FEASIBILITY FOR USING HYPOFRACTIONATED STEREOTACTIC VOLUMETRIC MODULATED ARC RADIOTHERAPY (VMAT) WITH ADAPTIVE PLANNING FOR TREATMENT OF THYMOMA IN RABBITS: 15 CASES

Thymoma is a relatively common tumor in rabbits. Treatment with surgery, radiation therapy, and chemotherapy alone or in combination has been reported with varying outcomes. Stereotactic volumetric modulated arc radiotherapy delivered in a hypofractionated manner allows high doses of radiation to be delivered to the target volume while allowing sparing of adjacent critical structures. This therapy is ideally suited for thymomas in rabbits given their size, the difficulty of multiple anesthesia episodes and the complexity of the radiotherapy plans required due to the tumor's proximity to the heart, lungs, and mediastinal structures. Fifteen rabbits with thymoma were prospectively recruited for this observational, single institution, single arm clinical study. All rabbits were imaged with both computed tomography (CT) and magnetic resonance imaging (MRI). A total dose of 40 Gy in six fractions was delivered using a single arc over an 11‐day period with repeat CT simulation done every other fraction for adaptive planning. Follow‐up evaluation was done through repeat CT and MRI imaging and revealed complete responses using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Two rabbits had died at 618 and 718 days, 10 were alive and three were lost to follow‐up. Observed acute and late effects were graded according to the Veterinary Radiation Therapy Oncology Group (VRTOG) criteria and were found to be minimal.     

Large granular lymphocytosis in a cynomolgus macaque (Macaca fascicularis) with a subclinical Trypanosoma cruzi infection

A 5.25-year-old cynomolgus macaque (Macaca fascicularis) was found to have a marked leukocytosis due to a lymphocytosis on routine quarantine laboratory data prior to inclusion in a preclinical research study. The majority of lymphocytes were characterized as intermediate to large with round to convoluted nuclei, coarse to clumped chromatin, rare prominent nucleoli, and moderate amounts of lightly basophilic cytoplasm that frequently contained small magenta granules and/or clear vacuoles. The animal had tested negative for several viruses and other etiologic agents found in nonhuman primates 1 week prior to shipment to the research facility. However, further evaluation of the blood smear revealed rare hemoflagellates, and later testing using real-time PCR and ELISA was confirmatory for Trypanosoma cruzi (T cruzi). Trypanosoma cruzi is a zoonotic pathogen responsible for Chagas disease in people and can have negative consequences on study results when positive animals are inadvertently used for preclinical research. This case report describes a marked large granular lymphocytosis in an otherwise healthy macaque as the only indication of infection with T cruzi in an animal believed to be negative for the infection. Additionally, it highlights the diagnostic limitations of screening tests to rule out diseases in animals intended to be used in preclinical studies.     

Effects of trilostane on the pituitary-adrenocortical and renin–aldosterone axis in dogs with pituitary-dependent hypercortisolism

The medical records of 63 dogs with pituitary-dependent hypercortisolism (PDH) before and during treatment with trilostane were reviewed retrospectively. The correct trilostane dosage in dogs with PDH was based on the resolution of clinical signs and the results of an adrenocorticotropic hormone (ACTH) stimulation test. The mean (±SD) dose rate of trilostane to achieve good clinical control was 2.8 ± 1.0 mg/kg bodyweight. Trilostane treatment resulted in a significant decline in basal plasma cortisol concentrations. The median plasma ACTH concentration (39 pmol/L, range 7–132 pmol/L; n = 60) at the optimal trilostane dosage time was significantly higher (P < 0.001) than before treatment (13 pmol/L, range 2–102 pmol/L). These values did not overlap with plasma ACTH concentrations (range 212–307 pmol/L) of five PDH dogs with trilostane-induced hypocortisolism.The median cortisol/ACTH ratio in well-controlled dogs (0.23, range 0.03–2.5; n = 46) was significantly lower (P < 0.001) than before treatment (2.59, range 0.27–13.25). Trilostane treatment resulted in an insignificant decrease in plasma aldosterone concentration (PAC), but the median plasma renin activity (PRA) at the time the trilostane dosage was considered optimal (265 fmol/L/s, range 70–3280 fmol/L/s; n = 18) was significantly higher (P < 0.001) than prior to treatment (115 fmol/L/s, range 15–1330 fmol/L/s). Similarly, the median PAC/PRA ratio during trilostane treatment (0.16, range 0.003–0.92; n = 17) was significantly lower (P < 0.001) than before treatment (median 0.44, range 0.04–1.33). Trilostane affected both the hypothalamic-pituitary-adrenocortical and the renin–aldosterone axes. The results also suggested that basal plasma ACTH concentration may be used to detect trilostane overdosage.     

Potency and effect ofBacillus thuringiensis preparations against larvae ofSpodoptera littoralis andBoarmia (Ascotis) selenaria

The potency of two newBacillus thuringiensis (B.t.) preparations (coded ABG 6104 and ABG 6105) and of Dipel (B. thuringiensis var.kurstaki) was determined againstSpodoptera littoralis (Boisd.) 5th-instar larvae on a calcium-alginate diet. With this bioassay, the newB.t. products were more than twice as potent as Dipel. They were also 2–3 times more active than Dipel on alfalfa and cotton leaves in the laboratory. When applied in an alfalfa field at the rate of 312 mg/m², ABG 6104 and ABG 6105 caused 40% mortality of 5th-instar larvae and reduced the weight of the survivors to 30–40% of the control; only half of this activity was obtained with Dipel. On cotton, the activity of all theB. t. products was low. NeonateS. littoralis larvae were effectively controlled on avocado seedlings; however, there was high mortality also in the untreated controls. All threeB. t. preparations had a similar effect onBoarmia (Ascotis) selenaria Schiff. on avocado leaves in the laboratory. Addition of a chitinase enzyme did not increase the pathogenicity of the microbial preparations in the latter tests.     

Characterization of Pectobacterium brasiliense strains from potato and vegetables in Israel

Pectobacterium brasiliense (Pbr) infects a wide range of crops worldwide, causing potato blackleg and soft rot and vegetable soft rots. This study aimed to characterize the genetic diversity and virulence variability among 68 Pbr strains isolated from either symptomless potato progeny tubers, diseased potato plants, ware potatoes wash water, or vegetables grown in Israel, as well as strains isolated from symptomless seed tubers grown in Europe, or diseased potato plants grown in France. The collection was typed using PCR and TaqMan real-time PCR analyses, dnaX sequence analysis, pulsed-field gel electrophoresis (PFGE), and pectolytic activity. dnaX phylogeny grouped almost all strains in a common genetic clade related to Pbr, which was distinct from the other Pectobacterium species. PFGE analysis identified two main clusters, including one major group of 47 strains with 95%–100% similarity. Maceration assays on two potato cultivars showed significant differences between strains but with no correlations with the source of the strains nor the status of the host (with/without symptoms). Molecular (dnaX sequences and PFGE profiles) and phenotypic analyses (tuber maceration tests) showed that the tested Pbr strains are not a homogeneous group. Analysis of the tested Pbr strains isolated from potato and vegetables grown in fields with a history of potato cultivation suggests that seed tubers imported from Europe may be the main source for Pbr in Israel. To the best of our knowledge, this is the first study that describes biodiversity and population structure of P. brasiliense isolated from potato and vegetables under hot climate conditions.     

Isoflavone levels in five soybean (Glycine max) genotypes are altered by phytochrome-mediated light treatments

The objective of the present study was to determine whether concentrations of different isoflavones (puerarin, genistein, genistin, daidzein, and daidzin) in shoots and roots of five selected soybean genotypes would respond the same or differently to red (650 nm peak transmittance) and far-red (750 nm peak transmittance) light treatments given under controlled environments. Levels of isoflavones (mg g(-1) dry weight biomass) present in seeds, control roots, and shoots and 10 day light-treated seedlings (light, dark, red, and far-red wavelengths) of soybean (Glycine max) were determined by high-performance liquid chromatography analysis in comparison with known isoflavone standards. Seeds of the five soybean genotypes studied consistently stored most of their isoflavones as glucosyl conjugates (e.g., daidzin, genistin, and puerarin). For the five soybean genotypes, isoflavone levels were lower in the seeds as compared with roots plus shoots of control, time zero (first true leaf stage) seedlings. Following 10 days of the respective light treatments, we found that (i) isoflavone levels were enhanced in dark-grown plants over light-grown plants for three of the five genotypes (a new finding) and the reverse occurred for a single genotype (a typical response of legumes) and (ii) generally, far-red end of day (EOD) light treatment enhanced total isoflavone levels in roots plus shoots over red EOD light treatment. Results from the present study show that phytochrome does appear to play a role in regulating isoflavone levels in developing soybean seedlings and that this influence by red/far-red-mediated phytochrome reactions is strongly dependent on the genotypes selected for study.