摘要:

The metabolism of vinylidene chloride (VDC) and carbon tetrachloride (CCl4) was investigated by measuring the removal of the compounds from the atmosphere of a closed exposure system occupied with male rats. Hepatotoxicity was evidenced in the same rats by determining serum enzyme activities of the aminotransferases (GOT, GPT) and sorbitol dehydrogenase (SDH) before, at the end of the exposure time and 24 hrs later. Control rats exposed to VDC concentrations up to 2000 p.p.m. showed only slight increases of serum aminotransferase‐ and SDH‐activities, which were not at all observed under hypoxic conditions. Hypoxia evoked a small, but significant reduction of the VDC metabolism at 500 p.p.m., but not at 2000 p.p.m. exposure concentration. In contrast to VDC CCl4‐metabolism (150 p.p.m.) was increased under hypoxia and consequently hepatotoxicity was aggra

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01257.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The acute behavioural consequences of intragastric p,p′‐DDT in high doses to mice are stimulus sensitive abrupt muscle jerks (myoclonus). The serotonin (5‐HT) precursor 5‐hydroxytryptophan (5‐HTP) ameliorated in contrast to the natural precursor tryptophan, the neurotoxin‐induced myoclonus. The extracerebral decarboxylase inhibitor carbidopa and the selective 5‐HT reuptake inhibitor paroxetine both enhanced the antimyoclonic action of 5‐HTP. The effect was reversed by the 5‐HT receptor blockers cinanserine and methysergide. The data add further evidence to a central serotonergic mechanism involved in p,p′‐

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01258.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

In male Charles Foster rats, intracerebroventricular clonidine (0.2, 1.0, 10 mmol/l) caused dose dependent increase in the urine output and sodium excretion (P<0.01). Urinary creatinine excretion was decreased to a significant level (P<0.02). Urinary potassium excretion was increased but was not dose dependent. Maximal increase in the urine volume occured during first hour of clonidine administration. Intraperitoneal administration of clonidine in similar molar concentration failed to produce changes in the urine volume. The results indicate that clonidine‐induced diuresis is centrogenic and is attributed to the inhibition of the release of vasopressin from central hypothalamoneurohypophyseal axi

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01259.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Haloperidol, a butyrophenone neuroleptic, is metabolically reduced in man, but not in rat and not in many other experimental animals. Here we present data that describes reductive haloperidol metabolism in guinea pigsin vivo.When haloperidol was injected intraperitoneally to guinea pigs, it was converted to reduced haloperidol so quickly that 1 hr after the injection the concentration of haloperidol was only about one fifth of that of reduced haloperidol. Dopamine metabolism was enhanced in the striatum after the administration of reduced haloperidol, but this enhancement could mostly be explained by oxidation of a small amount of reduced haloperidol back to haloperidol. The molecular mechanisms of haloperidol reduction should be further studied using guinea pigs as a model for human haloperidol metabolism.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01260.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Myocardial pharmacokinetics and dynamic effects of the non‐steroidal antiinflammatory drug ibuprofen were studied in isolated, spontaneously beating and retrogradely perfused rabbit hearts. Both myocardial uptake and disposition of ibuprofen showed two‐compartment characteristics, which possibly reflects extracellular and intracellular binding sites. Initial and terminal kinetic half‐lives were about 0.6 and 13.4 min., respectively. Vdβwas about 82 ml/g myocardial tissue. Stepwise increased ibuprofen concentrations from 30 to 160 μg/ml in the Krebs‐Henseleit perfusion liquid produced a progressive increase in coronary flowrate up to 178%, which then decreased somewhat at higher concentrations. Preliminary observations showed a direct relaxing effect on PGF‐2α produced contractions in coronary vasculature. Oxygen consumption increased simultaneously to 143% at 160 μg/ml and then decreased. Myocardial contractility (measured by amplitude and rate of contraction) decreased progressively to about 55% at concentrations from 60–160 μg/ml and further to 20% at 580 μg/ml. Myocardial efficiency expressed as the ratio of contraction rate to oxygen consumption decreased to about 0.2. Heart beat frequency decreased simultaneously to 73%. The electrocardiographic PQ and QRS intervals increased to 143 and 139%, respectively, whereas the QT interval did not increase significantly. Asystolia occurred in some cases at ibuprofen concentrations of 580 μg/ml. The findings suggest that ibuprofen at therapeutic concentrations may possibly produce some coronary vasodilation accompanied by a slight negative inotropic effect. Interactions with other cardioactive drugs seem possible. The drug may cause direct cardiotoxic effects at supratherapeu

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01261.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The binding sites labelled by3H‐dihydromorphine,3H‐ethylketocyclazocine and3H‐D‐Ala2‐L‐Leu5‐enkephalin in mouse brain membranes were characterized in cross‐competition studies. The data was evaluated by simultaneous non‐linear least‐squares regression analysis with the “Ligand” program (Munson&Rodbard 1980), that had to be upgraded to handle more than three binding sites. By statistical analysis four different binding sites were identified. Three of the sites probably correspond to the pharmacologically well characterized μ, ∂ and δ‐opioid receptors, respectively, and their binding capacities relate as 1:1.5:2.5. Classification of the fourth site is more problematic. Using3H‐ethylketocyclazocine it had higher capacity than the others and bound ethylketocyclazocine with a relatively high affinity (Kd= 10 nM), dihydromorphine with a very low affinity (Kd>10−5M) and showed no binding of D‐Ala2‐L‐Leu5‐enkephalin. In displacement studies, N‐allylnorcyclazocine (SKF 10,047), though unselective, bound with highest affinity to the μ and the fourth site. Since naloxone did not bind to this fourth site, it can not be termed an opioid site in a strict sense, but it might have some relevance in view of non‐naloxon

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01262.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The influences of different calcium‐entry blockers, sialidase and caffeine on the biphasic contraction induced by prostaglandin (PG) F2αin the feline basilar artery (BA) were studied in calcium‐free medium. After incubation in calcium‐free solution, PGF2αinduced a contraction of the BA amounting to 87% of the contraction in calcium‐containing solution. The response was biphasic in 41 out of 42 vessel segments. PGF2α‐induced contractions were markedly attenuated in TRIS‐buffered solutions as compared to contractions in Krebs solution. PGF2αfailed to induce a biphasic contraction (8 out of 9 preparations) in calcium‐free HEPES‐buffered solution. Calcium entry blockade with 1 mM manganese or 10−5M diltiazem abolished the second and major phase of the PGF2α‐induced contraction in calcium‐free Krebs solution. The second contraction phase was also eliminated in four out of five preparations pretreated with sialidase (1 unit/ml for 30 min.), but was unaffected by a brief exposure to 20 mM caffeine in calcium‐free medium. The present findings strongly support previous suggestions that a major part of the PGF2α‐induced contraction in calcium‐free medium is mediated via the release of calcium bound to the ext

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01263.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The effect of day light and ultraviolet radiation (360 nm) on mechanical responses to BAY K 8644 (methyl‐1,4‐dihydro‐2,6‐dimethyl‐3‐nitro‐4‐(‐2‐trifluoromethylphenyl)‐pyridine‐5‐carboxylate), potassium (K+) and noradrenaline (NA) of rat aorta rings was investigated. The contractile response to BAY K 8644 (10−6M) obtained before and after exposure of the BAY K 8644 stock solution to ultraviolet radiation was unchanged and equal to that of K+, 125 mM. Ultraviolet radiation and day light did not affect responses evoked by K+(125 mM) and NA (1.8 × l0−5M). In contrast to this both types of light relaxed vessels contracted by BAY K 8644 (10−6M). The light induced relaxations were reversible, unaffected by addition of propranolol (3 × 10−6M) and could not be eliminated by washing the preparations repeatedly with Krebs solution. In vessels contracted by K+(125 mM) and NA (1.8 × 10−5M) ultraviolet radiation induced a reversible relaxation in the presence of BAY K 8644. BAY K 8644 (10−4M) and nifedipine (10−8M) relaxed preparations contracted by K+. Nifedipine (10−6M) totally relaxed preparations contracted by BAY K 8644 (10−6M). Ultraviolet radiation eliminated the relaxant effect of nifedipine and decreased the relaxant effect of BAY K. 8644 (10−4M). The results indicate that BAY K 8644 is more light‐stable than nifedipine and that BAY K 8644 sensitized the vascular smooth muscle to ultraviolet radiation as well as day light. Consequently this shoul

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01264.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The changes in the activity of some enzymes in parenchymal liver cells were measured in the perfusate of rat isolated liver after a single envenomation with two different doses of Hornet's (Vespa orientalis) venom sac extract (VSE). The maximal observed enzymatic changes were significant: twenty four fold rise of alkaline phosphatase E.C.3.1.3.1(ALP), six fold rise of alanine aminotransferase E.C.2.6.1.2. (ALT) and nine fold rise of aspartate aminotransferase E.C.2.6.1.1. (AST) activity. There were moderate changes (four fold) in lactic dehydrogenase activity E.C.1.1.1.2.7. (LDH) and a non‐significant change in γ‐glutamyl‐transferase E.C.2.3.2.1. (GGT) activity. These changes varied with the venom's dose. Also a decrease in the rate of effluent draining outviathe hepatic vein was noted as an additional sign of liver damage. In light of the biochemical evidence presented here, as well as in previous work, it seems that no further biochemical proof is needed to establish the hepatotoxicity of VSE in rats, cats and probably humans too. It seems that VSE is a predictable hepatotoxin causing a pattern of enzyme changes of the cholangiocellula

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01265.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The effects of 8‐bromo cyclic GMP (1 × 10−5M) on the levels of lactate, NAD+, NADH, AMP, ADP, ATP, creatine phosphate (CrP) and creatine were studied in the ischaemic Langendorff‐perfused rat heart. The NAD+/NADH ratio and the energy charge were also calculated. The dependence of the effect of 8‐bromo‐cGMP on substrate availability was also studied by adding pyruvate (5 mM and 10 mM) to the perfusate, and by comparing the changes to those during perfusion with glucose alone. When glucose (11 mM) was used as the only substrate, 8‐bromo‐cGMP administration resulted during ischaemia, in a decrease of the NADH level, and in an increase of the energy charge. When pyruvate (5 mM) was added to the perfusate, 8‐bromo‐cGMP administration resulted in an increase in the NAD+/NADH ratio and in an increase of the energy charge. When the pyruvate concentration was further increased (10 mM), no changes were seen in the beforementioned variables after 8‐bromo‐cGMP administration. It is concluded that the effects of 8‐bromo‐cGMP may be exerted by an enhancement

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01266.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY