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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1995), S. 28-35 
    ISSN: 1432-1912
    Keywords: 5-HT4 receptors ; 5-Hydroxytryptamine ; SB 203186 ; Porcine sinoatrial tachycardia ; Porcine and human atria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the blockade of the positive inotropic effects of 5-hydroxytryptamine (5-HT) by SB 203 186 (piperidinoethyl-indole-3-carboxylate hydrochloride) and its affinity for 5-HT4 receptors of human right atrium and piglet left atrium. We also compared the blocking effects of SB 203 186 against 5-HT-evoked tachycardia in anaesthetised adult Yucatan minipigs as well as new-born Camborough piglets. SB 203 186 caused competitive antagonism of the positive inotropic effects of 5-HT in electrically paced atrial preparations of man (pK B = 8.9) and piglet (pK B = 8.5) at concentrations (up to 0.3 μmo]/l) which were devoid of depressant or stimulant effects. The affinity of SB 203 186 for atrial 5-HT4 receptors was 30–160 times higher than that of tropisetron. 5-HT caused tachycardia with similar potency and efficacy in Yucatan minipigs and new-born Camborough piglets. SB 203 186 (0.1–3 mg/kg, i.v.) surmountably antagonised 5-HT-evoked tachycardia in anaesthetised Yucatan minipigs or new-born Camborough piglets with similar potency. The blocking potency of SB 203 186 in Yucatan minipigs was 17 times higher than that of tropisetron. Intraduodenally administered SB 203 186 (0.3–3 mg/kg) to new-born Camborough piglets produced blockade of 5-HT-evoked tachycardia which was maximal after 20 min and lasted for more than 3 h with 0.3 mg/kg. The antagonism produced by the SB 203 186 administration in new-born Camborough piglets was dose-related and threefold greater through the intravenous route than through the intraduodenal route. We conclude that SB 203 186 is an antagonist with nanomolar affinity for both human and porcine atrial 5-HT4 receptor. The in vivo results demonstrate that the sinoatrial 5-HT4 receptors function is similar in new-born Camborough piglets and adult Yucatan minipigs. Both porcine breeds are valid models for human atrial 5-HT4 receptors as demonstrated with the antagonist SB 203186.
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1432-0800
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Type of Medium: Electronic Resource
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  • 13
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    Unknown
    London : Periodicals Archive Online (PAO)
    Longman's magazine. 39:229 (1901:Nov.) 78 
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Archives of environmental contamination and toxicology 29 (1995), S. 291-296 
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract Laboratory tests were developed to allow identification of the effects of toxicants on the predator-prey interaction between Hydra oligactis Pallas and Daphnia magna Strauss. Three test methods, which differed with respect to initial Daphnia population, test period, and management of predation level, were used to determine the influence of the organochlorine insecticide lindane on the interaction. The criteria examined were the population structures of the two species. The lindane treatments did not alter the production of Hydra. However, the final population structure of Daphnia was variously affected by the toxicant in the different test systems. The most sensitive endpoint, with a lowest observed effect concentration of 4 μg/L lindane determined after a 14 day exposure period, was increased recruitment of juvenile Daphnia in a test system which incorporated management of the Hydra. The results are compared to previously reported data derived from single species chronic tests, and the suitability of the test methods for hazard evaluation is discussed.
    Type of Medium: Electronic Resource
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Archives of environmental contamination and toxicology 34 (1998), S. 41-47 
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract. The feeding response of juvenile amphipod Gammarus pulex (L.) was investigated following exposure to freshwater pollutants. The method employed is nondestructive, provides a rapid indication of the status of groups of individuals, and is based on a time-response analysis of the consumption of the eggs of Artemia salina and the determination of median feeding times or FT50s. The feeding activity of juvenile G. pulex was found to be a sensitive response criterion for use in assessing the sublethal toxicity of copper, lindane, and 3,4-dichloroaniline (3,4-DCA). Reductions in gammarid feeding activity were identified following 96 hours exposure at 12.1 μg/L copper or 8.4 μg/L lindane and 240 hours exposure at 918 μg/L 3,4-DCA. However, a significant increase was observed in the feeding rate of gammarids that had been exposed for 240 h at 0.09 μg/L lindane in comparison with control values. The increase in feeding rate may be interpreted as a possible stimulatory effect associated with the toxicant action of lindane. Increases in gammarid feeding activity were not determined during the experiments conducted with either copper or 3,4-DCA. A sustained reduction in G. pulex feeding rates may cause growth inhibition and impaired reproduction which have previously been identified as sublethal responses of other freshwater organisms exposed to comparable concentrations of lindane, 3,4-DCA, or copper. The feeding bioassay was also used as a tool in an investigation of species interactions in toxicant systems. The feeding responses of G. pulex, which had been maintained in the presence of Asellus aquaticus (as interacting pairs) and exposed to a range of concentrations of lindane or 3,4-DCA, were recorded and compared. The findings illustrate the complex nature of test systems that integrate the stresses of toxicant and competition. In the lindane test system a reduction in gammarid feeding activity was observed following a 96-h exposure with A. aquaticus at 3.8 and 6.0 μg/L lindane (mean measured concentrations). After a 240-h exposure period a decrease in feeding rate was recorded only for gammarids that had been exposed to 6.5 μg/L lindane, however exposure to very low concentrations of lindane (0.1 and 0.9 μg/L) resulted in a significant increase in gammarid feeding activity. In the experiment conducted with 3,4-DCA the calculation of median feeding times or FT50s of gammarids that had been exposed for 96 and 240 h in the toxicant treatment groups with A. aquaticus was largely precluded (in most groups less than 50% of the A. salina eggs were eaten). However, control group FT50 values were determined on each occasion the bioassay was performed, indicating that a substantial reduction in gammarid feeding activity had occurred in the majority of the 3,4-DCA treatment groups.
    Type of Medium: Electronic Resource
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  • 16
    ISSN: 0948-5023
    Keywords: Acetylcholine Receptor ; Acetylcholinesterase ; Modeling ; Receptor ; Homology ; 3-D Structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Acetylcholine is a ligand for both acetylcholinesterases and nicotinic acetylcholine receptors. Hence, at least some local sequence and structural similarities between the acetylcholinesterases and the receptors which recognize acetylcholine (ACh) might be expected. Peterson [2] produced an alignment of the ACh binding region between these two types of ACh–binding molecules, featuring a number of well conserved residues. The extent of this region of sequence similarity suggests the possible existence of a common ancenstral ACh binding module. To attempt to further validate Peterson′s sequence alignment we have built a homology model of the ACh binding domain of the human neuromuscular nicotinic acetylcholine receptor based on the structure of acetylcholinesterase from Torpedo californica. Using this 3–D model we have examined the residues which were previously shown to interact with the endogenous ligand by various methods (mapping, site–directed mutagenesis). The consistency of such data with the model provides further support for a structural similarity and possibly a divergent evolutionary relationship between the ACh–binding domains of these two classes of proteins. Results suggest that this model may be able to contribute to an understanding of the structure and function of the ACh receptor. Using this case as an example, we propose that 3–dimensional computer modeling can be used as a tool to evaluate distant homologies when adequate experimental data (e.g., site–directed mutagenesis) is available.
    Type of Medium: Electronic Resource
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  • 17
    ISSN: 1432-0495
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Type of Medium: Electronic Resource
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Surgical endoscopy and other interventional techniques 9 (1995), S. 974-976 
    ISSN: 1432-2218
    Keywords: State authorization delays ; Increased cost and morbidity ; Complications of cholelithiasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The impact of delay in elective cholecystectomy caused by preoperative state authorization requirements was retrospectively studied. The Student's t-test was used for statistical analysis. From 10/92 to 5/94, 146 patients were evaluated in an outpatient surgery clinic and elective cholecystectomy was planned. These patients were divided into two groups. Group 1 (101) patients waited for state authorization prior to cholecystectomy while group 2 (45) patients did not need state authorization. Group 1 patients waited an average of 112 days from the time of diagnosis to the time of surgery while group 2 patients waited an average of 21 days (P〈0.001). Group 1 patients were more likely to develop acute complications of cholelithiasis and require admission and urgent cholecystectomy than group 2 patients (22% vs 11%, P〈0.05). Group 1 patients requiring emergent treatment were found to have a longer hospital stay (P〈0.001), longer operative time (P〈0.05), and higher intraoperative blood loss (P〈0.005) than group 1 elective cases. Elective cholecystectomy patients who require state authorization have to wait longer prior to cholecystectomy and frequently develop acute complications of cholelithiasis requiring hospital admission and nonelective surgery. This translates into increased patient morbidity and added cost. State authorization requirements act as a barrier to providing timely care, add to cost, and must be considered in the current deliberations on health care policy.
    Type of Medium: Electronic Resource
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  • 19
    ISSN: 1572-8773
    Keywords: carbonyl iron ; deferiprone (L) ; guinea pig ; iron ; iron chelators ; iron-overload
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The use of the iron chelator deferiprone (L, CP20, 1,2-dimethyl-3-hydroxypyrid-4-one) for the treatment of diseases of iron overload and other disorders is problematic and requires further evaluation. In this study the efficacy, toxicity and mechanism of action of orally administered L were investigated in the guinea pig using the carbonyl iron model of iron overload. In an acute trial, depletion of liver non-heme iron in drug-treated guinea pigs (normal iron status) was maximal (approximately 50% of control) after a single oral dose of L1 of 200 mg kg, suggesting a limited chelatable pool in normal tissue. There was no apparent toxicity up to 600 mg kg. In each of two sub-acute trials, normal and iron-loaded animals were fed L (300 mg kg day) or placebo for six days. Final mortalities were 12/20 (L) and 0/20 (placebo). Symptoms included weakness, weight loss and eye discharge. Iron-loaded as well as normal guinea pigs were affected, indicating that at this drug level iron loading was not protective. In a chronic trial guinea pigs received L (50 mg kg day) or placebo for six days per week over eight months. Liver non-heme iron was reduced in animals iron-loaded prior to the trial. The increase in a wave latency (electroretinogram), the foci of hepatic, myocardial and musculo-skeletal necrosis, and the decrease in white blood cells in the drug-treated/normal diet group even at the low dose of 50 mg kg day suggests that L may be unsuitable for the treatment of diseases which do not involve Fe overload. However, the low level of pathology in animals treated with iron prior to the trial suggests that even a small degree of iron overload (two-fold after eight months) is protective at this drug level. We conclude that the relationship between drug dose and iron status is critical in avoiding toxicity and must be monitored rigorously as cellular iron is depleted.
    Type of Medium: Electronic Resource
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  • 20
    ISSN: 1573-5168
    Keywords: diet ; fish ; hypoxia ; O2 uptake ; spontaneous locomotor activity ; sturgeon ; ω3 fatty acids ; vitamin E
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Adriatic sturgeon (Acipenser naccarii) were maintained on a commercial diet enriched either in long chain polyunsaturated fatty acids of the ω3 series (ω3 LCPUFA) or in saturated fatty acids (SFA). The effects of dietary fatty acid composition on spontaneous locomotor activity in normoxia and hypoxia (O2 tension = 10.5 ± 0.8 kPa), and on oxygen consumption (MO 2) in normoxia, in hypoxia (O2 tension = 6.6 ± 0.8 kPa) and during recovery were then investigated. The effects of adding supplementary vitamin E to the fat-enriched diets were also studied. Dietary fatty acid composition had effects on spontaneous locomotor activity and MO 2 in normoxia. Activity levels were higher in all sturgeon fed extra dietary fats (without vitamin E), when compared with control animals, but fish fed ω3 LCPUFA had a significantly lower MO 2 than those fed SFA, with intermediate MO 2 in controls. In hypoxia, sturgeon ω3 LCPUFA did not alter activity or MO 2 whereas those fed SFA reduced both and controls reduced MO 2. During recovery, both animals fed SFA and controls had a higher MO 2 than sturgeon fed ω3 LCPUFA. The data indicate that fish fed ω3 LCPUFA are more tolerant of hypoxia than controls or those fed SFA, as they did not reduce either activity or MO 2, and consumed less O2 during recovery. Vitamin E supplements modified the effects elicited by dietary fats. All sturgeon fed vitamin E had low activity levels in normoxia and hypoxia. Sturgeon fed vitamin E with ω3 LCPUFA had a higher MO 2 in normoxia than those fed ω3 LCPUFA alone; reduced MO 2 in hypoxia, and during recovery increased MO 2 to a rate higher than that of animals fed ω3 LCPUFA alone. In normoxia, sturgeon fed vitamin E with SFA had a similar MO 2 to those fed SFA alone but did not change MO 2 in hypoxia or during recovery. Thus, the effects of vitamin E were dependent on fat composition of the diet. Vitamin E with ω3 LCPUFA removed the beneficial effects on MO 2 and responses to hypoxia obtained with ω3 LCPUFA alone, but vitamin E with SFA allowed sturgeon to maintain aerobic metabolism in hypoxia, a more effective response than that observed in fish fed SFA alone.
    Type of Medium: Electronic Resource
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