摘要:

AbstractEffects of tilisolol, a β‐adrenoceptor‐blocking agent having an ATP‐sensitive potassium channel‐opening property, on ischaemic myocardial acidosis were studied and compared with those of other β‐adrenoceptor‐blocking agents.Ischaemia was induced by ligating the left anterior descending coronary artery in anaesthetized dogs. Myocardial pH was measured by a tissue pH monitor. Drugs (tilisolol, 0.2 mg kg−1; propranolol, 1 mg kg−1; amosulalol, 0.3 mg kg−1and nipradilol, 0.3 mg kg−1) were injected intravenously 5 min before ischaemia. All drugs decreased heart rate. Amosulalol and nipradilol decreased arterial pressure. The myocardial pH in the saline‐treated group decreased significantly after 30 min of ischaemia. Each drug attenuated the ischaemiainduced myocardial acidosis. Magnitude of the effects was tilisolol>propranolol>amosulalol ≥ nipradilol. The attenuation of myocardial acidosis with tilisolol was partially abolished by glibenclamide.In conclusion, tilisolol improved the ischaemia‐induced myocardial acidosis, and its ATP‐sensitive potassium channel‐opening action may partially c

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00619.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractDeramciclane is a novel structure among anxiolytic agents. Pharmacokinetic studies in different species indicated the possibility of strong protein binding. The binding of deramciclane to plasma from man, dog, rabbit, mouse and rat was investigated by equilibrium dialysis.Binding isotherms for human and dog plasma exhibited both saturable and non‐saturable components, while binding to rabbit, rat and mouse plasmas appeared to be non‐saturable. The differences could be attributed to the different α1‐acid glycoprotein (AAG) affinities. The strong binding of deramciclane in human plasma (nK = 1.6 times 106M−1) could be referred to the AAG component, and could be inhibited by several ligands known to associate with this protein. The high affinity and saturable binding of deramciclane to an acute phase component of the human plasma (AAG) necessitates careful dosage during therapeutic app

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00620.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractWe have studied the endotoxin retention capabilities of two filters claimed to be suitable for 96‐h use. The filters were, a positively charged nylon membrane filter (Pall Biomedical Ltd) and a positively charged polysulphone membrane filter (Gelman Sciences Ltd).Simulated patterns of intravenous therapy that would be used over a 96‐h period were set up. The administration sets were injected with either a 1‐mL bolus of anEscherichia coli(108cells suspension in 5% glucose or in a parenteral nutrition solution. After 96 h, 2‐mL filter effluent samples were tested for endotoxin using the Limulus amoebocyte lysate test (sensitivity: 0.015 endotoxin units (EU) mL−1).In theE. coliin 5% glucose experiments, no endotoxin was found downstream of the positvely charged nylon membrane filters, but large amounts of endotoxin (5 min=>10.0 EU mL−1, 72 h = 0.153 EU mL−1) were found downstream of the positively charged polysulphone membrane filters. After challenging the filters with endotoxin in parenteral nutrition solution, again no endotoxin was detected downstream with the positively charged nylon membrane filters, but one of the positively charged polysulphone membrane filters allowed endotoxin to pass through after 48 h (4.45 EU mL−1).These results indicate that only the positively charged nylon membrane can be safely used for up to 96 h without detecting the presence of endotoxin downstrea

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00621.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe dependency of in‐vitro and in‐vivo drug release from a self‐setting bioactive calcium phosphate cement containing 0.5% oestradiol on the plasma calcium level in rats was investigated.The in‐vitro release profiles from drug‐loaded calcium phosphate cements with various calcium levels in simulated body fluid, indicated that the release rate decreased with increasing calcium concentration in dissolution media. After subcutaneous implantation of drug‐loaded cement in healthy and vitamin D‐deficient ovariectomized rats, oestradiol released in the diseased rat, with low plasma calcium level, was significantly higher than that in the healthy rat, indicating that oestradiol release from the cement depended on the plasma

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00622.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThis report presents the results of studies of the anti‐malarial activity of a de‐novo synthesized quinolone (Q/1) and the antibiotic tetracycline in mice infected withPlasmodium berghei.P. berghei‐infected mice received either Q/1 2‐4‐diamino‐10‐methyl‐pyrimido[4,5‐b]quinolin‐5(10H)‐one (125 mg kg−1, i.m.), tetracycline (250 mg kg−1, i.m.) or a combination of the drugs (Q/1 125 mg kg−1+ tetracycline 250 mg kg−1, i.m.) in 0.1 mL vols. Parasitaemias from tail blood were determined over 17 days. Mice receiving Q/1 only, did not have a parasitaemia significantly different from the control group, but the Q/1‐treated mice had a longer survival time (15 vs 10 days). Mice receiving tetracycline showed similar results to the Q/1 group. However, the animals treated with the Q/1 + tetracycline combination showed a significant decrease in the mean parasitaemias compared with the control and had a longer survival time (17 days).These results show the potential for de‐novo synthesized quinolone derivatives, associated with other drugs,

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00623.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractPanasorb tablets were prepared from the waste of plant cell tissue culture ofPanax ginseng(C. A. Meyer) by recently developed technology. These tablets may be used in medicine as non‐specific absorbents with a broad spectrum of pharmacological activity. The influence of moisture, granule size and compression pressure on the technological parameters of the tablets was investigated.Regression equations for the time of disintegration, mechanical strength and friability of tablets, by statistical processing of experimental results, were obtained and were found to be non‐linear functions. Moisture content and compression pressure are the most significant parameters in the tablet making process. The influence of granule size can be considered insignificant.It was established that the time of disintegration and mechanical strength of tablets are correlated with an increase in compression pressure. The optimum compression pressure was observed in the interval 140‐180 MPa. The optimum moisture content of the granules was

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00624.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractWe report an in‐vitro inhibitory effect of gossypol on eightTrichomonas vaginalisisolates.Metronidazole is an effective medication againstT. vaginalis, but there is an increasing number of reports ofTrichomonasresistance to the drug. Subsequently, alternative therapies need to be investigated. The pharmacological properties of gossypol have been studied extensively because of its toxicity to livestock, its antifertility effects in man, and its activity against diverse pathogenic agents.EightT. vaginalisisolates were treated with either variable concentrations of gossypol (0‐100 μm) or metronidazole (0‐1.0 μM). The effective IC50 range for gossypol was from 24.39 to 38.77 μM (metronidazole: 0.15‐0.40 μM) with an average of 31.9 μM (metronidazole: 0.27 μM). No gossypol‐resistantTrichomonasstrains were detected.Gossypol, formulated as pesky, is used safely and successfully as an antifertility drug in man. The effective spermicidal dose of this drug (50 μM), and the antitrichomonas IC50 doses are comparable. This polyphenol also has a clear inhibitory effect against herpes and human immunodeficiency virus. Its effectiveness as an antitrichomonic medication could be immediately evaluated, considering that this drug is already used in man. Since gossypol is an abundant by‐product of the cottonseed industry, it may be produced at r

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00625.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractDihydropteridin reductase (EC 1.6.99.7) is an essential enzyme in the maintenance of tetrahydrobiopterin, which is a natural cofactor for nitric oxide synthase, alkyl glycerylmonooxygenase, and biosynthesis of catecholamines and 5‐HT. The study was undertaken to evaluate dihydropteridin reductase activity on blood spots from patients with several haematological malignancies, Behçet's disease, rheumatoid arthritis and familial Mediterranean fever.Our results suggest that dihydropteridin reductase activity can be affected by either chemotherapeutics or by pathological conditio

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00626.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractWe have previously shown that an antisense phosphorothioate oligonucleotide, erbB1AS15 (PS), targeted against the initiation codon of the epidermal growth factor receptor (EGFr) mRNA, inhibited receptor tyrosine kinase activity via a non‐antisense mechanism in A431 cells. The aims of this study were to evaluate the effect of this oligonucleotide on A431 cells in the presence of exogenous stimulation with high concentrations of the EGF ligand and to further elucidate the mechanism of action of erbB1AS15 (PS).The morphological effects of EGF stimulation were monitored in A431 cells in culture. The results show that the rapid rounding induced by stimulation with 500 ng mL−1EGF in A431 cells was modulated by the erbB1AS15 (PS) oligonucleotide. The presence of the oligonucleotide reduced the initial rapid morphological change and increased the rate at which the cells returned to normal following removal of EGF. Control oligonucleotides had no effect, suggesting that the morphological effects of erbB1AS15 (PS) were sequence dependent. The possibility of a site of action at the level of the ligand was discounted by band shift analysis of radiolabelled oligonucleotide in the presence of excess EGF. These results therefore indicate that the oligonucleotide is acting at a point in the EGF‐mediated signal transduction pathway that ultimately leads to these cytoskeletal changes, probably as a result of modulation of downstream phosphorylation.These data, along with the longer‐term morphological change in the A431 cells caused by erbB1AS15 (PS) in the absence of EGF stimulation, demonstrate a potent non‐antisense mediated activity of a phosphorothioate oligon

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00627.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractWistar rats were fed chow supplemented with 1% (w/w) aspirin for one month. At 3, 7, 14, 21 and 30 days of treatment, heparinized blood was collected. ATP, Na+, K+levels, glucose utilization of erythrocytes and inorganic phosphate, Na+, K+, salicylate levels of plasma were determined.Erythrocyte ATP and plasma phosphate levels were decreased following aspirin treatment. ATP decrement caused erythrocyte K+level to diminish significantly. Plasma Na+and K+levels were not effected by aspirin treatment. In addition, the decrease in ATP levels induced erythrocyte glucose utilization.It was concluded that the therapeutic dose of aspirin in man, gave rise to a decrease in the energy production and an impairment of energy utilizing events in erythrocytes in rats (the therapeutic serum aspirin concentration in man is 25‐40 mg dL

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00628.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY