UMD Theses and Dissertations
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Item EXERCISE AND PREVALENCE AND FIRST ONSET DEPRESSION IN WOMEN OF CHILDBEARING AGE(2017) Kinsey, Celena; Slopen, Natalie; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Background: Major depressive disorder is the leading cause of disability disproportionately affecting women of reproductive age. Prior research suggests that exercise may be an effective preventative measure. Objective: To examine the association between exercise and current and first onset major depressive episodes (MDE) among women 20-45 years (n=8175) participating in National Epidemiologic Study of Alcohol and Related Conditions II (2004-2005). Methods: Logistic regression models were used to examine the relationship between exercise and MDE prevalence and incidence. Results: Some exercise was associated with elevated odds of first onset MDE, compared to no exercise, but this association was not significant after controlling for covariates (adjusted odds ratio = 0.87, 95% confidence interval:0.75-1.01). No other associations were observed. Conclusion: This study did not find evidence of an association between exercise and prevalence or incidence of MDE in reproductive-aged women. Future research with prospective study designs and objective exercise measures needed.Item Feasibility of An Online Survey Examining the Physical Activity Patterns Among South Asian Adults Residing In the United States(2016) Haider, Syeda Rabab Zehra; Butler III, James; Public and Community Health; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Background: Physical inactivity is a major risk factor for cardiovascular disease and diabetes among South Asians (SAs) - Bangladeshi, Bhutanese, Indian, Maldivian, Nepali, Pakistani, and Sri Lankan. Methods: An online survey was used to determine the feasibility of examining physical activity (PA) levels of SAs living in the US. The Social Ecological Model was the theoretical basis for identifying individual-level, social environmental, and physical environmental factors that impact PA. Results: Ethnicity, intention, self-efficacy, and perceived health benefits of PA were significantly associated with being physically active. Facilitators to PA included achieving improved health; while barriers were lack of time to exercise, unfamiliarity with PA, and nonexistent gender-specific PA facilities. Conclusions: This study showed that online surveys can be a promising tool for data collection among SAs. Health promotion programs should include education on the benefits of PA, and provide culturally sensitive facilities that support PA, especially for SA women.Item EFFECTS OF CARDIOVASCULAR DISEASE AND PHYSICAL INACTIVITY ON THE PARACRINE FUNCTION OF CIRCULATING ANGIOGENIC CELLS(2015) Landers-Ramos, Rian Quinn; Hagberg, James M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Cardiovascular disease (CVD) is the leading cause of death in developed countries. Traditional cardiovascular risk factors account for only a fraction of events related to CVDs, emphasizing the need for investigations into more novel risk factors. Circulating angiogenic cells (CACs) are involved in the repair and maintenance of the vascular endothelium and function mainly through paracrine mechanisms. The studies presented in this dissertation provide new insight into differences in the paracrine actions of CACs as a function of habitual physical activity and CVD. The first study presented identifies, for the first time, that secreted factors from CD34+ and CD34-/CD31+ CACs affect HUVEC tube formation as a function of habitual physical activity. Study #1 identifies inflammatory proteins S100A8 and S100A9 as major factors contributing to the depressed tube formation observed when using CD34-/CD31+ conditioned media (CM) from inactive younger adults compared to endurance-trained athletes. The second study aimed to confirm the effects of S100A8 and S100A9 in CD34-/CD31+ CM on HUVEC tube formation in CVD patient populations compared to endurance-trained athletes. Study #2 found that the CM from non-ST- segment elevation myocardial infarction (NSTEMI) patient CD34-/CD31+ CACs impaired tube formation compared to athletes’ CM, and that pretreatment of HUVECs with an inhibitor for TLR4, a major receptor for S100A8 and S100A9, rescued tube formation to the levels observed when using CD34-/CD31+ CM from athletes. Higher S100A8 and S100A9 content was found in the CM of NSTEMIs compared to athletes. Finally, the study #2 mechanistically demonstrated the direct role of S100A8 and S100A9 on tube formation using recombinant S100A8 and S100A9 and confirmed that these actions were mediated by TLR4. Preliminary data in study #2 suggest that cell surface markers on selected CD34-/CD31+ CACs are inherently different between NSTEMI patients and endurance-trained athletes with lower presence of T-cell and monocyte markers on the CD34-/CD31+ CACs of NSTEMI patients. Collectively, the two studies presented in this dissertation demonstrate that both physical inactivity and CVD alter the paracrine actions of CD34-/CD31+ CACs which in turn impair HUVEC tube formation. These findings are of particular importance as new methods to improve CAC function for therapeutic purposes are being developed.Item The Effect of a 10 day Cessation of Training in Older Endurance Athletes on Pathological Production of Nitric Oxide and Reactive Oxygen Species Levels in Circulating Angiogenic Cells(2015) Corrigan, Kelsey J.; Hagberg, James; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Cardiovascular disease (CVD) is a serious disease, and is the leading cause of death in the United States. Aging and physical inactivity are two well-established risk factors for CVD. Previous research has identified circulating angiogenic cells (CACs) as a novel risk factor for CVD. CAC number and function are affected by aging and exercise. Nitric oxide (NO) and reactive oxygen species (ROS) are intracellular compounds which can affect the health of the vasculature and are also affected by exercise. Endothelial nitric oxide synthase (eNOS) is responsible for NO production within the endothelium, and eNOS "coupling" is a phenomenon that plays a role in the balance between production of ROS and NO. The literature also indicates that NO can be produced in either a pathological or physiological capacity depending on which isoform of NOS produces it. NO and ROS have been previously measured in CACs and have been shown to affect in vivo and in vitro outcomes related to vascular function. Although NO, ROS, and CACs have all been studied in relation to exercise, no previous studies have examined how the cessation of training in older endurance-trained athletes affects these intra-cellular compounds through the eNOS-coupling pathway. The purpose of this study was to examine the effect of a 10-day cessation of exercise training in older endurance-trained athletes on ROS, NO and the eNOS-coupling pathway in CD34+ cells. NO and ROS were measured in isolated fresh CD34+ cells using fluorescent dye assays. The mRNA expression of genes involved in the eNOS-coupling pathway (endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), dihydrofolate reductase (DHFR), and guanosine triphosphate cyclohydrolase 1 (GTPCH1)) were measured using semi-quantitative Polymerase Chain Reaction (Semi-qt PCR). Flow mediated dilation was measured to gain information about endothelial function. No significant differences were detected after the cessation of training in CD34+ intracellular NO or ROS levels. Flow mediated dilation (FMD) also did not change significantly following cessation of training. eNOS mRNA expression was significantly lower following cessation of training but iNOS, DHFR, and GTPCH1 did not change. Taking into consideration the current literature, we expected to see changes in all of the above variables with the cessation of exercise training. There were several limitations present in our study, which could have affected our outcomes. Research in this area, specifically the eNOS coupling pathway, is still very new and this study shows that additional research is still needed to elucidate the underlying mechanisms in CACs.Item REGULATORY EFFECTS OF ACUTE AND CHRONIC ENDURANCE EXERCISE ON NITRIC OXIDE AND REACTIVE OXYGEN SPECIES IN HUMAN CIRCULATING ANGIOGENIC CELLS(2011) Jenkins, Nathan Thomas; Hagberg, James M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This dissertation research comprised three studies examining the effects of acute and chronic endurance exercise on circulating angiogenic cells (CACs). Because the balance between nitric oxide (NO) and reactive oxygen species (ROS) is a critical aspect of the physiological function/dysfunction of CACs, each study determined the effects of exercise on NO-ROS balance within a variety of CAC types. Study #1 demonstrated that regular endurance exercise is associated with greater basal intracellular NO levels in cultured CACs, and that one mechanism underlying this association was increased NADPH oxidase enzyme activity in the sedentary state. Study #2 suggested an association between a sedentary lifestyle and increased nitro-oxidative stress in freshly-isolated CD34+ progenitor cells. Study #3 demonstrated that prior exercise attenuates high-fat meal induced-increases in mitochondrial-derived intracellular ROS in CD31+ CACs. Overall, it is concluded that acute and chronic endurance exercise enhance intracellular NO and ROS dynamics in CACs.Item DOES STRENGTH TRAINING IMPROVE MUSCULOSKELETAL HEALTH AND BODY COMPOSITION IN BLACK MEN WITH PROSTATE CANCER ON ANDROGEN DEPRIVATION THERAPY?(2011) Hanson, Erik; Hurley, Ben F; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Prostate cancer (PCa) is the most commonly diagnosed cancer in U.S. men and disproportionately affects black men more than any other racial or ethnic group. Despite this disparity, black men have been underrepresented in previous studies. PCa is commonly treated using androgen deprivation therapy (ADT). However, ADT induces numerous adverse side effects, including loss of muscle mass, strength, power, and physical function with concomitant increases in fat mass, fatigue, and bone fractures. Because strength training (ST) can reverse these factors in healthy older adults, it was hypothesized that ST would be effective in PCa patients on ADT but with an attenuated response. Therefore, the purpose of this study was 1) to examine the effects of ST on musculoskeletal and body composition side effects in black men on ADT, 2) to compare ST responses of black PCa patients on ADT to those of black healthy reference controls, and 3) to determine if changes in musculoskeletal health and body composition with ST are associated with changes in fatigue, physical function, and quality of life (QoL). PCa patients (N=17) completed a 12 week ST program, which produced many beneficial effects on factors adversely affected by ADT, including substantial gains in muscle power, size, strength, and endurance (all P < 0.001), resulting in a more favorable body composition (P < 0.001) and increased physical function (all P < 0.05). ST also improved fatigue perception and QoL (both P < 0.05). Compared with healthy reference controls (N=20), PCa patients responded to ST with similar gains in muscle power, strength, and mass, which was contrary to expectations. However, PCa patients had higher fat mass and lower muscle power and strength than controls at baseline (all P < 0.05). Finally, the changes in physical function, fatigue perception, and QoL were associated with some of the changes in muscle function with training. The findings in this study provide support for the hypothesis that ST improves musculoskeletal health and body composition in black men with PCa on ADT by demonstrating significant improvements in muscle power, mass, strength, and endurance, which can enhance physical function and QoL.Item Exercise and Depression: Causal Sequence Using Cross-Lagged Panel Correlation Analysis(2009) Scott, Virginia Anne; Andrews, David L; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This study sought to determine what kind of causal relationship, if any, exists between exercise and depression. A university student population (N = 178) was given the Godin Leisure Time Exercise Questionnaire and the Beck Depression Inventory-II at two time points separated by approximately one month. Cross-lagged panel correlation was used to make causal inferences based on the strength of the temporal relationships. After meeting the assumptions of synchronicity and stationarity, there was no significant difference between the cross-lagged correlations (ZPF = -0.4599, p = 0.65). Thus, no single causal pathway was dominant. While equal cross-lagged correlations can indicate spuriousness, it can also signify reciprocal causation. Exercise was not clearly the cause of reductions in depression, but neither was depression clearly the cause of physical inactivity. More complex causal pathways, such as reciprocal causation, warrant further investigation.Item THE EFFECT OF THROMBIN ON ENDOTHELIAL PROGENITOR CELLS WITH EXERCISE AND EXERCISE TRAINING.(2009) Lockard, Michael Morley; Hagberg, James; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)BACKGROUND: Circulating number of endothelial progenitor cells (EPCs) and EPC colony forming units (EPC-CFUs) have emerged as valuable predictors of cardiovascular health. Improvements in EPC number and EPC-CFUs have been associated with exercise and exercise training, although the mechanism for these improvements has not been identified. PURPOSE: This study examined the association of exercise-induced thrombin production with changes in circulating EPC number and EPC-CFUs as well as investigated the effects of exercise and thrombin supplementation on EPC differentiation and proliferation in vitro through gene expression analysis. METHODS: Subjects included healthy male Masters athletes (n = 12) and sedentary matched controls (n = 11) aged 55 - 80 years. Circulating EPC number, EPC-CFUs, plasma prothrombin fragment (F1+2) concentration and plasma thrombin-antithrombin III (TAT) concentration were measured at rest and after 30 minutes of vigorous treadmill exercise. Gene expression was assessed on resting EPC samples treated with 0U, 1U, 5U, or 10U of thrombin, as well as on EPC samples obtained after exercise. Gene expression analysis was performed for cell cycle genes cyclin A2, cyclin D1, and p27, and for cell surface markers VE-Cadherin and VEGFR2. To investigate the association of long-term exercise training, all outcomes were compared between Masters athletes and sedentary controls. RESULTS: Plasma concentrations of F1+2 and TAT increased significantly after exercise, however, EPC number and EPC-CFUs did not change. Changes in plasma F1+2 concentration with exercise correlated with changes in EPC number and EPC-CFUs in Masters athletes and with EPC number in control subjects Expression of the cell cycle genes cyclin A2 and cyclin D1 increased with thrombin treatment, while expression of the cell cycle inhibitor p27 decreased, peaking at 5U of thrombin. No change in VE-Cadherin or VEGFR2 expression was observed in control subjects, however, expression increased at 1U thrombin treatment in Masters athletes. Similarly, EPCs isolated after exercise demonstrated increased expression in cyclin A2 and cyclin D1, decreased in p27, and showed no change in VE-Cadherin or VEGFR2. CONCLUSION: Elevated thrombin production during vigorous exercise may play an important role in the regulation of EPCs, specifically cellular proliferation through changes in expression of cell cycle genes.Item The influence of visfatin and visfatin gene polymorphisms on glucose and obesity-related variables and their responses to aerobic exercise training(2008-08-12) McKenzie, Jennifer A; Hagberg, James M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Adipokines, soluble factors produced by adipocytes, may help to connect diabetes and obesity; one such adipokine is visfatin. Previous research has linked visfatin and visfatin gene (PBEF1) polymorphisms with glucose and obesity-related conditions; however, less is known regarding visfatin's response to an aerobic exercise training intervention, and no one, to our knowledge, has examined whether polymorphic variation in the PBEF1 gene affects aerobic exercise training-induced changes in glucose and obesity-related variables. Thus, this retrospective study investigated whether 6 months of aerobic exercise training reduced plasma visfatin levels in individuals with impaired glucose tolerance (IGT) or normal glucose tolerance (NGT). In addition, we examined the influence of common PBEF1 gene polymorphisms (-4689 G>T, -1543 C>T, -1001 T>G, -948 G>T, and SER301SER) and haplotypes on glucose and obesity-related variables and their responses to aerobic exercise training. Following the completion of 6 weeks of dietary stabilization, 116 healthy, sedentary, middle-aged, Caucasian men and women underwent 6 months of aerobic exercise training. Glucose total area under the curve (AUC), insulin AUC, and insulin sensitivity were measured via oral glucose tolerance tests. Plasma visfatin was measured using an enzyme immunoassay in 67 of the participants (22 with IGT, 45 with NGT), and standard techniques were used to assess lipoprotein-lipid and body composition variables. Restriction fragment length polymorphism techniques and TaqMan assays were used to determine PBEF1 genotypes. We found that plasma visfatin levels were comparable in IGT and NGT individuals at baseline and increased similarly in both groups in response to aerobic exercise training. We also found associations at baseline between glucose and obesity-related variables and PBEF1 gene variants, with -4689, -1001, -948, and SER301SER variant allele groups and PBEF1 variant allele-containing haplotypes having higher insulin sensitivity. Last, PBEF1 genetic variation influenced the aerobic exercise training-induced change in glucose and obesity-related variables. Moreover, the -948 polymorphism, TCGTT haplotype, and TCGGT haplotype were associated with lipoprotein-lipid changes with training, and the SER301SER polymorphism influenced changes in BMI and body fat. Future studies need to address the functional significance of PBEF1 polymorphisms and haplotypes and clarify mechanisms connecting visfatin to glucose and obesity-related phenotypes.Item The Effects of Low-Fat Diet and Exercise on C-Reactive Protein and Metabolic Syndrome: Findings from a Randomized Controlled Trial(2008-07-09) Camhi, Sarah Michelle; Young, Deborah R; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Background: Low-fat diet (D) and exercise (E) are recommended for reducing cardiovascular disease risk. However, the independent and combined effects of D and E on C-reactive protein (CRP) and metabolic syndrome (MS) are unknown. Purpose: The purpose of this dissertation was to examine the changes in CRP and MS between control (C), D, E and diet plus exercise (D+E). Methods: Men (n=197) and postmenopausal women (n=180) with elevated low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol, were randomized into a one-year trial with four groups: C, D, E or D+E (Stefanick et al., 1998). Weight loss was not an intervention focus. This secondary data analysis evaluated stored plasma samples for high-sensitivity CRP. MS prevalence was retrospectively found using the NCEP-ATP III definition. CRP change (ΔCRP) was examined between intervention groups using ANCOVA. Differences between groups for MS at follow-up were retrospectively investigated using logistic regression. All analyses were stratified by gender and controlled for baseline values, body fat change and other appropriate covariates. Results: In women, ΔCRP was different between D+E vs. C (-0.7 ± 0.33 mg/L, p = 0.04) and D+E vs. E (-0.9 ± 0.32 mg/L, p = 0.004). Women also had a decrease in CRP within D+E (Δ log CRP 0.2 ± 0.035 mg/L; p = 0.0002). After the intervention, ΔCRP did not differ for men between or within treatment groups. MS at follow-up was not different between C, D, E or D+E in either men or women. In women with MS, ΔCRP was different between D+E vs. C (-1.3 ± 0.43 mg/L; p = 0.006), D+E vs. E (-1.1 ± 0.44 mg/L; p = 0.02), and D vs. C (-1.2 ± 0.43 mg/L; p = 0.009). In women with MS, CRP decreased from baseline within D+E (Δ log CRP 0.2 ± 0.039 mg/L; p=0.0008). At follow-up, there were no differences between or within groups for ΔCRP in men with MS, or men without MS and women without MS. Conclusion: D and D+E may be effective treatments for reducing CRP in women with MS. Further studies are needed to replicate results and clarify the influence of gender.