Rerouting cardiovascular management following gastric bypass surgery: Dose optimization of carvedilol using population-based analysis.

AIMS: A population-based pharmacokinetic (PK) modeling approach (PopPK) was used to investigate the impact of Roux-en-Y gastric bypass (RYGB) on the PK of (R)- and (S)-carvedilol. We aimed to optimize carvedilol dosing for these patients utilizing a pharmacokinetic/pharmacodynamic (PK/PD) link model. METHODS: PopPK models were developed utilizing data from 52 subjects, including nonobese, obese, and post- RYGB patients who received rac- carvedilol orally. Covariate analysis included anthropometric and laboratory data, history of RYGB surgery, CYP2D6 and CYP3A4 in vivo activity, and relative intestinal abundance of major drug- metabolizing enzymes and transporters. A direct effect inhibitory Emax pharmacodynamic model was linked to the PK model of (S)- carvedilol to simulate the changes in exercise- induced heart rate. RESULTS: A 2-compartmental model with linear elimination and parallel first-order absorptions best described (S)-carvedilol PK. RYGB led to a twofold reduction in relative oral bioavailability compared to nonoperated subjects, along with delayed absorption of both enantiomers. The intestinal ABCC2 mRNA expression increases the time to reach the maximum plasma concentration. The reduced exposure (AUC) of (S)-carvedilol post-RYGB corresponded to a 33% decrease in the predicted area under the effect curve (AUEC) for the 24-hour ß-blocker response. Simulation results suggested that a 50-mg daily dose in post-RYGB patients achieved comparable AUC and AUEC to 25-mg dose in nonoperated subjects. CONCLUSION: Integrated PK/PD modeling indicated that standard dosage regimens for nonoperated subjects do not provide equivalent ß-blocking activity in RYGB patients. This study highlights the importance of personalized dosing strategies to attain desired therapeutic outcomes in this patient cohort.

Relationship between the hsa miR 150-5p and FTO gene expression in white subcutaneous adipose tissue with overweight/obesity, lipid profile and glycemia.

The overweight population is growing in the world, and the search for obesity-associated mechanisms is important for a better understanding of this disease. Few studies with the FTO gene and miRs show how they associate to obesity and how they can impact this disease. The aim of this study was to verify the relationship between the FTO gene and the hsa-miR-150-5p expression with overweight/obesity, lipid profile, and fast blood glucose. Men and women (18 years older or above), with body mass index ≥ 18.5 kg/m2, were enrolled in the present study and the FTO gene and hsa-miR-150-5p expression, biochemical parameters of blood and anthropometric measurements were analyzed. The results highlight that the FTO gene expression is associated to obesity (p 0.029), LDL-C (p 0.02) and fasting blood glucose (p 0.02), but not with triglycerides (p 0.69), total cholesterol (p 0.21), and HDL-C (p 0.24). The hsa-miR-150-5p is not associated to obesity (p 0.84), triglycerides (p 0.57), total cholesterol (p 0.51), HDL-C (p 0.75), LDL-C (p 0.32), and fasting blood glucose (p 0.42). The FTO gene expression is related to obesity, LDL-C and blood fasting glucose, representing a good molecular marker for obesity.

Green tea supplementation upregulates uncoupling protein 3 expression in severe obese women adipose tissue but does not promote weight loss.

This study aims (i) to verify expression of the UCPs, PLIN1, PPARG2, and ADRB3 genes in the abdominal subcutaneous adipose tissue of obese women at baseline and after 8 weeks of supplementation with decaffeinated green tea extract, and (ii) to associate findings with clinical parameters. This is a longitudinal study during which 11 women with obesity grade III were submitted to supplementation with 450 mg of (-)-epigallocatechin gallate (EGCG) (intervention group); the control group consisted of 10 eutrophic women. Anthropometric parameters [weight, height, and body mass index (BMI)], resting metabolic rate (RMR, measured by indirect calorimetry), and gene expression (measured by real-time PCR, RT-qPCR) were determined before and after supplementation. After 8 weeks, clinical parameters and UCP1, PLIN1, PPARG2, and ADRB3 expression remained unaltered in the intervention group (p > .05). Genetic analysis also showed that the UCP3 gene was upregulated (p = .026), but its upregulation did not promote weight loss.

Impact of obesity and roux-en-Y gastric bypass on the pharmacokinetics of (R)- and (S)-omeprazole and intragastric pH.

This study employed physiologically-based pharmacokinetic-pharmacodynamics (PBPK/PD) modeling to predict the effect of obesity and gastric bypass surgery on the pharmacokinetics and intragastric pH following omeprazole treatment. The simulated plasma concentrations closely matched the observed data from non-obese, morbidly obese, and post-gastric bypass populations. Obesity significantly reduces CYP3A4 and CYP2C19 activities, as reflected by the metabolic ratio [omeprazole sulphone]/[omeprazole] and [5-hydroxy-omeprazole]/[omeprazole]. The morbidly obese model accounted for the down-regulation of CYP2C19 and CYP3A4 to recapitulate the observed data. Sensitivity analysis showed that intestinal CYP3A4, gastric pH, small intestine bypass, and the delay in bile release do not have a major influence on omeprazole exposure. Hepatic CYP3A4 had a significant impact on the AUC of (S)-omeprazole, while hepatic CYP2C19 affected both (R)- and (S)-omeprazole AUC. After gastric bypass surgery, the activity of CYP3A4 and CYP2C19 is restored. The PBPK model was linked to a mechanism-based PD model to assess the effect of omeprazole on intragastric pH. Following 40 mg omeprazole, the mean intragastric pH was 4.3, 4.6, and 6.6 in non-obese, obese, and post-gastric bypass populations, and the daily time with pH >4 was 14.7, 16.4, and 24 h. Our PBPK/PD approach provides a comprehensive understating of the impact of obesity and weight loss on CYP3A4 and CYP2C19 activity and omeprazole pharmacokinetics. Given that simulated intragastric pH is relatively high in post-RYGB patients, irrespective of the dose of omeprazole, additional clinical outcomes are imperative to assess the effect of proton pump inhibitor in preventing marginal ulcers in this population.

Effect of Roux-En-Y Gastric Bypass in the Pharmacokinetics of (R)-Carvedilol and (S)-Carvedilol.

Roux-en-Y gastric bypass is one of the most common surgical treatments for obesity due to the effective long-term weight loss and remission of associated comorbidities. Carvedilol, a third-generation ß-blocker, is prescribed to treat cardiovascular diseases. This drug is a weak base with low and pH-dependent solubility and dissolution and high permeability. As the changes in the gastrointestinal tract anatomy and physiology after roux-en-Y gastric bypass can potentially affect drug pharmacokinetics, this study aimed to assess the effect of roux-en-Y gastric bypass on the pharmacokinetics of carvedilol enantiomers. Nonobese (n = 15, body mass index < 25 kg/m2 ), obese (n = 19, body mass index ≥ 30), and post-roux-en-Y gastric bypass subjects submitted to surgery for at least 6 months (n = 19) were investigated. All subjects were administered a single oral dose of 25-mg racemic carvedilol, and blood was sampled for up to 24 hours. Plasma concentrations of (R)- and (S)-carvedilol were determined by liquid chromatography-tandem mass spectrometry. The maximum plasma concentration (Cmax ) and the area under the plasma concentration-time curve (AUC) of (R)-carvedilol were 2- to 3-fold higher than (S)-carvedilol in all groups. Obese subjects have shown reduced Cmax of (R)- and (S)-carvedilol without changing the AUC. Post-roux-en-Y gastric bypass subjects presented a 3.5-fold reduction in the Cmax of the active (S)-carvedilol and a 1.9 reduction in the AUC from time 0 to infinity compared to nonobese subjects. The time to reach Cmax of (S)-carvedilol increased 2.5-fold in post-roux-en-Y gastric bypass subjects compared to obese or nonobese. Although the ß-blockade response was not assessed, the reduced exposure to carvedilol in subjects post-roux-en-Y gastric bypass may be clinically relevant and require dose adjustment.

Increased airway resistance can be related to the decrease in the functional capacity in obese women.

BACKGROUND AND OBJECTIVE: Obesity can increase the airways resistance, mainly in the periphery, leading to dyspnea perception that can impair the functional capacity. This study aimed to analyze if airways resistance could be related to the walking capacity of women with morbid obesity. METHODS: Thirty-seven women with grade III obesity in preoperative bariatric surgery were evaluated using the spirometry test, impulse oscillometry system (IOS), and six-minute walk test (6MWT). Additionally, data about their daily dyspnea perception and physical activity level were collected. RESULTS: Variables of the spirometry test did not detect ventilator disorders. Compared to the predicted values, the IOS identified significant increase in airways resistance (kPa/L/s) (R5: 0.36 (0.34; 0.36) and 0.53 (0.47; 0.61); R20: 0.30 (0.28; 0.30) and 0.41 (0.35; 0.45); R5-20: 0.06 (0.06; 0.06) and 0.14 (0.10; 0.15); X5: -0.03 (-0.04; -0.01) and -0.20 (-0.27; -0.18), respectively). The distance walked in the 6MWT, 491.4±60.4m was significantly correlated to R5 (rho = -0.41, p = 0.01), R5-20 (rho = -0.52, p = 0.001), and X5 (rho = 0.54, p = 0.0006). CONCLUSION: The IOS is able to identify changes in airway resistance even before the onset of symptoms. When evaluated by IOS women with severe obesity and normal spirometry exhibited central and peripheral airways obstruction. The correlations between the IOS and six-minute walk distance suggest that increased peripheral airways resistance could be related to worsening functional capacity.

Effect of bariatric surgery on neurocognitive function after 6 months of follow-up: a pilot study.

Introduction: Background: reduced cognitive performance has been observed in patients with severe obesity. Bariatric surgery and subsequent adipose tissue loss seem to affect cognitive functioning positively; however, improvement predictors are not well established. Aim: to evaluate the cognitive performance and the nutritional status of patients with severe obesity 6-month after bariatric surgery. Methods: we assessed the neuropsychological performance of 22 patients with obesity (body mass index: ~ 42.9 kg/m²). The nutritional evaluation consisted of the routine tests performed in the baseline and postoperative periods. Lastly, we calculated the correlation between neuropsychological assessment results and blood biomarkers. Results: the patients did not present cognitive impairment in the preoperative assessment, but performed below the standard range. The patients underwent significant weight loss after 6 months from surgery (~ 22 kg), with a change in obesity class III to I. Also, the patients presented a significant improvement in attention, mental flexibility, inhibitory control, and processing speed. Additionally, we observed a significant improvement in serum folic acid (108 %), gamma-glutamyl transferase (-41 %), uric acid (-32 %), ferritin (-28 %), triglycerides (-19 %), and high-density lipoprotein (9 %). Lastly, we found a moderate positive correlation between processing speed and body weight (r = 0.46), gamma-glutamyl transferase (r = 0.54), and total protein and mental flexibility (r = 0.75). Conclusion: bariatric surgery promoted significant weight loss and improved attention, mental flexibility, processing speed, and several nutritional biomarkers. Nevertheless, the surgery had limited effects on other cognitive functions such as short- and long-term memory and language.

Introducción: Introducción: se ha observado una disminución del rendimiento cognitivo en los pacientes con obesidad grave. La cirugía bariátrica y la pérdida de tejido adiposo parecen mejorar el funcionamiento cognitivo; sin embargo, los predictores de mejora no están bien establecidos. Objetivos: evaluar el rendimiento cognitivo y el estado nutricional de pacientes con obesidad severa después de 6 meses de una cirugía bariátrica. Métodos: evaluamos el desempeño neuropsicológico de 22 pacientes con un índice de masa corporal ~ 42,9 kg/m². Se analizaron las pruebas de rutina realizadas al inicio y después de la cirugía. Calculamos la correlación con la evaluación neuropsicológica y los biomarcadores sanguíneos. Resultados: los pacientes no mostraron deterioro cognitivo en la evaluación preoperatoria, pero sí un rendimiento por debajo del estándar. Los pacientes mostraron una pérdida de peso significativa 6 meses después de la cirugía (~ 22 kg), con un cambio de la clasificación de obesidad de III a I. Además, los pacientes mostraron una mejora significativa de la atención, la flexibilidad mental, el control inhibitorio y la velocidad de procesamiento. Además, observamos una mejora significativa del ácido fólico sérico (108 %), la gamma-glutamil-transferasa (-41 %), el ácido úrico (-32 %), la ferritina (-28 %), los triglicéridos (-19 %) y las lipoproteínas de alta densidad (9 %). Finalmente, encontramos una correlación positiva moderada entre la velocidad de procesamiento y el peso corporal (r = 0,46) y la gamma-glutamil-transferasa (r = 0,54), y entre la proteína total y la flexibilidad mental (r = 0,75). Conclusiones: la cirugía bariátrica promovió una pérdida de peso significativa y mejoró la atención, la flexibilidad mental, la velocidad de procesamiento y varios biomarcadores nutricionales. Sin embargo, tuvo efectos limitados sobre otras funciones cognitivas, como la memoria y el lenguaje a corto y largo plazo.

Evaluation of Stomatognathic System Parameters After Bariatric Surgery.

PURPOSE: The present study aimed to evaluate electromyographic activity, bite strength, and masticatory muscle thickness in women without obesity and with severe obesity elected for bariatric surgery. Also, patients with obesity underwent bariatric surgery and were re-evaluated 3 and 6 months after surgery to analyze the influence of bariatric surgery outcomes on the stomatognathic system, a functional anatomical system comprising teeth, jaw, and associated soft tissues. MATERIAL AND METHODS: Thirty-seven women were enrolled in the study. Twenty-one women with class II and III obesity according to the body mass index (BMI) and eligible for bariatric surgery composed the obesity pre-surgery group (Ob). Sixteen women with a normal weight according to BMI composed the non-obesity group (NOb). Afterward, the patients from the Ob group were followed up for 3 and 6 months after undergoing Roux-en-Y gastric bypass. Anthropometry, body composition, and parameters of the stomatognathic system were evaluated. RESULTS: The stomatognathic system of the Ob group had less muscle activity and bite strength, but the thickness of masseter and temporal muscles was larger than the NOb group. We also observed a significant change in the muscular activity and bit strength of the stomatognathic system post-bariatric surgery. CONCLUSION: Evaluating the stomatognathic system indicated that women with clinically severe obesity have less masticatory efficiency than non-obese. Also, we found a positive influence of bariatric surgery in masticatory activity after 3 and 6 months. Thus, monitoring the parameters of the stomatognathic system could be important in the indication and outcomes of bariatric surgery.

Chemometric optimization of salting-out assisted liquid-liquid extraction (SALLE) combined with LC-MS/MS for the analysis of carvedilol enantiomers in human plasma: Application to clinical pharmacokinetics.

Carvedilol is a commonly used antihypertensive whose oral absorption is limited by low solubility and significant first-pass metabolism. This work aimed to apply chemometrics for the optimization of a salting-out assisted liquid-liquid extraction (SALLE) combined with LC-MS/MS to analyze carvedilol enantiomers in plasma samples. Method development and validation were driven for application in pharmacokinetic studies. Parameters that influence the efficiency of SALLE were evaluated using a fractional factorial 24-1 design with 4 factors and a central composite design was used to evaluate the optimal extraction condition. Carvedilol enantiomers and the internal standard lidocaine were separated on an Astec® Chirobiotic® V column and a mixture of methanol:ethanol (90:10, v/v) with 0.02% diethylamine and 0.18% acetic acid as mobile phase. The positive ion mode on electrospray ionization was used to monitor the transitions of m/z 407 > 100 and 235 > 86 for carvedilol enantiomers and lidocaine, respectively. Acetonitrile and ammonium acetate solution were selected for sample preparation by SALLE. Surface graphs and the desirability test were used to define the optimized SALLE conditions which resulted in 93% recovery for both carvedilol enantiomers. The method was linear in the range of 0.5 to 100 ng/mL in plasma, with a lower limit of quantification of 0.5 ng/mL. Within-run and between-run precision (as the relative standard deviation) were all < 9.74% and accuracy (as relative error) did not exceed ± 10.30%. Residual effect and matrix effect were not observed. Carvedilol enantiomers were stable in plasma under the storage, preparation, and analysis conditions. The validated method was successfully applied to analyze carvedilol in plasma samples from patients previously submitted to a Roux-en-Y gastric bypass surgery treated with a single oral dose of 25 mg racemic-carvedilol. Higher plasma concentrations were observed for (R)-(+)-carvedilol when compared to (S)-(-)-carvedilol in two patients post-bariatric surgery.

Differential Expression of MMP2 and TIMP2 in Peripheral Blood Mononuclear Cells After Roux-en-Y Gastric Bypass.

Matrix metalloproteinases (MMP) and their endogenous inhibitor, the tissue inhibitor of metalloproteinases (TIMP), are expressed in many different cell types and play an important role in physiologic and pathological degradation of extracellular matrix (ECM). Starting from these observations and considering the activation state of peripheral blood mononuclear cells (PBMCs) in obesity, we investigated the gene expression of metalloproteinases before and after Roux-en-Y gastric bypass (RYBG). The study was performed in the Ribeirão Preto Medical School University Hospital. Seventy-three women were divided into a study group (SG), composed of 53 individuals with severe obesity before and after 6 months of RYGB, and a control group (CG), composed of 20 normal-weight individuals. Anthropometric and body composition data were collected, and peripheral blood for ribonucleic acid (RNA) extraction. The biological samples were submitted to a quantitative real-time polymerase chain reaction to evaluate the expression of MMP2 and TIMP2 genes. Alterations in weight loss, body mass index (BMI), and fat mass (FM) were observed after 6 months of RYGB (p < 0.05). A reduction of gene expression of TIMP2 was observed after 6 months of RYGB, contributing positively to the weight loss (R 2 = 0.33 p = 0.04). The enrichment analyses highlighted the interaction between TIMP2 and MMP2 genes and the molecular pathways involving the ECM remodeling in the obesity condition. RYGB contributes significantly to weight loss, improved BMI, reduced FM, and reduced TIMP2 expression in PBMCs, which might contribute to the ECM remodeling in the obesity and could be useful as a circulating biomarker.

Swallowing in Obese Individuals before and after Bariatric Surgery.

PURPOSE: To evaluate the oral and pharyngeal phases of swallowing in obese patients before and after bariatric surgery. MATERIAL AND METHOD: Swallowing was evaluated by videofluoroscopy before and after 80 to 123 days from bariatric surgery in 19 individuals with obesity (15 women), aged 25-60 years. The body mass index (BMI) before surgery was from 40.1 to 57.0 kg/m2. The surgical treatment was performed with laparoscopic Roux-en-Y gastric by-pass (RYGB). After surgery, the BMI ranged from 31.7 to 48.4 kg/m2. The control group had 19 healthy volunteers (15 women), aged 22-56 years and BMI from 19.4 to 29.7 kg/m2. Swallowing was evaluated with swallows of 5 mL of liquid and paste boluses in triplicate, and a solid bolus in duplicate. RESULTS: With swallowing of liquid bolus, individuals with obesity had, before and after surgery, an increased frequency of premature posterior spillage. Before the surgery, the obese subjects had longer pharyngeal clearance of liquid compared with the control group and with individuals after the surgery. After the surgery, obese individuals had longer duration of the hyoid movement with liquid and paste boluses, compared with before surgery. Also, there was a reduction of the interval between the bolus entering the phaynx and the onset of upward hyoid excursion. CONCLUSION: Non-operated obese patients had a longer pharyngeal clearance for liquid bolus compared with healthy controls. After bariatric surgery, there was an increase in hyoid movement duration.

Transabdominal preperitoneal (TAPP) versus open Lichtenstein hernia repair. Comparison of the systemic inflammatory response and the postoperative pain1.

PURPOSE: To compare open Lichtenstein repair and laparoscopic transabdominal preperitoneal (TAPP) repair to treat primary unilateral hernia, regarding systemic inflammatory response, postoperative pain, and complications. METHODS: A non-randomized prospective cohort study, with the preoperative and postoperative (24 hours) collection of blood samples for C reactive protein (CRP), interleukin 6 (IL-6), leukocyte and neutrophil analysis. Visual Analog Scale (VAS) was used to quantify the level of pain, and the operative time was correlated with the inflammatory response. VAS and CRP were also obtained on the 8th postoperative day. RESULTS: Groups were homogeneous regarding preoperative characteristics. There were no differences between groups in 24h values of CRP, IL-6, leukocytes, neutrophils or VAS. Similarly, CRP and VAS did not differ between groups on the 8th postoperative day. However, the operative time for laparoscopic hernia repair was longer than the time for the open procedure. There was a weak correlation (r coefficient 0.31) between the duration of the surgical procedure and the VAS score at the eighth day. CONCLUSIONS: There were no statistically significant differences in the inflammatory response, pain scores, or complications between groups. We conclude that there is no advantage performing a primary unilateral hernia repair by laparoscopy.

IS THERE ANY CHANGE IN PHENOTYPIC CHARACTERISTICS COMPARING 5 TO 10 YEARS OF FOLLOW-UP IN OBESE PATIENTS UNDERGOING ROUX-EN-Y GASTRIC BYPASS?

BACKGROUND: : Bariatric surgery promotes significant weight loss and improvement of associated comorbidities; however, nutrients deficiencies and weight regain may occur in the middle-late postoperative period. AIM: To investigate nutritional status in 10 years follow-up. METHODS: : Longitudinal retrospective study in which anthropometric, biochemical indicators and nutritional intake were assessed before and after one, two, three, four, five and ten years of Roux-en Y gastric bypass through analysis of medical records. RESULTS: : After ten years there was a reduction of 29.2% of initial weight; however, 87.1% of patients had significant weight regain. Moreover, there was an increase of incidence of iron (9.2% to 18.5%), vitamin B12 (4.2% to 11.1%) and magnesium deficiency (14.1% to 14.8%). Folic acid concentrations increased and the percentage of individuals with glucose (40.4% to 3.7%), triglycerides (38% to 7.4%), HDL cholesterol (31 % to 7.4%) and uric acid (70.5% to 11.1%) abnormalities reduced. Also, there is a reduction of food intake at first year postoperative. After 10 years, there was an increase in energy, protein and lipid intake, also a reduction in folid acid intake. CONCLUSIONS: : Roux-en Y gastric bypass is an effective procedure to promote weight loss and improve comorbidities associated with obesity. However, comparison between postoperative period of five and 10 years showed a high prevalence of minerals deficiency and a significant weight regain, evidencing the need for nutritional follow-up in the postoperative period.

DEPRESSION, ANXIETY, AND BINGE EATING BEFORE AND AFTER BARIATRIC SURGERY: PROBLEMS THAT REMAIN.

BACKGROUND: As the number of surgeries increases and the elapsed time of the realization increases as well, the postoperative evaluations would become increasingly necessary. AIM: To assess the psychological profile before and after surgery. METHODS: Were evaluated 281 patients from the public service of bariatric surgery. In this study, 109 patients completed the evaluations before surgery (T0) and up to 23 months after surgery (T1); 128 completed the evaluations in T0 and between 24 months and 59 months after surgery (T2); and 44 completed the evaluations in T0 and 60 months after surgery (T3). A semi-structured interview, the Beck Depression Inventory (BDI), Beck Anxiety (BAI), and the Binge Eating Scale (BES) were used. RESULTS: There was a higher prevalence of female (83%), patients with less than 12 years of education (83%), and patients who have a partner (64%). Analyzing all times of evaluation, regarding anxiety, depression, and binge eating, there was a reduction in all symptoms in T1, pointing to significant improvements in the first 23 months after surgery. Already, in T2 and T3, there was an increase in all indicators of anxiety, depression, and binge eating pointing to the transient impact of weight loss or bariatric surgery on these symptoms. CONCLUSIONS: This study shows the importance of the continuous psychological evaluation and needs for the appropriate interventions for these patients who have undergone bariatric surgery, even after weight loss.

Nutritional Status of Children from Women with Previously Bariatric Surgery.

BACKGROUND: Number of pregnancies has been increasing in women of childbearing age after the gastric bypass. OBJECTIVE: The objective of this study was to evaluate the nutritional status of children of women submitted to gastric bypass. METHODS: We evaluated anthropometric, breastfeeding and biochemical profile, body composition, and dietary intake indicators of children of both sexes who were born alive after the surgery. For statistical analysis, were performed Shapiro-Wilk and ANOVA test (p < 0.05). RESULTS: The sample consisted of 13 children (61.6% female, mean age of 46 ± 22.3 months, BMI of 18.9 ± 3.3 kg/m2). The classification of BMI index by age showed that 46.1% of the children were normal weight and 30.8% obese. We observed a large percentage of children with deficiency of iron and vitamin A. 7.6 and 30.7% of children presented carbohydrate and lipid, respectively, lower than the recommendation. Fiber intake was inadequate in all children, calcium in 61.5%, vitamin A in 30.7%, and folate in 76.9% of them. Also, 84.6% presented sodium intake higher than the recommendations. The blood glucose levels were lower in children with maternal breastfeeding (65.5 ± 2.1 mg/dL, p < 0.05); furthermore, children breastfed with artificial and breast milk presented lower fat mass (3.8 ± 1.9 kg; p < 0.05). CONCLUSION: Children from women with previously gastric bypass presented low birth weight; however, they are currently underweight or overweight and present important deficiency of iron and vitamin A and inadequate alimentary intake mainly of sodium and fibers. Breastfeeding may play a protective role in the development of obesity in these children.

Influence of expression of UCP3, PLIN1 and PPARG2 on the oxidation of substrates after hypocaloric dietary intervention.

BACKGROUND & AIMS: In addition to environmental and psychosocial factors, it is known that genetic factors can also influence the regulation of energy metabolism, body composition and determination of excess weight. The objective of this study was to evaluate the influence of UCP3, PLIN1 and PPARG2 genes on the substrates oxidation in women with grade III obesity after hypocaloric dietary intervention. SUBJECTS/METHODS: This is a longitudinal study with 21 women, divided into two groups: Intervention Group (G1): 11 obese women (Body Mass Index (BMI) ≥40 kg/m2), and Control Group (G2): 10 eutrophic women (BMI between 18.5 kg/m2 and 24.9 kg/m2). Weight (kg), height (m), BMI (kg/m2), substrate oxidation (by Indirect Calorimetry) and abdominal subcutaneous adipose tissue were collected before and after the intervention. For the dietary intervention, the patients were hospitalized for 6 weeks receiving 1200 kcal/day. RESULTS: There was a significant weight loss (8.4 ± 4.3 kg - 5.2 ± 1.8%) and reduction of UCP3 expression after hypocaloric dietary intervention. There was a positive correlation between carbohydrate oxidation and UCP3 (r = 0.609; p = 0.04), PLIN1 (r = 0.882; p = 0.00) and PPARG2 (r = 0.791; p = 0.00) expression before dietary intervention and with UCP3 (r = 0.682; p = 0.02) and PLIN1 (r = 0.745; p = 0.00) genes after 6 weeks of intervention. There was a negative correlation between lipid oxidation and PLIN1 (r = -0.755; p = 0.00) and PPARG2 (r = 0.664; p = 0.02) expression before dietary intervention and negative correlation with PLIN1 (r = 0.730; p = 0.02) expression after 6 weeks of hypocaloric diet. CONCLUSION: Hypocaloric diet reduces UCP3 expression in individuals with obesity and the UCP3, PLIN1 and PPARG2 expression correlate positively with carbohydrate oxidation and negatively with lipid oxidation.

Changes in Global Transcriptional Profiling of Women Following Obesity Surgery Bypass.

BACKGROUND: Differential gene expression in peripheral blood mononuclear cells (PBMCs) after Roux-en-Y gastric bypass (RYGB) is poorly characterized. Markers of these processes may provide a deeper understanding of the mechanisms that underlie these events. The main goal of this study was to identify changes in PBMC gene expression in women with obesity before and 6 months after RYGB-induced weight loss. METHODS: The ribonucleic acid (RNA) of PBMCs from 13 obese women was analyzed before and 6 months after RYGB; the RNA of PBMCs from nine healthy women served as control. The gene expression levels were determined by microarray analysis. Significant differences in gene expression were validated by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: Microarray analysis for comparison of the pre- and postoperative periods showed that 1366 genes were differentially expressed genes (DEGs). The main pathways were related to gene transcription; lipid, energy, and glycide metabolism; inflammatory and immunological response; cell differentiation; oxidative stress regulation; response to endogenous and exogenous stimuli; substrate oxidation; mTOR signaling pathway; interferon signaling; mitogen-activated protein kinases (MAPK), cAMP response element binding protein (CREB1), heat shock factor 1 (HSF1), and sterol regulatory element binding protein 1c (SREBP-1c) gene expression; adipocyte differentiation; and methylation. CONCLUSIONS: Six months after bariatric surgery and significant weight loss, many molecular pathways involved in obesity and metabolic diseases change. These findings are an important tool to identify potential targets for therapeutic intervention and clinical practice of nutritional genomics in obesity.

Development of a lethal model of peritonitis for assessment of laparoscopic and laparotomic treatments in rats.

PURPOSE: Development of a lethal model of peritonitis to assess the results of treating that peritonitis using videolaparoscopy and laparotomy. METHODS: We developed a model of peritonitis in rats using cecal ligation (CLP) against a 2-mm diameter rigid mold and puncture. Two experiments were performed: determination of seven-day lethality; and analysis of white cell counts, blood cultures and cytokines (Interleukin-1 beta, Tumor Necrosis Factor-alpha and IL-6). The animals were divided into four groups: I--Sham surgery; II--CLP; III--CLP + Videolaparoscopy; and IV--CLP + Laparotomy . RESULTS: Seven-day lethality was 0% in group I, 80% in the group II (p<0.05), 60% in group III , and 20 % in group IV. There was a significant reduction in leukocyte counts and higher levels of serum IL-1 beta, TNF-alpha and IL-6 in the group II compared to controls. The percentages of positive blood cultures were higher after videolaparoscopic compared to laparotomic treatment. CONCLUSION: The experimental model provoked a lethal form of peritonitis and that videolaparoscopic treatment had more bacteraemia than laparotomy.

Pregnancy After Roux en Y Gastric Bypass: Nutritional and Biochemical Aspects.

INTRODUCTION: Although pregnancy after bariatric surgery is related to risk reduction, nutritional complications may occur. This study aimed to evaluate nutritional and biochemical indicators of women who became pregnant after Roux en Y gastric bypass (RYGB). MATERIALS AND METHODS: We carried out a retrospective study with women who became pregnant after RYGB. We evaluated anthropometric, biochemical, and dietary intake indicators in the preoperative period and before, during, and after pregnancy by analysis of medical records. Shapiro-Wilk test and ANOVA for repeated measures were performed (p < 0.05). RESULTS: The study included 25 patients (35.7 ± 3.8 years), who became pregnant 31.3 ± 21.7 months after RYGB. Weight loss until the beginning of pregnancy was 32.4%, and the gestational weight gain was 3.8 ± 12 kg. There was a higher frequency of patients with hypertension in the preoperative time when compared to that during the pregnancy period. Total cholesterol (180.9 ± 24.8 versus 148.5 ± 30.4 mg/dL), LDL-cholesterol (103.5 ± 19.2 versus 85.8 ± 23.1 mg/dL), HDL-cholesterol (56.4 ± 8 versus 46.9 ± 8.7 mg/dL), and latent iron-binding capacity (337.6 ± 95.8 versus 277.8 ± 65 µg/dL) were higher during the pregnancy compared to that before the pregnancy, while hemoglobin values (11.2 ± 1 versus 12.3 ± 1.2 g/dL) and sodium (138.8 ± 2.9 versus 141 ± 3 mmol/L) were lower. No differences of food intake were found among times. There is no difference on gestational weight gain between women who became pregnant before or after the first year. CONCLUSION: During pregnancy, there was an expected weight gain and maintenance of the lipid profile within the normal range; however, there was a reduction of hemoglobin levels. These findings show the need for individualized follow-up with adequate nutritional intervention in the event of deficiencies.

Comparison of gene expression profile between blood cells and white adipose tissue of patients with obesity

INTRODUCTION: Gene expression analyses from peripheral blood mononuclear cells (PBMC) and white adipose tissue are conflicting. It seems that results from single tissue are not enough to explain how changes affect humans as a complex biological system. OBJECTIVE: The aim of this study was to compare, from obesity subjects, PBMC and white adipose tissue gene expression that regulates adipogenesis (perilipin 1 [PLIN1], adrenoreceptor beta 3 [ADRB3] and peroxisome proliferator-activated receptor [PPARG2]) and the energy metabolism (uncoupling protein UCP1, UCP2 and UCP3) process. METHODS: This study enrolled 35 obese patients, with a body mass index (BMI) > 40 kg/m2 (obesity group [OG]), and ten eutrophic health subjects, 18 > BMI > 24.9 kg/m2 (control group [CG]). Anthropometric and body composition data were assessed at recruitment using standardized protocols. Samples of peripheral blood and subcutaneous adipose tissue (biopsy) were collected to analyze gene expression by RT-qPCR technique. For statistical analysis, we used the Shapiro-Wilk test and Wilcoxon tests by the SPSS software version 20.0; a p < 0.05 significance level was adopted. RESULTS: There were significant differences of PLIN1, ADRB3, PPARG2 and UCP3 expression between blood against adipose tissue samples, showing that these genes are upregulated in adipose tissue. UCP2 expression was upregulated in PBMC. CONCLUSION: The PLIN1, ADRB3, PPARG2 and UCP3 genes were preferentially expressed in adipose tissue. However, UCP2 was upregulated in PBMC, suggesting that this gene may be assessed in a peripheral blood cell, which is easily accessible, safe and practical.