Protein kinase B (AKT) upregulation and Thy-1-αvß3 integrin-induced phosphorylation of Connexin43 by activated AKT in astrogliosis.

BACKGROUND: In response to brain injury or inflammation, astrocytes undergo hypertrophy, proliferate, and migrate to the damaged zone. These changes, collectively known as "astrogliosis", initially protect the brain; however, astrogliosis can also cause neuronal dysfunction. Additionally, these astrocytes undergo intracellular changes involving alterations in the expression and localization of many proteins, including αvß3 integrin. Our previous reports indicate that Thy-1, a neuronal glycoprotein, binds to this integrin inducing Connexin43 (Cx43) hemichannel (HC) opening, ATP release, and astrocyte migration. Despite such insight, important links and molecular events leading to astrogliosis remain to be defined. METHODS: Using bioinformatics approaches, we analyzed different Gene Expression Omnibus datasets to identify changes occurring in reactive astrocytes as compared to astrocytes from the normal mouse brain. In silico analysis was validated by both qRT-PCR and immunoblotting using reactive astrocyte cultures from the normal rat brain treated with TNF and from the brain of a hSOD1G93A transgenic mouse model. We evaluated the phosphorylation of Cx43 serine residue 373 (S373) by AKT and ATP release as a functional assay for HC opening. In vivo experiments were also performed with an AKT inhibitor (AKTi). RESULTS: The bioinformatics analysis revealed that genes of the PI3K/AKT signaling pathway were among the most significantly altered in reactive astrocytes. mRNA and protein levels of PI3K, AKT, as well as Cx43, were elevated in reactive astrocytes from normal rats and from hSOD1G93A transgenic mice, as compared to controls. In vitro, reactive astrocytes stimulated with Thy-1 responded by activating AKT, which phosphorylated S373Cx43. Increased pS373Cx43 augmented the release of ATP to the extracellular medium and AKTi inhibited these Thy-1-induced responses. Furthermore, in an in vivo model of inflammation (brain damage), AKTi decreased the levels of astrocyte reactivity markers and S373Cx43 phosphorylation. CONCLUSIONS: Here, we identify changes in the PI3K/AKT molecular signaling network and show how they participate in astrogliosis by regulating the HC protein Cx43. Moreover, because HC opening and ATP release are important in astrocyte reactivity, the phosphorylation of Cx43 by AKT and the associated increase in ATP release identify a potential therapeutic window of opportunity to limit the adverse effects of astrogliosis.

Extracapsular dissection and minimally invasive procedures of primary benign parotid tumours: Case series

Extracapsular dissection is an old technique use for the removal of benign parotid tumours, which is not generally chosen as the first treatment option due to the association of recurrences in the past but is currently considered again accord to the aesthetic requirements of the patients. The general trend in the last decade is to return to minimally invasive procedures for this type of lesions, which are mainly conditioned by the pleomorphic adenoma and its positive margins in its capsule. By this, the purpose of this case series study is to analyze those patients diagnosed with benign parotid tumors and treated by extracapsular dissection in a tertiary hospital in Chile between 2018-2020.

[Antimicrobial prophylaxis for transient bacteremia during dental procedures]. / Relevancia de profilaxis antibiótica ante procedimientos dentales generadores de bacteriemias transitorias.

This review examines the evidence about the relationship between dental procedures and the incidence of transient bacteremia. One of the main obstacles was to define "invasive dental procedure" as an indication for antimicrobial prophylaxis for patients with high risk of bacteremia. A search in WorldWideScience and ScienceDirect was performed and 20 articles were selected for review. Two contradictions stood out. There is no concrete evidence that a transient bacteremia arising during a dental procedure may be a risk factor for the appearance of bacterial endocarditis. There is no certainty about the effectiveness of antimicrobial prophylaxis, due to the lack of clinical trials of good quality. There is a similitude between bacteremia resulting from invasive and non-invasive dental procedures. The importance of periodontal health as a preventive measure for bacterial endocarditis among high risk patients is highlighted.

Relevancia de profilaxis antibiótica ante procedimientos dentales generadores de bacteriemias transitorias / Antimicrobial prophylaxis for transient bacteremia during dental procedures

This review examines the evidence about the relationship between dental procedures and the incidence of transient bacteremia. One of the main obstacles was to define "invasive dental procedure" as an indication for antimicrobial prophylaxis for patients with high risk of bacteremia. A search in WorldWideScience and ScienceDirect was performed and 20 articles were selected for review. Two contradictions stood out. There is no concrete evidence that a transient bacteremia arising during a dental procedure may be a risk factor for the appearance of bacterial endocarditis. There is no certainty about the effectiveness of antimicrobial prophylaxis, due to the lack of clinical trials of good quality. There is a similitude between bacteremia resulting from invasive and non-invasive dental procedures. The importance of periodontal health as a preventive measure for bacterial endocarditis among high risk patients is highlighted.

Osteonecrosis mandibular relacionada con medicamentos: conceptos teóricos y prácticos actuales para el odontólogo general

La osteonecrosis mandibular relacionada con medicamentos (ONMRM), es un síndrome asociado al uso de fármacos antirresortivos (bifosfonatos), inhibidores de ligando RANK-L y de angiogénesis, administrados para el tratamiento de enfermedades como cáncer y osteoporosis. Objetivos: actualizar contenidos respecto a etiopatogenia y tratamientos de ONMRM, enfatizando el rol del factor "infección", y en la perspectiva de que el tratamiento, pueda ser implementado por el odontólogo general. Materiales y métodos: se realiza un scoping review mediante acceso a las bases de datos MEDLINE (Pubmed) y Cochrane library, de artículos publicados desde el año 2010 en adelante, en inglés y castellano, empleando palabras claves incluidas en los medical subject headings (MeSH). Conclusiones: La evidencia recogida demuestra que, teniendo en cuenta los factores de riesgo individuales, no existen en general contraindicaciones para llevar a cabo exodoncias, bajo específicos protocolos quirúrgicos, en pacientes con terapias antiresortivas o antiangiogénicas, ya que al parecer, el origen de la ONMRM se asocia a contaminación por biofilm, más que al uso o efecto de estos fármacos. En el caso del tratamiento de una ONMRM ya instalada, las terapias quirúrgicas resultan ser más eficaces que las paliativas en la remisión del cuadro.

Medication-related osteonecrosis of the jaw (MRONJ) is a syndrome associated to the use of antiresorptive therapy (bisphosphonates), RANK-ligand inhibitors and angiogenesis inhibitors drugs, used for the treatment of cancer and osteoporosis among other diseases. Purpose: Update the knowledge on its etiopathogenesis emphasizing the role of infection, and in doing so, look for treatments that can be carried out by general practitioners. Materials and methods: A scoping review is performed through Medline (Pubmed) and Cochrane databases, of articles published from to 2010, in English and Spanish, including MeSH keywords such as "osteonecrosis of the jaw; "antiresorptive drug"; "bisphosphonates"; "Denosumab"; "surgical wound infection"; "dental extraction". Conclusions: The current evidence demonstrate that, taking into account individual risk factors, teeth extractions can be harmless performed in patients under antiresorptive or antiangiogenic interetherapies because the origin of MRONJ appears to be more related to biofilm contamination than with the use or effects of any specific drug. Once MRONJ is installed, surgical therapies prove to be more effective in the treatment and remission of these lesions.