A diet high in glucose and deficient in dietary fibre causes fat accumulation in the liver without weight gain.

This study investigated whether a standard calorie diet that is high in glucose and deficient in dietary fibre (described as HGD [high glucose diet]) induces hepatic fat accumulation in mice. We evaluated hepatic steatosis at 7 days and 14 days after the commencement of the HGD. Hepatic triglycerides and areas of oil droplets increased in the HGD group both at day 7 and day 14, whereas weight gain, weight of epididymal fat, and plasma levels of triglycerides were unaffected by HGD consumption.

Prostatic Pharmacokinetic and Pharmacodynamic Analysis of Ceftazidime: Dosing Strategy for Bacterial Prostatitis.

This study aimed to develop a prostatic pharmacokinetic model of ceftazidime and suggest more effective dosing strategy for the bacterial prostatitis, based on a site-specific pharmacokinetic and pharmacodynamic perspective. Subjects were prostatic hyperplasia patients prophylactically receiving a 0.5-h infusion of 1.

Pulmonary Pharmacokinetic and Pharmacodynamic Evaluation of Ampicillin/Sulbactam Regimens for Pneumonia Caused by Various Bacteria, including .

This study aimed to assess the dosing regimens of ampicillin/sulbactam for pneumonia based on pulmonary pharmacokinetic (PK)/pharmacodynamic (PD) target attainment. Using the literature data, we developed pulmonary PK models and estimated the probabilities of attaining PK/PD targets in lung tissue. Against bacteria other than (the general treatment), the PK/PD target was set as both 50% time above the minimum inhibitory concentration (T > MIC) for ampicillin and 50% T > 0.

Pharmacodynamic Evaluation of Ampicillin-sulbactam in Pediatric Patients Using Plasma and Urine Data.

Background: We aimed to develop population pharmacokinetic (PK) models of ampicillin and sulbactam using pooled data analysis and to optimize dosing regimens of ampicillin-sulbactam (combination ratio of 2:1) in pediatric patients.

Methods: Population PK models of ampicillin and sulbactam were separately developed by simultaneously fitting plasma and urine data from pediatric patients in 14 published studies. Based on these models, we estimated the probability of attaining a pharmacodynamic (PD) target [50% of time that free drug concentrations above the minimum inhibitory concentration, 50% fT > minimum inhibitory concentration (MIC)] against MIC90 [MIC that blocked the growth of 90% of the strains] of common bacteria in community-acquired pneumonia.

[Assessment of Renal Function and Simulation Using Serum Cystatin-C in an Elderly Patient with Uncontrollable Plasma Vancomycin Levels Due to Muscular Dystrophy: A Case Report].

Herein, we describe a case of an elderly patient with muscular dystrophy for whom control of the plasma vancomycin (VCM) concentration proved difficult when he developed a catheter-related bloodstream infection. The pharmacist initially carried out therapeutic drug monitoring using an estimate of the creatinine clearance (CL) level, which was based on the serum creatinine (SCr) and serum cystatin-C (CysC) levels, but was ultimately unable to control the plasma VCM concentration. Therefore, the plasma VCM concentration was predicted ex post facto using population pharmacokinetic parameters as a covariate; that is, directly including the glomerular filtration rate (GFR) estimated from the CysC level, which is not affected by the muscle mass.

Prostatic Pharmacokinetic/Pharmacodynamic Evaluation of Ampicillin-Sulbactam for Bacterial Prostatitis and Preoperative Prophylaxis.

This study aims to define the penetration of ampicillin and sulbactam into prostate tissue, develop a prostatic pharmacokinetic model of each drug, and assess the appropriateness of ampicillin-sulbactam regimens for the treatment of prostatitis and the prophylaxis of postoperative infection, based on a pharmacokinetic and pharmacodynamic simulation. Subjects were prostatic hyperplasia patients prophylactically receiving a 0.5-hour infusion of 1.

Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Simulation of Piperacillin/Tazobactam for Dosing Optimization in Late Elderly Patients with Pneumonia.

The aim of this study was to develop a population pharmacokinetic model for piperacillin (PIPC)/tazobactam (TAZ) in late elderly patients with pneumonia and to optimize the administration planning by applying pharmacokinetic/pharmacodynamic (PK/PD) criteria. PIPC/TAZ (total dose of 2.25 or 4.

Inpatient Expenditures Attributable to Hospital-Onset Clostridium difficile Infection: A Nationwide Case-Control Study in Japan.

Background: Hospital-onset Clostridium difficile infections (CDIs) have a considerable clinical and economic impact on patients and payers. Quantifying the economic impact of CDIs can guide treatment strategies. However, previous studies have generally focused on acute care hospitals, and few have included cost estimates from non-acute care hospitals such as long-term care facilities.

Development of molecular diagnostic protocols for detecting three types of Entamoeba from diarrheal and asymptomatic pigs and environmental moist soils.

Entamoeba suis and Entamoeba polecki subtypes (ST) 1 and 3 have recently been implicated in disease outbreaks in pigs. However, the distributions of these parasites in Japan and the potential sources of infection on farms still remain unclear. Here, we examined a farm of fattening/growing pigs with abnormal feces in Kagoshima Prefecture, Japan, and found the presence of parasites in the farm environment.

Vancomycin induces reactive oxygen species-dependent apoptosis via mitochondrial cardiolipin peroxidation in renal tubular epithelial cells.

Vancomycin (VCM) is a first-line antibiotic for serious infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is one of the most complaint in VCM therapy. We previously reported that VCM induced apoptosis in a porcine proximal tubular epithelial cell line (LLC-PK1), in which mitochondrial complex I may generate superoxide, leading to cell death.

Evaluation of Teicoplanin Trough Values After the Recommended Loading Dose in Children With Associated Safety Analysis.

Background: This study evaluated whether the recommended teicoplanin loading dose (3 loading doses of 10 mg/kg every 12 hours) achieves a 15-30 μg/mL trough levels in 26 children (2-16 years). In addition, we examined the incidences of renal impairment and hepatic dysfunction in children treated with teicoplanin.

Methods: This retrospective study was conducted between October 2008 and March 2014.

Thiazolobenzyne: a versatile intermediate for multisubstituted benzothiazoles.

Thiazolobenzyne, which is a benzyne species fused with a thiazole ring, was efficiently generated via an iodine-magnesium exchange reaction of an ortho-iodoaryl triflate-type precursor using a trimethylsilylmethyl Grignard reagent as an activator. A wide range of arynophiles reacted efficiently with the thiazolobenzynes generated by this method to afford various multisubstituted benzothiazoles.

Direct thioamination of arynes via reaction with sulfilimines and migratory N-arylation.

A novel method for preparing a diverse range of o-sulfanylanilines is described. Direct thioamination of arynes with sulfilimines gives o-sulfanylanilines, involving C-N and C-S bond formations and migratory N-arylation.

A mild and facile synthesis of aryl and alkenyl sulfides via copper-catalyzed deborylthiolation of organoborons with thiosulfonates.

An efficient deborylthiolation of aryl- and alkenylborons with thiosulfonates has been achieved under mild conditions using a copper catalyst. All steps of the experimental process were free from unpleasant odors. The mild reaction conditions as well as ready availability of boron compounds and thiosulfonates enabled easy access to an array of sulfides, including those bearing sensitive functional groups.

An Alternative Method for Generating Arynes from ortho-Silylaryl Triflates: Activation by Cesium Carbonate in the Presence of a Crown Ether.

An alternative method for generating arynes from ortho-silylaryl triflates using cesium carbonate and 18-crown-6 is reported. The method was efficiently applied to a variety of reactions between several arynes and arynophiles. We also demonstrated that the efficiency of aryne generation is significantly affected by the alkali metal countercation of the carbonate.

Evaluation of teicoplanin concentrations and safety analysis in neonates.

The aims of this study were (i) to evaluate the relationship between teicoplanin (TEIC) dosage and subsequent trough concentration, (ii) to investigate factors that affect TEIC serum concentration fluctuations and (iii) to examine the association between serum concentration of TEIC and adverse reactions in neonates. A total of 37 eligible neonates (<28 days of age) treated with TEIC from 2008-2012 were included in this study. The median trough concentration in the loading dose regimen of >12-16 mg/kg on Day 1, followed by >6-8 mg/kg every 24 h (q24 h) was 19.

Unified approach to catechin hetero-oligomers: first total synthesis of trimer EZ-EG-CA isolated from Ziziphus jujuba.

A catechin hetero-trimer isolated from Ziziphus jujuba has been synthesized. Among three constituent monomers, (-)-epiafzelechin and (-)-epigallocatechin were prepared by de novo synthesis. Trimer formation relied on the unified approach to oligomers based on the bromo-capping and the orthogonal activation, reaching the reported structure of the natural product.

Simplified dosing regimens of teicoplanin for patient groups stratified by renal function and weight using Monte Carlo simulation.

The purpose of this study was (i) to determine the optimal dosage of teicoplanin for each patient group stratified by renal function and weight based on a population pharmacokinetic model and observed distribution of patient characteristics and (ii) to develop new simplified dosing regimens designed to achieve 15-30 μg/mL. Patient data were collected retrospectively from routine therapeutic drug monitoring files of adult patients who were given the standard loading dose regimen of teicoplanin (400 mg twice on Day 1, followed by 400 mg once daily for 2 days) and whose trough concentration was measured just before administration on Day 4. Monte Carlo simulation was conducted to estimate the trough concentration at 72 h after the initial loading dose (C(min)(72 h)) and at steady state (C(ss)(min)).

Mitochondrial superoxide production contributes to vancomycin-induced renal tubular cell apoptosis.

Vancomycin chloride (VCM), a glycopeptide antibiotic, is widely used for the therapy of infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is a major adverse effect in VCM therapy. In this study, we investigated the cellular mechanisms underlying VCM-induced renal tubular cell injury in cultured LLC-PK1 cells.

Activation of p38 MAPK by oxidative stress underlying epirubicin-induced vascular endothelial cell injury.

Epirubicin, an anthracycline antitumor drug, often causes vascular injury such as vascular pain, phlebitis, and necrotizing vasculitis. However, an effective prevention for the epirubicin-induced vascular injury has not been established. The purpose of this study is to identify the mechanisms of cell injury induced by epirubicin in porcine aorta endothelial cells (PAECs).

L type Ca²+ channel blockers prevent oxaliplatin-induced cold hyperalgesia and TRPM8 overexpression in rats.

Background: Oxaliplatin is an important drug used in the treatment of colorectal cancer. However, it frequently causes severe acute and chronic peripheral neuropathies. We recently reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats, and that oxalate derived from oxaliplatin is involved in the cold hyperalgesia.