Diagnostic accuracy of 18F-FDG-PET in abdominal sepsis in rats

Abstract 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.

Effect of Arrabidaea chica extract against chemically induced breast cancer in animal model

Abstract 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.

Wound healing of diabetic rats treated with Moringa oleifera extract

Abstract 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-1β 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.

Efeitos da sinvastatina na mucosite gastrointestinal induzida por 5-fluorouracil em ratos / Effects of simvastatin on 5-fluorouracil-induced gastrointestinal mucositis in rats

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

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

Drain amylase on the first postoperative day of whipple surgery: what value is the best predictor for early drain removal? / Amilase do dreno no primeiro dia de pós-operatório de operaçao de whipple: qual valor é melhor preditor para a retirada precoce do dreno?

ABSTRACT 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.

RESUMO Racional: O valor da amilase do dreno no primeiro dia pós-operatório após ressecções pancreáticas é descrito como eficiente preditor de fístula pancreática. Entretanto, o valor abaixo do qual os drenos podem ser removidos precocemente permanece controverso. Objetivo: Validar o uso da amilase do primeiro dia pós-operatório na correlação com a fístula pancreática e definir o valor em que seja segura a retirada precoce do dreno. Método: Foram incluídos pacientes submetidos à operação de Whipple no período de 2007 a 2016. No grupo 1 entraram os que não desenvolveram fístula e os que desenvolveram fístula bioquímica por menos de sete dias de pós-operatório e no grupo 2 os que desenvolveram fístula bioquímica persistente entre 7 e 21 dias e aqueles com fístula grau B e C. Resultados: Sessenta e um pacientes foram incluídos, sendo 41 do grupo 1 e 20 do grupo 2. A incidência de coleções abdominais, necessidade de reoperação e tempo de internação foram para o grupo 1 e 2, respectivamente 17,1%, 17,1% e 9,5 dias, e 65%, 40% e 21,1 dias. A mediana da amilase no grupo 1 e 2, respectivamente foi de 175 U/l e 3172,5 U/l (p=0,001). Utilizando o ponto de corte de 180 para predizer o grupo a que o paciente pertenceria, obteve-se sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo de: 100%, 48,8%, 50% e 100% respectivamente. Conclusão: Esta amostra pôde validar o ponto de corte de 180 U/l como adequado para a retirada precoce do dreno.

Influence of the colon in liver regeneration of rats submitted to hepatectomy and colectomy / Influência do cólon na regeneração do fígado de ratos submetidos à hepatectomia e colectomia

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

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

Anatomo-radiological correlation using 18-FDG-PET in abdominal sepsis model in rats. A preliminary study

Abstract 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.

The renoprotective effect of oral Tadalafil pretreatment on ischemia/reperfusion injury in rats

Abstract 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-1β (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.

Oxacillin magnetically targeted for the treatment of Methicillin-Resistant S. aureus infection in rats

Abstract 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.

Effects of cococonut water and simvastatin in the treatment of sepsis and hemorrhagic shock in rats

ABSTRACT 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-1β, 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.

Antibacterial properties and healing effects of Melipona scutellaris honey in MRSA-infected wounds of rats

ABSTRACT 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-β, 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.

Heart and systemic effects of statin pretreatment in a rat model of abdominal sepsis. Assessment by Tc99m-sestamibi biodistribition

PURPOSE: To evaluate the heart and the Tc-99m-sestamibi biodistribution after statin pretreatment in a rat model of abdominal sepsis. METHODS: Twenty-four Wistar rats were randomly distributed into four groups (n=6 per group): 1) sepsis with simvastatin treatment, 2) sepsis with vehicle, 3) sham control with simvastatin and 4) sham control with vehicle. 24 hours after cecal ligation and puncture rats received 1.0MBq of Tc-99m-sestamibi i.v. 30min after, animals were euthanized for ex-vivo tissue counting and myocardium histological analysis. RESULTS: Myocardial histologic alterations were not detected 24 hours post-sepsis. There was significantly increased cardiac Tc-99m-sestamibi activity in the sepsis group with simvastatin treatment (1.9±0.3%ID/g, p<0.001) in comparison to the sepsis group+vehicle (1.0±0.2%ID/g), control sham group+ simvastatin (1.2±0.3%ID/g) and control sham group (1.3±0.2%ID/g). Significant Tc-99m-sestamibi activity in liver, kidney and lungs was also detected in the sepsis group treated with simvastatinin comparison to the other groups. CONCLUSIONS: Statin treatment altered the biodistribution of Tc-99m-sestamibi with increased cardiac and solid organ activity in rats with abdominal sepsis, while no impact on controls. Increased myocardial tracer activity may be a result of a possible protection effect due to increased tissue perfusion mediated by statins. .

The ileum positively regulates hepatic regeneration in rats

To test the hypothesis that liver regeneration after partial hepatectomy can be influenced by the ileum. METHODS: Eighteen Wistar rats were distributed into groups of six animals: 1 - ileum resection+ hepatectomy 2/3; 2 - hepatectomy 2/3, and 3 - sham. Anesthesia with ketamine and xylazine i.p., aseptic technique, analgesia with meperidine (10mg/kg s.c.). On day 6, serum ALT, AST, alkaline phosphatase (AP) and albumin were measured. Liver regeneration and hepatocyte mitosis were quantified. Statistical analysis with ANOVA and Tukey tests, with significance p<0.05. RESULTS: In group hepatectomy+ileal resection, ALT, AST and AP were 180.6±24.9, 58.6±3.1 and 254.6±46.6 respectively. They were significantly higher than in the hepatectomy group, whose values were 126.0±16.5, 44.1±3.9 and 163.5±8.6, respectively (p<0.001). Albumin levels were not significantly different among groups. Liver regeneration in hepatectomy group (94.17%) was statistically higher (p<0.001) than in ileal resection+hepatectomy group (55.96%). In the latter group the mitosis of hepatocytes were significantly less frequent than in the hepatectomy group. CONCLUSION: The data confirm that the ileum positively influence on liver regeneration in rats undergoing hepatectomy.

Metabolic and hematologic consequences of colectomy associated to hepatectomy in rats / Consequências metabólicas e hematológicas da colectomia associada à hepatectomia em ratos

PURPOSE: To investigate the influence of partial colectomy associated with hepatectomy on the biodistribution of the 99mTc-phytate, on metabolic parameters, as well as labeling and morphology of red blood cells. METHODS: Wistar rats were distributed into three groups (each with six), nominated as colectomy, colectomy+hepatectomy and sham. In the 30th postoperative day all rats were injected with 99mTc-phytate 0.1mL i.v. (radioactivity 0.66 MBq). After 15 minutes, liver sample was harvested and weighed. Percentage radioactivity per gram of tissue ( percentATI/g) was determined using an automatic gamma-counter. Serum AST, ALT, alkaline phosphatase and red blood cells labeling were determined. RESULTS: The liver percentATI/g and red blood cells labeling were lower in colectomy and colectomy+hepatectomy rats than in sham rats (p <0.05), and no difference was detected comparing the colectomy and colectomy+hepatectomy groups. Red blood cells morphology did not differ among groups. Serum levels of AST, ALT and alkaline fosfatase were significantly higher in colectomy+hepatectomy than in colectomy rats (p<0.001). CONCLUSION: Hepatectomy associated with colectomy lowered the uptake of radiopharmaceutical in liver and in red blood cells in rats, coinciding with changes in liver enzymatic activity.

OBJETIVO: Investigar a influência da colectomia associada à hepatectomia parcial, na biodistribuição do fitato-99mTcO4, na marcação e morfologia de hemácias e em parâmetros metabólicos. MÉTODOS: Ratos Wistar foram distribuídos em três grupos (seis animais cada), denominados: colectomia, colectomia+hepatectomia e sham. No 30º dia pós-operatório, em todos eles foi feita injeção de 0,1 mL i.v. de fitato-99mTcO4 (radioatividade 0,66 MBq). Após 15 minutos, uma amostra de fígado foi colhida e pesada. O percentual de radioatividade por grama de tecido ( por centoATI/g) foi determinado no fígado e hemácias usando-se um contador gama automático. Dosagem sérica de AST, ALT, fosfatase alcalina, morfologia e marcação de hemácias com pertecnetato foram determinadas. RESULTADOS: O por centoATI/g no fígado e nas hemácias foi menor nos animais dos grupos colectomia e colectomia+hepatectomia do que no grupo sham (p<0,05; teste de Tukey). Nenhuma diferença foi detectada comparando os grupos colectomia e colectomia+hepatectomia. A morfologia das hemácias não diferiu entre os três grupos. Os níveis séricos de AST, ALT e fosfatase alcalina foram significativamente maiores no grupo colectomia+hepatectomia do que no grupo colectomia (p<0,001). CONCLUSÃO: A colectomia associada a hepatectomia contribuiu para reduzir a captação de radiofármaco no fígado e hemácias de ratos, coincidindo com alterações na atividade enzimática do fígado.

Effect of sildenafil in renal ischemia/reperfusion injury in rats / Efeito do sildenafil na lesão renal por isquemia/reperfusão em ratos

PURPOSE: To evaluate the effect of sildenafil, administered prior to renal ischemia/reperfusion (I/R), by scintigraphy and histopathological evaluation in rats. METHODS: Twenty-four rats were divided randomly into two groups. They received 0.1 ml of 99mTechnetium-etilenodicisteine intravenous, and a baseline (initial) renal scintigraphy was performed. The rats underwent 60 minutes of ischemia by left renal artery clamping. The right kidney was not manipulated. The sildenafil group (n=12) received orally 1 mg/kg of sildenafil suspension 60 minutes before ischemia. Treatment with saline 0.9 percent in the control group (n=12). Half of the rats was assessed after 24 hours and half after seven days I/R, with new renal scintigraphy to study differential function. After euthanasia, kidneys were removed and subjected to histopathological examination. For statistical evaluation, Student t and Mann-Whitney tests were used. RESULTS: In the control group rats, the left kidneys had significant functional deficit, seven days after I/R, whose scintigraphic pattern was consistent with acute tubular necrosis, compared with the initial scintigraphy (p<0.05). Sildenafil treatment resulted in better differential function of the left kidneys 24h after reperfusion, compared with controls. Histopathologically, the left kidney of control rats (24 hours after I/R) showed a higher degree of cellular necrosis when compared with the sildenafil treated rats (p<0.05). CONCLUSION: Sildenafil had a protective effect in rat kidneys subjected to normothermic I/R, demonstrated by scintigraphy and histomorphometry.

OBJETIVO: Estudar o efeito do sildenafil, administrado previamente à isquemia/reperfusão (I/R) renal, em avaliações cintilográficas e histopatológicas em ratos. MÉTODOS: Vinte e quatro ratos Wistar foram aleatoriamente distribuídos em dois grupos. Os animais receberam 0,1 ml IV de 99mTecnécio-Etilenodicisteína, foram submetidos à cintilografia renal inicial e em seguida submetidos a isquemia no rim esquerdo, com oclusão da artéria renal, durante 60 minutos, com posterior reperfusão. O grupo sildenafil (n=12) recebeu previamente 1mg/kg de sildenafil em suspensão 60 minutos antes da isquemia. Solução salina 0,9 por cento foi administrada no grupo controle (n=12). Metade dos animais de cada grupo foi avaliada após 24 horas e a outra metade após sete dias de reperfusão, com nova cintilografia renal. Após eutanásia, os rins foram retirados e submetidos a exame histopatológico. Na avaliação estatística foram empregados os testes t de Student e de Mann-Whitney. RESULTADOS: Foi observado no rim esquerdo (submetido a I/R) do grupo controle déficit funcional diferencial nas imagens cintilográficas após sete dias, com padrão de necrose tubular aguda, quando comparado com a cintilografia inicial (p<0,05). O tratamento com sildenafil resultou em melhor função diferencial do rim esquerdo 24h após reperfusão, comparado com os controles. Na histopatologia, os rins esquerdos dos animais do grupo controle (24 horas pós-I/R), apresentaram maior grau de necrose celular quando comparados com o grupo tratado com o sildenafil (p<0,05). CONCLUSÃO: O sildenafil teve efeito protetor em rins de ratos submetidos à isquemia/reperfusão normotérmica, demonstrado por cintilografia e histomorfometria.

Biodistribution of technetium-99m pertechnetate after Roux-en-Y gastric bypass (Capella technique) in rats / Biodistribuição de tecnécio-99m pertecnetato após desvio gástrico em Y de Roux (técnica de Capella) em ratos

PURPOSE: The biodistribution of sodium pertechnetate, the most used radiopharmaceutical in nuclear medicine, has not been studied in details after bariatric surgery. The objective was to investigate the effect of Roux-en-Y gastric bypass (RYGB) on biodistribution of sodium pertechnetate (Na99mTc-) in organs and tissues of rats. METHODS: Twelve rats were randomly divided into two groups of 6 animals each. The RYGB group rats were submitted to the Roux-en-Y gastric bypass and the control group rats were not operated. After 15 days, all rats were injected with 0.1mL of Na99mTc- via orbital plexus with average radioactivity of 0.66 MBq. After 30 minutes, liver, stomach, thyroid, heart, lung, kidney and femur samples were harvested, weighed and percentage of radioactivity per gram ( percentATI/g) of each organ was determined by gama counter Wizard Perkin-Elmer. We applied the Student t test for statistical analysis, considering p<0.05 as significant. RESULTS: Significant reduction in mean percentATI/g was observed in the liver, stomach and femur in the RYGB group animals, compared with the control group rats (p<0.05). In other organs no significant difference in percentATI/g was observed between the two groups. CONCLUSION: This work contributes to the knowledge that the bariatric surgery RYGB modifies the pattern of biodistribution of Na99mTc-.

OBJETIVO: Avaliar o efeito da cirurgia de desvio gástrico em Y de Roux (BGYR) na biodistribuição do pertecnetato de sódio (Na99mTc) em órgãos e tecidos de ratos. MÉTODOS: Doze ratos Wistar foram aleatoriamente distribuidos em dois grupos de seis animais cada. O grupo BGYR foi submetido a técnica cirúrgica do desvio gástrico em Y de Roux e o grupo controle não foi operado. No 15º dia de pós-operatório foi administrado 0,1 ml IV de Na99mTc aos animais dos dois grupos, com atividade radioativa média de 0,66MBq. Após 30 minutos os ratos foram mortos e retirados fragmentos de fígado, estômago, tireóide, coração, pulmão, rim e fêmur. As amostras foram lavadas com solução salina 0,9 por cento pesadas e submetidas ao Contador Gama 1470, WizardTM Perkin-Elmer para se determinar o percentual de atividade radiotiva por grama ( por centoATI/g) de cada órgão. Empregou-se o teste t de Student para análise estatística, considerando p<0,05 como significante. RESULTADOS: Redução significante na média de por centoATI/g foi observada no fígado, estômago e fêmur nos animais submetidos a cirurgia de BGYR comparado com o grupo controle (p<0,05). Nos demais órgãos não houve diferença significante no por centoATI/g entre os dois grupos. CONCLUSÃO: A cirurgia BGYR em ratos modificou a biodistribuição do Na99mTc em alguns órgãos, podendo ter implicações clínicas na interpretação de exames cintilográficos.

Protective effect of simvastatin in the cyclophosphamide-induced hemohrragic cystitis in rats / Efeito protetor da sinvastatina na cistite hemorrágica induzida pela ciclofosfamida em ratos

PURPOSE: Cyclophosphamide (CYP) is an antineoplastic agent used for the treatment of many neoplastic and inflammatory diseases. Hemorrhagic cystitis is a frequent side effect of CYP. Several studies show that simvastatin has important pleiotropic (anti-inflammatory and immunomodulatory) effects. The purpose of the study was to investigate the effect of simvastatin on bladder, ureter and kidney injury caused by CYP. METHODS: Adult male Wistar rats were randomly divided into three groups. The CYP/SIM group received simvastatin microemulsion by gavage during 7 days (10 mg/kg body wt) before the administration of CYP and the CYP/SAL group rats received saline 0.9 percent. The control rats were not treated. After that, all rats were treated with a single dose of CYP 200 mg/kg body wt intraperitoneally. The rats were killed 24 h after CYP administration. Plasma cytokines (TNF-α, IL-1β, IL-6) were measured by ELISA. Macro and light microscopic study was performed in the bladder, kidney and ureter. RESULTS: In the bladders of CYP/SIMV treated rats edema of lamina propria with epithelial and sub-epithelial hemorrhage were lower than in CYP/SAL treated rats. The scores for macroscopic and microscopic evaluation of bladder and ureter were significantly lower in CYP/SIMV rats than in CYP/SAL rats. The kidney was not affected. The expression of TNF-α, IL-1β and IL-6 was significatly lower in CF/SINV rats (164.8±22, 44.8±8 and 52.4±13) than in CF/SAL rats (378.5±66, 122.9±26 e 123.6±18), respectively. CONCLUSION: The results of the current study suggest that simvastatin pretreatment attenuated CYP-induced urotelium inflammation and decreased the activities of cytokines.

OBJETIVO: Ciclofosfamida (CF) é um agente antineoplásico frequente implicado na etiologia da cistite hemorrágica. Vários estudos mostram que a sinvastatina tem importantes efeitos pleiotrópicos (anti-inflamatórios e imunomoduladores). O objetivo do trabalho foi estudar os efeitos da sinvastatina na prevenção de cistite hemorrágica e lesões uroteliais induzidas por CF em modelo experimental. MÉTODOS: Doze ratos Wistar foram distribuídos de forma randomizada em três grupos: nos ratos do grupo experimental (CF/SINV), foi administrada microemulsão de sinvastatina 10mg/Kg, por via oral (gavagem), durante 7 dias antes da administração de CF e os ratos do grupo controle (CF/SAL), foram tratados com solução salina 0,9 por cento nas mesmas doses e prazos. O grupo controle não foi tratado. Todos os ratos foram tratados com CF 200mg/Kg intraperitonial (dose única) e 24 horas após foram sacrificados. Exame macro e microscópico foi feito na bexiga e os rins e ureteres foram avaliados microscopia. Foram realizadas dosagens plasmáticas de TNF-α, IL-1β, IL-6 (ELISA). RESULTADOS: O escore para avaliação macroscópica do dano à bexiga e o escore para avaliação do dano histológico na bexiga e nos ureteres mostraram-se significativamente menores no grupo CF/SINV em comparação ao grupo CF/SAL (p<0,05). Os rins não foram afetados. A expressão de TNF-α, IL-1β, IL-6 também foi significativamente menor (p<0,05) no grupo CF/SINV (164,8±22, 44,8±8 e 52,4±13) em comparação ao grupo CF/SAL (378,5±66, 122,9±26 e 123,6±18), respectivamente. CONCLUSÃO: O estudo demonstrou eficácia da sinvastatina na atenuação da cistite hemorrágica e lesão ureteral induzidas por CF em ratos Wistar, através da interferência nas citocinas plasmáticas e nas lesões uroteliais.

Efeito da sinvastatina na sepse abdominal de ratos diabéticos / Effect of the simvastatin in abdominal sepsis of diabetic rats

OBJETIVO: Analisar se o pré-tratamento com sinvastatina em modelo experimental de sepse abdominal é benéfico em ratos diabéticos. MÉTODOS: Cinquenta e seis ratos Wistar foram aleatoriamente distribuídos em: grupo não diabético (n-28) e grupo diabetes induzido por estreptozotocina (n=28). Sepse abdominal por ligadura e punção do ceco foi induzida em 14 ratos diabéticos e em 14 não diabéticos. Os demais 28 animais foram alocados em grupo sham. Os grupos de ratos com sepse e os sham (cada com sete animais) foram tratados com microemulsão oral de simvastatina (20 mg kg-1 day-1) e solução salina 0,9 por cento, respectivamente. Sangue periférico foi usado para dosagem de TNFα, IL-1β, IL-6, proteína C reativa, procalcitonina, contagem de leucócitos e neutrófilos em todos os animais. A análise estatística foi realizada pela ANOVA e teste de Tukey, com p<0,05. RESULTADOS: A sinvastatina reduziu a mortalidade nos ratos diabéticos. Os valores séricos de TNF-α, IL-1β, IL-6, proteína C reativa, procalcitonina, leucócitos e neutrófilos mostraram-se mais baixos nos ratos diabéticos e não diabéticos com sepse, tratados com sinvastatina, do que nos tratados com solução salina. CONCLUSÃO: A sinvastatina teve efeito antiinflamatório, que pode ter resultado em proteção contra a sepse em ratos diabéticos.

OBJECTIVE: Infection and sepsis are major causes of morbidity and mortality after surgery of diabetic patients. Statins have been shown to exhibit anti-inflammatory and immunomodulatory (pleiotropic) effects, independent of lipid lowering. This study aimed to observe whether the pretreatment with simvastatin in a cecal ligation and perforation model of sepsis is beneficial in diabetic rats. METHODS: Fifty six Wistar rats were randomly assigned to non-diabetic group (n=28), and streptozotocin-induced diabetic group (n=28). Abdominal sepsis was induced in 14 diabetic and in 14 non diabetic rats and the other 28 rats were allocated on sham group. Sepsis rats and sham rats (each with 7 animals) were treated with oral simvastatin (20 mg kg-1 day-1) or normal saline solution 0.9 percent. Peripheral blood TNFα, IL-1β, IL-6, C-reactive protein, procalcitonin, leukocytes and neutrophils were tested in all the animals. Statistical analysis was done by ANOVA and Tukey test, with p<0.05. RESULTS: Simvastatin reduced mortality in diabetic rats. Peripheral blood TNFα, IL-1β, IL-6, C-reactive protein, procalcitonin, leukocytes and neutrophils were lower in diabetic and non diabetics septic rats treated with simvastatin, than after saline treatment. CONCLUSION: Simvastatin showed anti-inflammatory effect, which could play some protection against the progress of sepsis in diabetic rats.

Compensatory sweating after thoracoscopic sympathectomy: characteristics, prevalence and influence on patient satisfaction / Hiperhidrose compensatória após simpatectomia toracoscópica: características, prevalência e influência na satisfação do paciente

OBJECTIVE: This prospective study aimed at investigating predictive factors for compensatory sweating after thoracoscopic sympathectomy. METHODS: From 2000 to 2002, 80 patients (53 females and 27 males) underwent thoracoscopic sympathectomy to treat hyperhidrosis. Patient ages ranged from 12 to 56 years, and the mean post-operative follow-up period was 42.51 ± 5.98 months. Patient satisfaction with the results was evaluated through the use of a rating scale. The procedure was performed bilaterally: at the T2 level for facial hyperhidrosis; at the T3-T4 level for axillary hyperhidrosis; and at the T3 level for palmar hyperhidrosis. RESULTS: Post-operatively, 68 patients (85.0 percent) presented compensatory sweating, which was classified as mild in 23 (33.8 percent), moderate in 23 (33.8 percent) and severe in 22 (32.4 percent). Considering the final surgical results, 70 patients (87.5 percent) were satisfied with the outcome of the operation, whereas 10 patients (12.5 percent) were dissatisfied. The level of patient satisfaction varied according to gender, age, body mass index (BMI) and extent of denervation. The compensatory sweating was more severe on the abdomen and back than on the legs. CONCLUSIONS: Although compensatory sweating, which is a common adverse effect of sympathectomy, occurred in the majority of cases, the level of patient satisfaction was high. The best candidates for thoracoscopic sympathectomy are young adult women with a BMI < 24.9 kg/m².

OBJETIVO: Este estudo prospectivo visou investigar fatores preditivos para a hiperidrose compensatória após a simpatectomia toracoscópica. MÉTODOS: De 2000 a 2002, 80 pacientes (53 mulheres e 27 homens), com idade entre 12 e 56 anos, foram submetidos à simpatectomia toracoscópica para o tratamento de hiperidrose e acompanhados em média por 42,51 ± 5,98 meses. A satisfação destes pacientes quanto aos resultados do procedimento foi aferida por meio de uma escala de avaliação. O procedimento foi executado bilateralmente: no nível de T2 para a hiperidrose facial; de T3 e T4 para a hiperidrose axilar; e de T3 para a hiperidrose palmar. RESULTADOS: No período pós-operatório, 68 pacientes (85,0 por cento) apresentaram hiperidrose compensatória, que foi classificada como leve em 23 (33,85 por cento), moderada em 23 (33,8 por cento) e grave em 22 (32,4 por cento). Quanto aos resultados da cirurgia, na avaliação dos pacientes, 70 deles (87,5 por cento) se consideraram satisfeitos, enquanto 10 pacientes (12,5 por cento) disseram estar insatisfeitos. O grau de satisfação do paciente variou de acordo com o sexo, a idade, o índice de massa corpórea (IMC) e a extensão da operação. A hiperidrose compensatória foi mais intensa no abdome e dorso do que nas pernas. CONCLUSÕES: Embora a hiperidrose compensatória seja um efeito adverso frequente após a simpatectomia, o grau de satisfação dos pacientes foi elevado. Os melhores candidatos para simpatectomia toracoscópica são mulheres adultas jovens com IMC < 24,9 kg/m².

Biodistribution of samarium-153-EDTMP in rats treated with docetaxel / Biodistribuição de EDTMP-153-samário em ratos tratados com docetaxel

PURPOSE: Many patients with metastatic bone disease have to use radiopharmaceuticals associated with chemotherapy to relieve bone pain. The aim of this study was to assess the influence of docetaxel on the biodistribution of samarium-153-EDTMP in bones and other organs of rats. METHODS: Wistar male rats were randomly allocated into 2 groups of 6 rats each. The DS (docetaxel/samarium) group received docetaxel (15 mg/kg) intraperitoneally in two cycles 11 days apart. The S (samarium/control) group rats were not treated with docetaxel. Nine days after chemotherapy, all the rats were injected with 0.1ml of samarium-153-EDTMP via orbital plexus (25µCi). After 2 hours, the animals were killed and samples of the brain, thyroid, lung, heart, stomach, colon, liver, kidney and both femurs were removed. The percentage radioactivity of each sample ( percent ATI/g) was determined in an automatic gamma-counter (Wizard-1470, Perkin-Elmer, Finland). RESULTS: On the 9th day after the administration of the 2nd chemotherapy cycle, the rats had a significant weight loss (314.50±22.09g) compared (p<0.5) to pre-treatment weight (353.66± 22.8). The percent ATI/g in the samples of rats treated with samarium-153-EDTMP had a significant reduction in the right femur, left femur, kidney, liver and lungs of animals treated with docetaxel, compared to the control rats. CONCLUSION: The combination of docetaxel and samarium-153-EDTMP was associated with a lower response rate in the biodistribution of the radiopharmaceutical to targeted tissues. Further investigation into the impact of docetaxel on biodistribution of samarium-153-EDTMP would complement the findings of this study.

OBJETIVO: Muitos pacientes com metástases ósseas são tratados com radiofármacos associados com quimioterapia para alívio da dor óssea. O objetivo do trabalho foi estudar a influência do docetaxel na biodistribuição do EDTMP-153-samário nos ossos e outros órgãos de ratos. MÉTODOS: Ratos Wistar foram aleatoriamente alocados em 2 grupos de 6 animais cada. O grupo DS (docetaxel/samário) recebeu docetaxel (15 mg/kg) intraperitoneal em dois ciclos com 11 dias de intervalo. Os ratos do grupo S (samário/controle) não foram tratados com docetaxel. Nove dias após a quimioterapia, todos os animais receberam 0,1ml de EDTMP-153-samário via plexo orbital (25µCi). Após 2 horas, os animais foram mortos e feitas biópsias de cérebro, tireóide, pulmão, coração, estômago, cólon, fígado, rim e fêmures. O percentual de radioatividade por grama ( por centoATI/g) de tecido de cada biópsia foi determinado em contador gama automático (Wizard-1470, Perkin-Elmer, Finland). RESULTADOS: No 9º após 2º ciclo de docetaxel os ratos tiveram perda de peso significante, passando de 353,66± 22,8g (controle/pré-tratamento) para 314,50±22,09g (p<0,5). Os por cento ATI/g nos órgãos dos ratos tratados com EDTMP-153-samário e docataxel tiveram redução significante nos fêmures direito e esquerdo, rim, fígado e pulmão, quando comparados com os não tratados com docetaxel. CONCLUSÃO: A combinação de docetaxel com EDTMP-153-samário foi associada com resposta mais baixa na biodistribuição do radiofármaco em órgãos alvo. Futuras investigações sobre o impacto do docetaxel na biodistribuição do EDTMP-153-samário poderão complementar os achados teste estudo.