Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed

Chronotype and anxiety are associated in patients with chronic primary insomnia

Objective: To assess the interaction of chronotype with anxiety in patients with chronic primary insomnia. Methods: Sixty-four patients (50 women) with mean age 43.9 +/- 8.1 years were investigated with the Horne and Ostberg Morningness-Eveningness Questionnaire (MEQ) and State-Trait Anxiety Inventory (STAI). Results: Significant negative correlations of chronotype-MEQ score with STAI state-anxiety (r = -0.40, p < 0.05), STAI trait-anxiety (r = -0.40, p < 0.05), and STAI pre-sleep state anxiety (r = -0.30, p < 0.05) were observed. Eveningness preference was associated with higher trait, state, and pre-sleep state anxiety. Conclusions: These results suggest that chronotype may be an important parameter to identifying the origin and significance of a vicious anxiety-insomnia-depression cycle in patients with chronic primary insomnia.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Associação Fundo de Incentivo à Pesquisa (AFIP)Centro de Estudos em Psicobiologia e Exercicio (CEPE)Univ Fed Sao Paulo UNIFESP, Dept Psicobiol, Sao Paulo, SP, BrazilUniv Fed Goias UFG, Programa Mestrado Ciencias Aplicadas Saude, Jatai, Go, BrazilUniv Fed Minas Gerais, EEFFTO, Campus Pampulha, Belo Horizonte, MG, BrazilUniv Fed Sao Paulo UNIFESP, Dept Psicobiol, Sao Paulo, SP, BrazilFAPESP: 98/14303-3FAPESP: 2008/02862-1Web of Scienc

Functional complementation of Leishmania (Leishmania) amazonensis AP endonuclease gene (lamap) in Escherichia coli mutant strains challenged with DNA damage agents

During its life cycle Leishmania spp. face several stress conditions that can cause DNA damages. Base Excision Repair plays an important role in DNA maintenance and it is one of the most conserved mechanisms in all living organisms. DNA repair in trypanosomatids has been reported only for Old World Leishmania species. Here the AP endonuclease from Leishmania (L.) amazonensis was cloned, expressed in Escherichia coli mutants defective on the DNA repair machinery, that were submitted to different stress conditions, showing ability to survive in comparison to the triple null mutant parental strain BW535. Phylogenetic and multiple sequence analyses also confirmed that LAMAP belongs to the AP endonuclease class of proteins

Molecular approaches to trematode systematics: 'best practice' and implications for future study

To date, morphological analysis has been the cornerstone to trematode systematics. However, since the late-1980s we have seen an increased integration of genetic data to overcome problems encountered when morphological data are considered in isolation. Here, we provide advice regarding the ‘best molecular practice’ for trematode taxonomy and systematic studies, in an attempt to help unify the field and provide a solid foundation to underpin future work. Emphasis is placed on defining the study goals and recommendations are made regarding sample preservation, extraction methods, and the submission of molecular vouchers. We advocate generating sequence data from all parasite species/host species/geographic location combinations and stress the importance of selecting two independently evolving loci (one ribosomal and one mitochondrial marker). We recommend that loci should be chosen to provide genetic variation suitable to address the question at hand and for which sufficient ‘useful’ comparative sequence data already exist. Quality control of the molecular data via using proof-reading Taq polymerase, sequencing PCR amplicons using both forward and reverse primers, ensuring that a minimum of 85% overlap exists when constructing consensus sequences, and checking electropherograms by eye is stressed. We advise that all genetic results are best interpreted using a holistic biological approach, which considers morphology, host identity, collection locality, and ecology. Finally, we consider what advances next-generation sequencing holds for trematode taxonomy and systematics

Interações medicamentosas potenciais entre idosos em uso dos anti-hipertensivos da Relação Nacional de Medicamentos Essenciais do Ministério da Saúde do Brasil

O objetivo deste estudo foi estimar a prevalência de interações medicamentosas potenciais entre anti-hipertensivos e outros fármacos. Foi realizado um inquérito domiciliar com pessoas de 60 anos ou mais de idade, residentes no Rio de Janeiro, Brasil. Foram identificadas as interações medicamentosas potenciais entre os anti- hipertensivos com evidência estabelecida, provável ou suspeita e com gravidade moderada ou elevada. Foram entrevistados 577 idosos (média de idade = 72 anos), 45,2% dos quais em uso de anti-hipertensivos, sendo 31,0% deles sujeitos a interações medicamentosas potenciais. A maioria das interações foi moderadamente grave. Comparados aos demais, os sujeitos às interações medicamentosas potenciais têm chance acima de 4 vezes de usar 5 ou mais medicamentos e acima de duas vezes de ter sido hospitalizado no ano anterior. Entre os pares de interações mais frequentes, 75% produzem redução do efeito hipotensivo (65/87), o que pode resultar em baixa efetividade no controle da pressão arterial, prescrição de mais medicamentos e risco de outros efeitos adversos e de interações

Selenium Treatment and Chagasic Cardiopathy (STCC): study protocol for a double-blind randomized controlled trial

Background: Heart disease progression occurs in 30% of patients with chronic Trypanosoma cruzi infection. Supplementation with selenium (Se) in animal model of T. cruzi infection produced promising results. There is evidence that patients with Chagas heart disease have lower Se levels than healthy individuals and patients with T. cruzi infection without of cardiac disease. The aim of this investigation is to estimate the effect of Se treatment on prevention of heart disease progression in patients with chagasic cardiopathy. Methods: The Selenium Treatment and Chagasic Cardiopathy trial is a superiority, double-blind, placebo-controlled, randomized clinical trial. The eligibility criteria are as follows: (1) a Chagas disease diagnosis confirmed by serology; (2) segmental, mild or moderate global left ventricular systolic dysfunction; and (3) age between 18 and 65 years. The exclusion criteria are as follows: (1) pregnancy, (2) diabetes mellitus, (3) tobacco use, (4) alcohol abuse, (5) evidence of nonchagasic heart disease, (6) depression, (7) dysphagia with evidence of food residues in the esophagus, (8) dysphagia with weight loss higher than 15% of usual weight in the last four months and/or (9) conditions that may result in low protocol adherence. The intervention will be 100 μg of sodium selenite once daily for 365 consecutive days compared to placebo. The following are the primary outcomes to be measured: (1) the trajectories of the left ventricular ejection fraction in the follow-up period; (2) reduction of heart disease progression rates, with progression defined as a 10% decrease in left ventricular ejection fraction; and (3) rate of hospital admissions attributable to dysrhythmia, heart failure or stroke due to Chagas disease. One hundred thirty patients will be randomly allocated into either the intervention or placebo group at a ratio of 1:1. The sequence allocation concealment and blinding were planned to be conducted with the strategy of numbered boxes. Both patients and health-care providers will remain blinded to the intervention groups during the 5 years of follow-up. Discussion: If Se treatment reduces the progression of Chagas cardiopathy, the inclusion of this micronutrient in the daily diet can improve the therapeutic regimen for this neglected tropical disease at low cost

Lipid (per) oxidation in mitochondria:an emerging target in the ageing process?

Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation. In addition, senescent cells, which are known to contribute significantly to age-related pathologies, are also associated with impaired mitochondrial function and changes in lipid metabolism. Therapeutic targeting of dysfunctional mitochondrial and pathological lipid metabolism is an emerging strategy for alleviating their negative impact during ageing and the progression to age-related diseases. Such therapies could include the use of drugs that prevent mitochondrial uncoupling, inhibit inflammatory lipid synthesis, modulate lipid transport or storage, reduce mitochondrial oxidative stress and eliminate senescent cells from tissues. In this review, we provide an overview of lipid structure and function, with emphasis on mitochondrial lipids and their potential for therapeutic targeting during ageing and age-related disease