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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.

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.

Melmed S.,Cedars Sinai Medical Center | Bidlingmaier M.,Medizinische Klinik IV | Mercado M.,Medical Center | Van Der Lely A.J.,Erasmus Medical Center | And 20 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015

Background: A novel oral octreotide formulation was tested for efficacy and safety in a phase III, multicenter, open-label, dose-titration, baseline-controlled study in patients with acromegaly. Methods: We enrolled 155 complete or partially controlled patients (IGF-1 <1.3 × upper limit of normal [ULN], and 2-h integrated GH <2.5 ng/mL) receiving injectable somatostatin receptor ligand (SRL) for ≥3 months. Subjects were switched to 40 mg/d oral octreotide capsules (OOCs), and the dose escalated to 60 and then up to 80 mg/d to control IGF-1. Subsequent fixed doses were maintained for a 7-month core treatment, followed by a voluntary 6-month extension. Results: Of 15 1evaluable subjects initiating OOCs, 65% maintained response and achieved the primary endpoint of IGF-1<1.3×ULN and mean integrated GH <2.5 ng/mL at the end of the core treatment period and 62% at the end of treatment (up to 13 mo). The effect was durable, and 85%of subjects initially controlled on OOCs maintained this response up to 13 months. When controlled on OOCs, GH levels were reduced compared to baseline, and acromegaly-related symptoms improved. Of 102 subjects completing the core treatment, 86% elected to enroll in the 6-month extension. Twenty-six subjects who were considered treatment failures (IGF-1≥1.3×sULN)terminatedearly, and 23 with drew for adverse events, consistent with those known for octreotide or disease related. Conclusions: OOC, an oral therapeutic peptide, achieves efficacy in controlling IGF-1 and GH after switching from injectable SRLs for up to 13 months, with a safety profile consistent with approved SRLs. OOC appears to be effective and safe as an acromegaly monotherapy. Copyright © 2015 by the Endocrine Society.

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.

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.

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