Studies on the teratogenicity of anabasine in a rat model.

A number of plant toxins have been shown to be teratogenic to livestock. The teratogenic action of some of these alkaloids is mediated by nicotinic acetylcholine receptors (nAChR). However, for many of these alkaloids it is difficult to obtain sufficient quantities of individual alkaloids to perform teratology studies in livestock species. Therefore the objective of this study was to determine if a rat model can be utilized to characterize the teratogenic nature of individual plant toxins that are nAChR agonists. In this study, we evaluated the teratogenicity of anabasine by feeding pregnant rats anabasine-containing rodent chow from gestational day (GD) 6-21. On GD21, the dams were euthanized and the gravid uteri were removed. The gravid uteri and individual pups were weighed. The pups were evaluated for bone malformations including cleft palate and scoliosis. Overall, the results of this study suggest that the rat is not a good model to study the teratogenicity of plant toxins that are nAChR agonists. It is possible that in the rat model, anabasine administered orally via the chow may not result in sufficient reduction in fetal movement to cause the significant malformations observed in livestock species.

Neem-tree (Azadirachta indica Juss.) extract as a feed additive against the American dog tick (Dermacentor variabilis) in sheep (Ovis aries).

Acaricides can be conveyed to ticks via the blood of their hosts. As fruit and kernel extracts from the Meliaceae family, and, in particular the tetranortriterpenoid azadirachtin (AZA) inhibits tick egg production and embryogenesis in the Ixodidae ticks, we investigated the effects of Neem Azal, an extract containing 43% AZA, given as a feed additive to lambs artificially infested with engorging adult Dermacentor vairiabilis ticks. After tick attachment, the lambs were allotted to three dietary treatments: AZA0 (control, n=10), AZA0.3 (n=5), and AZA0.6 (n=5), with feed containing 0%, 0.3%, and 0.6% AZA on DM basis, respectively. In half of the AZA0 lambs, ticks were sprayed on day 4 after attachment with an ethanol:water:soap emulsion containing 0.6% AZA (AZA0S). In spite of its very pungent odor, the neem extract was well accepted by all but one lamb. No differences were found between treatment groups in liver enzymes in blood, and there was no indication of toxicity. The plasma AZA concentrations after 7 and 14 days of feeding AZA were (4.81 and 4.35 microg/mL) for the AZA0.6 and (3.32 and 1.88 microg/mL) for the AZA0.3 treatments, respectively (P<0.0001). Treatments were not lethal to ticks, but tick weights at detachment were 0.64, 0.56, 0.48, and 0.37 g for ticks from the AZA0, AZA0.3, AZA0S, and AZA0.6 treatments (P<0.04), respectively, suggesting that blood AZA impaired blood-feeding. The highest mortality rate after detachment was for AZA0.6 (P<0.09). As AZA affects embryo development and ticks at the molting stages, we expect that following treatments of hosts for longer periods, one-host ticks will be more affected than the three-host tick D. variabilis.

Acute phase responses of pigs challenged orally with Salmonella typhimurium.

This study evaluated responses of the systemic endocrine stress (cortisol) and growth (IGF-I, GH) axes, as well as those of inflammatory mediators (prostaglandin E2 [PGE2] and tumor necrosis factor alpha [TNFalpha]), to active infection with Salmonella typhimurium. Eighteen crossbred barrows were penned individually with ad libitum access to feed and water. After an acclimation period, jugular catheters were placed in all animals. Control pigs received sterile broth orally (CON, n = 7), whereas the treated pigs (S.TYP, n = 11) received 3 x 10(9) cfu of S. typhimurium orally. Plasma was collected at 6-h intervals from -48 to 120 h. Body weights, feed intake, and rectal temperatures also were monitored. Rectal temperatures were elevated in S.TYP pigs (P < .01) relative to CON pigs by 12 h, peaked at 42 h (P < .001), and remained elevated throughout the remainder of the study. Feed intake was reduced maximally in S.TYP pigs at 48 h (P < .001) and remained reduced through 120 h after the challenge. Daily body weight gain also was reduced during the 2 wk following infection (P < .001). Plasma cortisol concentrations increased (P < .05) at 18 h after the challenge in S.TYP pigs and remained elevated generally until 60 h after infection. A marked suppression of plasma IGF-I occurred in S.TYP pigs beginning at 30 h after infection (P < .001), and it remained lower through 108 h. Plasma GH was not affected consistently by treatment, nor did infection alter plasma TNFalpha and PGE2. Taken together, the results reveal that infectious processes produce profound alterations in the endocrine stress and the somatotropic axis, and this may occur in the absence of significant changes in systemic proinflammatory mediators.

Integrated adrenal, somatotropic, and immune responses of growing pigs to treatment with lipopolysaccharide.

The objective of this research was to provide an integrated look at systemic adrenal, somatotropic, and immune responses of growing pigs to challenge with lipopolysaccharide (LPS). Weaned pigs were challenged intraperitoneally with 100 microg/kg BW of LPS or sterile saline, and rectal temperature and blood data were collected for 72 h. Daily feed intake also was monitored. Plasma was analyzed for concentrations of cortisol, tumor necrosis factor alpha (TNFalpha), the acute phase protein haptoglobin, growth hormone (GH), insulin-like growth factor I (IGF-I), and prostaglandin E2 (PGE2). As expected, LPS decreased feed intake, stimulated a febrile response, and activated the hypothalamic-pituitary-adrenal (HPA) axis as demonstrated by increased cortisol levels. Cortisol reached maximum elevation 2 h after treatment (P < .001) and remained elevated through 12 h (P < .001). Circulating TNFalpha was increased by LPS at 2 and 4 h after treatment (P < .001), and an apparent (not statistically significant) increase in haptoglobin also occurred in challenged animals. The LPS injection suppressed IGF-I by 2 h following treatment (P < .01), and circulating IGF-I remained reduced relative to controls through 44 h. Overall, GH was increased in LPS-treated pigs (P < .05), although the treatment x time interaction was not significant. Plasma PGE2 was increased transiently at 2 h (P < .05) and then subsequently suppressed at 4, 8, and 12 h following LPS (P < .05). This study provides a comprehensive view of systemic effects of LPS on components of the HPA, growth, and immune axes. In addition, these are the first data to document changes in circulating PGE2 in unrestrained animals during the early hours of the acute phase response to LPS.

Pituitary function in the acute phase response in domestic farm animals: cytokines, prostaglandins, and secretion of ACTH.

Contained in this report is a review of available data on pituitary cytokines in domestic species of agricultural importance. The concept is advanced that the pituitary gland is essential to appropriate generation of host defense mechanisms and thus should be considered among other tissues contributing to innate immunity. The functions of these intrapituitary cytokines, principally IL-6, are discussed in the context of potential regulation of the pituitary-adrenal axis (ACTH secretion) via intrapituitary PGE2 generation during the acute-phase response to infectious/inflammatory stimuli. Data from other species are cited as appropriate for comparative purposes and elaboration of proposed mechanisms. However, the scope of the review is not intended to comprehensively cover the vast literature on proinflammatory cytokines and prostaglandins generated peripherally and centrally during host responses to inflammatory stimuli.

Estrus, ovulation, luteinizing hormone, and suckling-induced hormones in mastectomized cows with and without unrestricted presence of the calf.

Angus x Hereford multiparous cows were assigned to four treatments: 1) mastectomized+calf weaned at birth (MCW; n = 7); 2) mastectomized+calf presence restricted to noninguinal contact (MCR; n = 7); 3) mastectomized+unrestricted calf presence (MCP; n = 7); and 4) udder-intact cows+unrestricted calf presence (UICP; n = 8). Except for MCW cows, cow-calf pairs were penned together individually from parturition (d 0) until d 35 when calves were weaned. On d 7, calves in MCP and UICP treatments were separated overnight from their dams, and before and upon reunion, blood samples were collected from the cows to assess changes in oxytocin, cortisol, and prolactin. Calves in the MCP and UICP treatments attempted to or suckled their dams for a similar duration upon reunion, respectively. Concentrations of cortisol and percentage of change in oxytoxin and prolactin were increased (P < .05) for up to 12 min in MCP cows after reunion with their calves. Average concentrations of serum LH in samples collected on d 14, 21, 28, and 35 did not differ in noncyclic cows among treatments within day postpartum (except for greater [P < .05] LH in MCW cows on d 21). However, MCP cows had more (P < .05) LH pulses (d 21), greater (P < .05) variability in LH pulses (d 21), greater (P < .05) variability in LH concentrations, and greater (P < .05) average maximum concentrations of LH than UICP cows after d 14. Intervals to first ovulation were similar in MCW and MCR cows but shorter (P < .01) than those in MCP and UICP cows. Attempted suckling of mastectomized dams by their calves was associated with increased serum cortisol and percentage of increase in serum oxytocin and prolactin. Despite increased LH in MCP cows, intervals to first ovulation did not differ from those of UICP cows.