Neurotransmitter release evoked by α-latrotoxin in the smooth muscle of the female pig urethra

Neuronal regulation of smooth muscle tone in the female pig urethra has mainly been studied in vitro using electrical field stimulation (EFS) of nerves. Excitatory control is considered to be exerted by released noradrenaline, whereas inhibitory control is non-adrenergic non-cholinergic (NANC), and mediated by nitric oxide (NO), and an as yet unidentified agent. We investigated the functional and morphological effects of α-latrotoxin (αLTX), a spider neurotoxin believed to cause massive release of vesicle-stored neurotransmitters, on spontaneously developed urethral smooth muscle tone. The effects were compared to those of EFS and high potassium. In the presence of the NO-synthesis inhibitor N^ω-nitro-L-arginine (L-NOARG: 0.3 mM) both αLTX and EFS evoked contractions. After treatment with scopolamine and phentolamine, no contraction was observed, and under these conditions αLTX and EFS induced relaxation. At low frequencies (<12 Hz), the EFS-induced relaxations were rapid, whereas at higher frequencies (>12 Hz), they were biphasic, consisting of a rapid first phase followed by a more long-lasting second phase. L-NOARG abolished the relaxations at low frequencies, as well as the first phase of the biphasic relaxation. The second phase was not affected by treatment with L-NOARG, but 0.1 μM ω-conotoxin GVIA, blocker of N-type voltage-operated calcium- channels (VOCCs), markedly reduced or abolished the response. In the presence of L-NOARG or ω-conotoxin GVIA, the αLTX-induced relaxation was significantly decreased, and the combination of L-NOARG and ω-conotoxin GVIA further reduced or abolished the relaxation. In preparationstreated with tetrodotoxin or scorpion venom, believed to inactivate nerves by acting on sodium channels, αLTX and EFS had no effects. αLTX-induced relaxation was not associated with changes in cyclic GMP or cyclic AMP content. High (80 mM) potassium solution induced a triphasic response of the preparation. A transient relaxation was followed by a restoration of tone, and then by a persistent relaxation. The persistent relaxation was slightly reduced by scorpion venom or L-NOARG, but reduced by 50% by a combination of L-NOARG and ω-conotoxin GVIA. Ultrastructural analysis of the urethral circular smooth muscle layer revealed a moderate amount of nerve profiles supplying the smooth muscle. In control preparations, the nerve profiles contained both small synaptic vesicles and large dense core vesicles. αLTX caused a major loss of both types of vesicle. The present data suggest that αLTX has the ability to release not only adrenergic and cholinergic transmitters, but also NANC mediators of relaxation, including NO, from nerve terminals in the urethra. Received: 13 January 1997 / Accepted: 17 April 1997     

评价酶联免疫检测血清CYFRA21—1对非小细胞肺癌的诊断价值

目的评价检测ＣＹＦＲＡ２１┐１对非小细胞肺癌的诊断价值。方法用ＥＬＩＳＡ法测定７０例肺癌（ＬＣ）其中４７例非小细胞肺癌（ＮＳＣＬＣ），３例小细胞肺癌（ＳＣＬＣ）和２０例未分型肺癌、６４例肺部良性疾病患者及４０例健康人血清ＣＹＦＲＡ２１┐１浓度。试验的诊断性能用相对操作特征（ＲＯＣ）分析法估测之。结果测得全阈诊断准确率（ＯｖｅｒａｌＤｉａｇ┐ｎｏｓｔｉｃＡｃｃｕｒａｃｉｅｓ）ＬＣ为０．７５、ＮＳＣＬＣ为０．７６，ＳＱＣ为０．８３，ＡＤＥ为０．６７和ＳＣＬＣ为０．３８。在相应于特异性为０．９５的界定值３．４７μｇ／Ｌ处，各型的灵敏度分别为ＳＱＣ０．６２，ＬＣ０．５３，ＮＳＣＬＣ０．５１，ＡＤＥ０．４８和ＳＣＬＣ０．００。结论结果显示ＣＹＦＲＡ２１┐１是ＮＳＣＬＣ较灵敏和特异的一个标志物。未观察到ＴＮＭ各期间该标志物的平均水平有明显的差异；然而异常升高水平的患者的比例随病期的进展而显著增加，提示一系列检测ＣＹＦＲＡ２１┐１水平可能有助于监查ＮＳＣＬＣ患者的疗效。     

Modulation of bone loss during calcium insufficiency by controlled dynamic loading

Summary Changes in the midshaft cross-sectional area of the ulna were measured in egg-laying turkeys on a diet insufficient in calcium. Left: right comparisons were used to assess the bone loss over a six-week period due to 1) calcium insufficiency, 2) calcium insufficiency plus disuse, and 3) calcium insufficiency and disuse interrupted by a short daily period of intermittent loading applied from an external device. Calcium insufficiency alone in the intact ulna resulted in a 15% reduction in cross-sectional area. In the functionally deprived bones this loss was increased to 32%. In bones where the disuse was interrupted by a single short daily period of loading, the degree of bone loss was significantly modified (P<0.006) to 25%. No significant difference in the modulating effect of loading was achieved by varying the peak strain from 0.0015 to 0.003, the strain rate from 0.01 to 0.05, or the duration of the single loading period from 100 sec per day to 25 minutes. All the loading regimes employed had been demonstrated to be osteogenic in mature male birds on a diet sufficient in calcium.     

Calcium entry blocker: Treatment in acute pain in cluster headache patients

15 chronic cluster headache patients in whom pain was induced by nitroglycerin received acute intravenous treatment with a calcium entry blocker. At the time of peak pain we noted a sudden decrease after the Verapamil injection. The mechanism by which the calcium entry blocker afforded relief is unlikely to have been vasodilatation in patients whose blood vessels had just been dilated by nitroglycerin. A more probable mechanism is blockade of the release of the pain-inducing neurotransmitters. The vasodilatation phase is not a primary factor in the onset of pain.

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Sommario Sono stati studiati 15 soggetti affetti da Cluster cronica inducendo loro la crisi dolorosa con Trinitrina, trattandoli poi con calcio antagonista (Verapamil) per via endovenosa. Al momento dell'apice del dolore, valutato dal paziente con un analogo visivo, la somministrazione di Verapamil endovena, determina una rapida estinzione del dolore. L'azione efficace del Ca-antagonista non può sicuramente essere rapportata alla vasodilatazione poiché la crisi dolorosa insorge già in una fase di vasodilatazione per l'azione della Trinitina. Il meccanismo d'azione più probabile è il blocco del release di neurotrasmettitori inducenti l'attacco doloroso. Si sottolinea che la vasodilatazione non è il fattore primario dell'induzione del dolore.

     

拜新同及艾克地平对高血压患者血压变异性的影响

目的　观察拜新同 (长效 )及艾克地平 (中效 )两种钙拮抗剂对高血压患者血压变异性的影响。方法　 79例原发性高血压分为 3组 :未用药组 ;拜新同组 (30mg每日 1次口服 ) ;艾克地平组 (2 0mg每日 2次口服 )。用药的第7d做动态血压监测 ,观察血压变异性。结果　与未用药组比较 :艾克地平组血压变异性改变不显著 (P >0 .0 5 ) ;拜新同组的收缩压变异性下降 (P <0 .0 5 ) ,舒张压变异性改变不明显 (P >0 .0 5 )。结论　拜新同可降低原发性高血压患者的收缩压变异性 ,艾克地平不改变血压变异性。     

应用激光扫描共聚焦显微镜观察晶体上皮细胞中的游离钙

目的用钙的荧光指示剂ｆｌｕｏ－３和激光扫描共聚焦显微镜（ｌａｓｅｒｓｃａｎｎｉｎｇｃｏｎｆｏｃａｌｍｉｃｒｏｓｃｏｐｙ，ＬＳＣＭ）观察大白鼠的晶体上皮细胞（ｌｅｎｓｅｐｉｔｈｅｌｉａｌｃｅｌ，ＬＥＣ）中的游离钙。方法ｆｌｕｏ－３着染细胞后，应用ＬＳＣＭ观察细胞内ｆｌｕｏ－３与钙螯合后的荧光分布，最后用钙离子载体Ａ２３１８７和重金属离子Ｍｎ＋＋作校正，将ｆｌｕｏ－３与钙结合显示的荧光强度转换为［Ｃａ＋＋］ｉ值。结果ＬＥＣ中的游离钙主要分布在细胞核中。大白鼠晶体上皮细胞中的［Ｃａ＋＋］ｉ为２５９．７９±４９．２４ｎｍｏｌ／Ｌ。结论ｆｌｕｏ－３与ＬＥＣ孵育后能着染细胞。用ＬＳＣＭ能直观地观察细胞内钙的分布，并能通过校正得到细胞内游离钙的绝对值。这种成熟的方法，为进一步对ＬＥＣ中游离Ｃａ＋＋的研究提供技术准备     

The use of etidronate and calcium versus calcium alone in the treatment of postmenopausal osteopenia: Results of three years of treatment

The purpose of this open, prospective, controlled, randomized trial was to study the effect of intermittent, cyclic etidronate on the bone mass of osteoporotic postmenopausal women with or without fractures. Eligible subjects were asymptomatic women less than 75 years old who had been amenorrhoeic for at least 1 year. Those with secondary osteoporosis were excluded. Subjects also had to be ambulant with a bone mineral density (BMD) of the lumbar spine >1 SD below that of age matched controls (Z-score < –1 SD). Eighty patients were enrolled, of whom 65 were recruited through a screening programme conducted in the practices of two general practitioners. The remaining patients were from other referrals. The subjects were randomized to two groups of 40 women. Treatment regimens were as follows. The etidronate group was treated with etidronate 400 mg once daily for 14 days followed by 76 days of 500 mg of elementary calcium once daily; this cycle was repeated every 3 months. The calcium group took 500 mg of elementary calcium once daily. The groups were not different in age, height, weight, time since menopause, BMD at baseline and prevalent vertebral fractures. In 50 patients (28 in the etidronate group and 22 in the calcium group) no vertebral fractures were present (67%). Sixty-four patients (35 in the etidronate group and 29 in the calcium group) completed the 3 years of the study. In the etidronate group the mean BMD of the lumbar spine, femoral neck, trochanter and Ward's triangle increased by 5.7%, 1.4%, 7.1% and 10.9% from baseline values respectively (p<0.05 at all sites except for the femoral neck). In the calcium group no significant changes from baseline were found at any time point at any site after 3 years, except for the femoral neck, where BMD at 156 weeks decreased significantly by 3% (p<0.003). In 3 patients, all in the calcium group, six new fractures were found. There were no serious adverse effects. We conclude that intermittent, cyclic treatment with etidronate causes a significant increase in the BMD of the lumbar spine and the proximal femur in osteopenic postmenopausal women, and that treatment is safe and has no serious adverse effects.     

人发微量、宏量元素与血压和脑卒中关系的探讨

本研究使用中子活化测定方法分析对比了我国不同地区三个人群头发中微量元素及宏量元素与血压和脑卒中的关系.结果表明发镧、锌、锰、铜及钙、镁含量在人群间有显著性差异.发镧与血压水平呈正相关,而必需微量元素锌、锰与血压呈负相关.提示镧系元素,尤其镧在人发中和体内含量过高可能与血压升高有关,而锌、锰及宏量元素钙、镁、钾可能是预防血压升高及脑卒中的保护因素.     

Effect of ultrafilterable fragments from chondroitinase and protease-treated aggrecan on calcium phosphate precipitation in liposomal suspensions

A liposome-centered endogenous precipitation method was used to investigate the effect of ultrafilterable fragments from the enzymatic digestion of rat chondrosarcoma aggrecan on the formation of insoluble calcium phosphate salts in buffered solutions at pH 7.4 and 22°C. Unlike the intact aggrecan and its major chondroitin sulfate and core protein components, disaccharide units from chondroitinase degradation of the aggrecan and small (<3kg/mol molecular weight) fragments from protease digestion of the core structure were found to be only weakly inhibitory toward mineral formation. Corresponding reductions in Ca²⁺-binding indicate that these fragments were unable to adsorb to active sites on the apatite surface for long enough periods to significantly hinder crystal growth. The data suggest that controlled enzymatic breakdown of aggrecan may be one possible mechanism by which the calcification of growth plate cartilage is allowed to advance in vivo.The commercial materials and equipment identified in this paper do not imply recommendation or endorsement by the National Institute of Standards and Technology nor is the material and equipment necessarily the best available for the purpose.     

钩藤碱对心血管系统部分药理作用研究

探讨钩藤碱对钙离子的拮抗作用以及对脑血流量和氧消耗的作用。方法观察钩藤碱对豚鼠心肌的兴奋性、功能性不应期、正阶梯现象的作用，以及对去甲肾上腺素诱发的兔主动脉条Ⅰ、Ⅱ相收缩的作用，同时观察钩藤碱对小鼠氧消耗和大鼠脑血流量的影响。结果钩藤碱能提高心肌兴奋性，延长功能性不应期，抑制正阶梯现象和兔主动脉条Ⅰ、Ⅱ相收缩；减慢小鼠氧消耗速度，对大鼠脑血流量无影响。结论钩藤碱具有许多钙拮抗剂的共同特点，提示其在抗心律失常方面会有一定作用。