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Garcia-Pascual L.,Hospital Universitari Mutua Of Terrassa | Barahona M.J.,Hospital Universitari Mutua Of Terrassa | Perea V.,Hospital Universitari Mutua Of Terrassa | Simo R.,Institute Of Recerca Hospital Universitari Vall Dhebron | Simo R.,Autonomous University of Barcelona
Journal of Clinical Endocrinology and Metabolism | Year: 2017

Context: Hypercalciuria is an adverse event of postsurgical hypoparathyroidism treatment that can lead to renal complications. The collection of 24-hour urine to detect hypercalciuria is often considered unreliable. Objective: The purpose of this study was to find useful predictive biomarkers of hypercalciuria in patients with permanent postsurgical hypoparathyroidism receiving treatment with oral calcium and calcitriol supplements. Design and Setting: The investigation was designed as a prospective cross-sectional study. An outpatient hospital clinic served as the study setting. Patients: Fifty-four consecutive observations were made of 34 stable outpatients with postsurgical hypoparathyroidism taking oral calcium and calcitriol supplements, and 17 adult controls without hypoparathyroidism. Intervention: There were no interventions. Main Outcome Measure: Hypercalciuria was defined as 24-hour urine calcium >300 mg. Results: Patients without hypercalciuria (n = 21) vs those with hypercalciuria (n = 33) had lower levels of serum 1,25-dihydroxyvitamin D (33.5 ± 11.9 pg/mL vs 45.8 ± 9.5 pg/mL; P < 0.001), similar albumincorrected serum calcium (8.3 ± 0.5 vs 8.6 ± 0.5 mg/dL; P = nonsignificant), and serum parathyroid hormone (12.5 ± 5.7 vs 10.7 ± 6.8 pg/mL; P = nonsignificant).Multiple linear regression analysis showed an independent relationship between 1,25-dihydroxyvitamin D and urinary calcium excretion (B = 6.26 1.423; P<0.001). A cutoff value of 33.5 pg/mL for serum 1,25-dihydroxyvitamin D to predict the absence of hypercalciuria had 100% sensitivity and 63.6% specificity, and the area under the receiver operating characteristic curve was 0.797. No patients with serum 1,25-dihydroxyvitamin D levels of <33.5 pg/mL presented with hypercalciuria, regardless of the level of albumin-corrected serum calcium. Conclusions: Routine measurement of serum 1,25-dihydroxyvitamin D may be useful as a biomarker to predict the absence of hypercalciuria in patients with permanent postsurgical hypoparathyroidism who are receiving treatment with oral calcium and calcitriol supplements. © 2017 by the Endocrine Society.


Simo R.,Carlos III Health Institute | Simo R.,Institute Of Recerca Hospital Universitari Vall Dhebron | Guerci B.,Nancy University Hospital Center | Schernthaner G.,Rudolfstiftung Hospital Vienna | And 6 more authors.
Cardiovascular Diabetology | Year: 2015

Objective: The risk of cardiovascular morbidity and mortality is significantly increased in patients with diabetes; thus, it is important to determine whether glucose-lowering therapy affects this risk over time. Changes in cardiovascular risk markers were examined in patients with type 2 diabetes treated with exenatide twice daily (a glucagon-like peptide-1 receptor agonist) or glimepiride (a sulfonylurea) added to metformin in the EURopean EXenAtide (EUREXA) study. Research design and methods: Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n=515) or glimepiride (n=514) until treatment failure defined by hemoglobin A1C. Anthropomorphic measures, blood pressure (BP), heart rate, lipids, and high-sensitivity C-reactive protein (hsCRP) over time were evaluated. Results: Over 36months, twice-daily exenatide was associated with improved body weight (-3.9kg), waist circumference (-3.6cm), systolic/diastolic BP (-2.5/-2.6mmHg), high-density lipoprotein (HDL)-cholesterol (0.05mmol/L), triglycerides (-0.2mmol/L), and hsCRP (-1.7mg/L). Heart rate did not increase (-0.3 beats/minute), and low-density lipoprotein-cholesterol (0.2mmol/L) and total cholesterol (0.1mmol/L) increased slightly. Between-group differences were significantly in favor of exenatide for body weight (P<0.0001), waist circumference (P<0.001), systolic BP (P<0.001), diastolic BP (P=0.023), HDL-cholesterol (P=0.001), and hsCRP (P=0.004). Fewer patients randomized to exenatide twice daily versus glimepiride required the addition of at least one antihypertensive (20.4 vs 26.4%; P=0.026) or lipid-lowering medication (8.4 vs 12.8%; P=0.025). Conclusions: Add-on exenatide twice daily was associated with significant, sustained improvement in several cardiovascular risk markers in patients with type 2 diabetes versus glimepiride. Clinical trial registration: NCT00359762, http://www.ClinicalTrials.gov © 2015 Simó et al.


Barba I.,Hospital Universitari Vall dHebron | Barba I.,Institute Salud Carlos III | Garcia-Ramirez M.,CIBER ISCIII | Garcia-Ramirez M.,Institute Of Recerca Hospital Universitari Vall Dhebron | And 10 more authors.
Investigative Ophthalmology and Visual Science | Year: 2010

PURPOSE. To explore the metabolic profile of vitreous fluid of patients with proliferative diabetic retinopathy (PDR) using 1H-NMR-based metabonomic analysis. METHODS. 1H-NMR spectra were acquired from vitreous samples obtained during vitrectomy from 22 patients with type 1 diabetes with PDR and from 22 nondiabetic patients with macular hole (control group). Data analysis included a principal component analysis and partial least squares discriminant analysis (PLS-DA). In addition, 1H-1H and 1H-13C HMQC correlation spectra were acquired for the identification of metabolites. Furthermore, the main metabolites accounting for the differences in metabolic profile were assessed by current biochemical methods. RESULTS. Lactate was the most abundant metabolite, and it was present at higher levels in samples from PDR patients than from nondiabetic patients (P = 0.02). Glucose was significantly higher in samples from PDR patients than nondiabetic patients (P = 0.03). After removing the lactate peak at 1.35 ppm and with the use of PLS-DA, a model was obtained that was able to correctly classify 19 of 22 patients with PDR and 18 of 22 controls, resulting in a sensitivity of 86% and a specificity of 81%. The main metabolites involved in this specific pattern recognition were galactitol and ascorbic acid (AA); levels of both were significantly lower in PDR patients. CONCLUSIONS. 1H-NMR-based metabonomic analysis of vitreous fluid permits the obtainment of a metabolic signature of PDR. Apart from the higher abundance of lactate and glucose, significant deficits of galactitol and AA are the main metabolic fingerprints of vitreous fluid from PDR patients. © Association for Research in Vision and Ophthalmology.


Moreno R.,Lhospitalet Of Llobregat | Martinez-Gonzalez I.,Lhospitalet Of Llobregat | Rosal M.,Institute Of Recerca Hospital Universitari Vall Dhebron | Nadal M.,Lhospitalet Of Llobregat | And 3 more authors.
Stem Cells and Development | Year: 2012

Prenatal transplantation of genetically engineered mesenchymal stem cells (MSCs) might benefit prevention or treatment of early-onset genetic disorders due to the cells' intrinsic regenerative potential plus the acquired advantage from therapeutic transgene expression. However, a thorough assessment of the safety, accessibility, and behavior of these MSCs in the fetal environment using appropriate animal models is required before we can advance toward a clinical application. We have recently shown that fetal rabbit liver MSCs (fl-MSCs) have superior growth rate, clonogenic capability, and in vitro adherence and differentiation abilities compared with adult rabbit bone marrow MSCs. In this follow-up study, we report safe and widespread distribution of recombinant pSF-EGFP retrovirus-transduced fl-MSCs (EGFP +-fl-MSCs) in neonatal rabbit tissues at 10 days after fetal allogeneic transplantation through both intrahepatic and intra-amniotic administration. Conversely, a more restricted biodistribution pattern according to the route of administration was apparent in the young rabbits intervened at 16 weeks after fetal EGFP +-fl-MSC transplantation. Furthermore, the presence of these cells in the recipients' tissues, tracked with the reporter provirus, was inversely related to the developmental stage of the fetuses at the time of intervention. Long-term engraftment was confirmed both by fluorescence in situ hybridization analysis on touch tissue imprints using a chromosome Y-specific BAC probe, and by immunohistochemical localization of EGFP expression. Finally, there was no evidence of immune responses against the transplanted EGFP +-fl-MSCs or the EGFP transgenic product in the treated young rabbits. Thus, cell transplantation approaches using genetically engineered fetal MSCs may prove particularly valuable to frontier medical treatments for congenital birth defects in perinatology. © Copyright 2012, Mary Ann Liebert, Inc.


Moreno R.,Hospital Duran i Reynals | Martinez-Gonzalez I.,Hospital Duran i Reynals | Rosal M.,Institute Of Recerca Hospital Universitari Vall Dhebron | Farwati A.,Hospital Duran i Reynals | And 2 more authors.
Stem Cells and Development | Year: 2010

Physiological attributes of mesenchymal stem cells (MSCs) including straightforward manipulation, multilineage differentiation, immunoregulation, and tropism for injury settings render them ideal therapeutic agents for tissue repair/regeneration. Nevertheless, further studies in suitable animal models of disease are needed to translate the potential of MSCs into clinical applications. We report here the isolation and preliminary characterization of MSCs from fetal rabbit liver (fl-MSCs). Compared with MSCs isolated from adult rabbit bone marrow, fl-MSCs had superior growth rate, clonogenic capability, and plastic adherence owing to their developmental immaturity. Both cytochemical staining and mRNA expression analysis of fl-MSCs confirmed mesodermal lineage differentiation into adipocytes, osteocytes, and chondrocytes. Moreover, fl-MSCs were capable to prevent lymphocyte proliferation both in a 2-way MLC and upon phytohemagglutinin (PHA) stimulation. In contrast, fl-MSCs co-cultured with allogeneic lymphocytes induced proliferation of the latter. Relatedly, although freshly isolated fl-MSCs did express neither major histocompatibility complex (MHC) class I/II nor CD80/CD86, all these immune synapse components were induced upon in vitro culture. Furthermore, fl-MSCs became efficiently transduced for long-term transgene expression with a retroviral vector. Thus, the special biological qualities of fl-MSCs endow them as model candidate vehicles/agents for gene/cell therapy strategies applied to a variety of rabbit models of injury, such as osteochondral lesions. © 2010, Mary Ann Liebert, Inc.


PubMed | Hospital Universitari Arnau Of Vilanova, Institute Of Recerca Hospital Universitari Vall Dhebron and University of Barcelona
Type: Journal Article | Journal: Obesity (Silver Spring, Md.) | Year: 2015

Cortisolemia and 11HSD1 in liver and adipose tissue are altered in obesity. However, their participation in the development of obesity remains unclear. This study analyzed these parameters in the transition from morbid to type 1 obesity after bariatric surgery.A group of 34 patients with morbid obesity and 22 nonobese subjects were recruited. Initial hypothalamus-pituitary-adrenal (HPA) basal activity and 11HSD1 mRNA expression in liver, subcutaneous (SAT), and visceral adipose tissue (VAT) were evaluated. A year after bariatric surgery (weight loss of 48 kg), these parameters were reappraised in plasma, SAT, and liver.Body weight loss was accompanied by a downshift in basal HPA activity and 11HSD1 expression in SAT. In patients with morbid obesity, 11HSD1 expression correlated positively with BMI in VAT and negatively in liver at 6 and 12 months after surgery. In SAT, a correlation was observed with body weight only when patients showed type 1 obesity. Insulin, glucose, and HOMA correlated positively with all the HPA indicators and 11HSD1 expression in SAT.Body weight loss after bariatric surgery is accompanied by a downshift in basal HPA activity. Hepatic and VAT 11HSD1 expressions in morbid obesity are predictors of body weight loss.

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