Vitamin D Deficiency

Vitamin D is the topic for many discussions in the scientific community. Nowadays, a different interpretation of this secosteroid hormone is needed. Today the term "vitamin" may be considered outdated. This compound may be correctly be called a vitamin only when it is administered to humans or animals that suffer from its deficiency. This book attempts to clarify the role of Vitamin D deficiency in many pathological processes in the whole organism. Chapters in this book cover such issues as the earliest clinical and preclinical investigations of the consequences of Vitamin D deficiency for cognitive, cardiovascular, metabolic, immune, and renal disorders

Vitamin D and neurological diseases: An endocrine view

Vitamin D system comprises hormone precursors, active metabolites, carriers, enzymes, and receptors involved in genomic and non-genomic effects. In addition to classical bone-related effects, this system has also been shown to activate multiple molecular mediators and elicit many physiological functions. In vitro and in vivo studies have, in fact, increasingly focused on the "non-calcemic" actions of vitamin D, which are associated with the maintenance of glucose homeostasis, cardiovascular morbidity, autoimmunity, inflammation, and cancer. In parallel, growing evidence has recognized that a multimodal association links vitamin D system to brain development, functions and diseases. With vitamin D deficiency reaching epidemic proportions worldwide, there is now concern that optimal levels of vitamin D in the bloodstream are also necessary to preserve the neurological development and protect the adult brain. The aim of this review is to highlight the relationship between vitamin D and neurological diseases

The Effect of Calcineurin Inhibition on the Expression and Activation of Renal Electrolyte Transporters

Tacrolimus (FK506) is a calcineurin inhibitor (CNI), and the main immunosuppressant used in organ transplantation. It causes complications such as hypertension, hyperkalaemia, hypercalciuria and acidosis. Together with insulin resistance, dyslipidaemia and obesity, they comprise the metabolic syndrome. CNIs induce hypertension through the activation of the WNK-NCC cascade, causing an increase in sodium chloride reabsorption, and phosphorylation is an important post-translational modification that alters the activity of the members in the WNK-NCC cascade. Using quantitative phosphoproteomics and several bioinformatic techniques, a phosphoproteome profile of the renal cortices from FK506-treated mice was generated and phosphoproteins involved in renal tubular transport were identified. In this data, AKT was phosphorylated by FK506 and was suggested to act as the intermediary protein in the calcineurin-WNK cascade. In addition, ERK1/2 was also dysregulated by FK506 and was suggested to regulate NCC through the WNK4-ERK1/2 pathway. The phosphoproteome profile also revealed several FK506-dysregulated phosphoproteins that are involved in sodium, acid-base, glucose and potassium handling. CNIs have been suggested to cause hypercalciuria through a decrease in TRPV5 and calbindin-D28K expression, however, the effect of FK506 on other regulatory and transport proteins involved in calcium handling is unclear. In contrast to previous studies, FK506 did not dysregulate TRPV5 expression, but instead increased the expression of the basolateral calcium transporters, NCX1 and PMCA. Based on these findings, a novel mechanism explaining CNI-induced hypercalciuria, driven by the activation of NCC, is proposed and the relationship between sodium and calcium handling in the DCT is discussed. The effects of calcineurin inhibition on renal electrolyte transporters and their potential regulators induce salt-sensitive hypertension and hypercalciuria. The findings presented in this thesis contribute to the understanding of the underlying mechanism that governs sodium and calcium handling in the DCT and full elucidation of this molecular machinery is of interest and clinical importance