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.

Dietary supplementation with omega-3-PUFA-rich fish oil reduces signs of food allergy in ovalbumin-sensitized mice.

We investigated the effect of dietary supplementation with n-3 PUFA (fish oil source) in an experimental model of food allergy. Mice were sensitized (allergic group) or not (nonallergic group) with OVA and were fed with OVA diet to induce allergy signals. Mice were fed with regular diet in which 7% of lipid content was provided by soybean (5% of n-3 PUFA) or fish (25% of n-3 PUFA) oil. Allergic group mice had increased serum levels of antiovalbumin IgE and IgG1 and changes in small intestine, characterized by an increased edema, number of rolling leukocytes in microcirculation, eosinophil infiltration, mucus production, and Paneth cell degranulation, in comparison to non-allergic group. All these inflammatory parameters were reduced in mice fed high-n-3-PUFA diet. Our data together suggest that diet supplementation with n-3 PUFA from fish oil may consist of a valid adjuvant in food allergy treatment.

Estudo da eficácia da associação entre dexametasona, piroxican, cianocobalamina e orfenadrina (Rheumafim®) em modelos experimentais de inflamação em ratos / Efficacy of an association involving dexamethasone, piroxicam, cyanocobalamin and orphenadrine (Rheumafim®) in diverse inflammation models in rats

O cirurgião-dentista é diariamente apresentado a novos medicamentos, principalmente aqueles que objetivam a redução dos principais sinais clínicos pós-operatórios: dor e edema. Embora existam várias apresentações envolvendo drogas analgésicas e antiinflamatórias, em alguns casos se faz necessária a associação entre medicamentos, buscando uma eficácia ou uma duração de efeito maior. Recentemente, uma nova associação foi incluida no mercado farmacêutico visando a classe odontológica. O Rheumafim® é uma associação entre um antiinflamatório esteróide (dexamatasona), um não esteróide (piroxicam), uma vitamina com propriedades neuro-moduladoras (cianocobalamina), e, por fim, um relaxante muscular (orfenadrina). Neste trabalho, foi avaliada, em um modelo experimental, a eficácia da associação farmacológica entre os compostos do Rheumafim®, comparada individualmente com os antiinflamatórios presentes na formulação. Nossos dados demonstraram que o efeito analgésico alcançado com o tratamento dos animais com Rheumafim® foi superior aqueles obtido com o piroxicam e a dexametasona separadamente, em doses equivalentes. Entretanto, o efeito inibitório sobre a migração de leucócitos, bem como o antiedematogênio, foi observado de maneira similar no grupo tratado com a dexametasona e com o Rheumafim®. Nossos dados nos permitem concluir que a associação entre os princípios ativos do Rheumafim® promove uma potencialização do efeito analgésico e antiinflamatório final.

Dentists arefrequently presented to new drugs, manly to those that aim to control postoperative symptoms: pain and edema. In despite of the different available drugs, in some cases is necessary to combine two or more different drgs in order to achieve better therapeutic results. Recently, a new association involving four drugs was releases in the odontology market. Rheumaphim® is a pharmacological association involving a sterioidal anti-inflammatory drug (dexamathasone), a nonsteroidal anti-inflammatory drugs, vitamin B12, and a myorelaxant. In this work, we set up to evaluated experimentally, using animal model of inflammation, the efficacy of this drug in compassion to the anti-inflammatory drugs presented in this drug alone. Our data suggest that the analgesic effect achieved with Rhuemaphim® was higher in comparison with both anti-inflammatory drugs alone. However, edema and leokocyte migration inhibition were completely dependent on dexamethasone activity. Our data allow us to suggest that the drug association found in Rheumaphim® can promote better results in compariosn to each anti-inflammatory alone, considering the final anti-inflammatory effect.