大鼠多器官彗星试验方法的验证研究

目的:采用对氯苯胺、氯化钠、对乙酰氨基酚和庆大霉素4个不同作用机制的化合物,对已建立的大鼠多器官(肝、胃和肾)彗星试验方法进行验证。方法:SD雄性大鼠分别在0、24和45 h经口灌胃不同剂量的对氯苯胺[37.5、75和150 mg/(kg·d)]、氯化钠[500、1 000和2 000 mg/(kg·d)]、对乙酰氨基酚[20、100和500 mg/(kg·d)],或肌肉注射庆大霉素[20、40和80 mg/(kg·d)],各组均设置溶剂对照品,以及在24和45 h经口灌胃阳性对照甲基磺酸乙酯[EMS,200 mg/(kg·d)],所有动物在末次给予受试物约3 h后经戊巴比妥钠麻醉放血处死,制备肝脏、胃和肾脏单细胞悬液后制片,再经裂解、解旋、电泳、中和、染色以进行彗星显像分析;对乙酰氨基酚处理的大鼠肝脏和庆大霉素处理的大鼠肾脏经10%福尔马林溶液固定后进行组织病理学检查。结果:与溶剂对照组比较,对氯苯胺处理组大鼠肝、胃和肾的尾部DNA百分率增加,并呈剂量-反应关系(P<0.05);氯化钠、对乙酰氨基酚和庆大霉素处理组大鼠肝、胃和肾的尾部DNA百分率与溶剂对照比较,差异均无统计学意义(P均>0.05);对乙酰氨基酚各剂量组动物出现肝脏不同程度的肝脏细胞炎症反应或细胞坏死等病理学改变。结论:本研究采用已知遗传毒性化合物、有和无靶器官毒性的非遗传毒性化合物,验证了多器官(肝、胃和肾)彗星试验方法具有很好的灵敏度和特异性,有望为体内碱性彗星试验方法在新药遗传毒性评价领域的推广提供技术参考。     

蒿甲醚对小鼠结直肠癌的抑瘤及抗血管生成的实验研究

目的:探讨蒿甲醚(Artemether)对BALB/c小鼠CT-26 结直肠癌的抑瘤及抗血管生成作用.方法:BALB/c小鼠皮下接种CT-26 结直肠癌细胞(2×10 6 mL -1)48只,雌、雄各半;随机分为6组,每组8只,分别为低剂量33.3 mg/(kg·d)、中剂量50 mg/(kg·d)、高剂量66.6 mg/(kg·d)和中剂量50 mg/(kg·d)加铁剂1.5 mg/(kg·d)组、阳性对照组为顺铂5 mg/(kg·d)、空白对照组为等体积生理盐水;均在接种5 d后,顺铂采用腹腔注射15 d停药,其余采用灌胃法持续给药15 d,每天1次,末次给药24 h后,处死动物.用Steel公式计算肿瘤体积V(mm 3)=0.5 ab 2.采用免疫组化方法检测移植瘤组织微血管密度.结果:各治疗组抑瘤率分别为42.3%、51.4%、52.0%和53.5%;血管计数分别为13±6、31±4、38±5和11±9,生理盐水对照组为49±9;各治疗组微血管密度均明显低于生理盐水对照组(分别P＜0.05,P＜0.01);移植瘤体积较对照组显著减小.结论:在一定剂量范围内,口服蒿甲醚对小鼠CT-26结直肠癌移植瘤有明显的抑制作用;与铁剂合用能使抑瘤率增加;在具有抑瘤作用的同时,蒿甲醚还具有明显抑制小鼠结直肠癌移植瘤血管生成作用.     

雷公藤多甙对雄性小鼠生殖细胞毒性的研究

背景与目的： 研究雷公藤多甙对雄性小鼠生殖细胞的遗传毒性作用,为临床将雷公多甙藤作为抗生育剂和治疗药的安全使用提供理论基础和依据。 材料与方法： 昆明种雄性小鼠共30只,随机分成阴性、阳性对照组,雷公藤多甙抗生育剂量组[10 mg/(kg·d)]、中间剂量组[20 mg/(kg·d)]和治疗剂量组[30 mg/(kg·d)],共5组,每组6只。分别采用骨髓微核实验、精子畸形实验、染色体畸变实验和联会复合体技术,研究雷公藤多甙对雄性小鼠生殖细胞的遗传毒性。 结果： 雷公藤多甙20和30 mg/(kg·d)剂量组可产生体细胞遗传毒性, 与阴性对照组比较差异具有统计学意义(P<0.05)。雷公藤多甙3个剂量组均可致精子畸形并对初级精母细胞产生损伤,以及具有生殖细胞联会复合体损伤,与阴性对照组比较差异均具有统计学意义(P均<0.05)。 结论： 雷公藤多甙具有遗传毒性和生殖细胞毒性,生殖细胞对雷公藤多甙的敏感性高于体细胞,作为治疗药物忌大剂量长时间使用。     

钬元素对小鼠肝脏细胞DNA损伤的影响

背景与目的: 通过研究钬离子溶液对小鼠肝脏细胞DNA的损伤,探讨钬元素对诱导动物细胞凋亡的影响 。材料与方法: 处理组1： 小鼠定时灌胃氯化钬溶液50 mg/(kg•d),连续5 d; 组 2～3： 小鼠分别定时腹腔注射氯化钬溶液60 mg/(kg•d)和120 mg/(kg•d),连续2 d; 组4： 小鼠一次性腹腔注射氯化钬溶液320 mg/kg; 每次染毒相间24 h,组1～4： 小鼠均在末次染毒24 h后处死,提取肝脏DNA。 组5： 小鼠一次性腹腔注射等体积生理盐水; 组6～9： 小鼠一次性腹腔注射氯化钬溶液80 mg/kg,分别于注射后12、24、48和96 h处死小鼠提取肝脏DNA。通过琼脂糖凝胶电泳研究各组DNA带型变化。 结果：处理组7 DNA电泳中出现连续的弥散带型,其它各组均未观察到明显的拖尾现象。也未观察到“DNA ladder"。 结论： 钬离子对小鼠肝脏细胞DNA的断裂作用可能与其剂量大小、处理时间及DNA修复作用有关,而且无特异性。本实验结果表明,钬元素未诱导小鼠肝脏细胞凋亡。     

实验性癌性恶病质的发生及其干预

目的初步探讨促炎细胞因子IL-6、TNF-α在癌性恶病质(CC)形成中的作用并观察不同剂量吲哚美辛(indomethaein,IN)对CC改善效果。方法将鼠结肠腺癌26(colon26)细胞株皮下接种于BALB/c小鼠,构建CC模型。将68只BALB/c小鼠随机分成5组:健康对照组、恶病质 等渗盐水对照组、恶病质 IN 0.5mg/(kg·d)组、恶病质 IN 1.0mg/(kg·d)组、恶病质 IN 2.0mg/(kg·d)组。监测各组小鼠一般情况、去瘤体重、血清IL-6、TNF-α的水平、各生化指标浓度变化、肿瘤组织中bcl-2的表达及癌细胞的凋亡和增殖等情况。结果恶病质小鼠去瘤体重明显下降(P<0.05),血清各生化指标不同程度的出现代谢消耗状态(P<0.05),血清IL-6,TNF-α水平明显升高(P<0.05),小鼠生存时间明显缩短(P<0.05)。IN中低剂量组尤其中剂量组IL-6、TNF-α水平显著降低(P<0.05),各生化指标亦有不同程度的改善(P<0.05),但IN高剂量组较对照组指标比较无统计学意义(P>0.05)。结论炎性细胞因子IL-6、TNF-α与CC的发生密切相关,适当剂量吲哚美辛有显著的逆转CC作用。     

紫杉醇脂质体的体内外抗肿瘤作用研究

[目的]研究注射用紫杉醇脂质体的体外细胞毒作用和体内抗瘤作用及药物毒性。[方法]用MTT法检测紫杉醇脂质体对人肺腺癌细胞株SPC-A1的体外杀伤作用;建立小鼠实体型S180肿瘤模型,共50只,随机分为5组:5%葡萄糖溶液组(空白对照组)、紫杉醇注射液10mg/kg组和15mg/kg组,紫杉醇脂质体10mg/kg组和15mg/kg组,观察各组抑瘤作用和小鼠一般状态的变化,并检测肝功能和骨髓像改变。[结果]紫杉醇脂质体对体外培养的人肺腺癌细胞株SPC-A1在浓度为2.5ng/ml、5.0ng/ml和10.0ng/ml时,其抑制率分别为39.1%、51.9%和55.8%。体内给予紫杉醇脂质体10mg/(kg·d),15mg/(kg·d)3d,对小鼠S180实体型的抑瘤率分别为31.12%和45.29%,与同样剂量紫杉醇注射液组比较无显著性差异;给药后动物行为和小鼠体重变化率较紫杉醇注射液组接近对照组;骨髓抑制程度亦低于同剂量紫杉醇注射液组。[结论]相同给药剂量下,紫杉醇脂质体的体内外抗肿瘤活性与紫杉醇注射液相接近,但药物毒副反应明显降低。     

5-Fu不同应用方式对大白鼠骨髓影响的观察

目的观察不同方式静脉注射5-Fu对wistar大白鼠白细胞、血小板下降的影响变化,为制定适合我国患者的5-Fu给药方案提供依据.方法本文将大白鼠分为三大组,每大组分为三小组,应用恒速静脉输液泵恒速静滴5-Fu,三大组剂量分别为10mg/(kg·d)、20mg/(kg·d)、30mg/(kg·d),每大组分为三小组,静滴时间分别为10分钟、2小时、4小时,连续用5天,处死大白鼠检测白细胞和血小板情况.结果第一组无论时间的长短均未发现骨髓抑制,第二组短时间用药骨髓抑制明显,第三组无论时间长短均有骨髓抑制,并且时间越短抑制越明显.结论 5-Fu随着剂量的增加出现骨髓抑制并且加重,随着用药时间的延长骨髓抑制减轻,最佳的剂量为20mg/(kg·d),最佳的用药时间应不小于4小时.     

四环素诱导Balb/c小鼠肝脏脂肪代谢相关基因表达谱的变化

背景与目的利用小鼠毒理基因芯片观察四环素对Balb/c小鼠肝脏脂肪代谢相关基因表达的影响。材料与方法设计200mg/(kg.d)和50mg/(kg.d)剂量条件下包含3个时相点的四环素致小鼠肝脏损伤动物模型,提取小鼠肝脏RNA样本,利用小鼠毒理基因芯片进行杂交实验。结果综合各组基因表达谱分析发现与脂肪代谢相关的差异表达基因28个,涉及肝内脂肪合成、分解代谢、转运等多方面,对这些基因的功能和相互关系进行了初步分析和探讨。结论四环素作用于Balb/c小鼠肝脏后引起脂肪代谢相关多个基因显著改变,为深入探讨四环素肝脏毒性分子机制提供了线索。     

刺参酸性黏多糖对5-FU治疗小鼠肝癌的减毒增效作用

目的探讨刺参酸性黏多糖(stichopus japonicus acid mucopolysaccharide,SJAMP)联合5-FU对肝癌小鼠肿瘤生长及免疫功能的影响,了解其对化疗药的减毒增效作用。方法将60只小鼠随机分为正常对照组(生理盐水)、空白对照组(生理盐水)、5-FU组〔5-FU 20 mg/(kg·d)〕、SJAMP组〔SLAMP 25 mg/(kg·d)〕、SJAMP+低5-FU组〔SLAMP 25 mg/(kg·d)和5-FU 10 mg/(kg·d)〕和SJAMP+高5-FU组〔SLAMP 25 mg/(kg·d)和5-FU20mg/(kg·d)〕。除正常对照组外其他各组均于右腋皮下接种H22(Hepatocarcinoma22)细胞。接种后第2天开始给药,连续给药12d后处死小鼠,计算抑瘤率、胸腺指数和脾脏指数,ELISA检测血清TNF-α和IL-2含量,中性红法检测腹腔巨嗜细胞吞噬功能,CCK-8法测定脾脏淋巴细胞增殖能力,MTT法测NK细胞杀伤功能,流式细胞术检测小鼠外周血T细胞亚群。结果各干预组小鼠肿瘤生长明显受到抑制,SJAMP+高5-FU组抑瘤率(62.73%)高于5-FU组(55.53%),P=1.000。SJAMP组和SJAMP+低5-FU组小鼠脾脏指数显著高于其他组,P值均<0.05。SJAMP组和SJAMP+低5-FU组小鼠胸腺指数分别为(2.19±1.18)和(2.13±1.00)mg/g,高于5-FU组的(1.14±0.53)mg/g,P值分别为0.026和0.048;也高于SJAMP+高5-FU组的(1.07±0.49)mg/g,P值分别为0.011和0.020。各药物干预组TNF-α较空白对照组均降低,P值均<0.001。和空白对照组(33.27±6.13)相比,5-FU组(23.52±3.31)血清IL-2水平明显降低,P<0.001;SJAMP组(39.56±2.39)血清IL-2水平显著提高,P=0.001。与5-FU组相比,SJAMP组和联合用药组IL-2明显提高,P值均<0.001。SJAMP组和SJAMP+低5-FU组腹腔巨嗜细胞吞噬中性红能力显著高于正常对照组、空白对照组、5-FU组和SJAMP+高5-FU组,P值均<0.001;SJAMP+高5-FU组与5-FU组相比明显提高,P=0.012。SJAMP组和SJAMP+低5-FU组脾脏淋巴细胞增殖能力显著高于正常对照组(P值均<0.001)、空白对照组(P值均<0.001)、5-FU组(P值均<0.001)和SJAMP+高5-FU组(P值分别为0.005和0.011);SJAMP+高5-FU组与5-FU组相比明显提高,P=0.005。SJAMP组和SJAMP+低5-FU组NK细胞杀伤能力高于5-FU组,P值分别为0.002和0.030。空白对照组和5-FU组CD3+CD4+与CD3+CD8+细胞比值低于正常对照组(P值均<0.001)、SJAMP组(P值分别为0.001和<0.001)和SJAMP+低5-FU组(P值分别为0.003和0.024),SJAMP+高5-FU组高于5-FU组(P=0.329)。结论 SJAMP能够增强5-FU对肿瘤的抑制作用,减少5-FU对小鼠免疫功能的损伤。     

以结直肠癌常用化疗药建立肝损伤动物模型的分析与探讨

目的:使用结直肠癌常用化疗药物（氟尿嘧啶、奥沙利铂、伊立替康）分别处理荷瘤小鼠,观察小鼠肝损伤的病理分型及严重程度。方法:C57/BL 小鼠接种Lewis 肺癌细胞建立皮下移植瘤模型,建模后第10天分别腹腔注射L-OHP（8mg/kg,qd×3d）、5-FU（25mg/kg,qd×5d）及CPT-11(20mg/kg,qd×5d),于给药结束后第2天处死动物,制作肝脏病理切片观察肝脏损伤情况。结果:成功建立了Lewis 肺癌细胞C57/BL 小鼠皮下移植瘤模型;各组肝脏组织学未见脂肪变性、纤维化及炎性浸润,偶见肝细胞水肿。结论:使用氟尿嘧啶、奥沙利铂、伊立替康分别腹腔注射处理荷瘤小鼠后,短时间内未造成荷瘤小鼠肝脏组织的明显损伤。     

The medically important dematiaceous fungi and their identification

Dematiaceous fungi include a large group of organisms that are darkly pigmented (dark brown, olivaceous, or black). In most cases the pigment is melanin, and specifically, dihydroxynaphthalene melanin. The diseases produced include chromoblastomycosis, eumycotic mycetoma, and phaeohyphomycosis. Phaeohyphomycosis is a new classification for a diverse group of previously known entities grouped together on the basis of finding dematiaceous hyphal and/or yeast-like forms in tissue; tissue involvement may be superficial, cutaneous and corneal, subcutaneous, or systemic. Identification of these fungi is based mostly upon morphology. Important structures include annellides (Phaeoannellomyces, Exophiala), phialides (Phialophora, Wangiella), adelophialides (Phialemonium without collarettes, Lecythophora with collarettes), differentiation of conidiophores (Xylohypha versus Cladosporium) and conidial hilum, septation and germination (Bipolaris, Drechslera, Exserohilum). Useful laboratory tests include the 12% gelatin test (controversial), nitrate assimilation (W. dermatitidis is negative, most other species are positive), and determination of temperature maxima (especially 37 degrees C for E. jeanselmei, 40 degrees C for W. dermatitidis and B. spicifera, 42 degrees C for X. bantiana, and 45 degrees C for Dactylaria constricta var. gallopava and Scedosporium inflatum).     

Orale Langzeitbehandlung von Onychomykosen mit Ketoconazol

Zusammenfassung: An der Studie zur Wirksamkeit und Anwendungssicherheit von Ketoconazol nahmen 27 Männer im Alter von 20 bis 80 (Median: 57) Jahre, davon 18 mit Onychomykosen und 9 als KontroUen bei den Laborwertbestimmungen, teil. Während des ersten Behandlungsmonats erhielten je 9 Patienten 200 mg und 400 mg Ketoconazol täglich. Danach wurden beide Gruppen 6 Monate mit 200 mg/d weiterbehandelt. Die klinische Beurteilung sowie hämatologische, biochemische und Plasmaspiegeluntersu-chungen erfolgten mindestens monafich, mykologische Untersuchungen wurden vor Aufnahme und bei Beendigung der Therapie vorgenommen. Erne letzte klinische Unter-suchung erfolgte 1 Jahr nach Beginn der Studie. Nach 7 Monaten Behandlung wurden 23 von 30 Nägeln mit “gebessert” bis “stark gebessert” beurteilt, nach dem behandlungsfreien Intervall galt dies für 28 von 30 Nägeln. Die Plasmaspiegel waren mit 200 mg/d ausreichend und uber den Behandlungszeit-raum konstant. Dies spricht für gute orale Resorption und Abwesenheit von Enzyminduktion. Die Laborwerte zeigten im Vergleich zu den Kontrollen und den Werten vor Behandlung keine signifikanten Abweichungen, so daß myelo-, nephro- und hepatotoxische Wirkungen von 400 bzw. 200 mg/d ausgeschlossen werden können. Der Lipidhaushalt wurde nicht beeinfluat und es trat unter Therapie als Folge der Ketoconazolwirkung lediglich Lanosterin im Serum auf. Nach Beendigung der Therapie ging der Lanosteringehalt schnell zurück. Damit erweist sich Ketoconazol in den angewandten Dosen als ein gut verträgliches und zur Langzeitbehandlung von Onychomykosen geeignetes Antimykotikum. Summary: Twenty-seven males with a median age of 57 (range: 20 to 80) years took part in this study on the efficacy and safety of ketoconazole. Eighteen men suffered from onychomycosis; nine served as controls in the safety evaluation. During the first month of treatment, nine patients received 200 mg and the nine other 400 mg ketoconazole daily. Then the treatment was uniformly continued with 200 mg/d for 6 months. Clinical evaluation and haematological, biochemical and plasma level investigations were carried out at least at monthly intervals; mycological controls were performed at the start and end of therapy. A final clinical evaluation was carried out one year after the start of the study. After 7 months of treatment, moderate or definite clinical improvement was obtained in 23 out of 30 nails. After 5 more months without antimycotic treatment this was the case in 28 of 30 nails. Plasma levels obtained with 200 mg ketoconazole daily were adequate and constant during the entire treatment period. This indicates a good oral resorption as well as the absence of induction of hepatic enzymes. The laboratory values did not show significant deviations as compared with the controls or with the pretreatment values. This excludes myelo-, nephro- and hepatotoxic effects of 400 and 200 mg ketoconazole daily. The lipid metabolism was not influenced, the only difference was the occurrence of lanosterol in the serum, which is a result of the mechanism of action of ketoconazole. After the medication period the lanosterol levels subsided rapidly. In the applied doses ketoconazole is a well-tolerated and effective drug for the systemic long-term treatment of onychomycosis.     

裘法祖教授生平

Prof.Fazu Qiu,member of the Chinese Communist Party,surgery professor of Tongji Hospital,departed in Tongji Hospital,Wuhan,China,at fourteen to nine a.m,June 14,2008,after a disease.He turns 94 this year.He was the senior academician of the Academia Sinica,the illustrious medical scientist of China,and the Honorary Director of Tongji Medical College,as well as Huazhong University of Science & Technology.     

Dermatomycosis in Dogs

During the routine examination of dogs for cutaneous lesions, 205 dogs were screened for fungi other than dermatophytes. Twenty-two dogs (10.8%) revealed the presence of non-dermatophytic fungi suspicious for representing the etiologic agents of the skin lesions. The fungi isolated were Alternaria sp. (2.9%), Penicillium sp. (2.4%), Aspergillus fumigatus (2.0%), Mucor sp. (1.5%), Cladosporium sp. (1.5%) and Fusarium sp. (0.5%). No dermatophyte was isolated in association with these fungi. The incidence of these infections was found to be greater in warm and humid climate.     

Laboratory Techniques Alternative to In Vivo Experiments for Studying the Liberation, Penetration and Fungicidal Action of Topical Antimycotic Agents in the Skin, Including Ciclopiroxolamine

Summary: Short-term experiments on excised skin (human, pig) gave the following results: 1. In the tissue activity test with direct inoculation (D-TAT) commercial preparations of the non-azole antimycotics ciclopiroxolamine, tolnaftate and naftifine, produced higher inhibitory activity against Trichophyton mentagrophytes (standard strain) in various levels of the horny layer than were produced by the azole antimycotics econazole, miconazole, clotrimazole, oxiconazole and bifonazole. Fast drying solutions of antimycotics invariably gave higher inhibitory activities than creams. In the ultrafiltration tissue activity test (UFT- TAT) against Candida albicans (2 strains), antimycotic agents ranked in order of effectiveness as follows: ciclopiroxolamine – most of the azole antimycotics – bifonazole and naftifine. 2. In tests of fungicidal activity against T. mentagrophytes (2 strains) and Microsporum gypseum (1 strain) the first step was to inoculate the skin surface. After the horny layer had been penetrated by fungal mycelia, antimycotic agents of documented fungicidal potency, chiefly in the form of creams, were applied to the skin surface and left to act for up to 18 hours. The horny layer and epidermis were then scraped off and the concentration of viable fungi was determined. Ciclopiroxolamine cream and lotion produced by far the greatest diminution in viable fungi; creams containing oxiconazole and naftifine were moderately effective and those containing tioconazole and bifonazole produced a relatively small decrease in viable fungi. To avoid erroneous results it is important to homogenize and dilute the skin scrapings; if this is not done certain antimycotics will give misleadingly high fungal killing rates. At this early stage the scatter of results is still wide and minor differences in efficacy cannot as yet be detected with certainty. 3. From the results of various comparative tests it is evident that pig skin can be used as a substitute for human skin in the tests listed under 1. and 2. above. This discovery may make a valuable contribution towards limiting the need for experiments on living animals and trials on human beings. Zusammenfassung: In Kurzzeitversuchen an exzidierter Haut (Mensch, Schwein) wurde gefunden: 1. Im Gewebeaktivitätstest mit direkter Inokulation (D-GAT) wurde mit Handelspräparaten der Nichtazol-Antimykotika Ciclopiroxolamin, Tolnaftat und Naftifin in verschiedenen Hornschichtniveaus eine höhere Hemmaktivität gegenüber Trichophyton mentagrophytes (Standard-Stamm) erzielt als mit solchen der Azol-Antimykotika Econazol, Miconazol, Clotrimazol, Oxiconazol und Bifonazol. Rasch trocknende Lösungen von Antimykotika ergaben durchweg höhere Hemmaktivitäten als Cremes. Im Ultrafiltrations-Gewebeaktivitätstest (UFT-GAT) gegenüber Candida albicans (2 Stämme) ergab sich nach erzielter Wirksamkeit die Rangfolge Ciclopiroxolamine – Mehrzahl der Azolantimykotika – Bifonazol und Naftifin. 2. In Fungizidie-Testen gegenüber T. mentagrophytes (2 Stämme) und Microsporum gypseum (1 Stamm) wurde zunächst die Hautoberfläche inokuliert. Nach Durchdringung der Hornschicht mit Pilzmyzelien wirkten auf die Hautoberfläche bis zu 18 Stunden lang überwiegend Cremes von als fungizid publizierten Antimykotika ein. Während sich in abgeschabter Hornschicht und Epidermis der so bearbeiteten Hautoberflächen mit Ciclopiroxolamin-Creme und -Lotion die weitaus höchste Verminderung lebensfähiger Keime ergab, bewirkten Cremes mit Oxiconazol und Naftifin eine mittlere und solche mit Tioconazol und Bifonazol eine relativ niedrige Keimeliminierung. Zur Vermeidung von fehlerhaften Ergebuissen mußten Homogenisierung und Verdünnung der Hautschabsel erfolgen, anderenfalls bei mehreren Antimykotika eine zu hohe Keimabtötung vorgetäuscht worden wäre. Wegen der vorerst noch hohen Streuung der Ergebnisse können kleinere Wirksamkeitsunterschiede noch nicht sicher erfaßt werden. 3. Nach dem Ergebnis verschiedener Vergleichstests kann in den Testen zu 1. und 2. Schweinehaut als Ersatz für Haut vom Menschen dienen und dürfte damit wesentlich zur Einschränkung von Versuchen am lebenden Tier und von Prüfungen am Menschen beitragen.     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

Antifungal combination therapy in localized candidosis

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed. We have now tested various antifungal combinations in this animal model. Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen. The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare. The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance. A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.     

Les génériques en cancérologie: à molécule identique, médicaments identiques? Les biosimilaires, des super-génériques?

Résumé: Les biosimilaires vont bientôt voir leur apparition en Europe. Comment un laboratoire peut-il aborder le développement de son dossier dAMM? Quelles sont les bases légales et les recommandations officielles? Comment la similarité et/ou le caractère générique peuvent-ils être démontrés? Les règles sont-elles identiques à celles des produits chimiques conventionnels pour lesquels, notamment en cancérologie, il existe des médicaments génériques? Comment faire pour que la sécurité et lefficacité des médicaments biosimilaires soient assurées pour les patients?