IMPORTÂNCIA DO CONTROLE MICROBIOLÓGICO DE ESPONJAS DE POLIURETANO COMO FERRAMENTA DE PROMOÇÃO DA SAÚDE INDIVIDUAL E COLETIVA

As esponjas de polietileno utilizadas durante as etapas de limpeza de equipamentos e utensílios podem, como consequência deste processo e da presença de poros em sua superfície, favorecer um crescimento rápido de micro-organismos. Neste sentido, muitas vezes podem ainda possibilitar uma contaminação cruzada desencadeada por bactérias, vírus e fungos através de alimentos infectados. Assim, os objetivos do presente trabalho foram divulgar as esponjas de poliuretano como um importante foco de retenção e de multiplicação de diversos micro-organismos através de uma revisão de Literatura nas bases de dados Scielo, Pubmed e LILACS, utilizando descritores específicos. Então, foi proferida uma palestra sócio-educativa para um grupo-alvo na cidade de Jequeri-MG. Sobre os resultados, diversas pesquisas revelaram que nas esponjas utilizadas nos processos de limpeza e desinfecção de superfícies, equipamentos e utensílios, são encontradas uma grande variedade de micro-organismos. Sendo expressivo o aumento de doenças transmitidas por alimentos (DTA’s) nos últimos anos a nível mundial. E mesmo com grandes esforços com prevenções, a contaminação cruzada é apontada como a principal causadora das DTA’s. Ainda, notou-se uma falta de conhecimento do público sobre o assunto, e de uma maior necessidade de disseminação de informações sobre o assunto, bem como a relevância de sua troca periódica

Bioética clínica e ensino-aprendizagem de estudantes de Farmácia: propostas do modelo deliberativo de Diego Gracia

In general, health care encompasses activities that demand safe clinical performance from pharmaceutical professionals. This performance considers the improved relationship with patients through attributes to deal with conflicting scenarios, the so-called “ethical-moral problems”. In this sense, Diego Gracia's deliberative method operates in the prudent democratic discussion of cases based on facts, values and duties, forming multidisciplinary committees. The study in question presents contributions from the application of the deliberative method in the classroom, with the approach of relevant problems for the pharmaceutical and human activity under the gaze of contemporary Bioethics worked together with students of the Pharmacy course of the 6th and 10th periods, respectively. Deliberation as a teaching strategy made it possible for students to reflect on the numerous perspectives in health decision-making, considering aspects such as culture, religion, and society; in addition, he highlighted the importance of subjects related to Deontology and Bioethics in the curriculum.En general, el cuidado de la salud engloba actividades que exigen un desempeño clínico seguro por parte de los profesionales farmacéuticos. Esta acción considera la mejora de la relación con los pacientes a través de atributos para enfrentar escenarios conflictivos, los denominados “problemas ético-morales”. En este sentido, el método deliberativo de Diego Gracia opera en la prudente discusión democrática de los casos a partir de hechos, valores y deberes, formando comités multidisciplinarios. El estudio en cuestión presenta aportes desde la aplicación del método deliberativo en el aula, con el abordaje de problemas relevantes para la actividad farmacéutica y humana bajo la mirada de la Bioética contemporánea trabajada junto a estudiantes de la carrera de Farmacia de los períodos 6° y 10°, respectivamente. La deliberación como estrategia de enseñanza posibilitó que los estudiantes reflexionaran sobre las múltiples perspectivas en la toma de decisiones en salud, considerando aspectos como la cultura, la religión y la sociedad; además, resaltó la importancia de las materias relacionadas con la Deontología y la Bioética en el plan de estudios.De maneira geral, a atenção em saúde engloba atividades que demandam dos profissionais farmacêuticos a atuação clínica segura. Essa atuação considera a relação aperfeiçoada com os pacientes por meio de atributos para lidar com cenários conflitantes, os chamados “problemas ético-morais”. Nesse sentido, o método deliberativo de Diego Gracia atua na discussão democrática prudente de casos com base em fatos, valores e deveres, formando comitês multiprofissionais. O estudo em questão apresenta contribuições da aplicação do método deliberativo em sala de aula, com a abordagem de problemas relevantes para a atividade farmacêutica e humana sob o olhar da Bioética contemporânea trabalhado em conjunto com discentes do curso de Farmácia dos 6o e 10o períodos, respectivamente. A deliberação como estratégia de ensino possibilitou a reflexão dos alunos quanto às inúmeras perspectivas na tomada de decisão em saúde, considerando aspectos como cultura, religião e sociedade; além disso, exaltou a importância das disciplinas concernentes à Deontologia e à Bioética na matriz curricular

Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD), protects against cocaine toxicity. URB597 (1.0 mg/kg) abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg) reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen) increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse

Neutrophil recruitment is inhibited by nicotinamide in experimental pleurisy in mice

Several emerging lines of evidence support an anti-inflammatory role for nicotinamide and other vitamin B components. However, the mechanisms underlying their activity remain unclear. In the present study, we investigated the ability of nicotinamide to inhibit both neutrophil recruitment in IL-8-, LTB(4)- or carrageenan-induced pleurisy in mice and the rolling and adherence of neutrophils. Nicotinamide inhibited IL-8-, LTB(4)- and carrageenan-induced neutrophil migration, KC production and carrageenan-induced neutrophil rolling and adherence. We propose that the effects of nicotinamide in inhibiting neutrophil recruitment in carrageenan-induced pleurisy may be due to the ability of nicotinamide to inhibit the action of IL-8 and LTB(4), decrease KC production, and inhibit early events that regulate leukocyte migration from blood vessels into tissue.status: publishe

Interleukin-4 deficiency protects mice from acetaminophen-induced liver injury and inflammation by prevention of glutathione depletion

OBJECTIVE: Interleukin-4 (IL-4) is a multifunctional cytokine involved in many diseases such as autoimmune hepatitis and idiosyncratic drug reactions. However, its role in acetaminophen (APAP)-induced liver injury remains unclear. Our objective was to evaluate the contribution of IL-4 to the pathogenesis of APAP-induced liver injury. METHODS: Balb/C (WT) and IL-4 knockout (IL-4(-/-)) mice were orally overdosed with APAP. After 24 h, survival percentage, biochemical and morphological markers of liver injury, and tissue inflammation were assessed. RESULTS: IL-4(-/-) mice were protected from APAP toxicity. Intravital confocal microscopy, tissue histology and serum ALT levels showed significantly less liver injury and inflammation than in the WT group, which may explain the increased survival rate of IL-4(-/-) mice. In addition, IL-4(-/-) mice had decreased production of tumor necrosis factor α, CXCL1 and interleukin-1β in the liver, but not in a remote site such as the lungs. Hepatic macrophage activation was markedly reduced in IL-4-deficient mice. In addition, glutathione depletion-a primary cause of APAP-mediated injury-was significantly attenuated in IL-4(-/-) mice. CONCLUSIONS: Taken together, our data demonstrate that IL-4(-/-) mice are protected from APAP-induced liver injury due to reduced depletion of glutathione, which prevented liver damage and tissue inflammation.status: publishe

Converging TLR9 and PI3Kgamma signaling induces sterile inflammation and organ damage

Toll-like receptor 9 (TLR9) and Phosphatidylinositol-3-kinase gamma (PI3Kγ) are very important effectors of the immune response, however, the importance of such crosstalk for disease development is still a matter of discussion. Here we show that PI3Kγ is required for immune responses in which TLR9 is a relevant trigger. We demonstrate the requirement of PI3Kγ for TLR9-induced inflammation in a model of CpG-induced pleurisy. Such requirement was further observed in inflammatory models where DNA sensing via TLR9 contributes to disease, such as silicosis and drug-induced liver injury. Using adoptive transfer, we demonstrate that PI3Kγ is important not only in leukocytes but also in parenchymal cells for the progression of inflammation. We demonstrate this crosstalk between TLR9 and PI3Kγ in vitro using human PBMCs. The inhibition of PI3Kγ in CpG-stimulated PBMCs resulted in reduction of both cytokine production and phosphorylated Akt. Therefore, drugs that target PI3Kγ have the potential to treat diseases mediated by excessive TLR9 signalling.status: publishe

Murine model to study brain, behavior and immunity during hepatic encephalopathy

AIM: To propose an alternative model of hepatic encephalopathy (HE) in mice, resembling the human features of the disease. METHODS: Mice received two consecutive intraperitoneal injections of thioacetamide (TAA) at low dosage (300 mg/kg). Liver injury was assessed by serum transaminase levels (ALT) and liver histology (hematoxylin and eosin). Neutrophil infiltration was estimated by confocal liver intravital microscopy. Coagulopathy was evaluated using prolonged prothrombin and partial thromboplastin time. Hemodynamic parameters were measured through tail cuff. Ammonia levels were quantified in serum and brain samples. Electroencephalography (EEG) and psychomotor activity score were performed to show brain function. Brain edema was evaluated using magnetic resonance imaging. RESULTS: Mice submitted to the TAA regime developed massive liver injury, as shown by elevation of serum ALT levels and a high degree of liver necrosis. An intense hepatic neutrophil accumulation occurred in response to TAA-induced liver injury. This led to mice mortality and weight loss, which was associated with severe coagulopathy. Furthermore, TAA-treated mice presented with increased serum and cerebral levels of ammonia, in parallel with alterations in EEG spectrum and discrete brain edema, as shown by magnetic resonance imaging. In agreement with this, neuropsychomotor abnormalities ensued 36 h after TAA, fulfilling several HE features observed in humans. In this context of liver injury and neurological dysfunction, we observed lung inflammation and alterations in blood pressure and heart rate that were indicative of multiple organ dysfunction syndrome. CONCLUSION: In summary, we describe a new murine model of hepatic encephalopathy comprising multiple features of the disease in humans, which may provide new insights for treatment.status: publishe

Hepatic DNA Deposition Drives Drug-Induced Liver Injury and Inflammation in Mice

UNLABELLED: Drug-induced liver injury (DILI) is an important cause of acute liver failure, with limited therapeutic options. During DILI, oncotic necrosis with concomitant release and recognition of intracellular content amplifies liver inflammation and injury. Among these molecules, self-DNA has been widely shown to trigger inflammatory and autoimmune diseases; however, whether DNA released from damaged hepatocytes accumulates into necrotic liver and the impact of its recognition by the immune system remains elusive. Here we show that treatment with two different hepatotoxic compounds (acetaminophen and thioacetamide) caused DNA release into the hepatocyte cytoplasm, which occurred in parallel with cell death in vitro. Administration of these compounds in vivo caused massive DNA deposition within liver necrotic areas, together with an intravascular DNA coating. Using confocal intravital microscopy, we revealed that liver injury due to acetaminophen overdose led to a directional migration of neutrophils to DNA-rich areas, where they exhibit an active patrolling behavior. DNA removal by intravenous DNASE1 injection or ablation of Toll-like receptor 9 (TLR9)-mediated sensing significantly reduced systemic inflammation, liver neutrophil recruitment, and hepatotoxicity. Analysis of liver leukocytes by flow cytometry revealed that emigrated neutrophils up-regulated TLR9 expression during acetaminophen-mediated necrosis, and these cells sensed and reacted to extracellular DNA by activating the TLR9/NF-κB pathway. Likewise, adoptive transfer of wild-type neutrophils to TLR9(-/-) mice reversed the hepatoprotective phenotype otherwise observed in TLR9 absence. CONCLUSION: Hepatic DNA accumulation is a novel feature of DILI pathogenesis. Blockage of DNA recognition by the innate immune system may constitute a promising therapeutic venue.status: publishe

Hepatic DNA deposition drives drug-induced liver injury and inflammation in mice

Drug-induced liver injury (DILI) is an important cause of acute liver failure with limited therapeutic options. During DILI, oncotic necrosis with concomitant release and recognition of intracellular content amplifies liver inflammation and injury. Amongst these molecules, self-DNA has been widely shown to trigger inflammatory and autoimmune diseases; however, whether DNA released from damaged hepatocytes accumulates into necrotic liver and the impact of its recognition by the immune system remains elusive. Here we showed that treatment with two different hepatotoxic compounds (acetaminophen and thioacetamide) caused DNA release into the hepatocyte cytoplasm, which occurred in parallel with cell death in vitro. Administration of these compounds in vivo caused massive DNA deposition within liver necrotic areas, together with an intravascular DNA coating. Using confocal intravital microscopy, we revealed that liver injury due to acetaminophen overdose led to a directional migration of neutrophils to DNA-rich areas, where they exhibit an active patrolling behavior. DNA removal by intravenous DNASE1 injection or ablation of TLR9-mediated sensing significantly reduced systemic inflammation, liver neutrophil recruitment and hepatotoxicity. Analysis of liver leukocytes by flow cytometry revealed that emigrated neutrophils upregulated TLR9 expression during acetaminophen-mediated necrosis, and these cells sensed and reacted to extracellular DNA by activating the TLR9/NF-κB pathway. Likewise, adoptive transfer of wild-type neutrophils to TLR9(-/-) mice reversed the hepatoprotective phenotype otherwise observed in TLR9 absence. Conclusion: We described that hepatic DNA accumulation is a novel feature of DILI pathogenesis and blockage of DNA recognition by the innate immune system may consist in a promising therapeutic venue