Medicine and Health Sciences Commons^™

The Translational Regulation Of Lipoprotein Lipase In Diabetic Rats Involves The 3′-Untranslated Region Of The Lipoprotein Lipase Mrna, Gouri Ranganathan, Chunling Li, Philip A. Kern

Clinical and Translational Science Faculty Publications

Adipose tissue lipoprotein lipase (LPL) activity is decreased in patients with poorly controlled diabetes, and this contributes to the dyslipidemia of diabetes. To study the mechanism of this decrease in LPL, we studied adipose tissue LPL expression in male rats with streptozotocin-induced diabetes. Heparin releasable and extractable LPL activity in the epididymal fat decreased by 75-80% in the diabetic group and treatment of the rats with insulin prior to sacrifice reversed this effect. Northern blot analysis indicated no corresponding change in LPL mRNA levels. However, LPL synthetic rate, measured using [³⁵S]methionine pulse labeling, was decreased by 75% in …

Phosphonated Agents And Their Antiangiogenic And Antitumorigenic Use, Delwood C. Collins, Antonio Gagliardi, Peter Nickel

Obstetrics and Genecology Faculty Patents

Phosphonic acid agents are synthesized and characterized which are potent inhibitors of angiogenesis, tumorigenesis and metalloproteinase activity. Their method of use for the inhibition of angiogenesis and metalloproteinase and the treatment of tumors is also shown.

Combined Antagonist Compositions, Scott R. Hamann

Anesthesiology Faculty Patents

Novel compositions of a combination of nicotinic, opioid, serotonergic and/or adrenergic antagonists in combination with nicotinic and opioid agonists, anti-depressants, stimulants, non-steroidal anti-inflammatory drugs, and local anesthetics, such combinations being useful in the treatment of excitable system disorders, pain and psychiatric disorders, and methods of use thereof.

Estrogen-Induced Relaxation In Bovine Coronary Arteries In Vitro: Evidence For A New Mechanism, Jelica D. J. Kalenic, Rolando J. Ramirez, Stanley Einzig, William A. Neal, Hatim A. Omar

Pediatrics Faculty Publications

Numerous studies have shown estrogen to be vasoactive in various circulations. Our objective was to determine the effect of estrogen on isolated bovine coronary arteries and the possible mechanism. Bovine coronary arteries, precontracted with thromboxane mimetic U₄₆₆₁₉ were given doses (0.01-30μM) of 17Β-estradiol in the presence and absence of endothelium and these inhibitors: 10μM indomethacin (cyclooxygenase inhibitor), 10μM methylene blue (inhibits soluble guanylate cyclase), 100μM nitro-L-arginine (inhibits nitric oxide synthesis), 100μM isobutylmethylxanthine (phosphodiesterase inhibitor) and 30μM mifepristone (Ru₃₈₄₈₆ steroid receptor antagonist). Our results indicated that, estrogen, in the highest concentration used (30μM), elicited an acute dose-dependent relaxation of …

The Toxicology Of Aluminum In The Brain: A Review, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Aluminum is environmentally ubiquitous, providing human exposure. Usual human exposure is primarily dietary. The potential for significant Al absorption from the nasal cavity and direct distribution into the brain should be further investigated. Decreased renal function increases human risk of Al-induced accumulation and toxicity. Brain Al entry from blood may involve transferrin-receptor mediated endocytosis and a more rapid process transporting small molecular weight Al species. There appears to be Al efflux from the brain, probably as Al citrate. There is prolonged retention of a fraction of Al that enters the brain, suggesting the potential for accumulation with repeated exposure. Al …

Combination Anti-Leukimic Therapy By Utilizing Suramin And Biologic Response Modifiers, Michael A. Doukas

Internal Medicine Faculty Patents

A method of treating leukemia which includes administering an effective amount of composition comprising suramin and a biological response modifier, wherein the suramin and the biological response modifier show synergistic or additive anti-leukemic activity. A pharmaceutical composition is also disclosed.

Sarcocystis Neurona Diagnostic Primer And Its Use In Methods Of Equine Protozoal Myeloencephalitis Diagnosis, Clara K. Fenger, David E. Granstrom, Alvin A. Gajadhar, Jitender P. Dubey

Veterinary Science Faculty Patents

An amplification primer and probe which can be used in an in vitro diagnostic test for the presence of S. neurona in equine blood or cerebrospinal fluid. Sarcocystis neurona is responsible for the equine condition of protozoal myelitis. The amplification primer is seventeen nucleotides in length and complementary to a unique section of the small ribosomal subunit of Sarcocystis neurona. The primer encompasses nucleotide positions 1470-1487 of the small ribosomal subunit of S. neurona. The primer has the sequence 5' CCATTCCGGACGCGGGT SEQ ID NO:1.

Method Of Treatment Of Conditions Associate With Oxidative Tissue Damage, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Compositions containing as the active ingredient a spin-trapping reagent, preferably α-phenyl butyl nitrone (PBN) or spin-trapping derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient are disclosed for treating or preventing symptoms associated with aging or other conditions associated with oxidative tissue damage. Other spin-trapping agents can also be used, such as 5,5-dimethyl pyrroline N-oxide (DMPO) or α-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), and other spin-trapping derivatives thereof. These compositions and methods are useful in the treatment of age-related disorders, pre-surgical and/or pre-anesthetic preparation or administration of chemotherapeutic agents, and in the treatment of disorders or trauma of the brain, …

Pathogen-Inducible Regulatory Element, Joseph Chappell, Catherine A. G. Cornett, Shauhui Yui

Pharmaceutical Sciences Faculty Patents

Qualitative transcriptional regulatory sequences functional in plants, plant tissue and in plant cells for inducible gene expression and quantitative transcriptional regulatory sequences for increasing the transcriptional expression of downstream genetic information in plants, plant tissue and plant cells are disclosed. Also disclosed are methods and recombinant DNA molecules for improving the disease resistance of transgenic plants, especially wherein an inducible promoter controls the expression of a protein capable of evoking the hypersensitive response in a plant.

Phosphonated Agents And Their Antiangiogenic And Antitumorigenic Use, Delwood C. Collins, Antonio Gagliardi, Peter Nickel

Obstetrics and Genecology Faculty Patents

Phosphonic acid agents are synthesized and characterized which are potent inhibitors of angiogenesis, tumorigenesis and metalloproteinase activity. Their method of use for the inhibition of angiogenesis and metalloproteinase and the treatment of tumors is also shown.

Use Of Lobeline Compounds In The Treatment Of Central Nervous System Diseases And Pathologies, Peter A. Crooks, Linda P. Dwoskin

Pharmaceutical Sciences Faculty Patents

Lobeline and nicotine evoke [³H]overflow from rat striatal slices preloaded with [³H]dopamine ([³H]DA). The lobeline-evoked overflow is calcium-independent and not antagonized by mecamylamine, suggesting a mechanism of action other than the stimulation of nicotinic receptors. Whereas nicotine stimulates nicotinic receptors, lobeline inhibits [³H]DA uptake into synaptic vesicles and striatal synaptosomes. The results suggest that different mechanisms are responsible for the increase in striatal DA release evoked by lobeline and nicotine. [³H]-Dihydrotetrabenazine [³H]DTBZ), used routinely to probe a high-affinity binding site-on the vesicular monoamine transporter (VMAT2) binds to vesicle …

Chronic Arsenic Exposure And Risk Of Infant Mortality In Two Areas Of Chile, Claudia Hopenhayn-Rich, Steven R. Browning, Irva Hertz-Picciotto, Catterina Ferreccio, Cecilia Peralta, Herman Gibb

Preventive Medicine and Environmental Health Faculty Publications

Chronic arsenic exposure has been associated with a range of neurologic, vascular, dermatologic, and carcinogenic effects. However, limited research has been directed at the association of arsenic exposure and human reproductive health outcomes. The principal aim of this study was to investigate the trends in infant mortality between two geographic locations in Chile: Antofagasta, which has a well-documented history of arsenic exposure from naturally contaminated water, and Valparaíso, a comparable low-exposure city. The arsenic concentration in Antofagasta's public drinking water supply rose substantially in 1958 with the introduction of a new water source, and remained elevated until 1970. We used …

Fatal Injuries Due To Logs Rolling Off Trucks At Sawmills, Kentucky Injury Prevention And Research Center

Kentucky Haz Alerts--Tractors/Logging

Logging is one of the most hazardous occupations in the nation as well as Kentucky. During 1994-1998, 45 fatalities in Kentucky were related to logging. Of those deaths, 7 were due to logs rolling off trucks at sawmills. The workers were all males and aged 31-64 years. Their experience varied from less than 1 year to more than 25 years. Below are brief case reports of three fatal events, followed by recommendations for prevention of similar events.

Formulations For Sustained-Release Of Topical Anesthetics And Methods Of Making And Using Same, Michael Joseph Jay, G. Thomas Kluemper, Sang Hun Kim

Pharmaceutical Sciences Faculty Patents

The present invention provides, inter alia, formulations useful to ameliorate symptoms associated with mucosal abrasions, specifically those due to dental orthodontic brackets; oral surgery; periodontal surgery or other procedures. For instance, there is a formulation comprising: 65 to 75% microcrystalline wax; 5 to 15% non-ionic polymer; 15 to 25% topical anesthetic; and 1 to 5% surfactant, wherein the ratio of non-ionic polymer to microcrystalline wax is no greater than 0.2. Preferably, for solid topical anesthetics, the particle size is less than the apertures of a 100-mesh screen. However, the topical anesthetic may also be a liquid. Formulations wherein the mixture …

Chemical Isoprenoid Synthases And Uses Thereof, Joseph Chappell, Kyoungwhan Back

Pharmaceutical Sciences Faculty Patents

Disclosed is a chimeric isoprenoid synthase polypeptide including a first domain from a first isoprenoid synthase joined to a second domain from a second, heterologous isoprenoid synthase, whereby the chimeric isoprenoid synthase is capable of catalyzing the production of isoprenoid reaction products that are not produced in the absence of the second domain of the second, heterologous isoprenoid synthase. Also disclosed is a chimeric isoprenoid synthase polypeptide including an asymmetrically positioned homologous domain, whereby the chimeric isoprenoid synthase is capable of catalyzing the production of isoprenoid reaction products that are not produced when the domain is positioned at its naturally-occurring …

Angiotensin Ii Promotes Atherosclerotic Lesions And Aneurysms In Apolipoprotein E-Deficient Mice, Alan Daugherty, Michael W. Manning, Lisa A. Cassis

Gill Heart & Vascular Institute Faculty Publications

Increased plasma concentrations of angiotension II (Ang II) have been implicated in atherogenesis. To examine this relationship directly, we infused Ang II or vehicle for 1 month via osmotic minipumps into mature apoE^–/– mice. These doses of Ang II did not alter arterial blood pressure, body weight, serum cholesterol concentrations, or distribution of lipoprotein cholesterol. However, Ang II infusions promoted an increased severity of aortic atherosclerotic lesions. These Ang II–induced lesions were predominantly lipid-laden macrophages and lymphocytes; moreover, Ang II promoted a marked increase in the number of macrophages present in the adventitial tissue underlying lesions. Unexpectedly, pronounced abdominal …

Host-Derived Signals For Inducing Isoprenoid Gene Expression And Uses Thereof, Joseph Chappell, Marcos Lusso

Pharmaceutical Sciences Faculty Patents

Disclosed is a method for preparing a composition that is capable of activating the expression of a gene involved in the synthesis of an isoprenoid, the method involving: (a) contacting a plant cell with an elicitor under conditions that allow an elicitor-induced release of a compound that activates the synthesis of an isoprenoid; and (b) recovering a composition including the compound, wherein the compound is diffusible and has a molecular weight less than or equal to 10,000 daltons. Also disclosed is a substantially pure elicitor-induced composition, the composition being capable of activating a gene involved in the synthesis of a …

Regulation Of Acetylated Low Density Lipoprotein Uptake In Macrophages By Pertussis Toxin-Sensitive G Proteins, Stewart C. Whitman, Alan Daugherty, Steven R. Post

Gill Heart & Vascular Institute Faculty Publications

Class A scavenger receptors (SR-A) mediate the uptake of modified low density lipoprotein (LDL) by macrophages. Although not typically associated with the activation of intracellular signaling cascades, results with peritoneal macrophages indicate that the SR-A ligand acetylated LDL (AcLDL) promotes activation of cytosolic kinases and phospholipases. These signaling responses were blocked by the treatment of cells with pertussis toxin (PTX) indicating that SR-A activates G_i/o-linked signaling pathways. The functional significance of SR-A-mediated G_i/o activation is not clear. In this study, we investigated the potential role of G_i/o activation in regulating SR-A-mediated lipoprotein uptake. Treatment of mouse …

Means To Achieve Sustained Release Of Synergistic Drugs By Conjugation, Paul Ashton, Peter A. Crooks, Tadeusz Cynkowski, Grazyna Cynkowska, Hone Guo

Ophthalmology and Visual Science Faculty Patents

A codrug composition of at least two drug compounds covalently linked to one another via a labile bond to form a single codrug composition, or ionically linked to one another to form a single workings composition, and methods of use of the codrug for the treatment of various medical conditions. The codrug may be administered by itself or in the form of a bioerodible or nonbioerodible substance.

How Much Asthma Is Occupationally Related?, David M. Mannino

David M. Mannino

Asthma is a chronic respiratory disease that is increasing in both prevalence and mortality in developed countries around the world. Occupational exposures to sensitizers and irritants are causes of both asthma cases and asthma exacerbations in adults. The determination of how many cases of asthma may be caused or worsened by occupational exposures is highly dependent on how asthma is defined, what constitutes work-relatedness, and what specific methodology is employed. Surveillance-based methods generally have found the lowest proportion of work-related asthma, ranging from 1-8% of cases. Other types of studies, using exposed-unexposed methodology or interviews of incident asthma cases, have …

Population-Based Survey Of Complementary And Alternative Medicine Usage, Patient Satisfaction, And Physician Involvement, Robert Oldendick, Ann L. Coker, Darryl Wieland, James I. Raymond, Janice C. Probst, Bruce J. Schell, Carleen H. Stopskopf

CRVAW Faculty Journal Articles

Background. With an increasing proportion of Americans using complementary or alternative medicine (CAM), physicians need to know which patients are using CAM to effectively manage care.

Methods. In this cross-sectional study, telephone interviews were conducted with 1,584 South Carolina adults (ages 18 and older); 66% responded to the survey of demographics, general health, frequency of CAM use, perceived CAM effectiveness, and physician knowledge of CAM use.

Results. A total of 44% had used a CAM during the past year. Increasing age and higher education were significantly associated with CAM use. More than 60% perceived CAM therapy as very effective, and …

Novel Function Of Phosphoinositide 3-Kinase In T Cell Ca2+ Signaling, Ao-Lin Hsu, Tsui-Ting Ching, Goutam Sen, Da-Sheng Wan, Subbarao Bondada, Kalwant S. Authi, Ching-Shih Chen

Pharmaceutical Sciences Faculty Publications

This study presents evidence that phosphoinositide (PI) 3-kinase is involved in T cell Ca²⁺ signaling via a phosphatidylinositol 3,4,5-trisphosphate PI(3,4,5)P₃-sensitive Ca²⁺entry pathway. First, exogenous PI(3,4,5)P₃ at concentrations close to its physiological levels induces Ca²⁺ influx in T cells, whereas PI(3,4)P₂, PI(4,5)P₂, and PI(3)P have no effect on [Ca²⁺]_i. This Ca²⁺ entry mechanism is cell type-specific as B cells and a number of cell lines examined do not respond to PI(3,4,5)P₃ stimulation. Second, inhibition of PI 3-kinase by wortmannin and by overexpression of the …

Cervical Pathology In West Virginia Adolescents, Hatim A. Omar, Patricia Callahan, Sanu Aggarwal, Kathaleen Perkins, Kathy Young

Pediatrics Faculty Publications

Cytologic screening is an important diagnostic tool used to detect precancerous and cancerous lesions of the cervix. We studied the prevalence of cervical abnormalities, based on Pap smear results, in patients at the Outpatient Adolescent Clinic at West Virginia University. We found a high incidence of overall intraepithelial cell pathology (24%) in this group with 2.4% high grade and 9.9% low-grade lesions. These findings show that major cervical pathology is present in this age group. Furthermore, repeat smears at intervals of < one year were performed on 317 patients. Of these repeat smears, 7% changed from normal to abnormal in this period. Sexually active adolescent females should have Pap smears at least annually to detect abnormalities that may otherwise not be detected until they are more advanced and difficult to manage. Higher risk adolescents may need semiannual screening.

Fungal Ipc Synthase Assay, Jeffery Radding, Robert C. Dickson, Robert L. Lester

Molecular and Cellular Biochemistry Faculty Patents

The presently-disclosed IPC synthase-inhibitor assays comprise the steps of: (1) expression of the IPC1 gene in a cell; (2) introducing labeled starting substrates for ceramide conversion as well as potential inhibitor(s) of such conversion to the expressed gene product in an environment which allows time and conditions for conversion, and (3) identifying those potential inhibitors which actually inhibit conversion. The present invention also provides methods to determine the ability of a test compound to inhibit fungal growth, comprising the steps of (1) presenting active inositolphosophotidylceramide synthase in a manner such that synthesis of inositolphosphotidylceramide can occur; (2) introducing ceramide and …

Effect Of Amitraz And Xylazine On Some Physiological Variables Of Horses, A. Queiroz-Neto, A. B. Carregaro, G. Zamur, J Daniel Harkins, Thomas Tobin, M. I. Mataqueiro, S. C. Gonçalves

Maxwell H. Gluck Equine Research Center Faculty Publications

The effect of the intravenous injection of amitraz (0.1 mg/kg) to horses on cardiac activity, respiratory rate, intestinal motor activity, rectal temperature, sweating and masticating was evaluated and compared to the effect of intravenous administration of xylazine (1mg/kg, iv) on heart rate, respiratory rate and intestinal activity. Amitraz caused a significant decrease in heart activity, respiratory rate and intestinal movements, but these effects were not as pronounced as those caused by xylazine. Amitraz also caused a significant relaxation of the rectal smooth muscle, and an apparent increase in sweating and in the frequency of horses found masticating hay. Rectal temperature …

Intimate Partner Violence Among Men And Women In South Carolina, 1998, Ann L. Coker, Christina Derrick, Julia L. Lumpkin, Robert Oldendick, R H. Potter

CRVAW Faculty Journal Articles

Few studies provide population-based estimates of intimate partner violence (IPV) for men and women, especially at the state level. IPV may result in adverse health effects for victims and perpetrators (1-3). To estimate the lifetime incidence of IPV by type of violence (e.g., physical, sexual, and perceived emotional abuse) and to explore demographic correlates of reporting IPV among men and women, the South Carolina Department of Health and Environmental Control and the University of South Carolina conducted a population-based random-digit-dialed telephone survey of adults in the state. This report summarizes the results of the survey, which indicated that approximately 25% …

Intimate Partner Violence And Cervical Neoplasia, Ann L. Coker, Maureen Sanderson, Mary Kay Fadden, Lucia Pirisi

CRVAW Faculty Journal Articles

Intimate partner violence (IPV) is associated with a range of adverse physical health outcomes, including chronic and infectious diseases. An emerging literature suggests that partner violence and specifically sexual violence may be associated with an increased risk of cervical neoplasia. To assess the risk of preinvasive and invasive cervical cancer in a cross-sectional study of women screened for IPV by type, frequency and duration, 1152 women ages 18–65 were recruited from family practice clinics in 1997–1998. They were screened for IPV during a brief in-clinic interview, and health history and current status were assessed in a follow-up interview. Of 1152 …

Remifentanil In The Horse: Identification And Detection Of Its Major Urinary Metabolite, A. F. Lehner, P. Almeida, J. Jacobs, J Daniel Harkins, W. Karpiesiuk, W. E. Woods, L. Dirikolu, Jeffrey M Bosken, W. G. Carter, J. Boyles, C. Holtz, T. Heller, C. Nattrass, M. Fisher, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Remifentanil (4-methoxycarbonyl-4-[(1-oxopropyl)phyenylamino]-1- piperidinepropionic acid methyl ester) is a μ-opioid receptor agonist with considerable abuse potential in racing horses. The identification of its major equine urinary metabolite, 4-methoxycarbonyl-4-[(1- oxopropyl)phenylamino]-1-piperidinepropionic acid, an ester hydrolysis product of remifentanil is reported. Administration of remifentanil HCl (5 mg, intravenous) produced clear-cut locomotor responses, establishing the clinical efficacy of this dose. ELISA analysis of postadministration urine samples readily detected fentanyl equivalents in these samples. Mass spectrometric analysis, using solid-phase extraction and trimethylsilyl (TMS) derivatization, showed the urine samples contained parent remifentanil in low concentrations, peaking at 1 h. More significantly, a major peak was identified as …

Exposure To 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (Tcdd) Is Associated With Hyperinsulinemia And Insulin Resistance, Morris Cranmer, Shirley Louie, Richard H. Kennedy, Philip A. Kern, Vivian A. Fonseca

Clinical and Translational Science Faculty Publications

High exposures of Vietnam veterans to 2,3,7,8-Tetrachlorodibenzo-p- dioxin, a dioxin contained in the herbicide mixture Agent Orange, have previously been demonstrated to be associated with an increased prevalence of diabetes and hyperinsulinemia in non-diabetic subjects. Sixty-nine persons were identified who were in good health and had normal glucose levels during glucose tolerance testing. These subjects lived within 25 miles of the Vertac/Hercules Superfund site located in Jacksonville, Arkansas. The blood sera lipid concentrations of TCDD for the 69 subjects ranged between 2 and 94 ppt. When subjects with blood sera lipid TCDD levels in the top 10% (TCDD > 15 ppt, …