A5036121921- Pesticide Exposure and Toxicity
- Ion channel regulation and function
- Carcinogens and Genotoxicity Assessment
- Smoking Behavior and Cessation
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Cell death mechanisms and regulation
- Ion Channels and Receptors
- Cardiac electrophysiology and arrhythmias
- Air Quality and Health Impacts
- Indoor Air Quality and Microbial Exposure
- Inhalation and Respiratory Drug Delivery
- Sulfur Compounds in Biology
- Pancreatic function and diabetes
- Botulinum Toxin and Related Neurological Disorders
- Effects and risks of endocrine disrupting chemicals
- Drug-Induced Hepatotoxicity and Protection
- Retinoids in leukemia and cellular processes
- Consumer Attitudes and Food Labeling
- Bacillus and Francisella bacterial research
- Coffee research and impacts
- Hereditary Neurological Disorders
- Genomics, phytochemicals, and oxidative stress
- Salivary Gland Disorders and Functions
- Asthma and respiratory diseases
Research Applications (United States)
2017-2025
United States Army
2009-2017
United States Department of the Army
2007-2014
DEVCOM Army Research Laboratory
2010
Tulane University
2005-2008
Mibefradil is a Ca<sup>2+</sup> channel antagonist that inhibits both T-type and high-voltage-activated channels. We previously showed block of channels by mibefradil occurs through the production an active metabolite intracellular hydrolysis. In present study, we modified structure to develop nonhydrolyzable analog, (1<i>S</i>, 2<i>S</i>)-2-(2-(<i>N</i>-[(3-benzimidazol-2-yl)propyl]-<i>N</i>-methylamino)ethyl)-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphtyl cyclopropanecarboxylate...
Introduction Oral nicotine pouches (ONPs) are a newer category of smokeless tobacco products containing pharmaceutical-grade but no leaf. These have the potential to help smokers transition away from cigarettes. To assess their role as alternatives cigarettes, we evaluated abuse liability (AL) Velo ONPs with varying content (4–12 mg per pouch), pouch size (600 or 400 mg) and flavor (six varieties) in comparison high (cigarettes) low (nicotine replacement therapy [NRT] gum) AL comparators....
Abstract Background Immortalized neuronal cell lines can be induced to differentiate into more mature neurons by adding specific compounds or growth factors the culture medium. This property makes attractive as in vitro models study functions and neurotoxicity. The clonal human neuroblastoma BE(2)-M17 line is known a prominent type treatment with trans-retinoic acid. However, there lack of information on morphological functional aspects these differentiated cells. Results We studied effects...
NNC 55-0396 is a structural analog of mibefradil (Ro 40-5967) that inhibits both T-type and high-voltage-activated (HVA) Ca2+ channels with higher selectivity for channels. The inhibitory effect on HVA can be attributed to hydrolyzed metabolite the drug: methoxy acetate side chain removed by intracellular enzymes, thus it forms (1S,2S)-2-(2-(N-[(3-benzoimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphtyl hydroxy dihydrochloride (dm-mibefradil), which...
We have shown that sulfur mustard (SM; bis-(2-chloroethyl) sulfide), an alkylating, vesicating chemical warfare agent, causes dermal toxicity, including skin microblisters, via the induction of both death receptor (DR) and mitochondrial pathways apoptosis in human epidermal keratinocytes. While SM is known for its skin-vesicating properties, respiratory tract lesions are main source morbidity mortality after inhalation exposure. We, therefore, investigated whether induces apoptotic cell...
The VITROCELL VC1® smoke exposure machine is an aerosol system that has been used to conduct toxicological assessments with cigarettes and e-cigarettes can be the human 3D EpiAirway™ tissue model (MatTek Corporation). goals of this study were assess parameters VC1, evaluate donor-to-donor variability three EpiAirway donors following endpoints: viability, barrier integrity, gene promoter/expression regulation. Additionally, we applied effects from two reference combustible e-cigarettes. Whole...
High-voltage-activated (HVA) calcium channels are known to be the primary source of for glucose-stimulated insulin secretion. However, few studies have investigated how these can regulated by chronically elevated levels glucose. In present study, we determined level expression four major HVA (N-type, P/Q-type, L(C)-type, and L(D)-type) in rat pancreatic beta-cells. Using quantitative real-time PCR (QRT-PCR), found all genes insulinoma cells (INS-1) isolated islet cells. We then role each...
Sulfur mustard (SM) is a vesicant chemical warfare and terrorism agent. Besides skin eye injury, respiratory damage has been mainly responsible for morbidity mortality after SM exposure. Previously, it was shown that suppressing the death receptor (DR) response by dominant-negative Fas-associated domain protein prior to exposure blocked apoptosis microvesication in skin. Here, we studied whether antagonizing Fas (FasR) pathway small-interfering RNA (siRNA) applied would prevent and, thus,...
Assessment of in vitro cytotoxicity is an important component tobacco product toxicological evaluations. However, current methods regulatory testing involve exposing monolayer cell cultures to various preparations aerosols from cigarettes or other emerging products such as electronic nicotine delivery systems (ENDS), which are not representative human exposure. In the present study, a whole aerosol (WA) system was used expose lung epithelial (2D and 3D) determine potential six Vuse Alto ENDS...
Heated tobacco products (HTPs) are non-combustible, inhaled that generate an aerosol with fewer and lower levels of toxicants, a potential to reduce risk relative cigarette smoking. Here, we assessed in vitro toxicological effects three menthol (glo neo neoCLICK, Smooth Menthol Fresh Menthol) one non-menthol (neo Tobacco) variants glo HTP, along market comparators for cigarettes HTPs. Limited chemical characterization the study revealed significantly acetaldehyde, acrolein, crotanaldehyde...
Chronic exposure of pancreatic beta-cells to high concentrations glucose impairs the insulin secretory response further stimulation. This phenomenon is referred as desensitization. It has been shown that desensitization associated with abnormal elevation beta-cell basal intracellular free Ca2+ concentration ([Ca2+]i). We have investigated relationship between and L-type (Cav1.3) channel translocation in insulin-secreting cells. Glucose stimulation or membrane depolarization induced a...
The Vitrocell® VC10® smoke exposure system offers multiple platforms for air liquid interface (ALI) and agar (AAI) that mimic in vivo conditions assessing toxicological impact of whole using vitro assays. aim this study was to investigate compare dosimetry techniques may be employed during combustible cigarette the smoking robot. following were assessed: (1) quartz crystal microbalances (QCMs), (2) aerosol photometers (using area under curve, AUC), (3) fluorescence anhydrous dimethyl...
The rapid development associated with Next Generation Tobacco Products (NGTP) has necessitated the of high throughput methodologies to test their genotoxic potential in vitro when compared conventional cigarette smoke (CS). An assessment two Vitrocell® Mammalian 6/48 exposure modules three independent experiments was made by comparing results from multiple dosimetric techniques applied aerosol generated 3R4F Kentucky Reference cigarettes, commercially available electronically heated tobacco...
Oral disease is frequently associated with viral and environmental exposures oral hygiene. The use of tobacco a risk factor in the development disease. Cytotoxicity, inflammatory response, oxidative stress have been reported to role These three endpoints were evaluated 3D human buccal model, EpiOral™, following exposure CORESTA reference smokeless products (CRPs) cigarette whole smoke. CRPs for Swedish style snus (CRP1), moist snuff (CRP2), dry (CRP3) each extracted complete artificial...
The assessment of potential cytotoxicity or genotoxicity combustible tobacco products has historically been performed using partitioned exposures (i.e. total particulate matter [TPM], gas vapor phase [GVP]) rather than whole smoke. VITROCELL® VC10® smoke exposure system offers multiple platforms for air liquid interface (ALI) agar (AAI) to mimic in vivo-like conditions assessing the toxicological impact vitro assays (e.g. cytotoxicity, mutagenicity and DNA modifications). aims this study...
The US military has placed major emphasis on developing therapeutics against nerve agents (NA). Current efforts are hindered by the lack of effective in vitro cellular models to aid preliminary screening potential candidate drugs/antidotes. development an model discovering new NA would be highly beneficial. In this regard, we have examined response a differentiated hybrid neuronal cell line, NSC-34, VX. VX-induced apoptosis NSC-34 cells was measured monitoring changes caspase-3 and caspase-9...