The effect of vitamin D3 and thyroid hormones on the capillaroscopy-confirmed microangiopathy in pediatric patients with a suspicion of systemic connective tissue disease-a single-center experience with Raynaud phenomenon.

Raynaud phenomenon (RP) may be the first manifestation of a systemic connective tissue disease (SCTD). Early detection of dysfunction of small vessels called microangiopathy is essential for the diagnostic process. The focus of this single-center, retrospective study was to investigate the potential dependencies between microvascular image and laboratory markers measured in children with RP. The study analyzed the nail-fold video-capillaroscopy (NVC) findings and laboratory results of 81 children between the ages 6 and 17 who were referred to pediatric rheumatologist with a suspicion of SCTD. Out of 52 patients presenting with RP at the time of evaluation, abnormalities in capillary microscopic imaging were found in 34. NVC findings were then compared to levels of specific biomarkers in serum. Vitamin D3 serum levels have been significantly decreased in patients with RP (23.4 ng/mL ± 8.76 vs. 30.0 ng/mL ± 12.66, P = 0.0148). There were positive significant correlations between levels of vitamin D3 and acute-phase reactants in serum, such as C-reactive protein (P = 0.0292). Furthermore, free thyroxine levels (fT4) in patients with both RP (P = 0.0126) and micro-angiopathy (P = 0.05496) persisted in the lower range of the normal limit (< 1.0 ng/dL). Regular oral supplementation of vitamin D3 should be always considered in children with RP if deficiency is found. Additionally, low fT4 level (< 1.0 ng/dL) should be considered as an indication to perform NVC in patients suspected of SCTD even when they do not present RP.

Effect of vitamin D3 supplementation during pregnancy on high risk factors - a randomized controlled trial.

OBJECTIVES: Vitamin D plays an important role in the release of the placenta and implantation, and low levels are a risk factor for pre-eclampsia. Studies have also shown that symptomatic treatment of vitamin D3 deficiency can effectively reduce the risk of pre-eclampsia. In this study, vitamin D3 supplementation was performed on the risk of pre-eclampsia to observe its effect. METHODS: From January 2016 to December 2018, 450 women with maternal treatment and delivery in our hospital underwent an open-label randomized study. The pregnant women were divided into low-dose, medium-dose, and high-dose groups. Compare the incidence of pre-eclampsia and the dose effect of vitamin D levels. RESULTS: In the maternal and perinatal periods of the 450 maternal women, the 25[OH] index of the three groups of pregnant women was significantly increased, while the high-dose increase index was more obvious. The relative risk reduction rate was significantly lower. Compared with the low-dose and middle-dose groups, the high-dose group had a significantly lower incidence of pre-eclampsia, while the IUGR index was lower, and other obstetric indicators were comparable. CONCLUSION: Vitamin D supplementation can effectively reduce the incidence of pre-eclampsia, while reducing the IUGR index, which has important value and significance in its clinical application.

Autophagy participates in the protection role of 1,25-dihydroxyvitamin D3 in acute myocardial infarction via PI3K/AKT/mTOR pathway.

Vitamin D deficiency is associated with acute myocardial infarction (AMI); thus we aimed to explore improvement effects of 1,25-dihydroxyvitamin D3 (VD3) on the AMI and its potential mechanism. AMI models were constructed using male C57/BL6J mice and randomly treated with normal saline or VD3, using sham rats as control. Heart functions, myocardial damage, apoptosis, and inflammation were evaluated. Cardiomyocytes isolated from 3-day-old suckling mice were used for in vitro verification. After VD3 treatment, AMI-induced cardiac dysfunction was reversed with better cardiac function parameters. VD3 treatment reduced inflammatory cell infiltration and myocardial infarction area accompanied by the reduction of inflammatory factors and myocardial infarction markers compared with the AMI group. VD3 treatment obviously alleviated AMI-induced myocardial apoptosis, along with Bcl-2 upregulation and downregulation of caspase-3, caspase-9, and Bax. Both in vivo and in vitro experiments revealed that VD3 enhanced the expression of LC3II and Beclin-1 and decreased soluble p62. Furthermore, VD3 enhanced the AMI-caused inhibition of PI3K, p-AKT, and p-mTOR expression, which was conversely reversed by the addition of 3-methyladenine in vitro. The study highlights the improvement effects of VD3 on cardiac functions. We proposed a potential mechanism that VD3 protects against myocardial damage, inflammation, and apoptosis by promoting autophagy through PI3K/AKT/mTOR pathway.

Effect of Short-Term Sunlight Exposure on Blood Pressure and Pulse Rate in Vitamin D3-Insufficient, Prehypertensive Patients: A Pilot Study.

INTRODUCTION: This study was conducted to evaluate the effect of short-term sunlight exposure on blood pressure (BP) and pulse rate (PR) in vitamin D3-insufficient, prehypertensive patients. METHODS: Twenty prehypertensive male participants were prospectively enrolled in this pilot study. BP and PR were measured using 24-hour ambulatory BP monitoring and endocrine biomarkers were assessed. RESULTS: Sunlight exposure decreased 24-hour systolic BP (SBP), diastolic BP (DBP), and PR (SBP: 132.6 mm Hg to 129.3 mm Hg, DBP: 77.6 mm Hg to 75.7 mm Hg, and PR: 76.1 bpm to 71.3 bpm, p values: 0.0011, 0.0012, and <0.0001, respectively). The decrement patterns of SBP, DBP, and PR during nighttime (SBP: 123.5 mm Hg to 117.9 mm Hg, DBP: 72.2 mm Hg to 68.0 mm Hg, and PR: 68.2 bpm to 59.1 bpm, p values: 0.0015, 0.0003, and <0.0001, respectively) were more profound compared between daytime and nighttime. Blood levels of 25-hydroxyvitamin D3 were significantly increased (p = 0.0001) but aldosterone levels were significantly decreased (p = 0.0014) after sunlight exposure. In addition, an inverse relationship between 25-hydroxyvitamin D3 and aldosterone levels was observed (R = -0.4709, p = 0.0419). DISCUSSION/CONCLUSION: The pilot study gives promising results that it is worthwhile to evaluate short-term sunlight exposure as a potentially effective approach in decreasing BP and PR in 25-hydroxyvitamin D3-insufficient prehypertensive patients in a larger trial with a control group.

The role of cholecalciferol deficiency in the pathogenesis of polycystic ovary syndrome.

OBJECTIVES: to evaluate and compare clinical presentations, medical history, and laboratory data of patients with polycystic ovary syndrome, including vitamin 25(OH)D3 level. METHODS: In total, 81 patients were examined. The patient group included 51 patients with signs of polycystic ovary syndrome. The control group included 30 healthy women without signs of polycystic ovary syndrome, comparable according to gender and age to the patient group. Polycystic ovary syndrome was verified based on the diagnostic Rotterdam and international polycystic ovary syndrome guidelines' criteria. The levels of cholecalciferol were determined by mass spectrometry (ng/mL). At the second stage of the study, the patient group with polycystic ovary syndrome was divided into two subgroups depending on the waist circumference and compared with each other by the level of insulin, low-density lipoproteins, triglycerides, anti-Mullerian hormone, follicle-stimulating hormone, and luteinizing hormone. Statistical analysis was carried out using the parametric t-test for two-independent samples with equal or different variance. For nominal data-Pearson's chi-test, when the means are not calculated and a test is carried out for the presence of a relationship between the nominal variables. RESULTS: Patients with polycystic ovary syndrome and without polycystic ovary syndrome did not have a statistically significant difference in 25(OH)D3 level. Statistically significant differences in the level of 25(OH)D3 were found in women with polycystic ovary syndrome with the waist circumference ⩾80 cm. In these subgroups, differences in insulin, low-density lipoprotein, and triglycerides levels were also revealed. CONCLUSION: The correlation of the 25(OH)D3 level does not differ in the groups of patients with polycystic ovary syndrome and without polycystic ovary syndrome, but significantly correlates with the metabolic profile of patients.

El efecto de la vitamina D3 y su relación. con el nivel de glóbulos blancos en las mujeres con aborto espontáneo, inyección intracitoplasmática de espermatozoides (ICSI) técnicao / The effect of vitamin D3 and its relationship with the level of white blood cells in women spontaneous miscarriage undergoing intracytoplasmic sperm injection (ICSI) technique

Women were studied undergoing ICSI for 84 who suffer non-pregnancy at the Fertility Center, Al-Sadr Medical Hospital in Najaf Governorate, Period between January 2019 and March 2020. WBC, Vitamin D3 and ß-hCG were measured, The pregnant women was divided into (Pregnancy Group, and spontaneous miscarriage) and then demonstrate the immunological effect on pregnancy of women after ICSI technique. Current resultsstudy showed a significant increase (p<0.05) in hormone level ß-hCG is evidence of the presence of high success rates for pregnancy in women who performed operations IVF, where the success rate at the beginning of the matter reached 61.9%, after which it decreased to 33.3% after the first three months due to the occurrence of spontaneous miscarriage of pregnant women due to various immunological and physiological reasons, a positive correlation between the level of ß-hCG and other parameters in the study (Vitamin D3 -WBC).Also The current resultsshowed a significant decrease in a groups (pregnancy failure) and the group (spontaneous miscarriage) compared with the control group (continued pregnancy) in relation to the level of vitamin D3 Also, The current results showed a significant increasein (pregnancy failure) and (spontaneous miscarriage) compared with control groups (continuation of pregnancy) in relation WBC numbers, and the present study founds a negative relationship between the level of vitamin D3 and WBC.

Is cholecalciferol a potential disease-modifying anti-rheumatic drug for the management of rheumatoid arthritis?

Vitamin D is a pleiotropic molecule with a well-characterised immunomodulatory activity in vitro; however, its potential clinical application in autoimmune conditions has yet to be clarified. Several authors have investigated the use of vitamin D as a disease-modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA), obtaining divergent conclusions. This systematic review summarises and critically analyses the findings of papers assessing the impact of vitamin D supplementation on pain relief, disease activity, functional status and flare rate. We conclude that the correction of hypovitaminosis D may have a beneficial effect on pain perception; moreover, the achievement of an adequate plasma vitamin D concentration obtained with high-dose regimens might evoke immunomodulatory activities of vitamin D and favourably impact on disease control. Nevertheless, the current evidence is still not strong enough to support the use of cholecalciferol as a DMARD in RA, and further studies are required to clarify this issue.

An epidemiology survey of vitamin D deficiency and its influencing factors.

BACKGROUND: There is growing evidence that vitamin D is related to the development of a variety of diseases. The current study was performed to investigate the status of serum vitamin D distribution among adult Chinese people and reveal the influence of gender, age, seasonality and residential regions on serum vitamin D levels. METHOD: This cross-sectional study included 14,302 participants aged from 18 years old to 65 years old from six major cities in China. The basic demographic information and the levels of serum vitamin D (25(OH)D) and vitamin D3 (25(OH)D3) were collected from Jan 2, 2014 to Dec 25, 2017. RESULT: The prevalence of 25(OH)D3 concentration <30ng/mL reached up to 83%, in which the rate of vitamin D insufficiency (20-29ng/mL) was 32.7%, and vitamin D deficiency (10-19ng/mL) accounted for 41.9%, and vitamin D severe shortage (<10ng/mL) accounted for 8.4%. Women were more likely to have vitamin D3 deficiency and lower serum vitamin D3 concentration than men (both p<0.001). The mean concentration of serum 25(OH)D and 25(OH)D3 in summer and autumn were higher than that in spring and winter (p<0.001), and the mean concentration of serum 25(OH)D in people from Southern China was higher than that in people from other regions (p<0.001). Although the mean concentrations of serum 25(OH)D and 25(OH)D3 were both increased by age, the percentage of patients with serum 25(OH)D3 insufficiency was also increased. CONCLUSION: Serum vitamin D deficiency is very common in adults in China. The level of serum vitamin D may be associated with age, sex, seasonality and residential regions.

Vitamin D deficiency induces the excitation/inhibition brain imbalance and the proinflammatory shift.

Vitamin D3 is among the major neurosteroids whose role in developing and adult brain is intensively studied now. Its active form 1,25(OH)2D3 regulates the expression and functioning of a range of brain-specific proteins, which orchestrate the neurotransmitter turnover, neurogenesis and neuroplasticity. Despite numerous studies of the vitamin D role in normal and pathological brain function, there is little evidence on the mechanisms of alterations in excitatory and inhibitory neurotransmission under vitamin D deficiency (VDD). Using the animal model we characterized the dysfunction of excitatory and inhibitory neurotransmission under alimentary VDD. The shift between unstimulated and evoked GABA release under VDD was largely reversed after treatment of VDD, whereas the impairments in glutamatergic system were only partially recovered after 1-month vitamin D3 supplementation. The increase of the external glutamate level and unstimulated GABA release in brain nerve terminals was associated with intensified ROS production and higher [Ca2+]i in presynapse. The negative allosteric modulation of presynaptic mGlu7 receptors significantly enhanced exocytotic GABA release, which was decreased under VDD, thereby suggesting the neuroprotective effect of such modulation of inhibitory neurotransmission. Synaptic plasma membranes and cytosolic proteins contribute to the decreased stimulated release of neurotransmitter, by being the crucial components, whose functional state is impaired under VDD. The critical changes with synaptic vesicles occurred at the docking step of the process, whereas malfunctioning of synaptic cytosolic proteins impacted the fusion event foremost. The decreased amplitude of exocytosis was inherent for non-excitable cells as well, as evidenced by lower platelet degranulation. Our data suggest the presynaptic dysfunction and proinflammatory shift as the early events in the pathogenesis of VDD-associated disorders and provide evidences for the neuroprotective role of vitamin D3.

Free vitamin D levels in steroid-sensitive nephrotic syndrome and healthy controls.

INTRODUCTION: Body stores of vitamin D are measured as "total" serum 25-hydroxy vitamin D (25(OH)D). Its largest component is protein bound and lost in urine in nephrotic syndrome (NS). Our study investigates whether "free" 25(OH)D levels are a better guide to bone health and need for vitamin D supplementation in patients with steroid-sensitive NS (SSNS). METHODS: A cross-sectional study was performed in children with SSNS and healthy controls. Blood was tested for albumin, creatinine, calcium, phosphate, ALP, total and free (by direct ELISA) 25(OH)D, iPTH, and urine for protein-creatinine ratio. RESULTS: Seventy-nine NS patients (48 in relapse, 31 in remission) and 60 healthy controls were included. The levels of total 25(OH)D were significantly different (lowest in NS relapse and highest in controls) (p < 0.001). Corrected calcium and phosphate levels were normal, and there were no differences in free 25(OH)D, ALP, or iPTH levels between groups. Only total and not free 25(OH)D correlated significantly and negatively with urinary protein creatinine ratios (rs = - 0.42 vs. 0.04). Free 25(OH)D values of 3.75 and 2.85 pg/ml corresponded to total 25(OH)D levels of 20 and 12 ng/ml, respectively, in healthy controls. CONCLUSION: These results confirm that total 25(OH)D levels are low in NS and related to degree of proteinuria. However levels of free 25(OH)D, ALP, and iPTH did not change in relapse or remission in comparison with healthy controls. Our results suggest that in proteinuric renal diseases, free 25(OH)D rather than total 25(OH)D levels should be used to diagnose vitamin D deficiency and guide therapy.

Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE).

OBJECTIVE: To evaluate the safety and efficacy of cholecalciferol in patients with relapsing-remitting MS (RRMS). METHODS: In this double-blind, placebo-controlled parallel-group, 2-year study, 181 patients with RRMS were randomized 1:1. Key inclusion criteria were a low serum 25-hydroxy vitamin D (25OHD) concentration (<75 nmol/L), a treatment with interferon beta-1a 44 µg (SC 3 times per week) 4 months ± 2 months before randomization, and at least one documented relapse during the previous 2 years. Patients received high-dose oral cholecalciferol 100,000 IU or placebo every other week for 96 weeks. Primary outcome measure was the change in the annualized relapse rate (ARR) at 96 weeks. Secondary objectives included safety and tolerability of cholecalciferol and efficacy assessments (ARR, MRI parameters, and Expanded Disability Status Scale [EDSS]). RESULTS: The primary end point was not met. In patients who completed the 2-year follow-up (45 with cholecalciferol and 45 with placebo), all efficacy parameters favored cholecalciferol with an ARR reduction (p = 0.012), less new hypointense T1-weighted lesions (p = 0.025), a lower volume of hypointense T1-weighted lesions (p = 0.031), and a lower progression of EDSS (p = 0.026). The overall rate of adverse events was well balanced between groups. CONCLUSIONS: Although the primary end point was not met, these data suggest a potential treatment effect of cholecalciferol in patients with RRMS already treated with interferon beta-1a and low serum 25OHD concentration. Together with the good safety profile, these data support the exploration of cholecalciferol treatment in such patients with RRMS. CLINICALTRIALSGOV IDENTIFIER: NCT01198132. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS and low serum 25OHD, cholecalciferol did not significantly affect ARRs.

[Analysis of the relationship between vitamin D3 level and disease severity in hereditary angioedema]. / A D3-vitamin-szint és a betegség súlyossága közötti kapcsolat vizsgálata herediter angioödémában.

Introduction: In recent years, many papers analyzed the relationship between serum vitamin D3 level and the frequency and activity of various diseases at least partially attributed to immune mechanisms. Aim: We looked for correlations among the number and location of edematous episodes occurring in patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) and the quantity of the C1-inhibitor used for supplementation as well as the vitamin D3 levels of patients. Method: We measured vitamin D3 levels in 118 of the 175 C1-INH-HAE patients of the National Angioedema Reference Center during the winter-spring (n = 111) and the summer-autumn periods (n = 105) in 2013-2014. Complement levels and clinical data were extracted from the National Angioedema Registry and from patient diaries. Results: The proportion of vitamin D3 deficient patients (serum level <20 ng/ml) was approximately 59.5% during winter-spring, 27.6% in summer-autumn, and 23.5% during both periods. There was a significant difference between vitamin D3 serum levels measured in the winter-spring or in the summer-autumn months (p<0.0001). The same applies to the number of the vials of C1-inhibitor concentrate administered as acute treatment for angioedema attacks (p = 0.01). In any season, vitamin D3 level did not correlate with the number of attacks experienced by the patients during the given period or of the vials of C1-inhibitor concentrate administered. Conclusions: We could not demonstrate a relationship between vitamin D3 level and the frequency or location of edematous episodes in HAE patients. The need for treatment (as reflected by the number of the vials administered) was higher in the winter-spring period. As vitamin D3 deficiency was more severe than expected in our patients, supplementation is clearly necessary. Orv Hetil. 2019; 160(25): 987-993.

Radiographic alveolar bone level and levels of serum 25-OH-Vitamin D3 in ethnic Norwegian and Tamil periodontitis patients and their periodontally healthy controls.

BACKGROUND: Studies suggest association between low serum 25-OH-Vitamin D3 (VitD) and chronic destructive periodontal diseases. The main sources of VitD is sun exposure and fat fish. Subjects with dark skin will therefore generate less VitD as response to sun exposure. The aim of the study was to assess the radiographic bone level and levels of serum VitD in ethnic Norwegian and Tamil periodontitis patients and their respective healthy controls. METHODS: Twenty-seven Tamil periodontitis patients living in Norway were compared to 21 Tamil controls as well as to 21 Norwegian periodontitis patients and 23 Norwegian controls. Marginal bone level was diagnosed on radiographs. VitD levels were diagnosed in blood samples by high-performance liquid chromatography-mass spectrometry. RESULTS: VitD levels were lower in Norwegian periodontitis patients than in controls, while no significant differences were observed between Tamil periodontitis patients and controls despite the significant difference between RBL between the periodontitis patients and controls in both groups. When calculating the odds ratio for having periodontal disease in both populations together, it appeared that one unit increased serum VitD (i.e. 1 nmol/L) decreased the odds of having radiographic bone loss by 4%. CONCLUSION: According to logistic regression, and after correcting for confounding factors, VitD levels showed significant association with the presence of periodontitis, as expressed by radiographic bone loss, in all patients combined.

Dietary Vitamin D3 Deficiency Increases Resistance to Leishmania (Leishmania) amazonensis Infection in Mice.

The leishmaniases are a group of diseases caused by Leishmania parasites, which have different clinical manifestations. Leishmania (Leishmania) amazonensis is endemic in South America and causes cutaneous leishmaniasis (CL), which can evolve into a diffuse form, characterized by an anergic immune response. Since the leishmaniases mainly affect poor populations, it is important to understand the involvement of immunonutrition, how the immune system is modulated by dietary nutrients and the effect this has on Leishmania infection. Vitamin D3 (VitD) is an immunonutrient obtained from diet or endogenously synthesized, which suppresses Th1 and Th17 responses by favoring T helper (Th) 2 and regulatory T cell (Treg) generation. Based on these findings, this study aims to evaluate dietary VitD influence on L. (L.) amazonensis experimental infection in C57BL/6 and BALB/c mice. Thus, C57BL/6 and BALB/c VitD deficient (VDD) mice were generated through dietary VitD restriction 45 days prior to infection. Both strains of VDD mice showed a more controlled lesion development compared to mice on a regular diet (Ctrl). There were no differences in serum levels of anti-Leishmania IgG1 and IgG2a, but there was a decrease in IgE levels in BALB/c VDD mice. Although CD4+ T cell number was not changed, the CD4+ IFN-y+ T cell population was increased in both absolute number and percentage in C57BL/6 and BALB/c VDD mice compared to Ctrl mice. There was also no difference in IL-4 and IL-17 production, however, there was reduction of IL-10 production in VDD mice. Together, our data indicate that VitD contributes to murine cutaneous leishmaniasis susceptibility and that the Th1 cell population may be related to the resistance of VDD mice to L. (L.) amazonensis infection.

Effect of Vitamin D on Cognitive Functions in Older Adults: 24-Week Follow-Up Study.

The purpose of this study is to assess the effect of vitamin D replacement on cognitive function in older adults. A total of 560 patients who underwent comprehensive geriatric assessment including Global cognitive assessment, Basic Activities of Daily Living (BADL), and Instrumental Activities of Daily Living (IADL) twice in 6-month period were retrospectively reviewed. Oral cholecalciferol was replaced to patients with vitamin D deficiency routinely. In baseline cognitive scores, BADL-IADL scores were lower in the severe deficiency group than in the deficiency and adequate groups (P < .05). With regard to the relation between changes in cognitive functions, BADL-IADL scores on the 6-month versus baseline, no difference was determined in patients with and without dementia (P > .05). Vitamin D replacement may not improve cognitive performance in older adults, even if vitamin D is raised to adequate level, suggesting that longer term replacement therapy may be needed to improve cognitive function.

Hypovitaminosis D exacerbates the DNA damage load in human uterine fibroids, which is ameliorated by vitamin D3 treatment.

Uterine fibroids (UFs) are the most common benign neoplastic threat to women's health and associated with DNA damage and genomic instability. Hypovitaminosis D is a known risk factor for UFs, especially among African Americans. Vitamin D3 has been shown to effectively inhibit UF phenotype, but its mechanisms remain unclear. We hypothesize that Vitamin D3 ameliorates UFs by recovering the damaged DNA repair system, thus inhibits tumor progression. We compared the DNA damage status and Vitamin D receptor (VDR) expression between normal myometrial and UF primary cells. Unrepaired DNA double-strand breaks (DSBs) accumulated but VDR expression decreased in UFs. The RNA and protein levels of key DNA repair members belonging to DNA DSB sensors (MRE11, NBS1, RAD50), mediators and effectors (CHECK2, BRCA1, RAD51) were downregulated in UFs compared with myometrial cells. VDR KD induced DSB accumulation and DNA damage response (DDR) defects in myometrial cells. Using the DNA damage PCR array, the expression of many additional DNA repair genes was downregulated in VDR KD cells. Treatment of UF cells with Vitamin D3 (100 nM) significantly decreased DNA damage and restored DDR concomitant with VDR induction. Notably, the PCR array demonstrated that among 75 downregulated genes after VDR KD, 67 (89.3%) were upregulated after vitamin D3 treatment. These studies demonstrate a novel link between DNA damage and the vitamin D3/VDR axis in UFs. Vitamin D3 suppresses the UF phenotype through orchestrated targeting at multiple molecules in DNA repair pathways, thus offering novel mechanistic insights into the clinical effectiveness of vitamin D3 on UFs.

Vitamin D3 deficiency in puberty rats causes presynaptic malfunctioning through alterations in exocytotic release and uptake of glutamate/GABA and expression of EAAC-1/GAT-3 transporters.

Recent experimental and epidemiologic investigations have revealed that the central nervous system is a target for vitamin D3 action and also linked vitamin D3 deficiency to Alzheimer's and Parkinson's disease, autism and dementia. Abnormal homeostasis of glutamate and GABA and signaling disbalance are implicated in the pathogenesis of major neurological diseases. Here, key transport characteristics of glutamate and GABA were analysed in presynaptic nerve terminals (synaptosomes) isolated from the cortex of vitamin D3 deficient (VDD) rats. Puberty rats were kept at the VDD diet up to adulthood. VDD caused: (i) a decrease in the initial rates of L-[14C]glutamate and [3H]GABA uptake by plasma membrane transporters of nerve terminals; (ii) a decrease in exocytotic release of L-[14C]glutamate and [3H]GABA; (iii) changes in expression of glutamate (EAAC-1) and GABA (GAT-3) transporters. Whereas, the synaptosomal ambient levels and Ca2+-independent transporter-mediated release of L-[14C]glutamate and [3H]GABA were not significantly altered in VDD. Vitamin D3 is a potent neurosteroid and its nutritional deficiency can provoke development of neurological consequences changing glutamate/GABA transporter expressions and excitation/inhibition balance. Also, changes in glutamate transport can underlie lower resistance to hypoxia/ischemia, larger infarct volumes and worsened outcomes in ischemic stroke patients with VDD.

Evaluation of vitamin D3 deficiency: A population-based study in northeastern Iran.

BACKGROUND AND AIM: In recent years, vitamin D deficiency has become a major worldwide problem that can exert harmful effects. The aim of the present study was to evaluate the sex- and age-related prevalence of vitamin D deficiency in people from Mashhad, northeastern Iran. METHODS: In this cross-sectional study conducted over a period of 1 year (2015-2016), 7504 subjects who referred to Mashhad medical centers were randomly enrolled in the study. The study population was divided into four groups based on sex and age, as following: group 1, 6 to 18 years; group 2, 19 to 35 years; group 3, 36 to 50 years; and group 4, 51 to 65 years. Since vitamin D levels <10, 10 to 20, and 20 to 30 ng/mL are considered as severe, moderate, and mild deficiency, respectively, we used these criteria for categorizing our population. RESULTS: Of the total population in our study, 65.26% (4902; 57.81% of men and 72.07% of women) showed some degree of vitamin D deficiency. In addition, we found that vitamin D deficiency was common in all age groups (6-18, 19-35, 36-50, and 51-65 years), and more common in women (58.5%, 80.12%, 63.83%, and 88.44%, respectively) than men (41.66%, 59.86%, 44.97%, and 84.75%, respectively). CONCLUSION: Vitamin D deficiency is a major health problem in all age groups and is more common in women. This information would help to provide a progressive prevention program to maintain health and manage some of the vitamin-related disorders and diseases that especially affect women.

Vitamin D deficiency and its health effects.

Vitamin D3 cholecalciferol is produced from its cholesterol precursors in the skin under the influence of ultraviolet calc. Its subsequent hydroxylation in the liver and kidneys leads to the formation of its most active metabolite calcitriol, which plays one of the key roles in the management of calcium phosphate metabolism. However, it also has the ability to regulate the function of a number of cells and tissues that express the vitamin D receptor. The most widespread method to evaluate the status of vitamin D in the body is to measure serum levels of its meta-bolite 25 hydroxyvitamin D - 25 (OH) D. Optimal values range between 75-125 nmoll / l. Its deficit is widespread in the human population worldwide and has a significant impact on the prevalence of metabolic bone diseases. Its deficiency may support the dysfunction of many other body systems. Ensuring optimal levels of vitamin D in the popula-tion is a challenge not only for health care and especially for government administration.

Modulation of neurosecretion and approaches for its multistep analysis.

BACKGROUND: Neurosecretion is the multistep process occurring in separate spatial and temporal cellular boundaries which complicates its comprehensive analysis. Most of the research are focused on one distinct stage of synaptic vesicle recycling. Here, we describe approaches for complex analysis of synaptic vesicle (SV) endocytosis and separate steps of exocytosis at the level of presynaptic bouton and highly purified SVs. METHODS: Proposed fluorescence-based strategies and analysis of neurotransmitter transport provided the advantages in studies of exocytosis steps. We evaluated SV docking/tethering, their Ca2+-dependent fusion and release of neurotransmitters gamma-aminobutyric acid (GABA) and glutamate in two animal models. RESULTS: Approaches enabled us to study: 1) endocytosis/Ca2+-dependent release of fluorescent carbon nanodots (CNDs) during stimulation of nerve terminals; 2) the action of levetiracetam, modulator of SV glycoprotein SV2, on fusion competence of SVs and stimulated release of GABA and glutamate; 3) impairments of several steps of neurosecretion under vitamin D3 deficiency. CONCLUSIONS: Our algorithm enabled us to verify the method validity for multidimensional analysis of SV turnover. By increasing SV docking and the size of readily releasable pool (RRP), levetiracetam is able to selectively enhance the stimulated GABA secretion in hippocampal neurons. Findings suggest that SV2 regulates RRP through impact on the number of docked/primed SVs. GENERAL SIGNIFICANCE: Methodology can be widely applied to study the stimulated neurosecretion in presynapse, regulation of SV docking, their Ca2+-dependent fusion with target membranes, quantitative analysis of expression of neuron-specific proteins, as well as for testing the efficiency of pre-selected designed neuroactive substances.