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1.
Surgery ; 169(6): 1512-1518, 2021 06.
Article in English | MEDLINE | ID: mdl-33678500

ABSTRACT

BACKGROUND: Liver ischemia reperfusion injury is still an unsolved problem in liver surgery and transplantation. In this setting, hypothermia is the gold standard method for liver preservation for transplantation. Hypertonic saline solution reduces inflammatory response with better hemodynamic recovery in several situations involving ischemia reperfusion injury. Here, we investigated the effect of hypertonic saline solution in hypothermic liver submitted to ischemia reperfusion injury. METHODS: Fifty male rats were divided into 5 groups: SHAM, WI (animals submitted to 40 minutes of partial warm liver ischemia and reperfusion), HI (animals submitted to 40 minutes hypothermic ischemia), HSPI (animals submitted to hypothermic ischemia and treated with 7.5% hypertonic saline solution preischemia), and HSPR (animals submitted to hypothermic ischemia and treated with hypertonic saline solution previously to liver reperfusion). Four hours after reperfusion, the animals were euthanized to collect liver and blood samples. RESULTS: Aspartate aminotransferase and alanine aminotransferase, histologic score, and hepatocellular necrosis were significantly decreased in animals submitted to hypothermia compared with the warm ischemia group. Malondialdehyde was significantly decreased in hypothermic groups with a further decrease when hypertonic saline solution was administrated preischemia. Hypothermic groups also showed decreased interleukin-6, interleukin-10, and tumor necrosis factor-α concentrations and better recovery of bicarbonate, base excess, lactate, and glucose blood concentrations. Moreover, hypertonic saline solution preischemia was more effective at controlling serum potassium concentrations. CONCLUSION: Hypertonic saline solution before hypothermic hepatic ischemia decreases hepatocellular oxidative stress, cytokine concentrations, and promotes better recovery of acid-base disorders secondary to liver ischemia reperfusion.


Subject(s)
Liver Diseases/prevention & control , Oxidative Stress/drug effects , Reperfusion Injury/prevention & control , Saline Solution, Hypertonic/therapeutic use , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Blood Glucose/analysis , Hypothermia, Induced/methods , Lipid Peroxidation/drug effects , Male , Rats , Rats, Wistar
2.
Gastroenterol Res Pract ; 2019: 5758984, 2019.
Article in English | MEDLINE | ID: mdl-31093276

ABSTRACT

OBJECTIVE: The inhalation anesthetic sevoflurane has presented numerous biological activities, including anti-inflammatory properties and protective effects against tissue ischemic injury. This study investigated the metabolic, hemodynamic, and inflammatory effects of sevoflurane pre- and postconditioning for short periods in the rescue of liver ischemia-reperfusion (IR) injury using a rat model. MATERIALS AND METHODS: Twenty Wistar rats were divided into four groups: sham group, control ischemia group (partial warm liver ischemia for 45 min followed by 4 h of reperfusion), SPC group (administration of sevoflurane 2.5% for 15 min with 5 min of washout before liver IR), and SPPoC group (administration of sevoflurane 2.5% for 15 min before ischemia and 20 min during reperfusion). RESULTS: All animals showed a decrease in the mean arterial pressure (MAP) and portal vein blood flow during ischemia. After 4 h of reperfusion, only the SPPoC group had MAP recovery. In both the SPC and SPPoC groups, there was a decrease in the ALT level and an increase in the bicarbonate and potassium serum levels. Only the SPPoC group showed an increase in the arterial blood ionized calcium level and a decrease in the IL-6 level after liver reperfusion. Therefore, this study demonstrated that sevoflurane preconditioning reduces hepatocellular injury and acid-base imbalance in liver ischemia. Furthermore, sevoflurane postconditioning promoted systemic hemodynamic recovery with a decrease in inflammatory response.

3.
Arq Gastroenterol ; 54(3): 246-249, 2017.
Article in English | MEDLINE | ID: mdl-28723980

ABSTRACT

BACKGROUND: Ischemia/reperfusion causes organ damage but it is mandatory in hepatic transplantation, trauma and other complex liver surgeries, when Pringle maneuver is applied to minimize bleeding during these procedures. It is well known that liver ischemia/reperfusion leads to microcirculatory disturbance and cellular injury. In this setting hypothermia is known to reduce oxygen demand, lowering intracellular metabolism. OBJECTIVE:: To evaluate the effects of hypothermia in liver ischemia/reperfusion injury, using a new model of topic isolated liver hypothermia. METHODS: We used male Wistar rats weighting about 250 grams, kept in ad libitum feeding regime and randomly divided into two groups of nine animals: 1) Normothermic group, rats were submitted to normothermic ischemia of the median and left hepatic lobes, with subsequent resection of right and caudate lobes during liver reperfusion; and 2) Hypothermic group, rats were submitted to liver ischemia under hypothermia at 10°C. Liver ischemia was performed for 45 minutes. The animals were euthanized 48 hours after liver reperfusion for blood and liver tissue sampling. RESULTS: The transaminases analyses showed a significant decrease of AST and ALT in Hypothermic group (P<0.01) compared to Normothermic group (1403±1234 x 454±213 and 730±680 x 271±211 U/L, respectively). Histology showed severe necrosis in 50% and mild necrosis in 50% of cases in Normothermic group, but severe necrosis in 10% and mild or absent necrosis 90% of the cases in hypothermic group. CONCLUSION:: A simplified model of liver ischemia/reperfusion that simulates orthotopic liver autotransplantion was demonstrated. Topical hypothermia of isolated hepatic lobules showed liver protection, being a viable and practical method for any kind of in vivo liver preservation study.


Subject(s)
Hypothermia, Induced , Liver Failure, Acute/prevention & control , Reperfusion Injury/complications , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Disease Models, Animal , Liver Failure, Acute/etiology , Liver Failure, Acute/pathology , Male , Necrosis , Rats , Rats, Wistar , Reperfusion Injury/pathology , Severity of Illness Index
4.
Arq. gastroenterol ; 54(3): 246-249, July-Sept. 2017. tab, graf
Article in English | LILACS | ID: biblio-888203

ABSTRACT

ABSTRACT BACKGROUND Ischemia/reperfusion causes organ damage but it is mandatory in hepatic transplantation, trauma and other complex liver surgeries, when Pringle maneuver is applied to minimize bleeding during these procedures. It is well known that liver ischemia/reperfusion leads to microcirculatory disturbance and cellular injury. In this setting hypothermia is known to reduce oxygen demand, lowering intracellular metabolism. OBJECTIVE: To evaluate the effects of hypothermia in liver ischemia/reperfusion injury, using a new model of topic isolated liver hypothermia. METHODS We used male Wistar rats weighting about 250 grams, kept in ad libitum feeding regime and randomly divided into two groups of nine animals: 1) Normothermic group, rats were submitted to normothermic ischemia of the median and left hepatic lobes, with subsequent resection of right and caudate lobes during liver reperfusion; and 2) Hypothermic group, rats were submitted to liver ischemia under hypothermia at 10°C. Liver ischemia was performed for 45 minutes. The animals were euthanized 48 hours after liver reperfusion for blood and liver tissue sampling. RESULTS The transaminases analyses showed a significant decrease of AST and ALT in Hypothermic group (P<0.01) compared to Normothermic group (1403±1234 x 454±213 and 730±680 x 271±211 U/L, respectively). Histology showed severe necrosis in 50% and mild necrosis in 50% of cases in Normothermic group, but severe necrosis in 10% and mild or absent necrosis 90% of the cases in hypothermic group. CONCLUSION: A simplified model of liver ischemia/reperfusion that simulates orthotopic liver autotransplantion was demonstrated. Topical hypothermia of isolated hepatic lobules showed liver protection, being a viable and practical method for any kind of in vivo liver preservation study.


RESUMO CONTEXTO: A isquemia/reperfusão leva a grave lesão de órgãos, mas ocorre obrigatoriamente no transplante hepático, no trauma e em outras cirurgias hepáticas complexas, quando a manobra de Pringle é aplicada com o intuito de minimizar o sangramento durante os procedimentos. É bem conhecido que a isquemia/reperfusão do fígado leva a distúrbios microcirculatórios e lesões celulares. Neste cenário, a hipotermia é conhecida por reduzir a demanda de oxigênio, diminuindo o metabolismo intracelular. OBJETIVO: Avaliar os efeitos da hipotermia na lesão de isquemia/reperfusão hepática utilizando-se um novo modelo de hipotermia isolada do fígado. MÉTODOS: Utilizaram-se ratos Wistar do sexo masculino com peso aproximado de 250 gramas, mantidos em regime de alimentação ad libitum e divididos aleatoriamente em dois grupos de nove animais: 1) Grupo Normotérmico - os ratos foram submetidos a isquemia normotérmica dos lobos hepáticos mediano e esquerdo, com posterior ressecção dos lobos direito e caudado durante a reperfusão hepática; e 2) Grupo Hipotérmico - os ratos foram submetidos a isquemia hepática sob hipotermia a 10°C. A isquemia hepática foi realizada durante 45 minutos. Os animais foram sacrificados 48 horas após a reperfusão hepática para coleta de sangue e tecido hepático para análise. RESULTADOS: As transaminases AST e ALT apresentaram diminuição significativa no grupo Hipotérmico (P<0,01) em relação ao grupo Normotérmico (1403±1234 x 454±213 e 730±680 x 271±211 U/L, respectivamente). A histologia mostrou necrose grave em 50% e necrose leve em 50% dos casos no grupo Normotérmico, porém, necrose grave em 10% e necrose leve ou ausente em 90% dos casos no grupo Hipotérmico. CONCLUSÃO: Foi demonstrado modelo simplificado de isquemia/reperfusão do fígado que simula o autotrasplante de fígado. A hipotermia tópica dos lóbulos hepáticos isolados mostrou proteção do fígado a ischemia/reperfusão, sendo um método viável e prático para qualquer tipo de estudo de preservação hepática in vivo.


Subject(s)
Animals , Male , Rats , Reperfusion Injury/complications , Liver Failure, Acute/prevention & control , Hypothermia, Induced , Aspartate Aminotransferases/blood , Severity of Illness Index , Reperfusion Injury/pathology , Rats, Wistar , Liver Failure, Acute/etiology , Liver Failure, Acute/pathology , Alanine Transaminase/blood , Disease Models, Animal , Necrosis
5.
PLoS One ; 11(2): e0149630, 2016.
Article in English | MEDLINE | ID: mdl-26901764

ABSTRACT

BACKGROUND: Ischemia and reperfusion (I/R) causes tissue damage and intracellular calcium levels are a factor of cell death. Sodium calcium exchanger (NCX) regulates calcium extrusion and Trisulfated Disaccharide (TD) acts on NCX decreasing intracellular calcium through the inhibition of the exchange inhibitory peptide (XIP). OBJECTIVES: The aims of this research are to evaluate TD effects in liver injury secondary to I/R in animals and in vitro action on cytosolic calcium of hepatocytes cultures under calcium overload. METHODS: Wistar rats submitted to partial liver ischemia were divided in groups: CONTROL: (n = 10): surgical manipulation with no liver ischemia; Saline: (n = 15): rats receiving IV saline before reperfusion; and TD: (n = 15): rats receiving IV TD before reperfusion. Four hours after reperfusion, serum levels of AST, ALT, TNF-α, IL-6, and IL-10 were measured. Liver tissue samples were collected for mitochondrial function and malondialdehyde (MDA) content. Pulmonary vascular permeability and histologic parameters of liver were determined. TD effect on cytosolic calcium was evaluated in BRL3A hepatic rat cell cultures stimulated by thapsigargin pre and after treatment with TD. RESULTS: AST, ALT, cytokines, liver MDA, mitochondrial dysfunction and hepatic histologic injury scores were less in TD group when compared to Saline Group (p<0.05) with no differences in pulmonary vascular permeability. In culture cells, TD diminished the intracellular calcium raise and prevented the calcium increase pre and after treatment with thapsigargin, respectively. CONCLUSION: TD decreases liver cell damage, preserves mitochondrial function and increases hepatic tolerance to I/R injury by calcium extrusion in Ca2+ overload situations.


Subject(s)
Calcium/metabolism , Liver Diseases/metabolism , Reperfusion Injury/metabolism , Animals , Capillary Permeability , Cytokines/blood , Disease Models, Animal , Hepatocytes/metabolism , Inflammation Mediators/blood , Liver Diseases/pathology , Liver Function Tests , Lung/metabolism , Male , Malondialdehyde/metabolism , Mitochondria, Liver/metabolism , Oxidation-Reduction , Phosphorylation , Rats , Reperfusion Injury/pathology , Sodium-Calcium Exchanger/metabolism
6.
ANZ J Surg ; 85(3): 174-8, 2015 Mar.
Article in English | MEDLINE | ID: mdl-24112413

ABSTRACT

BACKGROUND: Identification of molecular markers in pancreatic adenocarcinoma (PA) has the potential to guide targeted therapy. The objective of this study is to determine the prognostic significance of epidermal growth factor receptor (EGFR) expression (membrane and cytoplasmic) in resected PA and its correlation with lymph node metastasis and survival. METHODS: EGFR overexpression was determined by immunohistochemistry, and the pattern of expression was compared between the primary tumour, adjacent normal pancreas and involved lymph nodes. RESULTS: A total of 88 patients had curative resection. No difference was found in mEGFR overexpression between tumoural and metastatic nodal tissues (P = 0.28). Median overall survival time was 22.9 months. Overall cumulative 1-, 3- and 5-year survival was 48%, 20% and 18%, respectively. In positive mEGFR tumour expression, survival was 46% at 1 year, 8% at 3 years and 0% at 5 years (P < 0.05). Univariate analysis showed that male gender, portal vein (PV) resection, perineural, lymphovascular and peri-pancreatic invasion, positive margins and positive mEGFR expression in tumour tissue had worse survival. Multivariate analysis showed that male gender, PV resection, vascular and perineural invasion remained independent predictors of poor survival. CONCLUSION: Positive mEGFR overexpression is associated with decreased survival; however, it is not an independent prognostic factor.


Subject(s)
Adenocarcinoma/surgery , Biomarkers, Tumor/metabolism , ErbB Receptors/metabolism , Pancreatectomy , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Prognosis , Survival Analysis , Treatment Outcome
7.
Pancreas ; 43(6): 946-50, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24927360

ABSTRACT

OBJECTIVE: Pancreatic ischemia-reperfusion (IR) has a key role in pancreas surgery and transplantation. Most experimental models evaluate the normothermic phase of the IR. We proposed a hypothermic model of pancreas IR to evaluate the benefic effects of the cold ischemic phase. METHODS: We performed a reproducible model of hypothermic pancreatic IR. The ischemia was induced in the pancreatic tail portion (1-hour ischemia, 4-hour reperfusion) in 36 Wistar rats. They are divided in 3 groups as follows: group 1 (control), sham; group 2, normothermic IR; and group 3, hypothermic IR. In group 3, the temperature was maintained as close to 4.5°C. After reperfusion, serum amylase and lipase levels, inflammatory mediators (tumor necrosis factor α, interleukin 6), and pancreas histology were evaluated. RESULTS: In pancreatic IR groups, amylase, cytokines, and histological damage were significantly increased when compared with group 1. In the group 3, we observed a significant decrease in tumor necrosis factor α (P = 0.004) and interleukin 6 (P = 0.001) when compared with group 2. We did not observe significant difference in amylase (P = 0.867), lipase (P = 0.993), and histology (P = 0.201). CONCLUSIONS: In our experimental model, we reproduced the cold phase of pancreas IR, and the pancreas hypothermia reduced the inflammatory mediators after reperfusion.


Subject(s)
Cold Temperature , Hypothermia, Induced/methods , Pancreas/blood supply , Reperfusion Injury/physiopathology , Amylases/blood , Animals , Disease Models, Animal , Inflammation Mediators/blood , Interleukin-6/blood , Lipase/blood , Male , Pancreas/pathology , Rats, Wistar , Reperfusion Injury/blood , Time Factors , Tumor Necrosis Factor-alpha/blood
8.
Pancreatology ; 13(3): 225-9, 2013.
Article in English | MEDLINE | ID: mdl-23719592

ABSTRACT

BACKGROUND/OBJECTIVES: Colloid resuscitation in acute pancreatitis (AP) is a matter of controversy due to the possible deleterious effect on lung function. A previous study demonstrates that albumin administration increases lung damage in burns and this effect can be reversed by inducible nitric oxide synthase (iNOS) inhibition. This study evaluates the effects of S-methylisothiourea (SMT), a specific iNOS inhibitor, on lungs and pancreas of rats with AP receiving intravenous albumin. METHODS: AP was induced in Wistar rats by intraductal 5% taurocholate injection. To evaluate the effect of albumin on lung damage, animals received IV saline or human albumin immediately after AP (Groups: Saline and Albumin). To evaluate the effect of iNOS inhibition on lung damage, SMT was given immediately after AP (Group Saline+SMT, and Group Albumin+SMT). At 12 h after AP induction, serum amylase activity, lung vascular permeability and myeloperoxidase (MPO) activity were evaluated. Lung and pancreas histological analysis were performed. RESULTS: Serum amylase activity, pancreatic edema, lung vascular permeability, MPO activity, and inflammatory infiltration were significantly increased after AP. Albumin administration increased lung vascular permeability, inflammatory infiltration, and pancreatic edema compared to saline administration (p < 0.05). Albumin administration with SMT reduced lung vascular permeability, MPO activity, and inflammatory infiltration compared to albumin administration alone (p < 0.05). CONCLUSION: Lung and pancreatic damage induced by albumin administration for restoration of plasma volume in AP are reduced by iNOS inhibition. Awareness of this fact may be useful in high-risk patients who need to receive albumin for volume replacement.


Subject(s)
Albumins/adverse effects , Amylases/drug effects , Isothiuronium/analogs & derivatives , Lung/drug effects , Nitric Oxide Synthase Type II/antagonists & inhibitors , Pancreatitis/physiopathology , Amylases/blood , Animals , Capillary Permeability/drug effects , Isothiuronium/therapeutic use , Lung/pathology , Pancreatitis/chemically induced , Pancreatitis/drug therapy , Peroxidase , Rats , Rats, Wistar , Taurocholic Acid
9.
Arq. gastroenterol ; 40(3): 177-180, jul.-set. 2003. ilus, tab
Article in English | LILACS | ID: lil-356222

ABSTRACT

RACIONAL: O medicamento N2-mercaptopropionilglicina é um potente inibidor da síntese de radicais superóxidos e foi testado como agente preventivo de lesão metabólica e estrutural do parênquima hepático, no processo de isquemia/reperfusão. OBJETIVOS: Analisar alguns efeitos da administração do N2-mercaptopropionilglicina a animais de duas espécies submetidas a isquemia/reperfusão normotécnica do fígado. MATERIAL E MÉTODOS: Vinte e dois ratos e 22 cães foram divididos em quatro grupos: grupo I: ratos que receberam solução salina a 0,95 por cento; grupo II: ratos que receberam 100 mg/kg de N2-mercaptopropionilglicina; grupo III: cães que receberam salina a 0,9 por cento; grupo IV: cães que receberam 100 mg/kg de N2-mercaptopropionilglicina. Cada um dos grupos de animais foi, após 10 minutos da infusão tanto de salina, como de N2-mercaptopropionilglicina, submetidos a isquemia dos respectivos lobos esquerdos por um período de 25 minutos, seguida de reperfusão. RESULTADOS: Estudos bioquímicos, 24 horas após a reperfusão revelaram menor e significativa elevação das transaminases nos animais do grupo I (AST = 271 ± 182; ALT = 261 ± 161) e grupo IV (AST = 101 ± 45; ALT = 123 ± 89), quando comparados com os controles: grupo I (AST = 2144 ± 966; ALT = 1869 ± 1040) e grupo III (AST = 182 ± 76; ALT = 277 ± 219), respectivamente e todos em UI/dL. O estudo histológico demonstrou agressão significativamente menor nos animais dos grupos experimentais II e IV, quando comparados aos grupo I e grupo III, respectivamente. CONCLUSAO: Estes resultados sugerem liberação de radicais livres de oxigênio real e significativa no processo e que o N2-mercaptopropionilglicina pode ter efeito protetor apreciável no parênquima hepático, quando submetido a isquemia e posterior reperfusão.


Subject(s)
Animals , Male , Dogs , Rats , Antioxidants , Ischemia , Liver , Reperfusion Injury , Alanine Transaminase , Cytoprotection , Liver , Rats, Wistar
10.
Pancreas ; 26(3): 230-4, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12657947

ABSTRACT

INTRODUCTION: Some studies demonstrate the crucial role of proteases in the pathogenesis of acute pancreatitis (AP). Systemic release of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) has been demonstrated in AP, yet the mechanism of activation remains unclear. Furthermore, it is not known if the amount of pancreatic enzyme in the pancreas determines the production of proinflammatory cytokines. AIM: To determine whether there is a link between the pancreatic enzyme content and the production of cytokines and consequently the systemic lesions observed in AP. METHODOLOGY: Forty-seven animals were divided into three groups: group I had a high pancreatic enzyme level (with and without AP), group II had a low pancreatic enzyme level (cerulein infusion: 0.133 microg x kg(-1) x h(-1)) (with and without AP), and group III were the controls. AP was induced by injection of 5% sodium taurocholate into the pancreatic duct. To evaluate the pancreatic enzyme contents before AP, trypsinogen and amylase analysis was carried out on pancreatic tissue collected after the animals were killed. Two hours after induction of AP, concentrations of pancreatic enzymes and trypsinogen activation peptide (TAP) in serum, ascitic fluid, and pancreatic tissue were determined. The ascitic fluid was assayed for TNF-alpha and the serum was assayed for IL-6 with ELISA kits. Systemic lesions were sought on the basis of hepatic mitochondrial respiratory function measured polarographically. RESULTS AND CONCLUSION: The administration of physiological doses of cerulein diminishes the pancreatic enzyme and TAP levels, the production of proinflammatory cytokines, and the liver mitochondrial dysfunction observed in AP, suggesting that the pancreatic enzyme content is an important factor in the severity of AP.


Subject(s)
Pancreas/enzymology , Pancreatitis/enzymology , Acute Disease , Animals , Interleukin-6/biosynthesis , Male , Mitochondria, Liver/metabolism , Oligopeptides/analysis , Oxidation-Reduction , Pancreatitis/immunology , Pancreatitis/pathology , Phosphorylation , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha/biosynthesis
11.
Arq Gastroenterol ; 40(3): 177-80, 2003.
Article in English | MEDLINE | ID: mdl-15029394

ABSTRACT

BACKGROUND: N2-mercaptopropionylglycine is a powerful super oxide synthesis inhibitor and has been tested as a preventive agent of metabolic and structural hepatic damage in the ischemia/reperfusion process. AIM: To analyze some effects of N2-mercaptopropionylglycine administration to animals of two species submitted to normothermic liver ischemia/reperfusion. MATERIAL AND METHODS: Twenty-two rats and 22 dogs were divided into four groups: group I: rats that received intravenous saline 0.9%; group II: rats that received 100 mg/kg of N2-mercaptopropionylglycine; group III: dogs that received saline intravenous 0.9% and group IV: dogs that received 100 mg/kg N2-mercaptopropionylglycine. RESULTS: Ten minutes after the saline or drug administration, each group was submitted to left lobe liver ischemia for 25 minutes followed by reperfusion. Biochemical studies 24 hours after reperfusion revealed a significantly lower elevation of transaminases in animals of groups II (AST = 271 +/- 182; ALT = 261 +/- 161 ) and IV (AST = 101 +/- 45; ALT = 123 +/- 89) when compared to the controls group: I (AST = 2144 +/- 966; ALT = 1869 +/- 1040 00) and III (AST = 182 +/- 76.51; ALT = 277 +/- 219), respectively. Histology study demonstrated a significantly minor aggression to animals of groups II and IV when compared to groups I and III, respectively. CONCLUSION: These results suggest a significant release of free radicals of oxygen in the process and that N2-mercaptopropionylglycine may have a significant protective effect on liver parenchyma when submitted to ischemia/reperfusion.


Subject(s)
Antioxidants/pharmacology , Ischemia/drug therapy , Liver/blood supply , Reperfusion Injury/prevention & control , Tiopronin/pharmacology , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Cytoprotection/drug effects , Dogs , Male , Rats , Rats, Wistar
12.
JOP ; 3(5): 144-51, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12221329

ABSTRACT

OBJECTIVE: To clarify the sensitivity and the validity of K-ras point mutational analysis at codon 12 in Brazilian patients with pancreatic diseases, and the possible correlation between the presence of the mutation and the histopathological findings. PATIENTS: Ninety-seven Brazilian patients with pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumors and chronic pancreatitis were enrolled in this study. Forty-five patients (46%) were female and 52 patients (54%) were male, having an average age of 60.2+/-9.2 years for adenocarcinoma (n=52), 45.1+/-19.4 years for pancreatic neuroendocrine tumors (n=20), and 46.4+/-11.2 years for chronic pancreatitis (n=25). DNA extracted from 11 normal human peripheric lymphocytes was utilized as a control. RESULTS: The sensitivity of K-ras mutational analysis was 83.3% (25/30) in paraffin-embedded samples and 72.7% (16/22) in surgically resected specimens of the malignancy. On the other hand, no mutations were found in pancreatic neuroendocrine tumors or in chronic pancreatitis. Regarding the histopathological grading, the higher positivity rate was found in poorly-differentiated adenocarcinoma (100%), and progressively decreased in moderately-differentiated adenocarcinoma (72.2%), and well-differentiated adenocarcinoma (66.6%). The positivity rate in non-classified adenocarcinoma was 81.8%. CONCLUSION: K-ras point mutation, in our study, is notably prevalent in malignancies and is absent in chronic pancreatitis and pancreatic neuroendocrine tumors. These results encourage us to consider the possibility of treatment strategies for this oncogene in the future.


Subject(s)
Codon/genetics , Genes, ras/genetics , Pancreatic Diseases/genetics , Point Mutation/genetics , Adenocarcinoma/genetics , Adult , Aged , Aged, 80 and over , Brazil , Chronic Disease , DNA Mutational Analysis/methods , Female , Humans , Male , Middle Aged , Neuroendocrine Tumors/genetics , Pancreatic Ducts/chemistry , Pancreatic Ducts/metabolism , Pancreatic Ducts/pathology , Pancreatic Neoplasms/genetics , Pancreatitis/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Sensitivity and Specificity
13.
Rev. Hosp. Clin. Fac. Med. Univ. Säo Paulo ; 53(4): 169-73, jul.-ago. 1998. ilus, tab
Article in Portuguese | LILACS | ID: lil-228056

ABSTRACT

O N2-Mercaptopropionilglicina (MPG) e um potente antioxidante na inibicao da producao de xantina-oxidase. O objetivo deste trabalho foi analisar se este efeito antioxidante poderia propiciar menor agressao do tecido pancreatico na Pancreatite Aguda (PA) induzida por dois processos: dose supramaxima de ceruleina e injecao de taurocolato de sodio a 2,5 por cento no ducto biliopancreatico do rato. Trinta e seis ratos machos Wistar (220-270 g) foram divididos em 2 grupos (G): GI-animais previamente tratados com antioxidante (MPG: 100 mg/kg) 10 minutos antes da inducao da PA e GII-animais sem tratamento previo. Os animais destes dois grupos foram submetidos a PA com dose supramaxima de ceruleina (2 doses de 20ug/kg) e PA com taurocolato onde vinte e seis ratos foram divididos em dois grupos (G): GIII-ratos tratados com MPG 10 minutos antes da PA e GIV-animais sem tratamento previo...


Subject(s)
Animals , Rats , Male , Pancreatitis/chemically induced , Tiopronin/therapeutic use , Acute Disease , Antioxidants/therapeutic use , Capillary Permeability/drug effects , Free Radicals , Pancreatitis/therapy , Rats, Wistar
14.
Rev. med. (Säo Paulo) ; 77(2): 67-86, mar.-abr. 1998. ilus, tab
Article in Portuguese | LILACS | ID: lil-224965

ABSTRACT

Um potente inibidor da sintese de radicais superoxidos, a N2-Mercaptopropionilglicina (N2-MPG), principalmente radicais hidroxila (OH), foi testado como agente preventivo na degradacao metabolica e estrutural do parenquima hepatico no processo de isquemia/reperfusao testando a hipotese de participacao significativa da superoxidacao na necrose do figado. Para tanto foram utilizados 22 ratos e 22 caes, distribuidos em dois grupos. Grupo I com administracao de solucao salina 0,9 por cento e Grupo II (GII) com administracao de N2-MPG. As amostras foram submetidas a estudo laboratorial, radiologico, anatomopatologico e estatistico. Os resultados revelaram uma elevacao das transaminases significativamente menor nos animais tratados com N2-MPG...


Subject(s)
Animals , Cats , Dogs , Male , Tiopronin/adverse effects , Liver Circulation , Reperfusion Injury/metabolism , Free Radicals/pharmacokinetics , Antioxidants/metabolism , Preoperative Care/methods , Liver/pathology , Reperfusion Injury/physiopathology
15.
ABCD (São Paulo, Impr.) ; 12(1/2): 10-3, 1997. tab
Article in English | LILACS | ID: lil-224960

ABSTRACT

O carcinoma incidental da vesicula biliar foi estudado em pecas de 475 doentes submetidos a colecistectomia por litiase e relacionado com a faixa etaria. O cancer foi encontrado em oito pacientes (1,68 por cento) e correlacionou-se com idade (5,71 por cento acima de 60 anos). Foi encontrado em estagio avancado em 75 por cento dos casos e somente em um caso foi diagnosticado no exame macroscopico pelo cirurgiao e patologista. A colecistectomia eletiva deve ser sempre considerada em pacientes com colelitiase que estejam em faixa etaria acima da sexta decada


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Carcinoma , Gallbladder Neoplasms/epidemiology , Cholecystectomy , Choledochal Cyst/diagnosis , Cholelithiasis/diagnosis , Diagnosis, Differential , Gallbladder Neoplasms/diagnosis
16.
Rev. Hosp. Clin. Fac. Med. Univ. Säo Paulo ; 51(6): 228-31, nov.-dez. 1996. ilus, tab
Article in Portuguese | LILACS | ID: lil-186834

ABSTRACT

A possivel relaçäo causal entre insuficiência renal mioglobinurica (rabdomiolise) e lesäo hepatica ainda nao esta bem definida e foi objeto deste estudo. Ratos machos (220-270 g) foram privados de agua por 24 horas e divididos em dois grupos: GI-animais experimentais em que a rabdomiolise foi induzida mediante injeçäo intramuscular de glicerol a 50 por cento na dose de 10 ml/kg. GII-animais controles que receberam injecao intramuscular de solucao salina. Vinte e quatro horas apos a injecao todos os animais foram sacrificados. No sangue colhido foram dosados AST, ALT, CK, ureia e creatinina. Os figados foram removidos para estudo histologico e para avaliacao da funcao mitocondrial, determinada polarograficamente com eletrodo de Clark, medindo-se o consumo de oxigenio na ausencia de ADP (S4-Basal) e na presenca de ADP (S3-Ativado). A razao do controle respiratorio (RCR) e relacao ADP/O foram calculadas...


Subject(s)
Animals , Male , Rats , Mitochondria, Liver/pathology , Rhabdomyolysis/diagnosis , Renal Insufficiency/pathology , Myoglobinuria/diagnosis
17.
Rev. Hosp. Clin. Fac. Med. Univ. Säo Paulo ; 51(4): 113-5, jul.-ago. 1996.
Article in Portuguese | LILACS | ID: lil-186807

ABSTRACT

A utilizaçäo ou näo de drenagem após colecistectomias convencionais eletivas tem sido objeto de estudos recentes e ainda se discute a real incidência de coleçäo biliar sub hepatica e seu significado clinico. Neste sentido estudamos vinte pacientes com idade média de 45 anos (4 sexo masculino; 16 sexo feminino), com diagnóstico pré e intra-operatório de colecistite crônica calculosa, submetidos a colecistectomias eletivas conforme técnica padronizada pelo nosso grupo, em que säo realizadas ligaduras de todos os vasos do leito vesicular e drenagem do espaco sub hepático. Estes pacientes recebiam, 99m Tecnecio-DISIDA endovenoso no momento em que se completava o fechamento da parede abdominal e por periodo de 24 e 48 horas estudou-se a presença deste marcador no espaço sub hepatico e no material drenado. Todos os pacientes tiveram evoluçäo pós-operatória sem intercorrencias e nenhuma drenagem de liquido biliar ou coleçäo sub hepática visivel no mapeamento...


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Biliary Fistula , Cholecystectomy , Cholecystitis , Drainage , Cystic Duct/surgery , Technetium
18.
Rev. Hosp. Clin. Fac. Med. Univ. Säo Paulo ; 51(3): 93-5, maio-jun. 1996. tab
Article in Portuguese | LILACS | ID: lil-186845

ABSTRACT

Foram estudados retrospectivamente 221 pacientes submetidos a colecistectomia convencional entre 03/1987 e 03/1992, dados referentes ao tipo de cirurgia, complicacoes e mortalidade foram analisados. Cento e setenta e um pacientes (77,3 por cento) foram submetidos a colecistectomia (C) simples, 29 (13,1 por cento) a C e coledocotomia, 17 (7,6 por cento) a C e papiloesfincteroplastia e 4 (2 por cento) a C e anastomose bilio digestiva. As complicacoes mais frequentes foram pulmonares, urinarias e infeccao de incisao. A incidencia geral de complicacoes foi de 7,2 por cento...


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Cholecystectomy , Cholelithiasis/diagnosis , Gallbladder/physiopathology , Hospitals, Teaching
19.
GED gastroenterol. endosc. dig ; 14(2): 59-64, maio-jun. 1995. tab
Article in Portuguese | LILACS | ID: lil-172077

ABSTRACT

O objetivo deste trabalho foi analisar a lesäo hepática desenvolvida durante a PA através do estudo da funçäo mitocondrial hepática. Para tanto, 54 ratos machos Wistar foram distribuídos em seis grupos: GI (controle n=6), GII (PA duas horas n=12), GIII (PA quatro horas n=6), GIV (PA 12 horas n=8), GV (PA 24 horas n=7) e GVI (PA 48 horas n=7). A PA foi induzida por injeçäo retrógrada de taurocolato de sódio a 5 por cento. A avaliaçäo da funçäo mitocondrial hepática foi determinada polarograficamente com eletrodo de Clark, medindo-se o consumo de O2 na ausência de ADP (S4-basal) e na presença de ADP (S3 ativado), utilizando-se succinato de potássio como sunstrato. A razäo do controle respiratório (RCR) e a relaçäo ADP/O foram calculadas. Na fase precoce da PA (duas e quatro horas), existe desacoplamento das mitocôndrias evidenciado por aumento do S4 e diminuiçäo do RCR e da relaçäo ADP/O, No período de 12 e 24 horas após a PA, o RCR apresenta valores iguais aos do controle. Conclui-se que as alteraçöes mitocondriais na PA säo bifásicas: as alteraçöes precoces säo caracterizadas por desacoplamento da oxigenaçäo fosforilativa e talvez resulte da açäo à distância de enzimas de produtos da açäo enzimática, enquanto as alteraçöes tardias säo decorrentes de lesöes estruturais e graves, resultantes de isquemia tecidual. Estudos hemodinâmicos devem ser efetuados para esclarecer estas alteraçöes


Subject(s)
Animals , Male , Rats , Amylases/analysis , Ascitic Fluid/chemistry , Mitochondria, Liver , Pancreatitis/chemically induced , Proteins/analysis , Trypsin/analysis , Acute Disease , Disease Models, Animal , Polarography , Rats, Wistar
20.
Rev. Hosp. Clin. Fac. Med. Univ. Säo Paulo ; 49(6): 246-9, nov.-dez. 1994. tab
Article in Portuguese | LILACS | ID: lil-154398

ABSTRACT

Os tumores cisticos do pancreas representam cerca de 9 por cento a 13 por cento de todas lesoes cisticas do pancreas, cerca de 1 por cento das neoplasias pancreaticas e sao predominantes em pacientes do sexo feminino. Uma falha em reconhecer a natureza neoplasica de uma lesao cistica do pancreas pode levar a uma terapeutica incorreta. Este trabalho tem o objetivo de relatar cinco pacientes com tumor cistico que foram erroneamente tratados inicialmente como pseudocisto do pancreas. A idade dos pacientes variou entre 21 e 71 anos, com media de 46 anos. Dos cinco pacientes, tres eram portadores de cistadenoma mucinoso e dois eram portadores de cistadenocarcinoma....


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Cystadenoma/diagnosis , Pancreatic Neoplasms/diagnosis , Pancreatic Pseudocyst/diagnosis , Cystadenocarcinoma/diagnosis , Diagnostic Errors , Pancreatic Neoplasms/surgery , Pancreatectomy , Signs and Symptoms
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