Pharmacy and Pharmaceutical Sciences Commons^™

Great Expectations: Phosph(On)Ate Prodrugs In Drug Design—Opportunities And Limitations, Victoria Yan

Dissertations and Theses (Open Access)

Phosphate and phosphonates are chemical moieties with historical precedence in anticancer and antiviral nucleotide analogues. Synchronous to modern efforts identifying novel therapeutic targets in cancer, such chemical moieties are being investigated in the design of novel inhibitors with antineoplastic potential. A central challenge to the delivery of phosph(on)ate-containing drugs is their anionic character at physiological pH, which portends poor membrane permeability. This limitation has been successfully overcome through the use of prodrugs. When attached to the phosph(on)ate moiety, prodrugs mask the negative charge and easily enable cell permeability. Upon cellular entry, the promoieties are enzymatically or environmentally cleaved to unveil …

Veru-111 As An Oral Tubulin Inhibitor Suppressing Triple-Negative Breast Cancer And Evaluation Of Novel Tubulin Inhibitors For Cancer Therapy, Shanshan Deng

Theses and Dissertations (ETD)

Triple negative breast cancer (TNBC) has aggressive clinical features strongly associated with poorer overall prognosis and higher mortality rates relative to other molecular subtypes. FDA-approved drugs, such as paclitaxel, are effective in treating TNBC. Yet, treatment failure is commonly observed due to the development of acquired chemoresistance, which remains a clinical challenge for TNBC therapy.

Vitamin D Levels Affect Survival In A Bcr-Abl Acute Lymphoblastic Leukemia Mouse Model But Do Not Cause Vitamin-Drug Interactions, Kavya Annu

Theses and Dissertations (ETD)

It is a well-established phenomenon that dietary components containing CYP3A inducers or inhibitors if co-administered with drugs that are CYP3A4 substrates lead to marked drug-drug interactions. Because vitamin D is known to regulate intestinal CYP3A expression and gut CYP3A expression plays an important role in pre-systemic metabolism of CYP3A drugs, we determined the impact of vitamin D (VD3) status on systemic exposure and efficacy of chemotherapeutic agents that are CYP3A substrates. We employed VD3 sufficient and deficient mice to perform pharmacokinetics (PK) and anti-leukemic efficacy studies.

First, using hCYP3A4 transgenic mouse model we evaluated the intestinal, hepatic and renal expression …

Perampanel-Induced Cataplexy In A Young Male With Generalized Epilepsy, Kelsey Kenaan, Mohsin Zafar, Ronnie Bond, Barbara L. Gracious

HCA Healthcare Journal of Medicine

Perampanel (Fycompa) is a newer anti-epileptic drug believed to exert its effects in the central nervous system by inhibiting post-synaptic glutamate receptors. However, the precise therapeutic mechanism is unknown. The most common neuropsychiatric side effect is affective dysregulation; there are also reports of psychosis. We describe a 32 year old African American male with recurring generalized tonic-clonic (GTC) seizures, who presented to our hospital with onset of mood lability for several months, after Perampanel was added to his antiepileptic medications. Perampanel administration was temporarily withheld, and subsequently on restarting, noted to be coincident with neuropsychiatric symptomatology, including motor weakness in …

Cyclosporine Shows Benefit As Compared To Methotrexate For Treatment Of Pediatric Atopic Dermatitis Refractory To Topical Medications When Rapidity Of Clinical Response Is Of Key Importance To The Patient, Connor R. Buechler, Steven Daveluy Md

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising El-Khalawany MA, Hassan H, Shaaban D, Ghonaim N, Eassa B. Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt. European Journal of Pediatrics. 2012;172(3):351-356. https://doi.org10.1007/s00431-012-1893-3 for a pediatric patient with severe atopic dermatitis.

Overcoming Barriers For Sirna Therapeutics: From Bench To Bedside, Muhammad Imran Sajid, Muhammad Moazzam, Shun Kato, Kayley Yeseom Cho, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

The RNA interference (RNAi) pathway possesses immense potential in silencing any gene in human cells. Small interfering RNA (siRNA) can efficiently trigger RNAi silencing of specific genes. FDA Approval of siRNA therapeutics in recent years garnered a new hope in siRNA therapeutics. However, their therapeutic use is limited by several challenges. siRNAs, being negatively charged, are membrane-impermeable and highly unstable in the systemic circulation. In this review, we have comprehensively discussed the extracellular barriers, including enzymatic degradation of siRNAs by serum endonucleases and RNAases, rapid renal clearance, membrane impermeability, and activation of the immune system. Besides, we have thoroughly described …

Liposomal Delivery Of Azithromycin Enhances Its Immunotherapeutic Efficacy And Reduces Toxicity In Myocardial Infarction, Ahmed Al-Darraji, Renée R. Donahue, Himi Tripathi, Hsuan Peng, Bryana M. Levitan, Lakshman Chelvarajan, Dalia Haydar, Erhe Gao, David Henson, John C. Gensel, David J. Feola, Vincent J. Venditto, Ahmed K. Abdel-Latif

Gill Heart & Vascular Institute Faculty Publications

A growing body of evidence shows that altering the inflammatory response by alternative macrophage polarization is protective against complications related to acute myocardial infarction (MI). We have previously shown that oral azithromycin (AZM), initiated prior to MI, reduces inflammation and its negative sequelae on the myocardium. Here, we investigated the immunomodulatory role of a liposomal AZM formulation (L-AZM) in a clinically relevant model to enhance its therapeutic potency and avoid off-target effects. L-AZM (40 or 10 mg/kg, IV) was administered immediately post-MI and compared to free AZM (F-AZM). L-AZM reduced cardiac toxicity and associated mortality by 50% in mice. We …

The Acute Effects Of The Atypical Dissociative Hallucinogen Salvinorin A On Functional Connectivity In The Human Brain, Manoj K. Doss, Darrick G. May, Matthew W. Johnson, John M. Clifton, Sidnee L. Hedrick, Thomas E. Prisinzano, Roland R. Griffiths, Frederick S. Barrett

Pharmaceutical Sciences Faculty Publications

Salvinorin A (SA) is a κ-opioid receptor agonist and atypical dissociative hallucinogen found in Salvia divinorum. Despite the resurgence of hallucinogen studies, the effects of κ-opioid agonists on human brain function are not well-understood. This placebo-controlled, within-subject study used functional magnetic resonance imaging for the first time to explore the effects of inhaled SA on strength, variability, and entropy of functional connectivity (static, dynamic, and entropic functional connectivity, respectively, or sFC, dFC, and eFC). SA tended to decrease within-network sFC but increase between-network sFC, with the most prominent effect being attenuation of the default mode network (DMN) during the …

Contraceptive Methods In The United States: The Question Of Abortive Mechanisms, Tara Ferenczy

Senior Honors Theses

This thesis reviews the many methods of contraception available in the United States. Although society’s understanding of women’s health has become a major topic, there is still a significant deficit of information regarding how the accessible methods affect women’s bodies, specifically reproductive tissue. The thesis analyzes numerous contraceptive options focusing specifically on the mechanisms of action to determine whether options have abortifacient properties so that readers may develop educated opinions regarding medical and ethical uses. Information involving strengths and limitations of each technique and the effects on both the female body and the reproductive material assist in understanding the process …

Validation And Application Of A Novel Target-Based Whole-Cell Screen To Identify Antifungal Compounds, Christian Alexander Dejarnette

Theses and Dissertations (ETD)

Traditional approaches to drug discovery are inefficient and have several key limitations that constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically-active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein were constructed, tagged with spectrally distinct fluorescent proteins (FPs), and mixed together. The pooled strains were then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture …

Effects Of Germline And Somatic Events In Candidate Brca-Like Genes On Breast-Tumor Signatures, Weston R. Bodily, Brian H. Shirts, Tom Walsh, Suleyman Gulsuner, Mary-Claire King, Alyssa Parker, Moom Roosan, Stephen R. Piccolo

Pharmacy Faculty Articles and Research

Mutations in BRCA1 and BRCA2 cause deficiencies in homologous recombination repair (HR), resulting in repair of DNA double-strand breaks by the alternative non-homologous end-joining pathway, which is more error prone. HR deficiency of breast tumors is important because it is associated with better responses to platinum salt therapies and PARP inhibitors. Among other consequences of HR deficiency are characteristic somatic-mutation signatures and gene-expression patterns. The term “BRCA-like” (or “BRCAness”) describes tumors that harbor an HR defect but have no detectable germline mutation in BRCA1 or BRCA2. A better understanding of the genes and molecular events associated with tumors being …

Acute And Chronic Dosing Of A High-Affinity Rat/Mouse Chimeric Transferrin Receptor Antibody In Mice, Demi M. Castellanos, Jiahong Sun, Joshua Yang, Weijun Ou, Alexander C. Zambon, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Non-invasive brain delivery of neurotherapeutics is challenging due to the blood-brain barrier. The revived interest in transferrin receptor antibodies (TfRMAbs) as brain drug-delivery vectors has revealed the effect of dosing regimen, valency, and affinity on brain uptake, TfR expression, and Fc-effector function side effects. These studies have primarily used monovalent TfRMAbs with a human constant region following acute intravenous dosing in mice. The effects of a high-affinity bivalent TfRMAb with a murine constant region, without a fusion partner, following extravascular dosing in mice are, however, not well characterized. Here we elucidate the plasma pharmacokinetics and safety of a high-affinity bivalent …

Hypusination Of Eif5a Regulates Cytoplasmic Tdp-43 Aggregation And Accumulation In A Stress-Induced Cellular Model, Shayna Smeltzer, Zainuddin Quadri, Abraian Miller, Frank Zamudio, Jordan Hunter, Nicholas J.F. Stewart, Sheba Saji, Daniel C. Lee, Dale Chaput, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

TAR DNA-binding protein 43 (TDP-43) is a nuclear RNA/DNA binding protein involved in mRNA metabolism. Aberrant mislocalization to the cytoplasm and formation of phosphorylated/aggregated TDP-43 inclusions remains the hallmark pathology in a spectrum of neurodegenerative diseases, including frontotemporal disorders and Alzheimer's disease. Eukaryotic Translation Initiation Factor 5A undergoes a unique post-translation modification of lysine to hypusine (K50), which determines eIF5A binding partners. We used a sodium arsenite-induced cellular stress model to investigate the role of hypusinated eIF5A (eIF5A^HypK50) in governing TDP-43 cytoplasmic mislocalization and accumulation in stress granule. Our proteomics and functional data provide evidence that eIF5A interacts …

Pharmacogenomics Cascade Testing (Phact): A Novel Approach For Preemptive Pharmacogenomics Testing To Optimize Medication Therapy, Don Roosan, Angela Hwang, Moom Roosan

Pharmacy Faculty Articles and Research

The implementation of pharmacogenomics (PGx) has come a long way since the dawn of utilizing pharmacogenomic data in clinical patient care. However, the potential benefits of sharing PGx results have yet to be explored. In this paper, we explore the willingness of patients to share PGx results, as well as the inclusion of family medication history in identifying potential family members for pharmacogenomics cascade testing (PhaCT). The genetic similarities in families allow for identifying potential gene variants prior to official preemptive testing. Once a candidate patient is determined, PhaCT can be initiated. PhaCT recognizes that further cascade testing throughout a …

Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

A cyclic peptide containing one cysteine and five alternating tryptophan and arginine amino acids [(WR)₅C] was synthesized using Fmoc/tBu solid-phase methodology. The ability of the synthesized cyclic peptide to produce gadolinium nanoparticles through an in situ one-pot mixing of an aqueous solution of GdCl₃ with [(WR)₅C] peptide solution was evaluated. Transmission electron microscopy showed the formed peptide-Gd nanoparticles in star-shape morphology with a size of ~250 nm. Flow cytometry investigation showed that the cellular uptake of a cell-impermeable fluorescence-labeled phosphopeptide (F′-GpYEEI, where F′ = fluorescein) was approximately six times higher in the presence of [(WR) …

Cancer-Targeting Immunostimulatory Peptides As An Immunotherapeutic Approach To Cancer, Rachel Montel

Seton Hall University Dissertations and Theses (ETDs)

This dissertation reports the synthesis and biological applications of bifunctional trimeric peptides with B7H6-derived NKp30 binding motifs that serve to activate an immunocytotoxic response in natural killer cells and a GRP78-binding motif that can target tumors that express surface GRP78. In this manner the cancer-targeting immunostimulatory peptides are anticipated to directly bind and activate effector NK92-MI cells while also recognizing and binding to target A549 tumor cells to facilitate NK cell-dependent immunocytotoxicity of the targeted tumors. The NKp30 binding peptide motifs are derived from the tumor associated B7H6 antigen that is often downregulated or shed from the surface of tumors …

Urinary Bile Acid Indices As Diagnostic And Prognosic Biomarkers For Liver Diseases, Jawaher Alamoudi

Theses & Dissertations

Hepatobiliary diseases result in the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues which may contribute to an unfavorable prognosis. We compared the urinary BA profile between 300 patients with hepatobiliary diseases vs. 103 healthy controls. Also, we investigated the use of the urinary BA profile to develop survival models to predict the prognosis of hepatobiliary diseases. The urinary BA profile, a set of non-BA parameters, and the adverse events of liver transplant and/or death were monitored in patients with cholestatic liver diseases for up to 7 years. The BA profile was characterized by calculating …

Crnas And Sugammadex Use: A Qualitative Analysis, Natalia Izquierdo Bsn, Rn, Emily Mancewicz Bsn, Rn

Grace Peterson Nursing Research Colloquium

Background: The availability of Sugammadex has increased options for Certified Registered Nurse Anesthetists’ (CRNAs) and their choice of neuromuscular reversal agents, however administration is impacted by a variety of provider and institutional factors.

Objectives: The purpose of this study was to examine and describe the personal and institutional factors impacting the use of Sugammadex in Illinois by CRNAs.

Method: A qualitative study design using an open-ended survey yielded 209 responses. The three main themes that emerged were 1) Why CRNAs choose to use or avoid Sugammadex 2) How CRNAs dose Sugammadex and 3) Practice variations existing within the clinical setting. …

Cytokine Storm In Covid-19: An Overview, Mechanism, Treatment Strategies, And Stem Cell Therapy Perspective, Nuriza Ulul Azmi, Meidi Utami Puteri, Donny Lukmanto

Pharmaceutical Sciences and Research

Coronavirus disease 2019 (COVID-19) is the disease caused by the highly transmittable novel coronavirus (SARS-CoV-2) infections. The disease was found at the end of December 2019, in Wuhan, China, and quickly spread worldwide with a higher mortality rate compared to the previous coronavirus disease. Cytokine plays an important role in the inflammatory response against coronavirus infection. However, in severely ill patients with COVID-19, an excessive amount of cytokine serum level (cytokine storm) has been associated with the aggravation of coronavirus disease leading to acute respiratory distress syndrome (ARDS). Thus, the management of the cytokine storm could be the key to …

Prion Protein Lowering Is A Disease-Modifying Therapy Across Prion Disease Stages, Strains And Endpoints, Eric Vallabh Minikel, Hien T. Zhao, Jason Le, Jill O'Moore, Rose Pitstick, Samantha Graffam, George A. Carlson, Michael P. Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

Lowering of prion protein (PrP) expression in the brain is a genetically validated therapeutic hypothesis in prion disease. We recently showed that antisense oligonucleotide (ASO)-mediated PrP suppression extends survival and delays disease onset in intracerebrally prion-infected mice in both prophylactic and delayed dosing paradigms. Here, we examine the efficacy of this therapeutic approach across diverse paradigms, varying the dose and dosing regimen, prion strain, treatment timepoint, and examining symptomatic, survival, and biomarker readouts. We recapitulate our previous findings with additional PrP-targeting ASOs, and demonstrate therapeutic benefit against four additional prion strains. We demonstrate that

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 …

Foundational Research And Nih Funding Enabling Emergency Use Authorization Of Remdesivir For Covid-19, Ekaterina Galkina Cleary, Matthew J. Jackson, Zoë Folchman-Wagner, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Emergency Use Authorization for remdesivir months after discovery of COVID-19 is unprecedented. Typically, decades of research and public-sector funding are required to establish the mature body of foundational research requisite for efficient, targeted drug discovery and development. This work quantifies the body of research related to remdesivir’s biological target, RNA-dependent RNA polymerase (RdRp), or parent chemical structure, nucleoside analogs (NcAn), through 2019, as well as NIH funding for this research 2000–2019. There were 6,567 RdRp-related publications in PubMed, including 1,263 with NIH support, and 11,073 NcAn-related publications, including 2,319 with NIH support. NIH support for RdRp research comprised 2,203 Project …

Are We Missing The Target? Are We Aiming Too Low? What Are The Aerobic Exercise Prescriptions And Their Effects On Markers Of Cardiovascular Health And Systemic Inflammation In Patients With Knee Osteoarthritis? A Systematic Review And Meta-Analysis, Jenna M. Schulz, Trevor B. Birmingham, Hayden F. Atkinson, Emilie Woehrle, Codie A. Primeau, Michael J. Lukacs, Baraa K. Al-Khazraji, Michaela C.M. Khan, Bryn O. Zomar, Robert J. Petrella, Frank Beier, C. Thomas Appleton, J. Kevin Shoemaker, Dianne M. Bryant

Physiology and Pharmacology Publications

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Objectives We systemically reviewed published studies that evaluated aerobic exercise interventions in patients with knee osteoarthritis (OA) to: (1) report the frequency, intensity, type and time (FITT) of exercise prescriptions and (2) quantify the changes in markers of cardiovascular health and systemic inflammation. Data sources PubMed, CINAHL, Scopus; inception to January 2019. Eligibility criteria Randomised clinical trials (RCT), cohort studies, case series. Design We summarised exercise prescriptions for all studies and calculated effect sizes with 95% CIs for between-group (RCTs that compared exercise and …

Role Of Neuronal Nitric Oxide Synthase On Cardiovascular Functions In Physiological And Pathophysiological States, Ahmmed Ally, Isabella Powell, Minora M. Ally, Kevin Chaitoff, Surya M. Nauli

Pharmacy Faculty Articles and Research

This review describes and summarizes the role of neuronal nitric oxide synthase (nNOS) on the central nervous system, particularly on brain regions such as the ventrolateral medulla (VLM) and the periaqueductal gray matter (PAG), and on blood vessels and the heart that are involved in the regulation and control of the cardiovascular system (CVS). Furthermore, we shall also review the functional aspects of nNOS during several physiological, pathophysiological, and clinical conditions such as exercise, pain, cerebral vascular accidents or stroke and hypertension. For example, during stroke, a cascade of molecular, neurochemical, and cellular changes occur that affect the nervous system …

Veterinarians’ Attitudes And Practices Regarding Opioid-Related Vet Shopping Practices In Tri-State Appalachian Counties: An Exploratory Study, Falguni C Patel, Jeffrey A Raines, Richard W Kim, Karen Gruszynski, Robert E Davis, Manoj Sharma, Gilbert Patterson, Jason W Johnson, Vinayak K Nahar

Faculty, Staff and Students Publications

BACKGROUND: The opioid crisis continues to grow in the United States with 46,700 drug overdose deaths due to opioids in 2017 alone. Vet shopping, the practice of soliciting veterinarians for prescription medications, has been receiving national media attention in recent years. A 2014 review of Prescription Monitoring Drug Programs found less than 10 veterinary shoppers nationwide. Still much is unknown about the role of vet shopping and the opioid crisis. This study sought to understand the practice of vet shopping through the eyes of veterinarians practicing in Appalachian counties within the states of Kentucky, Tennessee, and Virginia, United States.

RESULTS: …

Targeting The Transferrin Receptor To Develop Erythropoietin For Alzheimer’S Disease, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

"Alzheimer’s disease (AD) is the sixth leading cause of death in the United States with approximately 5.8 million Americans currently living with AD. Due to the lack of a disease modifying treatment for AD and the aging baby boomer generation, this number is projected to grow to 13.8 million by 2050 (Gaugler et al., 2019). Amyloid-beta (Aβ) plaque accumulation, one of the major pathological hallmarks of AD, can begin > 20 years before clinical symptoms of AD. By the time AD is clinically diagnosed, neuronal loss and neuropathological lesions (Aβ plaques and tau tangles) have already occurred in many brain regions …

Comparative Molecular Transporter Properties Of Cyclic Peptides Containing Tryptophan And Arginine Residues Formed Through Disulfide Cyclization, Eman H. M. Mohammed, Dindyal Mandal, Saghar Mozaffari, Magdy Abdel-Hamied Zahran, Amany Mostafa Osman, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously reported cyclic cell-penetrating peptides [WR]₅ and [WR]₄ as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated their cytotoxicity as well as uptake behavior against different cancer cell lines. Thus, cyclic [C(WR)_xC] and linear counterparts (C(WR)_xC), where x = 4–5, were synthesized using Fmoc/tBu solid-phase peptide synthesis, purified, and characterized. The compounds did not show any significant cytotoxicity (at 25 µM) against ovarian (SK-OV-3), leukemia (CCRF-CEM), gastric adenocarcinoma (CRL-1739), breast …

Reduced Expression Of The Pp2a Methylesterase, Pme-1, Or The Pp2a Methyltransferase, Lcmt-1, Alters Sensitivity To Beta-Amyloid-Induced Cognitive And Electrophysiological Impairments In Mice, Agnieszka Staniszewski, Hong Zhang, Kesava Asam, Rose Pitstick, Michael P. Kavanaugh, Ottavio Arancio, Russell E. Nicholls

Biomedical and Pharmaceutical Sciences Faculty Publications

Beta-amyloid (Ab) is thought to play a critical role in Alzheimer’s disease (AD), and application of soluble oligomeric forms of Ab produces AD-like impairments in cognition and synaptic plasticity in experimental systems. We found previously that transgenic overexpression of the PP2A methylesterase, PME-1, or the PP2A methyltransferase, LCMT-1, altered the sensitivity of mice to Ab-induced impairments, suggesting that PME-1 inhibition may be an effective approach for preventing or treating these impairments. To explore this possibility, we examined the behavioral and electrophysiological effects of acutely applied synthetic Ab oligomers in male and female mice heterozygous for either a PME-1 KO or …

Olive Oil Diet In Mild Pre-Gestational Diabetes Impacts Offspring Β-Cell Development., Bushra Taqui, Farsad Asadi, Evangelina Capobianco, Daniel Barry Hardy, Alicia Jawerbaum, Edith Juliana Arany

Physiology and Pharmacology Publications

Maternal diabetes impairs fetal development and increases the risk of metabolic diseases in the offspring. Previously, we showed maternal dietary supplementation with 6% of olive oil prevents diabetes-induced embryo and fetal defects, in part, through the activation of peroxisome proliferator-activated receptors (PPARs). In this study we examined the effects of this diet on neonatal and adult pancreatic development in both male and female offspring. A mild diabetic model was developed by injecting neonatal rats with streptozotocin (90 mg/kg). During pregnancy these dams were fed a chow diet supplemented or not with 6% olive oil. Dual immunohistochemistry was performed to detect …

Inflammation Profiling Of Critically Ill Coronavirus Disease 2019 Patients., Douglas D Fraser, Gediminas Cepinskas, Marat Slessarev, Claudio Martin, Mark Daley, Michael R Miller, David B O'Gorman, Sean E Gill, Eric K Patterson, Claudia C Dos Santos

Physiology and Pharmacology Publications

Objectives: Coronavirus disease 2019 is caused by severe acute respiratory syndrome-coronavirus-2 infection to which there is no community immunity. Patients admitted to ICUs have high mortality, with only supportive therapies available. Our aim was to profile plasma inflammatory analytes to help understand the host response to coronavirus disease 2019.

Design: Daily blood inflammation profiling with immunoassays.

Setting: Tertiary care ICU and academic laboratory.

Subjects: All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome-coronavirus-2, using standardized hospital screening methodologies, had daily blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus …