Papilloma and carcinoma production in DMBA-initiated, onion oil-promoted mouse skin

Groups of 20 females Ha/ICR mice were initiated with 25 micrograms 7,12-dimethylbenz[a]anthracene (DMBA) and promoted one week later with topical treatments three times per week of 5 micrograms phorbol myristate acetate (PMA) and/or onion oil or garlic oil. Promotion was continued for 49 weeks in most experiments. Promotion was continued for 60 weeks in the experiment that evaluated the effect of time intervals between PMA and garlic oil. All experiments were conducted with 0.2 ml acetone solutions of agents. Onion oil, but not garlic oil, was a weak promoter in mouse skin. A 1-mg dose produced five papillomas in three mice and one carcinoma in 330 days (18 survivors). The 10-mg dose was more effective; it produced cumulative yields of 56 papillomas in 14 mice and 7 carcinomas in 4 mice in 345 days (14 survivors). Onion oil is neither an initiator nor a whole carcinogen. The effects of intervals between PMA and a 1-mg dose of onion or garlic oil were determined. These intervals were -2 hrs, -1 hr, -0.5 hr, +0.5 hr, +1 hr, and +2 hrs with respect to time of PMA application. Maximal inhibition of papillomas by onion oil was observed at the +0.5-hr interval and was similar to that previously reported. Garlic oil is not a promoter. It inhibited papillomas at the +0.5-hr, +1.0-hr, and +2.0-hr intervals but did not appear to affect carcinoma production.     

Clinical relaxation: Current controversy

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -     

Relationships Among Alcohol Use, Hyperarousal, and Marital Abuse and Violence in Vietnam Veterans

Alcohol use (frequency and quantity) and the hyperarousal feature of PTSD were examined in relation to male-perpetrated marital abuse and violence using data from 376 couples who participated in the National Vietnam Veterans Readjustment Study. Veteran's self-reported hyperarousal was significantly associated with partner's report of physical violence and psychological abuse toward her. Differential relationships were found between veteran's self-reported drinking frequency and drinking quantity and the outcomes; of the two components, only the average quantity consumed per occasion was independently related to husband-to-wife violence. Moreover, a complex interaction emerged between hyperarousal and the two dimensions of alcohol consumption in predicting violence, with the relationship between hyperarousal and violence varying as a function of both drinking frequency and drinking quantity.     

低血糖指数膳食改善超重老年糖尿病患者氧化应激水平

目的:观察低血糖指数的膳食对2型糖尿病患者氧化应激状态的影响。方法:2004-10/11在上海市静安区二个社区卫生服务中心招募受试者,经医生明确诊断为2型糖尿病、病程超过6个月,体质量指数≥24kg/m2的老年糖尿病志愿者43名,受试者对试验知情同意。采用随机交叉试验随机分配至低血糖指数饮食组和高血糖指数饮食组,每种膳食分别连续使用4周,间隔洗脱期4周,比较试验前后患者超氧化物歧化酶、脂质过氧化产物丙二醛和谷胱甘肽过氧化物酶含量的变化。结果:受试者依从性好,除1人因试验期间发现肿瘤而退出试验,42名志愿者按设计要求完成试验。膳食干预后低血糖指数饮食组和高血糖指数饮食组的超氧化物歧化酶活力分别升高了15.68%和21.33%,丙二醛水平分别下降23.94%和21.55%,谷胱甘肽过氧化物酶活力分别升高了15.74%和17.09%;干预后低血糖指数饮食组丙二醛下降水平与高血糖指数饮食组比较差异有显著性意义(P<0.05),而超氧化物歧化酶和谷胱甘肽过氧化物酶活性两组间差异无显著性意义(P>0.05)。结论:在控制总能量的基础上给予平衡膳食能够改善其氧化应激水平,采用低血糖指数食物有助于氧化应激水平的改善。     

机械力学对体外骨髓间充质干细胞的影响

目的:分析力学刺激体外骨髓间充质干细胞所产生增殖分化等生物学效应的影响及其力化学信号转导途径。资料来源:因特网上检索PubMed数据库中2000-01/2006-06期间有关力学刺激对骨髓干细胞作用效应进展的英文文章,检索词“stem cel1,marrow mesenchymal stem cells,mechanical stimulation,stress”,同时检索CNKI中国知网医学文献数据库2000-01/2006-06期间的相关文章,检索词为“干细胞、骨髓间充质干细胞、机械刺激、应力”。资料选择:对资料进行筛选,选取相关文章查找全文。纳入标准:①骨髓间充质干细胞相关生物学特性。②体外细胞加载的应力分类及相应力学装置的特点。③应力对细胞影响的研究。④能获取文章的全文。排除标准:①较陈旧的文献。②重复研究。资料提炼:共收集关于86篇体外骨髓干细胞及力学干预的相关文献。其中30篇符合纳入标准。资料综合:①骨髓干细胞具有高度增殖及多向分化能力,可通过体外培养、干预作为细胞组织工程的理想种子细胞。②力学刺激是体外调节细胞生物学效应的重要途径,其中力学分类有:流体切应力、静止压应力、张应力、离心力以及单个细胞的吸吮力等,介绍各种力以及相应的力学装置的特点。③骨髓干细胞加载各种应力干预后产生的生物学效应,以及细胞应力学刺激的机制、信号转导途径。结论:力学刺激可影响骨髓间充质干细胞生物学特性,在适当的力学刺激条件下,促进细胞的增殖与分化,为骨组织工程提供新的技术手段,同时也为临床应用牵拉成骨的骨再生过程提供理论依据。     

Fibroblast growth factor 2 decreases bleomycin‐induced pulmonary fibrosis and inhibits fibroblast collagen production and myofibroblast differentiation

Fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of pulmonary fibrosis. Mice lacking FGF2 have increased mortality and impaired epithelial recovery after bleomycin exposure, supporting a protective or reparative function following lung injury. To determine whether FGF2 overexpression reduces bleomycin‐induced injury, we developed an inducible genetic system to express FGF2 in type II pneumocytes. Double‐transgenic (DTG) mice with doxycycline‐inducible overexpression of human FGF2 (SPC‐rtTA;TRE‐hFGF2) or single‐transgenic controls were administered intratracheal bleomycin and fed doxycycline chow, starting at either day 0 or day 7. In addition, wild‐type mice received intratracheal or intravenous recombinant FGF2, starting at the time of bleomycin treatment. Compared to controls, doxycycline‐induced DTG mice had decreased pulmonary fibrosis 21 days after bleomycin, as assessed by gene expression and histology. This beneficial effect was seen when FGF2 overexpression was induced at day 0 or day 7 after bleomycin. FGF2 overexpression did not alter epithelial gene expression, bronchoalveolar lavage cellularity or total protein. In vitro studies using primary mouse and human lung fibroblasts showed that FGF2 strongly inhibited baseline and TGFβ1‐induced expression of alpha smooth muscle actin (αSMA), collagen, and connective tissue growth factor. While FGF2 did not suppress phosphorylation of Smad2 or Smad‐dependent gene expression, FGF2 inhibited TGFβ1‐induced stress fiber formation and serum response factor‐dependent gene expression. FGF2 inhibition of stress fiber formation and αSMA requires FGF receptor 1 (FGFR1) and downstream MEK/ERK, but not AKT signaling. In summary, overexpression of FGF2 protects against bleomycin‐induced pulmonary fibrosis in vivo and reverses TGFβ1‐induced collagen and αSMA expression and stress fiber formation in lung fibroblasts in vitro, without affecting either inflammation or epithelial gene expression. Our results suggest that in the lung, FGF2 is antifibrotic in part through decreased collagen expression and fibroblast to myofibroblast differentiation. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Effects of rosuvastatin on 3-nitrotyrosine and aortic stiffness in hypercholesterolemia

Background and aimsEarly atherosclerosis is characterized by reduced large artery distensibility, paralleled by an increased peroxynitrite formation and nitration of tyrosine in proteins. The aim of the present study was to investigate the short-term effect of cholesterol lowering with rosuvastatin on 3-nitrotyrosine (3-NT), a marker of peroxynitrite-mediated oxidative stress, and on arterial stiffness.Methods and results71 outpatients with primary hypercholesterolemia were recruited for this randomized open-label intervention study; 35 patients were assigned to 4-week rosuvastatin therapy (10 mg daily) with a low-fat diet, and 36 patients to a low-fat diet only. Within the cohort of 71 hypercholesterolemic patients, there was a significant correlation between cholesterol levels, 3-NT and aortic pulse wave velocity (aPWV), that is a reliable measure of aortic stiffness. Among those patients who received rosuvastatin, significant reductions in plasma cholesterol, 3-NT and aPWV were observed. Reductions in both aPWV and 3-NT levels correlated significantly with the decrease in plasma cholesterol. Reduction of plasma cholesterol was the only independent predictor for reduced arterial stiffness following rosuvastatin therapy.ConclusionCholesterol reduction achieved following short-term rosuvastatin therapy is associated with a decrease in peroxynitrite-mediated oxidative stress and an improvement in large artery distensibility; reduction in arterial stiffness is directly attributable to rosuvastatin-induced cholesterol lowering and not to reduction of plasma 3-NT levels.