PubMed | National Institute of Endocrinology, Institute of Oncology and Radiobiology, International Agency for Research on Cancer IARC, MINES ParisTech and 2 more.
Type: | Journal: BMC genetics | Year: 2015
The incidence of differentiated thyroid carcinoma (DTC) in Cuba is low and the contribution of host genetic factors to DTC in this population has not been investigated so far. Our goal was to assess the role of known risk polymorphisms in DTC cases living in Havana. We genotyped five polymorphisms located at the DTC susceptibility loci on chromosome 14q13.3 near NK2 homeobox 1 (NKX2-1), on chromosome 9q22.33 near Forkhead factor E1 (FOXE1) and within the DNA repair gene Ataxia-Telangiectasia Mutated (ATM) in 203 cases and 212 age- and sex- matched controls. Potential interactions between these polymorphisms and other DTC risk factors such as body surface area, body mass index, size, ethnicity, and, for women, the parity were also examined.Significant association with DTC risk was found for rs944289 near NKX2-1 (OR per A allele = 1.6, 95% CI: 1.2-2.1), and three polymorphisms near or within FOXE1, namely rs965513 (OR per A allele = 1.7, 95% CI: 1.2-2.3), rs1867277 in the promoter region of the gene (OR per A allele = 1.5, 95% CI: 1.1-1.9) and the poly-alanine tract expansion polymorphism rs71369530 (OR per Long Allele = 1.8, 95% CI: 1.3-2.5), only the 2 latter remaining significant when correcting for multiple tests. Overall, no association between DTC and the coding SNP D1853N (rs1801516) in ATM (OR per A Allele = 1.1, 95% CI: 0.7-1.7) was seen. Nevertheless women who had 2 or more pregnancies had a 3.5-fold increase in risk of DTC if they carried the A allele (OR 3.5, 95% CI: 3.2-9.8) as compared to 0.8 (OR 0.8, 95% CI: 0.4-1.6) in those who had fewer than 2.We confirmed in the Cuban population the role of the loci previously associated with DTC susceptibility in European and Japanese populations through genome-wide association studies. Our results on ATM and the number of pregnancies raise interesting questions on the mechanisms by which oestrogens, or other hormones, alter the DNA damage response and DNA repair through the regulation of key effector proteins such as ATM. Due to the small size of our study and to multiple tests, all these results warrant further investigation.
PubMed | Mulhouse Hospital, Hospices Civils de Lyon, University of Lyon, National Institute of Endocrinology and 9 more.
Type: Journal Article | Journal: European thyroid journal | Year: 2016
Physical activity has been hypothesized to influence cancer occurrence through several mechanisms. To date, its relation with thyroid cancer risk has been examined in relatively few studies. We pooled 2 case-control studies conducted in Cuba and Eastern France to assess the relationship between self-reported practice of recreational physical activity since childhood and thyroid cancer risk.This pooled study included 1,008 cases of differentiated thyroid cancer (DTC) matched with 1,088 controls (age range 9-35 and 17-60 years in the French and Cuban studies, respectively). Risk factors associated with the practice of recreational physical activity were estimated using OR and 95% CI. Logistic regressions were stratified by age class, country, and gender and were adjusted for ethnic group, level of education, number of pregnancies for women, height, BMI, and smoking status.Overall, the risk of thyroid cancer was slightly reduced among subjects who reported recreational physical activity (OR = 0.8; 95% CI 0.5-1.0). The weekly frequency (i.e. h/week) seems to be more relevant than the duration (years).Long-term recreational physical activity, practiced since childhood, may reduce the DTC risk. However, the mechanisms whereby the DTC risk decreases are not yet entirely clear.
PubMed | Uppsala University, Skåne University Hospital and National Institute of Endocrinology
Type: Journal Article | Journal: Journal of medical virology | Year: 2016
In an earlier study, infection of human pancreatic islets with epidemic strains of echovirus (E4, E16, E30), with proven but differently ability to induce islet autoimmunity, resulted either in a severe damage (i.e., E16 and E30) or proceeded without visible changes in infected islets (i.e., E4). In this study, the ability of these strains to replicate in beta cells and the consequence of such an infection for beta cell lysis and beta cell function was studied in the pancreatic beta cell lines INS-1, MIN6, and NIT-1. The strains of E16 and E30 did replicate in INS1, MIN6, and NIT1 cells and resulted in a pronounced cytopathic effect within 3 days following infection. By contrast, E4 replicated in all examined insulinoma cells with no apparent cell destruction. The insulin release in response to high glucose stimulation was hampered in all infected cells (P < 0.05) when no evidence of cytolysis was present; however, the adverse effect of E16 and E30 on insulin secretion appeared to be higher than that of the E4 strain. The differential effects of echovirus infection on cell lysis, and beta cell function in the rodent insulinoma INS1, MIN6, and NIT 1 cells reflect those previously obtained in primary human islets and support the notion that the insulin-producing beta cells can harbor a non-cytopathic viral infection.
Gori I.,University of Lausanne |
Gori I.,Cancer Research UK |
Rodriguez Y.,University of Lausanne |
Rodriguez Y.,National Institute of Endocrinology |
And 7 more authors.
Fertility and Sterility | Year: 2013
Objective: To compare the expression of the prostaglandin (PG) E 2 transporter multidrug resistance-associated protein 4 (MRP4) in eutopic and ectopic endometrial tissue from endometriosis patients with that of control subjects and to examine whether MRP4 is regulated by the antiinflammatory lipid lipoxin A4 (LXA4) in endometriotic epithelial cells. Design: Molecular analysis in human samples and a cell line. Setting: Two university hospitals and a private clinic. Patient(s): A total of 59 endometriosis patients and 32 age- and body mass index-matched control subjects undergoing laparoscopy or hysterectomy. Intervention(s): Normal, eutopic, and ectopic endometrial biopsies as well as peritoneal fluid were obtained during surgery performed during the proliferative phase of the menstrual cycle. 12Z endometriotic epithelial cells were used for in vitro mechanistic studies. Main Outcome Measure(s): Tissue MRP4 mRNA levels were quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and localization was analyzed with the use of immunohistochemistry. Cellular MRP4 mRNA and protein were quantified by qRT-PCR and Western blot, respectively. PGE2 was measured in peritoneal fluid and cell supernatants using an enzyme immunoassay (EIA). Result(s): MRP4 was expressed in eutopic and ectopic endometrium, where it was overexpressed in peritoneal lesions and localized in the cytoplasm of glandular epithelial cells. LXA 4 attenuated MRP4 mRNA and protein levels in endometriotic epithelial cells in a dose-dependent manner, while not affecting the expression of enzymes involved in PGE2 metabolism. Investigations employing receptor antagonists and small interfering RNA revealed that this occurred through estrogen receptor α. Accordingly, LXA4 treatment inhibited extracellular PGE2 release. Conclusion(s): We report for the first time that MRP4 is expressed in human endometrium, elevated in peritoneal endometriosis, and modulated by LXA4 in endometriotic epithelial cells. © 2013 American Society for Reproductive Medicine, Published by Elsevier Inc.
Arana Rosainz M.D.J.,National Institute of Endocrinology |
Ojeda M.O.,National Institute of Endocrinology |
Acosta J.R.,National Institute of Endocrinology |
Elias-Calles L.C.,National Institute of Endocrinology |
And 7 more authors.
Journal of Sexual Medicine | Year: 2011
Introduction. Erectile dysfunction (ED) is highly prevalent among type 2 diabetes mellitus patients (T2DM). Although a link among systemic inflammation, endothelial dysfunction, and ED is described in clinical situations mainly related with coronary heart disease (CHD) risk, evidences of this link in T2DM patients are rather limited. Aims. To evaluate the association between endothelial dysfunction and balance of pro-/anti-inflammatory mediators with ED presence and severity in T2DM. Methods. We conducted a cross-sectional study of 190 T2DM patients without symptomatic CHD, 150 out of them with ED and 40 without ED. Serum levels of E-selectin, intercellular adhesion molecule-1, tumor necrosis factor-α (TNF-α), and interleukin (IL)-10 were measured using specific enzyme-linked immunosorbent assays (ELISAs). ED presence and severity were tested by the five-item version of the International Index of Erectile Function questionnaire. Main Outcome Measures. Differences in circulating levels of endothelial dysfunction (ICAM-1, E-selectin) and inflammatory/anti-inflammatory (TNF-α, IL-10, TNF-α:IL-10 ratio) markers between T2DM patients with and without ED, and assessment of biomarkers ED predictive value while adjusting for other known ED risk factors. Results. Patients with ED were older and had longer duration of diabetes than patients without ED. E-selectin serum levels were significantly increased, while IL-10 were lower in patients with ED; because TNF-α levels tend to be higher, TNF-α:IL-10 ratio was more elevated in ED patients. No significant differences of ICAM-1 levels were observed between study groups. Endothelial activation markers and TNF-α, as well as diabetes duration, were negatively correlated with erectile function. On multivariate analysis including age, duration of diabetes, insulin treatment, hypertension, insulin resistance, fair-to-poor glycemic control, and metabolic syndrome, increments in E-selectin levels and TNF-α:IL-10 ratio predicted independently ED presence, while IL-10 increases were associated with lower risk of ED in T2DM patients. Conclusions. ED in T2DM patients without symptomatic CHD is associated with systemic endothelial dysfunction and a predominant, imbalanced low-grade inflammatory response. © 2011 International Society for Sexual Medicine.
PubMed | University of Matanzas, University of Habana and National Institute of Endocrinology
Type: Journal Article | Journal: Reproductive sciences (Thousand Oaks, Calif.) | Year: 2016
Several epidemiologic studies in humans have shown a relationship between pregestational obesity and congenital malformations in offsprings. However, there are no experimental evidence in animal models of obesity and pregnancy that reproduce the teratogenesis induced by this pathological condition.To evaluate the effect of monosodium glutamate-induced obesity on embryonic development.Female rats received subcutaneously (4 mg/g body weight) monosodium glutamate (MSG) solution or saline solution 0.9% (vehicle control) at days 2, 4, 6, 8, and 10 of life. At 90 days of age, all animals were mated, and on day 11 of pregnancy, the animals were killed. Biochemical variables (glucose, triglycerides, total cholesterol, and insulin) were determined in plasma of dams and embryo homogenates (DNA and protein content, advanced oxidation protein products). Embryos were evaluated for malformations, crown-rump length, and somite number.Obese rats presented higher triglyceride levels as compared to nonobese rats. Increased proportion of malformed embryos, decreased crown-rump length, somite number, DNA, and protein content were observed in offspring of obese rats.The model of obesity induced with MSG reproduces the maternal obesity-induced teratogenesis. The hypertriglyceridemia observed in MSG obese pregnant rats could be related to increased birth defect.
Montes-Brown J.,Center for Research and Rehabilitation of Hereditary Ataxias |
Sanchez-Cruz G.,Center for Research and Rehabilitation of Hereditary Ataxias |
Garcia A.M.,University of Habana |
Baez M.E.,National Institute of Endocrinology |
Velazquez-Perez L.,Center for Research and Rehabilitation of Hereditary Ataxias
Acta Neurologica Scandinavica | Year: 2010
Objectives - To explore cardiovascular autonomic regulation in Spinocerebellar ataxia type 2 (SCA2) patients, using heart rate variability (HRV) analysis and neurophysiologic autonomic reflex tests, and determine relations and causal related factors of dysautonomia in SCA2. Materials and methods - Heart rate variability indices for 5-min series of RR intervals were analyzed in 97 SCA2 patients, assessed quantitatively for somatic and autonomic nervous system complaints applying the International Cooperative Ataxia Rating Scale and Scales for Outcomes in Parkinson's disease (SCOPA-AUT), respectively. Autonomic testing included: resting control, standing, Valsalva maneuver and deep breathing. Results - Mean RR, long- and short-term variability indices and spectral density power (LF, HF) indices were lower in the patients group, whereas LF/HF ratio and LF (nu) were higher. Highly differences between groups were observed for seven diagnostic autonomic test indices. Significant correlations were found between different clinical and demographic indices and between clinical indices and some HRV indices. Conclusions - We confirm the presence of cardiovascular autonomic dysfunction in a large group of SCA2 patients. ©2010 The Authors Journal compilation © 2010 Blackwell Munksgaard.
Cabrera-Rego J.O.,Hospital Manuel Fajardo |
Iacobellis G.,University of Miami |
Castillo-Herrera J.A.,Hospital Manuel Fajardo |
Valiente-Mustelier J.,National Institute of Cardiology and Cardiovascular Surgery |
And 3 more authors.
Pediatric Cardiology | Year: 2014
To determine the association between epicardial fat thickness and carotid arterial stiffness, carotid intima-media thickness (CMIT), left atrial (LA) volume, and left-ventricular (LV) geometry parameters in obese children and adolescents compared with controls. A case-control study was performed in 96 children and adolescents (obese n = 66, controls n = 30) age 9-16 years old (38 female and 58 male, mean age 11.7 ± 2.8 years) undergoing transthoracic echocardiography and carotid artery ultrasound. Clinical, anthropometric, and biochemical determinations were also recorded. Epicardial fat thickness (2.76 ± 1.2 vs. 1.36 ± 0.7 mm, p < 0.001), LA volume (35.7 ± 13.2 vs. 28.9 ± 9.8 mL, p = 0.008), LV mass (118.3 ± 38.6 vs. 96.4 ± 35.4 mL, p = 0.008), CIMT (0.48 ± 0.07 vs. 0.44 ± 0.05 mm, p = 0.019), and local pulse wave velocity (LPWV; 3.7 ± 0.5 vs. 3.2 ± 0.4 m/seg, p = 0.007) were significantly increased in obese children and adolescents compared with controls. Epicardial fat showed a significant and positive correlation with LA volume, LV mass, and LPWV as well as a significant and independent association with increased CIMT (odds ratio (OR) = 3.19 [1.88-7.99], p = 0.005) in the study population. Epicardial fat thickness is linked to obesity, carotid subclinical atherosclerosis, and cardiac geometry parameters and might be a useful tool for the cardiovascular risk stratification in children and adolescents. © 2013 Springer Science+Business Media New York.
Janjgava S.,Tbilisi State University |
Zerekidze T.,Tbilisi State University |
Uchava L.,Tbilisi State University |
Giorgadze E.,Tbilisi State University |
Asatiani K.,National Institute of Endocrinology
European journal of medical research | Year: 2014
BACKGROUND: Multiple epidemiological studies have shown that low testosterone levels are associated with and predict the future development of type 2 diabetes mellitus and the metabolic syndrome. The aim of our study was to show the influence of testosterone replacement therapy on obesity, HbA1c level, hypertension and dyslipidemia in patients with diabetes mellitus and androgen deficiency.METHODS: One hundred and twenty-five male patients with diabetes mellitus were screened; 85 subjects aged 41 to 65 years, with BMI from 27.0 to 48.0 kg/m(2), were randomized in a placebo-controlled study. They also underwent a routine physical examination and selected by free testosterone examination. We divided patients into two groups: 1) treatment group, where we used diet, physical activity, patient's antidiabetic therapy and testosterone replacement therapy; 2) placebo group, where we used diet, physical activity, patient's antidiabetic therapy and placebo.RESULTS: After 6 months of treatment we repeated the diagnostic assessments: lipid profile was improved in both groups but in first group it was clinically significant. Free testosterone level increased in all groups, but in group I was clinically significant. HbA1c decreased in both groups, but in group I we obtained the best result. Leptin level after treatment was approximately the same in both groups. Also, blood pressure was reduced in both groups but results were similar.CONCLUSIONS: Our study demonstrated that it is possible to break this metabolic vicious circle by raising testosterone levels in diabetic men with androgen deficiency. Re-instituting physiological levels of testosterone, as the study has shown, has an important role in reducing the prevalence of diabetic complications.