Cardiovascular Diseases Commons^™

The Effects Of Dihydrobiopterin And Tetrahydrobiopterin On Hydrogen Peroxide And Nitric Oxide Release During Extracorporeal Shockwave Lithotripsy (Eswl), Brittany Deiling

PCOM Biomedical Studies Student Scholarship

ESWL is an effective, non-invasive therapy utilized to fragment stones in the kidney and subsequently be cleared in the urinary tract. Although lithotripsy provides a safer alternative to invasive treatments for removing stones, ESWL may cause vasoconstriction after ESWL treatment, reducing renal blood flow, which can cause kidney damage leading to acute to chronic hypertension clinically. This may be due to kidney vascular endothelial dysfunction, which is characterized as increased oxidative stress and decreased endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) bioavailability. We hypothesized that ESWL would decrease NO and increase hydrogen peroxide (H₂O₂) in …

Effect Of Chronic Angiotensin Ii Infusion On Plasma Tnfalpha And Il 6 Levels In Adiponectin Deficient Mice, Alexis O'Brien, Minnette Smith, Jaya Pamidimukkala

College of Osteopathic Medicine (TUN) Publications and Research

Chronic low grade inflammation plays an integral part in the development of many types of cardiovascular diseases. Adipose tissue is a well known source of many proinflammatory mediators. Adiponectin (APN) is one of the few proteins secreted by the adipose tissue that is known to have anti-inflammatory properties. Our research goal is to understand if APN deficiency contributes to a proinflammatory milieu especially when provided with an appropriate stimulus. Angiotensin II (ANGII) is a well known prohypertensive agent. Recently, ANGII has emerged as a growth factor and stimulator of proinflammatory cytokine expression in cardiovascular & renal tissue. The present study …

Testosterone, Cardiovascular, Men, Trial, Lin Xu, Guy Freeman, Benjamin J. Cowling, Mary Schooling

Publications and Research

Background
Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease.

Methods
A systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using “(“testosterone” or “androgen”) and trial and (“random*”)” with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, …

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, …

A Novel Selective Lipid Uptake Pathway Contributing To Ldl-Induced Macrophage Foam Cell Formation, Jason M. Meyer

Theses and Dissertations--Molecular and Cellular Biochemistry

Atherosclerosis is a disease characterized by cholesterol-rich plaques within the intima of medium and large arteries. Cholesterol deposition is thought to occur by infiltration of low-density lipoprotein (LDL) into lesions followed by uptake into macrophages, generating lipid-loaded “foam cells.” Foam cells can also be generated in vitro by treatment of macrophages with LDL or oxidized LDL (oxLDL). The purpose of the current investigation was to determine the contribution of selective cholesteryl ester (CE) uptake versus whole-particle uptake during LDL-induced foam cell formation in cultured macrophages. Murine bone marrow-derived macrophages (BMMs) exhibited significant cholesterol accumulation when treated with LDL as indicated …

The Morbidity & Mortality Of Prevalent Heart Failure, Jennifer Kwon

Loma Linda University Electronic Theses, Dissertations & Projects

The first study population included 292 unselected consecutive patients from the LLUMC heart failure clinic who were enrolled in the study from January to July 2006 and were followed up through the end of December 2010. The treatment policy at the clinic was to uptitrate dosages of beta-adrenergic blockade (β-blockers), angiotensin-converting-enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) to the most tolerable levels in order to reach target dosages, as recommended by the Heart Failure Society of America (HFSA). Patients were classified into systolic heart failure (ejection fraction (EF) < 40%) or diastolic heart failure (EF≥40%). All dosages of β-blockers, ACEi and ARB were extracted through chart reviews and were used as the main predictors of the patients' survival. Results from analyses showed that reaching target dosages of β-blockers and ACEi/ARB may increase survival when compared to not reaching target among the systolic HF population (HR_{β_biockers}= 0.64, 95% CI 0.26-1.56 and HR_ACEi/ARB=0.50, …

The Effects Of Supplemental Fish Oil On Blood Pressure And Morning Cortisol In Normotensive Adults: A Pilot Study, Eric E. Noreen, Josef Brandauer

Health Sciences Faculty Publications

Purpose: To determine the effects of 6wk of supplementation with fish oil (FO) on blood pressure and the morning salivary cortisol concentration in normotensive adults.

Methods: Testing was performed following an overnight fast. Subjects (n=40; 35+/-13y, mean+/-SD) rested supine for 40 min, at which time blood pressure and heart rate were measured. Saliva was collected and analyzed for cortisol. Subjects were then randomly assigned to either: 4g/d of Safflower Oil (SO); pr 4g/d of FO supplying 1,600mg/d eicosapentaenoic acid and 800mg/d docosahexaenoic acid. Testing was repeated following 6wk treatment.

Results: Compared to SO, there was a significant decrease …

Pediatric Pharmacogenomics: A Systematic Assessment Of Ontogeny And Genetic Variation To Guide The Design Of Statin Studies In Children., Jonathan B. Wagner, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

The dose-exposure-response relationship for drugs may differ in pediatric patients compared with adults. Many clinical studies have established drug dose-exposure relationships across the pediatric age spectrum; however, genetic variation was seldom included. This article applies a systematic approach to determine the relative contribution of development and genetic variation on drug disposition and response using HMG-CoA reductase inhibitors as a model. Application of the approach drives the collection of information relevant to understanding the potential contribution of ontogeny and genetic variation to statin dose-exposure-response in children, and identifies important knowledge deficits to be addressed through the design of future studies.

Characterization Of The Mechanism Of Pparγ-Mediated Neointima Formation In Rodents, Ryoko Tsukahara

Theses and Dissertations (ETD)

Lysophosphatidic acid (LPA) and its ether analog alkyl glycerophosphate (AGP) elicit arterial wall remodeling when applied intralumenally into the uninjured carotid artery. LPA is the ligand of eight GPCRs and the peroxisome proliferator-activated receptor γ (PPARγ). We pursued a gene knockout strategy to identify the LPA receptor subtypes necessary for the neointimal response in a non-injury model of carotid remodeling and also compared the effects of AGP and the PPARγ agonist rosiglitazone (ROSI) on balloon injury-elicited neointima development. In the balloon injury model AGP significantly increased neointima; however, rosiglitazone application attenuated it. AGP and ROSI were also applied intralumenally for …

Is Vitamin E Supplementation Effective In Reducing Mortality Related To Cardiovascular Events In People With Type 2 Diabetes Mellitus?, Payal Amin

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not Vitamin E is effective in reducing the mortality related to cardiovascular event in patients with Type 2 Diabetes mellitus.

Fetal Programming By Nicotine Increases Cardiac Susceptibility To Ischemic Injury, Jennifer Charlotte Alexie Lawrence

Loma Linda University Electronic Theses, Dissertations & Projects

Fetal programming is the area of study that focuses on the prenatal origins of adult onset disorders. Previous studies have associated an adverse prenatal environment with the onset of physiologic and metabolic diseases during adulthood. Fetal malnutrition, hypoxia, and exposure to drugs - such as cocaine and nicotine - have been associated with adult disease states. Cigarette smoking is the number one cause of preventable death in the developed world. Among the many dangerous chemicals found in tobacco products is nicotine, the compound responsible for the addictive nature of tobacco use. Nicotine use during pregnancy is a known cause of …

Atherosclerosis And Antioxidants, Yehoshua Lewis

The Science Journal of the Lander College of Arts and Sciences

Cellular lipid oxidation is a known cause for the cascade leading to the formation of lipid laden foam cells, which can cause of atherosclerosis. While statins and antioxidants have recently come under question in the amelioration of atherosclerosis, Flavonoids have recently been touted as a powerful antioxidant and suppresser of atherosclerosis. This paper will attempt to show why statins and vitamin E have come under scrutiny, and how the desired effects of Flavonoids can be attributed to the role it plays in increased paraoxonase-1 activity (a known anti inflammatory associated with HDL), decreased C- Reactive protein activity, and increased nitric …

Isoniazid Completion Rates For Latent Tuberculosis Infection Among College Students Managed By A Community Pharmacist, Karl M. Hess, Jeffery A. Goad, Joanne Wu, Kathleen Johnson

Pharmacy Faculty Articles and Research

Objective: The authors' objective was to document 9-month and previously recommended 6-month treatment completion rates for latent tuberculosis infection (LTBI) in a pharmacist-managed LTBI clinic in a community pharmacy oil a college Campus. and to describe patient characteristics. Participants: Participants were university Students diagnosed with LTBI. Methods: The authors conducted a retrospective review, of pharmacy records from 2000 to 2006. Main outcome measures included 6-month and 9-month LTBI treatment completion rates, total isoniazid (INH) tablets taken. characteristics of completers versus noncompleters. average time to treatment completion, and reported adverse drug events. Results: The 9-month completion rate was 59%, and the …

Composites Comprising Cholesterol And Carboxymethyl Cellulose, Vuk Uskoković

Pharmacy Faculty Articles and Research

Whereby cholesterol presents one of the major fatty substances in human body, carboxymethyl cellulose is a water-soluble derivative of cellulose, the most abundant dietary fiber. Whereas on one hand in vivo precipitation of cholesterol is the major cause of atherosclerosis, dietary fibers are on the other hand known for their ability to clean the fatty plaque deposited on intestinal pathways, and prevent its build-up in other critical areas within the organism. In this work, a method for the preparation of a composite material comprising cholesterol and carboxymethyl cellulose from 1-hexanol/water biphase mixtures is reported. Specificity of the interaction between the …

The Association Between Lifestyle Factors And Inflammatory Markers, Kerry Ann Stonebrook

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Cardiovascular disease (CVD) is the leading cause of death for both men and women in the United States. While smoking, high blood pressure, and elevated cholesterol levels are established risk factors for CVD, inflammation is being evaluated as a potential independent risk factor. A key cytokine regulator of the inflammatory response, interleukin-1 (IL-1), has emerged as playing a particularly important role at the genetic level in determining the degree to which the inflammation pathway is turned on. How an individual’s genetic make-up affects inflammation, CVD risk, and response to lifestyle intervention is an area of research that is in …

Probucol Prevents Early Coronary Heart Disease And Death In The High-Density Lipoprotein Receptor Sr-Bi/Apolipoprotein E Double Knockout Mouse, Anne Braun, Songwen Zhang, Helena E. Miettinen, Shamsah Ebrahim, Teresa M. Holm, Eliza Vasile, Mark J. Post

Dartmouth Scholarship

Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar/vesicular and stacked discoidal particles reminiscent of those in lecithin/cholesterol acyltransferase deficiency and cholestasis). Treatment …

Effect Of Monounsaturated Fat Rich Almonds On Hemostatic And Inflammatory Factors In Healthy Adults, Kristianne M. Connell

Loma Linda University Electronic Theses, Dissertations & Projects

Background: The frequent consumption of nuts is inversely associated with the incidence of cardiovascular disease. Nuts are known to decrease the risk of cardiovascular disease by reducing serum total and low-density lipoprotein (LDL) cholesterol. Markers of inflammation including C-reactive protein, E-selectin and interleukin-6 have been proposed to be newer risk factors for cardiovascular disease. However, the influence of nuts such as almonds on markers of inflammation and hemostasis that influence cardiovascular disease risk is not currently known.

Objective: The objective of this study was to determine the effect of almond consumption on markers of inflammation and hemostatic factors in healthy …

An Enzyme-Linked Immunosorbent Assay For The Detection Of Cardiac Myoglobin Using Monoclonal Antibodies, Deborah F. Kelly

Chemistry & Biochemistry Theses & Dissertations

The most prevalent life-threatening disease worldwide, secondary to coronary artery thrombosis is Acute Myocardial Infarction (AMI). Increases in three clinical markers have been explored as an early means of AMI detection: Cardiac myoglobin, and the two specific cardiac isoforms of Creatine Kinase, CK-MM and CK-MB. However, myoglobin levels have shown to give a more accurate correlation (R = 0.89) than does Creatine Kinase evaluation. Therefore, we have developed a two-site Enzyme-Linked Immunosorbent Assay (ELISA) using monoclonal antibodies against myoglobin isolated from human heart tissue. This assay is based on specific anti-genantibody interactions and is sensitive at the nanogram level. We …

Autonomic Nervous System And Cholesterol Transport, Yuan-Line Hung

Loma Linda University Electronic Theses, Dissertations & Projects

The effect of autonomic nervous system on cholesterol transport is of clinical interest because the relationship between lipoprotein metabolism and atherogenesis is expressed in coronary artery disease.

Generally speaking, beta blockers increase serum VLDL level but decrease both HDL and HDL₂ cholesterol levels without affecting the LDL in humans. We are unaware of reports concerning the effects of metoprolol on lipoprotein metabolism nor comparison of the effects of metoprolol and propranolol in the unhandled rat model. In part I we employed the unhandled rats to compared the effects of these 2 drugs administered with the drinking water in order …

Hemoglobin E B-Thalassemia In A Pakistani Family, Aftab Ahmed, Atiya Abbasi, Gerhard Braunitzer, Zafar H. Zaidi

Pharmacy Faculty Articles and Research

Hemoglobin E is a slow moving B chain variant of hemoglobin, first discovered by Itano¹. Characterized by Hunt et al² showed glutamic acid at B 26 to be replaced by lysine. It is a common variant of hemoglobin in the world and reported in high frequency from South-East Asia^3-6. Cases of Hb E, in combination with thalassemia have been reported on the basis of electrophoretic pattern only. In this communication a case of Hb E with B thalassemia is reported on the basis of amino acid sequencing of the abnormal peptide.

Insulin And Glucagon Responses To Dietary Protein In Diabetic And Nondiabetic Men, Monica L. Blomstedt

Loma Linda University Electronic Theses, Dissertations & Projects

Five men with non-insulin-dependent diabetes mellitus and fourteen nondiabetic men, were given test meals with soy protein, casein or additional carbohydrate in place of protein. Blood levels of insulin, glucagon, glucose and lipids were measured at fasting, one-half hour and two hours postprandial. To all meals, the nondiabetic subjects responded with a quick rise of the insulin level which decreased at two hours. In contrast, the diabetics showed a significantly lower insulin response at one-half hour (p < 0.05), but a tendency to higher levels at two hours. The same pattern was observed in the insulin to glucagon ratio. No significant difference between the meals was found in regard to insulin or glucagon responses, suggests that a sustained, although delayed postprandial insulin response, may be a precursor to the higher cholesterol and increased risk for cardiovascular disease among diabetics.

The Relationship Of Vitamins B-6 And B-12 To Plasma Homocysteine Levels In Men At Low- And High-Risk For Coronary Heart Disease, Marlene E. Swift

Loma Linda University Electronic Theses, Dissertations & Projects

There is evidence that homocysteine may be a factor in increasing the risk of coronary heart disease (CHD). To explore this relationship further, we assessed the interrelation of dietary vitamins B-6, B-12 and folate, and plasma pyridoxal-5'-phosphate and vitamin B-12 with plasma free and protein-bound homocysteine levels. Fasting blood and three-day dietary records were obtained from nine men low-risk (LR) and five at high-risk (HR) for CHD. The HR mean systolic blood pressure, total cholesterol (TC), and TC/cholesterol ratios were significantly higher than LR levels. Groups were comparable by age, weight, height, skinfolds, exercise, and smoking history. No significant difference …

The Effect Of Dietary Alpha - Linolenic Acid On Apparent Risk Factors Of Cardiovascular Disease, Kelvin D. Lindbeck

Loma Linda University Electronic Theses, Dissertations & Projects

Eight healthy male lacto-ovo-vegetarian subjects averaging 28.0 ± 3.6 years of age (22 to 53 years) were fed a diet rich in α-linolenic acid (18:3 ω 3) for four weeks. Arterial blood pressure and body weight were recorded each week. Plasma 6-keto-prostaglandin F_1α (6-keto- PGF_1α ), thromboxane B₂ (TXB₂), total cholesterol, triglyceride, and total phospholipid fatty acid composition were analyzed at 0, 2 and 4 weeks.

Systolic blood pressure increased significantly between weeks 0 and 1 (106.5 ± 2.7 mmHg to 114.0 ± 3.7 mmHg; p < 0.003), but decreased to 107.3 t 2.6 mrHg (p < 0.02) at week 2. There was an insignificant increase in both systolic and diastolic blood pressures after four weeks. There was no significant change in either total cholesterol or triglyceride levels during the four weeks.

Plasma 6-keto-PGF_1α levels increased significantly from 60.13 ± …

Development Of A Procedure For Analysis Of High Density Lipoprotein Subclasses, Chan Chin

Chemistry & Biochemistry Theses & Dissertations

Human serum high density lipoprotein subclasses, HDL₂ and HDL₃ , were isolated by preparative salt density gradient ultracentrifugation and further analyzed by electrophoresis on a 4 to 15% concentration gradient polyacrylamide gel.

The separation of the major classes of serum lipoproteins was achieved after a single ultracentrifugation for 272,000 g at 15°c in a swinging bucket rotor. High resolution concentration gradient gel electrophoresis was found to be particularly suitable for the separation of lipoproteins. The isolation of HDL by precipitation methods, heparin-manganese and dextran-magnesium have also been evaluated in this study, and were found not to completely separate …