Expresión génica de mediadores moleculares para potencial terapia celular en el síndrome gastrointestinal inducido por radiación / Genetic expression of molecular mediators for potential cell therapy in radiation-induced gastrointestinal syndrome

Antecedentes: Las células madres intestinales generan las distintas estirpes celulares a dicho nivel. Estas se regulan por interacciones entre el epitelio y las células del nicho celular anexo. Estas se pueden ver dañadas en tratamientos con radiación, generando el síndrome gastrointestinal inducido por radiación. Se ha visto que células madre mesenquimales (MSC) y macrófagos de médula ósea (BMM) tienen propiedades de regeneración tisular. Objetivos: Evaluar la expresión génica de IL-4, Wnt6, VEGF y bFGF, a partir de cultivos celulares primarios independientes de MSC derivadas de tejido adiposo y BMM de ratones C57BL/6, por medio de PCR en tiempo real (qRT-PCR). Diseño experimental: A partir de un análisis in silico, se confeccionaron primers para evaluar la expresión génica de las moléculas propuestas, en los cultivos primarios por medio de qRT-PCR y electroforesis. Resultados y proyecciones: IL-4 y Wnt6 no son expresadas en las muestras de BMM y MSC. VEGF y bFGF son expresadas por diferentes células, dando expresión diferenciada. A futuro, se deben evaluar las mismas estirpes celulares en un ambiente inflamatorio y su efecto en la expresión génica, en especial VEGF y bFGF. Limitaciones: El número de moléculas en estudio es limitado y la expresión se evalúo solo a nivel genético.

Background: Intestinal stem cell generates diferents cellular types in their niche. They're regulated by interactions between epithelium and niche's cells, and can be damaged by medical radiation treatments causing radiation-induced gastrointestinal syndrome. It has seen that mesenchymal stem cells (MSC) d and bone marrow-derived macrophages (BMM) have propierties of tissular regeneration. Objectives: Determinated genetic expression of IL-4, Wnt6, VEGF and bFGF, in primary cellular cultures of MSC derivated of adipose tissue and BMM of C57BL/6 mice, through real time PCR (qRT-PCR). Methods: By an in silico analysis, we created primers to evaluate the proposed molecules in the primary cellular cultives, with qRT-PCR and electrophoresis. Results and projections: IL-4 and Wnt6 were not expressed in the MSC and BMM samples. VEGF and bFGF were expressed by different cells, giving differential expression. In the future, the same samples should be analyzed in an inflammatory environment, especially VEGF and bFGF. Limitations: The number of molecules are limited and the expression of them is only in a genetic level.

Reconstructive dosimetry for cutaneous radiation syndrome

According to the International Atomic Energy Agency (IAEA), a relatively significant number of radiological accidents have occurred in recent years mainly because of the practices referred to as potentially high-risk activities, such as radiotherapy, large irradiators and industrial radiography, especially in gammagraphy assays. In some instances, severe injuries have occurred in exposed persons due to high radiation doses. In industrial radiography, 80 cases involving a total of 120 radiation workers, 110 members of the public including 12 deaths have been recorded up to 2014. Radiological accidents in industrial practices in Brazil have mainly resulted in development of cutaneous radiation syndrome (CRS) in hands and fingers. Brazilian data include 5 serious cases related to industrial gammagraphy, affecting 7 radiation workers and 19 members of the public; however, none of them were fatal. Some methods of reconstructive dosimetry have been used to estimate the radiation dose to assist in prescribing medical treatment. The type and development of cutaneous manifestations in the exposed areas of a person is the first achievable gross dose estimation. This review article presents the state-of-the-art reconstructive dosimetry methods enabling estimation of local radiation doses and provides guidelines for medical handling of the exposed individuals. The review also presents the Chilean and Brazilian radiological accident cases to highlight the importance of reconstructive dosimetry.

Radiation injury to the normal brain measured by 3D-echo-planar spectroscopic imaging and diffusion tensor imaging: initial experience.

BACKGROUND AND PURPOSE: Whole brain radiation therapy (WBRT) may cause cognitive and neuropsychological impairment and hence objective assessment of adverse effects of radiation may be valuable to plan therapy. The purpose of our study was to determine the potential of echo planar spectroscopic imaging (EPSI) and diffusion tensor imaging (DTI) in detecting subacute radiation induced injury to the normal brain. MATERIALS AND METHODS: Four patients with brain metastases and three patients with lung cancer underwent cranial irradiation. These patients were subjected to 3D-EPSI and DTI at two time points (pre-radiation, and 1 month post-irradiation). Parametric maps of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), mean diffusivity (MD), and fractional anisotropy (FA) were generated and co-registered to post-contrast T1-weighted images. Normal appearing gray-matter and white-matter regions were compared between the two time points to assess sub-acute effects of radiation using independent sample t-tests. RESULTS: Significantly increased MD (P = .02), Cho/Cr (P = .02) and a trend towards a decrease in NAA/Cr (P = .06) was observed from the hippocampus. Significant decrease in FA (P = .02) from the centrum-semiovale and a significant increase in MD (P = .04) and Cho/Cr (P = .02) from genu of corpus-callosum was also observed. CONCLUSIONS: Our preliminary findings suggest that 3D-EPSI and DTI may provide quantitative measures of radiation induced injury to the normal brain.

Proteins and liver function changes in rats following cumulative total body irradiations / Proteínas y cambios de función hepática en ratas tras irradiación corporal total cumulativa

OBJECTIVE: Total body irradiation (TBI) is a choice therapy for the management of some malignancies; it is also a major cause of oxidative stress. The aim of this research is to sequentially document the effect of total body radiation on body function utilizing the sequential changes in liver function enzymes and proteins in rats. METHODS: Serum protein and liver enzymes were assessed using kits in rats exposed to total body radiations of 1.27 Gy/minute in cumulative doses to the fourth radiation at five-day intervals. RESULTS: Aspartate aminotransferase (AST), alanine transaminase (ALT) and serum protein were significantly (p < 0.05) elevated with increasing radiation. No significant differences between experimental and control groups for bilirubin concentrations were noted at any time. Serum levels of albumin were significantly (p < 0.05) increased with the first to third radiation exposures but reduced at the fourth cumulative dose exposure. CONCLUSION: Variations are associated with acute stress, inflammation which could be due to non-specific stress reaction, while fluctuations could arise as a result of tolerance and repair within the liver. These tests are significant for diagnosis of radiation-induced injury and can be important for evaluation of its severity and correct management.

OBJETIVO: La irradiación corporal total (ICT) es una terapia de elección para el tratamiento de algunos tumores malignos. También es una de las causas principales del estrés oxidativo. El objetivo de esta investigación es documentar el efecto de la radiación corporal total sobre las funciones corporales utilizando los cambios secuenciales en las enzimas de la función hepática y las proteínas en las ratas. MÉTODOS: Se evaluaron las proteínas séricas así como las enzimas hepáticas mediante el uso de kits en ratas expuestas a radiaciones corporales totales de 1.27 Gy/minuto en dosis cumulativas hasta la cuarta radiación con cinco días de intervalo. RESULTADOS: La aspartato transaminasa (AST), la alanina aminotransferasa (ALT) y la proteína sérica fueron elevadas significativamente (p < 0.05) con el aumento creciente de la radiación. No hubo diferencias significativas entre el grupo experimental y el grupo control, observándose concentraciones de bilirrubina todo el tiempo. Los niveles séricos de albúmina aumentaron significativamente (p < 0.05) con la primera de tres exposiciones a la radiación, pero experimentaron una reducción a partir de la cuarta exposición de dosis cumulativa. CONCLUSIÓN: Las variaciones están asociadas con estrés agudo e inflamación que podría deberse a una reacción a estrés no específico, mientras que las fluctuaciones podrían surgir como resultado de la tolerancia y la regeneración dentro del hígado. Estas pruebas son importantes para el diagnóstico de lesiones inducidas por radiación, así como para la evaluación de la severidad y el tratamiento correcto de las mismas.

Serum lipids, proteins and electrolyte profiles in rats following total body irradiation / Perfiles de lípidos, proteínas y electrolitos plasmáticos en ratas tras irradiación corporal total

OBJECTIVE: Serum lipid and electrolyte imbalances are common in critically ill patients undergoing radiation therapy. Although multiple disease states and medication may be responsible for the development of these disorders, the aim of this research is to sequentially document the effect of total body radiation on body function utilizing the sequential changes in the serum lipids, electrolytes and protein in rats. METHODS: Serum protein and lipids contents were assessed using kits while electrolytes were assessed with flame photometry in rats exposed to total body irradiations of 1.27 Gy/min in cumulative doses to the fourth irradiation at five-day intervals. RESULTS: Total cholesterol and triacylglycerols serum levels were significantly reduced by irradiation (p < 0.05). No significant differences between experimental and control groups for HDL-C serum levels were detected. Serum electrolyte concentration remained within the normal range after each total body irradiation. Sodium, bicarbonate and chloride were significantly (p < 0.05) higher than control while potassium and creatinine were significantly reduced after the first irradiation only. Sodium/potassium ratio was significantly (p < 0.05) elevated. Serum protein was significantly (p < 0.05) elevated with increasing radiation. CONCLUSION: There are subtle but significant changes in serum lipids, electrolytes and protein after total body irradiation of normal rats. These variations could be due to non-specific stress reactions; as such, they are important markers in radiation induced injury diagnosis.

OBJETIVO: Los desequilibrios de lípido y electrolito plasmáticos son comunes en los pacientes críticos sometidos a terapia radioactiva. Aunque los múltiples estados de la enfermedad y la medicación pueden ser responsables del surgimiento de estos trastornos, el objetivo de esta investigación es documentar de manera secuencial el efecto de la radiación corporal total sobre la función corporal, utilizando los cambios secuenciales en los lípidos, electrolitos y proteínas plasmáticos en las ratas. MÉTODOS: Los contenidos de lípidos y proteínas plasmáticos fueron evaluados utilizando kits, en tanto que los electrolitos fueron evaluados mediante fotometría de llama en ratas expuestas a irradiaciones corporales totales de rayos X de 1.27 Gy/min, en dosis cumulativas hasta la cuarta irradiación en intervalos de cinco días. RESULTADOS: El colesterol total y los niveles plasmáticos de triacilgliceroles fueron reducidos significativamente por la irradiación (p < 0.05). No se detectaron diferencias significativas entre; os grupos experimentales y de control en relación con los niveles plasmáticos de colesterol HDL. La concen-tración de electrolito plasmático se mantuvo dentro de los límites normales luego de cada irradiación corporal total de rayos X. La relación sodio/potasio fue significativamente elevada (p < 0.05). La proteína plasmática se elevaba significativamente (p < 0.05) al aumentar la radiación. CONCLUSIÓN: Tras la irradiación corporal total de las ratas normales, seproducen cambios sutiles pero significativos en los lípidos, electrolitos y proteínas del plasma. Estas variaciones podrían ser debidas a reacciones de estrés no específicas, y como tal, son marcadores importantes en el diagnóstico de las lesiones inducidas por la radiación.