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Articles 1 - 30 of 48
Full-Text Articles in Medical Physiology
Are E-Cigarettes A Safer Alternative? Revisiting The Cardiovascular Cost Of Nicotine Delivery, Jason D. Gardner
Are E-Cigarettes A Safer Alternative? Revisiting The Cardiovascular Cost Of Nicotine Delivery, Jason D. Gardner
School of Graduate Studies Faculty Publications
No abstract provided.
Selective Depletion Of Gut Gram-Negative Bacteria Attenuates Alcohol Binge-Induced Cardiovascular Dysfunction By Lowering Cardiac Anandamide Levels, Sarah E. Cohen, Meagan E. Donovan, Davin J. Gardner, Danielle Sambo, Seray B. Karagoz, Resat Cinar, David Goldman, Jason D. Gardner, Pal Pacher, Janos Paloczi
Selective Depletion Of Gut Gram-Negative Bacteria Attenuates Alcohol Binge-Induced Cardiovascular Dysfunction By Lowering Cardiac Anandamide Levels, Sarah E. Cohen, Meagan E. Donovan, Davin J. Gardner, Danielle Sambo, Seray B. Karagoz, Resat Cinar, David Goldman, Jason D. Gardner, Pal Pacher, Janos Paloczi
School of Graduate Studies Faculty Publications
Binge drinking contributes to an increasing number of emergency department visits in the United States. Previous work demonstrated that an alcohol binge impairs cardiac performance and exerts complex hemodynamic effects through the activation of the endocannabinoid-mediated cannabinoid type 1 receptor (CB1R) signaling pathway. Anandamide (AEA), an endogenous CB1R agonist, is synthesized in response to various stressors and tissue injury. However, the role of binge drinking in increasing myocardial AEA levels, which leads to CB1R-dependent cardiodepression, remains unclear. This work studied how endotoxins from intestinal Gram-negative bacteria affect myocardial AEA levels, which further induce CB1R-dependent cardiac dysfunction following acute alcohol intoxication. …
Prior Adolescent Oxycodone Exposure Enhances Pain Sensitivity Following Chronic Intermittent Ethanol In Adult Female Mice, Lisa L. Wilson, Lucas Albrechet-Souza, Linh Ha, Nicholas W. Gilpin, Tiffany A. Wills
Prior Adolescent Oxycodone Exposure Enhances Pain Sensitivity Following Chronic Intermittent Ethanol In Adult Female Mice, Lisa L. Wilson, Lucas Albrechet-Souza, Linh Ha, Nicholas W. Gilpin, Tiffany A. Wills
School of Graduate Studies Faculty Publications
The opioid crisis remains a critical public health concern, with rising rates of overdose and opioid use disorder. While opioids are effective for managing pain, both chronic use and withdrawal are associated with increased pain sensitivity. Although most prior research has focused on adults, opioid use during adolescence is common and linked to a heightened risk for developing alcohol use disorder and other forms of substance misuse. Like opioids, acute alcohol use can be analgesic, but chronic alcohol exposure and withdrawal lead to increased pain sensitivity. However, the interactive effects of adolescent opioid and adult alcohol exposure on pain remain …
Renal Denervation Improves Cardiac Function And Exercise Duration In A Miniswine Model Of Heart Failure With Preserved Ejection Fraction, David J. Lefer, Thomas E. Sharp, Amy L. Scarborough, Amelia G. Haydel, Sanjiv J. Shah, Zhen Li, Traci T. Goodchild
Renal Denervation Improves Cardiac Function And Exercise Duration In A Miniswine Model Of Heart Failure With Preserved Ejection Fraction, David J. Lefer, Thomas E. Sharp, Amy L. Scarborough, Amelia G. Haydel, Sanjiv J. Shah, Zhen Li, Traci T. Goodchild
School of Medicine Faculty Publications
Aims: Overactivity of the sympathetic nervous system is a common underlying mechanism in development and progression of several heart failure with preserved ejection fraction (HFpEF) comorbidities. Decreasing renal sympathetic nerve activity using catheter-based renal denervation (RDN) systems have shown efficacy in treating resistant hypertension and cardiac dysfunction in heart failure with reduced ejection fraction. The purpose of this study was to determine if modulation of renal sympathetic nerve activity by RDN improves cardiac function and exercise tolerance in a clinically-relevant minipig model of cardiometabolic HFpEF. Methods and results: Multiple HFpEF comorbidities were induced in adult female Göttingen minipigs by mineralocorticoid …
Intersection Of Alcohol Use, Pain Symptoms, And Negative Affect In Total Knee Arthroplasty Patients And People With Hiv, Taylor Fitzpatrick-Schmidt, Vinod Dasa, Claudia Leonardi, Tekeda F. Ferguson, David A. Welsh, Patricia E. Molina, Martin J.J. Ronis, Scott Edwards
Intersection Of Alcohol Use, Pain Symptoms, And Negative Affect In Total Knee Arthroplasty Patients And People With Hiv, Taylor Fitzpatrick-Schmidt, Vinod Dasa, Claudia Leonardi, Tekeda F. Ferguson, David A. Welsh, Patricia E. Molina, Martin J.J. Ronis, Scott Edwards
School of Medicine Faculty Publications
Alcohol is a well-known analgesic, although excessive alcohol use can lead to hyperalgesia and heightened negative affect. This cross-sectional study examined associations between alcohol use, self-reported pain, and negative affective symptoms in two distinct cohorts of patients vulnerable to chronic pain: individuals undergoing total knee arthroplasty (TKA) surgery and a cohort of people with HIV (PWH). Participants were enrolled in two clinical studies: a retrospective study of patients undergoing TKA and a longitudinal study of PWH, the New Orleans Alcohol Use in HIV (NOAH) cohort. Based on the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C) score, participants in both …
Heart Failure In Black Populations: Epidemiology, Pathophysiology, And Treatment Disparities, Kazi N. Islam, Rahib K. Islam, Ivan Nguyen, Yasmeen Magherahabed, Humza Pirzadah, M. Bazlur Rashid
Heart Failure In Black Populations: Epidemiology, Pathophysiology, And Treatment Disparities, Kazi N. Islam, Rahib K. Islam, Ivan Nguyen, Yasmeen Magherahabed, Humza Pirzadah, M. Bazlur Rashid
School of Medicine Faculty Publications
Heart failure (HF) remains a significant health challenge globally, placing a heavy burden on individuals, families, and healthcare systems. The prevalence of HF continues to rise, posing substantial public health concerns. This burden is particularly pronounced among the Black Population, who face higher prevalence, earlier onset, and greater severity of HF compared to other racial and ethnic groups. This review explores the multifaceted landscape of HF in Black individuals by examining epidemiological patterns, pathophysiological mechanisms, clinical presentations, treatment disparities, and clinical outcomes. Black individuals exhibit distinct pathophysiological characteristics, such as genetic variations contributing to heightened susceptibility and severity of HF. …
Genetically Conditioned Interaction Among Microrna-155, Alpha-Klotho, And Intra-Renal Ras In Male Rats: Link To Ckd Progression, Lisa M. Harrison-Bernard, L. Raij, R. X. Tian, E. A. Jaimes
Genetically Conditioned Interaction Among Microrna-155, Alpha-Klotho, And Intra-Renal Ras In Male Rats: Link To Ckd Progression, Lisa M. Harrison-Bernard, L. Raij, R. X. Tian, E. A. Jaimes
School of Graduate Studies Faculty Publications
Incident chronic kidney disease (CKD) varies in populations with hypertension of similar severity. Proteinuria promotes CKD progression in part due to activation of plasminogen to plasmin in the podocytes, resulting in oxidative stress-mediated injury. Additional mechanisms include deficiency of renal alpha-klotho, that inhibits Wnt/beta-catenin, an up regulator of intra-renal renin angiotensin system (RAS) genes. Alpha-klotho deficiency therefore results in upregulation of the intra-renal RAS via Wnt/beta-catenin. In hypertensive, Dahl salt sensitive (DS) and spontaneously hypertensive rats (SHR), we investigated renal and vascular injury, miR-155, AT1R, alpha-klotho, and TNF-α. Hypertensive high salt DS (DS-HS), but not SHR developed proteinuria, plasminuria, and …
Epigenetic Mechanisms Differentially Regulate Blood Pressure And Renal Dysfunction In Male And Female Npr1 Haplotype Mice, Prerna Kumar, Kandasamy Neelamegam, Chandramohan Ramasamy, Ramachandran Samivel, Huijing Xia, Daniel R. Kapusta, Kailash N. Pandey
Epigenetic Mechanisms Differentially Regulate Blood Pressure And Renal Dysfunction In Male And Female Npr1 Haplotype Mice, Prerna Kumar, Kandasamy Neelamegam, Chandramohan Ramasamy, Ramachandran Samivel, Huijing Xia, Daniel R. Kapusta, Kailash N. Pandey
School of Graduate Studies Faculty Publications
We determined the epigenetic mechanisms regulating mean arterial pressure (MAP) and renal dysfunction in guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene-targeted mice. The Npr1 (encoding NPRA) gene-targeted mice were treated with class 1 specific histone deacetylase inhibitor (HDACi) mocetinostat (MGCD) to determine the epigenetic changes in a sex-specific manner. Adult male and female Npr1 haplotype (1-copy; Npr1+/−), wild-type (2-copy; Npr1+/+), and gene-duplicated heterozygous (3-copy; Npr1++/+) mice were intraperitoneally injected with MGCD (2 mg/kg) for 14 days. BP, renal function, histopathology, and epigenetic changes were measured. One-copy male mice showed significantly increased MAP, renal dysfunction, and fibrosis than 2-copy and 3-copy mice. …
Podocyte Cell-Specific Npr1 Is Required For Blood Pressure And Renal Homeostasis In Male And Female Mice: Role Of Sex-Specific Differences, Chandramohan Ramasamy, Kandasamy Neelamegam, Samivel Ramachandran, Huijing Xia, Daniel R. Kapusta, Farhad R. Danesh, Kailash N. Pandey
Podocyte Cell-Specific Npr1 Is Required For Blood Pressure And Renal Homeostasis In Male And Female Mice: Role Of Sex-Specific Differences, Chandramohan Ramasamy, Kandasamy Neelamegam, Samivel Ramachandran, Huijing Xia, Daniel R. Kapusta, Farhad R. Danesh, Kailash N. Pandey
School of Graduate Studies Faculty Publications
Atrial and brain natriuretic peptides (ANP and BNP) bind to guanylyl cyclase A/natriuretic peptide receptor A (GC-A/NPRA), stimulating natriuresis and diuresis and reducing blood pressure (BP), but the role of ANP/NPRA signaling in podocytes (highly specialized epithelial cells covering the outer surfaces of renal glomerular capillaries) remains unclear. This study aimed to determine the effect of conditional deletion of podocyte-specific Npr1 (encoding NPRA) gene knockout (KO) in male and female mice. Tamoxifen-treated wild-type control (PD Npr1 f/f; WT), heterozygous (PD-Cre-Npr1 f/+; HT), and KO (PD-Cre-Npr1 f/-) mice were fed a normal-, low-, or high-salt diet for 4 wk. Podocytes isolated …
Adjunctive Therapy With An Oral H2s Donor Provides Additional Therapeutic Benefit Beyond Sglt2 Inhibition In Cardiometabolic Heart Failure With Preserved Ejection Fraction, Jake E. Doiron, Huijing Xia, Xiaoman Yu, Alexandra R. Nevins, Kyle B. Lapenna, Thomas E. Sharp, Traci T. Goodchild, Timothy D. Allerton, Mona Elgazzaz, Eric Lazartigues, Sanjiv J. Shah, Zhen Li, David J. Lefer
Adjunctive Therapy With An Oral H2s Donor Provides Additional Therapeutic Benefit Beyond Sglt2 Inhibition In Cardiometabolic Heart Failure With Preserved Ejection Fraction, Jake E. Doiron, Huijing Xia, Xiaoman Yu, Alexandra R. Nevins, Kyle B. Lapenna, Thomas E. Sharp, Traci T. Goodchild, Timothy D. Allerton, Mona Elgazzaz, Eric Lazartigues, Sanjiv J. Shah, Zhen Li, David J. Lefer
School of Graduate Studies Faculty Publications
Background and Purpose: Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a potent therapy for heart failure with preserved ejection fraction (HFpEF). Hydrogen sulphide (H2S), a well-studied cardioprotective agent, could be beneficial in HFpEF. SGLT2i monotherapy and combination therapy involving an SGLT2i and H2S donor in two preclinical models of cardiometabolic HFpEF was investigated. Experimental Approach: Nine-week-old C57BL/6N mice received L-NAME and a 60% high fat diet for five weeks. Mice were then randomized to either control, SGLT2i monotherapy or SGLT2i and H2S donor, SG1002, for five additional weeks. Ten-week-old ZSF1 obese rats were randomized to control, SGLT2i or …
The Impact Of Childhood Adversity On Life Course Alcohol Use Patterns And Health Status Among People Living With Hiv, Rayna E. Gasik, Aubrey Spriggs Madkour, Simone J. Skeen, Gretchen Clum, Tishawn Francis, Erica Felker-Kantor, Tekeda Ferguson, David A. Welsh, Patricia E. Molina, Katherine P. Theall
The Impact Of Childhood Adversity On Life Course Alcohol Use Patterns And Health Status Among People Living With Hiv, Rayna E. Gasik, Aubrey Spriggs Madkour, Simone J. Skeen, Gretchen Clum, Tishawn Francis, Erica Felker-Kantor, Tekeda Ferguson, David A. Welsh, Patricia E. Molina, Katherine P. Theall
School of Public Health Faculty Publications
Adverse childhood experiences (ACEs) and financial hardship are associated with increased likelihood of heavier alcohol use and health challenges in adulthood among persons living with HIV (PWH). We examined whether retrospectively captured lifetime drinking trajectories are a pathway through which childhood hardships affect current health in a sample of 365 adult PWH. Childhood economic hardship and ACEs were used as main predictors. Measures of alcohol use included age at first drink and lifetime drinking trajectories. Health indicators included health-related quality of life, frailty, number of comorbidities, and symptoms of anxiety, depression, and post-traumatic stress disorder (PTSD). Structural equation modeling (SEM) …
Does The Use Of Double Hormone Replacement Therapy For Trauma Patient Organ Donors Improve Organ Recovery For Transplant, Eden M. Gallegos, Tanner Reed, Paige Deville, Blake Platt, Claudia Leonardi, Lillian Bellfi, Jessica Dufrene, Saad Chaudhary, John Hunt, Lance Stuke, Patrick Greiffenstein, Jonathan Schoen, Alan Marr, Anil Paramesh, Alison A. Smith
Does The Use Of Double Hormone Replacement Therapy For Trauma Patient Organ Donors Improve Organ Recovery For Transplant, Eden M. Gallegos, Tanner Reed, Paige Deville, Blake Platt, Claudia Leonardi, Lillian Bellfi, Jessica Dufrene, Saad Chaudhary, John Hunt, Lance Stuke, Patrick Greiffenstein, Jonathan Schoen, Alan Marr, Anil Paramesh, Alison A. Smith
School of Graduate Studies Faculty Publications
BACKGROUND With an ongoing demand for transplantable organs, optimization of donor management protocols, specifically in trauma populations, is important for obtaining a high yield of viable organs per patient. Endocrine management of brain-dead potential organ donors (BPODs) is controversial, leading to heterogeneous clinical management approaches. Previous studies have shown that when levothyroxine was combined with other treatments, including steroids, vasopressin, and insulin, BPODs had better organ recovery and survival outcomes were increased for transplant recipients. AIM To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients. METHODS A retrospective review …
Transcriptomic Signature, Bioactivity And Safety Of A Non-Hepatotoxic Analgesic Generating Am404 In The Midbrain Pag Region, Hernan A. Bazan, Surjyadipta Bhattacharjee, Madigan M. Reid, Bokkyoo Jun, Connor Polk, Madeleine Strain, Linsey A. St Pierre, Neehar Desai, Patrick W. Daly, Jessica A. Cucinello-Ragland, Scott Edwards, Javier Recio, Julio Alvarez-Builla, James J. Cai, Nicolas G. Bazan
Transcriptomic Signature, Bioactivity And Safety Of A Non-Hepatotoxic Analgesic Generating Am404 In The Midbrain Pag Region, Hernan A. Bazan, Surjyadipta Bhattacharjee, Madigan M. Reid, Bokkyoo Jun, Connor Polk, Madeleine Strain, Linsey A. St Pierre, Neehar Desai, Patrick W. Daly, Jessica A. Cucinello-Ragland, Scott Edwards, Javier Recio, Julio Alvarez-Builla, James J. Cai, Nicolas G. Bazan
School of Medicine Faculty Publications
Safe and effective pain management is a critical healthcare and societal need. The potential for acute liver injury from paracetamol (ApAP) overdose; nephrotoxicity and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use; and opioids’ addiction are unresolved challenges. We developed SRP-001, a non-opioid and non-hepatotoxic small molecule that, unlike ApAP, does not produce the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI) and preserves hepatic tight junction integrity at high doses. CD-1 mice exposed to SRP-001 showed no mortality, unlike a 70% mortality observed with increasing equimolar doses of ApAP within 72 h. SRP-001 and ApAP have comparable antinociceptive effects, including the complete …
Standard Rodent Diets Differentially Impact Alcohol Consumption, Preference, And Gut Microbiome Diversity, Aline Zaparte, Evan Dore, Selby White, Franciely Paliarin, Cameron Gabriel, Katherine Copenhaver, Samhita Basavanhalli, Emily Garcia, Rishith Vaddavalli, Meng Luo, Christopher M. Taylor, David Allen Welsh, Rajani Maiya
Standard Rodent Diets Differentially Impact Alcohol Consumption, Preference, And Gut Microbiome Diversity, Aline Zaparte, Evan Dore, Selby White, Franciely Paliarin, Cameron Gabriel, Katherine Copenhaver, Samhita Basavanhalli, Emily Garcia, Rishith Vaddavalli, Meng Luo, Christopher M. Taylor, David Allen Welsh, Rajani Maiya
School of Graduate Studies Faculty Publications
Alcohol use disorder (AUD) is a complex and widespread disease with limited pharmacotherapies. Preclinical animal models of AUD use a variety of voluntary alcohol consumption procedures to recapitulate different phases of AUD, including binge alcohol consumption and dependence. However, voluntary alcohol consumption in mice is widely variable, making it difficult to reproduce results across labs. Accumulating evidence indicates that different brands of commercially available rodent chow can profoundly influence alcohol intake. In this study, we investigated the effects of three commercially available and widely used rodent diet formulations on alcohol consumption and preference in C57BL/6 J mice using the 24 …
Brain-Specific Serine/Threonine-Protein Kinase 1 Is A Substrate Of Protein Kinase C Epsilon Involved In Sex-Specific Ethanol And Anxiety Phenotypes, Michael P. Dugan, Rajani Maiya, Caleb Fleischer, Michal Bajo, Angela E. Snyder, Ashwin Koduri, Sathvik Srinivasan, Marisa Roberto, Robert O. Messing
Brain-Specific Serine/Threonine-Protein Kinase 1 Is A Substrate Of Protein Kinase C Epsilon Involved In Sex-Specific Ethanol And Anxiety Phenotypes, Michael P. Dugan, Rajani Maiya, Caleb Fleischer, Michal Bajo, Angela E. Snyder, Ashwin Koduri, Sathvik Srinivasan, Marisa Roberto, Robert O. Messing
School of Graduate Studies Faculty Publications
Protein kinase C epsilon (PKCε) regulates behavioural responses to ethanol and plays a role in anxiety-like behaviour, but knowledge is limited on downstream substrates of PKCε that contribute to these behaviours. We recently identified brain-specific serine/threonine-protein kinase 1 (BRSK1) as a substrate of PKCε. Here, we test the hypothesis that BRSK1 mediates responses to ethanol and anxiety-like behaviours that are also PKCε dependent. We used in vitro kinase assays to further validate BRSK1 as a substrate of PKCε and used Brsk1−/− mice to assess the role of BRSK1 in ethanol- and anxiety-related behaviours and in physiological responses to ethanol. We …
Alcohol Impairs Bioenergetics And Differentiation Capacity Of Myoblasts From Simian Immunodeficiency Virus-Infected Female Macaques, Danielle E. Levitt, Brianna L. Bourgeois, Keishla M. Rodríguez-Graciani, Patricia E. Molina, Liz Simon
Alcohol Impairs Bioenergetics And Differentiation Capacity Of Myoblasts From Simian Immunodeficiency Virus-Infected Female Macaques, Danielle E. Levitt, Brianna L. Bourgeois, Keishla M. Rodríguez-Graciani, Patricia E. Molina, Liz Simon
School of Graduate Studies Faculty Publications
Alcohol misuse and HIV independently induce myopathy. We previously showed that chronic binge alcohol (CBA) administration, with or without simian immunodeficiency virus (SIV), decreases differentiation capacity of male rhesus macaque myoblasts. We hypothesized that short-term alcohol and CBA/SIV would synergistically decrease differentiation capacity and impair bioenergetic parameters in female macaque myoblasts. Myoblasts from naïve (CBA−/SIV−), vehicle [VEH]/SIV, and CBA/SIV (N = 4–6/group) groups were proliferated (3 days) and differentiated (5 days) with 0 or 50 mM ethanol (short-term). CBA/SIV decreased differentiation and increased non-mitochondrial oxygen consumption rate (OCR) versus naïve and/or VEH/SIV. Short-term alcohol decreased differentiation; increased maximal and non-mitochondrial …
Early Renal Denervation Attenuates Cardiac Dysfunction In Heart Failure With Preserved Ejection Fraction, Jake E. Doiron, Zhen Li, Xiaoman Yu, Kyle B. Lapenna, Heather Quiriarte, Timothy D. Allerton, Kashyap Koul, Andrew Malek, Sanjiv J. Shah, Thomas E. Sharp, Traci T. Goodchild, Daniel R. Kapusta, David J. Lefer
Early Renal Denervation Attenuates Cardiac Dysfunction In Heart Failure With Preserved Ejection Fraction, Jake E. Doiron, Zhen Li, Xiaoman Yu, Kyle B. Lapenna, Heather Quiriarte, Timothy D. Allerton, Kashyap Koul, Andrew Malek, Sanjiv J. Shah, Thomas E. Sharp, Traci T. Goodchild, Daniel R. Kapusta, David J. Lefer
School of Graduate Studies Faculty Publications
BACKGROUND: The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression. METHODS AND RESULTS: Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF-RDN) or sham procedure at either 8 weeks or 20 weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation …
Effects Of Metformin On Glucose Metabolism And Mitochondrial Function In Patients With Obstructive Sleep Apnea: A Pilot Randomized Trial, Elizabeth R.M. Zunica, Elizabeth C. Heintz, Wagner S. Dantas, R. Caitlin Hebert, Ma Kayla Tanksley, Robbie A. Beyl, Edward C. Mader, John P. Kirwan, Christopher L. Axelrod, Prachi Singh
Effects Of Metformin On Glucose Metabolism And Mitochondrial Function In Patients With Obstructive Sleep Apnea: A Pilot Randomized Trial, Elizabeth R.M. Zunica, Elizabeth C. Heintz, Wagner S. Dantas, R. Caitlin Hebert, Ma Kayla Tanksley, Robbie A. Beyl, Edward C. Mader, John P. Kirwan, Christopher L. Axelrod, Prachi Singh
School of Medicine Faculty Publications
Obstructive sleep apnea (OSA) is associated with increased risk for diabetes, and standard treatment with positive airway pressure (PAP) device shows inconsistent effects on glucose metabolism. Metformin is known to treat and prevent diabetes, but its effects on skeletal muscle mitochondrial function are not completely understood. Here, we evaluate the effects of metformin on glucose metabolism and skeletal muscle mitochondrial function in patients with OSA. Sixteen adults with obesity (50.9 ± 6.7 years, BMI: 36.5 ± 2.9 kg/m2) and moderate-to-severe OSA were provided with PAP treatment and randomized to 3 months of placebo (n = 8) or metformin (n = …
Using Phosphatidylethanol As An Adjunct To Self-Reported Alcohol Use Improves Identification Of Liver Fibrosis Risk, Pamela M. Murnane, Majid Afshar, Gabriel Chamie, Robert L. Cook, Tekeda Ferguson, Lamia Y. Haque, Karen R. Jacobson, Amy C. Justice, Theresa W. Kim, Mandana Khalili, Evgeny Krupitsky, Kathleen A. Mcginnis, Patricia Molina, Winnie R. Muyindike, Bronwyn Myers, Veronica L. Richards, Kaku So-Armah, Scott Stewart, Mark S. Sulkowski, Phyllis C. Tien, Judith A. Hahn
Using Phosphatidylethanol As An Adjunct To Self-Reported Alcohol Use Improves Identification Of Liver Fibrosis Risk, Pamela M. Murnane, Majid Afshar, Gabriel Chamie, Robert L. Cook, Tekeda Ferguson, Lamia Y. Haque, Karen R. Jacobson, Amy C. Justice, Theresa W. Kim, Mandana Khalili, Evgeny Krupitsky, Kathleen A. Mcginnis, Patricia Molina, Winnie R. Muyindike, Bronwyn Myers, Veronica L. Richards, Kaku So-Armah, Scott Stewart, Mark S. Sulkowski, Phyllis C. Tien, Judith A. Hahn
School of Public Health Faculty Publications
Introduction: Accurate assessment of alcohol use informs prevention and management of liver disease. We examined whether phosphatidylethanol (PEth, an alcohol metabolite) blood concentrations are associated with liver fibrosis risk independently of self-reported alcohol use, among persons with and without HIV. Methods: We pooled individual-level data from 12 studies from the United States, Russia, Uganda, and South Africa with PEth, AUDIT-C (Alcohol Use Disorders Identification Test-Consumption), and FIB-4 measurements. We conducted mixed-effects logistic regression of the relationship between PEth and AUDIT-C as continuous variables (after checking linearity), with high FIB-4 ( ≥ 2.67). We divided PEth (range 0-1000) by 83.3 to …
Validating Osteological Correlates For The Hepatic Piston In The American Alligator (Alligator Mississippiensis), Clinton A. Grand Pre, William Thielicke, Raul E. Diaz, Brandon P. Hedrick, Ruth M. Elsey, Emma R. Schachner
Validating Osteological Correlates For The Hepatic Piston In The American Alligator (Alligator Mississippiensis), Clinton A. Grand Pre, William Thielicke, Raul E. Diaz, Brandon P. Hedrick, Ruth M. Elsey, Emma R. Schachner
School of Graduate Studies Faculty Publications
Unlike the majority of sauropsids, which breathe primarily through costal and abdominal muscle contractions, extant crocodilians have evolved the hepatic piston pump, a unique additional ventilatory mechanism powered by the diaphragmaticus muscle. This muscle originates from the bony pelvis, wrapping around the abdominal viscera, extending cranially to the liver. The liver then attaches to the caudal margin of the lungs, resulting in a sub-fusiform morphology for the entire ‘‘pulmo-hepatic-diaphragmatic’’ structure. When the diaphragmaticus muscle contracts during inspiration, the liver is pulled caudally, lowering pressure in the thoracolumbar cavity, and inflating the lungs. It has been established that the hepatic piston …
Editorial; Biophysics Approaches To Investigate Multi-Organ Alcohol-Induced Damage, Janos Paloczi, Youngchan Kim
Editorial; Biophysics Approaches To Investigate Multi-Organ Alcohol-Induced Damage, Janos Paloczi, Youngchan Kim
School of Graduate Studies Faculty Publications
No abstract provided.
Abstinence Restores Cardiac Function In Mice With Established Alcohol-Induced Cardiomyopathy, Joshua M. Edavettal, Nicholas R. Harris, Sarah E. Cohen, Janos Paloczi, Bysani Chandrasekar, Jason D. Gardner
Abstinence Restores Cardiac Function In Mice With Established Alcohol-Induced Cardiomyopathy, Joshua M. Edavettal, Nicholas R. Harris, Sarah E. Cohen, Janos Paloczi, Bysani Chandrasekar, Jason D. Gardner
School of Graduate Studies Faculty Publications
Alcohol-induced cardiomyopathy (ACM) has a poor prognosis with up to a 50% chance of death within four years of diagnosis. There are limited studies investigating the potential of abstinence for promoting repair after alcohol-induced cardiac damage, particularly in a controlled preclinical study design. Here, we developed an exposure protocol that led to significant decreases in cardiac function in C57BL6/J mice within 30 days; dP/dt max decreased in the mice fed alcohol for 30 days (8054 ± 664.5 mmHg/s compared to control mice: 11,188 ± 724.2 mmHg/s, p < 0.01), and the dP/dt min decreased, as well (−7711 ± 561 mmHg/s compared to control mice: −10,147 ± 448.2 mmHg/s, p < 0.01). Quantitative PCR was used to investigate inflammatory and fibrotic biomarkers, while histology was used to depict overt changes in cardiac fibrosis. We observed a complete recovery of function after abstinence (dP/dt max increased from 8054 ± 664 mmHg/s at 30 days to 11,967 ± 449 mmHg/s after abstinence, p < 0.01); further, both inflammatory and fibrotic biomarkers decreased after abstinence. These results lay the groundwork for future investigation of the molecular mechanisms underlying recovery from alcohol-induced damage in the heart.
Prefrontal Cortex Glutamatergic Adaptations In A Mouse Model Of Alcohol Use Disorder, Mahum T. Siddiqi, Dhruba Podder, Amanda R. Pahng, Alexandria C. Athanason, Tali Nadav, Chelsea Cates-Gatto, Max Kreifeldt, Candice Contet, Amanda J. Roberts, Scott Edwards, Marisa Roberto, Florence P. Varodayan
Prefrontal Cortex Glutamatergic Adaptations In A Mouse Model Of Alcohol Use Disorder, Mahum T. Siddiqi, Dhruba Podder, Amanda R. Pahng, Alexandria C. Athanason, Tali Nadav, Chelsea Cates-Gatto, Max Kreifeldt, Candice Contet, Amanda J. Roberts, Scott Edwards, Marisa Roberto, Florence P. Varodayan
School of Graduate Studies Faculty Publications
Alcohol use disorder (AUD) produces cognitive deficits, indicating a shift in prefrontal cortex (PFC) function. PFC glutamate neurotransmission is mostly mediated by α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid-type ionotropic receptors (AMPARs); however preclinical studies have mostly focused on other receptor subtypes. Here we examined the impact of early withdrawal from chronic ethanol on AMPAR function in the mouse medial PFC (mPFC). Dependent male C57BL/6J mice were generated using the chronic intermittent ethanol vapor-two bottle choice (CIE-2BC) paradigm. Non-dependent mice had access to water and ethanol bottles but did not receive ethanol vapor. Naïve mice had no ethanol exposure. We used patch-clamp electrophysiology to measure …
Traumatic Stress-Induced Increases In Anxiety-Like Behavior And Alcohol Self-Administration Are Mediated By Central Amygdala Crf1 Neurons That Project To The Lateral Hypothalamus, Marcus M. Weera, Daniel A. Webster, Rosetta S. Shackett, Federica Benvenuti, Jason W. Middleton, Nicholas W. Gilpin
Traumatic Stress-Induced Increases In Anxiety-Like Behavior And Alcohol Self-Administration Are Mediated By Central Amygdala Crf1 Neurons That Project To The Lateral Hypothalamus, Marcus M. Weera, Daniel A. Webster, Rosetta S. Shackett, Federica Benvenuti, Jason W. Middleton, Nicholas W. Gilpin
School of Graduate Studies Faculty Publications
Avoidance stress coping, defined as persistent internal and/or external avoidance of stress-related stimuli, is a key feature of anxiety- and stress-related disorders, and contributes to increases in alcohol misuse after stress exposure. Previous work using a rat model of predator odor stress avoidance identified corticotropin-releasing factor (CRF) signaling via CRF type-1 receptors (CRF1) in the central amygdala (CeA), as well as CeA projections to the lateral hypothalamus (LH) as key mediators of conditioned avoidance of stress-paired contexts and/or increased alcohol drinking after stress. Here, we report that CRF1-expressing CeA cells that project to the LH are preferentially activated in male …
Acute Ethanol Modulates Synaptic Inhibition In The Basolateral Amygdala Via Rapid Nlrp3 Inflammasome Activation And Regulates Anxiety-Like Behavior In Rats, Soumyabrata Munshi, Lucas Albrechet-Souza, Raoni Conceição Dos-Santos, Claire E. Stelly, Maria E. Secci, Nicholas W. Gilpin, Jeffrey G. Tasker
Acute Ethanol Modulates Synaptic Inhibition In The Basolateral Amygdala Via Rapid Nlrp3 Inflammasome Activation And Regulates Anxiety-Like Behavior In Rats, Soumyabrata Munshi, Lucas Albrechet-Souza, Raoni Conceição Dos-Santos, Claire E. Stelly, Maria E. Secci, Nicholas W. Gilpin, Jeffrey G. Tasker
School of Graduate Studies Faculty Publications
Chronic alcohol exposure leads to a neuroinflammatory response involving activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and pro-inflammatory cytokine production. Acute ethanol (EtOH) exposure activates GABAergic synapses in the central and basolateral amygdala (BLA) ex vivo, but whether this rapid modulation of synaptic inhibition is due to an acute inflammatory response and alters anxiety-like behavior in male and female animals is not known. Here, we tested the hypotheses that acute EtOH facilitates inhibitory synaptic transmission in the BLA by activating the NLRP3 inflammasome-dependent acute inflammatory response, that the alcohol-induced increase in inhibition is cell type- and …
Human Alcohol-Microbiota Mice Have Increased Susceptibility To Bacterial Pneumonia, Kelly C. Cunningham, Deandra R. Smith, Daniel N. Villageliú, Christi M. Ellis, Amanda E. Ramer-Tait, Jeffrey D. Price, Todd A. Wyatt, Daren L. Knoell, Mystera M. Samuelson, Patricia E. Molina, David A. Welsh, Derrick R. Samuelson
Human Alcohol-Microbiota Mice Have Increased Susceptibility To Bacterial Pneumonia, Kelly C. Cunningham, Deandra R. Smith, Daniel N. Villageliú, Christi M. Ellis, Amanda E. Ramer-Tait, Jeffrey D. Price, Todd A. Wyatt, Daren L. Knoell, Mystera M. Samuelson, Patricia E. Molina, David A. Welsh, Derrick R. Samuelson
School of Medicine Faculty Publications
Preclinical studies have shown that chronic alcohol abuse leads to alterations in the gastrointestinal microbiota that are associated with behavior changes, physiological alterations, and immunological effects. However, such studies have been limited in their ability to evaluate the direct effects of alcohol-associated dysbiosis. To address this, we developed a humanized alcohol-microbiota mouse model to systematically evaluate the immunological effects of chronic alcohol abuse mediated by intestinal dysbiosis. Germ-free mice were colonized with human fecal microbiota from individuals with high and low Alcohol Use Disorders Identification Test (AUDIT) scores and bred to produce human alcohol-associated microbiota or human control-microbiota F1 progenies. …
Mediation Of Bmi On 25-Hydroxyvitamin D Levels In U.S. Adults With Sugar-Sweetened Beverages Consumption, Wei Ting Lin, Gabrielle V. Gonzalez, Yu Hsiang Kao, Hui Yi Lin, Mirandy S. Li, David W. Seal, Chien Hung Lee, Chih Yang Hu, Lei Shih Chen, Tung Sung Tseng
Mediation Of Bmi On 25-Hydroxyvitamin D Levels In U.S. Adults With Sugar-Sweetened Beverages Consumption, Wei Ting Lin, Gabrielle V. Gonzalez, Yu Hsiang Kao, Hui Yi Lin, Mirandy S. Li, David W. Seal, Chien Hung Lee, Chih Yang Hu, Lei Shih Chen, Tung Sung Tseng
School of Public Health Faculty Publications
Body mass index (BMI) as well as sugar-sweetened beverages (SSB) has been suggested to independently decrease 25-hydroxyvitamin D (25(OH)D). However, the relationship between SSB, BMI, and 25(OH)D is uncertain. This study aimed to investigate the potential mediating role of BMI in the association between SSB intake and 25(OH)D. A total of 4505 representative U.S. adults aged above 20 years and without liver conditions were selected from the 2013–2014 NHANES. All analyses were performed under survey modules with appropriate sampling weights. The prevalence of 25(OH)D insufficiency and deficiency was 37.8% and 24.1% in U.S. adults, respectively. Compared with non-SSB consumers, an …
Tumor Microenvironment As A Therapeutic Target In Melanoma Treatment, Naji Kharouf, Thomas W. Flanagan, Sofie Yasmin Hassan, Hosam Shalaby, Marla Khabaz, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan
Tumor Microenvironment As A Therapeutic Target In Melanoma Treatment, Naji Kharouf, Thomas W. Flanagan, Sofie Yasmin Hassan, Hosam Shalaby, Marla Khabaz, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan
School of Graduate Studies Faculty Publications
The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. Accumulated evidence indicates that the maintenance and progression of tumor cells is determined by components of the microenvironment, which include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). As a solid tumor, melanoma is not only a tumor mass of monolithic …
An Aerobic Exercise Intervention To Improve Metabolic Health Among People Living With Hiv With At-Risk Alcohol Use: The Alive-Ex Research Study Protocol, Liz Simon, Stefany D. Primeaux, Danielle E. Levitt, Brianna Bourgeois, Neil M. Johannsen, Adrianna Peters, Jameel Ahmed, Richard H. Marshall, Alexandra H. Fairchild, Tekeda F. Ferguson, Patricia E. Molina
An Aerobic Exercise Intervention To Improve Metabolic Health Among People Living With Hiv With At-Risk Alcohol Use: The Alive-Ex Research Study Protocol, Liz Simon, Stefany D. Primeaux, Danielle E. Levitt, Brianna Bourgeois, Neil M. Johannsen, Adrianna Peters, Jameel Ahmed, Richard H. Marshall, Alexandra H. Fairchild, Tekeda F. Ferguson, Patricia E. Molina
School of Medicine Faculty Publications
Background: Effective antiretroviral therapy (ART) in people living with HIV (PLWH) has improved life expectancy and increased risk of age-associated cardiometabolic comorbidities. At-risk alcohol use is more frequent among PLWH and increases the risk of health challenges. PLWH with at-risk alcohol use are more likely to meet criteria for prediabetes/diabetes and this is associated with impaired whole-body glucose-insulin dynamics. Methods: The Alcohol & Metabolic Comorbidities in PLWH: Evidence Driven Interventions Study (ALIVE-Ex Study, NCT03299205) is a longitudinal, prospective, interventional study to determine the effects of an aerobic exercise protocol on improving dysglycemia among PLWH with at-risk alcohol use. The intervention …
Mitochondrial Dysfunction: At The Nexus Between Alcohol-Associated Immunometabolic Dysregulation And Tissue Injury, Robert W. Siggins, Patrick M. Mcternan, Liz Simon, Flavia M. Souza-Smith, Patricia E. Molina
Mitochondrial Dysfunction: At The Nexus Between Alcohol-Associated Immunometabolic Dysregulation And Tissue Injury, Robert W. Siggins, Patrick M. Mcternan, Liz Simon, Flavia M. Souza-Smith, Patricia E. Molina
School of Medicine Faculty Publications
Alcohol misuse, directly or indirectly as a result of its metabolism, negatively impacts most tissues, including four with critical roles in energy metabolism regulation: the liver, pancreas, adipose, and skeletal muscle. Mitochondria have long been studied for their biosynthetic roles, such as ATP synthesis and initiation of apoptosis. However, current research has provided evidence that mitochondria participate in myriad cellular processes, including immune activation, nutrient sensing in pancreatic β-cells, and skeletal muscle stem and progenitor cell differentiation. The literature indicates that alcohol impairs mitochondrial respiratory capacity, promoting reactive oxygen species (ROS) generation and disrupting mitochondrial dynamics, leading to dysfunctional mitochondria …