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。     

猪胸腰段脊髓火器贯通伤后p53基因的早期表达

目的:建立家猪胸腰段脊髓火器贯通伤模型和改良Allen's打击伤后全瘫模型,观察伤后促凋亡基因p53基因的早期表达。方法:实验于2005-05/08在解放军第一七五医院实验室完成。取健康雄性家猪20只,单纯随机分为3组:①火器伤组:9只,在全麻状态下制作胸腰段(L1～L2)脊髓火器伤模型,分为伤后1,3,6h3个时间处死。②打击伤组:9只,L1节段脊髓行改良Allen’s打击,致伤力为500g·cm,处死时间同前。③空白对照组:2只,只麻醉,不造模,伤后6h处死。伤后不同时间点(伤后1,3,6h)和不同节段(伤点、近伤点、中伤点及远伤点)取材,采用SP法进行P53蛋白免疫组化染色,用TJTY-300型全自动图像分析仪测量P53免疫组织化学染色阳性物质吸光度。结果:经补充后20只猪进入结果分析。①脊髓损伤后3h打击伤组伤点,火器伤组近伤段脊髓P53蛋白的表达高于空白对照组(P<0.001),随着时间推移,打击伤组和火器伤组P53蛋白的表达呈升高趋势(P<0.001),且火器伤组要高于打击伤组(P<0.0001)。②在脊髓损伤后6h,打击伤组仅在伤点和近伤段P53蛋白的表达高于空白对照组(5.57±0.82,3.21±0.43,P<0.05),而火器伤组近伤段、中伤段及远段伤均高于空白对照组(6.46±0.66,4.27±0.39,1.16±0.17,P<0.05)。结论:①细胞凋亡基因p53在脊髓损伤中的表达有一定的时空性,在脊髓损伤后3h出现P53蛋白表达量的增加。②脊髓火器伤的波及范围较打击伤更为广泛。     

Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients

HIV infection is characterized by an enhanced oxidant burden and a systemic deficiency of the tripeptide glutathione (GSH), a major antioxidant. The semi-essential amino acid cysteine is the main source of the free sulfhydryl group of GSH and limits its synthesis. Therefore, different strategies to supplement cysteine supply have been suggested to increase glutathione levels in HIV-infected individuals. The aim of this study was to evaluate the effect of oral supplementation with two different cysteine-rich whey protein formulas on plasma GSH levels and parameters of oxidative stress and immune status in HIV-infected patients. In a prospective double blind clinical trial, 30 patients (25 male, 5 female; mean age (+/- SD) 42 +/- 9.8 years) with stable HIV infection (221 +/- 102 CD4 + lymphocytes L-1) were randomized to a supplemental diet with a daily dose of 45 g whey proteins of either Protectamin (Fresenius Kabi, Bad Hamburg, Germany) or Immunocal (Immunotec, Vandreuil, Canada) for two weeks. Plasma concentrations of total, reduced and oxidized GSH, superoxide anion (O2-) release by blood mononuclear cells, plasma levels of TNF-alpha and interleukins 2 and 12 were quantified with standard methods at baseline and after therapy. Pre-therapy, plasma GSH levels (Protectamin: 1.92 +/- 0.6 microM; Immunocal: 1.98 +/- 0.9 microM) were less than normal (2.64 +/- 0.7 microM, P = 0.03). Following two weeks of oral supplementation with whey proteins, plasma GSH levels increased in the Protectamin group by 44 +/- 56% (2.79 +/- 1.2 microM, P = 0.004) while the difference in the Immunocal group did not reach significance (+ 24.5 +/- 59%, 2.51 +/- 1.48 microM, P = 0.43). Spontaneous O2- release by blood mononuclear cells was stable (20.1 +/- 14.2 vs. 22.6 +/- 16.1 nmol h-1 10-6 cells, P = 0.52) whereas PMA-induced O2- release decreased in the Protectamin group (53.7 +/- 19 vs. 39.8 +/- 18 nmol h-1 10-6 cells, P = 0.04). Plasma concentrations of TNF-alpha and interleukins 2 and 12 (P > 0.08, all comparisons) as well as routine clinical parameters remained unchanged. Therapy was well tolerated. In glutathione-deficient patients with advanced HIV-infection, short-term oral supplementation with whey proteins increases plasma glutathione levels. A long-term clinical trial is clearly warranted to see if this "biochemical efficacy" of whey proteins translates into a more favourable course of the disease.     

Hair growth effects of oral administration of finasteride, a steroid 5 alpha-reductase inhibitor, alone and in combination with topical minoxidil in the balding stumptail macaque.

A 5 alpha-reductase inhibitor, finasteride, was administered orally at 0.5 mg/day, alone or in combination with topical 2% minoxidil, for 20 weeks to determine the effects on scalp hair growth in balding adult male stumptail macaque monkeys. A 7-day dose-finding study showed that both 0.5- and 2.0-mg doses of the drug produced a similar diminution in serum dihydrotestosterone (DHT) in male stumptails. Hair growth was evaluated by shaving and weighing scalp hair at baseline and at 4-week intervals during treatment to obtain cumulative delta hair weight (sum of the 4-week changes in hair weight from baseline) for the 20-week study. The activity of the 5 alpha-reductase enzyme was assessed by RIA of serum testosterone (T) and DHT at 4-week intervals. The combination of finasteride and minoxidil generated significant augmentation of hair weight (additive effect) compared to either drug alone. Finasteride increased hair weight in four of five monkeys. When the data of the one nonresponsive monkey were excluded, finasteride elicited a significant elevation in hair weight compared to topical vehicle alone. Minoxidil also evoked a significant increase in hair weight compared to vehicle alone. Serum T was unchanged, whereas serum DHT was significantly depressed in monkeys that received either finasteride or the combination of finasteride and minoxidil. These data suggest that inhibition of the conversion of T to DHT by this 5 alpha-reductase inhibitor reverses the balding process and enhances hair regrowth by topical minoxidil in the male balding stumptail macaque.     

Correlation between Rotator Cuff Tears and Repeated Subacromial Steroid Injections: A Case-Controlled Study

INTRODUCTION

Concern exists regarding potential damage to the rotator cuff from repeated corticosteroid injections into the subacromial space.

PATIENTS AND METHODS

In this retrospective, case-controlled study, 230 consecutive patients presenting to three orthopaedic units with subacromial impingement and investigated as an end-point with magnetic resonance imaging (MRI) of the shoulder were divided into groups having received less than three or three or more subacromial injections of corticosteroids.

RESULTS

With no significant difference in age and sex distribution, analysis by MRI showed no significant difference between the two groups in the incidence of rotator cuff tear (P < 1.0).

CONCLUSIONS

This suggests that corticosteroid use in patients with subacromial impingement should not be considered a causative factor in rotator cuff tears.     

MR spectroscopy in patients with intracranial meningiomas

With magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), we tried to get more pre-operative information in patients with suspicious meningioma concerning the histologic diagnosis especially regarding WHO Grades I and II meningiomas. Apart from the known spectra and metabolites such as choline, creatine and N-acetyl-aspartate (NAA), recent publications have shown that lactate is often found in necrotic tumor tissue. Within a 2 year period, 39 patients with an intracranial meningioma were studied with MRS. In 62.5% of histologic atypical meningiomas (WHO Grade II), a lactate peak could be demonstrated in the pre-operative MRS. Interestingly, also patients with multiple meningiomas show different spectra of their tumors.     

Forearm and leg amino acid metabolism in the basal state and during combined insulin and amino acid stimulation after a 3‐day fast

Aim: Fasting is characterized by a progressive loss of protein, but data on protein kinetics are unclear and few have studied the effects of re‐feeding. The present study was designed to test the hypothesis that a combined infusion of insulin and amino acids after fasting would induce compensatory increases in protein synthesis and reductions in protein breakdown at the whole body level and in muscle. Methods: We included 10 healthy male volunteers and studied them twice: (1) in the post‐absorptive state and (2) after 72 h of fasting. Amino acid kinetics was measured using labelled phenylalanine and tyrosine, whole body energy expenditure was assessed and urea nitrogen synthesis rates were calculated. Results: After fasting we observed an increase in arterial blood concentration of branched chain amino acids and a decrease in gluconeogenic amino acids (P < 0.05). Isotopically determined whole body, forearm and leg phenylalanine fluxes were unaltered apart from a 30% decrease in phenylalanine‐to‐tyrosine conversion (2.0 vs. 1.4 μmol kg^?1 h^?1, P < 0.01). During infusion of insulin and amino acids, amino acid concentrations increased. Conclusion: Our data indicate that after a 72‐h fast basal and insulin/amino acid‐stimulated regional phenylalanine fluxes in leg and forearm muscle are unaltered. During fasting concentrations of gluconeogenic amino acids decrease and hepatic and/or renal phenylalanine‐to‐tyrosine conversion decreases. Thus, as opposed to glucose and lipid metabolism, fasting does not induce insulin resistance as regards amino acid metabolism.     

Circulating Free Fatty Acids do not Contribute to the Acute Systemic Inflammatory Response. An Experimental Study in Porcine Endotoxaemia

Abstract: Intensive insulin therapy, aiming for strict normoglycaemia, is associated with increased survival in critically ill patients. Insulin therapy concomitantly reduces plasma‐free fatty acids. Recent studies indicate that free fatty acids mediate inflammation. In addition to plasma glucose and free fatty acid‐lowering effects, insulin also has anti‐inflammatory properties. This study was designed to study the pro‐inflammatory effects of two free fatty acid concentrations during acute endotoxaemia and controlled comparable levels of plasma glucose and insulin. Twenty pigs were anaesthetized and mechanically ventilated. Pigs were randomized to two different, constant Intralipid^® infusion rates, throughout observation. All pigs were administered continuous intravenous infusion of endotoxin and subjected to controlled levels of p‐glucose (4.5 mmol/l) and insulin by use of a hyperinsulinaemic euglycaemic clamp. Changes in circulating tumour necrosis factor‐α (TNF‐α), interleukin (IL)‐6, leucocytes, insulin, glucose, free fatty acids, triglycerides, albumin, blood gases, temperature, and, haemodynamic function were monitored. Immediately following killing, biopsies were taken from heart and kidney. Biopsies were analysed for protein content of TNF‐α, IL‐6, IL‐8 and IL‐10. Sustained elevated and significantly different plasma levels of free fatty acids were demonstrated between groups (mean free fatty acid concentrations, 1.62 mM versus 0.58 mM, p < 0.0002). Endotoxaemia induced a steep increase in plasma TNF‐α, IL‐6 and leucocytes, however, without differences between the low‐ and high‐free fatty acid groups. Cytokine content in heart and kidney tissue was not modified by free fatty acids. Compared with the response obtained at lower free fatty acid levels, high free fatty acid levels did not exacerbate the inflammatory response to acute endotoxaemia. Our results do not support the role of free fatty acids as a significant pro‐inflammatory mediator.