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61.
Rainer Schulz Ron J. Oudiz Brian D. Guth Gerd Heusch 《Naunyn-Schmiedeberg's archives of pharmacology》1990,342(4):422-428
Summary -Adrenoceptor-mediated coronary vasoconstriction contributes to the initiation and aggravation of experimental and clinical myocardial ischaemia. However, the extent of 1- and 2-adrenoceptor-mediated constriction has not been characterized in the porcine coronary circulation despite the frequent use of this experimental model.Fifteen swine were anaesthetized with either -chloralose, enflurane or isoflurane to determine the amount of -adrenoceptor-mediated coronary constriction elicited by either the selective 1-adrenoceptor agonist methoxamine or the selective 2-adrenoceptor agonist azepexole. The left anterior descending coronary artery was cannulated and perfused by an external pump delivering constant blood flow from the carotid artery. Following bilateral cervical vagotomy and ß-adrenoceptor blockade with propranolol (2 mg kg–1), graded dosages of either one of the -adrenoceptor agonists (9–45 g kg–1 min–1) were infused into the coronary perfusion line while coronary arterial pressure (CAP) was measured through a distal side arm of the cannula to detect changes in coronary vascular resistance. Infusion of the -adrenoceptor agonists was terminated when systemic arterial pressure increased. Sonomicrometers were used to measure anterior left ventricular wall thickening for the assessment of regional contractile function. During methoxamine infusion, no increase in vascular resistance was observed during -chloralose, enflurane or isoflurane anaesthesia, whereas the infusion of azepexole increased CAP from 103 ± 31 mmHg to 120 ± 35 mmHg (-chloralose), from 101 ± 16 mmHg to 122 ± 11 mmHg (enflurane) and from 84 ± 20 mmHg to 94 ± 19 mmHg (isoflurane), respectively. In four additional swine anaesthetized with enflurane, the intracoronary infusion of the full catecholamine agonist noradrenaline in the presence of propranolol (6 mg kg–1) increased CAP from 98 ± 10 to 105 ± 10 mmHg prior to an increase in regional left ventricular function or systemic arterial pressure.These results indicate that there are no 1- and relatively little 2-adrenoceptor-mediated coronary constrictive effects in swine. Furthermore, neither -adrenoceptor agonist produced any detectable change in regional myocardial contractile function, regardless of the anaesthesia used.Supported by the German Research Foundation (He 1320/3-2). Dr. Guth is the recipient of a scholarship from the Alexander von Humboldt-Foundation.
Send offprint requests to G. Heusch at the above address 相似文献
62.
H. Okuno Y. Kitao M. Takasu H. Kano K. Kunieda T. Seki Y. Shiozaki Y. Sameshima 《European journal of clinical pharmacology》1990,39(4):365-367
Summary The depressant effect of interferon- on drug metabolizing activity in the liver has been investigated in 12 patients with chronic active hepatitis B. 7-methoxy-coumarin (7-MC) O-demethylase and 7-ethoxycoumarin (7-EC) O-deethylase, in specimens obtained by liver biopsy, were measured before and after interferon treatment. 7-MC and 7-EC O-dealkylase activity were significantly reduced after interferon treatment, from 13.4 to 9.24 nmol·g–1 liver·min–1, and from 3.22 to 2.16 nmol·g–1 liver·min–1, respectively. The magnitude of the fall varied widely between individual patients. The study provides the first direct evidence that interferon- can impair the activity of drug metabolizing enzymes in the human liver. 相似文献
63.
The Liposome as a Model Membrane in Correlations of Partitioning with α-Adrenoceptor Agonist Activities 总被引:1,自引:0,他引:1
The apparent partition coefficients of a group of imidazoline -adrenoceptor agonists in liposome/buffer systems (Km) and in the n-octanol/buffer system (P) have been compared in quantitative structure–activity relationships (QSAR) employing biological activities and receptor binding affinities. A parabolic relationship between log K
m
and log P was found, and log K
m
was greater than log P for all liposome compositions. In liposomes, log K
m
decreased in the order, negatively charged > neutral > positively charged. Overall, hyper- and hypotensive activities of these drugs correlated better with log K
m
than with log P; however, poor correlations were obtained between partition coefficients and in vitro binding affinities. Linear correlations of log K
m
with hypotensive activities were obtained with negatively charged liposomes, whereas correlations with hypertensive activities were obtained using positively charged liposomes. Multiple regressions of biological activities with binding affinities showed positive correlations with hypotensive but not hypertensive activities with or without the inclusion of log K
m
or log P. Thus, the liposome represents a more selective model membrane system than a bulk oil phase for predicting the biological activities of imidazoline -adrenoceptor agonists. 相似文献
64.
利用CaCl2法成功地将寡核苷酸导入大肠杆菌JM109细胞。质粒pBR322转化结果表明,寡革酸片段5’-AGCGGGAATAAGGGAA-3’在转化前(或后)与靶序列结合均能抑制β-内酰胺酶基因的表达,细菌生长受到抑制。体外聚丙烯酰胺凝胶电泳结果表明,该片段能与靶序列形成三链结构。这些结果表明多聚嘌呤寡核苷酸是通过与靶序列形成三链DNA来抑制β-内酰胺酶基因的表达。 相似文献
65.
C. A. Schmidt A. Neubauer K. H. Seeger C. F. Rochlitz T. Binder H. Oettle G. Henze E. T. Liu D. Huhn W. Siegert 《Annals of hematology》1994,68(4):171-174
Summary Deletion of the short arm of chromosome 9p involving the 1-interferon (IFN) gene has been implicated in the process of malignant transformation in lymphomas and acute lymphoblastic leukemias. Since cytogenetic analysis is frequently unsuccessful in clinical samples, we used a recently described differential PCR technique to detect losses within the 1-IFN gene in 86 acute leukemias. Using differential PCR, no 1-IFN deletion was detected in 44 acute myeloid leukemia (AML) and eight control samples. However, five of 42 acute lymphoblastic leukemia (ALL) probes (12%) exhibited loss of the 1-IFN gene (three common ALL, two T-ALL). Cytogenetic analysis was performed independently in three of these five cases and revealed abnormalities of chromosome 9p in two samples. Two of five T-ALL cases exhibited a loss within the 1-IFN gene, compared with 3/29 c-ALLs, suggesting a predominance of IFN gene loss in T-ALLs. These data indicate that PCR can be used for rapid detection of gene dosage phenomena in clinical leukemia samples. 相似文献
66.
G. Skuza Z. Rogoz G. Quack W. Danysz 《Journal of neural transmission (Vienna, Austria : 1996)》1994,98(1):57-67
Summary Some treatments used for Parkinson's disease attenuate locomotor depression in rats treated with reserpine and -methyl-p-tyrosine. In the present study memantine (2.5, 5.0mg/kg), amantadine (10, 20mg/kg) (both uncompetitive NMDA antagonists), and L-deprenyl (1.0, 5.0 mg/kg; MAO-B inhibitor) were tested for possible synergistic interactions with the dopamine agonists: bromocriptine (2.5, 5.0mg/kg) and L-DOPA (50, 100mg/kg, + benserazide, 100 mg/kg). At higher doses, memantine (10 mg/kg), amantadine (40 mg/kg), bromocriptine (5 and 10mg/kg) and L-DOPA (100, 200mg/kg) but not L-deprenyl (up to 10 mg/kg) produced a pronounced increase in locomotor activity when given alone. The combination of memantine, amantadine and L-deprenyl with bromocriptine did not result in synergism of action and, at best, an additive effect was seen. On the other hand the combination of these agents with L-DOPA produced a pronounced synergistic effect. Hence, the clinical observation that coadministration of L-DOPA with either memantine or amantadine results in enhancement of their action is also reflected in an animal model of Parkinson's disease. Such a combination therapy should allow the use of lower doses of both drugs which may reduce the occurrence of side effects and may also be predicted to have additional benefits related to the neuroprotective properties of memantine, amantadine, and L-deprenyl. 相似文献
67.
Ossification and pseudoepiphysis formation in the “nonepiphyseal” end of bones of the hands and feet
J. A. Ogden M.D. T. M. Ganey Ph.D. T. R. Light M.D. R. J. Belsole M.D. T. L. Greene M.D. 《Skeletal radiology》1994,23(1):3-13
Metacarpals, metatarsals, and phalanges were studied to assess the developmental morphology of secondary ossification in the nonepiphyseal ends of these bones as well as the formation of the pseudoepiphysis as an epiphyseal ossification variant. Both direct ossification extension from the metaphysis into the epiphysis and pseudoepiphysis formation preceded, and continued to be more mature than, formation and expansion of the classic epiphyseal (secondary) ossification center at the opposite end of each specific bone. Direct metaphyseal to epiphyseal ossification usually started centrally and expanded hemispherically, replacing both physeal and epiphyseal cartilage simultaneously. In contrast, when remnants of physis were retained, while juxtaposed epiphyseal cartilage was replaced, a pseudoepiphysis formed. There were three basic patterns of pseudoepiphysis formation. First, a central osseous bridge extended from the metaphysis across the physis into the epiphysis and subsequently expanded to create a mushroom-like osseous structure. In the second pattern a peripheral osseous bridge formed, creating either an osseous ring or an eccentric bridge between the metaphysis and the epiphysis. In the third pattern, multiple bridging occurred. In each situation the associated remnant physis lacked typical cell columns and was incapable of significantly contributing to the postnatal longitudinal growth of the involved bone. Pseudoepiphyses were well formed by 4–5 years and coalesced with the rest of the bone months of years before skeletal maturation was attained at the opposite epiphyseal end, which ossified in the typical pattern (i.e., formation of a secondary center de novo completely within the cartilaginous epiphysis). This process may also affect the development and appearance of ossification within the longitudinal epiphyseal bracket (delta phalanx). 相似文献
68.
R. Jackisch H. Hotz C. Allgaier G. Hertting 《Naunyn-Schmiedeberg's archives of pharmacology》1994,349(3):250-258
Slices of the rabbit caudate nucleus, preincubated with [3H]dopamine and subjected to electrical field stimulation, were used (1) to investigate the involvement of G-proteins in the signal transduction of presynaptic D2 (auto)receptors and -opioid receptors on dopaminergic axon terminals in this tissue and (2) to study a possible mutual interaction of these two presynaptic receptors. Pretreatment of the slices with either pertussis toxin (8 g/ml; 18 h), or N-ethylmaleimide (30 M, 30 min) significantly reduced the inhibitory effects of both the D2 agonist quinpirole and the -opioid receptor agonist U-50488H on the [3H]overflow evoked by 36 pulses (2 ms, 24 mA, 0.3 Hz), suggesting the coupling of both receptors to G-proteins.Experiments designed to study possible interactions of these two presynaptic receptors were carried out under stimulation conditions (only 1 pulse), which strongly diminish interference of endogenous transmitters released in the tissue with modulatory effects of exogenous drugs. For instance, due to the presence of endogenous dopamine, quinpirole was much less potent during 36-pulse-than during 1-pulse field stimulation, whereas the D2 antagonist domperidone was almost without effect in the latter case. Using the 1-pulse stimulation paradigm, the concentration/response curve of quinpirole was unaffected in the presence of the halfmaximal inhibitory concentration of U-50,488 H (0.1 M). On the other hand, also quinpirole at its halfmaximal inhibitory concentration (0.1 M), hardly affected the concentration/response curve of U-50,488 H: only high concentrations of U-50,488 H (above 1 M) seemed to be slightly less effective in the presence than in the absence of the D2 agonist. U-50,488 H, at these high concentrations, was also less potent under 36-pulse than under 1-pulse stimulation conditions. From these findings, we conclude that there is only a limited interaction between presynaptic D2 autoreceptors and -opioid receptors on dopaminergic axon terminals in the rabbit caudate nucleus, despite they are both coupled to PTX/NEM-sensitive G-proteins.
Correspondence to: R. Jackisch at the above address 相似文献
69.
C. Volz-Zang B. Eckrich P. Jahn B. Schneidrowski B. Schulte D. Palm 《European journal of clinical pharmacology》1994,46(5):399-404
The effects of esmolol at different rates of infusion (100, 250 and 500 g·kg–1 BW·min–1) were compared with -adrenoceptor occupancy (1 and 2, estimated by a subtype selective radioreceptor assay) and plasma concentrations of esmolol and its acid metabolite were measured by HPLC. Up to a rate of infusion of esmolol of 500 g·kg–1 BW·min–1 there was a maximal 1-receptor occupancy of 84.7% while 2-receptor occupancy was below the detection limit; confirming the 1 selectivity of esmolol. Exercise-induced increases in heart rate and systolic blood pressure were reduced by esmolol in a dose-dependent manner. The estimated EC50 values of rate of infusion for the reduction in heart rate and systolic blood pressure during exercise were 113 and 134 g·kg–1 BW · min–1, respectively. Additionally, heart rate and systolic blood pressure were reduced moderately at rest. Because of the short elimination half-life of esmolol caused by the rapid hydrolysis to its acid metabolite, 45 min after end of infusion high plasma concentrations of the metabolite (maximally 80 g·ml–1) but no esmolol were detectable. Since no in vivo effects have been observed, despite the presence of high plasma concentrations of the metabolite, the metabolite did not participate in the observed effects up to an infusion rate of esmolol of 500 g·kg–1 BW·min–1. The plasma concentrations of antagonist detected by radioreceptor assay and plasma concentrations of esmolol detected by HPLC showed a good correlation (r=0.97). Since the cardiovascular effects, determined before and 45 min after termination of infusion of esmolol were similar, it can be concluded that the observed effects on heart rate and systolic blood pressure are exclusively mediated by esmolol.Dedicated to Dr. P.Rajagopal, Kuantan Specialist Hospital, Kuantan, Malaysia 相似文献
70.
Several studies have demonstrated a paradoxical form of antinociception induced by the repeated administration of opioid antagonists accompanied by exposure to a painful stimulus. The underlying mechanism of this naloxone-induced antinociception (NIA) is still unknown, but the results of several studies suggest that it is a non-opioid response. This study was designed to investigate serotonergic and noradrenergic involvement in NIA. Rats were treated daily with systemic injections of 5 mg/kg naloxone, followed by a 45-s hot plate test of nociception (temperature=51.5 ± 0.5°C). After rats reached plateau levels of NIA, they received a test trial in which they were treated with various doses of different selective 5-HT or 2 adrenoceptor antagonists in addition to naloxone before the hot plate test. Rats treated with 0.16, 0.32 and 0.63 mg/kg pirenperone or 2.5 mg/kg ritanserin showed significant reductions in paw lick latency with respect to rats treated with vehicle. In addition, high doses of yohimbine (7.5–10 mg/kg) also effectively reversed NIA. In contrast, NIA was not affected by acute blockade of 5-HT1 or 5-HT3 receptors by methiothepin or MDL 72222, respectively, or by the 2 adrenoceptor blocker idazoxan. None of the 5-HT or 2 adrenoceptor antagonists had any effect on the paw lick latencies of saline-treated rats. A possible role of 5-HT2 receptors in the antinociception induced by opioid receptor blockade is discussed. 相似文献