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The 5‐lipoxygenase inhibitor tepoxalin induces oxidative damage and altered PTEN status prior to apoptosis in canine osteosarcoma cell lines 
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下载免费PDF全文 J. P. Loftus D. Cavatorta J. J. Bushey C. B. Levine C. S. Sevier J. J. Wakshlag 《Veterinary and comparative oncology》2016,14(2):e17-e30
The 5‐lipoxygenase (5‐LOX) inhibitor tepoxalin has been shown to slow canine osteosarcoma (OSA) tumour xenografts growth, yet the mechanisms are poorly elucidated. Further examination of tepoxalin in canine OSA cell lines shows that tepoxalin treated cells undergo apoptosis through caspase‐3 activation and annexin staining. Interestingly, apoptosis is superseded by an increase in reactive oxygen species (ROS), as measured by activation of dihydrorhodamine 123 and mitosox. This increase in ROS appears to be related to the 5‐LOX inhibitor regardless of cellular 5‐LOX status, and was not observed after treatment with the tepoxalin metabolite RWJ20142. Additionally, 5‐LOX inhibition by tepoxalin appears to increase phosphatase and tensin (PTEN) homolog activity by preventing its alkylation or oxidation. PTEN modification or inhibition allows phosphoinositide‐3 (PI3) kinase activity thereby heightening activation of protein kinase B (AKT) phosphorylation. Our data suggest that off target oxidation and LOX inhibition play roles in the apoptotic response. 相似文献
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RR Moura ES Lopes‐Junior DIA Teixeira IA Serova LE Andreeva LM Melo VJF Freitas 《Reproduction in domestic animals》2010,45(5):e101-e106
The objective of this study was to examine the effect of donor breed on pronuclear‐stage embryo yield to be used for DNA microinjection in a transgenesis goat program. Twelve Canindé and twelve Saanen goats were heat synchronized using a progestagen‐cloprostenol treatment. Forty‐eight hours before the sponge removal, superovulation was induced with a total administration of 4.4 mg/kg bodyweight NIH‐FSH‐P1, given twice daily in decreasing doses over 3 days. In addition, goats received 100 μg of GnRH and they were hand‐mated at 36 and 48 h after progestagen removal. Embryo recovery was performed by oviduct flushing at 72 h after sponge removal. Embryos were microinjected with a DNA construct and noticeable swelling of the nuclei was the criterion for successful microinjection. The total diameter, cytoplasm diameter, zona pellucida thickness and pronuclei diameter were measured for each microinjected embryo. A higher (p < 0.05) percentage of fertilized ova was observed in Canindé (89.9%) than Saanen (36.2%) goats. In addition, Canindé donors produced a higher percentage of pronuclear embryos when compared with Saanen: 72.5% vs 20.6% (p < 0.05), respectively. Successful microinjection was verified in 96.7% and 73.3% of times in Canindé and Saanen embryos, respectively (p < 0.05). Significant differences were observed for all morphometric parameters except for cytoplasm diameter. In conclusion, under our study experimental conditions, Canindé were more efficient than Saanen goats concerning the pronuclear embryo yield and manipulation. The use of Canindé goats in transgenesis programs could be increase the interest in their breeding and could be contribute to saving them from extinction. 相似文献
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JR BUDDLE AR MERCY SZ SKIRROW F. MADEC RR NICHOLLS 《Australian veterinary journal》1997,75(4):274-281
Objective To determine in Australian pig herds the accuracy of French protocols for risk factor assessment.
Procedure Data on health indicators and risk factors were collected for three syndromes, 'pre-weaning diarrhoea', 'post-weaning diarrhoea' and 'respiratory problems', using the French protocols. The protocols were used on 118 occasions in 32 Western Australian pig herds during 3 years (1988 to 1991).
Results There was a wide variation in pre-weaning performance, for example growth rate was 107 to 273 g/day (< 200 g/day in 33% of herds). Respiratory lesions at weaning were associated with poor pre-weaning performance. Post-weaning (21 days after weaning) growth rate was 114 to 408 g/day (< 250 g/day in 54% of herds). In the grower herds, 91% of herds had pneumonia, and growth rate was 439 to 625 g/day (< 550 g/day in 54% of herds). Pleurisy as well as pneumonia was associated with reduced growth rate. The risk factor most closely associated with respiratory health status was air volume per pig.
Conclusion Risk factors were most accurate at predicting the health status in post-weaning problems. A weaning weight of at least 7.9 kg and weaning age of 30 days optimised weaner performance. Stocking densities and shed designs providing at least 3 m3 air volume and 0.6 m2 floor space per pig throughout the growing phase should be considered for an improved respiratory health status. Australian pig sheds often do not provide a satisfactory environment for optimum health. The technique of risk factor assessment as an aid to the maintenance of health in pig herds is applicable in Australia, but further research is necessary to determine the most important Australian risk factors. 相似文献
Procedure Data on health indicators and risk factors were collected for three syndromes, 'pre-weaning diarrhoea', 'post-weaning diarrhoea' and 'respiratory problems', using the French protocols. The protocols were used on 118 occasions in 32 Western Australian pig herds during 3 years (1988 to 1991).
Results There was a wide variation in pre-weaning performance, for example growth rate was 107 to 273 g/day (< 200 g/day in 33% of herds). Respiratory lesions at weaning were associated with poor pre-weaning performance. Post-weaning (21 days after weaning) growth rate was 114 to 408 g/day (< 250 g/day in 54% of herds). In the grower herds, 91% of herds had pneumonia, and growth rate was 439 to 625 g/day (< 550 g/day in 54% of herds). Pleurisy as well as pneumonia was associated with reduced growth rate. The risk factor most closely associated with respiratory health status was air volume per pig.
Conclusion Risk factors were most accurate at predicting the health status in post-weaning problems. A weaning weight of at least 7.9 kg and weaning age of 30 days optimised weaner performance. Stocking densities and shed designs providing at least 3 m
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PE Sbardella RR Ulguim DL Fontana CV Ferrari ML Bernardi I Wentz FP Bortolozzo 《Reproduction in domestic animals》2014,49(1):59-64
The study evaluated the reproductive performance of primiparous sows submitted to post‐cervical insemination (PCAI) compared with cervical artificial insemination (CAI). Difficulty with catheter introduction, the occurrence of bleeding or semen backflow during insemination, and volume and sperm cell backflow up to 60 min after insemination were also evaluated. Sows were homogenously distributed, according to body weight loss in lactation, lactation length, weaned piglets, weaning‐to‐oestrus interval and total born in previous farrowing, in two treatments: PCAI (n = 165) with 1.5 × 109 sperm cells in 45 ml (2.4 ± 0.04 doses per sow) and CAI (n = 165) with 3 × 109 sperm cells in 90 ml (2.5 ± 0.04 doses per sow). During PCAI, sows were inseminated in the absence of boars. Transabdominal real‐time ultrasonography was performed at oestrus onset, immediately before the first insemination and at 24 h after last insemination. There was no difference (P > 0.05) between treatments in farrowing rate (91.5% × 89.1%) and litter size (12.5 × 11.9 piglets born, respectively for PCAI and CAI sows). Successful passage of the intrauterine catheter in all the inseminations was possible in 86.8% (165/190) of sows initially allocated to PCAI treatment. Difficulty of introducing the catheter in at least one insemination did not affect the reproductive performance of PCAI sows (P > 0.05). Bleeding during insemination did not affect (P > 0.05) the farrowing rate in both treatments, but litter size was reduced in CAI and PCAI sows (P ≤ 0.06). Percentage of spermatozoa present in backflow within 1 h after insemination was greater in CAI than PCAI sows (P < 0.01). More than 85% of primiparous sows can be successfully post‐cervical inseminated with doses containing 1.5 × 109 sperm cells in the absence of the boar during insemination without impairing the reproductive performance. 相似文献
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Wakshlag JJ Cooper BJ Wakshlag RR Kallfelz FA Barr SC Nydam DV Dimauro S 《American journal of veterinary research》2004,65(4):480-484
OBJECTIVE: To perform respiratory chain enzymatic activity assays on canine skeletal muscle biopsy specimens and establish reference range values of skeletal muscle enzyme activities for dogs. SAMPLE POPULATION: Biopsy specimens from the vastus lateralis muscle were obtained from 24 dogs (8 sexually intact males and 14 sexually intact females) ranging from 15 months to 6 years of age. PROCEDURE: Mean values of citrate synthase, cytochrome-c oxidase, succinate dehydrogenase, succinate dehydrogenase-cytochrome-c reductase, nicotinamide adenine dinucleotide (NADH) dehydrogenase, and NADH dehydrogenase-cytochrome-c reductase activities were established by use of 6 standard spectrophotometric assays for respiratory chain enzyme analysis. RESULTS: Compared with published data for skeletal muscle enzyme activities in humans, skeletal muscle enzyme activities in dogs were 2- to 4-fold higher. Additionally, citrate synthase activity, a marker for mitochondrial volume, was positively correlated with age in dogs, suggesting that mitochondrial volume increases with age, although no apparent change in respiratory chain enzymatic activity with an increase in age was found. CONCLUSIONS AND CLINICAL RELEVANCE: Reference range values for skeletal muscle enzyme activities of dogs are needed to accurately interpret results of respiratory chain enzymatic activity assays. During investigation of metabolic myopathies, if skeletal muscle biopsy specimens are evaluated for respiratory chain enzyme kinetics, they should be performed and evaluated in concert with skeletal muscle biopsy specimens from clinically normal animals of the same species. 相似文献
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Canine osteosarcoma is an insidious disease with few effective treatment modalities; therefore, use of pharmacologic intervention to improve mortality or morbidity is constantly sought. The use of cyclooxygenase enzyme inhibitors has been an area of interest with limited efficacy based on retrospective examination of tumor expression and in vivo cell proliferation models. Recently, examination of dual cyclooxygenase and 5-lipoxygenase inhibitors in human and canine oncology suggests that 5-lipoxygenase inhibitors may be an effective approach in vitro and during tumor induction in rodent models. Therefore, the authors decided to examine 5-lipoxygenase expression in primary canine osteosarcoma samples and have shown that approximately 65% of osteosarcomas label positive for cytoplasmic 5-lipoxygenase. Further examination of a cell culture and xenograft model shows similar 5-lipoxygenase expression. Surprisingly, a canine 5-lipoxygenase inhibitor (tepoxalin) significantly reduced cell proliferation at physiologic doses in vitro and diminished xenograft tumor growth in nude mice, suggesting that further investigation is needed. Traditionally, 5-lipoxygense leads to production of lipid mediators, such as leukotriene B(4) and 5-oxo-eicosatetraenoic acid, which, when added back to the media of tepoxalin-treated cells, did not recover cell proliferation. The lack of nuclear staining in primary and xenografted tumors and the lack of response to eicoasanoids suggest that lipid mediator production is not the primary means by which tepoxalin acts to alter proliferation. Regardless of the mechanisms involved in retarding cell proliferation, future investigation is warranted. 相似文献
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AMJ McFadden BD McFadden GF Mackereth RR Clough L Hueston B Gradwell 《New Zealand veterinary journal》2013,61(2):116-120
AIM: To determine if cattle exposed to the southern saltmarsh mosquito (SSM), Aedes camptorhynchus, in the Thames-Coromandel district of New Zealand had been exposed to Ross River virus (RRV). METHODS: A purposive sampling design was used to test cattle from seven farms located in close proximity to four sites infested with A. camptorhynchus in the Thames-Coromandel district. Sera from 207 cattle were tested for antibodies to RRV, using an ELISA and confi rmatory virus neutralisation test (VNT) as the gold standard. RESULTS: All 207 cattle tested negative for antibodies to RRV using the ELISA and VNT. CONCLUSIONS: This study found no evidence of exposure to RRV in cattle in locations in the Thames-Coromandel district of New Zealand where populations of SSM were present. 相似文献
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PB Fernandes KO Marques FR de Araujo Neto DP de Oliveira NA Hurtado‐Lugo RR Aspilcueta‐Borquis H Tonhati 《Reproduction in domestic animals》2016,51(3):428-434
Because of the importance of reproduction in stock breeding systems, it is necessary to find selection criteria that increase reproductive efficiency. The aim of this study was to estimate genetic parameters for the probability of conception on first service (PROB) in Murrah heifers, and its association with other traits of economic interest [age at first calving (AFC), service period, calving interval and milk yield at 270 days], with the purpose of evaluating their use as selection criteria. Reproductive information and first lactation records of 1200 Murrah heifers were used to perform two‐trait analyses between PROB and the other characteristics. Bayesian inference was used to estimate the variance components, considering PROB as threshold and the other as linear factors. The results demonstrate that this trait has heritability of 0.15, indicating the possibility of a genetic gain by using it for selection. With respect to the genetic correlation estimates, the only high‐magnitude association was with AFC (?0.899), which is the current criterion indicating sexual precocity of females. In the light of the parameters estimated, the first‐service pregnancy rate is an alternative for indication of sexual precocity, although presenting a smaller genetic gain than the current standard AFC. Nevertheless, additional research should be conducted regarding this trait to assess the economic importance of its use in dairy buffalo production systems. 相似文献