A5000658643- Nitric Oxide and Endothelin Effects
- Hemoglobin structure and function
- Blood transfusion and management
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Cellular Mechanics and Interactions
- Erythrocyte Function and Pathophysiology
- Adipose Tissue and Metabolism
- Organ Transplantation Techniques and Outcomes
- Respiratory Support and Mechanisms
- S100 Proteins and Annexins
- Neonatal Respiratory Health Research
- Hemodynamic Monitoring and Therapy
- Neuroinflammation and Neurodegeneration Mechanisms
- Nosocomial Infections in ICU
- Neuroscience of respiration and sleep
- Eicosanoids and Hypertension Pharmacology
- Electrolyte and hormonal disorders
- Renin-Angiotensin System Studies
- Heme Oxygenase-1 and Carbon Monoxide
- Intensive Care Unit Cognitive Disorders
- Cystic Fibrosis Research Advances
- Burn Injury Management and Outcomes
- Electron Spin Resonance Studies
- Phosphodiesterase function and regulation
- Pharmacology and Obesity Treatment
University of Alabama at Birmingham
2010-2024
University of Tennessee Health Science Center
2011
Chronic wounds have a large impact on health, affecting ∼6.5 M people and costing ∼$25B/year in the US alone [1]. We previously discovered that genetically modified mouse model displays impaired healing similar to problematic humans sometimes become chronic. Here we show how why these chronic, describe way whereby can drive chronicity at will propose same processes are involved chronic wound development humans. hypothesize exacerbated levels of oxidative stress critical for initiation...
Storage of erythrocytes in blood banks is associated with biochemical and morphological changes to RBCs (red cells). It has been suggested that these have potential negative clinical effects characterized by inflammation microcirculatory dysfunction which add other transfusion-related toxicities. However, the mechanisms linking RBC storage toxicity remain unclear. In present study we tested hypothesis leucodepleted results cells inhibit NO (nitric oxide) signalling more so than younger...
Background Trauma is the leading cause of death and disability in patients aged 1–46 y. Severely injured experience considerable blood loss hemorrhagic shock requiring treatment with massive transfusion red cells (RBCs). Preclinical retrospective human studies trauma have suggested that poorer therapeutic efficacy, increased severity organ injury, bacterial infection are associated large volumes stored RBCs, although mechanisms not fully understood. Methods findings We developed a murine...
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Acyloxy nitroso compounds hydrolyze to nitroxyl (HNO), a nitrogen monoxide with distinct chemistry and biology. Ultraviolet−visible spectroscopy mass spectrometry show hydrolysis rate depends on pH ester group structure the observed being trifluoroacetate (3) > acetate (1) pivalate (2). Under all conditions, 3 rapidly hydrolyzes HNO. A combination of spectroscopic, kinetic, product studies that addition thiols increases decomposition 1 2, leading conditions favor thiolates, thiolate directly...
The erythrocyte is proposed to play a key role in the control of local tissue perfusion via three O 2 -dependent signaling mechanisms: 1) reduction circulating nitrite vasoactive NO, 2) S-nitrosohemoglobin (SNO-Hb)-dependent vasodilatation, and 3) release vasodilator sympatholytic ATP; however, their relative roles vivo remain unclear. Here we evaluated each mechanism gain insight into regulation human skeletal muscle blood flow during hypoxia hyperoxia at rest exercise. Arterial femoral...
Diabetic foot ulcers, although associated with macrovascular disease and neuropathy, have a microvascular causing ischemia not amenable to surgical intervention. Nitrite selectively releases nitric oxide in ischemic tissues, diabetes subjects low nitrite levels that do increase exercise. This study explores the safety pharmacokinetics of single dose sodium diabetic ulcers.Using blinded, randomized crossover design, 12 mellitus active or healed ulcers received on two occasions 7-28 days...
Decreases in endothelial nitric oxide synthase derived (NO) production during liver transplantation promotes injury. We hypothesized that preemptive inhaled NO (iNO) would improve allograft function (primary) and reduce complications post-transplantation (secondary). Patients at two university centers (Center A B) were randomized to receive placebo (n = 20/center) or iNO (80 ppm, n the operative phase of transplantation. Data analyzed set intervals for up 9-months compared between groups....
Hypertension secondary to scavenging of NO remains a limitation in the use HBOCs (haemoglobin-based oxygen carriers). Recent studies suggest that nitrite reduction by deoxyhaemoglobin supports signalling. In present study we tested whether would attenuate HBOC-mediated hypertension using HBOC-201 (Biopure), bovine cross-linked, low-oxygen-affinity haemoglobin. similar way unmodified haemoglobin, deoxygenated reduced with rates directly proportional extent deoxygenation. The functional...
Traumatic brain injury (TBI) is the leading cause of injury-related death and disability in patients under age 46 years. Survivors initial often endure systemic complications such as pulmonary infection, Pseudomonas aeruginosa one most common causes nosocomial pneumonia intensive care units. Female are less likely to develop secondary after TBI, pre-clinical studies have revealed a salutary role for estrogen trauma. Therefore, we hypothesized that female mice would experience mortality...
TGF-β1 induces an increase in paracellular permeability and actin stress fiber formation lung microvascular endothelial alveolar epithelial cells via small Rho GTPase. The molecular mechanism involved is not fully understood. Neuronal Wiskott-Aldrich syndrome protein (N-WASP) has essential role structure dynamics. We hypothesized that N-WASP plays a critical these TGF-β1-induced responses. In cell monolayers, we demonstrated down-regulation by short hairpin RNA prevented TGF-β1-mediated...
Bacterial pneumonia and sepsis are both common causes of end-organ dysfunction, especially in immunocompromised critically ill patients. Pre-clinical data demonstrate that bacterial elicit the production cytotoxic tau amyloids from pulmonary endothelial cells, which cause lung brain injury naïve animal subjects, independent primary infection. The contribution infection-elicited to dysfunction has not been examined clinical setting. We hypothesized present bronchoalveolar lavage fluid...
Pseudomonas aeruginosa is a lethal pathogen that causes high mortality and morbidity in immunocompromised critically ill patients. The type III secretion system (T3SS) of P. mediates many the adverse effects infection with this pathogen, including increased lung permeability Toll-like receptor 4/RhoA/PAI-1 (plasminogen activator inhibitor-1)-dependent manner. α-Tocopherol has antiinflammatory properties may make it useful adjunct treatment moribund infection. We measured transendothelial...
Pulmonary edema associated with increased vascular permeability is a severe complication of Pseudomonas (P.) aeruginosa-induced acute lung injury. The mechanisms underlying P are not well understood. In the present study, we investigated role neuronal Wiskott Aldrich syndrome protein (N-WASP) in modulating permeability. Using microvascular endothelial and alveolar epithelial cells, demonstrated that N-WASP downregulation attenuated actin stress fiber formation prevented paracellular...
Acute respiratory distress syndrome (ARDS) is a life-threatening illness characterized by decreased alveolar-capillary barrier function, pulmonary edema consisting of proteinaceous fluid, and inhibition net alveolar fluid transport responsible for resolution edema. There currently no pharmacotherapy that has proven useful to prevent or treat ARDS, two trials using beta-agonist therapy ARDS demonstrated effect. Prior studies indicated IL-8-induced heterologous desensitization the...