Protein kinase C zeta plays an essential role for Mycobacterium tuberculosis-induced extracellular signal-regulated kinase 1/2 activation in monocytes/macrophages via Toll-like receptor 2.

This study characterized the upstream signalling molecules involved in extracellular signal-regulated kinase (ERK) 1/2 activation and determined their effects on differential tumour necrosis factor (TNF)-alpha expression by monocytes/macrophages infected with virulent or avirulent mycobacteria. The avirulent Mycobacterium tuberculosis (MTB) strain H37Ra (MTBRa) induced higher levels of activation of ERK 1/2 and the upstream MAPK kinase (MEK)1 and, subsequently, higher levels of TNF-alpha expression in human primary monocytes and monocyte-derived macrophages, as compared with MTB strain H37Rv (MTBRv). The MTB-induced activation of ERK 1/2 was not dependent on Ras or Raf. However, inhibition of the activity of atypical protein kinase C (PKC) zeta decreased the in vitro phosphorylation of MEK, ERK 1/2 activation and subsequent TNF-alpha induction caused by MTBRv or MTBRa. Toll-like receptor (TLR) 2 was found to play a major role in MTB-induced TNF-alpha expression and PKCzeta phosphorylation. Co-immunoprecipitation experiments showed that PKCzeta interacts physically with TLR2 after MTB stimulation. Moreover, PKCzeta phosphorylation was increased more in macrophages following MTBRa, versus MTBRv, infection. This is the first demonstration that PKCzeta interacts with TLR2 to play an essential role in MTB-induced ERK 1/2 activation and subsequent TNF-alpha expression in monocytes/macrophages

ANÁLISE CLÍNICA E HISTOLÓGICA DA UTILIZAÇÃO DA RESINA ACRÍLICA AUTOPOLIMERIZÁVEL NAS FRATURAS DE MANDÍBULA E MAXILA E SEPARAÇÃO DA SÍNFISE MENTONIANA EM CÃES E GATOS CLINICAL AND HISTOLOGICAL EVALUATION OF ACRYLIC RESIN IN THE FRACTURE OF THE MANDIBLE AND MAXILLA AND SEPARATION OF MANDIBULAR SYMPHISIS IN DOGS AND CATS

O trabalho foi desenvolvido em duas fases. A primeira constou de aplicação de resina acrílica autopolimerizável sobre dentes de cães experimentais, sem condicionamento ácido do esmalte dental; a gengiva foi analisada histologicamente nos períodos de um, três, sete, 14, 21 e 30 dias. A segunda fase foi conduzida em 20 cães e 10 gatos com fraturas do sistema estomatognático, atendidos no Ambulatório Central da FMVZ/USP. Nessa segunda fase, clínica, foi aplicado condicionamento ácido do esmalte. A resina era usada nas fraturas rostrais às raízes distais do primeiro molar inferior e do quarto pré-molar superior, bem como na separação da sínfise mentoniana. Os resultados da primeira fase mostraram que mesmo sem o condicionamento ácido houve aderência da resina acrílica sobre os dentes, embora houvesse necessidade de maior volume do material, o que provocou ulcerações dos tecidos moles da boca. Essa fase também evidenciou, à sondagem, que o epitélio de aderência sulcular permaneceu aderido, além de gengivite, ulceração da gengiva, língua e mucosa alveolar. A análise histológica revelou predominantemente ulceração dos tecidos em contato com a resina. Na segunda fase, todos os animais evidenciaram consolidação óssea das fraturas, além de gengivite e ulceração. Lesões periodontais foram encontradas em dois animais dos quais a resina foi removida tardiamente, com quatro e 12 meses após a aplicação, respectivamente. Em ambas as fases, os animais adaptaram-se bem à resina sobre os dentes.<br>This paper was performed in two phases. In the first one, the stability of the acrylic resin over the teeth of dogs, without enamel acid conditioning, the clinical and histological reaction on the gingiva were analyzed in periods of 1, 3, 7, 14, 21 and 30 days. The second phase was conducted in 20 dogs and 10 cats, with acid etching technique. The resin was used in the rostral fractures to the distal roots of the lower first molar and upper fourth premolar, as well as in the separation of the symphisis. The results of the first phase indicated that even without the acid etching technique, the acrylic resin remained fixed over the teeth, although a higher volume of resin was needed, thus inducing more areas of ulceration on the lips, gingiva and tongue. This phase also demonstrated that the sulcular gingival adhesion epithelium remained attached to the teeth. Gingivitis, ulceration on the gingiva, tongue and alveolar mucosa were also observed. The histologic analyses mainly showed ulceration of the gingival epithelium. In the second phase all animals featured clinical bone healing in the site of fracture, as well as gingivitis and ulceration. Periodontitis was found in two animals whose resin was not removed up to four and twelve months after application of the acrylic resin. The results also showed that the method can be used in fractures rostral to the distal roots of upper fourth pre-molar an first lower molar