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Introduction: we present a rat experimental model used to evaluate the possible reduction in the extent of pancreatic tissue injury in acute pancreatitis cases, after administration of eugenol. Methods: one hundred and twenty Wistar rats were used, which were randomly assigned in 3 groups: sham (n=20), control (n=50) and eugenol (n=50). Acute pancreatitis was induced by biliopancreatic ligation in the control and eugenol groups, but not in the Sham group. In the eugenol group, eugenol was administered per-os. Five histopathological parameters, such as edema, inflammatory infiltration, duct dilatation, hemorrhage and acinar necrosis were evaluated. Results: at 72 h from acute pancreatitis induction, the total histological score was diminished in the eugenol group (p<0.0005) and duct dilatation and inflammatory infiltration were reduced compared to the control group (p<0.05). In addition, at 72 h, eugenol reduced pancreatic myeloperoxidase activity (p<0.0005). Conclusion: eugenol, a highly free radical scavenger agent, may have a preventive role in acute pancreatic injury, as it was evident in our rat experimental model. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Despite the important progress observed in liver surgery, the survival rates are discouraging. The aim of this study was to investigate the expression of autotaxin in hepatocellular carcinoma. Materials and Methods: Liver tissues from 28 human hepatocellular carcinomas were evaluated for the expression of autotaxin by immunohistochemistry. The gender, age, histological grade, lymphovascular invasion, number of tumors, levels of serum alpha-fetoprotein (aFP), presence of liver cirrhosis, hepatitis, surgery and survival rates were recorded. Results: Immunohistochemistry confirmed the expression of autotaxin in hepatocellular carcinoma. The histological grade seems to be the only independent predictor of stronger autotaxin expression, as significantly higher levels of autotaxin were detected in histological grades II and III. In addition, levels of autotaxin seem to be the most important independent prognostic factor related to poor survival. There was an eight-fold higher risk of death in patients with high levels of autotaxin compared to patients with low levels. Conclusions: Autotaxin expression in hepatocellular carcinoma could be of great importance. High autotaxin expression in HCC is detected in patients with histological grade II and III. Further, patients with elevated expression levels were found to possess an eight-fold higher risk of death. Autotaxin role in HCC should be further elucidated. [ABSTRACT FROM AUTHOR]

Purpose/aim: To examine with immunohistochemical assay MTA1 protein expression levels in pancreatic cancer tissues defining its prognostic value. Material and Methods: The specimens derived from 51 patients who underwent surgery. The levels of MTA1 protein were compared with the age of the patients, their survival, and prognosis. Also, we studied clinical and histopathological factors such as the degree of tumor differentiation and its stage in correlation with MTA1 protein levels. In parallel, there was correlation between the expression of the ΜΤΑ1 protein and the aforementioned factors regarding survival rate. Furthermore, we independently correlated the patient's survival in relation to whether they had undergone adjuvant chemotherapy or not. Results: It has been found to be low, moderate, or high expression of MTA1 levels in 48 out of 51 cancer tissues. Specifically, 49.0% of patients had low expression, 33.3% moderate, and 11.8% high expression of MTA1. Regarding the expression of MTA1 protein in correlation with various clinical and histopathological factors, a statistically significant correlation was observed with the degree of differentiation (p = 0.0068) and with the stage of the disease (p = 0.0173), but not with survival (p = 0.0740) or the age of them (p = 0.1547). Finally, it was found that overexpression of the MTA1protein is a prognostic factor for shorter survival in patients with pancreatic cancer (average 4.67 ± 0.95 months). Conclusions: MTA 1 protein may constitute an important prognostic marker in pancreatic cancer and could improve prognosis and treatment. [ABSTRACT FROM AUTHOR]

Background/Aims: Hepatic injury caused by ischemia/reperfusion (I/R) is a clinical problem associated with major liver surgery. Among other flavonoids, apigenin has shown a promising effect on I/R cases. In this study, we have investigated the effects of apigenin after liver I/R injury in rats. Materials and Methods: Forty eight rats were randomized into the following eight groups: (1) Control-sham group: rats subjected to the surgical procedure, except for liver I/R; (2) DMSO group: rats subjected to surgery, except for liver I/R given the apigenin solvent dimethyl-sulfoxide intraperitoneally; (3) C60 group; (4) C120 group; (5) C240 group: rats underwent liver ischemia for 45 min followed by reperfusion for 60 min, 120 min, and 240 min; (6) AP60 group; (7) AP120 group; (8) AP240 group: rats underwent liver ischemia for 45 min, and then given apigenin (5 mg) intraperitoneally followed by reperfusion for 60 min, 120 min, and 240 min. Reverse transcription polymerase chain reaction was performed on liver tissues to measure BCL-2/BAX expression, enzyme-linked immunosorbent assay to measure M30/M65 and ICAM-1. Immunohistochemistry was used to identify M30 biomarker in liver tissues. Statistical Analysis: Quantitative variables were tested by Kolmogorov--Smirnov test, repeated measures analysis of variance/Friedman test. Gene levels were assessed by Student's t-test/Mann--Whitney U-test. Results: BCL-2 levels were significantly higher in I/R apigenin groups than in I/R control groups. BAX levels were lower in the AP240 group than in C240 group. Prolongation of reperfusion resulted in increased activation of M30. ICAM-1 levels were lower in the AP240 group than in C240 group. Conclusions: Apigenin seems to inhibit the process of apoptosis and ameliorate the hepatic I/R injury. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: We studied the late angiogenic activity of free grafts and a pedicle flap in a rabbit urethroplasty model to determine whether angiogenic activity plays a role in late outcomes of urethral reconstruction in rabbits. Methods: Twenty-eight rabbits were randomly divided into five groups according to the method used to bridge a urethral defect as an onlay patch: Control, simple closure of urethral defect (Group O); free penile skin graft (FPSG, Group A); buccal mucosal graft (BuMG, Group B); bladder mucosal graft (BlMG, Group C); and pedicle penile skin flap (PPSF, Group D). Angiogenic activity of the patch on postoperative day 84 was assessed by immunohistochemistry. Results: The angiogenic activity in Groups O, A, B, C, and D was 23.33 ± 4.92 (means ± SD), 42.89 ± 6.52, 55.78 ± 3.46, 53.61 ± 6.17, and 24.11 ± 9.07 vessels per optical field, respectively. There were statistically significant differences ( p < .001) between Group O and A B, C, Group A and B, C, D, Groups B and D and Groups C and D, but not between Groups O and D ( p = 1.000) and Groups B and C ( p = .872). The long-term angiogenic activity of all the groups was significantly lower ( p < .001) than in the corresponding early groups. Conclusions: Although the angiogenic activity of all the groups decreased in the late assessment, the buccal mucosal graft continued to exhibit elevated angiogenesis above bladder or skin (free or pedicle) graft. Therefore, buccal mucosal patch graft might be preferable because of its easier harvesting. [ABSTRACT FROM AUTHOR]

The corticotropin-releasing hormone (CRH) system, consisting of CRH, urocortins (Ucns), their receptors CRH1 and CRH2, and CRH-binding protein, holds the principal role in mediating the response to stress stimuli. Besides their expression in the brain, CRH neuropeptides and receptors have been found in multiple peripheral sites. We investigated the expression of the CRH system in the human liver, using RT-PCR and immunohistochemistry. Ucn 1 gene transcripts were amplified in all the human liver biopsies examined. Ucn 1 immunoreactivity was localized in hepatocytes. CRH1 and CRH2(α) receptor gene expression was also found, and receptor protein had a similar distribution to Ucn 1. Finally, Ucn 1 and CRH receptor expression was demonstrated in hepatic biopsies from a variety of liver pathologies, including primary or metastatic liver carcinoma and cirrhosis. We conclude that the CRH system is expressed by human liver under normal and pathological conditions, Ucn 1 being the major ligand. Further study is required to unfold the biological role of these effectors in liver physiology and pathogenesis, as they may act in an autocrine manner through activation of the CRH receptors expressed locally. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Although the role of cholesterol absorption by the gallbladder epithelium in gallstone formation is well established, the exact process is poorly understood. Potential candidates for regulation of transepithelial cholesterol transport are suggested to be two large membrane multiple ligand receptors, megalin and cubilin. We studied the expression of these two proteins in both acalculous and calculous human gallbladder epithelia. Adult human gallbladder tissues were received from 21 patients (9 men, 12 women) who had undergone cholecystectomy. The patients were divided into two groups: group A (calculous gallbladder group; 5 men, 6 women; mean age 64.4 ± 11.1 years) with cholelithiasis, and group B (acalculous gallbladder group; 4 men, 6 women; mean age 55.3 ± 16.1 years). In the gallbladder tissues megalin and cubilin expression was studied by immunohistochemistry and conventional RT-PCR, and gene expression levels were estimated by real-time RT-PCR. Both megalin and cubilin gene transcripts were found in total RNA preparations from acalculous gallbladder. In contrast, in preparations from calculous gallbladder, none or only one of the proteins was detected. Immunoreactive proteins were detected in the simple columnar acalculous gallbladder epithelium but not in the calculous gallbladder epithelium. Our results show different expression patterns of the two proteins in calculous gallbladders and acalculous gallbladders. In the latter both proteins are expressed, suggesting an association with gallstone formation and implying a putative role of the two proteins in cholesterol endocytosis. In other words, the presence of both proteins may be essential for the prevention of stone formation. [ABSTRACT FROM AUTHOR]

Background: Improvement of the management of pancreatic cancer requires a better understanding of the genetic and molecular changes responsible for the development of the disease. The family of p21-activated kinases (PAKs) and especially PAK1 appears to mediate many cellular processes that contribute to the development and progression of pancreatic cancer, but the clinical relevance of PAK1 expression with the disease still remains unclear. Aim of the study was to assess the clinical value and the potential prognostic significance of PAK1 in pancreatic adenocarcinoma. Methods: We investigated the relationship between the PAK1 expression and the clinical and histopathologic characteristics of pancreatic cancer patients and the potential significance of PAK1 on survival. We examined tissue samples from 51 patients operated for pancreatic cancer. PAK1 expression was investigated with immunohistochemistry and correlated to clinicopathological parameters. Results: PAK1 was detected in all tumor samples and high expression was found in most patients. High PAK1 expression was also associated with younger age and well-differentiated tumors, but no association was found between PAK1 expression and Tumor-Node-Metastasis stage as well as deceased or alive status on follow-up. Moderate to high PAK1 expression favored higher 6-month and 1-year survival and low PAK1 expression 2-year survival but without statistical significance. Conclusions: Our results indicate that PAK1 could potentially be used as a prognostic marker in pancreatic cancer. Further studies could clarify whether utilization of PAK1 in therapeutic protocols for the treatment of pancreatic cancer will render them more effective. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]