摘要:

Abstract:The renal elimination and accumulation of hydroflumethiazide (HFT) during repeated oral administration was investigated in patients with congestive heart failure (CHF). When four doses of HFT were given with 24 hr intervals, the mean 24 hr urinary excretion of HFT was 55–65% of the dose after 75 mg and 53–57% after 150 mg. 24 hr excretion of HFT was not significantly higher after the fourth dose as compared with the first. The renal plasma clearance of HFT was significantly correlated with creatinine clearance (P<0 .01). The biological half‐life (t½β) of HFT ranged from 6.5–27.9 hrs. Mean t½βwas shorter (P<0 .05) after 75 mg (9.2 hrs) than after 150 mg doses (14.1 hrs). The disposition rate constant of HFT was not significantly correlated with creatinine clearance or with renal plasma clearance of HFT, indicating that the volume of distribution was reduced at reduced ren

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01011.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Unilateral radio‐frequency lesions of the parafascicular nucleus were performed in rats. Seven days, but not 24 hrs, postoperatively the following effects were observed in the ipsilateral striatum: (A) an increase in dopamine synthesis as estimated by the accumulation of DOPA following inhibition of cerebral aromaticL‐amino acid decarboxylase; (B) an increase in dopamine levels and (C) a decrease in the number of muscarinic receptors binding sites using [3H] QNB as receptor lig

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01012.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The relationship between renal tubular secretion and saluretic effects of two thiazides (chlorothiazide and hydrochlorothiazide) and clopamide was studied using a modified Sperber technique. The distribution of carbonic anhydrase in the avian kidney was studied by a histochemical method. The modified Sperber technique allows an absolute estimation of the tubular excretion efficiency of a substance, as determined by its True Tubular Excretion Fraction (TTEF). The TTEF values were for chlorothiazide 59%, hydrochlorothiazide 22% and clopamide 10%. Thus, they were all actively secreted by renal tubular cells; most likely through organic anion transport since novobiocin markedly reduced the TTEF values. After infusion of the diuretics into the renal portal system on one side there was only a small ipsilateral excess natriuresis and chloruresis, in spite of their different tubular excretion efficiencies. For hydrochlorothiazide, and especially for chlorothiazide the saluretic effect therefore appears to be largely independent of the tubular fluid concentration of the diuretic and primarily evoked from the peritubular side of the avian nephron. This is in sharp contrast to the primarily luminally induced saluretic effects of furosemide, ethacrynic acid and piretanide. Only chlorothiazide caused an ipsilateral excess excretion of potassium and bicarbonate, probably due to inhibition of carbonic anhydrase since similar effects were seen after acetazolamide. This effect was coupled to tubular secretion of the diuretic, and probably reflects an inhibition of carbonic anhydrase in cortical distal tubules, where the enzyme is present in the apical region of most cells and could be reached by chlorothiazide present in the tubular fluid.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01013.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:In rats pretreated with the dopamine‐β‐hydroxylase (DBH)‐inhibitors FLA‐57 and FLA‐63 (60 mg/kg, intraperitoneally, for 4 and 18 hrs), no effects on the blood acetaldehyde level after ethanol administration or on the activity of the low‐Kmaldehyde dehydrogenase (ALDH) in the liver were found. FLA‐63 but not FLA‐57 decreased the rate of ethanol elimination. FLA‐63 inhibited the low‐Kmenzymein vitro, but much less than the ALDH‐inhibitors disulfiram and cyanamide. FLA‐57 caused no inhibitionin vitro.The results show that the previously observed suppression of ethanol intake in rats by FLA‐57 and FLA‐63 was not caused by an acetaldehyde‐mediated aversion such as during t

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01014.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The distribution of [methyl‐14C]p‐tert.‐butyltoluene was studied in the rat by use of whole‐body autoradiography and liquid scintillation counting. The test substance was administered by inhalation. High concentration of radioactivity was seen in the CNS immediately after inhalation, from where it was rapidly cleared. The liver also contained much radioactivity, as well as the bile, kidneys and the praeputial glands. Increasing amounts of radioactivity were observed in the skin, adipose tissue (brown adipose tissue) and the Harderian gland with increasing survival times. There was still some radioactivity left in the animal 96 hrs after exposure. At least part of the radioactivity in the skin, liver, brown adipose tissue, the Harderian gland and the praeputial glands was found to be non‐extractable from the sections using both polar and non‐pol

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01015.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The effect of daily intraperitoneal administration of Mn2+(4 mg/kg) was investigated on the metabolism of carbohydrates and certain enzymes involved in the oxidation of glucose in the rat liver and blood at the intervals of 30, 60 and 90 days after exposure. Mn2+had no effect on the contents of blood reducing sugars and proteins, however the levels of pyruvic and lactic acids were reduced at 60 and 90 days after the metal treatment. The contents of liver glycogen and proteins remained unaffected while pyruvic acid content was decreased in Mn2+treated rat liver throughout the experimental period. The activities of glycogen phosphorylase and lactate dehydrogenase decreased while that of phosphoglucoisomerase and glucose‐6‐phosphatase increased in the post mitochondrial supernatant at 60 and 90 days of Mn2+exposure. The levels of hexokinase decreased and FDP‐aldolase and fructose‐1, 6‐diphosphatase increased throughout the experimental period. The magnitude of alteration was found to be greater with the increase in the duration of Mn2+treatment. Several of the mitochondrial enzymes in the liver were inhibited in the manganese exposed rats which may be responsible to inhibit the rate of dehydrogenation of Kreb cycle's intermediates alongwith the linked respiratory chain and eventually oxidation in the

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01016.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The oral administration of 500–2500 mg/kg/day dicyclohexyl phthalate (DCHP) to young male Sprague‐Dawley rats for 7 days resulted in liver enlargement and induction of some parameters of hepatic xenobiotic metabolism. Additional studies indicated that the hepatic enzyme induction resembled that of sodium phenobarbitone rather than that of polycyclic hydrocarbons. Morphological examination of the livers of DCHP treated rats revealed centrilobular cell hypertrophy and ultrastructural examination demonstrated marked proliferation of the smooth endoplasmic reticulum. Mitochondrial structure and numbers of peroxisomes (microbodies) were not affected. DCHP treatment did not affect kidney and testes weights but some histological evidence of testicular damage was obtained with 2500 mg/kg/day of DCHP. The metabolites of DCHP, namely monocyclohexyl phthalate (MCHP) and cyclohexanol, also induced certain parameters of hepatic xenobiotic metabolism. MCHP, but not cyclohexanol also produced marked testicular atrophy. It is concluded that DCHP is a weak drug‐type inducer of hepatic xenobiotic metabolism in the rat and the hepatic effects of this phthalate diester are different from those of di‐(2‐ethylhexyl)

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01017.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:N‐demethylation of aminopyrine was demonstrated in the nasal mucosa of C57 B1 mice and Sprague‐Dawley rats by measurements of the14CO2formed at incubation of14C‐aminopyrine with tissue‐slices. The metabolism of aminopyrine by the nasal mucosa was induced by phenobarbital pretreatment and susceptible to inhibition with metyrapone and SKF 525 A suggesting the presence of a cytochrome P‐450‐dependent enzyme system in the tissue. Immediately after injection of14C‐aminopyrine in rats a uniform distribution of radioactivity in the body was recorded. After thirty minutes, however, a preferential localization of radioactivity was found in the nasal mucosa and in the liver. By pretreatment with metyrapone the uptake of radioactivity in the nasal mucosa and in the liver was blocked suggesting that the observed accumulation of radioactivity is due t

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01018.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The influence of histamine on human platelet function was studied by thrombin‐induced serotonin release. The thrombin‐induced3H‐serotonin release was confirmed to be a rapid process which does not require external calcium. Histamine was found to reduce the release of serotonin and the inhibition was abolished when H1‐plus H2‐antagonists were added together with histamine. H1‐ and H2‐receptor stimulation was examined in two ways, by a combination of histamine with cimetidine or diphenhydramine and by the selective agonists 2‐(2‐pyridyl)‐ethylamine and impromidine. In both instances H1‐ and H2‐stimulation was found to reduce the platelet serotonin release. These results suggest a regulatory role of histamine in the platelet function by stimulation of platel

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01019.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Nine healthy male students were exposed for 4 hours at 6‐day intervals to atmospheric concentrations of m‐xylene (8.2 μmol/l; 200 p.p.m.) and 1,1,1‐trichloroethane (TCE) (8.2 and 16.4 μmol/l; 200 and 400 p.p.m.) and also to a combination of 8.2 μmol/l of xylene and of 16.4 μmol/l of TCE. The exposures took place during 6 consecutive weeks. Body sway was recorded with the subjects'eyes closed and open on each day with a strain gauge transducer platform prior to and during the exposures. For the average and for the maximal body sway, the ratio of the sway with the eyes closed to the sway with the eyes open was calculated for each recording. Xylene and TCE at 8.2 μmol/l in air tended to decrease the ratio, whereas the higher TCE concentration alone or in combination with xylene tended to have an opposite effect of the same magnitude. The results support the idea that TCE might exhibit a biphasic pattern of acute effects on the central vestibular system. Pharmacokinetic interactions between xylene and TCE were no

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01020.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY