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PTK787/ZK 222584 is an inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinases. In this study, the effectiveness of PTK787/ZK 222584 and radiation on canine oral melanoma xenografts was assessed. Xenografts were treated with radiotherapy (4x6Gy), or with PTK787/ZK 222584, or with a combination of both. Treatment efficacy was assessed using a tumour growth delay assay, serial power Doppler and pO(2) measurements during and after therapy. There was a significant growth delay for the group treated with radiation alone and for the combined treatment group. However, tumour growth delay was similar in both groups. Tumours were hypoxic before irradiation and no significant re-oxygenation occurred during therapy. In all tumours, vascularity and perfusion were significantly lower at the end of the study but no significant differences in perfusion, vascularity and oxygenation status were observed between and within treatment groups. The combination of PTK787/ZK 222584 and radiotherapy did not perform better than radiotherapy alone in this model.  相似文献   
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OBJECTIVE: The effect of sedation on gastric emptying was evaluated in six ponies by monitoring serum concentrations of acetaminophen (AP) after intragastric administration. EXPERIMENTAL DESIGN: Prospective randomized experimental study. ANIMALS: Six adult ponies, 135 to 275 kg. METHODS: Fifteen minutes after the intravenous administration of xylazine (1 mg/kg), butorphanol (0.05 mg/kg), acepromazine (0.05 mg/kg) or saline, ponies were given AP (20 mg/kg in 350 mL water) by stomach tube. Blood for AP analysis was collected at baseline and 15, 30, 45, 75, 90, 105, and 120 minutes after AP administration. The time (Tmax) to reach peak serum concentration (Cmax), and the area under the AP serum concentration versus time curve (AUC) were determined for each treatment group. RESULTS: Tmax was 31 mins in the control group, and this increased significantly (P<.05) after sedation. Cmax decreased (P<.05) after xylazine administration, and AUC decreased (P<.05) after acepromazine. CONCLUSIONS: This study indicated that sedation has a significant effect on the gastric emptying rate of a liquid in ponies.  相似文献   
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European nase (Chondrostoma nasus) is a specialist riverine fish, characterised by a complex life cycle making it vulnerable to habitat degradation. Recent findings indicate that, analogously to salmonids, the interstitial zone quality may pose a serious bottleneck for successful recruitment of this species. In this study, nase eggs were exposed to different substrate qualities. First, standardised substrate mixtures with differing fine sediment additions were used. Second, we tested different homogenous gravel fractions for their influence on egg development and emergence success. In both setups, substrate composition significantly affected emergence success, timing of emergence and larvae size at emergence. In the substrate mixtures, emergence was most successful in substratum with no fine sediment addition (98%) and decreased to 55% in substratum with 20% fine sediment addition. Emergence was most successful in the coarsest fraction (93%) and decreased to 47% in the finest fraction. Over all treatments, the time between hatching and emergence from substrate differed by up to 156 degree days, thereby indicating that free embryos of nase use the shelter of the interstitial zone for early ontogeny. These results suggest that a loose and porous stream bed can positively contribute to the development success of eggs and larvae and thereby potentially improve the recruitment of nase populations. It is thus important to consider the substrate and interstitial conditions in the conservation and restoration management of this rheophilic cyprinid.  相似文献   
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A series of growth, feed stability and consumption trials were conducted to evaluate the efficacy of salmon by‐product in practical diets for Pacific white shrimp, Litopenaeus vannamei. This included a salmon by‐product meal (Salmon meal: SM) and a silage hydrolysate (hydrolysed salmon meal: HSM). The basal diet containing 120 g/kg SM was incrementally replaced (0. 25, 50, 75, 100%) by HSM to produce five test diets used in two trials. A sixth diet was included which evaluated gelatin supplementation (trial 1) or pH neutralization (trial 2). In trial 1, each diet was produced using two processing conditions (laboratory extruded and formed with meat grinder) and offered to shrimp in a clear water system. The results demonstrate that up to 50% of the SM can be used to replace with HSM; however, further increases resulted in reduced performance of shrimp. The addition of gelatin reduced leaching but there was limited effect of processing on leaching. There were no detectible effects of pH adjustment of the diets. Results indicated that the growth performance of shrimp has not influenced by HSM up to 60 g/kg to replace 50% of the SM in practical diets; however, higher levels resulted in significant decrease in performance.  相似文献   
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Florida pompano Trachinotus carolinus is an important species in which the essentiality of taurine has been demonstrated, yet a quantitative requirement has not been estimated. Two experiments were conducted where a combined twelve diets were formulated with graded levels of taurine (ranging 1.6–41.6 g/kg dry matter) and fed to juvenile pompano (initial weight 7.73 and 4.37 g in trial 1 and 2, respectively). Dose responses were observed in terms of growth, feed efficiency and whole‐body taurine content, but there was no effect on survival. Several regression models were evaluated to determine the most appropriate one to draw conclusions from. A 4‐parameter saturation kinetic model was selected to model feed efficiency, while a 5‐parameter saturation kinetic model fitted the growth data (as thermal‐unit growth coefficient, TGC). A broken‐quadratic model served to estimate a breaking point in the whole‐body taurine content, although it also showed that whole‐body taurine kept increasing even at dietary levels in far excess of the requirement. The dietary taurine requirement was estimated at 2.5 g/kg (2.0–3.3 g/kg, 95% CI, dry matter basis) based on feed efficiency, while TGC was maximized at levels between 4.9 and 31.4 g/kg dietary taurine.  相似文献   
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Sustainability indices are proliferating, both to help synthesize scientific understanding and inform policy. However, it remains poorly understood how such indices are affected by underlying assumptions of the data and modelling approaches used to compute indicator values. Here, we focus on one such indicator, the fisheries goal within the Ocean Health Index (OHI), which evaluates the sustainable provision of food from wild fisheries. We quantify uncertainty in the fisheries goal status arising from the (a) approach for estimating missing data (i.e., fish stocks with no status) and (b) reliance on a data‐limited method (catch‐MSY) to estimate stock status (i.e., B/BMSY). We also compare several other models to estimate B/BMSY, including an ensemble approach, to determine whether alternative models might reduce uncertainty and bias. We find that the current OHI fisheries goal model results in overly optimistic fisheries goal statuses. Uncertainty and bias can be reduced by (a) using a mean (vs. median) gap‐filling approach to estimate missing stock scores and (b) estimating fisheries status using the central tendency from a simulated distribution of status scores generated by a bootstrap approach that incorporates error in B/BMSY. This multitiered approach to measure and describe uncertainty improves the transparency and interpretation of the indicator and allows us to better understand uncertainty around our OHI fisheries model and outputs for country‐level interpretation and use.  相似文献   
50.
The calcium channel and the ‘calcium release channel’ of muscle membrane of the cockroach Periplaneta americana have been characterized. Biological assays with calcium channel blockers and ryanodine on different insects and acari revealed pronounced insecticidal effects with ryanodine, but not with calcium channel blockers, at concentrations between 0·1 and 300 μg ml−1. Skeletal muscle membranes derived either from the tubular network or from the sarcoplasmatic reticulum of P. americana were characterized with respect to the binding of the dihydropyridine (DHP) [3H]isradipine (PN 200-110), the phenyl-alkylamine [3H]verapamil and the alkaloid [3H]ryanodine. Preliminary binding studies with the benzothiazepine [3H]diltiazem suggest a low-affinity binding site with a IC50 value of 3·3 μM . All binding sites tested were sensitive to treatment with proteinase K. Optimal conditions for binding of the radioligand ryanodine revealed the highest specific binding at pH 8 and at calcium chloride concentrations between 100 and 500 μM . EGTA at 10 μM abolished 95% of the ryanodine binding. Binding studies with calcium channel binding sites revealed a pronounced effect of low Ca2+ concentrations on specific isradipine binding, whereas verapamil and diltiazem binding were only reduced by the presence of 200 μM EGTA. With respect to high Ca2+ concentrations, specific binding of diltiazem, isradipine and verapamil was reduced by 73, 40 and 20%, respectively, at 5 mM Ca2+. Radioligand binding experiments showed high-affinity binding sites for ryanodine and isradipine. KD values of 0·95 nM (Bmax=550 fmol mg−1 protein) and 0·75 nM (Bmax=213 fmol mg−1 protein) were determined respectively. A lower-affinity binding site was identified in binding studies with verapamil (KD=7·4 nM and Bmax=27 fmol mg−1 protein). [3H]isradipine displacement studies with several dihydropyridines revealed the following ranking of affinity: nitrendipine>isradipine>Bay K8664≪nicardipine. Displacement of [3H]verapamil binding by effectors of the phenylalkylamine binding site showed that bepridil and S(-)verapamil had the highest affinities of the compounds tested followed by (±)verapamil, nor-methylverapamil and R(+)verapamil.  相似文献   
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