Metabolism of fatty acids and bile acids in plasma is associated with overactive bladder in males: potential biomarkers and targets for novel treatments in a metabolomics analysis

International Urology and Nephrology - The present study was conducted to identify metabolites using a metabolomics approach and investigate the relationship between these metabolites and urgency...     

Multiple Hepatic Vein Reconstruction Using an All-in-one Sleeve Patch Graft Technique in Living Donor Liver Transplantation: A Case Report

Maintaining hepatic inflow and appropriate venous drainage is important for maximizing the capacity of the retrieved graft in liver transplantation. Here, we report a successful case of multiple hepatic vein (HV) reconstruction using an all-in-one sleeve patch graft of the autologous great saphenous vein to ensure adequate blood flow through the HV. A patient with hepatocellular carcinoma caused by hepatitis C virus–induced cirrhosis underwent living donor liver transplantation using a right lobe graft. A preoperative dynamic computed tomography scan and intraoperative findings revealed that the graft had three middle HV tributaries, a superficial vein, segment VIII HV (V8), and segment V HV (V5). The openings of the superficial vein and V8 were located very close to that of the right hepatic vein (RHV) in the cutting surface. Each HV had significant diameter and drainage territory requiring reconstruction. An autologous great saphenous vein was used to create a sleeve patch to incorporate the close-packed HV openings. The autologous sleeve patch graft was sutured to the openings of the RHV and the superficial vein and the hole created on the sleeve patch graft was anastomosed to the openings of V8 directly on the back table to create an all-in-one sleeve patch. For the V5 reconstruction, the recipient's intrahepatic portal vein graft was used to create an interpositional conduit from the recipient's V5 to the inferior vena cava. The postoperative course was uneventful and postoperative studies revealed good graft function with excellent blood flow in the HV.     

Risk Factors for Development of New-Onset Diabetes Mellitus and Progressive Impairment of Glucose Metabolism After Living-Donor Liver Transplantation

Background

New-onset diabetes mellitus (NODM) has a negative impact on graft and patient survivals. Hepatitis C virus (HCV) infection, high body mass index, increased donor and recipient ages, and calcineurin inhibitor (CNI) type have been identified as risk factors for the development of NODM. We aimed to elucidate the risk factors for the development of NODM and those for progressive glucose intolerance in adult living-donor liver transplant (LDLT) recipients.

Methods

We collected data from 188 primary liver transplant recipients (age > 16 years) who underwent LDLT from June 1991 to December 2011 at Hiroshima University Hospital. Risk factors for NODM and progressive impairment of glucose metabolism in pre-transplantation diabetes mellitus (DM) recipients were examined.

Results

Pre-transplantation DM was diagnosed in 32 recipients (19.3%). The overall incidence of NODM was 6.0% (8/134 recipients). Multivariate analysis revealed that old recipient age (≥55 years) is a unique predictive risk factor for developing NODM. The incident of pre-transplantation DM was significantly higher in recipients with HCV infection than in those without HCV. A high pre-transplantation triglyceride level was an independent risk factor for progressive impairment of glucose tolerance among 32 LDLT recipients with pre-transplantation DM. All of the NODM patients were being treated with tacrolimus at the time of diagnosis. Switching the CNI from tacrolimus to cyclosporine allowed one-half of the patients (4/8) to withdraw from insulin-dependent therapy. NODM and post-transplantation glucose intolerance had no negative impact on patient and graft outcomes.

Conclusions

Older age of the recipient (≥55 years) was a significant risk factor for NODM. Hypertriglyceridemia in the recipients with DM is an independent risk factor for post-transplantation progressive impairment of glucose metabolism. NODM had no negative impact on outcomes in the LDLT recipients.     

In vitro inhibitory effect of piperlonguminine isolated from Piper longum on human cytochrome P450 1A2

Piperlonguminine (PL), a major alkaloid isolated from Piper longum fruits, shows several biological activities including anti-tumor, anti-hyperlipidemic and anti-inflammatory effects. Although there have been studies of the biological effects of PL, the potential drug-interaction effect of PL following evaluation of inhibitory effects of cytochrome P450 (CYP) activities was not investigated. Here, to investigate the inhibitory effects of PL on the activities of CYP isoforms, CYP inhibition assays were conducted using a cocktail of probe substrates in pooled human liver microsome (HLMs) and human recombinant cDNA-expressed CYP. PL strongly inhibited CYP1A2-mediated phenacetin O-deethylation with an IC₅₀ value of 8.8 μM, as NADPH-independent inhibition, while other CYPs were not significantly inhibited. A Lineweaver–Burk plot resulted in the inhibition mechanism of PL being divided into two different modes, reversible competitive inhibition in a low concentration range of 0–16 μM with a K_i value of 1.39 μM and uncompetitive inhibitory behavior at a high concentration range of 16–40 μM. In addition, PL only decreased CYP 1A2-catalyzed phenacetin O-deethylase activity with IC₅₀ values of 10.0 μM in human recombinant cDNA-expressed 1A2, not 1A1. Overall, this is the first investigation of potential herb–drug interactions associated with PL conducted by identifying the competitive inhibitory effects of PL on CYP1A2 in HLMs.     

Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence

Despite their high degree of genomic similarity, reminiscent of their relatively recent separation from each other ( approximately 6 million years ago), the molecular basis of traits unique to humans vs. their closest relative, the chimpanzee, is largely unknown. This report describes a large-scale single-contig comparison between human and chimpanzee genomes via the sequence analysis of almost one-half of the immunologically critical MHC. This 1,750,601-bp stretch of DNA, which encompasses the entire class I along with the telomeric part of the MHC class III regions, corresponds to an orthologous 1,870,955 bp of the human HLA region. Sequence analysis confirms the existence of a high degree of sequence similarity between the two species. However, and importantly, this 98.6% sequence identity drops to only 86.7% taking into account the multiple insertions/deletions (indels) dispersed throughout the region. This is functionally exemplified by a large deletion of 95 kb between the virtual locations of human MICA and MICB genes, which results in a single hybrid chimpanzee MIC gene, in a segment of the MHC genetically linked to species-specific handling of several viral infections (HIV/SIV, hepatitis B and C) as well as susceptibility to various autoimmune diseases. Finally, if generalized, these data suggest that evolution may have used the mechanistically more drastic indels instead of the more subtle single-nucleotide substitutions for shaping the recently emerged primate species.     

Clinical evaluation of 61 patients with pulmonary aspergilloma

OBJECTIVE AND METHODS: We retrospectively evaluated 61 cases with pulmonary aspergilloma representing patients admitted to Nagasaki University Hospital between January 1991 to June 1998. RESULTS: Fifty-two (85%) were males and 9 (15%) were females, aged between 14 to 80 years (average, 65 years). Forty-four (72%) patients had history of old pulmonary tuberculosis. Chest radiographs showed "fungus ball" in the cavities in 42 (67%) cases while 16 (26%) cases showed thickening of the cavity wall. Aspergillus fumigatus was isolated in 24 (39%) patients. Aspergillus antigen or antibody was positive in 8 (13%) and 43 (70%) patients, respectively. Oral itraconazole was used in 16 (26%) of patients, and surgical excision was performed in 15 (25%) patients. During hospitalization or after discharge, 19 (31 %) patients died. SUMMARY AND CONCLUSION: Pulmonary aspergilloma usually occurs in elderly patients with old tuberculosis and respiratory failure. Many cases did not respond to antifungal therapy with itraconazole or amphotericin B. Our analysis indicates that more effective and appropriate therapeutic regimens are needed for the treatment of patients with pulmonary aspergilloma.     

Successful esophageal bypass operation for esophagobronchial fistula following chemotherapy for malignant lymphoma: a case report

A 72-year-old man with non-Hodgkin’s lymphoma at the tracheal bifurcation node received combination chemotherapy and subsequently developed a fistula in spite of remission of the lymphoma. Conservative therapy did not heal the fistula formation, and we chose bypass surgery using a gastric tube without thoracotomy. Ten months postoperatively, there is no evidence of lymphoma relapse and the patient lives a normal life. We consider this procedure as an available treatment for esophagobronchial fistula in case of failure to cure fistula communication by conservative therapy.