Metabolic endotoxemia promotes adipose dysfunction and inflammation in human obesity.

Impaired adipose tissue (AT) lipid handling and inflammation is associated with obesity-related metabolic diseases. Circulating lipopolysaccharides (LPSs) from gut microbiota (metabolic endotoxemia), proposed as a triggering factor for the low-grade inflammation in obesity, might also be responsible for AT dysfunction. Nevertheless, this hypothesis has not been explored in human obesity. To analyze the relationship between metabolic endotoxemia and AT markers for lipogenesis, lipid handling, and inflammation in human obesity, 33 patients with obesity scheduled for surgery were recruited and classified according to their LPS levels. Visceral and subcutaneous AT gene and protein expression were analyzed and adipocyte and AT in vitro assays performed. Subjects with obesity with a high degree of metabolic endotoxemia had lower expression of key genes for AT function and lipogenesis ( SREBP1, FABP4, FASN, and LEP) but higher expression of inflammatory genes in visceral and subcutaneous AT than subjects with low LPS levels. In vitro experiments corroborated that LPS are responsible for adipocyte and AT inflammation and downregulation of PPARG, SCD, FABP4, and LEP expression and LEP secretion. Thus, metabolic endotoxemia influences AT physiology in human obesity by decreasing the expression of factors involved in AT lipid handling and function as well as by increasing inflammation.

New molecular biomarkers in differentiated thyroid carcinoma: Impact of miR-146, miR-221 and miR-222 levels in the evolution of the disease.

OBJECTIVE: MircroRNAs (miR) are small, noncoding RNA molecules of 18-25 nucleotides. Their dysregulation has been widely studied in many human tumours including differentiated thyroid cancer (DTC). miRs more frequently associated with these kinds of tumours are miR-146, miR-221 and miR-222. Our objective was to assess the relationship among circulating miR levels and the evolution and outcomes of disease. DESIGN: We analysed a sample of 60 patients with DTC assigning them to one of three groups according to the dynamic scale of risk (excellent response, incomplete biochemical response and incomplete structural response). PATIENTS AND MEASUREMENTS: At study inclusion, we determined thyroid-stimulating hormone, thyroxine, thyroglobulin, antithyroglobulin antibodies and plasma levels of miR-146, miR-221 and miR-222. RESULTS: Male sex and advanced age at diagnosis were associated with the worst disease progression. miR-222 was twofold to threefold higher in tall cell papillary carcinomas (P = 0.038). miR-146 (P = 0.016) and miR-221 (P = 0.050) had a positive correlation with thyroglobulin at the time of sampling. In regression analysis, miR-146 (P = 0.006), miR-221 (P = 0.004) and miR-222 (P = 0.007) predicted more than 70% of the variation in thyroglobulin levels at the time of sampling. CONCLUSIONS: Elevated miR-222 and miR-146 levels are associated with poorer outcomes of the disease and may have a prognostic value in the management and follow-up of DTC.

Adipose Tissue LPL Methylation is Associated with Triglyceride Concentrations in the Metabolic Syndrome.

BACKGROUND: DNA methylation is one of the epigenetic mechanisms that regulate gene expression. DNA methylation may be modified by environmental and nutritional factors. Thus, epigenetics could potentially provide a mechanism to explain the etiology of metabolic disorders, such as metabolic syndrome (MetS). The aim of this study was to analyze the level of DNA methylation of several lipoprotein lipase (LPL)-promoter-CpG dinucleotides in a CpG island region and relate this to the gene and protein expression levels in human visceral adipose tissue (VAT) from individuals with and without MetS. METHODS: VAT samples were collected from laparoscopic surgical patients without and with MetS, and levels of LPL mRNA, LPL protein, and LPL DNA methylation were measured by qPCR, western blot, and pyrosequencing. Biochemical and anthropometric variables were analyzed. Individuals included in a subset underwent a dietary fat challenge test, and levels of postprandial triglycerides were determined. RESULTS: We found higher levels of DNA methylation in MetS patients but lower gene expression and protein levels. There was a negative association between LPL methylation and LPL gene expression. We found a positive association between LPL methylation status and abnormalities of the metabolic profile and basal and postprandial triglycerides, whereas LPL gene expression was negatively associated with these abnormalities. CONCLUSIONS: We demonstrate that LPL methylation may be influenced by the degree of metabolic disturbances and could be involved in triglyceride metabolism, promoting hypertriglyceridemia and subsequent associated disorders, such as MetS.

PDE5A Polymorphisms Influence on Sildenafil Treatment Success.

INTRODUCTION: Diabetes and cardiovascular disease are risk factors for erectile dysfunction (ED). Selective inhibitors of the type 5 phosphodiesterase are the first option for treating ED. However, it is unknown why there are patients with low response to this treatment. Polymorphisms in the PDE5A gene may influence the response to PDE5 inhibitors treatment. AIM: The aim of this study is to analyze the relationship between PDE5A polymorphisms, diabetes, and the efficacy of sildenafil treatment. METHODS: A Spanish prospective cohort of 170 Caucasian male patients diagnosed with ED and ischemic heart disease treated with angioplasty was studied. MAIN OUTCOME MEASURES: ED was evaluated according to the 5-item version of the International Index for Erectile Function before and after treatment with sildenafil 50 mg. The gene sequence of the PDE5A gene was analyzed for the presence of rs12646525 and rs3806808 polymorphisms. Glucose and glycosylated hemoglobin levels were measured in blood serum samples. The relationship between treatment response, genotype, and glycemic status was analyzed. RESULTS: Patients with G-allele of rs3806808 polymorphism showed a worse response to the treatment compared to TT-homozygote patients. Nondiabetic G-allele carriers showed a worse treatment response than TT-homozygotes patients. These differences were not seen in diabetic patients. There were no significant differences in treatment response according to the rs12646525 polymorphism in total population or according to the glycemic status. Logistic regression analysis showed that nondiabetic carriers of the major allele of both the rs12646525 and rs3806808 polymorphism had a significantly higher likelihood to respond to the treatment than diabetic patients carriers of the minor allele (P < .05). CONCLUSION: The response to sildenafil treatment depends on polymorphisms in the PDE5A gene and the glycemic status of the patients.

Predictive Role of Gut Microbiota in Weight Loss Achievement after Bariatric Surgery.

BACKGROUND: Bariatric surgery induces changes in gut microbiota that have been suggested to contribute to weight loss and metabolic improvement. However, whether preoperative gut microbiota composition could predict response to bariatric surgery has not yet been elucidated. STUDY DESIGN: Seventy-six patients who underwent sleeve gastrectomy were classified according to the percentage of excess weight loss (%EWL) 1 year after surgery in the responder group: >50%EWL (n=50) and the nonresponder group: <50%EWL (n=26). Patients were evaluated before surgery, and 3 months and 1 year after surgery. Gut microbiota composition was analyzed before surgery (n=76) and 3 months after bariatric surgery (n=40). RESULTS: Diversity analysis did not show differences between groups before surgery or 3 months after surgery. Before surgery, there were differences in the abundance of members belonging to Bacteroidetes and Firmicutes phyla (nonresponder group: enriched in Bacteroidaceae, Bacteroides, Bacteroides uniformis, Alistipes finegoldii, Alistipes alistipes, Dorea formicigenerans, and Ruminococcus gnavus. Responder group: enriched in Peptostreptococcaceae, Gemmiger, Gemiger formicilis, Barnesiella, Prevotellaceae, and Prevotella; linear discriminant analysis >2; p < 0.05). Prevotella-to-Bacteroides ratio was significantly lower in the nonresponder group compared to the responder group (p = 0.048). After surgery, the responder group showed an enrichment in taxa that have been shown to have beneficial effects on host metabolism. Before surgery, PICRUSt analysis showed an enrichment in pathways involved in the biosynthesis components of the O-antigen polysaccharideunits in lipopolysaccharides in the nonresponder group. CONCLUSIONS: Preoperative gut microbiota could have an impact on bariatric surgery outcomes. Prevotella-to-Bacteroides ratio could be used as a predictive tool for weight loss trajectory. Early after surgery, patients who experienced successful weight loss showed an enrichment in taxa related to beneficial effects on host metabolism.

Prevalence of and risk factors for erectile dysfunction in young nondiabetic obese men: results from a regional study.

Erectile dysfunction (ED), a condition closely related to cardiovascular morbidity and mortality, is frequently associated with obesity. In this study, we aimed to determine the prevalence of ED and evaluate the associated risk factors in a cohort of 254 young (18-49 years) nondiabetic obese (body mass index [BMI] ≥ 30 kg m-2) men from primary care. Erectile function (International Index of Erectile Function [IIEF-5] questionnaire), quality of life (Aging Males' Symptoms [AMS scale]), and body composition analysis (Tanita MC-180MA) were determined. Total testosterone was determined using high-performance liquid chromatography-mass spectrometry. Multivariate logistic regression analysis was used to study the factors associated with ED. ED prevalence was 42.1%. Subjects with ED presented higher BMI, waist circumference, number of components of the metabolic syndrome, AMS score, insulin resistance, and a more unfavorable body composition than those without ED. Multivariate logistic regression analysis showed that a pathological AMS score (odds ratio [OR]: 4.238, P < 0.001), degree of obesity (BMI ≥ 40 kg m-2, OR: 2.602, P = 0.005, compared with BMI 30-34.9 kg m-2), high-density lipoprotein (HDL)-cholesterol levels (OR: 0.956, P = 0.004), and age (OR: 1.047, P = 0.016) were factors independently associated with ED. In conclusion, we demonstrate that, in a primary care-based cohort of nondiabetic young obese men, ED affected >40% of subjects. A pathological AMS score, the degree of obesity, and age were positively associated with ED, while elevated HDL-cholesterol levels were inversely associated with the odds of presenting ED. Further prospective studies are needed to evaluate the long-term consequences of ED in this population.

Renal and Neurologic Benefit of Levosimendan vs Dobutamine in Patients With Low Cardiac Output Syndrome After Cardiac Surgery: Clinical Trial FIM-BGC-2014-01.

BACKGROUND: Low-cardiac output syndrome (LCOS) after cardiac surgery secondary to systemic hypoperfusion is associated with a higher incidence of renal and neurological damage. A range of effective therapies are available for LCOS. The beneficial systemic effects of levosimendan persist even after cardiac output is restored, which suggests an independent cardioprotective effect. METHODS: A double-blind clinical trial was conducted in patients with a confirmed diagnosis of LCOS randomized into two treatment groups (levosimendan vs. dobutamine). Monitoring of hemodynamic (cardiac index, systolic volume index, heart rate, mean arterial pressure, central venous pressure, central venous saturation); biochemical (e.g. creatinine, S100B protein, NT-proBNP, troponin I); and renal parameters was performed using acute kidney injury scale (AKI scale) and renal and brain ultrasound measurements [vascular resistance index (VRI)] at diagnosis and during the first 48 h. RESULTS: Significant differences were observed between groups in terms of cardiac index, systolic volume index, NT-proBNP, and kidney injury stage at diagnosis. In the levosimendan group, there were significant variations in AKI stage after 24 and 48 h. No significant differences were observed in the other parameters studied. CONCLUSION: Levosimendan showed a beneficial effect on renal function in LCOS patients after cardiac surgery that was independent from cardiac output and vascular tone. This effect is probably achieved by pharmacological postconditioning. CLINICAL TRIAL REGISTRATION: EUDRA CT, identifier 2014-001461-27. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001461-27.

Effect of Synbiotic Supplementation in a Very-Low-Calorie Ketogenic Diet on Weight Loss Achievement and Gut Microbiota: A Randomized Controlled Pilot Study.

SCOPE: Little is known about the changes that a very-low-calorie ketogenic diet (VLCKD) produces in gut microbiota or the effect of synbiotics during the diet. The aim of this study is to evaluate changes in gut microbiota produced by a VLCKD and synbiotic supplementation. METHODS AND RESULTS: A randomized, single-blind, parallel-design trial is conducted in 33 obese patients who follow a weight-loss program (PnK-Method) that include a VLCKD followed by a low-calorie diet (LCD). Subjects are randomly allocated to three groups: one supplemented with synbiotics, a second group supplemented with a placebo during the VLCKD and synbiotics during the LCD phase, and a control group given a placebo. Although symbiotic administration do not produce an effect on microbial diversity, an increase in short-chain fatty aciding producing bacteria and anti-inflammatory mediator signals such as Odoribacter and Lachnospira is shown. The administration of Bifidobacterium animalis subsp. lactis and prebiotics fiber during the LCD is significantly associated with the percentage of weight loss and change in glucose, C-reactive protein and lipopolysaccharide-binding protein. CONCLUSIONS: VLCKD produces important changes in gut microbiota. The administration of synbiotics during VLCKD can improve weight loss through the amelioration of inflammation, which may be mediated by the gut microbiota.

Altered Adipose Tissue DNA Methylation Status in Metabolic Syndrome: Relationships Between Global DNA Methylation and Specific Methylation at Adipogenic, Lipid Metabolism and Inflammatory Candidate Genes and Metabolic Variables.

Metabolic syndrome (MetS) has been postulated to increase the risk for type 2 diabetes, cardiovascular disease and cancer. Adipose tissue (AT) plays an important role in metabolic homeostasis, and AT dysfunction has an active role in metabolic diseases. MetS is closely related to lifestyle and environmental factors. Epigenetics has emerged as an interesting landscape to evaluate the possible interconnection between AT and metabolic disease, since it can be modulated by environmental factors and metabolic status. The aim of this study was to determine whether MetS has an impact on the global DNA methylation pattern and the DNA methylation of several genes related to adipogenesis (PPARG, PPARA), lipid metabolism (RXRA, SREBF2, SREBF1, SCD, LPL, LXRb), and inflammation (LRP1 C3, LEP and TNF) in visceral adipose tissue. LPL and TNF DNA methylation values were significantly different in the control-case comparisons, with higher and lower methylation respectively in the MetS group. Negative correlations were found between global DNA methylation (measured by LINE-1 methylation levels) and the metabolic deterioration and glucose levels. There were associations among variables of MetS, BMI, and HOMA-IR with DNA methylation at several CpG positions for the studied genes. In particular, there was a strong positive association between serum triglyceride levels (TG) with PPARA and LPL methylation levels. TNF methylation was negatively associated with the metabolic worsening and could be an important factor in preventing MetS occurrence according to logistic regression analysis. Therefore, global DNA methylation and methylation at specific genes related to adipogenesis, lipid metabolism and inflammation are related to the etiology of MetS and might explain in part some of the features associated to metabolic disorders.

Involvement of acetyl-CoA-producing enzymes in the deterioration of the functional potential of adipose-derived multipotent cells from subjects with metabolic syndrome.

OBJECTIVE: The expansion capacity of white adipose tissue influences the distribution of fat depots in the body, the visceral accumulation of which is linked to metabolic syndrome, regardless of the degree of obesity of the subjects. Alterations in the adipose tissue-derived mesenchymal stem cells (ASCs) may contribute to the adipose tissue remodeling associated with metabolic syndrome and impact the regional distribution of adipose tissue by generating inherently dysfunctional adipocytes. Here we examine the expression levels of acetyl-CoA-producing enzymes and their relationship with the lipogenic, antioxidant and oxidative potential of adipocytes generated from visceral ASCs (adipo-visASCs) and subcutaneous ASCs (adipo-subASCs) from subjects with different metabolic profiles. MATERIALS/METHODS: Paired samples of visceral and subcutaneous adipose tissue were processed to isolate the respective ASCs from normal-weight (Nw) subjects and obese patients with metabolic syndrome (METS) and without METS (NonMETS). qPCR was used to quantify the expression levels of the genes studied in both adipo-ASCs from the patient groups and those generated after silencing by small interfering RNA of acetyl-CoA-producing enzymes. The accumulation of lipids was quantified by absorbance. RESULTS: No significant differences in cell yield or CD34+CD31-CD45- ASC percentage were observed between the different patient groups. Unlike adipo-visASCs, adipo-subASCs from METS patients showed a decrease in expression levels of acetyl-CoA-producing enzymes as well as proteins linked to lipogenesis, antioxidant defense and fatty acid oxidation. Transcriptional silencing of acetyl-CoA-producing enzymes in adipo-subASCs reduced lipid accumulation and affected transcription levels of lipogenic and antioxidant defense proteins. CONCLUSIONS: Adipo-subASCs may be more susceptible than adipo-visASCs to deterioration of the lipogenic, oxidative and antioxidant potential associated with metabolic syndrome. Intrinsic alterations in transcription levels of acetyl-CoA-producing enzymes may contribute to the metabolic reprogramming of adipo-subASCs from METS patients.

Differential effects of restrictive and malabsorptive bariatric surgery procedures on the serum lipidome in obese subjects.

BACKGROUND: Bariatric surgery (BS) is the most effective treatment for severe obesity. Our group and others have previously reported that the type of BS (restrictive vs malabsorptive) can lead to different effects on the lipid profile and glucose homeostasis in morbidly obese patients. Furthermore, BS exerts significant changes in lipid metabolism, which are not yet fully understood and that might be dependent of surgical technique. OBJECTIVE: The objective of this study was to evaluate the differential changes in the serum lipidomic profile of morbidly obese subjects who underwent two different BS techniques: sleeve gastrectomy (SG) (restrictive) and biliopancreatic diversion (BPD) (malabsorptive). METHODS: This study included 37 morbidly obese patients (body mass index ≥ 40 kg/m2) who underwent either SG (n = 25) or BPD (n = 12). Serum lipid extracts were assessed at baseline and 6 months after BS and were analyzed in a ultra-high performance liquid chromatography time-of-flight mass spectrometry-based platform. RESULTS: SG not only restores the circulating levels of fatty acids and glycerolipids to similar levels to those observed in nonobese subjects but also results in a consistent increase of phospholipid and sphingolipid species, ranging from antioxidant plasmalogens to lipotoxic ceramides. BPD, however, leads to an overall reduction in circulating fatty acids, glycerolipids, phospholipids and sphingolipids, and a substantial increase of bile acids. CONCLUSION: Our lipidomic analysis suggests that the differential metabolic effects typically observed after restrictive vs malabsorptive BS procedures could be explained, at least partially, to BS-specific lipid changes and provides novel aspects of lipid remodeling in obesity during weight loss.

Neovascular deterioration, impaired NADPH oxidase and inflammatory cytokine expression in adipose-derived multipotent cells from subjects with metabolic syndrome.

OBJECTIVE: Expansion of adipose tissue depends on the growth of its vascular network and it has been shown that adipose tissue dysfunction in obese subjects with the metabolic syndrome is associated with decreased angiogenesis. However, some subjects with a high body mass index do not develop metabolic abnormalities associated with obesity. In this study we examined the neovascular properties, expression levels of proteins involved in cellular redox balance and inflammatory cytokines in adipose-derived multipotent mesenchymal cells (ASCs) of subjects with different metabolic profiles. MATERIALS/METHODS: We applied cell culture, flow cytometry, RT-qPCR and ELISA techniques to characterize the ASCs isolated from paired biopsies of visceral (visASCs) and subcutaneous (subASCs) adipose tissue from 39 subjects grouped into normal weight (Nw), obese without metabolic syndrome (NonMS) and with metabolic syndrome (MS). RESULTS: VisASCs and subASCs from MS subjects showed a decrease in tubules formation capacity compared to ASCs from NonMS subjects as well as changes in the expression levels of proteins involved in cell redox balance and secretion levels of proteins linked to the senescence-associated secretory phenotype. Deterioration in the neovascular properties of subASCs from the MS subjects was also evident in the decreased levels of VEGF secretion during adipogenesis and in the effects of the conditioned medium on endothelial cell tubule formation. CONCLUSIONS: Our findings suggest a redox imbalance status in ASCs from subjects with metabolic syndrome and decreased their neovascular function that probably contributes to the vascular insufficiency of adipose depots.

Different response to hypoxia of adipose-derived multipotent cells from obese subjects with and without metabolic syndrome.

BACKGROUND/OBJECTIVES: Multiple studies suggest that hypoxia, together with inflammation, could be one of the phenomena involved in the onset and progression of obesity-related insulin resistance. In addition, dysfunction of adipose tissue in obese subjects with metabolic syndrome is associated with decreased angiogenesis. However, some subjects with a high body mass index do not develop metabolic abnormalities associated with obesity. The aim of the current study was to examine the neovascular properties of visceral adipose tissue-derived multipotent mesenchymal cells subjected to hypoxia (hypox-visASCs) from normal-weight subjects (Nw) and obese patients with metabolic syndrome (MS) and without metabolic syndrome (NonMS). METHODS: This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. Eight patients who underwent either bariatric surgery or cholecystectomy (27 patients) participated in the study. Visceral adipose tissue samples from Nw, MS and NonMS subjects were processed by enzymatic digestion. VisASCs cultured under hypoxic conditions were characterized by tubule formation assay, ELISA, flow cytometry, migration rate, and qRT-PCR, and the effects of visASCs-conditioned medium on survival and endothelial cell tubule formation were evaluated. RESULTS: Hypox-visASCs from NonMS subjects showed a greater capacity for tubule formation than hypox-visASCs from Nw and MS subjects. The lower percentage of CD140b+/CD44+ and CD140b+/CD184+ cells observed in hypox-visASCs from NonMS subjects compared to MS subjects was accompanied not only by a lower migration rate from the chemotactic effects of stromal cell derived factor 1α, but also by lower levels of NOX5 mRNA expression. While the levels of monocyte chemoattractant protein 1 mRNA expressed by hypox-visASCs correlated positively with the body mass index and waist circumference of the subjects, the concentration of vascular endothelial growth factor present in hypox-visASC-conditioned culture medium decreased significantly with increasing plasma glucose. The survival rate and tubules formed by endothelial cells cultured in hypox-visASC-conditioned medium decreased significantly with increasing homeostasis model assessment to quantify insulin resistance. CONCLUSIONS: Our results suggest that hypox-visASCs from NonMS subjects could promote healthy adipose tissue expansion, while hypox-visASCs from MS subjects appear to contribute to the decreased angiogenic potential and increased inflammation underlying adipose tissue dysfunction in obesity. Our results emphasize the importance of taking into account not only the BMI but also the metabolic profile of the subjects during the implementation of ASCs-based therapy to promote neovascularization.

Smell-taste dysfunctions in extreme weight/eating conditions: analysis of hormonal and psychological interactions.

(1) The objective of this study is to analyze differences in smell-taste capacity between females in extreme weight/eating conditions (EWC) and (2) to explore the interaction between smell/taste capacity, gastric hormones, eating behavior and body mass index (BMI). The sample comprised 239 females in EWC [64 Anorexia nervosa (AN) and 80 age-matched healthy-weight controls, and 59 obese and 36 age-matched healthy-weight controls]. Smell and taste assessments were performed through "Sniffin' Sticks" and "Taste Strips," respectively. The assessment measures included the eating disorders inventory-2, the symptom check list 90-revised, and The Dutch Eating Behavior Questionnaire, as well as peptides from the gastrointestinal tract [Ghrelin, peptide YY, cholecystokinin]. Smell capacity was differentially associated across EWC groups. Smell was clearly impaired in obese participants and increased in AN (hyposmia in Obesity was 54.3 and 6.4 % in AN), but taste capacity did not vary across EWC. Ghrelin levels were significantly decreased in obese subjects and were related to smell impairment. EWC individuals showed a distinct smell profile and circulating ghrelin levels compared to controls. Smell capacity and ghrelin may act as moderators of emotional eating and BMI.

Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase.

PURPOSE: To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase. METHODS: This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. RESULTS: After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL), neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng/mL), or mean ± SD creatinine (1.06±0.24 mg/dL vs 1.25±0.37 mg/dL at 48 hours). RV dilatation decreased from 4.23±0.7 mm to 3.45±0.6 mm and pulmonary artery pressure from 58±18 mmHg to 42±19 mmHg at 48 hours. CONCLUSION: Preoperative administration of levosimendan has shown a protective role against cardiac, renal, and neurological damage in patients with a high risk of multiple organ dysfunctions undergoing cardiac surgery.

Effects of exercise on inflammation in cardiac rehabilitation.

BACKGROUND: Programs of weight loss and a healthy diet are recommended for patients with cardiovascular risk but the effectiveness of these programs in decreasing cardiovascular mortality is controversial. AIM: To examine the acute and long-term effects of a 2-month cardiac rehabilitation program on chemokines related to inflammation in subjects with cardiovascular disease. DESIGN: Prospective cohort study. METHODS: Twenty-six patients with cardiovascular disease enrolled in a cardiac rehabilitation program based on nutritional and exercise interventions were studied. Lifestyle and clinical, metabolic and inflammatory variables were analysed. RESULTS: 88.5% were men and the mean age was 54.9 ± 7.8 years. At the end of the cardiac rehabilitation program the levels of carbohydrate and lipid metabolism were lower, except for high density lipoprotein cholesterol which was higher. The levels of uric acid, interleukin-6, interleukin-1Beta, adiponectin and leptin remained stable. Interleukin-6 correlated positively with levels of C-reactive protein and negatively with blood glucose. Interleukin-1Beta correlated positively with C-reactive protein levels and negatively with blood pressure figures. Significant correlations were seen between the changes in levels of interleukin-6 and interleukin-1Beta and changes in metabolic equivalents, and in C-reactive protein levels before and after the cardiac rehabilitation program. No significant correlations were observed with weight, waist circumference or fat mass. CONCLUSIONS: A cardiac rehabilitation program decreased anthropometric variables and blood pressure figures, and improved lipid metabolism and ergometry data. However, no changes regarding the inflammatory state were observed.

Introducción: a los pacientes con riesgo cardiovascular se les recomiendan programas de pérdida de peso y dieta saludable, pero la eficacia de estos programas a la hora de reducir la mortalidad es controvertida. Objetivo: examinar los efectos agudos y a largo plazo de un programa de rehabilitación cardíaca de dos meses de duración sobre las quemocinas relacionadas con la inflamación en pacientes con enfermedad cardiovascular. Diseño: estudio de cohortes prospectivo. Métodos: se estudiaron 26 pacientes con enfermedad cardiovascular inscritos en un programa de rehabilitación cardíaca basado en intervenciones nutricionales y de ejercicio. Se analizaron el estilo de vida y variables clínicas, metabólicas e inflamatorias. Resultados: 88,5% eran hombres y la edad media fue de 54,9 ± 7,8 años. Al final del programa de rehabilitación cardíaca las variables del perfil glucémico y lipídico descendieron, excepto el colesterol de lipoproteínas de alta densidad, que aumentó. Ácido úrico, interleucina-6, interleucina-1 beta, adiponectina y leptina se mantuvieron estables. Interleucina-6 correlacionó positivamente con proteína C reactiva y negativamente con glucosa en sangre. Interleucina-1 beta correlacionó positivamente con proteína C-reactiva y negativamente con las cifras de presión arterial. Encontramos correlaciones significativas entre los cambios en interleucina-6 e interleucina- 1 beta y los cambios en los equivalentes metabólicos y proteína C-reactiva, antes y después del programa de rehabilitación cardíaca. No se observaron correlaciones significativas con peso, circunferencia de cintura o masa grasa. Conclusiones: la rehabilitación cardiaca mejora las variables antropométricas, las cifras de presión arterial, así como el perfil de lípidos y los resultados de la ergometría. Sin embargo, no se observaron cambios con respecto al estado inflamatorio.

Differences in the Osteogenic Differentiation Capacity of Omental Adipose-Derived Stem Cells in Obese Patients With and Without Metabolic Syndrome.

Multiple studies have suggested that the reduced differentiation capacity of multipotent adipose tissue-derived mesenchymal stem cells (ASCs) in obese subjects could compromise their use in cell therapy. Our aim was to assess the osteogenic potential of omental ASCs and to examine the status of the isolated CD34(negative)-enriched fraction of omental-derived ASCs from subjects with different metabolic profiles. Omental ASCs from normal-weight subjects and subjects with or without metabolic syndrome were isolated, and the osteogenic potential of omental ASCs was evaluated. Additionally, osteogenic and clonogenic potential, proliferation rate, mRNA expression levels of proteins involved in redox balance, and fibrotic proteins were examined in the CD34(negative)-enriched fraction of omental-derived ASCs. Both the omental ASCs and the CD34(negative)-enriched fraction of omental ASCs from subjects without metabolic syndrome have a greater osteogenic potential than those from subjects with metabolic syndrome. The alkaline phosphatase and osteonectin mRNA were negatively correlated with nicotinamide adenine dinucleotide phosphate oxidase-2 mRNA and the mRNA expression levels of the fibrotic proteins correlated positively with nicotinamide adenine dinucleotide phosphate oxidase-5 mRNA and the homeostasis model assessment. Although the population doubling time was significantly higher in subjects with a body mass index of 25 kg/m(2) or greater, only the CD34(negative)-enriched omental ASC fraction in the subjects with metabolic syndrome had a higher population doubling time than the normal-weight subjects. The osteogenic, clonogenic, fibrotic potential, and proliferation rate observed in vitro suggest that omental ASCs from subjects without metabolic syndrome are more suitable for therapeutic osteogenic applications than those from subjects with metabolic syndrome.