Simultaneous application of the vascular endothelial growth factor (VEGF) receptor inhibitor PTK787/ZK 222584 and ionizing radiation does not further reduce the growth of canine oral melanoma xenografts in nude mice

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.     

Developmental temperature affects phenotypic means and variability: A meta‐analysis of fish data

Fishes are sensitive to their thermal environment and face an uncertain future in a warming world. Theoretically, populations in novel environments might express greater levels of phenotypic variability to increase the chance of surviving—and eventually thriving—in the new conditions. Most research on the effect of the early thermal environment in fish species focuses on average phenotypic effects rather than phenotypic variability, but to understand how fishes will respond to rising temperatures we need to consider both the average response of the population, as well as the breadth of individual responses. Here we present the first meta‐analysis on the effects of developmental temperature in fishes. Using data from 43 species and over 6,000 individual fish, we show that a change in developmental temperature induces a significant change in phenotypic means and variability, but differently depending on whether the temperature is increased or decreased. Decreases in temperature (cool environments) showed a significant decrease in phenotypic means and no change in phenotypic variability. Increases in temperature (warm environments) showed a non‐significant increase in phenotypic means and a marginally significant increase in phenotypic variability. Larger increases in temperature saw greater increases in phenotypic variability, but no increase in the mean phenotypic response. Together, our results suggest that fishes exhibit both directed and stochastic developmental plasticity in response to warming temperatures, which could facilitate or accelerate adaptation to a changing environment.     

The effects of cadmium and copper on embryonic and larval development of ide Leuciscus idus L.

The effects of Cd and Cu on embryos and larvae of the ide Leuciscus idus were evaluated. The ide is an European cyprinid fish, natural populations of which tend to decrease. The ide is also used as a bioindicator organism to evaluate water quality. However, sensitivity of ide early developmental stages to heavy metal intoxication is not known. Fish were exposed to Cd or Cu (100 μg/L) during embryonic, larval or both developmental periods. Survival of the embryos, time of hatching, size and quality of newly hatched larvae were evaluated at the end of embryonic period. Correctly developed larvae from the control and Cd or Cu-exposed groups were transferred to clean water, Cd or Cu solutions (100 μg/L) immediately after hatching. Larval development was observed, and the larvae were photographed. Time of yolk sac resorption, onset of active feeding and swim bladder inflation were evaluated, and the measurements were done on body and swim bladder size. The results showed that exposure of embryos to Cd and Cu significantly reduced embryonic survival and increased frequency of body malformations and death in newly hatched larvae and delayed hatching. Exposure to Cd and Cu during larval period reduced larval survival, growth and delayed development (yolk utilization, beginning of active feeding and swim bladder inflation). Cadmium was more toxic to the ide embryos and larvae than copper. Exposures to metals during embryonic period alone caused adverse impact on larval performance even when larval development took place in clean water. However, exposure of embryos to Cu reduced toxic impact of metal on larvae in continuous Cu exposure compared to the non-preexposed fish, but no such an effect occurred in case of Cd exposure. The results show that even a short-term exposure to Cd or Cu during early development of ide may adversely affect recruitment of this species. Among the measured endpoints, quality of newly hatched larvae (frequency of body malformations and larvae dead immediately after hatching) and swim bladder size were the most sensitive to intoxication with both metals. Embryos were more sensitive to Cu intoxication than larvae, while in case of Cd, sensitivity of both stages was similar.     

Pathotypes of <Emphasis Type="Italic">Plasmodiophora brassicae</Emphasis> causing damage to oilseed rape in the Czech Republic and Poland

Winter oilseed rape (Brassica napus) is an important crop in the Czech Republic and Poland. Clubroot disease caused by the pathogen Plasmodiophora brassicae is a serious and still-growing problem for oilseed rape growers in both countries. The aim of this study was to evaluate the pathotype composition of P. brassicae populations from the Czech Republic and Poland, according to the three evaluation systems, and to determine soil inoculum loads for representative fields via traditional end-point PCR as well as quantitative PCR analysis. There were considerable differences between the populations of P. brassicae from both countries, and the number of pathotypes varied depending on the evaluation system and the threshold used to distinguish susceptible vs. resistant plant reactions. This is the first study comparing the effect of different thresholds. Using an index of disease (ID) of 25 % to distinguish susceptible vs. resistant reactions, there was a total of seven pathotypes identified based on the differentials of Williams, five with the system of Somé et al., and 18 with the European Clubroot Differential (ECD) set. However, based on a threshold of 50 %, there were nine pathotypes according to the evaluation system by Williams, four based on the differentials of Somé et al., and 15 with the ECD set. Changing of the thresholds led to the reclassification of some pathotypes. Several pathotypes were common in both countries. High amounts of pathogen DNA were found in many of the field soils analysed by quantitative PCR. There was a weak correlation between soil pH and infestation of P. brassicae for the Polish soils.     

Bioefficacy of Hen Feather Keratin Hydrolysate and Compost on Vegetable Plant Growth

ABSTRACT

The potential of keratin wastes originating from poultry farms in practical application as a valuable organic fertilizer, gives rise to the need for intensive study on their effect on plants. In this study, for the first time there has been examined the influence of hen feather keratin bio-hydrolysate (FKH) and hen feather keratin compost (FKC) on plant growth, and the following features that indicate the plant condition: the leaf chlorophyll content, the activity of phenylalanine ammonia lyase (PAL) and guaiacol peroxidase (GPX) enzymes. The results of pot experiments showed a potential plant growth promoting effect of FKH, applied as a leaf treatment and of FKC manure. Fertilization of tested plants with FKC resulted in significant increase of their fresh weight. There was no effect on plant biomass after FKH treatment. The stimulating effect on plant physiology was expressed by decreased PAL activity after FKC treatment, and enhanced GPX activity, after FKH and FKC treatment. The application of FKC as a manure gave better effects for the plant condition expressed by the activity of PAL and GPX in comparison with FKH spraying. The chlorophyll content did not prove to be an efficient parameter to evaluate the impact of FKH or FKC on white cabbage, tomato, and maize plant. However, a significant increase in the leaf chlorophyll a, b, and a+b concentration was observed in cucumber plant after FKC treatment. Among the tested plants, the cucumber has shown the most profitable effect of feather compost on plant growth.     

Changes of redox and pH conditions in a flooded soil amended with glucose and manganese oxide or iron oxide under laboratory conditions

The changes of Eh and pH in soil suspension (Ah-horizon of a Mollic Gleysol) and Mn²⁺ or Fe²⁺ concentrations in the equilibrium soil solution at different levels of glucose (0%, 0.5% and 1%) and MnO₂ (0%, 0.025%, 0.05% and 0.1%) or Fe₂O₃ (0%, 0.025%, 0.05% and 0.1%) were examined. It was found that the degree of Mn- and Fe-reduction in soil depends mainly on the presence and the amount of an easily decomposable carbon source and to a minor degree on the content of native or added forms of MnO_O2 or Fe₂O₃ in the soil. Theoretical relationships between the water soluble manganese and iron and the Eh and pH values have been verified, when the observed initial drop of Eh was eliminated. It was found that the water soluble manganese content was described best by the Mn₂O₃/Mn²⁺ redox system, and that of iron by the Fe₃ (OH)₃/Fe²⁺ system.     

A complication probability study for a definitive‐intent,moderately hypofractionated image‐guided intensity‐modulated radiotherapy protocol for anal sac adenocarcinoma in dogs

Previous trials showed the importance of administering radiation therapy (RT) with small doses per fraction in canine pelvic tumours to maintain acceptable toxicity levels. With increased accuracy/precision of RT, namely intensity‐modulated RT (IMRT), this approach might be challenged. Theoretical toxicity calculations for a new definitive‐intent moderately hypofractionated RT protocol for canine anal sac adenocarcinomas (ASAC) were performed, focussing on the risk of toxicity in pelvic organs at risk (OAR). Computed tomography datasets of 18 dogs with stage 3b ASAC were included. Re‐planning with margins for daily image‐guidance/IMRT was performed and a new protocol isoeffective to previously described definitive‐intent protocols was computed. Dose‐volume information were derived from individual plans and used for normal tissue complication probability (NTCP) computations. A 12 × 3.8 Gy protocol was computed for risk estimation. Tumour volumes ranged from 27.9 to 820.4 cm³ (mean 221.3 cm³ ± 188.9). For late rectal toxicity/bleeding ≥grade 2, median risk probability was 2.3% inter quartile range (IQR: 5.9; 95% confidence interval (CI): 1.2, 8.4) (rho = 0.436) and 3.4% (IQR: 0.96; 95%CI: 3.1, 4.0) (rho = 0.565), respectively. Median late toxicities in urinary bladder, kidneys and small bowel were <1%, except in one kidney. Myelopathy/myelonecrosis had a median risk probability of 4.1% (IQR: 23.5; 95%CI: 2.1, 25.2) (rho = 0.366) and 5.6% (IQR: 13.5; 95%CI: 3.1, 14.1) (rho = 0.363), respectively. However, graded risk showed a probability estimate for late spinal cord toxicity of ≥5% in 8/18 patients. The daily‐imaging IMRT 12 × 3.8 Gy protocol for canine ASAC seems tolerable for most cases, even in advanced disease. Theoretical dose computations serve as estimate, but are safe measures before implementing new protocols into clinical use.     

Irradiation of brain tumors in dogs with neurologic disease

Radiation therapy is the treatment of choice for many primary canine brain tumors. The radiation dose tolerated by surrounding healthy brain tissue can be a limiting factor for radiation treatment and total dose as well as fractionation schedules, and volume effects may play a role in the outcome of patients undergoing radiation therapy. The purpose of this retrospective study was to evaluate the efficacy of radiation therapy in dogs with brain tumors that showed signs of neurologic disease. Forty-six dogs with brain tumors were included in the analysis. In 34 dogs, computer-generated treatment plans were available, and dose-volume data could be obtained. The totally prescribed radiation therapy doses ranged from 35 to 52.5 Gy (mean = 40.9 [SD +/- 2.91) applied in 2.5- to 4-Gy fractions (mean = 3.2). The median overall survival time calculated for deaths attributable to worsening of neurologic signs was 1,174 days (95% confidence interval [CI], 693-1,655 days). Assuming that all deaths were due to disease or treatment consequences, the median survival time was 699 days (95% CI, 589-809 days). No prognostic clinical factors such as the location or size of the tumor or neurologic signs at presentation were identified. With computerized treatment planning and accurate positioning, high doses of radiation (> 80% of the total dose) could be limited to mean relative brain volumes of 35.3% (+/- 12.6). These small volumes may decrease the probability of severe late effects such as infarction or necrosis. In this study, very few immediate or early delayed adverse effects and no late effects were noted, and quality of life was good to excellent.