Diseases Commons^™

West Nile Virus And Pattern Recognition Receptors, Jordan Boswell, Verma Saguna, Phd, Chih-Yun Lai

Journal of Health Disparities Research and Practice

West Nile Virus (WNV), RNA virus is a member of the flaviviridae family that causes flu like symptoms in infected individuals, however in 1-2% cases, it causes severe neurological diseases such as encephalitis. There is no antiviral or vaccine approved so far to prevent WNV disease, therefore research to understand immune pathology is very important.

Pattern Recognition Receptors (PRR) are proteins that are expressed by cells to detect virus infection and play an important role in the innate immune system. When a PRR such as Toll-Like Receptors (TLR) and Nod-Like Receptors (NLR) detects a replicating virus, signals are sent out …

Periodontitis In Chronic Heart Failure, Hanna Fröhlich, Kristina Herrmann, Jennifer Franke, Alamara Karimi, Tobias Täger, Rita Cebola, Hugo A Katus, Christian Zugck, Lutz Frankenstein

The Texas Heart Institute Journal

Periodontal disease has been associated with an increased risk of cardiovascular events. The purpose of our study was to investigate whether a correlation between periodontitis and chronic heart failure exists, as well as the nature of the underlying cause.

We enrolled 71 patients (mean age, 54 ± 13 yr; 56 men) who had stable chronic heart failure; all underwent complete cardiologic and dental evaluations. The periodontal screening index was used to quantify the degree of periodontal disease. We compared the findings to those in the general population with use of data from the 4th German Dental Health Survey.

Gingivitis, moderate …

Hdac6 Inhibition Prevents Tnf-Α-Induced Caspase 3 Activation In Lung Endothelial Cell And Maintains Cell-Cell Junctions, Jinyan Yu, Mengshi Ma, Zhongsen Ma, Jian Fu

Center for Research on Environmental Disease Faculty Publications

Pro-inflammatory mediators such as TNF-α induce caspase activation in endothelial cells, which leads to degradation of cellular proteins, induction of apoptotic signaling, and endothelial cell dysfunction. New therapeutic agents that can inhibit caspase activation may provide protection against inflammatory injury to endothelial cells. In the present study, we examined the effects of selective histone deacetylase 6 (HDAC6) inhibition on TNF-α induced caspase 3 activation and cell-cell junction dysfunction in lung endothelial cells. We also assessed the protective effects of HDAC6 inhibition against lung inflammatory injury in a mouse model of endotoxemia. We demonstrated that selective HDAC6 inhibition or knockdown of …

The Effect Of Sleep Quality And High Intensity Physical Activity On Inflammation And Cardiovascular Disease Risk Factors In College Students, Catherine Abraham

Honors Scholar Theses

Background: Inflammation is the common denominator in chronic conditions such as obesity, diabetes, and depression. While adequate physical activity and optimal sleep quality may help maintain normal inflammation levels, evidence is somewhat conflicting. Aim: This cross-sectional observational study aimed to assess how sleep quality and high intensity physical activity associated with cardiovascular disease (CVD) risk factors and inflammatory biomarkers in a sample of young adults (n=106, ages 18-25 years). Methods: Laboratory-based assessments included lifestyle behaviors (sleep quality, Pittsburgh Sleep Quality Index; self-reported frequency/intensity of physical activity; Healthy Behavior Index derived from reported preference for diet and physical activity), CVD risk …

Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, Dominique J. Richburg

Senior Honors Theses

The intimin gene in the Locus of Enterocyte Effacement (LEE) island of pathogenicity is the primary attachment mechanism in Citrobacter rodentium. Intimin is a bacterial adhesin (protein) that attaches to obtain a niche/nutrient and thrive within the intestine. Intimin was deleted within C. rodentium to study colonization and pathogenesis in the murine intestine. Additionally, C. rodentium is an attaching/effacing pathogen, and a useful murine model in understanding Enterohemorrhagic Escherichia coli (EHEC) infection in humans. E. coli and C. rodentium cause gastroenteritis in humans and mice, respectively. C. rodentium is a murine pathogen commonly used to model gastrointestinal disease because …

Human Igg1 Antibodies Suppress Angiogenesis In A Target-Independent Manner, Sasha Bogdanovich, Younghee Kim, Takeshi Mizutani, Reo Yasuma, Laura Tudisco, Valeria Cicatiello, Ana Bastos-Carvalho, Nagaraj Kerur, Yoshio Hirano, Judit Z. Baffi, Valeria Tarallo, Shengjian Li, Tetsuhiro Yasuma, Parthasarathy Arpitha, Benjamin James Fowler, Charles B. Wright, Ivana Apicella, Adelaide Greco, Arturo Brunetti, Menotti Ruvo, Annamaria Sandomenico, Miho Nozaki, Ryo Ijima, Hiroki Kaneko, Yuichiro Ogura, Hiroko Terasaki, Balamurali K. Ambati, Jeanette H. W. Leusen, Wallace Y. Langdon, Michael R. Clark, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world’s population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type …

Why Is Postoperative Atrial Fibrillation Difficult To Prevent And Treat: Potential Roles Of Unrecognized Magnesium Deficiency And Release Of Ceramide And Platelet-Activating Factor, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Jose Luis Perez-Albela, Bella T. Altura

Touro College of Osteopathic Medicine (Middletown) Publications and Research

Heart failure is a major cause of morbidity and mortality whose costs impose staggering health-care costs and often lengthy hospitalizations. Post-operative atrial fibrillation (POAF) represents a leading cause for heart failure, particularly after cardiac and lung surgeries. Although PAOF is a common cardiac arrhythmia, it is impossible to predict. As the worldwide population is aging, the incidence and prevalence of PAOF is growing. Identifying mechanisms for PAOF is attracting a considerable amount of research with no agreement on the mechanism(s). Our research on the heart and cardiovascular system, over the past 50-plus years, leads us to believe that major causes …

Genotoxic Effects Of Magnesium Deficiency In The Cardiovascular System And Their Relationships To Cardiovascular Diseases And Atherogenesis, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Bella T. Altura

The School of Health Sciences Publications and Research

The authors present evidence for a novel, new hypothesis whereby magnesium deficiency (MgD) acts as a genotoxic agent which probably causes numerous, hertofore, unrecognized consequences, even over a short-term, on the physiological, molecular and biochemical machinery of cardiovascular tissues and cells. The end result of these genotoxic effects of MgD probably plays important roles in the etiology and generation of diverse cardiovascular diseases, atherosclerosis, inflammation, and strokes via alterations in the epigenome of cardiovascular tissues and cells. The importance of adequate water-borne and dietary levels of Mg is emphasized.

Caspase-12, Rheumatoid Arthritis, And The Dog That Didn’T Bark, Evan Hermel

Faculty Publications & Research of the TUC College of Osteopathic Medicine

CASPASE-12 (CASP12) has an anti-inflammatory function during infection. To determine and if CASP12 could protect against inflammatory disease, we investigated the distribution of CASP12 alleles in African-Americans (AA) with rheumatoid arthritis (RA). CASP12 homozygous patients had lower baseline joint narrowing and total disease scores. However, there was no significant difference for distribution of CASP12 genotypes between AA controls and patients with RA, or any other clinical criteria for this disease. CASP12 homozygosity appears to be, at best a subtle protective factor for some aspects of RA in AA patients. This raises an intriguing issue as to how this protein would …

Caspase-12 And Lupus: The Curious Case Of The Dog That Didn’T Bark, Evan Hermel

Faculty Publications & Research of the TUC College of Osteopathic Medicine

CASPASE-12 (CASP12) has an anti-inflammatory function during infection, and is a risk factor for sepsis in African-Americans (AA). To determine if CASP12 could be protective for systemic lupus erythematosus (SLE) in AA, we genotyped AA SLE patients and controls. We found that, at best, there was a weak association between CASP12 genotype with the absence of anti-dsDNA autoantibodies in SLE patients. No effect was seen upon serum interleukin-1 beta levels, nor was any other protective effect noted for the CASP12 genotype, whether upon association with SLE, or any of the 11 American College of Rheumatology classification criteria. We concluded that …

The Anti-Inflammatory Caspase-12 Gene Does Not Influence Sle Phenotype In African-Americans, Trista Fuchs, Jennifer A. Kelly, Emily Simon, Kathy L. Sivils, Evan Hermel

Faculty Publications & Research of the TUC College of Osteopathic Medicine

No abstract provided.

Ppap2b Expression Limits Lesion Formation In Murine Models Of Atherosclerosis, Paul A. Mueller

Theses and Dissertations--Physiology

Coronary artery disease (CAD) is the leading cause of death in both men and women worldwide and is defined as a narrowing of the coronary arteries due to accumulation of atherosclerotic plaques. Genome-wide association studies have identified risk loci within the gene PPAP2B that confers increased risk of developing CAD. Evidence suggests these aforementioned SNPs are regulating PPAP2B expression in a cis-manner through the interruption of transcription factor binding sites. PPAP2B encodes the lipid phosphate phosphatase 3 enzyme that plays a key role in degrading bioactive lysophosphatidic acid (LPA). LPA has a plethora of effects on vascular tissue and is …

Post-Tbi Hippocampal Neurogenesis In Different Tbi Models, Kaushal S. Patel

Theses and Dissertations

Traumatic brain injury (TBI) leads to short-term and long-term consequences that can cause many different life-long disorders. Studies of TBI have generally focused on the acute stage; however, it is now becoming important to investigate chronic responses following TBI as clinical reports of dementia and cognitive impairments have been linked to a history of TBI. Recent data have established that cognitive function is associated with hippocampal neurogenesis. Chronic injury induced changes in the brain may affect this endogenous process. Chronic responses following TBI include cell death pathways and inflammatory responses that are persistent in the brain for months to years …

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 Departmental Research

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 …

Repression Of Esophageal Neoplasia And Inflammatory Signaling By Anti-Mir-31 Delivery In Vivo., Cristian Taccioli, Michela Garofalo, Hongping Chen, Yubao Jiang, Guidantonio Malagoli Tagliazucchi, Gianpiero Di Leva, Hansjuerg Alder, Paolo Fadda, Justin Middleton, Karl J. Smalley, Tommaso Selmi, Srivatsava Naidu, John L. Farber, Carlo M. Croce, Louise Fong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Overexpression of microRNA-31 (miR-31) is implicated in the pathogenesis of esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary zinc deficiency. Using a rat model that recapitulates features of human ESCC, the mechanism whereby Zn regulates miR-31 expression to promote ESCC is examined.

METHODS: To inhibit in vivo esophageal miR-31 overexpression in Zn-deficient rats (n = 12-20 per group), locked nucleic acid-modified anti-miR-31 oligonucleotides were administered over five weeks. miR-31 expression was determined by northern blotting, quantitative polymerase chain reaction, and in situ hybridization. Physiological miR-31 targets were identified by microarray analysis and verified by luciferase reporter …

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, …

Ultrasound Biomicroscopic Imaging For Interleukin-1 Receptor Antagonist-Inhibiting Atherosclerosis And Markers Of Inflammation In Atherosclerotic Development In Apolipoprotein-E Knockout Mice, Rong-Juan Li, Yan Sun, Qin Wang, Jiao Yang, Ya Yang, Li Song, Zheng Wang, Xiang-Hong Luo, Rui-Juan Su

The Texas Heart Institute Journal

We sought to validate the hypothesis that the development of atherosclerosis can be suppressed by the interleukin-1 receptor antagonist (IL-1Ra) in murine models of atherosclerosis in vivo, noninvasively seen by means of high-resolution ultrasound biomicroscopy, and we studied changes in inflammatory markers such as IL-1 and C-reactive protein (CRP) plasma levels in these models of atherosclerosis.

We divided IL-1Ra+/−/apolipoprotein-E (apoE)−/− and IL-1Ra+/+/apoE−/− mice into 2 age groups, used as atherosclerotic models. The control groups were age-matched IL-1Ra+/+/apoE+/+ mice. Plaque thickness was measured in the ascending aorta in short-axis images by means of ultrasound and histology. Plasma levels of IL-1 and …

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). …

Association Of Markers Of Inflammation With Sleep And Physical Activity Among People Living With Hiv Or Aids, Michael D. Wirth, Jason R. Jaggers, Wesley D. Dudgeon, James R. Hebert, Shawn D. Youngstedt, Steven N. Blair, Gregory A. Hand

Faculty and Staff Scholarship

This study examined associations of sleep and minutes spent in moderate-vigorous physical activity (MVPA) with C-reactive protein (CRP) and interleukin (IL)-6 among persons living with HIV (PLWH). Cross-sectional analyses (n=45) focused on associations of inflammatory outcomes (i.e., CRP and IL-6) with actigraph-derived sleep duration, latency, and efficiency; bedtime; wake time; and wake-after-sleep-onset; as well as MVPA. Least square means for CRP and IL-6 by levels of sleep and MVPA were computed from general linear models. Individuals below the median of sleep duration, above the median for bedtime, and below the median of MVPA minutes had higher CRP or IL-6 levels. …

Pharmaceutical Integrated Stress Response Enhancement Protects Oligodendrocytes And Provides A Potential Multiple Sclerosis Therapeutic., Sharon W Way, Joseph R Podojil, Benjamin L Clayton, Anita Zaremba, Tassie L Collins, Rejani B Kunjamma, Andrew P Robinson, Pedro Brugarolas, Robert H. Miller, Stephen D Miller, Brian Popko

Anatomy and Regenerative Biology Faculty Publications

Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-γ. In a mouse model of MS, experimental …

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 …

Vitamin C: A Potential Regulator Of Inflammatory Response, Bassem M. Mohammed

Theses and Dissertations

Introduction: Neutrophils (PMNs) and Macrophages are the first responders recruited consecutively to the site of injury/inflammation. PMNs’ response/fate as well as macrophage reprogramming ultimately determine the course of resolution of inflammation. Physiologic wound healing has a significant inflammatory component. An exaggerated inflammation however is self-defeating leading to delayed healing. Parenteral vitamin C (VitC) attenuated inflammation in murine sepsis models and in patients with sepsis. However information about the mechanisms by which VitC regulates these events is limited.

Methods: Humanized mice lacking VitC synthesis capability (Gulo^-/-) were used. VitC sufficient and deficient mice were challenged with sterile inflammation, or …

Nerve Growth Factor Regulates Neurolymphatic Remodeling During Corneal Inflammation And Resolution., Darci M. Fink, Alicia L. Connor, Philip M. Kelley, Maria M. Steele, Michael A. Hollingsworth, Richard M. Tempero

Journal Articles: Eppley Institute

The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF) increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that …

Microbiota, Oral Microbiome, And Pancreatic Cancer, Dominique S. Michaud, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Only 30% of patients diagnosed with pancreatic cancer survive one year post-diagnosis. Progress in understanding the causes of pancreatic cancer has been made, including solidifying the associations with obesity and diabetes, and a proportion of cases should be preventable through lifestyle modifications. Unfortunately, identifying reliable biomarkers of early pancreatic cancer has been extremely challenging, and no effective screening modality is currently available for this devastating form of cancer. Recent data suggest the microbiota may play a role in the disease process, but many questions remain. Future studies focusing on the human microbiome, both etiologically and as a marker of disease …

Effect Of Heme Oxygenase-1 On Matrix Metalloproteinase-3 Expression In Human Fibroblasts, Theresa A. Stangl

PCOM Biomedical Studies Student Scholarship

Heme oxygenase-1(HO-1) is an enzyme that plays a very important role in the resolution of inflammation. HO-1-based therapies are effective in a number of disease conditions. However, HO-1 also increases tumor growth, angiogenesis, metastasis and chemoresistance. Matrix metalloproteinase-3 (MMP-3) is an enzyme involved in physiological and pathophysiological tissue remodeling. Unbalanced expression of MMPs is a key feature of connective tissue destruction in chronic inflammatory conditions. Previously shown in this laboratory, the HO-1 inducer, hemin, increased MMP-3 mRNA expression in some HGF cultures. To assess whether HO-1 and/or its products regulate expression of MMP-3 in human fibroblasts, the effect of HO-1 …

Caspase-12 And Rheumatoid Arthritis In African-Americans, Laura Marshall, Mohammad Obaidullah, Trista Fuchs, Naomi S. Fineberg, Garland Brinkley, Ted R. Mikuls, Evan Hermel

Faculty Publications & Research of the TUC College of Osteopathic Medicine

CASPASE-12 (CASP12) has a downregulatory function during infection and thus may protect against inflammatory disease. We investigated the distribution of CASP12 alleles (#rs497116) in African-Americans (AA) with rheumatoid arthritis (RA). CASP12 alleles were genotyped in 953 RA patients and 342 controls. Statistical analyses comparing genotype groups were performed using Kruskal–Wallis non-parametric ANOVA with Mann–Whitney U tests and chi-square tests. There was no significant difference in the overall distribution of CASP12 genotypes within AA with RA, but CASP12 homozygous patients had lower baseline joint-narrowing scores. CASP12 homozygosity appears to be a subtle protective factor for some aspects of RA in AA …

Bioengineered Lysozyme Reduces Bacterial Burden And Inflammation In A Murine Model Of Mucoid Pseudomonas Aeruginosa Lung Infection, Charlotte C. Teneback, Thomas C. Scanlon, Matthew J. Wargo, Jenna L. Bement, Karl E. Griswold, Laurie W. Leclair

Dartmouth Scholarship

The spread of drug-resistant bacterial pathogens is a growing global concern and has prompted an effort to explore potential adjuvant and alternative therapies derived from nature's repertoire of bactericidal proteins and peptides. In humans, the airway surface liquid layer is a rich source of antibiotics, and lysozyme represents one of the most abundant and effective antimicrobial components of airway secretions. Human lysozyme is active against both Gram-positive and Gram-negative bacteria, ac

Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley

Dissertations and Theses (Open Access)

Hemophilia A is a clotting disorder caused by functional factor VIII (FVIII) deficiency. About 25% of patients treated with therapeutic recombinant FVIII develop antibodies (inhibitors) that render subsequent FVIII treatments ineffective. The immune mechanisms of inhibitor formation are not entirely understood, but circumstantial evidence indicates a role for increased inflammatory response, possibly via stimulation of Toll-like receptors (TLRs), at the time of FVIII immunization. I hypothesized that stimulation through TLR4 in conjunction with FVIII treatments would increase the formation of FVIII inhibitors. To test this hypothesis, FVIII K.O. mice were injected with recombinant human FVIII with or without concomitant doses …

The Effect Of Statins On Testosterone In Men And Women, A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Mary Schooling, Shiu Lun Au Yeung, Guy Freeman, Benjamin J. Cowling

Publications and Research

Background
Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates morethan other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statinsunexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would beexpected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins’ pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone.

Methods
A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, …