人体内镭-226含量及分布

本文分析了101例成人骨灰样品和5例成人尸解样品中镭-226和钙的含量。实验范围内,人骨中镭-226含量与年龄及骨中钙含量呈二元线性相关关系。用苏州市人口相应的年龄构成计权的人骨中镭-226含量为(5.99+0.08)×10^-4Bq／g灰。所测各部位骨的骨灰中镭-226含量的差异无显著性意义;不同部位骨的灰化率差异甚大,由尸解样品中镭-226含量估算的人体软组织中镭-226负荷量约占全身负荷量的20%。此外,本文还根据所测骨、肺、肝,胃,小肠、大肠、骨胳肌和皮肤中镭-226含量,对相应受辐射危险的组织进行了剂量估算,并估算了接受镭-226及其短寿命子体所致年剂量后随机性健康效应发生的几率,将随机性建康效应发生的几率与世界癌症发病率最低的国家或地区的相应组织或器官的癌症发病率相比较,发现前者比后者至少低约二个数量级。     

Glutamate-induced calcium signaling in astrocytes

Astrocytes respond to the excitatory neurotransmitter glutamate with dynamic spatio-temporal changes in intracellular calcium [Ca²⁺]_i. Although they share a common wave-like appearance, the different [Ca²⁺]_i changes--an initial spike, sustained elevation, oscillatory intracellular waves, and regenerative intercellular waves--are actually separate and distinct phenomena. These separate components of the astrocytic Ca²⁺ response appear to be generated by two different signal transduction pathways. The metabotropic response evokes an initial spatial Ca²⁺ spike that can propagate rapidly from cell to cell and appears to involve IP₃. The metabotropic response can also produce oscillatory intracellular waves of various amplitudes and frequencies that propagate within cells and are sustained only in the presence of external Ca²⁺. The ionotropic response, however, evokes a sustained elevation in [Ca²⁺]_i associated with receptor-mediated Na⁺ and Ca²⁺ influx, depolarization, and voltage-dependent Ca²⁺ influx. In addition, the ionotropic response can lead to regenerative intercellular waves that propagate smoothly and nondecrementally from cell to cell, possibly involving Na⁺/Ca²⁺ exchange. All these astrocytic [Ca²⁺]_i changes tend to appear wave-like, traveling from region to region as a transient rise in [Ca²⁺]_i. Nevertheless, as our understanding of the cellular events that underlie these [Ca²⁺]_i changes grows, it becomes increasingly clear that glutamate-induced Ca²⁺ signaling is a composite of separate and distinct phenomena, which may be distinguished not based on appearance alone, but rather on their underlying mechanisms. © 1994 Wiley-Liss, Inc.     

Effect of the stable thromboxane derivative, carbocyclic thromboxane A2, on membrane potential of rat myenteric neurones in culture

The effects of carbocyclic thromboxane A(2) (cTXA(2); 10(-6) mol L(-1)) on membrane potential and cytosolic Ca(2+) concentration were measured with the whole-cell patch-clamp or the fura-2 method, respectively, at rat myenteric ganglia. cTXA(2) caused a hyperpolarization of myenteric neurones from -19.3 +/- 2.5 to -29.3 +/- 2.3 mV. In addition, the eicosanoid potentiated the carbachol-induced depolarization from 4.2 +/- 1.0 mV under control conditions to 11.1 +/- 1.1 mV in the presence of the cTXA(2) (n = 9). The hyperpolarization was abolished by internal application of CsCl (140 mmol L(-1)), a non-selective blocker of K(+) channels, or EGTA (11 mmol L(-1)in the pipette solution), a chelator of intracellular Ca(2+). A similar inhibition was observed in the presence of charybdotoxin (10(-7) mol L(-1)). Fura-2 imaging experiments revealed a cTXA(2)-evoked increase in the intracellular Ca(2+) concentration as indicated by a rise in the fura-2 ratio signal. This response was mediated by a release of Ca(2+) from intracellular stores as sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase blockade with cyclopiazonic acid (5 x 10(-5) mol L(-1)) completely abolished the response to cTXA(2). A similar inhibition was observed after blockade of phospholipase C with U-73122 (10(-5) mol L(-1)). These results suggest an activation of Ca(2+)-activated K(+) channels by cTXA(2) after stimulation of phospholipase C.     

Protective Effect of Tetrandrine against Excitatory Amino Acids induced Neuronal Injury in Cortical Culture

兴奋性氨基酸类神经毒剂与粉防己碱（ｔｅｔｒａｎｄｒｉｎｅ，Ｔｅｔ）共同作用于原代培养胎鼠大脑皮层神经元２４小时，发现１０７，１０６ｍｏｌ·Ｌ１Ｔｅｔ明显降低５０μｍｏｌ·Ｌ１谷氨酸（ｇｌｕｔａｍａｔｅ，Ｇｌｕ），３００μｍｏｌ·Ｌ１βＮｍｅｔｈｙｌａｍｉｎｏＬａｌａｎｉｎｅ（ＢＭＡＡ，ＮＭＤＡ受体激动剂）和２０μｍｏｌ·Ｌ１βＮｏｘａｌｙｌａｍｉｎｏＬａｌａｎｉｎｅ（ＢＯＡＡ，ｎｏｎＮＭＤＡ受体激动剂）导致的培养液乳酸脱氢酶（ｌａｃｔａｔｅｄｅｈｙｄｒｏｇｅｎａｓｅ，ＬＤＨ）活性的增高；细胞形态损害减轻，细胞数量增加。对２０μｍｏｌ·Ｌ１ＮＭＤＡ介导的神经元损伤改变无影响。提示Ｔｅｔ对某些Ｇｌｕ类神经毒剂引起的胎鼠大脑皮层神经元损伤有一定保护作用，其机制可能是抑制细胞膜上的Ｎａ＋通道开放，阻止膜去极化而影响电压依赖性Ｃａ２＋通道启动。对ＮＭＤＡ受体可能亦有一定作用。     

Pharmacology of KB‐R7943: A Na+–Ca2+ exchange inhibitor

The Na⁺–Ca²⁺ exchange (NCX) system plays a pivotal role in regulating intracellular Ca²⁺ concentration in cardiomyocytes, neuronal cells, kidney and a variety of other cells. It performs a particularly important function in regulating cardiac contractility and electrical activity. One of the leading NCX inhibitors is KB‐R9743 (KBR) that appears to exhibit selectivity for Ca²⁺‐influx‐mode NCX activity (reverse mode of NCX). In this article we reviewed pharmacology of KBR and provide a brief summary of studies with other NCX inhibitors, such as SEA0400 (SEA) and SN‐6 (SN). Potential clinical usefulness of KBR and other NCX inhibitors is still controversial but the reviewed findings may be helpful in designing more selective and clinically useful NCX inhibitors for the treatment of cardiac, neuronal and kidney diseases.     

Ca antagonist ameliorates glomerular injury via suppression of glomerular hypertrophy in spontaneously hypertensive rats

Summary: A study was conducted to determine whether calcium blockers (CCB) have renoprotective effects, and if so to elucidate the mechanisms of such effects.
A total of 30 uninephrectomized (UNX) spontaneously hypertensive rats (SHR), 5 weeks of age, were divided into three groups. Group 1 was fed a diet containing 0.01% manidipine and 8% NaCl, while groups 2 and 3 were fed diets containing only 8 and 0.5% NaCl, respectively. Feeding of these diets began 7 days after UNX (experimental day 0). Bodyweight, urinary protein /24 h, urinary sodium excretion/24 h, and food intake were measured at certain time intervals.
At time of death (day 9 or 21), estimations of inulin clearance (Cin) and morphological evaluations, determination of glomerular sclerosis index (GSI), tubulointerstitial index (TII) and glomerular volume were performed.
Urinary protein was significantly higher in groups 1 and 2 than in group 3 from day 7 onward, but did not differ between the former two groups. Cin in group 2 was higher than in groups 1 and 3 on day 9, but declined to lower levels than in groups 1 and 3 by day 21. There was no difference in Cin between group 1 and group 3 on day 21. Morphometry (GSI and TII) revealed that renal lesions were more progressive in group 2 than in group 1. Glomeruli in group 2 were markedly larger than those in group 1, but no difference in glomerular volume was noted between groups 1 and 3.
Our findings suggest that CCB prevent progression of renal injury induced by accelerated hypertension in UNX SHR. the mechanisms of prevention may, at least in part, be related to suppression of glomerular hypertrophy. Inhibition of renal injury can be achieved without significant reduction of proteinuria.     

心肌缺血再灌注损伤时细胞核被膜钙泵活性特征的研究

目的　研究心肌缺血再灌注损伤时Ca2 + 、ATP、ADP和AMP对细胞核被膜钙泵 (Ca2 + ATPase)活性的调节。方法　采用大鼠心肌缺血再灌注模型 ,密度梯度分离纯化细胞核 ,定磷法测定Ca2 + ATPase活性。结果　与正常大鼠相比 ,缺血再灌注损伤动物血浆MDA和FFA显著升高 (P <0 0 1) ;细胞核Ca2 + ATPase活性下降 ,对Ca2 + 亲和力降低 ;ADP、AMP对核Ca2 + ATPase活性的影响明显减弱 ;ATP对Ca2 + ATPase的作用在 [ATP]小于 1 0mmol L时 ,与正常细胞Ca2 + AT Pase活性无显著差异 ,浓度增至 2 0mmol L时 ,活性低于正常细胞 ,ATP浓度继续增加 ,核Ca2 + ATPase活性快速增加。结论　心肌缺血再灌注损伤时Ca2 + 、ATP、ADP、AMP对心肌细胞核Ca2 + ATPase活性的影响发生了明显改变 ,其病理生理意义值得进一步探讨。     

Accentuated antagonism by angiotensin II on guinea-pig cardiac L-type Ca-currents enhanced by β-adrenergic stimulation

 To examine mechanism(s) underlying the accentuated antagonism by angiotensin II (A-II) on twitch tension, we recorded L-type Ca²⁺ currents (I _Ca,L) using conventional patch-clamp techniques in single, guinea-pig, ventricular myocytes. I _Ca,L was recorded by a step-pulse protocol after eliminating K⁺ conductances (internal Cs⁺ plus tetraethylammonium chloride and K⁺-free extracellular solution). A-II (100 nM) did not affect basal I _Ca,L, but inhibited I _Ca,L that had been enhanced (approximately 200% of control) by (ISO, isoproterenol 100 nM). The inhibitory action of A-II was concentration dependent (concentration eliciting 50% inhibition 88±9 pM, n=41) and the ISO-enhanced component of I _Ca,L was completely blocked by A-II at concentrations above 10 nM. CV-11974 (500 nM), an A-II type-1 receptor (AT₁) antagonist, prevented the inhibitory action of A-II. Pre-incubation with pertussis toxin (PTX) abolished the inhibitory effect of A-II. A-II also inhibited the I _Ca,L enhanced by histamine (500 nM) and forskolin (1 μM), but failed to affect I _Ca,L enhanced by intracellular cyclic adenosine monophosphate (1 mM). The inhibitory action of A-II may therefore involve AT₁ receptors/PTX-sensitive, guanine nucleotide-binding (G) proteins (Gi)/adenylate cyclase and partially explains the A-II-dependent accentuated antagonism of inotropy.     

Ginkgo biloba Extract (EGb 761) Pretreatment Limits Free Radical Oxidative Stress in Patients Undergoing Coronary Bypass Surgery

A growing body of evidence supports the trigger role of free radicals in the delayed functional and metabolic myocardial recovery following cardiopulmonary bypass (CPB) in humans, thus opening the field to specific therapies. This clinical study was designed to evaluate, in 15 patients undergoing aortic valve replacement, whether the extent of CPB- and reperfusion-induced lipid peroxidation, ascorbate depletion, tissue necrosis, and cardiac dysfunction is reduced by orally administered EGb 761, a Ginkgo biloba extract withpotent in vitro antiradical properties. Patients received either EGb 761 (Tanakan, 320 mg/day, n = 8) or a matching placebo (n = 7) for 5 days before surgical intervention. Plasma samples were obtained from the peripheral circulation and the coronary sinus at crucial stages of the operation (i.e., before incision, during ischemia, and within the first 30 minutes post-unclamping), and up to 8 days postoperatively. Upon aortic unclamping, EGb 761 inhibited the transcardiac release of thiobarbituric acid species (p ` 0.05), as assessed by high-performance liquid chromatography, and attenuated the early (5–10 minute) decrease in dimethylsulfoxide/ascorbyl free radical levels, an electron spin resonance index of the plasma ascorbate pool (p ` 0.05). EGb 761 also significantly reduced the more delayed leakage of myoglobin (p = 0.007) and had an almost significant effect on ventricular myosin leakage (p = 0.053, 6 days postoperatively). The clinical outcome of recovery of treated patients was improved, but not significantly, compared with untreated patients. Our results demonstrate the usefulness of adjuvant EGb 761 therapy in limiting oxidative stress in cardiovascular surgery and suggest the possible role of highly bioavailable terpene constituents of the drug.