In vivo assessment of intratumoral aspirin injection to treat hepatic tumors

AIM: To study the antineoplastic efficacy of 10% aspirin intralesional injection on VX2 hepatic tumors in a rabbit model. METHODS: Thirty-two male rabbits (age: 6-9 wk; body weight: 1700-2500 g) were inoculated with VX2 hepatic tumor cells (104 cells/rabbit) via supraumbilical median laparotomy. On day 4 post-implantation, when the tumors were about 1 cm in diameter, the rabbits were randomly divided into the following groups (n = 8 each group) to assess early (24 h) and late (7 d) antineoplastic effects of intratumoral injection of 10% bicarbonate aspirin solution (experimental groups) in comparison to intratumoral injection of physiological saline solution (control groups): group 1, 24 h control; group 2, 24 h experimental; group 3, 7 d control; group 4, 7 d experimental. The serum biochemistry profile (measurements of glycemia, alkaline phosphatase, gamma-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase) and body weight measurements were obtained for all animals at the following time points: D0, before tumor implant; D4, day of treatment; D5, day of sacrifice for groups 1 and 2; D11, day of sacrifice for groups 3 and 4. Gross assessments of the abdominal and thoracic cavities were carried out upon sacrifice. The resected liver tissues, including hepatic tumors, were qualitatively (general morphology, signs of necrosis) and quantitatively (tumor area) assessed by histopathological analysis. RESULTS: Gross examination showed no alterations, besides the left hepatic lobe tumors, had occurred in the thoracic and abdominal cavities of any animal at any time point evaluated. However, the features of the tumor foci were distinctive between the groups. Compared to the control groups, which showed normal unabated tumor progression, the aspirin-treated groups showed imprecise but limited tumor boundaries and a general red-white coloration (indicating hemorrhaging) at 24 h post-treatment, and development of yellow-white areas of a cicatricial aspect at 7 d after treatment. At all time points evaluated, all except one biochemical parameters tested within the reference range (P > 0.05); a significant increase was detected in the alkaline phosphatase level of the control group 3 on D11 (P < 0.05). At 24 h post-treatment, the aspirintreated groups showed extensive coagulation necrosis accompanied by a remarkable absence of viable tumor foci; at 7 d after treatment, the tumors had completely disappeared in these animals and fibrous necrotic nodules had developed. In contrast, throughout the study course, the tumors of the control groups remained unchanged, showing tumor nodules without necrosis at the time point corresponding to 24 h post-treatment and increased amounts of tumor nodules at the time point corresponding to 7 d post-treatment. Quantitative analysis of the remaining tumor area revealed that the aspirin-treated groups had significantly smaller tumor foci at 24 h post-treatment (8.5% ± 0.7%) andat 7 d after treatment (11.0% ± 4.2%), compared to those in the control groups (24 h: 98.5% ± 1.5% and 7 d: 94.0% ± 2.7%; both, P < 0.005). CONCLUSION: Intralesional injection of a 10% aspirin solution causes destruction of VX2 hepatic tumors in rabbits without evidence of relapse at 7 d after treatment administration. © 2013 Baishideng.

Effect of copaiba oil in hepatic damage induced by acetaminophen in rats

PURPOSE: To investigate the effects of copaiba oil on the hepatic damage induced by paracetamol. METHODS: Thirty six rats were distributed into six study groups (N=6): control group, that didn't receive the acetaminophen; Acetaminophen Group, that only received the acetaminophen; Prophylactic Copaiba Group 1, that received copaiba oil two hours before the acetaminophen; Prophylactic Copaiba Group 7, that received copaiba oil seven days, once by day, before the acetaminophen; Therapy Copaiba Group, that received the copaiba oil two hours afther the acetaminophen; and N-Acetyl-Cysteine Group, , that received the N-Acetyl-Cysteine two hours afther the acetaminophen. Euthanasia was performed after 24 hours. The serum levels of AST, ALT, alkaline phosphatase, GT, total bilirubin, direct bilirubin and indirect bilirubin and histological analisis were analized. RESULTS: The prophylactic copaiba group 7, therapy copaiba group and N-Acetyl-Cysteine Group showed amounts of AST and ALT similar to the control group; and the prophylactic copaiba group 1 showed similar levels to the acetaminophen group. There was no significant difference between the groups regarding the amount of alkaline phosphatase and GT (p>0.05). The therapy copaiba group showed the highest levels of bilirubin and was statistically different from the other groups (p<0.01) and this increased the costs of direct bilirubin. Regarding histopathology, the oil of copaiba administered prophylactic or therapeutic form for 7 days could decrease the amount of necrosis and inflammatory infiltrate. CONCLUSION: Copaiba oil administered prophylactically for seven days, and therapeutic could reduce liver damage caused by paracetamol similarly N-Acetyl-Cysteine, however, when treated with copaiba therapeutically showed increases in bilirubin, costs increasing fraction indirect.

Hepatic steatosis associated with microsporidiosis in teleost fishes from Marajó Island, Brazil

Um total de 40 exemplares do peixe teleósteo Gobioides grahamae Palmer & Wheeler, 1955 foram obtidos a partir do município de Salvaterra na Ilha de Marajó, no estado brasileiro do Pará. Os fígados foram removidos e processados para a microscopia de luz. De modo geral, 90% das amostras apresentavam algum grau de esteatose hepática, a qual foi invariavelmente associada com a presença de Microsporidium sp. O presente estudo confirma a ocorrência de esteatose em G. grahamae associada a infecções parasitárias por Microsporidium. Os resultados indicam que as condições de peixes saudáveis em ambiente natural podem ser afetadas negativamente por parasitas.

An anatomopathological study of hepatic coccidiosis (Calyptospora sp.) in the Acará-pixuna, Aequidens plagiozonatus Kullander, 1984 from the Brazilian state of Pará

Descreveram-se as alterações anatomopatológicas provocadas pelo parasitismo por Calyptospora sp. em 40 espécimes de Aequidens plagiozonatus, provenientes do município de Peixe-boi, Pará, Brasil. Foram encontradas formas imaturas e oocistos característicos do gênero Calyptospora, nos exames frescos por compressão e cortes histológicos, além de um grande número de centros melanomacrofágicos dispersos por todo o órgão. Digna de nota foi a ausência de inflamação significativa no tecido hepático. Centros melanomacrofágicos e compressão dos hepatócitos estão envolvidos na resposta do hospedeiro ao parasito. Este é o primeiro registro de ocorrência de parasitismo por Calyptospora sp. na espécie estudada.

Effect of concurrent training on risk factors and hepatic steatosis in obese adolescents

OBJETIVOAnalisar os efeitos de 20 semanas de treinamento concorrente sobre as variáveis de composição corporal, perfil lipídico e diagnóstico da esteatose hepática em adolescentes obesos.MÉTODOSRealizou-se um ensaio clínico aberto com 34 adolescentes obesos com idades entre 12 e 15 anos. Foram analisados gordura corporal total e de tronco, colesterol total e suas frações (HDL, LDL e VLDL) e triglicérides, sendo realizado exame de ultrassonografia de abdome superior para diagnosticar esteatose hepática. Os participantes foram submetidos ao treinamento concorrente (associação de treino com pesos e exercício aeróbio) três vezes por semana, com duração de uma hora-aula durante 20 semanas. Para o tratamento estatístico, foram realizados o teste t de Student pareado e a análise de frequência, a fim de verificar as reduções relativa e absoluta do diagnóstico da esteatose hepática, adotando-se p<0,05.RESULTADOSOs adolescentes estudados apresentaram melhoras significativas da composição corporal, com diminuição do percentual de gordura total, da massa gorda total, da gordura de tronco e do aumento da massa magra, além de redução do tamanho dos lóbulos do fígado, dos índices de prevalência da esteatose hepática, do colesterol total e LDL-colesterol.CONCLUSÕESO treinamento concorrente foi efetivo por promover melhorias significativas de variáveis da composição corporal e do perfil lipídico, além de reduzir a prevalência da esteatose hepática.

Evaluation of Renal Protection From High Doses of Melatonin in an Experimental Model of Renal Ischemia and Reperfusion in Hyperglycemic Rats

Background. Melatonin is a free radical scavenger with important actions in the study of renal ischemia and reperfusion (I/R). This study evaluated possible renal protection of high doses of melatonin in an experimental model of I/R in which rats were submitted to acute hyperglycemia under anesthesia with isoflurane.Method. Forty-four male Wistar rats, weighing more than 300 g, were randomly divided into 5 groups: G1, sham (n = 10); G2, melatonin (n = 10; 50 mg.kg(-1)); G3, hyperglycemia (n = 9; glucose 2.5 g.kg(-1)); G4, hyperglycemia/melatonin (n = 10; 2.5 g.kg(-1) glucose + melatonin 50 mg.kg(-1)); and G5, I/R (n = 5). In all groups, anesthesia was induced with 4% isoflurane and maintained with 1.5% to 2.0% isoflurane. Intraperitoneal injection of melatonin (G1, G4), glucose (G3, G4), or saline (G1, G5) was performed 40 minutes before left renal ischemia. Serum plasma values for creatinine and glucose were determined at baseline (M1), immediately following reperfusion (M2), and 24 hours after completion of the experiment (M3). Histological analysis was performed to evaluate tubular necrosis (0-5).Results. Serum glucose was higher at M2 in the groups supplemented with glucose, hyperglycemia (356.00 +/- 107.83), and hyperglycemia/melatonin (445.3 +/- 148.32). Creatinine values were higher at T3 (P = .0001) for I/R (3.6 +/- 0.37), hyperglycemia/melatonin (3.9 +/- 0.46), and hyperglycemia (3.71 +/- 0.69) and lower in the sham (0.79 +/- 0.16) and melatonin (2.01 +/- 1.01) groups, P < .05. Histology showed no necrosis injury in the G1, lesion grade 2 in the G2, and severe acute tubular necrosis in the G3: (grade 4), G4: (grade 5) and G5: (grade 4) groups (P < .0001).Discussion. Melatonin protected the kidneys submitted to I/R in rats without hyperglycemia; however, this did not occur when the I/R lesion was associated with hyperglycemia.Conclusions. Due to its antioxidant and antiapoptotic action, melatonin was able to mitigate, but not prevent acute tubular necrosis in rats with hyperglycemia under anesthesia by isoflurane.

Effects of Thermal Stress on Hepatic Melanomacrophages of Eupemphix nattereri (Anura)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exercise training decreases mitogen-activated protein kinase phosphatase-3 expression and suppresses hepatic gluconeogenesis in obese mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Embolization of splenorenal shunt associated to portal vein thrombosis and hepatic encephalopathy

Hepatic encephalopathy (HE) is a cognitive disturbance characterized by neuropsychiatric alterations. It occurs in acute and chronic hepatic disease and also in patients with portosystemic shunts. The presence of these portosystemic shunts allows the passage of nitrogenous substances from the intestines through systemic veins without liver depuration. Therefore, the embolization of these shunts has been performed to control HE manifestations, but the presence of portal vein thrombosis is considered a contraindication. In this presentation we show a cirrhotic patient with severe HE and portal vein thrombosis who was submitted to embolization of a large portosystemic shunt. Case report: a 57 years-old cirrhotic patient who had been hospitalized many times for persistent HE and hepatic coma, even without precipitant factors. She had a wide portosystemic shunt and also portal vein thrombosis. The abdominal angiography confirmed the splenorenal shunt and showed other shunts. The larger shunt was embolized through placement of microcoils, and the patient had no recurrence of overt HE. There was a little increase of esophageal and gastric varices, but no endoscopic treatment was needed. Since portosystemic shunts are frequent causes of recurrent HE in cirrhotic patients, portal vein thrombosis should be considered a relative contraindication to perform a shunt embolization. However, in particular cases with many shunts and severe HE, we found that one of these shunts can be safely embolized and this procedure can be sufficient to obtain a good HE recovery. In conclusion, we reported a case of persistent HE due to a wide portosystemic shunt associated with portal vein thrombosis. As the patient had other shunts, she was successfully treated by embolization of the larger shunt. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Effect of protective solutions and hydroxyethyl starch in the attenuation of the injuries of ischemia and reperfusion of splanchnic organs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Parecoxib reduces renal injury in an ischemia/reperfusion model in rats

To evaluate the effect of parecoxib (an NSAID) on renal function by measuring plasma NGAL (serum neutrophil gelatinase-associated lipocalin) levels in an induced-ischemia rat model. METHODS: Forty male Wistar rats were randomly assigned to one of four groups: Ischemia (I), Ischemia/parecoxib (IP), No-ischemia (NI), and No-ischemia/parecoxib (NIP). Body weight, mean arterial pressure, heart rate, body temperature, NGAL levels, and renal histology were compared across groups. RESULTS: The Ischemia (I) group, which did not receive parecoxib, showed the highest NGAL levels (p=0.001), while the IP group, which received the medication, had NGAL levels similar to those of the non-ischemic (NI and NIP) groups. CONCLUSION: Parecoxib resulted in renal protection in this experimental model.

Dexmedetomidine on renal ischemia-reperfusion injury in rats: assessment by means of NGAL and histology

Background: Ischemic acute kidney injury is a common occurrence in the perioperative period and in critical patients admitted to intensive care units. The reestablishment of blood supply may worsen injury through the ischemia-reperfusion (I/R) mechanism. We investigated the effect of dexmedetomidine on the kidneys of rats subjected to an experimental I/R model. Methods: 34 rats anesthetized with isoflurane was undergone right nephrectomy and randomly assigned to four groups: Control C (saline solution); Dexmedetomidine D (dexmedetomidine); Sham S (saline solution); Sham with Dexmedetomidine SD (dexmedetomidine). The serum levels of neutrophil gelatinase-associated lipocalin (NGAL) were measured at time-points T1 (following stabilization), T2 (ischemia), T3 (reperfusion), T4 (12 h after of I/R). The kidneys were subjected to histological examination. Results: The NGAL levels were significantly higher at T4 compared with T1. Upon histological examination, the left kidneys in groups C and D exhibited a similar extent of cell injury. Conclusion: The levels of NGAL did not indicate either protection against or worsening of kidney injury. Histological examination for acute tubular necrosis showed that dexmedetomidine did not protect the kidneys from I/R.