A5008709402- Cardiac Ischemia and Reperfusion
- Diet and metabolism studies
- Cardiovascular Health and Disease Prevention
- Receptor Mechanisms and Signaling
- Adipose Tissue and Metabolism
- Neuropeptides and Animal Physiology
- Cardiac Arrest and Resuscitation
- Cardiac electrophysiology and arrhythmias
- Blood Pressure and Hypertension Studies
- Metabolism, Diabetes, and Cancer
- Fatty Acid Research and Health
- Cardiovascular Function and Risk Factors
- Cardiovascular Disease and Adiposity
- Pharmacology and Obesity Treatment
- Renin-Angiotensin System Studies
- Apelin-related biomedical research
- Physiological and biochemical adaptations
- Venous Thromboembolism Diagnosis and Management
- Heart Rate Variability and Autonomic Control
- Peroxisome Proliferator-Activated Receptors
- Blood Coagulation and Thrombosis Mechanisms
- Sympathectomy and Hyperhidrosis Treatments
- Adenosine and Purinergic Signaling
- Protein Hydrolysis and Bioactive Peptides
- Congenital Heart Disease Studies
Pfizer (United States)
2000-2025
Brigham Young University
2019-2025
Johns Hopkins All Children's Hospital
2024
Johns Hopkins University
2024
Smith Family
2011
King's College London
2004-2008
Novartis (Switzerland)
2008
Guy's Hospital
2005
St Thomas' Hospital
1998-2004
ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), the phase 3 morbidity and mortality trial torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, identified previously undescribed changes plasma levels potassium, sodium, bicarbonate, aldosterone. A key question after this is whether failure torcetrapib was result CETP inhibition or some other pharmacology molecule. The direct effects related molecules on adrenal steroid...
Increased arterial stiffness, as estimated from aortic pulse wave velocity (Ao-PWV), and albuminuria are independent predictors for cardiovascular disease in type 2 diabetes mellitus (T2DM). Whether angiotensin receptor blockers (ARBs), drugs with cardio-renal protective effects, improve Ao-PWV to a greater extent than other equipotent antihypertensive medications remains unclear. After 4-week washout phase, we compared the effects of valsartan (n=66), an ARB, that amlodipine (n=65), calcium...
Development of microalbuminuria increases the risk for cardiovascular disease (CVD) in type 2 diabetes. The nature this relationship is unclear but may involve arterial stiffness, an independent marker CVD mortality. Aortic pulse wave velocity (Ao-PWV) and albumin creatinine ratio (ACR) were measured 134 consecutive patients with diabetes without overt renal impairment (serum <150 micromol/L). ACR ranged from 0.2 to 153 mg/mmol. Patients raised (>/=3 mg/mmol) had higher Ao-PWV, poorer...
Hypertension and type 2 diabetes are associated with increased aortic pulse wave velocity (PWV), a measure of stiffness powerful risk factor for cardiovascular events. The association hypertension may obscure the degree to which rather than contributes an elevated PWV. objective this study was determine whether presence is PWV compared nondiabetic subjects matched mean arterial blood pressure. determined by measuring carotid femoral transit time using applanation tonometry in 186 (104 women)...
The aim was to establish a method for measuring organ blood flow in rats using commercially available, coloured, dye extraction microspheres.A mixture of radiolabelled and microspheres infused into at rest (basal) during intravenous administration either angiotensin II (0.5 microgram.kg-1.min-1) or isoprenaline [12.5 ng.(g0.74)-1.min-1]. Tissues were removed placed test tubes, counted radioactivity, then digested with 2N sodium hydroxide. Within the same tube, isolated centrifugation...
Abstract Sarcopenia refers to the decline in muscle mass and function that occurs with advancing age. It is driven by alterations multiple cellular processes. AMP‐activated protein kinase (AMPK) a energy sensor opposes many age‐related changes, making it an attractive target for treatment of sarcopenia. This study aimed test effect chronic old mice AMPK‐activating prodrug, AICAR, on treadmill running capacity mass, force production, gene expression, intracellular markers relevant Old (23...
Abstract PF-08046037 (formerly known as SGN-PDL1iT) is an immune-stimulating antibody conjugate (ISAC) designed to induce immune response against cancer cells by delivering a potent Toll-like receptor 7 (TLR7) agonist tumor associated antigen-presenting (APCs) expressing PD-L1. The ISAC consists of anti-PD-L1 linked imidazoquinoline-based TLR7 using mannosidase-cleavable maleimidopropionyl-mannose linker (mp-mann). Upon binding PD-L1 on APCs, internalizes and releases the payload into...
The cardioprotective efficacy of zoniporide (CP-597,396), a novel, potent, and selective inhibitor the sodium-hydrogen exchanger isoform 1 (NHE-1), was evaluated both in vitro vivo using rabbit models myocardial ischemia-reperfusion injury. In these models, injury elicited with 30 min regional ischemia 120 reperfusion. Zoniporide concentration-dependent reduction infarct size (EC(50) 0.25 nM) isolated heart (Langendorff) reduced by 83% (50 nM). This compound 2.5- to 20-fold more potent than...
Abstract Hypoplastic left heart syndrome (HLHS) is a congenital malformation commonly treated with palliative surgery and associated significant morbidity mortality. Risk stratification models have often relied upon traditional survival analyses or outcomes data failing to extend beyond infancy. Individualized prediction of transplant-free (TFS) employing machine learning (ML) based infancy may provide further valuable insight for families healthcare providers along the course staged...
Interventions such as glycogen depletion, which limit myocardial anaerobic glycolysis and the associated proton production, can reduce ischemic injury; thus it follows that inhibition of glycogenolysis should also be cardioprotective. Therefore, we examined whether novel phosphorylase inhibitor 5-Chloro-N-[(1S,2R)-3-[(3R,4S)-3,4-dihydroxy-1-pyrrolidinyl)]-2-hydroxy-3-oxo-1-(phenylmethyl)propyl]-1H-indole-2-carboxamide (ingliforib; CP-368,296) could infarct size in both vitro vivo rabbit...
Preclinical and clinical data suggest that acetyl-CoA carboxylase (ACC) inhibitors have the potential to rebalance disordered lipid metabolism, leading improvements in nonalcoholic steatohepatitis (NASH). Consistent with these observations, first-in-human trials our ACC inhibitor PF-05175157 led robust reduction of de novo lipogenesis (DNL), albeit concomitant reductions platelet count, which were attributed inhibition fatty acid synthesis within bone marrow. Herein, we describe design,...
We recently reported the identification of a novel human adenosine A3 receptor-selective agonist, (2S,3S,4R,5R)-3-amino-5-[6-[5-chloro-2-(3-methylisoxazol-5-ylmethoxy)benzylamino]purin-9-yl]-4-hydroxytetrahydrofuran-2-carboxylic acid methylamide (CP-608,039), with 1,260-fold selectivity for versus A1 receptor (DeNinno et al., J Med Chem 46: 353-355, 2003). However, because modest (20-fold) rabbit CP-608,039 precludes demonstration A3-mediated cardioprotection in models, we identified another...
This study investigated whether aldose reductase (AR) inhibition with zopolrestat, either alone or in combination an adenosine A(3)-receptor agonist (CB-MECA), reduced myocardial ischemic injury rabbit hearts subjected to 30 min of regional ischemia and 120 reperfusion. Zopolrestat infarct size by up 61%, both vitro (2 nM 1 microM; EC(50) = 24 nM) vivo (50 mg/kg). sorbitol concentration (index AR activity) >50% (control, 15.0 +/- 2.2 nmol/g; 200 6.7 1.3 nmol/g). A modestly cardioprotective...
1. The solubility of fatty acids in aqueous media containing bile salts alone and admixture with either lecithin (phosphatidylcholine) or phosphatidylethanolamine was determined. 2. Over the pH range 2-0-7-4, order acid solutions linoleic greater than oleic elaidic palmitic stearic. each increased as miceus greatly stearic acid. 4. In presence lecithin, decreased increasing micellar solution, indicating a competitive effect between anions lecithin. linearly concentration. 5....
1. The solubility of fatty acids in aqueous solutions containing bile salts and lysolecithin at pH values between 2.0 7.4 was studied. Both the 1-acyl 2-acyl isomers increased to same extent, order being linoleic > oleic elaidic palmitic stearic. 2. influence products phospholipolysis lecithin on acid determined. On a molar basis, more effective than were promoting solubilization acid. 3. In salt which phospholipid concentration constant decreased linearly with progressive replacement by...
Recent evidence from our laboratory and others suggests that nitric oxide (NO) is a modulator of in vivo vitro oxygen consumption the murine canine heart. Therefore, goal study was twofold: to determine whether NO modulates myocardial nonhuman primate heart evaluate seemingly cardioprotective actions amlodipine may involve an NO-mediated mechanism. Using Clark-type O 2 electrode, we measured cynomologous monkey at baseline after increasing doses S-nitroso- N-acetylpenicillamine (SNAP; 10 −7...
Abstract Background Endothelium-dependent flow mediated dilation (FMD) and pulse-wave velocity (PWV), are used as measures of vascular health predictors cardiovascular risk in clinical studies, both age-dependent. Numbers circulating endothelial microparticles (EMPs) progenitor cells (EPCs) also associated with risk, but independent age humans. The use these measurements for pre-clinical assessment drug safety efficacy non-human primates (NHPs) may promote the translation drug-induced...
A ketogenic diet (KD) has been proposed as a treatment for many conditions including obesity, diabetes, epilepsy, and Parkinson's Disease. Various studies have shown its effects on health lifespan in model organisms suggesting that it is beneficial individuals. Some concern exists KD might negatively impact anabolic signaling through the mTOR pathway, but molecular of remain largely unexplored, particularly skeletal muscle. The purpose this study, therefore, was to determine how affects...