PPARγ activation following apoptotic cell instillation promotes resolution of lung inflammation and fibrosis via regulation of efferocytosis and proresolving cytokines.

Changes in macrophage phenotype have been implicated in apoptotic cell-mediated immune modulation via induction of peroxisome proliferator-activated receptor-γ (PPARγ). In this study, we characterized PPARγ induction by apoptotic cell instillation over the course of bleomycin-induced lung injury in C57BL/6 mice. Next, the role of PPARγ activation in resolving lung inflammation and fibrosis was investigated. Our data demonstrate that apoptotic cell instillation after bleomycin results in immediate and prolonged enhancement of PPARγ mRNA and protein in alveolar macrophages and lung. Moreover, PPARγ activity and expression of its target molecules, including CD36, macrophage mannose receptor, and arginase 1, were persistently enhanced following apoptotic cell instillation. Coadministration of the PPARγ antagonist, GW9662, reversed the enhanced efferocytosis, and the reduced proinflammatory cytokine expression, neutrophil recruitment, myeloperoxidase activity, hydroxyproline contents, and fibrosis markers, including type 1 collagen α2, fibronectin and α-smooth muscle actin (α-SMA), in the lung by apoptotic cell instillation. In addition, inhibition of PPARγ activity reversed the expression of transforming growth factor-ß (TGF-ß), interleukin (IL)-10, and hepatocyte growth factor (HGF). These findings indicate that one-time apoptotic cell instillation contributes to anti-inflammatory and antifibrotic responses via upregulation of PPARγ expression and subsequent activation, leading to regulation of efferocytosis and production of proresolving cytokines.

Preoperative inflammation is a prognostic factor for gallbladder carcinoma.

BACKGROUND: Inflammation frequently accompanies gallbladder carcinoma (GBC), but its impact on outcome is unclear. The present study investigated the impact of concomitant inflammation on survival of patients with GBC. METHODS: All patients undergoing surgery for GBC between October 2003 and May 2009 were identified retrospectively from a prospectively collected database. Patients were classified according to whether preoperative inflammation was present (65 patients) or not (23). RESULTS: A total of 88 patients were enrolled. There were no differences in sex, mean age, tumour node metastasis (TNM) stage and radicality of resection between the two groups. The overall 3-year survival rate was lower in patients with preoperative inflammation than in those without (33 versus 73 per cent; P = 0·001). In univariable analysis, preoperative inflammation, T, N and M category, TNM stage, radicality of surgery and tumour differentiation were significant prognostic factors. The presence of preoperative inflammation (hazard ratio (HR) 2·38, 95 per cent confidence interval 1·04 to 5·43), lymph node metastases (HR 5·23, 1·05 to 26·09) and R1 or R2 resection (HR 3·77, 1·47 to 9·72) were independent prognostic factors for poor survival. CONCLUSION: The presence of preoperative inflammation is an independent prognostic factor for poor survival in patients with GBC.

Patency of splenic vessels after laparoscopic spleen and splenic vessel-preserving distal pancreatectomy.

BACKGROUND: This study evaluated the short- and long-term patency of preserved splenic vessels after laparoscopic spleen-preserving distal pancreatectomy (SPDP) with preservation of the splenic vessels. METHODS: This single-centre retrospective study included all patients who had undergone splenic vessel-preserving laparoscopic SPDP between 2004 and 2007. The patency of the splenic vessels was assessed by abdominal computed tomography and classified into three grades according to the degree of stenosis. RESULTS: Twenty-two patients were included. The preoperative patency of the splenic artery and vein was normal in 20 and 19 patients respectively. Normal patency of the splenic artery and vein was observed in 16 and five patients respectively within 1 month of surgery, and in 19 and nine patients 6 months or more after operation. Nine of ten patients with complete splenic vein occlusion developed a collateral circulation in the late postoperative phase. Splenic perfusion was well preserved in all patients. CONCLUSION: Splenic vessel-preserving laparoscopic SPDP has the short-term benefit of good perfusion to the spleen. In the long term, there is a risk of left-sided portal hypertension if the splenic vein becomes occluded after surgery. (c) 2009 British Journal of Surgery Society Ltd.

Clinical outcomes compared between laparoscopic and open distal pancreatectomy.

BACKGROUND: Laparoscopic surgery for pancreatic disease has gained increasing popularity. A laparoscopic distal pancreatectomy is technically simple and has been adopted as the preferred method in many centers. However, there is limited information on the outcomes of the laparoscopic surgery compared with open surgery. Therefore, this study aimed to investigate the clinical outcomes of laparoscopic distal pancreatectomy and to evaluate its efficacy compared with open distal pancreatectomy. METHODS: From February 1995 to March 2006, 31 patients underwent laparoscopic distal pancreatectomy, and 167 patients underwent open distal pancreatectomy at Seoul National University Hospital and Bundang Seoul National University Hospital. A case-control design was used with 2:1 matching to compare laparoscopic surgery with open surgery. Among 167 patients who underwent open distal pancreatectomy, 62 patients whose age, gender, and pathology were similar to those of patients who underwent laparoscopic surgery were selected for this study. The operation time, intraoperative transfusion requirements, duration of postoperative hospitalization, complications, mortality, recurrence, and hospital charges were analyzed. RESULTS: There were no significant differences in operation time, rate of intraoperative transfusions, complications, recurrence, or mortality between the two groups. Laparoscopic distal pancreatectomy was associated with a statistically significant shorter hospital stay (11.5 days vs 13.5 days; p = 0.049), but with more expensive hospital charges than open distal pancreatectomy (p < 0.01). CONCLUSION: Laparoscopic distal pancreatectomy is a clinically safe and effective procedure for benign and borderline pancreatic tumors.

Totally laparoscopic management of choledochal cysts using a four-hole method.

BACKGROUND: Choledochal cyst is a rare benign disease of the biliary tract. However, once diagnosed, it must be excised with the gallbladder because of the risk for cancer developing in the biliary tree, including the gallbladder. This report introduces a new surgical technique for totally laparoscopic excision of choledochal cyst and hepaticojejunostomy using a four-hole method. METHODS: Between October 2003 and May 2005, the authors performed totally laparoscopic choledochal cyst excision for 12 patients. All the patients except one were women, and the mean age was 37.3 years (range, 17-62 years). According to the Todani classification, there were five type Ia cases, four type Ic cases, and three type IV cases. Choledochal cyst excision and Roux-en-Y hepaticojejunostomy were performed laparoscopically using the four-port technique. RESULTS: The mean operation time was 228 min (range, 150-330 min). No operative or postoperative transfusion was required. An oral diet was started on postoperative day 3. The average length of hospital stay was 5.8 days. There was no major complication associated with anastomosis leakage or obstruction. No patient had an adverse response, as determined by clinical or laboratory evaluation during a 2- to 19-month follow-up period. CONCLUSIONS: Considering that choledochal cyst is common among young women, who are especially interested in cosmetic results in addition to complete resolution of medical problems, the laparoscopic management of choledochal cyst may be an attractive treatment option.

Mitochondria are impaired in the adipocytes of type 2 diabetic mice.

AIMS/HYPOTHESIS: The aim of this study was to confirm a link between mitochondrial dysfunction and type 2 diabetes. MATERIALS AND METHODS: Cellular levels of mitochondrial proteins, cellular mitochondrial DNA content, and mitochondrial function and morphology were assessed by MitoTracker staining and electron microscopy, in white adipose tissue of 12-week-old male wild-type, obese (ob/ob), and diabetic (db/db) mice. RESULTS: Levels of mitochondrial proteins were found to be very similar in the livers and muscles of all the mice studied. However, levels were greatly decreased in the adipocytes of db/db mice, but not in those of the wild-type and ob/ob mice. Levels of mitochondrial DNA were also found to be considerably reduced in the adipocytes of db/db mice. MitoTracker staining and under electron microscopy revealed that the number of mitochondria was reduced in adipocytes of db/db mice. Respiration and fatty acid oxidation studies indicated mitochondrial dysfunction in adipocytes of db/db mice. Interestingly, there was an increase in mitochondria and mitochondrial protein production in adipocytes of db/db mice treated with rosiglitazone, an agent that enhances insulin sensitivity. CONCLUSIONS/INTERPRETATION: Taken together, these data indicate that mitochondrial loss in adipose tissue is correlated with the development of type 2 diabetes.

Immunohistochemical localization of substance P, calcitonin gene-related peptide, galanin and calcium-binding proteins in trigeminal ganglia of goat (Capra hircus).

The objectives of this study was to provide a quantitative analysis of calcium-binding proteins, calbindin (CB), parvalbumin (PA), substance P (SP), calcitonin gene-related peptide (CGRP) and galanin (GAL), in trigeminal ganglia of goats, to establish whether they exhibit coexistence relationships between each other, and to examine possible colocalization with SP, CGRP and GAL, which have been well characterized according to their distributions in an abundance of large and/or small neurones. CB (12.78%), PA (31.91%), SP (24.63%), CGRP (44.44%) and GAL (3.29%) immunoreactive (IR) cells were observed. About 38.37, 8.7 and 0.73% of CGRP-IR neurones in the trigeminal ganglion were also immunoreacted with SP, GAL and CB, respectively. Almost all SP-IR cells are labelled with CGRP (approximately 92.52%), whereas only 16.02 and 0.44% of SP-IR neurones colocalized with GAL and CB. Approximately 4.65 and 1.10% of the CB-IR cells were found to contain CGRP and SP immunoreactivity, respectively. Conversely, no CB-IR cell exhibited GAL immunoreactivity. In addition, all the GAL-IR cells showed CGRP and SP immunoreactivity. The number of CB-, PA-, SP-, CGRP- and GAL-IR neurones in goat trigeminal ganglion are abundant than that of other animals. These results elucidate that the goat differs from other mammalian species in the distribution and localization of neurochemical substances in trigeminal ganglia, and suggest that this difference may be relevant to the morphological characteristics of cerebral vasculatures such as epidural rete mirabile of goat.