Konrad Walczak

Decreased integrity of exercise-induced plasma cell free nuclear DNA - negative association with the increased oxidants production by circulating phagocytes

Objective Strenuous exercise increases circulating cell free DNA (cf DNA) and stimulates blood phagocytes to generate more reactive oxygen species (ROS) which may induce DNA strand breaks. We tested whether: (A) elevated cf DNA in response to three repeated bouts of exhaustive exercise has decreased integrity; (B) each bout of exercise increases luminol enhanced whole blood chemiluminescence (LBCL) as a measure of ROS production by polymorphonuclear leukocytes; (C) there is an association between integrity of cf DNA and LBCL. Methods Eleven average-trained men performed three treadmill exercise tests to exhaustion at speed corresponding to 70% of their individual VO2 max separated by 72 hours of resting. Pre-and post-exercise concentrations and integrity of cf nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) were determined with real-time PCR along with measurement of resting and fMLP-stimulated LBCL. Results Each bout increased concentrations of cf n-DNA by more than 10-times which was accompanied by about 2-times elevated post-exercise rLBCL and fMLP-LBCL (p<0.05). Post-exercise cf n-DNA integrity (integrity index, I206/78) decreased after the first (0.59±0.19 vs. 0.48±0.18, p<0.05) and second (0.53±0.14 vs. 0.44±0.17, p<0.05) bout of exercise. There were negative correlations between I206/78 and rLBCL > IJ–0.37, p<0.05) and I206/78 and fMLP-LBCL (ϱ =–T6*T4Ep<0.05) – analysis of pooled pre-and post-exercise data (n = 66). Although cf-mt DNA rose by about 2-times (p<0.05) after the second and third bout, its integrity (I218/97) did not alter in response to exercise. Conclusions Repeated bouts of exhaustive exercise caused increase in cf n-DNA with decreased integrity which correlated with increased ROS production by circulating polymorphonucler leukocytes. This suggests that oxidants may be involved in the release of cf n-DNA and cf n-DNA strand breaks in response to exhaustive exercise.

Repeated bouts of exhaustive exercise increase circulating cell free nuclear and mitochondrial DNA without development of tolerance in healthy men

Objective Acute single strenuous exercise increases circulating cell free DNA (cf DNA). We tested whether three repeated bouts of exhaustive exercise induced the cf DNA response without development of tolerance in healthy men. Methods Eleven average-trained men (age 34.0±5.2 years, body mass index 26.2±3.1 kg/m2, maximal oxygen consumption—VO2max 49.6±4.5 ml/kg*min) performed three treadmill exercise tests to exhaustion at speed corresponding to 70% VO2max separated by 72 hours of resting. Blood was collected before and after each bout of exercise for determination of cell free nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) by real-time PCR, selected markers of muscle damage, and blood cell count. Results Each bout induced the increase (p<0.05) in plasma cf n-DNA: from 3.4±1.4 to 38.5±27.5, from 4.1±3.3 to 48.5±26.2, and 3.1±1.6 to 53.8±39.9 ng/mL after the first, second, and third exercise, respectively. In a congruent way, cf mt-DNA rose significantly after the second (from 229±216 to 450±228*103 GE/mL) and third bout of exercise (from 173±120 to 462±314*103 GE/mL). Pre-exercise cf mt-DNA decreased (p<0.05) by 2-times (from 355±219 before the first bout to 173±120*103 GE/mL before the third bout) over the study period and were accompanied by significant increase in white blood cells, platelets, creatine kinase, creatinine and lactate after each bout. However, the exercise induced percentage increment of cf n-DNA was always many times higher than corresponding increments of the afore-mentioned markers at any occasion. Conclusions Repeated bouts of exhaustive exercise induced remarkable increase in circulating cf n-DNA without signs of tolerance development. Baseline cf mt-DNA decreased in response to series of strenuous exercise. Since percentage increments of cf n-DNA in response to exercise were many times higher than those observed for other markers, measurement of circulating cf n-DNA could be a sensitive tool for monitoring acute exercise effects in human body.

24-hour blood pressure monitoring and renal function in patients with type 1 diabetes

Background and aims. Dipping profile in ambulatory blood pressure monitoring (ABPM) may be a good predictor of target organ damage in patients with type 1 diabetes. The aim of the study was to analyze the correlation between the blood pressure profile in ABPM and other predictors of early kidney damage in type 1 diabetes. Material and methods. We examined 132 type 1 diabetes patients with normal blood pressure and 22 type 1 diabetes patients treated with antihypertensive drugs. ABPM was performed in each patient. Urine albumin to creatinine ratio (UACR) was assessed and estimated glomerular filtration rate (eGFR) was estimated based on serum cystatin C concentration. The association between blood pressure profile in ABPM and renal function was analyzed. Results. In normotensive patients dipper status did not have any impact on renal function. Non-dippers had lower day systolic and diastolic blood pressure and higher night systolic and diastolic blood pressure than dippers. Day systolic blood pressure was negatively correlated with eGRF estimated with cystatin C. In hypertensive patients non-dippers had higher urine albumine to creatinine ratio than dippers. Conclusions. In normotensive type 1 diabetic patients non-dipping status does not seem to be good predictor of early renal complications. However, in type 1 diabetics treated for hypertension, non-dipping could reflect probable kidney damage. GFR estimated with cystatin C could be more sensitive than albuminuria predictor of early kidney damage in type 1 diabetes.