Use of N-acetylcysteine plus simethicone to improve mucosal visibility in upper digestive endoscopy via systematic alphanumeric-coded endoscopy: a randomized, double-blind controlled trial.

Background: The use of antifoaming and mucolytic agents prior to upper gastrointestinal (GI) endoscopy and a thorough systematic review are essential to optimize lesion detection. This study evaluated the effect of simethicone and N-acetylcysteine on the adequate mucosal visibility (AMV) of the upper GI tract by an innovative systematic method. Methods: This randomized, double-blind controlled trial included consecutive patients who underwent diagnostic upper GI endoscopy for screening for early neoplasms between August 2019 and December 2019. The upper GI tract was systematically assessed by systematic alphanumeric-coded endoscopy. Patients were divided into 4 groups: 1) water; 2) only simethicone; 3) N-acetylcysteine + simethicone; and 4) only N-acetylcysteine. The following parameters were assessed in each group: age, sex, body mass index, level of adequate mucosal visibility, and side-effects. Results: A total of 4564 images from upper GI areas were obtained for evaluation. The mean AMV in the 4 groups was 93.98±7.36%. The N-acetylcysteine + simethicone group had a higher cleaning percentage compared with the other groups (P=0.001). There was no significant difference among the remaining groups, but several areas had better cleaning when a mucolytic or antifoam alone was used. No side-effects were found in any group. Conclusion: The combination of N-acetylcysteine plus simethicone optimizes the visibility of the mucosa of the upper GI tract, which could potentially increase diagnostic yield.

Sacubitril/valsartan inhibits obesity-associated diastolic dysfunction through suppression of ventricular-vascular stiffness.

OBJECTIVE: Cardiac diastolic dysfunction (DD) and arterial stiffness are early manifestations of obesity-associated prediabetes, and both serve as risk factors for the development of heart failure with preserved ejection fraction (HFpEF). Since the incidence of DD and arterial stiffness are increasing worldwide due to exponential growth in obesity, an effective treatment is urgently needed to blunt their development and progression. Here we investigated whether the combination of an inhibitor of neprilysin (sacubitril), a natriuretic peptide-degrading enzyme, and an angiotensin II type 1 receptor blocker (valsartan), suppresses DD and arterial stiffness in an animal model of prediabetes more effectively than valsartan monotherapy. METHODS: Sixteen-week-old male Zucker Obese rats (ZO; n = 64) were assigned randomly to 4 different groups: Group 1: saline control (ZOC); Group 2: sacubitril/valsartan (sac/val; 68 mg•kg-1•day-1; ZOSV); Group 3: valsartan (31 mg•kg-1•day-1; ZOV) and Group 4: hydralazine, an anti-hypertensive drug (30 mg•kg-1•day-1; ZOH). Six Zucker Lean (ZL) rats that received saline only (Group 5) served as lean controls (ZLC). Drugs were administered daily for 10 weeks by oral gavage. RESULTS: Sac/val improved echocardiographic parameters of impaired left ventricular (LV) stiffness in untreated ZO rats, without altering the amount of food consumed or body weight gained. In addition to improving DD, sac/val decreased aortic stiffness and reversed impairment in nitric oxide-induced vascular relaxation in ZO rats. However, sac/val had no impact on LV hypertrophy. Notably, sac/val was more effective than val in ameliorating DD. Although, hydralazine was as effective as sac/val in improving these parameters, it adversely affected LV mass index. Further, cytokine array revealed distinct effects of sac/val, including marked suppression of Notch-1 by both valsartan and sac/val, suggesting that cardiovascular protection afforded by both share some common mechanisms; however, sac/val, but not val, increased IL-4, which is increasingly recognized for its cardiovascular protection, possibly contributing, in part, to more favorable effects of sac/val over val alone in improving obesity-associated DD. CONCLUSIONS: These studies suggest that sac/val is superior to val in reversing obesity-associated DD. It is an effective drug combination to blunt progression of asymptomatic DD and vascular stiffness to HFpEF development in a preclinical model of obesity-associated prediabetes.

Diabetes screen during tuberculosis contact investigations highlights opportunity for new diabetes diagnosis and reveals metabolic differences between ethnic groups.

Type 2 diabetes (T2D) is a prevalent risk factor for tuberculosis (TB), but most studies on TB-T2D have focused on TB patients, been limited to one community, and shown a variable impact of T2D on TB risk or treatment outcomes. We conducted a cross-sectional assessment of sociodemographic and metabolic factors in adult TB contacts with T2D (versus no T2D), from the Texas-Mexico border to study Hispanics, and in Cape Town to study South African Coloured ethnicities. The prevalence of T2D was 30.2% in Texas-Mexico and 17.4% in South Africa, with new diagnosis in 34.4% and 43.9%, respectively. Contacts with T2D differed between ethnicities, with higher smoking, hormonal contraceptive use and cholesterol levels in South Africa, and higher obesity in Texas-Mexico (p < 0.05). PCA analysis revealed striking differences between ethnicities in the relationships between factors defining T2D and dyslipidemias. Our findings suggest that screening for new T2D in adult TB contacts is effective to identify new T2D patients at risk for TB. Furthermore, studies aimed at predicting individual TB risk in T2D patients, should take into account the heterogeneity in dyslipidemias that are likely to modify the estimates of TB risk or adverse treatment outcomes that are generally attributed to T2D alone.

Improvement of cardiometabolic markers after fish oil intervention in young Mexican adults and the role of PPARα L162V and PPARγ2 P12A.

Polyunsaturated fatty acids (PUFA) contained in fish oil (FO) are ligands for peroxisome proliferator-activated receptors (PPAR) that may induce changes in cardiometabolic markers. Variation in PPAR genes may influence the beneficial responses linked to FO supplementation in young adults. The study aimed to analyze the effect of FO supplementation on glucose metabolism, circulating lipids and inflammation according to PPARα L162V and PPARγ2 P12A genotypes in young Mexican adults. 191 young, non-smoking subjects between 18 and 40 years were included in a one-arm study. Participants were supplemented with 2.7 g/day of EPA+DHA, during six weeks. Dietary analysis, body composition measurements and indicators for glucose metabolism, circulating lipids, and markers for inflammation were analyzed before and after intervention. An overall decrease in triglycerides (TG) and an increase in HS-ω3 index were observed in all subjects [-4.1 mg/dL, (SD:±51.7), P=.02 and 2.6%, (SD:±1.2), P<.001 respectively]. Mean fasting insulin and glycated hemoglobin (HbA1c%) were significantly decreased in all subjects [-0.547mlU/L, (SD:±10.29), P=.034 and-0.07%, (SD:±0.3), P<.001 respectively], whereas there was no change in body composition, fasting glucose, adiponectin and inflammatory markers. Subjects carrying the minor alleles of PPARα L162V and PPARγ2 P12A had higher responses in reduction of TG and fasting insulin respectively. Interestingly, doses below 2.7 g/day (1.8 g/day) were sufficient to induce a significant reduction in fasting insulin and HbA1c% from baseline (P=.019 and P<.001). The observed responses in triglycerides and fasting insulin in the Mexican population give further evidence of the importance of FO supplementation in young people as an early step towards the prevention of cardiometabolic disease.

Alterations in Activation, Cytotoxic Capacity and Trafficking Profile of Peripheral CD8 T Cells in Young Adult Binge Drinkers.

BACKGROUND: Excess of alcohol consumption is a public health problem and has documented effects on the immune system of humans and animals. Animal and in vitro studies suggest that alcohol abuse changes CD8 T cell (CD8) characteristics, however it remains unknown if the CD8 profile of binge drinkers is different in terms of activation, trafficking and cytotoxic capacity. AIM: To analyze the peripheral CD8 cytotoxic capacity, activation and trafficking phenotypic profile of Mexican young adults with regard to alcohol consumption pattern. METHODS: 55 Mexican young adults were stratified as Light (20), Intermediate (18) or Binge drinkers (17) according to their reported alcohol consumption pattern. Blood samples were obtained and hematic biometry and liver enzyme analysis were performed. Peripheral CD8 profile was established by expression of Granzyme B (GB), CD137, CD127, CD69, TLR4, PD1, CCR2, CCR4, CCR5 and CXCR4 by FACS. Data was analyzed by ANOVA, posthoc DMS and Tamhane, and principal component analysis (PCA) with varimax rotation, p<0.05. RESULTS: The Binge drinking group showed increased γGT together with increased expression of CD69 and reduced expression of TLR4, PD1, CCR2 and CXCR4 in peripheral CD8 cells. Other parameters were also specific to Binge drinkers. PCA established 3 factors associated with alcohol consumption: "Early Activation" represented by CD69 and TLR4 expression in the CD8 population; "Effector Activation" by CD69 expression in CD8 CD127(+)CD137(+) and CD8 CD25(+) CD137(+); and Trafficking by CXCR4 expression on total CD8 and CD8 GB(+)CXCR4(+), and CCR2 expression on total CD8. Binge drinking pattern showed low expression of Early Activation and Trafficking factors while Light drinking pattern exhibited high expression of Effector Activation factor. CONCLUSIONS: Alcohol consumption affects the immune phenotype of CD8 cells since binge drinking pattern was found to be associated with high CD69 and low TLR4, CXCR4 and CCR2 expression, which suggest recent activation, decreased sensitivity to LPS and lower migration capacity in response to chemokines SDF-1 and MCP-1. These results indicate that a binge-drinking pattern of alcohol consumption may induce an altered immune profile that could be related with liver damage and the increased susceptibility to infection reported to this behavior.

Validation and Standardization of the Weight Control Perceived Self-Efficacy Inventory in a Mexican College Population / Validación y estandarización del inventario auto-eficacia percibida para el control de peso en población mexicana universitaria / Validação e padronização do inventário autoeficácia percebida para o controle de peso em população mexicana universitária

Purpose: The purpose of the study was to evaluate if the Weight Control Perceived Self-efficacy Inventory (WC-PSE) is reproducible in a Mexican college population. Methods and materials: This is an observational and prolective process study. Sixty subjects from two geographical regions of Mexico were invited to answer the WC-PSE on two separate occasions. Findings: The Content Validity Index was 0.96. The mean difference in the test retest was <4 in all domains; the intra-class correlation coefficient was >0.7; Cronbach's coefficient was α=.95. The inventory was sensitive to detecting differences according to gender and degrees of body mass index. Conclusion: The WC-PSE inventory is reproducible and sensitive for application to a Mexican college population.

Objetivo: evaluar si el inventario auto-eficacia percibida para el control de peso (AP-CP) es reproducible en población universitaria. Material y métodos: estudio de proceso, observacional y prolectivo. Se invitó a 60 sujetos de dos regiones geográficas de México para responder el AP-CP en dos ocasiones por separado. Resultados: el Índice de Validez de Contenido fue de 0.96. En la prueba re-prueba, la diferencia promedio fue < 4 en todos los dominios, coeficiente de correlación intra-clase > 0.7; coeficiente α=0.95. El inventario también fue sensible para detectar diferencias de acuerdo a género y grados de IMC. Conclusión: el inventario AP-CP es reproducible y sensible para aplicarse en población mexicana universitaria.

Objetivo: Avaliar se o inventário Autoeficácia Percebida para Controle de Peso (AP-CP) pode ser reproduzido em população universitária. Material e métodos: Estudo de processo, observacional e proletivo. Sessenta sujeitos de duas regiões geográficas do México foram convidados para responder ao AP-CP em duas ocasiões separadamente. Resultados: O Índice de Validade de Conteúdo foi de 0,96%. Na prova re-prova, a diferença média foi de < 4 em todos os domínios, coeficiente de correlação intraclasse > 0,7; coeficiente α=0,95. O inventário também foi sensível para detectar diferenças de acordo com o gênero e graus de IMC. Conclusão: O inventário AP-CP pode ser reproduzido e é sensível para ser aplicado na população mexicana universitária.

Efecto del ejercicio cardiovascular en las mujeres con obesidad sobre las concentraciones de la adiponectina, leptina y factor de necrosis tumoral-alfa / Cardiovascular exercise on obese women: Effects on adiponectine, leptine, and tumour necrosis factor-alpha

Introducción: La relación de las hormonas adiponectina, leptina y factor de necrosis tumoral-alfa del tejido adiposo sobre el proceso aterogénico es uno de los modelos más prometedores en la medicina preventiva. Los numerosos ensayos realizados para identificar el efecto del ejercicio sobre estas hormonas no han sido claros en el tipo de rutina de ejercicio y esfuerzo físico calculado que contribuya al cambio de las concentraciones plasmática en mujeres con obesidad. Objetivo: Analizar el efecto del ejercicio cardiovascular controlado sobre los niveles séricos de la adiponectina, la leptina y el factor de necrosis tumoral-alfa en mujeres jóvenes con obesidad. Método: Ensayo clínico simple ciego. La intervención consistió en un programa de ejercicio cardiovascular controlado durante 10 semanas en 34 mujeres (casos n = 17; controles n = 17), con un índice de masa corporal > 27 kg/m². Se realizó análisis molecular por inmunofluorescencia. Resultados: Posterior a la intervención, las medias de los casos y controles fueron las siguientes: adiponectina 19 vs. 12.2 μ/ml (p = 0.008); leptina 20 vs. 28 μ/L (p = 0.02) y factor de necrosis tumoral-alfa 4.7 vs. 5.1 pg/ml (p = 0.05). Conclusiones: La rutina de ejercicio establecida (5 sesiones a la semana de ejercicio de 40 min cada una durante 10 semanas con una frecuencia cardiaca de reserva del 40 al 80%) mejoró las concentraciones plasmáticas de las hormonas en la dirección esperada. Este hallazgo destaca una rutina inédita de ejercicio, controlada por frecuencia cardiaca de reserva que podría contribuir a la protección cardiovascular y metabólica en mujeres jóvenes obesas.

Introduction: The relationship of hormones adiponectin, leptin and tumor necrosis factor-alpha in adipose tissue on the atherogenic process is one of the most promising models in preventive medicine. The numerous tests performed to identify the effect of exercise on these hormones have not been clear on the type of exercise routine and physical effort calculated to contribute to changing plasma concentrations in obese women. Objective: Analyze controlledcardiovascular exercise effect on serum level of adiponectin, leptin, and tumournecrosis factor-alpha in obese young women. Method: A simple blind clinical essay. The intervention covered a 10-week controlled, cardiovascular exercise program by 34 women (cases n = 17, controls n = 17) with a body mass index > 27 kg/m². Molecular analysis was performed by immune-fluorescence. Results: Following the intervention, cases and controls means were as follows: adiponectin 19.0 vs. 12.2 μ/ml (P = .008); leptin 20.0 vs. 28.0 μ/L (P = .02); and tumour necrosis factor-alpha 4.7 vs. 5.1 pg/ml (P = .05). Conclusions: The established exercise (5 sessions a week of exercise of 40 min each for 10 weeks with a heart rate reserve of 40 to 80%) improved plasma concentrations of these hormones in the expected direction. This finding highlights an unpublished amount of exercise, controlled by the reserve cardiac frequency that might contribute the cardiovascular and metabolic protection to obese women.

[Cardiovascular exercise on obese women: effects on adiponectine, leptine, and tumour necrosis factor-alpha]. / Efecto del ejercicio cardiovascular en las mujeres con obesidad sobre las concentraciones de la adiponectina, leptina y factor de necrosis tumoral-alfa.

INTRODUCTION: The relationship of hormones adiponectin, leptin and tumor necrosis factor-alpha in adipose tissue on the atherogenic process is one of the most promising models in preventive medicine. The numerous tests performed to identify the effect of exercise on these hormones have not been clear on the type of exercise routine and physical effort calculated to contribute to changing plasma concentrations in obese women. OBJECTIVE: Analyze controlledcardiovascular exercise effect on serum level of adiponectin, leptin, and tumournecrosis factor-alpha in obese young women. METHOD: A simple blind clinical essay. The intervention covered a 10-week controlled, cardiovascular exercise program by 34 women (cases n=17, controls n=17) with a body mass index>27kg/m(2). Molecular analysis was performed by immune-fluorescence. RESULTS: Following the intervention, cases and controls means were as follows: adiponectin 19.0 vs. 12.2µ/ml (P=.008); leptin 20.0 vs. 28.0µ/L (P=.02); and tumour necrosis factor-alpha 4.7 vs. 5.1pg/ml (P=.05). CONCLUSIONS: The established exercise (5 sessions a week of exercise of 40min each for 10 weeks with a heart rate reserve of 40 to 80%) improved plasma concentrations of these hormones in the expected direction. This finding highlights an unpublished amount of exercise, controlled by the reserve cardiac frequency that might contribute the cardiovascular and metabolic protection to obese women.

IL-10 and TNF-alpha polymorphisms in subjects with irritable bowel syndrome in Mexico.

BACKGROUND: there has been recent evidence of an alteration in irritable bowel syndrome (IBS) immune regulation, as well as variations in cytokine polymorphisms. AIMS: to determine the frequency of the IL-10 (-1082G/A) and TNF-alpha (-308G/A) polymorphisms in subjects with IBS in Mexico. METHODS: volunteers answered the Rome II Questionnaire and were classified as IBS (n = 45) and controls (n = 92). The IBS subjects were then categorized as IBS-D: 22.2%, IBS-C: 28.9%, and IBS-A/M: 48.9%. The polymorphism frequency among groups was compared. RESULTS: there were no differences between IBS vs. controls in the frequency of the high (8.9 vs. 18.5%), intermediate (60.0 vs. 57.6%), or low (23.9 vs. 38.9%) producer IL-10 genotypes, p = 0.315. Neither were there differences in the high (0 vs. 1.1%), intermediate (55.4 vs. 43.2%), or low (43.5 vs. 56.8%) producer TNF-alpha genotypes, p = 0.296. However the low producer of IL-10 was more frequent in IBS-D vs. IBS-C vs. IBS-A/M (63.6 vs. 7.1 vs. 33,3%) p = 0.023. CONCLUSIONS: in this group of volunteers in Mexico, the frequency of the IL-10 (-1082G/A) and TNF-alpha (-308G/A) genotypes was similar in IBS and controls. However, there was a greater frequency of the low producer of IL-10 in those subjects with IBS-D, suggesting a genetic predisposition to abnormal immune regulation due to a lower anti-inflammatory component in this subgroup.

Epidemiologic investigation of tuberculosis in a Mexican population from Chihuahua State, Mexico: a pilot study.

Tuberculosis (TB) and its co-morbid conditions have become a burden on global health economies. It is well understood that susceptibility of the host to TB infection/disease is influenced by both genetic and environmental factors and their interactions. The aims of this pilot case-control study are to characterize the sociodemographic and environmental factors related to active TB disease (TB/case) and latent TB infection (LTBI/control) status, and to identify risk factors associated with progression from LTBI to TB. We recruited 75 cases with TB (mean age=46.3y; females=41%) and 75 controls with LTBI (mean age=39.0y; females=37%), from the Mestizo population of Cuidad Juárez, Mexico. In addition to the determination of case/control status, information on environmental variables was collected (e.g., socioeconomic status, smoking, alcohol consumption, substance abuse, nutritional status, household demographics, medical histories and presence of type 2 diabetes [T2DM]). The data were analyzed to identify the environmental correlates of TB and LTBI using univariate and multivariate statistical approaches. Following multivariate logistic regression analysis, TB was associated with poor nutrition, T2DM, family history of TB, and non-Chihuahua state of birth. These preliminary findings have relevance to TB control at the Mexico-United States border, and contribute to our future genetic study of TB in Mexicans.

Antioxidant supplementation has a positive effect on oxidative stress and hematological toxicity during oncology treatment in cervical cancer patients.

BACKGROUND AND AIM: Hematological toxicity and oxidative stress are common in cancer patients. Antioxidant supplementation has been shown to decrease oxidative stress, but there is still controversy on this topic. The aim of this study was to determine the effect of antioxidant supplementation on oxidative stress, hematological toxicity, and quality of life (QoL) in cervical cancer patients. METHODS: Randomized, single-blinded controlled trial in women with cervical cancer treated with radiotherapy and chemotherapy with cisplatin. Subjects were randomly assigned to receive antioxidant supplement or placebo supplement. Plasma concentrations of malondialdehyde, free carbonyls, and blood biometry were measured. EORTC quality of life questionnaire was applied before and after oncology treatment. Student's t test for independent samples and X (2) for categorical variables were performed. RESULTS: One hundred three patients were randomly assigned to receive treatment with antioxidants 49 (48 %) or placebo 54 (52.40 %). At the end of the oncology treatment, hemoglobin levels were maintained, and global QoL was better only in the supplemented group (p < 0.025). CONCLUSIONS: Antioxidant supplementation in patients treated with chemotherapy and radiotherapy apparently decreased oxidative stress, maintained hemoglobin levels, and improved QoL; however, more studies are needed to study the long-term effect of this intervention.

Lower serum IL-10 is an independent predictor of IBS among volunteers in Mexico.

OBJECTIVES: Studies suggest that altered immune activation, manifested by an imbalance in anti- and pro-inflammatory cytokine levels, exists in a subgroup of irritable bowel syndrome (IBS) patients. However, similar studies have not been conducted in Latin populations. The objective of this study was to measure serum levels of interleukin (IL)-10 and tumor necrosis factor (TNF)-α in subjects fulfilling symptom criteria for IBS and controls. METHODS: Volunteers (n=178) from a university population in Mexico City, participated in the study. Of the sample, 34.8% met Rome II criteria for IBS and 65.2% were designated as controls. Serum cytokines were measured by enzyme-linked immunoabsorbent assay. Analysis of covariance models were used to test main effects between gender, IBS symptoms, and bowel habit subtype to explain the cytokine serum levels. Statistical models were tested using body mass index as a covariate. RESULTS: IL-10 levels were significantly lower in IBS vs. controls (mean (95% confidence interval): 15.6 (14.8, 16.3) vs. 18.6 (17.9, 19.4) pg/ml, P<0.001), while TNF-α levels were higher in IBS (20.9 (19.1, 23.0) vs. 17.9 (16.7, 19.3) pg/ml, P=0.010). IBS and female gender were independent predictors for IL-10 (P<0.05). In contrast, female gender was an independent predictor for TNF-α. In addition, women with IBS-D had the lowest IL-10 (P<0.001) and highest TNF-α (P=0.021) vs. other subtypes. CONCLUSIONS: The lower serum IL-10 in our subjects fulfilling IBS Rome II symptom criteria suggests an altered immune regulation. Further studies are needed to elucidate if a lower serum IL-10 may be useful as a biomarker for IBS in the Mexican population, especially for women with IBS-D.

[Transciptome among Mexicans: a large scale methodology to analyze the genetics expression profile of simultaneous samples in muscle, adipose tissue and lymphocytes obtained from the same individual]. / Transcriptoma en mexicanos: metodología para analizar el perfil de expresión genética de gran escala en muestras simultáneas de tejido muscular, adiposo y linfocitos obtenidas en un mismo individuo.

OBJECTIVE: We describe the methodology used to analyze multiple transcripts using microarray techniques in simultaneous biopsies of muscle, adipose tissue and lymphocytes obtained from the same individual as part of the standard protocol of the Genetics of Metabolic Diseases in Mexico: GEMM Family Study. METHODS: We recruited 4 healthy male subjects with BM1 20-41, who signed an informed consent letter. Subjects participated in a clinical examination that included anthropometric and body composition measurements, muscle biopsies (vastus lateralis) subcutaneous fat biopsies anda blood draw. All samples provided sufficient amplified RNA for microarray analysis. Total RNA was extracted from the biopsy samples and amplified for analysis. RESULTS: Of the 48,687 transcript targets queried, 39.4% were detectable in a least one of the studied tissues. Leptin was not detectable in lymphocytes, weakly expressed in muscle, but overexpressed and highly correlated with BMI in subcutaneous fat. Another example was GLUT4, which was detectable only in muscle and not correlated with BMI. Expression level concordance was 0.7 (p< 0.001) for the three tissues studied. CONCLUSIONS: We demonstrated the feasibility of carrying out simultaneous analysis of gene expression in multiple tissues, concordance of genetic expression in different tissues, and obtained confidence that this method corroborates the expected biological relationships among LEPand GLUT4. TheGEMM study will provide a broad and valuable overview on metabolic diseases, including obesity and type 2 diabetes.

Transcriptoma en mexicanos: metodología para analizar el perfil de expresión genética de gran escala en muestras simultáneas de tejido muscular, adiposo y linfocitos obtenidas en un mismo individuo / Transciptome among Mexicans: a large scale methodology to analyze the genetics expression profile of simultaneous samples in muscle, adipose tissue and lymphocytes obtained from the same individual

Objetivo: Describir la metodología de análisis de múltiples transcritos con técnicas de microarreglo en biopsias simultáneas de tejido muscular, adiposo y sangre en un mismo individuo, como parte de la estandarización del estudio GEMM (Genética de las Enfermedades Metabólicas en México). Material y métodos: Se incluyó a cuatro sujetos con índice de masa corporal (IMC) entre 20 y 41. Se registró estatura, talla y composición corporal. Se realizó biopsia muscular (vasto lateral), de tejido adiposo subcutáneo y muestra de sangre completa. El ARN total fue extraído de los tejidos y amplificado para análisis de microarreglos. Resultados: De 48 687 potenciales transcritos, 39.4% fue detectable en al menos uno de los tejidos. La expresión de leptina no fue detectable en linfocitos, débilmente expresada en músculo, alta expresión en el tejido adiposo y correlacionó con el IMC. El GLUT4 también ilustra la especificidad para el músculo sin verse afectado por el IMC. La concordancia en la expresión de transcritos fue 0.70 (p<0.001) para los tres tejidos. Conclusiones: Fue factible cuantificar simultáneamente la expresión genética de miles de transcritos, hubo concordancia en la expresión entre diferentes tejidos obtenidos en un mismo individuo, y confiabilidad del método al reproducir las relaciones biológicas esperadas. El estudio GEMM podrá analizar las correlaciones de los transcritos expresados dentro de un órgano y luego entre diferentes tejidos, y proveerá endofenotipos cuantitativos novedosos que proporcionarán un amplio panorama de información sobre las enfermedades metabólicas, incluyendo obesidad y diabetes tipo 2.

OBJECTIVE: We describe the methodology used to analyze multiple transcripts using microarray techniques in simultaneous biopsies of muscle, adipose tissue and lymphocytes obtained from the same individual as part of the standard protocol of the Genetics of Metabolic Diseases in Mexico: GEMM Family Study. METHODS: We recruited 4 healthy male subjects with BM1 20-41, who signed an informed consent letter. Subjects participated in a clinical examination that included anthropometric and body composition measurements, muscle biopsies (vastus lateralis) subcutaneous fat biopsies anda blood draw. All samples provided sufficient amplified RNA for microarray analysis. Total RNA was extracted from the biopsy samples and amplified for analysis. RESULTS: Of the 48,687 transcript targets queried, 39.4% were detectable in a least one of the studied tissues. Leptin was not detectable in lymphocytes, weakly expressed in muscle, but overexpressed and highly correlated with BMI in subcutaneous fat. Another example was GLUT4, which was detectable only in muscle and not correlated with BMI. Expression level concordance was 0.7 (p< 0.001) for the three tissues studied. CONCLUSIONS: We demonstrated the feasibility of carrying out simultaneous analysis of gene expression in multiple tissues, concordance of genetic expression in different tissues, and obtained confidence that this method corroborates the expected biological relationships among LEPand GLUT4. TheGEMM study will provide a broad and valuable overview on metabolic diseases, including obesity and type 2 diabetes.

Reproducibilidad y sensibilidad del cuestionario Impacto del peso en la calidad de vida en mexicanos obesos / Reproducibility and sensitivity of the impact of weight on quality of life questionnaire among obese Mexicans

Objetivo: Determinar si el cuestionario “Impacto del peso en la calidad de vida” (IWQOL) es reproducible y sensible para identificar diferencias entre las clases de obesidad establecidas por la Organización Mundial de la Salud. Métodos: El IWQOL fue traducido al castellano de acuerdo a la usanza del lenguaje en México pero manteniendo un vocabulario amplio para América Latina. Investigamos la reproducibilidad del cuestionario por el método de prueba-reprueba (n=82, IMC=37.8±8.4), la sensibilidad para identificar diferencias entre los grados de la obesidad (n=105, IMC=35.1±9.5) y la sensibilidad para detectar diferencias después de recibir algún tratamiento para la pérdida del peso (n=40, IMC=39.2±7). Resultados: El IWQOL mostró buena reproducibilidad y sensibilidad para identificar diferencias entre grupos de obesos y cambios luego de tratamiento. Todos los dominios fueron reproducibles (criterio a priori: la diferencia entre prueba re-prueba no debía ser mayor de 5 puntos porcentuales) y tuvieron alta validez interna (coeficiente alfa de Cronbach>0.92 para todos los dominios). El IWQOL detectó diferencias entre los grupos divididos por la severidad de la obesidad, siendo los más afectados aquellos con IMC>45. Los sujetos sometidos a tratamiento perdieron 6.4 kg (IC95%=4.6-8.2) durante un periodo de 2.70±1 meses e incrementaron la calificación en todos los dominios, excepto el correspondiente a “trabajo”. Conclusiones: El cuestionario IWQOL es una herramienta confiable y sensible que se puede utilizar para la investigación de la calidad de vida en mexicanos y probablemente en la mayoría de las poblaciones latinoamericanas. Nuestro estudio es el primero envalidar el IWQOL en México.

OBJECTIVE: Determine if the Spanish version of the IWQOL (Impact of Weight on Quality of Life) questionnaire is reproducible and sensitive to detect differences among WHO's classification of obesity. METHODS: The IWQOL was translated into Spanish and adapted to the Mexican context while maintaining a wide comprehensive vocabulary applicable to Latin American countries. We measured reproducibility using a test-retest method (n=82, BMI 37.8+/-8.4), sensitivity to detect differences between types of obesity (n=105, BMI 35.1+/-9.5), and sensitivity to detect differences after treatment for weight loss within groups (n=40, BMI 39.2+/-7). RESULTS: The IWQOL questionnaire was reliable and sensitive enough to detect differences among and within groups. All domains were highly reproducible (scores differed by less than 2 points) and had high internal validity (Cronbach alpha coefficient >0.92 for all scales). The IWQOL detected differences between groups stratfied by severity of obesity, the lowest score was for BMI >45. Subjects who underwent weight loss treatment and lost 6.4 kg (95% CI 4.6, 8.2) during a period of 2.70+/-1 month had an improvement in all scales except for the [quot ]Work[quot ] domain. CONCLUSIONS: The IWQOL questionnaire is a reliable and sensitive tool that can be used for research purposes in Mexico and the Latin America region. Our study validates the use of IWQOL among Mexican subjects.

Macrófagos, inflamación, tejido adiposo, obesidad y resistencia a la insulina / Macrophages, inflammation, adipose tissue, obesity and insulin resistance

La obesidad se asocia con un estado inflamatorio implicado en el desarrollo de aterosclerosis y resistencia a la insulina. Los macrófagos son claves en la génesis de estos procesos. La obesidad induce la acumulación de macrófagos en el tejido adiposo. Los macrófagos producen muchas de las moléculas inflamatorias secretadas por el tejido adiposo. Las proteínas quimioatrayentes de monocitos (MCP) y sus receptores son fundamentales en la respuesta inflamatoria y en el reclutamiento de células inmunes en sitios de inflamación. La expresión en el tejido adiposo de una MCP, la quimiocina del ligando 2 del motif C-C (CCL2 o MCP1), está incrementada en proporción a la adiposidad. El receptor 2 de quimiocina del motif C-C (CCR2) regula el reclutamiento y quimiotaxis de monocitos y macrófagos, es necesario para las respuestas inflamatorias dependientes de macrófagos y para el desarrollo de aterosclerosis. Ya que el receptor CCR2 regula las respuestas inflamatorias locales, se ha postulado que las MCP, actuando a través de su receptor CCR2, podrían regular la inflamación inducida por la obesidad en el tejido adiposo. Este documento se enfoca en dilucidar los mecanismos moleculares y genéticos que permiten reclutar y retener macrófagos en el tejido adiposo.

Obesity is associated with a complex systemic inflammatory reaction that has been associated with the development of atherosclerosis and insulin resistance. Obesity also induces macrophage accumulation in adipose tissue. Macrophages produce many of the pro inflammatory molecules released by adipose tissue and have been implicated in the development of obesity-induced adipose tissue inflammation. Monocyte chemoattractant proteins (MCPs) and their receptors play key roles in the development of inflammatory responses and are crucial for the recruitment of immune cells towards inflammation sites. Adipose tissue expression of at least 1 MCP, C-C motif chemokine ligand-2 (CCL2 or MCP1), increases in proportion to adiposity. The C-C motif chemokine receptor-2 (CCR2) regulates monocyte and macrophage recruitment and is necessary for macrophage-dependent inflammatory responses and the development of atherosclerosis. Because CCR2 regulates monocyte and macrophage chemotaxis and local inflammatory responses, it has been hypothesized that monocyte chemoattractant molecules acting through CCR2 might regulate obesity-induced inflammation in adipose tissue. Our study focuses on the molecular and genetic mechanisms that recruit and retain macrophages in adipose tissue.

Influencia de los padres sobre las preferencias alimentarias en niños de dos escuelas primarias con diferente estrato económico: estudio ESFUERSO / Parental influence in children's food preferences: the ESFUERSO study in two primary schools with different socioeconomic gradients

Objetivo: La mayoría de programas de prevención de obesidad en escuelas primarias fracasan. En este estudio investigamos la influencia de las preferencias alimentarias de los padres en las de sus hijos, de acuerdo con el sexo de los padres y el estrato económico de la familia. Consideramos que esta información será una herramienta útil para elaborar programas de prevención. Material y métodos: Participaron 300 niños de una escuela primaria del Estado (EPE) y 368 de una escuela privada (EPP). Cada pareja de padre y madre contestó dos cuestionarios: uno acerca de ellos mismos y otro sobre sus hijos. El cuestionario incluyó preguntas sobre el consumo de alimentos específicos, analizados por correlación canónica (CC). Resultados: Las escuelas estudiadas no mostraron diferencias en el índice de masa corporal de los padres y sus hijos, sólo en las madres (EPP 24 ± 4 vs. EPE 26 ± 4, p < 0.001). La CC indicó que las madres influyen 30% en las preferencias de sus hijos; esta asociación fue mayor en EPE. La preferencia por alimentos ricos en hidratos de carbono simples se observó sólo en los niños, sin mayor influencia de los padres. Los refrescos regulares mostraron alta preferencia en ambas escuelas; el refresco de dieta es preferido por EPP, pero ambas escuelas prefieren no dar refresco de dieta a los niños. Conclusiones: Existen diferencias de estrato económico y sexo de los padres, que influyen en las preferencias alimentarias de los niños. Los programas de prevención de obesidad deberán considerar las preferencias alimentarias de los padres para aumentar el impacto en los niños.

OBJECTIVE: Programs aimed at obesity prevention among elementary school age children have failed. In the present study, we analyzed the association between parental and child food preferences and determined whether this is influenced by the parents' gender and socio-economic status. MATERIAL AND METHODS: We invited 300 children from a state elementary school (SES) and368 from a private middle class school (PMCS) to participate. A questionnaire was given to each parent to complete together with another questionnaire asking questions about their child. The questionnaire included items on consumption of specific foods. Canonical correlation coefficients (CC) were calculated to assess the association between children's food preferences and their parents' food preferences. RESULTS: Mothers from the PMCS group had lower Body Mass Index (BMIs) than mothers from the SES (24 +/- 4 vs. 26 +/- 4, p < 0.001). Fathers and children from the PMCS group were taller and weighed more than those from the SES but their BMI's were similar. CC indicate that mothers influence their children's food preferences by 30%, and this association is stronger in the SES group. Preference for simple carbohydrates was observed among children without parental supervision. Regular soft drinks were preferred by children in both schools, but diet sodas were more common among PMCS. All families avoided giving their children diet soft drinks. CONCLUSIONS: Socio-economic status and gender diferentially influence children's meal preferences. Obsesity prevention programs should take into account parental food preferences as an important factor that determines obesity during childhood. We expect that our results will contribute to the design of more appropriate prevention programs.

El grado de obesidad modifica la respuesta de disminución de circunferencia de cintura en pacientes que reciben 15 mg diarios de sibutramina: estudio abierto sobre tolerancia y efectividad de la sibutramina / Patients with type III obesity given sibutramine 15 mg/day lose weight in amounts proportional to those in types I and II, but waist circumferences does not decrease proportionally

Objetivo. Los pacientes con sobrepeso y las clases de obesidad I, II, III presentan diferente etiología, comorbilidad, efectos metabólicos y diferente respuesta terapéutica. En este análisis evaluamos el efecto del grado de obesidad sobre la disminución del índice de masa corporal (IMC) y la circunferencia de cintura (CC) eficacia y tolerancia de sibutramina 15mg al día. Material y métodos. Se analizó una base de datos de una muestra de 701 sujetos colectados de 47 clínicas. Los sujetos recibieron tratamiento con 15 mg de sibutramina al día. Se registró el peso, estatura y la CC en las visitas basal, 4 y 8 semanas. Resultados. Los pacientes con diferentes grados de obesidad disminuyeron proporcionalmente el IMC (p = 0.86), pero los sujetos con obesidad clase III mostraron menor disminución de la CC (p = 0.003) que los otros grupos. Los eventos adversos fueron pocos, y de menor frecuencia con grados mayores de obesidad. Discusión. La disociación de disminución de IMC y la CC puede estar relacionada al control ejercido por el sistema simpático de acuerdo con el grado de obesidad, además de la biodistribución de sibutramina. Los sujetos con IMC mayor de 40 necesitan mayor dosis para alcanzar proporcionalmente la pérdida de grasa abdominal de los otros grupos de obesos.

OBJECTIVE: The etiology, comorbidity, metabolism, and treatment response vary among overweight and obesity types I, II and III individuals. We assessed the association between obesity type with body mass index, waist circumference and tolerance to a daily dose of 15 mg of sibutramine. MATERIALS AND METHODS: A sample of 701 individuals recruited from 47 health centers was analyzed. All subjects received 15 mg of sibutramine daily for 8 weeks. Weight, height, and waist circumference were measured at day 0 and weeks 4 and 8. RESULTS: Patients in all obesity types lost proportional amounts of weight (p=0.86), but those in type IIl obesity had a smaller reduction in waist circumference than those in types I and 1 (p=0.003). Side effects of sibutramine were rarely observed. Subjects with type III obesity exhibited even fewer side effects. CONCLUSIONS: The lack of association between weight reduction and decreased waist circumference across obesity types could be related to differences in the sympathetic nervous system or to sibutramine biodistribution. Subjects with body mass index greater than 40 Kg/ m(2) required a higher dose of sibutramine in order to loose the same proportion of abdominal fat as those in other types of obesity.

[Macrophages, inflammation, adipose tissue, obesity and insulin resistance]. / Macrófagos, inflamación, tejido adiposo, obesidad y resistencia a la insulina.

Obesity is associated with a complex systemic inflammatory reaction that has been associated with the development of atherosclerosis and insulin resistance. Obesity also induces macrophage accumulation in adipose tissue. Macrophages produce many of the pro inflammatory molecules released by adipose tissue and have been implicated in the development of obesity-induced adipose tissue inflammation. Monocyte chemoattractant proteins (MCPs) and their receptors play key roles in the development of inflammatory responses and are crucial for the recruitment of immune cells towards inflammation sites. Adipose tissue expression of at least 1 MCP, C-C motif chemokine ligand-2 (CCL2 or MCP1), increases in proportion to adiposity. The C-C motif chemokine receptor-2 (CCR2) regulates monocyte and macrophage recruitment and is necessary for macrophage-dependent inflammatory responses and the development of atherosclerosis. Because CCR2 regulates monocyte and macrophage chemotaxis and local inflammatory responses, it has been hypothesized that monocyte chemoattractant molecules acting through CCR2 might regulate obesity-induced inflammation in adipose tissue. Our study focuses on the molecular and genetic mechanisms that recruit and retain macrophages in adipose tissue.

[Relationship between morphological diagnosis of NASH (non-alcoholic steatohepatitis) and liver function tests in a group of patients with morbid obesity]. / Relación entre el diagnóstico morfológico de EHNA (esteatohepatitis no alcohólica) y pruebas de función hepática en un grupo de pacientes con obesidad extrema.

UNLABELLED: The non-alcoholic steato-hepatitis (NASH) is a common disorder in obese, type 2 diabetics, female and patients with dislipidaemia. Hepatic biochemical test are abnormal. Despite the lack of its own morphological characteristics, NASH can be differentiated from other pathologies, the gold standard for diagnosis is liver biopsy. MATERIAL AND METHODS: We designed a retrolective, comparative, observational and cross-sectional study. Thirty-five obese subjects (11 men and 24 women) who underwent to bariatric surgery and liuer biopsy were included. Data were taken from clinical files, such as anthropometric and biochemical test. Those who had clinical history of related alcohol ingestion or liver damage related to drugs were excluded. A experimented pathologist classified the biopsies according to Brunt classification. Liver slides were classified according to 1) presence of NASH; 2) Inflammation and 3) Fibrosis. Differences between groups were analysed by ANOVA and Spearman correlation. RESULTS: We found differences between women (w) and men (m) for height (m: 1.71 +/- 0.9 vs. w:1.60 +/- 0.09m); weight (m:172.5 +/- 39.1 vs. w:126.9 +/- 24.1kg) and BMI (m:58.2 +/- 9.8 vs. w:49.8 +/- 9) , but not for NASH frequency. Nevertheless subjects with NASH (n = 29, 82.8%o) were older than those without NASH (38.3 +/- 9.6 vs. 29.5 +/- 5.2) and had higher aminotrasferases serum levels (AST: 33.1 +/- 19.2 vs. 23.7 +/- 6.3 ULIL; ALT: 36.5 +/- 19.8 vs. 20.3 +/- 7.6ULIL). NASH pa- tients and those with higher grade of histological inflammation had increment of transaminases and albumin levels. Fibrosis showed correlation only with AST (p = 0.020) and ALT (p = 0.002). CONCLUSION: The NASH frequency in patients who underwent to bariatric surgery for weight reduction is very high (82.8%) and exists correlation among liver test and histological findings but not with clinical because the clinical diagnosis is complicated.