摘要:

Abstract:Frequently reported adverse inflammatory skin and airway reactions have been reported in subjects being medicated with angiotensin converting enzyme (ACE)‐inhibitors. Intradermally evoked wheal and flare reactions to ovalbumin, capsaicin and bradykinin, in ovalbumin sensitized guinea pigs, was previously demonstrated to be enhanced by pretreatment with the ACE‐inhibitor MK 422 (the active parent diacid of enalapril).In vitroresults from this study demonstrate that the ACE‐inhibitor MK 422 degranulated guinea pig lung and skin mast cells as well as human basophils, and enhanced allergen‐evoked histamine release. Local capsaicin pretreatmentin vivoof guinea pig skin decreased spontaneous and allergen‐triggered release of histaminein vitrofrom skin mast cells. No clear enhancing effect of MK 422 was seen on the allergen‐triggered histamine releasein vitrofrom capsaicin pretreated skin, and the spontaneous release was unaffected by the ACE‐inhibitor. The allergen‐triggered wheal and flare reaction in ovalbumin sensitized guinea pigs was potentiated by MK 422 and the late phase reaction of the inflammatory response was especially augmented. Capsaicin pretreatment of the guinea pigs abolished this late phase reaction as well as the inflammatory enhancing effect of MK 422. Ourin vitroresults from capsaicin pretreated skin indicate that the reduced inflammatory responsein vivoin capsaicin pretreated skin is due not only to capsaicin induced depletion of neuropeptides from sensory nerves, but also to secondary degranulation of mast cells by one or more of

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00622.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The effect of different serotonin (5‐HT) agonists and antagonists on the discriminative stimulus properties (cue) induced by 8‐hydroxy‐2‐(di‐n‐propylamino)‐tetralin (8‐OHDPAT), 1‐(m‐trifluoromethylphenyl)piperazine (TFMPP) and d‐LSD (d‐lysergic acid diethylamide) has been investigated. The 8‐OHDPAT cue was mimicked by the 5‐HT1Aagonists ipsapirone, buspirone, gepirone and partially by 5‐methoxy‐N,N‐dimethyltryptamine and d‐LSD. 5‐HT1B(TFMPP and RU 24969) and 5‐HT2agonists (DOM, DOI and quipazine) were ineffective and induced disruption of responding. The 8‐OHDPAT cue was antagonized by spiroxatrine and partially by (‐)‐alprenolol, whereas selective antagonists of 5‐HT2(ketanserin and ritanserin), 5‐HT3(ICS 205–930), α1‐adrenergic (prazosin) and β‐adrenergic receptors (ICI 118.551) were ineffective. The TFMPP cue was mimicked by RU 24969 and partially by quipazine. Other compounds were ineffective. Only (‐)‐alprenolol antagonized the effect of TFMPP. The d‐LSD cue was mimicked by DOM, DOI, quipazine, 5‐methoxy‐N,N‐dimethyltryptamine and partially by ipsapirone, TFMPP and RU 24969. The 3 latter compounds and 5‐HT1Aagonists induced disruption of responding. The d‐LSD cue was antagonized by ketanserin and ritanserin, but not by the other antagonists mentioned above. The specific inhibitor of 5‐HT uptake citalopram was not able to substitute for any of the 3 agonists. It is concluded that the drug discrimination technique can be used to identify selective agonists and antagonists of 5‐HT receptor subtypes. Compounds with mixed effects on 5‐HT receptor subtypes can also be identified. These show add

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00623.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:Mevinolin, a competitive inhibitor of 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase activity, is a potent inhibitor of cholesterol synthesis. We have tested the effects of mevinolin on cell replication (3H‐thymidine incorporation), prostacyclin production (6‐keto‐PGF1α) and cell death (51Cr release) in cell cultures (human umbilical vein endothelial cells, bovine endothelial cells, human fibroblasts and bovine smooth muscle cells). Mevinolin concentrations ranging from 0.05 μmol/l (reported therapeutic concentration) to 20 μmol/l were used. In human endothelial cells the replication was reduced by 11% at a concentration of 2.0 μmol/l (P<0.01). In fibroblasts and smooth muscle cells the reduction was significant already at 0.1 μmol/l (10%, P<0.01). The prostacyclin production was reduced in endothelial cells at 1.0 μmol/l (19%, P<0.01) and in smooth muscle cells at 2.0 μmol/l (15%, P<0.05). At 20 μmol/l both cell replication and prostacyclin production was markedly reduced by about 40% in all cell types. No effects on51Cr release or trypan blue staining was seen at any concentration. It is concluded that mevinolin has an effect on DNA synthesis and prostacyclin production on the tested cell typesin vitro.These effects were, however, observed only at concentrations higher than those recommended

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00624.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:Sprague‐Dawley rats were used to evaluate a model system for studying the hepatotoxicity caused by microcystin‐LR (MCYST‐LR), a toxin produced by the cyanobacterium (blue‐green alga)Microcystis aeruginosa, and for evaluating thein vivotherapeutic potential of cholestyramine resin (CTR) which was found to bind the toxinin vitro.Female rats were treated with either toxin or an equivalent volume of the saline vehicle by direct administration into the lumen of anin situisolated ileal loop. Male rats were dosed with toxin as described above, and then animals were dosed in the ileal loop with either cholestyramine resin (CTR, 50 mg/rat) or an equivalent vehicle. The survivors in both studies were killed six hours after dosing and hepatotoxicity was assessed by change in relative liver weights. In all groups given toxin alone, there was a significant increase in liver weight and males and females were equally susceptible. Liver weights of the toxin plus CTR treated rats were similar to those in vehicle‐treated rats. When the toxin was administered into a similarly isolated jejunal loop, liver weight was significantly less than that found when an equivalent dose was administered into the ileal loop suggesting an intestinal site specificity for toxin a

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00625.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:α‐Mercapto‐β‐(2‐furyl) acrylic acid (MFA), α‐mercapto‐β‐(phenyl) acrylic acid (MPA), α‐mercapto‐β‐(2‐hydroxyphenyl) acrylic acid (MHA), α‐mercapto‐β‐(4‐methoxyphenyl) acrylic acid (MMA), β‐1,2‐phenylene di‐α‐mercapto acrylic acid (1, 2‐PDMA) and β‐1, 4‐phenylene di‐α‐mercapto acrylic acid (1, 4‐PDMA) enhanced faecal excretion and reduced liver, spleen and blood burden of inorganic mercury when administered (0.5 m mol/kg, in two split doses) 24 hr after Hg (II) (1 mg/kg) in rats. MFA, MPA, MHA and MMA were also effective in lowering renal Hg mainly from the cytosol, without any significant increase in urinary excretion of Hg. The results indicate that all the mono‐mercapto acrylic acids including MFA were more effective than di‐mercapto acrylic acids and act through the mechanism characteristic of thiol chelators, that is, mobilization of Hg as their complexes, contrary to the reported o

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00626.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:Kynurenic acid and ketamine are, besides non‐specific actions, antagonists of excitatory acidic amino acids in the rat brain. At intraperitoneal doses of 300 mg/kg (1.6 mmol/l) and 5 mg/kg (18 mmol/l), respectively, they are equipotent antagonists of N‐methyl‐D‐aspartate receptors. We studied the acute effects of ketamine and kynurenic acid, at these doses, on sleep patterns of rats during the second and third postnatal weeks with the so called static charge sensitive mattress (SCSB). Both kynurenic acid and ketamine decreased active sleep; ketamine additionally increased quiet state and kynurenic acid increased waking. The decrease in active sleep may be related to glutaminergic NMDA and serotonergic responses in the rat brain but non‐specific actions and interactions with other transmitter systems are also

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00627.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The effect of the calcium antagonist, diltiazem, was examined in gentamicin‐induced nephrotoxicity states in rats. Animals were injected for 5 days with diltiazem intraperitoneally (40 mg/kg/day), or gentamicin subcutaneously (100 mg/kg/day) or simultaneously with both preparations using the same doses. At the time of sacrifice, the urea and creatinine clearances, as well as urine osmolality were determined and the renal tissues were processed for examination by light microscopy. Gentamicin‐injected rats demonstrated the typical pattern of aminoglycoside nephrotoxicity characterized by poliuric renal failure and necrosis of the proximal tubular epithelium. Rats injected with diltiazem revealed only mild depression of urine osmolality. There was no elevation of blood urea nitrogen and serum creatinine or depression of urea and creatinine clearances, and no focal tubular cell necrosis was detected. However, concomitant administration of both compounds considerably increased nephrotoxicity by according both histological indications and renal function measurements. Thus, we conclude that the combination of diltiazem and gentamicin must be used carefully in human clinical pract

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00628.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The chorio‐allantoic membrane of explanted chick embryos can be used for the study of vascular development and of the vascular response to drugs and to tissue implants or tissue extracts. Three different types of vials for shell‐less cultivation of chick embryos were compared in terms of short‐term survival. Plastic cups with rounded bottoms were superior to Petri dishes and polyethylene film bags, in that they combined a high survival rate of the embryos with a possibility of using a large number of embryos in each experiment. With the use of plastic cups this method is simple, reliable and inexpe

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00629.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:We have studied the localization and affinity of methyl mercury hydroxide (MeHg) binding sites on microtubules. There is one class of binding sites for MeHg on tubulin, a high affinity class with fifteen sites. MeHg binds to tubulin stoichiometrically within microtubules, and does not induce microtubule disassembly at this low binding ratio. MeHg binds in microtubules either in the presence or absence of free tubulin subunits but free subunits act as uncompetitive inhibitors for MeHg binding to the polymer. These stoichiometric polymer surface binding sites for MeHg apparently do not interfere with subsequent polymerization, in contrast to the multiple sites in the free dimer whose occupation blocks subsequent assembly. In assembly cycles that follow MeHg binding to polymers, we continue to find MeHg bound to microtubules at substoichiometric ratios. Dimers with higher levels of MeHg binding are rendered assembly incompetent. These results show MeHg to have one class of binding site on tubulin, and the MeHg binding site, both to the polymer surface and to the free dimer, to be the same.

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00630.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The main purpose of these experiments was to study whether the morphine‐induced changes in cerebral noradrenaline (NA) turnover differ between various brain areas of male Wistar rats assessed by the α‐methyl‐p‐tyrosine (αMT)‐induced NA depletion. The effects of repeated saline injections (20 days) on the morphine‐induced changes in NA and also in free and sulphated 3‐methoxy‐4‐hydroxyphenylethylene glycol (MOPEG) concentrations were studied. 5 to 40 mg/kg of morphine reduced the αMT‐induced NA depletion in the cortical hemispheres, while 40 mg/kg of morphine enhanced it in the lower brain stem. 10 mg/kg of morphine lowered the NA concentration in limbic forebrain and hypothalamus and increased it in the cortical areas. It also elevated the MOPEG concentrations in all brain parts with the sole exception of sulphated MOPEG in the cortical hemispheres. Naltrexone antagonized the morphine‐induced changes in NA turnover and MOPEG concentrations. The only significant handling‐induced change was the elevation of NA concentrations in the hypothalamus. The increasing effect of morphine on the sulphated MOPEG concentration in the prefrontal cortex and the lower brain stem was attenuated in handled rats. In conclusion, these findings show that, the response of cortical NA neurones to acute morphine administration is retardation of turnover rather than activation which occurs most notably in the lower brain stem. Furthermore, the responses are modified by previous ex

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb00631.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY