Upregulation of hepatic melanocortin 4 receptor during rat liver regeneration.

BACKGROUND: Melanocortin 4 receptor (MC4R) is predominantly recognized to mediate energy metabolism and anti-inflammation through the central nervous system. However, the expression of MC4R has recently been identified in rat liver and was shown to be upregulated during acute phase response. This study aims to investigate potential roles of MC4R in liver regeneration. MATERIALS AND METHODS: Rat partial hepatectomy (PH) was performed, and MC4R expression was analyzed at different time points after resection. Sham-operated animals (SH) served as controls. In vitro primary hepatocytes (HCs) were isolated from normal rat liver and stimulated with α-melanocyte-stimulating hormone (MC4R agonist). Real-time polymerase chain reaction, Western blot, and immunofluorescence staining were applied to detect gene expression. RESULTS: Up to 8 h after PH, hepatic messenger RNA of proinflammatory cytokines interleukin 6 and tumor necrosis factor α reached peak values. Between 8 and 72 h after PH, rat liver regeneration was extremely active as assessed by the regeneration indices labeled by Ki-67. Immunofluorescence staining indicated that MC4R was mostly expressed in hepatocyte nuclear factor 4(+) cells (HCs) and upregulated during rat liver regeneration. Concurrently, the expression of hepatic MC4R protein was significantly higher in PH than in SH animals, and phosphorylated extracellular signal-regulated kinase 1/2 was remarkably increased in PH compared with SH animals (P < 0.05, respectively). In vitro experiments showed that the expression of proliferating cell nuclear antigen was significantly higher in HCs treated with α-melanocyte-stimulating hormone than in control HCs, which was correlated to the increase of phosphorylated extracellular signal-regulated kinase 1/2 and reduction of phosphorylated signal transducer and activator of transcription 3 (P < 0.05, respectively). CONCLUSIONS: MC4R is predominantly expressed in HCs and upregulated during rat liver regeneration. In vitro stimulation of HC MC4R is associated with a modulation of extracellular signal-regulated kinase and signal transducer and activator of transcription 3 pathways regulating liver regeneration.

Amiodarone pretreatment of organ donors exerts anti-oxidative protection but induces excretory dysfunction in liver preservation and reperfusion.

The continuous shortage of organs necessitates the use of marginal organs from donors with various diseases, including arrhythmia-associated cardiac failure. One of the most frequently used anti-arrhythmic drugs is amiodarone (AM), which is given in particular in emergency situations. Apart from its anti-arrhythmic actions, AM provides anti-oxidative properties in cardiomyocytes. Thus, we were interested in whether AM donor pretreatment affects the organ quality and function of livers procured for preservation and transplantation. Donor rats were pretreated with AM (5 mg/kg of body weight) 10 minutes before flush-out of the liver with a cold (4 degrees C) histidine-tryptophan-ketoglutarate solution (n = 8). Livers were then stored for 24 hours at 4 degrees C before ex situ reperfusion with a 37 degrees C Krebs-Henseleit solution for 60 minutes in a nonrecirculating system. At the end of reperfusion, tissue samples were taken for histology and Western blot analysis. Animals with vehicle only (0.9% NaCl) served as ischemia/reperfusion controls (n = 8). Additionally, livers of untreated animals (n = 8) not subjected to 24 hours of cold ischemia served as sham controls. AM pretreatment effectively attenuated lipid peroxidation, stress protein expression, and apoptotic cell death. This was indicated by an AM-mediated reduction of malondialdehyde, heme oxygenase-1, and caspase-3 activation. However, AM treatment also induced mitochondrial damage and hepatocellular excretory dysfunction, as indicated by a significantly increased glutamate dehydrogenase concentration in the effluate and decreased bile production. In conclusion, AM donor pretreatment exerts anti-oxidative actions in liver preservation and reperfusion. However, these protective AM actions are counteracted by an induction of mitochondrial damage and hepatocellular dysfunction. Accordingly, AM pretreatment of donors for anti-arrhythmic therapy should be performed with caution.

Hepatocellular carcinoma: Surgeon's view on latest findings and future perspectives.

Hepatocellular carcinoma (HCC) is the most common liver-derived malignancy with a high fatality rate. Risk factors for the development of HCC have been identified and are clearly described. However, due to the lack of tumor-specific symptoms, HCC are diagnosed at progressed tumor stages in most patients, and thus curative therapeutic options are limited. The focus of this review is on surgical therapeutic options which can be offered to patients with HCC with special regard to recent findings, not exclusively focused on surgical therapy, but also to other treatment modalities. Further, potential promising future perspectives for the treatment of HCC are discussed.

Surgical-site infection after abdominal wall closure with triclosan-impregnated polydioxanone sutures: results of a randomized clinical pathway facilitated trial (NCT00998907).

BACKGROUND: Wound infections after abdominal surgery are still frequent types of nosocomial infections. Suture materials might serve as a vehicle for mechanical transport of bacteria into the surgical wound. To prevent the contamination of suture material in surgical wounds, triclosan-coated suture materials with antibacterial activity was developed. We here report a prospective randomized pathway controlled trial investigating the effect of triclosan impregnation of polydioxanone sutures used for abdominal wall closure on the rate of surgical-site infections. PATIENTS AND METHODS: A total of 856 patients included in this trial underwent a standardized clinical pathway documented abdominal wall closure after abdominal surgery. Patients were randomized to have the fascia closed with either a 2-0 polydioxanone loop or a triclosan impregnated 2-0 polydioxanone loop. The primary outcome was the number of wound infections. Risk factors for poor wound healing were collected prospectively to compare the two groups. RESULTS: When a PDS loop suture for abdominal wall closure was used, 42 (11.3%) patients with wound infections were detected. The number of patients with wound infections decreased significantly to 31 when the PDS plus for abdominal wall closure was used (6.4%, P < .05). Other risk factors for the development of side infections were comparably in the two groups. CONCLUSION: This clinical pathway facilitated trial shows that triclosan impregnation of a 2-0 polydioxanone closing suture can decrease wound infections in patients having a laparotomy for general and abdominal vascular procedures.

Incisional hernia after abdominal closure with slowly absorbable versus fast absorbable, antibacterial-coated sutures.

BACKGROUND: Incisional hernia remains among the most common complications after midline incision of the abdominal wall. The role of the suture material used for abdominal wall closure remains controversial. To decrease bacterial adherence to surgical sutures, braided suture materials with antibacterial activity (Vicryl plus, Ethicon, Inc) were developed. This is the first study to analyze long-term results using an antibacterial-braided suture material for abdominal wall closure in a large clinical trial. METHODS: To analyze the effects of Triclosan-coated suture material (Vicryl plus) on the development of incisional hernia, we performed a 36-month follow-up of 1,018 patients who had a primary midline incision for elective abdominal surgery. In the first time period, a PDS II loop suture was used. In the second observation period, we used Vicryl plus. All variables were recorded prospectively in a database. The primary outcome was the number of incisional hernias. Risk factors for the development of incisional hernias were collected prospectively to compare the 2 groups. RESULTS: The overall incisional hernia rate in the 36-month follow-up period was 14.6%. Analyzing the influence of the suture material used on the development of incisional hernia, we did not find differences between the 2 groups (PDS II, 14%; Vicryl plus, 15.2%). In the multivariate analysis of possible factors in the study population, only body mass index (BMI) showed a significant influence on the development of incisional hernias. Despite the incidence of wound infections being less in the Vicryl plus group (6.1% vs 11.9%; P < .05), there were no difference in incidence of incisional hernia between the 2 groups. CONCLUSION: Fast absorbable sutures with antibacterial coating (Tricosan) do not increase the hernia rate after midline abdominal incision compared with slowly absorbable sutures, when wound infection rates are decreased by coating the fast absorbable suture with Triclosan. The development of incisional hernia is significantly increasing in patients with a BMI >30 kg/m(2).