ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01517.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:The pharmacokinetics of cefotaxime and its main metabolite des‐acetyl‐cefotaxime were studied after a single 1000 mg intravenous dose in 8 patients with end stage renal disease during peritoneal dialysis. Pharmacokinetic parameters were determined by iterative non‐linear least squares regression analysis of plasma and dialysis fluid drug concentration curves. Biological half‐life of cefotaxime ranged from 2.3 to 8.2 hours and total plasma clearance from 11 to 103 ml/min. (0.11 to 1.7 ml/min./kg b.wt). Only 1.4% to 4.2% of the intravenous dose of cefotaxime was distributed to the dialysis fluid. We conclude that the dosage of cefotaxime to uraemic patients adjusted to the renal function needs no further adjustment during peritoneal d

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01518.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Chloral hydrate (CH), an intermediate metabolite of trichloroethylene, is reduced to trichloroethanol (TCE) by alcohol dehydrogenase and aldehyde reductase, and is also oxidized to trichloroacetic acid (TCA) by the nicotinamide adenine dinucleotide (NAD)‐dependent enzyme, CH dehydrogenase. Alcohol dehydrogenase requires reduced NAD (NADH), aldehyde reductase requires reduced nicotinamide adenine dinucleotide phosphate (NADPH) and CH dehydrogenase requires NAD to complete the reaction. It is unclear which reaction is predominant at the physiological redox level in intact liver cells. To study this question, we perfused the livers of well‐fed rats with Krebs‐Ringer buffer solution containing 0.1 mM pyruvate/1.0 mM lactate. The levels of TCE and TCA in the effluent were measured by gas chromatography, and the fluorescence of reduced pyridine nucleotides was measured with a surface fluorometer. When a low concentration (below 0.25 mM) of CH was administered, more TCA than TCE was produced. When a high concentration of CH was administered (over 0.5 mM), TCE production was greater. Reduced pyridine nucleotides decreased inversely with the CH concentration. Even at low CH concentrations, pyridine nucleotides were not reduced. When 10 mM lactate was added to the perfusate in order to reduce the pyridine nucleotides in the liver cells, the TCE/TCA ratio increased. On the other hand, the TCE/TCA ratio tended to fall following the addition of 5.0 mM pyruvate. In conclusion, the TCE/TCA ratio was altered according to the concentration of CH, and to the redox level of pyridine nucleotides in the

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01519.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:The pressor effects of a single infusion of calcium gluconate (1375 mg) were measured in 20 patients, aged 31‐63 years, with mild and moderate essential hypertension, being on long‐term treatment with the slow calcium channel blocker verapamil. The calcium load induced a signifiant (P<0.001) increase in mean serum ionized calcium (from 1.240.01 to 1.40±0.2 mmol/1). This did not alter mean blood pressure or mean heart rate, although the individual patients responded differently to the mild hypercalcaemia; a significant fall in blood pressure being observed in a few patients. These results demonstrate the unpredictable effects of an increase in extracellular calcium on vascular smooth muscle cells and suggest that an intravenous bolus of 1375 mg calcium gluconate is not effective in counteracting the hypotensive action of verap

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01520.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:The effect of chlorpromazine on the metabolism of3H‐noradrenaline (3H‐NA) released spontaneously or by electrical‐field stimulation was studied on the rabbit isolated aorta preloaded with3H‐NA. Chlorpromazine (10−6M) neither altered the spontaneous outflow of total tritium nor had any major effect on the distribution of the3H‐outflow on3H‐NA and its3H‐metabolites. Chlorpromazine (10−6M) altered the distribution in stimulation‐evoked3H‐overflow. Thus,3H‐NA and3H‐NMN were increased,3H‐DOPEG was markedly decreased and3H‐DOMA and3H‐OMDA were unchanged. It is concluded that chlorpromaz

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01521.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Twenty patients with lung cancer, treated with cisplatin and etoposide, were divided into two groups at random and given antiemetic therapy consisting of either high‐dose metoclopramide (MCL) intravenously (8 mg/kg over 7 hours) and chlorpromazine (CPZ) (50 mg orally), or a reduced dose of MCL (6 mg/kg over 7 hours) and CPZ (50 mg orally). Serum MCL concentrations were monitored during the infusions. In the two groups, 33% and 38% vomited during and after the courses, and antiemetic control was achieved in 83% and 75% of the patients. There was no significant difference between the groups, and side effects were negligible. MCL concentrations exceeded 0.7 μg/ml in all patients, with great inter‐individual varia

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01522.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Rats metabolized a sublethal gastric dose (0.73 mmol/kg) of allyl alcohol (AlOH) within 10‐15 min. Oxidation of AlOH to acrolein was accompanied by an equally rapid, but only transient depletion of hepatic reduced glutathione (GSH). GSH was restored to levels above normal within 5 hrs. Simultaneously, AlOH provoked marked elevation of alanine aminotransferase, γ‐glutamyl transpeptidase, and glutamate dehydrogenase activities in plasma and formation of lesions mainly in the periportal regions of the liver. Inhibition of alcohol dehydrogenase by 4‐methyl pyrazole completely counteracted these effects. On the other hand, attempts to potentiate the toxicity of acrolein by the aldehyde dehydrogenase inhibitor cyanamide enhanced only the release of alanine aminotransferase. Co‐administration of ethanol (3 g/kg) inhibited the rate of AlOH oxidation by more than 90%. Although with ethanol GSH remained depleted for several hours, the release of enzymes was markedly suppressed and the histologic changes completely prevented. These results indicate that the rapid rate of acrolein formation, rather than persistently lowered GSH content, is crucial in the hepatotoxicity of AlOH. They also suggest, that oxidation of acrolein via aldehyde dehydrogenase does not represent a major pathway for its detoxicatio

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01523.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Kidney cells were isolated from rats pretreated by daily subcutaneous doses of cadmium metallothionein (CdMT; 0.05‐0.2 mg Cd/kg x 5) and from non‐pretreated rats. Upon exposure to CdCl2in vitro(0‐200 μg Cd/ml), a concentration dependent decrease in viability was observed in the non‐pretreated cells, while no such decrease occurred in the pretreated cells indicating that these cells were more resistant to the toxic action of cadmium. There was a higherin vitrouptake of Cd+2and an increased metallothionein (MT) concentration in the pretreated cells (compared to nonpretrated cells). Subcellular distribution studies revealed that Cd was mainly recovered in the “cytosol” fraction. The higher total cadmium uptake in pretreated cells corresponded to an increase of Cd in “cytosol” and “nuclear” fractions. This observation may be explained by MT‐binding of Cd in the cells and is in accordance with a possible protective effect of induced MT in the pretreated cells. In order to assess whether pretreatment‐induced tolerance to cadmium toxicity – indicated by the cellular studies – could also be observedin vivo, some whole animal experiments were also performed. A dose‐related proteinuria was observed in non‐pretreated rats after a single subcutaneous administration of 109Cd‐MT at doses of 0.05 and 0.4 mg Cd/kg. Urinary total Cd,109Cd and MT was also increased in a dose‐related fashion. Cadmium concentrations in kidney were dose related and reached 19 μg/g wet weight. In contrast, in animals repeatedly pretreated with CdMT according to 1), no proteinuria was observed after administration of the same single doses of109CdMT Total Cd,109Cd and particularly MT‐concentrations in urine were lower in such pretreated animals than in non‐pretreated ones in spite of the accumulation of higher tissue concentrations of total Cd (up to 80 μg/g). The pretreatment was thus shown to prevent some of the acute nephrotoxicity of CdMT, poss

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01524.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Raclopride, a new potential antipsychotic agent blocking central dopamine (D2) receptors, was found to suppress exploratory locomotor activity, treadmill locomotion and conditioned avoidance response in rats. The threshold dose for effects in these test situations was about 0.5 mg/kg intraperitoneally. A considerably higher dose, 16 mg/kg intraperitoneally, was needed to produce maximal catalepsy. Maximal effects were obtained within 1–2 hrs and the duration of the effect was 2–8 hrs, depending on the test situation. The behavioural profile of raclopride is different from the classic antipsychotic haloperidol, blocking central dopamine (DA) receptors, as well as from the partial DA agonist preclamol, which inhibits central DA neurotransmission by activating DA autoreceptors. Thus, although similar to haloperidol in other respects, comparatively high doses of raclopride are needed to produce catalepsy, indicating less propensity to produce severe extrapyramidal side effects. Raclopride and preclamol are about equipotent in suppressing exploratory locomotor activity. However, raclopride is more potent than preclamol in suppressing treadmill locomotion, conditioned avoidance behaviour and catale

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01525.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Intraperitoneal administration of cadmium acetate (Cd2+, 0.4 mg/kg) to rats daily for 30 days was found to inhibit the activity of superoxide dismutase (SOD), to increase the endogenous levels of lipid peroxides and lipid peroxidation in the liver and the kidney tissues. Addition of varying concentrations of Cd2+(10‐100 μM)in vitroalso inhibited SOD in both the tissues. It appears that the inhibition of SOD could be due to direct interaction of Cd2+with the enzyme molecule. Lipid peroxidation reaction was also increased after addition of Cd2+to fresh homogenate of these tissues, however, it did not produce any effect in heated homogenates inin vitroexperiments. It indicated that Cd‐induced elevation in lipid peroxidation may not be only due to the possibility of higher level of superoxide radicals resulting from inhibited superoxide dismutase but could also be as a result of direct action of Cd2+on the peroxidation reaction. Thus, the possibility of involvement of free radical damage to the membrane structures in Cd toxicity has been demonstrated in these experim

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01526.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY