In vitro investigation of a terbinafine impregnated subcutaneous implant for veterinary use.

A terbinafine impregnated subcutaneous implant was evaluated to determine if drug was released into isotonic saline over the course of 6 months at two different temperatures, 37°C and 4°C. These temperatures were chosen to simulate the nonhibernating (37°C) and hibernating body (4°C) temperatures of little brown bats (Myotis lucifugus). Insectivorous bats of North America, including little brown bats, have been devastated by white nose syndrome, a fungal infection caused by Geomyces destructans. No treatments exist for bats infected with G. destructans. Implants were placed into isotonic saline; samples were collected once per week and analyzed with HPLC to determine terbinafine concentrations. The mean amount of terbinafine released weekly across the 28 weeks was approximately 1.7 µg at 4°C and 4.3 µg at 37°C. Although significant differences in the amount released did occur at some time points, these differences were not consistently greater or less at either of the temperatures. This study showed that terbinafine was released from an impregnated implant over the course of 6 months at concentrations ranging from 0.02 to 0.06 µg/mL depending on temperature, which may be appropriate for little brown bats (Myotis lucifugus) infected with Geomyces destructans, the etiologic agent of white nose syndrome.

Determination of bromide in canine plasma using ion chromatography.

A new ion chromatographic procedure has been developed and validated for the determination of bromide in canine plasma. Following a simple dilution, samples were separated on a Metrosep A Supp 5 column. The mobile phase was an isocratic mixture of 2.2 mM Na(2)CO(3), 1.0 mM NaHCO(3), and 1% acetonitrile, with a flow-rate of 0.7 ml/min. The procedure produced a linear curve over the concentration range of 50-2500 microg/ml. The development of the assay permitted the determination of therapeutic levels after oral administration of potassium bromide to dogs being treated for epilepsy.

Allometric scaling of marbofloxacin, moxifloxacin, danofloxacin and difloxacin pharmacokinetics: a retrospective analysis.

The purpose of this study was to examine the allometric analyses of marbofloxacin, moxifloxacin, danofloxacin and difloxacin using pharmacokinetic data from the literature. The parameters of interest (half-life, clearance and volume of distribution) were correlated across species as a function of body weight using an allometric approach (Y = aWb). Results of the allometric analysis indicated similarity between clearance and volume of distribution as they relate to body weight for all drugs. The elimination half-life was independent of body mass for all fluoroquinolones except moxifloxacin. Results of the analysis suggest that allometric scaling can be used as a tool for predicting pharmacokinetic parameters for fluoroquinolones.

Effects of L-asparaginase on plasma amino acid profiles and tumor burden in cats with lymphoma.

BACKGROUND: L-Asparaginase (Elspar(a)), is an Escherichia coli-derived enzyme that depletes lymphoma cells of asparagine, inhibiting protein synthesis and resulting in cell death. The single agent response rate in cats with lymphoma and impact of L-asparaginase on plasma amino acid concentrations is unknown. HYPOTHESES: L-Asparaginase significantly reduces plasma asparagine concentrations and has demonstrable efficacy against untreated lymphoma in cats. ANIMALS: Thirteen cats with confirmed lymphoma (LSA) of any anatomic site were given 1 dose 400 IU/kg IM) of L-asparaginase for initial LSA treatment. METHODS: Plasma collected at 0, 2, and 7 days after L-asparaginase therapy was assayed for ammonia, asparagine, aspartic acid, glutamine, and glutamic acid concentrations. Cats were restaged 7 days later to assess tumor response. RESULTS: Eight cats had T-cell LSA, 4 cats had B-cell LSA, and 1 cat's immunophenotype was unknown. Two complete and 2 partial responses to L-asparaginase were seen. Four cats had stable disease, and 5 cats had progressive disease. Ammonia and aspartic acid concentrations were increased from baseline at 2 and 7 days posttreatment. Asparagine concentrations were decreased from baseline at 2 days but not 7 days posttreatment. Glutamic acid concentrations were increased at day 2 compared to day 7 posttreatment but not compared to baseline. Glutamine concentrations were unchanged. CONCLUSIONS AND CLINICAL IMPORTANCE: L-asparaginase significantly reduced asparagine concentrations within 2 days of treatment, but this effect was lost within 7 days. The apparent overall response rate of feline LSA to L-asparaginase in this study was 30%.

Allometric analysis of ciprofloxacin and enrofloxacin pharmacokinetics across species.

The purpose of this study was to examine the allometric analysis of ciprofloxacin and enrofloxacin using pharmacokinetic data from the literature. The pharmacokinetic parameters used were half-life, clearance and volume of distribution. Relationships between body weight and the pharmacokinetic parameter were based on the empirical formula Y = aW(b), where Y is half-life, clearance or volume of distribution, W the body weight and a is an allometric coefficient (intercept) that is constant for a given drug. The exponential term b is a proportionality constant that describes the relationship between the pharmacokinetic parameter of interest and body weight. A total of 21 different species of animals were studied. Results of the allometric analyses indicated similarity between clearance and volume of distribution as they related to body weight for both drugs. Results of the current analyses indicate it is possible to use allometry to predict pharmacokinetic variables of enrofloxacin or ciprofloxacin based on body size of species. This could provide information on appropriate doses of ciprofloxacin and enrofloxacin for all species.

Plasma-Saturating intakes of vitamin C confer maximal antioxidant protection to plasma.

OBJECTIVE: Supplemental vitamin C has been shown to reduce oxidative damage in vivo, yet the dose-response relationship between vitamin C intake and antioxidant protection is not known. This report examined blood indicators of oxidative stress in subjects consuming graded doses of vitamin C, from 75 to 2,000 mg/day. METHODS: Ten healthy, non-smoking men and women (26.1 +/- 2.1 years) were recruited from a campus population. During the ten-week study, subjects limited fruit and vegetable consumption (< or = 3 servings/day) and consumed a multivitamin and mineral pill daily. Beginning at week 3, subjects ingested either a vitamin C (n = 8) or placebo (n = 2) capsule, which were identical in appearance and taste. The content of the vitamin C capsule increased every two weeks (from 250 mg at weeks 3-4 to 500 mg, 1,000 mg. and 2,000 mg at weeks 5-6. 7-8. 9-10, respectively). Fasting blood samples were collected at two-week intervals and analyzed for vitamin C, total lipid hydroperoxides and Heinz bodies in packed erythrocytes incubated 24 hours at 37 degrees. RESULTS: Plasma vitamin C rose 55% in vitamin C-supplemented subjects by the end of the ten-week treatment (p < 0.05), and measures of oxidative stress decreased 60% to 90% (8.1 +/- 0.6 to 3.5 +/- 0.4 nmol/mL and 69.1 +/- 7.8% to 6.7 +/- 6.0% for total lipid hydroperoxides and Heinz bodies, respectively). Significant decreases in markers of oxidative stress were noted at the 500 mg, 1,000 mg and 2,000 mg dosages versus placebo. Antioxidant protection was similar at the 1,000 mg and 2,000 mg dosage. CONCLUSIONS: These data indicate that the antioxidant protection afforded by short-term vitamin C supplementation is maximal at the 500-1,000 mg dosage range.

Determination of cefoxitin in serum and tissue.

A simple, rapid and sensitive method for the clean-up and analysis of cefoxitin in serum and tissue is described. Serum (0.5 ml) and tissue (100 mg) samples after homogenization underwent high speed centrifugation. Chromatography was performed on a muBondapak C18 cartridge using a mobile phase of 0.005 M potassium dihydrogen phosphate-acetonitrile-glacial acetic acid (77.5:22:0.5, v/v/v) with a flow-rate of 2.0 ml/min. Ultraviolet detection occurred at 235 nm. The procedure produced a linear curve for the concentration range 100-5000 ng/ml. The assay produced accurate, repeatable and rapid results for both tissue and serum samples without the need for chemical extraction.

Effect of infusion regime on doxorubicin pharmacokinetics in the cat.

In the pharmacokinetic evaluation of a single doxorubicin dose calculated by body surface area (25 mg/m2) or body weight (1 mg/kg body weight) and given intravenously as a 10-, 15-, or 20-minute infusion, the rate of doxorubicin infusion (mg per minute per m2 or mg per minute per kg) correlated positively with clearance and the distribution rate constant alpha, and it inversely correlated with area under the plasma concentration versus time curve (AUC). These findings suggest that a slower infusion rate results in a greater AUC and longer distribution phase than a faster infusion rate and indicates the importance of normalizing dosage regimes by infusion rate rather than by infusion duration when considering dose-response phenomena in veterinary patients.

Microassay for determination of itraconazole and hydroxyitraconazole in plasma and tissue biopsies.

A simple, rapid and sensitive method for the extraction and HPLC analysis of itraconazole and hydroxyitraconazole in tissue and plasma or serum is described. Tissue (5-100 mg) and plasma (0.1 ml) underwent a simple extraction into methanol. Chromatography was performed on a Novapak C18 column using a mobile phase of water-acetonitrile-diethylamine (42:58:0.05, v/v), pH 2.45, with a flow-rate of 1.5 ml/min. Fluorescence was measured at excitation 260 nm and emission 365 nm. The procedure produced a linear curve for the concentration range 10-1000 ng/ml. The development of the assay produced accurate, rapid repeatable results for both tissue and plasma or serum.

The toxicokinetics of 1,3-butylene glycol versus ethanol in the treatment of ethylene glycol poisoning.

Ethylene glycol (EG) is a toxic chemical found in antifreeze and heat exchangers. Standard therapy for EG intoxication in administration of ethanol (ETOH) to inhibit its metabolism by alcohol dehydrogenase (ADH). Studies indicate 1,3-butylene glycol (BG) binds to ADH more efficiently than EG and is orally less toxic than EG or ETOH. Male rats were divided into 5 groups of 6 animals. Groups received by oral intubation a single dose of EG (32 mmole/kg), BG (39 mmole/kg) initially and every 6 h up to 72 h, ETOH (39 mmole/kg) initially and every 6 h up to 72 h, or EG initially and then either BG or ETOH every 6 h up to 72 h. Administration of ETOH produced hepatotoxicity and pulmonary pathology as indicated by changes in clinical chemistry, urinalysis, and histopathology, while BG did not. Neither ETOH nor BG produced any apparent nephrotoxicity. ETOH produced ataxia, lethargy and central nervous system depression while BG did not. BG produced a higher concentration of urinary EG indicating a better inhibition of ADH metabolism of EG. Ethanol produced a higher EG blood concentration than BG. Ethanol's higher EG blood concentration may be partially attributed to dehydration and a decreased urine output as well as inhibition of ADH metabolism. Ethanol produced mortality in all animals prior to 72 h. The EG/ETOH combination produced mortality more quickly due to additive toxicity of the combination. Lack of any significant toxicity produced by BG and the production of significant toxicities by ETOH indicates that BG is potentially a better antidote than ETOH.

Determination of adriamycin in plasma and tissue biopsies.

A simple, rapid and sensitive method for the extraction and high-performance liquid chromatographic analysis of adriamycin in tissue and plasma is described. Tissue (5-100 mg) and plasma (1 ml) samples underwent a C18 Sep-Pak extraction into methanol. Chromatography was performed on a muBondapakphenyl column using a mobile phase of acetonitrile-0.1 M ammonium formate (pH 4.0) with a flow-rate of 2 ml/min. Fluorometric detection was used with an excitation of 480 nm and an emission of 550 nm. The procedure produced a linear curve for the concentration range 25-1000 ng/ml. The development of the assay produced rapid, repeatable and accurate results for both small tissue samples and plasma.

Experimental aerobic-anaerobic thoracic empyema in the guinea pig.

The clinical and pathological features of experimental aerobic-anaerobic thoracic empyema in the Duncan-Harley guinea pig are described. Thoracic empyema development and early death (less than 14 days after bacterial inoculation) were noted after various concentrations and species were inoculated into the pleural space with a piece of umbilical tape, which was used as a cofactor. The effect of concomitant hemothorax was also tested. Gram-negative infection was found to have a more virulent course than Gram-positive infection in the thoracic cavity. Moreover, these findings support the thesis that intrathoracic inoculation of anaerobic bacteria, even in combination with other anaerobic species, fails to produce clinical empyemas. However, anaerobic bacteria appear to enhance synergistically the virulence of sublethal and subempyema-forming concentrations of aerobic bacteria such as Staphylococcus aureus and Escherichia coli.

Chronic cutaneous infection caused by Mycobacterium intracellulare.

A 53-year-old woman had multiple ulcerative skin lesions caused by Mycobacterium intracellulare. The original lesions had appeared on her face and upper part of her chest at least 11 years earlier and had progressed slowly to involve large areas of her head and trunk. This unusual skin infection demonstrates chronicity and destructiveness.

Calculations of the variability of ice cloud radiative properties at selected solar wavelengths.

This study shows that there is surprising little difference in values of reflectance, absorptance, and transmittance for many of the intermediate-size particle spectra. Parrticle size distributions with mode radii ranging from approximately 50 to 300 microAm, irrespective of particle shape and nearly independent of the choice of size distribution representation, give relatively similar flux values. The very small particle sizes, however, have significantly larger values of reflectance and transmittance with corresponding smaller values of absorptance than do the larger particle sizes. The very large particle modes produce very small values of reflectance and transmittance along with very large values of absorptance. Such variations are particularly noticeable when plotted as a function of wavelength.

Nonspherical extinction and absorption efficiencies.

Predictions concerning the scattering and absorption characteristics of electromagnetic radiation interacting with nonspherical particles are obtained by suppression of particle resonances (surface waves) in classical Mie scattering theory. The importance of the particle resonance phenomenon and thus the nonspherical corrections is related to the three classical variables n(i), n(r), and x, the imaginary and real components of the index of refraction and the size parameter, respectively. The resonance phenomenon becomes increasingly restricted to small values of x as n(r) increases. For solar wavelengths and cloud size particles resonance phenomenon may be neglected for n(r) greater, similar 2. As n(r), decreases the effect of nonsphericity becomes increasingly significant to both scattering and absorption. For n(r) less, similar 2.0 and n(i) approximately 10(-5), suppression of particle resonances in Mie theory predicts increases in absorption efficiency of several orders of magnitude in the region of the absorption peak.