Medicine and Health Sciences Commons^™

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 …

Thermophilic Phosphatases And Methods For Processing Starch Using The Same, Matthew S. Gentry, Craig W. Vander Kooi

Molecular and Cellular Biochemistry Faculty Patents

The presently-disclosed subject matter includes thermophilic glucan phosphatase polypeptides. In some embodiments the polypeptide includes non-native laforin polypeptides, or fragments and/or variants thereof, and in some instances the polypeptide can alter the biophysical properties of starch in vitro or in planta. The presently-disclosed subject matter also includes isolated polynucleotides encoding the present polypeptides, methods for processing starch by exposing starch to the present polypeptides, and methods for making the present polypeptides.

Tissue Restricted Splice Junctions Originate Not Only From Tissue-Specific Gene Loci, But Gene Loci With A Broad Pattern Of Expression, Matthew S. Hestand, Zheng Zeng, Stephen J. Coleman, Jinze Liu, James N. Macleod

Maxwell H. Gluck Equine Research Center Faculty Publications

Cellular mechanisms that achieve protein diversity in eukaryotes are multifaceted, including transcriptional components such as RNA splicing. Through alternative splicing, a single protein-coding gene can generate multiple mRNA transcripts and protein isoforms, some of which are tissue-specific. We have conducted qualitative and quantitative analyses of the Bodymap 2.0 messenger RNA-sequencing data from 16 human tissue samples and identified 209,363 splice junctions. Of these, 22,231 (10.6%) were not previously annotated and 21,650 (10.3%) were expressed in a tissue-restricted pattern. Tissue-restricted alternative splicing was found to be widespread, with approximately 65% of expressed multi-exon genes containing at least one tissue-specific splice junction. …

Summer-Long Grazing Of High Vs. Low Endophyte (Neotyphodium Coenophialum)-Infected Tall Fescue By Growing Beef Steers Results In Distinct Temporal Blood Analyte Response Patterns, With Poor Correlation To Serum Prolactin Levels, Joshua J. Jackson, Merlin D. Lindemann, James A. Boling, James C. Matthews

Animal and Food Sciences Faculty Publications

Previously, we reported the effects of fescue toxicosis on developing Angus-cross steer growth, carcass, hepatic mRNA, and protein expression profiles of selected serum proteins, and blood clinical and chemical profiles, after summer-long grazing (85 days) of high endophyte (HE)- vs. low endophyte (LE)-infected fescue pastures. We now report the temporal development of acute, intermediate, and chronic responses of biochemical and clinical blood analytes determined at specified time intervals (period 1, day 0–36; period 2, day 37–58; and period 3, day 59–85). Throughout the trial, the alkaloid concentrations of the HE forage was consistently 19–25 times greater (P ≤ 0.002) …

Inter-Organizational Network Effects On The Implementation Of Public Health Services, Glen P. Mays

Health Management and Policy Presentations

Background: The Affordable Care Act created new incentives for hospitals, insurers, public health agencies, and others to contribute to disease prevention and health promotion activities, potentially changing inter-organizational relationships and expanding implementation of strategies that improve population health. This study uses data from the 1998-2014 National Longitudinal Survey of Public Health Systems to examine: (1) the extent and nature of change in inter-organizational contributions to public health activities; (2) whether network changes attenuate or exacerbate disparities in public health implementation across communities; and (3) how network changes affect preventable mortality and resource use.

Methods: We follow a longitudinal cohort of …

The Visual Priming Of Motion-Defined 3d Objects, Xiong Jiang, Yang Jiang, Raja Parasuraman

Behavioral Science Faculty Publications

The perception of a stimulus can be influenced by previous perceptual experience, a phenomenon known as perceptual priming. However, there has been limited investigation on perceptual priming of shape perception of three-dimensional object structures defined by moving dots. Here we examined the perceptual priming of a 3D object shape defined purely by motion-in-depth cues (i.e., Shape-From-Motion, SFM) using a classic prime-target paradigm. The results from the first two experiments revealed a significant increase in accuracy when a "cloudy" SFM stimulus (whose object structure was difficult to recognize due to the presence of strong noise) was preceded by an unambiguous SFM …

Renal Replacement Therapy In Patients With Left Ventricular Assist Device: What Do The Cardiologists Need To Know?, Hesham R. Omar

The VAD Journal

Renal failure after left ventricular assist device (LVAD) implantation occurs either due to worsening chronic kidney disease which is common in end-stage heart failure, or due to acute kidney injury in the peri-implantation period, and is associated with high morbidity and short-term mortality. The increased utilization of LVAD in refractory heart failure either as a bridge to transplantation or destination therapy will eventually create a population of patients with LVADs who are dialysis-dependent. There are multiple challenges encountered during dialysis of patients with LVADs including the unfamiliarity of nephrologists with the LVAD technology, difficulty in hemodynamic monitoring with continuous flow …

Estimated Probability Of Becoming Alcohol Dependent: Extending A Multiparametric Approach, Olga A. Vsevolozhskaya, James C. Anthony

Biostatistics Presentations

Background: United States (US) epidemiological studies suggest that for every 5-8 who start drinking alcoholic beverages, at least one drinker will develop an alcohol dependence (AD) syndrome within the first 10 years after onset of drinking (Lopez-Quintero et al., 2011; Wagner & Anthony, 2002). Recently, we described a multiparametric functional analysis approach for new research to estimate these transition probabilities with a one-dimensional function (1D; Vsevolozhskaya & Anthony, 2015). Here, we demonstrate extension of this analysis to two-dimensional (2D) functions that combine information about number of recent drinking days and number of drinks on the typical drinking day.

Methods: Data …

High-Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis And Method Of Generating The Same, Chang-Guo Zhan, Hoon Cho, Hsin-Hsiung Tai

Pharmaceutical Sciences Faculty Patents

A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, …

Chronic Ethanol Exposure Enhances The Aggressiveness Of Breast Cancer: The Role Of P38Γ, Mei Xu, Siying Wang, Zhenhua Ren, Jacqueline A. Frank, Xiuwei H. Yang, Zhuo Zhang, Zun-Ji Ke, Xianglin Shi, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the …

Anti-Cocaine Compositions And Treatment, Donald Landry, Chang-Guo Zhan, James H. Woods, Roger Sunahara, Diwahar L. Narasimhan, Joanne Macdonald, Victor Yang, Mei-Chuan Holden Ko, Shi-Xian Deng, John J. Tesmer, Tien-Yi Lee, Young Min Kwon, Daquan Gao

Pharmaceutical Sciences Faculty Patents

Embodiments of the invention disclosed herein generally relate to anti-cocaine therapeutics. Specifically, some embodiments of the invention relate to highly efficient, thermostable, and long-lasting cocaine esterase (CocE) mutants that can protect against the toxic and reinforcing effects of cocaine in subjects. Provided herein are mutant CocE polypeptides displaying thermostable esterase activity. Also provided are methods of treating cocaine-induced conditions in a subject in need via administration of mutant CocE as well as methods for high-throughput screening of candidate esterase polypeptides.

Systematic Review Of Ambulatory Transitional Care Management (Tcm) Visits On Hospital 30-Day Readmission Rates, Karen L. Roper, Jonathan Ballard, Wade Rankin, Roberto Cardarelli

Family and Community Medicine Faculty Publications

To reduce readmission rates and prevent adverse outcomes after discharge, hospitals have begun implementing "transitional care" initiatives. This systematic review identifies research on the particular set of services now reimbursable by Medicare (transitional care management [TCM]) and evaluates the studies for program effectiveness. Results of 3 databases were screened for peer-reviewed journal articles published between January 2004 and 2015 that report on readmissions of adults in the US health care system under the Medicare TCM bundle. ClinicalTrials.gov was queried for funded studies. Of 969 identified studies, 77 met inclusion criteria for relevance to transitional care and appropriateness of population and …

Chronic Systemic Immune Dysfunction In African-Americans With Small Vessel-Type Ischemic Stroke, Candice M. Brown, Cheryl D. Bushnell, Gregory P. Samsa, Larry B. Goldstein, Carol A. Colton

Neurology Faculty Publications

The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African-Americans with lacunar stroke (n = 30), and controls were age-matched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained > 6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide …

A Clinical Trial To Validate Event-Related Potential Markers Of Alzheimer's Disease In Outpatient Settings, Marco Cecchi, Dennis K. Moore, Carl H. Sadowsky, Paul R. Solomon, P. Murali Doraiswamy, Charles D. Smith, Gregory A. Jicha, Andrew E. Budson, Steven E. Arnold, Kalford C. Fadem

Neurology Faculty Publications

INTRODUCTION: We investigated whether event-related potentials (ERP) collected in outpatient settings and analyzed with standardized methods can provide a sensitive and reliable measure of the cognitive deficits associated with early Alzheimer's disease (AD).

METHODS: A total of 103 subjects with probable mild AD and 101 healthy controls were recruited at seven clinical study sites. Subjects were tested using an auditory oddball ERP paradigm.

RESULTS: Subjects with mild AD showed lower amplitude and increased latency for ERP features associated with attention, working memory, and executive function. These subjects also had decreased accuracy and longer reaction time in the target detection task …

Hybrid Diffuse Optical Techniques For Continuous Hemodynamic Measurement In Gastrocnemius During Plantar Flexion Exercise, Brad Henry, Mingjun Zhao, Yu Shang, Tim L. Uhl, D. Travis Thomas, Eleftherios S. Xenos, Sibu P. Saha, Guoqiang Yu

Physical Therapy Faculty Publications

Occlusion calibrations and gating techniques have been recently applied by our laboratory for continuous and absolute diffuse optical measurements of foreann muscle hemodynamics during handgrip exercises. The translation of these techniques from the foreann to the lower limb is the goal of this study as various diseases preferentially affect muscles in the lower extremity. This study adapted a hybrid near-infrared spectroscopy and diffuse correlation spectroscopy system with a gating algorithm to continuously quantify hemodynamic responses of medial gastrocnemius during plantar flexion exercises in 10 healthy subjects. The outcomes from optical measurement include oxy-, deoxy-, and total hemoglobin poncentrations, blood oxygen …

Reliability Of 3-Dimensional Measures Of Single-Leg Cross Drop Landing Across 3 Different Institutions: Implications For Multicenter Biomechanical And Epidemiological Research On Acl Injury Prevention, Christopher A. Dicesare, Nathaniel A. Bates, Kim D. Barber Foss, Staci M. Thomas, Samuel C. Wordeman, Dai Sugimoto, Benjamin D. Roewer, Jennifer M. Medina Mckeon, Stephanie Di Stasi, Brian W. Noehren, Kevin R. Ford, Adam W. Kiefer, Timothy E. Hewett, Gregory D. Myer

Physical Therapy Faculty Publications

Background: Anterior cruciate ligament (ACL) injuries are physically and financially devastating but affect a relatively small percentage of the population. Prospective identification of risk factors for ACL injury necessitates a large sample size; therefore, study of this injury would benefit from a multicenter approach.

Purpose: To determine the reliability of kinematic and kinetic measures of a single-leg cross drop task across 3 institutions.

Study Design: Controlled laboratory study.

Methods: Twenty-five female high school volleyball players participated in this study. Three-dimensional motion data of each participant performing the single-leg cross drop were collected at 3 institutions over a period of 4 …

Efficacy And Safety Of Vorapaxar In Non-St-Segment Elevation Acute Coronary Syndrome Patients Undergoing Noncardiac Surgery, Sean Van Diepen, Pierluigi Tricoci, Mohua Podder, Cynthia M. Westerhout, Philip E. Aylward, Claes Held, Frans Van De Werf, John Strony, Lars Wallentin, David J. Moliterno, Harvey D. White, Kenneth W. Mahaffey, Robert A. Harrington, Paul W. Armstrong

Gill Heart & Vascular Institute Faculty Publications

Background—Perioperative antiplatelet agents potentially increase bleeding after non–ST‐segment elevation (NSTE) acute coronary syndromes (ACS). The protease‐activated receptor 1 antagonist vorapaxar reduced cardiovascular events and was associated with increased bleeding versus placebo in NSTE ACS, but its efficacy and safety in noncardiac surgery (NCS) remain unknown. We aimed to evaluate ischemic, bleeding, and long‐term outcomes of vorapaxar in NCS after NSTE ACS.

Methods and Results—In the TRACER trial, 2202 (17.0%) patients underwent major or minor NCS after NSTE ACS over 1.5 years (median); continuing study treatment perioperatively was recommended. The primary ischemic end point for this analysis was cardiovascular …

Modulation Of Angiogenesis, Balamurali Krishna Ambati, Jayakrishna Ambati, Nirbhai Singh

Ophthalmology and Visual Science Faculty Patents

This invention relates to compounds, composJtwns, and methods for the treatment of traits, diseases and conditions that respond to the modulation of angiogenic growth factor bioavailability or biological activity.

Individual Responses For Muscle Activation, Repetitions, And Volume During Three Sets To Failure Of High- (80% 1rm) Versus Low-Load (30% 1rm) Forearm Flexion Resistance Exercise, Nathaniel D. M. Jenkins, Terry J. Housh, Samuel L. Buckner, Haley C. Bergstrom, Kristen C. Cochrane, Cory M. Smith, Ethan C. Hill, Richard J. Schmidt, Joel T. Cramer

Kinesiology and Health Promotion Faculty Publications

This study compared electromyographic (EMG) amplitude, the number of repetitions completed, and exercise volume during three sets to failure of high- (80% 1RM) versus low-load (30% 1RM) forearm flexion resistance exercise on a subject-by-subject basis. Fifteen men were familiarized, completed forearm flexion 1RM testing. Forty-eight to 72 h later, the subjects completed three sets to failure of dumbbell forearm flexion resistance exercise with 80% (n = 8) or 30% (n = 7) 1RM. EMG amplitude was calculated for every repetition, and the number of repetitions performed and exercise volume were recorded. During sets 1, 2, and 3, one …

Impact Of Sleep And Circadian Disruption On Energy Balance And Diabetes: A Summary Of Workshop Discussions, Deanna M. Arble, Joseph Bass, Cecilia Diniz Behn, Matthew P. Butler, Etienne Challet, Charles Czeisler, Christopher M. Depner, Joel Elmquist, Paul Franken, Michael A. Grandner, Erin C. Hanlon, Alex C. Keene, Michael J. Joyner, Ilia Karatsoreos, Philip A. Kern, Samuel Klein, Christopher J. Morris, Allan I. Pack, Satchidananda Panda, Louis J. Ptacek, Naresh M. Punjabi, Paolo Sassone-Corsi, Frank A. Scheer, Richa Saxena, Elizabeth R. Seaquest, Matthew S. Thimgan, Eve Van Cauter, Kenneth P. Wright

Clinical and Translational Science Faculty Publications

A workshop was held at the National Institute for Diabetes and Digestive and Kidney Diseases with a focus on the impact of sleep and circadian disruption on energy balance and diabetes. The workshop identified a number of key principles for research in this area and a number of specific opportunities. Studies in this area would be facilitated by active collaboration between investigators in sleep/circadian research and investigators in metabolism/diabetes. There is a need to translate the elegant findings from basic research into improving the metabolic health of the American public. There is also a need for investigators studying the impact …

Sustained Isometric Shoulder Contraction On Muscular Strength And Endurance: A Randomized Clinical Trial, Natalie L. Myers, Jenny L. Toonstra, Jacob S. Smith, Cooper A. Padgett, Tim L. Uhl

Physical Therapy Faculty Publications

BACKGROUND: The Advanced Throwers Ten Exercise Program incorporates sustained isometric contractions in conjunction with dynamic shoulder movements. It has been suggested that incorporating isometric holds may facilitate greater increases in muscular strength and endurance. However, no objective evidence currently exists to support this claim.

HYPOTHESIS/PURPOSE: The purpose of this research was to compare the effects of a sustained muscle contraction resistive training program (Advanced Throwers Ten Program) to a more traditional exercise training protocol to determine if increases in shoulder muscular strength and endurance occur in an otherwise healthy population. It was hypothesized that utilizing a sustained isometric …

Methylseleninic Acid Promotes Antitumour Effects Via Nuclear Foxo3a Translocation Through Akt Inhibition, Míriam Tarrado-Castellarnau, Roldán Cortés, Miriam Zanuy, Josep Tarragó-Celada, Ibrahim H. Polat, Richard Hill, Teresa W-M Fan, Wolfgang Link, Marta Cascante

Toxicology and Cancer Biology Faculty Publications

Selenium supplement has been shown in clinical trials to reduce the risk of different cancers including lung carcinoma. Previous studies reported that the antiproliferative and pro-apoptotic activities of methylseleninic acid (MSA) in cancer cells could be mediated by inhibition of the PI3K pathway. A better understanding of the downstream cellular targets of MSA will provide information on its mechanism of action and will help to optimize its use in combination therapies with PI3K inhibitors. For this study, the effects of MSA on viability, cell cycle, metabolism, apoptosis, protein and mRNA expression, and reactive oxygen species production were analysed in A549 …

Post Operative Fungal Endopthalmitis Due To Geotrichum Candidum, Thein Myint, Matthew J. Dykhuizen, Carolyn H. Mcdonald, Julie A. Ribes

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Geotrichum species have been rarely reported as the cause of sepsis, disseminated infection in immunosuppressed patients. The patient we describe developed indolent endophthalmitis four months after her routine right eye cataract surgery. The intraoperative sample from right vitreous fluid grew Geotrichum candidum. The patient underwent vitrectomy, artificial lens explantation and intravitreal injection of amphotericin B followed by oral voriconazole. Despite these interventions, she underwent enucleation. This is the first published case of Geotrichum candidum endophthalmitis.

Endoplasmic Reticulum Stress And Ethanol Neurotoxicity, Fanmuyi Yang, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Ethanol abuse affects virtually all organ systems and the central nervous system (CNS) is particularly vulnerable to excessive ethanol exposure. Ethanol exposure causes profound damages to both the adult and developing brain. Prenatal ethanol exposure induces fetal alcohol spectrum disorders (FASD) which is associated with mental retardation and other behavioral deficits. A number of potential mechanisms have been proposed for ethanol-induced brain damage; these include the promotion of neuroinflammation, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, and thiamine deficiency. The endoplasmic reticulum (ER) regulates posttranslational protein processing and transport. The accumulation of …

Utilizing Monte Carlo Simulations To Optimize Institutional Empiric Antipseudomonal Therapy, Sarah J. Tennant, Donna R. Burgess, Jeffrey M. Rybak, Craig A. Martin, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Pseudomonas aeruginosa is a common pathogen implicated in nosocomial infections with increasing resistance to a limited arsenal of antibiotics. Monte Carlo simulation provides antimicrobial stewardship teams with an additional tool to guide empiric therapy. We modeled empiric therapies with antipseudomonal β-lactam antibiotic regimens to determine which were most likely to achieve probability of target attainment (PTA) of ≥90%. Microbiological data for P. aeruginosa was reviewed for 2012. Antibiotics modeled for intermittent and prolonged infusion were aztreonam, cefepime, meropenem, and piperacillin/tazobactam. Using minimum inhibitory concentrations (MICs) from institution-specific isolates, and pharmacokinetic and pharmacodynamic parameters from previously published studies, a 10,000-subject Monte …

Editorial: Leading People - Managing Organizations: Contemporary Public Health Leadership, James W. Holsinger Jr., Erik L. Carlton, Emmanuel D. Jadhav

Preventive Medicine and Environmental Health Faculty Publications

Effectively leading people engaged in the practice of public health has never been more critical than in the early years of the twenty-first century. Likewise, effectively managing the organizations in which these individuals practice the various professional disciplines of public health has become increasing important and difficult. Taken together, leading the people and managing public health organizations requires well educated and appropriately trained public health leaders and managers. Although leadership is often viewed as one of the key attributes of management, not every great manager will be a great leader and vice versa. While some leaders may be born with …

Dopaminergic Modulation Of Medial Prefrontal Cortex Deactivation In Parkinson Depression, Anders H. Andersen, Charles D. Smith, John T. Slevin, Richard J. Kryscio, Catherine A. Martin, Frederick A. Schmitt, Lee X. Blonder

Neuroscience Faculty Publications

Parkinson's disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after …

Azithromycin Drives Alternative Macrophage Activation And Improves Recovery And Tissue Sparing In Contusion Spinal Cord Injury, Bei Zhang, William M. Bailey, Timothy J. Kopper, Michael B. Orr, David J. Feola, John C. Gensel

Spinal Cord and Brain Injury Research Center Faculty Publications

BACKGROUND: Macrophages persist indefinitely at sites of spinal cord injury (SCI) and contribute to both pathological and reparative processes. While the alternative, anti-inflammatory (M2) phenotype is believed to promote cell protection, regeneration, and plasticity, pro-inflammatory (M1) macrophages persist after SCI and contribute to protracted cell and tissue loss. Thus, identifying non-invasive, clinically viable, pharmacological therapies for altering macrophage phenotype is a challenging, yet promising, approach for treating SCI. Azithromycin (AZM), a commonly used macrolide antibiotic, drives anti-inflammatory macrophage activation in rodent models of inflammation and in humans with cystic fibrosis.

METHODS: We hypothesized that AZM treatment can alter …

Epithelial Neoplasia Coincides With Exacerbated Injury And Fibrotic Response In The Lungs Of Gprc5a-Knockout Mice Following Silica Exposure, Xiaofei Wang, Dongliang Xu, Yueling Liao, Shuangshuang Zhong, Hongyong Song, Beibei Sun, Binhua P. Zhou, Jiong Deng, Baohui Han

Markey Cancer Center Faculty Publications

Exposure to crystalline silica is suggested to increase the risk for a variety of lung diseases, including fibrosis and lung cancer. However, epidemiological evidences for the exposure-risk relationship are ambiguous and conflicting, and experimental study from a reliable animal model to explore the relationship is lacking. We reasoned that a mouse model that is sensitive to both lung injury and tumorigenesis would be appropriate to evaluate the exposure-risk relationship. Previously, we showed that, Gprc5a^-/- mice are susceptible to both lung tumorigenesis and endotoxin-induced acute lung injury. In this study, we investigated the biological consequences in Gprc5a^-/- mouse model …

A Combination Approach To Treating Fungal Infections, Sanjib K. Shrestha, Marina Y. Fosso, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

Azoles are antifungal drugs used to treat fungal infections such as candidiasis in humans. Their extensive use has led to the emergence of drug resistance, complicating antifungal therapy for yeast infections in critically ill patients. Combination therapy has become popular in clinical practice as a potential strategy to fight resistant fungal isolates. Recently, amphiphilic tobramycin analogues, C₁₂ and C₁₄, were shown to display antifungal activities. Herein, the antifungal synergy of C₁₂ and C₁₄ with four azoles, fluconazole (FLC), itraconazole (ITC), posaconazole (POS), and voriconazole (VOR), was examined against seven Candida albicans strains. All tested strains …