Advances in the application of neuropeptides in insect control

The development of a new approach for the generation of a novel type of putative insect control agents based on backbone cyclic peptidomimetic antagonists of insect-neuropeptides is reported. The approach, termed the backbone cyclic neuropetide based on autogonist (BBC-NBA) was applied to the insect pyrokinin/pheromone biosynthesis activating neuropeptide (PBAN) family as a model, and led to the discovery of a potent linear lead antagonist and several highly potent, metabolically stable BBC peptidomimetic antagonists, devoid of agonistic activity, which inhibited in vivo PBAN-mediated activities in moths.     

Phase I trial and pharmacokinetic analysis of ifosfamide in cats with sarcomas

OBJECTIVE: To determine the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of ifosfamide in tumor-bearing cats. ANIMALS: 38 cats with resected, recurrent, or metastatic sarcomas. PROCEDURE: The starting dosage of ifosfamide was 400 mg/m(2) of body surface area, IV, and dosages were increased by 50 to 100 mg/m(2) in cohorts of 3 cats. To protect against urotoxicosis, mesna was administered at a dosage equal to 20% of the calculated ifosfamide dosage. Diuresis with saline (0.9% NaCl) solution before and after administration of ifosfamide was used to minimize nephrotoxicosis. Samples for pharmacokinetic analysis were obtained after the MTD was reached. RESULTS: 38 cats were entered into this phase I study and were administered a single dose of ifosfamide at various dosages. The MTD was 1,000 mg/m(2), and neutropenia was the DLT. Seven of 8 episodes of neutropenia were on day 7 after treatment, and 1 cat developed severe neutropenia on day 5. Adverse effects on the gastrointestinal tract were generally mild and self-limiting, the most common of which was nausea during ifosfamide infusion. One cat had signs consistent with a drug-induced hypersensitivity reaction. There were no episodes of hemorrhagic cystitis or nephrotoxicosis. Correlations between pharmacokinetic variables and ifosfamide-associated toxicoses were not found. Preliminary evidence of antitumor activity was observed in 6 of 27 cats with measurable tumors. CONCLUSIONS AND CLINICAL RELEVANCE: The dosage of ifosfamide recommended to treat tumor-bearing cats is 900 mg/m(2) every 3 weeks. This dosage should be used in phase II clinical trials.     

Lomustine for treatment of mast cell tumors in cats: 38 cases (1999-2005)

OBJECTIVE: To determine clinical activity and toxic effects of lomustine when used to treat cats with mast cell tumors (MCTs). DESIGN: Retrospective case series. ANIMALS: 38 cats with measurable, histologically or cytologically confirmed MCTs treated with lomustine at a dosage > or = 50 mg/m(2). PROCEDURES: Medical records were reviewed to determine response to treatment and evidence of drug toxicoses. The Kaplan-Meier method was used to estimate remission duration. RESULTS: 26 cats had cutaneous MCTs, 7 had MCTs of the mesenteric lymph nodes, 2 had gastrointestinal tract MCTs, 2 had hepatic MCTs, and 1 had MCTs involving multiple organs. Targeted lomustine dosage was 50 mg/m(2) in 22 cats and 60 mg/m(2) in 16 cats. Median administered dosage of lomustine was 56 mg/m(2) (range, 48 to 65 mg/m(2)), and median number of doses administered was 2 (range, 1 to 12). Seven cats had a complete response and 12 had a partial response, for an overall response rate of 50%. Median response duration was 168 days (range, 25 to 727 days). The most common toxicoses were neutropenia and thrombocytopenia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that lomustine had activity against MCTs in cats and was well tolerated. Further, findings suggested that treatment with lomustine should be considered for cats with MCTs for which local treatment is not an option.     

Screening for phyto‐toxic contaminants in an industrial source of nutrients intended for foliar and root fertilization

Plant screening assays were used to determine whether significant levels of growth inhibitory and phytotoxic contaminants were present in a new industrial source of potassium dihydrogen phosphate fertilizer intended for foliar and root application. Maize (Zea mays L.) plants hydroponically cultured in a controlled environment chamber, were used for the assays. The threshold concentration of industrial potassium phosphate which just caused burn damage symptoms, when applied as standard droplets to the leaf surface with Tween 80 wetting agent was 0.5M. The comparative threshold concentration for damage by an ultrapure analytical grade of potassium phosphate was >0.6M. Thus, the industrial grade had slightly higher toxicity for leaf application. Effects on plants of supplying industrial and analytical grade phosphates via the roots were also compared. Root and leaf elongation kinetics, mature leaf cell lengths, apparent capacity for leaf cell production, shoot ontogeny, and shoot fresh weight yields were determined at low and high potassium phosphate concentrations. The effects of analytical and industrial grade fertilizer salts were equivalent. We suggest that these rapid and relatively simple plant screening assays can provide a useful safety check, prior to large scale field trails, for fertilizer nutrients produced by new industrial processes.     

Streptozocin for treatment of pancreatic islet cell tumors in dogs: 17 cases (1989-1999)

OBJECTIVE: To determine toxic effects of streptozocin given in combination with a diuresis protocol in dogs and establish whether streptozocin is efficacious in treatment of pancreatic islet cell tumors in dogs. DESIGN: Retrospective study. ANIMALS: 17 dogs. PROCEDURE: Medical records were reviewed to obtain information regarding signalment, tumor stage and staging tests performed, number of streptozocin treatments, adverse effects, results of biochemical and hematologic monitoring during streptozocin treatment, tumor dimensions, duration of normoglycemia, and date of death, when applicable. Dogs were compared with a historical control group of 15 dogs treated surgically and medically. RESULTS: 58 treatments were administered to the 17 dogs. Only 1 dog developed azotemia. Serum alanine aminotransferase activity increased in some dogs but decreased when treatment was discontinued. Hematologic toxicoses were rare. Vomiting during administration was uncommon but occasionally severe. Two dogs developed diabetes mellitus after receiving 5 doses. Median duration of normoglycemia for 14 dogs with stage-II or -III insulinoma treated with streptozocin was 163 days (95% confidence interval, 16 to 309 days), which was not significantly different from that for the control dogs (90 days; 95% confidence interval, 0 to 426 days). Two dogs had rapid resolution of paraneoplastic peripheral neuropathy, and 2 others had measurable reductions in tumor size. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that streptozocin can be administered safely to dogs at a dosage of 500 mg/m2, IV, every 3 weeks when combined with a protocol for induction of diuresis and may be efficacious in the treatment of dogs with metastatic pancreatic islet cell tumors.     

Seasonal abundance of the western flower thripsFrankliniella occidentalis in the arava valley of Israel

Flowers of 22 plant species grown in the Arava region of Israel were sampled at periodic intervals to study the seasonal abundance ofFrankliniella occidentalis (Pergande) (Thysanoptera: Thripidae). Samples were collected from the most common cut-flower and vegetable plant species in this area during 1997 and from pepper in 1996–1998. Western flower thrips (WFT) was detected on 19 of the plant species surveyed, and it reproduced on numerous plant species. WFT counts peaked in late February–April and in October–December. The peak density of WFT during March in our survey corresponded to the peak flowering of cut-flower plants (during spring) and sweet pepper (during autumn). Thrips population was less abundant during autumn than in spring and was very low during summer. The possible reasons for fluctuations in thrips densities are abiotic factors (temperature and relative humidity), and availability of flowering plants. The high temperature (>40°C) and low humidity (∼20%) in summer caused a drastic reduction in WFT populations, although some flowering plant species were available in this season. WFT population remained low until October, when adults appeared in large numbers on flowering pepper. We assume that the thrips had survived the hottest months by aestivation and migrated to the plants when air temperature decreased. In most samples from the cut-flower fields, 84.8% were adult WFT; only during the period from the end of January to March, did the proportion of immature stages in the thrips population increase to 31.6%. Females always outnumbered males (71% females). In pepper fields during the first cropping month the thrips population included 96% adults; from November onwards, the proportions of adults and immatures were almost equal; and females outnumbered males. Organic pepper fields were not infested with thrips because of the presence of the predatory bugOrius albidipennis (Fieber). Contribution from the Agricultural Research Organization. No. 534/00, 2000 series. http://www.phytoparasitica.org posting July 16, 2002.     

The conversion of a RFLP assay into PCR for the determination of purity in a hybrid pepper cultivar

Summary A RFLP assay which had been developed for distinguishing between a hybrid pepper and its parents, has been converted into a simple applicable PCR assay, suitable for large-scale quality-control assessment of the commercial hybrid. For this conversion the sequences of the ends of the probe used in the previous RFLP assay were determined. From these sequences suitable primers were devised for inverse PCR of heterogeneous DNA fragments derived from the male parent. The inverse-PCR product was cloned and partially sequenced. These sequences, in turn, made it possible to determine primers on both sides of the locus of mutation, and to develop the reported conventional PCR assay.     

Clinical characteristics, treatment, and outcome of dogs with presumed primary hepatic lymphoma: 18 cases (1992-2008)

OBJECTIVE-To determine outcome of dogs with presumed primary hepatic lymphoma treated with various multiagent, doxorubicin-based chemotherapeutic protocols and identify factors associated with prognosis. DESIGN-Retrospective case series. ANIMALS-18 dogs with presumed primary hepatic lymphoma. PROCEDURES-Medical records were reviewed for information on signalment, treatment, and outcome. RESULTS-8 dogs had a complete remission (CR), with a median remission duration of 120 days. Dogs with leukocytosis, neutrophilia, hypoalbuminemia, hyperbilirubinemia, or a combination of hypoalbuminemia and hyperbilirubinemia were less likely to achieve a CR. Overall median survival time (MST) was 63 days (range, 2 to 402 days). In a multivariate analysis, response to treatment and serum albumin concentration were associated with MST. Dogs that did not achieve a CR had a significantly shorter MST than did dogs that did achieve a CR (13 vs 283 days, respectively). Dogs with serum albumin concentration < 2.5 g/dL at the time treatment was initiated had a significantly shorter MST than did dogs with serum albumin concentration within reference limits (10 vs 128 days, respectively). There was also a positive correlation between serum albumin concentration and survival time (r = 0.74). CONCLUSIONS AND CLINICAL RELEVANCE-Results suggested that dogs with primary hepatic lymphoma that underwent chemotherapy had a poor prognosis, with a low response rate. Dogs that responded to treatment had a better prognosis, and dogs with hypoalbuminemia had a poorer prognosis.     

Evaluation of factors associated with survival in dogs with untreated nasal carcinomas: 139 cases (1993-2003)

OBJECTIVE: To evaluate factors associated with survival in dogs with nasal carcinomas that did not receive treatment or received only palliative treatment. DESIGN: Retrospective case series. ANIMALS: 139 dogs with histologically confirmed nasal carcinomas. PROCEDURES: Medical records, computed tomography images, and biopsy specimens of nasal carcinomas were reviewed. Only dogs that were not treated with radiation, surgery, chemotherapy, or immunotherapy and that survived > or = 7 days from the date of diagnosis were included. The Kaplan-Meier method was used to estimate survival time. Factors potentially associated with survival were compared by use of log-rank and Wilcoxon rank sum tests. Multivariable survival analysis was performed by use of the Cox proportional hazards regression model. RESULTS: Overall median survival time was 95 days (95% confidence interval [CI], 73 to 113 days; range, 7 to 1,114 days). In dogs with epistaxis, the hazard of dying was 2.3 times that of dogs that did not have epistaxis. Median survival time of 107 dogs with epistaxis was 88 days (95% CI, 65 to 106 days) and that of 32 dogs without epistaxis was 224 days (95% CI, 54 to 467 days). CONCLUSIONS AND CLINICAL RELEVANCE: The prognosis of dogs with untreated nasal carcinomas is poor. Treatment strategies to improve outcome should be pursued.