Pharmacology, Toxicology and Environmental Health Commons^™

Study Of Charge-Dependent Transport And Toxicity Of Peptide-Functionalized Silver Nanoparticles Using Zebrafish Embryos And Single Nanoparticle Plasmonic Spectroscopy, Kerry J. Lee, Lauren M. Browning, Prakash D. Nallathamby, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Nanomaterials possess unusually high surface area-to-volume ratios and surface-determined physicochemical properties. It is essential to understand their surface-dependent toxicity in order to rationally design biocompatible nanomaterials for a wide variety of applications. In this study, we have functionalized the surfaces of silver nanoparticles (Ag NPs, 11.7 ±+2.7 nm in diameter) with three biocompatible peptides (CALNNK, CALNNS, CALNNE) to prepare positively (Ag-CALNNK NPs^+ζ), negatively (Ag-CALNNS NPs^−2ζ), and more negatively charged NPs (Ag-CALNNE NPs^−4ζ), respectively. Each peptide differs in a single amino acid at its C-terminus, which minimizes the effects of peptide sequences and serves as …

Does Nicotine Replacement Therapy Reduce The Withdrawal Symptom Of Craving, Or Urge To Smoke, In Dependent Adult Smokers During Smoking Cessation?, Theresa Dijoseph

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not nicotine replacement therapy reduces the withdrawal symptom of craving, or urge to smoke, in dependent adult smokers during smoking cessation.

STUDY DESIGN: Systematic review of three English language and peer-reviewed randomized-controlled trials published in 2009, 2010, and 2011.

DATA SOURCES: One single-blinded randomized-controlled crossover trial, one double-blinded, placebo controlled, randomized-controlled crossover trial, and one single-blinded, placebo controlled, randomized-controlled crossover trial

OUTCOMES MEASURED: Withdrawal symptoms of craving, irritability, difficulty concentrating, and restlessness were measured on a 100mm visual analog scale (VAS). Adverse effects (AEs) of mouth and …

Acidic Pericellular Ph: Effects On Proteolysis And Gene Expression As Determined In 3d Models Of Breast Carcinoma, Jennifer M. Rothberg

Wayne State University Dissertations

Among the non-cellular microenvironmental factors that contribute to malignancy of solid tumors is an acidic peritumoral pH. The first objective was to determine if an acidic extracellular pH observed in vivo (i.e., pHe 6.8) affects the activity of proteases, such as cathepsin B, that contribute to degradation of collagen IV by tumor cells when grown in biologically relevant three-dimensional cultures. At pHe 6.8 there were increases in pericellular active cysteine cathepsins and in degradation of DQ-collagen IV, which was partially blocked by a cathepsin B inhibitor. Imaging probes for active cysteine cathepsins localized to tumors in vivo. The amount of …

Progress Towards Development Of Multifunctional, Dopamine D2/D3 Receptor Agonists As Symptomatic And Disease-Modifying Therapeutic Agents For Parkinson's Disease, Mark Andrew Johnson

Wayne State University Dissertations

Parkinson¡¯s disease (PD) is a progressive, neurodegenerative disorder that arises primarily through the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), resulting in a diminished level of the neurotransmitter dopamine in the nigrostriatal pathway and ensuing loss of motor function. Common symptoms of PD include resting tremor, muscular rigidity, bradykinesia (slowness and decreased amplitude of movement), along with postural instability and cognitive psychiatric complications. PD affects 1% of the population ¡Ý 65 and is the second most prevalent neurodegenerative disorder next to Alzheimer¡¯s disease (AD). Although the etiology of PD is not yet clear and may be …

Mitochondrial Dna Instability In Cells Lacking Aconitase Correlates With Iron Citrate Toxicity, Muhammad A. Farooq, Tammy M. Pracheil, Zhejun Dong, Fei Xiao, Zhengchang Liu

Biological Sciences Faculty Publications

Aconitase, the second enzyme of the tricarboxylic acid cycle encoded by ACO1 in the budding yeast Saccharomyces cerevisiae, catalyzes the conversion of citrate to isocitrate. aco1 Delta results in mitochondrial DNA (mtDNA) instability. It has been proposed that Aco1 binds to mtDNA and mediates its maintenance. Here we propose an alternative mechanism to account for mtDNA loss in aco1 Delta mutant cells. We found that aco1 Delta activated the RTG pathway, resulting in increased expression of genes encoding citrate synthase. By deleting RTG1, RTG3, or genes encoding citrate synthase, mtDNA instability was prevented in aco1 Delta mutant …

Progress Towards Understanding Of Mechanisms Of Action Of Potent Multifunctional Disease Modifying Therapeutics For Parkinson's Disease & Investigating The Methamphetamine-Induced Striatal Microglia Activation., Mrudang M. Shah

Wayne State University Dissertations

PROGRESS TOWARDS UNDERSTANDING OF MECHANISMS OF ACTION OF POTENT MULTIFUNCTIONAL DISEASE MODIFYING

THERAPEUTICS FOR PARKINSON'S DISEASE.

by

MRUDANG MANOJKUMAR SHAH

December 2013

Advisor: Dr. Aloke Dutta

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Our long term goal is to design and develop potent multifunctional disease modifying therapeutics for Parkinson's disease. The objective of my dissertation was to understand the mechanisms of action of some potent small molecules (synthesized in our lab) as a disease modifying Parkinson's disease therapeutic. The objective was achieved by pursuing the following two specific aims:

1. Investigating anti-oxidant and neuroprotective effects of a lead molecule (D-512) …

Design, Synthesis, Biological Evaluation And Molecular Modeling Studies Of Novel Multifunctional Neuroprotective Drugs For The Treatment Of Parkinson's Disease: An Effort Towards The Improvement Of In Vivo Efficacy And Modulation Of Alpha Synuclein Aggregation Property Of The Neuroprotective Parent, Gyan Prakash Modi

Wayne State University Dissertations

DESIGN, SYNTHESIS, BIOLOGICAL EVALUATION AND MOLECULAR MODELING STUDIES OF NOVEL MULTIFUNCTIONAL NEUROPROTECTIVE DRUGS FOR THE TREATMENT OF PARKINSON'S DISEASE: AN EFFORT TOWARDS THE IMPROVEMENT OF IN VIVO EFFICACY AND MODULATION OF ALPHA SYNUCLEIN AGGREGATION PROPERTY OF THE NEUROPROTECTIVE PARENT MOLECULE (D-264)

by

GYAN PRAKASH MODI

May 2014

Advisor: Dr. Aloke K. Dutta

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Parkinson's disease (PD) is a progressive age-related neurodegenerative disorder of the central nervous system that is characterized by gradual loss of dopaminergic neurons in the substantia nigra region of the brain. The research from the past two decades in PD area …

Insulin Treatment Attenuates Renal Adam17 And Ace2 Shedding In Akita Diabetic Mice, Esam Said Busah Salem

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Diabetic patients have a 40%-50% lifetime chance of developing chronic kidney disease, which remains one of the leading causes of morbidity and mortality. Alterations within renin angiotensin system balance contribute to the pathogenesis of diabetic kidney disease. Angiotensin converting enzyme 2 (ACE2) has an endogenous renoprotective role due to its ability to form angiotensin (1-7) (Ang 1-7) by degrading angiotensin II (Ang II). We have shown previously that hyperglycemia increases urinary ACE2 and albumin excretion in db/db diabetic mice. The protease, disintegrin and metalloprotease (ADAM) 17, is involved in the shedding of several transmembrane proteins, including ACE2 in vitro. Tissue …

Physical Exercise Training But Not Metformin Attenuates Albuminuria And Shedding Of Ace2 In Type 2 Diabetic Db/Db Mice, Hari Krishna Somineni

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Angiotensin II (Ang II), a potent vasoconstrictor cleaved from Ang I, is responsible for renal damage in diabetes. Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and has been shown to be renoprotective by degrading Ang II to Ang-(1-7). A Disintegrin and Metalloproteinases (ADAMs) were recently identified as an ectodomain sheddases of transmembrane proteins. ADAM17 mediated shedding of renal ACE2 could contribute to the pathogenesis of diabetic nephropathy. In our previous study, rosiglitazone treatment normalized hyperglycemia and improved renal injury by preventing ACE2 shedding. The aim of this study is to test the hypothesis that improved glucose …

Bioaccumulation And Neuroinflammation Of Gold Nanoparticles In The Central Nervous System, Fahimeh Fallahi

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Gold nanoparticles (GNPs) possess unique physicochemical properties that may facilitate entry into the central nervous system (CNS) where they may act therapeutically. There is little information on biodistribution or inflammatory effects of GNPs in specific brain regions. Brain Localization and neuroinflammatory response to citrate-capped spherical GNP (10 nm) was determined 24 hours after intravenous (IV) injection in male C57Bl mice. A known inflammogen, lipopolysaccharide (LPS, 2 mg kg-1, SC), was tested as a positive control supplement. Aggregation of GNPs was measured using various Phosphate-Buffered Saline (PBS) concentrations (10, 1, 0.1, 0.01 X) to determine the optimal buffer concentration to maintain …

K-Cl Cotransport: Role Of Kcc3 In Cellular Potassium (K) Homeostasis In Kcc3- Transfected Hek-293 Cells, Nagendra Babu Ravilla

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K-Cl cotransport (KCC) mediated by four protein isoforms, KCC1 to KCC4, plays a significant role in cell volume regulation, and in K and Cl homeostasis. In this study, we demonstrate the importance of KCC3 and its two threonine (T) phosphorylation sites T991 and T1048 in cellular K homeostasis in isogenic human embryonic kidney (HEK-293) cells transfected with KCC3 wild type (WT) or constitutively active double mutant KCC3 (AA) expressed under tetracycline or doxycycline control. In both WT and AA cells, under baseline conditions, the Na-K-2Cl cotransport (NKCC) (55 %- 60 %) was the major contributor of Rb influx followed by …

Chronic Swim Stress Attenuates Endocrine Response And Improves Cardiac Function In Mice Lacking The Angiotensin Ii Type 1a Receptor, Najat Khalifa Almahroug

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Stress is a stimulus that causes an often abrupt but always large change in autonomic activity and hormone secretion. Angiotensin II (AngII) is one of the main neurohormonal mediators that are stimulated by stress. AngII mediates most of its relevant biological effects via AngII type1 receptor (AT1R) activation. Stress increases tissue and circulating levels of Ang II which contributes to stimulation of adrenal AT1R, mediating stressinduced hormone release. Ang II through the activation of AT1R not only elevates blood pressure but also has a patho-physiological relevance in cardiac remodeling. The goal of this study was to assess the influence of …

"Characterization Of Red Diamondback Rattlesnake Venom Proteins On Cell Death And Function", Venus Ebrahimian

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Snake venom is composed of many different toxins and protein components such as metalloproteases and phospholipase A2. Together, these proteins cause an up regulation in cell death pathways and disrupt the overall homeostasis of a living cell. The Red Diamondback Rattlesnake is abundantly available and well-known specie and has been used as a source for development of new drugs. It has been mainly used for the purposes of making anti-venom but it has also been therapeutically used for surgical purposes to act as an anti-aggregate. Integrins derived from RDB venom has been used for cancer cell treatment as well. Specifically …

Locating Chelerythrine, An Alkaloid, Within A Cytosolic Environment By Maldi-Tof Mass Spectrometry, Bradley Allen Williams

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The quaternary benzo-phenanthridine alkaloid (QBA) chelerythrine (CET) is a well-known inhibitor of PKC and cancer growth (Herbert et al., 1990). In human lens epithelial cells (HLECs), CET almost completely inhibits the Na+/K+ pump ATPase (NKA) without changes in phosphorylation (Lauf et al. 2013). Protein alignment studies revealed B-lymphocyte type 2 protein (Bcl-2) BH1- like motifs within the a1 subunit of the NKA to which CET, a drug mimicking Bcl-2 protein BH3-like motifs, might bind thus disrupting NKA function (Lauf et al, 2013). It is unknown by which mechanism CET crosses the plasma membrane to reach its intracellular targets, especially the …

Effects Of Red Diamondback Rattlesnake Venom On Keloid Dermal Fibroblasts In Vitro, Mackenzie Shelby Newman

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Keloid scarring is an inflammatory healing response to physical injury such as incision or piercing in the dermis. It is characterized by aberrant extracellular matrix production, the overaccumulation of mature collagen, and excessive fibroblast proliferation and migration beyond the borders of the original wound site. This results in swelling, depigmentation, itchiness, and pain akin to a benign tumor. Although there are myriad treatments for the condition, most are invasive and exhibit a high recurrence rate. Previous studies have shown that rattlesnake venom stimulates apoptosis in the skin via multiple specific mechanisms, largely composed of extracellular matrix and its receptors' interactions. …

Effects Of Ang 1-7 And Endothelial Microvesicles On Ang Ii-Induced Dysfunction And Apoptosis In Cerebral Endothelial Cells, Xiang Xiao

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Angiotensin II (Ang II) induces endothelial dysfunction and is implicated in the pathogenesis of vascular diseases. Angiotensin 1-7 (Ang 1-7) has been reported to counteract many deleterious effects of Ang II. Endothelial microvesicles (EMVs) are small membrane vesicles released from endothelial cells (ECs) undergoing stress and apoptosis. But their functions are largely unknown. In this study, we investigated the effects of Ang 1-7 and EMVs on apoptosis and dysfunction of human brain microvascular endothelial cells (HbmECs). Reactive oxygen species (ROS) and nitric oxide (NO) production, and Nox2, p-Akt/Akt, p-eNOS/eNOS expression were analyzed. We found that Ang II dose-dependently induced HbmEC …

Role Of Bax, Ibpa, Ibpb And Csph Genes In Protecting Cft073 (Uropathogenic Escherichia Coli) Against Salt And Urea Stress, Pavani Beesetty

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Uropathogenic Escherichia coli (UPEC) are the primary cause of 80 to 90% of uncomplicated urinary tract infections. After entering the urinary tract, uropathogenic E.coli has to tolerate high levels of salt and urea in urine to cause a successful infection. The osmotic stress imposed by urea is different from that by NaCl, as urea can freely move across the cell membrane and is a protein denaturant. Hence, microarray experiments were performed to observe the differential expression of genes in CFT073 (UPEC) due to the presence of 0.3 M NaCl and 0.6 M urea in K medium individually. Based on the …

Tolfenamic Acid Induces Cell Apoptosis And Inhibits Collagen Accumulation In Keloid Fibroblasts, Dan Yi

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Keloid scar is a fibroproliferative disorder which results from the accumulation of collagen through the activation of TGF-B/Smad signaling. Tolfenamic acid (TA) has been found to inhibit collagen synthesis in animal and induce cancer cell apoptosis. In this study, we investigated the effect of DMSO on cell apoptosis, TA on collagen deposition, and TA on collagen type I and smad2 protein expression in human normal fibroblasts (NFs) and human keloid fibroblasts (KFs). In the dose- and exposure time- response assays, we found that 1% DMSO for 48h treatment did not obviously induce NF and KF apoptosis and that 0.55x10-3 M …

The Aryl Hydrocarbon Receptor Regulates An Essential Transcriptional Element In The Immunoglobulin Heavy Chain Gene, Michael J. Wourms

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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that inhibits immunoglobulin (Ig) expression and Ig heavy (IgH) chain gene transcription. Transcription of the IgH gene involves several regulatory elements including the 3'lgh regulatory region (3'lghRR) which is composed of four enhancers (hs3A, hs1,2, hs4, and hs3B). Dioxin responsive elements (DRE) in the hs4 and hs1,2 enhancers of the 3lghRR that bind the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that regulates dioxin sensitive genes suggest that the 3'lghRR may be a transcriptional target of TCDD. The current study utilized an IgA secreting mouse …

Evaluation Of A Novel Rapid Diagnostic Test For Schistosoma Haematobium Based On The Detection Of Human Immunoglobulins Bound To Filtered Schistosoma Haematobium Eggs, Johnathan M. Sheele, Jimmy H. Kihara, Sarah Baddorf, Jonathan Byrne, Bhaskara Ravi

Mathematics & Statistics Faculty Publications

Objectives To determine whether the detection of human IgG bound to Schistosoma haematobium eggs from filtered urine could be used as a rapid diagnostic test (RDT-Sh).

Methods We filtered 160 urine samples from children in the Kwale District of Kenya to isolate S.haematobium eggs and used anti-human IgG antibody conjugated to horseradish peroxidase to bind to the human IgG attached to the eggs. We then added 3,35,5-tetramethylbenzidine base (TMB), which turns blue in the presence of horseradish peroxidase to detect the S.haematobium eggs. The RDT-Sh was compared in a blinded manner to urine microscopy.

Results The RDT-Sh was positive in …

Non-Cytotoxic Antibacterial Silver–Coumarin Complex Doped Sol–Gel Coatings, Swarna Jaiswal, Kunal Bhattacharya, Maeve Sullivan, Maureen Walsh, Bernadette Creaven, Fathima Laffir, Brendan Duffy, Patrick Mchale

Articles

Microbial colonisation on clinical and industrial surfaces is currently of global concern and silane based sol–gel coatings are being proposed as potential solutions. Sol–gels are chemically inert, stable and homogeneous and can be designed to act as a reservoir for releasing antimicrobial agents over extended time periods. In the present study, silver nitrate (AgN) and a series of silver coumarin complexes based on coumarin-3-carboxylatosilver (AgC) and it is 6,7 and 8 hydroxylated analogues (Ag6, Ag7, Ag8) were incorporated into sol–gel coatings. The comparative antibacterial activity of the coatings was determined against meticillin resistant Staphylococcus aureus (MRSA) and multidrug resistance Enterobacter …

Influence Of Surface Modification On Properties And Applications Of Complex Engineered Nanoparticles, Binghui Wang

Theses and Dissertations--Chemical and Materials Engineering

Complex engineered nanoparticles (CENPs) are being used on various applications. Their properties are different from those of neat nanoparticles. The dissertation explores these differences from four aspects: 1) Modify carbon nanomaterials’ inert surfaces and investigate the effect on thermal and rheological behavior of their dispersions; 2) Generate self-assembly bi-layer structure of oxide nanoparticles via surface modification; 3) Study interaction between lysozyme and different surface-charged ceria nanoparticles; 4) Investigate the biodistribution and transformations of CENPs in biological media.

An environment-friendly surface modification was developed to modify surfaces of carbon nanomaterials for increasing their affinity to non-polar fluid. It can offset formation …

Formulation And Evaluation Of Verapamil Hydrochloride Transmucosal Drug Delivery System, Subhash Chandra Bose Penjuri, Saritha Damineni, Nagaraju Ravouru

The Thai Journal of Pharmaceutical Sciences

Verapamil hydrochloride is an antihypertensive agent which undergoes extensive first pass metabolism making it a possible candidate for buccal delivery. Verapamil mucoadhesive buccal patches were prepared using hydroxypropyl methylcellulose, Eudragit RL ...

Development And Validation Of A Simple Stability Indicating Uplc Method For The Determination Of Repaglinide In Pharmaceuticals, Cjjo M. Xavier, Kanakapura Basavaiah

The Thai Journal of Pharmaceutical Sciences

A simple, precise and accurate stability-indicating isocratic reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for the determination of repaglinide (RPG) in bulk drug and in its tablets. The method was developed using Waters Aquity BEH C18 (100 Ó 2.1) mm, 1.7 μm column with mobile phase consisting of a mixture of potassium dihydrogen phosphate buffer of pH 3.2 and acetonitrile (40:60 v/v). The total run time for the assay was only 4 min. The eluted compound was detected at 245 nm with an UV detector. The standard curve of mean peak area versus concentration showed an excellent linearity …

Selective And Sensitive Assay Of Mebendazole In Pharmaceuticals Using Bromocresol Green By Spectrophotometry, N. Swamy, K. Basavaiah

The Thai Journal of Pharmaceutical Sciences

Three new, simple, rapid and sensitive spectrophotometric methods have been developed for the assay of mebendazole (MBD) in bulk drug, tablets and suspension. First method (method A) is based on the formation of a colored ion-pair complex (1:1 drug/dye) ...

Effect Of Ethanol Concentration On Cyanidin-3-Glucoside, Total Monomeric Anthocyanins, Total Phenolic Content And Radical Scavenging Properties In Purple Corn (Zea Mays L.) Seed And Cob., Penpan Srithong, Tanwarat Kajsongkram, Chuleratana Bangchonglikitkul, Waraporn Boonsupthip

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Comparison Of Hplc And Tlc Densitometric Methods For The Quantification Of Rhein In Cassia Fistula Pod Pulp Extract, Savita Chewchinda, Pongtip Sithisam, Wandee Gritsanapan

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Nutritional Values And Tlc Fingerprint Of Scaphium Scaphigerum Fruit Gel, Wichittra Phlicharoenphon., Wandee Gritsanapan, Pongtip Sithisarn

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Application Of Titrimetric Indicator To The Estimation Of Polyplex Formation Ratio Between Chitosan Polymer And Plasmid Dna Used For Gene Delivery Formulation, Samarwadee Plianwong., Praneet Opanasopit, Tanasait Ngawhirunpat, Theerasak Rojanarata

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Preparation Of Doubly Crosslinked Chitosan By The Use Of Environmentally Friendly Crosslinkers For Enzyme Immobilization, Siripran Tidiarat, Tanasait Ngawhirunpat, Praneet Opanasopit, Theerasak Rojanarata

The Thai Journal of Pharmaceutical Sciences

No abstract provided.