酚氨咖敏片致药物超敏反应综合征

1例43岁女性患者,因感冒口服酚氨咖敏片(1片,tid),第2天停药。用药第5天出现四肢发疹,红斑伴瘙痒明显,用药第7天发展至面部,用药第9天出现高热,实验室检查示白细胞 22.82 × 10_-9?L_-1,中性粒细胞百分率89.3%, 嗜酸性粒细胞百分率2.7%,丙氨酸氨基转移酶95 U?L_-1,门冬氨酸氨基转移酶55 U?L_-1,乳酸脱氢酶228 U?L_-1,磷酸肌酸激酶27 U_?L_-1,总胆红素10.2 μmol?L_-1,直接胆红素3.4 μmol?L_-1,1-3-β-D葡聚糖7.00 pg?ml_-1,内毒素5.00 pg?ml_-1。考虑为酚氨咖敏片致药物超敏反应综合征。给予注射用甲泼尼龙琥珀酸钠(80 mg,qd)、复方甘草酸苷注射液(100 ml,qd)静脉滴注,依巴斯汀片(10 mg,qd)、盐酸赛庚啶片(2 mg,qd)口服。停药第14天面部、躯干、四肢见暗红斑及色素沉着斑片,皮疹明显消退,白细胞14.95 × 10_-9?L_-1,中性粒细胞百分率72.0%, 嗜酸性粒细胞百分率1.2%,丙氨酸氨基转移酶44 U?L_-1,门冬氨酸氨基转移酶14 U?L_-1,乳酸脱氢酶165 U?L_-1,磷酸肌酸激酶14 U?L_-1,总胆红素9.0 μmol?L_-1,直接胆红素1.9 μmol?L_-1。停药后6周,皮疹全部消退,皮肤颜色基本正常。     

马来酸依那普利片稳定性研究

目的 提高马来酸依那普利片的稳定性。方法 将马来酸依那普利原料和碳酸氢钠以1:3的摩尔比溶解在水中,作为粘合剂使用。结果 通过原辅料相容性试验表明,处理后的API与各辅料相容性较好,杂质没有明显变化;通过制剂的加速6个月试验表明：杂质C由0.15%增长至0.61%,杂质D由未检出增长到0.48%;通过长期12个月的数据表明：杂质C由0.15%增长至0.42%,杂质D由未检出增长至0.1%。结论 通过原辅料相容性和稳定性考察结果显示,该工艺有效解决了马来酸依那普利制剂稳定性不好的问题。     

甲钴胺与马来酸桂哌齐特联合治疗糖尿病下肢神经病变的疗效观察

目的：探讨甲钴胺与马来酸桂哌齐特在2型糖尿病合并下肢周围神经病变治疗中的疗效及血管内皮功能的变化.方法：选择2型糖尿病合并下肢周围神经病变的病例60例,随机分甲钴胺治疗组（1组）和甲钴胺与马来酸桂哌齐特治疗组（2组）,每组30例,1组给予甲钴胺治疗,2组在甲钴胺治疗的基础上加用马来酸桂哌齐特治疗,疗程14天,治疗前后观察临床症状,测定血管内皮细胞功能和肌电图.结果：经过治疗,1组运动传导速度、感觉传导速度,以及临床症状有一定程度的改善,但差异无显著性意义（P＞0.05）,2组治疗后运动传导速度、感觉传导速度明显增快,同时临床症状改善明显（P＜0.01）;两组治疗前血内皮素、D-二聚体和C反应蛋白（CRP）均高于正常,治疗前后比较差异有显著性意义（P＜0.05）,而1组血内皮素、D-二聚体和CRP均有一定程度的下降但差异无显著性意义（P＞0.05）.结论：甲钴胺与马来酸桂哌齐特联合治疗在2型糖尿病合并下肢周围神经病变治疗中可改善血管内皮的功能和下肢周围神经病变,缓解临床症状,疗效显著.     

高效液相色谱法测定马来酸阿塞那平的有关物质

目的：建立反相高效液相色谱法定量测定马来酸阿塞那平中的8个杂质。方法：色谱柱采用Inertsil ODS-3 C18（250 mm ×4.6 mm,5μm）,流动相A为0.1%三氟乙酸水溶液,流动相B为乙腈,以1.0 ml·min^-1的流速进行梯度洗脱,检测波长为220 nm,柱温为35℃。结果：阿塞那平与各杂质峰良好分离,阿塞那平在0.45~1458μg·ml^-1浓度范围内线性关系良好（r=1.0000）,各杂质在0.4~30.0μg·ml-^1浓度范围内线性关系良好（r〉0.999）;平均回收率93.1%~106.7%（n=9）。结论：本方法操作简便、灵敏度高、重复性好、专属性和耐用性较强,可用于测定马来酸阿塞那平原料药的有关物质。     

HPLC法测定复方愈酚麻黄糖浆中四种成分的含量

目的建立测定复方愈酚麻黄糖浆中盐酸麻黄碱、愈创甘油醚、马来酸氯苯那敏、双氯芬酸含量的HPLC方法。方法采用Insteril ODS-3C18色谱柱,梯度洗脱,流速：1．0mL·min^-1,柱温：30℃,检测波长：257nm。结果盐酸麻黄碱、愈创甘油醚、马来酸氯苯那敏、双氯芬酸分别在0．4018～6．4287μg（r=0．9999）、3．1836～50．9379μg（r=0．9999）、0．1610～2．5762μg（r=1．0000）、0．1485～2．3759μg（r=0．9999）范围内线性关系良好,平均回收率分别为99．589／6（RSD=0．39％）、99．58％（RSD=0．30％）、99．36％（RSD=0．29％）、99．40％（RSD=0．46％）（n=9）。结论本方法经方法学验证可用于复方愈酚麻黄糖浆中盐酸麻黄碱、愈创甘油醚、马来酸氯苯那敏、双氯芬酸的含量检测。     

黛力新联合马来酸曲美布汀治疗腹泻型肠易激综合征的疗效观察

目的：观察黛力新联合马来酸曲美布汀治疗腹泻型肠易激综合征的疗效。方法将2012年8月~2013年8月来本院治疗腹泻型肠易激综合征的38例患者随机分为观察组和对照组,每组19例。两组患者均给予马来酸曲美布汀治疗,观察组加用黛力新,治疗6周。比较两组患者的治疗有效率,记录患者治疗前后的SDS评分和SAS评分,并进行比较。结果观察组总有效率94.74%高于对照组68.42%,两者差异有统计学意义（P〈0.05）;观察组治疗后SDS评分以及SAS评分均低于对照组,两者差异有统计学意义（P〈0.05）。结论黛力新联合马来酸曲美布汀治疗腹泻型肠易激综合征的疗效可靠,值得临床推广应用。     

马来酸桂哌齐特治疗急性脑梗死的疗效及对血液流变学的影响

目的：观察马来酸桂哌齐特注射液治疗急性脑梗死的临床效果及对血液流变学的影响。方法选择2009-12-2012-12我院内科收治的急性脑梗死患者133例,随机分为治疗组68例和对照组65例。2组均给予常规基础治疗,治疗组在对照组基础上应用马来酸桂哌齐特注射液320 mg加入500 mL 0.9％氯化钠注射液中静滴,1次/d ,共应用14 d ,治疗前后采用改良爱丁堡-斯堪的那维亚量表（SSS ）与日常生活能力（ADL ）量表对2组患者的疗效进行评定。对比治疗前后2组患者血液流变学指标变化。结果治疗7 d、14 d后治疗组SSS评分、ADL评分与对照组比较差异有统计学意义（ P＜0.05）。治疗组治疗前后SSS评分、ADL评分比较差异有统计学意义（ P＜0.05）。2组治疗后总有效率比较差异有统计学意义（ P＜0.05）。治疗组治疗后血液流变学指标均较治疗前有显著改善（ P＜0.05）。结论马来酸桂哌齐特注射液治疗急性脑梗死安全有效,且能显著改善患者的血液流变学指标。     

Functional characterization of histamine H4 receptor on human mast cells

Among the four different types of histamine receptors (H1-H4), H4R is predominantly expressed in immune cells and involved in immunomodulatory response. Here, in this study we determined the expression of H4R in human mast cells (HMC-1, LAD-2 and primary cord blood derived CD34+ human mast cells) and characterized its functional properties. Interestingly, we found that human mast cells responded to both histamine (natural ligand) and 4-methylhistamine (selective H4R agonist) for sustained intracellular calcium mobilization, degranulation and cytokine production. However, only histamine induced the release of cAMP, but 4-methylhistamine down regulates cAMP indicating that H4R mediates its effect through Gαi/o protein and H1R via Gαq protein. Furthermore, both histamine and 4-methylhistamine induced the production of cysteinyl leukotrienes and LTB4. Using human inflammation antibody array membrane, we found that H4R induced the expression of various inflammatory proteins, involving pro-inflammatory cytokines and chemokines and these are TGF-β1, TNF-α, TNF-β, PDGF-BB, TIMP-2, M-CSF, IP-10, IL-16, IL-6, IL-3, IL-10, MIP-1α, IL-1α, ICAM-1, Eotaxin-2, RANTES, IL-8, MCP-1, and IL-6sR. We also quantified the level of various inflammatory cytokines produced by human mast cells through H4R. It was observed that, the production level of Th2 cytokines IL-4(401.34 pg/ml), IL-5 (64.21 pg/ml) and IL-13 (1044 pg/ml) and classical proinflammatory cytokines IL-6 (221.27 pg/ml) and IL-1β (34.24 pg/ml) and chemokines MCP-1(106 pg/ml) and IL-8 (818.32 pg/ml). Furthermore, activation of H4R caused the phosphorylation of ERK and PI3 K in a time dependent manner. Taken together these data demonstrate that, the activation of H4R in human mast cells produced not only inflammatory mediators that are associated with allergic reactions but also other inflammatory conditions.     

欣母沛、缩宫素联合马来酸麦角新碱预防二次剖宫产术后出血的效果

目的探讨欣母沛、缩宫素联合马来酸麦角新碱预防二次剖宫产术后出血的效果。方法将72例二次剖宫产产妇按照随机数表法分为观察组(欣母沛、缩宫素联合马来酸麦角新碱治疗)与对照组(缩宫素治疗),各36例。比较两组的预防效果。结果观察组的术后2、24 h出血量、产后出血发生率及子宫复旧情况均优于对照组(P<0.05)。治疗后24 h,两组的Hb、HCT、Ca2+、FIB、D-D水平均有所改善,且观察组优于对照组(P<0.05)。结论欣母沛、缩宫素联合马来酸麦角新碱可有效预防二次剖宫产术后出血,且不增加不良反应。     

马来酸桂哌齐特治疗高血压性脑出血临床疗效及安全性观察

目的 探讨马来酸桂哌齐特对高血压性脑出血的出血、水肿吸收以及神经功能损伤恢复方面的临床疗效,同时观察其不良反应.方法 98例高血压性脑出血患者,随机分为对照组和治疗组,对照组给予高血压性脑出血常规治疗,治疗组加用马来酸桂哌齐特320mg静滴,每日1次,共用14d.分别于治疗前、治疗14d后测定血肿和水肿体积、NIHSS评分、Barthel指数及血压、心率水平、血白细胞计数(WBC)、肝肾功能、血糖及凝血功能,并观察不良反应发生情况.结果 治疗14d后治疗组血肿、水肿体积均较对照组明显缩小,差异具有统计学意义(P<0.05);两组病例NIHSS评分及BI评分治疗前后差异均有统计学意义(P<0.05),治疗14d后治疗组NIHSS评分及BI评分差异具有统计学意义(P<0.05);两组显效率及总有效率差异均具有统计学意义(P<0.05);治疗组治疗前后患者心率、血白细胞计数(WBC)、肝肾功能及凝血功能等各项指标差异均无统计学意义.结论 马来酸桂哌齐特可促进高血压性脑出血水肿和血肿吸收,改善神经功能缺损及病残程度,不良反应出现少,安全性较好.

Abstract：

Objective To evaluate the clinical efficacy and safety profile of cinepazide maleate for the treatment of hypertensive hemorrhage by observing the absorption of blood blots and brain edema, recovery of nervous system functions,and adverse reaction of this drug. Methods 98 patients with hypertensive hemorrhage were divided into two groups randomly:the control group and the therapy group. Patients in the control group were given routine treatment, while patients in therapy group were administrated with cinepazide maleate 320mg ivgtt. Qd, and the course of treatment was 14 days for both groups. Volume of blood blot and edema, NIHSS score, Barthel index (BI), blood pressure, heart rate, WBC, ALT, AST, Cr,BUN, blood glucose and blood clotting function of each patient were all evaluated before and after treatment course;meanwhile, adverse reactions were under tight observations. Results After treatments for 14 days,a significant decrease in volumes of blood blot and edema was noticed in all patients of therapy group compared to those of control group ( P < 0.05 ).Statistical differences of NIHSS score and BI were observed in two groups before and after treatments ( P < 0.05 ), this trend also existed in the comparison between therapy group and control group ( P < 0. 05 ). There were significant differences of effect efficiency in two groups ( P < 0. 05 ), with the same as the total effect efficiency ( P < 0.05 ). No statistical differences of heart rate,WBC,ALT, AST, Cr, BUN, blood glucose and blood clotting function were detected in therapy group before and after treatments. Conclusions Cinepazide maleate may facilitate the absorption of blood blot and edema for patients with hypertensive hemorrhage, improve the impaired function of nervous system, and decrease the disability extent.Moreover,cinepazide maleate is a safe drug with few adverse reactions.