Medicine and Health Sciences Commons^™

Effects Of An Exogenous Ketone Supplement On Five‐Kilometer Running Performance, Philip J. Prins, Andrew P. Koutnik, Dominic P. D’Agostino, Christopher Q. Rogers, Jacob F. Seibert, Jillian A. Breckenridge, Daniel S. Jackson, Edward J. Ryan, Jeffrey D. Buxton, Dana L. Ault

Molecular Pharmacology & Physiology Faculty Publications

Numerous oral ketone supplements are marketed with the claim that they will rapidly induce ketosis and improve exercise performance. The purpose of this study was to assess exercise performance time and related physiological, metabolic and perceptual responses of recreational endurance runners after ingestion of a commercially available oral ketone supplement. Recreational endurance runners (n = 10; age: 20.8 ± 1.0 years; body mass: 68.9 ± 5.6 kg; height: 175.6 ± 4.9 cm) participated in a double-blind, crossover, repeated-measures study where they were randomized to 300 mg.kg-1 body weight of an oral β-hydroxybutyrate-salt + Medium Chain Triglyceride (βHB-salt+MCT) ketone supplement or …

Collagen Xii Is A Regulator Of Corneal Stroma Structure And Function, Mei Sun, Nabeel Zafrullah, Floriane Devaux, Chinda Hemmavanh, Sheila Adams, Noel M. Ziebarth, Manuel Koch, David E. Birk, Edgar M. Espana

Molecular Pharmacology & Physiology Faculty Publications

Purpose: The aim of this study was to determine the roles of collagen XII in the regulation of stromal hierarchical organization, keratocyte organization, and corneal mechanics.

Methods: The temporal and spatial expression of collagen XII at postnatal days 4, 10, 30, 90, and 150 were evaluated in wild-type (WT) mice. The role of collagen XII in hierarchical organization was analyzed by measuring fibril diameter and density, as well as stromal lamellar structure, within ultrastructural micrographs obtained from WT and collagen XII-deficient mice (Col12a1–/–). Keratocyte morphology and networks were assessed using actin staining with phalloidin and in vivo confocal …

Ketone Bodies Attenuate Wasting In Models Of Atrophy, Andrew P. Koutnik, Angela M. Poff, Nathan P. Ward, Janine M. Deblasi, Maricel A. Soliven, Matthew A. Romero, Paul A. Roberson, Carl D. Fox, Michael D. Roberts, Dominic P. D'Agostino

Molecular Pharmacology & Physiology Faculty Publications

Background: Cancer Anorexia Cachexia Syndrome (CACS) is a distinct atrophy disease negatively influencing multiple aspects of clinical care and patient quality of life. Although it directly causes 20% of all cancer-related deaths, there are currently no model systems that encompass the entire multifaceted syndrome, nor are there any effective therapeutic treatments.

Methods: A novel model of systemic metastasis was evaluated for the comprehensive CACS (metastasis, skeletal muscle and adipose tissue wasting, inflammation, anorexia, anemia, elevated protein breakdown, hypoalbuminemia, and metabolic derangement) in both males and females. Ex vivo skeletal muscle analysis was utilized to determine ubiquitin proteasome degradation pathway activation. …

The Real Culprit Behind Diabetic Nephropathy: Impaired Renal Autoregulation?, Ruisheng Liu

Molecular Pharmacology & Physiology Faculty Publications

No abstract provided.

Structural Homologies Between Phenformin, Lipitor And Gleevec Aim The Same Metabolic Oncotarget In Leukemia And Melanoma, Gábor Somlyai, T. Que Collins, Emmanuelle J. Meuillet, Patel Hitendra, Dominic P. D’Agostino, László G. Boros

Molecular Pharmacology & Physiology Faculty Publications

Phenformin’s recently demonstrated efficacy in melanoma and Gleevec’s demonstrated anti-proliferative action in chronic myeloid leukemia may lie within these drugs’ significant pharmacokinetics, pharmacodynamics and structural homologies, which are reviewed herein. Gleevec’s success in turning a fatal leukemia into a manageable chronic disease has been trumpeted in medical, economic, political and social circles because it is considered the first successful targeted therapy. Investments have been immense in omics analyses and while in some cases they greatly helped the management of patients, in others targeted therapies failed to achieve clinically stable recurrence-free disease course or to substantially extend survival. Nevertheless protein kinase …

Rnd3 As A Novel Target To Ameliorate Microvascular Leakage, Jerome W. Breslin, Dayle A. Daines, Travis M. Doggett, Kristine H. Kurtz, Flavia M. Souza-Smith, Xun E. Zhang, Mack H. Wu, Sarah Y. Yuan

Molecular Pharmacology & Physiology Faculty Publications

Background: Microvascular leakage of plasma proteins is a hallmark of inflammation that leads to tissue dysfunction. There are no current therapeutic strategies to reduce microvascular permeability. The purpose of this study was to identify the role of Rnd3, an atypical Rho family GTPase, in the control of endothelial barrier integrity. The potential therapeutic benefit of Rnd3 protein delivery to ameliorate microvascular leakage was also investigated.

Methods and Results: Using immunofluorescence microscopy, Rnd3 was observed primarily in cytoplasmic areas around the nuclei of human umbilical vein endothelial cells. Permeability to fluorescein isothiocyanate–albumin and transendothelial electrical resistance of human umbilical vein endothelial …

Dendritic And Langerhans Cells Respond To Aβ Peptides Differently: Implication For Ad Immunotherapy, Jiang Cheng, Xiaoyang Lin, David Morgan, Marcia Gordon, Xi Chen, Zhen-Hai Wang, Hai-Ning Li, Lan-Jie He, Shu-Feng Zhou, Chuanhai Cao

Molecular Pharmacology & Physiology Faculty Publications

Both wild-type and mutated beta-amyloid (Aβ) peptides can elicit an immune response when delivered subcutaneously. However, only mutated forms of Aβ can sensitize dendritic cells when administered intravenously or intraperitoneally. To understand the role of mutation and delivery routes in creating immune responses, and the function of dendritic cells as therapeutic agents, we used fluorescent-conjugated WT Aβ1-40 (WT40) and artificially mutated Aβ1-40 (22W40) peptides to treat dendritic and Langerhans cells from young and/or old mice at different time points. The cell types were analyzed by flow cytometry and confocal microscopy to identify differences in function and antigen presentation, and Luminex …

Female Rats Are More Susceptible To Central Nervous System Oxygen Toxicity Than Male Rats, Heather E. Held, Raffaele Pilla, Geoffrey E. Ciarlone, Carol S. Landon, Jay B. Dean

Molecular Pharmacology & Physiology Faculty Publications

Tonic–clonic seizures typify central nervous system oxygen toxicity (CNS-OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS-OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio-telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) …

Diverse Inflammatory Responses In Transgenic Mouse Models Of Alzheimer's Disease And The Effect Of Immunotherapy On These Responses, Donna M. Wilcock, Qun Zhao, Dave Morgan, Marcia N. Gordon, Angela Everhart, Joan G. Wilson, Jennifer E. Lee, Carol A. Colton

Molecular Pharmacology & Physiology Faculty Publications

While the presence of an inflammatory response in AD (Alzheimer's disease) is well known, the data on inflammation are conflicting, suggesting that inflammation either attenuates pathology, exacerbates it or has no effect. Our goal was to more fully characterize the inflammatory response in APP (amyloid precursor protein) transgenic mice with and without disease progression. In addition, we have examined how anti-Aβ (amyloid β-peptide) immunotherapy alters this inflammatory response. We have used quantitative RT–PCR (reverse transcription–PCR) and protein analysis to measure inflammatory responses ranging from proinflammatory to anti-inflammatory and repair factors in transgenic mice that develop amyloid deposits only …