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  • pharmacokinetics  (273)
  • growth  (269)
  • Inversion
  • Rat
  • Springer  (601)
  • 3
  • Institut für Meteorologie und Geophysik
  • Wiley
  • 1995-1999  (601)
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  • 1
    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.
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  • 2
    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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  • 3
    Electronic Resource
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    Springer
    Empirical economics 24 (1999), S. 23-44 
    ISSN: 1435-8921
    Keywords: Key words: Cointegration ; convergence ; growth ; Kalman filter ; JEL classifications: C22 ; O47 ; O57
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract. Augmented Dickey Fuller (ADF) and Kalman filter convergence tests are applied to annual GDPs per head to 16 industrialised countries from 1890 to 1989. Results favour convergence towards the US with a structural break following the Second World War. Estimates suggest that steady-states were higher after the war and that speeds of convergence are different across countries. The Kalman filter method dismissed the no convergence hypothesis more often than its ADF counterpart. This could explain the apparent contradiction in earlier empirical work on similar data sets (cross-section methods tended to favour convergence while time series methods were unable to dismiss the no convergence hypothesis.)
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  • 4
    Electronic Resource
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    Springer
    Animal cognition 2 (1999), S. 123-129 
    ISSN: 1435-9456
    Keywords: Key words Face recognition ; Inversion ; Expertise ¶effect ; Matching-to-sample ;  Macaca mulatta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract This study investigated the face inversion effect in rhesus monkeys (Macaca mulatta). Face stimuli consisted of ten black-and-white examples of unfamiliar rhesus monkey faces, brown capuchin faces, and human faces. Two non-face categories included ten examples of automobiles and abstract shapes. All stimuli were presented in a sequential matching-to-sample format using an automated joystick-testing paradigm. Subjects performed significantly better on upright than on inverted presentations of automobiles, rhesus monkey and capuchin faces, but not human faces or abstract shapes. These results are inconsistent with data from humans and chimpanzees that show the inversion effect only for categories of stimuli for which subjects have developed expertise. The inversion effect in rhesus monkeys does not appear to be face-specific, and should therefore not be used as a marker of specialized face processing in this species.
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  • 5
    ISSN: 1572-977X
    Keywords: Avicennia alba ; growth ; internodal sequences ; mangrove age determination ; Rhizophora apiculata ; Sonneratia caseolaris ; Thailand
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The occurrence of periodic changes in the length of the internodes of the seedlings of SE Asian mangrove species (Rhizophora apiculata, Avicennia alba, and Sonneratia caseolaris) growing in the Pak Phanang estuary (Nakhon Si Thammarat, SE Thailand) was confirmed. The annual nature of these periodic changes was verified through comparisons with the observed average number of internodes produced by plants tagged for one year. The cycles in the sequence of internodal length of the seedlings had an average (± SE) period of 16.0 ± 0.78 internodes for Avicennia alba, 25.0 ± 1.2 internodes for Sonneratia caseolaris, and 8.29 ± 0.40 internodes for Rhizophora apiculata. These values are remarkably close to, and not significantly different (t‐test, P 〉 0.05) from the average (± SE) annual number of internodes of 17.6 ± 0.8 for Avicennia alba, 28.8 ± 2.1 for Sonneratia caseolaris, and 8.03 ± 0.36 for Rhizophora apiculata produced in a year by tagged plants. In addition, the average (± SE) growth of the tagged plants was 0.39 ± 0.018 cm day-1 for Avicennia alba, 0.24 ± 0.015 cm day-1 for Sonneratia caseolaris, and 0.091 ± 0.0036 cm day-1 for Rhizophora apiculata. These estimates were very close to those (0.45 ± 0.06 cm day-1 for Avicennia alba, 0.32 ± 0.01 cm day-1 for Sonneratia caseolaris, and 0.13 ± 0.005 cm day-1 for Rhizophora apiculata) derived as the product of the mean number of internodes produced per day, calculated from the inferred number of internodes produced per year, and the mean length of the internodes of the plants. These findings indicate that the use of regular, annual changes in the length of the internodes of mangrove seedlings can be used reliably to determine their age and to estimate their growth rate.
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  • 6
    ISSN: 1432-1211
    Keywords: Key words Class II MHC sequence ; Rat ; Cloning ; RT-PCR ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 7
    ISSN: 1573-143X
    Keywords: bighead carp (Aristichthys nobilis) ; growth ; Laguna Lake ; salinity tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Bighead carp (Aristichthys nobilis Oshima) fry of various ages (11, 18, and 35 days post-hatch) were exposed to the low salinities encountered during the annual intrusion of seawater in Laguna Lake, Philippines. Practical indices of salinity tolerance assessed the effect of a 96 h direct exposure to low salinities (0–16‰). Mean (MST) and median survival times (MST50) of fry decreased as salinity of rearing medium increased. Younger fry were less able to tolerate exposure to these salinities than their older cohorts. Median lethal salinity after 96 h (MLS) revealed higher tolerance among 35–day old fry (7.6‰) than 11 (2.3‰) and 18–day old fry (6.0‰), demonstrating that survival in saline water depends on their age at initial exposure to low salinities. Mean body weight of 18–day old fry reared in 0 and 2‰ for 3 and 4 weeks was higher than for those reared in 4 and 6‰ for the same period. Growth over these periods was inversely related with the range of salinities tested. These results demonstrate that, despite their known stenohalinity, bighead carp fry possess some degree of osmoregulatory capability, allowing them to survive and grow in lakes subjected periodically to saltwater inflow.
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  • 8
    Electronic Resource
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    Springer
    Aquaculture international 7 (1999), S. 287-293 
    ISSN: 1573-143X
    Keywords: bone mineralization ; calcium requirement ; feed efficiency ; growth ; semi-purified diet ; tiger puffer (Takifugu rubripes)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Juvenile tiger puffer (Takifugu rubripes) were fed semi-purified diets with graded levels (0–0.40%) of calcium (Ca) supplements for 8 weeks at a temperature of 23.0–25.5 °C. At the end of the feeding experiment, average final body weight increased with increasing dietary Ca levels. A diet without Ca supplement resulted in poor average final body weight and 0.05% dietary Ca supplement could not significantly improve the growth. However, supplemental Ca levels of 0.10–0.40% significantly increased growth. Dietary Ca supplements of 0.10% or more also improved the feed efficiency in tiger puffer. Ca and phosphorus contents of the bone were independent of dietary Ca supplements. However, 0.40% Ca in the diet decreased the zinc and manganese contents of bone. Results indicated that supplemental Ca levels of 0.10–0.20% in a semi-purified diet were required to maintain normal growth, feed utilization and bone mineralization of tiger puffer.
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  • 9
    ISSN: 1573-4919
    Keywords: NADH oxidase ; protein disulfide-thiol interchange ; dipyridyl-dithio substrates ; plasma membrane ; auxin ; 2,4-dichlorophenoxyacetic acid ; growth ; plant (Glycine max)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Dipyridyl-dithio substrates were cleaved by isolated vesicles of plasma membranes prepared from etiolated hypocotyls of soybean. The cleavage was stimulated by auxins at physiological concentrations. The substrates utilized were principally 2,2′-dithiodippyrine (DTP) and 6,6′-dithiodinicotinic acid (DTNA). The DTP generated 2 moles of 2-pyridinethione whereas the 6,6′-dithiodinicotinic acid generated 2 moles of 6-nicotinylthionine. Both products absorbed at 340 nm. The auxin herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D) stimulated the activity approximately 2-fold to a maximum at about 10 μM. Concentrations of 2,4-D greater than 100 μM inhibited the activity. Indole-3-acetic acid stimulated the activity as well. The growth-inactive auxin, 2,3-dichlorophenoxyacetic acid (2,3-D), was without effect. DTNA cleavage correlated with oxidation of NADH and reduction of protein disulfide bonds reported earlier in terms of location at the external plasma membrane surface, absolute specific activity, pH dependence and auxin specificity. The dipyridyl-dithio substrates provide, for the first time, a direct measure of the disulfide-thiol interchange activity of the protein previously measured only indirectly as an auxin-dependent ability of isolated plasma membrane vesicles to restore activity to scrambled and inactive RNase.
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  • 10
    Electronic Resource
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    Journal of chemical ecology 25 (1999), S. 1455-1479 
    ISSN: 1573-1561
    Keywords: Turnera ulmifolia ; Euptoieta hegesia ; cyanogenesis ; Anolis sagrei ; tritrophic interactions ; host range ; sequestration ; growth ; development ; oviposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract We examine the effects of the cyanogenesis polymorphism in Turnera ulmifolia on larvae, pupae, and adults of Euptoieta hegesia, the most damaging herbivore of T. ulmifolia in terms of tissue loss per unit time. We provide evidence that female E. hegesia do not show preference for host plants on the basis of their cyanogenesis level but do prefer T. ulmifolia over equally cyanogenic, closely related secondary host-plant species (Passiflora sp.). Similarly, cyanogenesis in T. ulmifolia has little effect on the food preference, growth, or development of the larvae. The potential host range of E. hegesia is limited, even within the genus Turnera, but this does not appear to be due to host-plant cyanogenesis. Pupae suffer very high mortality levels in the wild that are not associated with host-plant cyanogenesis, although our studies indicate that larvae are capable of sequestering cyanogenic glycosides from their host plants and possibly of synthesizing these or similar compounds. We provide evidence that the presence of sequestered cyanogenic compounds in the larvae protects them from terrestrial-based predators such as Anolis lizards
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  • 11
    ISSN: 1573-3017
    Keywords: Tubifex tubifex ; sediment bioassay ; hormesis ; growth ; reproduction ; egestion rates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Toxicity assessment based on sediment chronic bioassays with the aquatic worm Tubifex tubifex was performed at ten contaminated sites in the industrial area of Bilbao (Northern Spain). One control and three reference sites were also included. Tubifex bioassay measures both survival and reproduction impairment. These endpoints have been contrasted and discussed in relation to somatic growth and both individual and total biomass of cocoons. Survival was only affected at one site which was heavily contaminated by organic compounds, mainly PAHs. A group of four severely ecotoxic sediments was characterised by a drastic reduction in number and size of cocoons, and adult somatic growth. In other group of sediments, some significant increases were found for these variables. It is suggested that these increases represent an effect of hormesis. An index of reproductive effort was used to integrate the relationship between somatic growth and reproduction. Values of reproductive effort at the test sediments were lower than those at the control sediment, suggesting a conservative strategy of oligochaete worms which consisted in an investment into somatic line (growth) at the expenses of offspring. Rates of food consumption which were estimated from egestion rates, were low at the contaminated sites. This fact could be related to the low production levels found at these sites and may reflect avoidance feeding behaviour of the oligochaete worms within the sediments. At some reference sites, high production could have resulted from high nutritional quality of sediments, or to an hormetic effect due to low concentration of some chemicals. Results are discussed in relation to toxicity data from sediment three-brood bioassay with Daphnia magna Straus performed separately on the same sediments.
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  • 12
    Electronic Resource
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    Cell & tissue research 296 (1999), S. 235-246 
    ISSN: 1432-0878
    Keywords: Key words Transplantation ; Parkinson’s disease ; CNS fetal development ; CNS differentiation ; Neurotrophic factors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have previously shown that a combination of the cytokines interleukin (IL)-1, IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF) can convert rat fetal (E14.5) mesencephalic progenitor cells into tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in vitro. The experiments described here characterize the mesencephalic progenitor cells and their cytokine-induced conversion into dopamine (DA) neurons. For all experiments, we used bromodeoxyuridine (BrdU)-ir cultures of (E14.5) mesencephalic progenitor cells that had been expanded at least 21 days. We first demonstrated that IL-1 induced DA neuron conversion in mesencephalic progenitors, but not in striatal progenitors (P〈0.001). Thus, these cells should be classified as lineage-restricted progenitors, and not omnipotent stem cells. To further characterize cell populations in these cultures, we used monoclonal antibodies against Hu (an early marker for neurons), growth-associated protein (GAP)-43 (a marker for neuronal process extension), TH (a marker for DA neurons), and glial fibrillary acidic protein (GFAP, a marker for astrocytes). We assessed (E14.5) mesencephalic progenitor cell cultures (plated at 125,000 cells/cm2) incubated in the cytokine mixture (described above) or in complete media (CM, negative control). Following 7 days incubation, GFAP-positive cells formed a nearly confluent carpet in both types of cultures. However, numbers of Hu-ir and GAP-43-ir cells in the cytokine-incubated cultures far exceeded those in CM-incubated controls (P=0.0003, P=0.0001, respectively), while numbers of TH-ir cells were 58-fold greater in the cytokine-incubated cultures versus CM-incubated controls. The TH phenotype persisted for 7 days following withdrawal of the differentiation media. Numerous double-labeled cells that were BrdU-ir and also TH-ir, or Hu-ir and also TH-ir, were observed in the cytokine-incubated cultures. These data suggest that cytokines ”drive” the conversion of progenitor cells into DA neurons.
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  • 13
    ISSN: 1432-0878
    Keywords: Key words Subcommissural organ ; Isograft ; Xenograft ; Reissner’s fiber ; Cerebrospinal fluid ; Rat ; Bovine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The subcommissural organ (SCO) secretes glycoproteins into the cerebrospinal fluid (CSF) that aggregate and form Reissner’s fiber (RF). The factors involved in this aggregation are not known. One factor may be the hydrodynamics of the CSF when flowing through the aqueduct. This hypothesis was tested by isografting rat SCO and xenografting bovine SCO into the lateral ventricle of rats. Xenografts were either fresh bovine SCO or explants cultured for 30 days before transplantation. The grafts were investigated by electron microscopy and immunocytochemistry using antibodies against RF glycoproteins, serotonin and the glucose transporter I. Maximal time of transplantation was 43 days for isografts and 14 days for xenografts. The isografts were not reinnervated but were revascularized; they secreted into the ventricle RF glycoproteins that became progressively packed into pre-RF and RF structures identical to those formed by the SCO in situ. RF was confined to the host ventricle and at its distal end the constituent proteins disassembled. Xenografts were neither reinnervated nor revascularized and secreted into the host ventricle a material that never formed an RF. These findings indicate that the CSF factor responsible for the formation of RF is species specific, and that this process does not depend on the hydrodynamics of the CSF. The blood vessels revascularizing the isografted SCO acquired the characteristics of the vessels irrigating the SCO in situ, namely, a tight endothelium displaying glucose transporter I, and a perivascular space containing long-spacing collagen, thus indicating that basal release of glycoproteins may also occur in the grafted SCO.
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  • 14
    ISSN: 1432-0878
    Keywords: Key words Axonal transport ; Purkinje cell ; Organotypic culture ; Microinjection ; Antimitotic drugs ; Cytoskeleton ; Dendritic transport ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Axonal and dendritic transport in single Purkinje neurons of cerebellar slice cultures was quantified as single transport distances. Examination of the cells within a vital tissue was regarded as being an approach to the in situ condition. The Purkinje cells were organotypically integrated in the in vitro tissues and extended long axonal projections connecting synapses to the target neurons. The tracer horseradish peroxidase (HRP) was applied via microinjection to the somata of the Purkinje cells and the injected neurons were incubated thereafter for defined time-intervals. The tracer was transported anterogradely into the neuron processes. The measurements on both the axonal and the dendritic transport of microinjected HRP revealed continuous transportation with increasing times of postincubation. This transport was reduced by the use of microtubule-depolymerizing drugs. The axonal transport of the tracer was either retarded in colchicine-treated cells or continuously reduced for up to 50% in vinblastine-treated neurons. Thus, a correlation of axonal transport to the microtubules was demonstrated. The dendrites were filled with the tracer after 60 min of postincubation. Dendritic transport was reduced by the use of vinblastine, and not significantly by colchicine. The results strongly support the dependence of neuronal transport on microtubules as a component of the cytoskeleton.
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  • 15
    ISSN: 1432-0878
    Keywords: Key words Neurofilament ; Basket cell ; Pinceau ; Golgi apparatus ; Calcium binding protein ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract NCS-1 (neuronal calcium sensor) is a recently characterized member of a highly conserved neuron-specific family of calcium-binding proteins, which also includes frequenin and recoverin. The cellular and subcellular distributions of NCS-1 in the rat nervous system were investigated using light- and electron-microscopic immunohistochemistry. NCS-1 immunoreactivity was localized to neuronal cell bodies and axons throughout the brain and spinal cord but not to glial cells. The most intense labeling was observed in myelinated axons, the axonal ramifications of the basket cell in the cerebellar cortex, and large neurons in the brainstem and pons. These same structures were also characterized by heavy labeling for neurofilament protein, as determined by double-labeling experiments. Most axon terminals were unlabeled or only lightly labeled. The most remarkable subcellular staining occurred in the perikarya where intense labeling was associated with the membranes of the trans saccules of the Golgi apparatus. The widespread distribution of NCS-1 indicates that it may be active in a variety of calcium-dependent neuronal functions, whereas the specific subcellular localization to the Golgi apparatus and neurofilament-rich structures suggests a specialized role in calcium regulated protein trafficking and cytoskeletal interactions.
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  • 16
    ISSN: 1432-0878
    Keywords: Key words Glial cell line-derived neurotrophic factor ; GDNF ; Ret ; GDNFR-α ; Brain-derived neurotrophic factor ; BDNF ; NT-3 ; NT-4 ; trk receptors ; Thyroid tissue ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Levels of mRNA for neurotrophins (brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT-3; neurotrophin 4, NT-4) and their receptors (trkA, trkB, trkC) and for glial cell line-derived neurotrophic factor (GDNF) and its receptors (ret, GDNFR-α) were measured in rat thyroid tissue by ribonuclease protection assays. In thyroid tissue the NT-3 mRNA level was threefold lower and the NT-4 mRNA level sixfold higher than those detected in adult rat hippocampus, while BDNF mRNA was undetectable. Very low levels of mRNA for truncated trkB and trkC receptors and no catalytic trkA, trkB or trkC were found. In conclusion NT-3 and NT-4, but not the corresponding functional receptors, are expressed in the thyroid tissue. Therefore, it is unlikely that these factors serve a direct local autocrine or paracrine function in thyroid cell types, and a target-derived mode of action on neurons innervating the thyroid tissue is suggested. An opposite result has been found for the neurotrophic factor GDNF: thyroid tissue showed a high level of transcripts for the GDNF receptor subunits (GDNFR-α and Ret), while GDNF mRNA was undetectable. The in situ hybridization analysis of GDNFR-α and ret mRNA revealed an interesting difference in the cell distribution of these transcripts: ret mRNA is selectively expressed in a subpopulation of cells scattered in the follicular epithelium and in the interfollicular spaces, while GDNFR-α expression is more homogeneous and widespread, including the more abundant cell type of the thyroid gland: the follicular cell. Double-labeling in situ hybridization/immunocytochemistry experiments, with a specific marker (calcitonin), showed that parafollicular cells express ret but not GDNFR-α. This differential distribution of the GDNF receptor components (GDNFR-α and ret) may reflect a peculiar biological role in intercellular communication in the thyroid gland.
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  • 17
    ISSN: 1432-0878
    Keywords: Key words Water channel protein ; Aquaporin ; AQP5 ; Rat ; Salivary glands ; Immunolocalization ; Secretory stimulation ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Aquaporin-5 (AQP5) is a water channel protein and is considered to play an important role in water movement across the plasma membrane. We raised anti-AQP5 antibody and examined the localization of AQP5 protein in rat salivary and lacrimal glands by immunofluorescence microscopy. AQP5 was found in secretory acinar cells of submandibular, parotid, and sublingual glands, where it was restricted to apical membranes including intercellular secretory canaliculi. In the submandibular gland, abundant AQP5 was also found additionally at the apical membrane of intercalated duct cells. Upon stimulation by isoproterenol, apical staining for AQP5 in parotid acinar cells tended to appear as clusters of dots. These results suggest that AQP5 is one of the candidate molecules responsible for the water movement in the salivary glands.
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  • 18
    ISSN: 1573-5176
    Keywords: agar ; Gracilaria tenuistipitata ; growth ; salinity ; seawater pH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Acclimation responses of the red alga Gracilaria tenuistipitata var. liui collected on the northwest coast of Philippines were determined in laboratory setups and outdoor cultivation tanks in Haifa, Israel. Growth under laboratory conditions was influenced by all three variables studied, namely, temperature (20 or 30 °C), salinity (20, 30 or39‰) and seawater pH (6.5, 7.0, 8.0 or ≥ 9.0). In 250 mL flasks lacking pH control growth was influenced by temperature only at 20 ‰, whereas at 39 ‰, growth rates were similar at 20 or 30 °C. In 500 mL cylinders in which pH was controlled, growth rates were significantly different at a pH of 6.5 and 7.0 for all salinities, with maximal rates occurring in 39 ‰. At pH 8.0, and above, growth rates between salinities were similar and reduced to approximately 50% at a pH of 9.0 compared to rates at a pH of 6.5. Photosynthesis responses generally resembled growth responses both, in 250 mL and 500 mL cultures. In 40-L outdoor tanks, weekly growth and agar yields were apparently enhanced by increasing light intensities (up to full sunlight) and nutrient concentrations (up to 0.2 mM PO3 2- and 2.0 mM NH4 +), and rates averaged four times higher than rates determined in the smaller flask cultures. This study shows broad salinity tolerance of G. tenuistipitata var. liui and its ability to sustain growth rates that are among the highest measured for Gracilaria spp. in outdoor cultures.
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  • 19
    ISSN: 1573-5125
    Keywords: eutrophication ; feeding ; growth ; Mytilus edulis ; validation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract EMMY is an ecophysiological model of the growth and reproduction of a single mussel (Mytilus edulis L.). It contains feedback loops in the uptake and metabolism of food and in the partitioning of carbon and nitrogen to the internal state variables somatic tissue, storage, organic shell matrix and gametes. In this paper EMMY is used to simulate individual mussel growth in a series of mesocosm experiments with different inorganic nutrient loads (N and P). The experiments explore the impact of eutrophication reduction scenarios on mussel growth under defined and controlled conditions. In earlier studies EMMY was calibrated using expert knowledge on growth and reproduction during a period of 5 years. The resulting calibrated model was validated for system inputs and observations of three ecosystems with significantly different food and silt concentrations. EMMY reproduced the mussel growth sufficiently accurate in ecosystems with moderate or high food concentrations. In this study EMMY was adapted in order to cope with low food concentrations, then recalibrated (using the original calibration data and procedure) and applied without further calibration to 3 replicated mesocosm experiments. The EMMY simulations in this study show the ecophysiological response of mussels to different food (phytoplankton and detritus) concentrations. It is concluded that the mussels can adapt to significantly reduced food concentrations, due to inorganic nutrient load reduction, and still maintain growth.
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  • 20
    ISSN: 1573-0646
    Keywords: pharmacokinetics ; capecitabine ; 5-fluorouracil ; phase I trials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract An excretion balance and pharmacokinetic study was conducted in cancer patients with solid tumors who received a single oral dose of capecitabine of 2000 mg including 50 μ Ci of 14C-radiolabelled capecitabine. Blood, urine and fecal samples were collected until radioactive counts had fallen to below 50 dpm/mL in urine, and levels of intact drug and its metabolites were measured in plasma and urine by LC/MS-MS (mass spectrometry) and 19F-NMR (nuclear magnetic resonance) respectively. Based on the results of the 6 eligible patients enrolled, the dose was almost completely recovered in the urine (mean 95.5%, range 86–104% based on radioactivity measurements) over a period of 7 days after drug administration. Of this, 84% (range 71–95) was recovered in the first 12 hours. Over this time period, 2.64% (0.69–7.0) was collected in the feces. Over a collection period of 24–48h, a total of 84.2% (range 80–95) was recovered in the urine as the sum of the parent drug and measured metabolites (5′-DFCR, 5′-DFUR, 5-FU, FUH2, FUPA, FBAL). Based on the radioactivity measurements of drug-related material, absorption is rapid (tmax 0.25–1.5 hours) followed by a rapid biphasic decline. The parent drug is rapidly converted to 5-FU, which is present in low levels due to the rapid metabolism to FBAL, which has the longest half-life. There is a good correlation between the levels of radioactivity in the plasma and the levels of intact drug and the metabolites, suggesting that these represent the most abundant metabolites of capecitabine. The absorption of capecitabine is rapid and almost complete. The excretion of the intact drug and its metabolites is rapid and almost exclusively in the urine.
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  • 21
    ISSN: 1573-0646
    Keywords: docetaxel ; plasma assay ; clinical trials ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have developed a specific and sensitive method aiming atdocetaxel (Taxotere®) determination in plasma of treatedpatients. This involved solid-phase extraction of 1 ml of plasmaonto carboxylic acid (CBA) grafted silica cartridges followed byreversed-phase liquid chromatography with UV detection. The bestselectivity was obtained through the use of C18 Uptisphere® asstationary phase. The low limit of quantitation obtained (LOQ:5 ng/ml) allowed measurements of docetaxel up to 24 hours afterone-hour infusions with low dosages of drug (60 mg/m2). Themethod was applied successfully to monitor docetaxel plasma levelswithin two protocols associating fixed dosages of either methotrexate or gemcitabine with escalating doses of Taxotere®.
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  • 22
    ISSN: 1573-0778
    Keywords: batch culture ; conditioned medium ; growth ; hybridoma ; inoculum ; protein productivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Apart from gas concentrations, temperature, and pH, generally only the initial conditions can be manipulated in batch culture. Inoculum size and initial conditioned medium concentration represent two important considerations for optimal batch production. Two hybridoma cell lines were used to assess the impact of these initial conditions on population growth and monoclonal antibody productivity in suspension batch culture. Varying initial cell concentration over the range of 1.0 × 105 cells mL-1 to 3.0 × 105 cells mL-1 did not affect maximum product titre or maximum volumetric cell-hours attained. Initial percent of conditioned medium up to 40 percent strongly impacted on population growth and productivity, with initial levels of 30 to 40% conditioned medium reducing or eliminating lag phase and increasing average viable cell density. However, specific productivity and product titre declined with increasing initial percent conditioned medium, even on a per volume of fresh medium basis. Glutamine and glucose depletion or ammonia toxicity could cause depressed product titres when conditioned medium is used. Glutamine and glucose levels can easily be replenished in conditioned medium at minimal cost, and ammonia can be removed. Specific productivity was higher during cyclic batch operating mode than during batch operating mode. This may be because cyclic batch operating mode results in an incidental volume of conditioned medium at the beginning of each cycle. A two stage, cyclic-batch/batch operating mode can be employed to fully utilize medium and maximize product titre.
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  • 23
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    Journal of applied phycology 11 (1999), S. 293-299 
    ISSN: 1573-5176
    Keywords: organismic determinants ; Gracilaria gracilis ; Rhodophyta ; regeneration ; growth ; mariculture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The growth of Gracilaria gracilis (Stackhouse) Steentoft, Irvine et Farnham was examined by studying the effect of organismic determinants such as thallus length, position along the thallus and branching. Knowledge of these factors is essential in order to increase production from suspended seaweed rafts seeded with vegetative G. gracilis fragments. Seeding netlons with seaweed material freshly collected from subtidal populations provided up to 30% higher relative growth rates than seaweed maintained on the netlons for successive months. Initial seedstock length greatly affected growth rates and yields such that 30-cm thalli fragments resulted in growth rates 14% higher than for 10-cm fragments. This difference is suggested to be due to the higher contribution to overall biomass by growth of lateral branches. Comparisons of the growth of apical and basal fragments suggest that growth takes place over the entire length of the thallus, but that the apex contributes more to overall elongation than does the proximal part. The removal of apical meristems resulted in an enhanced branching frequency with production of four times as many branches as intact fragments. Evidence is also provided for extensive morphological differentiation following long periods of rapid growth. These thalli have very high frequency of branching, are hollow due to the disintegration of medullary cells and are considered to be completely senescent. These factors have implications for the successful cultivation of G. gracilis on commercial mariculture systems.
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  • 24
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    Journal of applied phycology 11 (1999), S. 551-558 
    ISSN: 1573-5176
    Keywords: Nodularia ; growth ; hepatotoxin production ; nodularin ; salinity ; irradiance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The objective of this work was to determine the influence of total dissolved solids/salinity (TDS mgL-1) on growth and biomass specific rates of nodularin (hepatotoxin) production by Nodularia spumigena 001E isolated from Lake Alexandrina, South Australia. Maximum biomass yield (dry matter, chlorophyll a and particulate organic carbon/POC) at 80 μmol photon m-2 s-1 was recorded at 3300 mg TDS L-1 and decreased at salinities above or below this value (p 〈 0.05). The maximum biomass yield (dry matter and chlorophyll a) at 30 μmol m-2 s-1 occurred at a higher salinity of 9900 mg TDS L-1. Cultures grown at 80 μmol m-2 s-1, at a TDS〉 6600 mg L-1, had significantly (p 〈 0.05) lower nodularin content (ml-1 medium) than cultures grown at the same salinities at 30 μmolm-2 s-1. The maximum total toxin concentration (mL-1 medium) occurred at 9900 and 3300 mg TDS L-1 at 30 μmol m-2 s-1and 80 μmol m-2 s-1 respectively. Toxin per unit biomass, expressed as dry matter, chlorophyll a and POC was similar for cultures grown at 30 μmol m-2 s-1 or 80 μmol m-2s-1 at salinities 〈 6600 mg TDS L-1. At salinities 〉 9900 mg TDS L-1 the toxin content per unit biomass decreased at both irradiances, however, cultures grown at 30 μmol m-2s-1 had a higher toxin content than those grown at 80 μmol m-2 s-1. The results indicate that not only do changes in irradiance and salinity directly influence growth and toxin production but that changes in irradiance affected the influence of salinity.
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  • 25
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; pharmacodynamics ; effect compartment model ; indirect response ; sigmoid E max ; tiagabine ; GABA uptake inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Pharmacological inhibition of GABA uptake transporters provides a mechanism for increasing GABAergic transmission, which may be useful in the treatment of various neurological disorders. The purpose of our investigations was to develop an integrated pharmacokinetic–pharmacodynamic (PK/PD) model for the characterization of the pharmacological effect of tiagabine, R-N-(4,4-di-(3-methylthien-2-yl)but-3-enyl)nipecotic acid, in individual rats in vivo. The tiagabine-induced increase in the amplitude of the EEG 11.5–30 Hz frequency band (β), was used as pharmacodynamic endpoint. Chronically instrumented male Wistar rats were randomly allocated to four groups which received an infusion of 3, 10, or 30 mg kg −1 $$(\bar x \pm SE,{\text{ }}n = 23)$$ $$96 \pm 9$$ ml min -1 kg−1, 1.5ŷ0.1 L kg−1 and 20ŷ0.2 min.A time delay was observed between the occurrence of maximum plasma drug concentrations and maximal response. A physiological PK/PD model has been used to account for this time delay, in which a biophase was postulated to account for tiagabine available to the GABA uptake carriers in the synaptic cleft and the increase in EEG effect was considered an indirect response due to inhibition of GABA uptake carriers. The population values for the pharmacodynamic parameters characterizing the delay in pharmacological response relative to plasma concentrations were keo=0.030 min −1 and kout=81 min−1, respectively. Because of the large difference in these values the PK/PD model was simplified to the effect compartment model. Population estimates $$(\bar x \pm SE)$$ were E0=155 ŷ 6 μV, Emax=100 ŷ 5 μV, EC50=287 ŷ 7 ng ml−1, Hill factor=1.8 ŷ 0.2 and keo=0.030 ŷ 0.002 min −1. The results of this analysis show that for tiagabine the combined “effect compartment-indirect response” model can be simplified to the classical “effect compartment” model.
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  • 26
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    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 491-512 
    ISSN: 1573-8744
    Keywords: muscle relaxants ; peripheral elimination ; pharmacokinetics ; peripheral concentrations ; volume of distribution ; pharmacokinetic model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract For anesthetic drugs undergoing nonorgan-based elimination, there is a definite trend towards using pharmacokinetic (PK) models in which elimination can occur from both central (k10 ) and peripheral compartments(k20 ). As the latter cannot be assessed directly, assumptions have to be made regarding its value. The primary purpose of this paper is to evaluate the impact of assuming various degrees of peripheral elimination on the estimation of PK parameters. For doing so, an explanatory model is presented where previously published data from our laboratory on three muscle relaxants, i.e., atracurium, doxacurium, and mivacurium, are used for simulations. The mathematical aspects for this explanatory model as well as for two specific applications are detailed. Our simulations show that muscle relaxants having a short elimination half-life are more affected by the presence of peripheral elimination as their distribution phase occupies the major proportion of their total area under the curve. Changes in the exit site dependent PK parameters (Vdss ) are also mostly significant when k20 is smaller than k10 . Although the physiological processes that determine drug distribution and those affecting peripheral elimination are independent, the two are mathematically tied together in the two-compartment model with both central and peripheral elimination. It follows that, as greater importance is given to k20 , the rate of transfer from the central compartment (k12 ) increases. However, as a result of a proportional increase in the volume of the peripheral compartment, peripheral concentrations remain unchanged whether or not peripheral elimination is assumed. These findings point out the limitations of compartmental analysis when peripheral elimination cannot be measured directly.
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  • 27
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    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 325-328 
    ISSN: 1573-8744
    Keywords: anesthetic techniques ; continuous infusion ; pharmacokinetics
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    Topics: Chemistry and Pharmacology
    Notes: Abstract We have previously described a method of rapidly obtaining a specified steady-state plasma concentration of an intravenous drug within precise limits. However the method is limited to drugs whose disposition may be characterized by an open two-compartment system. In this paper, we illustrate how the method can be extended to drugs whose disposition may be characterized by a mammillary model with any number of compartments. Refinements of our previous technique are also described.
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  • 28
    ISSN: 1573-8744
    Keywords: psoriasis ; hu1124 ; CD11a ; CD3-positive lymphocytes ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of hu1124, a human anti-CD11a antibody, were investigated in human subjects with psoriasis. CD11a is a subunit of LFA-1, a cell surface molecule involved in T cell mediated immune responses. Subjects received a single dose of 0.03, 0.1, 0.3, 0.6, 1, 2, 3, or 10 mg/kg of hu1124 intravenously over 1–3 hr. Blood samples were collected at selected times from 60 min to 72 days after administration. Plasma samples were assayed for hu1124 by ELISA, and pharmacokinetic analyses were performed on the drug plasma concentrations. As the dose of hu1124 was increased, the clearance decreased from 322 ml/day per kg at 0.1 mg/kg to 6.6 ml/day per kg at 10 mg/kg of hu1124. The plasma hu1124 concentration–time profile suggested that the clearance of hu1124 was saturable above 10 μg/ml. In addition, treatment with hu1124 caused a rapid reduction in the level of CD11a expression on CD3-positive lymphocytes (T cells) to about 25% of pretreatment levels. Regardless of the hu1124 dose administered, cell surface CD11a remained at this reduced level as long as hu1124 was detectable (〉0.025 μg/ml) in the plasma. When hu1124 levels fell below 3 μg/ml, the drug was rapidly cleared from the circulation and expression of CD11a returned to normal within 7–10 days thereafter. In vitro, half-maximal binding of hu1124 to lymphocytes was achieved at about 0.1 μg/ml and saturation required more than 10 μg/ml. One of the receptor-mediated pharmacokinetic/pharmacodynamic models which was developed describes the dynamic interaction of hu1124 binding to CD11a, resulting in the removal of hu1124 from the circulation and reduction of cell surface CD11a. The model accounts for the continually changing number of CD11a molecules available for removing hu1124 from the circulation based on prior exposure of cells expressing CD11a to hu1124. In addition, the model also accounts for saturation of CD11a molecules by hu1124 at drug concentrations of approximately 10 μg/ml, thereby reducing the clearance rate of hu1124 with increasing dose.
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  • 29
    ISSN: 1573-8744
    Keywords: drug–drug interactions ; NPML ; experimental design ; pharmacodynamic variability ; pharmacokinetics ; entropy ; covariate ; second stage model ; controlled trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Population approaches are appealing methods for detecting then assessing drug–drug interactions mainly because they can cope with sparse data and quantify the interindividual pharmacokinetic (PK) and pharmacodynamic (PD) variability. Unfortunately these methods sometime fail to detect interactions expected on biochemical and/or pharmacological basis and the reasons of these false negatives are somewhat unclear. The aim of this paper is firstly to propose a strategy to detect and assess PD drug–drug interactions when performing the analysis with a nonparametric population approach, then to evaluate the influence of some design variates (i.e., number of subjects, individual measurements) and of the PD interindividual variability level on the performances of the suggested strategy. Two interacting drugs A and B are considered, the drug B being supposed to exhibit by itself a pharmacological action of no interest in this work but increasing the A effect. Concentrations of A and B after concomitant administration are simulated as well as the effect under various combinations of design variates and PD variability levels in the context of a controlled trial. Replications of simulated data are then analyzed by the NPML method, the concentration of the drug B being included as a covariate. In a first step, no model relating the latter to each PD parameter is specified and the NPML results are then proceeded graphically, and also by examining the expected reductions of variance and entropy of the estimated PD parameter distribution provided by the covariate. In a further step, a simple second stage model suggested by the graphic approach is introduced, the fixed effect and its associated variance are estimated and a statistical test is then performed to compare this fixed effect to a given value. The performances of our strategy are also compared to those of a non-population-based approach method commonly used for detecting interactions. Our results illustrate the relevance of our strategy in a case where the concentration of one of the two drugs can be included as a covariate and show that an existing interaction can be detected more often than with a usual approach. The prominent role of the interindividual PD variability level and of the two controlled factors is also shown.
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  • 30
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    Water resources management 13 (1999), S. 73-84 
    ISSN: 1573-1650
    Keywords: chlorophyll ; growth ; rice crop ; spectral reflectance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Notes: Abstract Relations among spectral reflectance, chlorophyll ‘a’, and growth of rice plants grown on irrigated light textured soil in a semi arid region are presented here. There was a linear relation between spectral reflectance and rice plant height (r = 0.97), for band 1 (0.45–0.52 μm) reflectance values. On the other hand, in bands 2 (0.52–0.60 μm) and 3 (0.63–0.69 μm), reflectance values decreased until 70 days after planting (DAP) and then increased during the reproductive phase of the crop. The near infrared band 4 (0.76–0.90 μm) showed a maximum reflectance at 59 DAP (panicle initiation stage) and a decline in reflectance thereafter through maturity. The peak value of IR/R ratio was 16.39 at 62 DAP during the early reproductive phase; thereafter, it declines gradually with the maturity of the crop. Chlorophyll ‘a’ concentration was high during early growth (vegetative and early reproductive stages) and decreased during the flowering and maturity stages. The rice plant canopy show a high chlorophyll ‘a’ concentration at 64 and 59 DAP for sites A and B, respectively. Chlorophyll ‘a’ concentration is higher in site A plant canopies than it is in site B during the entire crop cycle. A good inverse correlation (r = 0.91) has been found between chlorophyll ‘a’ and band 1, while the IR/R ratio and the normalised difference vegetation index (NDVI) showed a relationship (r = 0.78) with the chlorophyll ‘a’ concentration during the crop cycle. Band 2, 3 and 4 radiance values show a biphasic linear relationship with chlorophyll ‘a’ concentrations, negative for early growth and positive for flowering and maturity stages. Results indicate that the period between 66 to 70 DAP is most suitable for the assessment of rice crop yield, based on chlorophyll ‘a’ concentration.
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  • 31
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    Aquaculture international 7 (1999), S. 251-260 
    ISSN: 1573-143X
    Keywords: bacterial biofilm ; common carp (Cyprinus carpio) ; growth ; rohu (Labeo rohita) ; Tilapia (Oreochromis mossambicus)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Experiments were conducted to enhance the growth of common carp (Cyprinus carpio), rohu (Labeo rohita) and Mozambique tilapia (Oreochromis mossambicus) through use of sugarcane bagasse as substrate. Bagasse was suspended in water with or without supplementation with fertilizers. Bagasse supplemented with cattle dung and urea favoured higher zooplankton production and significantly (p 〈 0.05) increased fish growth by over 50% compared to bagasse or fertilizers on their own. This higher production of fish is attributed to bacterial biofilm promoted on the substrate which, apart from forming food for zooplankton and fish, contributed to improved water quality by lowering ammonia.
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  • 32
    ISSN: 1573-143X
    Keywords: Convict cichlid (Cichlasoma nigrofasciatum ; environmental UV effects ; growth ; ultraviolet radiation ; UVA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The long term (two generations) effect an enhanced (5%) sub-lethal ultraviolet-A (320–400 nm) irradiation on growth and survival rate of a convict cichlid (Cichlasoma nigrofasciatum is presented. Two UVA irradiated populations (G1-UVA and G2-UVA) and two control populations (G1-control and G2-control) were observed from age 60 to 403 days. The UVA populations were exposed to enhanced UVA irradiation from 4 months of age (G1-UVA and from egg's state (G2-UVA). The specific growth rates (daily weight and length increase) and the condition factors of the populations were not affected by the enhanced UVA, it depended more on the population size. At the adapted temperature range (27–29 °C) the survival rate of those populations was not affected by enhanced UVA. A combined effect of enhanced UVA and increased temperature (31–32 °C) was responsible for a high mortality rate in the GI-UVA. A total of 67% of the G1-UVA population died just within a week of exposure to high temperature.
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  • 33
    ISSN: 1573-143X
    Keywords: body composition ; dietary protein ; fecundity ; gonad maturation ; growth ; Nile tilapia (Oreochromis niloticus)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Six-week-old Nile tilapia (Oreochromis niloticus) fry with an average weight (SD) of 0.51(0.2) g were reared for 140 days on five formulated, isocaloric diets of different protein levels (25, 30, 40 and 45% by dry weight). Fish fed diets of higher protein levels (40 and 45%) showed better growth and feed conversion ratio than those on lower protein levels. Fast-growing fish matured earlier. Maturation rate was affected by the dietary protein levels. Males matured earlier than females: the first mature males were recorded when they were 14 weeks old, whereas the females matured after 18 weeks. In both sexes, mean percentage of mature fish rose with increasing dietary protein level, the percentage of mature males being higher than that of the females. Similarly, the percentage of mature fish rose with the increasing age of fish, with more than 50% males and females mature at the age of 22 and 24 weeks, respectively, the exception being the 25% protein diet fed fish, where the percentage of mature fish was below 50%. In all treatments, spawning was initiated when the fish were 22 weeks old. Smallest size at spawning of males and females was 9.2 cm (13.1 g) and 8.1 cm (8.9 g), respectively, and dietary protein levels influenced the size of fish at first maturity. For both sexes, no difference was found in the gonado-somatic index (GSI) among different treatments. Fecundity increased with increasing dietary protein levels, but significant differences were found only between 40–45% and 25–35% dietary protein levels. The relative fecundity (eggs g−1 female) was higher at the lower dietary protein levels (25–35%) than at the higher dietary protein levels (40–45%). The dietary protein levels did not have any significant influence on the size and weight of mature eggs. The chemical composition of fish and mature ovaries was significantly influenced by the dietary protein level.
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  • 34
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    Aquaculture international 7 (1999), S. 179-187 
    ISSN: 1573-143X
    Keywords: feeding ; growth ; larvae ; micro-algae ; pearl oyster (Pinctada margaritifera L.) ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract This paper reports on an experiment to determine growth and survival of blacklip pearl oyster, Pinctada margaritifera (L.), larvae fed a 1:1 mixture of Isochrysis aff. galbana clone T-ISO and Pavlova salina at six different densities (1, 2, 5, 10, 20 and 30 × 103 cells ml-1. Larval growth and survival were assessed every four days over a 20–day period. Exponential and logistic regression models were fitted to the growth and survival responses, respectively. Overall growth of larvae fed ≥5 × 103 cells ml-1 was significantly greater (p 〉 0.01) than growth of larvae reared at other algal densities. The optimal food ration for maximum larval growth was 20 × 103 cells ml-1, which resulted in larvae with antero-posterior shell length of 230 μm after 20 days. These larvae were significantly larger (p 〉 0.05) than those in all other treatments at the end of the experiment. Survival of larvae fed 0, 1 and 2 × 103 cells ml-1 was significantly lower than that of larvae in all other treatments at the end of 15 days (p 〉 0.01). Maximal survival (8%) over the 20 day period was shown by larvae fed 10 × 103 cells ml-1, while lower survival was shown by larvae fed 2 × 103 cells ml-1 (2%) and 1 × 103 cells ml-1 (0%).
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  • 35
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    Aquaculture international 7 (1999), S. 201-205 
    ISSN: 1573-143X
    Keywords: fingerlings ; growth ; light regimes ; photoperiod ; silver catfish (Rhamdia quelen) ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 36
    ISSN: 1573-143X
    Keywords: gilthead sea bream (Sparus aurata) ; growth ; hybridization ; red porgy (Pagrus pagrus) ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Hybridization between gilthead sea bream, Sparus aurata, and red porgy, Pagrus pagrus, was undertaken and viable hybrids were produced by an artificial hormonal-induced cross. The hybrids, from the cross of female red porgy and male gilthead sea bream (Pp × Sa), survived through the yolk-sac larval stage. The hybrids produced from the cross of female gilthead sea bream and male red porgy (Sa × Pp) presented higher mortality in the larval stage (98.4%) compared to gilthead sea bream (80.0%) and red porgy (92.5%). Afterwards, the Sa × Pp hybrid was compared to the offspring of its parental species under the same rearing conditions (tanks of 500 l capacity, natural light, ambient temperature, self-feeding with commercial feed) in a 40–week experiment. In this comparative study, the Sa × Pp hybrid had intermediate mortality rate (6%), compared to gilthead sea bream (0%) and red porgy (21%). The growth profile of this hybrid resembled the slow growing phases of its parents (red porgy in warm period and gilthead sea bream in cold period). The feed conversion ratio between fish forms was not significantly different (1.54–1.84 in the Sa × Pp hybrid, 1.53–1.56 in the maternal species and 1.33–1.40 in the paternal one). The body weight variation in the Sa × Pp hybrid was quite high (31.7–37.9%), compared to that in gilthead sea bream (19.7–24.7%) and red porgy (18.0–31.3%). With respect to body coloration, the Sa × Pp hybrid was distinguishable and classified into groups of red porgy-like (55.1%), gilthead sea bream-like (40.6%), and intermediate forms (4.3%). The preliminary results of this study proved that the produced Sa × Pp hybrid had too low a performance for aquaculture use, but the interesting consequent hereditary potential could be a useful tool in fish hybridization practice.
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  • 37
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    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 329-338 
    ISSN: 1573-8744
    Keywords: propofol ; anaesthesia ; pharmacokinetics ; compartment models ; effect compartment models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Conventional compartmental pharmacokinetic analysis may provide inaccurate prediction of drug concentrations after rapid iv administration. To examine this, compartment and effect compartment analysis was applied to measured arterial and brain concentrations of propofol in sheep after iv administration at a range of doses and dose rates. Although arterial and brain concentrations were reasonably well fitted to compartmental and effect compartment models for individual doses and dose rates, the structure and parameters of all models differed with changes in both dose and rate of administration. There were large discrepancies between predicted and measured arterial and brain concentrations when these models were used to predict drug concentrations across doses and dose rates. These data support the limitations of this type of modeling in the setting of rapid propofol administration.
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  • 38
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    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 513-529 
    ISSN: 1573-8744
    Keywords: desmopressin ; indirect-response modeling ; overhydration ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The objective of the present study was to investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of desmopressin in healthy male subjects at different levels of overhydration. Also, we examined if an indirect-response model could be related to renal physiology and the pharmacological action of desmopressin. Eight healthy male subjects participated in this open, randomized crossover study with three periods. Each subject was orally water loaded (0 to 20ml·kg −1 body weight) on 3 study days in order to achieve three different levels of hydration. After the initial water load, urine was voided every 15 min and the volumes were measured. To ensure continuous overhydration the subjects replaced their fluid loss with drinking-water. When a steady-state diuresis was achieved after approximately 2 hr, 0.396 μg of desmopressin was administered intravenously as a bolus injection. Blood was sampled and urine was collected at intervals throughout the study day (10 hr). An indirect-response model, where desmopressin was assumed to inhibit the elimination of response, was fit to the urine osmolarity data. There were no statistically significant effects of different levels of hydration, as expressed by urine flow rate at baseline, on the estimates of the PK and PD model parameters. The calculated terminal half-lives of elimination (t1/2 β) ranged between 2.76 and 8.37 hr with an overall mean of 4.36 hr. The overall means of plasma clearance and the volumes of distribution of the central compartment (Vc ) and at steady state (Vss ) were estimated to be 1.34 (SD 0.35) ml·min −1 ·kg −1 , 151 (SD28) ml·kg −1 , and 386 (SD 63) ml·kg −1 , respectively. High urine flow rate, indicating overhydration, produced a diluted urine and thus a low osmolarity at baseline (R0 ). The effect of the urine flow rate on the urine osmolarity at baseline was highly significant (p〈0.0001). The mean values for IC50 and the sigmoidicity factor (γ) were 3.7 (SD 1.2) pg·ml −1 and 13.0 (SD 3.5), respectively. In most cases when there was a high urine flow rate at baseline, the model and the estimated PD parameters could be related to the pharmacological action of desmopressin and renal physiology. Thus, the indirect-response model used in this study offers a mechanistic approach of modeling the effect of desmopressin in overhydrated subjects.
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  • 39
    ISSN: 1573-8744
    Keywords: prediction interval ; pharmacokinetics ; population analysis ; NONMEM ; inverse regression ; immunosuppressives
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Basiliximab is an immunosuppressant chimeric monoclonal antibody directed to the human interleukin-2 receptor α-chain used for prevention of acute rejection episodes in organ transplantation. The minimally effective serum concentration necessary to saturate receptor epitopes in kidney transplant patients is 0.2 μg/ml. To guide dose selection for Phase 3 efficacy trials, a population pharmacostatistical model was fitted to intensively sampled Phase 2 pharmacokinetic data. This served as a basis from which to examine candidate dose regimens with respect to the duration over which receptor-saturating concentrations would be achieved posttransplant. Three prediction methods were assessed: one based on simulations, and two others based on first-order approximation using either inverse regression or inversion of confidence intervals. An 80% prediction interval was generated by each method to evaluate its predictive performance against prospectively collected Phase 3 data in 39 renal transplant patients who received two injections of 20mg basiliximab, one prior to surgery and one on Day 4 posttransplant. All methods provided correct prediction of the duration of receptor-saturating concentration. As anticipated, the best performance was obtained from the simulation method which predicted 30 values in the 80% prediction interval, 19.7–52.7 days. The actually observed 80% interval from the Phase 3 data was 23.7–58.3 days.
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  • 40
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    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 559-575 
    ISSN: 1573-8744
    Keywords: T-helper cells ; trafficking ; rebound ; corticosteroids ; circadian rhythm ; methylprednisolone ; drug interactions ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A physiologic pharmacodynamic model was developed to jointly characterize the effects of corticosteroid treatment on adrenal suppression and T-helper cell trafficking during single and multiple dosing in asthmatic patients. Methylprednisolone (MP), cortisol, and T-helper cell concentrations obtained from a previously published study during single day and 6 days of multiple dosing MP treatment were examined. The formation and disposition kinetics of MP were described with a compartmental model. The biorhythmic profile of basal cortisol secretion rate was analyzed using a recent Fourier approach based on circadian harmonics. A three-compartment loop model was proposed to represent three major T-helper cell pools: blood, extravascular site, and lymph nodes. T-helper cell synthesis and degradation rate constants were obtained from the literature. The suppressive effects of cortisol and MP on T-helper cell concentrations were described with a joint additive inhibition function altering the cell migration rate from lymph nodes to blood. The model adequately described both plasma cortisol profiles and T-helper cells in blood after single and multiple doses of MP. The potency of MP for suppression of cortisol secretion was estimated as IC50 = 0.8 ng/ml. The biorhythmic nature of the basal T-helper cells in blood was well described as under the influence of basal circadian cortisol concentrations with IC50 = 79 ng/ml. The model fitted potency of MP for suppression of T-helper cells was IC50 = 4.6 ng/ml. The observed rebound of T-helper cells in blood can also be described by the proposed model. The rhythm and suppression of plasma cortisol and T-helper cells before and during single and multiple dose MP treatment were adequately described by these extended indirect response models.
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  • 41
    ISSN: 1573-904X
    Keywords: etomidate ; pharmacokinetics ; pharmacodynamics ; rat ; electroencephalogram
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The effect-plasma concentration relationship of etomidate was studied in the rat using electroencephalographic changes as a pharmacodynamic parameter. Methods. Etomidate was infused (50 mg/kg/h) in chronically instrumented rats (n = 6) until isoelectric periods of 5 s or longer were observed in the electroencephalogram (EEG). The EEG was continuously recorded during the experiment and frequent arterial blood samples were taken for determination of etomidate plasma concentrations. The changes observed in the raw EEG signal were quantified using aperiodic analysis in the 2.5−7.5 Hz frequency band. The return of the righting reflex was used as another parameter of anesthesia. Results. A mean dose of 8.58 ± 0.41 mg/kg needed to be infused to reach the end point of 5 s isoelectric EEG. The plasma concentration time profiles were most adequately fitted using a three-exponential model. Systemic clearance, volume of distribution at steady-state and elimination half-life averaged 93 ± 6 ml/min/kg, 4.03 ± 0.24 l/kg and 59.4 ± 10.7 min respectively. The EEG effect-plasma concentration relationship was biphasic exhibiting profound hysteresis. Semi-parametric minimization of this hysteresis revealed an equilibration half-life of 2.65 ± 0.15 min, and the biphasic effect-concentration relationship was characterized nonparametrically by descriptors. The effect-site concentration at the return of the righting reflex was 0.44 ± 0.03 μg/ml. Conclusions. The results of the present study show that the concentration-effect relationship of etomidate can be characterized in individual rats using aperiodic analysis in the 2.5−7.5 Hz frequency band of the EEG. This characterization can be very useful for studying the influence of diseases on the pharmacodynamics of etomidate in vivo.
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  • 42
    ISSN: 1573-904X
    Keywords: bioequivalence ; neural networks ; prediction ; pharmacokinetics ; verapamil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The methodology of predicting the pharmacokinetic parameters (AUC, cmax, tmax) and the assessment of their variability in bioequivalence studies has been developed with the use of artificial neural networks. Methods. The data sets included results of 3 distinct bioequivalence studies of oral verapamil products, involving a total of 98 subjects and 312 drug applications. The modeling process involved building feedforward/backpropagation neural networks. Models for pharmacokinetic parameter prediction were also used for the assessment of their variability and for detecting the most influential variables for selected pharmacokinetic parameters. Variables of input neurons based on logistic parameters of the bioequivalence study, clinical-biochemical parameters, and the physical examination of individuals. Results. The average absolute prediction errors of the neural networks for AUC, cmax, and tmax prediction were: 30.54%, 39.56% and 30.74%, respectively. A sensitivity analysis demonstrated that for verapamil the three most influential variables assigned to input neurons were: total protein concentration, aspartate aminotransferase (AST) levels, and heart-rate for AUC, AST levels, total proteins and alanine aminotransferase (ALT) levels, for cmax, and the presence of food, blood pressure, and body-frame for tmax. Conclusions. The developed methodology could supply inclusion or exclusion criteria for subjects to be included in bioequivalence studies.
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  • 43
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    Pharmaceutical research 16 (1999), S. 1392-1398 
    ISSN: 1573-904X
    Keywords: topical application ; dermal absorption ; cutaneous perfusion ; pharmacokinetics ; binding ; half life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Many compounds are applied to the skin with the aim of targeting deeper underlying tissues. This work sought to define the pharmacokinetics of solutes in tissues below a topical application site in terms of perfusate binding, tissue binding and perfusate flow rate. Methods. The disposition kinetics of diclofenac in a single pass perfused limb preparation after dermal application disposition was studied using dextran and bovine serum albumin (BSA) containing perfusates. A pharmacokinetic model was then developed to relate the tissue retention half lives for diclofenac, diazepam, water, lignocaine and salicylate to their fraction unbound in the tissues, their fraction unbound in the perfusate and the perfusate flow rate. Results. Diclofenac had estimated tissue retention half lives of 18.1 hr and 3.5 hr for the dextran and BSA containing perfusates, respectively. The fraction of diclofenac and other solutes unbound in the tissues correlated with their corresponding fraction unbound in the perfusate. The tissue retention half lives for diclofenac and other solutes could be described in terms of the fraction of solute unbound in the tissues and perfusate, together with the flow rate. Conclusions. The tissue pharmacokinetics of solutes below a topical application are a function of their binding in the tissues, binding in perfusate and local blood flow.
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  • 44
    ISSN: 1573-9104
    Keywords: Bioavailability ; Magnesium ; Hijiki ; Sodium alginate ; Rat ; Wakame
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The bioavailability of magnesium from Wakame and Hijiki, and the effects of alginic acid on absorption of dietary magnesium were examined in five groups of rats fed either control, Wakame, Hijiki, AW (containing the same amount of alginate as in the Wakame) and AH (containing the same amount of alginate as in the Hijiki) diets, and animals fed a low magnesium diet (LMg) (twentieth amount of magnesium in the original mineral mixtures as the control). Food intake and body weight gain were decreased by adding sodium alginate to the diets. A large amount of calcium accumulated only in the kidneys of the rats fed the LMg diet. Serum magnesium concentration decreased only in the LMg group. The magnesium content in the defatted left femurs did not differ between the control and Wakame fed animals and also among the animals eating Wakame, Hijiki and AW diets. The breaking force of the right femurs did not differ among all the groups except the LMg group. The ratio of apparent magnesium absorption (%) of the control, LMg, Wakame, Hijiki, AW and AH groups was 82.2, 72.7, 66.9, 50.8, 69.3 and 54.2 in the first experimental period, and was 75.3, 52.1, 57.7, 46.9, 62.6 and 60.5 in the second experimental period, respectively. It was clear that the bioavailability of magnesium in the Wakame fed rats was higher than in those eating the Hijiki. Large amounts of sodium alginate lowered magnesium absorption from the diet.
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  • 45
    ISSN: 1573-904X
    Keywords: submicron lipid emulsion ; supersaturation ; tirilazad ; venous irritation ; pharmacokinetics ; tissue distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To compare the venous irritation, pharmacokinetics, and tissue distribution of tirilazad in rats after intravenous administration of a submicron lipid emulsion with that of an aqueous solution. Methods. Venous irritation was determined by microscopic evaluation of injury to the lateral tail veins of rats. Pharmacokinetic parameters were determined by following plasma concentrations of drug. Tissue distribution of [14C]-tirilazad was determined by quantitative whole body autoradiography. Results. Single dose injections of tirilazad as an emulsion at doses ranging from 1.52 mg to 13.5 mg were non-irritating whereas the solution was irritating at a dose of 1.3 mg. The pharmacokinetic parameters were not statistically different between the emulsion and the solution (p 〉 0.2) at doses of 6 mg/kg/day and 20 mg/kg/day. However, at 65 mg/kg/day dose, a higher AUC(0,6) (4-fold) and lower Vss (18-fold) and CL(5-fold) were observed for the lipid emulsion as compared to the solution (p 〈 0.05). Tissue distribution showed higher initial concentrations (two fold or more) in most tissues for the solution. These values, however, equilibrated by 4 h and AUC(0,4) differences were less than two fold in most tissues. Conclusions. Formulating tirilazad in the lipid emulsion significantly reduces the venous irritation without changing the pharmacokinetics and tissue distribution at low doses.
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  • 46
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    Pharmaceutical research 16 (1999), S. 587-591 
    ISSN: 1573-904X
    Keywords: quinolones ; pharmacokinetics ; permeability ; tissue binding ; hindlimb
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 47
    ISSN: 1573-904X
    Keywords: C6-glioma ; methotrexate ; microdialysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Establishment of the pharmacokinetic profile of methotrexate (MTX) in the extracellular fluid (ECF) of a brain C6-glioma in rats. Methods. Serial collection of plasma samples and ECF dialysates after i.v. infusion of MTX (50 or 100 mg/kg) for 4 h. HPLC assay. Results. Histological studies revealed the presence of inflammation, edema, necrosis, and hemorrhage in most animals. In vivo recovery (reverse dialysis) was 10.8 ± 5.3%. MTX concentrations in tumor ECF represented about 1−2% of the plasma concentrations. Rapid equilibration between MTX levels in brain tumor ECF and plasma. ECF concentrations almost reached steady-state by the end of the infusion (4 h), then decayed in parallel with those in plasma. Doubling of the dose did not modify MTX pharmacokinetic parameters (t1/2α, t1/2β, MRT, fb, Vd, and CLT), except for a 1.7-fold increase of AUCPlasma and a 3.8-fold increase in AUCECF which resulted in a 2.3-fold increase in penetration (AUCECF/AUCPlasma). In spite of an important interindividual variability, a relationship between MTX concentrations in plasma and tumor ECF could be established from mean pharmacokinetic parameters. Conclusions. High plasma concentrations promote the penetration of MTX into brain tissue. However, free MTX concentrations in tumor ECF remain difficult to predict consistently.
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  • 48
    ISSN: 1573-904X
    Keywords: HI-240 ; nonnucleoside inhibitor ; pharmacokinetics ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The purpose of the present study was to examine the pharmacokinetic features and tissue distribution of N-[2-(2-fluorophenethyl)]-N′-[2-(5-bromopyridyl)]-thiourea (HI-240), a novel non-nucleoside inhibitor of HIV reverse transcriptase with potent anti-viral activity against AZT-sensitive as well as multidrug-resistant HIV-1 strains. Methods. A sensitive and accurate high performance liquid chromatography (HPLC)-based quantitative detection method was established to measure concentrations of HI-240 in pharmacokinetic studies. The plasma concentration-time data were modeled by using the WinNonlin program to estimate the pharmacokinetic parameter values. Results. HI-240 had an elimination half-life of 78.3 ± 2.0 min after i.v. administration and 196.8 ± 3.1 min after i.p. administration. The systemic clearance of HI-240 was 2194 ± 61 ml/h/kg after i.v. administration and 9339 ± 1160 ml/h/kg after i.p. administration. Following i.v. injection, HI-240 rapidly distributed to and accumulated in multiple tissues with particularly high accumulation in adipose tissue, adrenal gland, and uterus+ovary. The concentration of HI-240 in brain tissue was comparable to that in the plasma, indicating that HI-240 easily crosses the blood-brain-barrier. Following i.p. injection, HI-240 was rapidly absorbed with a t1/2ka and a tmax values of less than 10 min. Following oral administration, HI-240 was absorbed with a t1/2ka of 4.2 ±1.1 min and a tmax of 95.1 ± 25.1 min. The intraperitoneal bioavailability was estimated at 23.5%, while the oral bioavailability was only 1%. Conclusions. The HPLC-based accurate and precise analytical detection method and pilot pharmacokinetic studies described herein provide the basis for advanced preclinical pharmacodynamic studies of HI-240. The ability of HI-240 to distribute rapidly and extensively into extravascular compartments and easily cross the blood-brain barrier represent significant pharmacokinetic advantages over AZT.
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  • 49
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; Calphostin C ; HPLC ; perylenequinone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To examine the pharmacokinetic features and metabolism of calphostin C, a naturally occurring perylenequinone with potent antileukemic activity. Methods. HPLC-based quantitative detection methods were used to measure calphostin C levels in lysates of leukemic cells and in plasma of mice treated with calphostin C. The plasma concentration-time data were analyzed using the WinNonlin program. In vitro esterases and a microsome P450 preparation in conjunction with a LC-MS(API-EI) system were used to study the metabolism of calphostin C. Results. An intracellular exposure level (AUC0−6h) of 257 μM·h was achieved after in vitro treatment of NALM-6 cells with calphostin C at a 5 μM final concentration in culture medium. After intraperitoneal (i.p.) injection of a 40 mg/kg nontoxic bolus dose of calphostin C, the estimated Cmax was 2.9 μM, which is higher than the effective in vitro concentration of calphostin C against leukemic cells. Drug absorption after i.p. administration was rapid with an absorption half-life of 24.2 min and the estimated tmax was 63.0 min. Calphostin C was cleared with an elimination half-life of 91.3 min. An inactive and smaller metabolite (calphostin B) was detected in plasma of calphostin C-treated mice with a tmax of 41.3 min. Esterase (but not P450) treatment of calphostin C in vitro yielded an inactive metabolite (calphostin B) of the same size and elution profile. Conclusions. Target plasma calphostin C concentrations of potent antileukemic activity can be reached in mice at nontoxic dose levels. This pilot pharmacokinetic study of calphostin C combined with the availability of the described quantitative HPLC method for its detection in cells and plasma provide the basis for future preclinical evaluation of calphostin C and its potential as an anti-leukemic drug.
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  • 50
    ISSN: 1573-904X
    Keywords: bezafibrate ; hyperlipidemia ; pharmacodynamics ; pharmacokinetics ; sustained release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate the role of different routes and modes of administration of bezafibrate (BZF) on its hypolipidemic activity. We hypothesize that the major sites of BZF action are located presystemically as in other 'gastrointestinal (GI) drugs.' Thus, continuous administration of the drug to the GI tract is expected to augment its efficacy and provides a rationale for an oral sustained release preparation of the drug. Methods. The hypothesis was investigated in three experimentally induced-hyperlipidemia rat models. Models A and B were based on cholesterol-enriched diets and Model C on induced acute hyperlipidemia by triton 225 mg/kg. The pharmacokinetics and the pharmacodynamics of the drug following various modes of administration were examined. Results. In all cases, continuous administration of the drug into the duodenum (IGI) at a dose of 30 mg/kg/day for 3 days (Models A and B) or over 18 hr (Model C) reduced significantly both total cholesterol and triglycerides levels and elevated HDL cholesterol levels in comparison to bolus oral administration of the same dose, as well as in comparison to equivalent intravenous infusion (Model C). Infusion of the drug directly into the portal vein produced an equivalent activity to IGI administration. The pharmacokinetic study showed 100% oral bioavailability, good colonic absorption properties and an indication for an enterohepatic cycle. Conclusions. The results confirm that BZF has a first pass hepatic pharmacodynamic effect. Administration of BZF in a slow release matrix tablet to the rats produced the same magnitude of effect as IGI administration, thus proving the pharmacodynamic rationale for this mode of administration for GI drugs.
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  • 51
    ISSN: 1573-5036
    Keywords: 2 ; 4-D ; germination ; growth ; salinity-tolerance ; seed treatment ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Experiments were conducted under laboratory and greenhouse conditions to study the effect of 2,4-D on rooting and salinity tolerance of wheat. Seeds of one commercial wheat (Inqalab-91) and three salt-tolerant wheat lines (WL-41, WL-359, and WL-1073 developed through wide hybridization) were included in the study. Preliminary and short-term experiments were conducted to determine the level of 2,4-D (administered through seed soaking for 24.5 h. at 25 °C in the dark) at which the maximum number of roots emerged. Under hydroponic conditions, 2,4-D treatment of seeds caused an increase of 60 to 100% in the number of primary roots. The maximum increase in the number of roots was observed in one of the salt tolerant wheat lines (WL-41). The roots appeared in bunches but showed stunted growth at higher levels of 2,4-D. Dry matter accumulation decreased markedly; the effect was more pronounced in Inqalab-91 which is less tolerant to stress than other wheat lines. In all wheat types, allocation of dry matter to roots relative to shoot increased due to 2,4-D treatment. In soil, seeds treated with different levels of 2,4-D showed a germination delay of 1–3 days. Although the number of primary roots increased, 2,4-D treatment caused a decrease in total dry matter accumulation by plants grown for 40 days. In another experiment, conducted under greenhouse conditions, seed germination and growth of seedlings was significantly retarded in saline compared to that in non-saline (normal) soil. Initially, the pace of germination of treated seeds as well as seedling growth was slower in both soils, but after six weeks, the leaf area of seedlings raised from treated seeds was greater than those raised from untreated seeds. Towards maturity, plants arising from treated seeds developed wider and longer flag leaves leading to enhanced yield. Root biomass decreased in saline soil as compared to normal soil. However, 2,4-D treatment caused a substantial increase in root biomass in saline soil and the roots were harder in texture in wheats other than Inqalab-91. Seed treatment with 2,4-D led to a significant improvement in the number of productive tillers, yield of straw and grain, and grain protein content of all wheats grown in saline soil. Plants grown in normal soil did not show any marked effect of seed treatment on grain yield and other agronomic parameters. The four wheats showed substantial differences for different parameters but the salt tolerant wheat lines performed better compared to the commercial variety Inqalab-91.
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  • 52
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    Plant and soil 217 (1999), S. 1-15 
    ISSN: 1573-5036
    Keywords: anchorage ; development ; growth ; root systems ; symmetry ; tree stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The stability of shallowly rooted trees can be strongly influenced by the symmetry of the ‘structural’ system of woody roots. Root systems of forest trees are often markedly asymmetric, and many of the factors affecting symmetry, including root initiation and the growth of primary and woody roots, are poorly understood. The internal and environmental factors that control the development, with respect to symmetry and rigidity, of shallow structural root systems are reviewed and discussed with particular reference to Sitka spruce (Picea sitchensis Bong. Carr.). Areas where there is insufficient knowledge are highlighted. A scheme is proposed that represents the root system as a set of spokes that are variable in number, size and radial distribution. Rigidity can vary between and along each of the spokes. The root system is presented as a zone of competition for assimilates, where allocation to individual roots depends upon their position and local variations in conditions. Factors considered include the production of root primordia of different sizes, effects of soil conditions such as the supply of mineral nutrients and water on growth of primary and woody roots, and the effect of forces caused by wind action on growth of the cambium, giving rise to roots which, in cross section, resemble I- or T-beams, and efficiently resist bending.
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  • 53
    ISSN: 1573-5028
    Keywords: aquaporin ; gene expression ; growth ; Oryza sativa ; plasma membrane intrinsic protein (PIP) ; rice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Membrane intrinsic proteins facilitate movement of small molecules often times functioning as water channels. We have identified two genes from rice which encode proteins with characteristic features of plasma membrane intrinsic proteins (PIP). They possess six membrane-spanning domains, an NPA repeat, overall high sequence homologies and characteristic C- and N-terminal hallmark motifs which allowed assignment of OsPIP1a to the PIP1 subfamily and of OsPIP2a to the PIP2 subfamily. OsPIP1a and OsPIP2a showed similar but not identical expression patterns. The two genes were expressed at higher levels in seedlings than in adult plants and expression in the primary root was regulated by light. In internodes of deepwater rice plants which were induced to grow rapidly by submergence, transcript levels were slightly induced in the intercalary meristem (IM) and slightly reduced in the elongation zone (EZ) after 18 h. In internodes of GA-induced excised stem sections transcript levels transiently declined in the IM and EZ after 1 h and subsequently recovered to elevated levels after 18 h. GA also induced OsPIP expression in non-growing tissue after 18 h. In the IM of submergence-induced stem sections transcript levels remained constitutive. The different growth-promoting treatments showed no direct correlation between growth rate and OsPIP gene expression in dividing or expanding cells. In fact, treatment of excised stem sections with ABA or drought stress induced similar changes in OsPIP expression in the growing zone during the first 6 h as GA did. We conclude that regulation of OsPIP1a and OsPIP2a expression is not primarily controlled by growth. GA-induced growth may however change the water status of cells which in turn results in altered PIP abundance.
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  • 54
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    Plant and soil 216 (1999), S. 93-101 
    ISSN: 1573-5036
    Keywords: Acacia cyanophylla ; endomycorrhizae ; growth ; nutrition ; Rhizobia ; salinity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The behaviour of Acacia cyanophylla Lind. plants submitted to salinity stress was followed in the greenhouse. The plants were associated with indigenous symbiotic microorganisms isolated from the coastal dunes of the Souss-Massa region. A two months period of salinity had a large negative impact on plant growth and acquisition of macro nutrients. However, the study underlined the role of the microbial inoculum for the plant in the achievement of salt tolerance. An isolate of Bradyrhizobium sp., RCM6 (R1), originating from the Massa dunes, was highly efficient in improving growth and nutrition of the A. cyanophylla. Double inoculation with the rhizobia and an endomycorrhizal complex, isolated from the Lamzar dunes had a clear additional positive effect, i.e. the fungi further increased the tolerance of the A. cyanophylla plants to salinity.
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  • 55
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    New forests 18 (1999), S. 301-314 
    ISSN: 1573-5095
    Keywords: chilling stress ; drought stress recovery ; field performance ; growth ; morphology ; nursery culture ; tree nursery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Five week old white spruce [Picea glauca (Moench) Voss] seedlings were placed within controlled-temperature growth chambers, and subjected to one of four periodic, chilling treatments for approximately 16 weeks. The treatments differed in the frequency of 24 hour exposure to 5 °C the seedlings received, and ranged from no chilling (control), to once every two, three or four days. After 25 weeks of growth, the control seedlings were significantly taller than all chilling-exposed seedlings, but stem diameters were similar. Chilling did not affect either needle length or needle density compared to control seedlings. During a water deficit test, frequently chilling-exposed seedlings maintained significantly higher mid-day shoot water potentials under extreme water stress. Re-watering after the drought resulted in all chilling-treated seedlings recovering faster to pre-stress shoot water potential levels than the control seedlings. Measurements of new root growth after 21 days at 10 °C indicated that previous chilling exposure delayed or inhibited new root production.
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  • 56
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    Plant growth regulation 29 (1999), S. 101-112 
    ISSN: 1573-5087
    Keywords: ABA ; cell wall-associated peroxidase ; expansins ; growth ; pH ; XET
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Over the past decade it has become clear that we cannot always explain the observed reduction in leaf expansion rates during drought by measuring the plant's water relations. This has led us to question the possibility of a role for the cell wall and its biochemical machinery in controlling the rate of leaf expansion during drought. However, if we are to reject or modify previous assumptions regarding the control of leaf expansion during drought, then we must offer alternative explanations. This article addresses recent work from this laboratory and in the literature, concerning the involvement of cell wall-enzymes, pH and abscisic acid (ABA) in regulating leaf expansion during water deficit.
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  • 57
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    Hydrobiologia 392 (1999), S. 205-215 
    ISSN: 1573-5117
    Keywords: Dreissena ; hypoxia ; thermal stratification ; survival ; growth ; distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Experiments and field surveys were conducted in Hargus Lake (Ohio, U.S.) to investigate the effect of lake stratification on the survival, growth and distribution of zebra mussels. During the lake stratification period, relatively stable temperature and dissolved oxygen (DO) gradients persisted across the water column, allowing us to examine the chronic effect of hypoxia on zebra mussels. Zebra mussels were incubated in cages and suspended at different depths in the water column at both pelagic (max. depth = 12 m) and littoral (max. depth = 3.5 m) sites from April 18 to September 28, 1994. No mussel survived to the end of the experiment in cages ≥ 5.5 m, whereas the highest survival rate (76%) occurred at 5 m depth where temperature and DO remained fairly stable for at least 3 months. The threshold oxygen level for survival was between 1.0–1.7 mg l-1 when water temperature was at about 17–18 °C. While zebra mussels′ survival rate was not affected under the sublethal hypoxic conditions, their growth was greatly retarded by poor water quality. The field survey showed that the zebra mussels and macrophytes had about the same distribution and their biomasses were positively related. The percentage of mussels in aggregates increased towards their maximum distribution depth. The maximum distribution depth of the naturally occurring zebra mussels was only 2.8 m, whereas the adult mussels could survive the entire stratification period when being artificially placed on the 3.5 m bottom, and young mussels could colonize the 3.5 m bottom if solid substrates were provided. We conclude that lack of substrate, rather than hypoxia, was the limiting factor of zebra mussel distribution above 5 m depth in Hargus Lake.
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    Hydrobiologia 401 (1999), S. 265-277 
    ISSN: 1573-5117
    Keywords: nucleic acids ; fish larvae ; RNA/DNA ; condition ; growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Nucleic acid analysis has provided useful tools to study recent growth and mortality of young fishes and their responses to environmental variability. The ratio of RNA–DNA (R/D) has been shown to respond to changes in feeding conditions and growth after periods as short as 1–3 days in a variety of fish species. The earliest studies used primarily UV-based methods, but most investigators now use more sensitive, fluorometric dye-binding assays to estimate RNA and DNA in individual larvae. These newer methods are very sensitive to procedural details and choice of standards. Analytical methods, normalization and calibration procedures to optimize information obtained from nucleic acid analysis are discussed. We present examples illustrating the technique's utility, and problems encountered when applying nucleic acid-based indices to fish larvae and early juveniles. The wide use of R/D analysis in studies of fish early life stages, together with a proliferation of analytical methods, demands a major intercalibration exercise.
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  • 59
    ISSN: 1573-5117
    Keywords: zebra mussel ; intermittent halogenation ; Dreissena polymorpha ; growth ; settlement ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The effect of intermittent (2–4 h/day) treatments with chlorine or bromine at levels of 0.5 and 1.0 mg/L (total residual oxidant) upon settling and growth of veliger larvae of the zebra mussel, Dreissena polymorpha, was examined in two successive flow-through studies. The work was conducted in a field laboratory which received a constant supply of water from western Lake Erie. Veliger densities in the water at the field site peaked at 530/L, while mussel densities on settling monitors reached 147,100/m2 over the course of the two studies (early July to late September 1991). In Study 1, a 2-h daily treatment with 1.0 mg/L chlorine reduced mussel settling by 91% as compared with controls, although mussel densities of up to 6,000/m2 still occurred. Treatment with 0.5 mg/L chlorine for 4 h/day produced a similar reduction in mussel settling during the second study. Bromine was less effective than chlorine at reducing settling of veligers. Mussels which remained settled in the treatment tanks had growth rates similar to controls, reaching 2–4 mm in length over a 30-day period. The intermittent halogen treatments similarly had no effect on whole body glycogen levels or growth of adult D. polymorpha. The intermittent chlorination regime used may therefore delay, but would not prevent a mussel fouling problem.
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  • 60
    ISSN: 1573-5117
    Keywords: Gracilaria multipartita ; seasonal variation ; growth ; chemical composition ; agar
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The biology and agar composition and properties of Gracilaria multipartita, a common species along the coasts of Morocco, have been studied on samples collected monthly for one year. Growth of the alga was maximum in spring and autumn, and the seaweed partially decayed after its maximum fertility was reached in June and October. The agar content and composition showed seasonal variations. The agar content was maximal in winter (30% dw), and decreased during the growth periods to minima in June and October (25% dw) which also corresponded to the maxima of fertility. The agar composition was characterized by high 6-O-methyl galactose (38–59 mol%) and 3,6 anhydrogalactose (24–39%) contents together with galactose (12.6–25.7 mol%) and sulphate (24–5.0% dw). The gel strength varied between 246 and 511 g cm−2 and increased after alkali treatment to reach a maximum of 880 g cm−2. The gel stre ngth decreased after the alga reached its maxima of fertility, indicating a possible relationship between growth, fertility and agar metabolism. The content and quality of agar from G. multipartita growing in Morocco are suitable for an industrial use of the seaweed for the production of food-grade agar.
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  • 61
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    Environmental biology of fishes 54 (1999), S. 325-336 
    ISSN: 1573-5133
    Keywords: population structure ; reproduction ; growth ; mortality ; fish
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Black seabream, Spondyliosoma cantharus, caught off the Canary Islands is characterized by a protogynous hermaphroditism. The size range of the catches is between 8 and 40 cm, with a main distribution between 16 and 24 cm. The mean length of the individuals shows an increase with increasing depth. Males:females ratio is unbalanced in favour of females (1:2.18). The reproductive season extends from late autumn to mid spring, with a peak in spawning activity in January–February. A dichromatism is found between males and females during the spawning season. Males reach maturity at a larger total length, 22.7 cm (3 years old), than females, 17.3 cm (2 years old). Morphometric relationship between length and mass for the whole population is described by the parameters: a=0.00732, and b=3.24747. Otoliths age readings indicate that the exploited population consists of eleven age groups (0–X years), including a very high proportion of individuals between 2 and 3 years old. The von Bertalanffy growth parameters for the whole population are: L∞=43.35 cm, k=0.24 year−1, and t0=−0.11 year. The rates of total, natural and fishing mortality are 1.36, 0.52 and 0.84 year−1, respectively. The length at first capture is 16.8 cm. The exploitation rate indicates that the stock is overfished.
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  • 62
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    Environmental biology of fishes 55 (1999), S. 215-225 
    ISSN: 1573-5133
    Keywords: gonadosomatic index ; growth ; maturity ; migration ; mortality ; sex ratio ; spawning ; von Bertalanffy growth model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Aspects of the life history of Labeo cylindricus in Lake Chicamba, a man made hydroelectric dam in central Mozambique were investigated. L. cylindricus was found to be a potadrometic, synchronous spawner concentrating in river mouths prior to migrating up flowing rivers in January to spawn. Length-at-(50%)-maturity was attained at a fork length (FL) of 96 mm for males and 98 mm for females, both within their first year of life. The adult sex ratio was found to be female dominated at 1 male:1.63 females. Scales were used to age the species, with two growth checks deposited annually. Growth was rapid and was best described by the von Bertalanffy growth model as L t =224.2(1−e-0.66(r+0.03)) mm FL. A maximum age of 4 years was observed for L. cylindricus with the largest male and female measuring 210 mm FL and 235 mm FL, respectively. The rate of natural mortality was estimated to be extremely high at 1.93 year-1 using length-converted catch curve analysis and is possibly a response to heavy predation by the introduced piscivore Micropterus salmoides.
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  • 63
    ISSN: 1573-5133
    Keywords: reproduction ; spawning ; age ; growth ; vermilion snapper ; Trinidad ; Tobago
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Reproduction and growth of the vermilion snapper, Rhomboplites aurorubens, were studied in Trinidad and Tobago. The smallest individual caught measured 145 mm total length (TL) and all fish appeared to be mature. It was not possible to precisely determine size at first maturity due to the use of macroscopic techniques. The smallest spent male and female measured 181 and 211 mm TL respectively, suggesting a size at first maturity below these sizes. Spawning occurred throughout the year, with a period of peak spawning from about June to November in the rainy season when river runoff increased. Sagittal otolith sections were used for age determination and the opaque ring, which was counted as the annulus, was deposited from January to May in the dry season. A total of 11 age groups between the ages of 2–12 years (155–505 mm total length) were found. The von Bertalanffy growth parameters were: L∞=532 mm, K=0.13 y−1, and t0=−0.17, where L∞ is the asymptotic length, K is the growth coefficient and t0 is the theoretical age at zero length. The relationship between weight (WT) and length (TL) was WT=3.43×10−5 TL2.82. Vermilion snapper in this study area appears to grow slower and attain a smaller asymptotic length, but has a longer lifespan than found in populations in higher latitudes. This may be attributed to different levels of exploitation, which may be higher in the latter areas.
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  • 64
    ISSN: 1573-5168
    Keywords: growth ; mass spectrometry ; 15N-phenylalanine ; protein synthesis ; stable isotope technology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In vivo rates of protein synthesis in fish have predominantly been measured using a single flooding dose injection of a solution containing 3H-Phenylalanine as a tracer. However, use of a radiolabelled tracer restricts the application of this technique to controlled laboratory conditions. In this study, the flooding dose technique was used to successfully measure in vivo rates of protein synthesis in Atlantic salmon (Salmo salar L.) smolts utilising a stable isotope labelled amino acid, L-[15N]-Phenylalanine, as an alternative tracer. Methodologies are presented allowing the 15N enrichment in the free amino acid pool and in body protein to be measured using mass spectrometry. In this study, the fractional rates of protein consumption (kr), synthesis (ks) and growth (kg) of Atlantic salmon smolts (37 ± 1.4 g) were measured as 4.7, 3.3 and 1.6% day−1 respectively. Protein synthesis retention efficiency (kgks) and protein growth efficiency (kgkr)were calculated as 48.5 and 34.0% respectively. The ks, kgks and kgkr values obtained in this study were found to be within the range of values available in the literature for juvenile salmonid fish of a comparable size. The use of L-[15N]-Phenylalanine provides an alternative tracer to radiolabelled amino acids for measuring in vivo rates of protein synthesis in fish using the flooding dose' technique and also allows studies of fish protein metabolism to be carried out in environmentally sensitive (field and laboratory) conditions where the use of radiolabels is prohibited.
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  • 65
    ISSN: 1573-5168
    Keywords: Atlantic salmon ; growth ; individual feed consumption rate ; plasma insulin ; protein synthesis capacity ; trypsin isozymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Growth was found to be associated with the changes of trypsin activity in the pyloric caecal tissues and the level of plasma insulin in Atlantic salmon (Salmo salar L.). A decrease in trypsin activity accompanied by an increase in plasma insulin was detected one month before an enhanced growth was observed. There were significant relationships between weight specific consumption rate, plasma insulin levels and fish growth. The correlation of weight specific consumption rate was higher with growth rate (R2=0.7, p〈0.0001) than with plasma insulin concentration (R2=0.4, p〈0.0001). When the comparison was made between Atlantic salmon carrying and lacking the trypsin variant TRP-2*92, the fish with the variant had lower maintenance ration (p〈0.05), higher capacity for protein synthesis in the white muscle (p〈0.02), and a greater ability to utilize the feed at a restricted ration than the fish without the variant. In Atlantic salmon lacking the variant, both plasma insulin concentrations and growth rates were significantly lower (p〈0.05) in the fish fed 0.5% bw day−1 than those fed 1% bw day−1. Whilst the growth rates of TRP-2*92 salmon fed the different rations became similar one month after similar levels of plasma insulin were observed between them. The TRP-2*92 salmon may be defined as a high protein growth efficiency fish with low protein turnover rate. Genetic variation in trypsin isozyme pattern affects feed utilization, plasma insulin levels and growth in Atlantic salmon.
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    Journal of economic growth 4 (1999), S. 429-445 
    ISSN: 1573-7020
    Keywords: growth ; R&D ; education ; regime shift
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract The role of learning and R&D in economic development is addressed in an endogenous growth model. When human capital is below a threshold level, the model predicts that skills are accumulated as the only growth-generating activity, whereas both innovation activities and learning drive growth above this level. Hence, an endogenous regime shift is triggered when the level of human capital reaches the threshold level because it becomes profitable to innovate.
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  • 67
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    Journal of economic growth 4 (1999), S. 55-80 
    ISSN: 1573-7020
    Keywords: mercantilism ; growth ; taxation ; openness ; familiarity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract Nations close themselves voluntarily to varying degrees. Restrictions on the flow of ideas are difficult to understand, since open countries have higher relative incomes. This article provides an explanation based on the existence of two channels of public finance—traditional and mercantilistic. The latter refers to monopoly creation to provide a stream of government revenue. Strong, profitable monopolies require that the nation be closed to new ideas about technology and organization. The government sets the degree of restriction to balance current mercantilistic revenue with future revenue from traditional sources. The model is supported with numerical simulations and historical illustrations.
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    Journal of economic growth 4 (1999), S. 119-137 
    ISSN: 1573-7020
    Keywords: growth ; technology ; Solow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract Growth accounting breaks down economic growth into components associated with changes in factor inputs and the Solow residual, which reflects technological progress and other elements. After a presentation of the standard model, the analysis considers dual approaches to growth accounting (which considers changes in factor prices rather than quantities), spillover effects and increasing returns, taxes, and multiple types of factor inputs. Later sections place the growth-accounting exercise within the context of two recent strands of endogenous growth theory—varieties-of-products models and quality-ladders models. Within these settings, the Solow residual can be interpreted in terms of measures of the endogenously changing level of technology.
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  • 69
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    Journal of economic growth 4 (1999), S. 305-330 
    ISSN: 1573-7020
    Keywords: growth ; convergence clubs ; poverty trap ; cultural factors ; location
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract This study investigates the sources of heterogeneity across a worldwide set of countries. Unspecified ex ante and unanticipated cultural (Protestant versus Catholic), geographical (continents), and institutional (OECD versus non-OECD) clubs emerge endogenously and naturally as homogeneous classes on the basis of their economic structure. The dynamics both within and across the identified groups of countries are consistent with multiple equilibrium-growth models proposed by, for instance, Azariadis and Drazen (1990), therefore strengthening the viability of the convergence club hypothesis. In particular, higher stages of development are, on average, non linearly associated with higher stages of growth.
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    Journal of economic growth 4 (1999), S. 81-111 
    ISSN: 1573-7020
    Keywords: growth ; investment ; regimes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract The absence of continuous regime type measures that focus on institutions rather than outcomes besets studies on whether democratic or authoritarian regimes grow faster. Additional shortcomings include the failure to consider development stages and the erroneous endogenous specification of regimes. Given panel data on 105 countries from 1960 to 1989, the effective party/constitutional framework measure does not correlate with growth or investment in the total sample. But considering development levels, some evidence indicates that discretion decreases growth in advanced areas, and, contrary to theory, inhibits investment in poorer countries. Also, single-party dictatorships have higher investment ratios but do not grow faster than party-less regimes.
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    Journal of economic growth 4 (1999), S. 213-232 
    ISSN: 1573-7020
    Keywords: education ; work experience ; self-employment ; growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract We examine the implications for growth and development of the existence of two types of human capital: entrepreneurial and professional. Entrepreneurs accumulate human capital through a work-experience intensive process, whereas professionals’ human capital accumulation is education-intensive. Moreover, the return to entrepreneurship is uncertain. We show how skill-biased technological progress leads to changes in the composition of aggregate human capital; as technology improves, individuals devote less time to the accumulation of human capital through work experience and more to the accumulation of human capital through professional training. Thus, our model explains why entrepreneurs play a relatively more important role in intermediate-income countries and professionals are relatively more abundant in richer economies. It also shows that those countries that initially have too little of either entrepreneurial or professional human capital may end up in a development trap.
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    Journal of economic growth 4 (1999), S. 331-349 
    ISSN: 1573-7020
    Keywords: growth ; fertility ; income distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract This article analyzes the interaction between growth and fertility via income distribution in a model in which fertility decisions are motivated by old-age support. It provides an explanation of the demographic transition of an economy from a stage of increasing fertility and low growth to a stage of low fertility, high human capital investments, and high growth.
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    Review of industrial organization 14 (1999), S. 391-396 
    ISSN: 1573-7160
    Keywords: Fate ; growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract Fate bringeth economic growth and malfeasance giveth its gains
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  • 74
    ISSN: 1573-143X
    Keywords: apparent digestibility coefficient ; fish meal ; growth ; Nile tilapa (Oreochromis niloticus) ; plant proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Apparent digestibility coefficient (ADC) values for a number of ingredients of plant or animal origin were obtained in order to formulate diets based on such values and to evaluate growth performance of Nile tilapia Oreochromis niloticus fed four experimental diets in which fish meal was gradually replaced by a mixture of other ingredients. The digestibility of various diet components was measured by using an inert marker in the feed and by using the Guelph faeces collecting system. ADC values of the ingredients tested were generally high, especially for fish meal. It was found that extruded pea seed meal (92.6%), defatted soybean meal (94.4%), full-fat toasted soybean (90.0%) and micronized wheat (88.6%) were the best vegetable proteins tested. Lupin seed meal and faba bean meal had similar ADC values for protein and energy. Groups of tilapia, initial mean body weight (SD) 6.7 (0.1) g, were fed experimental diets with the same digestible protein (DP) and digestible energy (DE) containing graded levels of a mixture of vegetable ingredients as partial or total replacement of fish meal protein. A growth trial was conducted over 12 weeks as partial or total replacement of fish meal protein. A growth trial was conducted over 12 weeks at a water temperature of 25 °C. Significant differences were observed for weight gain among tilapia fed diets D0, D33, D66 and D100 (containing only animal protein, 33, 66, and 100% of plant protein, respectively). No significant differences were observed for voluntary intake among tilapia fed diets D0, D33 and D66. These values were significantly lower than those observed for tilapia fed plant protein based diet (D100) and suggest the possibility of partial replacement of fish meal by vegetable proteins without negative effects.
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    Aquaculture international 7 (1999), S. 357-360 
    ISSN: 1573-143X
    Keywords: feed intake ; growth ; silver trevally (Pseudocaranx dentex) ; temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 76
    ISSN: 1573-1561
    Keywords: European corn borer ; Ostrinia nubilalis (Hübner) ; growth ; development ; fecundity ; oviposition ; behavior ; eggs ; DIMBOA ; water extract ; plant extract ; maize ; Peruvian maize ; maize accessions ; host plant resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Twelve Peruvian maize, Zea mays, accessions were selected because of their relatively high level of field resistance to first-generation European corn borer (ECB), Ostrinia nubilalis, larval leaf-feeding. Water extracts of freeze-dried, powdered, leaf tissue were incorporated into a standard ECB diet, fed to larvae, and the effects on larval growth, development, and fecundity were measured. Larval and pupal weights were monitored as were the time elapsed in the larval, pupal, and adult stages. Adult fecundity and egg fertility were recorded. The experiment was a randomized block design (larvae and pupae) or a completely randomized design (adults) and analyzed with ANOVA (α = 0.05). Pairwise comparisons were made between groups of insects grown on diets containing extracts from the Peruvian lines, a standard diet, or diets containing extracts of a known susceptible inbred, and a known resistant inbred line. Survival was analyzed with a chi-squared test (α = 0.05). Two Peruvian accessions significantly reduced female larval and pupal weights, extended pupal and adult development time, and decreased survival of pupae and adults. Water extracts also had a pronounced impact on males; two accessions significantly reduced pupal weight and extended the time required to pupate, and one reduced male survival to adults. The results indicate that water-soluble factors from resistant Peruvian accessions inhibit the growth, developmental time, and survival of ECB. These resistance factors could be useful in the development of maize germplasm with insect-resistant traits.
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    Boundary layer meteorology 91 (1999), S. 495-504 
    ISSN: 1573-1472
    Keywords: Evaporation ; Heat storage ; Marsh ; Inversion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract Concurrent measurements of the surface energy balance components (net radiation, heat storage, and sensible and latent heat fluxes) were made in three communities (open water, Phragmites australis, Scirpus acutus) in a wetland in north-central Nebraska, U.S.A., during May-October, 1994. The Bowen ratio – energy balance method was used to calculate latent and sensible heat fluxes. This paper presents results from the open water area. The heat stored in water (G) was found to play a major role in the energy exchange over the water surface. During daytime, G consumed 45–60% of R n , the net radiation (seasonally averaged daytime G was about 127 W m−2). At night, G was a significant source of energy (seasonally averaged nighttime G was about -135 Wm−). The diurnal pattern of latent heat flux (λ E) did not follow that of R n . On some days, λ E was near zero during midday periods with large R n . The diurnal variability in λ E seemed to be significantly affected by temperature inversions formed over the cool water surface. The daily evaporation rate (E) ranged from 2 to 8 mm during the measurement period, and was generally between 70 and 135% of the equilibrium rate.
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  • 78
    ISSN: 1573-0603
    Keywords: Dichloromethylene diphosphate ; Hepatic stellate cell isolation ; Liposome ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Hepatic perisinusoidal cell population consists of hepatic stellate cells, Kupffer cells, endothelial cells, and Pit cells. These cells are isolated by enzymic digestion and purified by density gradient centrifugation. With isolation of stellate cells, conventional method is unable to eliminate the contamination of Kupffer cells because the densities of these two cells are similar. We report here an improved method for isolation of highly purified hepatic stellate cells, using dichloromethylene diphosphate (CL2MDP), which has selective cytotoxicity of Kupffer cells. Three days after the single intravenous administration of liposome-encapsulated CL2MDP, the Kupffer cells disappeared almost completely from the liver. Following Percoll density gradient centrifugation, the purity of the hepatic stellate cells exceeded 98% without any contamination of the Kupffer cells. Kupffer cells are reported to affect the physiological functions of stellate cells. The availability of highly purified stellate cells will facilitate the investigation of their functions in primary culture.
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    Biodegradation 10 (1999), S. 177-191 
    ISSN: 1572-9729
    Keywords: AQUASIM ; biodegradation ; biofilm ; growth ; kinetics ; methane ; modelling ; nitrification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract This article discusses the growth of methanotrophic biofilms. Several independent biofilm growths scenarios involving different inocula were examined. Biofilm growth, substrate removal and product formation were monitored throughout the experiments. Based on the oxygen consumption it was concluded that heterotrophs and nitrifiers co-existed with methanotrophs in the biofilm. Heterotrophic biomass grew on soluble polymers formed by the hydrolysis of dead biomass entrapped in the biofilm. Nitrifier populations developed because of the presence of ammonia in the mineral medium. Based on these experimental results, the computer program AQUASIM was used to develop a biological model involving methanotrophs, heterotrophs and nitrifiers. The modelling of six independent growth experiments showed that stoichiometric and kinetic parameters were within the same order of magnitude. Parameter estimation yielded an average maximum growth rate for methanotrophs, μm, of 1.5 ± 0.5 d−1, at 20 °C, a decay rate, bm, of 0.24 ± 0.1 d−1, a half saturation constant, $${\text{K}}_{{\text{S(CH}}_{\text{4}} {\text{)}}} $$ , of 0.06 ± 0.05 mg CH4/L, and a yield coefficient, $$Y_{CH_4 } $$ , of 0.57 ±: 0.04 g X/g CH4. In addition, a sensitivity analysis was performed on this model. It indicated that the most influential parameters were those related to the biofilm (i.e. density; solid-volume fraction; thickness). This suggests that in order to improve the model, further research regarding the biofilm structure and composition is needed.
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    GeoJournal 49 (1999), S. 279-288 
    ISSN: 1572-9893
    Keywords: globalisation ; growth ; information technology ; infrastructure ; knowledge ; modernisation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography
    Notes: Abstract This study examines the modernising role played by infrastructure and the transition of emphasis from physical infrastructure to knowledge-based infostructure as a source of economic growth in Singapore, noting the factors behind the change in strategy. Occupying a strategic sea route location and serving a resource-rich hinterland, Singapore inherited from the old British empire a well-established infrastructure when it achieved self-government in 1959. Since 1965, Singapore's development has been led by a pro-business developmentalist government, and strongly linked to technological advances in the West on which it also relies heavily for its exports and multinational corporation investments. From the 1980s, the government has launched a series of pro-IT plans to prepare the city-state's transition to an `intelligent island', and a regional hub for high-technology, and international financial transactions, a full-swing state-initiated strategy to leap from a semi-peripheral economy to be part of the developed core, and enhance its status to that of a world city. Despite barriers, some positive results have been observed. In terms of IT's spatial effect, it is largely overshadowed by the predeterministic long-term plans of the state's powerful planning authority.
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  • 81
    ISSN: 1573-5036
    Keywords: growth ; porewater ; salt marshes ; silicon ; Spartina ; tissue concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Analysis of silicon concentrations of various halophytes from salt marshes in the S.W. Netherlands shows that the silicon concentration of Spartina anglica (Gramineae) is relatively high. To study the influence of dissolved Si concentrations on growth and plant tissue concentrations of S. anglica, silicic acid was introduced into the sediment of natural patches of this halophyte occurring on a tidal flat. This resulted in a strong increase in dissolved silicon levels in the sediment porewater. In addition, S. anglica was cultured in the laboratory on nutrient solution enriched with dissolved silicon. Neither in the field nor in the laboratory experiment did the increased silicon levels have effects on shoot growth or led to consistent increases in the silicon concentration of plant tissues. Finally, different S. anglica stands in a number of salt marshes around the Oosterschelde basin were examined on sediment porewater silicon concentrations and silicon plant tissue concentrations. Sediment porewater silicon levels ranged between 36 and 554 μM. The average silicon concentration of the shoots from the various populations ranged between 3.52 and 11.73 mg/g DW. Consistent with the results of the field and laboratory experiments, there was no correlation between porewater silicon concentrations and average shoot length at the different sites, nor between porewater silicon concentrations and shoot silicon levels. Apparently, vegetative growth and tissue silicon concentrations of S. anglica do not respond to concentrations of dissolved Si in the range to which the plants were exposed naturally or experimentally in the field and in the laboratory (ca. 15–550 μM). In the data set pertaining to the different S. anglica field populations, however, negative correlations were observed between the average number of leaves per shoot at the different locations and the total silicon content of the 4th and 2nd leaves and of the entire shoots. The possible mechanisms explaining differences in tissue Si concentrations are discussed.
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  • 82
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    Hydrobiologia 398-399 (1999), S. 91-100 
    ISSN: 1573-5117
    Keywords: Polysiphonia setacea ; Rhodophyta ; culture ; growth ; biogeography ; Mediterranean Sea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The red alga Polysiphonia setacea Hollenberg (=Womersleyella setacea (Hollenberg) R. Norris), described originally from the Hawaiian Islands and later reported for other tropical localities, has recently become widespread in the Mediterranean. In several localities it forms a dense, almost monospecific turf but, despite its abundance, it appears to reproduce only vegetatively; neither sporangia nor sexual reproductive structures have thus far been found. In order to elucidate its life history, plants were cultured in a variety of conditions of temperature, daylength and photon irradiance, and the upper thermal limit was also determined. Isolates of P. setacea grew well in culture, but were more tufted and branched than wild plants. No reproduction by spores or gametes was observed and only an unusual form of vegetative regeneration was found. Some pericentral cells became darker and larger than the others and produced proliferations from which new plants arose. Plants grew best at 15 and 20 °C, and relatively poor growth was observed at 10 and 25 °C. At 20 °C growth was better in long days than in short days. The upper thermal limit was 28 °C, and plants were able to tolerate a temperature as low as 5 °C for 4 weeks without any damage. These observations show that P. setacea is well adapted to the environmental conditions of the western Mediterranean, and there is good agreement with the phenology of the species in the wild. Although this entity has been treated as an introduction from a tropical area, our results suggest that the Mediterranean entity would not be able to survive or grow in surface waters of tropical areas whence this species has been reported. However, the occurrence of thermal ecotypes in P. setacea is a possibility and further studies, based perhaps on molecular data, are necessary to assess the origin of the Mediterranean populations.
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  • 83
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    Cellular and molecular neurobiology 19 (1999), S. 309-323 
    ISSN: 1573-6830
    Keywords: cytochrome P450 ; enzyme inhibition ; enzyme induction ; pharmacokinetics ; drug interaction ; in vitro assessment ; clinical assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. The cytochrome P450 enzyme family is one of the major drug metabolizing systems in man. 2. Factors such as age, gender, race, environment, and drug treatment may have considerable influence on the activity of these enzymes. 3. There are now well-established in vitro techniques for assessing the role of specific cytochrome P450 enzymes in the metabolism of drugs, as well as the inhibitory or inducing effects of drugs on enzyme activity. In vitro data have been utilized to predict clinical outcomes (i.e., pharmacokinetic interactions), with close correlations between in vitro and in vivo data. 4. This information can be of considerable practical assistance to clinicians, to help with rational prescribing or to prevent or minimize the potential for drug interactions.
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  • 84
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    Cellular and molecular neurobiology 19 (1999), S. 355-372 
    ISSN: 1573-6830
    Keywords: enantiomers ; racemic ; chiral ; stereoselective ; pharmacokinetics ; cytochrome P450 ; geometric isomers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. Many drugs used to treat psychiatric disorders contain a chiral center or a center of unsaturation and are marketed as a mixture of the resultant enantiomers or geometric isomers, respectively. These enantiomers or geometric isomers may differ markedly with regard to their pharmacodynamic and/or pharmacokinetic properties. 2. Examples of the effects of chiral centers or geometric centers on such properties are given for drugs from the following classes: antidepressants (tricyclics, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, viloxazine, bupropion, trazodone, mianserin, venlaflaxine); benzodiazepines, zoplicone, and antipsychotics. 3. As described in this review, there are several notable examples of psychiatric drugs currently available where the individual enantiomers or geometric isomers differ considerably with regard to factors such as effects on amine transport systems, interactions with receptors and metabolizing enzymes, and clearance rates from the body. Indeed, relatively recent developments in analytical and preparative resolution of racemic and geometric drug mixtures and increased interest in developing new drugs which interact with specific targets, which have been described in detail at the molecular level, have resulted in increased emphasis on stereochemistry in drug development.
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  • 85
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    Cellular and molecular neurobiology 19 (1999), S. 443-466 
    ISSN: 1573-6830
    Keywords: selective serotonin reuptake inhibitors ; metabolism ; pharmacokinetics ; fluoxetine ; fluvoxamine ; paroxetine ; sertraline ; citalopram ; cytochrome P450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. Five drugs with the predominant pharmacologic effect of inhibiting the neuronal reuptake of serotonin are available worldwide for clinical use. This class of psychoactive drugs, known as selective serotonin reuptake inhibitors (SSRIs), is comprised of fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram. 2. The SSRIs appear to share similar pharmacodynamic properties which translate to efficacy in the treatment of depression and anxiety syndromes. The drugs are differentiated by their pharmacokinetic properties with regard to stereochemistry, metabolism, inhibition of cytochrome enzymes, and participation in drug–drug interactions. Studies focusing on the relationship of plasma drug concentration to therapeutic and adverse effects have not confirmed the value of plasma concentration monitoring. 3. This review summarizes the metabolism and relevant pharmacokinetic properties of the SSRIs.
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  • 86
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    Hydrobiologia 398-399 (1999), S. 291-297 
    ISSN: 1573-5117
    Keywords: Porphyra ; conchocelis ; aquaculture ; growth ; Alaska ; nori
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Experiments were performed to determine the range and optima of environmental conditions under which indigenous species of Alaskan Porphyra can grow. Growth of the conchocelis phase of Porphyra abbottae, P. torta and P. pseudolinearis was measured, when cultured in enriched media, under long days (16 h light) and varying conditions of irradiance (20, 40, 80 and 160 μmol photons m−2 s−1), temperature (7, 11, 15 and 19 °C) and salinity (5, 10, 20, 30 and 40‰). Optimal growth (7.6% increase in volume day−1) of P. abbottae occurred at 11 °C, 80 μmol photons m−2 s−1 and 30‰. Porphyra torta grew best (6.5% day−1) at 15 °C, 80 μmol photons m−2 s−1 and 30‰. Porphyra pseudolinearis generally had higher growth rates than the other two species with optimal growth (8.8% day−1) occurring at 7 °C, 160 μmol photons m−2 s−1 and 30‰. For all three species salinity between 20 and 40‰ had little effect on growth, but there was virtually no growth at salinity of 10‰ and below. Irradiances between 20 and 160 μmol photons m−2 s−1 generally had little effect on growth rates. However, growth of P. abbottae increased with irradiance at 7 °C but was inhibited at irradiances over 40 μmol photons m−2 s−1 at 15 °C and higher. Porphyra torta also showed growth inhibition at 15 °C and higher irradiances. Porphyra pseudolinearis appeared to be the most robust species with respect to tolerance to extremes of salinity and irradiance.
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  • 87
    ISSN: 1573-5117
    Keywords: seaweed ; morphology ; seasonal variation ; growth ; phenotypic modulation ; kelp ; Undaria pinnatifida
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Undaria pinnatifida (Harvey) Suringar is currently divided into two morphological forms, f. typica Yendo. and f. distans Miyabe & Okamura. The objective of this study was to determine the effects of seasonal variation in growth rate on the morphology of U. pinnatifida, and to define the form of U. pinnatifida growing in Otago Harbour, New Zealand. Morphological variables (stipe length, blade length, blade width, sporophyll length and degree of blade incision), growth rates (frond, blade and stipe) and blade erosion were measured each month from August 1993 to February 1995, and compared using correspondence analysis. Variation in the morphology of U. pinnatifida was largely accounted for by varying growth rates. Definition of the form of U. pinnatifida growing in Otago Harbour is equivocal because morphological characteristics of both f. typica and f. distans were exhibited at different times of the year.
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  • 88
    ISSN: 1573-5117
    Keywords: Gracilaria ; growth ; irradiance ; plant growth regulators ; salinity ; temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Growth and tolerance of Gracilaria vermiculophylla (Ohmi) Papenfuss from Shikoku Island were investigated under a variation of temperature (5–30 °C), salinity (5–60‰), and photon irradiance (20–100 μmol photons m−2 s−1) in unialgal culture. G. vermiculophylla showed wide tolerances for all factors tested, characterizing a euryhaline and eurythermal species. Two clones, one of a tetrasporophyte and the other of a female gametophyte, showed different growth rates, attributable to the difference either in phase or in genotype. The optimum temperature for the growth of the tetrasporophyte clone was 15–25 °C while that of the gametophyte clone was 20–30 °C. Maximum growth of both phases was observed at 80–100 μmol m−2 s−1. G. vermiculophylla presented higher growth rates in low salinities (15–30‰). Tissue cultures were established in solid ASP 12-NTA medi um supplemented with plant growth regulators (PGR), 0.5% agar, 1.0% sucrose and 0.5% inositol. Effects of two auxins (indole-3-acetic acid (IAA), and 2,4-dichlorophenoxyacetic acid (2,4-D)), and one cytokinin (6-benzylaminopurine (BA)) were tested in concentrations ranging from 0.1 to 10.0 mg l−1. Growth of apical segments was significantly stimulated by the majority of treatments supplemented with PGR, while maximum growth of calluses was observed in treatments with low concentration of auxins or BA (1.0 mg l−1). All treatments supplemented with PGR significantly promoted the growth of intercalary segments, except for IAA (1.0 mg l−1) in combination with BA (1.0 mg l−1). Growth of calluses originating from intercalary segments was observed in treatments with IAA (0.1 mg l−1), 2,4-D (10.0 mg l−1) or IAA (1.0 mg l−1) in combination with BA (0.1 mg l−1). Tr eatments with high concentration of IAA and BA (10.0 mg l−1) were lethal for apical and intercalary segments. These results show that auxin and cytokinin play a regulatory role on the growth of G. vermiculophylla in tissue culture. Furthermore, results on the effects of temperature, salinity and irradiance indicate that G. vermiculophylla could be cultivated in brackish temperate environments with potential for economic purposes and for pollution management.
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  • 89
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    Cellular and molecular neurobiology 19 (1999), S. 373-409 
    ISSN: 1573-6830
    Keywords: antidepressants ; tricyclic ; metabolism ; hydroxy metabolites ; pharmacokinetics ; pharmacogenetics ; drug–drug interactions ; toxicity ; plasma concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. Despite the considerable advances in the treatments available for mood disorders over the past generation, tricyclic antidepressants (TCAs) remain an important option for the pharmacotherapy of depression. 2. The pharmacokinetics of TCAs are characterized by substantial presystemic first-pass metabolism, a large volume of distribution, extensive protein binding, and an elimination half-life averaging about 1 day (up to 3 days for protriptyline). 3. Clearance of tricyclics is dependent primarily on hepatic cytochrome P450 (CYP) oxidative enzymes. Although the activities of some P450 isoenzymes are largely under genetic control, they may be influenced by external factors, such as the concomitant use of other medications or substances. Patient variables, such as ethnicity and age, also affect TCA metabolism. The impact of gender and related reproductive issues is coming under increased scrutiny. 4. Metabolism of TCAs, especially their hydroxylation, results in the formation of active metabolites, which contribute to both the therapeutic and the adverse effects of these compounds. 5. Renal clearance of the polar metabolites of TCAs is reduced by normal aging, accounting for much of the increased risk of toxicity in older patients. 6. Knowledge of factors affecting the metabolism of TCAs can further the development and understanding of newer antidepressant medications.
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  • 90
    ISSN: 1573-2932
    Keywords: Ponderosa pine ; elevated CO2 ; growth ; gene expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Biochemical and gene expression changes in response to elevated atmospheric CO2 were investigated in five maternal half-sibling breeding families of Ponderosa pine. Seedlings were grown in a common garden located at Lawrence Livermore National Laboratory, in open-topped chambers (OTC) for two years. Chamber atmospheres were maintained at ambient, ambient + 175 μL L-1, CO2, or ambient + 350 μL L-1CO2. Growth measurements showed significant increases in stem volumes and volume enhancement ratios in three of the five families studied when grown under elevated CO2. Biochemical and gene expression studies were undertaken to gain a mechanistic understanding of these phenotypic responses. Biochemical studies focused on sucrose phosphate synthase (SPS) specific activities at increase CO2 levels. Kinetic evaluations of SPS showed an increase in VMax. Specific SPS probes revealed increases in the transcriptional levels of one SPS gene with exposure to increasing CO2. RT-PCR differential gene displays showed that overall only a small fraction of visualized gene transcripts responded to elevated CO2 (8-10%). There were also significant differences between the gene expression patterns of the different families, some of which correlated with alterations in growth at elevated CO2 levels.
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  • 91
    ISSN: 1573-904X
    Keywords: antisense ; Brown-Norway rat ; oligodeoxynucleotide ; pulmonary delivery ; ISIS 2105 ; pharmacokinetics ; airway inflammation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate the pulmonary distribution of CGP69846A (ISIS 5132), a phosphorothioate oligonucleotide, following intra-tracheal (i.t.) instillation into Brown-Norway rats. Methods. The pharmacokinetic profile of [3H]-CGP69846A was investigated following i.t. instillation into both naïve and inflamed airways of Brown-Norway rats. The cellular distribution was determined using autoradiography, immunohistochemistry and flow cytometry/fluorescence microscopy, in inflamed airways. Results. CGP69846A displayed a dose-dependent lung retention following i.t. administration which was unaffected by local inflammation. Autoradiography and immunohistochemistry showed distribution to alveolar macrophages, eosinophils, bronchial and tracheal epithelium and alveolar cells. Studies with [FITCJ-CGP69846A demonstrated a preferential association of oligonucleotide with leukocytes in bronchial lavage fluid of: macrophages 〉 eosinophils = neutrophils 〉 〉 lymphocytes. Conclusions. The dose-dependency of lung retention together with cell-specific uptake suggests that the lung can be used as a local target for antisense molecules with potentially minimal systemic effects. Furthermore, the preferential targeting of macrophages and the airway epithelium by oligonucleotides may represent rational cellular targets for antisense therapeutics.
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  • 92
    ISSN: 1573-904X
    Keywords: nonlinear mixed effects modeling (NONMEM) ; pharmacokinetics ; telmisartan ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 93
    ISSN: 1573-904X
    Keywords: antisense phosphorothioate oligonucleotide ; stealth liposome ; pharmacokinetics ; monkey ; capillary gel electrophoresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study examined the pharmacokinetics and tissue distribution of an antisense oligonucleotide ISIS 2503, formulated in stealth (pegylated) liposomes (encapsulated) or in phosphate-buffered saline (unencapsulated). Methods. Encapsulated or unencapsulated ISIS 2503 was administered to rhesus monkeys by intravenous infusion. The concentrations of ISIS 2503 and metabolites in blood, plasma, and tissue samples were determined by capillary gel electrophoresis. Results. Plasma concentrations of encapsulated ISIS 2503 decreased mono-exponentially after infusion with a mean half-life of 57.8 hours. In contrast, the concentration of unencapsulated ISIS 2503 in plasma decreased rapidly with a mean half-life of 1.07 hours. Both encapsulated and unencapsulated ISIS 2503 distributed widely into tissues. Encapsulated ISIS 2503 distributed primarily to the reticulo-endothelial system and there were few metabolites observed. In contrast, unencapsulated ISIS 2503 distributed rapidly to tissue with highest concentration seen in kidney and liver. Nuclease-mediated metabolism was extensive for unencapsulated oligonucleotide in plasma and tissues. Conclusions. The data suggest that stealth liposomes protect ISIS 2503 from nucleases in blood and tissues, slow tissue uptake, and slow the rate of clearance from the systemic circulation. These attributes may make these formulations attractive for delivering oligonucleotides to sites with increased vasculature permeability such as tumors or sites of inflammation.
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  • 94
    ISSN: 1573-904X
    Keywords: aminolevulinic acid ; intravesical ; pharmacokinetics ; photodiagnosis ; bladder ; cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To examine the stability and systemic absorption of aminolevulinic acid (ALA) in dogs during intravesical administration. Methods. Nine dogs received an intravesical dose of ALA either with no prior treatment, after receiving ammonium chloride for urinary acidification, or after receiving sodium bicarbonate for urinary alkalinization. Urine and blood samples collected during and after administration were monitored for ALA using an HPLC assay developed in our laboratories. Concentrations of pyrazine 2,5-dipropionic acid, the major ALA degradation product, and radiolabeled inulin, a nonabsorbable marker for urine volume, were also determined. Results. Less than 0.6% of intravesical ALA doses was absorbed into plasma. Urine concentrations decreased to 37% of the initial concentration during the 2 hour instillation. Decreases in urinary ALA and radiolabeled inulin concentrations were significantly correlated, indicating that urine dilution accounted for over 80% of observed decreases in urinary ALA. ALA conversion to pyrazine 2,5-dipropionic acid was negligible. Conclusions. These studies demonstrate that ALA is stable and poorly absorbed into the systemic circulation during intravesical instillation. Future studies utilizing intravesical ALA for photodiagnosis of bladder cancer should include measures to restrict fluid intake as a means to limit dilution and maximize ALA concentrations during instillation.
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  • 95
    ISSN: 1573-904X
    Keywords: diffusion model ; drug delivery system ; ocular penetration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the ocular pharmacokinetics of beta-blockers (timolol and tilisolol) after instillation in the albino rabbit using a mathematical model that includes a diffusion process. Methods. The disposition of fluorescein isothiocyanate-dextran (FITC-dextran, molecular weight 4400), timolol, and tilisolol was determined in tear fluid and aqueous humor after instillation or ocular injection in rabbits. The in vivo penetration parameters were estimated by fitting the concentration-time profiles to the Laplace equations based on a diffusion model using MULTI(FILT) program. Thein vivo permeability of drugs was measured across cornea using a two-chamber diffusion cell. Results. Concentration-time profiles of drugs in the tear fluid after instillation showed a monoexponential curve. Although a monoexponential curve was observed in the aqueous humor concentration of FITC-dextran after injection into the aqueous chamber, timolol and tilisolol showed a biexponential curve. On the basis of these results, anin vivo pharmacokinetic model was developed for estimation of penetration parameters. The in vitro partition parameters were higher than those of the in vivo parameters. Conclusions. The ocular absorption of timolol and tilisolol was characterized using an in vivo pharmacokinetic model and in vivo penetration parameters.
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  • 96
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    Pharmaceutical research 16 (1999), S. 1608-1615 
    ISSN: 1573-904X
    Keywords: tenidap ; pharmacokinetics ; EM algorithm ; nonlinear mixed-effects modelling ; covariates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a pharmacokinetic model for tenidap and to identify important relationships between the pharmacokinetic parameters and available covariates. Methods. Plasma concentration data from several phase I and phase II studies were used to develop a pharmacokinetic model for tenidap, a novel anti-rheumatic drug. An appropriate pharmacokinetic model was selected on the basis of individual nonlinear regression analyses and an EM algorithm was used to perform a nonlinear mixed-effects analysis. Scatter plots of posterior individual pharmacokinetic parameters were used to identify possible covariate effects. Results. Predicted responses were in good agreement with the observed data. A bi-exponential model with zero order absorption was subsequently used to develop the mixed-effects model. Covariate relationships selected on the basis of differences in the objective function, although statistically significant, were not particularly strong. Conclusions. The pharmacokinetics of tenidap can be described by a bi-exponential model with zero order absorption. Based on differences in the log-likelihood, significant covariate-parameter relationships were identified between smoking and CL, and between gender and Vss and CLd. Simulated sparse data analyses indicated that the model would be robust for the analysis of sparse data generated in observational studies.
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  • 97
    ISSN: 1573-904X
    Keywords: amphotericin B ; liposomes ; pharmacokinetics ; tissue distribution ; toxicity ; toxicokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Amphotericin B (AmB) in small, unilamellar liposomes (AmBisome ®) has an improved therapeutic index, and altered pharmacokinetics. The repeat-dose safety and toxicokinetic profiles of AmBisome were studied at clinically relevant doses. Methods. Beagle dogs (5/sex/group) received intravenous AmBisome (0.25, 1,4, 8, and 16 mg/kg/day), empty liposomes or vehicle for 30 days. AmB was determined in plasma on days 1, 14, and 30, and in tissues on day 31. Safety parameters included body weight, clinical chemistry, hematology and microscopic pathology. Results. Seventeen of twenty animals receiving 8 and 16 mg/kg were sacrificed early due to weight loss caused by reduced food intake. Dose-dependent renal tubular nephrosis, and other effects characteristic of conventional AmB occurred at 1 mg/kg/day or higher. Although empty liposomes and AmBisome increased plasma cholesterol, no toxicities unique to AmBisome were revealed. Plasma ultrafiltrates contained no AmB. AmBisome achieved plasma levels 100-fold higher than other AmB formulations. AmBisome kinetics were non-linear, with clearance and distribution volumes decreasing with increasing dose. This, and nonlinear tissue uptake, suggest AmBisome disposition was saturable. Conclusions. AmBisome has the same toxic effects as conventional AmB, but they appear at much higher plasma exposures. AmBisome's non-linear pharmacokinetics are not associated with increased risk, as toxicity increases linearly with dosage. Dogs tolerated AmBisome with minimal to moderate changes in renal function at doses (4 mg/kg/day) producing peak plasma concentrations of 18−94 µg/mL.
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    Pharmaceutical research 16 (1999), S. 176-185 
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; pharmacodynamics ; pharmacology ; modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Pharmacokinetic/pharmacodynamic (PK/PD)-modeling links dose-concentration relationships (PK) and concentration-effect relationships (PD), thereby facilitating the description and prediction of the time course of drug effects resulting from a certain dosing regimen. PK/PD-modeling approaches can basically be distinguished by four major attributes. The first characterizes the link between measured drug concentration and the response system, direct link versus indirect link. The second considers how the response system relates effect site concentration to the observed outcome, direct versus indirect response. The third regards what clinically or experimentally assessed information is used to establish the link between concentration and effect, hard link versus soft link. And the fourth considers the time dependency of pharmacodynamic model parameters, distinguishing between time-variant versus time-invariant. Application of PK/PD-modeling concepts has been identified as potentially beneficial in all phases of preclinical and clinical drug development. Although today predominantly limited to research, broader application of PK/PD-concepts in clinical therapy will provide a more rational basis for patient-specific dosage individualization and may thus guide applied pharmacotherapy to a higher level of performance.
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  • 99
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    Pharmaceutical research 16 (1999), S. 261-265 
    ISSN: 1573-904X
    Keywords: crystal habit ; trimethoprim suspension ; physical stability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The role of crystal habit in influencing the physical stability and pharmacokinetics of trimethoprim suspensions was examined. Methods. Different habits of trimethoprim (TMP) were obtained by recrystallizing the commercial sample (PD) utilizing solvent-change precipitation method. Four distinct habits (microscopic observation) belonging to the same polymorphic state (DSC studies) were selected for studies. Preformulation and formulation studies were carried out on suspension dosage forms containing these crystals. The freshly prepared suspensions were also evaluated for their pharmacokinetic behaviour on healthy human volunteers using a cross over study. Results. Variation of crystallization conditions produces different habits of TMP. Among the different crystal habits exhibiting same polymorphic state, the most anisometric crystal showed best physical stability in terms of sedimentation volume and redispersibility. However, habit did not significantly affect the extent of TMP excreted in urine. Conclusions. Modification of surface morphology without significantly altering the polymorphic state can be utilized for improving physical stability of TMP suspensions. However, the pharmacokinetic profile remains unaltered.
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  • 100
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    Pharmaceutical research 16 (1999), S. 309-313 
    ISSN: 1573-904X
    Keywords: hyperlipidemia ; hypercholesterolemia ; nifedipine ; pharmacokinetics ; protein binding ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The effect of hyperlipidemia on nifedipine pharmacokinetics was studied. The mechanisms by which hyperlipidemia affects pharmacokinetics of drugs are mainly undetermined. Hyperlipidemia may decrease the fraction of unbound drug in plasma and/or decrease intrinsic ability of the cytochrome P-450 systems due to excess membrane cholesterol. Hyperlipidemia is a primary risk factor for coronary artery disease leading to hypertension and ischemic heart disease, for which nifedipine, a calcium channel blocker, is used. Methods. Poloxamer 407 (P407)-induced hyperlipidemic rat model was used to study the effects of hyperlipidemia on the pharmacokinetics of nifedipine (6 mg kg−1 given iv, ip and po). Total plasma cholesterol levels increased from 0.82−2.02 to 5.27−11.05 mmol L−1 48 h post P407 administration (Ig kg−1, ip). Protein binding studies were conducted by an ultrafiltration method. Results. Hyperlipidemia significantly decreased CLTB by 38% and CLTB/F by 45 and 42% following po and ip doses, respectively, thereby increasing AUC0−∞, Cmax and half-life. Absolute bioavailability and Vdss remained unchanged. AUC0−∞ was affected to the same extent in each route of administration, therefore, the effect was mainly systemic rather than presystemic. Hyperlipidemia significantly lowered the fraction unbound in plasma by approximately 31%. Conclusions. The altered pharmacokinetics of nifedipine by P407-induced HYPERLIPIDEMIA may be, at least in part, due to the decrease in fraction unbound in plasma. A decrease in intrinsic clearance, however, cannot be ruled out.
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