摘要:

AbstractHistamine functions as a neurotransmitter in the central nervous system (CNS), and H2‐receptor activation can modulate the activity of the CNS. H2‐receptor antagonists are known to penetrate the blood‐brain barrier and to cause neuropsychiatric effects. It appears that interactions with CNS H2‐receptors may account for many of these effects, although receptor interactions unique to certain H2‐antagonists may also pl

ISSN:0272-4391    

DOI:10.1002/ddr.430170202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractAlcohol and water extracts from 20 edible fungi species belonging to the following genera—Agaricum, Armillaria, Boletus, Collybia, Coriolus, Cortinfrius, Flammulina, Ganoderma, Hirneola, Lentinus, Lyophyilum, Pleurotus, Sarcodon, Tremella, and Tricholoma— were added to primary culture of cells isolated from atherosclerotic lesions of human aorta to ascertain their influence on the major cellular manifestations of atherosclerosis. Thirteen of the 20 tested extracts were antiatherosclerotic in culture, that is, they caused the decrease in the cellular cholesterol level and/or the inhibition of cellular proliferation ([3H]thymidine incorporation). The antiatherogenic (prophylactic) action of mushroom extracts was also tested using cell culture. The extracts were added to the primary culture of normal intimal cells, which had been stimulated by atherogenic serum from coronary heart disease (CHD) patients to undergo atherogenic transformation (increase in total cholesterol and stimulation of proliferation). Ten of the 20 tested extracts displayed antiatherogenic as well as antiatherosclerotic effects. Four mushroom species were chosen for the study of antiatherosclerotic effects in vivo. Cultivation of “atherosclerotic” cells during 24 hr in the presence of serum from healthy subjects who had had mushroom meals resulted in a 21–30% decrease in the cellular cholesterol level. The atherogenic serum obtained from CHD patients after dietary mushroom consumption partly (30–41%) lost its ability to increase the cellular cholesterol content. The current study presents data suggesting that some mushroom species may be useful as dietary supplements in the prevention and therapy of athe

ISSN:0272-4391    

DOI:10.1002/ddr.430170203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractSC‐40230, α‐[2‐[acetyl(1‐methylethyl)amino]ethyl]‐α‐(2‐chlorophenyl)‐1‐piperidinebutanamide, a new class I antiarrhythmic agent, was tested for efficacy against coronary ligation‐induced arrhythmias and ouabain toxicity arrhythmias in dogs. Doses of 9mg/kg i.v. and 15, 25, and 35 mg/kg p.o. significantly reduced ectopic rate in conscious dogs that had undergone ligation of the left anterior descending coronary artery 24 hr prior to testing. Plasma concentrations of SC‐40230 ranging from 3 to 9 μg/ml corresponded with ectopic rate reductions of 10–82% in the coronary ligation model. SC‐40230 was well tolerated at all doses tested in the conscious dogs. A 5 mg/kg i.v. dose of SC‐40230 converted ouabain‐induced ventricular tachycardias to normal sinus rhythm in anesthetized dogs. The antiarrhythmic effect of SC‐40230 in the ouabain toxicity model was reversed by large (⪇ 240 U) doses of insulin. The experiments described in this study demonstrated that SC‐40230 is a well‐tolerated new class I antiarrhythmic agent with intravenous and oral effec

ISSN:0272-4391    

DOI:10.1002/ddr.430170204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractPropranolol causes airway hyperreactivity to agonists or antigenic challenge in vivo, but its mechanisms are still debated. In this study we found that the addition of propranolol (10 μ/ml) to lung parenchyma strips from sensitized guinea pigs enhanced the sensitivity and maximum contraction to antigenic challenge (ovalbumin, 0.01–100 μ/ml) and the sensitivity to histamine (1 × 10−7to 1.7 × 10−4M), determined through concentration‐response curves. In contrast, tracheal chains from sensitized guinea pigs were unaffected. These results in in vitro preparations strongly suggest that, at least in lung parenchyma tissue, other mechanisms different from beta‐blockade are present in propranolol‐induced airway

ISSN:0272-4391    

DOI:10.1002/ddr.430170205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to compare the effects of a peripherally selective (L‐659,066) vs. a centrally and peripherally active (L‐657,743; MK‐912) α2‐adrenergic antagonist on murine plasma glucose and insulin levels following fasting or administration of hyperglycemic agents (α2‐adrenergic agonists, glucose). The intravenous administration of L‐657,743 or L‐659,066 alone did not cause major alterations in plasma glucose or insulin levels. Pretreatment of mice with either of these agents, however, at selective α2‐adrenoceptor blocking doses (0.3–3 mg/kg) prevented the elevations of plasma glucose levels induced by the α2‐adrenoceptor agonists clonidine or 3,4‐dihydroxyphenylimino‐2‐imidazoline (DPl). Prazosin, an α1‐adrenergic antagonist, did not alter clonidine‐induced elevations of plasma glucose levels. Pretreatment of fasted mice with L‐657,743 or L‐659,066 (1 mg/kg) 5 min before receiving intravenous glucose resulted in higher plasma insulin levels and improved glucose tolerance compared to saline‐pretreated animals. Moreover, both α2‐adrenergic antagonists enhanced the acute insulin response to glucose. These findings indicate that, under conditions of hyperglycemia, insulin release is enhanced by the blockade of peripheral α2‐adrenoceptors α2‐Adrenoceptor antagonists, such as L‐657,743 or the peripherally selective agent L‐659,066, may prove effecti

ISSN:0272-4391    

DOI:10.1002/ddr.430170206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractLocal anti‐inflammatory activities in the carrageenan (CGN)‐induced pleurisy model are reported for steroid‐21‐oate esters derived from prednisolone. Following administration of equipotent doses (per rat) of prednisolone (P),.5mg; methyl 17,20α‐acetonidodihydroprednisolonate (P4AC), 1 mg; methyl 20β‐dihydroprednisolonate (P4B), 1.3 mg; methyl 20α‐dihydroprednisolonate (P4A), 5.8 mg; and methyl 17,20β‐acetonidodihydroprednisolonate (P4BC), 6 mg, effects of the steroids on exudate volume, leukocyte recruitment, and enzyme levels of cell‐free exudates and washed exudate cells were assessed. All derivatives tested significantly inhibited emigration of neutrophils (PMNs) and monocytes (MNs). Steroid treatment with the β‐isomers reduced exudate volumes by 41% and 56% for P4B and P4BC, respectively. In 5 hr neutrophilic exudates, free β‐glucuronidase levels were reduced by 43% by either P4B or P4AC treatments. Of the derivatives tested P4B and P4AC treatments resulted in the greatest reduction of free lysozyme levels. Activities of membrane‐bound γ‐glutamyl‐transferase (GGTP) in exudate cell pellets were reduced following treatment with P and the 20 alpha‐epimers P4AC and P4A. Systemic effects assessed as decreases in plasma corticosterone or suppression of circulating lymphocytes were noted only following P treatment. These results suggest that 1) the locally active steroid‐21‐oate esters act at the site of inflammation by inhibiting PMN and MN infiltration in a manner congruous with conventional steroids, 2) steroid stereochemical configuration plays a role in effects on exudate volumes and GGTP activities, and 3) due to the absence of systemic effects, the steroid‐21‐oate esters

ISSN:0272-4391    

DOI:10.1002/ddr.430170207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractLinogliride fumarate, a structurally novel oral hypoglycemic compound, was tested in the neonatal streptozotocin‐induced rat model of non‐insulin‐dependent diabetes mellitus (NIDDM) [Weir et al.:Diabetes30:590–595, 1981], and its antihyperglycemic effects were compared to those of representative first and second generation sulfonylureas. Two‐day‐old male Sprague‐Dawley rats (STZ) were injected with the beta cell toxin, streptozotocin (90 mg/kg i.p.); male littermates injected with citrate buffer served as controls (CTL). By 8 weeks of age, blood glucose of fed STZ rats was significantly elevated compared to that of CTL animals (>300 mg/dl vs.<110 mg/dl, respectively) and, in response to an oral glucose (1 g/kg) challenge, 18 hr fasted STZ rats exhibited marked glucose intolerance. Linogliride fumarate (10–100 mg/kg p.o.) significantly lowered blood glucose in 18 hr fasted STZ rats and produced a dose‐dependent improvement of oral glucose tolerance. Linogliride fumarate (ED30= 12.5 mg/kg) was approximately six times as potent as tolbutamide (ED30= 72.1 mg/kg) in improving oral glucose tolerance in STZ rats, while glyburide (0.5–2.5 mg/kg p.o.) and glipizide (2.5 mg/kg) were ineffective. This rat model of NIDDM may be useful for evaluating new hyp

ISSN:0272-4391    

DOI:10.1002/ddr.430170208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractAttenuation of the morphine withdrawal syndrome by the combination treatment of morphine and protein/nucleic acid synthesis inhibitors was investigated in rats. Groups of rats were treated twice daily with gradually increasing doses of morphine (4–28 mg/kg) in combination with a protein/nucleic acid synthesis inhibitor (actinomycin D, chloramphenicol, cycloheximide, cytarabine, or tetracycline) for 14 days. Withdrawal was precipitated by naloxone on day 15 and the withdrawal manifestations were scored on a weighted basis for mild, moderate, and severe signs. The mild withdrawal signs were significantly decreased by cytarabine and tetracyline whereas the other combination‐treated groups were only slightly decreased. The moderate and serve withdrawal signs for all combination‐treated groups were significantly suppressed compared to the morphine‐treated group. Therefore, attenuation of the morphine withdrawal syndrome by these protein/nucleic acid synthesis inhibitors supports an involvement of macromolecules in the development of physical dep

ISSN:0272-4391    

DOI:10.1002/ddr.430170209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe effects of GABAergic agents (GABA, fengabine, baclofen) and alpha2agonists (clonidine and BHT‐920) on isoniazid (INH)‐induced convulsions in mice were studied. All the GABAergic agents and alpha2agonists employed in the study provided significant protection against INH‐Induced convulsions and death. The protective effects of alpha2agonists were sensitive to blockade by yohimbine or idazoxan. When a subeffective dose of alpha2agonist or GABAergic agent was concomitantly administered with a subeffective dose of diazepam, a potentiation of the anticonvulsant effect of diazepam was observed. Alpha2agonists through GABAergic mechanism offer protection against INH‐induced seizures

ISSN:0272-4391    

DOI:10.1002/ddr.430170210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractRats were given daily 1‐hr sessions in photocell cages until baseline locomotion stabilized.d‐Amphetamine 0.5–2.0 mg/kg p.o. significantly increased locomotion. Chlorpromazine 2.5–20 mg/kg p.o. and pentobarbital 5.0–20 mg/kg p.o. significantly decreased locomotion.N= 4 per drug. Results demonstrate the appropriateness of using chronic single subjects to assess the effects of drugs on locomotion. An attempt to generate cumulative dose‐effect curves in rats run once a week was less successful because of intrasubject variability. The method could also be used for multiple drug studies in lesioned or cannulated p

ISSN:0272-4391    

DOI:10.1002/ddr.430170211

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY