3种青蒿素衍生物对日本血吸虫吡喹酮抗性株童虫的体内作用效果观察

目的观察3种青蒿素衍生物双氢青蒿素、青蒿琥酯和蒿甲醚对日本血吸虫吡喹酮抗性株童虫的体内作用效果。方法以经11轮亚治疗剂量吡喹酮筛选的日本血吸虫为吡喹酮抗性株,以未暴露于吡喹酮的日本血吸虫作为吡喹酮敏感株,收集2虫株尾蚴感染小鼠,以300mg/kg双氢青蒿素、青蒿琥酯和蒿甲醚对感染后7~8 d童虫分别进行2次灌服用药(总剂量600 mg/kg),所有小鼠于感染后45 d解剖,收集小鼠体内成虫并计数,计算减虫率和减雌率。结果 300 mg/kg双氢青蒿素、蒿甲醚和青蒿琥酯2日疗法(总剂量600 mg/kg)对日本血吸虫吡喹酮敏感株7~8 d童虫的减虫率为69.8%~71.0%,减雌率为75.4%~79.8%;对日本血吸虫吡喹酮抗性株7~8 d童虫的减虫率为64.6%~66.1%,减雌率为69.3%~71.1%,差异均无统计学意义(均p0.05)。结论 日本血吸虫吡喹酮抗性株对青蒿素类衍生物双氢青蒿素、青蒿琥酯和蒿甲醚依然敏感,青蒿素衍生物与吡喹酮在日本血吸虫中不存在交叉抗药性。     

青蒿琥酯预防曼氏血吸虫病的实验研究

目的　研究青蒿琥酯对小鼠曼氏血吸虫病的预防作用及优化给药方案。　方法　小鼠尾部接触感染曼氏血吸虫尾蚴后口服青蒿琥酯 ,灌注法收集计数虫体数和雌虫数 ,镜检计数肝脏和肠的虫卵 ,统计减虫率、减雌率和平均产卵量 ,分析青蒿琥酯不同给药时间、剂量、疗程的预防效果。　结果　青蒿琥酯预防小鼠曼氏血吸虫病的最佳剂量为 3 0 0mg/kg ,14、2 1d童虫对药物最为敏感 ,减虫率分别为 84%和 93 %。小鼠感染 14d后每周口服 1次青蒿琥酯3 0 0mg/kg ,连续 4wk ,减虫率达 99% ;感染 14或 2 1d后每 2wk口服 1次青蒿琥酯 3 0 0mg/kg ,连续 4wk ,减虫率达 97%或 96%。各服药组平均产卵量与对照组差异具有显著性意义　结论　青蒿琥酯可杀灭曼氏血吸虫童虫 ,影响雌虫发育产卵 ,有效预防曼氏血吸虫病。建议应用青蒿琥酯预防曼氏血吸虫病的给药方案为感染 14或 2 1d后首服 ,每 1或 2周服用 1次。     

青蒿琥酯和吡喹酮防治血吸虫病相互作用的研究

本文就血吸虫病防治药青蒿琥酯与血吸虫病防治药吡喹酮的相互作用进行了初步探讨，实验结果表明：小鼠口服青蒿琥酯３００μｇ／ｋｇ对第７天、第８天的童虫有杀灭作用，减虫率为７１．６％，减雌率为７２％；口服吡喹酮３００ｍｇ／ｋｇ对第７天童虫无效，对第３０天成虫有明显杀灭作用，减虫率为７２％，减雌率为７８．３％；青蒿琥酯与吡喹酮同时服，或者先服吡喹酮后服青琥酯均明显影响青琥酯的杀童虫作用；先服青蒿琥酯而后服吡     

三苯双脒、青蒿琥酯、蒿甲醚和吡喹酮单剂、多剂或联合用药治疗大鼠华支睾吸虫感染的实验研究

目的 观察三苯双脒、青蒿琥酯、蒿甲醚、或吡喹酮单剂、多剂给药,及其伍用治疗感染华支睾吸虫大鼠的疗效。 方法 147只SD大鼠各感染50个华支睾吸虫囊蚴,于感染后42～44 d分组治疗。各药物采用灌胃给药。①60只感染大鼠随机分为11组（每组4～5只）,分别为三苯双脒150 mg/kg（顿服）、75 mg/（kg·d）×2 d、50 mg/（kg·d）×3 d和25 mg/kg（tid）×2 d组;吡喹酮150 mg/kg（顿服）、75 mg/（kg·d）×2 d和25 mg/kg（tid）×2 d;青蒿琥酯或蒿甲醚75 mg/kg（顿服）和37.5 mg/（kg·d）×2 d组。②另87只感染大鼠随机分为15组（每组4～6只）,用青蒿琥酯或蒿甲醚（30 mg/kg）分别与吡喹酮（150 mg/kg）、三苯双脒（50 mg/kg和75 mg/kg）伍用组;三苯双脒（50 mg/kg）与吡喹酮（150 mg/kg）伍用组;三苯双脒（75 mg/kg）与吡喹酮（187.5 mg/kg）伍用组,及各药的单用组。并设同批感染未治疗对照组。受治鼠于治疗后2周剖杀,收集胆管和肝组织内的残留华支睾吸虫,计算各组的平均虫数和减虫率,用非参数统计方法（Mann-Whitney秩和检验）对相应组间的平均虫数进行分析。 结果 感染华支睾吸虫的大鼠口服单剂三苯双脒或吡喹酮（150 mg/kg）的减虫率分别为57.2%和63.8%。三苯双脒各小剂量多次给药组的减虫率稍高,达77.1%～79.4%,而吡喹酮小剂量多次给药组的减虫率则为50.6%～54.2%。但两种药物各组间的平均虫数的差异无统计学意义。青蒿琥酯和蒿甲醚各单剂给药组与小剂量多次给药组的减虫率均较高,分别为90.4%～98.5%和100%。三苯双脒小剂量（50或75 mg/kg）与吡喹酮（150 mg/kg 或187.5 mg/kg）伍用治疗,减虫率为74.9%～100%,高于其各单药组的减虫率（26.9%～79.6%）。青蒿琥酯或蒿甲醚小剂量（30 mg/kg）与吡喹酮（150 mg/kg）或三苯双脒（50或75 mg/kg）伍用治疗,减虫率为74.9%～97.9%,亦高于其各药组的减虫率（24.8%～79.6%）。 结论 青蒿琥酯、蒿甲醚、吡喹酮和三苯双脒均为有效的抗华支睾吸虫药物,各药物小剂量伍用具有增效作用。     

青蒿琥酯对日本血吸虫生殖作用的影响

目的观察青蒿琥酯对日本血吸虫成虫生殖的影响。方法小鼠感染日本血吸虫尾蚴后第20d灌服青蒿琥酯300mg/kg,给药后3周解剖小鼠,用灌注法收集成虫,计算减虫率;取肝右叶做石蜡切片,观察虫卵肉芽肿;剩余肝脏溶解后计数虫卵;收集无损虫体进行体外培养,观察虫卵形态,并计数产卵量;取完好的虫体做石蜡切片,HE染色后镜下观察生殖器官的发育。结果给药组小鼠体内雌虫产卵量与对照组存在显著的差异,体外培养结果与体内产卵结果相一致。给药组小鼠体内的雌虫的卵巢发育缓慢,比对照组的小,且卵巢内多为未成熟的卵细胞。结论青蒿琥酯能抑制雌虫卵巢的发育,降低或抑制雌虫的产卵量,具有抗日本血吸虫雌虫生殖的作用,能有效的减轻血吸虫病的病情和控制传播。     

感染日本血吸虫小鼠用双氢青蒿素连续给药及与吡喹酮伍用的疗效观察

目的观察双氢青蒿素连续多次给药及与吡喹酮伍用对日本血吸虫童虫和成虫的杀灭效果。方法采用腹部贴片感染小鼠,每鼠感染日本血吸虫尾蚴(40±1)条后随机分组。分别在感染后第6天或第34天,用双氢青蒿素200、300、400mg/kg或600mg/kg灌服治疗,日1次,连服3d。在小鼠感染后第7天或第35天,分别灌服双氢青蒿素或吡喹酮各300mg/kg以及2种药物剂量同时灌服,或双氢青蒿素于小鼠感染后第7天或第35天灌服,而吡喹酮则在感染后第6天或第8天,以及第34天或第36天给药。2次试验各设有1组不治疗的对照。治疗组和对照组小鼠均于感染后50d解剖,收集成虫,计算减虫率和减雌率。结果在感染后第6天,连续3次灌服剂量分别为200、300、400mg/kg和600mg/kg双氢青蒿素,小鼠减虫率分别为69.16%、80.68%、87.11%和90.62%,减雌率分别为62.19%、75.61%、83.65%和92.16%。在感染后第34天,连续3次灌服给药组小鼠减虫率分别为73.90%、74.99%、84.19%和85.49%,减雌率分别为83.84%、92.91%、94.05%和95.27%。在童虫期(感染后7d),单剂量双氢青蒿素(300mg/kg)与吡喹酮(300mg/kg)联合给药组小鼠减虫率为19.66%;单剂量双氢青蒿素(300mg/kg)第7天服用,吡喹酮第6天或第8天给药组小鼠减虫率分别为42.96%和57.46%。在成虫期(感染后35d),双氢青蒿素(300mg/kg)与吡喹酮(300mg/kg)联合给药组小鼠减虫率为70.21%,吡喹酮第34天或第36天给药组小鼠减虫率分别为60.82%和81.51%。结论双氢青蒿素在童虫期和成虫期连续给药可增强其抗日本血吸虫作用效果。在童虫期,双氢青蒿素与吡喹酮伍用或吡喹酮第6天用药可降低抗日本血吸虫作用效果;在成虫期,双氢青蒿素与吡喹酮伍用或吡喹酮第36天用药可增强抗日本血吸虫效果。     

蒿苯酯预防日本血吸虫病的实验研究

本文报道了蒿苯酯预防动物血吸虫病的实验结果。小鼠、免及犬在单次感染日本血吸虫尾蚴后第7d开始服蒿苯酯,每wkl次,连服4-6次,对宿主体内的血吸虫童虫有明显杀灭效果,减虫率达90％—100％,该药对不同感染度小鼠体内血吸虫童虫的杀灭作用相同。对连续感染14d(每d1次)的家兔减虫率亦达93.5％,蒿苯酯皮下注射给药效果比口服好,但毒性大。比较蒿苯酯、呋喃丙胺和吡喹酮3种药物杀灭血吸虫童虫的效果,以蒿苯酯为最佳。同样,蒿苯酯优于其他两种青蒿衍生物一蒿甲醚和还原青蒿素。     

青蒿琥酯对日本血吸虫作用的研究小鼠体内不同发育阶段虫体对青蒿琥酯的敏感性

目的观察小鼠体内不同发育阶段日本血吸虫童虫与成虫对青蒿琥酯的敏感性。方法用定量日本血吸虫尾蚴感染小鼠,感染2h,1、3、7、12、14、16、25、35d和42d分别一次性灌服500mg/kg青蒿琥酯。给药后4周解剖小鼠,采用门静脉灌注法收集虫体,计算减虫率。结果青蒿琥酯对1、3、7、12、14、16、25、35、42d龄童虫或成虫的减虫率分别为16.9%、18.0%、71.3%、50.2%、36.9%、31.3%、45.3%、58.0%、26.4%,其中以7~35d龄虫对该药最敏感。结论青蒿琥酯对小鼠体内日本血吸虫不同发育阶段均有杀灭作用,对7~35d龄虫体杀灭效果更为明显。     

蒿甲醚和青蒿琥酯对感染曼氏血吸虫小鼠治疗作用的初步研究

目的了解蒿甲醚和青蒿琥酯对小鼠曼氏血吸虫作用的效果.方法将小鼠随机分成12个实验组及1个对照组,以皮下注射的方法,每鼠接种约80条尾蚴,接种尾蚴46 d后,分别以蒿甲醚或青蒿琥酯灌胃治疗,第1天,分别以400、300、200 mg/kg的剂量1次灌胃;第2～7天,则每天分别按以上剂量的半量灌胃,7 d灌胃的总剂量分别为1 600、1 200、800 mg/kg.总量1剂组,在第7天,分别按1 600、1 200、800 mg/kg剂量1次灌胃.另设感染阳性对照组,不加治疗. 结果蒿甲醚7日疗法1 600、1 200、800 mg/kg剂量组减虫率分别为53.0%、49.0%和53.0%,减雌率为78.0%～82.0%,总量1剂组效果与7日疗法基本相同.青蒿琥酯7日疗法相应剂量减虫率分别为16.0%、37.0%和49.0%.结论蒿甲醚和青蒿琥酯对小鼠曼氏血吸虫具有一定的杀虫效果,蒿甲醚在疗效和毒性方面稍佳.     

青蒿琥酯抗日本血吸虫童虫和成虫作用的研究

目的 观察青蒿琥酯对不同阶段日本血吸虫的损害作用,揭示青蒿琥酯的杀虫机制.方法小鼠感染尾蚴18 d时给予青蒿琥酯300 mg/kg,24 h后灌注法收集童虫,并用紫外吸收法和Bradford标准曲线法测定青蒿琥酯对日本血吸虫18 d童虫DNA和蛋白质含量的影响;分别将10条虫体在含有3H胸腺嘧啶核苷的培养基中培养24 h后,用滤膜法和匀浆法测定青蒿琥酯对标记核苷掺入童虫DNA的影响;感染血吸虫尾蚴21 d的小鼠一次性灌服青蒿琥酯300 mg/kg,给药后21 d,灌注法收集成虫,观察青蒿琥酯对日本血吸虫成虫生殖器官大小及生殖细胞发育的影响;小鼠感染血吸虫33 d时给予同样的青蒿琥酯进行治疗,24 h和48 h后处死小鼠,将肝脏制作组织切片,在光镜下观察同等剂量青蒿琥酯引起的成虫肝移和形态学变化的影响.结果 青蒿琥酯体内作用18 d的虫体,24 h后,童虫的DNA和蛋白质含量均较对照组明显减少,减少率分别为23.0%和33.6%(P＜0.01);在含有3H胸腺嘧啶核苷的培养基中培养24 h后,童虫摄入标记的核苷及核苷掺入童虫DNA的量较对照组也明显减少,减少率分别为61.1%和40.8%(P＜0.01);21 d给药组小鼠体内雌虫卵巢的成熟、发育受到了抑制;药物作用于虫体33 d后能明显引起虫体形态的变化,特别是虫体体表.结论 青蒿琥酯能减少日本血吸虫童虫蛋白质和DNA的含量,能明显抑制虫体对标记核苷的摄入以及标记核苷掺入虫体DNA的量,能引起虫体体表明显的组织形态学变化,并且能抑制雌虫卵巢的发育,降低或抑制雌虫的产卵,能有效减轻血吸虫病的病情和控制传播.     

Strikes, flooding, rats, and leptospirosis in Marseille, France

Objectives

The aim of this study was to examine the mechanisms by which weather conditions, the incidence of Leptospira in reservoir populations, and various socio-ecological factors are driving the emergence of leptospirosis in Marseille, France.

Methods

Over the last 30 years our laboratory has surveyed all human cases of leptospirosis in Marseille using clinical, epidemiological, serological, and molecular tools. Data for the weather conditions in Marseille were collected from the official meteorological station, and garbage management strikes were monitored through the local press. Rats were trapped in alleys near to where the patients may have acquired leptospirosis.

Results

Three new cases of autochthonous leptospirosis are reported. The global tendency for rainfall showed a slight increase over the period under analysis. The index case of leptospirosis occurred after a heavy rainfall with flooding. Over the last 10 years Marseille has undergone 82 days of garbage management strikes. Leptospira DNA was detected in two of 11 rats.

Conclusions

The emergence of leptospirosis has become a public health problem in Marseille, and is associated with a combination of heavy rainfall and garbage collection strikes in which garbage is left on the street and thereby contributes to the expansion of the rat population on the surface.     

Syphilis, chlamydia, and gonorrhea screening in HIV-infected patients in primary care, San Francisco, California, 2003

The Centers for Disease Control (CDC) recommends sexually transmitted disease (STD) screening among HIV-infected persons in order to reduce HIV transmission. We evaluated the results of routine screening for syphilis and for urogenital, pharyngeal, and rectal gonorrhea (GC) and chlamydia (CT) among asymptomatic HIV-infected patients at an HIV primary care clinic in San Francisco, California. We found 15 new syphilis infections of 814 tested (1.8%) and 60 new cases of CT or GC infection of 586 tested (10.2%), with 88% of GC and CT infections occurring at nonurethral sites. Our study reveals a high rate of asymptomatic STDs among HIV-infected patients in primary care and supports the CDC recommendations to screen HIV-infected patients for STDs at all relevant anatomic sites.     

Zinc, iron, copper, selenium, lactoferrin, and ferritin in human pus

BACKGROUND: Restriction of zinc and iron available for microbial growth in tissues are well-recognized host defense mechanisms. The present studies were performed to characterize some constituents of human pus that may affect these important host defenses. METHODS: Zinc, iron, copper, calcium, and magnesium in pus were measured using an atomic absorption spectrophotometer; selenium was measured fluorometrically. Ferritin was measured with a fluorometric enzyme immunoassay, and lactoferrin was measured with a radial diffusion assay. The growth of Escherichia coli at 37 degrees C was measured in pus supernate adjusted to pH 5.5 or 7.4, in boiled supernate, or in supernate adjusted with 1.3 mM iron or 0.9 mM zinc singly or together. RESULTS: Zinc and iron concentrations in pus exceeded normal serum. Calcium and magnesium levels were 2- to 3-fold lower and higher, respectively, than normal serum values. Lactoferrin concentrations of were 880 +/- 48 microg/mL and ferritin levels were 20,726 +/- 2,667 ng/mL. Growth of an E coli strain was inhibited in pus at pH 5.5 but not at pH 7.4, and growth was enhanced by addition of iron or zinc to E coli suspended in pus at pH 6.7. CONCLUSIONS: To our knowledge, this is the first report of the zinc, iron, copper, selenium, lactoferrin, and ferritin levels of human pus. These studies provide additional insight into host defense mechanisms mediated by the restriction of the bioavailability of zinc and iron in suppurative infection.     

Prevalence,Self-Awareness,Treatment, and Control of Hypertension in Lhasa,Tibet

To investigate the prevalence, self-awareness, and treatment of hypertension in Lhasa, Tibet, a total of 1370 native Tibetan aged ≥18 years were selected, using stratified proportional sampling. The study showed that the prevalence of hypertension was 51.2%, significantly higher in men (56.0%) than in women (48.0%) (P = .004). The hypertension prevalence increased with increasing age (77.8% in 60–74 y and 82.5% in ≥75 y groups) and was higher in urban, suburban, or agricultural area than in pastoral area (P < .001). The self-awareness, treatment, and control rate of hypertension were 63.5%, 24.3% and 7.7%, respectively. In multivariable regression analysis, age, urban residence, amount of daily intake of fat and oil, and body mass index <18.5 kg/m² were independently associated with hypertension. In conclusion, hypertension was highly prevalent among native Tibetan people in Lhasa, and the rates of self-awareness, treatment, and control of hypertension were low.