Pathology and Neurotoxicity in Dogs after Repeat Dose Exposure to a Serotonin 5-HT1B Inhibitor

AZD3783, a cationic amphiphilic drug and a potent inhibitor of the 5-hydroxytryptamine (5-HT_1B) 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.     

Can differences in soil community composition after peat meadow restoration lead to different decomposition and mineralization rates?

Reducing decomposition and mineralization of organic matter by increasing groundwater levels is a common approach to reduce plant nutrient availability in many peat meadow restoration projects. The soil community is the main driver of these processes, but how community composition is affected by peat meadow restoration is largely unknown. Furthermore, it is unclear whether restoration induced changes could lead to altered decomposition and mineralization rates. We determined soil community composition in restored peat meadows with different groundwater levels and soil pH. This composition was subsequently used in food web model calculations of C and N mineralization rates to assess whether differences in soil community composition may have contributed to differences in decomposition and mineralization rates observed between these meadows.Community composition of micro-organisms, Collembola and Enchytraeidae differed considerably between meadows and were correlated with differences in groundwater levels and soil pH. Collembolan and enchytraeid species from wet and neutral environments were more abundant at meadows with higher groundwater levels. Lower fungal to bacterial PLFA ratios and higher numbers of protozoa indicated an increased importance of the bacterial part of the food web at meadows with higher groundwater levels. Food web model calculations suggested that the observed changes in community composition would lead to higher rates of C and N mineralization at meadows with high groundwater levels. Results from modeling were consistent with field measurements of C mineralization, but not with measurements of N mineralization.We conclude that understanding changes in soil community composition in response to specific restoration measures may help us to better understand ecosystem responses to wetland restoration schemes, especially regarding soil biogeochemical processes.     

Canopy temperature based system effectively schedules and controls center pivot irrigation of cotton

Cotton is a perennial plant with an indeterminate growth pattern that is typically produced like an annual, but requires proper management to effectively produce high yields and good fiber quality in a thermally limited environment like the northern Texas High Plains. In 2007 and 2008, we investigated the effect of irrigation scheduling/control method and amount on cotton (Gossypium hirsutum L.) yield and water use efficiency. Methods were automatic irrigation scheduling and control of a center pivot system, and manually scheduled irrigation to replenish soil-water to field capacity. Cotton was irrigated with LEPA (low energy, precision application) drag socks in furrow dikes; three blocks were irrigated manually and three were irrigated automatically. Six replicates of the manual and automatic irrigation treatments were included in the randomized block design. Manual irrigations were based on the weekly replenishment of soil-water to field capacity in the top 1.5 m of the soil profile and included a fully irrigated treatment (I₁₀₀), and treatments receiving 67% (I₆₇) and 33% (I₃₃) of the I₁₀₀ amount, plus a non-irrigated treatment (I₀). Automatic irrigations were triggered using a time temperature threshold (TTT) algorithm, which was designated as the I₁₀₀ treatment, and treatments receiving 67%, 33%, and 0% of that amount (I₆₇, I₃₃ and I₀, respectively). In 2007, overall mean lint yields (102.3 and 101.6 g m⁻², manual and automatic, respectively) were not significantly different. Similarly, yields were not significantly different across automatic and manual treatments in the same treatment level, with the exception of the I₆₇ treatment where the manual treatment yields were 11% greater. In 2008, the mean yields were 70% less than those in 2007 for both methods of irrigation (30.3 and 30.9 g m⁻², manual and automatic, respectively) due to harsh climatic conditions at emergence and heavy rainfall and cooler temperatures in the month of August. Yields from the automatically irrigated plots in the I₁₀₀ and I₆₇ treatments, however, were significantly greater than yields from the corresponding manually irrigated plots; though there was no significant difference between yields in the drier treatments (I₃₃ and I₀) plots. These results indicate that the TTT algorithm is a promising method for auto-irrigation scheduling of short season cotton in an arid region. However, further studies are essential to demonstrate consistent positive outcomes.     

采用现代食品加工技术开发蛋白质食物资源

本文分析了现阶段我国人民的食物结构以及食品加工在开发蛋白质食物开源中的地位和作用,并从五个方面进行了论述。     

空气悬架对提高车辆抗倾翻能力的分析

针对近年来商用车侧翻事故的凸现,提出了一种利用空气悬架提高车辆倾翻阀值,减小车辆倾翻危险的方法,编写了控制器,在MATLAB中SIMULINK下建立了七自由度车辆模型,并进行了仿真。仿真结果表明,半主动空气悬架能够有效提高车辆倾翻阀值,提高车辆抗侧翻能力。     

浅谈热水锅炉的安全运行

作者依据20多年的工作实践经验,对热水锅炉安全运行的必要条件进行了较为详细的阐述。     

Toxicity of cultured bullseye puffer fish Sphoeroides annulatus

The toxin content in various life cycle stages of tank-cultivated bullseye puffer (Sphoeroides annulatus) were analyzed by mouse bioassay and ESI-MS spectrometry analysis. The presence of toxin content was determined in extracts of sperm, eggs, embryo, larvae, post-larvae, juvenile, pre-adult, and adult fish, as well as in food items used during the cultivation of the species. Our findings show that only the muscle of juveniles, the viscera of pre-adults, and muscle, liver, and gonad of adult specimens were slightly toxic (<1 mouse unit). Thus, cultivated S. annulatus, as occurs with other cultivated puffer fish species, does not represent a food safety risk to consumers. This is the first report of toxin analysis covering the complete life stages of a puffer fish under controlled conditions.