5-羟色胺受体拮抗剂预防丙泊酚注射痛有效性和安全性的Meta分析

目的系统评价5-羟色胺（5-HT3）受体拈抗剂预防丙泊酚注射痛的有效性和安全性。方法计算机检索PubMed、EMbase、TheCochraneLibrary（2012年第1期）、CNKI、CBM、VIP和WanFangData,查找有关5-HT3受体拈抗剂预防丙泊酚注射痛的随机对照试验（RCT）,检索时限均从建库至2012年9月。由2位研究人员按照纳入和排除标准独立筛选文献、提取资料和评价质量后,然后采用RevMan5．2软件进行Meta分析。结果最终纳入15个RCT,共l413例患者。Meta分析结果显示：①5-HT,组丙泊酚注射痛发生率明显小于对照组[RR=0．14,95％CI（0．09,0．21）,P〈0．00001];②在疼痛程度方面,两组轻度注射痛差异无统计学意义[RR=0．84,95％CI（0．56,1．26）,P=0．39];5-HT,组丙泊酚中度注射痛[RR=0．25,95％CI（0．19,0．34）,P〈0．00001]和重度注射痛的发生率[RR=0．16,95％CI（0．10,0．24）,P〈0．00001]均明显低于对照组。③在术后不良反应方面,5-HT3组术后恶心和呕吐fRR：0．19,95％CI（0．11,0．34）,P〈0．00001]及寒颤[RR=0．20,95％CI（0．12,0．33）,P〈0．00001]的发生率均明显少于对照组。结论5-HT3受体拮抗剂能有效预防丙泊酚注射痛,且能减轻丙泊酚注射的疼痛程度和术后不良反应发生率。受纳入研究的数量和质量限制,上述结论尚待开展更多高质量研究加以验证。     

促性腺激素释放激素拮抗剂在防治卵巢过度刺激综合征中的应用

目的探讨促性腺激素释放激素（GnRH）拮抗剂在预防和治疗体外受精-胚胎移植（IVF-ET）过程中并发卵巢过度刺激综合征（OHSS）的作用。方法选择我院生殖医学中心2011年1月至2013年6月接受IVF-ET助孕,HCG日血清雌二醇（E2）〉4000pg／ml且获卵数〉／20个而取消新鲜胚胎移植的患者44例,随机分为2组。对照组（n=23）予临床常规处理;拮抗剂组（n=21）在此基础上加用醋酸西曲瑞克0．25mg,每日一次,共7d。检测血清E2水平,计算OHSS、中重度OHSS的发生率。结果两组血清E2水平均逐步下降,而拮抗剂组治疗后第3、5、7天血清E2水平均低于对照组（P〈0．05）;拮抗剂组未出现OHSS的比例显著高于对照组（42．9％VS．13．0％,P=0．027）,而中重度OHSS的发生率明显低于对照组（23．8％VS．69．6％,P=0．001）。结论GnRH拮抗剂可以降低OHSS的发生比率、减少轻度向中重度OHSS发展。GnRH拮抗剂是预防和治疗IVF-ET中OHSS的有效措施之一。     

卡维地洛改善腹主动脉缩窄术后大鼠左室肥厚的实验研究

目的　对照观察卡维地洛 (CAR)等药物干预对压力负荷性左室心肌胶原结合蛋白 (Acollagen bindingprotein ,Colligin)和肌凝蛋白同工酶 (α β MHC)表达的影响 ,探讨卡维地洛改善左室重塑的机制。 方法　将腹主动脉缩窄术 (CAB)后 4周的雄性Wistar大鼠分为CAR、美托洛尔 (MET)、和特拉唑嗪 (TER)干预组与CAB组 ,12周后对有关指标进行检测。结果　术后 16周大鼠左室明显肥厚 ,α MHC β MHCmRNA的比值下降 ,ColliginmRNA表达及CollagenⅠ和Colligin蛋白含量增加 (P <0 .0 5 ) ;卡维地洛能够明显改善左室肥厚 ,美托洛尔次之 ,而特拉唑嗪作用不明显 ;CAR组大鼠左室心肌CollagenⅠ和Colligin蛋白的表达下降 ,α MHC β MHCmRNA表达比值增加 ,ColliginmRNA表达下调 (P <0 .0 5 ) ,但MET组和TER组无显著变化 (P >0 0 5 )。结论　卡维地洛下调心肌细胞外基质蛋白和逆转肌凝蛋白同工酶转换的作用可能与其肾上腺素受体阻滞无关 ,可能部分地与其抗增殖作用可能有关 ,是改善左室重塑和治疗心力衰竭的一个新机制     

Ontogeny of androgen receptor expression in the ovine fetal central nervous system and pituitary

In fetal sheep, circulating androgens influence fetal stress responsiveness and the timing of parturition. Nevertheless, little is known about the presence and development of androgen receptors (ARs) in the fetal brain. The present study was undertaken to test the hypothesis that expression of androgen receptor occurs in fetal brain and pituitary, and that the abundance of the AR is ontogenetically regulated. We isolated mRNA from pituitary, hypothalamus, hippocampus, and brainstem in fetal sheep that were 80, 100, 120, 130, and 145-day gestation, and 1 and 7 days postnatal (n=4-5 per group). Using real-time RT-PCR, we measured mRNA expression levels of the receptor in these brain regions and pituitary. In a separate study, we isolated protein from the same brain regions in fetal sheep that were 80 (n=3), 120 (n=4), and 145 (n=4) days. AR mRNA expression in hypothalamus increased in late gestation, starting at 145 days, and increasing progressively after birth. A trend of increasing AR protein in hypothalamus was not significant. AR mRNA expression in pituitary was elevated after 80 days gestation, but with no further increases or decreases in late gestation, while AR protein increased significantly at the end of gestation. In hippocampus and brainstem AR mRNA was constant throughout the latter half of gestation, and AR protein was below the sensitivity of our Western blot assay. We conclude that the fetal brain and pituitary are target sites for circulating androgens or androgen precursors in fetal plasma, and we speculate that the increase in hypothalamic action of androgens immediately prior to birth might be integral to the timing of parturition.     

A 12-week placebo-controlled study of rupatadine 10 mg once daily compared with cetirizine 10 mg once daily, in the treatment of persistent allergic rhinitis

Background:  With the current increasing incidence of allergies worldwide, new treatments showing efficacy and long term safety are needed for chronic conditions such as persistent allergic rhinitis (PER). New generation H1-antihistamines have demonstrated anti-allergic properties, which could possibly enhance their effectiveness in long-term periods of treatment.
Objective:  To investigate the efficacy of rupatadine, in controlling symptoms of PER over a 12-week period.
Methods:  A randomized, double blind, parallel-group, placebo-controlled study was carried out in patients aged older than 12 years with PER. Main inclusion criteria were: instantaneous total symptom score (i6TSS) ≥45, nasal obstruction score ≤12, and overall assessment of PER ≥2 as moderate during the first visit. The primary efficacy endpoint was the 12-week average change from baseline of the patients' i6TSS.
Results:  In all, 736 patients were selected. Of them, 543 (73.8%) were randomized in three different groups: placebo ( n  = 185), cetirizine ( n  = 175) and rupatadine ( n  = 183). Rupatadine ( P  = 0.008) but not cetirizine ( P  = 0.07) statistically reduced the baseline i6TSS vs placebo (47.8%, 44.7% and 38.8%, respectively), after 12 weeks. Onset of action was observed at the first 24 h for both treatments (rupatadine vs placebo, P  = 0.013; cetirizine vs placebo, P  = 0.015). Furthermore, instantaneous total nasal symptoms score (iTNSS) (including nasal blockage) mean change from baseline showed a significant reduction with rupatadine 10 mg in comparison with placebo, along all treatment duration of 12 weeks. Study treatments were well tolerated.
Conclusion:  Rupatadine significantly relieves symptoms of PER, providing a rapid onset of action and maintains its effects over a long period of 12-weeks.     

Interleukin 1 receptor antagonist gene polymorphisms are not risk factors for recurrent pregnancy loss: evaluation of couples

PROBLEM: The interleukin-1 system has been implicated in pregnancy outcome. Fetal carriage of interleukin-1 receptor antagonist (IL-1Ra) specific alleles has been associated with adverse pregnancy outcomes including spontaneous abortion and pre-term labor. This study was undertaken to compare the frequency of IL-1RN 2 alleles among both male and female partners of couples experiencing recurrent pregnancy loss with that of fertile control couples. METHOD OF STUDY: Buccal swabs were obtained from 42 couples experiencing recurrent pregnancy loss and from 20 fertile control couples. DNA was extracted from the buccal swabs and analyzed for the presence of IL-1RN variable number tandem repeat. RESULTS: No significant differences were found when the frequency of IL-1RN 2 polymorphisms were compared between fertile control couples and couples experiencing recurrent pregnancy loss. Similar results were also obtained when comparing women or men respectively from each group. CONCLUSION: IL-1RN 2 allele is not a risk factor for recurrent pregnancy loss.     

PKC stimulated by glucagon decreases UT-A1 urea transporter expression in rat IMCD

It is well-known that glucagon increases fractional excretion of urea in rats after a protein intravenous infusion. This effect was investigated by using: (a) in vitro microperfusion technique to measure [¹⁴C]-urea permeability (Pu × 10⁻⁵cm/s) in inner medullary collecting ducts (IMCD) from normal rats in the presence of 10⁻⁷M of glucagon and in the absence of vasopressin and (b) immunoblot techniques to determine urea transporter expression in tubule suspension incubated with the same glucagon concentration. Seven groups of IMCDs (n = 47) were studied. Our results revealed that: (a) glucagon decreased urea reabsorption dose-dependently; (b) the glucagon antagonist des-His¹-[Glu⁹], blocked the glucagon action but not vasopressin action; (c) the phorbol myristate acetate, decreased urea reabsorption but (d) staurosporin, restored its effect; e) staurosporin decreased glucagon action, and finally, (f) glucagon decreased UT-A1 expression. We can conclude that glucagon reduces UT-A1 expression via a glucagon receptor by stimulating PKC.     

Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients

The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2 mg, and tropisetron 5 mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.     

Signaling of endothelial cytoprotection in transplantation

A better knowledge of the processes by which endothelium can resist to cell death and adapt to injury by specific intracellular signaling pathways and dedicated protein regulation is a key step to understand how vascular inflammation/injury develops and how it is regulated. This review focuses on signaling pathways and molecular effectors that trigger the balance between endothelial cell activation and dysfunction. In addition to the canonical nuclear factor-κB (NF-κB), phosphatidyl inositol 3-kinase (PI-3K) and mitogen-activated protein kinases (MAPK) that orchestrated the inflammatory response and its termination we report here additive pathways such as Notch pathway and protein C/protease activated receptor (PAR) pathway that have been also reported to play a role in the control of EC activation and apoptosis. This review also provides an update of the characteristics of some established and novel protective molecules for the endothelium, identified in transplantation.     

Cocaine-taking and cocaine-seeking behaviors in rats remain stable after systemic administration of GYKI 52466: a non-competitive AMPA receptor antagonist

Given the posited role of enhanced AMPA-mediated synaptic transmission in relapse to drug seeking, we investigated whether systemic administration of the AMPA receptor antagonist GYKI 52466 inhibits cocaine-taking and cocaine-seeking behavior in rats. Rats were trained to self-administer cocaine until stable self-administration was achieved. Effects of GYKI 52466 (1, 3, or 10 mg/kg, i.v.) on cocaine self-administration were assessed. Animals were allowed to re-establish stable cocaine self-administration and were then behaviorally extinguished from drug taking. The effects of GYKI 52466 (3, 10 mg/kg, i.v.) on cocaine-induced reinstatement of drug-seeking behavior were assessed. We found that GYKI 52466 failed to inhibit cocaine-taking and cocaine-seeking in both the self-administration and reinstatement paradigms. We suggest that although AMPA receptors may be involved in cocaine reward and addiction, the AMPA receptor antagonist GYKI 52466 has low therapeutic potential for cocaine addiction treatment.