Adenosine Diphosphate Improves Wound Healing in Diabetic Mice Through P2Y12 Receptor Activation.

Chronic wounds are a public health problem worldwide, especially those related to diabetes. Besides being an enormous burden to patients, it challenges wound care professionals and causes a great financial cost to health system. Considering the absence of effective treatments for chronic wounds, our aim was to better understand the pathophysiology of tissue repair in diabetes in order to find alternative strategies to accelerate wound healing. Nucleotides have been described as extracellular signaling molecules in different inflammatory processes, including tissue repair. Adenosine-5'-diphosphate (ADP) plays important roles in vascular and cellular response and is immediately released after tissue injury, mainly from platelets. However, despite the well described effect on platelet aggregation during inflammation and injury, little is known about the role of ADP on the multiple steps of tissue repair, particularly in skin wounds. Therefore, we used the full-thickness excisional wound model to evaluate the effect of local ADP application in wounds of diabetic mice. ADP accelerated cutaneous wound healing, improved new tissue formation, and increased both collagen deposition and transforming growth factor-ß (TGF-ß) production in the wound. These effects were mediated by P2Y12 receptor activation since they were inhibited by Clopidogrel (Clop) treatment, a P2Y12 receptor antagonist. Furthermore, P2Y1 receptor antagonist also blocked ADP-induced wound closure until day 7, suggesting its involvement early in repair process. Interestingly, ADP treatment increased the expression of P2Y12 and P2Y1 receptors in the wound. In parallel, ADP reduced reactive oxygen species (ROS) formation and tumor necrosis factor-α (TNF-α) levels, while increased IL-13 levels in the skin. Also, ADP increased the counts of neutrophils, eosinophils, mast cells, and gamma delta (γδ) T cells (Vγ4+ and Vγ5+ cells subtypes of γδ+ T cells), although reduced regulatory T (Tregs) cells in the lesion. In accordance, ADP increased fibroblast proliferation and migration, myofibroblast differentiation, and keratinocyte proliferation. In conclusion, we provide strong evidence that ADP acts as a pro-resolution mediator in diabetes-associated skin wounds and is a promising intervention target for this worldwide problem.

When fever is not malaria in Latin America: a systematic review.

BACKGROUND: In malaria-endemic countries, febrile episodes caused by diseases other than malaria are a growing concern. However, limited knowledge of the prevalent etiologic agents and their geographic distributions restrict the ability of health services to address non-malarial morbidity and mortality through effective case management. Here, we review the etiology of fever in Latin America (LA) between 1980 and 2015 and map significant pathogens commonly implicated in febrile infectious diseases. METHODS: A literature search was conducted, without language restrictions, in three distinct databases in order to identify fever etiology studies that report laboratory-confirmed fever-causing pathogens that were isolated from usually sterile body sites. Data analyses and mapping was conducted with Tableau Desktop (version 2018.2.3). RESULTS: Inclusion criteria were met by 625 publications corresponding to data relative to 34 countries. Studies using serology (n = 339) predominated for viral infections, culture (n = 131) for bacteria, and microscopy (n = 62) for fungi and parasites. The pathogen groups most frequently reported were viral infections (n = 277), bacterial infections (n = 265), parasitic infections (n = 59), fungal infections (n = 47), and more than one pathogen group (n = 24). The most frequently reported virus was dengue virus (n = 171), followed by other arboviruses (n = 55), and hantavirus (n = 18). For bacteria, Staphylococcus spp. (n = 82), Rickettsia spp. (n = 70), and Leptospira spp. (n = 55) were frequently reported. Areas with biggest gaps on etiology of fever were apparent. CONCLUSIONS: This review provides a landscape of pathogens causing febrile illness other than malaria in LA for over 30 years. Our findings highlight the need to standardize protocols and report guidelines for fever etiology studies for better comparability of results and improved interpretation. Lastly, we should improve existing national laboratory surveillance systems, especially from low- to middle-income countries, to inform global fever policy priorities and timely identify emerging infections threats. STUDY REGISTRATION: PROSPERO systematic review registration number: CRD42016049281.

Role of Chemokine Receptor CCR4 and Regulatory T Cells in Wound Healing of Diabetic Mice.

Wound healing is a well-coordinated process that involves inflammatory mediators and cellular responses; however, if any disturbances are present during this process, tissue repair is impaired. Chronic wounds are one of the serious long-term complications associated with diabetes mellitus. The chemokine receptor CCR4 and its respective ligands, CCL17 and CCL22, are involved in regulatory T cell recruitment and activation in inflamed skin; however, the role of regulatory T cells in wounds is still not clear. Our aim was to investigate the role of CCR4 and regulatory T cells in cutaneous wound healing in diabetic mice. Alloxan-induced diabetic wild- type mice (diabetic) developed wounds that were difficult to heal, differently from CCR4-/- diabetic mice (CCR4-/- diabetic), and also from anti-CCL17/22 or anti-CD25-injected diabetic mice that presented with accelerated wound healing and fewer regulatory T cells in the wound bed. Consequently, CCR4-/- diabetic mice also presented with alteration on T cells population in the wound and draining lymph nodes; on day 14, these mice also displayed an increase of collagen fiber deposition. Still, cytokine levels were decreased in the wounds of CCR4-/- diabetic mice on day 2. Our data suggest that the receptor CCR4 and regulatory T cells negatively affect wound healing in diabetic mice.

Memórias de Velhos: Rememorando a Trajetória de Vida e a Sociabilidade nas Relações Familiares / Elderly Memories: Recalling Life Trajectory and the Sociability in Family Relationships

O artigo tem por objetivo reconstruir, a partir da visão dos idosos, as suas impressões sobre as relações de sociabilidade e solidariedade da infância à velhice. Os dados foram coletados através de dezoito relatos pessoais. Os dados revelam a ocorrência de uma série de mudanças na vida dos idosos e da família, influenciadas pelos acontecimentos socioculturais, novas regulamentações do Estado em relação à sociedade e família e novas formas de proteção social.(AU)

This article aims at reconstructing from the perspective of the elderly, their impressions on the sociability and solidarity relations from childhood to old age. The data were collected from eighteen personal testimonies. The data reveal the occurrence of a series of changes in lives of the elderly and their families, influenced by socio-cultural events, new regulations of the State in relation to society and family and new ways of social protection.(AU)

Memórias de velhos: rememorando a trajetória de vida e a sociabilidade nas relações familiares / Elderly memories: recalling life trajectory and the sociability in family relationships

O artigo tem por objetivo reconstruir, a partir da visão dos idosos, as suas impressões sobre as relações de sociabilidade e solidariedade da infância à velhice. Os dados foram coletados através de dezoito relatos pessoais. Os dados revelam a ocorrência de uma série de mudanças na vida dos idosos e da família, influenciadas pelos acontecimentos socioculturais, novas regulamentações do Estado em relação à sociedade e família e novas formas de proteção social.

This article aims at reconstructing from the perspective of the elderly, their impressions on the sociability and solidarity relations from childhood to old age. The data were collected from eighteen personal testimonies. The data reveal the occurrence of a series of changes in lives of the elderly and their families, influenced by socio-cultural events, new regulations of the State in relation to society and family and new ways of social protection.

The effect and safety of dressing composed by nylon threads covered with metallic silver in wound treatment.

Silver is used worldwide in dressings for wound management. Silver has demonstrated great efficacy against a broad range of microorganisms, but there is very little data about the systemic absorption and toxicity of silver in vivo. In this study, the antimicrobial effect of the silver-coated dressing (SilverCoat(®)) was evaluated in vitro against the most common microorganisms found in wounds, including Pseudomonas aeruginosa, Candida albicans, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus and Klebsiella pneumoniae. We also performed an excisional skin lesion assay in mice to evaluate wound healing after 14 days of treatment with a silver-coated dressing, and we measured the amount of silver in the blood, the kidneys and the liver after treatment. Our data demonstrated that the nylon threads coated with metallic silver have a satisfactory antimicrobial effect in vitro, and the prolonged use of these threads did not lead to systemic silver absorption, did not induce toxicity in the kidneys and the liver and were not detrimental to the normal wound-healing process.

Cytotoxicity of PVPAC-treated bovine pericardium: a potential replacement for glutaraldehyde in biological heart valves.

Acellular biological tissues, including bovine pericardium (BP), have been proposed as biomaterial for tissue engineering. BP is usually modified chemically to improve mechanical and biological properties using glutaraldehyde, the standard reagent for preservation of fresh bioprosthetic materials. Glutaraldehyde-fixed BP (Glut-BP), the most widely used material in heart valve manufacture, has been associated with calcification in vivo. In an attempt to reduce this issue and maintain its biocompatibility, this study assesses the physical properties and cytotoxicity of lyophilized BP treated with poly (vinylpyrrolidone-co-acrolein) (PVPAC-BP), a novel copolymer, as a substitute for glutaraldehyde. For that, PVPAC-BP surface ultrastructure, elastic function, water uptake and tissue calcification were evaluated. For the analysis of biocompatibility, fibroblasts (3T3-L1) and endothelial cells (HUVEC) were cultured on PVPAC-BP, Untreated-BP and Glut-BP. Nitric oxide (NO) release assay, fluorescence and SEM images of endothelial cells adhered on scaffolds were also performed. As results, the data show some advantages of PVPAC-BP over the Glut-BP. The PVPAC-BP maintains partially the original ultrastructure and elastic properties, improves scaffold hydration, and presents less calcium phosphate deposits. The cells demonstrated strong attachment, high proliferation rate, and formation of a monolayer on PVPAC-BP. Attached cells were also able to release NO de-monstrating regular metabolism. In conclusion, PVPAC may be considered as a promising alternative to BP treatment improving the efficiency of cell attachment and proliferation and also avoid immunogenicity.

Protetores bucais e sua prevenção nos traumatismos dentais durante a prática esportiva

O presente estudo teve por objetivo analisar todos os aspectos referentes aos protetores bucais, desde sua eficácia, mecanismos de ação, vantagens e desvantagens, material usado...