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Water-insoluble glucan was isolated from the baker's yeast Saccharomyces cerevisiae. The yeast cells were treated with alkali and the residue then with acid. Chemical and NMR (1D and 2D) analyses showed that a linear (1â3)-ß-glucan was purified that was not contaminated with other carbohydrates, proteins or phenolic compounds. The effects of the glucan on wound healing were assessed in human venous ulcers by histopathological analysis after 30 days of topical treatment. (1â3)-ß-glucan enhanced ulcer healing and increased epithelial hyperplasia, as well as increased inflammatory cells, angiogenesis and fibroblast proliferation. In one patient who had an ulcer that would not heal for over 15 years, glucan treatment caused a 67.8% decrease in the area of the ulcer. This is the first study to investigate the effects of (1â3)-ß-glucan on venous ulcer healing in humans; our findings suggest that this glucan is a potential natural biological response modifier in wound healing.
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Polisacáridos Fúngicos/uso terapéutico , Glucanos/uso terapéutico , Úlcera Varicosa/tratamiento farmacológico , Adulto , Anciano , Femenino , Polisacáridos Fúngicos/aislamiento & purificación , Polisacáridos Fúngicos/farmacología , Glucanos/aislamiento & purificación , Glucanos/farmacología , Humanos , Masculino , Persona de Mediana Edad , Saccharomyces cerevisiae/química , Cicatrización de Heridas/efectos de los fármacosRESUMEN
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
Oral mucositis (OM) is one of the main side effects of the head and neck cancer treatment, particularly radiotherapy and/or chemotherapy. OM is characterized by ulcers, erythema, dysphagia, xerostomia, and increased susceptibility to opportunistic infections. In the perspective of finding pharmacological therapies to prevent inflammation and ulceration of OM, the investigation of the pleiotropic effect of commercial drugs is needed, among them gliclazide, an antidiabetic drug. This study aimed to evaluate the effect of gliclazide in an experimental OM model induced by 5-fluorouracil. Male hamsters were pre-treated with oral gliclazide (1, 5, or 10 mg/kg) for 10 days. Cheek pouch samples were subjected to histopathological and immunohistochemical analysis (COX2, iNOS, MMP-2, NFκB P65, GPx) and imunofluorescence (P-selectin). IL-1ß and TNF-α levels, Myeloperoxidase activity (MPO) and malondialdehyde (MDA) levels were investigated by ultraviolet-visible spectroscopy analysis. NFκB NLS P50 protein levels were analyzed by western blotting. The group treated with gliclazide at a dose of 10 mg/kg showed presence of erythema, no evidence of erosion, and absence of mucosal ulceration with a score of 1 (1-2) (p < 0.01). Histopathological data for the group treated with gliclazide 10 mg/kg showed re-epithelialization, discrete mononuclear inflammatory infiltrate and absence of hemorrhage, edema, ulcers and abscesses with a score of 1 (1-1) (p < 0.01). Treatment with gliclazide 10 mg/kg reduced MPO activity (p < 0.001), MDA levels (p < 0.001) and NFκB NLS P50 (p < 0.05) protein levels, resulting in low immunostaining to Cox-2, iNOS (p < 0.05), NFκB P65 (p < 0.05), and negative immunoreaction to MMP-2 (p < 0.001). However, it appeared that for Gpx1, the staining was restored in the GLI 10-FUT group compared with 5FUT/saline (p < 0.05). Immunofluorescence revealed decreased levels of P-selectin (p < 0.001) after treatment with gliclazide 10 mg/kg (p < 0.05). In summary, gliclazide accelerated mucosal recovery and reduced oxidative stress and inflammation in the 5-FU-induced OM in hamsters.
RESUMEN
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
The growth of the urban population raises concern about municipal public managers in the sense of providing emergency medical services (EMS) that are aligned with the needs of prehospital emergency medical care demanded by the population. The literature review aims at presenting the response time of emergency medical services in several parts of the world and discussing some factors that interfere in the result of this indicator such as GDP (Gross Domestic Product) percentage spent on health and life expectancy of countries. The study will also show that in some of the consulted articles, authors suggest to EMS recommendations for decreasing the response time using simulations, heuristics and metaheuristics. Response time is a basic indicator of emergency medical services, in such a way that researchers use the descriptive statistics to evaluate this parameter. Europe and the USA outstand in the publication of studies that present this information. Some articles use stochastic and mathematical methods to suggest models that simulate scenarios of response time reduction and suggest such proposals to the local EMS. Countries in which the response time was identified have a high index of human development and life expectancy between 74.7 and 83.7 years.
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Servicios Médicos de Urgencia/estadística & datos numéricos , Tiempo de Tratamiento/estadística & datos numéricos , Ambulancias/estadística & datos numéricos , Servicios Médicos de Urgencia/tendencias , Producto Interno Bruto , Humanos , Factores de Tiempo , Tiempo de Tratamiento/tendenciasRESUMEN
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
PURPOSE: This study explores the potential of the simvastatin to ameliorate inflammation and infection in open infected skin wounds of rats. METHODS: Fourteen Wistar rats weighing 285 +/- 12g were used. The study was done in a group whose open infected skin wounds were treated with topical application of simvastatin microemulsion (SIM, n=7) and a second group with wounds treated with saline 0.9 % (SAL, n=7). A bacteriological exam of the wounds fluid for gram positive and gram negative bacteria, the tecidual expression of TNFá and IL-1â by immunohistochemical technique, and histological analysis by HE stain were performed. RESULTS: The expression of TNFa could be clearly demonstrated in lower degree in skin wounds treated with simvastatin (668.6 +/- 74.7 ìm(2)) than in saline (2120.0 +/-327.1 ìm(2)). In comparison, wound tissue from SIM group displayed leukocyte infiltration significantly lower than that observed in SAL group (p<0.05). Culture results of the samples taken from wound fluid on fourth post treatment day revealed wound infection in only one rat of group simvastatin (SIM), where Proteus mirabilis, Escherichia coli and Enterobacter sp were isolated. In the rats whose wounds were treated with saline (SAL), polymicrobial infection with more than 100,000 CFU/g was detected in all the wounds. CONCLUSION: In addition to its antiinflammatory properties, the protective effects of simvastatin in infected open skin wounds is able to reduce infection and probably has antibacterial action. The potential to treat these wounds with statins to ameliorate inflammation and infection is promising.
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Antibacterianos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Simvastatina/uso terapéutico , Infección de la Herida Quirúrgica/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Análisis de Varianza , Animales , Antibacterianos/farmacología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inflamación/tratamiento farmacológico , Interleucina-1beta/metabolismo , Distribución Aleatoria , Ratas , Ratas Wistar , Simvastatina/farmacología , Infección de la Herida Quirúrgica/microbiología , Infección de la Herida Quirúrgica/patología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
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
Oral mucositis (OM) is an important side effect of cancer treatment, characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstrated efficacy in preventing this side effect, the aim of this study was to examine the effect of dexamethasone (DEX) on OM induced by 5-fluorouracil (5-FU) in hamsters by studying signaling pathways. OM was induced in hamsters by 5-FU followed by mechanical trauma (MT) on day 4. On day 10, the animals were euthanized. The experimental groups included saline, MT, 5-FU, and DEX (0.25, 0.5, or 1 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The oral mucosal samples were analyzed by enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction (qPCR). DEX (0.5 or 1 mg/kg) reduced inflammation and ulceration of the oral mucosa of hamsters. In addition, DEX (1 mg/kg) reduced the cytokine levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and macrophage migration inhibitory factor (MIF). DEX (1 mg/kg) also reduced the immunoexpression of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-2, transforming growth factor (TGF)-ß, MIF, Smad 2/3, Smad 2/3 phosphorylated and NFκB p65 in the jugal mucosa. Finally, DEX (1 mg/kg) increased interleukin-1 receptor-associated kinase 3 (IRAK-M), glucocorticoid-induced leucine zipper (GILZ), and mitogen-activated protein kinase (MKP1) gene expression and reduced NFκB p65 and serine threonine kinase (AKt) gene expression, relative to the 5-FU group. Thus, DEX improved OM induced by 5-FU in hamsters.
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Dexametasona/farmacología , Fluorouracilo/toxicidad , Estomatitis/prevención & control , Animales , Cricetinae , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Mesocricetus , FN-kappa B/metabolismo , Fosforilación , Proteínas Smad/metabolismo , Estomatitis/inducido químicamente , Estomatitis/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Intestinal ischemia/reperfusion (I/R) may induce bacterial translocation (BT). Glutamine (GLN)-enriched nutrition decreases BT. However, little is known about the effect of glucan (GL) in BT. This study investigated the combined effect of GL/GLN on BT, intestinal damage, and portal blood cytokines in animals under I/R. Four groups of 10 rats each were subjected to 60 min of intestinal ischemia and 120 min of reperfusion. The control group (group 1) received only rat food/water, group 2 received glutamine via gavage, group 3 received subcutaneuos soluble (1, 3)-d-glucan, and group 4 received GL + GLN. A sham group (group 5) served as a normal control. Bacterial cultures of ileum, mesenteric lymph nodes (MLN), liver and lung biopsies, histological changes of ileum, and serum cytokines variables were examined after I/R. Data were analyzed by analysis of variance (ANOVA) and the Newman-Keuls test. Results showed that GLN, GL, and GL/GLN significantly reduced BT to MLN, liver, and lung. BT was more attenuated after GL treatment than GLN (P < .05). Rats treated with both GL and GLN exhibited lower bacterial colony counts than the ones treated only with GLN or GL. Severe mucosal damage on histological findings was shown in group 1, but these findings were significantly ameliorated (P < .05) in groups 3 and 4. Tumor necrosis factor (TNF)-a and interleukin (IL)-6 levels in portal serum were significantly reduced and IL-10 was increased by GL and GLN treatment. In conclusion, the use of GL was more effective than GLN in reducing BT, intestinal damage, and cytokine levels after I/R. Additionally, the combination of GL and GLN improved results.
Asunto(s)
Glucanos/farmacología , Glutamina/farmacología , Íleon/irrigación sanguínea , Íleon/lesiones , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/microbiología , Animales , Citocinas/sangre , Enterobacteriaceae/aislamiento & purificación , Íleon/efectos de los fármacos , Íleon/microbiología , Masculino , Ratas , Ratas Wistar , Daño por Reperfusión/patologíaRESUMEN
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.
Asunto(s)
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.
Asunto(s)
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: Laparoscopic surgery is associated with reduced surgical trauma, and less acute phase response, as compared with open surgery. Cytokines are important regulators of the biological response to surgical and anesthetic stress. The aim of this study was to determine if CO2 pneumoperitoneum would change cytokine expression, gas parameters and leukocyte count in septic rats. METHODS: Wistar rats were randomly assigned to five groups: control (anesthesia only), laparotomy, CO2 pneumoperitoneum, cecum ligation and puncture by laparotomy, and laparoscopic cecum ligation and puncture. After 30 min of the procedures, arterial blood samples were obtained to determine leukocytes subpopulations by hemocytometer. TNFalpha, IL-1beta, IL-6 were determined in intraperitoneal fluid (by ELISA). Gas parameters were measured on arterial blood, intraperitoneal and subperitoneal exudates. RESULTS: Peritoneal TNFalpha, IL-1beta and IL-6 concentrations were lower in pneumoperitoneum rats than in all other groups (p<0.05). TNFalpha, IL-1beta and IL-6 expression was lower in the laparoscopic than in laparotomic sepsis (p<0.05). Rats from laparoscopic cecum ligation and puncture group developed significant hypercarbic acidosis in blood and subperitoneal fluid when compared to open procedure group. Total white blood cells and lymphocytes were significantly lower in laparoscopic cecum ligation and puncture rats than in the laparotomic (p<0.01). Nevertheless, the laparotomic cecum ligation rats had a significant increase in blood neutrophils and eosinophils when compared with controls (p<0.05). CONCLUSIONS: This study demonstrates that the CO2 pneumoperitoneum reduced the inflammatory response in an animal model of peritonitis with respect to intraperitoneal cytokines, white blood cell count and clinical correlates of sepsis. The pneumoperitoneum produced hypercarbic acidosis in septic animals.