Antioxidant enzymes and lipoperoxide in blood in uremic children and adolescents

To determine whether oxidant-antioxidant balance is altered in chronic renal failure, antioxidant enzymes and lipid peroxide in peripheral blood cells and lipid peroxide in plasma were measured. Nine children and adolescents maintained on hemodialysis (HD), 9 on continuous ambulatory peritoneal dialysis (CAPD), and 14 controls were studied. Lipid peroxide was assayed fluorimetrically as thiobarbituric acid-reactive substances, superoxide dismutases by radioimmunoassays. Both manganese and copper-zinc superoxide dismutases in lymphocytes and monocytes in the HD and CAPD patients, and manganese superoxide dismutase in polymorphs in the HD patients were higher than in the controls. Copper-zinc superoxide dismutase, glutathione peroxidase, and catalase in erythrocytes were unaltered. The lipid peroxide level in plasma in the dialyzed patients was increased, whereas those in polymorphs and lymphocytes were unaltered. Triglyceride and total cholesterol in plasma in the dialyzed patients were also increased. The plasma lipid peroxide in the patients correlated with the triglyceride and total cholesterol level. This is the first study in which manganese superoxide dismutase is measured in nucleated cells of the patients with chronic renal failure. The present results suggest that increased superoxide dismutases protect against oxidative stress induced by chronic renal failure in nucleated cells but in neither erythrocytes nor plasma.     

高通量血液透析对尿毒症患者营养状况的影响

目的:探讨高通量血液透析对尿毒症患者营养状况的影响。方法:自身对照研究将38例维持性低通量血液透析患者转换为高通量血液透析(HPD),HPD组使用日本旭化成APS-15u高通量透析器6个月,分别采用改良主观全面营养评估(MQSGA)及各项客观营养指标进行相关性分析。结果:经转换为高通量血液透析后主观全面营养评估较使用低通量血液透析有显著性差异;营养相关指标血清白蛋白(ALB)、血红蛋白较前有明显提高,差异有显著性(P<0.05);胆固醇较前相比无明显差异。结论:高通量血液透析能有效改善维持性透析患者的营养状况。     

高通量血液透析对尿毒症患者营养状况的影响

目的：探讨高通量血液透析对尿毒症患者营养状况的影响。方法：自身对照研究将38例维持性低通量血液透析患者转换为高通量血液透析（HPD）,HPD组使用日本旭化成APS-15u高通量透析器6个月,分别采用改良主观全面营养评估（MQSGA）及各项客观营养指标进行相关性分析。结果：经转换为高通量血液透析后主观全面营养评估较使用低通量血液透析有显著性差异;营养相关指标血清白蛋白（ALB）、血红蛋白较前有明显提高,差异有显著性（P〈0.05）;胆固醇较前相比无明显差异。结论：高通量血液透析能有效改善维持性透析患者的营养状况。     

93例糖尿病住院患者的营养状况评价

对糖尿病住院患者入院时进行营养评价,分别对93例30～60岁糖尿病患者入院时做人体测量和生化检查,与正常人群作对照.结果显示,观察组患者的体质量、体质指数、总蛋白、白蛋白、低密度酯蛋白以及三酰甘油的平均值均高于正常组、而高密度脂蛋白低于正常组,差异有显著性意义(p＜0.05).结果表明,采用多项综合指标评价糖尿病患者的...     

终末期糖尿病肾病的血液透析与腹膜透析的比较研究

目的:探讨终末期糖尿病肾病患者接受不同透析方法的临床疗效。方法:40例终末期糖尿病肾病患者,按照透析方式分为血液透析和腹膜透析组,回顾性分析其临床资料。结果:血液透析与腹膜透析在血压控制,血糖,白蛋白、血总蛋白,肌酐、尿素氮水平,甘油三酯以及出血发生率等各项指标有其各自的优劣性,但是均可使患者获益,提高生存率,生存率比较无统计学差异。结论:及时、恰当的选择肾脏替代治疗,并在治疗过程中及时调整,甚或更换方案对终末期糖尿病肾病患者是有益的。     

Inflammatory cytokines and malnutrition as related to risk for cardiovascular disease in hemodialysis patients

Malnutrition and inflammation are associated with end-stage renal disease (ESRD). Interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) powerfully predict death from cardiovascular disease. The aim of our study was to establish an association between markers of inflammation and parameters of malnutrition in patients on hemodialysis. The study population consisted of 42 hemodialysis patients with different parameters of malnutrition. Blood samples were taken after an overnight fast, and plasma lipid profiles (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) were measured by using conventional enzymatic methods. Serum urea and creatinine levels were also measured by routine procedures. Plasma high-sensitivity C-reactive protein level (hs-CRP), TNF-alpha, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Standard Doppler echo examinations were used to determine plaque on carotid arteries, and end-diastolic diameter (EDD) and ejection fraction (EF) were measured by echocardiography. Malnourished patients exhibited significantly greater evidence of cardiovascular disease and carotid plaques. Factor (principal component) analysis indicated 6 latent factors with 67.5% of the variance explained within all investigated parameters. Cluster analysis was used to distinguish the inflammatory markers and the nutritional markers from other parameters and to visualize similarities between variables. In summary, this cross-sectional study in hemodialysis patients found a high prevalence of malnutrition, inflammation, carotid plaques, and cardiovascular disease. Malnourished dialysis patients are more often found with cardiovascular disease and carotid plaques. In addition, these patients have higher levels of inflammatory cytokines, which may partly explain the elevated risk for atherosclerotic vascular disease.     

Inflammation but Not Dietary Macronutrients Insufficiency Associated with the Malnutrition-Inflammation Score in Hemodialysis Population

Malnutrition is associated with increased risk of mortality in hemodialysis patients. And insufficient dietary intake is the common cause for malnutrition. So, in order to survey the dietary intake of hemodialysis patients and study the relationship between the dietary feature and nutritional status, a cross-sectional study was performed. 75 hemodialysis patients from South China participated in the dietary intake survey and nutrition assessment. A three-day diet diary record was used to estimate the major dietary macronutrients. Nutritional status was assessed by malnutrition-inflammation score (MIS) in addition to several related anthropometric measurements. Serum albumin, transferrin, and high-sensitivity C-reactive protein (CRP) were measured. Receiver operating characteristic (ROC) curve analysis was used to quantify the assessing value of independent parameters for nutritional status. The results showed that 48% patients were malnourished according to the MIS. The malnourished patients had a lower body mass index (BMI), fat mass (FM), albumin and a higher level of CRP, compared with normal nourished patients (P < 0.05). However, no significant differences of macronutrients (calories, protein, fat, carbohydrates, etc) were found between the two nutrition groups (P > 0.05). The multivariate regression analysis showed that the major macronutrients had no significant association with MIS (P > 0.05). In conclusion, malnutrition is very common in South China hemodialysis population and these data indicated that inflammation but not dietary macronutrients insufficiency might be the candidate cause for malnutrition in hemodialysis population.     

Oxidative modifications impair albumin quantification

Background

Hypoalbuminemia is a measure of malnutrition, inflammation and a predictor of mortality in uremia. It is controversial whether albumin levels per se are associated with the clinical outcomes in uremic patients. The co-occurrence of hypoalbuminemia and oxidative stress in hemodialysis (HD) patients led us to hypothesize that oxidative modifications of albumin decrease its detection and influence albumin quantification.

Methods

Albumin levels are determined in clinical laboratories mainly by the bromocresol green (BCG) spectrophotometric assay. The detection of serum albumin was investigated in HD patients and in healthy controls using an “albumin-detection index”, defined as the ratio between BCG read-out (albumin-specific) to total albumin. The detection efficacy of albumin was also investigated in vitro, after glycoxidation, HOCl-mediated-oxidation, and metal-catalyzed-oxidation. Oncotic pressure was measured to assess albumin function.

Results

The albumin-detection index of patients was significantly lower compared with controls, correlating negatively with oxidative stress markers (serum advanced oxidation protein products-AOPP and glycoxidized serum albumin) and positively with serum albumin levels. The albumin-detection index was also decreased after in vitro oxidation.

Conclusions

The study shows, both in vivo and in vitro, decreased detection of oxidized albumin by a commonly-used clinical assay, thus providing the molecular link between oxidative stress and hypoalbuminemia. Oxidative stress as reflected by hypoalbuminemia, rather than actual albumin levels, may be related to cardiovascular morbidity outcomes in HD patient.     

Coordinated increase in albumin, fibrinogen, and muscle protein synthesis during hemodialysis: role of cytokines

Serum albumin, fibrinogen levels, and lean body mass are important predictors of outcome in end-stage renal disease (ESRD). We estimated the fractional synthesis rates of albumin (FSR-A), fibrinogen (FSR-F), and muscle protein (FSR-M) in nine ESRD patients and eight controls, using primed constant infusion of l-[ring-(13)C(6)]phenylalanine. Cytokine profile and arteriovenous balance of amino acids were also measured. ESRD patients were studied before (Pre-HD) and during hemodialysis (HD). Plasma IL-6, IL-10, and C-reactive protein increased significantly during HD. Despite a decrease in the delivery of amino acids to the leg, the outflow of the amino acids increased during HD. The net balance of amino acids became more negative during HD, indicating release from the muscle. HD increased leg muscle protein synthesis (45%) and catabolism (108%) but decreased whole body proteolysis (15%). FSR-A during HD (9.7 +/- 0.9%/day) was higher than pre-HD (6.5 +/- 0.9%/day) and controls (5.8 +/- 0.5%/day, P < 0.01). FSR-F increased during HD (19.7 +/- 2.6%/day vs. 11.8 +/- 0.6%/day, P < 0.01), but it was not significantly different from that of controls (14.4 +/- 1.4%/day). FSR-M intradialysis (1.77 +/- 0.19%/day) was higher than pre-HD (1.21 +/- 0.25%/day) and controls (1.30 +/- 0.32%/day, P < 0.001). Pre-HD FSR-A, FSR-F, and FSR-M values were comparable to those of controls. There was a significant and positive correlation between plasma IL-6 and the FSRs. Thus, in ESRD patients without metabolic acidosis, the fractional synthesis rates of albumin, fibrinogen, and muscle protein are not decreased pre-HD. However, HD increases the synthesis of albumin, fibrinogen, and muscle protein. The coordinated increase in the FSRs is facilitated by constant delivery of amino acids derived from the muscle catabolism and intradialytic increase in IL-6.     

开同对维持性血液透析患者营养及脂质代谢的影响

目的：研究复方α-酮酸对维持性血液透析（MHD）患者营养及脂质代谢的影响。方法：将40例MHD患者随机分为两组：（1）实验组（n=20）,予常规蛋白饮食,并服用复方α-酮酸12片／d;（2）对照组（n=20）,子常规蛋白饮食,不服用复方α-酮酸。分别于治疗前、治疗后3个月后测定各项血生化指标及人体测量学指标。结果：经3个月治疗后,实验组血白蛋白、前白蛋白较前明显升高（P〈0．01）,总胆固醇和甘油三酯明显下降（P〈0．01）,血红蛋白无明显变化（P〉0．05）;对照组血红蛋白、血白蛋白、前白蛋白及血脂无明显变化;实验组及对照组治疗前后体重指数、肱三头肌皮褶厚度、上臂肌围无明显变化（P〉0．05）。结论：复方α-酮酸可有效改善维持性血液透析患者营养状况以及脂质代谢,但长期使用该疗法的疗效和安全性有待于进一步的研究。     

Repeated immune activation with low-dose lipopolysaccharide attenuates the severity of Huntington's disease in R6/2 transgenic mice

Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in the huntingtin gene. Previously, therapeutic approaches using anti-inflammatory agents were reportedly not effective for preventing HD progression. Since whether immune responses contribute to the onset of HD is not entirely understood, we herein investigated the role of immune activation in HD using the R6/2 transgenic (Tg) HD model mouse. IL12 production and the expression of costimulatory molecules (e.g. CD86 and CD40) on innate immune cells (DCs and macrophages) were diminished in the disease stage of R6/2 Tg mice. Moreover, the number of adaptive T cells (CD4⁺ and CD8⁺ T cells) and the frequency of effector memory phenotype CD4⁺ T cells were decreased in these mice. These results suggest that the severity of HD is closely related to an impaired immune system and might be reversed by activation of the immune system. Since lipopolysaccharide (LPS), a potent TLR4 agonist, activates immune cells, we evaluated the effect of immune activation on the pathogenesis of HD using LPS. The repeated immune activation with low-dose LPS significantly recovered the impaired immune status back to normal levels and attenuated both severe weight loss and the increased clasping phenotype found in the disease stage of R6/2 Tg mice, consequently resulting in prolonged survival. Taken together, these results strongly indicate that immune activation has beneficial influences on alleviating HD pathology and could provide new therapeutic strategies for HD.     

Diet-dependent effects of insulin infusion on the hepatic lipoprotein receptors and the key enzymes of bile acid synthesis in the hamster.

The effects of an induced hyperinsulinemia on both the cholesterol and bile acid metabolisms were analyzed in the hamster. The role of dietary sucrose as modulator of these effects was evaluated by feeding the animals with two semi-synthetic diets containing a low (SD, 20%) and a high (LD, 62.5%) sucrose proportion. Hamsters fed under basal nutritional conditions (chow diet, CD) were also used. LD enabled the consequences of an insulin infusion on cholesterol gallstone formation to be evaluated. Subcutaneous osmotic pumps were implanted in all the animals and delivered either 3 IU/day of insulin (insulin groups: CDI, SDI, LDI) or saline (control groups: CDC, SDC, LDC). Several parameters bound to lipid metabolism were measured. The plasma cholesterol concentration remained constant in all the insulin treated groups compared to the controls. Phospholipid and triglyceride concentrations decreased in both the plasma and liver in the CDI and SDI groups. A lower SR-BI mass (around 50%) was found in the liver of CDI and SDI hamsters with concomitant higher hydroxy-methyl-glutaryl coenzyme A reductase activity. The LDL-receptor mass and cholesterol 7alpha-hydroxylase activity in the LDI group were both decreased (-47%, -71% respectively). No variations in the cholesterol gallstone incidence were observed. In conclusion, chronic insulin infusion in growing hamsters induced similar effects on cholesterol metabolism in the CD and SD groups but different ones, between diets containing a low (SD) and a high (LD) sucrose proportion. The distribution of triglycerides and phospholipids in the plasma, liver and bile was also affected by the insulin infusion.     

乙型肝炎病毒不同基因分型与淋巴细胞亚群分布、肝功能及脂代谢的关系

目的:探讨乙型肝炎病毒(HBV)不同基因分型与淋巴细胞亚群分布、肝功能及脂代谢的关系。方法:选择2016年10月-2017年12月在我院治疗的HBV患者130例,将患者进行HBV基因分型检查,根据不同基因分型将患者分为B型组(n=59)和C型组(n=71),采用实时荧光PCR法检测血清HBV-DNA载量,采用ADVIA2400全自动生化分析仪测定患者丙氨酸转氨酶(ALT)、白蛋白(ALB)、总胆红素(Tbil)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,采用美国ACL-TOP700血凝仪检测凝血酶原时间(PT)。采用流式细胞仪测定不同基因分型患者CD3~+、CD4~+、CD8~+及CD4~+/CD8~+水平。结果:两组患者HBV-DNA载量、PT比较差异无统计学意义(P0.05);B型组患者ALT、ALB、TbiL水平均低于C型组(P0.05)。B型组患者CD3~+、CD4~+、CD4~+/CD8~+水平均高于C型组,CD8~+水平低于C型组(P0.05)。两组患者TC、TG、HDL-C和LDL-C水平比较差异无统计学意义(P0.05)。结论:不同基因分型对HBV患者病毒复制能力及脂代谢无明显影响,但C型HBV对患者免疫功能及肝功能损伤更严重。     

Non-fasting serum triglyceride concentration and mortality from coronary heart disease and any cause in middle aged Norwegian women.

OBJECTIVE--To study the association between non-fasting serum triglyceride concentrations and mortality in women from coronary and cardiovascular disease and all causes. DESIGN--Follow up by ambulatory teams of men and women who underwent cardiovascular screening for a mean of 14.6 years. SETTING--National health screening service in Norway. SUBJECTS--25,058 men and 24,535 women aged 35-49 years. MAIN OUTCOME MEASURE--Predictive value of non-fasting serum triglyceride concentrations. RESULTS--At initial screening total serum cholesterol concentration, serum triglyceride concentration, blood pressure, height, and weight were measured, and self reported information about smoking habits, physical activity, and time since last meal were recorded. During subsequent follow up 108 women died from coronary heart disease, 238 from cardiovascular diseases, and 931 from all causes. In women mortality increased steadily with increasing triglyceride concentration for all three causes of death. With the proportional hazards model and adjustment for age, systolic blood pressure, total cholesterol concentration, time since last meal, and number of cigarettes a day the relative risk between triglyceride concentration > or = 3.5 mmol/l and < 1.5 mmol/l was 4.7 (95% confidence interval 2.5 to 8.9) for deaths from coronary heart disease, 3.0 (1.9 to 4.8) for deaths from cardiovascular disease, 2.3 (1.8 to 2.9) for total deaths in all women. CONCLUSIONS--A raised non-fasting concentration of triglycerides is an independent risk factor for mortality from coronary heart disease, cardiovascular disease, and any cause mortality among middle aged Norwegian women in contrast to what is seen in men.     

HDL proteome in hemodialysis patients: a quantitative nanoflow liquid chromatography-tandem mass spectrometry approach

Aside from a decrease in the high-density lipoprotein (HDL) cholesterol levels, qualitative abnormalities of HDL can contribute to an increase in cardiovascular (CV) risk in end-stage renal disease (ESRD) patients undergoing chronic hemodialysis (HD). Dysfunctional HDL leads to an alteration of reverse cholesterol transport and the antioxidant and anti-inflammatory properties of HDL. In this study, a quantitative proteomics approach, based on iTRAQ labeling and nanoflow liquid chromatography mass spectrometry analysis, was used to generate detailed data on HDL-associated proteins. The HDL composition was compared between seven chronic HD patients and a pool of seven healthy controls. To confirm the proteomics results, specific biochemical assays were then performed in triplicate in the 14 samples as well as 46 sex-matched independent chronic HD patients and healthy volunteers. Of the 122 proteins identified in the HDL fraction, 40 were differentially expressed between the healthy volunteers and the HD patients. These proteins are involved in many HDL functions, including lipid metabolism, the acute inflammatory response, complement activation, the regulation of lipoprotein oxidation, and metal cation homeostasis. Among the identified proteins, apolipoprotein C-II and apolipoprotein C-III were significantly increased in the HDL fraction of HD patients whereas serotransferrin was decreased. In this study, we identified new markers of potential relevance to the pathways linked to HDL dysfunction in HD. Proteomic analysis of the HDL fraction provides an efficient method to identify new and uncharacterized candidate biomarkers of CV risk in HD patients.     

尿毒症维持性血液透析患者血清CRP与营养状态及感染的相关性

目的:探讨尿毒症维持性血液透析患者的血清C-反应蛋白(CRP)与营养状态及感染的相关关系。方法:按照是否发生感染将2013年2月-2015年8月我院收治的238例尿毒症维持性血液透析患者分为感染组(118例)和非感染组(120例),对两组患者的血清CRP、营养状态相关指标进行比较,并分析CRP水平与营养状态及感染的相关性。结果:感染组的体质量指数(BMI)、白蛋白、前白蛋白、转铁蛋白、血红蛋白水平低于非感染组,重组人促红细胞生成素、血清CRP水平高于非感染组,肱三头肌皮褶厚度低于非感染组,差异均有统计学意义(P0.05)。经Pearson积矩相关分析,血清CRP与BMI、白蛋白、前白蛋白、转铁蛋白、血红蛋白呈负相关关系(r=-0.81、-0.93、-0.85、-0.79、-0.91),差异有统计学意义(P0.05),血清CRP与肱三头肌皮褶厚度(TSF)呈负相关关系(r=-0.76,P0.05),与重组人促红细胞生成素呈正相关关系(r=0.89,P0.05)。结论:尿毒症维持性血液透析患者的血清CRP水平可作为评估患者营养状态及感染的重要指标,具有重要的参考价值。     

The structure and function of oxidized albumin in hemodialysis patients: Its role in elevated oxidative stress via neutrophil burst

Oxidized albumin is a reliable marker of oxidative stress in hemodialysis (HD) patients. However, oxidized albumin in vivo and its possible clinical significance has been rarely investigated. In the present study, the qualitative modification of albumin in HD patients (n = 20) was examined and their results were compared with healthy age-matched controls (n = 10). The increase in plasma protein carbonyl levels in HD patients was largely due to an increase in oxidized albumin. Human serum albumin (HSA) of HD patients, HSA of HD patients (HD-HSA) and normal subjects (Normal-HSA) were purified on a blue Sepharose CL-6B column. Spectroscopic analysis confirmed that the HD-HSA samples contained higher levels of carbonyls than Normal-HSA. An HPLC analysis also suggested that the state of the purified HSA used throughout the experiments accurately reflects the redox state of albumin in blood. HD-HSA was found to have a decreased the antioxidant activity, and was able to trigger the oxidative burst of human neutrophils, compared to Normal-HSA. HD-HSA was conformationally altered, with its hydrophobic regions more exposed and to have a negative charge. In binding experiments, HD-HSA showed impaired Site II-ligand binding capabilities. Collectively, the oxidation of plasma proteins, especially HSA, might enhance oxidative stress in HD patients.     

Morphometric variables related to metabolic profile in captive chimpanzees (Pan troglodytes)

Obesity is a risk factor for several diseases including type 2 diabetes and cardiovascular disease. The aim of this study was to compare the relationships of waist circumference and body weight with circulating markers of metabolic, cardiovascular, and hepatic function in chimpanzees (Pan troglodytes). After a 12-h fast, blood was collected from 39 adult captive chimpanzees for measurement of serum glucose, BUN, creatinine, albumin, cholesterol, ALT, AST, ALP, total and direct bilirubin, triglyceride, and insulin, and waist circumference and body weight were measured. Waist circumference was positively correlated with systolic and diastolic blood pressure, glucose, insulin resistance as estimated by the homeostatic model assessment method, and albumin in female chimpanzees and with triglyceride in female and male chimpanzees. Body weight was correlated significantly with systolic and diastolic blood pressure in female chimpanzees and triglyceride in male chimpanzees. Male chimpanzees were heavier and had lower diastolic blood pressure, greater creatinine, albumin, AST, ALP, total bilirubin, and direct bilirubin values than did female chimpanzees. The relationships between waist circumference and blood pressure and triglyceride are consistent with those reported in humans and other primate species. In conclusion, our study is the first work to demonstrate a relationship between waist circumference and metabolic risk factors in chimpanzees. Results demonstrated that waist circumference was associated with more metabolic risk factors than was body weight, particularly in female chimpanzees.