Biliary complications after a right-lobe living donor liver transplantation

Right-lobe living donor liver transplantation (RL-LDLT) has become an acceptable procedure for adult patients with end-stage liver disease in this decade. However, biliary complications in RL-LDLT remain a serious problem: the incidence of anastomotic biliary leakage and stricture after RL-LDLT is reported to be 4.7%–18.2% and 8.3%–31.7%, respectively. The incidence varies according to the type of biliary reconstructions between Roux-en-Y hepaticojejunostomy and duct-to-duct biliary reconstruction. The anatomical biliary diversity of a right-lobe graft makes it difficult to reconstruct the biliary system. Indeed, most biliary strictures in patients with duct-to-duct reconstruction develop in multibranched fashion. In this regard, endoscopic biliary stenting appears to be efficacious for treating multibranched biliary strictures because multiple stenting permits the drainage of each segmental branch of the stricture. In this review, we describe various aspects of biliary complications occurring in RL-LDLT and their treatment.     

Effects of α-tocopherol on thiobarbituric acid reactive substances in serum and hepatic subcellular organelles and lipid metabolism

Thiobarbituric acid reactive substances (TBARS) increased in hepatic microsome fractions from rats aged 3 months as compared with such fractions from 1-month-old rats, though serum TBARS concentration did not differ between groups. Serum TBARS concentrations became significantly higher in adult rats aged 6–7 and 12–13 months than in those month old. TBARS reactions in mitochondria did not show such clear age-related change.Administration of a diet containing 0·5 per cent tocopherol to rats for 1–3 months, lowered the TBARS concentrations in microsomes concomitantly with a decrease of serum TBARS concentrations. In these rats, synthetic activities of cholesterol and fatty acid in the hepatic microsomes from acetate or mevalonate were similar in both treated and non-treated control groups. However, the activity was higher in the treated group than in the non-treated control after long-term (up to 6 months) feeding of tocopherol. Serum cholesterol, phospholipid and triglyceride concentrations in rats treated with tocopherol for 6 months were significantly lower than those in control rats.     

Up‐regulation of Rac1 in the bronchial smooth muscle of murine experimental asthma

There has been considerable research on the involvement of RhoA/Rho kinase signalling in smooth muscle contractions. However, only a few reports have addressed the specific role of Rac1, which is a member of the Rho GTPase superfamily. Therefore, this study investigated the role of Rac1‐related pathways in bronchial smooth muscle (BSM) contractions. Bronchial rings isolated from mice were suspended in an organ bath, and the isometric contractions of circular smooth muscles were monitored. The phosphorylation of myosin light chains (MLCs) was analysed by immunoblotting. The Rac1 inhibitor EHT1864 inhibited carbachol (CCh)‐induced BSM contractions, although high K⁺ depolarization‐induced BSM contractions were not significantly attenuated by EHT1864. Moreover, high K⁺‐ and phorbol 12,13‐dibutyrate (PDBu; PKC activator)‐induced contractions were not attenuated by Rac1 inhibition, whereas sodium fluoride (NaF)‐induced force development was inhibited by EHT1864. The gene and protein expression of Rac1 was increased in the BSM of a murine model with antigen‐induced airway hyper‐responsiveness (AHR). In addition, an increased force of the BSM contractions in AHR was suppressed by EHT1864 treatment, suggesting that the up‐regulation of Rac1 is involved in AHR. These findings suggest that an increase in Rac1‐mediated signalling is involved in the augmented contractions of BSMs in antigen‐induced AHR mice.     

Inflammation-associated cancer development in digestive organs: mechanisms and roles for genetic and epigenetic modulation

Chronic inflammation, regardless of infectious agents, plays important roles in the development of various cancers, particularly in digestive organs, including Helicobacter pylori-associated gastric cancer, hepatitis C virus-positive hepatocellular carcinoma, and colitis-associated colon cancers. Cancer development is characterized by stepwise accumulation of genetic and epigenetic alterations of various proto-oncogenes and tumor-suppressor genes. During chronic inflammation, infectious agents such as H pylori and hepatitis C virus as well as intrinsic mediators of inflammatory responses, including proinflammatory cytokines and reactive oxygen and nitrogen species, can induce genetic and epigenetic changes, including point mutations, deletions, duplications, recombinations, and methylation of various tumor-related genes through various mechanisms. Furthermore, inflammation also modulates the expressions of microRNAs that influence the production of several tumor-related messenger RNAs or proteins. These molecular events induced by chronic inflammation work in concert to alter important pathways involved in normal cellular function, and hence accelerate inflammation-associated cancer development. Among these, recent studies highlighted an important role of activation-induced cytidine deaminase, a nucleotide-editing enzyme essential for somatic hypermutation and class-switch recombination of the immunoglobulin gene, as a genomic modulator in inflammation-associated cancer development.