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61.
Summary Experiments were carried out to elucidate the mechanism that the positive inotropic effect mediated by 1-adrenoceptors is more susceptible to organic calcium antagonists than the -adrenoceptor-mediated effect. Verapamil and diltiazem displaced the specific binding of [3H]prazosin to the membrane fraction derived from the rabbit ventricular myocardium, verapamil being about 70 times more potent than diltiazem. Nifedipine did not displace the binding. While these compounds suppressed the positive inotropic effect mediated via l-adrenoceptors in 1- concentration-dependent manner, there was no correlation between the potency of the compounds to displace the [3H]prazosin binding and to inhibit the -mediated positive inotropic effect. The relative potency of three calcium antagonists to decrease the basal force of contraction and the al-mediated effect (of the same extent as compared to basal force of contraction) was consistent to each other. The positive inotropic effect mediated by -adrenoceptors was inhibited much less, and was enhanced by low concentrations of organic calcium antagonists. The differential action of calcium antagonists on the - and -mediated positive inotropic effect was mimicked by lowering the extracellular calcium concentration to 1/2, 1/4 and 1/8 of that in normal Krebs-Henseleit solution (2.5 mmol/l). These results indicate that the 1-adrenoceptor blocking activity does not play an essential role for the preferential inhibition of -mediated positive inotropic effect by organic calcium antagonists. Difference in the subcellular mechanism involved in mobilization of intracellular Ca2+ subsequent to 1-and -adrenoceptor activation may be responsible for the differential inhibitory action of calcium antagonists in the rabbit heart.
Send offprint requests to M. Endoh at the above address 相似文献
62.
金银花水煎剂对绿脓杆菌P29株R质粒体内体外消除作用的实验研究 总被引:3,自引:0,他引:3
目的 :探讨金银花对绿脓杆菌 R质粒消除作用。方法 :体外试验 金银花水煎剂亚抑菌浓度作用绿脓杆菌 P2 948h后 ,影印培养 ,计数消除子 ;体内试验 建立肠道去污染小鼠动物模型后 ,经口感染绿脓杆菌 ,同时给金银花水煎剂 ,灌胃给药 ,2 mg/只 ,2 4 h后再次给药 ,剂量同上 ,48h后处死小鼠 ,分离培养细菌 ,计数消除子数。消除子经质粒抽提琼脂糖凝胶电泳鉴定。结果 :金银花水煎剂对绿脓杆菌 P2 9株 R质粒体外消除率为 0 ,体内消除率为 8%。结论 :金银花水煎剂对去污染小鼠感染绿脓杆菌 P2 9株 R质粒具有消除作用 ,消除子主要表现对单一抗生素恢复敏感性 ;体外没有消除 R质粒作用。 相似文献
63.
Fausto Rossini Pietro Pioltelli Silvia Mingozzi Rino Bregani Franco Viganó Silvia Bolis Ivana Casaroli Eraldo Lanzi Enrico M. Pogliani Gianmarco Corneo 《Supportive care in cancer》1994,2(4):259-265
This study aimed to evaluate the efficacy of amikacine and ceftazidime as an empirical antibiotic therapy for neutropenic patients affected by haematological neoplasms and to investigate the presence of prognostic features suggesting a poor outcome with this antibiotic combination at the onset of infection. This could allow the identification of subgroups of patients with a low rate of response to amikacin/ceftazidime therapy; in these patients different initial empirical therapy may be indicated. The study population comprised 166 severely neutropenic (absolute neutrophil count below 500/l) oncohaematological patients with fever or clinical signs of infection. Multivariate analysis confirmed four negative prognostic factors: 3 or more days of hospitalization at the onset of an infectious episode, a diagnosis of acute myeloid leukaemia, a haematological disease status different from complete remission, the presence of pneumonia. Depending on how many factors are present, cases can be stratified into three groups, of significantly different prognosis: favourable (0 or 1 factor) 76% success; intermediate (2 factors) 52% success; unfavourable (3 or 4 factors) 19% success. At the onset of an infectious episode a subgroup of patients with a very low response rate to empirical amikacin/ceftazidime antibiotic therapy is identifiable, for whom a different therapy is indicated. Because of the high rate of proven or probable fungal infections in this group, the immediate administration of a systemic antifungal therapy, in addition to antibacterial agents, could be considered in these high-risk patients. Studies should be specifically addressed to evaluating a stratification of empirical antibiotic therapy according to risk factors present at the onset of infection. 相似文献
64.
Haruyasu Yamaguchi Koji Ishiguro Shiro Sugihara Yoichi Nakazato Takeshi Kawarabayashi Xiaoyan Sun Shunsaku Hirai 《Acta neuropathologica》1994,88(5):413-419
The localization of apolipoprotein E (ApoE) has been examined immunohistochemically in the autopsied brains of middle-aged and old-aged control subjects, with and without amyloid protein (A) deposits, and of Alzheimer's disease patients. Senile plaques were consistently labeled with ApoE antiserum even in the very early stage of senile plaque formation seen in the fifth decade. In the cerebellar molecular layer, small dots of ApoE immunoreactivity, which were prominent in the Alzheimer's disease subjects, were observed in addition to immunoreactivity in diffuse plaques. ApoE antisera labeled all of the extracellular neurofibrillary tangles (NFT), whereas only a small minority of extracellular NFT were positive for A. A punctate pattern of ApoE immunoreactivity was seen at the media of the meningeal vessels lacking amyloid, when senile plaques were present in the nearby cortex. In the early stage of amyloid angiopathy, the distribution of ApoE immunoreactivity was much more extensive than that of A positivity. These findings suggest that ApoE accumulates in the early stage of senile plaque formation and, furthermore, that ApoE accumulation precedes A deposition in extracellular NFT and amyloid angiopathy. 相似文献
65.
F. De Geeter F. R. Franken F. F. Knapp Jr A. Bossuyt 《European journal of nuclear medicine and molecular imaging》1994,21(4):283-291
Contradictory data have been published on the relative behaviour of fatty acids and flow tracers during the subacute stage of myocardial infarction. Therefore, the present study was set up (1) to investigate the potential occurrence of mismatches between -methyl-iodophenyl pentadecanoic acid (BMIPP), a fatty acid analogue, and Sestamibi, and to describe their nature, and (2) to relate these mismatches to clinical characteristics such as whether or not thrombolysis or percutaneous transluminal coronary angioplasty (PTCA) had been performed. Twenty-six patients were studied within 2 weeks after myocardial infarction. Sestamibi and BMIPP single-photon emission tomography (SPET) were performed within 4 days of one another. Activity of both tracers was scored in 16 basal, 16 midventricular and 8 apical segments, using a four-point grading system: 3 = normal (65% of maximum activity), 2 = mildly decreased (45%–64%), 1 = moderately decreased (25%–44%), 0 = severely decreased (0%–24%). Coronary arteriography was obtained during the same hospital stay. Four hundred and seventy-seven segments out of 1040 studied were abnormal for at least one tracer: 197 with higher Sestamibi activity (group I), 226 with equal scores for Sestamibi and BMIPP (group II) and 54 with higher BMIPP activity (group III). Seventy-five percent of group I segments and 84% of group III segments were found in infarct-related artery territories. Group I segments were associated with acute thrombolysis and/or PTCA (P < 0.01), and with the absence of prior infarction in the territory of the infarct-related artery (P < 0.001). Group III segments were associated with the absence of thrombolysis or PTCA (P < 0.001), with occlusion of the infarct-related artery (P < 0.001), with previous infarction in the same territory (P < 0.001) and with a- or dyskinesia in this territory (P < 0.001). These data could support the interpretation that areas in which the uptake of BMIPP is more decreased than that of Sestamibi (group I) are due to delayed recovery of fatty acid metabolism after reperfusion, whereas those with higher BMIPP than Sestamibi activity (group III) are accounted for by the enhanced metabolism induced by passive systolic wall stretch. 相似文献
66.
Anne-Ulrike Trendelenburg Klaus Starke Norbert Limberger 《Naunyn-Schmiedeberg's archives of pharmacology》1994,350(5):473-481
2-Adrenoceptors modulating the release of dopamine were identified and characterized in slices of the head of the rabbit caudate nucleus. Release of endogenous dopamine was measured by fast cyclic voltammetry as the increase in the extracellular concentration of dopamine elicited by electrical stimulation. The electrochemical signal was identified as dopamine by means of the oxidation potential, the voltammogram and the fact that the signal was not changed by desipramine, which inhibits the high affinity uptake of noradrenaline, but was greatly increased by nomifensine, which in addition inhibits the high affinity uptake of dopamine.Stimulation by 6 pulses/100 Hz increased the extracellular concentration of dopamine by about 85 nM. The selective 2-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) reduced this release with an EC50 of 173 nM and by maximally 75%. The 2-adrenoceptor agonists clonidine and oxymetazoline only tended to cause a decrease. Six drugs, including oxymetazoline, were tested as antagonists against UK 14,304. Their order of antagonist potency (pKD values in brackets) was rauwolscine (8.0) > oxymetazoline (7.5) > 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101; 7.3) > phentolamine (7.1) > corynanthine (5.1) prazosin (< 6). Given alone, the antagonists did not change the release of dopamine elicited by 6 pulses/100 Hz, and the same was true for the dopamine receptor antagonist sulpiride. When caudate slices were stimulated by 10 pulses/1 Hz, sulpiride increased the release of dopamine. Desipramine and rauwolscine, in contrast, again caused no change.It is concluded that dopaminergic axons in the rabbit caudate nucleus possess release-inhibiting 2-adrenoceptors. The antagonist affinities indicate that they belong to the 2A subtype. In this, they agree with all presynaptic 2-autoreceptors studied so far in rabbits as well as with the 2-heteroreceptors modulating the release of serotonin in rabbit brain cortex, suggesting that at least the majority of presynaptic 2-adrenoceptors in the rabbit are 2A. The agonist sensitivity of the caudate presynaptic 2-adrenoceptors is low in comparison with cerebrocortical presynaptic 2-autoreceptors, possibly due to absence of a receptor reserve.
Correspondence to: N. Limberger at the above address 相似文献
67.
Carlo Alberto Maggi Peter Holzer Sandro Giuliani 《Naunyn-Schmiedeberg's archives of pharmacology》1994,350(5):529-536
The aim of this study was to compare the stimulus-response characteristics of the cholinergic and tachykininergic excitatory transmission to the circular muscle of the guinea-pig proximal colon and their susceptibility to inhibition by the N-type calcium channel blocker -conotoxin (CTX). All experiments were performed in the presence of guanethidine (3 M), indomethacin (10 M), L-nitroarginine (L-NOARG, 30 M) and apamin (0.1 M). In the presence of the tachykinin receptor antagonists, FK 888 (10 M) and GR 94800 (3 M), to block NK1 and NK2 receptors, respectively, electrical field stimulation (EFS) produced frequency-dependent atropine- (1 M) sensitive contractions. In the presence of atropine (1 M), EFS produced tachykininergic contractions which were abolished by the combined administration of FK 888 (10 M) and GR 94 800 (3 M). The maximal responses produced by cholinergic and tachykininergic neurotransmission ranged between 80 and 100% of the maximal contractile response to 80 mM KCI. The frequency of stimulation, pulse width and voltage required to produce 50% of the maximal cholinergic and tachykininergic contraction were not different from each other, although cholinergic transmission appeared more efficient in producing twitch contractions in response to single pulse EFS. Furthermore, cholinergic transmission was more efficient than tachykininergic transmission in producing contraction in response to short periods of EFS.CTX (0.1 M for 30 min) produced a large and comparable rightward shift of the cholinergic and tachykininergic frequency-response curve (19 and 17 fold increase in the frequency of stimulation producing 50% of the maximal response, respectively) and markedly depressed (51 and 43% inhibition, respectively) the maximal concentrations response. CTX failed to affect the contraction of the colon produced by submaximally effective concentrations of the muscarinic receptor agonist, methacholine (0.1–0.3 M) and those produced by the tachykinin NK1 and NK2 receptor selective agonists [Sar9] substance P sulfone and [\Ala8] neurokinin A (4–10) (1–3 nM).The present findings demonstrate that the cholinergic and tachykininergic components of the excitatory transmission to the circular muscle of the guinea-pig colon are activated at comparable intensities of nerve stimulation and are both inhibited, in a qualitatively and quantitatively comparable manner, by CTX at the prejunctional level. These findings are consistent with the idea that acetylcholine and tachykinins are co-released from the same population of enteric motoneurones which innervate the circular muscle of the colon.
Correspondence to: C. A. Maggi at the above address 相似文献
68.
Using radioligand binding assays and postmortem normal human brain tissue, we obtained equilibrium dissociation constants (Kds) for 17 antidepressants and two of their metabolites at histamine H1, muscarinic, 1-adrenergic, 2-adrenergic, dopamine D2, serotonin 5-HT1A, and serotonin 5-HT2 receptors. Several newer antidepressants were compared with older drugs. In addition, we studied some antimuscarinic, antiparkinson, antihistamine, and neuroleptic compounds at some of these receptors. For the antidepressants, classical tricyclic antidepressants were the most potent drugs at five of the seven receptors (all but 2-adrenergic and 5-HT1A receptors). The chlorophenylpiperazine derivative antidepressants (etoperidone, nefazodone, trazodone) were the most potent antidepressants at 2-adrenergic and 5-HT1A receptors. Of ten antihistamines tested, none was more potent than doxepin at histamine H1 receptors. At muscarinic receptors antidepressants and antihistamines had a range of potencies, which were mostly weaker than those for antimuscarinics. From the in vitro data, we expect adinazolam, bupropion, fluoxetine, sertraline, tomoxetine, and venlafaxine not to block any of these five receptors in vivo. An antidepressant's potency for blocking a specific receptor is predictive of certain side effects and drug-drug interactions. These studies can provide guidelines for the clinician in the choice of antidepressant. 相似文献
69.
70.
T. Yamada K. Miyazaki N. Koshikawa M. Takahashi H. Akatsu T. Yamamoto 《Acta neuropathologica》1995,89(3):199-203
Gelatinase A is an enzyme capable of cleaving soluble -amyloid protein (AP), and may function as an -secretase to produce secretory forms of amyloid precursor protein. We examined gelatinase A immunoreactivity in the brains and posterior roots of neurologically normal, lacunar stroke, Alzheimer disease (AD), amyotrophic lateral sclerosis, progressive supranuclear palsy and myasthenia gravis cases. The gelatinase A antibody stained only microglial cells in the white matter in all the brain tissues. In AD brain, the reactive microglia located in the center of classical senile plaques, as well as in other microglial cells in the gray matter, showed no immunoreactivity. Gelatinase A in white matter microglial cells may play a role in preventing local deposition of AP. In the posterior root, Schwann cells had positive immunoreactivity. As with other metalloproteases, gelatinase A in Schwann cells may play an antiproliferative role. 相似文献