斑蝥素及去甲斑蝥素对小鼠毒性靶器官的影响

目的:比较斑蝥素及去甲斑蝥素对小鼠的毒性作用及两者靶器官损伤程度的差异。方法:取Balb/c小鼠,采用概率单位法计算获得斑蝥素与去甲斑蝥素的半数致死量(median lethal dose,LD_(50))。以1/2 LD_(50)作为毒性研究给药剂量,连续灌胃给药2周。2周后取血检测血清丙氨酸氨基转移酶(ALT),天冬氨酸氨基转移酶(AST),尿素氮(BUN)水平,取肝、肾、小肠和膀胱进行病理组织学观察比较。结果:斑蝥素和去甲斑蝥素LD_(50)分别为2.045,20.966 mg·kg~(-1)。分别以1/2 LD_(50)给药剂量给小鼠灌胃2周后,血清学检测结果表明,与正常组比较,斑蝥素组无显著差异;去甲斑蝥素可导致ALT,BUN水平显著性升高。肝、肾病理结果表明,与正常组比较,斑蝥素组肝肾轻微病变,去甲斑蝥素组可见肝脏炎性细胞浸润,肝细胞空泡变样,肾小球和小管弥漫性损伤。小肠病理结果表明,斑蝥素组导致肠道淋巴结肿大并分叶,去甲斑蝥素组症状较轻。膀胱病理表明,斑蝥素组发现血管炎症、膀胱移行上皮或黏膜层炎症反应,去甲斑蝥素组轻微移行上皮炎症反应。结论:临床前动物模型结果表明,去甲斑蝥素的毒性主要表现在肝脏和肾脏,斑蝥素的毒性作用主要表现为小肠和膀胱。     

斑蝥素乳膏含量测定方法的改进

目的：重新建立斑柔素乳膏含量测定方法。方法：利用斑蝥素的溶解性,采用热碱溶解、冷却与基质分离,酸化后氯仿提取,再用部分颁标准上的气相色谱条件,测定斑蝥素乳膏中斑蝥素的含量。结果：回收率为100．4％。RSD＝1．9％。结论：方法准确、快速、可完全除去基质干扰。     

斑蟊素注射液的含量测定

薄层层析表明,斑蟊素注射液中含有斑蟊素和斑蟊酸钠。这二种成份与盐酸于60℃水浴恒温反应30min后,用无水乙醇溶解,再稀释成95％乙醇溶液,在波长225nm处有最大吸收,且在0.1～1.0mg/ml范围内符合比尔定律。可用紫外分光光度法测定注射液的总含量。其平均回收率为99.89％,cv为0.12％。     

中药斑蝥不同炮制品总斑蝥素含量的比较

目的: 建立测定不同斑蝥炮制品及斑蝥虫体各部位中总斑蝥素的含量的方法,探讨炮制对总斑蝥素的影响。 方法: HPLC,以甲醇-水(23∶ 77)为流动相,柱温35 ℃,流速为1 mL ·min^-1,检测波长为230 nm。 结果: 斑蝥总斑蝥素含量远高于药典规定。样品中总斑蝥素含量:生斑蝥饮片＞斑蝥药材＞米炒斑蝥。头足翅中总斑蝥素的总含量为0.61%。 结论: 应以总斑蝥素含量控制斑蝥饮片质量。     

The phosphoprotein phosphatase family of Ser/Thr phosphatases as principal targets of naturally occurring toxins

Phosphoprotein phosphatases (PPPs) constitute one of three otherwise unrelated families of enzymes that specialize in removing the phosphate group from phosphorylated serine and threonine residues. The involvement of PPP enzymes in the regulation of processes such as gene expression, DNA replication, morphogenesis, synaptic transmission, glycogen metabolism, and apoptosis has underscored their potential as targets for the treatment of a variety of conditions such as cancer, diabetes, or Alzheimer’s disease. Interestingly, PPP enzymes also constitute the physiological target of multiple naturally occurring toxins, including microcystins from cyanobacteria and cantharidin from beetles. This review is devoted to the PPP family of enzymes—with a focus on the human PPPs—and the naturally occurring toxins that are known to potently impair their activity. The interaction of the toxins with the enzymes is evaluated in atomic detail to obtain insight on two complementary aspects: (1) which specific structural differences within the similarly folded catalytic core of the PPP enzymes explain their diverse sensitivities to toxin inhibition and (2) which structural features presented by the various toxins account for the differential inhibitory potency towards each PPP. These analyses take advantage of numerous site-directed mutagenesis studies, structure-activity evaluations, and recent crystallographic structures of PPPs bound to different toxins.     

Antiparasitic Effects of Potentially Toxic Beetles (Tenebrionidae and Meloidae) from Steppe Zones

Arthropods and specifically beetles can synthesize and/or sequester metabolites from dietary sources. In beetle families such as Tenebrionidae and Meloidae, a few studies have reported species with toxic defensive substances and antiparasitic properties that are consumed by birds. Here we have studied the antiparasitic activity of extracts from beetle species present in the habitat of the Great Bustard (Otis tarda) against four pathogen models (Aspergillus niger, Meloidogyne javanica, Hyalomma lusitanicum, and Trichomonas gallinae). The insect species extracted were Tentyria peiroleri, Scaurus uncinus, Blaps lethifera (Tenebrionidae), and Mylabris quadripunctata (Meloidae). M. quadripunctata exhibited potent activity against M. javanica and T. gallinae, while T. peiroleri exhibited moderate antiprotozoal activity. The chemical composition of the insect extracts was studied by gas chromatography coupled with mass spectrometry (GC-MS) analysis. The most abundant compounds in the four beetle extracts were hydrocarbons and fatty acids such as palmitic acid, myristic acid and methyl linoleate, which are characteristic of insect cuticles. The presence of cantharidin (CTD) in the M. quadripunctata meloid and ethyl oleate (EO) in T. peiroleri accounted for the bioactivity of their extracts.     

斑蝥素对大鼠颈动脉球囊损伤后新生内膜增生的影响

目的:通过细胞培养及建立大鼠颈动脉球囊损伤模型,探讨斑蝥素对血管内皮损伤后新生内膜增生的作用及机制。方法:采用组织块贴壁法体外培养SD大鼠胸主动脉血管平滑肌细胞(VSMC),以脂多糖(LPS)作为刺激因素,选择吡咯烷二硫代氨甲基甲酸盐(PDTC)作为核转录因子(NF-κB)信号通路抑制剂,将VSMC分为对照组、1μg/ml LPS刺激组(LPS组)、LPS刺激后加用5μmol/L斑蝥素组(斑蝥素组)、LPS刺激后加用80μmol/L PDTC处理组(PDTC组)、LPS刺激后加用5μmol/L斑蝥素和80μmol/L PDTC处理组(斑蝥素+PDTC组)共5组;应用伤口愈合实验和Transwell实验检测斑蝥素对VSMC迁移的影响,蛋白免疫印迹法(Western blot)检测斑蝥素对NF-κB p65、磷酸化NF-κB p65(p-p65)和基质金属蛋白酶9(MMP-9)表达的影响。采用Fogarty(2 F)球囊导管建立大鼠颈动脉球囊损伤模型,SD大鼠随机分为假手术组、损伤组、斑蝥素(2 mg/kg)组,各组于造模前1周开始腹腔注射给药,连续给药3周,术后14 d取血检测血清肿瘤坏死因子α(TNF-α)及白细胞介素-6(IL-6)的水平,同时取损伤颈动脉进行苏木精-伊红染色、免疫组织化学法检测MMP-9、NF-κB p65、TNF-α及IL-6的表达。结果:伤口愈合实验和Transwell实验结果显示,LPS组细胞的迁移能力显著增强(P<0.01);与LPS组比较,斑蝥素组、PDTC组、斑蝥素+PDTC组细胞迁移能力均受到抑制(P<0.01),另外与斑蝥素组比较,斑蝥素+PDTC组细胞迁移未见差异(P>0.05)。Western blot结果显示,与对照组比较,LPS组细胞p-p65和MMP-9表达增加,斑蝥素组或PDTC组表达显著降低(P均<0.05);与斑蝥素组比较,斑蝥素+PDTC组中p-p65和MMP-9表达未见差异(P均>0.05)。在大鼠颈动脉球囊损伤模型中,损伤组大鼠血清内TNF-α和IL-6浓度明显升高,斑蝥素组大鼠血清中TNF-α和IL-6浓度较损伤组显著降低(P均<0.05);损伤组大鼠颈动脉内膜增生明显,斑蝥素组较损伤组内膜面积、内膜面积/中膜面积减小(P均<0.05);与损伤组比较,斑蝥素组血管内膜中MMP-9、NF-κB p65、TNF-α和IL-6的表达明显降低(P均<0.05)。结论:斑蝥素对LPS诱导的VSMC的迁移以及对受损大鼠颈总动脉内膜的增生具有显著的抑制作用;其机制主要与抑制NF-κB信号通路介导的炎症反应密切相关。     

Safety and effectiveness of cantharidin–podophylotoxin–salicylic acid in the treatment of recalcitrant plantar warts

The aim of our study was to evaluate the efficacy and safety of topical cantharidin–podophylotoxin–salicylic acid (CPS) treatment of recalcitrant plantar warts (RPW). This study was carried out in a health center in the city of A Coruña (Spain) between January and December 2013. A total of 75 patients completed all the stages of the research process. Information related to treatment with CPS and adverse effects was abstracted from medical records. Of 93 potential patients identified, 75 had at least one follow‐up visit or telephone call after treatment and were included in this study. Patients experienced an average of 5.4 visits until complete resolution of their plantar wart occurred, although CPS was not applied at every visit. Fifty‐four patients required one application to eliminate the wart and 21 patients required two applications/patient. Seventy‐seven percent of patients experienced blistering – an expected therapeutic side effect. All patients experienced some form of an adverse event, the most common being pain (81.3%) and significant blistering (15%). Other side effects were rare (18.7%) and included pruritus, possible mild infection, significant irritation, and bleeding. All patients reported treatment, supporting our results that CPS is a safe and efficacious treatment modality for RPW and should be considered when symptomatic infection necessitates treatment.     

Safety and Efficacy of VP-102 (Cantharidin, 0.7% w/v) in Molluscum Contagiosum by Body Region: Post hoc Pooled Analyses from Two Phase III Randomized Trials

Trial Registration>ClinicalTrials.gov identifier nos. {"type":"clinical-trial","attrs":{"text":"NCT03377790","term_id":"NCT03377790"}}NCT03377790 (for CAMP-1) and {"type":"clinical-trial","attrs":{"text":"NCT03377803","term_id":"NCT03377803"}}NCT03377803 (for CAMP-2).BackgroundVP-102 is drug-device combination product containing cantharidin (0.7% w/v) and has undergone Phase III clinical trials for the treatment of molluscum contagiosum (molluscum). Efficacy and safety may differ by body region due to variable skin anatomy. ObjectiveWe investigated the pooled safety and efficacy of VP-102 by affected body region.MethodsIndividuals at least two years of age with molluscum were randomized to topical VP-102 or vehicle once every 21 days until clear (maximum of four applications). Participants were assigned to body region groups where lesions were present at baseline. Body region lesion counts were recorded at each visit. Efficacy was measured by the percentage of participants with complete clearance of lesions by region. Pre-specified adverse events (AEs) were analyzed for those treated in the region on that visit.ResultsParticipants had a mean of two regions affected at baseline. Complete clearance was significantly higher in the VP-102-treated group than with vehicle application in all regions at the last visit (P<0.01 for each region). The incidence of pre-specified AEs was consistent across regions. However, these analyses were post hoc, and individual lesions were not tracked for efficacy.Conclusion VP-102 treatment shows consistent safety and efficacy across molluscum body regions.     

Real‐life treatment of cutaneous warts with cantharidin podophyllin salicylic acid solution

Patients often request treatment of their burdensome cutaneous warts. However, a safe and effective treatment for cutaneous warts is lacking. This study evaluates treatment outcome, side effects, and patient satisfaction after topical application of cantharidin 1% podophyllin 2% salicylic acid 30% (CPS1) solution in a large series of children and adults with cutaneous warts. Fifty‐two children and 83 adults with warts, treated with CPS1 solution between October 2012 and October 2014, were included. Complete clearance of warts occurred in 86.5% of children and 62.7% of adults treated with CPS1 solution (p < .01). Resolution of warts was partial in 3.9 and 24.1% and absent in 9.6 and 13.2% of children and adults respectively. Side effects were present in 41.2% of children and 46.3% of adults (p = .7). Most common side effects were blistering, pain, and burning sensation. No serious adverse events occurred. On a 10‐point scale, median patient satisfaction score was 9.0 (interquartile range 7.8–10.0) and 8.0 (interquartile range 5.1–9.7) for children and adults respectively (p < .01). CPS1 solution is a safe and promising treatment modality with a high clearance and high patient satisfaction rate for the management of cutaneous warts, particularly in children.