BEMF对OVX-OP大鼠骨细胞凋亡的影响

目的 观察BEMF对 OVX-OP大鼠骨细胞凋亡的影响,探讨其治疗 OVX-OP的作用机制.方法 6月龄雌性未孕Wistar大鼠40只,按体质量随机分为模型组(OVX)、假手术组(Sham)、仿生电磁场治疗组(EM)、雌激素治疗组(E).OVX、EM、E组行双侧卵巢切除术,Sham组行假手术.术后第9周开始治疗:E组行苯甲酸雌二醇肌肉注射,0.5mg/kg,1次/2周.EM组大鼠暴露于仿生脉冲电磁场治疗,1h·次-1·d-1,OVX、Sham组不予任何处理,作为对照组.治疗10周后应用原位凋亡法计数腰椎松质骨骨细胞的凋亡指数、透射电镜观察骨细胞凋亡情况、免疫组化法观察骨细胞Fas、bax、bcl-2表达情况.结果 与OVX组相比, EM组骨细胞凋亡指数显著下降,差异有统计学意义(P＜0.01),透射电镜观察显示EM组骨细胞活性增强,无明显凋亡征象,而OVX组骨细胞呈退行改变,可见异染色体凝聚、边集等典型细胞凋亡征象.EM组Fas阳性骨细胞数较OVX组显著性减少, bax阳性骨细胞数与bcl-2阳性骨细胞数比值显著减少,差异有统计学意义(P＜0.01).结论 BEMF对 OVX-OP骨细胞凋亡的抑制作用,可能是其治疗 OVX-OP的机制之一.     

一项左旋多巴乙酯对伴有运动波动帕金森病患者疗效的随机对照试验

背景：运动波动是长期接受左旋多巴治疗的帕金森病（PD）患者的一个常见并发症。胃排空减慢及胃肠道左旋多巴溶解性差会延迟给药后疗效的产生。左旋多巴乙酯作为左旋多巴的一种乙酯前体药物具有更好的胃溶性，可迅速进入小肠并快速水解成左旋多巴，缩短了左旋多巴达到最大浓度的时间。目的：确定左旋多巴乙酯对伴有运动波动PD患者的疗效、安全性和耐受性。设计：一项双盲、随机、比较的临床试验。机构：美国和加拿大的44个地区。患者：每日给予左旋多巴后至少需潜伏90min才能达到“开”期（TTON）的327例PD患者。干预：使用左旋多巴乙酯-卡比多巴或左旋多巴-卡比多巴治疗18周。主要观察指标：利用家庭日记测定每日总的TTON相对于基线的改变。结果：左旋多巴乙酯-卡比多巴治疗组平均每日总的TTON减少0．58h，而左旋多巴-卡比多巴治疗组减少了0．79h（P=0．24）。两治疗组在减少治疗无效方面无显著性差异（-6．82％vs-4．69％，P=0．20）。左旋多巴乙酯-卡比多巴（-0．85h）和左旋多巴-卡比多巴治疗组（-0．87h）每日总的“关”期都得到改善且未增加令人棘手的运动障碍。结论：从药物动力学理论上讲，左旋多巴乙酯尽管有优点，但与左旋多巴相比并未能改善TTON、治疗无效和“关”的时间。     

Neuroendocrine modulation of chronic relapsing experimental autoimmune encephalomyelitis: a critical role for the hypothalamic-pituitary-adrenal axis

Murine relapsing EAE can be profoundly suppressed by restraint stress (RST) administered beginning prior to neuroantigen immunization. This study determined what hormone pathway(s) mediate disease suppression. Our results showed that nadolol (NAD), a β₂-adrenergic antagonist, did not reverse the RST-induced suppression of EAE. However, administration of either RU486 or aminoglutethimide, which block the action of peripheral glucocorticoids, resulted in a partial reversal of EAE suppression. Administration of exogenous corticosterone mimicked the effects of RST, in terms of suppression of EAE, decrease in lymphoid cell numbers and decrease in Th1 cytokine production. Therefore, the HPA axis plays a more profound role in the RST-induced suppression of EAE than does the sympathetic nervous system.     

Effect of gonadotrophin-releasing hormone agonist treatment on growth hormone secretion in women with polycystic ovarian syndrome

The suppression of the pituitary-gonadal axis by the administration of gonadotrophin-releasing hormone agonists (GnRH-a) is used occasionally as an adjunct therapy with gonadotrophins for ovulation induction in women with polycystic ovarian syndrome (PCOS). A number of recent clinical studies have suggested that women with polycystic ovaries (PCO) may have disturbances of normal growth hormone (GH) kinetics and alterations in the GH/insulin-like growth factor (IGF)-I system. The purpose of this study was to determine the effect of GnRH-a administration on GH-releasing hormone (GHRH)-stimulated GH release in women with PCOS. Eight women with PCO and six control women were studied before and after 2 months of treatment with the long acting GnRH-a triptoreline (3.75 mg monthly injections). GHRH was given as a single i.v. injection and blood samples for GH measurements were obtained at -15, 0, 30, 60, 90 and 120 min. The GH responses were expressed as the area under the curve (AUC) or the differences from the basal value (delta(max)). The GH response to GHRH (mean +/- SEM) was lower in women with PCO (AUC 114.9 +/- 43.1 versus 206.2 +/- 28.7 ng/ml/120 min, P < 0.05 and delta(max) 31.6 +/- 8.2 versus 49.4 +/- 5.8 ng/ml, P < 0.05). After treatment with the GnRH-a, the GH response to GHRH was significantly smaller than before treatment in both groups (PCO AUC 34.6 +/- 9.0 ng/ml/120 min and delta(max) 12.4 +/- 3.1 ng/ml; controls AUC 148.8 +/- 28.4 ng/ml/120 min and delta(max) 31.2 +/- 6.1 ng/ml), but the PCO group had a significantly smaller response. These data demonstrate that women with PCO have a reduced GH response to GHRH compared with normal controls and that GnRH-a administration causes a further GH reduction in both groups. Women with PCO have a greater suppression of GH response to GHRH during treatment with GnRH-a. This suggests that a different level of sensitivity in the somatotrophic axis exists in PCOS.      

Identification of signaling motifs within human Fc gamma RIIa and Fc gamma RIIb isoforms

To assess the functional capacity of the heterogeneous Fc gamma RII (CD32) family and to identify critical regions for functioning, we generated a panel of B-cell transfectants. The Fc gamma R-negative B- cell line IIA1.6 was transfected with wild-type or mutant human Fc gamma RIIa and IIb molecules. Solely Fc gamma RIIa-expressing IIA1.6 cells were capable of phagocytosing opsonized Staphylococcus aureus bacteria, and cross-linking of Fc gamma RIIa triggered a rapid induction of tyrosine phosphorylation after 20 seconds. Analysis of Fc gamma RIIa mutants identified the immunoreceptor tyrosine-based activation motif (ITAM; previously described as ARH-1 motif) within the IIa cytoplasmic tail to be critical for B-cell activation. In contrast, Fc gamma RIIb isoforms triggered tyrosine phosphorylation on cross- linking with much slower kinetics (> 3 minutes) than Fc gamma RIIa. Furthermore, solely Fc gamma RIIb molecules proved capable of downregulating [Ca2+]i and interleukin-2 production on co-cross-linking with sIgG in IIA1.6. The Fc gamma RIIb-mediated functions were absent in Fc gamma RIIb mutants in which the tyrosine or leucine within the YSLL motif in a conserved 13-aa region (now known as immunoreceptor tyrosine-based inhibitor motif [ITIM]) were changed into phenylalanines. In conclusion, these data show the presence of functionally critical motifs within Fc gamma RII cytoplasmic tails. Fc gamma RIIa contains an ITAM involved in B-cell activatory functions, whereas the downregulatory activity of Fc gamma RIIb isoforms is linked to an ITIM.