摘要:

Abstract:Vigabatrin (gamma‐vinyl GABA) is a relatively new antiepileptic drug. Vigabatrin increases the concentration of gamma‐aminobutyric acid (GABA) in the brain by inhibiting the major GABA metabolizing enzyme, GABA transaminase. Controlled clinical trials have demonstrated an excellent antiepileptic effect of vigabatrin, especially in the treatment of partial epilepsies. Long‐term evaluations have shown no signs of tolerance development. Vigabatrin decreases the plasma concentration of phenytoin during concomitant therapy, the only drug with which an interaction seems to occur. In general, vigabatrin is well tolerated. Psychotic reactions occur in 3–6% of patients. Other frequent side effects are sedation and weight increase. Chronic vigabatrin intoxication in animals caused development of intramyelinic oedema, appearing as microvacuoles in brain white matter. No microvacuolation has been observed in humans, even after long‐term treatment. Vigabatrin seems a very valuable new antiepile

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00465.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Opening of K+channels in cell membranes with resulting increase in K+conductance, shifts the membrane potential in a hyperpolarizing direction towards the K+equilibrium potential. Hyperpolarization reduces the opening probability of ion channels involved in membrane depolarization and excitation is reduced. K+channel openers are believed to hyperpolarize smooth muscle cells by a direct action on the cell membrane. The best known members of the group are cromakalim, nicorandil and pinacidil, but several new compounds are being evaluated. In addition, it has recently been shown that also clinically well‐known drugs like, e.g. diazoxide and minoxidil exhibit K+channel opening properties. Nicorandil and new compounds containing nitro groups have a dual mechanism of action, also activating guanylate cyclase, an effect that contributes to their cardiovascular effect profile. K+channel openers have a wide range of effects. Some of their properties and actions are summarized, and their present applications and/or potential for future application, in e.g. hypertension, angina pectoris, asthma, bladder instability, and several other disorders are discussed. It is concluded that K+channel openening represents an interesting pharmacological principle with many potential clinical applications. However, most available drugs do not seem to have a sufficient tissue selectivity to be useful therapeutic alternatives. Before the potential of the new members of the group on clinical trials can be properly evaluated, clinical experiences are neede

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00466.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Methods for preparation of labelled ochratoxin A and B are described. The method for preparation of labelled ochratoxin B involves the synthesis of the azide of ochratoxin β via the mixed anhydride and subsequent conjugation to labelled phenylalanine to yield14C‐ochratoxin B. The labelled ochratoxins were injected into male Wistar rats and after different survival times they were sacrificed and subjected to whole body autoradiography. The distribution pattern of ochratoxin A in the rat did not differ from that earlier registered for mouse. The previously known, high susceptibility of rats (and not mice) to ochratoxin A‐induced cancer could thus not be explained by an accumulation of the toxin in specific cells or organs. The distribution patterns of ochratoxin A and B were almost congruent – the only apparent difference being a much longer retention of the labelled ochratoxin A in the blood compared to ochratoxin B, which was much faster excreted. When analyzing tissue extracts for labelled metabolites only the extracts from the rats injected with ochratoxin B were found to contain easily detectable concentrations, while no metabolites of ochratoxin A wer

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00467.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:During the last 5 years, the site of gastrointestinal absorption of inorganic mercury has been attempted identified mainly by experiments using perfused intestinal segmentsin vitroorin situ. The present investigation will discuss the localization of the absorption site for mercuric chloride based on a completely undisturbedin vivoexperimental model in mice. As the mice were allowed to eat their normal diet during the experimental period, the present results would independently add to existing knowledge on intestinal absorption sites for inorganic mercury. The mice were given203Hg labelled mercuric chloride orally, either through stomach tube or in the drinking water, and were killed after various time intervals. Mercury was localized and quantified in various segments of the gastrointestinal tract by gamma‐counting. Time course analysis of the segmental deposition of mercury demonstrated that the deposition mainly takes place in the proximal jejunum and suggested that a larger part of the jejunum than previously reported is involved in absorption of mercury. Using thisin vivomodel, tetraethylthiuram disulfide was demonstrated to increase the intestinal deposition and absorption without changing the site of depositio

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00468.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Protein supplemented diet was protective against the deleterious action of endosulfan on body growth and liver. Hepatomegaly and a reduction of body weight produced concurrently by endosulfan and ethanol were greater in male rats, suggesting that males are more susceptible than female rats to the metabolic stress caused by their interaction. Chronic endosulfan exposure resulted in a prolongation of ethanol sleeping time in female and not in male rats. This finding suggests failure of female rats to metabolize ethanol readily on account of their greater susceptibility than male rats to the hepatotoxic action of endosulfan.

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00469.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Convulsions and pulmonary damage result when animals are exposed to hyperbaric oxygen at pressures above about 300 kPa. Several hydroxyl radical scavengers (namely dimethylsulphoxide, dimethylthiourea and mannitol), the iron chelator desferoxamine and the lipid antioxidant butylated hydroxytoluene were tested for possible protection against such hyperbaric oxygen toxicity. Dimethylthiourea and dimethylsulphoxide prolonged the latency to the first convulsion, but, surprisingly, dimethylthiourea very significantly increased pulmonary damage at both pressures used (515 and 585 kPa). Desferoxamine also slightly increased lung damage at 585 kPa. Other antioxidants did not alter neurotoxicity or pulmonary toxicity induced by hyperbaric oxygen at 515 or 585 kPa. The antioxidants were also tested for their ability to inhibit lipid peroxidation (TBARS formation)in vitro. Desferoxamine (5 and 50 μM), and butylated hydroxytoluene (0.1 mM and 1 mM) greatly inhibited TBARS formation in brain and lung homogenates incubated at 37°. None of the hydroxyl radical scavengers affected TBARS levels in homogenates. There was no correlation between in vitro inhibition of lipid peroxidation andin vivoprotection against oxygen toxicit

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00470.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Aluminium is widely used as an adjuvant in human vaccines, and children can often receive upto 3.75 mg of parenteral aluminium during the first six months of life. We show that intraperitoneal injection of aluminium adsorbed vaccines into mice causes a transient rise in brain tissue aluminium levels peaking around the second and third day after injection. This rise is not seen in the saline control group of animals or with vaccine not containing aluminium. It is likely that aluminium is transported to the brain by the iron‐binding protein transferrin and enters the brain via specific transferrin receptor

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00471.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:2(RS)‐D‐ribo‐(1′, 2′, 3′, 4′‐Tetrahydroxybutyl)thiazolidine‐4(R)‐carboxylic acid (Ribose‐Cysteine, RibCys), a latent form of L‐cysteine, releases the sulfhydryl amino acidin vivoby non‐enzymatic ring opening and solvolysis. The liberated L‐cysteine then stimulates hepatic glutathione biosynthesis. In the present studies, the efficacy of hepatoprotection by RibCys was evaluated to explore its potential utility as an acetaminophen (APAP) antidote. Protection was evaluated in the Swiss‐Webster mouse model both by survival data as well as by quantitative histological criteria of hepatic damage. A dose‐response study showed increased protection with increased intraperitoneal doses of RibCys ranging from 0.5 to 8.0 mmol/kg. RibCys administration 30 min. prior to and up to four hours after the APAP dose showed varying degrees of protection; however, the best protection was seen when RibCys was given shortly after APAP administration. A single RibCys dose given by the intraperitoneal or intravenous route gave better protection than when administered orally; however, RibCys given in three doses, one hour apart, regardless of the mode of administration, offered the best protection after an LD90dose of APAP. Overall, RibCys continues to exhibit promising protective capabilities against APAP hepatotoxicity, which may be capitalized upon

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00472.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:To determine whether caffeine antagonizes the decremental effects of triazolam and zopiclone on human performance, oral single doses of 0.250 mg triazolam, 7.5 mg zopiclone, or respective placebos, with and without 300 mg caffeine, were given to parallel groups of student volunteers in two double‐blind studies. Objective tests and subjective visual analogue ratings were done at baseline and 30 min. and 90 min. after the intake. In Study I, triazolam produced drowsiness at 30 min. but did not differ from the placebo in other tests. Caffeine induced alerting effects in various tests and differed from triazolam in some (digit substitution, drowsiness, calmness, mental slowness) but not all variables measured. Caffeine and triazolam were interpreted as being antagonists. In Study II, zopiclone impaired digit substitution and flicker fusion, produced exophoria and lowered systolic blood pressure. Caffeine differed from zopiclone in several test functions, but it also differed from caffeine + zopiclone whereas zopiclone differed from caffeine + zopiclone only in two tests (Maddox wing, systolic blood pressure). Thus, zopiclone counteracted the effects of caffeine more easily than caffeine counteracted the decremental effects of zopiclone. We conclude that triazolam may not differ importantly from diazepam as regards their antagonism towards caffeine, whereas further research on the antagonism between zopiclone and caffeine needs to be don

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00473.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:The influence of high doses of oral nitrendipine on the hypophyseal‐thyroid axis and on peripheral thyroxine metabolism was studied in baboons. Administration of 320 mg oral nitrendipine per kg body weight (b.wt.) for three months caused a hypothyroid state with decreased values for thyroxine and reverse triiodothyronine, elevated TSH, but unchanged triiodothyronine; the lower doses investigated (24 and 48 mg/kg b.wt.) were without any effect. High doses of nitrendipine concomitantly increased hepatic 5′‐deiodinating activity by a rise in Vmax,which could be attributed to an increase in the deiodinating enzyme content. Normal T3serum levels in the presence of low T4serum concentrations under high dose nitrendipine can be ascribed, at least in part, to the enhanced peripheral 5′‐dei

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00474.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY