The role of vitamin d in autoimmune hepatitis.

Autoimmune hepatitis is an inflammation of the liver characterized by the presence of peri-portal hepatitis, hypergammaglobulinemia, and the serum autoantibodies. The disease is classified into 2 distinct types according to the nature of auto-antibodies. Disturbances of the calcium-parathyroid hormone-vitamin D axis are frequently associated with chronic liver disease. Patients with AIH have a high prevalence of vitamin D deficiency. Genetic studies have provided the opportunity to determine which proteins link vitamin D to AIH pathology, namely, the major histocompatibility complex class II molecules, vitamin D receptors, toll-like receptors, cytotoxic T lymphocyte antigen-4, cytochrome P450 CYP2D6, regulatory T cells (Tregs) and the forkhead/winged helix transcription factor 3. Vitamin D also exerts its effect on AIH through non-genomic factors, namely, mitogen-activated protein kinase signaling pathways, γδT cells, interferon-gamma nitric oxide synthase, and reactive oxygen stress. In conclusion, vitamin D may have a beneficial role in AIH and improves liver function in concanavalin A-induced mouse AIH. Calcitriol is best used for AIH because it is the active form of a vitamin D3 metabolite and its receptors are present in sinusoidal endothelial cells, Kupffer cells, stellate cells of normal livers, and the biliary cell line.

Beneficial role of vitamin D3 in the prevention of certain respiratory diseases.

There is evidence of aberrations in the vitamin D-endocrine system in subjects with respiratory diseases. Vitamin D deficiency is highly prevalent in patients with respiratory diseases, and patients who receive vitamin D have significantly larger improvements in inspiratory muscle strength and maximal oxygen uptake. Studies have provided an opportunity to determine which proteins link vitamin D to respiratory pathology, including the major histocompatibility complex class II molecules, vitamin D receptor, vitamin D-binding protein, chromosome P450, Toll-like receptors, poly(ADP-ribose) polymerase-1, and the reduced form of nicotinamide adenine dinucleotide phosphate. Vitamin D also exerts its effect on respiratory diseases through cell signaling mechanisms, including matrix metalloproteinases, mitogen-activated protein kinase pathways, the Wnt/ß-catenin signaling pathway, prostaglandins, reactive oxygen species, and nitric oxide synthase. In conclusion, vitamin D plays a significant role in respiratory diseases. The best form of vitamin D for use in the treatment of respiratory diseases is calcitriol because it is the active metabolite of vitamin D3 and modulates inflammatory cytokine expression. Further investigation of calcitriol in respiratory diseases is needed.

The role of ß-adrenergic blockers in Parkinson's disease: possible genetic and cell-signaling mechanisms.

Genetic studies have identified numerous factors linking ß-adrenergic blockade to Parkinson's disease (PD), including human leukocyte antigen genes, the renin-angiotensin system, poly(adenosine diphosphate-ribose) polymerase 1, nerve growth factor, vascular endothelial growth factor, and the reduced form of nicotinamide adenine dinucleotide phosphate. ß-Adrenergic blockade has also been implicated in PD via its effects on matrix metalloproteinases, mitogen-activated protein kinase pathways, prostaglandins, cyclooxygenase 2, and nitric oxide synthase. ß-Adrenergic blockade may have a significant role in PD; therefore, the characterization of ß-adrenergic blockade in patients with PD is needed.

The impact of thiamine treatment in the diabetes mellitus.

Thiamine acts as a coenzyme for transketolase (Tk) and for the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes, enzymes which play a fundamental role for intracellular glucose metabolism. The relationship between thiamine and diabetes mellitus (DM) has been reported in the literature. Thiamine levels and thiamine-dependent enzyme activities have been reduced in DM. Genetic studies provide opportunity to link the relationship between thiamine and DM (such as Tk, SLC19A2 gene, transcription factor Sp1, α-1-antitrypsin, and p53). Thiamine and its derivatives have been demonstrated to prevent the activation of the biochemical pathways (increased flux through the polyol pathway, formation of advanced glycation end-products, activation of protein kinase C, and increased flux through the hexosamine biosynthesis pathway) induced by hyperglycemia in DM.Thiamine definitively has a role in the diabetic endothelial vascular diseases (micro and macroangiopathy), lipid profile, retinopathy, nephropathy, cardiopathy, and neuropathy.

The role of vitamin D in asthma.

Vitamin D metabolites are important immune-modulatory hormones and are able to suppress Th2-mediated allergic airway disease. Some genetic factors that may contribute to asthma are regulated by vitamin D, such as vitamin D receptor (VDR), human leukocyte antigen genes (HLA), human Toll-like receptors (TLR), matrix metalloproteinases (MMPs), a disintegrin and metalloprotein-33 (ADAM-33), and poly(ADP-ribosyl) polymerase- 1 (PARP-1). Vitamin D has also been implicated in asthma through its effects on the obesity, bacillus Calmettee Guérin (BCG) vaccination and high vitamin D level, vitamin D supplement, checkpoint protein kinase 1 (Chk1), plasminogen activator inhibitor-1 (PAI-1) and gamma delta T cells (gdT). Vitamin D plays a role in asthma and exerts its action through either genomic and/or non-genomic ways.

Impact of vitamin D in the treatment of tuberculosis.

Tuberculosis (TB) is a major global health problem and often coincides with nutritional deficiency. In fact, vitamin D deficiency has been reported among TB patients, and vitamin D receptor polymorphisms are associated with susceptibility to Mycobacterium tuberculosis. High doses of vitamin D were widely used to treat TB patients in the preantibiotic era. This approach was successful: vitamin D can suppress intracellular growth of M tuberculosis in vitro. Vitamin D also induced the expression of cathelicidin, which is involved in the first line of defense in TB patients. Thus, vitamin D may have a role in TB treatment, and further investigation is needed.

The beneficial role of vitamin D and its analogs in cancer treatment and prevention.

BACKGROUND: Cancer is the leading cause of death in the United States, and the probability of developing cancer increases dramatically with age. Interestingly, vitamin D deficiency is also recognized more often in people of advanced ages. A potential relationship between vitamin D deficiency and cancer has been reported in the literature. METHOD: Review Medline database literature and discuss the relationship between vitamin D status and cancer. RESULTS: Environmental (including seasonal and geographic) and genetic factors contribute to the development of both vitamin D deficiency and cancer. The vitamin D receptor is present in many tissues, especially in malignant cells, and may contribute to the successful use of vitamin D and its analogs in the treatment of some cancer patients. CONCLUSION: Further investigation of the role of vitamin D in the treatment of cancer is warranted.

Vitamin D and cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of death among patients with end-stage renal disease (ESRD). Vitamin D deficiency accompanies the loss of kidney function and is extremely common. Treatment with active vitamin D has improved survival rate in dialysis patients. The relationship between vitamin D and CVD has been reported in the literature. Genetic factors have been known to cause both vitamin D deficiency and CVD. Vitamin D receptor is found in the heart muscle. Vitamin D is reported to be involved in the pathogenesis of many cardiovascular problems. Certainly, vitamin D has an important role in modulating CVD.

Adult hypophosphatasia and a low level of red blood cell thiamine pyrophosphate.

OBJECTIVE: To report the first adult case of hypophosphatasia and absence of intestinal alkaline phosphatase (ALP) isoenzymes associated with a low level of red blood cell thiamine pyrophosphate. METHODS: We describe the clinical manifestation and laboratory findings in our patient and discuss underlying factors that potentially contribute to her condition. RESULTS: A 33-year-old Vietnamese-American female was referred for a long history of low levels of serum ALP and absence of intestinal ALP isoenzyme. She had a normal level of urinary phosphoethanolamine and a high level of plasma pyridoxal-5p-phosphate. She was found to have a low level of red blood cell thiamine pyrophosphate. CONCLUSION: Our adult case of hypophosphatasia presented with an absence of intestinal ALP isoenzyme that might result in decreasing the absorption of thiamine in the intestinal tract. Therefore, the thiamine level should be considered in hypophosphatasia with absence of intestinal ALP isoenzyme.

The role of vitamin D in protecting type 1 diabetes mellitus.

The relationship between autoimmune diabetes or type 1 diabetes mellitus and vitamin D has been reported in the literature. Many factors, environmental and genetic, have been known, as risk factors, to cause both type 1 diabetes and vitamin D deficiency. Vitamin D treatment has improved or prevented type 1 diabetes mellitus in animals and humans. Vitamin D also has been known to protect from autoimmune diseases in animal models. Therefore, it would be interesting to review the role of vitamin D in type 1 diabetes mellitus.