RESUMEN
PURPOSE: To examine the effects of a negatively charged nanostructured curcumin microemulsion in experimental ulcerative colitis (UC) in rats. METHODS: Four percent acetic acid was used to induce UC. The animals were treated for seven days and randomly assigned to four groups: normal control (NC), colitis/normal saline (COL/NS), colitis/curcumin (COL/CUR), and colitis/mesalazine (COL/MES). The nanostructured curcumin was formulated with a negative zeta potential (-16.70 ± 1.66 mV). Dosage of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 1-ß (IL-1ß), interleukin 6 (IL-6), and antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase), macro and microscopic evaluation of the colon tissue were analyzed. RESULTS: The COL/CUR group had a higher level of antioxidant enzymes compared to the COL/MESgroup. The levels of TNF-α, IL-1ß and IL-6 were significantly lower in the colonic tissue of the COL/CUR group rats, when compared to the COL/NS and COL/MES groups (p < 0.001). The presence of ulcers in the colonic mucosa in rats of the COL/NSgroup was significantly higher than in the COL/MES group (p < 0.001). In the NC and COL/CUR groups, there were no ulcers in the colonic mucosa. CONCLUSIONS: The nanostructured microemulsion of curcumin, used orally, positively influenced the results of the treatment of UC in rats. The data also suggests that nanostructured curcumin with negative zeta potential is a promising phytopharmaceutical oral delivery system for UC therapy. Further research needs to be done to better understand the mechanisms of the negatively charged nanostructured curcumin microemulsion in UC therapy.
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Colitis Ulcerosa , Colitis , Curcumina , Animales , Ratas , Antioxidantes/farmacología , Colitis/patología , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Colon/patología , Curcumina/farmacología , Interleucina-6 , Factor de Necrosis Tumoral alfaRESUMEN
PURPOSE: The colon and ileum play significant roles on liver physiology. Studies about simultaneous hepatectomy and colectomy or enterectomy are scarce and controversial. We investigated and compared the effects of ileum and colon resection on liver regeneration. MATERIALS AND METHODS: Twenty four Wistar rats were allocated in group I-(sham), group II-70% hepatectomy; group III-70% hepatectomy + ileal resection, and group IV-70% hepatectomy + partial colectomy. On the sixth day, serum hepatic enzymes, albumin, hepatocyte growth-factor (HGF) and transforming growth factor-alpha (TGF-α) were measured. The hepatic regeneration rate was estimated. Ki-67 immunohistochemical analysis was done in remnant liver. RESULTS: Hepatic enzymes levels were significantly higher in group III rats comparing to the other groups (p < 0.001). In group IV, the levels were significantly lower than in groups II and III (p < 0.001). Albuminemia was significantly lower in group III rats comparing with the other groups (p < 0.001). Albuminemia was not different comparing groups I and IV (p > 0.05). Cytokines HGF and TGF-α levels in group IV were significantly higher than in the other groups (p < 0.001). Liver regeneration rate was higher group IV than in groups II and III, and the difference was statistically significant (p = 0.002). The hepatocytes expression of Ki-67 was significantly higher in the remnant liver of group IV than in group III (p = 0.002). There was no difference in Ki-67 expression between groups II and IV (p > 0.05). CONCLUSION: Ileum and colon resection have different effects on liver regeneration. Colon resection positively influences liver regeneration, while ileum resection negatively influences the regenerative process, in a rat model.
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Hepatectomía , Regeneración Hepática , Animales , Colon/cirugía , Íleon/cirugía , Hígado/cirugía , Ratas , Ratas WistarRESUMEN
PURPOSE: The objective of this study was to investigate the accuracy of 18F-FDG-PET in the diagnosis of multibacterial abdominal sepsis by cecum ligation and puncture (CLP) in rats. METHODS: Adult Wistar rats ( Rattus norvegicus ), weighing 227±35g, were allocated into a sepsis group by CLP (n=10) and sham group (n=10). 18F-FDG-PET using microPET was performed on all rats after 24 hours. RESULTS: All animals survived for postoperative 24h. The abdomen/liver ratio of the standardized uptake value (SUV) percentage was significantly higher in the sepsis group than in the sham (p=0.004). The ROC curve showed an accuracy of 18F-FDG-PET to detect abdominal sepsis of 88.9% (p=0.001), sensitivity of 90% and specificity of 88.9%. When a cut-off point of 79% of the ratio between the SUV on the abdominal region and liver was established, the sensitivity was 90%, specificity of 88.9%; positive and negative predictive values of 90.0% and 88.9%, respectively. CONCLUSIONS: The diagnostic accuracy of 18F-FDG-PET in rats with abdominal sepsis was significantly high. It was also demonstrated the predictive ability of the abdomen/liver SUV ratio to diagnose abdominal sepsis. These findings may have implications for the clinical setting, locating septic foci with PETscan.
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Fluorodesoxiglucosa F18 , Infecciones Intraabdominales/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Sepsis/diagnóstico por imagen , Animales , Infecciones Intraabdominales/patología , Valor Predictivo de las Pruebas , Ratas , Ratas Wistar , Valores de Referencia , Reproducibilidad de los Resultados , Sepsis/patología , Factores de TiempoRESUMEN
PURPOSE: To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced breast cancer model in Wistar rats. METHODS: We compared the response of breast cancer to the oral administration of A. chica extract (ACE) for 16 weeks, associated or not with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500µg/kg injected i.p; DMBA+ACE+Vincristine 250µg/kg i.p. Imaging by microPET and fluorescence, biochemistry, oxidative stress, hematology and histopathology were used to validate the treatments. RESULTS: All animals survived. A gradual weight gain in all groups was observed, with no significant difference (p>0.05). The oral administration of ACE and ACE+vincristine 50% significantly reduced breast tumors incidence examined with PET-18FDG and fluorescence (p<0.001). Significant reduction of serum transaminases, oxidative stress and hematological toxicity were observed in these groups. Antioxidant enzyme levels in breast tissue were significantly higher compared to the DMBA and DMBA+vincristine groups. CONCLUSION: These results demonstrate for the first time that ACE positively influences the treatment of DMBA-induced breast cancer in animal model, inducing a reduction in oxidative stress and chemotherapy toxicity, meaning that ACE may have clinical implication in further studies.
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Antineoplásicos/farmacología , Bignoniaceae/química , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Neoplasias Experimentales/tratamiento farmacológico , Extractos Vegetales/farmacología , 9,10-Dimetil-1,2-benzantraceno , Animales , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Carcinógenos , Carcinoma/diagnóstico por imagen , Carcinoma/patología , Catalasa/análisis , Femenino , Fluorodesoxiglucosa F18 , Glutatión Peroxidasa/análisis , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/patología , Imagen Óptica/métodos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Ratas Wistar , Reproducibilidad de los Resultados , Superóxido Dismutasa/análisis , Factores de Tiempo , Resultado del Tratamiento , Vincristina/farmacología , Vincristina/uso terapéuticoRESUMEN
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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Antiinflamatorios/uso terapéutico , Fluorouracilo/efectos adversos , Mucositis/prevención & control , Simvastatina/uso terapéutico , Animales , Biomarcadores/sangre , Modelos Animales de Enfermedad , Interleucina-1beta/sangre , Interleucina-6/sangre , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Masculino , Mucositis/inducido químicamente , Mucositis/patología , Distribución Aleatoria , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND: The value of drain amylase on the first postoperative day after pancreatic resections has been described as an efficient predictor of pancreatic fistula. In spite of this, the cut-off point below which the drains can be removed early remains controversial. AIM: Validate the use of the amylase on the 1st postoperative day in the correlation with pancreatic fistula and define the value at which early drain removal is safe. METHOD: Were included patients undergoing Whipple surgery in the period of 2007 to 2016. Group 1 enrolled the ones who did not develop fistula and those who developed biochemical fistula for less than seven days postoperatively and group 2 included patients who developed persistent biochemical fistula between seven and 21 days and those with grade B and C fistula. RESULTS: Sixty-one patients were included, 41 comprised group 1 and 20 group 2. The incidence of abdominal collections, need for reoperation and time of hospitalization were for group 1 and 2, respectively: 17.1%, 17.1% and 9.5 days, and 65%, 40% and 21.1 days. The median of the amylase from the drain at 1st postoperative day was in group 1 and 2, respectively: 175 U/l and 3172.5 U/l (p=0.001). Using a cut-off of 180 to predict the group to which the patient would belong there was obtained sensitivity, specificity, positive predictive value and negative predictive value of 100%, 48.8%, 50% and 100% respectively. CONCLUSION: It was validated the cut-off value of 180 U/l as appropriate to early drain removal.
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Amilasas , Drenaje , Fístula Pancreática/diagnóstico , Pancreaticoduodenectomía , Cuidados Posoperatorios/métodos , Complicaciones Posoperatorias/diagnóstico , Amilasas/análisis , Amilasas/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios ProspectivosRESUMEN
PURPOSE: To evaluate if Moringa oleifera leaf aqueous extract (ME) influences the healing of skin wounds of diabetic rats. METHODS: Wistar rats were used (6 rats/group). Group 1 received normal saline (NS) v.o. Group 2 received moringa extract (100mg/kg v.o) for 3 weeks. Groups 3 and 4: Streptozotocin (STZ) induced diabetes. Group 3 received NS; Group 4 received aqueous ME (100mg/kg) v.o.The wounds of groups 1 and 3 rats were topically treated with NS; wounds of groups 2 and 4 treated with 200µL of 10% ME. After anesthesia, all rats had skin square excision wounds 1.5cm2. Wound percent contractions were measured. On 10th day, blood glucose and serum cytokines were measured. Histometry of wounds was studied using ImagePro6.0 software. RESULTS: Glycemia was significantly reduced in ME treated rats. These rats had higher percent contraction of the wounds on 2nd, 5th and 10th days, then controls (p<0.05). Diabetic rats treated with NS had TNF-α, IL-1ß and IL-6 expression higher than in rats receiving ME. The histopathological score of ME treated diabetic rats (198±13.7) was significantly higher than treatment with NS (145±10.5). CONCLUSION: ME extract positively influenced healing of wounds in diabetic rats after systemic and topical treatment.
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Moringa oleifera/química , Extractos Vegetales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Administración Tópica , Animales , Diabetes Mellitus Experimental , Interleucina-2/sangre , Interleucina-6/sangre , Ratas , Ratas Wistar , Estreptozocina , Factor de Necrosis Tumoral alfa/sangreRESUMEN
After total gastrectomy, the ileocecal graft may act as a reservoir and protect against reflux but give rise to transposition of the ileum and cause possible changes in bile acid metabolism and nutrition. This study compared the ileocecal graft and jejunal pouch. Male Wistar rats weighing 265 +/- 22 g were submitted to sham operation (S), ileocecal interposition graft (IIG), and jejunal pouch interposition graft (JP) after total gastrectomy. Eight weeks later, the esophagus was examined for evidence of esophagitis. Nutritional biochemistry and weight profile were documented preoperatively and 8 weeks after surgery. The oral glucose tolerance test was performed. Thirty-three rats were operated on and 30 survived for 8 weeks. Esophagitis occurred in seven JP rats. Body weight was significantly higher in IIG than in JP rats (p < .05). Normal glucose tolerance to intragastric glucose load was observed in sham and operated rats. JP rats had a significant decrease in serum albumin, glucose, transferrin, hemoglobin, iron, folate, and calcium, compared to sham (p < .05). Cobalamine was significantly lower in IIG rats than in JP rats (p < .05). In the IIG and JP groups, serum/hepatic total bile acid did not differ significantly from preoperative and sham values. In conclusion, the IIG interposition graft in rats prevented esophagitis, preserved nutrition, and did not interfere with enterohepatic total bile acid circulation.
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Gastrectomía/métodos , Válvula Ileocecal/trasplante , Yeyuno/trasplante , Síndromes Posgastrectomía/prevención & control , Trasplante Heterotópico , Anastomosis Quirúrgica , Animales , Ácidos y Sales Biliares/metabolismo , Peso Corporal , Calcio/sangre , Duodeno/cirugía , Circulación Enterohepática , Esofagitis Péptica/prevención & control , Esófago/cirugía , Ácido Fólico/sangre , Reflujo Gastroesofágico/prevención & control , Prueba de Tolerancia a la Glucosa , Hemoglobinas/análisis , Hipocalcemia/etiología , Absorción Intestinal , Lípidos/sangre , Masculino , Complicaciones Posoperatorias/prevención & control , Ratas , Ratas Wistar , Transferrina/análisis , Vitamina B 12/sangreRESUMEN
PURPOSE: To evaluate the biodistribution of sodium pertecnetate (Na(99m)TcO(4)) in organs and tissues, the morphometry of remnant intestinal mucosa and ponderal evolution in rats subjected to massive resection of the small intestine. METHODS: Twenty-one Wistar rats were randomly divided into three groups of 7 animals each. The short bowel (SB) group was subjected to massive resection of the small intestine; the control group (C) rats were not operated on, and soft intestinal handling was performed in sham rats. The animals were weighed weekly. On the 30th postoperative day, 0.l mL of Na(99m)TcO(4), with mean activity of 0.66 MBq was injected intravenously into the orbital plexus. After 30 minutes, the rats were killed with an overdose of anesthetic, and fragments of the liver, spleen, pancreas, stomach, duodenum, small intestine, thyroid, lung, heart, kidney, bladder, muscle, femur and brain were harvested. The biopsies were washed with 0.9% NaCl.,The radioactivity was counted using Gama Counter Wizard 1470, PerkinElmer. The percentage of radioactivity per gram of tissue (%ATI/g) was calculated. Biopsies of the remaining jejunum were analysed by HE staining to obtain mucosal thickness. Analysis of variance (ANOVA) and the Tukey test for multiple comparisons were used, considering p<0.05 as significant. RESULTS: There were no significant differences in %ATI/g of the Na(99m)TcO(4) in the organs of the groups studied (p>0.05). An increase in the weight of the SB rats was observed after the second postoperative week. The jejunal mucosal thickness of the SB rats was significantly greater than that of C and sham rats (p<0.05). CONCLUSION: In rats with experimentally-produced short bowel syndrome, an adaptive response by the intestinal mucosa reduced weight loss. The biodistribution of Na(99m)TcO(4) was not affected by massive intestinal resection, suggesting that short bowel syndrome is not the cause of misleading interpretation, if an examination using this radiopharmaceutical is indicated.
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Intestino Delgado/cirugía , Radiofármacos/farmacocinética , Síndrome del Intestino Corto/metabolismo , Pertecnetato de Sodio Tc 99m/farmacocinética , Animales , Modelos Animales de Enfermedad , Mucosa Intestinal/patología , Intestino Delgado/patología , Distribución Aleatoria , Ratas , Ratas Wistar , Distribución TisularRESUMEN
PURPOSE: The infection is one of the main factors that affect the physiological evolution of the surgical wounds. The aim of this work is to evaluate the effects of fibroblast growth factor (FGFâ) and anti-FGFâ in the healing, synthesis and maturation of collagen when topically used on infected skin wounds of rats. METHODS: An experimental study was performed in 60 male Wistar rats. All animals were divided in two groups (A and B). Each group was divided in three subgroups A1, B1; A2, B2 and A3, B3. After anesthesia with pentobarbital, two open squared wounds (1cm(2)), 4 cm distant to each other, were done in the dorsal skin of all the rats. In group A (n=30) the wounds were contaminated with multibacterial standard solution, and in group B(n=30) the wounds were maintained sterile. These wounds were named F1 (for inflammation analysis) and F2 (for collagen study). The open wounds of A1 and B1 rats were topically treated with saline solution, A2 and B2 were treated with FGFâ and subgroups A3 and B3 were treated with FGFâ and anti-FGFâ. The rats were observed until complete epitelization of F2 wounds for determination of healing time and the expression of types I and III collagen, using Picro Sirius Red staining. Inflammatory reaction in F1 wounds was studied using hematoxilineosin staining. The three variable was measured by the Image Pro-Plus Média Cybernetics software. The statistical analysis was performed by ANOVA and Tukey test, considering p<0.05 as significant. RESULTS: It was observed that infection retarded significantly (p<0.05) the time of wound scarring and the topical application of FCFb reverted the inhibition of healing caused by bacteria. The inflammatory reaction was greater in the subgroup B2 than in B1 and A3, and the difference was significant (p<0.05). It was observed greater expression of type I collagen in all the subgroups treated with FCFb, when compared with the untreated subgroups. Type III collagen was significantly decreased in wounds of B3 rats, comparing to the other subgroups. CONCLUSIONS: The FCFb accelerated the healing of open infected wounds and contributed with maturation of collagen, enhancing the type I collagen density. The anti-FCFb antibody was able to attenuate the production of both type I and III collagen.
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Colágeno/metabolismo , Factor 2 de Crecimiento de Fibroblastos/uso terapéutico , Fibroblastos/fisiología , Infección de la Herida Quirúrgica/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Análisis de Varianza , Animales , Colágeno/farmacología , Inflamación/fisiopatología , Masculino , Ratas , Ratas Wistar , Piel/patología , Cloruro de Sodio , Resistencia a la Tracción , Factores de TiempoRESUMEN
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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Colectomía , Colon/fisiología , Hepatectomía , Regeneración Hepática/fisiología , Animales , Masculino , Ratas , Ratas WistarRESUMEN
PURPOSE:: To examine a correlation of micro-PET images with photographic images of the digestive organs in abdominal sepsis model. METHODS:: Male Wistar rats weighing 265±18g were used. Abdominal sepsis was induced by ligature and cecal puncture. Micro-PET Images from abdominal cavity septic foci were obtained using 18-Fluoro-deoxyglucose, looking for a correlation with photographic images of abdominal cavity organs. Pearson's correlation test was used. RESULTS:: The mean standard uptake values (SUV) and lesion areas were 2.58±0.63SUVbwg/ml and 546.87±300.95mm2, respectively. There was a strong positive correlation between the two variables (r=0.863, p=0.137), which resulted in a coefficient of determination r2?0.75, meaning that 75% of SUV variation is explained by the lesion areas of digestive organs. CONCLUSION:: Micro-PET allows high throughput assessment of lesion count and volume in pre-clinical rat model of CPL abdominal sepsis.
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Fluorodesoxiglucosa F18 , Infecciones Intraabdominales/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Sepsis/diagnóstico por imagen , Animales , Sistema Digestivo/diagnóstico por imagen , Sistema Digestivo/patología , Modelos Animales de Enfermedad , Infecciones Intraabdominales/patología , Masculino , Fotograbar/métodos , Ratas Wistar , Reproducibilidad de los Resultados , Sepsis/patología , Factores de TiempoRESUMEN
PURPOSE: To evaluate the effect of tadalafil in renal ischemia/reperfusion (I/R) injury in rats Methods: Group I/R saline rats (n=6) were subjected to 45 minutes of left renal ischemia and treated with saline; the I/R tadalafil rats (n=6) received oral 10mg/kg tadalafil microemulsion one hour before ischemia. In both groups, 8 hours after ischemia, laboratory analysis were performed Results: Better tissue perfusion was lower in ischemic left/kidney than in right/kidney in saline group, suggesting reduced kidney clearance. Fluorescence in left/kidneys of tadalafil treated rats was lower than in right/kidneys (difference not significant). The fluorescence signal intensity in kidneys of tadafil treated rats was higher than in saline rats. TNF-α levels were significantly lower in I/R tadalafil group rats compared to I/R saline group (154±10.3 vs 391.3±12.3), as well as IL-1ß (163.4±13.2 vs 279±11.5pg/dL), and IL-6 (122.9±8.1 vs 173.7±6.3 respectively; p=0.0001). Urea, creatinine and C-reactive protein were significantly lower in tadafil treated rats then in saline group Conclusion: Tadalafil therapy decreased the expression of circulating pro-inflammatory cytokines in a renal I/R rodent model, while improving kidney function proofs.
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Riñón/efectos de los fármacos , Daño por Reperfusión/prevención & control , Tadalafilo/farmacología , Vasodilatadores/farmacología , Animales , Citocinas , Fluorescencia , Riñón/lesiones , Modelos Animales , Ratas , Ratas Wistar , Daño por Reperfusión/sangreRESUMEN
PURPOSE:: To evaluate the effect of oxacillin bonded to magnetic nanoparticles in local infection model in rat. METHODS:: Twelve Wistar rats weighing 290±18g were randomly divided into four groups (n=6, each) and all rats had a magnet ring sutured on their right thighs. In the biodistribution group rats 0.1mL of 99mTc-magnetite (0.66 MBq) was injected i.v and after 30 minutes, biodistribution of 99mTc-magnetite was evaluated in right and left thighs. The other groups were inoculated with MRSA in each thigh muscles. Group 1 rats were injected i.v. with magnetite, group 2 with Magnetite + Oxacillin, group 3 with saline twice a day. After 24 hours samples of muscle secretion were harvested for microbiological analysis; muscle, lungs and kidneys for histology. RESULTS:: 99mTc-magnetite uptake was three-fold higher in right thigh muscles (with external magnet) than in the left. In magnetite and oxacillin-magnetite groups, bacterial/CFU was significantly lower in thigh muscles than in saline-controls. The inflammatory reaction in muscles and lungs was significantly lower in oxacillin-magnetite group-rats than in other groups (p<0.001) . CONCLUSION:: This study confirms the potential antimicrobial activity of magnetic nanoparticles for Methicillin-Resistant S. aureus strains, which in addition to concentrate the antibiotic at the infection site, positively influenced the treatment.
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Antibacterianos/administración & dosificación , Nanopartículas de Magnetita/administración & dosificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Oxacilina/administración & dosificación , Infecciones Estafilocócicas/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Nanopartículas , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
BACKGROUND: [corrected] There is substantial evidence that infection with Helicobacter pylori plays a role in the development of gastric cancer and that it is rarely found in gastric biopsy of atrophic gastritis and gastric cancer. On advanced gastric tumors, the bacteria can be lost from the stomach. AIMS: To analyze the hypothesis that the prevalence of H.pylori in operated advanced gastric carcinomas and adjacent non-tumor tissues is high, comparing intestinal and diffuse tumors according to Lauren's classification METHODS: A prospective controlled study enrolled 56 patients from "Hospital Universitário", Federal University of Rio Grande do Norte, Natal, RN, Brazil, with advanced gastric cancer, treated from February 2000 to March 2003. Immediately after partial gastrectomy, the resected stomach was opened and several mucosal biopsy samples were taken from the gastric tumor and from the adjacent mucosa within 4 cm distance from the tumor margin. Tissue sections were stained with hematoxylin and eosin. Lauren's classification for gastric cancer was used, to analyse the prevalence of H. pylori in intestinal or diffuse carcinomas assessed by the urease rapid test, IgG by ELISA and Giemsa staining. H. pylori infected patients were treated with omeprazole, clarithromycin and amoxicillin for 7 days. Follow-up endoscopy and serology were performed 6 months after treatment to determine successful eradication of H. pylori in non-tumor tissue. Thereafter, follow-up endoscopies were scheduled annually. Chi-square and MacNemar tests with 0.05 significance were used. RESULTS: Thirty-four tumors (60.7%) were intestinal-type and 22 (39.3%) diffuse type carcinomas. In adjacent non-tumor gastric mucosa, chronic gastritis were found in 53 cases (94.6%) and atrophic mucosa in 36 patients (64.3%). All the patients with atrophic mucosa were H. pylori positive. When examined by Giemsa and urease test, H. pylori positive rate in tumor tissue of intestinal type carcinomas was higher than that in diffuse carcinomas. In tumor tissues, 34 (60.7%) H. pylori-positive in gastric carcinomas were detected by Giemsa method. H. pylori was observed in 30 of 56 cases (53.5%) in tissues 4 cm adjacent to tumors. This difference was not significant. Eradication of H. pylori in non-tumor tissue of gastric remnant led to a complete negativity on the 12th postoperative month CONCLUSIONS: The data confirmed the hypothesis of a high prevalence of H. pylori in tumor tissue of gastric advanced carcinomas and in adjacent non-tumor mucosa of operated stomachs. The presence of H. pylori was predominant in the intestinal-type carcinoma.
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Carcinoma/microbiología , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/aislamiento & purificación , Neoplasias Gástricas/microbiología , Estómago/microbiología , Adulto , Anciano , Colorantes Azulados , Biopsia , Carcinoma/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por Helicobacter/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estómago/patología , Neoplasias Gástricas/patología , Ureasa/análisisRESUMEN
PURPOSE: To investigate the role of beta-(1-3)-D-glucan on 99mTc labelled Escherichia coli translocation and cytokines secretion in rats submitted to small bowel ischemia/reperfusion injury. METHODS: Five groups (n=10 each) of Wistar rats were subjected to control(C), sham(S), group IR subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R), and group I/R+glucan subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R) and injected with 2 mg/Kg intramuscular. Translocation of labelled bacteria to mesenteric lymph nodes, liver, spleen, lung and serum was determined using radioactivity/count and colony forming units/g(CFU/g). Serum TNFalpha, IL-1beta, IL-6, IL-10 were measured by ELISA. RESULTS: CFU/g and radioactivity/count were higher in I/R than in I/R+glucan rats. In C, S and S+glucan groups, bacteria and radioactivity/count were rarely detected. The I/R+glucan rats had enhancement of IL-10 and suppressed production of serum TNFalpha, IL-1beta and, IL-6, compared to I/R untreated animals. CONCLUSION: The beta-(1-3)-D-glucan modulated the production of pro-inflammatory and anti-inflammatory cytokines during bowel ischemia/reperfusion, and attenuated translocation of labelled bacteria.
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Traslocación Bacteriana/efectos de los fármacos , Escherichia coli/fisiología , Intestino Delgado/irrigación sanguínea , Daño por Reperfusión/prevención & control , beta-Glucanos/farmacología , Animales , Traslocación Bacteriana/fisiología , Recuento de Colonia Microbiana , Citocinas/biosíntesis , Citocinas/metabolismo , Modelos Animales de Enfermedad , Mediadores de Inflamación/fisiología , Mucosa Intestinal/microbiología , Mucosa Intestinal/fisiología , Masculino , Proteoglicanos , Ratas , Ratas Wistar , Daño por Reperfusión/microbiología , Factor de Necrosis Tumoral alfa/sangreRESUMEN
PURPOSE: Statins are widely recognized as hypolipemic drugs, but some studies have observed anti-inflammatory and immunomodulatory effects, known as pleiotropic. The aims of this work was to study possible anti-inflammatory effects of simvastatin in abdominal sepsis. Serum pro-inflammatory cytokines and leukocytes count were determined in an experimental model of abdominal sepsis, using cecal ligation and puncture (CLP) in rats. METHODS: Twenty eight Wistar rats weighing 285+/-12 g were randomly divided in: CLP/Sinvastatin rats (n=7), treated with 10 mg/Kg of oral simvastatin 18 and 2 hs before CLP; CLP/Saline group rats (n=7), treated with oral saline; group Sham/Simvastatin (n=7), treated with simvastatin, and group Sham/Saline (n=7), treated with saline. Serum TNF-alpha, IL-1beta and IL-6 by ELISA and total leukocytes, neutrophils, lymphocytes, and eosinophils were determined 24 hs after CLP. ANOVA and Tukey test were used considering significant p<0.05. RESULTS: It was demonstrated that serum TNF-alpha, IL-1beta and IL-6 were respectively 364.8+/-42 pg/mL; 46.3+/-18 pg/mL and 28.4+/-13 pg/mL in CLP/Sinvastatin rats, significantly lower (p<0.05) than in group CLP/Saline (778.5+/-86 pg/ml; 176.9+/-46 pg/ml; 133.6+/-21 pg/ml, respectively). The same results were observed in total leukocytes and neutrophils counts. CONCLUSION: These results clearly demonstrate that simvastatin is an effective agent that reduces cytokines levels and leukocyte count in sepsis, independently of its well-known lipid-lowering effects. Thus, HMG-CoA reductase inhibitors like simvastatin have important anti-inflammatory effects in abdominal sepsis in rats.
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Antiinflamatorios/uso terapéutico , Citocinas/sangre , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Sepsis/tratamiento farmacológico , Simvastatina/uso terapéutico , Animales , Ciego/cirugía , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Leucocitos/efectos de los fármacos , Linfocitos/inmunología , Neutrófilos/inmunología , Distribución Aleatoria , Ratas , Ratas Wistar , Sepsis/inmunología , Factor de Necrosis Tumoral alfa/sangreRESUMEN
PURPOSE:: To evaluate the effects of modified coconut water as fluid of resuscitation combined with simvastatin in hemorrhagic shock and sepsis model in rats. METHODS:: Four groups of Wistar rats with hemorrhagic shock and abdominal sepsis were studied (n=8/group). Rats were bled and maintained at a mean blood pressure 35mmHg for 60min. They were then resuscitated with: 1) saline 0.9%; 2) coconut water+3% NaCl; 3) coconut water+NaCl 3%+simvastatin microemulsion (10 mg/kg i.v.; 4) normal coconut water. At 8h post-resuscitation, blood and lungs were collected for exams. RESULTS:: Clinical scores, TNF-α, IL-1ß, liver/kidney proof levels, and lung injury were significantly reduced in coconut water+NaCl 3%+simvastatin group treated rats, comparing with the other resuscitation treatments. CONCLUSIONS:: Resuscitation with coconut water with Nacl 3%+simvastatin had a significant beneficial effect on downregulating cytokines and decreasing lung injury in a rat model of abdominal sepsis and hemorrhagic shock. We also demonstrated that coconut water with Nacl 3%+simvastatin administration clearly made liver and kidney function better and improved clinical score.
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Cocos/química , Sepsis/tratamiento farmacológico , Choque Hemorrágico/tratamiento farmacológico , Simvastatina/administración & dosificación , Agua , Animales , Cacao , Modelos Animales de Enfermedad , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Pulmón/efectos de los fármacos , Ratas , Ratas Wistar , Resucitación/métodos , Cloruro de Sodio/administración & dosificaciónRESUMEN
PURPOSE: To investigate the antimicrobial, immunological and healing effects of Melipona scutellaris honey on infected wounds of rat skin. METHODS: Twenty four Wistar rats were distributed in four groups (6-each). The uninfected skin wounds of group I rats were treated daily with saline for 7 days. Uninfected wounds (group II) rats were treated with honey. In group III (treated with saline) and group IV (treated with honey) wounds were inoculated with MRSA ATTC43300. The first bacterial culture was performed 24 hours later. In the 7th day new culture was done, and wound biopsies were used for cytokines dosage and histopathology. RESULTS: In group I and III rats the CFU/g count of S. aureus in wounds was zero. In group II rats the CFU/g counts in the wound tissue were significantly higher than in wounds of group IV rats. The density histopathological parameters and the expression of TNF-α, IL1-ß, Il-6 were significantly higher on wounds of group IV then in the other groups. CONCLUSION: Honey of Melipona scutellaris was effective in the management of infected wounds, by significant bacterial growth inhibition, enhancement of cytokine expression, and positively influenced the wound repair.
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Apiterapia , Miel , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas/terapia , Cicatrización de Heridas , Animales , Carga Bacteriana , Colágeno/análisis , Fibroblastos , Interleucina-1beta/análisis , Interleucina-6/análisis , Leucocitos , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Modelos Animales , Distribución Aleatoria , Ratas Wistar , Infecciones Estafilocócicas/microbiología , Factor de Necrosis Tumoral alfa/análisis , Infección de Heridas/microbiología , Infección de Heridas/terapiaRESUMEN
PURPOSE: A comparison was done between the F. Paulino jejunal pouch (FP) and a jejunal pouch (JP) as esophagus-duodenum interpositional graft, for replacing the stomach after total gastrectomy. It was investigated the effect of the two procedures on esophagus histology, nutritional state and serum gastrin in rats. METHODS: Male Wistar rats weighing 282 +/- 17g were randomly submitted to sham operation (S), FP and JP after total gastrectomy. After eight weeks the rats were killed with overdose of anesthetic and tissue was taken from the distal esophagus for histology. Serum levels of total proteins, albumin, iron, transferring, folate, cobalamine, calcium, as well as serum gastrin were determined. Survival was considered. RESULTS: Fourty six rats were operated and thirty survived for eight weeks. Five (33.3%) died after FP and 11 (52.3%) after JP (p < 0.05). Postoperative esophagitis occurred in 6 JP rats. At 8th week, no difference was observed on body weight when compared FP and JP rats (p > 0.05). The JP rats had a significant decrease in serum albumin, glucose, transferrin, iron, folate and calcium, compared to sham (p < 0.05). Serum gastrin, iron and calcium were significantly higher in JP rats than in FP rats (p < 0.05). In FP rats, transferrin and cobalamine showed significant decrease comparing the preoperative with 8th week levels (p < 0.05). CONCLUSION: F. Paulino pouch in rats had lower mortality than JP, and esophagitis was not detected in it. JP rats had serum gastrin, iron and calcium unaffected, possibly because of preservation of duodenal passage.