ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb01881.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb01882.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:In order to examine the intestinal absorption of chloral hydrate (CH), free trichloroethanol (F‐TCE) and trichloroacetic acid (TCA), an intestinal circulation system in dogs was developed using jejunal, ileal and colonic loops, and solutions of CH, F‐TCE and TCA were circulated within them. The concentrations of these substances and their metabolites in the serum, urine, bile and circulates were then measured. In all groups, the fraction of water absorbed from the intestine was about 10% of the administered volume two hours after administration. The absorbed fraction of CH was about 50% in the jejunum and ileum, and about 40% in the colon. The absorbed fraction of F‐TCE was about 60% in the jejunum, 5(Mo%0 in the ileum and about 40% in the colon, while the figures for TCA were about 40–50%0 in the jejunum and about 3040% in the ileum and colon. The combined biliary and urinary excretion ratios of the administered substances and their respective metabolites to the total amounts absorbed from the intestine were about 25–30. for F‐TCE, 10–15. for CH and 0.1‐0.2% for TCA in all parts of the intestine two hours after

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb01883.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:Male Sprague Dawley rats were exposed to inhalation of n‐C9 to n‐CI3 alkanes close to air saturation at 20$dG (4438, 1369, 442, 142 and 41 p.p.m., respectively) for 8 hours and observed for the following 14 days. In addition, exposure to higher and lower concentrations of n‐C9 was performed. The concentration of alkane in the brain after exposure exceeded that of blood for the lower alkanes, while the higher alkanes possessed a brain/blood ratio equal to or less than unity. Gross ataxia, general and focal seizure and spasms were observed in animals exposed to n‐C9 in the range from 5280 to 3560 p.p.m. No toxic effects were observed in animals exposed to 2414 p.p.m. of n‐C9 or to the other alkanes. An LC50 value for n‐C9 of 4467±189 p.p.m. was estimated. Despite the clinical improvement in animals surviving the n‐C9 exposure of 4438 p.p.m. (6/10), severe cerebellar damages were found at autopsy at the end of the observation period, with a loss of Purkinje cells as the most prominent feature. Immediatepost mortemexamination (4/ 10) showed marked vascular congestion of the liver as well as slight fatty degeneration but no cerebellar damage. No abnormalities were observed in animals exposed to the other alkanes. The significant distribution in the brain of the n‐C9 alkane, the clinical signs of cerebellar dysfunction and the damage of cerebellar neurons would suggest CNS to be a possible target organ for the toxic effects of

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb01884.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:Hepatic necrosis due to an oral acetaminophen overdose (4.25 g/kg b.wt.) was prevented by pretreatment with disulfiram 100 mg/kg, given for 3 weeks or as a single dose. Twenty‐four hours after acetaminophen the impairment of hepatic function, measured as prothrombin index, and the depletion of hepatic glutathione were prevented. Hepatic cytochrome P‐450 levels were unchanged but cytochrome P‐450 mediated p‐nitroanisole demethylation was reduced by disulfiram pretreatment. Disulfiram pretreatment reduced 24 hour urinary excretion of acetaminophen‐mercapturate and ‐cysteine while excretion of ‐sulfate and ‐glucuronide was unchanged. After 72 hours acetaminophen induced hepatic necrosis were prevented. Identical observations were made in animals pretreated with disulfiram for 3 weeks. Five hours after acetaminophen overdose its irreversible binding to hepatic proteins was not changed. After 24 hours, however, it was increased in animals pretreated with a single disulfiram dose and unchanged in animals pretreated for 3 weeks. The protective mechanism of disulfiram after acetaminophen overdose is not mediated via a change in overall irriversible binding of acetaminophen to

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb01885.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:The β‐adrenoceptor blocker sotalol has been shown to possess class III antiarrhythmic action. The present study was designed to test the hypothesis that class III antiarrhythmic action and positive inotropy may be linked. Since d, 1‐sotalol has previously been reported to have variable inotropic effect, we studied direct effects of the d‐ and 1‐stereoisomer of sotalol on refractoriness and inotropy of isolated rat atria at different strengths of electrical stimulation. Both the d‐ and I‐stereoisomer of sotalol (7.5 × 10‐5M) increased the effective refractory period, and to the same extent. However, d‐sotalol increased isometric contractile force by 10%, while 1‐sotalol had no significant effect, when the atria were stimulated at close to threshold values (10 ± 1 mA). Probably due to release of noradrenaline within the myocardium, contractile force increased when the atria were stimulated at suprathreshold values (40 mA). At suprathreshold stimulation, however, d‐sotalol induced a 10% decrease and 1‐sotalol a 20% decrease, in contractile force. In conclusion, the class III antiarrhythmic action of sotalol is linked with positive inotropy. In the presence of neurotransmitter release, negative inotropic effect of d‐ and in particular 1‐sotalol, may occur due to β

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb01886.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:The enzymatic activity of soluble protein kinase C from mice brain was inhibited by mercuric chloride (II) (HgCl2) and organic mercurials, i.e. methyl mercury, phenyl mercury and p‐chloromercuribenzoic acid (PCMB). The IC50 was 0.08 μM for HgCl2and about 1 μM for organic mercurials. Sulfhydryl blocking reagents such as 5,5′‐dithiobis‐2‐nitrobenzoic acid (DTNB) and N‐ethylmaleimide (NEM) were less potent but nevertheless inhibited the enzymic activity of protein kinase C. The Hill coefficients of HgCl2, DTNB and NEM were close to unity whereas the values for organic mercurials were 1.3 to 1.5. The inhibition was of a non‐competitive type with respect to Hl histone.3H‐PDBu binding activity was also inhibited by all of the reagents in a non‐competitive manner. Mercurials apparently bind to sulfhydryl groups of protein kinase C to inhibit the

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb01887.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:In the present study we investigated the relation between receptor activation and the acinar formation of cyclic nucleotides as a function of time, including effects of calcium. The experiments were performed using collagenase‐isolated rat parotid acini and the cyclic nucleotide content was determined using a specific CAMP binding protein and cGMP antibody. Under physiological conditions, activation of β‐adrenoceptors increased CAMP content 27 fold within 60 sec. This response was not dependent upon the presence of extracellular calcium nor could it be mimicked by the calcium ionophore A23187. The adrenaline‐induced activation of the α‐adrenergic receptors lead to a 19% increase in cGMP content within 15 sec. This response was abolished in the absence of extracellular calcium. Pure activation of the α‐l‐adrenoceptors by phenylephrine resulted in a 62% increase in cGMP content within 15 sec. Finally, carbachol‐induced activation of the cholinoceptors lead to a 50% transient increase in cGMP content within 7 sec. In rile absence of calcium (EGTA present), the basal cGMP level was increased and in addition, the carbachol‐induced cGMP formation was slower in onset and amounted to only 23% within 60 sec. The carbachol‐induced cGMP formation could be mimicked by the calcium ionophore A23187 or by addition of calcium to acini preincubated in a calcium free buffer containing A23187. In conclusion, stimulation‐induced formation of cyclic nucleotides under various conditions proved to be very rapid, well regulated, a

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb01888.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:Oral administration of 0.5 mg/kg/day monocrotophos for 28 days caused death in one out of three animals. A dose of 2.0 mg/kg/day of monocrotophos was 100 percent lethal within 8–1. days after start of insecticide administration. Clinical symptoms were mainly characterised by ataxia, knuckling of limbs, progressive paralysis and prostration. Monocrotophos at both doses caused significant inactivation of erythrocyte cholinesterase (29.4‐50.8%) and caused significant elevation in the serum levels of aspartate and alanine aminotransfera

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb01889.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:Objective and subjective effects on performance of single oral doses of indomethacin (IM) 50 mg and 100 mg and diazepam (DZ) 10–1. mg, alone and in combination, were investigated in two double‐blind studies conducted with parallel groups of healthy drug‐naive student volunteers. Objective and subjective effects were measured at baseline as well as 0.5 and 1.5 hours after treatment. DZ significantly impaired performance in digit symbol substitution, letter cancellation, tracking and flicker fusion tests. It also induced exophoria and caused subjective (visual analogue scales) drowsiness, mental slowness, clumsiness and impaired overall performance. IM proved rather inactive when slightly impairing flicker fusion and digit substitution, and subjectively rendering the subjects clumsier. The combined effects of IM and DZ did not differ from those obtained with DZ alone. Both IM and DZ induced dizziness and their effects in this respect were additive when the drugs were used in combination. It is concluded that single therapeutic doses of indomethacin do not produce major psychomotor effects and do not in this respect increase the effects of diazepam. However, the feeling of dizziness, a side‐effect common to both these drugs, may be additive when the drugs are used in comb

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb01890.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY