Publications by authors named "Juan Carlos Lopez-Alvarenga"

54 Publications

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

Cardiovasc Diabetol 2021 04 21;20(1):80. Epub 2021 Apr 21.

Diabetes and Cardiovascular Center, University of Missouri School of Medicine, Columbia, MO, USA.

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•day; ZOSV); Group 3: valsartan (31 mg•kg•day; ZOV) and Group 4: hydralazine, an anti-hypertensive drug (30 mg•kg•day; 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.
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http://dx.doi.org/10.1186/s12933-021-01270-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061206PMC
April 2021

Neuropsychiatric Symptoms Among Hispanics: Results of the Maracaibo Aging Study.

J Alzheimers Dis 2021 Feb 19. Epub 2021 Feb 19.

Department of Neuroscience, School of Medicine, University of Texas Rio Grande Valley, Harlingen, TX, USA.

Background: Neuropsychiatric symptoms play an important role in diagnosing and clinical follow-up of cognitive impairment and dementia.

Objective: We investigated the relationship between neuropsychiatric symptoms, cognitive impairment, and dementia in Hispanics.

Methods: We included 529 participants (age ≥40 years) from the Maracaibo Aging Study with standardized neuropsychiatric assessments, including the Neuropsychiatric Inventory (NPI). Based on the Clinical Dementia Rating and the Mini-Mental State Examination scores, participants' cognitive status was categorized into normal cognition, mild/moderate, and severe cognitive impairment. Diagnosis of dementia was established in a consensus conference. Statistical analyses included multivariable logistic regression models and area under the curve (AUC).

Results: The mean age of participants was 59.3 years, and 71.8%were women. The proportion of dementia was 6.8%. Disturbed sleep, anxiety, and depression were the most common neuropsychiatric symptoms in the study sample. In crude analyses, the proportions of hallucinations, aberrant motor behavior, agitation/aggression, apathy, delusions, irritability, eating disturbance, depression, and euphoria were differently distributed among cognitive status groups (p <  0.05). After accounting for confounders, aberrant motor behavior and agitation/aggression remained significantly associated with cognitive impairment and dementia (p <  0.05). The inclusion of the NPI domains significantly improved the AUC to discriminate severe cognitive impairment and dementia above of a basic model that included sex, age, education, alcohol, obesity, serum glucose, total cholesterol, hypertension, and stroke.

Conclusion: Neuropsychiatric symptoms are associated with severe cognitive impairment and dementia. The addition of NPI items to the global cognitive assessment might help early detection of dementia in primary care settings.
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http://dx.doi.org/10.3233/JAD-201144DOI Listing
February 2021

Further evidence supporting a potential role for ADH1B in obesity.

Sci Rep 2021 Jan 21;11(1):1932. Epub 2021 Jan 21.

South Texas Diabetes and Obesity Institute Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Edinburg/Harlingen/Brownsville, TX, USA.

Insulin is an essential hormone that regulates glucose homeostasis and metabolism. Insulin resistance (IR) arises when tissues fail to respond to insulin, and it leads to serious health problems including Type 2 Diabetes (T2D). Obesity is a major contributor to the development of IR and T2D. We previously showed that gene expression of alcohol dehydrogenase 1B (ADH1B) was inversely correlated with obesity and IR in subcutaneous adipose tissue of Mexican Americans. In the current study, a meta-analysis of the relationship between ADH1B expression and BMI in Mexican Americans, African Americans, Europeans, and Pima Indians verified that BMI was increased with decreased ADH1B expression. Using established human subcutaneous pre-adipocyte cell lines derived from lean (BMI < 30 kg m) or obese (BMI ≥ 30 kg m) donors, we found that ADH1B protein expression increased substantially during differentiation, and overexpression of ADH1B inhibited fatty acid binding protein expression. Mature adipocytes from lean donors expressed ADH1B at higher levels than obese donors. Insulin further induced ADH1B protein expression as well as enzyme activity. Knockdown of ADH1B expression decreased insulin-stimulated glucose uptake. Our findings suggest that ADH1B is involved in the proper development and metabolic activity of adipose tissues and this function is suppressed by obesity.
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http://dx.doi.org/10.1038/s41598-020-80563-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820614PMC
January 2021

Serum carotenoids and Pediatric Metabolic Index predict insulin sensitivity in Mexican American children.

Sci Rep 2021 Jan 13;11(1):871. Epub 2021 Jan 13.

Department of Food Science, Pennsylvania State University, University Park, PA, USA.

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and β-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and β-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and β-cryptoxanthin were highly heritable [h = 0.98, P = 7 × 10 and h = 0.58, P = 1 × 10]. We found significant (P ≤ 0.05) negative phenotypic correlations between β-cryptoxanthin and five CMTs: body mass index (- 0.22), waist circumference (- 0.25), triglycerides (- 0.18), fat mass (- 0.23), fasting glucose (- 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (- 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and β-carotenoids rather than that of β-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.
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http://dx.doi.org/10.1038/s41598-020-79387-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806924PMC
January 2021

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study.

Adipocyte 2020 12;9(1):153-169

Departamento de Nutrición Humana, Universidad Latina de América, Morelia, México.

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders.
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http://dx.doi.org/10.1080/21623945.2020.1743116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153654PMC
December 2020

Gender-specific differences in clinical and metabolic variables associated with NAFLD in a Mexican pediatric population.

Ann Hepatol 2019 Sep - Oct;18(5):693-700. Epub 2019 May 22.

Pediatric Obesity Clinic, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico; School of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico; Department of Human Genetics, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico. Electronic address:

Introduction And Objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and it is more prevalent in Hispanic males. The gender differences can be explained by body fat distribution, lifestyle, or sex hormone metabolism. We evaluated anthropometric and metabolic differences by gender in children with and without NAFLD.

Methods: We included 194 participants (eutrophic, overweight, and individuals with obesity). The presence of NAFLD was determined using ultrasonography, and we evaluated the association between this disease with metabolic and anthropometric variables by gender.

Results: The mean age was 10.64±2.54 years. The frequency of NAFLD in boys was 24.51% and in girls was 11.96% (OR=2.39; 95%CI=1.10-5.19; p=0.025). For girls, NAFLD was significantly associated with triglycerides (p=0.012), homeostatic model assessment of insulin resistance (HOMA-IR) (p=0.048), and the visceral adiposity index (VAI) (p=0.024). The variables related to NAFLD in a gender-specific manner were body mass index (BMI) (p=0.001), waist circumference (WC) (p<0.001), HDL cholesterol (p=0.021), alanine aminotransferase (ALT) (p<0.001), and aspartate aminotransferase (AST) (p=0.002).

Conclusions: In our study NAFLD is more frequent in boys, only ALT, and no other clinical or metabolic variables, were associated with NAFLD in these patients. HOMA-IR, VAI, triglyceride levels, and ALT were associated with NAFLD only in girls. The ALT cut-off points for the development of NAFLD in our study were 28.5U/L in females and 27.5U/L in males. Our findings showed that NAFLD should be intentionally screened in patients with obesity, particularly in boys.
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http://dx.doi.org/10.1016/j.aohep.2019.04.012DOI Listing
August 2020

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

Tuberculosis (Edinb) 2018 12 18;113:10-18. Epub 2018 Aug 18.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Mater Research Institute - The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia. Electronic address:

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.
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http://dx.doi.org/10.1016/j.tube.2018.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284235PMC
December 2018

PEDIATRIC VISCERAL ADIPOSITY INDEX ADAPTATION CORRELATES WITH HOMA-IR, MATSUDA, AND TRANSAMINASES.

Endocr Pract 2018 Mar;24(3):294-301

Objective: Visceral adiposity index (VAI) is a mathematical model associated with cardiometabolic risk in adults, but studies on children failed to support this association. Our group has proposed a pediatric VAI model using pediatric ranges, but it has not yet been evaluated and needs further adjustments. The objective of this study was to further adjust the proposed pediatric VAI by age, creating a new pediatric metabolic index (PMI), and assess the correlation of the PMI with insulin resistance indexes and hepatic enzymes.

Methods: A cross-sectional design with data from 396 children (age 5 to 17 years) was analyzed with a generalized linear model to find the coefficients for triglycerides, high-density-lipoprotein cholesterol, and waist circumference-body mass index quotient. The model was constructed according to sex and age and designated PMI. A cross-validation analysis was performed and a receiver operating characteristic curve was used to determine cut-off points.

Results: Significant moderate correlation was found between PMI and homeostatic model assessment of insulin resistance (HOMA-IR) ( r = 0.452; P = .003), Matsuda ( r = -0.366; P = .019), alanine aminotransferase ( r = 0.315, P = .045), and γ-glutamyltransferase ( r = 0.397; P = .010). A PMI score >1.7 was considered as risk.

Conclusion: PMI correlates with HOMA-IR, Matsuda, and hepatic enzymes. It could be helpful for identifying children at risk for cardiometabolic diseases.

Abbreviations: ALT = alanine transaminase BMI = body mass index GGT = γ-glutamyltransferase HDL-C = high-density-lipoprotein cholesterol HOMA-IR = homeostatic model assessment of insulin resistance hs-CRP = high sensitivity C-reactive protein ISI = insulin sensitivity index NAFLD = nonalcoholic fatty liver disease PMI = pediatric metabolic index QUICKI = quantitative insulin sensitivity check index ROC = receiver operating characteristic TG = triglyceride TNF-α = tumor necrosis factor-alpha VAI = visceral adiposity index VAT = visceral adipose tissue WC = waist circumference.
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http://dx.doi.org/10.4158/EP-2017-0086DOI Listing
March 2018

Family history and obesity in youth, their effect on acylcarnitine/aminoacids metabolomics and non-alcoholic fatty liver disease (NAFLD). Structural equation modeling approach.

PLoS One 2018 21;13(2):e0193138. Epub 2018 Feb 21.

South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Edinburg, TX, United States of America.

Background: Structural equation modeling (SEM) can help understanding complex functional relationships among obesity, non-alcoholic fatty liver disease (NAFLD), family history of obesity, targeted metabolomics and pro-inflammatory markers. We tested two hypotheses: 1) If obesity precedes an excess of free fatty acids that increase oxidative stress and mitochondrial dysfunction, there would be an increase of serum acylcarnitines, amino acids and cytokines in obese subjects. Acylcarnitines would be related to non-alcoholic fatty disease that will induce insulin resistance. 2) If a positive family history of obesity and type 2 diabetes are the major determinants of the metabolomic profile, there would be higher concentration of amino acids and acylcarnitines in patients with this background that will induce obesity and NAFLD which in turn will induce insulin resistance.

Methods/results: 137 normoglycemic subjects, mean age (SD) of 30.61 (8.6) years divided in three groups: BMI<25 with absence of NAFLD (G1), n = 82; BMI>30 with absence of NAFLD (G2), n = 24; and BMI>30 with NAFLD (G3), n = 31. Family history of obesity (any) was present in 53%. Both models were adjusted in SEM. Family history of obesity predicted obesity but could not predict acylcarnitines and amino acid concentrations (effect size <0.2), but did predict obesity phenotype.

Conclusion: Family history of obesity is the major predictor of obesity, and the metabolic abnormalities on amino acids, acylcarnitines, inflammation, insulin resistance, and NAFLD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193138PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821462PMC
May 2018

Heritability and genetic correlation between GERD symptoms severity, metabolic syndrome, and inflammation markers in families living in Mexico City.

PLoS One 2017 5;12(6):e0178815. Epub 2017 Jun 5.

South Texas Diabetes and Obesity Institute. University of Texas Rio Grande Valley, Edinburg, TX, United States of America.

Objective: The aim of this study was to estimate the heritability (h2) and genetic correlation (ρG) between GERD symptoms severity, metabolic syndrome components, and inflammation markers in Mexican families.

Methods: Cross-sectional study which included 32 extended families resident in Mexico City. GERD symptoms severity was assessed by the ReQuest in Practice questionnaire. Heritability and genetic correlation were determined using the Sequential Oligogenic Linkage Analysis Routines software.

Results: 585 subjects were included, the mean age was 42 (±16.7) years, 57% were women. The heritability of the severity of some GERD symptoms was h2 = 0.27, 0.27, 0.37, and 0.34 (p-value <1.0x10-5) for acidity complaints, lower abdominal complaints, sleep disturbances, and total ReQuest score, respectively. Heritability of metabolic syndrome components ranged from 0.40 for fasting plasma glucose to 0.61 for body mass index and diabetes mellitus. The heritability for fibrinogen and C-reactive protein was 0.64 and 0.38, respectively. Statistically significant genetic correlations were found between acidity complaints and fasting plasma glucose (ρG = 0.40); sleep disturbances and fasting plasma glucose (ρG = 0.36); acidity complaints and diabetes mellitus (ρG = 0.49) and between total ReQuest score and fasting plasma glucose (ρG = 0.43). The rest of metabolic syndrome components did not correlate with GERD symptoms.

Conclusion: Genetic factors substantially explain the phenotypic variance of the severity of some GERD symptoms, metabolic syndrome components and inflammation markers. Observed genetic correlations suggest that these phenotypes share common genes. These findings suggest conducting further investigation, as the determination of a linkage analysis in order to identify regions of susceptibility for developing of GERD and metabolic syndrome.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178815PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459455PMC
September 2017

Genetics of serum carotenoid concentrations and their correlation with obesity-related traits in Mexican American children.

Am J Clin Nutr 2017 Jul 17;106(1):52-58. Epub 2017 May 17.

Food Science and

Dietary intake of phytonutrients present in fruits and vegetables, such as carotenoids, is associated with a lower risk of obesity and related traits, but the impact of genetic variation on these associations is poorly understood, especially in children. We estimated common genetic influences on serum carotenoid concentrations and obesity-related traits in Mexican American (MA) children. Obesity-related data were obtained from 670 nondiabetic MA children, aged 6-17 y. Serum α- and β-carotenoid concentrations were measured in ∼570 (α-carotene in 565 and β-carotene in 572) of these children with the use of an ultraperformance liquid chromatography-photodiode array. We determined heritabilities for both carotenoids and examined their genetic relation with 10 obesity-related traits [body mass index (BMI), waist circumference (WC), high-density lipoprotein (HDL) cholesterol, triglycerides, fat mass (FM), systolic and diastolic blood pressure, fasting insulin and glucose, and homeostasis model assessment of insulin resistance] by using family data and a variance components approach. For these analyses, carotenoid values were inverse normalized, and all traits were adjusted for significant covariate effects of age and sex. Carotenoid concentrations were highly heritable and significant [α-carotene: heritability () = 0.81, = 6.7 × 10; β-carotene: = 0.90, = 3.5 × 10]. After adjusting for multiple comparisons, we found significant ( ≤ 0.05) negative phenotypic correlations between carotenoid concentrations and the following traits: BMI, WC, FM, and triglycerides (range: α-carotene = -0.19 to -0.12; β-carotene = -0.24 to -0.13) and positive correlations with HDL cholesterol (α-carotene = 0.17; β-carotene = 0.24). However, when the phenotypic correlations were partitioned into genetic and environmental correlations, we found marginally significant ( = 0.051) genetic correlations only between β-carotene and BMI (-0.27), WC (-0.30), and HDL cholesterol (0.31) after accounting for multiple comparisons. None of the environmental correlations were significant. The findings from this study suggest that the serum carotenoid concentrations were under strong additive genetic influences based on variance components analyses, and that the common genetic factors may influence β-carotene and obesity and lipid traits in MA children.
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http://dx.doi.org/10.3945/ajcn.116.144006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486195PMC
July 2017

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

J Nutr Biochem 2017 05 10;43:98-106. Epub 2017 Feb 10.

Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jnutbio.2017.02.002DOI Listing
May 2017

The effect size of type 2 diabetes mellitus on tuberculosis drug resistance and adverse treatment outcomes.

Tuberculosis (Edinb) 2017 03 24;103:83-91. Epub 2017 Jan 24.

Public Health Institute, University of Veracruz, Veracruz, Mexico; Red multidisciplinaria de Investigación en tuberculosis, Mexico. Electronic address:

Objective: To evaluate the effect size of type 2 diabetes mellitus (T2DM) on tuberculosis (TB) treatment outcomes and multi drug resistance (MDR).

Methods: A cohort with 507 individuals with diagnosed TB included 183 with coexistence of T2DM and TB (TB-T2DM). Participants were identified at the time of TB diagnosis and followed during the course of TB treatment. Then we computed relative risks and adjustments by Cox proportional hazards for outcome variables (drug resistance, death, relapse, treatment failure), and the size of their effect as Cohen's-d.

Results: Patients with TB-T2DM were more likely to remain positive for acid-fast bacilli after two months of anti-TB treatment RR = [2.01 (95% CI: 1.3, 3.1)], to have drug resistant (DR) [OR 3.5 (95% CI: 1.8, 6.7)] and multi-drug resistant (MDR) TB [OR 3.5 (95% CI: 1.8, 7.1)]. The Cohen's-d for DR or MDR in T2DM was 0.69 when compared with non-DM subjects. The T2DM patients had higher odds of resistance to isoniazid (OR 3.9, 95% CI: 2.01, 7.9), rifampicin (OR 3.4, 95% CI: 1.6, 7.2) and pyrazinamide (OR 9.4, 95% CI: 2.8, 25.6), and their effect sizes were ≥0.67. Patients with TB-T2DM (versus no DM) were more likely to present with MDR TB (HR 3.1; 95% CI: 1.7, 5.8; p < 0.001), treatment failure (HR 2.04; 95% CI: 1.07, 3.8; p = 0.02) and relapse (HR 1.86; 95% CI: 1.09, 3.1; p = 0.02), with effect size ≥0.34.

Conclusion: T2DM showed a substantial contribution to the presence of DR or MDR-TB and to adverse clinical outcomes during and after TB treatment. Our findings support the importance for routine screening of T2DM among newly-diagnosed TB patients in order to stratify them for immediate DR assessment, and highlight the need for clinical trials to evaluate variations to the standard TB treatment in TB-T2DM to prevent adverse treatment outcomes.
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http://dx.doi.org/10.1016/j.tube.2017.01.006DOI Listing
March 2017

Effects of Conjugated Linoleic Acid and Metformin on Insulin Sensitivity in Obese Children: Randomized Clinical Trial.

J Clin Endocrinol Metab 2017 01;102(1):132-140

School of Medicine, South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Edinburg, Texas 78539.

Context: Insulin resistance precedes metabolic syndrome abnormalities and may promote cardiovascular disease and type 2 diabetes in children with obesity. Results of lifestyle modification programs have been discouraging, and the use of adjuvant strategies has been necessary.

Objective: This study aimed to evaluate the effects of metformin and conjugated linoleic acid (CLA) on insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp technique and insulin pathway expression molecules in muscle biopsies of children with obesity.

Design: A randomized, double-blinded, placebo-controlled clinical trial was conducted.

Setting: Children with obesity were randomly assigned to receive metformin, CLA, or placebo.

Results: Intervention had a positive effect in all groups. For insulin sensitivity Rd value (mg/kg/min), there was a statistically significant difference between the CLA vs placebo (6.53 ± 2.54 vs 5.05 ± 1.46, P = 0.035). Insulinemia and homeostatic model assessment of insulin resistance significantly improved in the CLA group (P = 0.045). After analysis of covariance was performed and the influence of body mass index, age, Tanner stage, prescribed diet, and fitness achievement was controlled, a clinically relevant effect size on insulin sensitivity remained evident in the CLA group (37%) and exceeded lifestyle program benefits. Moreover, upregulated expression of the insulin receptor substrate 2 was evident in muscle biopsies of the CLA group.

Conclusions: Improvement of insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp and IRS2 upregulation, favored patients treated with CLA.
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http://dx.doi.org/10.1210/jc.2016-2701DOI Listing
January 2017

The effects of resistance exercise and oral nutritional supplementation during hemodialysis on indicators of nutritional status and quality of life.

Nephrol Dial Transplant 2016 10 10;31(10):1712-20. Epub 2016 Aug 10.

Departamento de Nefrología y Metabolismo Mineral, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico Departamento de Atención a la Salud, Universidad Autonoma Metropolitana Unidad Xochimilco, Mexico DF, Coyoacán, Mexico.

Background: Protein-energy wasting (PEW) is common in patients undergoing hemodialysis (HD). Studies have assessed the positive effect of oral nutritional supplementation (ONS) or resistance exercise (RE) on nutritional status (NS) markers in patients undergoing HD.

Methods: The aim of this study was to assess the effect of ONS and RE on NS and the quality of life (QOL) of 36 patients undergoing HD. In a randomized clinical trial, patients were divided into the following two groups: a control group (ONS) that received a can of ONS during their HD sessions and an intervention group (ONS + RE) that received a can of ONS and underwent a 40-min session of RE during their HD sessions. Both interventions lasted 12 weeks. The patients' anthropometric, biochemical, dietetic and bioelectrical impedance measurements as well as their QOL, evaluated using the Kidney Disease Quality of Life Short Form, were recorded.

Results: At baseline, 55.5% of patients presented with PEW according to International Society of Renal Nutrition and Metabolism criteria (20 patients). We found statistically significant changes from baseline in both groups, such as increases in body weight, body mass index, midarm circumference, midarm muscle circumference, triceps skinfold thickness, fat mass percentage, handgrip strength, phase angle and serum albumin. A decrease in the prevalence of PEW was observed in both groups at the end of the intervention. A delta comparison between groups showed no statistically significant differences in the anthropometric and biochemical parameters. No significant improvement was observed in QOL and body composition measured by bioimpedance vector analysis. Dietary energy and protein intake increased significantly during the study period for all patients.

Conclusion: Oral nutritional supplementation during HD improves NS. The addition of RE during HD does not seem to augment the acute anabolic effects of intradialytic ONS on NS.
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http://dx.doi.org/10.1093/ndt/gfw297DOI Listing
October 2016

Effect of Resistance Exercises on the Indicators of Muscle Reserves and Handgrip Strength in Adult Patients on Hemodialysis.

J Ren Nutr 2016 Jan 8;26(1):53-60. Epub 2015 Aug 8.

Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, México. Electronic address:

Objective: Although resistance exercise has been associated with improvement in the muscle reserves, muscle strength and quality of life in end-stage renal disease patients, the objective of this paper is to evaluate the effect of resistance exercise performed during hemodialysis sessions on the anthropometric indicators of muscle reserve and handgrip strength in sedentary malnourished patients with end-stage renal disease.

Methods: Patients were randomized to perform resistance exercise during hemodialysis sessions with ankle weights and resistance bands. The exercises were performed twice a week over the course of 12 weeks. The control group underwent a hemodialysis session alone. The outcomes measures were the following anthropometric measurements: arm muscle circumference and arm muscle area. Dynamometry was used to measure the handgrip strength.

Results: Sixty-one sedentary patients with a median age of 29 years (interquartile range [IQR] 21-39 years), and 83% presenting with some grade of malnutrition were equally randomized to either the intervention or control group. In the resistance exercise group, there was an increase in the arm muscle circumference from 233.6 (IQR 202-254) mm to 241.4 (IQR 203-264) mm (P= .001), arm muscle area from 35.9 (26-41) cm(2) to 36.6 (IQR 26-46) cm(2) (P= .002), and handgrip strength from 19.6 (IQR 11-28) kg to 21.2 (IQR 13-32) kg between the basal and final measurements (P < .05). The tolerance to exercise was adequate, and no adverse events were reported during the practical exercise.

Conclusions: Resistance exercise at least twice a week is safe and represents an opportunity for improving the muscle mass and strength in adult patients who are on hemodialysis, including in those with malnutrition.
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http://dx.doi.org/10.1053/j.jrn.2015.06.006DOI Listing
January 2016

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

PLoS One 2015 7;10(7):e0132521. Epub 2015 Jul 7.

Laboratory of Liver, Pancreas and Motility, Department of Experimental Medicine, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico; Dirección de Investigación, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132521PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494878PMC
April 2016

Apolipoprotein E isoforms 3/3 and 3/4 differentially interact with circulating stearic, palmitic, and oleic fatty acids and lipid levels in Alaskan Natives.

Nutr Res 2015 Apr 14;35(4):294-300. Epub 2015 Feb 14.

Laboratorio de Nutrigenomica y Nutrigenetica, Instituto Nacional de Medicina Genómica, México City, México. Electronic address:

Lifestyle changes in Alaskan Natives have been related to the increase of cardiovascular disease and metabolic syndrome in the last decades. Variation of the apolipoprotein E (Apo E) genotype may contribute to the diverse response to diet in lipid metabolism and influence the association between fatty acids in plasma and risk factors for cardiovascular disease. The aim of this investigation was to analyze the interaction between Apo E isoforms and plasma fatty acids, influencing phenotypes related to metabolic diseases in Alaskan Natives. A sample of 427 adult Siberian Yupik Alaskan Natives was included. Fasting glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, Apo A1, and Apo B plasma concentrations were measured using reference methods. Concentrations of 13 fatty acids in fasting plasma were analyzed by gas chromatography, and Apo E variants were identified. Analyses of covariance were conducted to identify Apo E isoform and fatty acid main effects and multiplicative interactions. The means for body mass index and age were 26 ± 5.2 and 47 ± 1.5, respectively. Significant main effects were observed for variation in Apo E and different fatty acids influencing Apo B levels, triglycerides, and total cholesterol. Significant interactions were found between Apo E isoform and selected fatty acids influencing total cholesterol, triglycerides, and Apo B concentrations. In summary, Apo E3/3 and 3/4 isoforms had significant interactions with circulating levels of stearic, palmitic, oleic fatty acids, and phenotypes of lipid metabolism in Alaskan Natives.
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http://dx.doi.org/10.1016/j.nutres.2015.02.002DOI Listing
April 2015

Replication of obesity and diabetes-related SNP associations in individuals from Yucatán, México.

Front Genet 2014 18;5:380. Epub 2014 Nov 18.

Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.

The prevalence of type 2 diabetes (T2D) is rising rapidly and in Mexicans is ~19%. T2D is affected by both environmental and genetic factors. Although specific genes have been implicated in T2D risk few of these findings are confirmed in studies of Mexican subjects. Our aim was to replicate associations of 39 single nucleotide polymorphisms (SNPs) from 10 genes with T2D-related phenotypes in a community-based Mexican cohort. Unrelated individuals (n = 259) living in southeastern Mexico were enrolled in the study based at the University of Yucatan School of Medicine in Merida. Phenotypes measured included anthropometric measurements, circulating levels of adipose tissue endocrine factors (leptin, adiponectin, pro-inflammatory cytokines), and insulin, glucose, and blood pressure. Association analyses were conducted by measured genotype analysis implemented in SOLAR, adapted for unrelated individuals. SNP Minor allele frequencies ranged from 2.2 to 48.6%. Nominal associations were found for CNR1, SLC30A8, GCK, and PCSK1 SNPs with systolic blood pressure, insulin and glucose, and for CNR1, SLC30A8, KCNJ11, and PCSK1 SNPs with adiponectin and leptin (p < 0.05). P-values greater than 0.0014 were considered significant. Association of SNPs rs10485170 of CNR1 and rs5215 of KCNJ11 with adiponectin and leptin, respectively, reached near significance (p = 0.002). Significant association (p = 0.001) was observed between plasma leptin and rs5219 of KCNJ11.
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http://dx.doi.org/10.3389/fgene.2014.00380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235406PMC
December 2014

[Metformin increases serum concentration of high molecular weight (HMW-adiponectin) in nondiabetic obese subjects].

Gac Med Mex 2014 Jul-Aug;150(4):324-33

Dirección de Investigación, Hospital General de México, México, D.F.

Introduction: Obesity is associated with low-intensity chronic systemic inflammation.

Objective: To evaluate the efficacy of two different doses of metformin in comparison with placebo on increased serum levels of high molecular weight (HMW) adiponectin.

Material And Methods: An experimental design was developed with a crossover complete treatment and balanced design; 28 female and eight male nondiabetic obese adults participated. All participants received, during a week and in randomized order: placebo or metformin 500 or 850 mg twice daily; there was a week washout period between each treatment. The HMW adiponectin serum concentration (0 and 120 minutes) at the end of each treatment was measured. Analyses of variance (ANOVA), Bonferroni test, and size effect calculations were performed.

Results: Differences in concentrations of HMW adiponectin (t0', t120') were measured for each treatment by ANOVA, having values of p = 0.03 and 0.002, respectively. The post hoc analysis reported differences favoring treatment with metformin 850 mg (p = 0.025). The sizes of the effect at times t0 and t120 for metformin 500 mg were 34 and 35%, and for metformin 850 mg, 65 and 84%, respectively.
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January 2015

[Cardiovascular exercise on obese women: effects on adiponectine, leptine, and tumour necrosis factor-alpha].

Arch Cardiol Mex 2014 Jul-Sep;84(3):177-82. Epub 2014 Aug 1.

Facultad de Enfermería, Universidad Autónoma de Nuevo León, Nuevo León, Monterrey, México.

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.
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http://dx.doi.org/10.1016/j.acmx.2013.11.007DOI Listing
May 2015

Relief of Night-time Symptoms Associated With Gastroesophageal Reflux Disease Following 4 Weeks of Treatment With Pantoprazole Magnesium: The Mexican Gastroesophageal Reflux Disease Working Group.

J Neurogastroenterol Motil 2014 Jan 30;20(1):64-73. Epub 2013 Dec 30.

Division of Gastroenterology and Hepatology, Esophageal and Swallowing Center, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA.

Background/aims: To evaluate the effectiveness of pantoprazole magnesium (pantoprazole-Mg) 40 mg in the relief of esophageal and extra-esophageal symptoms of gastroesophageal reflux disease (GERD), particularly night-time symptoms.

Methods: Patients (aged 18-50 years) with 3-month history of heartburn and/or acid regurgitation plus at least one other symptom in the last week were enrolled in a nationwide, prospective and observational study in Mexico. Patients received pantoprazole-Mg 40 mg once daily during 4 weeks. Symptoms were assessed through a physician-administered structured interview and the patient-completed ReQuest in Practice™ questionnaire. Night-time GERD was defined as arousal from sleep during the night due to GERD-associated symptoms.

Results: Out of 4,343 patients included at basal visit, 3,665 were considered for the effectiveness per protocol analysis. At baseline, patients had a median of 8 GERD related symptoms. Patients with night-time GERD symptoms (42.7%) were more likely to have extra-esophageal symptoms (P < 0.001) than other GERD patients. Pantoprazole-Mg 40 mg once daily for 4 weeks improved a broad range of GERD-associated symptoms from baseline (80% reduction on physicians assessments; 68-77% reduction on ReQuest in Practice™ dimensions), including both day- and night-time GERD symptoms; improvements were the greatest for extra-esophageal symptoms in patients with night-time symptoms. Pantoprazole-Mg was well tolerated.

Conclusions: Pantoprazole-Mg 40 mg significantly improved a broad range of esophageal and extra-esophageal GERD related symptoms including sleep disturbances, as well as well-being, in patients with daytime or night-time GERD, making it a good option for patients with GERD, especially when extra-esophageal and night-time symptoms are present.
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http://dx.doi.org/10.5056/jnm.2014.20.1.64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895611PMC
January 2014

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

Tuberculosis (Edinb) 2013 Dec;93 Suppl:S71-7

Texas Biomedical Research Institute, P.O. Box 760549, San Antonio, TX, 78245, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/S1472-9792(13)70014-3DOI Listing
December 2013

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

Rev Esp Enferm Dig 2013 Aug;105(7):392-9

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.
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http://dx.doi.org/10.4321/s1130-01082013000700004DOI Listing
August 2013

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

Support Care Cancer 2013 May 14;21(5):1359-63. Epub 2012 Dec 14.

Servicio de Oncología, Hospital General de México, pabellón 111, Doctor Balmis No.148, Col. Doctores. Del. Cuauhtémoc, 06726, Mexico D. F., Mexico.

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.
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http://dx.doi.org/10.1007/s00520-012-1674-6DOI Listing
May 2013

Proton pump inhibitors in gastroesophageal reflux disease: "a custom-tailored therapeutic regimen".

Rev Esp Enferm Dig 2012 Jul;104(7):367-78

Department of Endoscopy, Hospital Ángeles del Pedregal, Instituto Nacional de Cancerología, Mexico, D.F.

The Montreal Definition and Classification divides Gastroesophageal Reflux Disease (GERD) into esophageal symptomatic syndromes (and with mucosal damage) and extraesophageal syndromes (with acid established association and proposed association). In typical GERD symptoms, an 8-week treatment with PPIs is satisfactory in most cases (> 90%). Response rates to PPIs in GERD are highly variable, as they also rely on an appropriate clinical diagnosis of the disease; endoscopy differentiates the macroscopic GERD phenotype. The non-erosive variety (50-70% prevalence) has a different symptomatic response rate, as gastric acid is not the sole etiology of symptoms. The possible explanations of treatment failure include treatment adherence, PPI metabolism alterations and characteristics, and inadequate diagnosis. Refractory symptoms are related to gastric content neutralization by the chronic use of PPIs.Extraesophageal manifestations are associated with other pathophysiological mechanisms where an autonomic nervous system disturbance gives rise to symptoms. In these clinical entities, the relationship between symptoms and acid needs to be established in order to determine the use of PPIs, or consider other drugs. In other words, so as to "custom-tailor the best-fitting therapy" we need to answer the questions for whom, for what, how and for how long. Finally, PPI safety and tolerability are factors to be considered in elderly patients requiring chronic PPI use, who usually have chronic concomitant illnesses.
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http://dx.doi.org/10.4321/s1130-01082012000700006DOI Listing
July 2012

Integrating genomic analysis with the genetic basis of gene expression: preliminary evidence of the identification of causal genes for cardiovascular and metabolic traits related to nutrition in Mexicans.

Adv Nutr 2012 Jul 1;3(4):596S-604S. Epub 2012 Jul 1.

Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.

Whole-transcriptome expression profiling provides novel phenotypes for analysis of complex traits. Gene expression measurements reflect quantitative variation in transcript-specific messenger RNA levels and represent phenotypes lying close to the action of genes. Understanding the genetic basis of gene expression will provide insight into the processes that connect genotype to clinically significant traits representing a central tenet of system biology. Synchronous in vivo expression profiles of lymphocytes, muscle, and subcutaneous fat were obtained from healthy Mexican men. Most genes were expressed at detectable levels in multiple tissues, and RNA levels were correlated between tissue types. A subset of transcripts with high reliability of expression across tissues (estimated by intraclass correlation coefficients) was enriched for cis-regulated genes, suggesting that proximal sequence variants may influence expression similarly in different cellular environments. This integrative global gene expression profiling approach is proving extremely useful for identifying genes and pathways that contribute to complex clinical traits. Clearly, the coincidence of clinical trait quantitative trait loci and expression quantitative trait loci can help in the prioritization of positional candidate genes. Such data will be crucial for the formal integration of positional and transcriptomic information characterized as genetical genomics.
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http://dx.doi.org/10.3945/an.112.001925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649732PMC
July 2012

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

Am J Gastroenterol 2012 May 24;107(5):747-53. Epub 2012 Jan 24.

Laboratory of Liver, Pancreas and Motility-HIPAM, Department of Experimental Medicine, Faculty of Medicine, Universidad Nacional Autónoma de México-UNAM, México City, México.

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.
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http://dx.doi.org/10.1038/ajg.2011.484DOI Listing
May 2012