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Barcelona, Spain

Arboleya L.,Hospital San Agustin | Diaz-Curiel M.,Fundacion Jimenez Diaz | Del Rio L.,Centro Medico CETIR | Blanch J.,IMAS Hospital del Mar | And 8 more authors.
Aging Clinical and Experimental Research

Background and aims: Vertebral fracture (VF) is the most common complication of osteoporosis. However, more than half of all VF are asymptomatic and may go unnoticed, even in patients with osteoporosis. Our aim was to assess the prevalence of VF in postmenopausal women with osteopenic lumbar densitometry by means of vertebral morphometry, using the MorphoXpress® software. Patients and methods: This was an epidemiological, cross-sectional, multicenter study conducted among 289 postmenopausal women (>1 year of amenorrhoea), diagnosed with lumbar osteopenia (not due to chronic treatment with corticosteroids or immobilization). Vertebral deformities ≥20% were considered as VF. Results: Demographic and clinical characteristics showed mean age (±SD) 64±9 years, body mass index 27±5 kg/m 2, and time from diagnosis of 2±3 years. A total of 25% of subjects had a family history of osteoporotic fracture in first-degree relatives, and 23% had previous fragility fracture. The prevalence of VF was 50% (CI 95% 44-56), the most frequent being the dorsal wedge (34%). Previous fragility fracture was a risk factor for VF (OR 3.13, p=0.0004). A total of 76.5% of patients were receiving treatment, mainly calcium and vitamin D supplements (70%) and bisphosphonates (27%). Conclusions: MorphoXpress® revealed that 50% of postmenopausal women with osteopenic lumbar densitometry showed VF. This result is important since only 7% of all evaluated subjects had previously been diagnosed with VF. ©2010, Editrice Kurtis. Source

Ferreiro-Vera C.,University of Cordoba, Spain | Mata-Granados J.M.,University of Cordoba, Spain | Mata-Granados J.M.,IDI Group | Quesada Gomez J.M.,University of Cordoba, Spain | And 3 more authors.

The automated method developed for the determination of carotenoids uses 200 μL of serum, which was mixed with 400 μL of tetrahydrofuran, vortexed for 1 min, settled for 10 min, centrifuged for 6 min and the supernatant injected into an automatic solid-phase extraction (SPE) system for cleanup-preconcentration. A 10% water-acetonitrile mobile phase at 1.5 mL min -1 eluted the retained compounds and transferred them on-line to a reversed-phase analytical column for individual separation of the target analytes. Visible detection was performed at 450 and 460 nm. The detection limits for the target analytes were between 3 and 30 ng mL -1; the precision (expressed as relative standard deviation) ranged between 2.83 and 5.06% for repeatability and between 3.80 and 7.40% for within laboratory reproducibility. The total analysis time was 18 min. The proposed method is reliable, robust, and has an excellent potential for high-throughput use in both clinical and research laboratories. © 2011 Elsevier B.V. All rights reserved. Source

Runger T.M.,Boston University | Adami S.,Boston University | Adami S.,University of Verona | Benhamou C.-L.,Boston University | And 14 more authors.
Journal of the American Academy of Dermatology

Background: In a multicenter clinical trial in North America and Europe that tested the cathepsin K (catK) inhibitor balicatib for the treatment of osteoporosis, several patients developed hardening of the skin. Objective: We sought to characterize these observed adverse events. Methods: Patients with skin hardening were examined by a local dermatologist. All of those patients except one had at least one biopsy specimen taken from affected skin, which was read by local and two central dermatopathologists. Workup was directed for consideration of systemic scleroderma. Results: Nine patients of 709 treated with balicatib developed skin hardening and were given a diagnosis of morphea-like skin changes. No such events were observed in patients taking placebo or the lowest balicatib dose. After discontinuation of balicatib, skin changes resolved completely in 8 and partially in one patient. Limitations: Each patient was seen by a different dermatologist in 6 different countries. Conclusions: These observations are likely dose-related adverse effects of balicatib. Although catK was originally thought to be expressed only in osteoclasts, it has more recently also been found in lung and dermal fibroblasts and been implicated in the degradation of the extracellular matrix in the lung and the skin. It is therefore plausible that the observed dermal fibrosis in balicatib-treated patients is a result of impaired degradation of extracellular matrix proteins and may represent a class effect of catK inhibitors. We recommend that further exploration of catK inhibition for the treatment of osteoporosis or cancer should include monitoring for similar adverse effects. © 2010 by the American Academy of Dermatology, Inc. Source

Mata-Granados J.M.,IDI Group | Mata-Granados J.M.,University of Cordoba, Spain | Mata-Granados J.M.,Mineral Metabolism Unit | Vargas-Vasserot J.,Intensive Care Unit Hospital Reina Sofia | And 5 more authors.
Journal of Steroid Biochemistry and Molecular Biology

Vitamin D deficiency is recognized as one of the most common chronic medical conditions in the world. Vitamin deficiency has been associated with increased mortality. The aim of the study here presented was to evaluate the vitamin D endocrine system (VDES) status in healthy blood donors and critically ill patients baseline and in response to treatment during a week with two doses of 1.5mg of 25-hydroxyvitamin D3 and 2μg calcitriol (1,25(OH)2D3) IV on alternate days, by monitoring levels in serum of major vitamin D metabolites in critically ill patients. Group 1: healthy blood donors (control group) (n=92), and group 2: critically ill subjects from an intensive care unit (ICU) (n=33). Critically ill patients were divided into three groups: group A (n=12) is the control group; group B (n=11), administration PO 1,5mg of 25(OH)D3, in days 0 and 4 of treatment; and group C (n=11), administration IV of 2μg 1,25(OH)2D3 on alternate days. Baseline serum levels of vitamin D2 and 25(OH)D2 were not detected. Vitamin D3 (9.8 vs 26.0nM) (p<0.05), 25(OH)D3 (13.3 vs 52.3nM) (p<0.001), and 1,25(OH)2D3 (53.8 vs 120.5 pM) (p<0.01) serum levels were significantly lower in critically ill subjects than in healthy donors.After treatment in group B: 25OHD3 increased to 46.0±16.5ng/ml (p<0.0001) (22.2%<75nM, 11.1% <50nM). 1,25(OH)2D3 increased to 121.8±61.8pM<0.01 whereas were slightly decreased in the other groups during the study. 24,25(OH)2D3 serum levels were increased in patients treated with calcitriol 8.5±5.3 vs 24.8±16.3nM (p<0.05) while the levels kept stable in group A patients.In summary, critically ill patients have a severe vitamin D deficiency, which can be easily corrected by administration of high doses of 25OHD (PO). The VDES functional deficiency could be probably also corrected through administration of calcitriol (IV). Both treatments could produce an improvement in the general health and probably a reduction in overall mortality risk of the critically ill patients. © 2010 Elsevier Ltd. Source

Ferreiro-Vera C.,University of Cordoba, Spain | Mata-Granados J.M.,University of Cordoba, Spain | Mata-Granados J.M.,IDI Group | Mata-Granados J.M.,Mineral Metabolism Unit | And 5 more authors.
Analytical and Bioanalytical Chemistry

Inflammation is a complex cascade process involved in the pathogenesis of a number of diseases or generated as response to external or internal stimuli. Current research is focused on the development of assays for fast identification and quantitation of inflammation biomarkers. Eicosanoids are the oxidation metabolites of polyunsaturated fatty acids (mainly 20-carbon fatty acids) that play a regulation role in inflammation and, therefore, they have proved to be involved in different pathological states such as cancer, atherosclerosis, arthritis and cardiovascular or immunological diseases. Eicosanoids can be metabolized by different oxygenase enzymes to prostanoids such as prostaglandins and thromboxanes or hydroxyl fatty acids such as hydroxyeicosatetraenoic acids and hydroxyoctadecadienoic acids. A high-throughput automated approach is here presented for direct eicosanoid analysis in biofluids such as human serum and cells culture media. The approach is based on a hyphenated system composed by a solid-phase extraction workstation (Prospekt 2 unit) on-line coupled to a liquid chromatograph-triple quadrupole-tandem mass spectrometer. The detection limits for the target analytes ranged from 0.009 to 204 pg on-column, with precision between 2.65% and 7.33%, expressed as relative standard deviation. Accuracy studies with a dual-cartridge configuration resulted in recoveries between 78.6% and 100%, which validated internally the proposed approach ensuring highly efficient cleanup of proteins and salts. The method is reliable, robust and endowed with a great potential for implementation in clinical and routine laboratories. Analysis of culture media of stem cells stimulated with arachidonic acid was carried out to evaluate its incidence on the eicosanoid profile of the exometabolome. [Figure not available: see fulltext.] © 2010 Springer-Verlag. Source

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