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  • 1
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-01-08
    Description: This Special Issue provides an update on the state of the art and current trends in polymeric drug delivery systems specifically designed for improving drug bioavailability. The multiple contributions received further strengthen the role of polymers in modern drug delivery and targeting, illustrating the different approaches possible and unveiling what the future may bring.
    Keywords: Histoplasma capsulatum ; PLGA ; Itraconazole ; macrophage ; functionalized nanoparticle ; F4/80 receptor ; rutin ; nanocrystals ; anti-inflammatory ; hydroxypropyl beta-cyclodextrin ; nanoparticles ; budesonide ; chitosan ; colon delivery ; eudragit ; pellets ; ferrisilicate ; PEG ; insulin ; encapsulation ; diabetic mellitus ; polypeptides ; drug delivery ; doxorubicin ; cancer ; topology of poly-l-cystein ; antimicrobial ; antifouling ; pH sensitivity ; zwitterionic polymers ; gamma radiation ; copolyester ; SPION ; cysteine ; bioconjugation ; and enzymatic release ; polymeric nanoparticles ; drug delivery and targeting ; ocular posterior segment ; oxidative stress ; retinal degeneration ; nerve growth factor ; peanut agglutinin ; zebrafish ; molecular dynamics simulation ; interaction energy ; hydrogen bonding ; solid dispersion ; hot melt extrusion ; amorphous formulation ; tacrolimus ; sucrose acetate isobutyrate ; amorphous solid dispersion ; dissolution ; stability ; pharmacokinetics ; phytomedicine ; nanosponges ; lactoferrin ; bioavailability ; MDA-MB-231 cells ; caspase-3 ; cyclin-D1 ; dendrimers ; Janus nanoparticles ; biocompatibility ; nanoformulation ; pharmaceuticals ; 3D printing ; hybrid scaffold ; polycaprolactone ; vancomycin ; mesenchymal stem cells ; tissue engineering ; drug delivery systems (DDSs) ; osteomyelitis ; n/a ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PS Biology, life sciences ; bic Book Industry Communication::P Mathematics & science::PS Biology, life sciences::PSB Biochemistry
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  • 2
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-01-08
    Description: Lipid-based nanosystems, including solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), cationic lipid nanoparticles, nanoemulsions, and liposomes, have been extensively studied to improve drug delivery through different administration routes. The main advantages linked to these systems are the ability to protect, transport, and control the release of lipophilic and hydrophilic molecules (either small molecular weight or macromolecules); the use of generally recognized as safe (GRAS) excipients that minimize the toxicity of the formulations; and the possibility to modulate pharmacokinetics and enable the site-specific delivery of encapsulated payloads. In addition, the versatility of lipid-based nanosystems has been further demonstrated through the delivery of vaccines, protection of cosmetic actives, or improvement in the moisturizing properties of cosmetic formulations. Currently, lipid-based nanosystems are well established, and there are already different commercially approved formulations for different human disorders. This success has actually paved the way to diversifying the pipeline of development, upon addressing unmet medical needs for several indications, such as cancer; neurological disorders; and autoimmune, genetic, and infectious diseases. This Special Issue aims to update readers on the latest research on lipid-based nanosystems, both at the preclinical and clinical levels.
    Keywords: design of experiment ; porcine mucous membrane ; ophthalmic tissues ; permeation ; nanostructured lipid carriers ; gentiopicroside ; phospholipid complex ; self-nanoemulsion drug delivery system ; oral bioavailability ; pharmacokinetics ; antioxidants ; marine bio-waste ; bioactive compounds ; neurodegenerative diseases ; NLC ; solid lipid nanoparticles ; SLN ; intranasal administration ; nose-to-brain ; exosome ; drug loading ; exosomal delivery ; large-scale production ; lipid nanoparticles ; mucoadhesion ; ocular bioavailability ; surface modification ; liposomes ; baricitinib ; JAK-inhibitor ; transepidermal delivery ; skin permeation ; lipid NPs ; breast cancer ; siRNA delivery ; gene silencing ; personalized therapy ; bimatoprost ; central composite design ; glaucoma ; HET-CAM test ; solid lipid nanoparticles (SLNs) ; perillyl acid ; biodistribution ; empty lipid nanoparticles ; reactogenicity ; xenobiotics ; ionizable lipids ; isoniazid ; in vivo pharmacokinetics ; drug release profile ; histopathological toxicity ; mannosylation ; nanocarriers ; Chagas disease ; Trypanosoma cruzi ; in vivo assays ; quality by design ; plumbagin ; diabetes ; in vitro ; niosomes ; levosulpiride ; antidepressant ; acute toxicity ; in vivo imaging ; bioavailability ; cisplatin ; co-encapsulation ; mifepristone ; synergism ; gefitinib ; lipid ; surfactant ; stability ; breast cancer cell ; MTT assay ; anticancer ; n/a ; bic Book Industry Communication::T Technology, engineering, agriculture::TB Technology: general issues
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  • 3
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-04-05
    Description: Model-informed precision dosing (MIPD) is an advanced quantitative approach focusing on individualized treatment optimization. MIPD integrates mathematical models of drugs and diseases combined with individual patient characteristics (e.g., genotype, anthropometric factors, and organ function). MIPD has been highlighted as a useful tool for drug dosage selection in both the drug development process and clinical practice and it is a rapidly growing discipline that is supported by the main drug regulatory agencies. Despite the potential benefits of this methodology toward personalized medicine, its application is still limited. The Special Issue presented here includes several PKPD and PBPK models focused on improving the current state of art regarding the PK behaviour of different drugs with the aim of improving the efficacy/safety balance of these treatments and their clinical outcome; the Special Issue is intended to be of particular interest for clinical pharmacologists, pharmacometricians, and specific clinicians who routinely use the considered drugs.
    Keywords: model-informed precision dosing (MIPD) ; efficacy PKPD indexes ; pharmacokinetics ; pharmacodynamics ; PKPD modeling and simulation ; dosing algorithms ; nomograms ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KND Manufacturing industries::KNDP Pharmaceutical industries
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  • 4
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-03-28
    Description: Nowadays, diet-related non-communicable diseases and their complications are one of the most important public health problems worldwide. Food supplements and functional foods are considered food products which contribute to the achievement of optimal nutritional well-being, health status, and quality of life through reducing the risk of diseases and promoting the appropriate function of human organs and systems. Nowadays, the assessment of these functional foods and the study of their implications in nutrition and health are important challenges in societies of developed countries where consumers increasingly demand foods with added value beyond the provision of nutrients and the satisfaction of appetite. In this reprint, the characterization of the nutritional composition and phytochemicals of functional foods and food supplements as well as the evaluation of their potential health benefits in different disorders and diseases through clinical trials or preliminary studies are addressed.
    Keywords: food supplement ; folic acid ; pregnancy ; food safety ; health claims ; nutrition ; Amazonian fruits ; composition ; metabolic effects ; royal jelly ; acetylcholine ; fatty acid ; ophthalmology ; dry eye ; magnesium ; pharmacy ; food supplements ; drugstore ; functional foods ; healthy eating ; credibility ; extrinsic attributes ; conjoint analysis ; Mediterranean diet ; phytonutrients ; dietary recommendations ; healthy diet ; polyphenols ; flavonoids ; carotenoids ; organosulfur ; caffeine ; antidiabetic activity ; antioxidant activity ; inhibition of α-glucosidase ; inhibition of α-amylase ; inhibition of collagenase ; kombucha ; bacteria ; yeast ; metagenome ; metabolome ; tea polyphenols ; antioxidants ; Glossogyne tenuifolia ; exercise ; forelimb grip strength ; lactate ; ammonia ; creatine kinase ; medium-chain triglycerides (MCTs) ; obesity ; energy expenditure ; diet-derived fat ; postprandial resting metabolism ; sedentary ; octanoic acid ; decanoic acid ; creatine ; magnetic resonance spectroscopy ; cost-effectiveness ; brain ; muscle ; healthcare ; anthocyanins ; organosulfur compounds ; tannins ; phenolic acids ; Persea americana ; non-alcoholic liver disease ; liver enzymes ; inflammation ; oxidative stress ; novel foods ; novel ingredients ; extracts ; risk assessment ; dietary supplements ; HPLC ; food authenticity ; neural tube defects ; food ; food analysis ; food ingredients ; infant formula ; kynurenic acid ; (poly)phenol-based supplement ; pharmacokinetics ; urinary excretion ; bioavailability ; inter-individual variability ; non-invasive brain stimulation ; TMS ; a-tDCS ; indicaxanthin ; brain food ; cortical excitability ; homeostatic plasticity ; trans-resveratrol ; regulation ; labels ; nutrition claims ; high-performance thin-layer chromatography ; HPTLC ; glutamine ; intestinal stem cells ; crypt ; proliferation ; burns ; micronutrient ; health claim ; labeling ; European legislation ; thema EDItEUR::G Reference, Information and Interdisciplinary subjects::GP Research and information: general ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences ; thema EDItEUR::J Society and Social Sciences::JB Society and culture: general::JBC Cultural and media studies::JBCC Cultural studies::JBCC4 Cultural studies: food and society
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  • 5
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-04-05
    Description: This Special Issue is a collection of research topics on developing analytical and bioanalytical methods for isolation, identification, and determination of substances in biomedical and pharmaceutical matrices. Special attention is given to advancements in sample preparation, separation techniques and novel detection methods of small molecules, peptides, and monoclonal antibodies. The presented analytical methods exhibit several applications, including pharmacokinetic studies, therapeutic drug monitoring, microdialysis, toxicology, disease screening or drug stability study. Two comprehensive review articles were also presented on applying capillary electrophoresis to analyze bioactive compounds in herbal matrices.
    Keywords: CNS ; sulfasalazine ; brain to plasma ratio ; LC-ESI-TOF-MS ; rituximab ; quadripolar mass spectrometer ; albumin depletion ; pharmacokinetics ; orbitrap mass spectrometer ; IgG-immunocapture ; bubble-generating magnetic liposomes ; bionic membrane ; permeable compounds ; herbal medicines ; LC–MS ; capillary electrophoresis ; herbal ; raw material ; tea ; polyphenols ; flavonoids ; amino acids ; coumarins ; alkaloids ; chlorambucil and valproic acid ; HPLC-UV and GC-MS methods ; optimization and validation ; determination in plasma ; combined anticancer therapy ; herbal drugs ; medicinal plants ; quality control ; quantitative analysis ; pharmaceutical analysis ; 4-acetamidobenzoic acid ; validation ; pharmacokinetic ; pigs ; LC-MS/MS ; iron determination ; spectrophotometry ; flow analysis ; direct injection detector ; multi-pumping flow system ; medical errors ; hospital workflow ; patient safety ; Raman spectroscopy ; IV drugs ; piperacillin ; tazobactam ; non-invasively ; vildagliptin ; remogliflozin ; ratio derivative spectrophotometry ; determination ; formulation ; ecofriendly ; confidence interval ; stability ; retrospective analysis ; sample size ; regulatory bioanalysis ; bioanalytical method validation ; heparin ; metal–organic framework ; zeolite imidazolate framework-8 ; kinetic ; thermodynamic ; Oncheong-eum ; traditional herbal prescription ; method development ; method validation ; high-performance liquid chromatography ; thalassemia ; human hemoglobin ; wooden-tip electrospray ionization ; multiply charged ions ; mass spectrometry ; multiply charged ion ; GC–MS ; analytical QbD ; genotoxic impurity ; alkyl halide ; (Q)SAR ; analytical method development ; tyrosine kinase inhibitor ; liquid chromatography–mass spectrometry ; active metabolite ; therapeutic drug monitoring ; chronic lymphocytic leukemia ; assay error equation ; oral anticancer drug ; IWR-1-endo ; Wnt signaling inhibitor ; solid-phase extraction ; cerebral microdialysis ; bioanalysis ; Tafamidis ; polymorphs ; crystal structure ; powder diffraction ; thermal stability ; blood collection tubes ; citrate anticoagulant ; direct spectrometric determination ; quality control method ; anticoagulant concentration ; draw volume ; anticoagulant volume ; magnesium contamination ; potassium contamination ; Agrimonia pilosa ; apigenin-7-O-glucuronide ; cream ; HPLC-DAD ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PN Chemistry ; bic Book Industry Communication::P Mathematics & science::PN Chemistry::PNF Analytical chemistry
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  • 6
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-03-28
    Description: This Special Issue published one editorial, eight articles and four reviews from approximately one hundred authors. It aimed to provide cutting-edge research on pre-clinical development and the clinical translation of radiopharmaceuticals within the molecular imaging community. The Special Issue covered radioligand development, existing radiotracer optimization, imaging agent evaluation in animal models, the clinical production of radiopharmaceuticals, and investigative research on the use of molecular imaging probes in human subjects. We appreciate all the authors’ significant contributions to this Special Issue and hope the readers will enjoy the content.
    Keywords: nanoparticle ; multimodal imaging ; photoacoustic ; heterobivalent peptide ; Alzheimer’s disease ; amyloid-beta ; animal model ; astrocyte ; blood–brain barrier ; imaging ; metabolism ; microglia ; neuroinflammation ; neurotransmitter receptors ; positron emission tomography ; synaptic density ; vascular imaging ; FDG ; PET/CT ; microvasculature imaging ; ABC-transporter ; drug-induced liver injury ; hepatotoxicity ; organic anion-transporting polypeptide ; pharmacokinetics ; liver function ; SLC-transporter ; V/Q PET/CT ; [68Ga]Ga-MAA ; 68Ga-labelled carbon nanoparticles ; glioblastoma ; fluorescence guided surgery ; 5-ALA ; fluorescein ; NIR-AZA ; magnetic resonance imaging ; high resolution ; hybrid imaging ; psychiatric disorders ; extracellular vesicles (EVs) ; umbilical cord mesenchymal stem cell (UCMSC) ; diabetes ; I-124 ; positron emission tomography (PET) ; intravenous (I.V.) administration ; intra-arterial (I.A.) administration ; biodistribution ; fluorine-18 ; PET ; oxime ; PSMA ; lipophilicity ; radiometals ; copper-61 ; liquid targets ; post-processing ; [61Cu]Cu-DOTA-NOC ; [61Cu]Cu-DOTA-TOC ; [61Cu]Cu-DOTA-TATE ; FAP ; 99mTc-FAP inhibitor ; 99mTc-labeled iFAP ; tumor microenvironment ; SPECT ; GluN1/2B receptors ; NMDA ; [3H]ifenprodil ; σ1 and σ2 receptors ; receptor occupancy ; PET imaging ; drug development ; neurodegenerative diseases ; n/a ; thema EDItEUR::G Reference, Information and Interdisciplinary subjects::GP Research and information: general ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences
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  • 7
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-02-02
    Description: This reprint covers a wide range of topics including, but not limited to, new analytical and bioanalytical methods relevant to the separation, identification, and determination of substances in pharmaceutics, pharmacokinetics, nanobiotechnology, clinical chemistry, and related disciplines; methods for the identification of bioactive compounds in functional foods and medicinal plants; applications of chromatography and allied techniques in biomedical sciences.
    Keywords: wild rice ; antioxidant ; macroporous resins ; LC-MS/MS ; phenolics ; procyanidins ; osimertinib ; UPLC-TOF-MS ; rat ; pharmacokinetics ; carbonyl derivatization ; phenylhydrazine ; phenylenediamine ; hydroxylamine ; water analysis ; lipoxidation ; lisdexamfetamine dimesylate ; impurities ; structural elucidation ; forced degradation ; HPLC validation ; chemical constituent profiles of Sinisan ; chinese medicine processing ; chinese medicinal formula compatibility ; Dendropanax morbifera leaf ; xanthine oxidase ; hyperuricemia ; HPLC ; advanced glycation end-products (AGEs) ; Nε-(carboxymethyl) lysine (CML) ; Nε-(carboxyethyl) lysine (CEL) ; antler velvet processing ; UPLC-MS/MS ; Cinnamomum yabunikkei leaf ; elastase ; Citrus junos Seib ex TANAKA ; rhKGF-1 ; rhKGF-2 ; bioactivity ; cell-based bioassay ; method validation ; CYP450 enzyme ; cocktail probe drug ; RT-PCR ; galangin ; affecting factors ; amadori compound ; furosine ; Maillard reaction ; velvet antler processing ; Brazilian green propolis ; phenolic acids ; UPLC-ESI-QTOF-MS ; quantitation ; methodological verification ; Glycyrrhizae Radix extract ; glycyrrhizin ; isoliquiritigenin ; liquiritigenin ; liquiritin ; LC–MS/MS analysis ; desoxo-narchinol A ; Nardostachys jatamansi ; bioavailability ; silybin ; silymarin product ; comparative pharmacokinetics ; ginsenosides ; red ginseng extract ; human ; acanthus ilicifolius herb ; phenylethanoid glycosides ; C.tricuspidata Bureau ; tyrosinase ; dialyzable leukocyte extract ; Transferon® ; complex mixture of peptides ; quality specifications ; biological potency ; development and validation ; Dioscorea nipponica Makino ; steroidal saponin ; HPLC-UV ; UPLC-QTOF/MS ; validation ; osteosarcoma ; apoptosis ; epinastine ; comparison ; SH-1242 ; 2-(3,4-dimethoxyphenyl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-6-yl)ethanone ; HPLC-MS/MS ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PN Chemistry ; bic Book Industry Communication::P Mathematics & science::PN Chemistry::PNF Analytical chemistry
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  • 8
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-04-05
    Description: This reprint is an excellent collection of articles that deal with difficult-to-treat infections in the ICU environment. Multiresistant bacteria and fungi create severe treatment problems to the physician charged with their care. We hope that this book will help everyday dilemmas and add useful information on difficult topics.
    Keywords: Acinetobacter ; pandrug-resistant ; antimicrobial combinations ; synergy ; renal replacement therapy ; Monte Carlo simulation ; antibiotics ; pharmacokinetics ; pharmacodynamics ; microbiome ; probiotics ; intensive care unit ; dysbiosis ; ventilator-associated pneumonia ; extracorporeal membrane oxygenation ; ECMO ; critical illness ; antibiotic choices ; HAP ; VAP ; colonization ; antibiotic pressure ; bloodstream infection ; bacteraemia ; sepsis ; septic shock ; empirical ; probabilistic antibiotics ; source control ; de-escalation ; ICU ; intensive care ; antimicrobial stewardship ; COVID-19 ; procalcitonin ; C-reactive protein ; presepsin ; infection ; biomarker ; guided antimicrobial therapy ; APACHE II score ; bacteremia ; broth microdilution ; colistin ; colistin-resistant ; Gram-negative ; mortality ; SOFA score ; candidemia ; incidence ; epidemiology ; Candida species ; non-albicans Candida species ; fluconazole resistance ; critically ill ; beta-lactam antibiotics ; Acinetobacter baumannii ; antibiotic optimisation ; antibiotic stewardship (AMS) ; aspiration pneumonia ; hospital-acquired pneumonia (HAP) ; multidrug-resistance (MDR) ; non-fermentative Gram-negative bacilli (GNB) ; polymicrobial ; pneumonia resolution ; ventilator-associated pneumonia (VAP) ; carbapenem-resistant A. baumannii (CRAb) ; infection control ; antimicrobial agents ; carbapenems ; antibiotic resistance ; clinical pharmacy services ; Klebsiella pneumoniae ; Pseudomonas aeruginosa ; salvage treatment ; double carbapenem ; newer β-lactam-β-lactamase inhibitors ; cefiderocol ; eravacycline ; SARS-CoV-2 infection ; mechanical ventilation ; risk factors ; blood stream infection ; defined daily dose ; antibiotics utilization ; empiric ; n/a ; bic Book Industry Communication::M Medicine
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  • 9
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-02-02
    Description: Advanced Blood-Brain Barrier Drug Delivery is a reprint with a summary editorial, followed by 16 chapters that cover five areas of brain drug delivery, including receptor-mediated transport (RMT), carrier-mediated transport (CMT), active efflux transport (AET), Trojan horse lipid nanoparticles (LNP), and in vivo methods for measurement of drug transport across the blood–brain barrier (BBB).
    Keywords: blood–brain barrier (BBB) ; brain drug delivery ; prodrugs ; solute carriers (SLCs) ; lysosomal storage disease ; neuronopathic mucopolysaccharidosis ; blood–brain barrier ; neurodegeneration ; enzyme replacement therapy ; receptor-mediated transcytosis ; transferrin receptor ; insulin receptor ; endothelium ; receptor-mediated transport ; carrier-mediated transport ; genetic engineering ; IgG fusion proteins ; nanoparticles ; liposomes ; TrkB ; agonist antibody ; variable new antigen receptor (VNAR) ; neuroprotection ; transferrin receptor 1 (TfR1) ; blood-brain barrier (BBB) ; 6-OHDA ; Parkinson’s disease ; bispecific antibody ; alpha-synuclein (αSYN) ; Parkinson’s disease (PD) ; immunotherapy ; monoclonal antibody ; transferrin receptor (TfR) ; receptor-mediated transcytosis (RMT) ; single domains antibody ; IGF1R ; neurotensin ; protein-based therapy ; lysosomal storage disorders ; fusion proteins ; Alzheimer’s disease ; neurotrophic factors ; decoy receptors ; ATP-binding cassette transporters ; drug delivery ; ischemic stroke ; SLC transporters ; lipid nanoparticle ; ssPalm ; mRNA transfection ; hCMEC/D3 cells ; cell toxicity ; SWATH-MS ; translation ; chaperonin-containing TCP-1 ; proton-coupled organic cation antiporter ; photo-affinity labeling ; proteomics ; SWATH-MS (sequential window acquisition of all theoretical-mass spectra) ; pharmacokinetics ; compartmental models ; physiologically based PK models ; blood-brain barrier ; antibody ; cavernous sinus ; BBB–peptide shuttle ; brain delivery ; solute carrier (SLC) transporters ; amyotrophic lateral sclerosis (ALS) ; NSC-34 cell lines ; taurine transporter (Taut) ; large amino acid transporter 1 (LAT1) ; monocarboxylate transporters (MCTs) ; organic cation transporters (OCTNs) ; choline transporter-like protein-1 (CTL1) ; TNF-α inhibitor ; molecular Trojan horse ; endosomal ; liposome ; nanoparticle ; targeting ; transferrin ; n/a ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::M Medicine::MM Other branches of medicine::MMG Pharmacology
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  • 10
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-11-30
    Description: Research in ophthalmic drug delivery has developed significant advances in the few last years, and efforts have been made to develop more effective topical formulations to increase drug bioavailability, efficiency, and safety. Drug delivery to the posterior segment of the eye remains a great challenge in the pharmaceutical industry due to the complexity and particularity of the eye's anatomy and physiology. Some advances have been made with the purpose of maintaining constant drug levels in the site of action. The anatomical ocular barriers have a great impact on drug pharmacokinetics and, subsequently, on the pharmacological effect.Despite the increasing interest in efficiently reaching the posterior segment of the eye with reduced adverse effects, there is still a need to expand the knowledge of ocular pharmacokinetics that allow the development of safer and more innovative drug delivery systems. These novel approaches may greatly improve the lives of patients with ocular pathologies.
    Keywords: ocular ; drug delivery ; pharmacokinetics ; tissue isolation ; rat ; eye ; drug concentration ; method ; pigment ; melanin ; aniridia ; ataluren ; ophthalmic solution ; rare disease ; stability ; tacrolimus ; hydroxypropyl-β-cyclodextrin ; topical ophthalmic administration ; eye drops ; uveitis ; PET/CT imaging ; ocular implants ; electrospinning technique ; glaucoma ; sustained drug release ; poly ε-caprolactone ; electrospun fibers ; permeability ; retina ; retinal pigment epithelium ; Ussing chamber ; intravitreal half-life ; posterior capsule opacification ; pathophysiology ; wound healing ; lens epithelial cells ; intraocular lenses ; experimental models ; clinical studies ; gold nanoparticles ; anterior chamber ; distribution ; intracameral injection ; trabecular meshwork ; hyaluronic acid ; liposomes ; intravitreal ; ocular drug delivery ; retinal explants ; amantadine ; blood–retinal barrier ; retinal disease ; NMDA receptor ; inner BRB ; retinal capitally endothelial cells ; outer BRB ; retinal pigment epithelial cells ; transporter ; rivoceranib ; drug repositioning ; microsphere ; subfoveal choroidal neovascularization ; macular degeneration ; endotoxin-induced uveitis ; interleukins ; immunosuppressants ; physicochemical stability ; container-content interaction ; leachable compound ; nanoparticles ; PLGA ; lactoferrin ; nanoprecipitation ; protein nanocarriers ; keratoconus ; corneal ecstatic disorder ; posterior capsular opacification ; intraocular lens ; surface modification ; photothermal therapy ; photodynamic therapy ; micro-pattern ; anti-biofouling ; ocular hypertension ; prostaglandin analogues ; aqueous solubility ; chemical stability ; intraocular pressure ; cystinosis ; ophthalmic administration ; cysteamine ; compounded formulation ; PET ; nanocrystals ; conjunctivitis ; besifloxacin ; Povacoat® ; fluoroquinolones ; acanthamoeba keratitis ; controlled drug delivery ; contact lens ; miltefosine ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KND Manufacturing industries::KNDP Pharmaceutical industries
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  • 11
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-11-30
    Description: In this Special Issue, our aim was to collect studies on clinical pharmacology and pharmacy of antimicrobial agents from both human and veterinary medicine as the complex problem of AMR requires actions taken within the One Health approach that involve both fields. Studies covered here are about new or optimized usage of already authorized antimicrobials, as well as discoveries about new agents, new combinations of drugs, and drug repositioning. Pharmacodynamic, pharmacokinetic, and toxicological aspects of individual and combinational drug use are areas covered in this Special Issue.
    Keywords: antibiotic combination ; minimum inhibitory concentration ; Monte Carlo ; synergistic effect ; antibiotics ; combination therapy ; multi-drug resistant infection ; meta-analysis ; pan-genome ; Campylobacter ureolyticus ; UDP-3-O-acyl-N-acetylglucosamine deacetylase ; LpxC ; campylobacteriosis ; self-medication ; students ; habits ; cystic fibrosis ; P. aeruginosa ; transporters ; Escherichia coli ; suture ; antimicrobial ; pharmacodynamics ; triclosan ; surgical site infection ; time-kill ; contact killing ; translational modelling ; antifungals ; adverse drug reaction (ADR) ; drug-drug interaction (DDI) ; polypharmacy ; multimorbidity ; intensive care patients ; traumatology ; elderly patients ; organ failure ; multi-organ failure ; drug safety ; patient safety ; nonlinear mixed-effects modeling ; glomerular filtration rate ; dosing regimen ; oxacillin ; Monte Carlo simulations ; adsorption ; desorption ; doxycycline ; pH dependence ; small ruminant feed ; heterocyclic compounds ; phenolic compounds ; pyran ; food microbiology ; microbial pathogen ; serum/plasma concentrations ; interstitial concentrations ; tissue concentrations ; pharmacokinetics ; macrolide antibiotics ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::M Medicine::MM Other branches of medicine::MMG Pharmacology
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  • 12
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-09-11
    Keywords: drug design and discovery ; drug&ndash ; protein interactions ; drug response ; drug solubility ; antimicrobial drugs ; antiviral drugs ; antibiotics ; anticancer drugs ; cancer prevention ; molecular modeling ; molecular mechanisms ; crystallography ; preclinical study ; pharmacokinetics ; pharmacodynamics ; pharmacognosy ; nuclear receptors ; receptor agonist and antagonist ; activity profiling, markers and diagnostics ; drug carriers ; dosage form ; nanoparticles ; dissolution testing ; bic Book Industry Communication::M Medicine::MB Medicine: general issues::MBG Medical equipment & techniques
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  • 13
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-04-05
    Description: Novel Anticancer Strategies reviews important findings and updates within the cancer therapy field, of great interest to those in academic research studying the development and validation of novel anticancer approaches. The Editor invited preeminent specialists to contribute to original and review articles devoted to key areas of major progress and expectations. Key features: Nanoparticle-based drug delivery in cancer therapy; Extracellular vesicles for anticancer drug delivery; Peptide-based drug conjugates; Cancer stem cells as a valuable target to eradicate tumor relapse; Spheroids in preclinical model for cancer research; and cancer immunotherapy.
    Keywords: tumor-homing extracellular vesicles ; pH-sensitive extracellular vesicles ; doxorubicin ; tumor therapy ; pancreatic cancer ; targeted tumor therapy ; homing peptide ; antitumor peptide conjugates ; daunomycin ; oxime linkage ; combinatorial immunotherapy ; cytotoxics ; biomarkers ; precision medicine ; immunotherapy ; anti-PD-L1 ; ionizing irradiation ; pharmacokinetics ; tumor-immune interaction ; global sensitivity ; immuno-oncology ; mathematical modeling ; glycol chitosan nanoparticle ; high-intensity focused ultrasound ; deep tumor penetration ; dense ECM ; cancer treatment ; prostate cancer ; gastrin-releasing peptide receptor ; RM26 ; albumin-binding domain ; targeted therapy ; gastrin-releasing peptide receptors (GRPR) antagonist ; cervical cancer ; tetraarsenic hexoxide ; patient-derived xenograft ; autophagy ; cisplatin ; fenbendazole ; micelle solubilization ; Soluplus® polymeric micelles ; toxicity test ; sonoporation ; microbubbles ; ultrasound ; intracellular signaling ; phosphorylation ; ultrasound contrast agents ; drug delivery ; cellular stress ; tumour microenvironment ; cancer stem cells ; extracellular vesicles ; drug delivery systems ; liposomes ; immunoliposomes ; antisense oligonucleotides ; 3D cultures ; tumor microenvironment ; tumor spheroids ; efficacy analysis ; drug resistance ; cancer therapy ; glioblastoma ; receptor tyrosine kinases ; epidermal growth factor receptor ; small molecule inhibitors ; nanoformulations ; breast cancer ; micelles ; dendrimers ; anticancer drugs ; platinum drug ; methotrexate ; lung metastasis ; liver metastasis ; cancer treatments and progression biomarkers ; mesoporous silica nanoparticles ; controlled release ; anticancer natural prodrugs ; natural products ; cancer targeting ; nanoformulations/nanomedicine applications ; n/a ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::M Medicine::MJ Clinical & internal medicine::MJC Diseases & disorders::MJCL Oncology
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  • 14
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-03-31
    Description: Recently, microfluidic, nanofluidic and lab-on-a-chip devices have gained particular attention in biomedical applications. Due to their advantages, such as miniaturization, versatility, ease of use, cost-effectiveness, and the potential to replace animal models for drug development and testing, these devices hold tremendous potential to revolutionize the research of more effective treatments for several diseases that threaten human life. With integrated biosensors, these devices allow the development and design of micro- and nanoparticles to be studied in detail, modelling human physiology, investigating the molecular and cellular mechanisms underlying disease formation and progression, and gaining insights into the performance and long-term effects of responsive drug delivery nanocarriers. This Special Issue gathered research papers, and review articles focusing on novel microfluidic, nanofluidic and lab-on-a-chip devices for biomedical applications, addressing all steps related to fabrication, biosensor integration and development, characterization, numerical simulations and validation of the devices, optimization and, the translation of these devices from research labs to industry settings.
    Keywords: protein biomarker ; microarray ; microfluidic cassette ; multiplex measurement ; immunoassay ; point-of-care testing ; microfluidic device ; small intestine ; ex vivo ; histology ; embedded resin ; sectioning ; peptide biosensor ; lab-on-a-chip ; label-free detection ; peptide aptamers ; protein biomarkers ; microfluidic biochip ; troponin T ; computational simulations ; drug discovery ; organ-on-a-chip ; microfluidic devices ; preclinical models ; numerical simulations ; automation ; non-enzymatic ; DNA amplification ; L-DNA ; microfluidic ; fluorescence ; paper microfluidics ; sweat ; sensing ; hydrogels ; lactate ; osmotic pumping ; evaporation ; capillary ; wicking ; biochemical assay ; microfluidics ; cell trap ; RBC ; evolutionary algorithm ; generative design ; artificial intelligence ; organ-on-chip ; liver-on-chip ; liver disease ; multi-level microfluidic device ; live cell imaging ; long-term microscopy imaging ; focus drifting ; immersion oil viscosity ; bacterial population dynamics ; single-cell studies ; E. coli ; mother machine ; computational fluid dynamics ; cancer-on-chip ; xenograft ; colorectal cancer ; pharmacodynamics ; pharmacokinetics ; drug efficacy ; oxaliplatin ; microfabrication ; microphysiological system ; biophysical stimuli ; biochemical stimuli ; in vitro cell culture ; cortical neurons ; hippocampal neurons ; electrical stimulation ; Micro-Electrode Arrays ; engineered neuronal networks ; polydimethylsiloxane ; microchannels ; in vivo micro bioreactor ; additive manufacturing ; poly-(ethylene glycol)-diacrylate ; biocompatibility ; COVID-19 ; diagnosis ; image analysis ; PCR ; SARS-CoV-2 ; n/a ; thema EDItEUR::M Medicine and Nursing
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  • 15
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-09-11
    Description: It has been known that cellular glutathione content and its speciation play a role, among others, in redox homeostasis, cell cycle control, immunological defense, and pathological abnormalities. Furthermore, it plays a significant role in the biotransformation of drugs and other endogenous or exogenous electrophilic species. Most of these cellular functions are related to the thiol function of the cysteine moiety.This reprint presents the publications that appeared in the Special Issue of Molecules, “Glutathione: Chemistry and Biochemistry.” The first three contributions review the present-day knowledge of the GSH/GSSG system and the most important GSH-related proteins involved in regulating various cellular events. The subsequent four contributions present selected interventions that modulate the GSSG/2GSH system. One of the contributions to this session describes a new HPLC method to quantify the reduced and oxidized glutathione levels. The third session involves three contributions demonstrating the role of GSH in the metabolism of different candidate and clinically used anticancer drugs. One of the contributions, a theoretical work, provides helpful information for developing GSH analogs with high ACE inhibitor activity.By purpose and content, this Special Issue is addressed to the vast number of life science researchers (academic and industrial) and medical professionals who are interested in or already engaged in research that involves glutathione.
    Keywords: cyclophosphamide ; autoimmune diseases ; glutathione ; glutathione-S-transferase ; polymorphism ; glutaredoxin ; iron-sulfur cluster ; iron ; S-glutathionylation ; S-nitrosylation ; GSH ; nitrosoglutathione ; redox-regulation ; polymerized whey protein ; physicochemical properties ; pharmacokinetics ; toxicity ; chalcone ; cysteine ; thiols ; Michael addition ; diastereoselective addition ; reactive oxygen species ; oxidative stress ; nanotoxicity ; cell injury ; fluorescence probes ; brain ; liquid chromatography ; diode array detector ; anticancer drugs ; mechanisms of glutathione conjugation reaction ; detoxification ; bioactivation ; sulodexide ; endothelial cells ; ischemia ; apoptosis ; GSSG ; GCLc ; GSS ; redox potential ; supramolecular arrangement ; M06-2X/6-311++G(d,p) ; DFT ; molecular docking ; angiotensin-converting enzyme ; cell ; redox homeostasis ; glutathionylation ; glutathione system ; glutathione enzyme ; n/a ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PS Biology, life sciences
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  • 16
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-09-11
    Keywords: iron oxide magnetic nanoparticles ; silica coating ; magnetic hyperthermia ; cancer cells ; alamar blue ; neutral red ; A549 ; A35 ; BJ ; ultrasmall magnetic iron oxide nanoparticles ; inflammatory pain ; analgesia ; pro-inflammatory cytokines ; neurotoxicity ; long-term potentiation ; solid lipid nanoparticles ; magnetic nanoparticles ; magnetic solid lipid nanoparticles ; cancer theranostics ; MRI-contrast agents ; pulsed laser ablation in liquids ; multimodal imaging ; MRI ; CT ; photothermal therapy ; iron-gold nanoparticles ; pharmacokinetics ; magnetic targeting ; micro-systems ; nano-systems ; drug delivery ; nanoparticles ; microparticles ; targeted delivery ; magnetic guidance ; theranostics ; imaging ; AC biosuceptometry ; cirrhosis-associated rat hepatocarcinogenesis ; nanotechnology ; magnetoresponsive nanocomposite ; functional coating ; particle targeting ; particle aggregation ; stent targeting ; nanomedicine ; MRI technology ; patient-centred healthcare ; iron oxide nanoparticles ; paramagnetic salinomycin complexes ; bacterial ghosts ; gadolinium ; manganese ; lectin ; PLGA ; ConA ; magnetic polymer nanoparticles ; MPQ ; allografts ; photodynamic therapy ; IR775 ; image-guided therapy ; n/a ; bic Book Industry Communication::T Technology, engineering, agriculture::TB Technology: general issues
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  • 17
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2022-05-06
    Description: The gastrointestinal tract (GIT) can be broadly divided into several regions: the stomach, the small intestine (which is subdivided to duodenum, jejunum, and ileum), and the colon. The conditions and environment in each of these segments, and even within the segment, are dependent on many factors, e.g., the surrounding pH, fluid composition, transporters expression, metabolic enzymes activity, tight junction resistance, different morphology along the GIT, variable intestinal mucosal cell differentiation, changes in drug concentration (in cases of carrier-mediated transport), thickness and types of mucus, and resident microflora. Each of these variables, alone or in combination with others, can fundamentally alter the solubility/dissolution, the intestinal permeability, and the overall absorption of various drugs. This is the underlying mechanistic basis of regional-dependent intestinal drug absorption, which has led to many attempts to deliver drugs to specific regions throughout the GIT, aiming to optimize drug absorption, bioavailability, pharmacokinetics, and/or pharmacodynamics. In the book "Regional Intestinal Drug Absorption: Biopharmaceutics and Drug Formulation" we aim to highlight the current progress and to provide an overview of the latest developments in the field of regional-dependent intestinal drug absorption and delivery, as well as pointing out the unmet needs of the field.
    Keywords: bioequivalence ; Biopharmaceutics Classification System ; in vitro ; dissolution test ; pravastatin ; oral absorption ; in silico modeling ; GastroPlus ; Phoenix WinNonlin ; pharmacokinetics ; clinical studies ; ibuprofen ; manometry ; gastrointestinal ; mechanistic modeling ; PBPK ; PBBM ; disintegration ; dissolution ; enteric-coated ; ICH ; quality control ; regional intestinal permeability ; permeation enhancers ; absorption-modifying excipients ; oral peptide delivery ; intestinal perfusion ; pharmaceutical development ; controlled release drug product ; biopharmaceutics classification system ; drug solubility ; drug permeability ; location-dependent absorption ; segregated flow intestinal model (SFM) ; traditional model (TM) ; route-dependent intestinal metabolism ; first-pass effect ; drug-drug interactions ; DDI ; in vitro in vivo extrapolations ; IVIVE ; zero-order absorption ; first-order absorption ; combined zero- and first-order absorption ; transit compartment absorption model ; in situ perfusion ; microdevices ; shape ; mucoadhesion ; colon absorption ; nutrient digestion ; nutrient absorption ; gastrointestinal hormone ; postprandial glycaemia ; energy intake ; region of the gut ; obesity ; type 2 diabetes ; Franz–PAMPA ; BCS drugs ; biomimetic membrane ; Franz cell ; passive drug transport ; BCS class IV drugs ; segmental-dependent intestinal permeability ; intestinal absorption ; oral drug delivery ; biopharmaceutics ; physiologically-based pharmacokinetic (PBPK) modeling ; furosemide ; intestinal permeability ; human colon carcinoma cell layer (Caco-2) ; hierarchical support vector regression (HSVR) ; drug absorption ; drug solubility/dissolution ; regional/segmental-dependent permeability and absorption ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KND Manufacturing industries::KNDP Pharmaceutical industries
    Language: English
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  • 18
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2022-03-21
    Description: This book is a compendium of scientific articles submitted to a Special Issue of International Journal of Molecular Sciences, fostered by MDPI and curated by Dr. Annamaria Sandomenico and Dr. Menotti Ruvo from the Institute of Biostructure and Bioimaging of the National Research Council. All articles underwent a rigorous peer review and were selected to highlight the properties that make monoclonal antibodies and their functional fragments some of the most useful and versatile assets in therapy and diagnosis.
    Keywords: porcine deltacoronavirus ; nucleocapsid ; monoclonal antibodies ; neurodegenerative disorders ; affibody molecules ; blood–brain barrier ; receptor-mediated transcytosis ; transferrin receptor ; AL amyloidosis ; CD38 ; anti-CD38 MoAb ; Daratumumab ; Isatuximab ; myeloma ; BCMA ; bispecific T-cell engager ; antibody-drug conjugates ; chimeric antigen receptor T-cells ; belantamab mafodotin ; idecabtagene vicleucel ; JNJ-68284528 ; Mabs ; Antibody-Drug Conjugate ; cancer therapy ; drug targeting ; payload ; cross-linking ; antibody fragment ; Fab ; scFv ; E. coli ; YKL-40 ; CHI3L1 ; monoclonal antibody ; phage display ; lung metastasis ; prostate-specific membrane antigen ; in vivo imaging ; prostate cancer ; glutamate carboxypeptidase II ; NAALADase ; immunization ; antibody ; protocol ; guinea pig ; cDNA ; chimeric antigen receptor (CAR T) ; universal CAR T ; modular CAR T ; universal immune receptor ; CAR adaptor ; adoptive immunotherapy ; split CAR ; bispecific ; polyspecificity ; pharmacokinetics ; solubility ; aggregation ; viscosity ; developability ; stability ; affinity ; specificity ; protein engineering ; self-association ; non-specific binding ; immunogenicity ; antibody fragments ; single chain ; amyloid ; oligomer ; neurotoxicity ; NUsc1 ; bic Book Industry Communication::T Technology, engineering, agriculture::TB Technology: general issues
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  • 19
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2022-06-21
    Description: Derivatization is one of the most widely used sample pretreatment techniques in Analytical Chemistry and Chemical Analysis. Reagent-based or reagent-less schemes offer improved detectability of target compounds, modification of the chromatographic properties and/or the stabilization of sensitive compounds until analysis. Either coupled with separation techniques or as a “stand alone” analytical procedure, derivatization offers endless possibilities in all aspects of analytical applications.
    Keywords: tyrosine kinase inhibitors ; chloranilic acid ; charge-transfer reaction ; 96-microwell spectrophotometric assay ; high-throughput pharmaceutical analysis ; biogenic amines ; Lycium barbarum L. ; HPLC ; derivatization ; amino acids ; esterification ; GC–MS ; pentafluoropropionic anhydride ; stability ; toluene ; pigment ; linseed oil ; derivatisation ; quantification ; P/S ratio ; A/P ratio ; ∑D ; GC-MS ; ureide ; BSTFA ; creatine ; creatinine ; silylation ; TMS ; validation ; low-molecular-weight thiols ; human serum albumin ; α-lipoic acid ; blood plasma ; monobromobimane ; reduction ; sodium borohydride ; high-performance liquid chromatography ; fluorescence detection ; taurine ; glutamine ; clams ; high-resolution mass spectrometry ; nerve agents ; methylation ; chemical warfare agents ; sarin ; Novichoks ; 2-naphthalenethiol ; sulforaphane ; HPLC-UV/Vis ; pharmacokinetics ; acetonitrile-related adducts ; acetylenic lipids ; double and triple bond localization ; in-source derivatization ; mass spectrometry ; acetazolamide ; carbonic anhydrase ; enhancement ; inhibition ; pentafluorobenzyl bromide ; chiral metabolomics ; rice water ; d-amino acids ; enantiomer separation ; dimethyl labeling ; homocysteine thiolactone ; homocysteine ; zone fluidics ; o-phthalaldehyde ; fluorosurfactant-modified gold nanoparticles ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PN Chemistry ; bic Book Industry Communication::P Mathematics & science::PN Chemistry::PNF Analytical chemistry
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  • 20
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-03-27
    Description: This book covers the most recent research trends and applications of Pharmaceutical Analytical Chemistry. The included topics range from the adulteration of dietary supplements, to the determination of drugs in biological samples with the aim to investigate their pharmacokinetic properties.
    Keywords: growth hormone ; long-acting Fc-fusion recombinant human growth hormone ; method validation ; cell-based bioassay ; reporter gene assay ; pharmacokinetics ; tissue distribution ; alnustone ; rats ; LC-MS/MS ; inflammatory bowel disease ; fixed-dose combination ; biomimetic chromatography ; thiopurine immunosuppressants ; folic acid ; doxorubicin ; hernandezine ; pharmacokinetic study ; drug–drug interaction ; gardneramine ; monoterpenoid indole alkaloid ; memantine ; rimantadine ; amantadine ; zone fluidics ; o-phthalaldehyde ; derivatization ; stopped-flow ; quality control ; anwuligan ; rat ; optode ; polyhexamethylene biguanide hydrochloride ; lactone-rhodamine B ; contact-lens detergent ; dietary supplement ; adulteration ; low-field NMR ; multivariate analysis ; steroids ; Partial Least Squares regression ; in vitro permeability ; predictive model ; ketamine ; norketamine ; high throughput bar adsorptive microextraction ; LVI-GC-MS(SIM) ; urine ; baricitinib ; UPLC-MS/MS ; irbersartan ; n/a ; thema EDItEUR::G Reference, Information and Interdisciplinary subjects::GP Research and information: general
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  • 21
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-03-31
    Description: This book serves to highlight the pharmacokinetics/drug–drug interactions and mechanistic understanding in relation to the drug-metabolizing enzymes and drug transporters.This book presents a series of drug metabolism and transport mechanisms that govern the pharmacokinetic features of therapeutic drugs as well as natural herbal medicines. It also covers the pharmacokinetic interactions caused by inhibiting or inducing the metabolic or transport activities under disease states or the coadministration of potential inhibitors. It also deals with microenvironmental pharmacokinetic profiles as well as population pharmacokinetics, which gives new insights regarding the pharmacokinetic features with regard to drug metabolism and transporters.
    Keywords: tofacitinib ; dose-dependent pharmacokinetics ; hepatic and intestinal first-pass effect ; rats ; catalposide ; in vitro human metabolism ; UDP-glucuronosyltransferase ; sulfotransferase ; carboxylesterase ; celecoxib ; drug–drug interaction ; fluorescence ; HPLC ; metabolism ; repaglinide ; HSG4112 ; anti-obesity agent ; stereoselectivity ; pharmacokinetics ; compound K ; protopanaxadiol (PPD) ; biliary excretion ; intestinal metabolism ; Carthamus tinctorius extract ; notoginseng total saponins ; comparative pharmacokinetic study ; large volume direct injection ; compatibility mechanism ; mertansine ; human hepatocytes ; cytochrome P450 ; UDP-glucuronosyltransferases ; sodium-glucose cotransporter 2 (SGLT2) inhibitors ; DWP16001 ; kidney distribution ; inhibition mode ; diabetes ; transporter-enzyme interplay ; influx transporter ; efflux transporter ; physiologically based pharmacokinetic model ; cytochrome P450 enzymes ; tiropramide ; healthy Korean subjects ; modeling ; population pharmacokinetic ; quercetin ; breast cancer resistance protein ; inhibitor ; prazosin ; sulfasalazine ; kinetic analysis ; food–drug interactions ; Caco-2 ; EpiIntestinal ; first-pass ; P-gp ; BCRP ; drug transporter ; CYP3A4 ; oral availability ; automatization ; drug absorption ; drug dosing ; head-and-neck cancer ; real-time measurements ; taxanes ; tissue engineering ; UHPLC-MS/MS ; metformin ; verapamil ; drug interaction ; organic cation transporter 2 ; renal excretion ; acute renal failure ; gentamicin ; cisplatin ; hepatic CYP3A1(23) ; creatinine clearance ; renal clearance ; nonrenal clearance ; thema EDItEUR::M Medicine and Nursing ; thema EDItEUR::K Economics, Finance, Business and Management::KN Industry and industrial studies::KND Manufacturing industries
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  • 22
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2022-02-24
    Description: The book broadly deals with therapeutic monoclonal antibodies (mAbs) and various relevant topics, including different antibody formats such as Antibody–Drug Conjugates (ADC), bispecifics, nanoparticle-based mAbs and HER2+ cancers, immune checkpoint inhibitors and other closely related topics. Each paper was written by leading active research groups in their fields both from academia and industry. The book should be of interest to those scientists and researchers who develop or use biologics, biotherapeutics, biosimilars and biobetters in cancer treatment.
    Keywords: monoclonal antibody ; NSCLC ; immunotherapy ; ELISA ; pharmacokinetics ; pharmacogenetics ; anti-PD-1 monoclonal antibodies ; anti-acetylcholine receptor (AChR) antibody ; B cell ; immune checkpoint blockade ; immune-related adverse events (irAEs) ; myasthenia gravis (MG) ; non-small-cell lung cancer (NSCLC) ; nivolumab ; programmed cell death ligand 1 (PD-L1) ; T cell ; tetraspanins ; cancer ; Tspan8 ; radioimmunotherapy ; immune-checkpoint inhibitors ; LDH ; biomarkers ; Ang-2 ; antiangiogenic therapy ; in vivo imaging ; radio- and chemotherapy ; VEGF-A ; cancer therapy ; neovascularization ; angiogenesis ; tumor microenvironment ; colorectal cancer ; antibody ; NK cells ; ADCC ; CD133 ; prominin-1 ; gold nanoparticles ; antibody-drug conjugates ; cell penetrating peptide ; HIV-1 TAT ; active-targeting ; targeted delivery ; trastuzumab ; MMAE ; valine-citrulline ; affibody ; drug conjugates ; hepatic uptake ; DM1 ; dermatooncology ; immune checkpoints ; monoclonal antibodies ; passive immunotherapy ; canine B-cell lymphoma ; DLA-DR ; HLA-DR ; antibody-drug conjugate ; ADC ; methotrexate ; tumor immunity ; combination therapy ; multiple myeloma (MM) ; monoclonal antibodies (mAbs) ; antibody products ; B cell maturation antigens (BCMAs) ; bispecific T cell engagers (BiTEs®) ; checkpoint inhibitors 1 ; protein structure 2 ; pharmacokinetics 3 ; drug optimization 4 ; HER2-positive breast cancer ; metastatic disease ; neoadjuvant and adjuvant therapy ; targeted therapy ; acute myeloid leukemia ; CD123 ; IL3RA ; kinesin spindle protein inhibitor ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KND Manufacturing industries::KNDP Pharmaceutical industries
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  • 23
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2022-11-17
    Description: Caffeine is present in coffee and many other beverages and is the most widely used central nervous system stimulant. Coffee drinking or caffeine supplementation may have a role in preventing cardiometabolic and endocrine disease, neuroinflammation, cancer, and even all-cause mortality. Other aspects are either less known or controversial, including the effects on the brain–gut axis, neurodevelopment, behavior, pain, muscle–skeletal health, skin or sexual function. Studies focusing on special populations (neonates, children, adolescents, athletes, elderly, pregnant and nonpregnant women), or interactions with other drugs and foods, are relatively scarce but of obvious interest. Other compounds present in coffee and other caffeinated food stuffs may affect caffeine´s physiological effects with a tremendous impact on health. This Special Issue, which contains twenty-one manuscripts, has focused on some of these varied topics, providing further evidence of the multiple health benefits that coffee/caffeine intake may exert in humans, at least in specific populations (with a particular genetic profile or suffering from specific diseases). However, the specific effects in the different organs and systems, as well as the mechanisms involved are not yet clear. Furthermore, within the current context aiming to sustainable development, the coffee plant Coffee sp. and its so-far relatively neglected by-products are expected to become soon a source of ingredients for new functional foods whose properties will need to be precisely determined. We hope the readers of this Special Issue will find inspiration for new studies on the topic.
    Keywords: pharmacokinetics ; energy drink ; exercise ; elite athlete ; performance ; football ; RPE ; DOMS ; sport performance ; supplementation ; ergogenic aids ; consumer ; behavior ; perception ; coffee ; health ; consumption motives ; coffee/caffeine ; systematic review and meta-analysis ; prospective studies ; epidemiology ; cancer prevention ; colorectal cancer ; individual responses ; responders ; exercise performance ; caffeine ; tea ; energy drinks ; pregnancy ; newborn ; ergogenic aid ; resistance training ; isokinetic testing ; adrenal gland ; corticosterone ; puberty ; rat ; sex-difference ; fatigue ; mood state ; supplement ; resistance exercise ; speed ; repetition ; n/a ; metabolome ; skeletal muscle ; muscle contraction ; ergogenic effect ; bench press ; upper limb ; ergogenic substances ; time under tension ; 1RM test ; metabolites ; phenotyping ; CYP450 ; NAT ; xanthine oxidase ; actigraphy ; athletic ; anaerobic ; CMJ ; nutrition ; sport supplement ; Wingate ; electromyography ; efficiency ; sport ; expectancy ; belief ; perceptions ; placebo effect ; recovery ; strength ; power ; sprint performance ; menstrual cycle ; placebo ; ergogenic ; EEG–EMG coherence ; women ; exercise training ; velocity ; muscle function ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PS Biology, life sciences ; bic Book Industry Communication::J Society & social sciences::JF Society & culture: general::JFC Cultural studies::JFCV Food & society
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  • 24
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2022-02-24
    Description: The book deals with therapeutic monoclonal antibodies (mAbs) broadly, and relevant topics such as challenges and opportunities, next-generation antibody products, Antibody-Drug-Conjugates (ADC), bispecifics, glycosylation, and T-cell engagers are covered. Each topic has been written by leading groups around the world and the book should be of interest to researchers from both academia and industry.
    Keywords: therapeutic antibody ; stability ; aggregation ; manufacture challenges ; formulation ; antibodies ; site-specific conjugation ; bioconjugates ; ADC ; antibody-drug conjugates ; payloads ; linkers ; nucleic acids ; ADME ; developability ; glycosylation ; post-translational modifications ; pharmacokinetics ; effector functions ; antibody-dependent cell-mediated cytotoxicity ; complement-dependent cytotoxicity ; immunogenicity ; pharmacodynamics ; glycoengineering ; type III secretion system ; prophylaxis ; antibacterials ; antibiotics ; HIV/AIDS ; co-formulation ; high concentration ; analytical characterization ; antibody (s) ; T-cell engagers ; bispecific antibodies ; immunotherapy ; oncology ; antibody engineering ; immunological synapse ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KND Manufacturing industries::KNDP Pharmaceutical industries
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  • 25
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2022-08-12
    Description: This colligated Special Issue of Pharmaceutics on Precision Medicine: Applied Concepts of Pharmacogenomics in Patients with Various Diseases and Polypharmacy offers to the reader a series of articles that describe the concept of Precision Medicine, discuss its implementation process and limitations, demonstrate its value by illustrating some clinical cases, and open the door to new and more sophisticated techniques and applications.
    Keywords: fibromyalgia (FM) ; myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) ; microRNA ; miRNome ; pharmacogenomics ; pharmacoepigenomics ; SM2miR ; Pharmaco-miR ; repoDB ; ME/CFS Common Data Elements (CDEs) ; dihydropyrimidine dehydrogenase ; DPYD ; 5-fluorouracil ; fluoropyrimidine ; therapeutic drug monitoring ; orthotopic liver transplant ; busulfan ; glutathione S-transferase ; genetic polymorphism ; limited sampling strategy ; pharmacokinetics ; clinical pharmacogenetics ; pharmacogenetic testing ; adverse drug reactions ; genotype ; phenotype ; pharmacogene ; barriers to pharmacogenetics implementation ; Sub-Saharan Africa ; chronic low back pain (cLBP) ; genetics ; personalized treatment ; polymorphism ; CYP450 ; tacrolimus ; CYP3A5 ; liver transplant ; pharmacogenomic ; minority ; data collection ; drug ; biomarker ; pharmacogenetics ; pharmacogenetic test ; personalized medicine ; gene expression ; infliximab ; adalimumab ; ulcerative colitis ; Crohn disease ; inflammatory bowel disease ; n/a ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::M Medicine::MJ Clinical & internal medicine
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  • 26
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-04-09
    Description: The use of lipid-based nanosystems, including lipid nanoparticles (solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC)), nanoemulsions, and liposomes, among others, is widespread. Several researchers have described the advantages of different applications of these nanosystems. For instance, they can increase the targeting and bioavailability of drugs, improving therapeutic effects. Their use in the cosmetic field is also promising, owing to their moisturizing properties and ability to protect labile cosmetic actives. Thus, it is surprising that only a few lipid-based nanosystems have reached the market. This can be explained by the strict regulatory requirements of medicines and the occurrence of unexpected in vivo failure, which highlights the need to conduct more preclinical studies.Current research is focused on testing the in vitro, ex vivo, and in vivo efficacy of lipid-based nanosystems to predict their clinical performance. However, there is a lack of method validation, which compromises the comparison between different studies.This book brings together the latest research and reviews that report on in vitro, ex vivo, and in vivo preclinical studies using lipid-based nanosystems. Readers can find up-to-date information on the most common experiments performed to predict the clinical behavior of lipid-based nanosystems. A series of 15 research articles and a review are presented, with authors from 15 different countries, which demonstrates the universality of the investigations that have been carried out in this area.
    Keywords: nanostructured lipid carriers (NLC) ; formulation optimization ; rivastigmine ; quality by design (QbD) ; nasal route ; nose-to-brain ; N-alkylisatin ; liposome ; urokinase plasminogen activator ; PAI-2 ; SerpinB2 ; breast cancer ; liposomes ; target delivery nanosystem ; FZD10 protein ; colon cancer therapy ; supersaturation ; silica-lipid hybrid ; spray drying ; lipolysis ; lipid-based formulation ; fenofibrate ; mesoporous silica ; oral drug delivery ; hyaluronic acid ; drug release ; light activation ; stability ; mobility ; biocorona ; dissolution enhancement ; phospholipids ; solid dosage forms ; porous microparticles ; nanoemulsion(s) ; phase-behavior ; DoE ; D-optimal design ; vegetable oils ; non-ionic surfactants ; efavirenz ; flaxseed oil ; nanostructured lipid carriers ; nanocarrier ; docohexaenoic acid ; neuroprotection ; neuroinflammation ; fluconazole ; Box‒Behnken design ; nanotransfersome ; ulcer index ; zone of inhibition ; rheological behavior ; ex vivo permeation ; nanomedicine ; cancer ; doxorubicin ; melanoma ; drug delivery ; ultrasound contrast agents ; phospholipid coating ; ligand distribution ; cholesterol ; acoustic response ; microbubble ; lipid phase ; dialysis ; ammonia ; intoxication ; cyanocobalamin ; vitamin B12 ; atopic dermatitis ; psoriasis ; transferosomes ; lipid vesicles ; skin topical delivery ; oligonucleotide ; self-emulsifying drug delivery systems ; hydrophobic ion pairing ; intestinal permeation enhancers ; Caco-2 monolayer ; clarithromycin ; solid lipid nanoparticles ; optimization ; permeation ; pharmacokinetics ; follicular targeting ; dexamethasone ; alopecia areata ; lipomers ; lipid polymer hybrid nanocapsules ; biodistribution ; skin ; ethyl cellulose ; n/a ; thema EDItEUR::T Technology, Engineering, Agriculture, Industrial processes::TB Technology: general issues
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  • 27
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2022-06-24
    Description: Drug–drug interactions (DDIs) cause a drug to affect other drugs, leading to reduced drug efficacy or increased toxicity of the affected drug. Some well-known interactions are known to be the cause of adverse drug reactions (ADRs) that are life threatening to the patient. Traditionally, DDI have been evaluated around the selective action of drugs on specific CYP enzymes. The interaction of drugs with CYP remains very important in drug interactions but, recently, other important mechanisms have also been studied as contributing to drug interaction including transport- or UDP-glucuronyltransferase as a Phase II reaction-mediated DDI. In addition, novel mechanisms of regulating DDIs can also be suggested. In the case of the substance targeted for interaction, not only the DDIs but also the herb–drug or food–drug interactions have been reported to be clinically relevant in terms of adverse side effects. Reporting examples of drug interactions on a marketed drug or studies on new mechanisms will be very helpful for preventing the side effects of the patient taking these drugs. This Special Issue aims to highlight current progress in understanding both the clinical and nonclinical interactions of commercial drugs and the elucidation of the mechanisms of drug interactions.
    Keywords: tadalafil ; ticagrelor ; drug-drug interaction ; pharmacokinetics ; plasma concentration ; CYP3A4 ; Loxoprofen ; CYP3A ; Dexamethasone ; Ketoconazole ; CYP2D6 ; O-desmethyltramadol ; physiologically-based pharmacokinetics ; tramadol ; (‒)-sophoranone ; CYP2C9 ; potent inhibition ; in vitro ; in vivo ; drug interaction ; low permeability ; high plasma protein binding ; biflavonoid ; cytochrome P450 ; drug interactions ; selamariscina A ; uridine 5′-diphosphoglucuronosyl transferase ; tissue-specific ; systemic exposure ; P-glycoprotein (P-gp) ; organic anion transporting polypeptide 1A2 (OATP1A2) ; Rumex acetosa ; fexofenadine ; chronic kidney disease ; drug–drug interactions ; polypharmacy ; adverse drug reactions ; Lexicomp ; subset analysis ; signal detection algorithms ; spontaneous reporting systems ; mechanism-based inhibition ; competitive inhibition ; non-competitive inhibition ; substrate ; inhibitor ; cytochromes P450 ; OATP1B1 ; OATP1B3 ; tyrosine kinase inhibitors ; drug-drug interactions ; migraine ; lasmiditan ; gepants ; monoclonal antibodies ; CYP1A1 ; CYP1A2 ; drug–drug interaction ; expression ; metabolism ; regulation ; drug transporter ; ubiquitination ; ixazomib ; DDI ; computational prediction ; in silico ; QSAR ; drug metabolism ; ADME ; CYP ; metabolic DDI ; P450 ; 1A2 ; 2B6 ; 2C19 ; 2C8 ; 2C9 ; 2D6 ; 3A4 ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PS Biology, life sciences
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  • 28
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2022-08-12
    Description: This book collects contributions published in the Special Issue “From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential” and dealing with successful stories of drug improvement or design using classic protocols, quantum mechanical mechanistic investigation, or hybrid approaches such as QM/MM or QM/ML (machine learning). In the last two decades, computer-aided modeling has strongly supported scientists’ intuition to design functional molecules. High-throughput screening protocols, mainly based on classical mechanics’ atomistic potentials, are largely employed in biology and medicinal chemistry studies with the aim of simulating drug-likeness and bioactivity in terms of efficient binding to the target receptors. The advantages of this approach are quick outcomes, the possibility of repurposing commercially available drugs, consolidated protocols, and the availability of large databases. On the other hand, these studies do not intrinsically provide reactivity information, which requires quantum mechanical methodologies that are only applicable to significantly smaller and simplified systems at present. These latter studies focus on the drug itself, considering the chemical properties related to its structural features and motifs. Overall, such simulations provide necessary insights for a better understanding of the chemistry principles that rule the diseases at the molecular level, as well as possible mechanisms for restoring the physiological equilibrium.
    Keywords: SARS-CoV-2 ; benzoic acid derivatives ; gallic acid ; molecular docking ; reactivity parameters ; selenoxide elimination ; one-pot ; imine-enamine ; reaction mechanism ; DFT calculations ; selenium ; anti-inflammatory drugs ; QSAR ; pain management ; cyclooxygenase ; multitarget drug ; cannabinoid ; neuropathic pain ; clopidogrel ; NMR study ; oxone ; peroxymonosulfate ; sodium halide ; thienopyridine ; drug discovery ; precision medicine ; pharmacodynamics ; pharmacokinetics ; coronavirus SARS-CoV-2 ; COVID-19 ; 3-chymotrypsin-like protease ; pyrimidonic pharmaceuticals ; molecular dynamics simulations ; binding free energy ; β-carrageenan ; antioxidant activity ; Box-Behken ; extraction ; Eucheuma gelatinae ; physic-chemistry ; rheology ; quercetin ; quercetin 3-O-glucuronide ; cisplatin ; nephrotoxicity ; cytoprotection ; lithium therapy ; neurocytology ; toxicology ; neuroprotection ; chemoinformatics ; big data ; methadone hydrochloride ; pharmaceutical solutions ; drug compounding ; high performance liquid chromatography ; stability study ; microbiology ; fucoidan ; alginate ; L-selectin ; E-selectin ; MCP-1 ; ICAM-1 ; THP-1 macrophage ; monocyte migration ; protein binding ; breast milk ; M/P ratio ; statistical modeling ; molecular descriptors ; chromatographic descriptors ; affinity chromatography ; anti-ACE ; anti-DPP-IV ; gastrointestinal digestion ; in silico ; molecular dynamics ; paramyosin ; seafood ; target fishing ; n/a ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::M Medicine::MM Other branches of medicine::MMG Pharmacology
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2022-07-06
    Description: Since first receiving approval in 1986, antibody-based therapeutics have been the most successful modality for the treatment of various diseases. This Special Issue of IJMS, “Recent Advances in Antibody Therapeutics”, presents leading-edge articles and reviews for discovery, development, and clinical applications of therapeutic antibodies, covering antibody drug conjugates (ADCs), GPCR-targeting antibodies, a functional antibody screening, bioassay of bispecific antibodies, antibody applications for cardiovascular diseases, antibody delivery to CNS, etc. The excellent studies in this Special Issue would valuable insight for scientists and clinicians in the field of therapeutic antibodies
    Keywords: interleukin 33 ; ST2 receptor ; scFv ; C2_2E12 ; bladder cancer ; antibodies ; immune checkpoint inhibitors ; antibody-drug conjugates ; sacituzumab govitecan ; enfortumab vedotin ; erdafitinib ; cost-effectiveness ; G protein-coupled receptor ; membrane protein ; antigen ; therapeutic antibody ; anti-angiogenesis ; delta-like ligand ; irinotecan ; paclitaxel ; VEGF ; SARS-CoV-2 ; spike protein ; receptor-binding domain ; phage display ; monoclonal antibody ; cytomegalovirus ; peptide/major histocompatibility complex class I complex ; T-cell-receptor-like antibody ; affinity maturation ; yeast surface display ; combinatorial antibody library ; agonist antibody ; cell fate ; bispecific antibodies ; bioassays ; mechanisms of action ; binding assays ; potency assays ; atherosclerosis ; inflammation ; antibody therapy ; blood–brain barrier ; antibody ; pharmacokinetics ; disposition ; biochemical and physicochemical properties ; Fc binding ; receptor-mediated transcytosis ; brain shuttle ; molecular Trojan horse ; transferrin ; anti-cancer antibody ; antibody engineering ; biophysical properties ; computational methods ; research cell bank ; antibody therapeutics ; recombinant antibodies ; intracellular antibodies ; single-chain antibody fragment ; nanobody ; Human papillomaviruses ; HPV oncoproteins ; HPV-associated cancer ; HPV cancer therapy ; asthma ; refractory asthma ; biomarker ; n/a ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PN Chemistry
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2022-10-25
    Description: Functional nutrition is deeply connected with healthy lifestyle and sustainable food production, due to its positive health benefits and the use of economically underexplored and natural raw materials. Expectedly, it appeals to large number of interested consumers while becoming lucrative segment of the food industry with a fast-growing market fueled by new sociodemographic trends. Accordingly, functional juices and beverages made of indigenous fruits are interesting niche for various food market stakeholders. Here, biologically active compounds (BACs) and probiotics that have positive health effects in functional foods (juices) are mostly thermolabile. This is especially important for industry that still employs classical heat treatments (e.g., pasteurization), while being concerned with degradation of food quality in the final products. To prevent this, focus is on designing economic and ecological technologies that are able to preserve nutritional and sensory quality while maintaining microbiological stability in products. Such approaches are based on low-energy consumption and low-impact processing, e.g. “hurdle technology” that combines advanced and conventional methods (e.g., high-power ultrasound, pulse electric field). Food design is another important focus point for consumers’ sensory appeal and economic success of foods. Hence, technologies as 3D food printing can be particularly useful for manufacturing. Based on the above, presented topics are relevant to sustainable functional food production, functional fruit juices, BACs, “hurdle technology,” advanced food processing, 3D food printing, and authentic fruits.
    Keywords: dehydration ; conserving vegetables ; improving shelf-life ; rehydrated pepper ; histological preparation ; green practices ; meat analogue ; liquid additives ; soy protein isolate ; lecithin ; emulsion ; functional fruit juice ; hurdle technology ; non-thermal processing ; preservation ; quality ; probiotic ; fruit by-products ; lulo bagasse powder ; fiber ; antioxidant properties ; carotenoids ; cocoa shell ; high voltage electrical discharge ; tannin ; dietary fiber ; water binding capacity ; grindability ; traditional ; slow ; pressure and microwave cooking ; polyphenols ; antioxidant activity ; faba bean ; lentil ; pea ; probiotic safety ; toxicity ; pathogenicity ; functional food industry ; pharmacological interactions ; functional fruit juices ; mushroom ; vitamin D ; reducing capacity ; glycation ; Lactuca sativa ; metabolomics ; antioxidants ; eustress ; total soluble solids ; particle size distribution ; total anthocyanin content ; antioxidant capacity ; non-dairy beverages ; pulses ; chickpea ; lupin ; flow behavior ; animal and plant proteins ; computer vision system ; nutritional value ; texture ; water activity ; viscosity ; microstructure ; heavy metals ; amino acids ; pesticide ; fruit wastes ; vegetable wastes ; drying ; extraction ; intensification technologies ; phenolic acids ; food processing ; minimally processed foods ; UHLPC-MS/MS ; sous-vide cooking ; vegetables ; seafood ; cephalopods ; safety ; nutritive quality ; beetroot ; convective drying ; infrared drying ; purée ; Fourier-transform infrared spectroscopy ; confocal scanning microscopy ; fruit juice ; interaction ; drug ; phytochemical ; pharmacokinetics ; ginger ; pineapple ; turmeric ; juice mix ; physicochemical properties ; microbiological quality ; sensory attributes ; Diospyros kaki ; post-harvest losses ; dehydrated persimmon ; thin-layer modeling ; drying rate ; old apple cultivar ; biologically active compounds ; functional food ; agriculture ; extensive farming ; bisphosphonates ; SERMs ; food ; supplements ; bioavailability ; meal ; coffee ; juice ; mineral water ; edible mushroom ; nutrition ; phenolic compounds ; vacuum ; poria cubes ; optimization ; stage drying ; n/a ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PS Biology, life sciences ; bic Book Industry Communication::T Technology, engineering, agriculture
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2022-10-25
    Description: In this Topical Collection, ten articles (one review and nine research articles) are published in a time span of 2021–2022. All articles are written by experts in the field of Separation Techniques who were invited to contribute to the presentation of the current status in separation science. The authors were invited to answer the questions: What is the state-of-the-art in Separation Sciences? What advances have been reported recently? Last but not least, what are the future perspectives? The Editor and authors hope that the readers will find valuable information in the topic.
    Keywords: protein-based chiral stationary phase ; alpha 1-acid glycoprotein ; chiral recognition mechanism ; molecular docking ; proteomics ; high-performance liquid chromatography ; mass spectrometry ; gout ; uric acid ; Salvia miltiorrhiza ; HPLC-MS/MS ; pharmacokinetics ; wine-processed ; hydrophilic interaction liquid chromatography ; chromatography ; oligopeptides ; acetyl hexapeptide-8 ; acetyl hexapeptide-3 ; Argireline ; cosmetics ; SARS-CoV-2 ; virus particles ; air filtering ; aerosols ; probability distributions ; rotational particle separator ; air separation ; steam methane reforming ; water gas shift ; alternative fluids ; gas turbine ; Senecio anteuphorbium ; response factors ; true quantitation ; allelopathy ; herbicide ; chlorpropham ; potato ; μQuEChERS/UHPLC-PDA ; validation ; cooking ; methyl nicotinate ; methyl salicylate ; ethyl salicylate ; 2-hydroxyethyl salicylate ; pain relief spray ; Tulasnellaceae sp. ; Gymnadenia orchidis ; mdium-pressure liquid chromatography ; reversed-phase liquid chromatography ; ergosterol ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PN Chemistry
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2022-06-21
    Description: There have been recent significant improvements in the short-term survival of solid organ transplantation patients due to advances in immunosuppression and transplant techniques. However, long-term graft survival has still lagged behind other outcomes and has now become one of the main problems in solid organ transplantation.For this Special Issue, we invited researchers and clinicians to submit studies on solid organ transplantation. These have provided us with additional knowledge and skills that will ultimately help us to improve outcomes after solid organ transplantation.
    Keywords: living donation ; nephrectomy ; hand-assisted laparoscopic nephrectomy ; body composition ; complications ; simultaneous pancreas-kidney transplantation ; immunosuppression ; graft order ; sequence ; outcome ; survival ; kidney transplantation ; hydrogen ; diarrhea ; small intestinal bacterial overgrowth ; sickle cell disease ; sickle cell ; transplantation ; outcomes ; big data ; tacrolimus ; metabolism ; C/D ratio ; cholesterol ; dyslipidemia ; LDL-C ; liver transplantation ; hematuria ; chronic kidney disease ; tocilizumab ; clazakizumab ; desensitization ; anti-HLA alloantibody ; post traumatic growth ; psychiatric morbidity ; network analysis ; ESAS ; MINI ; CPC ; DCPR ; distress ; demoralization ; alexithymia ; anxiety ; antibody-mediated rejection ; recurrent primary disease ; renal transplantation ; pancreas transplantation ; cold ischemia time ; delayed graft function ; Eurotransplant Senior Program ; end-stage renal disease ; intensive care unit ; bioimpedance analysis ; drug dosing ; lean body mass index ; pharmacokinetics ; tacrolimus C/D ratio ; mineral bone disorder ; parathyroidectomy ; parathyroid hormone ; osteoporosis ; bone fractures ; Contrast-enhanced ultrasound ; kidney perfusion ; kidney function ; kidney donation ; n/a ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::M Medicine::MM Other branches of medicine::MMG Pharmacology
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-12-21
    Description: Development of strategies to assist the movement of poorly permeable molecules across biological barriers has long been the goal of drug delivery science. In the last three decades, there has been an exponential increase in advanced drug delivery systems that aim to address this issue. However, most proprietary delivery technologies that have progressed to clinical development are based on permeation enhancers (PEs) that have a history of safe use in man. This Special Issue entitled “Transmucosal Absorption Enhancers in the Drug Delivery Field” aims to present the current state-of-the-art in the application of PEs to improve drug absorption. Emphasis is placed on identification of novel permeation enhancers, mechanisms of barrier alteration, physicochemical properties of PEs that contribute to optimal enhancement action, new delivery models to assess PEs, studies assessing safety of PEs, approaches to assist translation of PEs into effective oral, nasal, ocular and vaginal dosage forms and combining PEs with other delivery strategies.
    Keywords: R5-920 ; RM1-950 ; chitosan ; intestinal epithelial cells ; ocular delivery ; amphiphilic polymers ; cornea ; tight junction modulator ; cyclodextrin ; permeability ; gemini surfactant ; transferrin ; compound 48/80 ; epithelial permeability ; cervicovaginal tumors ; nanoparticles ; confocal laser scanning microscopy ; safety ; formulation ; salcaprozate sodium ; intestinal absorption ; FITC-dextran ; curcumin ; block copolymers ; nasal vaccination ; whole leaf ; brush border ; ocular drug delivery ; vaccine adjuvant ; nanoparticle ; nasal delivery ; efflux ; permeation enhancers ; absorption enhancers ; nose to brain delivery ; small intestine ; epithelium ; CNS disorders ; absorption modifying excipients ; insulin ; absorption enhancer ; gel ; intestinal delivery ; thermogel system ; Caco-2 ; biocompatibility studies ; absorption enhancement ; man ; PN159 ; poorly absorbed drug ; tryptophan ; tight junction ; oral macromolecule delivery ; penetration enhancer ; intestinal permeation enhancers ; nanocrystals ; simvastatin ; nanomedicine ; enterocyte ; N-dodecyl-?-D-maltoside (DDM) ; cell-penetrating peptide ; quaternization ; KLAL ; nasal ; nasal permeability ; transmucosal drug delivery ; Caco-2 cells ; mast cell activator ; penetration enhancers ; drug delivery ; nose-to-brain ; bioenhancer ; polymeric micelles ; mucoadhesion ; cell-penetrating peptide (CPP) ; simulated intestinal fluid ; vaginal delivery ; nasal formulation ; pharmacokinetic interaction ; sodium caprate ; clinical trial ; transmucosal permeation ; drug absorption enhancer ; sugar-based surfactants ; nanocapsules ; imatinib ; teriparatide ; osteoporosis ; hydrophobization ; F-actin ; combined microsphere ; transepithelial electrical resistance ; oral delivery ; ocular conditions ; metabolism ; antimicrobial peptide ; permeation enhancer ; drug administration ; antiepileptic drug ; amino acid ; in vivo studies ; sodium cholate (NaC) ; epithelial transport ; preclinical ; nose to brain transport ; pharmacokinetics ; chitosan derivatives ; ophthalmology ; tight junctions ; sheep ; cationic functionalization ; GLP-1 ; pulmonary ; and liposome ; cytochrome P450 ; claudin ; P-glycoprotein ; in situ hydrogel ; mucoadhesiveness ; PTH 1-34 ; Aloe vera ; oral peptides ; bic Book Industry Communication::M Medicine
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-04-05
    Description: The year 2019 has been prolific in terms of new evidence regarding the effects of coffee and caffeine consumption on diverse aspects of human functioning. This book collects 20 high-quality manuscripts published in Nutrients that include original investigation or systematic review studies of the effects of caffeine intake on human performance and health. The diversity of the articles published in this Special Issue highlights the extent of the effects of coffee and caffeine on human functioning, while underpinning the positive nature of most of these effects. This book will help with understanding why the natural sources of caffeine are so widely present in the nutrition behaviors of modern society.
    Keywords: QH301-705.5 ; Q1-390 ; TX341-641 ; NAT ; n/a ; supplementation ; EEG–EMG coherence ; muscle function ; tea ; fatigue ; ergogenic ; adrenal gland ; skeletal muscle ; xanthine oxidase ; placebo ; CMJ ; efficiency ; colorectal cancer ; rat ; pregnancy ; coffee/caffeine ; Wingate ; 1RM test ; supplement ; actigraphy ; athletic ; systematic review and meta-analysis ; women ; consumption motives ; resistance training ; cancer prevention ; sport supplement ; exercise ; DOMS ; placebo effect ; sprint performance ; power ; behavior ; belief ; health ; perceptions ; exercise performance ; ergogenic aid ; electromyography ; ergogenic effect ; corticosterone ; metabolome ; mood state ; muscle contraction ; strength ; energy drink ; repetition ; responders ; perception ; anaerobic ; CYP450 ; puberty ; energy drinks ; isokinetic testing ; individual responses ; phenotyping ; nutrition ; time under tension ; menstrual cycle ; exercise training ; RPE ; ergogenic substances ; upper limb ; elite athlete ; recovery ; speed ; epidemiology ; caffeine ; sex-difference ; bench press ; pharmacokinetics ; sport performance ; ergogenic aids ; expectancy ; consumer ; football ; newborn ; velocity ; metabolites ; performance ; coffee ; prospective studies ; resistance exercise ; sport ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-04-05
    Description: The amide bond represents a privileged motif in chemistry. The recent years have witnessed an explosion of interest in the development of new chemical transformations of amides. These developments cover an impressive range of catalytic N–C bond activation in electrophilic, Lewis acid, radical, and nucleophilic reaction pathways, among other transformations. Equally relevant are structural and theoretical studies that provide the basis for chemoselective manipulation of amidic resonance. This monograph on amide bonds offers a broad survey of recent advances in activation of amides and addresses various approaches in the field.
    Keywords: QD1-999 ; Q1-390 ; QD450-801 ; N-heterocyclic carbene ; non planar amide ; ruthenium (Ru) ; physical organic chemistry ; gemcitabine prodrug ; pyramidal amides ; bridged sultams ; catalysis ; dipeptides ; N-(1-naphthyl)acetamide ; C-N ? bond cleavage ; steric effects ; peptide bond cleavage ; transition-metal-free ; palladium ; N-heterocyclic carbenes (NHCs) ; addition reaction ; C–O activation ; rhodium ; metal complexes ; carbanions ; thioamidation ; amide bond ; intramolecular catalysis ; antiviral activity ; additivity principle ; pre-catalysts ; C–N bond cleavage ; bridged lactams ; C–H acidity ; arynes ; twisted amides ; organic synthesis ; amination ; Suzuki-Miyaura ; tert-butyl ; cyclopentadienyl complexes ; C-S formation ; enzymes ; DFT study ; sulfonamide bond ; N ; HERON reaction ; primaquine ; entropy ; amide activation ; amidation ; synthesis ; amide hydrolysis ; carbonylicity ; amide bond activation ; amide bond resonance ; aminosulfonylation ; molecular dynamics ; model compound ; in situ ; amide ; homogeneous catalysis ; heterocycles ; anomeric effect ; multi-component coupling reaction ; kinetic ; excited state ; C–H bond cleavage ; palladium catalysis ; amides ; thiourea ; formylation ; alkynes ; cis/trans isomerization ; amide C–N bond activation ; intein ; C-H functionalization ; succindiamide ; amide bonds ; crown ether ; aminoacylation ; directing groups ; cytostatic activity ; reaction thermodynamics ; acyl transfer ; transition metals ; N-dimethylformamide ; DMAc ; acylative cross-coupling ; C-H/C-N activation ; nickel catalysis ; antibacterial screening ; sodium ; aryl thioamides ; Winkler-Dunitz parameters ; catalyst ; N-dimethylacetamide ; base-catalyed hydrolysis ; nitrogen heterocycles ; cross-coupling ; insertion ; amidicity ; nitro-aci tautomerism ; activation ; carbonylation ; transamidation ; amine ; distortion ; Pd-catalysis ; rotational barrier energy ; hypersensitivity ; N–C activation ; metabolic stability ; [2+2+2] annulation ; twisted amide ; protease ; cyanation ; amide resonance ; trialkylborane ; catalysts ; biofilm eradication ; pharmacokinetics ; pancreatic cancer cells ; DMF ; aryl esters ; Michael acceptor ; fumardiamide ; water solvation ; ester bond activation ; cyclization ; nuclear magnetic resonance ; secondary amides ; reaction mechanism ; density functional theory ; density-functional theory ; amino acid transporters ; thema EDItEUR::P Mathematics and Science::PN Chemistry
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-12-21
    Description: Drug metabolism/pharmacokinetics and drug interaction studies have been extensively carried out in order to secure the druggability and safety of new chemical entities throughout the development of new drugs. Recently, drug metabolism and transport by phase II drug metabolizing enzymes and drug transporters, respectively, as well as phase I drug metabolizing enzymes, have been studied. A combination of biochemical advances in the function and regulation of drug metabolizing enzymes and automated analytical technologies are revolutionizing drug metabolism research. There are also potential drug–drug interactions with co-administered drugs due to inhibition and/or induction of drug metabolic enzymes and drug transporters. In addition, drug interaction studies have been actively performed to develop substrate cocktails that do not interfere with each other and a simultaneous analytical method of substrate drugs and their metabolites using a tandem mass spectrometer. This Special Issue has the aim of highlighting current progress in drug metabolism/pharmacokinetics, drug interactions, and bioanalysis.
    Keywords: R5-920 ; RM1-950 ; human liver microsomes ; alcohol addiction ; UGT ; ultra-high-pressure liquid chromatography ; adalimumab ; procainamide ; LC-MS/MS ; DA-9805 ; paeonol ; LC-QTOF-MS/MS ; YRA-1909 ; chlorogenic acid ; immunoprecipitation ; Eurycoma longifolia ; CYP ; caffeic acid ; rat ; pharmaceutical excipient ; Korean red ginseng extract ; Stauntonia hexaphylla leaf extract ; bioanalysis ; HPLC-MS/MS ; B6 ; eurycomanone ; bioavailability ; drying technology ; GB3 ; diclofenac ; 129-Glatm1Kul/J ; aglycone ; caffeic acid O-glucuronides ; organic anion transporting polypeptide ; protein precipitation ; metabolic stability ; Fabry disease ; biopharmaceuticals ; imperatorin ; neochlorogenic acid ; gastric ulcer ; saikosaponin a ; hair ; anthraquinone ; acetyl tributyl citrate ; pharmacokinetics ; brain distribution ; mematine ; ethyl glucuronide ; pharmacokinetic ; loxoprofen ; liquid chromatography-quadrupole TOF MS ; glucuronidation ; esomeprazole ; metformin ; cytochrome P450 ; glycoside ; AUDIT score ; protein stability ; efficacy ; LC-HR/MS ; cryptochlorogenic acid ; aceclofenac ; drug interaction ; liquid chromatography-tandem mass spectrometry ; Osthenol ; plasma ; N-acetylprocainamide ; diabetes ; bic Book Industry Communication::M Medicine
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-04-05
    Description: Spruce budworm (Choristoneura fumiferana (Clem.)) outbreaks are a dominant natural disturbance in the forests of Canada and northeastern USA. Widespread, severe defoliation by this native insect results in large-scale mortality and growth reductions of spruce (Picea sp.) and balsam fir (Abies balsamea (L.) Mill.) forests, and largely determines future age–class structure and productivity. The last major spruce budworm outbreak defoliated over 58 million hectares in the 1970s–1980s, and caused 32–43 million m3/year of timber volume losses from 1978 to 1987, in Canada. Management to deal with spruce budworm outbreaks has emphasized forest protection, spraying registered insecticides to prevent defoliation and keep trees alive. Other tactics can include salvage harvesting, altering harvest schedules to remove the most susceptible stands, or reducing future susceptibility by planting or thinning. Chemical insecticides are no longer used, and protection strategies use biological insecticides Bacillus thuringiensis (B.t.) or tebufenozide, a specific insect growth regulator. Over the last five years, a $30 million research project has tested another possible management tactic, termed an ‘early intervention strategy’, aimed at area-wide management of spruce budworm populations. This includes intensive monitoring to detect ‘hot spots’ of rising budworm populations before defoliation occurs, targeted insecticide treatment to prevent spread, and detailed research into target and non-target insect effects. The objective of this Special Issue is to compile the most recent research on protection strategies against spruce budworm. A series of papers will describe results and prospects for the use of an early intervention strategy in spruce budworm and other insect management.
    Keywords: QH301-705.5 ; Q1-390 ; SD1-669.5 ; pheromone mating disruption ; spruce budworm ; insecticide application ; multi-spectral remote sensing ; simulation ; apparent fecundity ; Choristoneura fumiferana (Clemens) ; Pinaceae ; Choristoneura fumiferana ; circadian rhythm ; forest protection ; early intervention strategy ; insect population management ; moth ; survival ; Phialocephala scopiformis ; moths ; optimized treatment design ; spatial-temporal patterns ; monitoring ; modelling ; science communication ; decision support system ; population control ; area-wide management ; tortricidae ; insect susceptibility ; egg recruitment ; annual defoliation ; treatment threshold ; Maine ; dispersal ; growth rate ; forest pests ; Choristoneura fumiferana (Clem.) ; mixed effect models ; intertree variance ; endophytic fungi ; Acadian region ; insecticides ; defoliation ; Abies balsamea ; Picea glauca ; immigration ; defoliation prediction ; early intervention ; Quebec ; phenology ; aerobiology ; economic losses ; spatial autocorrelation ; foliage protection ; computable general equilibrium model ; economic and ecological cost: benefit analyses ; hardwood content ; plant tolerance ; Lepidoptera ; migration ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-03-27
    Description: Sprouted grains are food ingredients widely appreciated for their improved nutritional, functional, organoleptic, and textural properties compared with non-germinated grains. In recent years, sprouting has been explored as a promising green food engineering strategy to improve the nutritional value of grains and the formation of secondary metabolites with potential application in the functional food, nutraceutical, pharmaceutical, and cosmetic markets. However, little attention has been paid to the impact of sprouting on the chemical composition, safety aspects, and technofunctional and chemopreventive properties of sprouted seeds and their derived flours and byproducts. The six articles included in this Special Issue present insightful findings on the most recent advances regarding new applications of sprouted seeds or products derived thereof, evaluations of the nutritional value and phytochemical composition of sprouts during production or storage, and explorations of their microbiological, bioactive, and technofunctional properties.
    Keywords: biochemical characteristic ; enzymatic browning ; inhibitory profile ; lentil ; sprouts ; polyphenol oxidase ; purification ; germinated oat ; avenanthramides ; colorectal cancer ; chemoprevention ; bran ; cell walls ; sprouting ; dough rheology ; bread-making ; microstructure ; barley ; germination ; flour ; RSM ; nutritional properties ; bioactive compounds ; quality ; melatonin ; bioavailability ; lentil sprouts ; phenolic compounds ; antioxidant status ; pharmacokinetics ; food safety ; legumes ; microbial contamination ; protein ; mineral ; seed germination ; nutritional value ; phytochemicals ; bioactivity ; health ; technological properties ; food development ; functional foods ; thema EDItEUR::G Reference, Information and Interdisciplinary subjects::GP Research and information: general
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-04-05
    Description: Throughout most of history, medicinal plants and their active metabolites have represented a valuable source of compounds used to prevent and to cure several diseases. Interest in natural compounds is still high as they represent a source of novel biologically/pharmacologically active compounds. Due to their high structural diversity and complexity, they are interesting structural scaffolds that can offer promising candidates for the study of new drugs, functional foods, and food additives.Plant extracts are a highly complex mixture of compounds and qualitative and quantitative analyses are necessary to ensure their quality. Furthermore, greener methods of extraction and analysis are needed today.This book is based on articles submitted for publication in the Special Issue entitled “Qualitative and Quantitative Analysis of Bioactive Natural Products” that collected original research and reviews on these topics.
    Keywords: QH301-705.5 ; Q1-390 ; Scorzonera ; capsaicinoids ; artificial neural network ; cerebral ischemia reperfusion injury ; antioxidant activity ; quality evaluation ; chemometrics ; secondary metabolites ; identification ; antioxidant capacity ; Moroccan region ; volatile compounds ; HPLC-Q-Exactive-Orbitrap-MS ; quantitative analysis ; amino acids content ; HPLC-ELSD ; antioxidant ; autophagy ; quantification ; sugars ; 1-triacontanol ; hemp seed oil ; Alzheimer’s disease ; macrodiolides ; extraction ; recycling preparative high performance liquid chromatography ; HPLC methods ; GC-MS ; Myristica fragrans ; Rossa da inverno sel. Rojo Duro onion cultivar ; fruit powders ; decursin ; food traceability ; ionic liquids ; separation optimisation ; Spondias spp. ; C-glycosylflavone ; wine ; UPLC-MS ; scutellarein ; saffron ; carotenoids ; red cabbage ; hydrodistillation ; Ginkgo biloba Extract (GBE) ; gas chromatography ; organic acids ; olive leaves ; crocins ; CBD oil ; Bolbostemma paniculatum ; UPLC-ESI-MS/MS ; geographical origin ; HPLC ; traditional Chinese medicine decoction ; liquid chromatography ; bioactive natural compounds ; Podospermum ; metabolic profiling ; SPME-GC/MS ; LTQ-Orbitrap ; oral administration ; UPLC ; bioactive compounds ; Erigeron breviscapus extract ; terrain conditions ; nutmeg ; antibacterial activity ; method validation ; ShenFu prescription decoction ; chili ; decursinol angelate ; statistical evaluations ; stereoselective and simultaneous analysis ; curcuminoids ; Talaromyces pinophilus ; talarodiolide ; HPLC-Q-TOF-MS/MS ; Olea europaea L. ; triterpenes ; chromatogram-bioactivity correlation ; essential oil ; stability ; Staphylococcus aureus ; Iris lactea Pall. var. chinensis (Fisch.) Koidz. ; endothelial function ; anthocyanins ; HPLC analysis ; liquid chromatography-mass spectrometry ; nodakenin ; turmerone ; UHPLC-MS/MS ; Quercus acuta leaf ; Curcuma longa ; UHPLC analysis ; ginseng berry extract ; geographical variation ; qualitative analysis ; Sorbus ; free radical-scavenging ; ginsenosides ; flavonoids ; biostimulant ; GC/MS ; terpenes ; aleuritolic acid ; phenolic compounds ; apoptosis ; response surface methodology ; phenolic acids ; pharmacokinetics ; mass spectrometry ; scutellarin ; multivariate statistical analysis ; phenolics ; MODDE experimental design ; proanthocyanidins ; UFLC-QQQ-MS ; rice ; cannabidiol ; odor-activity values ; UPLC-QTOF-MS ; turmeric ; decursinol ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences
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  • 40
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-04-05
    Description: This book entitled “Cocoa, Chocolate, and Human Health” presents the most recent findings about cocoa and health in 14 peer-reviewed chapters including nine original contributions and five reviews from cocoa experts around the world. Bioavailability and metabolism of the main cocoa polyphenols, i.e., the flavanols like epicatechin, are presented including metabolites like valerolactones that are formed by the gut microbiome. Many studies, including intervention studies or epidemiological observations, do not focus on single compounds, but on cocoa as a whole. This proves the effectiveness of cocoa as a functional food. A positive influence of cocoa on hearing problems, exercise performance, and metabolic syndrome is discussed with mixed results; the results about exercise performance are contradictive. Evidence shows that cocoa flavanols may modulate some risk factors related to metabolic syndrome such as hypertension and disorders in glucose and lipid metabolism. However, several cardiometabolic parameters in type 2 diabetics were not affected by a flavanol-rich cocoa powder as simultaneous treatment with pharmaceuticals might have negated the effect of cocoa. The putative health-promoting components of cocoa are altered during processing like fermentation, drying, and roasting of cocoa beans. Chocolate, the most popular cocoa product, shows remarkable losses in polyphenols and vitamin E during 18 months of storage.
    Keywords: QH301-705.5 ; Q1-390 ; TX341-641 ; n/a ; lipids ; theobromine ; colonic bacteria ; ?-glucosidase inhibition ; cacao ; tinnitus ; antioxidant capacity ; metabolomics ; methylxanthines ; lipid status ; physical exercise ; skeletal muscle ; functional volatile compounds ; soluble cocoa products ; blood pressure ; flavanols ; functional food ; classification ; monitoring ; cocoa ; yeast ; quality ; flavanols bioavailability ; fermentation ; cocoa processing ; hearing loss ; Italian chocolate ; chocolate ; (?)-catechin ; extraction and characterization methods ; heath potentials ; CREB ; inflammation ; flavanol-rich cocoa ; behavior ; (?)-epicatechin ; BDNF ; plasma appearance ; flavan-3-ol stereoisomers ; fermentation-related enzymes ; angiotensin-converting enzyme (ACE) inhibitory activity ; type 2 diabetes ; CaMKII ; exercise performance ; anti-inflammatory properties ; (+)-catechin ; bioactive compounds ; chiral separation ; plasma ; oxidative stress ; antidiabetic capacity ; polyphenols ; oligopeptides ; urine ; protein–phenol interactions ; postprandial ; working memory ; procyanidins ; simulated gastrointestinal digestion ; cocoa-based ingredients ; one-compartment model ; cocoa beans ; athlete ; biomarkers ; polyphenol ; metabolic syndrome ; nutrition ; bioavailability ; roasting ; glucose metabolism ; cohort study ; plasma nutrikinetics ; pharmacokinetics ; human ; cocoa proteins ; metabolites ; cocoa by-product ; meal ; bioactive peptides ; performance ; liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry (LC-ESI-QToF-MS) ; starter culture ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences
    Language: English
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  • 41
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2024-04-05
    Description: Carotenoids are a group of natural pigments, consisting of more than 750 compounds. They are mostly yellow, orange, or red in color, due to the system of conjugated double bonds. This structural element is also responsible for the good antioxidant properties of many carotenoids. Carotenoids have shown numerous biological activities (not only as provitamin A), e.g., preventive properties of fruits and vegetables. As lipophilic compounds, their uptake and storage in the body are dependent on various conditions. In vitro and in vivo data showed stimulating and inhibitory effects of matrix compounds on bioaccessibility and bioavailability of carotenoids.
    Keywords: QH301-705.5 ; Q1-390 ; singlet-triplet annihilation ; silicon carotenoids ; dye-sensitized solar cells ; spent coffee grounds ; astaxanthin ; antioxidant antagonism ; carotenoid and chlorophyll derivatives ; fluorocarotenoids ; RNS ; feed processing ; ?-carotene ; iodocarotenoids ; hydrophilic ; selenium carotenoids ; free radical kinetics ; mechanisms ; stability ; free radicals ; antioxidant ; soil amendment ; pressurized fluid extraction ; extraction ; metal ions ; lutein ; lettuce ; lycopene ; antioxidant synergism ; iron carotenoids ; ROS ; solubility ; flavonoids ; bromocarotenoids ; sulfur carotenoids ; marine carotenoids ; cationic lipid ; carotenoids ; antioxidants ; nelfinavir ; fruit ; SK-Hep-1 ; carotenoid ; storage ; vegetables ; ethanol ; exon skipping ; inflammation ; xanthophylls ; Duchenne muscular dystrophy ; pharmacokinetics ; carrots ; chlorocarotenoids ; chelating compound ; cardiovascular disease ; ageing ; accelerated solvent extraction ; nitrogen carotenoids ; VEGF ; chlorophyll ; liquid chromatography ; antiradical ; PEG conjugates ; injection solvent ; cycloaddition ; HIV ; esterification ; antisense oligonucleotide ; B16F10 ; interaction ; cancer chemoprevention ; antireductant ; PC-3 ; oxidative stress ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences
    Language: English
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  • 42
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-12-21
    Description: Viruses in the Parvoviridae family constitute one of the most diverse and intriguing fields of research. While they all share an ssDNA genome and a small capsid, they can differ widely in structure, genome organization and expression, virus–cell interaction, and impact on the host. Exploring such diversity and unraveling the inherent complexity in these apparently simple viruses is an ongoing endeavor and commitment for the scientific community. The translational implications of research on parvoviruses are relevant. Within the family, some viruses are important human and veterinary pathogens, in need of diagnostic methods and antiviral strategies; other viruses have long been studied and engineered as tools for oncolytic therapy, or as sophisticated gene delivery vectors, and can now display their wide and expanding applicative potential. This Special Issue of Viruses collects recent contributions in the field of parvovirus research, with a focus on new insights and research on unresolved issues, as well as new approaches exploiting systemic methodologies. Evolution, structural biology, viral replication, virus–host interaction, pathogenesis and immunity, and viral oncotherapy are a selection of the topics addressed in the issue that can be of relevance to the community involved in parvovirus research and of interest to a wider audience.
    Keywords: R5-920 ; RC109-216 ; antivirals ; Bombyx mori bidensovirus ; Bocaparvovirus ; human bocavirus 1 ; equine parvovirus-hepatitis ; NS2 ; NS1 ; X-ray crystallography ; BIRC3 (cIAP-2) ; glycans ; children ; antibody interactions ; new viruses ; alpaca ; cidofovir ; rodent protoparvoviruses ; clinical trials ; structural biology ; DNA virus ; human bocavirus ; caspase-3 ; viral communities ; uncoating ; PLA2 ; phospholipase-A2 ; oncolytic virus immune therapy ; Parvoviridae ; viral ecology ; Cryo-EM ; AAV ; metagenomics ; phylogeny ; oncolytic viruses ; mite ; parvovirus evolution ; Carnivore protoparvovirus 1 ; adeno-associated virus ; telbivudine ; capsid stability ; virus ; homology modeling ; human airway epithelia ; sequence analysis ; acute gastroenteritis ; bisulfite PCR ; next-generation sequencing ; single stranded DNA virus ; overlapping promoters ; virus diversity ; prognosis ; oncolytic activity ; genome ; hydroxyurea ; Lepidoptera ; genome externalization ; antiviral compounds ; circulating angiogenic cells ; tumor microenvironment ; coumarin derivatives ; nuclear targeting ; densovirus ; receptor interactions ; cell cycle arrest ; transcription profile ; brincidofovir ; canine parvovirus ; endogenous viral elements ; inflammatory cardiomyopathy ; erythroid progenitor cells ; RNA-seq ; insect ; chapparvovirus ; RT-qPCR ; trafficking ; AAV2 ; agricultural pests ; Adeno-associated virus ; myocarditis ; diagnosis ; parvovirus ; feline panleukopenia virus ; chitin ; B19V ; transcription mapping ; flavonoids ; immunomodulation ; erythrovirus ; apoptosis ; adenoviral vector ; anti-cancer ; divalent cations ; protease ; genetics ; preclinical ; arthropod ; peritrophins ; biocontrol ; dilated cardiomyopathy ; insect parvovirus ; combination therapies ; intravenous immunoglobulin (IVIG) ; virus phylogeny ; evolution ; second generation parvovirus treatments ; commercial horse serum ; parvovirus B19 ; canine chapparvovirus ; CpG methylation ; RACE ; H-1PV ; viral metagenomics ; horses ; bic Book Industry Communication::M Medicine
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  • 43
    Publication Date: 2023-12-20
    Description: After the successful conclusion of the Joint Meeting of IUFRO’s 7.03.05 & 7.03.10 working parties and given the exciting and novel studies that have been presented in the framework of this meeting, we decided to present some of these studies in the current Special Issue of Forests. To make this issue more appealing and interesting to everyone in the field of Forest Protection, studies that cover a wide range of topics were selected, ranging from ecology and phylogeography to forest management and protection. More importantly, as these studies refer to pests and pathogens from different parts of the world, it is expected that the knowledge gained can be further used in the protection of natural environment worldwide.
    Keywords: GE1-350 ; Q1-390 ; phenols ; flying ability ; Mediterranean forests ; wood borer insects ; Coraebus florentinus ; human-mediated transport ; ITS ; American chestnut ; sterols ; aggregated retention ; multivariate analysis ; Ips duplicatus ; Forestry Reclamation Approach ; triterpenes ; stand type ; Xyleborini ; birch ; Japanese red pine pure forests ; Scolytinae ; biological control ; Cephalcia kunyushanica ; deciduous forest ; silvicultural interventions ; fungal phytopathogens ; pathogen ; soil properties ; hypovirulence ; ammonium phosphite ; chestnut blight ; mtDNA ; latitude ; Cryphonectria parasitica ; occurrence ; distribution ; ash dieback ; ethanol ; phylogeography ; Carpathian Mountains ; Buprestidae ; stand characteristics ; oak ; vector ; Phytophthora ; black timber bark beetle ; infection level ; Romania ; coniferous forest ; Trypodendron laeve ; clearcutting ; Fraxinus excelsior ; selective pruning ; chlorophyll-a fluorescence ; forest management ; Ips sexdentatus ; disease management ; spread ; forest health ; ambrosia beetle ; Quercus ; invasive pathogens ; invasion ; biological invasion ; Lepidoptera ; ink disease ; functional group ; Betula ; mine reclamation ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCN Environmental economics
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  • 44
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    MDPI - Multidisciplinary Digital Publishing Institute
    Publication Date: 2023-12-21
    Description: Canada continues to have a rich history of ground-breaking research in drug delivery within academic institutions, pharmaceutical industry and the biotechnology community.
    Keywords: R5-920 ; RM1-950 ; encapsulation ; biodistribution ; pharmaceutics ; targeted therapies ; gambogic acid ; GE11 peptide ; formulation and dosage form development ; transient modulation ; ROESY NMR spectroscopy ; bioaccessibility ; polymeric micelle ; pharmacological Inhibitors of HIF-1 and STAT3 ; nanoparticles ; Vitamin D ; drug discovery ; EGFR-targeted therapy ; translational research ; clinical trials ; doxorubicin ; dissolution ; drug development ; permeation enhancers ; Canada ; plant ; primary central nervous system lymphomas ; photostabilizers ; head and neck squamous cell carcinoma ; mouse models ; drug delivery systems ; melphalan ; hypoxia-induced chemoresistance ; skin ; virus ; circadian clock ; child friendly formulation ; adenanthin ; co-delivery ; canola oil deodorizer distillate ; Metaplex ; innovation ; controlled drug delivery ; nifedipine ; radiolabeling ; amphotericin B ; biological barriers ; blood-brain barrier (BBB) ; biologicals ; lipid nanoparticles ; oral formulation ; phytosterols ; medical devices ; chronotherapy ; oral ; cationic gemini surfactant ; route of administration ; drug delivery ; intra-arterial chemotherapy ; developing world ; sustained delivery ; water miscible solvents ; combination therapy ; antibodies ; throughput ; magnetic fields ; liposomes ; medulloblastoma ; drug-resistant melanoma ; rosmarinic acid ; topical formulation ; TNO gastrointestinal model ; gastrointestinal simulator ; malignant gliomas ; transdermal drug delivery ; oral delivery ; precision medicine ; 3D spheroid ; flavonoids ; staurosporine ; DOX-Vit D ; loading gradients ; bacteriophage ; phospholipid complex ; triggered drug release ; HIF-1 ; phage display ; pharmacokinetics ; emulsion ; quercetin ; cisplatin ; parasitic infections ; remote loading ; HAV6 cadherin peptide ; blood-brain barrier ; inclusion complex ; tocopherols ; STAT3 ; ultrasound ; liposome ; fungal infections ; magnetic resonance imaging (MRI) ; MG63 ; model orange juice ; radiation ; cancer ; mefloquine ; small molecules ; bic Book Industry Communication::M Medicine
    Language: English
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  • 45
    Publication Date: 2017-04-04
    Description: We show the magnetic model of the Selli-Vavilov region. The Selli Line is known as the northwestern edge of the southern Tyrrhenian basin. The tectonic evolution of the Tyrrhenian basin is dominated by a Tortonian - Quaternary extension through the eastward movement of the Apennine subduction system. This migration has generated a diffuse stretching of the continental crust with the emplacement of new oceanic material. This latter occurred in several localized zones where the eastward retreating of the Ionian subduction system produced a strong depletion of the crust with formation of basins and correlated spreading. Nowadays the presence of oceanic crust is confirmed through direct drilling investigation but a complete mapping of the oceanic crustal distribution is still lacking. The Selli-Vavilov region shows a differentiated crustal setting where seamount structures, the oceanic basement portions and continental crust blocks are superimposed. To this aim, a 2D inversion of the magnetic data of this region was conducted to define buried structures. The magnetic susceptibility pattern was computed by solving the least squares problem of the misfit between the predicted and real data for separated wavebands. This method produced two 2D models of the high and low frequency fields of the Selli-Vavilov region. The two apparent susceptibility maps provide different information for distinct ranges of depth. The results of the inversions were also combined with seismic data of the Selli region highlighting the position of the highly-magnetized buried bodies. The results confirm a role for the Selli Line as a deep crustal boundary dividing the Sardinian passive domain from the easternmost active region where different oceanic structures are located. The Selli Line has worked as a detachment fault system which has moved eastward. Finally, the Selli-Vavilov region may be interpreted as a tectonic result due to a passive asymmetrical rift occurred between the Tortonian and Pliocene.
    Description: Published
    Description: 251-266
    Description: 2.6. TTC - Laboratorio di gravimetria, magnetismo ed elettromagnetismo in aree attive
    Description: 3.4. Geomagnetismo
    Description: 3.5. Geologia e storia dei sistemi vulcanici
    Description: JCR Journal
    Description: reserved
    Keywords: Geomagnetism ; Tectonics ; Geodynamics ; Inversion ; Oceanic crust ; Volcanic structure ; 04. Solid Earth::04.05. Geomagnetism::04.05.04. Magnetic anomalies ; 04. Solid Earth::04.07. Tectonophysics::04.07.02. Geodynamics ; 05. General::05.01. Computational geophysics::05.01.03. Inverse methods
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 46
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    3
    In:  Computers and Geosciences, Münster, 3, vol. 28, no. 45, pp. 309-326, pp. L11609, (ISBN 0-471-26610-8)
    Publication Date: 2002
    Keywords: Inversion ; Data analysis / ~ processing ; Non-linear effects ; Discrimination ; C&G
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  • 47
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    Springer
    In:  Berlin, 306 pp., Springer, vol. 2, no. XVI:, pp. 1-14, (ISBN: 0-387-30752-4)
    Publication Date: 2000
    Keywords: Textbook of geophysics ; Textbook of geology ; Textbook of mathematics ; Data analysis / ~ processing ; Modelling ; Inversion
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  • 48
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    Springer
    In:  New York, Springer, vol. 31, no. 3, pp. 2-203, (ISBN 0-87590-533-1)
    Publication Date: 2000
    Keywords: Data analysis / ~ processing ; Error analysis ; Handbook of geophysics ; Handbook of geodesy ; toolbox ; Statistical investigations ; Inversion ; Non-linear effects ; aerial ; images ; Diffraction ; Tomography ; 1214 ; Geodesy ; and ; gravity ; Geopotential ; theory ; and ; determination ; 1224 ; Photogrammetry ; remote ; sensing ; 0902 ; Exploration ; geophysics ; Computational ; methods, ; seismic ; Gruen ; Grun
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  • 49
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Tortricidae ; reproduction ; tebufenozide ; methoxyfenozide ; ecdysone agonist ; Argyrotaenia velutinana ; Choristoneura rosaceana
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The effects on the fecundity and fertility of redbanded leafroller, Argyrotaenia velutinana (Walker), and obliquebanded leafroller,Choristoneura rosaceana (Harris), exposed as adults to surfaces treated with the ecdysone agonists tebufenozide (RH-5992) and methoxyfenozide (RH-2485) were examined. The first part of the study consisted of recently emerged moths being exposed to treated surfaces continuously throughout their lives (including mating and oviposition). Continuous exposure to tebufenozide- or methoxyfenozide-treated surfaces significantly reduced the mean number of eggs laid and the percent of eggs that hatched in both species. The second part of the study involved exposure of recently emerged virgin moths (by sex) to treated surfaces for 24 h, after which, the exposed moths were paired with a nontreated partner to mate and oviposit on nontreated surfaces. In this experiment, for A. velutinana, significant reductions in fecundity occurred only when the female was exposed to methoxyfenozide-treated surfaces. Significant reductions in A. velutinana egg fertility occurred with both male and female exposure in the methoxyfenozide treatments and only female exposure in the tebufenozide treatments. For C. rosaceana, significant reductions in fecundity occurred with both male and female exposure in the tebufenozide and methoxyfenozide treatments. Significant reductions in C. rosaceana egg fertility occurred with both male and female exposure in the tebufenozide treatments and only with female exposure in the methoxyfenozide treatments.
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  • 50
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    Entomologia experimentalis et applicata 95 (2000), S. 217-227 
    ISSN: 1570-7458
    Keywords: antifeedant ; drimane ; mechanism of action ; sensory response ; toxicity ; habituation ; behavioural observation ; structure-activity relationship ; Pieris brassicae ; Lepidoptera ; Pieridae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We tested 11 analogous synthetic drimane antifeedant compounds for their feeding inhibiting effects on larvae of the large white butterfly Pieris brassicae L. (Lepidoptera: Pieridae) in no-choice tests on the host plant Brassica oleracea L. Furthermore, we observed larval feeding behaviour in no-choice tests to analyze temporal effects of five drimanes. The results show that the five analogous antifeedants differentially influence feeding behaviour and locomotion activity. Warburganal and polygodial are most likely sensory mediated antifeedants. Habituation to these compounds occurs soon after the onset of the tests (i.e., within 0.5–1.5 h). Compound 5 and confertifolin are probably not direct, sensory mediated antifeedants. After 0.5–1.5 h of exposure, these compounds inhibit not only feeding, but also locomotion behaviour, indicating postingestive, toxic effects. Isodrimenin inhibits feeding from the onset of the test and is probably a sensory mediated antifeedant. No habituation occurs to this compound, indicating that isodrimenin is either a very strong antifeedant or that it additionally has postingestive, toxic effects. Topical application of the drimanes on the larval cuticle revealed feeding inhibiting effects, but these could not be related to the occurrence of postingestive feeding inhibiting effects, indicating that this method is inappropriate to show possible postingestive effects of drimanes in P. brassicae. In conclusion, the behavioural observations performed in this research indicate that analogous drimanes inhibit feeding by P. brassicae larvae through multiple mechanisms of action. The results show that, when developing a structure activity relationship (SAR) for a series of antifeedants, it is important to distinguish the mode of action which underlies inhibition of feeding.
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  • 51
    ISSN: 1570-7458
    Keywords: Cnaphalocrocis medinalis ; rice leaffolder ; Lepidoptera ; Pyralidae ; sex pheromone ; geographical variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Sex pheromone components of the Japanese rice leaffolder moth, Cnaphalocrocis medinalis Guenée (Lepidoptera: Pyralidae) were identified from ovipositor extracts of virgin females as (Z)-11-octadecenal, (Z)-13-octadecenal, (Z)-11-octadecen-1-ol and (Z)-13-octadecen-1-ol at a ratio of 11:100:24:36 by GC-EAD, GC, GC-MS. The total amount was estimated to be ca.0.9 ng/female. Field bioassays in Kagoshima, Japan, showed that the two aldehydes are essential for male attraction and the alcohols may have a synergistic effect on the aldehydes. A rubber septum containing 0.9 mg of the four components at the natural ratio was shown to be an effective lure for monitoring this pest in Japan. The above four components are quite different from the sex pheromone components reported previously for the same species of either Philippine or Indian origin; components were shown to be (Z)-11-hexadecenyl acetate and (Z)-13-octadecenyl acetate at a ratio of 98:2 in the Philippine blend and 1:10 in the Indian blend. Furthermore, in the field tests in Japan, neither the Philippine blend nor the Indian blend showed any attractive activity, while the Japanese blend attracted significant numbers of male moths. These results suggest that there are remarkable geographical variations in the sex pheromone composition of this species or there are several distinct species using different sex pheromone blends.
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  • 52
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    Entomologia experimentalis et applicata 97 (2000), S. 137-147 
    ISSN: 1570-7458
    Keywords: Etiella zinckenella ; Etiella hobsoni ; Lepidoptera ; Pyralidae ; soybean ; development ; reproduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Experiments conducted in West Java, Indonesia investigated the developmental biology and reproductive behavior of two sympatric soybean pod borers, Etiella zinckenella Treitschke and E. hobsoni Butler (Lepidoptera: Pyralidae). It was determined that: (1) significant interspecific differences occurred between the egg, larval, pupal and total egg-to-adult developmental periods of laboratory raised E. zinckenella and E. hobsoni; (2) the pre-pupal and total egg-to-adult development periods of female E. zinckenella were significantly shorter than for males; (3) the longevity of virgin female E. zinckenella was significantly longer than that of virgin males, or virgin male and female E. hobsoni; (4) interspecific differences occurred in the female: male sex-ratios of laboratory raised adults; (5) peak mating for both species occurred on the second night after eclosion; (6) interspecific differences occurred in the temporal distribution of calling and mating behaviors; (7) repeated mating was observed for both species at a very low frequency; (8) interspecific mating did not occur; (9) female E. zinckenella were significantly more fecund than E. hobsoni; (10) the duration in copulo of E. zinckenella was significantly longer than that of E. hobsoni; and (11) wingtraps baited with virgin females caught only conspecific males, and reduced numbers of males were captured in traps simultaneously baited with virgin females of both species. This study demonstrates distinct biological differences and reproductive isolation between the two Etiella spp.
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  • 53
    ISSN: 1570-7458
    Keywords: calling behaviour ; periodicity ; sex pheromone ; attraction inhibitor ; attraction synergist ; field tests ; Lepidoptera ; Gracillariidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Females of the leaf miner moth Phyllonorycter acerifoliella (Z.) [=Ph. sylvella (Hw.)] and Ph. heegerella (Z.) (Lepidoptera: Gracillariidae: Lithocolletinae) release their sex pheromone at the beginning of photophase. The periodicity of the `calling' behaviour of Ph. acerifoliella females was established. Three compounds from calling virgin Ph. heegerella females were collected by the Solid Phase Micro Extraction (SPME) technique and identified as (Z)-8-tetradecenyl acetate (Z8-14:OAc), tetradecyl acetate (14:OAc) and (Z)-8-tetradecenol (Z8-14:OH) in the ratio (88±3):(2±0.6):(10±5) by capillary gas chromatography and mass spectrometry. Field trapping experiments demonstrated that the first two compounds are important for the attraction of conspecific males. Z8-14:OAc was found to be attractive when tested separately, while 14:OAc acted as synergist. The attractivity of the three component blend was reduced by 10% admixture of either (E)-10-dodecenyl acetate (E10-12:OAc) or (Z)-10-tetradecenyl acetate (Z10-14:OAc). Field tests of Z10-, Z8- and E10-14:OAc, identified from Ph. acerifoliella females, demonstrated that the first two compounds were essential for the attraction of conspecific males; so both are sex pheromone components. The attractivity of the three component blend of Z10- Z8- and E10-14:OAc was reduced by 10% admixture of (E)-10-dodecenol (E10-12:OH). The following four semiochemical compounds, Z8-14:OAc, Z8-14:OH, E10-14:OAc and 14:OAc, identified from phyllonoryctid females, as well as two sex attraction antagonists for Ph. acerifoliella and Ph. heegerella males, E10-12:OAc and Z10-14:OAc, are new for the family Gracillariidae. The results of field trapping experiments revealed mechanisms ensuring the specificity of the chemocommunication systems in Ph. acerifoliella, Ph. heegerella and Ph. ulmifoliella (Hb.) moths.
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  • 54
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    Entomologia experimentalis et applicata 97 (2000), S. 339-346 
    ISSN: 1570-7458
    Keywords: crygenes ; PCR ; Lepidoptera ; Spodoptera ; insecticidal activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Thirty-five strains of the entomopathogenic bacterium Bacillus thuringiensisactive on Spodoptera exigua, were characterized by means of serological identification and determination of crygene contents by PCR. The insecticidal activity of these 35 strains was further confirmed against S. exiguaand tested against two other species of the same genus: S. littoralisand S. frugiperda. The results indicate that serovars aizawai, thuringiensis, and kurstakiwere the most frequent within S. exigua-active strains and that serovar aizawaihad the highest number of strains exhibiting toxicity against the three species bioassayed. The presence in crygenes as determined by PCR suggests a non random distribution of some crygenes among serovars. Genes cry1C, cry1D, and cry1E, which are known to code for proteins toxic against Spodopteraspecies, were very common within S. exigua-active strains, specially in those belonging to serovar aizawai. However, some strains harbouring one or more of these genes were not toxic to S. littoralisor S. frugiperda; and some strains lacking all of the Spodoptera-active genes were found to be toxic to all three species. This suggests differences in the expression levels among strains bearing toxic genes and the involvement of other genes toxic to Spodopteraspecies. Since strains sharing the same crygenes exhibited different host ranges, the results indicate the need to perform toxicity bioassays in addition to other tests (serological identification and PCR) in order to determine the insecticidal activity of B. thuringiensisstrains.
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  • 55
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    Journal of insect behavior 13 (2000), S. 881-900 
    ISSN: 1572-8889
    Keywords: three-dimensional ; flight track recording ; orientation ; pheromones ; plant volatiles ; image analysis ; real time ; Lobesia botrana ; Lepidoptera ; Tortricidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A computer-controlled video system for real-time recording of insect flight in three dimensions is described. The flight paths of moths were recorded in a flight tunnel using two CCD cameras placed adjacent to each other at angles of 45 and 135° to the flight tunnel axis and separated by a distance of 120 cm. They were connected to two 28-level gray-scale frame grabbers via two external synchronizers. The two-dimensional coordinates of the flying insect were obtained from the two cameras at 40-ms intervals and transferred to host computer for processing and monitor for real-time display. Due to speed limitation in the image acquisition hardware, construction of the three-dimensional file was carried off-line. The flying insect was rendered as a dark spot in a bright background using a homogeneous light source. As the insect enters into the field of view of the two cameras, the light distribution changes, and the frame grabber detects only those variation in the light distribution which results from a flying insect. The target insect can be as small as 3 pixels and can be tracked in a stereoscopic field of view 60 cm long and 50 cm high. A method was developed that allowed for scalar scoring of various pheromone sources to assess their attractiveness using vector flight parameters. This method was applied successfully for optimization of pheromone blend of the grapevine moth, Lobesia botrana.
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  • 56
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    Geometriae dedicata 83 (2000), S. 31-37 
    ISSN: 1572-9168
    Keywords: Vollständiges Viereck ; Kegelschnittbüschel ; Konjugiertheitsabbildung ; Inversion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract The conjugacy mapping rel. to a complete quadrangle in a Pappian projective plane of characteristic ≠2 is constructed by using a bijection of the line set onto the bundle of conics through the diagonal points of the quadrangle. The inversion with center O of the inversion circle going through the point P in the Euclidean plane proves to be the product of the reflection at OP and the affine restriction of the conjugacy mapping rel. to the quadrangle having P as one of its vertices and O together with the circular points at infinity as diagonal points.
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  • 57
    ISSN: 1437-5613
    Keywords: Key words Herbivory ; Plant–herbivore interaction ; Lepidoptera ; Cruciferous plants ; Vegetation texture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Correlation between plant size and reproductive output may be modified by herbivory in accordance with host plant density and the presence of nonhost plants. To elucidate the effects of nonhost plant density and host plant density on the intensity of herbivory and reproductive output of the host plant in relation to plant size under natural conditions, we investigated the abundance of three lepidopteran insects, Plutella maculipennis, Anthocharis scolymus, and Pieris rapae the intensity of herbivory, and fruit set of their host plant, Turritis glabra (Cruciferae). To elucidate the effects of nonhost and host plant density, we selected four categories of plots under natural conditions: low density of nonhost and high density of host plants; low density of both nonhost and host plants; high density of both nonhost and host plants; and high density of nonhost and low density of host plants. The plant size indicated by stem diameter was a good predictor of the abundance of all herbivorous species. The effects of density of nonhost and host plants on the abundance of insects varied among species and stages of insects. As the abundance of insects affected the intensity of herbivory, herbivory was more apparent on larger host plants in plots with low density of both nonhost and host plants. Consequently, the correlation between plant size and the number of fruits disappeared in low plots with density of both nonhost and host plants. In this T. glabra– herbivorous insect system, the density of nonhost plants and host plants plays an important role in modifying the relationship between plants and herbivores under natural conditions.
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  • 58
    ISSN: 1437-5613
    Keywords: Key words Community patterns ; Lepidoptera ; Route order ; Species richness ; Species distribution ; Environmental disturbance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Kitahara and Fujii, in 1994, analyzed the butterfly communities along a gradient of human disturbance by applying the generalist/specialist concept. Butterfly species were classified into generalist or specialist species based on their voltinism (seasonal time dimension) and potential larval resource breadth (food dimension). The community structure and species composition showed the systematic changes along the gradient. To verify the generality of those trends, we monitored five grassland butterfly communities with varying degrees of human disturbance twice a month during 1985 by the line transect method at the foot of Mt. Fuji, central Japan, and analyzed their structure in a manner similar to that employed by Kitahara and Fujii. Most results were consistent with the patterns recognized by Kitahara and Fujii. The route (community) order based on increasing human disturbance was strongly and negatively correlated with butterfly species richness but with neither butterfly species diversity (H′) nor evenness (J′). Also, the degree of human disturbance was significantly and negatively correlated with the number of specialist species, but not with that of generalists, in a community. Butterfly species richness was more strongly correlated with the number of specialist species than with that of generalists. Our analyses also showed that the generalist species were distributed more widely over the communities than were the specialists. However, in contrast to the trend revealed by Kitahara and Fujii, there was no significant difference in the population densities and in the spatial population variability between the two species groups. As a whole, our analyses confirmed the consistency of most community patterns detected by Kitahara and Fujii. The causes of the inconsistencies in some patterns were thought to be mainly the present habitat conditions with a relatively short growing season at high altitudes.
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  • 59
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    Journal of insect conservation 4 (2000), S. 73-77 
    ISSN: 1572-9753
    Keywords: mapping ; database ; bias recording ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Nature of Science, Research, Systems of Higher Education, Museum Science
    Notes: Abstract We use data from the Mersey Valley zone (3×2 km area; N = 600 I ha squares) of the Greater Manchester butterfly atlas to investigate whether recorder visits are biased by access (viz. distance from recorder's home base) and by the locations of potential hot spots. In a multiple regression analysis, visits were found to correlate significantly both with distance from home base of the recorder and with the mean and maximum number of species found in squares. Sites close to the home base of the recorder were visited more frequently than those further afield and squares with more species were visited more frequently than those squares with fewer species. Visits were also made significantly more frequently to squares with greater numbers of butterfly resources (e.g. hostplants, nectar). Furthermore, recording is biased to and away from distinct land uses, which vary significantly in species richness. Reasons are given why these biases are to be expected at all scales. The message is that future distribution mapping should be based on rigorous sampling approaches.
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  • 60
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    Environmental geology 39 (2000), S. 360-371 
    ISSN: 1432-0495
    Keywords: Key words Environmental geophysics ; Resistivity ; Inversion ; Landfill mining ; Waste ; Characterization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Notes: Abstract  Geophysical investigations using 2-D DC resistivity were carried out on old parts of two similar landfills, with waste of different ages. The data sets, which included high data density in both vertical and horizontal directions, were interpreted with 2-D smoothness constrained inversion. The landfills were excavated after the surveying. The objective was to test the capability of the resistivity method as a pre-characterization technique. The objectives were only partially fulfilled. First, the moisture content was the parameter that appeared to exert the dominant control over the resistivity distribution of the landfill. The most important potential information that can be recovered is, therefore, an indication of the waste piles hydraulics. Second, it was neither possible to estimate the amount of recoverable soils, nor to correlate the type of waste with the resistivity models. However, discrete anomalies were identified, and if specific materials are searched for, the resistivity models indicate possible places to search.
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  • 61
    ISSN: 1432-1211
    Keywords: Key words Vβ13 ; CD4/CD8 ratio ; Rat ; Tcrb ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Three rat BV13S1 alleles (T-cell receptor β-chain variable gene 13) were characterized by new BV13S1-allele specific monoclonal antibodies (18B1 and 17D5) and sequence analysis of expressed and genomic BV13S1. Two alleles were functional and designated BV13S1A1 present in strains LEW, BUF, PVG, and BV13S1A2 present in BN and WF. Their products differed by six amino acids, two of them in complementarity-determing region (CDR)1 and one in CDR2. A third nonfunctional allele, BV13S1A3P, was found in strains F344 and DA. Apart from a single nucleotide insertion, it was identical to BV13S1A2. All 12 rat strains tested showed association of TCRBC1 with BV8S2/4 alleles but not with the BV13S1 alleles, which may reflect a different gene order of the rat BV compared to mouse. BV13S1A1-encoded T-cell receptors (TCRs) which bind both monoclonal antibody (mAb) 18B1 and mAb 17D5 are over-represented in the CD4 lymphocyte subset. BV13S1A2-encoded TCRs which are stained by mAb 18B1 but not by mAb 17D5 show a slight CD8-biased expression. Preferential usage of BV13S1A1-positive TCRs by CD4 but not by CD8 cells in (LEW×WF)F1 hybrids and cosegregation of BV13SA1 and increased frequency of BV13S1 TCR-positive CD4 cells in a (LEW×BN)×BN backcross suggest structural differences of the two allelic products as the reason for their contrasting CD4/CD8 subset bias.
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  • 62
    ISSN: 1432-119X
    Keywords: Endothelin-A receptor ; Endothelin-B receptor ; Rat ; Pulmonary fibrosis ; Immunohistochemistry ; Quantitative PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: AbstractPulmonary fibrosis is characterized by excessive extracellular matrix deposition with concomitant loss of gas exchange units, and endothelin-1 (ET-1) has been implicated in its pathogenesis. Increased levels of ET-1 from tissues and bronchoalveolar lavage have been reported in patients with pulmonary fibrosis and in animal models after intratracheal bleomycin. We characterized the cellular distribution of alveolar ET receptors by immunohistochemistry in bleomycin-induced pulmonary fibrosis in the rat and determined the regulation by bleomycin of ET receptor mRNA expression in isolated alveolar macrophages and rat lung fibroblasts. We found significant increases in the numbers of fibroblasts and macrophages at day 7 compared to day 28 and control animals. ETB receptor immunoreactivity was observed on fibroblasts and invading monocytes. Isolated fibroblasts expressed both ETA and ETB receptor mRNA, and ETA receptor mRNA was upregulated by bleomycin. Isolated resident alveolar macrophages expressed neither ETA nor ETB receptor mRNA which were also not induced by bleomycin. We conclude that, while ETB receptor stimulation of fibroblasts and monocytes recruited during bleomycin-induced lung injury exerts antagonistic effects on fibroblast collagen synthesis, the observed increase in the number of fibroblasts in vivo and upregulation of fibroblast ETA receptor mRNA by bleomycin in vitro point to a predominance of the profibrotic effects of ET receptor engagement.
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  • 63
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    Oecologia 122 (2000), S. 1-10 
    ISSN: 1432-1939
    Keywords: Key words Distribution ; Gregariousness ; Larval strategy ; Lepidoptera ; Thermoregulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Group-living in animal populations has many possible ecological and evolutionary explanations, including predator evasion and feeding facilitation. In insects, the thermal balance of solitary and gregarious larvae is likely to differ and may thus have important ecological consequences. The abilities of the larvae of four species of nettle-feeding nymphalid butterflies to thermoregulate were quantified in the field. Larval surface body temperatures of the gregarious Aglais urticae (small tortoiseshell) and Inachis io (peacock) and the solitary Polygonia c-album (comma) and Vanessa atalanta (red admiral) were measured for each instar, in both sunny and overcast conditions, over a seasonal range of temperatures. The results suggested two distinct larval thermal strategies. In the presence of direct sunlight, the exposed gregarious larvae of A. urticae and I. io regulated body temperatures at 32.5 and 31.5°C, respectively, while the temperatures of concealed larvae of P. c-album and V. atalanta were largely dependent on ambient temperatures. In the sun, the range of body temperatures recorded for A. urticae and I. io larvae was fairly narrow relative to ambient temperatures. This suggests a high degree of thermal control in these species. Modal body temperatures coincided with the temperature at which development rate is maximal. Regardless of whether changes in thermoregulation are a cause or consequence of the evolution of gregariousness, the combination of behavioural thermoregulation and gregariousness in larval insects has important implications for voltinism patterns and range extension (via increased development rates). Distributional responses of gregarious and solitary larvae to climatic warming may differ as a result of changes in cloud cover as well as changes in temperature.
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  • 64
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    Oecologia 122 (2000), S. 36-43 
    ISSN: 1432-1939
    Keywords: Key words Life history theory ; Longevity ; Ageing ; Mortality rate ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Life history theory predicts that organisms should only invest resources into intrinsic components of life span to the degree that it pays off in terms of reproductive success. Here, we investigate if the temporal distribution of mating opportunities may have influenced the evolution of intrinsic mortality rates in the butterfly Pararge aegeria (Satyrinae). In this species, females mate only once and the frequency of male mating opportunities depends on the temporal emergence pattern of virgin females. As expected, in a population from Madeira where females emerge continuously throughout the year, there was no sex difference in adult life span, while in a Swedish population with synchronised female emergence, males had significantly shorter life spans compared to females. A logistic mortality model provided the best fit to the observed change in age-specific mortality and all categories reached an asymptotic mortality rate of a similar magnitude. However, the Swedish males reached this mortality plateau more rapidly than the other categories. External mortality, due to water and food limitation, affected the pattern of sex-specific mortality but males from Sweden still had higher rates of mortality compared to all other categories. We argue that selection on male longevity is likely to be weaker in Sweden because under synchronised emergence, all females emerge and mate within a short period of time, after which male reproductive value will quickly approach zero. On Madeira, however, male reproductive value decrease more slowly with age since the probability of finding a receptive female is constant over the year.
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  • 65
    ISSN: 1573-1561
    Keywords: Insect pheromones ; pheromone emission ; aggressive chemical mimicry ; predation ; allomone ; Araneae ; Araneidae ; Lepidoptera ; Noctuidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The adult female bolas spider Mastophora hutchinsoni feeds exclusively on attracted males of a few moth species. This exclusivity and the behavior of the approaching moths suggest that the spider aggressively mimics the sex pheromones of its prey species. Males of the bristly cutworm, Lacinipolia renigera, are a major prey of this spider, accounting for about two thirds of the biomass of prey consumed. Female bristly cutworms produce a pheromone blend consisting of (Z)-9-tetradecenyl acetate (Z9–14 : Ac) and (Z,E)-9,12-tetradecenyl acetate (ZE-9,12–14 : Ac). To determine if M. hutchinsoni females mimic the sex pheromone components and blend ratio of L. renigera, we collected volatiles from hunting adult female spiders and analyzed them with gas chromatography–electroantennographic detection (GC-EAD) and gas chromatography–mass spectrometry (GC-MS). GC-EAD analysis of volatile collections, using a male bristly cutworm antenna as the detector and two capillary columns of different polarities, revealed the presence of peaks with retention times (R ts) identical to Z9–14 : Ac and ZE-9,12– 14 : Ac. The mass spectrum of a peak with R t of Z9–14 : Ac was identical to the mass spectrum of the synthetic equivalent. There was an insufficient quantity of the compound with R t of ZE-9,12–14 : Ac to get a full spectrum, but selective detection of ions at m/z 61 and 192 at the correct R t supported the identification. On average, the blend collected from spiders contained 54.8 ± 20.8 (SE) pg/min of Z9–14 : Ac and 2.5 ± 1.7 (SE) pg/min of ZE-9,12–14 : Ac. The latter, on average, comprised 2.6 ± 0.7% of the total, which is similar to the blend ratio emitted by bristly cutworm females. Our results indicate that the adult female M. hutchinsoni produces an allomone blend that mimics not only the composition, but also the blend ratio, of the sex pheromone of a major prey species.
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  • 66
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    Journal of chemical ecology 26 (2000), S. 1983-1990 
    ISSN: 1573-1561
    Keywords: Setora nitens ; Setothosea asigna ; nettle caterpillar ; Limacodidae ; Lepidoptera ; sex pheromone ; (Z)-9-dodecenal ; (Z)-9,11-dodecadienal ; (E)-9-dodecenal ; (E)-9,11-dodecadienal ; oil palm ; Elaeis guineensis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Gas chromatographic–electroantennographic detection (GC-EAD) analyses of pheromone gland extracts of female nettle caterpillars, Setora nitens, revealed four compounds that consistently elicited responses from male moth antennae. Retention indices on three fused silia columns (DB-5, DB-23, and DB-210) of two EAD-active compounds were almost identical to those of (E)-9-dodecenal (E9–12 : Ald) and (E)-9,11-dodecadienal (E9,11–12 : Ald), two pheromone components previously identified in congeneric Setothosea asigna. However, comparative GC, GC-EAD, and GC-mass spectrometry of extracted S. nitens compounds and authentic standards revealed that the candidate pheromone components were (Z)-9-dodecenal (Z9–12 : Ald) and (Z)-9,11-dodecadienal (Z9,11–12 : Ald). The two other EAD-active compounds in pheromone gland extracts proved to be the corresponding alcohols to these aldehydes. In field-trapping experiments in Tawau, Malaysia, synthetic Z9–12 : Ald and Z9,11–12 : Ald at a 1 : 1 ratio, but not singly, attracted male S. nitens. Attractiveness of these two aldehydes could not be enhanced through the addition of their corresponding alcohols. Whether these differences in pheromone biology and chemistry between S. nitens and S. asigna are sufficient to prevent cross-attraction of heterospecific males or whether nonpheromonal mechanisms are required to maintain reproductive isolation is currently being studied.
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  • 67
    ISSN: 1432-0762
    Keywords: Key words Copulation duration ; Explosive mating system ; Ejaculate size ; Lepidoptera ; Mating history
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The mating system of the Australian lycaenid butterfly, Jalmenus evagoras, is highly unusual compared to most other Lepidoptera. Characteristics of this system, which has been termed an ’explosive mating strategy,’ include the formation of an intensely competitive mating aggregation of males, a highly male biased operational sex ratio, a lack of discrimination and mate choice by both sexes, a high variance in male mating success, and female monogamy. In this study, we tested the hypothesis that multiple mating by males imposes physiological costs resulting in smaller spermatophores, and that this results in a fitness cost to females. We found that male J. evagoras transferred only 2.2% of their eclosion weight during their first mating, consistent with the hypothesis that males of monandrous species produce a relatively small investment. The wet weight of the ejaculate declined by an average of 27% at the second mating and the dry weight by 29%, and an intermating interval of 5–9 days was needed for the ejaculate to return to the size at the first mating, regardless of male size or age. Wet ejaculate mass increased proportionally with male size, though dry mass was proportionally larger in smaller males. Ejaculate mass tended to increase with male age at both first and second matings. Female characteristics, in general, did not affect ejaculate mass, although the wet weight of the ejaculate was positively associated with female weight at the second mating. Copulation duration increased from 2.4 h to approximately 3 h at the second mating, and to over 4 h at the third and fourth matings. Fecundity was positively correlated with female size but not with mating history, copulation duration, or any other characteristics measured for either males or females. Female longevity declined significantly as the number of times the male partner had previously mated increased. We conclude that despite the small male investment in ejaculate, the costs of multiple mating may nonetheless be significant, as indicated by the reduction in ejaculate mass, an increase in copulation duration, and reduction in female lifespan with increasing mating number.
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  • 68
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    Investigational new drugs 18 (2000), S. 373-381 
    ISSN: 1573-0646
    Keywords: clinical pharmacology ; dihydropyrimdine dehydrogenase ; eniluracil ; oral 5-FU ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacological inactivation of dihydropyrimidine dehydrogenase (DPD)represents one strategy to improve 5-FU therapy, which historically hasbeen associated with unpredictable pharmacological behavior andtoxicity. This is principally due to high interpatientdifferences in the activity of DPD, the enzyme that mediates theinitial and rate-limiting step in 5-FU catabolism. Byinactivating DPD and suppressing the catabolism of 5-FU,eniluracil has dramatically altered the pharmacological profileof 5-FU. The maximum tolerated dose of oral 5-FU given with oraleniluracil (1.0 to 25 mg/m2) is substantially lower thanconventional 5-FU doses. In the presence of eniluracil,bioavailability of 5-FU has increased to approximately 100%, thehalf-life is prolonged to 4 to 6 hours, and systemic clearanceis reduced 〉 20-fold to values comparable the glomerularfiltration rate (46 to 58 mL/min/m2). Renal excretion(∼ 45% to 75%), instead of DPD-related catabolism, is theprincipal route of elimination of oral 5-FU given witheniluracil. Chronic daily administration of oral 5-FU 1.0mg/m2 twice daily with eniluracil 20 mg twice dailyproduces 5-FU steady-state concentrations (8–38 ng/mL) similarto those achieved with protracted intravenous administration onclinically relevant dose-schedules. On a daily × 5regimen, higher 5-FU AUC values are related to neutropenia,whereas elevated 5-FU AUC and steady-state concentrations arerelated to diarrhea when oral 5-FU is given daily with eniluracilon a chronic schedule. The pharmacokinetic behavior of oraleniluracil is similar to that for oral 5-FU. Administration ofeniluracil 10 to 20 mg twice daily completely inactivates DPDactivity both in peripheral blood mononuclear cells and incolorectal tumor tissue, and prolonged inhibition of DPD afterdiscontinuation of eniluracil treatment has been noted. In thepresence of eniluracil, oral administration of 5-FU is feasibleand variation in 5-FU exposure is reduced, with the anticipationof further reduction in variation as dosing guidelines based onrenal function are formulated.
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  • 69
    ISSN: 1573-904X
    Keywords: allometric scaling ; interspecies scaling ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate (1) allometric scaling of systemic clearance (CL)using unbound drug concentration, (2) the potential usage of brainweight (BRW) correction in allometric scaling of both CL and oralclearance (CL/F). Methods. Human clearance was predicted allometrically (CLu = a ·Wbiv) using unbound plasma concentration for eight Parke-Daviscompounds and 29 drugs from literature sources. When the exponent bivwas higher than 0.85, BRW was incorporated into the allometricrelationship (CLu*BRW = a · Wbiv). This approach was also applied tothe prediction of CLu/F for 10 Parke-Davis compounds. Human oralt1/2, Cmax, AUC, and bioavailability were estimated based onallometrically predicted pharmacokinetic (PK) parameters. Results. Human CL and CL/F were more accurately estimated usingunbound drug concentration and the prediction was further improvedwhen BRW was incorporated into the allometric relationship. ForParke-Davis compounds, the predicted human CL and CL/F werewithin 50-200% and 50-220% of the actual values, respectively. Theestimated human oral t1/2, Cmax, and AUC were within 82-220%,56-240%, and 73-190% of the actual values for all 7 compounds,suggesting that human oral PK parameters of those drugs could bereasonably predicted from animal data. Conclusions. Results from the retrospective analysis indicate thatallometric scaling of free concentration could be applied to orallyadministered drugs to gain knowledge of drug disposition in man, and to helpdecision-making at early stages of drug development.
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  • 70
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; recombinant human interleukin-11 ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 71
    ISSN: 1573-904X
    Keywords: (R,S)-Ifosfamide ; R2-, R3-, S2-, S3-DCE-IFF ; iterative-two stage analysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of R- andS-Ifosfamide (IFF), and their respective 2 and 3 N-dechloroethylated (DCE)metabolites (R2-, R3-, S2, S3-DCE-IFF) in cancer patients. Methods. (R,S)-IFF was administered (1.5 g/m2)daily for 5 days in 13 cancer patients. Plasma and urine samples were collectedand analyzed using an enantioselective GC-MS method. An average of 97observations per patient were simultaneously fitted using apharmacokinetic-metabolism (PK-MB) model. A population PK analysis was performedusing an iterative 2-stage method (IT2S). Results. Auto-induction of IFF metabolism was observed over the 5day period. Increases were seen in IFF clearance (R: 4 vs 7 L/h; S: 5vs 10 L/h), and in the formation of DCE (R: 7 vs 9%; S: 14 vs 19%)and active metabolites (4-OHM-IFF; R: 71 vs 77%; S: 67 vs 71%). Anovel finding of this analysis was that the renal excretion of the DCEmetabolites was also induced. Conclusions. This population PK-MB model for (R,S)-IFF may beuseful in the optimization of patient care, and gives new insight intothe metabolism of (R,S)-IFF.
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  • 72
    ISSN: 1573-904X
    Keywords: stealth and remote loading proliposome ; doxorubicin ; pharmacokinetics ; acute toxicity ; anticancer effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of the study was to prepare stealth and remoteloading proliposome (SRP-L) to carry doxorubicin (DXR) and evaluatethe pharmacokinetics, acute toxicity, and anticancer effect of DXRcarried with SRP-L. Methods. SRP-L was transparent solution. When SRP-L was injectedinto 0.9% NaCl aqueous solution containing DXR, liposomes formedand automatically loaded DXR (SRP-L-DXR). The long circulation ofSRP-L-DXR was evaluated using the pharmacokinetics ofSRP-L-DXR, cardiolipin liposomal DXR (CL-DXR) and free DXR (F-DXR).The acute toxicity and anticancer effect of SRP-L-DXR were evaluatedin C57BL/6 mice and murine hystocytoma M5076 tumor model. Results. The average diameter of SRP-L-DXR in pure water was112.9 ± 8.6 (nm) and the encapsulation efficiency of SRP-L-DXRwas 96.5 ± 0.2% in pure water, 95.5 ± 0.1% in 5% glucose and 98.01± 0.6% in 0.9% NaCl. The plasma concentration of SRP-L-DXR wasmuch higher than those of F-DXR and CL-DXR. Compared with thatof F-DXR, the SRP-L-DXR had lower acute toxicity and its anticancereffects depended upon the therapeutic treatment. Conclusions. A novel proliposome (SRP-L) was developed, whichcould automatically load DXR and form SRP-L-DXR with excellentcharacteristics. SRP-L-DXR had lower acute toxicity but was notalways more effective for the treatment of the ascitic M5076 thanF-DXR.
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  • 73
    ISSN: 1573-904X
    Keywords: morphine ; nociceptive effect ; electrical stimulation vocalisation method ; microdialysis ; retrodialysis by drug ; pharmacokinetics ; pharmacodynamics ; modelling ; blood-brain barrier transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To quantify the contribution of distributional processes across the blood-brain barrier (BBB) to the delay in antinociceptive effect of morphine in rats. Methods. Unbound morphine concentrations were monitored in venous blood and in brain extracellular fluid (ECF) using microdialysis (MD) and in arterial blood by regular sampling. Retrodialysis by drug was used for in vivo calibration of the MD probes. Morphine was infused (10 or 40 mg/kg) over 10 min intravenously. Nociception, measured by the electrical stimulation vocalisation method, and blood gas status were determined. Results. The half-life of unbound morphine in striatum was 44 min compared to 30 min in venous and arterial blood (p 〈 0.05). The BBB equilibration of morphine, expressed as the ratio of areas under the curve between striatum and venous blood, was less than unity (0.28 ± 0.09 and 0.22 ± 0.17 for 10 and 40 mg/kg), respectively, indicating active efflux of morphine across the BBB. The concentration-effect relationship exhibited a clear hysterisis with an effect delay half-life of 32 and 5 min based on arterial blood and brain ECF concentrations, respectively. Conclusions. Eighty five percent of the effect delay was caused by morphine transport across the BBB, indicating possible involvement of rate limiting mechanisms at the receptor level or distributional phenomena for the remaining effect delay of 5 min.
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  • 74
    ISSN: 1573-904X
    Keywords: bioequivalence ; dose proportionality ; mixed effects model ; pharmacokinetics ; power model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of this work was a pragmatic, statistically sound and clinically relevant approach to dose-proportionality analyses that is compatible with common study designs. Methods. Statistical estimation is used to derive a (1-α)% confidence interval (CI) for the ratio of dose-normalized, geometric mean values (Rdnm) of a pharmacokinetic variable (PK). An acceptance interval for Rdnm defining the clinically relevant, dose-proportional region is established a priori. Proportionality is declared if the CI for Rdnm is completely contained within the critical region. The approach is illustrated with mixed-effects models based on a power function of the form PK = β0 • Doseβ1; however, the logic holds for other functional forms. Results. It was observed that the dose-proportional region delineated by a power model depends only on the dose ratio. Furthermore, a dose ratio (ρ1) can be calculated such that the CI lies entirely within the pre-specified critical region. A larger ratio (ρ2) may exist such that the CI lies completely outside that region. The approach supports inferences about the PK response that are not constrained to the exact dose levels studied. Conclusion. The proposed method enhances the information from a clinical dose-proportionality study and helps to standardize decision rules.
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  • 75
    ISSN: 1573-904X
    Keywords: SK&F 107647 ; peptide ; pharmacokinetics ; hematore gulatory ; adenocarcinoma ; cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of SK&F 107647, a synthetichematoregulatory peptide, in healthy volunteers and in patientswith adenocarcinoma.Methods. SK&F 107647 pharmacokinetics were evaluated in 2dose-escalation studies. Volunteers received SK&F 107647 as single15-minute iv infusion doses of 1, 10, 100, 500, and 1000 μg/kg. Cancerpatients received 2-hour iv infusions of 0.001, 0.01, 0.1 and 1μg/kg once daily for 10 days. Drug concentrations were quantified in plasmaand urine of healthy volunteers and on days 1 and 10 in plasma ofcancer patients receiving the two top dose levels.Results. In volunteers, mean clearance (CL) ranged from 76.7 to 101ml/hour/kg; mean volume of distribution at steady-state (Vss)rangedfrom 175 to 268 ml/kg. Most of the administered dose was renallyexcreted as intact peptide within 24 hours postinfusion. In patients,mean CL was 57.6 ml/hour/kg, mean Vss ranged from 128 to 150ml/kg and terminal half-life from 2.1 to 3.4 hours. There was littleaccumulation of drug. In both studies, linear pharmacokinetics wasobserved. Clearance approached normal glomerular filtration rate(GFR) in volunteers and correlated with creatinine clearance incancer patients.Conclusions. SK&F 107647 exhibits linear pharmacokinetics, a smallVss, and clearance, primarily renal, approaching normal GFR.
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  • 76
    ISSN: 1573-904X
    Keywords: glycyrrhizic acid ; modeling ; enterohepatic cycling ; PBPK ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To analyze the role of the kinetics of glycyrrhizic acid (GD) in its toxicity. A physiologically-based pharmacokinetic (PBPK) model that has been developed for humans. Methods. The kinetics of GD, which is absorbed as glycyrrhetic acid (GA), were described by a human PBPK model, which is based on a rat model. After rat to human extrapolation, the model was validated on plasma concentration data after ingestion of GA and GD solutions or licorice confectionery, and an additional data derived from the literature. Observed interindividual variability in kinetics was quantified by deriving an optimal set of parameters for each individual. Results. The a-priori defined model successfully forecasted GA kinetics in humans, which is characterized by a second absorption peak in the terminal elimination phase. This peak is subscribed to enterohepatic cycling of GA metabolites. The optimized model explained most of the interindividual variance, observed in the clinical study, and adequately described data from the literature. Conclusions. Preclinical information on GD kinetics could be incorporated in the human PBPK model. Model simulations demonstrate that especially in subjects with prolonged gastrointestinal residence times, GA may accumulate after repeated licorice consumption, thus increasing the health risk of this specific subgroup of individuals.
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  • 77
    ISSN: 1573-904X
    Keywords: luteinising hormone-releasing hormone (LH-RH) antagonist ; cetrorelix ; pharmacokinetics ; population PK/PD-modeling ; testosterone ; rat ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Population models for thepharmacokinetic-pharmacodynamic relationship for cetrorelix (CET), a luteinising hormone-releasinghormone (LH-RH) antagonist, and the pharmacodynamic response ontestosterone production were investigated in rats and dogs. Methods. The plasma concentrations of CET and testosterone weredetermined after intravenous and subcutaneous injections. Thepopulation PK/PD-models were developed using P-PHARM software. Results. Absolute bioavailability of cetrorelix was 100% in rats and97% in dogs. In rats, the pharmacokinetics was explained by atwo-compartment model with saturable absorption, while athree-compartment model was used in dogs. Testosterone suppression in both specieswas described by a sigmoid Emax model with maximum effect (Emax)considered as total hormonal suppression. The duration of testosteronesuppression in rats was longer at higher doses. The populationelimination half-lifes after iv-dose were 3.0 h in rats and 9.3 h in dogs.Population mean estimates of IC50 were 1.39 and 1.24 ng/ml in ratsand dogs, respectively. Conclusions. A population pharmacokinetic model was developed toexplain the dissolution rate limited absorption from the injection site.The suppression of testosterone could be described by an indirectinhibitory sigmoid Emax model. In both species 1-2 ng/ml CET inplasma was necessary to suppress testosterone production.
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  • 78
    ISSN: 1573-904X
    Keywords: methylphenidate ; average bioequivalence ; individual bioequivalence ; human ; pharmacokinetics ; replicated design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine the relative bioavailability of two marketed,immediate-release methylphenidate tablets. The study used a replicatedstudy design to characterize intrasubject variability, and determinebioequivalence using both average and individual bioequivalencecriteria. Methods. A replicated crossover design was employed using 20subjects. Each subject received a single 20 mg dose of the reference tableton two occasions and two doses of the test tablet on two occasions.Blood samples were obtained for 10 hr after dosing, and plasma wasassayed for methylphenidate by GC/MS. Results. The test product was more rapidly dissolved in vitro and morerapidly absorbed in vivo than the reference product. The mean Cmaxand AUC(0 − ∞) differed by 11% and 9%, respectively. Using anaverage bioequivalence criterion, the 90% confidence limits for theLn-transformed Cmax and AUC(0 − ∞), comparing the two replicatesof the test to the reference product, fell within the acceptable range of80–125%. Using an individual bioequivalence criterion the test productfailed to demonstrate equivalence in Cmax to the reference product. Conclusions. The test and reference tablets were bioequivalent usingan average bioequivalence criterion. The intrasubject variability of thegeneric product was greater and the subject-by-formulation interactionvariance was borderline high. For these reasons, the test tablets werenot individually bioequivalent to the reference tablets.
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  • 79
    ISSN: 1573-904X
    Keywords: 1,4-dihydropyridine calcium channel antagonist ; (+)-[3H]PN 200-110 ; senescence-accelerated prone mouse ; brain concentration ; pharmacokinetics ; in vivo receptor binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the in vivo specific binding andpharmacokinetics of a 1,4-dihydropyridine (DHP) calcium channel antagonist, PN200-110, in the senescent brain, using senescence-accelerated pronemice (SAMP8) and senescence-resistant mice (SAMR1). Methods. Blood, brain, and heart samples were taken periodically fromSAMR1 and SAMP8 following intravenous injection of (+)-[3H]PN200-110, and the concentration of (+)-[3H]PN 200-110 in the plasmaand tissues was determined. In addition, the in vivo specific bindingof (+)-[3H]PN 200-110 in the brains of SAMR1 and SAMP8 wasmeasured periodically after intravenous injection of the radioligand. Results. There was very little significant difference between SAMR1and SAMP8 in terms of the half-life (t1/2), total body clearance (CLtot),steady-state volume of distribution (Vdss), and AUC for the plasmaconcentration of (+)-[3H]PN 200-110 after intravenous injection ofthe radioligand. The brain concentration (AUCbrain) for (+)-[3H]PN200-110 and the brain/plasma AUC ratio (AUCbrain/AUCplasma) weresignificantly lower in SAMP8 than in SAMR1, and the heartconcentration (AUCheart) and the heart/plasma AUC ratio (AUCheart/AUCplasma)were similar in both strains. Also, the brain/plasma unbound AUCratio (AUCbrain/AUCplasma-free) for (+)-[3H]PN 200-110 wassignificantly lower in SAMP8 than in SAMR1. The in vivo specific binding(AUCspecific binding, maximal number of binding sites: Bmax) of(+)-[3H]PN 200-110 was significantly lower in brain particulate fractionsof SAMP8 than SAMR1. Conclusions. The concentration and in vivo specific binding of(+)-[3H]PN 200-110 was significantly reduced in the senescent brain. Thesimultaneous analysis of the concentrations of centrally acting drugsand the in vivo specific binding in the brain in relation to theirpharmacokinetics may be valuable in evaluating their CNS effects.
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  • 80
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    Pharmaceutical research 17 (2000), S. 903-905 
    ISSN: 1573-904X
    Keywords: P-glycoprotein ; hepatic metabolism ; pharmacokinetics ; first-pass metabolism ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 81
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    Pharmaceutical research 17 (2000), S. 127-134 
    ISSN: 1573-904X
    Keywords: in-situ head perfusion ; pharmacokinetics ; red blood cells ; water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a viable, single pass rat head perfusion modeluseful for pharmacokinetic studies. Methods. A viable rat head preparation, perfused with MOPS-bufferedRinger's solution, was developed. Radiolabelled markers (red bloodcells, water and sucrose) were injected in a bolus into the internalcarotid artery and collected from the posterior facial vein over 28minutes. The double inverse Gaussian function was used to estimatethe statistical moments of the markers. Results. The viability of the perfusion was up to one hour, with optimalperfusate being 2% bovine serum albumin at 37°C, pH 7.4. Thedistribution volumes for red blood cells, sucrose and water (from all studies,n = 18) were 1.0 ± 0.3ml, 6.4 ± 4.2ml and 18.3 ± 11.9ml, respectively.A high normalised variance for red blood cells (3.1 ± 2.0) suggestsa marked vascular heterogeneity. A higher normalised variance forwater (6.4 ± 3.3) is consistent with additional diffusive/permeabilitylimitations. Conclusions. Analysis of the physiological parameters derived fromthe moments suggested that the kinetics of the markers were consistentwith distribution throughout the head (weight 25g) rather than justthe brain (weight 2g). This model should assist in studying solutepharmacokinetics in the head.
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  • 82
    ISSN: 1573-904X
    Keywords: α1-acid glycoprotein ; protein binding ; dissociation rate ; species difference ; physiological model ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The extremely low clearance and small distribution volumeof UCN-01 in humans could be partly due to the high degree of bindingto hAGP (1,2). The quantitative effects of hAGP on the pharmacokineticsof UCN-01 at several levels of hAGP and UCN-01 were estimatedin rats given an infusion of hAGP to mimic the clinical situation anda physiological model for analysis was developed. Methods. The plasma concentrations of UCN-01 (72.5–7250 nmol/kgiv) in rats given an infusion of hAGP, 15 or 150 nmol/h/kg, weremeasured by HPLC. Pharmacokinetic analysis under conditionsassuming rapid equilibrium of protein binding and incorporating thedissociation rate was conducted. Results. The Vdss and CLtot of UCN-01 (725 nmol/kg iv) in ratsgiven an infusion of hAGP, 150 nmol/h/kg, fell to about 1/250 and 1/700that in control rats. The Vdss and CLtot following 72.5–7250nmol/kg UCN-01 to rats given 150 nmol/h/kg hAGP were 63.9–688ml/kg and 3.18–32.9 ml/h/kg, respectively, indicating non-linearitydue to saturation of UCN-01 binding. The CLtot estimated by thephysiological model assuming rapid equilibrium of UCN-01 bindingto hAGP, was six times higher than the observed value while the CLtotestimated by the model incorporating koff, measured using DCC, wascomparable with the observed value. Conclusions. These results suggest that the slow dissociation ofUCN-01 from hAGP limits its disposition and elimination.
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  • 83
    ISSN: 1573-904X
    Keywords: IVIVC ; racemate ; enantiomers ; metoprolol ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To investigate the ability of an IVIVC developedwith a racemate drug as well as each enantiomer in predicting the invivo enantiomer drug performance. Methods. Dissolution of metoprolol extended releasetablets with different release characteristics (e.g., fast (F),moderate (M), and slow (S)) was performed using USP ApparatusI, pH 1.2, 50 rpm. Metoprolol racemate tablets (S, M, and F, 100 mg) and 50mg oral solution were administered to healthy volunteers, blood samples werecollected over 24 (solution) and 48 (tablet) hours and assayed. IVIVC modelsdeveloped were: (1) Racemate-fraction of drug dissolved (FRD) vsRacemate-fraction of drug absorbed (FRA), (2) R-FRD vs R-FRA, and (3) S-FRDvs S-FRA for combinations of formulations (S/M/F, S/M, S/F, and M/F).Enantiomer Cmax and AUC prediction errors (PEs) were estimated for modelevaluation after convolution of in vivo release rates. Results. The R-IVIVC and S-IVIVC accurately predicted theR- and S-metoprolol pharmacokinetic profiles, respectively. The averagedprediciton errors (PE) for the enantiomer Cmax and AUC were less than10% for S/M/F, M/F, and S/F IVIVC models. Racemate-IVIVC (M/F) wasable to predict S-enantiomer with an average %PE of 2.52 for S-Cmaxand 4.3 for S-AUC. However, the racemate-IVIVC was unable to predict theR-enantiomer pharmacokinetic profile. Conclusions. Metoprolol racemate data cannot be used toaccurately predict R-enantiomer drug concentrations. However, the racematedata was predictive of the active stereoisomer.
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  • 84
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    Annals of biomedical engineering 28 (2000), S. 128-134 
    ISSN: 1573-9686
    Keywords: Hippocampus ; Vigilance states ; Paired-pulse ; Dentate gyrus ; Dentate granule cells ; Evoked response ; Rat ; In vivo studies ; Perforant path ; Maturation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract This study examined the effect of normal development and vigilance state on the modulation of dentate granule cell activity in the freely moving rat at 15, 30, and 90 days of age across three vigilance states: quiet waking, slow-wave sleep, and rapid eye movement sleep. Using paired-pulse stimulation, the paired-pulse index (PPI) was obtained for the dentate evoked field potentials elicited by the stimulation of the medial perforant path. Although significant differences in PPI values were observed during development, no significant vigilance state related changes were obtained. Preweaning infant rats, i.e., 15-day old, exhibited significantly less early (interpulse intervals, IPI= 20–50 ms) and late (IPI = 300–1000 ms) inhibition, and less facilitation (IPI = 50–150 ms) when compared to the 90-day old adult rats during all three vigilance states. PPI values obtained from the 30-day old group fell intermediate between the 15- and 90-day old animals. These changes in PPI values provide a quantitative measure of changes in the modulation of dentate granule cell excitability during normal maturation. They can now can be used to evaluate the impact of various insults, such as prenatal protein malnutrition or neonatal stress, on hippocampal development. © 2000 Biomedical Engineering Society. PAC00: 8717Nn, 8719La, 8719Nn
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  • 85
    ISSN: 1573-9686
    Keywords: Heart ; Left ventricle ; LV contractility ; ESPVR ; Pig ; Rat ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The end systolic pressure–volume relation (ESPVR) has been shown to be a relatively load independent measure of left ventricular (LV) contractility. Recently, several single-beat ESPVR computation methods have been developed, enabling the quantification of LV contractility without the need to alter vascular loading conditions on the heart. Using a single-beat ESPVR method, which has been validated previously in humans and assumes that normalized elastance is constant between individuals of a species, we studied the effects of myocardial infarction on LV contractility in two species, the rat and the pig. In our studies, LV pressure was acquired invasively and LV volume determined noninvasively with magnetic resonance imaging, at one week postinfarction in pigs and at 12 weeks postinfarction in rats. Normalized systolic elastance curves in both animal species were not statistically different from that of humans. Also, the slope of the ESPVR $$\left( {E_{es} } \right)$$ decreased significantly following infarction in both species, while the volume-axis intercept $$\left( {V_0 } \right)$$ was unaffected. These results indicate that a single-beat ESPVR method can be used to measure the inotropic response of the heart to myocardial infarction, and that the basis for this method (i.e., constant normalized elastance) is applicable to a variety of mammalian species. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 8761Lh, 8719Hh, 8719Rr, 8719Ff
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  • 86
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    Annals of biomedical engineering 28 (2000), S. 1101-1115 
    ISSN: 1573-9686
    Keywords: Time–frequency analysis ; Coherence ; Cross correlation ; Nonstationary persistent signals ; Central pattern generator ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract We present a novel time-varying phase spectrum (TVPS) method to quantify the dynamics of coevolution of two persistent nonstationary coupled signals. Based on the TVPS, an instantaneous intersignal phase shift is defined within the primary frequency range in which the two signals are highly correlated. The TVPS is estimated using a fixed-window method or an adaptive-window method. In the latter method, the window length changes dynamically and automatically as a function of change in frequency of the signals. The effects of altering window types and lengths on the accuracy of the estimation of the primary phase shift is assessed by analyzing synthesized linear chirp signals with decaying amplitude and constant relative phase shift or decaying amplitude and changing relative phase shifts. The methods developed are also used for determining the evolution of the primary phase shift among ventral root activities during fictive locomotion in an in vitro rat spinal cord preparation. The analyses indicate that the TVPS method in conjunction with the determination of the primary frequency range, allows determination of both the evolution of the coupling strength and the evolution of the phase shift between two persistent nonstationary rhythmic signals in the joint time–frequency domain. An adaptive window reduces the estimation bias and the estimation variability. © 2000 Biomedical Engineering Society. PAC00: 0230-f, 8780Tq
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  • 87
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    Fish physiology and biochemistry 23 (2000), S. 225-232 
    ISSN: 1573-5168
    Keywords: methylisoborneol ; catfish ; cytochrome P450 ; biotransformation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 2-Methylisoborneol (MIB) and structurally related terpenoid compounds are responsible for millions of dollars of lost revenue to catfish farmers. In an attempt to determine enzymatic pathways of biotransformation and elimination of MIB, the in vitro metabolism of MIB was examined in the Ulvade strain of channel catfish (Ictalurus punctatus). Although cytochrome P450 (CYP) activities were observed and correlated with expression of specific isoforms (i.e. steroid hydroxylation and CYP3A expression), no metabolites of MIB were observed. To determine whether extrahepatic biotransformation may be occurring the in vivo metabolism and disposition of 14C-MIB was examined in Uvalde, USDA-103 channel catfish, and a channel catfish X blue catfish (Ictalurus furcatus) hybrid species. Confirming in vitro hepatic studies, no metabolites were observed in plasma from animals treated with an intra-arterial dose of 14C-MIB. 14C-MIB elimination was predicted using a two compartment model in each strain of fish. There was no significant difference in terminal half-lives between strains but possible differences in total body clearance and apparent volumes of distribution which may be related to higher lipid content in the hybrids. Results of these studies indicate biotransformation has no involvement in MIB elimination and that other physiological processes may play a more significant role in MIB disposition within Ictalurid fish species.
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  • 88
    ISSN: 1573-1561
    Keywords: Insecta ; tobacco hornworm ; Manduca sexta ; tobacco ; Nicotiana tabacum ; ozone ; weather fleck ; Lepidoptera ; Sphingidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Tobacco plants, Nicotiana tabacum were grown under different levels of ozone (O3) in open-top chambers. Ozone concentrations were established by charcoal filtration, which reduced O3 to approximately one-half ambient, or by the addition of O3 to unfiltered air to increase concentrations to approximately 1.4 or 1.7 times ambient O3. Survival of tobacco hornworm, Manduca sexta, larvae was increased when second instars were fed tobacco leaves grown in chambers with elevated levels of O3. Second instars also gained significantly more weight when they were fed for one week on plants exposed to elevated levels of O3 than when they were fed plants grown in charcoal-filtered air. Ozone-treated tobacco plants had higher levels of total nitrogen (primarily reduced nitrogen) and soluble carbohydrates (sugars), and lower levels of leaf-surface components, starch, nicotine, and rutin. Increased survival and growth response of hornworm larvae to elevated O3 levels in these experiments suggests that similar responses could occur in the southeastern US tobacco production areas where O3 levels can be high enough to injure tobacco plants.
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  • 89
    ISSN: 1573-1561
    Keywords: Lepidoptera ; Tortricidae ; Enarmonia formosana ; cherry bark tortrix ; kairomone ; host selection ; foraging behavior ; plant volatiles ; nonhost volatiles ; repellency/inhibition ; oviposition deterrence ; hexanol ; benzyl alcohol ; nonanal ; decanal ; α-pinene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract We tested the hypothesis that males and females of the cherry bark tortrix (CBT), Enarmonia formosana, antennally perceive and behaviorally respond to volatiles from nonhost plants. Volatiles from flowering cherry trees, Prunus serrulata Kwanzan, and from nonhost trees, including trembling aspen, Populus tremuloides, grand fir, Abies grandis, Norway spruce, Picea abies, and Scots pine, Pinus sylvestris, were captured on Porapak Q and extracts analyzed by coupled gas chromatographic–electroantennographic detection (GC-EAD). Compounds that elicited responses from male and female antennae were identified by coupled GC–mass spectrometry (MS) and by comparative GC-MS and GC-EAD with authentic standards. In field cage and field experiments, nonanal from aspen trees and (±)-α-pinene from coniferous trees were effective in reducing captures of male CBT in pheromone-baited traps and deterring oviposition by female CBT on cherry blocks. Recognition of nonhost volatiles, such as nonanal and α-pinene, may allow male and/or female CBT to avoid trees that provide inadequate concealment from predators during calling, resting, and copulation and that are unsuitable for oviposition and development of offspring. Nonhost volatiles may also be exploited for control of CBT by disrupting both mate- and host-finding.
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  • 90
    ISSN: 1573-1561
    Keywords: Field trapping ; pheromone ; Lepidoptera ; Gelechiidae ; Tuta absoluta ; South American tomato moth ; Scrobipalpuloides absoluta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Field evaluations demonstrate that the addition of the minor pheromone component (3E,8Z)-tetradecadien-1-yl acetate to the major component (3E,8Z,11Z)-tetradecatrien-1-yl acetate does not significantly increase the trap catches of Tuta absoluta males in the field. The triene acetate itself is highly attractive, catching about 869 ± 255 males per trap in three consecutive nights. The addition of two isomers of the minor component (3E,8Z)-tetradecadien-1-yl acetate, (3E,11Z)-tetradecadienyl-yl acetate and (8Z,11Z)-tetradecadien-1-yl acetate, to the major component (3E,8Z,11Z)-tetradecatrien-1-yl acetate also did not significantly alter the number of the males caught in the traps.
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  • 91
    ISSN: 1573-1561
    Keywords: Scoliopteryx libatrix ; Noctuidae ; Lepidoptera ; sex pheromone ; methylalkene ; (6Z13)-methylheneicosene ; electroantennogram ; field test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The major component of the female-produced sex pheromone of Scoliopteryx libatrix has been characterized by chemical analysis, synthesis, electrophysiological studies and field tests as (6Z,13)-methylheneicosene, probably the 13S-isomer. This is the first example of a branched chain alkene as a sex pheromone in the Noctuidae and is markedly different from the pheromones of other members of the family. The systematic position of S. libatrix, belonging to a monotypic genus of a one-member subfamily within the Noctuidae, may reflect the unusual structure of the sex pheromone.
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  • 92
    ISSN: 1573-1561
    Keywords: Lepidoptera ; Limacodidae ; Darna trima ; Darna bradleyi ; Setothosea asigna ; Setora nitens ; nettle caterpillars ; oil palm ; sex pheromone ; 2-methylbutyl (E)-7,9-decadienoate ; (E)-2-hexenyl (E)-7,9-decadienoate ; methyl (E)-7,9-decadienoate ; isobutyl (E)-7,9-decadienoate ; (E)-9dodecenal ; (E)-9,11-dodecadienal ; (Z)-9-dodecenal ; (Z)-9,11-dodecadienal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract This study was undertaken to identify sex pheromone components of nettle caterpillars Darna trima and Darna bradleyi (Lepidoptera: Limacodidae) whose larvae defoliate oil palm, Elaeis guineensis, in southeast Asia. Coupled gas chromatographic–electroantennographic detection (GCEAD) analyses of pheromone gland extracts revealed two antennally active compounds produced by female D. trima and two by female D. bradleyi. Molecular structures of these candidate pheromone components were identified by electron-impact and chemical-ionization mass spectrometry; retention-index calculations on DB-5, DB-23, and DB-210 columns; microanalytical treatments, as well as syntheses of "auxilliary" compounds that facilitated identification of the compounds. The compounds from D. trima were 2-methylbutyl (E)-7,9-decadienoate (A) and (E)-2-hexenyl (E)-7,9decadienoate (B); from D. bradleyi we identified methyl (E)-7,9-decadienoate (C), and isobutyl (E)-7,9-decadienoate (D). In field experiments in Malaysia, (S)-2-methylbutyl (E)-7,9-decadienoate (SA) in combination with B proved to be essential and synergistic pheromone components for attraction of male D. trima. (R)-2-Methylbutyl (E)-7,9-decadienoate (RA) had no behavioral activity. Compound D singly attracted male D. bradleyi, but addition of C to D at a 1 : 10 ratio significantly enhanced attractiveness of the bait. Synthetic pheromone blends were more effective trap baits than unmated female moths and could be developed for monitoring populations of D. trima and D. bradleyi in Asian oil palm plantations.
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  • 93
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    Biodiversity and conservation 9 (2000), S. 479-486 
    ISSN: 1572-9710
    Keywords: biodiversity ; butterfly ; Ghana ; insect ; lagoon ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A variety of collection methods were used to inventory the insect diversity of the Muni-Pomadze Ramsar site along the Ghana coastline. A total of 75 butterfly species in five families were collected and identified. Twenty-six percent of the butterfly species were open country species. The butterflies were all typical of the coastal zone and no endangered or narrowly endemic species were recorded. The Muni-Pomadze site was also rich in other insect species (67 insect species belonging to 15 orders) as a result of the diverse terrestrial habitats surrounding the lagoon. Butterfly species composition changed with habitat indicating a fine-grained response by the butterfly communities to habitat changes. Data from long-term monitoring of butterfly communities at Muni-Pomadze could prove useful as indicators of habitat quality.
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  • 94
    ISSN: 0219-1032
    Keywords: c-Fos ; Dopamine ; D1 ; Hippocampus ; Rat ; Synaptic Plasticity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract While dopamine is likely to modulate hippocampal synaptic plasticity, there has been little information about how dopamine affects synaptic transmission in the hippocampus. The expression of IEGs including c-fos has been associated with late phase LTP in the CA1 region of the hippocampus. The induction of c-fos by dopaminergic receptor activation in the rat hippocampus was investigated by using semiquantitative RT-PCR and immuno-cytochemistry. The hippocampal slices which were not treated with dopamine showed little expression of c-fos mRNA. However, the induction of c-fos mRNA was detected as early as 5 min after dopamine treatment, peaked at 60 min, and remained elevated 5 h after treatment. Temporal profiles of increases in c-fos mRNA by R(+)-SKF-38393 (50 μM) and forskolin (50 μM) were similar to that of dopamine. An increase in [cAMP] was observed in dopamine-, SKF-, or forskolin-treated hippocampal slices. By immunocytochemical studies, control hippocampal cells showed little expression of c-Fos immunoreactivity. However, when cells were treated with dopamine, an increase in the expression of c-Fos immunoreactivity was observed after treatment for 2 h. The treatment of hippocampal neurons with R(+)-SKF38393 (50 μM) or forskolin (50 μM) also induced a significant increase in c-Fos expression. These results indicate that the dopamine D1 receptor-mediated cAMP dependant pathway is associated with the expression of c-Fos in the hippocampal neurons. These data are consistent with the possible role of endogenous dopamine on synaptic plasticity via the regulation of gene expression. Furthermore, these results imply that dopamine might control the process of memory storage in the hippocampus through gene expression.
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  • 95
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 17 (2000), S. 1426-1431 
    ISSN: 1573-904X
    Keywords: eplerenone ; selective aldosterone receptor antagonist ; dog ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The present study was conducted to characterize the pharmacokinetics of eplerenone (EP), a selective aldosterone receptor antagonist, and its open lactone ring form in the dog. Methods. Pharmacokinetic studies of EP were conducted in dogs following i.v., oral, and rectal dosing (15 mg/kg) and following intragastric, intraduodenal, intrajejunal, and intracolonic dosing (7.5 mg/kg). Results. After oral administration, the systemic availability of EP was 79.2%. Systemic availabilities following administration via other routes were similar to that following oral administration. The half-life and plasma clearance of EP were 2.21 hr and 0.329 l/kg/hr, respectively. Plasma concentrations of the open lactone ring form were lower than EP concentrations regardless of the route of administration. The C-14 AUC in red blood cells was approximately 64% and 68% of the plasma AUC for i.v. and oral doses. Percentages of the dose excreted as total radioactivity in urine and feces were 54.2% and 40.6%, respectively, after i.v. administration, and 40.7% and 52.3%, respectively, after oral administration. The percentages of the dose excreted in urine and feces as EP were 13.7% and 2.5%, respectively, after i.v. administration, and 2.1% and 4.6% after oral administration, respectively. Approximately 11% and 15% of the doses were excreted as the open form following i.v. and oral doses. Conclusions. EP was rapidly and efficiently absorbed throughout the gastrointestinal tract, resulting in a good systemic availability. The drug did not preferentially accumulate in red blood cells. EP was extensively metabolized; however, first-pass metabolism after oral and rectal administration was minimal. EP and its metabolites appear to be highly excreted in the bile.
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  • 96
    ISSN: 1573-904X
    Keywords: amphotericin B ; liposomes ; pharmacokinetics ; toxicokinetics ; tissue distribution ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Amphotericin B in small, unilamellar liposomes (AmBisome) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures, the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated. Methods. Rats (174/sex) received intravenous AmBisome (1, 4, or 12 mg/kg), dextrose, or empty liposomes for 91 days with a 30-day recovery. Safety (including clinical and microscopic pathology) and toxicokinetics in plasma and tissues were evaluated. Results. Chemical and histopathologic changes demonstrated that the kidneys and liver were the target organs for chronic AmBisome toxicity. Nephrotoxicity was moderate (urean nitrogen [BUN] ≤51 mg/dl; creatinine unchanged). Liposome-related changes (vacuolated macrophages and hypercholesterolemia) were also observed. Although plasma and tissue accumulation was nonlinear and progressive (clearance and volume decreased, half-life increased with dose and time), most toxic changes occurred early, stabilized by the end of dosing, and reversed during recovery. There were no delayed toxicities. Concentrations in liver and spleen greatly exceeded those in plasma; kidney and lung concentrations were similar to those in plasma. Elimination half-lives were 1-4 weeks in all tissues. Conclusions. Despite nonlinear accumulation, AmBisome revealed predictable hepatic and renal toxicities after 91 days, with no new or delayed effects after prolonged treatment at high doses that resulted in plasma levels 〉200 μg/ml and tissue levels 〉3000 μg/g.
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  • 97
    ISSN: 1573-904X
    Keywords: aspergillosis ; pharmacokinetics ; amphotericin B ; biodistribution ; liposomes ; cholesterol hemisuccinate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study compared the biodistribution of two amphotericin B formulations in normal and Aspergillus infected mice. Amphotericin B cholesterol hemisuccinate vesicles (ABCV) which reduces the toxicity of amphotericin B and thereby enhances its therapeutic efficacy in a murine model of aspergillosis was compared with conventional amphotericin B deoxycholate suspension (AmBDOC). Methods. ABCV (12 mg/kg wt) and AmBDOC (2 mg/kg wt) were intravenously administered to normal and A.fumigatus infected mice. The concentration of amphotericin B in plasma and other organs was determined at different time points. Results. It was observed that ABCV had a significantly different pharmacokinetic profile compared to conventional amphotericin B. In comparison to AmBDOC significantly lower levels of amphotericin B were observed in kidneys and plasma, the major target organs of toxicity. Animals receiving ABCV demonstrated high levels of amphotericin B in liver (38% retention till 48 h) and spleen (2.6% retention till 48 h) in comparison to AmBDOC (7.3% and 0.21% retention in liver and spleen respectively till 48 h). Biodistribution studies of ABCV in infected mice demonstrated that there was a moderate enhancement in levels of amphotericin B in liver, spleen, lungs and kidneys as compared to normal mice and the plasma levels were reduced. However, such observations were not made after AmBDOC administration to infected mice except for kidneys in which there was a marked increase in uptake as compared to normal mice. Conclusions. Our results suggest that prolonged retention of high concentrations of ABCV in reticuloendothelial system organs is the reason for its reduced toxicity. Enhanced localization of the drug at the infected site may lead to improvement in therapeutic efficacy.
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  • 98
    ISSN: 1573-904X
    Keywords: oral absorption ; humans ; dogs ; rats ; interspecies scale-up ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To conduct a retrospective evaluation of using dog as ananimal model to study the fraction of oral dose absorbed (F) of 43drugs in humans and to briefly discuss potential factors that mighthave contributed to the observed differences in absorption. Methods. Mean human and dog absorption data obtained under fastedstate of 43 drugs with markedly different physicochemical andpharmacological properties and with mean F values ranging from 0.015 to1.0 were obtained from the literature. Correlation of F values betweenhumans and dogs was studied. Based on the same references, additionalF data for humans and rats were also obtained for 18 drugs. Results. Among the 43 drugs studied, 22 drugs were virtuallycompletely absorbed in both dogs and humans. However, the overallcorrelation was relatively poor (r2 = 0.5123) as compared to the earlier ratvs. human study on 64 drugs (r2 = 0.975). Several drugs showed muchbetter absorption in dogs than in humans. Marked differences in thenonliner absorption profiles between the two species were found forsome drugs. Also, some drugs had much longer Tmax values andprolonged absorption in humans than in dogs that might be theoreticallypredicted. Data on 18 drugs further support great similarity in F betweenhumans and rats reported earlier from our laboratory. Conclusions. Although dog has been commonly employed as ananimal model for studying oral absorption in drug discovery anddevelopment, the present study suggests that one may need to exercise cautionin the interpretation of data obtained. Exact reasons for the observedinterspecies differences in oral absorption remain to be explored.
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  • 99
    ISSN: 1573-904X
    Keywords: benzodiazepines ; pharmacokinetics ; EEG ; operational model of agonism ; receptor binding ; muscimol-induced Cl−uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. A mechanism-based model is applied to analyse adaptivechanges in the pharmacodynamics of benzodiazepines upon chronictreatment in rats. Methods. The pharmacodynamics of midazolam was studied in ratswhich received a constant rate infusion of the drug for 14 days, resultingin a steady-state concentration of 102 ± 8 ng·ml−1. Vehicle treated ratswere used as controls. Concentration-EEG effect data were analysed onbasis of the operational model of agonism. The results were comparedto data obtained in vitro in a brain synaptoneurosomal preparation. Results. The relationship between midazolam concentration and EEGeffect was non-linear. In midazolam pre-treated rats the maximum EEGeffect was reduced by 51 ± 23 μV from the original value of 109 ±15 μV in vehicle treated group. Analysis of this change on basis ofthe operational model of agonism showed that it can be explained bya change in the parameter tissue maximum (Em) rather than efficacy(τ). In the in vitro studies no changes in density, affinity or functionalityof the benzodiazepine receptor were observed. Conclusions. It is concluded that the observed changes in theconcentration-EEG effect relationship of midazolam upon chronic treatmentare unrelated to changes in benzodiazepine receptor function.
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  • 100
    ISSN: 1573-1561
    Keywords: Megalophanes viciella ; Psychidae ; Lepidoptera ; bagworm ; sex pheromone ; 1-methylethyl octanoate ; 2-propyl octanoate ; field tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Extracts obtained by rinsing the thorax and extracts from the tergal sex pheromone gland of females of the bagworm moth, Megalophanes viciella, as well as headspace samples from live animals, were analyzed to reveal the chemical structure of the pheromone. As a result, 1-methylethyl octanoate was established as a main sex pheromone component of this species. This was further confirmed by numerous catches of conspecific males in traps baited with this compound in Bulgaria and Roumania.
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