Comparison of Ertapenem and Ceftriaxone Therapy for Acute Pyelonephritis and Other Complicated Urinary Tract Infections in Korean Adults: A Randomized, Double-Blind, Multicenter Trial

The efficacy and safety of ertapenem, 1 g once daily, were compared with that of ceftriaxone, 2 g once daily, for the treatment of adults with acute pyelonephritis (APN) and complicated urinary tract infections (cUTIs) in a prospective, multicenter, double-blinded, randomized study. After ≥ 3 days of parenteral study therapy, patients could be switched to an oral agent. Of 271 patients who were initially stratified by APN (n = 210) or other cUTIs (n = 61), 66 (48.9%) in the ertapenem group and 71 (52.2%) in the ceftriaxone group were microbiologically evaluable. The mean duration of parenteral and total therapy, respectively, was 5.6 and 13.8 days for ertapenem and 5.8 and 13.8 days for ceftriaxone. The most common pathogen was Escherichia coli. At the primary efficacy endpoint 5-9 days after treatment, 58 (87.9%) patients in the ertapenem group and 63 (88.7%) in the ceftriaxone had a favorable microbiological response. When compared by stratum and severity, the outcomes in the two groups were equivalent. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. The results indicate that ertapenem is highly effective and safe for the treatment of APN and cUTIs

Emodin Regulates Glucose Utilization by Activating AMP-activated Protein Kinase

AMP-activated protein kinase has been described as a key signaling protein that can regulate energy homeostasis. Here, we aimed to characterize novel AMP-activated kinase (AMPK)-activating compounds that have a much lower effective concentration than metformin. As a result, emodin, a natural anthraquinone derivative, was shown to stimulate AMPK activity in skeletal muscle and liver cells. Emodin enhanced GLUT4 translocation and [C-14]glucose uptake into the myotube in an AMPK-dependent manner. Also, emodin inhibited glucose production by suppressing the expression of key gluconeogenic genes, such as phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, in hepatocytes. Furthermore, we found that emodin can activate AMPK by inhibiting mitochondrial respiratory complex I activity, leading to increased reactive oxygen species and Ca2+/calmodulin-dependent protein kinase kinase activity. Finally, we confirmed that a single dose administration of emodin significantly decreased the fasting plasma glucose levels and improved glucose tolerance in C57Bl/6J mice. Increased insulin sensitivity was also confirmed after daily injection of emodin for 8 days using an insulin tolerance test and insulin-stimulated PI3K phosphorylation in wild type and high fat diet-induced diabetic mouse models. Our study suggests that emodin regulates glucose homeostasis in vivo by AMPK activation and that this may represent a novel therapeutic principle in the treatment of type 2 diabetic models.close

The androgenic anabolic steroid tetrahydrogestrinone produces dioxin-like effects via the aryl hydrocarbon receptor

For a long time, athletes have used androgenic anabolic steroids (AASs) in an inappropriate and veiled manner with the aim of improving exercise performance or for cosmetic purposes. Abuse of AASs triggers adverse effects such as hepatocarcinogenesis, heart attacks, and aggressive behavior. However, AAS-induced toxicity is not completely understood at the molecular level. In the present study, we showed, by performing a dioxin response element (DRE)-luciferase reporter gene assay, that tetrahydrogestrinone (THG), a popular and potent androgen receptor agonist, has dioxin-like effects. In addition, we showed that THG increased cytochrome P-450 1A1 (CYP1A1) mRNA and protein levels, and enzyme activity. The gene encoding CYP1A1 is involved in phase 1 xenobiotic metabolism and a target gene of the aryl hydrocarbon receptor (AhR). Using the AhR antagonist CH-223191, we also examined whether the effects of THG on DRE activation depended on AhR. Our results suggest that synthetic anabolic steroids may have dioxin-like side effects that can disturb endocrine systems and may cause other side effects including cancer through AhR.close2

Muscle fiber type-dependence effect of exercise on genomic networks in aged mice models

Skeletal muscles are made up of various muscle fiber type including slow and fast-twitch fibers. Because each muscle fiber has its own physiological characteristics, the effects of aging and exercise vary depending on the type of muscle fiber. We used bioinformatics screening techniques such as differentially expressed gene analysis, gene ontology analysis and gene set enrichment analysis, to try to understand the genetic differences between muscle fiber types. The experiment and gene expression profiling in this study used the soleus (SOL, slow-twitch muscle) and gastrocnemius (GAS, fast-twitch muscle). According to our findings, fatty acid metabolism is significantly up-regulated in SOL compared to GAS, whereas the glucose metabolism pathway is significantly down-regulated in SOL compared to GAS. Furthermore, apoptosis and myogenesis patterns differ between SOL and GAS. SOL did not show differences in apoptosis due to the aging effect, but apoptosis in GAS was significantly up-regulated with age. Apoptosis in GAS of old groups is significantly reduced after 4 weeks of aerobic exercise, but no such finding was found in SOL. In terms of myogenesis, exercise intervention up-regulated this process in GAS of old groups but not in SOL. Taken together, muscle fiber type significantly interacts with aging and exercise. Despite the importance of the interaction between these factors, large-scale gene expression data has rarely been studied. We hope to contribute to a better understanding of the relationship between muscle fiber type, aging and exercise at the molecular level.N

Apolipoprotein a1 increases mitochondrial biogenesis through AMP-activated protein kinase

Apolipoprotein a1, which is a major lipoprotein component of high-density lipoprotein (HDL), was reported to decrease plasma glucose in type 2 diabetes. Although recent studies also have shown that apolipoprotein a1 is involved in triglyceride (TG) metabolism, the mechanisms by which apolipoprotein a1 modulates TG levels remain largely unexplored. Here we demonstrated that apolipoprotein a1 increased mitochondrial DNA and mitochondria contents through sustained AMPK activation in myotubes. This resulted in enhanced fatty acid oxidation and attenuation of free fatty acid-induced insulin resistance features in skeletal muscle. The increment of mitochondria was mediated through induction of transcription factors, such as peroxisome proliferatoractivated receptor gamma coactivator 1-alpha (PGC-1 alpha) and nuclear transcription factor 1 (NRF-1). The inhibition of AMPK by a pharmacological agent inhibited the induction of mitochondrial biogenesis. Increase of AMPK phosphorylation by apolipoprotein a1 occurs through activation of upstream kinase LKB1. Finally, we confirmed that scavenger receptor Class B, type 1 (SR-B1) is an important receptor for apolipoprotein a1 in stimulating AMPK pathway and mitochondrial biogenesis. Our study suggests that apolipoprotein a1 can alleviate obesity related metabolic disease by inducing AMPK dependent mitochondrial biogenesis. (C) 2015 Elsevier Inc. All rights reservedclose0

Involvement of exercise-induced macrophage migration inhibitory factor in the prevention of fatty liver disease

Physical inactivity can lead to obesity and fat accumulation in various tissues. Critical complications of obesity include type II diabetes and nonalcoholic fatty liver disease (NAFLD). Exercise has been reported to have ameliorating effects on obesity and NAFLD. However, the underlying mechanism is not fully understood. We showed that liver expression of macrophage migration inhibitory factor (MIF) was increased after 4 weeks of treadmill exercise. Phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase in human hepatocyte cell lines was enhanced after MIF treatment. These responses were accompanied by increases in lipid oxidation. Moreover, inhibition of eitherAMPKor cluster of differentiation 74 resulted in inhibition of MIF-induced lipid oxidation. Furthermore, the administration of MIF to a human hepatocyte cell line and mice liver reduced liver X receptor agonist-induced lipid accumulation. Taken together, these results indicate that MIF is highly expressed in the liver during physical exercise and may prevent hepatic steatosis by activating the AMPK pathway.close0