Medical Sciences Commons^™

Rapamycin Rescues Vascular, Metabolic And Learning Deficits In Apolipoprotein E4 Transgenic Mice With Pre-Symptomatic Alzheimer’S Disease, Ai-Ling Lin, Jordan B. Jahrling, Wei Zhang, Nicholas Derosa, Vikas Bakshi, Peter Romero, Veronica Galvan, Arlan Richardson

Sanders-Brown Center on Aging Faculty Publications

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood–brain barrier integrity and glucose metabolism, compared …

Ethnic Differences In Maternal Adipokines During Normal Pregnancy, Xinhua Chen, Theresa O Scholl

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Two adipokines (adiponectin and resistin) have opposite relations with insulin resistance and inflammation. Our major focus was to determine whether there were detectable ethnic differences in maternal adipokines during pregnancy. We also explored the correlation of the adipokines with maternal glucose homeostasis, blood pressure and anthropometric parameters. Pregnant women (n = 1634) were from a large prospective cohort study in Camden NJ (African-American 36.8%; Hispanic 47.6%; Caucasian 15.6%). Serum adiponectin and resistin were measured at entry (week 16.8) and the 3rd trimester (week 30.7) using the Luminex xMapTechnology. Significant differences were observed among ethnic groups, controlling for confounding variables. African …

Tuberculosis And Cardiovascular Disease: Linking The Epidemics, Moises A. Huaman, David Henson, Eduardo Ticona, Timothy R. Sterling, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The burden of tuberculosis and cardiovascular disease (CVD) is enormous worldwide. CVD rates are rapidly increasing in low- and middle-income countries. Public health programs have been challenged with the overlapping tuberculosis and CVD epidemics. Monocyte/macrophages, lymphocytes and cytokines involved in cellular mediated immune responses against Mycobacterium tuberculosis are also main drivers of atherogenesis, suggesting a potential pathogenic role of tuberculosis in CVD via mechanisms that have been described for other pathogens that establish chronic infection and latency. Studies have shown a pro-atherogenic effect of antibody-mediated responses against mycobacterial heat shock protein-65 through cross reaction with self-antigens in human vessels. Furthermore, …

Differential Expression Of Mrna Encoding Cytokines And Chemokines In The Reproductive Tract After Infection Of Mice With Chlamydia Trachomatis, Katheryn L. Cerny, Maranda Van Fleet, Anatoly Slepenkin, Ellena M. Peterson, Phillip J. Bridges

Animal and Food Sciences Faculty Publications

Infection with Chlamydia trachomatis targets epithelial cells within the genital tract which respond by secreting chemokines and cytokines. Persistent inflammation can lead to fibrosis, tubal infertility and/or ectopic pregnancy; many infections are asymptomatic. Most studies have investigated the inflammatory response in the initial stages of infection, less is known about the later stages of infection, especially with a low, potentially asymptomatic, bacterial load. Our objective was to determine the inflammatory mediators involved in clearance of low-grade infection and the potential involvement in chronic inflammation. Six to eight week old C3H/HeJ mice were pretreated with 2.5 mg medroxyprogesterone acetate on day …

Cd36 And Na/K-Atpase- Α 1 Form A Proinflammatory Signaling Loop In Kidney, David Kennedy, Yiliang Chen, Wenxin Huang, Jamie Viterna, Jiang Liu, Kristen Westfall, Jian Tian, David Bartlett, W.H. Tang, Zijian Xie, Joseph Shapiro, Roy Silverstein

Jiang Liu

Proatherogenic, hyperlipidemic states demonstrate increases in circulating ligands for scavenger receptor CD36 (eg, oxidized low-density lipoprotein [oxLDL]) and the Na/K-ATPase (eg, cardiotonic steroids). These factors increase inflammation, oxidative stress, and progression of chronic kidney disease. We hypothesized that diet-induced obesity and hyperlipidemia potentiate a CD36/Na/K-ATPase–dependent inflammatory paracrine loop between proximal tubule cells (PTCs) and their associated macrophages and thereby facilitate development of chronic inflammation and tubulointerstitial fibrosis. ApoE^-/- and apoE^-/-/cd36^-/- mice were fed a high-fat diet for ≤32 weeks and examined for physiologic and histologic changes in renal function. Compared with apoE^-/-, apoE^{-/- …}

The Effects Of Vagus Nerve Stimulation On Neuroinflammation In Epilepsy, Elizabeth A. St. Clair, Gabriel O Albors, Pedro Irazoqui Dr., Amy Brewster

The Summer Undergraduate Research Fellowship (SURF) Symposium

Epilepsy is a neurological disorder characterized by chronic, unexplainable seizures. Recurring epileptic seizures are associated with long-term structural damage and cognitive deficits, and can even lead to sudden, unexplainable death. Approximately 30% of epilepsy cases are not responsive to medication. Epileptic seizures often induce inflammation in the brain and may increase the frequency of future seizures, resulting in a detrimental cycle. Vagus nerve stimulation (VNS) is a non-pharmaceutical treatment method for epilepsy that has been shown to reduce inflammation in peripheral pathways. The role of VNS in the modulation of neuroinflammation has yet to be demonstrated experimentally. To explore this, …

Gout, Lorrie Listebarger

Nursing Student Class Projects (Formerly MSN)

Gout is a syndrome caused by an inflammatory response creating an over production of uric acid increasing uric acid levels in the blood and body fluids. Gout is defined as a disorder resulting from tissue deposition of MSU crystals (in joints, bursae, bone, and certain other soft tissues, such as ligaments, tendons and occasionally, skin) and/or crystallization of uric acid within the renal collecting system (tubules and renal pelvis) that typically occurs in acid urine” (Terkeltaub & Edwards, 2013, p. 20). Gout is among the oldest diseases affecting approximately 3.9% of adults in America (Terkeltaub & Edwards, 2013, p. xv). …

Compensatory Fetal Membrane Mechanisms Between Biglycan And Decorin In Inflammation., Luciana Batalha De Miranda De Araujo, Casie E Horgan, Abraham Aron, Renato V. Iozzo, Beatrice E Lechner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Preterm premature rupture of fetal membranes (PPROM) is associated with infection, and is one of the most common causes of preterm birth. Abnormal expression of biglycan and decorin, two extracellular matrix proteoglycans, leads to preterm birth and aberrant fetal membrane morphology and signaling in the mouse. In humans and mice, decorin dysregulation is associated with inflammation in PPROM. We therefore investigated the link between biglycan and decorin and inflammation in fetal membranes using mouse models of intraperitoneal Escherichia coli injections superimposed on genetic biglycan and decorin deficiencies. We assessed outcomes in vivo as well as in vitro using quantitative PCR, …

Exercise Ameliorates High Fat Diet Induced Cardiac Dysfunction By Increasing Interleukin 10., Varun Kesherwani, Vishalakshi Chavali, Bryan T. Hackfort, Suresh C. Tyagi, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD) leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α) and attenuation of anti-inflammatory cytokine such as interleukin 10 (IL-10) contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, 8 week old, female C57BL/6J mice were fed with HFD and exercised (swimming …

Osteopontin: A Bridge Between Bone And The Immune System, Ellen M. Gravallese

Ellen M. Gravallese

The molecular mechanisms underlying the putative role of osteopontin in the chronic inflammatory disease rheumatoid arthritis are unclear. A study in a murine model of arthritis now demonstrates that a specific antibody directed against the exposed osteopontin epitope SLAYGLR is capable of preventing inflammatory cell infiltration in arthritic joints.

Timp3 Regulation Of Macrophage Activation And Apoptosis, Michael S. Brock

Electronic Thesis and Dissertation Repository

Acute respiratory distress syndrome (ARDS) is a lung disease involving profound inflammation. Origins of persistent inflammation in select cases of ARDS are poorly understood, and we propose persistent inflammatory macrophages may be one of its mechanisms. Macrophages polarize to either promote inflammation, or suppress inflammation. Tissue inhibitor of metalloproteinases 3 (TIMP3) reduces the pro-inflammatory polarization in macrophages. Additionally, studies have shown TIMP3 promotes apoptosis, and its absence delays recovery from bleomycin-induced lung injury.

We hypothesize that TIMP3 promotes apoptosis of murine macrophages through inhibition of metalloproteinase activity and stabilization of FAS on the cell surface. Pro-inflammatory Timp3^-/- bone marrow-derived …

Mitochondria-Associated Micrornas In Rat Hippocampus Following Traumatic Brain Injury, Wang-Xia Wang, Nishant P. Visavadiya, Jignesh D. Pandya, Peter T. Nelson, Patrick G. Sullivan, Joe E. Springer

Sanders-Brown Center on Aging Faculty Publications

Traumatic brain injury (TBI) is a major cause of death and disability. However, the molecular events contributing to the pathogenesis are not well understood. Mitochondria serve as the powerhouse of cells, respond to cellular demands and stressors, and play an essential role in cell signaling, differentiation, and survival. There is clear evidence of compromised mitochondrial function following TBI; however, the underlying mechanisms and consequences are not clear. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression post-transcriptionally, and function as important mediators of neuronal development, synaptic plasticity, and neurodegeneration. Several miRNAs show altered expression following TBI; however, the …

Systems Level Analysis Of Systemic Sclerosis Shows A Network Of Immune And Profibrotic Pathways Connected With Genetic Polymorphisms, J. Matthew Mahoney, Jaclyn Taroni, Viktor Martyanov, Tammara A. A. Wood, Casey S. Greene, Patricia A. Pioli, Monique E. Hinchcliff, Michael L. Whitfield

Dartmouth Scholarship

Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited) are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes …

Caffeic Acid Phenethyl Ester Protects Lung Alveolar Epithelial Cellsfrom Cigarette Smoke-Induced Damage, Firat Bariş Barlas, Suat Erdogan

Turkish Journal of Medical Sciences

Background/aim: To evaluate the influence of caffeic acid phenethyl ester (CAPE) on cigarette smoke (CS)-induced cell damage, oxidative stress, and inflammation in human alveolar epithelial cells. Materials and methods: A549 alveolar epithelial cells were divided into control, CS exposure, CAPE, and CS+CAPE treatment groups. Undiluted CS-exposed medium (100%) and three dilutions (50%, 25%, and 10%) of CS-exposed media were applied to cultured A549 cells, which were analyzed after 3 h of incubation. Viability was measured by MTT assay, the gene expressions were evaluated by real-time PCR, and spectrophotometric techniques were used for biochemical assessments. Results: While CS exposure markedly reduced …

Beraprost Sodium, A Prostacyclin (Pgi) Analogue, Ameliorateslipopolysaccharide-Induced Cellular Injury In Lung Alveolar Epithelial Cells, Si̇nan Vicil, Suat Erdogan

Turkish Journal of Medical Sciences

Human alveolar epithelial cells play a critical role in the pathogenesis of lung diseases. The objective of this study is to determine the contribution of beraprost sodium, a prostaglandin I_2 (PGI_2) analogue, to inflammatory and oxidative events in response to lipopolysaccharide (LPS) in airway epithelial cells. Materials and methods: Human pulmonary alveolar epithelial cells (A549) were pretreated with 10 µM beraprost sodium 30 min before stimulation with 1 µg/mL LPS for 24 h. The cellular viability assessments were evaluated by quantitative MTT test. Catalase activity and glutathione and lipid peroxidation levels were determined using spectrophotometric techniques. mRNA expression analyses were …

Neuroinflammatory Alterations Via Cd-36 In Traumatic Brain Injury, Diana G. Hernandez-Ontiveros

USF Tampa Graduate Theses and Dissertations

Traumatic brain injury (TBI) has become an increasingly unmet clinical need due to intense military conflicts worldwide. Directly impacted brain cells suffer massive death, with neighboring cells succumbing to progressive neurodegeneration accompanied by inflammatory and other secondary cell death events. Subsequent neurodegenerative events may extend to normal areas beyond the core of injury, thereby exacerbating the central nervous system’s inflammatory response to TBI. Recently CD-36 (cluster of differentiation 36/fatty acid translocase (FAT), a class B scavenger receptor of modified low-density lipoproteins (mLDLs) in macrophages, has been implicated in lipid metabolism, atherosclerosis, oxidative stress, and tissue injury in cerebral ischemia, and …

Alzheimer Disease, Inflammation, And Novel Inflammatory Marker: Resistin, Muhammet Cemal Kizilarslanoğlu, Özgür Kara, Yusuf Yeşi̇l, Mehmet Emi̇n Kuyumcu, Zeynel Abi̇di̇n Öztürk, Mustafa Cankurtaran, Samed Rahatli, Nagehan Pakaşti̇çali, Esat Çinar, Meltem Gülhan Hali̇l, Burçi̇n Şener, Eylem Şahi̇n Cankurtaran, Servet Arioğul

Turkish Journal of Medical Sciences

Background/aim: Inflammation may play an important role in Alzheimer disease (AD) pathogenesis. A growing amount of evidence indicates that resistin has hallmark regulatory functions such as inflammatory states. The aim of this study was to determine whether plasma resistin levels would be useful in the diagnosis of patients with AD and to investigate the relationships between resistin and other inflammatory markers such as hs-CRP and TNF-α. Materials and methods: In this cross-sectional study, 38 AD patients and 32 control subjects with normal cognitive function aged 65 years and over were included. The diagnosis of AD was made according to DSM-IV …

Evaluation Of Autoinflammatory Disease Genes In Nasal Polyposis, Sabri̇ Köseoğlu, Kürşat Murat Özcan, Aykut İki̇nci̇oğullari, Mehmet Ali̇ Çeti̇n, Tali̇h Özdaş, Si̇bel Özdaş, Serdar Ensari̇, Haci Hüseyi̇n Dere

Turkish Journal of Medical Sciences

To investigate cold-induced autoinflammatory syndrome 1 (CIAS1) gene polymorphisms that cause autoinflammatory diseases in patients with nasal polyposis (NP). Materials and methods: The study included 30 patients diagnosed with NP and 30 healthy age-matched individuals as a control group. CIAS1 polymorphisms were assessed by DNA sequence analysis. Patients with nasal polyps and the control group were compared in terms of gene polymorphisms. Each of the 8 polymorphisms of the CIAS1 gene was analyzed separately in the patient group. Results: The most frequently observed polymorphisms in the patient group were c.732G > A in 83%, c.663C > T in 23%, and c.1308C > A …

The Role Of C-Reactive Protein In Acute Kidney Injury, Melissa A. Pegues

All ETDs from UAB

Acute kidney injury (AKI), which manifests as an abrupt decline in renal function, occurs in ~1% of all hospitalization. Ischemia reperfusion injury (IRI), a common cause of AKI, can occur in any situation where blood flow to the kidney is significantly reduced such as hypertensive crisis, cardiovascular surgery, and inevitably during renal transplantation. Mortality from AKI is up to 80% due to incomplete knowledge of the pathogenesis of IRI and the lack of an effective therapy. It is thought that cellular damage as a result of hypoxia signals the release of proinflammatory cytokines that lead to a systemic inflammatory response. …

Tumor Necrosis Factor Alpha Converting Enzyme Inhibition During Acute Colitis In Mice: A Regional Analysis, Brian Maddox

MSU Graduate Theses

Tumor Necrosis Factor-a Converting Enzyme (TACE) induces active TNFa and may contribute to the development of colitis in humans. I hypothesized that pharmacological blockade of TNFa production would improve colitis scoring through decreased expression of inflammatory biomarkers. Acute colitis was induced in wild type BALB/c mice using 5% dextran sulfate sodium (DSS) in drinking water for 7 days. TACE inhibition was accomplished through twice daily intraperitoneal injection of DPC- 333 (10mg/kg; BSM Inc.) To determine the effects of TACE blockade during colitis, the following experimental groups (n=6-7/group) were tested: 1) vehicle; 2) DPC-333; 3) 5% DSS and vehicle; and 4) …