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1.
Gonadotropin-releasing hormone (GnRH) antagonists are particularly useful when a rapid inhibitory effect on the gonadal axis is required. The aim of this study was to test the efficacy and clinical safety of a low and high dose of the third generation GnRH antagonist, acyline, on pregnancy termination in female dogs. The effect of the antagonist on the progesterone (P4) serum concentration was also described. Twenty-one mid-pregnant bitches were randomly assigned to a single subcutaneous (SC) dose of a placebo (PLACE; n = 7), a low (ACY-L; 110 μg/kg; n = 6) or high (ACY-H; 330 μg/kg; n = 8) dose of acyline. The animals were followed up for 15 days. All ACY treated but no placebo-treated animals terminated their pregnancy by abortion (p < 0.01). The ACY-L and ACY-H groups interrupted their pregnancy 7 ± 1.9 and 6.4 ± 1.3   days after treatment, respectively (p = 0.7). A significant interaction between treatment and day was found (p < 0.01) for P4 serum concentrations when PLACE was compared with both ACY groups. No difference was found for this hormone between both ACY groups (p > 0.05) where P4 diminished throughout the study. The decreasing rate varied among animals and was closely related to the time of abortion when P4 reached basal concentrations. In PLACE animals, gestation progressed normally and P4 did not change throughout the study (p > 0.05). None of the bitches presented side effects. It was concluded that acyline safely terminated mid-pregnancy by permanently decreasing P4 serum concentrations.  相似文献   

2.
This study was aimed at assessing the changes in sperm motion patterns and the percentage of acrosome reaction (AR) in domestic cat semen after treatment with either ionomycin or progesterone (P4). Ten ejaculates were collected from five tomcats using an artificial vagina, and were diluted, centrifuged and resuspended in a capacitation medium. Samples were evaluated and divided into seven equal aliquots and, after 2 h at 25°C, were incubated for 30 min at 38°C in 5% CO2 and then analyzed. Computer-assisted sperm analysis and a combination of three fluorescent probes were used to assess sperm plasma, acrosomal membrane integrity and mitochondrial transmembrane potential. Thirty minutes after the start of incubation, P4 was added (10 μg/ml) to the P1 group. Groups P2 and P3 were supplemented with P4 (10 and 20 μg/ml, respectively) only after 2 h of incubation, and groups I1 and I2 were supplemented with ionomycin (4 and 8 μ m , respectively) 2 h after incubation. Group E was supplemented with ethanol (0.6%) at 2 h after incubation and group C received no supplementation. Ionomycin and P4 treatments led to a hyperactivation-like sperm motion and an increase (p < 0.05) in the percentage of AR. Although a higher (p < 0.05) percentage of AR was obtained in group I2 when compared with all P4 groups, a decrease (p < 0.05) in total and progressive motility was observed in I2 group. As I1 group was similar to I2 to induce AR without diminishing sperm motility, we can conclude that ionomycin at 4 μ m seems to be more suitable to trigger AR in domestic cat sperm.  相似文献   

3.
The pharmacokinetics and pharmacodynamics of meloxicam in piglets (16–23 days old) were studied using a stratified parallel group design. One group ( n  = 13) received 0.4 mg/kg meloxicam intravenously, while the other group ( n  = 12) received physiological saline solution. A carrageenan-sponge model of acute inflammation was used to evaluate the effects of meloxicam. The plasma clearance was low (0.061 L/kg/h), the volume of distribution was low (0.19 L/kg) and the elimination half-life was short (2.7 h). At most time points, the mean concentration of meloxicam in plasma exceeded the concentrations in exudate indicating a limited accumulation of the drug at the site of the inflammation. There were significant differences between the groups in the exudate prostaglandin E2 (PGE2) concentration, but the inhibition of PGE2 in the meloxicam group was limited. The inhibition of thromboxane B2 (TXB2) production in serum in the meloxicam group was extensive, but of shorter duration than the PGE2 inhibition in exudate.  相似文献   

4.
Y. Hirano    J. Kimura    Y. Nambo    H. Yokota    S. Nakamura    S. Takemoto    R. Himeno    T. Mishima    M. Matsui    Y.-I. Miyake 《Anatomia, histologia, embryologia》2009,38(3):214-218
The structure of the equine ovary is different from that of other mammals in its extremely large size, the presence of ovarian fossa and the inverted location of its cortex and medulla. A three-dimensional internal structure microscopy (3D-ISM), which consists of a computer-controlled slicer, a CCD camera, a laser disc recorder and a PC, is very useful for the observation of the internal structures in equine ovaries. In addition, the three-dimensional images of follicles and corpus luteum (CL) reconstructed by the segmentation technique can clarify the spatial arrangement in the equine ovary. In this study, to understand the changes in the ovarian internal structures of the mare during the oestrous cycle, the size and numbers of follicles and luteal structures were analysed by 3D-ISM in addition to the concentrations of progesterone (P4) and oestradiol-17β. As a result, many small follicles (<10 mm in diameter) were detected. It was recognized that the luteal structures were distinguished into three types, such as the corpus haemorragicum (CH), which is formed by blood elements at the cavity after ovulation, CL and corpus albican (CA). There were some CHs and CL in the group, which had the concentration of P4 > 1 ng/ml. CHs were also observed in the group, which had low level of P4 (P4 < 1 ng/ml). CAs were found regardless of the P4 level. In conclusion, 3D-ISM enabled the internal observation of the ovarian structures in detail, and estimation of the stage of the ovarian cycle with complementary physiological information. The findings by 3D-ISM provide basic information for clinical applications.  相似文献   

5.
Red foxes ( Vulpes vulpes ) are a major pest species in Europe and Australia. Traditional methods of control such as hunting or poisoning are no longer sufficient or feasible. As with domestic dogs and cats, prolactin (PRL) in the vixen is an essential luteotropin during the second half of gestation. Hence, PRL inhibitors such as cabergoline have been used to induce abortions. Eighteen mated silver fox vixens (three groups of six foxes each) were treated orally with a placebo of paraffin oil (I), or with 15  μ g/kg cabergoline in feed once (II) or twice (III), on day 30 (I and II) or days 30 and 32 (III) post-coitum. Blood samples were taken prior to and after treatments and concentrations of PRL and progesterone (P4) were determined. Normal parturitions were observed in five of six, five of six and two of six vixens in groups I, II and III, respectively. In group III plasma concentrations of PRL and P4 decreased significantly but only temporarily. This drop in hormone concentrations was more pronounced in the vixens that did not carry to term. In conclusion, doses in excess of 15  μ g/kg of cabergoline are likely to prevent the development of fetuses to term in pregnant vixens.  相似文献   

6.
Prostaglandin F (PGF) and GnRH treatments given 24 h apart have been shown to result in short oestrous cycles (8–12 days) in some cows and heifers. The differences in responses may depend on the dose of GnRH. Therefore, the effect of the dose of GnRH on occurrence of short cycles and LH response was studied here. Oestrus was induced with dexcloprostenol (0.15 mg) in two groups of Ayrshire heifers. A second luteolysis was induced similarly on day 7 after ovulation; 24 h after PGF treatment, the heifers were administered either a high (0.5 mg, n = 15, group T500) or low (0.1 mg, n = 10, group T100) dose of gonadorelin. Blood samples for progesterone analyses were collected daily from the second PGF administration to the second ovulation after the PGF injection. Beginning 24 h after the GnRH treatment, ovaries were examined by transrectal ultrasonography every 6 h until ovulation, and daily between day 4 and the next ovulation. Five heifers from both groups were sampled for LH analyses via a jugular catheter every 30 min from 1 h before to 6 h after the GnRH administration. Short oestrous cycles were detected in 7 of 10 cases in group T100 and in 12 of 15 cases in group T500. No significant differences in LH responses were detected between the groups. In group T500, the rise in LH concentration tended to be somewhat slower than in group T100. The dose of GnRH (0.1 vs 0.5 mg) did not affect the occurrence of short oestrous cycles and LH response.  相似文献   

7.
The aim of this study was to describe the changes in the resistance index (RI) and systolic/diastolic ratio ( S / D ) of the uterine arteries during mid-pregnancy abortion induction in the dog. Sixteen 30–35 day pregnant bitches were randomly assigned to either a pharmacological protocol to interrupt gestation (n = 8) or were used as untreated control group (n = 8). Doppler assessments of uterine arteries blood flow were carried out before the initiation of the protocol and then every other day up to abortion (treated group) or parturition (control group). All treated bitches aborted 6 ± 1.2 days after initiation of the treatment (while none of the non-treated bitches aborted). Pre-treatment RI and S / D did not differ between groups (p > 0.2) while average post-treatment indexes were (mean ± SD): 0.62 ± 0.1 vs 0.53 ± 0.1 (p < 0.01) and 2.96 ± 0.9 vs 2.23 ± 0.3 (p = 0.01), for the treated and non-treated group respectively. Correlations between days to abortion and RI or S / D were 0.75 (p < 0.01) and 0.79 (p < 0.01) and, −0.78 (p < 0.01) and −0.73 (p < 0.01) for the treated and non-treated groups respectively. In the treated group, correlations between serum progesterone (P4) concentrations and RI and S / D were −0.76 (p < 0.01) and −0.59 (p < 0.01) respectively. It is concluded that, during induction of abortion, RI and S / D of uterine arteries progressively increased while P4 decreased.  相似文献   

8.
Phenylbutazone was administered intravenously (i.v.) to a group of four lactating cows at a dosage of 6 mg/kg body weight. Whole plasma, protein-free plasma and milk were analysed for phenylbutazone residues. Pharmacokinetic parameters of total and free phenylbutazone in plasma were calculated using a non compartmental method. In regards to whole plasma data, the mean volume of distribution at steady state ( V ss), was 147 mL/kg body weight, with a mean (± SEM) terminal elimination half-life ( t 1/2) of 40 ± 6 h. The mean clearance ( Cl ) was 3 mL/h/kg body weight. The V ss as determined from the protein-free plasma fraction was 50 021 mL/kg body weight. This larger V ss of free phenylbutazone compared to total plasma phenylbutazone was attributed to a high degree of plasma protein binding, as well as the greater penetration of free phenylbutazone into tissues. The mean t 1/2 of free phenylbutazone was 39 ± 5 h. This similarity to the t 1/2 estimated from total plasma phenylbutazone data is attributed to an equilibrium between free and plasma phenylbutazone during the terminal elimination phase. Mean t 1/2 as determined from milk, applying a urinary excretion rate model, was 47 ± 4 h. Milk clearance of phenylbutazone was 0.009 mL/h/kg body weight, or about 0.34% of total body clearance. Furthermore, evidence suggests that phenylbutazone either binds to milk proteins, or is actively transported into milk, as its concentration in milk was greater than that predicted due to a simple partitioning from plasma into milk.  相似文献   

9.
This study was performed to analyse the effects of low-protein diet (7%) on bone mass and mineral metabolism in rat pups whose mothers were submitted to protein-restricted diet during late pregnancy and early post-natal periods. For this purpose, 12 pregnant Wistar rats were divided into two groups of six animals each: a control group with free access to standard diet (20% protein) and protein-restricted group (PR) fed with low-protein diet (7% protein) from the 14th day of pregnancy until day 14 after delivery. Body weight, femur bone mass, plasma thyroid hormones (FT4 and FT3), biochemical bone marker levels [alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (ACP)] and bone DNA content were recorded. In undernourished pups, a decrease in body weight (−47%, p < 0.001) in skeletal growth (−11%, p < 0.001) and in bone DNA content (−48%, p < 0.001) were observed. Plasma protein and albumin levels and thyroid status were also decreased in undernourished rat pups compared with those of control group. The circulating amino acid levels were decreased in pups. While in their mothers, some of them were increased and the others were decreased. A positive correlation was observed between bone mass and plasma thyroid hormone levels and ALP activity and plasma protein levels, and a negative correlation with ACP activity. Plasma ALP levels were decreased by 19%, whereas plasma tartrate-resistant ACP levels were increased by 33% indicating a hyperactivity of bone remodelling. These results showed that protein-restricted diet given to mothers during late pregnancy and early post-natal periods induced changes in body weight, skeletal growth and bone metabolism in their offspring.  相似文献   

10.
Methane (CH4) is the second most important greenhouse gas (GHG) and that emitted from enteric fermentation in livestock is the single largest source of emissions in Japan. Many factors influence ruminant CH4 production, including level of intake, type and quality of feeds and environmental temperature. The objectives of this review are to identify the factors affecting CH4 production in ruminants, to examine technologies for the mitigation of CH4 emissions from ruminants, and to identify areas requiring further research. The following equation for CH4 prediction was formulated using only dry matter intake (DMI) and has been adopted in Japan to estimate emissions from ruminant livestock for the National GHG Inventory Report: Y = −17.766 + 42.793X − 0.849X2, where Y is CH4 production (L/day) and X is DMI (kg/day). Technologies for the mitigation of CH4 emissions from ruminants include increasing productivity by improving nutritional management, the manipulation of ruminal fermentation by changing feed composition, the addition of CH4 inhibitors, and defaunation. Considering the importance of ruminant livestock, it is essential to establish economically feasible ways of reducing ruminant CH4 production while improving productivity; it is therefore critical to conduct a full system analysis to select the best combination of approaches or new technologies to be applied under long-term field conditions.  相似文献   

11.
The effect of a low-selenium diet on thyroid hormone metabolism was investigated in growing kittens. Twelve specific-pathogen-free kittens with ages ranging from 16 to 18 weeks were divided into two groups of equal number with equal sex distribution in each group. One group was fed a yeast-based low-selenium diet (0.02 mg Se/kg diet) while the other group was fed the same diet supplemented with Na2SeO3 at 0.4 mg Se/kg diet for 8 weeks. Food intake, body weight and body weight gain were not affected by the low-Se diet during the study period. However, kittens given the low-Se diet had significantly reduced plasma selenium concentration and glutathione peroxidase activity. Plasma total thyroxine (T4) increased and total 3,5,3'triiodothyronine (T3) decreased significantly in kittens fed the low-Se diet at the end of the study. These results suggest that type I deiodinase in cats is a selenoprotein- or a selenium-dependent enzyme.  相似文献   

12.
Pregnancy-associated glycoprotein (PAG) concentrations were measured in buffalo cows starting from day 28 after breeding. Oestrus was synchronized in 10 buffaloes using two injections of 25 mg prostraglandin (PG)F2 α (Lutalyse®) at a 11-day interval. Blood sampling was conducted nearly twice weekly. Results indicated that plasma PAG concentrations in non-pregnant buffaloes were low (<0.20 ng/ml) during the whole experimental period (day 28 to 103), while in pregnant animals plasma PAG levels increased from day 28 (4.48 ± 0.92 ng/ml) until day 41 (27.27 ± 6.74 ng/ml), remaining high (20.71 ± 9.20 ng/ml) until day 103. Progesterone levels were significantly (p < 0.0001) higher in pregnant (3.51–4.80 ng/ml) than in non-pregnant buffaloes (0.28–1.52 ng/ml). A significant difference (p < 0.0001) in plasma PAG concentrations between pregnant and non-pregnant animals starting at day 28 after breeding suggests that PAG-radioimmunoassay could be suitable for pregnancy diagnosis in buffaloes during this period. In conclusion, PAG test offers the advantages that it requires a single plasma sample for early pregnancy diagnosis as well as the accuracy of the test for the detection of pregnancy as early as day 28.  相似文献   

13.
Myers, M. J., Scott, M. L., Deaver, C. M., Farrell, D. E., Yancy, H. F. Biomarkers of inflammation in cattle determining the effectiveness of anti-inflammatory drugs. J. vet. Pharmacol. Therap. 33 , 1–8.
The impact of nonsteroidal anti-inflammatory drugs (NSAID) on prostaglandin E2 (PGE2) production and cyclooxygenase 2 (COX-2) mRNA expression in bovine whole blood (WB) cultures stimulated by lipopolysaccharide (LPS) was determined, using the blood from six Holstein dairy cattle in various stages of lactation. Peak production of PGE2 occurred 24 h after LPS stimulation but did not result in detectable concentrations of thromboxane B2 (TXB2). The NSAID indomethacin, aspirin, flunixin meglumine, and 4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzene sulfonamide (PTPBS; celecoxib analogue), along with dexamethasone, were all equally effective in reducing the concentration of PGE2 in the bovine WB culture supernatants. Bradykinin exhibited peak supernatant concentrations 1 h after LPS stimulation. Dexamethasone and the NSAID used in this study were equally effective at inhibiting bradykinin production. Peak induction of COX-2 mRNA occurred 3 h post-LPS stimulation. However, neither dexamethasone nor any of the NSAID used in this study altered COX-2 mRNA concentrations. In contrast, aspirin, flunixin meglumine, and PTPBS reduced tumor necrosis factor-alpha (TNFα) mRNA concentration. These results demonstrate that bovine blood cells respond to NSAID therapy like other mammalian cells with respect to inhibition of PGE2 production and suppression of TNF mRNA induction, but do not inhibit induction of COX-2 mRNA.  相似文献   

14.
Improvements in human patient monitoring despite their development in animals, do not always find their way into veterinary clinical use due to financial constraints. Gastrointestinal intraluminal CO2 partial pressure (Gip1CO2) monitoring, however, is not only proving very beneficial in human trauma and critical patient care but is also very likely to become relatively inexpensive. By providing information on the perfusion adequacy of a high risk, critically important tissue, the GI mucosa, GI P1CO2 monitoring offers an easily accesible indicator of the efficacy and adequacy of resuscitative interventions. The potential for decreasing morbidity and mortality is enormous. Therefore, the practicing veterinarian should become familiar with GI P1CO2 monitoring theory and technology so he or she can be better prepared to incorporate it into practice when in becomes available.  相似文献   

15.
Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (CS0) was 112.21 ± 1.27 μg/mL and 201.43 ± 1.56 μg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC90) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 ± 2.26 μg/mL with 10 mg/kg SC and 72.14 ± 3.04 μg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC0-12/MIC90 ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC0-12/MIC90 ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.  相似文献   

16.
The objectives of this study were to determine if phenylbutazone decreased serum thyroxine (TT4) and free thyroxine (FT4) concentrations using radioimmunoassay and equilibrium dialysis techniques in horses, and, if so, an additional objective was to determine the duration of this decreased concentration once phenylbutazone administration was discontinued. Serum TT4 and FT4 concentrations were determined before and after administration of 4.4 mg/kg of phenylbutazone IV bid for 5 days. Treatment with phenylbutazone caused a significant decrease in TT4 and FT4 concentrations ( P < .05). Serum TT4 concentration significantly decreased after day 4 of treatment and remained significantly below baseline value for 10 days after discontinuing phenylbutazone administration; it returned to a value not different from the baseline value by the 11th day. Serum FT4 concentration significantly decreased after day 4 of treatment and remained significantly below the baseline value for only 1 day after phenylbutazone administration was discontinued; it returned to a value not different from the baseline value by the 3rd day after discontinuation of phenylbutazone. These results indicate that serum TT4 and FT4 should not be used to evaluate thyroid function in horses receiving phenylbutazone. In addition, results should be interpreted cautiously when phenylbutazone has been administered within 2 days (for FT4) or within 10 days (for TT4) of sample collection.  相似文献   

17.
Inhalt: Nach Steuerung der Ovarfunktion beim Rind mit PMSG/PGF und FSH/PGF war 6.5 h nach der PGF-Applikation eine deutliche Abhängigkeit zwischen den Estradiol-17β (E2)- bzw. Testosteron (T)-Konzentrationen in der Follikelflüssigkeit und der Gröβe der Ovarialfollikel zu erkennen. In präovulatorischen Follikeln wurden unabhängig von der gewählten Hormonbehandlung teilweise signifikant höhere (P < 0,05) mittlere E2- und LH-Konzentrationen als in nonovulatorischen Follikeln festgestellt. Follikel mit intakten oder degenerierten Oozyten wiesen keine signifikanten Unterschiede im Steroidgehalt auf. Der Reifungsprozeß der Cumulus-Oozyten-Komplexe bzw. Oozyten war mit charakteristischen Verschiebungen in den intrafollikulären Hormonspiegeln verbunden. Auch die veränderten Verhältnisse der Steroidhormonkonzentrationen in der Follikelflüssigkeit bestätigen die Rolle der Steroide bei der Oozytenreifung.  相似文献   

18.
The anti-inflammatory agent, tepoxalin, was administered to eight healthy 6-month-old female New Zealand white rabbits once daily at an oral dose of 10 mg/kg. Blood samples were obtained immediately before and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 h postadministration on days 1 and 10. Tepoxalin and its active metabolite, RWJ 20142, concentrations were determined in plasma by use of high-performance liquid chromatography with mass spectrometry. C max of the parent compound was reached between 3 and 8 h of drug administration, with a harmonic mean t 1/2 of 3.6 h. Peak tepoxalin plasma concentrations were 207 ± 49 ng/mL. After oral administration, the metabolite RWJ 20142 achieved C max in plasma 2–8 h after administration, with a t 1/2 of 1.9–4.8 h (harmonic mean 2.8 h). Peak plasma concentrations of RWJ 20142 on day 1 were 2551 ± 1034 ng/mL.  相似文献   

19.
A 60-days experiment was conducted to study the optimum gelatinized (G) to non-gelatinized (NG) starch ratio in the diet of Labeo rohita juveniles with respect to digestive and metabolic response and on growth. Two-hundred and thirty-four juveniles (avg. wt 2.53 ± 0.04 g) were randomly distributed in six treatment groups with each of three replicates. Six semipurified diets either containing NG and/or G corn starch viz., T1 (100% NG, 0% G starch), T2 (80% NG, 20% G starch), T3 (60% NG, 40% G starch), T4 (40% NG, 60% G starch), T5 (20% NG, 80% G starch) and T6 (0% NG, 100% G starch) were prepared. The dry matter digestibility and carbohydrate digestibility were highest (p < 0.05) in T6 group and lowest in T3 and T4 groups. The amylase activity in intestine increased as G:NG level increased in the diet. Protease activity in intestine was highest in T6 group and lowest in T1 group. Similar trend was recorded for specific growth rate, protein efficiency ratio and apparent net protein utilization. Liver glycogen, hepatosomatic index and blood glucose level increased linearly with the increasing level of G starch in the experimental diet. The results indicate that higher nutrient digestibility and growth was recorded either at low (20% G starch, T2) or high (100% G starch, T6) G starch fed group. But high G starch fed group (T6) exhibits higher liver glycogen and blood glucose level, which may lead to stress due to long-term feeding. Hence, it is suggested that 20% G and 80% NG starch is optimum for better nutrient digestibility and growth in L. rohita juveniles.  相似文献   

20.
The pharmacokinetics of flunixin were determined after an intravenous dose of 1.1 mg/kg body weight in six camels and 2.2 mg/kg body weight in four camels. The data obtained (mean ±  SEM) for the low and high dose, respectively, were as follows:
  The elimination half-lives ( t ½β) were 3.76 ± 0.24 and 4.08 ± 0.49 h, the steady state volumes of distribution ( V dss) were 320.61 ± 38.53 and 348.84 ± 35.36 mL/kg body weight, total body clearances ( Cl T) were 88.96 ± 6.63 and 84.86 ± 4.95 mL/h/kg body weight and renal clearances ( Cl r) were 0.52 ± 0.09 and 0.62 ± 0.18 mL/h/kg body weight. A hydroxylated metabolite of flunixin was identified by gas chromatography/mass spectrometry (GC/MS) under electron and chemical ionization and its major fragmentation pattern was verified by tandem mass spectrometry (GC/MS/MS) using neutral loss, daughter and parent scan modes. The detection times for flunixin and its hydroxylated metabolite in urine after an intravenous (i.v.) dose of 2.2 mg/kg body weight were 96 and 48 h, respectively.  相似文献   

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