Vit D3 Research Articles

SAT224 Nonsurgical Hypoparathyroidism: 40 Years After Diagnosis

Abstract Disclosure: L.I. Kaplan: None. A. Yuen: None. P.D. Greenberg: None. Background: The majority of cases of hypoparathyroidism occur after neck surgery. The most common nonsurgical cause is autoimmune, either in isolation or part of Autoimmune Polyglandular Syndrome Type 1. Hypomagnesemia is a functional cause. Hypoparathyroidism can occur as part of genetic syndromes that include congenital anomalies, short stature and developmental delay. Non-syndromic genetic etiologies including Autosomal Dominant Hypocalcemia type 1 (ADH1), a gain of function mutation in the calcium sensing receptor (CaSR) that can present in infancy, childhood or adulthood with hypocalcemia (50% symptomatic), hypercalcuria (10%) and basal ganglia calcification (35%). For ADH1, targeted therapies are being developed. Clinical Case: A 90-year-old male was diagnosed with hypoparathyroidism at age 50 when he presented with hand cramping and was found to have hypocalcemia with low PTH. He was started on calcitriol and calcium supplementation. Many years later he started following at our endocrine clinic. Past medical history includes prostate cancer treated with radiation and androgen deprivation therapy, HTN, and pre-diabetes. He has no history of neck surgery, other endocrinopathies, candidiasis, vitiligo or congenital anomalies. He has no family history of hypocalcemia and has two children without calcium abnormalities. His DEXA shows stable +T scores in LS spine and bilateral hips. He has not had brain imaging. Nephrocalcinosis was not reported on renal ultrasound. More than 10 years ago, he presented with severe hypercalcemia, acute renal failure (Ca 13.5 mg/dl, Cr 6.0mg/dl, Phos 5.5mg/dl) and ureteral stones after taking over the counter calcium supplements in excess. He underwent stone removal with return to baseline renal function. Subsequently, he underwent knee replacement surgeries and required IV calcium until he was able to swallow pills. Since this time, he has been managed on calcitriol, calcium carbonate, vitamin D3, and chlorthalidone with close follow up for adjustment of regimen to target Ca 8.0-8.5 mg/dl. He has not had a recurrence of severe hypercalcemia, hyperphosphatemia or nephrolithiasis. He feels well and lives at home with his wife. Lab values over the past 10 years are as follows: Ca 8.1-10.6 mg/dl (8.5-10.5), Alb 4.0-4.6 g/dl (3.5-5.4), Phos 4.3-5.5 mg/dl (2.8-4.5), Mg 1.7-1.9 mg/dl (1.3-2.1), K 3.7-4.4 mEq/L (3.6-5.2), Cr 1.0-1.5 mg/dl (0.5-1.3), PTH 0.00-1.4 pg/ml (10-55), 25 OH Vit D 18-58 ng/ml (32-100), 1,25 OH Vit D3 25.5-37.2 pg/ml (19.9-79.3), 24hr Urine Ca 162- 384 mg/24 hrs (50-400). Clinical lessons: Chronic hypoparathyroidism can be well managed with close follow up and frequent lab monitoring. This patient should be referred for genetic testing, particularly to look for ADH1 mutation in the CaSR gene as targeted treatments are being developed. His children should be tested for any mutations found in him. Presentation: Saturday, June 17, 2023

Evaluation of serum anti-Müllerian hormone concentrations following treatment with vitamin D in Holstein Friesian heifers.

Anti-Müllerian hormone (AMH) levels in the blood of dairy cattle are associated with the count of antral follicles (AFC), ovarian function. Numerous studies, particularly in human medicine, have shown that vitamin D3 (Vit D3) has a positive effect on AMH levels. To our knowledge, the effects of Vit D3 on serum AMH levels in heifers have not been investigated. The goal of the current study was to evaluate the concentrations of serum AMH in dairy heifers following Vit D3 treatment. The study included 20 healthy non-pregnant Holstein Friesian heifers. These animals came to estrus at least once. All heifers received a single intramuscular dosage of 5 million IU Vit D3 (Cholecalciferol). Blood samples were collected from the coccygeal veins of all animals before and after Vit D3 injection (days 7, 14, and 28) for the measurement of AMH and 25(OH)D concentrations. In our analysis, we observed that after exogenous Vit D3 administration, circular 25(OH)D increased constantly (up to day 28 after Vit D3 injection) in all animals. On day 28, AMH concentrations saw a 10% increase in comparison with those measured the day before the Vit D3 injection. However, a comparison of AMH concentrations measured across days did not reveal statistically significant differences between Day 0, 7, 14, and 28 levels (p = .10). Furthermore, no statistical correlation was observed between the pairs (age-AMH) and (weight-AMH). Considering all times, no correlation was found between 25(OH)D and blood AMH levels. These findings demonstrated that exogenous Vit D3 did not affect serum AMH in Holstein Friesian heifers.

Vitamin (D) levels in children of families with a case of rheumatic fever or rheumatic heart disease

Background The most prevalent acquired heart illnesses in children are rheumatic fever (RF) and rheumatic heart disease (RHD). Differential regulation of innate immune cell subsets by vitamin D has been shown to effect cell maturation, metabolism, antigen presentation as well as cytokine and chemokine response and production. Aim The aim of this work was to evaluate vitamin D levels in children with acute RF and its relation to serum immunoglobulin levels. Patients and methods This cross-sectional study was conducted at Tanta University Hospital, Pediatric cardiology unit, outpatient clinic, and clinical pathology unit in two groups: group 1 which included 49 children who were subdivided into: group 1a: which included 10 RF or RHD patients and group 1b: included 39 children (brothers or sisters of rheumatic patients). Group 2 (control group): included 40 apparently healthy children of matched age and sex. All patients were subjected to full history taking, echocardiographic examination and laboratory investigations (Vitamin D3, erythrocyte sedimentation rate, antistreptolysin O titre, C-reactive protein (CRP), Calcium (Ca), phosphorus, immunoglobulins G (IgG), complement 3 (C3), and complement 4 (C4). Results There is a statistically significant decrease Ca, C4, and vit D3 levels in patient group compared with the control group. Vitamin D level was positively correlated with C4 levels. There is no statistically significant change was recorded regarding Ph, immunoglobulins G, or C3. Conclusion Children with RHD and children in families with RF or RHD are risky for vitamin D deficiency.

Vitamin D3 supplementation improves spatial memory, muscle function, pain score, and modulates different functional physiological biomarkers in vitamin D3 deficiency diet (VDD)-induced rats model

BackgroundVitamin D Deficiency is recognized as a pandemic, which is associated with high mortality. An inadequate level of vitamin D is associated with autoimmune diseases, hypertension, and cancer. The study was aimed to assess the pharmacological effects of chronic vitamin D3 supplementation on the manipulation diet regiment of deprived cholecalciferol (vitamin D3 deficient diet, VDD) rats.MethodsMemory performance (Y-maze task), muscular function (muscle grip strength), and pain score (pressure application measurement meter) were measured. Functional biomarkers were measured using ELISA method in different matrix viz. in serum (parathyroid hormone; PTH, calcitonin, thyroxine, and C-reactive protein; CRP, 25-OH Vit D3), and in CSF (klotho and β-endorphin). 25-OH Vit D3 was also estimated in liver and kidney homogenate using ELISA. Vitamin D receptor (VDR) was measured spectrophotometrically in liver and adipose tissue.ResultsVDD-induced rats showed a decrease in number of entries and time spent in the novel arm and spontaneous alternations in the Y-maze task. Significant improvements of neuromuscular function and pain score after addition of vitamin D3. In comparison to the VDD group, VDR expression (liver) and active metabolites of vitamin D3 (25-OH vit.D3) in serum were significantly higher by 48.23% and 280%, respectively. The PTH and CRP levels were significantly reduced by 32.5% and 35.27%, respectively, whereas calcitonin was increased by 36.67% compared with the VDD group. Klotho and β-endorphin expressions in cerebrospinal fluid were significantly elevated by 19.67% and 133.59%, respectively, compared to VDD group.ConclusionsOverall, the results indicate that supplementation of cholecalciferol significantly improved spatial memory impairment, VDR expression, and may provide an opportunity to manage vitamin D deficiencies.

A comparative absorption study of sucrosomial® orodispersible vitamin D3 supplementation vs. a reference chewable tablet and soft gel capsule vitamin D3 in improving circulatory 25(OH)D levels in healthy adults with vitamin D deficiency-Results from a prospective randomized clinical trial.

Vitamin D (Vit D) deficiency (VDD), associated with diverse health conditions, is commonly treated with Vit D3 supplements. However, the gastrointestinal (GI) absorption of Vit D3 in different formulations has not been well studied. We aimed to compare the absorption of an innovative phospholipids-sucrester matrix biodelivery vehicle-based (sucrosomial®) orodispersible Vit D3 preparation against a reference chewable tablet and soft gel capsule (SGC) Vit D3 formulations in Vit D-deficient healthy adults. In study 1, 25 subjects were randomized to receive a weekly single dose of 200,000 IU of sucrosomial® Vit D3 (n = 12) or chewable tablet Vit D3 (n = 13) for 3 weeks. In study 2, 20 subjects were randomized to receive a single dose of 200,000 IU every other week of sucrosomial® Vit D3 (n = 10) or SGC Vit D3 (n = 10) for 6 weeks. Circulatory 25-hydroxyvitamin D3 [25(OH)D] levels were reassessed after 2, 3, and 6 weeks in study 1 and after 4 and 6 weeks in study 2. In study 1, after 2 weeks, circulatory 25(OH)D levels increased significantly in both Vit D3 treatment groups (p < 0.0001) but improved markedly in the sucrosomial® Vit D3 group, with no further considerable change after 3 and 6 weeks in both groups. Overall, at all three follow-ups, sucrosomial® Vit D3 treatment achieved significantly higher and sustained 25(OH)D levels (p < 0.001). In study 2, after 4 weeks, both Vit D3 treatment groups showed significant improvement in circulatory 25(OH)D levels (p < 0.0001) but substantially higher in the sucrosomial® group with statistically significant differences between the two treatment groups (p = 0.02). At the 6-week follow-up, only subjects in the sucrosomial® Vit D3 group showed a further increase in circulatory 25(OH)D levels (p = 0.049), but no further significant changes in the levels of the SGC Vit D3 group (p = 0.062), showing a statistically significant difference between the two treatment groups (p = 0.002). The Vit D3 treatment was well tolerated by all participants, and no treatment-emergent effects or serious adverse events were reported. Our results suggest that the sucrosomial® Vit D3 preparation absorbs efficiently in the GI system, achieving adequately higher and sustained circulatory Vit D levels in VDD, and thus can effectively contribute to the body protection against VDD-associated health conditions. clinicaltrials.gov, identifier: NCT05706259.

Supplements and Their Role in Reducing Chronic Kidney Disease Progression

Conservative treatment of chronic kidney disease, apart from simply treating symptoms and associated complications, consists in slowing chronic kidney disease progression, in order to improve patient and family quality of life, to postpone the need for renal replacement therapy and to reduce the treatment costs. Slowing chronic kidney disease progression involves therapeutic strategies, aiming to avoid/treat malnutrition and inflammation, correct anemia, treat mineral bone disorders of CKD and correct vitamin, mineral and microelement’s deficit. This review aims to shed light to the rationale behind these strategies through evidence from clinical studies and the recent guideline recommendations for use of ketoanalogues, essential aminoacids, calcium, Vit D3, iron, Vit B12, folates and unsaturated fatty acid supplements.

EFFECT OF CHOLECALCIFEROL SUPPLEMENTATION ON HEPATIC STEATOSIS AND GLUCOSE IN OBESE ANIMALS

Our proposal in this study is that with vitamin D supplementation in obese animals, there willbe reductions in hepatic steatosis and control of blood glucose levels. Male wistar rats wereused (CEUA nº 5866200720). After 21 days of age, they were acclimatized until they were 30days old, from this date on, the obesity induction protocol was initiated, by means of thecafeteria diet. The animals were divided into 2 groups: rats fed a normal diet [control group(CTL n= 24)] another with a hypercaloric diet [obesity induction group (WD n=24)]. After 90days old, they were subdivided into two other groups: CTL-VD (n=12) and WD-VD (n=12)animals in which, were supplemented with vitamin D3 (5.600UI/week, 90 to 130 days old, bygavage). At 131 days old, WD rats exhibited a significantly higher adiposity index than CTLand WD-VD rats. The WD-VD rats had a significantly lower adiposity index than WD rats.The hepatic steatosis was confirmed by biochemical measurements of the total liver lipidcontent increased in WD rats 5% of the liver weight. Vit D3 supplementation decreased BWgain, and reduction of the total lipid total liver in WD-VD rats. The glycemic curve wasperformed and the WD animals showed higher values ​​in the first 15 minutes than the CTLanimals. The WD-VD animals presented normal values ​​of the area under the curve, in relationto the WD. Vit D supplementation showed that there is a relationship between increasedadipose tissue and circulating vitamin D levels. Supplementation of VD3 attenuated hepaticsteatosis.

The effect of vit D3 deficiency on increased incidence of convulsion in epileptic patients

Epilepsy is a common neurological disorder affecting all age groups We sought to assess the longitudinal effect of antiepileptic drug on serum 25-hydroxyvitamin D [25(OH)D], with recurrent attack of epileptic fits. The study consisted of two parallel, 1-year, prospective, randomized, dose-ranging trials conducted in two groups of ambulatory patients, for 46 patients based on clinical presentation of the patient together with confirmed diagnosis by EEG. The patients improved when maintenance dose of Vit D3 with daily taken to restore the normal level, with measurements for all patient 95 % of patient recovered from an epileptic fits with increase the level of Vit D3 to the normal value. In conclusions, majority of the patients should be treated with an escalating regimen of vitamin D, with doses varying between 400 and 15,000 IU/day.

Evaluating the Feasibility of Pro-Neurotensin and 25-Hydroxyvitamin D3 as Possible Indicators for Type 2 Diabetes Mellitus and Its Complications.

(1) Background: Type 2 diabetes mellitus (T2DM) and metabolic syndrome are associated with decreased vitamin D. In contrast, high pro-neurotensin (pro-NT) levels are linked with an increased risk of T2DM and cardiovascular disease. We aimed to determine the validity of pro-NT and 25-dihydroxy vitamin D3 levels as predictors for T2DM complications; (2) Methods: One hundred T2DM, and one hundred healthy volunteers participated in this case-control study. Their Pro-NT and 25-hydroxyvitamin D3 levels were evaluated using the ELISA technique; (3) Results: Pro-NT and 25 (OH) vitamin D3 have significant validity and accuracy in T2DM prediction, 84.5%, and 90.5%, respectively (p = 0.001). At a value of <29.5, 25-Hydroxy vitamin D3 showed 88% sensitivity and 93% specificity in predicting T2DM. At a value of >124 Pmol/L, Pro-NT showed 81% sensitivity and 88% specificity in predicting T2DM. At a value of 16.5, 25-Hydroxy vitamin D3 had 78.4% sensitivity and 68.3% specificity in predicting T2DM complications. At a value of >158 pmol/L, Pro-NT predicted T2DM complications with 67.6% sensitivity and 56.0% specificity; (4) Conclusions: 25 (OH) Vit D3 and Pro-NT could identify T2DM patients and predict T2DM complications. More extensive research is required to adequately validate this novel perspective with a large population study.

Bone healing efficacy of Lakshagrishtiksheeradi churna over Calcium +Vit D3 in Avrana Kanda Bhagna (Closed fractures of long bones) - A Randomized controlled clinical trial

Background: Delayed bone healing or non-union of fractures owns high rate of complications, morbidity and mortality. It possesses enormous burden to both patients and healthcare system. Till now there is no proven molecule which could enhance the process of bone healing. Hence, time tested Lakshagrishtiksheeradi churna, an Ayurvedic formulation is explored for its efficacy in the management of Avrana Kanda Bhagna. Objective: To Evaluate Bone healing efficacy of Lakshagrishtiksheeradi churna in Avrana Kanda Bhagna. Methods: Total 30 patients meeting the inclusion criteria of Avrana Kanda Bhagna, with age group 14-50 years participated in the study. They were randomly divided into two groups. Group A received Lakshagrishtiksheeradi churna 6 grams and group B Tab Calcium 500 mg +VitD3 respectively twice a day for 30days. Assessments were done through various variables like Pain, Tenderness, Swelling and Bone callus index. Follow up visit was on 30th day and 45th day. Results: Study showed that both Lakshagrishtiksheeradi churna and Calcium + Vit D3 produced improvement in most of the variables and were comparable. However, marked improvements were seen in various variables like Pain, Tenderness, Swelling and Bone callus Index. Conclusion: Clinical efficacy showed that Lakshagrishtiksheeradi churna is safe, effective oral medication in the management of Avrana Kanda Bhagna (Closed Fractures of long bones).

Intralesional Vitamin D3 Versus Bleomycin for Difficult-to-Heal Palmoplantar Warts: A Comparative Study.

Difficult-to-heal or recalcitrant palmoplantar warts are notoriously resistant to treatment, making treatment difficult and challenging. To improve the outcome and overcome the difficulties, various treatment options have been tried, but none is gold standard. Many comparative studies have been undertaken to assess the efficacy of various drugs; however, none of them are standardized, and no single treatment is effective. Various comparative efficacy studies have been conducted but, to the best of our knowledge, no study has been conducted comparing intralesional (IL) injection (inj) vitamin D3 (Vit D3) with the chemotherapy drug IL inj Bleomycin for difficult-to-heal palmoplantar warts. We conducted a trial to evaluate the efficacy of IL inj Vit D3 versus IL inj Bleomycin in the treatment of difficult-to-heal palmoplantar warts. The purpose of this study was to compare the efficacy of IL inj vitamin D3 versus IL inj Bleomycin as biological response modifier therapy in difficult-to-heal palmoplantar warts. A cohort of 48 patients with difficult-to-heal warts were consecutively assigned to one of two groups: Group 1 IL inj Vit D3 (0.2-0.5 mL inj vitamin D3 600,000 IU solution 15 mg/mL) or Group 2 IL inj Bleomycin (0.2-0.4 mL of 1 U/mL solution) for a maximum of four treatments spaced 2 weeks apart, with a maximum of five warts treated at each visit for both groups. Warts were measured at baseline and at each subsequent visit. Wart's resolution was measured as 1-25%, 2-50%, 3-75%, and 4-100% reduction. Patients were followed-up for 3 months after treatment. All the 48 patients completed the study, with 26 receiving IL inj Vit D3 with complete resolution in 88.5%, partial resolution in 11.5%, and side effects in 6.2%. In 22 patients receiving IL inj Bleomycin, 95.5% had complete resolution, 4.5% had partial resolution, and 8.2% had side effects. Maximum resolution was observed in the third session. We found no recurrence after 3 months. IL inj Vit D3 and IL inj Bleomycin are both safe and effective in treating difficult-to-heal palmoplantar warts with better outcomes and patient satisfaction. IL Bleomycin was significantly more effective than IL Vit D3, although the difference was not statistically significant.

Parasitological and Hematological Study of Children Infected with Intestinal Parasites in Baquba City

The intestinal parasite infection is a significant health issue in developing countries, particularly in tropical and subtropical areas. About 3.7 billion individuals are thought to be affected annually, most of cases are children, including children in Iraq, and Baquba city. According to researchers, the main intestinal parasites affecting humans include Entamoeba histolytica, and Giardia lambellia. The present research was conducted to evaluate the prevalence of intestinal parasitic infections that causes serious problems among children aged (&gt;1 – 15 years old) and to investigate the relationship between parasitic infestation among children and their immunity (i.e., IgE), the levels of Vit D3, and Zinc. About 300 samples were collected from hospitalized and non-hospitalized children and 100 control. A fresh stool and blood sample were taken from each child during the period from 1st of November 2021 to 31st of May 2022. The collected samples were examined microscopically for identifying the parasite and examined for immunological and hematological parameters. The result showed a significant variation among children from different age groups, the age group (1&gt;-5) years old had the highest infection with intestinal parasites. In terms of gender, males had the highest intestinal parasitic infections than females. The levels of Vitamin D3 and Zinc decreased in infected children with intestinal parasitic comparing to the control. While IgE indicated higher levels in infected children than in the controls

Efficacy of dietary vitamin D3 and 25(OH)D3 on reproductive capacities, growth performance, immunity and bone development in pigs.

Vitamin D3 (Vit D3) and 25(OH)D3 are used as dietary sources of active vitamin D (1,25(OH)2D3) in pig husbandry. Although acting primarily on intestine, kidney and bone, their use in pig nutrition has shown a wide range of effects also in peripheral tissues. However, there is an ambiguity in the existing literature about whether the effects of Vit D3 and 25(OH)D3 differ in attributing the molecular and phenotypic outcomes in pigs. We searched Web of Science and PubMed databases concerning the efficacy of Vit D3 in comparison with 25(OH)D3 on pig physiology, i.e. reproductive capacities, growth performance, immunity and bone development. Dietary intake of Vit D3 or 25(OH)D3 did not influence the reproductive capacity of sows. Unlike Vit D3, the maternal intake of 25(OH)D3 significantly improved the growth performance of piglets, which might be attributed to maternally induced micronutrient efficiency. Consequently, even in the absence of maternal vitamin D supplementation, 25(OH)D3-fed offspring also demonstrated better growth than the offspring received Vit D3. Moreover, a similar superior impact of 25(OH)D3 was seen with respect to serum markers of innate and humoral immunity. Last but not least, supplements containing 25(OH)D3 were found to be more effective than Vit D3 to improve bone mineralisation and formation, especially in pigs receiving basal diets low in Ca and phosphorus. The insights are of particular value in determining the principal dietary source of vitamin D to achieve its optimum utilisation efficiency, nutritional benefits and therapeutic potency and to further improve animal welfare across different management types.

Long term dietary vitamin D3 supplementation impacts both microbicidal and inflammatory responses to ex-vivo Mycobacterium bovis BCG challenge in dairy calves

Vitamin D deficiency (VDD) is associated with enhanced susceptibility to multiple respiratory diseases in humans, including tuberculosis. However, the consequences of VDD for disease susceptibility in calves are unknown. Previously we developed a model to drive divergent circulating 25OHD concentrations in cattle, where animals were supplemented with vitamin D3 (vit D3) from birth to 7 months of age. Calves in the control group (Ctl) received a diet containing a standard vit D3 concentration, whereas the vit D group (VitD) received a diet with the highest vit D3 concentration allowed under EU guidelines. Here, we assessed the microbicidal activity and immunoregulatory effect of divergent 25OHD circulating levels to Mycobacterium bovis BCG challenge ex-vivo. Blood samples from Ctl and VitD calves were taken at 1-, 3- and 7-months of age. 25OHD concentrations were significantly different at 7 months (but not at 1 or 3 months) with animals from the VitD group having higher serum levels. Differences in microbicidal activity followed the same pattern, with no significant differences observed at 1 and 3 months, but at 7 months a significant increase in the percentage of bacteria killed was detected. Furthermore, analysis of the reactive oxygen species (ROS) and nitric oxide (NO) in serum showed a higher production of ROS and NO in VitD-supplemented calves. In contrast, serum concentrations of IL-1β and IL-8 were significantly lower. A similar anti-inflammatory profile was observed after gene expression analysis, with a significant downregulation of a cluster of genes including IL1B, IL1R1, CXCL1, CXCL2, CXCL5, MMP9 and COX2 and an upregulation of CXCR1, CX3CR1 and NCF1, in VitD calves after BCG challenge relative to Ctl animals. Collectively, these results suggest that dietary vit D3 boosts antimicrobial and innate immune responses and thereby could improve host anti-mycobacterial immunity.

Transcriptomic Analysis of Macrophage Polarization Protocols: Vitamin D3 or IL-4 and IL-13 Do Not Polarize THP-1 Monocytes into Reliable M2 Macrophages.

Two main types of macrophages (Mφ) include inflammatory (M1) and anti-inflammatory (M2) macrophages. These cells can be obtained in vitro by polarization of monocytic cell lines using various stimuli. Since there is currently no consensus on the best method for the acquisition of reliable M1 and M2 macrophages from the THP-1 cell line, we decided to compare three different polarization protocols at the transcriptomic level. Whole transcriptomes of Mφ polarized according to the chosen protocols were analyzed using RNA-seq. Differential expression of genes and functional enrichment for gene ontology terms were assessed. Compared with other protocols, M1 macrophages polarized using PMA (61.3 ng/mL) and IFN-γ along with LPS had the highest expression of M1-associated regulatory genes and genes for M1 cytokines and chemokines. According to the GO enrichment analysis, genes involved in defensive and inflammatory processes were differentially expressed in these Mφ. However, all three chosen protocols which use Vit D3, IL-13/IL-4, and IL-4, respectively, failed to promote the polarization of macrophages with a reliable M2 phenotype. Therefore, optimization or development of a new M2 polarization protocol is needed to achieve macrophages with a reliable anti-inflammatory phenotype.

A prospective randomized controlled study of Mycobacterium Indicus Pranii vaccine, Measles Mumps Rubella vaccine and Vitamin D3 in extragenital cutaneous warts.

Interventional, prospective, four arm randomized control. Outpatient department, Department of Dermatology, Venereology and Leprology, AIIMS Jodhpur (Rajasthan), India. Two hundred patients. The intervention administered in the groups were normal saline (A), vitamin D3 (B), MIP (C), and MMR (D). The injections were given into the largest wart at 2-weekly intervals until complete clearance or for a maximum of seven sittings. Post-treatment clearance of the injected wart and the distant wart was compared on the basis of change in wart number, percentage clearance, and mean time to complete clearance. Side effects were recorded. A total of 197 patients were recruited. The mean percentage improvement in the injected and non-injected warts was 68.4% and 66.8%, respectively. Intention to treat analysis (ITT) showed that complete clearance of lesions in injected wart occurred in placebo, vit D3 , MMR, and MIP arms in 64%, 66%, 58%, and 55% patients, respectively (p > 0.05), while in the non-injected warts in 62%, 64%, 52%, and 53%, respectively (p > 0.05). The mean time to achieve complete clearance of wart was fastest in MIP at 7.1 weeks followed by MMR at 7.2 weeks, VIT D3 at 7.4 weeks and in placebo group 7.8 weeks (p > 0.05). Side effects noted were fever, pain, erythema, and swelling which was highest in VIT D3 group (p < 0.05). The efficacy of immunotherapies was comparable to placebo with minimal side effects.

Molecular and epigenetic alterations in normal and malignant myelopoiesis in human leukemia 60 (HL60) promyelocytic cell line model.

In vitro cell line model systems are essential in supporting the research community due to their low cost, uniform culturing conditions, homogeneous biological resources, and easy experimental design to study the cause and effect of a gene or a molecule. Human leukemia 60 (HL60) is an in-vitro hematopoietic model system that has been used for decades to study normal myeloid differentiation and leukemia biology. Here, we show that IMDM supplemented with 20% FBS is an optimal culturing condition and induces effective myeloid differentiation compared with RPMI supplemented with 10% FBS when HL60 is induced with 1α,25-dihydroxyvitamin D3 (Vit D3) and all-trans retinoic acid (ATRA). The chromatin organization is compacted, and the repressive epigenetic mark H3K27me3 is enhanced upon HL60-mediated terminal differentiation. Differential gene expression analysis obtained from RNA sequencing in HL60 cells during myeloid differentiation showed the induction of pathways involved in epigenetic regulation, myeloid differentiation, and immune regulation. Using high-throughput transcriptomic data (GSE74246), we show the similarities (genes that did not satisfy |log2FC|>1 and FDR<0.05) and differences (FDR <0.05 and |log2FC|>1) between granulocyte-monocyte progenitor vs HL60 cells, Vit D3 induced monocytes (vMono) in HL60 cells vs primary monocytes (pMono), and HL60 cells vs leukemic blasts at the transcriptomic level. We found striking similarities in biological pathways between these comparisons, suggesting that the HL60 model system can be effectively used for studying myeloid differentiation and leukemic aberrations. The differences obtained could be attributed to the fact that the cellular programs of the leukemic cell line and primary cells are different. We validated several gene expression patterns for different comparisons with CD34+ cells derived from cord blood for myeloid differentiation and AML patients. In addition to the current knowledge, our study further reveals the significance of using HL60 cells as in vitro model system under optimal conditions to understand its potential as normal myeloid differentiation model as well as leukemic model at the molecular level.

Therapeutic effect of combination vitamin D3 and siponimod on remyelination and modulate microglia activation in cuprizone mouse model of multiple sclerosis.

Stimulation of remyelination is critical for the treatment of multiple sclerosis (MS) to alleviate symptoms and protect the myelin sheath from further damage. The current study aimed to investigate the possible therapeutic effects of combining vitamin D3 (Vit D3) and siponimod (Sipo) on enhancing remyelination and modulating microglia phenotypes in the cuprizone (CPZ) demyelination mouse model. The study was divided into two stages; demyelination (first 5 weeks) and remyelination (last 4 weeks). In the first 5 weeks, 85 mice were randomly divided into two groups, control (n = 20, standard rodent chow) and CPZ (n = 65, 0.3% CPZ mixed with chow for 6 weeks, followed by 3 weeks of standard rodent chow). At week 5, the CPZ group was re-divided into four groups (n = 14) for remyelination stages; untreated CPZ (0.2 ml of CMC orally), CPZ+Vit D3 (800 IU/kg Vit D3 orally), CPZ+Sipo (1.5 mg/kg Sipo orally), and CPZ+Vit D3 (800 IU/kg Vit D3) + Sipo (1.5 mg/kg Sipo orally). Various behavioral tasks were performed to evaluate motor performance. Luxol Fast Blue (LFB) staining, the expression level of myelin basic protein (MBP), and M1/M2 microglia phenotype genes were assessed in the corpus callosum (CC). The results showed that the combination of Vit D3 and Sipo improved behavioral deficits, significantly promoted remyelination, and modulated expression levels of microglia phenotype genes in the CC at early and late remyelination stages. These results demonstrate for the first time that a combination of Vit D3 and Sipo can improve the remyelination process in the cuprizone (CPZ) mouse model by attenuating the M1 microglia phenotype. This may help to improve the treatment of MS patients.

A case report of pseudohypoparathyroidism with bilateral fracture of neck of femur

A 19 year old female presented with a spontaneous onset of progressive non-traumatic b/l hip pain with inability to walk since 5 weeks. P/h/o pulmonary TB 2 years back present. 5 drug AKT taken for 9 months. Local tenderness was elicited and xray and MRI pelvis with both hips and LS spine was done which showed pathological fracture of basal neck of femur both side with severe listhesis of lumbosacral spine. Diagnosis of Pseudohypoparathyroidism was made on the basis of blood investigations which showed hypocalcaemia, hyper- phosphatemia, raised PTH, low Vit D3 level. Fixation of bilateral of neck femur with cancellus screw done to provide compression both side along with calcium and Activated Vitamin D3 supplimentation. Patient showed excellent response.

A study of Hepcidin levels and other Biochemical parameters in woman with Osteoporosis with Type 2 Diabetes Mellitus

Background: Diabetes mellitus (DM) could be regarded as a set of chronic metabolic disorders which have a common aspect of hyperglycemia. The resistance in the peripheral actions of insulin or impaired insulin secretion could be the reason hepcidin which is a peptide hormone derived from liver, in systemic iron homeostasis is an essential regulator, and its lopsided production participates in the pathogenesis of iron disorders in spectrum. Osteoporosis often accompanies many diseases like ß-thalassemia, hemochromatosis, sickle liver diseases, cell disease and hemosiderosis featured by iron overload, evidences suggest that Iron overload and iron deficiency are suggested by evidences that they affect bone in a negative way, acting straightway on the cells of the bone. Aim: The current study aims to find the direct relationship between the levels of Hepcidin, DHVD3 and other parameters in Osteoporosis with type 2 DM, in a female patient Methods: This study involved 60 subjects divided to two groups 30 female Osteoporosis with type 2 DM patients and 30 healthy controls . Over the period from November 2021 until the end of June 2021, this study was conducted. The ranges of age were (40-55) years. All diabetic patients examined by an endocrinologist in the Al-Yarmouk Teaching Hospital and Al- Mahmudiya Hospital . They were treated with oral anti-diabetic agents, mainly Metformin and Glibenclamide. The control subjects were referred to Laboratories Yarmouk Teaching Hospital, where all measurements were made. Control subjects were collected with glycemic control inclusion criteria when fasting serum glucose (FSG) &lt; 100 mg/dL and HbA1c &lt; 5.7%. BMI, Hb, hepcidin, Ferritin, Iron, DHVD3, Ca, PO4 were determined. Results: results was showed significant increase compared with control group in glycemic profile and lipid profile ,also, results showed a significant decrease compared with control group in Hb, Ferritin ,Iron , Vit D ,Ca , PO4 ,also the results showed a significant increase in hepcidin. Conclusion; By linking Ferritin, Iron vitamin D3 , Ca , PO4 deficiency and Hepcidin overload to women was diagnosed Osteoporosis with T2DM which indicated vit D3 deficiency related with hepcidin dysfunction. as an influencing factor on osteoarthritis women