Pharmacology, Toxicology and Environmental Health Commons^™

Application Of A Stability-Indicating Hptlc Method For Simultaneous Determination Of Chloramphenicol And Dexamethasone Sodium Phosphate In Eye Drop, Yimer Seid, Araya Hymete, Adnan A. Bekhit

The Thai Journal of Pharmaceutical Sciences

A high performance thin layer chromatography (HPTLC) method was developed and validated for the simultaneous quantification of dexamethasone sodium phosphate and chloramphenicol in eye drop. The HPTLC separation was achieved on an aluminum-backed layer of silica gel 60F254 using acetonitrile: water: ammonia (10:3:0.5 v/v/v), pH adjusted to 7.8 with 1M HCl, as a mobile phase. The densitometric determination of dexamethasone phosphate and chloramphenicol was carried out at 262 nm. Calibration curves for dexamethasone phosphate and chloramphenicol were linear in the range of 80-300 ng and 400-1400 ng, respectively. The method was validated according to International Conference on Harmonization (ICH) guidelines …

Enhancement Of Wttability And In Vitro Dissoution Properties Of Lercanidipine Hydrochloride By Solid Dispersion Technique, Suneel Pandey, Ekunkumar Chandekar, Amarnath Wattamwar, Sachin Pandit, Hemant Joshee, Arun Patil

The Thai Journal of Pharmaceutical Sciences

The aim of the present study was to improve lercanidipine HCl solubility and in vitro dissolution rate by preparing solid dispersion with polyethylene glycol (PEG) 6000 using the solvent evaporation technique. Solid dispersions with PEG 6000 (as carriers) were prepared in drug: carrier (1:1, 1:5 and 1:10) ratios along with the corresponding physical mixtures. Analytical techniques, FT-IR spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to characterize the drug in the physical mixtures and solid dispersions. The solubility and wettability studies of solid dispersions as well as physical mixtures showed greater improvement compared to the pure drug. …

Associations Between Serum Concentrations Of Polychlorinated Biphenyls, Serum Carotenoids, And The Probability Of Metabolic Syndrome In The National Health And Nutrition Examination Survey 2003-2004, Carolyn R. Hofe

Theses and Dissertations--Nutritional Sciences

Diabetes and cardiovascular disease are leading causes of death and disability in the United States. These chronic diseases are clinical sequelae of metabolic syndrome (MetS), a condition that affects approximately one-third (1/3) of American adults. Metabolic syndrome occurs in response to environmental and genetic influences, among them food intake, a sedentary lifestyle, BMI, advancing age, and exposure to persistent organic pollutants (POPs). POPs are known to cause endocrine disruption and PCBs cause oxidative stress, disrupt endothelial cell integrity, and promote atherosclerosis. Nutrition plays a significant role in the prevention and management of these chronic diseases and has been shown to …

Combretazet-3 A Novel Synthetic Cis-Stable Combretastatin-A4-Azetidinone Hybrid With Enhanced Stabilityand Therapeutic Efficacy In Colon Cancer, Lisa M. Greene, Shu Wang, Niamh O'Boyle, Sandra A. Bright, Jane E. Reid, Patrick Kelly, Mary J. Meegan, Daniela M. Zisterer

Articles

In recent years an extensive series of synthetic combretastatin A-4 (CA-4)-azetidinone (β-lactam) hybrids were designed and synthesised with a view to improve the stability, therapeutic efficacy and aqueous solubility of CA-4. Lead compounds containing a 3,4,5-trimethoxy aromatic ring at position 1 and a variety of substitution patterns at positions 3 and 4 of the β-lactam ring were screened in three adenocarcinoma-derived colon cancer cell lines (CT-26, Caco-2 and the CA-4 resistant cell line, HT-29). In both CT-26 and Caco-2 cells all β-lactam analogues analysed displayed potent therapeutic efficacy within the nanomolar range. Substitution of the ethylene bridge of CA-4 with …

Cationic Amphiphilic Drug-Induced Autophagosome Accumulation Is Due To Autophagosome Sequestration Within Vimentin Intermediate Filament Networks Resulting In Prolonged Autophagosome Half-Life, Miriam Devorah Kleinman

Wayne State University Dissertations

Accumulations of autophagosomes and non-esterified cholesterol are

observed in several cell lines derived from lysosomal storage diseases,

including Niemann Pick Type C (NPC). The relationship between

autophagosome accumulation and lysosomal non-esterified cholesterol is

unclear. Exposure of murine hepatoma 1c1c7 cultures to the cationic

amphiphilic drugs (CADs) U18666A, imipramine and clozapine caused

lysosomal non-esterified cholesterol and autophagosome accumulation.

Measurement of LC3-II conversion in the presence of lysosomal inhibitors

bafilomycin A1 and NH4Cl, degradation of long-lived proteins, and

colocalization of GFP-LC3 and LAMP1 indicated an increase in

autophagosome synthesis without compensatory increase in clearance.

Autophagosome synthesis was blocked using 3-MA to monitor …

Short-Term Associations Between Pm2.5, Black Carbon, Delta-C, And Cardiovascular Diseases In A Large Developing Megacity, Daniel Malashock

Legacy Theses & Dissertations (2009 - 2024)

Introduction: Association between ambient air pollution and cardiovascular disease (CVD) have been demonstrated by many epidemiological studies in developed countries, however few studies have been performed in developing countries of Asia.

Trace Element Analysis Of Environmental And Clinical Materials Using Novel Instrumentation Based On X-Ray Fluorescence Spectrometry : New Capabilities For Public Health Laboratories, Kathryn G. Mcintosh

Legacy Theses & Dissertations (2009 - 2024)

X-ray fluorescence (XRF) spectrometry is a well-established analytical technique for determining the elemental content of many different materials. XRF has long been used for public health applications, particularly for identifying lead-based paint hazards. The primary advantage of XRF over other atomic spectrometric techniques is that it is nondestructive. In addition, little sample preparation is required, so results are obtained rapidly and at low cost. The principal aim of this study was to characterize the utility and reliability of current XRF instrumentation for use in the environmental health sciences. Interest in the use of XRF for detecting lead in children's toys …

Occupational Exposure And Risk Of Skin Cancer In A Multinational European Study, Simona Surdu

Legacy Theses & Dissertations (2009 - 2024)

Non-melanoma skin cancers (NMSC) comprise more than one third of all cancers, and are increasing worldwide. The most common NMSC are Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC). Studies on humans and animals suggest that sunlight and arsenic play important roles in the pathogenesis of these skin malignancies. However, the number of epidemiological studies focusing on NMSC in workers exposed to ultraviolet (UV) radiation or airborne arsenic is limited, and the findings are contradictory.

Association Between Chemical Constituents Of Particulate Matter And Cardiovascular And Respiratory Morbidities In Nys, Rena Jones

Legacy Theses & Dissertations (2009 - 2024)

Improved understanding of health risks from short- and long-term exposure to fine particulate matter (PM_2.5) constituents may explain seasonal and geographic heterogeneity in PM_{2.5-health associations and inform control efforts targeting PM sources. Few studies have examined PM species health effects; most have been limited by their exposure assessments and modeling approaches. The goals of this project were to improve the PM exposure assessment and explore relationships between PM2.5 species and health in acute and chronic contexts.}

Evaluation Of The Short- And Long- Term Drinking Water Sustainability Programs For Point Water Sources And Public Water Supplies (Pws) In Developing Countries : Case Study Of Uganda, Shedrack R. Nayebare

Legacy Theses & Dissertations (2009 - 2024)

Providing quantity and quality potable water in Uganda and other developing countries is still significantly problematic. This project aimed at identifying and prioritizing possible actions on how sustainable and high quality potable water in Uganda's water supply systems could be improved. A review of both the current water supply systems and Ugandan government programs was completed in an effort to describe the existing state of Uganda's water supply. Aspects of quantity, quality, treatment methods, infrastructure, storage and distribution of water for the different water systems were assessed. These characteristics were compared to water supply systems and regulations in the U.S., …

Seafood Consumption And Use Of Asian Herbal Preparation As A Source Of Exposure To Multiple Trace Elements In The Study Of Metals And Assisted Reproductive Technologies (Smart), Dongsul Kim

Legacy Theses & Dissertations (2009 - 2024)

As, Cd, Cs, Hg, Pb, and Zn may be associated with in vitro fertilization (IVF) outcomes. Seafood and Asian herbal preparations are identified as sources of exposure to these essential and non-essential trace elements in humans. The goal of the study is to assess associations between seafood consumption and the use of Asian herbal preparations and levels of essential and non-essential trace elements in biologic specimens collected from couples undergoing IVF. Fifty-nine couples completing a first IVF cycle at the University of California, San Francisco (UCSF) Center for Reproductive Health were recruited to participate in the Study of Metals and …

A Thousand Tiny Pieces: The Federal Circuit’S Fractured Myriad Ruling, Lessons To Be Learned, And The Way Forward, Jonathan R. K. Stroud

IP Theory

No abstract provided.

Effects Of Partner Proteins On Bca2 Ring Ligase Activity, Stephanie Bacopulos, Yutaka Amemiya, Wenyi Yang, Judit Zubovits, Angelika Burger, Martin Yaffe, Arun K. Seth

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

BCA2 is an E3 ligase linked with hormone responsive breast cancers. We have demonstrated previously that the RING E3 ligase BCA2 has autoubiquitination activity and is a very unstable protein. Previously, only Rab7, tetherin, ubiquitin and UBC9 were known to directly interact with BCA2.

Methods

Here, additional BCA2 binding proteins were found using yeast two-hybrid and bacterial-II-hybrid screening techniques with Human breast and HeLa cDNA libraries. Co-expression of these proteins was analyzed through IHC of TMAs. Investigation of the molecular interactions and effects were examined through a series of in vivo and in vitro assays.

Results

Ten unique …

Novel Inhibitors Of The Bacterial De Novo Purine Biosynthesis Enzymes, N5-Carboxyaminoimidazole Ribonucleotide Synthetase And Mutase, Maria V. Fawaz

Wayne State University Theses

Antibiotic resistance has seen a significant increase during the past decade. The increasing frequency of the drug-resistant bacterial infections has amplified the need for novel antimicrobial agents. De novo purine biosynthesis is one area that has great potential for antibacterial drug development because this pathway is different in microorganisms versus humans. The difference in the pathway is centered on the synthesis and utilization of the purine intermediate N⁵-carboxy-5-aminoimidazole ribonucleotide (N⁵-CAIR). Previous studies have shown that N⁵-CAIR is a key intermediate in purine biosynthesis in bacteria, yeast and fungi, but not in humans. N^{5 …}

The Effect Of Cadmium Exposure On Repeat Swimming Performance And Recovery In Rainbow Trout (Oncorhynchus Mykiss), Brown Trout (Salmo Trutta) And Lake Whitefish (Coregonus Clupeaformis), Jessie L. Cunningham

Theses and Dissertations (Comprehensive)

Swim performance provides a measure of the integrated metabolic costs of sub-lethal exposure to stressors, including Cd. While the impacts to sustained swimming performance in Cd exposed fish have already been characterised, effects to repeat swimming ability have not. This thesis identifies the effects of sub-lethal waterborne Cd exposure on ionoregulatory function, repeat swimming ability, anaerobic metabolism and stress response in rainbow trout (Oncorhynchus mykiss), brown trout (Salmo trutta) and lake whitefish (Coregonus clupeaformis).

Repeat swim trials included an initial swim to 85% of the U_crit of control fish and a recovery period …

Vascular Kv7 (Kcnq) Potassium Channels As Therapeutic Targets In Cerebral Vasospasm, Bharath Kumar Mani

Dissertations (6 month embargo)

Cerebral vasospasm, a grave sequel to subarachnoid hemorrhage (SAH), is characterized by prolonged severe constriction of arteries in the base of the brain, including the basilar artery. Spasmogens (serotonin, endothelin and vasopressin), elevated in response to SAH, induce persistent depolarization of the myocytes in the artery wall, leading to continuous influx of calcium (Ca2+) through voltage-sensitive Ca2+ channels (VSCC) resulting in hyperconstriction (spasm). The spasm of the arteries restricts blood flow to the brain, inducing ischemic neurological deficits and consequential high morbidity and mortality. The cellular pathogenesis of cerebral vasospasm is poorly understood and the therapeutic options are limited.

Kv7 …

Sterol Lipid Metabolism In Down Syndrome Revisited: Down Syndrome Is Associated With A Selective Reduction In Serum Brassicasterol Levels, Gavin Tansley, Daniel T. Holmes, Dieter Lütjohann, Elizabeth Head, Cheryl L. Wellington

Pharmacology and Nutritional Sciences Faculty Publications

Over the past 15 years, insights into sterol metabolism have improved our understanding of the relationship between lipids and common conditions such as atherosclerosis and Alzheimer's Disease (AD). A better understanding of sterol lipid metabolism in individuals with Down Syndrome (DS) may help elucidate how this population's unique metabolic characteristics influence their risks for atherosclerosis and AD. To revisit the question of whether sterol lipid parameters may be altered in DS subjects, we performed a pilot study to assess traditional serum sterol lipids and lipoproteins, as well as markers of sterol biosynthesis, metabolites, and plant sterols in 20 subjects with …

Aging And Down Syndrome, Elizabeth Head, Wayne Silverman, David Patterson, Ira T. Lott

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Targeting Α4 Integrin Containing Complexes In Multiple Myeloma Using Peptidomimetics, Michael Foster Emmons

USF Tampa Graduate Theses and Dissertations

In our previous work we demonstrated that the integrin antagonist, HYD1, induced necrotic cell death in myeloma cell lines in vitro and in vivo as a single agent. In order to further delineate biomarkers of response to HYD1 we developed an isogenic drug resistant variant named H929-60. We show that the acquisition of resistance towards HYD1 correlates with reduced expression of the cleaved α4 integrin subunit and beta 1 integrin. Moreover, we demonstrate that HYD1 interacts with α4 integrin in myeloma cells. Consistent with reduced VLA-4 expression, the resistant variant showed ablated functional binding to fibronectin, VCAM-1 and the bone …

Use And Development Of Computational Tools In Drug Discovery: From Small Molecules To Cyclic Peptides, Daniel Navarrete Santiago

USF Tampa Graduate Theses and Dissertations

The scope of this work focuses on computationally modeling compounds with protein structures. While the impetus of drug discovery is the innovation of new therapeutic molecules, it also involves distinguishing molecules that would not be an effective drug. This can be achieved by inventing new tools or by refining old tools. Virtual screening (VS, also called docking), the computational modeling of a molecule in a receptor structure, is a staple in predicting a molecule's affinity for an intended target. In our Virtual Target Screening system (also called inverse-docking), VS is used to find high-affinity targets, which can potentially explain absorption, …

Full Issue: Volume 5, Issue 2

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

Full Issue: Volume 6, Number 1

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

Skin Irritation Study Of Two Patented Mix Extracts From Emblica, Ma-Khwaen And Khanun, Sareeya Reungpatthanaphong, Tuanta Sematong, Buppachart Potduang, Phanukit Kunhachan, Cholticha Niwaspragrit

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Moisturizing Gel Formulation Containing Pueraria Mirifica Extracts As An Anti-Wrinkle Agent, Thanachod Thammachat, Sompoch Tubcharoen, Sitthiphong Soradech, Somnuk Promdang

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Role Of Na+K+2cl- Co-Transporters In Insulin Secretion, Saeed Alshahrani

Browse all Theses and Dissertations

The objective of this study is to investigate the role of intracellular chloride concentration ([Cl^-]i) in insulin secretion in vivo and in vitro.

The maintenance of high [Cl^-]i in insulin-secreting pancreatic β-cells plays an important role in glucose-induced depolarization and insulin secretion. Insulinotropic glucose concentrations i.e., >6 mM induces electrical activity in β-cells which results in insulin secretion. This electrical activity is mainly due to electrogenic efflux of Cl^- from β-cells through volume-regulated anion channels (VRAC). The solute carrier family 12 group A member 1 (Slc12a1) and 2 (Slc12a2) encode several splice variants of the …

Investigation Of The Absorptive Potential Of Polymeric Nanoparticles Across The Lungs And Their Development For Efficient Systemic Delivery Following Pulmonary Administration, Abdul Khader Mohammad

Wayne State University Dissertations

The lungs are an attractive route for drug delivery due to their high epithelial surface area available for absorption, a thin epithelium and extensive vasculature to name a few. Accordingly, a vast number of small molecule drugs, peptides, and proteins have been used to investigate their translocation across the lungs with many of the tested candidates showing excellent pharmacokinetics following pulmonary administration. Findings from all these studies over the years have strongly established the lungs as a route for drug delivery of small molecules and proteins. Nanoparticles on the other hand have gained increasing interest in drug delivery due to …

Multifunctional Bioreducible Nanoparticles For Gene Therapy, Jing Li

Wayne State University Dissertations

Gene therapy is a promising therapeutic strategy to treat diseases caused by single or multiple gene mutations. Non-viral gene delivery vectors exhibit many advantages over viral vectors, including enhanced safety, versatility in choosing different types of therapeutic nucleic acids, and ease of formulation. However, low transgene efficiency and lack of targeting ability remain major challenges. Bioreducible polyplexes (polyelectrolyte complexes of disulfide-containing polycations and nucleic acids) utilize the redox potential gradient existing between extracellular space and intracellular environment as a physiological stimulus to enhance delivery of therapeutic nucleic acids to the subcellular space. Bioreducible containing polyplexes undergo intracellular reduction mediated GSH, …

Valproic Acid-Induced Teratogenesis In Japanese Rice Fish (Oryzias Latipes) Embryogenesis, Mengmeng Wu

Electronic Theses and Dissertations

Valproic acid (VPA) was introduced as an antiepileptic in 1967 in France and it has become the most prescribed anticonvulsive drug therapy worldwide since then. In the clinic, valproic acid is selected to treat absence seizures, myoclonic seizures, generalized tonic-clonic seizures, atonic attacks and partial seizures. Epilepsy is the second most comneurologic disorder that affects pregnant women (0.5%–1%). Approximately 1 out of 250 pregnant women are taking antiepileptic drugs. Valproic acid is designated as a human teratogen, which induces major congenital anomalies, facial dysmorphic features, and autistic-like behaviors, which affect verbal, cognitive, communicative, and social abilities of affected children. We …

Elucidating Transcription Factor Regulation By Tcdd Within The Hs1,2 Enhancer, Sharon D. Ochs

Browse all Theses and Dissertations

Immunoglobulin heavy chain (IgH) expression and Ig secretion is inhibited by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD). Within the IgH gene, the 3' IgH regulatory region (3'IgH RR) has been identified as a transcriptional target of TCDD. The 3'IgH RR, which in part regulates transcription of the IgH gene, is composed of four enhancers in the mouse: hs3a; hs1,2; h3b; hs4 and three enhancers in the human: hs3a; hs1,2; hs4. In humans the hs1,2 enhancer has an invariant sequence (IS) containing a DRE, NF-κB, NF1 and AP-1 binding site. Also, the enhancer has an AP1.ETS and Oct …

Evaluation Of Cm-2,525 As A Neuroprotectant Against Sarin: A Comparison With 8-Oh-Dpat, Amanda R. Furman

Browse all Theses and Dissertations

Exposure to the chemical warfare agent sarin produces long term neurological deficits. The long term medical consequences could be averted with the development of neuroprotectants to preserve brain function. In our mouse model, the combination of the carboxylesterase inhibitor 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP) with the organophosphorus (OP) nerve agent sarin was used to render mice more sensitive to poisoning and reduce the amount of hydrogen fluoride cleaved from sarin during binding to esterases. Since carboxylesterase acts as a scavenger, reducing the levels causes sarin to have a greater inhibition effect on acetylcholinesterase. These smaller doses permitted the use of doses similar to …