L‐type Ca2+ channel opener BayK 8644‐induced Ca2+ influx and Ca2+ release in human oral cancer cells (OC2)

The effect of BayK 8644, a chemical widely used to activate L‐type Ca²⁺ channels, on cytosolic free Ca²⁺ concentrations ([Ca²⁺]_i) in human oral cancer cells (OC2) has not been explored to date. The present study examined whether BayK 8644 altered basal [Ca²⁺]_i levels in suspended OC2 cells by using fura‐2. BayK 8644 (10 pM–10 µM) increased [Ca²⁺]_i in a concentration‐dependent manner. The Ca²⁺ signal was reduced partly by removing extracellular Ca²⁺. BayK 8644‐induced Ca²⁺ influx was blocked by nifedipine, but was not altered by the store‐operated Ca²⁺ entry inhibitors, econazole and SKF96365; protein kinase C modulators phorbol 12‐myristate 13‐acetate (PMA) and GF109203X; the protein kinase A inhibitor H89; and the phospholipase A₂ inhibitor, aristolochic acid. In Ca²⁺‐free medium, after pretreatment with 1 µM BayK 8644, 1 µM thapsigargin (an endoplasmic reticulum Ca²⁺ pump inhibitor)‐induced [Ca²⁺]_i rises were abolished; and conversely, thapsigargin pretreatment abolished BayK 8644‐induced [Ca²⁺]_i rises. Inhibition of phospholipase C with U73122 did not change BayK 8644‐induced [Ca²⁺]_i rises. Collectively, in OC2 cells, BayK 8644 induced [Ca²⁺]_i rises by causing phospholipase C‐independent Ca²⁺ release from the endoplasmic reticulum; and Ca²⁺ influx via L‐type Ca²⁺ channels. Drug Dev Res 69: 2008. © 2008 Wiley‐Liss, Inc.     

缓控释给药系统在中药口服缓控释制剂中的应用研究与思考

介绍中药口服缓控释制剂的研究应用。对研究过程中存在的难点问题作了分析。     

复方加替沙星滴耳液的制备及质量控制

目的探讨复方加替沙星滴耳液的制备及建立其质量控制。方法以加替沙星和甲硝唑为主药，以甘油和乙醇为溶剂制备滴耳液，采用双波长分光光度法测定两主药含量，并进行稳定性考察。结果加替沙星和甲硝唑的平均回收率分别为．98．43％（RSD=0．68％）和98．92％（RSD=0．73％），制剂有效期达2年以上。结论本制荆制备工艺简单、稳定性好，质量控制方法简易、快速、可行。     

Motorcycle exhaust induces reproductive toxicity and testicular interleukin-6 in male rats.

Motorcycle exhaust (ME) from two-stroke engines contains many toxicants and poses a potential health hazard. The major objectives of the present study were to investigate the male reproductive toxicity of ME and the underlying mechanisms of toxicity. Male Wistar rats were exposed to ME by inhalation 1 h each in the morning and afternoon, Monday through Friday. Exposures to 1:50 diluted ME for 4 weeks or to 1:10 diluted ME for 2 and 4 weeks showed concentration- and time-dependent decreases of testicular weight, spermatid number, and cauda epididymal sperm number. Subsequent studies were done using 4-week exposure to 1:10 diluted ME. ME caused histopathological changes including testicular spermatocytic necrosis and seminiferous tubule atrophy and cauda epididymal formation of clusters of pyknotic and necrotic sperm cells. ME-exposed male rats mated with untreated females showed decreases of male mating index and female fertility index and an increase of implantation site loss. ME decreased 7-ethoxycoumarin O-deethylase and superoxide dismutase activities but induced proinflammatory cytokine interleukin-6 (IL-6) messenger RNA (mRNA) in the testis. Male rats were exposed to ME with or without cotreatment with 50 mg/kg vitamin E orally for 4 weeks. ME decreased serum testosterone concentration. This effect was reversed by cotreatment with vitamin E. ME decreased testicular spermatid number and induced IL-6 mRNA and protein. These effects were also reversed by the vitamin E cotreatment. The present findings show that ME causes male reproductive effects and induces testicular IL-6 in rats by mechanisms involving induction of oxidative stress and inhibition of steroidogenesis.     

Selection of agents for prevention of cisplatin-induced hepatotoxicity.

The objective of this study was to explore the optimal combination of agents used along with cisplatin for protection of hepatotoxicity. Animal experiment was carried out based on the orthogonal design L(8) (2(7)) setting seven factors with two different levels of each, and eight groups of mice were needed. The agents tested in this study were zinc, selenium, fosfomycin, sodium thiosulfate (STS), N-acetyl-cysteine (NAC), methionine and taurine. Mice were supplemented by gavage with various combinations of agents as designed in the orthogonal table once a day for nine days beginning two days before cisplatin administration. 3.5mg/kg body weight of cisplatin was given intraperitoneally once a day for five days simultaneously. After cessation of cisplatin administration, the agents were supplemented continuously for two days. Activities of alanine aminotransferase (ALT) in serum, levels of glutathione (GSH) and malondialdehyde (MDA) in liver were analyzed after cessation of supplementation. Results showed zinc, fosfomycin and methionine were the effective factors for protection of weight loss; fosfomycin and methionine were the effective factors for prevention of decreased liver ratio; selenium, fosfomycin and STS were the effective factors for prevention of increased ALT activities in serum. On the other hand, methionine was the only effective factor for prevention of decreased GSH levels in liver; zinc, selenium and fosfomycin were the effective factors for prevention of increased MDA levels in liver. Based on the data observed in this study, the optimum combinations of agents were selenium, fosfomycin, methionine and taurine, and zinc, selenium, STS and methionine. In conclusion, each agent used in this study could play a beneficial role for prevention of cisplatin hepatotoxicity, however, none could play the crucial role. The potentiated actions for prevention of cisplatin hepatotoxicity could be achieved via combined use of these agents.     

抗TGF—β2抗体对滤过泡瘢痕成纤维细胞Ⅰ、Ⅲ型胶原蛋白表达的影响

目的 观察抗转化生长因子-β2(TGF-β2)抗体对体外培养的滤过泡成纤维细胞Ⅰ、Ⅲ型胶原蛋白表达的影响.方法 利用手术修复人眼小梁切除术后失败滤过泡修复时切除下来的瘢痕组织进行组织块培养,获得成纤维细胞(FB).将0、0.01、0.1、1μg/mL抗TGF-β2抗体作用于FB 24h以及0.14μg/mL(半数抑制率质量浓度,IC50)抗体作用0、24、48、72h,通过生物化学显色法、RT-PCR法检测抗TGF-β2抗体对成纤维细胞Ⅰ、Ⅲ型胶原蛋白的表达量. 结果在FB中加入0、0.01、0.1、1μg/mL抗TGF-β2抗体作用24h及IC50质量浓度处理0、24、48、72h,结果显示随着抗TGF-β2抗体质量浓度增加及作用时间延长,Ⅰ、Ⅲ型胶原mRNA表达依次减少,羟脯氨酸(HPr)及胶原含量逐渐降低(P＜0.05).结论 抗TGF-β2抗体能减少Ⅰ、Ⅲ型胶原蛋白的表达及合成.     

改良直肌移位联合内直肌后徙术治疗麻痹性内斜视

目的 探讨一种改良Hummelsheim术式治疗完全性外展神经麻痹所致内斜视的临床疗效.方法 对Hummelsheim及Jensen术式进行综合并加以改良后,为13例各种原因导致的外展神经麻痹患者施行该术式并同时行相应内直肌后徙术治疗.观察术后原在位眼位、代偿头位及复视的改善情况.随访期9～36月,平均11.4个月.结果 13例中,术后原在位眼位<+10△,11例代偿头位消失,达84.6%,术后1次矫正满意率为84.6%.随访期内未发现眼位回退现象.结论 改良的Hummelsheim术式是一种有效的治疗麻痹性内斜视的手术方法.     

呼吸道合胞病毒对Hep-2细胞增殖的影响

目的研究呼吸道合胞病毒(RSV)感染对细胞增殖活性的影响。方法培养RSV感染Hep-2细胞,观察细胞形态,在感染后不同时间点用四甲基偶氮唑盐(MTT)法检测Hep-2细胞增殖情况。结果RSV感染Hep-2细胞后48 h细胞开始出现病变,72~96 h病变最明显,120 h细胞全部死亡,不存在正常细胞。感染后24 h4、8 h、72 h9、6 h1、20 h Hep-2细胞的增殖指数分别为0.85,1.2,1.08,0.90,0.74。结论呼吸道合胞病毒感染早期促进宿主Hep-2细胞增殖,晚期抑制增殖。     

FQ-PCR方法检测女性CA患者HPV_(6、11)和HPV_(16、18)的实验研究

目的:探讨女性尖锐湿疣(CA)患者HPV6、11型和HPV16、18型的感染情况。方法:采用荧光定量聚合酶链反应(FQ-PCR)方法检测216例女性CA患者疣体组织或分泌物中的HPV6、11型和HPV16、18型。结果:HPV6、11型阳性率为94.91%(205/216),HPV16、18型阳性率为16.20%(35/216),HPV6、11型和HPV16、18型同时阳性的感染率为12.50%(27/216)。定量测定结果显示,HPV6、11型患者病毒载量最高1.0×108 copies/ml,最低2.8×103copies/ml;HPV16、18型患者病毒载量最高1.0×108 copies/ml,最低2.57×104 copies/ml。结论:FQ-PCR技术具有灵敏、简捷、安全、特异性强的特点,避免了单纯PCR扩增产生的假阳性。女性尖锐湿疣患者应用此方法检测HPV阳性率高,可以快速区分高危型及低危型的HPV感染,有助于对尖锐湿疣的复发和癌变作出可能性预测。