Thesis (PH.D.)--Syracuse University, 2003. / "Publication number AAT 3081631."

Thesis (PH.D.)--Syracuse University, 2003. / "Publication number AAT 3113236."

Thesis (Ph. D.)--Syracuse University, 2005. / "Publication number AAT 3176980."

Thesis (Ph. D.)--Syracuse University, 2005. / "Publication number AAT 3176986."

Hypoluteoidism in the bitch is described as a reproductive condition in which insufficient levels of endogenous progesterone are present resulting in failure to maintain a functional secretory endometrium. This condition can prevent normal embryo implantation, development, and ultimately end in pregnancy loss. Hypoluteoidism in the bitch is a rising concern in small animal theriogenology and current medical therapies available to veterinarians are limited. The aim of this study was to determine the pharmacokinetics (PK) of intravaginally (Crinone®, Serono Laboratories, Norwell, MA) and orally delivered micronized progesterone (Prometrium®, Solvay Pharmaceuticals, Inc., Marietta, GA) in the bitch. We hypothesized that both vaginal and oral treatments would result in a dose-dependent increase in concentrations of plasma progesterone. We further hypothesized that oral dosing of micronized progesterone would result in greater, sustained plasma progesterone than those recorded in bitches treated with intravaginal (IVa) micronized progesterone gel. Eight adult sexually intact bitches in anestrus were arranged in a 4x4 Latin square cross over experimental design. Each subject rotated through four different progesterone treatment groups with a minimum seven day-wash out period between treatments: 100 mg oral micronized progesterone, 200 mg oral micronized progesterone, 45 mg intravaginal micronized progesterone and 90 mg intravaginal micronized progesterone. Blood samples from each subject were obtained at time points 0, 0.5, 2, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours following one initial dosing of each treatment. Concentrations of plasma progesterone were determined by RIA (ImmuChem Double Antibody, 125I RIA Kit, MP Biomedicals, Costa Mesa, CA). Pharmacokinetic analysis was carried out using commercially available software (Phoenix WinNonlin 6.4, Certara Inc., Princeton, NJ). One-compartmental (intravaginal) and non-compartmental (oral administration) modeling were performed to analyze data using the mean concentrations for each dosing to calculate the area under the curve (AUC), maximum plasma concentration (Cmax), time elapsed to reach Cmax (Tmax), and elimination half-life ( t1/2). Results for the 100 mg and 200 mg oral doses and 45 mg and 90 mg IVA doses were as follows: AUC, 30.86, 187.96, 90.64, and 226.68 ng.h.mL-1, respectively; Cmax, 13.47, 169, 8.68, and 13.24 ng.mL-1, respectively; Tmax, 0.5, 0.5, 0.84, and 1.67 hr, respectively, and half-life, 5.87, 6.76, 6.6, and 10.65 hr, respectively. Micronized progesterone was readily absorbed in bitches when administered either orally or intravaginally. Contrary to our initial hypothesis, micronized progesterone exposure over time, as indicated by the area under the curve, was greater when intravaginal micronized progesterone was used. The ability of intravaginal preparations of micronized progesterone to induce sustained progesterone exposure may provide an alternative strategy for treating pregnant dogs whenever hypoluteoidism is being suspected.

Pythium insidiosum is an aquatic oomycete that causes invasive, progressive granulomatous lesions of the skin in dogs, horses, and cats, and of the gastrointestinal tract in dogs. Quantitation of anti-P. insidiosum IgG antibodies can be used in dogs to both confirm a suspected diagnosis and to monitor response to therapy. Recently, an immunotherapeutic product (IP) has been marketed for the treatment of pythiosis in dogs, horses, and people. The aim of this study was to evaluate the effect of administration of this product on anti-P. insidiosum IgG concentrations in dogs. The IP was administered to seven, healthy hound mixes on days zero, seven and 21. Serum was collected on days zero, seven, 14, 21, 28, 35, 42, 49, and 56. Anti-P. insidiosum antibody concentrations were measured using a previously-described ELISA that utilizes a soluble mycelial-based antigen, with results reported as percent positivity (PP) in comparison to a strong positive control serum. Prior to immunotherapy administration, average PP was 7.45% +/- 3.02%. Following immunotherapy administration, there was no significant change in anti-P. insidiosum antibody concentrations, with PP values in all dogs remaining within the range expected for healthy dogs (3% - 15%) for the entire study period. In conclusion, the IP did not produce a significant change in anti-P. insidiosum IgG concentrations when administered to healthy dogs using the protocol suggested by the manufacturers. Further investigation will be required to determine whether a similar effect is observed in naturally infected dogs.

In male hamsters mating behavior is dependent on sufficient androgens and chemosensory input from the main olfactory and vomeronasal systems, whose central pathways contain cell bodies and fibers of gonadotropin-releasing hormone (GnRH) neurons. Regions of the medial amygdala (vomeronasal amygdala) contain androgen receptors and differentially process chemosignals with different social implications. According to published reports of "categorical" patterns of response, conspecific chemosensory stimuli activate the anterior (MeA) and posterior (MeP) medial amygdala, while heterospecific stimuli only activate MeA, in male hamsters (and male mice). Furthermore, chemosignals with distinct social implications differentially activate the dorsal and ventral subregions of MeA and MeP (MeAd/v, MePd/v). In sexually-naïve male hamsters, lesions of the vomeronasal organ (VNX), but not the main olfactory bulb, impair mating behavior. Intracerebroventricular (icv)-GnRH restores mating in sexually-naïve VNX males and enhances medial amygdala (Me) activation by chemosensory stimulation. In sexually-experienced males, VNX does not impair mating and icv-GnRH suppresses Me activation. Thus, main olfactory input is sufficient for mating in experienced- but not naïve-VNX males. I tested whether GnRH enhances access of main olfactory input to the amygdala using icv-GnRH and either electrical or pharmacological stimulation of the main olfactory bulb (MOB), and then examined immediate early gene (IEG) expression there. Electrical stimulation of the MOB did not significantly activate the ipsilateral main olfactory cortex or amygdala in intact or VNX animals. When the IEG counts from both sides of the brain were averaged together, GnRH appeared to enhance activation in the medial amygdala in naïve-intact males, but appeared to decrease activation in naïve-VNX males. I concluded that electrical stimulation was not a sufficient means of driving main olfactory input to downstream brain regions, possibly due to activation of intra-bulbar inhibitory circuits. To alleviate this possible confound, I pharmacologically stimulated the MOB with a mixture of bicuculline methiodide and d,l Homocysteic acid. In sexually-naïve intact-males, MOB stimulation produced significant activation in MeAv and MePv. MePv activation is also characteristic of chemosensory stimuli from potential competitors and predators. In sexually-naïve VNX-males, in which GnRH facilitates mating, GnRH enhanced activation by MOB stimulation in posterodorsal medial amygdala (MePd), a region known to be rich in androgen resceptors and activated by conspecific reproductive chemosignals. Conversely, in sexually-experienced VNX-males, animals that do not require exogenous GnRH to mate normally after VNX, there is a depression in activation in MePd due to GnRH and stimulation in MePd, similar to its response to natural chemosensory stimulation. There also appeared to be a possible effect of VNX due to the difference in selective activation of GnRH in naïve-intact vs. naïve-VNX animals. MeP is also rich in steroid receptors and many chemosensory behaviors are steroid dependent. Therefore, I also tested the activation of androgen receptor (AR)-containing cells in Me after conspecific or heterospecific chemosensory stimulation. Conspecific and heterospecific chemosensory stimuli significantly activated AR-containing cells in Me and significantly increased the number of AR-positive cells in Me above control. The increase in the number of AR-ir cells produced by conspecific stimuli was also significantly above the numbers of AR-ir cells produced by the heterospecific stimulus. These effects may be due to increases of testosterone in response to chemosignals or circuit activity dependent on steroid levels. Future studies on castrated testosterone-replaced males will test these possibilities. The studies of this dissertation provide important information about the neurohormonal regulation of chemosensory and olfactory input to the medial amygdala. The integration of hormonal and chemosensory factors is vital to mating and other social behaviors, and thus species survival. The amygdala is crucial to this process in many vertebrate species, including the hamsters, which use chemicals to communicate with one another. This dissertation suggests, and provides some evidence for a part of the mechanism by which the amygdala accomplishes this integration. / A Dissertation submitted to the Department of Biological Science in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester, 2009. / December 9, 2008. / Olfactory Bulb, GnRH, Androgen Receptor, Vomeronasal, Hamster, Amygdala / Includes bibliographical references. / Michael Meredith, Professor Directing Dissertation; Jon Maner, Outside Committee Member; P. Bryant Chase, Committee Member; Richard Hyson, Committee Member; Zuoxin Wang, Committee Member.

Purpose: To examine pulse oximetry (PO) levels in healthy adult subjects across the adult age span, and to examine the same in a sample of individuals with severe and very severe chronic obstructive pulmonary disease (COPD), and to compare their results. Method: PO levels were recorded via the BIOPAC Systems, Inc. (Goleta, CA) computer based data acquisition unit in conjunction with the Acqknowledge version 4.1 software. Subjects for this study were drawn from a sample of 60 healthy young men and women between the ages of 18 to 38 (30 males and 30 females) and a sample of 60 healthy older men and women (30 males and 30 females) aged 60 years and over. A clinical population of 11 COPD subjects (3 males, 8 females) with an age range of 43 to 82 also participated in the study. Each subject swallowed 10 ml of water three times, 10 ml of applesauce three times, and three small individual pieces of diced pears three times. Results: In the healthy adult group, a 2 (age) x 2 (gender) repeated-measures ANOVA revealed no statistically significant main effects for within-subject factors of bolus type or the interactions of bolus x gender, bolus x age or bolus x gender x age. For between-subject variables there was no main effect for gender but age was significant F(1, 116) = 36.94, p < .001 and the interaction of gender x age was significant F(1, 116) = 5.62, p = .019. For the COPD sample, a Friedman test did not reveal statistically significant differences across the bolus types. For the comparison between the healthy adults and COPD groups a Mann Whitney U test revealed that there were statistically significant differences between the groups for all the of the bolus types: U = 22, p = .011 for water, U = 26, p = .023 for applesauce, and U = 22, p = .011 for pears. Conclusions: Our study contributed information regarding the invariant nature of PO levels in healthy adult swallows across a range of consistencies (for a typical bolus volume). The same pattern was true for individuals with COPD. These results suggest that fluctuations in PO values might indicate respiratory compromise, though additional investigation is warranted to confirm this hypothesis. / A Dissertation submitted to the School of Communication Science and Disorders in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Fall Semester, 2014. / October 24, 2014. / Chronic Obstructive Pulmonary Disease (COPD), Clinical Swallowing Evaulation, Dysphagia, Normal and Abnormal Swallowing, Oxygen Desaturation, Pulse Oximetry / Includes bibliographical references. / Julie A. G. Stierwalt, Professor Directing Dissertation; Leonard L. LaPointe, Committee Member; Richard J. Morris, Committee Member.

Previous research suggests that strict rest following a concussion may prolong symptom presentation, but rest is still one of the most common treatments. Aerobic exercise has effectively reduced symptom burden and exercise intolerance in patients experiencing persistent symptoms longer than 30 days; however, treatment outcomes with sub-acutely concussed patients have not been described. PURPOSE: The purpose of this study was to (1) demonstrate the systemic dysfunction following a sport-related concussion; and (2) examine the safety and efficacy of a 20-minute, low- or moderate-intensity (40% or 60% of HRMAX) controlled treadmill aerobic exercise as a therapeutic modality to improve cardioautonomic, neurological, and psychological function. METHODS: Thirty participants [16.0 ± 1.3 years; 19 sport-related concussed (SRC) and 11 healthy, non-concussed (NC)] were assigned to one of three treatments [1) 40% Age-Predicted HRMAX; 2) 60% Age-Predicted HRMAX; or 3) seated rest using a randomized double block design. SRC participants were evaluated between Day 3-7 of their injury and performed the treatment on the same day. Serial monitoring was performed at rest, during the acute bout of exercise, and recovery. The SRC participants were tracked until clinical recovery. RESULTS: Demographic variables were no different across groups. Autonomic function was not different across groups. Diastolic blood pressure and mean arterial pressure were significantly higher in the SRC participants. A greater percentage of exercising SRC participants improved on measures of ocular motor and vestibular function and symptom reporting compared to the resting SRC participants. 100% of the 40% HRMAX SRC participants and 86% of the 60% HRMAX SRC participants completed the session. Student-athletes who were prescribed exercise following their initial visit reported approximately five days faster than those who were prescribed rest in a previous clinical dataset. CONCLUSIONS: The 40% treatment reported 100% completion rates while both the 40% and 60% groups improved symptoms. Future studies should seek to examine middle school, collegiate, and professional athletes as well as non-athlete populations. / A Dissertation submitted to the Department of Nutrition, Food and Exercise Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester 2019. / March 28, 2019. / active rehabilitation, aerobic exercise, recovery, sport-related concussion, sub-acute, therapeutic exercise / Includes bibliographical references. / Jeong-Su Kim, Professor Directing Dissertation; Cathy W. Levenson, University Representative; Lynn B. Panton, Committee Member; Michael J. Ormsbee, Committee Member; Scott O. Burkhart, Committee Member.

Interleukin-7 (IL-7) is an essential lymphocyte growth factor required for the survival and proliferation of mature T-cells. As a therapeutic agent, IL-7 has the potential to restore T-cell numbers following immune depletion and to promote immunity against cancers. While the survival function of IL-7 is well established, less is known about how it supports T-cell expansion, a critical feature of the immune response. To study the biological effects of IL-7 on T-cell growth, we developed an in vitro culture technique to expand T-cells ex vivo. A significant finding from our studies is that IL-7 did not induce the expansion of all T-cells, indicating that there are inherent differences in the response of individual T-cell subsets to IL-7. Culture with high doses of IL-7 ( > 150 ng/ml) preferentially expanded CD8 T-cells, but lead to the dramatic loss of CD4 T-cells which favored growth in lower dosages of IL-7 ( > 10 ng/ml). This effect was due to the regulation of LCK, a kinase predominantly associated with the CD4 co-receptor. We found that transgenic expression of the CD4 co-receptor onto CD8 T-cells promoted their growth in lower concentrations of IL-7. Conversely, inhibition of LCK activity in CD4 T-cells restored their responsiveness to high doses of IL-7 as indicated by the activation of the transcription factor STAT5, in a manner similar to CD8 T-cells. Interestingly, not all CD8 T-cells expanded in high doses of IL-7 and this effect was specific to CD8 T-cells that expressed an activated memory phenotype. We found that IL-7 promoted the proliferation of CD8 T-cells through Cdc25A, a phosphatase required for cell cycle progression. Expression of a constitutively active Cdc25A could maintain T-cell survival and proliferation in the absence of IL-7, demonstrating that Cdc25A is a crucial transducer of IL-7 growth signals. Inhibition of Cdc25A was sufficient to decrease proliferation and down-regulate the expression of activation/ memory markers on CD8 T-cells in the presence of IL-7. Upon further study, we identified a novel role for IL-7 through Cdc25A in the regulation of CD62L, an adhesion molecule required for lymph node entry. Culture with high doses of IL-7 down-regulated the expression of CD62L, suggesting that high doses of IL-7 could affect the ability of T-cells to enter or re-enter the lymph nodes. Collectively, our findings demonstrate that IL-7 administration at the supraphysiological doses currently used in the clinical trials could have a negative impact on the growth of CD4 T-cells and the homing of CD8 T-cells to the lymph nodes, effects which can impede the generation of an effective immune response.