Tsapikouni T.,University of Barcelona |
Tsapikouni T.,CIBER ISCIII |
Garreta E.,University of Barcelona |
Garreta E.,CIBER ISCIII |
And 10 more authors.
Respiratory Physiology and Neurobiology | Year: 2012
High frequency intermittent hypoxia is one of the most relevant injurious stimuli experienced by patients with obstructive sleep apnea (OSA). Given that the conventional setting for culturing cells under intermittent hypoxia conditions is limited by long equilibration times, we designed a simple bioreactor capable of effectively subjecting cultured cells to controlled high-frequency hypoxic/normoxic stimuli. The bioreactor's operation is based on exposing cells to a medium that is bubbled with the appropriate mixture of gases into two separate containers, and from there it is directed to the cell culture dish with the aid of two bidirectional peristaltic pumps. The device was tested on human alveolar epithelial cells (A549) and mouse melanoma cells (B16-F10), subjecting them to patterns of intermittent hypoxia (20s at 5% O2 and 50s at 20% O2), which realistically mimic OSA of up to severe intensity as defined by the apnea hypopnea index. The proposed bioreactor can be easily and inexpensively assembled and is of practical use for investigating the effects of high-rate changes in oxygen concentration in the cell culture medium. © 2012 Elsevier B.V.
De Hollanda A.,Hospital Clinic Universitari |
Casals G.,Hospital Clinic Universitari |
Delgado S.,Hospital Clinic Universitari |
Delgado S.,Institute DInvestigacions Biomediques August Pi Sunyer |
And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015
Context: Factors underlying variable weight loss (WL) after Roux-en-Y gastric bypass (RYGB) are poorly understood. Objective: Our objective was to gain insight on the role of gastrointestinal hormones on poor WL maintenance (P-WLM) following RYGB. Design and Patients: First, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin responses to a standardized mixed liquid meal (SMLM) were compared between subjects with good WL (G-WL, n = 32) or P-WLM (n = 22). Second, we evaluated food intake (FI) following blockade of gut hormonal secretion in G-WL (n = 23) or P-WLM (n = 19) subjects. Finally, the impact of dietary-induced WL on the hormonal response in subjects with P-WLM (n = 14) was assessed. Setting: This study was undertaken in a tertiary hospital. MainOutcomeMeasures: In studies 1and3, the outcomes measures were the areas under the curve of gut hormones following a SMLM; in study 2, FI following subcutaneous injection of saline or octreotide were evaluated. Results: P-WLM associated a blunted GLP-1 (P = .044) and PYY (P = .001) responses and lesser suppression of ghrelin (P=.032) following the SMLM challenge. On saline day, FI in the G-WL (393 ±143 kcal) group was less than in the P-WLM (519±143 Kcal; P=.014) group. Octreotide injection resulted in enlarged FI in both groups (G-WL: 579 ± 248 kcal, P = .014; P-WLM: 798 ± 284 Kcal, P = .036), but the difference in FI between groups remained (P<.001). In subjects with P-WLM, dietary-induced WL resulted in larger ghrelin suppression (P = .046), but no change in the GLP-1 or PYY responses. Conclusion: Our data show gastrointestinal hormones play a role in the control of FI following RYGB, but do not support that changes in GLP-1, PYY, or ghrelin play a major role as determinants of P-WLM after this type of surgery. Copyright © 2015 by the Endocrine Society.
Bosi E.,San Raffaele Scientific Institute |
Bosi E.,Vita-Salute San Raffaele University |
Scavini M.,San Raffaele Scientific Institute |
Scavini M.,Vita-Salute San Raffaele University |
And 6 more authors.
Diabetes Care | Year: 2013
OBJECTIVE We aimed to evaluate the added value of intensive self-monitoring of blood glucose (SMBG), structured in timing and frequency, in noninsulin-treated patients with type 2 diabetes. RESEARCH DESIGN AND METHODSdThe 12-month, randomized, clinical trial enrolled 1,024 patients with noninsulin-treated type 2 diabetes (median baseline HbA1c, 7.3% [IQR, 6.9-7.8%]) at 39 diabetes clinics in Italy. After standardized education, 501 patients were randomized to intensive structured monitoring (ISM) with 4-point glycemic profiles (fasting, preprandial, 2-h postprandial, and postabsorptive measurements) performed 3 days/week; 523 patients were randomized to active control (AC) with 4-point glycemic profiles performed at baseline and at 6 and 12 months. Two primary end points were tested in hierarchical order: HbA1c change at 12 months and percentage of patients at risk target for low and high blood glucose index. RESULTSdIntent-to-treat analysis showed greater HbA1c reductions over 12 months in ISM (20.39%) than in AC patients (20.27%), with a between-group difference of 20.12% (95% CI, 20.210 to 20.024; P = 0.013). In the per-protocol analysis, the between-group difference was 20.21% (20.331 to 20.089; P = 0.0007). More ISM than AC patients achieved clinically meaningful reductions in HbA1c (>0.3, >0.4, or >0.5%) at study end (P< 0.025). The proportion of patients reaching/maintaining the risk target at month 12 was similar in ISM (74.6%) and AC (70.1%) patients (P = 0.131). At visits 2, 3, and 4, diabetes medications were changed more often in ISM than in AC patients (P <0.001). CONCLUSIONSdUse of structured SMBG improves glycemic control and provides guidance in prescribing diabetes medications in patients with relatively well-controlled noninsulintreated type 2 diabetes. © 2013 by the American Diabetes Association.
Solana E.,Autonomous University of Barcelona |
Sahuquillo J.,Autonomous University of Barcelona |
Junque C.,University of Barcelona |
Junque C.,Institute DInvestigacions Biomediques August Pi Sunyer |
And 2 more authors.
Archives of Clinical Neuropsychology | Year: 2012
Although idiopathic normal pressure hydrocephalus (iNPH) is considered a treatable dementia, there is still some controversy regarding the cognitive improvement in these patients. The main aims of this study were to analyze baseline cognitive status and to study the neuropsychological changes after surgical treatment in a sample of 185 consecutive iNPH patients. An additional aim was to identify the variables that influenced the cognitive outcome. Specific tests assessing memory, attention, visual scanning, executive functions (EFs), and motor speed were used before and 6 months after shunting. The cognitive domains most affected at baseline were memory, EFs, attention, and psychomotor speed. After shunting, significant differences in the group as a whole were found in all tests except Digits Forward and Trail Making Part B. However, less than 50% of patients showed a significant improvement when analyzed individually. Previous global cognitive status assessed by Mini-Mental State Examination baseline scores was the best predictor for the cognitive outcome. © The Author 2012.
Ejaz A.,Harvard University |
Martinez-Guino L.,Hospital Sant Joan Of Deu |
Goldfine A.B.,Harvard University |
Ribas-Aulinas F.,University of Barcelona |
And 15 more authors.
Diabetes | Year: 2016
Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin-resistant humans and correlate closely with insulin sensitivity. Moreover, betaine administration to mice with diet-induced obesity prevents the development of impaired glucose homeostasis, reduces hepatic lipid accumulation, increases white adipose oxidative capacity, and enhances whole-body energy expenditure. In parallel with these beneficial metabolic effects, betaine supplementation robustly increased hepatic and circulating fibroblast growth factor (Fgf)21 levels. Betaine administration failed to improve glucose homeostasis and liver fat content in Fgf21-/-mice, demonstrating that Fgf21 is necessary for betaine's beneficial effects. Together, these data indicate that dietary betaine increases Fgf21 levels to improve metabolic health in mice and suggest that betaine supplementation merits further investigation as a supplement for treatment or prevention of type 2 diabetes in humans. © 2016 by the American Diabetes Association.
Benito B.,University of Barcelona |
Benito B.,Institute dInvestigacions Biomediques August Pi Sunyer |
Benito B.,Montreal Heart Institute |
Gay-Jordi G.,Institute dInvestigacions Biomediques August Pi Sunyer |
And 12 more authors.
Circulation | Year: 2011
Background-: Recent clinical studies suggest that endurance sports may promote cardiac arrhythmias. The aim of this study was to use an animal model to evaluate whether sustained intensive exercise training induces potentially adverse myocardial remodeling and thus creates a potential substrate for arrhythmias. Methods and results-: Male Wistar rats were conditioned to run vigorously for 4, 8, and 16 weeks; time-matched sedentary rats served as controls. Serial echocardiograms and in vivo electrophysiological studies at 16 weeks were obtained in both groups. After euthanasia, ventricular collagen deposition was quantified by histological and biochemical studies, and messenger RNA and protein expression of transforming growth factor-21, fibronectin-1, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, procollagen-I, and procollagen-III was evaluated in all 4 cardiac chambers. At 16 weeks, exercise rats developed eccentric hypertrophy and diastolic dysfunction, together with atrial dilation. In addition, collagen deposition in the right ventricle and messenger RNA and protein expression of fibrosis markers in both atria and right ventricle were significantly greater in exercise than in sedentary rats at 16 weeks. Ventricular tachycardia could be induced in 5 of 12 exercise rats (42%) and only 1 of 16 sedentary rats (6%; P≤0.05). The fibrotic changes caused by 16 weeks of intensive exercise were reversed after an 8-week exercise cessation. Conclusions-: In this animal model, we documented cardiac fibrosis after long-term intensive exercise training, together with changes in ventricular function and increased arrhythmia inducibility. If our findings are confirmed in humans, the results would support the notion that long-term vigorous endurance exercise training may in some cases promote adverse remodeling and produce a substrate for cardiac arrhythmias. Copyright © 2011 American Heart Association. All rights reserved.
Fernandez J.,University of Barcelona |
Fernandez J.,Institute dInvestigacions Biomediques August Pi Sunyer |
Fernandez J.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas |
Acevedo J.,University of Barcelona |
And 39 more authors.
Hepatology | Year: 2012
Epidemiology, risk factors, and clinical effect of infections by multiresistant bacteria in cirrhosis are poorly known. This work was a prospective evaluation in two series of cirrhotic patients admitted with infection or developing infection during hospitalization. The first series was studied between 2005 and 2007 (507 bacterial infections in 223 patients) and the second between 2010 and 2011 (162 bacterial infections in 110 patients). In the first series, 32% of infections were community acquired (CA), 32% healthcare associated (HCA), and 36% nosocomial. Multiresistant bacteria (92 infections; 18%) were isolated in 4%, 14%, and 35% of these infections, respectively (P < 0.001). Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E; n = 43) was the main multiresistant organism identified, followed by Pseudomonas aeruginosa (n = 17), methicillin-resistant Staphylococcus aureus (n = 14), and Enterococcus faecium (n = 14). The efficacy of currently recommended empirical antibiotic therapy was very low in nosocomial infections (40%), compared to HCA and CA episodes (73% and 83%, respectively; P < 0.0001), particularly in spontaneous bacterial peritonitis, urinary tract infection, and pneumonia (26%, 29%, and 44%, respectively). Septic shock (26% versus 10%; P < 0.0001) and mortality rate (25% versus 12%; P = 0.001) were significantly higher in infections caused by multiresistant strains. Nosocomial origin of infection (hazard ratio [HR], 4.43), long-term norfloxacin prophylaxis (HR, 2.69), recent infection by multiresistant bacteria (HR, 2.45), and recent use of β-lactams (HR, 2.39) were independently associated with the development of multiresistant infections. Results in the second series were similar to those observed in the first series. Conclusions: Multiresistant bacteria, especially ESBL-producing Enterobacteriaceae, are frequently isolated in nosocomial and, to a lesser extent, HCA infections in cirrhosis, rendering third-generation cephalosporins clinically ineffective. New antibiotic strategies tailored according to the local epidemiological patterns are needed for the empirical treatment of nosocomial infections in cirrhosis. © 2011 American Association for the Study of Liver Diseases.
Guevara M.,Liver Unit Hospital Clinic |
Guevara M.,Institute dInvestigacions Biomediques August Pi Sunyer
Hepatology | Year: 2012
Aims: In patients with cirrhosis and refractory ascites the role of beta-blockers in the development of paracentesis- induced circulatory dysfunction (PICD) is unknown. The aim of this study was to investigate the incidence of PICD before and after discontinuation of beta- blockers in patients with cirrhosis and refractory ascites. A self control cross-over study was performed. Methods: Patients with cirrhosis and refractory ascites treated with beta-blockers were selected. Heart rate, arterial pressure, and plasma renin concentrations (PRC) were collected before, immediately after and 1 week after largevolume paracentesis associated with intravenous albumin administration. Beta-blocker therapy was progressively discontinued after complete endoscopic eradication of varices. The clinical and biological evaluation was then repeated. The presence of PICD was defined as an increase in PRC of at least 50% above baseline 1 week after paracentesis. Results: Ten patients were included (nine men, mean age 59.1 6 10.7 years old). The MELD score was 17.7 6 4.4 and eight patients were Child Pugh C. When patients were given betablockers,the heart rate did not change immediately after paracentesis while mean arterial pressure significantly decreased; PICD developed in eight patients. After beta-blockers were discontinued, the heart rate significantly increased immediately after paracentesis and mean arterial pressure significantly decreased; PICD only developed in one patient; the difference in the incidence of PICD was significant when these same patients were treated with beta-blockers. Conclusions: The use of beta-blockers may be associated with a high risk of PICD in patients with cirrhosis and refractory ascites. © 2012.
Raz I.,Hadassah Hospital |
Ceriello A.,Institute dInvestigacions Biomediques August Pi Sunyer |
Wilson P.W.,Emory University |
Battioui C.,Eli Lilly and Company |
And 5 more authors.
Diabetes Care | Year: 2011
OBJECTIVE - To identify the Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (HEART2D) trial subgroups with treatment difference. RESEARCH DESIGN AND METHODS - In 1,115 type 2 diabetic patients who had suffered from an acute myocardial infarction (AMI), the HEART2D trial compared two insulin strategies targeting postprandial or fasting/premeal glycemia on time until first cardiovascular event (cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or hospitalization for acute coronary syndrome). The HEART2D trial ended prematurely for futility.We used the classification and regression tree (CART) to identify baseline subgroups with potential treatment differences. RESULTS - CART estimated the age of >65.7 years to best predict the difference in time to first event. In the subgroup aged >65.7 years (prandial, n = 189; basal, n = 210), prandial patients had a significantly longer time to first event and a lower proportion experienced a first event (n = 56 [29.6%] vs. n = 85 [40.5%]; hazard ratio 0.69 [95% CI 0.49-0.96]; P = 0.029), despite similar A1C levels. CONCLUSIONS - Older type 2 diabetic AMI survivors may have a lower risk for a subsequent cardiovascular event with insulin targeting postprandial versus fasting/premeal glycemia. © 2011 by the American Diabetes Association.
PubMed | University of Barcelona, Hospital Sant Joan Of Deu, University of Massachusetts Medical School, Institute dInvestigacions Biomediques August Pi Sunyer and 4 more.
Type: Journal Article | Journal: Diabetes | Year: 2016
Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin-resistant humans and correlate closely with insulin sensitivity. Moreover, betaine administration to mice with diet-induced obesity prevents the development of impaired glucose homeostasis, reduces hepatic lipid accumulation, increases white adipose oxidative capacity, and enhances whole-body energy expenditure. In parallel with these beneficial metabolic effects, betaine supplementation robustly increased hepatic and circulating fibroblast growth factor (Fgf)21 levels. Betaine administration failed to improve glucose homeostasis and liver fat content in Fgf21(-/-) mice, demonstrating that Fgf21 is necessary for betaines beneficial effects. Together, these data indicate that dietary betaine increases Fgf21 levels to improve metabolic health in mice and suggest that betaine supplementation merits further investigation as a supplement for treatment or prevention of type 2 diabetes in humans.