Effect of cyclosporine on oxidative phosphorylation and adenylate energy charge of regenerating rat liver

The effect of cyclosporin A (CyA) on regenerating liver was investigated in subtotal hepatectomized rats treated with CyA in terms of mitochondrial phosphorylative activity, hepatic energy charge, and serum bilirubin levels. In the CyA-treated hepatectomized group, the energy charge decreased from normal control value of 0.857 to 0.782 at 6 h after hepatectomy. The decreased energy charge, however, gradually increased and returned to 0.842 at 48 h after hepatectomy with no significant changes being observed between CyA-treated and untreated hepatectomized groups. Phosphorylation rate in the CyA-untreated group increased to 142% of the normal control at 24 h and then decreased to 114% at 48 h after hepatectomy. By contrast, phosphorylation rate in the CyA-treated group increased to 144% of the normal control at 24 h, but remained at the high value of 132% (P less than 0.01; compared to the CyA-untreated group) even at 48 h after hepatectomy. Serum total bilirubin levels in the CyA-treated group were significantly higher than those in the CyA-untreated group during all experimental periods. We conclude that CyA does not exert a direct detrimental effect on mitochondrial function and that, despite the marked hyperbilirubinemia induced by CyA, the mitochondrial phosphorylative activity increases adaptively to provide sufficient energy for enhanced ATP-utilizing reactions in an early process of liver regeneration.     

Relationship between initial hepatic uptake of indocyanine green and hepatic energy status in hepatectomized rabbits

The relationship between initial hepatic uptake of indocyanine green (ICG) and hepatic energy status was studied in about 70% hepatectomized rabbits. At 24 h after hepatectomy, the initial plasma disappearance rate (K) and the maximal removal rate (Rmax) of ICG fell to 27 and 26%, respectively, and the mitochondrial phosphorylative activity was enhanced maximally with a concomitant decrease in the energy charge ( (ATP+1/2ADP)/(ATP+ADP+AMP) ) level. Afterward, the initial reduction of ICG removal rate was followed by a rapid increase in week 1 and more gradual return to preoperative values by week 6 after hepatectomy. In the early period after hepatectomy (1-7 days), the mitochondrial phosphorylative activity was the higher the smaller the %K value was, while in the late period after hepatectomy (1-6 weeks), the mitochondrial phosphorylative activity remained unchanged irrespective of increasing %K. It is suggested that the mitochondrial phosphorylative activity may be a better guide to evaluate the functional status of the remnant liver than the initial hepatic uptake of ICG, especially in the early period after hepatoctomy.     

Superficial Surgical Site Infection in Hepatobiliary-Pancreatic Surgery: Subcuticular Suture Versus Skin Staples

Purpose

Postoperative superficial surgical site infection is a major complication in hepatobiliary-pancreatic surgery. We aimed to compare the efficacy of subcuticular sutures versus staples for skin closure in preventing superficial surgical site infection in hepatobiliary-pancreatic surgery.

Methods

Consecutive patients who underwent hepatobiliary-pancreatic surgery at our hospital from October 2006 to March 2011 and from April 2012 to March 2015 were reviewed retrospectively. Superficial surgical site infection incidence was evaluated in patients who received subcuticular sutures and those who received staples for skin closure. Propensity score matching analysis was used to adjust bias from confounding factors.

Results

A total of 691 patients were included. Patients with skin staple closures (n?=?346) were compared with patients with subcuticular suture closures (n?=?345). After a propensity score matching analysis, a significant difference in superficial surgical site infection incidence was found between the skin stapler group (11.3%) and subcuticular sutures group (2.6%). The same comparison was performed by a subgroup analysis and supported this finding in patients after hepatectomy without biliary reconstruction, pancreatoduodenectomy, or open laparotomy surgeries and in patients with body mass index <?25.

Conclusions

Subcuticular suturing after hepatobiliary-pancreatic surgery was more efficacious in reducing postoperative superficial surgical site infection incidence than staples for skin closure.

     

Variation in the attachment of <Emphasis Type="Italic">Streptococcus pneumoniae</Emphasis> to human pharyngeal epithelial cells after treatment with S-carboxymethylcysteine

S-carboxymethylcysteine (S-CMC) is a mucolytic agent that can prevent respiratory infection by decreasing the attachment of respiratory pathogens to human pharyngeal epithelial cells (HPECs). Streptococcus pneumoniae is a major cause of respiratory infections. A previous study revealed that treatment of S. pneumoniae with S-CMC caused a decrease in the attachment of this bacterium to HPECs. In the present study we found that the effect of S-CMC varied according to hosts and strains. S-CMC treatment altered the surface structure of S. pneumoniae, resulting in a decrease of attachment, without affecting the virulence of the bacteria.     

A histone deacetylase inhibitor enhances recombinant adeno-associated virus-mediated gene expression in tumor cells.

The transduction of cancer cells using recombinant adeno-associated virus (rAAV) occurs with low efficiency, which limits its utility in cancer gene therapy. We have previously sought to enhance rAAV-mediated transduction of cancer cells by applying DNA-damaging stresses. In this study, we examined the effects of the histone deacetylase inhibitor FR901228 on tumor transduction mediated by rAAV types 2 and 5. FR901228 treatment significantly improved the expression of the transgene in four cancer cell lines. The cell surface levels of alpha v integrin, FGF-R1, and PDGF-R were modestly enhanced by the presence of FR901228. These results suggest that the superior transduction induced by the HDAC inhibitor was due to an enhancement of transgene expression rather than increased viral entry. Furthermore, we characterized the association of the acetylated histone H3 in the episomal AAV vector genome by using the chromatin immunoprecipitation assay. The results suggest that the superior transduction may be related to the proposed histone-associated chromatin form of the rAAV concatemer in transduced cells. In the analysis with subcutaneous tumor models, strong enhancement of the transgene expression as well as therapeutic effect was confirmed in vivo. The use of this HDAC inhibitor may enhance the utility of rAAV-mediated transduction strategies for cancer gene therapy.