Inhibition of telomerase in canine cancer cells following telomestatin treatment

Telomere shortening in normal somatic cells has been proposed as a major barrier to unlimited cellular proliferation. Telomerase is an enzyme capable of maintaining telomere length, and thus bypassing this barrier. In human beings, telomerase activity is restricted to cancer cells and cells of stem or germ cell lineages. Dogs represent a potentially useful clinical model for the development of telomerase‐based therapies because telomerase activity is also restricted to cancer cells and stem cells in this species. We examined the ability of telomestatin to inhibit telomerase activity in telomerase‐positive D17 and CMT7 canine cancer cell lines. At a concentration of 2 μM, telomestatin treatment resulted in a decrease in telomerase activity, telomere shortening, growth inhibition and apoptosis in telomerase‐positive cancer cells. These effects were not seen in telomerase‐negative skin fibroblasts or negative controls. These results confirm that telomestatin specifically inhibits telomerase activity in canine cancer cells and strengthens the usefulness of dogs as a model for testing telomerase‐based therapies.     

Effects of steam-treated rice straw feeding on growth,digestibility, and plasma volatile fatty acids of goats under different housing systems

In order to use rice straw as forage in livestock feeding, the effects of steam-treated rice straw (at 15.5 kgf/cm² for 120 s) feeding on growth performance, plasma volatile fatty acid profile, and nutrient digestibility of goats were determined. Twenty male goats (18.69?±?0.34 kg) were used in an 84-day trial. The goats were divided into four groups of five goats each to receive steam-treated (STRS) or untreated (UTRS) rice straw diet under closed house (CH) and open house (OH) systems. The results revealed that the goats fed with STRS had significantly higher dry matter (DM), organic matter (OM), crude protein (CP), neutral detergent fiber (NDF), and acid detergent fiber (ADF) digestibility; similarly, the average daily weight gain and feed conversion ratio were higher for STRS groups under both CH and OH systems than those for UTRS. The plasma protein and insulin in STRS and cholesterol in UTRS groups was higher (P?P?>?0.05) at 30 days. The plasma amylase, lipase, T₃, T₄ and glucagon at 30 and 60 days were not different (P?>?0.05) among the groups. The plasma acetate, propionate, butyrate, and total volatile fatty acid were higher (P?P?>?0.05) on these parameters. It could be concluded that steam treatment of rice straw at 15.5 kgf/cm² for 120 s increased apparent nutrient digestibility, hence increased the growth and feed efficiency of growing goats.     

早春短命植物绵果荠愈伤组织诱导相关因素研究

绵果荠是分布在新疆北部准噶尔荒漠中的十字花科一年生早春短命植物。本研究为探讨绵果荠愈伤组织诱导条件,以无菌苗子叶为外植体,研究了不同苗龄、培养基种类、蔗糖浓度和培养条件对愈伤组织的诱导及其生长的影响。结果表明,1)愈伤组织诱导的最佳条件为:苗龄14 d、培养基为MS+1.0 mg/L IBA+0.1 mg/L BAP、含糖量3%、温度25℃和光照为黑暗。2)愈伤组织生长的适宜条件是光照16 h/d和温度25℃。     

Impact of Endocrine‐Disrupting Chemicals on Reproductive Function in Zebrafish (Danio rerio)

The prevalence of endocrine‐disrupting chemicals (EDCs) in the aquatic environment has been associated with the wide detection of alterations in the development and physiology of vertebrates. Zebrafish, as a model species, has been extensively used in toxicological research. In this review, we focus on recent published evidence of the harmful effects of EDCs on reproductive function in zebrafish, including skewed sex ratio, immature gonads, diminished sexual behaviour, decreased sperm count, reduced spawning and fertilization. These impairments mostly result from disruption to sex‐steroid hormones induced by endocrine disruptors. We also discuss other effects of exposure to EDCs. In EDC exposure research, despite incomplete assessments of altered gonad histopathology and sexual behaviour, these present potential effective biomarkers or pathways for evaluating the reproductive function in zebrafish on EDC exposure. To date, the pernicious effects of some EDCs on the reproductive performance in laboratory zebrafish are well understood; however, similar alterations remain for further determination in wild‐type fish and more kinds of EDCs. More studies should be performed under established scientific regulatory criteria to investigate the impact of EDCs on reproduction in zebrafish. Moreover, further research is required to explain the definite mechanism of sexual differentiation, which helps in understanding the shift of sexual phenotype with EDC exposure.     

Pharmacokinetics of toltrazuril and its metabolites in pregnant and nonpregnant ewes and determination of their concentrations in milk,allantoic fluid,and newborn plasma

The objectives of this study were to determine the pharmacokinetics of toltrazuril and its metabolites in pregnant and nonpregnant ewes following a single oral dose and to determine the plasma concentrations of these compounds in milk, allantoic fluid, and newborn plasma. Eighteen healthy ewes were randomly divided into three groups (n = 6 each): pregnant ewes at 12–13 weeks of gestation (group A), nonpregnant ewes (group B), and pregnant ewes at 1–2 weeks before expected lambing date (group C). Ewes in all groups received a single oral dose of toltrazuril at 20 mg/kg body weight. In groups A and B, blood samples were collected at 1, 3, 5, 7, 9, 12, 15, 18 hr, every 6 hr to day 3, every 12 hr to day 7 and thereafter every 24 hr to day 14 post-toltrazuril administration. In group C, parturition was induced 24–36 hr after toltrazuril administration then milk, allantoic fluid, and newborn plasma samples were collected immediately after birth. Drug metabolites were assayed using ultra high-performance liquid chromatography–ultraviolet detection method (UHPLC-UV). The maximum concentration (C_max), area under the plasma concentration-time curve (AUC_0–t), AUC to 24 and 48 hr (AUC_0–24), and (AUC_0–48) were significantly higher in pregnant ewes. Longer apparent half-life (T_1/2), significantly higher apparent volume of distribution (Vd/F) and total clearance (Cl/F) were observed in nonpregnant ewes. The time to maximum plasma concentration (T_max), mean residence time (MRT) and elimination rate constant (K_el) were similar in both groups. The AUC_0–24 and AUC_0–48 were significantly higher in nonpregnant ewes. The AUC_0–t was significantly higher in pregnant ones. The ratio of plasma toltrazuril concentrations in ewes and toltrazuril concentrations in newborn lambs' plasma, allantoic fluid, and milk were 68%, 2.3%, and 5.3%, respectively. Results of this study showed that toltrazuril is well absorbed after a single oral dose in ewes with widespread distribution in different body tissues.     

Telomeres and telomerase: Biological and clinical importance in dogs

In recent years in human oncology the enzyme telomerase has emerged as an ideal target for cancer therapy. This has led to the assessment of telomerase in cancers in companion animals, mainly dogs and these studies confirm that in dogs, like humans, telomere maintenance by telomerase is the primary mechanism by which cancer cells overcome their mortality and extend their lifespan. This review aims to provide an introduction to the biology of telomeres and telomerase and to discuss some of the telomere/telomerase directed therapeutic methodologies currently under development which may be of benefit to the canine cancer patient.     

Preparation of controlled-release formulations of 14C-labelled thiobencarb herbicide and study of their environmental behaviour

Controlled-release formulations of ¹⁴C-labelled thiobencarb herbicide were prepared in calcium alginate using kaolin as an inexpensive filler. The rates of release of the herbicide from these and from a commercial granular formulation were studied in static distilled water contained in open and closed vessels. The rate of release of the herbicide was much higher from the commercial formulation than from the controlled-release formulations. Increasing the proportion of kaolin to calcium alginate in controlled-release formulations reduced the rate of release of the herbicide. There was a significant loss of thiobencarb-related radioactivity from the water solution when the vessels containing the solutions were left uncovered and exposed to light. The loss of the herbicide seemed to be due to degradation and evaporation.     

Equine sarcoids: Bovine Papillomavirus type 1 transformed fibroblasts are sensitive to cisplatin and UVB induced apoptosis and show aberrant expression of p53

Bovine papillomavirus type 1 infects not only cattle but also equids and is a causative factor in the pathogenesis of commonly occurring equine sarcoid tumours. Whilst treatment of sarcoids is notoriously difficult, cisplatin has been shown to be one of the most effective treatment strategies for sarcoids. In this study we show that in equine fibroblasts, BPV-1 sensitises cells to cisplatin-induced and UVB-induced apoptosis, a known cofactor for papillomavirus associated disease, however BPV-1 transformed fibroblasts show increased clonogenic survival, which may potentially limit the therapeutic effects of repeated cisplatin treatment. Furthermore we show that BPV-1 increases p53 expression in sarcoid cell lines and p53 expression can be either nuclear or cytoplasmic. The mechanism and clinical significance of increase/abnormal p53 expression remains to be established.