Medicine and Health Sciences Commons^™

Cocaine Hydrolase-Fc Fusion Proteins For Cocaine And Methods For Utilizing The Same, Chang-Guo Zhan, Fang Zheng, Hsin-Hsiung Tai, Xiabin Chen, Liu Xue, Shurong Hou

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter includes isolated polypeptides that comprise a butyrylcholinestrase (BChE) polypeptide and a second polypeptide. The BChE polypeptide as well as the second polypeptide can be variants and/or fragments thereof. The presently-disclosed subject matter also includes a pharmaceutical composition that comprises the present isolated polypeptide and a suitable pharmaceutical carrier. Further still, methods are provided for treating cocaine-induced conditions, and comprise administering the isolated polypeptide and/or pharmaceutical compositions thereof to an individual.

Multilocular Radiolucency Of The Mandibular Ramus And Body, Galal Omami

Oral Health Practice Faculty Publications

No abstract provided.

From Twisting To Settling Down As A Nurse In China: A Qualitative Study Of The Commitment To Nursing As A Career, Jiao Ye, Aimei Mao, Jialin Wang, Chizimuzo T. C. Okoli, Yuan Zhang, Huiqiong Shuai, Min Lin, Bo Chen, Linli Zhuang

Nursing Faculty Publications

Background

The nurse workforce shortage, partially caused by high work turnover, is an important factor influencing the quality of patient care. Because previous studies concerning Chinese nurse work turnover were predominantly quantitative, they lacked insight into the challenges faced by nurses as they transition from university to their career. A successful transition can result in new nurses’ commitment to the career. As such, this study sought to understand how new nurses commit to the career, and focused on identifying facilitators and barriers to such commitment.

Methods

This was a qualitative study using a grounded theory design. Through purposive sampling, clinical …

Atom Identifiers Generated By A Neighborhood-Specific Graph Coloring Method Enable Compound Harmonization Across Metabolic Databases, Huan Jin, Joshua M. Mitchell, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Metabolic flux analysis requires both a reliable metabolic model and reliable metabolic profiles in characterizing metabolic reprogramming. Advances in analytic methodologies enable production of high-quality metabolomics datasets capturing isotopic flux. However, useful metabolic models can be difficult to derive due to the lack of relatively complete atom-resolved metabolic networks for a variety of organisms, including human. Here, we developed a neighborhood-specific graph coloring method that creates unique identifiers for each atom in a compound facilitating construction of an atom-resolved metabolic network. What is more, this method is guaranteed to generate the same identifier for symmetric atoms, enabling automatic identification of …

Efficient Cocaine Degradation By Cocaine Esterase-Loaded Red Blood Cells, Luigia Rossi, Francesca Pierigè, Marco Agostini, Noemi Bigini, Veronica Termopoli, Yingting Cai, Fang Zheng, Chang-Guo Zhan, Donald W. Landry, Mauro Magnani

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Recombinant bacterial cocaine esterase (CocE) represents a potential protein therapeutic for cocaine use disorder treatment. Unfortunately, the native enzyme was highly unstable and the corresponding mutagenized derivatives, RBP-8000 and E196-301, although improving in vitro thermo-stability and in vivo half-life, were a partial solution to the problem. For cocaine use disorder treatment, an efficient cocaine-metabolizing enzyme with a longer residence time in circulation would be needed. We investigated in vitro the possibility of developing red blood cells (RBCs) loaded with RBP-8000 and E196-301 as a biocompatible system to metabolize cocaine for a longer period of time. RBP 8000 stability within human …

Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu

Pharmaceutical Sciences Faculty Publications

Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl 4-hydroxylase …

Recovery From Covid-19 And Acute Respiratory Distress Syndrome: The Potential Role Of An Intensive Care Unit Recovery Clinic: A Case Report, Kirby P. Mayer, Jamie L. Sturgill, Anna G. Kalema, Melissa K. Soper, Sherif M. Seif, Evan P. Cassity, Jimmi Hatton Kolpek, Esther E. Dupont-Versteegden, Ashley A. Montgomery-Yates, Peter E. Morris

Physical Therapy Faculty Publications

Background

In this case report, we describe the trajectory of recovery of a young, healthy patient diagnosed with coronavirus disease 2019 who developed acute respiratory distress syndrome. The purpose of this case report is to highlight the potential role of intensive care unit recovery or follow-up clinics for patients surviving acute hospitalization for coronavirus disease 2019.

Case Presentation

Our patient was a 27-year-old Caucasian woman with a past medical history of asthma transferred from a community hospital to our medical intensive care unit for acute hypoxic respiratory failure due to bilateral pneumonia requiring mechanical ventilation (ratio of arterial oxygen partial …

Upregulation Of Cpt1a Is Essential For The Tumor-Promoting Effect Of Adipocytes In Colon Cancer, Xiaopeng Xiong, Yang-An Wen, Rachelle Fairchild, Yekaterina Y. Zaytseva, Heidi L. Weiss, B. Mark Evers, Tianyan Gao

Markey Cancer Center Faculty Publications

Colon tumors grow in an adipose tissue-enriched microenvironment. Locally advanced colon cancers often invade into surrounding adipose tissue with a direct contact with adipocytes. We have previously shown that adipocytes promote tumor growth by modulating cellular metabolism. Here we demonstrate that carnitine palmitoyltransferase I (CPT1A), a key enzyme controlling fatty acid oxidation (FAO), was upregulated in colon cancer cells upon exposure to adipocytes or fatty acids. In addition, CPT1A expression was increased in invasive tumor cells within the adipose tissue compared to tumors without direct contact with adipocytes. Silencing CPT1A abolished the protective effect provided by fatty acids against nutrient …

Preterm Birth Prevention In Appalachian Kentucky: Understanding Barriers And Facilitators Related To Transvaginal Ultrasound Cervical Length Surveillance Among Prenatal Care Providers, Anna Hansen, Mairead E. Moloney, Cynthia Cockerham-Morris, Jing Li, Niraj R. Chavan

Sociology Faculty Publications

Background: Appalachian Kentucky has higher-than-average rates of preterm birth (PTB)—a health disparity associated with increased maternal and fetal/neonatal morbidity and neonatal mortality. Transvaginal ultrasound (TVU) cervical length measurement is the best predictor of PTB risk, but is underutilized in Appalachia. This study explores prenatal care providers' TVU-related knowledge and practices, and identifies barriers and facilitators, which impact the adoption of this evidence-based technology.

Materials and Methods: This study recruited providers from three Appalachian Kentucky health care sites. Prenatal care providers took part in semistructured interviews and completed brief survey scales. Questions focused on PTB knowledge, TVU-related barriers, and suggestions for …

Suspected Malignant Hyperthermia And The Application Of A Multidisciplinary Response, Laura Ebbitt, Eric Johnson, Brooke Herndon, Kristina Karrick, Aric Johnson

Pharmacy Practice and Science Faculty Publications

Purpose: Malignant hyperthermia (MH) is a critical and potentially life-threatening emergency associated with inhaled anesthetic and depolarizing neuromuscular blocker administration. This is a single center’s response to MH. Summary: When signs of MH are observed, a page for “anesthesia STAT-MH crisis” is called, triggering a multidisciplinary response, including the deployment of a Malignant Hyperthermia Cart. The MH cart and the delegation of duties allows nurses, physicians and pharmacists to quickly understand their role in the stabilization, transition and recovery of a suspected MH patient. Conclusion: This case highlights the importance of multi-disciplinary involvement in these rare, but potentially fatal, cases.

Encoding The Odor Of Cigarette Smoke, Timothy S. Mcclintock, Naazneen Khan, Yelena Alimova, Madeline Aulisio, Dong Y. Han, Patrick Breheny

Physiology Faculty Publications

The encoding of odors is believed to begin as a combinatorial code consisting of distinct patterns of responses from odorant receptors (ORs), trace-amine associated receptors (TAARs), or both. To determine how specific response patterns arise requires detecting patterns in vivo and understanding how the components of an odor, which are nearly always mixtures of odorants, give rise to parts of the pattern. Cigarette smoke, a common and clinically relevant odor consisting of > 400 odorants, evokes responses from 144 ORs and 3 TAARs in freely behaving male and female mice, the first example of in vivo responses of both ORs and …

Multicentric Synchronous Giant Cell Granulomas Of The Mandible, Galal Omami

Oral Health Practice Faculty Publications

No abstract provided.

Everything Is Science: A Free City-Wide Science Festival, Jarrod W. Creameans, Michelle G. Pitts, Olivia White, Kellen M. Greenwell, Kristie Colón, Sylvie Garneau-Tsodikova, Vincent J. Venditto

Pharmaceutical Sciences Faculty Publications

A week-long, city-wide science festival called Everything is Science (EiS) was developed to educate the community in an informal manner. The festival serves as a platform for presenters from diverse professions to give engaging talks (without PowerPoint slides) to the public, free of charge, in restaurants and bars around town. Over 350 people attended the events over 5 days with 33 presenters. Surveys completed by attendees and session coordinators indicate strong support for this festival. Altogether, the EiS festival serves as a no-cost method to engage with the community and improve science literacy with potential for adoption in other cities.

Mitochondrial Oxidative And Nitrosative Stress And Alzheimer Disease, D. Allan Butterfield, Debra Boyd-Kimball

Chemistry Faculty Publications

Oxidative and nitrosative stress are widely recognized as critical factors in the pathogenesis and progression of Alzheimer disease (AD) and its earlier stage, amnestic mild cognitive impairment (MCI). A major source of free radicals that lead to oxidative and nitrosative damage is mitochondria. This review paper discusses oxidative and nitrosative stress and markers thereof in the brain, along with redox proteomics, which are techniques that have been pioneered in the Butterfield laboratory. Selected biological alterations in—and oxidative and nitrosative modifications of—mitochondria in AD and MCI and systems of relevance thereof also are presented. The review article concludes with a section …

Aluminum Reproductive Toxicity: A Summary And Interpretation Of Scientific Reports, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Publications addressing aluminum (Al)-induced reproductive toxicity were reviewed. Key details were compiled in summary tables. Approximate systemic Al exposure, a measure of bioavailability, was calculated for each exposure, based on the Al percentage in the dosed Al species, Al bioavailability, and absorption time course reports for the exposure route. This was limited to laboratory animal studies because no controlled-exposure human studies were found. Intended Al exposure was compared to unintended dietary Al exposure. The considerable and variable Al content of laboratory animal diets creates uncertainty about reproductive function in the absence of Al. Aluminum-induced reproductive toxicity in female mice and …

Methods For Using Nhanes For Exposure Estimates, Heather R. Campbell, Robert A. Lodder

Pharmaceutical Sciences Faculty Publications

The National Health and Nutrition Examination Survey (NHANES) is a scheme of studies with the objective of measuring the health and nutritional status of adults and children in the United States. The survey is unique in that it has a clinical component (NCT00005154), and combines interviews and physical examinations into its data sets. NHANES is an important program of the National Center for Health Statistics (NCHS). NCHS is a unit of the Centers for Disease Control and Prevention (CDC) and has the responsibility for producing vital and health statistics for the United States. Data from the NHANES studies …

Afatinib For The Treatment Of Egfr Mutation-Positive Nsclc: A Review Of Clinical Findings, R. Donald Harvey, Val R. Adams, Tyler Beardslee, Patrick Medina

Pharmacy Practice and Science Faculty Publications

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors represent the standard of care in patients with EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC). The availability of several EGFR tyrosine kinase inhibitors approved for use in the first-line or later settings in NSCLC warrants an in-depth understanding of the pharmacological properties of, and clinical data supporting, these agents. The second-generation, irreversible ErbB-family blocker, afatinib, has been extensively studied in the context of EGFRm+ NSCLC. Results from the LUX-Lung 3 and 6 studies showed that afatinib was more active and better tolerated than chemotherapy in patients with tumors …

Intrarenal Renin Angiotensin System Imbalance During Postnatal Life Is Associated With Increased Microvascular Density In The Mature Kidney, Carolina Dalmasso, Alejandro R. Chade, Mariela Mendez, Jorge F. Giani, Gregory J. Bix, Kuey Chu Chen, Analia S. Loria

Pharmacology and Nutritional Sciences Faculty Publications

Environmental stress during early life is an important factor that affects the postnatal renal development. We have previously shown that male rats exposed to maternal separation (MatSep), a model of early life stress, are normotensive but display a sex-specific reduced renal function and exacerbated angiotensin II (AngII)-mediated vascular responses as adults. Since optimal AngII levels during postnatal life are required for normal maturation of the kidney, this study was designed to investigate both short- and long-term effect of MatSep on (1) the renal vascular architecture and function, (2) the intrarenal renin-angiotensin system (RAS) components status, and (3) the genome-wide expression …

A Smartphone-Based Support Group For Alcoholism: Effects Of Giving And Receiving Emotional Support On Coping Self-Efficacy And Risky Drinking, Woohyun Yoo, Dhavan V. Shah, Ming-Yuan Chih, David H. Gustafson

Health and Clinical Sciences Faculty Publications

The purpose of this study was to investigate the nature and effects of exchanging emotional support via a smartphone-based support group for patients with alcohol dependence. Of the 349 patients who met the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for alcohol dependence, 153 patients participated in the discussion group within the Addiction-Comprehensive Health Enhancement Support System, a smartphone application aimed at reducing relapse. This was developed to prevent problem drinking by offering individuals in recovery for alcohol dependence automated 24/7 recovery support services and frequent assessment of their symptom status as part of their addiction care. …

Implementation Evaluation Of A Professional Development Program For Comprehensive School Physical Activity Leaders, Russell L. Carson, Ann Pulling Kuhn, Justin B. Moore, Darla M. Castelli, Aaron Beighle, Katie L. Hodgin, Brian Dauenhauer

Kinesiology and Health Promotion Faculty Publications

The purpose of this study was to conduct an implementation monitoring evaluation of a yearlong comprehensive school physical activity program (CSPAP) professional development program across eight multi-state physical education (PE) teacher cohorts. Mixed-method data were collected during a three-year implementation period via workshop attendance sheets and evaluations, post-workshop implementation plans and artifacts, and follow-up phone interviews to enumerate and evaluate the program’s process of recruitment, reach, dose delivered, dose received, fidelity, and context. Recruitment strategies reached a total of 234 PE teacher attendees across eight workshops, with 77 PE teachers (primarily female, elementary, public school teachers) completing all program requirements. …

E-Cigarette Availability, Price Promotions And Marketing At The Point-Of Sale In The Contiguous United States (2014-2015): National Estimates And Multilevel Correlates, Heather D'Angelo, Shyanika W. Rose, Shelley D. Golden, Tara Queen, Kurt M. Ribisl

Behavioral Science Faculty Publications

Electronic cigarette (e-cigarette) sales and use have increased rapidly, yet point-of-sale e-cigarette availability and marketing is understudied. We estimated changes in e-cigarette availability and marketing among tobacco retailers in the U.S., and associations with neighborhood characteristics. A national sample of tobacco retailers in the Contiguous U.S. was audited in 2014 and 2015 (n = 1,905 and n = 2,126, respectively) to observe e-cigarette availability and marketing (signs, ads, displays and promotions) and generate national prevalence estimates. Store, neighborhood and state level correlates of 2015 e-cigarette availability, price promotions and exterior advertising were analyzed using multilevel mixed-effects generalized linear models. E-cigarettes …

Risk Factors For And Prediction Of Post-Intubation Hypotension In Critically Ill Adults: A Multicenter Prospective Cohort Study, Nathan J. Smischney, Rahul Kashyap, Ashish K. Khanna, Ernesto Brauer, Lee E. Morrow, Mohamed O. Seisa, Darrell R. Schroeder, Daniel A. Diedrich, Ashley Montgomery, Pablo Moreno Franco, Uchenna R. Ofoma, David A. Kaufman, Ayan Sen, Cynthia Callahan, Chakradhar Venkata, Gozde Demiralp, Rudy Tedja, Sarah Lee, Mariya Geube, Santhi I. Kumar, Peter E. Morris, Vikas Bansal, Salim Surani, On Behalf Of Sccm Discovery (Critical Care Research Network Of Critical Care Medicine) Hemair Investigators Consortium

Internal Medicine Faculty Publications

OBJECTIVE: Hypotension following endotracheal intubation in the ICU is associated with poor outcomes. There is no formal prediction tool to help estimate the onset of this hemodynamic compromise. Our objective was to derive and validate a prediction model for immediate hypotension following endotracheal intubation.

METHODS: A multicenter, prospective, cohort study enrolling 934 adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 was conducted to derive and validate a prediction model for immediate hypotension following endotracheal intubation. We defined hypotension as: 1) mean arterial pressure < 65 mmHg; 2) systolic blood pressure < 80 mmHg and/or decrease in systolic blood pressure of 40% from baseline; 3) or the initiation or increase in any vasopressor in the 30 minutes following endotracheal intubation.

RESULTS: Post-intubation hypotension developed in 344 (36.8%) patients. …

Hypusination Of Eif5a Regulates Cytoplasmic Tdp-43 Aggregation And Accumulation In A Stress-Induced Cellular Model, Shayna Smeltzer, Zainuddin Quadri, Abraian Miller, Frank Zamudio, Jordan Hunter, Nicholas J.F. Stewart, Sheba Saji, Daniel C. Lee, Dale Chaput, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

TAR DNA-binding protein 43 (TDP-43) is a nuclear RNA/DNA binding protein involved in mRNA metabolism. Aberrant mislocalization to the cytoplasm and formation of phosphorylated/aggregated TDP-43 inclusions remains the hallmark pathology in a spectrum of neurodegenerative diseases, including frontotemporal disorders and Alzheimer's disease. Eukaryotic Translation Initiation Factor 5A undergoes a unique post-translation modification of lysine to hypusine (K50), which determines eIF5A binding partners. We used a sodium arsenite-induced cellular stress model to investigate the role of hypusinated eIF5A (eIF5A^HypK50) in governing TDP-43 cytoplasmic mislocalization and accumulation in stress granule. Our proteomics and functional data provide evidence that eIF5A interacts …

Cardiorespiratory Fitness Diminishes The Effects Of Age On White Matter Hyperintensity Volume, Nathan F. Johnson, Ahmed A. Bahrani, David K. Powell, Gregory A. Jicha, Brian T. Gold

Physical Therapy Faculty Publications

White matter hyperintensities (WMHs) are among the most commonly observed marker of cerebrovascular disease. Age is a key risk factor for WMH development. Cardiorespiratory fitness (CRF) is associated with increased vessel compliance, but it remains unknown if high CRF affects WMH volume. This study explored the effects of CRF on WMH volume in community-dwelling older adults. We further tested the possibility of an interaction between CRF and age on WMH volume. Participants were 76 adults between the ages of 59 and 77 (mean age = 65.36 years, SD = 3.92) who underwent a maximal graded exercise test and structural brain …

Corticospinal Activity During A Single-Leg Stance In People With Chronic Ankle Instability, Masafumi Terada, Kyle B. Kosik, Ryan S. Mccann, Colin Drinkard, Phillip A. Gribble

Athletic Training and Clinical Nutrition Faculty Publications

PURPOSE: The aim of the study was to determine whether corticospinal excitability and inhibition of the tibialis anterior during single-leg standing differs among individuals with chronic ankle instability (CAI), lateral ankle sprain copers, and healthy controls.

METHODS: Twenty-three participants with CAI, 23 lateral ankle sprain copers, and 24 healthy control participants volunteered. Active motor threshold (AMT), normalized motor-evoked potential (MEP), and cortical silent period (CSP) were evaluated by transcranial magnetic stimulation while participants performed a single-leg standing task.

RESULTS: Participants with CAI had significantly longer CSP at 100% of AMT and lower normalized MEP at 120% of AMT compared to …

Igf-1r Inhibition Induces Mek Phosphorylation To Promote Survival In Colon Carcinomas, Qing Wang, Yan Zhang, Jiang Zhu, Honggang Zheng, Shuntai Chen, Li Chen, Hsin-Sheng Yang

Toxicology and Cancer Biology Faculty Publications

The insulin-like growth factor 1 receptor (IGF-1R) governs several signaling pathways for cell proliferation, survival, and anti-apoptosis. Thus, targeting IGF-1R appears as a reasonable rationale for tumor treatment. However, clinical studies showed that inhibition of IGF-1R has very limited efficacy due to the development of resistance to IGF-1R blockade in tumor cells. Here, we discovered that prolonged treatment of colon cancer cells with IGF-1R inhibitors (BMS-754807 and GSK1838705A) stimulates p70 KDa ribosomal protein S6 kinase 1 (p70S6K1) activation, a well-known kinase signaling for cell survival. We also found that p70S6K1 activation by IGF-1R inhibition is independent of K-Ras and PIK3CA …

Feasibility Of Dual-Task Gait To Estimate Alzheimer's Related Cognitive Decline In Down Syndrome, Kathryn L. Van Pelt, Lisa Mason Koehl, Allison M. Caban-Holt, Amelia J. Anderson-Mooney, Elizabeth Head, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

Introduction: The striatum and frontal lobes have been shown to have early Alzheimer's disease (AD) neuropathology and are critical for motor and cognitive function. We hypothesized gait would be associated with early-stage dementia in Down syndrome (DS), a cohort at risk for AD.

Methods: Twenty-eight participants with DS were enrolled in the study. Participants walked at their self-selected pace and while completing a dual task (counting, obstacle, or counting+obstacle).

Results: All participants were able to complete the self-paced condition and 78.57-96.42% completed the dual-task conditions. There was a trend for greater dual-task effects on gait velocity based on dementia diagnosis. …

Limbic-Predominant Age-Related Tdp-43 Encephalopathy Differs From Frontotemporal Lobar Degeneration, John L. Robinson, Sílvia Porta, Filip G. Garrett, Panpan Zhang, Sharon X. Xie, Eunran Suh, Vivianna M. Van Deerlin, Erin L. Abner, Gregory A. Jicha, Justin M. Barber, Virginia M-Y Lee, Edward B. Lee, John Q. Trojanowski, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

TAR-DNA binding protein-43 (TDP-43) proteinopathy is seen in multiple brain diseases. A standardized terminology was recommended recently for common age-related TDP-43 proteinopathy: limbic-predominant, age-related TDP-43 encephalopathy (LATE) and the underlying neuropathological changes, LATE-NC. LATE-NC may be co-morbid with Alzheimer’s disease neuropathological changes (ADNC). However, there currently are ill-defined diagnostic classification issues among LATE-NC, ADNC, and frontotemporal lobar degeneration with TDP-43 (FTLD-TDP). A practical challenge is that different autopsy cohorts are composed of disparate groups of research volunteers: hospital- and clinic-based cohorts are enriched for FTLD-TDP cases, whereas community-based cohorts have more LATE-NC cases. Neuropathological methods also differ across laboratories. Here, …

Effect Of Niacin Monotherapy On High Density Lipoprotein Composition And Function, Scott M. Gordon, Marcelo J. Amar, Kianoush Jeiran, Michael Stagliano, Emma Staller, Martin P. Playford, Nehal N. Mehta, Tomas Vaisar, Alan T. Remaley

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Niacin has modest but overall favorable effects on plasma lipids by increasing high density lipoprotein cholesterol (HDL-C) and lowering triglycerides. Clinical trials, however, evaluating niacin therapy for prevention of cardiovascular outcomes have returned mixed results. Recent evidence suggests that the HDL proteome may be a better indicator of HDL's cardioprotective function than HDL-C. The objective of this study was to evaluate the effect of niacin monotherapy on HDL protein composition and function.

METHODS: A 20-week investigational study was performed with 11 participants receiving extended-release niacin (target dose = 2 g/day) for 16-weeks followed by a 4-week washout period. HDL …

The Bach1/Nrf2 Axis In Brain In Down Syndrome And Transition To Alzheimer Disease-Like Neuropathology And Dementia, Marzia Perluigi, Antonella Tramutola, Sara Pagnotta, Eugenio Barone, D. Allan Butterfield

Chemistry Faculty Publications

Down syndrome (DS) is the most common genetic cause of intellectual disability that is associated with an increased risk to develop early-onset Alzheimer-like dementia (AD). The brain neuropathological features include alteration of redox homeostasis, mitochondrial deficits, inflammation, accumulation of both amyloid beta-peptide oligomers and senile plaques, as well as aggregated hyperphosphorylated tau protein-containing neurofibrillary tangles, among others. It is worth mentioning that some of the triplicated genes encoded are likely to cause increased oxidative stress (OS) conditions that are also associated with reduced cellular responses. Published studies from our laboratories propose that increased oxidative damage occurs early in life in …