Genistein supplementation has no effects on vitamin D levels in healthy Spanish postmenopausal women.

Background: In vitro studies have shown that genistein inhibits the CYP240 enzyme, which is involved in the degradation of 1,25-dihydroxycholecalciferol and its precursor 25-hydroxycholecalciferol, and increases their plasma levels. However, no clinical studies have primarily assessed the synergistic effect of isoflavones on vitamin D levels. The aim of this study was to evaluate the possible additive effect of genistein supplementation on vitamin D levels, calcium metabolism and bone remodeling markers in healthy postmenopausal women during the spring-summer months. Patients and methods: We made a prospective, double-blind study with 150 healthy postmenopausal women that were randomized to three groups. One received placebo, another received calcium (1000 mg/day) and vitamin D (cholecalciferol, 800 U/day) and the third received calcium (1000 mg/day), vitamin D (cholecalciferol, 800 U/day) and genistein (90 mg/day). The study period was from May to September (spring-summer). Vitamin D, PTH, CTX and P1NP were determined by electrochemiluminescence at baseline and after 12 weeks. Results: Vitamin D levels increased in all groups: placebo (23±9 ng/ml vs. 29±10 ng/ml, p<0.05), calcium+vitamin D (26±10 ng/ml vs. 33±8 ng/ml, p<0.05) and calcium+vitamin D+genistein (24±9 ng/ml vs. 31±8 ng/l, p<0.05) without between-group differences. At study end, the percentage of women with vitamin D <20 ng/ml (11%) and <30 ng/ml (39%) had fallen without between-group differences. The effects on calcium metabolism and bone remodeling markers were similar between groups: rises in vitamin D were significantly linked to reductions in PTH, CTX and P1NP. Conclusion: Adding genistein to supplementation with calcium and vitamin D provided not additional changes in vitamin D levels, calcium metabolism or bone remodeling markers in healthy Spanish postmenopausal women during the spring-summer months.

A mutation in p62 protein (p. R321C), associated to Paget's disease of bone, causes a blockade of autophagy and an activation of NF-kB pathway.

Paget's disease of bone (PDB) is a bone disorder characterized by an increase in bone turnover in a disorganized way with a large increase in bone resorption followed by bone formation. The most important known genetic factor predisposing to PDB is mutation in Sequestosome1 (SQSTM1) gene. We have studied the prevalence of SQSTM1 mutations and examined genotype-phenotype correlations in a Spanish cohort of PDB patients. Also, we have characterized three PDB patients that carry the c.961C>T SQSTM1 gene mutation that it is localized in exon 6 of SQSTM1 gene and it causes the p. R321C mutation. This mutation has been reported in patients with amyotrophic lateral sclerosis and frontotemporal dementia but in our knowledge this is the first time that p62 p. R321C mutation is associated to PDB. We show that p62 p.R321C mutation could induce blockage of autophagy and cell proliferation through NF-kB pathway. These results reinforce the hypothesis of autophagy involvement in Paget's disease of bone.

The complexity of classifying ANCA-associated small-vessel vasculitis in actual clinical practice: data from a multicenter retrospective survey.

The different sets of criteria for diagnosis or classification of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) lead to numerous overlapping and reclassified diagnoses in clinical practice. We designed this study to assess the difficulties in classifying patients with AAV. As a secondary objective, different variables were tested to predict prognosis. We conducted a retrospective chart review in a Western Spain multicentre survey. A total of 115 adult patients diagnosed with AAV from 2002 to 2013 and followed for at least 3 years were included. They were classified according to (1) Chapel Hill Consensus Conference (CHCC), (2) European Medicines Agency algorithm and (3) French Vasculitis Study Group/European Vasculitis Society phenotypes. Fifty-three patients (46%) had neither distinctive histopathological data of a single AAV definition nor any surrogate markers for granulomatous inflammation and thus did not fulfill any diagnostic criteria. Ocular, ear, nose, throat, skin, and lung involvement were more frequent with proteinase 3 (PR3) antibodies, whereas peripheral neuropathy was more frequent with myeloperoxidase (MPO) antibodies. When the disease was severe at diagnosis, the HR for mortality was 10.44. When induction treatment was not given in accordance with the guidelines, the HR for mortality was 4.00. For maintenance treatment, the HR was 5.49 for mortality and 2.48 for relapse. AAV classification is difficult because many patients had neither specific clinical data nor distinctive histological features of a single CHCC definition. A structured clinical assessment of patient severity is the best tool to guide the management of AAV.

Hipocratismo digital: paciente con osteoartropatía hipertrófica y presencia de acro-osteólisis / Digital clubbing: a patient with hypertrophic osteoarthropathy and the presence of acro-osteolysis

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Estrogen receptor genes polymorphisms determine serum lipid profile in healthy postmenopausal women treated with calcium, vitamin D, and genistein.

Cardiovascular risk increases in women after menopause. Unfavorable lipid-lipoprotein changes due to a lack of estrogens may have an important role in this context. Estrogen actions are mainly mediated by their binding to two estrogen receptors (ERs) whose signaling may be conditioned by different factors. Calcium, vitamin D, and genistein, among others, cause a beneficial effect on serum lipid profile by its modulation. Some genetic factors can also determine this signal. We determined the possible additive effect of genistein on calcium and vitamin D supplementation regarding serum lipid profile changes and whether ER polymorphisms may mediate in this effect. We performed a prospective, double blind study in which women were randomized in two groups: one group received calcium and vitamin D and the other group received calcium, vitamin D and genistein. Subsequently, we studied rs9340799, rs928554, and rs4986938 ER polymorphisms in both groups. Our results showed that being a carrier of the variant allele G of rs928554 polymorphism was associated with a greater decrease in triglyceride levels and that the homozygous AA genotype of rs9340799 polymorphism was associated with a greater decrease in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels after calcium, vitamin D, and genistein supplementation. This is the first report showing an association between polymorphisms in ER genes and an improvement of the serum lipid profile after taking calcium, vitamin D, and genistein supplementation in postmenopausal women. It reinforces the hypothesis that genetic factors are crucial in ER signalling.

Influence Of Angiogenic Mediators And Bone Remodelling In Paget´s Disease Of Bone.

Paget´s disease of bone (PDB) is characterized by increased bone resorption followed by an excessive compensatory bone formation, with an abnormal bone structure with altered mechanical properties. Pagetic bone also has a higher vascularization and marrow fibrosis. Despite of pagetic bone being a highly vascularized tissue, there are no studies on the plasma levels of angiogenic mediators in the different states of the disease; moreover, the effect of PDB treatment on plasma levels of these angiogenic mediators is not very well known. The aim of this study was to analyse plasma levels of cytokines implicated in the increased bone turnover (OPG, RANKL, sclerostin) and hypervascularization (VEGF, PGF, ENG) observed in PDB and their evolution and response to zoledronic acid treatment in 70 PDB patients, 29 with an active disease measured by plasma alkaline phosphatase (ALP). Plasma ALP concentration was higher in active PDB than in inactive PDB patients, whereas there were no differences in OPG, RANKL, sclerostin, VEGF, PGF and ENG plasma levels between active and inactive PDB patients. ALP decreased at 3 and 12 months after zoledronic acid treatment. RANKL levels were reduced and sclerostin levels were increased after 12 months of treatment. PGF levels were lower 12 months after zoledronic acid treatment, whereas there were no differences in plasma VEGF and ENG after zoledronic acid treatment. Summarizing, zoledronic acid treatment is associated to decreases in plasma levels of ALP, RANKL, sclerostin and P1GF in active PDB patients. This treatment may reduce bone turnover and might reduce the pathological vascularisation typical of pagetic bone.

¿Otro tofo gotoso? Las múltiples caras del encondroma / Another gouty tophus? The many faces of the enchondroma

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Polymorphisms in genes implicated in base excision repair (BER) pathway are associated with susceptibility to Paget's disease of bone.

Paget's disease of bone (PDB) is a chronic bone metabolic disorder. Currently, PDB is the second most frequent bone disorder. PDB is a focal disorder affecting the skeleton segmentally but the cause of which is unknown. It has been hypothesised that somatic mutations could be responsible for the mosaicism described in PDB patients. Therefore, our hypothesis is that defective response to DNA damage may lead to somatic mutations favouring an increased risk of PDB. So that we have analysed polymorphisms in DNA repair genes involved in the BER, NER and DSBR pathways in order to evaluate the role of these variants in modulating PDB risk. We found statistically significant differences in genotypic and allelic distribution for polymorphisms in genes implicated in the BER pathway. Our results showed that carrying the allele T of XRCC1 rs1799782 polymorphism and the allele G of APEX rs1130409 polymorphism increased the risk of developing PDB. These polymorphisms could cause a lower DNA repair efficiency and this might lead to local somatic mutations favouring bone metabolic alterations characteristic of PDB. This is the first report showing an association between polymorphism in genes implicated in the BER pathway with PDB.

Shock cardiogénico e isquemia aguda de miembros inferiores como complicaciones de la enfermedad de Kawasaki / Cardiogenic shock and lower limb ischemia as complications of Kawasaki disease

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VAV3 Gene Polymorphism Is Associated with Paget's Disease of Bone.

BACKGROUND AND AIMS: Paget's disease of bone (PDB) is a focal bone disorder affecting the skeleton segmentally. The disease affects osteoclasts which increase in size, number, and activity. One of the etiopathogenic hypotheses is that the disease is genetic. It has been reported that Rho GEF Vav3 is an essential factor in the regulation of osteoclast function, and alteration of the VAV3 gene could influence the development of the disease. The aim of our study was to perform an association study between variants of the VAV3 gene and the risk of developing Paget's disease of bone. PATIENTS AND METHODS: The genotypic and allelic distribution of the VAV3 c.892A>T/p.T298S (rs7528153) polymorphism was compared between a cohort of 238 Spanish subjects with PDB and a cohort of 253 healthy subjects. RESULTS: Our results indicated that individuals carrying the VAV3 rs7528153 TT genotype were at a significantly increased risk of developing PDB (p < 0.001, odds ratio [OR] = 3.15, 95% confidence interval [95% CI] = 1.77-5.61). CONCLUSIONS: These results suggest that inheriting the VAV3 rs7528153 polymorphism is a likely susceptibility factor for developing Paget's disease of bone.

Metalosis como causa de dolor e inflamación en un paciente con prótesis de rodilla: descripción de un caso / Metallosis as a cause of pain and inflammation in a patient with a knee replacement: a case description

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