Other Chemicals and Drugs Commons^™

Pharmacokinetics And Brain Uptake In The Rhesus Monkey Of A Fusion Protein Of Arylsulfatase A And A Monoclonal Antibody Against The Human Insulin Receptor, Ruben J. Boado, Jeff Zhiqiang Lu, Eric Ka-Wai Hui, Rachita K. Sumbria, William M. Pardridge

Pharmacy Faculty Articles and Research

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder of the brain caused by mutations in the gene encoding the lysosomal sulfatase, arylsulfatase A (ASA). It is not possible to treat the brain in MLD with recombinant ASA, because the enzyme does not cross the blood-brain barrier (BBB). In the present investigation, a BBB-penetrating IgG-ASA fusion protein is engineered and expressed, where the ASA monomer is fused to the carboxyl terminus of each heavy chain of an engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via receptor-mediated transport on the endogenous BBB insulin receptor, …

Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall

Dissertations & Theses (Open Access)

The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are …

Oxaliplatin And Oxaliplatin Derivatives: Synthesis, Characterization, And Reactivity With Biologically Relevant Ligands, Amy Poynter

Mahurin Honors College Capstone Experience/Thesis Projects

Oxaliplatin is a third generation anticancer drug that has proven to be successful in fighting ovarian and testicular cancer. We are interested in determining how oxaliplatin and oxaliplatin derivatives interact with proteins, as well as how that interaction is affected by the size and shape of these platinum compounds. We have synthesized oxaliplatin as it is used in cancer treatment, as well as similar platinum compounds with the same diaminocyclohexane ligand as oxaliplatin but with additional bulk added to the nitrogen atoms. We are reacting oxaliplatin with key amino acids, including methionine, and will be comparing the kinetics of this …

Pharmacokinetic/Pharmacodynamic (Pk/Pd) Modeling Of Anti-Neoplastic Agents, Daniel Lexcen, Ahmed H. Salem, Walid F. Elkhatib, Virginia Haynes, Ayman Noreddin

Pharmacy Faculty Books and Book Chapters

"Development of tumor resistance to chemotherapeutics is related to inherent tumor variations regarding sensitivity to chemotherapeutics and to sub-optimal dosing regimens, including variation in patient pharmacokinetics that result in suboptimal exposure of tumor cells to anti-neoplastic drugs [1, 2]. The rate and extent of drug efficacy depends on the extent of drug exposure at the tumor site and the time above the effective concentration [3]. In vitro models that incorporate these pharmacokinetic and pharmacodynamic (PK/PD) principles to optimize therapeutic response may be considered the method of choice for optimizing dosing schedules before translating data from static assays to animals and …

Application Of Pharmacokinetics/Pharmacodynamics (Pk/Pd) In Designing Effective Antibiotic Treatment Regimens, Ghada F. Ahmed, Ayman Noreddin

Pharmacy Faculty Books and Book Chapters

"Designing antibiotic dosing regimens is often not optimal and the dose-response relationship for most antibiotics is not well-known1. Both Pharmacokinetics (PK) and Pharmacodynamics (PD) are characteristics of antimicrobial agents that should be considered in the development of effective antibiotic therapy. By linking the concentration time profile at the site of action to the drug effect (PK/PD), the effect of varying dosage regimens against pathogens could be simulated enabling the identification of effective dosage strategies. It is known that inadequate antibiotic dosing could not only lead to a therapeutic failure, but also to the development of bacterial resistance. Importantly, the evolution …

Ginkgo Extract Egb761 Confers Neuroprotection By Reduction Of Glutamate Release In Ischemic Brain, Alexander Mdzinarishvili, Rachita K. Sumbria, Dorothee Lang, Jochen Klein

Pharmacy Faculty Articles and Research

Purpose - Ginkgo extract EGb761 has shown anti-edema and anti-ischemic effects in various experimental models. In the present study, we demonstrate neuroprotective effects of EGb761 in experimental stroke while monitoring brain metabolism by microdialysis. Methods - We have used oxygen-glucose deprivation in brain slices in vitro and middle cerebral artery occlusion (MCAO) in vivo to induce ischemia in mouse brain. We used microdialysis in mouse striatum to monitor extracellular concentrations of glucose and glutamate. Results - In vitro, EGb761 reduced ischemia-induced cell swelling in hippocampal slices by 60%. In vivo, administration of EGb761 (300 mg/kg) reduced cell degeneration and edema …

Bsa Nanoparticles For Sirna Delivery: Coating Effects On Nanoparticle Properties, Plasma Protein Adsorption, And In Vitro Sirna Delivery, Haran Yogasundaram, Markian Stephan Bahniuk, Harsh-Deep Singh, Hamidreza Montazeri Aliabadi, Hasan Uludag, Larry David Unsworth

Pharmacy Faculty Articles and Research

Developing vehicles for the delivery of therapeutic molecules, like siRNA, is an area of active research. Nanoparticles composed of bovine serum albumin, stabilized via the adsorption of poly-L-lysine (PLL), have been shown to be potentially inert drug-delivery vehicles. With the primary goal of reducing nonspecific protein adsorption, the effect of using comb-type structures of poly(ethylene glycol) (1 kDa, PEG) units conjugated to PLL (4.2 and 24 kDa) on BSA-NP properties, apparent siRNA release rate, cell viability, and cell uptake were evaluated. PEGylated PLL coatings resulted in NPs with ζ-potentials close to neutral. Incubation with platelet-poor plasma showed the composition of …

Quantitative Analysis Of Some Important Metals And Metalloids In Tobacco Products By Inductively Coupled Plasma-Mass Spectrometry (Icp-Ms), Syed Ghulam Musharraf, Muhammad Shoaib, Amna Jabbar Siddiqui, Muhammad Najam-Ul-Haq, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background: Large scale usage of tobacco causes a lot of health troubles in human. Various formulations of tobacco are extensively used by the people particularly in developing world. Besides several toxic tobacco constituents some metals and metalloids are also believed to pose health risks. This paper describes inductively coupled plasma-mass spectrometric (ICP-MS) quantification of some important metals and metalloids in various brands of smoked, sniffed, dipped and chewed tobacco products.

Results: A microwave-assisted digestion method was used for sample preparation. The method was validated by analyzing a certified reference material. Percentage relative standard deviation (% R.S.D.) between recovered …