Serum sCD163 levels are associated with type 2 diabetes mellitus and are influenced by coffee and wine consumption: results of the Di@bet.es study.

OBJECTIVE: Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. RESEARCH DESIGN AND METHODS: This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. RESULTS: sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P<0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46-2,97); P for trend <0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively). CONCLUSIONS: High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes.

Serum correlates of the placebo effect in irritable bowel syndrome.

BACKGROUND In diseases defined primarily by the subjective nature of patient self-report, placebo effects can overwhelm the capacity of randomized controlled trials to detect medication-placebo differences. Moreover, it is unclear whether such placebo effects represent genuine psychobiological phenomena or just shifts in selective attention. Knowledge of predictors of the placebo response could improve the design of clinical trials and the delivery of personalized medical care. METHODS In patients with irritable bowel syndrome (IBS), a subset of our previous study that were randomized to placebo treatment (sham acupuncture) or no-treatment group (waitlist), we tested an enriched panel of 10 serum biomarkers at the enrolment and the 3rd week of intervention, using a multiplex electrochemiluminescent immunoassay. KEY RESULTS More pronounced changes overtime in serum levels of osteoprotegerin (OPG) have been found in patients who received placebo treatment compared with the waitlist group (P = 0.039). Moreover, serum levels of OPG at baseline were found to be higher (P = 0.0167) in patients who subsequently achieved adequate relief (AR) of their IBS symptoms, independently of their treatment group. Besides, serum levels of TNF-related weak inducer of apoptosis (TWEAK) at baseline were also higher (P = 0.0144) in patients who reported AR and in particular in those who received the placebo treatment. CONCLUSIONS & INFERENCES These two measurable biological parameters associated with placebo, namely serum OPG and TWEAK, provide a proof of principle for discovering putative molecular signatures of placebo response in IBS and perhaps in other illnesses with patient self-reported outcomes.

Biomarkers and health-related quality of life in end-stage renal disease: a systematic review.

BACKGROUND AND OBJECTIVES: Health-related quality of life (HRQOL) predicts mortality in ESRD, yet adoption of HRQOL monitoring is not widespread, and regulatory authorities remain predominantly concerned with monitoring traditional biologic parameters. To assist with future efforts to adopt HRQOL monitoring while acknowledging the importance of biomarkers, this study sought to establish which domains of HRQOL are most affected by ESRD and to measure the strength of evidence linking common biomarkers to HRQOL in ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A systematic review was performed to identify studies that measured HRQOL in ESRD. Data were abstracted according to a conceptual model regarding the measurement of HRQOL differences, and HRQOL data were converted to weighted mean effect sizes and correlation coefficients. RESULTS: The impact of ESRD was largest in the Short Form 36 domains of physical functioning (e.g., role-physical, vitality) and smallest in mental functioning (e.g., mental health, role-emotional). Dialysis adequacy, as measured by Kt/V, was a poor correlate for Short Form 36 scores. Similarly, mineral metabolism (e.g., calcium x phosphorous, parathyroid hormone) and inflammatory (e.g., C-reactive protein, TNF) biomarkers had small effect sizes and correlations with HRQOL. In contrast, hematocrit demonstrated small to moderate relationships with mental and physical HRQOL, and nutritional biomarkers (e.g., albumin, creatinine, body mass index) demonstrated moderate to large relationships. CONCLUSIONS: HRQOL in ESRD is most affected in the physical domains, and nutritional biomarkers are most closely associated with these domains. In contrast, Kt/V, mineral metabolism indices, and inflammatory markers are poor HRQOL correlates.

The effect of QuYuHuaTanTongLuo Decoction on the non-alcoholic steatohepatitis.

UNLABELLED: Non-alcoholic steatohepatitis (NASH) is the most common cause of cryptogenic cirrhosis, is becoming more prevalent in China. However, there is as yet no clearly established therapy for reversing fatty liver. Our aim is to explore the effect of traditional Chinese herbs QuYuHuaTanTongLuo Decoction (QYHTTLD) on non-alcoholic steatohepatitis. Sixty-nine non-alcoholic steatohepatitis patients were randomly divided into two groups. One group of 35 patients were treated by QYHTTLD, another group of 34 patients were treated by Ursodeoxycholic acid (UDCA). The TNF-alpha, IL-8, MDA level, SOD activity and liver function, as well as B ultrasonic image were detected before and after being treated. The results showed: after 6 months treatment, MBI of the treatment group was obviously decreased (p<0.05). The levels of TC, TG and LDL-C were significantly decreased whereas the level of HDL-C increased (p<0.01, p<0.05, p<0.05, and p<0.05, respectively) in the treatment group, the levels of TC, TG, LDL-C and HDL-C had no significant difference in the control group (p>0.05). The levels of TNF-alpha, IL-8 and MDA were significantly decreased whereas SOD activity was significantly increased (p<0.01, p<0.05, p<0.01, and p<0.01, respectively) in the treatment group, the level of MDA was significantly decreased in the control group (p<0.05). B ultrasonic images were ameliorated in different degree (p<0.01 and p<0.01, respectively). Both QYHTTLD and UDCA had the effect in improving the scores of symptoms and signs of patients, however, the difference value of the scores in treatment group were significantly higher than that in control group after being treated for 6 months (p<0.05). CONCLUSION: QYHTTLD is effective for treating non-alcoholic steatohepatitis, and its effect seems to relate with the ways of QYHTTL down-regulating inflammation cytokine IL-8 level and relieving lipid peroxidation of liver.

Seasonal changes of proapoptotic soluble Fas ligand level in allergic rhinitis combined with asthma.

The function of apoptosis is to eliminate unnecessary or dangerous cells. The balance between production and death is important in the control of cell numbers within physiological ranges. Cells involved in allergic reactions may have altered apoptosis. The aim of this study was to examine the seasonal changes of programmed cell death in children with pollen allergy. We measured serum levels of soluble Fas (sFas) and soluble Fas ligand (sFasL), and examined whether there was any correlation between soluble apoptosis markers and development of asthma and or rhinitis in children with pollen allergy. We examined two groups of patients with ragweed pollen allergy. The first group consisted of 17 children with 'rhinitis only'. The second group consisted of 16 children with 'asthma + rhinitis'. For seasonal analysis we pooled the two groups and termed this the 'ragweed sensitive' group (n = 33, 5-18 yr, 25 boys, eight girls). Measurements (sFas and sFasL) were taken during the ragweed pollen allergy season, while control measurements were performed during the symptom-free period. There was no difference in sFas levels measured during and after [1941 +/- 68, 1963 +/- 83 pg/ml (mean+/-s.e.m, respectively)] the pollen season in the 'ragweed sensitive' group. The sFasL level showed seasonal change, which was significantly higher (p = 0.0086) in the symptomatic period compared to the symptom-free state (99 +/- 13 and 53 +/- 16 pg/ml, respectively). There was a difference between the 'rhinitis only' and the 'asthma + rhinitis' groups in the measured parameters of apoptosis. Children having allergic rhinitis combined with asthma had a significantly (p = 0.03) higher sFas level in the symptom-free state than the 'rhinitis only' group did (2115 +/- 156 and 1820 +/- 52 pg/ml, respectively). During the allergic symptom state the sFasL level of the 'asthma + rhinitis' group was significantly higher (p = 0.025) than that of the 'rhinitis only' group (125 +/- 20 and 75 +/- 14 pg/ml, respectively). In conclusion, the increased level of sFasL during the pollen season may signal its role in the pathogenesis of allergic airway diseases. There was no seasonal change in sFas levels in the examined ragweed allergic group, however in the symptomatic period we observed a diminished level of antiapoptotic factor (sFas) and an elevated level of proapoptotic factor (sFasL) if there was a combined disease with pollen allergic asthma. We suggest that there is a deviation in the apoptotic reaction in children that may increase the seasonal allergic inflammation.

Reduced cytokines release and myocardial damage in coronary artery bypass patients due to L-arginine cardioplegia supplementation.

BACKGROUND: Recently, L-arginine has been added to cardioplegia to limit myocardial ischemic damage. The mechanism of action is related to the production of nitric oxide, with vasodilatation and reduction of endothelial dysfunction. Our prospective randomized study on coronary artery bypass patients investigates the effect of L-arginine on myocardial stress as expressed by myocardial cytokines release and myocardial ischemia in terms of troponin T concentration. METHODS: Coronary artery surgery patients were randomly assigned to receive 7.5 g L-arginine in 500 mL of cardioplegic solution (group A). Group B was used as control. Cold blood 4:1 anterograde and retrograde cardioplegia with warm induction was administered. Blood samples were collected from the retrograde coronary sinus catheter to determine interleukin-2 receptor, interleukin-6, and tumor necrosis factor levels. Serum samples at different time points were also analyzed to measure myocardial ischemia markers. Hemodynamic and echocardiographic evaluations were obtained perioperatively. RESULTS: Sixty-five patients were enrolled (group A, treated with L-arginine, n = 33; group B, control, n = 32). Wedge pressure and intensive care unit stay were significantly reduced in group A (p = 0.023 and p = 0.03, respectively). Cytokines levels were lower in group A, with a significance for interleukin-6 (p = 0.026); troponin T was reduced in treated patients (0.33 versus 0.57 ng/mL at 18 hours: p = 0.009). CONCLUSIONS: Coronary artery surgery patients benefit from L-arginine cardioplegia supplementation in terms of reduced inflammatory reaction, limitation of myocardial ischemia, and better hemodynamic performance. Moreover, a clinical advantage is evident in terms of a shorter intensive care unit stay in patients treated with L-arginine.

[Effect of Astragalus injection on plasma levels of apoptosis-related factors in aged patients with chronic heart failure].

OBJECTIVE: To investigate the effect of Astragalus injection (AI) on plasma levels of apoptosis-related factors in aged patients with chronic heart failure (CHF). METHODS: Seventy-two CHF patients were randomly divided into the AI group (36 cases) treated with AI and the control group (36 cases) treated with conventional treatment. Plasma levels of soluble Fas (sFas), soluble Fas ligand (sFasL), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assays (ELISA) with monoclonal anti-human antibodies. Besides, New York Heart Association (NYHA) grading was assessed according to improved symptoms and left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were assessed by echocardiogram after 4 weeks of treatment. RESULTS: After 4 weeks of treatment, NYHA grading was markedly improved in the two groups, but it was significantly better in AI group than that in the control group (P < 0.05). As compared with the control group, sFas, sFasL, TNF-alpha and IL-6 in the AI group were obviously lower, the difference between the two groups and between before and after treatment were significant (P < 0.05 or P < 0.01). Moreover, in AI group, LVESV and LVEDV decreased, LVEF increased, which was significantly different than that before treatment (P < 0.05), respectively. CONCLUSION: AI could lower plasma levels of apoptosis-related factors, and is one of the effective drugs in improving cardiac function in the aged patients with CHF.

[Effects of high dose glucose-insulin-potassium infusion on myocardial injury and serum sFas/ sFasL concentration in acute myocardial infarction].

OBJECTIVE: This study was designed to evaluate reperfusion therapy, co-administered with high dose glucose-insulin-potassium (GIK) treatment on serum soluble Fas/APO-1 (sFas) and Fas ligand (sFasL) concentration in Acute Myocardial Infarction (AMI) patients. METHODS: Seventy-four patients with AMI underwent reperfusion therapy were randomized into GIK group (n = 35) receiving high-dose GIK for 24 hours or a vehicle group (n = 39). Thirty-four control subjects (NC) were also enrolled in the present study. Strepavidin-biotin ELISA was used to determine the serum sFas and sFasL concentration at baseline and different time point (24 h, 3 d, 7 d and 14 d) after reperfusion. RESULTS: (1) The serum concentration of sFas and sFas-L ([sFas] and [sFas-L]) of AMI patients were significantly elevated at baseline as compared with NC (P < 0.01). (2) The [sFas] in GIK and non-GIK group decreased 24 h after reperfusion (P < 0.01 vs. baseline) and then increased during 3-7 d period (P < 0.01 vs. 24 h). (3) The GIK group demonstrated reduced [sFas] at 14 d (P < 0.01 vs. 7 d), with no concomitant changes in the non-GIK group. (4) The [sFasL] in the GIK and non-GIK group were no significant difference during 3-14 d period. CONCLUSION Owing to cardioprotective effects reported here and by others, a high-dose GIK infusion co-administered with the timely establishment of perfusion should be strongly considered as a treatment of choice for AMI.