Pharmacy and Pharmaceutical Sciences Commons^™

Bioactivity And Chemical Investigations Of Pereskia Bleo And Pereskia Grandifollia., Sim Kae Shin

Student Works (2010-2019)

Ethnopharmacological data has been one of the common useful criteria in drug discovery. Pereskia bleo and Pereskia grandifolia (Cactaceae), commonly known as ‘Jarum Tujuh Bilah’ in Malay and ‘Cak Sing Cam’ in Chinese have long been used as natural remedies in Malaysia. The experimental approach in the present study was based on bioassay-guided fractionation. The crude methanol and fractionated extracts of both Pereskia spp. were initially investigated for their biological activities such as antioxidant, antimicrobial and cytotoxic effect against five human cancer cell lines, namely nasopharyngeal epidermoid carcinoma cell line (KB), cervical carcinoma cell line (CasKi), colon carcinoma cell line …

Chemical Constituents Of Cryptocarya Densiflora., Nurul Nazneem Wan Othman

Student Works (2010-2019)

The extraction of alkaloids from the Malaysian Cryptocarya densiflora has been carried out in this study. The alkaloids were extracted from the bark and leaves of this species using acid base extraction and the crude alkaloids obtained were subjected to extensive chromatographic techniques such as thin layer and column chromatography. The structural elucidation of the purified alkaloids were performed with the aid of spectroscopic methods i.e. 1H NMR, 13C NMR, 2D NMR, IR, UV and LCMS. Investigation of the alkaloidal content from the bark of Cryptocarya densiflora afforded six alkaloids and their structures were elucidated as laurotetanine 63, isocaryachine 64, …

Cytoprotective And Genoprotective Effects Of Aqueous Extracts Of Processed Pleurotus Sajor-Caju Fruiting Bodies On Hydrogen Peroxide-Induced Damage Of Human Peripheral Blood Mononuclear Cells., Mohamad Fairus Abdul Kadir

Student Works (2010-2019)

Pleurotus sajor-caju authority is one of the mushroom species that is widely grown in Malaysia. The present study was undertaken to evaluate the antioxidant, cytotoxic, cytoprotective, genotoxic and genoprotective activities of crude water extracts of this mushroom. Crude aqueous extracts were prepared from the fruiting bodies that had been processed at different temperatures such as P1: blanching (95°C ± 2°C), P2: sun drying (30°C ± 2°C), P3: freeze drying (-46°C ± 3°C) and different temperatures of oven drying (P4: 45°C, P5: 50°C, P5: 55°C and P6: 60°C ± 2°C respectively). Antioxidant capacity of all the extracts was determined using ferric …

Molecular Staging Estimates Occult Tumor Burden In Colorectal Cancer, Alex Mejia, Stephanie Schulz, Terry Hyslop, David S. Weinberg, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumor cells in regional lymph nodes are a key prognostic marker of survival and predictive marker of response to adjuvant chemotherapy in colorectal cancer. However, clinicopathologic techniques to detect lymph node metastases remain imperfect, and ~30% of patients with lymph nodes negative by histology (pN0) develop recurrent disease, reflecting occult metastases that escape detection. These observations underscore an unmet clinical need for accurate approaches to identify occult nodal metastases in colorectal cancer patients. GUCY2C is a receptor whose expression normally is restricted to intestinal epithelial cells, but is universally over-expressed by colorectal cancer cells. A prospective, multicenter, blinded clinical trial …

Differences In Hospital Glycemic Control And Insulin Requirements In Patients Recovering From Critical Illness And Those Without Prior Critical Illness, April D. Miller, Leslie M. Phillips, Richard M. Schulz, P Brandon Bookstaver, Celeste N. Rudisill

Faculty Publications

INTRODUCTION: Hospital patients recovering from critical illness on general floors often receive insulin therapy based on protocols designed for patients admitted directly to general floors. The objective of this study is to compare glycemic control and insulin dosing in patients recovering from critical illness and those without prior critical illness. METHODS: Medical record review of blood glucose measurements and insulin dosing in 25 patients under general ward care while transitioning from the intensive care unit (transition group) and 25 patients admitted directly to the floor (direct floor group). RESULTS: Average blood glucose did not differ significantly between groups (transition group …

Enzymology And Medicinal Chemistry Of N5-Carboxyaminoimidazole Ribonucleotide Synthetase : A Novel Antibacterial Target, Hanumantharao Paritala

Wayne State University Dissertations

N5-Carboxyaminoimidazole ribonucleotide synthetase (N5-CAIR synthetase), a key enzyme in microbial de novo purine biosynthesis, catalyzes the conversion of aminoimidazole ribonucleotide (AIR) to N5-CAIR. To date, this enzyme has been observed only in microorganisms, and thus, it represents an ideal target for antimicrobial drug development. Here we report structural and functional studies on the Aspergillus clavatus N5-CAIR synthetase and identification of inhibitors for the enzyme. In collaboration with Dr. Hazel Holden of the University of Wisconsin, the three-dimensional structure of Aspergillus clavatus N5-CAIR synthetase was solved in the presence of either Mg2ATP or MgADP and AIR. These structures, determined to 2.1 …

Preparation And Characterization Of Lyophilized Cyclodextrin Complexes Of A Hemisuccinate Ester Of Delta-9-Tetrahydrocannabinol For Transmucosal Delivery, Sampada Bhaskar Upadhye

Electronic Theses and Dissertations

Delta-9- Tetrahydrocannabinol (THC) is the primary active ingredient of the plant Cannabis sativa (marijuana), responsible for the majority of the pharmacological effects. The most promising clinical applications of THC approved by the Food and Drug Administration (FDA) are for the control of nausea and vomiting associated with chemotherapy and for appetite stimulation of AIDS patients suffering from anorexia and wasting syndrome. The only dosage form currently approved by FDA is an oral, soft gelatin capsule (e.g. Marinol®). In addition, orally administered THC from Marinol® has shown slow and variable absorption due to low oral solubility and first pass metabolism. Our …

Synthesis, Characterization And Biological Activity Of Copper (Ii) And Zinc (Ii) Complexes Of Thiosemicarbazones And Their N(4)-Substituted Derivatives Derived From 2,4-Dihydroxybenzaldehyde., Tan Kong Wai

Student Works (2010-2019)

Four thiosemicarbazones ligands (1-4) have been prepared with good yield by refluxing 2,4-dihydroxybenzaldehyde with thiosemicarbazide or N(4)-substituted thiosemicarbazide in ethanol or methanol. From these four ligands, 16 new ternary metal complexes (5-20) with the general formulation of M(B)L have been prepared from the reactions of metal acetates with 2,4-dihydroxybenzaldehyde N(4)-substituted thiosemicarbazone in the presence of N,N-heterocyclic base (M2+ = Zn2+ or Cu2+; B = 2,2'-bipyridine, (bpy); 1,10-phenanthroline, (phen); L2- = doubly deprotonated thiosemicarbazones = 2,4-dihydroxybenzaldehyde thiosemicarbazonato, (HT); 2,4-dihydroxybenzaldehyde 4-methylthiosemicarbazonato, (HM); 2,4-dihydroxybenzaldehyde 4-ethylthiosemicarbazonato, (HE) and 2,4-dihydroxybenzaldehyde 4-phenylthiosemicarbazonato, (HP)) These compounds have been characterized by elemental analyses, IR, UV-Vis, NMR and magnetic …

Novel Cinnamic Acid-Based Dehydropolymers For Emphysema: In Vitro And In Vivo Assessment Of Their Activities, Bhawana Saluja

Theses and Dissertations

Pulmonary emphysema is a serious worldwide illness, causing progressive and irreversible alveolar wall loss and difficulty in breathing. It is caused mostly by cigarette smoking. However, its unresolved complex and multiple pathogenic mechanisms have left this disease without effective pharmacotherapy. This project hypothesized that cinnamic acid-based dehydropolymers (DHPs), originally discovered as novel anti-coagulants, protect against emphysema through their potent triple inhibitory actions against oxidative stress, inflammation and elastase, some of the pathogenic mechanisms associated with this disease. Three in vitro inhibitory activity assays for oxidative stress, lung inflammation and neutrophil elastase (NE) were developed and used to identify the most …

Modulation Of The Alpha-7 Nicotinic Acetylcholine Receptor Following Experimental Rat Brain Injury Improves Cellular And Behavioral Outcomes, Thomas Matt Woodcock

University of Kentucky Doctoral Dissertations

Traumatic brain injury (TBI) is a leading cause of death and long-term disability worldwide, and survivors are often left with cognitive deficits and significant problems with day to day tasks. To date, therapeutic pharmacological treatments of TBI remain elusive despite numerous clinical trials. An improved understanding of the molecular and cellular response to injury may help guide future treatment strategies. One promising marker for brain injury is the translocator protein (TSPO), which is normally expressed at a low level, but is highly expressed following brain damage and is associated with neuroinflammation. The isoquinoline carboxamide PK11195 binds selectively to the TSPO …

Pk/Pd Modelling Of Comb-Shaped Pegylated Salmon Calcitonin Conjugates Of Differing Molecular Weights, Sinead Ryan, Jesus Maria Frias, David H. Haddleton, David J. Brayden

Articles

Salmon calcitonin (sCT) was conjugated via cysteine-1 to novel combed-shaped end-functionalised poly(PEG) methyl ether methacrylate) (sCT-P) comb-shaped polymers, to yield conjugates of total molecular weights (MW) inclusive of sCT: 6.5, 9.5, 23 and 40 kDa. The conjugates were characterised by HPLC and their in vitro and in vivo bioactivity was measured by cAMP assay on human T47D cells and following intravenous (i.v.) injection to rats, respectively. Stability against endopeptidases, rat serum and liver homogenates was assessed. There were linear and exponential relationships between conjugate MW with potency and efficacy respectively, however the largest MW conjugate still retained 70% of E …

Resolution Of Clinical Signs In Trauma Intensive Care Unit Patients Following Diagnosis Of Ventilator-Associated Pneumonia, Kathryn A. Connor, Joseph M. Swanson, G. Christopher Wood, Bradley A. Boucher, Louis J. Magnotti

Pharmacy Faculty/Staff Publications

PURPOSE: The ATS/IDSA Ventilator-Associated Pneumonia (VAP) guidelines suggest that clinical improvement of VAP should be apparent within 3-6 days. Anecdotally, such improvement has not been noted in trauma patients at our institution. The current study was conducted to evaluate resolution of clinical signs of VAP following diagnosis.

METHODS: Critically injured adults admitted to the trauma intensive care unit (TICU) from 6/1/06-12/31/07 and subsequently diagnosed with VAP were retrospectively reviewed. Clinical signs, including derangements of maximum temperature (Tmax), white blood cell (WBC) count and Pa02/FiO2, were evaluated on days 1-16 following VAP diagnosis. Data are presented as mean ± SD unless …

Drug Release And Pharmacokinetic Properties Of Liposomal Db-67, Yali Liang

University of Kentucky Master's Theses

Sterically stabilized liposomes with saturated lipid as the major lipid component (DSPC:m-PEGDSPE were applied in DB-67 delivery. The drug retention in vitro and pharmacokinetic properties in vivo were investigated. Liposomal DB-67 was cleared faster from the circulation in the larger liposomes (~180 nm) than in the smaller ones (~120 nm), even though DB-67 was retained longer in smaller size liposomes in vitro. Liposomal DB-67 clearance was increased when cholesterol was present in the liposomal composition (40 mole %). It can be attributable to the faster drug release from cholesterol containing liposomes as compared to liposomes without cholesterol. Cholesterol free …

Role Of Oxidative Reactive Species And Antioxidants In Metabolism And Transport Of Therapeutic Drugs, Svetlana Verenich

Theses and Dissertations

Oxidative stress (OS) is a frequent complication of various disease conditions such as Alzheimer’s and Parkinson’s disease, atherosclerosis, preeclampsia, rheumatoid arthritis, diabetes including gestational diabetes, etc. OS is defined as an imbalance between the production of reactive species and the ability of an organism to detoxify the reactive intermediates and repair the damage. As a result of OS, the excess of reactive species such as oxygen superoxide (O2-), hydroxyl radical (OH), peroxynitrite (ONOO−), 4-hydroxynonenal (4HNE), etc., have a tendency to react with nearby proteins/nucleic acids/lipids changing their functionality or inactivating them completely. The organism has many ways to protect itself …

In-Vitro Metabolism And Protein Binding Of 5-Hmf, A Potential Antisickling Agent, Taghrid Obied

Theses and Dissertations

Purpose. 5-HMF is a potential antisickling agent forming a Schiff-adduct with hemoglobin (Hb). In-vitro studies were designed to identify the metabolic pathways of 5-HMF in human hepatic cytosol, to assess inter-species differences in its hepatic metabolism, and to predict in-vivo PK properties. Moreover, metabolism of 5-HMF in human RBCs was investigated. Finally, in-vitro studies were done to characterize 5-HMF binding kinetics with human Hb and albumin (HSA). Methods. NAD+ reduction was monitored at 340 nm in human hepatic cytosol for 5-HMF (26 mM) and prototypical ADH and ALDH substrates in the presence or absence of their inhibitors. Furthermore, concentration-dependency studies …

Prediction Of Human Systemic, Biologically Relevant Pharmacokinetic (Pk) Properties Based On Quantitative Structure Pharmacokinetic Relationships (Qspkr) And Interspecies Pharmacokinetic Allometric Scaling (Pk-As), Prajakta Badri

Theses and Dissertations

This research developed validated QSPKR and PK-AS models for predicting human systemic PK properties of three, preselected, pharmacological classes of drugs, namely opioids, β-adrenergic receptor ligands (β-ARL) and β-lactam antibiotics (β-LAs) using pertinent human and animal systemic PK properties (fu,, CLtot, Vdss, fe) and their biologically relevant unbound counterparts from the published literature, followed by an assessment of the effect of different molecular descriptors on these PK properties and on the PK-AS slopes for CLtot and Vdss from two species (rat and dog). Lipophilicity (log (D)7.4) and molecular weight (MW) were found to be the most statistically significant and biologically …

Development Of Cytarabine Prodrugs And Delivery Systems For Leukemia Treatment, Bhupender S. Chhikara, Keykavous Parang

Pharmacy Faculty Articles and Research

Importance of the field: Cytarabine is a polar nucleoside drug used for the treatment of myeloid leukemia and non-Hodgkin’s lymphoma. The drug has a short plasma half-life, low stability, and limited bioavailability. Overdosing of patients with continuous infusions may lead to side effects. Thus, various prodrug strategies and delivery systems have been extensively explored to enhance the half-life, stability, and delivery of cytarabine. Among the recent cytarabine prodrugs, amino acid conjugate ValCytarabine and fatty acid derivative CP-4055 (in phase 3 trials) have been investigated for the treatment of leukemia and solid tumors, respectively. Alternatively, delivery systems of cytarabine have …

Practice Patterns For Antibiotic De-Escalation In Culture-Negative Healthcare-Associated Pneumonia, M. Schlueter, C. James, A. Dominguez, Laura V. Tsu, G. Seymann

Pharmacy Faculty Articles and Research

Background Published guidelines for the treatment of healthcare-associated pneumonia (HCAP) recommend initial broad-spectrum antibiotics with appropriate de-escalation based on culture results. Guideline recommendations are based on data from intubated patients, in whom cultures are easily obtained. The approach to antibiotic de-escalation for culture-negative patients has not been addressed. Consequently, there are no published reports that describe the current standard of practice. Patients and methods All patients admitted to a university hospital with a diagnosis of HCAP, as defined by use of a pneumonia orderset, were identified retrospectively over a 2-year period. Antibiotics prescribed on admission, during hospital stay, and on …

Hcmv Pus28 Initiates Pro-Migratory Signaling Via Activation Of Pyk2 Kinase, Jennifer Totonchy, Susan Varnum, Ryan Melnychuk, Patricia Smith, Ljiliana Pasa-Tolic, Janani I. Shutthanadan, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Background: Human Cytomegalovirus (HCMV) has been implicated in the acceleration of vascular disease and chronic allograft rejection. Recently, the virus has been associated with glioblastoma and other tumors. We have previously shown that the HCMV-encoded chemokine receptor pUS28 mediates smooth muscle cell (SMC) and macrophage motility and this activity has been implicated in the acceleration of vascular disease. pUS28 induced SMC migration involves the activation of the protein tyrosine kinases (PTKs) Src and Focal adhesion kinase as well as the small GTPase RhoA. The PTK Pyk2 has been shown to play a role in cellular migration and formation of cancer, …

Gene Delivery In The Equine Cornea: A Novel Therapeutic Strategy, Dylan G. Buss, Ajay Sharma, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To determine if hybrid adeno-associated virus serotype 2/5 (AAV5) vector can effectively deliver foreign genes into the equine cornea without causing adverse side effects. The aims of this study were to: (i) evaluate efficacy of AAV5 to deliver therapeutic genes into equine corneal fibroblasts (ECFs) using enhanced green fluorescent protein (EGFP) marker gene and (ii) establish the safety of AAV5 vector for equine corneal gene therapy.

Animal Material—Primary ECF cultures were harvested from healthy donor equine corneas. Cultures were maintained at 370C in humidified atmosphere with 5% CO2.

Procedure—AAV5 vector expressing EGFP under control of hybrid cytomegalovirus (CMV) + chicken …