Cytosolic persistence of mouse brain CYP1A1 in chronic heme deficiency

Previous work has demonstrated that the function of extrahepatic cytochrome P450 CYP1A1 is dependent on the availability of heme. CYP1A1 is involved in the activation of polyaromatic hydrocarbons. In the present study we used a transgenic mouse model with chronic impairment of heme synthesis - female porphobilinogen deaminase-deficient (PBGD-/-) mice - to investigate the effects of limited heme in untreated and β-naphthoflavone (β-NF)-treated animals on the function of CYP1A1 in brain. The heme content of PBGD-/- mice was diminished in the liver and brain compared to wild types. In the liver, partial heme deficiency led to less potent induction of CYP1A1 mRNA after β-NF treatment. In the brain, CYP1A1 protein was detected not only at the endoplasmic reticulum (ER), but also in the cytosol of PBGD-/- mice. Furthermore, 7-deethylation of ethoxyresorufin, an indicator of CYP1A1 metabolic activity, could be restored by heme in cytosol of PBGD-/- mouse brain. Independent of the genotype, we found only one cyp1a1 gene product, indicating that the cytosolic appearance of CYP1A1 most likely did not originate from mutant alleles. We conclude that heme deficiency in the brain leads to incomplete heme saturation of CYP1A1, which causes its improper incorporation into the ER membrane and persistence in the cytosol. It is suggested that diseases caused by relative heme deficiency, such as hepatic porphyrias, may lead to impaired hemoprotein function in brai

Staging and resilience degree in breast cancer survivors

Objective: To assess the resilience and staging degree relating to sociodemographic factors of breast cancer survivors followed up in an oncology service. Method: Quantitative study with 112 breast cancer survivors. The variables selected were: sociodemographic; clinical staging; survival time; and resilience scale. The analysis was performed using the Epi Info 6.04 software and Fisher's exact test. The research was approved by the Ethics Committee of the Federal University of Pelotas School of Nursing under Opinion Nº 31/2009. Results: The average age was 46,2 years, there was 60,71% of stage II cases, 81,25% were white, 40,18% had five-to eight-year schooling, 52,68% were married, 73,32% had lived in urban areas, 41,96% exhibited high resilience, and 48,21% were followed up from one to three years. Conclusion: Staging was not associated with the resilience degree, but rather with age and survival time, confirming the findings of other studies

Staging and resilience degree in breast cancer survivors

Objective: To assess the resilience and staging degree relating to sociodemographic factors of breast cancer survivors followed up in an oncology service. Method: Quantitative study with 112 breast cancer survivors. The variables selected were: sociodemographic; clinical staging; survival time; and resilience scale. The analysis was performed using the Epi Info 6.04 software and Fisher's exact test. The research was approved by the Ethics Committee of the Federal University of Pelotas School of Nursing under Opinion Nº 31/2009. Results: The average age was 46,2 years, there was 60,71% of stage II cases, 81,25% were white, 40,18% had five-to eight-year schooling, 52,68% were married, 73,32% had lived in urban areas, 41,96% exhibited high resilience, and 48,21% were followed up from one to three years. Conclusion: Staging was not associated with the resilience degree, but rather with age and survival time, confirming the findings of other studies

Antimyelin antibodies in clinically isolated syndromes correlate with inflammation in MRI and CSF

Objective: We investigated the correlation of anti-myelin oligodendrocyte glycoprotein- (anti-MOG) and anti-myelin basic protein antibodies (anti-MBP) in serum of CIS patients with inflammatory signs in MRI and in CSF and, as previously suggested, the incidence of more frequent and rapid progression to clinically definite MS (CDMS). Methods: 133 CIS patients were analysed for anti-MOG and anti-MBP (Western blot). Routine CSF and cranial MRI (quantitatively and qualitatively) measures were analyzed. 55 patients had a follow-up of at least 12 months or until conversion to CDMS. Results: Patients with anti-MOG and anti-MBP had an increased intrathecal IgG production and CSF white blood cell count (p = 0.048 and p = 0.036). When anti-MBP alone, or both antibodies were present the cranial MRI showed significantly more T2 lesions (p = 0.007 and p = 0.01, respectively). There was a trend for more lesion dissemination in anti-MBP positive patients (p = 0.076). Conversely, anti-MOG- and/or anti-MBP failed to predict conversion to CDMS in our follow-up group (n = 55). Only in female patients with at least one MRI lesion (n = 34) did the presence of anti-MOG correlate with more frequent (p = 0.028) and more rapid (p = 0.0209) transition to CDMS. Conclusions: Presence of anti-MOG or anti-MBP or both was not significantly associated with conversion to CDMS in our CIS cohort. However, patients with anti-MOG and anti-MBP had higher lesion load and more disseminated lesions in cranial MRI as well as higher values for CSF leucocytes and intrathecal IgG production. Our data support a correlation of anti-MOG and anti-MBP to inflammatory signs in MRI and CSF. The prognostic value of these antibodies for CDMS, however, seems to be less pronounced than previously reporte

Neutralizing antibodies against IFN‐β in multiple sclerosis: antagonization of IFN‐β mediated suppression of MMPs

Neutralizing antibodies (NAb) against interferon‐β (IFN‐β) develop in about a third of treated multiple sclerosis patients and are believed to reduce therapeutic efficacy of IFN‐β on clinical and MRI measures. The expression of the interferon acute‐response protein, myxovirus resistance protein A (MxA) is a sensitive measure of the biological activity of therapeutically applied IFN‐β and of its reduced bioavailability due to NAb. However, MxA may not be operative in the pathogenesis of multiple sclerosis or the therapeutic effect of IFN‐β. Instead, matrix metalloproteinases (MMPs) are increased in brain tissue, CSF and blood circulation of multiple sclerosis patients and function as effector molecules in several steps of multiple sclerosis pathogenesis. One of the molecular mechanisms by which IFN‐β exerts its beneficial effect in multiple sclerosis is reduction of MMP‐9 expression and increase of its endogenous tissue inhibitor, TIMP‐1. Quantitative PCR measurements of MMP‐2 and MMP‐9, TIMP‐1 and TIMP‐2, and MxA were performed in peripheral mononuclear cells from clinically stable multiple sclerosis patients with relapsing remitting disease course after short‐term and long‐term treatment with IFN‐β. IFN‐β therapy down‐regulated the expression of MMP‐9 and abolished that of MMP‐2 in long‐term, but not short‐term treated multiple sclerosis, while levels of MxA were increased in both instances. The presence of NAb reversed these effects, i.e. led to reduced MxA and increased MMP‐2/MMP‐9 expression levels compared with NAb- patients. In contrast, expression of TIMPs in peripheral blood mononuclear cells remained unaffected by IFN‐β therapy and the presence of NAb. While MxA is able to detect the biological action and reduced bioavailability of IFN‐β on the basis of single injections, only MMP‐9 shows quantitative correlation with the NAb titre. Together with evidence that an imbalance between MMP and TIMP expression is a crucial pathogenetic feature in multiple sclerosis, these findings support the concept of a significant role of NAb in reducing the therapeutic efficacy of IFN‐

Estadiamento e grau de resiliência do sobrevivente ao câncer de mama Staging and resilience degree in breast cancer survivors

Objetivo: Investigar o grau de resiliência e de estadiamento frente aos fatores sociodemográficos dos sobreviventes ao câncer de mama em acompanhamento em um serviço de oncologia. Métodos: Estudo quantitativo, amostra de 112 sobreviventes ao câncer de mama. Foram selecionadas variáveis sociodemográficas, estadiamento clínico, tempo de sobrevida e escala de resiliência. Análise no epi-info 6.04 e teste exato de fischer. Aprovação do Comitê de Ética da Faculdade de Enfermagem da UFPel  nº 31/2009. Resultados: média de idade de 46,2 anos, 60,71% estadiamento II, 81,25% eram brancas, 40,18% com escolaridade entre 5-8 anos, 52,68% casados, 73,32% viveu em zona urbana, 41,96% apresentou alta resiliência e 48,21% mantinha-se em acompanhamento entre 1-3 anos. Conclusão: O estadiamento não está associado ao grau de resiliência, mas sim à idade e tempo de sobrevida confirmando os achados em outros estudos

Estadiamento e grau de resiliência do sobrevivente ao câncer de mama Staging and resilience degree in breast cancer survivors

Objetivo: Investigar o grau de resiliência e de estadiamento frente aos fatores sociodemográficos dos sobreviventes ao câncer de mama em acompanhamento em um serviço de oncologia. Métodos: Estudo quantitativo, amostra de 112 sobreviventes ao câncer de mama. Foram selecionadas variáveis sociodemográficas, estadiamento clínico, tempo de sobrevida e escala de resiliência. Análise no epi-info 6.04 e teste exato de fischer. Aprovação do Comitê de Ética da Faculdade de Enfermagem da UFPel  nº 31/2009. Resultados: média de idade de 46,2 anos, 60,71% estadiamento II, 81,25% eram brancas, 40,18% com escolaridade entre 5-8 anos, 52,68% casados, 73,32% viveu em zona urbana, 41,96% apresentou alta resiliência e 48,21% mantinha-se em acompanhamento entre 1-3 anos. Conclusão: O estadiamento não está associado ao grau de resiliência, mas sim à idade e tempo de sobrevida confirmando os achados em outros estudos

Resíduos sólidos, mais que uma Questão Ambiental, uma Questão Social

Este Trabalho visa relatar a experiência e os conhecimentos obtidos sobre o gerenciamento de resíduos sólidos, a partir de  um diagnóstico realizado no Instituto Federal de Educação Ciência e Tecnologia de Mato Grosso (IFMT - CAMPUS CUIABÁ),  Campus Octayde Jorge da Silva. O projeto de extensão contou com apoio financeiro do CNPq, Chamada CNPq/VALE S.A. Nº 05/2012 - Forma-Engenharia, projeto nº 454837/2012-7 e  integrou o Projeto Gestão dos Recursos Hídricos e Resíduos sólidos. Este projeto teve duração de 14 meses e foi dividido em três etapas. Na primeira etapa foi realizado o levantamento das  normas técnicas relativas a resíduos sólidos. Na segunda foi feito o diagnóstico da produção de resíduos sólidos na Instituição, tanto no quesito qualidade, quanto no quesito quantidade. Na terceira etapa realizou-se a análise das informações e  o desenvolvimento de algumas técnicas de educação ambiental com o intuito de contribuir na conscientização dos frequentadores do IFMT - CAMPUS CUIABÁ. Durante o desenvolvimento da pesquisa notaram-se várias irregularidades com relação ao armazenamento e o destino dos resíduos sólidos produzidos na Instituição. Os dados levantados, assim como as medidas tomadas com o intuito de minimizar os problemas que apareceram de forma cotidiana no Campus serão apresentados ao longo do artigo. Observou-se que as ações de educação ambiental adotadas não surtiram o efeito esperado junto à comunidade da instituição avaliada, talvez devido ao tempo curto ou à forma de abordagem. O artigo traz um breve relato sobre a importância da reciclagem dos resíduos sólidos na área da construção civil, inclusive analisando a visita à Eco Ambiental, empresa responsável pelo recolhimento e pela reciclagem de todos os resíduos sólidos referentes à construção civil da grande Cuiabá

Origin and Global Expansion of Mycobacterium tuberculosis Complex Lineage 3

Tuberculosis still causes 1.5 million deaths annually and is mainly caused by Mycobacterium tuberculosis complex strains belonging to three evolutionary modern lineages (Lineages 2–4). While Lineage 2 and Lineage 4 virtually conquered the world, Lineage 3 is particularly successful in Northern and Eastern Africa, as well as in Southern Asia, the suspected evolutionary origin of these strains. Here, we sought to understand how Lineage 3 strains came to the African continent. To this end, we performed routine genotyping to characterize over 2500 clinical isolates from 38 countries. We then selected a representative collection of 373 isolates for a whole-genome analysis and a modeling approach to infer the geographic origin of different sublineages. In fact, the origin of Lineage 3 could be located in India, and we found evidence for independent introductions of four distinct sublineages into North/East Africa, in line with known ancient exchanges and migrations between both world regions. Our study illustrates that the evolutionary history of humans and their pathogens are closely connected and further provides a systematic understanding of the genomic diversity of Lineage 3, which could be important for the development of new tuberculosis vaccines or new therapeutics.Mycobacterium tuberculosis complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global diversity of this major lineage, we analyzed a dataset comprising 2682 L3 strains from 38 countries over 5 continents, by employing 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping (MIRU-VNTR) and drug susceptibility testing. We further combined whole-genome sequencing (WGS) and phylogeographic analysis for 373 strains representing the global L3 genetic diversity. Ancestral state reconstruction confirmed that the origin of L3 strains is located in Southern Asia and further revealed multiple independent introduction events into North-East and East Africa. This study provides a systematic understanding of the global diversity of L3 strains and reports phylogenetic variations that could inform clinical trials which evaluate the effectivity of new drugs/regimens or vaccine candidates.Peer Reviewe