A5029964640- Hemoglobinopathies and Related Disorders
- Heme Oxygenase-1 and Carbon Monoxide
- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Erythrocyte Function and Pathophysiology
- Ion channel regulation and function
- Neuropeptides and Animal Physiology
- Hemoglobin structure and function
- Memory and Neural Mechanisms
- Iron Metabolism and Disorders
- Musculoskeletal pain and rehabilitation
- Nicotinic Acetylcholine Receptors Study
- Bone and Joint Diseases
- Cholinesterase and Neurodegenerative Diseases
- Receptor Mechanisms and Signaling
- Blood groups and transfusion
- Pharmacological Effects and Toxicity Studies
- Neonatal Health and Biochemistry
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Stroke Rehabilitation and Recovery
- Acute Myeloid Leukemia Research
- Genomics, phytochemicals, and oxidative stress
- Myofascial pain diagnosis and treatment
- Nutrition and Health in Aging
- Body Composition Measurement Techniques
University of Minnesota
2014-2024
Philadelphia University
2023-2024
Imam Abdulrahman Bin Faisal University
2012-2022
University of Minnesota Medical Center
2010-2021
Arabian Gulf University
2017
New York Institute of Technology
2011
New York Institute of Technology
2007-2010
Hashemite University
2003-2006
University of Alberta
1994-2002
Tennessee State University
1998-2001
Aims: Heme derived from hemolysis is pro-oxidative and proinflammatory promotes vaso-occlusion in murine models of sickle cell disease (SCD), suggesting that enhanced detoxification heme may be beneficial. Nuclear factor erythroid-2-related factor-2 (Nrf2) transcription pathway the principal cellular defense system responding to stress. Dimethyl fumarate (DMF), a drug approved for treatment multiple sclerosis, provides neuroprotection by activating Nrf2-responsive genes. We hypothesized...
During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation thrombosis. Plasma haptoglobin hemopexin scavenge free heme, respectively, but can be depleted in hemolytic states. Haptoglobin supplementation protect tissues, including the vasculature, liver kidneys. It is widely assumed that these protective effects are due primarily to clearance vasculature. However, this simple assumption does not account for consequent cytoprotective adaptation...
Sciatic nerve section (axotomy) increases the excitability of rat dorsal root ganglion (DRG) neurons. The changes in Ca2+ currents, K+ sensitive current, and hyperpolarization-activated cation current (I(H)) that may be associated with this effect were examined by whole cell recording. Axotomy affected same conductances all types DRG neuron. In general, largest seen "small" cells smallest "large" cells. High-voltage-activated channel (HVA-I(Ba)) was reduced axotomy. Although currents...
The spontaneous, ectopic activity in sensory nerves that is induced by peripheral nerve injury thought to contribute the generation of “neuropathic” pain humans. To examine cellular mechanisms underlie this activity, neurons rat L 4 –L 5 dorsal root ganglion (DRG) were first grouped as “large,” “medium,” or “small” on basis their size (input capacitance) and action potential (AP) shape. A fourth group cells exhibited a pronounced afterdepolarization (ADP) defined AD-cells. Whole cell...
The antidiarrheal effects of the aqueous extract Punica granatum. L. (Punicaceae) peels were evaluated in rats. Studies carried out on isolated rat ileum, gastrointestinal motility vivo., and castor oil–induced diarrhea results revealed that exhibited a concentration-dependent inhibition spontaneous movement ileum attenuated acetylcholine-induced contractions. (100, 200, 300, 400 mg/kg) also caused dose-dependent decrease transit markedly protected rats against enteropooling. intraperitoneal...
Summary Endothelial activation and sickle red blood cell (RBC) adhesion are central to the pathogenesis of disease (SCD). Quantitatively, RBC‐derived extracellular vesicles (REVs) more abundant from SS RBCs compared with healthy (AA RBCs). Sickle REVs (SS REVs) known promote endothelial (EC) through signalling transcriptional regulation at longer terms. However, REV‐mediated short‐term non‐transcriptional response EC is unclear. Here, we examined impact on acute microvascular RBC 2 h....
Dorsal root ganglion (DRG) neurons from control rats or in which the sciatic nerve had been sectioned were studied by whole-cell recording techniques. Noradrenaline (10-100 micro;M) activated beta-adrenoceptors and increased L-type Ca2+ channel current DRG cells, but this little effect on excitability (the number of action potentials generated a pulse at rheobasic strength). By contrast, cells nerve-damaged animals, noradrenaline alpha2-adrenoceptors, suppressed N-type current, excitability....
Carbon monoxide (CO) at low, non-toxic concentrations has been previously demonstrated to exert anti-inflammatory protection in murine models of sickle cell disease (SCD). However CO delivery by inhalation, CO-hemoglobin infusion or CO-releasing molecules presents problems for daily administration. Oral administration a CO-saturated liquid avoids many these issues and potentially provides platform self-administration SCD patients. To test if orally-delivered could modulate vaso-occlusion...
Innate immune complement activation may contribute to sickle cell disease (SCD) pathogenesis. Ischemia‐reperfusion physiology is a key component of the inflammatory and vaso‐occlusive milieu in SCD associated with activation. C5a an anaphylatoxin, potent pro‐inflammatory mediator that can activate leukocytes, platelets, endothelial cells, all which play role vaso‐occlusion. We hypothesize hypoxia‐reoxygenation (H/R) mice activates complement, promoting inflammation At baseline after H/R,...
The most common treatment for patients with sickle cell disease (SCD) is the chemotherapeutic hydroxyurea, a therapy pleiotropic effects, including increasing fetal hemoglobin (HbF) in red blood cells and reducing adhesion of white to vascular endothelium. Hydroxyurea has been proposed mediate these effects through mechanism cellular cGMP levels. An alternative path levels use phosphodiesterase-9 inhibitors that selectively inhibit hydrolysis increase We have developed novel, potent...
People living with sickle cell disease (SCD) face intermittent acute pain episodes due to vaso-occlusion primarily treated palliatively opioids. Hemolysis of erythrocytes promotes release heme, which activates inflammatory adhesion proteins on endothelial cells and circulating cells, promoting vaso-occlusion. In this study, plasma-derived hemopexin inhibited heme-mediated cellular externalization P-selectin von Willebrand factor, expression IL-8, VCAM-1, heme oxygenase-1 in cultured a...
Context: The leaf of sage Salvia officinalis L. (Lamiaceae) is reputed in the folk medicine Arabia, and Jordan particular, to relieve pain associated with gastrointestinal disturbance.Objectives: Evaluation antinociceptive anti-inflammatory activities aqueous butanol extracts S. leaf.Materials methods: analgesic effects extract (10, 31.6, 100, 316, 1000 mg/kg) 316 were studied using hot-plate test for mice formalin-induced paw licking rats. compared those morphine influence naloxone on these...
Sickle cell disease (SCD) patients have low serum hemopexin (Hpx) levels due to chronic hemolysis. We hypothesized that in SCD mice, hepatic overexpression of would scavenge the proximal mediator vascular activation, heme, and inhibit inflammation microvascular stasis. To examine protective role Hpx SCD, we transplanted bone marrow from NY1DD mice into Hpx−/− or Hpx+/+ C57BL/6 mice. Dorsal skin fold chambers were implanted 13 wks post-transplant, stasis (% nonflowing venules) was evaluated...
There is some doubt as to the effectiveness of opioids in management neuropathic pain. We therefore examined actions morphine and opioid-like peptide nociceptin (both 1 μ) on dorsal root ganglion (DRG) neurons that were isolated from control or nerve-injured rats. Both substances reduced ω-conotoxin (CTX) GVIA-sensitive, N-type Ca 2+ channel current small persistent nifedipine/ CTX-insensitive (non-N, non-L type) current. Nifedipine-sensitive L-type was unaffected. The effect antagonized by...
Section of rat sciatic nerve (axotomy) increases the excitability neurons in L(4)-L(5) dorsal root ganglia (DRG). These changes are more pronounced animals that exhibit a self-mutilatory behavior known as autotomy. We used whole cell recording to examine tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) components sodium channel currents (I(Na)) may contribute axotomy-induced excitability. Cells were initially divided on basis size into "large," "medium," "small" groups....
In sickle cell disease (SCD), heme released during intravascular hemolysis promotes oxidative stress, inflammation, and vaso-occlusion. Conversely, free can also activate expression of antioxidant globin genes. Heme binds to the transcription factor BACH1, which represses NRF2-mediated gene transcription. ASP8731, is a selective small molecule inhibitor BACH1. We investigated ability ASP8731 modulate pathways involved in SCD pathophysiology. HepG2 liver cells, increased HMOX1 FTH1 mRNA....
Vaso-occlusive pain episodes (VOE) cause severe in patients with sickle cell disease (SCD). events promote ischemia/reperfusion pathobiology that activates complement. We hypothesized complement activation is linked to VOE. used cold induce VOE the Townes homozygous for hemoglobin S (HbSS) mouse model and inhibitors determine whether anaphylatoxin C5a mediates a dorsal skinfold chamber measure microvascular stasis (vaso-occlusion) von Frey filaments applied plantar surface of hind paw assess...