Enrollment and reporting practices in pediatric general surgical randomized clinical trials: A systematic review and observational analysis

Background

Pediatric surgical randomized clinical trials (RCTs) are labor-intensive and costly. This systematic review investigated patient accrual and estimates of study duration in RCTs by interrogating enrollment and registration practices.

Douleurs neuropathiques et inflammatoires: modèles animaux et rôles fonctionnels des neuropeptides

Résumé  Les douleurs chroniques, d’origine inflammatoire ou neuropathique, s’accompagnent de modifications cellulaires responsables d’une sensibilisation persistante et handicapante. L’étude de ces phénomènes de plasticité nécessite de disposer de modèles animaux fiables. De nombreux modèles existent qui ne font chacun que reproduire certains des sympt?mes douloureux. Leur choix dépend donc des pathologies étudiées. L’apparition de modèles génétiquement modifiés avait fait na?tre de grands espoirs mais les phénotypes apparents de ces animaux se révèlent souvent contradictoires, et difficiles à interpréter. Une composante importante de la plasticité associée à la sensibilisation douloureuse concerne le contenu neurochimique des cellules localisées dans les ganglions rachidiens ou la corne dorsale de la moelle épinière. Cette plasticité neurochimique est illustrée par les variations d’expression de deux neuropeptides, la galanine et la cholécystokinine, ainsi que de leurs récepteurs. Au niveau du premier relais sensoriel, la galanine exercerait un effet essentiellement antinociceptif, à fortes doses, en conditions neuropathiques via son récepteur R1. A l’inverse, la cholécystokinine jouerait un r?le pronociceptif dans les neurones spinaux en s’opposant à l’action des opiacés endogènes via le récepteur CCK2. La connaissance des mécanismes d’action des messagers est nécessaire à l’élaboration de traitements thérapeutiques innovants. Parmi les messagers chimiques impliqués dans la transmission douloureuse, les neuropeptides représentent une cible thérapeutique de choix en raison de leur caractère modulateur et de leur forte plasticité d’expression. Néanmoins, le développement d’analgésiques dérivés d’agonistes ou d’antagonistes de ces peptides nécessite encore de parfaire la connaissance de leurs mécanismes d’action et de leurs interactions et ces progrès requièrent l’utilisation de modèles animaux pertinents.

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Summary  Chronic pain is associated with plastic changes responsible from a persitent sensitization in the spinal cords. The studies of these changes have benefit substantially from the development of experimental animal models. If genetically modified animals have carried a lot of new perspective and hopes, their practical use is difficult due to the important phenotypic variability seen amongst them. However, an important aspect of central sensitization is linked with the changes of expression of neuropeptide such as galanin and cholecystokinin and their receptors. In the dorsal horn, galanin has analgesic effects trough its receptor R1. Conversly, cholecystokinin induces pain via an inhibition of endogenous opio?ds through the CCK2 receptor. Future prospect in analgesic drugs requires a good knowledge about the biochemical cascades involved in the transmission of pain. Amongst these, neuropeptides are good candidate targets because they have a strong analgesic potential, and their expression is highly modulated in persistent pain syndromes. The development of this line of research is still pending on the use of appropriate animal models as well as a better knowledge about their mechanisms.

     

Nonatherosclerotic vascular causes of acute abdominal pain

Background

To examine the epidemiology, treatments, and outcomes of acute symptomatic non-atherosclerotic mesenteric vascular disease.

In vitro antioxidant properties of calcium dobesilate

Summary— Calcium dobesilate, a vascular protective agent, was tested in vitro for its scavenging action against oxygen free radicals. Calcium dobesilate was as potent as rutin to scavenge hydroxyl radicals (IC_W = 1.1 vs 0.7 μM, respectively). It was also able to scavenge superoxide radicals, but with 23 times less potency than rutin (IC₅₀ = 682 vs 30 μM, respectively). Calcium dobesilate significantly reduced platelet activating factor (PAF)-induced chemiluminescence in human PMN cells and lipid peroxidation by oxygen free radicals in human erythrocyte membranes, although these actions required calcium dobesilate concentrations ≥ 50 μM. Finally, in cultured bovine aortic endothelial cells, magnesium dobesilate reduced the increase in cytosolic free calcium induced by hydrogen peroxide and inhibited phenazine methosulfate-induced cell potassium loss. In conclusion, calcium dobesilate was effective in scavenging hydroxyl radicals in vitro, at therapeutically relevant concentrations. Conversely, higher concentrations of the compound were required to scavenge superoxide radicals or to protect the cells against the deleterious effects of intracellular reactive oxygen species. Further studies in vivo are required to determine if these antioxidant properties of calcium dobesilate can play a role in its vascular protective mechanisms.     

自制复合抗肿瘤珊瑚羟基磷灰石人工骨体外抗肿瘤实验

目的:评价自制复合抗肿瘤珊瑚羟基磷灰石人工骨体外抗肿瘤活性。方法:实验于2006-01/12在解放军广州军区广州总医院骨科及南方医科大学基础医学院细胞生物学教研室实验室进行。①将南海澄黄海珊瑚礁块制成的珊瑚碳酸钙通过水热反应转变成珊瑚羟基磷灰石人工骨后,再通过真空冷冻干燥等处理将顺铂载入形成复合抗肿瘤珊瑚羟基磷灰石人工骨,将复合人工骨一部分切开后行电镜扫描及能谱分析,以了解顺铂在人工骨孔隙中的分布及比例。②另精确称取复合人工骨1g浸入避光模拟体液50mL中,37℃,30r/min恒温振荡器中浸泡后,取得不同时间浸提液各10mL,将浸提液过滤除菌分装后再真空冷冻干燥制成粉剂低温保存。③以乳腺癌骨转移原代培养细胞(标本取自广州军区广州总医院手术切除标本)、高转移性肺癌SPCA-1细胞株及前列腺癌骨转移pc-3细胞株(购自中国生命科学院上海细胞所)为实验对象,利用MTT法分别检测对照组(单纯羟基磷灰石浸提液)、复合人工骨2,4,6及8周浸提液的体外抑制肿瘤细胞作用(计算肿瘤细胞的抑制率)。结果:①复合人工骨孔隙内顺铂分布均匀,能谱分析示复合顺铂占人工骨的体质量的10.05%。②复合人工骨2,4,6及8周浸提液体外对乳腺癌细胞的抑制率分别为71.83%,68.34%,63.74%及62.35%;对肺癌细胞的抑制率分别为81.59%,80.14%、74.81%及62.89%;对前列腺癌细胞的抑制率分别为85.04%,84.34%,65.66%及29.92%。除8周浸提液对前列腺癌的抑制率为29.92%为低度敏感外,复合人工骨8周内的浸提液在体外对肿瘤细胞的抑制率均>50%,为高度敏感。结论:自制顺铂珊瑚羟基磷灰石复合人工骨具有良好的缓释功能,其缓释液在8周内可抑制及杀伤肿瘤细胞。     

Nucleic acid hybridization in the diagnosis of viral infections

Recombinant DNA technology, including molecular cloning and nucleic acid hybridization, is now being applied to problems in clinical virology. Although viral isolation in cell culture remains the most sensitive and specific diagnostic test for many viruses, for some viruses, isolation in cell culture is lengthy or difficult or has not yet been achieved. Utilization of hybridization techniques has already resulted in important new information concerning the pathogenesis of a number of viruses, such as Epstein-Barr virus, hepatitis B virus, and human papillomavirus. In addition, time to diagnosis for viruses such as cytomegalovirus, Epstein-Barr virus, and varicella-zoster virus can be significantly shortened to 36 to 48 hours, a great improvement over standard isolation with obvious importance for patient management. Hybridization techniques have also been applied to screening of antiviral agents. Although results of studies to date have been encouraging, significant problems remain to be solved before these techniques can be applied in a routine diagnostic laboratory. First, more sensitive assays must be developed. One approach is the generation of probes with higher specific activities. Synthesis of single-stranded probes using recombinant M13 bacteriophage as a template results in probes of higher specific activities that also cannot re-anneal to themselves because they are not complementary. Thus, more probe is available to anneal to sample DNA. Synthesis of cRNA probes that form more stable hybrids with DNA is another approach that is receiving attention. A second problem is reagent safety and stability. The most sensitive and commonly used label in the studies reviewed in this article has been 32P. With its half-life of 2 weeks, potential hazards to personnel, and disposal problems, it is probably not suitable for clinical laboratories. A major step in the development of nonradioactive, stable probes has been synthesis of biotinylated nucleotide analogues that can be efficiently incorporated into DNA or RNA. Biotinylated probes are stable for 1 to 2 years at -20 degrees C, and their use obviates the need for autoradiography, thus shortening reaction times. In addition, very high concentrations of probes can be used without the background problems encountered with radiolabels. To date, biotinylated probes have been significantly less sensitive than those labeled with 32P, but continued efforts to improve sensitivity have yielded promising results.(ABSTRACT TRUNCATED AT 400 WORDS)