摘要:

Abstract:The effects of low (5 mg/kg × 7) and high (20 or 30 mg/kg × 7) doses of cyclophosphamide on the formation an solubility of collagen in subcutaneous, porous implants, bones and incisional skin wounds were studied in young, male rats. At the 5 mg/kg schedule, effects from the drug were only detected as an increased solubility of collagen in implant connective tissue. At the 20 mg/kg schedule, there was a significant reduction of the synthesis and solubility of collagen in bones and in skin wounds. The 30 mg/kg schedule significantly depressed all the parameters studied except the specific activity of hydroxyproline in implants. Collagen stability seems to be impaired at low dose levels, whereas one of the main effects of high doses appears to be inhibition of collagen synthesi

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01623.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The metabolism of collagen and mineral was studied during a nine‐day postmedicational period in young, male rats receiving high‐dose intraperitoneal cyclophosphamide treatment every second day for 12 days. Two days after ending medication the white blood cell counts (WBC) were reduced by about 70%. Both synthesis and solubility of collagen were suppressed by the present medication 2 days after termination of treatment. This suppression continued throughout the 9‐day postmedicational period in bones, whereas in connective tissue of porous, ceramic implants both total collagen and the amount of salt soluble collagen regained normal values 9 days after cessation of treatment. Increased mineralization was found 2 days after ending medication and this high degree of mineralization persisted during the postmedicational period studied. Serum albumin levels were reduced and no increases were detected during the postmedicational period. The suggestion is made that the general protein synthesis is affected by high‐dose cyclophosphamide adminis

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01624.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Granulation tissue was produced by subcutaneous implantation of viscose‐cellulose sponges on rats. The effect of D‐penicillamine 500 mg/kg/day for 10 days on granulation tissue and the connective tissue of skin, bone and aorta was studied by comparison of treated animals with operated and unoperated controls. In addition, the effect of sponge implantation on intact tissues was studied by comparison between the control groups. The amount of granulation tissue was not affected by D‐penicillamine, and the granuloma‐DNA content even increased. D‐penicillamine increased the amount of salt soluble collagen in all tissues consistent with an inhibition of collagen crosslinking as reflected by increased aldehyde content and α/β chain ratio in soluble skin collagen. Skin appeared to be most sensitive. The content of free hydroxyproline and RNA and the RNA/DNA ratio in skin decreased suggesting a decreased collagen biosynthesis. The hydroxylation of proline and lysine was not affected by the treatment. The water percentage of aorta increased during D‐penicillamine treatment, and the35S‐sulphate uptake in the sulphated glycosaminoglycans was stimulated in all tissues, in granulation tissue mainly in the chondroitin‐4/6‐sulphate fraction. No quantitative glycosaminoglycan changes occurred in granulation tissue. Sponge implantation caused an increase in the amount of salt soluble skin collagen without any change in α/β chain ratio and aldehyde content of purified, soluble collagen. D‐penicillamine plus operation reduced the collagen content of aorta. The effects of D‐penicillamine on connective tissue compounds may be of importance for its antirheumatic efficacy, but the accompanying effect on normal tissu

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01625.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:A possible involvement of cyclic nucleotides (cAMP and cGMP) in the regulation of cardiac contractility and glycolysis during hypoxia was examined in spontaneously beating rat atria. A reduction of the high oxygen saturation (HiOxSa) of the incubation medium from 95–100% to half produced a rapid decline of the amplitude. The deterioration of 50% was seen after 30 sec. of hypoxia. The decline was partly antagonized by noradrenaline (NA, 1×10−6M) or hypercalcaemia (5.7×10−3M instead of 1.9×10−3M). The cAMP level remained unchanged during the first 12 min. of hypoxia, but the cGMP content increased gradually and reached a significantly increased level in 4–8 min. Paradoxically, the production of lactate decreased, after 30 sec. of hypoxia, but accelerated then 2–4 min. after the onset of hypoxia. The depletion of creatine phosphate and ATP stores was initiated after 2 min. of hypoxia. The atrial content of the active forms of phosphofructokinase and lactate dehydrogenase gradually rose during hypoxia. Sodium nitroprusside (SNP, 1×10−4M) and NA produced increases in cGMP and cAMP levels, respectively, both in HiOxSa and hypoxia. SNP induced a slight and NA a marked increase in the amplitude in HiOxSa. Verapamil (1×10−6M) decreased the contractility, but did not affect the levels of cAMP or cGMP. Both SNP and verapamil decreased the lactate production, but they could not resist the NA‐induced increase in the atrial lactate level. Hypercalcaemia increased the amplitude but slightly reduced the lactate production in HiOxSa.45Ca‐uptake was reduced to about 35 per cent of control as measured between 5 and 10 min. of hypoxia. It is concluded that the lack of oxygen could have direct and parallel effects on the sarcolemma and on the mitochondria. The former could result in the deterioration of contractility and the latter in the termination of aerobic energy production. Cyclic nucleotides are not involved in either of these phenomena. However, at the low rate of anaerobic glycolysis, e.g. in HiOxSa or at the very early stage of hypoxia, cGMP could inhibit and cAMP accelerat

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01626.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The mechanism of the GABAergic inhibition of the TSH cold‐response was studied in male rats. Picrotoxin, a putative GABA receptor antagonist (4 mg/kg but not 0.5 or 2 mg/kg intraperitoneally) significantly decreased the cold‐stimulated TSH secretion but did not modify the TRH‐induced (100 ng intraperitoneally) TSH‐response. The inhibitory effects of two GABAergic drugs muscimol (1 mg/kg subcutaneously) and aminooxyacetic acid (10 mg/kg intraperitoneally) were not antagonized by picrotoxin (1–4 mg/kg intraperitoneally), by phenoxybenzamine (2.5 or 5 mg/kg intraperitoneally), by two 5‐HT antagonists cyproheptadine (5 mg/kg intraperitoneally) and R 41468 (2.5 mg/kg intraperitoneally) or by pimozide (0.5,1.5 or 2.5 mg/kg subcutaneously). The results suggest that neither picrotoxin‐sensitive GABA receptors nor noradrenaline, 5‐HT or dopamine pathways seem to be involved in the inhibitory action of GABAergic drugs on the TSH cold‐resp

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01627.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The distribution of an intravenous glucose load was investigated in rats without and with previous lithium administration. Lithium caused an increased rate of glycogen formation in muscle tissue but not in liver tissue. Uptake of a14C‐labelled glucose load in skin, liver, muscle, fat and brain was measured. Lithium increased the uptake of labelled glucose in skin and muscle with a concomitant decrease of the amount in blood. The findings are in agreement with an increased glucose tolerance after lithium administration as the uptake was increased in the tissues of quantitative importance for the disposal of a glucose loa

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01628.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The myocardial accumulation and disposition pharmacokinetics of the antianginal and antihypertensive calcium‐antagonistic drug nifedipine were investigated in isolated, perfused and spontaneously beating rabbit hearts. The myocardium behaved pharmacokinetically as a two‐compartment system with regard to the drug. The mean half‐lives of the α‐phase of distribution and of the β‐phase of disposition were about 1.2 and 6.5 min., respectively. Perfusion with a modified Krebs‐Henseleit solution containing nifedipine in a concentration of 50 ng ml−1caused an accumulation of about 1277 ng g‐1 in the myocardium at steady state. Stepwise increased concentrations of nifedipine from 3 to 60 ng ml−1in the liquid used in perfusions for 25 min. periods produced a pronounced progressive decrease in myocardial contractility to about 8%. The heart beating frequency simultaneously decreased gradually to about 76%. The mean coronary flow rate increased initially to 135% and then gradually decreased to 94%. These effects were accompanied by a decrease to about 0.27 in the ratio of the product of contraction amplitude and frequency to the oxygen consumption, a finding that was evaluated as an expression of reduced myocardial efficiency. No significant dromotropic ef

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01629.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The phenylethanolamine D2343 exhibits a dualistic adrenoceptormediated effect, i.e. a β‐agonistic effect combined with an α‐antagonistic one. Tracheal smooth muscles and heart preparations were used to gauge the agonistic effect on adrenergic β‐receptors. Rabbit aorta and rat vas deferens were used to determine the α‐adrenoceptor blocking activity. The β‐adrenoceptor activity of D2343 was classified as β2‐type with about the same efficacy as the β2‐selective terbutaline on tracheal muscle. The effect on isolated heart preparations was greater than that produced by terbutaline. The α‐receptor blocking capacity was directed against the α1‐receptor type and was of nearly the same p

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01630.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The effect of short‐term exposure of manganese on the synthesis of brain catecholamines in growing rats has been investigated by using two methods, 1) measuring the amount of conversion of 3,5‐3H‐tyrosine to3H‐labelled dopamine and norepinephrine, and 2) measuring the rate of decline of endogenous dopamine and norepinephrine following inhibition of their synthesis with α‐methyl‐p‐tyrosine. The magnitude of conversion of 3,5‐3H‐tyrosine to3H‐dopamine and3H‐norepinephrine in the brain at 60 min after the administration of labelled amino acid to the manganese treated rats (1 mg MnCl2.4H2O/ml of water for 30 days) was significantly greater than observed in control rats. Manganese also increased turnover of dopamine and norepinephrine to a greater extent in the bra

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01631.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:In pregnant NMRI mice, low‐temperature autoradiography was used to study the distribution of N‐14C‐nitrosodiethylamine in foetal tissues, and autoradiography with heated tape‐sections was used to trace nonvolatile metabolites. Autoradiography with14C‐acetate was used to distinguish the part of the radioactivity which upon the degradation of N‐14C‐nitrosodiethylamine may be incorporated in the normal metabolism of the tissues. The results indicated that the non‐metabolized N‐nitrosodiethylamine passed to the foetuses with an even distribution in most foetal tissues on all the studied days of gestation (day 12, 14, 16 and 18). The autoradiographic results further indicated a metabolism of the substance in the mucosa of the foetal bronchial tree and in the foetal liver on day 18 of gestation, but not in earlier stages of pregnancy. This was substantiated by studiesin vitro, which showed a marked capacity of the 18 day old foetal lung and liver (in contrast to tissues from 16 day old foetuses) to form14CO2from the N‐14C‐nitrosodiethylamine. Since the lung and liver are target tissues for the transplacental carcinogenesis of N‐nitrosodiethylamine in NMRI mice, a causal relationship between metabolic ability and carcinogenesis may

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01632.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY