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  • pharmacokinetics  (2,026)
  • Column liquid chromatography  (1,216)
  • Immunocytochemistry  (856)
  • Drosophila  (741)
  • kinetics  (728)
  • Springer  (5,559)
  • Frontiers Media SA  (6)
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  • 1
    Publication Date: 2024-04-05
    Description: The brain functions within an internal environment that is determined and controlled by morphological structures and cellular mechanisms present at interfaces between the brain and the rest of the body. In vertebrates these interfaces are across cerebral blood vessels (blood-brain barrier) choroid plexuses (blood-cerebrospinal fluid barrier) and pia-arachnoid. There is a CSF-brain barrier in the neuroepithelium lining the ventricular system that is only present in embryos. There is now substantial evidence that many brain barrier mechanisms develop early and that in some cases they are functionally more active and even more specialized compared to adult barriers. Therefore barriers in developing brain should be viewed as adapted appropriately for the growing brain and not, as is still widely believed, immature. Considerable advances in our understanding of these barrier mechanisms have come from studies of the developing brain and invertebrates. A striking aspect, to be highlighted in this special edition, is that many of the molecular mechanisms in these very diverse species are similar despite differences in the cellular composition of the interfaces. This Frontiers Topic comprises articles in three sections: Original studies, Reviews and Myths & Misconceptions. Original articles provide new information on molecular and cellular barrier mechanisms in developing brains of primates, including human embryos (Brøchner et al., Ek et al., Errede et al.), rodents (Bauer et al., Liddelow, Strazielle & Ghersi-Egea, Saunders et al., Whish et al.), chick (Bueno et al.) and zebrafish (Henson et al.) as well as studies in drosophila (Hindle & Bainton, De Salvo et al., Limmer et al.). The Reviews section includes evolutionary perspectives of the blood-brain and blood-CSF barriers (Bueno et al., Bill & Korzh). There are also detailed reviews of the current state of understanding of different interfaces and their functional mechanisms in developing brain (Bauer et al., Strazielle & Gjersi-Egea, Liddelow, Richardson et al., Errede et al., Henson et al., Brøchner et al.) and in invertebrates (Hindle & Bainton, De Salvo et al., Limmer et al). Different aspects of the relationship between properties of the internal environment of the brain and its development are discussed. (Stolp & Molnar, Johansson, Prasongchean et al.). A neglected area, namely barriers over the surface of the brain during development is also covered (Brøchner et al.). Clinically related perspectives on barrier disruption in neonatal stroke are provided by Kratzer et al. and other aspects of dysfunction by Morretti et al. and by Palmeta et al. on the continuing problem of bilirubin toxicity. Progress in this field is hampered by many prevailing myths about barrier function, combined with methodologies that are not always appropriately selected or interpreted. These are covered in the Misconceptions, Myths and Methods section, including historical aspects and discussion of the paracellular pathway, a central dogma of epithelial and endothelial biology (Saunders et al.) and a review of markers used to define brain barrier integrity in development and in pathological conditions (Saunders et al.). Use of inappropriate markers has caused considerable confusion and unreliable interpretation in many published studies. Torbett et al. deal with the complexities of the new field of applying proteomics to understanding blood-brain barrier properties as do Huntley at al. with respect to applying modern high throughput gene expression methods (Huntley et al.). The Editorial summarizes the contributions from all authors. This includes mention of some the main unanswered but answerable questions in the field and what the impediments to progress may be.
    Keywords: RC321-571 ; Q1-390 ; zebra fish ; development ; Influx mechanisms ; Tight Junctions ; Drosophila ; Efflux mechanisms ; blood-CSF barrier ; Choroid Plexus ; Blood-Brain Barrier ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSA Life sciences: general issues::PSAN Neurosciences
    Language: English
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  • 2
    Publication Date: 2024-04-01
    Description: In 2011, the National Institutes of Health (NIH), in collaboration with leaders from the pharmaceutical industry and the academic community, published a white paper describing the emerging discipline of Quantitative Systems Pharmacology (QSP), and recommended the establishment of NIH-supported interdisciplinary research and training programs for QSP. QSP is still in its infancy, but has tremendous potential to change the way we approach biomedical research. QSP is really the integration of two disciplines that have been increasingly useful in biomedical research; “Systems Biology” and “Quantitative Pharmacology”. Systems Biology is the field of biomedical research that seeks to understand the relationships between genes and biologically active molecules to develop qualitative models of these systems; and Quantitative Pharmacology is the field of biomedical research that seeks to use computer aided modeling and simulation to increase our understanding of the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, and to aid in the design of pre-clinical and clinical experiments. The purpose of QSP modeling is to develop quantitative computer models of biological systems and disease processes, and the effects of drug PK and PD on those systems. QSP models allow testing of numerous potential experiments “in-silico” to eliminate those associated with a low probability of success, avoiding the potential costs of evaluating all of those failed experiments in the real world. At the same time, QSP models allow us to develop our understanding of the interaction between drugs and biological systems in a more systematic and rigorous manner. As the need to be more cost-efficient in the use of research funding increases, biomedical researchers will be required to gain the maximum insight from each experiment that is conducted. This need is even more acute in the pharmaceutical industry, where there is tremendous competition to develop innovative therapies in a highly regulated environment, combined with very high research and development (R&D) costs for bringing new drugs to market (~$1.3 billion/drug). Analogous modeling & simulation approaches have been successfully integrated into other disciplines to improve the fundamental understanding of the science and to improve the efficiency of R&D (e.g., physics, engineering, economics, etc.). The biomedical research community has been slow to integrate computer aided modeling & simulation for many reasons: including the perception that biology and pharmacology are “too complex” and “too variable” to be modeled with mathematical equations; a lack of adequate graduate training programs; and the lack of support from government agencies that fund biomedical research. However, there is an active community of researchers in the pharmaceutical industry, the academic community, and government agencies that develop QSP and quantitative systems biology models and apply them both to better characterize and predict drug pharmacology and disease processes; as well as to improve efficiency and productivity in pharmaceutical R&D.
    Keywords: RM1-950 ; Q1-390 ; Pharmacodynamics ; In-silico ; pharmacometrics ; Pharmaceutical R&D ; Computational Biology ; pharmacokinetics ; Quantitative Systems Pharmacology ; Modeling & Simulation ; Multi-scale modeling ; Systems Biology ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKG Pharmacology
    Language: English
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  • 3
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    Frontiers Media SA
    Publication Date: 2024-04-05
    Description: This Frontiers Research Topic on ‘Neural Circuits: Japan’ explores the diversity of neural circuit research occurring across Japan by innovative researchers using cutting-edge approaches. This issue has brought together papers revealing the development, structure, and physiology of neuronal circuits involved in sensory perception, sleep and wakefulness, behavioral selection, and motor command generation in a range of species from the nematode to the primate. Like the USA and Europe, Japan is now making a strong effort to elucidate neural circuit function in diverse organisms by taking advantages of optogenetics and innovative approaches for gene manipulation, traditional physiological and anatomical approaches, and neural pathway-selective inactivation techniques that have recently been developed in Japan.
    Keywords: RC321-571 ; Q1-390 ; Cerebellum ; C. elegans ; Drosophila ; Olfactory Bulb ; Basal Ganglia ; Hypothalamus ; Neocortex ; Hippocampus ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSA Life sciences: general issues::PSAN Neurosciences
    Language: English
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  • 4
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    Frontiers Media SA
    Publication Date: 2024-04-04
    Description: This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact
    Keywords: machine learning ; molecular dynamics computer simulation ; molecular modeling ; intrinsically disordered proteins ; ligand design ; collective variable ; sampling enhancement ; non-linear dimensionality reduction ; kinetics ; thema EDItEUR::P Mathematics and Science::PD Science: general issues
    Language: English
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  • 5
    Publication Date: 2023-12-20
    Description: A link between inflammation and cancer was initially made by Rudolf Virchow back in the 19th century. Nowadays many cancers are considered dependent on inflammatory responses to microbial and damaged-self stimuli and both arms of immunity, innate and adaptive, are playing a role in promoting cancer. Moreover, besides environmental factors, opportunistic pathogens contribute to inflammation and cancer. Nevertheless, microbial influence on chronic disease is sometimes difficult to discern, especially in the context of polymicrobial communities, such as those found in the digestive tract. In this light, model organisms provide important insights into immune and growth signals that promote cancer, and suggest therapies that will selectively target potentially harmful microbes or modulate host responses. A number of review and opinion articles in this series address novel aspects and paradigms of the interactions between the microbiota and the host in relation to inflammation and cancer.
    Keywords: Q1-390 ; RC109-216 ; microbiota ; mouse ; innate immunity ; Drosophila ; diet ; aging ; human ; Hologenome ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general
    Language: English
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  • 6
    Publication Date: 2024-04-05
    Description: Since Erspamer and Boretti, 1951 first described the biogenic amine octopamine in the octopus salivary gland as a molecule with “adrenaline-like” action, decades of extensive studies demonstrated the important role octopamine and its precursor tyramine play in invertebrate physiology and behavior. This book contains the latest original research papers on tyramine/octopamine and their receptors in different neuronal and non-neuronal circuits of insects. 〈/p〉Additonally, this book elucidates in detail the latest research on the function of other biogenic amines and their receptors, such as dopamine and serotonin in insects and mice. The reviews in this book summarize the most recent research on the role of biogenic amines in insect antennae, synaptic development, and behavioral modulation by spontaneous dopamine release in Drosophila. Finally, one perspective paper discusses the evolution of social behavior and biogenic amines. 〈br〉〈br〉We recommend this book for all scholars interested in the latest advanced research on the role of biogenic amines in animal behavior. 〈br〉〈br〉ITS dedicates the topic to her teacher, Plotnikova Svetlana Ivanovna (1922-2013).
    Keywords: RC321-571 ; Q1-390 ; octopamine ; Apis mellifera ; olfactory learning and memory ; serotonin ; G-protein coupled receptors (GPCR) ; type I and II synaptic boutons ; Drosophila ; neural circuits ; tyramine ; dopamine ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSA Life sciences: general issues::PSAN Neurosciences
    Language: English
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Risk analysis 19 (1999), S. 711-726 
    ISSN: 1539-6924
    Keywords: variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure-related parameters and parameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non-cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: •Contact Rate (Breathing rates per body weight; fish consumption per body weight) •Uptake or Absorption as a Fraction of Intake or Contact Rate •General Systemic Availability Net of First Pass Elimination and Dilution via Distribution Volume (e.g., initial blood concentration per mg/kg of uptake) •Systemic Elimination (half life or clearance) •Active Site Concentration per Systemic Blood or Plasma Concentration •Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) •Functional Reserve Capacity–Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process–differences among people in “functional reserve capacity.” This has the implication that relevant information for estimating effective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants that are thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1539-6924
    Keywords: MeHg ; pharmacokinetics ; PBPK model ; variability ; risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract An analysis of the uncertainty in guidelines for the ingestion of methylmercury (MeHg) due to human pharmacokinetic variability was conducted using a physiologically based pharmacokinetic (PBPK) model that describes MeHg kinetics in the pregnant human and fetus. Two alternative derivations of an ingestion guideline for MeHg were considered: the U.S. Environmental Protection Agency reference dose (RfD) of 0.1 μg/kg/day derived from studies of an Iraqi grain poisoning episode, and the Agency for Toxic Substances and Disease Registry chronic oral minimal risk level (MRL) of 0.5 μg/kg/day based on studies of a fish-eating population in the Seychelles Islands. Calculation of an ingestion guideline for MeHg from either of these epidemiological studies requires calculation of a dose conversion factor (DCF) relating a hair mercury concentration to a chronic MeHg ingestion rate. To evaluate the uncertainty in this DCF across the population of U.S. women of child-bearing age, Monte Carlo analyses were performed in which distributions for each of the parameters in the PBPK model were randomly sampled 1000 times. The 1st and 5th percentiles of the resulting distribution of DCFs were a factor of 1.8 and 1.5 below the median, respectively. This estimate of variability is consistent with, but somewhat less than, previous analyses performed with empirical, one-compartment pharmacokinetic models. The use of a consistent factor in both guidelines of 1.5 for pharmacokinetic variability in the DCF, and keeping all other aspects of the derivations unchanged, would result in an RfD of 0.2 μg/kg/day and an MRL of 0.3 μg/kg/day.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nutrition 24 (1985), S. 113-119 
    ISSN: 1436-6215
    Keywords: Chloramphenicol ; pharmacokinetics ; residue ; pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary Residues of Chloramphenicol (CAP) were examined in 24 pigs after intramuscular injection of 30 mg CAP/kg body weight. Two pigs were slaughtered after 3, 6, 12,18, 24, 36 hours, 2, 3, 6, 10, 21 and 30 days, respectively. CAP-concentrations were determined in muscle, blood, urine, liver, kidney, bile, and fat. Methods used were gas-liquid chromatography and radioimmunoassay. Detection limits reached were 1−5 ppb. The concentration-time curves obtained reflected a long elimination phase and allowed only calculation of this half-life. Elimination half-life was estimated to be for muscle, blood and urine 160–170 hours, for kidney 310 and for bile 250 hours. Significant correlations were found to exist between CAP-concentrations in plasma and muscle. It appears that blood would be a good body fluid for monitoring CAP-residues in tissue.
    Notes: Zusammenfassung Zur Untersuchung des Rückstandsverhaltens von Chloramphenicol (CAP) wurden 24 Mastschweine, 24–28 Wochen alt, intramuskulär mit 30 mg CAP/kg Körpergewicht behandelt und je 2 Tiere nach 3, 6, 12, 18, 24, 36 Stunden, 2, 3, 6, 10, 21 und 30 Tagen geschlachtet. Die CAP-Gehalte in Muskulatur, Blut, Urin, Leber, Niere, Galle und Fett wurden gaschromatographisch und radioimmunologisch bestimmt. Die Nachweisgrenze beider Methoden liegt in Abhängigkeit von der Matrix zwischen 1 und 5 ppb. Die erhaltenen Kinetiken weisen eine terminale Elimination auf, deren Halbwertszeiten für Muskulatur, Blut und Urin ca. 160–170 Stunden, für Niere 310 Stunden und für Galle 250 Stunden betragen. Die CAP-Konzentration in Muskulatur und Blut weisen eine signifikante, lineare Korrelation auf. Blutuntersuchungen könnten deshalb als Screening-Methode bei umfangreichen Rückstandskontrollen eingesetzt werden.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nutrition 22 (1983), S. 14-26 
    ISSN: 1436-6215
    Keywords: branched chain α-keto acids ; 4-methyl-2-oxopentanoate, 3-methyl-2-oxopentanoate ; 3-methyl-2-oxobutyrate ; dehydrogenation ; transamination ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Michaelis-Konstanten und Aktivitäten von Dehydrogenasen und Transaminasen der drei verzweigten α-Ketosäuren Keto-Valin, Keto-Leucin und Keto-Isoleucin in Leber, Niere, Skeletmuskel und Gehirn von Ratten werden mitgeteilt. Nach oraler Zufuhr passieren nur 11–22% der Ketosäuren unverändert die Leber. Aus pharmakokinetischen und Resorptions-Untersuchungen erhaltene Blutspiegel an Ketosäuren werden zu den Michaelis-Konstanten in Beziehung gesetzt. Bei den geringen Konzentrationen an Ketosäuren nach oraler Zufuhr kann angenommen werden, daß die oxidativen Prozesse in den nichthepatischen Geweben über die Transaminierung überwiegen. Daten über die Wachstumseffizienz von verzweigtkettigen α-Ketosäuren im Vergleich zu den entsprechenden Aminosäuren stimmen mit dieser Vorstellung überein. Bei intravenöser Verabreichung müßten die Voraussetzungen für Transaminierung besser sein als nach oraler Zufuhr. Auf der Basis von Daten aus der Literatur werden die Übertragbarkeit unserer Befunde auf den Menschen und die verschiedenen Faktoren, welche die Effizienz der verzweigten α-Ketosäuren durch Einwirkung auf ihren Stoffwechsel beeinflussen können, diskutiert.
    Notes: Summary Miehaelis-constants and enzyme activities for dehydrogenation and transamination of the three branched chainα-keto acids in liver, kidney, skeletal muscle, and brain of rats are reported. After oral load only 11–22 % of the keto acids pass the liver unchanged. Blood levels in pharmacokinetic and absorption studies are related to the Michaelis-constants. At the low keto-acid concentrations after oral application, dehydrogenation in the non-hepatic tissues is supposed to prevail over transamination. Data on feed efficiency of branched chain α-keto acids reported in the literature support this view. The chance for transamination is better after intravenous administration. The transferability of our data to humans, and various factors influencing the efficiency of branched chain α-keto acids are discussed in connection with data reported in the literature.
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