- Connexins and lens biology
- Ion Channels and Receptors
- Ion channel regulation and function
- Glaucoma and retinal disorders
- Neuroscience and Neuropharmacology Research
- Nitric Oxide and Endothelin Effects
- Retinal Development and Disorders
- Ocular Surface and Contact Lens
- Ion Transport and Channel Regulation
- Cardiac electrophysiology and arrhythmias
- Biochemical effects in animals
- Intraocular Surgery and Lenses
- Drug Transport and Resistance Mechanisms
- Aldose Reductase and Taurine
- Tissue Engineering and Regenerative Medicine
- Photoreceptor and optogenetics research
- Advanced Glycation End Products research
- Neonatal Health and Biochemistry
- Nicotinic Acetylcholine Receptors Study
- Reproductive tract infections research
- Neuroscience and Neural Engineering
- Neurobiology and Insect Physiology Research
- Receptor Mechanisms and Signaling
- Cholinesterase and Neurodegenerative Diseases
- Plant and Biological Electrophysiology Studies
University of Arizona
2016-2025
Bangabandhu Sheikh Mujib Medical University
1970-2021
Yahoo (United Kingdom)
2018
Banner - University Medical Center Tucson
2018
Yale University
2009-2015
Dalhousie University
2015
Thomas Jefferson University
2003-2014
Louisiana State University Health Sciences Center New Orleans
2013
University of Pennsylvania
2005-2010
University of Louisville
2006
Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey countries on 6 continents define (MTA), disparities in MTA, and its determinants global scale.Our was 75 through Mission Thrombectomy 2020+ network between November 22, 2020, February 28, 2021. The primary end points were current annual operator availability, center availability. MTA defined as...
Aqueous humour (AH) is an important intraocular fluid responsible for the supply of nutrients to and removal metabolic wastes from avascular tissues eye. It also indispensable maintenance optical properties The dynamics AH are frequently associated with potentially blinding disease called glaucoma. Pharmacological treatment glaucoma generally aims lower pressure by reducing formation. However, mechanism underlying formation still not well understood. Understanding its regulation paramount...
In several tissues, transient receptor potential vanilloid 4 (TRPV4) channels are involved in the response to hyposmotic challenge. Here we report TRPV4 protein porcine lens epithelium and show that activation is an important step of stress. Hyposmotic solution (200 mosM) elicited ATP release from intact lenses antagonists HC 067047 RN 1734 prevented release. isosmotic solution, agonist GSK1016790A (GSK) When propidium iodide (PI) (MW 668) was present bathing medium, GSK both increased PI...
The organic anion transporters 1 and 3 (OAT1 OAT3) cation transporter 2 (OCT2) are important for renal tubular drug secretion. In contrast, evidence OAT2 expression in the human kidney is limited, its role transport unknown. Both mRNA (real-time polymerase chain reaction) protein (Western blotting) were detected cortex from eight donors, interindividual variability levels was 3-fold. localized (by immunohistochemistry) to basolateral domain of tubules, as OAT1 OAT3. absolute abundance...
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads invariably to fatal paralysis associated with motor neuron degeneration and muscular atrophy. One gene ALS encodes the DNA/RNA-binding protein Fused in Sarcoma (FUS). There now exist two Drosophila models of ALS. In one, human FUS ALS-causing mutations expressed fly neurons; other, cabeza (caz), homolog FUS, ablated. These FUS-ALS flies exhibit larval locomotor defects indicative neuromuscular...
Kv4 channels represent the main class of brain A-type K+ that operate in subthreshold range membrane potentials (Serodio, P., E. Vega-Saenz de Miera, and B. Rudy. 1996. J. Neurophysiol. 75:2174– 2179), their function depends critically on inactivation gating. A previous study suggested cytoplasmic NH2- COOH-terminal domains Kv4.1 act concert to determine fast phase complex time course macroscopic (Jerng, H.H., M. Covarrubias. 1997. Biophys. 72:163–174). To investigate structural basis slow...
This study evaluated poly(ADP-ribose) polymerase (PARP) inhibition as a new therapeutic approach for peripheral diabetic neuropathy using clinically relevant animal model and endpoints, nitrotyrosine (NT), TNF-α, nitrite/nitrate potential biomarkers of the disease. Control streptozotocin-diabetic rats were maintained with or without treatment orally active PARP inhibitor 10-(4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]anthracen-3-one (GPI-15,427), 30 mg kg−1 d−1, 10 wk after...
<h3>Objective</h3> Barrett9s oesophagus is a premalignant disease associated with oesophageal adenocarcinoma. The major goal of this study was to determine the mechanism responsible for bile acid-induced alteration in intracellular pH (pH<sub>i</sub>) and its effect on DNA damage cells derived from normal (HET1A) or (CP-A). <h3>Design</h3> Cells were exposed acid cocktail (BA) and/or presence/absence inhibitors nitric oxide synthase (NOS) sodium–hydrogen exchanger (NHE). Nitric (NO),...
Purinergic receptors in lens epithelium suggest function can be altered by chemical signals from aqueous humor or the itself. Here we show release of ATP intact porcine lenses exposed to hyposmotic solution (200 mOsm). 18α-glycyrrhetinic acid (AGA) added together with probenecid eliminated increase. N-ethylmaleimide µM), an exocytotic inhibitor, had no significant effect on Lenses displayed a ~400% increase propidium iodide (PI) entry into epithelium. The increased ability PI (MW 668) enter...
Bicarbonate transport plays a role in aqueous humor (AH) secretion. The authors examined bicarbonate mechanisms and carbonic anhydrase (CA) porcine nonpigmented ciliary epithelium (NPE).Cytoplasmic pH (pH(i)) was measured cultured NPE loaded with BCECF. Anion exchanger (AE), sodium cotransporter (NBC), CA were by RT-PCR immunolocalization. AH secretion the intact eye using fluorescein dilution technique.Anion AE2, CAII, CAIV abundant layer. In superfused CO(2)/HCO(3)(-)-free HEPES buffer,...
Purpose.: Elevated intraocular pressure is associated with glaucomatous optic nerve damage. Other investigators have shown functional changes in head astrocytes subjected to elevated hydrostatic (HP) for 1 5 days. Recently, the authors reported ERK1/2, p90RSK and NHE1 phosphorylation after 2 hours. Here they examine calcium responses at onset of HP determine what precedes ERK1/2 phosphorylation. Methods.: Cytoplasmic concentration ([Ca2+]i) was measured cultured rat loaded fura-2. The cells...
Many aspects of behavior and physiology are under circadian control. In Drosophila, the molecular clock that regulates rhythmic patterns has been extensively characterized. contrast, genetic loci involved in linking to alterations motor activity have remained elusive. a forward-genetic screen, we uncovered new component output pathway, which termed dyschronic (dysc). dysc mutants exhibit arrhythmic locomotor behavior, yet their eclosion rhythms normal protein cycling remains intact....
Purpose: The lens uses feedback to maintain zero pressure in its surface cells. Positive pressures are detected by transient receptor potential vanilloid (TRPV4), which initiates a cascade that reduces cell osmolarity. first step is opening of gap junction hemichannels. One purpose the current study was identify connexin(s) Negative TRPV1, increases increase osmolarity initially reported be through inhibition Na/K ATPase activity, but recent it stimulation Na/K/2Cl (NKCC) cotransport. A...
The porcine lens response to a hyperosmotic stimulus involves an increase in the activity of ion cotransporter sodium-potassium/two-chloride 1 (NKCC1). Recent studies with agonists and antagonists pointed mechanism that appears depend on activation transient receptor potential vanilloid (TRPV1) channels. Here, we compare responses lenses cultured epithelium obtained from TRPV1 −/− wild type (WT) mice. Hydrostatic pressure (HP) surface cells was determined using manometer-coupled...
Cerebellar granule neurons possess a non-inactivating K+ current, which controls resting membrane potentials and modulates the firing rate by means of muscarinic agonists. kcr1 was cloned from cerebellar cDNA library suppression cloning. KCR1 is novel protein with 12 putative transmembrane domains enhances functional expression current in Xenopus oocytes. also accelerates activation rat EAG channels expressed oocytes or COS-7 cells. Far-Western blotting revealed that proteins interacted each...
1. We developed a novel method to isolate nonpigmented epithelial (NPE) cells from porcine eyes in order examine Na,K-ATPase responses nitric oxide (NO) donors specifically the epithelium. 2. Cells were treated with NO and other test compounds for 20 min prior activity measurement. 3. donors, sodium nitroprusside (SNP, 1 microM-1 mM), azide (100 nM-1 microM) S-nitroso-N-acetylpenicillamine (1 mM) caused significant concentration-dependent inhibition of activity. Detection nitrite medium...
Lens ion homeostasis is crucial in maintaining water content and, turn, refractive index and transparency of the multicellular syncytium-like structure. New information emerging on regulation transport lens by mechanisms that rely transient receptor potential vanilloid (TRPV) channels. We found recently TRPV1 activation leads to Ca2+/PKC-dependent ERK1/2 signaling. Here, we show agonist capsaicin (100 nM) hyperosmotic solution (350 vs. 300 mosM) each caused an increase bumetanide-inhibitable...
PURPOSE. To examine extracellular ATP for its ability to mobilise intracellular calcium in bovine ciliary epithelial cells; establish and characterise P2Y 2 receptor-mediated signal transduction this tissue. METHODS. Bovine cells were isolated cultured until confluence. The reseeded on sterile coverslips grown obtain monolayers, then loaded with fura-2. Fluorescence was measured by a computer-controlled spectrofluorimeter values calculated concentration. ATP, analogues other drugs tested...
To investigate the role of active chloride secretion by ciliary epithelium in formation aqueous humor (AH), using vitro perfused eye.Bovine eyes collected from an abattoir were cannulated through ophthalmic artery and with oxygenated Krebs' solution at 37 degrees C. Aqueous (AHF) was measured fluorescein-dilution technique. Drugs added to perfusate and/or anterior chamber.NaK-adenosine triphosphatase (ATPase) inhibitor, ouabain (1.0 mM), produced a significant reduction AHF 46% 42% when...
The effect of nitric oxide (NO) on aqueous humour formation (AHF) and intraocular pressure (IOP) was studied using NO donors, sodium azide (AZ) nitroprusside (SNP). Using the porcine arterially perfused eye preparation, drug effects AHF IOP were measured by fluorescein dilution manometry, respectively. Perfusion ocular vasculature also monitored digital transducer pen recorder. L ‐Arginine (1.0 m M ), a precursor NO, but not D ‐arginine inactive analogue, produced significant reduction in...
KCNQ2 and KCNQ3 ion channel pore-forming subunits coassemble to form a heteromeric voltage-gated potassium that underlies the neuronal M-current. We others showed calmodulin (CaM) binds specific sequence motifs in C-terminal domain of KCNQ3. also found fusion protein containing CaM-binding motif, coexpressed with KCNQ3, competes full-length for CaM binding thereby decreases KCNQ2/3 current density heterologous cells. have explored importance generation native M-current regulation membrane...
The nonpigmented epithelium (NPE) of the ciliary body represents an important component blood-aqueous barrier eye. Many therapeutic drugs penetrate poorly across NPE into aqueous humor eye interior. Several these drugs, such as methotrexate, vincristine, and etoposide, are substrates multidrug resistance-associated protein 2 (MRP2). Abundant MRP2 was detected by Western blot in homogenates human freshly dissected porcine NPE. In cultured NPE, intracellular accumulation calcein (1.8-fold),...