Cell-free plasma DNA as a novel marker of aseptic inflammation severity related to exercise overtraining

BACKGROUND: Circulating free plasma DNA is implicated in conditions associated with tissue injury, including exercise-induced inflammation, and thus is a potential marker for athletic overtraining. METHODS: We measured free plasma DNA along with C-reactive protein (CRP), creatine kinase (CK), and uric acid (UA) in 17 recreationally trained men participating in a 12-week resistance training regimen (8 resistance multi-joint exercises selected to stress the entire musculature: bench press, squat, leg press, snatch, hang clean, dead lifts, barbell arm curls, and rowing), consisting of 4 training periods (t1, t2, t3, and t4). RESULTS: Plasma DNA concentrations increased markedly after t1, t2, and t3 and returned to baseline after t4. There were substantial differences between t2 and t1 and between t3 and t2 plasma DNA concentrations. CRP increased by 300% after t2 and by 400% after t3 (there was no difference between t2 and t3 CRP values) compared with baseline (t0). CK increased only after t3. UA increased after t2 and t3, with a greater increase after t3. CONCLUSIONS: This study demonstrates that, after chronic excessive resistance exercise, plasma DNA concentrations increase in proportion to training load, suggesting that plasma DNA may be a sensitive marker for overtraining-induced inflammation.     

Clinical and molecular description of a fetus in prenatal diagnosis with a rare de novo ring 10 and deletions of 12.59 Mb in 10p15.3-p14 and 4.22 Mb in 10q26.3

Ring chromosomes are rare cytogenetic findings and are mostly associated with an abnormal phenotype. We report on the prenatal diagnosis of a ring chromosome 10 in a fetus in which talipes equinovarus was incidentally found during routine obstetric ultrasound at 22 weeks of gestation. Amniocentesis was undertaken and cytogenetic analysis revealed a de novo non-mosaic apparently stable ring chromosome 10 replacing one of the two homologs. Multiplex Ligation-dependent Probe Amplification (MLPA) revealed subtelomeric deletions in both the short and long arm of chromosome 10. Analysis with high resolution micro-array based comparative genomic hybridization (array-CGH), defined the ring chromosome as del 10p15.3-p14 (12.59 Mb in size) and del 10q26.3 (4.22 Mb in size) and revealed the genes that are deleted. After elected termination of the pregnancy at 27th week of gestation a detailed autopsy of the fetus allowed for genotype-phenotype correlations. To our knowledge, this is the first case of a de novo ring chromosome 10 which is reported during prenatal diagnosis and is thoroughly investigated with array CGH and autopsy study.     

A rare example that coinheritance of a severe form of beta-thalassemia and alpha-thalassemia interact in a "synergistic" manner to balance the phenotype of classic thalassemic syndromes

The coinheritance of beta-thalassemia major with the genotype of Hb H disease is extremely rare, with few reported cases. We investigated the hematological, biochemical, biosynthetic, molecular and pathophysiological parameters to evaluate a rare male patient with this compound syndrome. The patient was studied at first diagnosis during hospitalization at 50 years of age and subsequently followed up for more than a year. Examinations included full hematological, biochemical, biosynthetic, molecular, pathophysiological and clinical parameters. Besides standard parameters, we additionally measured reticulocyte hemoglobin content (CHr), erythropoietin (Epo), soluble transferrin receptors (sTfR), oxygen pressure at 50% hemoglobin saturation (P50), 2,3-bisphosphoglycerate (2,3-BPG), total glutathione (GSHt), oxidized glutathione (GSSG), malonyldialdehyde (MDA), nontransferrin-bound iron (NTBI), vitamins A and E. The male patient was first hospitalized for a 2-day period at 50 years of age, following the finding of marked anemia (hematocrit 20%) during a blood test to investigate the cause of fatigue in the absence of weight-loss or other notable symptomatology. He had never been transfused, maintaining Hb 85-95 g/l. Definitive diagnosis was achieved through DNA studies, which showed coexistence of beta-thalassemia major (IVSI-6 T > C/IVSI-I G > A) with Hb H disease (-alpha(3.7)/-(Med)). Alpha/non-alpha globin chain biosynthesis was completely balanced. Parameters demonstrated a well-compensated anemia with ineffective erythropoiesis and oxidative stress, which was ameliorated following splenectomy. In conclusion, this case is a remarkable example that the coinheritance of severe forms of beta-thalassemia and alpha-thalassemia interact in a "synergistic" manner to almost complete balance the symptoms of classic thalassemia syndromes.     

Heterogeneity of plasma glucagon: patterns in patients with chronic renal failure and diabetes.

Immunoreactive plasma glucagon (IRG) in normal subjects and patients with chronic renal failure, diabetic ketoacidosis and diagetic hyperosmolar syndrome circulates in several forms. In the diabetic patients most IRG eluted coincidentally with the extracted, purified pancreatic hormone (MW3500), while in normal subjects a high molecular weight component predominated. In striking contrast, the major component of plasma IRG in patients with chronic renal failure was of intermediate size (MW +/- 9000), consistent with proglucagon. The accumulation of this form of IRG suggests that the kidney plays an important role in its metabolism. If there are differences in the biological activity of the various circulating components of IRG, the significance of immunoreactive glucagon levels in some disease states will require reassessment.     

Cardiac systolic function in Greek children with obstructive sleep-disordered breathing

BackgroundObstructive sleep-disordered breathing (SDB) in children has been associated with increased ventricular strain and decreased left ventricle (LV) diastolic function. The aim of this study was to assess systolic myocardial function in children with SDB of variable severity.MethodsChildren who were referred for polysomnography during the study period underwent echocardiography (two-dimensional, Doppler and tissue Doppler imaging).ResultsA total of 46 subjects (age 6.4 ± 2.6 years) were recruited. Fourteen of them had moderate-to-severe SDB (obstructive apnea-hypopnea index (OAHI): 16.6 ± 11.6 episodes/h), 13 children had mild SDB (OAHI: 3.1 ± 0.7 episodes/h) and 19 subjects had primary snoring (OAHI: 1.2 ± 0.6 episodes/h). Children with moderate-to-severe SDB had significantly lower LV shortening fraction (SF) and ejection fraction (EF) than subjects with primary snoring (p < 0.05). SF in moderate-to-severe SDB, mild SDB and primary snoring groups was: 34.3 ± 5.5%, 36.9 ± 3.2% and 37.7 ± 4.4%, respectively, and EF: 66.9 ± 7.9%, 71.7 ± 6.4% and 72.3 ± 5.9%, respectively. OAHI, age, and systolic blood pressure were significant predictors of SF and EF (p < 0.01).ConclusionsIn children with obstructive SDB, LV systolic function is inversely associated with severity of intermittent upper airway obstruction during sleep.