Matching Items (28)
Description
Background: Despite the reported improvements in glucose regulation associated with flaxseeds (Linum usitatissimum) few clinical trials have been conducted in diabetic participants. Objective: To evaluate the efficacy of ground flaxseed consumption at attenuating hyperglycemia, dyslipidemia, inflammation, and oxidative stress as compared to a control in adults with non-insulin dependent type 2 diabetes (T2D). Design: In a randomized parallel arm controlled efficacy trial, participants were asked to consume either 28 g/d ground flaxseed or the fiber-matched control (9 g/d ground psyllium husk) for 8 weeks. The study included 17 adults (9 male, 8 females; 46±14 y; BMI: 31.4±5.7 kg/m2) with a diagnosis of T2D ≥ 6 months. Main outcomes measured included: glycemic control (HbA1c, fasting plasma glucose, fasting serum insulin, and HOMA-IR), lipid profile (total cholesterol, LDL-C, HDL-C, total triglycerides, and calculated VLDL-C), markers of inflammation and oxidative stress (TNF-alpha, TBARS, and NOx), and dietary intake (energy, total fat, total fiber, sodium). Absolute net change for measured variables (week 8 values minus baseline values) were compared using Mann-Whitney U non-parametric tests, significance was determined at p ≤ 0.05. Results: There were no significant changes between groups from baseline to week 8 in any outcome measure of nutrient intake, body composition, glucose control, or lipid concentrations. There was a modest decrease in TNF-alpha in the flaxseed group as compared to the control (p = 0.06) as well as a mild decrease in TBARS in the flaxseed as compared to the control group (p = 0.083), though neither were significant. Conclusions: The current study did not detect a measurable association between 28 g/d flaxseed consumption for 8 weeks in T2D participants and improvements in glycemic control or lipid profiles. There was a modest, albeit insignificant, decrease in markers of inflammation and oxidative stress in the flaxseed group as compared to the control, which warrants further study.
ContributorsRicklefs, Kristin (Author) / Sweazea, Karen L (Thesis advisor) / Johnston, Carol S (Committee member) / Gaesser, Glenn (Committee member) / Vega-Lopez, Sonia (Committee member) / Gonzales, Rayna (Committee member) / Arizona State University (Publisher)
Created2015
Description
ABSTRACT
Objective: The purpose of this randomized, placebo-controlled trial was to investigate the effect a daily coconut oil supplement (2 grams) would have on a common serum marker of systemic inflammation (C-reactive protein) and an indicator of oxidative stress (TBARS) when compared to the control group receiving a placebo capsule (white flour) in healthy, sedentary adults between the ages of 18-40 in Phoenix, Arizona.
Design: This study was designed as secondary analyses of blood samples originally collected to study the effects of coconut oil supplementation on blood lipids and body composition. The original study consisted of 32 healthy, adult volunteers recruited from the Arizona State University campus in Phoenix, Arizona. Participants followed no food restrictions or special diets, exercised less than 150 minutes per week, had no diagnoses of chronic disease, were not taking statin medications, were non-smokers, and no female participants were pregnant. Participants were randomized into either the Coconut Oil group (CO) or the Placebo group (PL) at week 0, and baseline blood samples and anthropometric measurements were obtained. Each participant completed an 8-week protocol consisting of two supplement capsules daily (coconut oil or placebo). Final fasting blood samples and anthropometric measurements were taken at week 8. This study analyzed the blood samples for measurements of C-reactive protein (CRP) and thiobarbituric reactive substance (TBARS).
Results: Eight weeks of 2 grams per day coconut oil supplementation, in comparison to placebo treatment, did not significantly reduce serum CRP ( -13% and +51% respectively, p=0.183) but did significantly increase TBARS ( +16% and -27% respectively, p=0.049).
Conclusions: Coconut oil supplementation (2 g/day) may impact lipid peroxidation as indicated by an increase in plasma TBARS concentration. Future trials are necessary to corroborate these results using other indices of fatty peroxide formation.
Objective: The purpose of this randomized, placebo-controlled trial was to investigate the effect a daily coconut oil supplement (2 grams) would have on a common serum marker of systemic inflammation (C-reactive protein) and an indicator of oxidative stress (TBARS) when compared to the control group receiving a placebo capsule (white flour) in healthy, sedentary adults between the ages of 18-40 in Phoenix, Arizona.
Design: This study was designed as secondary analyses of blood samples originally collected to study the effects of coconut oil supplementation on blood lipids and body composition. The original study consisted of 32 healthy, adult volunteers recruited from the Arizona State University campus in Phoenix, Arizona. Participants followed no food restrictions or special diets, exercised less than 150 minutes per week, had no diagnoses of chronic disease, were not taking statin medications, were non-smokers, and no female participants were pregnant. Participants were randomized into either the Coconut Oil group (CO) or the Placebo group (PL) at week 0, and baseline blood samples and anthropometric measurements were obtained. Each participant completed an 8-week protocol consisting of two supplement capsules daily (coconut oil or placebo). Final fasting blood samples and anthropometric measurements were taken at week 8. This study analyzed the blood samples for measurements of C-reactive protein (CRP) and thiobarbituric reactive substance (TBARS).
Results: Eight weeks of 2 grams per day coconut oil supplementation, in comparison to placebo treatment, did not significantly reduce serum CRP ( -13% and +51% respectively, p=0.183) but did significantly increase TBARS ( +16% and -27% respectively, p=0.049).
Conclusions: Coconut oil supplementation (2 g/day) may impact lipid peroxidation as indicated by an increase in plasma TBARS concentration. Future trials are necessary to corroborate these results using other indices of fatty peroxide formation.
ContributorsNorman, Lisa (Author) / Johnston, Carol (Thesis advisor) / Shepard, Christina (Committee member) / Ellis, Melissa (Committee member) / Arizona State University (Publisher)
Created2017
Description
Proper developmental fidelity ensures uninterrupted progression towards sexual maturity and species longevity. However, early development, the time-frame spanning infancy through adolescence, is a fragile state since organisms have limited mobility and responsiveness towards their environment. Previous studies have shown that damage during development leads to an onset of developmental delay which is proportional to the extent of damage accrued by the organism. In contrast, damage sustained in older organisms does not delay development in response to tissue damage. In the fruit fly, Drosophila melanogaster, damage to wing precursor tissues is associated with developmental retardation if damage is sustained in young larvae. No developmental delay is observed when damage is inflicted closer to pupariation time. Here we use microarray analysis to characterize the genomic response to injury in Drosophila melanogaster in young and old larvae. We also begin to develop tools to examine in more detail, the role that the neurotransmitter dopamine might play in mediating injury-induced developmental delays.
ContributorsContreras Rodriguez, Jesus (Co-author) / Lupone, Teresa (Co-author) / Beckett, Chaz (Co-author) / Almajan, Ashley (Co-author) / Leek, Ty (Co-author) / Hussain, Sabahat (Co-author) / Marsh, Tyler (Co-author) / Broatch, Jennifer (Co-author) / Hackney Price, Jennifer (Thesis director) / Sandrin, Todd (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Traumatic brain injury (TBI) is a leading cause of death in individuals under the age of 45, resulting in over 50,000 deaths each year. Over 80,000 TBI patients report long-term deficits consisting of motor or cognitive dysfunctions due to TBI pathophysiology. The biochemical secondary injury triggers a harmful inflammatory cascade, gliosis, and astrocyte activation surrounding the injury lesion, and no current treatments exist to alleviate these underlying pathologies. In order to mitigate the negative inflammatory effects of the secondary injury, we created a hydrogel comprised of hyaluronic acid (HA) and laminin, and we hypothesized that the anti-inflammatory properties of HA will decrease astrocyte activation and inflammation after TBI. C57/BL6 mice were subjected to mild-to-moderate CCI. Three days following injury, mice were treated with injection of vehicle or HA-Laminin hydrogel. Mice were sacrificed at three and seven days post injection and analyzed for astrocyte and inflammatory responses. In mice treated with vehicle injections, astrocyte activation was significantly increased at three days post-transplantation in the injured cortex and injury lesion. However, mice treated with the HA-Laminin hydrogel experienced significantly reduced acute astrocyte activation at the injury site three days post transplantation. Interestingly, there were no significant differences in astrocyte activation at seven days post treatment in either group. Although the microglial and macrophage response remains to be investigated, our data suggest that the HA-Laminin hydrogel demonstrates potential for TBI therapeutics targeting inflammation, including acute modulation of the astrocyte, microglia, and macrophage response to TBI.
ContributorsGoddery, Emma Nicole (Author) / Stabenfeldt, Sarah (Thesis director) / Addington, Caroline (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Duchenne Muscular Dystrophy (DMD) is a muscular degenerative disease characterized by striated membrane instability that stimulates continuous cycles of muscle repair. Chronic activation of the innate immune response necessary for muscle repair leads to a pathological accumulation of fibrotic materials that disrupt muscle function. During healthy tissue repair, a balance between pro-inflammatory macrophage (M1) and anti-inflammatory macrophage (M2) promotes clearance of necrotic fibers (myolysis) followed by tissue repair. This is regulated by an intricate feedback loop between muscle, neutrophils and macrophages mediated by Th1 and Th2 cytokines and chemokines. During chronic inflammation, there is an imbalance in an M2 species that produces high levels of extracellular matrix that leads to fibrosis. Finding treatments that ameliorate fibrosis are essential to limiting the muscle pathology that reduces ambulation of DMD patients. Previous studies have shown that Mohawk, (Mkx) a homeobox transcription factor, is essential for the initiation of the inflammation response during acute muscle injury. This study aims to examine whether Mkx regulates inflammation during chronic damage associated with muscular dystrophy. The mdx mouse is a well-studied mouse model that recapitulates muscle necrosis, chronic inflammatory response and fibrosis associated with muscular dystrophy. Utilizing quantitative RT-PCR and histological analysis, the diaphragms and Quadriceps of adult Mkx-/-/mdx and Mkx+/+/mdx mice were analyzed at three critical time points (4 weeks, 3 months and 7 months). In contrast to what was anticipated, there was evidence of increased muscle damage in the absence of Mkx. There was a consistent reduction in the diameter of muscle fibers found in both types of tissue in Mkx-/-/mdx versus Mkx+/+/mdx mice without a difference in the number of fibers with centralized nuclei at 4 weeks and 1 year between the two genotypes, suggesting that the Mkx mutation influences the maturation of fibers forming in response to muscle damage. Fibrosis was higher in the diaphragm of the Mkx-/-/mdx mice at 4 weeks and 3 months, while at1 year there did not appear to be a difference. Overall, the results predict that the absence of Mkx exacerbates the instability of muscle fibers in the mdx mouse. Future studies will be needed to understand the relationship between Mkx and the dystrophin gene.
ContributorsMasson, Samantha Ashley (Author) / Rawls, Alan (Thesis director) / Wilson-Rawls, Jeanne (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
In females, critical hormonal shifts occur during puberty, menstruation, pregnancy, and <br/>menopause. The fluctuating ovarian hormone levels across a woman’s lifespan likely contribute <br/>to inflammatory responses driven by the immune system, which is regulated by a variety of <br/>physiological pathways and microbiological cues. Pregnancy in particular results in drastic <br/>changes in circulating hormone profiles, and involves a variety of physiological changes, <br/>including inflammatory responses of the immune system. There is evidence that these effects are <br/>mediated, in part, by the significant hormone fluctuations that characterize pregnancy and <br/>postpartum periods. This thesis highlights and synthesizes important physiological changes <br/>associated with pregnancy, and their potential implications on cognitive and brain aging in <br/>women. A tertiary model of cognition is presented depicting interactions between hormonal <br/>history, reproductive history, and immune functions. This research is important to create a better <br/>understanding of women’s health and enhance medical care for women throughout pregnancy <br/>and across reproductive hormone shifts across the lifespan.
ContributorsLogan-Robledo, Santiago Rodrigo (Author) / Bimonte-Nelson, Heather A. (Thesis director) / Koebele, Stephanie V. (Committee member) / Simard, Alain (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
In a series of experiments during mid 1930s, a team of researchers in New York helped establish that bacteria of the species Toxoplasma gondii can infect humans, and in infants can cause toxoplasmosis, a disease that inflames brains, lungs, and hearts, and that can organisms that have it. The team included Abner Wolf, David Cowen, and Beryl Paige. They published the results of their experiment in Human Toxoplasmosis: Occurrence in Infants as an Encephalomyelitis Verification of Transmission to Animals. Toxoplasmosis is an infection that causes inflammations in the brain (encephalitis), heart (myocarditis), and lungs (pneumonitis). The disease is caused in organisms that consume items contaminated by the protozoan parasite Toxoplasma gondii. The bacteria can transfer from pregnant women to their fetuses during pregnancy (congenitally), and it can lead those fetuses to develop physical deformities and mental disabilities. The 1930s experiments established Toxoplasma gondii as a human pathogen and helped increase research into congenital toxoplasmosis, enabling later researchers to develop measures to prevent against the disease in pregnant women.
ContributorsPotestas, Jesse (Author) / Bartlett, Zane N. (Editor) / Arizona State University. School of Life Sciences. Center for Biology and Society. Embryo Project Encyclopedia. (Publisher) / Arizona Board of Regents (Publisher)
Created2015-06-11
Description
Skeletal muscle can intrinsically repair itself in response to injury. This repair process has been shown to be mediated through signaling of the innate immune system. The immune response caused during repair helps to clear away debris in damage and promotes the activation and proliferation of muscle stem cells (MuSCs) that will repair the damage muscle. Dysregulation of this inflammation leads to fibrosis and decreased efficacy of the repair process. Despite the requirement of inflammatory signaling during muscle repair, muscle’s contribution during inflammation as only recently started to be explored. The objective of this dissertation is to assess the contribution of muscle in the early inflammatory response during repair as well attempting to modulate this inflammation during disease to ameliorate disease pathology in a model of Duchenne’s muscular dystrophy. I tested the hypotheses that 1) muscle is an active participant in the early inflammatory response, 2) the transcription factor Mohawk (Mkx) is a regulator of the early inflammatory response and, 3) If this inflammation can be modulated with a virally derived serine protease inhibitor in a model of muscle disrepair and chronic inflammation. I found that muscle is actively participating in the establishment early inflammation in repair through the production of chemokines used to promote infiltration of immune cells. As well as the identification of a new muscle subtype that produces more chemokines compared to the average MuSC and upregulated genes in the Interferon signaling pathway. I also discovered that presence of this muscle subtype is linked to the expression of Mkx. In Mkx null mice this population is not present, and these cells are deficient in chemokine expression compared to WT mice. I subsequently found that, using the myxomavirus derived serine protease inhibitor, Serp-1 I was able to modulate the chronic inflammation that is common in those affected with Duchenne’s muscular dystrophy (DMD) utilizing a high-fidelity mouse model of the disease. The result of this dissertation provides an expanded role for muscle in inflammation and gives a potential new class of therapeutics to be used in disease associated with chronic inflammation.
ContributorsAndre, Alex (Author) / Rawls, Alan (Thesis advisor) / Wilson-Rawls, Jeanne (Committee member) / Kusumi, Kenro (Committee member) / Lake, Doug (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2022
Description
Intracerebral hemorrhage (ICH) is a devastating type of acute brain injury with high mortality and disability. Acute brain injury swiftly alters the immune reactivity within and outside the brain; however, the mechanisms and influence on neurological outcome remains largely unknown. My dissertation investigated how ICH triggers focal and systemic immune responses and their impact hemorrhagic brain injury. At the focal level, a significant upregulation of interleukin (IL)-15 was identified in astrocytes of brain sections from ICH patients. A transgenic mouse line where the astrocytic IL-15 expression is controlled by a glial fibrillary acidic protein promoter (GFAP-IL-15tg) was generated to investigate its role in ICH. Astrocyte-targeted expression of IL-15 exacerbated brain edema and neurological deficits following ICH. Aggravated ICH injury was accompanied by an accumulation of pro-inflammatory microglia proximal to astrocytes in perihematomal tissues, microglial depletion attenuated the augmented ICH injury in GFAP-IL-15tg mice. These findings suggest that IL-15 mediates the crosstalk between astrocytes and microglia, which worsens ICH injury.Systemic immune response was investigated by leveraging the novel method of obtaining and analyzing bone marrow cells from the cranial bone flaps of ICH patients. A swift increase of hematopoietic stem cell (HSCs) population in the bone marrow was identified, along with a shift towards the myeloid cell lineage. Human findings were mirrored in an ICH mouse model. Fate mapping these HSCs revealed increased genesis of Ly6Clow monocytes in the bone marrow, which transmigrate into the hemorrhagic brain and give rise to alternative activation marker bearing macrophage. Blockade of the β3-adrenergic receptor or inhibition of Cdc42 abolished ICH-induced myeloid bias of HSCs. Importantly, mirabegron, a Food and Drug Administration-approved β3 adrenergic receptor agonist, and a Cdc42 activator, IL-3, enhanced bone marrow generation of Ly6Clow monocytes and improved recovery. These results suggest that brain injury modulates HSC lineage destination to curb distal brain inflammation, implicating the bone marrow as a unique niche for self-protective neuroimmune interactions. Together, these results demonstrate how acute brain injury exerts a profound yet distinct effect on immune responses within and outside the brain and sheds new light on neuroimmune interactions with potential clinical implications.
ContributorsShi, Samuel Xiang-yu (Author) / Chang, Yung (Thesis advisor) / Liu, Qiang (Committee member) / Gonzales, Rayna J (Committee member) / Ducruet, Andrew F (Committee member) / Arizona State University (Publisher)
Created2020
Description
The need of organs for transplantation has become an increasing medical need due to a limited donor organ supply. Many organs fail within 10 years due to acute and chronic rejection. Acute or antibody mediated rejection leads to decreased long term graft survival and increases the need for a repeat transplant. In prior work, reducing endothelial heparan sulfation and blockade of chemokine-glycosaminoglycan (GAG) interaction with Myxomavirus-derived protein, M-T7, reduced aortic and renal graft vascular inflammation and rejection. Conditional endothelial Ndst1 deficiency and inhibition of chemokine-GAG interaction reduces early allograft damage and suggest new therapeutic options for graft rejection. Here acute renal rejection was examined in grafts with conditional endothelial N-deacetylase-N-sulfotransferase-1 knockout (Ndst1-/-) and in wildtype (WT) C57Bl6/J grafts treated with saline, M-T7, antisense oligonucleotides (ASO) for Ndst1 or a scrambled ASO control. Viruses have a highly adaptive ability to evade hosts defense and immune response. The immunomodulatory proteins derived from viruses provide potential therapeutic uses to alleviate this need for organs. The Myxoma virus derived protein M-T7 is a promising therapeutic for reducing kidney transplant rejection. Orthotopic transplantations in mice are extremely difficult and costly because they require a highly trained microsurgeon. This kidney to kidney subcapsular and subcutaneous transplant model is a practical and simpler method that requires fewer mice, one kidney can be used for transplants in 6 or more mice and there is much lower morbidity, pain and mortality. Heterotopic transplantation of allografts is a simple model for preliminary testing of treatments for early inflammation, ischemia, and graft rejection. Subcapsular kidney transplantation provides a first step approach to test virus-derived proteins as potential treatments to reduce transplant rejection and inflammation. This project reports on a broadly applicable platform on which to rapidly and conveniently test new treatments for transplant rejection. This finding will significantly lower the barrier to entry for labs which are interested in translating their laboratory findings to animal models of organ transplantation which is a complex surgical procedure, and thus accelerate the bench-to-bedside translation of novel, putative treatments for transplant rejection as an initial screening tool.
ContributorsBurgin, Michelle A (Author) / McFadden, Douglas (Thesis advisor) / Lucas, Alexandra R (Thesis advisor) / Yaron, Jordan R (Committee member) / Lim, Efrem S. (Committee member) / Hogue, Brenda G (Committee member) / Arizona State University (Publisher)
Created2020