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- All Subjects: Physiology
- Creators: Johnston, Carol
- Member of: Theses and Dissertations
Description
ABSTRACT The hormone leptin is an important regulator of body weight and energy balance, while nitric oxide (NO) produced in the blood vessels is beneficial for preventing disease-induced impaired vasodilation and hypertension. Elevations in the free radical superoxide can result in impaired vasodilation through scavenging of NO. Omega 3 is a polyunsaturated fatty acid that is beneficial at reducing body weight and in lowering many cardiovascular risk factors like atherosclerosis. The present study was designed to examine the change in plasma concentrations of leptin, nitric oxide, and the antioxidant superoxide dismutase in addition to examining the association between leptin and NO in healthy normal weight adult female subjects before and following omega 3 intakes. Participants were randomly assigned to either a fish oil group (600 mg per day) or a control group (1000 mg of coconut oil per day) for 8 weeks. Results showed no significant difference in the percent change of leptin over the 8 week supplementation period for either group (15.3±31.9 for fish oil group, 7.83±27 for control group; p=0.763). The percent change in NO was similarly not significantly altered in either group (-1.97±22 decline in fish oil group, 11.8±53.9 in control group; p=0.960). Likewise, the percent change in superoxide dismutase for each group was not significant following 8 weeks of supplementation (fish oil group: 11.94±20.94; control group: 11.8±53.9; p=0.362). The Pearson correlation co-efficient comparing the percent change of both leptin and NO was r2= -0.251 demonstrating a mildly negative, albeit insignificant, relationship between these factors. Together, these findings suggest that daily supplementation with 600 mg omega 3 in healthy females is not beneficial for improving these cardiovascular risk markers. Future studies in this area should include male subjects as well as overweight subjects with larger doses of fish oil that are equivalent to three or more servings per week. The importance of gender cannot be underestimated since estrogen has protective effects in the vasculature of females that may have masked any further protective effects of the fish oil. In addition, overweight individuals are often leptin-resistant and develop impaired vasodilation resulting from superoxide-mediated scavenging of nitric oxide. Therefore, the reported antioxidant and weight loss properties of omega 3 supplementation may greatly benefit overweight individuals.
ContributorsAlanbagy, Samer (Author) / Sweazea, Karen (Thesis advisor) / Johnston, Carol (Committee member) / Shepard, Christina (Committee member) / Lespron, Christy (Committee member) / Arizona State University (Publisher)
Created2014
Description
The omega-3 fatty acids in fatty fish and fish oil, eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), have been associated with a reduction in risk for cardiovascular disease. Blood type is a known contributor to risk for cardiovascular events. This study evaluated the effect of fish oil supplements on cardiovascular risk markers in adults with blood types A or O. An 8-week parallel-arm, randomized, double-blind trial was conducted in healthy adult men and women with either blood type A (BTA) or blood type O (BTO). Participants were randomized to receive fish oil supplements (n=10 [3 BTA/7 BTO]; 2 g [containing 1.2 g EPA+DHA]/d) or a coconut oil supplement (n=7 [3 BTA/4 BTO]; 2 g/d). Markers that were examined included total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), high-sensitivity C-reactive protein (hsCRP), and hemoglobin A1C (HbA1C). Results indicated that the percent change in LDL cholesterol was significantly greater in the coconut oil group vs the fish oil group (-14.8±12.2% vs +2.8±18.9% respectively, p=0.048). There were no other significant differences between treatment groups, or between blood types A and O, for the other cardiovascular risk markers. Further research with a larger and more diverse sample may yield a more conclusive result.
ContributorsHerring, Dana (Author) / Johnston, Carol (Thesis advisor) / Vega-Lopez, Sonia (Committee member) / Shepard, Christina (Committee member) / Arizona State University (Publisher)
Created2014
Description
Following a traumatic brain injury (TBI) 5-50% of patients will develop post traumatic epilepsy (PTE). Pediatric patients are most susceptible with the highest incidence of PTE. Currently, we cannot prevent the development of PTE and knowledge of basic mechanisms are unknown. This has led to several shortcomings to the treatment of PTE, one of which is the use of anticonvulsant medication to the population of TBI patients that are not likely to develop PTE. The complication of identifying the two populations has been hindered by the ability to find a marker to the pathogenesis of PTE. The central hypothesis of this dissertation is that following TBI, the cortex undergoes distinct cellular and synaptic reorganization that facilitates cortical excitability and promotes seizure development. Chapter 2 of this dissertation details excitatory and inhibitory changes in the rat cortex after severe TBI. This dissertation aims to identify cortical changes to a single cell level after severe TBI using whole cell patch clamp and electroencephalogram electrophysiology. The work of this dissertation concluded that excitatory and inhibitory synaptic activity in cortical controlled impact (CCI) animals showed the development of distinct burst discharges that were not present in control animals. The results suggest that CCI induces early "silent" seizures that are detectable on EEG and correlate with changes to the synaptic excitability in the cortex. The synaptic changes and development of burst discharges may play an important role in synchronizing the network and promoting the development of PTE.
ContributorsNichols, Joshua (Author) / Anderson, Trent (Thesis advisor) / Neisewander, Janet (Thesis advisor) / Newbern, Jason (Committee member) / Arizona State University (Publisher)
Created2014
Description
Long term high fat diets (HFD) are correlated with the development of diabetes
and kidney disease. However, the impact of short term high fat intake on the etiology of kidney disease has not been well-studied. Therefore, this study examined the impact of a six week HFD (60% fat) on kidney structure and function in young male Sprague-Dawley rats. Previous studies have shown that these animals develop indices of diabetes compared to rats fed a standard rodent chow (5% fat) for six weeks. The hypothesis of this study is that six weeks of HFD will lead to early stages of kidney disease as evidenced by morphological and functional changes in the kidney. Alterations in morphology were determined by measuring structural changes in the kidneys (changes in mass, fatty acid infiltration, and structural damage). Alterations in kidney function were measured by analyzing urinary biomarkers of oxidative RNA/DNA damage, renal tissue lipid peroxidation, urinary markers of impaired kidney function (urinary protein, creatinine, and hydrogen peroxide (H2O2)), markers of inflammation (tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6)), as well as cystatin C, a plasma biomarker of kidney function. The results of these studies determined that short term HFD intake is not sufficient to induce early stage kidney disease. Beyond increases in renal mass, there were no significant differences between the markers of renal structure and function in the HFD and standard rodent chow-fed rats.
and kidney disease. However, the impact of short term high fat intake on the etiology of kidney disease has not been well-studied. Therefore, this study examined the impact of a six week HFD (60% fat) on kidney structure and function in young male Sprague-Dawley rats. Previous studies have shown that these animals develop indices of diabetes compared to rats fed a standard rodent chow (5% fat) for six weeks. The hypothesis of this study is that six weeks of HFD will lead to early stages of kidney disease as evidenced by morphological and functional changes in the kidney. Alterations in morphology were determined by measuring structural changes in the kidneys (changes in mass, fatty acid infiltration, and structural damage). Alterations in kidney function were measured by analyzing urinary biomarkers of oxidative RNA/DNA damage, renal tissue lipid peroxidation, urinary markers of impaired kidney function (urinary protein, creatinine, and hydrogen peroxide (H2O2)), markers of inflammation (tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6)), as well as cystatin C, a plasma biomarker of kidney function. The results of these studies determined that short term HFD intake is not sufficient to induce early stage kidney disease. Beyond increases in renal mass, there were no significant differences between the markers of renal structure and function in the HFD and standard rodent chow-fed rats.
ContributorsCrinigan, Catherine (Author) / Sweazea, Karen (Thesis advisor) / Johnston, Carol (Committee member) / Mayol-Kreiser, Sandra (Committee member) / Arizona State University (Publisher)
Created2015
Description
Birds have plasma glucose levels that are 1.5-2 times greater than mammals of similar body mass in addition to higher free fatty acid concentrations, both of which would typically impair endothelium-dependent vasodilation if observed in mammals. Endothelium-dependent vasodilation can be stimulated in mammals through the use of acetylcholine (ACh), which primarily acts through nitric oxide (NO) and cyclooxygenase (COX)-mediated pathways, with varying reliance on endothelial-derived hyperpolarizing factors (EDHFs). Very few studies have been conducted on small resistance systemic arteries from birds. The hypothesis was that because birds have naturally high glucose and free fatty acid concentrations, ACh-induced vasodilation of isolated arteries from mourning doves (Zenaida macroura) would be independent of endothelial-derived factors and resistant to high glucose-mediated vascular dysfunction. Small resistance mesenteric and cranial tibial (c. tibial) arteries were pre-constricted to 50% of resting inner diameter with phenyleprine then exposed to increasing doses of ACh (10-9 to 10-5 μM) or the NO donor, sodium nitroprusside (SNP; 10-12 to 10-3 μM). For both vessel beds, ACh-induced vasodilation occurred mainly through the activation of potassium channels, whereas vasodilation of mesenteric arteries additionally occurred through COX. Although arteries from both vessel beds fully dilated with exposure to sodium nitroprusside, ACh-mediated vasodilation was independent of NO. To examine the effect of high glucose on endothelium-dependent vasodilation, ACh dose response curves were conducted following exposure of isolated c. tibial arteries to either a control solution (20mM glucose) or high glucose (30mM). ACh-induced vasodilation was significantly impaired (p = 0.013) when exposed to high glucose, but normalized in subsequent vessels with pre-exposure to the superoxide dismutase mimetic tiron (10 mM). Superoxide concentrations were likewise significantly increased (p = 0.0072) following exposure to high glucose. These findings indicate that dove arteries do not appear to have endogenous mechanisms to counteract the deleterious effects of oxidative stress. Additional studies are required to assess whether endogenous mechanisms exist to protect avian vascular reactivity from systemic hyperglycemia.
ContributorsJarrett, Catherine Lee (Author) / Sweazea, Karen L (Thesis advisor) / Johnston, Carol (Committee member) / Gaesser, Glenn (Committee member) / Arizona State University (Publisher)
Created2012
Description
The RAS/MAPK (RAS/Mitogen Activated Protein Kinase) pathway is a highly conserved, canonical signaling cascade that is highly involved in cellular growth and proliferation as well as cell migration. As such, it plays an important role in development, specifically in development of the nervous system. Activation of ERK is indispensable for the differentiation of Embryonic Stem Cells (ESC) into neuronal precursors (Li z et al, 2006). ERK signaling has also shown to mediate Schwann cell myelination of the peripheral nervous system (PNS) as well as oligodendrocyte proliferation (Newbern et al, 2011). The class of developmental disorders that result in the dysregulation of RAS signaling are known as RASopathies. The molecular and cell-specific consequences of these various pathway mutations remain to be elucidated. While there is evidence for altered DNA transcription in RASopathies, there is little work examining the effects of the RASopathy-linked mutations on protein translation and post-translational modifications in vivo. RASopathies have phenotypic and molecular similarities to other disorders such as Fragile X Syndrome (FXS) and Tuberous Sclerosis (TSC) that show evidence of aberrant protein synthesis and affect related pathways. There are also well-defined downstream RAS pathway elements involved in translation. Additionally, aberrant corticospinal axon outgrowth has been observed in disease models of RASopathies (Xing et al, 2016). For these reasons, this present study examines a subset of proteins involved in translation and translational regulation in the context of RASopathy disease states. Results indicate that in both of the tested RASopathy model systems, there is altered mTOR expression. Additionally the loss of function model showed a decrease in rps6 activation. This data supports a role for the selective dysregulation of translational control elements in RASopathy models. This data also indicates that the primary candidate mechanism for control of altered translation in these modes is through the altered expression of mTOR.
ContributorsHilbert, Alexander Robert (Author) / Newbern, Jason (Thesis director) / Olive, M. Foster (Committee member) / Bjorklund, Reed (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
The glycation of plasma proteins leading to the production of advanced glycation end products (AGEs) and subsequent damage is a driving factor in the pathophysiology of diabetic complications. The overall research objective was to elucidate the mechanisms by which birds prevent protein glycation in the presence of naturally high plasma glucose concentrations. This was accomplished through the specific purpose of examining the impact of temperature and glucose concentration on the percent glycation of chicken serum albumin (CSA) in comparison to human serum albumin (HSA). Purified CSA and HSA solutions prepared at four different glucose concentrations (0 mM, 5.56 mM, 11.11 mM, and 22.22 mM) were incubated at three different temperatures (37.0°C, 39.8°C, and 41.4°C) on separate occasions for seven days with aliquots extracted on days 0, 3, and 7. Samples were analyzed by LC-ESI-MS for percent glycation of albumin. The statistically significant interaction between glucose concentration, temperature, albumin type, and time as determined by four-way repeated measures ANOVA (p = 0.032) indicated that all independent variables interacted to affect the mean percent glycation of albumin. As glucose concentration increased, the percent glycation of both HSA and CSA increased over time at all temperatures. In addition, HSA was glycated to a greater extent than CSA at the two higher glucose concentrations examined for all temperature conditions. Temperature differentially affected percent glycation of HSA and CSA wherein glycation increased with rising temperatures for HSA but not CSA. The results of this study suggest an inherent difference between the human and chicken albumin that contributes to the observed differences in glycation. Further research is needed to characterize this inherent difference in an effort to elucidate the mechanism by which birds protect plasma proteins from glycation. Future related work has the potential to lead to the development of novel therapies to prevent or reverse protein glycation prior to the formation of AGEs in humans, thus preventing the development and devastating effects of numerous diabetic complications.
ContributorsZuck, Jessica (Author) / Sweazea, Karen (Thesis advisor) / Johnston, Carol (Committee member) / Lespron, Christy (Committee member) / Arizona State University (Publisher)
Created2016
Description
Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. When TBI occurs in children it often results in severe cognitive and behavioral deficits. Post-injury, the pediatric brain may be sensitive to the effects of TBI while undergoing a number of age-dependent physiological and neurobiological changes. Due to the nature of the developing cortex, it is important to understand how a pediatric brain recovers from a severe TBI (sTBI) compared to an adult. Investigating major cortical and cellular changes after sTBI in a pediatric model can elucidate why pediatrics go on to suffer more neurological damage than an adult after head trauma. To model pediatric sTBI, I use controlled cortical impact (CCI) in juvenile mice (P22). First, I show that by 14 days after injury, animals begin to show recurrent, non-injury induced, electrographic seizures. Also, using whole-cell patch clamp, layer V pyramidal neurons in the peri-injury area show no changes except single-cell excitatory and inhibitory synaptic bursts. These results demonstrate that CCI induces epileptiform activity and distinct synaptic bursting within 14 days of injury without altering the intrinsic properties of layer V pyramidal neurons. Second, I characterized changes to the cortical inhibitory network and how fast-spiking (FS) interneurons in the peri-injury region function after CCI. I found that there is no loss of interneurons in the injury zone, but a 70% loss of parvalbumin immunoreactivity (PV-IR). FS neurons received less inhibitory input and greater excitatory input. Finally, I show that the cortical interneuron network is also affected in the contralateral motor cortex. The contralateral motor cortex shows a loss of interneurons and loss of PV-IR. Contralateral FS neurons in the motor cortex synaptically showed greater excitatory input and less inhibitory input 14 days after injury. In summary, this work demonstrates that by 14 days after injury, the pediatric cortex develops epileptiform activity likely due to cortical inhibitory network dysfunction. These findings provide novel insight into how pediatric cortical networks function in the injured brain and suggest potential circuit level mechanisms that may contribute to neurological disorders as a result of TBI.
ContributorsNichols, Joshua (Author) / Anderson, Trent (Thesis advisor) / Newbern, Jason (Thesis advisor) / Neisewander, Janet (Committee member) / Qiu, Shenfeng (Committee member) / Stabenfeldt, Sarah (Committee member) / Arizona State University (Publisher)
Created2015
Description
Background: Vegan and vegetarian diets have gained in popularity in recent years. Stated reasons for this include some possible health benefits and concerns of animal welfare. Though considered to be nutritionally adequate, questions remain over whether current protein recommendations of 0.8 g/kg/d are sufficient to maintain body processes and growth. Protein is unique in that it is the only macronutrient that contains nitrogen. Its status can be determined through nitrogen balance analysis of the urine if protein content of the diet is known. Nitrogen balance is considered the gold standard for determining protein intake requirements. A negative balance indicates a catabolic state, whereas a positive nitrogen balance is seen during anabolism. In healthy people, nitrogen equilibrium is desired under normal circumstances. This equilibrium reflects the net synthesis and breakdown of proteins. While nitrogen balance techniques have been used for decades, currently, there are no known studies measuring nitrogen balance and protein intake in strict vegans. Methods: Twenty vegan, inactive, male participants were recruited and received a 5-day eucaloric diet with a known protein content held constant at 0.8 g/kg/d. On day five, 24-hour urine was collected by participants and aliquoted for future analysis. Nitrogen content of the urine was determined through photometric assay and compared to the known nitrogen content of the diet to calculate nitrogen balance status.
Results: Mean absolute nitrogen balance (-1.38 ± 1.22 g/d, effect size = -1.13) was significantly lower than zero (equilibrium) (p < .001). Mean relative nitrogen balance (-18.60 ± 16.96 mg/kg/d, effect size = -1.10) was significantly lower than zero (p < .001). There were no correlations seen between nitrogen balance and age, years as vegan, or fat- free mass.
Conclusion: Consuming 0.8 g/kg/d of protein is insufficient to produce nitrogen balance in long-term vegans.
ContributorsBartholomae, Eric (Author) / Johnston, Carol (Thesis advisor) / Sweazea, Karen (Committee member) / Wharton, Christopher (Committee member) / Lee, Chong (Committee member) / Kressler, Jochen (Committee member) / Arizona State University (Publisher)
Created2022
Description
Birds have the highest blood glucose concentrations of all vertebrates. Meanwhile, birds do not develop the same physiological complications (e.g., increased oxidative stress and glycation) that mammals do when blood glucose is elevated (i.e., diabetes). Therefore, birds may serve as a negative model animal for hyperglycemic complications. The physiological reason for high blood glucose in birds remains largely unknown although several unique characteristics of birds may contribute including a lack of the insulin responsive glucose transport protein, relatively high glucagon concentrations, as well as reliance on fatty acids to sustain the high energetic demands of flight. In breaking down triglycerides for energy, glycerol is liberated, which can be converted to glucose through a process called gluconeogenesis. In addition, the extent to which birds maintain homeostatic control over blood glucose in response to extreme dietary interventions remains unclear and few dietary studies have been conducted in wild-caught birds. Using Mourning Doves (Zenaida macroura) as a model organism, this dissertation tests four hypotheses: 1) Gluconeogenesis contributes to high circulating blood glucose concentration; 2-4) similar to mammals, a fully refined carbohydrate (i.e., white bread diet); a high saturated fat diet (60% kcal from fat); and an urban-type diet comprised of a 1:1 ratio of French fries and birds seed will increase blood glucose compared to a nutritionally-balanced diet after a four-week duration. Contrary to the hypothesis, 150 mg/kg Metformin (which inhibits glycerol gluconeogenesis) increased blood glucose, but 300 mg/kg resulted in no change. However, when 2.5 mg/kg of 1,4-dideoxy-1,4-imino-D-arabinitol (DAB; a glycogenolysis inhibitor) was given with 150 mg/kg of Metformin, blood glucose was not different from the control (50 ul water). This suggests that glycerol gluconeogenesis does not contribute to the naturally high blood glucose in birds and that a low dose of Metformin may increase the rate of glycogenolysis. In addition, all three experimental diets failed to alter blood glucose compared to control diets. Collectively, these results suggest that, in addition to a negative model for diabetes complications, birds can also serve a negative model for diet-induced hyperglycemia. Future research should further examine dietary manipulation in birds while controlling for and examining different variables (e.g., species, sex, duration, diet composition, urbanization).
ContributorsBasile, Anthony Joseph (Author) / Sweazea, Karen L (Thesis advisor) / Deviche, Pierre (Committee member) / Johnston, Carol (Committee member) / Trumble, Ben (Committee member) / Parrington, Diane J (Committee member) / Arizona State University (Publisher)
Created2022