Respiratory Tract Diseases Commons^™

A Quantitative Analysis Of The Efficacy Of Various Essential Oils Against The Sars Cov-2 Virus, Elizabeth Wagstaff, Chandrelyn Kraczek, Jack Brandon Lopez

Annual Research Symposium

A poster presentation and abstract for the Roseman Symposium. The project focuses on testing 3 essential oil blends and two disinfectants containing an essential oil blend against SARS CoV-2 in response to the COVID-19 pandemic. The project procedure involves plaque assays, disinfection, and neutralization techniques.

Optimizing Antidotal Treatment With The Oral Hsp90 Inhibitor Tas-116 Against Hydrochloric Acid-Induced Pulmonary Fibrosis In Mice, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropolou, Tierney Day, John Catravas

Bioelectrics Publications

Exposure to high concentrations of hydrochloric acid (HCl) can lead to severe acute and chronic lung injury. In the aftermath of accidental spills, victims may be treated for the acute symptoms, but the chronic injury is often overlooked. We have developed a mouse model of acute and chronic lung injury, in which the peak of acute lung injury occurs on the day 4 after HCl exposure. We have also demonstrated that HSP90 inhibitors are effective antidotes when administered starting 24 h after HCl. In this study we examined the hypothesis that the novel oral HSP90 inhibitor TAS-116 can effectively ameliorate …

Therapeutic Approaches For Respiratory Distress Syndrome, Franck J. Kamga Gninzeko

Theses and Dissertations

Respiratory distress syndrome (RDS) is characterized by shortness of breath and low oxygen levels. RDS affects the neonatal and adult populations. In the neonatal population, RDS can be classified as NRDS (Neonatal respiratory distress syndrome), while in adults, it is known as ARDS (acute respiratory distress syndrome). This dissertation examines a therapeutic approach to NRDS and a mechanistic approach to ARDS with in vivo and in vitro models of lung injury. NRDS is characterized by a deficiency or lack of surfactant. Surfactant is an essential compound composed of phospholipids and proteins to prevent the lungs from collapsing. There are several …

Engineering And Characterization Of Human Β-Defensin-3 And Its Analogues And Microcin J25 Peptides Against Mannheimia Haemolytica And Bovine Neutrophils, Harpreet Dhingra, Kamaljit Kaur, Baljit Singh

Pharmacy Faculty Articles and Research

Mannheimia haemolytica-induced bovine respiratory disease causes loss of millions of dollars to Canadian cattle industry. Current antimicrobials are proving to be ineffective and leave residues in meat. Antimicrobial peptides (AMPs) may be effective against M. haemolytica while minimizing the risk of drug residues. Cationic AMPs can kill bacteria through interactions with the anionic bacterial membrane. Human β-Defensin 3 (HBD3) and microcin J25 (MccJ25) are AMPs with potent activity against many Gram-negative bacteria. We tested the microbicidal activity of wild-type HBD3, three HBD3 peptide analogues (28 amino acid, 20AA, and 10AA) derived from the sequence of natural HBD3, and MccJ25 …

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

Graduate Theses/Dissertations

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …

Analysis Of Covid-19 Prevention And Treatment In Taiwan (Review), Yu-Jen Chiu, Jo‑Hua Chiang, Chih-Wei Fu, Mann-Jen Hour, Hai-Anh Ha, Sheng-Chu Kuo, Jen-Jyh Lin, Ching-Chang Cheng, Shih‑Chang Tsai, Yu‑Shiang Lo, Yu‑Ning Juan, Yih-Dih Cheng, Jai-Sing Yang, Fuu‑Jen Tsai

BioMedicine

Coronavirus disease 2019 (COVID‐19) has been spreading worldwide with a mind-boggling speed. According to a statement from World Health Organization (WHO), COVID-19 has infected more than six billions people and caused more than one and half million passing in the world. Based on previous experience with SARS, the Taiwanese government had decided to block viral transmission during its early stages. This review sums up the clinical characteristics, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) viral infection process, diagnostic methods, preventive strategy, and the executive proportions of COVID-19, as well as the name-based mask distribution system (NBMDS) in Taiwan. We …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Retrospective Review Of Anticoagulation Regimens Used For The Prevention Of Venous Thromboembolisms In Critically Ill Patients Infected With Sars-Cov-2, Tony Nguyen, Heidi Clarke

All Publications

No abstract provided.

Impact Of A Pharmacist-Driven Methicillin-Resistant Staphylococcus Aureus Nasal Swab Protocol On The De-Escalation Of Empiric Vancomycin In The Setting Of Community Acquired Pneumonia, Grether Hernandez Gama, Winifred Pardo, Wilbert Fuerte, James Adefisoye

All Publications

No abstract provided.

The Effect Of Hydroxychloroquine On In-Hospital Mortality In Covid-19, Samar Aboulenain, Nakeya Dewaswala, Fergie Ramos, Pedro Torres, Ahmed Abdallah, Mohamed Abdul Qader, Baher Al-Abbasi, Charles R. Bornmann, Karolina N. Dziadkowiec, Kai Chen, Jesus E. Pino, Robert Chait, Kleper De Almeida

HCA Healthcare Journal of Medicine

Background: Hydroxychloroquine (HCQ) is an antimalarial medication that has been tested against various viral illnesses. The available evidence regarding the role of HCQ in the coronavirus disease 2019 (COVID-19) remains controversial.

Methods: This is a comparative retrospective cohort study that aims to evaluate the efficacy and safety of HCQ in hospitalized patients with COVID-19. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included ICU admission rate, mechanical ventilation, prolonged length of stay (LOS), QTc prolongation and cardiac arrest.

Results: A cohort of 175 hospitalized patients with COVID-19 were included with a median (interquartile range [IQR]) age of 66 [48–79] …

Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi

Pharmacy Faculty Articles and Research

COVID-19 caused by the SARS-CoV-2 virus is a fast emerging disease with deadly consequences. The pulmonary system and lungs in particular are most prone to damage caused by the SARS-CoV-2 infection, which leaves a destructive footprint in the lung tissue, making it incapable of conducting its respiratory functions and resulting in severe acute respiratory disease and loss of life. There were no drug treatments or vaccines approved for SARS-CoV-2 at the onset of pandemic, necessitating an urgent need to develop effective therapeutics. To this end, the innate RNA interference (RNAi) mechanism can be employed to develop front line therapies against …

Exogenous Lipoid Pneumonia Complicated By Mineral Oil Asperation In A Patient With Chronic Constipation: A Case Report And Review, Hafiz Muhammad Jeelani, Muhammad Mubbashir Sheikh, Belaal Sheikh, Hafiz Mahboob, Anchit Bharat

School of Medicine Faculty Research

Exogenous lipoid pneumonia is a rare and frequently misdiagnosed lung disease. It occurs as an inflammatory reaction secondary to either aspiration or inhalation of lipids. Our patient had a history significant for recurrent pneumonia and the use of mineral oil for chronic constipation. A chest computed tomography showed multifocal consolidative opacities with areas of low attenuation, highly suspicious of exogenous lipid pneumonia. The diagnosis was confirmed with combined bronchoalveolar lavage and transbronchial lung biopsy that showed lipid-laden macrophages consistent with exogenous lipoid pneumonia. After thorough medication review, apart from mineral oil, no other contributing factors were found. A diagnosis of …

Phosphodiesterase Isoforms And Camp Compartments In The Development Of New Therapies For Obstructive Pulmonary Diseases, Martina Schmidt, Isabella Cattani-Cavalieri, Francisco J. Nuñez, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

The second messenger molecule 3′5′-cyclic adenosine monophosphate (cAMP) imparts several beneficial effects in lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). While cAMP is bronchodilatory in asthma and COPD, it also displays anti-fibrotic properties that limit fibrosis. Phosphodiesterases (PDEs) metabolize cAMP and thus regulate cAMP signaling. While some existing therapies inhibit PDEs, there are only broad family specific inhibitors. The understanding of cAMP signaling compartments, some centered around lipid rafts/caveolae, has led to interest in defining how specific PDE isoforms maintain these signaling microdomains. The possible altered expression of PDEs, and thus abnormal …

Modulator Therapy For Cystic Fibrosis: An Exploration Of Current Research, Jessalyn Rombocos

Senior Honors Theses

Developing a drug therapy that addresses the root cause of cystic fibrosis (CF) by increasing CFTR protein levels has long been a research challenge. After genetic therapy failed because a suitable delivery system could not be found, researchers began searching for small organic molecules that could act as chaperones for CFTR. These molecules, known as modulators, allowed CFTR to be assembled correctly and function similarly to wild type CFTR. Since 2012, four modulator drugs have been developed, tested, and approved by the FDA. In October 2019, Trikafta was approved as the first triple-combination modulator drug and has completely revolutionized CF …

Hsp90 Inhibitors For Ipf/Covid-19, Ruben Manuel Luciano Colunga Biancatelli, Pavel A. Solopov, John Catravas

Bioelectrics Publications

Heat shock protein 90 (HSP90) is an important chaperone that assists the late stage folding of several proteins involved in cell survival in response to environmental stressors. The inhibition of HSP90 is followed by a complex modulation of the proteome and the kinome, that has proved beneficial in cancer and various neurodegenerative diseases. Additionally, accumulating literature suggests that HSP90 may be a key target during the development of pulmonary fibrosis and that its inhibition could serve as a new and exciting therapeutic approach. We have summarized the current evidence about HSP90’s role in Idiopathic Pulmonary Fibrosis (IPF), the results from …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Reply To Lipworth Et Al., Angela M. Moran, Sanjay Ramakrishnan, Catherine A. Borg, Clare M. Connolly, Simon Couillard, Christine M. Mwasuku, Ian D. Pavord, Timothy S.C. Hinks, Lauri Lehtimӓki

Research outputs 2014 to 2021

We thank Dr. Lipworth and colleagues for their interest in our work published recently in the Journal (1). They rightly point out that the biology of asthma attacks is more complex than blood eosinophils alone and that corticosteroids have a wide range of other potentially relevant antiinflammatory effects. However, local treatment with inhaled corticosteroids (ICS) is usually the mainstay of patients with frequent eosinophilic exacerbations, and therefore in the great majority of patients, the key question is what oral corticosteroids (OCS) add to ICS in an acute attack (2) and whether this effect is seen with benralizumab. We suggest that …

Budesonide Enhances Agonist-Induced Bronchodilation In Human Small Airways By Increasing Camp Production In Airway Smooth Muscle, Cynthia J. Koziol-White, Timothy B. Johnstone, Maia L. Corpuz, Gaoyuan Cao, Sarah Orfanos, Vishal Parikh, Brian Deeney, Omar Tliba, Rennolds S. Ostrom, Ian Dainty, Reynold A. Panettieri Jr.

Pharmacy Faculty Articles and Research

The non-genomic mechanisms by which glucocorticoids modulate β₂ agonist-induced-bronchodilation remain elusive. Our studies aimed to elucidate mechanisms mediating the beneficial effects of glucocorticoids on agonist-induced bronchodilation. Utilizing human precision cut lung slices (hPCLS), we measured bronchodilation to formoterol, prostaglandin E₂ (PGE₂), cholera toxin (CTX) or forskolin in the presence and absence of budesonide. Using cultured human airway smooth muscle (HASM), intracellular cAMP was measured in live cells following exposure to formoterol, PGE₂, or forskolin in the presence or absence of budesonide. We showed that simultaneous budesonide administration amplified formoterol-induced bronchodilation and attenuated agonist-induced phosphorylation …

Navigating A Difficult Transition In Pulmonary Arterial Hypertension: A Clinical Case Study, Tina Hyman, Michael Salinero, Francisco Javier Jimenez-Carcamo, Margarita Pallares, Maribel Matos

Nursing & Health Sciences Research Journal

Over the past 20 years, Pulmonary Arterial Hypertension (PAH) patients and providers have seen an increase in options to treat PAH. Currently, there are choices for the delivery of medications approved to treat patients with PAH where at one point the only option was intravenous (IV) therapy. This case study details the transition from IV Epoprostenol to oral Treprostinil for the treatment of a 53 year old female diagnosed with severe Pulmonary Arterial Hypertension whose quality of life became unbearable by the IV medication delivery route. This patient was a synchronized swimmer in her youth and her passion for water …

The Wet Bridge Transfer System: An Novel In Vitro Tool For Assessing Exogenous Surfactant As A Pulmonary Drug Delivery Vehicle, Brandon J. Baer

Western Research Forum

Background:

Due to its complex branching structure, direct drug delivery to the remote areas of the lung is a major challenge. Consequently, most therapies, such as those treating pulmonary infection and inflammation, must utilize large systemic dosing, with the potential for adverse side effects. A novel alternative strategy is to use exogenous surfactant, a material capable of distributing throughout the lung, as a pulmonary drug delivery vehicle.

Objective:

Utilize an in vitro transferring system to assess exogenous surfactant (BLES) as a pulmonary delivery vehicle for different therapeutics.

Methods:

An in vitro technique was developed to simultaneously study surfactant delivery and …

Iron-Containing Nanoparticles For The Treatment Of Chrionic Biofilm Infections In Cystic Fibrosis, Leisha M. A. Martin

Nanoscience and Microsystems ETDs

Cystic fibrosis (CF) is the most common genetic disease resulting in the morbidity and mortality of Caucasian children and adults worldwide. Due to a genetic mutation resulting in malfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, CF patients produce highly viscous mucus in their respiratory tract. This leads to impairment of the mucociliary clearance of inhaled microbes. In addition to reduced microbial clearance, anoxic environmental conditions in the lungs promote biofilm-mode growth of the pathogenic bacterial species Pseudomonas aeruginosa. Chronic infections of P. aeruginosa begin in early childhood and typically persist until respiratory failure and death result. The …

Transforming Growth Factor-Β1 Decreases Β2-Agonist–Induced Relaxation In Human Airway Smooth Muscle, Christie A. Ojiaku, Elena Chung, Vishal Parikh, Jazmean K. Williams, Anthony Schwab, Ana Lucia Fuentes, Maia L. Corpuz, Victoria Lui, Sam Paek, Natalia M. Bexiga, Shreya Narayan, Francisco J. Nunez, Kwangmi An, Rennolds S. Ostrom, Steven S. An, Reynold A. Pannettieri Jr.

Pharmacy Faculty Articles and Research

Helper T effector cytokines implicated in asthma modulate the contractility of human airway smooth muscle (HASM) cells. We have reported recently that a profibrotic cytokine, transforming growth factor (TGF)-β1, induces HASM cell shortening and airway hyperresponsiveness. Here, we assessed whether TGF-β1 affects the ability of HASM cells to relax in response to β₂-agonists, a mainstay treatment for airway hyperresponsiveness in asthma. Overnight TGF-β1 treatment significantly impaired isoproterenol (ISO)-induced relaxation of carbachol-stimulated, isolated HASM cells. This single-cell mechanical hyporesponsiveness to ISO was corroborated by sustained increases in myosin light chain phosphorylation. In TGF-β1–treated HASM cells, ISO evoked markedly lower …

Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel

Pharmaceutical Sciences Faculty Publications

Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized …

A Cytotoxic Evaluation Of A Chalcone Derivative Library On A549 Cells, Mary Elaine Kuo

Undergraduate Theses

Chalcones, a precursor to flavonoids, are chemical compounds found naturally in plants. The chalcones’ structure consists of a ketone bridge attached to two aromatic rings. Varying substituents on the aromatic rings allow for different affects, including anti-cancer properties. As a Michael acceptor, chalcones interact with pathways that cause inhibition of the initiation, promotion, and progression of cancer tumors. We have screened 32 compounds for growth inhibition in lung cells that vary the flexibility and confirmation of the 3 carbon bridge between the two aromatic rings as well as the effects of electronic modifications to the aromatic ring. We have found …

Sustainability And Outcomes Of A Standardized Aminoglycoside Induced Ototoxicity Monitoring Algorithm, Claire Elson, Christopher M. Oermann, Michelle Weltman, Ellen Meier

Posters

No abstract provided.

The Role Of Ceramide In Neutrophil Elastase Induced Inflammation In The Lungs, Sophia Karandashova

Theses and Dissertations

Alterations to sphingolipid metabolism are associated with increased pulmonary inflammation, but the impact of inflammatory mediators, such as neutrophil elastase (NE), on airway sphingolipid homeostasis remains unknown. NE is a protease associated CF lung disease progression, and can be found in up to micromolar concentrations in patient airways. While sphingolipids have been investigated in the context of CF, the focus has been on loss of cystic fibrosis transmembrane conductance regulator (CFTR) function. Here, we present a novel observation: oropharyngeal aspiration of NE increases airway ceramides in mice. Using a previously characterized mouse model of NE-induced inflammation, we demonstrate that NE …

Successful Reversal Of Furosemide-Induced Secondary Hyperparathyroidism With Cinacalcet., Tarak Srivastava, Shahryar Jafri, William E. Truog, Judith Sebestyen Vansickle, Winston M. Manimtim, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Secondary hyperparathyroidism (SHPT) is a rare complication of furosemide therapy that can occur in patients treated with the loop diuretic for a long period of time. We report a 6-month-old 28-weeks premature infant treated chronically with furosemide for his bronchopulmonary dysplasia, who developed hypocalcemia and severe SHPT, adversely affecting his bones. Discontinuation of the loop diuretic and the addition of supplemental calcium and calcitriol only partially reversed the SHPT, bringing serum parathyroid hormone level down from 553 to 238 pg/mL. After introduction of the calcimimetic Cinacalcet, we observed a sustained normalization of parathyroid hormone concentration at 27 to 63 pg/mL …

Rock2 Gene Single Nucleotide Polymorphisms And Association With Bronchopulmonary Dysplasia In Extremely Low Birth Weight Infants, Sharina Rajbhandari, Asma Amin, Shaili Amatya, Leewen Hsu, Anna Zylak, Umesh Paudel, Lance A. Parton

NYMC Faculty Posters

No abstract provided.

Are Gene Polymorphisms Of Fibroblast Growth Factor 10 Associated With Patent Ductus Arteriosus And Bronchopulmonary Dysplasia In Extremely Low Birth Weight Infants?, Shaili Amatya, Asma Amin, Umesh Paudel, Lance A. Parton

NYMC Faculty Posters

No abstract provided.

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …