25-OH Vitamin D3 Research Articles

Gene Set Enrichment Analysis Suggests That Increased Rituximab-Mediated NK Cell Cytotoxicity after Vitamin D Substitution Is Driven By Upregulation of Interferon Alpha (IFN-a) Isoforms

Introduction: We recently showed that vitamin D deficiency leads to decreased overall survival of DLBCL-patients treated with rituximab-chemotherapy (Bittenbring et al, JCO, 2014). We hypothesized that rituximab-mediated NK cell-cytotoxicity is more effective at higher vitamin D levels. This was confirmed by vitamin D substitution of healthy volunteers, which increased their rituximab-mediated cytotoxicity in vitro against the Daudi lymphoma cell line. To unveil the molecular mechanisms behind this finding, resting NK cells before and after vitamin D supplementation were isolated from those volunteers and a whole transcriptome analysis was performed.Methods: We collected PBMCs from eight healthy volunteers with vitamin D deficiency before and after vitamin D substitution to > 30 ng/ml 25-OH vitamin D3. NK cells were isolated from PBMCs by magnetic depletion of all non-NK cells. Purity of the CD16+ cells was confirmed by flow cytometry. After isolating total RNA, we performed a microarray analysis using an Affymetrix Gene-Chip 2.0 ™. The signals were normalized using the LMA algorithm. For pathway analysis, gene set enrichment analysis (GSEA) was used. A two-step approach was chosen. Firstly, we separated 7.705 genes due to their involvement in the NK cell-mediated immune response according to the Gene Ontology database, irrespective of their differential expression. This dataset was used separately for specific analysis of the NK cell-cytotoxicity pathway to increase sensitivity. Secondly, the complete data set of 48.145 genes was used in an exploratory analysis in an attempt to screen for other dysregulated pathways involved in the immune response and vitamin D homeostasis. We used gene sets provided from the Molecular Signature Database. A significance level of < 0.05 for p and False Discovery Rate (FDR) was chosen. Real-time quantitative PCR was performed to confirm the results.Results: The NK cell-associated cytotoxicity pathway was found to be significantly upregulated after restoration of normal vitamin D levels in the specific analysis. The most significantly overexpressed genes in the gene set were five IFN-α subtypes (IFN-α2, IFN-α4, IFN-α6, IFN-α7, and IFN-α10) as well as IFN-κ. The exploratory analysis showed an upregulation of the response to type I interferon pathway and regulation of type I interferon mediated signaling pathway. The most upregulated genes in those pathways were again the IFN-α subtypes mentioned above. Other pathways involved in the immune response were found to be downregulated after vitamin D substitution, like interferon gamma response; cytokine production and chemotaxis. The common denominator of these pathways was the downregulation of three toll-like receptor genes (TLR-8, TLR-7, TLR-2).Conclusion: The increased expression of specific IFN-α subtypes could explain the increased rituximab-mediated NK cell-cytotoxicity after vitamin D substitution in deficient individuals. To the best of our knowledge, this is the first study to suggest a role for vitamin D in IFN-α regulation. TLRs are known to stimulate cytokine production in NK cells including IFN-α. It can be assumed, that the observed upregulation of IFN-α genes after vitamin D substitution leads to a negative feedback on positive regulators of cytokine production like TLR, causing their downregulation once vitamin D levels are restored. This implies a comprehensive role of vitamin D in IFN-α biosynthesis in human NK cells. DisclosuresStilgenbauer:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Hoffmann La-Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmcyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

EVALUATION OF VITAMIN D SERUM LEVELS IN PATIENTS WITH INSOMNIA

Objectives: The primary objective of the study was to evaluate the link existing between insomnia and low levels of Vitamin D and the secondary objective was to confirm a link between age and insomnia.Methods: The study assessed the Vitamin D serum levels in 50 subjects with insomnia (diagnosed using Pittsburgh Sleep Quality Index [PSQI]) from the outpatient clinic, Department of General Medicine of Sri Ramachandra Medical Center. All subjects fulfilled the eligibility criteria and also signed the informed consent form provided in patient’s native language for their convenience. With all aseptic precautions, 5 ml of blood was collected from the subjects for tyhe measurement of 25-OH Vitamin-D total levels using fully automated chemiluminescent immunoassay. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS 1 7.1). Quantitative variables will be expressed as mean ± standard deviation (SD), and qualitative variables will be expressed as percentage values.Results: All the patients who are insomniacs were deficient of Vitamin D. Of this, 80% were in deficient state (i.e.,&gt;20 ng/ml) and the rest 20% were in the insufficient state (i.e., 20–30 ng/ml). Most of the insomniacs were younger adults. As shown in the graph, 27 patients were in between the age group of 20 and 30 years, 13 patients of 50 patients were between 30 and 40 years of age, 4 patients between 40 and 50 years of age, 4 patients between 50 and 60 years of age, and 2 patients were of age between 60 and 70 years.Conclusion: Our results concluded that insomnia has a direct link with Vitamin D deficiency. Male insomniacs who were Vitamin D deficient were 40% more than female insomniacs with Vitamin D deficiency. It was noted that the incidence of increased body mass index and systolic blood pressure was seen among Vitamin D-deficient insomniacs. Insomnia was more prevalent among younger age groups rather than older adults. Global PSQI value evaluated among all Vitamin D-deficient patients was &gt;5, which indicated poor sleep quality.

Vitamin D Status in Pediatric Patients with Newly Diagnosed Malignant Disease: Preliminary Results

Objectives – Vitamin D (VD) has an impact on the immune system via vitamin D nuclear receptor (VDR) present in various types of immune cells. Its anti-angiogenic, pro-apoptotic, and anti-proliferative effect have been found as well. We investigated VD status of paediatric patients with malignant disease such as leukaemia, lymphoma, Langerhans cell histiocytosis, and solid malignant tumours. Materials and Methods – In children with malignant disease from the case cohort, total 41, serum VD level was measured upon first admission to the hospital. They were subdivided into those with leukaemia / lymphoma and those with solid malignant tumours (body and central nervous system). Langerhans cell histiocytosis was included in leukaemia /lymphoma group. The optimal level for VD was recommended to be >75 nmol/L. The insufficiency was presented with levels of 25-OH VD between 50 and 75 nmol/L, while levels ≤50 nmol/L were recognized as deficiency. We further categorized deficiency as strong (30 – 49.9 nmol/L), significant (20 – 29.9 nmol/L) and extreme (<20 nmol/L). Results – Only three patients had optimal level of VD. All others (92.8%) suffered from VD insufficiency 11 (26.8%) and various levels of deficiency: 10 (24.4%) from strong, 11 (26.8%) significant, and 6 (14.6%) from extreme. Conclusions – The prevalence of VD insufficiency/deficiency in paediatric patients with malignant disease is very high especially in patients with solid malignant tumour. Such condition, regarding that VD insufficiency/deficiency can debilitate immune system may have a negative impact on these patients.

Correlation between serum 25-hydroxyvitamin D3 and carpal tunnel syndrome in type 2 diabetes

Objective To investigate the relationship between serum 25-OH vitamin D3(25-OHD3)levels and carpal tunnel syndrome(CTS)in type 2 diabetes. Methods Data from 102 patients with type 2 diabetes were collected, and patients were divided into a CTS group(n=29)and a non-CTS group(n=73)according to clinical symptoms, signs, and electrophysiological testing.Fasting venous blood was collected to assay serum 25-OHD3 levels that were compared between the two groups.The correlation between 25-OHD3 and clinical parameters for type 2 diabetes was analyzed. Results The incidence of vitamin D3 deficiency was 65.5%(n=19)in the CTS group and 46.6%(n=34)in the non-CTS group, and the difference was statistically significant(χ2=16.85, P<0.01). Levels of 25-OHD3 were lower in the CTS group(14.13±4.91)μg/L than in the non-CTS group(17.08±3.35)μg/L(t=4.067, P<0.01). Levels of 25-OHD3 were negatively correlated with those of glycosylated hemoglobin(HbA1c)(r=-0.176, P=0.041)and the duration of diabetes(r=-0.29, P=0.01). Conclusions Low 25-OHD3 is a risk factor for carpal tunnel syndrome in type 2 diabetes and is negatively associated with the duration of diabetes and HbA1c in patients with type 2 diabetes. Key words: Diabetes mellitus, type 2; Vitamin D; Carpal tunnel syndrome

Mother\u2019s obesity and high child\u2019s waist circumference are predictive factors of severe child\u2019s obesity: an observational study in French Guiana

BackgroundThis study aims to describe the predictive factors of severe obesity in children followed in French Guiana.MethodsIn this observational study, the patients from the French Guianese Childhood Obesity Group database were prospectively included, after giving a statement of patient’s non opposition.ResultsOur group classifications revealed that 36 of 150 (24%) participants were classified as being metabolically abnormal obesity“ (MAO), while 114 of 150 (76%) were categorized as metabolically normal obesity” (MNO). MAO-patients were older. Their mothers had more severe obesity. We also observed that their systolic blood pressure was higher. The median Z-score BMI of children with MAO was 4, 9 [4, 05–5, 38], which shows a more obese condition than the MNO group. The median waist-to-height ratio (WTHR) of our study population was high, either 0.63 [0.54–0.59]. No significant differences in the term of pregnancy, father’s obesity, gender, birth weight, feeding, diastolic blood pressure and WTHR were found between the two groups. The predictors of MAO status, after adjusting for age and sex, were mother’s obesity and high child’s waist circumference.Among the comorbidity, there were two Down syndrome, one Cornelia de Lange syndrome, one Nephrotic Syndrome and one Epilepsy. The leptin hormone and insulin levels were higher in MAO than in MNO, while 25-OH D-vitamin was higher in MNO.ConclusionThis study indicates the need to incorporate waist circumference into routine clinical practice, in addition to traditional measures of weight, height, body mass index and waist-to-height ratio.

Rapid and reliable 25-OH vitamin D2 and 25-OH vitamin D3 measurements by multitasker LC-MS/MS

Rapid and reliable 25-OH vitamin D2 and 25-OH vitamin D3 measurements by multitasker LC-MS/MS

A monoclonal antibody sandwich ELISA for vitamin D-binding protein (VDBP) is unaffected by Gc-globulin phenotype peptides and actin and demonstrates reduced levels in sepsis and non-sepsis intensive care patients

The measurement of vitamin D-binding protein (VDBP) by immunoassay has been confounded by variable antibody recognition of the Gc1s, Gc1F and Gc2 phenotypes. This has led to spurious conclusions regarding vitamin D status in different ethnic groups. In order to overcome these problems there is a requirement for VDBP antibodies that are unaffected by phenotype status. Here we report the generation and testing of three monoclonal antibodies to VDBP which recognise linear epitopes and are unaffected by vast molar excesses of synthetic peptides spanning these phenotypic domains. These IgG1 kappa antibodies were purified and biotinylated to allow suitable pairings to develop a sandwich ELISA for circulating VDBP. The VDBP ELISA is unaffected by actin and confirms that VDBP levels are significantly reduced in sepsis patients and non-sepsis intensive care patients compared to normal healthy subjects. Levels of VDBP along with total 25OH vitamin D3 can be used to calculate free 25OH vitamin D3 levels and these compare well with consensus values determined independently. The VDBP ELISA meets acceptable performance criteria and as such can be used in conjunction with total 25OH vitamin D3 to determine the free 25OH vitamin D3 status in various cohorts.

The effect of seasonal variations on food consumption, dietary habits, anthropometric measurements and serum vitamin levels of University Students

Aim: The aim of this study was to examine the effect of seasonal variations on the dietary habits, food consumption, anthropometric measurements, physical activity and some serum vitamin levels of adult females. Methods:The study was conducted during consecutive four seasons in October (autumn), January (winter), April (spring), and July (summer). After general information was obtained about the participants via questionnaire, their anthropometric measurements were taken, and individual records kept for 7-day individual food consumption and 3-day physical activity. Also, their body compositions (Body Stat 1500O) and resting metabolic rates (Ergospirometry-Cosmed K4b2) were measured. Participant serum samples were analyzed for levels of vitamins A, E, β-carotene and 25-OH Vitamin D3. Subjects: Thirty-five healthy, young adult females between the ages of 19 and 24 were invited into a prospective research study. Results: Spring was found to be the season with the highest intake of energy and nutrients compared with other seasons (p 0.05). A significant positive correlation was determined between the levels of serum β-carotene and dietary β-carotene intake in autumn (r = 0.37, p<0.05). Conclusion: It was concluded that seasonal variations have significant effect on the nutritional status, body weights and compositions, daily energy expenditures, and particular serum vitamin levels in individuals. This should be taken into consideration when developing individual nutrition plans and establishing nutrition policies in Turkey, where all four seasons are experienced conspicuously.

Coexisting B- Cell Lymphoma and Benign Mesenchymal Phospaturic Tumor: Debut as Acute Renal Failure Associated with Hypercalcemia and Hypophosphatemia

The present case starts as an acute renal failure related to severe hypercalcemia, hypophosphatemia, increased FGF-23 and decreased TRP. All the previous are associated with increased bone exchange rate, low PTH, undetectable levels of PTH-RP, 1-25 OH Vitamin D3 in upper level of normal range and bone densitometry compatible with osteoporosis in trabecular bone. These results seem compatible with an increase in bone resorption, urinary loss of calcium and phosphate, and none induced by PTH. Complementary studies suggest the spleen is the organ directly related with this case. In conclusion, a B Cell Lymphoma was diagnosed. It explained the causes of the hypercalcemia, either by the effect of a lymphotoxin, TNF or interleukin 1. After total remission of the lymphoma, the hypophosphatemia persisted, as did the Hight levels of FGF-23, low levels of TPR and a pathological bone densitometry. This lead us to believe in the presence of a phosphatizing producer tumor located in the spleen. Once the splenectomy was done, the analytical findings returned to normal and the histologic evidence confirmed the initial clinical prediction.

Study of bone mineral density and their determinants among Medical practitioners of a Tertiary care Government hospital

Background Vitamin D deficiency prevails in epidemic proportions all over the Indian subcontinent with a prevalence of 70ndash100 in the general population. Hence it is important to estimate its burden in doctors and other health care providers.Objectives 1. To test Bone Mineral Density BMD values using Dual Energy X-Ray Absorptiometry DEXA scan among the study population. 2. To correlate values of Bone Mineral Density with serum 25-OH cholecalciferol serum calcium weight height body mass index BMI sun exposure physical activity and diet. 3. To document known co-morbidities among study population.Methodology The study is a prospective cross sectional study.50 medical practitioners adhering to the inclusion and exclusion criteria of the study were invited for participation with voluntary consent. Their Bone Mineral Density values were calibrated by using an Ultrasound based Bone mineral densitometer having a 1 MHz transducer probe. Serum Vitamin D values were estimated by radioimmunoassay method and were expressed in nmolL. Serum Calcium values were estimated by semiauto-analyzer.Results 58 of study population had normal bone mineral density. Only 12 had normal serum vitamin D. There was no significant association between bone mineral density and serum VitaminD. Conclusion The Bone Mineral Density BMD values in the study population are on an average in the osteopenic range with low serum vitamin D levels.

Preoperative Vitamin D levels and respiratory complications of general anesthesia.

This research aims to investigate whether there is a correlation between the respiratory complications occurring in patients under general anesthesia and preoperative Vitamin D levels. The study was a prospective observational study. This study included 95 adult cases. The cases had total 25-hydroxyvitamin D (25OHD) levels identified in blood samples before the operation. Patients given routine general anesthesia and were assessed in terms of respiratory complications during anesthesia induction, extubation, anesthesia recovery, and the first 24-h postoperative. The Shapiro-Wilk test, Student's-t-test, one-way ANOVA test, Pearson correlation coefficient, and Chi-square tests were used. The mean 25OHD vitamin level identified in the preoperative period was 13.00 ± 6.57 ng/mL, with 25OHD vitamin levels found to be significantly low in female cases compared to male cases (P < 0.05). There was a statistically significant negative relationship between age and 25OHD vitamin levels identified (P = 0.045). When assessed in terms of surgery types, there was no significant difference found in Vitamin D levels in terms of surgery type. When examined for complications in the induction, extubation period, and postoperative recovery period, there was a significant difference identified between 25OHD vitamin levels and these complications (P < 0.01). This research observed that patients with low preoperative 25OHD vitamin levels encountered respiratory complications related to general anesthesia more often. Especially, in the early postoperative period, there is a very significant difference between complications and low 25OHD vitamin levels.

Vitamin D status in children with headache: A case-control study

Vitamin D is a fat soluble vitamin with hormonal properties, plays crucial functions in bone and mineral metabolism and has important regulatory functions in brain development, cell differentiation and apoptosis. Some studies have shown a link between vitamin D deficiency and headache. In this study, 147 patients with headache (migraine or either tension-type headache (TTH)) and 69 healthy controls, aged 5 to 16 years, were evaluated. Each group was also divided into two separate sub-groups based on presentation to the clinic in either high solar-exposure (HSE) and low solar-exposure (LSE).We retrospectively evaluated the levels of calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and 25-OH vitamin-D3. Levels below 20ng/ml were described as vitamin D deficiency and levels of 2030ng/ml as vitamin D insufficiency. The levels of 25-OH vitamin-D3 were statistically significantly lower when compared to the control group (17.1±9.4 vs. 25.8±12.8ng/mL, respectively; p<0.001). This held true for both the HSE and LSE group compared to the control group (for the group 1; 24.6±11.8 vs. 32.1±10.6ng/mL, respectively; p=0.007, and for the group 2; 14.5±6.8 vs. 19.6±13.5ng/mL, respectively; p=0.003). Also in headache subgroups (migraine and TTH), vitamin D levels were significantly lower than the control group (17.3±9.0, 16.9±9.9 and 25.8±12.8ng/mL respectively; p<0.001). There may be a relationship between vitamin D deficiency and headache, with particular significance in LSE. We suggest that this conclusion needs to be supported with randomised clinical studies containing a larger numbers of samples and controls.

Relationship of bone density with serum parathyroid hormone in hemodialysis patients; a single center study

Introduction: The existence of a relationship between the level of serum parathyroid hormone (PTH) and bone density can be a warning sign in hemodialysis patients. Objectives: In the studies conducted so far, the relationship between these two factors has not been specifically investigated. Hence, this study was aimed to exclusively evaluate the levels of serum PTH hormone and bone density. Patients and Methods: In this cross sectional study, 85 eligible chronic hemodialysis patients aged over 18 years old, who had underwent hemodialysis a minimum of two times a week for at least six months were enrolled in the study. Serum intact PTH, 25 OH-vitamin D3, CBC-calcium, phosphorus, alkaline phosphatase, albumin, and VBG were measured. Additionally, lumbar radiographic profile and densitometry tests were conducted for patients. Results: The mean age of patients was 52.9 years (20 to 86 years old). Of them, 43 patients were male (50.6%). There was a significant correlation between age and the decrease in bone density (p =0.004). There was a significant relationship between different groups of bone density and serum vitamin D3 level (P < 0.05). Based on the results of Z standard, a significant difference between the mean levels of intact PTH in different groups of bone density was seen (p = 0.037). Conclusion: The prevalence of osteopenia and osteoporosis in hemodialysis patients is high. In addition, the decrease in bone density is associated with high levels of parathyroid hormone. While, this association is mainly associated with Z score, it is necessary to investigate the secondary causes of this condition.

Selective blood sampling for FGF-23 in tumor-induced osteomalacia.

Tumor-induced osteomalacia (TIO) is caused by the hormone fibroblast growth factor 23 (FGF-23). It is mainly produced in the tissue of mesenchymal tumors. Patients with TIO frequently suffer from a chronic decompensated pain syndrome and/or muscle weakness with postural deformity. Despite the severity of the disease, the diagnosis is frequently established late. In some cases, it takes several years to establish the condition. This case report concerning a 68-year old woman demonstrates the selective blood sampling for FGF-23 as path-breaking diagnostics to confirm the diagnosis of a neuroendocrine tumor.Learning points:Tumor-induced osteomalacia is a rare condition compared to other paraneoplastic syndromes.It causes complex symptoms such as progressive reduction of physical capacity, exhaustion, fatigue, a decompensated pain syndrome of the musculoskeletal system and fractures of several bones.Elevated serum levels of FGF-23 implicate massive phosphate elimination and resulting hypophosphatemia.The diagnosis is often established over a period of several years because the localization of small FGF-23-producing tumors is complicated.It is the combination of MRI and selective blood sampling for FGF-23 which permits reliable identification of tumors causing TIO and leads to accurate localization.In a patient with generalized pain and reduced physical capacity, osteological parameters such as phosphate, 25-OH vitamin D3 and 1,25-(OH)2D3, as well as bone-specific alkaline phosphatase levels in serum should be determined. Hypophosphatemia should always lead to further diagnostic investigations aiming at the detection of an FGF-23-producing tumor.

Screening for celiac disease in poorly controlled type 2 diabetes mellitus: worth it or not?

BackgroundRecent studies have demonstrated that immune factors might have a role in the pathophysiology of insulin resistance and type 2 diabetes mellitus (T2DM). Inappropriate glycemic control in patients with T2DM is an important risk factor for the occurrence of diabetes complications. The prevalence of celiac disease (CD) is high in type 1 diabetes mellitus however, there are scarce data about its prevalence in T2DM. Our aim was to investigate the prevalence of celiac disease among insulin-using type 2 diabetes patients with inappropriate glycemic control.MethodsIgA tissue transglutaminase antibodies (tTGA IgA) test was performed as a screening test. A total of 135 patients with T2DM whose control of glycemia is inappropriate (HbAlc value >7%) in spite of using insulin treatment for at least 3-months (only insulin or insulin with oral antidiabetic drugs) and 115 healthy controls were enrolled in the study. Upper gastrointestinal endoscopy with duodenal biopsy was performed to all patients with raised tTGA IgA or selective lgA deficiency.ResultsGender, age, body mass index (BMI) and tTGA IgA, kreatinin, calcium, LDL-cholesterol (LDL-C), total cholesterol, 25-OH vitamin D3 levels were similar between groups. Systolic and diastolic blood pressure, waist circumference, fasting plasma glucose, postprandial plasma glucose, urea, sodium, HbA1c, LDL-C, triglyceride, vitamin B12 levels were significantly higher in DM group (p < 0.0001). BMI, high-sensitive CRP, microalbuminuria, and AST, ALT, potassium, phosphorus levels were significantly higher in the T2DM group (p < 0.05). HDL-cholesterol and parathormone levels were significantly lower in the T2DM group (p < 0.05). Two of the 135 patients with T2DM were diagnosed with CD (1.45%).ConclusionsThe prevalence of celiac disease among patients with type 2 diabetes, with poor glycemic control despite insulin therapy, is slightly higher than the actual CD prevalence in general population. Type 2 diabetic patients with inappropriate control of glycemia in spite of insulin treatment might be additionally tested for Celiac disease especially if they have low C-peptide levels.

Association of 25-OH Cholecalciferol with Acute Myocardial Infarction

In addition to its well known role on mineral homeostasis, vitamin-D has many diverse actions including anti-inflammatory, relaxation of vascular smooth muscle cells and downregulation of renal renin production. Deficiency of Vitamin-D is a treatable condition that has been found to be associated with coronary artery disease. This study was carried out to assess the vitamin-D status in acute myocardial infarction (AMI) patients. Active form of vitamin-D (1, 25-OH D3, calcitriol) does not reflect vitamin-D status due to its short plasma half life. 25-OH D3 or calcidiol is considered as circulating reservoir and is used to assess vitamin-D status due to its long plasma half life. In this study 25-hydroxycholecalciferol [25 (OH)D3] was assessed in 40 acute myocardial infarction patients and 40 age- and sexmatched healthy subjects. Serum 25-hydroxycholecalciferol and Lipid profile parameters were estimated. Data were analyzed with the help of SPSS version 20.0. Vitamin-D was found to be significantly reduced in AMI patients when compared with that of Controls which were 28.50±16.68 ng/l in cases and 38.32±16.47 ng/l in Controls, p=0.011. Blood pressure, total Cholesterol and LDL-Cholesterol were found significantly higher in AMI compared to those among healthy controls. Among all study subjects, statistically significant positive correlation of 25(OH)D3 was found with HDL-C (p=0.014). Significant negative correlation was found with serum TC (p=0.001) and LDL-C (p &lt;0.001). Serum TG was found negatively correlated with 25-hydroxycholecalciferol but it was not statitiscaly significant (p=0.068). In our study Vitamin-D deficiency was found to be significantly associated with myocardial infarction, dyslipidemia and hypertension.Bangladesh J Med Biochem 2015; 8(2): 55-59

Refining Long-Term Prediction of Cardiovascular Risk in Diabetes \u2013 The VILDIA Score

Cardiovascular risk assessment in patients with diabetes relies on traditional risk factors. However, numerous novel biomarkers have been found to be independent predictors of cardiovascular disease, which might significantly improve risk prediction in diabetic patients. We aimed to improve prediction of cardiovascular risk in diabetic patients by investigating 135 evolving biomarkers. Based on selected biomarkers a clinically applicable prediction algorithm for long-term cardiovascular mortality was designed. We prospectively enrolled 864 diabetic patients of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study with a median follow-up of 9.6 years. Independent risk factors were selected using bootstrapping based on a Cox regression analysis. The following seven variables were selected for the final multivariate model: NT-proBNP, age, male sex, renin, diabetes duration, Lp-PLA2 and 25-OH vitamin D3. The risk score based on the aforementioned variables demonstrated an excellent discriminatory power for 10-year cardiovascular survival with a C-statistic of 0.76 (P < 0.001), which was significantly better than the established UKPDS risk engine (C-statistic = 0.64, P < 0.001). Net reclassification confirmed a significant improvement of individual risk prediction by 22% (95% confidence interval: 14–30%) compared to the UKPDS risk engine (P < 0.001). The VILDIA score based on traditional cardiovascular risk factors and reinforced with novel biomarkers outperforms previous risk algorithms.

Counter-intuitive plasma vitamin D and zinc status in HIV-1-infected adults with persistent low-level viraemia after treatment initiation: a pilot case-control study.

Determinants of persistent low-level viraemia [PLLV, a viral load (VL) of between 50 and 500 copies/mL] have not been elucidated. In a case-control study, we evaluated the influence of micronutrients on PLLV in a population of 454 HIV-1 adults having initiated antiretroviral therapy (ART) between January 2007 and December 2011. Plasma levels of retinol (vitamin A), 25-OH vitamin D2+D3, vitamin E and zinc were measured at ART initiation in cases (PLLV after 6months of ART) and in controls (VL <50 copies/mL after 6months). Cases and controls were matched for the CD4 cell count (±50/mm3) and ethnic origin. Intergroup differences in demographic, biological and treatment parameters and sunshine intensity at ART initiation were adjusted using a propensity score. A receiver operating characteristic (ROC) curve was used to assess intergroup differences in plasma micronutrient levels. Thirty-three of the 454 patients (7.3%) displayed PLLV (median VL: 92 copies/mL). Patients were predominantly male (89%), Caucasian (64%) and CDC stage C (25%). The median age was 38 years, the median initial VL was 5.2 log10 copies/mL and the median CD4 count was 74/mm3. The 22 cases and matched controls were balanced in these respects, and had similar vitamin A/E levels. Two cases (9%) and 9 controls (41%) had a vitamin D level<10.3ng/mL (p=0.0015), and 2 cases (9%) and 10 controls (48%) had a zinc level<74.6μg/dL (p=0.04). Our results support in vitro studies suggesting that vitamin D favours HIV-1 replication and that HIV-1 is zinc-dependent. Wide-scale, prospective studies are required.

A phase II RCT of high-dose vitamin D supplementation for androgen deprivation therapy (ADT)-induced bone loss among older prostate cancer (PCa) patients.

10113 Background: ADT is the most commonly used systemic therapy for treating locally advanced and metastatic PCa. ADT use causes hypogonadism, which can result in accelerated bone loss and fragility fractures. Vitamin D (VITD) may protect against bone loss; however it remains unclear if the recommended daily allowance (RDA) of VITD is sufficient to reduce bone loss or whether higher doses are needed. The aim of this phase II RCT was to collect preliminary data on the effect of high-dose VITD on bone mineral density (BMD) in ADT-treated PCa patients compared to the RDA of VITD. Methods: Older PCa patients (≥60 years old) with VITD insufficiency ( &lt; 32 ng/ml), within 6 months of starting ADT and with 6 more planned months of ADT were randomized 1:1 to high-dose VITD (hVITD; 600 IU/daily plus 50,000 IU/weekly) or RDA of VITD (rVITD; 600 IU/daily plus placebo weekly) for 24 weeks. All subjects received 100% of the RDA for calcium (1,000 mg/day). BMD was assessed at the total hip (TH) and lumbar spine (LS) via DXA at pre- and post-intervention. ANCOVA was used to test the change in BMD between groups. Results: 59 PCa patients were accrued (85% white; mean age = 67.6). Serum analyses confirmed high compliance in both groups (25-OH VITD change: hVITD = +32.0 ng/ml vs rVITD = +4.3 ng/ml; p &lt; 0.01). The safety of hVITD was similar to rVITD (Grade I hypercalcemia: hVITD: n = 1 vs rVITD: n = 0). Bone loss was significantly reduced for the hVITD group compared to rVITD group for total hip (TH BMD% change: hVITD = −1.5% vs rVITD = −4.1%; p = 0.02), with a trend for the femoral neck (BMD% change: hVITD = −1.7% vs rVITD = −4.3%; p = 0.06) and trochanter (BMD% change: hVITD = −1.0% vs rVITD = −2.8%; p = 0.10). There was no difference between groups for LS bone loss (LS BMD% change: hVITD = −0.8% vs rVITD = −0.6%; p = 0.75). Conclusions: High-dose VITD supplementation produced significantly greater reductions in hip BMD loss among older PCa patients receiving ADT compared to rVITD. Clinically, higher doses of VITD may be necessary to effectively prevent ADT-induced bone loss. A definitive phase III RCT is needed to confirm these findings. Funding: NCI R21CA175793, K07CA168911 &amp; UG1CA189961. Bio-Tech Pharmacal Inc. supplied all agents. Clinical trial information: NCT02064946.

Investigation of total and free 25OHD vitamin levels in patients with chronic renal failure on different dose of cholecalciferol

Investigation of total and free 25OHD vitamin levels in patients with chronic renal failure on different dose of cholecalciferol