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Oral candidiasis (OC) is an infectious disease caused by microorganisms of the genus Candida, leading to lesions in the buccal cavity. Its treatment consists of the administration of topical or systemic antifungal agents, which may compromise the patient compliance due to its side effects, highlighting the need for alternative treatments. In this scenario, bullfrog oil, an animal oil composed of a pool of saturated and unsaturated fatty acids, is introduced as a potential antifungal raw material. Thus, the aim of this work was to produce a mucoadhesive emulsified system able to deliver the bullfrog oil in the buccal cavity to treat the OC. The emulsion was produced and characterized by visual inspection, droplet size, polydispersity index (PdI), and zeta potential over the course of 60 days. In addition, its mucoadhesive ability was evaluated using an in vitro mucin model. The antifungal activity, evaluated by the broth microdilution assay and the biocompatibility, performed against human erythrocytes, were also carried out. The emulsion showed a droplet size of 320.79 ± 35.60 nm, a PdI of 0.49 ± 0.08, and a zeta potential of -38.53 ± 6.23 mV, with no significant changes over 60 days. The mucoadhesive properties of the system was improved by the use of pharmaceutical excipients. The antifungal activity showed that the bullfrog oil and the emulsion were able to inhibit the growth of different Candida species. Furthermore, the emulsion showed no significant hemolytic effect. Overall, the system showed suitable physicochemical characteristics and biocompatibility, with substantial in vitro antifungal activity, suggesting that this system can be further investigated for OC treatment.

RESUMO

OBJECTIVE: simvastatin has pleiotropic anti-inflammatory and immunomodulatory effects potentially usefull to prevent chemotherapy-induced gastrointestinal mucositis. Studies on this are scarce. This study aimed to examine the effects of simvastatin on gastric and intestinal mucositis after 5-fluorouracil (5-FU) treatment in rats. METHODS: rats weighing 270±18g were divided into two groups. The 5-FU+saline group (5-FU/SAL) rats were treated with 5-FU (50mg/kg) plus 0.9% saline orally (gavage) once daily for five days. The 5-FU+simvastatin (5-FU/SIMV) group was treated with 5-FU (50mg/kg), plus simvastatin (10mg/kg), in the same way. The rats were euthanased on the sixth day, then their stomach and intestine were photographed and removed for exams. Dosages of serum TNF-a, IL-1ß, IL-6 and histopathology were done for stomach and intestine. RESULTS: body-weight was significantly lower in rats treated with 5-FU+saline than the weight loss of the 5-FU/SIMV group rats. TNF-a expression was lower in 5-FU/SIMV group (172.6±18pg/ml) than in 5-FU/SAL (347.5±63pg/ml). Serum IL-1b was lower in 5-FU/SAL group (134.5±23pg/ml) than in 5-FU/SIMV (48.3±9pg/ml). Serum IL-6 was 61.8±15pg/ml in 5-FU/SIMV and 129.4±17pg/ml in 5-FU/SAL groups. These differences were significant (p<0.05). Mucosal damage in stomach and jejunum were observed in rats receiving 5-FU alone. In the stomach and jejunum, simvastatin caused significant protective effects against 5-FU-induced mucosal injury. CONCLUSION: simvastatin attenuated gastric and intestinal mucositis related to 5-FU therapeutics in animal model. These data encourage forthcoming clinical studies addressing the usefulness of statins in the prevention and treatment of gastrointestinal mucositis.

OBJETIVO: examinar os efeitos da sinvastatina na mucosite gástrica e intestinal após o tratamento com 5-fluorouracil (5-FU), determinados pela expressão de citocinas e histologia em ratos. MÉTODOS: ratos pesando 270±15g foram divididos em dois grupos. O grupo 5-FU+salina foi tratado com 5-FU (50mg/kg) mais solução salina a 0,9% por gavagem uma vez ao dia por cinco dias. O grupo 5-FU+sinvastatina foi tratado com 5-FU (50mg/kg), mais sinvastatina (10mg/kg), da mesma forma. Foi feita a eutanásia dos animais no sexto dia. O estômago e o intestino foram fotografados e removidos para exame. Dosagens séricas de TNF-a, IL-1ß, IL-6 e histopatologia (coloração HE) do estômago e intestino foram realizadas. RESULTADOS: o peso corporal diminuiu em ratos no grupo 5-FU+salina. A sinvastatina não inibiu a perda de peso induzida pelo 5-FU. Danos significativos da mucosa no estômago e no jejuno foram observados em ratos que receberam apenas 5-FU. As dosagens séricas de citocinas foram significativamente menores no grupo 5-FU+sinvastatina do que no grupo 5-FU (p<0,05). A sinvastatina causou efeitos protetores significativos contra as lesões da mucosa gástrica e jejunal induzidas por 5-FU. CONCLUSÃO: a sinvastatina atenua a mucosite gástrica e intestinal relacionada à terapêutica com 5-FU. Nossos dados encorajam futuros estudos pré-clínicos e clínicos sobre a utilidade das estatinas na prevenção da mucosite gastrointestinal.

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RESUMO Objetivo: examinar os efeitos da sinvastatina na mucosite gástrica e intestinal após o tratamento com 5-fluorouracil (5-FU), determinados pela expressão de citocinas e histologia em ratos. Métodos: ratos pesando 270±15g foram divididos em dois grupos. O grupo 5-FU+salina foi tratado com 5-FU (50mg/kg) mais solução salina a 0,9% por gavagem uma vez ao dia por cinco dias. O grupo 5-FU+sinvastatina foi tratado com 5-FU (50mg/kg), mais sinvastatina (10mg/kg), da mesma forma. Foi feita a eutanásia dos animais no sexto dia. O estômago e o intestino foram fotografados e removidos para exame. Dosagens séricas de TNF-a, IL-1ß, IL-6 e histopatologia (coloração HE) do estômago e intestino foram realizadas. Resultados: o peso corporal diminuiu em ratos no grupo 5-FU+salina. A sinvastatina não inibiu a perda de peso induzida pelo 5-FU. Danos significativos da mucosa no estômago e no jejuno foram observados em ratos que receberam apenas 5-FU. As dosagens séricas de citocinas foram significativamente menores no grupo 5-FU+sinvastatina do que no grupo 5-FU (p<0,05). A sinvastatina causou efeitos protetores significativos contra as lesões da mucosa gástrica e jejunal induzidas por 5-FU. Conclusão: a sinvastatina atenua a mucosite gástrica e intestinal relacionada à terapêutica com 5-FU. Nossos dados encorajam futuros estudos pré-clínicos e clínicos sobre a utilidade das estatinas na prevenção da mucosite gastrointestinal.

ABSTRACT Objective: simvastatin has pleiotropic anti-inflammatory and immunomodulatory effects potentially usefull to prevent chemotherapy-induced gastrointestinal mucositis. Studies on this are scarce. This study aimed to examine the effects of simvastatin on gastric and intestinal mucositis after 5-fluorouracil (5-FU) treatment in rats. Methods: rats weighing 270±18g were divided into two groups. The 5-FU+saline group (5-FU/SAL) rats were treated with 5-FU (50mg/kg) plus 0.9% saline orally (gavage) once daily for five days. The 5-FU+simvastatin (5-FU/SIMV) group was treated with 5-FU (50mg/kg), plus simvastatin (10mg/kg), in the same way. The rats were euthanased on the sixth day, then their stomach and intestine were photographed and removed for exams. Dosages of serum TNF-a, IL-1ß, IL-6 and histopathology were done for stomach and intestine. Results: body-weight was significantly lower in rats treated with 5-FU+saline than the weight loss of the 5-FU/SIMV group rats. TNF-a expression was lower in 5-FU/SIMV group (172.6±18pg/ml) than in 5-FU/SAL (347.5±63pg/ml). Serum IL-1b was lower in 5-FU/SAL group (134.5±23pg/ml) than in 5-FU/SIMV (48.3±9pg/ml). Serum IL-6 was 61.8±15pg/ml in 5-FU/SIMV and 129.4±17pg/ml in 5-FU/SAL groups. These differences were significant (p<0.05). Mucosal damage in stomach and jejunum were observed in rats receiving 5-FU alone. In the stomach and jejunum, simvastatin caused significant protective effects against 5-FU-induced mucosal injury. Conclusion: simvastatin attenuated gastric and intestinal mucositis related to 5-FU therapeutics in animal model. These data encourage forthcoming clinical studies addressing the usefulness of statins in the prevention and treatment of gastrointestinal mucositis.

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OBJECTIVE: to evaluate whether colectomy, associated with 70% hepatectomy, influences liver regeneration in rats. METHODS: we distributed 18 Wistar rats in three groups of six animals each. In group I (sham), we performed laparotomy; In group II, colectomy + 70% hepatectomy; In group III, only 70% hepatectomy. On the 6th postoperative day, we collected blood by cardiac puncture under anesthesia, followed by euthanasia. We performed serum dosages of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin and alkaline phosphatase (AF), hepatocyte growth factor (HGF) and transforming growth factor-α (TGF-α). We calculated liver regeneration by the formula: liver weight ratio per 100g body weight at the time of euthanasia / liver weight preoperatively projected for 100g body weight × 100. RESULTS: ALT and AST levels were significantly lower in group II when compared with group III (p<0.001). Albuminemia showed significantly higher levels in group II. Levels of HGF and TGF-α in group II were significantly higher than in group III. The percentage of hepatic regeneration was significantly higher in group II than in group III. CONCLUSION: Colectomy performed simultaneously with 70% hepatectomy had a positive influence on liver regeneration in rats. Further research is needed to reveal the molecular mechanisms of this effect and to characterize the colon influence in liver physiology.

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ABSTRACT Objective: to evaluate whether colectomy, associated with 70% hepatectomy, influences liver regeneration in rats. Methods: we distributed 18 Wistar rats in three groups of six animals each. In group I (sham), we performed laparotomy; In group II, colectomy + 70% hepatectomy; In group III, only 70% hepatectomy. On the 6th postoperative day, we collected blood by cardiac puncture under anesthesia, followed by euthanasia. We performed serum dosages of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin and alkaline phosphatase (AF), hepatocyte growth factor (HGF) and transforming growth factor-α (TGF-α). We calculated liver regeneration by the formula: liver weight ratio per 100g body weight at the time of euthanasia / liver weight preoperatively projected for 100g body weight × 100. Results: ALT and AST levels were significantly lower in group II when compared with group III (p<0.001). Albuminemia showed significantly higher levels in group II. Levels of HGF and TGF-α in group II were significantly higher than in group III. The percentage of hepatic regeneration was significantly higher in group II than in group III. Conclusion: Colectomy performed simultaneously with 70% hepatectomy had a positive influence on liver regeneration in rats. Further research is needed to reveal the molecular mechanisms of this effect and to characterize the colon influence in liver physiology.

RESUMO Objetivo: avaliar se a colectomia, associada à hepatectomia 70%, influencia a regeneração do fígado em ratos. Métodos: foram utilizados 18 ratos Wistar distribuídos em três grupos de seis animais cada. No grupo I (sham) foi realizada laparotomia; no grupo II colectomia + hepatectomia 70%; no grupo III apenas hepatectomia 70%. No sexto dia pós-operatório foi colhido sangue por punção cardíaca, sob anestesia, seguido de eutanásia. Foram realizadas dosagens séricas de aspartato aminotransferase (AST), alanina aminotransferase (ALT), albumina e fosfatase alcalina (FA), fator de crescimento de hepatócitos (HGF) e fator de crescimento transformador-α (TGF-α). A regeneração do fígado foi calculada pela fórmula: razão peso do fígado por 100g do peso corporal no momento da eutanásia/peso do fígado no pré-operatório projetado por 100g de peso corporal ×100. Resultados: Os níveis de ALT e AST foram significativamente menores no grupo II quando comparados com o grupo III (p<0,001). A albuminemia mostrou níveis significativamente mais elevados no grupo II. Os níveis de HGF e TGF-α no grupo II foram significativamente mais elevados que no grupo III. O percentual de regeneração hepática foi significativamente mais elevado no grupo II do que no grupo III. Conclusão: o estudo demonstrou que a colectomia realizada simultaneamente à hepatectomia 70% influenciou positivamente na regeneração do fígado em ratos. Pesquisas adicionais são necessárias para revelar os mecanismos moleculares deste efeito e para caracterizar a influência do cólon na fisiologia do fígado.

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OBJECTIVE: To evaluate the effects of different times of ischemic preconditioning (IPC) on intestinal bacterial translocation (BT). METHODS: Thirty Wistar rats weighing 280 ± 27 g were divided into five groups. In the IR group (n = 6), laparotomy was performed and the superior mesenteric artery was occluded by an atraumatic microclamp for 30 minutes. In the four preconditioning groups (n = 6 each) before the 30 minutes of ischemia-reperfusion (I/R) rats underwent IPC for two, five, ten and 15 minutes, followed by the same time of reperfusion. In order to assess whether the time of preconditioning influenced the onset of bacterial translocation, samples of mesenteric lymph nodes, liver and spleen were collected in sterile conditions twenty-four hours after the procedures for quantification of bacterial colony forming units per gram of tissue (CFU/g). Blood was collected for measurement of cytokines. RESULTS: In the I/R group, the total CFU/g in mesenteric lymph nodes, spleen, liver, as well as the serum TNF-á, IL-1â and IL-6 were significantly higher than in the other groups (p <0.05). Preconditioning for 15 minutes significantly attenuated BT and serum cytokines when compared to other periods of preconditioning (p <0.05). CONCLUSION: Our data suggest preconditioning as a key factor to reduce bacterial translocation in intestinal I/R. On a scale of two to 15 minutes, the best time of ischemic preconditioning for the attenuation of bacterial translocation was 15 minutes.

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Oxidative stress is associated with postmenopause and is also responsible for various metabolic alterations. The redox imbalance observed during ovarian decline can be induced experimentally by bilateral ovariectomy in rats. In addition to hormone replacement, regular moderate physical exercise is indicated to prevent several common postmenopausal diseases. This study aimed to assess the effect of daily swimming on the antioxidant defense system of oophorectomized Wistar rats. Control and oophorectomized groups were submitted to 1 h of daily swimming for 90 days. Levels of lipid peroxidation and glutathione content and the activities of superoxide dismutase enzyme and glutathione peroxidase in erythrocytes, liver, and brain were assessed every 30 days. The control group exhibited lower lipoperoxidation that was associated with a significant increase in superoxide dismutase enzyme activity, glutathione peroxidase activity, and glutathione content in erythrocytes and liver; however, swimming did not cause changes in antioxidant parameters in the brain over time. The oophorectomized group showed no antioxidant adaptation to daily swimming and had greater oxidative damage in the liver and blood. Our results suggest that ovariectomy hinders antioxidant adaptation in Wistar rats submitted to daily swimming.

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OBJETIVO: avaliar os efeitos de diferentes tempos de pré-condicionamento isquêmico(PCI) intestinal sobre a translocação bacteriana (TB). MÉTODOS: Trinta ratos Wistar pesando 280±27g foram alocados em cinco grupos. No grupo IR (n=6), foi realizada laparotomia e a artéria mesentérica superior foi ocluída por microclampe atraumático por 30 minutos. Nos quatro grupos com pré-condicionamento (n=6 cada), antes dos 30 minutos de isquemia-reperfusão (I/R) os ratos foram submetidos a PCI de dois, cinco, dez e 15 minutos e, em seguida, ao mesmo tempo de reperfusão. Vinte e quatro horas após, para avaliar se os tempos de pré-condicionamento influenciam o aparecimento de translocação bacteriana, amostras de linfonodos mesentéricos, fígado e baço foram coletadas em condições estéreis, para quantificação de unidades formadoras de colônias bacterianas por grama de tecido (UFC/g). Sangue foi coletado para dosagem de citocinas. RESULTADOS: No grupo I/R, o total de UFC/g em linfonodos mesentéricos, baço, fígado, bem como, a dosagem sérica de TNF-a, IL-1b e IL-6 foram significativamente maiores do que nos demais grupos (p<0,05). Pré-condicionamento de 15 minutos atenuou significativamente a BT e as citocinas séricas, comparando com os outros tempos de pré-condicionamento (p<0,05). CONCLUSÃO: Nossos dados sugerem o pré-condicionamento como fator-chave para reduzir translocação bacteriana em I/R intestinal. Numa escala de dois a 15 minutos, o melhor tempo de pré-condicionamento isquêmico para a atenuação da translocação bacteriana foi 15 minutos.

OBJECTIVE: To evaluate the effects of different times of ischemic preconditioning (IPC) on intestinal bacterial translocation (BT). METHODS: Thirty Wistar rats weighing 280 ± 27g were divided into five groups. In the IR group (n = 6), laparotomy was performed and the superior mesenteric artery was occluded by an atraumatic microclamp for 30 minutes. In the four preconditioning groups (n = 6 each) before the 30 minutes of ischemia-reperfusion (I/R) rats underwent IPC for two, five, ten and 15 minutes, followed by the same time of reperfusion. In order to assess whether the time of preconditioning influenced the onset of bacterial translocation, samples of mesenteric lymph nodes, liver and spleen were collected in sterile conditions twenty-four hours after the procedures for quantification of bacterial colony forming units per gram of tissue (CFU/g). Blood was collected for measurement of cytokines. RESULTS: In the I/R group, the total CFU/g in mesenteric lymph nodes, spleen, liver, as well as the serum TNF-á, IL-1â and IL-6 were significantly higher than in the other groups (p <0.05). Preconditioning for 15 minutes significantly attenuated BT and serum cytokines when compared to other periods of preconditioning (p <0.05). CONCLUSION: Our data suggest preconditioning as a key factor to reduce bacterial translocation in intestinal I/R. On a scale of two to 15 minutes, the best time of ischemic preconditioning for the attenuation of bacterial translocation was 15 minutes.

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The aim of this work was to evaluate how an aqueous micellar system containing Amphotericin B (AmB) and sodium deoxycholate (DOC) can be rebuilt after heating treatment. Also, a review of the literature on the physicochemical and biological properties of this new system was conducted. Heated (AmB-DOC-H) and unheated (AmB-DOC) micelles were then diluted at four different concentrations (50 mg · L(-1), 5 mg · L(-1), 0.5 mg · L(-1), and 0.05 mg · L(-1)) to perform physicochemical studies and a pharmacotoxicity assay, in which two cell models were used for the in vitro experiments: red blood cells (RBC) from human donors and Candida parapsilosis (Cp). While potassium (K(+)) and hemoglobin leakage from RBC were the parameters used to evaluate acute and chronic toxicity, respectively, the efficacy of AmB-DOC and AmB-DOC-H were assessed by K(+) leakage and cell survival rate from Cp. The spectral study revealed a slight change in the AmB-DOC aggregate peak from 327 nm to 323 nm, which is the peak for AmB-DOC-H. Although AmB-DOC and AmB-DOC-H exhibited different behavior for hemoglobin leakage, AmB-DOC produced higher leakage than AmB-DOC-H at high concentrations (from 5 mg · L(-1)). For K(+) leakage, both AmB-DOC and AmB-DOC-H showed a similar profile for both cell models, RBC and Cp (P < 0.05). AmB-DOC-H and AmB-DOC also revealed a similar profile of activity against Cp with an equivalent survival rate. In short, AmB-DOC-H showed much less toxicity than AmB-DOC, but remained as active as AmB-DOC against fungal cells. The results highlight the importance of this new procedure as a simple, inexpensive, and safe way to produce a new kind of micelle system for the treatment of systemic fungal infections.

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O objetivo deste estudo foi avaliar a atividade antibacteriana in vitro e cicatrizante do óleo de buriti (M. flexuosa) em feridas realizadas em ratos (Rattus norvegicus albinus). Para a avaliação antibacteriana in vitro, foram utilizados cinco patógenos bacterianos incluindo espécies gram-positivas e espécies gram-negativas mediante o uso do método de difusão em ágar. Para a avaliação da atividade cicatrizante, foram utilizados 40 ratos da linhagem Wistar, divididos em dois grupos: o grupo I, composto por 20 ratos com feridas cutâneas, tratados com aplicação tópica do creme base com 10 por cento de óleo de buriti, e o grupo II, controle, com o mesmo número de animais que receberam a aplicação tópica do creme base. A aplicação do produto foi realizada em feridas padronizadas, circulares de 1cm de diâmetro na região dorsolombar. As avaliações clínica, morfométrica e histopatológica das feridas foram realizadas no 3°, 7°, 14° e 21° dias. Em relação à avaliação da atividade antibacteriana, os resultados mostraram que houve inibição do crescimento bacteriano em quatro dos cinco patógenos testados. Em relação à área da ferida, foi observada redução significativa da área no 14o dia e maior percentual de contração das feridas do grupo tratado em relação ao controle. No décimo quarto dia, as feridas tratadas com o óleo do buriti apresentavam aumento significativo na contagem de fibroblastos e fibras colágenas, além de completo processo de reepitelização, enquanto o grupo controle necessitava de mais tempo para resolução do processo cicatricial.

The aim of this study was to evaluate the in vitro antimicrobial activity and wound healing effect of buriti oil (M. flexuosa) in rats. To evaluate the in vitro antimicrobial activity, five species of bacteria, including both gram-negative and gram-positive, were tested by the agar diffusion method. To assess the wound healing effect, 40 rats of Wistar lineage were clustered into two groups: G1, composed by 20 rats with cutaneous wounds and treated using topic administration of basic cream containing 10 percent of buriti oil; and G2 or control group, composed by 20 rats with cutaneous wounds and treated using topic administration of basic cream without any buriti oil. The cream administration was performed on circular wounds of 1 cm area in the lumbodorsal region. Clinical, histopathologic and morphometric evaluations of the wounds were done in 3rd, 7th, 14th and 21th days. Four from five bacteria species tested had growing inhibition, which demonstrates the antimicrobial potential of buriti oil. A significant reduction on the wound area with contraction of the edges was found for G1 in the 14th day. On this same day, the wounds treated using buriti oil showed an increase in the fibroblasts and collagen fibers countings and complete reephitelialization, characteristics not demonstrated by G2.