Pharmacy and Pharmaceutical Sciences Commons^™

Aluminum Bioavailability From The Approved Food Additive Leavening Agent Acidic Sodium Aluminum Phosphate, Incorporated Into A Baked Good, Is Lower Than From Water, Robert A. Yokel, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

There are estimates of oral aluminum (Al) bioavailability from drinking water, but little information on Al bioavailability from foods. Foods contribute ∼95% and drinking water 1–2% of the typical human's daily Al intake. The objectives were to estimate oral Al bioavailability from a representative food containing the food additive acidic sodium aluminum phosphate (acidic SALP), a leavening agent in baked goods. Rats were acclimated to a special diet that resulted in no stomach contents 14 h after its withdrawal. They were trained to rapidly consume a biscuit containing 1.5% acidic SALP. Oral Al bioavailability was then determined from a biscuit …

Chain-Modified Pyridino-N Substituted Nicotine Compounds For Use In The Treatment Of Cns Pathologies, Peter A. Crooks, Linda Dwoshin, Rui Xu, Joshua T. Ayers

Pharmaceutical Sciences Faculty Patents

Compounds for treating abuse of nicotinic receptor agonists, addiction to psychostimulant drugs, addiction to opiates, addiction to alcohol, addiction to tobacco products, addiction to nicotine, schizophrenia and related diseases, depression and related conditions, Alzheimer's disease, Parkinson's disease, irritable bowel syndrome, and colitis. The compounds competitively inhibit central nervous system acting nicotinic receptor agonists and act at the putative α3β2* and α4β2 neuronal nicotinic receptors in the central nervous system.

Camptothecin Intermediates And Prodrugs And Methods Of Preparation Thereof, Thomas G. Burke, Dennis P. Curran, Wu Du

Pharmaceutical Sciences Faculty Patents

The present invention relates to novel intermediates and prodrugs of camptothecin and related analogs.

Selective Parp-1 Targeting For Designing Chemo/Radio Sensitizing Agents, Marcos Oliveira

Pharmaceutical Sciences Faculty Patents

Poly(ADP-ribose) polymerase-1 (PARP-1) is a central signaling enzyme in a cell nucleus. PARP-1 is a target for the development of radio and chemo sensitizing agents in cancer treatment as well as providing protection from stroke. An SH3 domain and an SH3 ligand domain have now been discovered on the PARP-1 protein. These domains are involved in PARP-1 activation. This discovery makes possible the use of bioinformatics tools for the design of new drugs and strategies for drug target selection, specifically targeting the PARP-1 enzyme.

The Speciation Of Metals In Mammals Influences Their Toxicokinetics And Toxicodynamics And Therefore Human Health Risk Assessment, Robert A. Yokel, Stephen M. Lasley, David C. Dorman

Pharmaceutical Sciences Faculty Publications

Chemical form (i.e., species) can influence metal toxicokinetics and toxicodynamics and should be considered to improve human health risk assessment. Factors that influence metal speciation (and examples) include: (1) carrier-mediated processes for specific metal species (arsenic, chromium, lead and manganese), (2) valence state (arsenic, chromium, manganese and mercury), (3) particle size (lead and manganese), (4) the nature of metal binding ligands (aluminum, arsenic, chromium, lead, and manganese), (5) whether the metal is an organic versus inorganic species (arsenic, lead, and mercury), and (6) biotransformation of metal species (aluminum, arsenic, chromium, lead, manganese and mercury). The influence of speciation on metal …

Ky Pharmacists’ Perceptions On Medication Errors (Me): A Tool For Legitimate Discussions With The Kentucky Board Of Pharmacy?, J. D. Hammond

MPA/MPP/MPFM Capstone Projects

No executive summary.

Cis-2,6-Disubstituted Piperidines For The Treatment Of Psychostimulant Abuse And Withdrawal, Eating Disorders, And Central Nervous System Diseases And Pathologies, Linda P. Dwoskin, Peter A. Crooks, Marlon D. Jones

Pharmaceutical Sciences Faculty Patents

Cis-2,6-disubstituted piperdine analogs, or lobeline analogs, having the general formula...

To see the remainder of this abstract, please download this patent.

The Chemical Species Of Aluminum Influences Its Paracellular Flux Across And Uptake Into Caco-2 Cells, A Model Of Gastrointestinal Absorption, Yuzhao Zhou, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Aluminum (Al) can cause neurotoxicity, a low-turnover osteomalacia, and microcytic anemia. To test the null hypothesis that the chemical form (species) of Al does not influence its mechanism or rate of absorption from the gastrointestinal tract, Al flux across and uptake into Caco-2 cells was investigated. Caco-2 cells were grown on porous membranes mounted in vertical diffusion chambers or in 35-mm-diameter plastic cell culture dishes. When 8 mM ²⁷Al was introduced as the ion, citrate, maltolate, fluoride, or hydroxide, the apical to basolateral apparent permeability (P_app) of Al correlated highly with the P_app of lucifer yellow …

Manganese Distribution Across The Blood-Brain Barrier. Iv. Evidence For Brain Influx Through Store-Operated Calcium Channels, Janelle S. Crossgrove, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is a required co-factor for many ubiquitous enzymes; however, chronic Mn overexposure can cause manganism, a parkinsonian-like syndrome. Previous studies showed Mn influx into brain is carrier-mediated, though the putative carrier(s) were not established. Studies conducted with cultured bovine brain microvascular endothelial cells (bBMECs), which comprise the blood–brain barrier, revealed ⁵⁴Mn (II) uptake positively correlated with pH, was temperature-dependent, and was sodium- and energy-independent. Brain ⁵⁴Mn uptake correlated inversely with calcium (Ca) concentration, but ⁴⁵Ca uptake was unaltered by high Mn concentration. Lanthanum (La), a non-selective inhibitor of several Ca channel types, as well as …

Oligonucleotide Delivery Systems For Camptothecins, Thomas Burke, Ayhan S. Demir, Ashok J. Chavan, Danzhou Yang

Pharmaceutical Sciences Faculty Patents

Camptothecin drugs are stabilized in their antitumor active lactone form by complexation with an oligonucleotide including RNA or catalytic RNA. The oligonucleotide-camptothecin drug complex may be incorporated within a macromolecular assembly including both viral and non-viral oligonucleotide vectors. The invention allows combination gene and camptothecin drug therapy.

Synthases, Joseph Chappell, Kathleen R. Manna, Joseph P. Noel, Courtney M. Starks

Pharmaceutical Sciences Faculty Patents

Novel synthases and the corresponding nucleic acids encoding such synthases are disclosed herein. Such synthases possess an active site pocket that includes key amino acid residues that are modified to generate desired terpenoid reaction intermediates and products. Synthase modifications are designed based on, e.g., the three-dimensional coordinates of tobacco 5-epi-aristolochene synthase. with or without a substrate bound in the active site.

26Al-Containing Acidic And Basic Sodium Aluminum Phosphate Preparation And Use In Studies Of Oral Aluminum Bioavailability From Foods Utilizing 26Al As An Aluminum Tracer, Robert A. Yokel, Aaron A. Urbas, Robert A. Lodder, John P. Selegue, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

We synthesized ²⁶Al-containing acidic and basic (alkaline) sodium aluminum phosphates (SALPs) which are FDA-approved leavening and emulsifying agents, respectively, and used them to determine the oral bioavailability of aluminum incorporated in selected foods. We selected applicable methods from published syntheses (patents) and scaled them down (∼3000- and 850-fold) to prepare ∼300–400 mg of each SALP. The ²⁶Al was incorporated at the beginning of the syntheses to maximize ²⁶Al and ²⁷Al equilibration and incorporate the ²⁶Al in the naturally-occurring Al-containing chemical species of the products. Near infrared spectroscopy (NIR) and X-ray powder diffraction (XRD) were used …

Aluminium Content Of Some Foods And Food Products In The Usa, With Aluminium Food Additives, Salim M. Saiyed, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

The primary objective was to determine the aluminium (Al) content of selected foods and food products in the USA which contain Al as an approved food additive. Intake of Al from the labeled serving size of each food product was calculated. The samples were acid or base digested and analysed for Al using electrothermal atomic absorption spectrometry. Quality control (QC) samples, with matrices matching the samples, were generated and used to verify the Al determinations. Food product Al content ranged from < 1–27,000 mg kg⁻¹. Cheese in a serving of frozen pizzas had up to 14 mg of Al, from basic sodium …

Nanoscintillation Systems For Aqueous-Based Liquid Scintillation Counting, Russell J. Mumper, Michael Jay

Pharmaceutical Sciences Faculty Patents

The present invention relates to the use of nanoscintillation systems, or nanoparticles containing fluor molecules, that can be used to detect an electron-emitting or alpha-particle-emitting radioisotope in the absence of organic-solvents commonly used in organic-based liquid scintillation cocktails. The invention also relates to compositions and use of three oil-in-water microemulsion precursors that can be engineered rapidly, reproducibly, and cost-effectively to produce useful nanoparticles less than 100 nanometers.

Permeable, Water Soluble, Non-Irritating Prodrugs Of Chemotherapeutic Agents With Oxaalkanoic Acids, Peter A. Crooks, Tadeusz Cynkowski, Grazyna Cynkowska, Hong Guo, Paul Ashton

Pharmaceutical Sciences Faculty Patents

The present invention relates to the field of prodrugs of chemotherapeutic agents and method of use thereof.

2,6-Disubstituted Piperidines As Modulators Of Nicotinic Acetylcholine Receptor Mediated Neurotransmitter Release, Uptake And Storage, Peter A. Crooks, Linda P. Dwoskin, Dennis Keith Miller, Vladimir P. Grinevich, Seth Davin Norrholm, Guangrong Zheng

Pharmaceutical Sciences Faculty Patents

Compounds used for treating dependence on or withdrawal from a drug of abuse, for an eating disorder or for a CNS disease or pathology . . .

To see the remainder of this abstract, please download this patent.

Manganese Toxicokinetics At The Blood-Brain Barrier, Robert A. Yokel, Janelle S. Crossgrove

Pharmaceutical Sciences Reports

Increased manganese (Mn) use in manufacturing and in gasoline has raised concern about Mn-induced parkinsonism. Previous research indicated carrier-mediated brain entry but did not assess brain efflux.

Using in situ rat brain perfusion, we studied influx across the blood-brain barrier (BBB) of three predominant plasma Mn species available to enter the brain: Mn²⁺, Mn citrate, and Mn transferrin. Our results suggested transporter-mediated uptake of these species. The uptake rate was greatest for Mn citrate. Our results using the brain efflux index method suggested that diffusion mediates distribution from rat brain to blood.

To characterize the carriers mediating brain …

Pharmaceutical Formulation For Poorly Water Soluble Camptothecin Analogues, Tiang-Xiang Xiang, Bradley D. Anderson

Pharmaceutical Sciences Faculty Patents

The present invention provides a general method to retard the precipitation inception time for poorly water-soluble camptothecin analogues from a supersaturated solution by a chemical conversion approach via pH alteration. This method is successfully utilized to prepare stable parenteral formulations for silatecan 7-t-butyldimethylsilyl-10-hydroxycamptothecin (DB-67), a poorly water-soluble lipophilic camptothecin analogue, in aqueous solutions containing β-cyclodextrin sulfobutyl ether (SBE-CD) or other solubilizing agents. The formulations manufactured by this method are more simple and cost-effective, of higher doses and better quality in terms of manufacture loss and formulation stability, and can be free of organic solvents (e.g., DMSO or N-methyl-2-pyrrolidinone).

Synthases, Joseph Chappell, Kathleen R. Manna, Joseph P. Noel, Courtney M. Starks

Pharmaceutical Sciences Faculty Patents

Novel synthases and the corresponding nucleic acids encoding such synthases are disclosed herein. Such synthases possess an active site pocket that includes key amino acid residues that are modified to generate desired terpenoid reaction intermediates and products. Synthase modifications are designed based on, e.g., the three-dimensional coordinates of tobacco 5-epi-aristolochene synthase, with or without a substrate bound in the active site.

System And Method For Intranasal Administration Of Lorazepam, Daniel Wermeling

Pharmacy Practice and Science Faculty Patents

A therapeutic composition of lorazepam and its pharmaceutically acceptable derivatives are provided for intranasal administration of at least one predetermined volumetric unit dose in the form of a spray by means that delivers one or more therapeutically prescribed unit doses that are highly accurate as to the volume discharged and which leave no significant quantity of the composition in the delivery means.

Pathogen- Or Elicitor-Inducible Transcription Regulatory Element From The Tobacco 5-Epi-Aristolochene Synthase Gene And Plants Transformed Therewith, Joseph Chappell, Shaohui Yin, Catherine Cornett

Pharmaceutical Sciences Faculty Patents

A tobacco epi-5-aristolochene synthase transcriptional regulatory element functional in plants, plant tissue and in plant cells for pathogen inducible gene expression and a method for increasing the transcriptional expression of downstream genetic information in plants, plant tissue and plant cells are disclosed.

Synthases, Joe Chappell, Kathleen R. Manna, Joseph P. Noel, Courtney M. Starks

Pharmaceutical Sciences Faculty Patents

Novel synthases and the corresponding nucleic acids encoding such synthases are disclosed herein. Such synthases possess an active site pocket that includes key amino acid residues that are modified to generate desired terpenoid reaction intermediates and products. Synthase modifications are designed based on, e.g., the three-dimensional coordinates of tobacco 5-epi-aristolochene synthase, with or without a substrate bound in the active site.

Transdemal Delivery Of Opioid Antagonist Prodrugs, Audra L. Stinchcomb, Peter W. Swaan

Pharmaceutical Sciences Faculty Patents

A composition, a method and an apparatus for transdermally delivering an effective amount of opioid antagonists derived from prodrugs for treatment of eating disorders, narcotic dependence and alcoholism. In addition, the present invention relates to a composition, a method and an apparatus for transdermally delivering an effective amount of an opioid and opioid antagonist derived from an opioid agonist and one of an opioid antagonist and a prodrug for treatment of pain.

Synthases, Joe Chappell, Kathleen R. Manna, Joseph P. Noel, Courtney M. Starks

Pharmaceutical Sciences Faculty Patents

Novel synthases and the corresponding nucleic acids encoding such synthases are disclosed herein. Such synthases possess an active site pocket that includes key amino acid residues that are modified to generate desired terpenoid reaction intermediates and products. Synthase modifications are designed based on, e.g., the three-dimensional coordinates of tobacco 5-epi-aristolochene synthase, with or without a substrate bound in the active site.

Bridged Nicotine Compounds For Use In The Treatment Of Cns Pathologies, Peter A. Crooks, Linda P. Dwoskin, Rui Xu, Vladimir P. Grinevich

Pharmaceutical Sciences Faculty Patents

Pharmaceutical compounds comprising bridged nicotine analogs of N-octylnicotinium iodide (NONI) having selective antagonist properties at α3β2-containing nicotinic receptor subtypes, and compositions containing these compounds. The compounds and compositions are used to treat central nervous system pathologies.

Manganese Distribution Across The Blood-Brain Barrier. I. Evidence For Carrier-Mediated Influx Of Managanese Citrate As Well As Manganese And Manganese Transferrin, Janelle S. Crossgrove, David D. Allen, Bonny L. Bukaveckas, Susan S. Rhineheimer, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is an essential element and a neurotoxicant. Regulation of Mn movement across the blood–brain barrier (BBB) contributes to whether the brain Mn concentration is functional or toxic. In plasma, Mn associates with water, small molecular weight ligands and proteins. Mn speciation may influence the kinetics of its movement through the BBB. In the present work, the brain influx rates of ⁵⁴Mn²⁺, ⁵⁴Mn citrate and ⁵⁴Mn transferrin (⁵⁴Mn Tf) were determined using the in situ brain perfusion technique. The influx rates were compared to their predicted diffusion rates, which were determined from …

Synthases, Joseph Chappell, Kathleen R. Manna, Joseph P. Noel, Courtney M. Starks

Pharmaceutical Sciences Faculty Patents

Novel synthases and the corresponding nucleic acids encoding such synthases are disclosed herein. Such synthases possess an active site pocket that includes key amino acid residues that are modified to generate desired terpenoid reaction intermediates and products. Synthase modifications are designed based on, e.g., the three-dimensional coordinates of tobacco 5-epi-aristolochene synthase with or without a substrate bound in the active site.

Methods Of Making Modified Polypeptides, Joseph Chappell, Kathleen R. Manna, Joseph P. Noel, Courtney M. Starks

Pharmaceutical Sciences Faculty Patents

Novel polypeptides and the corresponding nucleic acids encoding such polypeptides are disclosed herein. The invention provides methods of making modified polypeptides by altering one or more amino acid residues involved in the active site of a preselected polypeptide.

Brain Uptake, Retention, And Efflux Of Aluminum And Manganese, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

My colleagues and I investigated the sites and mechanisms of aluminum (Al) and manganese (Mn) distribution through the blood-brain barrier (BBB). Microdialysis was used to sample non-protein-bound Al in the extracellular fluid (ECF) of blood (plasma) and brain. Brain ECF Al appearance after intravenous Al citrate injection was too rapid to attribute to diffusion or to transferrin-receptor-mediated endocytosis, suggesting another carrier-mediated process. The brain:blood ECF Al concentration ratio was 0.15 at constant blood and brain ECF Al concentrations, suggesting carrier-mediated brain Al efflux. Pharmacological manipulations suggested the efflux carrier might be a monocarboxylate transporter (MCT). However, the lack of Al …

Cis-2,6-Disubstituted Piperidines For The Treatment Of Psychostimulant Abuse And Withdrawal, Eating Disorders, And Central Nervous System Diseases And Pathologies, Linda P. Dwoskin, Peter A. Crooks, Marlon D. Jones

Pharmaceutical Sciences Faculty Patents

Cis-2,6-disubstituted piperdine analogs, or lobeline analogs, having the general formula:

To see the remainder of this abstract, please download this patent.