Pharmacology, Toxicology and Environmental Health Commons^™

Lenvatinib, Inderbir S. Padda, Mayur S. Parmar

HPD Articles

No abstract provided.

Covid (Sars-Cov-2) Vaccine, Inderbir S. Padda, Mayur S. Parmar

HPD Articles

No abstract provided.

Aducanumab, Inderbir S. Padda, Mayur S. Parmar

HPD Articles

No abstract provided.

Obeticholic Acid, Kristina Krupa, Vera Hapshy, Hiep Nguyen, Mayur S. Parmar

HPD Articles

No abstract provided.

Analysis Of Hba1c, Medication Compliance, Income Subsidies, And Comorbidity In Medicare Type 2 Diabetics, Robert E. Lazarchik

Walden Dissertations and Doctoral Studies

Diabetes is one of America’s leading chronic diseases with comorbidities contributing to lower health statuses and increased health care costs. While it is known that lowering HbA1c reduces the deleterious effects of diabetes, the capability to identify people with diabetes at risk for uncontrolled HbA1c levels or developing comorbidities based on the compliance rates for different oral antihyperglycemic medication classes (OAMCs) and financial assistance programs does not yet exist. These quantitative longitudinal retrospective studies examined the association between medication compliance, using Proportion of Days Covered (PDC), by OAMC and Medicare financial aid programs, on predicting HbA1c levels and comorbidities in …

Neuroprotective Effects Of Farnesol On Motor And Cognitive Impairment Against 3- Nitropropionic Acid-Induced Huntington’S Disease, S. Deepa, Emdormi Rymbai, T. K. Praveen, J. Saravanan

The Thai Journal of Pharmaceutical Sciences

Objective: The purpose of this study is to evaluate the role of farnesol as a potential neuroprotective agent against 3-nitropropionic acid (3-NP) acid-induced Huntington’s disease (HD) by in vitro, in vivo, and in silico models. 3-NP acid-induced Huntington’s disease in male Wistar rats was used to evaluate the neuroprotective potential of farnesol. Materials and Methods: 3-NP (10 mg/kg/day) was used for the induction of disease, followed by treatment with 50 mg/kg and 100 mg/kg of farnesol for 7 days. The effect of farnesol on motor symptoms was evaluated using actophotometer and rotarod apparatus and effect of farnesol on learning and …

Morphological Changes In Dorsal Root Ganglia Macrophages Associated With Neuropathic Pain Mechanisms Suggest A Novel Target For Chronic Pain Therapy, Emily Kussick

CMC Senior Theses

The present study examined morphological changes in the dorsal root ganglia (DRG) following an innate immune stimulus. The importance of the DRG has increasingly become recognized in pain processing as more than just the home of primary afferent cell bodies. All sensory information passes through the DRG via the primary afferents, and on to the spinal cord. The primary afferents synapse with second-order neurons in the spinal cord that ascend towards the brain, where they transmit the pain signal to the limbic forebrain and/or the somatosensory cortex for processing. The DRG is an interesting niche to study at as it …

Human Regulatory T Cells Control Inflammation From Effector T Cells In Prediabetes, Rui Liu

Theses and Dissertations--Pharmacy

Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease. A T cell cytokine profile (Th17) from PBMCs can distinguish obese T2D from obese non-diabetes subjects. Individual T cell subsets interact with each other and the diverse subsets jointly determine overall inflammation. Cellular metabolism drives cytokine production of CD4⁺ T cells, and therefore contributes to inflammation in T2D. However, specific changes in metabolism and function of CD4⁺ T cells during the progression from lean healthy to obese and diabetic stages in people have not been clarified.

We hypothesize that human regulatory T cells (Treg) impact metabolism of effector …

Abc Transporters In Glioblastoma: Anticancer Drug Transport And Transporter Regulation At The Blood-Brain Barrier, Julia A. Schulz

Theses and Dissertations--Pharmacy

Glioblastoma is one of the deadliest cancers, with a median survival of only one year. Even after aggressive treatment consisting of surgical resection, radiation, and chemotherapy, most glioblastoma patients suffer from tumor recurrence within 6-9 months. One reason for treatment failure of anticancer drugs is the blood-brain barrier that protects the brain by impeding xenobiotic uptake from the blood. To this end, efflux transporters at the human blood-brain barrier, such as P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2), prevent many compounds, including anticancer drugs, from entering the brain. Thus far, approaches to deliver anticancer drugs across the blood-brain barrier …

Elucidating The Role Of The Tyrosine Phosphatase, Shp-2, In Regulation Of Pd-L1 Expression In Non-Small Lung Cancer Using Both Biochemical Analyses And Real-World Genomic Information, Keller Toral

Theses and Dissertations--Pharmacy

Immune checkpoint inhibitors (ICIs), especially those that target programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), have been shown to provide substantial clinical benefit in many patients with non-small cell lung cancer (NSCLC). While these therapeutic agents can be highly effective in the correct context, the biological systems that malignant cells draft from normal activities of the cell are poorly characterized. Tumor cell-specific expression of PD-L1 is likely important for clinical benefit from PD-1 and PD-L1 inhibitors. It is known that PD-L1 is inappropriately expressed in many cancers harboring mutations in the RAS family of genes. …

Achieving Better Care In Pennsylvania By Allowing Pharmacists To Practice Pharmacy, Travis Murray

Dickinson Law Review (2017-Present)

Traditionally, state legislatures implemented Prescription Drug Monitoring Programs (“PDMPs”) to assist prescribers, pharmacists, and law enforcement in identifying patients likely to misuse, abuse, or divert controlled substances. PDMP databases contain a catalog of a patient’s recent controlled substances that pharmacies have filled, including the date, location, the quantity of medication filled, and the prescribing health care provider. Prescribers in Pennsylvania have a duty to query the PDMP before prescribing controlled substances in most clinical settings. Pharmacists have a similar duty in Pennsylvania to dispense safe and effective medication therapy to patients and to screen patients for potential signs of misuse, …

Opioid Use Disorder: The Timeline For Medication Assisted Therapy, Alexander Cristofori

Capstone Showcase

Opioid Use Disorder is patterns of opioid use leading to withdrawal, giving up important life events in order to use opioids, and excessive time spent using opioids, to name a few diagnostic criteria. The clinical progression of the disorder involves periods of acute exacerbation and remission that are cyclic in nature. Treatment is most effective when it includes both pharmacological and psychosocial modalities, referred to as medication assisted therapy (MAT). Three drugs used commonly in MAT-based treatment for OUD from oldest to newest include Methadone, Buprenorphine-naloxone, and Naltrexone. Treatment program models that prioritize total abstinence from the addictive substance attached …

Formulation And Evaluation Of Fast Disintegrating Tablets Of Domperidone Using Chitosan-Glycine Conjugates As Superdisintegrant, Simran Kaur Zandu, Reena Kumari, Inderbir Singh

The Thai Journal of Pharmaceutical Sciences

Purpose: The present research was envisaged to employ chitosan-glycine conjugates as superdisintegrant for developing fast disintegrating tablets of domperidone. Materials and Methods: Chitosan-glycine conjugates were prepared by physical mixing and microwave-assisted technique. Micromeritic study, Fourier transform infrared, scanning electron microscopy, and X-ray diffraction methods were employed for characterizing the powdered conjugates. The formulated FDTs were evaluated for wetting time, water absorption ratio, disintegration time, in vitro drug release, and other tablet parametric tests. Results and Discussion: The effective pore radius of unadulterated chitosan was found to be 18.45±1.27 μm whereas the chitosan-glycine conjugates prepared by physical technique and microwave technique …

Development And Radiosynthesis Of A Novel Bifunctional Tri-Γ-Glutamic Acid Polypeptide For Gallium-68 Labeling, Wanchai Chongcharoen, Shuichi Shiratori

The Thai Journal of Pharmaceutical Sciences

Radiosynthesis of a novel bifunctional chelator for gallium-68 (Ga-68) chelation has been fabricated through peptide synthesis. Using of solid phase peptide synthesizer, linear structure of three repeating unit of glutamic acid was primarily generated. Protecting group of tert-butyl in intermediate was then cleaved and eventually yield as tri-γ-glutamic acid polypeptide (tri- γ-GAP). Mass spectrometry revealed m/z was 406.1378 that well corresponded with proposed structure of three repeating unit of glutamic acids. To label Ga-68 with synthesized tri-γ-GAP, the elution of 68GaCl3 was chelated to tri-γ-GAP with high temperature condition. It was subsequently purified through Sep-Pak C18 cartridge. Radio thin-layer chromatography …

Characterization Of Acyclovir-Isonicotinamide Cocrystal By Solvent Evaporation Method With Ethanol And Glacial Acetic Acid, Hansen Pradana Sutedjo, Agnes Nuniek Winantari, Roisah Nawatila

The Thai Journal of Pharmaceutical Sciences

Background: Acyclovir is used as the first-line therapy for genital herpes simplex virus, but acyclovir has low solubility and bioavailability. Acyclovir has a water solubility of 2.5 mg/ml at 37°C and belongs to Class IV according to the bioavailability classification system. Cocrystalization is a technology that can be used to improve the solubility of materials by modifying the physical properties of materials, such as melting points, stability, mechanical properties, and polymorphisms of materials. Materials and Method: This study aims to prepare cocrystal of acyclovir with isonicotinamide as coformer using different solvents, namely, ethanol and glacial acetic acid by solvent evaporation …

Doxepin Accelerates The Healing Process Of Burn Wounds In Mice, Elham Saberzadeh, Mohsen Zabihi, Ehsan Motaghi, Fatemeh Shishehbor

The Thai Journal of Pharmaceutical Sciences

Wound healing following a skin burn is still a concern due to poor effectiveness and the side effects of the available topical and systemic drugs. Doxepin hydrochloride is an approved antidepressant drug (Application No.: 022036) which is effective for the treatment of moderate pruritus in patients with eczema and atopic dermatitis. The current study has evaluated the effect of topical and systemic doxepin to improve the histopathologic process of second-degree burn wound in mice. The mice were divided into six groups (n = 6), including topical normal saline group, topical glycerin group, positive control group (topical phenytoin), topical doxepin 5% …

In Silico Approach For Hepatoprotective Activity Of Piper Crocatum Leaf Toward Cytochrome P450 2e1 Protein, I. Nyoman Ehrich Lister, Chrismis Novalinda Ginting, Ermi Girsang, Wahyu Widowati, Ika Adhani Sholihah

The Thai Journal of Pharmaceutical Sciences

Liver plays important roles in metabolism of harmful xenobiotics. Prolonged exposure to chemicals, daily dietary supplements, or pharmaceutical drugs may cause liver damage or hepatotoxicity. Acetaminophen is a well-known pharmaceutical drug causing hepatotoxicity through generation of reactive metabolite called N-acetyl-p-benzoquinone imine through Cytochrome P450 2E1 (CYP2E1) metabolism. In the present study, we intended to predict the possible hepatoprotective properties of red betel (Piper crocatum) leaves. Quantitative structure activity relationship (QSAR) was used to predict the antioxidant and anti-inflammatory potential of major compounds of red betel, namely, eugenol, isoeugenol, chavibetol, hydroxychavicol, and allylpyrocatechol. Molecular docking was performed to analyze binding mode …

Comparative Evaluation Of The Hepatoprotective Activity Of Methanol Leaf Extracts Of Pterocarpus Santalinoides Dc Obtained By Cold Maceration And Soxhlet Extraction Techniques, Thelma Ebele Ihedioha, Isaac Uzoma Asuzu, Aruh Ottah Anaga, John Ikechukwu Ihedioha

The Thai Journal of Pharmaceutical Sciences

Objectives: This study compared the hepatoprotective activity of Pterocarpus santalinoides cold maceration extract (PSCME) with P. santalinoides Soxhlet extract (PSSE). Materials and Methods: Phytochemical constituents of both extracts were determined. 45 albino rats, randomly assigned into 9 groups (1–9) of 5 rats each, were used for the study. Liver damage was induced in groups 1–8 using carbon tetrachloride (CCl4). Group 1 served as untreated control, Groups 2–7 were treated with 50, 250 or 500 mg/kg PSCME or PSSE, Group 8 was treated with 100 mg/kg silymarin, while Group 9 served as normal control. Treatment was done orally for 15 days. …

Teaching And Learning Of Smoking Cessation And Tobacco Control In The Pharmacy Program: A Cross-Sectional Survey Study, Pantira Parinyarux, Adinat Umnuaypornlert, Kornkaew Chanthapasa

The Thai Journal of Pharmaceutical Sciences

Introduction: Pharmacists play an important role in smoking cessation programs. A lack of knowledge among pharmacy students can create a barrier to providing smoking cessation support. Pharmacy training programs should integrate smoking cessation techniques into the core curriculum. Objective: We aimed to explore the current teaching practices for smoking cessation and tobacco control in pharmacy curricula in Thailand. Methods: A questionnaire surveying tobacco control curricula and teaching techniques were distributed to faculty members in all 19 pharmacy departments in Thailand. Results: Twenty-nine faculty members participated in this study. Most pharmacy programs start teaching smoking cessation and tobacco control in the …

Effects Of Acute And Chronic Nicotine Administration On Choice Of Probabilistic Outcomes, Katya A. Nolder

Graduate Theses, Dissertations, and Problem Reports (ETD)

Risky choice can be operationally defined as the choice for a larger, uncertain reinforcer over a smaller, certain reinforcer. Research suggests smokers engage in more risky or maladaptive decisions when compared to nonsmokers. The relation between nicotine and risky choice could benefit from further investigation, since nicotine is the active substance of tobacco products that maintains tobacco addiction. Acute nicotine administration has shown to alter risky choice; however, since the everyday smoker uses nicotine repeatedly, more research on chronic administration is warranted and would allow for assessment of tolerance or sensitization of these effects. The present study investigated effects of …

Protein Phosphatase 2a In Metformin’S Action In Primary Human Skeletal Muscle Cells, Aktham H. Mestareehi

Wayne State University Dissertations

Diabetes is a group of metabolic diseases characterized by hyperglycemia caused by defects in insulin secretion, insulin action, or both. Diabetes is associated with damage, dysfunction, and failure of various organs, such as the eyes, heart, kid-neys, and brain. Diabetes is mainly classified into type 1 (T1DM) and type 2 diabetes (T2D). Diabetes affects more than 34 million people in the USA (about 1 in 10) and more than 90% of diabetic patients have type 2 diabetes (T2D). Insulin resistance is a main characteristic feature of type 2 diabetes. Skeletal muscle insulin resistance is con-sidered to be the primary defect …

Targeted Combination Therapy Of Triple-Negative Breast Cancer, Ketki Bhise

Wayne State University Dissertations

TARGETED COMBINATION THERAPY OF TRIPLE-NEGATIVE BREAST CANCERby KETKI BHISE May 2021 Advisor: Dr. Arun Iyer Major: Pharmaceutical Sciences Degree: Doctor of Philosophy Triple Negative Breast Cancer (TNBC) accounts for 10-20% of the total breast carcinoma cases. There is no FDA-approved targeted therapy for TNBC due to lack estrogen, progesterone and HER-2. We have identified the role of a hypoxia biomarker, carbonic anhydrase IX (CAIX) in proliferation and metastasis of TNBC. Based on this observation, we have developed CAIX-targeted Doxorubicin (Dox) prodrug, abbreviated as DoxAtz. To improve the delivery of DoxAtz to the tumor, we developed long circulating liposomes (LipoDoxAtz) and …

Therapeutic Dual-Targeting Of Cytosolic And Mitochondrial One-Carbon Metabolism, Aamod Sanjeev Dekhne

Wayne State University Dissertations

One-carbon metabolism (1CM) is compartmentalized in the mitochondria and cytosol and generates a host of metabolites critical to tumor propagation. Although drug-targeting of cytosolic 1CM remains a clinically-relevant mainstay, development of clinically-useful agents targeting mitochondrial 1CM remains elusive. Of particular pharmacological interest is the mitochondrial 1CM enzyme, serine hydroxymethyltransferase2 (SHMT2). SHMT2 expression correlates with the oncogenic phenotype in lung, colon, breast, glioma, and liver cancer and, overall, is the fifth-most differentially expressed metabolic enzyme in cancer cell versus normal tissue. Despite the unequivocal oncogenic importance and therapeutic potential of SHMT2, there are no clinically relevant (i.e. active in vivo) inhibitors …

Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer

Theses and Dissertations

Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …

Pharmacophoric Evaluation Of 5-Ht2a And 5-Ht2b Serotonin Recpeptors, Prithvi Hemanth

Theses and Dissertations

Serotonin (5-HT) receptors represent a class of receptors involved in a variety of physiological processes including regulation of mood, perception, cognition, appetite, and heart function, and thus serve as drug targets of several drugs such as antipsychotic agents, hallucinogenic drugs, and appetite suppressant drugs. Due to the structural similarity of certain 5-HT receptor subtypes, particularly 5-HT₂ receptors (5-HT_2A, 5-HT_2B receptors) determination and refinement of pharmacophore models of these receptor subtypes can greatly improve the therapeutic efficacy of drugs that target them.

The goals of this study were to define and/or refine existing pharmacophore models for 5-HT …

Interclass Gpcr Heteromerization Affects Localization And Trafficking, Rudy Toneatti

Theses and Dissertations

Class A serotonin (5-hydroxytryptamine) 2A (5-HT_2AR) and class C metabotropic glutamate 2 receptors (mGluR2) are seven transmembrane receptors (7TMRs or G protein-coupled receptors – GPCRs) involved in multiple neuropsychiatric disorders including schizophrenia. Previous findings from our laboratory reported that 5-HT_2AR and mGluR2 are dysregulated in the prefrontal cortex of patients suffering from this psychiatric condition, although 5-HT_2AR’s expression was recovered in antipsychotic-medicated patients. Genome-wide association studies on schizophrenia reported that endosomal trafficking that regulates cell surface abundance of another 7TMR implicated in this disease (dopamine D2 receptor) can be altered. Ligand-activated receptors, including the …

The Cb1 Receptor Positive Allosteric Modulator, Zcz011, Attenuates Naloxone-Precipitated Withdrawal Signs In Oxycodone-Dependent Mice And Inhibits Small Intestinal Transit In Mice, Julien Dodu

Theses and Dissertations

The endogenous cannabinoid system tightly regulates a myriad of physiological and pathophysiological functions. Effects of cannabinoids in ameliorating opioid withdrawal signs has been known for decades. Naloxone precipitates several withdrawal signs (e.g., diarrhea, weight loss, jumps, paw flutters, and head shakes) in opioid dependent rodents. ∆⁹-tetrahydrocannabinol (THC) has been shown to ameliorate opioid withdrawal in mice through the activation of cannabinoid type-1 (CB₁) receptors. Inhibition of the endocannabinoid degradative enzymes also attenuates these withdrawal signs (i.e., diarrhea, weight loss, jumps, paw flutters, and head shakes) in opioid-dependent mice. Specifically, inhibition of fatty acid amide hydrolase (FAAH), …

Synthesis, Molecular Docking, And Biological Evaluation Of Novel 2-(3-Chlorophenyl) Quinoline-4-Carboxamide Derivatives As Potent Anti-Breast Cancer And Antibacterial Agents, Kailas W. Shinde, Prashant S. Kharkar, Chetan P. Shah, Shrimant V. Rathod

The Thai Journal of Pharmaceutical Sciences

Objectives: The study aims to synthesize and to evaluate the anti-breast cancer and antibacterial activity of some novel quinoline-4-carboxamide derivatives. Materials and Methods: A series of novel quinoline analogs 6a-6j with varied substituent (X = H, F, OCH3, NO2) were synthesized from aniline through multi-step reactions in good yields. All analogues were confirmed by spectral characterization, namely, FT-IR, MS, 1H-NMR, and 13C-NMR. All the molecules were evaluated for their anticancer activity against a breast cancer cell line, MDA-MB-231 by MTT assay, and antibacterial activity against Gram-positive bacteria (Staphylococcus aureus 6538p and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas …

Doxorubicin Modulates P-Glycoprotein Transcription Differently During Caco-2 Differentiation, Udomsak Udomnilobol, Suree Jianmongko

The Thai Journal of Pharmaceutical Sciences

P-glycoprotein (P-gp) is an efflux transporter protecting cells from various chemical threats. Upregulation of P-gp expression, mediated by reactive oxygen species (ROS), has been reported in doxorubicin-treated cells. However, during cell differentiation cellular redox status may vary. This study investigated the influence of cell differentiation on doxorubicin-mediated P-gp expression in Caco-2 cells, and its relation to cellular redox status. During 21-day culture, Caco-2 cells were divided into pre-, during-, and post-differentiation, based on total cell numbers, percentage of G0/G1 cells, and alkaline phosphatase activity. Our study demonstrated that Caco-2 cells were in a more reduced state on differentiation. At low …

Evaluation Of Acute Oral Toxicity Of Methanolic Fractions Of Sesbania Grandiflora Linn. Roots In Albino Mice, N. S. Vinay, S. Babitha, R. Nandeesh, S. Paramesh, E. Manjunath, J. P. Geetha, V. P. Veerapur, B. Swetha, H. V. Keerthi Prasanth

The Thai Journal of Pharmaceutical Sciences

Introduction: Although Sesbania grandiflora Linn. roots have valuable pharmacological effects, the comprehensive awareness about its toxicity potential has been lacking. Objectives: The objectives of the study were to assess the acute oral toxicity of methanolic fraction of S. grandiflora root (MFSGR). Materials and Methods: The female albino mice were divided into two groups (n = 5), one group served as normal control while the other treated with MFSGR (2000 mg/kg, p.o). Both the groups of mice were observed for 14 days for various parameters according to the Organization for Economic Cooperative and Development guidelines 425 TG. Results: Oral administration of …