Peripheral signals of energy homeostasis as possible markers of training stress in athletes: a review

The importance of physical exercise in regulating energy balance and ultimately body mass is widely recognized. There have been several investigative efforts in describing the regulation of the energy homeostasis. Important in this regulatory system is the existence of several peripheral signals that communicate the status of body energy stores to the hypothalamus including leptin, adiponectin, ghrelin, interleukin-6, interleukin-1β, and tumor necrosis factor-α—different cytokines and other peptides that affect energy homeostasis. In certain circumstances, all these peripheral signals may be used to reveal the condition of the athlete as the result of several months of prolonged exercise training. These hormone and cytokine concentrations characterize a physical stress condition in which different hormone and cytokine responses are apparently linked to changes in physical performance. The possibility to use these peripheral signals as markers of training stress (and possible overreaching/overtraining) in elite athletes should be considered. These measured hormone and cytokine levels could also be used to characterize the physical stress of single exercise session, as the hormone and cytokine response to exercise may actually be a response to the concurrent energy deficit. In summary, different peripheral signals of energy homeostasis may be sensitive to changes in specific training stress and may be useful for predicting the onset of possible overreaching/overtraining in athletes.     

QRS duration in high-resolution methods and standard ECG in risk assessment after first and recurrent myocardial infarctions

Background: Prolonged QRS duration (QRSd) is associated with increased mortality after myocardial infarction (MI). Only little data exist about its predictive ability and relationships to clinical variables in the present era of active treatment of myocardial ischemia and cardiac dysfunction. We investigated whether QRSd in high-resolution methods and standard ECG predict arrhythmic events and cardiac death in post-infarction patients with cardiac dysfunction and how it relates to clinical variables, with a special emphasis on history of previous MI.
Methods and Results: Patients (n = 158) with acute MI and cardiac dysfunction had magnetocardiography (MCG), signal-averaged ECG (SAECG), and ECG registered at discharge. Patients with a previous MI had significantly longer QRSd although their left ventricular function was almost similarly impaired. During the mean follow-up of 50 ± 15 (range 1–72) months, 32 patients died and 17 (53%) of the deaths were classified as cardiac. Eighteen patients had an arrhythmic event. QRSd >121 ms in MCG and >114 ms in SAECG were significant predictors of arrhythmic events and cardiac death, whereas QRSd in ECG predicted only cardiac death. In multivariate analysis, QRSd in MCG (hazard ratio (HR) = 3.6, P = 0.007) and SAECG (HR = 4.6, P = 0.016) predicted only arrhythmic events, whereas QRSd in ECG was an independent predictor of cardiac death.
Conclusions: Prolonged QRSd in MCG and SAECG are powerful indicators of the arrhythmia substrate in post-infarction patients with cardiac dysfunction, whereas prolonged QRSd in standard ECG associates with increased risk of cardiac death.     

The influence of serum ghrelin,IGF axis and testosterone on bone mineral density in boys at different stages of sexual maturity

The aim of our study was to examine the relationship between bone mineral density (BMD) and serum ghrelin, insulin-like growth factor-1 (IGF-1), IGF-binding protein 3 (IGFBP-3), and testosterone levels in boys at different stages of puberty. The study included 60 healthy nonobese Estonian schoolboys at the age of 10–18 years. Subjects were divided in three groups (20 boys in each) based on the results of self-assessment using illustrated questionnaire of pubertal stage (G1, I; G2–G3, II; G3–G4, III). Morning fasting blood samples were collected for analysis of ghrelin, testosterone, IGF-1, and IGFBP-3. Total body BMD, lumbar BMD, lumbar apparent volumetric BMD (BMAD), and bone mineral content (BMC) were measured by DXA. Serum testosterone concentration was the most important biochemical predictor of BMD in the total group, explaining 48.8% of variability in total body BMD, 51.4% in lumbar BMD, and 36.8% in lumbar BMAD. Body mass and height were both related to BMD and BMC throughout puberty. The serum IGF-1/IGFBP-3 ratio was correlated with serum testosterone (r = 0.69) and ghrelin (r = −0.58) levels, but also with total BMD (r = 0.39), lumbar BMD (r = 0.42; P < 0.001 in all cases), BMAD (r = 0.29; P < 0.01), and total BMC (r = 0.48; P < 0.001). We conclude that serum testosterone concentration and serum IGF-1/IGFBP-3 molar ratio are the major determinants of bone mineral density in boys at different pubertal stages. Serum ghrelin concentration did not appear to have a direct independent effect on BMD. If present, the association may be mediated through sex hormones and the GH-IGF-I axis.     

Clinical predictors of renal allograft histopathology: a comparative study of single-lesion histology versus a composite, quantitative scoring system

BACKGROUND: Progressive injury that is refractory to conventional immunosuppression remains the major hurdle to indefinite survival of transplanted organs. Several clinical risk factors of chronic renal allograft rejection have been identified; although some (e.g., acute rejection) are direct manifestations of immunological injury, others (e.g., donor age) have been more difficult to conceptually link with graft dysfunction. METHODS: We conducted formal multivariate statistical analyses to reveal associations between established clinical risk factors and allograft histopathology. In a multicenter protocol biopsy-controlled study, 17 clinical risk factors were studied in relation to either the composite Chronic Allograft Damage Index (CADI) score or, to each of eight individual histological indices, using multiple linear regression with forward selection. RESULTS: Nine clinical risk factors were not significantly associated with any histopathological index. Four (donor age, acute rejection, recipient age, and cold ischemia time) were associated both with the total CADI score and, to varying extents, with the individual histopathological indices. In our analysis, clinical risk factors accounted for, at best, only about 60% of the interindividual variation in histopathological score. CONCLUSIONS: Our study reveals a missing link between specific clinical risk factors and early histopathological findings that are known to presage accelerated failure of clinically healthy grafts. Given the complex relationship between clinical risk factors, early histopathological changes, and graft outcome, we conclude that composite, quantitative histological indices are best suited to for evaluation of the histological status of the transplant.     

In situ hybridisation of chick embryos with p53-specific probe and their immunostaining with anti-p53 antibodies

Tumor-suppressor protein p53 is an important regulator of cell cycle and apoptosis. On the level of embryo extracts it has been shown earlier that both p53 protein and mRNA are expressed in developing chicken. Here we describe the expression patterns of p53 mRNA and protein in developing chicken embryos (stages 2–12) using in situ hybridisation and immunostaining with p53-specific monoclonal antibody Mab421. p53 mRNA is equally localised all over the embryo in the stages observed. According to electron microscopy data a subfraction of p53 mRNA is bound to dissolving yolk granules expressing acid phosphatase activity characteristic for lysosomes. Protein p53 is synthesised starting from the medium primitive streak stage (stage 3) and reaches its maximum level at the full primitive streak stage. During these stages protein p53 is distributed evenly across the embryos. After gastrulation p53 protein remains visible at higher levels only in certain anlages and areas. In developing nervous system the expression is observable in neuroectoderm, during the closure of the neural tube and in mesenchyme in the area of migrating neural crest cells. In cardiogenesis protein p53 is expressed during formation of tubular heart in the epimyocardium, endocardium and cardiac jelly. p53 protein localises in the neurocoele (obviously connected with cellular debris) and cardiac jelly. Our data support the role of p53 in early development, especially during embryo gastrulation, the development of central nervous system, neural crest and heart. In some cases increased p53 amounts colocalise with the areas of intensive epithelium-mesenchyme transition. Accepted: 22 May 2001     

Relation of magnetocardiographic arrhythmia risk parameters to delayed ventricular conduction in postinfarction ventricular tachycardia

Time-domain late field and intra-QRS fragmentation parameters in magnetocardiography (MCG) identify patients prone to VT after myocardial infarction. This study investigated if they are related to slow ventricular conduction and affected by arrhythmia surgery. Twenty-two patients with old myocardial infarction undergoing map-guided subendocardial resection to treat sustained VT were included. Bipolar electrograms were recorded during operation using an epicardial jacket and endocardial balloon electrode array. The time from the QRS onset to the end of local ventricular excitation in each electrogram was measured during sinus rhythm. Multi-channel MCG was recorded before and after operation and filtered QRS duration (QRSd), root mean square amplitude of the magnetic field strength during the last 40 ms of the QRS complex (RMS40), duration of the low amplitude signal < 300 fT (LAS300), fragmentation index M (M), and fragmentation score S (S) were determined. All patients had one or two VT foci localized and resected. MCG parameters correlated with time to the latest end of ventricular excitation; r = 0.45 for QRSd (P = 0.035), r = 0.64 for M (P = 0.001), and r = 0.73 for S (P < 0.001). The correlations were even better in patients with anterior infarction (e.g., r = 0.87 for QRSd, P < 0.001; r = 0.91 for M, P < 0.001). The operation reduced the abnormalities in MCG parameters and 20 of the 21 patients tested postoperatively became noninducible. MCG parameters indicating postinfarction arrhythmia propensity are related to delayed ventricular conduction. Abolition of the arrhythmia substrate reverses the abnormality of these parameters.