摘要:

AbstractCryptosporidiumsp. andIsosporasp. are coccidian protozoans taxonomically related toToxoplasma gondiiandPlasmodiumsp. Although associated with many animal species, these pathogens are also the causative agents of cryptosporidiosis and isosporiasis, 2 invasive opportunistic infections in humans. In immunocompetent hosts, the infections are usually self‐limited, flu‐like gastrointestinal disorders which resolve spontaneously. In immunocompromised patients, however, cryptosporidiosis is a severe, debilitating, and prolonged illness, with high morbidity and no known therapy effective against it. Spiramycin has been proven largely ineffective. In recent years, however, the use of immunotherapy is being actively pursued as one potentially useful approach for the treatment of cryptosoporidiosis. Azithromycin, a new macrolide antibiotic, has also shown promise in preclinical studies. In the case of isosporiasis, the combination of trimethoprim and sulphamethoxazole has been found to be effective, although AIDS patients have shown a high rate of relapse and, therefore, the need for suppressive maintenance therapy. © Wiley‐Lis

ISSN:0272-4391    

DOI:10.1002/ddr.430280402

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

年代:1993

数据来源: WILEY

摘要:

AbstractAn animal model of failed coronary angioplasty was used to evaluate the effect of intracoronary diltiazem on regional ischemia and the degree of myocardial necrosis. Ischemia was produced in closed‐chest, pentobarbital‐anesthetized male mongrel dogs by inflation of 2.5–3.0 mm diameter balloons introduced under fluoroscopy into the left anterior descending or left circumflex coronary arteries. Animals were randomly assigned to control or diltiazem administered at the time of balloon inflation. Diltiazem, 900 μg/kg, was administered in divided doses through the lumen of the angioplasty balloon catheter. Diltiazem reduced the mean arterial pressure by 27 ± 6 mm Hg and blunted tachycardia following occlusion, which was also seen in controls. After 50 min of ischemia, a left thoracotomy was performed, and the left atrium was cannulated for injection of radiolabeled microspheres at 70 min. The animal was then reperfused by deflating the balloon. Regional segment function showed similar dyskinesis in the ischemic area of both groups. At 4 h the animal was sacrificed and the heart was removed for measurement of the area at risk and infarct size using a dual staining technique. Infarct size, when determined as the percent of the area at risk, was significantly reduced in diltiazem treated animals, 9 ± 2%, as compared to control animals, 22 ± 5%. Regional myocardial blood flow did not differ between groups. Therefore, intracoronary diltiazem produced a significant reduction in myocardial injury. This intervention may be useful to delay cell death in the setting of failed coronary angioplasty. © Wiley

ISSN:0272-4391    

DOI:10.1002/ddr.430280403

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe antiviral dn cytotoxic activity of SP‐303, a naturally occurring polyphenolic polymer (average M.W. = 2,100 daltons) isolated from a Euphorbiaceae shrub, was evaluated in tissue culture. The compound exhibited selective antiviral activity (ratio IC50/EC50≥10) against parainfluenza virus type 1, respiratory syncytial virus, influenza A viruses, and influenza B viruses; marginal selective antiviral activity (IC50/EC50ratio>2 to<10) against parinfluenza virus type 3; and no selective antiviral activity (IC50/EC50ratio ≤1) against measles virus or adenovirus type 5. Hemagglutination and other studies suggested that SP‐303 may at least partially inactivate virus by direct interaction with virus or host cell lipid membranes. © Wiley

ISSN:0272-4391    

DOI:10.1002/ddr.430280404

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

年代:1993

数据来源: WILEY

摘要:

AbstractDexmedetomidine is a potent, specific, and selective α2‐adrenoceptor agonist undergoing clinical trials as an adjunct to anesthesia. It may also have potential use in the treatment of glaucoma. In anesthetized rats and rabbits, dexmedetomidine induced marked bradycardia, rats being 5 times more sensitive than rabbits. In conscious rabbits, the bradycardia induced by dexmedetomidine was even less apparent; a dose of 40 αg/kg ws needed to consistently slow the pulse. Higher doses of dexmedetomidine induce a direct vasoconstrictor response in the anesthetized animals, in the case rabbits were 9 times less sensitive than rats. In both tests the anesthetized rat better mimicked the sensitivity of humans to dexmedetomidine. Thus, it should be remembered that in ocular pharmacology, where the rabbit is the prevalent experimental animal used, this species is relatively insensitive to the cardiovascular effects of this novel α2‐adrenoceptor agonist. © Wiley‐

ISSN:0272-4391    

DOI:10.1002/ddr.430280405

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

年代:1993

数据来源: WILEY

摘要:

AbstractS 9977 (1,3,7‐trimethyl 8‐[3‐(4‐diethylaminocarbonyl‐l‐piperazinyl)1‐propyl]‐3,7‐dihydro(1H)2,6‐purinedione hydrochloride) is a methylxanthine derivative lacking activity at adenosine receptors and having no phosphodiesterase inhibitory action, but which has been reported to enhance cholinergic function. In mice 0.06 mg/kg ip increased, whereas 0.25 and 1 mg/kg ip decreased, spontaneous alternation in a T‐maze. Doses of 0.03 and 0.06 mg/kg ip improved acquisition and retention of a spatial discrimination task when administered on the test days. The dose of 0.06 mg/kg ip was without effect on subsequent retention when given immediately post‐acquisition, suggesting it was without effect on storage processes. When it was administered for 14 days prior to testing 0.06 mg/kg ip retained its effects on acquisition and retention of the discrimination task, but no longer had significant effects on spontaneous alternation. In rats, there was no effect on between‐day habituation of exploration or on acquisition of a working and reference memory task with a 24 h intertrial interval. However, 0.06 mg/kg ip significantly improved retention of this task and 0.12 mg/kg ip significantly improved acquisition when a 48‐h intertrial interval was used, mainly due to a reduction in working memory errors. In a test of reference memory in a helical maze 0.03 mg/kg ip improved acquisition. These results suggest that low, but not high, doses of S 9977 can improve acquisition in tasks relying on both working and reference memory and also can improve performance on retention tasks. The results are discussed with reference to the effects of S 9977 in enhancing cholinergic

ISSN:0272-4391    

DOI:10.1002/ddr.430280406

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

年代:1993

数据来源: WILEY

摘要:

AbstractPemedolac Na, 1‐ethyl‐1,3,4,9‐tetrahydro‐4‐(phenylmethyl)‐pyrano [3,4‐b] indole‐1‐acetic acid sodium salt, exhibited equipotent analgesic effects after oral, iv, and im administration, suggesting that it is well absorbed. In mouse writhing models, the ED50values ranged from 0.3 mg (0.81 μmol)/kg (vs. acetylcholine) to 4.3 mg (11.6 μmol)/kg (vs. paraphenylbenzoquinone [PBQ]). In the rat Randall‐Selitto model, the ED50o the compound was approximately 0.001 mg (2.7 nmol)/kg, with a flat dose response curve. The peak effects lasted for 7–9 h, 10–18 h, and 5 h following oral, im, and iv injections, respectively. Intracerebroventricular (i.c.v.) injections of pemedolac Na inhibited the PBQ‐induced writing in mice with an ED50of 43.5 μg (0.12 μmol)/mouse, and this effect was not antagonized by naloxone. It was inactive in the hot plate and tail flick tests, demonstrating that pemedolac Na does not act via an opiate mechanism. These results indicate that pemedolac Na is a viable parenteral and oral analgesic, typified by high analgesic potency, a rapid onset and long duration of action, and an extremely wide sa

ISSN:0272-4391    

DOI:10.1002/ddr.430280407

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

年代:1993

数据来源: WILEY

摘要:

AbstractResponsiveness of the cardiovascular system to the effects of vasoactive agents can vary with age. The endogenous metabolite adenosine has negative chronotropic, inotropic, and hypotensive effects. The purpose of this study was to determine if the effects of exogenously administered adenosine and the adenosine A1receptor antagonist 1,3‐di‐n‐propyl‐8‐(hydroxyphenyl) xanthine (NPC 205) vary with age. The effects of adenosine on mean arterial blood pressure (MABP), heart rate, and cardiac contractility (LV dP/dt) were investigated in two groups of guinea pigs: a young group (3–4 weeks) and an older group (72–75 weeks). In vivo, the older animals were shown to be significantly more sensitive to the negative inotropic, chronotropic, and hypotensive effects of adenosine, whereas the responses to R‐N6‐phenylisopropyladenosine (R‐PIA), a metabolically stable analog of adenosine, were similar in both age groups. In vitro, right atria from young (3–4 weeks) and old (72–75 weeks) guinea pigs exhibited no age‐related differences in the sensitivity to the negative chronotropic effects of adenosine or R‐PIA. Younger animals were more sensitive to the positive inotropic effects of the adenosine A1receptor antagonist, NPC 205. In addition, basal heart rates were significantly lower in the older group of animals. It may therefore be concluded that there age‐related effects of adenosine. Furthermore, comparison of the effects of adenosine to the effects of the stable analog R‐PIA and the adenosine antagonist NPC 205 suggests that these differences may be due to changes in adenosine metabol

ISSN:0272-4391    

DOI:10.1002/ddr.430280408

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe effect of two nootropic drugs, oxiracetam and aniracetam, on cholinergic neurotransmission in vivo was investigated in the rat by means of the transversal microdialysis techique. The basal release of acetylcholine (ACh) from the hippocampus and parietal cortex was 2.93 ± 0.17 and 3.10 ± 0.18 pmol/min (mean ± s.e.m.), respectively, and remained stable for at least 3 h, while the initial efflux of choline was 51.9 ± 2.6 and 42.8 ± 6.4 pmol/20 min (mean ± s.e.m.), respectively, and decreased by about 50% during the first 60 min of collection. Oxiracetam, tested at doses of 50, 100, and 300 mg/kg ip, elicted a 63% increase in ACh release from the hippocampus at the dose of 100 mg/kg only. This effect of oxiracetam was inhibited by perfusion with tetrodotoxin (TTX), 5 × 10−7M. In oxiracetam‐treated rats the decrease in choline efflux was less pronounced than in controls (‐23% of the initial value) at the dose of 100 mg/kg. Aniracetam (100 mg/kg, orally) elicited a sustained increase of ACh release from the hippocampus (+ 58%, 120 min after the administration), without affecting choline efflux. Doses of 50 and 300 mg/kg, orally, of aniracetam were ineffective. Oxiracetam and aniracetam (50 and 100 mg/kg) neither modified the output of ACh or choline from the parietal cortex nor induced gross behavioral changes. These results indicate that oxiracetam and aniracetam could act on cognitive processes by stimulating the hippocampal cholinergic pathways. © Wi

ISSN:0272-4391    

DOI:10.1002/ddr.430280409

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe efficiency of the transdermal penetration of physostigmine through the guinea‐pig skin, in a vehicle containing propionic acid, was studied in the course of developing a transdermal physostigmine pad for the potential treatment of Alzheimer's disease patients. In an attempt to improve drug penetration, the addition of various concentrations of oleic acid(0.5–5%) was tested. The study included histological examination of skin biopsies from application site. The addition of 0.5% oleic acid to the vehicle enhanced the permeation of physostigmine and shortened the time needed to reach steady state levels of blood cholinesterase inhibition, without any damage to the skin. Stable values of physostigmine concentration and of cholinesterase inhibition were measured both in blood and in brain up to 72 h. A high correlation was found between physostigmine concentration in the plasma and cholinesterase inhibition in whole blood samples (r = 0.99 for the values measured up to 48 h). A lower correlation was found between physostigmine concentration and cholinesterase inhibition in the brain (r = 0.57). In a vehicle containing up to 1% oleic acid, physostigmine was stable for at least one month. Oleic acid concentrations higher than 1%, while increasing the flux of the drug through the skin, resulted in considerable skin damage. © Wiley‐Lis

ISSN:0272-4391    

DOI:10.1002/ddr.430280410

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

年代:1993

数据来源: WILEY

摘要:

AbstractAn extensively washed membrane preparation was used to measure the noncompetitive binding site of the N‐methyl‐D‐aspartate (NMDA) receptor complex with [3H]‐1‐[1‐(2‐thienyl) cyclo‐hexyl]piperidine ([3H]‐TCP). Addition of glutamic acid (Glu) or Glu + glycine (Gly) increased the binding of [3H]‐TCP, reflecting that the NMDA receptor ion channel was opened by these compounds. [3H]‐TCP binding was also increased by various 2‐amino‐ω‐phosphonoalkanoic (AP) compounds, of which 2‐amino‐4‐phosphonobutanoic acid (AP4) was the most effective. The effects of AP compounds were also observed in the presence of Gul. However, in the presence of Gly, or in the presence of Glu + Gly, 2‐amino‐5‐phosphonopentanoic acid (AP5) and 2‐amino‐7‐phosphonoheptanoic acid (AP7) inhibited the binding. The enhancing effect of AP4 was also inhibited by these compounds. Our conclusion is that AP compounds exert complex effects: they bind to and effect the NMDA receptor complex ion channel not only via the competitive binding site but may also interact with the po

ISSN:0272-4391    

DOI:10.1002/ddr.430280411

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

年代:1993

数据来源: WILEY