cholecalciferol and Chronic-Disease

Vitamin D is a pleiotropic secosteroid yielding multiple actions in human physiology. Besides the canonical regulatory activity on bone metabolism, several non-classical actions have been described and the ability of vitamin D to partake in the regulation of the immune system is particularly interesting, though far stronger and convincing evidence has been collected in in vitro as compared to in vivo studies. Whether vitamin D is able to regulate at physiological concentrations the human immune system remains unproven to date. Consequently, it is not established if vitamin D status is a factor involved in the pathogenesis of immune-mediated diseases and if cholecalciferol supplementation acts as an adjuvant for autoimmune diseases. The development of autoimmunity is a heterogeneous process, which may involve different organs and systems with a wide range of clinical implications. In the present paper, we reviewed the current evidences regarding vitamin D role in the pathogenesis and management of different autoimmune diseases.

Topics: Autoimmune Diseases; Cholecalciferol; Chronic Disease; Humans; Vitamin D Deficiency

To provide primary care clinicians with an up-to-date and practical overview of the diagnosis and management of psoriasis.. PubMed, MEDLINE, EMBASE, and Cochrane databases were searched for relevant meta-analyses, randomized controlled trials, systematic reviews, and observational studies about the diagnosis and management of psoriasis.. Psoriasis is a chronic, multisystem inflammatory disease with predominantly skin and joint involvement. Beyond the physical dimensions of disease, psoriasis has an extensive emotional and psychosocial effect on patients, affecting social functioning and interpersonal relationships. As a disease of systemic inflammation, psoriasis is associated with multiple comorbidities, including cardiovascular disease and malignancy. The diagnosis is primarily clinical and a skin biopsy is seldom required. Depending on the severity of disease, appropriate treatment can be initiated. For mild to moderate disease, first-line treatment involves topical therapies including corticosteroids, vitamin D3 analogues, and combination products. These topical treatments are efficacious and can be safely initiated and prescribed by primary care physicians. Patients with more severe and refractory symptoms might require further evaluation by a dermatologist for systemic therapy.. Many patients with psoriasis seek initial evaluation and treatment from their primary care providers. Recognition of psoriasis, as well as its associated medical and psychiatric comorbidities, would facilitate timely diagnosis and appropriate management with effective and safe topical therapies and other medical and psychological interventions, as needed. More severe and refractory cases might warrant referral to a dermatologist for further evaluation and possible systemic therapy.

Topics: Administration, Topical; Adrenal Cortex Hormones; Biological Factors; Cholecalciferol; Chronic Disease; Cyclosporine; Dermatologic Agents; Drug Therapy, Combination; Female; Humans; Male; Methotrexate; Phototherapy; Psoriasis; Severity of Illness Index

Vitamin D deficiency is often reported in people with chronic liver diseases. Therefore, improving vitamin D status could have a beneficial effect on people with chronic liver diseases.. To assess the beneficial and harmful effects of vitamin D supplementation in people with chronic liver diseases.. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science. We also searched databases of ongoing trials and the World Health Organization International Clinical Trials Registry Platform. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. All searches were up to January 2017.. Randomised clinical trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D. We used standard methodological procedures expected by The Cochrane Collaboration. We contacted authors of the trials to ask for missing information. We conducted random-effects and fixed-effect meta-analyses. For dichotomous outcomes, we calculated risk ratios (RRs), and for continuous outcomes, we calculated mean differences (MD), both with 95% confidence intervals (CI) and Trial Sequential Analyses-adjusted CIs. We calculated Peto odds ratio (OR) for rare events. We considered risk of bias in domains to assess the risk of systematic errors. We conducted Trial Sequential Analyses to control the risk of random errors. We assessed the quality of the evidence with GRADE.. We included 15 randomised clinical trials with 1034 participants randomised. All trials had a parallel group design. Nine trials were conducted in high-income countries and six trials in middle-income countries. All trials were at high risk of bias. Six trials included participants with chronic hepatitis C, four trials included participants with liver cirrhosis, four trials included participants with non-alcoholic fatty liver disease, and one trial included liver transplant recipients. All included trials reported the baseline vitamin D status of participants. Participants in six trials had baseline 25-hydroxyvitamin D levels at or above vitamin D adequacy (20 ng/mL), while participants in the remaining nine trials were vitamin D insufficient (less than 20 ng/mL). All trials administered vitamin D orally. Mean duration of vitamin D supplementation was 0.5 years and follow-up was 0.6 years. Eleven trials (831 participants; 40% women; mean age 52 years) tested vitamin D. We are uncertain as to whether vitamin D supplements in the form of vitamin D

Topics: Administration, Oral; Calcitriol; Cause of Death; Cholecalciferol; Chronic Disease; Ergocalciferols; Female; Hepatitis C, Chronic; Humans; Hydroxycholecalciferols; Liver Cirrhosis; Liver Diseases; Liver Transplantation; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic; Vitamin D; Vitamin D Deficiency; Vitamins

Chronic plaque psoriasis is the most common type of psoriasis and is characterized by redness, thickness and scaling. First-line management is with topical treatments.. Our objective was to establish the effectiveness, tolerability and safety of topical treatments for people with chronic plaque psoriasis of the scalp, assessing placebo-controlled trials of all treatments and head-to-head trials that assessed vitamin D analogues.. As part of a Cochrane review of topical treatments for psoriasis, we systematically searched electronic databases for randomized controlled trials. The review included 26 randomized controlled trials of treatments for psoriasis of the scalp with 8020 participants. Trials used several measures to assess changes in psoriasis severity: these were combined using the standardized mean difference metric and interpreted by reporting as a six-point global improvement score.. On effectiveness grounds, very potent or potent steroid treatments should be preferred to vitamin D3 analogue with approximately an average 10% additional improvement on a six-point scale. Vitamin D3 analogue combined with potent steroid appears slightly more effective than potent steroid monotherapy (3% additional improvement on a six-point scale). Rates of withdrawal from treatment and adverse events in trials were generally low and similar to those for placebo. There remains uncertainty about the atrophic potential of corticosteroid treatments for scalp psoriasis.. Corticosteroids are more effective than vitamin D analogues and similarly tolerated. However, further research is needed to inform long-term maintenance treatment and provide appropriate safety data.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Cholecalciferol; Chronic Disease; Dermatologic Agents; Humans; Psoriasis; Randomized Controlled Trials as Topic; Scalp Dermatoses

Reduction in serum 1,25 (OH) (2)D level plays an important role in the pathophysiology of altered bone and mineral metabolism among patients with advanced stages of CKD. The use of vitamin D receptor activators (VDRA) has brought great progress in medical management of CKD-MBD. A number of observational studies have shown that the nonuse of VDRA, and low serum concentrations of 1,25 (OH) (2)D or 25 (OH) D are the predictors of poor clinical outcomes in CKD patients including dialysis patients, raising a possibility that the pleiotropic actions of vitamin D may be systemically involved in the poor survival of patients with CKD-MBD. Randomized controlled trials are needed to clarify whether or not VDRA could be beneficial in the protection of the cardiovascular system and good longevity.

Topics: Bone Diseases, Metabolic; Cardiovascular Diseases; Cholecalciferol; Chronic Disease; Ergocalciferols; Humans; Kidney Diseases; Minerals; Randomized Controlled Trials as Topic; Receptors, Calcitriol; Risk; Vitamin D

Atherosclerosis is common in patients with chronic kidney disease (CKD), and cardiovascular disease (CVD) represents a major cause of death in these patients, especially, in patients with end-stage renal disease(ESRD). The pathological features in ESRD patients are intimal atherosclerosis and medial calcific sclerosis. The important risk factors for CVD in ESRD patients are hypertension, dyslipidemia and CKD bone and mineral disorder (CKD-MBD). Atherosclerosis has been evaluated by measurements of intima-media thickness and pulse-wave velocity. Although the target blood pressure still undetermined, hypertension would be treated with renin-angiotensin system inhibitors. In addition, treatment of dyslipidemia with statins may lead to favorable CVD outcome. Finally, inhibition of vascular calcification should be important by treatment with active vitamin D and sevelamer.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atherosclerosis; Bone Diseases, Metabolic; Calcinosis; Cholecalciferol; Chronic Disease; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Kidney Failure, Chronic; Polyamines; Risk Factors; Sevelamer; Tunica Intima; Vascular Diseases

The biologically active metabolite of vitamin D, 1,25(OH)(2)D(3), affects mineral homeostasis and has numerous other diverse physiologic functions including effects on growth of cancer cells and protection against certain immune disorders. This article reviews the role of vitamin D hydroxylases in providing a tightly regulated supply of 1,25(OH)(2)D(3). The role of extrarenal 1alpha(OH)ase in placenta and macrophages is also discussed, as well as regulation of vitamin D hydroxylases in aging and chronic kidney disease. Understanding specific factors involved in regulating the hydroxylases may lead to the design of drugs that can selectively modulate the hydroxylases. The ability to alter levels of these enzymes would have therapeutic potential for the treatment of various diseases, including bone loss disorders and certain immune diseases.

Topics: Animals; Cholecalciferol; Cholestanetriol 26-Monooxygenase; Chronic Disease; Cytochrome P450 Family 2; Female; Humans; Kidney; Kidney Diseases; Liver; Macrophages; Mice; Placenta; Pregnancy; Steroid Hydroxylases; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

This is a mini-review of vitamin D(3), its active metabolites and their functioning in the central nervous system (CNS), especially in relation to nervous system pathologies and aging. The vitamin D(3) endocrine system consists of 3 active calcipherol hormones: calcidiol (25OHD(3)), 1alpha-calcitriol (1alpha,25(OH)2D(3)) and 24-calcitriol (24,25(OH)2D(3)). The impact of the calcipherol hormone system on aging, health and disease is discussed. Low serum calcidiol concentrations are associated with an increased risk of several chronic diseases including osteoporosis, cancer, diabetes, autoimmune disorders, hypertension, atherosclerosis and muscle weakness all of which can be considered aging-related diseases. The relationship of many of these diseases and aging-related changes in physiology show a U-shaped response curve to serum calcidiol concentrations. Clinical data suggest that vitamin D(3) insufficiency is associated with an increased risk of several CNS diseases, including multiple sclerosis, Alzheimer's and Parkinson's disease, seasonal affective disorder and schizophrenia. In line with this, recent animal and human studies suggest that vitamin D insufficiency is associated with abnormal development and functioning of the CNS. Overall, imbalances in the calcipherol system appear to cause abnormal function, including premature aging, of the CNS.

Topics: Aging; Aging, Premature; Animals; Calcifediol; Central Nervous System; Cholecalciferol; Chronic Disease; Ergocalciferols; Humans; Risk Factors; Vitamin D; Vitamin D Deficiency

Serum calcium levels are regulated by the action of parathyroid hormone (PTH). Major drivers of PTH hypersecretion and parathyroid cell proliferation are the hypocalcemia and hyperphosphatemia that develop in chronic kidney disease patients with secondary hyperparathyroidism (SHPT) as a result of low calcitriol levels and decreased kidney function. Increased PTH production in response to systemic hypocalcemia is mediated by the calcium-sensing receptor (CaR). Furthermore, as SHPT progresses, reduced expression of CaRs and vitamin D receptors (VDRs) in hyperplastic parathyroid glands may limit the ability of calcium and calcitriol to regulate PTH secretion. Current treatment for SHPT includes the administration of vitamin D sterols and phosphate binders. Treatment with vitamin D is initially effective, but efficacy often wanes with further disease progression. The actions of vitamin D sterols are undermined by reduced expression of VDRs in the parathyroid gland. Furthermore, the calcemic and phosphatemic actions of vitamin D mean that it has the potential to exacerbate abnormal mineral metabolism, resulting in the formation of vascular calcifications. Effective new treatments for SHPT that have a positive impact on mineral metabolism are clearly needed. Recent research shows that drugs that selectively target the CaR, calcimimetics, have the potential to meet these requirements.

Topics: Calcium; Cholecalciferol; Chronic Disease; Homeostasis; Humans; Hyperparathyroidism, Secondary; Kidney Diseases; Receptors, Calcitriol; Receptors, Calcium-Sensing

Myelodysplastic syndromes (MDS) include hemopoietic cytopenias of different origin, which are usually refractory to treatment. Therefore MDS patients should generally be treated conservatively. Transfusions of packed red cells (given in a strict regimen to minimize the risk for secondary hemochromatosis) may be sufficient to maintain a good quality of life. Indications for cytotoxic treatment include signs of progression of the disease. In patients with symptomatic cytopenias low-dose cytarabine (ara-C) should be tried. It is essential then to monitor each patient individually and to avoid fixed treatment schedules. Standard (high-dose) chemotherapy in MDS, is associated with a high mortality and a low response rate, and should be considered only in younger patients with advanced MDS. Allogeneic bone marrow transplantation (BMT) may be offered to younger MDS patients, when a suitable donor is available. Treatment with differentiation inducers has not met with expectations and should not be used outside clinical trials at the present. The use of recombinant hemopoietic growth factors (GF) seems promising. GF, like GM-CSF, G-CSF, IL-3, and erythropoietin, can be used either alone or in combinations, to support failing peripheral blood values, and decrease the risk for lethal complications. GF can also be given together with chemotherapy, in an effort to make the leukemic clonogenic cells more susceptible to cytotoxic drugs. Other treatments for MDS include: IFN-alpha and etoposide, with responses primarily in chronic myelomonocytic leukemia; hem arginate, whose role is still not clear; and corticosteroids, but only in carefully selected cases.

Topics: Antineoplastic Agents; Cholecalciferol; Chronic Disease; Hematopoietic Cell Growth Factors; Humans; Myelodysplastic Syndromes; Tretinoin

Topics: Arteriosclerosis; Cholecalciferol; Chronic Disease; Growth Hormone; Humans; Vitamin D

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Anti-Inflammatory Agents; Antineoplastic Agents; Azathioprine; Chloroquine; Cholecalciferol; Chronic Disease; Erythema Nodosum; Female; Humans; Levamisole; Lung Diseases; Lung Neoplasms; Lymphoma; Penicillamine; Sarcoidosis; Syndrome; Uveitis, Anterior

Topics: Amino Acid Sequence; Animals; Calcium; Cholecalciferol; Chronic Disease; Humans; Hydroxycholecalciferols; Hydroxylation; Hyperparathyroidism, Secondary; Kidney Diseases; Metabolic Clearance Rate; Molecular Weight; Parathyroid Hormone; Vitamin D

Topics: Biological Assay; Bone and Bones; Bone Diseases; Chemical Phenomena; Chemistry; Chemistry, Physical; Cholecalciferol; Chronic Disease; Humans; Kidney Diseases; Osteomalacia; Protein Binding; Radioimmunoassay; Research; Rickets; Vitamin D; Vitamin D Deficiency

Topics: Acute Disease; Adult; Animals; Calcitonin; Calcium; Calcium, Dietary; Cholecalciferol; Chronic Disease; Fatty Acids; Homeostasis; Humans; Hypocalcemia; Hypophysectomy; Malabsorption Syndromes; Pancreas; Pancreatic Diseases; Pancreatitis; Parathyroid Hormone; Pituitary Gland; Thyroxine

Recent meta-analyses of randomized clinical trials found that daily vitamin D3 supplementation had beneficial effects on cancer mortality, although the results are still controversial.. To examine whether vitamin D supplementation reduces the risk of relapse or death in a supgroup of patients with digestive tract cancer who were p53 immunoreactive.. This was a post hoc subgroup analysis of the AMATERASU randomized, double-blind, placebo-controlled clinical trial. This trial included patients at a single university hospital in Japan with digestive tract cancers between January 2010 and February 2018 followed up for a median (IQR) of 3.5 (2.5-5.3) years to compare the effects of vitamin D supplementation with placebo and was reported in 2019. Patients from among 417 participants in the AMATERASU trial whose residual serum samples were available were included. Data were analyzed from October 20 to November 24, 2022.. Vitamin D3 (2000 IU/d) supplementation or placebo.. The primary outcome was 5-year relapse or death. The subgroup of patients who were p53 immunoreactive was defined by positivity for anti-p53 antibodies in serum and nuclear accumulation of p53 oncosuppressor protein in more than 99% of cancer cells, which is considered a biomarker for p53 missense mutations. Anti-p53 antibody levels were measured using chemiluminescent enzyme immune assay. Immunohistochemical staining data of p53 protein in cancer tissue in pathologic specimens were obtained from a previous study and divided into 4 grades.. Among 392 patients with digestive tract cancer (mean [SD] age, 66 [10.7] years; 260 males [66.3%]), there were 37 patients with esophageal cancer (9.4%), 170 patients with gastric cancer (43.4%), 2 patients with small bowel cancer (0.5%), and 183 patients with colorectal cancer (46.7%). Serum anti-p53 antibody was detectable in 142 patients (36.2%), and p53-immunohistochemistry grade showed a positive association with serum anti-p53 antibody levels (coefficient = 0.19; P < .001). In the p53-immunoreactive subgroup (80 patients), relapse or death occurred in 9 of 54 patients (16.7%) in the vitamin D group and 14 of 26 patients (53.8%) in the placebo group; 5-year relapse-free survival (RFS) was significantly higher in the vitamin D group (13 patients [80.9%]) than the placebo group (1 patient [30.6%]; hazard ratio [HR], 0.27; 95% CI, 0.11-0.61; P = .002). This was significantly different from 272 patients in the non-p53 immunoreactive subgroup, in which vitamin D had no effect on 5-year RFS (vitamin D: 35 of 158 patients [22.2%] vs placebo: 24 of 114 patients [21.1%]; HR, 1.09; 95% CI, 0.65-1.84) (P for interaction = .005).. This study found that vitamin D supplementation reduced the risk of relapse or death in the subgroup of patients with digestive tract cancer who were p53 immunoreactive.. Identifier: UMIN000001977.

Topics: Aged; Cholecalciferol; Chronic Disease; Dietary Supplements; Gastrointestinal Neoplasms; Humans; Male; Neoplasm Recurrence, Local; Vitamin D; Vitamins

The management of psoriasis remains a challenge for dermatologist and patient. This study aimed to determine whether vitamin D. PASI did not differ between groups at any time (group F(1, 104) = 0.48, p = .49; group*time F(4, 384) = 0.26, p = .90). However, 25(OH)D increased in both groups, rendering these findings inconclusive. A significant inverse relationship existed between PASI and 25(OH)D, with elevation of 25(OH)D by up to 125 nmol/L associated with mild decreases in PASI (estimated range of decrease 0-2.6; p = .002).. A direct benefit of vitamin D

Topics: Administration, Oral; Adult; Cholecalciferol; Chronic Disease; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Linear Models; Male; Middle Aged; Placebo Effect; Psoriasis; Severity of Illness Index

The immunopathogenesis of chronic rhinosinusitis (CRS) is largely unknown, but it is thought that different inflammatory profiles are responsible for the different CRS subtypes. 25-Hydroxyvitamin-D (25-VD3) has been shown to alter inflammatory mediators in other disease processes and 25-VD3 deficiency is associated with CRS with nasal polyps (CRSwNP), but it is unknown if 25-VD3 levels impact local inflammation in CRS. This study investigated the correlation between plasma 25-VD3 and sinonasal mucus monocyte chemoattractant protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted (RANTES), and basic fibroblast growth factor (bFGF) levels in patients with CRS.. Study subjects undergoing endoscopic sinus surgery (ESS) for CRS were prospectively enrolled from January 2012 to August 2014. Control subjects included patients undergoing ESS for noninflammatory pathology. Blood and sinonasal mucus were collected at the time of ESS. Plasma 25-VD3 was measured by enzyme-linked immunosorbent assay (ELISA) and mucus levels of MCP-1, RANTES, and bFGF by cytometric bead array (CBA).. A total of 57 patients were enrolled and categorized as CRS without nasal polyps (CRSsNP) (n = 31), CRSwNP (n = 14), and controls (n = 12). No significant correlation was found between MCP-1 and 25-VD3. There was a significant negative correlation between 25-VD3 and RANTES (r = -0.612; p = 0.026) and bFGF (r = -0.578; p = 0.039) in CRSwNP patients; however, there was no significant correlation in CRSsNP patients.. This data suggests that 25-VD3 may play a role in regulation of RANTES and bFGF expression in CRSwNP. This may occur through regulation of NP fibroblasts or other immune cells. Further investigation is warranted to better elucidate the role of RANTES, bFGF, and 25-VD3 in CRSwNP.

Topics: Chemokine CCL2; Chemokine CCL5; Cholecalciferol; Chronic Disease; Endoscopy; Female; Fibroblast Growth Factor 2; Fibroblasts; Humans; Male; Middle Aged; Mucus; Nasal Polyps; Rhinitis; Sinusitis; Vitamin D; Vitamins

Observational reports have linked vitamin D with chronic urticaria, yet no randomized controlled trial has been conducted.. To determine whether high-dose vitamin D supplementation would decrease Urticaria Symptom Severity (USS) scores and medication burden in patients with chronic urticaria.. In a prospective, double-blinded, single-center study, 42 subjects with chronic urticaria were randomized to high (4,000 IU/d) or low (600 IU/d) vitamin D3 supplementation for 12 weeks. All subjects were provided with a standardized triple-drug therapy (cetirizine, ranitidine, and montelukast) and a written action plan. Data on USS scores, medication use, blood for 25-hydroxyvitamin D, and safety measurements were collected.. Triple-drug therapy decreased total USS scores by 33% in the first week. There was a further significant decrease (40%) in total USS scores in the high, but not low, vitamin D3 treatment group by week 12. Compared with low treatment, the high treatment group demonstrated a trend (P = .052) toward lower total USS scores at week 12, which was driven by significant decreases in body distribution and number of days with hives. Beneficial trends for sleep quality and pruritus scores were observed with high vitamin D3. Serum 25-hydroxyvitamin D levels increased with high vitamin D3 supplementation, but there was no correlation between 25-hydroxyvitamin D levels and USS scores. There was no difference in allergy medication use between groups. No adverse events occurred.. Add-on therapy with high-dose vitamin D3 (4,000 IU/d) could be considered a safe and potentially beneficial immunomodulator in patients with chronic urticaria.. clinicaltrials.gov Identifier: NCT01371877.

Topics: Acetates; Adult; Aged; Cetirizine; Cholecalciferol; Chronic Disease; Cyclopropanes; Dietary Supplements; Disease Progression; Female; Humans; Male; Middle Aged; Prospective Studies; Quinolines; Ranitidine; Sulfides; Urticaria; Young Adult

Many chronic heart failure (CHF) patients have low vitamin D (VitD) and high plasma renin activity (PRA), which are both associated with poor prognosis. Vitamin D may inhibit renin transcription and lower PRA. We investigated whether vitamin D3 (VitD3) supplementation lowers PRA in CHF patients.. We conducted a single-center, open-label, blinded end point trial in 101 stable CHF patients with reduced left ventricular ejection fraction. Patients were randomized to 6 weeks of 2,000 IU oral VitD3 daily or control. At baseline, mean age was 64 ± 10 years, 93% male, left ventricular ejection fraction 35% ± 8%, and 56% had VitD deficiency. The geometric mean (95% CI) of 25-hydroxyvitamin D3 increased from 48 nmol/L (43-54) at baseline to 80 nmol/L (75-87) after 6 weeks in the VitD3 treatment group and decreased from 47 nmol/L (42-53) to 44 nmol/L (39-49) in the control group (P < .001). The primary outcome PRA decreased from 6.5 ng/mL per hour (3.8-11.2) to 5.2 ng/mL per hour (2.9-9.5) in the VitD3 treatment group and increased from 4.9 ng/mL per hour (2.9-8.5) to 7.3 ng/mL per hour (4.5-11.8) in the control group (P = .002). This was paralleled by a larger decrease in plasma renin concentration in the VitD3 treatment group compared to control (P = .020). No significant changes were observed in secondary outcome parameters, including N-terminal pro-B-type natriuretic peptide natriuretic peptide and fibrosis markers.. Most CHF patients had VitD deficiency and high PRA levels. Six weeks of supplementation with 2,000 IU VitD3 increased 25-hydroxyvitamin D3 levels and decreased PRA and plasma renin concentration.

Topics: Aged; Cholecalciferol; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Renin; Single-Blind Method; Vitamin D Deficiency; Vitamins

Topics: Adolescent; Asthma; Body Mass Index; Child; Cholecalciferol; Chronic Disease; Disease Progression; Female; Follow-Up Studies; Humans; Male; Pilot Projects; Seasons; Spirometry; Vitamin D

To examine the effect of combined calcium and vitamin D3 supplementation on bone mineral density (BMD) inpatients with chronic kidney disease (CKD).. We performed a post-hoc analysis of the DECALYOS II, a 2-year randomized, double-blind, placebo-controlled study of 610 women randomized to: calcium-vitamin D3 fixed combination, calcium plus vitamin D3 separate combination, or placebo. Both active treatment groups received the same daily amount of calcium (1,200 mg) and vitamin D3 (800 IU). BMD of the distal radius was measured by single X-ray absorptiometry at baseline, 12 and 24 months.. At baseline 47.2%, 36.4% and 16.4% of the study population had an eGFR ≥ 60, 45 -59, and < 45 ml/min/1.73 m2, respectively. Both active regimens vs. placebo markedly increased serum 25-hydroxyvitamin D levels from baseline in all eGFR groups (p 0.22 for all time points).. Combined calcium and vitamin D3 supplementation was effective in reducing rate of BMD loss in women with moderate CKD.

Topics: Absorptiometry, Photon; Age Factors; Analysis of Variance; Biomarkers; Bone Density; Calcium; Chi-Square Distribution; Cholecalciferol; Chronic Disease; Dietary Supplements; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Institutionalization; Kidney Diseases; Placebos; Radius; Time Factors; Treatment Outcome; Vitamin D

Experimental-clinical study with inclusion of 50 Wistar rats with modeled parodontitis and 71 patients with chronic generalized parodontitis of different severity degree was conducted. Significance of oxidation stress in disease development and running was established in the course of the study. Disbalance of free-radical processes (FRP) in case of periodontal diseases affects oxygen stage of the oxidation stress in bigger degree and continues for a long time. In the course of experiment positive influence of cytoflavine preparation as energy-correction and antioxidant was confirmed as well as its combination with calcium-D3. In the course of comprehensive clinical study the efficacy of cytoflavine use was verified by the example of FRP correction that was accompanied by clinical picture and treatment results improvement.

Topics: Adult; Aged; Animals; Antioxidants; Calcium; Cholecalciferol; Chronic Disease; Drug Combinations; Drug Therapy, Combination; Energy Metabolism; Female; Flavin Mononucleotide; Free Radicals; Humans; Inosine Diphosphate; Male; Middle Aged; Niacinamide; Oxidative Stress; Periodontitis; Rats; Rats, Wistar; Succinates

The optimal treatment of secondary hyperparathyroidism in chronic kidney disease (CKD) is unknown.. We conducted a randomized, blinded, 3-month trial in vitamin D-deficient CKD stage 3 and 4 patients with parathyroid hormone (PTH) values above the Kidney Disease Outcomes Quality Initiative target, comparing cholecalciferol (4000 IU/d x 1 month, then 2000 IU/d; n = 22) to doxercalciferol (1 microg/d; n = 25).. There was no difference in baseline demographics or lab tests, except a slightly higher estimated GFR (eGFR) in the doxercalciferol group. There was a significant increase in vitamin D level in the cholecalciferol group (14 +/- 6 to 37 +/- 10 ng/ml; P < 0.001) but no change in the doxercalciferol group. The PTH decreased by 27% +/- 34% in the doxercalciferol group (P = 0.002) and decreased by 10% +/- 31% in the cholecalciferol group (P = 0.16), but the difference between treatments was NS (P = 0.11). Similar results were found when absolute PTH change from baseline to end point was analyzed in a repeated-measures ANOVA model. The serum calcium and urine calcium excretions were not different. Additional non-mineral-related end points, albuminuria, and BP were evaluated, and although trends were present, this did not reach significance.. This prospective, randomized trial demonstrated a within-group reduction in PTH in the doxercalciferol-treated patients but no significant difference between the doxercalciferol and cholecalciferol patients. Larger, long-term studies are needed to demonstrate efficacy of mineral-related and non-mineral-related end points and safety.

Topics: Aged; Biomarkers; Calcium; Cholecalciferol; Chronic Disease; Ergocalciferols; Female; Humans; Hyperparathyroidism, Secondary; Kidney Diseases; Male; Middle Aged; Parathyroid Hormone; Prospective Studies; Single-Blind Method; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Vitamins

Studies addressing the effects of vitamin D(3) supplementation on secondary hyperparathyroidism in patients with moderate chronic kidney disease are scarce.. Post hoc analysis of the randomized clinical trial Vitamin D, Calcium, Lyon Study II (DECALYOS II) to assess effects according to baseline estimated glomerular filtration rate (eGFR).. Multicenter, randomized, double-blinded, placebo-controlled study of 639 elderly women randomly assigned to calcium-vitamin D(3) fixed combination; calcium plus vitamin D(3) separate combination, or placebo.. Placebo or calcium (1,200 mg) and vitamin D(3) (800 IU) in fixed or separate combination.. Proportion of participants with a mean decrease in intact parathyroid hormone (iPTH) level of 30% or greater. eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation and categorized as 60 or greater, 45 to 59, and less than 45 mL/min/1.73 m(2).. 610 participants had an eGFR at baseline: 288 (47.2%), 222 (36.4%), and 100 (16.4%) were in each decreasing eGFR category. Across decreasing eGFR groups, 88%, 86%, and 89% had 25-hydroxyvitamin D (25[OH]D) levels less than 15 ng/mL at baseline. On treatment, similar improvements in the proportion of participants achieving 25(OH)D levels greater than 30 ng/mL at 6 months were seen in all kidney function groups (43%, 49%, and 41%, respectively). Active regimens versus placebo increased mean 25(OH)D levels from baseline in all eGFR groups at all times (P < 0.001 for all). The proportion with a 30% or greater decrease in iPTH level at 6 months was 50% in all eGFR groups on treatment versus 6% to 9% for placebo (P < 0.001 for all). The effects of the intervention on iPTH levels did not differ according to baseline eGFR (interaction P > 0.1 for all times).. This study included only elderly white women.. Vitamin D(3) was effective in increasing 25(OH)D and decreasing iPTH levels in patients with moderate chronic kidney disease.

Topics: Aged, 80 and over; Calcium, Dietary; Cholecalciferol; Chronic Disease; Dietary Supplements; Double-Blind Method; Female; Humans; Hyperparathyroidism, Secondary; Kidney Diseases; Parathyroid Hormone; Severity of Illness Index; Vitamins

Chronic chilblains is a common disease causing major restrictions in daily life, nevertheless little is known about effective treatment. In a literature search, we found thin evidence of three interventions: fluocinolone cream, nifedipine and vitamin D3.. We have conducted a study to assess the effect of oral administration of 2000 IU vitamin D3 per day on patients suffering from chronic chilblains.. The study was based on a self-controlled design. The study population consisted of patients with a confirmed diagnosis. Outcome measurement was the change in severity of the complaints and disability. We checked for interference by temperature and other confounders.. The size of the cohort (n = 33) was a limitation.. After correction for confounding factors, 19% of the subjects reported fewer complaints and 6% fewer disability, in both the placebo and vitamin D3 treatment groups.. Oral administration of 2000 IU vitamin D3 per day is not better than placebo in the treatment of patients with chronic chilblains.

Topics: Adolescent; Adult; Aged; Chilblains; Cholecalciferol; Chronic Disease; Female; Humans; Male; Middle Aged; Patient Compliance; Treatment Failure; Vitamins; Young Adult

Data on the efficacy and safety of long-term vitamin D supplementation in chronic kidney disease (CKD) are scarce. We assessed the effects of the 12-month vitamin D(3) treatment on mineral metabolism and calciotropic hormones in patients with CKD stages 2-4.. Eighty-seven patients (mean age 66 years, men/women 33/54) were randomized to cholecalciferol treatment with either 5,000 or 20,000 IU/week. Serum calcium, phosphate, 25(OH)D(3), 1,25(OH)(2)D(3), PTH and urinary mineral concentrations were obtained at baseline and after 4, 8 and 12 months.. The median serum mineral concentrations were normal and not changed throughout the study. The number of hypercalciuric patients slightly increased with higher dose, but no sustained rise in calciuria was present. Vitamin D insufficiency/deficiency was revealed in 72 (83%) patients at baseline and 37 (43%) at month 12. The 25(OH)D(3) levels increased more with higher dose; a rise in 1,25(OH)(2)D(3) was less impressive. The parathyroid hormone (PTH) concentrations were reduced, but the number of subjects with PTH below the lower limit for CKD stage 3 increased equally with both doses.. Vitamin D insufficiency/deficiency in CKD significantly improved after the 12-month cholecalciferol treatment, with higher dose being more effective and equally safe. Further studies of vitamin D(3) effects on bone metabolism are warranted.

Topics: Aged; Cholecalciferol; Chronic Disease; Dietary Supplements; Female; Hormones; Humans; Kidney Diseases; Male; Minerals; Vitamin D Deficiency

Hypovitaminosis D is common in Asian Indians. Physicians often prescribe 1500 mug (60 000 IU) cholecalciferol per week for 8 weeks for vitamin D deficiency in India. Its efficacy to increase serum 25-hydroxy vitamin D (25(OH)D) over short (2 months) and long (1 year) term is not known. We supplemented a group of twenty-eight apparently healthy Asian Indians detected to have low serum 25(OH)D (mean 13.5 (sd 3.0) nmol/l) on screening during January-March 2005. Serum parathyroid hormone (PTH) level was supranormal in 30 % of them. Oral supplementation included 1500 mug cholecalciferol per week and 1g elemental Ca daily for 8 weeks. Serum 25(OH)D, total Ca, inorganic P and intact (i) PTH were reassessed in twenty-three subjects (twelve females and eleven males) who had follow up at both 8 weeks and 1 year. At 8 weeks the mean 25(OH)D levels increased to 82.4 (sd 20.7) nmol/l and serum PTH normalized in all. Twenty-two of the twenty-three subjects had 25(OH)D levels>49.9 nmol/l. At 1 year, though the mean 25(OH)D level of 24.7 (sd 10.9) nmol/l was significantly higher than the baseline, all subjects were 25(OH)D deficient. Five subjects with supranormal iPTH at baseline showed recurrence of biochemical hyperparathyroidism. Thus, with 8 weeks of cholecalciferol supplementation in Asian Indians with chronic hypovitaminosis D, mean serum 25(OH)D levels would be normalized and serum PTH value would be reduced to half. However, such quick supplementation would not maintain their 25(OH)D levels in the sufficient range for 1 year. For sustained improvement in 25(OH)D levels vitamin D supplementation has to be ongoing after the initial cholecalciferol loading.

Topics: Adult; Analysis of Variance; Asian People; Biomarkers; Calcium; Cholecalciferol; Chronic Disease; Dietary Supplements; Female; Follow-Up Studies; Humans; India; Male; Parathyroid Hormone; Phosphorus; Rickets; Time Factors; Vitamin D; Vitamin D Deficiency

Although vitamin K2 has been shown to prevent prednisolone-induced loss of bone mineral density of the lumbar spine in patients with chronic glomerulonephritis, the magnitude of this effect remains to be clarified. The aim of this prospective study is to compare the protective effect of vitamin K2 with that of vitamin D3 on prednisolone-induced loss of bone mineral density in patients with chronic glomerulonephritis.. Sixty patients (28 men, 32 women) were randomly divided into 4 groups (n = 15 each group): control (group C), vitamin D3 alone (alfacalcidol, 0.5 microg/d; group D), vitamin K2 alone (menatetrenone, 45 mg/d; group K), and vitamins D3 plus K2 (group D + K). Alfacalcidol and menatetrenone therapy were started at the same time as prednisolone. Bone mineral density of the lumbar spine (L2 to L4) was determined by means of dual-energy X-ray absorptiometry, and various biochemical parameters of calcium and bone homeostasis were assessed before and at the end of week 8 of treatment.. Treatment with prednisolone alone caused loss of bone mineral density, which could be fully prevented in groups D, K, and D + K. However, marked reductions in levels of several biochemical markers of both bone formation and resorption also were observed in all groups. The preventive effect in groups K and D + K on loss of bone mineral density induced by prednisolone was similar to that in group D. The elevation in serum calcium levels observed in group D was attenuated in group D + K.. Protective effects of vitamin K2 or vitamins D3 and K2 on prednisolone-induced loss of bone mineral density are similar to that of vitamin D3.

Topics: Adolescent; Adult; Bone Density; Bone Resorption; Cholecalciferol; Chronic Disease; Female; Glomerulonephritis; Glucocorticoids; Humans; Lumbar Vertebrae; Male; Middle Aged; Parathyroid Hormone; Prednisolone; Prospective Studies; Vitamin K 2

The high impact of vitamin D on brain development and its relationship with inflammatory markers in the clinical course of psychiatric disorders have compelled researchers to investigate the potential association between vitamin D levels, C-reactive protein (CRP) levels, and the incidence of mental disorders. In the present study, we aimed to compare the serum levels of vitamin D and its related markers, including calcium, phosphorus, and parathyroid hormone (PTH), along with CRP, in 3 groups of patients with acute psychotic episodes, including schizophrenia, bipolar disorder, and methamphetamine-induced psychosis, with a standard control group of the Iranian population.. This descriptive cross-sectional study was conducted at a psychiatric hospital in Tehran, Iran, and involved a total of 185 subjects. The subjects included four groups: acute phase of schizophrenia (n = 49), acute manic episodes of bipolar disorder (n = 43), methamphetamine-induced psychotic disorder (n = 46), and control group (n = 47). Among 138 patients in acute psychotic episodes, 33 patients were in their first episode of psychosis, while 105 patients were in acute exacerbation of their chronic psychotic disorders. The Brief Psychiatric Rating Scale (BPRS) was measured by an expert attending psychiatrist for all patients. Then, serum levels of calcium, phosphorus, parathormone, vitamin D, and CRP were assessed in all study groups.. Among our 185 study subjects, it was observed that individuals with higher education levels and those who were married had a lower prevalence of mental disorders. In all patient groups, the serum levels of CRP were significantly higher, and PTH levels were significantly lower than in the control group (p < 0.001). The serum levels of calcium, phosphorus, and vitamin D were not statistically significantly different between the patient and control groups of the study. In chronic psychotic patients, CRP levels were significantly higher (p < 0.031), and vitamin D levels were significantly lower (p < 0.044) compared to first-episode psychotic patients.. This study suggests that CRP levels are significantly higher and PHT level is significantly lower in acute psychotic patients. Moreover, vitamin D levels were significantly lower in chronic psychotic patients compared to first-episode psychotic patients.

Topics: C-Reactive Protein; Calcium; Cholecalciferol; Chronic Disease; Cross-Sectional Studies; Humans; Iran; Methamphetamine; Parathyroid Hormone; Phosphorus; Psychotic Disorders; Vitamin D

Vitamin D deficiency is prevalent in patients with inflammatory bowel disease (IBD). The goal of this study was to assess the efficacy and safety of high-dose, interval cholecalciferol administration in patients with IBD receiving infliximab.. This prospective, longitudinal, open-label study enrolled pediatric and young adult patients with IBD and vitamin D deficiency. Subjects received 50,000 IU every 4 to 5 weeks (n = 11) or 100,000 IU every 6 to 8 weeks (n = 32) of oral cholecalciferol for 1 year. Dosing was directly observed and administered in conjunction with infliximab infusions. The primary endpoint was vitamin D sufficiency, defined as a 25-hydroxy-vitamin D (25-OHD) level ≥30 ng/mL.. Forty-three participants constituted the primary analysis population. 25-OHD levels reached steady-state after the third dose, and mean increases in 25-OHD levels were 8 vs. 4.5 ng/mL in the 100,000 IU vs. 50,000 IU treatment groups, respectively. Only 43.8% of patients receiving 100,000 IU and 18.2% of patients receiving 50,000 IU achieved sufficiency. There was no difference in the 25-OHD level responsiveness in patients with Crohn disease versus those with ulcerative colitis (P = 0.72). There was no correlation between 25-OHD levels and clinical disease activity in patients with Crohn disease (P = 0.85) or ulcerative colitis (P = 0.24).. Supplementation with cholecalciferol was well-tolerated and direct observation is a promising paradigm for ensuring compliance with therapy. Patients with IBD, however, appear to require high doses of cholecalciferol, with less than half of patients (37% overall) achieving vitamin D sufficiency. Additional studies are necessary to determine the optimal treatment regimens.

Topics: Child; Cholecalciferol; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Dietary Supplements; Humans; Inflammatory Bowel Diseases; Infliximab; Prospective Studies; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease, characterized by eosinophilic infiltration, T-helper type 2 (Th2-type) response, and olfactory dysfunction. A master regulator of Th2-type inflammation, thymic stromal lymphopoietin (TSLP), is important for basophil activation. TSLP-elicited basophils are a key factor in the pathogenesis of ECRS.. In order to elucidate the mechanisms of ECRS in humans, we aimed to establish a murine model of ECRS based on TSLP production in response to the topical application of MC903 (a vitamin D3 analog) and the subsequent TSLP-induced basophil activation. Histological analyses were performed to assess immune cell infiltration into the nasal mucosa and to explore the impact of eosinophilic inflammation on the olfactory epithelium. The status of Th2-type inflammation was evaluated by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA).. Eosinophils, basophils, and M2 macrophages increased significantly in the nasal mucosa of the mice treated with MC903 and ovalbumin (OVA), compared to those treated with OVA alone or the controls. Quantitative real-time PCR and ELISA revealed elevated expression of interleukin (IL)-4, IL-5, IL-13, TSLP, the chemokine CCL11, and CCL24 in the nasal mucosa of the ECRS mice. In parallel, thinned olfactory epithelium and decreased mature olfactory sensory neurons were observed in the ECRS mice.. Our model of ECRS displayed Th2-type inflammation in the sinonasal region, including both eosinophil infiltration and basophil infiltration. Additionally, olfactory epithelium turned out to be affected by eosinophilic inflammation. These features are consistent with the characteristics of the human ECRS.

Topics: Animals; Cholecalciferol; Chronic Disease; Cytokines; Disease Models, Animal; Eosinophilia; Eosinophils; Mice; Nasal Polyps; Rhinitis; Sinusitis

The present study aimed to investigate the effects of vitamin D3 (Vit D) administration on memory function, hippocampal level of amyloid-beta (Aβ), brain-derived neurotrophic factor (BDNF) and oxidative stress status in a rat model of unpredictable chronic mild stress (UCMS). Vit D was intraperitoneally administered at doses of 100, 1000, and 10,000 IU/kg. Animals were subjected to UCMS for a total period of 4 weeks. Memory function was assessed using morris water maze (MWM) and passive avoidance (PA) tests. Biochemical markers were measured to reveal the status of oxidative stress and antioxidant defense system. In addition, the levels of Aβ and BDNF were measured in hippocampal region. In the UCMS group, latency to find the platform was greater and the time spent in target quadrant (MWM test) as well as the latency to enter the dark compartment (PA test), were less than the vehicle group. Hippocampal malondialdehyde (MDA) and Aβ concentrations in the UCMS group were higher than the vehicle group. Hippocampal level of thiol and BDNF plus the activities of catalase and superoxide dismutase (SOD) were reduced in UCMS group compared to the control subjects (i.e. vehicle group). Interestingly, Vit D treatment supplementation reversed the mentioned effects of UCMS. Our findings indicated that Vit D administration improves UCMS-induced impairment of learning and memory through prevention of adverse effects on Aβ, BDNF and oxidative stress parameters.

Topics: Amyloid beta-Peptides; Animals; Brain-Derived Neurotrophic Factor; Cholecalciferol; Chronic Disease; Disease Models, Animal; Hippocampus; Injections, Intraperitoneal; Memory Disorders; Morris Water Maze Test; Oxidative Stress; Rats; Severity of Illness Index; Stress, Psychological; Superoxide Dismutase

Cerebral cavernous malformations (CCMs) are ectatic capillary-venous malformations that develop in approximately 0.5% of the population. Patients with CCMs may develop headaches, focal neurologic deficits, seizures, and hemorrhages. While symptomatic CCMs, depending upon the anatomic location, can be surgically removed, there is currently no pharmaceutical therapy to treat CCMs. Several mouse models have been developed to better understand CCM pathogenesis and test therapeutics. The most common mouse models induce a large CCM burden that is anatomically restricted to the cerebellum and contributes to lethality in the early days of life. These inducible models thus have a relatively short period for drug administration. We developed an inducible CCM3 mouse model that develops CCMs after weaning and provides a longer period for potential therapeutic intervention. Using this new model, three recently proposed CCM therapies, fasudil, tempol, vitamin D

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Acute Disease; Animals; Apoptosis Regulatory Proteins; Brain; Cholecalciferol; Chronic Disease; Cyclic N-Oxides; Disease Models, Animal; Gene Deletion; Hemangioma, Cavernous, Central Nervous System; Hemorrhage; Lipopolysaccharides; Mice, Inbred C57BL; Models, Biological; Phenotype; Spin Labels

Despite long use of antiepileptic drugs, it remains a challenge to achieve seizure control while reducing adverse effects and preventing cognitive impairment. Several lines of evidence suggest a role of vitamin D in epilepsy. So this study aimed to investigate the effect of vitamin D on epileptogenesis, cognitive dysfunction and antiepileptic activity of lamotrigine, in a rat model of chemical kindling. Rats were kindled by pentylenetetrazole injections every other day over four weeks, together with daily oral treatment by either vehicle, vitamin D, lamotrigine or combination of vitamin D and lamotrigine. The non-treated kindled rats developed generalized seizures and had poor cognitive performance in water maze, associated with prooxidative status; elevated malondialdehyde and nitric oxide with lowered glutathione levels; in brain tissues. Treatment with either vitamin D, lamotrigine or both leads to significant reduction of seizure activity score, improvement of cognitive performance, and amelioration of the disturbed oxidative stress biomarkers. These findings indicate that, vitamin D has anti-epileptic, cognitive improving and antioxidant effects, on its own and enhance the effects of lamotrigine, in a chronic model of epileptic seizures. Thus, vitamin D supplementation may be a useful addition to antiepileptic drugs improving seizure control and cognitive function in patients with epilepsy.

Topics: Animals; Anticonvulsants; Antioxidants; Cholecalciferol; Chronic Disease; Cognition; Disease Models, Animal; Drug Therapy, Combination; Epilepsy; Glutathione; Kindling, Neurologic; Lamotrigine; Male; Malondialdehyde; Maze Learning; Nitric Oxide; Nootropic Agents; Oxidative Stress; Pentylenetetrazole; Random Allocation; Rats, Wistar; Triazines

Currently vitamin D3 (VD3) or cholecalciferol is considered an immunomodulator that may be implicated in nasal polyposis (NP) pathophysiology.. This study aimed to investigate if deficiency of VD3 is associated with the presence of NP in patients with cystic fibrosis (CF) and patients with chronic rhinosinusitis (CRS).. In total, 152 adult participants were included in five phenotypic groups: CF with NP (CFwNP) (n = 27), CF without NP (CFsNP) (n = 31), CRS with NP (CRSwNP) (n = 32), CRS without NP (CRSsNP) (n = 30), and controls (n = 32). The serum levels of 25(OH)-VD3 < 20 ng/mL are considered as a deficiency, 21-29 ng/mL as insufficiency, and >30 ng/mL as sufficiency. Endoscopic and imaging staging of the mucosal disease performed with the Lund-Kennedy (LK) and Lund-Mackay (LM) scoring systems, respectively. The genotype of the patients with CF and the nasal microbial colonization of the patients with CF and patients with CRS were also recorded.. The patients with CFwNP had the lowest percentage of sufficiency in VD3 and the highest percentage in insufficiency among all the groups. The LM imaging scores were inversely correlated with the VD3 levels in both arms of the study (CF and CRS). Moreover, the LK endoscopic scores had a similar correlation in the CF groups; however, this was not the case with the CRS groups. The genotype of the patients with CF was not correlated with the VD3 serum levels. The patients with positive microbial colonization (mainly Pseudomonas and Staphylococcus aureus) had significantly lower VD3 serum levels in both the CF and CRS process.. VD3 deficiency seemed to be associated with the presence of nasal polyps in the patients with CRS and in the patients with CF in a similar manner. The lower the level of serum VD3, the more severe the mucosal disease was found in the imaging studies and the more frequent microbial colonization of the patients with CF and the patients with CRS.

Topics: Adolescent; Adult; Cholecalciferol; Chronic Disease; Cystic Fibrosis; Female; Humans; Male; Middle Aged; Nasal Polyps; Rhinitis; Sinusitis; Young Adult

Recent evidence suggests that 1α,25-dihydroxyvitamin D3 (calcitriol, VD3), the active form of vitamin D (VD), can inhibit the proliferation of microorganisms. In the present study, we conducted in vitro experiments and utilized in vivo murine models to investigate the antimalarial activity of VD3 and its analog, 22-oxacalcitriol (22-OCT), which was designed to cause less hypercalcemia than VD3. VD3 and 22-OCT treatments effectively resolved a Plasmodium chabaudi (Pc) infection in wild-type mice. Reduced parasitemia was observed during the acute phase of infection in the presence of VD3 and 22-OCT, followed by a delayed peak during the chronic stage of infection. Some anti-Pc activity was observed in VD receptor knockout (KO) mice. VD3 and 22-OCT also completely inhibited the proliferation of P. falciparum (Pf) in human red blood cells in vitro. Plasma levels of interferon (IFN)-γ in VD3-treated B10 and B6 mice were lower than those in vehicle-treated animals, and VD3 resolved a Pc infection in IFN-γ-KO mice, which greatly improved survival. These data suggest that the protective effects of VD3 are elicited through an IFN-γ-independent mechanism. Effective antiplasmodial doses of VD3 and 22-OCT resulted in a loss of body weight in mice. This loss in body weight occurred concomitantly with the development of hypercalcemia. Zoledronic acid partially attenuated VD3-induced hypercalcemia and abrogated the antiparasitic effects of VD3. This study highlights a potential therapeutic role for VD3 in the treatment of malarial infections and shows that hypercalcemia is excellent indicator of the antiplasmodial activity of VD3.

Topics: Acute Disease; Animals; Antimalarials; Body Weight; Calcitriol; Cholecalciferol; Chronic Disease; Diphosphonates; Erythrocytes; Humans; Hypercalcemia; Imidazoles; Interferon-gamma; Malaria; Mice; Mice, Inbred BALB C; Mice, Knockout; Parasitemia; Plasmodium chabaudi; Receptors, Calcitriol; Zoledronic Acid

Vitamin D plays a key role in the immune responses generated by lymphocytes and antigen-presenting cells. Decreased vitamin 25-hydroxyvitamin D (25(OH)D) levels have been implicated in several allergic disorders and association between 25(OH)D levels and chronic urticaria (CU) symptom scores has been evaluated in a few studies. This study was performed to assess the effects of vitamin D supplementation on the symptoms and quality of life scores in chronic spontaneous urticaria (CSU) and to vitamin D levels in CSU patients in comparison with controls.. Fifty-eight CSU patients and forty-five controls were included in the study. The patients were divided into two groups according to severity of the disease; as mild/moderate and severe urticaria. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured in serum of CSU patients and compared with the control groups. In patients with 25(OH)D concentrations lower than 30 µg/L, 300 000 IU/month of vitamin D3 supplementation was added to standard therapy. The clinical improvement was evaluated after 3 months with urticaria activity score (UAS4) and Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL).. Serum 25(OH)D concentration was significantly lower in CSU group compared to healthy subjects (p < 0.001). The prevalence of vitamin D deficiency (<20 (µg/L) and insufficiency (<30 µg/L) was significantly higher in CSU patients than control groups. In addition, 25(OH)D concentrations were significantly lower in both mild-moderate and severe CSU patients than those of the controls (p = 0.011 and p < 0.001, respectively). Ninety eight percent of patients (25(OH)D < 30 µg/L) were treated with vitamin D3 (300 000 IU/month) supplementation, and after 12 weeks, these patients showed significant improvements in UAS4 and CU-Q2oL scores.. This study support the contributing and beneficial effects of vitamin D in the treatment of CU. Replacement of vitamin D may provide improvement in both the severity of symptoms and the quality of life scores in these patients.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Cholecalciferol; Chronic Disease; Dietary Supplements; Female; Humans; Male; Middle Aged; Prospective Studies; Quality of Life; Surveys and Questionnaires; Urticaria; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

Vitamin D3 (VD3) is a steroid hormone with known antiproliferative properties. Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be VD3-deficient. Moreover, VD3 deficiency is associated with worse disease in patients with CRSwNP. One cell type thought to play a role in chronic rhinosinusitis (CRS) is the human sinonasal fibroblast (HSNF). The aim of this study was to investigate VD3 deficiency and HSNF proliferation in CRSwNP.. Blood and sinus tissue explants were collected at the time of surgery from patients with CRSwNP (n = 15). Control subjects (n = 12) were undergoing surgery for cerebrospinal fluid leak repair or to remove non-hormone-secreting pituitary tumors. Ex vivo HSNF proliferation was analyzed with flow cytometry using expression of fibroblast-specific protein (FSP) and the proliferation marker Ki67. Plasma levels of 25-hydroxyvitamin D3 (25VD3) were measured by enzyme-linked immunosorbent assay. In vitro analysis of HSNF proliferation after treatment with calcitriol (1,25VD3) was performed using carboxyfluorescein succinimidyl ester (CFSE) and analyzed with flow cytometry.. In CRSwNP patients there was an inverse correlation between 25VD3 and proliferating HSNFs (p = 0.0135). This correlation was not seen for control patients (p = 0.3869). In vitro analysis showed that HSNFs from patients with CRSwNP had a higher proliferation index at baseline than HSNFs from control patients (p < 0.01). When treated with 1,25VD3, there was a significant decrease in HSNF proliferation index in patients with CRSwNP (p < 0.01), but not control patients.. VD3 deficiency is associated with increased HSNF proliferation in CRSwNP. Further investigation into how HSNFs and VD3 impact CRSwNP pathophysiology is warranted.

Topics: Adult; Aged; Calcitriol; Cell Line; Cell Proliferation; Cholecalciferol; Chronic Disease; Female; Fibroblasts; Humans; Male; Middle Aged; Nasal Polyps; Paranasal Sinuses; Rhinitis; Sinusitis; Vitamin D Deficiency

Vitamin D (VD) deficiency in chronic lymphocytic leukemia (CLL) is associated with inferior prognosis, shorter time to treatment and worse overall survival. VD deficiency is the first potentially modifiable prognostic factor in CLL. Currently, however, there is a lack of studies concerning VD supplementation in CLL patients.. To evaluate the efficacy and safety of VD supplementation in patients with CLL.. A 6-month interventional study was conducted in CLL patients with lower serum 25-OH-D3 concentrations (< 30 ng/ml) than currently recommended. Patients with VD insufficiency (20-30 ng/ml) received 2000 IU of cholecalciferol/day, patients with moderate deficiency (10-19.9 ng/ml) received 4000 IU/day, and patients with severe VD deficiency (<10 ng/ml) received 6000 IU/day.. In the analyzed group of 13 CLL subjects, only 1 patient had a VD level within the optimal range (30-80 ng/ml), 7 had an insufficient concentration, 4 had moderate deficiency, and 1 had severe deficiency. Secondary hyperparathyroidism was diagnosed in 4 subjects. Cholecalciferol supplementation (mean dose of 3384 ± 1211 IU) was followed by a significant increase in 25-OH-D3 concentration (from 17.3 ± 5.8 to 41.4 ± 17.5 ng/ml; p<0.05) and decrease in PTH (p<0.05). Five patients did not achieve the recommended 25-OH-D3 concentration. Calcium level remained unchanged and no patients developed hypercalcemia.. VD replenishment is safe and can be effectively achieved by means of the employed cholecalciferol dosage in the majority of patients. However, some subjects may require higher doses to obtain the optimal level and immune function.

Topics: Aged; Cholecalciferol; Chronic Disease; Dietary Supplements; Female; Humans; Hyperparathyroidism, Secondary; Leukemia, Lymphoid; Male; Middle Aged; Patient Safety; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Recently, hepatic immaturity was cited as a possible reason for high levels of the C-3 epimer of 25-hydroxyvitamin (25(OH)D) in premature infants: however what role, if any, the liver plays in controlling epimer concentrations is unknown. This study assesses 3-epi-25-hydroxyvitamin D (3-epi-25(OH)D) levels during the course of cholecalciferol supplementation in adults with chronic liver diseases (CLD). Vitamin D metabolites were analyzed in 65 CLD patients with 25(OH)D <30 ng/mL who received 20 000 IU cholecalciferol/week for 6 months. The primary outcome assessed serum 25(OH)D and 3-epi-25(OH)D in response to supplementation. Corresponding values from 16 CLD patients with sufficient vitamin D levels receiving no supplementation were compared. The epimer was detected in all samples and at lower relative concentrations with lower vitamin D baseline status, i.e., severe vitamin D deficiency (<10 ng/mL) as compared with deficient (10-19.9 ng/mL), insufficient (20-29.9 ng/mL), or sufficient (≥30 ng/mL) vitamin D levels (2.4% vs. 4.8%, 5.2%, 5.8%, respectively; P < 0.001). Similar relative concentrations for 3-epi-25(OH)D, ranging from 4.3%-7.1% (absolute concentrations: 1.1-4.0 ng/mL; all P < 0.001), were obtained in response to cholecalciferol in all supplemented patients, regardless of inadequacy threshold. Epimer levels significantly decreased (P = 0.007) in unsupplemented patients, coinciding with decreasing serum 25(OH)D concentrations over time. No epimer differences between patients with (n = 17) or without (n = 48) cirrhosis were demonstrated. The 3-epi-25(OH)D was present in serum of all patients at comparable levels to those reported by others. Epimer levels increased linearly with increasing 25(OH)D levels after supplementation. However, no effect of cirrhosis on epimer concentrations was observed.

Topics: Biomarkers; Calcifediol; Cholecalciferol; Chronic Disease; Cohort Studies; Dietary Supplements; Female; Follow-Up Studies; Humans; Linear Models; Liver; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Molecular Conformation; Nutritional Status; Prospective Studies; Reproducibility of Results; Severity of Illness Index; Stereoisomerism; Vitamin D Deficiency

The objective of this work was to determine if specific chronic rhinosinusitis with nasal polyps (CRSwNP) populations are at risk for vitamin D3 (VD3 ) deficiency and if VD3 levels correlate with radiographic measures of disease severity or eosinophilia.. This study was a retrospective review of an academic rhinology practice. CRSwNP patients who had VD3 levels and CT scan within 6 months of each other were included. CT scans were graded using Lund-Mackay scoring (LMS) and peripheral eosinophil counts were measured. Demographic data including race, gender, age, body mass index, atopic status, and presence of asthma were collected. CRSwNP was subdivided into allergic fungal rhinosinusitis (AFRS), aspirin-exacerbated respiratory disease (AERD), and other CRSwNP. Multivariate analysis was performed to examine correlations and control for confounding factors.. Insufficient VD3 levels were found in 55% of all CRSwNP patients. VD3 correlated with African American race because nearly 80% of all African Americans had insufficient VD3 levels. Lower VD3 levels also correlated with more severe mucosal disease on CT scans as measured by LMS. There was no correlation between VD3 levels and age, gender, body mass index, atopy, asthma, or CRSwNP subtype.. VD3 insufficiency/deficiency is common in CRSwNP patients, especially those of African American race. Lower levels of VD3 are associated with worse LMS on CT. The role of VD3 in CRSwNP warrants further investigation.

Topics: Age Factors; Allergens; Antigens, Fungal; Aspirin; Black or African American; Cholecalciferol; Chronic Disease; Disease Progression; Eosinophilia; Female; Humans; Male; Nasal Polyps; Respiratory Mucosa; Retrospective Studies; Rhinitis, Allergic, Perennial; Risk; Sinusitis; Tomography, X-Ray Computed; Vitamin D Deficiency

Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D₃ has been considered a viable adjunctive therapy in IBD. However, vitamin D₃ plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D₃ supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10-/- CD4⁺ T cell transfer model of chronic colitis. High-dose vitamin D₃ supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D₃ metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D₃ supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D₃ diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D₃ group. Our data suggest that vitamin D₃, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D₃ supplementation in patients with active IBD.

Topics: Adoptive Transfer; Amphiregulin; Animal Feed; Animals; Bone and Bones; Bone Density; CD4-Positive T-Lymphocytes; Cholecalciferol; Chronic Disease; Colitis; Diet; EGF Family of Proteins; Gene Deletion; Glycoproteins; Intercellular Signaling Peptides and Proteins; Interleukin-10; Mice; Mice, Knockout; Vitamins

Dendritic cells are professional antigen presenting cells, capable of initiating Th1 or Th2 responses, and have been implicated in the pathogenesis of a number of diseases, including sinusitis. Vitamin D(3) is a steroid hormone that acts on dendritic cells in a manner similar to corticosteroids. Investigators examined whether children with allergic fungal rhinosinusitis (AFRS) or chronic rhinosinusitis with nasal polyposis (CRSwNP) were vitamin D(3) deficient and the relationship of vitamin D(3) deficiency to dendritic cell infiltrate in the sinus mucosa.. Tertiary care university hospital.. Retrospective, controlled study using samples collected from pediatric patients seen from August 2009 to July 2011.. Plasma levels of 25-hydroxy vitamin D(3) were measured by enzyme-linked immunosorbent assay in children (≤18 years old) with AFRS, CRSwNP, or CRS without nasal polyposis (CRSsNP) and in controls undergoing surgery for adenotonsillar hypertrophy. Vitamin D(3) levels were confirmed using clinical diagnostic methods for those with CRSwNP or AFRS. Tissue samples were immunohistochemically stained for the dendritic cell marker CD209 and the costimulatory molecules CD80 and CD86.. There was no difference in mean vitamin D(3) levels between control and CRSsNP, whereas mean CRSwNP and AFRS levels were both well below the minimum recommended level of 30 ng/mL and significantly lower than control and CRSsNP levels. CD209(+) dendritic cells inversely correlated with vitamin D(3) but not costimulatory molecule expression.. These studies identify that children with CRSwNP or AFRS are vitamin D(3) deficient, which may be linked to increased dendritic cell infiltrate. These results suggest a role for vitamin D(3) as a key player in the immunopathology of pediatric CRSwNP.

Topics: Adolescent; Analysis of Variance; Child; Child, Preschool; Cholecalciferol; Chronic Disease; Dendritic Cells; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Male; Mycoses; Nasal Mucosa; Nasal Polyps; Retrospective Studies; Sinusitis; Vitamin D Deficiency

Vitamin D(3) (VD(3) ) is a steroid hormone that regulates bone health and numerous aspects of immune function and may play a role in respiratory health. We hypothesized that T helper type 2 (Th2) disorders, chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic fungal rhinosinusitis (AFRS) would have VD(3) deficiencies, resulting in increased mature dendritic cells (DCs) and bone erosion. We conducted a retrospective study examining VD(3) levels in patients with AFRS (n = 14), CRSwNP (n = 9), chronic rhinosinusitis without nasal polyps (CRSsNP) (n = 20) and cerebrospinal fluid leak repair (non-diseased controls) (n = 14) at time of surgery. Circulating immune cell levels were determined by immunostaining and flow cytometric analysis. Plasma VD(3) and immune regulatory factors (granulocyte-macrophage colony-stimulating factor and prostaglandin E(2) ) were measured by enzyme-linked immunosorbent assay. It was observed that CRSwNP and AFRS demonstrated increased circulating DCs, while chronic rhinosinusitis without nasal polyps displayed increased circulating macrophages. CRSwNP and AFRS were to found to have insufficient levels of VD(3) which correlated inversely with circulating numbers of mature DCs, DC regulatory factors and bone erosion. CRSsNP displayed no change in circulating DC numbers or VD(3) status compared to control, but did display increased numbers of circulating macrophages that was independent of VD(3) status. Lastly, VD(3) deficiency was associated with more severe bone erosion. Taken together, these results suggest support a role for VD(3) as a key player in the immunopathology of CRSwNP and AFRS.

Topics: Blood Circulation; Bone Remodeling; Cell Count; Cells, Cultured; Cholecalciferol; Chronic Disease; Dendritic Cells; Fungi; Humans; Macrophages; Nasal Polyps; Rhinitis; Rhinitis, Allergic, Perennial; Sinusitis; Th1-Th2 Balance

Vitamin D is important for bone metabolism and neuromuscular function. While a routine dosage is often proposed in osteoporotic patients, it is not so evident in rheumatology outpatients where it has been shown that the prevalence of hypovitaminosis D is high. The aim of the current study was to systematically evaluate the vitamin D status in our outpatient rheumatology population to define the severity of the problem according to rheumatologic diseases. During November 2009, all patients were offered a screening test for 25-OH vitamin D levels and categorised as deficient (<10 µg/l [ng/ml] [25 nmol/l]), insufficient (10 µg/l to 30 µg/l [25 to 75 nmol/l]) or normal (>30 µg/l [75 nmol/l]). A total of 272 patients were included. The mean 25-OH vitamin D level was 21 µg/l (range 1.5 to 45.9). A total of 20 patients had vitamin D deficiency, 215 patients had an insufficiency and 37 patients had normal results. In the group of patients with osteoporosis mean level of 25-OH vitamin D was 25 µg/l and 31% had normal results. In patients with inflammatory rheumatic diseases (N = 219), the mean level of 25-OH vitamin D was 20.5 µg/l, and only 12% had normal 25-OH vitamin D levels. In the small group of patients with degenerative disease (N = 33), the mean level of 25-OH vitamin D was 21.8 µg/l, and 21% had normal results. Insufficiency and deficiency were even seen in 38% of the patients who were taking supplements. These results confirm that hypovitaminosis D is highly prevalent in an outpatient population of rheumatology patients, affecting 86% of subjects. Despite oral supplementation (taken in 38% of our population), only a quarter of those on oral supplementation attained normal values of 25-OH vitamin D.

Topics: Adult; Aged; Aged, 80 and over; Cholecalciferol; Chronic Disease; Cross-Sectional Studies; Dietary Supplements; Female; Humans; Low Back Pain; Lupus Erythematosus, Systemic; Male; Middle Aged; Osteoporosis; Prevalence; Rheumatic Diseases; Switzerland; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency is highly prevalent in chronic kidney disease. The aim of this study was to evaluate the effects of oral cholecalciferol supplementation on mineral metabolism, inflammation, and cardiac dimension parameters in long-term hemodialysis (HD) patients.. This 1-year prospective study included 158 HD patients. Serum levels of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], intact parathyroid hormone, and plasma brain natriuretic peptide as well as circulating bone metabolism and inflammation parameters were measured before and after supplementation. Baseline 25(OH)D and 1,25(OH)(2)D levels were measured twice (end of winter and of summer, respectively). Therapy with paricalcitol, sevelamer, and darbepoietin was evaluated.. There was an increase in serum 25(OH)D and 1,25(OH)(2)D levels after supplementation. Conversely, serum calcium, phosphorus, and intact parathyroid hormone were decreased. There was a reduction in the dosage and in the number of patients who were treated with paricalcitol and sevelamer. Darbepoietin use was also reduced, with no modification of hemoglobin values. Serum albumin increased and C-reactive protein decreased during the study. Brain natriuretic peptide levels and left ventricular mass index were significantly reduced at the end of the supplementation.. Oral cholecalciferol supplementation in HD patients seems to be an easy and cost-effective therapeutic measure. It allows reduction of vitamin D deficiency, better control of mineral metabolism with less use of active vitamin D, attenuation of inflammation, reduced dosing of erythropoiesis-stimulating agents, and possibly improvement of cardiac dysfunction.

Topics: Administration, Oral; Aged; Biomarkers; Bone Density Conservation Agents; Bone Remodeling; C-Reactive Protein; Calcitriol; Calcium; Chelating Agents; Cholecalciferol; Chronic Disease; Darbepoetin alfa; Dietary Supplements; Ergocalciferols; Erythropoietin; Female; Hematinics; Humans; Hypertrophy, Left Ventricular; Inflammation Mediators; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Parathyroid Hormone; Phosphorus; Polyamines; Prospective Studies; Renal Dialysis; Serum Albumin; Sevelamer; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Vitamins

Topics: Cholecalciferol; Chronic Disease; Dietary Supplements; Dose-Response Relationship, Drug; Ergocalciferols; Health Knowledge, Attitudes, Practice; Humans; Vitamin D Deficiency; Vitamins

Topics: Accidental Falls; Aged; Bone Density Conservation Agents; Cholecalciferol; Chronic Disease; Drug Administration Schedule; Female; Fractures, Bone; Humans; Randomized Controlled Trials as Topic; Risk; Treatment Outcome

Vitamin D insufficiency is common in patients with chronic kidney disease (CKD) and may contribute to mineral bone disease. In a prospective interventional study, we estimated the prevalence of vitamin D insufficiency (serum 25-hydroxyvitamin D3 [25OHD] < 30 ng/ml), and examined the effect of high-dose (600,000 IU) cholecalciferol supplementation after 6 weeks on serum 25OHD and parathyroid hormone (PTH) levels in children with CKD stages 2-4. Forty-two children (86% boys) with a mean age of 7.7 ± 3.8 (range 2--5) years were studied. Thirty-seven children (82.1%) had vitamin D insufficiency; 18 (42.8%) had 25OHD < 16 ng/ml. The median 25OHD increased significantly from 16.7 (95% CI 11.3, 19.8) to 46.2 (34.5, 44.6) ng/ml in patients with vitamin D insufficiency (P <0.001). The median PTH decreased significantly from 51.3 (95% CI 46.7, 71.5) to 37.1 (29.0, 54.6) pg/ml (P = 0.003). Nineteen patients (47.5%) had >30% reduction in the PTH after supplementation. Serum calcium, phosphorus, and estimated GFR did not change significantly. We conclude that vitamin D insufficiency is highly prevalent in children with CKD stages 2-4. High-dose cholecalciferol is safe and effective in correcting vitamin D insufficiency and results in a significant reduction in PTH levels in vitamin D-insufficient children.

Topics: Adolescent; Biomarkers; Calcifediol; Child; Child, Preschool; Cholecalciferol; Chronic Disease; Female; Humans; Hyperparathyroidism, Secondary; India; Kidney Diseases; Male; Parathyroid Hormone; Prevalence; Prospective Studies; Time Factors; Treatment Outcome; Vitamin D Deficiency; Vitamins

Various complications consequent on disordered calcium and phosphate homeostasis occur frequently in chronic kidney disease (CKD) patients. Particularly, vascular calcification has high morbidity and mortality rates. There is a clear need for a better CKD model to examine various aspects of this disordered homeostasis.. Oral dosing with adenine induced CKD in rats in only 10 days. Serum calcium, phosphate and parathyroid hormone were measured and calcification in aorta was assessed histologically. The effects of varying phosphorus content of diet or treatment with phosphate binders or active vitamin D(3) on these parameters were examined.. After adenine dosing, significant hyperphosphatemia, hypocalcemia and secondary hyperparathyroidism (2HPT) were observed during the experimental period of 15 weeks. Aortic calcification was detected in only some of the animals even at 15 weeks (approximately 40%). Treatment with vitamin D(3) for 18 days, even at a low dose (100 ng x kg(-1), 3-4 times week(-1), p.o), caused aortic calcification in all animals and increases in serum calcium levels up to the normal range. The vitamin D(3)-induced calcification was significantly inhibited by phosphate binders which lowered serum phosphate levels and the calcium x phosphate product, although serum calcium levels were elevated.. These data suggest that rats dosed orally with adenine provide a more useful model for analysing calcium/phosphate homeostasis in severe CKD. Controlling serum calcium/phosphate levels with phosphate binders may be better than vitamin D(3) treatment in hyperphosphatemia and 2HPT, to avoid vascular calcification.

Topics: Adenine; Animals; Aortic Diseases; Biomarkers; Blood Urea Nitrogen; Calcinosis; Calcium; Calcium Carbonate; Chelating Agents; Cholecalciferol; Chronic Disease; Creatinine; Disease Models, Animal; Disease Progression; Hyperparathyroidism, Secondary; Hyperphosphatemia; Hypocalcemia; Kidney Diseases; Male; Parathyroid Hormone; Phosphates; Polyamines; Rats; Rats, Wistar; Sevelamer; Severity of Illness Index; Time Factors

Chronic renal failure has been referred to as a state of cellular calcium toxicity. The aim of this study was to investigate the status of free cytosolic calcium ([Ca(2+)](i)), intracellular calcium reserves and the capacitative calcium entry in peripheral blood mononuclear cells (PBMCs) of early-stage chronic kidney disease (CKD) patients, and to determine the effect of vitamin D(3) supplementation on these parameters.. The study involved 44 patients with CKD stages 2-3; 27 of them were treated with cholecalciferol (5000 IU/week) for 12 months. [Ca(2+)](i) was measured using Fluo-3 AM fluorimetry. Intracellular calcium reserves were emptied by the application of thapsigargin (Tg), a specific inhibitor of endoplasmic reticulum Ca(2+)-ATPase. 2-Aminoethyl-diphenyl borate (2APB) was used to examine the capacitative calcium entry.. [Ca(2+)](i) of CKD patients was substantially higher in comparison with healthy subjects: 123 (115-127) versus 102 (98-103) nmol/l, P < 0.001. The calcium concentration of Tg-sensitive stores and the capacitative calcium entry were also significantly increased in CKD patients. After the 12-month vitamin D(3) supplementation, there was a marked decrease in [Ca(2+)](i) [105 (103-112) nmol/l, P < 0.001 versus baseline], independently of the increase in 25(OH)D(3) or the decrease in PTH levels. No significant changes in intracellular calcium reserves and the capacitative calcium entry were found.. Our results demonstrate that (1) [Ca(2+)](i), intracellular calcium stores and the capacitative calcium entry were significantly increased already in early stages of CKD; (2) long-term vitamin D(3) supplementation normalized [Ca(2+)](i) without any effect on intracellular calcium reserves or the capacitative calcium entry.

Topics: Adult; Aged; Calcium; Cholecalciferol; Chronic Disease; Dietary Supplements; Homeostasis; Humans; Kidney Diseases; Middle Aged; Receptors, Purinergic P2; Receptors, Purinergic P2X7

There are still too few conclusive reports about conspicuous vitamin D deficiency in patients with chronic pancreatitis, or any connection of the deficiency to the severity of the disease. Between October 1999 and September 2000, we investigated 42 patients at an average age of 53 years, suffering from chronic pancreatits, as well as 20 healthy male controls at an average age of 49 years. Serum levels of D3 vitamins, 1,25-(OH)2-vitamin D3 and 25-(OH)-vitamin D3, as well as the concentration of fecal elastase 1 were determined in patients and controls. Furthermore, the severity of chronic pancreatitis in patients was determined via endoscopic retrograde cholangiopancreatography (ERCP) into 3 grades, based on the Cambridge classification. Elastase 1 in feces revealed sensitivities of 14%, 87%, and 95% for Cambridge-grades I, II, and III, respectively, and correlated significantly with this classification of severity of chronic pancreatitis (P < 0.01). In patients with Cambridge-grade II and III 1,25-(OH)2-D3 was markedly decreased (26.7 +/- 7.7 pg/ml and 27.6 +/- 9.0 pg/ml) compared to those with Cambridge-grade I (38.0 +/- 10.5 pg/ml; between I and II P = 0.027, between I and III P = 0.033). 25-(OH)-D-3 did not differ significantly within the various Cambridge-grade groups (P = 0.07). Nevertheless, vitamin D3 and fecal elastase 1 in patients correlated significantly (P < 0.01) and, compared to controls, both were extremely low (means in patients: fecal elastase 1 140.7 +/- 75.7 microg/g, 1,25-(OH)2-D3 29.9 +/- 9.5 pg/ml, 25-(OH)-D3 26.7 +/- 9.7 nmol/liter; controls: fecal elastase 1 694.9 +/- 138.6 microg/g, 1,25-(OH)2-D3 67.5 +/- 4.3 pg/ml, 25-(OH)-D3 69.5 +/- 13.5 nmol/liter). The amounts of both D3 vitamins in patients were significantly lower when the content of fecal elastase 1 was under 200 microg/g compared to the others [for 1,25-(OH)2-D3 P < 0.01, for 25-(OH)-D3 P < 0.05]. Therefore, ERCP and fecal elastase 1 verify the severity grade of a chronic pancreatitis, and thus show a vitamin D3 deficiency, depending on the progress of the disease. There seems to be a connection between inflammatory pancreas destruction (Cambridge classification), exocrine insufficiency (fecal elastase 1), and perhaps even the characteristics of sterol-binding of pancreatic elastase 1, which seems to be relevant for vitamin D supply.

Topics: Adult; Calcifediol; Calcitriol; Case-Control Studies; Cholangiopancreatography, Endoscopic Retrograde; Cholecalciferol; Chronic Disease; Feces; Humans; Male; Middle Aged; Pancreatic Elastase; Pancreatitis; Severity of Illness Index

Patients with chronic liver disease (CLD) have an increased prevalence of osteoporosis. The aim of this study was to evaluate prospectively the rate of bone loss and potential predictors of increased bone loss in a cohort of patients with CLD.. Bone mineral density (BMD) was measured at baseline and at follow-up by dual-energy X-ray absorptiometry at the lumbar spine and the femoral neck.. Forty-three patients (31 female, 12 male) were available for a second measurement of BMD, with a median of 25 months (range 18-41) between the measurements. Mean annual bone loss at the lumbar spine and the femoral neck, respectively, was 0.6 +/- 2.0% and 1.5 +/- 2.4% in females and 0.8 +/- 1.9% and 2.9 +/- 2.0% in males. The BMD Z score decreased significantly over time at the femoral neck (P = 0.005 and P = 0.02 for females and males, respectively). Bone loss was increased significantly at the lumbar spine in patients classified as Child-Pugh B + C compared with those classified as Child-Pugh A (P = 0.04). Serum levels of bilirubin correlated independently and positively, and 25-hydroxy vitamin D3 levels negatively, with bone loss at the femoral neck.. Patients with CLD have increased bone loss at the femoral neck. Advanced liver disease is associated with increased bone loss, and hyperbilirubinaemia and low levels of vitamin D3 are predictors of increased bone loss.

Topics: Adult; Aged; Aged, 80 and over; Bone Density; Cholecalciferol; Chronic Disease; Female; Femur Neck; Humans; Hyperbilirubinemia; Liver Diseases; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Prospective Studies

Chronic pancreatitis is a longlasting inflammatory disease manifested clinically in the advanced stage by malabsorption syndrome. Its manifestations include also changes in the calcium metabolism and the occurrence of osteoporosis and osteomalacia or their combination. The objective of the study was to assess the vitamin D3 blood concentration in patients with chronic pancreatitis. The group comprised 15 patients (8 men and 7 women), median age 45.0 years. The authors found a significantly reduced serum concentration of vitamin D3 (p < 0.01) in patients with chronic pancreatitis. They assume that vitamin D deficiency is one of the decisive causes of bone complications in prolonged pancreatitis. Supplementation with vitamin D or its metabolites is then a necessary part of preventive and therapeutic provisions.

Topics: Adult; Aged; Cholecalciferol; Chronic Disease; Female; Humans; Male; Middle Aged; Osteomalacia; Osteoporosis; Pancreatitis; Vitamin D Deficiency

Extracellular fluid calcium is a tightly controlled variable. Hypoparathyroid state may result in profound calcium imbalance and moderate to severe hypocalcaemia. During 1974-89, 108 cases of hypoparathyroidism (97 post-surgical and 11 idiopathic) were seen. In the post-thyroidectomy group, 83 cases (85%) presented with acute transient hypocalcaemia with spontaneous recovery within 7-10 days. Chronic hypoparathyroidism was seen in 25 cases (14 post-surgical and 11 idiopathic). Convulsions resembling epileptic fits were seen in 9 cases (36%). Pseudopapilloedema was seen in three cases presenting with fits. The administration of phenobarbitone and dilantin aggravated convulsions in 9 patients. The other manifestations were psychiatric illness, cataract and calcification of basal ganglion. Biochemical findings included persistent hypocalcaemia with normal or raised serum phosphorus and lowered daily urinary excretion of calcium. Twenty three of 25 chronic hypoparathyroid cases were treated with vitamin D3 (1-3 mg/day) and calcium supplements (600-1000 mg/day)while 1 alfa-calcidol or calcitriol was used in two patients. Four patients receiving treatment with vitamin D3 developed transient hypercalcaemia with raised plasma levels of 25 hydroxy-vitamin D3. They responded to a reduction in dosage of vitamin D3. One patient was later changed over to 1-alfa-calcidol and another to calcitriol.

Topics: Acute Disease; Adolescent; Adult; Aged; Calcium, Dietary; Child; Cholecalciferol; Chronic Disease; Humans; Hydroxycholecalciferols; Hypocalcemia; Hypoparathyroidism; Middle Aged

We compared the absorption of cholecalciferol and 25-hydroxycholecalciferol in normal subjects and in patients with mild and severe cholestatic liver disease. 3H-cholecalciferol and 3H-25-hydroxycholecalciferol were given orally and serial blood samples were drawn for measurement of the serum level of radiolabeled vitamin. Absorption of 25-hydroxycholecalciferol peaked earlier and was greater than absorption of cholecalciferol at all times in all three groups. Patients with mild cholestasis (normal bilirubin and fecal fat excretion) absorbed both forms of the vitamin normally. Those with severe cholestasis (jaundice and steatorrhea) had minimal absorption of cholecalciferol but relatively preserved absorption of 25-hydroxycholecalciferol. Absorption of cholecalciferol and 25-hydroxycholecalciferol was inversely related to fecal fat excretion. The superior absorption of 25-hydroxycholecalciferol may partly explain its greater efficacy in oral treatment of vitamin D deficiency in patients with severe cholestasis.

Topics: Adult; Calcifediol; Cholangitis; Cholecalciferol; Chronic Disease; Female; Humans; Intestinal Absorption; Liver Cirrhosis, Biliary; Male; Middle Aged; Sclerosis

The reported coincidence of primary hyperparathyroidism and cholelithiasis led us to investigate the effects of acute and chronic hypercalcemia on bile secretion in cats. Acute hypercalcemia (6-7 mmol/liter) was induced by an intravenous calcium infusion. Chronic hypercalcemia (3-4 mmol/liter) was induced and maintained for 8-10 weeks by treatment with subcutaneous vitamin D3, oral dihydrotachysterol, and feeding a calcium-rich diet. Bile secretion was then studied in acute experiments. We found that calcium concentrations in serum and hepatic bile were similar during all experimental normo- or hypercalcemic conditions (y = 1.12x - 0.85; r = 0.76). Biliary volume outputs were significantly decreased during both acute (P less than 0.002) and chronic (P less than 0.05) hypercalcemia compared with normocalcemic controls. Acute hypercalcemia also decreased total bile acid outputs (P less than 0.05), but had no effect on biliary bile acid concentrations. The inhibitory effect of acute hypercalcemia on biliary fluid and bile acid secretion was dose dependent and not antagonized by atropine. These findings suggest that calcium is secreted in hepatic bile at similar concentrations as present in the serum and that elevations of serum calcium concentration inhibit biliary volume and bile acid secretion in cats. Similar effects of hypercalcemia on bile composition in humans might promote calcium salt precipitation in bile.

Topics: Acute Disease; Animals; Bile; Bile Acids and Salts; Calcium; Calcium, Dietary; Cats; Cholecalciferol; Chronic Disease; Dihydrotachysterol; Female; Hypercalcemia; Male

The effect of a vitamin D deficient (--D), vitamin D replete (150 I.U. D3 twice weekly) and normal rat diets for 4 weeks in weanling male rats on the steady-state concentration in several brain sites of dopamine (DA), norepinephrine (NE), and dihydroxyphenylacetic acid (DOPAC) was investigated. The areas of the central nervous system assayed were the brainstem, cerebellum, cerebral cortex, hypothalamus-median eminence, and striatum. The results indicate that DA content of cortex and hypothalamus significantly increased in the --D group compared to the normal diet or D replete groups. The concentrations of DOPAC and NE in the cortex of both --D and D replete rats increased significantly compared to normal diet group. Plasma calcium level was significantly lower in --D group compared to the normal diet or vitamin D replete groups.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Cerebral Cortex; Cholecalciferol; Chronic Disease; Corpus Striatum; Dopamine; Male; Norepinephrine; Phenylacetates; Rats; Rats, Inbred Strains; Vitamin D Deficiency

Topics: Bone Diseases, Metabolic; Cholecalciferol; Chronic Disease; Humans; Hydroxycholecalciferols; Liver Diseases; Osteomalacia; Osteoporosis; Vitamin D

The process of chronic hypophosphatemic vitamin D-resistant rickets--observation of two cases. With the male patient--our first case--the disease was sporadic and had not been recognized for a long time. In his early adulthood it manifested itself as Umbauzonen (pseudofractures) in the larger context of active osteomalacia. It was possible to observe the pseudofractures before and while the patient was treated with drugs. High doses of vitamin D 3 and dosage of phosphate mitigated the complains although with respect to the radiological, scintigraphic, humoral and histological findings there was only slow improvement or no improvement at all.--The patient's daughter is affected by the disease as well. In her case the pathological signs of her bones became better when treated with vitamin D 3.

Topics: Adult; Bone and Bones; Bone Diseases; Child, Preschool; Cholecalciferol; Chronic Disease; Extremities; Female; Humans; Male; Osteomalacia; Phosphates; Radiography; Thorax

To study the effects of acute and chronic cholestasis on vitamin D metabolism we investigated six cases of acute extrahepatic obstructive jaundice and eight cases of primary biliary cirrhosis (PBC) (three supplemented with vitamin D). Plasma 25-hydroxyvitamin D (25OHD) was low in the patients with PBC unsupplemented with vitamin D but normal in obstructive jaundice. None of the patients with PBC showed radiological or histological evidence of osteomalacia. In PBC, dietary intake of vitamin D was low but response to ultra-violet irradiation of the skin was normal even in those with a considerably raised serum bilirubin. Patients with PBC or obstructive jaundice had low levels of 25 hydroxyvitamin D binding protein which correlated with the serum albumin. The half-life of intravenously injected (3)H vitamin D(3) ((3)HD(3)) and the subsequent production of (3)H 25OHD were normal in all the patients with obstructive jaundice and in most with PBC. The two patients with PBC who produced less (3)H 25OHD than expected were receiving vitamin D supplements. The urinary tritium ((3)H) excretion after the injection of (3)HD(3) correlated with the serum bilirubin. After the injection of (3)H 25OHD(3) the urinary excretion of (3)H was minimal and did not correlate with the serum bilirubin, suggesting that the radioactivity appearing in the urine after the (3)H vitamin D(3) injection was associated with vitamin D metabolites other than 25OHD. Factors contributing to the low plasma 25OHD in primary biliary cirrhosis may be a low dietary intake of vitamin D, inadequate exposure to ultra-violet light, and a tendency to urinary wastage of vitamin D metabolites.

Topics: Acute Disease; Adult; Aged; Cholecalciferol; Cholestasis; Cholestasis, Extrahepatic; Chronic Disease; Ergocalciferols; Female; Half-Life; Humans; Hydroxycholecalciferols; Liver Cirrhosis, Biliary; Male; Middle Aged; Ultraviolet Therapy; Vitamin D

Topics: Adolescent; Child; Child, Preschool; Cholecalciferol; Chronic Disease; gamma-Globulins; Humans; Infant; Infant Nutritional Physiological Phenomena; Nutrition Disorders; Vitamin A; Vitamin B 12

Topics: Aerobiosis; Animals; Carbohydrate Metabolism; Carbon Dioxide; Cartilage; Cholecalciferol; Chronic Disease; Epiphyses; Glucose; Glycolysis; Lactates; Parathyroid Hormone; Pentosephosphates; Rats; Uremia

Topics: Acid Phosphatase; Animals; Cholecalciferol; Cholinesterases; Chronic Disease; Esterases; Histocytochemistry; Hypercalcemia; Male; Rats; Thyroid Gland

Topics: Azathioprine; Cholecalciferol; Chronic Disease; Deferoxamine; Glucocorticoids; Hepatitis; Humans; Liver Cirrhosis; Physical Therapy Modalities; Vitamin A; Vitamin K

Topics: Adult; Alcoholic Intoxication; Anti-Bacterial Agents; Bile Acids and Salts; Blind Loop Syndrome; Celiac Disease; Cholecalciferol; Chronic Disease; Feces; Humans; Intestinal Absorption; Intestinal Diseases; Intubation, Gastrointestinal; Jejunum; Malabsorption Syndromes; Male; Osteomalacia; Pancreatic Extracts; Pancreatitis; Tritium; Vitamin D Deficiency

When compared to that of normal animals, calcium-binding protein activity of duodenal mucosa obtained from uremic rats was decreased. There was no change in this activity after vitamin D(3), therapy. In contrast, prior treatment with 25-hydroxycholecalcijerol resulted in increased transport of calcium-45 and calcium-binding protein activity in the intestine.

Topics: Animals; Calcium; Cholecalciferol; Chronic Disease; Duodenum; Intestinal Absorption; Intestinal Mucosa; Male; Protein Binding; Rats; Stimulation, Chemical; Uremia