摘要:

The influence of aging and the effects of treatment with dihydrogenated rye ergot alkaloid on cerebral hemodynamics and metabolism were studied in Long-Evans rats. Cerebral blood flow (CBF) was not affected by aging whereas the vascular bed and the uptake of deoxyglucose were significantly lower in aged than in young rats. 20 days after ligation of a carotid artery the blood flow on the same side of the brain, the vascular bed and the uptake of deoxyglucose were significantly lowered in aged rats as opposed to young rats. The second carotid artery was ligated 1 h before the animals were sacrificed: in the corresponding cerebral hemisphere the blood flow was found to be significantly lowered in young rats and even more so in aged rats. These results show that young rats are more likely to adapt to an acute or chronic circulatory deficiency than aged rats. Dihydroergocryptine (DHEC, 0.1 mg/kg/day for 5 days, p.o.) reduces CBF and the vascular bed in aged rats, as opposed to dihydroergotoxine (DHET, 5 × 0.1 mg/kg/day p.o.). The uptake of deoxyglucose was not influenced by the treatments. After ligation of the carotid arteries, treatment with DHEC and DHET induced an increase in CBF without any change in the vascular bed and, in the case of DHEC only, there was a significant increase in the uptake of deoxyglucose in the cerebral hemisphere submitted to acute circulatory deficiency. DHEC and DHET thus exerted significant effects on cerebral metabolism and hemodynamics in the aged rats after repeated oral treatment

ISSN:0031-7012    

DOI:10.1159/000137970

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The effects of fusaric acid and verapamil on 15-hydroperoxyarachidonic acid (15-HPAA)-induced cerebral arterial contraction were examined. Addition to the tissue bath of 15-HPAA in concentrations ranging from 1 × 10–7 to 3 × 10–5M caused a dose-dependent contraction in canine basilar, middle cerebral, posterior cerebral and human basilar or middle cerebral arteries. Fusaric acid and verapamil antagonized the 15-HPAA-induced contraction of these cerebral arteries by different mechanisms, in a dose-dependent manner. In the presence of 1 × 10–3M fusaric acid, the dose-response curves of cerebral arteries for 15-HPAA were antagonized in a noncompetitive manner. However, the responses to 15-HPAA were restored completely after removal of fusaric acid from the bathing solution. Fusaric acid did not antagonize the CaCI2-induced contraction. The concentration of verapamil which antagonized the 15-HPAA-induced contraction was a good fit to the concentration of this antagonist which antagonized the CaCb-induced contration. These findings indicate that the antagonism seen with fusaric acid manifests as a block of the sites specific for 15-HPAA and that the antagonistic actions of verapamil on 15-HPAA may be produced by the inhibition of calciu

ISSN:0031-7012    

DOI:10.1159/000137971

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Cimetidine, an H2 receptor antagonist, administered into a lateral ventricle of the rat brain caused a significant increase in tail flick latency. Dimaprit, a specific H2 agonist, failed to counteract the analgesic effect of cimetidine. In contrast, it enhanced the effect of cimetidine and per se had marked analgesic activity. The specific opioid antagonist naloxone was without effect. Pretreatment with CaCI2 completely prevented the action of cimetidine. These findings suggest that the analgesic action of cimetidine and dimaprit is not due to specific effects on H2 receptors.

ISSN:0031-7012    

DOI:10.1159/000137972

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The effect of cimetidine and two new histamine H2-receptor antagonists, oxmetidine and SKF 93479, on histamine-stimulated adenylate cyclase activity was studied in guinea pig gastric mucosal cells. Histamine stimulated the enzyme activity in a concentration-dependent fashion. The concentration-response curve of histamine was progressively shifted to the right in the presence of increasing concentrations of each antagonist. The Schild plot gave a straight line for all three compounds, with a slope not significantly different from unity and this suggested a competitive antagonism. The calculated pA2 values were 8.45 ± 0.20, 7.73 ± 0.21 and 6.81 ± 0.15 for SKF 93479, oxmetidine and cimetidine, respectively. These results are in accordance with the pharmacological potencies of the antagonists reported on isolated heart preparation and on gastric secretion in vivo. Therefore, the inhibition of histamine-sensitive adenylate cyclase of gastric cells may represent an additional tool for the in vitro evaluation of the H2-receptor antagonis

ISSN:0031-7012    

DOI:10.1159/000137973

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The effect of 16, 16-dimethyl prostaglandin E2 (DmPGE2), in doses subthreshold for antisecretory activity, were examined in female rats. The aims were to determine if DmPGE2 alters the disposition of acetylsalicylic acid (ASA) within the gastric mucosa and if DmPGE2 could attenuate the ulcerogenic effect of oral ASA. Gastric lesions occurred after an oral, but not an intravenous dose of 150 mg/kg ASA. Lesions could be prevented by pretreatment with 5 μg/kg DmPGE2 orally 30 min prior to ASA. DmPGE2 elevated fundic concentrations of both ASA and salicylic acid (SA) within the first hour when ASA was given orally. The ratio of the concentration of ASA/SA in fundus was not changed, indicating that DmPGE2 did not depress the fundic esterase activity. It is concluded that the cytoprotective effect of DmPGE2 is not related to a change in mucosal concentration or elimination of ASA or SA

ISSN:0031-7012    

DOI:10.1159/000137974

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

We investigated the role of protein synthesis in human polymorphonuclear leukocyte (PMN) chemotaxis and luminol-dependent chemiluminescence (CL). We used cycloheximide and puromycin to inhibit protein synthesis, and determined the extent of synthesis by measurement of 14C-amino acid incorporation. With 2-hour incubations both puromycin at 9.0 × 10–6 M and cycloheximide at 1.8 × 10–6M inhibited PMN protein synthesis. At concentrations of 2–4 × 10–5M both cycloheximide and puromycin inhibited PMN-chemotaxis 40 and 55%, respectively. However, inhibition was observed only when using zymosan-activated serum and not formylmethionyl-phenylalanine as a chemoattractant. Using 2-hour incubations, PMN-CL was also suppressed by puromycin and cycloheximide, at 20 and 40%, respectively. The data demonstrated that protein synthesis had an important role in chemotaxis that was dependent on the chemoattractant and perhaps the cellular receptor involved in that process. CL did not require de novo protein synthesis but appeared to depend on protein(s) with a relatively rapi

ISSN:0031-7012    

DOI:10.1159/000137975

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Our previous studies have demonstrated that chlorpromazine (CPZ) and imipramine (IMP) are metabolized appreciably via N-oxidation catalyzed by pulmonary microsomal flavin monooxygenase in the rat but not in the rabbit. The present work deals with the species differences in N-oxidase of pulmonary microsomes from male cat, dog, goat, guinea pig, hamster, mouse, pig, rabbit and rat. Although CPZ-N-oxidizing activities were generally higher than IMP-N-oxidizing activities, the CPZ-/IMP-oxidizing activity ratios were not constant among the species tested. Little or no activity was detected in the guinea pig and rabbit lung. The following ranking was assigned: mouse < hamster < pig < rat < dog < cat < guinea pig < goat < rabbit for CPZ, and pig < rat < mouse < dog < hamster < cat < guinea pig < goat < rabbit for IMP. Nitrosobenzene, a known inhibitor of N-oxidase reductase, inhibited rather than increasing the N-oxidation of both substrates. Therefore, it is unlikely that the marked species differences in pulmonary N-oxidase activities are due to differences in N-oxide reductase. Optimum pH for CPZ-N-oxidase was relatively broad over a range of 7.4–8.5 for rat and 8–9.5 for other species. The pH optima for IMP-N-oxidase ranged from 8.5 to 9.5. n-Octylamine accelerated CPZ-N-oxidation in most species. IMP-N-oxidation was affected to a lesser extent by this primary amine. DPEA (2,4-dichloro-6-phenyl-phenoxyethylamine) also stimulated the CPZ-N-oxidation in rat, pig and cat but inhibited IMP-N-oxidation in these species. These findings suggest that significant species differences exist in pulmonary N-oxidase activity and that the CPZ and IMP-N-oxidases may be represented by two different microsomal flavin amine oxida

ISSN:0031-7012    

DOI:10.1159/000137976

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The LD50 was determined for 5-fiuorouracil (FU) in mice at 11.00 and 23.00 h during one 24-hour period. These times were chosen because in mice kept on a light-dark cycle, with lights on from 06.00 to 18.00 h, the natural circadian rhythm in DNA synthetic activity in many different normal organs attains peak levels around 24.00 h (mid-dark) and through levels around 12.00 h (mid-light). The LD50 of FU, in milligrams per kilogram body weight, was much higher (450–500 mg/kg) at 11.00 than at 23.00 h (250–300 mg/kg). Since the biology of the living animal oscillates significantly on a daily or circadian basis, it is understandable that the degree of susceptibility or resistance to drugs should also fluctuate over the circadian period. Determination of the LD50 of a drug at that point in time when the animal is naturally resistant to that drug will result is a false appraisal of the toxic effects to the drug. To assess correctly the risk a drug poses, it should be tested at its time of maximal susceptibility in the living ani

ISSN:0031-7012    

DOI:10.1159/000137977

出版商:S. Karger AG    

年代:1984

数据来源: Karger