Pharmacokinetics and dynamics of mycophenolate mofetil after single‐dose oral administration in juvenile dachshunds

Mycophenolate mofetil (MMF) is recommended as an alternative/complementary immunosuppressant. Pharmacokinetic and dynamic effects of MMF are unknown in young‐aged dogs. We investigated the pharmacokinetics and pharmacodynamics of single oral dose MMF metabolite, mycophenolic acid (MPA), in healthy juvenile dogs purpose‐bred for the tripeptidyl peptidase 1 gene (TPP1) mutation. The dogs were heterozygous for the mutation (nonaffected carriers). Six dogs received 13 mg/kg oral MMF and two placebo. Pharmacokinetic parameters derived from plasma MPA were evaluated. Whole‐blood mitogen‐stimulated T‐cell proliferation was determined using a flow cytometric assay. Plasma MPA C_max (mean ± SD, 9.33 ± 7.04 μg/ml) occurred at <1 hr. The AUC_0–∞ (mean ± SD, 12.84±6.62 hr*μg/ml), MRT_inf (mean ± SD, 11.09 ± 9.63 min), T1/2 (harmonic mean ± PseudoSD 5.50 ± 3.80 min), and k/d (mean ± SD, 0.002 ± 0.001 1/min). Significant differences could not be detected between % inhibition of proliferating CD5+ T lymphocytes at any time point (p = .380). No relationship was observed between MPA concentration and % inhibition of proliferating CD5+ T lymphocytes (R = .148, p = .324). Pharmacodynamics do not support the use of MMF in juvenile dogs at the administered dose based on existing therapeutic targets.     

Cover Image,Volume 15, Issue 1

The cover image, by E. Treggiari et al., is based on the Original Article Clinical outcome, PDGFRß and KIT expression in feline histiocytic disorders: a multicentre study, DOI: 10.1111/vco.12142 .

     

Indicators of success for smart law enforcement in protected areas: A case study for Russian Amur tiger (Panthera tigris altaica) reserves

Although considerable conservation resources have been committed to develop and use law enforcement monitoring and management tools such as SMART, measures of success are ill‐defined and, to date, few reports detail results post‐implementation. Here, we present 4 case studies from protected areas with Amur tigers (Panthera tigris altaica) in Russia, in which indicators of success were defined and evaluated at each. The ultimate goal was an increase in tiger numbers to 1 individual/100 km² at each site. We predicted that improvements in law enforcement effectiveness would be followed by increases in prey numbers and, subsequently, tiger numbers. We used short‐term and long‐term indicators of success, including: (i) patrol team effort and effectiveness; (ii) catch per unit effort indicators (to measure reductions in threats); and (iii) changes in target species numbers. In addition to implementing a monitoring system, we focused on improving law enforcement management using an adaptive management process. Over 4 years, we noted clear increases in patrol effort and a partial reduction in threats. Although we did not detect clear trends in ungulate numbers, tiger populations remained stable or increased, suggesting that poaching of tigers may be more limiting than prey depletion. Increased effectiveness is needed before a clear reduction in threats can be noted, and more time is needed before detecting responses in target populations. Nonetheless, delineation of concrete goals and indicators of success provide a means of evaluating progress and weaknesses. Such monitoring should be a central component of law enforcement strategies for protected areas.     

BOARD-INVITED REVIEW: Use of distillers by-products in the beef cattle feeding industry

The ethanol industry is expanding rapidly. This expansion in production of renewable energy also increases production of by-products. These byproducts, primarily distillers grains plus solubles (DGS), are utilized very efficiently by ruminants. When the starch in corn is fermented to produce ethanol, the remaining nutrients (protein, fat, fiber) are concentrated about 3-fold. Whereas DGS is an excellent protein source for ruminants, the large supply and the price relative to corn make DGS an attractive energy source as well. This is especially important with reduced availability and higher price of corn because of demand by the ethanol industry. A meta-analysis of 9 experiments, where various levels of wet DGS were fed to feedlot cattle, shows that wet DGS produced higher ADG and G:F compared with cattle fed corn-based diets without DGS. A similar analysis with dry DGS showed similar type of responses but with less apparent feeding value for dry DGS compared with wet DGS. Metabolism studies suggest the fat in DGS may be partially protected from ruminal degradation leading to greater proportion of unsaturated fatty acids at the duodenum and greater total tract fat digestibility. Both the fat and the undegradable protein in DGS appear to explain some but not all of the greater feeding value of DGS compared with corn. Lower quality roughages may be used in feedlot diets containing wet DGS because of the protein, moisture, and physical characteristics the DGS contains. The feeding value of DGS is greater than dry-rolled corn or high moisture corn; however, the feeding value of DGS appears to be less when fed in finishing diets based on steam-flaked corn than in those based on dry-rolled or high-moisture corn.     

Wild ostrich (<Emphasis Type="Italic">Struthio camelus australis</Emphasis>) reproduction in Orbata,a nature reserve in Tunisia

The aim of the current investigation was to determine wild ostrich reproductive behaviour in Orbata Nature Reserve by observing 16 hens and 28 cocks over a seven-year period. Intense laying commenced in January, one month after the cessation of the rainy season, and 92% of the eggs were produced during the dry season (January to May, peaking in March). Over the seven years, 1,322 eggs were laid in 69 nests, which corresponded to an annual average production of 19.2 ± 9.1 eggs/nest and 11.8 eggs/hen. 24 nests (34.78%) were non-brooded, 17 nests (24.64%) were deserted in the course of incubation, and 28 nests (40.58%) possessed hatched eggs. All the non-incubated nests had egg losses equivalent to 46.6 ± 12.6%. Hatchability success of incubated eggs was 41.9 ± 12.0%. Ostriches tended to dig their nests adjacent to the reserve enclosure which had direct access by road and track, the latter subjecting them to human disturbance and predation. The systematic obstruction of these nests stimulated ostriches to build additional nests within the reserve perimeter. The authors discussed the results recorded in an ostrich flock in relation to the environmental factors (climatic factors, food disponibility and predation) and suggested possibilities for improved wildlife management.     

Dietary incorporation of feedstuffs naturally high in organic selenium for racing pigeons (Columba livia): effects on plasma antioxidant markers after a standardised simulation of a flying effort

Selenium is a trace element of importance for animal health. It is essential for adequate functioning of many enzymes such as, the antioxidant enzyme, glutathione peroxidase, which protects the cell against free radicals. A muscular effort induces a rise in reactive oxygen species production which, in turn, can generate an oxidative stress. Two groups of eight racing pigeons were fed respectively with a diet containing 30.3 (control group) and 195.3 (selenium group) μg selenium/kg diet. The pigeons were submitted to a standardised simulation of a flying effort during 2 h. Blood was taken before and after the effort to measure antioxidant markers and blood parameters related to muscle metabolism. Plasma selenium concentration and glutathione peroxidase activity were significantly higher in the selenium group. There were no significant differences for the other measured parameters. As a consequence of the effort, the pigeons of the selenium group showed a higher increase of glutathione peroxidase activity and a smaller increase of plasma lactate concentration. Variations because of the effort in the other markers were not significantly different between the two groups. It is concluded that the selenium status was improved with the feeding of feedstuffs high in Selenium.     

Meat Science and Muscle Biology Symposium: the influence of extracellular matrix on intramuscular and extramuscular adipogenesis

The extracellular matrix (ECM) and specific ECM components can have a major influence on cell growth, development, and phenotype. The influence of the ECM and ECM components on adipogenesis in vivo and in vitro will be reviewed in this paper. Engelbreth-Holm-Swarm substratum and laminin per se markedly increased attachment, spreading, and hypertrophy of preadipocytes in serum-free primary cultures of porcine adipose tissue stromal-vascular cells. Furthermore, primary cultures of stromal-vascular cells showed that preadipocytes express ECM components after preadipocyte recruitment. Staining for plant lectins, type IV collagen, and laminin in fetal pig adipose tissue demonstrates that adipocyte reactivity for laminin was strong throughout fetal development and was similar for developing adipocytes and vasculature. However, lectin binding and type IV collagen reactivity of blood vessels preceded that for adipocytes. Therefore, these studies indicated that the ECM and in particular laminin may play a critical role in morphological aspects of preadipocyte development. Specific inhibitors and modulators of collagen synthesis have been used to evaluate the role of collagens in the differentiation of bovine intramuscular preadipocytes (BIP) and other preadipocyte cell lines. Triglyceride accretion of BIP cells was inhibited by a general inhibitor of collagen biosynthesis, whereas specific inhibitors or modulators of type IV collagen inhibited 3T3-L1 cell differentiation. Further study revealed that compared with collagens types I to IV, type V and VI collagens have an important and active role in BIP adipogenesis. The growth of intramuscular bovine adipose tissue may be dependent on collagen newly synthesized and organized by the adipocytes per se. The role of extracellular or ECM proteolysis in regulating adipogenesis also will be reviewed in this paper. Many members of the matrix metalloproteinase (MMP) family are expressed by adipocytes, and specific inhibition of MMP-9 greatly reduces adipogenesis in vitro. Possibly, MMP and other proteases regulate turnover of key adipocyte ECM proteins that are involved in the regulation of preadipocyte proliferation and differentiation.     

Effect of maternal seaweed extract supplementation on suckling piglet growth, humoral immunity, selected microflora, and immune response after an ex vivo lipopolysaccharide challenge

The present study was conducted to investigate the effect of maternal dietary supplementation (n = 10 sows/treatment) with seaweed extract (SWE: 0 vs. 10.0 g/d) from d 107 of gestation until weaning (d 26) on neonatal piglet growth, humoral immunity, intestinal morphology, selected intestinal microflora, and VFA concentrations. Furthermore, this study examined the effect of dietary treatment on the immune response after an ex vivo Escherichia coli lipopolysaccharide (LPS) tissue challenge at weaning in a 2 × 2 factorial arrangement. The main factors consisted of sow dietary treatment (SWE or control) and immunological challenge (yes or no). The SWE supplement (10.0 g/d) contained laminarin (1.0 g), fucoidan (0.8 g), and ash (8.2 g) and was extracted from a Laminaria spp. The SWE-supplemented sows had greater colostrum IgA (P < 0.01) and had a trend for greater IgG (P = 0.062) concentrations compared with non-SWE-supplemented sows. Piglets suckling SWE-supplemented sows had greater serum IgG (P < 0.05) concentrations on d 14 of lactation compared with those suckling non-SWE-supplemented sows. Dietary SWE supplementation decreased fecal Enterobacteriaceae populations in sows at parturition (P < 0.05), and piglets suckling SWE-supplemented sows had a decreased colonic E. coli population at weaning (P < 0.01) compared with non-SWE-supplemented sows. Lipopolysaccharide challenge increased the mRNA abundances of the pro-inflammatory cytokines IL-1α and IL-6 (P < 0.01) in ileal tissue and tumor necrosis factor (TNF)-α in colonic (P < 0.01) tissue. There was a treatment × LPS challenge interaction for ileal TNF-α mRNA expression (P < 0.05). Piglets suckling SWE-supplemented sows had greater TNF-α mRNA expression after ex vivo LPS challenge compared with non-SWE-supplemented sows (P < 0.05). However, there was no effect of sow dietary treatment on TNF-α mRNA expression in the unchallenged ileal tissue. Piglet BW at birth and weaning, and small intestinal morphology were unaffected by sow dietary treatment under current experimental conditions. In summary, these results demonstrate an important immunomodulatory role of SWE supplementation characterized by enhanced colostral IgA and IgG concentrations, greater piglet circulatory IgG concentrations on d 14 of lactation, and enhanced TNF-α mRNA expression in the ileum after an ex vivo LPS challenge. These results indicate that SWE supplementation enhanced piglet immune function and colonic microflora at weaning.