Pharmacology Commons^™

Heavy Metal Content In Some Commonly Consumed Vegetables From Kariakoo Market, Dar Es Salaam, Tanzania, Eb Mubofu

Tanzania Journal of Science

This work reports on the levels of cadmium, lead, copper, manganese and zinc in 174 samples from eight varieties of green vegetables (amaranth, Chinese cabbage, cowpea leaves, green pepper, leafy cabbage, lettuce, okra and pumpkin leaf) commonly grown in Dar es Salaam and marketed at Kariakoo, Tanzania. The amount of cadmium and lead ranged between 3-42 and 11-60 μg/kg respectively. The amount of copper, manganese and zinc ranged between 0.35 - 2.12, 1.01 - 7.57, and 1.19 - 6.33 μg/kg respectively. On average consumption pattern, the contribution of these vegetables to the recommended daily intakes (RDI) for cadmium and lead …

Tremulous Jaw Movements Induced By The Vmat2 Inhibitor Tetrabenazine, Samantha J. Podurgiel

Master's Theses

Parkinsonism is a movement disorder characterized by several cardinal motor symptoms: resting tremor, akinesia, bradykinesia, rigidity, and postural instability. Parkinsonian resting tremor can be modeled in rodents using the tremulous jaw movement model. Tremulous jaw movements (TJMs) are defined as “rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus.” TJMs occur in a frequency range of 3-7 Hz and are induced by a number of pharmacological manipulations that parallel those seen in human Parkinsonism including dopamine (DA) depleting agents, DA antagonists, and cholinomimetic administration. Additionally, TJMs can be attenuated using antiparkinsonian …

Characterisation Of Pharmaceutical Grade Horse Chestnut Waste, Joanna Przyborska

Theses

Horse chestnut residue was made available by a local pharmaceutical company. The residue was subjected to compositional analysis and studied to determine potential for residual biological activity, including prebiotic, antimicrobial, anti-hyaluronidase and anti-elastase effects.

The residue had 52 % total solids, including 2.97% ash, 6.93% protein, 1.89% crude fat. Oleic acid (74.7%) was the main fatty acid components in the crude lipid component. The major ash components were potassium, phosphorus, calcium and magnesium.

Prebiotic potential of aqueous extract (HCE) from horse chestnut residue was confirmed. A new formula for calculation of prebiotic index (PI) was developed. PI for probiotics (Lactobacillus …

Cocaine-Induced Reinstatement Of A Conditioned Place Preference In Developing Rats: Involvement Of The D2 Receptor, Kimberly A. Badanich, Cheryl L. Kirstein

Psychology Faculty Publications

Reinstatement of conditioned place preferences have been used to investigate physiological mechanisms mediating drug-seeking behavior in adolescent and adult rodents; however, it is still unclear how psychostimulant exposure during adolescence affects neuron communication and whether these changes would elicit enhanced drug-seeking behavior later in adulthood. The present study determined whether the effects of intra-ventral tegmental area (VTA) or intra-nucleus accumbens septi (NAcc) dopamine (DA) D2 receptor antagonist infusions would block (or potentiate) cocaine-induced reinstatement of conditioned place preferences. Adolescent rats (postnatal day (PND 28–39)) were trained to express a cocaine place preference. The involvement of D2 receptors on cocaine-induced reinstatement …

Anti-Cancer Activity And Mutagenic Potential Of Novel Copper (Ii) Quinolinone Schiff Base Complexes In Hepatocarinoma Cells, Brian Duff, Venkat Reddy Thangella, Bernadette Creaven, Maureen Walsh, Denise Egan

Articles

This study determined the cytotoxic, cyto-selective and mutagenic potential of novel quinolinone Schiff base ligands and their corresponding copper(II) complexes in human-derived hepatic carcinoma cells (Hep-G2) and non-malignant human-derived hepatic cells (Chang). Results indicated that complexation of quinolinone Schiff bases with copper served to significantly enhance cytotoxicity. Here, the complex of (7E)-7-(3-ethoxy-2-hydroxybenzylideamino)-4-methylquinolin-2(1H)-one (TV117-FM) exhibited the lowest IC₅₀ value (17.9 μM) following 96 h continuous exposure, which was comparable to cisplatin (15.0 μM). However, results revealed that TV117-FM lacked cytoselectivity over non-malignant cells. Additionally, the complex was minimally effluxed from cells via Pglycoprotein (P-gp) and was shown to be non-mutagenic …

Physiologically-Based Pharmacokinetic Modeling Of Acetaminophen Metabolism And Toxicity, David M. Ng, Ali Navid

STAR Program Research Presentations

Acetaminophen is a common analgesic and antipyretic. Metabolism of acetaminophen and acetaminophen-induced liver necrosis are predicted using physiologically-based pharmacokinetic (PBPK) modeling. Pharmacokinetic means the model determines where the drug is distributed in the body over time. Physiologically-based means the anatomy and physiology of the human body is reflected in the structure and functioning of the model. Acetaminophen is usually safe and effective when taken as recommended, but consumption at higher levels may lead to liver damage. Additionally, other factors such as alcoholic liver disease, smoking, and malnutrition affect the maximum safe dose of acetaminophen.

Correlation Of In-Vitro Drug Dissolution And In-Vivo Drug Absorption Of Various Therapeutically Equivalent Pharmaceutical Solid Dosage Forms Of Simvastatin, Aphrodite Kotrotsios

PCOM Biomedical Studies Student Scholarship

Simvastatin is a well known anti-cholesterol drug that is commercially available in the United States in various strengths including Simvastatin Tablets, USP 80 mg, that are under the brand name Zocor (manufactured by Merck Pharmaceutical Co.) and various generic equivalent products for example those manufactured by Teva Pharmaceuticals, Inc. and Dr. Reddy’s Laboratories, Ltd. When generic products are tested in the United States, they must be found to be equivalent with their branded products by the FDA. Therefore, generic Simvastatin Tablets, USP 80 mg, have been tested and approved by the FDA as equivalents to, and substitutable with, the branded …

Localization And Expression Of Gfrα2 Receptors In Neonatal And Adolescent Mouse Heart., Bryan Gunter

Undergraduate Honors Theses

Neurturin (NRTN), a member of the glial cell-line derived neurotrophic factor(GDNF) family, is required in the development of parasympathetic cholinergic neurons. It signals through binding to a glycosyl-phophatidyl inositol (GPI)-linked receptor, GDNF family receptor α2 (GFRα2), which couples to Ret tyrosine kinase. Studies of NRTN knockout mice have shown that NRTN is essential for normal cholinergic innervation of the heart, but the precise role of NRTN remains unknown. For NRTN to evoke a biological response, GFRα2 must be localized to the surface of target neurons. The aim of this study was to determine the expression and localization of GFRα2 at …

Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof

Dissertations and Theses (Open Access)

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …

A Pre-Clinical Assessment Of Minocycline For Treatment Of Chronic Neuropathic Pain After Spinal Cord Injury, Alissa R. Poteete

Dissertations and Theses (Open Access)

Patients living with a spinal cord injury (SCI) often develop chronic neuropathic pain (CNP). Unfortunately, the clinically approved, current standard of treatment, gabapentin, only provides temporary pain relief. This treatment can cause numerous adverse side effects that negatively affect the daily lives of SCI patients. There is a great need for alternative, effective treatments for SCI-dependent CNP.

Minocycline, an FDA-approved antibiotic, has been widely prescribed for the treatment of acne for several decades. However, recent studies demonstrate that minocycline has neuroprotective properties in several pre-clinical rodent models of CNS trauma and disease. Pre-clinical studies also show that short-term minocycline treatment …

Cosmetic Neurology: Enhancement Of The Mind And Attention Deficit Hyperactive Disorder Medication Abuse Among College Students, Mary M. Huff

Senior Honors Theses

Cosmetic neurology is becoming increasingly popular, and it is not just sleep deprived, over worked college students who are interested. People are beginning to seek off-label prescriptions for medications that are typically used to treat disorders such as attention deficit hyperactive disorder (ADHD) or narcolepsy, while researchers are trying to create drugs used solely for mind enhancement purposes. Along with these drugs come many legal and ethical quandaries relating to the regulation of current use as well as the what ifs of future possibilities. A survey was conducted among college students regarding the diagnosis of ADHD, the abuse of ADHD …

Planarians In Pharmacology: Parthenolide Is A Specific Behavioral Antagonist Of Cocaine In The Planarian Girardia Tigrina, Oné R. Pagán, Debra Baker, Sean Deats, Erica Montgomery, Matthew Tenaglia, Clinita Randolph, Dharini Kotturu, Christopher Tallarida, Daniel Bach, Galia Wilk, Scott Rawls, Robert B. Raffa

Biology Faculty Publications

Planarians are traditional animal models in developmental and regeneration biology. Recently, these organisms are arising as vertebrate-relevant animal models in neuropharmacology. Using an adaptation of published behavioral protocols, we have described the alleviation of cocaine-induced planarian seizure-like movements (pSLM) by a naturally-occurring sesquiterpene lactone, parthenolide. Interestingly, parthenolide does not prevent the expression of pSLM induced by amphetamines; in vertebrates, amphetamines interact with the same protein target as cocaine. Parthenolide is also unable to prevent pSLM elicited by the cholinergic compounds nicotine and cytisine or by the glutamatergic agents L- or D- glutamic acid or NMDA. Thus, we conclude that parthenolide …

The Cyclin-Like Protein Spy1/Ringo Promotes Mammary Transformation And Is Elevated In Human Breast Cancer, Mohammad Al Sorkhy, Rosa-Maria Ferraiuolo, Espanta Jalili, Agnes Malysa, Andreea R. Fratiloiu, Bonnie F. Sloane, Lisa A. Porter

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Spy1 is a novel 'cyclin-like' activator of the G1/S transition capable of enhancing cell proliferation as well as inhibiting apoptosis. Spy1 protein levels are tightly regulated during normal mammary development and forced overexpression in mammary mouse models accelerates mammary tumorigenesis.

Methods

Using human tissue samples, cell culture models and in vivo analysis we study the implications of Spy1 as a mediator of mammary transformation and breast cancer proliferation.

Results

We demonstrate that this protein can facilitate transformation in a manner dependent upon the activation of the G2/M Cdk, Cdk1, and the subsequent inhibition of the anti-apoptotic regulator FOXO1. …

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 …

Analysis Of Gene Expression Alterations In Premalignant Progression From Normal Mammary Epithelium To Ductal Carcinoma In Situ By Multiple Orthogonal Tools, Hitchintan Kaur

Wayne State University Dissertations

Mammary ductal carcinoma in situ (DCIS) is being found in great numbers of women due to the widespread use of mammography. The molecular and genetic changes underlying the progression from normal breast tissue to DCIS are not clearly understood. The goal of the present study was to determine gene expression changes in different DCIS models (MCF10.DCIS, SUM102 and SUM225) in comparison to normal breast epithelial cells (MCF10A) that may enable us to identify novel markers of disease progression and potential therapeutic targets. We cultured the cells in three dimensional reconstituted basement membrane (3D rBM) for RNA extraction and used the …

Compositional Determinants Of The Pharmacological Actions Of Heparins, Angel Lee Gray-Shah

Dissertations

This dissertation primarily focuses on how differences in molecular weight (MW) and structural composition affect the pharmacological activity of heparin and its derivatives. Heparins are a mixture of glycosaminoglycans chains which are used to prevent thrombosis in a number of clinical indications. Heparins promote the inhibition of blood coagulation via their plasmatic cofactors antithrombin (AT) and heparin cofactor II (HCII).

In these studies, various heparins with molecular weights ranging from 2.6 to 16.5 kDa were investigated. Not only the molecular weight but also the oligosaccharide composition greatly varied in these agents. One of the major objectives of this research was …

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 …

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 …

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.

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 …

Mutation In The Plasmodium Falciparum Crt Protein Determines The Stereospecific Activity Of Antimalarial Cinchona Alkaloids, Carol E. Griffin, Jonathan M. Hoke, Upeka Samarakoon, Junhui Duan, Jianbing Mu, Michael T. Ferdig, David C. Warhurst, Roland A. Cooper

Biological Sciences Faculty Publications

The Cinchona alkaloids are quinoline aminoalcohols that occur as diastereomer pairs, typified by (-)-quinine and (+)-quinidine. The potency of (+)-isomers is greater than the (-)-isomers in vitro and in vivo against Plasmodium falciparum malaria parasites. They may act by the inhibition of heme crystallization within the parasite digestive vacuole in a manner similar to chloroquine. Earlier studies showed that a K76I mutation in the digestive vacuole-associated protein, PfCRT (P. falciparum chloroquine resistance transporter), reversed the normal potency order of quinine and quinidine toward P. falciparum. To further explore PfCRT-alkaloid interactions in the malaria parasite, we measured the in …

Quercetin And Derivatives As Butyrylcholinesterase Inhibitors, Siriluk Sontadsakul, Anchisa Prakongsantikul, Worawan Kitphati, Jaturong Pratuangdejkul, Veena Nukoolkam

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Biological Activities Of A Patented Mix Extract From Fruits Of Phyllanthus Emblica And Zanthoxylumlimonella, Buppachart Potduang, Bundit Fungsin, Isara Keeta, Natthachest Ketmanee, Anintitha Intharungsri, Sitthiphong Soradech, Cholticha Niwaspragrit, Sayan Tanpanich

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Anti-Periodontal Bacterial Activity Of Oxyresveratrol, Waranvoo Phoolcharoen, Sireerat Sooampon, Boonchoo Sritularak, Kittisak Likhitvitayawuid, Jintakom Kuvatanasuchati, Prasit Pavasant

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Microemulsion Formulation Of Angelica Sinensis Root Extract On Clove Oil /Nonionic Surfactant/ Water Mixture, Pichaya Ukosaramik, Prasan Tangyuenyongwatana, Rathapon Asasutjarit

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Xanthones And Biphenyls From Garcinia Schomburgkiana Wood And Their Cytotoxicity, Chutichot Mungmee, Supotchana Sitthigool, Rutt Suttisri, Anumart Buakeaw

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Purification And Characterization Of Chemical Marker Compound From Azadirachta Indica Var. Siamensis Flowers, Noppunt Prakitboonyarit, Thitima Lhinhatrakool, Prasan Tanguenyongwatana

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Determination Of Some Phenolic Compounds In Ethanolic Extract Of Elephantopus Scaber Linn. Leaves, Ubon Rerk-Am, Bantika Kongsombat, Sinn Tangsatirapakdee, Chuleratana Banchonglikitkul

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Free Radical Scavenging Activity, Total Phenolic And Total Anthocyanin Contents Of Extracts From Mamao (Antidesma Ghaesembilla) Fruits, Paponpat Worasakungiat, Apirat Jamnonkoon, Wandee Gritsanapan, Pongtio Sithisam

The Thai Journal of Pharmaceutical Sciences

No abstract provided.