Mora murri pierri - Academia.edu (original) (raw)
Papers by Mora murri pierri
Diabetes Care
OBJECTIVE: Cell death determines the onset of obesity and associated insulin resistance. Here, we... more OBJECTIVE: Cell death determines the onset of obesity and associated insulin resistance. Here, we analyze the relationship among obesity, adipose tissue apoptosis, and insulin signaling. RESEARCH DESIGN AND METHODS: The expression levels of initiator (CASP8/9) and effector (CASP3/7) caspases as well as antiapoptotic B-cell lymphoma (BCL)2 and inflammatory markers were assessed in visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with different degrees of obesity and without insulin resistance or diabetes. Adipose tissue explants from lean subjects were cultured with TNF-a or IL-6, and the expression of apoptotic and insulin signaling components was analyzed and compared with basal expression levels in morbidly obese subjects. RESULTS SAT and VAT exhibited increased CASP3/7 and CASP8/9 expression levels and decreased BCL2 expression with BMI increase. These changes were accompanied by increased inflammatory cytokine mRNA levels and macrophage infiltration markers. In...
Surgery for Obesity and Related Diseases, 2012
Obesity is very often accompanied by other diseases, with the most common type 2 diabetes mellitu... more Obesity is very often accompanied by other diseases, with the most common type 2 diabetes mellitus and cardiovascular complications. Bariatric surgery is the most effective strategy for treating morbidly obese patients. We evaluated the metabolic changes that occur in the early stage after 2 types of bariatric surgery, biliopancreatic diversion of Scopinaro (BPD) and sleeve gastrectomy (SG), in morbidly obese patients. The study was undertaken in 31 nondiabetic morbidly obese patients (7 men and 24 women). Of the 31 patients, 18 underwent BPD and 13 underwent SG. All patients were examined before bariatric surgery (baseline) and at 15, 30, 45, and 90 days postoperatively. Significant improvement occurred in the anthropometric variables after the 2 types of bariatric surgery, without significant differences between the 2 types of interventions. In patients undergoing BPD, the serum glucose, cholesterol, triglycerides, high-density lipoprotein cholesterol, and free fatty acids were significantly reduced. The changes that occurred in these biochemical variables after SG were not significant. Insulin resistance decreased significantly during the 90 days after surgery, with the greatest decrease at 15 days. However, in the patients who underwent SG, insulin resistance worsened at 15 days and later diminished. The results of the present study have shown that the surgical technique that excludes the duodenum (i.e., BPD) has immediate postoperative changes in the degree of insulin resistance in morbidly obese patients compared to those techniques that do not exclude the duodenum (i.e., SG).
Molecular and Cellular Endocrinology, 2013
The mechanisms involved in the progression to overt diabetes in pre-obese subjects remain unclear... more The mechanisms involved in the progression to overt diabetes in pre-obese subjects remain unclear. Therefore, a nontargeted evaluation of differences in the protein abundance of visceral adipose tissue (VAT) obtained from pre-obese diabetic subjects and pre-obese subjects showing normal glucose tolerance may provide novel insights on the molecular processes involved in the progression to overt diabetes in pre-obesity. Diabetic patients showed increased VAT abundance of glutathione S-transferase Mu 2, peroxiredoxin-2, antithrombin-III, apolipoprotein A-IV, Ig j chain C region, mitochondrial aldehyde dehydrogenase and actin, and decreased abundance of annexin-A1, retinaldehyde dehydrogenase-1, and vinculin, compared with their non-diabetic counterparts. These proteins are involved in cytoskeleton function and structure, oxidative stress, inflammation and retinoid metabolism. The presence of diabetes influences the VAT abundance of several proteins. Hence, the proteins identified here could be considered candidate molecules in future studies addressing the role that VAT dysfunction plays in the development of type 2 diabetes.
Journal of Agricultural and Food Chemistry, 2013
Human Reproduction Update, 2013
background: Oxidative stress might be associated with polycystic ovary syndrome (PCOS), but relat... more background: Oxidative stress might be associated with polycystic ovary syndrome (PCOS), but relatively small studies published to date do not permit reaching a definitive conclusion. We aimed at conducting a systematic review and meta-analysis of studies evaluating circulating markers of oxidative stress in patients with PCOS. methods: We conducted a systematic review of studies reporting circulating markers of oxidative stress in women with PCOS and controls published up to June 2012, using Entrez PubMed and EMBASE online facilities. Meta-analysis calculated standardized mean differences (SMDs) and 95% confidence intervals (95CI). results: From 1633 potential studies identified electronically, 68 studies, including 4933 PCOS patients and 3671 controls, were selected. For each of nine circulating markers of oxidative stress, an individual meta-analysis was conducted. Compared with control women, patients with PCOS presented higher circulating concentrations of homocysteine (23% increase, SMD 0.6, 95CI, 0.4-0.8), malondialdehyde (47% increase, SMD 1.9, 95CI 1.2-2.6) and asymmetric dimethylarginine (36% increase, SMD 1.1, 95CI 0.6-1.6), and increased superoxide dismutase activity (34% increase, SMD 1.0, 95CI 0.5-1.4) and decreased glutathione levels (50% decrease, SMD 23.7, 95CI 26.2 to 21.2) and paraoxonase-1 activity (32% decrease, SMD 20.9, 95CI 21.3 to 20.4). Similar results were found when restricting the analyses to studies in which patients and controls were matched for age and body mass index. conclusions: Circulating markers of oxidative stress are abnormal in women with PCOS independent of weight excess. This finding suggests that oxidative stress may participate in the pathophysiology of this common disorder.
Diabetes Care, 2013
OBJECTIVEdCell death determines the onset of obesity and associated insulin resistance. Here, we ... more OBJECTIVEdCell death determines the onset of obesity and associated insulin resistance. Here, we analyze the relationship among obesity, adipose tissue apoptosis, and insulin signaling.
Current Pharmaceutical Design, 2013
Chronic low-grade subclinical inflammation has been increasingly recognized as an interposer in t... more Chronic low-grade subclinical inflammation has been increasingly recognized as an interposer in the endocrine, metabolic and reproductive disturbances that characterize the polycystic ovary syndrome (PCOS). Abdominal adiposity and obesity are often present in PCOS. Mounting evidence indicates that adipose tissue is involved in innate and adaptive immune responses. Continuous release of inflammatory mediators such as cytokines, acute phase proteins, and adipokines perpetuates the inflammatory condition associated with obesity in women with PCOS, possibly contributing to insulin resistance and other long-term cardiometabolic risk factors. Genetic variants in the genes encoding inflammation-related mediators underlie the development of PCOS and their interaction with environmental factors may contribute to the heterogeneous clinical phenotype of this syndrome. In the future, strategies ameliorating inflammation may prove useful for the management of PCOS and associated conditions.
Clinical Nutrition Supplements, 2008
The American Journal of Clinical Nutrition, 2012
Background: Few studies have investigated the effect of dietary polyphenols on the complex human ... more Background: Few studies have investigated the effect of dietary polyphenols on the complex human gut microbiota, and they focused mainly on single polyphenol molecules and select bacterial populations. Objective: The objective was to evaluate the effect of a moderate intake of red wine polyphenols on select gut microbial groups implicated in host health benefits. Design: Ten healthy male volunteers underwent a randomized, crossover, controlled intervention study. After a washout period, all of the subjects received red wine, the equivalent amount of dealcoholized red wine, or gin for 20 d each. Total fecal DNA was submitted to polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis and real-time quantitative PCR to monitor and quantify changes in fecal microbiota. Several biochemical markers were measured. Results: The dominant bacterial composition did not remain constant over the different intake periods. Compared with baseline, the daily consumption of red wine polyphenol for 4 wk significantly increased the number of Enterococcus, Prevotella, Bacteroides, Bifidobacterium, Bacteroides uniformis, Eggerthella lenta, and Blautia coccoides-Eubacterium rectale groups (P , 0.05). In parallel, systolic and diastolic blood pressures and triglyceride, total cholesterol, HDL cholesterol, and C-reactive protein concentrations decreased significantly (P , 0.05). Moreover, changes in cholesterol and C-reactive protein concentrations were linked to changes in the bifidobacteria number. Conclusion: This study showed that red wine consumption can significantly modulate the growth of select gut microbiota in humans, which suggests possible prebiotic benefits associated with the inclusion of red wine polyphenols in the diet. This trial was registered at controlled-trials.com as ISRCTN88720134.
AGE, 2013
Aging negatively affects angiogenesis which is found to be linked to declined vascular endothelia... more Aging negatively affects angiogenesis which is found to be linked to declined vascular endothelial growth factor (VEGF) production. Adult human thymus degenerates into fat tissue (thymus adipose tissue (TAT)). Recently, we described that TAT from cardiomyopathy ischemic subjects has angiogenic properties. The goal of our study was to analyze whether aging could also impair angiogenic properties in TAT as in other adipose tissue such as subcutaneous (subcutaneous adipose tissue (SAT)). SAT and TAT specimens were obtained from 35 patients undergoing cardiac surgery, making these tissues readily available as a prime source of adipose tissue. Patients were separated into two age-dependent groups; middle-aged (n = 18) and elderly (n = 17). Angiogenic, endothelial, and adipogenic expression markers were analyzed in both tissues from each group and correlations were examined between these parameters and also with age. There were no significant differences in subjects from either group in clinical or biological variables. Angiogenic markers VEGF-A, B, C, and D and adipogenic parameters, peroxisome proliferator-activated receptors (PPARγ2), FABP4, and ADRP showed elevated expression levels in TAT from elderly patients compared to the middle-aged group, while in SAT, expression levels of these isoforms were significantly decreased in elderly patients. VEGF-R1, VEGF-R2, VEGF-R3, Thy1, CD31, CD29, and VLA1 showed increased levels in TAT from the elderly compared to the middle-aged, while in SAT these levels displayed a decline with aging. Also, in TAT, angiogenic and endothelial parameters exhibited strong positive correlations with age. TAT appears to be the most appropriate source of angiogenic and endothelial factors in elderly cardiomyopathy subjects compared to SAT.
Clinica Chimica Acta, 2014
The association of androgen excess with abdominal adiposity, insulin resistance and metabolic der... more The association of androgen excess with abdominal adiposity, insulin resistance and metabolic derangements characterize many patients with PCOS. However, the mechanisms underlying these associations are not entirely understood, indicating the need for discovery of the origin of these metabolic alterations, and of new metabolic biomarkers for PCOS. This review summarizes the metabolites and metabolic pathways associated with PCOS according to recent metabolomic studies. PCOS-associated metabolites were involved mostly in carbohydrate, fat, and protein metabolism. Obesity, hyperinsulinemia and the intrinsic heterogeneity of PCOS are responsible of the metabolic variation observed in these women. Furthermore, treatment of PCOS seems to modify the levels of some metabolites. Hopefully, advances in the knowledge of metabolism will allow the detection of systemic imbalances in PCOS and will permit the identification of biomarkers that serve to predict the progression of the disease and its future complications.
Obesity, 2010
Peroxisome proliferator-activated receptor-γ (PPARγ) may play a protective role in the regulation... more Peroxisome proliferator-activated receptor-γ (PPARγ) may play a protective role in the regulation of vascular function, partly mediated by its effects on superoxide dismutase (SOD). The aim of this study was to determine the association between PPARγ expression in peripheral blood mononuclear cells (PBMCs) and SOD activity in morbidly obese persons with varying degrees of insulin resistance (IR). We studied in 10 morbidly obese persons (five with no IR and five with high IR) the effect of a high-fat meal on the plasma activity of various antioxidant enzymes and the mRNA expression of PPARγ in PBMC. The high-fat meal resulted in a significant decrease in plasma SOD activity, glutathione reductase (GSH-Rd) activity, and mRNA expression of PPARγ only in the group of morbidly obese persons with high IR. PPARγ expression after the high-fat meal correlated with the IR levels (r = −0.803, P = 0.009) and the plasma SOD activity (r = 0.903, P = 0.001). Likewise, the reduction in PPARγ expression correlated with the increase in free fatty acids (FFA) (r = 0.733, P = 0.016). In conclusion, the decreased expression of PPARγ in PBMC in morbidly obese persons after a high-fat meal was associated with the state of IR, the plasma SOD activity, and the changes in the concentration of FFA.
Obesity Surgery, Mar 1, 2010
The prevalence of morbid obesity has seen an increase in developed countries over recent years. B... more The prevalence of morbid obesity has seen an increase in developed countries over recent years. Bariatric surgery is almost the only effective strategy for treating super morbidly obese patients. The objective of the study was to evaluate the effects of bariatric surgery on the evolution of the main variables related to diabetes and obesity, especially insulin resistance, parameters of oxidative stress, and inflammatory markers in the early stage after surgery. The study was undertaken in 17 morbidly obese persons who were scheduled for biliopancreatic diversion of Scopinaro. Measurements were made before surgery and 15, 30, 45, and 90 days after surgery. We found that significant metabolic changes occurred during the first 90 days after bariatric surgery. The most significant decrease in insulin resistance occurred 15 days after the operation. At this point, the lipid profile and inflammatory and oxidative stress parameters had not improved. One month after surgery, insulin resistance had a parallel evolution to weight and the molecules directly associated with hypertrophic adipose tissue. We suggest that there are two mechanisms that contribute to the improvement in insulin resistance after biliopancreatic diversion: on the one hand, a short-term effect related to gastric bypass, and on the other hand, a long-term effect from decreased fat mass and resulting changes in the release of molecules directly associated with hypertrophic adipose tissue.
Atherosclerosis Supplements, 2010
Atherosclerosis Supplements, 2009
Introduction: Oxidative stress play an important role in the pathogenesis of the metabolic syndro... more Introduction: Oxidative stress play an important role in the pathogenesis of the metabolic syndrome. Hypertriglyceridemia is a component of the metabolic syndrome that is associated with increased oxidative stress. Material and Methods: 17 controls and two groups with hypertriglyceridemia: 43 without the metabolic syndrome and 29 with the metabolic syndrome. All subjects underwent a 60 g fat overload. Baseline measurements included glucose, body mass index, waist circumference and homeostasis model assessment insulin resistance. Cholesterol, triglycerides, HDL cholesterol, TNF-alpha and IL-6, lipoperoxide, carbonylated proteins, reduced glutathione, oxidized glutathione, glutathione peroxidase, glutathione reductase, catalase and glutathione transferase were measured at baseline and 3 h after fat overload. Results: Compared to the controls, the two patient groups had higher plasma levels at baseline and after overload of cholesterol, triglycerides and apolipoprotein B, lipoperoxide, carbonylated proteins and oxidized glutathione, and lower levels of antioxidants at baseline and after the fat overload. Conclusion: The two patients groups had the same degree of oxidative stress.
Clinical laboratory, 2010
Several indirect techniques have been used for measuring oxidative stress in sleep apnoea-hypopno... more Several indirect techniques have been used for measuring oxidative stress in sleep apnoea-hypopnoea syndrome (SAHS) patients. The purpose of this study was to find out if both, cellular or plasma oxidative stress evaluations, are good estimators to assess oxidative stress in SAHS patients before and after one month's CPAP treatment. The study included 28 SAHS patients requiring CPAP treatment and 15 healthy control subjects. Plasma and serum oxidative stress biomarkers (lipid peroxidation, total antioxidant capacity, and the activities of glutathione peroxidase, glutathione reductase, glutathione s-transferase, catalase and superoxide dismutase) were measured using commercial kits. Cellular oxidative stress biomarkers (mitochondrial membrane potential, intracellular glutathione, superoxide anion, and hydrogen peroxide) were analysed by flow cytometry. The Wilcoxon test for paired samples was used to compare oxidative stress and clinical parameters in patients before and after tr...
High Blood Pressure & Cardiovascular Prevention, 2007
High sCRP is considered a non-traditional risk factor for CV morbidity and mortality. Aims of thi... more High sCRP is considered a non-traditional risk factor for CV morbidity and mortality. Aims of this study were the validation of both the reliability of high sCRP as predictor of global and CV mortality and the associations between sCRP ad other proxies of CV risk. Methods: We studied the patients admitted to our Renal Unit from 1/1/2000 to 12/31/2001. During the hospital stay the following parameters were assessed: measured creatinine clearance (CrCl), haemoglobin (hb), haematocrit (hct), sCRP (high-sensitive method), serum levels of uric acid (UA), total cholesterol (chol), triglycerides (try) and total proteins (prot). Thus data about the survival of the patients were recorded at the study end date (12/31/2006). Patients with end stage renal disease, sepsis or those taking steroids or NSAIDs were excluded. Results: We studied 233 patients (46.3% males, 16.3% diabetics, 9% taking statins), aged [mean(SD)] 55.7(18.2) years. Means(SD) of the other parameters were: hb 13.4(1.7) g/dl, hct 39.8(4.3)%, UA 5.3(1.8) mg/dl, prot 6.8(0.6) g/dl, chol 193.8(43.4) mg/dl, try 145.1(107) mg/dl, CrCl 67.5(35) ml/min. Thus the patients were subdivided according to the sCRP quartiles (PLa ClCr and Prot progressively decreased among quartiles. UA significantly correlated with sPCR levels in the whole population Spearman analysis) (R=0,15; P=0,009). The presence of diabetes mellitus or lipid-lowering therpy do not significatly modify these data. Conclusions: 1) high sCRP does not predict 5-year global and cardiovascular mortality; 2) ClCr and Prot have not been significantly related to hsCRP levels; 3) values of sCRP 7 mg/L have been associated to reduced levels of HGB, HCT, CHOL and high levels of UA; 4) UA has been sifnificantly dorelated to sCRP in the whole population.
Biological Trace Element Research, 2011
Background: Stress from obstructive sleep apnoea (OSA) stimulates catecholamine release and conse... more Background: Stress from obstructive sleep apnoea (OSA) stimulates catecholamine release and consequently can exacerbate hypertension, even in the absence of a catecholamine-producing tumour (phaeochromocytoma). As such, a positive screening test for suspected phaeochromocytoma may be misleading. There exists only a handful case reports, and no controlled trials, how continuous positive airway pressure (CPAP) to treat OSA influences catecholamine levels. We examined changes to levels of urinary catecholamine and blood pressure in response to CPAP treatment. Methods: We conducted a meta-analysis of data aggregated from published case reports of individual patient data up to April 2020. The quality of the reports was evaluated using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. Results: A total of 13 cases (seven men and six women) from seven reports met our search criteria. Patients had mean age of 49.1 years (range ¼ 36-62) and body mass index of 37.4 kg/m 2 (range ¼ 27-56). Most had moderate to severe OSA with CPAP treatment. Nine cases had 24-hour urinary noradrenaline assessment before and after CPAP treatment. CPAP treatment led to a 21% reduction (104 nmol/24-hours, 95% credible interval ¼59 to 148) in 24-hour urinary noradrenaline to within reference ranges, and 25% reduction (from 131 to 100 mmHg) in mean arterial pressure. The risk of overall bias evaluated by the ROBINS-I tool was found to be low in the majority of reports. Conclusions: Investigations of patients suspected of phaeochromocytoma, particularly obese individuals, should exclude OSA and treat this condition if present before performing screening tests to assess for catecholamine levels.
Diabetes Care
OBJECTIVE: Cell death determines the onset of obesity and associated insulin resistance. Here, we... more OBJECTIVE: Cell death determines the onset of obesity and associated insulin resistance. Here, we analyze the relationship among obesity, adipose tissue apoptosis, and insulin signaling. RESEARCH DESIGN AND METHODS: The expression levels of initiator (CASP8/9) and effector (CASP3/7) caspases as well as antiapoptotic B-cell lymphoma (BCL)2 and inflammatory markers were assessed in visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with different degrees of obesity and without insulin resistance or diabetes. Adipose tissue explants from lean subjects were cultured with TNF-a or IL-6, and the expression of apoptotic and insulin signaling components was analyzed and compared with basal expression levels in morbidly obese subjects. RESULTS SAT and VAT exhibited increased CASP3/7 and CASP8/9 expression levels and decreased BCL2 expression with BMI increase. These changes were accompanied by increased inflammatory cytokine mRNA levels and macrophage infiltration markers. In...
Surgery for Obesity and Related Diseases, 2012
Obesity is very often accompanied by other diseases, with the most common type 2 diabetes mellitu... more Obesity is very often accompanied by other diseases, with the most common type 2 diabetes mellitus and cardiovascular complications. Bariatric surgery is the most effective strategy for treating morbidly obese patients. We evaluated the metabolic changes that occur in the early stage after 2 types of bariatric surgery, biliopancreatic diversion of Scopinaro (BPD) and sleeve gastrectomy (SG), in morbidly obese patients. The study was undertaken in 31 nondiabetic morbidly obese patients (7 men and 24 women). Of the 31 patients, 18 underwent BPD and 13 underwent SG. All patients were examined before bariatric surgery (baseline) and at 15, 30, 45, and 90 days postoperatively. Significant improvement occurred in the anthropometric variables after the 2 types of bariatric surgery, without significant differences between the 2 types of interventions. In patients undergoing BPD, the serum glucose, cholesterol, triglycerides, high-density lipoprotein cholesterol, and free fatty acids were significantly reduced. The changes that occurred in these biochemical variables after SG were not significant. Insulin resistance decreased significantly during the 90 days after surgery, with the greatest decrease at 15 days. However, in the patients who underwent SG, insulin resistance worsened at 15 days and later diminished. The results of the present study have shown that the surgical technique that excludes the duodenum (i.e., BPD) has immediate postoperative changes in the degree of insulin resistance in morbidly obese patients compared to those techniques that do not exclude the duodenum (i.e., SG).
Molecular and Cellular Endocrinology, 2013
The mechanisms involved in the progression to overt diabetes in pre-obese subjects remain unclear... more The mechanisms involved in the progression to overt diabetes in pre-obese subjects remain unclear. Therefore, a nontargeted evaluation of differences in the protein abundance of visceral adipose tissue (VAT) obtained from pre-obese diabetic subjects and pre-obese subjects showing normal glucose tolerance may provide novel insights on the molecular processes involved in the progression to overt diabetes in pre-obesity. Diabetic patients showed increased VAT abundance of glutathione S-transferase Mu 2, peroxiredoxin-2, antithrombin-III, apolipoprotein A-IV, Ig j chain C region, mitochondrial aldehyde dehydrogenase and actin, and decreased abundance of annexin-A1, retinaldehyde dehydrogenase-1, and vinculin, compared with their non-diabetic counterparts. These proteins are involved in cytoskeleton function and structure, oxidative stress, inflammation and retinoid metabolism. The presence of diabetes influences the VAT abundance of several proteins. Hence, the proteins identified here could be considered candidate molecules in future studies addressing the role that VAT dysfunction plays in the development of type 2 diabetes.
Journal of Agricultural and Food Chemistry, 2013
Human Reproduction Update, 2013
background: Oxidative stress might be associated with polycystic ovary syndrome (PCOS), but relat... more background: Oxidative stress might be associated with polycystic ovary syndrome (PCOS), but relatively small studies published to date do not permit reaching a definitive conclusion. We aimed at conducting a systematic review and meta-analysis of studies evaluating circulating markers of oxidative stress in patients with PCOS. methods: We conducted a systematic review of studies reporting circulating markers of oxidative stress in women with PCOS and controls published up to June 2012, using Entrez PubMed and EMBASE online facilities. Meta-analysis calculated standardized mean differences (SMDs) and 95% confidence intervals (95CI). results: From 1633 potential studies identified electronically, 68 studies, including 4933 PCOS patients and 3671 controls, were selected. For each of nine circulating markers of oxidative stress, an individual meta-analysis was conducted. Compared with control women, patients with PCOS presented higher circulating concentrations of homocysteine (23% increase, SMD 0.6, 95CI, 0.4-0.8), malondialdehyde (47% increase, SMD 1.9, 95CI 1.2-2.6) and asymmetric dimethylarginine (36% increase, SMD 1.1, 95CI 0.6-1.6), and increased superoxide dismutase activity (34% increase, SMD 1.0, 95CI 0.5-1.4) and decreased glutathione levels (50% decrease, SMD 23.7, 95CI 26.2 to 21.2) and paraoxonase-1 activity (32% decrease, SMD 20.9, 95CI 21.3 to 20.4). Similar results were found when restricting the analyses to studies in which patients and controls were matched for age and body mass index. conclusions: Circulating markers of oxidative stress are abnormal in women with PCOS independent of weight excess. This finding suggests that oxidative stress may participate in the pathophysiology of this common disorder.
Diabetes Care, 2013
OBJECTIVEdCell death determines the onset of obesity and associated insulin resistance. Here, we ... more OBJECTIVEdCell death determines the onset of obesity and associated insulin resistance. Here, we analyze the relationship among obesity, adipose tissue apoptosis, and insulin signaling.
Current Pharmaceutical Design, 2013
Chronic low-grade subclinical inflammation has been increasingly recognized as an interposer in t... more Chronic low-grade subclinical inflammation has been increasingly recognized as an interposer in the endocrine, metabolic and reproductive disturbances that characterize the polycystic ovary syndrome (PCOS). Abdominal adiposity and obesity are often present in PCOS. Mounting evidence indicates that adipose tissue is involved in innate and adaptive immune responses. Continuous release of inflammatory mediators such as cytokines, acute phase proteins, and adipokines perpetuates the inflammatory condition associated with obesity in women with PCOS, possibly contributing to insulin resistance and other long-term cardiometabolic risk factors. Genetic variants in the genes encoding inflammation-related mediators underlie the development of PCOS and their interaction with environmental factors may contribute to the heterogeneous clinical phenotype of this syndrome. In the future, strategies ameliorating inflammation may prove useful for the management of PCOS and associated conditions.
Clinical Nutrition Supplements, 2008
The American Journal of Clinical Nutrition, 2012
Background: Few studies have investigated the effect of dietary polyphenols on the complex human ... more Background: Few studies have investigated the effect of dietary polyphenols on the complex human gut microbiota, and they focused mainly on single polyphenol molecules and select bacterial populations. Objective: The objective was to evaluate the effect of a moderate intake of red wine polyphenols on select gut microbial groups implicated in host health benefits. Design: Ten healthy male volunteers underwent a randomized, crossover, controlled intervention study. After a washout period, all of the subjects received red wine, the equivalent amount of dealcoholized red wine, or gin for 20 d each. Total fecal DNA was submitted to polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis and real-time quantitative PCR to monitor and quantify changes in fecal microbiota. Several biochemical markers were measured. Results: The dominant bacterial composition did not remain constant over the different intake periods. Compared with baseline, the daily consumption of red wine polyphenol for 4 wk significantly increased the number of Enterococcus, Prevotella, Bacteroides, Bifidobacterium, Bacteroides uniformis, Eggerthella lenta, and Blautia coccoides-Eubacterium rectale groups (P , 0.05). In parallel, systolic and diastolic blood pressures and triglyceride, total cholesterol, HDL cholesterol, and C-reactive protein concentrations decreased significantly (P , 0.05). Moreover, changes in cholesterol and C-reactive protein concentrations were linked to changes in the bifidobacteria number. Conclusion: This study showed that red wine consumption can significantly modulate the growth of select gut microbiota in humans, which suggests possible prebiotic benefits associated with the inclusion of red wine polyphenols in the diet. This trial was registered at controlled-trials.com as ISRCTN88720134.
AGE, 2013
Aging negatively affects angiogenesis which is found to be linked to declined vascular endothelia... more Aging negatively affects angiogenesis which is found to be linked to declined vascular endothelial growth factor (VEGF) production. Adult human thymus degenerates into fat tissue (thymus adipose tissue (TAT)). Recently, we described that TAT from cardiomyopathy ischemic subjects has angiogenic properties. The goal of our study was to analyze whether aging could also impair angiogenic properties in TAT as in other adipose tissue such as subcutaneous (subcutaneous adipose tissue (SAT)). SAT and TAT specimens were obtained from 35 patients undergoing cardiac surgery, making these tissues readily available as a prime source of adipose tissue. Patients were separated into two age-dependent groups; middle-aged (n = 18) and elderly (n = 17). Angiogenic, endothelial, and adipogenic expression markers were analyzed in both tissues from each group and correlations were examined between these parameters and also with age. There were no significant differences in subjects from either group in clinical or biological variables. Angiogenic markers VEGF-A, B, C, and D and adipogenic parameters, peroxisome proliferator-activated receptors (PPARγ2), FABP4, and ADRP showed elevated expression levels in TAT from elderly patients compared to the middle-aged group, while in SAT, expression levels of these isoforms were significantly decreased in elderly patients. VEGF-R1, VEGF-R2, VEGF-R3, Thy1, CD31, CD29, and VLA1 showed increased levels in TAT from the elderly compared to the middle-aged, while in SAT these levels displayed a decline with aging. Also, in TAT, angiogenic and endothelial parameters exhibited strong positive correlations with age. TAT appears to be the most appropriate source of angiogenic and endothelial factors in elderly cardiomyopathy subjects compared to SAT.
Clinica Chimica Acta, 2014
The association of androgen excess with abdominal adiposity, insulin resistance and metabolic der... more The association of androgen excess with abdominal adiposity, insulin resistance and metabolic derangements characterize many patients with PCOS. However, the mechanisms underlying these associations are not entirely understood, indicating the need for discovery of the origin of these metabolic alterations, and of new metabolic biomarkers for PCOS. This review summarizes the metabolites and metabolic pathways associated with PCOS according to recent metabolomic studies. PCOS-associated metabolites were involved mostly in carbohydrate, fat, and protein metabolism. Obesity, hyperinsulinemia and the intrinsic heterogeneity of PCOS are responsible of the metabolic variation observed in these women. Furthermore, treatment of PCOS seems to modify the levels of some metabolites. Hopefully, advances in the knowledge of metabolism will allow the detection of systemic imbalances in PCOS and will permit the identification of biomarkers that serve to predict the progression of the disease and its future complications.
Obesity, 2010
Peroxisome proliferator-activated receptor-γ (PPARγ) may play a protective role in the regulation... more Peroxisome proliferator-activated receptor-γ (PPARγ) may play a protective role in the regulation of vascular function, partly mediated by its effects on superoxide dismutase (SOD). The aim of this study was to determine the association between PPARγ expression in peripheral blood mononuclear cells (PBMCs) and SOD activity in morbidly obese persons with varying degrees of insulin resistance (IR). We studied in 10 morbidly obese persons (five with no IR and five with high IR) the effect of a high-fat meal on the plasma activity of various antioxidant enzymes and the mRNA expression of PPARγ in PBMC. The high-fat meal resulted in a significant decrease in plasma SOD activity, glutathione reductase (GSH-Rd) activity, and mRNA expression of PPARγ only in the group of morbidly obese persons with high IR. PPARγ expression after the high-fat meal correlated with the IR levels (r = −0.803, P = 0.009) and the plasma SOD activity (r = 0.903, P = 0.001). Likewise, the reduction in PPARγ expression correlated with the increase in free fatty acids (FFA) (r = 0.733, P = 0.016). In conclusion, the decreased expression of PPARγ in PBMC in morbidly obese persons after a high-fat meal was associated with the state of IR, the plasma SOD activity, and the changes in the concentration of FFA.
Obesity Surgery, Mar 1, 2010
The prevalence of morbid obesity has seen an increase in developed countries over recent years. B... more The prevalence of morbid obesity has seen an increase in developed countries over recent years. Bariatric surgery is almost the only effective strategy for treating super morbidly obese patients. The objective of the study was to evaluate the effects of bariatric surgery on the evolution of the main variables related to diabetes and obesity, especially insulin resistance, parameters of oxidative stress, and inflammatory markers in the early stage after surgery. The study was undertaken in 17 morbidly obese persons who were scheduled for biliopancreatic diversion of Scopinaro. Measurements were made before surgery and 15, 30, 45, and 90 days after surgery. We found that significant metabolic changes occurred during the first 90 days after bariatric surgery. The most significant decrease in insulin resistance occurred 15 days after the operation. At this point, the lipid profile and inflammatory and oxidative stress parameters had not improved. One month after surgery, insulin resistance had a parallel evolution to weight and the molecules directly associated with hypertrophic adipose tissue. We suggest that there are two mechanisms that contribute to the improvement in insulin resistance after biliopancreatic diversion: on the one hand, a short-term effect related to gastric bypass, and on the other hand, a long-term effect from decreased fat mass and resulting changes in the release of molecules directly associated with hypertrophic adipose tissue.
Atherosclerosis Supplements, 2010
Atherosclerosis Supplements, 2009
Introduction: Oxidative stress play an important role in the pathogenesis of the metabolic syndro... more Introduction: Oxidative stress play an important role in the pathogenesis of the metabolic syndrome. Hypertriglyceridemia is a component of the metabolic syndrome that is associated with increased oxidative stress. Material and Methods: 17 controls and two groups with hypertriglyceridemia: 43 without the metabolic syndrome and 29 with the metabolic syndrome. All subjects underwent a 60 g fat overload. Baseline measurements included glucose, body mass index, waist circumference and homeostasis model assessment insulin resistance. Cholesterol, triglycerides, HDL cholesterol, TNF-alpha and IL-6, lipoperoxide, carbonylated proteins, reduced glutathione, oxidized glutathione, glutathione peroxidase, glutathione reductase, catalase and glutathione transferase were measured at baseline and 3 h after fat overload. Results: Compared to the controls, the two patient groups had higher plasma levels at baseline and after overload of cholesterol, triglycerides and apolipoprotein B, lipoperoxide, carbonylated proteins and oxidized glutathione, and lower levels of antioxidants at baseline and after the fat overload. Conclusion: The two patients groups had the same degree of oxidative stress.
Clinical laboratory, 2010
Several indirect techniques have been used for measuring oxidative stress in sleep apnoea-hypopno... more Several indirect techniques have been used for measuring oxidative stress in sleep apnoea-hypopnoea syndrome (SAHS) patients. The purpose of this study was to find out if both, cellular or plasma oxidative stress evaluations, are good estimators to assess oxidative stress in SAHS patients before and after one month's CPAP treatment. The study included 28 SAHS patients requiring CPAP treatment and 15 healthy control subjects. Plasma and serum oxidative stress biomarkers (lipid peroxidation, total antioxidant capacity, and the activities of glutathione peroxidase, glutathione reductase, glutathione s-transferase, catalase and superoxide dismutase) were measured using commercial kits. Cellular oxidative stress biomarkers (mitochondrial membrane potential, intracellular glutathione, superoxide anion, and hydrogen peroxide) were analysed by flow cytometry. The Wilcoxon test for paired samples was used to compare oxidative stress and clinical parameters in patients before and after tr...
High Blood Pressure & Cardiovascular Prevention, 2007
High sCRP is considered a non-traditional risk factor for CV morbidity and mortality. Aims of thi... more High sCRP is considered a non-traditional risk factor for CV morbidity and mortality. Aims of this study were the validation of both the reliability of high sCRP as predictor of global and CV mortality and the associations between sCRP ad other proxies of CV risk. Methods: We studied the patients admitted to our Renal Unit from 1/1/2000 to 12/31/2001. During the hospital stay the following parameters were assessed: measured creatinine clearance (CrCl), haemoglobin (hb), haematocrit (hct), sCRP (high-sensitive method), serum levels of uric acid (UA), total cholesterol (chol), triglycerides (try) and total proteins (prot). Thus data about the survival of the patients were recorded at the study end date (12/31/2006). Patients with end stage renal disease, sepsis or those taking steroids or NSAIDs were excluded. Results: We studied 233 patients (46.3% males, 16.3% diabetics, 9% taking statins), aged [mean(SD)] 55.7(18.2) years. Means(SD) of the other parameters were: hb 13.4(1.7) g/dl, hct 39.8(4.3)%, UA 5.3(1.8) mg/dl, prot 6.8(0.6) g/dl, chol 193.8(43.4) mg/dl, try 145.1(107) mg/dl, CrCl 67.5(35) ml/min. Thus the patients were subdivided according to the sCRP quartiles (PLa ClCr and Prot progressively decreased among quartiles. UA significantly correlated with sPCR levels in the whole population Spearman analysis) (R=0,15; P=0,009). The presence of diabetes mellitus or lipid-lowering therpy do not significatly modify these data. Conclusions: 1) high sCRP does not predict 5-year global and cardiovascular mortality; 2) ClCr and Prot have not been significantly related to hsCRP levels; 3) values of sCRP 7 mg/L have been associated to reduced levels of HGB, HCT, CHOL and high levels of UA; 4) UA has been sifnificantly dorelated to sCRP in the whole population.
Biological Trace Element Research, 2011
Background: Stress from obstructive sleep apnoea (OSA) stimulates catecholamine release and conse... more Background: Stress from obstructive sleep apnoea (OSA) stimulates catecholamine release and consequently can exacerbate hypertension, even in the absence of a catecholamine-producing tumour (phaeochromocytoma). As such, a positive screening test for suspected phaeochromocytoma may be misleading. There exists only a handful case reports, and no controlled trials, how continuous positive airway pressure (CPAP) to treat OSA influences catecholamine levels. We examined changes to levels of urinary catecholamine and blood pressure in response to CPAP treatment. Methods: We conducted a meta-analysis of data aggregated from published case reports of individual patient data up to April 2020. The quality of the reports was evaluated using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. Results: A total of 13 cases (seven men and six women) from seven reports met our search criteria. Patients had mean age of 49.1 years (range ¼ 36-62) and body mass index of 37.4 kg/m 2 (range ¼ 27-56). Most had moderate to severe OSA with CPAP treatment. Nine cases had 24-hour urinary noradrenaline assessment before and after CPAP treatment. CPAP treatment led to a 21% reduction (104 nmol/24-hours, 95% credible interval ¼59 to 148) in 24-hour urinary noradrenaline to within reference ranges, and 25% reduction (from 131 to 100 mmHg) in mean arterial pressure. The risk of overall bias evaluated by the ROBINS-I tool was found to be low in the majority of reports. Conclusions: Investigations of patients suspected of phaeochromocytoma, particularly obese individuals, should exclude OSA and treat this condition if present before performing screening tests to assess for catecholamine levels.