Phenytoin-Induced Gingival Overgrowth: A Review of the Molecular, Immune, and Inflammatory Features

Gingival overgrowth (GO) is a side effect associated with some distinct classes of drugs, such as anticonvulsants, immunosuppressant, and calcium channel blockers. GO is characterized by the accumulation of extracellular matrix in gingival connective tissues, particularly collagenous components, with varying degrees of inflammation. One of the main drugs associated with GO is the antiepileptic phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. Nevertheless, the pathogenesis of such drug-induced GO remains fulfilled by some contradictory findings. This paper aims to present the most relevant studies regarding the molecular, immune, and inflammatory aspects of phenytoin-induced gingival overgrowth

The Inhibition of Phosphoinositide-3 Kinases Induce Resolution of Inflammation in a Gout Model

Phosphoinositide-3 kinases (PI3Ks) are central signaling enzymes that are involved in many aspects of immune cell function. PI3Kγ and PI3Kδ are the major isoforms expressed in leukocytes. The role of PI3K isoforms in the resolution of inflammation is still poorly understood. Here, we investigated the contribution of PI3Kγ and PI3Kδ to the resolution of inflammation in a model of gout in mice.Methods and Results: Experiments were performed in wild-type male C57/Bl6 mice. Selective inhibitors of PI3K-γ (AS605240) or PI3Kδ (GSK045) were injected in the joint 12 h after injection of MSU crystals, hence at the peak of inflammation. Inhibition of either PI3K isoform decreased number of neutrophils that migrated in response to the injection of MSU crystals. This was associated with reduction of myeloperoxidase activity and IL-1β levels in periarticular tissues and reduction of histological score. Joint dysfunction, as seen by reduced mechanical hypernociception, was improved by treatment with either inhibitor. The decrease in neutrophil numbers was associated with enhanced apoptosis and efferocytosis of these cells. There was shortening of resolution intervals, suggesting inhibition of either isoform induced the resolution of neutrophilic inflammation. Blockade of PI3Kγ or PI3Kδ reduced Nuclear Factor kappa B (NF-κB) activation. A pan-PI3K inhibitor (CL27c) reduced inflammation induced by MSU crystals by a magnitude that was similar to that attained by the PI3Kγ or PI3Kδ selective inhibitors alone.Conclusion: Taken together, these results suggest that neutrophils can use PI3Kγ or PI3Kδ to remain in the cavity and blockade of either isoenzyme is sufficient to induce their apoptosis and resolve inflammation in a murine model of gout

A Controversial Role for IL-12 in Immune Response and Bone Resorption at Apical Periodontal Sites

Periapical lesions are inflammatory conditions of tooth periapical tissues, triggered by dental pulp infection and characterized by exudation of immune cells to the affected tissues and production of inflammatory mediators such as cytokines. The inflammatory periapical reaction is mainly driven by Th1, Th2, and Th17 responses, and such polarization may modulate progression of the disease and expression of bone proresorptive cytokines. IL-12 is a potent inducer of IFN-γ production, which stimulates Th1 effector cells. Many evidences have shown a positive correlation between the bone resorptive cytokine IL-1β and the production of IL-12 and IFN-γ. Furthermore, IL-12 may have a potential role in the release of bone resorptive mediators and blockade of Th2 cytokines, affecting the progression of periapical bone loss. Nevertheless, IL-12 and IFN-γ have also been described as suppressors of osteoclast differentiation and activation, favoring bone maintenance. This paper focuses on the controversial roles of IL-12 in periapical lesions

SOCS2 Is Critical for the Balancing of Immune Response and Oxidate Stress Protecting Against Acetaminophen-Induced Acute Liver Injury

Acetaminophen (APAP) is usually safe when administrated in therapeutic doses; however, APAP overdose can lead to severe liver injury. APAP can cause direct hepatocyte damage, and stimulates an inflammatory response leading to oxidative stress. Supressor of Cytokine Signaling (SOCS) 2 modulates cytokine and growth factor signaling, and plays a role in the regulation of hepatic cellular processes. Our study evaluated the role of SOCS2 in APAP liver injury. The administration of a toxic dose (600 mg/kg) of APAP caused significant liver necrosis in WT mice. In SOCS2−/− mice, there was significantly more necrosis, neutrophil recruitment, and expression of the neutrophil-active chemokine CXCL-1. Expression of proinflammatory cytokines, such as TNF-α and IL-6, was elevated, while expression of anti-inflammatory cytokines, IL-10 and TGF-β, was diminished. In vitro, SOCS2−/− hepatocytes expressed more p-NF-kB and produced more ROS than WT hepatocytes when exposed to APAP. SOCS2−/− hepatocytes were more sensitive to cell death in the presence of IL-6 and hydrogen peroxide. The administration of catalase in vitro and in vivo resulted in a pronounced reduction of cells/mice death and necrosis in the SOCS2−/− group. We have demonstrated that SOCS2 has a protective role in the liver by controlling pro-oxidative and inflammatory mechanisms induced by APAP

Gut dysbiosis during influenza contributes to pulmonary pneumococcal superinfection through altered short-chain fatty acid production

Secondary bacterial infections often complicate viral respiratory infections. We hypothesize that perturbation of the gut microbiota during influenza A virus (IAV) infection might favor respiratory bacterial superinfection. Sublethal infection with influenza transiently alters the composition and fermentative activity of the gut microbiota in mice. These changes are attributed in part to reduced food consumption. Fecal transfer experiments demonstrate that the IAV-conditioned microbiota compromises lung defenses against pneumococcal infection. In mechanistic terms, reduced production of the predominant short-chain fatty acid (SCFA) acetate affects the bactericidal activity of alveolar macrophages. Following treatment with acetate, mice colonized with the IAV-conditioned microbiota display reduced bacterial loads. In the context of influenza infection, acetate supplementation reduces, in a free fatty acid receptor 2 (FFAR2)-dependent manner, local and systemic bacterial loads. This translates into reduced lung pathology and improved survival rates of double-infected mice. Lastly, pharmacological activation of the SCFA receptor FFAR2 during influenza reduces bacterial superinfection

O PERFIL DE SENSIBILIZAÇÃO ACERCA DO DESCARTE E REUTILIZAÇÃO DE RESÍDUOS SÓLIDOS NA CIDADE UNIVERSITÁRIA, UNIVERSIDADE FEDERAL DO MARANHÃO.

An important aspect the still absent in many universities is planning of disposal, storage and reuse of solid waste. The identification ofsituations faced by academic community regarding generation of waste is essential to the elaboration of programs, projects, systems andpolicies for sustainable management of generated waste. This study aimed to understand how aware of this issue is academic communityof the University City, Federal University of Maranhão (UFMA), through a profile of the production of solid waste and its impacts on theenvironment. The methodology was based on the application of 509 questionnaires during the year 2011 in four different campuses centers,including 33 undergraduate and graduate departments from various fields, and six administrative centers. The questionnaires consisted ofquestions about recycling policies and waste sorting. According to our results, 67.97 % of respondents know the 3Rs (reduce, reuse andrecycle) and 92.32 % said they would participate in a program for waste management if the university were to do so. However, over 60 % ofrespondents do not separate their household waste. Thus, it is important to note that, although encouraged by the university administration,an effective campaign should include the individual awareness of the academic body.Identificar situações com as quais a comunidade acadêmica se defronta quanto à geração de resíduos é imprescindível para que haja uma elaboração de programas e políticas de gestão sustentável em universidades. Este trabalho visou compreender como se dá a sensibilização da comunidade acadêmica da Cidade Universitária/ UFMA, acerca da produção de resíduos sólidos e seus devidos impactos ambientais. A metodologia baseou-se na aplicação de 509 questionários, com perguntas acerca de políticas de reciclagem e coleta seletiva, abrangendo 33 cursos de graduação e pós-graduação de diversas áreas e seis instâncias administrativas. De acordo com os resultados, 67,97% dos entrevistados conhecem as políticas de reaproveitamento, reutilização e reciclagem de resíduos e 92,32% afirmou que participaria de um programa interno caso houvesse incentivo para tal. Assim, é importante ressaltar que ainda que incentivado pelas instâncias administrativas, uma campanha efetiva deve incluir a sensibilização dos integrantes da comunidade acadêmica em questão