Medical Pharmacology Commons^™

Pharmacologic Interventions To Reduce Cardiopulmonary Bypass Induced Inflammation In Cardiac Surgery: A Scoping Review, Wyatt Anderson

Student Works

ABSTRACT

1. Structured summary

Background

Cardiopulmonary bypass (CPB) is essential in cardiac surgery but can trigger a systemic inflammatory response that contributes to postoperative complications. The scoping review conducted has a purpose to map the existing literature on pharmacologic interventions to mitigate CPB related inflammation. While several interventions demonstrated potential anti-inflammatory effects, findings were inconsistent, and no standardized pharmacologic approach is currently agreed upon.

Methods

This scoping review followed PRISMA-ScR guidelines.Both PubMed, and CINAHL were screened for studies published between 2000 and 2024 that evaluated pharmacologic interventions aimed at reducing CPB related inflammation. After screening and duplicate removal, 10 studies met …

Maesa Ramentacea Leaf Extract Protects Against Gentamicin-Induced Nephrotoxicity In Wistar Rats By Modulating Renal Oxidative Stress, Inflammation And Apoptosis, Fahmida Akter, Md Shafiqul Islam Sovon, Baizid Hossain, Md Ariful Islam, Subrato Das, Anik Biswas, Md Sohorab Uddin, Md Mahmudul Hasan

Faculty Publications

Background: Gentamicin-induced nephrotoxicity continues to be a significant clinical concern, while effective and safe protective options remain limited. The nephroprotective potential of Maesa ramentacea has not yet been explored. To address this gap, the present study investigated the ethanolic leaf extract of M. ramentacea (MR-LEE) for its effects on gentamicin-induced kidney injury in Wistar rats. Methods: GC-MS profiling was employed to identify bioactive metabolites. Rats were categorised into five groups: control, gentamicin (100 mg/kg), gentamicin combined with silymarin (100 mg/kg), gentamicin combined with MR-LEE (200 mg/kg) and gentamicin combined with MR-LEE (400 mg/kg). Renal biomarkers, oxidative stress indicators, inflammatory and …

Anatomical Atlas Of Kinase Responsiveness To Weight Gain: Adipose Depot Reprogramming In Diet-Induced Adiposity, Wang-Hsin Lee, Zachary A. Kipp, Sally N. Pauss, Genesee J. Martinez, Mei Xu, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

Background/Objectives: Adipose tissue depots located at different anatomical sites exert differential functions in response to adiposity and glucose intolerance. These fat depots exhibit distinct metabolic signaling patterns that may influence pathological fat accumulation, thereby affecting the efficacy of anti-obesity interventions. Nonetheless, the mechanisms underpinning depot-specific signaling and pathway responsiveness remain insufficiently understood.

Methods: Kinase activity was characterized during the progression of adiposity across five adipose tissue depots in obese versus lean mice using the advanced PamGene kinome technology. Furthermore, kinase pathways in human preadipocytes and mouse 3T3-L1 preadipocytes were analyzed and compared with those in their differentiated, mature adipocytes. The …

Stim1-Dependent Treg Dysfunction Promotes Cardiometabolic Hfpef: Insights From Patients And Animal Studies, Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M. Herre, Raymond L. Benza, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Background

Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.

Methods

Circulating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 …

The Gut-Heart Axis: Exploring The Role Of The Gut Microbiome In Cardiovascular Health-A Focused Systematic Review, Yahya Makkieh, Haider Hussain Shah, Sakan Binte Imran, Shadman Mahmood Mahmood Khan Pathan, Anagha Chirayath Saju, Mounica Majooju, Aastha Garg, Tarun Naag, Rabeeul Islam, Cheeranthodika Fahima, Ramsha Ali

Electrical & Computer Engineering Faculty Publications

This focused systematic review examines the role of the gut microbiota in cardiovascular disease (CVD). The review explores mechanisms linking gut dysbiosis with CVD via microbial metabolites such as trimethylamine-Noxide (TMAO) and short-chain fatty acids (SCFAs), which affect inflammation, endothelial function, and lipid metabolism. Interventions including dietary modifications, probiotics, prebiotics, fecal microbiota transplantation, and pharmacological agents such as statins, rifaximin, and empagliflozin are evaluated for their impact on microbial composition and cardiovascular outcomes. Probiotic strains and fiber-rich diets demonstrated modest improvements in blood pressure, lipid profiles, and inflammatory markers. Studies revealed that gut microbiome alterations influence drug metabolism and bleeding …

Pioglitazone Uncouples Macrophage Inflammatory Signaling From Epithelial Oxidative Stress During Map Infection Mimicking Crohn’S Disease Treatment, Sabera Akter Bushra

Graduate Studies Theses and Dissertations 2026

Crohn’s disease (CD) is a chronic inflammatory bowel disease characterized by intestinal inflammation, epithelial barrier dysfunction, and abnormal immune signaling. CD pathophysiology is increasingly linked to Mycobacterium avium subspecies paratuberculosis (MAP) infection, which increases chronic macrophage activation and the production of inflammatory mediators that lead to epithelial damage. Among these mediators, CXCL10, TNF-α, and IL-6 contribute in inflammation, while NOX-1 and SERPINE-1 indicate epithelial oxidative stress and damage. Despite the role of macrophage-epithelial interaction in CD, selective pharmaceutical regulation of this axis remains unclear. Pioglitazone, an FDA-approved PPARγ agonist used for type 2 diabetes, is an appealing repurposing candidate, given …

Inflammatory Co-Regulation Of Voltage-Gated Sodium Channels And Na,K-Atpase In Metastatic Breast Cancer, Steven D. Scahill, Kelly Jean Sherman, Dennis Paul

School of Graduate Studies Faculty Publications

Sodium regulation is a potentially major driver of cancer metastasis. Voltage-gated sodium channels (VGSCs) and Na,K-ATPase are sodium transporters that are upregulated in many advanced carcinomas and are implicated as metastatic drivers. However, little is known about what drives this overexpression, how these proteins influence metastatic behavior, or whether these complementary sodium transporters are co-regulated in cancer. Using sodium transporter regulation in healthy neurons as a model, the present study demonstrated that the inflammatory mediator tumor necrosis factor alpha (TNFα) affects the expression of VGSCs and Na,K-ATPase in an in vitro model of metastatic breast cancer. Acute TNFα challenge increased …

Anti-Inflammatory Actions Of Trigonella Foenum-Graecum L. In Acute And Chronic Inflammation: Insights From Preclinical Studies, Angel Christella, Dzava P. F. Ismail, Eli Halimah

Pharmacology and Clinical Pharmacy Research

Chronic inflammation is a major factor in various degenerative diseases. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is often the main choice, but long-term side effects such as gastrointestinal irritation and nephrotoxicity limit their use. Therefore, natural alternatives such as Trigonella foenum-graecum (fenugreek) have attracted attention due to their bioactive compound contents with anti-inflammatory properties. This narrative review was conducted through a systematic search of articles from the last 10 years in PubMed and Scopus. Keywords used a combination of MeSH and free terms related to fenugreek and anti-inflammatory agents. In vitro and in vivo studies evaluating the anti-inflammatory effects …

Effect Of Vitamin K Supplementation On Insulin Resistance: A Review, Samantha Mccord, Rebecca Willier, Kaitlyn Kirby, Kaylin Mahoney, Lance Dillon, Rileigh Rahrig, Brianna Lu, Joshua Honaker, Emily Eddy

Pharmacy and Wellness Review

Insulin resistance is one of the pathological hallmarks that leads to the development of type II diabetes mellitus (T2DM). Around 40% of people aged 18 to 44 living in the United States have insulin resistance. Recent research, coupled with a better understanding of how vitamin K functions in the body, suggests that this vitamin could potentially help reduce insulin resistance. Vitamin K is not included in the American Diabetes Association (ADA) guidelines for the treatment of insulin resistance, but it has been shown to have some benefits in patients with T2DM. It may also serve as a treatment option for …

Effects Of Interleukin-22 (Il-22) On Necroptosis, Inflammatory Responses, And Metabolism Of Mycobacterium Tuberculosis Stimulated Type 2 Diabetes Mellitus Mouse Macrophages, Bismark Owusu-Afriyie

Biotechnology Theses

Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and causes nearly 1.3 million deaths per year. Limited information is available about the immune responses during Mtb infection in type 2 diabetic hosts. Our laboratory developed an experimentally induced type 2 diabetes (T2DM) model in wild-type C57BL/6 mice and found that IL-22 and type 3 innate lymphoid cells (ILC3s) reduce inflammation and mortality of Mtb-infected T2DM mice. Our laboratory also found that Mtb-infected alveolar macrophages (AMs) from T2DM mice undergo necroptosis compared to Mtb-infected AMs of non-T2DM mice. In the current study, we determined whether …

A Novel Sorbicillinoid Compound As A Potent Anti‐Inflammation Agent Through Inducing Nlrp3 Protein Degradation, Fangfang Wang, Youwei Zhang

Faculty Scholarship

Background and Purpose: Chronic inflammation is pathogenic and contributes to human diseases, causing a significant threat to public health. The NLR family pyrin domain‐containing protein 3 (NLRP3) is the best‐characterized factor regulating inflammation. Therefore, targeting NLRP3 has the potential to treat inflammatory diseases and improve human health. Experimental Approach: Lipopolysaccharide was used to induce inflammation in cell cultures. Lipopolysaccharide/d‐galactosamine and dextran sulfate sodium salt were used to induce acute liver inflammation and ulcerative colitis respectively in C57BL/6J mice. Western blotting, immunofluorescence, immunoprecipitation, quantitative PCR and enzyme‐linked immunosorbent assay (ELISA) were used to evaluate the activation of the inflammatory response in …

Combination Sodium Nitrite And Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity In A “2-Hit” Murine Model, Kyle B. Lapenna, Zhen Li, Jake E. Doiron, Thomas E. Sharp, Huijing Xia, Karl Moles, Kashyap Koul, John S. Wang, David J. Polhemus, Traci T. Goodchild, Ravi B. Patel, Sanjiv J. Shah, David J. Lefer

School of Medicine Faculty Publications

BACKGROUND: Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO-based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a “2-hit” murine model. METHODS AND RESULTS: Nine-week-old male C57BL/6 N mice (n=15 per group) were treated concurrently with high-fat …

Adipose-Specific Pparα Knockout Mice Have Increased Lipogenesis By Pask–Srebp1 Signaling And A Polarity Shift To Inflammatory Macrophages In White Adipose Tissue, Terry D. Hinds, Jr., Zachary A. Kipp, Mei Xu, Frederique B. Yiannikouris, Andrew J. Morris, Donald F. Stec, Walter Wahli, David E. Stec

Pharmacology and Nutritional Sciences Faculty Publications

The nuclear receptor PPARα is associated with reducing adiposity, especially in the liver, where it transactivates genes for β-oxidation. Contrarily, the function of PPARα in extrahepatic tissues is less known. Therefore, we established the first adipose-specific PPARα knockout (Ppara^FatKO) mice to determine the signaling position of PPARα in adipose tissue expansion that occurs during the development of obesity. To assess the function of PPARα in adiposity, female and male mice were placed on a high-fat diet (HFD) or normal chow for 30 weeks. Only the male Ppara^FatKO animals had significantly more adiposity in the inguinal white …

Novel Insights Into The Anti-Diabetic Mechanism(S) Of Withania Coagulans And Its Active Constituent, Coagulansin-A, Mariyam Khalid Naeem

Dissertations

Type 2 diabetes mellitus has become a serious medical challenge of the 21st century with a dramatic surge in diabetes cases since the last decade. It accounts for 90-95% of all cases of diabetes mellitus. The interplay between insulin resistance and beta cells dysfunction plays a crucial role in the pathophysiology of diabetes mellitus. Type 2 diabetes mellitus is characterized by peripheral insulin resistance in skeletal muscles that leads to a constellation of metabolic disorders, and exhaustion of pancreatic beta cells to maintain euglycemia. The inability of pancreatic beta cells to compensate insulin demand in an insulin-resistant state, result in …

High-Density Lipoproteins And Serum Amyloid A (Saa), Nancy R. Webb

Pharmacology and Nutritional Sciences Faculty Publications

PURPOSE OF REVIEW: Serum amyloid A (SAA) is a highly sensitive acute phase reactant that has been linked to a number of chronic inflammatory diseases. During a systemic inflammatory response, liver-derived SAA is primarily found on high-density lipoprotein (HDL). The purpose of this review is to discuss recent literature addressing the pathophysiological functions of SAA and the significance of its association with HDL.

RECENT FINDINGS: Studies in gene-targeted mice establish that SAA contributes to atherosclerosis and some metastatic cancers. Accumulating evidence indicates that the lipidation state of SAA profoundly affects its bioactivities, with lipid-poor, but not HDL-associated, SAA capable of …

Natural Product Heme Oxygenase Inducers As Treatment For Nonalcoholic Fatty Liver Disease, David E. Stec, Terry D. Hinds Jr.

Pharmacology and Nutritional Sciences Faculty Publications

Heme oxygenase (HO) is a critical component of the defense mechanism to a wide variety of cellular stressors. HO induction affords cellular protection through the breakdown of toxic heme into metabolites, helping preserve cellular integrity. Nonalcoholic fatty liver disease (NAFLD) is a pathological condition by which the liver accumulates fat. The incidence of NAFLD has reached all-time high levels driven primarily by the obesity epidemic. NALFD can progress to nonalcoholic steatohepatitis (NASH), advancing further to liver cirrhosis or cancer. NAFLD is also a contributing factor to cardiovascular and metabolic diseases. There are currently no drugs to specifically treat NAFLD, with …

Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Pharmacology and Nutritional Sciences Faculty Publications

Circulating fatty acids (FAs) increase with obesity and can drive mitochondrial damage and inflammation. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial protein that positively regulates nicotinamide adenine dinucleotide phosphate (NADPH), a key mediator of energy transduction and redox homeostasis. The role that NNT-regulated bioenergetics play in the inflammatory response of immune cells in obesity is untested. Our objective was to determine how free fatty acids (FFAs) regulate inflammation through impacts on mitochondria and redox homeostasis of peripheral blood mononuclear cells (PBMCs). PBMCs from lean subjects were activated with a T cell-specific stimulus in the presence or absence of generally pro-inflammatory …

The Guanylate Cyclase C-Cgmp Signaling Axis Opposes Intestinal Epithelial Injury And Neoplasia., Jeffrey A. Rappaport, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Guanylate cyclase C (GUCY2C) is a transmembrane receptor expressed on the luminal aspect of the intestinal epithelium. Its ligands include bacterial heat-stable enterotoxins responsible for traveler's diarrhea, the endogenous peptide hormones uroguanylin and guanylin, and the synthetic agents, linaclotide, plecanatide, and dolcanatide. Ligand-activated GUCY2C catalyzes the synthesis of intracellular cyclic GMP (cGMP), initiating signaling cascades underlying homeostasis of the intestinal epithelium. Mouse models of GUCY2C ablation, and recently, human populations harboring GUCY2C mutations, have revealed the diverse contributions of this signaling axis to epithelial health, including regulating fluid secretion, microbiome composition, intestinal barrier integrity, epithelial renewal, cell cycle progression, responses …

Minocycline Protects Developing Brain Against Ethanol-Induced Damage, Xin Wang, Kai Zhang, Fanmuyi Yang, Zhenhua Ren, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are caused by ethanol exposure during the pregnancy and is the leading cause of mental retardation. Ethanol exposure during the development results in the loss of neurons in the developing brain, which may underlie many neurobehavioral deficits associated with FASD. It is important to understand the mechanisms underlying ethanol-induced neuronal loss and develop appropriate therapeutic strategies. One of the potential mechanisms involves neuroimmune activation. Using a third trimester equivalent mouse model of ethanol exposure, we demonstrated that ethanol induced a wide-spread neuroapoptosis, microglial activation, and neuroinflammation in C57BL/6 mice. Minocycline is an antibiotic that inhibits …

Pathologic Evaluation Of Tumor-Associated Macrophage Density And Vessel Inflammation In Invasive Breast Carcinomas, Yoshihiro Morita, Roy Zhang, Macall Leslie, Smita Adhikari, Nafis Hasan, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumor-associated macrophages (TAMs) are major constituents of the tumor microenvironment in solid tumors and have been implicated as mediators of tumor progression, invasion and metastasis. Correspondingly, accumulation of TAMs is associated with unfavorable clinical outcomes in numerous types of solid tumors. E-selectin is a hallmark of inflammation and a key adhesion molecule that accommodates the initial contact of circulating immune cells with the inflamed vessel surface. Currently, the association between E-selectin and TAMs is not fully elucidated; therefore, the present study investigated the association between vessel inflammation, TAM infiltration, and clinical outcome in breast cancer. A total of 53 procedure-naïve …

Induction Of Mir-155 After Brain Injury Promotes Type 1 Interferon And Has A Neuroprotective Effect., Emily Harrison, Kathleen M. Emanuel, Benjamin G. Lamberty, Brenda M. Morsey, Min Li, Matthew L. Kelso, Sowmya V. Yelamanchili, Howard S. Fox

Journal Articles: Pharmacology & Experimental Neuroscience

Traumatic brain injury (TBI) produces profound and lasting neuroinflammation that has both beneficial and detrimental effects. Recent evidence has implicated microRNAs (miRNAs) in the regulation of inflammation both in the periphery and the CNS. We examined the expression of inflammation associated miRNAs in the context of TBI using a mouse controlled cortical impact (CCI) model and found increased levels of miR-21, miR-223 and miR-155 in the hippocampus after CCI. The expression of miR-155 was elevated 9-fold after CCI, an increase confirmed by in situ hybridization (ISH). Interestingly, expression of miR-155 was largely found in neuronal nuclei as evidenced by co-localization …

Hypersensitivity Of Vagal Pulmonary Afferents Induced By Tumor Necrosis Factor Alpha In Mice, Ruei-Lung Lin, Qihai Gu, Lu-Yuan Lee

Physiology Faculty Publications

Tumor necrosis factor alpha (TNFα), a pro-inflammatory cytokine, plays a significant role in the pathogenesis of allergic asthma. Inhalation of TNFα also induces airway hyperresponsiveness in healthy human subjects, and the underlying mechanism is not fully understood. A recent study reported that TNFα caused airway inflammation and a sustained elevation of pulmonary chemoreflex responses in mice, suggesting a possible involvement of heightened sensitivity of vagal pulmonary C-fibers. To investigate this possibility, the present study aimed to investigate the effect of a pretreatment with TNFα on the sensitivity of vagal pulmonary afferents in anesthetized mice. After TNFα (10 μg/ml, 0.03 ml) …

Mammary Epithelial Polarity And Macrophage Infiltration, Ren Xu

Pharmacology and Nutritional Sciences Faculty Publications

Loss of epithelial cell polarity and inflammation are hallmarks of breast cancer development. Although the association between the disruption of tissue polarity and inflammation has been demonstrated, we know little about how these two events are coupled. Using the 3D co-culture model of mammary epithelial cells and monocytes, a recent study reveals a link between disruption of epithelial polarity and monocytes infiltration.

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Effect Of Genipin On Cisplatin- Induced Nephrotoxicity, Eglal Orner Mahgoub

Theses

Cisplatin (CSP) is a potent and widely used chemotherapeutic agent. However, clinical efficacy of CSP is compromised due to the elicitation of nephrotoxicity and ototoxicity. In this study, I have investigated the nephroprotective effects of a phytochemical – genipin (GP) isolated from gardenia flower (Gardenia jasminoides), on a murine model of cisplatin-induced nephropathy. CSP-induced renal tissue injury was characterized by elevated levels of serum blood urea nitrogen (BUN), creatinine (Cr) and cystatin-C. In addition, levels of kidney injury molecule-1 (KIM-1) were increased in the renal tissues of CSP administered animals. CSP also induced renal oxidative stress, evidenced by increased NADPH …

Binge Ethanol Exposure Causes Endoplasmic Reticulum Stress, Oxidative Stress And Tissue Injury In The Pancreas, Zhenhua Ren, Xin Wang, Mei Xu, Fanmuyi Yang, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Alcohol abuse is associated with both acute and chronic pancreatitis. Repeated episodes of acute pancreatitis or pancreatic injury may result in chronic pancreatitis. We investigated ethanol-induced pancreatic injury using a mouse model of binge ethanol exposure. Male C57BL/6 mice were exposed to ethanol intragastrically (5 g/kg, 25% ethanol w/v) daily for 10 days. Binge ethanol exposure caused pathological changes in pancreas demonstrated by tissue edema, acinar atrophy and moderate fibrosis. Ethanol caused both apoptotic and necrotic cell death which was demonstrated by the increase in active caspase-3, caspase-8, cleaved PARP, cleaved CK-18 and the secretion of high mobility group protein …

Resveratrol Supplementation Confers Neuroprotection In Cortical Brain Tissue Of Nonhuman Primates Fed A High-Fat/Sucrose Diet, Michel Bernier, Devin Wahl, Ahmed Ali, Joanne Allard, Shakeela Faulkner, Artur Wnorowski, Mitesh Sanghvi, Ruin Moaddel, Irene Alfaras, Julie A. Mattison, Stefano Tarantini, Zsuzsanna Tucsek, Zoltan Ungvari, Anna Csiszar, Kevin J. Pearson, Rafael De Cabo

Pharmacology and Nutritional Sciences Faculty Publications

Previous studies have shown positive effects of long-term resveratrol (RSV) supplementation in preventing pancreatic beta cell dysfunction, arterial stiffening and metabolic decline induced by high-fat/high-sugar (HFS) diet in nonhuman primates. Here, the analysis was extended to examine whether RSV may reduce dietary stress toxicity in the cerebral cortex of the same cohort of treated animals. Middle-aged male rhesus monkeys were fed for 2 years with HFS alone or combined with RSV, after which whole-genome microarray analysis of cerebral cortex tissue was carried out along with ELISA, immunofluorescence, and biochemical analyses to examine markers of vascular health and inflammation in the …

Neuroinflammation And Neurologic Deficits In Diabetes Linked To Brain Accumulation Of Amylin, Sarah Srodulski, Savita Sharma, Adam B. Bachstetter, Jennifer M. Brelsfoard, Conrado Pascual, Xinmin Simon Xie, Kathryn E. Saatman, Linda J. Van Eldik, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: We recently found that brain tissue from patients with type-2 diabetes (T2D) and cognitive impairment contains deposits of amylin, an amyloidogenic hormone synthesized and co-secreted with insulin by pancreatic β-cells. Amylin deposition is promoted by chronic hypersecretion of amylin (hyperamylinemia), which is common in humans with obesity or pre-diabetic insulin resistance. Human amylin oligomerizes quickly when oversecreted, which is toxic, induces inflammation in pancreatic islets and contributes to the development of T2D. Here, we tested the hypothesis that accumulation of oligomerized amylin affects brain function.

METHODS: In contrast to amylin from humans, rodent amylin is neither amyloidogenic nor cytotoxic. …

The Role Of Nitric Oxide Dysregulation In Tumor Maintenance, Christopher Rabender

Theses and Dissertations

The inflammatory nature of the tumor microenvironment provides a cytokine and chemokine rich proliferative environment. Much of the responsibility of this environment is due to the production of Reactive Oxygen Species (ROS). These studies examined the proliferative rich tumor environment from a new perspective of Nitric Oxide Synthase (NOS) dysregulation. NOS’s have the ability to become uncoupled and generate superoxide in lieu of nitric oxide (NO). A requirement of NOS for the production of NO is the cofactor tetrahydrobiopterin (BH4) and when it is missing NOS becomes uncoupled and turns into a peroxynitrite synthase. Here I demonstrate that NOS is …

What Is The Effectiveness Of Roxithromycin In Management Of The Signs And Symptoms Of Rheumatoid Arthritis?, Adriana Distanislao

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not roxithromycin is effective in management of the signs and symptoms of rheumatoid arthritis.

STUDY DESIGN: Review of three primary studies in the English language published in 2006, 2009, and 2011.

DATA SOURCES: Randomized, controlled and double blind clinical trials testing the effectiveness roxithromycin in management of inflammation and signs and symptoms of rheumatoid arthritis were found using the PubMed and Ovid databases.

OUTCOMES MEASURED: Improvement in the signs and symptoms of tenderness/inflammation using the American College of Rheumatology-20 (ACR-20) scoring approach, improvement of quality of …