A5082862007- Stress Responses and Cortisol
- Nitric Oxide and Endothelin Effects
- Adipose Tissue and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Acute Ischemic Stroke Management
- Neurological Disease Mechanisms and Treatments
- Heart Rate Variability and Autonomic Control
- Hormonal Regulation and Hypertension
- Hemoglobinopathies and Related Disorders
- Cardiovascular and exercise physiology
- Mosquito-borne diseases and control
- Tryptophan and brain disorders
- Cardiovascular Disease and Adiposity
- High Altitude and Hypoxia
- Cardiac Health and Mental Health
- COVID-19 Clinical Research Studies
- Hemoglobin structure and function
- Receptor Mechanisms and Signaling
- Cardiovascular Health and Disease Prevention
- SARS-CoV-2 and COVID-19 Research
- Erythropoietin and Anemia Treatment
- Cerebrovascular and Carotid Artery Diseases
- Diet and metabolism studies
- Muscle metabolism and nutrition
- Vector-borne infectious diseases
National Institute of Allergy and Infectious Diseases
2018-2024
National Institutes of Health
2019-2023
Vector (United States)
2019-2021
West Virginia University
2013-2018
National Heart Lung and Blood Institute
2018
American Academy of Ophthalmology
2017
West Virginia University Hospitals
2013-2015
Brooks Automation (Germany)
2013
Providence Hospital
2005
University of Pittsburgh
2004
PARRY-BILLINGS, M., R. BUDGETT, Y. KOUTEDAKIS, E. BLOMSTRAND, S. BROOKS, C. WILLIAMS, P. CALDER, PILLING, BAIGRIE, and A. NEWSHOLME. Plasma amino acid concentrations in the overtraining syndrome: possible effects on immune system. Med. Sci. Sports Exerc., Vol. 24, No. 12, pp. 1353–1358, 1992. Overtraining long-term exercise are associated with an impairment of function. We provide evidence support hypothesis that supply glutamine, a key fuel for cells system, is impaired these conditions...
Objective Immune dysregulation influences outcome following acute ischemic stroke (AIS). Admission white blood cell (WBC) counts are routinely obtained, making the neutrophil–lymphocyte ratio (NLR) a readily available biomarker of immune response to stroke. This study sought identify relationship between NLR and 90 day AIS outcome. Methods A retrospective analysis was performed on patients who underwent endovascular therapy for at West Virginia University Hospitals, Morgantown, Virginia. WBC...
Chronic, unresolved stress is a major risk factor for the development of clinical depression. While many preclinical models stress-induced depression have been reported, unpredictable chronic mild (UCMS) protocol an established translationally-relevant model inducing behavioral symptoms commonly associated with depression, such as anhedonia, altered grooming behavior, and learned helplessness in rodents. The UCMS also induces physiological (e.g., hypercortisolemia, hypertension) neurological...
Chronic presentation of the MS is associated with an increased likelihood for stroke and poor outcomes following occlusive cerebrovascular events. However, physiological mechanisms contributing to compromised remain unclear, degree cerebral cortical MVD may represent a central determinant outcomes.
The presence of chronic, unresolvable stresses leads to negative health outcomes, including development clinical depression/depressive disorders, with outcome severity being correlated depressive symptom severity. One the major outcomes associated chronic stress and depression is cardiovascular disease (CVD) an elevated CVD risk profile. However, in epidemiological research, sex disparities are evident, premenopausal women suffering from symptoms more acutely than men, but also demonstrating...
The metabolic syndrome (MetS) is highly prevalent in the North American population and associated with increased risk for development of cerebrovascular disease. This study determined structural functional changes middle cerebral arteries (MCA) during progression MetS effects chronic pharmacological interventions on mitigating vascular alterations obese Zucker rats (OZR), a translationally relevant model MetS. reactivity wall mechanics ex vivo pressurized MCA from lean (LZR) OZR were at 7-8,...
Abstract Resistance artery vasodilation in response to hypoxia is essential for matching tissue oxygen and demand. In hypoxia, erythrocytic hemoglobin tetramers produce nitric oxide through nitrite reduction. We hypothesized that the alpha subunit of expressed endothelium also facilitates reduction proximal smooth muscle. Here, we create two mouse strains test this: an endothelial-specific globin knockout (EC Hba1Δ/Δ) another with allele mutated prevent globin’s inhibitory interaction...
Saliva from mosquitoes contains vasodilators that antagonize vasoconstrictors produced at the bite site. Sialokinin is a vasodilator present in saliva of Aedes aegypti. Here, we investigate its function and describe mechanism action during blood feeding. induces nitric oxide release similar to substance P. Sialokinin-KO produce lower perfusion than parental site probing have significantly longer times, which result feeding success. In contrast, there no difference between KO when using...
The increasing prevalence and severity of clinical depression are strongly correlated with vascular disease risk, creating a comorbid condition poor outcomes but demonstrating sexual disparity whereby female subjects at lower risk than male for subsequent cardiovascular events. To determine the potential mechanisms responsible this protection against stress/depression-induced vasculopathy in subjects, we exposed male, intact female, ovariectomized (OVX) lean Zucker rats to unpredictable...
To determine the impact of progressive elevations in peripheral vascular disease (PVD) risk on microvascular function, we utilized eight rat models spanning "healthy" to "high PVD risk" and used a multiscale approach interrogate function outcomes: healthy: Sprague-Dawley rats (SDR) lean Zucker (LZR); mild risk: SDR high-salt diet (HSD) high-fructose (HFD); moderate reduced renal mass-hypertensive (RRM) spontaneously hypertensive (SHR); high obese (OZR) Dahl salt-sensitive (DSS). Vascular...
What is the central question of this study? How does chronic stress impact cerebrovascular function and metabolic syndrome accelerate adaptations to stress? role exercise training have in preventing changes syndrome? main finding its importance? Stressful conditions lead pathological cerebrovasculature via an oxidative nitric oxide pathway, presence produces a greater susceptibility stress-induced dysfunction. The results also provide insight into mechanisms that may contribute influence...
Objectives: The objectives of this study were to determine the change in gene expression between two time points following stroke and identify biomarkers recovery through profiling pathway analysis. Methods: Peripheral blood was collected from 34 ischemic patients (confirmed by magnetic resonance imaging) ≥18 years age, within 24 hr symptom onset 24–48 later, healthy controls. Modified Rankin Scale (MRS) used 30-day recovery. Total RNA extracted whole Paxgene tubes, amplified, hybridized...
Aedes aegypti saliva facilitates blood meal acquisition through pharmacologically active compounds that prevent host hemostasis. Among these salivary proteins are the D7s, which highly abundant and have been shown to act as scavengers of biogenic amines eicosanoids. In this work, we performed comparative structural modeling, characterized binding capabilities, assessed physiological functions Ae. protein AeD7L2 compared well-characterized AeD7L1. AeD7L1 show different affinities several...
To successfully feed on blood, hematophagous arthropods must combat the host's natural hemostatic and inflammatory responses. Salivary proteins of blood-feeding insects such as mosquitoes contain compounds that inhibit these common host defenses against blood loss, including vasoconstriction, platelet aggregation, clotting, pain, itching. The D7 are some most abundantly expressed in female mosquito salivary glands have been implicated inhibiting Anopheles gambiae, primary vector malaria,...
Angiotensin-converting enzyme 2 (ACE2) is the established cellular receptor for SARS-CoV-2. However, it unclear whether ACE1 inhibitors (e.g., lisinopril) or angiotensin blockers losartan) alter tissue ACE2 expression. This study sought to determine lisinopril losartan, as monotherapies in combination, changes levels of healthy male and female mice. Mice received (10 mg/kg/day), losartan both 21 days via drinking water. A control group water without drug. The protein index (ACE2...
Background— Conduction system defects and slowed ventricular conduction are common in patients with systolic dysfunction contribute to arrhythmias sudden death. In animal models of heart failure, cardiac α 1 -adrenergic signaling is constitutively activated. Here, we report the effects constitutive activation on connexin phosphorylation conduction. Methods Results— Transgenic mice were generated cardiac-specific overexpression transcription factor RTEF-1 (transcription enhancer...
Abstract Objective To determine H MV and PS in skeletal muscle of OZR evaluate the impact increased microvascular perfusion heterogeneity on mass transport/exchange. Methods The situ gastrocnemius from LZR was examined under control conditions following pretreatment with TEMPOL (antioxidant)/ SQ ‐29548 ( PGH 2 /TxA receptor antagonist), phentolamine (adrenergic or all agents combined. A spike input a labeled blood tracer cocktail injected into perfusing artery. Tracer washout analyzed using...
While it is known that chronic stress and clinical depression are powerful predictors of poor cardiovascular outcomes, recent evidence has identified correlations between the development metabolic disease depressive symptoms, creating a combined condition severely elevated risk. In this study, we used obese Zucker rat (OZRs) unpredictable mild (UCMS) model to determine impact preexisting on relationship stress/depressive symptoms vascular function. Additionally, determined syndrome sex-based...
Chronic, unresolved stress is a major risk factor for the development of clinical depression. While many preclinical models stress-induced depression have been reported, unpredictable chronic mild (UCMS) protocol an established translationally-relevant model inducing behavioral symptoms commonly associated with depression, such as anhedonia, altered grooming behavior, and learned helplessness in rodents. The UCMS also induces physiological (e.g., hypercortisolemia, hypertension) neurological...
BACKGROUND: Severe malaria is associated with impaired nitric oxide (NO) synthase (NOS)–dependent vasodilation, and reversal of this deficit improves survival in murine models. Malaria might have selected for genetic polymorphisms that increase endothelial NO signaling now contribute to heterogeneity vascular function among humans. One protein potentially alpha globin, which, mouse models, interacts NOS (eNOS) negatively regulate signaling. We sought evaluate the impact globin gene deletions...
Abstract Background Babesia rossi is a leading cause of morbidity and mortality among the canine population sub-Saharan Africa, but pathogenesis remains poorly understood. Previous studies B. infection were derived from clinical cases, in which neither onset nor infectious inoculum was known. Here, we performed controlled inoculations canines evaluated disease progression through tests whole blood transcriptomic profiling. Results Two subjects administered low (10 4 parasites) while three...
Abstract Objective Many types of vascular smooth muscle cells exhibit prominent K DR currents. These currents may be mediated, at least in part, by V 1.5 channels, which are sensitive to inhibition DPO ‐1. We tested the hypothesis that ‐1‐sensitive channels regulate tone and reactivity resistance‐sized vessels from rat brain ( MCA ) skeletal GA ). Methods Middle cerebral gracilis arteries were isolated subjected three kinds experimental analysis: (i) western blot/immunocytochemistry; (ii)...
The study of peripheral vasculopathy with chronic metabolic disease is challenged by divergent contributions from spatial (the level resolution or specific tissue being studied) and temporal origins (evolution the developing impairments in time). Over many years studying development skeletal muscle its functional implications, we may be at point presenting an integrated conceptual model that addresses these challenges within obese Zucker rat (OZR) model. At early stages disease, where...