Pharmacology Commons^™

Improving Risk-Based Decision Making (Rbdm) Effectiveness Through A Framework Which Integrates Knowledge And Risk, Martin Lipa, Valerie Mulholland, Anne Greene (Editor)

Level 3

This paper explores the emergence of the importance of knowledge in Risk-Based Decision Making (RBDM) and Quality Risk Management (QRM) through a detailed review of ICH Q9(R1) (Step 2) and presents a framework(the RKI cycle) to integrate knowledge and risk and associated six principles to operationalise it.

Implementation Of A Drive-Through Covid-19 Mass Vaccination Site: Experiences From Louvax–Broadbent In Louisville, Kentucky, Ruth Carrico, Sarah Beth Hartlage, Valenchia Brown Msn, Aprn, Fnp-C, Sarah M. Bishop, Luanne Didelot, William Hayden, Beverly Williams Coleman, Sarah Tan, Delanor Manson, Kellie Kane, Dawn Balcom, Paul Kern

The University of Louisville Journal of Respiratory Infections

Background: Response to the COVID-19 pandemic has required innovative approaches to vaccination, including methods to rapidly and safely immunize communities. A major challenge to such a response involved access to untapped healthcare worker resources. The Louisville, Kentucky, response involved the use of a large volunteer workforce to supplement local public health employees in planning and implementing a large-scale drive-through vaccination event. The objective of this manuscript was to outline processes involved in training a mass immunization workforce and implementating a large-scale COVID-19 community vaccination.

Approach: Competency-based and standardized training was provided for every volunteer before working their shift. Volunteers worked …

Body Mass Index (Bmi): A Screening Tool Analysis, Deepesh Khanna, Cadynce Peltzer, Payal Kahar, Mayur S. Parmar

HPD Articles

Body mass index (BMI), a measurement based on a person's height and weight, allows the classification of individuals into categories such as obese or overweight. With these classifications, we can assess risk for hypertension, diabetes, cancer, hypercholesterolemia, and other chronic diseases. Furthermore, childhood BMI serves as a prediction method for health and disease later in life. Along with BMI, researchers also study waist circumference and waist-to-hip ratio in correlation with the above-mentioned chronic illnesses. This brief review explores the associations between body mass index, waist circumference, and the waist-hip ratio as measurements and their capability as predictors for persistent conditions …

Repurposing Metformin And Antifolates For The Treatment Of Hepatocellular Carcinoma, Sherouk Mohamed Tawfik

Theses and Dissertations

Hepatocellular carcinoma (HCC), one of the most prevalent types of cancers worldwide, continues to maintain high levels of resistance to standard therapy. As clinical data revealed poor response rates, the need for developing new methods has increased to improve the overall wellbeing of patients with HCC. Due to its safety, wide availability and previously reported anti-cancer effects, metformin (MET) serves to be a possible therapeutic agent when combined with other well-known anti-cancer agents. The aim of this study was to investigate the potential anti-cancer effects of MET, an anti-diabetic agent, when combined with two antifolate drugs: trimethoprim (TMP) or methotrexate …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Measurement Of Binding Affinity And Receptor Activation Of A Novel Curcumin Analog, Cis-Trans Curcumin, At Adenosine Receptors A1, A2a, A2b, And A3, Luke James Hamilton

Biology Theses, Dissertations, and Student Creative Activity

Vanilloid phytochemicals (VPs), which contain the 4-hydroxy-3-methoxybenzyl group, have consistently been shown to alleviate pain. All four of the adenosine receptor (AR) subtypes mediate pain and have been targeted by pharmacologists to generate new therapeutics for pain. However, despite the fact that both VPs and ARs are connected to pain relief, only a few studies have described the interaction between VPs and ARs. Furthermore, the few studies that have been done have all been performed in vivo, with no assessment of binding affinity and receptor activation in vitro. In this study, photochemical methods were used to generate a novel isomer …

Breadth Of Vaccinated Cancer Patient Humoral Response To Sars-Cov-2 Spike Protein And Rbd Variants, Julia Corman, Joey Breckenridge Jr., Adrienne M. Bushau-Sprinkle, Krystal T. Hamorsky, Joshua L. Fuqua

Posters-at-the-Capitol

SARS-CoV-2, the virus responsible for the COVID-19 of which several variants have emerged, such as the B.1.351 SARS-CoV-2 variant. The Receptor Binding Domain (RBD), located within the Spike protein is an immunogenic epitope for potent neutralizing antibodies. Current mRNA vaccines encode for the Spike protein, allowing the body to build antigen-specific antibodies. Assays measuring protective antibodies are essential to manage the COVID-19 pandemic and can be used as a platform for variant screening. RBD-foldon 2.2 is a novel antigen produced by fusing RBD with the trimerization domain Fibritin from Bacteriophage T4. Its amino acid sequence is based on the original …

Wastewater-Based Estimation Of Substances Discharged At The Rest Areas Along The State Highways In Kentucky, Katherine E. Gray, Eugene Shin, Tyler Whitt, Andrew Windhorst, Houston Hampton, Chris Delcher, Bikram Subedi

Posters-at-the-Capitol

The availability of licit and illicit stimulants and its adverse consequences on public health has emerged as a major drug threat to communities in the United States. Despite several drug-involved traffic incidents along the interstate highways, this report represents the first comprehensive and quantitative report of drugs discharged at the rest areas along the interstate highways. In this National Institute of Justice-funded study, the amount of several discharged drugs focusing on stimulants but also including opioids and prescription antipsychotics are being measured in raw wastewater collected from five rest areas and a truck servicing facility using a state-of-the-art mass …

N, N-Dimethylacetamide Targets Neuroinflammation In Alzheimer’S Disease In In Vitro And Ex Vivo Models, Zenghui Wei

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disorder with no cure, accounting for 60-80% of cases of dementia. While the two pathologic hallmarks of AD, senile plaques from extracellular deposition of amyloid β-protein (Aβ) and tau-based neurofibrillary tangles (NFT), have been known for decades, the pathogenesis of AD remains unclear. In recent years, anti-neuroinflammatory treatment has entered the spotlight in AD research. In previous studies, we have shown that N,N-dimethylacetamide (DMA), a common drug excipient, is a potent anti-inflammatory agent. In the current work, we investigate the effect of DMA on neuroinflammation and its mechanism of action in in-vitro and ex-vivo …

Golimumab, Inderbir S. Padda, Rajat Bhatt, Mayur S. Parmar

HPD Articles

No abstract provided.

Repurposing An Anti-Epileptic Drug For The Treatment Of Glioblastoma, Anjali Yadav

Theses and Dissertations

Glioblastoma multiforme (GBM) is a grade IV malignant glioma. It is a highly proliferative form of brain tumor with 5-year survival rate ~ 5% indicating a high mortality rate. Current treatment strategies for GBM include surgery, radiation, and chemotherapy. Surgical resection is challenging due to vital function of brain and as GBM often metastasizes in different brain regions. Additionally, development of resistance against the standard of care drug temozolomide (TMZ) is a major challenge in GBM management. GBM is also shielded with the blood brain barrier (BBB) which prevents the entry of several drugs. Therefore, a new drug must overcome …

Small Interfering Rna (Sirna)-Based Therapy, Inderbir S. Padda, Arun U. Mahtani, Mayur S. Parmar

HPD Articles

No abstract provided.

Sodium-Glucose Transport Protein 2 (Sglt2) Inhibitors, Inderbir S. Padda, Arun U. Mahtani, Mayur S. Parmar

HPD Articles

No abstract provided.

Poststroke Seizure And Epilepsy: A Review Of Incidence, Risk Factors, Diagnosis, Pathophysiology, And Pharmacological Therapies, Joseph Phan, Mario Ramos, Theodore Soares, Mayur S. Parmar

HPD Articles

Stroke is the most common cause of epilepsy and ultimately leads to a decrease in the quality of life of those affected. Ischemic and hemorrhagic strokes can both lead to poststroke epilepsy (PSE). Significant risk factors for PSE include age < 65age less than 65 years, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), cortical involvement, and genetic factors such as TRPM6 polymorphism. The diagnosis of PSE is made by using imaging modalities, blood biomarkers, and prognostic criteria. Electroencephalography (EEG) is currently the gold standard to diagnose PSE, while new combinations of modalities are being tested to increase diagnostic specificity. This literature review uncovers a newly found mechanism for the pathology of poststroke epilepsy. The pathogenesis of early-onset and late-onset is characterized by sequelae of neuronal cellular hypoxia and disruption of the blood-brain barrier, respectively. Interleukin-6 is responsible for increasing the activity of glial cells, causing gliosis and hyperexcitability of neurons. Epinephrine, high-mobility group protein B1, downregulation of CD32, and upregulation of HLA-DR impact the pathology of poststroke epilepsy by inhibiting the normal neuronal immune response. Decreased levels of neuropeptide Y, a neurotransmitter, act through multiple unique mechanisms, such as inhibiting intracellular Ca accumulation and acting as an anti-inflammatory, also implemented in the worsening progression of poststroke epilepsy. Additionally, CA1 hippocampal resonant neurons that increase theta oscillation are associated with poststroke epilepsy. Hypertensive small vessel disease may also have an implication in the temporal lobe epilepsy by causing occult microinfarctions. Furthermore, this review highlights the potential use of statins as primary prophylaxis against PSE, with multiple studies demonstrating a reduction in incidence using statins alone, statins in combination with antiepileptic drugs (AEDs), and statins with aspirin. The evidence strongly suggests that the second generation AEDs are a superior treatment method for PSE. Data from numerous studies demonstrate their relative lack of significant drug interactions, increased tolerability, and potential superiority in maintaining seizure-free status.

The Effects Of Gestational Exposure To Buprenorphine Or Morphine On Offspring Development, Abigail Myers

Wayne State University Theses

The opioid crisis in the United States has grown to epidemic proportions with opioid dependence among pregnant women quadrupling from 1999-2014. Opioid-dependent pregnant women are commonly given opioid maintenance therapies (e.g., buprenorphine), but the developmental and neurological effects of these drugs on offspring development are poorly understood. Our study uses a translational rodent model to characterize the developmental consequences of gestational morphine (“MS”; mimicking opioid use disorder) or buprenorphine (“BUP”; mimicking opioid maintenance therapy) exposure on exposed offspring. Female rats started BUP (1.0 mg/kg) or MS (3-6.0 mg/kg) exposure 7 days before pregnancy to represent an established user and either …

Building Tools For Improved Modulation Of The Human Gabaa Receptor, A Central Nervous System Target For The Treatment Of Anxiety, Garrett Edward Zinck

Theses and Dissertations--Pharmacy

In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market.

The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABA_A receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABA_A receptor interaction suggests that …

Response Of Dopaminergic System To Cocaine Exposure, Recovery After Cocaine Abstinence, And Impact Of A Long-Acting Cocaine Hydrolase, Jing Deng

Theses and Dissertations--Pharmacy

Cocaine produces its physiological effects by targeting multiple proteins in the central nervous system, particularly by binding with dopamine transporter (DAT) to block the normal dopamine (DA) recycling process. This process along with the pleasure feeling would wear off shortly after the abstinence from the drug. However, chronic cocaine use is associated with neuroadaptations in the dopaminergic system, including increases in the density of DAT on plasma membrane of dopaminergic neurons. Given the critical role of DAT in neurotransmission, various studies have been carried out on animal models to learn its structure, function, and distribution. Long-standing evidence supports that DAT …

Evaluating The Effects Of Mechlorethamine On The Dermal-Epidermal Junction, Trishaal Janardhanam Raghavendra Rao

Theses and Dissertations

Sulfur Mustard (SM) is a chemical warfare agent first utilized on the battlefield more than 100 years ago. To the present time, no antidote to combat the dermatotoxicity of SM exists. Mechlorethamine (HN2) is a derivative of SM which is used in anticancer therapy. Dermal exposure of HN2 is associated with dermal-epidermal junction (DEJ) disruption (vesication) which limits its clinical usefulness. The primary purpose of the present study was to investigate the mechanisms of vesication caused by HN2 using an in vivo mouse ear vesicant model (MEVM). The ears of male or female C57BL/ 6J mice were exposed to a …

Aging, A Pathological Factor In Neurological Injury, Aruvi Vijikumar

Graduate Theses, Dissertations, and Problem Reports (ETD)

One of the main reasons for CNS drugs to fail in clinical development is not considering age as a risk factor while studying chronic age-related neurological/neurodegenerative diseases in preclinical studies. We first set out to gain a comprehensive understanding of the impact of age on various aspects (anatomical, immunological, and biochemical) in rodents that play a key role in determining the onset, progression, and evolution of disease severity. With advancing age, the vascular structure and function are compromised which is hypothesized to accelerate cognitive decline. The initial step toward developing novel therapeutics is to characterize the age-related vascular modifications. Utilizing …

Hemogram Results And Renal Function Before And After Administration Of Black Cumin Seed Oil In Healthy Volunteers, Titiek Hidayati, Akrom Akrom, Sagiran Sagiran, Indrayanti Indrayanti

The Thai Journal of Pharmaceutical Sciences

Black cumin seed oil (BSCO) is widely used to maintain health and strengthen the people of Indonesia’s immune system and proved to be safe for kidneys. However, the effect of BSCO usage in a healthy kidney is remaining unknown. This study was aimed to determine the impact of the 20-day administration of BCSO on kidney function in healthy volunteers. We conducted a pre- and post-control design trial in 36 healthy volunteers. The volunteers had to hold a valid health certificate from the hospital, be willing to be involved in the research as evidenced by their willingness to complete and sign …

Improved Virus Inhibition By Microencapsulated Monoclonal Antibody Against Porcine Epidemic Diarrhea Virus, Rachatapan Junchay, Patcharapong Thangsunan, Kittipat Supchukun, Jakarwan Yostawonkul, Sasithon Temisak, Kaewta Rattnapisit, Teerapong Yata, Waranyoo Phoolcharoen

The Thai Journal of Pharmaceutical Sciences

Porcine epidemic diarrhea virus (PEDV) has been affecting the swine industry, especially in suckling pigs with a high mortality rate. Among all the strategies to overcome PEDV, boosting mucosal immunity in the pig intestines through oral administration appears to be more efficient than other routes. However, there are biological obstacles such as an acidic environment that could damage biologics, a product from organisms often used for PEDV treatment. The plant-derived 2C10 monoclonal antibody (mAb) from Nicotiana benthamiana produced by transient expression was revealed as one of the potential candidates against PEDV through oral delivery. Herein, we demonstrated the calcium-alginate microencapsulation …

The Successful Treatment Of Brevundimonas Diminuta Using Ceftriaxone, In A Patient On Continuous Ambulatory Peritoneal Dialysis: A Case Report And Literature Review, Sukrit Kanchanasurakit, Natnicha Woranithipokin, Piyakamol Teeranaew, Natthawee Kaewrattanapatthama, Chotirat Nakaranurack

The Thai Journal of Pharmaceutical Sciences

Brevundimonas diminuta (B. diminuta) is found in the healthcare environment and in the community. At present, there are few reports of infections caused by this microorganism, especially in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). A 44-year-old woman undergoing CAPD was diagnosed with a B. diminuta infection. Ceftriaxone was given both intravenously and intraperitoneally. After treatment with ceftriaxone, the peritoneal dialysis fluid white cell count, neutrophil count, and symptoms improved. To the best of our knowledge, this is the first case report of a B. diminuta infection in a patient had undergoing CAPD in Thailand.

The Effect Of Pioglitazone On Phosphoproteome And Interactome Of Protein Phosphatase 2a In Primary Human Skeletal Muscle Cells, Lana Alghanem

Wayne State University Dissertations

Skeletal muscle insulin resistance is one of the main contributors to Type 2 Diabetes (T2D), which is a chronic disease affecting 37.3 million people in United States (US), with an estimated annual cost exceeding $300 billion in the US. T2D is being treated with a variety of medications, including Pioglitazone (PIO), a potent insulin sensitizer for skeletal muscle. PIO is a synthetic ligand for the peroxisome proliferator-activated receptor (PPAR-γ), nuclear receptors regulating the expression of many genes involved in lipid and glucose metabolism. To date, the molecular action of PIO that sensitizes muscle to insulin is incompletely understood. Protein phosphorylation …

The Susceptibility Of Penicillin, Ceftriaxone, And Cefotaxime Against Streptococcus Pneumoniae Isolated From Patients With Invasive Pneumococcal Diseases At A Teaching Hospital In Thailand, Jantima Traipattanakul, Sudaluck Thunyaharn, Juthathip Suphanklang, Wichai Santimaleeworagun

The Thai Journal of Pharmaceutical Sciences

Objective: Pneumococcal disease is a severe invasive infection causing morbidity and death, so the appropriate antimicrobials are greatly important. We aimed to determine the minimum inhibitory concentration (MIC) of penicillin, cefotaxime and ceftriaxone against S. pneumoniae. Methods: The clinical isolates were obtained from patients with invasive pneumococcal disease admitted to Phramongkutklao Hospital, Thailand over a period of 10 years between 2006 and 2015. The in vitro antimicrobial susceptibility testing of antibiotics including penicillin, ceftriaxone and cefotaxime against S. pneumoniae isolates were determined by E-test. The MIC range, MIC50, and MIC90 (μg/ml) and percentage of susceptible isolates were recorded. Results: Forty …

Prevalence, Distribution, Treatment, And Modern Methods For In Vitro Diagnosis Of Alzheimer’S Disease In India: Challenges And Future Prospective, Sopan Nangare, Pravin Patil

The Thai Journal of Pharmaceutical Sciences

In India, the plethora of evidence indicates that neurodegenerative conditions are a significant public health issue wherein over 4 million Indian peoples have been affected. For the past two decades, the prevalence of Alzheimer’s disease (AD) is growing rapidly in India that may due to the significant lack of health-care services and poor knowledge of AD and another form of dementia. Therefore, this in turn to develop ultramodern techniques for the efficient detection of AD biomarkers that helps to the prognosis and diagnosis of AD. Recently, significant progress has been observed in the area of AD that includes prognosis, and …

Gc-Ms Fingerprints Combined With Chemometric Analysis For The Authentication Of Morus Alba Leaves From Thailand, Malai Satiraphan, Aye Thida, Lawan Sratthaphut, Patcharawan Tanamatayarat, Onoomar Toyama

The Thai Journal of Pharmaceutical Sciences

Introduction: Morus alba L. is one of the economic plants in Thailand. Several varieties are grown in various parts of the country. Different varieties from different regions may produce dissimilar chemical fingerprints. Objectives: The gas chromatography coupled to mass spectrometry (GC-MS) fingerprints of 2 varieties of M. alba leaves from three locations in Thailand, along with tea products will be established. Materials and Methods: The GC-MS chromatograms combined with chemometric analysis were used to analyze the extracts of M. alba leaves and their tea products. Results: A total of 83 compounds comprising terpenes, saturated fatty acids, unsaturated fatty acids and …

Determination Of Sugars And Amino Acids In Japanese Wine Using Core-Shell Liquid Chromatography Tandem Electrochemical Detection, Kana Yoshimura, Aiko Sano, Ryuichiro Suzuki, Shun-Ichi Mitomo, Yukiko Negishi, Toshiki Mutai, Florencio Arce Jr., Gerard Lee See, Takashi Tanikawa

The Thai Journal of Pharmaceutical Sciences

In this study, sugars (glucose, fructose, and sucrose) and amino acids in plum and yuzu wines were quantified with a new and simple method involving an electrochemical detector (ECD) and core-shell column [S-30/70=St (styrene)/DVB (divinylbenzene)-5TMDAH (tetramethyldiaminohexane)]. Analysis was conducted under the following conditions: A column temperature (40°C), flow rate (0.3 mL/min), injection volume (20 μL), and mobile phase (0.1 mol/L NaOH). Glucose, fructose, and sucrose had retention times of 14.68 min, 16.22 min, and 19.29 min, respectively, when measured using an ECD. When the sugar content was compared among the plum wines, plum wine A had the lowest sugar content. …

Effect Of Chronic Kidney Disease On Warfarin Responsiveness Among Thai Patients, Sasimaporn Yaengkratok, Manat Pongchaidecha, Wichai Santimaleeworagun, Pornwalai Boonmuang

The Thai Journal of Pharmaceutical Sciences

This study aims to determine the effect of chronic kidney disease on warfarin response, including initial doses, maintenance doses, time in therapeutic range (TTR), and international normalized ratio (INR) variability. This is a retrospective cohort study at Rajavithi Hospital from 2015 to 2018. A total of 189 patients were included and divided into five groups based on estimated glomerular filtration rate (eGFR) (G1, eGFR ≥ 60 mL/min/1.73 m2; G2, 30–59 mL/min/1.73 m2; G3, 15–29 mL/min/1.73 m2; G4, ≤ 15 mL/min/1.73 m2; and G5, ≤ 15 mL/min/1.73 m2 with dialysis). The median age was 65.00 years, and 60.9% of patients were …

Neuroprotective And Nootropic Evaluation Of Myristica Malabarica On Diabetes-Induced Cognitive Impairment In Experimental Animals: Promising For Controlling The Risk Of Alzheimer’S Disease, Kolguri Jagadeeshwar, Rajasekhar Reddy Alavala, Subhakar Raju Ravula, Umasankar Kulandaivelu, G.S.N. Koteswara Rao

The Thai Journal of Pharmaceutical Sciences

This study intends to explore the neuroprotective and memory-enhancing properties of Myristica malabarica (MM) leaf extracts on diabetic-induced cognitive decline rats. The models of Y maze and Morris water maze were selected for nootropic activity and neuroprotective properties were deliberate by assessing the levels of Ach, malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), catalase (CAT) and glutathione hormone (GSH) in diabetic rat brains. Significantly improved memory and learning with 100 mg/kg (P < 0.01) and 200 mg/kg (P < 0.001) of EAMM (L) and MAMM (L) in Y maze and Morris water maze models. Significant effect was observed in all the extracts with two doses when compared with diabetic control on day 75. The levels of AChE (P < 0.001), MDA (P < 0.01), and NO (P < 0.05) were decreased significantly and significantly raised (P < 0.01) levels of SOD, CAT, and GSH with MAMM (100 and 200 mg/kg) compared with disease control. Further studies on MM leaf are needed as evidence of cognitive impairment in defense against diabetes has been shown to expose its mode of action.

Fluid Properties Of Solvents And Oils Used In In Situ Forming Microparticles, Sai Myo Thu Rein, Torsak Intaraphairot

The Thai Journal of Pharmaceutical Sciences

In situ forming microparticle (ISM) has been recently used as the injectable drug delivery system prepared from polymeric non-aqueous phase in oil emulsion. Solvents and oils used in ISM including N-methyl pyrrolidone (NMP), 2-pyrrolidone (PYR), dimethyl sulfoxide (DMSO), glycofurol, triacetin, olive oil, camellia oil and isopropyl myristate (IPM) were evaluated for pH, density, viscosity, flow time, surface tension, contact angle, color distribution, injectability, antimicrobial activities and cytotoxicity. The most viscous camellia oil and olive oil showed the highest flow time with lowest color diffusion and lower injectability; thus, they were suitable for performing as external phase of ISM to prolong …