RESUMO
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.
Assuntos
Derivação Gástrica , Obesidade Mórbida , Humanos , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Carvedilol , Obesidade/cirurgia , ComorbidadeRESUMO
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.
Assuntos
Resistência das Vias Respiratórias , Doença Pulmonar Obstrutiva Crônica , Dispneia , Feminino , Volume Expiratório Forçado , Humanos , Pulmão , Obesidade , Oscilometria , EspirometriaRESUMO
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.
Assuntos
Quimiometria , Espectrometria de Massas em Tandem , Carvedilol , Cromatografia Líquida/métodos , Humanos , Lidocaína , Extração Líquido-Líquido/métodos , Reprodutibilidade dos Testes , Estereoisomerismo , Espectrometria de Massas em Tandem/métodosRESUMO
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.
Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Obesidade Mórbida , Índice de Massa Corporal , Feminino , Humanos , Obesidade/cirurgia , Obesidade Mórbida/cirurgia , Sistema Estomatognático/cirurgiaRESUMO
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.
RESUMO
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.
Assuntos
Glicemia , MicroRNAs , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Índice de Massa Corporal , Feminino , Humanos , Lipídeos , Masculino , MicroRNAs/genética , Obesidade/genética , Sobrepeso/genética , Gordura Subcutânea , TriglicerídeosRESUMO
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.
Assuntos
Cirurgia Bariátrica , Transtornos de Deglutição , Obesidade Mórbida , Adulto , Deglutição , Transtornos de Deglutição/etiologia , Feminino , Fluoroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/cirurgia , Obesidade Mórbida/cirurgia , Adulto JovemRESUMO
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.
Assuntos
Derivação Gástrica/reabilitação , Estado Nutricional/genética , Obesidade/cirurgia , Fenótipo , Adulto , Índice de Massa Corporal , Feminino , Ácido Fólico/sangue , Seguimentos , Humanos , Ferro/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Distúrbios Nutricionais/sangue , Distúrbios Nutricionais/etiologia , Obesidade/complicações , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento , Vitamina B 12/sangue , Redução de PesoRESUMO
RESUMO Este estudo objetiva identificar informações a serem utilizadas para analisar o desempenho do acesso à atenção secundária à saúde. Foram analisados os acessos à especialidade de cirurgia digestiva do Hospital Estadual de Ribeirão Preto (HERP) e do Hospital Estadual de Américo Brasiliense (HEAB). Foram entrevistados 31 atores, em 16 organizações de saúde, com o objetivo de identificar indicadores de desempenho. Os indicadores identificados para ambos foram: 'distribuição de vagas por município', 'situação após a primeira consulta' e 'Pedidos de Interconsulta (PI)'. No acesso ao HERP, acrescentou-se o 'tempo para triagem'. Os dados para análise foram extraídos do Sistema de Apoio a Regulação Assistencial (Sara), utilizado somente no acesso ao HERP; e o sistema do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (módulo Athos), utilizado em ambos. Essas informações podem ser úteis para caracterizar os processos, compará-los e auxiliar na identificação de oportunidades de melhoria, tornando-os mais transparentes aos envolvidos. O acesso eficiente permite o uso racional de recursos e a ampliação do acesso dos pacientes aos serviços, uma vez que possibilita redução de desperdício, ociosidade e tempo de espera.
ABSTRACT This study aims to identify information to be used in order to analyze the performance of access to secondary health care. The accesses to the specialty of digestive surgery of the Ribeirão Preto State Hospital (HERP) and the Américo Brasiliense State Hospital (HEAB) were analyzed. Thirty-one actors, in 16 health organizations, were interviewed, with the purpose of identifying performance indicators. The indicators identified for both were: 'distribution of vacancies by municipality', 'situation after the first consultation' and 'requests for consultation (PI)'. In access to HERP, the 'time for screening' was added. The data for analysis were extracted from the Assistance Regulation Support System (Sara), used only to access the HERP; and the system of the Clinical Hospital of Ribeirão Preto Medical School (Athos module), used in both. This information can be useful for characterizing processes, comparing them and assist in the identification of improvement opportunities by making them more transparent to those involved. Efficient access allows rational use of resources and increased patient access to services, as it enables reduction of waste, idleness and waiting time.
RESUMO
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.