Evaluation of bioequivalence after oral, intramuscular, and intravenous administration of racemic ketoprofen in pigs

OBJECTIVE: To assess bioequivalence after oral, IM, and IV administration of racemic ketoprofen in pigs and to investigate the bioavailability after oral and IM administration. ANIMALS: 8 crossbred pigs. PROCEDURES: Each pig received 4 treatments in a randomized crossover design, with a 6-day washout period. Ketoprofen was administered at 3 and 6 mg/kg, PO; 3 mg/kg, IM; and 3 mg/kg, IV. Plasma ketoprofen concentrations were measured by use of high-performance liquid chromatography for up to 48 hours. To assess bioequivalence, a 90% confidence interval was calculated for the area under the time-concentration curve (AUC) and maximum plasma concentration (C(max)). RESULTS: Equivalence was not detected in the AUCs among the various routes of administration nor in C(max) between oral and IM administration of 3 mg/kg. The bioavailability of ketoprofen was almost complete after each oral or IM administration. Mean +/- SD C(max) was 5.09 +/- 1.41 microg/mL and 7.62 +/- 1.22 microg/mL after oral and IM doses of 3 mg/kg, respectively. Mean elimination half-life varied from 3.52 +/- 0.90 hours after oral administration of 3 mg/kg to 2.66 +/- 0.50 hours after IV administration. Time to peak C(max) after administration of all treatments was approximately 1 hour. Increases in AUC and C(max) were proportional when the orally administered dose was increased from 3 to 6 mg/kg. Conclusions and Clinical Relevance: Orally administered ketoprofen was absorbed well in pigs, although bioequivalence with IM administration of ketoprofen was not detected. Orally administered ketoprofen may have potential for use in treating pigs.     

Efficacy of oral and parenteral ketoprofen in lactating cows with endotoxin-induced acute mastitis

One hind quarter of 27 healthy lactating cows was infused with 100 microg Escherichia coli endotoxin. Two hours later, nine of the cows were given physiological saline by intramuscular injection, nine were given 4 mg/kg ketoprofen orally, and nine were given 3 mg/kg ketoprofen by intramuscular injection. Ketoprofen administered either orally or parenterally significantly reduced the effect of the endotoxin on rectal temperature, ruminal contractions and respiratory rate. The size of the udder, the signs of pain and the concentrations of thromboxane B2, especially in plasma, were also reduced, and the appearance of their milk was almost normal. The response of cows to the oral treatment was as rapid as it was to intramuscular treatment.     

Characterization of the Q.Ymym region on wheat chromosome 2D associated with wheat yellow mosaic virus resistance

Yellow mosaic disease, caused by wheat yellow mosaic virus (WYMV), is one of the most serious diseases of winter wheat in Japan and China. A single major QTL for WYMV resistance in the Japanese wheat variety 'Yumechikara', designated Q.Ymym, has been mapped on a 43.6 cM linkage block between the two markers Xcfd233 and Xgwm349 on chromosome 2D. We were able to obtain two recombinants within the block, which facilitated reducing the size of the linkage block. The pseudomolecule sequence of 'Chinese Spring' (CS) indicated that the original Q.Ymym region of 43.6 cM corresponded to 68.5 Mb and the narrowed Q.Ymym region represents a size of 27.3 Mb. The sequence features of the Q.Ymym region were unique in comparison with CS sequences, which may have led to the low recombination rate within the block. The Q.Ymym haplotype block was detected in other WYMV-resistant varieties but not in the susceptible varieties used in this study. The unique sequence structure of the Q.Ymym region allowed the development of co-dominant markers for use in marker-assisted selection.     

Molecular basis of proton motive force generation: structure of formate dehydrogenase-N

The structure of the membrane protein formate dehydrogenase-N (Fdn-N), a major component of Escherichia coli nitrate respiration, has been determined at 1.6 angstroms. The structure demonstrates 11 redox centers, including molybdopterin-guanine dinucleotides, five [4Fe-4S] clusters, two heme b groups, and a menaquinone analog. These redox centers are aligned in a single chain, which extends almost 90 angstroms through the enzyme. The menaquinone reduction site associated with a possible proton pathway was also characterized. This structure provides critical insights into the proton motive force generation by redox loop, a common mechanism among a wide range of respiratory enzymes.     

Foliar potassium status explains douglas fir response to nitrogen fertilization in the Inland Northwest,USA

Despite apparently inadequate N levels throughout the Inland Northwest of the United States, trees on some sites showed no increased growth 6 yr after N fertilization. Nor did higher N application rates consistently produce higher response. These facts indicated that other factors are limiting tree growth at these sites. Results suggest that K status is one important factor, influencing N fertilization response in the following general ways: (1) for stands with low pretreatment foliar K levels, the amount and duration of growth response are reduced, and higher N fertilizer rates produce less response; and (2) for all stands, growth response declines when foliar K decreases after N fertilization.     

The Dnmt3b splice variant is specifically expressed in in vitro-manipulated blastocysts and their derivative ES cells

Manipulation of preimplantation embryos in vitro, such as in vitro fertilization (IVF), in vitro culture (IVC), intracytoplasmic sperm injection (ICSI), somatic cell nuclear transfer (SCNT) and other assisted reproduction technologies (ART), has contributed to the development of infertility treatment and new animal reproduction methods. However, such embryos often exhibit abnormal DNA methylation patterns in imprinted genes and centromeric satellite repeats. These DNA methylation patterns are established and maintained by three DNA methyltransferases: Dnmt1, Dnmt3a and Dnmt3b. Dnmt3b is responsible for the creation of methylation patterns during the early stage of embryogenesis and consists of many alternative splice variants that affect methylation activity; nevertheless, the roles of these variants have not yet been identified. In this study, we found an alternatively spliced variant of Dnmt3b lacking exon 6 (Dnmt3bΔ6) that is specific to mouse IVC embryos. Dnmt3bΔ6 also showed prominent expression in embryonic stem (ES) cells derived from in vitro manipulated embryos. Interestingly, IVC blastocysts were hypomethylated in centromeric satellite repeat regions that could be susceptible to methylation by Dnmt3b. In vitro methylation activity assays showed that Dnmt3bΔ6 had lower activity than normal Dnmt3b. Our findings suggest that Dnmt3bΔ6 could induce a hypomethylation status especially in in vitro manipulated embryos.     

Proteome analysis of whole and water‐soluble proteins in masseter and semitendinosus muscles of Holstein cows

To assess both quantitative and qualitative differences between the slow‐ and fast‐type muscles, masseter (slow) and semitendinosus (fast) from four Holstein cows were analyzed by two‐dimensional difference gel electrophoresis (2D DIGE) and mass spectrometry. The proteome analysis identified 27 spots as 20 proteins in the whole protein fraction extracted with 8 mol/L urea solution, and 16 spots were identified as 11 proteins in the water‐soluble protein fraction. Two slow‐type myofibrillar proteins (myosin light chain‐1 slow‐b and myosin light chain‐2 slow), and aconitase‐2 mitochondria were present at higher levels in the masseter muscle (P < 0.05). Four fast‐type myofibrillar proteins (myosin light chain‐1 fast, myosin light chain‐2 fast, myosin light chain‐3 fast and tropomyosin‐1), and three enzymes of glycolytic pathway (enolase‐3, aldolase‐A and triosephosphate isomerase), were present at higher levels in the semitendinosus muscle (P < 0.05). Our proteome analysis showed that the composition of sarcoplasmic proteins as well as myofibrillar proteins was clearly different between slow‐ and fast‐type muscles.