Characterization of the relationship between serum and milk residue disposition of ceftriaxone in lactating ewes

The present study was planned to investigate the serum disposition kinetics and the pattern of ceftriaxone elimination in milk and urine of lactating ewes (n = 6) following i.v. and i.m. administration. A crossover study was carried out in two phases separated by 15 days. Ceftriaxone was administered at a dosage of 10 mg/kg b.w. in all animals. Serum, milk and urine samples were collected between 0 and 72 h and a modified agar diffusion bioassay method was used to determine the percentage of protein binding and to measure serum, urine and milk concentrations of ceftriaxone. The drug was detected between 5 min and 48 h postdosing. Concentrations of 0.56 (10 h) and 0.52 (12 h), 0.22 (10 h) and 0.19 (12 h), and 2.18 (24 h) and 2.11 (48 h) mug/mL were measured in serum, milk and urine following i.v. and i.m. administration, respectively. Individual pharmacokinetic parameters were determined by fitting a two-compartment model to the serum and one-compartment open model to the milk concentration-time profiles. After i.v. dosing, the elimination rate constant and elimination half-life were 0.4 +/- 0.05/h and 1.75 +/- 0.02 h, respectively. The volume of distribution at steady state (V(dss)) of 0.28 +/- 0.15 L/kg reflected limited extracellular distribution of the drug with total body clearance (Cl(tot)) of 0.14 +/- 0.10 L/h/kg. Following i.m. administration, the mean T(max obs), C(max obs), t(1/2el) and AUC values for serum data were: 0.75 h, 23.16 +/- 2.94 microg/mL, 1.77 +/- 0.24 h and 67.55 +/- 6.51 microgxh/mL, respectively. For milk the data were: 1.0 h, 8.15 +/- 0.71 mug/mL, 2.2 +/- 0.34 h and 26.6 +/- 5.14 microgxh/mL, respectively. The i.m. bioavailability was 83.6% and the binding percentage of ceftriaxone to serum protein was 33%. Concentrations of ceftriaxone in milk produced by clinically normal mammary glands of ewes were consistently lower than in serum; the kinetic value AUC(milk)/AUC(serum) and C(max milk)/C(max serum) ratios was<0.4. These low values indicated poor distribution and penetration of ceftriaxone from the bloodstream to the mammary gland of lactating ewes following both routes.     

Export rate of dissolved organic matter from paddy fields during cultivation-activity events

The aim of this study is to quantify the dissolved organic carbon (DOC) of drainage water from paddy fields in agricultural areas of Tottori prefecture, Japan. In four experimental paddy fields, DOC concentration varied much from 1.1 to 10.1 mg C l⁻¹, and was the highest during heavy runoff that occurred in April when there was a non-agricultural period. However, variation in DOC concentration did not always correspond to rainfall, but depended more on cultivation-activity events such as tilling, planting, draining in summer, and final draining in autumn. The water discharge rate from each experimental field was estimated by using a hydrologic model (the Tank Model and a genetic algorithm). Daily DOC export rate per unit area of three experimental paddy fields was calculated to be 0.0074, 0.0052, and 0.0081 kg a⁻¹ day⁻¹, respectively. The daily DOC export rate showed large seasonal variation with the highest value in May and June. It can be concluded that DOC export from paddy fields can be a substantial source of DOC in receiving waters, and the export rate depends much on cultivation method practice. It might be suggested that DOC export from paddy fields can be controlled by a better water management practice of farmers.     

Atmospheric Deposition of Nitrogen and Sulfur in the Yellow Sea Region: Significance of Long-Range Transport in East Asia

The amounts of nitrogen and sulfur deposited in the region of the Yellow Sea in both dry and wet forms were estimated focusing on the period between 1999 and 2000. Dry deposition fluxes were obtained using concentrations from ground stations on both Korean and Chinese sides and from shipboard and aircraft measurements. Wet deposition fluxes were determined at ground stations on the Korean side. The dry deposition flux over the Yellow Sea was much greater than those for other world oceans. As a whole, the amounts of wet depositions of nitrogen and sulfur were 1.9 and 1.5 times larger than the amounts of respective dry depositions. Substantial influence from China caused by high emissions in East China and westerly wind was possibly suggested. However, the influence from nitrogen emission in Korea was also confirmed.     

Evaluation of F1 and BC1 hybrids of Lilium lancifolium × Asiatic hybrid ‘Chianti’ by morphological analysis and fluorescence in situ hybridization

Lilium lancifolium Thunb. exhibits wide genetic diversity and numerous genetic traits within progeny populations. Parent morphology affects the distribution and assortment of progeny phenotypes. In this study, morphological analysis and fluorescence in situ hybridization (FISH) were conducted for cross progeny (F1 and BC1). Results showed that F1-1 hybrids had greater plant height than the parents; however, backcross progeny plant height (group 1) was low. Leaf number in both groups was considerably low in F1 hybrid, although high in backcrossed plants. Flower number and days to flower opening were intermediate to those of the parents for F1 hybrids, yet low in BC1 progeny. In group 1, backcross progeny showed small bulb length; however, group 2 progeny showed large bulb length. Positive and negative correlations between the phenotypic traits of parents and progeny confirmed significant variations. According to FISH results, F1-1 and F1-2 hybrids distinctly exhibited nine and eight 45S rDNA loci which were same in position with 45S loci of the parents. In backcross progeny, eight 45S rDNA signals were detected in four BC1 progeny of group 1, while 10 signals were observed in all group 2 progeny, same with the L. lancifolium karyotype. Morphological analysis and FISH helped in scrutinising progeny to obtain hybrids with desirable characteristics.     

Phytotoxic activity of clomeprop in soil and concentration of its hydrolysed metabolite DMPA in soil water

The relationship between the fate of clomeprop in soil and its phytotoxic activity on the growth of radish (Raphanus sativus) seedlings was investigated in the laboratory. The phytotoxic activity of clomeprop in sea sand was much higher than in non-autoclaved soil, and the phytotoxic activity in non-autoclaved soil was higher than in autoclaved soil. The phytotoxic activity of 2-(2,4-dichloro-3-methylphenoxy)propionic acid (DMPA), a hydrolysed metabolite of clomeprop, was higher than that of the latter under both soil conditions. Clomeprop was adsorbed on soil to a greater extent than DMPA. The concentration of clomeprop in soil water of non-autoclaved soil decreased with increase of the DMPA concentration in the soil water in a time-dependent manner. It is suggested that the phytotoxic activity of clomeprop applied to soil is induced mostly by the DMPA concentration in soil water after hydrolytic degradation by soil microbes. © 1999 Society of Chemical Industry     

Rapid NMR method for the quantification of organic compounds in thin stillage

Thin stillage contains organic and inorganic compounds, some of which may be valuable fermentation coproducts. This study describes a thorough analysis of the major solutes present in thin stillage as revealed by NMR and HPLC. The concentration of charged and neutral organic compounds in thin stillage was determined by excitation sculpting NMR methods (double pulse field gradient spin echo). Compounds identified by NMR included isopropanol, ethanol, lactic acid, 1,3-propanediol, acetic acid, succinic acid, glycerophosphorylcholine, betaine, glycerol, and 2-phenylethanol. The concentrations of lactic and acetic acid determined with NMR were comparable to those determined using HPLC. HPLC and NMR were complementary, as more compounds were identified using both methods. NMR analysis revealed that stillage contained the nitrogenous organic compounds betaine and glycerophosphorylcholine, which contributed as much as 24% of the nitrogen present in the stillage. These compounds were not observed by HPLC analysis.     

Parvalbumin‐immunoreactive cells in the olfactory bulb of the pigeon: Comparison with the rat

The olfactory bulb (OB) shows special characteristics in its phylogenetic cortical structure and synaptic pattern. In the OB, gamma‐aminobutyric acid (GABA), as an inhibitory neurotransmitter, is secreted from GABAergic neurons which contain parvalbumin (a calcium‐binding protein). Many studies on the distribution of parvalbumin‐immunoreactive neurons in the rodent OB have been published but poorly reported in the avian OB. Therefore, in this study, we compared the structure of the OB and distribution of parvalbumin‐immunoreactive neurons in the OB between the rat and pigeon using cresyl violet staining and immunohistochemistry for parvalbumin, respectively. Fundamentally, the pigeon OB showed layers like those of the rat OB; however, some layers were not clear like in the rat OB. Parvalbumin‐immunoreactive neurons in the pigeon OB were predominantly distributed in the external plexiform layer like that in the rat OB; however, the neurons did not have long processes like those in the rat. Furthermore, parvalbumin‐immunoreactive fibres were abundant in some layers; this finding was not shown in the rat OB. In brief, parvalbumin‐immunoreactive neurons were found like those in the rat OB; however, parvalbumin‐immunoreactive fibres were significantly abundant in the pigeon OB compared to those in the rat OB.     

Comparison of bare metal stent and paclitaxel-eluting stent using a novel rat aorta stent model

The purpose of our study was to create a novel rat aorta stent implantation model. Stainless steel bare metal stents (BMS) or paclitaxel-eluting stents (PES) were implanted in male Sprague-Dawley rats (BW 400 ± 20 g). Two and four weeks after stent implantation, the aorta were collected, fixed with 2% glutaraldehyde, and cut into two segments. One segment was used for scanning electron microscopy analysis to evaluate re-endothelialization, and the other segment was used to calculate the neointimal area. At 2 weeks after stenting, the appearance of neointimal hyperplasia was less in the PES group than in the BMS group. At 4 weeks after stenting, no significant difference in neointimal hyperplasia was observed between two groups. On the other hand, the PES group showed more thrombus formation and less re-endothelialization compared to the BMS group. This study demonstrated the ability of a novel rat model of aorta stenting via a common carotid artery to measure the efficacy and safety of commercially available drug-eluting stents.     

Acute-phase Response Alters the Disposition Kinetics of Cefepime following Intravenous Administration to Rabbits

The effect of experimentally induced fever on the pharmacokinetics of cefepime administered intravenously at a dose of 75 mg/kg bw was studied in six healthy rabbits. The study was conducted in two consecutive phases, separated by a washout period of 2 weeks. Infection was induced by the intravenous inoculation of 5 × 10⁸ cfu of Escherichia coli 24 h before the pharmacokinetic investigation was carried out. Serial blood samples for cefepime concentration determination were obtained for 48 h following drug administration. The concentrations of cefepime in the plasma were determined by a quantitative microbiological assay using an agar-gel diffusion method employing Bacillus subtilis ATCC 6633 as the test organism, with a level of detectability of approximately 0.10 μg/ml. Cefepime plasma concentrations versus time were evaluated by non-compartmental methods using WinNonLin. Cefepime was well tolerated and no serious adverse events were observed. Rectal temperature increased 1^°C 24 h post injection in infected animals. Highly significant differences in the blood plasma concentrations of cefepime were observed between febrile and healthy animals at all the sampling times. This could explain the greater area under the plasma level–time curve of the drug in febrile compared with healthy animals. The results from pharmacokinetic calculations showed that both the distribution volume at steady state (V _dss) and body clearance (CL_tot) were affected in febrile as compared to healthy animals. The mean values of V _dss and CL_tot of cefepime in healthy rabbits were 1.168 L/kg and 0.303 L/kg/h, respectively. As compared with healthy animals, the mean estimates of V _dss (0.917 L/kg) and CL_tot (0.205 L/kg per h) of cefepime were significantly lower, whereas t _1/2λ, MRT and AUMC were significantly higher in febrile rabbits. It is concluded that, although experimental infection had an effect on the disposition kinetics of cefepime in healthy and febrile rabbits, this was not sufficiently pronounced to require alteration of the dosage during disease.