Chemicals and Drugs Commons^™

The Biologics Price Competition And Innovation Act: Is A Generic Market For Biologics Attainable?, Kasey E. Koballa

William & Mary Business Law Review

The Biologics Price Competition and Innovation Act of 2009 (BPCIA) provides an abbreviated approval pathway for biological therapeutic products shown to be biosimilar to an FDA-approved biological reference product. The BPCIA purported to reduce the price of biologics while promoting innovation. In two recent cases, the Federal Circuit interpreted a key provision of the BPCIA requiring an applicant to provide the reference product sponsor with notice 180 days before marketing the product. The Federal Circuit’s interpretation extends the exclusivity period already provided for the reference product sponsor, deterring innovation and price reduction. Thus, the Supreme Court granted certiorari in one …

February 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Relationship Between The Dimerization Of Thyroglobulin And Its Ability To Form Triiodothyronine, Cintia E. Citterio, Yoshiaki Morishita, Nada Dakka, Balaji Veluswamy, Peter Arvan

Pharmacy Faculty Articles and Research

Thyroglobulin (TG) is the most abundant thyroid gland protein, a dimeric iodoglycoprotein (660 kDa). TG serves as the protein precursor in the synthesis of thyroid hormones tetraiodothyronine (T₄) and triiodothyronine (T₃). The primary site for T₃ synthesis in TG involves an iodotyrosine acceptor at the antepenultimate Tyr residue (at the extreme carboxyl terminus of the protein). The carboxyl-terminal region of TG comprises a cholinesterase-like (ChEL) domain followed by a short unique tail sequence. Despite many studies, the monoiodotyrosine donor residue needed for the coupling reaction to create T₃ at this evolutionarily conserved …

The Winding Road To Relapse: Forging A New Understanding Of Cue-Induced Reinstatement Models And Their Associated Neural Mechanisms, Mark D. Namba, Seven E. Tomek, M. Foster Olive, Joshua S. Beckmann, Cassandra D. Gipson

Psychology Faculty Publications

In drug addiction, cues previously associated with drug use can produce craving and frequently trigger the resumption of drug taking in individuals vulnerable to relapse. Environmental stimuli associated with drugs or natural reinforcers can become reliably conditioned to increase behavior that was previously reinforced. In preclinical models of addiction, these cues enhance both drug self-administration and reinstatement of drug seeking. In this review, we will dissociate the roles of conditioned stimuli as reinforcers from their modulatory or discriminative functions in producing drug-seeking behavior. As well, we will examine possible differences in neurobiological encoding underlying these functional differences. Specifically, we will …

Insulin-Degrading Enzyme Is Not Secreted From Cultured Cells, Eun Suk Song, David W. Rodgers, Louis Hersh

Molecular and Cellular Biochemistry Faculty Publications

Insulin-degrading enzyme (IDE) functions in the catabolism of bioactive peptides. Established roles include degrading insulin and the amyloid beta peptide (Aβ), linking it to diabetes and Alzheimer’s disease. IDE is primarily located in the cytosol, and a longstanding question is how it gains access to its peptide substrates. Reports suggest that IDE secreted by an unconventional pathway participates in extracellular hydrolysis of insulin and Aβ. We find that IDE release from cultured HEK-293 or BV-2 cells represents only ~1% of total cellular IDE, far less than has been reported previously. Importantly, lactate dehydrogenase (LDH) and other cytosolic enzymes are released …

Synthesis, Characterization, And In Vitro Cytotoxicity Of Fatty Acyl-Cgkrk-Chitosan Oligosaccharides Conjugates For Sirna Delivery, Naglaa Salem El-Sayed, Meenakshi Sharma, Hamidreza Montazeri Aliabadi, Magda Goda El-Meligy, Ahmed Kamed El-Zaity, Zenat Adeeb Nageib, Rakesh Tiwari

Pharmacy Faculty Articles and Research

In this studies, three fatty acyl derivatives of CGKRK homing peptides were coupled successfully to chitosan oligosaccharides (COS) using sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate sodium salt (sulfo-SMCC). The COS-SMCC was prepared by direct coupling between COS and sulfo-SMCC in PBS (pH 7.5) at RT for 48 h. The structure of COS-SMCC and the three fatty acyl-CGKRK-SMCC-COS conjugates were characterized by FT-IR, ¹³C NMR, and SEM. The ability of three conjugates to condense siRNA into nanosized polyplexes and their efficacy in protecting siRNA from serum nucleases degradation were investigated. Among the investigated derivatives, S-CGKRK-COS showed higher siRNA binding affinity as compared to …

The Effect Of Grapefruit Intake On Endogenous Serum Estrogen Levels In Postmenopausal Women, Kristine R. Monroe, Frank Z. Stanczyk, Kathleen Hill-Besinque, Malcolm C. Pike

Pharmacy Faculty Articles and Research

Although grapefruit intake leads to elevated serum estrogen levels when hormones are taken orally, there are no published data on the effect on endogenous levels. We conducted a pilot dietary intervention study among healthy postmenopausal volunteers to test whole grapefruit, 2 juices, and 1 grapefruit soda. Fifty-nine participants were recruited through the Love/Avon Army of Women. The study consisted of a 3-wk run-in, 2 wk of grapefruit intake, and a 1-wk wash-out. Eight fasting blood samples were collected. An additional 5 samples drawn at 1, 2, 4, 8, and 10 hr after grapefruit intake were collected during an acute-phase study …

Simian Virus 40 Large T Antigen As A Model To Test The Efficacy Of Flouroquinolones Against Viral Helicases, Sammer Siddiqui, Muhammad F. Anwar, Sadaf Naeem, Syed Hani Abidi, Shamshad Zarina, Syed Ali

Department of Biological & Biomedical Sciences

Simian virus 40 large T-antigen (SV40 LT-Ag) is a 708 amino acid nuclear phosphoprotein. Among many functions of LT-Ag is its ability to perform as an ATPase-helicase, catalyzing the unwinding of viral genome during replication. The LT-Ag has been employed in the studies of helicase structure and function, and has served as a model helicase for the screening of antiviral drugs that target viral helicase. In this study, using in vitro enzyme assays and in silico computer modeling, we screened a batch of 18 fluoroquinolones to assess their potential as antivirals by virtue of their inhibition of the LT-Ag helicase. …

Novel Combination Bmp7 And Hgf Gene Therapy Instigates Selective Myofibroblast Apoptosis And Reduces Corneal Haze In Vivo, Suneel Gupta, Michael K. Fink, Arkasubhra Ghosh, Ratnakar Tripathi, Prashant R. Sinha, Ajay Sharma, Nathan P. Hesemann, Shyam S. Chaurasia, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. We tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models.

METHODS. Eighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n ¼ 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n ¼ 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n ¼ 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic studies. …

Inactivation Of Myeloma Cancer Cells By Helium And Argon Plasma Jets: The Effect Comparison And The Key Reactive Species, Zeyu Chen, Qingjie Cui, Chen Chen, Dehui Xu, Dingxin Liu, H. L. Chen, Michael G. Kong

Bioelectrics Publications

In plasma cancer therapy, the inactivation of cancer cells under plasma treatment is closely related to the reactive oxygen and nitrogen species (RONS) induced by plasmas. Quantitative study on the plasma-induced RONS that related to cancer cells apoptosis is critical for advancing the research of plasma cancer therapy. In this paper, the effects of several reactive species on the inactivation of LP-1 myeloma cancer cells are comparatively studied with variable working gas composition, surrounding gas composition, and discharge power. The results show that helium plasma jet has a higher cell inactivation efficiency than argon plasma jet under the same discharge …

Reproductive Steroids And Adhd Symptoms Across The Menstrual Cycle, Bethan A. Roberts, Tory Eisenlohr-Moul, Michelle M. Martel

Psychology Faculty Publications

Although Attention-Deficit/Hyperactivity Disorder shows (ADHD) male predominance, females are significantly impaired and exhibit additional comorbid disorders during adolescence. However, no empirical work has examined the influence of cyclical fluctuating steroids on ADHD symptoms in women. The present study examined estradiol (E2), progesterone (P4), and testosterone (T) associations with ADHD symptoms across the menstrual cycle in regularly-cycling young women (N=32), examining trait impulsivity as a moderator. Women completed a baseline measure of trait impulsivity, provided saliva samples each morning, and completed an ADHD symptom checklist every evening for 35 days. Results indicated decreased levels of E2 in the context of increased …

Neurotensin Receptor 3/Sortilin Contributes To Tumorigenesis Of Neuroendocrine Tumors Through Augmentation Of Cell Adhesion And Migration, Ji Tae Kim, Dana L. Napier, Heidi L. Weiss, Eun Y. Lee, Courtney M. Townsend, B. Mark Evers

Markey Cancer Center Faculty Publications

Neurotensin (NTS), a 13–amino acid peptide which is distributed predominantly along gastrointestinal tract, has multiple physiologic and pathologic functions, and its effects are mediated by three distinct NTS receptors (NTSRs). Overexpression and activation of NTS signaling components, especially NTS and/or NTSR1, are closely linked with cancer progression and metastasis in various types of cancers including neuroendocrine tumors (NETs). Although deregulation of NTSR3/sortilin has been implicated in a variety of human diseases, the expression and role of NTSR3/sortilin in NETs have not been elucidated. In this study, we investigated the expression and oncogenic effect of NTSR3/sortilin in NETs. Increased protein levels …

Microrna 1207-3p In Prostate Cancer, Dibash Das

Dissertations, Theses, and Capstone Projects

Prostate cancer (PCa) is the most commonly diagnosed male cancer and the second leading cause of cancer-related death for men in the United States. Understanding the molecular mechanisms involved in progression from the asymptomatic androgen-dependent PCa to the lethal castration resistant prostate cancer (CRPC) is a major challenge. MicroRNAs (miRNAs), are known to be dysregulated in PCa. MicroRNA-1207-3p (miR-1207-3p) is encoded by the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of miR-1207-3p in PCa is unclear. We have discovered that miR-1207-3p is significantly underexpressed in PCa cell lines …

New Dyes For Cancer Theranostics, Waqar Rizvi

Dissertations, Theses, and Capstone Projects

Porphyrinoids are robust heterocyclic dyes studied extensively for applications in medicine and as photonic materials because of their tunable photophysical properties, diverse means of modifying the periphery, and the ability to chelate most transition metals. Commercial applications include phthalocyanine dyes in optical discs, porphyrins in photodynamic therapy, and as oxygen sensors. Most applications of these dyes require exocyclic moieties to improve solubility, target disease, modulate photophysical properties, or direct self-organization into architectures with desired photonic properties. The synthesis of the porphyrinoid depends on the desired application, but the de novo synthesis often involves several steps, is time consuming, and results …

Bacterial Lps At The Immune Modulating Component In Juzen-Taiho-To, Diego Montenegro

Dissertations, Theses, and Capstone Projects

Juzen-taiho-to (JTT) is an immune-boosting herbal formulation with an ideal balance of safety and efficacy. For example, JTT is clinically used in Japan to stimulate the immunological functions of cancer patients undergoing chemotherapy and radiation. Although the clinical effects of JTT are recognized, the active compounds and mechanism of action are unknown. The studies conducted previously in our laboratory associated several phytosterols and plant glycolipids with the potent immunostimulatory activity of JTT: namely, β-sitosteryl β-D-glucoside (BSSG), glucocerebroside (GluCer), digalactosyldiacylglycerol (DGDG) and monogalactosyldiacylglycerol (MGDG). However, these compounds, when further purified, exhibited little or no immunostimulatory activity. This suggested that the immunostimulatory …

Human Factors Contributing To Preventable Adverse Drug Events In Healthcare: A Grounded Theory Approach Pilot Study, Thomas Ryan Hilgers

Doctoral Dissertations and Master's Theses

The following thesis details a grounded theory methodology (GT) pilot study of preventable adverse drug events (pADEs) in healthcare. This research used the methodological approach to develop a categorical theory for the chief workplace contributors to intra-hospital intensive care unit (ICU) preventable adverse drug events. While this study represents only a foray into the use of GT to explain pADEs, the results implicate specific areas of concern that may be followed up on in future qualitative or quantitative research. Pursuant of a Straussian grounded theory methodology, this study leaned fundamentally on the interview of individuals with first-hand experience with the …

Amine Containing Analogs Of Sulindac For Cancer Prevention, Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds

Pharmaceutical Sciences Faculty Publications

Background:

Sulindac belongs to the chemically diverse family of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) that effectively prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindac sulfide amide (SSA), an amide analog of sulindac sulfide, shows insignificant COX-related activity and toxicity while enhancing anticancer activity in vitro and demonstrating in vivo xenograft activity.

Objective:

Develop structure-activity relationships in the sulindac amine series and identify analogs with promising anticancer activities.

Method:

A series of sulindac amine analogs were designed and synthesized and then further modified in a “libraries from libraries” approach to produce amide, sulfonamide and N,N-disubstituted …

Regulation Of Kv2.1 Channel Inactivation By Phosphatidylinositol 4,5-Bisphosphate., Mayra Delgado-Ramírez, José J De Jesús-Pérez, Iván A Aréchiga-Figueroa, Jorge Arreola, Scott K Adney, Carlos A. Villalba-Galea, Diomedes E Logothetis, Aldo A Rodríguez-Menchaca

School of Pharmacy Faculty Articles

Phosphatidylinositol 4,5-bisphosphate (PIP2) is a membrane phospholipid that regulates the function of multiple ion channels, including some members of the voltage-gated potassium (Kv) channel superfamily. The PIP2 sensitivity of Kv channels is well established for all five members of the Kv7 family and for Kv1.2 channels; however, regulation of other Kv channels by PIP2 remains unclear. Here, we investigate the effects of PIP2 on Kv2.1 channels by applying exogenous PIP2 to the cytoplasmic face of excised membrane patches, activating muscarinic receptors (M1R), or depleting endogenous PIP2 using a rapamycin-translocated 5-phosphatase (FKBP-Inp54p). Exogenous PIP2 rescued Kv2.1 channels from rundown and partially …

Analysis Of Endocrine Response To Perceived Difference In Cross-Cultural Interactions, Carole Woolford-Hunt, Marlene Murray, Tevni Grajales Guerra, Kristina Beenken-Johnson

Faculty Publications

We live in a world where awareness of ethnic and cultural diversity is an ever increasing reality. Business and education turn to the social sciences to inform them about how to manage and optimize cross-cultural interactions. Although much research has been done on the impact of cross-cultural interactions on a wide range of variables, one less researched area is the endocrine response to cross-cultural interactions. In this study we set out to investigate the endocrine response to cross cultural interactions and the impact of these interactions on perceived differences. To do so we measured the pre and post levels of …

Dynamic Cycling Of T-Snare Acylation Regulates Platelet Exocytosis, Jinchao Zhang, Yunjie Huang, Jing Chen, Haining Zhu, Sidney W. Whiteheart

Molecular and Cellular Biochemistry Faculty Publications

Platelets regulate vascular integrity by secreting a host of molecules that promote hemostasis and its sequelae. Given the importance of platelet exocytosis, it is critical to understand how it is controlled. The t-SNAREs, SNAP-23 and syntaxin-11, lack classical transmembrane domains (TMDs), yet both are associated with platelet membranes and redistributed into cholesterol-dependent lipid rafts when platelets are activated. Using metabolic labeling and hydroxylamine (HA)/HCl treatment, we showed that both contain thioester-linked acyl groups. Mass spectrometry mapping further showed that syntaxin-11 was modified on cysteine 275, 279, 280, 282, 283, and 285, and SNAP-23 was modified on cysteine 79, 80, 83, …