Oral or topical administration of L-arginine changes the expression of TGF and iNOS and results in early wounds healing

ABSTRACT PURPOSE: To evaluate the contribution of L-arginine oral or topical rout of administration in the surgical wound healing process. METHODS: L-arginine was orally or topically administrated to mice after a laparotomy model procedure. The wounds were analyzed to evaluate the granulation tissue by HE analysis, collagen deposition, iNOS and cytokines production by immunochemisyry on wound progress. Mice used in this model were healthy, immunosupressed or diabetic and all of them were treated with different concentration of L-arginine and rout of administration. RESULTS: Suggested that groups treated with L-arginine orally or topically improved wound repair when compared with non-treatad mice. L- arginine treatment stimulated TGF-β and restricted NO production leading to a mild Th1 response and collagen deposition in injured area, when it was orally administrated. Topical administration decreased IL-8 and CCR1 expression by wound cells but did not interfere with TNF-α and IL-10 production, ratifying the decrease of inflammatory response, the oral administration however, presented a higher iNOS and TGF-β expression then. L-arginine treatment also improved the improved the wound healing in immunosupressed or diabetic mice. CONCLUSION: L-arginine administrated orally or topically can be considered an important factor in the recuperation of tissues.

Effects of metoclopramide on the expression of metalloproteinases and interleukins in left colonic anastomoses. An experimental study

PURPOSE : To evaluate the effects of metoclopramide on metalloproteinases (MMP) and interleukins (IL) gene expression in colonic anastomoses in rats. METHODS : Eighty rats were divided into two groups for euthanasia on the 3rd or 7th postoperative day (POD), then into two subgroups for sepsis induction or not, and then into subgroups to receive either metoclopramide or saline solution. Left colonic anastomosis were performed and then analyzed. RESULTS : On the 3rd POD, metoclopramide was associated with increased expression of MMP-1a, MMP-13, and TNF-α. On the 7th POD, the transcripts of all MMPs, TNF-α, IL-1β, IFN-γ, and IL-10 of the treated animals became negatively modulated. In the presence of sepsis, metoclopramide did not change MMPs and decreased IL-6, IL-1β, IFN-γ and IL-10 gene expression on the 3rd POD. On the 7th POD, increased expression of all MMPs, IFN-γ and IL-10 and negative modulated TNF-α and IL-6 gene expression. CONCLUSION : Administration of metoclopramide increased metalloproteinases and interleukins gene expression on the 3rd postoperative day and negatively modulated them on the 7th POD. In the presence of abdominal sepsis, metoclopramide did not change MMPs and decreased ILs gene expression on the 3rd POD. On the 7th POD, the drug increased expression of all MMPs.

Produção de interleucina-1beta e severidade da mastite pós-inoculação de Staphylococcus aureus na glândula mamária de bovinos e bubalinos / Interleukin - 1β production and severity of mastitis post-inoculation of Staphylococcus aureus in the mammary gland of bovines and bubalines

O presente trabalho objetivou avaliar, em vacas e em búfalas submetidas à mastite induzida por inoculação de Staphylococcus aureus, a concentração da citocina pró-inflamatória interleucina-1β (IL-1β), a contagem de células somáticas (CCS) e a correlação destas com alguns parâmetros da resposta local e sistêmica à inflamação. Os animais tiveram uma glândula mamária inoculada e o processo inflamatório foi monitorado pela cultura bacteriológica do leite, CCS, quantificação da IL-1β na secreção láctea, avaliação da aparência/consistência da glândula, aparência da secreção láctea (resposta localizada à inflamação) e aferição da temperatura retal (resposta sistêmica à inflamação). Houve elevação nos níveis de IL-1β, na CCS e resposta localizada e sistêmica à inflamação, tanto na espécie bovina como na bubalina. A cinética da produção da citocina foi diferente nas duas espécies (P<0,05), sendo que as búfalas apresentaram elevação mais rápida, porém com níveis menos elevados, quando comparadas às vacas. As duas espécies alcançaram contagens máximas semelhantes (P>0,05) de CS/mL de leite, com concentrações diferentes (P<0,05) de IL-1β/mL de leite. Os parâmetros utilizados para verificar a resposta localizada à inflamação demonstraram escores médios mais elevados na espécie bovina. Correlação positiva entre a concentração da IL-1β no leite, CCS e parâmetros utilizados para avaliar a severidade da mastite foi verificada somente na espécie bovina. Os resultados evidenciaram que a cinética de produção ...

This study aimed to analyze in cows and buffaloes, submitted to mastitis induced by inoculation of S. aureus, the concentration of the pro-inflammatory cytokine interleukin-1beta (IL-1β), the somatic cell count (SCC), and their correlation with some parameters of local and systemic response to inflammation. The animals had one mammary gland inoculated and the inflammatory process was monitored by milk culture, SCC, IL-1β measurement in the milk, evaluation of the gland appearance/consistency, milk secretion appearance (localized response to inflammation) and rectal temperature measurement (systemic response to inflammation). There was increase in the levels of IL-1β, SCC, and both local and systemic inflammatory response, in bovine and bubaline species. The production kinetics of the cytokine was different between the two species (P<0.05). Buffaloes showed a faster increase but achieved lower levels of interleukin-1beta, when compared to cows. Both species reached similar maximum counts (P>0.05) of SC/milk mL, with different concentrations (P<0.05) of IL-1β/mL. The parameters used to verify the local response to inflammation showed higher mean scores in bovine specie. Positive correlation between IL-1β concentration in the milk, SCC and parameters used to analyze the severity of mastitis was verified only in the bovine specie. The results evidenced that the kinetics of IL-1β production was different in the bovine and bubaline species, and demonstrated that the buffaloes developed a milder inflammatory process with faster recovery of the parameters used for mastitis severity evaluation.

Analysis of the tensile strength on the healing of the abdominal wall of rats treated with infliximab / Análise da força tênsil na cicatrização da parede abdominal de ratos tratados com infliximabe

PURPOSE: To evaluate the effects of infliximab, a murine/human chimeric monoclonal antibody, on the tensile strength of abdominal wall surgical wounds. METHODS: Sixty Wistar healthy male rats with initial body weight between 215 and 390 g and 60 and 90 days of age were randomly assigned into two groups, E (Experimental) and C (Control) with 30 animals each. Group E animals received a single subcutaneous dose of 5mg/Kg of infliximab, and Group C animals received equivalent subcutaneous volume of a solution of 0.9 percent NaCl. After 48h, animals from both groups were submitted to a 4 cm median incision in the abdominal wall, including all layers that had been reconstituted with continuous suture of the aponeurotic muscle and skin, with 5.0 nylon thread. Then, Group E animals were separated by simple allotment into three subgroups named E3, E7 and E14 with ten animals each, and those from group C into C3, C7, C14 and were submitted, respectively, the reoperation and euthanasia at the third, seventh and fourteenth postoperative day. The anterior abdominal wall, which was resected during reoperation, was cut with No 15 scalpel lamina perpendicularly to the surgical wound. Each specimen, in the form of a 6 cm x 2 cm strip, was fixed by the extremity so that the suture line was equidistant from the fixation points of the dynamometer, in order to undergo the tensile strength test. The dynamometer, which was gauged for each series of measures, was calibrated to apply velocity to the 25 mm/min rupture test; the rupture value was expressed in N (Newton). Prior to euthanasia, the abdominal vena cava was identified and punctured in order to collect blood for TNF-α dosage. RESULTS: The mean tensile strength found for animals from subgroups E3, E7, E14, C3, C7, C14 were, respectively, 16.03, 18.69, 27.01, 28.40, 27.22, 29.15 and 24.30 N. In the results of the multiple comparisons tests, significant differences (p<0.05) was found between subgroups...

OBJETIVO: Avaliar os efeitos do infliximabe, anticorpo monoclonal quimérico humano-murino, sobre a força tênsil da ferida operatória abdominal. MÉTODOS: Sessenta ratos, linhagem Wistar, machos, sadios, com peso corporal inicial entre 215 e 390 g e 60 e 90 dias de vida foram distribuídos aleatoriamente em dois grupos, E (Experimental) e C (Controle) com 30 animais cada. Os animais do grupo E receberam por via subcutânea, dose única, de 5mg/Kg de infliximabe, via subcutânea e os animais do grupo C receberam, volume equivalente, de solução de NaCl a 0,9 por cento, via subcutânea. Depois de 48h os animais de ambos os grupos foram submetidos à incisão mediana na parede abdominal com 4 cm de extensão incluindo todos os planos que foram reconstituídos com sutura contínua músculo aponeurótica e pele, separadamente, com fio de nylon 5.0. A seguir os animais grupo E foram separados por sorteio simples em três subgrupos denominados E3, E7 e E14 com dez animais e os do grupo C em C3, C7 e C14 e foram submetidos, respectivamente, à reoperação e eutanásia no terceiro, sétimo e 14º dia pós-operatório. A parede abdominal anterior, ressecada dos animais durante a reoperação, foi cortada, com lamina de bisturi nº 15, perpendicularmente à ferida operatória. Cada espécime, em forma de fita, com 6 cm por 2 cm, foi preso pela extremidade de modo que a linha de sutura ficasse eqüidistante dos pontos de fixação do dinamômetro e realizado o teste de resistência tensil. O dinamômetro, aferido a cada série de medidas, foi calibrado para aplicar velocidade do teste de ruptura de 25 mm/min e o valor de ruptura foi expresso em N (Newtons) Antes da eutanásia a veia cava abdominal foi identificada e puncionada para retirada de sangue para dosagem de TNF-α. RESULTADOS: A média da força tensil encontrada para os animais dos subgrupos E3, E7, E14, C3, C7 e C14 foram, respectivamente, 16,03; 18,69; 27,01; 28,40; 27,22; 29,15 e 24,30 N. Nos resultados dos testes de...

The pattern of immune cell infiltration in chromoblastomycosis: involvement of macrophage inflammatory protein-1 alpha/CCL3 and fungi persistence

Chromoblastomycosis (CR) is a subcutaneous chronic mycosis characterized by a granulomatous inflammatory response. However, little is known regarding the pattern of leukocyte subsets in CR and the pathways involved in their recruitment. The objective of this study was to assess the cellular subsets, chemokine, chemokine receptors and enzymes in CR. The inflammatory infiltrate was characterized by immunohistochemistry using antibodies against macrophages (CD68), Langerhans'cells (S100), lymphocytes (CD3, CD4, CD8, CD45RO, CD20 and CD56) and neutrophils (CD15). The expression of MIP-1alpha (Macrophage inflammatory protein-1alpha), chemokine receptors (CXCR3 and CCR1) and enzymes (superoxide dismutase-SOD and nitric oxide synthase-iNOS) was also evaluated by the same method. We observed an increase in all populations evaluated when compared with the controls. Numbers of CD15+ and CD56+ were significantly lower than CD3+, CD4+, CD20+ and CD68+ cells. Statistical analysis revealed an association of fungi numbers with CD3, CD45RO and iNOS-positive cells. Furthermore, MIP-1alpha expression was associated with CD45RO, CD68, iNOS and CXCR3. Our results suggest a possible role of MIP-1alpha and fungi persistence in the cell infiltration in CR sites.

A cromomicose é micose subcutânea crônica sistêmica caracterizada por resposta inflamatória crônica granulomatosa. No entanto, existem poucos dados a respeito do padrão de subtipos de leucócitos na cromomicose e sobre as vias envolvidas no recrutamento destas células. O objetivo deste trabalho foi avaliar os tipos celulares, bem como a expressão de quimiocinas, receptores de quimiocinas e enzimas em lesões de cromomicose. O infiltrado inflamatório foi caracterizado por meio de técnica imuno-histoquímica utilizando os seguintes marcadores CD68 (macrófagos), S100 (células de Langerhans), CD3, CD4, CD8, CD45RO, CD20 e CD56 (linfócitos) e CD15 (neutrófilos). A expressão de MIP-1alfa (Proteína Inflamatória do Macrófago-1alfa), receptores de quimiocinas (CXCR3 e CCR1) e enzimas (superóxido dismutase-SOD e óxido nítrico sintase induzida-iNOS) foi avaliada pelo mesmo método. Observou-se um aumento de todas as populações celulares avaliadas em relação às amostras controle. As populações de células CD15+ e CD56+ foram significativamente menores que células CD3+, CD4+, CD20+ e CD68+. A análise estatística revelou uma correlação positiva entre o número de fungos com as células CD3, CD45RO e iNOS-positivas. A expressão de MIP-1alfa foi também associada às populações de células CD45RO, CD68, iNOS e CXCR3 positivas. Nossos resultados apontam para um possível papel de MIP-1alfa e da persistência fúngica na infiltração de células inflamatórias nos sítios de cromomicose.