Medical Sciences Commons^™

The Effect Of Heparinoid As Systemic Prophylactic Anticoagulants On Covid-19 Patient Mortality And Its Safety Profiles: A Systematic Review And Meta-Analysis, Ariska Deffy Anggarany, Rani Sauriasari, Muhammad Alkaff, Famila Takhwifa, Hayatun Nufus, Diana Paramita

Pharmaceutical Sciences and Research

Coagulopathy is one of the complications of COVID-19 and is associated with a higher risk of mortality. However, evidence regarding the effectiveness and safety of anticoagulant therapy in various doses among COVID-19 patients is limited. This systematic review and meta-analysis aims to review and explore the effect of using heparinoids as a systemic anticoagulant at prophylactic doses on mortality in COVID-19 patients. Systematic searches were conducted of various databases (Pubmed, ScienceDirect, SpringerLink, Scopus, and ProQuest) covering the period 2019-2021. We assessed the quality of the articles using the STROBE checklist. Studies with a high risk of bias were excluded before …

The Benefits Of Astaxanthin To Improve Pain Relief In Patients With Painful Diabetic Neuropathy: An Open-Label, Randomized Controlled Trial, Rizaldy Taslim Pinzon, Mary Rose Angelina Budi Harsana

Pharmaceutical Sciences and Research

Treatment of diabetic neuropathy is still carried out by providing symptomatic therapy, which only improves ± 50% of the total symptoms felt by patients, but does not tackle the underlying causes of the disease. Astaxanthin is a potent antioxidant, anti-inflammatory, and anti-diabetic carotenoid that could be an additional treatment option. We aimed to measure the effectiveness of administering astaxanthin as an additional therapy to improve the impact of pain and discomfort experienced daily by diabetes mellitus patients with painful diabetic neuropathy. We conducted a randomized experimental study with an open label design of 36 patients who had been diagnosed with …

A Snapshot Investigation Into The Availability And Access To Codeine-Containing Medications Amongst The Irish Population., Katie O'Brien, Pádraig Mckeown, Joseph Phelan

International Undergraduate Journal of Health Sciences

Codeine phosphate is a mild to moderate analgesic and has a weak cough suppressant activity that is available to purchase as an over the counter (OTC) painkiller in Ireland as a compound product. In recent years, countries such as Australia have introduced laws that prohibit the sale of the drug without a valid prescription. This move by Australia begs the question as to why this legislation was introduced and should Ireland follow suit.

The primary aims of the study were to determine knowledge among the general public of codeine-containing medications and their usage levels. The survey also investigated whether current …

Recombinant Human Proteoglycan 4 Regulates Phagocytic Activation Of Monocytes And Reduces Il-1Β Secretion By Urate Crystal Stimulated Gout Pbmcs, Sandy Elsayed, Gregory D. Jay, Ralph Cabezas, Marwa Qadri, Tannin A. Schmidt, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Objectives

To compare phagocytic activities of monocytes in peripheral blood mononuclear cells (PBMCs) from acute gout patients and normal subjects, examine monosodium urate monohydrate (MSU) crystal-induced IL-1β secretion ± recombinant human proteoglycan 4 (rhPRG4) or interleukin-1 receptor antagonist (IL-1RA), and study the anti-inflammatory mechanism of rhPRG4 in MSU stimulated monocytes.

Methods

Acute gout PBMCs were collected from patients in the Emergency Department and normal PBMCs were obtained from a commercial source. Monocytes in PBMCs were identified by flow cytometry. PBMCs were primed with Pam3CSK4 (1μg/mL) for 24h and phagocytic activation of monocytes was determined using fluorescently labeled latex beads. MSU …

Characterizing And Overcoming Resistance To Aminomethylspectinomycins In Gram-Negative Bacteria, Nisha Das

Theses and Dissertations (ETD)

Spectinomycin (SPC) is a broad-spectrum aminocyclitol antibiotic. Its use in agriculture has led to widespread resistance in enteric bacteria, necessitating the development of more effective analogs. Aminomethyl spectinomycins (amSPC) are modified spectinomycins with increased potency against many bacterial species. These species include Legionella pneumophila, which harbors a chromosomally encoded aminoglycoside modifying enzyme (AME). In this study, we follow up on this observation and examine the extent to which the amSPCs are substrates for AMEs through adenylation (ANTs) and phosphorylation (APH). APH(9)-Ia and ANT(3")(9) were expressed in E. coli BL21(DE3) and purified using the Ni-affinity chromatography. The ability of AMEs to …

Comparative Metabolism Of Aflatoxin B1 In Two Quail Genera Coturnix Japonica And Callipepla Californica, Sean Moody

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

Avian species are highly susceptible to the hepatotoxic mycotoxin aflatoxin B₁ (AFB₁). Domesticated turkeys are exquisitely sensitive, due to a combination of highly-efficient hepatic cytochrome P450 (CYP)-mediated bioactivation, and to dysfunctional alpha-class glutathione S-transferases (GSTAs) which typically detoxify the bioactivated electrophilic metabolite exo-AFB₁-8,9-epoxide (AFBO). Wild turkeys are relatively resistant to AFB₁ in large part due to expression of functional GSTAs. Quail, a related Galliforme, are slightly less sensitive in vivo to AFB₁, but whether this is related to the hepatic metabolic profiles of these two critical enzymes has not been rigorously evaluated. …

Modulating The Tumor Microenvironment To Improve Immunotherapy Treatments, Lleayem Nazario-Johnson, David Rowley

Senior Honors Projects

Advances in immunotherapy are revolutionizing the treatments of certain cancers, especially those in the blood. However, wider applications for eradicating solid tumors have been slow to emerge. A likely reason is the presence of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment that secrete immunosuppressive molecules which attenuate the attack of immune cells. We hypothesize that small molecule Wnt/Beta- Catenin inhibitors can be used to modulate the immunosuppressive actions of MDSCs and increase the effectiveness of immunotherapy treatments, such as with chimeric antigen receptor (CAR) T-cells. The Wnt/Beta-Catenin Pathway has been shown to be a crucial driving force behind the …

Physiological Roles Of Mammalian Transmembrane Adenylyl Cyclase Isoforms, Katrina F. Ostrom, Justin E. Lavigne, Tarsis F. Brust, Roland Seifert, Carmen Dessauer, Val J. Watts, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Adenylyl cyclases (ACs) catalyze the conversion of ATP to the ubiquitous second messenger cAMP. Mammals possess nine isoforms of transmembrane ACs, dubbed AC1-9, that serve as major effector enzymes of G protein-coupled receptors. The transmembrane ACs display varying expression patterns across tissues, giving potential for them having a wide array of physiologic roles. Cells express multiple AC isoforms, implying that ACs have redundant functions. Furthermore, all transmembrane ACs are activated by Gα_s so it was long assumed that all ACs are activated by Gα_s-coupled GPCRs. AC isoforms partition to different microdomains of the plasma membrane and form …

Long-Term Survival Of Older Patients Hospitalized For Covid-19. Do Clinical Characteristics Upon Admission Matter?, Michał Chojnicki, Agnieszka Neumann-Podczaska, Mikołaj Seostianin, Zofia Tomczak, Hamza Tariq, Jerzy Chudek, Sławomir Tobis, Iwona Mozer-Lisewska, Aleksandra Suwalska, Andrzej Tykarski, Piotr Merks, Sylwia Kropińska, Małgorzata Sobieszczańska, Frank Romanelli, Katarzyna Wieczorowska-Tobis

Pharmacy Practice and Science Faculty Publications

Older adults are particularly susceptible to COVID-19 in terms of both disease severity and risk of death. To compare clinical differences between older COVID-19 hospitalized survivors and non-survivors, we investigated variables influencing mortality in all older adults with COVID-19 hospitalized in Poznań, Poland, through the end of June 2020 (n = 322). In-hospital, post-discharge, and overall 180-day mortality were analyzed. Functional capacity prior to COVID-19 diagnosis was also documented. The mean age of subjects was 77.5 ± 10.0 years; among them, 191 were females. Ninety-five (29.5%) died during their hospitalization and an additional 30 (9.3%) during the post-discharge period …

Collagen-Based Biomaterials With Possible Therapeutic Effects, Ramona Mihaela Nedelcuţă, Gigi Călin, Mihai Cristian Nedelcuţă, Vlad Dumitru Baleanu, Dragos Virgil Davitoiu, Bogdan Socea, Bogdan-Petre Stănoiu

Journal of Mind and Medical Sciences

Epidermolysis bullosa (EB) is a rare, serious genetic disease, incurable through the current means. Apart from this initial definition, there was later some ease in the definition of the disease, including the manifestations of toxic epidermal necrolysis and Stevens Johnson syndrome in this entity. In medical practice, there are cases that do not overlap with the description in the literature, thus the treatment must be adapted and personalized to the particularities. We present the case of a female new-born, with "de novo" mutation for the early-onset antenatal epidermolysis and our personalized therapeutic management, based on collagen from bovine corneas by …

Exogenous Surfactant As A Delivery Vehicle For Intrapulmonary Therapeutics, Brandon J. Baer

Electronic Thesis and Dissertation Repository

As an organ system, the lung has unique advantages and disadvantages for direct drug delivery. Its contact with the external environment allows for the airways to be easily accessible to intrapulmonary delivery. However, its complex structure, which divides into more narrow airways with each branch, can make direct delivery to the remote alveoli challenging. The objective of this thesis was to overcome this issue by using exogenous surfactant, a lipoprotein complex used to treat neonatal respiratory distress syndrome, as a carrier for pulmonary therapeutics. It was hypothesized that therapeutics administered with a surfactant vehicle would display enhanced delivery to the …

Can 3d Printers Create Viable Personalized Therapy In The Treatment Of Diabetes?, Lyla White

Holster Scholar Projects

This study aimed to use 3D printing techniques to create a drug tablet containing two commonly used active ingredients (metformin and glyburide) for treating diabetes in a single pill. The hypothesis was that both drugs can be given in doses not available commercially and that these pills will have appropriate hardness, and extended-release dissolution. I was able to create 48 tablets that contained evenly dispersed active ingredient powder and met the weight requirements with consistency between tablets. Unfortunately, we had to substitute the usual bulk excipient for another because it was incompatible with the metformin and the replacement (mannitol) may …

Local Renin-Angiotensin System Activation And Myofibroblast Formation In Graft Versus Host Disease–Associated Conjunctival Fibrosis, Kiumars Shamloo, Judy Weng, Christopher Ross, Jenni Lee, Saleh Alfuraih, Jennifer Totonchy, Ajay Sharma

Pharmacy Faculty Articles and Research

Purpose: The present study was designed to investigate the role of myofibroblast transdifferentiation and the conjunctival renin–angiotensin system (RAS) in the pathogenesis of graft-versus-host disease (GVHD)–associated conjunctival fibrosis.

Methods: A mouse model of major histocompatibility-matched allogeneic transplantation was used to induce GVHD, with male B10.D2 mice as donors and female BALB/c mice as recipients. Male BALB/c to female BALB/c syngeneic transplantation was used as control. Y chromosome staining in the spleen cells obtained from female recipient mice was used to confirm engraftment. The phenol red thread test and fluorescein staining were used to quantify tears and corneal keratopathy. …

A Comparison Of Calcium Aggregation And Ultracentrifugation Methods For The Preparation Of Rat Brain Microsomes For Drug Metabolism Studies, Barent N. Dubois, Farideh Amirrad, Reza Mehvar

Pharmacy Faculty Articles and Research

Preparation of brain microsomes by the calcium chloride aggregation method has been suggested as an alternative to the ultracentrifugation method. However, the effects of the calcium chloride concentration on the quality of the microsomal fractions are not known. Brain microsomes were prepared from the adult rat brains using the high-speed ultracentrifugation and low-speed calcium chloride (10–100 mM) aggregation methods (n = 5–6 per group). The microsomal protein yield (spectrometry), the cytochrome P450 reductase (CPR) activity (spectrometry), and the monooxygenase activities (UPLC-MS/MS) of CYP2D and CYP2E1 were determined in the obtained fractions. Increasing the concentrations of calcium chloride progressively increased …

Decreasing Unintentional Pregnancies For Tennesseans, Paula M. Todd

Electronic Theses and Dissertations

In 2018, 49% of all pregnancies in the United States were unintended, with women with a lower- income status being five times more likely to experience an unplanned pregnancy. Tennessee has a high rate of unintended pregnancies, particularly among the uninsured, low-income, and rural teen populations; some 22% of these unintended pregnancies end in abortion. Oral or transdermal contraceptives that are affordable and accessible for women of childbearing age can reduce unintentional pregnancies. The addressed gap in clinical practice was that contraceptives are not currently available over the counter in Tennessee pharmacies without a prescription, which necessitates a costly medical …

Clinical Implications Of Combinatorial Pharmacogenomic Tests Based On Cytochrome P450 Variant Selection, Michael R. Sayer, Ashley Duche, Trang Jenny Tran Nguyen, Michelle Le, Kunj Patel, Jacqueline Vu, Danny Pham, Brianne Vernick, Richard Beuttler, Don Roosan, Moom R. Roosan

Pharmacy Faculty Articles and Research

Despite the potential to improve patient outcomes, the application of pharmacogenomics (PGx) is yet to be routine. A growing number of PGx implementers are leaning toward using combinatorial PGx (CPGx) tests (i.e., multigene tests) that are reusable over patients’ lifetimes. However, selecting a single best available CPGx test is challenging owing to many patient- and population-specific factors, including variant frequency differences across ethnic groups. The primary objective of this study was to evaluate the detection rate of currently available CPGx tests based on the cytochrome P450 (CYP) gene variants they target. The detection rate was defined as the percentage of …

Endophytes Of Brazilian Medicinal Plants With Activity Against Phytopathogens, Jucélia Iantas, Daiani Cristina Savi, Renata Da Silva Schibelbein, Sandriele Aparecida Noriler, Beatriz Marques Assad, Guilherme Dilarri, Henrique Ferreira, Jürgen Rohr, Jon S. Thorson, Khaled A. Shaaban, Chirlei Glienke

Pharmaceutical Sciences Faculty Publications

Plant diseases caused by phytopathogens are responsible for significant crop losses worldwide. Resistance induction and biological control have been exploited in agriculture due to their enormous potential. In this study, we investigated the antimicrobial potential of endophytic fungi of leaves and petioles of medicinal plants Vochysia divergens and Stryphnodendron adstringens located in two regions of high diversity in Brazil, Pantanal, and Cerrado, respectively. We recovered 1,304 fungal isolates and based on the characteristics of the culture, were assigned to 159 phenotypes. One isolate was selected as representative of each phenotype and studied for antimicrobial activity against phytopathogens. Isolates with better …

Subtype-Selective Positive Modulation Of KCa 2 Channels Depends On The Ha/Hb Helices, Young-Woo Nam, Meng Cui, Naglaa Salem, Razan Orfali, Misa Nguyen, Grace Yang, Mohammad Asikur Rahman, Judy Lee, Miao Zhang

Pharmacy Faculty Articles and Research

Background and Purpose

In the activated state of small-conductance Ca2+-activated potassium (KCa 2) channels, calmodulin interacts with the HA/HB helices and the S4-S5 linker. CyPPA potentiates KCa 2.2a and KCa 2.3 channel activity but not the KCa 2.1 and KCa 3.1 subtypes.

Experimental Approach

Site-directed mutagenesis, patch-clamp recordings and in silico modeling were utilized to explore the structural determinants for the subtype-selective modulation of KCa 2 channels by CyPPA.

Key Results

Mutating residues in the HA (V420) and HB (K467) helices of KCa 2.2a channels to their equivalent residues in KCa 3.1 channels diminished the potency of CyPPA. CyPPA elicited …

Point Substitutions In G Protein-Coupled Receptors, Jessica Brown

Undergraduate Student Research Internships Conference

G protein-coupled receptors (GPCRs) are proteins that are important in physiological regulatory processes within the body, and for this reason are important drug targets. When bound to an agonist, such as neurotransmitters or hormones, the receptor adopts an active state to allow these biochemical pathways to occur. However, mutations can arise within the receptor that affect its ability to bind its agonist. This natural variation found within the genome can make it difficult to design pharmaceuticals to target the receptors.

To see the effects of these point substitutions on agonist-induced receptor activation, mutations were made within a negative allosteric site …

Urinary Bile Acid Indices As Prognostic Biomarkers For The Complications Of Liver Diseases, Wenkuan Li

Theses & Dissertations

Hepatobilary diseases cause the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues, which may lead to an unfavorable prognosis. In this study, we compared the urinary BA profile in 257 patients with hepatobilary diseases during a 7-year follow-up period. We investigated the use of the urinary BA profile to develop logistic regression models to predict the prognosis of hepatobiliary diseases in terms of developing disease-related complications, especially for ascites. The urinary BA profile was characterized by calculating BA indices, which quantify the composition, metabolism, hydrophilicity, and toxicity of the BA profile. All patients had high …

Uplc-Ms/Ms Analysis Of The Michaelis-Menten Kinetics Of Cyp3a-Mediated Midazolam 1′- And 4-Hydroxylation In Rat Brain Microsomes, Devaraj Venkatapura Chandrashekar, Barent Dubois, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ) is a short-acting benzodiazepine with rapid onset of action, which is metabolized by CYP3A isoenzymes to two hydroxylated metabolites, 1′-hydroxymidazolam and 4-hydroxymidazolam. The drug is also commonly used as a marker of CYP3A activity in the liver microsomes. However, the kinetics of CYP3A-mediated hydroxylation of MDZ in the brain, which contains much lower CYP content than the liver, have not been reported. In this study, UPLC-MS/MS and metabolic incubation methods were developed and validated for simultaneous measurement of low concentrations of both hydroxylated metabolites of MDZ in brain microsomes. Different concentrations of MDZ (1–500 µM) were incubated with …

Insights Into The Mechanisms Of Brain Endothelial Erythrophagocytosis, Jiahong Sun, Prema Vyas, Samar Mann, Annlia Paganini-Hill, Ane C. F. Nunes, Wei Ling Lau, David H. Cribbs, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium in vivo and in vitro, in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis. Murine brain microvascular endothelial cells (bEnd.3 …

The Experience Of Off Periods In Parkinson’S Disease: Descriptions, Triggers, And Alleviating Factors, Sneha Mantri, Madeline Lepore, Briana Edison, Margaret Daeschler, Catherine Kopil, Connie Marras, Lana Chahine

Journal of Patient-Centered Research and Reviews

Purpose: Wearing off of Parkinson’s disease medication is common, but triggers and coping strategies for this transient phenomenon are poorly understood. We aimed to assess the lived experience of OFF periods for people with Parkinson’s disease.

Methods: Participants in the longitudinal Fox Insight study who endorsed OFF periods were invited to complete a survey consisting of both multiple-choice and free-text responses. Descriptive statistics were used to summarize multiple-choice responses, and free-text responses were classified into themes through iterative discussion by 3 movement disorders specialists.

Results: A total of 2110 participants (52.4% male) completed the survey. Tremor was the most common …

Differential Effect Of Proinflammatory Cytokines On Corneal And Conjunctival Epithelial Cell Mucins And Glycocalyx, Kiumars Shamloo, Priya Mistry, Ashley Barbarino, Christopher Ross, Vishal Jhanji

Pharmacy Faculty Articles and Research

Purpose: Ocular surface mucins and glycocalyx are critical for providing ocular hydration as well lubrication and repelling pathogens or allergens. Elevated levels of tear proinflammatory cytokines in dry eye may have detrimental effect on mucins and glycocalyx. The present study tested the effect of proinflammatory cytokines IL-6, TNF-α, and IFN-γ on membrane-tethered mucins expression, glycocalyx, and viability of ocular surface epithelial cells.

Methods: Stratified cultures of human corneal and conjunctival epithelial cells were exposed to different concentrations of IL-6, TNF-α, and IFN-γ for 24 hours. The mucins gene and protein expressions were quantified by real-time polymerase chain reaction …

Candida Cell-Surface-Specific Monoclonal Antibodies Protect Mice Against Candida Auris Invasive Infection, Jonothan Rosario-Colon, Karen Eberle, Abby Adams, Evan Courville, Hong Xin

School of Graduate Studies Faculty Publications

Candida auris is a multidrug-resistant fungal pathogen that can cause disseminated bloodstream infections with up to 60% mortality in susceptible populations. Of the three major classes of antifungal drugs, most C. auris isolates show high resistance to azoles and polyenes, with some clinical isolates showing resistance to all three drug classes. We reported in this study a novel approach to treating C. auris disseminated infections through passive transfer of monoclonal antibodies (mAbs) targeting cell surface antigens with high homology in medically important Candida species. Using an established A/J mouse model of disseminated infection that mimics human candidiasis, we showed that …

Evaluation Of Somatic Mutations In Solid Metastatic Pan-Cancer Patients, Moom Roosan, Isa Mambetsariev, Rebecca Pharaon, Jeremy Fricke, Angel R. Baroz, Joseph Chao, Chen Chen, Mohd W. Nasser, Ramakanth Chirravuri-Venkata, Maneesh Jain, Lynette Smith, Susan E. Yost, Karen L. Reckamp, Raju Pillai, Leonidas Arvanitis, Michelle Afkhami, Edward W. Wang, Vincent Chung, Mihaela Cristea, Marwan Fakih, Marianna Koczywas, Erminia Massarelli, Joanne Mortimer, Yuan Yuan, Surinder K. Batra, Sumanta Pal, Ravi Salgia

Pharmacy Faculty Articles and Research

Metastasis continues to be the primary cause of all cancer-related deaths despite the recent advancements in cancer treatments. To evaluate the role of mutations in overall survival (OS) and treatment outcomes, we analyzed 957 metastatic patients with seven major cancer types who had available molecular testing results with a FoundationOne CDx^® panel. The most prevalent genes with somatic mutations were TP53, KRAS, APC, and LRP1B. In this analysis, these genes had mutation frequencies higher than in publicly available datasets. We identified that the somatic mutations were seven mutually exclusive gene pairs and an additional fifty-two co-occurring gene pairs. Mutations …

Antibiotic Tolerance And Heteroresistance: Associated Fitness Costs And Potential In Evading Antibiotic Killing, Tina H. Dao

Theses and Dissertations (ETD)

Streptococcus pneumoniae is a prominent human pathogen that causes both invasive and non-invasive diseases, such as otitis media, pneumonia, meningitis, and bacteremia. Although it is frequently an asymptomatic colonizer of the human nasopharynx, S. pneumoniae is a major cause of morbidity and mortality in the immune compromised population, young children, and the elderly. Up until the 1970s, S. pneumoniae was susceptible to almost all antibiotics. Since then, this pathogen has gained resistance to a variety of antibiotic treatments, including beta-lactams, macrolides, and fluoroquinolones.

In the first chapter, we focused on fluoroquinolone resistance in S. pneumoniae. Fluoroquinolones are one of the …

Critically Ill Covid-19 Patients Exhibit Anti-Sars-Cov-2 Serological Responses, Mark Daley, Douglas D. Fraser, Gediminas Cepinskas, Marat Slessarev, Claudio M. Martin, Maitray A. Patel, Michael Miller, Eric K. Patterson, David B. O’Gorman, Sean E. Gill, Ian Higgins, Julius P. John, Christopher Melo, Lylia Nini, Xiaoqin Wang, Johannes Zeidler, Jorge A. Cruz-Aguado

Physiology and Pharmacology Publications

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is a global health care emergency. Anti-SARS-CoV-2 serological profiling of critically ill COVID-19 patients was performed to determine their humoral response. Blood was collected from critically ill ICU patients, either COVID-19 positive (+) or COVID-19 negative (−), to measure anti-SARS-CoV-2 immunoglobulins: IgM; IgA; IgG; and Total Ig (combined IgM/IgA/IgG). Cohorts were similar, with the exception that COVID-19+ patients had a greater body mass indexes, developed bilateral pneumonias more frequently and suffered increased hypoxia when compared to COVID-19-patients (p < 0.05). The mortality rate for COVID-19+ patients was 50%. COVID-19 status could be determined by anti-SARS-CoV-2 serological responses with excellent classification accuracies on ICU day 1 (89%); ICU day 3 (96%); and ICU days 7 and 10 (100%). The importance of each Ig isotype for determining COVID-19 status on combined ICU days 1 and 3 was: Total Ig, 43%; IgM, 27%; IgA, 24% and IgG, 6%. Peak serological responses for each Ig isotype occurred on different ICU days (IgM day 13 > IgA day 17 > IgG persistently increased), with the Total Ig peaking at approximately ICU day …

Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-Β Associated Neurodegenerative Pathways And Glial Signatures In A Mouse Model Of Alzheimer’S Disease: A Targeted Transcriptome Analysis, Chao Ma, Jerry B. Hunt, Andrii Kovalenko, Huimin Liang, Maj-Linda B. Selenica, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer’s disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 (Arg1) is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them. Altered arginine metabolism is proposed as a new biomarker pathway for AD. We previously reported Arg1 deficiency in myeloid biased cells using lysozyme M (LysM) promoter-driven deletion worsened amyloidosis-related neuropathology and behavioral impairment. However, …

Lipoxin A 4 (Lxa 4 ) Promotes Reduction And Antibiotic Efficacy Against Pseudomonas Aeruginosa Biofilm, Julianne M. Thornton, Jean Walker, Prem Y.K. Sundarasivarao, Bernd Spur, Ana Rodriguez, Kingsley Yin

Rowan-Virtua Research Day

Pseudomonas aeruginosa (P aeruginosa) is an opportunistic bacterium commonly found in wound infections and airways of cystic fibrosis patients P aeruginosa readily forms biofilms which can reduce the efficacy of antibiotics used to eradicate the pathogen We have previously shown that a Specialized Pro resolving Mediator ( Lipoxin A 4 (LxA 4 is a quorum sensing inhibitor which can reduce P aeruginosa virulence In this study, we examined the direct actions of LxA 4 and RvD 2 on P aeruginosa biofilm formation and virulence gene expression The influence of LxA 4 on antibiotic efficacy and the combined effects on biofilm …