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Adaptations of Adipose Tissue Expandability in Gestation are Associated with Maternal Glucose MetabolismRojas-Rodriguez, Raziel 17 July 2019 (has links)
Pregnancy induces maternal metabolic adaptations including mild glucose intolerance and weight gain in order to support fetal development and lactation. Adipose tissue (AT) function in gestation is featured by reduced insulin sensitivity and fat mass accrual which partly accounts for the weight gain in pregnant women and adaptation of glucose metabolism. A common metabolic pregnancy complication is gestational diabetes mellitus (GDM), a disease characterized by impaired glucose tolerance with onset in gestation. However, the relationship between AT expandability and glucose metabolism in gestation is not well understood. The goal of this thesis was to investigate the adaptations of human AT expansion induced by pregnancy, how these changes are reflected in pregnancies complicated with GDM and characterize a mouse model to study the mechanisms underlying this disease. This dissertation illustrates that pregnancy promotes AT expandability by a signaling mechanism between placental pregnancy-associated plasma protein-A (PAPP-A) and AT- insulin-like growth factor binding protein-5 (IGFBP5). In addition, gravidas with GDM showed impaired AT expansion. Studies investigating the relationship between PAPP-A and glycemic state demonstrated that low levels of PAPP-A in the 1sttrimester are highly associated with the development of GDM. Moreover, PAPP-A knockout mice exhibit reduced insulin sensitivity and impaired AT growth exclusively in gestation. These results expand the knowledge of AT biology in gestation and have the potential to improve maternal care by proposing PAPP-A as an early biomarker and possible therapeutic for GDM. It also introduces a new mouse model to study the etiology of gestational diabetes. Read more
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Endothelial Driven Inflammation in Metabolic Disease: A DissertationMatevossian, Anouch 25 February 2015 (has links)
Obesity has been on the rise over the last 30 years, reaching worldwide epidemic proportions. Obesity has been linked to multiple metabolic disorders and co-morbidities such as Type 2 Diabetes Mellitus (T2DM), cardiovascular disease, non-alcoholic steatohepatitis and various cancers. Furthermore, obesity is associated with a chronic state of low-grade inflammation in adipose tissue (AT), and it is thought that insulin resistance (IR) and T2DM is associated with the inflammatory state of AT.
Endothelial cells (ECs) mediate the migration of immune cells into underlying tissues during times of inflammation, including obesity- and cardiovascular disease-associated inflammation. Cytokines and chemoattractants released from inflamed tissues promote EC activation. Upon activation, ECs increase the expression of leukocyte adhesion molecules (LCAMs) including intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), E-selectin (E-sel) and P-selectin (P-sel). Increased expression of these LCAMs and increased infiltration of inflammatory cells such as macrophages, have been linked to IR, diabetes and atherosclerosis in obese individuals. Preliminary data from our lab suggests that lipolysis induced by the β-adrenergic receptor agonist CL 316,243 causes an increase in endothelial LCAM gene expression. In addition, histological analyses show increased content of immune cells within AT after the ECs become activated.
Here, we demonstrate that CL 316,243-induced lipolysis causes infiltration of neutrophils in wild type (WT) but not E-sel knockout (KO) mice. Following EC activation, there was also a marked increase in cytokine gene expression including IL-1β, MCP-1, and TNF-α in an E-sel-dependent manner. In contrast, fasting-induced lipolysis was associated with increased macrophage infiltration into AT in the absence of EC activation in an E-sel-independent manner.
We also examined the role of mitogen activated protein kinase kinase kinase kinase 4 (MAP4K4) as a potential contributor to endothelial activation and atherosclerosis. Here we demonstrate that deletion of MAP4K4 in ECs in vitro diminishes TNF-α-induced EC activation. Additionally, MAP4K4 depletion in primary ECs derived from lungs of mice expressing MAP4K4 shRNA decreases EC activation. Finally, endothelial specific depletion or loss of MAP4K4 reduced atherosclerotic plaque formation in vivo. Taken together, these results highlight the importance of the endothelium in modulating obesity-associated comorbidities. Furthermore, these data implicate endothelial MAP4K4 as a novel regulator of EC activation and consequently AT inflammation and atherosclerosis. Read more
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A Plan for the Implementation and Evaluation of Diet Education in Type 2 DiabetesRamsumeer, Soy 01 January 2016 (has links)
Abstract
Type 2 Diabetes Mellitus (T2DM) is the seventh leading cause of death in the United States with a projected increase of 552 million people worldwide who will be affected with this illness by 2030. The need to address this issue is vital to prevent complications and reduce healthcare spending. The DNP project is aimed at planning and designing a nutritional education program tailored toward specific ethnic groups in order to increase knowledge in making healthy food choices. This project is intended to educate Registered Nurses (RNs) on nutrition so that they can offer dietary knowledge to T2DM patients. Additional patients can be reached by educating the RNs rather than patients being limited to consultations with a Certified Diabetes Educator or Registered Dietician. This project focused on whether healthy nutrition tailored toward the individual's own ethnic foods helps to stabilize glycemic values for patients with Type 2 diabetes. A toolkit was utilized to aid with the RNs' learning on healthy nutrition and its impact on the management of blood glucose. It addressed areas such as food groups and calories, grocery shopping, preparation methods, and portion control. The framework for design utilized the basic concepts associated with the systems theory with an intended goal to prevent further complications and improve patients' glycemic value through consuming nutritious foods. The logic model will be used to evaluate the impact of healthy nutrition on blood glucose through pre- and post-program tests of the RNs' nutritional knowledge on healthy eating. The continuation of this program will promote positive social change by helping patients to achieve a healthier lifestyle and reduce healthcare expenditures. Read more
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Hypothalamic manipulation of the anuran HPG axis: alternative hormones and a non-invasive administration route for amphibian Assisted Reproductive Technologies (ART)Saylor, Erin Michelle 08 December 2023 (has links) (PDF)
Amidst the amphibian extinction crisis, in situ and ex situ amphibian species conservation initiatives utilize assisted reproductive technologies for optimal genetic management of captive and wild populations. Development of effective, simple, low-cost methods for obtaining gametes for artificial fertilization, sperm biobanking, or natural breeding alleviates obstacles for institutions or programs to apply reproductive technologies. Objectives herein include investigating the efficacy of alternative hormones for inducing spermiation, an alternative hormone administration route for inducing ovulation, exploring the physiological effects of hormone therapy, and utilizing sperm from deceased animals for biobanking.
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Determination of a Two-Week `Window’ for PCB Influence on Ultrasonic Vocalization and Other Behavioral Measures in Young Sprague-Dawley RatsBaldwin, Jeffrey W., Jr. 09 July 2014 (has links)
No description available.
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Behaviour and endocrinology of meerkats in zoosScott, Katy January 2014 (has links)
Zoo-based research is important both to inform management decisions on captive animals and because zoos, at their best, provide a naturalistic environment, which it is possible to manipulate, in which scientific research can be performed. Extending research to multiple zoos enables investigation into how variations between zoos impact their occupants. Comparing zoo animals to their wild conspecifics can inform management decisions, improve breeding and reintroduction programmes, educate the visiting public and allow assessment of the relevance of zoo-based research to the broader field. The impact of captivity on social animals is particularly interesting, as they cannot determine their own social environment. Meerkats (Suricata suricatta) are a highly social species of mongoose which have been extensively studied in the wild, and which are common in European zoos; they are therefore an ideal focal species with which to assess the impact of aspects of the zoo environment. This thesis presents a study of the behaviour, endocrinology and morphology of meerkats in ten zoos in the UK and one zoo in Germany. The size of captive meerkats' social groups was found to influence their behaviour and faecal glucocorticoid levels (fGCs), with animals in large groups exhibiting lower fGCs, which supports an optimum group size hypothesis. Meerkats in large groups also spent less time on sentry duty, although a sentry was posted more often in zoos than in the wild, reinforcing the model of state-dependent vigilance. Captive meerkats were found to weigh much more, on average, than their wild conspecifics, with 86.7% of adults more than two standard deviations heavier than the mean weight in the wild. Meerkats in larger enclosures were heavier than those in smaller ones; their weights also correlated with climate, with zoos in cool, dry locations having lighter meerkats. This research did not find that high levels of hormonal stress occur frequently in zoo meerkats, but obesity may pose a health threat to many individuals and its impacts should be a priority for veterinary research. Read more
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INTRINSIC AND EXTRINSIC REGULATION OF PINEAL MELATONIN RHYTHMSLi, Ye 01 January 2016 (has links)
Circadian rhythm is a biological rhythm with period of about 24 hours. Circadian rhythm is universal in phyla from bacteria to mammals and exists in different level from gene expression to behavior. Circadian system consists of three components: 1) a self-sustained oscillator; 2) an input pathway which can alter the phase of the oscillator; and 3) an output such as gene expression, enzyme activity, hormone production, heart rate, body temperature or locomotor activities. The way the oscillator regulates its outputs is complicated, in that on one hand usually the oscillator is not the only factor affecting the outputs, and on the other, the oscillator itself is incorporated in intricate pathways.
Chicken pineal cell culture is a well-established in vitro model to study circadian rhythm. It contains a self-sustained oscillator which can be phase-shifted by light as input and rhythmically releases melatonin as an output. Here I have characterized the role of norepinephrine (NE), the sympathetic regulatory input of pineal gland, and the microenvironment of pineal cells in melatonin rhythmicity of cultured chicken pineal cells. Chapter 1 of this dissertation provides a review of circadian rhythm with a focus on melatonin regulation in pineal gland. Chapter 2 describes the methods to build up a fraction collector which offers high time resolution of sampling for a superfusion system. Chapter 3 is a technical report of a melatonin enzyme-linked immunosorbent assay suitable for high throughput measurement of melatonin. Chapter 4 presents data demonstrating that daily administration of NE recovers damped melatonin rhythm in constant darkness. In addition, NE does not change the expression of clock genes but the recovery effect of NE depends on the internal clock. Furthermore, the data indicates that NE administration stimulates the gene expression of phosphodiesterase 4D (PDE4D) and adenylate cyclase 1 (AC1) in a time order, potentially corresponding to the trough and peak of recovered melatonin rhythm. Chapter 5 presents data showing that the amplitude of melatonin rhythm in cultured pineal cells is affected by microenvironments of the cell culture and connexin plays a role in this effect. Finally, in Chapter 6 I discuss how the results of each chapter demonstrate multiple regulatory mechanism of the melatonin rhythm of chicken pineal cells. Furthermore, I discuss the implications of this work in the field of developmental biology and how the current data will shape future investigations.
My dissertation incorporates engineering, immunocytochemistry, chicken genetics, and biochemical analyses, and will help in better understanding the regulation mechanism of output in a circadian system. Read more
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Integrated testing strategy for the study of the effects of the human pharmaceutical dutasteride on fishMargiotta-Casaluci, Luigi January 2011 (has links)
In recent years, a growing number of human pharmaceuticals have been detected in the aquatic environment, generally at low concentrations (sub-ng/L to low μg/L). These compounds are characterised by highly specific mechanisms of action, high potency and prolonged activity in order to minimise dosing requirements and potential toxicity in patients. Among the various classes of pharmaceuticals, steroids and anti-steroids are widely used, as shown by the analysis of their clinical use carried out at the beginning of this Ph.D. project. Although the amounts used are much lower than the amounts of some other pharmaceuticals (e.g. analgesics), their ability to affect important physiological processes in fish (e.g. reproduction) at very low concentrations (ng/L) suggest that this class of compounds should represent a high priority for ecotoxicological research. In particular, this Ph.D. project addressed the question of whether or not dutasteride, a human pharmaceutical mainly used to treat benign prostatic hyperplasia, may cause adverse effects in the teleost fathead minnow (Pimephales promelas) by inhibiting the activity of both isoforms of 5α-reductase (5αR), the enzyme which convert testosterone into dihydrotestosterone (DHT). The theoretical framework used to guide the design of the experimental studies was based on the combination of several conceptual approaches, including the study of the evolutionary degree of conservation and functionality of the drug target in non-target species, and the cross-species extrapolation of pharmacological and toxicological information generated during pre-clinical and clinical studies in mammals during drug development. The results obtained during the first phase of this Ph.D. project strongly suggested that DHT has a physiological role in the fathead minnow. In fact, 5αRs are evolutionary conserved in this species, 5αRs genes are expressed in tissues such as the testis, and DHT circulates in fathead minnow plasma at concentrations similar to those detected in humans. These findings represented the rationale for testing the effects of dutasteride in the fathead minnow. Dutasteride caused significant adverse effects in all the in vivo studies performed in order to evaluate its potential toxicity on fish, including early life stage and short term reproduction studies, and all the tested life stages were sensitive to the inhibition of 5αRs activity; however, none of the observed adverse effects occurred at concentrations of exposure lower than 32 μg/L (measured concentration). The results also showed that female fish are highly sensitive to disruption of the androgenic pathways, highlighting their utility for the evaluation of potential adverse effects caused by anti-androgens on fish. In conclusion, the results presented in this Thesis suggest that, at present, the potential presence of dutasteride in the environment does not represent a risk to wild fish populations, due to the high concentrations required to elict significant adverse effect (LOEC = 32 μg/L) and the low volume of drug prescribed every year (5.07 kg in UK in 2006). However, the high bioaccumulation factor of dutasteride suggest that further studies should be conducted to elucidate the role played by the bioaccumulation process in the toxicity responses observed in fish. Read more
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THE EFFECTS OF PERINATAL OXYCODONE EXPOSURE ON THE STRESS AXIS AND NEUROBEHAVIORSithisarn, Thitinart 01 January 2017 (has links)
Opiate addiction is now a major public health problem. Pregnant women continue to use opiates during gestation; up to 5.4% of pregnant women report using illicit drugs during pregnancy. Previous studies have shown that perinatal insults and exposure to opiates such as morphine in utero can affect the development of the hypothalamic-pituitary-adrenal (HPA)-axis of the offspring and are associated with higher risk of developing neurobehavioral problems. Oxycodone, a semisynthetic putative kappa opioid receptor and partial mu opioid receptor agonist is now one of the most frequently abused pain killers during pregnancy, however limited data are available regarding whether and how perinatal oxycodone exposure (POE) alters the development and functions of the HPA-axis, the related stress axis and neurobehavioral outcomes of the offspring. Data from these experiments have provided novel evidence that POE indeed is associated with sex-specific changes in the HPA-axis in response to stress that persist beyond the neonatal period. 1) POE is associated with an increased adrenocorticotropic hormone (ACTH) response to corticotropin-releasing hormone (CRH), but not the corticosterone (CORT) response to CRH stimulation in late adolescent male offspring. 2) POE is associated with increased CORT, but not ACTH response to restraint stress test in adult female offspring. These changes in the HPA-axis response to stress may be partially explained by 1) an increase in the subpopulation of CRH neurons that also contain estrogen receptor-beta immunoreactivity following POE which then can exaggerate the stimulation of the HPA-axis, and 2) a decrease in mineralocorticoid receptor-mRNA expression in the hippocampus which may be associated with impaired negative feedback control of the HPA-axis by the limbic system. POE is also associated with cardiovascular changes in response to stress during a classical conditioning paradigm; adolescent male POE rats have a larger blood pressure increase than the control group. Although POE male rats can properly discriminate the stress versus non-stress cues in the conditioning paradigm, they do not retain this memory when retested during adulthood. When tested for learning and memory in a water maze, however, we did not find any differences between control rats and rats exposed to high dose oxycodone in utero. In addition, we demonstrated that exposure to the lower dose of oxycodone in utero is associated with hyperactivity in adult rats when tested in an open field. Our results make a significant contribution to the literature because they extend our knowledge about the effects of oxycodone on the developing brain and the resulting outcomes in animal models that are actually relevant to a current major public health problem in humans and will provide a platform for us to further study the underlying mechanisms and interventions that may mitigate these effects. Read more
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En litteraturstudie om hur kvinnor med diabetes typ 1 upplevde sin sjukdom under graviditetHofflander, Beatrice January 2017 (has links)
Bakgrund: Diabetes Mellitus typ 1 är en autoimmun sjukdom som innebär att kroppens eget immunförsvar förstör insulinproduktionen. Graviditet är en stressituation för kroppen, vilket leder till ökad förbränning och därmed ökat energibehov. Syfte: Syftet med studien var att belysa diabetes typ 1 sjuka kvinnors upplevelser av sin sjukdom i samband med graviditet. Metod: En kvalitativ litteraturstudie baserad på sju vetenskapliga originalartiklar gjordes. Artiklarna kvalitetsgranskades och de artiklar som inkluderades var av hög och medelhög kvalitet. Därefter gjordes analys av materialet med innehållsanalys. Resultat: I resultatet framkom två huvudkategorier; Påverkan av sammanhang och Mötet med vårdpersonal. Slutsats: Det är viktigt att kvinnor med Diabetes Mellitus typ 1 får den kunskap som krävs för att kunna hantera sin graviditet. Kvinnorna upplever dock en kunskapsbrist hos vårdgivarna, både när det rör sig om sjukdomen, men även när det gäller hur graviditeten kan påverka sjukdomen.
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