Expression of Fas (CD95/APO-1) and Fas ligand (FasL) in experimentally-induced acute pancreatitis.

INTRODUCTION: Acinar cell death is a crucial event in acute pancreatitis (AP) and may occur either by apoptosis or necrosis. The aim of this study was to investigate the expression of the apoptosis associated proteins Fas and FasL in experimentally induced severe AP. METHODS: AP was induced in 30 rats by injecting 0.2 ml of 4.5% sodium taurocholate solution into the biliopancreatic duct. Sham operated animals (n = 30) and 10 normal controls were used for comparisons. Animals were killed at 6, 12, 24, 48, 72 hr and 1 week after operation (five animals at each time point) and both serum and pancreatic tissue were obtained. The severity of AP was graded by morphological evaluation and by measuring serum amylase levels. Acinar cell apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Tissue expressions of Fas and FasL were evaluated by immunohistochemistry. RESULTS: Sodium taurocholate injection resulted in severe acute necrotizing pancreatitis as early as six hr after taurocholate infusion with gradually increasing severity and a peak at 72 hr, and a significant increase of serum amylase at 6 and 12 hr. Apoptotic acinar cells were observed between 48 and 72 hr. The expression of both Fas and FasL in pancreatic tissue was induced in comparison with normal controls. Fas expression in AP was higher and statistically significant at 24 hr whereas FasL expression was consistently lower with a statistical significance observed at 12 hr when compared to sham-operated animals suggesting Fas upregulation and FasL downregulation in this model of AP. CONCLUSIONS: Induction and sequential changes in the expressions of Fas and FasL occur during taurocholate induced severe AP in rats and their temporal modulation might associate with acinar cell death by apoptosis.

Corticotropin-releasing hormone receptors mediate opposing effects in cholestasis-induced liver cell apoptosis.

CRH receptors are expressed in human and rat liver. The current study investigated the biological role of the CRH system in the hepatocellular apoptotic process and aimed to reveal the responsible molecular mechanisms. Using a rat experimental model of common bile duct surgical ligation leading to obstructive jaundice and cholestasis, liver apoptosis was induced in the hepatic parenchyma as confirmed by the elevated expression of the early apoptotic neoepitope M30. This effect was reversed by administration of the nonselective CRH antagonist astressin but not by the selective CRH(2) antagonist astressin2B, suggesting that antagonism of the endogenous CRH(1) blocked the cholestasis-induced apoptotic mechanism. No effect was observed in the noncholestasis controls. In our experimental model, early and late apoptosis-preventing markers were induced in parallel to apoptosis; elevated gene transcript levels of the anti-apoptotic bcl-2 were found by real-time PCR in the first postoperative day and increased serum hepatocyte growth factor levels were measured by ELISA in the third postoperative day. Selective CRH(2) antagonism reversed the elevated expression of bcl-2 and hepatocyte growth factor, suggesting that this receptor type mediated antiapoptotic actions of the endogenous CRH system, opposing the preapoptotic ones mediated by CRH(1). In conclusion, the present study indicated that the CRH neuroendocrine system regulates cholestasis-induced apoptosis in the hepatic parenchyma via receptor-specific pathways. These data may contribute to better understanding of the CRH biology and its pathophysiological significance in the periphery.

Human leptin induces angiogenesis in vivo.

Leptin is an adipocyte-produced peptide, which plays a crucial role in the regulation of body weight. There is also evidence that leptin stimulates endothelial cell proliferation and the formation of capillary-like tubes in vitro. The disc angiogenesis system was used to measure the angiogenic effect of leptin in vivo. Discs containing 25, 50, 100 and 250ng/ml of leptin were implanted subcutaneously in Wistar rats, removed after a growth period of 7 and 14 days, and compared with spontaneous growth controls and with positive controls containing equivalent doses of vascular endothelial growth factor (VEGF). Discs were examined morphologically for stroma and vessel development and by immunohistochemistry for quantitative evaluation of angiogenesis. The specificity of the angiogenic effect of leptin was tested by blocking leptin with a polyclonal anti-leptin antibody. Leptin induced a significant level of angiogenesis in a dose-dependent manner both at 7 and 14 days, with a peak at the dose of 100ng/ml. The angiogenic activity of leptin was completely abolished by the anti-leptin neutralizing antibody. VEGF also induced significant dose-dependent angiogenesis at the same time points with a peak observed at a concentration of 100ng/ml. The angiogenic response to leptin was significantly higher at 7 days compared with VEGF but not at the 14-day time point. In conclusion, leptin has a specific angiogenic effect in vivo, which is dose- and time-dependent in a concentration range of 25-250ng/ml. This effect is equivalent to the angiogenic effect of VEGF but is evident earlier compared with VEGF.

Burn wound angiogenesis is increased by exogenously administered recombinant leptin in rats.

BACKGROUND: Leptin is a potent direct angiogenic factor that stimulates endothelial cell migration and activation in vitro and angiogenesis in vivo. In addition, leptin has been discussed to play an important role in angiogenesis, as it promotes the formation of new blood vessels. PURPOSE: The effect of exogenously administered leptin on the healing process of a full tissue burn wound model. METHODS: Sixty-three Sprague-Dawley male rats were used. Full tissue burn wound was created by electrocautery. The width of the pin was 0.3 cm; its length was 2 cm and was used at the "cut" modulation. Rats were divided into seven groups of nine animals each. Burn wounds were injected with murine recombinant leptin and the rats were sacrificed 3, 7 and 9 days after surgery. Every group had obtained three animals for the three different days of sacrifice. Three different leptin doses of 250 pg/ml, 500 pg/ml and 1000 pg/ml were used in different animal groups (A, B and C). For every one of the three leptin doses used, another animal group was evaluated by using the combined injection of leptin and antileptin (A1, B1, and C1), in order to study the inhibitory effect to the leptin factor. Nine rats were served as controls. These were injected with 0.3 ml water for injection solution and sacrificed at the same time intervals. After sacrifice of the animals, the skin was grossly determined by its appearance, colour and texture. Full thickness burn wounds were dissected for histological examination. A qualitative analysis of angiogenesis in the burn wound was conducted following a standard hematoxylin and eosin stain. The wound tissue samples from each experimental group underwent immunohistochemical evaluation of microvessel density by endothelial cell staining with mouse anti-rat CD 34 monoclonal antibody. RESULTS: The most impressive growth of new blood vessels appeared seven and nine days after treatment with the highest leptin doses. There were no significant differences in microvessel density between the seventh and the ninth postoperative day among different groups treated with leptin. All wounds from the control group, as well as those from animal groups treated with the combined injection of leptin and antileptin did not develop any new vessels. CONCLUSION: Exogenous administration of recombinant leptin increases early tissue angiogenesis in the burn wound level of an experimental animal model.

Burn wound angiogenesis is increased by exogenously administered recombinant leptin in rats

BACKGROUND: Leptin is a potent direct angiogenic factor that stimulates endothelial cell migration and activation in vitro and angiogenesis in vivo. In addition, leptin has been discussed to play an important role in angiogenesis, as it promotes the formation of new blood vessels. PURPOSE: The effect of exogenously administered leptin on the healing process of a full tissue burn wound model. METHODS: Sixty-three Sprague-Dawley male rats were used. Full tissue burn wound was created by electrocautery. The width of the pin was 0.3 cm; its length was 2 cm and was used at the "cut" modulation. Rats were divided into seven groups of nine animals each. Burn wounds were injected with murine recombinant leptin and the rats were sacrificed 3, 7 and 9 days after surgery. Every group had obtained three animals for the three different days of sacrifice. Three different leptin doses of 250 pg/ml, 500 pg/ml and 1000 pg/ml were used in different animal groups (A, B and C). For every one of the three leptin doses used, another animal group was evaluated by using the combined injection of leptin and antileptin (A1, B1, and C1), in order to study the inhibitory effect to the leptin factor. Nine rats were served as controls. These were injected with 0.3 ml water for injection solution and sacrificed at the same time intervals. After sacrifice of the animals, the skin was grossly determined by its appearance, colour and texture. Full thickness burn wounds were dissected for histological examination. A qualitative analysis of angiogenesis in the burn wound was conducted following a standard hematoxylin and eosin stain. The wound tissue samples from each experimental group underwent immunohistochemical evaluation of microvessel density by endothelial cell staining with mouse anti-rat CD 34 monoclonal antibody. RESULTS: The most impressive growth of new blood vessels appeared seven and nine days after treatment with the highest leptin doses. There were no significant...

INTRODUÇÃO: A leptina é um potente fator angiogênico que estimula a migração e a ativação de células endoteliais in vitro e a angiogênese in vivo. Além disso, a leptina tem sido considerada importante na angiogênese pois ela promove a formação de novos vasos sanguíneos. OBJETIVO: Investigar o efeito da leptina administrada por via exógena no processo de cicatrização em um modelo experimental de queimadura. MÉTODOS: Foram utilizados sessenta e três ratos Sprague-Dawley, machos. A lesão de espessura total da queimadura foi realizada por eletrocautério. O dano tecidual foi de 0.3 cm numa extensão de 2 cm tendo sido empregada o módulo de "corte"do eletrocautéio. Os ratos foram distribuídos em sete grupos de nove animais. As lesões por queimadura receberam leptina recombinante. Os animais foram sacrificados 3, 7 e 9 dias após o ato operatório. Obteve-se três animais de cada grupo nos três períodos estipulados. Três diferentes dosagens de leptina: 250 pg/ml, 500 pg/ml e 1000 pg/ml foram aplicados nos três diferentes grupos (A, B e C). Para cada uma das três dosagens de leptina, outro grupo de animais foi avaliado pelo uso de injeção combinada de leptina e antileptina (A1, B1 e C1) no sentido de investigar o efeito inibitório do fator leptina. Nove ratos serviram de controles. Estes foram submetidos à injeção de 0.3 ml de água e sacrificados nos mesmos intervalos de tempo. Após o sacrifício dos animais, o tegumento foi avaliado por sua aparência, cor e textura. Fragmentos das feridas queimadas foram ressecadas para exame histológico. A análise qualitativa de angiogênese, na ferida queimada, seguia o padrão da coloração de hematoxilina e eosina. Cada fragmento de tecido, de cada grupo experimental, foi submetido à avaliação imunohistoquímica da densidade dos microvasos pela coloração da célula endotelial por anti-rato CD 34 anticorpo monoclonal. RESULTADOS: O desenvolvimento de novos vasos sanguíneos foi mais significativo após sete e nove dias...

Land mine injuries in the northernmost border of Greece: our experience at the University Hospital of Alexandroupolis during 1991-2003.

We studied the mortality and morbidity caused by land mine injuries in 169 cases that presented at the University General Hospital of Thrace, Alexandroupolis, Greece, during the period of 1991 to 2003. The data analyzed included the emergency room records, the admission records, and the autopsy records from the coroner that provided information on cause of death either in the prehospital phase, the initial treatment, or during the period following definitive surgical repair. Eleven percent of the casualties were lethally injured, the majority of whom died before reaching the hospital. Twenty-eight percent suffered severe injuries that required hospitalization and surgical management, placing an organizational and financial strain upon the hospital's resources, and 40% bore light injuries requiring only ambulatory treatment in the emergency room.

Axial torsion and gangrene of a giant Meckel's diverticulum.

A variety of complications are related to a Meckel's diverticulum, including hemorrhage, intestinal obstruction and inflammation. Axial torsion and gangrene of Meckel's diverticulum is the rarest of the complications that have been reported, with this being particularly true in case of children. We report a case of axial torsion and gangrene of a giant Meckel's diverticulum in a 6 year old child.

Spontaneous resolution of massive right-sided pneumothorax occurring during laparoscopic cholecystectomy.

Pneumothorax is a rare but potentially serious complication that can occur during laparoscopic surgery. We describe a case of a spontaneous massive right-sided pneumothorax that occurred during laparoscopic cholecystectomy, presumably because of escape of intraperitoneal carbon dioxide under pressure into the pleural cavity through a congenital defect in the diaphragm. During the procedure, arterial oxygen saturation decreased and clinical examination revealed signs of a right-sided pneumothorax. This was confirmed on chest x-ray in the immediate postoperative period. Since the patient was clinically stable without any signs of respiratory distress, a conservative approach was adopted. The patient remained on close clinical observation and continuous monitoring of arterial hemoglobin oxygen saturation by pulse oximetry and repeat chest x-rays and had an uneventful recovery with complete resolution of the pneumothorax 3 hours after surgery and without the need for thoracic aspiration or tube thoracostomy.

Serum levels of c-erbb-2 correlate with advanced stage and liver metastasis in colorectal cancer.

OBJECTIVE: To study the clinical significance of soluble c-erbB-2 in the serum of patients with colorectal cancer. METHODS: Serum c-erbB-2 levels were measured by an enzyme-linked immunosorbent assay in 52 patients with colorectal cancer and in 35 healthy controls. Their association with clinicopathological features, serum carcinoembryonic antigen (CEA) and patient survival was also evaluated. RESULTS: Serum c-erbB-2 levels in colorectal cancer patients were significantly higher than those in controls and correlated significantly with Dukes' stage and with the presence of liver metastases. Patients with elevated serum c-erbB-2 levels showed shorter survival compared with those with normal serum c-erbB-2 levels although the difference was not statistically significant. There was no relationship between serum c-erbB-2 and CEA levels. Elevated serum c-erbB-2 levels showed a moderate specificity and a low sensitivity in colorectal cancer diagnosis with their sensitivity being lower compared with the sensitivity of CEA. CONCLUSION: Serum c-erbB-2 levels in colorectal cancer patients are significantly higher compared with healthy controls and correlate with advanced disease stage and the presence of liver metastases. However, their clinical usefulness remains questionable.

Esophageal and small bowel obstruction by occupational bezoar: report of a case.

BACKGROUND: Phytobezoar may be a cause of bowel obstruction in patients with previous gastric surgery. Most bezoars are concretions of poorly digested food, which are usually formed initially in the stomach. Intestinal obstruction (esophageal and small bowel) caused by an occupational bezoar has not been reported. CASE PRESENTATION: A 70-year old male is presented suffering from esophageal and small bowel obstruction, caused by an occupational bezoar. The patient has worked as a carpenter for 35 years. He had undergone a vagotomy and pyloroplasty 10 years earlier. The part of the bezoar, which caused the esophageal obstruction was removed during endoscopy, while the part of the small bowel was treated surgically. The patient recovered well and was discharged on the 8th postoperative day. CONCLUSIONS: Since occupational bezoars may be a cause of intestinal obstruction (esophageal and/or small bowel), patients who have undergone a previous gastric surgery should avoid occupational exposures similar to the presented case.

Serum vascular endothelial growth factor levels in pancreatic cancer patients correlate with advanced and metastatic disease and poor prognosis.

The serum concentrations of vascular endothelial growth factor (VEGF) were measured by an enzyme linked immunosorbent assay in 51 healthy controls and in 58 patients with pancreatic cancer before and 30 days after surgery. Pancreatic cancer patients had significantly higher serum VEGF levels compared with healthy controls with a significant association between serum VEGF levels, disease stage and the presence of both lymph node and distant metastases. Serum levels of VEGF decreased significantly after radical resection of the tumor. Elevated preoperative serum VEGF level was a significant prognostic factor, although not independent of stage, for patient survival. These findings suggest that serum VEGF concentrations may reflect pancreatic cancer progression and that their determination may be clinically useful.