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.     

Corticotroph axis sensitivity after exercise: comparison between elite athletes and sedentary subjects

Strenuous exercise activates the hypothalamic-pituitary-adrenal (HPA) axis. Several reports showed that physical training is associated with a decreased efficiency of the feedback control of HPA axis. The aims of the present study were: 1) to evaluate the differences in the mechanical, hormonal, and lactate responses to a high-intensity isokinetic exercise among different groups of competitive athletes (CA, no.=20) of power and endurance disciplines and sedentary controls (SED, no.=10); 2) to determine the effects of the training status on the HPA axis responsiveness following exercise, as indirectly evaluated by the rates of ACTH, cortisol, and DHEA recovery after exercise. CA and SED fulfilled eight sets of twenty concentric contractions of the knee extensors at 180 degrees/sec angular velocity throughout a constant range of motion (100 degrees). There was a rest period of 30 sec between each set and a 3-min rest period between the two legs. Before, immediately after the isokinetic exercise and at different times in the subsequent 120 min of recovery, blood and saliva were sampled to determine plasma ACTH, salivary cortisol, serum DHEA, and serum lactate concentrations. CA showed a higher cortisol response to exercise than SED, whereas no differences were found in the responses of ACTH, DHEA and lactate. In the athlete group the exercise-induced increases of ACTH, cortisol, and lactate were higher in power athletes with respect to endurance athletes. No differences were observed between athletes and SED in the rates of hormonal recovery after exercise: this finding does not support the concept that a reduced feedback control of HPA axis can represent a feature of trained individuals.     

The Accelerating Access Initiative: experience with a multinational workplace programme in Africa

Problem

A multinational company with operations in several African countries was committed to offer antiretroviral treatment to its employees and their dependants.

Approach

The Accelerating Access Initiative (AAI), an initiative of six pharmaceutical companies and five United Nations’ agencies, offered the possibility of obtaining brand antiretroviral drugs (ARVs) at 10% of the commercial price. PharmAccess, a foundation aimed at removing barriers to AIDS treatment in Africa, helped to establish an HIV policy and treatment guidelines, and a workplace programme was rolled out from September 2001.

Local setting

Private sector employers in Africa are keen to take more responsibility in HIV prevention and AIDS care. An important hurdle for African employers remains the price and availability of ARVs.

Relevant changes

The programme encountered various hurdles, among them the need for multiple contracts with multiple companies, complex importation procedures, taxes levied on ARVs, lack of support from pharmaceutical companies in importation and transportation, slow delivery of the drugs, lack of institutional memory in pharmaceutical companies and government policies excluding the company from access to ARVs under the AAI.

Lessons learned

The launch of the AAI enabled this multinational company to offer access to ARVs to its employees and dependants. The private sector should have access to these discounted drugs under the AAI. A network of local AAI offices should be created to assist in logistics of drugs ordering, purchase and clearance. No taxes should be levied on ARVs.     

IGOB131, a novel seed extract of the West African plant Irvingia gabonensis, significantly reduces body weight and improves metabolic parameters in overweight humans in a randomized double-blind placebo controlled investigation

Background  

A recent in vitro study indicates that IGOB131, a novel seed extract of the traditional West African food plant Irvingia gabonensis, favorably impacts adipogenesis through a variety of critical metabolic pathways including PPAR gamma, leptin, adiponectin, and glycerol-3 phosphate dehydrogenase. This study was therefore aimed at evaluating the effects of IGOB131, an extract of Irvingia gabonensis, on body weight and associated metabolic parameters in overweight human volunteers.     

A prognostic index relating 24-hour ambulatory blood pressure to cardiac events in ischemic cardiomyopathy following defibrillator implantation

Background: We assessed the role of left ventricular ejection fraction and of ambulatory blood pressure monitoring (ABPM) to predict cardiac death and heart failure in patients with defibrillator fulfilling MADIT II criteria. ABPM variables assessed included: mean 24 hours diastolic and systolic blood pressure, mean 24 hours heart rate, and pulse pressure.
Methods: We studied 105 consecutive patients (age 67 ± 11), all with a defibrillator and ejection fraction ≤ 30%).
Results: At 1-year follow-up, there were 29 events (25%), three cardiac deaths, and 26 hospitalizations for heart failure. Age, creatinine, mean 24 hours diastolic blood pressure, and mean 24 hours systolic blood pressure (but not ejection fraction) were associated with events. A prognostic index (PI) was built by age and ABPM variables, according to the formula (120 – age) + (mean 24 hours diastolic blood pressure + mean 24 hours systolic blood pressure). Receiver operating characteristic curves showed the best cutoff for PI = 220 (sensitivity 81%, specificity 71%, positive predictive value 56%, negative predictive value 88%). Cox regression analysis confirmed the significant association between lower PI (< 220) and clinical events (HR 4.8, 95% CI 1.8–12.3, P = 0.0001 for PI). Overall, 12% of patients with high PI values (≥ 220 n = 71) had clinical events at 12-month follow-up, compared with 61% of patients with low PI (< 220 n = 34) (P < 0.0001).
Conclusion: The PI built by mean 24 hours diastolic and systolic blood pressure and age could be a simple method to stratify risk of cardiac death and acute heart failure in MADIT II patients, in whom ejection fraction, uniformly depressed, is not predictive.     

Produits sanguins labiles provenant de donneurs immunisés dans le système HLA. À propos d'un cas d'œdème pulmonaire lésionnel

A case of transfusion-related acute lung injury (TRALI) due to HLA antibodies present in one unit of packed red blood cells led us to discuss the screening of HLA antibodies for female donors having been pregnant, and the use of labile blood products.