Cardiovascular disease (CVD) is the leading cause of death in the United States, and the risk and severity of CVD are increased with type 2 diabetes. However, the exact mechanisms that result in the enhanced association between CVD and type 2 diabetes have not been clearly elucidated. Inflammation and oxidative stress are strongly implicated in both diseases. In type 2 diabetes, there is a dysregulation of inflammatory mediators where an anti-inflammatory molecule adiponectin and a pro-inflammatory cytokine TNF-alpha, are reduced and increased, respectively. Even lower plasma adiponectin concentrations are associated in type 2 diabetic patients with cardiovascular disease. Thus, adiponectin may be a significant link between the two diseases. The studies in this dissertation examined the in vivo cardioprotective actions of adiponectin and apocynin, a NADPH oxidase inhibitor, in the Zucker diabetic fatty (ZDF) type 2 diabetic model. A model of coronary artery occlusion was utilized to induce myocardial ischemia-reperfusion (I/R) injury. The mechanisms of protective actions were assessed by measures of inflammation, oxidative stress and DNA damage. Further, in vitro actions of adiponectin in human whole blood were investigated. We found that in vivo treatments of adiponectin and apocynin significantly reduced myocardial infarction in the type 2 diabetic heart by 40% and 68%, respectively. The cardioprotective action of adiponectin was associated with 2 to 4 fold significant attenuations in several inflammatory characteristics, such as neutrophil adhesion molecule CD11b expression, myocardial adhesion molecule ICAM-1 expression, myocardial neutrophil accumulation and plasma TNF-alpha concentration. The cardioprotective action of apocynin was associated with a significant reduction in myocardial oxidative stress by 25%. In vitro adiponectin actions demonstrated the ability of adiponectin to reduce neutrophil ROS production in human whole blood. These studies were the first to report the cardioprotective action of adiponectin in the type 2 diabetic heart. In addition, adiponectin was found to modulate neutrophil-mediated myocardial I/R injury. Collectively, these findings indicate the significant role of adiponectin in inflammation and oxidative stress in type 2 diabetes. Further, it can be concluded that inflammation and oxidative stress significantly contribute to the enhanced severity of injury observed in the type 2 diabetic heart.

Osteoarthritis, which affects over 21 million people and costs the US $61 billion/yr, is devastating the US population and taxing the health care system. These numbers will increase exponentially as the population ages. It is reported that previous trauma to cartilage resulting in focal chondral defects progresses to osteoarthritis if treatment is delayed or unsuccessful. Current treatment modalities for focal chondral defects have had variable success rates. As such scaffold based therapies in combination with tissue engineering are being developed as an alternative therapy for focal chondral defects. One important area of research to be addressed for these therapies to be successful is rapid integration of native tissue with the implant. An advantage of using scaffold based therapies is that scaffolds provide a stable surface for tissue to grow on and integrate with the existing tissue. In addition, there is the opportunity to use scaffolds for measuring joint loading. These measurements are crucial for a better understanding of the loading environment leading to osteoarthritis as well as for development of rehabilitation regimens when tissue engineering is used to treat defects. It is the goal of this research to determine if mimicking the native trabecular bone structure can be utilized to promote rapid bone ingrowth into implants and to determine whether these implants can be used to directly measure in vivo joint loads. To address the goals of this study, polybutylene terephthalate scaffolds were designed and then built using a fused deposition modeling system. Two different scaffold designs were utilized to determine if mimicking bone structure results in improved bone ingrowth. One scaffold was a biomimetic scaffold that replicated the trabecular bone structure and the other utilized a simple porous structure. These scaffolds were also equipped with strain gauges so that they could be used to monitor joint loading within the knee joint. The strain gauges were used in combination with implantable miniature radio transmitters to allow a fully internal measurement system to be used to determine joint loads during gait as well as other weight bearing activities. Using histology and μCT it was observed that the biomimetic scaffolds increased bone ingrowth into the scaffold over 500% compared to the simple porous scaffolds. These biomimetic scaffolds also increased bone growth in the areas adjacent to the scaffold. Additionally, it was demonstrated that these scaffolds when outfitted with strain gauges could measure axial joint loads occurring within the knee joint during various activities. It was noted that the temporal measurements were highly correlated with video analysis and that peak loads increased as a function of time post implantation. The ability of biomimetic scaffolds to increase bone ingrowth is important for anchoring the scaffold in place and allowing successful integration of tissue engineered cartilage with the native tissue. This will improve success rates of scaffold based tissue engineering therapies. The ability of implants to measure joint loads is crucial to developing a better understanding of osteoarthritis as well as improving rehabilitation protocols. Additionally, by monitoring the change in peak loads with time it will be possible to monitor the healing response at the implant site. Overall, this research demonstrates that polybutylene terephthalate scaffolds have the ability to be used in combination with tissue engineering constructs to treat focal chondral defects and are capable or providing direct in vivo loading measurements.

Gap junctions are aggregates of intercellular channels each formed of protein subunits termed connexins (Cx). Recently published data show that junctional dye permeability relative to conductance (permselectivity) varies across several orders of magnitude for Cx43 junctions, suggesting variable selectivity of the comprising Cx43 channels. Logical candidates for this variable selectivity are variability in charge or size selectivity. Consequently, junctional charge and size selectivities were determined in the current study by simultaneous measurement of junctional permeance to dyes of differing size or charge.The results show that for a number of dyes differing in size, charge, chemical composition, and structure the primary determinant for selectivity through Cx43 gap junctions was the size of the dye permeant with this selectivity showing essentially no variability beyond that seen between incompletely divided cells, presumably representing the variability inherent to the measurement. As such, selectivity of dye-permeable Cx43 channels is well described by the physical dimensions of the channel pore acting essentially as a simple molecular sieve. The seemingly disparate dye selectivity and permselectivity results can be reconciled by the variable presence of a dye-impermeable but electrically conductive channel conformation for Cx43 channels, affording a possible mechanism for independent regulation of diffusion of larger molecules versus electrical conductance to smaller ions.Cx40 junctions, known to be cation selective, also showed minimal variability in charge selectivity indicating that Cx40 charge selectivity is also an essentially fixed parameter. Co-expression of Cx40 and Cx43 lead to charge selectivities ranging from Cx43 to Cx40 with an average intermediate between the two. Activation of PKC leads to an increase in cationic selectivity of Cx40/Cx43 composed junctions by specifically reducing permeability through non-selective Cx43 channels favoring permeation through cation-selective Cx40 channels, allowing for junctional charge selectivity regulation.The combined data suggest that selectivity properties for dye permeable channels composed of Cx43 or Cx40 are essentially fixed parameters of the channel pore. Only upon co-expression of these connexins is significant variability in selectivity seen. The differential effects of PKC-mediated phosphorylation on permeability of Cx43 and Cx40 channels then allows for regulation of junctional charge selectivity but only in cells expressing both connexins.

Hypertension is involved in the exacerbation of stroke. Increased blood-brain barrier (BBB) permeability and cerebral edema formation are potentially lethal complications of cerebral infarction. It is unclear how BBB tight junction (TJ), ion transporter, and protein kinase C (PKC) signaling pathway proteins critical for maintaining brain homeostasis contribute to cerebral infarction during hypertension development. The hypothesis of this study is that hypertension leads to molecular changes in the BBB which predispose the brain to increased cerebral infarct damage following ischemic stroke. Studies were undertaken to investigate the effect of hypertension development on (1) physiological parameters of the spontaneously hypertensive rat (SHR) and on the expression levels of BBB TJ, ion transporter, and PKC proteins potentially involved in ischemia-induced infarct damage; (2) ischemia-induced infarct volume following permanent middle cerebral artery occlusion (MCAO); and (3) the effect of inhibition of Na+/H+ exchanger isoform 1 (NHE-1) on ischemia-induced infarct volume following permanent MCAO in hypertensive SHR (15 weeks). Early hypertension development was determined in SHR and compared to normotensive, age-matched Wistar-Kyoto (WKY) rats at 5 (pre-hypertension), 10 (early stage hypertension), and 15 (later stage hypertension) weeks of age. Characterization of BBB TJ and ion transporter proteins known to contribute to edema and fluid volume changes in the brain show differential protein expression patterns during hypertension development. Western blot analysis of TJ zonula occludens-2 (ZO-2) showed decreased expression while ion transporter, NHE-1 was markedly increased in hypertensive SHR (15 weeks) compared to age-matched controls. Hypertensive SHR (10 and 15 weeks) showed greatly increased necrotic volume with impaired neurological deficits and edema formation. Increased NHE-1 expression in hypertensive SHR (15 week) suggests a potential role for this ion transporter in the promotion of ischemic brain injury. Selective inhibition of NHE-1 using 5-(N,N-Dimethyl)amiloride (DMA) showed significant attenuation in ischemia-induced infarct volume in hypertensive SHR following MCAO. These data suggest a novel role for NHE-1 at the BBB/neurovascular unit in the regulation of ischemia-induced infarct volume in hypertensive SHR suggesting that modulation of NHE-1 may be a factor important in the potentiation of MCAO infarct size and a novel therapeutic target in the prevention of ischemic stroke.

No description available.

The rate and severity of hypertension are much lower in women than men of a similar age. However, the incidence of hypertension and its complications increase dramatically after menopause, matching and then surpassing that of age-matched males. While current anti-hypertensive therapeutics can improve blood pressure in males, they have proven to be less effective in postmenopausal women. Clinical trials in menopausal women utilizing hormone replacement therapy have also produced controversial results, thus other approaches are necessary to control blood pressure in women after menopause. Targeting the endothelin system can attenuate hypertension in male mice, and components of this system are known to be upregulated in females after menopause. Recent evidence in male mice also demonstrates that T lymphocytes promote the development of hypertension. However, research into the role of the endothelin and immune systems during hypertension in females is lacking, and is necessary to better understand how blood pressure regulation changes after menopause and identify novel targets for anti-hypertensive drug development. Therefore, we sought to determine how the progression to menopause in the novel VCD mouse model of menopause impacts the degree of angiotensin II (Ang II) hypertension and whether antagonizing the ET-1 system could attenuate hypertension in menopausal animals. We also hypothesized that prevention of T cell-mediated responses contributes to sex differences in hypertension and that the increased degree of hypertension after menopause requires T cells. To determine how the gradual progression to menopause in VCD-treated mice impacts hypertension, we infused Ang II into premenopausal and VCD-treated peri- and postmenopausal animals. Compared to premenopausal mice, Ang II-induced hypertensive responses were significantly increased after menopause, but were unchanged during the perimenopause transition. 17𝛽-estradiol replacement during perimenopause prevented the increased hypertensive response in menopausal animals, demonstrating that upregulation of hypertension in this model is driven by the loss of estrogen-induced protective actions. To test the hypothesis that ETA receptor-mediated signaling promotes postmenopausal hypertension, VCD-treated menopausal mice were administered either the ETA receptor antagonist ABT-627, 17𝛽-estradiol replacement, or vehicle. The increased hypertensive response in menopausal mice was equally prevented by either ETA receptor antagonism or 17𝛽-estradiol replacement, supporting the notion that ET-1-targetted drugs may improve blood pressure control in postmenopausal women. To address the hypothesis that prevention of T cell-mediated responses contributes to sex differences in hypertension, Ang II was infused into T cell-deficient male and premenopausal or VCD-treated menopausal female Rag-1^(-/-) mice with or without CD3⁺ T cell adoptive transfer. The results support this hypothesis, demonstrating that T cells promote the increased hypertensive response in males, and that the T cell-dependent response is prevented in premenopausal females, establishing sex differences in hypertension. After menopause, T cells are required for the increase in hypertension. To test the hypothesis that anti-inflammatory regulatory T cells are required for resistance against hypertension in premenopausal females, PC-61 was administered to deplete regulatory T cells during 14 days of Ang II infusion. We found that regulatory T cell depletion significantly increased the degree of Ang II hypertension, supporting a critical anti-hypertensive role for regulatory T cells in premenopausal female mice.

<p> The present study examined the effectiveness of progressive muscle relaxation (PMR) in relation to increasing well-being and decreasing stress and fatigue among athletes. Collegiate and club athletes from a Division I University (<i>n</i> = 30) completed three surveys, including a demographics questionnaire, the College Student Athlete Life Stress Scale, and the Subjective Exercise Experience Scale. Athletes were randomly selected into two groups and asked to partake in a 20-minute coping method either with a PMR session (<i>n</i> = 15; intervention) or lying comfortably (<i>n</i> = 15; control). The Subjective Exercise Experience Scale (SEES) was given as a pre and post assessment to examine the effectiveness of PMR. Results revealed stress and fatigue levels to decrease and well-being levels to increase for both groups. PMR and lying quietly had significant changes from pre to post intervention; both worked the same. The findings of this study were inconclusive; increased PMR sessions are needed.</p>

The purpose of this study was to investigate the functional relationship between the combined biofeedback, open focus, self-regulation technique and the physiological variables of oxygen consumption (l/m), heart rate (bpm), and systolic blood pressure (mm Hg) measured during a steady-state work condition. / Four university volunteer subjects, two males (ages 29 and 31) and two females (ages 26 and 29), were recruited. A variation of a multiple baseline across subjects design was used to establish a clear and stable baseline. Subjects were given a 20-session biofeedback open focus attention training treatment following the baseline sessions. Electromyographic and temperature feedback were given during the feedback sessions, in which a criterion of 1.5 microvolt mean, 95(DEGREES)F finger temperature mean, and 90(DEGREES)F toe temperature mean was established to demonstrate acquisition of the skill. / Subjects were retested at the same baseline workload after the 20-session training. Results were displayed graphically and the percentage reductions between baseline and the final testing were as follows: Heart rate--subject A, 3%; subject B, 6%; subject C, 11%; subject D, 14%. Oxygen consumption--subject A, 7%; subject B, 14%; subject C, 13%; subject D, 13%. Systolic blood pressure--subject A, 4%; subject B, 13%; subject C, 9%; subject D, 11%. The results indicated all but subject A had significantly improved the efficiency of pedaling the bicycle ergometer. / The proposed physiological mechanism for the biofeedback self-regulation process may be seen as organization by means of attentional cortical open focusing leading to bilateral brain hemisphere synchrony; this, in turn, promotes trophotropic processes of the limbic and midbrain area, normalizing the regulatory centers of the hypothalamus, autonomic nervous system, and reticular activating system. The net result of this process of functional normalization through synchrony training is a state of homeostasis facilitating optimal functioning. / Source: Dissertation Abstracts International, Volume: 41-10, Section: B, page: 3927. / Thesis (Ph.D.)--The Florida State University, 1980.

This research was undertaken to satisfy the dearth in the literature relative to clinical biofeedback technique with respect to selected personality types. It was further designed as a means of elucidating interactions between dependent measures in biofeedback training and some of the myriad intervening variables which affect them. This study focused on subjects' acquisition of operant control of frontalis EMG through biofeedback and examined the extent to which a linear dependence exists of performance on instructional set and personality. Sixty college undergraduates were selected for participation in the study. Subjects selected for participation were individuals scoring highest on the Pleasing and Achieving dimensions of the Langenfeld Inventory of Personality Priority (LIPP). The instrument generates a five factor personality profile theoretically based in Adlerian psychology. Subjects learned to reduce frontalis EMG during five 6 minute trials of feedback training subsequent to instructions about the biofeedback task. These instructions were classified as: (a) pleasing instructions believed appetitive to those with high pleasing scores, and (b) achieving instructions believed appetitive to those with high achieving scores. A Semantic Differential List was employed to test for perceived differences in the experimenter by subjects. / The linear dependence of percent change in EMG (performance) on instructional set and LIPP personality score was summarized through the calculation of the multiple regression analysis. No linear relationship was evident between any of the independent variables and performance for the achieving population. For pleasing subjects, however, a strong linear dependence of performance on instructional set and LIPP personality score was revealed (F = 4.183, p < .026). The results further revealed a significant personality priority by instructional set interaction effect with respect to the activity (p < .013) and potency (p < .022) factors depicted by the Semantic Differential List. Achieving-pleasing and pleasing-achieving groups rated the experimenter significantly higher on the potency factor than did the achieving-achieving group (p < .05). / A discussion includes an interpretation of the results and implications for practical and heuristic applications. / Source: Dissertation Abstracts International, Volume: 43-10, Section: B, page: 3400. / Thesis (Ph.D.)--The Florida State University, 1982.

In order to determine which changes in the cortical origins of the corticospinal tract (CST) have taken place along the Anthropoid ancestral lineage, the retrograde tracer, horseradish peroxidase was applied to the hemisected spinal cord of 22 carefully selected mammals. Several morphological features of the cells originating the CST were examined in each animal including the number of cells, their distribution across the cortex, their laminar distribution, area, density, concentration and cell type. / The results indicate that two spatially distinct Regions in the neocortex originate corticospinal axons in each of the animals in the sample. In addition to these two Regions probably common to all Therian mammals, the results indicate that a new source of corticospinal axons probably emerged in the Primate Order. This new CST area is located on the lateral surface of the cortex of Prosimians and New World Anthropoids and is buried in the caudal bank of the inferior arcuate sulcus in Old World Anthropoids. / Several strictly quantitative changes in the corticospinal neurons are also described. These quantitative changes can be subdivided into those that occurred in a pre-Prosimian stage (e.g., increase in number, density and column height) and those that occurred in a post-Prosimian stage (e.g., decrease in density, increase in area of origin of the CST). / Finally, these changes, both qualitative and quantitative are discussed with respect to their correspondence with cytoarchitectonically defined and electrophysiologically defined cortical fields. / Source: Dissertation Abstracts International, Volume: 46-10, Section: B, page: 3631. / Thesis (Ph.D.)--The Florida State University, 1985.