Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with mitochondrial DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder is characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased mitochondrial biogenesis in unaffected mutation carriers is a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking have been implicated as disease triggers. To investigate this issue further, we first assessed the relationship between cigarette smoke and mtDNA copy number in blood cells from large cohorts of LHON families, finding that smoking was significantly associated with the lowest mtDNA content in affected individuals. To unwrap the mechanism of tobacco toxicity in LHON, we exposed fibroblasts from affected individuals, unaffected mutation carriers and controls to cigarette smoke condensate (CSC). CSC decreased mtDNA copy number in all cells; moreover, it caused significant reduction of ATP level only in mutated cells including carriers. This implies that the bioenergetic compensation in carriers is hampered by exposure to smoke derivatives. We also observed that in untreated cells the level of carbonylated proteins was highest in affected individuals, whereas the level of several detoxifying enzymes was highest in carriers. Thus, carriers are particularly successful in reactive oxygen species (ROS) scavenging capacity. After CSC exposure, the amount of detoxifying enzymes increased in all cells, but carbonylated proteins increased only in LHON mutant cells, mostly from affected individuals. All considered, it appears that exposure to smoke derivatives has a more deleterious effect in affected individuals, whereas carriers are the most efficient in mitigating ROS rather than recovering bioenergetics. Therefore, the identification of genetic modifiers that modulate LHON penetrance must take into account also the exposure to environmental triggers such as tobacco smoke.

Visceral leishmaniasis (VL) caused by is a lethal disease transmitted by sand flies. Although, considered a zoonosis with dogs held as the main reservoirs, humans are also sources of infection. Therefore, control policies currently focused on dog culling may need to consider that VL and human immunodeficiency virus (HIV)/VL patients may also be infectious, contributing to transmission. Reservoir competence of patients with VL without and with HIV infection and of persons asymptomatically infected with was assessed by xenodiagnosis with the vector . Parasites in sand fly's guts were identified by using optical microscopy and by conventional polymerase chain reaction (PCR). blood parasite burden was determined by quantitative PCR. Among the 61 participants, 27 (44%) infected sand flies as seen by microscopy or PCR. When infectiousness was assessed by microscopy, xenodiagnosis was positive in five (25%) patients not infected with HIV, whereas nine (45%) of those harboring HIV were positive. Among the 19 asymptomatic patients four (21%) infected sand flies only demonstrated by PCR. One (50%) asymptomatic patient with HIV had a positive xenodiagnosis by microscopy. 9/372 (2.4%) and 37/398 (9.2%) sand flies were infected when feeding in patients without and with HIV, respectively. Infectiousness was poorly correlated with quantitative PCR. The study shows that asymptomatic humans are capable of transmitting , that ill persons with HIV infection are more infectious to sand flies, and that humans are more important reservoirs than previously thought. This fact may be considered when designing control policies for zoonotic VL.

No abstract

A síndrome de poliendocrinopatia autoimune tipo 1 (APS-1), também conhecida como distrofia ectodérmica-candidíase-poliendocrinopatia autoimune (APECED), é um distúrbio autossômico recessivo raro causado por mutações no gene regulador autoimune (AIRE). Sendo assim, ela é imunologicamente caracterizada pelo ataque celular e/ou mediada por anticorpos que gera a destruição de órgãos-alvo. Além disso, é marcada pela tríade patognomônica: candidíase crônica, hipoparatireoidismo e doença de Addison, com várias outras manifestações endócrinas e não endócrinas. Logo, o diagnóstico é feito com base na presença de duas dessas três características clássicas e o tratamento visa controlar as inúmeras deficiências que os pacientes possam apresentar. Esta revisão literária teve como objetivo a compreensão do envolvimento do gene AIRE em relação aos aspectos imunológicos presentes e, consequentemente, manifestações clínicas dessa doença. Assim, evidenciou-se a necessidade de ampliar a discussão sobre essa patologia, com o intuito de melhorar a qualidade de vida dos pacientes, mediante diagnóstico e tratamento precoces e que estejam de acordo com as manifestações clínicas de cada paciente. Desse modo, a pesquisa de caráter qualitativo envolveu artigos científicos dos periódicos eletrônicos LILACS (Literatura Latino-Americana e do Caribe), SCIELO (Scientific Electronic Library Online) e NCBI (National Center for Biotechnology Information), entre os anos 2009 e 2016. Por conseguinte, nota-se a relevância dessa revisão, pois observou-se que, apesar de os autores convergirem sobre as opiniões acerca dessa síndrome, há, ainda, muitas questões obscuras no que diz respeito aos mecanismos da doença. Isso evidencia a necessidade de se promoverem mais discussões sobre esse tema. https://doi.galoa.com.br/doi/10.17648/jibi-2448-0002-1-2-4937

No abstract

O câncer de mama masculino é um quadro neoplásico raro, abrange 1% dos casos de câncer de mama no mundo todo, 1% dos tumores malignos em homens e apresenta incidência anual de 1 por 100.000. Reuniram-se informações acerca da atualidade de estudos relacionados ao caráter genético na patologia abordada, cujo objetivo foi analisar aspectos da predisposição e associação, utilizando 15 artigos originais indexados no período entre janeiro de 2011 a fevereiro de 2016, escritos em inglês e espanhol, com delineamento experimental ou observacional, utilizando os descritores câncer de mama masculino, tratamento do câncer, câncer de mama e fator genético do câncer de mama, assim como suas traduções em inglês male breast cancer, cancer treatment, breast cancer e genetic factors. Discutiu-se principalmente a influência genética na ocorrência do câncer de mama masculino, como alterações em genes supressores BRCA, relações com o ponto de checagem CHECK2, histórico familiar e ligações com a síndrome de Klinefelter, entre outros fatores. Aspectos ambientais também são sugeridos por parte da literatura na manifestação clínica da neoplasia, porém com menores ênfases conclusivas. Apesar da literatura sobre o tema ainda necessitar de crescimento e aprofundamento, observaram-se reafirmações científicas sobre a importância da influência genética, sobretudo do BRCA 2, além de confirmações quanto a multifatoriedade da neoplasia.

No abstract

No abstract