Long-term tobacco exposure and immunosenescence: paradoxical effects on T-cells telomere length and telomerase activity

Immunosenescence are alterations on immune system that occurs throughout an individual life. The main characteristic of this process is replicative senescence, evaluated by telomere shortening. Several factors implicate on telomere shortening, such as smoking. In this study, we evaluated the influence of smoking and Chronic Obstructive Pulmonary Disease (COPD) on cytokines, telomere length and telomerase activity. Blood samples were collected from subjects aged over 60 years old: Healthy (never smokers), Smokers (smoking for over 30 years) and COPDs (ex-smokers for ≥15 years). A young group was included as control. PBMCs were cultured for assessment of telomerase activity using RT-PCR, and cytokines secretion flow cytometry. CD4+ and CD8+ purified lymphocytes were used to assess telomere length using FlowFISH. We observed that COPD patients have accelerated telomere shortening. Paradoxically, smokers without lung damage showed preserved telomere length, suggesting that tobacco smoking may affect regulatory mechanisms, such as telomerase. Telomerase activity showed diminished activity in COPDs, while Smokers showed increased activity compared to COPDs and Healthy groups. Extracellular environment reflected this unbalance, indicated by an anti-inflammatory profile in Smokers, while COPDs showed an inflammatory prone profile. Further studies focusing on telomeric maintenance may unveil mechanisms that are associated with cancer under long-term smoking

Lipidic characterization of Santa Ines lamb shoulder

The edible portion of the shoulder of 12 castrated and 12 non-castrated Santa Ines lambs slaughtered at different ages (84, 168, 210, 252 days) were used. The shoulders were chemically analyzed to determine the quantity of total lipids, cholesterol, and fatty acids composition. Castrated and non-castrated lambs gained body weight (p = 0.0393, p = 0.0017) and half carcass weight (p = 0.0240, p = 0.0017), respectively. The shoulder weight was increased in the carcasses of non-castrated lambs (p = 0.0110). The edible portion of the shoulder of castrated lambs presented higher total lipids (16.09 g.100 g(-1)). The cholesterol content was influenced by castration (p = 0.0001) reducing with age. Castrated animals presented higher content of C18:1 T11, CLA, and C18:0. The shoulder weight is only increased with increasing age in the carcasses of non-castrated lambs. Castration influences the cholesterol content of the shoulder; however, both castrated and non-castrated lambs had their cholesterol contents reduced with increasing age. Castration and age interfered in the estearic acid concentration of the edible portion of lamb shoulder.31250851

Field Theory for a Deuteron Quantum Liquid

Based on general symmetry principles we study an effective Lagrangian for a neutral system of condensed spin-1 deuteron nuclei and electrons, at greater-than-atomic but less-than-nuclear densities. We expect such matter to be present in thin layers within certain low-mass brown dwarfs. It may also be produced in future shock-wave-compression experiments as an effective fuel for laser induced nuclear fusion. We find a background solution of the effective theory describing a net spin zero condensate of deuterons with their spins aligned and anti-aligned in a certain spontaneously emerged preferred direction. The spectrum of low energy collective excitations contains two spin waves with linear dispersions -- like in antiferromagnets -- as well as gapped longitudinal and transverse modes related to the Meissner effect -- like in superconductors. We show that counting of the Nambu-Goldstone modes of spontaneously broken internal and space-time symmetries obeys, in a nontrivial way, the rules of the Goldstone theorem for Lorentz non-invariant systems. We discuss thermodynamic properties of the condensate, and its potential manifestation in the low-mass brown dwarfs.Comment: 19 LaTeX pages; v2: 2 refs added, JHEP versio

Rede de cuidado em saúde mental: visão dos coordenadores da estratégia saúde da família

RESUMO Objetivo Objetivou-se analisar a visão de coordenadores da Estratégia Saúde da Família (ESF) sobre a conformação da rede de saúde mental no município de Pelotas/RS. Método Estudo descritivo e exploratório, com abordagem qualitativa, realizado com seis coordenadores de ESF no ano de 2012. Para a coleta dos dados, foi utilizada a entrevista semiestruturada, e os resultados foram avaliados por análise temática. Resultados A rede construída pelos coordenadores é composta por poucos serviços formais e focada no Centro de Atenção Psicossocial (CAPS), e a rede informal é descrita com maiores pontos de cuidado. As trocas de corresponsabilidade no cuidado em rede ocorrem de forma frágil, sem o diálogo necessário. Conclusão Os coordenadores demonstram pouco conhecimento da rede formal de cuidado e uma atenção focada nos serviços da ESF e no CAPS. Reconhecem a importância de haver políticas públicas que valorizem e ampliem os espaços informais de cuidado no território

Microbiome-derived antimicrobial peptides offer therapeutic solutions for the treatment of Pseudomonas aeruginosa infections

Microbiomes are rife for biotechnological exploitation, particularly the rumen microbiome, due to their complexicity and diversity. In this study, antimicrobial peptides (AMPs) from the rumen microbiome (Lynronne 1, 2, 3 and P15s) were assessed for their therapeutic potential against seven clinical strains of Pseudomonas aeruginosa. All AMPs exhibited antimicrobial activity against all strains, with minimum inhibitory concentrations (MICs) ranging from 4–512 µg/mL. Time-kill kinetics of all AMPs at 3× MIC values against strains PAO1 and LES431 showed complete kill within 10 min to 4 h, although P15s was not bactericidal against PAO1. All AMPs significantly inhibited biofilm formation by strains PAO1 and LES431, and induction of resistance assays showed no decrease in activity against these strains. AMP cytotoxicity against human lung cells was also minimal. In terms of mechanism of action, the AMPs showed affinity towards PAO1 and LES431 bacterial membrane lipids, efficiently permeabilising the P. aeruginosa membrane. Transcriptome and metabolome analysis revealed increased catalytic activity at the cell membrane and promotion of β-oxidation of fatty acids. Finally, tests performed with the Galleria mellonella infection model showed that Lynronne 1 and 2 were efficacious in vivo, with a 100% survival rate following treatment at 32 mg/kg and 128 mg/kg, respectively. This study illustrates the therapeutic potential of microbiome-derived AMPs against P. aeruginosa infections

DETERMINATION OF VIRAL TROPISM BY GENOTYPING AND PHENOTYPING ASSAYS IN BRAZILIAN HIV-1-INFECTED PATIENTS

The clinical application of CCR5 antagonists involves first determining the coreceptor usage by the infecting viral strain. Bioinformatics programs that predict coreceptor usage could provide an alternative method to screen candidates for treatment with CCR5 antagonists, particularly in countries with limited financial resources. Thus, the present study aims to identify the best approach using bioinformatics tools for determining HIV-1 coreceptor usage in clinical practice. Proviral DNA sequences and Trofile results from 99 HIV-1-infected subjects under clinical monitoring were analyzed in this study. Based on the Trofile results, the viral variants present were 81.1% R5, 21.4% R5X4 and 1.8% X4. Determination of tropism using a Geno2pheno[coreceptor] analysis with a false positive rate of 10% gave the most suitable performance in this sampling: the R5 and X4 strains were found at frequencies of 78.5% and 28.4%, respectively, and there was 78.6% concordance between the phenotypic and genotypic results. Further studies are needed to clarify how genetic diversity amongst virus strains affects bioinformatics-driven approaches for determining tropism. Although this strategy could be useful for screening patients in developing countries, some limitations remain that restrict the wider application of coreceptor usage tests in clinical practice

Free Rhodium (II) citrate and rhodium (II) citrate magnetic carriers as potential strategies for breast cancer therapy

<p>Abstract</p> <p>Background</p> <p>Rhodium (II) citrate (Rh₂(H₂cit)₄) has significant antitumor, cytotoxic, and cytostatic activity on Ehrlich ascite tumor. Although toxic to normal cells, its lower toxicity when compared to carboxylate analogues of rhodium (II) indicates Rh₂(H₂cit)₄as a promising agent for chemotherapy. Nevertheless, few studies have been performed to explore this potential. Superparamagnetic particles of iron oxide (SPIOs) represent an attractive platform as carriers in drug delivery systems (DDS) because they can present greater specificity to tumor cells than normal cells. Thus, the association between Rh₂(H₂cit)₄and SPIOs can represent a strategy to enhance the former's therapeutic action. In this work, we report the cytotoxicity of free rhodium (II) citrate (Rh₂(H₂cit)₄) and rhodium (II) citrate-loaded maghemite nanoparticles or magnetoliposomes, used as drug delivery systems, on both normal and carcinoma breast cell cultures.</p> <p>Results</p> <p>Treatment with free Rh₂(H₂cit)₄induced cytotoxicity that was dependent on dose, time, and cell line. The IC₅₀values showed that this effect was more intense on breast normal cells (MCF-10A) than on breast carcinoma cells (MCF-7 and 4T1). However, the treatment with 50 μM Rh₂(H₂cit)₄-loaded maghemite nanoparticles (Magh-Rh₂(H₂cit)₄) and Rh₂(H₂cit)₄-loaded magnetoliposomes (Lip-Magh-Rh₂(H₂cit)₄) induced a higher cytotoxicity on MCF-7 and 4T1 than on MCF-10A (p < 0.05). These treatments enhanced cytotoxicity up to 4.6 times. These cytotoxic effects, induced by free Rh₂(H₂cit)₄, were evidenced by morphological alterations such as nuclear fragmentation, membrane blebbing and phosphatidylserine exposure, reduction of actin filaments, mitochondrial condensation and an increase in number of vacuoles, suggesting that Rh₂(H₂cit)₄induces cell death by apoptosis.</p> <p>Conclusions</p> <p>The treatment with rhodium (II) citrate-loaded maghemite nanoparticles and magnetoliposomes induced more specific cytotoxicity on breast carcinoma cells than on breast normal cells, which is the opposite of the results observed with free Rh₂(H₂cit)₄treatment. Thus, magnetic nanoparticles represent an attractive platform as carriers in Rh₂(H₂cit)₄delivery systems, since they can act preferentially in tumor cells. Therefore, these nanopaticulate systems may be explored as a potential tool for chemotherapy drug development.</p

Familial congenital cyanosis caused by Hb-MYantai(α-76 GAC → TAC, Asp → Tyr)

Methemoglobin (Hb-M) is a rare hemoglobinopathy in China. We hereby report on a family living in Yantai, East China, with congenital cyanosis due to Hb-M mutation. The proband, a 65-year-old female, presented 63% oxygen saturation. Both Hb-M concentration and arterial oxygen saturation remained unchanged, even following intravenous treatment with methylene blue. There was also no change in blood-color (chocolate-brown) after adding 0.1% KCN. A fast-moving band (Hb-X) in hemolysates was found by cellulose acetate electrophoresis, the Hb-X/Hb-A ratio exceeding 10%. GT transition at 131nt of exon 2, although present in one of the α2 -globin alleles, was not found in α1 -globin alleles as a whole. This mutation leads to the aspartic acid to tyrosine substitution (Asp76Tyr). In this family, the novel mutation in the α2 -globin gene resulted in a rare form of congenital cyanosis due to Hb-M. This hemoglobin was named Hb-M Yantai

Primary healthcare and the construction of thematic health networks: what role can they play?

The enhancement of primary healthcare has been a core strategy for the empowerment of the Brazilian Unified Health System (SUS). Recent guidelines issued by OPAS and the Ministry of Health highlight the role it has played as a thematic communication network center, a regulating agent for the access and use of services required for comprehensive healthcare. Sponsored by PPSUS/Fapesp, this study examines the possibilities of the primary healthcare network exercising such a strategic function. Life narratives involving 15 regular users were produced in two cities of ABC Paulista, which have adopted the Family Health Strategy for the organization of their primary healthcare networks. The study presents three main findings: the primary healthcare network serves as an outpost of SUS by producing user values even for high complexity service users; the primary network is perceived is a place for simple care needs; there is shared impotence between users and teams when it comes to the network functioning as the coordinator of care, indicating that it does not possess the technological, operational and organizational material conditions or symbolic conditions (values, meanings, and representations) to be in a central position in the coordination of thematic healthcare networks.O fortalecimento da atenção básica tem sido valorizado como estratégia central para a construção do SUS. Diretrizes recentes emanadas pela OPAS e pelo MS destacam seu papel como centro de comunicação de redes temáticas, como reguladora do acesso e utilização dos serviços necessários para a integralidade do cuidado. O presente estudo, financiado com recursos PPSUS/Fapesp, problematiza as possibilidades da rede básica exercer tal função estratégica. Foram produzidas narrativas de vida de 15 usuários altamente utilizadores de serviços de saúde em dois municípios do ABC paulista, que adotaram a Estratégia de Saúde da Família para organização de suas redes básicas. O estudo apresenta três achados principais: a rede básica funciona como posto avançado do SUS, produzindo valores de uso mesmo para os pacientes utilizadores de serviços de alta complexidade; a rede básica é vista como lugar de coisas simples; há uma impotência compartilhada entre usuários e equipes quando se trata da rede básica funcionar como coordenadora do cuidado, indicando como ela não reúne condições materiais (tecnológicas, operacionais, organizacionais) e simbólicas (valores, significados e representações) de deter a posição central da coordenação das redes temáticas de saúde.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Medicina PreventivaInstituto Superior de Ciências do Trabalho e da Empresa Instituto Universitário de Lisboa Faculdade de Ciências Médicas Departamento de Saúde ColetivaUniversidade Estadual de Campinas Faculdade de Ciências Médicas Departamento de Saúde ColetivaUNIFESP, EPM, Depto. de Medicina PreventivaSciEL