氟哌噻吨和美利曲辛合剂治疗伴有抑郁和/或焦虑症状紧张性头痛的研究

目的:探索治疗伴有抑郁和/或焦虑状态紧张性头痛的有效方法,以及抗抑郁/焦虑药物在治疗该类紧张性头痛中的作用。方法:将伴有抑郁和/或焦虑状态的紧张性头痛患者138例随机分为2组,即氟哌噻吨和美利曲辛合剂(黛力新)及头痛发作时加用散立痛组(治疗组,最终完成57例)和头痛发作时单用散立痛组(对照组,最终完成52例),进行随机单盲对照研究,同时用汉密尔顿抑郁量表评分(HAMD)和汉密尔顿焦虑量表评分(HAMA)对其抑郁和/或焦虑状况进行治疗前及治疗后(第2,4,6周)的评估。结果:治疗组头痛每月发作天数显著减少(第2周P<0.05,第4,6周P<0.01),头痛发作持续时间缩短(第2,4,6周均P<0.01);同时HAMD及HAMA均显著减少(第2,4,6周均P<0.01)。结论:对于伴有抑郁和/或焦虑状态的紧张性头痛患者,除应用对症治疗外,应该加用抗抑郁/焦虑药物。     

黛力新辅助治疗伴有抑郁和（或）焦虑状态慢性紧张型头痛30例

目的 探索伴有抑郁和（或）焦虑状态慢性紧张型头痛（CTH）的有效治疗方法.方法 将符合入选标准的60例患者随机分为2组各30例.治疗组用黛力新、复方氯唑沙宗和硫必利,对照组仅用复方氯唑沙宗和硫必利,疗程均为6周;于治疗前及治疗后2,4,6周末记录前1周头痛发作次数、持续时间和头痛程度,同时用汉密尔顿抑郁量表（HAMD）和汉密尔顿焦虑量表（HAMA）评分.结果 治疗组头痛发作次数显著减少,头痛程度显著减轻,头痛发作持续时间缩短(P＜0.05或P＜0.01),同时能显著减少HAMD及HAMA评分(P＜0.05或P＜0.01).结论 对伴有抑郁和（或）焦虑状态的CTH患者,联合应用黛力新,治疗效果较单用复方氯唑沙宗和硫必利好.     

盐酸舍曲林治疗伴有抑郁或焦虑的偏头痛患者临床分析

目的探索治疗偏头痛伴有抑郁和/或焦虑患者的有效方法,研究抗抑郁/焦虑药物是否比头痛发作时单用镇痛药物疗效更佳。方法将88例伴有抑郁和/或焦虑的偏头痛患者随机分为2组,治疗组48例,用盐酸舍曲林＋尼美舒利分散片（非甾体抗炎药）治疗,对照组40例,用尼美舒利分散片治疗,并进行随机单盲对照研究,同时用汉密尔顿抑郁量表评分（HAMD）和汉密尔顿焦虑量表评分（HAMA）,对其抑郁和/或焦虑进行治疗前及治疗后（第4、8周）的评估。结果治疗组患者头痛发作次数显著减少（第4周P〈0.05,第8周P〈0.01）,头痛程度显著减轻（第4周P〈0.05,第8周P〈0.01）,头痛发作持续时间缩短（第4、8周均P〈0.01）;同时能显著减少HAMD（第4、8周均P〈0.01）及HAMA（第4、8周均P〈0.01）。结论伴有抑郁和/或焦虑的偏头痛患者,除对症治疗外,可以合并应用盐酸舍曲林。     

帕罗西汀联合氟桂利嗪治疗伴情绪障碍的偏头痛69例

目的 观察帕罗西汀与氟桂利嗪联合治疗伴焦虑、抑郁情绪的偏头痛患者的疗效与不良反应.方法 将138例伴情绪障碍的偏头痛患者随机均分为两组,治疗组给予帕罗西汀和氟桂利嗪口服,对照组单用氟桂利嗪,均以6周为1个疗程,根据治疗前后头痛发作次数、持续时间及头痛严重程度的变化进行疗效评定,并用汉密尔顿抑郁量表(HAMD)和汉密尔顿焦虑量表(HAMA)进行评分.自制副反应量表记录不良反应.结果 两种治疗方法均可显著减少偏头痛发作次数,缩短头痛发作时间,减轻头痛程度(P<0.01);治疗组还可明显减轻患者的抑郁焦虑症状,治疗后2,4,6周HAMD和HAMA评分的改善优于对照组(P<0.01);治疗组头痛持续时间的缩短也优于对照组(P<0.01).结论 帕罗西汀联合氟桂利嗪治疗伴有情绪障碍的偏头痛有较好疗效,不良反应不需作特殊处理.     

黛力新联合西比灵治疗偏头痛伴焦虑抑郁症状的疗效观察

目的探讨黛力新联合西比灵治疗偏头痛伴焦虑抑郁情绪的临床疗效。方法将66例伴抑郁和焦虑情绪的偏头痛患者随机分为治疗组和对照组组,治疗组给予黛力新与西比灵治疗,对照组单用西比灵治疗,治疗6周后进行疗效评定,并用汉密尔顿抑郁量表(HAMD)和汉密尔顿焦虑量表(HAMA)进行抑郁和焦虑情绪评价。结果两组治疗后发作次数、持续时间均明显低于治疗前(P<0.05),且治疗后,治疗组发作次数及持续时间均明显低于对照组(P<0.05);两组治疗后疼痛程度均明显降低(P<0.05),且治疗后,观察组头痛缓解程度优于对照组(P<0.05)。治疗后,两组HAMD及HAMA评分均明显低于治疗前(P<0.05),治疗组治疗后HAMD及HAMA评分均明显低于对照组(P<0.05)。结论黛力新联合西比灵治疗伴焦虑抑郁情绪的偏头痛疗效显著,对头痛症状和情绪障碍均有较好的改善作用。     

右佐匹克隆联合氟哌噻吨/美利曲辛治疗失眠伴发抑郁和(或)焦虑状态的疗效观察

目的探讨右佐匹克隆联合氟哌噻吨/美利曲辛(商品名黛力新)治疗失眠伴有抑郁和(或)焦虑状态患者的有效性及安全性。方法 150例失眠伴有抑郁和(或)焦虑状态的患者随机分为右佐匹克隆联合黛力新组、单用黛力新组、单用右佐匹克隆组,每组50例,疗程8周。用匹茨堡睡眠质量指数量表(PSQI)、汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)评定疗效,用治疗中出现的症状量表(TESS)及8周末实验室检查评定治疗的安全性。结果在治疗第8周末与治疗前比较,右佐匹克隆组和黛力新组PSQI显著下降(P<0.05),合用药组PSQI极显著下降(P<0.01),右佐匹克隆组的HAMD、HAMA评分无显著下降(P>0.05),黛力新组和合用药组的HAMD、HAMA评分均明显下降(P<0.01)。治疗后3组间比较,合用药组PSQI评分显著低于右佐匹克隆组和黛力新单用药组(P<0.05),黛力新组和合用药的HAMD、HAMA评分比较差异无统计学意义(P>0.05),黛力新组和合用药的HAMD、HAMA评分均显著低于右佐匹克隆组(P<0.01)。3组间不良反应差异无统计学意义(P>0.05)。结论右佐匹克隆联合黛力新治疗失眠伴发的抑郁、焦虑疗效好,耐受性好,且无明显不良反应。     

乙哌立松联合艾司西酞普兰对伴抑郁和(或)焦虑紧张型头痛的临床疗效

目的:探讨乙哌立松联合艾司西酞普兰对伴抑郁和(或)焦虑的紧张型头痛(tension-type headaehe,TTH)的有效性及安全性。方法:选取2014年1月至2017年12月在福建医科大学附属漳州市医院神经内科门诊就诊的伴抑郁和(或)焦虑TTH患者606例作为研究对象,按照随机数字表法随机分为单药组(艾司西酞普兰治疗)285例和联合组(乙哌立松联合艾司西酞普兰治疗)321例。治疗8周,用疼痛视觉模拟评分(VAS)卡尺、汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)评定疗效和安全性。结果:单药组及联合组患者同组内治疗前后的VAS、HAMD、HAMA评分比较,差异均有统计学意义(P<0.01);治疗8周后,联合组的VAS、HAMD、HAMA评分与单药组比较,差异均有统计学意义(P<0.01)。结论:乙哌立松联合艾司西酞普兰对伴抑郁和(或)焦虑状态的TTH疗效显著,在改善头痛和抑郁、焦虑情绪方面的疗效均优于单用艾司西酞普兰治疗,耐受性好,无明显不良反应。     

帕罗西汀治疗伴情绪障碍的偏头痛

目的：探讨帕罗西汀治疗伴有情绪障碍的偏头痛的临床疗效。方法：将偏头痛病人127例分为2组,帕罗西汀组68例[男性26例,女性42例,年龄(30±s 12)a,13～74 a],口服帕罗西汀20 mg,每早1次,1 wk后加至40 mg,每早1次,头痛缓解1wk后给予维持量10mg,每早1次；硫必利组59例[男性24例,女性35例,年龄(30±18)a,15～68 a],入院后即给予硫必利100mg,每日3次,维持量为50 mg,每日2～3次,均6wk为一个疗程。进行对照研究,用汉密尔顿抑郁量表(HAMD)和汉密尔顿焦虑量表(HAMA)对其抑郁焦虑状态进行治疗前及治疗后(wk 2,4,6)评估。结果：帕罗西汀组和硫必利组不仅可以明显减轻病人的抑郁焦虑症状,还可以显著减轻偏头痛发作次数,缩短头痛发作的时间(P＜0．01)；帕罗西汀组总有效率96%(65/68),硫必利组总有效率81%(48/59),2组疗效比较,经Ridit分析有显著差异(P＜0．05)。结论：帕罗西汀治疗伴有情绪障碍的偏头痛有较好疗效。     

阿米替林治疗紧张型头痛的疗效观察

目的观察阿米替林对伴或不伴抑郁和/或焦虑状态紧张型头痛患者的疗效。方法诊断为紧张型头痛患者92例,行汉密尔顿抑郁量表(HAMD)和焦虑量表(HAMA)评分后随机分为阿米替林组和对照组,治疗后根据头痛程度、HAMD、HAMA评分变化,判断疗效及副反应。结果阿米替林治疗2、4、6W后患者头痛明显减轻与治疗前相比有极显著的差异(P<0.01);对照组无差异(P>0.05)。阿米替林治疗2、4、6周时与治疗前比较HAMD、HAMA评分明显降低(P<0.01),对照组治疗2、4、6周时HAMD、HAMA无明显变化(P>0.05)。小剂量递增阿米替林出现口干、恶心、嗜睡等不适症状轻,易接受。结论紧张型头痛患者采用阿米替林小剂量递增方法可达到有效治疗目的,具有起效快、效果确切、价格实惠的优点。     

养血清脑颗粒与多塞平治疗紧张性头痛的比较

目的 :观察养血清脑颗粒对紧张性头痛伴抑郁和 (或 )焦虑症状患者的治疗效果及安全性。方法 :对应用汉密尔顿抑郁量表 (HAMD)和汉密尔顿焦虑量表 (HAMA)确诊的紧张性头痛伴抑郁和 (或 )焦虑症状患者随机分为养血清脑颗粒组和多塞平组 ,治疗后根据头痛强度、HAMD、HAMA评分判断疗效和副作用。结果 :养血清脑颗粒组治疗 2周时头痛强度、HAMD、HAMA与治疗前比较评分减少 (P <0 .0 5 ) ,治疗 4周时评分明显减少 (P <0 .0 1) ,多塞平治疗 2周、4周时头痛强度、HAMD、HAMA与治疗前比较评分有不同程度减少。结论 :养血清脑颗粒治疗紧张性头痛患者效果快且明显 ,对头痛和抑郁症状改善明显 ,对焦虑症状的改善与多塞平相仿 ,但养血清脑颗粒几乎无副作用 ,患者依从性高     

Clevudine University of Georgia/Abbott/Bukwang/Triangle/Yale University

The pyrimidine analog, clevudine (L-FMAU: 2'-fluoro-5-methyl-beta-L-arabinofuranosyluridine) is a potent antihepatitis B virus (HBV) and anti-Epstein-Barr virus (EBV) agent, discovered by researchers at the University of Georgia, in collaboration with Yale University and Bukwang. Bukwang transferred its technology to Triangle Pharmaceuticals in 1998 together with a license to develop clevudine worldwide except Korea [279649], [281942]. In June 1999, Triangle and Abbott Laboratories entered into a strategic alliance to copromote antiviral products including L-FMAU [326798]. In September 2000, Triangle Pharmaceuticals Inc initiated a 30-day phase I/II evaluation of clevudine in HBV-infected patients [381755]. Clevudine is a much less toxic derivative of the toxic agent P-D-FMAU. The mechanism of action of clevudine is not yet clear, but the agent induces a rapid decrease in HBV nucleic acid as doses increase from 0.3 to 10 mg/kg [319145]. It is believed that the target for clevudine lies in the viral replication mechanism. Clevudine is phosphorylated to the triphosphate form intracellularly. This is removed slowly from the cells, thus exerting a sustained inhibitory antiviral activity [178173], [320720], [320721].     

Spotlight from the American Society for Preventive Cardiology on Key Features of the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guidelines on the Management of Blood Cholesterol

The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol retains focus on recommendations for statin treatment in the original four statin-eligible groups [those with atherosclerotic cardiovascular disease (ASCVD), diabetes, low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, and higher risk primary prevention] without the use of treatment initiation or target LDL-C levels from the earlier 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline, but has several new features. First, patients with primary prevention are divided into those who are at low (< 5%), borderline (5% to < 7.5%), intermediate (7.5% to < 20%), and high (≥ 20%) risk based on the ASCVD risk estimator. Moreover, the new guideline goes further to consider a wider range of factors [now called “risk enhancers”—premature family history of ASCVD, persistently high LDL-C, chronic kidney disease (CKD), metabolic syndrome, conditions specific to women, inflammatory diseases, and high-risk ethnicities] that can be used to better inform the treatment decision. Moreover, more detailed recommendations on how the results of coronary calcium scanning can be used to inform the treatment decision are provided, including how it may be used to “de-risk” certain patients for delaying or avoiding the use of statin therapy. There are also specific sections for cholesterol management in other patient subgroups including women, children, certain ethnic groups, those with CKD, chronic inflammatory disorders and HIV, as well as discussion on the management of hypertriglyceridemia. Importantly, for persons with known ASCVD, a distinction is made for those who are at “very high risk” based on having had two major ASCVD events or one major event and two or more other high risk conditions, such as diabetes or other major risk factors, or bypass surgery or percutaneous intervention. Finally, the concept of a threshold LDL-C for initiating a non-statin therapy (after considering highest tolerated statin dosage) is provided, with ezetimibe recommended as the key non-statin to be added if the LDL-C still remains ≥ 70 mg/dL for all ASCVD patients, and in those who are at “very high risk”, further consideration for using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. While the new guideline does have greater detail (and arguably, complexity), the refinements provide a strategy for guiding the clinician to target both statin and non-statin therapy to those most likely to derive benefit.     

Cerebral metabolism of [3H]-p-chloroamphetamine

The time-dependent metabolism of intraventricularly administered $\text{[}{}^3\text{H}\text{]-p-}\text{chloroamphetamine}$ was followed. The parent compound and its metabolites were recovered by high pressure liquid chromatography and characterized by high pressure liquid chromatography, thin-layer chromatography, and gas chromatography-mass spectrometry. By 4 hr after injection, two major toluene-soluble metabolites were present in brain. Their biological half-lives were different from the parent compound. On the basis of their analyses, one of the metabolites is p-chloronorephedrine, the other (P₃) is as yet unidentified. Pretreatment with Lilly 110140 prevented or markedly reduced the synthesis of both p-chloronorephedrine and P₃. Iprindole prevented the synthesis of p-chloronorephedrine. The P₃ appeared first in the brain then in the liver, suggesting that both of these organs can metabolize p-chloroamphetamine to this compound. The metabolites were recovered primarily from the nuclear and microsomal fractions following subcellular fractionation of the brain, with small quantities present in the synaptosomal fraction. The level of metabolites was higher in the brainstem than in the neocortex. Glutathione, administered simultaneously with p-chloroamphetamine either intraventricularly or intraperitoneally failed to alter the toxicity of p-chloroamphetamine.     

Conversion of the N-O-glucuronide and N-O-sulfate conjugates of N-hydroxyphenacetin to reactive intermediates

The N-O-glucuronide of [¹⁴C]acetyl-N-hydroxyphenacetin is sufficiently stable to purify, but slowly breaks down in aqueous solutions to a reactive intermediate that can covalently bind to protein. When the pure compound was incubated in Tris buffer, pH 7.4, at 37°, it decomposed with a half-life of about 8.7 hr to the following compounds: phenacetin, 2-hydroxyphenacetin glucuronide, acetamide and acetaminophen. On addition of glulathione to the systems and allowing the reactions to go to completion, a glutathione-acetaminophen conjugate was formed at the expense of acetamide and acetaminophen: the fraction converted to phenacetin or to the 2-hydroxyphenacetin glucuronide was unchanged. On addition of ascorbic acid to the system and allowing the reactions to go to completion, the fraction converted to acetaminophen was increased at the expense of acetamide: the fractions converted to phenacetin and 2-hydroxyphenacetin glucuronide, however, were again unchanged. When the glucuronide was incubated with bovine serum albumin, covalent binding to the protein occurred at the expense of acetaminophen and acetamide; again, the fraction of the glucuronide converted to phenacetin and 2-hydroxyphenacetin glucuronide was unchanged. Moreover, the covalent binding could be partially prevented by addition of ascorbic acid or glutathione. Since there is formation of covalently bound material, the glutathione conjugate and acetaminophen appear to be interrelated; it seems likely that they are formed from a common intermediate, possibly acetylimidoquinone. However, the data suggest that the formation of phenacetin and 2-hydroxyphenacetin glucuronide occurs by different mechanisms. The N-O-sulfate of [¹⁴C]acetyl-N-hydroxyphenacetin also breaks down to a reactive intermediate that has properties similar to those of the reactive intermediate formed from the N-O-glucuronide and thus may also be N-acetylimidoquinone. By contrast, the relative ability of various nucleophiles to prevent the covalent binding of the reactive intermediate formed from the N-O-sulfate of 2-acetylaminofluorene to protein differs from the relative ability of the nucleophiles to prevent the covalent binding of the reactive intermediate of either the N-O-sulfate or the N-O-glucuronide of phenacetin, suggesting that the relative rates at which these intermediates combine with the different macromolecules may differ markedly.     

甘草配伍大戟的体外肝毒性研究

目的 研究甘草和大戟配伍的体外肝毒性。方法 采用显微观察法和MTT法检测不同浓度的甘草单煎液、大戟单煎液、甘草-大戟合煎液和甘草-大戟单煎混合液对人肝癌细胞HepG2增殖的影响,并比较大戟单煎液、甘草-大戟合煎液和甘草-大戟单煎混合液相当浓度下细胞毒性的大小。结果 大戟单用及大戟与甘草配伍均有细胞毒性,且呈剂量相关性;与大戟单煎液相比,甘草-大戟单煎混合液细胞毒性无明显差异,甘草-大戟合煎液细胞毒性减小。结论 甘草和大戟配伍导致大戟的体外肝毒性减小。     

刺五加的研究进展

刺五加含有苷类、黄酮、多糖等多种活性成分,具有免疫调节、抗肿瘤、抗衰老、抗疲劳等药理作用。对国内外刺五加相关文献进行总结,为刺五加进一步的研究和开发提供参考资料。     

Structure-activity relationships of met5- and leus-enkephalin analogues

1. The effect of various analogues of met5- and leu5-enkephalin were determined on the reduction in twitch height of the electrically-stimulated longitudinal muscle preparation of the guinea-pig ileum and of the isolated mouse vas deferens. 2. In the guinea-pig ileum, D-alanine2-met5-enkephalin was the most potent whereas leu5-enkephalin was the most potent in the mouse vas deferens. 3. The met5-enkephalin analogues were more effective in reducing the twitch height of the ileum than they were in depressing that of the vas deferens preparation. The leu5-enkephalin analogues were more potent in their effects on the mouse vas deferens than they were on the guinea-pig ileum. 4. When a peptide bond is replaced by a glycol bond as in glycol2-3-leu5-enkephalin there is a marked reduction in opiate-like activity. 5. Substitution of a D-alanine residue for the glycine2 residue, as in D-alanine2-met5-enkephalin, increases the duration and potency of opiate-like activity. 6. These results confirm that modification of either met5- or leu5-enkephalin can alter the opiate-like potency of the resulting analogues. It appears that an intact tyrosyl residue of leu5-enkephalin is essential for such activity and that substitution of a D-alanine2 residue for the glycine2 residue confers resistance to enzymatic degradation on the met5-enkephalin peptide. In addition, the glycine2-3 peptide bond is essential for opiate-like activity.     

Quantitative histochemical studies of striatal dopamine depletion following dl-α-methyl-p-tyrosine administration

This study investigated the use of a microfluorimetric histochemical method for the measurement of the depletion of dopamine in the rat caudate nucleus, following α-methyl-p-tyrosine (α-MT) administration. The depletion in three behavioral situations was compared with that of a control group which remained in a cage.The results of the control group indicate that there had been a reduction of approximately 50% in the intensity of the formaldehyde-induced fluorescence derived from dopamine in a region of the neuropil of the caudate nucleus, during the interval (3 hr 40 min) between α-MT, 300 mg/kg i.p., and killing. Disruption of conditioned avoidance response (CAR) performance after α-MT administration was confirmed, but in this study CAR performance in previously trained rats did not have a significant effect on the depletion of formaldehyde-induced fluorescence of the striatal neuropil after α-MT administration. The levels of α-MT-induced depletion of formaldehyde-induced fluorescence in the striatal neuropil following a period of muscular co-ordination/activity and following a period of CAR training were also not significantly different from those shown by a control group.     

Nampt/Visfatin/PBEF研究进展

尼克酰胺磷酸核糖转移酶(nicotinamide phosphoribosyltransferase,Nampt)是生物合成NAD的关键限速酶,又被称为前B细胞克隆增强因子(pre-B cell colony enhancing factor,PBEF)和内脏脂肪素(visfatin).最近研究发现,Nampt/Visfatin/PBEF在NAD生物合成、代谢、炎症反应和细胞增殖、分化、凋亡等诸多领域发挥作用,可能影响2型糖尿病、急性肺损伤、恶性肿瘤等疾病发生、发展和预后.本文主要对Nampt/Visfatin/PBEF的生理功能及临床意义进行综述.