Thesis (Ph. D.)--University of Wisconsin--Madison, 1983. / Typescript. Vita. Includes bibliographical references.

Thesis (M. S.)--Texas A&M University, 2005. / "Major Subject: Veterinary Physiology" Title from author supplied metadata (automated record created on Apr. 27, 2007.) Vita. Abstract. Includes bibliographical references.

Achondroplasia and hypochondroplasia are two forms of skeletal dysplasias caused predominantly by single base mutations in the fibroblast growth factor receptor 3 gene (FGFR-3). The mutation for achondroplasia is a G1138A/C substitution and the mutation for hypochondroplasia (occurring about 50% of the time) is a C1620A/G substitution. Recent genetic studies have shown that spontaneous mutations for achondroplasia and hypochondroplasia occur exclusively on the paternally derived chromosome, suggesting that these mutations occur preferentially during spermatogenesis. For unknown reasons, the mutation rates at these FGFR-3 nucleotides appear to occur at a much higher frequency than nucleotide specific mutation rates observed in other human genetic diseases. The purpose of this study was to develop an assay that could detect the frequencies of achondroplasia and hypochondroplasia causing mutations in human sperm. A Needle-in-a-Haystack PCR/RE/LCR selection technique has been developed that measures single base changes, commonly single base substitution mutations, at sensitivities of one mutant allele in one cell in up to 10⁷ wild-type cells. This technique was modified and designed for the achondroplasia and hypochondroplasia base sites 1138 and 1620 of the FGFR-3 gene. With the development of this technique, future studies could focus on determining the frequencies of the mutations in the sperm of fathers of affected children and the frequencies of the mutations in the sperm of the normal population. These studies will help elucidate the paternal age effect, have important implications in genetic counseling and provide a novel method by which to study genetic disease in humans.

Acute laminitis is a severely debilitating disease of the laminae of the equine digit; however, the mechanism(s) of pathogenesis have yet to be fully elucidated. In physiologic states, the endothelium synthesizes substances, such as nitric oxide (NO; vasodilator) and endothelin-1 (ET-1; profound vasoconstrictor), which play a crucial role in vasomotor regulation. The overall hypothesis is that the initiating factor in the onset of acute laminitis is a disruption in the balance between NO and ET-1, which leads to digital vasoconstriction and subsequent laminar ischemic necrosis. In vitro studies with digital vessels from healthy horses and horses with naturally-acquired laminitis determined that ET-1 caused concentration-dependent, sustained contraction of arteries and more profound contraction of veins, and incubation with the nonselective ET receptor antagonist (PD145065) at a 10-5 M concentration abolished these contractile effects. ET-1 was then administered into the digit of healthy conscious horses, which resulted in reduced blood flow and the ET antagonist, especially in combination with a NO donor, reversed these reductions. Naturally-acquired laminitic horses had a trend for increased jugular and cephalic venous plasma ET-like immunoreactivity, and horses during the development of black walnut extract (BWE)-induced laminitis developed increased digital venous plasma ET-like immunoreactivity. After validation for equine tissues, ET-1 immunohistochemical staining was conducted on digital vascular and laminar tissues, but no notable differences were found between healthy and naturally-acquired or experimentally-induced laminitic horses. During the developmental stages of BWE-induced laminitis, digital blood flow initially decreased followed by hyperemia, corresponding with demonstration of clinical signs of laminitis. Administration of the ET antagonist, and the antagonist combined with a NO donor, improved Starling force alterations by improving digital vascular resistances and blood flow. Utilizing digital vessel rings from BWE-treated horses, ET-1 caused a concentration-dependent contraction in vitro that was abolished by the ET antagonist. Endothelium-dependent vasodilation was decreased in these vessels, demonstrating possible altered endothelial function due to BWE administration. Based on the results of these studies, ET-1 appears to play a role in the pathophysiology of acute laminitis in horses and continued investigations evaluating ET antagonists as preventative and therapeutic agents for this devastating disease are warranted.

Gastrointestinal tract disease is the leading natural cause of death in horses and horses with ischemic intestinal disease have the greatest mortality. We hypothesized there is basal synthesis of endothelin-1 (ET-1) in the intestinal tract of healthy horses that is likely involved in regulating vasomotor tone, secretion and motility and that ET-1 synthesis increases with gastrointestinal tract disease, which may be involved in the pathophysiology of these disorders. Plasma ET-like immunoreactivity was increased in horses with naturally-acquired gastrointestinal disease, compared with normal horses; values were greatest in horses with large intestinal strangulation obstruction, enterocolitis and peritonitis. There was an association between ET-1 levels and survival, PCV and duration of signs of pain. Immunohistochemical staining for ET-1 was present in surface epithelium, villi, muscularis and serosa of numerous intestinal segments in healthy horses. Staining was also present in submucosal vessels with veins staining more intense than arteries. Staining appeared more diffuse and intense in samples from horses with intestinal strangulation obstruction. Polymerase chain reaction analysis revealed the presence of ET-1 gene expression in numerous intestinal segments of normal horses. These findings suggest ET-1 is involved in physiologic functions such as regulation of secretion, vasomotor tone and motility, and that increased ET-1 with strangulation obstruction may be involved in the pathophysiology of these disorders. ET-1 caused sustained, concentration-dependent increases in cecal longitudinal smooth muscle tone in vitro, but the magnitude of contraction was less than that induced by carbachol. Pre-incubation of tissues with ETA (BQ-123) and ETB (IRL-1038) receptor antagonists alone did not inhibit ET-1 induced contraction. However, contractile responses were inhibited when tissues were incubated with both antagonists (10-5 M) together, suggesting both ETA and ETB receptors mediate the contraction. Electric field stimulation did not change the contractile response. These studies indicate a physiologic role of ET-1 in the equine gastrointestinal tract and that increased synthesis and release occurs with gastrointestinal tract disease, especially ischemic conditions, and may contribute to the pathophysiology of these disorders. Further studies involving ET-1 and ET antagonists appear warranted.

Thesis (M.Sc.Agric.(Animal Science))--University of Pretoria, 2002. / Summaries in Afrikaans and English. Includes bibliographical references.

Thesis (doctoral)--Universität Bern, 1960. / Includes bibliographical references.

Anesthesia affects the central nervous system and can suppress cardiovascular activity. In this study, we compared two anesthetics, urethane and alpha-chloralose, to better understand their effect on sympathetic control of blood pressure, as well as how they would affect baroreceptor response and blood pressure in adult rats. To do this we performed baroreceptor tests in adult rats under isoflurane anesthesia and then either urethane (I.V. 1.25 g/kg, n=2) or alpha-chloralose (100 mg/kg, n=2). We found that baroreceptor responses were not significantly different between urethane or alpha-chloralose anesthesia. However, significant depression of baseline blood pressure occurred under alpha-chloralose anesthesia compared with urethane. Additionally, we observed significant elevation of baseline renal sympathetic nerve activity (RSNA) occurred under urethane anesthesia. Ultimately, our findings suggest that both urethane and alpha-chloralose provided sufficient induction of anesthesia without significantly modifying baroreceptor response. However, since urethane significantly raised baseline sympathetic nerve activity, it should be avoided in studies where raised sympathetic activity could confound with the test results. alpha-chloralose significantly lowered baseline blood pressure by nearly 30%, and its use should be avoided in studies where lowered blood pressure may confound the results.

Two studies were conducted to investigate factors involved in absorption of immunoglobulins in the preruminant neonate. In the first study 26 Angus cows were fed 57% or 100% of their NRC recommended requirements for protein and energy for the last third of gestation in each of 2 years. Resulting calves were fed measured amounts of colostrum from their dam or from a cow of the reciprocal nutritional treatment group. Cows from the restricted intake treatment lost weight and body condition (P < .05). Gestation length, birth weight, calving ease, days open end weaning weight, however, were not affected by treatment. Calves born to restricted fed dame had higher serum cortisol and lower serum T₃ concentration (P < .05), but absorption of IgG was not affected. Calves fed colostrum from restricted cows did have lower serum IgG concentrations (P < 0.2); although, none of the calves were considered hypogammaglobunemic. In the second study, 2 trials were conducted to evaluate the effect of varying cortisol concentrations on Ig absorption in lambs. Treatments consisted of control (CO), high cortisol (HC), single peak of cortisol (SP) end low cortisol (LC). Lambs in trial 1 were obtained on d 136 to 138 of gestation by caesarean operation. HC and SP lambs tended to have a faster rate of Ig absorption through 24 h, but did not differ from CO lambs in serum Ig concentration by 36 h. Precocious closure to Ig absorption had occurred for LC lambs by 20 h end they had lower Ig concentrations at 36 and 48 h (P < 0.05). In trial 2, lambs were obtained on d 140 to 142 of gestation. Lambs had a shorter Ig absorptive period than trial 1 (24 vs 36 h for CO]. Premature closure for the LC lambs occurred by 16 h postpartum (P < 0.05) and they tended to have depressed Ig concentrations post 24 h. / Ph. D.

Assisted reproductive technologies developed in domestic cattle serve as a starting point in similar studies on nondomestic bovids. The common eland is a useful model species for studies on rare tragelaphine antelopes. In Chapter 3 of the present study, effects of components/attributes of protein-free embryo culture media on the in vitro development of in vitro-derived bovine embryos were evaluated. A 2 x 2 factorial study comparing effects of groups of amino acids (20aa or 11aa) in two base media (modified KSOM or BM-3) demonstrated that amino acids and base medium affected embryonic development. A subsequent 7 x 2 factorial experiment to evaluate effects of osmotic pressure and supplement type in BM-3-20aa showed that embryonic development was largely affected by supplements and identified glucose (0.2 mM) as a crucial supplement. In Chapter 4, the use of behavioral training and handling of elands in a hydraulic chute to perform transvaginal ultrasound-guided oocyte retrieval without inducing general anesthesia were evaluated. Nine of 10 females associated specific sound cues with food treats. Females varied in their response interval to audio cues and to training for voluntary entry into the chute. Handling elands for oocyte retrieval required sedation and increased blood glucose levels. In Chapter 5, type of estrous synchronization or ovarian stimulation protocol did not affect ovarian response. Animals, but not month of the year, affected ovarian response. In 37 oocyte retrieval procedures using seven females, an average of 12.8 follicles yielded 9.8 oocytes, of which up to 73% matured to metaphase II. In vitro fertilization, intracytoplasmic sperm injection and nuclear transfer resulted in embryonic development. In conclusion, the bovine embryo culture study suggests that the beneficial effects of amino acids are influenced by the base medium and glucose plays more important roles in non-ATP producing pathways. Behavioral training and handling of sedated females in a hydraulic chute is a reliable method for collecting eland oocytes, which can undergo in vitro maturation and some in vitro embryonic development.