Pharmacology, Toxicology and Environmental Health Commons^™

The Metastasis Suppressor Nm23-H1 Is Required For Dna Repair, Mengmeng Yang

University of Kentucky Doctoral Dissertations

NM23-H1 represents the first identified metastasis suppressor, exhibiting reduced expression in breast carcinoma and melanoma, and an ability to inhibit metastatic growth without significant impact on the transformed phenotype. Although its molecular mechanism of action is not fully understood, NM23-H1 possesses at least three enzymatic activities that may mediate metastasis suppressor function. It catalyzes nucleoside diphosphate kinase (NDPK) activity, as well as protein histidine kinase and 3’-5’ exonuclease activities. As 3’-5’ exonucleases are generally required for maintenance of genomic integrity, this activity represents a plausible mediator to underlie the metastasis suppressor function of NM23-H1 protein. To investigate the relevant activity …

Differential Dynamic Properties Of Scleroderma Fibroblasts In Response To Perturbation Of Environmental Stimuli, Xiaodong Zhou

Faculty, Staff and Student Publications

Diseases are believed to arise from dysregulation of biological systems (pathways) perturbed by environmental triggers. Biological systems as a whole are not just the sum of their components, rather ever-changing, complex and dynamic systems over time in response to internal and external perturbation. In the past, biologists have mainly focused on studying either functions of isolated genes or steady-states of small biological pathways. However, it is systems dynamics that play an essential role in giving rise to cellular function/dysfunction which cause diseases, such as growth, differentiation, division and apoptosis. Biological phenomena of the entire organism are not only determined by …

Ecotoxicological Investigations Of Pharmaceutical Compounds On A Battery Of Freshwater Test Species., Elaine Minagh

Masters

Currently interest in pharmaceuticals as potential environmental contaminants has increases significantly. This is due to the awareness of the possible adverse effects to human health and the environment caused by such contaminants. Within the past few years, the highly prescribed antidepressants, selective serotonin reuptake inhibitors (SSRI), have received attention as their occurrence in the environment has been recently documented. Prior to this, there was very little known about the ecotoxicity of SSRIs, and in particular sertraline hydrochloride. Similarly the cholesterol-lowering drugs, known as statins are among the most frequently prescribed agents in Ireland and worldwide for the treatment of coronary …

The Evaluation Of Midazolam On Head Injured Patients In The Prehospital Setting, Dragana Klinac

Theses: Doctorates and Masters

Midazolam (Hypnovel ®) is the only sedating agent used by paramedics at St John Ambulance Service W.A. in the management of many conditions including seizure activities, antisocial or uncontrollable behaviours, back pain incidents and head injuries. Midazolam, with a rapid absorption, fast onset of action and short duration on neurological activity, has been accepted as a safe and effective agent in prehospital treatment since the late-1990s. Often, if a patient is not complying with treatment or is uncontrollable or aggressive, paramedics are required to sedate the individual. This study primarily examines the use of midazolam for the sedation of unmanageable …

Comparison Of Total Mercury And Methylmercury Cycling At Five Sites Using The Small Watershed Approach, James B. Shanley, M. Alisa Mast, Donald H. Campbell, George R. Aiken, David P. Krabbenhoft, Randall J. Hunt, John F. Walker, Paul F. Schuster, Ann Chalmers, Brent T. Aulenbach, Norman E. Peters, Mark Marvin-Dipasquale, David W. Clow, Martin M. Shafer

United States Geological Survey: Staff Publications

The small watershed approach is well-suited but underutilized in mercury research. We applied the small watershed approach to investigate total mercury (THg) and methylmercury (MeHg) dynamics in streamwater at the five diverse forested headwater catchments of the US Geological Survey Water, Energy, and Biogeochemical Budgets (WEBB) program. At all sites, baseflow THg was generally less than 1 ng L^-1 and MeHg was less than 0.2 ng L^-1. THg and MeHg concentrations increased with streamflow, so export was primarily episodic. At three sites, THg and MeHg concentration and export were dominated by the particulate fraction in association with …

Occurrence And Biological Effect Of Exogenous Steroids In The Elkhorn River, Nebraska, Usa, Alan S. Kolok, Daniel D. Snow, Satomi Kohno, Marlo K. Sellin, Louis J. Guillette Jr.

Biology Faculty Publications

Recent studies of surface waters in North America, Japan, and Europe have reported the presence of steroidogenic agents as contaminants. The current study has three objectives: 1) to determine if steroidogenic compounds are present in the Elkhorn River, 2) to determine if sediments collected from the Elkhorn River can act as a source of steroidogenic compounds to aquatic organisms, and 3) to determine if site-specific biological effects are apparent in the hepatic gene expression of fathead minnows. Evidence was obtained using three approaches: 1) deployment of polar organic chemical integrative samplers (POCIS), 2) deployment of caged fathead minnows, and 3) …

Evaluating The Medicinal Properties Of Mandravasarotra (Cinnamosa Sida) Through Chemical And Pharmacological Screening, Henry J. Bowden Jr.

Independent Study Project (ISP) Collection

I worked for four weeks at the University of Antananarivo (Ankatso), spending two weeks each in the chemistry and pharmacology laboratories. There I ran a total of eight experiments or “screens” with an alcoholic extract of the medicinal plant Mandravasarotra. This plant is found mainly in northwestern Madagascar, and is often used to stimulate contractions for women having difficulty giving birth. The plant tested positive for three secondary metabolites: tannins, steroids and flavanoids. In the pharmacological tests, the plant exhibited anti-inflammatory properties, and high toxicity in doses exceeding 10ml/kg. Together, conjectures may be made between what is known of the …

Maternal Serum Polychlorinated Biphenyl Concentrations Across Critical Windows Of Human Development, Michael S. Bloom, Germaine M. Buck-Louis, Aiyi Liu

Environmental Health Sciences Faculty Scholarship

Background

Few data are available on polychlorinated biphenyl (PCB) concentrations over critical windows of human reproduction and development inclusive of the periconception window.

Objectives

Our goal was to measure changes in PCB concentrations from preconception to pregnancy, through pregnancy, or after a year without becoming pregnant.

Methods

Seventy-nine women planning pregnancies were prospectively enrolled and followed for up to 12 menstrual cycles of attempting pregnancy. Blood specimens were obtained from participating women preconceptionally (n = 79), after a positive pregnancy test leading to a live birth (n = 54) or pregnancy loss (n= 10), at approximately …

Lead-Contaminated Candies In Southern Nevada, Shawn Gerstenberger, Glenn Savage, Clayton Sellers, Keith Zupnik, Emmanuel C. Gorospe

Environmental & Global Health Faculty Research

Lead-contaminated candies from Latin America are beginning to gain attention in the public media1,2 and in the medical literature.3–5 These candies come from a number of sources and are manufactured outside Food and Drug Administration regulatory control. In 2005, we sampled 50 imported Latin American candies sold in Southern Nevada. A total of 20 (40%) tested positive with an average lead content of 1.46  0.27 mg/kg in the candies’ wrappers and straws, based on standard Graphite Furnace Atomic Absorption Spectrophotometry methodology. Given these results, the Southern Nevada Health District issued a cease-and-desist order on February 13, 2006, to local …

Post Hoc Pattern Matching: Assigning Significance To Statistically Defined Expression Patterns In Single Channel Microarray Data, Randall Hulshizer, Eric M. Blalock

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Researchers using RNA expression microarrays in experimental designs with more than two treatment groups often identify statistically significant genes with ANOVA approaches. However, the ANOVA test does not discriminate which of the multiple treatment groups differ from one another. Thus, post hoc tests, such as linear contrasts, template correlations, and pairwise comparisons are used. Linear contrasts and template correlations work extremely well, especially when the researcher has a priori information pointing to a particular pattern/template among the different treatment groups. Further, all pairwise comparisons can be used to identify particular, treatment group-dependent patterns of gene expression. However, these approaches …

Layer -By -Layer Self -Assembly Of Micro-Capsules For The Magnetic Activation Of Semi-Permeable Nano-Shells, Malcolm D. Prouty

Doctoral Dissertations

Layer-by-layer (LbL) self-assembly has demonstrated broad perspectives for encapsulating, and the controllable delivery, of drugs. The nano-scale polymer layers have the capability of material protection. Magnetic nanoparticles have great potential to be applied with LbL technology to achieve both "focusing" of the encapsulated drugs to a specific location followed by "switching" them on to release the encapsulated drugs. In this work, Phor21-βCG(ala), dextran, and dexamethasone were used as model drugs. Encapsulation of these drugs with layer-by-layer self-assembly formed biolnano robotic capsules for controlled delivery and drug release.

Silica nanoparticles coated with polyelectrolyte layers of sodium carboxymethyl cellulose (CMC) or gelatin …

Maturational Changes In Cerebrovascular Thick- And Thin-Filament Regulation, Renan Joel Sandoval

Loma Linda University Electronic Theses, Dissertations & Projects

The present study focused on the main hypothesis that age-related changes in myofilament Ca²⁺ sensitivity involve simultaneous changes in the relations between cytosolic Ca²⁺ transients, myosin phosphorylation, and force development. To define the effects of late fetal and early postnatal maturation, parallel experiments were carried out using cerebral arteries from both term lamb fetuses (140-141 days of gestation) and nonpregnant adult sheep. Fetal and adult cerebral arteries were stimulated by either mechanically, electromechanically, and/or pharmacomechanically-induced contractions, and the relations of cytosolic Ca²⁺, MLC phosphorylation, and contractile tensions were measured. These measurements allowed for stimulus and age-dependent …

Immunoadjuvanticity Of Chlorophyll, Jocelyn Helen Parks Ramos

All-Inclusive List of Electronic Theses and Dissertations

Background: Vaccines are formulations containing antigenic determinants (from non-self organic matters) and immuno-enhancers called adjuvants. Together, they evoke protective immune responses in hosts. Adjuvants are substances that further vaccines' capability to induce a robust immune response. Common side effects with conventional adjuvants used in most vaccines are toxicity, inflammation and granulomas. In this study we investigated the pigment chlorophyll (Chl) for immunoadjuvanticity. The selection of chlorophyll is based on the fact that it is a component in foods such as spinach, and that it contains an isoprenoid structure that is a feature of many conventional adjuvants, Pristane and Squalene. Chl …

Regulation Of Alpha-1-Adrenoceptor-Mediated Contractions Of The Uterine Artery By Pkc, Hongying Zhang

Loma Linda University Electronic Theses, Dissertations & Projects

Pregnancy is associated with a significant decrease in uterine vascular tone and a striking increase in uterine blood flow, which ensures normal fetal development. Multiple mechanisms are involved in the adaptation of uterine artery contractility during pregnancy. Both protein kinase C (PKC) and activation of ai-adrenoceptors play important roles in the regulation of uterine artery contractility. In addition, PKC mediates the pregnancyassociated decrease in myogenic tone of the uterine artery, and interacts with ajadrenoceptors leading to modulation of ai-adrenoceptor-mediated contractions of vascular smooth muscle. Yet, whether or to what extent PKC regulates ai-adrenoceptormediated contractions of the uterine artery and their …

Expansion Of The Calcium Hypothesis Of Brain Aging And Alzheimer's Disease: Minding The Store, Olivier Thibault, John C. Gant, Philip W. Landfield

Pharmacology and Nutritional Sciences Faculty Publications

Evidence accumulated over more than two decades has implicated Ca2+ dysregulation in brain aging and Alzheimer's disease (AD), giving rise to the Ca2+ hypothesis of brain aging and dementia. Electrophysiological, imaging, and behavioral studies in hippocampal or cortical neurons of rodents and rabbits have revealed aging-related increases in the slow afterhyperpolarization, Ca2+ spikes and currents, Ca2+transients, and L-type voltage-gated Ca2+ channel (L-VGCC) activity. Several of these changes have been associated with age-related deficits in learning or memory. Consequently, one version of the Ca2+ hypothesis has been that increased L-VGCC activity drives many of the other Ca2+-related biomarkers of hippocampal aging. …

The Economics Of Water Utilization: Tools And Applications, Matt Bogard

Agriculture Department Seminar Series

Given worldwide problems of access to safe potable water, this presentation examines how tools of economics can aid in drafting appropriate mitigating policies. Utilizing partial equilibrium analysis, it demonstrates the role that prices play in social coordination and then applies the framework to real world examples. In addition it examines Pigouvian Taxation and Coasean Bargaining as two classic methods for dealing with externalities in the context of water pollution. Second-best solutions such as tradable permits and metered pricing by public utilities are discussed. This presentation concludes by examining the issues and challenges that policy makers face when trying to implement …

The History Of Thalidomide, Ilana Fakherian

The Science Journal of the Lander College of Arts and Sciences

Thalidomide, introduced in Germany in 1954, was a drug that was initially prescribed for its sedative properties. In the late 1950s, thalidomide was widely used by women as an antiemetic drug to alleviate the nausea and vomiting (morning sickness) common in the early stages of pregnancy and to help them sleep. Thalidomide gained notoriety in 1961 when it was found to cause severe malformations in the growing fetus, such as stunted development or the complete absence of limbs. More over, later studies revealed that thalidomide generates peripheral neuropathy, dizziness, constipation, and menstruation abnormalities. However, at the time, inadequate tests were …

Drug Loading And Release From Polypeptide Multilayer Nanofilms, Yang Zhong

Doctoral Dissertations

Polypeptides, linear macromolecules, are formed from amino acid residues by linkage of peptide bonds. Proteins are polypeptides too, with more complex conformations contributing to specific functionalities. Disulfide bonds are very important to maintain the structure and functions of proteins, which will form between two cysteine (Cys) residues under oxidizing circumstance.

Cys containing polypeptides are designed and synthesized by F-moc (9-Fluorenylmethyloxycarbonyl) chemistry. The number and position of Cys residues can be controlled by amino acid sequences design and following peptide synthesis, which is important to gain insights on the nature of polyelectrolyte multilayer film assembly and stability.

Both commercial and designed …

Nonylphenol Stimulates Fecundity But Not Population Growth Rate (Λ) Of Folsomia Candida, T. H. Widarto, P. H. Krogh, Valery E. Forbes

Valery Forbes Publications

The toxicity of nonylphenol (NP) to springtails was pronounced at 40 mg/kg dry weight soil, at which no animals survived. Body length and fecundity were the individual life-history traits significantly stimulated by sublethal concentrations of NP during a 64-day experiment. However, the effects of NP on these traits did not result in a statistically significant increase in population growth rate (λ). Decomposition analysis indicated that fecundity was the main contributor to the (non-significant) changes observed in λ. However, since the elasticity of fecundity was very low, large changes in fecundity resulted in a minimal effect on λ. Juvenile survival had …

Does Bisphenol A Induce Superfeminization In Marisa Cornuarietis? Part Ii: Toxicity Test Results And Requirements For Statistical Power Analyses, Valery E. Forbes, John Aufderheide, Ryan Warbritton, Nelly Van Der Hoeven, Norbert Caspers

Valery Forbes Publications

This study presents results of the effects of bisphenol A (BPA) on adult egg production, egg hatchability, egg development rates and juvenile growth rates in the freshwater gastropod, Marisa cornuarietis. We observed no adult mortality, substantial inter-snail variability in reproductive output, and no effects of BPA on reproduction during 12 weeks of exposure to 0, 0.1, 1.0, 16, 160 or 640 μg/L BPA. We observed no effects of BPA on egg hatchability or timing of egg hatching. Juveniles showed good growth in the control and all treatments, and there were no significant effects of BPA on this endpoint. Our …

Does Bisphenol A Induce Superfeminization In Marisa Cornuarietis? Part I: Intra- And Inter-Laboratory Variability In Test Endpoints, Valery E. Forbes, Henriette Selck, Annemette Palmqvist, John Aufderheide, Ryan Warbritton, Nadine Pounds, Roy Thompson, Norbert Caspers

Valery Forbes Publications

It has been claimed that bisphenol A (BPA) induces superfeminization in the freshwater gastropod, Marisa cornuarietis. To explore the reproducibility of prior work, here we present results from a three-laboratory study, the objectives of which were to determine the mean and variability in test endpoints (i.e., adult fecundity, egg hatchability, and juvenile growth) under baseline conditions and to identify the sources of variability. A major source of variability for all of the measured endpoints was due to differences within and among individuals. With few exceptions, variability among laboratories and among replicate tanks within laboratories contributed little to the observed variability …

Conceptual Model For Improving The Link Between Exposure And Effects In The Aquatic Risk Assessment Of Pesticides, J. J.T.I. Boesten, H. Köpp, P. I. Adriaanse, T. C.M. Brock, Valery E. Forbes

Valery Forbes Publications

Assessment of risks to aquatic organisms is important in the registration procedures for pesticides in industrialized countries. This risk assessment consists of two parts: (i) assessment of effects to these organisms derived from ecotoxicological experiments (= effect assessment), and (ii) assessment of concentration levels in relevant environmental compartments resulting from pesticide application (= exposure assessment). Current procedures lack a clear conceptual basis for the interface between the effect and exposure assessments which may lead to a low overall scientific quality of the risk assessment. This interface is defined here as the type of concentration that gives the best correlation to …

The Status Of Childhood Lead Poisoning And Prevention In Nevada, Usa, Anne Rothweiler, Elena E. Cabb, Shawn Gerstenberger

Environmental & Global Health Faculty Research

One of the first steps in addressing the problem of childhood lead poisoning is to identify the possible sources of exposure in specific communities and target high-risk populations with appropriate interventions. Due to several factors, such as lack of funding and lack of blood lead reporting, little information exists regarding the occurrence of childhood lead poisoning and the prevalence of potential exposure sources in the state of Nevada. Following the recent establishment of a Nevada-based Lead Poisoning Program, we compiled the most current information available on Nevadans, and use this knowledge to suggest future research objectives and outreach activities for …

Chemometrics-Assisted Spectrophotometric Determination Of Certain Β-Lactam Antibiotics Combinations, Abd El-Maboud I. Mohamed, Hesham Salem, Eman Maher

The Thai Journal of Pharmaceutical Sciences

Multivariate and derivative spectrophotometric techniques (first derivative and derivative ratio) were developed for the determination of four p-lactam antibiotic binary mixtures; ampicillin with flucloxacillin (mix I), ampicillin with dicloxacillin (mix...

Effects Of Drying Temperature And Residual Moisture Content Of Fa-Tha-Li (Andrographis Paniculata (Burm.F.) Nees) Crude Powder For Capsule Preparation, Wipawee Saohin, Preecha Boonchoong, Supachai Lamlikitkuakoon, Itthichai Jamnoiprom, Wittaya Mungdee

The Thai Journal of Pharmaceutical Sciences

The objectives of this research were to study the effects of drying temperature and residual moisture content on total lactones content calculated as andrographolide, flow ability and microbial contamination of Fa-Tha-Li (Andrographis paniculata (Burm.f....

Characterization Of Herpes Simplex Virus Type 1 Selected In Culture For Resistance To Acyclovir Or Foscarnet, Mali Wirotesangthong, Sakulrat Rattanakiat, Katsuhiko Matsui, Vimolmas Lipipun

The Thai Journal of Pharmaceutical Sciences

To determine the characteristics of herpes simplex virus type 1 (HSV-1) resistant to either acyclovir (ACV) or foscarnet (FOS), HSV-1 KOS (wild-type) strain was used for selection of drug-resistant mutants in Vero cells. เท one-step growth curve, all...

An Approach To Developing Dissolution Standards For Turmeric Capsules I: Basket Rotating Method, Nantana Sittichai, Sirichai Krabesri, Ekamol Suthison, Parkpoom Tengamnuay

The Thai Journal of Pharmaceutical Sciences

A simple dissolution test and standard was developed for Turmeric capsules to replace the less discriminating disintegration test stated in the Supplement to Thai Herbal Pharmacopoeia 2004. The proposed test used the basket at 100 rpm and the dissolution...

Comparative Analysis Of Pharmaceutical Care And Traditional Dispensing Role Of Pharmacy, Phantipa Sakthong

The Thai Journal of Pharmaceutical Sciences

Pharmaceutical care is a new professional practice that can give an opportunity to pharmacists to prove themselves as a real health care profession. Pharmaceutical care practitioners are concerned with the outcomes of their services on patients’ life a...

Use Of A Dialyzable Short-Chain Phospholipid For Efficient Preparation Of Virosome Vaccines Against Newcastle Disease, Atthachai Homhuan, Sompol Prakongpan

The Thai Journal of Pharmaceutical Sciences

Virosomes can be regarded as liposomes carrying the spike proteins of enveloped virus on their surface. To further advance the use of virosomes, we developed a solubilization/ reconstitution procedure for construction of Newcastle disease (ND)-virosomes,...

28-Day Repeated Dose Oral Toxicity Study Of Litsea Cubeba Essential Oil In Sprague-Dawley Rats, Siraprapa Tubtim, Ake Wasiksiri

The Thai Journal of Pharmaceutical Sciences

Litsea cubeba essential oil is a raw material source for the isolation of citral that can be converted to a number of important derivatives. This citral-rich essential oil is also increasingly used for flavour and fragrance applications in many household...