Vitamin D and Physical Activity

Vitamin D is synthesized in the skin following exposure to ultraviolet radiation, producing cholecalciferol, while only a small percentage of the circulating vitamin D is of exogenous origin deriving from food. Following two sequential hydroxylations, in the liver and in the kidneys, vitamin D is fully activated. Although its role in bone physiology and calcium homeostasis is well documented, there is emerging evidence that vitamin D exerts a plethora of additional effects on most tissues regulating the musculoskeletal, cardiovascular, and immune systems as well as energy homeostasis. Its deficiency/insufficiency poses a major public health problem observed in all age groups and regardless of latitude and insolation. In muscles, vitamin D deficiency is associated with a decline in neuromuscular function including muscular strength, walking speed, balance, jumping and sprinting performance, and aerobic capacity, although the evidence is still weak regarding its effects in the young and the athletes. Supplementation counteracts the negative effects of vitamin D deficiency on performance although in individuals with adequate levels of vitamin D, additional supplementation does not appear to enhance further physical capabilities. The aim of this chapter is to review our current understanding of diverse effects of vitamin D in physical performance in athletic and nonathletic populations

Interaction of heat shock protein (hsp90) with the cytoskeleton: potential implication in intracellular transport

In this article we will summarize the details concerning the association of 90kD heat shock protein (hsp90) with cytoskeletal structures and we will discuss the potential involvement of these interactions in the translocation of steroid hormone receptors to the cell nucleus. In cultured mammalian cells hsp90 has been found to be colocalized with both microtubules and cytokeratin intermediate filaments, whereas no association with actin filaments and vimentin intermediate filaments has been established. The colocalization of hsp90 with microtubules and cytokeratin in intact cells rises the possibility that cytoskeletal structures could serve as "rails" for the direct movement of the steroid hormone receptor via association-dissociation with hsp90 molecules from the cytoplasmic site of synthesis to the nuclear site of action.Biomedical Reviews 1994; 3: 27-37

Advanced Modalizing Problems

I present an internal problem for David Lewis’s genuine modal realism. My aim is to show that his analysis of modality is inconsistent with his metaphysics. I consider several ways of modifying the Lewisian analysis of modality, but argue that none are successful. I argue that the problem also affects theories related to genuine modal realism, including the stage theory of persistence and modal fictionalism

The impact of stress on tumor growth: peripheral CRF mediates tumor-promoting effects of stress

<p>Abstract</p> <p>Introduction</p> <p>Stress has been shown to be a tumor promoting factor. Both clinical and laboratory studies have shown that chronic stress is associated with tumor growth in several types of cancer. Corticotropin Releasing Factor (CRF) is the major hypothalamic mediator of stress, but is also expressed in peripheral tissues. Earlier studies have shown that peripheral CRF affects breast cancer cell proliferation and motility. The aim of the present study was to assess the significance of peripheral CRF on tumor growth as a mediator of the response to stress in vivo.</p> <p>Methods</p> <p>For this purpose we used the 4T1 breast cancer cell line in cell culture and in vivo. Cells were treated with CRF in culture and gene specific arrays were performed to identify genes directly affected by CRF and involved in breast cancer cell growth. To assess the impact of peripheral CRF as a stress mediator in tumor growth, Balb/c mice were orthotopically injected with 4T1 cells in the mammary fat pad to induce breast tumors. Mice were subjected to repetitive immobilization stress as a model of chronic stress. To inhibit the action of CRF, the CRF antagonist antalarmin was injected intraperitoneally. Breast tissue samples were histologically analyzed and assessed for neoangiogenesis.</p> <p>Results</p> <p>Array analysis revealed among other genes that CRF induced the expression of SMAD2 and β-catenin, genes involved in breast cancer cell proliferation and cytoskeletal changes associated with metastasis. Cell transfection and luciferase assays confirmed the role of CRF in WNT- β-catenin signaling. CRF induced 4T1 cell proliferation and augmented the TGF-β action on proliferation confirming its impact on TGFβ/SMAD2 signaling. In addition, CRF promoted actin reorganization and cell migration, suggesting a direct tumor-promoting action. Chronic stress augmented tumor growth in 4T1 breast tumor bearing mice and peripheral administration of the CRF antagonist antalarmin suppressed this effect. Moreover, antalarmin suppressed neoangiogenesis in 4T1 tumors in vivo.</p> <p>Conclusion</p> <p>This is the first report demonstrating that peripheral CRF, at least in part, mediates the tumor-promoting effects of stress and implicates CRF in SMAD2 and β-catenin expression.</p

Dietary factors and low-grade inflammation in relation to overweight and obesity

Low-grade inflammation is a characteristic of the obese state, and adipose tissue releases many inflammatory mediators. The source of these mediators within adipose tissue is not clear, but infiltrating macrophages seem to be especially important, although adipocytes themselves play a role. Obese people have higher circulating concentrations of many inflammatory markers than lean people do, and these are believed to play a role in causing insulin resistance and other metabolic disturbances. Blood concentrations of inflammatory markers are lowered following weight loss. In the hours following the consumption of a meal, there is an elevation in the concentrations of inflammatory mediators in the bloodstream, which is exaggerated in obese subjects and in type 2 diabetics. Both high-glucose and high-fat meals may induce postprandial inflammation, and this is exaggerated by a high meal content of advanced glycation end products (AGE) and partly ablated by inclusion of certain antioxidants or antioxidant-containing foods within the meal. Healthy eating patterns are associated with lower circulating concentrations of inflammatory markers. Among the components of a healthy diet, whole grains, vegetables and fruits, and fish are all associated with lower inflammation. AGE are associated with enhanced oxidative stress and inflammation. SFA and trans-MUFA are pro-inflammatory, while PUFA, especially long-chain n-3 PUFA, are anti-inflammatory. Hyperglycaemia induces both postprandial and chronic low-grade inflammation. Vitamin C, vitamin E and carotenoids decrease the circulating concentrations of inflammatory markers. Potential mechanisms are described and research gaps, which limit our understanding of the interaction between diet and postprandial and chronic low-grade inflammation, are identifie

Leptin levels in cord blood and anthropometric measures at birth: a systematic review and meta-analysis

P&gt;Karakosta P, Chatzi L, Plana E, Margioris A, Castanas E, Kogevinas M. Leptin levels in cord blood and anthropometric measures at birth: a systematic review and meta-analysis. Paediatric and Perinatal Epidemiology 2010. The role of intrauterine environment in the development of obesity is increasingly recognised. Adipokines and specifically leptin have been examined as potential biomarkers predicting early development of obesity. We conducted a systematic review and meta-analysis of the epidemiological evidence for the association between leptin levels in cord blood and anthropometric measurements at birth in healthy mother-newborn pairs. A PubMed search was performed between 1994 and 2009 and manual search of reference lists of retrieved articles. Forty-four studies met the inclusion criteria set. All studies reported a positive correlation between leptin levels and birthweight. The combined correlation coefficient (r) was 0.46 [95%CI 0.43, 0.50]. Leptin levels explained 21% of variation in birthweight. Results were similar in males (r = 0.55; 0.40, 0.68) and females (r = 0.60; 0.50, 0.69), and between Caucasians (r = 0.45; 0.39, 0.51) and eastern Asian populations (r = 0.47; 0.37, 0.55). Statistically significant positive correlations were also found for birth length (r = 0.29; 0.23, 0.34) and ponderal index (r = 0.36; 0.31, 0.41). There was no indication of publication bias (Egger’s test P-value = 0.23). This meta-analysis shows a clear but moderate correlation between leptin levels in cord blood and birthweight that is observed in different population groups