Medicina molecular y genética

XRCC3 Thr241Met polymorphism has been associated with cancer susceptibility. Studies have shown a relationship between Thr241Met polymorphism and gastric cancer. The present study was aimed at examining the presence of XRCC3 Thr241Met polymorphism in patients diagnosed with gastric cancer in the city of Macapá. We analyzed 150 DNA samples, of which 100 comprised the control group and 50 were case patients. Our findings revealed that 76% of case samples had the Thr/Met genotype (OR (CI 95% 54.29 (18.84-156.38) p ≤ 0.0001) whereas in the control group, the same genotype represented 7%. Also, most gastric cancer patients with XRCC3 241Met polymorphism were heterozygotes. Given the small sample size in this study, a larger number of patients will be analyzed.

Introduction: Asthma exacerbations are associated with viral upper respiratory tract infections, and rhinovirus (RV) is the major cause of these virus-associated exacerbation. Circadian clocks regulate physiological rhythms via transcriptional networks. These networks contain several feedback mechanisms inducing complex tissue specific patterns of gene activation and repression that help to maintain and regulate important biological processes. For example, the neutrophil inflammation of the lung is gated by epithelial circadian oscillators. We hypothesized that recurrent, human rhinovirus infection (HRVI) of in in vitro cultured cells alter the circadian-gated inflammatory networks and imprint a methylation pattern similar to the network found in asthmatic patients.

Results: We measured the methylation of clock and inflammatory genes in the BEAS2-B cell line after 1, 3 or 5 consecutive rhinovirus infections. Hierarchical clustering of methylation levels identified distinct clusters of numbers of infection (NOI: 1,3 and 5) for clock and inflammatory genes in BEAS2-B cells. Furthermore, a linear regression model of the methylation level was used to identify significantly increased or decreased loci (p<0.01). In non-infected cells, clear clusters of RNA expression of circadian clock genes CRY1, PER2, PER3, CLOCK were found to be negatively associated with interleukin 8 (IL-8) expression. After HRVI a partial reversal is observed and the expression of the CLOCK gene is positively correlated to IL-8 expression Similarly, in asthmatic patients, a strong positive correlation between CLOCK and IL-8 was found.

Conclusion: This study provides first insights in how repeated viral infections (e.g. HRVI exacerbations in asthma) may introduce persistent changes to circadian-gated inflammatory networks involved in governing neutrophil recruitment. This could offer novel diagnostic strategies to identify and define certain asthmatic endotypes and lead to novel therapeutic approaches based on circadian rhythm stabilization.

To date, there are no efficient treatments for most of human congenital, developmental, or degenerative diseases because functional cells failed to regenerate new cells following damages to original cells. Stem Cell (SC) based therapeutic approach holds tremendous promise for treating these abnormalities by replacing the damaged cells. This approach has sparked unprecedented attention in this field. However, SC researchers should adopt more robust techniques that incorporate marker genes that render stem cells visible using fluorescence and conventional microscopy. We design a unique approach to label embryonic and adult stem cells, the peptide-mediated quantum dots (QDs) SCs labeling with plasmalemma and nucleolemma specific fusion peptides. Therefore, the targeted SCs will be distinguishable by the new markers to report grafted cells from endogenous cardiomyocytes and to display the trans-differentiation from the SCs. The fluorescence strength of nanocrystal QDs will surmount the interference of the false signals originating from auto-fluorescence of cardiac tissues with their features for anti-bleaching of nonorganic dye.

With the advancement in technology, compositional analysis of saliva for diagnosis of various medical conditions has attracted the researchers over the last decade. Monitoring the salivary biomarkers help in early detection of diseases and increase the rate of success of the treatment. Sampling of saliva is safe, simple, cost effective and does not demand an expertise for collection. Therefore, saliva can be an important diagnostic armamentarium for mass screening for a specific disease or in remote areas. However, despite of various research, there are no definite guidelines regarding sensitivity and specificity of salivary diagnostic tools. Health care professionals must go hand in hand with government agencies to develop more research so that a general acceptance can be developed like that of traditional blood/urine analysis.

In a previous case study, four patients at different stages of Parkinson’s disease (PD) and Neurocognitive Disorder with Lewy Bodies (NCDLB) disease progression were treated with Donepezil, with the intention of mitigating Lewy body impairment of the cholinergic pathways in the myenteric plexus, increasing bowel motility, and reducing the symptom of constipation. In all four cases, the use of Donepezil was associated with significant reduction of the symptom of constipation. There was no exacerbation or instigation of other symptoms. The symptom status of the four patients was reviewed six months later. In none of the patients has there been exacerbation of the symptom of constipation, nor emergence of new symptoms. The findings suggest that Donepezil might have long-term efficacy for reducing constipation in patients with PD and NCDLB. Further research is recommended using larger numbers of subjects matched for diagnosis, age, gender, and other variables.

Objective: The aim of this study is to investigate the prevalence of sensori-neural hearing loss and ototoxicity in acute myeloid leukemia (AML) patients.

Study design: This is a prospective non-randomized study.

Methods: 14 patients with the diagnosis of acute myeloid leukemia were treated with Daunorubicin and Cytarabine (ARA-C). Pure Tone Audiometry (PTA) was performed prior to induction chemotherapy and immediately after completion of induction protocol. Primary outcome was the prevalence of sensori-neural hearing loss. Secondary outcome was correlation of age, sex, absolute neutrophil counts, total white counts, platelet counts and creatinine levels in the study population.

Results: Fourteen patients participated in this study (n=14). Ten patients had normal hearing prior to preinduction treatment. Four patients had pre-existing hearing loss prior to treatment. Post induction treatment, ten patients had normal hearing. However, from these ten patients, one had pre-existing hearing loss which improved. Two patients, whom had normal hearing and pre-existing hearing loss pre-induction treatment respectively, expired. Two patients who had pre-existing hearing loss had the same level of hearing post induction. The prevalence of sensori-neural hearing loss in this study is 71.4%. From our observation, there is no evidence of ototoxicity from induction therapy of Daunorubicin and Cytarabine (ARA-C) in our study population (p=0.001). Induction treatment with Daunorubicin and Cytarabine (ARA-C) shows statistically significant reduction in Absolute Neutrophils Counts (p=0.013), Total White Counts (p=0.001), Haemoglobin Counts (p=0.036) and Creatinine levels (p=0.017) in our study population. Even though Platelet counts showed reduction, this was not supported statistically (p=0.258).

Conclusion: Induction treatment with Daunorubicin and Cytarabine (ARA-C) are safe chemotherapy agents to be administered during the induction phase in treatment of Acute Myeloid Leukemia with no evidence of sensorineural hearing loss. Further study is required to monitor the long-term effects of these drugs during consolidation, remission or relapse phases of treatment and if possible during stem cell transplant treatment.

Deciphering human genome has ushered modern bio-medical science towards a future hope of revitalizing current symptomatic or prophylactic treatment methods into personalized and predictive medicine depending upon an individual’s genetic makeup. Genetic variations related to a person’s response towards drugs, differential susceptibility to disease and reciprocity of phenotypic attributes related to environment, ethno-racial origin and diseases to genotypes have not been meticulously apprehended yet. Ayurveda, an age-old health science resonated unequivocally with ancient system of classifying a person on the basis of “Prakriti” or unchangeable constitution type might be an advantageous inclination towards personalized medicine, bearing testable molecular and genetic correlates. Several genomic and metabolomic studies augmented the possibilities of yet undisclosed molecular and genetic basis of Ayurveda, which could further be integrated or complemented to current medical diagnosis and treatment. Further deep dive into the extremes of utilizable science and technology of this holistic practice remained quintessential for better enlightenment of future bio-medical science to fight all fiends of ailments.

Epidermal growth factor receptor (EGFR) is a member of the EGFR tyrosine kinase family, which consists of EGFR (erbB1/Her1), Her2/neu (erbB2), Her3 (erbB3) and Her4 (erbB4). HER receptors are ubiquitously expressed in various cell types, under homeostatic conditions, receptor activation is tightly regulated by the availability of ligands, which collectively form the EGF family.

Purpose: 18F-fluorodeoxyglucose (¹⁸F-FDG) accumulation in the left ventricular (LV) wall detects active myocardial inflammatory lesions in cardiac sarcoidosis (CS), but the significance of ¹⁸F-FDG accumulation in mediastinal and hilar lymph nodes (LNs) remains unclear. We investigated the association between CS recurrence and ¹⁸F-FDG accumulation in the mediastinal and hilar LNs, using positron emission tomography/computed tomography (PET/CT).

Materials and Methods: We retrospectively analyzed the records of 68 patients diagnosed with CS, who underwent ¹⁸F-FDG PET/CT before beginning treatment. The minimum follow-up period was 24 months. Patients were assigned to the recurrence (n=18) or no recurrence group (n=50) based on follow-up examinations. The 18FFDG PET/CT maximum standardized uptake value (SUV_max) was measured in the LV wall, right ventricular (RV) wall, and mediastinal and hilar LNs. The association of CS recurrence was analyzed using Cox proportional hazards models. Recurrence-free survival (RFS) curves were made using the Kaplan-Meier method.

Results: In univariate analysis, sex, BNP, LVEF, and the SUV_max in the LV wall, RV wall, and mediastinal and hilar LNs were significant risk factors for CS recurrence. In multivariate analysis, only the SUV_max in the mediastinal and hilar LNs was a significant risk factor for CS recurrence. RFS rates were significantly higher in patients with an SUV_max<4.1 vs. ≥ 4.1 (log-rank value=36.0, p<0.01).

Conclusion: The mediastinal and hilar LN SUV_max was an independent risk factor for CS recurrence after treatment. ¹⁸F-FDG accumulation in mediastinal and hilar LNs on ¹⁸F-FDG PET before treatment may be a useful biomarker to predict CS recurrence.

Este informe de caso tuvo como objetivo caracterizar las anomalías dentoóseas en la poliposis adenomatosa familiar (PAF) en un paciente brasileño. Además, se investigó la PAF como posible causa. Este informe de caso mostró la importancia del conocimiento dentoóseo relacionado con la PAF. El diagnóstico temprano de anomalías dentoóseas reveló la necesidad de realizar un seguimiento de los miembros de la familia con PAF desde la infancia y fue esencial para el diagnóstico posterior de PAF clínico o genético. Los autores creen que este trabajo es importante ya que brinda información destacada sobre el papel del dentista en el diagnóstico temprano de la PAF, una enfermedad que predispone al cáncer colorrectal.

La hemooxigenasa-1 ( HO-1 ) es importante en la defensa contra el estrés oxidativo. Los polimorfismos de longitud en esta región de repetición GT se correlacionan con los niveles de expresión de HO-1 y se asocian con varias enfermedades. El objetivo de este estudio fue probar la posible asociación de HO-1 (número de repeticiones GT) con los niveles de metahemoglobina en la metahemoglobinemia congénita recesiva en la población india. Se realizó la genotipificación del ADN aislado de la sangre completa de 25 pacientes con RCM debido a la deficiencia de NADH citocromo b5 reductasa y 50 controles sanos. El análisis del tamaño de los fragmentos por secuenciación se utiliza para la definición de genotipo/alelo mediante el analizador genético ABI 3130 y el tamaño del producto de PCR se calcula mediante el software Gene Mapper. La importancia de los hallazgos se probó utilizando la prueba χ(2). Los polimorfismos HO-1 (número de repeticiones GT) se asociaron significativamente con RCM. Los resultados del análisis de genotipado indicaron que un genotipo que lleva alelos cortos (<24 repeticiones (GT)n se prefieren preferentemente con pacientes con RCM que en el control (P <0,001). El genotipo de alelo corto (<24 repeticiones GT) estuvo presente en el 82% del grupo de pacientes con metahemoglobinemia y el alelo largo (≥31 repeticiones GT) se inspecciona en el grupo de control normal. polimorfismo HO-1 (número de repeticiones GT) y RCM Las frecuencias de alelos y genotipos para los polimorfismos HO-1 muestran una asociación significativa con la gravedad de la enfermedad. Estos datos también podrían ser valiosos para los médicos, principalmente los hematólogos. al intentar un diagnóstico definitivo de la causa de la metahemoglobinemia que ayudará a las decisiones clínicas para el tratamiento.

La enfermedad de Rosai Dorfman, también conocida como histiocitosis con linfadenopatía masiva, es una enfermedad idiopática muy poco frecuente. Se caracteriza por la sobreproducción y acumulación de histiocitos sinusales de Langerhans, con mayor frecuencia en los ganglios linfáticos, pero puede presentarse en otras áreas y provocar daño orgánico. Según las investigaciones, puede ser causado por un agente infeccioso, inmunodeficiencia o autoinmunidad y causas genéticas. La manifestación extranodal es poco común; Sin embargo, los sitios extranodales incluyen hígado, riñón, órganos respiratorios, órbita y globo ocular. Presentamos un informe de caso de una mujer de 44 años con infiltración orbitaria bilateral recurrente como primera ubicación de la enfermedad de Rosai Dorfman.

Los secuestros pulmonares (SP) son masas de tejido pulmonar no funcionales. La mayoría de los SP se encuentran en la cavidad torácica; muy raramente se encuentran debajo del diafragma, en particular en la zona suprarrenal izquierda. Una primigrávida de 33 años se sometió a una ecografía a las 24+2 semanas de gestación. La ecografía mostró una masa hiperecogénica situada debajo del diafragma. La ecografía Doppler color mostró que los vasos que irrigaban la masa se originaban en la aorta abdominal. El feto fue diagnosticado preliminarmente con SP infradiafragmático. La paciente optó por interrumpir el embarazo. Se sometió a odinopeia para dar a luz a un feto masculino que se sometió a un examen post mortem que confirmó las anomalías diagnosticadas prenatalmente.

Objetivo: Investigar el grado de cualquier efecto decreciente del riesgo relativo excesivo (ERR) de exposición a la radiación causada por el ajuste por tabaquismo y años de educación.

Métodos: En este estudio de cohorte, reunimos una cohorte de 41.742 hombres que respondieron a una encuesta sobre estilo de vida realizada en 2003 y que estaban registrados en el Registro de Dosis de Radiación como trabajadores nucleares japoneses a multas de marzo de 1999. Hubo un total de 215.000 personas-año, mientras que el número de muertes por todos los cánceres, excluida la leucemia, fue de 978. Se utilizó la regresión de Poisson para cuantificar la ERR por Sv y se realizó una comparación de las ERR antes del ajuste por tabaquismo o años de educación y después de esos ajustes.

Resultados: Para todos los cánceres, excepto la leucemia, la ERR/Sv fue de 0,78 (IC del 90 %: -0,65, 2,20). Sin embargo, disminuyó a 0,31 (-1,03, 1,65) cuando se ajustó por tabaquismo ya 0,42 (-0,94, 1,79) cuando se ajustó por años de educación. Al ajustar tanto por tabaquismo como por años de educación, disminuyó a 0,08 (-1,22, 1,39).

Conclusión: Nuestros resultados demuestran la importancia de recopilar datos sobre el estilo de vida y ajustarlos al estimar el riesgo de radiación.

El cáncer colorrectal (CCR) representa una amenaza grave para la salud de las poblaciones mundiales. La detección temprana del CCR es importante para mejorar la supervivencia del paciente. Los microARN circulantes (miARN, miR), como marcadores de ácidos nucleicos, desempeñan una variedad de funciones importantes en la detección temprana, el diagnóstico, el estadio TNM y los pronósticos del CCR. En esta revisión, se presenta una descripción general de las investigaciones recientes sobre las funciones de los miARN circulantes y sus posibles valores correlacionados con el CCR. Los estudios sobre los valores de los marcadores detectables de los miARN circulantes para el CCR ayudarán a lograr un consenso global sobre los procedimientos y protocolos estandarizados para que su transformación clínica sea más confiable.