Búsqueda de selección en el polimorfismo 677C>T (c.665C>T) del gen de la metilentetrahidrofolato reductasa (MTHFR) en una población Colombiana

Se realizó un estudio genético – poblacional en dos grupos etarios de población colombiana con la finalidad de evaluar las diferencias genéticas relacionadas con el polimorfismo MTHFR 677CT en busca de eventos genéticos que soporten la persistencia de este polimorfismo en la especie humana debido que este ha sido asociado con múltiples enfermedades. De esta manera se genotipificaron los individuos, se analizaron los genotipos, frecuencias alélicas y se realizaron diferentes pruebas genéticas-poblacionales. Contrario a lo observado en poblaciones Colombianas revisadas se identificó la ausencia del Equilibrio Hardy-Weinberg en el grupo de los niños y estructuras poblacionales entre los adultos lo que sugiere diferentes historias demográficas y culturales entre estos dos grupos poblacionales al tiempo, lo que soporta la hipótesis de un evento de selección sobre el polimorfismo en nuestra población. De igual manera nuestros datos fueron analizados junto con estudios previos a nivel nacional y mundial lo cual sustenta que el posible evento selectivo es debido a que el aporte de ácido fólico se ha incrementado durante las últimas dos décadas como consecuencia de las campañas de fortificación de las harinas y suplementación a las embarazadas con ácido fólico, por lo tanto aquí se propone un modelo de selección que se ajusta a los datos encontrados en este trabajo se establece una relación entre los patrones nutricionales de la especie humana a través de la historia que explica las diferencias en frecuencias de este polimorfismo a nivel espacial y temporal.  

Tratamiento de Artritis reumatoide con antagonistas del factor de necrosis tumoral alfa y su asociación con el desarrollo de melanoma cutáneo: revisión sistemática de la literatura y meta-análisis.

Introducción: El tratamiento con antagonistas del factor de necrosis tumoral alfa (anti TNF) ha impactado el pronóstico y la calidad de vida de los pacientes con artritis reumatoide (AR) positivamente, sin embargo, se interroga un incremento en el riesgo de desarrollar melanoma. Objetivo: Conocer la asociación entre el uso de anti TNF y el desarrollo de melanoma maligno en pacientes con AR. Metodología: Se realizó una búsqueda sistemática en MEDLINE, EMBASE, COCHRANE LIBRARY y LILACS para ensayos clínicos, estudios observacionales, revisiones y meta-análisis en pacientes adultos con diagnóstico de AR y manejo con anti TNF (Certolizumab pegol, Adalimumab, Etanercept, Infliximab y Golimumab). Resultados: 37 estudios clínicos cumplieron los criterios de inclusión para el meta-análisis, con una población de 16567 pacientes. El análisis de heterogeneidad no fue significativo (p=1), no se encontró diferencia en el riesgo entre los grupos comparados DR -0.00 (IC 95% -0.001; -0.001). Un análisis adicional de los estudios en los que se reportó al menos 1 caso de melanoma (4222 pacientes) tampoco mostró diferencia en el riesgo DR -0.00 (IC 95% -0.004 ; -0.003). Conclusión: En la evidencia disponible a la fecha no encontramos asociación significativa entre el tratamiento con anti TNF en pacientes con diagnóstico de AR y el desarrollo de melanoma cutáneo.

Caracterizacion de nódulos tiroideos: concordancia entre estudio citopatologico y ecografia en la detección de nódulos malignos

: Los métodos imagenológicos para evaluar los nódulos tiroideos han sido motivo de estudio en las últimas décadas, especialmente la ecografía sobresale sobre las otras modalidades diagnósticas por su accesibilidad, portabilidad, y seguridad. A pesar de ello, las características ecográficas de cada nódulo han sido objeto de controversia en cuanto a su potencial detección de malignidad o benignidad. Se presenta un estudio de concordancia entre el estudio citopatológico y la ecografía para la caracterización nódulos tiroideos de naturaleza maligna y benigna, y su análisis de pruebas diagnósticas. Metodología: Se realizó un estudio descriptivo de concordancia con estudio de pruebas diagnósticas anidado. Se escogieron todos los pacientes con nódulos tiroideos a quienes se les realizó ecografía y estudio citopatológico de la lesión y se estudiaron los hallazgos ecográficos para evaluar su potencial diagnóstico para malignidad. Se incluyeron un total de 100 pacientes con nódulos tiroideos potencialmente malignos. La concordancia entre la ecografía en modo B y el estudio citopatológico fue moderada (índice kappa 0.55). La característica con mayor potencial para detectar malignidad fue la presencia de Microcalcificaciones (sensibilidad 75%, especificidad 92%).

Actitudes hacia el VIH/SIDA, el cáncer y la enfermedad de Alzheimer

Esta revisión de la literatura tuvo como objetivo describir las actitudes hacia el VIH/SIDA, el cáncer y la Enfermedad de Alzheimer desde el modelo tripartito. Se revisaron 109 artículos publicados entre 2005 y 2015 en algunas bases de datos especializadas y herramientas de análisis de impacto. También se incluyeron fuentes secundarias ampliándose la búsqueda a los últimos 20 años (1995-2015). Los resultados mostraron que la mayoría de los estudios realizados sobre las actitudes hacia estas tres enfermedades son de tipo cuantitativo y la información se analizó con base en los componentes del modelo tripartito. Algunos aspectos sociodemográficos como el sexo y la edad están asociados con las actitudes hacia las tres enfermedades y predominan las creencias erróneas sobre ellas respecto a sus causas, curso y tratamiento. También predominan actitudes negativas hacia las tres enfermedades y las conductas e intenciones conductuales son diversas hacia cada una de ellas. No se hallaron antecedentes empíricos del estudio de la estructura de las actitudes propuesta por el modelo tripartito hacia las tres enfermedades. La Salud Pública ha liderado la investigación con base en el modelo de conocimientos, actitudes y prácticas propuesto por la OMS.

Meta-analysis: a unifying meta-likelihood approach framing unobserved heterogeneity, study covariates, publication bias, and study quality

OBJECTIVES: This contribution provides a unifying concept for meta-analysis integrating the handling of unobserved heterogeneity, study covariates, publication bias and study quality. It is important to consider these issues simultaneously to avoid the occurrence of artifacts, and a method for doing so is suggested here. METHODS: The approach is based upon the meta-likelihood in combination with a general linear nonparametric mixed model, which lays the ground for all inferential conclusions suggested here. RESULTS: The concept is illustrated at hand of a meta-analysis investigating the relationship of hormone replacement therapy and breast cancer. The phenomenon of interest has been investigated in many studies for a considerable time and different results were reported. In 1992 a meta-analysis by Sillero-Arenas et al. concluded a small, but significant overall effect of 1.06 on the relative risk scale. Using the meta-likelihood approach it is demonstrated here that this meta-analysis is due to considerable unobserved heterogeneity. Furthermore, it is shown that new methods are available to model this heterogeneity successfully. It is argued further to include available study covariates to explain this heterogeneity in the meta-analysis at hand. CONCLUSIONS: The topic of HRT and breast cancer has again very recently become an issue of public debate, when results of a large trial investigating the health effects of hormone replacement therapy were published indicating an increased risk for breast cancer (risk ratio of 1.26). Using an adequate regression model in the previously published meta-analysis an adjusted estimate of effect of 1.14 can be given which is considerably higher than the one published in the meta-analysis of Sillero-Arenas et al. In summary, it is hoped that the method suggested here contributes further to a good meta-analytic practice in public health and clinical disciplines.

Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay

The mapping of genes which affect individual cancer risk is an important but complex challenge. A surrogate assay of susceptibility to radiation-induced acute myeloid leukaemia (AML) in the mouse based on chromosomal radiosensitivity has been developed and validated. This assay was applied to the mapping of radiation-induced AML risk modifier loci by association with microsatellite markers. A region on chromosome (chr) 18 with strong association is identified and confirmed by backcross analysis. Additional loci on chrs 8 and 13 show significant association. A key candidate gene Rbbp8 on chr18 is identified. Rbbp8 is shown to be upregulated in response to X-irradiation in the AML sensitive CBA strain but not AML resistant C57BL/6 strain. This study demonstrates the strength of utilizing surrogate endpoints of cancer susceptibility in the mapping of mouse loci and identifies additional loci that may affect radiation cancer risk.

Selected topics in probiotics and prebiotics: meeting report for the 2004 international scientific association for probiotics and prebiotics

On August 2931, 2004, 84 academic and industry scientists from 16 countries gathered in Copper Mountain, Colorado USA to discuss certain issues at the forefront of the science of probiotics and prebiotics. The format for this invitation only meeting included six featured lectures: engineering human vaginal lactobacilli to express HIV inhibitory molecules (Peter Lee, Stanford University), programming the gut for health (Thaddeus Stappenbeck, Washington University School of Medicine), immune modulation by intestinal helminthes (Joel Weinstock, University of Iowa Hospitals and Clinics), hygiene as a cause of autoimmune disorders (G. A. Rook, University College London), prebiotics and bone health (Connie Weaver, Purdue University) and prebiotics and colorectal cancer risk (Ian Rowland, Northern Ireland Centre for Food and Health). In addition, all participants were included in one of eight discussion groups on the topics of engineered probiotics, host-commensal bacteria communication, 'omics' technologies, hygiene and immune regulation, biomarkers for healthy people, prebiotic and probiotic applications to companion animals, development of a probiotic dossier, and physiological relevance of prebiotic activity. Brief conclusions from these discussion groups are summarized in this paper.

Modulation of detoxification enzymes by watercress: in vitro and in vivo investigations in human peripheral blood cells

Epidemiological studies indicate that consumption of cruciferous vegetables (CV) can reduce the risk of cancer. Supposed mechanisms are partly the inhibition of phase I and the induction of phase II enzymes. The aim of this study was to investigate in vitro and in vivo effects of watercress (WC), a member of the CV family, on chemopreventive parameters using human peripheral blood mononuclear cells (PBMC) as surrogate cells. We investigated the hypothesis that WC reduces cancer risk by inducing detoxification enzymes in a genotype-dependent manner. In vitro gene expression and enzyme activity experiments used PBMC incubated with a crude extract from fresh watercress (WCE, 0.1-10 mu L/mL with 8.2 g WC per 1 mL extract) or with one main key compound phenethyl isothiocyanate (PEITC, 1-10 mu M). From an in vivo perspective, gene expression and glutathione S-transferase (GST) polymorphisms were determined in PBMC obtained from a human intervention study in which subjects consumed 85 g WC per day for 8 weeks. The influence of WC consumption on gene expression was determined for detoxification enzymes such as superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPX1), whilst the SOD and GPX activities in red blood cells were also analysed with respect to GST genotypes. In vitro exposure of PBMC to WCE or PEITC (24 h) increased gene expression for both detoxification enzymes GPX1 (5.5-fold, 1 mu L/mL WCE, 3.7-fold 1 mu M PEITC) and SOD2 (12.1-fold, 10 mu L/mL WCE, 7.3-fold, 10 mu M PEITC), and increased SOD2 activity (1.9-fold, 10 mu L/mL WCE). The WC intervention had no significant effect on in vivo PBMC gene expression, as high individual variations were observed. However, a small but significant increase in GPX (p = 0.025) and SOD enzyme activity (p = 0.054) in red blood cells was observed in GSTM1*0, but not in GSTM1*1 individuals, whilst the GSTT1 genotype had no impact. The results indicate that WC is able to modulate the enzymes SOD and GPX in blood cells in vitro and in vivo, and suggest that the capacity of moderate intake of CV to induce detoxification is dependent in part on the GSTM1 genotype.

Watercress supplementation in diet reduces lymphocyte DNA damage and alters blood antioxidant status in healthy adults

Background: Cruciferous vegetable (CV) consumption is associated with a reduced risk of several cancers in epidemiologic studies. Objective: The aim of this study was to determine the effects of watercress (a CV) supplementation on biomarkers related to cancer risk in healthy adults. Design: A single-blind, randomized, crossover study was conducted in 30 men and 30 women (30 smokers and 30 nonsmokers) with a mean age of 33 y (range: 19-55 y). The subjects were fed 85 g raw watercress daily for 8 wk in addition to their habitual diet. The effect of supplementation was measured on a range of endpoints, including DNA damage in lymphocytes (with the comet assay), activity of detoxifying enzymes (glutathione peroxidase and superoxide dismutase) in erythrocytes, plasma antioxidants (retinol, ascorbic acid, a-tocopherol, lutein, and beta-carotene), plasma total antioxidant status with the use of the ferric reducing ability of plasma assay, and plasma lipid profile. Results: Watercress supplementation (active compared with control phase) was associated with reductions in basal DNA damage (by 17%; P = 0.03), in basal plus oxidative purine DNA damage (by 23.9%; P = 0.002), and in basal DNA damage in response to ex vivo hydrogen peroxide challenge (by 9.4%; P = 0.07). Beneficial changes seen after watercress intervention were greater and more significant in smokers than in nonsmokers. Plasma lutein and P-carotene increased significantly by 100% and 33% (P < 0.001), respectively, after watercress supplementation. Conclusion: The results support the theory that consumption of watercress can be linked to a reduced risk of cancer via decreased damage to DNA and possible modulation of antioxidant status by increasing carotenoid concentrations.

Effect of processed and red meat on endogenous nitrosation and DNA damage

Haem in red meat (RM) stimulates the endogenous production of mutagenic nitroso compounds (NOC). Processed (nitrite-preserved red) meat additionally contains high concentrations of preformed NOC. In two studies, of a fresh RM versus a vegetarian (VEG) diet (six males and six females) and of a nitrite-preserved red meat (PM) versus a VEG diet (5 males and 11 females), we investigated whether processing of meat might increase colorectal cancer risk by stimulating nitrosation and DNA damage. Meat diets contained 420 g (males) or 366 g (females) meat/per day. Faecal homogenates from day 10 onwards were analysed for haem and NOC and asso- ciated supernatants for genotoxicity. Means are adjusted for differ- ences in male to female ratios between studies. Faecal NOC concentrations on VEG diets were low (2.6 and 3.5 mmol/g) but significantly higher on meat diets (PM 175 ± 19 nmol/g versus RM 185 ± 22 nmol/g; P 5 0.75). The RM diet resulted in a larger pro- portion of nitrosyl iron (RM 78% versus PM 54%; P < 0.0001) and less nitrosothiols (RM 12% versus PM 19%; P < 0.01) and other NOC (RM 10% versus PM 27%; P < 0.0001). There was no statis- tically significant difference in DNA breaks induced by faecal water (FW) following PM and RM diets (P 5 0.80). However, PM re- sulted in higher levels of oxidized pyrimidines (P < 0.05). Surpris- ingly, VEG diets resulted in significantly more FW-induced DNA strand breaks than the meat diets (P < 0.05), which needs to be clarified in further studies. Meats cured with nitrite have the same effect as fresh RM on endogenous nitrosation but show increased FW-induced oxidative DNA damage.

MYOD-1 in normal colonic mucosa - role as a putative biomarker?

Background DNA methylation of promoter-associated CpG islands of certain genes may play a role in the development of colorectal cancer. The MYOD-1 gene which is a muscle differentiation gene has been showed to be significantly methylated in colorectal cancer which, is an age related event. However the role of this gene in the colonic mucosa is not understood and whether methylation occurs in subjects without colon cancer. In this study, we have determined the frequency of methylation of the MYOD-1 gene in normal colonic mucosa and investigated to see if this is associated with established colorectal cancer risk factors primarily ageing. Results We analysed colonic mucosal biopsies in 218 normal individuals and demonstrated that in most individuals promoter hypermethylation was not quantified for MYOD-1. However, promoter hypermethylation increased significantly with age (p < 0.001 using regression analysis) and this was gender independent. We also showed that gene promoter methylation increased positively with an increase in waist to hip (WHR) ratio - the latter is also a known risk factor for colon cancer development. Conclusions Our study suggests that promoter gene hypermethylation of the MYOD-1 gene increases significantly with age in normal individuals and thus may offer potential as a putative biomarker for colorectal cancer.

Geographical variation in total and inorganic arsenic content of polished (white) rice

An extensive data set of total arsenic analysis for 901 polished (white) grain samples, originating from 10 countries from 4 continents, was compiled. The samples represented the baseline (i.e., not specifically collected from arsenic contaminated areas), and all were for market sale in major conurbations. Median total arsenic contents of rice varied 7-fold, with Egypt (0.04 mg/kg) and India (0.07 mg/kg) having the lowest arsenic content while the U.S. (0.25 mg/kg) and France (0.28 mg/kg) had the highest content. Global distribution of total arsenic in rice was modeled by weighting each country’s arsenic distribution by that country’s contribution to global production. A subset of 63 samples from Bangladesh, China, India, Italy, and the U.S. was analyzed for arsenic species. The relationship between inorganic arsenic content versus total arsenic content significantly differed among countries, with Bangladesh and India having the steepest slope in linear regression, and the U.S. having the shallowest slope. Using country-specific rice consumption data, daily intake of inorganic arsenic was estimated and the associated internal cancer risk was calculated using the U.S. Environmental Protection Agency (EPA) cancer slope. Median excess internal cancer risks posed by inorganic arsenic ranged 30-fold for the 5 countries examined, being 0.7 per 10,000 for Italians to 22 per 10,000 for Bangladeshis, when a 60 kg person was considered.

Impact of palm date consumption on microbiota growth and large intestinal health: a randomised, controlled, cross-over, human intervention study

The reported inverse association between the intake of plant-based foods and a reduction in the prevalence of colorectal cancer may be partly mediated by interactions between insoluble fibre and (poly)phenols and the intestinal microbiota. In the present study, we assessed the impact of palm date consumption, rich in both polyphenols and fibre, on the growth of colonic microbiota and markers of colon cancer risk in a randomised, controlled, cross-over human intervention study. A total of twenty-two healthy human volunteers were randomly assigned to either a control group (maltodextrin-dextrose, 37·1 g) or an intervention group (seven dates, approximately 50 g). Each arm was of 21 d duration and was separated by a 14-d washout period in a cross-over manner. Changes in the growth of microbiota were assessed by fluorescence in situ hybridisation analysis, whereas SCFA levels were assessed using HPLC. Further, ammonia concentrations, faecal water genotoxicity and anti-proliferation ability were also assessed using different assays, which included cell work and the Comet assay. Accordingly, dietary intakes, anthropometric measurements and bowel movement assessment were also carried out. Although the consumption of dates did not induce significant changes in the growth of select bacterial groups or SCFA, there were significant increases in bowel movements and stool frequency (P<0·01; n 21) and significant reductions in stool ammonia concentration (P<0·05; n 21) after consumption of dates, relative to baseline. Furthermore, date fruit intake significantly reduced genotoxicity in human faecal water relative to control (P<0·01; n 21). Our data indicate that consumption of date fruit may reduce colon cancer risk without inducing changes in the microbiota.

Recurrent sores by ill-fitting dentures and intra-oral squamous cell carcinoma in smokers

Objectives: To examine whether denture use and recurrent sores caused by ill-fitting dentures are associated with intra-oral squamous cell carcinoma (IO-SCC) in individuals exposed to tobacco. Methods: We conducted a hospital-based case-control study. The study population comprised 124 patients with IO-SCC and the same number of controls (individually paired according to gender and age) recruited from outpatient units of the same hospital. Conditional logistic regression analysis assessed the effect of denture use and recurrent oral sores by ill-fitting dentures, adjusted by covariates on the lifetime exposure to alcohol and tobacco, socioeconomic standings, and dietary patterns. Results: The use of dentures showed no association with IO-SCC [adjusted odds ratio (OR) 1.40, 95 percent confidence interval 0.51-3.87, P = 0.513] in an assessment controlled by socioeconomic position, lifetime exposure to alcohol and tobacco, and dietary patterns. However, the report of recurrent sores caused by ill-fitting dentures showed significant association with the disease (adjusted OR 4.58, 95 percent confidence interval 1.52-13.76, P = 0.007). Conclusions: The association between recurrent oral sores caused by ill-fitting dentures and squamous cell carcinoma of the mouth in smokers is in agreement with the hypothesis that the chronic physical irritation of oral mucosa contributes to the topical carcinogenic effect of tobacco, which must be taken into careful consideration in the planning of dental services for adults and the elderly.

Patterns of Antibodies Against Latent and Lytic Antigens of Human Herpesvirus 8 in an Endemic Population and Patients With Kaposi`s Sarcoma in Mozambique

The patterns of antibodies against latent and lytic antigens of human herpesvirus 8 (HHV-8) were assessed using immunofluorescence assays of samples from 155 persons seropositive for HHV-8 seen at public health centers and 24 patients with Kaposi`s sarcoma (KS) from Mozambique. Of the 155 persons without KS, 48(31%) had antibodies against latent antigens only, 29 (18.7%) had antibodies against lytic antigens only, and 78 (50.3%) had antibodies against both types of antigen. The HHV-8 antibody titer tended to increase with age until age 40, after which it began to decrease. High titers of antibodies against latent and lytic antigens of HHV-8 were detected mostly in persons co-infected with HIV, and these increased titers could have a predictive value. All patients with KS except four patients who were seronegative for HHV-8 had elevated titers of HHV-8 antibodies, predominantly against latent antigens. The data suggest the potential for an increase in the development of KS in this endemic area for HHV-8. J. Med. Virol. 82:1576-1581, 2010. (C) 2010 Wiley-Liss, Inc.