Internal Medicine Commons^™

The Gastrointestinal-Brain-Microbiota Axis: A Promising Therapeutic Target For Ischemic Stroke, Yan-Hao Wei, Ren-Tang Bi, Yan-Mei Qiu, Chun-Lin Zhang, Jian-Zhuang Li, Ya-Nan Li, Bo Hu

Faculty, Staff and Student Publications

Ischemic stroke is a highly complex systemic disease characterized by intricate interactions between the brain and gastrointestinal tract. While our current understanding of these interactions primarily stems from experimental models, their relevance to human stroke outcomes is of considerable interest. After stroke, bidirectional communication between the brain and gastrointestinal tract initiates changes in the gastrointestinal microenvironment. These changes involve the activation of gastrointestinal immunity, disruption of the gastrointestinal barrier, and alterations in gastrointestinal microbiota. Importantly, experimental evidence suggests that these alterations facilitate the migration of gastrointestinal immune cells and cytokines across the damaged blood-brain barrier, ultimately infiltrating the ischemic brain. …

Ccl4 Regulates Eosinophil Activation In Eosiccl4 Regulates Eosinophil Activation In Eosinophilic Airway Inflammationnophilic Airway Inflammation, Hanh Hong Chu, Yoshiki Kobayashi, Dan Van Bui, Yasutaka Yun, Linh Manh Nguyen, Akitoshi Mitani, Kensuke Suzuki, Mikiya Asako, Akira Kanda, Hiroshi Iwai

Faculty, Staff and Student Publications

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory airway disease accompanied by eosinophilic inflammation, the mechanisms of which are unknown. We recently found that CCL4/MIP-1β-a specific ligand for CCR5 receptors-was implicated in eosinophil recruitment into the inflammatory site and was substantially released from activated eosinophils. Moreover, it was found in nasal polyps from patients with ECRS, primarily in epithelial cells. In the present study, the role of epithelial cell-derived CCL4 in eosinophil activation was investigated. First, CCL4 expression in nasal polyps from patients with ECRS as well as its role of CCL4 in eosinophilic airway inflammation were investigated in an in …

Association Between Abnormal Lipid Profile And Inflammation And Progression Of Myelodysplastic Syndrome To Acute Leukemia, Wei Qiao, Elliana Young, Chun Feng, Suyu Liu, Jeff Jin, Laila Noor, Cristhiam M Rojas Hernandez, Gautam Borthakur, Olga Gorlova, Vahid Afshar-Kharghan

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with a small risk of developing hematologic malignancies and a higher risk of cardiovascular diseases (CVD). We asked whether the reverse correlation exists and cardiometabolic risk factors have an impact on the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML). We investigated the association between abnormal lipid profiles and inflammation in MDS, which shares many genetic mutations with CHIP, and the risk of developing acute leukemia. We examined the medical records of 11071 MDS patients. Among them, 5422 had at least one lipid profile or C-reactive protein (CRP) measurement. In …

Targeting Hyaluronic Acid Synthase-3 (Has3) For The Treatment Of Advanced Renal Cell Carcinoma, Xiaohan Xu, Kyle L Poulsen, Lijuan Wu, Shan Liu, Tatsunori Miyata, Qiaoling Song, Qingda Wei, Chenyang Zhao, Chunhua Lin, Jinbo Yang

Faculty, Staff and Student Publications

Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a …

Adipocyte-Derived Serum Amyloid A Promotes Angiotensin Ii–Induced Abdominal Aortic Aneurysms In Obese C57bl/6j Mice, Preetha Shridas, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Steve W. Leung, Adam J. Dugan, Sean E. Thatcher, Lisa A. Cassis, Frederick C. De Beer, Nancy R. Webb, Lisa R. Tannock

Internal Medicine Faculty Publications

Background: Obesity increases the risk for human abdominal aortic aneurysms (AAAs) and enhances Ang II (angiotensin II)-induced AAA formation in C57BL/6J mice. Obesity is also associated with increases in perivascular fat that expresses proinflammatory markers including SAA (serum amyloid A). We previously reported that deficiency of SAA significantly reduces Ang II-induced inflammation and AAA in hyperlipidemic apoE-deficient mice. In this study. we investigated whether adipose tissue-derived SAA plays a role in Ang II-induced AAA in obese C57BL/6J mice.

Methods: The development of AAA was compared between male C57BL/6J mice (wild type), C57BL/6J mice lacking SAA1.1, SAA2.1, and SAA3 …

Contrast-Induced Encephalopathy Following Diagnostic Coronary Angiography, Hytham Rashid, Andrew Good, Jonathan Brown, Tusharkumar Pansuriya, Alan Fisher Covin, Mir Ali Sadat

Gulf Coast Division GME Research Day 2022

No abstract provided.

Pulmonary Inflammation And Injury Triggered By Spine Surgery In Recovered Covid-19 Patients Demand Consideration, Luciano Rodrigo Lopes, Silvana Kertzer Kasinski

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Intravesical Cd74 And Cxcr4, Macrophage Migration Inhibitory Factor (Mif) Receptors, Mediate Bladder Pain, Shaojing Ye, Fei Ma, Dlovan F. D. Mahmood, Katherine L. Meyer-Siegler, Raymond E. Menard, David E. Hunt, Lin Leng, Richard Bucala, Pedro L. Vera

Physiology Faculty Publications

BACKGROUND: Activation of intravesical protease activated receptor 4 (PAR4) leads to release of urothelial macrophage migration inhibitory factor (MIF). MIF then binds to urothelial MIF receptors to release urothelial high mobility group box-1 (HMGB1) and elicit bladder hyperalgesia. Since MIF binds to multiple receptors, we investigated the contribution of individual urothelial MIF receptors to PAR4-induced HMGB1 release in vivo and in vitro and bladder pain in vivo.

METHODOLOGY/PRINCIPAL FINDINGS: We tested the effect of intravesical pre-treatment with individual MIF or MIF receptor (CD74, CXCR4, CXCR2) antagonists on PAR4-induced HMGB1 release in vivo (female C57/BL6 mice) and in vitro (primary …

A Distinct Difference Between Air And Mucosal Temperatures In Human Respiratory Tract, Mehdi Khosravi, Ruei-Lung Lin, Ashish P. Maskey, Subodh Pandey, An-Hsuan Lin, Lu-Yuan Lee

Internal Medicine Faculty Publications

xtensive evidence indicates that several types of temperature-sensitive ion channels are abundantly expressed in the sensory nerves innervating airway mucosa. Indeed, airway temperature is known to play an important role in regulating respiratory functions. However, the actual airway mucosal temperature and its dynamic changes during the respiratory cycle have not been directly measured. In previous studies, airway tissue temperature was often estimated by indirect measurement of the peak exhaled breath temperature (PEBT). In view of the poor thermal conductivity of air, we believe that the airway tissue temperature cannot be accurately determined by the exhaled air temperature, and this study …

Can Charcoal Improve Outcomes In Covid-19 Infections?, Zeid J. Khitan, Imran Khawaja, Maurice A. Mufson, Juan R. Sanabria, Nader G. Abraham, Stephen J. Peterson, Uma Sundaram, Joseph I. Shapiro

Internal Medicine

COVID-19 infection causes considerable morbidity and mortality, especially to those who are aged, have impaired renal function and are obese. We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation.

Canakinumab To Reduce Deterioration Of Cardiac And Respiratory Function In Sars-Cov-2 Associated Myocardial Injury With Heightened Inflammation (Canakinumab In Covid-19 Cardiac Injury: The Three C Study), Calvin C Sheng, Debasis Sahoo, Siddharth Dugar, Robier Aguillon Prada, Tom Kai Ming Wang, Ossama K Abou Hassan, Danielle Brennan, Daniel A Culver, Prabalini Rajendram, Abhijit Duggal, A Michael Lincoff, Steven E Nissen, Venu Menon, Paul C Cremer

Faculty, Staff and Student Publications

BACKGROUND: In patients with Covid-19, myocardial injury and increased inflammation are associated with morbidity and mortality. We designed a proof-of-concept randomized controlled trial to evaluate whether treatment with canakinumab prevents progressive respiratory failure and worsening cardiac dysfunction in patients with SARS-CoV2 infection, myocardial injury, and high levels of inflammation.

HYPOTHESIS: The primary hypothesis is that canakiumab will shorten time to recovery.

METHODS: The three C study (canakinumab in Covid-19 Cardiac Injury, NCT04365153) is a double-blind, randomized controlled trial comparing canakinumab 300 mg IV, 600 mg IV, or placebo in a 1:1:1 ratio in hospitalized Covid-19 patients with elevations in troponin …

Loss Of Uncoupling Protein 3 Attenuates Western Diet-Induced Obesity, Systemic Inflammation, And Insulin Resistance In Rats, Tyler M Lomax, Sadia Ashraf, Gizem Yilmaz, Romain Harmancey

Faculty, Staff and Student Publications

OBJECTIVE: Uncoupling protein 3 (UCP3) is a mitochondrial carrier related to fatty acid metabolism. Although gene variants of UCP3 are associated with human obesity, their contribution to increased adiposity remains unclear. This study investigated the impact that loss of UCP3 has on diet-induced obesity in rats.

METHODS: Male UCP3 knockout rats (ucp3

RESULTS: Loss of UCP3 decreased fat mass gain, white adipocytes size, and systemic inflammation. The ucp3

CONCLUSIONS: Loss of UCP3 partially protects rats from diet-induced obesity. This phenotype is related to induction of a compensatory antioxidant mechanism and prevention of iBAT whitening.

Role Of Micro-Rna For Pain After Surgery: Narrative Review Of Animal And Human Studies, Juan P Cata, Aysegul Gorur, Xiaoyi Yuan, Nathaniel K Berg, Anil K Sood, Holger K Eltzschig

Faculty, Staff and Student Publications

One of the most prevalent symptoms after major surgery is pain. When postoperative pain treatment is unsatisfactory, it can lead to poor surgical recovery, decreased quality of life, and increased health care costs. Current analgesics, single or in combination, have limited efficacy due to low potency, limited duration of action, toxicities, and risk of addiction. The lack of nonaddictive strong analgesics along with the over prescription of opioids has led to an opioid epidemic in the United States. Therefore, there is an urgent need for the development of newer analgesics. Microribonucleic acids (miRNAs) are small noncoding RNA molecules that modulate …

The Elevated Systemic Cytokine Levels In Hiv Patients Are Not Associated With An Elevated Pulmonary Cytokine Environment., Rafael Fernandez-Botran, Andrea Reyes-Vega, Yasmany García, Chanakya Charan Tirumala, Praneet Kumar Srisailam, Anupama Raghuram, Paula Peyrani, Stephen P. Furmanek, Mahder A. Tella, Jeffrey D. Ritzenthaler, Jesse Roman, Julio A. Ramirez

Faculty and Staff Scholarship

Background

HIV-positive patients on anti-retroviral therapy (ART) are at higher risk of developing many non-AIDS related chronic diseases, including chronic obstructive pulmonary disease (COPD), compared to HIV-negative individuals. While the mechanisms are not clear, a persistent pro-inflammatory state appears to be a key contributing factor. The aims of this study were to investigate whether HIV-positive patients without COPD present evidence of potentially predisposing abnormal pulmonary cytokine/chemokine environment and to explore the relationship between pulmonary and systemic cytokine levels.

Methods

This study included 39 HIV-seropositive and 34 HIV-seronegative subjects without COPD. All were subjected to outpatient bronchoscopy with bronchoalveolar lavage fluid …

Adenosine At The Interphase Of Hypoxia And Inflammation In Lung Injury, Xiangyun Li, Nathanial K Berg, Tingting Mills, Kaiying Zhang, Holger K Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

Hypoxia and inflammation often coincide in pathogenic conditions such as acute respiratory distress syndrome (ARDS) and chronic lung diseases, which are significant contributors to morbidity and mortality for the general population. For example, the recent global outbreak of Coronavirus disease 2019 (COVID-19) has placed viral infection-induced ARDS under the spotlight. Moreover, chronic lung disease ranks the third leading cause of death in the United States. Hypoxia signaling plays a diverse role in both acute and chronic lung inflammation, which could partially be explained by the divergent function of downstream target pathways such as adenosine signaling. Particularly, hypoxia signaling activates adenosine …

Utilization Of Imaging To Identify A Benign Condition Mimicking Acute Appendicitis In A Child, Neelam Phalke Md, Zubin Mehta Md, Samrat Das Md

School of Medicine Faculty Research

One of the most concerning causes of abdominal pain affecting children is acute appendicitis. However, there are benign conditions that can closely mimic appendicitis in children. In this article, we present a case of a child admitted for possible acute appendicitis and determined to have a condition known as omental infarction. The patient was managed medically and made a full recovery without surgical intervention. The aim of this case report is to review omental infarction and present a way of differentiating this disease from appendicitis, utilizing imaging, with the goal of avoiding surgical intervention. We also discuss the presentation and …

Sclerosing Mesenteritis: Clinical Presentation, Imaging Findings, And Treatment, Jennifer Nauheim, Bsc, Rose Onyeali, Md

The Medicine Forum

CASE PRESENTATION

A 67-year old male with a history of myocardial infarction status post percutaneous coronary intervention and stage IV bladder cancer status post radical cystoprostatectomy with ileal neobladder reconstruction and chemotherapy (cisplatin and gemcitabine) presented with progressive, severe epigastric and lower abdominal pain associated with nausea. The pain had intensified over the previous week and was associated with a recent fifteen pound weight loss in the setting of poor oral intake. He denied nausea or diarrhea. His physical exam was notable for abdominal tympany and tenderness. His labs were notable for mild hyperkalemia (potassium 5.0 mmol/L), normal white blood …

A Case Of Secondary Hemophagocytic Lymphohistiocytosis In An Adult Patient Treated With Concurrent Dexamethasone And Interleukin-1 Receptor Blockade, Vikas Sunder, Md

The Medicine Forum

INTRODUCTION

Hemophagocytic Lymphohistiocytosis (HLH) is a rare, life-threatening syndrome of overwhelming inflammation caused by activation and proliferation of T-lymphocytes and hemophagocytic macrophages. This uncontrolled proliferation of macrophages creates a cytokine storm with resultant tissue damage. HLH is associated with clinical and laboratory findings which include fever, cytopenias, hepatic dysfunction, splenomegaly, and marked hyperferritinemia.1-3 There exists limited epidemiologic data on adult (age ≥ 18 years) cases of HLH, and its incidence is uncertain. HLH can be due to inherited mutations causing immune system dysregulation or secondary to underlying malignancy, infection, or rheumatologic condition. Macrophage activation syndrome (MAS) refers to HLH that …

Change Of Interleukin-6, C-Reactive Protein And Soluble Vascularcell Adhesion Molecule-1 Concentrations In Hemodialysispatients With Reprocessed Dialyzer, Pringgodigdo Nugroho, Aida Lydia, Marulam Mp Panggabean

Jurnal Penyakit Dalam Indonesia

Introduction. Cardiovascular disease is a major cause of morbidity and mortality in hemodialysis patients. In addition to traditional cardiovascular risk factors, non-traditional cardiovascular risk factors such as inflammation were also involved. Reprocessed dialyzer has been showed to induce less inflammation than new dialyzer, but data in diacetate cellulose membrane have not been presented. Methods. Twenty hemodialysis (HD) patients were enrolled. Pre and post study design was conducted to know post dialysis concentration changes of interleukin 6 (IL-6), C-reactive protein (CRP) and soluble vascular cell adhesion molecule-1 (sVCAM-1) at reuse 0, 5 and 10. Patients were recruited if medically stable, on …

Progenitor Cells As Remote "Bioreactors": Neuroprotection Via Modulation Of The Systemic Inflammatory Response, Peter A Walker, Phillip A Letourneau, Supinder Bedi, Shinil K Shah, Fernando Jimenez, Charles S Cox Jr

Faculty, Staff and Student Publications

Acute central nervous system (CNS) injuries such as spinal cord injury, traumatic brain injury, autoimmune encephalomyelitis, and ischemic stroke are associated with significant morbidity, mortality, and health care costs worldwide. Preliminary research has shown potential neuroprotection associated with adult tissue derived stem/progenitor cell based therapies. While initial research indicated that engraftment and transdifferentiation into neural cells could explain the observed benefit, the exact mechanism remains controversial. A second hypothesis details localized stem/progenitor cell engraftment with alteration of the loco-regional milieu; however, the limited rate of cell engraftment makes this theory less likely. There is a growing amount of preclinical data …

Hypertensive Nephropathy Treatment By Heart-Protecting Musk Pill: A Study Of Anti-Inflammatory Therapy For Target Organ Damage Of Hypertension, Dengke Tian, Shuang Ling, Gangling Chen, Yajuan Li, Jun Liu, Murad Ferid, Ka Bian

Faculty, Staff and Student Publications

This study was designed to investigate the protective effect of the heart-protecting musk pill (HMP) on inflammatory injury of kidney from spontaneously hypertensive rat (SHR). Male SHRs aged 4 weeks were divided into SHR model group, HMP low-dosage group (13.5 mg/kg), and HMP high-dosage group (40 mg/kg). Age-matched Wistar-Kyoto rats were used as normal control. All rats were killed at 12 weeks of age. Tail-cuff method and enzyme-linked immunosorbent assay were used to determine rat systolic blood pressure and angiotensin II (Ang II) contents, respectively. Renal inflammatory damage was evaluated by the following parameters: protein expressions of inflammatory cytokines, carbonyl …

Coordinated Changes In Mrna Turnover, Translation, And Rna Processing Bodies In Bronchial Epithelial Cells Following Inflammatory Stimulation, Yuxin Zhai, Zhenping Zhong, Chyi-Ying A Chen, Zhenfang Xia, Ling Song, Michael R Blackburn, Ann-Bin Shyu

Faculty, Staff and Student Publications

Bronchial epithelial cells play a pivotal role in airway inflammation, but little is known about posttranscriptional regulation of mediator gene expression during the inflammatory response in these cells. Here, we show that activation of human bronchial epithelial BEAS-2B cells by proinflammatory cytokines interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) leads to an increase in the mRNA stability of the key chemokines monocyte chemotactic protein 1 and IL-8, an elevation of the global translation rate, an increase in the levels of several proteins critical for translation, and a reduction of microRNA-mediated translational repression. Moreover, using the BEAS-2B cell system and …

Cd73-Generated Adenosine Restricts Lymphocyte Migration Into Draining Lymph Nodes, Masahide Takedachi, Dongfeng Qu, Yukihiko Ebisuno, Hiroyuki Oohara, Michelle L Joachims, Stephanie T Mcgee, Emiko Maeda, Rodger P Mcever, Toshiyuki Tanaka, Masayuki Miyasaka, Shinya Murakami, Thomas Krahn, Michael R Blackburn, Linda F Thompson

Faculty, Staff and Student Publications

After an inflammatory stimulus, lymphocyte migration into draining lymph nodes increases dramatically to facilitate the encounter of naive T cells with Ag-loaded dendritic cells. In this study, we show that CD73 (ecto-5'-nucleotidase) plays an important role in regulating this process. CD73 produces adenosine from AMP and is expressed on high endothelial venules (HEV) and subsets of lymphocytes. Cd73(-/-) mice have normal sized lymphoid organs in the steady state, but approximately 1.5-fold larger draining lymph nodes and 2.5-fold increased rates of L-selectin-dependent lymphocyte migration from the blood through HEV compared with wild-type mice 24 h after LPS administration. Migration rates of …

Role Of A2b Adenosine Receptor Signaling In Adenosine-Dependent Pulmonary Inflammation And Injury, Chun-Xiao Sun, Hongyan Zhong, Amir Mohsenin, Eva Morschl, Janci L Chunn, Jose G Molina, Luiz Belardinelli, Dewan Zeng, Michael R Blackburn

Faculty, Staff and Student Publications

Adenosine has been implicated in the pathogenesis of chronic lung diseases such as asthma and chronic obstructive pulmonary disease. In vitro studies suggest that activation of the A2B adenosine receptor (A2BAR) results in proinflammatory and profibrotic effects relevant to the progression of lung diseases; however, in vivo data supporting these observations are lacking. Adenosine deaminase-deficient (ADA-deficient) mice develop pulmonary inflammation and injury that are dependent on increased lung adenosine levels. To investigate the role of the A2BAR in vivo, ADA-deficient mice were treated with the selective A2BAR antagonist CVT-6883, and pulmonary inflammation, fibrosis, and airspace integrity were assessed. Untreated and …