A5010058102- Allergic Rhinitis and Sensitization
- Asthma and respiratory diseases
- Contact Dermatitis and Allergies
- Ocular Surface and Contact Lens
- Olfactory and Sensory Function Studies
- Pancreatic function and diabetes
- Ion channel regulation and function
- Food Allergy and Anaphylaxis Research
- Gastroesophageal reflux and treatments
- Ion Transport and Channel Regulation
- Receptor Mechanisms and Signaling
- Diabetes Treatment and Management
- Cellular transport and secretion
- Neuropeptides and Animal Physiology
- Dermatology and Skin Diseases
- Neuroscience of respiration and sleep
- Respiratory and Cough-Related Research
- Urticaria and Related Conditions
- Esophageal and GI Pathology
- Cardiac electrophysiology and arrhythmias
- Nitric Oxide and Endothelin Effects
- Dysphagia Assessment and Management
- Indoor Air Quality and Microbial Exposure
- Social Media in Health Education
- Neurological disorders and treatments
Cliantha (India)
2022-2024
Inflamax Research (Canada)
2014-2023
Allergy and Asthma Medical Group and Research Center
2018
McMaster University
1998-2013
Fields Institute for Research in Mathematical Sciences
2006-2007
University of Toronto
1993-2004
The University of Texas Southwestern Medical Center
2004
University Health Network
2003-2004
Toronto General Hospital
2003
Toronto Western Hospital
1998-2000
In pancreatic β-cells, glucose metabolism signals insulin secretion by altering the cellular array of messenger molecules. ATP is particularly important, given its role in regulating cation channel activity, exocytosis, and events dependent upon hydrolysis. Uncoupling protein (UCP)-2 proposed to catalyze a mitochondrial inner-membrane H+ leak that bypasses synthase, thereby reducing content. Previously, we showed overexpression UCP-2 suppressed glucose-stimulated (GSIS) isolated islets (1)....
Knowledge of how the brain achieves its diverse central control basic physiology is severely limited by virtual absence appropriate cell models. Isolation clonal populations unique peptidergic neurons from hypothalamus will facilitate these studies. Herein we describe mass immortalization mouse primary hypothalamic cells in monolayer culture, resulting generation a vast representation types. Subcloning heterogeneous resulted establishment 38 representative neuronal lines, which 16 have been...
Allergic rhinoconjunctivitis is an increasingly common source of morbidity, with sensitivity to cats accounting for 10% 15% disease burden. Allergy also a major risk factor the development asthma.We sought probe persistence treatment effect novel F el d 1-derived peptide antigen desensitization (Cat-PAD) 1 year after start in subjects cat allergy-induced standardized allergen challenge.In randomized, double-blind, placebo-controlled, parallel-group clinical trial, attended environmental...
Voltage-dependent (Kv) outward K(+) currents repolarize beta-cell action potentials during a glucose stimulus to limit Ca(2+) entry and insulin secretion. Dominant-negative "knockout" of Kv2 family channels enhances glucose-stimulated Here we show that putative Kv2.1 antagonist (C-1) stimulates secretion from MIN6 insulinoma cells in glucose- dose-dependent manner while blocking voltage-dependent currents. C-1-blocked recombinant Kv2.1-mediated more specifically than mediated by Kv1, -3, -4...
Abstract Background This randomized, double‐blind trial was conducted to determine the optimal dose for clinical efficacy of SQ tree SLIT ‐tablet. An environmental exposure chamber ( EEC ) used reduce variability allergen and allow investigation symptom reduction towards different species from birch homologous group in separate sessions. Methods Eligible subjects (N = 219) were randomized receive treatment with placebo or ‐tablet (2, 7, 12 DU 24 weeks. pollen challenges outside season...
Glucagon-like peptide-1 (GLP-1) acts through its G-protein-coupled receptor to enhance glucose-stimulated insulin secretion from pancreatic β-cells. This is believed result modulation of at least two ion channels: ATP-sensitive K+ (KATP) channels and voltage-dependent Ca2+ channels. Here, we report that GLP-1 signaling also regulates the activity β-cell (KV) channels, themselves potent glucose-dependent regulators secretion. activation with exendin 4 (10−8 mol/l) in rat β-cells antagonized...
The role nitric oxide (NO) plays in physiological insulin secretion has been controversial. Here we present evidence that exogenous NO stimulates secretion, and endogenous production occurs is involved the regulation of release. Radioimmunoassay measurement release a dynamic assay exocytosis using dye FM1-43 demonstrated three different donors—hydroxylamine (HA), sodium nitroprusside, 3-morpholinosydnonimine (SIN-1)—each stimulated marked increase from INS-1 cells. Pharmacological...
Allergen exposure chambers (AECs) can be used for controlled to allergenic and non-allergenic airborne particles in an enclosed environment, order (i) characterize the pathological features of respiratory diseases (ii) contribute accelerate clinical development pharmacological treatments allergen immunotherapy allergic disease tract (such as rhinitis, rhinoconjunctivitis, asthma). In guidelines European Medicines Agency products (AIT), role AECs determining primary endpoints dose-finding...
Exocytosis at the apical surface of pancreatic acinar cells occurs in presence physiological concentrations cholecystokinin (CCK) but is inhibited high concentrations. Here we show that Munc18c localized predominantly to basal membranes cells. Supramaximal not submaximal CCK stimulation caused dissociate from plasma membrane, and this displacement was blocked by protein kinase C (PKC) inhibitors. Conversely, whereas analog CCK-OPE alone failed displace agent following minimal PKC activation....
Insulin secretion is initiated by ionic events involving membrane depolarization and Ca(2+) entry, whereas exocytic SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins mediate exocytosis itself. In the present study, we characterize interaction of SNAP-25 (synaptosome-associated 25 kDa) with beta-cell voltage-dependent K(+) channel Kv2.1. Expression Kv2.1, SNAP-25, syntaxin 1A was detected in human islet lysates Western blot, coimmunoprecipitation studies...
GSP301 nasal spray is a fixed-dose combination of the antihistamine olopatadine hydrochloride and corticosteroid mometasone furoate intended for seasonal allergic rhinitis (SAR) treatment.To evaluate efficacy safety once-daily or twice-daily in ragweed pollen environmental exposure chamber.In this randomized, double-blind, double-dummy study, adults (18-65 years old) with SAR were equally randomized to 665 μg 25 (twice-daily GSP301), 50 (once-daily US Food Drug Administration-approved...
Studies indicate that allergy sufferers remain dissatisfied with available antiallergic therapies. A new convenient formulation of solubilized steroid combined in the same nasal spray solution antihistamine may provide added symptom relief. The objective was to evaluate effects CDX-947 (solubilized budesonide) and CDX-313 azelastine + against their suspension-type comparators (budesonide [Rhinocort Aqua {RA}] or budesonide [Astelin] {AS} RA]) placebo on symptoms patients exposed controlled...
Delayed-rectifier K<sup>+</sup> channels (K<sub>DR</sub>) are important regulators of membrane excitability in neurons and neuroendocrine cells. Opening these voltage-dependent results repolarization, leading to the closure Ca<sup>2+</sup>channels cessation insulin secretion islet β Using patch clamp techniques, we have demonstrated that activity K<sub>DR</sub> channel subtype, K<sub>V</sub>1.1, identified by its specific blocker dendrodotoxin-K, is inhibited SNAP-25 insulinoma HIT-T15 A...
In pancreatic β‐cells, voltage‐dependent K + (Kv) channels repolarise glucose‐stimulated action potentials. Kv are therefore negative regulators of Ca 2+ entry and insulin secretion. We have recently demonstrated that Kv2.1 mediates the majority β‐cell outward current now investigate function native at near‐physiological temperatures (32‐35 °C). While currents inactivated little room temperature, both fast‐inactivation (111.5 ± 14.3 ms) slow‐inactivation (1.21 0.12 s) was observed 32‐35 °C....
To assess the prophylactic and treatment activity of reproxalap, a novel reactive aldehyde species inhibitor, in real-world model allergen exposure.In randomized, double-masked, vehicle-controlled, crossover Phase 2 trial, 70 adult patients with ≥2 years moderate to severe allergic conjunctivitis history, positive skin test ragweed pollen, chamber-induced ocular itching redness scores ≥2.5 (both scales range from 0 4), respectively, were randomized 1:1:1 one three sequences: 0.25% 0.5%...
Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone with powerful antidiabetogenic effects that are thought to be mediated by adenylyl cyclase (AC). Recently, we generated two GLP-1 receptor mutant isoforms (IC3-1 and DM-1) displayed efficient ligand binding the ability promote Ca2+ mobilization from intracellular stores but lacked couple AC. In present study, wild-type rat (WT-GLP-1 R) or IC3-1 DM-1 forms were expressed for first time in insulin-producing HIT-T15 cells. Only cells...
GSP301 is a fixed-dose combination (FDC) of the antihistamine olopatadine hydrochloride and corticosteroid mometasone furoate developed as single nasal spray (NS).To assess relative bioavailability administered FDC versus two monotherapy NS formulations.In this single-dose, open-label, crossover study, healthy adults (age range, 18-65 years) were randomized equally to one six treatment sequences for three 72-hour periods with (olopatadine 665 μg-mometasone 50 μg), component (MF-sponsor, U.S....
Objectives: Many allergic conjunctivitis (AC) patients are inadequately treated with conventional therapies or require steroids. EBI-005 was developed to address the late phase response. This study's objectives were evaluate two adapted clinical models for this indication and assess safety biological activity of in AC. Methods: In randomized, double-masked, vehicle-controlled study, 159 subjects moderate-to-severe AC randomized topical (5 mg/mL) vehicle control given 3 times per day...