Edelman A.B.,Oregon Health And Science University |
Jensen J.T.,Oregon National Primate Center |
Doom C.,Oregon National Primate Center |
Hennebold J.D.,Oregon National Primate Center
Contraception | Year: 2013
Background: Ovarian prostaglandins are critical in normal ovulation processes; thus, their inhibition may provide contraceptive benefits. This study was performed to determine the effect of the cyclooxygenase-2 (COX2) inhibitor celecoxib on ovulation and luteal events in women. Study Design: The study had a randomized, double-blind, crossover design. Ovulatory, reproductive-aged women underwent ovarian ultrasound and serum hormone monitoring during four menstrual cycles (control cycle, treatment cycle 1, washout cycle, treatment cycle 2). Subjects received study drug (oral celecoxib 400 mg or placebo) either (a) once daily starting on cycle day 8 and continuing until follicle rupture or the onset of next menses if follicle rupture did not occur [pre-luteinizing hormone (LH) surge dosing] or (b) once daily beginning with the LH surge and continuing for 6 days (post-LH surge dosing). Subjects were randomly assigned to one of the above treatment schemes and received the other in the subsequent treatment cycle. The main outcomes were evidence of ovulatory and luteal dysfunction as determined by inhibited/delayed follicle rupture and reduced luteal progesterone synthesis or lifespan, respectively. Results: A total of 20 women enrolled and completed the study (Group 1=10, Group 2=10), with similar demographics between groups. Nineteen subjects exhibited normal ovulation in the control cycle (one had a blunted LH peak). In comparison to control cycles, treatment cycles resulted in a significant increase in ovulatory dysfunction [pre-LH treatment: 30% (6/20), p=.04; post-LH treatment: 25% (5/20), p=.04]. Mean peak progesterone, estradiol, and LH levels and luteal phase length did not differ significantly between control and either treatment cycle. Conclusions: Although treatment with celecoxib before or after the LH surge increases the rate of ovulatory dysfunction, most women ovulate normally. Thus, this selective COX2 inhibitor appears to be of limited usefulness as a potential emergency contraceptive. © 2013 Elsevier Inc. All rights reserved.
Sullivan E.L.,Oregon National Primate Center |
Sullivan E.L.,Oregon Health And Science University |
Cameron J.L.,Oregon National Primate Center |
Cameron J.L.,Oregon Health And Science University |
Cameron J.L.,University of Pittsburgh
American Journal of Physiology - Regulatory Integrative and Comparative Physiology | Year: 2010
To study changes in energy balance occurring during the initial phases of dieting, 18 adult ovariectomized female monkeys were placed on a low-fat diet, and available calories were reduced by 30% compared with baseline consumption for 1 mo. Surprisingly, there was not significant weight loss; however, daily activity level (measured by accelerometry) decreased soon after diet initiation and reached statistical significance by the 4th wk of dieting (18 ± 5.6% decrease, P = 0.02). During a 2nd mo of dieting, available calories were reduced by 60% compared with baseline consumption, leading to 6.4 ± 1.7% weight loss and further suppression of activity. Metabolic rate decreased by 68 ± 12 kcal/day, with decreased activity accounting for 41 ± 9 kcal/day, and the metabolic activity of the weight lost accounting for 21 ± 5 kcal/day. A second group of three monkeys was trained to run on a treadmill for 1 h/day, 5 days/wk, at 80% maximal capacity, leading to increased calorie expenditure of 69.6 ± 10.7 kcal/day (equivalent to 49 kcal/day for 7 days). We conclude that a diet-induced decrease in physical activity is the primary mechanism the body uses to defend against diet-induced weight loss, and undertaking a level of exercise that is recommended to counteract weight gain and promote weight loss is able to prevent the compensatory decrease in physical activity-associated energy expenditure that slows diet-induced weight loss. Copyright © 2010 the American Physiological Society.
Frias A.E.,Oregon Health And Science University |
Frias A.E.,Oregon National Primate Center |
Grove K.L.,Oregon National Primate Center
Seminars in Reproductive Medicine | Year: 2012
The increased obstetric risks of maternal obesity have been well described. These include increased risks of gestational diabetes mellitus, preeclampsia, stillbirth, and cesarean delivery. The fetal/neonatal consequences of prenatal maternal obesity have received less attention. In addition to an increased risk of stillbirth, the fetal/neonatal consequences include increased adiposity and a metabolic status that increases the lifetime risk of obesity and diabetes. This review focuses on the clinical obstetric consequences of maternal obesity and highlights recent mechanistic insights on fetal programming as well as evidence suggesting that prenatal care provides a unique opportunity to ameliorate these risks and decrease the cycle of childhood obesity. Copyright © 2012 by Thieme Medical Publishers, Inc.
Tomita T.,Oregon Health And Science University |
Tomita T.,Oregon National Primate Center
Digestive Diseases and Sciences | Year: 2012
Background: PGP 9.5 is a cytoplasmic protein and is a specific marker for neurites and neurons. Aims: Using anti-PGP 9.5, this study aimed to localize nerve fibers in normal colons, polyps, adenomas and adenocarcinomas. Methods: Colonic polyps, adenomas and T 1 to T 3 adenocarcinomas with adjacent normal colon were immunostained for PGP 9.5 using rabbit anti-PGP 9.5. Results: In normal colon, numerous nerve fibers were localized in inner and outer muscles, from which submucosa and lamina propria were innervated. In hyperplastic polyps and tubular adenomas, the stalk revealed Meissner's plexus and large-diameter nerve fibers, and fine nerve fibers innervated abundantly in lamina propria of hyperplastic polyps and small tubular adenomas. In villous adenomas, large-diameter nerve fibers and Meissner's plexus were localized in the stalk whereas a few or no fine nerve fibers were localized in fine stroma. In adenocarcinomas, more fine fibers were localized in submucosal stroma adjacent to the invading carcinoma in T 1 carcinomas but there were no nerve fibers in the midst of tumors in T 2 and T 3 carcinomas. There were focally and sporadically increased nerve fibers adjacent to invading cancer nests in 5 of 8 T 2 cases. In T 3 carcinomas, fragmented Auerbach's plexus were noted in cancer-invaded colonic muscles and there were no increased fine nerve fibers in the cancer-invaded subserosa in the majority of cases. PGP 9.5 immunostaining revealed tumor-associated neurogenesis in submucosa but no obviously increased nerve fibers within cancer-invaded muscles. Conclusions: This lack of tumor-associated neurogenesis supports insidious and often silent clinical presentation of colonic carcinomas until invading through the colonic wall to adjacent organs. © 2011 Springer Science+Business Media, LLC.
Wang X.,Oregon Health And Science University |
Kroenke C.D.,Oregon National Primate Center |
Kroenke C.D.,Oregon Health And Science University
Alcohol Research: Current Reviews | Year: 2015
It is well recognized that fetal alcohol exposure can profoundly damage the developing brain. The term fetal alcohol spectrum disorder (FASD) describes the range of deficits that result from prenatal alcohol exposure. Over the past two decades, researchers have used magnetic resonance imaging (MRI) as a noninvasive technique to characterize anatomical, physiological, and metabolic changes in the human brain that are part of FASD. As using animal models can circumvent many of the complications inherent to human studies, researchers have established and explored a number of models involving a range of species. Using MRI-based modalities, the FASD animal models have demonstrated decreased brain volume and abnormal brain shape, disrupted cellular morphology differentiation, altered neurochemistry, and blood perfusion. These animal studies have facilitated characterization of the direct effects of ethanol; in many cases identifying specific sequelae related to the timing and dose of exposure. Further, as a result of the ability to perform traditional (such as histological) analyses on animal brains following neuroimaging experiments, this work leads to improvements in the accuracy of our interpretations of neuroimaging findings in human studies. © 2015, National Institute on Alcohol Abuse and Alcoholism (NIAAA). All rights reserved.