Prevalence, Management, and Comorbidities of Adults With Atrial Fibrillation in the United States, 2019 to 2023.

Background: Due to evolving risk factor profiles and an aging population, atrial fibrillation poses a significant public health challenge in the United States. Therefore, a contemporary and nationally representative epidemiological study is necessary to reassess atrial fibrillation's impact on the health care system.

Objectives: The purpose of the study was to provide the most current and detailed assessment of atrial fibrillation's prevalence and management in the United States.

Polymeric Micellar Nanoparticles Enable Image-guided Drug Delivery in Solid Tumors.

We report the development of a nanotechnology to co-deliver chemocoxib A with a reactive oxygen species (ROS)-activatable and COX-2 targeted pro-fluorescent probe, fluorocoxib Q (FQ) enabling real time visualization of COX-2 and CA drug delivery into solid cancers, using a di-block PPS - -POEGA copolymer, selected for its intrinsic responsiveness to elevated reactive oxygen species (ROS), a key trait of the tumor microenvironment. FQ and CA were synthesized independently, then co-encapsulated within micellar PPS - -POEGA co-polymeric nanoparticles (FQ-CA-NPs), and were assessed for cargo concentration, hydrodynamic diameter, zeta potential, and ROS-dependent cargo release. The uptake of FQ-CA-NPs in mouse mammary cancer cells and cargo release was assessed by fluorescence microscopy.

Discovery of a Redox-Activatable Chemical Probe for Detection of Cyclooxygenase-2 in Cells and Animals.

Cyclooxygenase-2 (COX-2) expression is up-regulated in inflammatory tissues and many premalignant and malignant tumors. Assessment of COX-2 protein in vivo, therefore, promises to be a powerful strategy to distinguish pathologic cells from normal cells in a complex disease setting. Herein, we report the first redox-activatable COX-2 probe, fluorocoxib Q (FQ), for in vivo molecular imaging of pathogenesis.

Molecular Imaging of Inflammation in Osteoarthritis Using a Water-Soluble Fluorocoxib.

Clinical imaging approaches to detect inflammatory biomarkers, such as cyclooxygenase-2 (COX-2), may facilitate the diagnosis and therapy of inflammatory diseases. To this end, we report the discovery of -[(rhodamin-X-yl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1-indol-3-yl]acetamide chloride salt (fluorocoxib D), a hydrophilic analog of fluorocoxib A. Fluorocoxib D inhibits COX-2 selectively in purified enzyme preparations and cells.

Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children.

The atypical antipsychotic risperidone (RSP) is often associated with weight gain and cardiometabolic side effects. The mechanisms for these adverse events are poorly understood and, undoubtedly, multifactorial in etiology. In light of growing evidence implicating the gut microbiome in the host's energy regulation and in xenobiotic metabolism, we hypothesized that RSP treatment would be associated with changes in the gut microbiome in children and adolescents.

Cardiovascular, metabolic, and coronary dysfunction in high-fat-fed obesity-resistant/prone rats.

Objective: Obesity is a global epidemic leading to several comorbidities including diabetes and cardiovascular disease. The hypothesis that the genetic background of the obesity-prone rat (OP) predisposes to physiologic, metabolic, and microvascular dysfunction which is exacerbated by a diet high in saturated fats was tested.

Methods: Male OP and obesity-resistant (OR) rats were fed either a diet containing 10% (chow) or 45% kcal fat (HF) for 42 weeks.

Characterization of diabetic neuropathy in the Zucker diabetic Sprague-Dawley rat: a new animal model for type 2 diabetes.

Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco) was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats.

Progression and reversal of coronary and mesenteric vascular dysfunction associated with obesity.

Objective: The purpose of this study was to examine progression and reversal of microvascular complications when rats were fed a high fat diet.

Methods: Sprague-Dawley rats 10 weeks of age were fed a diet containing 45% kcal fat for up to 32 weeks. Blood pressure and heart rate was measured by telemetry.

Dietary fat, fatty acid saturation and mitochondrial bioenergetics.

Fat intake alters mitochondrial lipid composition which can affect function. We used novel methodology to assess bioenergetics, including simultaneous ATP and reactive oxygen species (ROS) production, in liver and heart mitochondria of C57BL/6 mice fed diets of variant fatty acid content and saturation. Our methodology allowed us to clamp ADP concentration and membrane potential (ΔΨ) at fixed levels.

Modification of high saturated fat diet with n-3 polyunsaturated fat improves glucose intolerance and vascular dysfunction.

Aims: The ability of dietary enrichment with monounsaturated fatty acid (MUFA), n-3 or n-6 polyunsaturated fatty acids (PUFAs) to reverse glucose intolerance and vascular dysfunction resulting from excessive dietary saturated fatty acids is not resolved. We hypothesized that partial replacement of dietary saturated fats with n-3 PUFA-enriched menhaden oil (MO) would provide greater improvement in glucose tolerance and vascular function compared to n-6 enriched safflower oil (SO) or MUFA-enriched olive oil (OO).

Methods: We fed mice a high saturated fat diet (HF) (60% kcal from lard) for 12 weeks before substituting half the lard with MO, SO or OO for an additional 4 weeks.

Role of the effect of inhibition of neutral endopeptidase on vascular and neural complications in streptozotocin-induced diabetic rats.

We have previously shown that treating streptozotocin-induced diabetic rats, an animal model of type 1 diabetes, with Ilepatril (an inhibitor of neutral endopeptidase and angiotensin converting enzyme (ACE)) improves vascular and neural function. In this study we sought to determine the individual effect of inhibition of neutral endopeptidase and ACE on diabetes-induced vascular and neural dysfunction. After 4 weeks of untreated diabetes, rats were treated for 12 weeks with Ilepatril, Enalapril (ACE inhibitor) or Candoxatril (neutral endopeptidase inhibitor) followed by analysis of neural and vascular function.

Diet-induced obesity in Sprague-Dawley rats causes microvascular and neural dysfunction.

Background: The objective of this study was to determine the effect of diet-induced obesity (DIO) on microvascular and neural function.

Methods: Rats were fed a standard or high fat diet for up to 32 weeks. The following measurements were carried out: vasodilation in epineurial arterioles using videomicroscopy, endoneurial blood flow using hydrogen clearance, nerve conduction velocity using electrical stimulation, size-frequency distribution of myelinated fibres of the sciatic nerve, intraepidermal nerve fibre density using confocal microscopy and thermal nociception using the Hargreaves method.

Vascular and neural dysfunctions in obese Zucker rats: effect of AVE7688.

The purpose of this study was to determine whether AVE7688 a drug that inhibits both angiotensin converting enzyme and neutral endopeptidase activity protects vascular and nerve functions in an animal model of metabolic syndrome. Obese Zucker rats at 20 weeks of age were treated for 12 weeks with AVE7688. Vasodilation in epineurial arterioles was measured by videomicroscopy and nerve conduction velocity was measured following electrical stimulation.

Treatment of Zucker diabetic fatty rats with AVE7688 improves vascular and neural dysfunction.

Aim: Vasopeptidase inhibitors are drugs that inhibit angiotensin-converting enzyme and neutral endopeptidase (NEP). The latter is a protease that degrades vasoactive peptides and is increased in diabetes. We have previously shown that treating streptozotocin-induced diabetic rats, an animal model of type 1 diabetes, with AVE7688, a vasopeptidase inhibitor, improves neurovascular and neural function.

Attenuation of vascular/neural dysfunction in Zucker rats treated with enalapril or rosuvastatin.

Objective: Obese Zucker rats, animal model for the metabolic syndrome, develop a diabetes-like neuropathy that is independent of hyperglycemia. The purpose of this study was to determine whether drugs used to treat cardiovascular dysfunction in metabolic syndrome also protect nerve function.

Methods And Procedures: Obese Zucker rats at 20 weeks of age were treated for 12 weeks with enalapril or rosuvastatin.

Treatment of cardiovascular dysfunction associated with the metabolic syndrome and type 2 diabetes.

Unlabelled: Our previous studies have shown vascular dysfunction in small coronary and mesenteric arteries in Zucker obese rats, a model of the metabolic syndrome, and Zucker Diabetic Fatty (ZDF) rats, a model of type 2 diabetes. Because of their lipid lowering action and antioxidant activity, we predicted that treatment with Rosuvastatin, an HMG-CoA reductase inhibitor (statin) or Enalapril, an angiotensin converting enzyme (ACE) inhibitor would improve vascular dysfunction associated with the metabolic syndrome and type 2 diabetes.

Methods: 20-week-old Zucker obese and 16-week-old ZDF rats were treated with Rosuvastatin (25 mg/kg/day) or Enalapril (20 mg/kg/day) for 12 weeks.

Vascular and neural dysfunction in Zucker diabetic fatty rats: a difficult condition to reverse.

Aim: We had previously demonstrated that vascular and neural dysfunction in Zucker diabetic fatty (ZDF) rats is progressive. In this study, we sought to determine whether monotherapy of ZDF rats can reverse the vascular and nerve defects.

Methods: ZDF rats at 16 weeks of age were treated for 12 weeks with the angiotensin-converting enzyme inhibitor enalapril, the antioxidant alpha-lipoic acid, the HMG-CoA reductase inhibitor rosuvastatin or the PPARgamma agonist rosiglitazone.

Role of nitrosative stress in early neuropathy and vascular dysfunction in streptozotocin-diabetic rats.

Evidence for important roles of the highly reactive oxidant peroxynitrite in diabetic complications is emerging. We evaluated the role of peroxynitrite in early peripheral neuropathy and vascular dysfunction in STZ-diabetic rats. In the first dose-finding study, control and STZ-diabetic rats were maintained with or without the potent peroxynitrite decomposition catalyst Fe(III)tetrakis-2-(N-triethylene glycol monomethyl ether) pyridyl porphyrin (FP15) at 3, 5, or 10 mg.

Treatment of streptozotocin-induced diabetic rats with AVE7688, a vasopeptidase inhibitor: effect on vascular and neural disease.

In epineurial arterioles, acetylcholine-mediated vascular relaxation is mediated by nitric oxide and endothelium-derived hyperpolarizing factor (EDHF), and both mechanisms are impaired by diabetes. The mediator responsible for the effect of EDHF is unknown. In epineurial arterioles, C-type natriuretic peptide (CNP) has properties consistent with EDHF-like activity.

Progression of coronary and mesenteric vascular dysfunction in Zucker obese and Zucker diabetic fatty rats.

We investigated the progression of vascular dysfunction associated with the metabolic syndrome with and without hyperglycemia in lean, Zucker obese, and Zucker diabetic fatty (ZDF) rats. Responses of aorta and small coronary and mesenteric arteries were measured to endothelium-dependent and -independent vasodilators. Indices of oxidative stress were increased in serum from ZDF rats throughout the study, whereas values were increased in Zucker obese rats later in the study [thiobarbituric acid reactive substances: 0.

ACE inhibitor or angiotensin II receptor antagonist attenuates diabetic neuropathy in streptozotocin-induced diabetic rats.

ACE inhibition and/or blocking of the angiotensin II receptor are recognized as first-line treatment for nephropathy and cardiovascular disease in diabetic patients. However, little information is available about the potential benefits of these drugs on diabetic neuropathy. We examined vascular and neural activity in streptozotocin-induced diabetic rats that were treated for 12 weeks with enalapril, an ACE inhibitor, or L-158809, an angiotensin II receptor blocker.

Progression of vascular and neural dysfunction in sciatic nerves of Zucker diabetic fatty and Zucker rats.

We have examined the progression of vascular and neural deficits in Zucker rats, Zucker diabetic fatty (ZDF) diabetic rats, and age-matched lean ZDF rats from 8 to 40 wk of age. Both the ZDF diabetic and Zucker rats were glucose intolerant at 8 wk of age. The Zucker rats did not become hyperglycemic but were hyperinsulinemic through 32 wk of age.

20-hydroxyeicosatetraenoic acid (20-HETE) metabolism in coronary endothelial cells.

We have investigated the role of endothelial cells in the metabolism of 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoactive mediator synthesized from arachidonic acid by cytochrome P450 omega-oxidases. Porcine coronary artery endothelial cells (PCEC) incorporated 20-[(3)H]HETE primarily into the sn-2 position of phospholipids through a coenzyme A-dependent process. The incorporation was reduced by equimolar amounts of arachidonic, eicosapentaenoic or 8,9-epoxyeicosatrienoic acids, but some uptake persisted even when a 10-fold excess of arachidonic acid was available.

Coronary vascular dysfunction associated with direct current shock injury.

Objective: To determine if cardiac injury following DC shocks includes impairment of coronary vascular reactivity.

Methods: 36 dogs (18-32 kg) were anesthetized and a thoracotomy was performed. Either antioxidant enzymes, superoxide dismutase (SOD, 15,000 U/kg) plus catalase (55,000 U/kg) or the NO synthase inhibitor N(G)-nitro-L-arginine (L-NNA, 5 mg/kg) was administered IV prior to sham (no shocks) or DC shock treatment, and the results were compared to dogs which did not receive SOD/catalase or L-NNA.