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1.
Rev Esp Salud Publica ; 942020 Jan 16.
Artigo em Espanhol | MEDLINE | ID: mdl-31942868

RESUMO

OBJECTIVE: There are few epidemiological studies on acute poisonings from pesticides, industrials and household products in Spain. The objective of this work is to describe the epidemiological and clinical profile of acute poisonings by chemical products in our country, and analyze their annual evolution. METHODS: The Spanish Toxicovigilance System (SETv) is a prospective registry that includes 32 Emergency Departments and Intensive Care Units in Spain. An observational descriptive study of acute poisoning by chemical agents (excluding pharmacological products and illicit drugs) was carried out, within 1999-2014. Statistical analysis was performed using Chi-square or exact Fisher's tests. Non-parametric continuous variables were compared using the Mann-Whitney U test. P-value less than 0.05 were considered significant. RESULTS: The 10,548 cases studied had a mean age of 38.41 (±22.07) years, being significantly higher in women (p=0.0001). 67.7% of the poisonings occurred at home, and the most frequent routes of exposure were respiratory (48.3%), digestive (35.3%) and ocular (13.1%). The most frequent toxic groups were toxic gases (31%), caustics (25.6%) and irritant gases (12.1%). Of the patients that required treatment (76.2%), antidotes were used in 27.2%. 20.6% of the patients were admitted at Hospital, with a median stay of 32 (±151.94) days, with significant differences for pesticides and solvents (p=0.02). Sequelae were presented at discharge in 2.1% of patients. Mortality was 1.4% (146 patients) with a mean age of 62.08 years (±19.58) (p=0.0001). CONCLUSIONS: The reduction of chemical poisonings should be prevented in the domestic environment, taking into account the sources of exposure to carbon monoxide and the handling of household cleaning products, both caustic liquids and the generation of irritating gases when mixed.

2.
Int J Epidemiol ; 48(6): 1839-1849, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31329884

RESUMO

BACKGROUND: The association of low-level exposure to metals and metal mixtures with cardiovascular incidence in the general population has rarely been studied. We flexibly evaluated the association of urinary metals and metal mixtures concentrations with cardiovascular diseases in a representative sample of a general population from Spain. METHODS: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured in 1171 adults without clinical cardiovascular diseases, who participated in the Hortega Study. Cox proportional hazard models were used for evaluating the association between single metals and cardiovascular incidence. We used a Probit extension of Bayesian Kernel Machine Regression (BKMR-P) to handle metal mixtures in a survival setting. RESULTS: In single-metal models, the hazard ratios [confidence intervals (CIs)] of cardiovascular incidence, comparing the 80th to the 20th percentiles of metal distributions, were 1.35 (1.06, 1.72) for Cu, 1.43 (1.07, 1.90) for Zn, 1.51 (1.13, 2.03) for Sb, 1.46 (1.13, 1.88) for Cd, 1.64 (1.05, 2.58) for Cr and 1.31 (1.01, 1.71) for V. BKMR-P analysis was confirmatory of these findings, supporting that Cu, Zn, Sb, Cd, Cr and V are related to cardiovascular incidence in the presence of the other metals. Cd and Sb showed the highest posterior inclusion probabilities. CONCLUSIONS: Urine Cu, Zn, Sb, Cd, Cr and V were independently associated with increased cardiovascular risk at levels relevant for the general population of Spain. Urine metals in the mixture were also jointly associated with cardiovascular incidence, with Cd and Sb being the most important components of the mixture.

4.
J Cell Biochem ; 120(8): 13115-13120, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30883882

RESUMO

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.

5.
Int J Vitam Nutr Res ; : 1-5, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30789807

RESUMO

OBJECTIVE: The aim of this study was to evaluate the relationship between vitamin D levels at baseline and after 12 weeks of supplementation/exposure to sunlight and VDR genotypes (BsmI, TaqI and ApaI) and haplotypes in a homogeneous population of postmenopausal women. METHODS: We made a prospective study in which 151 women were randomized to two groups: One with 1000 mg of calcium and 800 IU vitamin D supplementation (102 women) and a placebo group with neither calcium or vitamin D supplementation (49 women). The follow-up was from May to September 2012.Vitamin D was determined by chemiluminescent immunoassay. Genotypes were determined using the Sequenomi Plexplatform and haplotypes using PHASE software. RESULTS: Baseline (25 ± 10 ng/ml vs.23 ± 9 ng/ml, p > 0.05) and 12-week (32 ± 8 ng/ml vs.29 ± 10 ng/ml, p > 0.05) vitamin D levels were similar between the two groups. The genetic study was made in the total population. There were no differences in baseline and final levels of vitamin D in terms of genotypes and haplotypes, except for the Bat haplotype, whose baseline values were lower (25OHD: 21 ± 10 ng/ml vs. 21 ± 10 ng/ml, p = 0.038). The rate of nonresponders in this group was 15 % (p = 0.001), compared with 9 %, 2 % and 3 % in the other groups. CONCLUSIONS: The Bat haplotype was associated with lower baseline levels of vitamin D and a worse response to supplementation and, therefore, may be a risk factor for vitamin D deficiency.

6.
Environ Int ; 123: 171-180, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30529889

RESUMO

INTRODUCTION: Few studies have investigated the role of exposure to metals and metal mixtures on oxidative stress in the general population. OBJECTIVES: We evaluated the cross-sectional association of urinary metal and metal mixtures with urinary oxidative stress biomarkers, including oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8­oxo­7,8­dihydroguanine (8-oxo-dG), in a representative sample of a general population from Spain (Hortega Study). METHODS: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured by ICPMS in 1440 Hortega Study participants. RESULTS: The geometric mean ratios (GMRs) of GSSG/GSH comparing the 80th to the 20th percentiles of metal distributions were 1.15 (95% confidence intervals [95% CI]: 1.03-1.27) for Mo, 1.17 (1.05-1.31) for Ba, 1.23 (1.04-1.46) for Cr and 1.18 (1.00-1.40) for V. For MDA, the corresponding GMRs (95% CI) were 1.13 (1.03-1.24) for Zn and 1.12 (1.02-1.23) for Cd. In 8-oxo-dG models, the corresponding GMR (95% CI) were 1.12 (1.01-1.23) for Zn and 1.09 (0.99-1.20) for Cd. Cr for GSSG/GSH and Zn for MDA and 8-oxo-dG drove most of the observed associations. Principal component (PC) 1 (largely reflecting non-essential metals) was positively associated with GSSG/GSH. The association of PC2 (largely reflecting essential metals) was positive for GSSG/GSH but inverse for MDA. CONCLUSIONS: Urine Ba, Cd, Cr, Mo, V and Zn were positively associated with oxidative stress measures at metal exposure levels relevant for the general population. The potential health consequences of environmental, including nutritional, exposure to these metals warrants further investigation.


Assuntos
Poluentes Ambientais/urina , Metais Pesados/urina , Estresse Oxidativo , Adulto , Idoso , Biomarcadores/urina , Estudos Transversais , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Glutationa/urina , Humanos , Masculino , Malondialdeído/urina , Pessoa de Meia-Idade , Espanha
9.
J Nutrigenet Nutrigenomics ; 10(5-6): 139-145, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29151102

RESUMO

AIMS: The objective of this study was to determine whether vitamin D and genistein supplementation had an additive beneficial effect on levels of vitamin D and bone markers and whether this effect was mediated by genes regulating isoflavone metabolism. MATERIALS AND METHODS: We carried out a prospective study in postmenopausal women randomized to calcium and vitamin D supplementation or calcium, vitamin D, and genistein supplementation. Vitamin D, parathyroid hormone (PTH), cross-linked C-telopeptide (CTX), and procollagen 1 N-terminal (P1NP) were determined by electrochemiluminescence. Three SNPs - rs2231142 (ABCG2), rs358231 (cytosolic ß-glucosidase [CBG]), and rs2273697 (ABCC2) - were determined. RESULTS: We included 102 women. The effects on bone remodeling were similar: rises in vitamin D were significantly associated with reductions in PTH, CTX, and P1NP. Pharmacogenomic analysis of the genotypes showed that, in AT heterozygotes of the CBG1368T>A polymorphism, CTX and P1NP were not reduced. CONCLUSION: Genistein added to calcium and vitamin D supplementation had no additional effect. The supplementation of individual AT heterozygotes of the CBG1368T>A polymorphism had no effect on markers of bone remodeling.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Genisteína/administração & dosagem , Isoflavonas/metabolismo , Vitamina D/sangue , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Biomarcadores/sangue , Cálcio na Dieta/administração & dosagem , Colágeno Tipo I/sangue , Suplementos Nutricionais , Feminino , Genisteína/metabolismo , Genótipo , Voluntários Saudáveis , Humanos , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas de Neoplasias/genética , Nutrigenômica , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Polimorfismo de Nucleotídeo Único , Pós-Menopausa , Pró-Colágeno/sangue , Estudos Prospectivos , Estações do Ano , Vitamina D/administração & dosagem , beta-Glucosidase/genética
10.
Surg Obes Relat Dis ; 10(2): 299-303, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24411193

RESUMO

OBJECTIVES: The aim of this experimental study was to evaluate the expression of 4 genes (osteocalcin, sclerostin (SOST), insulin receptor, and transcription factor forkhead box protein (FOXO1) in the bone cells of Goto-Kakizaki (GK) rats and the expression of these genes in response to bariatric surgery. METHODS: We designed an experimental study with 3 arms (Wistar rats, nonoperated GK rats, and GK rats with gastrojejunal bypass). Gene expression (osteocalcin, insulin receptor, FOXO1, SOST) was measured at baseline and after surgery. Plasma levels of glucose, insulin, homeostasis model assessment (HOMA), glucagon-like peptide 1 (GLP-1), and the production of insulin were measured at baseline and at 60 minutes by pancreatic islets. RESULTS: GK rats had decreased levels of expression of osteocalcin (50.86 ± 19.21 versus 16.78 ± 22.11, P = .031), insulin receptor (1.45 ± .44 versus .54 ± .35, P = .020), and SOST (.92 ± .05 versus .43 ± .47, P = .048) compared with Wistar rats. Gene expression in GK rats, operated and nonoperated, was similar. In nonoperated GK rats, there was a negative correlation between the SOST gene and plasma insulin (r:-.786, P = .021) and the production of insulin by pancreatic islets at 60 minutes (r:-0.857, P = .014). GLP-1 increased after surgery. CONCLUSION: Diabetic GK rats presented a reduced expression of the osteocalcin, insulin receptor, and SOST genes. There was an inverse relationship between SOST and plasma and local insulin. We found no changes in the expression of bone genes that regulate energy metabolism after gastrojejunal bypass.


Assuntos
Proteínas Morfogenéticas Ósseas/biossíntese , Osso e Ossos/metabolismo , Metabolismo Energético/fisiologia , Fatores de Transcrição Forkhead/biossíntese , Regulação da Expressão Gênica , Proteínas do Tecido Nervoso/biossíntese , Osteocalcina/biossíntese , Receptor de Insulina/biossíntese , Animais , Cirurgia Bariátrica , Proteínas Morfogenéticas Ósseas/genética , Osso e Ossos/patologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Fatores de Transcrição Forkhead/genética , Marcadores Genéticos/genética , Genótipo , Masculino , Proteínas do Tecido Nervoso/genética , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Osteocalcina/genética , Ratos , Ratos Wistar , Receptor de Insulina/genética
11.
Rheumatol Int ; 34(8): 1073-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24311107

RESUMO

Although their primary therapeutic indications are different, aminobisphosphonates and statins target enzymes in the mevalonate pathway, which is critical for bone homeostasis. Previous studies have shown that some polymorphisms of the gene encoding farnesyl diphosphate synthase (FDPS), the main target of aminobisphosphonates, modulate the response to these drugs. In this study, we explored whether those single nucleotide polymorphisms (SNPs) also influence the changes in bone mineral density (BMD) following therapy with statins. Sixty-six patients with coronary heart disease were studied at baseline and after 1-year therapy with atorvastatin. BMD was measured by DXA. Three SNPs of the FDPS gene (rs2297480, rs11264359 and rs17367421) were analyzed by using Taqman assays. The results showed that there was no association between the SNPs and basal BMD. However, rs2297480 and rs11264359 alleles, which are in linkage disequilibrium, were associated with changes in hip BMD following atorvastatin therapy. Thus, patients with AA genotype at the rs2297480 locus had a 0.8 ± 0.8 % increase in BMD at the femoral neck, whereas in patients with AC/CC genotypes, BMD showed a 2.3 ± 0.8 % decrease (p = 0.02). Similar results were obtained regarding changes of BMD at the femoral trochanter and when alleles at the rs11264359 locus were analyzed. However, there was no association between BMD and rs17367421 alleles. In conclusion, these results suggest that polymorphisms of the FDPS gene may influence the bone response to various drugs targeting the mevalonate pathway, including not only aminobisphosphonates but also statins.


Assuntos
Densidade Óssea/efeitos dos fármacos , Doença das Coronárias/tratamento farmacológico , Fêmur/efeitos dos fármacos , Geraniltranstransferase/genética , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Polimorfismo de Nucleotídeo Único , Pirróis/uso terapêutico , Absorciometria de Fóton , Idoso , Atorvastatina , Doença das Coronárias/diagnóstico , Feminino , Fêmur/diagnóstico por imagem , Fêmur/enzimologia , Frequência do Gene , Genótipo , Geraniltranstransferase/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Farmacogenética , Fenótipo , Fatores de Tempo , Resultado do Tratamento
12.
Obes Surg ; 24(1): 37-41, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23708991

RESUMO

BACKGROUND: The aim of this study was to evaluate gene expression of bone remodeling markers in type 2 diabetic Goto-Kakizaki (GK) nonobese rats after gastrojejunal bypass and sleeve gastroplasty and their relationship with hormonal parameters. METHODS: We designed an experimental study in three groups of GK rats (nonoperated gastrojejunal bypass and sleeve gastroplasty). Gene expression of markers of bone remodeling and levels of insulin, leptin, and glucagon-like peptide-1 (GLP-1) were determined. RESULTS: GK rats had decreased levels of osteocalcin expression compared with Wistar rats. Gene expression of markers of bone remodeling in GK rats was similar in the three groups studied, although there was a trend to decreased receptor activator for nuclear factor κ B ligand (RANKL) in gastroplasty rats. Significant differences in the osteocalcin/RANKL ratio were observed between controls and gastrojejunal bypass rats compared with gastroplasty rats. The behavior of gastrointestinal hormones was antagonistic (GLP-1 gastrojejunal bypass 1.54 ± 0.24 ng/ml vs. GLP-1 gastroplasty 0.673 ± 0.09, p = 0.0001; leptin gastrojejunal bypass 1,178 ± 0.474 pg/ml vs. leptin gastroplasty 7,391 ± 4,054 pg/ml, p = 0.002). There was a reduction in leptin in the bypass group associated with an increase in gastrectomized rats. In gastrectomized rats, there was a trend toward an inverse relationship between leptin and RANKL (r = -0.771, p = 0.072). This relationship was more marked in the totality of operated rats, n = 12 (r = -0.608, p = 0.036). CONCLUSION: Our results show a more favorable profile of sleeve gastroplasty on bone remodeling. There was a trend to an increase in the expression of the osteocalcin gene, which is probably mediated by increased expression of leptin that inhibits the expression of RANKL.


Assuntos
Remodelação Óssea/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/cirurgia , Derivação Gástrica , Gastroplastia , Osteocalcina/genética , Ligante RANK/genética , Animais , Biomarcadores/análise , Modelos Animais de Doenças , Expressão Gênica , Masculino , Osteocalcina/biossíntese , Ligante RANK/biossíntese , Ratos , Ratos Wistar
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