A5067724612- Cardiac Arrest and Resuscitation
- Adipokines, Inflammation, and Metabolic Diseases
- Thermal Regulation in Medicine
- Adipose Tissue and Metabolism
- Traumatic Brain Injury and Neurovascular Disturbances
- Nitric Oxide and Endothelin Effects
- Peroxisome Proliferator-Activated Receptors
- Neonatal Respiratory Health Research
- Infant Development and Preterm Care
- Cardiovascular Function and Risk Factors
- Regulation of Appetite and Obesity
- Immune Cell Function and Interaction
- Metabolism, Diabetes, and Cancer
- Respiratory Support and Mechanisms
- Intensive Care Unit Cognitive Disorders
- Heart Rate Variability and Autonomic Control
- Cardiovascular Disease and Adiposity
- T-cell and B-cell Immunology
- Fatty Acid Research and Health
- Atherosclerosis and Cardiovascular Diseases
- Neuroscience of respiration and sleep
- Diet, Metabolism, and Disease
- Cholesterol and Lipid Metabolism
- Cardiac Valve Diseases and Treatments
- Cardiac Ischemia and Reperfusion
University of Washington
2015-2025
University of Kansas
2025
APLA Health
2025
Seattle University
2008-2024
Children's Hospital of Orange County
2017-2024
Valley Hospital
2022-2024
Hôpital Beau-Séjour
2024
Griffin Hospital
2023
Memorial Hospital
2023
Oklahoma State University
2023
Hospital cooling improves outcome after cardiac arrest, but prehospital immediately return of spontaneous circulation may result in better outcomes.To determine whether outcomes resuscitation from arrest patients with ventricular fibrillation (VF) and without VF.A randomized clinical trial that assigned adults to standard care or cooling, accomplished by infusing up 2 L 4°C normal saline as soon possible following circulation. Adults King County, Washington, resuscitated paramedics were...
Vascular dysfunction is a major complication of metabolic disorders such as diabetes and obesity. The current studies were undertaken to determine whether inflammatory responses are activated in the vasculature mice with diet-induced obesity, if so, Toll-Like Receptor-4 (TLR4), key mediator innate immunity, contributes these responses. Mice lacking TLR4 (TLR4(-/-)) wild-type (WT) controls fed either low fat (LF) control diet or high saturated (HF) for 8 weeks. In response HF feeding, both...
Although delayed hospital cooling has been demonstrated to improve outcome after cardiac arrest, in-field started immediately the return of spontaneous circulation may be more beneficial. The aims present pilot study were assess feasibility, safety, and effectiveness cooling.We determined effect on esophageal temperature, before arrival, infusing up 2 L 4 degrees C normal saline as soon possible resuscitation from out-of-hospital arrest. A total 125 such patients randomized receive standard...
Obesity causes inflammation and insulin resistance in the vasculature as well tissues involved glucose metabolism such liver, muscle, adipose tissue. To investigate relative susceptibility of vascular tissue to these effects, we determined time course over which develops various mice with diet-induced obesity (DIO) compared tissue-based responses changes circulating inflammatory markers.Adult male C57BL/6 were fed either a control low-fat diet (LF; 10% saturated fat) or high-fat (HF, 60% for...
It has been demonstrated in rodents and humans that chronic inflammation characterized by macrophage infiltration occurs mainly adipose tissue or liver during obesity, which activation of immune cells is closely associated with insulin sensitivity. Macrophages can be classified as classically activated (M1) macrophages support microbicidal activity alternatively (M2) allergic antiparasitic responses. In the context action, M2 sustain sensitivity secreting IL-4 IL-10, while M1 induce...
Abstract Objective Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac via beneficial effects on systemic and inflammation fibrosis. Research design methods This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type diabetes (T2D) without known heart failure. Subjects were to 12 months of...
Endothelial cells release nitric oxide (NO) acutely in response to increased laminar fluid shear stress, and the increase is correlated with enhanced phosphorylation of endothelial nitric-oxide synthase (eNOS). Phosphoamino acid analysis eNOS from bovine aortic labeled [32P]orthophosphate demonstrated that only phosphoserine was present under both static flow conditions. Fluid stress induced phosphate incorporation into two specific tryptic peptides as early 30 s after initiation flow. The...
Free fatty acids (FFA) are commonly elevated in diabetes and obesity have been shown to impair nitric oxide (NO) production by endothelial cells. However, the signaling pathways responsible for FFA impairment of NO cells not characterized. Insulin receptor substrate-1 (IRS-1) regulation is critical activation synthase (eNOS) response stimulation insulin or fluid shear stress.We demonstrate that insulin-mediated tyrosine phosphorylation IRS-1 serine Akt, eNOS, significantly inhibited...
Recent clinical studies have demonstrated that mild hypothermia (32 degrees C to 34 C) induced by surface cooling improves neurological outcome after resuscitation from out-of-hospital cardiac arrest. Results animal models suggest the effectiveness of could be improved if initiated as soon possible return spontaneous circulation. Infusion cold, intravenous fluid has been proposed a safe, effective, and inexpensive technique induce arrest.In 17 hospitalized survivors arrest, we determined...
Objective— We investigated whether NADPH oxidase–dependent production of superoxide contributes to activation NF-κB in endothelial cells by the saturated free fatty acid palmitate. Methods and Results— After incubation human with palmitate at a concentration known induce cellular inflammation (100 μmol/L), we measured levels using electron spin resonance spectroscopy trap 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH). Palmitate exposure induced >2-fold increase levels,...
Abstract Recent evidence suggests that hormones such as insulin and leptin act in the hypothalamus to regulate energy balance glucose metabolism. Here we show receptor-deficient Koletsky (fak/fak) rats, adenovirally induced expression of receptors area hypothalamic arcuate nucleus improved peripheral sensitivity via enhanced suppression hepatic production, with no change insulin-stimulated uptake or disposal. This effect was associated increased signal transduction phosphatidylinositol-3-OH...
OBJECTIVE Proinflammatory activation of Kupffer cells is implicated in the effect high-fat feeding to cause liver insulin resistance. We sought determine whether reduced endothelial nitric oxide (NO) signaling contributes increase hepatic inflammatory and if so, this 1) involves 2) ameliorated by increased NO signaling. RESEARCH DESIGN AND METHODS Effect NO/cGMP on inflammation isolated was examined C57BL/6 mice, eNos−/− Vasp−/− mice fed a low-fat or diet. RESULTS show that induces...
Endothelial nitric oxide (NO) signaling plays a physiological role in limiting obesity-associated insulin resistance and inflammation. This study was undertaken to investigate whether this NO effect involves polarization of macrophages toward an anti-inflammatory M2 phenotype. Mice with transgenic endothelial synthase overexpression were protected against high-fat diet (HFD)-induced hepatic inflammation resistance, associated reduced proinflammatory M1 increased activation Kupffer cells. In...
Endothelial cells release nitric oxide (NO) acutely in response to increased “flow” or fluid shear stress (FSS), and the increase NO production is correlated with enhanced phosphorylation activation of endothelial synthase (eNOS). Both vascular growth factor FSS activate protein kinase B (PKB) by way incompletely understood pathway(s), and, turn, PKB phosphorylates eNOS at Ser-1179, causing its activation. In this study, we found that either insulin stimulated receptor substrate-1 (IRS-1)...
Comparisons of responses various cell types to excess nutrients are yielding patterns that may provide insight into the causes and consequences obesity.
Objective: To evaluate whether implementation of a therapeutic hypothermia protocol on arrival in community hospital improved survival and neurologic outcomes patients initially found to have ventricular fibrillation, pulseless electrical activity, or asystole, then successfully resuscitated from out-of-hospital cardiac arrest. Design: A retrospective study who presented after compared with those before the was implemented. Setting: Harborview Medical Center, Seattle, WA. Patients: total 491...
Hematopoietic stem cells (HSCs) maintain blood homeostasis and are the functional units of bone marrow transplantation. To improve molecular understanding HSCs their proximal progenitors, we performed transcriptome analysis within context ImmGen Consortium data set. Gene sets that define steady-state mobilized HSCs, as well hematopoietic progenitor (HSPCs), were determined. Genes involved in transcriptional regulation, including a group putative repressors, identified multipotent progenitors...
Diet-induced obesity (DIO) in mice causes vascular inflammation and insulin resistance that are accompanied by decreased endothelial-derived NO production. We sought to determine whether reduced NO-cGMP signaling contributes the deleterious effects of DIO on vasculature and, if so, these can be blocked increased signaling.By using an established endothelial cell culture model resistance, exposure palmitate, 100 micromol/L, for 3 hours induced both cellular (activation IKK beta-nuclear...
Intake of trans fatty acids (TFA), which are consumed by eating foods made from partially hydrogenated vegetable oils, is associated with a higher risk cardiovascular disease. This relation can be explained many factors including TFA's negative effect on endothelial function and reduced nitric oxide (NO) bioavailability. In this study we investigated the effects three different TFA (2 common isomers C18 found in oil isomer ruminant-derived—dairy products meat) NF-κB activation production....
Obesity is characterized by chronic inflammation of adipose tissue, which contributes to insulin resistance and diabetes. Although nitric oxide (NO) signaling has antiinflammatory effects in the vasculature, whether reduced NO tissue unknown. We sought determine (1) obesity induced high-fat (HF) diet reduces endothelial (2) synthase (eNOS) sufficient induce independent diet, (3) increased cGMP can block HF feeding.Relative mice fed a low-fat an markedly phospho-eNOS...