Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system

The immune response is essential for keeping an organism healthy and for defending it from different types of pathogens. It is a complex system that consists of a large number of components performing different functions. The adequate and controlled interaction between these components is necessary for a robust and strong immune response. There are, however, many factors that interfere with the way the immune response functions. Stress and ageing now consistently appear in the literature as factors that act upon the immune system in the way that is often damaging. This review focuses on the role of stress and ageing in altering the robustness of the immune response first separately, and then simultaneously, discussing the effects that emerge from their interplay. The special focus is on the psychological stress and the impact that it has at different levels, from the whole system to the individual molecules, resulting in consequences for physical health

Stress and breast cancer: from epidemiology to molecular biology

Stress exposure has been proposed to contribute to the etiology of breast cancer. However, the validity of this assertion and the possible mechanisms involved are not well established. Epidemiologic studies differ in their assessment of the relative contribution of stress to breast cancer risk, while physiological studies propose a clear connection but lack the knowledge of intracellular pathways involved. The present review aims to consolidate the findings from different fields of research (including epidemiology, physiology, and molecular biology) in order to present a comprehensive picture of what we know to date about the role of stress in breast cancer development

Magnetic susceptibility anisotropy of myocardium imaged by cardiovascular magnetic resonance reflects the anisotropy of myocardial filament α-helix polypeptide bonds

BACKGROUND: A key component of evaluating myocardial tissue function is the assessment of myofiber organization and structure. Studies suggest that striated muscle fibers are magnetically anisotropic, which, if measurable in the heart, may provide a tool to assess myocardial microstructure and function. METHODS: To determine whether this weak anisotropy is observable and spatially quantifiable with cardiovascular magnetic resonance (CMR), both gradient-echo and diffusion-weighted data were collected from intact mouse heart specimens at 9.4 Tesla. Susceptibility anisotropy was experimentally calculated using a voxelwise analysis of myocardial tissue susceptibility as a function of myofiber angle. A myocardial tissue simulation was developed to evaluate the role of the known diamagnetic anisotropy of the peptide bond in the observed susceptibility contrast. RESULTS: The CMR data revealed that myocardial tissue fibers that were parallel and perpendicular to the magnetic field direction appeared relatively paramagnetic and diamagnetic, respectively. A linear relationship was found between the magnetic susceptibility of the myocardial tissue and the squared sine of the myofiber angle with respect to the field direction. The multi-filament model simulation yielded susceptibility anisotropy values that reflected those found in the experimental data, and were consistent that this anisotropy decreased as the echo time increased. CONCLUSIONS: Though other sources of susceptibility anisotropy in myocardium may exist, the arrangement of peptide bonds in the myofilaments is a significant, and likely the most dominant source of susceptibility anisotropy. This anisotropy can be further exploited to probe the integrity and organization of myofibers in both healthy and diseased heart tissue

Análise microbiológica de gastroscópios descontaminados em aparelho Cleantop WM-1 por uso de água eletrolítica ácida Microbiological evaluation of gastroscope decontamination by electrolysed acid water (Clentop WM-1)

RACIONAL: O método com utilização manual de glutaraldeído é amplamente empregado para desinfecção de endoscópios. A elevada rotina nos serviços de gastroscopia, pequena quantidade de equipamentos e a falta de conhecimento técnico sobre os processos de descontaminação contribuem para desinfecção inadequada dos endoscópios, intensificando o risco de transmissão de microrganismos. A água eletrolítica ácida tem apresentado eficácia na inativação e destruição de microrganismos e vem sendo usada na descontaminação de endoscópios. OBJETIVO: Verificar a eficiência microbicida da água eletrolítica ácida, produzida pelo aparelho Cleantop WM-1, em 20 gastroscópios contaminados após uso em pacientes. MATERIAL E MÉTODOS: Amostras coletadas do canal de biopsia dos endoscópios, após uso em pacientes (n = 20) e depois da desinfecção (n = 20), foram cultivadas em ágar tripticaseína de soja, MacConkey e Sabouraud dextrose. RESULTADOS: Dezessete das 20 amostras coletadas após o uso do aparelho em pacientes revelaram a presença de bacilos gram-negativos, cocos gram-positivos e leveduras em taxas de 10³ a 10(5) ufc/mL. Nenhuma amostra, das 20 coletadas após a descontaminação, apresentou contaminação microbiana. CONCLUSÃO: Nesse estudo preliminar, a desinfecção mecânica realizada pelo aparelho Cleantop com água eletrolítica ácida revelou resultados satisfatórios pela eliminação de microrganismos e otimização no tempo de processamento dos gastroscópios<br>BACKGROUND: The manual disinfection of endoscopes with glutharaldeyde is widely employed. The great routine in gastroenteroscopy services, low number of equipment and the lack of technical knowledge about the decontamination processes are factors that stimulate the inadequate endoscope disinfection, intensifying the risk of transmission of microorganisms. The electrolysed acid water has been effective in the inactivation and destruction of microorganisms. AIM: The purpose of this investigation was to verify the microbicidal efficiency of electrolyzed acid water (Cleantop WM-1) to decontaminate gastroscopes after their using in patients. MATERIAL AND METHODS: Samples from biopsy channel of flexible endoscopes collected after patient use (n = 20) and after disinfection (n = 20) were cultivated in tryptic soy agar, MacConkey agar and Sabouraud dextrose agar. RESULTS: Seventeen of the 20 samples collected after patients examination yielded gram-negative bacilli, gram-positive coccus and yeast cells in contamination of 3 to 5 log10 ufc/mL. Microbial growth was not verified in samples collected after the decontamination process. Conclusion - In this preliminary study, the mechanical disinfection carried through the Cleantop device with electrolyzed acid water showed satisfactory results for the elimination of microorganisms and time optimization in the reprocessing of gastroscopes

Identification of a high affinity TAG-72 binding peptide by phage display selection

PURPOSE: Phage display was used to select novel peptides that specifically bind the TAG-72 antigen and with properties suitable for imaging TAG-72 positive cancers. RESULTS: After three rounds of selection against TAG-72 and using two different elution conditions including a long elution, the consensus sequences FRERCDKHPQKCTKFL and DPRHCQKRVLPCPAWL were expressed on phages G3-15 and T3-15 respectively. ELISA, fluorescence-activated cell sorting analysis and fluorescence microscopy provided evidence that both phages specifically bound TAG-72 in vitro. Both peptides are stable in 37oC serum. By a cell binding competition assay, the IC50 for T3-15 was measured as 0.29 nM and therefore 36-fold higher affinity than G3-15 at 10.32 nM. The biodistribution in mice carrying LS-174T tumors in one thigh were similar for both 99mTc-peptides at 30 min, but at 90 min the 99mTc-T3-15 peptide accumulated almost three times higher in the tumor. The SPECT/CT images were consistent with the biodistribution results. PROCEDURES: The f88-4/Cys6 phage library and two different elution conditions were used to identify two new higher affinity binding peptides for the TAG-72 antigen. One, was a single brief elution with pH 2.2 glycine buffer, and the second began with the glycine elution but was followed with a longer elution with Tris buffered saline (TBS) at pH 7.4. The phages that bound TAG-72 were evaluated by fluorescence-activated cell sorting analysis using TAG-72 positive LS-174T cells and confirmed by immunofluorescence imaging. The consensus peptides displayed on the selected phages were synthesized and conjugated with NHS-MAG3 for radiolabeling with 99mTc. The IC50 for TAG-72 binding was evaluated by cell binding competition in vitro while binding affinity was evaluated in vivo by necropsy and SPECT/CT imaging in a tumor mouse model. CONCLUSION: We have identified a peptide with a sub nanomolar inhibition constant for the TAG-72 antigen that may have application in cancer imaging