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A 9-year-old gelding presented with approximately 100 papillomas that covered about 75% of the distal penis. Biopsy was performed, and histology showed evidence of viral cytopathic change and koilocytosis. Polymerase chain reaction using DNA extracted from biopsied tissue amplified equine papillomavirus type 2 (EcPV-2) DNA sequences. Sixteen months later, the horse was re-examined and the appearance of the papillomas was unchanged. Equine papillomavirus type 2 DNA sequences were again amplified from both biopsied tissue and swabs of the penis. Papillomavirus was localized to the lesions by immunohistochemistry and in situ hybridization. An examination 2 years after the initial presentation revealed no detectable change in the appearance of the penis. The large number of papillomas and their failure to regress over an extended period support a clinical classification of papillomatosis. To the authors' knowledge, this is the first report of papillomatosis of the equine penis. This novel clinical manifestation suggests that persistent EcPV-2 infection is possible in horses. As there is evidence that EcPV-2 may promote development of equine penile squamous cell carcinoma, understanding the natural history of EcPV-2 infections may be important in preventing equine penile neoplasia.

Exercise during pregnancy may have long-lasting effects on offspring health. Musculoskeletal growth and development, metabolism, and later-life disease risk can all be impacted by the maternal environment during pregnancy. The skeleton influences glucose handling through the actions of the bone-derived hormone osteocalcin. The purpose of this study was to test the effects of moderate maternal exercise during pregnancy on the bone and body composition of the offspring in adult life, and to investigate the role of osteocalcin in these effects. Groups of pregnant Wistar rats either performed bipedal standing exercise to obtain food/water throughout gestation but not lactation, or were fed conventionally. Litters were reduced to 8/dam and pups were raised to maturity under control conditions. Whole body dual-energy x-ray absorptiometry, and ex vivo peripheral quantitative computed tomography scans of the right tibia were performed. At study termination blood and tissue samples were collected. Serum concentrations of fully and undercarboxylated osteocalcin were measured, and the relative expression levels of osteocalcin, insulin receptor, Forkhead box transcription factor O1, and osteotesticular protein tyrosine phosphatase mRNA were quantified. Body mass did not differ between the offspring of exercised and control dams, but the male offspring of exercised dams had a greater % fat and lower % lean than controls (p=0.001 and p=0.0008, respectively). At the mid-tibial diaphysis, offspring of exercised dams had a lower volumetric bone mineral density than controls (p=0.01) and in the male offspring of exercised dams the bone: muscle relationship was fundamentally altered. Serum concentrations of undercarboxylated osteocalcin were significantly greater in the male offspring of exercised dams than in controls (p=0.02); however, the relative expression of the measured genes did not differ between groups. These results suggest that moderate exercise during pregnancy can result in lasting changes to the musculoskeletal system and adiposity in offspring, in a sex-specific manner.

research has revealed a neuroendocrine connection between the skeleton and metabolism. Exercise alters both bone modeling and energy balance and may be useful in further developing our understanding of this complex interplay. However, research in this field requires an animal model of exercise that does not cause a physiological stress response in the exercised subjects. In this study, we develop a model of short-term voluntary exercise in the female rat that causes bone modeling without causing stress. Rats were randomly assigned to one of three age-matched groups: control, tower climbing, and squat exercise (rising to an erect bipedal stance). Exercise for 21 days resulted in bone modeling as assessed by peripheral quantitative computed tomography. Fecal corticosterone output was used to assess physiological stress at three time points during the study (preexercise, early exercise, and late in the exercise period). There were no differences in fecal corticosterone levels between groups or time points. This model of voluntary exercise in the rat will be useful for future studies of the influence of exercise on the relationship between skeletal and metabolic health and may be appropriate for investigation of the developmental origins of those effects. computed tomography; corticosterone; exercise; metabolism; stress RECENT ADVANCES IN OUR UNDERSTANDING of the dynamic relationship between body structure and metabolism have revealed a neuroendocrine connection between bone remodeling and energy balance, with both bone and fat acting as endocrine organs (14). The osteoblast-specific protein osteocalcin regulates glucose handling through effects on insulin secretion and sensitivity (33). This action is in turn mediated by the adipokine leptin, which inhibits insulin secretion through direct effects on pancreatic ␤-cells (18) and through inhibition of osteocalcin activity (25). The interplay between bone and metabolism has recently been further elucidated by the discovery that the Forkhead family transcription factor FoxO1, a key regulator of insulin handling in multiple tissues, also acts within the osteoblast to control osteocalcin expression and bioactivity (46).Exercise stimulates modeling of the musculoskeletal system (19, 55, 65), alters metabolism (40), and enhances brain function (17), and thus exercise provides an excellent means of exploring the neuroendocrine connection between bone, fat, and energy balance. The rat model of exercise has been used extensively to study the physiological effects of physical activity using such exercise modalities as swimming (24, 32), running (20,29,41,49,52), jumping (57), tower climbing (43), rising to an erect bipedal stance (11, 64), and weight lifting (62). The effects of exercise on bone have been widely characterized in the rat. Ovariectomized rats undergo changes in bone structure that are nearly identical to those seen in human osteoporosis (28,42), and these animals have proven useful for the study of exercise interventions in osteoporosis treatment (36).In examini...

effects of increased physical activity during pregnancy on the health of the offspring in later life are unknown. Research in this field requires an animal model of exercise during pregnancy that is sufficiently strenuous to cause an effect but does not elicit a stress response. Previously, we demonstrated that two models of voluntary exercise in the nonpregnant rat, tower climbing and rising to an erect bipedal stance (squat), cause bone modeling without elevating the stress hormone corticosterone. In this study, these same models were applied to pregnant rats. Gravid Wistar rats were randomly divided into three groups: control, tower climbing, and squat exercise. The rats exercised throughout pregnancy and were killed at day 19. Maternal stress was assessed by fecal corticosterone measurement. Maternal bone and soft tissue responses to exercise were assessed by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry. Maternal weight gain during the first 19 days of pregnancy was less in exercised than in nonexercised pregnant control rats. Fecal corticosterone levels did not differ between the three maternal groups. The fetuses responded to maternal exercise in a uterine positiondependent manner. Mid-uterine horn fetuses from the squat exercise group were heavier (P Ͻ 0.0001) and longer (P Ͻ 0.0001) and had a greater placental weight (P ϭ 0.001) than those from control rats. Fetuses from tower-climbing dams were longer (P Ͻ 0.0001) and had heavier placentas (P ϭ 0.01) than those from control rats, but fetal weight did not differ from controls. These models of voluntary exercise in the rat may be useful for future studies of the effects of exercise during pregnancy on the developmental origins of health and disease.pregnancy; bone; developmental origins of health and disease EVENTS THAT OCCUR DURING FETAL development can have longlasting effects on the health and later-life outcomes of the developing organism (25). Low birth weight in humans is associated with an increased risk of later-life diseases, such as coronary heart disease, hypertension, and insulin resistance (3). Exercise during pregnancy may significantly impact birth weight and later-life health, but the effects of maternal exercise during gestation on fetal growth are unclear, and studies in humans and animals have yielded varying results. Studies in humans have found that exercise during pregnancy was associated with birth weight that was reduced (4, 21, 27), unaffected (46), or increased (13, 26) in the offspring of exercising women. Comparison between studies is complicated by different exercise regimens, and many used self-reported exercise, rather than a standardized, supervised exercise program. Timing during pregnancy, intensity, and type of the exercise may influence its effects on the fetus. For example, moderate weight-bearing (treadmill, stair stepper, or step aerobics) exercise begun in early pregnancy has been shown to increase fetoplacental growth and birth weight (13), whereas a high volume of the same exerc...

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OBJECTIVE The aim of this study was to determine whether the pharmacokinetics of maropitant, administered SC as a commercially available maropitant-containing injectable product (Cerenia Injectable), differ when combined with lactated Ringer solution prior to administration. ANIMALS We used 6 adult spayed female Beagle dogs between 3 and 6 years of age, with a mean weight of 9.58 kg. PROCEDURES In this randomized crossover study, the dogs underwent 2 treatment protocols separated by a 14-day washout period: (1) an SC injection of 1 mg/kg of Cerenia Injectable (maropitant citrate; 10 mg/mL) and (2) 1 mg/kg of Cerenia Injectable diluted in 10 mL/kg of lactated Ringer injectable solution (LRS) given SC. Plasma maropitant concentrations were assessed by mass spectrometry. Pharmacokinetic analysis was performed using pharmacokinetic and pharmacodynamic data-analysis software to determine maximum plasma concentration (Cmax), time to reach maximum concentration, half-life, total exposure to the drug, mean residence time, clearance rate per fraction absorbed, and absorption and elimination kinetic parameters. RESULTS Cmax was reduced by 26% (P = .002), the absorption rate constant decreased 80% (P = .031), and the absorption half-life increased when Cerenia was administered diluted in LRS. CLINICAL RELEVANCE Administration of maropitant (Cerenia) diluted in LRS had a pharmacokinetic impact, resulting in a significantly reduced Cmax and slower absorption. Clinical efficacy was not assessed in this study.