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AZD3783, a cationic amphiphilic drug and a potent inhibitor of the 5-hydroxytryptamine (5-HT1B) receptor, was explored as a potential treatment for depression. To support clinical trials, repeat dose toxicity studies in rats and dogs were conducted. Here we report toxicity findings in dogs after dosing from 1 to 3 months. In the 1-month study, there were minimal neuronal vacuolation in the brain, a marked increase in liver enzymes accompanied by hepatocellular degeneration/necrosis and phospholipidosis (PLD), and PLD/cholecystitis in the gallbladder of animals dosed at 47 mg/kg/day. In the 3-month study, neurotoxicity resulted in euthanasia of one animal dosed at 30 mg/kg/day after 86 days. Extensive pathologic changes were seen in all animals in retina epithelium (inclusion bodies), brain (neuronal vacuolation, degeneration, or necrosis and nerve fiber degeneration), spinal ganglia (vacuolation, degeneration, or necrosis), as well as sciatic and optic nerves (degeneration). Pigment-laden macrophages were observed in the lung, kidney, liver, gallbladder, bone marrow, gastrointestinal tract, and lymphoid tissues. Also seen were vitrel and retinal hemorrhage in the eyes. A brain concentration and pathology study showed that the concentration of AZD3783 in the brain was approximately 4 times higher than in the plasma after 4 weeks of dosing, however, they were similar in all regions examined, and did not correlate with areas with pathologic findings. Our findings with AZD3783 in dogs have not been reported previously with other CNS compounds that effect through serotonergic pharmacology.  相似文献   
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The objectives were (i) to evaluate the effect of temperament, determined by modified 2‐point chute exit and gait score, on artificial insemination (AI) pregnancy rates in beef heifers following fixed time AI and (ii) to determine the effect of temperament on cortisol, substance‐P, prolactin and progesterone at initiation of synchronization and at the time of AI. Angus beef heifers (n = 967) at eight locations were included in this study. At the initiation of synchronization (Day 0 = initiation of synchronization), all heifers received a body condition score (BCS), and temperament score (0 = calm; slow exit and walk or 1 = excitable; fast exit or jump or trot or run). Blood samples were collected from a sub‐population of heifers (n = 86) at both synchronization initiation and the time of AI to determine the differences in serum progesterone, cortisol, prolactin and substance‐P concentrations between temperament groups. Heifers were synchronized with 5‐day CO‐Synch+ controlled internal drug release (CIDR) protocol and were inseminated at 56 h after CIDR removal. Heifers were examined for pregnancy by ultrasound 70 days after AI to determine AI pregnancy. Controlling for synchronization treatment (p = 0.03), facility design (p = 0.05), and cattle handling facility design by temperament score interaction (p = 0.02), the AI pregnancy differed between heifers with excitable and calm temperament (51.9% vs 60.3%; p = 0.01). The alley‐way with acute bends and turns, and long straight alley‐way had lower AI pregnancy rate than did the semicircular alley‐way (53.5%, 56.3% and 67.0% respectively; p = 0.05). The serum hormone concentrations differed significantly between different types of cattle handling facility (p < 0.05). The cattle handling facility design by temperament group interactions significantly influenced progesterone (p = 0.01), cortisol (p = 0.01), prolactin (p = 0.02) and substance‐P (p = 0.04) both at the initiation of synchronization and at the time of AI. Inter‐ and intra‐rater agreement for temperament scoring were moderate and good (Kappa = 0.596 ± 0.07 and 0.797 ± 0.11) respectively. The predictive value for calm and pregnant to AI was 0.87, and excited and non‐pregnant to AI was 0.76. In conclusion, the modified 2‐point temperament scoring method can be used to identify heifers with excitable temperament. Heifers with excitable temperament had lower AI pregnancy. Further, cattle handling facility design influenced the temperament and AI pregnancy.  相似文献   
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The natural isotopic ratio of 13C/12C (reported as δ C) in plant matter varies predictably among plant types. The isotopic ratio of an animal body reflects the isotopic ratio of the feed metabolized. By selecting inputs to an aquaculture feeding and/or fertilization system such that the components have significantly different δ C values, the relative meta-bolization of each of these inputs by the fish can be measured.

In tank-grown Tilapia aurea (δ C = −17), supplied feed (δ C = −18) provided the carbon incorporated into the fish body even though between feedings the fish consumed large quantities of algae (δ C = −22). In penaeid (δ C = −12) grow-out ponds, δ C analyses indicated that selected components of the feed pellet (average δC = −17; components: corn and sorghum δ C −12, soybeans δ C −25) were metabolized, while the benthic natural foods and other bottom organic matter (δ C = −21) provided little or no input. The value of such information for pond management and nutrition studies is clear.  相似文献   

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Thirty German shepherd bitches were assessed for weekly changes in bodyweight, daily food intake and litter size during pregnancy and lactation. The weekly changes in food intake and bodyweight were divided into two and three phases, respectively. Linear regression equations were used to fit each phase. The bodyweight of the bitches at mating ranged between 17 and 36 kg. The same diet was used for all the bitches throughout the study. Despite the tendency that litter size, birthweight and bodyweight of the puppies at three and six weeks increased with age of the bitch, no significant differences could be found. Significant (P<0·05) bodyweight differences existed at mating between the age groups. High correlations existed between mating weight and weight at 60 days of pregnancy (r2= 0·94] and between mating weight and weaning weight (r2= 0·89) of the litter. It was possible to successfully establish performance criteria for the reproductive German shepherd bitch in a commercial breeding unit, which can be used as a baseline to improve diets and feeding programmes by means of dietary manipulations.  相似文献   
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A study has been conducted on the transformation of Cr(III) and Cr(VI) in simulated natural water conditions. It has been found that these forms are readily interconvertible under natural water conditions. The results of this study indicate that Cr(VI) is reduced by Fe(II), dissolved sulfides, and certain organic compounds with sulfhydryl groups, while Cr(III) is oxidized by a large excess of MnO2 and at a slow rate by Oz under conditions approximating those in natural waters. Based on the results of these studies, water quality standards for Cr should be based on total Cr rather than on Cr(VI), as has been frequently done in the past.  相似文献   
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A greenhouse experiment was conducted with Lolium perenne to determine whether ammonium (NH4+-N) fixation by clay minerals can increase the recovery of nitrogen following application of 15N labelled urea. A silty loam subsoil, Bt horizon from an Alfisol derived from loess, pH (CaCl2) 7.9, was chosen for the experiment. The NH4+-N fixation capacity was altered by varying the distribution of potassium (K) in the upper and lower soil layer. In the K0 treatment (control), the upper soil layer fertilized with urea was not supplied with K, whereas the lower soil layer was fertilized with 300 mg K kg?1 soil. In the K1?, K2? and K3 treatment the upper soil was supplied with 100-, 200- and 300 mg K kg?1 soil, respectively. The soil in the lower layer of the K3 treatment was not supplied with K. The recovery of 15N from applied urea (15N uptake of Lolium perenne plus residual soil 15Nt) was 86.1% in the K0 treatment and 75.2%, 69.1% and 69.6% in K1-, K2- and K3 treatments, respectively, showing that 15N losses were smallest in the K0 treatment. Two weeks after applying 15N labelled urea the amounts of nonexchangeable 15NH4+-N in the upper soil layer were significantly higher in the K0 treatment than in the treatments with K application. Apparently, NH4+-N fixation by clay minerals can reduce NH3 volatilization after urea fertilization, if the amount of exchangeable K is low.  相似文献   
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