Chemicals and Drugs Commons^™

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

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 …

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 …

Crel And Wnt5a/Frizzled 5 Receptor-Mediated Inflammatory Regulation Reveal Novel Neuroprotectin D1 Targets For Neuroprotection, Jorgelina M. Calandria, Khanh V. Do, Sayantani Kala-Bhattacharjee, Andre Obenaus, Ludmila Belayev, Nicolas G. Bazan

School of Medicine Faculty Publications

Abstract: Wnt5a triggers inflammatory responses and damage via NFkB/p65 in retinal pigment epithelial (RPE) cells undergoing uncompensated oxidative stress (UOS) and in experimental ischemic stroke. We found that Wnt5a-Clathrin-mediated uptake leads to NFkB/p65 activation and that Wnt5a is secreted in an exosome-independent fashion. We uncovered that docosahexaenoic acid (DHA) and its derivative, Neuroprotectin D1 (NPD1), upregulate c-Rel expression that, as a result, blunts Wnt5a abundance by competing with NFkB/p65 on the Wnt5a promoter A. Wnt5a increases in ischemic stroke penumbra and blood, while DHA reduces Wnt5a abundance with concomitant neuroprotection. Peptide inhibitor of Wnt5a binding, Box5, is also neuroprotective. DHA-decreased …

Migratory Dermatographic Urticaria Following Covid-19 Vaccine Booster In Young Adult Male, Richard A. Maiella, Kelly Staples, Ashok Veldanda

Rowan-Virtua Research Day

With the recent approval of booster vaccinations in the United States for adults who already received their primary vaccinations, millions of adults have been administered the Pfizer-BioNTech or Moderna booster vaccines.

Adverse events related to these vaccines continue to be reported and are majority self-limited. In this case report, we present a young male who acquired chronic, migratory dermatographic urticaria two weeks after administration of the Moderna mRNA-1273 COVID-19 vaccine booster.

Stroke In Hfref Without Atrial Fibrillation And Concurrent Protein S Deficiency: What Is The Best Treatment?, Rohan Umrani, Trinava Roy, Bhavana Kadiyala, Yvette Wang

Rowan-Virtua Research Day

Hypercoagulable disorders are often the culprit for repeated strokes in young patients, with or without other comorbidities

Medications typically used for stroke prophylaxis:

• Warfarin
• Aspirin
• Direct Oral Anticoagulants (DOACs)

Warfarin is the preferred method of anticoagulation for stroke prophylaxis in patients with hypercoagulable disorders

A deficiency of protein S increases the risk of pro coagulation due to a relative deficiency of anticoagulants.

Patients with protein S deficiency tend to have recurrent venous thromboses and pulmonary emboli

Treating Trichotillomania With Olanzapine, Christopher Lee

Rowan-Virtua Research Day

Trichotillomania (TTM) is characterized by repetitive pulling of one’s hair leading to hair loss and problems in social, occupational, or other important areas of functioning. Often individuals with TTM try to decrease or stop hair pulling, however are often unsuccessful without treatment. Community prevalence studies suggest that TTM is a common disorder with point prevalence estimate of 0.5% to 2.0% and with significant psychological comorbidity. Of note, people with TTM are often embarrassed about their condition, so epidemiology data may be underestimated compared to the true prevalence of this condition. The female to male ratio for this condition is 4:1. …

Case Report: Covid Arm (Covid Vaccine Arm), Joseph Pagano, James Espinosa, Alan Lucerna, Henry Schuitema

Rowan-Virtua Research Day

We report the case of a 38-year-old male physician who was vaccinated with the Pfizer vaccine. He experienced arm pain and swelling on the vaccinated arm as well as systemic symptoms, including fever, chills, headache and weakness. The systemic symptoms improved after the use of oral prednisone. A review of the literature on the COVID vaccine is presented.

Case Report: Octreotide Associated Hyperkalemia, Darren Finn, Eric Maddock, James Espinosa, Andrew Caravello, Alan Lucerna, Henry Schuitema

Rowan-Virtua Research Day

78-year-old female with past medical history of acromegaly status post pituitary adenoma status post resection presents to the emergency department with abdominal pain. ED workup was not significant for any acute intra-abdominal abnormalities; however, incidental finding of hyperkalemia was pertinent to the visit. Patient was treated in the ED for her condition but her potassium levels remained elevated despite repeated saline infusions. Patient was ultimately admitted to the hospital where it was discovered that she had recently been switched from octreotide injections to an oral somatostatin analogue Mycapssa. We believe that this patient’s hyperkalemia was caused by octreotide-induced insulin suppression …

Digoxin Toxicity And Acute Renal Failure In A 75 Year-Old Female, Daniel Zaayenga, Andrew Caravello, Nicholas Tomasello

Rowan-Virtua Research Day

Digoxin toxicity can present with varying manifestations. While pathognomonic symptoms such as xanthopsia (object appearing yellow) are a board favorite it is not a required finding and is in fact not seen with most patients. Rather digoxin toxicity presents with more non-specific symptoms such as GI distress (anorexia, N/V) neurological distress (lethargy, fatigue, delirium, confusion, disorientation, weakness. EKG findings are varied and include premature ventricular contractions, bradycardia, atrial tachyarrhythmias with AV block, ventricular bigeminy, junctional rhythms, various degrees of AV nodal blockade, ventricular tachycardia, and ventricular fibrillation. Although rarely seen, digoxin is one of the only causes of bidirectional ventricular …

Seizure To Drug Induced Schizophrenia: A Rare Case Of Keppra-Induced Psychosis, Shadi Shams, Riddhima Issar, Nardin El-Shammaa, Munaza Khan

Rowan-Virtua Research Day

Levetiracetam is a broad-spectrum antiseizure medication and is approved as adjunctive therapy to treat focal-onset seizures in children and adults with epilepsy. Levetiracetam has a wide margin of safety and patient-friendly pharmacokinetics that distinguish it from other currently available antiepileptic drugs.

Most common side effects are fatigue, somnolence, dizziness, and upper respiratory infection. Neuropsychiatric symptoms are reported. Psychotic symptoms, paranoid ideation, hallucinations, and behavioral problems may occur in adult and pediatric patients. Among all adverse effects, the rate of psychosis is very low and ranges from less than 1% to 1.4%. A retrospective study showed that this rate is higher …

Improvement Of Memory Loss Through Dietary Intervention In The Assisted Living And Rehabilitative Settings, Alexander Swartz, Martin Forsberg

Rowan-Virtua Research Day

• The ketogenic diet is a popular, controversial diet that fuels the brain through beta-oxidation of fatty acids and production of ketone bodies, the most populous of which is betahydroxybutyrate (BHB).

• The ketogenic diet consists of 70-80% fats, 20-25% protein, and 5-10% carbohydrates.

• Medically, the ketogenic diet is utilized in patients with epilepsy and recommended by some physicians to improve general health through weight loss and insulin sensitivity.

• Key factors of neurodegeneration include glucose hypometabolism, oxidative damage, and neuroinflammation.

• Studies have shown that with ingestion of exogenous ketones alone, or endogenous ketonemia through a ketogenic diet, there is: …

Riluzole For Pediatric Patients With Treatment-Refractory Obsessive-Compulsive Disorder, Maheen Mohammad, Stuti Parikh

Rowan-Virtua Research Day

Obsessive-compulsive disorder (OCD) occurs in about 1-3% of the pediatric population, but many do not respond to standard therapies. Riluzole, a glutamate antagonist, has shown to be an effective treatment for refractory OCD in adults, however few trials have been conducted to show the effectiveness of Riluzole in children to treat refractory OCD. The study investigates the potential use of riluzole in children to treat refractory OCD.

Effect Of Calcium Chloride And Isoflurane On Force Frequency Relationship In Canines, Harrison Patrizio, Lawrence Mulligan

Rowan-Virtua Research Day

Proper calcium cycling is critical for a optimally functioning heart.

Improper calcium cycling in humans can contribute to heart failure.

Human calcium cycling is difficult to study due to the risks of damaging the patient’s cardiac tissue.

Risk of further damaging cardiac tissue is substantially increased in a heart failure patient.

Past studies focus on studying the effects of changing calcium cycling in lab rats.

Current research shows limited alternative methods in studying relationships between calcium cycling and FFR in larger mammals.

This project analyzes data to determine the response of the canine force frequency relationship to calcium chloride and …

The Role Of Physiologic Vision Deficits In Elderly Self Dispensing Medication Errors, Harrison Patrizio

Rowan-Virtua Research Day

Elderly populations are more prone to self-dispensing medication errors. Although some of these errors can be attributed to a patient’s disease, many errors are preventable with behavioral modification. As we age, the lens of the eye becomes yellow. This tints all light that passes through it causing deficits in color distinguishability.(Andreasen, 1980) Additionally, the lens of the eye hardens over time. This results in presbyopia, an inability to focus close objects.(Wolffsohn, 2018) These changes can cause elderly patients to misread labels or dispensed incorrect medication due to color shade similarities.(Cardarelli, 2011) Although these visual changes are well documented, current research …

Case Study Of Metformin-Induced Lactic Acidosis, Kajel Patel, Kishan B. Patel

Rowan-Virtua Research Day

Metformin induced lactic acidosis is when high levels of metformin cause dangerously high levels of lactic acid. Here is a case report of a 72-year-old female who came in for nausea, vomiting, and diarrhea found to have a high suspicion for metformin induced lactic acidosis. She stabilized in the emergency department, nephrology and ICU was contacted, and she went for emergent dialysis. For many patients the prognosis of metformin induced lactic acidosis is poor. This patient was made comfort care by her family.

Long-Term Lithium Use In The Younger Population: Do The Benefits Outweigh The Risks? - A Case Report, Seema Shekar, Alexander Garcia, Rachel Shmuts

Rowan-Virtua Research Day

For decades lithium has been the mainstay treatment for bipolar disorder. While its side effect profile is extensive and varied its most notable adverse effect, and one most feared by treating clinicians, is nephrotoxicity/ end-stage renal disease (ESRD). While the link between long-term lithium use and ESRD has been accepted by the medical community at large for many years, more recent scientific studies call the association into question. In fact, newer studies on the association between Li use and ESRD have shown a negative/inconclusive correlation. Despite this controversy the consensus still remains that ESRD secondary to long-term Li use is …

Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong

Pharmaceutical Sciences (PhD) Dissertations

Human cutaneous melanoma is the most aggressive form of skin cancer and the incidence rates have continued to increase over the years. Neuronal nitric oxide synthase (nNOS) produces nitric oxide (NO) has been found to be overexpressed in human melanoma and the expression of nNOS is induced by interferon-gamma (IFN-γ). In our studies, nNOS has been implicated in IFN-γ-stimulated melanoma progression and the inhibition of nNOS using novel inhibitors effectively inhibited IFN-γ-stimulated tumor growth in a xenograft mouse model. Programmed death-ligand 1 (PD-L1) is overexpressed in melanoma and plays an important role in suppressing the immune system ^12-14. Our …

Effects Of Increased Levels Of Relaxin Hormone In Women During Pregnancy In Relation To Spondylolisthesis: A Literature Review, Joselin R. Guerrero Rapalo

Honors Theses

No abstract provided.

Applying Mci-062, A Novel Pan-Ras Inhibitor, To Treat Kras-Mutant Lung Cancer, Richard Fu

Honors Theses

RAS is a prevalent oncogene that is mutated in 27% of human cancers. Gain-of-function RAS mutations activate multiple downstream pathways, including the RAS-RAF-MEK-ERK and PI3K/AKT/mTOR pathways, which are critical in tumorigenesis and cancer cell proliferation. RAS proteins such as KRAS, a member of the RAS protein family, and their downstream effectors are attractive targets for cancer therapy since their mutations act as frequent drivers in lung, colorectal, and pancreatic cancers. However, RAS proteins have relatively smooth surfaces that lack traditional binding pockets, making inhibitors specific to RAS difficult to create. Recently, a novel small molecule pan-RAS inhibitor named MCI-062 was …

Hdac6 Inhibition Reverses Long-Term Doxorubicin-Induced Cognitive Dysfunction By Restoring Microglia Homeostasis, Blake Mcalpin

Dissertations and Theses (Open Access)

One in 8 women in the US will be diagnosed with breast cancer. Currently, doxorubicin is one of the most effective chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by deficits in working memory, processing speed, and executive functioning. Currently, no interventions for CICD have been approved by the US Food and Drug Administration. I show here that a 14-day treatment with a blood-brain barrier permeable histone deacetylase 6 (HDAC6) inhibitor successfully reverses long-term CICD following a therapeutic doxorubicin dosing schedule in female mice, as assessed by the puzzle box test …

“Translation Of Hdac6 Pet Imaging Using [18f]Ekz-001 – Cgmp Production And Measurement Of Hdac6 Target Occupancy In Nhps” – A Review, Dania Rahal

Chemistry & Biochemistry Undergraduate Honors Theses

The inhibition of histone deacetylase 6 (HDAC6) has been reported to alleviate the effects of neurodegenerative diseases such as Alzheimer’s disease. The brain-penetrant PET radioligand [¹⁸F]EKZ-001 has high affinity and selectivity towards HDAC6 and therefore suggests great promise in therapeutic treatment studies and development for neurodegenerative diseases. “Translation of HDAC6 PET imaging using [¹⁸F]EKZ-001 – cGMP production and measurement of HDAC6 target occupancy in NHPs” has achieved an effective, fully automated method of producing [¹⁸F]EKZ-001 in compliance with current good manufacturing practices (cGMP) to support the translation of [¹⁸F]EKZ-001 PET for …

Synthesis, Structural Characterization, And In Vitro Biological Assessment Of Trans- Platinum (Ii) Thionate Complexes As Potent Anticancer Agents, Mia Alshami

Chemistry & Biochemistry Undergraduate Honors Theses

The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as a strategy to potentially overcome the …

Author Correction: Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Correction to: Scientific Reports https://doi.org/10.1038/s41598-019-47255-9, published online 29 July 2019

The original Article contained an error in Figure 1A where the control trace for both the HEK-AMY3 and HEKWT cells was duplicated...

The original Article has been corrected.

Oleyl Conjugated Histidine-Arginine Cell-Penetrating Peptides As Promising Agents For Sirna Delivery, Muhammad Imran Sajid, Dindyal Mandal, Naglaa Salem El-Sayed, Sandeep Lohan, Jonathan Moreno, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Recent approvals of siRNA-based products motivated the scientific community to explore siRNA as a treatment option for several intractable ailments, especially cancer. The success of approved siRNA therapy requires a suitable and safer drug delivery agent. Herein, we report a series of oleyl conjugated histidine–arginine peptides as a promising nonviral siRNA delivery tool. The conjugated peptides were found to bind with the siRNA at N/P ratio ≥ 2 and demonstrated complete protection for the siRNA from early enzymatic degradation at N/P ratio ≥ 20. Oleyl-conjugated peptide -siRNA complexes were found to be noncytotoxic in breast cancer cells (MCF-7 and MDA-MB-231) …

Characterisation Of Drug-Resistant Mycobacterium Tuberculosis Mutations And Transmission In Pakistan, Gary Napier, Anwar Sheed Khan, Abdul Jabbar, Muhammad Tahir Khan, Sajid Ali, Muhammad Qasim, Noor Mohammad, Rumina Hasan, Zahra Hasan, Susana Campino

Department of Pathology and Laboratory Medicine

Tuberculosis, caused by Mycobacterium tuberculosis, is a high-burden disease in Pakistan, with multi-drug (MDR) and extensive-drug (XDR) resistance, complicating infection control. Whole genome sequencing (WGS) of M. tuberculosis is being used to infer lineages (strain-types), drug resistance mutations, and transmission patterns-all informing infection control and clinical decision making. Here we analyse WGS data on 535 M. tuberculosis isolates sourced across Pakistan between years 2003 and 2020, to understand the circulating strain-types and mutations related to 12 anti-TB drugs, as well as identify transmission clusters. Most isolates belonged to lineage 3 (n = 397; 74.2%) strain-types, and were MDR (n = …

Geotemporospatial And Causal Inferential Epidemiological Overview And Survey Of Usa Cannabis, Cannabidiol And Cannabinoid Genotoxicity Expressed In Cancer Incidence 2003–2017: Part 1 - Continuous Bivariate Analysis, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Background

The genotoxic and cancerogenic impacts of population-wide cannabinoid exposure remains an open but highly salient question. The present report examines these issues from a continuous bivariate perspective with subsequent reports continuing categorical and detailed analyses.

Methods

Age-standardized state census incidence of 28 cancer types (including “All (non-skin) Cancer”) was sourced using SEER*Stat software from Centres for Disease Control and National Cancer Institute across US states 2001–2017. It was joined with drug exposure data from the nationally representative National Survey of Drug Use and Health conducted annually by the Substance Abuse and Mental Health Services Administration 2003–2017, response rate 74.1%. …

Geotemporospatial And Causal Inferential Epidemiological Overview And Survey Of Usa Cannabis, Cannabidiol And Cannabinoid Genotoxicity Expressed In Cancer Incidence 2003–2017: Part 2 – Categorical Bivariate Analysis And Attributable Fractions, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Background: As the cannabis-cancer relationship remains an important open question epidemiological investigation is warranted to calculate key metrics including Rate Ratios (RR), Attributable Fractions in the Exposed (AFE) and Population Attributable Risks (PAR) to directly compare the implicated case burden between emerging cannabinoids and the established carcinogen tobacco. Methods: SEER*Stat software from Centres for Disease Control was used to access age-standardized state census incidence of 28 cancer types (including “All (non-skin) Cancer”) from National Cancer Institute in US states 2001–2017. Drug exposures taken from the National Survey of Drug Use and Health 2003–2017, response rate 74.1%. Federal seizure data provided …

Geotemporospatial And Causal Inferential Epidemiological Overview And Survey Of Usa Cannabis, Cannabidiol And Cannabinoid Genotoxicity Expressed In Cancer Incidence 2003–2017: Part 3 – Spatiotemporal, Multivariable And Causal Inferential Pathfinding And Exploratory Analyses Of Prostate And Ovarian Cancers, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Background: The epidemiology of cannabinoid-related cancerogenesis has not been studied with cutting edge epidemiological techniques. Building on earlier bivariate papers in this series we aimed to conduct pathfinding studies to address this gap in two tumours of the reproductive tract, prostate and ovarian cancer. Methods: Age-standardized cancer incidence data for 28 tumour types (including “All (non-skin) Cancer”) was sourced from Centres for Disease Control and National Cancer Institute using SEER*Stat software across US states 2001–2017. Drug exposure was sourced from the nationally representative household survey National Survey of Drug Use and Health conducted annually by the Substance Abuse and Mental …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Agents, David Salehi, Saghar Mozaffari, Khalid Zoghebi, Sandeep Lohan, Dindyal Mandal, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of cyclic peptides, [(DipR)(WR)₄], [(DipR)₂(WR)₃], [(DipR)₃(WR)₂], [(DipR)₄(WR)], and [DipR]₅, and their linear counterparts containing arginine (R) as positively charged residues and tryptophan (W) or diphenylalanine (Dip) as hydrophobic residues, were synthesized and evaluated for their molecular transporter efficiency. The in vitro cytotoxicity of the synthesized peptides was determined in human epithelial ovary adenocarcinoma cells (SK-OV-3), human lymphoblast peripheral blood cells (CCRF-CEM), human embryonic epithelial kidney healthy cells (HEK-293), human epithelial mammary gland adenocarcinoma cells (MDA-MB-468), pig epithelial kidney normal cells (LLC-PK1), and human epithelial …