Telomere length and telomerase activity of leukocytes as biomarkers of selective serotonin reuptake inhibitor responses in patients with major depressive disorder.

We analyze the leukocyte telomere length (LTL) and telomerase activity in patients with major depressive disorder (MDD) before and after treatment with selective serotonin reuptake inhibitors (SSRIs). Before treatment, there was a reduction in the LTLs and expression levels of the human telomerase reverse transcriptase (hTERT) in the patients with MDD compared with controls. However, after 24 weeks of treatment with SSRIs, there was a significant increase in the LTLs and the expression levels of hTERT, with values approaching those observed in the controls. We conclude that SSRI antidepressant therapy can directly influence the increased expression levels of hTERT in patients.

In vitro assessment of cytotoxic, genotoxic and mutagenic effects of antimalarial drugs artemisinin and artemether in human lymphocytes.

Artemisinin is a substance extracted from the Chinese plant Artemisia annua L. widely used in natural medicine for the treatment of various diseases. Artemether is a substance synthesized from artemisinin, and both drugs are commonly administered in the treatment of malaria. Although considered effective antimalarial drugs, very little is known about the genotoxic, cytotoxic and mutagenic effects of these drugs. Therefore, in the present study, we evaluated the genotoxic, mutagenic and cytotoxic effects of artemisinin (12.5, 25 and 50 µg/mL) and artemether (7.46; 14.92 and 29.84 µg/mL) in cultured human lymphocytes using the comet assay, the micronucleus test and the cytotoxicity assay for detection of necrosis and apoptosis by acridine orange/ethidium bromide staining. Our results showed a significant increase (p < 0.05) in the rate of DNA damage measured by comet assay and in the micronucleus frequency after treatment with both drugs. It was also observed that only artemisinin induced a statistically significant increase (p < 0.05) in the number of lymphocytes with death by necrosis 48 h after treatment. The results demonstrated that these two drugs induce mutagenic, genotoxic and cytotoxic effects in cultured human lymphocytes. Our data indicate the need for caution in the use of such drugs, since genotoxic/mutagenic effects may increase the risk of carcinogenesis.

Genetic diversity of Hepatozoon spp. in Hydrochoerus hydrochaeris and Pecari tajacu from eastern Amazon.

This study aimed to identify and characterize genetically species of the genus Hepatozoon detected in Hydrochoerus hydrochaeris (capybaras) and Pecari tajacu (collared peccaries) from two localities from the Eastern Amazon. Blood samples from 196 free-living H. hydrochaeris from Marajó Island and 109 P. tajacu kept in captivity in Belém, Pará, were collected and analyzed for the presence of Hepatozoon spp. Partial sequences of the 18S rRNA gene were obtained and analyzed in comparison to others available in the NCBI database. Our results demonstrated a high prevalence of Hepatozoon canis in both mammals and the existence of four haplotypes of Hepatozoon spp., three of Hepatozoon canis and one of Hepatozoon cuestensis, found only in H. hydrochaeris. In addition, these data increase the genetic diversity of H. canis from the Eastern Amazon, as well as reporting, for the first time, the infection of mammals by H. cuestensis and P. tajacu by H. canis.

Chromosome X aneuploidy in Brazilian schizophrenic patients.

The identification of cytogenetic abnormalities in schizophrenic patients may provide clues to the genes involved in this disease. For this reason, a chromosomal analysis of samples from 62 schizophrenics and 70 controls was performed with trypsin-Giemsa banding and fluorescence in situ hybridization of the X chromosome. A clonal pericentric inversion on chromosome 9 was detected in one male patient, and we also discovered mosaicism associated with X chromosome aneuploidy in female patients, primarily detected in schizophrenic and normal female controls over 40 years old. When compared with age-matched female controls, the frequency of X chromosome loss was not significantly different between schizophrenics and controls, except for the 40- to 49-year-old age group. Our findings suggest that the X chromosome loss seen in schizophrenic patients is inherent to the normal cellular aging process. However, our data also suggest that X chromosome gain may be correlated with schizophrenia in this Brazilian population.

Reconstrução craniofacial com retalhos microcirúrgicos: análise crítica / Craniofacial reconstruction with free flaps: a critical analysis

Introdução: Os defeitos craniofaciais após ressecção tumoral representam uma situação extrema em cirurgia reparadora devido à complexidade das estruturas envolvidas, pela configuração tridimensional do defeito e pelo grande impacto funcional e estético que implicam. Portanto, a utilização de retalhos livres tornou-se uma grande opção para as reconstruções envolvendo a região craniofacial. Métodos: Análise retrospectiva de 23 prontuários médicos de pacientes submetidos à ressecção de tumores da região craniofacial e que foram submetidos à reconstrução com retalhos microcirúrgicos no período de janeiro de 2005 a dezembro de 2007. Foram avaliados: variáveis demográficas; tipo histológico do tumor; retalho utilizado; índice de sucesso e complicações. Resultados: O tipo histológico mais comum foi o carcinoma espinocelular com 35%, seguido do carcinoma basocelular com 26%. O retalho microcirúrgico mais utilizado foi o reto abdominal com 40%, seguido do retalho ântero-lateral da coxa com 24%. As complicações imediatas e tardias foram de 26%, com índice de sucesso de 95,6%. Conclusão: Tendo em vista a magnitude do defeito residual após a ressecção tumoral, a reconstrução com retalhos microcirúrgicos apresenta-se como opção segura, em tempo único e com baixo índice de complicações, oferecendo ao paciente um rápido restabelecimento e retorno ao convívio familiar.

Introduction: Craniofacial defects after tumor resection represent an extreme situation in reconstructive surgery, because of the complex structure, the three dimensional configuration of the wound and a huge functional and aesthetic impact. Therefore, the use of free flaps became a useful option for the reconstruction of craniofacial defects. Methods: Retrospective review of 23 medical charts of patients underwent tumor resection in craniofacial area and reconstructed with free flaps between January, 2005 and December, 2007. Results: Squamous cell carcinoma was the most frequent histological type with 35%, followed by basal cell carcinoma with 26%. The rectus abdominis free flap was used in 40% and anterolateral thigh free flap was used in 24%. Immediate and late complications were seen in 26%. Success rate was 95.6%. Conclusion: Because the magnitude of residual defect after tumor ablation, the use of free flaps become mandatory and permit a better functional and aesthetic results with lower rates of complications.

Acesso subcranial minimamente invasivo: alternativa cirúrgica para ressecção de tumores da base do crânio anterior / Minimally invasive subcranial approach: a surgical alternative for the ressection of anterior skull base tumors

Objetivo: descrever e anlisar nossa experiência em ressecção de tumores craniofaciais através de um acesso subcranial modificado, minimamente invasivo, desenvolvido por nós. Pacientes e método: estudo prospectivo com 26 pacientesapresentando tumores pequenos na base do crânio anterior, trtados nas Seções de Cirurgia de Cabeça e Pescoço e de Neurocirurgia do INCA-MS-RJ, no período de março de 2000 a setembro de 2006, operados pela mesma equipe cirúrgica, utilizando a técnica inovadora subcranial minimamente invasiva. Comparamos nossos resultados com resultados já publicados em literatura dos nossos pacientes submetidos à cirurgia craniofacial clássica, assim como com dados de literatura mundia. Resultados: dos 26 pacientes, 14 eram do gênero masculino. A idade média foi de 45,7 anos. O acesso subcranial isolado sem incisões faciais foi utilizado em seis casos. O tempo cirúrgico médio foi de 8,38 horas. A média de internação na unidade de terapia intensiva foi de 1,2 dias e de internação hospitalar de 7,8 dias. Não observamos complicações neurológicas imediatas. O índice de complicações foi de 28,5% com mortalidade operatória nula. A sobrevida global (para tumores malignos) foi de 61,9%. Conclusão: trata-se de um acesso inovador, onde podemos observar alguns benefícios notáveis, como a redução de complicações neurológicas gerais, tendência a reduzir o tempo cirúrgico, baixa taxa de hemotransfusão, menor tempo de internação em terapia intensiva e hospitalar e praticabilidade para tumores faciais acometendo o platô cribiforme ou discreta invasão da fossa craniana anterior.

Objective: to describe and to analyze our experience with the resection of craniofacial tumors throughe a modified minimally invasive subcranial access, developed by us. Patients and methods: prospective study with 26 patients presenting small tumors in the anterior skull base, treated in the Section of Head and Neck Surgery and Neurosurgery (INCA-MS-RJ), in the period from March, 2000 to September, 2006. The same surgical team was responsible for all surgeries using the innovative minimally invasive surgical technique. We compare the results of this technique with the results already published in the literature of our own patients treated by the classic cranialfacial technique, as well as, with data of worldwide literature. Results: of the 26 patients, 14 were men. The average age was of 45.7. The isolated subcranial access without face incisions was employed in 6 cases. The average surgical time was of 8.38h. The average stay in the intensive care unit was 1.2 days and the hospitalization time was 7.8 days. We did not observe immediate neurological complications. The complications incidence was 28.5%, without surgical death. The overall survival rate was 61.9% for malignant tumors. Conclusion: this is an innovative surgical approach in which we could observe some notables benefits, such as the reduction of neurological and general complications, trend to reduce to reduce the surgical time, low tax of hemotransfusion, minor time of stay under intensive care and in the hospital, and practicability for facial tumors resection, involving the cribriform plate or small invasion of the anterior skull base.

Cytogenetic characteristics of patients with signs and symptoms of myelodysplastic syndromes in the State of Pará, Brazil.

The myelodysplastic syndromes (MDS) are clonal hematopoietic diseases characterized by medullary dysplasia, cytopenias, and frequent evolution to acute myeloid leukemia. In 1982, the French-American-British (FAB) group proposed a classification for the MDS, based on morphological characteristics of peripheral blood and of the bone marrow. Later, cytogenetics proved to be a useful tool for the refinement of prognosis, through the use of the International Prognosis Score System (IPSS), as well as through evidence of clonality. Recently, the World Health Organization (WHO) proposed a new classification for the MDS, based on significant modifications of the FAB proposal, with the inclusion of chromosome analysis. A cytogenetic analysis was made of 17 patients with symptoms of MDS in the State of Para, based on WHO recommendations, and application of the IPSS. Good metaphases were obtained for 13 patients; 12 had a normal karyotype and only one had a clonal abnormality, del(3)(p25). The genes related to neoplastic processes that have been mapped to 3p are: XPC in 3p25.1 and FANCD2 and VHL in 3p25-26. Four patients had classic symptoms of MDS; in the rest the possibility of MDS was excluded or several months of observation before diagnosis were recommended. Among those with MDS, it was not possible to apply IPSS and WHO recommendations, because fundamental data were lacking, specifically the medullary blast and ring sideroblast counts. We advocate the implementation of routine cytogenetic analyses for the study of MDS, especially in patients with moderate hematopoietic dysplasia.

Síndromes mielodisplásicas: revisão dos esquemas de classificação / Myelodysplastic syndromes: classification schemes review

Introdução: As síndromes mielodisplásicas (SMD) são doenças clonais das células-tronco hematopoiéticas caracterizadas por hematopoiese ineficiente e freqüente evolução para leucemia mielóide aguda. Em 1982, o Grupo Franco-Americano-Britânico (FAB) propôs classificação para as SMD, baseada em características morfológicas no sangue periférico e medula óssea. Recentemente a organização Mundial de Saúde (OMS) publicou uma classificação revisada das SMD, baseada em modificações significantes da proposta FAB. Objetivo: Enfocar as principais diferenças entre os dois esquemas referidos de classificação. Método: Material pesquisado no banco de dados da Biblioteca Nacional de Medicina e do Centro Nacional para Informação em Biotecnologia dos Estados Unidos, com os termos: "síndromes "mielodisplásicas", "câncer", "classificação", "prognóstico", "revisão", "FAB", "OMS". Foram selecionados apenas artigos publicados em in-ês entre 1976 e 2004. Considerações Finais: A classificação da OMS das SMD foi construí da a partir do bem sucedido esquema FAB, da qual clínicos e patologistas estão familiarizados, e suas mudanças incluem dados citogenéticos e o refinamento dos critérios de diagnóstico. Contudo, como todos os esquemas de classificação, proposta da OMS deve ser considerada um trabalho em progressão e, à medida que forem acumuladas evidências sobre o significado de lesões genéticas específicas e características clínicas, revisões serão necessárias

Investigation of single strand conformational alterations of the TP53 gene in epithelial hyperplasias of the breast

Generally, benign breast lesions behave as innocuous and limited proliferations, but sometimes they can represent pre-cancerous diseases. The practical importance of epithelial hyperplasias studies is related to their potential for malignant transformation. The TP53 tumor supressor gene suffers the greatest number of mutations in human cancer Using single strand conformational polymorphism, we did a mutation screening in exons 5 to 8 of the TP53 gene in the tumoral tissues of five patients with epithelial hyperplasias of the breast. The obtained results do not show any polymorphism that indicates mutation. The lack of mutation indicates that this gene is not involved in the initial process of malignization, strengthening the hypothesis that mutations on TP53 gene are a late event in the breast carcinogenesis.