Impact of cerebrovascular risk factors over the evolution of dementia due to Alzheimer's disease in a sample of patients with low schooling from Sao Paulo, Brazil

The objective of this paper is to evaluate the impact of cerebrovascular risk factors over the rate of progression of Alzheimer's disease in a sample of patients with low schooling. Lower schooling, but not cerebrovascular risk, had a significant effect for a faster rate of progression of Alzheimer's disease, assessed by way of MMSE and CDR scores.Fed Univ Sao Paulo UNIFESP, Escola Paulista Med, Sao Paulo, BrazilFed Univ Sao Paulo UNIFESP, Escola Paulista Med, Sao Paulo, BrazilWeb of Scienc

Sleep in the neuropsychiatric evaluation of patients with dementia due to Alzheimer's disease

The objective of this paper is to evaluate the amount of sleep of patients with Alzheimer's disease, as well as which factors might influence their sleep patterns. After the assessment of 131 patients with dementia due to Alzheimer's disease, we concluded that low schooling impacts the evolution of these patients as much as their sleep patterns, which are likewise affected by neuropsychiatric symptoms. Also, satisfactory sleep seems to be related to its length for such patients.Fed Univ Sao Paulo UNIFESP, Escola Paulista Med, Sao Paulo, BrazilFed Univ Sao Paulo UNIFESP, Escola Paulista Med, Sao Paulo, BrazilWeb of Scienc

Effects of intellectual habits, leisure and physical activity over the age of onset and evolution of dementia due to Alzheimer's disease

The objective of this paper is to investigate whether intellectual, physical or leisure activities have an impact over age of onset or progression of Alzheimer's disease. We concluded that subjects who were concurrently engaged in various intellectual, physical and leisure activities earlier during their lives were less likely to develop dementia due to Alzheimer's disease before turning 80 years-old.Fed Univ Sao Paulo UNIFESP, Escola Paulista Med, Sao Paulo, BrazilFed Univ Sao Paulo UNIFESP, Escola Paulista Med, Sao Paulo, BrazilWeb of Scienc

Epidemiology of dementia in Sao Paulo, Brazil: risk factors and age of onset of dementia due to Alzheimer's disease

The objective of this paper is to investigate the impact of previously reported sporadic risk factors over the age of onset of Alzheimer's disease in a Brazilian sample. The survey included 129 patients with late-onset Alzheimer's disease, assessed for gender, schooling, cerebrovascular risk, history of brain trauma with loss of consciousness, systemic infections, and family history of Alzheimer's disease, neurological disorders other than Alzheimer's disease, brain diseases in general, or cardiovascular diseases. We concluded that environmental, educational and demographic factors did not seem to be significantly related to the age of onset of Alzheimer's disease on this sample.Fed Univ Sao Paulo UNIFESP, Escola Paulista Med, Sao Paulo, BrazilFed Univ Sao Paulo UNIFESP, Escola Paulista Med, Sao Paulo, BrazilWeb of Scienc

Cytogenetic effect of 5-azacytidine in patients with hematological malignancies

BACKGROUND: Recently, the importance of cytogenetics has grown in the diagnosis, prognosis and treatment of leukemias and myelodysplastic syndromes. 5-azacytidine is a drug that has well-known cytogenetical effects and is approved in the treatment of myelodysplastic syndromes. To date, no studies have been performed to evaluate the impact of 5-azacytidine on the chromosomes of patients with hematological neoplasias. This study aimed to investigate the effects of 5-azacytidine on chromosomes of patients with different hematological malignancies using G-band analyses to identify possible cytogenetical alterations. METHODS: The peripheral blood of 18 patients with hematological malignancies and 18 controls was collected in heparinized tubes. 5-azacytidine was added, at a final concentration of 10-5M, to cultures 7 hours prior to harvest. RESULTS: Uncoiled centromeric/pericentromeric heterochromatin of chromosomes-1, 9 and 16 occurred more frequently in the patients than in controls. This higher frequency of uncoiled heterochromatin was statistically significant (p-value = 0.004) for chromosome-9. Conversely, we observed that the fragile site at 19q13 was more frequent in controls (p-value = 0.0468). CONCLUSIONS: The results of this study suggest that satellite sequences, located in the heterochromatin of chromosome-9, are hypomethylated in hematological malignancies. This hypomethylation may contribute to the disease, activating transposable elements and/or promoting genomic instability, enabling the loss of heterozygosity of important tumor suppressor genes. An investigation of the 19q13 region may help to understand whether or not the predominant occurrence of the fragile site at 19q13 in controls is due to hypermethylation of this region.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Faculdade de Medicina de Marília Hemocentro Genetics LaboratoryUniversidade Federal de São Paulo (UNIFESP) Department de MorphologyFaculdade de Medicina de Marília Hematology DepartmentUniversidade do Sagrado CoraçãoUNIFESP, Department de MorphologySciEL

cagA positive Helicobacter pylori in Brazilian children related to chronic gastritis

Helicobacter pylori is a spiral-shaped Gram-negative bacterium. It colonizes the gastric mucosa of humans and persists for decades if not treated. Helicobacter pylori infection affects more than half of the world's population and invariably results in chronic gastritis. The cagA gene is present in about 60 to 70% of H. pylori strains; it encodes a high-molecular-weight protein (120 to 140 kDa) and several investigators have noted a correlation between strains that possess cagA and the severity of gastric mucosal inflammation. We examined the relation between cagA status in H. pylori strains and chronic gastritis with inflammatory processes in children from Marília, São Paulo, Brazil. One-hundred-twenty-one children were analyzed histopathologically and by polymerase chain reaction (PCR) to detect H. pylori and cagA. We then looked for an association between cagA presence and inflammatory infiltration. Using histology and PCR, we found 47% H. pylori positive infection; 29 children were diagnosed with chronic gastritis, while 28 showed normal mucosa by histopathological analysis. CagA presence was genotyped in both groups, and an inflammatory infiltrate was studied in all infected children with chronic gastritis. We found cagA strains in 20 of 29 (69%) children with chronic gastritis and 18 of 28 (64%) with normal mucosa, demonstrating a strong relationship between the strains and the inflammatory process. We found a positive association between an inflammatory process associated with H. pylori of cagA+ strains and chronic gastritis development.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)School of Medicine of Marília Department of Genetic and Molecular Biology HemocentroUNIFESP-EPM Department of GeneticFAMEMA Department of PathologyUNIFESP, EPM, Department of GeneticSciEL

Cytotoxicity and genotoxicity of low doses of mercury chloride and methylmercury chloride on human lymphocytes in vitro

Mercury is a xenobiotic metal that is a highly deleterious environmental pollutant. The biotransformation of mercury chloride (HgCl2) into methylmercury chloride (CH3HgCl) in aquatic environments is well-known and humans are exposed by consumption of contaminated fish, shellfish and algae. The objective of the present study was to determine the changes induced in vitro by two mercury compounds (HgCl2 and CH3HgCl) in cultured human lymphocytes. Short-term human leukocyte cultures from 10 healthy donors (5 females and 5 males) were set-up by adding drops of whole blood in complete medium. Cultures were separately and simultaneously treated with low doses (0.1 to 1000 µg/l) of HgCl2 and CH3HgCl and incubated at 37ºC for 48 h. Genotoxicity was assessed by chromosome aberrations and polyploid cells. Mitotic index was used as a measure of cytotoxicity. A significant increase (P < 0.05) in the relative frequency of chromosome aberrations was observed for all concentrations of CH3HgCl when compared to control, whether alone or in an evident sinergistic combination with HgCl2. The frequency of polyploid cells was also significantly increased (P < 0.05) when compared to control after exposure to all concentrations of CH3HgCl alone or in combination with HgCl2. CH3HgCl significantly decreased (P < 0.05) the mitotic index at 100 and 1000 µg/l alone, and at 1, 10, 100, and 1000 µg/l when combined with HgCl2, showing a synergistic cytotoxic effect. Our data showed that low concentrations of CH3HgCl might be cytotoxic/genotoxic. Such effects may indicate early cellular changes with possible biological consequences and should be considered in the preliminary evaluation of the risks of populations exposed in vivo to low doses of mercury.Faculdade de Itaituba Departamento de Pós-GraduaçãoUniversidade Federal do Pará Centro de Ciências Biológicas Departamento de BiologiaUniversidade Federal do Pará Centro de Ciências Biológicas Departamento de PatologiaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de GenéticaFundação Universidade Federal de Rondônia Departamento de Medicina Laboratório de Biogeoquímica AmbientalUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MorfologiaUNIFESP, EPM, Depto. de MorfologiaSciEL

Cytogenetic characterization and evaluation of c-MYC gene amplification in PG100, a new Brazilian gastric cancer cell line

Gastric cancer is the fourth most frequent type of cancer and the second cause of cancer mortality worldwide. The genetic alterations described so far for gastric carcinomas include amplifications and mutations of the c-ERBB2, KRAS, MET, TP53, and c-MYC genes. Chromosomal instability described for gastric cancer includes gains and losses of whole chromosomes or parts of them and these events might lead to oncogene overexpression, showing the need for a better understanding of the cytogenetic aspects of this neoplasia. Very few gastric carcinoma cell lines have been isolated. The establishment and characterization of the biological properties of gastric cancer cell lines is a powerful tool to gather information about the evolution of this malignancy, and also to test new therapeutic approaches. The present study characterized cytogenetically PG-100, the first commercially available gastric cancer cell line derived from a Brazilian patient who had a gastric adenocarcinoma, using GTG banding and fluorescent in situ hybridization to determine MYC amplification. Twenty metaphases were karyotyped; 19 (95%) of them presented chromosome 8 trisomy, where the MYC gene is located, and 17 (85%) presented a deletion in the 17p region, where the TP53 is located. These are common findings for gastric carcinomas, validating PG100 as an experimental model for this neoplasia. Eighty-six percent of 200 cells analyzed by fluorescent in situ hybridization presented MYC overexpression. Less frequent findings, such as 5p deletions and trisomy 16, open new perspectives for the study of this tumor.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal do Pará Instituto de Ciências Biológicas Laboratório de Citogenética HumanaUniversidade Federal de São Paulo (UNIFESP) Disciplina de GenéticaUNIFESP, Disciplina de GenéticaCNPq: 20/2007CNPq: 550885/2007-2SciEL

Gene polymorphism of interleukin 1 and 8 in chronic gastritis patients infected with Helicobacter pylori

Background: Epidemiological investigations have indicated that Helicobacter pylori induces inflammation in the gastric mucosa regulated by several interleukins. The genes IL1B and IL8 are suggested as key factors in determining the risk of gastritis. The aim of this paper was to evaluate the association of gene polymorphism of interleukin-1 and interleukin-8 with chronic gastrits in H. pylori infected patients. A total of 60 patients underwent endoscopic procedure. Biopsy samples were collected for urease test, histopathological and molecular exams. The DNA of theses samples was extracted for detection of H. pylori and analysis of the genes mentioned above. Patients with gastritis had a higher frequency of H. pylori-positive samples. Result: H. pylori was detected in 30/60 patients (50%) by PCR. As for polymorphism of interleukin 8 (-251) gene we observed a statistical difference when analyzed TA (p = 0.039) and TT (p = 0.047) genotypes. In the IL1B31 there was a statistical difference in TT (p = 0.01) genotype and in theIL1B-511 there wasn’t any statistical difference. Conclusion: Our results suggest a strong correlation between the presence of chronic gastritis and infection byH. pylori and that IL1B-31TT and IL8-251TT genotypes appear to act as protective factors againstH. pylori infection while IL8-251TA genotype may comprise a risk factor for infection with this bacterium.Marília Medical School FAMEMA Blood Center Department of GeneticsSacred Heart UniversityMarília Medical School Department of Digestive System SurgeryFederal University of São Paulo Department of MorphologyMarília Medical School Department of Radiotherapy and OncologyFAMEMA Hemocentro Laboratório de GenéticaUNIFESP, Department of MorphologySciEL

Methylation status of ANAPC1, CDKN2A and TP53 promoter genes in individuals with gastric cancer

Gastric cancer is the forth most frequent malignancy and the second most common cause of cancer death worldwide. DNA methylation is the most studied epigenetic alteration, occurring through a methyl radical addition to the cytosine base adjacent to guanine. Many tumor genes are inactivated by DNA methylation in gastric cancer. We evaluated the DNA methylation status of ANAPC1, CDKN2A and TP53 by methylation-specific PCR in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosa in individuals from Northern Brazil. All gastric cancer samples were advanced stage adenocarcinomas. Gastric samples were surgically obtained at the João de Barros Barreto University Hospital, State of Pará, and were stored at -80°C before DNA extraction. Patients had never been submitted to chemotherapy or radiotherapy, nor did they have any other diagnosed cancer. None of the gastric cancer samples presented methylated DNA sequences for ANAPC1 and TP53. CDKN2A methylation was not detected in any normal gastric mucosa; however, the CDKN2A promoter was methylated in 30.4% of gastric cancer samples, with 35% methylation in diffuse-type and 26.9% in intestinal-type cancers. CDKN2A methylation was associated with the carcinogenesis process for ~30% diffuse-type and intestinal-type compared to non-neoplastic samples. Thus, ANAPC1 and TP53 methylation was probably not implicated in gastric carcinogenesis in our samples. CDKN2A can be implicated in the carcinogenesis process of only a subset of gastric neoplasias.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FINEP/CT-INFRAFAEPAUniversidade Federal do Piauí Colegiado de BiomedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MorfologiaUniversidade Federal do Pará Instituto de Ciências Biológicas Laboratório de Citogenética HumanaHospital João de Barros Barreto Serviço de CirurgiaInstituto de Investigaciones BiomedicasUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de GenéticaUNIFESP, EPM, Depto. de MorfologiaFINEP/CT-INFRA: 0927-03SciEL