Chemical and Pharmacologic Phenomena Commons^™

Modelling Β2ar Regulation, Sharat J. Vayttaden

Dissertations and Theses (Open Access)

The β2 adrenergic receptor (β2AR) regulates smooth muscle relaxation in the vasculature and airways. Long- and Short-acting β-agonists (LABAs/SABAs) are widely used in treatment of chronic obstructive pulmonary disorder (COPD) and asthma. Despite their widespread clinical use we do not understand well the dominant β2AR regulatory pathways that are stimulated during therapy and bring about tachyphylaxis, which is the loss of drug effects. Thus, an understanding of how the β2AR responds to various β-agonists is crucial to their rational use. Towards that end we have developed deterministic models that explore the mechanism of drug- induced β2AR regulation. These mathematical models …

Intratracheal Instillation Of Cerium Oxide Nanoparticles Induces Hepatic Toxicity In Male Sprague-Dawley Rats, Siva Krishna Nalabotu, Madhukar Babu Kolli, William E. Triest, Jane Y. Ma, Nandini Dpk Manne, Anjaiah Katta, Hari S. Addagarla, Kevin M. Rice, Eric R. Blough

MIIR Faculty Research

Background: Cerium oxide (CeO₂) nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO₂ nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats.

Methods and results: Compared with control animals, CeO₂ nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05). Consistent with these data, rats exposed to CeO₂nanoparticles also exhibited reductions in liver weight (P < 0.05) and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation, and accumulation of granular material. No histopathological alterations were observed in the kidney, spleen, and heart. Analysis of serum biomarkers suggested an elevation of acute phase reactants and markers of hepatocyte injury in the rats exposed to CeO₂ nanoparticles.

Conclusion: Taken together, these data suggest that intratracheal instillation …

Application Of Raman Spectroscopy To Lubricants, Lubricated Surfaces And Lubrication Phenomena, David W. Johnson

Chemistry Faculty Publications

Recent advances in lasers and detector technologies and the development of low-cost instruments and fiber-optic probes have brought about an explosion in the lubrication systems being studied by Raman spectroscopy. This article provides examples of the use of Raman spectroscopy in the study of lubrication phenomena, including the characterization of liquid lubricants, lubricant additives, and solid lubricants; the study of vapor-phase lubrication; and the use of coated nanoparticles as lubricants.

A Sodium Salt Of The Dimer Of Boronoterephthalic Acid Anhydride, Scott Simmons, Albert Fratini, Vladimir Benin

Chemistry Faculty Publications

The title compound, sodium bis­(6-carb­oxy-1-hy­droxy-3-oxo-1,3-dihydro-2,1-benzoxaborol-1-yl)oxidanium, Na+·C16H15B2O13-, was prepared in two steps from 2-bromo-p-xylene. Its crystal structure was determined at 140 K and has triclinic (P) symmetry. The compound presents a unique structural motif, including two units of the cyclic anhydride of boronoterephthalic acid, joined by a protonated, and thereby trivalent, oxonium center. Association in the crystal is realized by complementary hydrogen bonding of the carboxyl groups, as well as by coordination of the sodium cations to the oxygen centers on the five-membered rings.

Theoretical Investigation Of A Reported Antibiotic From The 'Miracle Tree' Moringa Oleifera, Michael Horwath, Vladimir Benin

Chemistry Faculty Publications

Moringa oleifera, sometimes called the “Miracle Tree,” has received international attention for its potential to improve health in impoverished tropical areas. In addition to high vitamin content in the leaves and pods, the tree contains compounds with antioxidant and antibacterial properties. This study focused on the theoretical investigation of the suggested structure of one antibacterial compound, “pterygospermin,” whose existence was proposed after some studies of the roots of M. oleifera. The structure of pterygospermin was first proposed by a research group working in the 1950s, but later studies have not found evidence of this compound and have instead …

Exhausted Or Unlicensed: Can Field-Of-Use Restrictions In Biotech License Agreements Still Prevent Off-Label Use Promotion After Quanta Computer?, Kristal M. Wicks

The University of New Hampshire Law Review

[Excerpt] “In the biotechnology (biotech) industry, companies must be increasingly aware of their intellectual property and how their licensing strategies can impact their rights. When licensing patented technology, it is common practice for biotech companies to include restricted field-of-use provisions in their license agreements. Such provisions permit a licensee to only use licensed technology in a defined field and restrict use or development in another field. This licensing strategy plays an important role within the biotech industry because it allows companies to more effectively control their intellectual property and to more efficiently research and develop pharmaceutical products.

A problem that …

Using Photoactive Vitamin Nanoparticles As Photodynamic Antimicrobial Chemotherapeutic (Pact) Agents To Treat Chronic Wounds, Rahul A. Khanke

All Capstone Projects

The objective of the proposed study is to develop new materials and methods to manage microbial growth in chronic wounds using phototherapy. Chronic wounds are considered as a worldwide health problem. The most common chronic wounds can be classified into three categories: venous ulcers, diabetic ulcers, and pressure ulcers. Venous ulcers, which usually occur in the legs, account for about 70% to 90% of chronic wounds and can become infected easily. Venous ulcers are sores that develop after veins in the legs have been damaged. These ulcers can penetrate deeply into the skin. Occasionally, if a venous ulcer persists for …

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 …

Regulation Of Alpha- And Beta-Actin Isoforms In The Contracting A7r5 Smooth Muscle Cell, Dawn Leah Brown-Turner

Theses, Dissertations and Capstones

Two isoforms of actin have been found to be present in A7r5 smooth muscle cells, α- and β-actin. This body of work sets out to examine the different regulatory factors of the two actin isoforms during smooth muscle contraction. The response of the actin isoforms to phorbol 12, 13-dibutyrate (PDBu) is markedly different. α-Actin remodels to podosomes around the periphery of the cell, while β-actin merely shortens. One protein involved in smooth muscle contraction induced by PDBu is protein kinase C (PKC). Two inhibitors of PKC, staurosporine and bisindolymaleimide, were used prior to PDBu stimulation and after PDBu stimulation to …

Preparation And Characterization Of Some Substituted Benzyl N-Nitrosocarbamates Containing An N-2-(Methylthio)Ethyl Or A Bis(2-Aminoethyl)Sulfide Functionality, Satya Venkata, Eric Shamo, Vladimir Benin

Chemistry Faculty Publications

The synthesis and characterization of some substituted benzyl N-nitrosocarbamates with an N-2-(methylthio)ethyl or a bis(2-aminoethyl)sulfide functionality is reported, as a part of a long-term goal to design and prepare novel photolabile structures that could be used as substances for controlled release of alkylating and/or crosslinking agents. The synthesis was accomplished by reaction of benzyl chloroformates with the corresponding amines, resulting in the preparation of carbamates. The latter were subsequently nitrosated, utilizing two different N-nitrosation methods, to yield the target structures.

Anti-Inflammatory Effects Of Ppar-Gamma In Surgical Brain Injury (Sbi), Amy Hyong

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Brain injury can be caused by neurosurgical procedures themselves, due to direct trauma, retractor stretch, intraoperative hemorrhage and electrocautery damage. As a result of this surgical brain injury (SBI) postoperative complications such as inflammation, brain edema, and cell death can occur in the susceptible brain areas. Cerebral inflammation is a known contributor to the pathophysiology of brain injury. Following brain injury, the release of inflammatory mediators facilitates the development of BBB breakdown, cerebral edema, oxidative stress and neuronal death, resulting in further tissue damage in the brain and poor neurological outcomes. This study evaluates whether the use of a …

Preparation Of Halogenated Derivatives Of Thiazolo[5,4-D]Thiazole Via Direct Electrophilic Aromatic Substitution, Vladimir Benin, Alan T. Yeates, Douglas Dudis

Chemistry Faculty Publications

Chlorination and bromination reactions of thiazolo[5,4-d]thiazole led to the generation of its mono- and dihalogenated derivatives. These are the first instances of successful direct electrophilic aromatic substitution in the thiazolo[5,4-d]thiazole ring system. X-ray analysis demonstrates that both 2-bromothiazolo[5,4-d]-thiazole and 2,5-dibromothiazolo[5,4-d]thiazole are planar structures, with strongly manifested π-stacking in the solid state. Theoretical analysis of the pyridine-catalyzed halogenation (MP2/6-31+G(d) and B3LYP/6-31+G(d)calculations) reveals that introduction of one halogen actually leads to a slightly enhanced reactivity towards further halogenation. Several halogenation mechanisms have been investigated: 1) The direct C-halogenation with N-halopyridine as electrophile; …

Targeted Drug Delivery Systems For Cancer Therapy, Antonio Clementi, Christine O'Connor, Mary Mcnamara, A. Mazzaglia, M. C. Aversa, A. Giuffrida

Conference Papers

The role of cyclodextrin’s (CD) in drug delivery has advanced in recent years and this may be attributed to its biocompatibility and well established synthesis. Chemical modification of CDs has shown to extend the physicochemical properties and the host capacity for a variety of drugs. β-CD has been widely used in the early stages of pharmaceutical applications because of its ready availability and its cavity size suitability for a wide range of drugs. Chemical modification of β-CD has proven to enhance aqueous solubilisation, microbiological stability and reduced toxicity in previous studies.1 Folate Receptors are over-expressed in several human cancers including …

C–N Bond Rotation And E–Z Isomerism In Some N-Benzyl-N-Methylcarbamoyl Chlorides: A Dft Study, Michael Horwath, Vladimir Benin

Chemistry Faculty Publications

The current report presents the first theoretical study of the restricted CN bond rotation in carbamoyl chlorides. Several N-benzyl-N-methylcarbamoyl chlorides were investigated, with varying pattern of substitution in the aromatic ring. Optimizations and frequency calculations were conducted employing DFT at the B3LYP/6-31+G(d) level of theory. Each of the studied structures exhibits a pair of rotamers (s-Z and s-E), generated upon rotation around the C(O)N bond. The s-E isomer is the global minimum in every case, but the preference for it is usually less than 1 kcal/mol. Two possible transition state structures were identified …

The Effect Of Caffeine And Ethanol On Flatworm Regeneration., Erica Leighanne Collins

Electronic Theses and Dissertations

Flatworms, or planarian, have a high potential for regeneration and have been used as a model to investigate regeneration and stem cell biology for over a century. Chemicals, temperature, and seasonal factors can influence planarian regeneration. Caffeine and ethanol are two widely used drugs and their effect on flatworm regeneration was evaluated in this experiment. Non-toxic levels of caffeine, a stimulant, and ethanol, a depressant, were determined. The tails of the flatworms were removed and the regeneration stage was analyzed every 3 days for 15 days to see the effect of these drugs alone and in combination on regeneration. For …

Studies On A 50s Ribosomal Precursor Particle As A Substrate For Erm E Methyltransferase Enzyme In Staphylococcus Aureus ., Indira Pokkunuri

Electronic Theses and Dissertations

Erythromycin is a macrolide antibiotic that inhibits not only mRNA translation but also 50S ribosomal subunit assembly in bacterial cells. An important mechanism of erythromycin resistance is the methylation of 23S rRNA by erm methyl transferase enzymes. We are interested in investigating the true substrate for methylation because it is known from our work and the work of others that fully assembled 50S subunits are not substrates for methylation. We have published a model for 50S ribosomal subunit formation where, the precursor particle that accumulates in erythromycin treated cells is a target for methyl transferase activity. Current studies are aimed …

Secondary N-Nitrosocarbamate Anions: Structure And Alkylation Reactions. A Dft Study, Vladimir Benin

Chemistry Faculty Publications

The current article reports theoretical studies (DFT: B3LYP/6-31+G(d)) on the structure and alkylation reactions of the anions of some secondary N-nitrosocarbamates, a class of ambident nucleophiles whose chemistry has been little explored. Several anions (1–4), with an increasing size of the carbamate alkyl (aryl) group were investigated, in an attempt to establish the influence of the size of that group on the thermal stability and regioselectivity of alkylation of the title anions. The conclusion is that thermal stability and the mode of reaction are affected significantly only in the presence of very large and branched carbamate groups. The thermal …

Preparation Of Some Substituted Terephthalic Acids, Susanna Branion, Vladimir Benin

Chemistry Faculty Publications

We report in detail the preparation of two substituted terephthalic acids: 2‐sulfomethylterephthalic acid (1) and 2‐phosphonoterephthalic acid (2). Efficient, short syntheses have been developed for both compounds. They are potentially useful monomers for construction of acid‐pendant polymer chains.

Preparation, Characterization And Dft Studies Of Some New N-Nitrosocarbamates And N-Nitrosoureas, Ragavan Narayanan, Helene Hedian, Eric Shamo, Vladimir Benin

Chemistry Faculty Publications

We are presenting the preparation, characterization and density functional theory (DFT) studies {B3LYP/6-31+G(d)) of several reiated classes of N-nitrosocarbamates and N-nitrosoureas. The iong-range goal is the design and preparation of compounds, which would undergo photochemical or hydrolytic decomposition, to yield stabilized cyclic cations that can serve as alkylating agents at various nucleophilic centers, including DNA bases.

Synthesis, Structural Studies And Desilylation Reactions Of Some N-2-(Trimethylsilyl)Ethyl-N-Nitrosocarbamates, Arpitha Thakkalapally, Vladimir Benin

Chemistry Faculty Publications

The present report describes the preparation and characterization of several N-2-(trimethylsilyl)ethyl-N-nitrosocarbamates, designed as precursors to thermally unstable secondary N-nitrosocarbamate anions via fluoride-assisted cleavage. X-ray structural studies demonstrate that the core N-nitrosocarbamate moiety has a nearly planar geometry, with an s-E orientation at the N–N bond. DFT calculations (B3LYP/6-31+G(d)) reproduce accurately the structural features of the title compounds and detailed conformational analysis at the same level of theory addresses the long-standing issue of preferred geometries for three classes of related structures: N-nitrosocarbamates, N-nitrosoureas and N-nitrosoamides. Desilylation studies demonstrate that both the …

Age Related Changes In Contractile Sensitivity To Cyclic Gmp And Intracellular Calcium Compartmentalization In Ovine Arteries, Surya Margono Nauli

Loma Linda University Electronic Theses, Dissertations & Projects

The study examines the hypothesis that maturation changes the ability of cGMP to produce cerebral vasodilatation and alters the relative intracellular calcium pool sizes in ovine arteries. In ovine basilars taken from near-term fetal and young adult sheep, 8- pCPT-cGMP relaxed potassium- and serotonin-induced tone with pD2 values of 4.4±0.1 and 4.9±0.1 (fetal basilar) and 4.0±0.1 and 4.7±0.1 (adult basilar), respectively. In fura-2 loaded arteries, 8-pCPT-cGMP significantly lowered increases in cytosolic calcium concentration induced by serotonin but not potassium regardless of age. When calcium sensitivity was calculated in the same arteries as the slope of the relation between calcium concentration …

Protein Adducts Of Iso[4]Levuglandin E2, A Product Of The Isoprostane Pathway, In Oxidized Low Density Lipoprotein, Robert G. Salomon, Wei Sha, Cynthia Brame, Kamaljit Kaur, Ganesamoorthy Subbanagounder, June O'Neil, Henry F. Hoff, L. Jackson Roberts Ii

Pharmacy Faculty Articles and Research

Levuglandin (LG) E₂, a cytotoxic seco prostanoic acid co-generated with prostaglandins by nonenzymatic rearrangements of the cyclooxygenase-derived endoperoxide, prostaglandin H₂, avidly binds to proteins. That LGE₂-protein adducts can also be generated nonenzymatically is demonstrated by their production during free radical-induced oxidation of low density lipoprotein (LDL). Like oxidized LDL, LGE₂-LDL, but not native LDL, undergoes receptor-mediated uptake and impaired processing by macrophage cells. Since radical-induced lipid oxidation produces isomers of prostaglandins, isoprostanes (isoPs), via endoperoxide intermediates, we postulated previously that a similar family of LG isomers, isoLGs, is cogenerated with isoPs. Now …

Increased Focal Adhesion Kinase- And Urokinase-Type Plasminogen Activator Receptor-Associated Cell Signaling In Endothelial Cells Exposed To Asbestos, A Barchowsky, B M. Lannon, L C. Elmore, M D. Treadwell

Dartmouth Scholarship

Exposure of low-passage endothelial cells in culture to nonlethal amounts of asbestos, but not refractory ceramic fiber-1, increases cell motility and gene expression. These changes may be initiated by the fibers mimicking matrix proteins as ligands for receptors on the cell surface. In the present study, 1- to 3-hr exposures of endothelial cells to 5 mg/cm2 of chrysotile asbestos caused marked cell elongation and motility. However, little morphological change was seen when chrysotile was added to cells pretreated with either mannosamine to prevent assembly of glycophosphatidylinositol (GPI)-anchored receptors or with herbimycin A to inhibit tyrosine kinase activity. Affinity purification of …

The Effects Of Xanthine Analogs On Neonatal Rat And Adult Mouse Respiration, Susan M. Reynolds

Masters Theses

Apnea, a prolonged cessation of breathing, is commonly seen in premature infants. This condition, in its severest form, can be lethal and is a suspected cause of sudden infant death syndrome (SIDS). Sometimes referred to as apnea of prematurity, recurrent apnea is presently being treated with respiratory stimulants known as methylxanthines (MX) such as theophylline and caffeine. The benefits of MXs are accompanied by central nervous system stimulation and cardiostimulation which may be detrimental to a premature infant. Theophylline (1,3-diMX) has been shown to produce some of its effects by antagonizing endogenous adenosine. Another xanthine, enprofylline (3-propylxanthine), is presently being …

Diazepam, Pentobarbital, And Methaqualone Effects On Several Behaviors In The Rat And Antagonism By Ro 15-1788, David J. Mokler, Richard H. Rech

Biomedical Sciences Faculty Publications

The sedative hypnotics may exert their effects through a number of different mechanisms. Diazepam interacts with a specific receptor linked to a GABA receptor and a CL ionophore (Skolnick and Paul, 1981) and enhances the binding affinity of the GABA receptor for its ligand. Barbiturates may act at an additional receptor linked to this complex (Olsen, 1981). The sites of action of methaqualone have yet to be defined. Recently Hunkeler et al. (1981) synthesized a new class of compounds, the imidazodiazepines, the prototype being Ro 15-1788. They showed that Ro 15-1788 inhibits 3H-Diazepam binding to brain synaptosomes, reverses diazepam-induced protection …

Characteristics Of The Recovery Of The Coenzyme A-Synthesizing Protein Complex From Saccharomyces Cerevisiae, Stanley Joseph Tarnowski Jr.

Theses and Dissertations (ETD)

A multienzyme complex contained in Bakers' yeast (Saccharomyces cerevisiae) which synthesizes CoA has been named the coenzyme A-synthesizing protein complex (CoA-SPC). The CoA-SPC has been shown to be insoluble in the crude Bakers' yeast cell lysate formed by exposing the yeast cell to ether and dry ice. Only after solubilization has this multienzyme complex been shown to catalyze the formation of bound dephospho-CoA utilizing the substrates adenosine triphosphate, D-pantothenic acid and L-cysteine. A low molecular weight component or components of the soluble fraction of the yeast cell and chloride ion appears to be responsible for the solubilization of CoA-SPC. This …

An Analysis Of Blood Cortisol Levels In Oral Surgery Patients Under Various Levels Of Intravenous Medication, Fred L. Bunch

Loma Linda University Electronic Theses, Dissertations & Projects

This study was designed to objectively evaluate each pharmacological component of the Loma Linda intravenous sedation technique. The results were evaluated as a function of stress as measured by plasma cortisol levels.

The study was conducted on fifty patients in groups of ten. Blood samples were taken at set procedure intervals during dental extraction of third molar teeth. A component of the Loma Linda technique was deleted from each of the groups to ascertain its role in sedation and relief of stress.

Results show a trend toward reduction of plasma cortisol levels as the procedure progresses, indicating a measure of …

The Improvement Of Peripheral Blood Flow During Hemorrhagic Hypotension Following Phenoxybenzamine Treatment Expressed In Terms Of Extracellular Potassium Shifts, Thomas J. Wera

Master's Essays (1922 - )

The study of plasma electrolytes notably, the potassium and sodium ions during hemorrhagic stress and other forms of shock, were once the subject of intense investigation (42). However, the advent of new investigative techniques enabled more complex, experimental designs and methods to be used in which it was possible to study the many other variables which exist as a result of shock regardless of cause. The proponents of the probable electrolyte mechanism in shock subsequently diminished in numbers until recent times.

It is felt by this author that recent renewal regarding the various ions, especially the cations, sodium and potassium …

The Conversion Of Cytidylic Acid To Deoxycytidylic Acid In Rat Kidney, Judith Marie Werderitsch

Master's Essays (1922 - )

Evidence was presented in 1949 by Bendich, Getler, and Brown (2), that the free pyrimidine base, cytosine, was not incorporated into the nucleotides of deoxyribonucleic acid (DNA). Further studies by Hammarsten, Reichard, and Saluste (9) with cytidine and those by Roll, Weinfeld, and Carroll (26) with cytidylic acid, showed that the nucleoside and nucleotide derivatives were well incorporated into DNA. These experiments indicated that the conversion of the riboside (or ribotide) to the deoxyribose form had occurred with the nucleosidic linkage intact. This theory was further substantiated by Rose and Schweigert (29) using cytidylic acid incorporation into the total viscera …

A Study Of The Diffusibility And Non-Diffusibility Of Magnesium And Calcium In Normal Blood Sera., Louis J. Halle

Electronic Theses and Dissertations

No abstract provided.