Pharmacology, Toxicology and Environmental Health Commons^™

Species - Dependent Cardiac And Motor Responses To Cholinergic Stimulation In Daphnia Pulex And Daphnia Magna, Bryan James Hannan

Wayne State University Theses

The role of acetylcholine (ACh) in regulating the activity of the heart and `feeding current' driven by the beating thoracic appendages of Daphnia pulex and Daphnia magna was evaluated using acetylcholinesterase inhibitors (AChE-I) and muscarinic receptor agonists. Single animals, tethered to a stainless steel pin, were tested in a watertight aquatic chamber that allowed free movement of appendages and swimming antennae. Heart contraction rate and the rate of thoracic appendage beating were quantified optically by measuring fluctuating changes in light-intensity caused by movement. Physostigmine, neostigmine, oxotremorine, pilocarpine as well as nicotine were used to study ACh and AChE. Atropine was …

Development And Evaluation Of Plga-S-S-Peg Micelles Coencapsulating Curcumin Difluorinated And Paclitaxel For Synergistic Therapeutic Efficacy, Lakshmi Deepika Cheemalakonda

Wayne State University Theses

ABSTRACT

DEVELOPMENT AND EVALUATION OF PLGA-S-S-PEG MICELLES COENCAPSULATING CURCUMIN DIFLUORINATED AND PACLITAXEL FOR SYNERGISTIC THERAPEUTIC EFFICACY

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LAKSHMI DEEPIKA CHEEMALAKONDA

August 2014

Advisor: Dr. Joshua Reineke Major: Pharmaceutical Sciences Degree: Master of Science

Solid tumors like pancreatic tumor has unique property of forming a dense desmoplastic layer around the tumor cells making it difficult for the drug to transport across this layer. Multi drug resistance is also one of the major limitation of chemotherapy. Therefore the aim of this project was to make PLGA-SS-PEG micelles encapsulating CDF and paclitaxel for synergistic cancer therapy. CDF was found to have 16-fold better …

Site-Directed Mutagenesis Of Conserved Amino Acids Residues In N5-Carboxyaminoimidazole Ribonucleotide Mutase: Converting N5-Cair Mutase Into Aminoimidazole Ribonnucleotide Carboxylase & Developing A High-Throughput Screening Assay For The Discovery Of N5-Carboxyaminoimidazole Ribonucleotide Mutase, Zhiwen Shi

Wayne State University Theses

The de novo purine biosynthesis pathway plays a critical role in providing new purines to the cell. Previous studies have shown differences between the human and bacterial pathways which suggests that pathway may be a potential target for antibiotic drug discovery. Three critical enzymes are involved in the pathway divergence. In the bacterial pathway, N5-CAIR synthetase (PurK) first converts AIR to N5-CAIR, which is then transformed into CAIR catalyzed by the enzyme N5-CAIR mutase (Class I PurE). In the human pathway, AIR carboxylase (Class II PurE) catalyzes the direct conversion of AIR to CAIR. Class I and Class II PurEs …

Functional Studies Of 5-Carboxyaminoimidazole Ribonucleotide Synthetase And Mutase From Thermotoga Maritima, Mingyang Zhao

Wayne State University Theses

De novo purine biosynthesis is divergent depending upon the organism. In bacteria, yeasts and plants, 5-aminoimidazole ribonucleotide (AIR) is converted to 4-carboxyaminoimidazole ribonucleotide (CAIR) by N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) synthetase (PurK) and N5-CAIR mutase (Class I PurE). In animals, AIR is converted into CAIR by AIR carboxylase (Class II PurE). The distinction makes PurK and Class I PurE good targets in design of antimicrobial drugs. N5-CAIR is chemically unstable with t1/2 of about 0.9 minutes at pH 7.8 and 37 °C. If the production of N5-CAIR is not regulated relative to its conversion to CAIR, ATP utilization can rapidly become non-stoichiometric. …

Proteomic Discovery Of Protein Phosphatase 1 Catalytic Subunit Protein Interaction Partners In Human Skeletal Muscle, Zhao Yang

Wayne State University Theses

Protein Phosphatase 1 (PP1), a member of Serine/ Threonine Phosphatase family, targets its dephosphorylation activity on serine and threonine residues. As the catalytic subunit of PP1, PP1c can achieve its substrate specificity only by binding with PP1 regulatory subunits. Previous researches have shown that PP1c can involve in multiple functional regulation by associating with various interaction partners. Since serine/ threonine phosphorylation on the Insulin receptor substrate-1 (IRS1) may direct inactivation and degradation of IRS1, this phosphorylation activity is believed to be a source of Insulin Resistance. PP1 is hypothesized to dephosphorylate serine/ threonine site on IRS1, which may rescue the …

Comparative Study Of The Prevalence Of Psk41 In Heterogenous Vancomycin-Intermediate Staphylococcus Aureus Isolates Against Non- Heterogenous Vancomycin-Intermediate Staphylococcus Aureus Isolates And The Prevalence By Patient Severity, Poorva Mukund Divekar

Wayne State University Theses

COMPARATIVE STUDY OF THE PREVALENCE OF PSK41 IN HETEROGENOUS VANCOMYCIN-INTERMEDIATE STAPHYLOCOCCUS AUREUS ISOLATES AGAINST NON- HETEROGENOUS VANCOMYCIN-INTERMEDIATE STAPHYLOCOCCUS AUREUS ISOLATES AND THE PREVALENCE BY PATIENT SEVERITY

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POORVA DIVEKAR

December 2014

Advisor: Dr. Emily T. Martin

Major: Pharmaceutical Sciences

Degree: Master of Science

Earlier studies have reported that pSK41 plays an important role in the transfer of vancomycin resistance from Vancomycin-resistant Enterococci (VRE) to S. aureus. This transfer leads to the development of Vancomycin-resistant S. aureus (VRSA). Thirteen VRSA cases have been reported in the United States since 2002. To determine and compare the prevalence of pSK41 in hVISA isolates …

Synthesis And Characterization Of Brain Penetrant Prodrug Of Neuroprotective D264: Potential Disease Modifying Treatment Agent For Parkinson's Disease, Fahd Shamoon Dholkawala

Wayne State University Theses

Parkinson's disease (PD) is a complex neurodegenerative disorder with progressive loss of dopamanergic neurons in the substantia nigra region of the brain and accumulation of intracytoplasmic inclusions called `Lewy bodies'. PD is characterized by tremors, rigidity, slowness of movement, bradykinesia and postural imbalances. Although the etiology of PD is not well understood, it is well established that oxidative stress, mitochondrial dysfunction, alpha-synuclein aggregation play a central role in the pathogenesis of PD. Current treatment methods are based on symptomatic relief without addressing the underlying pathophysiological factors responsible for the disease. It is important to develop therapies which can address these …