Biochemistry, Biophysics, and Structural Biology Commons^™

Potential Use Of Biotherapeutic Bacteria To Target Colorectal Cancer-Associated Taxa, Gareth Lawrence, Maire Begley, Paul D. Cotter, Caitríona M. Guinane

Department of Biological Sciences Publications

The role of the gut microbiome in human health and disease is the focus of much attention. It has been widely agreed upon that our gut bacteria play a role in host immunity, nutrient absorption, digestion, metabolism, and other key drivers of health. Furthermore, certain microbial signatures and specific taxa have also been associated with the development of diseases, such as obesity; inflammatory bowel disease; and, indeed, colorectal cancer (CRC), which is the focus of this review. By extension, such taxa represent potential therapeutic targets. In particular, the emerging human pathogen Fusobacterium nucleatum represents an important agent in CRC development …

Trka Undergoes A Tetramer-To-Dimer Conversion To Open Trkh Which Enables Changes In Membrane Potential, Hanzhi Zhang, Yaping Pan, Liya Hu, M Ashley Hudson, Katrina S Hofstetter, Zhichun Xu, Mingqiang Rong, Zhao Wang, B V Venkataram Prasad, Steve W Lockless, Wah Chiu, Ming Zhou

Faculty, Staff and Students Publications

TrkH is a bacterial ion channel implicated in K+ uptake and pH regulation. TrkH assembles with its regulatory protein, TrkA, which closes the channel when bound to ADP and opens it when bound to ATP. However, it is unknown how nucleotides control the gating of TrkH through TrkA. Here we report the structures of the TrkH-TrkA complex in the presence of ADP or ATP. TrkA forms a tetrameric ring when bound to ADP and constrains TrkH to a closed conformation. The TrkA ring splits into two TrkA dimers in the presence of ATP and releases the constraints on TrkH, resulting …

The Mitochondrial Hsp90 Paralog Trap1 Forms An Oxphos-Regulated Tetramer And Is Involved In Mitochondrial Metabolic Homeostasis, Abhinav Joshi, Li Dai, Yanxin Liu, Jungsoon Lee, Nastaran Mohammadi Ghahhari, Gregory Segala, Kristin Beebe, Lisa M Jenkins, Gaelyn C Lyons, Lilia Bernasconi, Francis T F Tsai, David A Agard, Len Neckers, Didier Picard

Faculty, Staff and Students Publications

BACKGROUND: The molecular chaperone TRAP1, the mitochondrial isoform of cytosolic HSP90, remains poorly understood with respect to its pivotal role in the regulation of mitochondrial metabolism. Most studies have found it to be an inhibitor of mitochondrial oxidative phosphorylation (OXPHOS) and an inducer of the Warburg phenotype of cancer cells. However, others have reported the opposite, and there is no consensus on the relevant TRAP1 interactors. This calls for a more comprehensive analysis of the TRAP1 interactome and of how TRAP1 and mitochondrial metabolism mutually affect each other.

RESULTS: We show that the disruption of the gene for TRAP1 in …

Rhoa-Rock Signaling As A Therapeutic Target In Traumatic Brain Injury, Shalaka Mulherkar, Kimberley F Tolias

Faculty, Staff and Students Publications

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. TBIs, which range in severity from mild to severe, occur when a traumatic event, such as a fall, a traffic accident, or a blow, causes the brain to move rapidly within the skull, resulting in damage. Long-term consequences of TBI can include motor and cognitive deficits and emotional disturbances that result in a reduced quality of life and work productivity. Recovery from TBI can be challenging due to a lack of effective treatment options for repairing TBI-induced neural damage and alleviating functional impairments. Central nervous system (CNS) …

Development And Characterization Of A Wee1 Kinase Degrader, Zhengnian Li, Benika J Pinch, Calla M Olson, Katherine A Donovan, Radosław P Nowak, Caitlin E Mills, David A Scott, Zainab M Doctor, Nicholas A Eleuteri, Mirra Chung, Peter K Sorger, Eric S Fischer, Nathanael S Gray

Faculty, Staff and Students Publications

The G1/S cell cycle checkpoint is frequently dysregulated in cancer, leaving cancer cells reliant on a functional G2/M checkpoint to prevent excessive DNA damage. Wee1 regulates the G2/M checkpoint by phosphorylating CDK1 at Tyr15 to prevent mitotic entry. Previous drug development efforts targeting Wee1 resulted in the clinical-grade inhibitor, AZD1775. However, AZD1775 is burdened by dose-limiting adverse events, and has off-target PLK1 activity. In an attempt to overcome these limitations, we developed Wee1 degraders by conjugating AZD1775 to the cereblon (CRBN)-binding ligand, pomalidomide. The resulting lead compound, ZNL-02-096, degrades Wee1 while sparing PLK1, induces G2/M accumulation at 10-fold lower doses …

First Records Of Established Populations Of Ixodes Scapularis (Acari: Ixodidae) Collected From Three Nebraska Counties, Lindsey E. Nielsen, Roberto Cortinas, Paul D. Fey, Peter C. Iwen, David H. Nielsen

School of Veterinary and Biomedical Sciences: Faculty Publications

Reported cases of Lyme disease in Nebraska have been assumed to be imported from other endemic areas. Previous surveillance efforts provided no evidence of established populations as only individual specimens of Ixodes scapularis (Say) had been collected. In the winter of 2018, adult I. scapularis were found on a dog at Two Rivers State Recreation Area, Douglas County, prompting tick collection at the site and nearby natural areas. In May 2019, all life stages of host-seeking I. scapularis were collected using dragging and flagging techniques in sites located near the Platte River in Douglas, Sarpy, and Saunders counties. This is …

Intimate Attachment Of Escherichia Coli O157:H7 To Urinary Bladder Epithelium In The Gnotobiotic Piglet Model, Rodney A. Moxley, Tom W. Bargar, Stephen D. Kachman, Diane R. Baker, David H. Francis

School of Veterinary and Biomedical Sciences: Faculty Publications

Enterohemorrhagic Escherichia coli (EHEC), a pathogenic subset of Shiga toxin-producing E. coli (STEC), is an important cause of hemorrhagic colitis and hemolytic–uremic syndrome (HUS), and a rare cause of urinary tract infections (UTIs) with associated HUS. EHEC strains attach intimately to intestinal epithelium with formation of actin pedestals (attaching-effacing (A/E) lesions); however, the mechanism of EHEC attachment to the uroepithelium is unknown. We conducted a retrospective study on archived urinary bladder specimens from gnotobiotic piglets that naturally developed cystitis associated with EHEC O157:H7 infection following oral inoculation and fecal shedding. Paraffin-embedded bladder tissues from three piglets with cystitis and immunohistochemical …

Triggers Of Inflammatory Heart Disease, Ninaad Lasrado, Bharathi Yalaka, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Inflammatory heart disease (IHD) is a group of diseases that includes pericarditis, myocarditis, and endocarditis. Although males appear to be more commonly affected than females, IHD can be seen in any age group. While the disease can be self-limiting leading to full recovery, affected individuals can develop chronic disease, suggesting that identification of primary triggers is critical for successful therapies. Adding to this complexity, however, is the fact that IHD can be triggered by a variety of infectious and non-infectious causes that can also occur as secondary events to primary insults. In this review, we discuss the immunological insights into …

Current Status Of Zika Virus Vaccines: Successes And Challenges, Aryamav Pattnaik, Bikash R. Sahoo, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

The recently emerged Zika virus (ZIKV) spread to the Americas, causing a spectrum of congenital diseases including microcephaly in newborn and Guillain-Barré syndrome (GBS) in adults. The unprecedented nature of the epidemic and serious diseases associated with the viral infections prompted the global research community to understand the immunopathogenic mechanisms of the virus and rapidly develop safe and efficacious vaccines. This has led to a number of ZIKV vaccine candidates that have shown significant promise in human clinical trials. These candidates include nucleic acid vaccines, inactivated vaccines, viral-vectored vaccines, and attenuated vaccines. Additionally, a number of vaccine candidates have been …

Rapid Differentiation Of Moraxella Bovoculi Genotypes 1 And 2 Using Maldi-Tof Mass Spectrometry Profiles, Matthew M. Hille, Aaron M. Dickey, Kara Robbins, Michael L. Clawson, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Moraxella bovoculi is the most frequently isolated bacteria from the eyes of cattle with Infectious Bovine Keratoconjunctivitis (IBK), also known as bovine pinkeye. Two distinct genotypes of M. bovoculi, genotype 1 and genotype 2, were characterized after whole genome sequencing showed a large degree of single nucleotide polymorphism (SNP) diversity within the species. To date, both genotypes have been isolated from the eyes of cattle without clinical signs of IBK while only genotype 1 strains have been isolated from the eyes of cattle with clinical signs of IBK. We used 38 known genotype 1 strains and 26 known genotype …

Genomic-Based Identification Of Environmental And Clinical Listeria Monocytogenes Strains Associated With An Abortion Outbreak In Beef Heifers, Katherine J. Whitman, James L. Bono, Michael L. Clawson, John D. Loy, Joseph M. Bosilevac, Terrance M. Arthur, Jeff D. Ondrak

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: In a beef cattle facility an outbreak of abortions occurred over a 36-day period and included samples from two aborted (non-viable) fetuses and 21 post-abortion clinical cases. There are numerous etiologies, including clinical listeriosis. At the species level, Listeria monocytogenes is ubiquitous in cattle production environments, including soil, feed, and occasionally water sources, and is a common enteric resident of cattle and other mammals. There are four genetically distinct lineages of L. monocytogenes (I-IV), with most lineage III and IV isolates obtained from ruminants. Definitive diagnosis of L. monocytogenes as a causative agent in disease outbreaks relies upon case …

Molecular And Functional Characterization Of Α-Galactosyl Epitopes In Trypanosoma Cruzi, Uriel Ortega Rodriguez

Open Access Theses & Dissertations

Trypanosoma cruzi, the causative agent of Chagas disease (CD) currently affects 6-7 million people across the world. Currently, only two drugs, benznidazole and nifurtimox, are available for treatment of CD and they are highly toxic and less effective in the chronic stage of the disease. Specific biomarkers for diagnosis and follow-up of treatment do not exist in the clinical settings. following chemotherapy, patients take approximately 10-20 years to exhibit negative seroconversion with the conventional serology assays. Moreover, there is no vaccine available to prevent or treat CD. T. cruzi contains a complex cell surface consisting of several classes of glycoconjugates …

Pneumovirus Infections: Understanding Rsv And Hmpv Entry, Replication, And Spread, Jonathan T. Kinder

Theses and Dissertations--Molecular and Cellular Biochemistry

Pneumoviruses including human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are significant causes of respiratory tract infections globally. Children, elderly, and immunocompromised patients are at the greatest risk for developing severe infections, which can have devastating outcomes. Although these viruses are ubiquitous with significant impacts on human health, there are no antivirals or vaccines available. The only FDA approved therapy is a monoclonal antibody for RSV, given prophylactically during the infectious season, and this treatment is only available for high risk infants. The work presented in this thesis aims to increase our understanding of how these viruses enter, replicate, and …

Uterine Torsion Dystocia Complicated By Perosomus Elumbis In An Angus Calf Associated With A Consanguineous Mating, Alyssa B. Helms, Riley E. Thompson, Sam Lawton, Jessica L. Petersen, Allison Watson, Mee-Ja Sula, David J. Steffen, Brian K. Whitlock

School of Veterinary and Biomedical Sciences: Faculty Publications

A six-year-old multiparous Angus cow was presented for dystocia. Vaginal and rectal examinations revealed an approximately 360° counterclockwise uterine torsion. The torsion was corrected by rolling the cow counterclockwise (three episodes) with the aid of a plank coupled with manual detorsion via the vagina. The placement of obstetric chains followed by manual traction ultimately delivered a stillborn male calf with evidence of vertebral aplasia, arthrogryposis, and abdominal organ herniation. Patient history and subsequent parentage verification revealed that the calf was the result of a consanguineous (mother to son) mating. Tissue samples from the affected calf and blood samples from the …

Identification Of Immunogenic Epitopes That Permit The Detection Of Antigen-Specific T Cell Responses In Multiple Serotypes Of Group B Coxsackievirus Infections, Ninaad Lasrado, Arunakumar Gangaplara, Rajkumar Arumugam, Chandirasegara Massilamany, Sayli Pokal, Yuzhen Zhou, Shi-Hua Xiang, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Coxsackievirus group B (CVB) contains six serotypes that can affect various organs. Some of these organ-specific diseases such as myocarditis and pancreatitis can be caused by more than one serotype. Thus, development of immunological tools common to multiple serotypes is desired. This is especially critical for analyzing antigen-specific T cell responses at a single cell level. To this end, we made efforts to identify the immunogenic epitopes of CVB3 leading us to localize three T cell epitopes within the viral protein 1 (VP1) namely, VP1 681–700, VP1 721–740 and VP1 771–790. First, we confirmed their immunogenicity in the immunization settings. …

First Records Of Established Populations Of Ixodes Scapularis (Acari: Ixodidae) Collected From Three Nebraska Counties, Lindsey E. Nielsen, Roberto Cortinas, Paul D. Fey, Peter C. Iwen, David H. Nielsen

School of Veterinary and Biomedical Sciences: Faculty Publications

Reported cases of Lyme disease in Nebraska have been assumed to be imported from other endemic areas. Previous surveillance efforts provided no evidence of established populations as only individual specimens of Ixodes scapularis (Say) had been collected. In the winter of 2018, adult I. scapularis were found on a dog at Two Rivers State Recreation Area, Douglas County, prompting tick collection at the site and nearby natural areas. In May 2019, all life stages of host-seeking I. scapularis were collected using dragging and flagging techniques in sites located near the Platte River in Douglas, Sarpy, and Saunders counties. This is …

Methods Of Treating Or Preventing Zika Virus Infection, Shi-Hua Xiang, Nicholas Palermo, Asit K. Pattnaik, Aryamay Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

This document relates to methods and materials for treating a mammal having a Zika virus (ZIKV) infection. For example, a composition including one or more non-nucleoside RNA polymerase inhibitors can be administered to a mammal having, or at risk of developing, a ZIKV infection to treat the mammal.

Recent Advances In The Diagnosis Of Classical Swine Fever And Future Perspectives, Lihua Wang, Rachel Madera, Yuzhen Li, D. Scott Mcvey, Jishu Shi

School of Veterinary and Biomedical Sciences: Faculty Publications

Classical swine fever (CSF) is a highly contagious viral disease of pigs, including wild boar. It is regarded as one of the major problems in the pig industry as it is still endemic in many regions of the world and has the potential to cause devastating epidemics, particularly in countries free of the disease. Rapid and reliable diagnosis is of utmost importance in the control of CSF. Since clinical presentations of CSF are highly variable and may be confused with other viral diseases in pigs, laboratory diagnosis is indispensable for an unambiguous diagnosis. On an international level, well-established diagnostic tests …

Evaluation Of A Baculovirus-Expressed Vp2 Subunit Vaccine For The Protection Of White-Tailed Deer (Odocoileus Virginianus) From Epizootic Hemorrhagic Disease, Sun Young Sunwoo, Leela E. Noronha, Igor Morozov, Jessie D. Trujilo, In Joong Kim, Erin E. Schirtzinger, Bonto Faburary, Barbara S. Drolet, Kinga Urbaniak, D. Scott Mcvey, David A. Meekins, Mitchell V. Palmer, Velmurugan Balaraman, William C. Wilson, Juergen A. Richt

School of Veterinary and Biomedical Sciences: Faculty Publications

Epizootic hemorrhagic disease virus (EHDV) is an arthropod-transmitted RNA virus and the causative agent of epizootic hemorrhagic disease (EHD) in wild and domestic ruminants. In North America, white-tailed deer (WTD) experience the highest EHD-related morbidity and mortality, although clinical disease is reported in cattle during severe epizootics. No commercially licensed EHDV vaccine is available in North America. The objective of this study was to develop and evaluate a subunit vaccine candidate to control EHD in WTD. Recombinant VP2 (rVP2) outer capsid proteins of EHDV serotypes 2 (EHDV-2) and 6 (EHDV-6) were produced in a baculovirus-expression system. Mice and cattle vaccinated …

Amphiphilic Cyclobutenes And Cylobutanes, Wantanee Sittiwong, Patrick H. Dussault, Raul G. Barletta, Robert Powers

School of Veterinary and Biomedical Sciences: Faculty Publications

This disclosure relates to amphiphilic compounds containing a cyclobutene or cyclobutane moiety. In some embodiments, the compounds are useful for treating infection by Mycobacterium such as Mycobacterium tuberculosis. Cyclobutene containing compounds are also useful as monomers in the preparation of amphiphilic polymers.

Non-Neuroinvasivevirusesand Uses Thereof, Gregory A. Smith, Patricia J. Sollars, Gary E. Pickard, Ekaterina E. Heldwein

School of Veterinary and Biomedical Sciences: Faculty Publications

Provided herein are compositions and methods for vaccination and research applications. In particular, provided herein are non-neuroinvasive herpesviruses and alpha herpesviruses and uses thereof.

Mitochondrial Metabolism In Astrocytes Regulates Brain Bioenergetics, Neurotransmission And Redox Balance, Jordan Rose, Christian Brian, Aglaia Pappa, Mihalis I. Panayiotidi, Rodrigo Franco

School of Veterinary and Biomedical Sciences: Faculty Publications

In the brain, mitochondrial metabolism has been largely associated with energy production, and its dysfunction is linked to neuronal cell loss. However, the functional role of mitochondria in glial cells has been poorly studied. Recent reports have demonstrated unequivocally that astrocytes do not require mitochondria to meet their bioenergetics demands. Then, the question remaining is, what is the functional role of mitochondria in astrocytes? In this work, we review current evidence demonstrating that mitochondrial central carbon metabolism in astrocytes regulates overall brain bioenergetics, neurotransmitter homeostasis and redox balance. Emphasis is placed in detailing carbon source utilization (glucose and fatty acids), …

Mechanisms Of Sex Hormones In Autoimmunity: Focus On Eae, Ninaad Lasrado, Ting Jia, Chandirasegaran Massilamany, Rodrigo Franco, Zsolt Illes, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Sex-related differences in the occurrence of autoimmune diseases is well documented, with females showing a greater propensity to develop these diseases than their male counterparts. Sex hormones, namely dihydrotestosterone and estrogens, have been shown to ameliorate the severity of inflammatory diseases. Immunologically, the beneficial effects of sex hormones have been ascribed to the suppression of effector lymphocyte responses accompanied by immune deviation from pro-inflammatory to anti-inflammatory cytokine production. In this review, we present our view of the mechanisms of sex hormones that contribute to their ability to suppress autoimmune responses with an emphasis on the pathogenesis of experimental autoimmune encephalomyelitis.

Evidence For Anti-Viral Effects Of Complete Freund’S Adjuvant In The Mouse Model Of Enterovirus Infection, Arunakumar Gangaplara, Chandirasegaran Massilamany, Ninaad Lasrado, David J. Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Group B coxsackieviruses (CVBs) belonging to the genus, Enterovirus and contain six serotypes that induce various diseases, whose occurrence may involve the mediation of more than one serotype. We recently identified immunogenic epitopes within coxsackieviruses B3 (CVB3) viral protein 1 that induce anti-viral T cell responses in mouse models of CVB infections. In our investigations to determine the protective responses of the viral epitopes, we unexpectedly noted that animals immunized with complete Freund’s adjuvant (CFA) alone and later challenged with CVB3 were completely protected against myocarditis. Similarly, the pancreatitis-inducing ability of CVB3 was remarkably reduced to only 10% in the …

Porcine Reproductive And Respiratory Syndrome Virus Reverse Genetics And The Major Applications, Jayeshbhai Chaudhari, Hiep Vu

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive sense, single-stranded RNA virus that is known to infect only pigs. The virus emerged in the late 1980s and became endemic in most swine producing countries, causing substantial economic losses to the swine industry. The first reverse genetics system for PRRSV was reported in 1998. Since then, several infectious cDNA clones for PRRSV have been constructed. The availability of these infectious cDNA clones has facilitated the genetic modifications of the viral genome at precise locations. Common approaches to manipulate the viral genome include site-directed mutagenesis, deletion of viral genes or …

An Evidence For Surface Expression Of An Immunogenic Epitope Of Sarcoplasmic/Endoplasmic Reticulum Calcium-Atpase2a On Antigen-Presenting Cells From Naive Mice In The Mediation Of Autoimmune Myocarditis, Rajkumar Arumugam, Bharathi Yalaka, Chandirasegara Massilamany, Ms Shihabudeen Haider Ali, Ninaad Lasrado, Sabarirajan Jayaraja, Jean-Jack Riethoven, Xinghui Sun, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

We recently reported identification of sarcoplasmic/endoplasmic reticulum calcium-ATPase2a (SERCA2a) 971–990, which induces atrial myocarditis by generating autoreactive T cells in A/J mice. However, it was unknown how antigen-sensitized T cells could recognize SERCA2a 971–990, since SERCA2a-expression is confined to an intracellular compartment. In this report, we present evidence that antigen-presenting cells (APCs) from lymphoid and non-lymphoid organs in naïve animals present SERCA2a 971–990 and stimulate antigen-specific T cells. Using major histocompatibility complex (MHC) class II dextramers for SERCA2a 971–990, we created a panel of T cell hybridomas and demonstrated that splenocytes from naïve A/J mice stimulated the hybridoma cells without …

Viral Myocarditis Involves The Generation Of Autoreactive T Cells With Multiple Antigen Specificities That Localize In Lymphoid And Non-Lymphoid Organs In The Mouse Model Of Cvb3 Infection, Rakesh H. Basavalingappa, Rajkumar Arumugam, Ninaad Lasrado, Bharathi Yalaka, Chandirasegara Massilamany, Arunakumar Gangaplara, Jean-Jack Riethoven, Shi-Hua Xiang, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Autoreactive T cells may contribute to post-viral myocarditis induced with Coxsackievirus B3 (CVB3), but the underlying mechanisms of their generation are unclear. Here, we have comprehensively analyzed the generation of antigen-specific, autoreactive T cells in the mouse model of CVB3 infection for antigens implicated in patients with myocarditis/dilated cardiomyopathy. First, comparative analysis of CVB3 proteome with five autoantigens led us to identify three mimicry epitopes, one each from adenine nucleotide translocator 1 (ANT), sarcoplasmic/ endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and cardiac troponin I. None of these induced cross-reactive T cell responses. Next, we generated major histocompatibility complex (MHC) class …

Meta-Analysis Comparing Watchmantm And Amplatzer Devices For Stroke Prevention In Atrial Fibrillation, Indranill Basu Ray, Dibbendhu Khanra, Sumit Shah, Sudhanva Char, Xiaoming Jia, Wilson Lam, Nilesh Mathuria, Mehdi Razavi, Bhavna Jain, Dhanunjaya Lakkireddy, Saibal Kar, Andrea Natale, Adedayo Adeboye, John Lynn Jefferies, Sripal Bangalore, Samuel Asirvatham, Mohammad Saeed

Faculty, Staff and Students Publications

Background: For patients with atrial fibrillation who are at high risk for bleeding or who cannot tolerate oral anticoagulation, left atrial appendage (LAA) closure represents an alternative therapy for reducing risk for thromboembolic events.

Objectives: To compare the efficacy and safety of the Amplatzer and Watchman^TM LAA closure devices.

Methods: A meta-analysis was performed of studies comparing the safety and efficacy outcomes of the two devices. The Newcastle-Ottawa Scale was used to appraise study quality.

Results: Six studies encompassing 614 patients were included in the meta-analysis. Overall event rates were low for both devices. No significant differences between the …

Spironolactone In Pulmonary Arterial Hypertension: Results Of A Cross-Over Study, Zeenat Safdar, Adaani Frost, Arya Basant, Anita Deswal, E O'Brian Smith, Mark Entman

Faculty, Staff and Students Publications

The renin–angiotensin–aldosterone system is implicated in the pathophysiology of pulmonary arterial hypertension. We undertook this study to determine the effects of spironolactone, a mineralocorticoid receptor blocker, on collagen metabolism in pulmonary arterial hypertension patients. After obtaining institutional review board approval and informed consent, 42 pulmonary arterial hypertension patients were prospectively enrolled and 35 patients completed the 16-week randomized double-blinded crossover clinical trial. Subjects received 50 mg spironolactone or placebo and at the end of week 8, treatment arm was switched. Circulating levels of collagen biomarkers, brain natriuretic peptide, and aldosterone levels were measured, and six-minute walk distance, liver function tests, …

Pregnancy And Lactation In A 67-Year-Old Elderly Gravida Following Donor Oocyte, Leila Magistrado, Mary C Tolcher, Anju Suhag, Sonal Zambare, Kjersti M Aagaard

Faculty, Staff and Students Publications

There is limited data on the anticipated perinatal course among gravidae in their sixth and seventh decades. Our objective was to describe the relatively uncomplicated prenatal, intrapartum, and postpartum course of a 67-year-old essential primigravida. Briefly, our patient conceived a singleton pregnancy via IVF with donor oocytes, then presented at 13 6/7 weeks of gestation to initiate prenatal care. Her medical history was significant for chronic hypertension, hyperlipidemia, and obesity. Her cardiac function was monitored throughout pregnancy, and she delivered at 36 1/7 weeks by cesarean for a decline in left ventricular function with mitral regurgitation. Her intrapartum and postpartum …