Medical Pharmacology Commons^™

Pediatric Hematology/Oncology Outpatient Care: The Effect Of A Standardized Collaborative Medication Reconciliation Process, Traci R. Pulliam

Evidence-Based Practice Project Reports

Pediatric patients are at an increased risk for medication errors and can benefit from processes that facilitate and promote medication safety (Stone et al., 2010). Medication reconciliation (Med Rec) is a valuable tool in improving patients’ medication safety and reducing adverse drug events (The Joint Commission, 2015). The purpose of this evidence-based practice (EBP) project was to improve the accuracy of the Med Rec process in a Midwestern pediatric hematology/oncology outpatient clinic by developing, promoting, and evaluating a standardized, collaborative Med Rec process. The Stetler EBP model guided the implementation of the intervention, with the goal of integrating current evidence …

Sigma1 Targeting To Suppress Aberrant Androgen Receptor Signaling In Prostate Cancer., Jeffrey D. Thomas, Charles G. Longen, Halley M. Oyer, Nan Chen, Christina M. Maher, Joseph M. Salvino, Blase Kania, Kelsey N. Anderson, William F. Ostrander, Karen E. Knudsen, Felix J. Kim

Department of Cancer Biology Faculty Papers

Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that …

Characterization Of A Mutant Oncolytic Adenovirus And The Role Of Jnk In Enhancing Virotherapy., Stephen L. Wechman

Electronic Theses and Dissertations

Oncolytic adenoviruses (Ads) have great therapeutic potential for lung cancer treatment. Cancer selective E1b-deleted Ads are safe; however, their clinical cancer therapeutic efficacy remains limited. The limited efficacy of Ad virotherapy is due to many factors including inefficient cancer cell lysis, Ad release and spread. Progress in overcoming these barriers to Ad virotherapy are hampered by limited knowledge of the genes associated with enhanced Ad release and spread and the dearth of understanding of the mechanisms by which E1b-deleted Ads cause cancer cell lysis. The role of c-JNK n- terminal kinase (JNK) phosphorylation in this process remains unknown. …

Characterization Of Novel Cannabinoid Receptor 2-Selective Agonists At The Biochemical And Cellular Levels: Leads For Therapeutic Agents, Ashley M. Hine

Honors Scholar Theses

Putative cannabinoid receptor 2 (CB₂)-selective agonists were identified from a library of commercially available compounds via inhibition of cAMP accumulation in high throughput screening. Binding affinity and receptor subtype selectivity were assessed using heterologous competition binding assays against the known cannabinoid orthosteric ligand CP55940. Test compounds ASX0152383 and CSC003141 preferentially bound to CB₂, with no detection of binding to CB₁ up to 1 mM. CMB038865 exhibited nearly 100-fold selectivity for CB₁ over CB₂, while CZ000026 bound non-preferentially to both receptors in the low micromolar range. To determine the extent of G protein …

Targeting The Glucose Metabolism Of Myeloid-Derived Suppressor Cells (Mdscs) To Stimulate Cancer Immunity., Jaspreet Grewal

Electronic Theses and Dissertations

Myeloid derived suppressor cells (MDSCs) are a heterogeneous group of immature myeloid cells that are significantly increased in cancer patients and correlate with higher stage and poor prognosis. MDSCs negatively modulate anti-tumor immunity, suppress T cell activity, promote angiogenesis and increase the risk of metastasis. In this study, we report that monocytic-MDSCs (M-MDSCs) but polymorphonuclear-MDSCs (PMN-MDSCs) over-express 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatases 3 (PFKFB3), an important regulator of glycolysis. Furthermore in the melanoma model, M-MDSCs but not PMN-MDSCs suppressed T cell function which correlated with PFKFB3 over-expression and increased rate of glycolysis. PFKFB3 inhibition with the first-in-class small molecule inhibitor, PFK-158 reversed M-MDSC …

Combating Malignant Melanoma With The Multifaceted Soy-Dervied Peptide Lunasin., Christopher Paul Shidal

Electronic Theses and Dissertations

Lunasin is a 44 amino acid peptide that has been shown to have cancer chemopreventative and chemotherapeutic properties. This study investigated the potential utility of Lunasin as a chemotherapeutic in melanomas. Studies showed that Lunasin had little activity against established melanoma cell lines using adherent culture methods; however, Lunasin’s in vitro activity was significantly higher in non-adherent colony-forming assays and oncosphere formation. These results led to the investigation of whether or not Lunasin has selective effects on cancer initiating cells (CIC) that are known to be present in melanomas. It was revealed that Lunasin selectively inhibited the proliferation of high-ALDH …

The Interaction Of Homoserine Lactones And Paraoxonase 2 Modulates Cell Death Signaling And Cell Proliferation., Aaron Mackallan Neely

Electronic Theses and Dissertations

Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule that functions to facilitate bacteria-bacteria communication. C12 has also been reported to affect many aspects of human host cell physiology, including evoking cell death in various types of cells. However, the signaling pathway(s) leading to C12-triggerred cell death remains unclear. To clarify cell death signaling induced by C12, we examined mouse embryonic fibroblasts (MEFs) deficient in one or more caspases. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in cells, probably through the direct induction of mitochondrial membrane permeabilization. Importantly, C12 induces apoptosis …

An Unusual Pulmonary Complication Of Statin Medication, Milliejoan Mongalo, Madhvi Shah, Lynne J. Goebel

Marshall Journal of Medicine

Statins or hydroxyl-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have proven efficacy at decreasing cardiovascular morbidity and mortality. Although statins have been prescribed safely, there should be more awareness of the possible adverse effects. Recently, we encountered a patient who had unexplained dyspnea, weakness, and immobility. The patient’s symptoms were alleviated after discontinuing the statin medication. Although we have no concrete evidence that her symptoms were due to the medication, the temporal relationship of symptom improvement upon discontinuation of the statin, led us to the conclusion that it could potentially have been the cause. Unexplained dyspnea is not listed as an …

Serial Deletion Reveals Structural Basis And Stability For The Core Enzyme Activity Of Human Glutaminase 1 Isoforms: Relevance To Excitotoxic Neurodegeneration., Yuju Li, Justin Peer, Runze Zhao, Yinghua Xu, Beiqing Wu, Yi Wang, Changhai Tian, Yunlong Huang, Jialin C. Zheng

Journal Articles: Pharmacology & Experimental Neuroscience

BACKGROUND: Glutaminase 1 is a phosphate-activated metabolic enzyme that catalyzes the first step of glutaminolysis, which converts glutamine into glutamate. Glutamate is the major neurotransmitter of excitatory synapses, executing important physiological functions in the central nervous system. There are two isoforms of glutaminase 1, KGA and GAC, both of which are generated through alternative splicing from the same gene. KGA and GAC both transcribe 1-14 exons in the N-terminal, but each has its unique C-terminal in the coding sequence. We have previously identified that KGA and GAC are differentially regulated during inflammatory stimulation and HIV infection. Furthermore, glutaminase 1 has …

Constitutive Activation Of Kappa Opioid Receptors At Ventral Tegmental Area Inhibitory Synapses Following Acute Stress., Abigail M Polter, Kelsey Barcomb, Rudy W Chen, Paige M Dingess, Nicholas M Graziane, Travis E Brown, Julie A Kauer

Pharmacology and Physiology Faculty Publications

Stressful experiences potently activate kappa opioid receptors (κORs). κORs in the ventral tegmental area regulate multiple aspects of dopaminergic and non-dopaminergic cell function. Here we show that at GABAergic synapses on rat VTA dopamine neurons, a single exposure to a brief cold-water swim stress induces prolonged activation of κORs. This is mediated by activation of the receptor during the stressor followed by a persistent, ligand-independent constitutive activation of the κOR itself. This lasting change in function is not seen at κORs at neighboring excitatory synapses, suggesting distinct time courses and mechanisms of regulation of different subsets of κORs. We also …

Short-Term Bilateral Adrenalectomy: Biochemical And Morphological Alterations In The Rat Hippocampus, Ahlam Said Abi Issa

Theses

Several studies showed the effects of glucocorticoid hormones on the hippocampus. It has been reported that the chronic administration of high dose glucocorticoids (GC) results in the degeneration of pyramidal neurons. However, bilateral adrenalectomy has been shown to damage the hippocampal neurons. Although the effects of long-term adrenalectomy have been studied extensively, there are few publications on the effects of short-term bilateral adrenalectomy (ADX). We aimed to investigate the effects of ADX on levels of pro-inflammatory cytokines interleukin-1β (IL-1β), interkeukin-6 (IL-6) and tumor necrosis factor-α (TNF-α); levels of growth factors, response of microglia and astrocytes to neuronal death, and oxidative …

A Rare Case Of Vascular Ring And Coarctation Of The Aorta In Association With Charge Syndrome., Jonathan B. Wagner, Joshua Q. Knowlton, Peter Pastuszko, Sanket Shah

Manuscripts, Articles, Book Chapters and Other Papers

A male neonate presented with CHARGE syndrome, a multiorgan genetic disorder involving the Coloboma of the eyes, congenital Heart defects, nasal choanal Atresia, growth and development Retardation, Genitourinary disorders, and Ear anomalies and deafness. Moreover, he had a rare case of vascular ring-consisting of a right aortic arch with retroesophageal brachiocephalic artery-combined with coarctation of the mid-aortic arch. He underwent both vascular ring and aortic arch repair at our institution. To our knowledge, this is the 4th documented case of this exceedingly rare type of aortic arch anomaly combined with aortic arch obstruction. Moreover, it is the first confirmed case …

Impact Of Cyp2d6 Genotype On Amitriptyline Efficacy For The Treatment Of Diabetic Peripheral Neuropathy: A Pilot Study., Mamoonah Chaudhry, Marco Alessandrini, Jacobus Rademan, Tyren M. Dodgen, Francois E. Steffens, Danie G. Van Zyl, Andrea Gaedigk, Michael S. Pepper

Manuscripts, Articles, Book Chapters and Other Papers

AIM: Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles.

METHOD: To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced.

RESULTS: Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity.

CONCLUSION: Hence, CYP2D6 genotype contributes to …

In Vivo Characterization Of Cyp2d6*12, *29 And *84 Using Dextromethorphan As A Probe Drug: A Case Report., Andrea Gaedigk, Greyson P. Twist, Emily G. Farrow, Jennifer Lowry, Sarah E. Soden, Neil A. Miller

Manuscripts, Articles, Book Chapters and Other Papers

CYP2D6*84 was first described in a Black South African subject, however, its function remains unknown. Astrolabe, a probabilistic scoring tool developed in our laboratory to call genotypes from whole genome sequence, identified CYP2D6*84 in a trio. The father presented with intermediate metabolism when challenged with the CYP2D6 probe drug dextromethorphan (DM/dextrorphan [DX] = 0.0839). Since his second allele, CYP2D6*12, is nonfunctional, the observed activity is derived by CYP2D6*84. This finding suggests that the allele's hallmark P267H causes decreased activity toward DM and that this allele should receive a value of 0.5 for Activity Score calculations. The mother's DM/DX of 0.0543 …

Enzyme-Dependent Fluorescence Recovery Of Nadh After Photobleaching To Assess Dehydrogenase Activity Of Isolated Perfused Hearts., Angel Moreno, Sarah Kuzmiak-Glancy, Rafael Jaimes, Matthew W Kay

Pharmacology and Physiology Faculty Publications

Reduction of NAD(+) by dehydrogenase enzymes to form NADH is a key component of cellular metabolism. In cellular preparations and isolated mitochondria suspensions, enzyme-dependent fluorescence recovery after photobleaching (ED-FRAP) of NADH has been shown to be an effective approach for measuring the rate of NADH production to assess dehydrogenase enzyme activity. Our objective was to demonstrate how dehydrogenase activity could be assessed within the myocardium of perfused hearts using NADH ED-FRAP. This was accomplished using a combination of high intensity UV pulses to photobleach epicardial NADH. Replenishment of epicardial NADH fluorescence was then imaged using low intensity UV illumination. NADH …

Proteome Dynamics During Postnatal Mouse Corpus Callosum Development., Alexander I Son, Xiaoqin Fu, Fumikazu Suto, Judy S Liu, Kazue Hashimoto-Torii, Masaaki Torii

Pharmacology and Physiology Faculty Publications

Formation of cortical connections requires the precise coordination of numerous discrete phases. This is particularly significant with regard to the corpus callosum, whose development undergoes several dynamic stages including the crossing of axon projections, elimination of exuberant projections, and myelination of established tracts. To comprehensively characterize the molecular events in this dynamic process, we set to determine the distinct temporal expression of proteins regulating the formation of the corpus callosum and their respective developmental functions. Mass spectrometry-based proteomic profiling was performed on early postnatal mouse corpus callosi, for which limited evidence has been obtained previously, using stable isotope of labeled …

Metabolic And Molecular Insights Into An Essential Role Of Nicotinamide Phosphoribosyltransferase., Li Q. Zhang, Leon Van Haandel, Min Xiong, Peixin Huang, Daniel P. Heruth, Chengpeng Bi, R Gaedigk, Xun Jiang, Ding-You Li, Gerald Wyckoff, Dmitry N. Grigoryev, Li Gao, Linheng Li, Min Wu, J Steven Leeder, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of NAMPT in these physiological and pathological processes are not fully understood. Here, we provide experimental evidence that a Nampt gene homozygous knockout (Nampt-/-) resulted in lethality at an early stage of mouse embryonic development and death within 5-10 days in adult mice accompanied by a 25.24±2.22% body weight loss, after the tamoxifen induction of NamptF/F × Cre mice. These results substantiate that Nampt …

Role Of Cytokines And Chemokines In Alcohol-Induced Tumor Promotion, Danlei Chen, Fengyun Zhang, Haifeng Ren, Jia Luo, Siying Wang

Pharmacology and Nutritional Sciences Faculty Publications

Excessive chronic alcohol consumption has become a worldwide health problem. The oncogenic effect of chronic alcohol consumption is one of the leading concerns. The mechanisms of alcohol-induced tumorigenesis and tumor progression are largely unknown, although many factors have been implicated in the process. This review discusses the recent progress in this research area with concentration on alcohol-induced dysregulation of cytokines and chemokines. Based on the available evidence, we propose that alcohol promotes tumor progression by the dysregulation of the cytokine/chemokine system. In addition, we discuss specific transcription factors and signaling pathways that are involved in the action of these cytokines/chemokines …

A Role Of Central Nell2 In The Regulation Of Feeding Behavior In Rats., Jin Kwon Jeong, Jae Geun Kim, Han Rae Kim, Tae Hwan Lee, Jeong Woo Park, Byung Ju Lee

Pharmacology and Physiology Faculty Publications

A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes …

Mammary Epithelial Polarity And Macrophage Infiltration, Ren Xu

Pharmacology and Nutritional Sciences Faculty Publications

Loss of epithelial cell polarity and inflammation are hallmarks of breast cancer development. Although the association between the disruption of tissue polarity and inflammation has been demonstrated, we know little about how these two events are coupled. Using the 3D co-culture model of mammary epithelial cells and monocytes, a recent study reveals a link between disruption of epithelial polarity and monocytes infiltration.

A Mature Macrophage Is A Principal Hiv-1 Cellular Reservoir In Humanized Mice After Treatment With Long Acting Antiretroviral Therapy., Mariluz Araínga, Benson J. Edagwa, R. Lee Mosley, Larisa Y. Poluektova, Santhi Gorantla, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

BACKGROUND: Despite improved clinical outcomes seen following antiretroviral therapy (ART), resting CD4+ T cells continue to harbor latent human immunodeficiency virus type one (HIV-1). However, such cells are not likely the solitary viral reservoir and as such defining where and how others harbor virus is imperative for eradication measures. To such ends, we used HIV-1ADA-infected NOD.Cg-Prkdc (scid) Il2rg (tm1Wjl) /SzJ mice reconstituted with a human immune system to explore two long-acting ART regimens investigating their abilities to affect viral cell infection and latency. At 6 weeks of infection animals were divided into four groups. One received long-acting (LA) cabotegravir (CAB) …

Extensions Of D-Optimal Minimal Designs For Symmetric Mixture Models., Yanyan Li, Damaraju Raghavarao, Inna Chervoneva

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The purpose of mixture experiments is to explore the optimum blends of mixture components, which will provide desirable response characteristics in finished products. D-optimal minimal designs have been considered for a variety of mixture models, including Scheffé's linear, quadratic, and cubic models. Usually, these D-optimal designs are minimally supported since they have just as many design points as the number of parameters. Thus, they lack the degrees of freedom to perform the Lack of Fit tests. Also, the majority of the design points in D-optimal minimal designs are on the boundary: vertices, edges, or faces of the design simplex.

IN …

Chemogenetic Stimulation Of The Hypoglossal Neurons Improves Upper Airway Patency, Thomas Curado, Kenneth Fishbein, Huy Pho, Michael Brennick, Olga Dergacheva, David Mendelowitz, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of OSA has been linked to a defect in neuromuscular control of the pharynx. There is no effective pharmacotherapy for OSA. The objective of this study was to determine whether upper airway patency can be improved using chemogenetic approach by deploying designer receptors exclusively activated by designer drug (DREADD) in the hypoglossal motorneurons. DREADD (rAAV5-hSyn-hM3(Gq)-mCherry) and control virus (rAAV5-hSyn-EGFP) were stereotactically administered to the hypoglossal nucleus of C57BL/6J mice. In 6–8 weeks genioglossus EMG and dynamic MRI …

Oxidative Stress-Driven Parvalbumin Interneuron Impairment As A Common Mechanism In Models Of Schizophrenia, P Steullet, J Cabungcal, J Coyle, M Didriksen, K Gill, Anthony-Samuel Lamantia, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant …

Clinical Pharmacology & Therapeutics: Past, Present, And Future., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Clinical Pharmacology & Therapeutics (CPT), the definitive and timely source for advances in human therapeutics, transcends the drug discovery, development, regulation, and utilization continuum to catalyze, evolve, and disseminate discipline-transformative knowledge. Prioritized themes and multidisciplinary content drive the science and practice of clinical pharmacology, offering a trusted point of reference. An authoritative herald across global communities, CPT is a timeless information vehicle at the vanguard of discovery, translation, and application ushering therapeutic innovation into modern healthcare.

Identification And Characterization Of Microrna Differentially Expressed In Macrophages Exposed To Porphyromonas Gingivalis Infection, Olivier Huck, J Al-Hashemi, L Poidevin, O Poch, J Davideau, H Tenenbaum, Salomon Amar

NYMC Faculty Publications

MicroRNAs (miRNAs) are short, noncoding RNAs involved in the regulation of several processes associated with inflammatory diseases and infection. Bacterial infection modulates miRNA expression to subvert any innate immune response. In this study we analyzed, using microarray analysis, the bacterial modulation of miRNAs in bone marrow-derived macrophages (BMMs) in which activity was induced by infection with Porphyromonas gingivalis The expression of several miRNAs was modulated 3 h postinfection (at a multiplicity of infection of 25). A bioinformatic analysis was performed to further identify pathways related to the innate immune host response under the influence of selected miRNAs. To assess the …

Topical Anaesthetics For Pain Control During Repair Of Dermal Laceration., Baraa O. Tayeb, Anthony Eidelman, Cristy L. Eidelman, Ewan D. Mcnicol, Daniel B. Carr

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Topical local anaesthetics provide effective analgesia for patients undergoing numerous superficial procedures, including repair of dermal lacerations. The need for cocaine in topical anaesthetic formulations has been questioned because of concern about adverse effects, thus novel preparations of cocaine-free anaesthetics have been developed. This review was originally published in 2011 and has been updated in 2017.

OBJECTIVES: To assess whether benefits of non-invasive topical anaesthetic application occur at the expense of decreased analgesic efficacy. To compare the efficacy of various single-component or multi-component topical anaesthetic agents for repair of dermal lacerations. To determine the clinical necessity for topical application …

Dub3 Inhibition Suppresses Breast Cancer Invasion And Metastasis By Promoting Snail1 Degradation, Yadi Wu, Yu Wang, Yiwei Lin, Yajuan Liu, Yifan Wang, Jianhang Jia, Puja Singh, Young-In Chi, Chi Wang, Chenfang Dong, Wei Li, Min Tao, Dana L. Napier, Qiuying Shi, Jiong Deng, B. Mark Evers, Binhua P. Zhou

Pharmacology and Nutritional Sciences Faculty Publications

Snail1, a key transcription factor of epithelial–mesenchymal transition (EMT), is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumours remains unclear. We identify Dub3 as a bona fide Snail1 deubiquitinase, which interacts with and stabilizes Snail1. Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis. These effects are rescued by ectopic Snail1 expression. IL-6 also stabilizes Snail1 by inducing Dub3 expression, the specific inhibitor WP1130 binds to Dub3 and inhibits the Dub3-mediating Snail1 stabilization in vitroand in vivo. …

M2 Polarization Of Macrophages Facilitates Arsenic-Induced Cell Transformation Of Lung Epithelial Cells, Jiajun Cui, Wenhua Xu, Jian Chen, Hui Li, Lu Dai, Jacqueline A. Frank, Shaojun Peng, Siying Wang, Gang Chen

Pharmacology and Nutritional Sciences Faculty Publications

The alterations in microenvironment upon chronic arsenic exposure may contribute to arsenic-induced lung carcinogenesis. Immune cells, such as macrophages, play an important role in mediating the microenvironment in the lungs. Macrophages carry out their functions after activation. There are two activation status for macrophages: classical (M1) or alternative (M2); the latter is associated with tumorigenesis. Our previous work showed that long-term arsenic exposure induces transformation of lung epithelial cells. However, the crosstalk between epithelial cells and macrophages upon arsenic exposure has not been investigated. In this study, using a co-culture system in which human lung epithelial cells are cultured with …

Genetic Targeting In Cerebellar Purkinje Cells: An Update., Anna Sługocka, Jan Wiaderkiewicz, Jaroslaw J Barski

Pharmacology and Physiology Faculty Publications

Since the last review paper published in Cerebellum in 2002 [1], there has been a substantial increase in the number of experiments utilizing transgenic manipulations in murine cerebellar Purkinje cells. Most of these approaches were made possible with the use of the Cre/loxP methodology and pcp2/L7 based Cre recombinase expressing transgenic mouse strains. This review aims to summarize all studies which used Purkinje cell specific transgenesis since the first use of mouse strain with Purkinje cell specific Cre expression in 2002.