Effect of phlorotannins on myofibroblast differentiation and ECM protein expression in transforming growth factor ß1­induced nasal polyp­derived fibroblasts.

Phlorotannins (PTNs), a group of phenolic compounds from seaweeds, have diverse bioactivities. However, there has been no report on their antifibrotic effects during nasal polyp (NP) formation. In the present study, the effect of PTNs on transforming growth factor (TGF)­ß1­induced profibrotic responses in nasal polyp­derived fibroblasts (NPDFs) were determined and the relevant signaling pathways were investigated. The expression levels of collagen type­1 (Col­1) and fibronectin in NP tissues were measured by western blot analysis and immunohistochemistry. The NPDFs were treated with TGF­ß1 (1 ng/ml) in the presence or absence of PTNs (5­30 µg/ml). The expression levels of α­smooth muscle actin (α­SMA), Col­1, fibronectin, and phosphorylated­small mothers against decapentaplegic (Smad)2/3 in NPDFs were measured by western blot analysis. The contractile activity of the NPDFs was determined by a collagen gel contraction assay. Col­1 and fibronectin proteins were found to be expressed in NP tissues. PTNs had no significant cytotoxic effect on TGF­ß1­induced NPDFs. TGF­ß1 induced the expression α­SMA, Col­1 and fibronectin, and stimulated fibroblast­mediated contraction of collagen gel. However, pre­treatment with PTNs inhibited the expression of these proteins. The inhibitory effects were mediated through the suppression of Smad2/3 signaling pathways in TGF­ß1­induced NPDFs. These resulted suggested that PTNs may be important in inhibiting myofibroblast differentiation and extracellular matrix protein accumulation in NP formation through the Smad2/3 signaling pathway.

Anti-Inflammatory Potential of Carpomitra costata Ethanolic Extracts via Inhibition of NF-κB and AP-1 Activation in LPS-Stimulated RAW264.7 Macrophages.

Marine algae have valuable health and dietary benefits. The present study aimed to investigate whether an ethanol extract of Carpomitra costata (CCE) could inhibit the inflammatory response to LPS. CCE attenuated the production of proinflammatory mediators, such as prostaglandin E2 (PGE2) and nitric oxide (NO), by inhibiting inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-induced RAW264.7 macrophages. CCE also inhibited the expression of proinflammatory cytokines such as IL-1ß, TNF-α, and IL-6. CCE suppressed the LPS-induced DNA-binding activity of (NF-κB) and activator protein-1 (AP-1). In addition, CCE attenuated the LPS-stimulated phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK) and phosphatidylinositol 3'-kinase/Akt (PI3K/Akt). Functional aspects of the JNK and Akt signaling pathways were analyzed using specific inhibitors, which attenuated the LPS-induced production of proinflammatory cytokines, and NO and PGE2 expression by suppressing AP-1 and NF-κB activity. In particular, the AP-1 signaling pathway is not involved in the production of inflammatory cytokines, such as IL-6, TNF-α, and IL-1ß. These results suggested that CCE might exert its anti-inflammatory action by downregulating transcriptional factors (NF-κB and AP-1) through JNK and Akt signaling pathways. The current study suggested that CCE might be a valuable candidate for the treatment of inflammatory disorders.

Prevention of hepatitis B recurrence after living donor liver transplantation: primary high-dose hepatitis B immunoglobulin monotherapy and rescue antiviral therapy.

The prevention of hepatitis B virus (HBV) recurrence is essential after liver transplantation in patients infected with HBV. We evaluated the efficacy of primary high-dose hepatitis B immunoglobulin (HBIG) monotherapy and rescue antiviral therapy in 639 HBV-infected adult patients who underwent living donor liver transplantation (LDLT) between February 1997 and December 2004. The overall 5-year survival rate was 80.7%, and recurrence of hepatocellular carcinoma was the most common cause of late mortality. Pretransplant HBV replication was observed in 392 (61.3%) patients. The interval of 10,000-IU HBIG administration to maintain antibody to hepatitis B surface antigen > 500 IU/L was 30 days in 11.4% patients, 40 to 50 days in 72.1%, and 60 days in 16.5%. At the last follow-up, 3.9% of the patients without HBV recurrence were receiving combination therapy. Overall 1-year, 3-year, 5-year, and 10-year HBV recurrence rates were 1.4%, 5.5%, 7.3%, and 8.5%, respectively. HBV recurrence occurred after a mean of 25.7 +/- 16.4 months after LDLT. After HBV recurrence, 5 of 9 patients died from rapidly progressive liver failure before treatment with adefovir, and only 1 of 29 patients died after treatment with adefovir. Need for frequent HBIG infusions (< or =30 days), active pretransplant HBV replication, and hepatocellular carcinoma recurrence were significant risk factors for HBV recurrence and indications for combination therapy. Our posttransplant HBV prophylaxis regimen resulted in a 5-year HBV recurrence rate of 7.3% and a mortality rate of 13.2% after HBV recurrence, showing the effectiveness of high-dose HBIG monotherapy and rescue antiviral therapy.

Radical surgical resection for carcinoid tumors of the ampulla.

Ampullary carcinoid tumors are extremely rare. The present study describes the clinicopathological features and outcomes for 10 ampullary carcinoid patients who underwent radical resection from 1998 to 2005. During this study period, 294 patients underwent pancreatoduodenectomy for ampullary neoplasms in our institution. The mean patient age was 58.0 +/- 13.4 years, and seven were male. Initial clinical manifestations were jaundice in four patients, nonspecific gastrointestinal symptoms in five, and completely asymptomatic in one. Standard pancreatoduodenectomy was performed in three patients, and pylorus-preserving pancreatoduodenectomy in seven, and there were no major complications. The mean tumor size and volume were 2.1 +/- 1.3 cm and 4.1 +/- 6.9 ml, respectively. Synaptophysin staining was positive in ten patients and chromogranin staining positive in eight. R0 resection was achieved in all ten patients. Overall and disease-free survival rates were 90 and 80% at 1 year, and 64 and 56% at 3 years, respectively. The liver was the most common site of initial metastasis after curative resection. Univariate analyses revealed that a maximal tumor diameter > or =2 cm and tumor extension beyond the ampulla were risk factors for tumor recurrence. In conclusion, while the majority of ampullary carcinoids are indolent, this tumor is associated with a relatively poor prognosis. We believe that radical resection, with the aim of complete tumor removal and cure, is the treatment of choice.

Portal vein interposition using homologous iliac vein graft during extensive resection for hilar bile duct cancer.

Although autologous vein grafts have been used for portal vein (PV) reconstruction after long-segment portal vein resection during surgery for hilar bile duct cancer, their procurement prolongs operation time and increases morbidity. Less is known regarding the use of homologous vein grafts. The feasibility of homografts for PV reconstruction was preliminarily evaluated in two patients who underwent curative resection for hilar cholangiocarcinoma. Both patients underwent left lobectomy, caudate lobectomy, bile duct resection, and segmental PV resection and interposition vein graft reconstruction. The iliac vein homografts were obtained from deceased organ donors and stored for 1-2 days in cold preservation solution without freezing. Neither immunosuppression nor anticoagulation was attempted. One patient has shown good PV patency for 27 months. The second patient, who had received adjuvant chemoradiotherapy, showed an asymptomatic waisting at the proximal PV anastomosis site after 4 months, which was relieved by percutaneous balloon dilatation, and has been doing well for 12 months. In conclusion, our preliminary experience with these two patients suggests that cold-stored iliac vein homografts can be considered as PV substitutes after long PV segment resection during extensive hepatobiliary surgery.