RESUMEN
Pre-clinical assays demonstrated that a 1% polyvinyl alcohol biomembrane containing latex proteins (10%) from the medicinal plant Calotropis procera was biocompatible and stimulated healing of incisional and excisional wounds in murine models, and the mechanistic aspects were established. The efficacy of the biomembrane (BioMemCpLP) to promote healing of chronic ulcers in leprosy patients was investigated. The study started with 28 volunteers. Five were excluded later due to different disconformities. Ulcers from 15 patients were continuously treated with BioMemCpLP for 56 days. Five patients were treated only with silver sulfadiazine and three patients received plain hydrocolloid wound dressings with high absorption capacity. In all cases, wound dressings were renewed three times a week for 56 days and ulcers were evaluated weekly for contraction and healing progress. The extent of the healed area in the ulcers treated with BioMemCpLP was greater than in the control groups. Approximately 88% of ulcers treated with BioMemCpLP were fully healed before day 56, against 6% in both control groups. This result was not correlated with age/gender, duration or location of ulcers, deformity or whether or not the patient was cured of leprosy. The results showed that BioMemCpLP was beneficial for treatment of ulcers suffered by leprosy patients without noticeable side effects.
Asunto(s)
Calotropis , Látex , Lepra , Cicatrización de Heridas , Calotropis/química , Femenino , Masculino , Cicatrización de Heridas/efectos de los fármacos , Humanos , Látex/química , Persona de Mediana Edad , Adulto , Lepra/complicaciones , Lepra/tratamiento farmacológico , Proteínas de Plantas/administración & dosificación , Proteínas de Plantas/farmacología , Enfermedad Crónica , Úlcera del Pie/tratamiento farmacológico , Úlcera del Pie/etiología , Anciano , Resultado del Tratamiento , Adulto JovenRESUMEN
Clinical oncology has shown outstanding progress improving patient survival due to the incorporation of new drugs. However, treatment success may be reduced by the emergency of dose-limiting side effects, such as intestinal mucositis and diarrhea. Mucositis and diarrhea management is symptomatic, and there is no preventive therapy. Bacterial and fungal-based compounds have been suggested as an alternative for preventing the development of diarrhea in cancer patients. Using probiotics is safe and effective in immunocompetent individuals, but concerns remain during immunosuppressive conditions. Paraprobiotics, formulations composed of non-viable microorganisms, have been proposed to overcome such limitation. The present literature review discusses current evidence regarding the possible use of paraprobiotics as an alternative to probiotics to prevent gastrointestinal toxicity of cancer chemotherapy.
Asunto(s)
Antineoplásicos , Mucositis , Neoplasias , Probióticos , Humanos , Antineoplásicos/efectos adversos , Diarrea/inducido químicamente , Diarrea/prevención & control , Mucositis/inducido químicamente , Mucositis/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Probióticos/uso terapéutico , Probióticos/farmacologíaRESUMEN
Clinical oncology has shown outstanding progress improving patient survival due to the incorporation of new drugs. However, treatment success may be reduced by the emergency of dose-limiting side effects, such as intestinal mucositis and diarrhea. Mucositis and diarrhea management is symptomatic, and there is no preventive therapy. Bacterial and fungal-based compounds have been suggested as an alternative for preventing the development of diarrhea in cancer patients. Using probiotics is safe and effective in immunocompetent individuals, but concerns remain during immunosuppressive conditions. Paraprobiotics, formulations composed of non-viable microorganisms, have been proposed to overcome such limitation. The present literature review discusses current evidence regarding the possible use of paraprobiotics as an alternative to probiotics to prevent gastrointestinal toxicity of cancer chemotherapy.
RESUMEN
It was previously demonstrated that the methanol fraction of Sideroxylon obtusifolium (MFSOL) promoted anti-inflammatory and healing activity in excisional wounds. Thus, the present work investigated the healing effects of MFSOL on human keratinocyte cells (HaCaT) and experimental burn model injuries. HaCaT cells were used to study MFSOL's effect on cell migration and proliferation rates. Female Swiss mice were subjected to a second-degree superficial burn protocol and divided into four treatment groups: Vehicle, 1.0% silver sulfadiazine, and 0.5 or 1.0% MFSOL Cream (CrMFSOL). Samples were collected to quantify the inflammatory mediators, and histological analyses were performed after 3, 7, and 14 days. The results showed that MFSOL (50 µg/mL) stimulated HaCaT cells by increasing proliferation and migration rates. Moreover, 0.5% CrMFSOL attenuated myeloperoxidase (MPO) activity and also stimulated the release of interleukin (IL)-1ß and IL-10 after 3 days of treatment. CrMFSOL (0.5%) also enhanced wound contraction, promoted improvement of tissue remodeling, and increased collagen production after 7 days and VEGF release after 14 days. Therefore, MFSOL stimulated human keratinocyte (HaCaT) cells and improved wound healing via modulation of inflammatory mediators of burn injuries.
Asunto(s)
Quemaduras , Sapotaceae , Quemaduras/tratamiento farmacológico , Femenino , Humanos , Queratinocitos , Metanol , Hojas de la Planta , Prolina , Cicatrización de HeridasRESUMEN
The high prevalence of exercise-induced pulmonary hemorrhage (EIPH) in athletic horses constitutes to be a challenge to the racing industry and a source of major concern to animal welfare. Both experimental and clinical evidence indicate that the use of autologous platelet-rich plasma (PRP) is a promising effector of repair in a variety of pulmonary conditions. The present study evaluated the effect of intrabronchial instillation of PRP on EIPH endoscopic scores from 37 Thoroughbred racehorses. Inclusion criteria were for animals to be EIPH-positive in, at least, two consecutive post-exercise endoscopic exams and to receive 250mg of furosemide IV four hours before racing. Animals were randomly assigned into 3 groups: placebo, control, and PRP instillation. All 37 Thoroughbred racehorses included had EIPH endoscopic scores pre- and post- treatment compared by statistical analysis. The bleeding score from the group receiving PRP was significantly lower than in the control and placebo groups. No adverse effects were observed in any animal during or after the experiment. It was possible to conclude that the intrabronchial instillation of autologous PRP was effective in reducing EIPH scores in racehorses receiving furosemide and that this bioproduct can be considered as a promising coadjuvant in controlling EIPH in athletic horses.(AU)
A alta prevalência de hemorragia pulmonar induzida por exercício (HPIE) em cavalos atletas é um desafio de longa data para a indústria de corridas, além de figurar como grande preocupação sobre o bem-estar animal. As evidências experimentais e clínicas indicam que o uso do plasma rico em plaquetas (PRP) de fonte autógena é promissor na terapêutica de diversas lesões pulmonares. O presente estudo objetivou avaliar as mudanças após corrida no escore endoscópico de HPIE de 37 cavalos Puro-Sangue Inglês que receberam instilação intrabronquial de PRP autólogo. Os animais selecionados eram HPIE-positivos em, ao menos, dois exames endoscópicos consecutivos e recebiam 250mg de furosemida IV administrado quatro horas antes de cada corrida. Na comparação dos escores endoscópicos pré e pós-tratamento, verificou-se que o escore de HPIE do grupo tratado com PRP foi significantemente menor que o dos grupos controle e placebo. Nenhum efeito adverso foi observado nos animais durante ou após o experimento. Concluiu-se que a instilação intrabronquial de PRP autólogo foi efetiva na redução do escore de HPIE de cavalos de corrida usuários de furosemida e que este bioproduto pode ser considerado uma alternativa promissora no controle de HPIE em cavalos atletas.(AU)
Asunto(s)
Animales , Condicionamiento Físico Animal/efectos adversos , Plasma Rico en Plaquetas , Lesión Pulmonar Aguda/veterinaria , Caballos/fisiología , Instilación de Medicamentos , Furosemida/análisis , Hemorragia/veterinariaRESUMEN
Amylin is a pancreatic hormone cosecreted along with insulin and involved in pancreatic amyloidosis and ß-cell apoptosis in diabetic cats and humans. Amylin is usually elevated in early stages of type 2 diabetes but recently was found to be increased in acute and chronic pancreatitis in humans. Currently, there are little data about feline amylin propensity to fibrillate and no information on circulating levels of this hormone during feline pancreatitis. We compared 4 amylin analogues and found cat amylin to be more prone to amyloid fibrillation than human amylin, the triple-proline analogue pramlintide and rat amylin. We also measured plasma amylin levels in healthy lean cats, diabetic cats, and cats with pancreatitis. Plasma amylin was higher in diabetic cats compared with healthy lean cats (P < 0.001). Interestingly, amylin levels during pancreatitis were higher than those of both lean cats (P < 0.0001) and diabetic cats without pancreatitis (P < 0.005). These data support evidence of feline amylin being more prone to aggregation than human amylin in vitro, which may influence diabetes mellitus progression and ß-cell failure in vivo. Furthermore, our data show an increase in amylin levels during feline pancreatitis and the need for future research on the role of this hormone in the pathogenesis of pancreatic inflammation associated to feline diabetes mellitus.
Asunto(s)
Enfermedades de los Gatos/patología , Diabetes Mellitus/veterinaria , Polipéptido Amiloide de los Islotes Pancreáticos/sangre , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Pancreatitis/veterinaria , Animales , Estudios de Casos y Controles , Enfermedades de los Gatos/sangre , Gatos , Diabetes Mellitus/sangre , Diabetes Mellitus/metabolismo , Femenino , Masculino , Pancreatitis/sangre , Pancreatitis/metabolismo , Agregación Patológica de ProteínasRESUMEN
It was previously demonstrated that the methanol fraction of Sideroxylon obtusifolium (MFSOL) promoted anti-inflammatory and healing activity in excisional wounds. Thus, the present work investigated the healing effects of MFSOL on human keratinocyte cells (HaCaT) and experimental burn model injuries. HaCaT cells were used to study MFSOL's effect on cell migration and proliferation rates. Female Swiss mice were subjected to a second-degree superficial burn protocol and divided into four treatment groups: Vehicle, 1.0% silver sulfadiazine, and 0.5 or 1.0% MFSOL Cream (CrMFSOL). Samples were collected to quantify the inflammatory mediators, and histological analyses were performed after 3, 7, and 14 days. The results showed that MFSOL (50 μg/mL) stimulated HaCaT cells by increasing proliferation and migration rates. Moreover, 0.5% CrMFSOL attenuated myeloperoxidase (MPO) activity and also stimulated the release of interleukin (IL)-1β and IL-10 after 3 days of treatment. CrMFSOL (0.5%) also enhanced wound contraction, promoted improvement of tissue remodeling, and increased collagen production after 7 days and VEGF release after 14 days. Therefore, MFSOL stimulated human keratinocyte (HaCaT) cells and improved wound healing via modulation of inflammatory mediators of burn injuries.
Asunto(s)
Humanos , Femenino , Quemaduras/tratamiento farmacológico , Sapotaceae , Prolina , Queratinocitos , Hojas de la Planta , MetanolRESUMEN
Alveolar macrophages (AMs) are an essential part of defense mechanisms within the lungs and their phagocytic activity is important for organ homeostasis. The phagocytic ability of AMs obtained from bronchoalveolar lavage from 17 mature mixed-breed pleasure horses (8 healthy and 9 diagnosed with mild equine asthma) was studied through assays with Leishmania (Viannia) braziliensis promastigotes, which enabled the calculation of a phagocytic index (PI) and a survival index (SI). Results indicate that phagocytic activity of AMs in asthma affected horses is similar to healthy horses, while leishmanicidal activity is significantly increased in horses with asthma.(AU)
Os macrófagos alveolares (MAs) são uma parte essencial dos mecanismos de defesa dentro dos pulmões e sua atividade fagocítica é importante para a homeostase desse órgão. A capacidade fagocitária dos MAs obtidos do lavado broncoalveolar de 17 equinos adultos, sem raça definida (oito saudáveis e nove com diagnóstico de asma equina leve), foi estudada por meio de ensaios com promastigotas de Leishmania (Viannia) braziliensis. Foi calculado o índice fagocítico e o índice de sobrevivência. Os resultados indicam que a atividade fagocítica de MAs em cavalos com asma é semelhante a cavalos saudáveis, enquanto a atividade leishmanicida está significativamente aumentada em cavalos com essa enfermidade.(AU)
Asunto(s)
Animales , Asma/veterinaria , Leishmania braziliensis , Macrófagos Alveolares/parasitología , Caballos/parasitología , FagocitosisRESUMEN
Oral mucositis (OM) is a common and dose-limiting side effect of cancer treatment, including 5-fluorouracil (5-FU) and radiotherapy. The efficacy of the therapeutic measures to prevent OM is limited and disease prevention is not fully observable. Amifostine is a cytoprotective agent with a described anti-inflammatory potential. It is clinically used to reduce radiotherapy and chemotherapy-associated xerostomia. This study investigated the protective effect of amifostine on an experimental model of OM. Hamsters were divided into six groups: saline control group (5 mL/kg), mechanical trauma (scratches) of the right cheek pouch; 5-FU (60 and 40 mg/kg, ip, respectively, administered on days 1 and 2); amifostine (12.5, 25, or 50 mg/kg) + 5-FU + scratches. Salivation rate was assessed and the animals were euthanized on day 10 for the analysis of macroscopic and microscopic injury by scores. Tissue samples were harvested for the measurement of neutrophil infiltration and detection of inflammatory markers by ELISA and immunohistochemistry. 5-FU induced pronounced hyposalivation, which was prevented by amifostine (P<0.05). In addition, 5-FU injection caused pronounced tissue injury accompanied by increased neutrophil accumulation, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) tissue levels, and positive immunostaining for TNF-α, IL-1ß, and inducible nitric oxide synthase (iNOS). Interestingly, amifostine prevented the inflammatory reaction and consequently improved macroscopic and microscopic damage (P<0.05 vs 5-FU group). Amifostine reduced inflammation and protected against 5-FU-associated oral mucositis and hyposalivation.
Asunto(s)
Amifostina/uso terapéutico , Fluorouracilo/efectos adversos , Inflamación/prevención & control , Sustancias Protectoras/uso terapéutico , Estomatitis/prevención & control , Xerostomía/prevención & control , Animales , Cricetinae , Modelos Animales de Enfermedad , Inflamación/inducido químicamente , Inflamación/patología , Masculino , Estomatitis/inducido químicamente , Estomatitis/patología , Xerostomía/inducido químicamente , Xerostomía/patologíaRESUMEN
Oral mucositis (OM) is a common and dose-limiting side effect of cancer treatment, including 5-fluorouracil (5-FU) and radiotherapy. The efficacy of the therapeutic measures to prevent OM is limited and disease prevention is not fully observable. Amifostine is a cytoprotective agent with a described anti-inflammatory potential. It is clinically used to reduce radiotherapy and chemotherapy-associated xerostomia. This study investigated the protective effect of amifostine on an experimental model of OM. Hamsters were divided into six groups: saline control group (5 mL/kg), mechanical trauma (scratches) of the right cheek pouch; 5-FU (60 and 40 mg/kg, ip, respectively, administered on days 1 and 2); amifostine (12.5, 25, or 50 mg/kg) + 5-FU + scratches. Salivation rate was assessed and the animals were euthanized on day 10 for the analysis of macroscopic and microscopic injury by scores. Tissue samples were harvested for the measurement of neutrophil infiltration and detection of inflammatory markers by ELISA and immunohistochemistry. 5-FU induced pronounced hyposalivation, which was prevented by amifostine (P<0.05). In addition, 5-FU injection caused pronounced tissue injury accompanied by increased neutrophil accumulation, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) tissue levels, and positive immunostaining for TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Interestingly, amifostine prevented the inflammatory reaction and consequently improved macroscopic and microscopic damage (P<0.05 vs 5-FU group). Amifostine reduced inflammation and protected against 5-FU-associated oral mucositis and hyposalivation.
Asunto(s)
Animales , Masculino , Estomatitis/prevención & control , Xerostomía/prevención & control , Amifostina/uso terapéutico , Sustancias Protectoras/uso terapéutico , Fluorouracilo/efectos adversos , Inflamación/prevención & control , Estomatitis/inducido químicamente , Estomatitis/patología , Xerostomía/inducido químicamente , Xerostomía/patología , Cricetinae , Modelos Animales de Enfermedad , Inflamación/inducido químicamente , Inflamación/patologíaRESUMEN
A doença valvar crônica mitral (DVCM) é comum em cães e pode não causar sintomas clínicos da insuficiência cardíaca (IC) durante anos. O peptídeo natriurético tipo B (BNP) é armazenado nos miócitos ventriculares e secretado para circulação com seu fragmento NT-proBNP, quando ocorre aumento. Este estudo avaliou os níveis plasmáticos do peptídeo natriurético NT-proBNP em cães da raça Poodle em diferentes estágios da DVCM, seguindo as diretrizes do American College of Veterinary Internal Medicine (ACVIM, 2009). Amostras de sangue foram coletadas para determinação do biomarcador NT-proBNP para comparação entre grupos. As medianas do NT-proBNP nos grupos estudados foram: 551pmol/L (controle), 302pmol/L (grupo B1), 1.033pmol/L (grupo B2), 954pmol/L (grupo C) e 5.541pmol/L (grupo D). Mediante o uso de um ponto de corte ideal de >709pmol/L, foi possível identificar os cães com aumento cardíaco verdadeiro daqueles sem aumento cardíaco, com sensibilidade de 75% e especificidade de 100%. O NT-proBNP aumentou de acordo com o avanço dos estágios da DVCM, sendo os estágios B2, C e D aqueles com valores mais elevados desse biomarcador. Para o estágio B2, a mensuração do NT-proBNP mostrou ser uma excelente ferramenta para diagnosticar precocemente o aumento cardíaco em cães da raça Poodle.(AU)
Chronic mitral valve disease (CMVD) is common in dogs, it may not cause clinical symptoms of heart failure (HF) for years. The type B natriuretic peptide (BNP) is stored in the ventricular myocytes and secreted for circulation with its NT-proBNP fragment, when an increase occurs. This study evaluated the plasma levels of the NT-proBNP natriuretic peptide in Poodles at different stages of CMVD, following the guidelines of the American College of Veterinary Internal Medicine (ACVIM, 2009). Blood samples were collected for determination of NT-proBNP biomarker for comparison between groups. This median NT-proBNP in the studied groups were: 551pmol/L (Control), 302pmol/L (Group B1), 1,033pmol/L (Group B2), 954pmol/L (Group C) and 5,541pmol/L (Group D). Using an ideal cutoff of > 709pmol/L it was possible to identify dogs with true heart enlargement of those without a cardiac increase with sensitivity of 75% and specificity of 100%. NT-proBNP increased according to the progress of the stages of CMVD, being that stages B2, C and D, with the highest values of the biomarker. To stage B2, the NT-proBNP measurement proved to be an excellent tool for early diagnosis of cardiac enlargement in Poodles.(AU)
Asunto(s)
Animales , Perros , Perros/anomalías , Enfermedades de las Válvulas Cardíacas/veterinaria , Péptidos Natriuréticos/análisis , Membrana CelularRESUMEN
Linfoma multicêntrico apresenta alta prevalência dentre as neoplasias em cães, e o diagnóstico rotineiro não é eficaz para avaliação de prognóstico. A PCR para rearranjos de receptores de antígeno (PRRA) apresenta potencial para classificação e estadiamento de linfomas. Este trabalho objetiva relatar o desenvolvimento de um protocolo de PRRA para aplicação em cães, baseando-se em condições e primers descritos na literatura. Foram coletados aspirados de linfonodo de 10 cães com linfoma multicêntrico e 15 lâminas de linfonodo positivas para linfoma já secas ao ar, fixadas e coradas. O protocolo utilizado demonstrou-se eficaz na amplificação de DNA das amostras frescas e das lâminas, com sensibilidade de 75%, similar à de estudos anteriores. Resultados parciais sugerem prevalência de linfomas de células B (60%) sobre células T (40%). O presente estudo abre precedentes para uma série de novos estudos com diagnóstico molecular de linfomas.(AU)
Asunto(s)
Animales , Perros , Linfoma/clasificación , Linfoma/veterinaria , Receptores de Antígenos , Receptores de Antígenos de Linfocitos T gamma-delta , Técnicas de Diagnóstico Molecular/veterinariaRESUMEN
We investigated the association between bacterial vaginosis (BV) and human papillomavirus (HPV) infection in Papanicolaou smears in a Brazilian population. Cross-sectional analysis was performed on 673 samples collected from women attending public health centers in Olinda (PE, Brazil) by conventional cytology methodology and molecular analysis, PCR tests (GP5+/6+ and MY09/11). Cytological abnormalities, BV, and HPV-DNA were detected in 23 (3.4%) samples, 189 samples (28.1%), and 210 samples (31.2%), respectively. GP5+/6+ primers resulted in higher detection performance than MY09/11 primers, with 81% concordance between both primers (P < 0.0001). The occurrence of HPV-DNA and BV had ORs of 8.59 (P < 0.0001) and 2.91 (P = 0.0089) for abnormal cytology, respectively, whereas the concomitant presence of both infections showed an OR equal to 3.82 (P = 0.0054). Therefore, we observed an association between abnormal cervical cytology and HPV infection, BV, or both HPV infection and BV. These results highlight the necessity of monitoring patients presenting not only HPV, but also BV, as risk factors for cervical lesion development.
Asunto(s)
Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Vaginosis Bacteriana/microbiología , Vaginosis Bacteriana/patología , Adulto , Alphapapillomavirus/genética , Brasil/epidemiología , Estudios Transversales , ADN Viral , Femenino , Humanos , Persona de Mediana Edad , Oportunidad Relativa , Prueba de Papanicolaou , Infecciones por Papillomavirus/epidemiología , Vigilancia de la Población , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/patología , Vaginosis Bacteriana/epidemiología , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Atorvastatin (ATV) has bone anabolic properties, and alendronate (ALD) is an important antiresorptive drug. This study aimed to evaluate the effects of the combination of ALD and ATV on ligature-induced alveolar bone loss in rats. MATERIAL AND METHODS: Periodontitis was induced by ligature in 78 Wistar rats. Groups of six rats prophylactically received 0.9% saline (SAL), ALD (0.01 or 0.25 mg/kg subcutaneously) or ATV (0.3 or 27 mg/kg by gavage). Then, groups of six rats received the combination of ALD+ATV (0.25 mg/kg + 27 mg/kg, 0.01 mg/kg + 0.3 mg/kg, 0.25 mg/kg + 0.3 mg/kg or 0.01 mg/kg + 27 mg/kg) prophylactically. An extra group of six rats received therapeutic SAL or a lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) therapeutically. Three extra groups of six rats each received SAL or a lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) prophylactically or therapeutically for histometric and immunohistochemical analyses. The rats were killed on day 11 after ligature placement, and the maxillae were removed and processed for macroscopic, histomorphometric and TRAP immunohistochemical analyses. Gingival samples were collected to evaluate myeloperoxidase (MPO) activity. Blood samples were collected to measure serum bone-specific alkaline phosphatase (BALP) and transaminase levels and for hematological studies. Rats were weighed daily. RESULTS: All combined therapies prevented alveolar bone loss when compared with SAL or low doses of monotherapy (ALD or ATV) (p < 0.05). The lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively), administered either prophylactically (39.0%) or therapeutically (53.5%), prevented alveolar bone loss. Decreases in bone and cementum resorption, in leukocyte infiltration and in immunostaining for TRAP and MPO activity corroborated the morphometric findings. The lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) prevented BALP reduction (p < 0.05) and did not alter the level of serum transaminases. Moreover, the lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) also reduced neutrophilia and lymphomonocytosis and did not cause weight loss when compared with administration of SAL. CONCLUSION: The lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) demonstrated a protective effect on alveolar bone loss.
Asunto(s)
Alendronato/administración & dosificación , Pérdida de Hueso Alveolar/prevención & control , Conservadores de la Densidad Ósea/administración & dosificación , Ácidos Heptanoicos/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Pirroles/administración & dosificación , Fosfatasa Ácida/análisis , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Aspartato Aminotransferasas/sangre , Atorvastatina , Peso Corporal , Cemento Dental/efectos de los fármacos , Encía/enzimología , Infusiones Parenterales , Inyecciones Subcutáneas , Isoenzimas/análisis , Trastornos Leucocíticos/prevención & control , Leucocitos/efectos de los fármacos , Leucocitosis/prevención & control , Masculino , Monocitos/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Peroxidasa/análisis , Ratas Wistar , Resorción Radicular/prevención & control , Fosfatasa Ácida TartratorresistenteRESUMEN
PURPOSE: Oral mucositis (OM) is a frequent side effect in patients with cancer. We investigate the effect of atorvastatin (ATV), a cholesterol-lowering drug, on OM induced by 5-fluorouracil (5-FU) in hamsters. METHODS: OM was induced by the i.p. administration of 5-FU, with excoriations of the cheek pouch mucosa. The animals were pretreated with i.p. ATV 1, 5 or 10 mg/kg or vehicle (saline and 5% (vol/vol) ethanol) 30 min before 5-FU injection and daily for 5 or 10 days. Samples of cheek pouches and main organs were removed for histopathological analysis, determination of TNF-α, IL-1ß, nitrite, non-protein sulfhydryl group (NP-SH) levels, myeloperoxidase (MPO) assay and immunohistochemistry for induced nitric oxide synthase (iNOS). Blood was collected for a leukogram analysis of biochemical parameters and analysis of bacteremia. RESULTS: ATV at doses of 1 and 5 mg/kg reduced mucosal damage and inflammation, as well as the levels of cytokines, nitrite and myeloperoxidase activity on the 5th and 10th day of OM and immunostaining for iNOS on the 5th day of OM.ATV at 1 mg/kg increased cheek pouch NP-SH when compared to 5-FU groups on the 10th day of OM. The association between ATV 5 mg/kg and 5-FU decreased the survival rate, amplified the leukopenia of animals, increased transaminase serum levels and caused liver lesions. We also detected the presence of Gram-negative bacillus in the blood of 100% of the animals treated with ATV 5 mg/kg + 5-FU. CONCLUSIONS: Atorvastatin prevented mucosal damage and inflammation associated with 5-FU-induced OM, but the association of a higher dose of ATV with 5-FU induced hepatotoxicity and amplified leukopenia.
Asunto(s)
Antiinflamatorios no Esteroideos/toxicidad , Antimetabolitos Antineoplásicos/toxicidad , Fluorouracilo/toxicidad , Ácidos Heptanoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Pirroles/uso terapéutico , Estomatitis/tratamiento farmacológico , Animales , Atorvastatina , Bacteriemia/inducido químicamente , Bacteriemia/microbiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Cricetinae , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Ácidos Heptanoicos/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Leucopenia/inducido químicamente , Masculino , Mesocricetus , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/patología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Nitritos/metabolismo , Peroxidasa/metabolismo , Pirroles/efectos adversos , Estomatitis/inducido químicamente , Estomatitis/patología , Compuestos de Sulfhidrilo/metabolismoRESUMEN
OBJECTIVES: To study and characterize the in vivo effect of the lectin from Luetzelburgia auriculata seed on acute inflammation models. METHODS: The lectin was purified from the crude saline extract by affinity chromatography on a guar-gum matrix. Native, heat-treated, and digested lectin was evaluated for anti-inflammatory activity by using peritonitis and paw edema models. The anti-inflammatory activity was characterized by intravital microscopy, nitric oxide production, and myeloperoxidase activity. RESULTS: The lectin exhibited anti-inflammatory activity (2 mg/kg) on both models, reducing local myeloperoxidase activity. Galactose or heat treatment (100 degrees C, 10 min) reduced anti-inflammatory action. Anti-inflammation involves the inhibition of adhesion and rolling of leukocytes along with augmentation of nitric oxide in serum. The lectin inhibited the edematogenic effect of histamine and prostaglandins (PGE2) but did not alter the chemoattractant effect of IL-8. CONCLUSIONS: The results indicate that this lectin is a potent anti-inflammatory molecule. Its effects engage diverse modulatory events.
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Antiinflamatorios no Esteroideos/farmacología , Adhesión Celular/efectos de los fármacos , Dinoprostona/antagonistas & inhibidores , Fabaceae/química , Antagonistas de los Receptores Histamínicos , Inflamación/tratamiento farmacológico , Rodamiento de Leucocito/efectos de los fármacos , Leucocitos/efectos de los fármacos , Lectinas de Plantas/farmacología , Animales , Antiinflamatorios no Esteroideos/química , Carragenina , Quimiotaxis de Leucocito/efectos de los fármacos , Dinoprostona/farmacología , Edema/inducido químicamente , Edema/prevención & control , Electroforesis en Gel de Poliacrilamida , Galactosa/metabolismo , Indicadores y Reactivos , Inflamación/enzimología , Inflamación/patología , Neutrófilos/efectos de los fármacos , Óxido Nítrico/metabolismo , Peritonitis/inducido químicamente , Peritonitis/tratamiento farmacológico , Peroxidasa/metabolismo , Lectinas de Plantas/química , Ratas , Ratas Wistar , Semillas/químicaRESUMEN
Immunological and allergenic responses against the latex of Calotropis procera were investigated in mice by oral and subcutaneous routes. The latex was fractionated according to water solubility and molecular size of its components. The fractions were named as non-dialyzable latex (NDL) corresponding to the major latex proteins, dialyzable latex (DL) corresponding to low molecular size substances and rubber latex (RL) which was highly insoluble in water. Anti-sera against these fractions were assayed for total IgG and IgA titration by ELISA and IgE and IgG(1) were quantified by passive cutaneous anaphylaxis (PCA) in rats and mice, respectively. None of the fractions induced antibodies level increases when mice received latex fractions by oral route and thus, did not develop allergy. Nonetheless, anti-sera of mice sensitized with NDL and RL by subcutaneous route displayed considerable immunological response while DL did not. IgG level augmented consistently against NDL and RL while IgA response was detected only to NDL. NDL and RL induced very strong PCA reactions suggesting that both fractions would contain latex substances involved in allergy. Furthermore, protein analysis of NDL and RL suggests that RL still retain residual proteins abundantly found in NDL that could explain its similar allergenic effect. No IgG(1) reaction was detected in any of the anti-sera tested. According to the results, the proteins of latex of Calotropis procera can provoke allergy by subcutaneous route. The NDL has previously shown to display anti-inflammatory and analgesic activities by intraperitoneal injection. It should be relevant to determine whether NDL could induce such activities when assayed by oral route since it was ineffective to induce allergy by this way.
Asunto(s)
Formación de Anticuerpos , Antígenos de Plantas/administración & dosificación , Antígenos de Plantas/farmacología , Calotropis , Hipersensibilidad al Látex/inmunología , Látex/administración & dosificación , Látex/inmunología , Administración Oral , Animales , Antígenos de Plantas/química , Brasil , Fraccionamiento Químico , Relación Dosis-Respuesta Inmunológica , Ensayo de Inmunoadsorción Enzimática , Inmunización , Inmunoglobulina A/sangre , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Inyecciones Subcutáneas , Látex/química , Masculino , Ratones , Peso Molecular , Anafilaxis Cutánea Pasiva , Extractos Vegetales/administración & dosificación , Extractos Vegetales/inmunología , Ratas , Solubilidad , Solventes/química , Factores de Tiempo , Agua/químicaRESUMEN
OBJECTIVES AND DESIGN: Previous studies have described pro- and anti-inflammatory activities displayed by the latex from Calotropis procera. This report aims to clarify these observations and shows that such activities can be segregated from the whole latex. METHODS: The latex was divided into water-soluble fractions devoid of poly-isoprene by centrifugation and dialysis and both the activities were assayed by the peritonitis model in rats. The drugs dexamethasone, thalidomide, meclizine, indomethacin and celecoxib were used to modulate the inflammatory stimuli. RESULTS: Inflammation in rats was observed 2 h after intraperitoneal administration of the stimulus (DL fraction) in a dose dependent manner. This activity was inhibited by previous intravenous injection of dexamethasone, thalidomide and meclizine. Indomethacin and celecoxib did not reverse inflammation. These results suggest the involvement of histamine release and TNF-alpha mediated inflammation while prostaglandins seem not to be required. The anti-inflammatory fraction (NDL) inhibited inflammation triggered by proinflammatory fraction (DL) suggesting that NDL ought to follow a similar pathway of action to that of the anti-inflammatory drugs that were able to inhibit inflammation triggered by DL. CONCLUSIONS: Pro- and anti-inflammatory activities of the latex are displayed by compounds suitable to be fractionated on the basis of their molecular size.
Asunto(s)
Calotropis , Látex , Animales , Antiinflamatorios/farmacología , Ratas Wistar , Diálisis RenalRESUMEN
We have investigated the anti-inflammatory and antimicrobial effect of the lectin from Lonchocarpus sericeus seeds (LSL) in a model of infectious peritonitis in adult Wistar rats. Animals were treated with saline or LSL (10 mg kg(-1), i.v) immediately and 6 h after the induction of peritonitis via cecal ligation and single puncture. Twelve hours after surgery, animals were killed and the infectious process was monitored by total and differential count of cells from blood and peritoneal washing liquid, adenosine deaminase activity, antibiogram and the number of viable bacteria of the peritoneal cavity. LSL treatment decreased the inflammatory response evoked by the induction of peritonitis, as seen by the inhibition of neutrophil migration into peritoneal cavities, leucocytosis and reduction of adenosine deaminase activity in the peritoneal fluid. All these effects were reversed by the lectin association to N-acetyl-glucosamine. LSL in-vitro did not show any antimicrobial action, but promoted a marked decrease of the viable bacterial population in peritoneal cavities. In conclusion, LSL inhibited the inflammatory response and the bacterial colonization of infectious peritonitis in rats.
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Derris/química , Peritonitis/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Bacterias/efectos de los fármacos , Bacterias/genética , Movimiento Celular , Inflamación , Lectinas , Masculino , Neutrófilos/efectos de los fármacos , Neutrófilos/fisiología , Peritonitis/veterinaria , Ratas , Ratas Wistar , Semillas/químicaRESUMEN
PAL is a glucose/mannose-specific lectin isolated from Pisum arvense seeds. Previously, we demonstrated the capacity of other leguminous lectins to induce oedema formation and neutrophil stimulation. To investigate the potential pro-inflammatory activity of PAL, we have studied its ability to induce neutrophil migration into peritoneal cavities of rats and neutrophil chemotaxis in-vitro. The role of resident cells and sugar residues on PAL activity was analysed. PAL or saline (control) were administered intraperitoneally to rats, and total and differential leucocyte (macrophages, neutrophils and mast cells) counts were performed. The role of resident cells on the PAL effect was evaluated using three strategies: reducing the total resident cell population by lavage of rat cavities with saline; increasing macrophage population by treating animals with thioglycolate; and depleting mast cell population by subchronic treatment of rats with compound 48/80. PAL induced in-vitro and in-vivo neutrophil migration. In-vivo, PAL (50, 100, 200 and 300 microg) significantly (P < 0.05) and dose-dependently increased neutrophil migration by 600, 740, 900 and 940%, respectively, showing maximal effect 4 h after injection. PAL induced mononuclear cell migration. The neutrophil stimulatory effect of PAL was potentiated in animals treated with both thioglycolate and compound 48/ 80. The indirect lectin chemotactic effect was shown in rats injected with supernatant from cultured macrophages stimulated by PAL. In conclusion, PAL was shown to exhibit in-vivo and in-vitro proinflammatory activity. The in-vivo effect seemed to occur by a dual mechanism that was independent, but also dependent, on resident cells.