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Other Pharmacy and Pharmaceutical Sciences Commons™
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Articles 1 - 8 of 8
Full-Text Articles in Other Pharmacy and Pharmaceutical Sciences
Structural Insights Into The Potency Of Sk Channel Positive Modulators, Young-Woo Nam, Razan Orfali, Tingting Liu, Kunqian Yu, Meng Cui, Heike Wulff, Miao Zhang
Structural Insights Into The Potency Of Sk Channel Positive Modulators, Young-Woo Nam, Razan Orfali, Tingting Liu, Kunqian Yu, Meng Cui, Heike Wulff, Miao Zhang
Pharmacy Faculty Articles and Research
Small-conductance Ca2+-activated K+ (SK) channels play essential roles in the regulation of cellular excitability and have been implicated in neurological and cardiovascular diseases through both animal model studies and human genetic association studies. Over the past two decades, positive modulators of SK channels such as NS309 and 1-EBIO have been developed. Our previous structural studies have identified the binding pocket of 1-EBIO and NS309 that is located at the interface between the channel and calmodulin. In this study, we took advantage of four compounds with potencies varying over three orders of magnitude, including 1-EBIO, NS309, SKS-11 (6-bromo-5-methyl-1H-indole-2,3-dione-3-oxime) and …
Role Of Microglial Amylin Receptors In Mediating Beta Amyloid (Aβ)-Induced Inflammation, Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David Mactavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas
Role Of Microglial Amylin Receptors In Mediating Beta Amyloid (Aβ)-Induced Inflammation, Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David Mactavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas
Pharmacy Faculty Articles and Research
Background: Neuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer’s disease (AD) pathology. Amyloid beta (Aβ) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Aβ activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors.
Methods: The presence of dimeric components of the amylin receptor (calcitonin receptor and receptor activity modifying protein 3) …
Trkb-Enhancer Facilitates Functional Recovery After Traumatic Brain Injury, John Marshall, Joanna Szmydynger-Chodobska, Mengia S. Rioult-Pedotti, Kara Lau, Andrea T. Chin, Siva K. Reddy Kotla, Rakesh Tiwari, Keykavous Parang, Steven W. Threlkeld, Adam Chodobski
Trkb-Enhancer Facilitates Functional Recovery After Traumatic Brain Injury, John Marshall, Joanna Szmydynger-Chodobska, Mengia S. Rioult-Pedotti, Kara Lau, Andrea T. Chin, Siva K. Reddy Kotla, Rakesh Tiwari, Keykavous Parang, Steven W. Threlkeld, Adam Chodobski
Pharmacy Faculty Articles and Research
Brain-derived neurotrophic factor (BDNF), a key player in regulating synaptic strength and learning, is dysregulated following traumatic brain injury (TBI), suggesting that stimulation of BDNF signaling pathways may facilitate functional recovery. This study investigates whether CN2097, a peptidomimetic ligand which targets the synaptic scaffold protein, postsynaptic density protein 95, to enhance downstream signaling of tropomyosin-related kinase B, a receptor for BDNF, can improve neurological function after TBI. Moderate to severe TBI elicits neuroinflammation and c-Jun-N-terminal kinase (JNK) activation, which is associated with memory deficits. Here we demonstrate that CN2097 significantly reduces the post-traumatic synthesis of proinflammatory mediators and inhibits the …
De Novo Triiodothyronine Formation From Thyrocytes Activated By Thyroid-Stimulating Hormone, Cintia E. Citterio, Balaji Veluswamy, Sarah J. Morgan, Valerie A. Galton, J. Paul Banga, Stephen Atkins, Yoshiaki Morishita, Susanne Neumann, Rauf Latif, Marvin C. Gershengorn, Terry J. Smith, Peter Arvan
De Novo Triiodothyronine Formation From Thyrocytes Activated By Thyroid-Stimulating Hormone, Cintia E. Citterio, Balaji Veluswamy, Sarah J. Morgan, Valerie A. Galton, J. Paul Banga, Stephen Atkins, Yoshiaki Morishita, Susanne Neumann, Rauf Latif, Marvin C. Gershengorn, Terry J. Smith, Peter Arvan
Pharmacy Faculty Articles and Research
The thyroid gland secretes primarily tetraiodothyronine (T4), and some triiodothyronine (T3). Under normal physiological circumstances, only one-fifth of circulating T3 is directly released by the thyroid, but in states of hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T3 toxicosis. Thyroidal T4 production results from iodination of thyroglobulin (TG) at residues Tyr5 and Tyr130, whereas thyroidal T3 production may originate in several different ways. In this study, the data demonstrate that within the carboxyl-terminal portion of mouse TG, T3 is formed …
Efficient Synthesis Of Cn2097 Using In Situ Activation Of Sulfhydryl Group, Shaban Darwish, Keykavous Parang, John Marshall, Dennis J. Goebel, Rakesh Tiwari
Efficient Synthesis Of Cn2097 Using In Situ Activation Of Sulfhydryl Group, Shaban Darwish, Keykavous Parang, John Marshall, Dennis J. Goebel, Rakesh Tiwari
Pharmacy Faculty Articles and Research
CN2097 (R7Cs-sCYK[KTE(β-Ala)]V) is a rationally designed peptidomimetic that shows effectiveness in preclinical models for the treatment of neurological disorders, such as Angelman syndrome, traumatic brain injury (TBI), and stroke. Because of its potential therapeutic activity for the treatment of human CNS disorders, there was an urgent need to develop an efficient strategy for large-scale synthesis of CN2097. The synthesis of CN2097 was accomplished using Fmoc/tBu solid phase chemistry in multiple steps. Two different peptide fragments (activated polyarginine peptide Npys-sCR7 and CYK[KTE(β-Ala)]V) were synthesized, followed by solution phase coupling in water. Activation of the polyarginine (CR7) …
Activity Of Distinct Growth Factor Receptor Network Components In Breast Tumors Uncovers Two Biologically Relevant Subtypes, Moom Roosan, Shelley M. Macneil, David F. Jenkins, Gajendra Shrestha, Sydney R. Wyatt, Jasmine A. Mcquerry, Stephen R. Piccolo, Laura M. Heiser, Joe W. Gray, W. Evan Johnson, Andrea H. Bild
Activity Of Distinct Growth Factor Receptor Network Components In Breast Tumors Uncovers Two Biologically Relevant Subtypes, Moom Roosan, Shelley M. Macneil, David F. Jenkins, Gajendra Shrestha, Sydney R. Wyatt, Jasmine A. Mcquerry, Stephen R. Piccolo, Laura M. Heiser, Joe W. Gray, W. Evan Johnson, Andrea H. Bild
Pharmacy Faculty Articles and Research
Background
The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns.
Methods
Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD). The pathway analysis toolkit Adaptive Signature Selection …
Actionable Patient Safety Solution (Apss) #3d: Pediatric Adverse Drug Events, Ron Jordan, Jerika Lam, Nathaniel Sims, Anne Lyren, Coco Yang
Actionable Patient Safety Solution (Apss) #3d: Pediatric Adverse Drug Events, Ron Jordan, Jerika Lam, Nathaniel Sims, Anne Lyren, Coco Yang
Pharmacy Faculty Articles and Research
This report presents a plan of action for introducing a "program to reduce the incidence of pediatric adverse drug events (pADEs) and harm ... [that] combine[s] leadership strategies, software (healthcare IT), hardware (drug compounding systems, drug delivery technology, and physiological monitoring systems), and most importantly people (changes in clinical practice, protocols and education)" to protect pediatric patients.
Actionable Patient Safety Solution (Apss) #3c: Improve Prevention Of Severe Hypoglycemia, Jerika Lam, Steven Barker, Michael Ramsay, Ariana Longley, Joe Kiani
Actionable Patient Safety Solution (Apss) #3c: Improve Prevention Of Severe Hypoglycemia, Jerika Lam, Steven Barker, Michael Ramsay, Ariana Longley, Joe Kiani
Pharmacy Faculty Articles and Research
This report presents a plan of action for introducing a "program to reduce errors in the recognition and treatment of [severe hypoglycemia]".