Effects Of Vitamin D3 Treatment Research Articles

Expression of phosphate and calcium transporters and their regulators in parotid glands of mice

The concentration of inorganic phosphate (Pi) in plasma is under hormonal control, with deviations from normal values promptly corrected to avoid hyper- or hypophosphatemia. Major regulators include parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23), and active vitamin D3 (calcitriol). This control is achieved by mechanisms largely dependent on regulating intestinal absorption and renal excretion, whose combined actions stabilise plasma Pi levels at around 1–2 mM. Instead, Pi concentrations up to 13 and 40 mM have been measured in saliva from humans and ruminants, respectively, suggesting that salivary glands have the capacity to concentrate Pi. Here we analysed the transcriptome of parotid glands, ileum, and kidneys of mice, to investigate their potential differences regarding the expression of genes responsible for epithelial transport of Pi as well as their known regulators. Given that Pi and Ca2+ homeostasis are tightly connected, the expression of genes involved in Ca2+ homeostasis was also included. In addition, we studied the effect of vitamin D3 treatment on the expression of Pi and Ca2+ regulating genes in the three major salivary glands. We found that parotid glands are equipped preferentially with Slc20 rather than with Slc34 Na+/Pi cotransporters, are suited to transport Ca2+ through the transcellular and paracellular route and are potential targets for PTH and vitamin D3 regulation.

Effect of Vitamin D3 Treatment on Genes Expression of Corticotrophin Releasing Hormone (CRH), CRH Receptor 1 (CRH-R1) and Connexin-43 (CON-43) in PHM1-41 Cell Line that Induced by Hypoxia

Introduction: Hypothalamic-Pituitary-Adrenal (HPA) axis activity is one of pathophysiologic mechanism that caused preterm labor. Biologic maternal stress, for instance hypoxia condition, is one of the causes that can trigger preterm birth occasion through the activation of HPA axis. It increases Corticotrophin Releasing Hormone (CRH), CRH receptor 1 (CRH-R1), and Connexin-43 (CON-43) as the trigger of the contraction process. Vitamin D as a source of Ca2+ ion is needed for myometrium smooth muscle’s concentrations and relaxation mechanism. The aim of this study was to determine the effect of vitamin D3 in PHM1-41 cell line. Materials and Methods: The human smooth muscle uterine myometrium cell line PHM1-41 as an in vitro model experimental subject, treated by hypoxia oxidative stress condition and added by vitamin D3 (5, 10, 50 and 150 nM). The dichlorodihydrofluorescein diacetate (DCFDA) fluorescent was used to measure the level of intracellular reactive oxygen species (ROS). In addition, RNA of treated PHM1-41cells was isolated for analyzing gene expressions such as CRH, CRH-R1, and CON-43 as a profile of contractility regulation. Results: ROS level effectively decrease in the cells that treated by 150 nM vitamin D3 group compared to the control hypoxia cell group (7.16 ± 0.23 and 19.49 ± 1.76, respectively). Expression of CRH, CRH-R1, and CON-43 genes are also decrease by treated with 150 nM vitamin D3 to the cells. Pearson (parametric) correlation analysis evidenced a negative correlation between the vitamin D3 additional treated to the lower of ROS level, CRH, CRH-R1, and CON-43 genes expression on PHM1-41 cell line that induced by oxidative stress condition. Conclusion: The concentration of 150 nM vitamin D3 was a prominent potency to prevent the incidence of preterm labor.
 HIGHLIGHTS
 
 Hypothalamic-Pituitary-Adrenal (HPA) axis is one of the causes of preterm birth that marked by high level of intracellular ROS leads to increasing of Corticotrophin Releasing Hormone (CRH) which has significant role in aterm and preterm labor
 PHMI-41 cells can describe the Corticotrophin Releasing Hormone (CRH), CRH receptor 1 (CRH-R1), and Connexin-43 (CON-43) genes expression level so it was used as model of human pregnancy condition
 Vitamin D3 is one of antioxidant agent that can decrease ROS level also CRH, CRH-R1, and CON-43 genes expression on PHM1-41 cell especially at doses of 150 nM which shown a prominent potency to prevent the preterm labor incidence
 
 GRAPHICAL ABSTRACT

Sex-Specific Catabolic Metabolism Alterations in the Critically Ill following High Dose Vitamin D.

Pharmacological interventions are essential for the treatment and management of critical illness. Although women comprise a large proportion of the critically ill, sex-specific pharmacological properties are poorly described in critical care. The sex-specific effects of vitamin D3 treatment in the critically ill are not known. Therefore, we performed a metabolomics cohort study with 1215 plasma samples from 428 patients from the VITdAL-ICU trial to study sex-specific differences in the metabolic response to critical illness following high-dose oral vitamin D3 intervention. In women, despite the dose of vitamin D3 being higher, pharmacokinetics demonstrated a lower extent of vitamin D3 absorption compared to men. Metabolic response to high-dose oral vitamin D3 is sex-specific. Sex-stratified individual metabolite associations with elevations in 25(OH)D following intervention showed female-specific positive associations in long-chain acylcarnitines and male-specific positive associations in free fatty acids. In subjects who responded to vitamin D3 intervention, significant negative associations were observed in short-chain acylcarnitines and branched chain amino acid metabolites in women as compared to men. Acylcarnitines and branched chain amino acids are reflective of fatty acid B oxidation, and bioenergesis may represent notable metabolic signatures of the sex-specific response to vitamin D. Demonstrating sex-specific pharmacometabolomics differences following intervention is an important movement towards the understanding of personalized medicine.

Impact of Vitamin D Deficiency on the Pathogenesis of Polycystic Ovary Syndrome

There are many metabolic and hormonal factors related to polycystic ovary syndrome (PCOS) that can be affected by vitamin D3 supplementation. To find clinical trials, in vivo studies, and in vitro studies that met the review's inclusion and exclusion criteria, we searched many databases. PCOS women's ovulation and metabolic parameters were examined in relation to the effects of vitamin D3 treatment on PCOS risk variables such as seasonal changes in body mass index, and obesity. The current review included twenty-five articles. Vitamin D3(25-hydroxy vitamin D) levels were significantly lower in the PCOS group than in the control group, and lipid profile and androgen hormone levels were significantly higher in the PCOS group, resulting in increased cardiovascular events and exaggerated hirsutism. According to the majority of research, vitamin D3 plays a beneficial role in decreasing the pathophysiology of PCOS, notably in restoring ovulation, which ultimately improves fertility. Although other studies found no effect on lipid profile, there was a minor effect on reducing cardiovascular risks. The response of patients to vitamin D3 was influenced by the dose administered and the study's methodology. In conclusion, vitamin D3 had a good effect on the pathophysiology of PCOS in the majority of investigations.

Vitamin D3 Prevents the Deleterious Effects of Testicular Torsion on Testis by Targeting miRNA-145 and ADAM17: In Silico and In Vivo Study.

Testicular torsion (TT) is the most common urological emergency in children and young adults that can lead to infertility in many cases. The ischemia-reperfusion (IR) injury due to TT has been implicated in the pathogenesis of testicular damage. The main pathological mechanisms of contralateral injury after ipsilateral TT are not fully understood. In the presented study, we investigated the molecular and microscopic basis of ipsilateral and contralateral testicular injury following ipsilateral testicular torsion detorsion (T/D) and explored the possible protective role of vitamin D3. The biochemical analysis indicated that IR injury following T/D significantly decreased the activity of testicular glutathione peroxidase (GPx) enzyme, level of serum testosterone, serum inhibin B, and expression of testicular miRNA145, while increased the activity of testicular myeloperoxidase (MPO) enzyme, level of testicular malondialdehyde (MDA), level of serum antisperm-antibody (AsAb), and expression of ADAM-17. The histological and semen analysis revealed that torsion of the testis caused damages on different tissues in testis. Interestingly, administration of vitamin D3 prior to the IR injury reversed the deterioration effect of IR injury on the testicular tissues as indicated by biochemical and histological analysis which revealed normal appearance of the seminiferous tubules with an apparent decrease in collagen fiber deposition in both ipsilateral and contralateral testes. Our results revealed that the protective effect of vitamin D3 treatment could be attributed to target miRNA145 and ADAM17 protein. To further investigate these findings, we performed a detailed molecular modelling study in order to explore the binding affinity of vitamin D3 toward ADAM17 protein. Our results revealed that vitamin D3 has the ability to bind to the active site of ADAM17 protein via a set of hydrophobic and hydrophilic interactions with high docking score. In conclusion, this study highlights the protective pharmacological application of vitamin D3 to ameliorate the damages of testicular T/D on the testicular tissues via targeting miRNA145 and ADAM17 protein.

Vitamin D3 Attenuates Viral-Induced Inflammation and Fibrotic Responses in Bronchial Smooth Muscle Cells.

Toll-like receptor 3 (TLR3) activation by viral infections plays a key role in promoting inflammatory immune responses that contribute to pulmonary fibrosis in chronic inflammatory respiratory diseases. Vitamin D3 has been shown to be beneficial to patients with asthma and chronic obstructive pulmonary disease (COPD) through its anti-inflammatory and anti-fibrotic properties. Smooth muscle cells are one of the major contributors to airway remodeling in asthma and COPD. We therefore aimed to investigate the effect of vitamin D3 treatment on viral-induced TLR3 responses in Bronchial Smooth Muscle Cells (BSMCs) as a mechanism contributing to pulmonary fibrosis in asthma and COPD. Primary BSMCs from patients with asthma (n=4), COPD (n=4), and healthy control subjects (n=6) were treated with polyinosinic: polycytidylic acid (polyI:C), TLR3 agonist in the presence or absence of vitamin D3 (1,25D3). Here we report the mRNA expression and protein levels of pro-inflammatory and pro-fibrotic markers (IL-6, IFN-β1, CCL2/MCP-1, fibronectin 1 and type I collagen) among BSMCs groups: asthma, COPD, and healthy controls. We show that at the baseline, prior to polyI:C stimulation, asthma and COPD BSMCs presented increased pro-inflammatory and pro-fibrotic state compared to healthy control subjects, as measured by quantitative PCR and immunoassays (ELISA/Flow Cytometry. Ligation of TLR3 by polyI:C in BSMCs was associated with increased TLR3 mRNA expression, and 1,25D3 treatment significantly reduced its expression. In addition, 1,25D3 decreased the expression of IL-6, IFN-β1, CCL2, FN1 and COL1A1 induced by polyI:C in BSMCs. The regulatory effect of 1,25D3 treatment on polyI:C-stimulated BSMCs was further confirmed at protein levels. Our findings suggest that vitamin D3 attenuates TLR3 agonist-induced inflammatory and fibrotic responses in BSMCs and support the clinical relevance of vitamin D3 supplementation in patients with viral infections having chronic respiratory diseases, such as asthma and COPD.

Vitamin D Receptor (VDR) Allelic Variants Correlating with Response to Vitamin D3 Supplementation in Breast Cancer Survivors

We investigated how vitamin D receptor (VDR) allelic variants affect breast cancer survivors’ responses to vitamin D3 supplementation to increase circulating 25-hydroxy vitamin D (25(OH)D) levels. Two hundred and fourteen patients who were diagnosed with breast cancer at least 6 mo, prior to the study and had completed all treatment regimens were assigned to consume 4000 IU of vitamin D3 daily for 12 weeks. Linear and multinomial logistic regression analyses were used to analyze the association of VDR single nucleotide polymorphism (SNPs) with changes in circulating 25(OH)D. The TaqI and BsmI VDR sequence variants modified the effect of vitamin D3 treatment on the plasma 25(OH)D changes (P value = 0.008 for TaqI and P value = 0.0005 for BsmI). Patients with the bb [Q4 vs. Q1 odds ratio(OR) 8.04, 95% confidence interval (CI) 1.55–41.57] and tt [Q4 vs. Q1 OR 4.64 95%CI 1.02–21.02] genotype of BsmI and TaqI had larger increases in plasma 25(OH)D levels compared to those with BB and TT genotype respectively after adjustment for potential confounders. Haplotype analyses suggested the existence of specific combination of alleles that might be associated with circulating 25(OH)D changes. VDR allelic variants modulate vitamin D3 supplementation to increase plasma 25(OH) levels in breast cancer survivors.

VITAMIN D3 ADMINISTRATION BEFORE AND AFTER DETORSION COULD SALVAGE THE TESTICULAR ENDOCRINE FUNCTION IN AN EXPERIMENTAL MODEL OF TESTICULAR TORSION/DETORTION

Background: Testicular torsion is one of the emergencies affecting mostly adolescent males, resulting in sub-fertility if notrapidly and efficiently managed. Oxidative stress, inflammatory response as well as immunological reactions were implicated in its pathogenesis. Recently interest in studying the non-skeletal effects of vitamin D is growing, many researches indicates its antioxidant, antiinflammatory and immuno-modulatory effects. Aim of the Work: Investigating the possible conservative effect of vitamin D3 treatment on testicular endocrinal function in testicular torsion/detorsion rat model, and elucidating its possible underlying mechanism. Materials and Methods: 24 young adult male albino rats,weighing 120-160 g., were randomly allocated into 3 groups, 8 in each group, Sham operated (SHAM), Testicular torsion/detorsion (T/D) and Testicular torsion/detorsion; vitamin D3 treated (T/D; D3) groups. All rats were subjected to measurement of absolute and relative testicular weight (ATW and RTW, respectively), assessment of testicular endocrinal function by serum total testosterone and inhibin B levels. In addition to determination of serum antisperm antibody(AsAb). Testicular tissue was examined for oxidative stress markers; malondialdeyde (T. MDA) and glutathione peroxidase (T, GPx), as well as inflammatory marker; myeloperoxidase (T. MPO). Results: Testicular T/D resulted in significant reduction in ATW, RTW, serum testosterone and inhibin B levels with significant elevation in serum AsAb, T. MDA and T. MPO when compared with SHAM group. On treatment with vitamin D3, RTW was significantly increased as compared with T/D group but still significantly less than SHAM group. Serum testosterone level was significantly increased when compared with both SHAM and T/D groups. Inhibin B was significantly increased as compared with T/D group but still notnormalized as being significantly less than SHAM group. Serum AsAb, T. MDA and T. MPO were significantly decreased when compared with T/D group, being normalized for T. MDA but still significantly higher for serum AsAb and T. MPO when compared with SHAM group, however, T. GPx was significantly increased as compared with both SHAM and T/D groups.Conclusion: Vitamin D3 could retrieve the testicular endocrinal dysfunction induced by Torsion/Detorsion by its antioxidant, antiinflammatory and immuno-modulatory effects.

Effects of Vitamin D3 on asymmetric- and symmetric dimethylarginine in arterial hypertension

Background and aimsAccumulating evidence has proposed a correlation between vitamin D (25(OH)D) insufficiency and cardiovascular (CV) disease. Vitamin D associated effects on endothelial function have been suggested to be a possible culprit. The present study investigated the association of vitamin D3 treatment on markers of endothelial dysfunction in patients with arterial hypertension. Methods and resultsThe Styrian Vitamin D Hypertension Trial is a double-blind, placebo-controlled, single-centre study conducted at the Medical University of Graz, Austria. A total of 200 study participants with arterial hypertension and 25(OH)D levels below 30ng/mL were enrolled. The study participants were randomized to receive 2800 IU of vitamin D3 per day as oily drops (n=100) or placebo (n=100) for a duration of eight weeks. The present study uses an analysis of covariance (ANCOVA) to investigate the effect of vitamin D3 treatment on symmetric (SDMA) and asymmetric dimethylarginine (ADMA). A total of 187 participants (mean [SD] age 60.0 [11.3] years; 47% women; 25(OH)D 21.2 [5.6]ng/mL; mean systolic blood pressure of 131.4 [8.9] mmHg on a median of 2 antihypertensive drugs) completed the trial. Mean treatment effect was −0.004 (95%CI [−0.03 to 0.04]; P=0.819) on ADMA and 0.001 (95%CI [−0.05 to 0.05]; P=0.850) on SDMA. In the subgroup analysis patients with a 25(OH)D concentration <20ng/mL had a significant increase in their log l-arginine/ADMA ratio (mean treatment effect 18.4 95%CI [1.84–34.9]μmol/L/μmol/L; P=0.030). ClinicalTrials.gov Identifier: NCT02136771 EudraCT number: 2009-018125-70 ConclusionsVitamin D3 supplementation in hypertensive patients with low 25-hydroxyvitamin D has no significant effect on ADMA and SDMA.

Abstract 4584: VDR genotype modifies vitamin D efficacy for colorectal adenoma prevention in a randomized controlled trial

Abstract Objective: Although epidemiological and pre-clinical research suggests that vitamin D and calcium supplementation reduce colorectal carcinogenesis, we found that they had no effect on risk of colorectal adenoma recurrence in a recently completed randomized controlled trial (Vitamin D/Calcium Polyp Prevention Study, NCT00153816). We now examine whether the effect of supplementation may be modified by common genetic variants in vitamin D and calcium pathway genes previously associated with 25-hydroxyvitamin D levels or other health outcomes. Methods: 41 candidate single nucleotide polymorphisms (SNPs) in 7 genes (GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, VDR and CASR) were genotyped in non-Hispanic white trial participants (N = 1,676). All had at least one adenoma at a baseline colonoscopy and were randomized to treatment with vitamin D3 (1000 IU/day), calcium (1200 mg/day), both or placebo in a modified 2×2 factorial design. Participants were followed until a subsequent colonoscopy 3 or 5 years later and assessed for the presence of at least one adenoma or advanced adenoma (adenoma ≥1 cm, or with &amp;gt;25% villous histology and/or high-grade dysplasia, or cancer). Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were used to estimate genotype effects, treatment effects and interactions. To account for multiple testing, based on the effective number of independent SNPs, statistical significance was defined as p&amp;lt;0.002. Results: VDR SNP rs731236 (Taq1, minor allele frequency 0.39) statistically significantly modified the effect of vitamin D3 treatment on advanced adenomas (interaction RR = 0.49, 95% CI = 0.31-0.76, P = 0.001) but not on any adenoma (interaction RR = 0.94, 95% CI = 0.80-1.11, P = 0.48). Among participants (N = 249, 15%) with the homozygous variant genotype, the risk of an advanced adenoma was 15.2% among those randomized to placebo, and 3.2% among those randomized to vitamin D; a risk reduction of 78% for vitamin D supplementation (RR = 0.22, 95% CI = 0.08-0.63, P = 0.005). In contrast, among participants with one or more wild type allele (N = 1400, 85%), the risk of an advanced adenoma was 8.8% among those randomized to placebo, and 10.5% among those randomized to vitamin D; an apparent risk increase of 19% for vitamin D supplementation (RR = 1.19, 95% CI = 0.86-1.64, P = 0.3). Several other VDR SNPs in linkage disequilibrium with rs731236 had borderline statistically significant interactions. However, there were only nominally statistically significant (P&amp;lt;0.05) interactions of SNP genotypes with calcium treatment on adenoma outcomes. Conclusions: Our results suggest that the effect of vitamin D3 supplementation on colorectal carcinogenesis depends on common genetic variants in VDR, with a 78% reduction in risk of advanced adenomas in individuals with the rs731236 homozygous variant genotype, and no benefit in individuals with one or more wild type alleles. Note: This abstract was not presented at the meeting. Citation Format: Elizabeth L. Barry, Leila A. Mott, Judith R. Rees, Dennis J. Ahnen, Roberd M. Bostick, Robert S. Bresalier, Douglas J. Robertson, Robert W. Summers, John A. Baron. VDR genotype modifies vitamin D efficacy for colorectal adenoma prevention in a randomized controlled trial. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4584. doi:10.1158/1538-7445.AM2015-4584

Serum sclerostin is decreased following vitamin D treatment in young vitamin D-deficient female adults

Sclerostin is produced almost exclusively by osteocytes, which also express receptors for 1,25 dihydroxyvitamin D3. The aim of this study was to investigate the effects of vitamin D3 treatment on serum sclerostin levels in young adult females with severe vitamin D deficiency. A total of 26 subjects were treated orally with calcium (1.200mg/day for 2months) and vitamin D3 (300.000IU/week for 1month). Serum 25-hydroxyvitamin D (25(OH)D) and sclerostin levels were measured before and after treatment. Baseline serum 25(OH)D and sclerostin levels were at 5.7±2.4ng/mL and 39.1±14.4pg/mL, respectively. Serum 25(OH)D was significantly increased, to 62.4±18.7ng/mL, following treatment; serum sclerostin was significantly decreased, to 29.3±8.8pg/mL. We conclude that serum sclerostin level is decreased following vitamin D3 treatment in patients with vitamin D deficiency.

Vitamin d status and cardiometabolic risk factors in long-term psychiatric inpatients.

Low vitamin D levels are common in psychiatric patients, but a need for vitamin D supplementation in these individuals remains controversial. Low vitamin D levels are reportedly associated with high prevalence of cardiometabolic risk factors, and both are common in psychiatric patients, but the relationship between diagnosis and severity of illness and cardiometabolic risk status and the effect of vitamin D treatment on them is not known. We studied these relationships and effect of vitamin D(3) treatment on them in 290 long-term psychiatric inpatients. All patients admitted to the hospital during April 2009-March 2010 who agreed to 25-hydroxyvitamin-D testing were included. Serum 25-hydroxyvitamin D level, Brief Psychiatric Rating Scale (BPRS) score, body mass index, blood pressure, and fasting levels of blood glucose, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured at baseline, and changes after vitamin D(3) treatment for up to 12 months were observed. For the purposes of this study, 25-hydroxyvitamin-D levels < 32 ng/mL were considered as "low"; < 20 ng/mL, as "insufficient"; and < 12 ng/mL, as "deficient." A serum 25-hydroxyvitamin-D level < 32 ng/mL was found in 90.0% of patients, and a level <20 ng/mL was found in 48.6% of patients. A BPRS score > 36 was present in 56.0% of patients; obesity, in 75.7%; hypertension, in 44.8%; low HDL-C, in 43.6%; high triglycerides, in 31.2%; high LDL-C, in 17.8%; and increased glucose, in 14.6%. Serum 25-hydroxyvitamin-D levels correlated poorly with BPRS score and the other variables listed above (R, -0.02 to -0.22). After vitamin D(3) treatment, 25-hydroxyvitamin-D level increased to ≥ 20 ng/mL in all patients and ≥ 32 ng/mL in 85% of patients, but despite > 124% increase in mean 25-hydroxyvitamin-D level, mean improvement in other variables was < 12%. Nearly half of our patients had vitamin D levels < 20 ng/mL, putting them at risk for poor bone health and requiring vitamin D supplementation. Cardiometabolic risk factors were also highly prevalent, but correlated poorly with vitamin D levels in their severity. Increasing vitamin D levels to ≥ 32 ng/mL was not associated with improvement in BPRS score or any cardiometabolic risk factor, emphasizing that intensification of therapeutic measures other than vitamin D supplementation is required.

Contribution of GPR30 for 1,25 dihydroxyvitamin D3 protection in EAE

Previous studies have demonstrated that vitamin D3-mediated protection in EAE occurs only in females and is dependent on the presence of diestrus levels of 17β-estradiol (E2). To evaluate the role of estrogen receptors in vitamin D3 treatment of EAE, we compared disease severity, CNS histopathology and immunological responses in vehicle and calcitrol (1,25 dihydroxyvitamin D₃) treated WT C57BL/6 mice vs. GPR30 membrane estrogen receptor (MER) knockout mice with MOG-35-55 peptide-induced EAE. Our results demonstrated that vitamin D₃-mediated prevention of clinical signs, CNS cellular lesions and demyelination observed in WT mice was abrogated in GPR30-KO mice with EAE. Regulatory effects of vitamin D₃ treatment that were MER dependent included increased levels of IL-10 and IL-6 secreted by MOG peptide-reactive splenocytes and increased expression of CCL5, CCR1 & CCR3 in spleen tissue. These results demonstrate for the first time that the MER is a key contributor to the E2-dependent effects of vitamin D₃-mediated protection in EAE.

Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: a pilot study.

Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances, in particular from insulin resistance. Accumulating evidence suggests that vitamin D deficiency may contribute to the development of insulin resistance. Hence, we aimed to examine the effect of vitamin D supplementation on metabolic and endocrine parameters in PCOS women. Fifty-seven PCOS women were included in the study. PCOS women received 20,000 IU cholecalciferol weekly for 24 weeks. Anthropometric measures, oral glucose tolerance test, and blood analyses of endocrine parameters were performed at baseline and after 12 weeks (V2) and 24 weeks (V3). Forty-six PCOS women finished the study. 25-hydroxyvitamin D [25(OH)D] levels significantly increased from 28.0±11.0 ng/ml at baseline to 51.3±17.3 and 52.4±21.5 at V2 and V3, respectively (p<0.001). We observed a significant decrease of fasting and stimulated glucose (V3, p<0.05) and C-peptide levels (V2 and 3, p<0.001) after vitamin D treatment. Moreover, triglyceride and estradiol levels significantly decreased at V3 (p=0.001) and V2 (p=0.022), respectively, whereas total cholesterol (V2, p=0.008) and LDL cholesterol levels (V2, p=0.005; V3, p=0.026) significantly increased after vitamin D treatment. There were no changes in androgens. At V2, 14 out of 46 PCOS women previously affected by menstrual disturbances (30.4%) reported improvement of menstrual frequency; at V3, 23 out of 46 women (50.0%), who were oligo- or amenorrheic at baseline reported improvement. Our results suggest that vitamin D treatment might improve glucose metabolism and menstrual frequency in PCOS women. Further randomized controlled trails are warranted to confirm our findings.

The effect of vitamin D3 on resistance to stress-related infection in an experimental model of turkey osteomyelitis complex

Male turkeys immunosuppressed by injection with dexamethasone (DEX) were given supplemental vitamin D3 in their drinking water in two experiments. In Experiment 1, vitamin D3 was supplemented at a dosage of either 2,064 IU/kg (low level) or 4,128 IU/kg (high level) in drinking water provided ad libitum only from Days 1 through 5 after hatch. In Experiment 2, vitamin D3 was provided at the low dosage for the first 5 d after hatch, followed by treatment with the high dosage for 12 h before and 12 h after each stressful event, which included weekly weighings and two DEX treatments. In both experiments, at 5 wk of age half of the birds were given intramuscular injections of 2 mg/kg DEX on 3 alternating d. In Experiment 1, 100 cfu of Escherichia coli was inoculated into the left thoracic airsac at the time of the third DEX injection. All mortalities were examined, and 10 birds per pen were necropsied 2 wk after treatment and examined for lesions of airsacculitis and turkey osteomyelitis complex (TOC). Four birds per pen were bled before necropsy, and white blood cell total counts, differential white blood cell counts, and clinical chemistry values were determined. In Experiment 2, healthy surviving birds were grown for an additional 5-wk period, after which the DEX-treated birds were given a second series of DEX injections and were bled and necropsied 2 wk later. There were no significant effects of vitamin D3 treatment in combined general linear models analysis of Experiment 1; however, when birds not treated with DEX or E. coli were compared with those treated with both DEX and E. coli, supplementation with the low level of vitamin D3 significantly decreased TOC incidence. There were no significant effects of vitamin D3 treatment in birds treated with DEX at 5 wk of age in Experiment 2. However, when surviving birds were given a second DEX treatment at 12 wk, vitamin D3 treatment resulted in significantly lower incidence of mortality, TOC, green liver, isolation of bacteria from tissues, and lower airsacculitis scores and heterophil-to-lymphocyte ratios than controls. Vitamin D3 also improved BW, relative weights of the liver and heart, and serum levels of glucose and alanine aminotransferase (ALT) of birds receiving two treatments with DEX. The ability of vitamin D3 supplementation to protect turkeys from the immunosuppressive effects of multiple DEX treatments emphasizes the role of vitamin D3 as a prohormone that affects health and disease resistance in turkeys.

Effect of Vitamin D3 Treatment in the Neonatal or Adolescent Age (Hormonal Imprinting) on the Thymic Glucocorticoid Receptor of the Adult Male Rat

Single neonatal treatment with 25 μg vitamin D₃ significantly decreased the thymic glucocorticoid receptor density (B_max) of 6-week-old male rats. In females, a similar treatment did not cause any changes. Single vitamin D₃ treatment (50 μg) during adolescence (i.e. 6-week-old animals) significantly increased the glucocorticoid receptor density in adult (10-week-old) males. No significant changes in receptor affinity (K_d) could be observed. Considering that in earlier experiments similar neonatal treatments influenced bone mineral mass and sexual behavior, the hormonal imprinting effect of vitamin D₃ and its harmful effect on the development of other members of the steroid receptor superfamily, seems to be unquestionable.

Identification of risk factors on secondary hyperparathyroidism undergoing long-term haemodialysis with vitamin D3

In order to evaluate the clinical outcome as well as the effect of vitamin D3 treatment on secondary hyperparathyroidism (SHPT) in the patients undergoing long-term dialysis therapy, we conducted a long-term follow-up survey on the demographic characteristics of 425 patients who were observed for more than 3 years. All patients were treated with daily 1 alpha (OH)D3 treatment after the initiation of dialysis. Among them the percentage of patients needing parathyroidectomy was 4.9%; aggravation of SHPT, 11.8%; an increase of the parathyroid hormone (PTH) level without radiographical abnormalities, 17.4%; stable, 56.2%; and a decrease of the PTH level, 9.7% at the final observation. The average PTH levels increased year by year irrespective of the difference of original renal disease. Gender, age at the start of dialysis, original renal disease, duration of dialysis treatment, the decade of starting dialysis, the degree of phosphate control, and the PTH level at starting dialysis were analysed as potential risk factors for SHPT, and assessed by multivariate analysis. Multivariate analysis revealed that only the terms of duration of dialysis and the PTH level at starting dialysis were the significant risks for developing overt SHPT. Logistic regression analysis revealed that the relative risk was significantly higher in the patients with more than 10 years history of dialysis and in those with the carboxyterminal PTH levels at the start of dialysis being more than 5 ng/ml. These results suggest that the treatment with daily low-dose vitamin D3 administration after dialysis initiation is imperfect; therefore some prophylactic therapy from the predialysis stage is necessary to prevent overt SHPT, which will occur after long-term haemodialysis.

Effect of Vitamin D3 on the in vitro Transport of Calcium by the Chick Intestine

The effect of vitamin D3 treatment of the chick on concentrative transport of calcium by intestinal loops in vitro, on intestinal permeability to calcium in vitro and on calcium efflux from tied-off intestinal loops in situ was determined. Concentrative transport of calcium in vitro could not be demonstrated when chick intestine was incubated in K-H buffer (Na = 145 mM) but was observed when everted intestinal loops were incubated in a low sodium buffer (Na = 26 mM). In this low sodium medium, concentrative transport of calcium was observed only in the ileal segment and was greatly enhanced by vitamin D3 treatment of the chick. Vitamin D3 treatment was also shown to increase the permeability to calcium of the intestinal loop in vitro. In the in vitro preparations calcium was not transferred across the wall of the duodenum. In situ, however, the most rapid efflux of calcium occurred in the duodenal loop and was greatly enhanced by vitamin D treatment.