Dinoseb toxicosis in two dogs

Two male English Setters were noticed to be breathing rapidly, hyperexcitable, and atactic after roaming a rural area for 2 hours. Both dogs' cost were stained with yellow liquid. One dog died while en route to the veterinarian. Treatment was begun for the surviving dog for what was initially diagnosed to be organophosphorus or carbamate insecticide toxicosis. Before the diagnosis could be confirmed, the second dog died. The yellow liquid on the dogs' skin was identified as dinoseb in high concentrations. Dinoseb is an acutely toxic, substituted dinitrophenolic herbicide believed to act as an uncoupler of electron transport from oxidative phosphorylation.     

Detection of molecular alignment in confined films

Optical second harmonic generation was used to study the in-plane alignment of self-assembled silane monolayers attached to a glass surface under mechanical loading. The measurements allow correlation of the macroscopic forces acting on the monolayer with the average orientation and the azimuthal molecular alignment of the terminal molecular entity. Compression and shear forces lead to an alignment of the initially randomly oriented molecules on a macroscopic length scale. The change in azimuthal alignment of molecules under mechanical stress was found to be irreversible on the time scale of 12 hours, whereas changes of the molecular tilt angle were reversible.     

Myocardial and pancreatic lesions induced by T-2 toxin, a trichothecene mycotoxin, in swine

Myocardial and pancreatic lesions induced by sublethal doses of T-2 toxin in swine were characterized by light and electron microscopy. Toxin was given intravenously to six 17- to 18-week-old pigs. Pigs were killed 24 or 48 hours after treatment. Grossly, subendocardial hemorrhages, multifocal pinpoint white foci in myocardium, and pancreatic edema occurred in one treated pig. Histologic changes in myocardium of treated pigs consisted of multifocal edema, mononuclear cell infiltration, myofiber hyalinization, vacuolation, and contraction bands with nuclear pyknosis. Ultrastructurally, there were areas of edema, myofibrillar disorganization, dilation of sarcoplasmic reticulum, and formation of hypercontraction bands. Myocardial mineralization was seen in the pig with gross lesions. Pancreatic changes in treated pigs consisted of multifocal acinar degeneration and necrosis. Ultrastructural changes included irregular dilation of rough endoplasmic reticulum and abnormal zymogen granules. Thus, in addition to radiomimetic lesions of the gastrointestinal tract and lymphoid organs, heart and pancreas are target organs of T-2 toxin in swine.     

Comparative analysis of MAPK and PI3K/AKT pathway activation and inhibition in human and canine melanoma

The lack of advanced animal models of human cancers is considered a barrier to developing effective therapeutics. Canine and human melanomas are histologically disparate but show similar disease progression and response to therapies. The purpose of these studies was to compare human and canine melanoma tumours and cell lines regarding MAPK and PI3K/AKT signalling dysregulation, and response to select molecularly targeted agents. Pathway activation was investigated via microarray and mutational analysis. Growth inhibition and cell cycle effects were assessed for pathway inhibitors AZD6244 (MAPK) and rapamycin (PI3K/AKT) in human and canine melanoma cells. Human and canine melanoma share similar differential gene expression patterns within the MAPK and PI3K/AKT pathways. Constitutive pathway activation and similar sensitivity to AZD6244 and rapamycin was observed in human and canine cells. These results show that human and canine melanoma share activation and sensitivity to inhibition of cancer‐related signalling pathways despite differences in activating mutations.     

Pharmacokinetics of norfloxacin in dogs after single intravenous and single and multiple oral administrations of the drug

Norfloxacin was given to 6 healthy dogs at a dosage of 5 mg/kg of body weight IV and orally in a complete crossover study, and orally at dosages of 5, 10, and 20 mg/kg to 6 healthy dogs in a 3-way crossover study. For 24 hours, serum concentration was monitored serially after each administration. Another 6 dogs were given 5 mg of norfloxacin/kg orally every 12 hours for 14 days, and serum concentration was determined serially for 12 hours after the first and last administration of the drug. Complete blood count and serum biochemical analysis were performed before and after 14 days of oral norfloxacin administration, and clinical signs of drug toxicosis were monitored twice daily during norfloxacin administration. Urine concentration of norfloxacin was determined periodically during serum acquisition periods. Norfloxacin concentration was determined, using high-performance liquid chromatography with a limit of detection of 25 ng of norfloxacin/ml of serum or urine. Serum norfloxacin pharmacokinetic values after single IV dosing in dogs were best modeled, using a 2-compartment open model, with distribution and elimination half-lives of 0.467 and 3.56 hours (harmonic means), respectively. Area-derived volume of distribution (Vd area) was 1.77 +/- 0.69 L/kg (arithmetic mean +/- SD), and serum clearance (Cls) was 0.332 +/- 0.115 L/h/kg. Mean residence time was 4.32 +/- 0.98 hour. Comparison of the area under the curve (AUC; derived, using model-independent calculations) after iv administration (5 mg/kg) with AUC after oral administration (5 mg/kg) in the same dogs indicated bioavailability of 35.0 +/- 46.1%, with a mean residence time after oral administration of 5.71 +/-2.24 hours. Urine concentration was 33.8 +/- 15.3 micrograms/ml at 4 hours after a single dose of 5 mg/kg given orally, whereas concentration after 20 mg/kg was given orally was 56.8 +/- 18.0 micrograms/ml at 6 hours after dosing. Twelve hours after drug administration, urine concentration was 47.4 +/- 20.6 micrograms/ml after the 5-mg/kg dose and 80.6 +/- 37.7 micrograms/ml after the 20/mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inconspicuous Nutrient Laden Surface Runoff from Mature Forest Sierran Watersheds

It is generally held that surface runoff in heavily forested ecosystems is minimal and therefore nutrient fluxes via runoff are unimportant. This is based in large measure on the absence of direct observation or remnant physical evidence. It is further held that protected forests with heavy understory and litter serve as a nutrient sink due to maximum uptake and interception. Our Sierran studies have detected the presence of surface runoff at several sites in the form of both overland and litter interflow with concentrations of NH₄-N as high as 87.2 mg L^?1, NO₃-N as high as 95.4 mg L^?1, and PO₄-P as high as 24.4 mg L^?1. Data suggest that nutrients are derived from the mature O-horizons, and that there has been little contact with the mineral soil or root zone where strong retention and/or uptake of these ions would be expected. Such contributions from overland/interflow could be particularly important in areas where ultra-oligotrophic lakes (e.g., Lake Tahoe) are now trending towards meso-oligotrophic status. We believe that fire exclusion in these systems may have exacerbated N and P inputs to Lake Tahoe and elsewhere by allowing unnatural buildups of O-horizons that are apparently a source of nutrients to surface runoff.     

Pliocene paleoclimate and East antarctic ice-sheet history from surficial ash deposits

The preservation, age, and stratigraphic relation of an in situ ashfall layer with an underlying desert pavement in Arena Valley, southern Victoria Land, indicate that a cold-desert climate has persisted in Arena Valley during the past 4.3 million years. These data indicate that the present East Antarctic Ice Sheet has endured for this time and that average temperatures during the Pliocene in Arena Valley were no greater than 3 degrees C above present values. One implication is that the collapse of the East Antarctic Ice Sheet due to greenhouse warming is unlikely, even if global atmospheric temperatures rise to levels last experienced during mid-Pliocene times.     

Solid ion-exchange electrode selective for calcium ion

A calcium-selective electrode with solid ion exchanger was prepared from a solution of the calcium salt of a dialkylphosphoric acid in collodion. The electrode responds rapidly and reproducibly to activity of calcium ion and demonstrates a selective response for calcium ion in the presence of alkaline earth and alkali metal cations.