Triterpenoid saponins, new metalloprotease snake venom inhibitors isolated from Pentaclethra macroloba.

We report here the antiproteolytic and antihemorrhagic properties of triterpenoid saponin inhibitors, named macrolobin-A and B, from Pentaclethra macroloba, against Bothrops snake venoms. The inhibitors were able to neutralize the hemorrhagic, fibrin(ogen)olytic, and proteolytic activities of class P-I and P-III metalloproteases isolated from B. neuwiedi and B. jararacussu venoms. Clotting and fibrinogenolytic activities induced by snake venoms and isolated thrombin-like enzymes were partially inhibited. Furthermore, the potential use of these inhibitors to complement antivenom therapy as an alternative treatment and/or used as molecular models for development of new therapeutical agents in the treatment of snake bite envenomations needs to be evaluated in future studies.     

Immunocytochemical distribution of met-enkephalin-Arg6-Gly7-Leu8 in the rat lower brainstem

The distribution of methionine-enkephalin-Arg6-Gly7-Leu8, a unique peptide derived from proenkephalin A in the rat brainstem, was studied immunocytochemically by using a highly specific antiserum to this octapeptide sequence. Immunoreactive perikarya with various shapes and sizes were detected in many regions of the rat brainstem. Dense accumulation of immunoreactive perikarya and fibers was seen in the nuclei associated with special sensory and visceral functions, such as the interpeduncular nucleus, the parabrachial nucleus, the nucleus of the solitary tract, and the nucleus of the spinal tract of the trigeminal nerve. Clusters of methionine-enkephalin-Arg6-Gly7-Leu8-like immunoreactive perikarya and fibers were observed in certain areas considered to play a role in nociception and analgesia, such as the central gray of the midbrain central gray and the raphe magnus nucleus. Some methionine-enkephalin-Arg6-Gly7-Leu8-like immunoreactive perikarya were distributed in the lateral reticular nucleus, the nucleus of the solitary tract, and the raphe magnus nucleus, where monoaminergic neurons were also detected. In addition to the previously reported enkephalinergic cells, we found many methionine-enkephalin-Arg6-Gly7-Leu8 containing neurons; the rostral and caudal linear nucleus of raphe, the median raphe nucleus, entire length of the raphe magnus nucleus, the medial longitudinal fasciculus, the cuneate nucleus, the external cuneate nucleus, the gracile nucleus, and the area postrema. The wide distribution of this octapeptide-like immunoreactivity reflected neurons expressing the preproenkephalin A gene distributed more widely than previously reported and that innervated many regions.     

The participation of adenosine receptors in the adenosine 5''-triphosphate-induced relaxation in the isolated rabbit corpus cavernosum penis

AIM: To investigate the participation of adenosine receptors in the adenosine 5'-triphosphate (ATP)-induced relaxation in the corpus cavernosum penis (CCP) of rabbits. METHODS: The ATP-induced relaxation was assessed on the noradrenaline precontracted CCP of rabbits in the presence and absence of 8-(3-chlorostyryl)caffeine (CSC); an adenosine A(2A) receptor antagonist; alloxazine and MRS1754; adenosine A(2B) receptor antagonists; and ARL67156, an inhibitor of ecto-nucleoside triphosphate diphosphohydrolases. RESULTS: Adenosine and ATP relaxed the noradrenaline precontracted CCP of rabbits in a concentration-dependent manner. The adenosine- and ATP-induced relaxations were suppressed by alloxazine and MRS1754, but not by 8-(3-chlorostyryl)caffeine. ARL67156 potentiated the ATP-induced relaxation but not the adenosine-induced one. MRS1754 suppressed the ATP-induced relaxation potentiated by ARL67156. CONCLUSIONS: The above results suggest that, in the CCP of rabbits, the adenosine receptor mediating adenosine-induced relaxation is of the A(2B) receptor and the ATP directly causes relaxation through the A(2B) receptor on the CCP.     

3种钾通道在哮喘豚鼠气道高反应中的作用

目的：探讨钙激活钾通道（KCa）、延迟整流型钾通道（Kdr）和ATP敏感型钾通道（KATP）在哮喘豚鼠气道高反应中的作用。 方法： 采用离体气管环张力实验，观察加入特异性钾通道阻断剂后，与不加阻断剂相比气管环对组胺反应的量效曲线的差异。 结果： （１）加入KCa阻断剂TEA后，对照组气管环对组胺的反应变化不显著，而哮喘组气管环对10-4mol/L、10-3mol/L组胺的收缩反应均显著低于不加TEA的气管环(P<0.01)，量效曲线明显下移；（2）加入Kdr阻断剂4-AP后，对照组气管环对10-3mol/L组胺的最大收缩反应明显下降(P<0.05)，组胺的量效曲线下移，哮喘组气管环对10-4mol/L、10-3mol/L组胺的收缩反应均低于不加4-AP的气管环(P<0.01)，且下降程度较对照组大（P<0.05），量效曲线明显下移；（3）加入KATP阻断剂glibenclamide后，对照组和哮喘组气管环对组胺的量效曲线与不加glibenclamide的气管环相比变化均无明显差异。 结论： 在豚鼠哮喘模型中，KCa和Kdr活性的降低在气道高反应的发生中起介导作用，KATP作用不明显。     

云南省600例0~5岁儿童维生素A缺乏调查

目的:了解云南省城乡0~5岁儿童维生素A营养状况及影响因素。方法:省、地、县随机整群抽取600例儿童,采用微量荧光光度法检测VitA含量。结果:VitA缺乏发生率16·17%,地、县明显高于省会城市;0岁儿童明显高于其他年龄组;腹泻儿童明显高于正常儿童;VitA缺乏的影响因素:近1周内进食鸡蛋、奶类制品、鱼虾类、肝类、黄绿色蔬菜、鱼肝油等食物有利于维生素A的吸收,急性呼吸道感染、发烧与维生素A缺乏发生率差异不明显。结论:维生素A缺乏发生率城市明显低于农村地、县两级,说明维生素A缺乏防治工作重点在农村,特别是0岁儿童,防治的主要措施是采取合理膳食,均衡营养,控制腹泻流行。     

南山区与某社区常住人口6年恶性肿瘤发病调查

目的：了解某社区常住人口恶性肿瘤平均年发病率是否高于周边人群，重点是白血病平均年发病率。方法：采用回顾性调查法及个案调查表收集该社区1998年6月～2004年9月常住人口中的确诊恶性肿瘤病人22例，将该社区恶性肿瘤平均年发病率与南山区在该时段恶性肿瘤平均的发病率进行比较。结果：1998年6月～2004年9月南山区常住人口恶性肿瘤平均年发病66．1／10万，某社区常住人口恶性肿瘤平均年发病率29．9／10万，两地差异有统计学意义（F=0．0001，P〈0．05）；南山区常住人口白血病平均年发病率2．79／10万，某社区常住人口白血病平均年发病率4．07／10万，两者无统计学意义差异（F=0．467，P〉0．05）。结论：该社区常住人口恶性肿瘤及白血病平均年发病水平低于南山区全区水平。     

Reassessment of the accuracy of traditional sperm characteristics and adenosine triphosphate (ATP) in estimating the fertilizing potential of human semen in vivo

Receiver operating characteristic curves and accuracy parameters were computed for traditional sperm characteristics (concentration, motility, morphology) and the number of peroxidase negative cells, and the concentration of adenosine triphosphate (ATP) in semen from populations of fertile and infertile men, and men who achieved a pregnancy after varicocele treatment. The percentage and concentration per millilitre of spermatozoa with rapid linear progressive motility, and the ATP concentration, provided the best discrimination between fertile and treated fertile from infertile men. The misclassification rate was higher for sperm morphology, total progressive motility and viability, whereas sperm concentration and the total sperm count per ejaculate had the worst discriminating power. The number of peroxidase negative cells per 100 spermatozoa was highly specific in identifying men who achieved pregnancy after varicocele treatment. The lower limit of normality of sperm characteristics was remarkably different between fertile men and men achieving pregnancy after treatment or during infertility work-up.     

Correlation between 5-HT7 receptor affinity and protection against sound-induced seizures in DBA/2J mice

Audiogenic seizures can be induced in DBA/2J mice following intense auditory stimulation. A number of neurotransmitters, including 5-hydroxytryptamine (5-HT), are believed to be involved in mediating this effect since it has been shown previously that depletion of 5-HT or blockade of 5-HT receptors protects DBA/2J mice from these audiogenic seizures. The present study was undertaken to determine whether antagonism of the newly identified 5-HT₇ receptor may protect DBA/2J mice from audiogenic seizures by attempting to correlate in vivo potency of compounds with their affinity at the 5-HT₇ receptor. All compounds used in the correlation were shown to be antagonists at the 5-HT₇ receptor and a statistically significant correlation was observed between 5-HT₇ affinity and doses for half-maximal response (ED₅₀) for protection of DBA/2J mice from sound-induced seizures (r = 0.80; P < 0.05). No significant correlation was observed between in vivo activity and affinity at either 5-HT_1A, 5-HT_2A or 5-HT_2C receptors. It is also unlikely that interactions between the 5-ht₅ receptor will protect DBA/2J mice from audiogenic seizures since metergoline and mesulergine which are both active in this in vivo model have no affinity for the 5-ht₅ receptor. There are similarities between the pharmacology of the 5-HT₇ receptor and that of the 5-HT_1A receptor, however the correlation between the in vivo potency in DBA/2J mice and 5-HT_1A affinity was not significant. Furthermore, the 5-HT_1A receptor antagonist WAY 100135 did not protect DBA/2J mice from audiogenic seizures at doses that antagonise 5-HT_1A receptor-mediated effects in mice. These data suggest that antagonism of 5-HT₇ receptors may protect against audiogenic seizures in DBA/2J mice although a definitive conclusion must await studies with selective 5-HT₇ antagonists. Received: 20 March 1997 / Accepted: 10 August 1997     

A drug interaction study between ticlopidine and cyclosporin in heart transplant recipients

Objectives: Previous uncontrolled studies have suggested an interaction between ticlopidine, a major antiplatelet agent, and cyclosporin in heart- and kidney-transplant recipients. The aims of this study were to examine in a randomised, double-blind fashion, the possible interaction between cyclosporin A and ticlopidine (250 mg per day) and the tolerability of this combination in heart-transplant recipients. Methods: Twenty heart-transplant recipients were randomised into either a treated or a placebo group. Blood samples were drawn for time-course evaluation of cyclosporin blood levels over a period of 12 h, following the morning intake of cyclosporin and, for platelet aggregation studies, before and after 14 days of ticlopidine administration. Twenty four-hour urine samples were collected for 6-β-hydroxycortisol measurements, before and after 14 days of ticlopidine. Results: Although given at half the recommended daily dosage, ticlopidine significantly reduced platelet aggregation. Pharmacokinetic parameters indicate that the bioavailability of cyclosporin A was not significantly modified by ticlopidine. However, one patient in the ticlopidine group was withdrawn because of a major fall in cyclosporin blood level within 3 days of treatment. Urinary excretion of 6-β-hydroxycortisol was augmented after treatment in the ticlopidine group compared with the placebo group, suggesting that induction of drug metabolism might have occurred. Data also show quite a large intra-individual variability in cyclosporin bioavailability in the placebo group, suggesting that poor absorption of the drug formulation and/or poor compliance might have contributed to the decreased cyclosporin blood levels in the patient withdrawn from this study and in previous uncontrolled studies. Conclusion: Cyclosporin bioavailability was not clearly modified by a half dosage of ticlopidine in this study. We, however, recommend closely monitoring cyclosporin blood levels when prescribing ticlopidine. Further studies will be needed with new formulations of cyclosporin or when using the full dosage of ticlopidine. Received: 20 July 1996 / Accepted in revised form: 12 February 1997     

特异性荧光偏振免疫法监测521例肾移植后环孢素A全血浓度3275次

目的通过监测肾移植后病人环孢素A(CsA)全血浓度 ,提出CsA在三联免疫抑制用药方案中的理想治疗窗。方法用特异性荧光偏振免疫法测定CsA全血浓度 ,对521例病人监测3275次 ,按术后时间及临床表现分组比较。结果肾移植后<1 ,、1～3、3～6、6～12个月、1～2和>2年的CsA全血谷浓度的理想治疗窗应分别为250～450、200～400、150～300、100～250、100～200和100～180μg/L。结论CsA全血浓度在上述范围内 ,中毒反应和排异反应明显减少