摘要:

Abstract:The effect of intravenously administered prostaglandin F2αon gastric acid secretion was investigated in anaesthetized rats. Doses of 0.03–0.3 mg/kg PGF2αstimulated gastric acid output in rats with intact vagi, whereas an inhibitory effect was observed in vagotomized animals. Treatment with 5 mg/kg of Na‐meclofenamate intravenously attenuated the secretory response to PGF2α, while 10 mg/kg of indomethacin intravenously and 3 mg/kg of 8‐phenyltheophylline intraperitonelly were without any effect. The results indicate that intravenously administered PGF2αstimulates gastric acid secretion in anaesthetized rats via activation of the vagus nerve. The effects of Na‐meclofenamate and indomethacin suggest that PGF2αmay exert its secretagogue action via specific receptors. The lack of the effect of 8‐phenyltheophylline indicates that adenosine which reportedly had a similar effect on gastric secretion after intravenous injection seems not to be

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb00941.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:Bambuterol, the bis‐dimethyl carbamate prodrug of terbutaline, and physostigmine were examined with respect to their ability to interfere with the neuromuscular transmission in an isolated vagus nerve‐trachea preparation, a phrenic nerve‐diaphragm preparation and the transmurally stimulated extensor digotorum longus (EDL) isolated from the guinea‐pig. Physostigmine increased the contractile response of the trachea to stimulation of the vagus nerve. Bambuterol had an opposite effect in this respect and inhibited the effect of physostigmine. Both compounds, in high concentrations, increased the tension of the unstimulated tracheal smooth muscle. Physostigmine, but not bambuterol, caused a threefold increase in the twitch tension of the indirectly stimulated diaphragm. Bambuterol counteracted this increase almost completely. In the EDL, physostigmine caused a concentration‐dependent and curare‐sensitive increase in the force of both twitches and subtetanic contractions. This increase was completely inhibited by bambuterol which had no effectper seon the contractions. Both enantiomers of bambuterol appeared to be equally potent in counteracting the effect of physostigmine on the EDL. It is concluded that bambuterol, in concentrations which selectively and completely block the butyrylcholinesterase, has no effect on the neuromuscular transmission. In higher concentrations, at which bambuterol might interfere with acetylcholinesterase, it counteracts the effects of the unselective inhibitor of cholinesterases, ph

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb00942.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:The macrolide antibiotics are metabolized by cytochrome P‐450 enzymes in the liver and interactions with similarly metabolized compounds have been described. Simultaneous treatment with erythromycin and warfarin is known to decrease warfarin clearance and prolong prothrombin time. Roxithromycin (RU 28965), a new erythromycin derivative with improved pharmacokinetic properties, might then, because of structure similarity, be expected to interact with warfarin. In 21 healthy volunteers, the effect of orally administered roxithromycin (150 mg b.i.d.) on warfarin steady‐state kinetics, and the effects of warfarin on roxithromycin kinetics, were investigated in a double‐blind, randomized study versus placebo. Since the warfarin enantiomers, R‐ and S‐warfarin have both different potency and different metabolism, the ratio between the enantiomers with and without roxithromycin, was also determined. In this study, mean AUC for warfarin increased slightly from day 14 of warfarin treatment to day 28, but no difference was found between the roxithromycin group and the placebo group, and no change appeared in the ratio between the warfarin enantiomers. A moderate increase in dosage was needed to maintain hypocoagulability during warfarin medication, but there was no difference between the roxithromycin group and the placebo groups, respectively. In addition, roxithromycin kinetics appeared to be unaffected by warfarin

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb00943.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:The interaction of some cations with the enzymatic activity of soluble protein kinase C was determined in order to elucidate whether protein kinase C can be activated by other metal cations besides Ca2+. Protein kinase C was activated by Ca2+and Sr2+having EC50 values of nearly 10 μM and 200 μM, respectively. Ba2+likewise activated protein kinase C but was less potent. Co2+, Ni2+and Mn2+had no activating effects on the activity in the absence of Ca2+, but was slightly reduced in the presence of Ca2+(0.5 mM). Cations with ionic radii close to Ca2+(0.99 Å) inhibited the activity irrespective of the absence or presence of Ca2+. The order of potency is as follows: Hg2+>Cd2+∼ Cu2+≫ Sm3+>Tb3+>La3+, Pb2+and Zn2+, which showed a high affinity to SH‐groups, as well as Hg2+, Cd2+and Cu2+, which also inhibited the activity. Thus, among the ions investigated, the alkaline‐earth ions Sr2+and Ba2+could be substituted for Ca2+, irrespective of ionic radii. The serious environmental pollutants such as Hg2+, Cd2+or Pb2+impaired the activity of protein kinase C probably due to S

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb00944.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:To investigate molecular mechanisms involved in the neurotoxicity of clioquinol (5‐chloro‐7‐iodo‐8‐hydroxyquinoline), the inhibitory effects of this drug on DNA, RNA and protein syntheses were examined, in relation to the action of nerve growth factor (2.5S NGF). We used an organ culture of neonatal rat superior cervical ganglion (SCG). Ten μM clioquinol inhibited completely DNA and protein syntheses and abolished the stimulatory effect of NGF on RNA synthesis. With regard to the chemical structure of clioquinol, hydroxylation at the 8th carbon of quinoline is essential for the inhibition of DNA, RNA and protein syntheses, and the hydrophobicity of the 8‐HQ derivatives is a required property for potent inhibition. Compared with effects of EDTA, alizarine, sodium alizarine sulfate, o‐phenanthroline and α,α′‐dipyridyl, the loss of the NGF‐induced stimulation of RNA synthesis by clioquinol does not seem to be primarily caused by its metal‐chelating property. Clioquinol did not significantly alter the uptake rate of thymidine, uridine and leucine, thereby suggesting that the primary action of clioquinol on inhibition of DNA, RNA and protein syntheses does not relate to uptake of the precursor into SCG. Clioquinol did not significantly alter the degradation of3H‐uridine‐labeled RNA. NGF suppressed the degradation of RNA and this suppression was overcome by clioquinol. The release of free uridine from SCG into the culture medium was enhanced by clioquinol and was partially suppressed by NGF. The inhibitory effects of clioquinol were completely prevented by bovine serum albumin (BSA), but not by NGF even at a 5‐fold concentration of clioquinol. Clioquinol also inhibited the synthesis of RNA, stimulated by pretreatment of SCG with NGF. These results suggest that the inhibitory effects of clioquinol on RNA synthesis stimulated by NGF and on the suppressed RNA‐degradation by NGF are due to actions on the intracellular processes of RNA synthesis and degradation rather than to interference at the receptor site of N

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb00945.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:The effects of the stimulant drugs, d‐amphetamine and methylphenidate, upon the motor activity of male and female off‐spring of pregnant rats, treated on gestation day 15 with the antimitotic agent methylazoxymethanol (MAM, 25 mg/kg) were studied in four experiments. Cortical and striatal hypoplasia induced by prenatal administration of MAM resulted in increased concentrations of catecholamines in those regions. Administration of d‐amphetamine and methylphenidate caused significant increases in motor activity; this effect was markedly potentiated in the MAM‐treated rats, both the male and female off‐spring. Thus, the locomotion and total activity parameters showed similar, but not identical, drastic increases in behaviour induced by the stimulant drugs as a result of the prenatal MAM treatment whereas for the rearing parameter a lesser potentiation by the MAM treatment was observed. This potentiation of the excitatory effects of the stimulant compounds upon the behavioural parameters is interpreted in terms of a relative increase in the density of catecholaminergic terminals in the forebrain regions of the central nervous system. The present results are discussed with regard to the utility of prenatal MAM treatment as a possible animal model for certain neurological

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb00946.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:A salient sign of fatal 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) intoxication is dramatic body weight loss accompanied by hypophagia. Yet, the nature of this wasting syndrome is unknown. As all of the current leptogenic (weight reducing) drugs exert their action by affecting aminergic neurotransmission, this study set out to screen the reversibility of TCDD‐induced anorexia with the following agents modulating aminergic neurotransmission: amphetamine, amperozide, chlordiazepoxide, clonidine, haloperidol, morphine, PCPA, phenoxybenzamine, reserpine and sotalol. In addition, dexamethasone, indomethacin, and insulin were included in the drug battery. The agents were administered subcutaneously to adult male Long‐Evans rats over a period lasting from 3 to 14 days. Half of each drug group was concomitantly exposed to a lethal dose of TCDD (20 μg/kg). None of the regimens were able to mitigate the wasting syndrome. TCDD proved to markedly diminish the nocturnal feed intake while practically sparing daytime feed consumption. Insulin increased the daytime feeding of TCDD‐exposed rats, and the termination of treatment resulted in almost total aphagia in this group. Amphetamine, dexamethasone, PCPA, and reserpine caused weight loss in drug control rats and aggravated the action of TCDD. However, clonidine had no effect on the weight of control rats but accelerated weight decline in TCDD‐cotreated animals. TCDD seemed to have a somewhat minor influence on drinking than on feeding. Clonidine stimulated water intake in controls but not in TCDD‐exposed rats. These results suggest that aminergic neurotransmission is not specifically or crucially affected by TCDD, but further studies are needed to confirm

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb00947.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:Triethyl lead chloride (TEL) was added directly to female rat liver microsomal fractions at final concentrations of 0.0, 0.005, 0.05 and 0.5 mM, respectively. The effect of oestradiol on liver microsomal metabolism was studiedin vitroby incubating the microsomes with radioactive oestradiol‐17β. The oestradiol metabolites were separated, identified and quantified. The highest treatment concentrations resulted in decreased activities of enzymes that metabolize oestradiol

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb00948.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:Female mice were injected intraperitoneally daily from day 18 of gestation and throughout lactation with triethyl lead chloride (TEL; 0.0, 0.5 and 1.0 mg/kg body wt). Off‐spring of treated mothers displayed a slight perinatal growth retardation. Male off‐spring appeared to be more sensitive to TEL, as indicated by their lower body weights. During the latter half of the lactation period the treated sucklings grew faster than controls, thereby compensating for their initially retarded growth, by the time of weaning. The hepatic cytochrome P‐450 content of 9 to 10‐day old sucklings of treated mothers was lower than in corresponding controls. We suggest that perinatal growth retardation is initiated by a disturbance in the uterus, e.g. reduced nutrient transport across the p

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb00949.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Abstract:Pigs, crossbreeds of Swedish Landrace and Yorkshire, females and castrated males about 6 months old, were exposed to experimental stress. The pigs were either considered normal or shown to be susceptible to develop malignant hyperthermia when tested with halothane at about 6 weeks of age (stress‐susceptible pigs). The stress was of the restraint type, produced by two different myorelaxant agents, the depolarizing succinylcholine or the non‐depolarizing pancuronium. The blood levels of the catecholamines (CA) noradrenaline (NA) and adrenaline (A) were measured during the stress. The severity of myocardial cell necrosis observed 1 to 2 days after the stress was morphologically graded. Innormalpigs the levels of NA during the stress and the degree of myocardial cell necrosis were about the same after both succinylcholine and pancuronium. Instress‐susceptiblepigs, however, succinylcholine produced very high NA and A levels and severe heart lesions, whereas after pancuronium the NA and A levels were rather low and the heart lesions significantly reduced when compared to those after succinylcholine‐induced stress. After pretreatment with dantrolene intravenously the succinylcholine‐induced stress only induced slightly increased blood CA levels and no signs of myocardial cell necrosis in pigs susceptible to develop malignant hyperthermia. Dantrolene, an efficient drug in treatment of malignant hyperthermia, probably acts by interfering with release of calcium from the sarcoplasmic reticulum in skeletal muscles. The results indicate that peripheral sympathetic neurones in MHS pigs also react abnormally, probably due to defective calcium

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1988.tb00950.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY