Ursolic acid promotes the release of macrophage migration inhibitory factor via ERK2 activation in resting mouse macrophages

Macrophage migration inhibitory factor (MIF) plays some pivotal roles in innate immunity and inflammation. Ursolic acid (UA), an anti-inflammatory triterpene carboxylic acid, was recently reported to induce the release of pro-inflammatory mediators in resting macrophages (Mvarphi). We investigated the effects of UA on MIF protein release in resting RAW264.7 mouse Mvarphi, and found that it decreased intracellular MIF protein levels and promoted the release of MIF into the culture media in dose- and time-dependent manners, without affecting mRNA levels. Further, the triterpene strikingly induced activation of mitogen-activated protein kinase kinase 1/2 (MEK1/2) and extracellular signal-regulated kinase 1/2 (ERK1/2) within 30min, whereas no phosphorylation of p38 MAPK or JNK protein was observed. In addition, UA-promoted MIF release was significantly inhibited by PD98059, a MEK1/2 inhibitor, while siRNA for ERK2, but not ERK1, significantly decreased the amount of MIF protein released. These results suggest that UA triggers the release of intracellular MIF protein through the ERK2 activation.     

1,10-Phenanthroline stabilizes mRNA of the carcinogen-metabolizing enzyme,cytochrome P450 1a1

1,10-phenanthroline (phen), flufenamic acid, and indomethacin are inhibitors of aldo-keto reductases 1C1 (AKR1C1), but only phen decreased the benzo[a]pyrene (BaP)-induced cytochrome P450 1a1 (Cyp1a1) protein level. Therefore the decrease in the BaP-induced Cyp1a1 protein level was not due to inhibition of Akr1c1, but to phen itself. Phen decreased the BaP-induced Cyp1a1 promoter activity and protein expression, and in contrast, it increased Cyp1a1 mRNA, resulting from an increase in mRNA stability. Phen is also known as a transition metal ion-chelator. Along with the phen study, we also found that Zn²⁺, Fe²⁺ and Cu²⁺ increased Cyp1a1 mRNA and protein stability. Our results show that phen stabilized the mRNA of Cyp1a1, although it decreased cell viability. In addition, Zn²⁺ and Fe²⁺ highly neutralized phen's suppression of Cyp1a1 protein expression, but they only slightly neutralized phen's promotion of mRNA stability and suppression of cell viability, and had no effect on phen's suppression of promoter activity. Phen's effect on Cyp1a1 expression was reversible, which indicates that phen is non-covalently linked to its target. This report elucidates a new role for phen of stabilizing Cyp1a1 mRNA, and provides information for further studies on mRNA stabilization.     

Twenty-eight days repeated oral dose toxicity study of gemifloxacin in Wistar albino rats

The purpose of this study was to investigate the potential toxicity of gemifloxacin by 28-day repeated oral dose in Wistar albino rats. The test article, was administered daily by gavage to male and female rats at dose levels of 0, 50, 100, 200 mg/kg/day. At the end of treatment period, 12 rats/sex/group was sacrificed, while six extra rats/sex in the vehicle control and highest dose groups sacrificed after 14 days recovery period. During the treatment and recovery periods, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, phototoxicity, hematology, serum biochemistry, synovial fluid biochemistry, electrocardiogram (ECG), gross findings, organ weights, microscopic examination of synovial fluid, and histopathology were examined. Hematological and serum biochemical investigations revealed a dose-dependent increase in the total white blood cell (WBC), total bilirubin (T-BIL), glucose (GLU), alanine aminotransferase (ALT) and significant decreases in total protein (TP) were observed in both sexes at the same dose, at the end of treatment period, but the levels returned toward normal during the recovery period. Histopathology of talar joint showed that erosion of the articular surface of that joint in both sexes at the end of treatment period at the dose level of 200 mg/kg/day. Degenerative changes in tendinocytes were observed in Achilles tendon of both sexes at the high dose level at the end of treatment period. In histopathological study shows partial effacement of liver architecture and focal ulceration in gastric mucosa at the high dose level at the end of treatment period. Based on these results, it was concluded that 28 days repeated oral dose of gemifloxacin caused increases in the liver weight, WBC count, T-BIL, glucose level, ALT, decreasing the TP, cause chronic hepatitis and acute gastritis, erosion of the articular surface of joint and histopathologic changes in Achilles tendon in rats at the dose level of 200 mg/kg/day.     

冠心病多种高危因素检测结果

目的探讨超敏C反应蛋白（HS-CRP）、血脂（TC、TG、HDL-C、LDL-C）、血尿酸（BUA）、血糖（GLU）、D-二聚体（D-D）水平与冠心病（CHD）的关系。方法对在武汉大学人民医院住院的68例冠心病患者采用荧光免疫干式定量法测定HS-CRP,采用酶比色法测定TC、TG、HDL-C、LDL-C和BUA,采用免疫比浊法测定D-D水平。用SPSS 11.0统计软件对试验数据进行统计分析。结果冠心病患者HS-CRP、TG、GIU、RUA和D-D水平均明显比健康对照组高（P〈0.01）,HDL-C却比对照组低（P〈0.01）;LDL-C、TC差异无统计学意义（P〉0.05）。结论炎症、高血脂、高血糖和高尿酸血症与冠心病的发生关系密切。     

彩色多普勒对脐绕颈胎儿脐动脉及大脑中动脉血流检测分析

目的　分析脐绕颈胎儿脐动脉（ＵＡ） 及大脑中动脉（ ＭＣＡ） 的血流参数,为临床判断胎儿脑供血情况提供客观依据。方法　比较４４ 例脐绕颈剖腹产胎儿与６１ 例脐绕颈自然分娩胎儿的脐动脉及大脑中动脉血流多普勒参数,以ＲＩ及ＶＰ为分析指标。结果　该两组脐绕颈胎儿ＵＡ 的ＲＩ及ＶＰ 有显著性差异,ＭＣＡ 的ＲＩ有显著性差异,剖腹产胎儿ＭＣＡ 的血流特点为阻力增高（ＲＩ０ ．６７ ±０ ．０２） 。结论　脐绕颈胎儿ＭＣＡ 的血流阻力增高（ＲＩ＞ ０ ．６５）应作为剖腹产术的临床参考指标。     

冠心宁注射液联合血栓通注射液治疗不稳定型心绞痛临床研究

目的:观察冠心宁注射液联合血栓通注射液治疗冠心病不稳定型心绞痛(UA)的临床疗效。方法:在常规治疗的基础上,治疗组50例另用冠心宁注射液联合血栓通注射液,对照组50例另用葛根素注射液,疗程均为2周。结果:总有效率治疗组88.0%、对照组78.0%,两组比较有显著性差异(P0.05)。治疗后两组心绞痛发作次数、心绞痛持续时间、CRP、血液流变学指标以及硝酸甘油用量均有改善,与治疗前比较有显著性差异(P0.05),但治疗组改善更明显(P0.05)。结论:冠心宁注射液联合血栓通注射液治疗冠心病UA有较好疗效,其作用机制可能与降低血清CRP、改善血液流变学水平以防止不稳定斑块破裂有关。     

生化分析仪的两个模块检测大鼠血清生化结果的比较

目的探讨生化分析仪的两个模块检测大鼠血清的差异。方法在同一实验室相同的运行环境下,使用日立7600生化分析仪的D和P两个不同模块,同时检测大鼠血清尿酸(UA)、总胆固醇(TC)、甘油三酯(TG)和高密度脂蛋白胆固醇(HDL-C)。结果日立7600生化分析仪D和P两个模块检测大鼠血清结果差异无统计学意义(尿酸t=1.751,总胆固醇t=-1.318,甘油三酯t=-1.472,高密度脂蛋白胆固醇t=1.941,P0.05),两个模块测定大鼠血清UA、TC、TG和HDL-C相关系数r分别是0.993、0.992、0.999、0.996。结论日立7600生化分析仪的两个不同模块检测大鼠血清UA、TC、TG和HDL-C结果有良好的一致性。     

解毒通脉胶囊治疗UA热毒痰瘀型临床疗效研究简

目的：探讨解毒通脉胶囊对UA热毒痰瘀型的临床疗效。方法：参照卫生部2002年颁布的《中药新药治疗冠心病心绞痛}性床研究指导原则》,将90例UA热毒痰瘀型患者按2：1随机分为治疗组和对照组,治疗组用解毒通脉胶囊,对照组用通心络胶囊,用药4周后比较两组疗效。结果：治疗组疗效优于对照组,两组疗效比较差异有统计学意义（P〈0．05）。结论：解毒通脉胶囊治疗UA热毒痰瘀型效果显著,值得临床广泛推广。     

南京地区高尿酸血症患者性别与年龄特征分析

目的 探索南京地区高尿酸血症(HUA)患者的性别与年龄特征。方法 以13 924名体检人员为研究对象,其中男性7 280人,女性6 644人,采用酶比色法检测尿酸(UA)。统计UA频数分布,比较不同年龄组男女HUA检出率。结果 男性、女性UA值分布均符合正态分布;在≤ 29、30～39、40～49、50～59岁年龄组中,男性HUA检出率明显高于女性(P＜0.01);在70～79、 ≥80岁年龄组中,女性HUA检出率明显高于男性(P＜0.05)。男性各相邻年龄组HUA检出率变化不明显,仅≥80岁组显著高于70～79岁组(P＜0.05)。女性从≤ 29岁组至30～39岁组,HUA检出率明显下降(P＜0.05);40～49岁组至60～69岁组以及70～79岁组至 ≥80岁组,HUA检出率均明显升高(P＜0.05)。结论 男性总体HUA检出率高于女性;男性在80岁之前HUA检出率随年龄增加而降低,女性50岁之后HUA检出率随年龄增加而升高。