• EFFECTS OF SODIUM BICARBONATE ON GLUCOSE HOMEOSTASIS AND BLOOD PRESSURE IN CHRONIC KIDNEY DISEASE

      Mannon, Elinor; Department of Philosophy (Augusta University, 2021-10)
      Sodium bicarbonate (NaHCO3) is a therapeutic used in chronic kidney disease (CKD). NaHCO3 is typically used to treat metabolic acidosis, but clinical studies have indicated that NaHCO3 supplementation may slow CKD progression. As such, NaHCO3 is now given to patients with CKD to slow the decline of glomerular filtration rate. However, the consequences of chronic NaHCO3 supplementation in CKD remain unclear. Acidosis has been associated with insulin resistance, and correction of acidosis with NaHCO3 was reported to improve insulin sensitivity. Our goal in Aim 1 was to determine whether acid and alkali loading would promote loss of acid-base homeostasis and consequently decrease insulin sensitivity. We determined that the blood glucose response to insulin is enhanced following renal mass reduction, and that this response is not reversed by an acidosis. Additionally, the development of an alkalosis did not impair the blood glucose response to insulin. Alkali can promote potassium (K+) wasting, and an association between K+ wasting and insulin resistance has been identified in clinical and basic science research. Our goal in Aim 2 was to identify whether chronic NaHCO3 treatment may promote loss of insulin sensitivity through effects on K+ status. We determined that chronic NaHCO3 treatment impairs insulin sensitivity when combined with other K+ wasting stimuli. K+ deprivation alone also impaired the blood glucose response to insulin, however these impairments in insulin sensitivity were not directly related to decreases in intracellular [K+]. Salt-sensitivity increases as functional renal mass declines, and chronic sodium (Na+) loading with NaHCO3 may contribute to hypertension in patients with CKD. Our goal in Aim 3 was to investigate whether NaHCO3 loading promotes similar levels of Na+ and volume retention, and hypertension as sodium chloride (NaCl) loading does in a rat model of CKD. We found that NaHCO3 was pro-hypertensive, but to a lesser degree than NaCl, despite similar amounts of Na+ and volume retention. From these studies we concluded that NaHCO3 does not improve insulin sensitivity through its effects on acid-base status. Further, access to dietary K+ may improve insulin sensitivity with chronic NaHCO3 treatment. Finally, NaHCO3 can promote hypertension in CKD.
    • Bioactivity and mechanism of action of resveratrol, a polyhenolic phytoalexin, in sickle cell disease

      Agyekum, Davies G.; Medical College of Georgia (Augusta University, 2013-07)
    • Physicians' perceived incentives for association with nurse practitioners in the delivery of primary care

      Adinaro, Denise; School of Nursing (Augusta University, 1980-08)
      The purpose of this study was to identify those factors which physicians , currently associated with nurse practitioners, perceive as incentives in their motivation to associate with these nurse practitioners in providing primary care. A mail survey was sent to nurse practitioners and their associate physicians throughout the State of Georgia, with two follow-up postcard mailings. Data were collected for a 4 week period and a 30.46 return was obtained. A mean ranking of the identified incentives was performed. Two major categories of incentives were identified . To increase the quality of care was considered to be most important and to expand the services offered in general was rated second as incentives for physician association with nurse practitioners.
    • A NOVEL NETWORK BASED LINEAR MODEL FOR ENRICHMENT OF SYNERGISTIC DRUG COMBINATIONS

      Li, Jiaqi; Department of Physiology (Augusta University, 2021-07)
      Drug combination therapies can improve drug efficacy, reduce drug dosage, and overcome drug resistance with respect to cancer treatments. Current research strategies to determine which drug combinations have a synergistic effect rely mainly on clinical or empirical experience and screening predefined pools of drugs. Given the number of possible drug combinations, the speed and scope to find new drug combinations are very limited using these methods. Due to the exponential growth in these combinatorials, it is difficult to test all possible outcomes in the lab. Several large-scale public genomic and phenotypic resources that provide data from single drug-treated cells as well as data from small molecules deliver a wealth of cellular response information. This data gives opportunity to overcome limitations of the current methods. The development of a new strategy for advanced data processing and analysis that includes a computational prediction algorithm is highly desirable. Because of this, a program was written that predicts synergistic drug combinations using gene regulatory network knowledge and an operational module unit (OMU) system generated from single drug genomic and phenotypic data. As a proof of principle, we applied the pipeline to a group of anticancer drugs and demonstrated how the algorithm could help researchers efficiently find possible synergistic drug combinations using single drug data to evaluate all possible drug pairs.
    • Studies on calcium transport of the sarcoplasmic reticulum in skinned cardiac muscle

      Zhu, Yu; Department of Physiology and Endocrinology (Augusta University, 1990-11)
    • Angiogenesis-associated gene expression changes in surgical skin flaps of diabetic rats

      Zhou, Miao Xian (Cindy); Medical College of Georgia (Augusta University, 2010-07)
    • Aquaporin 3 in keratinocyte differentiation

      Zhan, Xiangjian; Medical College of Georgia (Augusta University, 2003-08)
      Aquaporin 3 (AQP3) is a channel that transports both water and glycerol. AQP3- null mutant mice exhibit skin defects, including impairment of water holding capacity, barrier recovery and wound healing and decreased glycerol content. We hypothesized that AQP3 is involved in the regulation ofkeratinocyte proliferation and differentiation and this regulation is mediated, at least in part, by the functional interaction between AQP3 and phospholipase D (PLD). Here we demonstrate that AQP3 expression was down-regulated at the transcriptional level and glycerol uptake was reduced when primary mouse keratinocytes were induced to differentiate. In co-transfection experiments, we found that AQP3 decreased the promoter activity of keratin 5, a keratinocyte proliferation marker, but increased the promoter activity of keratin 10 and involucrin, an early and intermediate keratinocyte differentiation marker respectively. These results suggest that AQP3 is a regulator of early keratinocyte differentiation. In further investigatjons to determine the sigualing function of AQP3 in regulating keratinocyte differentiation, we found using sucrose gradient centrifugation, irnmunoprecipitation analysis, confocal microscopy that AQP3 and PLD2 were colocalized in lipid rafts. In addition, we demonstrated that AQP3 could contribute to the synthesis of phosphatidylglycerol (PG) and that PLD2 was able to utilize glycerol as a substrate to synthesize PG. These data suggest that AQP3 transports glycerol for use as a physiological primary alcohol substrate for-adjacent PLD2 to generate PG. Our results, together with the reports that PG is an activator of protein kinases (PKqm and PKCe) and also contributes to protein-protein interactions in membranes, suggest that glycerol AQP3-PLD2-PG is a potential signaling pathway in regulating keratinocyte differentiation.
    • EFFECTS OF ATTENUATION OF a8 AND a6 INTEGRINS ON THE DEVELOPMENT OF CIDCKEN OPTIC TECTUM

      Zhang, Zhiqiang; Medical College of Georgia (Augusta University, 1997-05)
    • Characterization of leydig cell development in the rat testis

      Zhai, Juan; Medical College of Georgia (Augusta University, 1996-05)
    • The effect of dentin desensitizers on the retention of full crowns cemented with a variety of luting/bonding agents

      Yim, Nantiya Harnkul; Department of Oral Biology (Augusta University, 1999-04-21)
    • Structural and functional aspects of organic cation transporters

      Wu, Xiang; Medical College of Georgia (Augusta University, 1999-07)
    • Confidence interval estimation for a binomial proportion when no successes are observed

      Wimmer, Courtney; Dias, James; Medical College of Georgia (Augusta University, 2009-04)
      Confidence interval estimation for a binomial proportion is a long debated topic, resulting in a wide range of exact and approximate methods. Many of these methods perform quite poorly when the number of observed successes in a sample of size n is zero. In this case, the main objective of the investigator is usually to obtain an upper bound, i.e., the upper limit of a onesided confidence interval. Traditional notions of expected interval length and coverage probability are not applicable in this situation. In this paper we use observed interval length and p-confidence to evaluate nine confidence interval methods for a binomial proportion. We also consider approximate sample sizes needed to achieve various upper bounds near the zero boundary. We show that many popular approximation methods perform poorly based on these criteria and conclude that the-exact method has superior performance in terms of interval length and p-confidence.
    • A Variable prenatal stress paradigm as a valid drug discovery platform for cognitive deficits associatied with neuropsychiatric disorders

      Wilson, Christina Ann; Medical College of Georgia (Augusta University, 2012-10)
      Cognitive dysfunction is now recognized to be central to the functional disability of several neuropsychiatric disorders. However, treatment options for the management of cognitive symptoms are limited and the development of novel therapeutics has been made difficult by the lack of appropriate animal models. It has been suggested that variable prenatal stress (PNS) in rodents might be an etiologically appropriate model for some components of schizophrenia. Thus, the overall goal of this dissertation project was to conduct a comprehensive behavioral study of the model to assess face validity, and to make a preliminary assessment of its construct and predictive validity. Our results indicate that exposure to PNS results in elevated corticosterone levels following exposure to acute stress, increased aggressive behaviors, as well as increased locomotor activity and stereotypic behaviors. Further, PNS rats had altered innate fear responses to predator odor as well as impaired fear extinction. Additionally, PNS in rats was associated with impairments of sustained attention, inhibitory response control, and recognition memory all of which could be attenuated by the norepinephrine reuptake inhibitor, atomoxetine. Collectivity, these data ,support the premise that PNS in rodents is a valid model system for studying some behavioral components of neuropsychiatric disorders as well as their treatment.
    • Interaction of ET-1 with vasoactive mediators

      WIlliams, Jan Michael; Medical College of Georgia (Augusta University, 2005-07)
    • Expression of connexin 43 in orthodontic tooth movement in a rat model

      Whitehead, James D., III; Department of Oral Biology (Augusta University, 1998-12)
    • Relationship between job satisfaction and intent to stay

      West, Myrion J.; School of Nursing (Augusta University, 1993-01)
    • Effect of structured patient education on level of hope in cancer patient

      Wells, Gayle; School of Nursing (Augusta University, 1991-02)
      The purpose of this study was to determine the effect of patient participation in a structured education program on the level of hope in cancer patients. The sample consisted of 34 adult subjects diagnosed with cancer within the last five years. The control group (n = 17) consisted of patients receiving care at a private physician's office. The treatment group (n = 17) consisted of participants in a structured education program (I Can Cope) at three sites in the southeastern United States. The Nowotny Hope Scale (NHS) (Nowotny, 1989) was used to measure.hope. A quasiexperimental non-equivalent control group pretest posttest design was utilized tb test the following hypothesis: Adult cancer patients who attend structured educational classes will score higher on a scale measuring hope than those patients who have not attended such a class. Both groups represent naturally occurring collectives and randomization was not possible. The groups were matched by type of cancer diagnosis. The analysis of covariance (ANCOVA) revealed no significant difference (p = .139) in the adjusted posttest scores of the two groups; therefore, the hypothesis was not supported. In this study, the level of hope for participants in a structured education program did not differ from the level of a similar group not attending such a program. However, in view of the attention given to the concept of hope as a factor in facing the diagnosis of cancer it is important that research efforts continue to be directed to the discovery of effective interventions to foster hope.