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991.
M. J. Morris M. David-Dufilho M. A. Devynck 《Clinical and experimental pharmacology & physiology》1988,15(4):257-260
1. Altered calcium regulation has been observed in experimental and human hypertension. In this study erythrocyte (RBC) intracellular calcium concentration ([Ca2+]i) was compared in conscious spontaneously hypertensive rats (SHR) and their normotensive controls (WKY) at rest and after injection of the dihydropyridine calcium antagonist PN 200.110. 2. Resting [Ca2+]i was similar in SHR and WKY. 3. PN 200.110 administration induced a rapid decrease in blood pressure in SHR and WKY. Five minutes after the injection no change in [Ca2+]i was observed; at 1 h [Ca2+]i was significantly decreased in SHR, but not in WKY. 4. These results suggest that the mutual adaptation of the rate of calcium influx through calcium channels and the activity of the calcium extruding pump differ between WKY and SHR. 相似文献
992.
H. G. Schaefer R. Heinig G. Ahr H. Adelmann W. Tetzloff J. Kuhlmann 《European journal of clinical pharmacology》1997,51(6):473-480
Objective: Nisoldipine, a calcium antagonist of the dihydropyridine class, has been used in the treatment of hypertension and angina
pectoris. A new controlled-release dosage form (nisoldipine coat-core, NCC) has been developed to allow once daily dosing.
In addition to a formal food interaction study as requested by regulatory authorities for controlled-release dosage forms,
a subsequent study was conducted to determine the clinical relevance of the changes in nisoldipine plasma concentration vs
time profiles seen in the food effect study.
Methods: After a placebo run-in phase of 6 days, 12 hypertensive patients started treatment with 20 mg NCC once daily (days 0–3,
5–6, 8–9). On days 4, 7 and 10 the NCC was substituted for 5, 10 and 20 mg nisoldipine solution, respectively, in order to
obtain nisoldipine plasma concentration vs time profiles comparable to the ones resulting from the concomitant intake of food
and NCC. Simultaneous measurements of blood pressure (BP) and nisoldipine concentration were performed on days 3, 4, 7 and
10.
Results: The relationship between nisoldipine plasma concentrations and percentage reduction in BP [diastolic (DBP) and systolic
(SBP), supine and standing] could be described by an Emax model. The mean maximum reduction (Emax) relative to baseline was about 36.4% and 37.7% (DBP, supine and standing) and 27.9% and 29.2% (SBP, supine and standing),
respectively. The interindividual variability (% CV) in Emax was low, ranging from 17.6% to 28.8%. The mean nisoldipine plasma concentration corresponding to 50% of the maximum effect
(EC50) ranged between 0.99 and 2.62 μg · l–1 with a pronounced interindividual variability (% CV) of 89.5–108.8%. Mean Cmax values after administration of the 30 and 40 mg NCC together with food were 4.5 and 7.5 μg · l–1, respectively. Based on the concentration-effect relationship established in the present study, the effect achieved with
a concentration of 7.5 μg · l–1 will be about 77% of Emax for DBP and about 88% of Emax for SBP, respectively.
Conclusion: At the time of maximum plasma concentration the additional decrease in BP relative to baseline due to the food effect will
be about 7–15% for DBP and 3–9% for SBP. After administration of the 10␣mg solution with a mean Cmax of 8.7 μg · l–1, only headache and flush with mild severity have been reported as adverse events. These maximum concentrations are comparable
to Cmax values seen after intake of 40 mg NCC with food. With regard to heart rate (HR) there were distinct differences between the
two formulations: Following administration of 5, 10 and 20 mg nisoldipine solution, there were dose-dependent increases in
HR by a maximum of 4, 12 and 16 beats · min−1, respectively, whereas the HR profile for the NCC was similar to that seen under placebo treatment.
Received: 28 December 1995 / Accepted in revised form: 19 August 1996 相似文献
993.
通过38例、22-50岁和51-60岁两个年龄组,三种不同麻醉方法,观察了麻醉前、麻醉后和术毕PTH、CT、Ca、P的变化。术华的钙磷值较术前值下降、硬膜外手术下和各观察组中的51~60岁年龄组的钙磷值变化更加明显。说明在麻醉手术应激状态下,病人的中枢神经系统处于抑制状态,植物神经系统的调节受到影响,使PTH、、CT、钙和磷之间的调节反馈关系发生变化。钙磷的平衡受到一定的影响。同时也观察到术中与术毕适量补钙剂后,血钙值能够恢复到术前水平。术中未补钙者,于术后4~5天可恢复到术前水平。 相似文献
994.
BJØORN ÖGAARD GUNNAR RÖLLA TON DIJKMAN JAN RUBEN JOOP ARENDS 《European journal of oral sciences》1991,99(5):372-377
Abstract— Shark enamel consists of nearly pure fluorapatite and has been shown to demineralize in an in situ caries model. The present study was conducted to investigate whether additional fluoride supplementation in the form of mouthrinsing would inhibit lesion development in shark enamel. The study slabs of shark enamel were mounted in dental appliances. Six individuals wore the appliances while rinsing daily with a neutral 0.2% NaF solution for 4 wk. The specimens were analyzed by means of quantitative microradiography, and the data compared with a previous study using untreated shark enamel and the same participants. It was found that fluoride rinsing did not measurably inhibit enamel demineralization in 4 wk. Scanning electron microradiographs showed that calcium fluoride-like material was not formed on shark enamel after neutral fluoride treatment, supporting a previous study. The present study indicates, therefore, that formation of a calcium fluoride-like material on the enamel surface may be essential for the cariostatic effect of topical agents. 相似文献
995.
急性胰腺炎大鼠细胞钙—镁ATP酶的变化及维生素E的影响 总被引:2,自引:0,他引:2
目的:研究急性胰腺炎(AP)大鼠细胞钙-镁ATP酶的变化及维生素E对其的影响,以进一步探讨维生素E在AP治疗中的作用机制。方法:将56只SD大鼠分为正常组、AP组及AP后维生素E治疗组3组,后两组在制备AP动物模型后分别于1、5、10h活体取材胰、肝组织,通过钙-镁ATP酶的酶组织化学染色检测其活性;同时通过逆转录聚合酶链反应(RT-PCR),测定其组织钙-镁ATP酶的表达。结果:实验大鼠胰、肝组织细胞钙-镁ATP酶酶组织化学染色阳性率AP组低于正常组(P<0.05),且AP组5h的阳性率低于1h;维生素E治疗组的阳性率高于AP组(P<0.05)且5h的高于1h。RT-PCR结果显示:胰腺组织钙-镁ATP酶的表达AP组最低,且AP组5h的表达低于1h;维生素E治疗组的钙-镁ATP酶表达高于AP组,且5h的表达高于1h;肝组织钙-镁ATP酶的表达各组均为阳性,各组间无显著性差异。结论:AP时细胞钙-镁ATP酶活性降低,可参与AP时细胞钙超载的发生和发展,由引引起细胞正常结构与功能的破坏,加重AP的病理变化。维生素E通过其抗氧化作用在治疗AP的过程中,提高细胞钙-镁ATP酶活性,减轻细胞钙超载,这可能是其作用机制之一。 相似文献
996.
异紫堇啡碱对血管平滑肌钙内流和钙释放的影响 总被引:12,自引:1,他引:11
目的研究异紫堇啡碱(ISOC)对血管平滑肌钙内流和钙释放的影响,以初步阐明其作用方式。方法利用兔胸主动脉螺旋条标本观察ISOC对去甲肾上腺素(NA)及KCl量效曲线的影响和对无钙液中NA、CaCl2复钙、咖啡因缩血管效应的影响。结果ISOC10μmol·L-1对NA的量效曲线呈非竞争性拮抗作用,而对高钾的作用则不明显。在无钙液中,ISOC100μmol·L-1能明显抑制NA所致的收缩及复钙后外钙内流诱发的收缩,ISOC10及30μmol·L-1则只作用于前者;各实验浓度的ISOC对咖啡因在无钙液中的缩血管作用均无影响。结论ISOC抑制受体中介的钙释放和钙内流,但不是典型的钙拮抗剂。 相似文献
997.
α-Latrotoxin (α-LT) potently enhances quantal release of neurotransmitter from nerve terminals. To develop the adrenal chromaffin cell as a ‘model' system for the study of mechanisms of toxin action, we used amperometry to examine secretion of catecholamines and spectrofluorometry to measure cytosolic Ca. Several key features of toxin action emerged. (1) Release occurs at concentrations of toxin >35 pM and the pattern of release changes from repeated brief bursts to more continuous discharges of varying duration as the toxin concentration increases. (2) Release requires extracellular calcium in the micromolar range, but not the activity of native voltage-dependent calcium channels. (3) Release is associated with a rise in cytosolic calcium to near micromolar range. (4) Provided calcium is later restored, release can be induced even though the toxin is applied and washed away in calcium-free saline. These features largely resemble those of α-LT action on nerve terminals. They suggest that in chromaffin cells, as in neurons, the Ca-dependence of toxin-enhanced quantal release is based on Ca entry through toxin-induced channels rather than a requirement of extracellular Ca for toxin binding. 相似文献
998.
Man Qin Zuyan Zhang Kenshi Maki Mariko Naito Akiko Morimoto Mitsutaka Kimura 《Journal of bone and mineral metabolism》1998,16(2):88-95
To determine whether the mixture of calcium carbonate and calcium citrate, an oral calcium supplement made from sea shell
that is called UNICAL, had any beneficial effect on bone debilitation, we examined the mandibular alveolar bone of pubertal
Wistar male rats by bone mineral mass, Ca/P ratio microanalysis, and scanning electron microscopy. (1) Bone mineral mass of
UNICAL-fed rats in the low-calcium experiment group was not significantly different than the control group, although its value
was significantly higher than in pair-fed standard diet rats. However, although the bone mineral mass of UNICAL diet rats
in the calcium-deficient experiment group was significantly higher than in pair-fed standard diet rats, it was significantly
lower than in the control group. (2) All Ca : P ratio values in experiment groups were significantly lower than that in control
group. Ca : P ratio values of UNICAL diet rats were significantly higher than those of pair-fed standard diet rats in experiment
groups. Separately, Ca : P ratio was not significantly different between UNICAL diet rats of the calcium-deficient experiment
group and standard diet rats of the low-calcium experiment group. (3) On scanning electron microscope observation, UNICAL
diet animals were observed to have more sufficient calcareous microdepositions in bone remodeling areas, which was thought
to be one of the morphological indications of bone formation, reflecting active calcium utilization in bone metabolism, than
pair-fed standard diet animals. These results suggested that the mixture of calcium carbonate and calcium citrate had a positive
effect on bone debilitation to a certain extent in growth-period rats.
Received: Nov. 25, 1997 / Accepted: Jan. 29, 1998 相似文献
999.
谷氨酸诱发培养的大鼠星形胶质细胞内钙升高的机制 总被引:10,自引:0,他引:10
目的 研究谷氨酸对纯化培养的大鼠星形胶质细胞的胞内钙信号的影响及受体作用机制。方法 用显微荧光测量技术监测星形胶质细胞内钙信号的动态变化和谷氨酸对其的影响,观察阻断NMDA和/或AMPA受体,谷氨酸对胞内钙信号影响的变化。结果 谷氨酸明显升高胞内游离钙浓度,NMDA和AMPA受体拮抗剂、胞外钙离子浓度的降低及钙离子螯合剂均可不同程度地减弱其引发的胞内游离钙离子升高程度。结论 谷氨酸通过多种途径影响星形胶质胞内钙信号,激活NMDA和AMPA受体是其中的重要机制之一。 相似文献
1000.
P. Fort A. Khateb A. Pegna M. Mühlethaler B. E. Jones 《The European journal of neuroscience》1995,7(7):1502-1511
The effects of noradrenalin were tested upon electrophysiologically characterized cholinergic nucleus basalis neurons in guinea-pig brain slices. According to their previously established intrinsic membrane properties, the cholinergic cells were distinguished by the presence of low-threshold Ca2+ spikes and transient outward rectification that endowed them with the capacity to fire in low-threshold bursts in addition to a slow tonic discharge. A subset of the electrophysiologically identified cholinergic cells that responded to noradrenalin had been filled with biocytin (or biotinamide) and documented in previously published reports as choline acetyltransferase (ChAT)-immunoreactive. The noradrenalin-responsive, biocytin-filled/ChAT+ cells were mapped in the present study and shown to be distributed within the substantia innominata amongst a large population of ChAT+ cells. Slices from another subset of noradrenalin-responsive, electrophysiologically identified cholinergic cells were stained for dopamine-β-hydroxylase to visualize the innervation of the biocytin-filled neurons by noradrenergic fibres. These biocytin-filled neurons were surrounded by a moderate plexus of varicose noradrenergic fibres and were ostensibly contacted by a small to moderate number of noradrenergic boutons abutting their soma and dendrites. Applied in the bath, noradrenalin produced membrane depolarization and a prolonged tonic spike discharge. This excitatory action was associated with an increase in membrane input resistance, suggesting that it occurred through reduction of a K+ conductance. These effects persisted when synaptic transmission was eliminated (by tetrodotoxin or low Ca2+/high Mg2+) and were therefore clearly postsynaptic. The excitatory effect of noradrenalin was blocked by the α1-adrenergic receptor antagonist prazosin and not by the α2-antagonist yohimbine, and it was mimicked by the α1-agonist L-phenylephrine but not by the α2-agonists clonidine and UK14.304, indicating mediation by an α1-adrenergic receptor. There was also evidence for a contribution by a β-adrenergic receptor to the effect, since the β-antagonist propranolol partially attenuated the effect of noradrenalin, and the β-agonist isoproterenol produced, like noradrenalin, alone or when applied in the presence of the α1-antagonist prazosin, membrane depolarization and an increase in tonic spike discharge. These results indicate that through a predominant action upon α1-adrenergic receptors, but with the additional participation of β-adrenergic receptors, noradrenalin depolarizes and excites cholinergic neurons. This action would tend to drive the cholinergic cells into a tonic mode of firing and to stimulate or increase the rate of repetitive spike discharge for prolonged periods. The noradrenergic locus coeruleus neurons could thereby recruit the cholinergic basalis neurons to act in tandem with them in facilitating cortical activation during wakefulness. 相似文献