Abstract The chemical hydroxymethylation of the antimicrobial nitrofurazone leads to the prodrug NFOH, also increases the anti-T. cruzi activities (in vitro and in vivo), as well as showed non-genotoxic (Ames and micronucleus assays). In the present study, we assessed the anti-T. cruzi effect of the NFOH In vivo - in acute Swiss and C57Bl/6 experimental Chagas models. The treatment started at 5 days post-infection during 20 consecutive days (orally, once day, 150mg/kg), and the parasitaemia as well as histopathology analysis were performed. In both experimental murine models, NFOH was able to reduce parasitemia blood avoiding parasitic reactivation, during immunosuppression period (dexamethasone 5mg/kg, 14 days), in 100% of the mice, and decrease tissue parasite nests, demonstrating absence of amastigote forms in all organs (100%) analyzed, data similar to benznidazole (BZN). Therefore, the results shown here pointing to the NFOH as promising compound for further preclinical studies, being a high potential drug to effective and safe chemotherapy to Chagas disease.

Resumo Introdução Dentre os efeitos terapêuticos da ozonioterapia, destacam-se a melhora do metabolismo celular e da oxigenação dos tecidos periféricos. Objetivo avaliar o efeito sistêmico da terapia bio-oxidativa com gás ozônio na cicatrização de feridas. Material e método Lesões teciduais com circunferência de 1,0 cm foram induzidas na pele do dorso de 24 ratos Wistar machos. Os animais foram divididos aleatoriamente em dois grupos: 1) Grupo C (controle; n = 12): com simulação da aplicação de gás ozônio pelo reto e, 2) Grupo O3 (teste; n = 12): com aplicação de gás ozônio por meio de insuflação retal na concentração de 50 µg / mL. Os animais foram sacrificados com sete e 15 dias, e as amostras foram retiradas, fixadas em formalina e submetidas às análises macroscópica, histológica e histométrica. Resultado Os animais do grupo O3 apresentaram inflamação mista aos sete dias, que se traduziu em ausência de inflamação aos 15 dias. O grupo C apresentou inflamação aguda no 7º dia, traduzindo-se em inflamação crônica, que aumentou significativamente do 7º para o 15º dia. Os achados mostraram que o grupo O3 apresentou maior contração da ferida (P <0,05) e maior grau de neovascularização no 7º dia (P <0,05) quando comparado ao grupo C. No 15º dia, ambos os grupos (O3 e C) apresentaram completa reepitelização, entretanto, o grupo O3 demonstrou completa regeneração muscular. Conclusão A ozonioterapia sistêmica teve efeito biomodulador, reduzindo as características de inflamação aguda e aumentando a reparação e regeneração tecidual na pele de ratos.

Abstract Introduction Among the therapeutic effects of ozone therapy, improvement in cell metabolism and peripheral tissue oxygenation have been highlighted. Objective to evaluate the systemic effect of bio-oxidative therapy with ozone gas on wound healing. Material and method Tissue lesions with a circumference of 1.0 cm were induced in the skin on the back of 24 male Wistar rats. The animals were randomly divided into two groups: 1) Group C (control; n=12): with simulation of the application of ozone gas via the rectum and, 2) Group O3 (test; n=12): with application of ozone gas by means of rectal insufflation at a concentration of 50 µg/mL. The animals were euthanized at seven and 15 days, and samples were removed, fixed in formalin, and submitted to macroscopic, histological, and histometric analyses. Result The animals in the O3 group presented mixed inflammation at seven days, which translated into an absence of inflammation at 15 days. The C group exhibited acute inflammation on the 7th day, translating to chronic inflammation, which significantly increased from the 7th to the 15th day. The findings showed that the O3 group presented greater wound contraction (P<0.05) and a greater degree of neovascularization on the 7th day (P<0.05) when compared to group C. On the 15th day, both groups (O3 and C) showed complete re-epithelialization, however, the O3 group demonstrated complete muscle regeneration. Conclusion The systemic ozone therapy had a biomodulatory effect, reducing the characteristics of acute inflammation and increasing tissue repair and regeneration in rat skin.

Abstract The main objective of this study was to cause bisphosphonate-related osteonecrosis of the jaws to develop in a rodent model. Adult male Holtzman rats were assigned to one of two experimental groups to receive alendronate (AL; 1 mg/kg/week; n = 6) or saline solution (CTL; n = 6). After 60 days of drug therapy, all animals were subjected to first lower molar extraction, and 28 days later, animals were euthanized. All rats treated with alendronate developed osteonecrosis, presenting as ulcers and necrotic bone, associated with a significant infection process, especially at the inter-alveolar septum area and crestal regions. The degree of vascularization, the levels of C-telopeptide cross-linked collagen type I and bone-specific alkaline phosphatase, as well as the bone volume were significantly reduced in these animals. Furthermore, on radiographic analysis, animals treated with alendronate presented evident sclerosis of the lamina dura of the lower first molar alveolar socket associated with decreased radiographic density in this area. These findings indicate that the protocol developed in the present study opens new perspectives and could be a good starting model for future property design.

O desenvolvimento do germe dental está associado a alterações morfológicas e bioquímicas da papila dental e do órgão do esmalte. A expressão e atividade de enzimas com atividade gelatinolítica de germes dentais dos primeiros molares de ratos recém nascidos e com 1, 3, 5, 7 10 e 15 dias de vida foram analisadas pelo método semiquantitativo da transcriptase reversa-reação da polimerase em cadeia (RT-PCR) e por enzimografia. Três enzimas com atividade gelatinolítica foram detectadas em todos os períodos e caracterizadas como sendo as formas latente e ativa da metaloproteinase de matriz-2 (MMP-2), utilizando-se como critérios à massa molecular e a atividade dependente dos íons Zn++ e Ca++. A expressão e atividade de MMP-2 aumentaram progressivamente do nascimento até o 15º dia de vida. A separação mecânica do germe dental demonstrou que a expressão de MMP-2 é maior na região da papila dental quando comparada ao órgão dental. Estes resultados indicam que a expressão e atividade de MMP-2 se apresentam variáveis durante o desenvolvimento e maturação do germe dental do primeiro molar de ratos.

Tooth germ development is associated with morphological and biochemical changes of the dental papilla and enamel organ. Enzymes with gelatinolytic activities were studied by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzymography in tooth germ of newborn to 15-day-old rats. Three major bands with gelatinolytic activity were detected at all periods and characterized as the latent and active forms of MMP-2 using their molecular weight and activity dependent on Zn++ and Ca++ ions as criteria. Expression and activity of MMP-2 increased progressively from 0 to 15 days after birth. Mechanical separation of the tooth germ from 10-day-old rats showed that the gelatinolytic activity was localized mainly in the dental papilla and not the dental organ. These data indicate that the expression and activity of MMP-2 varies during the development and maturation of rat first molar tooth germ.