摘要:

Abstract:Administered to anaesthetized, laparatomized rats bumetanide (10 mg/kg intravenously) evoked a rapid and large diuretic response. This was associated with three to five fold enhancements of urine kallikrein (kininogenase) excretion. In addition bumetanide slightly decreased (approximately 10 mmHg) the blood pressure and temporarily increased renal blood flow (<10%). The capacity of bumetanide to increase urine kallikrein excretion was inhibited either by pretreatment with chlorazanil (3 mg/kg intravenously) or by the infusion of aprotinin (5000 KIE/kg/min.). Kallikrein inhibition did not significantly modify bumetanide induced diuresis, natriuresis, kaliuresis, lowering of blood pressure or renal vasodilating effect.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00914.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Ulcerogenic side‐effects and prostaglandin‐synthesis‐inhibiting capacity are well documented in indomethacin treatment. According to recent works, indomethacin reduces gastrointestinal blood‐flow. Naproxen and paracetamol, claimed to be prostaglandin‐synthesis‐inhibitors, have few ulcerogenic side effects. In an attempt further to study the indomethacin effects and to reveal whether naproxen and paracetamol have similar effects, the labelled microsphere technique was used. The regional blood flow determinations were made before, and 12–15 min. after, the injection of the drugs. Indomethacin 3 mg/kg, reduced gastrointestinal blood flow and increased arterial blood flow to the liver. Naproxen, 10 mg/kg, and paracetamol, 25 mg/kg, had no effects except for a very small decrease in liver blood flow with paracetamol. The results strongly suggest that, at least under light general anaesthesia, prostaglandins influence resting blood flow in the gastrointestinal tract, the liver and parts of the brain. The results more raise doubts whether naproxen and paracetamol inhibit prostaglandin synthesis in these tissues. These data offer a plausible explanation as to why naproxen and paracetamol are usually well tolerated in the gastrointestinal tract. None of the drugs tested influenced resting blood flow in muscles, tendons, bones, joints or synov

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00915.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The effect of adenosine and adenine nucleotides on sympathetic neuroeffector transmission in the rabbit isolated pulmonary artery and aorta was studied. Adenosine (10−5— 3 × 10−4M) decreased the contractile response of pulmonary artery and aorta evoked by electrical‐field stimulation. The decrease was reversible. No tachyphylaxis developed. Inhibition of either adenosine deaminase by deoxycoformycin (3.6 × 10−6M) or of adenosine transport by dilazep (3 × 10−6M) did not alter the inhibitory effect of adenosine on the neurogenic contractions in the pulmonary artery. However, deoxycoformycin plus dilazep markedly enhanced the inhibitory effect of adenosine. The calcium antagonists nifedipine (1.5 × 10−8M) and nimodipine (1.3 × 10−8M) had no effect on the adenosine‐induced inhibition. This was also the case with theophylline (5 × 10−5M), atropine (10−7M), and the prostaglandin synthetase inhibitors indomethacin (5 × 10−5M) and suprofen (3 × 10−5M). The contractile response of the pulmonary artery elicited by exogenous (—)‐noradrenaline (NA; 10−9— 3 × 10−4M) was essentially not altered by adenosine (10−5— 3 × 10−4M). Adenosine (10−4M) did not alter the spontaneous3H‐outflow from rabbit aorta preloaded with3H‐(—)‐noradrenaline (3H‐NA). Adenosine (10−5— 3 × 10−4M), ADP (10−4M), ATP (10−5M), and inosine (10−4M) diminished the overflow of tritium from pulmonary artery and aorta preloaded with3H‐NA. The spontaneous outflow of tritium from aorta preloaded with3H‐NA consisted of3H‐NA (17%),3H‐dihydroxyphenylglycol (3H‐DOPEG; 30%),3H‐dihydroxy‐mandelic acid (3H‐DOMA, 4%),3H‐O‐methylated and deaminated metabolites (3H‐OMDA; 42%), and3H‐normethanephrine (3H‐NMN; 2%). Adenosine (10−5and 10−4M) enhanced3H‐DOPEG and3H‐NMN, decreased3H‐NA, and did not alter3H‐DOMA and3H‐OMDA. The stimulation‐evoked overflow of tritium for aorta preloaded with3H‐NA consisted of3H‐NA (31%),3H‐DOPEG (18%),3H‐DOMA (2%),3H‐OMDA (46%), and3H‐NMN (3%). Adenosine (10−5and 10−4M) enhanced3H‐NA and3H‐DOPEG, decreased3H‐OMDA and did not alter3H‐DOMA and3H‐NMN. Adenosine (10−6— 10−4M) did not alter the accumulation of3H‐NA (10−8M) by aorta.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00916.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The site and mechanism of action of McN‐A‐343 (4‐m‐chlorophenylcarbamoyloxy)‐2‐butynyltrime‐thylammonium chloride) on sympathetic neuroeffector transmission in the rabbit isolated pulmonary artery was studied. Low concentrations (10−6— 3 × 10−5M) of McN‐A‐343 and cocaine enhanced (up to 210 and 236%, respectively) the contractions evoked by electrical‐field stimulation, while higher concentrations (10−4— 3 × 10−4M) inhibited them. McN‐A‐343 (10−4M) caused an initial transitory potentiation (222% of control) of the stimulation‐evoked contractions followed by an inhibition. In the presence of cocaine (3 × 10−5M), the potentiation caused by McN‐A‐343 was prolonged and the secondary inhibitory phase was thus abolished. Physostigmine (10−5— 10−4M), hexamethonium (10−5M), atropine (3 × 10−7M), suprofen (10−5M), and 4‐aminopyridine did not alter the effect of McN‐A‐343 (10−4M). Cocaine (3 × 10−5M)and(+)‐amphetamine (10−5M) reversed the McN‐A‐343‐evoked block, while they did not alter the inhibition caused by tetracaine (3.2 × 10−5M). Atropine (3 × 10−7M) had no effect on the McN‐A‐343‐induced block, while 4‐aminopyridine (10−4M) caused a partial and transitory reversal. On the aorta McN‐A‐343 (10−4M) did not alter the contractile concentration‐response curve of (—)‐noradrenaline (10−9— 3 × 10−4M), while that of serotonin (10−8— 3 × 10−5M) was moved to the right in a competitive manner. McN‐A‐343 (10−4M) did not alter the contractions evoked by noradrenaline (10−7M) during the period corresponding to the stimulation‐evoked enhancement and subsequent inhibition. McN‐A‐343 (10−4M) slightly antagonized the contractions caused by tyramine (10−6— 10−3M) and carbachol (10−6— 10−3M). It is concluded that McN‐A‐343 enhances stimulation‐evoked transmitter release by a presynaptic facilitatory action mediated via receptors localized on the outer surface of adrenergic neurones and to a lesser extent by inhibition of noradrenaline re‐uptake. The enhancement does not involve presynaptic nicotine or muscarine receptors. Furthermore, McN‐A‐343 inhibits transmitter release by acting as an adr

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00917.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:D‐penicillamine (D‐pen) in doses of 20, 100 and 500 mg/kg/day or D‐pen 100 mg/kg/day plus methylprednisolone (MP) 2.0 mg/kg/day was administered daily for 42 days to rats implanted with viscose‐cellulose sponges. Operated, pairfed rats served as controls. D‐pen increased the DNA content of granulation tissue, but had no effect on the amount of tissue produced. In contrast, high dose D‐pen reduced the content of DNA and collagen in skin. A dose related inhibition of collagen crosslink formation occurred in all tissues, particularly in skin, as indicated by increased proportions of extractable collagen with increased α/β chain ratio and aldehyde content. Moreover, low doses of D‐pen increased the hydroxyproline/proline ratio of acid soluble skin collagen, presumably due to solubilization of type III collagen as demonstrated by SDS‐polyacrylamide gel electrophoresis in the presence of 3.6 M urea. These changes were associated with increased skin fragility and edema plus excess elastin deposition in the aorta after high dose D‐pen treatment. Low dose D‐pen stimulated the35S‐sulphate uptake into the sulphated glycosaminoglycans (GAGs) of granulation tissue without altering their relative amounts, whereas high dose D‐pen reduced the concentration of chondroitin‐4/6‐sulphate in skin. MP antagonized the solubilizing effect of D‐pen on collagen, probably by inhibition of the collagen synthesis. In addition, MP inhibited the cell proliferation and GAG metabolism. Food restriction reduced the DNA content of granulation tissue. The inhibitory effect of D‐pen on the formation of granuloma collagen crosslinks in the presence of unaltered rate of collagen biosynthesis may diminish the amount of fibrotic tissue due to increased degradability of crosslink deficient collagen. Simultaneous administration of MP may facilitate this effect by inhibiting the biosynthesis of collagen. However, long‐term D‐pen treatment seems to increase the susceptibility o

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00918.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Cadmium chloride cleared rapidly from the lungs and translocated mainly into the liver within 24 hrs of an intratracheal instillation. Further pulmonary clearance and hepatic accumulation were very slow during the remaining observation period of 24 days. Though, the uptake of cadmium by kidneys was lower but the level increased consistently with the time after instillation. The induction of metallothionein synthesis by cadmium might be responsible for accumulation and retention of cadmium in liver and kidneys significantly.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00919.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The levels of the persistent organochlorine compounds HCB, sum‐DDT (1.1 DDE+1.1 DDD+DDT), DDE and PCBs were determined in 133 Norwegian human milk samples from 7 cities with various degrees of industrialization. All samples contained organochlorines. No dramatic geographical differences were observed. The average HCB, sum‐DDT, DDE and PCB levels in human milk were 2.1±1.0, 29.8±23.5, 25.8±20.3 and 23.9±13.7 p.p.b. respectively (126±128, 1440±950, 1270±850 and 1210±690 p.p.b. respectively in human milk fat) which are among the lowest reported. The present results were compared to Norwegian results from 1970 and 1976. A slight decrease in the average HCB levels was observed from 1976–1979. The average PCB levels which doubled from 1970–1976 showed no or only a slight increase from 1976–1979. The distinct decrease in average sum‐DDT levels observed from 1970–1976 continued during the period 1976–1979. The present survey demonstrated that human milk is a good indicator substance in monitoring the environment for contamination by organochlorine compounds. The results were evaluated toxicologically by comparison with maximum residue limits and acceptable daily intakes (FAO/WHO 1978). It was concluded that the present levels of organochlorines in Norwegian human milk did not represent any threat

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00920.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:A universal gas chromatographic method for the determination of the most commonly used antidepressant drugs in I ml of serum is described. Prior to extraction the samples were washed with hexane at acid pH. After the hexane wash the drugs were extracted into hexane at pH approximately 10, and subsequently reextracted from the hexane into a 1% solution of formic acid in methanol. The methanolic phase was evaporated, the residue dissolved in isopropanol and analysed by gas chromatography with nitrogen detection on a 3% OV‐225 column. Recoveries for amitriptyline, nortriptyline, clomipramine, desmethylclomipramine, doxepin, desmethyldoxepin, imipramine, desipramine, maprotiline, protriptyline, trimipramine and desmethyl‐trimipramine were found to be 80% or higher. Limits of detection were found to be 5–10 ng/ml for tertiary amines and 10–20 ng/ml for secondary amines. Interferences from some common basic drugs were investigated as well as interferences between different antidepressant drugs. Gas chromatographic data are given for 28 drugs and meta

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00921.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The effect of hydroflumethiazide (HFT) on renal excretion of sodium, chloride, and potassium was studied in congestive heart failure and related to urinary excretion of thiazide and aldosterone. HFT 75 or 150 mg was administered orally once daily for 4 days to 8 male patients with roentgenological evidence of enlarged heart and slight or no peripheral oedema receiving digitalis and controlled diet. Urinary excretion of HFT did not change after repeated doses, whereas urinary excretion of a metabolite increased significantly. Initially, HFT induced a significant increase in the urinary excretion of sodium and potassium. After repeated doses, the natriuretic effect declined gradually in 6 of the patients. There was consistently a small natriuretic effect and a large kaliuretic effect at high serum aldosterone concentrations and high urine aldosterone excretion rates, whereas at low aldosterone levels, there was a wide range in magnitude of these effects. Relationships of the log urinary excretion rate of HFT to the increase in urinary excretion rate of sodium, chloride, and potassium showed positive and significant correlations. It was concluded that reduced natriuretic effect of HFT in congestive heart failure is not due to reduced delivery of thiazide to renal tubular cells but to compensatory adjustments of the kidney in part induced by aldosterone.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00922.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Effect of acute and chronic exposure to and withdrawal from ethanol on3H‐muscimol binding in the forebrains and cerebelli and on withdrawal behaviour was investigated in 30 rats. Chronic exposure to and withdrawal from ethanol produced a significant reduction in the number of muscimol binding sites in the cerebelli. A negative correlation was observed between the number of muscimol binding sites in the forebrain and cerebellum in the chronic ethanol and withdrawal groups. Relatively high correlations were found between the number of muscimol binding sites and audiogenic seizure scores during withdrawal from ethanol. Since impaired GABAergic function is associated with increased susceptibility to seizures, there may be a causal relationship between the observed changes in muscimol binding and ethanol‐induced audiogenic withdrawal seizu

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00923.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY