Fibrose Cística: Diagnóstico e Tratamento

Fibrose Cística, também chamada de mucoviscidose, é uma doença crônica, de origem genética, causada por um gene defeituoso herdado do pai e outro da mãe. Não é, portanto, uma doença contagiosa. O defeito genético faz com que todas as glândulas secretoras do corpo sejam afetadas. É por este motivo que o suor é salgado, o muco que reveste as vias aéreas é mais espesso e a bile também é mais viscosa.

Cystic fibrosis respiratory infection and treatment

Fibrose cística é uma doença multissistêmica e complexa, que exige tratamento contínuo. A doença pulmonar é o principal determinante da sua evolução. Alterações na composição da secreção das vias aéreas levam ao desenvolvimento de doença pulmonar progressiva com infecção respiratória crônica por germes peculiares à doença. Esquemas de antibioticoterapia para tratamento das exacerbações pulmonares, erradicação de bactérias ou de supressão da infecção crônica constituem parte importante do tratamento, com repercussão significativa na melhora dos sintomas, da função pulmonar e da qualidade de vida dos pacientes com fibrose cística.Cystic fibrosis is a complex multisystemic disease that requires lifelong treatment. Pulmonary disease is the major prognostic determinant. The altered airway surface liquid leads to the development of progressive pulmonary disease with chronic respiratory infection by specific germs. Antibiotic strategies for treatment of pulmonary disease exacerbations, bacterial eradication or chronic infection suppression play an important role in the treatment, contributing to the improvement of symptoms, lung function and the quality of life of Cystic Fibrosis patients

Characterization of two novel proteins involved in mitochondrial DNA anchoring in Trypanosoma brucei.

Trypanosoma brucei is a single celled eukaryotic parasite in the group of the Kinetoplastea. The parasite harbors a single mitochondrion with a singular mitochondrial genome that is known as the kinetoplast DNA (kDNA). The kDNA consists of a unique network of thousands of interlocked circular DNA molecules. To ensure proper inheritance of the kDNA to the daughter cells, the genome is physically linked to the basal body, the master organizer of the cell cycle in trypanosomes. The connection that spans, cytoplasm, mitochondrial membranes and the mitochondrial matrix is mediated by the Tripartite Attachment Complex (TAC). Using a combination of proteomics and RNAi we test the current model of hierarchical TAC assembly and identify TbmtHMG44 and TbKAP68 as novel candidates of a complex that connects the TAC to the kDNA. Depletion of TbmtHMG44 or TbKAP68 each leads to a strong kDNA loss but not missegregation phenotype as previously defined for TAC components. We demonstrate that the proteins rely on both the TAC and the kDNA for stable localization to the interface between these two structures. In vitro experiments suggest a direct interaction between TbmtHMG44 and TbKAP68 and that recombinant TbKAP68 is a DNA binding protein. We thus propose that TbmtHMG44 and TbKAP68 are part of a distinct complex connecting the kDNA to the TAC

Mecanismos endócrinos e moleculares envolvidos na formação do corpo lúteo e na luteólise: revisão de literatura

The corpus luteum (CL) is a transitory endocrinal structure formed by steroidogenic small luteal cells (SLC) and large luteal cells (LLC) that associated with fibroblast and a wide web of capillaries form a structure specialized in synthesis of progesterone (P4). In general, for the synthesis of P4 in the steroidogenic luteal cells, cholesterol joints specific receptors on the cellular membrane and is transported to the cytosol. Later, cholesterol goes to an internal mitochondrial membrane and by the action of the enzyme P450scc is transformed into pregnenolone. In the smooth endoplasmic reticulum pregnenolone is converted to P4 by the enzyme 3²-hydroxysteroid dehydrogenase (3²-HSD). The steroidogenic acute regulatory protein (StAR), the peripheral benzodiazepine receptor (PBR) and endozepine participate in the transport of cholesterol to the different mitochondrial compartments. Therefore, it is supposed that the capacity of synthesis of P4 in the CL is related to the cellular concentration of receptors that catch cholesterol, to the enzymes P450scc and 3²-HSD and to the cholesterol cellular transport proteins. In bovine, the LLC are responsible for more than 80% of P4 production in the CL. The lowest concentration of cholesterol transport proteins in the mitochondria seems to limit the synthesis of P4 in the SLC. P4 supports a proper uterine environment for the development of conceptuses, depending on the specie. In most species, the lack of fertilization or the conceptus incapacity to signalize its presence in the uterus establishes luteolysis. This physiological event is characterized by the functional and structural regression of the CL. For the establishment and maintenance of pregnancy it is necessary to block luteolysis through different mechanisms among species. In primates and equids it occurs by the secretion of specific gonadotropins and in ruminants by antiluteolytic factors. This review has the objective to characterize the endocrine and molecular mechanisms involved in the formation of the corpus luteum and luteolysis.O corpo lúteo (CL) é uma estrutura endócrina transitória formada por células luteais esteroidogênicas pequenas (SLC) e grandes (LLC), que associadas aos fibroblastos e a uma ampla rede de capilares constituem uma estrutura especializada na síntese de progesterona (P4). De maneira geral, para a síntese de P4 nas células luteais esteroidogênicas, o colesterol se liga a receptores específicos na membrana celular e é transportado ao citosol. Posteriormente, o colesterol dirige-se a membrana mitocondrial interna e por ação da enzima P450scc transforma-se em pregnenolona. No retículo endoplasmático liso a pregnenolona é convertida a P4 pela enzima 3²-hidroxiesteróide deidrogenase (3²-HSD). A proteína de regulação aguda da esteroidogênese (StAR), o receptor benzodiazepínico tipo periférico (PBR) e a endozepina participam no transporte do colesterol para os diferentes compartimentos mitocondriais. Assim, supõe-se que a capacidade de síntese de P4 no CL esteja relacionada à concentração celular de receptores que captam o colesterol, às enzimas P450scc e 3²-HSD, e às proteínas celulares transportadoras de colesterol. Na espécie bovina, as LLC são responsáveis por mais de 80% da produção deste hormônio no CL. A menor concentração de proteínas transportadoras de colesterol na mitocôndria parecem limitar a síntese de P4 nas SLC. A P4 favorece um meio ambiente uterino apropriado para o desenvolvimento do(s) concepto(s), dependendo da espécie. Na maioria das espécies, a ausência da fertilização ou a incapacidade do concepto em sinalizar sua existência no útero estabelecem a luteólise. Tal evento fisiológico caracteriza-se pela regressão funcional e estrutural do(s) corpo(s) lúteo(s). Para o estabelecimento e a manutenção da prenhez torna-se necessário o bloqueio da luteólise por mecanismos que diferem entre as espécies. Em primatas e equídeos esse reconhecimento ocorre pela secreção de gonadotrofinas específicas e em ruminantes pela presença de fatores anti-luteolíticos. Esta revisão tem como objetivo caracterizar os mecanisnos endócrinos e moleculares envolvidos na formação do corpo lúteo e na luteólise

High-risk twin pregnancy : case report of an adolescent patient with cystic fbrosis and systemic lupus erythematosus

Background: We present the frst case to our knowledge of a spontaneous twin pregnancy in a 16-year-old Caucasian patient with cystic fbrosis and systemic lupus erythematosus. Cystic fbrosis is one of the most common autosomal recessive genetic disorders and primarily afects the respiratory and digestive systems. Systemic lupus erythematosus is a chronic infammatory disease of unknown cause that afects nearly every organ. Patients with cystic fbrosis or systemic lupus erythematosus are progressively having longer life expectancy and better quality of life, which has led a greater number of female patients reporting the desire to become mothers. Case presentation: We present a case of a Caucasian 16-year-old pregnant with twins being treated for both cystic fbrosis and systemic lupus erythematosus. She has two CFTR mutations: p.F508del and 1812_1G>A. In the second trimester, she was admitted for possible preterm labor, which was successfully stopped. The patient’s nutritional status worsened, and she had a pulmonary exacerbation as well as a fare of systemic lupus erythematosus. At the 28th gestational week, she presented with a massive hemoptysis episode. The cesarean delivery had no complications, and there were no serious immediate postpartum complications. Discussion and conclusions: While adolescent pregnancies in and of themselves are considered high risk for both the young mothers and their children, they are further complicated when the mother has two chronic diseases and a twin pregnancy. We achieved positive results using a multidisciplinary approach; however, the risks involved were so high that major eforts are to be taken by our medical community to prevent unplanned pregnancies in all patients with cystic fbrosis, especially when a serious comorbidity like the one in this case is present

Correction: TAC102 Is a Novel Component of the Mitochondrial Genome Segregation Machinery in Trypanosomes.

[This corrects the article DOI: 10.1371/journal.ppat.1005586.]

Molecular model of the mitochondrial genome segregation machinery in Trypanosoma brucei

In almost all eukaryotes, mitochondria maintain their own genome. Despite the discovery more than 50 y ago, still very little is known about how the genome is correctly segregated during cell division. The protozoan parasite Trypanosoma brucei contains a single mitochondrion with a singular genome, the kinetoplast DNA (kDNA). Electron microscopy studies revealed the tripartite attachment complex (TAC) to physically connect the kDNA to the basal body of the flagellum and to ensure correct segregation of the mitochondrial genome via the basal bodies movement, during the cell cycle. Using superresolution microscopy, we precisely localize each of the currently known TAC components. We demonstrate that the TAC is assembled in a hierarchical order from the base of the flagellum toward the mitochondrial genome and that the assembly is not dependent on the kDNA itself. Based on the biochemical analysis, the TAC consists of several nonoverlapping subcomplexes, suggesting an overall size of the TAC exceeding 2.8 mDa. We furthermore demonstrate that the TAC is required for correct mitochondrial organelle positioning but not for organelle biogenesis or segregation