The pharmacokinetics of intravenous fenoldopam in healthy,awake cats

Fenoldopam is a selective dopamine‐1 receptor agonist that improves diuresis by increasing renal blood flow and perfusion and causing peripheral vasodilation. Fenoldopam has been shown to induce diuresis and be well‐tolerated in healthy cats. It is used clinically in cats with oliguric kidney injury at doses extrapolated from human medicine and canine studies. The pharmacokinetics in healthy beagle dogs has been reported; however, pharmacokinetic data in cats are lacking. The goal of this study was to determine pharmacokinetic data for healthy, awake cats receiving an infusion of fenoldopam. Six healthy, awake, client‐owned cats aged 2–6 years old received a 120‐min constant rate infusion of fenoldopam at 0.8 μg/kg/min followed by a 20‐min washout period. Ascorbate stabilized plasma samples were collected during and after the infusion for the measurement of fenoldopam concentration by HPLC with mass spectrometry detection. This study showed that the geometric mean of the volume of distribution, clearance, and half‐life (198 mL/kg, 46 mL/kg/min, and 3.0 mins) is similar to pharmacokinetic parameters for humans. No adverse events were noted. Fenoldopam at a constant rate infusion of 0.8 μg/kg per min was well tolerated in healthy cats. Based on the results, further evaluation of fenoldopam in cats with kidney disease is recommended.     

The efficacy of benzimidazole anthelmintics against late fourth stage larvae of Trichostrongylus colubriformis in gerbils and Nippostrongylus brasiliensis in rats

The efficacy of eight benzimidazole anthelmintics has been examined against Trichostrongylus colubriformis in gerbils and Nippostrongylus brasiliensis in rats, when the parasites were entering into the fourth and final moult. The dose--response slopes obtained from the data for both host--parasite systems did not deviate significantly from a non-parallel model, and were used for relative potency determinations. The T. colubriformis assay ranked the benzimidazoles in order of potency as follows: albendazole, oxfendazole, fenbendazole, cambendazole, mebendazole, oxibendazole, parbendazole and thiabendazole. This compares favourably with the expected relative efficacies against trichostrongyles in sheep. N. brasiliensis was found to be far less useful in this respect. All compounds tested, with the exception of thiabendazole, were highly effective against both parasites. The T. colubriformis/gerbil assay could be a very useful tool for preliminary in vivo evaluation and possibly in the early selective optimisation of chemical series.     

Cryopreservation of Ram Semen in Extenders Containing Soybean Lecithin as Cryoprotectant and Hyaluronic Acid as Antioxidant

A soybean lecithin‐based extender supplemented with hyaluronic acid (HA) was assayed for effectiveness to improve the quality of frozen–thawed ram semen. HA has not been tested yet in an extender containing soybean lecithin for freezing ram semen. Thus, the aim of this study was to analyse the effects of soybean lecithin at 1% or 1.5% along with HA at 0, 0.5 and 1 mg ml^‐1 in a Tris‐based extender on the motion characteristics, membrane integrity (HOST), viability, GSH peroxidase (GSH‐PX) activity, lipid peroxidation and acrosomal status after freezing–thawing. Semen was collected from four Mehraban rams during the breeding season and frozen in the six lecithin×HA extenders. The extender containing 1.5% lecithin supplemented with no HA yielded higher total motility (52.5%±1.6), viability (55.8%±1.6) and membrane integrity (44.5%±1.7), but the effects of the lecithin concentration did not reach signification. Linearity‐related parameters, ALH, BCF, lipid peroxidation, GSH‐PX activity, morphology and acrosomal status were not affected by the extender composition. In general, adding HA significantly decreased sperm velocity (1 mg ml^‐1 HA), total motility (only with 1.5% lecithin), viability (1 mg ml^‐1 HA for 1% lecithin; both concentrations for 1.5% lecithin) and membrane integrity. In conclusion, adding HA to the freezing extender supplemented with soybean lecithin failed to improve quality‐related variables in ram semen. Increasing the lecithin content could have a positive effect, but further studies are needed.     

Determination of Feeder Cell‐Based Cellular Niches Supporting the Colonization and Maintenance of Spermatogonial Stem Cells from Prepubertal Domestic Cat Testes

Recently, isolation and in vitro culture of putative spermatogonial stem cells (SSCs) in the domestic cat have been conducted. However, the cellular niche conditions that facilitate the establishment and long‐term maintenance of feline SSCs (FSSCs) have not been described. Therefore, we investigated the type of feeder cells used to stimulate colony formation and growth of FSSCs among the various factors in the FSSC niche. Spermatogonial stem cells isolated from feline testes were cultured on mitotically inactivated testicular stromal cells (TSCs) derived from cats, dogs and mice, and mouse embryonic fibroblasts (MEFs). The formation and growth of colonies derived from SSCs cultured on each type of feeder cell were identified at passage 0, and the morphology, alkaline phosphatase (AP) activity and expression of SSC‐specific genes in surviving colonies were investigated at passage 4. Among these diverse feeder cells, TSCs from cat showed the greatest colony formation, growth and maintenance of FSSCs, and SSC colonies cultured by passage 4 showed a typical dome‐shaped morphology, AP activity and expression of SSC‐specific genes (NANOG, OCT4, SOX2 and CD9). Accordingly, these results demonstrate that feline TSCs could be used as feeder cells to support the establishment and maintenance of SSCs from domestic cats.     

Superradiance in a torus magnetosphere around a black hole

The coalescence of a neutron star and a black hole in a binary system is believed to form a torus around a Kerr black hole. A similarly shaped magnetosphere then results from the remnant magnetic field of the neutron star. In the strong-field case, it contains a cavity for plasma waves located between the barrier of the gravitational potential and the surrounding torus. This cavity may be unstable to superradiance of electromagnetic waves. Superradiant amplification of such waves, initially excited by turbulence in the torus, should inflate into a bubble in a time as short as approximately 0.75 (1 percent/&cjs3539;epsilon&cjs3539;2)(M/7M middle dot in circle) seconds approximately 0.15 to 1.5 seconds, assuming an efficiency &cjs3539;epsilon&cjs3539;2 = 0.5 to 5 percent and a mass M = 7M middle dot in circle. These bubbles may burst and repeat, of possible relevance to intermittency in cosmological gamma-ray bursts. The model predicts gamma-ray bursts to be anticorrelated with their gravitational wave emissions.     

Effect of dietary soy on serum thyroid hormone concentrations in healthy adult cats

OBJECTIVE: To compare effects of short-term administration of a soy diet with those of a soy-free diet on serum thyroid hormone concentrations in healthy adult cats. ANIMALS: 18 healthy adult cats. PROCEDURE: Cats were randomly assigned to receive either a soy or soy-free diet for 3 months each in a crossover design. Assays included CBC, serum biochemical profile, thyroid hormone analysis, and measurement of urinary isoflavone concentrations. RESULTS: Genistein, a major soy isoflavone, was identified in the urine of 10 of 18 cats prior to dietary intervention. Compared with the soy-free diet, cats that received the soy diet had significantly higher total thyroxine (T4) and free T4 (fT4) concentrations, but unchanged total triiodothyronine (T3) concentrations. The T3/fT4 ratio was also significantly lower in cats that received the soy diet. Although the magnitudes of the increases were small (8% for T4 and 14% for fT4), these changes resulted in an increased proportion of cats (from 1/18 to 4/18) that had fT4 values greater than the upper limit of the laboratory reference range. There was no significant effect of diet on any other measured parameter. CONCLUSIONS AND CLINICAL RELEVANCE: Short-term administration of dietary soy has a measurable although modest effect on thyroid hormone homeostasis in cats. Increase in T4 concentration relative to T3 concentration may result from inhibition of 5'-iodothyronine deiodinase or enhanced T3 clearance. Soy is a common dietary component that increases serum T4 concentration in cats.     

Identification and concentration of soy phytoestrogens in commercial dog foods

OBJECTIVE: To identify and determine the concentrations of phytoestrogens in commercial dog foods. SAMPLE POPULATION: 24 commercial dog foods, including 12 moist or dry extruded commercial dog foods that contained soybeans or soybean fractions and 12 foods without any soybean-related ingredients listed on the label. PROCEDURE: Foods were analyzed for phytoestrogen content, including 4 isoflavones (genistein, glycitein, daidzein, and biochanin A), 1 coumestan (coumestrol), and 2 lignans (secoisolariciresinol and matairesinol) by use of acid-methanol hydrolysis and high-pressure liquid chromatography with UV-absorbance detection. Phytoestrogens were identified and quantified by reference to authentic standards. RESULTS: Isoflavones, coumestans, and lignans were undetectable in diets that did not list soybean-related ingredients on the label. Only 1 of the 12 diets that included soybean or soybean fractions had undetectable concentrations of phytoestrogens and that product contained soy fiber. The major phytoestrogens were the isoflavones daidzein (24 to 615 microg/g of dry matter) and genistein (4 to 238 microg/g of dry matter). CONCLUSIONS AND CLINICAL RELEVANCE: Soybean and soybean fractions are commonly used ingredients in commercial dog foods. Dietary intake of phytoestrogens may have both beneficial and deleterious health effects. Our results indicated that certain commercial dog foods contain phytoestrogens in amounts that could have biological effects when ingested long-term.     

Preliminary pharmacokinetics and cardiovascular effects of fenoldopam continuous rate infusion in six healthy dogs

Fenoldopam is a selective dopamine-1 receptor agonist that causes peripheral arterial vasodilation, increased renal blood flow, and diuresis. Enthusiasm exists for the use of fenoldopam in nonpolyuric kidney injury in dogs, although pharmacokinetic data are lacking. The purpose of this study was to collect basic pharmacokinetic and hemodynamic effect data for fenoldopam when administered to healthy awake dogs. Six healthy, awake beagles were given a 180-min fenoldopam constant rate infusion at 0.8 μg/kg per minute followed by a 120-min washout period. Citrated blood was collected during and after infusion for the measurement of plasma fenoldopam concentration by HPLC with mass spectrometry. Heart rate and indirect systolic blood pressure were concurrently measured. Mean ± SD, steady-state plasma fenoldopam concentrations of 20 ± 17 ng/mL were achieved within 10 min of starting the infusion. Area under the plasma concentration-time curve was 3678 ± 3030 ng/mL · min, and plasma clearance was 66 ± 43 mL/min per kg. Elimination was rapidly achieved in all dogs. Heart rate and systolic blood pressure were unaffected by the fenoldopam infusion. Based on the results of this study, further evaluation of the effects of fenoldopam in dogs at differing doses and in dogs with clinical conditions such as acute nonpolyuric kidney injury is warranted.