Thesis (Ph.D.)--Ohio University, August, 2009. / Title from PDF t.p. Release of full electronic text on OhioLINK has been delayed until September 1, 2012. Includes bibliographical references (p. 253-288)

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The metabolic heat generated by exercise must be dissipated to maintain body temperature within narrow physiological limits; during exercise and heat exposure, body water is lost via sweating to enable evaporative cooling of the body. When sweating takes place, total body water is reduced (without the intake of additional fluids) from each fluid compartment due to the free exchange of water between compartments with a concomitant loss of electrolytes, primarily sodium. A series of three investigations were undertaken to evaluate: 1) the efficacy of acute sodium citrate-chloride loading on endurance trained males and females as a viable means to expand extracellular fluid volume, 2) any menstrual cycle effects on renal handling of this sodium load at rest, and 3) if any subsequent hypervolaemia reduces the physiological strain of exercise in warm conditions in both genders. The first investigation examined eight endurance-trained (VO₂[max]: 58 ml�kg⁻��min⁻� (SD 5); 36 y (SD 11)) runners in a randomized double-blind crossover study. The participants ingested a high-sodium (HighNa⁺: 164 mmol Na⁺�L⁻�) or low-sodium (LowNa⁺: 10 mmol Na⁺�L⁻�) beverage (10 ml�kg⁻�) before running to exhaustion at 70% VO₂[max] in warm conditions (32�C, 50% RH, V[a]~1.5 m�s⁻�). Results indicate that HighNa⁺ increased PV before exercise (4.5% (SD 3.7)), calculated from Hct and [Hb]), whereas LowNa⁺ didn�t (0.0% (SD 0.5); P = 0.04), and involved greater time to exercise termination in those who were stopped due to ethical end point of 39.5�C and volitional exhaustion (39.5�C: 57.9 min (SD 6) vs. 46.4 min (SD 4); n = 5, P = 0.04; EXH: 96.1 min (SD 22) vs. 75.3 min (SD 21); n = 3, P = 0.03; HighNa⁺ vs. LowNa⁺ respectively). At equivalent times before exercise termination, HighNa⁺ also involved lower core temperature (38.9 vs. 39.3�C; P = 0.00) and perceived exertion (P = 0.01), and a tendency for lower heart rate (164 vs. 174 bpm; P = 0.08). The main purpose of the second investigation was to investigate the efficacy of an acute sodium load on endurance trained women�s plasma volume and renal mechanisms across the menstrual cycle at rest. This was evaluated by inducing a sodium-mediated plasma volume expansion using HighNa⁺ at rest during the last high hormone week of the OCP cycle (HH[ocp]) or the late-luteal phase of the natural cycle (LUT[nat]) and during the low hormone sugar pill week of the OCP cycle (SUG[ocp]) or during the early follicular phase of the natural cycle (FOL[nat]. Thirteen women completed the study with one woman on a progestin-only pill (results were used for case study, not statistical analyses) and were assigned to one of two groups: 1) control (NAT, n = 6, 24 y (SD 5), 53 ml�kg�ml⁻� (SD 3)) or oral contraceptive pill (OCP, n = 6, progestin only n = 1, 29 y (SD 6), 51 ml�kg�ml⁻� (SD 2)) group according to their usage status. Across the four-hour post loading time there was greater plasma volume expansion in SUG[ocp] and FOL[nat] vs. LUT[nat] and HH[ocp] (5.06% (SD1.16) vs. 3.35% (SD 0.23), P = 0.02). OCP usage did not reliably alter the hypervolaemic response (P = 0.27), and this was not dependent on phase of cycle (P = 0.32). Plasma volume expansion occurred across both types and phases of the menstrual cycle with evidence that estradiol interactions with AVP, P[osm] and body water retention are stronger in the low hormone phase of the OCP than in the follicular phase of the natural cycle; illustrated by greater overall water retention after an acute sodium+water load. The third investigation was conducted during the high hormone phase of both OCP and NAT menstrual cycles to further examine sodium-loading effects on the physiological capacity of exhaustive cycling in warm conditions. Thirteen endurance-trained (VO₂[peak] 52 ml�kg⁻��min⁻� (SD 2); 26 y (SD 6), 60.8 kg (SD 5), mean (SD)) cyclists completed this double-blind, crossover experiment during the high hormone phase of the menstrual cycle. Cyclists ingested a concentrated sodium (HighNa⁺: 164 mmol Na⁺�L⁻�) or low-sodium (LowNa⁺: 10 mmol Na⁺�L⁻�) beverage (10 ml�kg⁻�) before cycling to exhaustion at 70% VO₂[max] in warm conditions (32�C, 50% RH, V[a]~5.6 m�s⁻�). HighNa⁺ increased PV before exercise, similar to that of the men in the first investigation, whereas LowNa⁺ didn�t (4.4% (SD 1.2) vs. -1.9% (SD 1.3); P < 0.0001), and involved greater time to exhaustion (98.6 min (SD 25.6) vs. 78.5 min (SD 24.6); P < 0.0001). There was a higher baseline core temperature and faster rate of change for HH[ocp] for both beverage conditions (HighNa⁺: 37.15 (SD 0.6) vs. 36.92�C (SD 0.4); P = 0.05, LowNa⁺: 37.04 (SD 0.6) vs. 36.90�C (SD 0.4), P = 0.05; HH[ocp] vs. LUT[nat], respectively). Through this series of investigations a greater understanding was achieved of fluid balance and the effect of pre-exercise hypervolaemia between genders; pre-exercise ingestion of a concentrated sodium beverage increased plasma volume before exercise and involved less thermoregulatory and the actual and perceived physiological strain during exercise and increased endurance in warm conditions.

Thesis (Ph.D.)--Duquesne University, 2008. / Title from document title page. Abstract included in electronic submission form. Includes bibliographical references (p. 231-271) and index.

Thesis (Ph. D.)--University of Missouri-Columbia, 1999. / Typescript. Vita. Includes bibliographical references (leaves 105-113). Also available on the Internet.

Thesis (M.S.)--University of Wisconsin--Madison, 1964. / eContent provider-neutral record in process. Description based on print version record. Bibliography: 3 l. at end.

Philosophiae Doctor - PhD / Heterosexual transmission of HIV-1 via the female genital tract is the leading route of HIV infection in sub-Saharan Africa. Viruses then traffic between the cervical compartment and blood ensuring pervasive infection. Previous studies have however reported the existence of genetically diverse viral populations in various tissue types, each evolving under separate selective pressures within a single individual, though it is still unclear how compartmentalization dynamics change over acute and chronic infection in the absence of ARVs. To better characterize intrahost evolution and the movement of viruses between different anatomical tissue types, statistical and phylogenetic methods were used to reconstruct temporal dynamics between blood plasma and cervico-vaginal lavage (CVL) derived HIV-1 subtype C gp120 envelope sequences. A total of 206 cervical and 253 blood plasma sequences obtained from four treatment naïve women enrolled in the CAPRISA Acute Infection study cohort in South Africa were evaluated for evidence of genotypic and phenotypic differences between viral populations from each tissue type up to 3.6 years post-infection. Evidence for tissue-specific differences in genetic diversity, V-loop length variation, codon-based selection, co-receptor usage, hypermutation, recombination and potential N-linked glycosylation (PNLG) site accumulation were investigated. Of the four participants studied, two anonymously identified as CAP270 and CAP217 showed evidence of infection with a single HIV-1 variant, whereas CAP177 and CAP261 showed evidence of infection by more than one variant. As a result, genetic diversity, PNLGs accumulation and the number of detectable recombination events along the gp120 env region were lowest in the former patients and highest in the latter. Overall, genetic diversity increased over the course of infection in all participants and correlated significantly with viral load measurements from the blood plasma in one of the four participants tested (i.e. CAP177). Employing a structured coalescent model approach, rates of viral migration between anatomical tissue types on time-measured genealogies were also estimated. No persistent evidence for the existence of separate viral populations in the cervix and blood plasma was found in any of the participants and instead, sequences generally clustered together by time point on Bayesian Maximum Clade Credibility (MCC) trees. Clades that were monophyletic by tissue type comprised mostly of low diversity or monotypic sequences from the same time point, consistent with bursts of viral replication. Tissue-specific monophyletic clades also generally contained few sequences and were interspersed among sequences from both tissue-types. Tree and distance-based statistical tests were employed to further evaluate the degree to which cervical and blood plasma viruses clustered together on Bayesian MCC trees using the Slatkin-Maddison (S-M), Simmonds Association index (AI), Monophyletic Clade (MC), Wright’s measure of population subdivision (FST) and Hudson’s Nearest Neighbour (Snn) statistics, in the presence and absence of monotypic and low diversity sequences. Statistical evidence for the presence of tissue-specific population structure disappeared or was greatly reduced after the removal of monotypic and low diversity sequences, except in CAP177 and CAP217, in 3/5 of longitudinal tree and distance-based tests. Analysis of phenotypic differences between viral populations from the blood plasma and cervix revealed inconsistent tissue-specific patterns in genetic diversity, codon-based selection, co-receptor usage, hypermutation, recombination, V-loop length variation and PNLG site accumulation during acute and chronic infection among all participants. There is therefore no evidence to support the existence of distinct viral populations within the blood plasma and cervical compartments longitudinally, however slightly constrained populations may exist within the female genital tract at isolated time points, based on the statistical findings presented in this study.

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