Antifungal cyclic depsipeptide, eujavanicin A, isolated from Eupenicillium javanicum

In the course of searching for new antifungal agents, a new cyclic depsipeptide, eujavanicin A (1), was isolated from Eupenicillium javanicum as an antifungal agent against the human pathogenic filamentous fungus Aspergillus fumigatus. The structure of 1 was established by spectroscopic and chemical investigations. The absolute stereochemistry was elucidated by Marfey's method and by chiral HPLC analysis.     

Stages of a Transtheoretical Model as Predictors of the Decline in Estimated Glomerular Filtration Rate: A Retrospective Cohort Study

BackgroundThe transtheoretical model (TTM) is composed of the multiple stages according to patient’s consciousness and is believed to lead people to realize the importance of healthier behaviors. We examined the association of TTM stages with the decline of estimated glomerular filtration rate (eGFR).MethodsWe used the annual health checkup data and health insurance claims data of the Japan Health Insurance Association in Kyoto Prefecture between April 2012 and March 2016. TTM stages of change obtained from questionnaires at the first health checkup and categorized into six groups. The primary outcome was defined as a more than 30% decline in eGFR from the first health checkup. We fitted multivariable Cox proportional-hazards model for time-to-event analyses adjusting for age, sex, eGFR, body mass index, blood pressure, blood sugar, dyslipidemia, uric acid, urinary protein, and existence of kidney diseases at first health checkup.ResultsWe analyzed 239,755 employees and the mean follow-up was 2.9 (standard deviation, 1.2) years. As compared with the stage 1 group, the risk of eGFR decline was significantly low in the stage 3 group (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.65–0.91); stage 4 group (HR 0.80; 95% CI, 0.65–0.98); and stage 5 group (HR 0.79; 95% CI, 0.66–0.95).ConclusionCompared with the precontemplation stage (stage 1), the preparation, action and maintenance stages (stages 3, 4, and 5), were associated with a lower risk of eGFR decline.Key words: transtheoretical model, chronic kidney disease, kidney injury, stage of change, more than 30% decline in estimated glomerular filtration rate     

Hepatitis B Virus Infection Predicts Extrahepatic Metastasis After Hepatic Resection in Patients With Large Hepatocellular Carcinoma

Background Although extrahepatic metastasis occurs rarely after hepatic resection for hepatocellular carcinoma (HCC), the prognosis of these patients is extremely poor. Predictors of extrahepatic metastasis have not been fully investigated. Methods To identify predictors of extrahepatic metastasis after resection, we retrospectively investigated 77 patients with HCC tumors >50 mm in diameter who underwent hepatic resection. We investigated correlations between postoperative extrahepatic metastasis and clinicopathologic factors as well as extrahepatic metastasis-free survival rate by log rank test and predictors of extrahepatic metastasis by univariate and multivariate logistic regression models. Results Hepatitis B surface antigen (HBs-Ag) was found in 25 (32.5%) of 77 patients, and extrahepatic metastasis occurred in 26 (33.8%). Patients with extrahepatic metastasis showed better liver function and a high occurrence of HBs-Ag positivity than those without. The 5-year extrahepatic metastasis-free survival rate was worse in patients with HBs-Ag positivity, larger tumors (≥70 mm), higher alfa-fetoprotein level (≥300 ng/mL), and lower indocyanine green retention rate at 15 minutes (ICGR₁₅) (<15%) than in those without. By univariate logistic regression analysis, HBs-Ag positivity, larger HCC tumor (≥70 mm), lower ICGR₁₅ (<15%), and lower preoperative lymphocyte count (<1000/mm³) were predictors of extrahepatic metastasis (P < .1). By multivariate analysis, HBs-Ag positivity was an independent predictor of postoperative extrahepatic metastasis (P = .04). Conclusions In patients positive for HBs-Ag, radiologic examination of extrahepatic organs should be performed as a part of the postoperative surveillance. Hepatitis B virus infection may promote establishment of extrahepatic metastasis.     

New methods of control against postoperative methicillin-resistantStaphylococcus aureus infection

The incidence of postoperative infections caused by methicillin-resistantStaphylococcus aureus (MRSA) in Japan has been increasing dramatically. In March 1990, we assigned special doctors in infection control (infection control doctor, ICD), and defined comprehensive controls against MRSA infection. A total of 3 536 cases of digestive tract surgery performed at our department were studied during the period between September 1987 and August 1997. We changed the use of antibiotics to prevent postoperative infection. Cefazolin (CEZ) was employed for surgery of the upper digestive tract, including esophagus, stomach, duodenum, and gallbladder. Cefotiam (CTM) was employed for surgery of the lower digestive tract, liver, and pancreas. In esophageal resection, the tracheal tube was extracted during the early postoperative period, and for cervical esophagogastroanastomosis, the autosuture was changed to layer-to-layer anastomosis. We have achieved successful control of postoperative MRSA infection, the incidence having decreased to 0.3% (9/2703). In conclusion, our methods of control against postoperative MRSA infection implies that comprehensive measures of prevention, including the reviewed specification and usage of antibiotics and operation management, have been well implemented. This value is the lowest and the first of any domestic hospital or institute in Japan, suggesting a continued and significant decrease.     

Oxidative stress induced by iron released from transferrin in low pH peritoneal dialysis solution

Background. Transferrin binds extracellular iron and protectstissues from iron-induced oxidative stress. The binding of ironand transferrin is pH dependent and conventional peritonealdialysis (PD) solutions have unphysiologically low pH values.Herein, we investigated whether conventional PD solution releasesiron from transferrin and if the released iron causes oxidativestress. Methods. Effects of PD solutions on iron binding to transferrinwere examined with purified human transferrin and transferrinin dialysates drained from PD patients. Oxidative stress inducedby iron released from transferrin was evaluated in terms ofthe formation of thiobarbituric acid reactive substance (TBARS)and protein carbonylation in the human red blood cell (RBC)membrane. The iron deposition in peritoneal tissue from PD patientswas evaluated by Perls' staining with diaminobenzidine intensification. Results. Low pH PD solution released iron from transferrin.This iron release occurred within 1 min. Iron release was notobserved in neutralized PD solution. Iron released from transferrinin low pH PD solution increased TBARS formation and proteincarbonylation in the human RBC membrane. Iron deposition, whichis prominent in the fibrotic area facing the peritoneal cavity,was observed in the peritoneum of PD patients. Conclusions. Iron released from transferrin in low pH PD solutioncan produce oxidative stress in the peritoneum of a PD patient.Neutralizing PD solution can avoid this problem. Iron depositionin the peritoneum may participate in the pathogenesis of peritonealfibrosis in PD patients.     

Comparison of Near-Infrared Spectroscopy and Laser Doppler Flowmetry for Detecting Decreased Hepatic Inflow in the Porcine Liver

Hepatic artery and portal vein thrombosis are devastating complications of partial liver transplantation. Early detection of inflow complications is important, as re-reconstruction can salvage the graft. Near-infrared spectroscopy or laser Doppler flowmetry can be used to detect tissue oxygenation or microcirculation on the liver surface. The aim of this study was to examine which of these two methods better detects changes in hepatic inflow. Sangen-strain pigs (n = 5) were used. The tips of the near-infrared spectroscopy and laser Doppler flowmetry probes were placed separately on the surface of the right liver. Inflow to the liver was controlled during the following seven conditions: control (not clamped), half- and totally clamped portal vein, half- and totally clamped hepatic artery, and half- and totally clamped portal vein and artery. Tissue blood flow was calculated using laser Doppler flowmetry. Oxyhemoglobin, deoxyhemoglobin, and the tissue oxygenation index were measured and calculated using a near-infrared spectroscopy system. The tissue blood flow and oxygenation index could not be used to differentiate between the half-clamped portal vein, half-clamped hepatic artery, and totally clamped portal vein conditions. The oxyhemoglobin minus deoxyhemoglobin value was significantly decreased after half or total clamping of the portal vein or hepatic artery (p <. 001 for each condition). The findings of the present study indicate that near-infrared spectroscopy was more sensitive than Doppler flowmetry for detecting changes in hepatic tissue inflow from the liver surface.     

Clinical impact of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer’s disease: a multicenter study

Annals of Nuclear Medicine - Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of...