Neither Isolated Hepatic Arterial Clamping nor Hepatic Arterial Ligation Induce Ischemic Type Biliary Lesions in Rats.

BACKGROUND Ischemic type biliary lesions (ITBL) is a troublesome complication after liver transplantation. Little is known about its pathogenesis and there is particularly little data about morphological alterations. Prolonged warm and cold ischemia time and reduced hepatic arterial perfusion are risk factors leading to ITBL. There are only a few animal models described in literature. Therefore, we examined the effects of 3 h of hepatic artery ischemia-reperfusion (3 h I/R) and hepatic arterial ligation (HAL), both combined with ligation of the peribiliary plexus (PBP). MATERIAL AND METHODS 3 h I/R was performed by clamping the hepatic artery with microvascular clamps for 3 h. HAL was performed by ligation of the hepatic artery. Both procedures were combined with stenting of the common bile duct with double ligation of the PBP. A sham group without clamping served as control. Serum activities of aspartate transaminase (AST) and alanine transaminase (ALT), direct and total bilirubin (DB/TB), and lactate dehydrogenase (LDH) were measured. Bile flow was analyzed and histological examinations of leukocyte infiltration (CAE), cell proliferation (PCNA), apoptotic cells (HE), and bile ducts morphology (CK7) were performed. Western blots of the vascular endothelial growth factor (VEGF) and caspase 3 were made to investigate vascular growth expression and apoptotic cell death. RESULTS 3 h I/R and HAL were associated with a significant hepatocellular injury and inflammation, shown through increased AST and ALT, leukocyte infiltration, and apoptotic cell death. An increase of bile ducts and a reduction of arteries/bile duct ratio after 30 days was observed in the 3 h I/R group and HAL, but no ITBL-typical bile duct necrosis, intrahepatic strictures, or dilatations of bile ducts occurred. CONCLUSIONS Morphological alterations in a rat animal model of 3 h I/R and HAL could be demonstrated. However, a model of intrahepatic biliary lesions could not be established through hepatic arterial ligation or through 3-h hepatic arterial ischemia and reperfusion.

MicroRNA target prediction: theory and practice.

The present study is one of the few that includes tissue samples in the evaluation of target prediction algorithms designed to detect microRNA (miRNA) sequences that might interact with particular messenger RNA (mRNA) sequences. Twelve different target prediction tools were used to find miRNA sequences that might interact with CCL20 gene expression. Different algorithms predicted controversial miRNA sequences for CCL20 regulation due to a different weighting of parameters. Hsa-miR-21 and hsa-miR-145 suggested by four or more programs were chosen for further investigation. Possible real interaction of these miRNA sequences with CCL20 gene expression was monitored using luciferase assays and expression analyses of tissue samples of colorectal adenocarcinoma by either qRT-PCR or ELISA. Folding status of seed-binding sites in complete mRNA and 3'UTR of CCL20 was predicted. Prediction of miRNA expression was attempted based on CCL20 expression data. Eight of the target prediction tools forecasted a role for hsa-miR-21 and four mentioned hsa-miR-145 in CCL20 gene regulation. Laboratory experimentation showed that CCL20 may serve as a target of hsa-miR-21 but not hsa-miR-145. Expression of the molecules resulted in no clear assertion. Folding of seed-binding sites was predicted to be relatively constant for the complete mRNA and 3'UTR. Predicting miRNA expression based on target gene expression was impossible. This might be attributable to the fact that effects of miRNA activity may oscillate between gene product repression and activation. Additional systematic studies are needed to address this issue.

Successful management of postoperative necrotizing pancreatitis after infrarenal abdominal aortic aneurysm repair.

We present a case of severe necrotizing pancreatitis that developed after elective repair of an abdominal aortic aneurysm. Surgeons are confronted in cases of postoperative acute pancreatitis with the dilemma of potential intraabdominal infection and the high risk of a subsequent infection of the retroperitoneal synthetic material. The therapeutic options range from a restrictive regime to radical necrosectomy and multivisceral resection.

Silver acetate coating promotes early vascularization of Dacron vascular grafts without inducing host tissue inflammation.

BACKGROUND: Silver acetate is frequently used as an antimicrobial coating of prosthetic vascular grafts. However, the effects of this coating on the early inflammatory and angiogenic host tissue response still remain elusive. Therefore, the aim of the present in vivo study was to analyze the biocompatibility and vascularization of silver acetate-coated and uncoated vascular grafts during the initial phase after implantation. METHODS: Two different prosthetic vascular grafts (ie, uncoated Dacron and silver acetate-coated Dacron Silver) were implanted into the dorsal skinfold chamber of C57BL/6 mice (n = 8 per group) to study angiogenesis and leukocytic inflammation at the implantation site by means of repetitive intravital fluorescence microscopy over a 14-day period. At the end of the in vivo experiments, collagen formation, apoptosis, and cell proliferation were analyzed in the newly developed granulation tissue surrounding the implants by histology and immunohistochemistry. RESULTS: During the initial 14 days after implantation, Dacron Silver exhibited an improved vascularization, as indicated by a significantly increased functional capillary density compared with Dacron. This was not associated with a stronger leukocytic inflammatory host tissue response to the implants. Moreover, silver acetate coating did not affect collagen formation, apoptosis, and cell proliferation at the implantation site. CONCLUSIONS: Silver acetate coating of prosthetic vascular grafts improves their early vascularization without inducing severe inflammatory side effects. Accordingly, this material modification crucially contributes to an improved incorporation of the implants into the host tissue, which may decrease the risk of vascular graft infection.

Torquated giant appendix epiploica mimicking intraperitoneal liposarcoma: report of a case.

A 49-year-old woman presented with acute abdominal pain in the right iliac fossa in our emergency department. Pain was abrupt in onset and severely colicky in nature. Abnormal laboratory values included a C-reactive protein of 75 mg/L and a CA-125 of 70.3 U/mL. White blood cell count was normal. Abdominal computed tomography (CT) scan revealed an inhomogeneous mass of 9.5 x 3.5 x 5.5 cm in diameter close to the appendix vermiformis and the sigmoid colon. Because of the clinical symptoms of an acute abdomen an explorative laparotomy was performed. Intraoperatively a pedunculated tumor beginning at the serosa of the sigmoid colon was found. The appendix was unremarkable. The macroscopic aspect as well as the backtable incision of the tumor was suspicious of an intraperitoneal liposarcoma. Rapid section and histopathologic examination revealed necrotic fat tissue without any malignancy. The patient was discharged from the hospital 7 days after the operation with normal laboratory parameters and without further complication. When epiploic appendagitis is evident as a big tumor mass in addition to clinical symptoms of an acute abdomen and elevated tumor markers, surgical exploration is mandatory.

Elevated Plasma C-reactive protein in chronically distressed subjects who carry the A allele of the TNF-alpha -308 G/A polymorphism.

OBJECTIVE: Sustained psychological stress may result in a state operationalized as "vital exhaustion." Exhaustion predicted coronary artery disease (CAD) events whereby increased inflammatory activity might mediate this link. Moreover, there is an emerging importance of gene-environmental interactions in CAD. We investigated the effect of exhaustion severity on plasma levels of C-reactive protein (CRP) and whether exhaustion might regulate CRP levels via the -308G/A polymorphism of the tumor necrosis factor (TNF)-alpha gene. METHODS: We assessed exhaustion in 275 industrial employees (mean age +/- SD, 41 +/- 9 years, 88% men) using the Maastricht Questionnaire. Subjects were stratified as per exhaustion severity: none (N = 80), moderate (N = 128), and severe (N = 67). The TNF-alpha polymorphism was determined by real-time polymerase chain reaction, and plasma CRP levels were measured by a high-sensitivity immunoassay. RESULTS: There was a significant interaction between exhaustion and the TNF-alpha polymorphism, explaining 4.5% in the variance of plasma CRP values (F(5,271) = 2.47, p =.033); the result held after controlling for classic cardiovascular risk factors. Adjusted mean CRP levels across exhaustion strata in GA (N = 70) and AA (N = 3) carriers combined were 0.91 mg/l (none), 1.78 mg/l (moderate), and 2.61 mg/l (severe) as compared with 1.24 mg/l, 1.61 mg/l, and 1.36 mg/l for the GG wild-type (N = 202). CONCLUSION: The findings suggest that the A allele of the TNF-alpha -308 G/A polymorphism may mediate inflammation with exhaustion in a dose-response relationship, while with the GG wild-type exhaustion severity seems unrelated to CRP levels. The finding provides a rationale for gene-environmental interactions by which psychosocial factors may promote atherosclerosis and CAD.