Vitamin D Levels and Lipid Response to Atorvastatin

Adequate vitamin D levels are necessary for good vascular health. 1,25-dihydroxycholecalciferol activates CYP3A4, an enzyme of the cytochrome P450 system, which metabolizes atorvastatin to its main metabolites. The objective of this study was to evaluate the response of cholesterol and triglycerides to atorvastatin according to vitamin D levels. Sixty-three patients with acute myocardial infarction treated with low and high doses of atorvastatin were included. Levels of total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol were measured at baseline and at 12 months of follow-up. Baseline levels of 25-hydroxyvitamin D (25-OHD) were classified as deficient (<30 nmol/L), insufficient (30–50 nmol/L), and normal (>50 nmol/L). In patients with 25-OHD <30 nmol/L, there were no significant changes in levels of total cholesterol (173 ± 47 mg/dL versus 164 ± 51 mg/dL), triglycerides (151 ± 49 mg/dL versus 177 ± 94 mg/dL), and LDL cholesterol (111 ± 48 mg/dL versus 92 45 ± mg/dL); whereas patients with insufficient (30–50 nmol/L) and normal vitamin D (>50 nmol/L) had a good response to atorvastatin. We suggest that vitamin D concentrations >30 nmol/L may be required for atorvastatin to reduce lipid levels in patients with acute myocardial infarction

Clinical Study Vitamin D Levels and Lipid Response to Atorvastatin

Adequate vitamin D levels are necessary for good vascular health. 1,25-dihydroxycholecalciferol activates CYP3A4, an enzyme of the cytochrome P450 system, which metabolizes atorvastatin to its main metabolites. The objective of this study was to evaluate the response of cholesterol and triglycerides to atorvastatin according to vitamin D levels. Sixty-three patients with acute myocardial infarction treated with low and high doses of atorvastatin were included. Levels of total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol were measured at baseline and at 12 months of follow-up. Baseline levels of 25-hydroxyvitamin D (25-OHD) were classified as deficient (&lt;30 nmol/L), insufficient (30-50 nmol/L), and normal (&gt;50 nmol/L). In patients with 25-OHD &lt; 30 nmol/L, there were no significant changes in levels of total cholesterol (173 ± 47 mg/dL versus 164 ± 51 mg/dL), triglycerides (151 ± 49 mg/dL versus 177 ± 94 mg/dL), and LDL cholesterol (111 ± 48 mg/dL versus 92 45± mg/dL); whereas patients with insufficient (30-50 nmol/L) and normal vitamin D (&gt;50 nmol/L) had a good response to atorvastatin. We suggest that vitamin D concentrations &gt;30 nmol/L may be required for atorvastatin to reduce lipid levels in patients with acute myocardial infarction

Caloric test results in Paget´s disease of bone

[ES] Introducción: En la enfermedad de Paget (EP), la complicación neurológica más frecuente se relaciona con la afectación del hueso temporal a nivel intrapetroso. Los síntomas vestibulares son comunes en la enfermedad de Paget, pero se pueden pasar fácilmente por alto, por su leve intensidad. La literatura no está clara en relación con el resultado de las pruebas calóricas. El objetivo del presente estudio, es conocer si existe una mayor incidencia de alteraciones vestibulares en el grupo de pacientes con EP craneal comparándolos con pacientes con EP sin afectación craneal, así como una mayor alteración en el resultado de la prueba calórica. Material y métodos: Se trata de un estudio tipo casos-controles. La selección de pacientes se realizó de forma aleatoria. El tamaño muestral fue de 50 pacientes, 30 de ellos con EP sin afectación craneal, 13 con EP craneal sin afectación temporal y 7 con EP craneal y temporal en la gammagrafía. Resultados: Un 22% de los pacientes de la muestra presentaron historia crisis vertiginosas y sin embargo un 46 % presentaron déficit vestibular en el resultado de la prueba calórica. Conclusiones: Un elevado porcentaje de pacientes no presentó historia clínica de crisis vertiginosas, sin embargo, fue mayor el porcentaje de pacientes que presentaron alteraciones en la prueba calórica de la videonistagmografía. No se encontraron diferencias estadísticamente significativas entre los grupos con EP en el análisis del déficit vestibular. [EN] In Paget's disease, the most common neurological complication relates to the temporal bone involvement intrapetrous level. Vestibular symptoms are common in Paget's disease, but you can pass easily overlooked for its mild intensity. The literature is not clear regarding the result of caloric testing. Methods: The study comprised 50 patients, 30 patients with PD without skull involvement, 13 patients with skull involvement and without temporal involvement and 7 patients with PD with skull and temporal involvement in scintigraphy. Results: 22% of patients in the sample had history crises dizzying and yet 46% had deficits in vestibular caloric test result. Conclusions: We found no statistically significant differences between the groups in the analysis of EP vestibular deficit

Association of aromatase and estrogen receptor gene polymorphisms with hip fractures

Producción CientíficaSummary Two polymorphisms of the aromatase and estrogen receptor genes appeared to interact to influence the risk of hip fractures in women. Introduction Allelic variants of the aromatase gene have been associated with bone mineral density and vertebral fractures. Our objective was to analyze the relationship between two polymorphisms of the aromatase and estrogen receptor genes and hip fracture

Ex vivo identification and characterization of a population of CD13high CD105+ CD45− mesenchymal stem cells in human bone marrow

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.[Introduction]: Mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and multilineage differentiation. Their multipotential capacity and immunomodulatory properties have led to an increasing interest in their biological properties and therapeutic applications. Currently, the definition of MSCs relies on a combination of phenotypic, morphological and functional characteristics which are typically evaluated upon in vitro expansion, a process that may ultimately lead to modulation of the immunophenotypic, functional and/or genetic features of these cells. Therefore, at present there is great interest in providing markers and phenotypes for direct in vivo and ex vivo identification and isolation of MSCs. [Methods]: Multiparameter flow cytometry immunophenotypic studies were performed on 65 bone marrow (BM) samples for characterization of CD13high CD105+ CD45– cells. Isolation and expansion of these cells was performed in a subset of samples in parallel to the expansion of MSCs from mononuclear cells following currently established procedures. The protein expression profile of these cells was further assessed on (paired) primary and in vitro expanded BM MSCs, and their adipogenic, chondrogenic and osteogenic differentiation potential was also determined. [Results]: Our results show that the CD13high CD105+ CD45− immunophenotype defines a minor subset of cells that are systematically present ex vivo in normal/reactive BM (n = 65) and that display immunophenotypic features, plastic adherence ability, and osteogenic, adipogenic and chondrogenic differentiation capacities fully compatible with those of MSCs. In addition, we also show that in vitro expansion of these cells modulates their immunophenotypic characteristics, including changes in the expression of markers currently used for the definition of MSCs, such as CD105, CD146 and HLA-DR. [Conclusions]: BM MSCs can be identified ex vivo in normal/reactive BM, based on a robust CD13high CD105+ and CD45− immunophenotypic profile. Furthermore, in vitro expansion of these cells is associated with significant changes in the immunophenotypic profile of MSCs.This work was supported by grants from the Instituto de Salud Carlos III, FEDER, Ministry of Economy and Competitivity, Madrid, Spain (grant PI11/02399; RETICEF RD12/0043/0021; RTICC RD12/0036/0048); Fundación Ramon Areces, Madrid, Spain (grant CIVP16A1806); Fundación Científica de la Asociación Española Contra el Cáncer (AECC); Consejería de Sanidad, Gerencia Regional de Salud de Castilla y León (SACYL) (grant BIO/SA24/13) and Fundación Samuel Solórzano Barruso (University of Salamanca, Spain); CT was supported by a grant co-financed by the European Social Fund and the Junta de Castilla y León (Spain).Peer Reviewe

Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns.This study was funded by Faes Farma, S.A. and Bruno Farmaceutici S.p.A. The authors wish to thank the study participants, research staff, the secondary investigators of the Osteoferol study group, the home nursing staff (Emibet), and Faes Farma clinical research team: Paula Arranz Gutiérrez, Lorena Elgezabal González, Mariana Frau Usoz, and Iñigo Saez Riesco. Medical writing support was provided by Francisco López de Saro (Trialance SCCL), funded by Faes Farma, S.A

Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean ± standard deviation change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in patients treated with calcifediol and cholecalciferol, respectively). No relevant treatment-related safety issues were reported in any of the groups studied. These results thus confirm that calcifediol is effective, faster, and more potent than cholecalciferol in raising serum 25(OH)D levels and is a valuable option for the treatment of vitamin D deficiency

Ex vivo identification and characterization of a population of CD13high CD105+ CD45- mesenchymal stem cells in human bone marrow

Introduction: Mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and multilineage differentiation. Their multipotential capacity and immunomodulatory properties have led to an increasing interest in their biological properties and therapeutic applications. Currently, the definition of MSCs relies on a combination of phenotypic, morphological and functional characteristics which are typically evaluated upon in vitro expansion, a process that may ultimately lead to modulation of the immunophenotypic, functional and/or genetic features of these cells. Therefore, at present there is great interest in providing markers and phenotypes for direct in vivo and ex vivo identification and isolation of MSCs. Methods: Multiparameter flow cytometry immunophenotypic studies were performed on 65 bone marrow (BM) samples for characterization of CD13high CD105+ CD45- cells. Isolation and expansion of these cells was performed in a subset of samples in parallel to the expansion of MSCs from mononuclear cells following currently established procedures. The protein expre

Multidisciplinary consensus on the therapeutic recommendations for iatrogenic hyperprolactinemia secondary to antipsychotics

Hyperprolactinemia is an underappreciated/unknown adverse effects of antipsychotics. The consequences of hyperprolactinemia compromise therapeutic adherence and can be serious. We present the consensus recommendations made by a group of experts regarding the management of antipsychotic-induced hyperprolactinemia. The current consensus was developed in 3 phases: 1, review of the scientific literature; 2, subsequent round table discussion to attempt to reach a consensus among the experts; and 3, review by all of the authors of the final conclusions until reaching a complete consensus. We include recommendations on the appropriate time to act after hyperprolactinemia detection and discuss the evidence on available options: decreasing the dose of the antipsychotic drug, switching antipsychotics, adding aripiprazole, adding dopaminergic agonists, and other type of treatment. The consensus also included recommendations for some specific populations such as patients with a first psychotic episode and the pediatric-youth population, bipolar disorder, personality disorders and the elderly population