Detection, quantification, and pharmacokinetics of furosemide and its effects on urinary specific gravity following IV administration to horses

Furosemide is a potent loop diuretic used for the prevention of exercise-induced pulmonary hemorrhage in horses. This drug may interfere with the detection of other substances by reducing urinary concentrations, so its use is strictly regulated. The regulation of furosemide in many racing jurisdictions is based on paired limits of urinary SG (<1.010) and serum furosemide concentrations (>100 ng/ml). To validate this regulatory mechanism, a liquid chromatography/mass spectrometry/mass spectrometry method employing a solid-phase extraction procedure and furosemide-d5 as an internal standard was developed. The method was used to determine the pharmacokinetic parameters of furosemide in equine serum samples and its effects on urinary SG after IV administration (250 mg) to 10 horses. Pharmacokinetic analysis showed that serum concentrations of furosemide were well described by a two-compartmental open model. Based on results in this study, it is very unlikely for horses to have serum furosemide concentrations greater than 100 ng/ml or urine SG less than 1.010 at 4 hours after administration (250 mg IV). However, it should be remembered that urine SG is a highly variable measurement in horses, and even without furosemide administration, some horses might naturally have urine SG values less than 1.010.     

Lidocaine in the horse: its pharmacological effects and their relationship to analytical findings

Lidocaine is a local anaesthetic agent that is widely used in equine medicine. It is also an Association of Racing Commissioners International (ARCI) Class 2 foreign substance that may cause regulators to impose substantial penalties if residues are identified in post race urine samples. Therefore, an analytical/pharmacological database was developed for this drug. Using our abaxial sesamoid local anaesthetic model, the highest no-effect dose (HNED) for the local anaesthetic effect of lidocaine was determined to be 4 mg. Using enzyme-linked immunosorbent assay (ELISA) screening, administration of the HNED of lidocaine to eight horses yielded peak serum and urine concentrations of apparent lidocaine of 0.84 ng/mL at 30 min and 72.8 ng/mL at 60 min after injection, respectively. These concentrations of apparent lidocaine are readily detectable by routine ELISA screening tests (LIDOCAINE ELISA, Neogen, Lexington, KY). ELISA screening does not specifically identify lidocaine or its metabolites, which include 3-hydroxylidocaine, dimethylaniline, 4-hydroxydimethylaniline, monoethylglycinexylidine, 3-hydroxymonoethylglycinexylidine, and glycinexylidine. As 3-hydroxylidocaine is the major metabolite recovered from equine urine, it was synthesized, purified and characterized, and a quantitative mass spectrometric method was developed for 3-hydroxylidocaine as recovered from horse urine. Following subcutaneous (s.c.) injection of the HNED of lidocaine, the concentration of 3-hydroxylidocaine recovered from urine reached a peak of about 315 ng/mL at 1 h after administration. The mean pH of the 1 h post dosing urine samples was 7.7, and there was no apparent effect of pH on the amount of 3-hydroxylidocaine recovered. Within the context of these experiments, the data suggests that recovery of less than 315 ng/mL of 3-hydroxylidocaine from a post race urine sample is unlikely to be associated with a recent local anaesthetic effect of lidocaine. Therefore these data may be of assistance to industry professionals in evaluating the significance of small concentrations of lidocaine or its metabolites in postrace urine samples. It should be noted that the quantitative data are based on analytical methods developed specifically for this study, and that methods used by other laboratories may yield different recoveries of urine 3-hydroxylidocaine.     

Milk and serum concentration of ceftiofur following intramammary infusion in goats

Five dairy goats were used to determine the milk and serum concentrations along with elimination characteristics of ceftiofur following intramammary administration. One udder half of each goat was infused twice with 125 mg ceftiofur with a 24‐h interval between infusions. Milk samples were collected at 1, 2, 8, and 12 h after the last infusion and then every 12 h for a total of 7 days. Blood was collected from each animal at 3, 8, 12, and 24 h after infusion and then every 24 h for 6 days. Following a washout period of 1 week, the experiment was repeated using the opposite udder half. The elimination half‐life of ceftiofur from the mammary gland was 4.7 h. The concentration of ceftiofur was greater than published MIC₉₀ values for Staphylococcus spp. bacteria for 24 h. Ceftiofur was absorbed into systemic circulation from the mammary gland. The maximum concentration was 552 ng/mL at 3 h after infusion, and the serum elimination half‐life was 10 h. Intramammary infusion of 125 mg ceftiofur every 24 h can be expected to maintain drug concentration in milk above published MIC₉₀ for Staphylococcus spp.     

Determination of Heat Requirements and Effective Heat Summations of Some Pomegranate Cultivars Grown in Southern Anatolia

Temperature (high and low) is one of the most limiting environmental factors for growth and production of fruits in different parts of the world. For temperate-zone fruit species, a certain total heat requirements are needed in order to obtain ripe fruits. The aim of this study was to determine heat requirements of three commercial pomegranate cultivars (‘Suruc’, ‘Katirbasi’ and ‘Hicaznar’) grown in Southern Anatolia region. The cultivars showed a narrower range of heat requirements for flowering (growing degree hours, GDH), i.e. ‘Suruc’ (25,000), ‘Katirbasi’ (25,270), ‘Hicaznar’ (28,000) and a wide range of heat requirements for fruit ripening, i.e. ‘Suruc’ (73,670), ‘Katirbasi’ (74,105) and ‘Hicaznar’ (88,052) GDH. Under the Sanliurfa province conditions, two years average of effective heat summation requirement from bud swelling to 50 % flowering stage for ‘Suruc’, ‘Katirbasi’ and ‘Hicaznar’ cultivars are calculated as 643, 655 and 718 growing degree days (GDD) and from bud swelling to harvest are 2734, 2802 and 3289 GDD. It can be concluded that the effective heat summation of Sanliurfa province is enough for commercial growing for all pomegranate cultivars.     

Acaricidal effects of the essential oil of Origanum minutiflorum (Lamiaceae) against Rhipicephalus turanicus (Acari: Ixodidae)

The acaricidal effects of the volatile essential oil Origanum minutiflorum O. Schwarz & P.H. Davis (Lamiaceae) against adult Rhipicephalus turanicus was evaluated at a variety of concentrations and exposure times. Generally tick mortality increased with concentration and exposure. Ticks exposed to vapors from cotton wicks containing at least 10 μl/L resulted in complete (100%) mortality at 120 min. The major constituent of essential oil obtained from the plant material of O. minutiflorum was carvacrol.     

Genetic variation and environmental stability of grain mineral nutrient concentrations in <Emphasis Type="Italic">Triticum dicoccoides</Emphasis> under five environments

Nineteen wild emmer wheat [Triticum turgidum ssp. dicoccoides (Körn.) Thell.] genotypes were evaluated for the grain concentrations of phosphorous (P), potassium (K), sulfur (S), magnesium (Mg), calcium (Ca), zinc (Zn), manganese (Mn), iron (Fe) and cooper (Cu) under five different environments in Turkey and Israel. Each mineral nutrient has been investigated for the (1) genotype by environment (G × E) interactions, (2) genotype stability, (3) correlation among minerals and (4) mineral stability. Among the macronutrients analyzed, grain concentrations of Ca (range 338–2,034 mg kg^?1) and S (range 0.18–0.43%) showed the largest variation. In the case of micronutrients, the largest variation was observed in the grain Mn concentration (range 13–87 mg kg^?1). Grain concentrations of Fe and Zn also showed important variation (range 27–86 and 39–115 mg kg^?1, respectively). Accessions with higher nutrient concentrations (especially Zn and Fe) had also greater grain weight, suggesting that higher grain Zn and Fe concentrations are not necessarily related to small grain size or weight. Analysis of variance showed that environment was the most important source of variation for K, S, Ca, Fe, Mn and Zn, explaining between 44 and 78% of the total variation and G × E explained between 20 and 40% of the total variation in all the minerals, except for S and Zn where its effect accounted for less than 16%. Genotype was the most important source of variation for Cu (explaining 38% of the total variation). However, genotype effect was also important for Mg, Mn, Zn and S. Sulfur and Zn showed the largest heritability values (77 and 72%, respectively). Iron exhibited low heritability and high ratio value between the G × E and genotype variance components \( \left( {\sigma_{\text{GE}}^{2} /\sigma_{G}^{2} } \right) \), suggesting that specific adaptation for this mineral could be positively exploited. The wild emmer germplasm tested in the current study revealed some outstanding accessions (such as MM 5/4 and 24-39) in terms of grain Zn and Fe concentrations and environmental stability that can be used as potential donors to enhance grain micronutrient concentrations in wheats.