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.     

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。     

慢性乙型病毒性肝炎治疗新方法

就当前慢性乙肝治疗的新方法、新进展作一综述。     

T细胞共刺激信号诱导器官移植免疫耐受的研究进展

人们通过阻断T细胞共刺激信号在小动物实验成功导出抗原特异性的免疫耐受，共刺激信号是T细胞充分活化必需的信号，主要是由CD28和TNF：TNFR两大家族的成员介导的。若阻断此共刺激信号，T细胞不能有效活化和增殖，从而达到免疫耐受状态。     

外伤性脾切除术后中医证候及免疫功能的研究

目的:研究外伤性脾切除术后中医辨证与免疫功能变化的关系.方法:选择15例脾切除和15例非脾切除患者作为观察对象,以其症状、舌苔、脉象及免疫功能的测定作为观察指标,观察其中医辨证与免疫功能变化.结果:脾切除组在术后早期可出现脾胃虚弱的证候群,同时免疫功能测定补体C3、免疫球蛋白IgG、免疫球蛋白IgM的水平明显降低,与非脾切除组有显著性差异.结论:脾切除容易造成患者术后出现的脾胃虚弱症候群,并降低患者的免疫功能.     

派立明与贝特舒联合应用对降眼压的临床观察

目的评价1.00%派立明(AZOPT)与0.25%贝特舒点眼液每日两次点眼对原发性开角型青光眼、高眼压症及抗青光眼术后高眼压的降眼压效果及安全性。方法31例患者51只眼纳入为期2个月的前瞻性研究。在停用其他抗青光眼药物足够长的时间后测量基础值,用药后每2周复查一次共4次,同时观察眼局部及全身副作用。结果用药前眼压为23.85±1.80 mmHg,4次随访眼压下降均值6.55 mmHg(6.06～7.04),眼压下降率27.50%(26.62～28.59%)。少数病例出现烧灼感、视物模糊、口苦等症状,均为轻度能耐受,对视力、眼底无影响。结论派立明与贝特舒联合用药具有稳定的降眼压效果,具良好耐受性。     

Synthesis of [3H] vardenafil,Levitra®, using a new labeling technique

Tritium was introduced into the new orally active, selective phosphodiesterase type V (PDE V) inhibitor vardenafil (Levitra^®), by reduction of a suitable amide precursor with freshly prepared lithium aluminum tritide. A specific activity of 52.7 Ci/mmol (1.95 TBq/mmol) was achieved. In order to overcome the usual technical difficulties during the preparation of complex tritides a new and easy labeling technique which has considerable potential for various tritia‐tion procedures, was developed. Copyright © 2003 John Wiley & Sons, Ltd.     

Changes in the ratio of urinary α1-microglobulin to ulinastatin levels in patients with Alzheimer-type dementia and vascular dementia

Abstract Relationships between urinary levels of α1-microglobulin (α1M) and ulinastatin (UT) in patients with dementia were investigated. There were no significant differences in α1M and UT levels and α1M: UT ratios among three groups: age-matched control subjects, patients with either Alzheimer-type senile dementia (ATD) or vascular dementia (VD). Although a positive correlation was established between α1M and UT levels in these groups, the regression of the demented patients differed significantly from that of controls ( P <0.05). A tendency towards a negative correlation between α1M: UT ratios and the levels of severity or duration of the disease was displayed in the ATD group, whereas a tendency toward a positive correlation between α1M: UT ratios and the levels of severity was observed in the VD group. These results suggest that changes in the relationships between urinary levels of α1M and UT may provide a useful biochemical index for diagnoses of ATD and VD.     

夹竹桃甙对Na~+、K~+-ATP酶抑制的动力学研究

本文对夹竹桃甙抑制Na~+、K~+-ATP酶的动力学作了探讨,并与乌本甙的作用进行了比较。结果表明:夹竹桃甙抑制Na~+、K~+-ATP酶,在Na~+、K~+浓度改变对均为非竞争性抑制,Na~+/K~+比例6:1时,为混合性抑制,而ATP对夹竹桃甙的作用几无影响。     

石杉碱甲类似物的研究II.N-甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲(1)是从中草药石杉属植物千层塔(Lycopodium serratum Thunb.)中分得的一种高效可逆的乙酰胆碱酯酶抑制剂,临床试验证实它对早老性痴呆症有显著疗效。本文报道N-甲基吡啶酮石杉碱甲类似物2和3的合成。2-甲氧基-5-甲氧羰基-11-亚甲基-5,9-甲撑环辛-7-烯并吡啶(9)在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮10,再用甲醇钠和碘甲烷甲基化得N-甲基吡啶酮11,11经碱性水解,Curtius重排和氨基的脱保护得N-甲基吡啶酮石杉碱甲类似物2。通过类似的途径从中间体2-甲氧基-5-甲氧羰基-7-甲基-11-酮-5,9-甲撑环辛-7-烯并吡啶(14)合成了类似物3。类似物2和3的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。