Glycaemia,arterial pressure and micro-albuminuria in Type 1 (insulin-dependent) diabetes mellitus

Summary Plasma glucose control and arterial pressure were assessed in 28 Type 1 (insulin-dependent) diabetic patients with different degrees of micro-albuminuria. They were divided into two groups according to their urinary albumin excretion rate: a low micro-albuminuria group (n= 16) with albumin excretion ranging between 12.1 and 28.9 g/min and a high micro-albuminuria group (n= 12) with albumin excretion between 32.4 and 91.3 g/min. The groups were matched for age, sex and duration of diabetes with the same number of normo-albuminuric (2.0–10.4 g/min) diabetic control subjects. Both the low and high micro-albuminuria groups had significantly higher glycosylated haemoglobin levels and mean plasma glucose concentrations during a 24-h profile than their respective normo-albuminuric control subjects. A correlation between glycosylated haemoglobin level and urinary albumin excretion rate was found in the whole study group (r= 0.48; p< 0.001). Arterial pressure (both systolic and diastolic) was significantly higher in the high micro-albuminuria group than in either the control group or the low microalbuminuria group. A significant correlation was found between arterial pressure and albumin excretion rate in the whole study population (r= 0.49; p< 0.001) as well as in the pooled micro-albuminuria groups (r= 0.43; p< 0.05). Multiple regression analysis showed that glycosylated haemoglobin and arterial pressure levels were independently correlated with albumin excretion rates. Diabetic patients with micro-albuminuria of any degree have worse glycaemic control than normo-albuminuric patients. Higher levels of arterial pressure, though often sub-hypertensive, are associated with levels of micro-albuminuria predictive of later development of clinical proteinuria. Thus high plasma glucose and high arterial pressure, or both, characterise those diabetic patients at increased risk of nephropathy. These indices of risk are potentially reversible.     

急性中毒心肌损伤早期检测和肽素与缺血修饰白蛋白的临床价值

目的：探讨急性中毒心肌损伤早期检测和肽素与缺血修饰白蛋白（ IMA）的临床意义。方法将急性中毒3 h内患者255例,根据是否存在心肌损伤分为心肌损伤组160例（其中轻度30例、中度60例、重度70例）和非心肌损伤组95例,另选健康体检者50例作为对照组。比较3组心肌酶、心肌肌钙蛋白 I（ cTnI）、和肽素、IMA 水平。结果心肌损伤组、非心肌损伤组患者和肽素水平明显高于对照组（P＜0．05）,且心肌损伤组明显高于非心肌损伤组（P＜0．05）,重度组高于心肌损伤轻、中度组（P＜0．05）;心肌损伤组IMA水平明显低于对照组和非心肌损伤组（P＜0．05）,重度组低于心肌损伤轻、中度组（P＜0．05）。心肌损伤组、非心肌损伤组、对照组肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、cTnI水平比较,差异均无统计学意义（P＞0．05）。心肌损伤重度组患者cTnI水平明显高于轻、中度组（P＜0．05）,但轻、中度两组间cTnI水平比较无统计学意义（P＞0．05）。心肌损伤轻、中、重度组患者CK、CK-MB比较,差异均无统计学意义（P＞0．05）。心肌损伤组患者和肽素与IMA水平呈负相关（r＝－0．603,P＜0．01）。结论和肽素、IMA水平可在早期反映急性中毒性心肌损伤程度并评估预后转归情况。     

3项指标联合检测对糖尿病及其并发症的意义

目的探讨超敏C反应蛋白(hs-CRP)、同型半胱氨酸(Hcy)、缺血修饰清蛋白(IMA)三者联合检测对糖尿病(DM)及其并发症的意义。方法对健康对照组、单纯糖尿病组、糖尿病合并视网膜病变(DR)组、糖尿病肾病(DN)组、糖尿病合并冠心病(CHD)组的hs-CRP、Hcy和IMA值进行测定,统计分析各组之间三者水平的差异是否有统计学意义。结果单纯糖尿病组、DR组、DN组、CHD组hs-CRP、Hcy、IMA水平均高于健康对照组,差异有统计学意义(t=4.433,P=0.000;t=2.930,P=0.004;t=4.590,P=0.000;t=5.328,P=0.000。t=8.629,P=0.000;t=11.229,P=0.000;t=11.230,P=0.000;t=12.444,P=0.000。t=6.271,P=0.000;t=5.511,P=0.000;t=5.950,P=0.000;t=12.463,P=0.000)。三者水平均以CHD组最高。DN组及CHD组hs-CRP、Hcy和IMA水平与单纯糖尿病组相比,差异均有统计学意义(t=3.130,P=0.002;t=3.640,P=0.000;t=2.102,P=0.039。t=2.505,P=0.014;t=3.598,P=0.001;t=2.821,P=0.006)。DR组Hcy和IMA水平与单纯糖尿病组相比,差异有统计学意义(t=2.082,P=0.041;t=2.613,P=0.011),两组hs-CRP水平差异无统计学意义(t=1.717,P=0.090)。单纯糖尿病组IMA与hs-CRP和Hcy呈正相关(r=0.348,P=0.000;r=0.271,P=0.004);糖尿病并发症组IMA与hs-CRP和Hcy也呈正相关(r=0.294,P=0.002;r=0.257,P=0.007),且hs-CRP与Hcy呈正相关(r=0.210,P=0.010)。结论 hs-CRP、Hcy、IMA与糖尿病及其并发症密切相关,三者联合检测有助于监测和控制糖尿病及并发症的发生和发展。     

Glycolaldehyde and maleyl conjugated human serum albumin as potential macrophage‐targeting carriers for molecular imaging purposes

Maleylated bovine serum albumin is a known ligand for targeting macrophages and has potential as a carrier for molecular imaging purposes. We present a novel synthesis of glycolaldehyde‐conjugated human serum albumin (GA‐HSA) and maleylated human serum albumin (Mal‐HSA). Seventeen modifications of fluorescently tagged GA‐HSA and Mal‐HSA molecules with different degrees of conjugation were prepared. The comparative uptake studies, using 12 of these modifications, were done in vitro on mouse monocytes/macrophages (RAW264.7), and evaluated qualitatively by confocal microscopy and quantitatively by flow cytometry. The GA modifications are taken up by the macrophages approximately 40% better than the maleyl modifications at low concentrations (≤3 μm ), while at higher concentrations it appears that the maleyl modifications are taken up around 25–44% better than the GA‐modified HSA. However, high uptake at low concentrations will be beneficial for in vivo localizing inflammation in areas with low penetration of the probe as in an atherosclerotic plaque. Further, another advantage of GA‐HSA is that GA competes less than the maleyl group for the free reactive amine sites that are to be used for conjugation of metal chelating ligands (e.g. tetraazacyclododecanetetraacetic acid and triazacyclononanetriacetic acid). Metal ions such as Gd³⁺ and Mn²⁺ can be chelated for positive Magnetic Resonance (MR) contrast and positron emitting ions such as ⁶⁴Cu²⁺ and ⁶⁸Ga³⁺ for Positron Emission Tomography (PET) imaging. These are important properties, especially, when considering the MR contrast possibilities owing to the low sensitivity of the technique, and would motivate the use of GA‐HSA before Mal‐HSA. © 2014 The Authors. Contrast Media & Molecular Imaging published by John Wiley & Sons, Ltd.     

棉酚与人血清白蛋白相互作用及其分子模拟研究

摘 要 目的： 探讨棉酚与人血清白蛋白(HSA)的相互作用。方法: 采用荧光光谱方法研究在生理条件下,棉酚与人血清白蛋白（HSA）的相互作用,并采用分子对接软件模拟棉酚与人血清白蛋相互作用。结果:棉酚与HSA的结合常数为2.390 6×10⁵ L·mol^-1 (293K) 和3.576 8×10³ L·mol^-1（303K）, 具有一个结合位点,结合反应的主要作用力为氢键和范德华力,结合位置更接近于人血清白蛋白的酪氨酸残基,分子模拟分析也证实此结果。结论: 棉酚对人血清白蛋白的荧光猝灭机制属于静态荧光猝灭。     

西红康对实验性糖尿病肾病大鼠肾脏结构和功能的影响

目的：考察西红康对实验性糖尿病肾病大鼠肾脏结构和功能的影响。方法32只 Wistar 大鼠（雄性）随机分为模型组、西红康组、糖适平阳性组和正常对照组,每组8只,建立糖尿病肾病大鼠模型,对大鼠进行8周的治疗,检测记录治疗前后大鼠的血糖、体重和尿微量白蛋白,分别采用光学显微镜及透射电镜观察大鼠肾脏的结构变化。结果给药前,各组动物的血糖、体重和尿微量白蛋白中均无统计学差异（P ＞0．05）。给药8周后,血糖水平、体重和尿微量白蛋白指标,阳性组和西红康组相对于模型组均有统计学差异（P ＜0．05）。正常组大鼠肾脏肾小球结构完整,肾脏系膜细胞、滤过膜内皮细胞和足细胞均结构正常,模型组大鼠肾小球体积增大,系膜细胞发生中度增生,毛细血管基底膜结构模糊,内皮细胞胞质局部融合,阳性组和西红康组均能不同程度降低肾小球大小,缓解系膜细胞增生,毛细血管基底膜结构更为清晰,内皮细胞胞质融合程度下降。结论西红康可减轻实验性糖尿病肾病大鼠肾脏病理损害,改善肾脏功能。     

Prognostic significance of the combination of preoperative hemoglobin,albumin, lymphocyte and platelet in patients with gastric carcinoma: a retrospective cohort study

Nutritional and immune status is important to the prognosis of patients with gastric carcinoma (GC). Here, we evaluated the prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) in patients with GC. From January 2005 to December 2011, 1332 patients with GC who underwent gastrectomy were randomly divided into the training (n = 888) and the validation sets (n = 444) by X-tile according to the sample size ratio 2:1. The cut-point of HALP was 56.8 and the patients were subsequently subdivided into HALP < 56.8 and HALP ≥ 56.8 groups in both two sets. Multivariate analysis revealed that gender (p < 0.001, p < 0.001), tumor size (p = 0.003, p = 0.035) and T stage (p < 0.001, p = 0.044) were independently related to HALP both in the training and the validation sets. Kaplan-Meier (p < 0.001, p = 0.003) and Cox regression (p = 0.043, p = 0.042) showed that the prognosis of HALP ≥ 56.8 group was significantly better than that of HALP < 56.8 group both in two sets (p < 0.001, p < 0.001). Nomograms of these two sets based on HALP was more accurate in prognostic prediction than TNM stage alone. Our findings suggested that HALP was closely associated with clinicopathological features and was an independent prognostic factor in GC patients. Nomogram based on HALP could accurately predict the prognosis of GC patients.     

High preoperative serum globulin in rectal cancer treated with neoadjunctive chemoradiation therapy is a risk factor for poor outcome

An elevated serum albumin (ALB) and albumin/globulin ratio (AGR) has been reported to be associated with a favorable prognosis for certain malignancies; however, little is known about the prognostic significance of globulin (GLB) in rectal cancer treated with neoadjuvant chemoradiation therapy (NCRT). The purpose of this study was to evaluate whether GLB analysis could predict the prognosis of patients received NCRT. A retrospective cohort of 293 locally advanced rectal cancer patients receiving NCRT followed by radical surgery was recruited between January 2006 and December 2012 at Fudan University Shanghai Cancer Center. Levels for preoperative GLB and ALB were obtained and used to calculate the AGR. Survival analysis was used to evaluate the predictive value of GLB. X-tile program determined 28.50, 36.20 and 1.20 as optimal cut-off value for GLB, ALB and AGR in terms of survival. Univariate and multivariate analysis revealed that low GLB levels were significantly associated with favorable rectal cancer-specific survival (RCSS) (P < 0.05). Conversely, low ALB levels were associated with a significantly worse RCSS (P = 0.010). Collectively, high preoperative GLB level was a significantly unfavorable factor for rectal cancer patients treated with NCRT. This easily obtained variable may serve as a valuable marker to predict the outcomes of such patient population.     

Hypoalbuminemia: Pathogenesis and Clinical Significance

Hypoalbuminemia is associated with inflammation. Despite being addressed repeatedly in the literature, there is still confusion regarding its pathogenesis and clinical significance. Inflammation increases capillary permeability and escape of serum albumin, leading to expansion of interstitial space and increasing the distribution volume of albumin. The half‐life of albumin has been shown to shorten, decreasing total albumin mass. These 2 factors lead to hypoalbuminemia despite increased fractional synthesis rates in plasma. Hypoalbuminemia, therefore, results from and reflects the inflammatory state, which interferes with adequate responses to events like surgery or chemotherapy, and is associated with poor quality of life and reduced longevity. Increasing or decreasing serum albumin levels are adequate indicators, respectively, of improvement or deterioration of the clinical state. In the interstitium, albumin acts as the main extracellular scavenger, antioxidative agent, and as supplier of amino acids for cell and matrix synthesis. Albumin infusion has not been shown to diminish fluid requirements, infection rates, and mortality in the intensive care unit, which may imply that there is no body deficit or that the quality of albumin “from the shelf” is unsuitable to play scavenging and antioxidative roles. Management of hypoalbuminaemia should be based on correcting the causes of ongoing inflammation rather than infusion of albumin. After the age of 30 years, muscle mass and function slowly decrease, but this loss is accelerated by comorbidity and associated with decreasing serum albumin levels. Nutrition support cannot fully prevent, but slows down, this chain of events, especially when combined with physical exercise.