ReProComet: a new in vitro method to assess DNA damage in mammalian sperm.

The increasing request of chemical safety assessment demands for the validation of alternative methods to reduce the resort to animal experimentation. Methods that evaluate reproductive toxicity are among those requiring the largest use of animals. Presently, no validated in vitro alternative exists for the assessment of reproductive toxicity. Mammalian sperm are sensitive targets of DNA-reactive chemicals, which form premutagenic adducts. Here, we propose a new method based on comet assay to detect DNA damage induced by potential germ cell mutagens in bull sperm available from assisted reproduction practices. In somatic cells, chemical-induced adducts can be revealed by comet assay that detects DNA breaks produced during adduct repair. Mature sperm, however, are devoid of repair enzymes, and adducts are processed only after fertilization. For this reason, comet assay is not sensitive to detect DNA lesions induced in sperm by most chemicals. To overcome such limitation, we developed a modified comet assay based on the addition of a protein extract from HeLa cells to agarose-embedded sperm on microscopic slides. To test the method, sperm were treated in vitro with methyl methanesulfonate (MMS) or melphalan (MLP) and comet assay was conducted both with and without protein supplementation. No effect of MMS or MLP was detected without protein supplementation; on the contrary, a clear-cut dose-dependent effect was measured after addition of the cell extract. These results represent a proof of concept of a novel in vitro mutagenicity test on sperm that could offer a promising approach to complement previously validated in vivo germ cell genotoxicity assays.     

随机系统的最小熵控制

本文放弃传统的MSE准则,从信息论观点出发,发展了随机系统的一种最小熵(ME)控制方法,并从ME控制的等价性、控制限度、存在性、唯一性及必要条件等方面,研究了ME控制的合理性和实用性。ME方法是一种全局分析法,它不仅包含了MSE和MAP准则,且由于全文在整个推导中并未假定高斯性、线性和非时变等,因而原则上适用于诸如非高斯、非线性、时变等传统方法难以处理的复杂系统;不仅适用于工程系统,将其推广到决策、社会、经济等领域会更为自然和切合实际。     

术后镇痛10年后的质量控制探讨：1168例回顾性研究

目的 了解术后镇痛的现状，探讨术后镇痛的质量控制问题。方法 回顾近3个月1168例术后镇痛所采用的镇痛方法和预防术后恶心呕吐的方法，了解镇痛效果和副作用的发生情况，并分析影响镇痛效果和副作用发生率的有关因素，患者的满意度情况。结果 90％采用了连续硬膜外镇痛法，配方主要是小剂量吗啡复合低浓度布比卡因或罗比卡因，静脉镇痛主要采用吗啡复合氯诺昔康。预防术后恶心呕吐（PONV）的方法有5-HT3受体拮抗剂（昂丹司琼或阿扎司琼），氟哌啶，地塞米松等，单用或复合应用。连续硬膜外镇痛需要补救镇痛者约5％，静脉镇痛补救镇痛者约10％。PONV总体发生率低，妇科开腹手术低至20％，女性非妇科手术低至10％，剖宫产术低至1％，使用氟哌啶使妇科手术PONV降低约50％。1例高龄患者出现血氧饱和度下降至82％，经停药、吸氧等处理好转。硬膜外导管脱落0．5％。瘙痒、头晕等并发症小于5％。通过补救镇痛，及时处理并发症，患者满意度在90％以上。结论 硬膜外镇痛方法效果优于静脉镇痛方法，适度镇痛，减少镇痛药量，增加安全性，重视PONV的预防，及时处理镇痛不足和副作用，从而提高患者的满意度，是术后镇痛质量控制的可行的理念和方法。     

停止尿床年龄与青少年自杀行为的关系

目的探讨停止尿床年龄与青少年自杀行为的关系。方法对1920名11岁～16岁的青少年进行调查,由父母完成包括青少年生长发育史、自杀行为、抑郁症状、攻击行为及家庭环境等定式问卷。结果在控制一系列儿童及家庭情况变量后,多变量Logistic回归模型显示3岁后停止尿床与青少年自杀行为的危险性增加显著相关,停止尿床年龄与青少年自杀行为之间存在量效关系（3岁～4岁停止尿床OR值为2.1,5岁及以上停止尿床OR值为3.6）。中介变量分析显示,停止尿床时间晚对自杀行为的效应,至少部分通过抑郁及攻击行为中介。结论停止尿床时间晚可能是青少年自杀行为的早期神经发育预测因素,应进一步探讨青少年自杀行为的早期神经发育危险因素及潜在机制。     

Guidelines for Trials of Behavioral Treatments for Recurrent Headache, First Edition: American Headache Society Behavioral Clinical Trials Workgroup

Guidelines for design of clinical trials evaluating behavioral headache treatments were developed to facilitate production of quality research evaluating behavioral therapies for management of primary headache disorders. These guidelines were produced by a Workgroup of headache researchers under auspices of the American Headache Society. The guidelines are complementary to and modeled after guidelines for pharmacological trials published by the International Headache Society, but they address methodologic considerations unique to behavioral and other nonpharmacological treatments. Explicit guidelines for evaluating behavioral headache therapies are needed as the optimal methodology for behavioral (and other nonpharmacologic) trials necessarily differs from the preferred methodology for drug trials. In addition, trials comparing and integrating drug and behavioral therapies present methodological challenges not addressed by guidelines for pharmacologic research. These guidelines address patient selection, trial design for behavioral treatments and for comparisons across multiple treatment modalities (eg, behavioral vs pharmacologic), evaluation of results, and research ethics. Although developed specifically for behavioral therapies, the guidelines may apply to the design of clinical trials evaluating many forms of nonpharmacologic therapies for headache.     

葡立胶囊与抗骨增生胶囊联用治疗颈椎病的临床研究

目的 了解、观察葡立胶囊与抗骨增生胶囊联用治疗颈椎病对血清SOD含量及疼痛功能评分的影响。方法 对一组神经根型颈椎病患者，用葡立胶囊与抗骨增生胶囊联合应用治疗3个月，测定血清SOD含量及疼痛功能评分变化。结果 颈椎病患者治疗组血清SOD含量与治疗前相比明显升高，疼痛功能评分治疗前相比明显降低。结论 葡立胶囊与抗骨增生胶囊联合应用可明显缓解症状，提高血清SOD活力，延缓颈椎间盘退变，对治疗颈椎病有明显疗效。     

Exo-focal postischemic neuronal damage in the rat brain: alteration of [H]forskolin binding using in vitro autoradiography

We studied the alteration of intracellular signal transduction using quantitative autoradiography of the second messenger system in order to clarify the mechanisms of delayed neuronal damage in the remote areas of rat brain after transient focal ischemia. Chronological changes of [³H]forskolin binding sites were measured to demonstrate the striatal-nigral pathway after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by 3 h, 6 h, 1 day, 3 days, 1 week, 2 weeks and 4 weeks of recirculation. [³H]Forskolin binding sites were found to be markedly decreased in the lateral segment of the caudate putamen supplied by the occluded MCA after 90 min of ischemia with no recirculation. On the contrary, there was no alteration on day 1, but 3 days after ischemic insult, marked reduction of [³H]forskolin binding sites was observed in the ipsilateral substantia nigra which lay outside the ischemic areas. This postischemic delayed phenomenon observed in the substantia nigra developed concurrently with ⁴⁵Ca accumulation, which was detected there in our previous study. The delayed reduction of [³H]forskolin binding sites in the substantia nigra observed in the present study indicates that striatonigral terminal degeneration at presynaptic sites is caused by precedent ischemic damage of the ipsilateral caudate putamen and that exo-focal postischemic neuronal death is caused by a transsynaptic process associated with the ischemic foci.     

Fusimotor reflexes to antagonistic muscles simultaneously assessed by multi-afferent recordings from muscle spindle afferents

Several single agonist/antagonist primary muscle spindle afferents were simultaneously recorded in chloralose anaesthetized cats. It was shown that their dynamic and static sensitivity to sinusoidal muscle stretches could be increased or decreased via the fusimotor system by extension and flexion of the contralateral hind limb as well as by stretch of ipsilateral muscles and stimulation of ipsilateral skin nerves. The results seem to support the hypothesis that the primary muscle spindle afferents convey complex multisensory messages to the central nervous system (CNS).     

Extensive pectoral muscle necrosis after defibrillation: nonthermal skeletal muscle damage caused by electroporation

A 37-year-old Italian male developed a myocardial infarct with subsequent ventricular fibrillation. He was defibrillated seven times with up to 360 Joules. Thirteen days later the patient died of recurrent myocardial infarct due to thrombotic occlusion of the left circumflex coronary artery. At autopsy, necrosis of the right pectoralis muscle was observed. Electroporation is the pathogenetic mechanism of skeletal muscle damage due to multiple defibrillations with high energy levels. Received: 8 January 1998 Accepted: 15 April 1998     

ITERATIVE DYNAMIC PROGRAMMING FOR MINIMUM ENERGY CONTROL PROBLEMS WITH TIME DELAY

This paper presents the use of iterative dynamic programming employing exact penalty functions for minimum energy control problems. We show that exact continuously non-differentiable penalty functions are superior to continuously differentiable penalty functions in terms of satisfying final state constraints. We also demonstrate that the choice of an appropriate penalty function factor depends on the relative size of the time delay with respect to the final time and on the expected value of the energy consumption. A quadratic approximation (QA) of the delayed variables is much better than a linear approximation (LA) of the same for relatively large time delays. The QA improves the rate of convergence and avoids the formation of ‘kinks‘. A more general way of selecting appropriate penalty function factors is given and the results obtained using four illustrative examples of varying complexity corroborate the efficacy of the method.