We evaluated the association between 2 genetic polymorphisms known to be involved in fitness and performance, and anthropometric features, body composition, and athletic performances in young male soccer players with the goal of identifying genetic profiles that can be used to achieve maximal results from training. One hundred twenty-five medium-high-level male soccer players were genotyped for angiotensin-converting enzyme (ACE) I/D, and vitamin D receptor (VDR) FokI gene polymorphisms and scored for anthropometric measurements, body composition, and athletic performance. Body mass index, fat mass, fat-free mass, resistance, reactance, impedance, phase angle (PA), and body cell mass were measured. Athletic performance was evaluated by squat jump, countermovement jump (CMJ), 2-kg medicine ball throw, 10- and 20-m sprint time. We observed that the homozygous ff genotype of the VDR gene was significantly more represented in young soccer players than in a matched sedentary population. Values of reactance and PA were differently distributed in ACE and VDR genotypes with high mean values in subjects with DD (ACE) and FF (VDR) genotypes. No correlation was observed between ACE or VDR genotypes and 2-kg medicine ball throw, 10- and 20-m sprint times. The ID genotype of ACE was associated with the best performances in squat jump and CMJ. Our results suggest that determination of ACE and VDR genotypes might help select those young athletes harboring the most favorable genetic potential to succeed in soccer.

Cadmium is an environmental pollutant inducing numerous pathological effects, including neurological disorders and brain diseases. However, little is known about the molecular mechanisms of cadmium in affecting neurons and in inducing neurotoxicity in the development of the human brain. We have recently established, cloned, and propagated in vitro a primary long-term cell culture (FNC-B4) obtained from the human fetal olfactory neuroepithelium. In the present study, we show that different concentrations of cadmium chloride (CdCl(2)) induced dose-dependent biological effects in FNC-B4 cells. A low concentration (10 microM) of CdCl(2) stimulated neuroblast growth, whereas a high concentration (100 microM) inhibited the growth and the viability of neuroblasts inducing morphological and cytoskeletal alterations as well as apoptotic cell death. We also observed that CdCl(2) affected, in a dose-dependent manner, the differentiation of FNC-B4 neuroblasts, with increased mRNA and protein levels of differentiation markers and decreased expression levels of neuronal stem markers. Furthermore, differentiated cells co-expressed glial and neuronal markers. We suggest that CdCl(2) in FNC-B4 neuroblasts might represent a selective cue by which, in a heterogeneous primary culture, the more differentiated mature cells die, whereas the undifferentiated cells, at the same time glial and neuronal progenitors, are forced to access a state of differentiation.

Background and Objective: In patients with advanced cancer, cachexia correlates with low performance status and poor quality of life. In addition, cachexia may be associated with reduced response to chemoradiotherapy and a poor prognosis in cancer patients. Nearly all forms of cachexia are closely associated with chronic inflammation and elevated levels of inflammatory and pro-inflammatory circulating factors, including C-reactive protein (CRP), which is considered a valid laboratory and clinical marker. Among the different pathways involved in the production of inflammatory cytokines and chemokines, the vitamin Dvitamin D receptor (VDR) axis plays a fundamental role.In this study, we explore the possible association between CRP and key factors pertaining to the vitamin D axis -in particular, VDR gene polymorphisms -in cancer patients with cachexia. Although certain tumor types are more commonly associated with cachexia, even within the same tumor type there are significant differences in the extent and duration of cachexia. Such variations may be due to polymorphisms of the VDR gene that could lead to cachexia-prone genotypes or to cachexia-resistant genotypes. Identification of such genotypes could be very helpful in the management of cancer patients. Methods: Forty-three cancer patients were recruited by the Nutritional Unit of the Prato Hospital. Data on age, gender, type of cancer, stage of cancer, and nutritional assessment, as well as transferrin, ferritin, albumin, and CRP levels, were collected. Genomic DNA was extracted from peripheral blood leukocytes and amplified by polymerase chain reaction. BsmI, ApaI, TaqI, and FokI polymorphisms of the VDR gene were investigated using the respective restriction enzymes. For the different VDR polymorphisms, the absence or presence of the restriction sites were designated with capital or small letters, respectively. For example, for the BsmI polymorphism, the presence of the undigested fragment identified the B allele, whereas the presence of the digested fragment identified the b allele. Results: Cancer patients with cachexia have higher CRP levels compared with non-cachectic cancer patients, independently from the genotype. In cachectic patients, the presence of specific VDR BsmI and TaqI alleles was associated with higher CRP levels. In particular, the VDR b and T alleles were more frequent in cachectic cancer patients with elevated CRP levels than in cachectic patients with normal CRP levels. Conclusion: From these results, we hypothesize that there is an association between BsmI and TaqI VDR gene polymorphisms and the cachectic syndrome. In particular, we propose that in cancer patients, the concomitance of b and T alleles with elevated CRP levels may represent an early clinical predictor for the development of a more aggressive form of cachexia.

Polymorphisms of the vitamin D receptor gene, known to be associated with the highest responses to vitamin D receptor agonists, are also associated with the highest responses to GcMAF. These results highlight the role of the vitamin D axis in chronic kidney disease, an axis which includes vitamin D, its receptor and vitamin D-binding protein-derived GcMAF.

The effects of Gc protein-derived macrophage-activating factor (GcMAF) have been studied in cancer and other conditions where angiogenesis is deregulated. In this study, we demonstrate for the first time that the mitogenic response of human peripheral blood mononuclear cells (PBMCs) to GcMAF was associated with 3'-5'-cyclic adenosine monophosphate (cAMP) formation. The effect was dose dependent, and maximal stimulation was achieved using 0.1 ng/ml. Heparin inhibited the stimulatory effect of GcMAF on PBMCs. In addition, we demonstrate that GcMAF (1 ng/ml) inhibited prostaglandin E(1)- and human breast cancer cell-stimulated angiogenesis in chick embryo chorionallantoic membrane (CAM) assay. Finally, we tested different GcMAF preparations on CAM, and the assay proved to be a reliable, reproducible and inexpensive method to determine the relative potencies of different preparations and their stability; we observed that storage at room temperature for 15 days decreased GcMAF potency by about 50%. These data could prove useful for upcoming clinical trials on GcMAF.