Early Therapeutic Drug Monitoring Optimizes Teicoplanin Use in Febrile Neutropenic Patients with Hematological Malignancies.

Introduction: A target trough concentration (C) of teicoplanin ≥ 15-20 mg/L between the fourth and sixth day has been suggested for severe infections or management of febrile neutropenia (FN). Owing to no reports discussing the impact of early target attainment on treatment outcomes, this study aimed to evaluate the dose-C relationship and clinical outcome and estimate the optimal early target C for FN in patients with hematological malignancies.

Methods: This single-center, prospective study enrolled patients with hematological malignancies who were treated with teicoplanin either as an empirical antibiotic for FN or as targeted treatment for Gram-positive bacteria.

Maternal Plasma Lipids During Pregnancy, Insulin-like Growth Factor-1, and Excess Fetal Growth.

Context: Maternal lipids during pregnancy and placental growth factors are associated with excess fetal growth. However, how these factors interact to increase the risk of delivering large-for-gestational-age (LGA) neonates remains unclear. In this study, we investigated the relationship between maternal plasma triglycerides (TGs) and free fatty acids (FFAs) during pregnancy, cord blood insulin-like growth factors (IGF), and LGA.

Delayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke.

Induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) are a promising source of tailor-made cell therapy for neurological diseases. However, major obstacles to clinical use still exist. To circumvent complications related to intracerebral administration, we implanted human iPSC-NPCs epidurally over the peri-infarct cortex 7 days after permanent middle cerebral artery occlusion in adult rats.

A polyphenol-rich fraction obtained from table grapes decreases adiposity, insulin resistance and markers of inflammation and impacts gut microbiota in high-fat-fed mice.

The objective of this study was to determine if consuming an extractable or nonextractable fraction of table grapes reduced the metabolic consequences of consuming a high-fat, American-type diet. Male C57BL/6J mice were fed a low fat (LF) diet, a high fat (HF) diet, or an HF diet containing whole table grape powder (5% w/w), an extractable, polyphenol-rich (HF-EP) fraction, a nonextractable, polyphenol-poor (HF-NEP) fraction or equal combinations of both fractions (HF-EP+NEP) from grape powder for 16weeks. Mice fed the HF-EP and HF-EP+NEP diets had lower percentages of body fat and amounts of white adipose tissue (WAT) and improved glucose tolerance compared to the HF-fed controls.

Table grape consumption reduces adiposity and markers of hepatic lipogenesis and alters gut microbiota in butter fat-fed mice.

Our objective was to determine if consuming table grapes reduces adiposity and its metabolic consequences and alters gut microbiota in mice fed a high-fat (HF), butter-rich diet. C57BL/6J mice were fed a low-fat (LF) diet or HF diet with 3% or 5% grapes for 11weeks. Total body and inguinal fat were moderately but significantly reduced in mice fed both levels of grapes compared to their controls.

Alterations of a Cellular Cholesterol Metabolism Network Are a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease.

Obesity is linked to type 2 diabetes (T2D) and cardiovascular diseases; however, the underlying molecular mechanisms remain unclear. We aimed to identify obesity-associated molecular features that may contribute to obesity-related diseases. Using circulating monocytes from 1,264 Multi-Ethnic Study of Atherosclerosis (MESA) participants, we quantified the transcriptome and epigenome.

Low level of trans-10, cis-12 conjugated linoleic acid decreases adiposity and increases browning independent of inflammatory signaling in overweight Sv129 mice.

The objective of this study was to determine the extent to which a low level of trans-10, cis-12 (10,12) conjugated linoleic acid (CLA) decreases adiposity and increases browning in overweight mice, its dependence on inflammatory signaling and potential synergistic effects of daily exercise. Young, Sv129 male mice were fed a high-fat diet for 5 weeks to make them fat and glucose intolerant and then switch them to a low-fat diet with or without 0.1% 10,12 CLA, sodium salicylate or exercise for another 7 weeks.

Uncleaved ApoM signal peptide is required for formation of large ApoM/sphingosine 1-phosphate (S1P)-enriched HDL particles.

Apolipoprotein M (apoM), a plasma sphingosine 1-phosphate (S1P) carrier, associates with plasma HDL via its uncleaved signal peptide. Hepatocyte-specific apoM overexpression in mice stimulates formation of both larger nascent HDL in hepatocytes and larger mature apoM/S1P-enriched HDL particles in plasma by enhancing hepatic S1P synthesis and secretion. Mutagenesis of apoM glutamine 22 to alanine (apoM(Q22A)) introduces a functional signal peptidase cleavage site.

An abundant dysfunctional apolipoprotein A1 in human atheroma.

Recent studies have indicated that high-density lipoproteins (HDLs) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma are dysfunctional and are extensively oxidized by myeloperoxidase (MPO). In vitro oxidation of either apoA1 or HDL particles by MPO impairs their cholesterol acceptor function. Here, using phage display affinity maturation, we developed a high-affinity monoclonal antibody that specifically recognizes both apoA1 and HDL that have been modified by the MPO-H2O2-Cl(-) system.

Myeloid cell-specific ABCA1 deletion does not worsen insulin resistance in HF diet-induced or genetically obese mouse models.

Obesity-associated low-grade chronic inflammation plays an important role in the development of insulin resistance. The membrane lipid transporter ATP-binding cassette transporter A1 (ABCA1) promotes formation of nascent HDL particles. ABCA1 also dampens macrophage inflammation by reducing cellular membrane cholesterol and lipid raft content.

The phospholipase C inhibitor U73122 attenuates trans-10, cis-12 conjugated linoleic acid-mediated inflammatory signaling and insulin resistance in human adipocytes.

We have demonstrated that trans-10, cis-12 conjugated linoleic acid (18:2t10,c12)-mediated delipidation of human adipocytes was dependent on increased intracellular calcium and activation of inflammatory signaling in human primary adipocytes. These data are consistent with the actions of diacylglycerol and inositol triphosphate derived from phospholipase C (PLC)-dependent cell signaling. To test the hypothesis that PLC was an upstream activator of these cellular responses to 18:2t10,c12, primary cultures of human adipocytes were pretreated with 1-[6-((17β-3-methoxyestra-1,3,5 (10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione (U73122), a universal PLC inhibitor, followed by 18:2t10,c12 treatment.

Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice.

The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat. Young male mice were fed three combinations of fatty acids at three doses (0.06%, 0.

Diacylglycerol kinase inhibitor R59022 attenuates conjugated linoleic acid-mediated inflammation in human adipocytes.

Diacylglycerol kinases (DGK) convert diacylglycerol to phosphatidic acid, which has been reported to stimulate calcium release from the endoplasmic reticulum. Based on our published data showing that trans-10, cis-12 conjugated linoleic acid (t10,c12 CLA)-mediated intracellular calcium accumulation is linked to inflammation and insulin resistance, we hypothesized that inhibiting DGKs with R59022 would prevent t10,c12 CLA-mediated inflammatory signaling and insulin resistance in human adipocytes. Consistent with our hypothesis, R59022 attenuated t10,c12 CLA-mediated i) increased gene expression and protein secretion of interleukin (IL)-8, IL-6, and monocyte chemoattractant protein-1 (MCP-1); ii) increased activation of extracellular signal-related kinase (ERK), cJun-NH2-terminal kinase (JNK), and cJun; iii) increased intracellular calcium levels; iv) suppressed mRNA or protein levels of peroxisome proliferator activated receptor γ, adiponectin, and insulin-dependent glucose transporter 4; and v) decreased fatty acid and glucose uptake and triglyceride content.

Differential effects of grape powder and its extract on glucose tolerance and chronic inflammation in high-fat-fed obese mice.

The objective of this study was to determine the anti-inflammatory properties of grape powder (GP) or GP extract (GE) and examine (1) which polyphenol metabolites in GE were bioavailable, (2) the impact of GP and GE on glucose tolerance and inflammation in obese mice, and (3) if bioavailable polyphenols in GE decrease markers of inflammation in primary adipocytes. In experiment 1, C57BL/6J mice were gavaged with GE and serum polyphenols were measured. In experiment 2, mice were fed high-fat diets supplemented with 3% GP or 0.

Potential mechanisms by which polyphenol-rich grapes prevent obesity-mediated inflammation and metabolic diseases.

Obesity and metabolic disease-related health problems (e.g., type 2 diabetes, atherosclerosis, and hypertension) are the most prevalent nutrition-related issues in the United States.

Quercetin is equally or more effective than resveratrol in attenuating tumor necrosis factor-{alpha}-mediated inflammation and insulin resistance in primary human adipocytes.

Background: Quercetin and trans-resveratrol (trans-RSV) are plant polyphenols reported to reduce inflammation or insulin resistance associated with obesity. Recently, we showed that grape powder extract, which contains quercetin and trans-RSV, attenuates markers of inflammation in human adipocytes and macrophages and insulin resistance in human adipocytes. However, we do not know how quercetin and trans-RSV individually affected these outcomes.

Grape powder extract attenuates tumor necrosis factor α-mediated inflammation and insulin resistance in primary cultures of human adipocytes.

Grapes are rich in phenolic phytochemicals that possess anti-oxidant and anti-inflammatory properties. However, the ability of grape powder extract (GPE) to prevent inflammation and insulin resistance in human adipocytes caused by tumor necrosis factor α (TNFα), a cytokine elevated in plasma and white adipose tissue (WAT) of obese, diabetic individuals, is unknown. Therefore, we examined the effects of GPE on markers of inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes treated with TNFα.

Xanthones from mangosteen inhibit inflammation in human macrophages and in human adipocytes exposed to macrophage-conditioned media.

Obesity-associated inflammation is characterized by recruitment of macrophages (MPhi) into white adipose tissue (WAT) and production of inflammatory cytokines, leading to the development of insulin resistance. The xanthones, alpha- and gamma-mangostin (MG), are major bioactive compounds found in mangosteen that are reported to have antiinflammatory and antioxidant properties. Thus, we examined the efficacy of MG to prevent lipopolysaccharide (LPS)-mediated inflammation in human MPhi (differentiated U937 cells) and cross-talk with primary cultures of newly differentiated human adipocytes.

Titanium implants alter endothelial function and vasoconstriction via a protein kinase C-regulated pathway.

The application of titanium (Ti) alloy in joint prostheses is a good choice in orthopedic reconstruction. An elevated serum concentration of Ti has been shown in the patients with loosened knee prostheses. The precise actions of elevated Ti on the circulation remain unclear.

Xanthones from mangosteen prevent lipopolysaccharide-mediated inflammation and insulin resistance in primary cultures of human adipocytes.

The xanthones, alpha- and gamma-mangostin (MG), are major bioactive compounds found in mangosteen and are reported to have antiinflammatory properties in several murine models. Given the association between obesity, chronic low-grade inflammation, and insulin resistance, we examined the effects of alpha- and gamma-MG on markers of inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes treated with lipopolysaccharide (LPS). alpha- and gamma-MG decreased the induction by LPS of inflammatory genes, including tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, monocyte chemoattractant protein-1, and Toll-like receptor-2.

Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: mechanisms of action and implications.

This review highlights the inflammatory and insulin-antagonizing effects of saturated fatty acids (SFA), which contribute to the development of metabolic syndrome. Mechanisms responsible for these unhealthy effects of SFA include: 1) accumulation of diacylglycerol and ceramide; 2) activation of nuclear factor-kappaB, protein kinase C-, and mitogen-activated protein kinases, and subsequent induction of inflammatory genes in white adipose tissue, immune cells, and myotubes; 3) decreased PPARgamma coactivator-1 alpha/beta activation and adiponectin production, which decreases the oxidation of glucose and fatty acids (FA); and 4) recruitment of immune cells like macrophages, neutrophils, and bone marrow-derived dendritic cells to WAT and muscle. Several studies have demonstrated potential health benefits of substituting SFA with unsaturated FA, particularly oleic acid and (n-3) FA.

Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol.

Inflammation plays a role in trans-10, cis-12 (10,12)-conjugated linoleic acid (CLA)-mediated delipidation and insulin resistance in adipocytes. Given the anti-inflammatory role of resveratrol (RSV), we hypothesized that RSV would attenuate inflammation and insulin resistance caused by 10,12 CLA in human adipocytes. RSV blocked 10,12 CLA induction of the inflammatory response by preventing activation of extracellular signal-related kinase and induction of inflammatory gene expression (i.

Hyperglycemia enhances adipogenic induction of lipid accumulation: involvement of extracellular signal-regulated protein kinase 1/2, phosphoinositide 3-kinase/Akt, and peroxisome proliferator-activated receptor gamma signaling.

The molecular events of hyperglycemia-triggered increase in adipogenic induction of lipid accumulation remain unclear. We examined the effects of hyperglycemia on adipogenic induction of lipid accumulation and its involved signaling molecules, such as phosphoinositide 3-kinase (PI3K), ERKs, and peroxisome proliferator-activated receptor gamma (PPAR gamma). Bone marrow-derived mesenchymal stem cells (MSCs) isolated from FVB/N mice were capable of differentiating into adipocytes in adipogenic medium.