Checking that replication breakdown is not terminal

Two new studies help to clarify the relationship between checkpoint proteins, recombination, and replication fork integrity.     

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.     

Feline Lymphoma (145 Cases): Proliferation Indices, Cluster of Differentiation 3 Immunoreactivity, and Their Association with Prognosis in 90 Cats

Paraffin-embedded, formalin-fixed tissue samples from 145 cats with lymphoma were analyzed for cluster of differentiation 3 (CD3, a surface antigen) immunoreactivity, argyrophilic nucleolar organizer region (AgNOR) frequency, and proliferating cell nuclear antigen labeling index (PCNA-LI). This information along with signalment, anatomic site, and feline leukemia virus (FeLV) antigen status was used to determine the potential of these indicators to predict response to therapy, remission, and survival times, and to characterize cats with lymphoma in the era of general availability of FeLV testing and vaccination. Alimentary lymphoma, primarily occurring in older, FeLV-negative cats, was the most common site of involvement. Although the majority of tumors from FeLV-positive cats were CD3-immunoreactive, only one half of CD3-immunoreactive tumors occurred in FeLV-positive cats. Median remission duration and survival times were 126 days and 143 days, respectively, for all cats. Measures of tumor cell proliferation (AgNOR frequency and PCNA-LI) and CD3-immunoreactivity were not predictive of outcome. When all prognostic factors were accounted for by multivariate analysis, response to therapy, FeLV status, and clinical substage were predictive of outcome. FeLV-negative cats that achieved a complete response following induction therapy were likely to have durable (ie, > 6-month) responses, particularly when doxorubicin was included in the chemotherapy protocol. However, FeLV-positive cats had significantly shorter remission and survival times with available chemotherapeutic protocols.     

Verbena × hybrida flower volatiles attractive to Western flower thrips,Frankliniella occidentalis

Western flower thrips (WFT) are attracted to three flowering verbena cultivars. The volatile components of these cultivars contain different enantiomers of linalool oxide which have been synthesised and one shown to be attractive to WFT.     

Optimum selenium levels in diets high in plant‐based feedstuffs for gilthead sea bream (Sparus aurata) fingerlings

Substitution of marine ingredients (FM‐FO) by plant protein and oil sources can modify selenium (Se) levels in feeds. Se plays an important role in the antioxidative defence by forming part of selenoproteins. Se requirements of gilthead sea bream are not accurately determined; therefore, this study was conducted to define Se supplementation levels in low FM‐FO practical diets for sea bream fingerlings. A plant‐based diet containing 0.45 mg Se/kg diet was used as the basal diet. Four other diets were supplemented to contain 0.68, 0.86, 1.00 or 1.70 mg Se/kg diet, supplied as sodium selenite. Sea bream, weighing 12.6 ± 1.4 g, were distributed in triplicate groups per diet and fed for 42 days. Se supplementation up to 1.00 mg Se/kg significantly improved the growth of sea bream, whereas further increase up to 1.70 mg Se/kg diet reduced growth. The results of this study suggest that the optimum dietary levels of sodium selenite in diets with low FM‐FO with basal levels of 0.45 mg Se/kg are around 0.94 mg Se/kg to promote growth of gilthead sea bream juveniles. On the contrary, dietary levels of 1.70 mg Se/kg were found to be excessive and caused growth reduction, increased catalase expression and hydropic degeneration in the liver.     

Dietary micronutrient composition affects fillet texture and muscle cell size in Atlantic salmon (Salmo salar)

During the past 20 years, plant ingredients have taken over as the main constituents in feed for Atlantic salmon. This has changed the nutrient composition of the feeds, the bioavailability of nutrients and perhaps nutrient metabolism. Plant‐based diets also contain more anti‐nutrients. The EU‐funded project ARRAINA re‐evaluated recommendations for micronutrient supplementation to Atlantic salmon feeds, and the present study compared a diet supplemented with micronutrients according to NRC (2011) (control diet, 100% NP (nutrient package)) with a diet supplemented according to the new recommendations (New NP). Tissue concentrations of pyridoxine, pantothenic acid, niacin, vitamin C, Zn and Se were significantly higher; and Cu was lower in Atlantic salmon fed the diet with the New NP compared to the control fish. The New NP also gave a near significant effect on growth, decreased muscle firmness and increased muscle cell size, and it affected metabolism of nitrogen‐containing metabolites in the muscle. While we cannot be certain which micronutrient(s) gave these effects, the B vitamins are probable candidates, since they are mediators of intermediary metabolism and have been shown to influence some of the affected metabolites.     

Proinsecticides effective against insecticide-resistant peach-potato aphid (Myzus persicae (Sulzer))

A range of potential proinsecticides was synthesised and tested against insecticide-susceptible and -resistant clones of Myzus persicae (Sulzer). They were all esters of compounds known to be toxic or pharmacologically active, and were designed to have increased lipophilicity and to be subject to more rapid activation by hydrolysis in resistant than in susceptible aphids due to the increased amount of esterase present in the resistant clones. The most potent toxins were esters of monofluoroacetic acid. When applied topically, the toxicity of these esters to M. persicae was directly proportional to the esterase content of the aphids. Such compounds would not be suitable as commercial insecticides, but the results serve to illustrate the potential benefits of exploiting a resistance mechanism against one class of compounds to render another class more toxic, i.e. to design compounds that show negative cross-resistance. © 1998 SCI     

The isolation and possible significance of some toxic mammalian metabolites of diazinon

The recognition and isolation of toxic metabolites of diazinon by gas, thin-layer, column and high-pressure liquid chromatography is discussed. The possible toxicological significance of these compounds is considered and some preliminary attempts to assess their importance by experiments with microsomal preparations are mentioned.     

Esterase-inhibiting photo-oxidation products from the organophosphorus insecticide pyrimithate

Pyrimithate (2-dimethylamino-6-methylpyrimidin-4-yl diethyl phosphorothio-nate) decomposes when exposed to u.v. light in the presence of air to a complex mixture of products, some of which inhibit esterases directly or indirectly. Separation of the mixture by thin-layer and liquid chromatography gave five pure components in sufficient quantity for spectroscopic identification. A sixth was tentatively identified. The structures ( II-VII ) show that oxidative attack occurs at the dimethylamino group and at the sulphur atom.     

Metabolic aspects of the toxicology of diazinon. I. Hepatic metabolism in the sheep,cow, pig,guinea-pig,rat, turkey,chicken and duck

The phosphorothionate insecticide diazinon was incubated with liver microsomes from the sheep, cow, pig, guinea-pig, rat, turkey, chicken and duck. Metabolism by liver slices of most of these species was also examined. Hydroxydiazinon, isohydroxydiazinon, dehydrodiazinon, their oxons and diazoxon were identified and determined quantitatively or semi-quantitatively. An eighth metabolite was tentatively identified as the 6-aldehyde analogue of diazinon. Yields and rates of production of these metabolites varied greatly between species. Production of oxons was not generally correlated with susceptibility to diazinon poisoning, although it was lowest in the least susceptible animal, the sheep. The degradation of oxons by liver slices was too slow to explain the low toxicity of diazinon to the mammals. The relative importance of hepatic and extrahepatic metabolism in determining toxicity to vertebrates is discussed.