Chemicals and Drugs Commons^™

Hla Pharmacogenetic Markers Of Drug Hypersensitivity From The Perspective Of The Populations Of The Greater Middle East, Hend Chaker Masmoudi, Nariman Afify, Halima Alnaqbi, Zainab Alhalwachi, Guan Kwang Tay, Habiba Alsafar

Research outputs 2022 to 2026

Specific HLA associations with drug hypersensitivity may vary between geographic regions and ethnic groups. There are little to no data related to HLA-drug hypersensitivity on populations who reside in the Greater Middle East (GME), a vast region spanning from Morocco in the west to Pakistan in the east. In this review, the authors intended to summarize the significant HLA alleles associated with hypersensitive drug reactions induced by different drugs, as have been found in different populations, and to summarize the prevalence of these alleles in the specific and diverse populations of the GME. For example, HLA-B * 57:01 allele prevalence, …

Development Of A Decellularized Hydrogel Composite And Its Application In A Novel Model Of Disc-Associated Low Back Pain In Female Sprague Dawley Rats, David Lillyman

Biological Systems Engineering--Dissertations, Theses, and Student Research

Chronic low back pain is a global socioeconomic crisis compounded by an absence of reliable, curative treatments. The predominant pathology associated with chronic low back pain is degeneration of intervertebral discs in the lumbar spine. During degeneration, nerves can sprout into the intervertebral disc tissue and be chronically subjected to inflammatory and mechanical stimuli, resulting in pain. Pain arising from the intervertebral disc, or disc-associated pain, is a complex, multi-faceted disorder which necessitates valid animal models to screen therapeutics and study pathomechanisms of pain.

While many research teams have created animal models of disc degeneration, the translation of these platforms …

Treatment Of Tardive Dyskinesia With High Dose Vitamin B6 Associated With Depression, Marjorie Mccoy, Adam Schindzielorz, Suzanne Holroyd

Marshall Journal of Medicine

Tardive dyskinesia (TD) is a movement disorder associated with dopamine receptor blocking medications. Recommended treatments for TD include discontinuing the causative agent, adding vesicular monoamine transporter 2 (VMAT2) inhibitors, or adding vitamin B6. We present a 66-year-old Caucasian male with bipolar I disorder who developed TD while on lithium and quetiapine having been euthymic on this regimen for three years. He was initially treated with 1200 mg B6 daily. This failed to improve his TD and was associated with a depressive episode. He switched to valbenazine 40 mg daily which improved his TD and concurrently his mood, but months later …

Synthesis Of Triaminopyrimidine Derivatives For Inhibition Of Inflammatory Caspases, Marianna C. Haddad, Caitlin Karver

DePaul Discoveries

Caspases are cysteine-dependent aspartic proteases whose functions are connected to different mechanisms of cell death and inflammation. As caspase-1 plays a significant role in the immune response, its activity has been of interest as a target for inhibitor development as its inhibition will reduce the levels of pro-inflammatory cytokines in inflammatory diseases, thus minimizing the symptoms that arise and serving as a possible therapeutic approach. Prior work discovered a family of potent inhibitors of caspase-1 with a common triaminopyrimidine scaffold. To further explore structure-activity relationship profiles of potential inhibitors of caspase-1, two different syntheses were attempted to create two new …

Electrochemical Deposition Of Calcium Phosphate-Based Coatings Onto Porous Ti Using Organic Phosphorus Sources, Clement Lee

Electronic Thesis and Dissertation Repository

The study and commercialization of calcium phosphate (Ca-P) coatings has occurred for several decades. However, this has typically involved the use of hydroxyapatite. This thesis presents the synthesis of different Ca-P-based coatings that has not been studied. Anodic oxidation was employed to create a porous Ti substrate, while pulsed electrochemical deposition was used to deposit the coating onto the Ti. The first coating synthesized was a calcium phosphoserine (Ca-pSer) complex, which contained two different morphologies: a flower-like structure at low deposition time and a unique cubic morphology at higher deposition times. Next, an amorphous calcium phosphate coating was synthesized and …

In-Silico Analysis Of Interacting Pathways Through Kim-1 Protein Interaction In Diabetic Nephropathy, Fatima Abid, Z Rubab, Syeda Sadia Fatima, A Qureshi, Arfa Azhar, A Jafri

Department of Biological & Biomedical Sciences

Background: Human Kidney Injury Molecule-1, also known as HAVCR-1 (Hepatitis A virus cellular receptor 1), belongs to the cell-surface protein of immunoglobulin superfamily involved in the phagocytosis by acting as scavenger receptor epithelial cells. The study focused on pinpointing the mechanisms and genes that interact with KIM-1.
Methods: This in-silico study was done from March 2019 to December 2019. The Enrichment and protein-protein interaction (PPI) network carefully choose proteins. In addition, the diagramed gene data sets were accomplished using FunRich version 3.1.3. It was done to unveil the proteins that may affect the regulation of HAVCR1 or may be regulated …

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang

Pharmacy Faculty Articles and Research

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several …

Integrating Conformational Dynamics And Perturbation-Based Network Modeling For Mutational Profiling Of Binding And Allostery In The Sars-Cov-2 Spike Variant Complexes With Antibodies: Balancing Local And Global Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

n this study, we combined all-atom MD simulations, the ensemble-based mutational scanning of protein stability and binding, and perturbation-based network profiling of allosteric interactions in the SARS-CoV-2 spike complexes with a panel of cross-reactive and ultra-potent single antibodies (B1-182.1 and A23-58.1) as well as antibody combinations (A19-61.1/B1-182.1 and A19-46.1/B1-182.1). Using this approach, we quantify the local and global effects of mutations in the complexes, identify protein stability centers, characterize binding energy hotspots, and predict the allosteric control points of long-range interactions and communications. Conformational dynamics and distance fluctuation analysis revealed the antibody-specific signatures of protein stability and flexibility of the …

A Changing Epidemic And The Rise Of Opioid-Stimulant Co-Use, Saeed Ahmed, Zouina Sarfraz, Azza Sarfraz

Department of Paediatrics and Child Health

No abstract provided.

Emicizumab-Kxwh: A Critical Review, Kiera O'Leary

International Undergraduate Journal of Health Sciences

The first descriptions of haemophilia A were reported in the second century AD, with the first modern description by John Conrad Otto in 1803. Historically, the natural history of haemophilia A was associated with very high rates morbidity and mortality, often following trivial accidents. Although treatment options for haemophilia A have been revolutionised in recent decades, haemophilia A remains a hereditary disease of concern and factor replacement products remain the mainstay of treatment.

As such, patients with haemophilia can carry huge burdens, particularly when a complication such as a FVIII inhibitor is present. A recently approved novel therapeutic, Emicizumab-kxwh, has …

Multidrug Resistance In Cancer: Understanding Molecular Mechanisms, Immunoprevention And Therapeutic Approaches, Talha Bin Emran, Asif Shahriar, Aar Rafi Mahmud, Tanjilur Rahman, Mehedy Hasan Abir, Mohd Faijanur-Rob Siddiquee, Hossain Ahmed, Nova Rahman, Firzan Nainu, Elly Wahyudin

School of Medicine Publications and Presentations

Cancer is one of the leading causes of death worldwide. Several treatments are available for cancer treatment, but many treatment methods are ineffective against multidrug-resistant cancer. Multidrug resistance (MDR) represents a major obstacle to effective therapeutic interventions against cancer. This review describes the known MDR mechanisms in cancer cells and discusses ongoing laboratory approaches and novel therapeutic strategies that aim to inhibit, circumvent, or reverse MDR development in various cancer types. In this review, we discuss both intrinsic and acquired drug resistance, in addition to highlighting hypoxia- and autophagy-mediated drug resistance mechanisms. Several factors, including individual genetic differences, such as …

17Β-Estradiol Treatment Improves Acetylcholine-Induced Relaxation Of Mesenteric Arteries In Ovariectomized Uc Davis Type 2 Diabetes Mellitus Rats In Prediabetic State, Md Rahatullah Razan, Farjana Akther, Rifat Ara Islam, James L. Graham, Kimber L. Stanhope, Peter J. Havel, Roshanak Rahimian

School of Pharmacy Faculty Articles

We recently reported sex differences in mesenteric arterial function of the UC Davis type-2 diabetes mellitus (UCD-T2DM) rats as early as the prediabetic state. We reported that mesenteric arteries (MA) from prediabetic male rats exhibited a greater impairment compared to that in prediabetic females. However, when females became diabetic, they exhibited a greater vascular dysfunction than males. Thus, the aim of this study was to investigate whether the female sex hormone, estrogen preserves mesenteric arterial vasorelaxation in UCD-T2DM female rats at an early prediabetic state. Age-matched female Sprague Dawley and prediabetic (PD) UCD-T2DM rats were ovariectomized (OVX) and subcutaneously implanted …

Biowill - Characterising Willow Bark Bio-Actives For Skin Therapies, Arnold Marisa

ORBioM (Open Research BioSciences Meeting)

Willow bark is considered as a disposable by-product when processing willow for biomass. Willow (Salix) is known to contain high value bioactive compounds which include salicin and its derivatives, and other phytochemicals of interest such as polyphenols and flavonoids. The plant is historically known as the primary source of salicylates to which the well-known drug aspirin is derived from. The work forms part of the Interreg project BioWILL, which is focused on integrated “Zero Waste” biorefinery utilising all fractions of willow feedstock for the production of biochemicals and renewable energy. This project aims to investigate the crude and …

Thromboelastography Profiles Of Hemophilia A Patients On Emicizumab, Daniel J. Vanzweden, Meera Chitlur, Charity J. Stadler

Medical Student Research Symposium

Emicizumab is a new monoclonal antibody developed to dtreat people with Hemophilia A, especially those with antibodies. However, breakthrough bleeding can still occur in patients taking Emicizumab. TEG is a global coagulation assay which measures coagulability through viscosity. This study describes the use of tissue factor activated TEG in measuring bleeding profiles in patients taking Emicizumab. The goal of this prospective study is to determine if TEG can be used, which variables of TEG might be useful, and how much more useful it is than the current standard, aPtt. Findings include a 25% increased R time and 24% increased K …

Sex Differences In Locomotor Activity And Behavioral Sensitization In Rats Administered Fentanyl, Jessica J. Lee, Nareen Sadik, Cameron Davidson Phd, Majd Yahya, Josie Zdun, Shane Perrine Phd

Medical Student Research Symposium

Opioid overdoses have continued to increase, and women have experienced a greater rate of increase than males. Preclinical studies demonstrate marked sex differences in addiction-related behaviors, with females being more vulnerable due to a potential role of estradiol. We sought to understand how the estrous cycle, as a proxy measure of estradiol, influences sex differences in the sensitizing effects of fentanyl. In this ongoing study, we used male and female rats to investigate potential sex effects of fentanyl (20µg/kg subcutaneously) administration for 14 days and a forced abstinence period of 13 days on behavioral sensitization via locomotor activity (LMA) following …

Developing An Accurate Empirical Correlation For Predicting Anti-Cancer Drugs’ Dissolution In Supercritical Carbon Dioxide, Fardad Faress, Amin Yari, Fereshteh Rajabi Kouchi, Ava Safari Nezhad, Alireza Hadizadeh, Leili Sharif Bakhtiar, Yousef Naserzadeh, Niloufar Mahmoudi

International Business and Entrepreneurship Faculty Publications and Presentations

This study introduces a universal correlation based on the modified version of the Arrhenius equation to estimate the solubility of anti-cancer drugs in supercritical carbon dioxide (CO2). A combination of an Arrhenius-shape term and a departure function was proposed to estimate the solubility of anti-cancer drugs in supercritical CO2. This modified Arrhenius correlation predicts the solubility of anti-cancer drugs in supercritical CO2 from pressure, temperature, and carbon dioxide density. The pre-exponential of the Arrhenius linearly relates to the temperature and carbon dioxide density, and its exponential term is an inverse function of pressure. Moreover, the departure function linearly correlates with …

Synthesis Of Curcumin Derivatives: Increasing Compound Stability, Chloe Wilke

Undergraduate Research Symposium

Curcumin (C₂₁H₂₀O₆), the main active component in the spice Turmeric, has many recognized health benefits ranging from anti-inflammatory agents to the suppression of the proliferation of tumors. Curcumin has been used worldwide as an antiseptic and treatment for inflammatory conditions, arthritis, and sepsis. This water-insoluble molecule is unstable and degrades quickly upon entering the body. In order to preserve the beneficial structure of curcumin before it is broken down by the digestive system, carbohydrates are attached to alter the compound, increasing polarity and solubility. This topic was researched by analyzing multiple journal articles and …

Benzofuran Derivatives Substitute For The Discriminative Stimulus Effects Of 3,4methylenedioxymethamphetamine (Mdma) In Male Sprague-Dawley Rats, Candace Johnson

Masters Theses

4-Methylenedioxymethamphetamine (MDMA) is currently under evaluation in phase III clinical trials as medication-assisted therapy for post-traumatic stress disorder (PTSD) and is expected to be approved by the FDA for clinical use in the near future. MDMA is also a popular abused substance with risks for cardiovascular toxicity and neurotoxicity, particularly when misused at higher doses. Characterization of the behavioral and neurochemical effects of novel psychoactive substances is an essential step in the development of safer alternative therapeutic agents. Drug discrimination is a preclinical behavioral assay with pharmacological specificity for characterizing in vivo drug actions in the central nervous system. This …

Expression And Purification Of The Bacterial Protein Curli Csga And Its Cross-Interactions With Amyloid-B, Leah Grace Cantrell

Honors Theses

One of the main causes of neurodegenerative diseases is aggregation of amyloid proteins that are toxic to the neurons. Proteins like amyloid-β (Aβ) and α-syneuclein (α-syn) form hallmark aggregate lesions that contribute to pathological processes in the brain in Alzheimer and Parkinson’s patients, respectively. Recent ground-breaking studies have suggested a link between the microbiota of the gut and neurodegenerative diseases, called the “gut-brain axis.” It has been long known that the protein, CsgA found in many enteric bacteria, forms amyloid fibers of its own called Curli. Curli fibrils are a structural component of bacterial colonies and maintain the integrity of …

Data-Driven Analysis Of Drug And Substance Abuse Rates Across The Varying Regions In The United States Of America, Reem Saleh

University Honors Theses

Drugs and substance abuse is one of the leading causes of death for adolescents in the United States. The consequences of using these drugs are profound and can cause both damage to one's physical and psychological health. The rates of drug abuse in the United States continue to increase over the years. This paper analyzes the trends in rates of drug abuse in the four regions in the United States. It looks at the rates in cocaine, cigarettes, marijuana, and tobacco. A preliminary analysis was done to look at the trend in rates followed by an ARIMA time series model …