• Integrated Effects of Leptin in the Forebrain and Hindbrain

      Desai, Bhavna N; Department of Physiology (2014-11)
      Obesity develops because of a sustained positive shift in energy balance. The hormone leptin was identified as a key negative feedback signal in energy balance regulation, yet it has been ineffective in reversing human obesity. Leptin injection studies in experimental animals have identified leptin receptors (ObRb) in the forebrain and hindbrain as critical and independent mediators of leptin responses. We hypothesized that under near physiological conditions; activation of ObRb in both these areas is required to reduce body fat. We used a male Sprague Dawley double cannulation rat model (3rd and 4th ventricle) and infused either saline (S) or sub-threshold doses of leptin (L) for 12 days (0.1μg leptin/24h in 3rd, 0.6μg leptin/24h in 4th) in different combinations SS, SL, LS, LL (3rd-4th), to test for integration of forebrain and hindbrain responses. There was no effect of leptin in single ventricle infused groups (LS, SL) compared to controls (SS). Rats with sub-threshold leptin infusions into both ventricles (LL) showed a 60% reduction in energy intake that reversed after day 6 and a 20% weight loss which stabilized at day 6. Body fat of LL rats was decreased by 30% in 6 days, and 50% after 12 days despite correction of energy intake. LL rats displayed normal activity and maintained normal energy expenditure despite weight loss. We further investigated which brain nuclei are involved in this integrated response using phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) as a marker of ObRb activation and delta FosB (ΔFosB) as a marker of chronic neuronal activation. The weight loss in LL rats was associated with a significant increase in pSTAT3 and ΔFosB within multiple hypothalamic nuclei, including the arcuate, ventromedial and dorsomedial nuclei, with no changes in activation of brainstem nuclei. Our results suggest that under near physiologial conditions, the simultaneous activation of both forebain and hindbrain ObRb is required for leptin to reduce body fat and this is facilitated by leptin in the hindbrain promoting activation of pSTAT3 in the hypothalamus. This provides a new perspective on the physiological role of leptin and could lead to new strategies to treat obesity.
    • The interaction of polycyclic hydrocarbons with nuclear macromolecules

      Vaught, Jimmie Barton; Department of Cell and Molecular Biology (1976-10)
    • An Interdisciplinary Team Approach to Decision-making About the Use of Psychotropic Medication for Individuals with Mental Retardation

      Natvig, Deborah A.; Department of Biobehavioral Nursing (1993-05)
      The purpose of this study was to examine a decision-making model for developing psychotropic medication plans for individuals w ith mental retardation. The study examined relationships among medication knowledge, acceptance of the interdisciplinary team (IDT) process, leadership, consensus, and the quality of the psychotropic medication plan. The study w as conceptualized using Henderson's Model for Nursing. Henderson (19 6 6 ) identified the nurse as an active participant on the IDT who helps plan and implement care designed to m eet the needs of the individual. T w o hundred eight (N = 208) team members from 4 9 interdisciplinary psychotropic medication review teams participated in th e study. Team s from all four large regional Intermediate Care Facilities for the M entally Retarded (ICFs/MR) in one southeastern state participated. Multiple regression and hierarchical multiple regression analyses were performed to test the hypotheses. The first hypothesis, that consensus would be predicted by medication knowledge, acceptance of the IDT process, and leadership w as partially supported. Leadership w as a significant predictor of consensus. The second hypothesis, that the quality of the psychotropic medication plan would be predicted by medication knowledge, acceptance of the IDT process, and leadership was not supported. The third hypothesis, which added consensus to the model, did not explain any additional variance in the quality of the psychotropic medication plan. As part of this study, The Psychotropic Review for Interdisciplinary Decisions and Evaluation (PRIDE) scale w as developed to assess the quality of psychotropic medication plans. Several threats to statistical conclusion validity were identified, which may have Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. affected the results of the study. These included: small sample size, lack of independence of teams, low variability of responses to instruments, and multicollinearity. Psychotropic medication plans from some ICFs/MR were superior to those produced by others. Characteristics of the ICFs/MR, such as, the amount of guidance given to teams through written guidelines and policy, and the degree of administrative support reflected through availability of staff to participate in the review process, may have been the most significant factors influencing the quality of psychotropic medication plan produced.
    • Invasion of gingival tissues by bacteria in healthy and diseased states

      Silverstien, Lee Howard; Department of Oral Biology (1988-05)
    • Investigating Student and Faculty Perspectives Related to Predictors of Success: BSN Curriculum and NCLEX-RN Outcomes

      Cosper, Sharon M; Department of Advanced Studies and Innovation (Augusta University, 5/22/2018)
      The literature reports higher patient satisfaction when care is delivered from baccalaureate-prepared nurses (BSN); however, there is a significant shortage of BSN prepared nurses in the country (Schmidt & MacWilliams, 2015; Roa, Shipman, Hooten, & Carter, 2011). For institutions across the nation, there is a lack of understanding as to why certain students struggle academically throughout the program and on the board certification exam. In order to facilitate training, graduation, and success with NCLEX-RN outcomes for these critical healthcare providers, consideration for why students struggle with curriculum and passing the board certification examination is needed. This study utilized a concurrent embedded mixed methods design to gain a greater understanding as to what factors may be contributing to student difficulty. Participants included graduates (n = 75) and faculty (n = 25) within the College of Nursing in a university located in the southeast region of the United States. Data were collected through review of student records, survey responses, focus group participation, and use of the EQ-i 2.0 for descriptive purposes. Results indicate that the BSN GPA, HESI examination scores, and Adult Health II course grades were found to predict performance on the NCLEX-RN. The qualitative findings illuminate categories of external and interpersonal factors contributing to students’ success and first time pass rates on the NCLEX-RN. The themes of Curriculum, Test Methodologies and Preparation, Teaching and Instruction, Balance, Drive, Compassion and Respect, and Critical Thinking were all relevant for consideration to help nursing programs improve the first time pass rates of their graduates on the NCLEX-RN. Further research utilizing methods to understand emotional intelligence and implications for admission as well as successful outcomes on the NCLEX-RN are indicated based on the qualitative findings of this investigation.
    • Investigating Student and Faculty Perspectives Related to Predictors of Success: BSN Curriculum and NCLEX-RN Outcomes

      Callan, Richard S.; Department of Advanced Studies and Innovation (Augusta University, 5/22/2018)
      The literature reports higher patient satisfaction when care is delivered from baccalaureate-prepared nurses (BSN); however, there is a significant shortage of BSN prepared nurses in the country (Schmidt & MacWilliams, 2015; Roa, Shipman, Hooten, & Carter, 2011). For institutions across the nation, there is a lack of understanding as to why certain students struggle academically throughout the program and on the board certification exam. In order to facilitate training, graduation, and success with NCLEX-RN outcomes for these critical healthcare providers, consideration for why students struggle with curriculum and passing the board certification examination is needed. This study utilized a concurrent embedded mixed methods design to gain a greater understanding as to what factors may be contributing to student difficulty. Participants included graduates (n = 75) and faculty (n = 25) within the College of Nursing in a university located in the southeast region of the United States. Data were collected through review of student records, survey responses, focus group participation, and use of the EQ-i 2.0 for descriptive purposes. Results indicate that the BSN GPA, HESI examination scores, and Adult Health II course grades were found to predict performance on the NCLEX-RN. The qualitative findings illuminate categories of external and interpersonal factors contributing to students’ success and first time pass rates on the NCLEX-RN. The themes of Curriculum, Test Methodologies and Preparation, Teaching and Instruction, Balance, Drive, Compassion and Respect, and Critical Thinking were all relevant for consideration to help nursing programs improve the first time pass rates of their graduates on the NCLEX-RN. Further research utilizing methods to understand emotional intelligence and implications for admission as well as successful outcomes on the NCLEX-RN are indicated based on the qualitative findings of this investigation.
    • Investigating the Role of the Hdac3 Co-Repressor Complex in Glucocorticoid Signaling-Mediated Bone Marrow Lipid Storage with Age

      Pierce, Jessica Liane; Biomedical Sciences (Augusta University, 2019-12)
      Aging bone is characterized by loss of tissue density, marrow fat accumulation, and dysregulated bone marrow stromal cell (BMSC) differentiation. The contribution of the epigenetic regulator histone deactylase 3 (Hdac3) is of increasing interest in bone biology. Hdac3 expression decreases with aging, and the current model for conditional deletion of Hdac3 in Osterix-expressing osteoprogenitor cells (Hdac3-CKOOsx) exhibited an aged bone phenotype in young mice along with the novel finding of osteoblastic (Runx2+ osteogenic cells) lipid droplet storage. In addition, bone-specific loss of Hdac3 activity increases expression of the glucocorticoid (GC)-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (Hsd11b1), suggesting a mechanism for the increased lipid accumulation in aged and Hdac3-deficient BMSC-derived osteoblasts. The cofactor nuclear receptor corepressor 1 (NCoR1), which mediates Hdac3 enzymatic activity in a co-repressor complex (CRC), was proposed as a regulator of Hdac3 activity in bone. Both Hdac3 and NCoR1 expression decreased in aged osteoblasts, and the two factors exhibited synergy in downregulating the promoter activity of glucocorticoid-responsive elements. Because of the relationship between increased GC signaling and osteoporosis, the glucocorticoid receptor (GR) was investigated as a mediator of the marrow fat phenotype, with the hypothesis that loss of GR function in bone would be protective against common forms of osteoporosis. Chronic caloric restriction in WT and GR-deficient (GR-CKOOsx) mice was used as a short-term stressor to induce an osteoporotic phenotype, while aging of GR-deficient mice (where Hdac3 CRC expression naturally decreases) was used as a biologically-relevant model for dual loss of Hdac3 and the GR. Surprisingly, the loss of GR function in osteoprogenitors exacerbated bone loss and marrow fat accumulation in both models—and induced a chronic stress phenotype by increasing cellular bioenergetics and whole-body metabolic rate—providing evidence of a role for the GR in facilitating healthy bone maintenance as well as evidence for compensatory mechanisms that regulate bone biology through GC signaling. GR-deficient bone also induced changes to whole-body physiology (e.g., sarcopenia, decreased physical activity, metabolic dysfunction) that further demonstrate the intricacies of bone as an endocrine organ. The current study provides new avenues to investigate cell signaling, bioenergetics, and tissue crosstalk in osteoporotic bone.
    • Investigation of Rabbit Eye Anterior Segment Reducing Capacity: Interplay Between Hydrogen peroxide, Ascorbic Acid and Reductive Enzyme Systems

      Csukas, Stephen; Department of Endocrinology (1987-06)
      Investigation of -'Rabbit Ey.e. Anterior Segment_ Reducing Capacity: Interplay Between Hydro·gen Peroxide, _Ascorbic Acid. and Reduc~ive Enzyme Systems (Under the Direction of KEITH- GREEN, Ph.D., D.Sc.) The experiments perfo~ed in this' body of work lay the. foundation. •. . for· describing the- sequelae_ .of an in vivo modification in. the reducing · ca.pacity. of the normal rabbit ocular ntilieu following the intro.ductiO? of an oxidative insult into the anterio·r- chamber .. of th~ rabbit eye. The· concentration of intracame:rally ·injected hydrogeri: peroxi-de (HP),. strong en~ugh to c·ause oxidative d~mage, ·and y~t not elicit a white cell response was first determined. The morp~ological and physiological responses to this. ·dose of HP were studied_ ·and described.~ · . - . Age related differences in response· to HP inj e_ction were manifested - ' - . between young and adult rabl:?its •.. Catala-se levels· were measured i~- i:r:i.s ~ ·. ciliary body, _cor~eal endothel-fum, liver ·and- lung. tfssues. Catalase · levels· ·were· demonstrated· to decrease with maturation. Values for ascorbate and HP in· aqueous-humor, an4 ascorbate ·in pla~ma were determined. ·.Ascorbate and HP levels. correlated in young and :adult anitnals •. -Corneal endothelia_l glutathione ·-redox state· ~as .. shifted . toward ·the heavily oxid:i.ze_d $tate ·.a.ftfiar_ intracameral hydrogen· peroxide . . . injectio? confirming 'that the· capacity for HP reduction of the_ . glutathione redox system wit~in the endothelium was being overwhelmed by-· the bolus. HP injection. ·Catalase levels were chemically inhibited by intravenous injection ·of· 3-aminotriazole (3AT) into adult ·animals to mimic the ·condition of a X diminished .ocular-· r~ducing _power. The dose_ response relationship was determined between the dose· ;of 3AT ·and the resultant catalase activ:i,tie~. : ... . . in ocular tissues. · The t~ Jo.r loss of HP from the aqueous humor was determined under control and.catalase inhibited-conditions,· and . ' demonstrated. a trend of fnGreasing length concurrent to increased catalase inhibition. The relationship between 'total ocular· reducing· power and.the t~ of,HP dissipation was determined by combining data ·from . . . . - the two experiments. Ocular. tissues exposed· to intracamerally injected I HPwhile· under 3AT inhibition of catalase activity demonstrated an exacerbated response compared with non-3AT treated· t:j_ssues •. These ' 'results suggest. 'an underlyin'g· r:elationship _between ~otal ocular reducing ' power and exte~t.of damag~ arising from contact with oxidants. 3AT was given orally ~o adult rabbits to determine _the .effects of long term-inhibition of catalase levels. These.animals were not . ' challenged. with in.tracamerally intro<iuced HP but rather were studied· to . ' ·determin~ the effects of 3AT on .endogenous.HP levels. Decreases were noted in levels· of qcular· ascorbate.· and HP but not in levels of plasma ascorbate. Concurrent morphological changes were also rioted in the- .posterior portion of the rabbit lens. These inclqded bleb bing and · · macuolization of· lens fibers~. The findings of thes·e studies witk rabbits suggest that: 1) . ' . catalase-activity decreases with_ maturation: in rabbits; 2) decreases in catalase activity can beachieved using 3AT; 3) challenging oculaJ; tissues with exogenous HP can expose the underlying relationship .. between .ocular reducing power _and· levels of oxidants under normal· conditions and during inflammatory .condi:tions; 4) und·er conditions of greater than· 50% inhibition of catalase levels, other reductive .systems such. as the glutathione redox cycle play. an increasingly important role; and 5) when catalase levels are inhibited for long periods of time without concurrent exogenous HP challenge, major morphological and chemical changes occur in the aqueous humor.
    • An Investigation of the Executive Use of Visual Aids in Teaching Illiterate Chemotherapy Clients

      Clay, Pamela; Department of Nursing (1981-06)
      The purpose of this study was to determine if there was a significant difference in learning comprehension among those illiterate cancer clients who had extensive use of visual aids implemented into their patient teaching program as compared to their counterparts whose patient teaching, contained little or no use of vis·ual aids. This study was limited to a city hospital tumor clinic and the clients therein. Two groups of five subjects each, w~re selected from the above population. Each subject was a cancer client receiving chemotherapy, each was totAlly or functionally illiterate, each was twenty-five years or older, and each had less than an eighth grade education. The control group was given chemotherapy patient teaching utilizing the chemotherapy booklet used routinely in the tumor- clinic.: This booklet required that the patient have the skills to read a:nd ~omprehend •. The exp·erimental group was taught utilizing a newly: developed l chemotherapy booklet created by Clay. This bookle~ contained pictures as its primary mode of communication. The use of posters·, i pictures, and physical objects were also incorporated into their · teaching program. Data were collected using a p_ret.est-po.sttest instrument developed specifically for this study by Clay.
    • Investigation of the mechanism of phenotypic switching in the CYP17 gene in cultured bovine adrenocortical cells

      Deepak, Lala Sukhdev; Department of Biochemistry & Molecular Biology (1991-12)
    • Involvement of arginase upregulation in diabetes- and angiotensin II-induced vascular dysfunction

      Bhatta, Anil; Department of Pharmacology and Toxicology (2015)
      Cardiovascular disease (CVD) is the number 1 killer of men and women in the United States and the world. Diabetes, hypertension, obesity, and aging are some of the risk factors for CVD. A major cause of morbidity and mortality in CVD is vascular dysfunction, which progresses rapidly as the risk factors progress. Vascular dysfunction is characterized by a constellation of blood flow reducing pathologies, including impaired vasorelaxation and elevated arterial stiffening. The mechanisms leading to these vascular abnormalities are not well understood. We tested the hypothesis that arginase, an enzyme in the urea cycle, mediates vascular dysfunction in hypertension and obesity related diabetes. Arginase (ARG) can compete with nitric oxide (NO) synthase for their common substrate, L-arginine. Increased arginase can also provide more ornithine for synthesis of polyamines via ornithine decarboxylase (ODC) and proline/collagen via ornithine aminotransferase (OAT), leading to vascular cell proliferation and collagen formation, respectively. We hypothesized that elevated arginase activity is involved in Ang II-induced vascular dysfunction and that limiting its activity can prevent these changes. We tested this by studies in C57BL/6J mice lacking one copy of the ARG1 gene that were treated with Ang II (1 mg/kg/day, 4 weeks). We demonstrated that Ang II induces smooth muscle cell proliferation, collagen synthesis, and arterial fibrosis and stiffness via a mechanism involving increased arginase activity. Furthermore, we examined the role of arginase in vascular dysfunctions and pathologies associated with obesity-related type 2 diabetes in mice fed with high-fat/high-sucrose (HFHS) diet for 6 months. This model produced a clinical presentation and pathophysiological relevance to the human condition in obesity related type 2 diabetes. We demonstrated that HFHS diet impaired endothelial dependent vasorelaxation and increased arterial stiffness in WT mice, but not in mice treated with arginase inhibitor ABH. Endothelial cell specific knockout of ARG1 (EC-A1-/-) in mice also prevented HFHS induced vascular dysfunctions. Aortic perivascular collagen deposition was significantly higher in HFHS mice compared to normal diet. Furthermore, marked increase in vascular cell adhesion molecule expression and macrophage infiltration into the aortic walls was observed with HFHS diet. Additionally, plasma lipid peroxidase activity, a measure of systemic oxidative stress, was also markedly increased in HFHS mice. These changes were prevented in ABH treated mice and EC-A1-/- mice. These studies suggest that enhanced ARG1 activity promotes vascular dysfunctions associated with elevated Ang II levels or obesity related diabetes.
    • Involvement of calpain in angiotensin II-induced aldosterone production in adrenal glomerulosa cells

      Seremwe, Mutsa P.; Department of Physiology (2014-03)
      Aldosterone is a steroid hormone important in the regulation of blood pressure. Aberrant production of aldosterone results in the development and progression of diseases such as hypertension, cardiofibrosis and congestive heart failure; therefore, a complete understanding of this process is important for developing more effective treatment strategies. Angiotensin II (AngII) regulates aldosterone production, in part through its ability to increase intracellular calcium levels. Calcium can activate calpains, proteases classified as typical or atypical based on the presence of absence of penta-EF-hands. Caplains are involved in various cellular responses which include actin cytoskeletal remodeling and AngII/AT1R signaling. We hypothesized that calpain, in particular calpain 10, is activated by angiotensin II in adrenal glomerulosa cells and underlies increased aldosterone production. We conducted our experiments in two different adrenal glomerulosa cell models: primary bovine zona glomerulosa (zG) cells and human adrenocortical carcinoma cells (HAC15). Our results showed that the pain-calpain inhibitors, calpeptin and MDL 28170, inhibited AngII-induced aldosterone production and CYP11B2 expression in these cells, in addition, AngII-induced aldosterone production and CYP11B2 expression in these cells, in addition, AngII-induced aldosterone production and CYP11B2 expression in these cells, in addition, AngII induced calpain activation in HAC15 cells. The typical (classical) calpain inhibitors PD-150606 and calpastatin peptide had no effect on AngII-elicited aldosterone production, suggesting a lack of involvement of a classical calpain in this process. Atypical calpains expressed by HAC15 cells include calpain 5, 7, 10, 15. The calpain-10 inhibitor, CYGAK inhibited both AngII-induced aldosterone production and CYP11B2 expression. Consistent with this result, knockdown of calpain 10 by an RNA interference technique inhibited aldosterone production and CYP11B2 expression. On the contrary overexpression of calpain-10 using adenoviral infection induced an increase in aldosterone production in the presence and absence of AngII. Our results indicate that AngII-induced activation of calpain 10 in adrenal glomerulosa cells underlies aldosterone production. Our results identify calpain-10 as a potential target for the development of drug therapies to inhibit aldosterone production for the treatment of hypertension.
    • Iontophoresis of thymine arabinoside and other antiviral agents for herpes simplex virus lesions

      WIggens, Carol Ann; Department of Cell and Molecular Biology (1979-07)
    • Iontophoretic Application of Antiviral Agents in Laboratory Animals

      Park, No Hee; Department of Pharmacology & Toxiology (1978-06-05)
    • Isolation and characterization of a lysogenic strain of nocardia erythropolis

      Crockett, Jennifer K; Department of Cell and Molecular Biology (1972-04)