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  • 1
    Electronic Resource
    Electronic Resource
    Human Interindividual Variability in Parameters Related to Health Risks (1999)
    Springer
    Risk analysis 19 (1999), S. 711-726 
    Details
    ISSN: 1539-6924
    Keywords: variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure-related parameters and parameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non-cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: •Contact Rate (Breathing rates per body weight; fish consumption per body weight) •Uptake or Absorption as a Fraction of Intake or Contact Rate •General Systemic Availability Net of First Pass Elimination and Dilution via Distribution Volume (e.g., initial blood concentration per mg/kg of uptake) •Systemic Elimination (half life or clearance) •Active Site Concentration per Systemic Blood or Plasma Concentration •Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) •Functional Reserve Capacity–Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process–differences among people in “functional reserve capacity.” This has the implication that relevant information for estimating effective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants that are thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007045922532
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  • 2
    Electronic Resource
    Electronic Resource
    (±)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 579-585 
    Details
    ISSN: 1432-1912
    Keywords: ALEPH-2 Serotonin receptor binding ; Anxiolytics ; Serotonin syndrome ; Phenylisopropylamines ; Rat ; Hypothermia ; Psychedelics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serotonergic behavioral responses, effects on motor activity and core temperature, and binding properties of the novel putative anxiolytic amphetamine derivative (±)1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), were examined in rodents in order to elucidate the mechanism underlying its anxiolytic-like effect. After peripheral administration in rats, ALEPH-2 induced some symptoms of the serotonergic syndrome, e.g. forepaw treading and flat body posture. Additionally, a decrease in motor activity was observed. No significant effects on the number of head shakes were observed after injection, although high inter-subject variability was noted. Higher doses of ALEPH-2, in the range exhibiting anxiolytic properties (4mg/kg), elicited significant hypothermia in mice. The affinity of the drug for 5-HT2A/2C receptors ([3H]ketanserin sites) was in the nanomolar range (Ki = 173 nM), whereas for 5-HT1A, benzodiazepine sites, and GABAA receptors, the affinity was micromolar or lower. Based on these results the mechanism of action and the anxiolytic-like properties of ALEPH-2 are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00170831
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  • 3
    Electronic Resource
    Electronic Resource
    (±)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2) a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 579-585 
    Details
    ISSN: 1432-1912
    Keywords: Key words ALEPH-2 ; Serotonin receptor binding ; Anxiolytics ; Serotonin syndrome ; Phenylisopropylamines ; Rat ; Hypothermia ; Psychedelics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serotonergic behavioral responses, effects on motor activity and core temperature, and binding properties of the novel putative anxiolytic amphetamine derivative (±)1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), were examined in rodents in order to elucidate the mechanism underlying its anxiolytic-like effect. After peripheral administration in rats, ALEPH-2 induced some symptoms of the serotonergic syndrome, e.g. forepaw treading and flat body posture. Additionally, a decrease in motor activity was observed. No significant effects on the number of head shakes were observed after injection, although high inter-subject variability was noted. Higher doses of ALEPH-2, in the range exhibiting anxiolytic properties (4mg/kg), elicited significant hypothermia in mice. The affinity of the drug for 5-HT2A/2C receptors ([3H]ketanserin sites) was in the nanomolar range (Ki=173 nM), whereas for 5-HT1A, benzodiazepine sites, and GABAA receptors, the affinity was micromolar or lower. Based on these results the mechanism of action and the anxiolytic-like properties of ALEPH-2 are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00170831
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of nicotine on the acoustic startle reflex amplitude in rats (1991)
    Springer
    Psychopharmacology 104 (1991), S. 244-248 
    Details
    ISSN: 1432-2072
    Keywords: Nicotine ; Startle ; Reflex ; Sensorimotor reactivity ; Rat ; Attention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The acoustic startle reflex was used to measure changes in sensorimotor reactivity in response to nicotine administration and cessation. Male rats received saline, 6 mg/kg/day or 12 mg/kg/day nicotine delivered subcutaneously by osmotic minipumps. The pumps delivered their contents during a 10-day period of implantation, after which time they were explanted. Animals were tested for startle reflex amplitudes using two levels of white noise bursts prior to pump implantation, on days 1 and 7 of nicotine or saline administration, and on several days following drug cessation. Nicotine produced a dose-dependent increase in startle amplitude during the period of administration that decreased during cessation. Results are interpreted in terms of nicotine's actions to enhance attentional processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244186
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  • 5
    Electronic Resource
    Electronic Resource
    The tanycyte of the rat median eminence (1979)
    Springer
    Cell & tissue research 200 (1979), S. 329-334 
    Details
    ISSN: 1432-0878
    Keywords: Median eminence ; Axon terminals ; Tanycytes ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The present ultrastructural study proves the existence of nerve terminals closely apposed to the plasmalemmata of tanycytes in the rat median eminence. Several of these “axo-tanycytic” endings display remarkable accumulations of agranular endoplasmic reticulum in the form of pleomorphic vesicles which are closely apposed on either side of the plasma membrane of each cell compartment. Some of these vesicular profiles give the impression of structural continuity across both membrane systems. This phenomenon is discussed in the context of being a potential substratum for communication between both cell compartments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00236425
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  • 6
    Electronic Resource
    Electronic Resource
    In vitro analysis of the cellular localization of luteinizing hormone releasing factor (LRF) in the basal hypothalamus of the rat (1974)
    Springer
    Cell & tissue research 149 (1974), S. 371-378 
    Details
    ISSN: 1432-0878
    Keywords: LRF ; Hypothalamic localization ; Rat ; Ependyma ; Glia ; Light and electron microscopic Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Light and electron microscopic autoradiographic analysis of the medial basal hypothalamus of rat brains incubated for 30 and 60 minutes in tritiated luteinizing releasing factor (3H-LRF) revealed selective uptake in the form of silver grains over specialized ependyma (tanycytes) and perivascular glial cells in the palisade-contact zone of the median eminence. The functional capacity of tanycytes and glia are discussed in light of these data.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00226771
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  • 7
    Electronic Resource
    Electronic Resource
    Ultrastructural changes in the median eminence of the rat following deafferentation of the basal hypothalamus (1970)
    Springer
    Cell & tissue research 105 (1970), S. 1-32 
    Details
    ISSN: 1432-0878
    Keywords: Median eminence ; Rat ; Deafferentation ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary This report concerns a light and electron microscopic investigation of the median eminence and dorsal infundibular stem of the rat following surgical isolation (deafferentation). Using a modification of the Halász technique, the basal hypothalamus, including the arcuate nucleus and median eminence were surgically isolated from surrounding structures. Special attention was directed to the contact (external) zone of the median eminence and rostral infundibulum where tuberohypophyseal axons as well as ependymal cell processes abut upon the abluminal basement membrane of the portal perivascular space. The results of this study to date suggest that 9, 20, and 40 days following surgical isolation, there is a distinct increase in the population of tuberohypophyseal dense core vesicles. It is suggested that deafferentation abolishes inhibitory and excitatory input that serves to modify the cellular dynamics of tuberohypophyseal neurosecretory elements. Comments are also made on the presence of cistern-like structures in the lateral median eminence; the presence of vesicle-like inclusions in terminal ependymal processes is discussed in relationship to the role that ependyma may play in linking the third ventricle with the adenohypophysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00340562
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  • 8
    Electronic Resource
    Electronic Resource
    Phenobarbital Disposition in Adult and Neonatal Rabbits (1994)
    Springer
    Pharmaceutical research 11 (1994), S. 1204-1206 
    Details
    ISSN: 1573-904X
    Keywords: phenobarbital ; pharmacokinetics ; milk ; rabbit ; neonate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018957420197
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  • 9
    Electronic Resource
    Electronic Resource
    Attenuation of furosemide's diuretic effect by indomethacin: Pharmacokinetic evaluation (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 265-274 
    Details
    ISSN: 1573-8744
    Keywords: furosemide ; indomethacin ; prostaglandin ; pharmacokinetics ; pharma-codynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and pharmacodynamics of intravenous furosemide, 40 mg, were studied in four normal males in a crossover fashion with and without indomethacin pretreatment. In each study 16 plasma and 10 urine samples were collected over 24 hr. Fluid and electrolyte urinary losses were replaced orally throughout the study. Unchanged furosemide and indomethacin were measured using HPLC; urinary sodium was measured by flame photometry. Pretreatment with indomethacin resulted in increased and prolonged furosemide plasma levels, increased area under the curve, decreased plasma clearance, decreased renal clearance, increased half-life, no change in volume of distribution, and decreased sodium excretion and urine volume. Analysis of sodium excretion rate with time shows that the inhibiting effect of indomethacin was greater during the first 2 hr than at later times.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01060017
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  • 10
    Electronic Resource
    Electronic Resource
    Determinants of bumetanide response in the dog: Effect of probenecid (1983)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 31-46 
    Details
    ISSN: 1573-8744
    Keywords: bumetanide ; probenedd ; pharmacokinetics ; pharmacodynamics ; doseresponse relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and pharmacodynamics of intravenous bumetanide (0.250 mg/kg), alone (treatment I) and after probenecid pretreatment (treatment II), were studied in four mongrel dogs. Lactated Ringer's solution was administered by vein throughout both treatments at a flow rate of 2 ml/min to avoid fluid and electrolyte depletion. Bumetanide and probenecid concentrations were analyzed by HPLC, sodium by flame photometry, and creatinine by colorimetry. Although the probenecid markedly reduced the plasma and renal clearances of bumetanide, as well as the fraction excreted unchanged in the urine, there was no significant difference between treatments I and II in the 4-hr natriuretic and diuretic responses. However, analysis of the dose-response curves between treatments I and II showed that sodium, excretion was better correlated with bumetanide urinary excretion rate than with plasma concentration. The reasons for a poor correlation between treatments during the early time periods are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061766
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