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Objective: Previous studies showed a significant association between lower plasma adiponectin levels and higher risk of adverse cardiovascular outcomes in patients with and without type 2 diabetes mellitus (T2DM). Presently, it is uncertain whether lower plasma adiponectin levels are associated with greater plasma thrombin generation in patients with T2DM., Patients and Methods: We studied 82 middle-aged men with non-insulin-treated T2DM [mean age ± SD: 64.1 ± 8 years; median duration of diabetes: 12.5 (inter-quartile range 6-19) years; mean hemoglobin A1c 7.0 ± 0.7%], consecutively attending our diabetes outpatient service over a 6-month period. Using the newly developed fully automated thrombin generation analyzer ST Genesia®, we measured the plasma parameters lag time (LT), time to peak (TP), peak height (PH) and endogenous thrombin potential (ETP) in all participants., Results: In univariable linear regression analyses, lower plasma adiponectin levels were significantly associated with higher plasma thrombin generation parameters, as reflected by higher values of PH (Pearson's r coefficient = - 0.228, p = 0.039) and EPT (r = - 0.293, p = 0.007). Plasma adiponectin levels were not significantly associated with other thrombin generation parameters (LT and TP). Notably, the significant associations of plasma adiponectin levels with thrombin PH and EPT values persisted after adjustment for age and adiposity measures, but they were lost after additional adjustment for plasma triglycerides., Conclusion: Our findings show for the first time the existence of a significant association between lower levels of plasma adiponectin and greater plasma thrombin generation (as assessed by the ST Genesia® analyzer) in men with non-insulin-treated T2DM, which appears to be largely mediated by plasma triglycerides.

Objective: Although there is information on biochemical markers of muscle and cardiac damage following strenuous exercise, little is known about the kinetics of these markers in athletes performing sub-maximal exercise., Material and Methods: Fifteen healthy, trained, Caucasian males took part in a 21-km run. Blood samples were collected before the run, immediately after (post), and 3 h, 6 h and 24 h thereafter. Biochemical markers of muscle and cardiac damage were evaluated on the Modular System, employing proprietary reagents. In no case did the concentration of troponin T increase by >0.03 ng/mL. The values of aspartate aminotransferase (AST), creatine kinase (CK), CK MB, lactate dehydrogenase (LDH) and myoglobin increased significantly immediately after the run and remained elevated 24 h thereafter., Results: The number of subjects with values above the upper limit of the relative reference ranges did not vary throughout the study period for AST and LDH, while it increased significantly for CK, CK MB and myoglobin. The major variation over the pre-run value was recorded for myoglobin (3-fold increment), whereas AST and LDH increased 1.1 and 1.3-fold, respectively., Conclusions: The results suggest the hypothesis that sub-maximal exercise influences the concentration of several biomarkers of muscle damage for up to 24 h with no biochemical signs of myocardial damage.

Xanthine oxidase (XO), a free radical-generating enzyme, is involved in tissue damage produced during exhaustive exercise. Our aim was to test whether allopurinol, a powerful inhibitor of XO, may be effective in preventing exercise-induced tissue damage in soccer players. Twelve soccer players were randomized into two experimental groups. One received allopurinol, before a match of the premier Spanish Football League, and the other placebo. Allopurinol prevented the exercise-induced increase in all the markers of skeletal muscle damage analyzed: creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and myoglobin. Creatine kinase-MB isoenzyme and highly sensitive troponin T, specific biomarkers of myocardial injury, increased significantly in the placebo but not in the allopurinol-treated group after the football match. We also found that the exercise-induced lipid peroxidation, as reflected by malondialdehyde measurements, was prevented after allopurinol administration. However, inhibition of XO did not prevent the increment in the activity of alanine aminotransferase found after the match. No changes in the serum gamma glutamyltransferase activity was found after the match on either the placebo and the allopurinol groups. These two enzymes were determined as biomarkers of liver injury. Allopurinol represents an effective and inexpensive pharmacological agent to prevent tissue damage in soccer players. [ABSTRACT FROM AUTHOR]

Background:Tumour-released DNA in blood represents a promising biomarker for cancer detection. Although epigenetic alterations such as aberrant promoter methylation represent an appealing perspective, the discordance existing between frequencies of alterations found in DNA extracted from tumour tissue and cell-free DNA (cfDNA) has challenged their practical clinical application. With the aim to explain this bias of agreement, we investigated whether protocadherin 10 (PCDH10) promoter methylation in tissue was associated with methylation pattern in matched cfDNA isolated from plasma of patients with colorectal cancer (CRC), and whether the strength of concordance may depend on levels of cfDNA, integrity index, as well as on different clinical-pathological features.Methods:A quantitative methylation-specific PCR was used to analyse a selected CpG site in the PCDH10 promoter of 67 tumour tissues, paired normal mucosae, and matched plasma samples. The cfDNA integrity index and cfDNA concentration were assessed using a real-time PCR assay.Results:The PCDH10 promoter methylation was detected in 63 out of 67 (94.0%) surgically resected colorectal tumours and in 42 out of 67 (62.7%) plasma samples. The median methylation rate in tumour tissues and plasma samples was 43.5% (6.3-97.8%) and 5.9% (0-80.9%), respectively. There was a significant correlation between PCDH10 methylation in cfDNA and tumour tissue in patients with early CRC (P<0.0001). The ratio between plasma and tissue methylation rate increases with increasing cfDNA integrity index in early-stage cancers (P=0.0299) and with absolute cfDNA concentration in advanced cancers (P=0.0234).Conclusion:Our findings provide new insight into biological aspects modulating the concordance between tissues and plasma methylation profiles. [ABSTRACT FROM AUTHOR]