克霉唑联合咪康唑治疗妊娠期念珠菌性阴道炎的疗效观察

目的:观察克霉唑联合咪康唑治疗妊娠期念珠菌性阴道炎的临床疗效及安全性。方法:将我院2008年1月-2010年2月收治的100例妊娠期念珠菌性阴道炎患者,随机1:1分为观察组和对照组。对照组用碱性洗液冲洗外阴后,将克霉唑阴道片500mg置入阴道深部;观察组在对照组基础上给予咪康唑霜涂擦瘙痒处,每天2～3次。2组均7d为1个疗程。治疗后第1、4周复查疗效,比较2组患者的治疗有效率、复发率和症状改善率。结果:观察组总有效率为96.0%,复发率为6.0%;对照组总有效率为82.0%,复发率为24.0%。2组总有效率、复发率比较,差异均具有统计学意义(P<0.05)。观察组症状改善率分别为96.0%、88.4%、95.0%;对照组症状改善率分别为82.0%、68.2%、75.6%,2组比较差异有统计学意义(P<0.05)。随访至分娩,均未发生孕产妇感染、早产、新生儿畸形。结论:克霉唑联合咪康唑治疗妊娠期念珠菌性阴道炎安全有效,复发率低。     

Improvement of solubility and dissolution properties of clotrimazole by solid dispersions and inclusion complexes

Solid dispersions of a slightly water-soluble drug, clotrimazole, were prepared in different weight ratios using polyethyleneglycol 4000 and different molecular weight polyvinyl pyrrolidones as carriers. Moreover, binary and ternary β-cyclodextrin complexes were prepared in different molar ratios. Both solid dispersions and β-cyclodextrin complexes were prepared by solvent evaporation technique. A phase solubility method was used to evaluate the effect of the tested carriers on the aqueous solubility of clotrimazole. The dissolution of all the preparations was tested using the USP paddle method. The selected solid dispersions and inclusion complexes were characterized by differential scanning calorimetry and X-ray powder diffractometry studies, and results clarified the role of the tested carriers in decreasing the crystallinity of clotrimazole and complexing abilities. Based on physical characters and in vitro drug release pattern, polyvinylpyrrolidone solid dispersions (1:1 weight ratio) and ternary cyclodextrin complexes (clotrimazole-β-cyclodextrin complexes with either polymer, 1:1 molar ratio) were selected as ideal batches for suppositories. Suppocire AM/50 mg carbopol 940, was chosen as a suppository base and the suppositories were prepared by molding technique. The prepared suppositories were characterized for weight variation, softening time and drug content. All these properties were found to be ideal. The in vitro drug release pattern was determined in citrate buffer (pH 4.5) containing 1% sodium lauryl sulfate. The in vitro release of clotrimazole from its solid dispersions and inclusion complexes incorporated suppositories was markedly improved when compared to the intact drug incorporated suppositories. Polyvinyl pyrrolidone solid dispersions incorporated suppositories were found to possess excellent antifungal activity.     

不同方法治疗妊娠期外阴阴道念珠菌感染患者的临床疗效对比

目的:探讨不同方法治疗妊娠期外阴阴道念珠菌感染患者的临床疗效。方法:选取2013年10月至2015年10月于我院接受治疗的妊娠期外阴阴道念珠菌感染患者110例,按照治疗方法的不同分为单用组和联用组,每组各55例。其中单用组每晚睡前用小苏打液冲洗阴道外阴后于阴道内放置克霉唑栓,联用组在此基础上加用硝酸咪康唑霜涂擦瘙痒处。两组患者均持续治疗1周。随访患者直至胎儿出生,记录两组患者的临床疗效、复发率、不良反应发生率和新生儿情况并进行对比分析。结果:两组患者经过治疗后,其外阴瘙痒、外阴灼痛和分泌物增多的症状均得到改善,且联合者患者改善得更显著(P0.05);联合组患者的治疗总有效率为92.7%,明显高于单用组的67.2%,差异有统计学意义(P0.05);治疗过程中,两组均有1例患者出现不良反应,但对病程影响不大,且两组患者均顺利分娩出健康新生儿。结论:克霉唑栓联合硝酸咪康唑霜治疗妊娠期外阴阴道念珠菌感染能够明显改善患者临床症状,不影响孕妇分娩和胎儿发育,安全性较高,在临床上值得推广。     

HPLC测定双唑泰阴道泡腾片三组分的含量

目的 建立HPLC法测定双唑泰阴道泡腾片三组分的含量.方法 采用Waters XTerra (R)RP18(250mm×4.6mm,5μm),以甲醇-水-三乙胺(70:30:0.3)(含庚烷磺酸钠10mmol·L-1,用磷酸调pH值至4.0)为流动相,检测波长260nm.结果 甲硝唑、克霉唑和醋酸氯己定分别在0.05～0.5 mg·mL-1、0.04～0.4 mg·mL-1和2～20 μg·mL-1浓度范围内,与峰面积呈良好的相关性(r=0.9999、r=0.9999和r=0.9996),平均回收率为100.3%,RSD为0.38%(n=9);100.3%,RSD为0.48%(n=9);100.3%,RSD为0.67%(n=9).结论 该方法简便、准确、重现性好,可作为该制剂的质量控制标准.     

DNA damage by 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced p53-mediated apoptosis through activation of cytochrome P450/aryl hydrocarbon receptor

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; polycyclic aromatic hydrocarbon) is a persistent and ubiquitous environmental contaminant that causes a wide variety of deleterious effects. In this study, the DNA damage and apoptotic activity induced by TCDD was examined using in silico and in vitro approaches. In silico study showed that conformational changes and energies involved in the binding of TCDD to cytochrome P450 1B1 (CYP1B1) were crucial for its target proteins. Moreover, activated TCDD had high affinity to bind with aryl hydrocarbon receptor (AhR), with a binding energy of −564.7 Kcal/mol. Further, TCDD-CYP1B1 complex showed strong binding affinity for caspase 3, showing a binding energy of −518.5 Kcal/mol, and the docking of caspase inhibitors in the complex showed weak interaction with low binding energy as compared to TCDD-CYP1B1 caspase complexes. Interestingly, TCDD-induced apoptosis was significantly suppressed in Ac-DEVD-CMK-pretreated cells. The DNA damage activity of TCDD was quantified by comet tail formation and γ-H2AX foci formation in HaCaT cells. The role of CYP1B1 and AhR in DNA damage and apoptosis was demonstrated, and clotrimazole as well as knockdown of CYP1B1 and AhR could inhibit TCDD activation and suppress DNA damage followed by apoptosis in HaCaT cells. Moreover, TCDD increased expression of p53 and PUMA and our data showed that TCDD induced DNA damage followed by p53-mediated apoptosis. This study highlights the critical role of CYP1B1 and AhR in TCDD activity and proposes that inhibition of these key molecules might serve as a potential therapeutic approach for treatment of allergy and cancer.     

克霉唑对结肠癌细胞系CCL229生物学行为的影响

目的 研究克霉唑对结肠癌细胞生长,粘附和侵袭转移中的作用,并初步探讨其机制。方法用不同浓度的克霉唑加入培养中的结肠癌细胞株ＣＣＬ２２９中,观察加药前后细胞生长速度的变化,检测细胞与基质的粘附能力,用细胞分离试验测定细胞的同质粘附性。Ｂｏｙｄｅｎ小室法检测细胞的侵袭能力;流式细胞光度术检测细胞尿激酶型纤溶原激活剂（Ｕｒｏｋｉｎａｓｅ－ｔｙｐｅｐｌａｓｍｉｎｏｇｅｎａｃｔｉｖａｔｏｒ,ＵＰＡ）表达。结     

三种局部抗菌药物对甲氧西林耐药金黄色葡萄球菌的抗菌活性研究

目的：研究分析三种局部抗菌药物对甲氧西林耐药金黄色葡萄球菌的抗菌活性研究。方法：回顾性分析我院于2014年3月～2015年3月收治的100例烧伤患者的病历资料,对烧伤创面分泌物制作标本,共分离100株非重复并连续的MRSA,应用棋盘格法对磺胺嘧啶银、莫匹罗星、克霉唑单用以及联用时对MRSA的抗菌活性予以分析。结果：磺胺嘧啶银对MRSA的MIC为8μg/mL, MIC50为9μg/mL,MIC90为16μg/mL,莫匹罗星对MRSA的MIC为2μg/mL,MIC50为16μg/mL,MIC90为64μg/mL,克霉唑对MRSA的MIC分别为2μg/mL,MIC50为3μg/mL,MIC90为4μg/mL。莫匹罗星和克霉唑联用,和磺胺嘧啶银单用比较,MIC50降低75%,MIC90降低87.5%;和莫匹罗星单用比较,MIC50降低87.5%,MIC90降低96.9%;和克霉唑单用比较,MIC50降低50%,MIC90降低50.0%;磺胺嘧啶银和莫匹罗星联用,有70例相同,20例相加,10例无关,没有拮抗现象。磺胺嘧啶银和克霉唑联用,92例抗菌效果相加,8例无关,没有协同和拮抗现象。两种药物联用的抗菌活性明显优于单用。结论：MRSA感染的烧伤创面,就要应用较低剂量的磺胺嘧啶银联合其他药物,不仅可以实现感染的有效控制,也能将药物对创面愈合的一种不良反应降低,值得临床推广。     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

克霉唑诱导急性早幼粒细胞白血病细胞凋亡与钙离子稳态失调和线粒体膜电位的关系

目的:研究钙激活性钾通道阻断剂克霉唑(CLO)诱导人类急性早幼粒细胞白血病(APL)细胞凋亡机制。方法:通过激光扫描共聚焦显微镜实时监测CLO对[Ca2+]i的影响,并观察对内质网钙泵抑制剂Thapsi-gargin的反应,流式细胞仪观察线粒体膜电位,比色法检测caspase-3活性变化。结果:CLO引起[Ca2+]i明显增加,细胞内储存池对Thapsigargin敏感性被克霉唑消除,5μmol/L CLO作用于NB4细胞48h、72h后线粒体膜电位降低,分别是对照组的(1.9±0.1)、(2.1±0.1)倍(P<0.01)。在12h、16h和20h时,caspase-3相对活性与对照组相比分别升高了(1.9±0.2)、(2.7±0.4)、(3.3±0.6)倍。结论:与钙库耗竭有关的胞质内钙离子超载及线粒体膜电位的下降参与钙激活性钾通道阻断剂克霉唑诱导APL凋亡过程。     

甲硝唑联合克霉唑治疗复发性阴道炎的疗效观察

目的:观察甲硝唑联合克霉唑治疗复发性阴道炎的临床疗效。方法:选取我院2009年1月-2011年3月收治的各种复发性阴道炎患者100例,随机均分为对照组与治疗组。对照组给予硝酸咪康唑(达克宁)治疗,治疗组给予口服甲硝唑和阴道外用克霉唑泡腾片治疗,2组均连续治疗14d。比较2组的临床疗效、临床症状、体征改善情况和不良反应发生情况。结果:治疗组对各种类型的复发性阴道炎的临床治愈率、有效率以及复发率均明显优于对照组(P<0.05);治疗组的临床症状与体征改善情况亦明显优于对照组(P<0.05);2组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:口服甲硝唑联合克霉唑泡腾片治疗各种复发性阴道炎的临床疗效确切,不良反应少。