Correlation of oxidative status with BMI and lung function in COPD

OBJECTIVES: The imbalance in oxidative status together with nutrition depletion and low body weight play a vital role in the pathogenesis and severity of chronic obstructive pulmonary disease (COPD). The study was undertaken to ascertain if a relationship existed between oxidative status and BMI in COPD. In addition, association of oxidative status and BMI with lung function of the disease was also examined. MATERIALS AND METHODS: In 202 COPD patients and 136 healthy controls plasma lipid peroxidation (LPO), reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT) activities, BMI and FEV(1)% predicted were looked for interactions. RESULTS: The patients had increased LPO (p=0.006) and decreased antioxidants (GSH, p=0.005; GPx, p=0.035 and CAT, p=0.008, respectively). Of note are the correlations of oxidative stress markers with BMI and FEV(1)% predicted in the patients. LPO inversely and GSH, GPx, and CAT positively correlated with both BMI (p=0.007, p<0.001, p=0.045 and p=0.009, respectively), and FEV(1)% of predicted (LPO, p=0.001; GSH, p<0.001; GPx, p=0.043 and CAT, p<0.001) in the patients. Further, a positive correlation existed between BMI and FEV(1)% predicted (p=0.016) in COPD. CONCLUSION: The intimate relationship of oxidative status with BMI and lung function, and the direct correlation between BMI and FEV(1) may potentiate severity of the disease.     

The effect of prestorage irradiation on posttransfusion red cell survival

Transfusion-associated graft-versus-host disease (TA-GVHD) may occur whenever immunologically competent allogeneic lymphocytes are transfused to an immunocompromised recipient. Irradiation of blood components eliminates the risk of TA-GVHD but may damage the cellular elements in the transfused component, particularly if the cells are stored for prolonged periods in the irradiated state. To study the effect of irradiation on long-term storage of red cells, AS-1 red cells from eight normal subjects were prepared on two occasions. On one occasion, the units were stored as standard AS-1 red cells for 42 days at 4 degrees C; on the other, they were exposed to 3000 cGy radiation within 4 hours of collection and then were stored as AS-1 red cells for 42 days at 4 degrees C. The donations were at least 12 weeks apart. Irradiated units demonstrated significant elevations in poststorage plasma hemoglobin (Hb) (623 +/- 206 vs. 429 +/- 194 g/dL [6230 +/- 2060 vs. 4290 +/- 1940 g/L], p less than 0.02) and plasma potassium (78 +/- 4 vs. 43 +/- 9 mEq/L [78 +/- 4 vs. 43 +/- 9 mmol/L], p less than 0.01) and significant decreases in red cell ATP (1.9 +/- 0.2 vs. 2.1 +/- 0.3 microM/g Hb, p less than 0.04) and 24-hour posttransfusion red cell recovery (68.5 vs. 78.4%, p less than 0.02), as compared to nonirradiated units. It can be concluded that irradiation with 3000 cGy damages red cells and that long-term storage in the irradiated state may enhance this damage. Red cells should not be stored for 42 days after irradiation with 3000 cGy.     

Stapled Hemorrhoidopexy Compared With Conventional Hemorrhoidectomy: Systematic Review of Randomized,Controlled Trials

PURPOSE This study was designed to determine whether conventional hemorrhoidectomy or stapled hemorrhoidopexy is superior for the management of hemorrhoids.METHODS A systematic review of all randomized trials comparing conventional hemorrhoidectomy with stapled hemorrhoidopexy was performed. MEDLINE, EMBASE, and Cochrane Library databases were searched using the terms hemorrhoid* or haemorrhoid* and stapl*. A list of clinical outcomes was extracted. Meta-analysis was calculated if possible.RESULTS Fifteen trials recruiting 1,077 patients were included. Follow-up ranged from 6 weeks to 37 months. Qualitative analysis showed that stapled hemorrhoidopexy is less painful compared with hemorrhoidectomy. Stapled hemorrhoidopexy has a shorter inpatient stay (weighted mean difference, –1.02 days; 95 percent confidence interval, –1.47 to –0.57; P = 0.0001), operative time (weighted mean difference, –12.82 minutes; 95 percent confidence interval, –22.61 to –3.04; P = 0.01), and return to normal activity (standardized mean difference, –4.03 days; 95 percent confidence interval, –6.95 to –1.10; P = 0.007). Studies in a day-case setting do not prove that stapled hemorrhoidopexy is more feasible than conventional hemorrhoidectomy. Stapled hemorrhoidopexy has a higher recurrence rate (odds ratio, 3.64; 95 percent confidence interval, 1.40–9.47; P = 0.008) at a minimum follow-up of six months.CONCLUSIONS Although stapled hemorrhoidopexy is widely used, the data available on long-term outcomes is limited. The variability in case selection and reported end points are difficulties in interpreting results. Stapled hemorrhoidopexy has unique potential complications and is a less effective cure compared with hemorrhoidectomy. With this understanding, it may be offered to patients seeking a less painful alternative to conventional surgery. Hemorrhoidectomy remains the gold standard of treatment.Reprints are not available.     

复合富血小板血浆的酶处理异种骨修复兔桡骨缺损

目的:自源性的富血小板血浆可促进骨组织及软组织的修复,又不存在疾病传播及免疫排斥的可能。实验拟验证应用复合富血小板血浆的酶处理异种骨修复节段性骨缺损的可行性。方法:实验于2006-07/12在解放军昆明总医院实验动物中心完成。①实验分组:选用新西兰大耳白兔20只,体质量2.0～2.5kg,共40只前肢,随机分为复合酶组,单纯酶组,脱蛋白骨组,空白组。每组共10个标本。②实验方法:制作富血小板血浆及酶处理的异种骨并制备桡骨中段15mm的节段性骨缺损模型,将上述骨材料植入兔桡骨缺损处,其中复合酶组:植入复合富血小板血浆的酶处理异种骨;单纯酶组:植入酶处理异种骨;脱蛋白骨组:植入部分脱蛋白骨;空白组:不植入任何材料。③实验评估:分别于术后4,8,12周取材,X线片及苏木精-伊红染色分别观察骨缺损区的新骨形成情况。同时对各组骨密度进行测定。结果:纳入新西兰大耳白兔20只,均进入结果分析,所有手术无术后感染,无动物死亡,植入骨无脱落。①所有动物麻醉苏醒后均恢复进食,2周伤口愈合,未出现感染及渗液等。富血小板血浆中的血小板含量均为全血的4倍以上。②在同一时间点,酶处理后异种骨与部分脱蛋白骨在成骨能力方面差异无显著性意义,而复合富血小板血浆的酶处理异种骨在8周时骨缺损部分修复;12周时完全修复。空白组骨缺损未修复。③8,12周时复合酶组骨密度较单纯酶组、脱蛋白骨组高,差异有显著性意义(P<0.05);单纯酶组与脱蛋白骨组比较无明显差异(P>0.05)。结论:经酶处理后异种骨可用于节段性骨缺损的修复,复合富血小板血浆后有明显加速骨愈合的作用。     

Synthesis and characterization of scVEGF‐PEG‐[68Ga]NOTA and scVEGF‐PEG‐[68Ga]DOTA PET tracers

Vascular endothelial growth factor (VEGF) signaling via vascular endothelial growth factor receptor 2 (VEGFR‐2) on tumor endothelial cells is a critical driver of tumor angiogenesis. Novel anti‐angiogenic drugs target VEGF/VEGFR‐2 signaling and induce changes in VEGFR‐2 prevalence. To monitor VEGFR‐2 prevalence in the course of treatment, we are evaluating ⁶⁸Ga positron emission tomography imaging agents based on macrocyclic chelators, site‐specifically conjugated via polyethylene glycol (PEG) linkers to engineered VEGFR‐2 ligand, single‐chain (sc) VEGF. The ⁶⁸Ga‐labeling was performed at room temperature with NOTA (2,2′,2′′‐(1,4,7‐triazonane‐1,4,7‐triyl) triacetic acid) conjugates or at 90 °C by using either conventional or microwave heating with NOTA and DOTA (2,2′,2′′,2′′′‐(1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetrayl) tetraacetic acid) conjugates. The fastest (~2 min) and the highest incorporation (>90%) of ⁶⁸Ga into conjugate that resulted in the highest specific radioactivity (~400 MBq/nmol) was obtained with microwave heating of the conjugates. The bioactivity of the NOTA‐ and DOTA‐containing tracers was validated in 3‐D tissue culture model of 293/KDR cells engineered to express high levels of VEGFR‐2. The NOTA‐containing tracer also displayed a rapid accumulation (~ 20 s after intravenous injection) to steady‐state level in xenograft tumor models. A combination of high specific radioactivity and maintenance of functional activity suggests that scVEGF‐PEG‐[⁶⁸ Ga]NOTA and scVEGF‐PEG‐[⁶⁸ Ga]DOTA might be promising tracers for monitoring VEGFR‐2 prevalence and should be further explored. Copyright © 2011 John Wiley & Sons, Ltd.     

Pharmacophore-based 3D-QSAR of HIF-1 inhibitors

(Aryloxyamino)benzoic acids and nicotinic/isonicotinic acids represent an important new class of small molecules that inhibit the activation of Hypoxia-Inducible Factor (HIF)-1. In order to understand the factors affecting inhibitory potency of HIF-1 inhibitors, 3 dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed. Since no receptor structure are available, the pharmacophore-based alignment was used for comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models gave reasonable statistics (CoMFA: q² = 0.564, r²=0.945; CoMSIA: q² = 0.575, r²=0.929). Both CoMFA and CoMSIA results indicate that the steric interaction is a major factor, while CoMSIA suggests importance of hydrogen bonding. These findings about steric and H-bonding effects can be useful to design new inhibitors. Equally contributed in this work.