Effect of disposition on the relative delayed neurotoxicity potency among leptophos analogs

The oxons of leptophos, its desbromo analog, and its ethoxy analog all inhibit hen brain neurotoxic esterase (NTE) to a similar degree in vitro, but have large differences in minimum effective oral doses for organophosphorus-induced delayed neurotoxicity. The potencies of leptophos and ethoxyleptophos are increased 10-fold when administered to hens intravenously (iv), but the potency of desbromoleptophos is nearly the same whether administered iv or po. Leptophos distributes nearly five times more rapidly from the central compartment than does desbromoleptophos, and its attenuated oral potency may be due to slower net absorption and/or dilution by compartments other than nervous tissue. Intravenously administered phenylphosphonothionates are excreted rapidly into the gastrointestinal tract and a large proportion of the dose is eliminated in the first 48 hr. Indirect evidence indicates that ethoxyleptophos is more rapidly degraded and ethoxyleptophos-inhibited NTE recovers more rapidly than does NTE inhibited by leptophos or desbromomleptophos. It is proposed that differential aging of ethoxyleptophos chiral isomers as well as pharmacokinetic factors may contribute to the apparently anomalous behavior of these three analogs.     

Glycosylated Hemoglobin Concentration for Assessment of Glycemic Control in Diabetic Cats

Blood glycosylated hemoglobin (GHb) concentration was quantified in 84 healthy cats, 9 cats with stress-induced hyperglycemia, 37 cats with newly diagnosed diabetes mellitus, and 122 diabetic cats treated with insulin or glipizide. Diabetic control was classified as good or poor in insulin-treated or glipizide-treated cats based on review of history, physical examination findings, changes in body weight, and measurement of blood glucose concentrations. Blood GHb concentration was determined using an affinity chromatography assay. Mean blood GHb concentration was similar for healthy normoglycemic cats and cats with transient, stress-induced hyperglycemia, but was significantly (P < .001) higher in untreated diabetic cats when compared with healthy normoglycemic cats. Mean blood GHb concentration was significantly (P < .001) higher in 84 cats with poorly controlled diabetes mellitus when compared with 38 cats in which the disease was well controlled. Mean blood GHb concentration decreased significantly (P < .01) in 6 cats with untreated diabetes mellitus after insulin and dietary treatment. A similar significant (P < .01) decrease in mean blood GHb concentration occurred in 7 cats with poorly controlled diabetes mellitus after diabetic control was improved by an increase in insulin dosage from 1.1 ± 0.9 to 1.4 ± 0.6 U/kg/ 24 h and by feeding a diet containing increased fiber content and in 6 cats with transient diabetes mellitus 8.2 ± 0.6 weeks after discontinuing insulin treatment. There was a significant (P< .01) stress-induced increase in mean fasting blood glucose concentration and mean blood glucose concentration for 12 hours after administration of insulin or glipizide but no change in mean blood GHb concentration in 5 docile diabetic cats 12.2 ± 0.4 weeks after the cats became fractious as a result of frequent hospitalizations and blood samplings. Results of this study suggest that evaluation of blood GHb concentration may be a clinically useful tool for monitoring glycemic control of diabetes in cats.     

Risk factors associated with mortalities attributed to infectious salmon anaemia virus in New Brunswick, Canada

Outbreaks of unexplained mortalities attributed to infectious salmon anaemia (ISA) were examined in the 1996 year class of Atlantic salmon in three regions of New Brunswick, Canada. A total of 218 net pens at 14 sites deemed to have been exposed to ISA virus (ISAV) were surveyed for mortality records and management, environmental and host characteristics. Based on definitions of mortality patterns, clinical ISA disease outbreaks occurred in 106 net pens. There were eight sites in which >50% of net pens experienced ISA outbreaks during the study period. Factors related to their potential role in transmission of virus to new sites or new net pens at the same site were identified as sea lice vectors, divers visiting multiple sites, sites belonging to companies with more than one site, exposure to other year classes at the site, and proximity to other infected net pens. Host resistance factors associated with greater risk of outbreaks were identified as larger groupings, general health following smolt transfer, stressful husbandry procedures during growout, and health or productivity during colder water periods. Despite very close proximity between sites, modification of these management factors would probably influence the severity of mortalities caused by ISAV.     

Modification of Marine Natural Product Ningalin B and SAR Study Lead to Potent P-Glycoprotein Inhibitors

In this study, new marine ningalin B analogues containing a piperazine or a benzoloxy group at ring C have been synthesized and evaluated on their P-gp modulating activity in human breast cancer and leukemia cell lines. Their structure-activity relationship was preliminarily studied. Compounds 19 and 20 are potent P-gp inhibitors. These two synthetic analogues of permethyl ningalin B may be potentially used as effective modulators of P-gp-mediated drug resistance in cancer cells.     

植物根系对土壤水力参数影响的定量研究综述

植物根系是土壤结构以及土壤水力参数变化的重要影响要素。目前不仅缺乏定量描述“根-孔隙-土壤水力参数”相互作用的研究方法,在更大尺度上根系作用的客观表达也尚不明确,由此导致降雨入渗、径流和蒸发等流域水文过程的精细刻画与模拟预测具有很大的不确定性。基于文献检索,本文对国内外相关研究进行了回顾与梳理,量化了植物根系对土壤水力参数的改变和影响,并提出其与植被、土壤类型的响应方式,总结了植物根系动态性生长下的土壤水力参数定量表述及其预测模型进展。同时分析了在定量研究根-土复合系统中存在的问题及未来研究的发展方向,指出目前根系影响土壤水力参数的研究主要集中在小尺度控制实验方面,忽略了大尺度下土壤空间异质性及外部环境因素的干扰,强调大尺度根系作用和根系参数纳入土壤结构的重要性和实际意义,进一步与水文模型的深度耦合逐渐成为未来研究的热点。     

Evaluation of L-selectin expression and assessment of protein tyrosine phosphorylation in bovine polymorphonuclear neutrophil leukocytes around parturition

Impaired polymorphonuclear neutrophil leukocyte (PMN) function around parturition has been associated with increased clinical mastitis in dairy cows. Rolling and attachment of PMN to the endothelium is the first step in the recruitment process and is accomplished by interaction between L-selectin on PMN and its ligand on endothelial cells. Furthermore, tyrosine phosphorylation is involved in the initiation of many PMN functions. The objective of this work was to determine changes in expression of L-selectin and tyrosine phosphorylation in the perinatal period. Eight clinically healthy Holstein cows were used as PMN donors at d-21, -14, -7,0 (calving), +1, +2, +7, +14, +28. Evaluation of L-selectin expression was carried out on activated and resting PMN. Anti-bovine L-selectin monoclonal antibody (MAB) and flow cytometric analysis were used to measure the percentage of PMN fluorescing and receptor expression (log mean fluorescent channel, LMFC). Activated and resting PMN showed similar trends in % PMN fluorescence and LM FC. The percentage of PMN fluorescing tended to decrease at parturition, followed by a significant increase at d +14 and +28 (P < 0.02). For LMFC a decrease was observed on d +1 followed by an increase through d +28 (P < 0.01). Protein tyrosine phosphorylation of lysates prepared from PMN isolated throughout the study was detected by electrophoresis and western blotting using anti-phosphotyrosine MAB. Several protein bands were tyrosine phosphorylated. Two of these bands (42-44 kDa and 90 kDa) varied in intensity over time. The intensity of the 42-44 kDa band gradually increased from d -7, peaked at d +7 (P < 0.03), and steadily decreased to d +28 (P < 0.02). Antibody to activated mitogen protein kinase reacted with the 42-44 kDa band. Reduced PMN function during the periparturient period could be related to reduced L-selectin adhesion molecules on the cell surface, and to modulation in the phosphorylation of functionally important molecules.     

Postharvest changes in pigment concentrations in ‘Fuji’ apples with ‘Fuji’ stain

’Fuji’ apples (Malus domestica Borkh cv. ‘Fuji’) sometimes develop a discolouration in the peel during cold storage, typically in the periphery of sunburned peel. We refer to this particular postharvest disorder as ‘Fuji’ stain as we have not observed it in any cultivar other than ‘Fuji’ and the discolouration looks like a stain on the peel. Because peel discolouration occurs, peel pigments are thought to be involved. Hence the concentrations of anthocyanins, epicatechin, quercetin glycosides, chlorogenic acid, chlorophylls, and carotenoids in peel disks taken from areas exhibiting ‘Fuji’ stain were compared to concentrations observed in peel disks not exhibiting ‘Fuji’ stain. In 2005, peel from sunburned apples exhibiting ‘Fuji’ stain was compared to peel from three areas of sunburned apples not exhibiting stain [i.e. sunburned peel, the area around the sunburned peel (halo), and the area around the halo (OH)]. Additionally, stained peel was compared to the sun-exposed side of non-stained non-sunburned apples (NSNB). The second year, 2006, we compared stained peel to NSNB peel and the area outside the stained area (OS) on those fruit with stain. The concentrations of idaein, epicatechin, and quercetin glycosides were consistently low in the stained peel both years. This is in contrast to our earlier studies in which sunburned ‘Fuji’ apples had high concentrations of quercetin glycosides and epicatechin and low concentrations of idaein, and non-sunburned apples had low concentrations of quercetin glycosides and epicatechin and high concentrations of idaein. The consistent and unique characteristic of stained peel reported here indicates an association of these compounds with the incidence of stain. In 2005, chlorogenic acid concentrations in the stain peel were lower than other peel types, but in 2006 they were higher. Differences in chlorophyll and carotenoid concentrations were observed among many of the peel types. However, there is not a clear association between stain development and changes in chlorophyll and carotenoid concentrations due to significant differences not being observed in both years. While our research provides insight into pigment changes associated with ‘Fuji’ stain formation, more work is needed to help clarify the inconsistencies observed between the 2 years.