盐酸小檗碱片联合四联疗法根治幽门螺杆菌的疗效观察

目的:对比盐酸小檗碱片联合四联疗法和四联疗法根除幽门螺杆菌(Hp)方案的临床效果,为临床治疗方案的选择提供参考。方法:将160例幽门螺杆菌阳性消化性溃疡患者随机分为两组。A组:口服埃索美拉唑(20 mg)+阿莫西林(1.0 g)+枸橼酸铋钾(220 mg)+克拉霉素(0.5 g),每日2次,服用10 d。B组:口服埃索美拉唑(20 mg)+枸橼酸铋钾(220mg)+阿莫西林(1.0g)+克拉霉素(0.5g),每日2次,盐酸小檗碱片300 mg,每日3次,服用10 d。观察记录Hp根除情况及不良反应。结果:两组Hp根除率分别为81.23%和87.50%,差异有统计学意义(P<0.05)。两组不良反应率比较,差异无统计学意义(P<0.05)。结论:盐酸小檗碱片联合铋剂四联组不良反应未明显增加,根除率更高,是较理想的治疗方案。     

细辛木脂素抗心脏移植急性排斥反应的实验观察

目的:观察细辛木脂素(Herba Asari Ligini,HAL)对大鼠同种异位心脏移植急性排斥反应的治疗效果,为抗排斥药物的研究提供实验依据。方法:建立大鼠同种异位心脏移植模型,受体自术前1天至术后14天分别给予 CsA10mg/kg/d、CsA2.5mg/kg/d、HAL50mg/kg/d、HAL50MG/kg/d+CsA2.5mg/kg/d 观察移植心存活时间。结果:单用 HAL 组的移植心存活时间比对照组长(P<0.01),但短于 CsA10mg/kg/d 组(P<0.01);CsA2.5mg/kg/d 组与 HAL50mg/kg/d合用组的移植心存活时间与 CsA10mg/kg/d 组相拟(P>0.05)。结论:HAL 具有抗排斥作用,但效果低于治疗量(10mg/kg/d)的 CsA;HAL 与 CsA 抗急性排斥反应具有协同作用。     

盐酸小檗碱联合辛伐他汀对实验性高脂血症的降血脂作用研究

目的观察盐酸小檗碱联合辛伐他汀对实验性高脂血症大鼠的降血脂作用。方法以高脂饲料喂养建立大鼠高脂血症模型,将大鼠分为正常对照组、模型组(生理盐水)、辛伐他汀组12 mg/(kg·d)、盐酸小檗碱联合辛伐他汀低、中、高三个剂量组[60+6 mg/(kg·d)、90+6 mg/(kg·d)和120+6 mg/(kg·d)],每组10只,连续灌胃给药21 d后取血清对高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)和总胆固醇(TC)水平进行测定。结果辛伐他汀治疗组的TC和LDL-C较之模型组明显降低,差异具有统计学意义(P<0.05),联合治疗各剂量组大鼠的LDL-C、TG和TC水平均明显降低,差异也具有统计学意义(P<0.05),且效应呈现一定的剂量相关性;另外,联合治疗高剂量组大鼠的HDL-C水平明显升高,差异也具有统计学意义(P<0.05)。结论盐酸小檗碱联合辛伐他汀可有效改善实验性高脂血症大鼠的脂质水平,且可减少他汀类药物的用量,盐酸小檗碱可作为降血脂药物的理想补充,为患者提供新的治疗选择。     

盐酸小檗碱炉甘石洗剂的制备及临床应用

目的 :介绍盐酸小檗碱炉甘石洗剂的制备 ,质量检验及其治疗小儿痱子的疗效。方法 :按照混悬剂配制方法制备盐酸小檗碱炉甘石洗剂和建立质量标准 ,并设立炉甘石洗剂作为对照组观察疗效。治疗组 (盐酸小檗碱炉甘石洗剂 ) 143例 ;对照组 (炉甘石洗剂 ) 139例 ,观察两组的疗效。结果 :治疗组有效率为 99% ,平均治愈时间 ( 3 2± 1 2 )d ;对照组有效率 96% ,平均治愈时间 ( 4 2± 1 3)d。结论 :经统计学检验 ,两组差异显著 ,本洗剂优于炉甘石洗剂     

盐酸小檗碱对丙酸睾酮诱导的前列腺增生小鼠的作用及其机制研究

目的研究盐酸小檗碱对丙酸睾酮诱导的前列腺增生小鼠的作用及其机制。方法使用丙酸睾酮诱导建立前列腺增生小鼠模型,造模成功后,选择雄性昆明小鼠40只,随机分为4组,分别为模型组(生理盐水组)、盐酸小檗碱低剂量(10 mg/ml)组、盐酸小檗碱中剂量(20 mg/ml)组、盐酸小檗碱高剂量(40 mg/ml)组,每组10只,连续给药10 d后,记录各组小鼠每日尿量及10 d累计尿量,计算给药前后各组小鼠体重减轻值,检测各组小鼠血浆中TNF-α、IL-6、IL-10及IL-1β水平,取小鼠前列腺组织并计算脏器指数,苏木精-伊红染色法观察各组小鼠前列腺组织病理切片,Western blot法检测各组小鼠前列腺组织中VEGF、AKT、caspase-12蛋白表达情况。结果与模型组相比,盐酸小檗碱各剂量组小鼠累计尿量呈剂量依赖性显著增加(P<0.05),且随着给药时间的延长,盐酸小檗碱各剂量组小鼠每日尿量逐渐增加;与模型组相比,连续给药10 d后,盐酸小檗碱各剂量组小鼠的体重减轻值呈剂量依赖性显著增加(P<0.05),盐酸小檗碱各剂量组小鼠体内TNF-α、IL-6、IL-10及IL-1β等炎症因子水平、前列腺脏器指数均呈剂量依赖性显著降低(P<0.05)。病理组织学检查结果显示,与模型组相比,盐酸小檗碱各剂量组细胞形态明显改善,细胞排列整齐,腺体乳头向腔内扩张明显缩小,盐酸小檗碱中、高剂量组前列腺组织细胞形态圆润,结节样增生少见,盐酸小檗碱高剂量组小鼠的前列腺组织腺体乳头无异常突出;Western blot结果表明,与模型组相比,盐酸小檗碱各剂量组小鼠前列腺组织中VEGF及AKT表达量均呈剂量依赖性显著降低(P<0.05),caspase-12表达量呈剂量依赖性显著增加(P<0.05)。结论盐酸小檗碱能够抑制丙酸睾酮诱导的前列腺增生小鼠前列腺组织的增生,其作用机制可能与调节前列腺组织VEGF、AKT及caspase-12等蛋白的表达有关。     

酪酸梭菌活菌散联合锌剂治疗婴幼儿肺炎继发性腹泻的疗效观察

目的:观察酪酸梭菌活菌散联合锌剂治疗婴幼儿肺炎继发性腹泻的疗效。方法:婴幼儿肺炎继发性腹泻患儿240例,随机分为治疗组和对照组各120例。两组在积极治疗原发病基础上给予纠正脱水、电解质紊乱及酸碱平衡等对症支持治疗;对照组给予酪酸梭菌活菌散口服,1岁以内每次0.25 g,1岁以上每次0.5 g,3次/天,疗程7～10 d;治疗组口服酪酸梭菌活菌散联合葡萄糖酸锌,以锌计算,1岁以内10 mg/d,1岁以上20 mg/d,疗程均7～10 d。比较两组脱水纠正时间、恢复进食时间、住院时间及治疗后的有效率。结果:治疗组总有效率96.7%,对照组总有效率75.8%,两组比较差异有统计学意义(P<0.01)。治疗组平均住院时间为(5.6±1.8)d,对照组平均住院时间为(8.7±2.2)d,两组比较差异有统计学意义(P<0.01)。结论:酪酸梭菌活菌散联合锌剂治疗婴幼儿肺炎继发性腹泻安全有效,能缩短治疗时间,值得临床推广。     

盐酸小檗碱对大鼠肝微粒体细胞色素P450酶含量及活性的影响

目的考察盐酸小檗碱对大鼠肝微粒体的蛋白含量、CYP450酶总量和主要CYP450酶亚型(CYP1A2、CYP2D6、CYP3A4和CYP2C19)活性的影响。方法以溶剂为空白对照灌胃给予盐酸小檗碱250 mg/(kg·d),连续7 d,测定其肝微粒体蛋白含量、CYP450蛋白含量以及CYP1A2、CYP2D6、CYP3A4和CYP2C19活性。结果与空白对照组比较,盐酸小檗碱给药组大鼠肝微粒体蛋白含量及肝微粒体CYP450含量无明显差异(P>0.05)。盐酸小檗碱给药后,给药组大鼠的平均CYP3A4活性是空白对照组的1/2;而两组之间CYP1A2、CYP2D6和CYP2C19的活性相当。结论盐酸小檗碱对大鼠CYP3A4活性有一定抑制作用,对CYP1A2、CYP2D6和CYP2C19的活性没有影响。     

黄芩苷与盐酸小檗碱自沉淀理化性质及抑菌作用机制研究

目的 以黄芩苷和盐酸小檗碱产生的自沉淀为研究对象,探究其理化性质,对其抑菌作用及其机制展开研究,为中药自沉淀现象产生的物质深入研究提供参考。方法 采用差示热量扫描法、红外光谱扫描和紫外光谱扫描测定黄芩苷和盐酸小檗碱的自沉淀理化性质;采用牛津杯法探索黄芩苷、盐酸小檗碱及自沉淀对大肠埃希菌、金黄色葡萄球菌的抑菌活性;采用二倍稀释法进一步研究黄芩苷、盐酸小檗碱、自沉淀对大肠埃希菌和金黄色葡萄球菌的最小抑菌浓度(MIC)和最小杀菌浓度(MBC),并通过测定菌体的生长曲线、胞外核酸相对含量、胞外可溶性蛋白质含量和电导率研究黄芩苷、盐酸小檗碱及自沉淀对大肠埃希菌、金黄色葡萄球菌的抗菌机制,分析对比黄芩苷、盐酸小檗碱反应前后抑菌作用机制是否发生改变。结果 差示热量扫描法结果显示盐酸小檗碱与黄芩苷反应前后存在热量变化,该自沉淀是一种不同于盐酸小檗碱、黄芩苷的新物质或复合物,其官能团、紫外吸收均发生了变化。盐酸小檗碱对大肠埃希菌的MIC为0.9375 mg/mL,MBC为7.5 mg/mL;对金黄色葡萄球菌的MIC为0.9375 mg/mL,MBC为7.5 mg/mL。黄芩苷对大肠埃希菌的MIC为1.8...     

盐酸小檗碱对小鼠移植性肿瘤的抑制作用

目的 研究盐酸小檗碱的体内抗肿瘤活性.方法 应用移植性实体瘤H22,宫颈癌U14,肉瘤S180荷瘤小鼠作为动物模型,腹腔给药观察小鼠生长情况,并计算抑瘤率.结果 盐酸小檗碱10,20,25 mg/kg剂量对肝癌H22的抑制率分别为25.82%,36.81%和40.66%;盐酸小檗碱10,20 mg/kg剂量对宫颈癌U14抑制率分别为37.80%和59.90%;盐酸小檗碱15,20 mg/kg剂量对肉瘤S180的抑制率分别为30.85%和39.80%.结论 盐酸小檗碱可抑制肝癌H22、宫颈癌U14、肉瘤S180在小鼠体内的生长.     

氟康唑联合乳杆菌活菌制剂用于外阴阴道假丝酵母菌病疗效分析

目的:探讨氟康唑联合乳杆菌活菌制剂治疗外阴阴道假丝酵母菌病的效果.方法:将92例外阴阴道假丝酵母菌病的妇女随机分为观察组和对照组,每组各46例.观察组采用乳杆菌活菌胶囊(定君生)与氟康唑联合用药:口服氟康唑150 mg,连用3 d;阴道冲洗后于阴道后穹窿放置乳杆菌活菌制剂1枚,连用10 d.对照组仅口服氟康唑150 m...     

大蒜素联合氟康唑对假丝酵母体外抗菌活性的影响

目的 研究大蒜素与氟康唑体外联合应用对临床分离假丝酵母联合抗菌效应的影响。方法 采用棋盘法设计，微量稀释法测定不同浓度组合的大蒜素及大蒜素和氟康唑联合应用分别对65 株假丝酵母的最低抑菌浓度，并计算FIC 指数，判定联合抗菌效应；用10% 的小牛血清-RPMI1640 培养基诱导菌丝形成，检测大蒜素与氟康唑联合应用对假丝酵母芽管率和菌丝形成的影响。结果 大蒜素与氟康唑联合对假丝酵母的敏感菌株和耐药菌株的MIC50 均降低，较单用氟康唑和大蒜素分别降低8 倍和5 倍( 分别为由64μg/mL 降至0.25μg/mL、由32μg/mL 降至2μg/mL)；FIC 指数分布：FIC ≤ 0.5 占100%，表现为协同作用；大蒜素能加强氟康唑抑制菌丝的形成。结论 大蒜素与氟康唑联用后，对假丝酵母表现为协同抗菌作用，能显著提高氟康唑对假丝酵母的杀菌活性。     

Synergic anticandidal effect of epigallocatechin-O-gallate combined with amphotericin B in a murine model of disseminated candidiasis and its anticandidal mechanism

In the present study, we investigated synergic anticandidal effect of epigallocatechin-O-gallate (EGCG) in a murine model of disseminated candidiasis caused by Candida albicans. In addition, its mechanism was examined. In the animal system, EGCG-given BALB/c mice group intraperitoneally (i.p.) before intravenous (i.v.) inoculation with viable C. albicans yeast cells survived longer than diluent-received (control) mice group (p<0.05). EGCG treatment inhibited the hyphal formation from the yeast form of C. albicans, causing growth-inhibition of the candidal cells. In experiments determining synergic effect, mice given diluent (control), Amp B (amphotericin B; 0.5 mg/kg of body weight), or EGCG (2 mg/kg) had mean survival times (MST) of approximately 10.9, 11.7, and 13.9 d, respectively. However, mice administered combination of Amp B (0.5 mg/kg) plus EGCG (2 mg/kg) had a MST value of 42.1 d, surviving an average of app. 30 d longer than the Amp B alone-received mice groups. The MST value from the combination-treated mice groups was much greater than MST value from mice groups that received four times the Amp B dose. These results indicate that EGCG, which has anticandidal activity causing blockage of the hyphal formation, has the synergism combined with Amp B against disseminated candidiasis.     

氟康唑协同土槿皮甲酸抗白念珠菌活性研究

摘要：目的 研究体外土槿皮甲酸(PAA)与氟康唑(FLC)联合应用对白念珠菌的抗菌活性。方法 采用微量稀释法和棋盘 微量稀释法测定PAA与FLC单独应用及联合应用于对临床分离的22株白念珠菌的最低抑菌浓度(MIC),并以部分抑菌浓度指数 (FICI)判断两药联合抑菌效应,以CAR3和CA10为目标菌株,采用时间-杀菌曲线动态监测两药体外抑菌效果。结果 PAA单独 作用于白念珠菌时,无论是对FLC耐药菌株还是对FLC敏感菌株,均呈现较好的抑菌效果,其中位MIC范围为4~16μg/mL。当 PAA与FLC联用对抗耐药白念珠菌时,可将FLC的单用浓度范围从256~512μg/mL降至为1~2μg/mL。根据FICI测定,11株对FLC 耐药菌株FICI介于0.039~0.253之间,均表现出协同抑菌作用;而11株对FLC敏感菌株,仅有2株(18.2%)FICI范围为0.312~0.375, 呈现出协同抑菌作用,剩余9株(81.8%)FICI介于0.625~1.125之间,两种药物呈现出无关作用。时间-杀菌曲线也证实,与氟康唑 单用相比,PAA与FLC联用24h后,CAR3、CA10菌株的lgCFU/mL分别下降了2.22个单位和1.57个单位,耐药菌株表现出协同作 用,而敏感菌株表现出无关作用。结论 PAA对白念珠菌表现出较好的抑菌效力,与低浓度FLC联用对耐药白念珠菌具有体外 协同抑菌作用,能显著提高FLC对耐药白念珠菌的抗菌活性。     

抗菌药物联合中药单体对泛耐药鲍曼不动杆菌生物被膜的影响

摘要：目的 研究4种抗菌药物(亚胺培南、美罗培南、多黏菌素B和替加环素) 和3种中药单体(黄芩苷、盐酸小檗碱和槲皮素二水物)对泛耐药鲍曼不动杆菌(XDRAB)生物被膜形成能力的影响,并探讨以上组合用药对XDRAB的协同抗生物被膜效应。方法 收集2018-2019年成都医学院第一附属医院的不同科室的临床标本分离的9株XDRAB,采用比浊法测定4种抗菌药物、3种中药单体在1 MIC、1/2 MIC、1/4 MIC、1/8 MIC、1/16 MIC对9株XDRAB 24 h内的生长情况;结晶紫棋盘染色法检测工作浓度下亚胺培南、美罗培南、替加环素、多黏菌素B、黄芩苷、盐酸小檗碱和槲皮素二水物单用对生物被膜的抑制作用和组合联用的协同抗生物被膜效应。结果 亚胺培南(4 μg/mL)、美罗培南(2 μg/mL)、多黏菌素B(0.25 μg/mL)、替加环素(0.0625 μg/mL)、黄芩苷(128 μg/mL)、盐酸小檗碱(32 μg/mL)、槲皮素二水物(64 μg/mL)的浓度时24 h内不抑制细菌的生长,以此浓度为基础倍比稀释,设置高、中、低三个浓度梯度;与模型对照组相比,4种抗菌药物、3种中药单体、在高浓度下单用、联用均可以明显抑制XDRAB生物被膜的形成(P＜0.05),联合用药效果均优于单独用药(P＜0.05),表现为不同程度的协同抗生物被膜作用,其中替加环素与黄芩苷的9个浓度组合均能够显著抑制XDRAB生物被膜的形成,0.015625 μg/mL替加环素与32 μg/mL黄芩苷与的浓度组合下,药物剂量最小。结论 4种抗菌药物亚胺培南、美罗培南、多黏菌素B、替加环素,3种中药单体黄芩苷、槲皮素二水物、盐酸小檗碱单用及联用时对XDRAB的生物被膜形成均具有不同程度的抑制作用,联合用药均表现为不同程度的协同抗生物被膜效应。     

New heterocyclic derivatives of benzimidazole with germicidal activity. IV--In vivo anticandida activity of 5-fluoro-2-(5'-nitro-2'-furyl) benzimidazole (F-O-NO2)

We have studied the possible in vitro and in vivo antibacterial activity of 5-fluoro-2-(5'-nitro-2'-furyl)benzimidazole (F-O-NO2). Our data demonstrate that F-O-NO2 is able to inhibit the in vitro growth of different mycetes and bacteria, including Candida albicans and Cryptococcus neoformans. We also tested the possible in vivo activity against Candida albicans. The results clearly show that treatment with F-O-NO2 is able to significantly augment the survival of all treated animals; in particular, when injected i.p. at the dose of 120 mg/kg, 30' or 1 hr after Candida albicans challenge, it givens a MST (Medium Survival Time) longer than 60 days. These data demonstrate that F-O-NO2 has antibacterial and antimycotic activity.     

Berberine synergy with amphotericin B against disseminated candidiasis in mice

In present study, we investigated the synergic effect of berberine against disseminated candidiasis caused by the pathogenic fungus, Candida albicans. Berberine inhibited the growth of C. albicans under in-vitro condition. The broth susceptibility revealed the synergic effect of berberine with amphotericin B (Amp B). To confirm these results under the in-vivo condition, the effect was examined in mice against disseminated candidiasis. Results showed mice that were given diluent (negative control), Amp B (0.5 mg/kg of body weight), or berberine (1 mg/kg of body weight) had mean survival times (MST) of approximately 12, 14, and 17 d, respectively. On the contrary, mice that were treated using a combination of the two agents at the same concentrations resulted in a MST value of 36 d, surviving at an average of 22 d longer than the mice group treated only with the Amp B. This MST value was almost same as MST value from the mice that were given four times the Amp B dose. These data indicate that the combination of Amp B and berberine could reduce approximately 75% of the Amp B dose, implying that berberine indeed has synergy with Amp B against the disseminated disease.     

Prophylactic efficacy of a basidiomycetes preparation AHCC against lethal opportunistic infections in mice

The prophylactic effects of a Basidiomycetes preparation, AHCC, against experimental opportunistic infections were investigated in leukopenic mice. In cyclophosphamide-induced leukopenic mice, oral or intraperitoneal administration of the AHCC at doses of 1000 or 50 mg/kg/day, respectively, for 4 consecutive days prior to Candida albicans infection significantly prolonged the survival periods of the infected mice, and decreased the viable counts of C. albicans cells recovered from their kidneys. Similarly, the oral treatment with AHCC protected mice from lethal infection with Pseudomonas aeruginosa and intraperitoneal one also protected mice from infection with methicillin-resistant Staphylococcus aureus (MRSA). These results suggest a potential usefulness of the AHCC as a prophylactic agent for the management of patients with opportunistic infections.     

Immunosuppression and recovery of drug-impaired host resistance against Candida albicans infection by oxoglaucine.

The immunosuppressive action of aporphinoid alkaloid oxoglaucine was studied in experimental Candida albicans (C. albicans) infection in mice. The alkaloid augmented host resistance to pathogen applied to mice (6-8 weeks of age) at a low dose of 2 mg kg(-1) in 3 days and impaired it at a high dose of 10 mg kg(-1). The suppressive activity observed under the latter schedule correlated with the inhibited proliferative response of splenic cells to mitogens and with decreased popliteal lymph node (PLN) reaction to C. albicans. Treatment of mice with oxoglaucine (at the age of 5 days) at a dose of 5 mg kg(-1) in 3 consecutive days increased the susceptibility to Candida inoculation at the age of 6 weeks. Delayed type hypersensitivity (DTH) response to C. albicans was enhanced after pretreatment of adult mice and was suppressed after administration to newborn mice. Long-time treatment (10 days) with oxoglaucine, cyclophoshamide or prednisolone at a dose of 10 mg kg(-1) increased the rate of mortality of Candida-infected mice. Combined pretreatment of mice with cyclophosphamide or prednisolone (5 days at a dose of 5 mg kg(-1)) followed by oxoglaucine (5 days at a dose of 5 mg kg(-1)), prolonged the survival of infected mice.     

Interaction of inducible nitric oxide synthase and cyclooxygenase-2 inhibitors in formalin-induced nociception in mice

Studies with inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 inhibitor were conducted to assess their synergistic antinociceptive effect and possible therapeutic advantage. The antinociceptive interaction of rofecoxib, a selective cyclooxygenase-2 inhibitor, with aminoguanidine hydrochloride, a selective iNOS inhibitor, was examined in the formalin-induced paw-licking model in mice. Analysis of variance (ANOVA) and the isobolographic method were used to identify the nature of the antinociceptive interaction. Different doses of rofecoxib (1, 3, 10 and 30 mg/kg) and aminoguanidine hydrochloride (10, 30, 100 and 300 mg/kg) alone were administered orally to adult male albino mice (20-30 g). Only high doses of rofecoxib (10 and 30 mg/kg) and aminoguanidine hydrochloride (100 and 300 mg/kg) showed a statistically significant antinociceptive effect. Combination of a subthreshold dose of rofecoxib (1 mg/kg) with increasing doses of aminoguanidine hydrochloride (30, 100 and 300 mg/kg) resulted in potentiated antinociception (P<0.05). Combined therapy with a subthreshold dose of aminoguanidine hydrochloride (30 mg/kg) with increasing doses of rofecoxib (1, 3, 10 and 30 mg/kg) also resulted in significant antinociception (P<0.05). These results suggest that rofecoxib and aminoguanidine hydrochloride act synergistically in their antinociceptive action in mice. A possible mechanism of interaction is that nitric oxide (NO) stimulates the activity of cyclooxygenase-2 by combining with its heme component. Furthermore, the present results suggest that combination therapy with rofecoxib and aminoguanidine hydrochloride may provide an alternative for the clinical control of pain.