Medicine and Health Sciences Commons^™

Mouse Oocyte Maturation And Embryo Development After Exposure To Vemurafenib (Plx4032), An Anti-Melanoma B-Raf V600e Inhibitor, Bo Liu

Theses and Dissertations in Biomedical Sciences

Vemurafenib is a selective B-Raf^V600E inhibitor in melanoma targeted therapy which also inhibits the wild type B- and C-Raf. In oocyte maturation, the C-Raf/MAPK pathway acts as an important self-enhancing and promoting system, w hereas in embryo development, the C-Raf/M APK pathway participates in pre- and post- implantation embryo proliferation and differentiation.

The hypothesis: Vemurafenib has detrimental effects on oocyte maturation and/or embryo development. Mouse oocytes and one cell (1C) mouse embryos were tested by ex vivo culturing with Vemurafenib in serial dilution. Oocytes were evaluated by cell cycle morphology, spindle formation and chromosomal alignment by im munofluorescence (IF) …

The Ultrastructure Of The Olfactory System In Two Species Of Short-Tailed Shrews, Blarina Brevicauda And Blarina Carolinensis, Lisa Johnson Byrum

Theses and Dissertations in Biomedical Sciences

Several studies of the fine structure of the olfactory system of rodents have been conducted, but very little research has been done on members of the Insectivora. The olfactory systems of the northern short-tailed shrew, Blarina brevicauda, and the southern short-tailed shrew, Blarina carolinensis, were examined by light and electron microscopy. These shrews were live trapped in the vicinity of Norfolk, Virginia throughout all months of the year. Olfactory tissues were processed following standard transmission and scanning electron microscopy protocols. The olfactory system structures investigated included the olfactory epitheliumlmucosa (OEM), main olfactory bulb (MOB), accessory olfactory bulb (AOB), …

Estrogen Regulation Of The Pregnant Baboon Placental 11Β-Hydroxysteroid Dehydrogenase (11Β-Hsd)-Catalyzed Metabolism Of Cortisol And Cortisone And Its Effect On The Development Of The Fetal Hypothalamic-Pituitary-Adrenal Axis, William Adair Davies

Theses and Dissertations in Biomedical Sciences

Pepe and Albrecht previously demonstrated that the estrogen-regulated change in transuteroplacental metabolism of cortisol (F) and cortisone (E) from preferential reduction (E to F) at midgestation to oxidation (F to E) near term results in a decline of bioactive cortisol crossing the placenta and reaching the fetus culminating in activation of the hypothalamic-pituitary adrenal axis of the baboon and the ontogenesis of rate-limiting steroidogenic enzymes culminating in de novo F secretion. Protein kinase A (PK-A) activity in the baboon fetal adrenal gland cytosolic fraction was increased 2-fold both at term [day 165 of gestation (term = 184 days)] and following …

Endothelial Nitric Oxide Synthase And Growth Factor Regulation Of Flow-Mediated Vascular Remodeling, David Anthony Tulis

Theses and Dissertations in Biomedical Sciences

This study was designed to characterize structural remodeling of male Wistar rat mesenteric arteries exposed to elevated blood flow in vivo for 1, 3, or 7 days. A series of arterial ligations induced blood flow increases in ileal and second-order branch arteries compared to same animal control vessels. Neither mean carotid nor local mesenteric arterial pressures changed significantly pre- to post-ligation. The primary flow-mediated force in both vessels was shear stress with possible involvement of acute stretch-induced wall stress in the ileal artery. Significant luminal expansion and medial wall hypertrophy occurred in the ileal and second-order arteries in a time-dependent …

Interaction Of Acth And Estradiol In The Regulation Of Growth, Differentiation, And Steroidogenic Maturation Of The Baboon Fetal Adrenal Gland, Maria Gomez Leavitt

Theses and Dissertations in Biomedical Sciences

The present study determined whether the growth of, as well as ACTH receptor and P-450 enzyme messenger ribonucleic acid and/or protein levels in the baboon fetal adrenal are dependent upon fetal pituitary ACTH during mid and late gestation and the mechanism by which placental estrogen modulates ACTH actions. Administration of betamethasone (3mg/day) to baboon mothers on days 60-99 of gestation and to the fetus (0.6 mg/, n = 4) or to the fetus (0.6mg) and mother (6 mg/ml; n = 4) every other day between days 150-164 of gestation (term = 184 days) decreased (P $53β-hydroxysteroid dehydrogenase-isomerase (3β-HSD(+)ctochrome P450 17α-hydroxylase, …

Differential Endometrial Responses Of Primates Vs Rodents: Screening For Antiproliferative Effects Of Antiprogestins, David Williams Burleigh

Theses and Dissertations in Biomedical Sciences

The antiprogestin, mifepristone, has previously been shown to noncompetitively inhibit estrogen-induced endometrial proliferation in nonhuman primates (van Uem et al., 1989; Wolf et al., 1989b; Neulen et al., 1990; Neulen et al., 1996). For both economical and ethical reasons, we are encouraged to identify comparative laboratory rodent models which can substitute the need to use primate models. In the following study, we compared capabilities of the rat uterine weight bioassay versus a primate uterine bioassay, to identify the noncompetitive antiestrogenic/antiproliferative effects of mifepristone.

Long-term ovariectomized monkeys were exposed to exogenous 17β-estradiol (E2) and mifepristone in doses and regimes already demonstrated …

Cellular Mechanisms Underlying Myogenic Reactivity In Isolated Arterioles, Hui Zou

Theses and Dissertations in Biomedical Sciences

The myogenic reactivity provides one of the principal mechanisms for blood flow autoregulation. The aims of the performed studies described in this dissertation were to test the role of [Ca²⁺]_i and MLC phosphorylation in arteriolar myogenic reactivity and further examine the source(s) of activator Ca²⁺ required to initiate and maintain myogenic vasoconstriction. In addition, the possible underlying mechanism of contractile protein expression was also addressed.

These studies used male Sprague Dawley rats of 200 ~ 350 grams body weight. Experiments were carried out using rat cremaster first order arterioles and mesenteric vessels. Gel electrophoresis and immunoblotting …