二甲双胍和吡格列酮对2型糖尿病患者的疗效及抗氧化作用研究

目的 探讨二甲双胍或吡格列酮对2型糖尿病患者的疗效及其对超氧化物歧化酶（SOD）、丙二醛（MDA）的影响。方法 纳入北京市昌平区中西医结合医院收治的2型糖尿病患者160例,按随机数字表法平均分为二甲双胍组和吡格列酮组,分别给予盐酸二甲双胍肠溶片（1 g/次,每日2次）和盐酸吡格列酮片（30 mg/次,每日1次）,两组疗程均为4周。比较两组患者治疗前后空腹血糖（FPG）、餐后2 h血糖（PPPG）、糖化血红蛋白（HbA1c）,血脂以及两组患者SOD、MDA水平。结果 给予降糖药4周后,两组患者FPG、PPPG、HbA1c均显著下降,同组治疗前后比较差异有统计学意义（P<0.05）。治疗后,二甲双胍组患者三酰甘油（TG）、低密度脂蛋白（LDL）水平显著降低,同组治疗前后比较差异有统计学意义（P<0.05）,而吡格列酮患者则无显著性变化。吡格列酮组患者血清MDA水平下降,同组治疗前后比较差异有统计学意义（P<0.05）;二甲双胍组患者血清SOD水平显著上升（P<0.05）,且显著高于吡格列酮组（P<0.05）;吡格列酮组患者血清MDA水平显著下降（P<0.05）,且显著低于二甲双胍组（P<0.05）。结论 二甲双胍或吡格列酮均能改善胰岛素抵抗和糖尿病并发症;吡格列酮降低MDA水平效果优于二甲双胍,但增加SOD水平仅见于二甲双胍。两种药物对氧化应激的作用机制不同,有利于联合用药。     

金芪降糖片联合二甲双胍治疗2型糖尿病的临床研究

目的 探讨金芪降糖片联合二甲双胍治疗2型糖尿病的临床疗效和对血管内皮功能的影响。方法 选取2012年12月-2013年10月就诊于吉林油田总医院的2型糖尿病患者68例,随机分为治疗组（34例）和对照组（34例）。两组患者均进行糖尿病教育,均在糖尿病饮食、适当运动的基础上口服盐酸二甲双胍片,0.5 g/次,根据血糖水平调整每日剂量,最大剂量<2 g,3次/d;治疗组口服金芪降糖片,7片/次,3次/d,餐前0.5 h口服,其他同对照组。4周为1个疗程,两组患者均治疗2个疗程。观察两组患者的临床疗效,同时测定两组患者治疗前后糖代谢指标、血脂指标、血管内皮功能指标的变化。结果 治疗后,治疗组和对照组的总有效率分别为97.06%、91.18%,两组比较差异有统计学意义（P<0.05）。治疗后,两组患者的空腹血糖（FPG）、餐后2 h血糖（2h PG）、糖基化血红蛋白（HbAlc）均较治疗前明显降低,同组治疗前后差异有统计学意义（P<0.05、0.01）,治疗后,治疗组糖代谢指标较对照组改善更加明显,两组比较差异有统计学意义（P<0.05）。治疗后,两组患者的总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白（LDL-C）均较治疗前明显降低,同组治疗前后差异有统计学意义（P<0.05、0.01）;治疗后,治疗组血脂指标较对照组改善更加明显,两组比较差异有统计学意义（P<0.05）。治疗后,两组患者血清一氧化氮（NO）、内皮素（ET）、血栓素B₂（TXB₂）水平均较治疗前明显下降,6-酮-前列腺素1α（6-keto-PGF1α）与治疗前比较显著升高,同组治疗前后差异有统计学意义（P<0.05、0.01）;治疗后,治疗组指标较对照组改善更加明显,两组比较差异有统计学意义（P<0.01）。结论 金芪降糖片联合二甲双胍治疗2型糖尿病有较好的临床疗效,能较好的控制血糖水平,并可改善患者的血脂代谢和血管内皮功能,适合临床推广应用。     

元胡止痛片联合布洛芬和维生素B1治疗带状疱疹后遗神经痛的疗效观察

目的 观察元胡止痛片联合布洛芬缓释胶囊和维生素B₁片治疗带状疱疹后遗神经痛的临床疗效。方法 选取上海交通大学医学院附属第三人民医院2013年6月-2015年3月收治的带状疱疹后遗神经痛患者98例,随机分为对照组和治疗组,每组各49例。对照组给予布洛芬缓释胶囊0.3 g/次,2次/d,维生素B₁片10 mg/次,3次/d;治疗组在对照组的基础加用元胡止痛片5片/次,3次/d。两组均连续治疗4周。采用VAS法记录治疗前、治疗后24 h、1周、1个月时的VAS评分,对两组患者治疗前后的疼痛程度进行评估;记录两组患者止痛即刻起效时间、疼痛开始缓解时间;观察两组的临床疗效。结果 两组治疗后1周、1个月VAS评分均显著低于同组治疗前(P < 0.05)。治疗组在治疗后24 h、1周、1个月VAS评分均显著低于对照组对应的各时间点,其中治疗组治疗后1周、1个月VAS评分与对照组比较,差异均具有统计学意义(P < 0.05)。治疗后,治疗组止痛即刻起效时间短于对照组,但组间比较差异无显著性,两组疼痛开始缓解时间比较差异具有显著性(P < 0.05),治疗组优于对照组(P < 0.05)。治疗后,对照组和治疗组的总有效率分别为89.80%、97.96%,两组总有效率比较差异有统计学意义(P < 0.05)。结论 元胡止痛片联合布洛芬缓释胶囊和维生素B₁片治疗带状疱疹后遗神经痛具有较好的临床疗效,且安全可靠,具有一定的临床推广应用价值。     

脉络舒通丸治疗下肢血栓性浅静脉炎的临床研究

目的 观察脉络舒通丸治疗下肢血栓性浅静脉炎的临床疗效。方法 选取2018年1月—2020年12月安徽省第二人民医院收治的64例下肢血栓性浅静脉炎患者,根据治疗方案将患者分为对照组和观察组,每组32例。对照组采用基础治疗,观察组在对照组治疗方案基础上口服脉络舒通丸,12 g/次,3次/d。两组患者疗程均为2周。观察两组患者的临床疗效,同时比较两组治疗前后的临床症状评分、炎症因子及血液流变学指标水平。结果 治疗后,观察组总有效率为93.75%,显著高于对照组的84.38%,差异具有统计学意义（P<0.05）。治疗后,两组患者皮肤红肿、患肢肿胀、患肢疼痛以及筋脉条索评分均显著降低,差异具有统计学意义（P<0.05）;观察组患者临床体征情况优于对照组,差异具有统计学意义（P<0.05）。治疗后,两组患者白细胞介素-6（IL-6）和肿瘤坏死因子_-α（TNF_-α）水平均显著下降,差异具有统计学意义（P<0.05）。治疗后,观察组患者IL-6和TNF_-α水平显著低于对照组,差异具有统计学意义（P<0.05）。治疗后,两组患者血液流变学指标均显著改善,差异具有统计学意义（P<0.05）;观察组血液流变学指标显著优于对照组,差异具有统计学意义（P<0.05）。结论 在常规治疗下肢血栓性浅静脉炎的基础上加用脉络舒通丸能显著增加疗效,值得临床推广。     

注射用丹参多酚酸治疗发病48h～14d的缺血性脑卒中的疗效及对患者血Lp-PLA2及ox-LDL的影响

目的 探讨注射用丹参多酚酸对发病48 h～14 d的缺血性脑卒中患者的疗效及对患者血脂蛋白相关性磷脂酶A₂（Lp-PLA₂）及氧化修饰型低密度脂蛋白（ox-LDL）的影响。方法 选择2020年1月—2022年6月安阳市人民医院收治的发病48 h～14 d入院的260例缺血性脑卒中患者,按照治疗方案不同分为对照组和试验组,每组各130例,两组均给予缺血性脑卒中的常规治疗,对照组在常规治疗基础上给予注射用血塞通（冻干）,每次400 mg加入0.9%氯化钠注射液250 mL,静脉滴注,每天1次;试验组在对照组基础上给予注射用丹参多酚酸,每次取0.13 g加入0.9%氯化钠注射液250 mL,静脉滴注,每天1次。两组疗程均为14 d。比较两组临床疗效,分别于治疗前及治疗14 d后采用美国国立卫生研究院卒中量表（NIHSS）评分量表进行神经功能缺损评估,采用日常生活能力量表（ADL）评分进行日常生活能力评估,采用改良Rankin量表（mRS）评分评价神经功能恢复情况,治疗前及治疗14 d后测定两组患者血浆Lp-PLA₂及血清ox-LDL水平。观察治疗期间两组患者不良反应发生情况。结果 试验组总有效率为93.85%,显著高于对照组的87.69%（P＜0.05）。治疗前两组NIHSS、mRS、ADL评分比较,差异均无统计学意义（P＞0.05）;治疗14 d后两组NIHSS、mRS评分均较本组治疗前显著降低（P＜0.05）,且试验组显著低于对照组（P＜0.05）;治疗后,两组ADL评分均较本组治疗前显著升高（P＜0.05）;且试验组显著高于对照组（P＜0.05）。治疗前两组Lp-PLA₂及ox-LDL水平比较,差异均无统计学意义（P＞0.05）;在治疗14 d后两组Lp-PLA₂及ox-LDL水平均较本组治疗前显著降低（P＜0.05）,且试验组显著低于对照组（P＜0.05）。治疗期间,两组均未发生明显不良反应。结论 注射用丹参多酚酸能有效降低发病48 h～14 d的缺血性脑卒中患者血Lp-PLA₂及ox-LDL水平,能够改善临床症状,提高生活质量,且安全性好。     

丁苯酞注射液对急性大脑中动脉供血区卒中患者的疗效及对脑血管CO2反应性的影响

目的 探讨丁苯酞注射液对急性大脑中动脉供血区卒中患者的疗效及对脑血管CO₂反应性（CO₂R）的影响。方法 选择2014年1月-2017年8月在河南大学附属南阳南石医院神经内科诊治的119例急性大脑中动脉供血区卒中患者,根据治疗方法的不同分为观察组69例与对照组50例。对照组采用常规药物治疗,观察组在对照组基础上联合丁苯酞注射液治疗,两组治疗观察28 d。比较两组临床疗效、简明智力状态检查量表（MMSE）评分、脑梗死体积及脑血管CO₂R变化情况。结果 观察组的总有效率为99.55%,显著高于对照组的88.00%（P<0.05）。治疗后两组的脑梗死体积都较治疗前显著下降（P<0.05）,且观察组显著低于对照组（P<0.05）。两组治疗后的MMSE评分都显著高于治疗前（P<0.05）,且观察组显著高于对照组（P<0.05）。治疗后两组的屏气指数都显著高于治疗前（P<0.05）,且观察组显著高于对照组（P<0.05）。结论 丁苯酞注射液在急性大脑中动脉供血区卒中患者中的应用能改善脑血管CO₂R状况,提高治疗效果与缩小脑梗死体积,促进认知功能的恢复。     

神经节苷脂治疗新生儿缺氧缺血性脑病的疗效和对炎症因子的影响

目的 探究在新生儿缺氧缺血性脑病的治疗中应用神经节苷脂的临床疗效及对血清炎症因子的影响。方法 随机选取上海交通大学医学院附属新华医院2015年2月—2017年2月收治的新生儿缺氧缺血性脑病（HIE）的患儿共54例,并随机分为观察组（n=27）和对照组（n=27）。两组患者均应用同样的基础治疗,对照组患者加用注射用胞磷胆碱钠0.5 g/d,观察组患者则应用神经节苷脂注射液20 mg/d,疗程均为2周。分别比较治疗前后患者的治疗有效率、血气分析结果、血清炎症因子水平和NBNA评分。结果 1个疗程后,观察组患者的治疗有效率（88.9%）显著高于对照组（66.7%）,差异有统计学意义（P<0.05）。治疗前,两组患者的pH值、血氧分压（pO₂）、血二氧化碳分压（pCO₂）和动脉血氧饱和度（SaO₂）无显著差异;治疗后,两组以上各项指标均有显著的改善,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组的pO₂、pCO₂和SaO₂均较对照组显著改善,组间差异有统计学意义（P<0.05）。治疗前,两组患儿白介素-2（IL-2）、白介素-6（IL-6）、超敏C反应蛋白（hs-CRP）和肿瘤坏死因子-α（TNF-α）水平无显著差异。治疗后,两组IL-2的水平较治疗前均有显著升高,IL-6、hs-CRP和TNF-α的水平对比治疗前有显著下降,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组的IL-2水平较对照组显著更高,而IL-6、hs-CRP和TNF-α的水平观察组显著低于对照组,组间差异有统计学意义（P<0.05）。治疗后两组患者评分均有改善,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组的评分显著高于对照组,组间差异有统计学意义（P<0.05）。结论 神经节苷脂治疗HIE患者的疗效确实,对于血清炎症因子水平的升高具有有效的抑制作用,值得临床推广应用。     

B族维生素治疗尿毒症性神经病变的疗效观察

目的 探讨B族维生素治疗尿毒症性神经病变的临床疗效。方法 选取2011年12月—2013年12月在西安市西电集团医院治疗的尿毒症性神经病变患者180例,随机分为治疗组和对照组,每组90例。对照组行维持性血液透析并联合滤过治疗,治疗组患者在对照组基础上给予B族维生素,包括皮下注射维生素B₁₂注射液500 μg/次,肌肉注射维生素B1注射液100 mg/次,2次/周。两组均持续治疗3个月。比较两组患者治疗后神经病变的改善情况。结果 治疗后,两组患者周围神经症状均得到改善,治疗组自发性疼痛、麻木、感觉消退和不安腿综合征的改善率均高于对照组,两组比较差异有统计学意义（P<0.05）。治疗后,两组患者自主神经症状均得到改善,治疗组腹泻、低血压、排汗异常、睡眠障碍的改善率均高于对照组,两组比较差异有统计学意义（P<0.05）。治疗后,两组患者胫神经、正中神经、腓总神经的感觉神经传导速度均有显著提高,同组治疗前后差异有统计学意义（P<0.05）,且治疗后治疗组的改善程度优于对照组,两组比较差异有统计学意义（P<0.05）。结论 B族维生素治疗尿毒症性神经病变有较好的临床疗效,能够改善患者周围神经和自主神经症状,提高感觉神经传导速度,提高患者生存质量,值得临床推广应用。     

布地奈德联合猪肺磷脂注射液对重度新生儿呼吸窘迫综合征患儿肺功能的影响

目的 探讨吸入用布地奈德混悬液联合猪肺磷脂注射液对重度新生儿呼吸窘迫综合征患儿肺功能的影响。方法 选取2016年8月-2018年7月南京市大厂医院收治的重度新生儿呼吸窘迫综合征（NRDS）患儿61例为研究对象,根据随机数字表法分为两组。对照组给予猪肺磷脂注射液联合机械通气治疗,100 mg/kg气管内给药,用药时升温至37℃摇匀,用无菌注射器抽取。观察组在对照组的基础上给予吸入用布地奈德混悬液0.25 mg/kg雾化吸入。比较两组患儿的临床治疗效果、肺功能相关指标及血清铁蛋白（SF）和纤溶酶原激活物抑制剂-1（PAI-1）表达水平。结果 观察组的总有效率为93.55%,高于对照组的73.33%,组间差异有统计学意义（P<0.05）。治疗前两组患儿动脉血氧分压（pO₂）、动脉二氧化碳分压（pCO₂）、吸氧浓度（FiO₂）和氧合指数（OI）无统计学差异;治疗后pO₂和OI显著升高,pCO₂和FiO₂显著下降,同组治疗前后比较差异有统计学意义（P<0.05）;观察组pO₂和OI显著高于对照组,pCO₂显著低于对照组,组间差异有统计学意义（P<0.05）。两组治疗前SF和PAI-1表达水平无统计学差异;治疗后SF和PAI-1均显著降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组低于对照组,差异有统计学意义（P<0.05）。结论 吸入用布地奈德混悬液联合猪肺磷脂注射液可显著降低重度新生儿呼吸窘迫综合征患儿的SF和PAI-1表达水平,改善患儿肺功能,提高临床治疗效果。     

二甲双胍联合炔雌醇环丙孕酮片治疗多囊卵巢综合征的临床研究

目的 探讨二甲双胍联合炔雌醇环丙孕酮片治疗多囊卵巢综合征的临床疗效。方法 选择2010年1月—2014年1月安阳市第三人民医院收治的多囊卵巢综合征患者100例,随机分为治疗组（50例）和对照组（50例）。对照组患者自月经第5天开始口服炔雌醇环丙孕酮片,每晚1片,连服21 d,待撤退性出血第5天开始下一疗程治疗。治疗组在对照组治疗基础上,进餐前30 min口服盐酸二甲双胍片,1片/次,3次/d。两组均连续治疗3个疗程。治疗后,对两组的临床疗效进行评价,同时对两组患者的性激素水平、胰岛素抵抗指数（HOMA-IR）、胰岛素分泌指数（HOMA-β）、排卵率、妊娠率进行比较。结果 治疗组和对照组总有效率分别为96.0%、78.0%,两组比较差异有统计学意义（P<0.05）。治疗后,两组患者的促黄体生成素（LH）、促卵泡生成素（FSH）、睾酮（T）水平均较治疗前显著降低,雌激素（E₂）较治疗前显著升高,同组治疗前后差异有统计学意义（P<0.05）;且治疗后治疗组患者的性激素水平改善程度明显优于对照组,两组比较差异有统计学意义（P<0.05）。治疗后,两组患者HOMA-IR、HOMA-β均较治疗前显著降低,治疗前后比较差异有统计学意义（P<0.05）,且治疗后治疗组这两个指数均低于对照组,两组比较差异有统计学意义（P<0.05）。治疗组排卵率和妊娠率均显著高于对照组,两组比较差异有统计学意义（P<0.05）。结论 二甲双胍联合炔雌醇环丙孕酮片对多囊卵巢综合征有较好的临床疗效,可改善患者的性激素水平,提高患者的妊娠率,值得临床推广应用。     

Fullerene derivatives induce premature senescence: A new toxicity paradigm or novel biomedical applications

Engineered fullerenes (C₆₀) are extensively used for commercial and clinical applications based on their unique physicochemical properties. Such materials have also been recognized as byproducts of many industrial activities. Functionalization of C₆₀ may significantly influence the nature of its interactions with biological systems, impacting its applications and raising uncertainties about its health effects. In the present study, we compared the bioimpact of two chemically modified fullerene derivatives, hexa carboxyl fullerene adduct (Hexa-C₆₀) and tris carboxyl fullerene adduct (tris-C₆₀) to pristine fullerene C₆₀ encapsulated with gamma (γ)-cyclodextrin C₆₀ (CD-C₆₀), using human cutaneous epithelial cells (HEK) to simulate possible applications and occupational dermal exposure route. We report, for the first time, the discovery of premature senescence as a potential endpoint of nanomaterial elicited biological effects, providing a new paradigm for nanoparticle-induced toxicity in human cells. Moreover, this response appeared to be functionalization specific, in that, only tris-C₆₀ induced senescence. We investigated key biological responses, such as cellular viability, intracellular ROS generation, cell proliferation and cell cycle responses. Our results indicate that the often observed ‘anti-apoptotic’ function of fullerene derivatives may be independent of their ‘ROS scavenging’ role as previously reported. We discovered that the tris-C₆₀-induced responses were associated with G₀/G₁ cell cycle arrest and cellular senescence. On further evaluation of the molecular mechanisms underlying the senescent response, a significant decrease in the expression levels of HERC5 was noted. HERC5 is a ubiquitin ligase of the HERC family and is implicated to be involved in innate immune responses to viral and bacterial infections.     

A longitudinal assessment of aflatoxin M1 excretion in breast milk of selected Egyptian mothers.

Aflatoxins are potent toxins and carcinogens which can be excreted in the milk of exposed lactating mothers mainly in the form of aflatoxin M(1) (AFM(1)). We previously evaluated the level and frequency of AFM(1) in breast milk in a group of Egyptian mothers attending the New El-Qalyub Hospital, Qalyubiyah governorate, Egypt. In this study, fifty of those women who were AFM(1) positive were revisited monthly for 12 months to assess the temporal variation in breast milk AFM(1). AFM(1) was detected in 248 of 443 (56%) samples. In a multilevel model of the data there was a highly significant (p<0.001) effect of month of sampling on the frequency of AFM(1) detection with summer months having the highest frequency (>80%) and winter months the lowest frequency (<20%) of detection. AFM(1) was observed most frequently in June [OR 63, 95% CI (7.6, 522)]. The level of AFM(1) detection also followed this seasonal pattern with highest mean level in July (64 pg/ml milk, range 6.3-497 pg/ml milk) and the lowest mean level in January (8 pg/ml milk, range 4.2-108 pg/ml milk). The duration of lactation [p=0.0035, OR=1.08, 95% CI (1.02, 1.13)], and peanut consumption [p=0.06, OR=1.69, 95% CI (0.9, 2.9)] also contributed to the model. The identification and understanding of factors determining the presence of toxicants in human milk is important and may provide a knowledge driven basis for controlling the transfer of chemicals to infants.     

Nimbolide and isonimbolide

Nimbolide 1, a potent molecule of biological significance, was isolated. Attempts were made to cleave the ether linkage in nimbolide using boron trifluoride etherate in the presence of tetrabutyl ammonium bromide so as to generate a ring-opened structure akin to azadirachtins, which are known to possess excellent antifeedant properties. However, a novel rearranged product was envisaged during the course of the reaction, which was determined as isonimbolide 2—a structural isomer of nimbolide through spectroscopic methods.     

In praise of H2O2, the versatile ROS,and its vanadium complexes

Hydrogen peroxide (H₂O₂) is generated in mitochondria in aerobic cells as a minor product of electron transport, is inhibited selectively by phenolic acids (in animals) or salicylhydroxamate (in plants) and is regulated by hormones and environmental conditions. Failure to detect this activity is due to presence of H₂O₂-consuming reactions or inhibitors present in the reaction mixture. H₂O₂ has a role in metabolic regulation and signal transduction reactions. A number of enzymes and cellular activities are modified, mostly by oxidizing the protein-thiol groups, on adding H₂O₂ in mM concentrations. On complexing with vanadate, also occurring in traces, H₂O₂ forms diperoxovanadate (DPV), stable at physiological pH and resistant to degradation by catalase. DPV was found to substitute for H₂O₂ at concentrations orders of magnitude lower, and in presence of catalase, as a substrate for user reaction, horseradish peroxidase (HRP), and in inactivating glyceraldehyde-3-phosphate dehydrogenase. superoxide dismutase (SOD) -sensitive oxidation of NADH was found to operate as peroxovanadate cycle using traces of DPV and decameric vanadate (V₁₀) and reduces O₂ to peroxide (DPV in presence of free vanadate). This offers a model for respiratory burst. Diperoxovanadate reproduces several actions of H₂O₂ at low concentrations: enhances protein tyrosine phosphorylation, activates phospholipase D, produces smooth muscle contraction, and accelerates stress induced premature senescence (SIPS) and rounding in fibroblasts. Peroxovanadates can be useful tools in the studies on H₂O₂ in cellular activities and regulation.     

Prediction of volume of distribution in preclinical species and humans: application of simplified physiologically based algorithms

1. The present study was aimed at developing simplified physiologically based semi-mechanistic algorithms to predict V_ss and interspecies scaling factors to predict tissue-K_ps which require minimum input parameters, diminish the computing complexity and have better predictability.

2. V_ss of 86 structurally diverse compounds in preclinical species and 27 compounds in humans were predicted using only lung- and muscle-K_p as inputs. Interspecies scaling factor (s) were developed based on fold-differences in individual tissue lipid contents, relative organ blood flow: relative organ weight ratio between two species. Tissue-K_ps were predicted for 34 compounds using the newly developed interspecies scaling factors.

3. The predicted-to-experimental V_ss values for all the 113 compounds was 1.3?±?0.9 with 83% values being within a factor of two. The tissue-K_ps in rat, dog and human were predicted using experimental tissue-K_p data in rodents and interspecies scaling factors and here also, 83% of tissue-K_ps were within two-fold of the experimental values.

4. In conclusion, simplified physiologically based algorithms have been developed to predict both volume of distribution and tissue-K_ps, in which required input parameters as well as computing complexity have been noticeably reduced.

     

维生素D原体浓度对它的光异构反应的影响

目的：研究乙醇溶液中维生素D原体浓度对它的光异构反应产物产率的影响。方法：用两种紫外光激发光源光照不同浓度的维生素D原体乙醇溶液，使用正相HPLC系统定量测定主要光异构物在溶液中的浓度。结果：数据表明，随维生素D原体浓度的增加，速甾醇产率减少，而光甾醇产率明显增加。维生素D前体产率变化，与所用的激发光源有关。结论：维生素D原体浓度对其光异构反应产物产率的影响较大，特别对速甾醇和光甾醇，利用光自吸收效应有助于设计光化学法合成药物及制备高产率的光异构产物。     

Serotonergic approaches in the development of novel antipsychotics

Schizophrenia is a chronic, debilitating neuropsychological disease characterised by positive, negative, and cognitive deficits. In recent years, new pharmacological treatment strategies have been developed to treat the sequalae of schizophrenia based upon more selective receptor activity profiles in the hope that treatment efficacy can be increased without inducing the side-effect profiles seen with current available therapies. One such strategy involves the development of combined (partial) 5-HT_1A agonists and D₂ receptor (partial) antagonists such as bifeprunox, SLV313, F15063 and SSR-181507 in an attempt to increase therapeutic efficacy of all symptom domains whilst alleviating adverse side effects. Other novel drugs including SLV310 and SLV314 combine selective serotonin reuptake inhibition (SSRI) functionality with D₂ receptor antagonism in an attempt to not only improve schizophrenic symptoms, but to also relieve other affective disorders intricately linked with the disorder. The main scope of this review will evaluate the major preclinical and clinical pharmacological findings concerning the aforementioned strategies and pharmacological agents, and compare their therapeutic potential with currently available antipsychotics; however, recent developments at other emerging serotonergic targets such as 5-HT_2C, 5-HT₆ and 5-HT₇ receptors will also be considered.     

Urinary biomarkers of aflatoxin exposure in young children from Egypt and Guinea.

Aflatoxins are a major risk factor for hepatocellular carcinoma (HCC), and thus understanding the pattern of aflatoxin exposure in different regions is important in order to develop targeted intervention strategies. Given the early onset of HCC in many countries early life exposures may be important. This study investigated aflatoxin exposure in Egyptian children (n=50, aged 1-2.5 years) by assessing urinary aflatoxin metabolite (AFM(1), AFB(1), AFB(2), AFG(1), AFG(2)) levels. Samples from Guinean children (n=50, aged 2-4 years) were analyzed in parallel providing a comparison to a region of established frequent aflatoxin exposure. Aflatoxins were isolated from urine using C18-cartridges followed by immunoaffinity clean-up, and quantified by HPLC with fluorescence detection. Overall aflatoxins were less frequently present in Egyptian (38%) than Guinean urine samples (86%) (p<0.001), which was particularly related to differences in detection rates of AFM(1) (8% compared to 64%, respectively, (p<0.001)). For AFM(1) the geometric mean level in Guinea (16.3 pg/ml; 95% CI: 10.1, 26.6 pg/ml) was 6-fold higher (p<0.001) than in Egypt (2.7 pg/ml; 95% CI: 2.5, 2.8 pg/ml). Urinary aflatoxins from healthy children in these two regions have not previously been reported, and exposure appears modest in Egypt compared to Guinea. These data suggest that measures to reduce aflatoxin exposure in both regions are important, though particularly in Guinea.     

Integrin antagonists as therapeutics for inflammatory diseases

Integrins are a family of heterodimeric cell surface receptors that mediate adhesion events crucial to cellular migration, proliferation and activation. Although critical to a normal immune response, integrins can also facilitate the progression of many inflammatory and autoimmune disorders. As such, they have attracted the attention of the pharmaceutical industry. Several humanised monoclonal antibodies directed against integrin targets have proven to be successful in clinical trials and have been approved for use in humans. This has not only resulted in effective therapies for patients, but also has provided important proof-of-concept studies for the development of small-molecule antagonists. This review focuses on those integrin subclasses that are being evaluated for their potential role in pulmonary, dermatological, gastrointestinal or rheumatic diseases. These include the α₄ and β₂ integrins, as well as an emerging group of targets from the collagen-binding family of integrins. Interfering with integrin signalling pathways represents a future area of interest. The rationale for pursuing these targets, as well as the drugs presently under development, are discussed.