Pharmacy and Pharmaceutical Sciences Commons^™

Tgf-Β Neutralization Enhances Angii-Induced Aortic Rupture And Aneurysm In Both Thoracic And Abdominal Regions, Xiaofeng Chen, Debra L. Rateri, Deborah A. Howatt, Anju Balakrishnan, Jessica J. Moorleghen, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

AngII and TGF-β interact in development of thoracic and abdominal aortic diseases, although there are many facets of this interaction that have not been clearly defined. The aim of the present study was to determine the effects of TGF-β neutralization on AngII induced-aortic pathologies. Male C57BL/6J mice were administered with either a rabbit or mouse TGF-β neutralizing antibody and then infused with AngII. The rabbit TGF-β antibody modestly reduced serum TGF-β concentrations, with no significant enhancements to AngII-induced aneurysm or rupture. Administration of this rabbit TGF-β antibody in mice led to high serum titers against rabbit IgG that may have …

Almond Supplementation Reduces Serum Uric Acid In Coronary Artery Disease Patients: A Randomized Controlled Trial., Humaira Jamshed, Anwar Gilani, Fateh Ali Tipoo Sultan, Faridah Amin, Jamshed Arslan Arslan, Sumaira Ghani, Madiha Masroor

Department of Biological & Biomedical Sciences

Objective

Elevated serum uric acid (UA), a biomarker of renal insufficiency, is also an independent prognostic marker for morbidity in coronary artery disease (CAD) and poses serious health risks. This study reports the effect of almond consumption on UA in CAD patients.

Study design

A randomized controlled clinical trial was conducted with three groups: no-intervention (NI), Pakistani almonds (PA) or American almonds (AA). Patients were recruited from the Cardiology Clinics, Aga Khan University Hospital. Two follow-ups were scheduled at week-6 and week-12. 150 patients were randomly divided in three groups (50 per group). NI was not given almonds, whereas the …

Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, Peican Zhu, Hamidreza Montazeri Aliabadi, Hasan Uludag, Jie Han

Pharmacy Faculty Articles and Research

The investigation of vulnerable components in a signaling pathway can contribute to development of drug therapy addressing aberrations in that pathway. Here, an original signaling pathway is derived from the published literature on breast cancer models. New stochastic logical models are then developed to analyze the vulnerability of the components in multiple signalling sub-pathways involved in this signaling cascade. The computational results are consistent with the experimental results, where the selected proteins were silenced using specific siRNAs and the viability of the cells were analyzed 72 hours after silencing. The genes elF4E and NFkB are found to have nearly no …

Design, Synthesis, And Evaluation Of Chitosan Conjugated Ggrgdsk Peptides As A Cancer Cell-Targeting Molecular Transporter, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Magda Goda El-Meligy, Ahmed Kamel El-Ziaty, Zenat A. Nagieb, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Targeting cancer cells using integrin receptor is one of the promising targeting strategies in drug delivery. In this study, we conjugated an integrin-binding ligand (GGRGDSK) peptide to chitosan oligosaccharide (COS) using (sulfo-SMCC) bifunctional linker affording COS-SMCC-GGRGDSK. The conjugated polymer was characterized by FT-IR, ¹H NMR, ¹³C NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1 mg/mL in the human leukemia cell line (CCRF-CEM). The conjugate was evaluated for its ability to enhance the cellular uptake of cell-impermeable cargoes (e.g., FAM and F′-G(pY)EEI phosphopeptide) in CCRF-CEM, and human ovarian carcinoma (SK-OV-3) cancer …

Optimizing Guideline-Recommended Antibiotic Doses For Pediatric Infective Endocarditis, Chad A. Knoderer, Kristen R. Nichols, Emily N. Israel, Christopher A. Thomas

Scholarship and Professional Work – COPHS

The American Heart Association recently published an updated scientific statement on the management of infective endocarditis in childhood. The recommendations included for vancomycin, aminoglycoside, and β-lactam dosing and monitoring are based primarily on expert opinion and do not consider available evidence for dose optimization based on pharmacokinetic and pharmacodynamic principles in pediatric patients. This is concerning because even when clinically necessary, some practitioners may be hesitant to deviate from guideline-recommended doses. In this perspective, we highlight potential areas for improvement in the statement-recommended doses and summarize evidence supporting antibiotic dosing optimization. The addition of a pediatric clinical pharmacist with expertise …

Modeling Of Ambient Glutamate Concentration Measurement In The Mammalian Nervous System, Denis M. Shchepakin, Michael Kavanaugh, Leonid Kalachev

Biomedical and Pharmaceutical Sciences Faculty Publications

A neuron is an electrically excitable cell that processes and transmits information through electrical and chemical signals. Neurons connect and pass signals to other cells through the structure called synapse. We focus on synapses through which the signals are transferred by signaling molecules called neurotransmitters. One of the predominant excitatory neurotransmitters in the central nervous system of the mammals, including humans, is glutamate. It is directly or indirectly involved in most brain functions. However, the excessive stimulation of the glutamate receptors is toxic to neurons, therefore it is important to rapidly clear the glutamate from the extra-cellular space and keep …

D-Serine Is A Substrate For Neutral Amino Acid Transporters Asct1/Slc1a4 And Asct2/Slc1a5, And Is Transported By Both Subtypes In Rat Hippocampal Astrocyte Cultures, Alan C. Foster, Jill Farnsworth, Genevieve Lind, Yong-Xin Lin, Jia-Ying Yang, Van Dang, Mahmud Penjwini, Veena Viswanath, Ursula Staubli, Michael Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

N-methyl-D-aspartate (NMDA) receptors play critical roles in synaptic transmission and plasticity. Activation of NMDA receptors by synaptically released L-glutamate also requires occupancy of co-agonist binding sites in the tetrameric receptor by either glycine or D-serine. Although D-serine appears to be the predominant co-agonist at synaptic NMDA receptors, the transport mechanisms involved in D-serine homeostasis in brain are poorly understood. In this work we show that the SLC1 amino acid transporter family members SLC1A4 (ASCT1) and SLC1A5 (ASCT2) mediate homo- and hetero-exchange of D-serine with physiologically relevant kinetic parameters. In addition, the selectivity profile of D-serine uptake in cultured rat hippocampal …

Whole Genome Sequence Analysis Of The Tallyho/Jng Mouse, James Denvir, Goran Boskovic, Jun Fan, Donald A. Primerano, Jacaline K. Parkman, Jung Han Kim

Biochemistry and Microbiology

Background: The TALLYHO/Jng (TH) mouse is a polygenic model for obesity and type 2 diabetes first described in the literature in 2001. The origin of the TH strain is an outbred colony of the Theiler Original strain and mice derived from this source were selectively bred for male hyperglycemia establishing an inbred strain at The Jackson Laboratory. TH mice manifest many of the disease phenotypes observed in human obesity and type 2 diabetes.

Results: We sequenced the whole genome of TH mice maintained at Marshall University to a depth of approximately 64.8X coverage using data from three next generation sequencing …

Ovarian Tumour Growth Is Characterized By Mevalonate Pathway Gene Signature In An Orthotopic, Syngeneic Model Of Epithelial Ovarian Cancer, Daniel B. Hardy

Physiology and Pharmacology Publications

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer and often is not detected until late stages when cancer cells transcoelomically metastasize to the abdomen and typically become resistant to therapy resulting in very low survival rates. We utilize an orthotopic, syngeneic mouse model to study late stage disease and have discovered that the tumor cells within the abdominal ascites are irreversibly re-programmed, with an increased tumorigenicity and resistance to apoptosis. The goal of this study was to characterize the reprogramming that occurred in the aggressive ascites-derived cells (28-2 cells) compared to the original cell line used for tumor …

Nicotine Directly Induces Endoplasmic Reticulum Stress Response In Rat Placental Trophoblast Giant Cells, Michael K. Wong, Alison Holloway C, Daniel B. Hardy

Physiology and Pharmacology Publications

Nicotine exposure during pregnancy leads to placental insufficiency impairing both fetal and neonatal development. Previous studies from our laboratory have demonstrated that in rats,nicotine augmented endoplasmic reticulum (ER) stress in association with placental insufficiency, however, the underlying mechanisms remain elusive. Therefore, we sought to investigate the possible direct effect of nicotine on ER stress in Rcho-1 rat placental trophoblastgiant (TG) cells during differentiation. Protein and/or mRNA expression of markers involved in ER stress (e.g., phosphorylated PERK, eIF2α, CHOP, BiP/GRP78) and trophoblast giant cell differentiation and function (e.g., Pl-1, Pgf, Hsd11b1, and Hsd11b2) were quantified via Western blot or …

Pharmacogenomic Management Of Familial Hypercholesterolemia: An Integrative Review Of The Literature, Brian V. Skibo

Honors Undergraduate Theses

The purpose of this thesis is to examine familial hypercholesterolemia (FH) and emerging pharmacogenomics therapies that propose to lower serum low density lipid (LDL) levels. The search of various data bases resulted in nine research articles being selected for review. Syntheses of the articles suggest emerging phamacogenomic drug therapy can improve treatment outcomes for individuals with a diagnosis of FH. The Human Genome Project (HGP) has had far reaching applications for genomic technologies and pharmacagenomic interventions, tailored to human conditions associated with select genomic traits. Synthesis of nine research articles demonstrate that little is known on the topic and reveals …

Capillary Endothelia From Two Adpkd Patients Are Polyploidy, Sarmed H. Kathem, Wissam A. Aboualaiwi, Xiaolin Zi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Bilateral renal cyst formation is the main feature of autosomal dominant polycystic kidney disease (ADPKD). We and other laboratories have previously shown that cystlining epithelia of kidneys from ADPKD patients are characterized by polyploidy. In this report, we show that endothelia from the renal capillary beds of two ADPKD patients are also polyploidy. Spectral karyotyping study further confirms our flow cytometry analyses. We suggest that polyploidy may be used as a potential cellular marker in ADPKD.

Epigenetic Modification Prevents Excessive Wound Healing And Scar Formation After Glaucoma Filtration Surgery, Ajay Sharma, Govindaraj Anumanthan, Marcos Reyes, Huiyi Chen, Jason W. Brubaker, Saad Siddiqui, Suneel Gupta, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. The purpose of this study was to determine the efficacy of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), in prevention of excessive wound healing and scar formation in a rabbit model of glaucoma filtration surgery (GFS).

METHODS. A rabbit model of GFS was used. Rabbits that underwent GFS received balanced salt solution, or SAHA (50 lM), or mitomycin C (0.02%). Clinical scores of IOP, bleb vascularity, and slit-lamp examination were performed. On postoperative day 14, rabbits were killed and the bleb tissues were collected for evaluation of tissue fibrosis with hematoxylin and eosin, Masson trichrome, a-smooth muscle …

Novel Cellular Targets Of Aspirin In Chemoprevention Studies On P53, G6pd And C-Myc, Guoqiang Ai

Electronic Theses and Dissertations

Background

Aspirin has generated a significant interest in recent years as a potential chemopreventive agent supported by strong evidence from epidemiological data; however, the mechanisms are not well understood. The objective of this dissertation is to identify novel cyclooxygenase (COX)-independent pathways by which aspirin exerts its anticancer effects in epithelial cancer cell lines. We investigated the effect of aspirin on p53, glucose 6-phosphate dehydrogenase (G6PD), and c-Myc, all of which are known to play a major role in cancer development. p53 is a tumor suppressor protein, often mutated in cancers causing its inactivation. Expression of G6PD is elevated in many …

Development Of A Novel In Vivo Corneal Fibrosis Model In The Dog, K. M. Gronkiewicz, Elizabeth A. Giuliano, K. Kuroki, F. Bunyak, Ajay Sharma, L. B. C. Teixeira, C. W. Hamm, R. R. Mohan

Pharmacy Faculty Articles and Research

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading …

Molecular Mechanisms Of Suberoylanilide Hydroxamic Acid In The Inhibition Of Tgf-Β1-Mediated Canine Corneal Fibrosis, Kristina M. Gronkiewicz, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To investigate molecular mechanisms mediating anti-fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad-dependent and, to a lesser extent, Smad-independent signaling pathways activated by TGF-β1, as well as matrix metalloproteinase (MMP) activity.

Methods—Cultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF-β1 (5ng/ml) and SAHA (2.5μM) for 24hrs. Western blot analysis was used to quantify non-phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2 and JNK1. Real-time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8 and MMP9 mRNA expression and …

Characterization Of Inhibitor Of Differentiation (Id) Proteins In Human Cornea, Rajiv R. Mohan, Brandie R. Morgan, Govinduraj Anumanthan, Ajay Sharma, Shyam S. Chaurasia, Frank G. Rieger

Pharmacy Faculty Articles and Research

Inhibitor of differentiation (Id) proteins are DNA-binding transcription factors involved in cellular proliferation, migration, inflammation, angiogenesis and fibrosis. However, their expression and role in the cornea is unknown. The present study was undertaken to characterize the expression of Id proteins and their interactions with the pro-fibrotic cytokine Transforming Growth Factor β1 (TGFβ1) and anti-fibrotic cytokine, bone morphogenic protein 7 (BMP7) in human cornea. Human donor corneas procured from Eye Bank were used. Id proteins were localized in human corneal sections using immunofluorescence. Primary cultures of human corneal fibroblasts (HCF) were established and treated with either TGFβ1 (5 ng/ml) or BMP7 …

Rapamycin Rescues Vascular, Metabolic And Learning Deficits In Apolipoprotein E4 Transgenic Mice With Pre-Symptomatic Alzheimer’S Disease, Ai-Ling Lin, Jordan B. Jahrling, Wei Zhang, Nicholas Derosa, Vikas Bakshi, Peter Romero, Veronica Galvan, Arlan Richardson

Sanders-Brown Center on Aging Faculty Publications

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood–brain barrier integrity and glucose metabolism, compared …

Development Of Oral Vaccines Against Lyme Disease, Rita Raquel Dos Anjos De Carvalho E Melo

Theses and Dissertations (ETD)

Lyme Disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. If left untreated, it can lead to permanent damage to the nervous and musculoskeletal systems. In some cases, patients that receive the recommended antibiotic therapy develop a debilitating health condition associated with substantial health care costs. Despite current preventive measures, the incidence and the geographic distribution of Lyme Disease continues to increase. Recent estimates from CDC suggest that the true number of cases of Lyme Disease in the US is approximately 300,000 per year. Yet, there is currently no vaccine …

Development And Evaluation Of Amphotericin B Loaded Iron Oxide Nanoparticles For Targeted Drug Delivery To Systemic Fungal Infections, Pavan Balabathula

Theses and Dissertations (ETD)

A targeted nanotheronostic drug delivery system to diagnose and treat life threatening invasive fungal infections (IFIs) such as cryptococcal meningitis was designed, developed, characterized, and evaluated. To address the development processes, first, iron oxide nanoparticles (IONP) (34-40 nm) coated with bovine serum albumin (BSA), loaded and targeted with amphotericin B (AMB) (AMB-IONP) was formulated by applying a layer by layer approach. Several designs (A, B, C, D, & E) of AMB-IONP were developed and their physicochemical properties such as drug loading with HPLC method, particle size, poly dispersity index (PDI), and ζ-potential using dynamic light scattering (DLS) technique, morphology with …

Pharmacists On The Front Lines Of Polypharmacy: The Individualized Medication Assessment And Planning (Imap) Project To Improve Medication Use In Senior Adults With Cancer, Ginah Nightingale Pharmd, Bcop, Laura T. Pizzi Pharmd, Mph, Emily Hajjar Pharmd, Bcps, Bcacp, Cgp, Elizabeth Pigott, Margaret Wang, Shannon Doherty, Kristine Swartz Md, Andrew Chapman Do, Facp

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

A Phase I Study Of Ad5-Gucy2c-Padre In Stage I And Ii Colon Cancer Patients, Adam E. Snook, Trevor R. Baybutt, Michael J. Mastrangelo, Nancy L. Lewis, Scott D. Goldstein, Walter K. Kraft, Yaa D. Oppong, Terry Hyslop, Ronald E. Myers, Vitali Alexeev, Laurence C. Eisenlohr, Takami Sato, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Posters

Background

Ad5-GUCY2C-PADRE is a replication-deficient human type 5 recombinant adenovirus (Ad5) vaccine encoding guanylyl cyclase C (GUCY2C) fused to the PAn DR Epitope (PADRE). GUCY2C, a paracrine hormone receptor producing the second messenger cyclic GMP (cGMP), is selectively expressed by intestinal epithelial cells and a subset of hypothalamic neurons, but not other tissues. Importantly, GUCY2C is over-expressed in nearly all primary and metastatic human colorectal tumors. Preclinical studies in mice demonstrated selective tolerance of GUCY2C-specific CD4+ T cells, but not CD8+ T or B cells, necessitating inclusion of the exogenous CD4+ T helper cell epitope PADRE to maximize GUCY2C-specific CD8+ …

Regulating Drug Promotion To Promote The Public Health: A Response To Bennett, Et Al., Patricia J. Zettler

Faculty Publications By Year

No abstract provided.

Compatibility Of Vancomycin And Oxacillin During Simulated Y-Site Delivery, Chad A. Knoderer, Hilary M. Teibel, Kristen R. Nichols

Scholarship and Professional Work – COPHS

Background: Vancomycin and oxacillin may be used together as empiric coverage in patients with proven or suspected Staphylococcus aureus infections. Though vancomycin hydrochloride 20 mg/mL and oxacillin sodium 160 mg/mL are reported to be compatible via Y-site delivery, Y-site compatibility of commonly used concentrations, vancomycin 10 mg/mL and oxacillin 20 mg/mL, has not yet been reported. Objective: To determine the Y-site compatibility of vancomycin 10 mg/mL and oxacillin 20 mg/mL. Methods: One vancomycin hydrochloride 1 g vial was reconstituted with 10 mL sterile water for injection (SWFI) and diluted with 90 mL 5% dextrose in water (D5W) …

Temporal And Spatial Changes In The Pattern Of Iba1 And Cd68 Staining In The Rat Brain Following Severe Traumatic Brain Injury, Debbie Smith, Diane Brooks, Eric Wohlgehagen, Thomas Rau, David Poulsen

Biomedical and Pharmaceutical Sciences Faculty Publications

We have previously demonstrated that acute treatment with low dose methamphetamine is neuroprotectivein a rat model of severe traumatic brain injury (TBI). Using gene expression analysis, we further showed that methamphetamine treatment significantly reduced the expression of proinflammatory genes after severe TBI. Therefore, to further investigate the potential effects of methamphetamine treatment on the neuroinflammatory response, we examined immunofluorescent staining of Iba1 and CD68, two marker of neuroinflammation, in the rat lateral fluid percussion injury model of severe TBI. In this study, we observed temporal and spatial alterations in the pattern of Iba1 and CD68 labeling within two weeks after …

Higher Hepatic Mir-29 Expression In Undernourished Male Rats During The Postnatal Period Targets The Long-Term Repression Of Insulin-Like Growth Factor 1, Gurjeev Sohi, Andrew Revesz, Julie Ramkumar, Daniel B. Hardy

Physiology and Pharmacology Publications

A nutritional mismatch in postnatal life of low birth weight offspring increases the risk of developing the metabolic syndrome. Moreover, this is associated with decreased hepatic insulin-like growth factor 1 (Igf1) expression, leading to impaired growth and metabolism. Previously we have demonstrated that the timing of nutritional restoration in perinatal life can differentially programhepatic gene expression. While micro RNAs also play an important role in silencing gene expression, to date, the impact of a nutritional mismatch in neonatal life on their long-term expression has not been evaluated. Given the complementarity of miR-29 to the 3i-UTR of Igf1, we examined how …

Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg

Pharmacy Faculty Articles and Research

Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro …

Cerium Oxide Nanoparticles Inhibit Lipopolysaccharide Inducedmap Kinase/Nf-Kb Mediated Severe Sepsis, Mani Maheshwari, Nandini Manne Phd, Shinichi Asano, Eric Blough, Kevin M. Rice, Niraj Nepa,, Erin Fankhanel

Pharmaceutical Science and Research

The life threatening disease of sepsis is associated with high mortality. Septic patient survivability with currently available treatments has failed to improve. The purpose of this study was to evaluate whether lipopolysaccharide (LPS) induced sepsis mortality and associated hepatic dysfunction can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the methods processing of raw data related to our study published in Biomaterials (Selvaraj et al., Biomaterials, 2015, In press) and Data in Brief (Selvaraj et al., Data in Brief, 2015, In Press). The data present here provides confirmation …

Maternal Nicotine Exposure Leads To Impaired Disulfide Bond Formation And Augmented Endoplasmic Reticulum Stress In The Rat Placenta, Michael Wong, Catherine J. Nicholson, Alison C. Holloway, Daniwl Hardy

Physiology and Pharmacology Publications

Maternal nicotine exposure has been associated with many adverse fetal and placental outcomes. Although underlying mechanisms remain elusive, recent studies have identified that augmented endoplasmic reticulum (ER) stress is linked to placental insufficiency. Moreover, ER function depends on proper disulfide bond formation-a partially oxygen-dependent process mediated by protein disulfide isomerase (PDI) and ER oxidoreductases. Given that nicotine compromised placental development in the rat, and placental insufficiency has been associated with poor disulfide bond formation and ER stress, we hypothesized that maternal nicotine exposure leads to both placental ER stress and impaired disulfide bond formation. To test this hypothesis, female Wistar …

Dendritic Distributions Of LH Channels In Experimentally-Derived Multi-Compartment Models Of Oriens-Lacunosum/Moleculare (O-Lm) Hippocampal Interneurons, Vladislav Sekulic, Tse-Chiang Chen, J. Josh Lawrence, Frances K. Skinner

Biomedical and Pharmaceutical Sciences Faculty Publications

The O-LM cell type mediates feedback inhibition onto hippocampal pyramidal cells and gates information flow in the CA1. Its functions depend on the presence of voltage-gated channels (VGCs), which affect its integrative properties and response to synaptic input. Given the challenges associated with determining densities and distributions of VGCs on interneuron dendrites, we take advantage of computational modeling to consider different possibilities. In this work, we focus on hyperpolarization-activated channels (h-channels) in O-LM cells. While h-channels are known to be present in O-LM cells, it is unknown whether they are present on their dendrites. In previous work, we used ensemble …