发作性睡病的药物治疗进展

发作性睡病是致残性白天睡眠增多的最常见原因之一，其治疗旨在减少白天睡眠增多和猝倒，改善夜间睡眠紊乱、睡眠瘫痪及与睡眠有关的幻觉。2019年，组胺H3受体拮抗剂替洛利生（Pitolisant）和多巴胺及去甲肾上腺素再摄取抑制剂索利氨酯（Solriamfetol）分别在欧盟和美国上市，前者具有促醒和抗猝倒作用，后者也有促醒作用，且戒断症状和滥用的发生率更低。目前，控释型羟丁酸钠（FT218）、低钠型羟丁酸盐（JZP-258）、选择性去甲肾上腺素再摄取抑制剂（瑞波西汀，又称AXS-12）以及莫达非尼联合氟卡尼制剂（THN102）等药物仍在开发和测试中，均可作为治疗发作性睡病相关白天睡眠增多和猝倒的潜在药物。本文重点介绍这些最近研发的发作性睡病治疗药物。     

疏肝和中汤联合雷贝拉唑治疗肝胃郁热型反流性食管炎临床研究

的:探讨疏肝和中汤联合雷贝拉唑治疗肝胃郁热型反流性食管炎患者的疗效。方法:选择68 例肝胃郁热型反流性食管炎患者,随机分为治疗组和对照组,每组34例。对照组给予雷贝拉唑治疗; 治疗组给予疏肝和中汤联合雷贝拉唑治疗,8周为1个疗程,随后观察患者治疗前后的症状积分变化及食管黏膜修复作用,及其对胃蛋白酶原I(PGI)、胃蛋白酶原比值(PGR)、胃泌素17(G-17)水平影响,评价两组药物的临床疗效。结果: 治疗组临床疗效总有效率91.2%; 对照组临床疗效总有效率70.1%,经统计学分析具有统计学意义,治疗组疗效优于对照组(P<0.05)。 中药对改善嘈杂易饥、神疲乏力、抑郁或心烦易怒、口苦咽干、大便秘结等肝胃郁热症状效果优于对照组。 中药组能更好促进食管黏膜修复作用,达到良好效果。 疏肝和中汤联合雷贝拉唑可以降低胃蛋白酶原I(PGI)、胃蛋白酶原比值(PGR)、胃泌素17(G-17)水平。结论:疏肝和中汤联合雷贝拉唑对反流性食管炎肝胃郁热证具有较好的临床疗效。     

丙戊酸钠治疗对血清瘦素、体重指数的影响

目的服用丙戊酸钠(VPA)抗癫痫治疗的患者,15%～70%的成人可发生体重增加[1-2],而瘦素在体重和能量平衡的调节中起重要影响,近年来许多研究表明VPA引起的体重改变可能与瘦素有关。探讨丙戊酸钠抗癫痫治疗对血清瘦素的影响,该影响与患者体重改变的相关性,以及瘦素的可能机制。方法以丙戊酸钠治疗超过3个月的33例癫痫患者为治疗组,20例未经丙戊酸钠治疗癫痫患者作为对照组来比较,检测患者体重、身高、血清瘦素水平,比较两组的体重指数(BMI)、血清瘦素水平。结果丙戊酸钠治疗组的血清瘦素(8.8503±4.7924)ug/ml与对照组(2.8490±1.3962)ug/ml比较有增高,治疗组BMI(23.7202±2.5182)高于对照组(20.8468±1.6815)。结论丙戊酸钠治疗可能引起血清瘦素、体重指数增高,很可能通过诱导导致瘦素抵抗的机制之一,从而导致患者体重增加。     

Food preservatives sodium sulfite and sorbic acid suppress mitogen-stimulated peripheral blood mononuclear cells

Antioxidant preservatives prolong the quality of food and ensure the nutritional adequacy, palatability and safety of many processed foods and beverages. Effects of sodium sulfite (E221) and sorbic acid (E200) were investigated in human peripheral blood mononuclear cells (PBMC) which were purified from blood of healthy donors. Cells were stimulated with the mitogen phytohaemagglutinin in vitro, which induces proliferation of T-cells and the production of Th1-type cytokines like interferon-γ. The latter triggers enzyme indoleamine (2,3)-dioxygenase, which degrades tryptophan, and GTP cyclohydrolase I, which leads to increased neopterin production, in monocyte-derived macrophages. Sodium sulfite and sorbic acid suppressed both these biochemical changes in a dose-dependent way (P < 0.01 at 1 mM sodium sulfite and 50 mM sorbic acid). Data demonstrate a suppressive influence of sodium sulfite and sorbic acid on the activated Th1-type immune response.     

雷贝拉唑与兰索拉唑三联疗法治疗幽门螺杆菌阳性消化性溃疡疗效比较

目的:比较雷贝拉唑三联疗法与兰索拉唑三联疗法治疗幽门螺杆菌阳性消化性溃疡的疗效。方法:将幽门螺杆菌阳性的消化性溃疡83例分为两组:治疗组(雷贝拉唑三联疗法组)41例,以雷贝拉唑10mg,阿莫西林1000mg及甲硝唑400mg每日2次口服,治疗1周后单独服用雷贝拉唑10mg,连服7d;对照组(兰索拉唑三联疗法组)42例:以兰索拉唑30mg,阿莫西林1000mg及甲硝唑400mg,每日2次口服,治疗1周后单独服用兰索拉唑30mg,连服7d。治疗期间每周门诊随诊,记录临床症状改善情况,用药结束1个月后复查胃镜并检测幽门螺杆菌结果。结果:治疗组和对照组1d的临床症状缓解率分别为80%、60%,差异有统计学意义(P<0.05);1周后症状缓解率均为98%。治疗组和对照组的溃疡愈合率分别为93%和76%,差异有统计学意义(P<0.05);治疗组和对照组的总有效率分别为98%和96%,差异无统计学意义(P>0.05)。治疗组和对照组的幽门螺杆菌根除率分别85%和81%,差异无统计学意义(P>0.05)。结论:两组方案均能有效治疗消化性溃疡和缓解临床症状,并能有效地根除幽门螺杆菌。但雷贝拉唑三联疗法在改善临床症状和促进溃疡愈合方面优于兰索拉唑三联疗法。     

透明质酸钠对大鼠成肌细胞增殖和分化的影响

目的 研究透明质酸钠对成肌细胞增殖和分化的影响。方法 采用酶消化法将新生SD大鼠骨骼肌组织分离、纯化、原代培养及传代培养；取第3代成肌细胞，分别加入浓度为0．05%、0．1％及0．2％的透明质酸钠溶液作为生长培养基行体外培养为实验A、B及C组，加入常规生长培养基为对照D组，观察各组成肌细胞增殖情况，并采用细胞计数及MTT法绘制生长曲线。另选择0．1%透明质酸钠融合培养基行体外成肌细胞培养，常规融合培养基作对照，观察透明质酸钠对成肌细胞分化功能的影响。结果A、B及C组成肌细胞增殖表现相似，2d时进入对数生长期，4d时均达顶峰；D组成肌细胞于3d时进入对数生长期，5d时细胞数倍增，6d时达顶峰。MTT法所测吸光度（A）值的变化反映成肌细胞的增殖情况，与细胞计数的结果一致，以B组细胞增殖作用最明显，B组A值在2～8d时均高于C、D组（P〈0．05），8d时高于A组（P〈0．05）。0．1％透明质酸钠融合培养基中的成肌细胞融合率较低且上升缓慢，7d时融合率最高，为11．7％；常规融合培养基成肌细胞融合率于6d时达到峰值，约为35．0%。结论 透明质酸钠与成肌细胞的细胞相容性较好，可以作为良好的成肌细胞培养基。     

透明质酸钠与带蒂筋膜脂肪片预防椎管粘连157例临床观察

目的:讨透明脂酸钠与带蒂筋膜脂肪片联合应用预防椎管粘连的可行性。方法:板切除减压,病灶摘除后,将透明脂酸钠2～4ml注入硬膜周围,后用带蒂筋膜脂肪片覆盖椎版缺损处。结果:57例术后随访6～64个月,优良率98%。结论:明脂酸钠与带蒂筋膜脂肪片联合应用为预防椎管粘连的有效方法。     

Dopaminergic transmission in the hypothalamic arcuate nucleus to produce acupuncture analgesia in correlation with the pituitary gland

Acupuncture analgesia (AA) caused by low frequency stimulation of the acupuncture point (AP) was abolished by hypophysectomy and adrenalectomy. Termination of the AA producing pathway from the AP to the pituitary gland was in the medial hypothalamic arcuate nucleus (M-HARN). The origin of the descending pain inhibitory system associated with AA was in the posterior HARN (P-HARN). AA in the hypophysectomized rats, and enhanced neuronal activity in the P-HARN that were abolished during acupuncture stimulation, were both restored by intraperitoneal microinjection of 0.5 mg/kg morphine or 0.1 micrograms beta-endorphin into the P-HARN during acupuncture stimulation. Of the analgesia produced by dopamine or beta-endorphin injected into the P-HARN, that caused by beta-endorphin disappeared after denervation of the M-HARN. The P-HARN neurons that responded to acupuncture stimulation also responded to iontophoretic dopamine, but not to iontophoretic morphine nor ultramicroinjected beta-endorphin. The transmission between the M-HARN and P-HARN may be dopaminergic, and beta-endorphin might presynaptically modulate this transmission. Reduction of sodium ions may have been the reason for abolition of AA after adrenalectomy.     

Buffering the stomach content enhances the absorption of diflunisal in man

Diflunisal, a lipophilic salicylate, is absorbed more slowly in healthy volunteers than aspirin. In this paper we report on attempts to influence diflunisal absorption by buffering the gastric milieu. Sodium bicarbonate given together and 30 min after diflunisal tablets significantly (p less than 0.05) shortened the time to reach peak plasma concentration (tmax greater than 15 per cent), raised maximum plasma concentration slightly (Cmax 6 per cent) and increased the area under the plasma concentration-time curve (AUC greater than 8 per cent). Other pharmacokinetic parameters, including terminal half-life and renal elimination of the compound, were not considerably influenced. These findings indicate that the absorption of diflunisal was enhanced by increased gastric pH, presumably a result of an increased solubility of diflunisal in the stomach together with faster transport into the small intestine. In one volunteer, after intravenous administration diflunisal plasma concentrations declined in a triphasic manner with a terminal half-life of 12.8 h. The volume of distribution was approximately 10 per cent of body weight. Based on the ratio of AUC after equivalent i.v. and oral diflunisal doses, the absolute bioavailability was 89.5 per cent.     

NariSO3和NaCl联合增敏光度法测定碘盐中微量碘

研究亚硫酸氢钠和氯化钠配伍使用的增敏性,建立了NaHSO3—NaCl—KIO3—KI四元无机体系测定碘盐中碘含量的新方法。测定碘的最佳条件:磷酸介质,pH 3~4,最大吸收波长479 nm,ε479=1.5×105L/(mol/cm),碘含量(以KIO3中I计)在0~2.24mg/L内符合比尔定律。用于测定食盐中碘的含量,回收率为99.49%~101.3%,结果满意。