RESUMO
PURPOSE: The ability to measure oxidative DNA damage in a tissue allows establishment of the relationship between DNA damage and mutations in normal and neoplastic cells. It is well known that TP53 is a key inhibitor of tumor development and preserves the genome integrity in each cell. The aim of the present study was to investigate the relationship between DNA damage and TP53 mutation in colorectal adenoma and adenocarcinoma, and the value of DNA damage as potential marker of TP53 mutation in non-tumor tissues adjacent to colon malignant lesions. METHODS: Tissue samples were obtained by colonoscopy from patients with adenoma and/or adenocarcinoma and from healthy volunteers. Diagnosis was defined by histopathology. Immunohistochemistry with computer-assisted image analysis was performed to quantify TP53 mutation. Oxidative DNA damage was determined by comet assay. Statistical analyses were performed with 5 % of significance level. RESULTS: The TP53 level was higher in non-tumor tissues from tumor patients than in normal tissues from healthy volunteers (p = 0.01). Likewise, higher TP53 levels were observed in tumor tissues compared with the non-tumor tissues (p = 0.00). Oxidative DNA damage levels were higher in tumor tissues than in non-tumor tissues (p = 0.00). The amount of TP53 (p = 0.00) and oxidative DNA damage (p = 0.00) in normal and tumor tissue was related. The relationship between oxidative DNA damage and TP53 mutation was demonstrated in all samples (p = 0.00). CONCLUSION: Oxidative DNA damage is an intervening variable for TP53 mutation in colorectal adenoma-carcinoma. Our data suggests that oxidative DNA damage is a potential marker of TP53 mutation in colorectal carcinogenesis.
Assuntos
Neoplasias Colorretais/genética , Dano ao DNA , Proteína Supressora de Tumor p53/genética , Neoplasias Colorretais/patologia , Feminino , Genes p53 , Humanos , Imuno-Histoquímica , Masculino , MutaçãoRESUMO
INTRODUCTION: Knowledge of prognostic factors in end-stage renal disease patients has improved dialysis management and methods for reducing morbidity and mortality, underlining the importance of identification, prevention and control of these factors. OBJECTIVE: Identify factors affecting prognosis (survival or death) in hemodialysis patients at the Medical-Surgical Research Center in Havana over a ten-year period. METHODS: Descriptive, prospective study of 81 end-stage renal disease patients who received hemodialysis at the Medical-Surgical Research Center from 1995 to 2004. Prognostic factors were identified at initiation of and during dialysis treatment, using chi square, t test, McNemar test, Kaplan Meier analysis, log-rank test and Cox regression model, with significance threshold set at p <0.05. RESULTS: Hypertension and diabetes were the leading causes of end-stage renal disease. Six patients were referred late. Mean survival was 4.4 years; with survival of 86.6%, 54.7% and 26.6% at one, three and five years respectively. Factors predictive of decreased survival that were most frequent at initiation of hemodialysis were hypertension and chronic anemia (both present in 95.9% of cases); malnutrition, hypoalbuminemia, cardiovascular disease and chronic liver disease increased during treatment while hypertension decreased. In multivariate analysis, prognostic factors that significantly predicted decreased survival were hypertension, inadequate vascular access and diabetes. Patients aged ≥ 60 years and those with malnutrition, hypoalbuminemia, anemia, cardiovascular disease or liver disease had lower survival figures at the end of the study period. Leading causes of death were infections (45.2%) and cardiovascular disease (41.9%); the latter was present in 93.5% of deaths, independent of underlying cause of death. CONCLUSIONS: Survival of hemodialysis patients diminished at five years. Some negative predictive factors are present at initiation of hemodialysis, such as diabetes, hypertension and chronic anemia; others increased later, including malnutrition, hypoalbuminemia, cardiovascular disease and liver disease.
Assuntos
Falência Renal Crônica/diagnóstico , Diálise Renal/mortalidade , Adulto , Anemia/complicações , Cuba/epidemiologia , Feminino , Humanos , Hipertensão/complicações , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Masculino , Prognóstico , Estudos Prospectivos , Análise de SobrevidaRESUMO
PURPOSE: Oxidative DNA damage is one of the mechanisms associated to initial colorectal carcinogenesis, but how it interacts with ß-catenin, an adherence protein related to cancer evolution, is not clear. This study investigates the relationship between oxidative DNA damage and ß-catenin expression in normal mucosa and colon tumor tissue (adenoma and adenocarcinoma) in colorectal adenocarcinoma evolution. METHOD: One hundred and 13 samples were studied. Hematoxylin-eosin determined histological grade. ß-Catenin expression was analyzed by immunohistochemistry. The oxidative DNA damage was evaluated using comet assay technique. The coefficient for rejection of the nullity hypothesis was taken to 5 %. Kruskal-Wallis, Spearman test, and partial correlation were used to analyze the data. RESULTS: There was oxidative DNA damage increase in colorectal cancer evolution (p < 0.01). Histological grade was correlated with oxidative DNA damage (p < 0.01). There were differences in ß-catenin expression among normal, adenoma, and adenocarcinoma tissue with progressive increase of ß-catenin expression (p < 0.00). Histological grade was correlated to ß-catenin expression (p < 0.00). There was a relationship (p < 0.00) between ß-catenin and histological grade while controlling for the effect of oxidative DNA damage. CONCLUSION: The findings of this study make it possible to establish a relationship between oxidative DNA damage and ß-catenin expression in normal mucosa and colorectal tumor tissue. Additionally, they show a causal relationship between variations of ß-catenin in different tissues analyzed while controlling for the effect of oxidative DNA damage.
Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Dano ao DNA , Progressão da Doença , Estresse Oxidativo , beta Catenina/metabolismo , Colo/metabolismo , Colo/patologia , Humanos , Pessoa de Meia-IdadeRESUMO
Se presentó el caso de un paciente con transplante renal, de 64 años, trabajador de una granja avícola, que sufrió una meningoencefalitis a los 6 meses de recibir tratamiento inmunosupresor. El diagnóstico rápido se realizó a partir de una muestra de líquido cefalorraquídeo mediante el empleo de partículas de látex para la detección de antígeno de Cryptococcus spp. Después se confirmó con el cultivo de la muestra clínica empleando agar-Sabouraud-cloranfenicol; la identificación bioquímica se realizó con el sistema API 20C AUX. Inmediatamente se inició el tratamiento con anfotericina B, con posterior cambio a fluconazol hasta negativizar los exámenes microbiológicos. Pasados 5 meses presentó una recaída, y se reinició el tratamiento específico. Se le dio seguimiento por consulta y presentó una evolución favorable hasta 2 años después del trasplante de órgano(AU)
This article presented the case of a 64 years-old renal transplant recipient, who was a poultry farm worker and had suffered meningoencephalitis six months after receiving immunosuppressive therapy. Rapid diagnosis was based on a cerebrospinal fluid sample analyzed with latex particles for Cryptococcus spp antigen detection. Culture of the clinical sample in agar-Sabouraund-chloramphenicol medium confirmed the initial diagnosis whereas biochemical identification was made with the API 20C AUX system. Amphotericin B treatment was immediately applied to the patient and later fluconazole until microbiological tests yielded negative results. After 5 months, the patient relapsed and restarted the specific treatment. He was followed up on outpatient service and two year after the organ transplantation, his recovery was favourable(AU)
Assuntos
Humanos , Masculino , Transplante de Rim , Imunossupressores/efeitos adversos , Meningoencefalite/diagnóstico , Meningoencefalite/terapiaRESUMO
Se presentó el caso de un paciente con transplante renal, de 64 años, trabajador de una granja avícola, que sufrió una meningoencefalitis a los 6 meses de recibir tratamiento inmunosupresor. El diagnóstico rápido se realizó a partir de una muestra de líquido cefalorraquídeo mediante el empleo de partículas de látex para la detección de antígeno de Cryptococcus spp. Después se confirmó con el cultivo de la muestra clínica empleando agar-Sabouraud-cloranfenicol; la identificación bioquímica se realizó con el sistema API 20C AUX. Inmediatamente se inició el tratamiento con anfotericina B, con posterior cambio a fluconazol hasta negativizar los exámenes microbiológicos. Pasados 5 meses presentó una recaída, y se reinició el tratamiento específico. Se le dio seguimiento por consulta y presentó una evolución favorable hasta 2 años después del trasplante de órgano.
This article presented the case of a 64 years-old renal transplant recipient, who was a poultry farm worker and had suffered meningoencephalitis six months after receiving immunosuppressive therapy. Rapid diagnosis was based on a cerebrospinal fluid sample analyzed with latex particles for Cryptococcus spp antigen detection. Culture of the clinical sample in agar-Sabouraund-chloramphenicol medium confirmed the initial diagnosis whereas biochemical identification was made with the API 20C AUX system. Amphotericin B treatment was immediately applied to the patient and later fluconazole until microbiological tests yielded negative results. After 5 months, the patient relapsed and restarted the specific treatment. He was followed up on outpatient service and two year after the organ transplantation, his recovery was favourable.
Assuntos
Humanos , Masculino , Imunossupressores/efeitos adversos , Transplante de Rim , Meningoencefalite/diagnóstico , Meningoencefalite/terapiaRESUMO
This article presented the case of a 64 years-old renal transplant recipient, who was a poultry farm worker and had suffered meningoencephalitis six months after receiving immunosuppressive therapy. Rapid diagnosis was based on a cerebrospinal fluid sample analyzed with latex particles for Cryptococcus spp antigen detection. Culture of the clinical sample in agar-Sabouraund-chloramphenicol medium confirmed the initial diagnosis whereas biochemical identification was made with the API 20C AUX system. Amphotericin B treatment was immediately applied to the patient and later fluconazole until microbiological tests yielded negative results. After 5 months, the patient relapsed and restarted the specific treatment. He was followed up on outpatient service and two year after the organ transplantation, his recovery was favourable.