介导感觉生理功能的瞬时受体电位通道蛋白(TRP)家族研究进展

瞬时受体电位通道蛋白(TRP)家族由一类特殊的阳离子通道蛋白组成,在神经细胞及其他非兴奋细胞中有重要作用,其中在介导多种感觉生理功能方面的作用尤其显著.TRP结构与功能的深入研究为阐明感觉生理功能的分子机制提供了重要线索.本文综述TRP家族在温度感受、机械刺激感受、光感受和化学信号感受等方面的研究进展.     

An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.

Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.     

Influence of bradykinin B1 and B2 receptors in the immune response triggered by renal ischemia–reperfusion injury

Bradykinin B1 receptors are exclusively expressed in inflamed tissues. For this reason, they have been related with the outcomes of several pathologies. Ischemia–reperfusion injury is caused by the activation of inflammatory and cytoprotective genes, such as macrophage chemoattractant protein-1 and heme oxygenase-1, respectively. This study was aimed to analyze the involvement of bradykinin B1 and B2 receptors (B1R and B2R) in tissue response after renal ischemia–reperfusion injury. For that, B1R (B1−/−), B2R (B2−/−) knockout animals and its control (wild-type mice, B1B2+/+) were subjected to renal bilateral ischemia, followed by 24, 48 and 120 h of reperfusion. At these time points, blood serum samples were collected for creatinine and urea dosages. Kidneys were harvested for histology and molecular analyses by real-time PCR. At 24 and 48 h of reperfusion, B1−/− group resulted in the lowest serum creatinine and urea levels, indicating less renal damage, which was proved by renal histology. Renal protection associated with B1−/− mice was also related with higher expression of HO-1 and lower expression of MCP-1. In conclusion, the absence of B1R had a protective role against inflammatory responses developed after renal ischemia–reperfusion injury.     

肿瘤微环境对树突细胞功能状态的影响

目的：探讨肿瘤细胞分泌的可溶性细胞因子营造的微环境对树突细胞(DCs，dendritic cells)的分化发育的影响，以进一步揭示肿瘤的免疫逃逸机制。方法：用免疫磁珠从人外周血分离CD14^ 单核细胞，加入粒细胞巨噬细胞集落刺激因子(GM-CSF)、白细胞介素4(IL-4)和人白血病细胞Jurkat培养上清液体外培养DCs，以正常培养诱导的DCs作为对照，采用傅立叶变换红外光谱(FTIR)技术分析人白血病细胞培养上清液对DCs分化发育的影响。结果：正常培养DCs与肿瘤上清液培养的DCs相比，在细胞内蛋白质和核酸的相对含量和细胞内消耗葡萄糖重新合成磷脂的量方面差异无显著性，但是，在细胞的转录状态方面差异有显著性。结论：肿瘤细胞上清液培养液所营造的微环境细胞转录水平上对DCs的功能状态有明显的抑制作用。     

14-3-3蛋白与细胞凋亡

14 3 3蛋白是Moore和Pere于 196 7年发现的 ,当时他们认为 14 3 3蛋白是脑所特有的一种酸性蛋白 ,并依据其在DEAE 纤维素色谱上的组分数以及在淀粉凝胶电泳中的迁移位置而命名为 14 3 3蛋白。但随后的大量研究表明14 3 3蛋白在所有的真核细胞中均有表达 ,是一个调节蛋白家族 ,能与许多功能不同的信号蛋白结合 ,例如蛋白激酶Raf 1、KSR 1、Bcr、Ca2 +/钙调蛋白激酶、PKC、蛋白磷酸酶cdc2 5c、促凋亡蛋白BAD、抗凋亡蛋白A2 0 、跨膜蛋白受体GA等。这就说明 14 3 3蛋白在信号传导、细胞周期调控、细胞凋亡等过程中具有极其重要的…     

Risk factors of type 2 diabetes among Korean adults: The 2001 Korean national health and nutrition examination survey

This study aimed to identify risk factors for type 2 diabetes (T2D) in Korea, a rapidly changing country. Data of 5,132 adults aged 20-85 were used from the 2001 Korean Health and Nutrition Examination Survey. Multiple logistic regression was carried out to identify risk factors for T2D. Three models were specified: (i) socioeconomic and demographic factors (model 1: age, gender, education, poverty income ratio, employment), (ii) behavioral risk factors and covariates (model 2: obesity, physical activity, smoking, alcohol drinking, dietary quality, family history of T2D, co-morbidity) and (iii) socioeconomic, demographic, and behavioral factors (model 3). The prevalence of T2D was 7.4%. Less education (OR 1.41, 95% CI 1.08-1.84), age (OR 2.19, 95% CI 1.56-3.08 in 40-59 yrs, OR 4.05, 95% CI 2.76-5.95 in 60 yrs + comparing to 20-39 yrs) and abdominal obesity (OR 2.24, 95% CI 1.79-2.82) were risk factors for T2D even after controlling for other factors simultaneously. There was a significant association of T2D with ever smoking (OR 1.34, 95% CI 1.06-1.67). The relationship of age with T2D was modified by gender in model 1 and the relationship of smoking with T2D was modified by obesity in model 2. Less educated, older, obese or ever smokers were more likely to have T2D. Gender mediated the relationship of age, and obesity mediated the relationship of smoking, with T2D. Intervention programs for T2D in Korea should take the interactions among risk factors into account.     

乳腺癌患者外周血EMA和EGP-2mRNA的表达及其临床意义

目的 探讨上皮膜抗原(EMA)和表皮糖蛋白基因(EGP-2)在乳腺癌患者外周血中的表达及其与肿瘤微转移的关系. 方法采用RT-PCR方法检测53例乳腺癌患者(乳癌组)和24例乳腺良性疾病患者(良性病组)EMA和EGP-2mRNA在外周血中的表达,并分析其与临床指标之间的关系. 结果乳癌组外周血EMA和EGP-2mRNA的表达率分别为33.96%和28.30%,而在良性病组外周血表达率分别为0和4.17%,差异均有统计学意义(P＜0.05).EMA和EGP-2mRNA的检出率与腋窝淋巴结转移、TNM分期等临床参数呈正相关;EMA和EGP-2mRNA联合检测敏感度和准确性在乳腺癌组分别为52.83%和66.23%,相对于EPG-2 mRNA单项检测敏感度及准确性有明显升高,但与EMA mRNA无统计学差异.结论 EMA和EGP-2联合检测时准确性明显升高,故两者可作为标志物检测乳腺癌患者外周血微转移,有可能对乳腺癌的疗效和预后判断有意义.     

Cyclooxygenase-2 inhibition increases gastric tone and delays gastric emptying in rats.

We evaluated the effects of cyclooxygenase-2 (COX-2) selective inhibitors, COX-1 selective inhibitor, or COX non-selective inhibitor on gastric emptying and intestinal transit of liquids, and evaluated the effect of a COX-2 selective inhibitor on gastric tonus (GT). Male Wistar rats were treated per os with saline (control), rofecoxib, celecoxib, ketorolac, rofecoxib + ketorolac, celecoxib + ketorolac, or indomethacin. After 1 h, rats were gavage-fed (1.5 mL) with the test meal (5% glucose solution with 0.05 g mL(-1) phenol red) and killed 10, 20 or 30 min later. Gastric, proximal, medial or distal small intestine dye recovery (GDR and IDR, respectively) were measured by spectrophotometry. The animals of the other group were treated with i.v. valdecoxib or saline, and GT was continuously observed for 120 min using a pletismomether system. Compared with the control group, treatment with COX-2 inhibitors, alone or with ketocolac, as well as with indomethacin increased GDR (P < 0.05) at 10-, 20- or 30-min postprandial intervals. Ketorolac alone did not change the GDR, but increased the proximal IDR (P < 0.05) at 10 min, and decreased medial IDR (P < 0.05) at 10 and 20 min. Valdecoxib increased (P < 0.01) GT 60, 80 and 100 min after administration. In conclusion, COX-2 inhibition delayed the gastric emptying of liquids and increased GT in rats.     

2005～2007年我国非甾体抗炎药市场应用分析

目的：以骨骼肌肉系统使用非甾体抗炎药物为例，分析该类药物在2005～2007年的销售数量、销售金额及生产厂家风云榜。方法：采用药物分类累加的方法统计2005～2007年非甾体抗炎药的销售数量和金额排序，并对前10位药品销售数量和金额对比，及前10位厂家对比。结果：双氯芬酸稳居销售榜首，美洛昔康、布洛芬等药物位居其后。结论：新一代的非甾体抗炎药已经占据主要市场，各类药物各有特色，但是仍需注意其消化系统及心血管系统的不良反应。