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Wells, P. G., Bhuller, Y., Chen, C. S., Jeng, W., Kasapinovic, S., Kennedy, J. C., et al. (2005). Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species. Toxicol Appl Pharmacol, 207(2 Suppl), 354–366.
Abstract: Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reactive oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction. This minireview focuses upon several model drugs (phenytoin, thalidomide, methamphetamine), environmental chemicals (benzo[a]pyrene) and gamma irradiation to examine this hypothesis in vivo and in embryo culture using mouse, rat and rabbit models. Embryonic prostaglandin H synthases (PHSs) and lipoxygenases bioactivate xenobiotics to free radical intermediates that initiate ROS formation, resulting in oxidation of proteins, lipids and DNA. Oxidative DNA damage and embryopathies are reduced in PHS knockout mice, and in mice treated with PHS inhibitors, antioxidative enzymes, antioxidants and free radical trapping agents. Thalidomide causes embryonic DNA oxidation in susceptible (rabbit) but not resistant (mouse) species. Embryopathies are increased in mutant mice deficient in the antioxidative enzyme glucose-6-phosphate dehydrogenase (G6PD), or by glutathione (GSH) depletion, or inhibition of GSH peroxidase or GSH reductase. Inducible nitric oxide synthase knockout mice are partially protected. Inhibition of Ras or NF-kB pathways reduces embryopathies, implicating ROS-mediated signal transduction. Atm and p53 knockout mice deficient in DNA damage response/repair are more susceptible to xenobiotic or radiation embryopathies, suggesting a teratological role for DNA damage, consistent with enhanced susceptibility to methamphetamine in ogg1 knockout mice with deficient repair of oxidative DNA damage. Even endogenous embryonic oxidative stress carries a risk, since untreated G6PD- or ATM-deficient mice have increased embryopathies. Thus, embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk.
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Crosby, M. B., Zhang, J., Nowling, T. M., Svenson, J. L., Nicol, C. J., Gonzalez, F. J., et al. (2006). Inflammatory modulation of PPAR gamma expression and activity. Clin Immunol, 118(2-3), 276–283.
Abstract: Nitric oxide (NO) production increases with age in the lupus-prone MRL/lpr mouse, paralleling disease activity. One mechanism for excess NO production in MRL/lpr mice may be a defect in down-regulatory mechanisms of the iNOS pathway. A potential modulator of NO is the nuclear hormone receptor peroxisome proliferation activated receptor gamma (PPARgamma). We demonstrate that renal PPARgamma protein expression was altered as disease progressed in MRL/lpr mice, which paralleled increased iNOS protein expression. Additionally, MRL/lpr-derived primary mesangial cells expressed less PPARgamma than BALB/c mesangial cells and produced more NO in response to LPS and IFNgamma. Furthermore, PPARgamma activity was reduced in mesangial cells following exposure to inflammatory mediators. This activity was restored with the addition of a NOS enzyme inhibitor. These results indicate that the activation of inflammatory pathways may lead to reduced activity and expression of PPARgamma, further exacerbating the disease state.
Keywords: Age Factors; Animals; Cell Line, Transformed; Cells, Cultured; Female; Inflammation Mediators/*physiology; Kidney/metabolism; Mesangial Cells/metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred MRL lpr; Mice, Knockout; Nitric Oxide/biosynthesis; Nitric Oxide Synthase Type II/biosynthesis/genetics; PPAR gamma/*biosynthesis/*genetics/metabolism; Up-Regulation/immunology
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Haslam, S. M., Brown, S. N., Wilkins, L. J., Kestin, S. C., Warriss, P. D., & Nicol, C. J. (2006). Preliminary study to examine the utility of using foot burn or hock burn to assess aspects of housing conditions for broiler chicken. Br Poult Sci, 47(1), 13–18.
Abstract: 1. Eleven broiler chicken farms, representing 4 production system types, were visited during the last 5 d of the flock cycle: bird and flock details were recorded. Litter friability was assessed at 9 sites within the house, atmospheric ammonia was measured at three sites and bird cleanliness was assessed on a numerical rating scale. 2. For these flocks, hock burn, foot burn and breast burn were measured at the processing plant by standardised assessors. 3. Significant correlations were identified between the percentage of birds with foot burn and average litter score, average house ammonia concentrations and feather score. 4. No correlation was found between the percentage of birds with hock burn or breast burn and average litter scores, average ammonia concentrations or feather score. 5. No correlation was found between stocking density and foot burn, hock burn or breast burn.6. If confirmed, these findings may have implications for the draft EU Broiler Directive, for which it is proposed that permitted stocking density on farm may be determined by the incidence and severity of contact dermatitis measured on plant.
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Nicol, C. J., Brown, S. N., Glen, E., Pope, S. J., Short, F. J., Warriss, P. D., et al. (2006). Effects of stocking density, flock size and management on the welfare of laying hens in single-tier aviaries. Br Poult Sci, 47(2), 135–146.
Abstract: Management practices, stocking rate and flock size may affect laying hen welfare but there have been few replicated studies in commercial non-cage systems that investigate this. This study used a broad range of physical and physiological indicators to assess the welfare of hens in 36 commercial flocks. Six laying period treatments were examined with each treatment replicated 6 times. It was not possible to randomly allocate treatments to houses, so treatment and house were largely confounded. Three stocking rates were compared: 7 birds/m(2) (n = 2450), 9 birds/m(2) (n = 3150) and 12 birds/m(2) in either small (n = 2450) or large (n = 4200) flocks. In addition, at 12 birds/m(2), in both small and large flocks, birds were subjected to either standard (SM) or modified (MM) management. MM flocks had nipple drinkers and no nest-box lights. Bone strength, fracture incidence, heterophil:lymphocyte (H:L) ratio, live weight, organ weights, serum creatine, serum osmolality, muscle pH and faecal corticosterone were measured on samples of birds at the end of the rearing period and at the end of lay. During the laying period, mortality, production and integument condition were recorded at regular intervals. Birds housed at 9 birds/m(2) had higher mortality than birds housed at 12 birds/m(2) by the end of lay, but not higher than birds housed at 7 birds/m(2). Birds housed at 7 and 9 birds/m(2) had lower percent liver weight, and worse plumage condition than most of the 12 bird/m(2) treatments. Modified management tended to improve plumage condition. There were no clear effects of flock size on the welfare indicators recorded. At the end of the rearing period fracture incidence was almost negligible and H:L ratio was within a normal range. By the end of lay fracture incidence was 60% and H:L ratio was high, with no treatment effect for either measure. This, together with information on faecal corticosterone, feather loss and mortality, suggests that the welfare of birds in all treatments was relatively poor by the end of lay.
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Dixon, G., Green, L. E., & Nicol, C. J. (2006). Effect of diet change on the behavior of chicks of an egg-laying strain. J Appl Anim Welf Sci, 9(1), 41–58.
Abstract: Injurious pecking has serious welfare consequences in flocks of hens kept for egg laying, especially when loose-housed. Frequent diet change is a significant risk for injurious pecking; how the mechanics of diet change influence pecking behavior is unknown. This study investigated the effect of diet change on the behavior of chicks from a laying strain. The study included a 3-week familiarity phase: 18 chick pairs received unflavored feed (Experiment 1); 18 pairs received orange oil-flavored (Experiment 2). All chicks participated in a dietary preference test (P); a diet change (DC); or a control group (C), 6 scenarios. All P chicks preferred unflavored feed. In Experiment 1, DC involved change from unflavored to orange-flavored; Experiment 2, orange- flavored to unflavored. Compared with controls, Experiment 2 DC chicks exhibited few behavioral differences; Experiment 1 DC chicks exhibited increased behavioral event rates on Days 1 and 7. They pecked significantly longer at their environment; by Day 7, they showed significantly more beak activity. There was little evidence of dietary neophobia. Change from more preferred to less preferred feed led to increased activity and redirected pecking behavior.
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McGreevy, P. D., Cripps, P. J., French, N. P., Green, L. E., & Nicol, C. J. (1995). Management factors associated with stereotypic and redirected behaviour in the thoroughbred horse. Equine Vet J, 27(2), 86–91.
Abstract: A greater knowledge of the effect of management factors is required to investigate the ontogeny of abnormal behaviour in the stabled horse. A postal survey of racehorse (flat) trainers yielded information about 22 yard and management factors. The relationship of the factors to the prevalence of abnormal behaviour was analysed by logistic regression. Management factors related to the time spent in the stable showed the strongest associations with stereotypic behaviour. The risk of horses performing abnormal behaviour increased: 1) as the amount of forage fell below 6.8 kg/day, 2) when bedding types other than straw were used, 3) when the total number of horses on the yard was fewer than 75, 4) in association with box designs that minimised contact between neighbouring horses, 5) when hay, rather than other types of forage, was used.
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McGreevy, P. D., Richardson, J. D., Nicol, C. J., & Lane, J. G. (1995). Radiographic and endoscopic study of horses performing an oral based stereotypy. Equine Vet J, 27(2), 92–95.
Abstract: There is confusion in the veterinary literature concerning the definition of oral based stereotypies in the horse. This study reports the use of fluoroscopy and endoscopy during cribbiting/wind-sucking in afflicted horses. This permitted observations of movements of the pharyngeal and oesophageal tissues and of the air column within during the stereotypic behaviour. The findings reported show that the sequence of events during crib-biting/wind-sucking is not related to deglutition and that air is not swallowed to the stomach. Transient dilation of the upper oesophagus was recorded and the characteristic noise of wind-sucking coincided with the in-rush of air through the cricopharynx. The oesophageal distension was relieved when the air returned to the pharynx although small quantities passed caudally. It is proposed that the role of contraction of the strap muscles of the neck is to create a pressure gradient in the soft tissues surrounding the oesophagus which provokes movement of air from the pharynx into the oesophagus. The findings suggest that the definitions currently used in the sale of horses are in need of revision.
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McGreevy, P. D., French, N. P., & Nicol, C. J. (1995). The prevalence of abnormal behaviours in dressage, eventing and endurance horses in relation to stabling. Vet. Rec., 137(2), 36–37.
Abstract: The behaviour of horses competing in different disciplines was studied and the relationship between the time they spent out of the stable and the prevalence of abnormal behaviour was examined. The owners of dressage, eventing and endurance horses were sent a questionnaire and a total of 1101 responses were received, giving data on 1750 horses. The behaviours studied were wood-chewing, weaving, crib-biting/wind-sucking and box-walking. The reported percentage prevalences of abnormal behaviour for the dressage, eventing and endurance horses were 32.5, 30.8 and 19.5, respectively. The relationship between the time spent in the stable and the prevalence of abnormal behaviour was examined by chi 2 tests which showed that there were significant linear trends for the eventing group (P < 0.001) and the dressage group (P < 0.05). It is concluded that the time a horse spends out of the stable is related to the discipline for which it is being trained and in dressage and eventing horses the time spent in a stable is correlated with an increased risk of abnormal behaviour.
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