Role of NADPH-cytochrome P450 reductase and cytochrome-b5/NADH-b5 reductase in variability of CYP3A activity in human liver microsomes

NADPH-cytochrome P450 reductase (CPR) and cytochrome-b(5) (b(5)) together with NADH-b(5) reductase (b(5)R) play important roles in cytochrome P450 3A-mediated drug metabolism via electron transfer. However, it is not clear whether variability in expression of these accessory proteins contributes to the known interindividual variability in CYP3A activity. CPR and b(5) were measured in human liver microsomes (HLMs) by spectrophotometry and immunoblotting. HLMs from elderly (>or=46 years) male donors (n=11) averaged 27% (P=0.034) and 41% (P=0.011) lower CPR levels than young (相似文献   

IMAGING LUNG AERATION AND LUNG LIQUID CLEARANCE AT BIRTH USING PHASE CONTRAST X-RAY IMAGING

• 1 The transition to extra‐uterine life at birth is critically dependent on airway liquid clearance to allow the entry of air and the onset of gaseous ventilation. We have used phase contrast X‐ray imaging to identify factors that regulate lung aeration at birth in spontaneously breathing term and mechanically ventilated preterm rabbit pups.
• 2 Phase contrast X‐ray imaging exploits the difference in refractive index between air and water to enhance image contrast, enabling the smallest air‐filled structures of the lung (alveoli; < 100 µm) to be resolved. Using this technique, the lungs become visible as they aerate, allowing the air–liquid interface to be observed as it moves distally during lung aeration.
• 3 Spontaneously breathing term rabbit pups rapidly aerate their lungs, with most fully recruiting their functional residual capacity (FRC) within the first few breaths. The increase in FRC occurs mainly during individual breaths, demonstrating that airway liquid clearance and lung aeration is closely associated with inspiration. We suggest that transpulmonary pressures generated by inspiration provide a hydrostatic pressure gradient for the movement of water out of the airways and into the surrounding lung tissue after birth.
• 4 In mechanically ventilated preterm pups, lung aeration is closely associated with lung inflation and a positive end‐expiratory pressure is required to generate and maintain FRC after birth.
• 5 In summary, phase contrast X‐ray imaging can image the air‐filled lung with high temporal and spatial resolution and is ideal for identifying factors that regulate lung aeration at birth in both spontaneously breathing term and mechanically ventilated preterm neonates.

     

Gait training improves performance in healthy adults exposed to novel sensory discordant conditions

Recent evidence shows that the ability to adapt to a novel discordant sensorimotor environment can be increased through prior training. We aimed to determine whether gait adaptability could be increased and then retained using a training system comprised of a treadmill placed on a motion base facing a virtual visual scene that provided a variety of sensory challenges that served as training modalities. Ten healthy adults participated in three training sessions during which they walked on a treadmill at 1.1 m/s while receiving discordant support-surface and visual manipulations. Upon completion, participants were presented with a novel sensorimotor challenge designed to test for transfer of adaptive skills. During this test, stride frequency, reaction time, and heart rate data were collected as measures of postural stability, cognitive load, and anxiety, respectively. Compared to 10 untrained controls, trained participants showed enhanced overall performance on the Novel Test, which was administered 20 min after their final training session. Subjects in both groups had greater stride frequency, reaction time, and heart rate when exposed to the new sensory environment; however, these increases were less pronounced in the trained subjects than in the controls. The Novel Test was re-administered to both groups 1 week, 1 month, 3 months, and 6 months later. Trained subjects maintained their level of performance for 6 months. Untrained subjects continued to improve in these measures at each subsequent test session, suggesting that a lasting sensorimotor adaptability training effect can be achieved with very short, repeated exposures to discordant sensory conditions.     

Monitored naltrexone without counseling for alcohol abuse/dependence in schizophrenia-spectrum disorders

This clinical trial assessed the effects of monitored naltrexone treatment in 19 subjects with schizophrenia spectrum and alcohol use disorders in an eight-week prospective open pilot study. Naltrexone was directly administered to subjects in oral doses of 100 mg on Mondays and Wednesdays, and 150 mg on Fridays. Subjects received reimbursement for attending the three weekly study visits. Subjects continued to receive their usual psychiatric care with no added alcohol counseling provided. Alcohol use was assessed by self-report and biomarkers. Psychosis severity was measured by the Positive and Negative Syndrome Scale (PANSS). Subjects reported significant reductions in their number of drinks per week, drinks per drinking day, days of drinking to intoxication, and alcohol craving. Subjects also showed significant reductions in Addiction Severity Index (ASI) alcohol composite scores and in PANSS positive, negative and general psychopathology scores.     

失语症的康复治疗

目的:综述失语症的类型及其康复治疗现状,为促进失语症患者言语功能的恢复提供一定的理论依据和实践指导。资料来源:应用计算机检索中国期刊网1994-01/2006-04有关失语症和言语治疗的文献,检索词“失语症、言语治疗、康复”,并限定文章的语言种类为中文。同时手工检索相关书籍。资料选择:对资料进行初审,选取试验包括采用Schuell刺激法、旋律语调治疗、实用交流训练等治疗组和对照组的命名、阅读、听理解、复述变化比较的相关文献,删除明显不随机临床试验的研究,然后查找余下的文献全文,进一步判断是否为随机对照实验。质量评价主要考察资料的真实性,调查设计是否严密,实施过程是否严格,统计学处理是否合理。资料提炼:共检索45篇关于失语症的康复治疗文献,30篇符合纳入标准,排除的15篇为重复研究。资料综合:根据国内外通用的解剖-临床相关基础分类,失语症的类型主要有8种:Broca失语、Wernicke失语、传导性失语、经皮质运动性失语、经皮质感觉性失语、经皮质混合性失语、完全性失语、命名性失语。失语症康复治疗方法主要包括语言治疗技术、功能性交流治疗、认知神经康复治疗、社交心理治疗、计算机辅助治疗等。结论:失语症类型多样,应针对言语功能障碍选择适宜的言语康复治疗方法,或采用综合的治疗措施,这有利于提高失语症的治疗效果。     

家兔慢性冬眠心肌模型的建立

目的:建立家兔慢性心肌冬眠模型。RA方法:实验于2006-02/12在福建省冠心病研究所完成。实验分组:选择健康家兔30只,按随机数字表法分为模型组(n=18)和假手术组(n=12)。模型组采用开胸不全结扎冠状动脉左前降支中段,关胸后继续喂养1个月,造成心肌慢性缺血,构建家兔慢性冬眠心肌模型。假手术组仅开胸不作冠状动脉左前降支中段结扎。实验评估:①采用冠状动脉造影观察冠状动脉左前降支中段狭窄程度。②超声心动图、多巴酚丁胺超声心动图负荷实验观察慢性缺血心肌室壁运动情况。③氯化三苯基四氮唑染色检测心肌坏死程度。④苏木精-伊红常规染色利用光学显微镜观察心肌组织结构变化。⑤苦味酸-天狼猩红胶原纤维染色观察心肌间质胶原纤维增生情况。结果:术后模型组家兔15只和假手术组12只进入结果分析。①狭窄程度:模型组冠状动脉左前降支中段直径平均狭窄率为(84.90±4.24)%,假手术组未见明显狭窄。②左心室整体收缩功能:模型组左室射血分数、短轴缩短率显著低于假手术组,差异有显著性意义(t=10.314,11.938,P<0.01)。③心肌室壁运动情况:静息时模型组左室壁异常运动节段47个。多巴酚丁胺超声心动图负荷实验34个节段出现室壁运动障碍程度先加重而后改善的典型冬眠心肌的双相反应。④心肌坏死程度:氯化三苯基四氮唑染色显示模型组3只家兔出现小灶性透壁心肌坏死,其余12只家兔均未发现心肌坏死。假手术组12只家兔均未发现心肌坏死。⑤心肌组织结构变化:苏木精-伊红染色显示模型组心肌纤维肿胀,染色不均匀,横纹模糊,核周水肿;假手术组心肌纤维排列整齐、连接紧密。⑥心肌间质胶原纤维增生情况:苦味酸-天狼猩红胶原纤维染色显示模型组心肌间质、血管周围可见大量胶原纤维,呈不规则网状或团块状;假手术组心肌间质、血管周围见零星分布的胶原纤维。结论:采用开胸不全结扎冠状动脉左前降支中段建立家兔慢性心肌冬眠模型是可行的。     

Surgical hypothermia in a patient with a cold agglutinin. Management by plasma exchange

Cold agglutinins are a potential danger to patients who must be subjected to hypothermia. A patient with a cold agglutinin of moderate titer but broad thermal amplitude was to undergo hypothermia during aortic valve replacement. He was managed preoperatively with an eight- liter plasma exchange by continuous-flow centrifugation to remove the cold agglutinin. There were no adverse effects during or after hypothermia.     

不同产地和品种淫羊藿中淫羊藿苷的HPLC分析

目的 :对中药淫羊藿中淫羊藿苷的含量分析进行方法学研究 ,并测定淫羊藿的不同产地、不同品种、不同药用部位的淫羊藿苷的含量。方法 :采用RP HPLC技术对 7个品种 2 3个样品进行测定。以PERKIN EIMER SH/5C18柱为分析柱 ,流动相为乙腈 水 36%乙酸 ( 2 5∶73.5∶1 .5)流速 1 .0ml/min。UV检测波长 2 70nm。结果 :本方法测定淫羊藿苷含量在 0 .0 2 1 2～ 0 .1 2 7μg ,0 .53～ 1 .696μg范围内呈良好的线性关系。不同产地、不同品种、不同药用部位的淫羊藿其淫羊藿苷的含量为 0 .0 0 30 7%～ 1 .55%。同一植株不同部位中淫羊藿苷的含量分布叶 >叶茎 >茎 >根。结论 :淫羊藿由于产地不同、品种不同其淫羊藿苷的含量相差悬殊。本测定方法为筛选优良品种和扩大药源提供了简便易行的方法     

国产尼莫地平片和尼莫通片的生物利用度比较

国产尼莫地平片和尼莫通片的生物利用度比较施孝金王宏图韦阳张静华张莉莉钟明康（上海医科大学华山医院临床药学研究室，上海２０００４０）钙离子通道拮抗剂尼莫地平（ｎｉｍｏｄｉｐｉｎｅ，ＮＭ），临床上主要用于治疗有明显症状的老年性脑功能损伤和由于蛛网膜下腔出...