Epipolythiodiketopiperazines from the Marine Derived Fungus Dichotomomyces cejpii with NF-κB Inhibitory Potential

The Ascomycota Dichotomomyces cejpii was isolated from the marine sponge Callyspongia cf. C. flammea. A new gliotoxin derivative, 6-acetylmonodethiogliotoxin (1) was obtained from fungal extracts. Compounds 2 and 3, methylthio-gliotoxin derivatives were formerly only known as semi-synthetic compounds and are here described as natural products. Additionally the polyketide heveadride (4) was isolated. Compounds 1, 2 and 4 dose-dependently down-regulated TNFα-induced NF-κB activity in human chronic myeloid leukemia cells with IC_50s of 38.5 ± 1.2 µM, 65.7 ± 2.0 µM and 82.7 ± 11.3 µM, respectively. The molecular mechanism was studied with the most potent compound 1 and results indicate downstream inhibitory effects targeting binding of NF-κB to DNA. Compound 1 thus demonstrates potential of epimonothiodiketopiperazine-derived compounds for the development of NF-κB inhibitors.     

Carotenoids from Marine Microalgae: A Valuable Natural Source for the Prevention of Chronic Diseases

Epidemiological studies have shown a relation between antioxidants and the prevention of several chronic diseases. Microalgae are a potential novel source of bioactive molecules, including a wide range of different carotenoids that can be used as nutraceuticals, food supplements and novel food products. The objective of this review is (i) to update the research that has been carried out on the most known carotenoids produced by marine microalgae, including reporting on their high potentialities to produce other less known important compounds; (ii) to compile the work that has been done in order to establish some relationship between carotenoids and oxidative protection and treatment; (iii) to summarize the association of oxidative stress and the various reactive species including free radicals with several human diseases; and (iv) to provide evidence of the potential of carotenoids from marine microalgae to be used as therapeutics to treat or prevent these oxidative stress-related diseases.     

长期氧疗对慢性阻塞性肺病患者的疗效分析

目的：探讨长期氧疗(LTOT)对慢性阻塞性肺病(COPD)患者的疗效。方法：对46例COPD稳定期患者进行3a的LTOT、于LTOT前及LTOT后观察患者住院次数、呼吸困难改善情况、动脉血气分析及血浆白蛋白的变化情况。结果：氧疗后1、2、3a与氧疗前基础值比较,患者住院次数减少,呼吸困难等临床症状显著减轻,低氧血症改善,营养状况好转。结论：合理使用LTOT对COPD患者有良好的治疗作用．可提高患者生活质量。     

Induction of oxidative stress and lipid peroxidation in rats chronically exposed to cypermethrin through dermal application

Present study was undertaken to study the effect of cypermethrin on oxidative stress after chronic dermal application. The insecticide was applied dermally at 50 mg/kg body weight in different groups of Wistar rats of either sex weighing 150~200 g. Significant (p < 0.05) increase in catalase activity was observed after 30 days of exposure. However, the superoxide dismutase activity declined significantly after 60 days of exposure. The activity of glutathione peroxidase and blood glutathione levels declined significantly (p < 0.05) after 30 days of cypermethrin dermal application. However, the activity of glutathione S-transferase increased significantly (p < 0.05) in all groups after 60 days of dermal exposure. Significant increase in lipid peroxidation was observed from 30 days onwards and reached a peak after 120 days of application.     

Flow cytometric patterns in blood from dogs with non-neoplastic and neoplastic hematologic diseases using double labeling for CD18 and CD45

BACKGROUND: In dogs, flow cytometry is used in the phenotyping of immunologic cells and in the diagnosis of hemic neoplasia. However, the paucity of specific antibodies for myeloid cells and B lymphocytes and of labeled antibodies for multicolor techniques limits the ability to detect all leukocyte subpopulations. This is especially true for neoplastic and precursor cells. CD18 and CD45 are expressed on all leukocytes and are involved in cell activation, and together could be useful in helping determine cell lineage. OBJECTIVES: The purpose of this study was to double label canine blood for CD18 and CD45 and to use the differential expression of antigens to identify leukocyte populations in dogs with non-neoplastic and neoplastic hematologic diseases. METHODS: A template was developed using blood samples from 10 clinically healthy dogs and a back-gating technique. Differential leukocyte counts obtained with the template were compared with those obtained by manual and automated methods on blood samples from 17 additional healthy dogs. Blood samples obtained from 9 dogs with non-neoplastic (reactive) hematologic diseases and 27 dogs with hemic neoplasia were double stained for CD18 and CD45 using mouse anticanine CD18 monoclonal antibody (mAb) plus phycoerythrin-conjugated rat anticanine CD45 mAb and fluorescein isothiocyanate-conjugated rabbit antimouse IgG. Hemic neoplasms were diagnosed by cell morphology, and immunophenotypic and cytochemical markers. RESULTS: With the double label, neutrophils, eosinophils, monocytes, and T- and B-lymphocytes were identified. In reactive disorders, a population of activated neutrophils with high CD45 and CD18 expression was detected. In hemic neoplasia, cell lineage was easily determined, even in acute leukemia. CONCLUSIONS: Double labeling for CD18/CD45 may be useful as a screening method to evaluate hematologic diseases and help determine cell lineage, and to aid in the selection of a panel of antibodies that would be useful for further analysis.     

高毒有机磷农药慢性危害评估方法研究

为探索高毒有机磷农药残留对人群慢性危害的评估方法,本文以江苏省甲胺磷、甲拌磷、对硫磷、甲基对硫磷以及氧乐果在蔬菜中残留的实测数据和文献中相关参数为基础资料,采用饮食暴露模型(DEEM)估算江苏省人群对蔬菜中这5种有机磷农药残留的暴露水平,分别采用参考剂量百分比、暴露边缘以及日允许摄入量百分比3种评估方法从不同角度对其慢性危害进行分析。危害分析结果表明:江苏省人群对蔬菜中这5种有机磷农药的暴露水平目前仍属于安全范围。3种评估方法同时对慢性危害进行评估,可以避免遗漏高风险农药,同时量化农药的慢性危害。     

DNA methylation and targeted sequencing of methyltransferases family genes in canine acute myeloid leukaemia,modelling human myeloid leukaemia

Tumours shows aberrant DNA methylation patterns, being hypermethylated or hypomethylated compared with normal tissues. In human acute myeloid leukaemia (hAML) mutations in DNA methyltransferase (DNMT3A) are associated to a more aggressive tumour behaviour. As AML is lethal in dogs, we defined global DNA methylation content, and screened the C‐terminal domain of DNMT3 family of genes for sequence variants in 39 canine acute myeloid leukaemia (cAML) cases. A heterogeneous pattern of DNA methylation was found among cAML samples, with subsets of cases being hypermethylated or hypomethylated compared with healthy controls; four recurrent single nucleotide variations (SNVs) were found in DNMT3L gene. Although SNVs were not directly correlated to whole genome DNA methylation levels, all hypomethylated cAML cases were homozygous for the deleterious mutation at p.Arg222Trp. This study contributes to understand genetic modifications of cAML, leading up to studies that will elucidate the role of methylome alterations in the pathogenesis of AML in dogs.     

连续肌注恩诺沙星对中华草龟的急性和慢性毒理研究

为研究恩诺沙星对人工养殖中华草龟Chinemys reevesiis的药物毒性影响,在急性毒性试验中,将60只体质量约20 g的中华草龟随机分为6组,分别注射剂量为649.9、484.1、360.5、268.5、200.0、0(对照)mg/kg(体质量)的恩诺沙星,在慢性毒性试验中,将16只体质量约为100 g的中华草龟随机分为4组,分别注射剂量为0(对照)、10、30、50 mg/kg(体质量)的恩诺沙星,连续注射30 d,停药30 d,并在第0、2、13、28、40、50、60 d各抽取0.4 m L血液进行生化检测。结果表明:急性毒性试验中,观察两周后用Bliss法计算出半数致死浓度(LD50)为434.45 mg/kg,对死亡龟进行组织学检查显示,龟肝组织的肝细胞索结构混乱,有较严重淤血,大量嗜酸性粒细胞浸润,胃肠壁有水肿;慢性毒性试验中,注射过程中高剂量组(50 mg/kg)3只龟死亡,中剂量组(30 mg/kg)1只龟死亡,龟血清谷草转氨酶(AST)活性随时间呈先上升后下降的趋势,中剂量组显著高于低剂量组(10 mg/kg)和对照组(P0.05),在停止注射后,中、高剂量组总胆红素(T-bil)含量均迅速上升,剖检和组织学检查可见高剂量组肝脏密度减小,肝组织出现大小不一的空泡变性,肝小叶和肝细胞索无法辨识,肺组织结构混乱,胃肠道内有黄色黏稠液体,胃肠壁变薄、水肿,而肾组织无严重病变,注射部位肌肉出现较严重的水肿和炎症。研究表明,连续肌注恩诺沙星对中华草龟具有明显的肝毒性,且对肺、胃、肠道和肌肉组织也有一定的毒性,无肾毒性。     

复方柴金解郁片对慢性应激抑郁大鼠HPA轴及海马单胺神经递质的影响

目的 研究复方柴金解郁片对慢性应激抑郁模型大鼠HPA轴及海马单胺神经递质的影响,探讨其可能的抗抑郁机制。方法 将SD大鼠随机分为6组：对照组、模型组、氟西汀组（5.4 mg/kg）、复方柴金解郁片高、中、低剂量组（2.74、1.37、0.68 g/kg）,采用慢性不可预见性温和应激建立抑郁模型,于造模同时给药,连续28 d。采用蔗糖偏好实验和旷场测试检测大鼠的抑郁样行为,Morris水迷宫检测大鼠的学习记忆能力,HE染色观察大鼠海马病理结果变化,ELISA法检测大鼠血浆促肾上腺皮质激素释放激素（CRH）、促肾上腺皮质激素（ACTH）、皮质酮（CORT）,以及海马5-羟色胺（5-HT）、5-羟吲哚乙酸（5-HIAA）、去甲肾上腺素（NA）、多巴胺（DA）的含量。结果 与抑郁模型组比较,复方柴金解郁片组大鼠蔗糖偏嗜度及活动次数均显著提高,学习记忆能力提升,海马病理损伤情况得到缓解,血浆CRH、ACTH、CORT含量下降,海马组织内5-HT、NA、DA含量上升,5-HIAA含量下降（P<0.05）。结论 复方柴金解郁片能显著改善模型大鼠情绪和学习记忆功能、缓解海马组织损伤,其作用可能与抑制HPA轴亢进、增加脑内单胺递质含量有关。     

大蒜素治疗细菌感染所致呼吸机相关性肺炎的临床研究

目的 评估大蒜素治疗细菌感染所致呼吸机相关性肺炎危重患者的临床疗效。方法 采用前瞻性随机对照研究方法,选取2011年01月-2014年12月收入重症监护病房且符合呼吸机相关性肺炎诊断标准的92例患者（均为细菌感染所致）,按照随机数字表法将其分为治疗组42例及对照组50例。对照组在常规治疗基础上加用抗生素治疗,治疗组在对照组基础上加用大蒜素治疗,疗程14 d。分析两组患者的病原菌分布情况,比较两组患者机械通气时间、抗生素治疗时间、住ICU时间及14 d病死率;并观察记录大蒜素使用过程中安全性及不良反应发生率。结果 细菌感染所致呼吸机相关性肺炎患者的常见病原菌为鲍曼不动杆菌（35.2%）、金黄色葡萄球菌（17.1%）、铜绿假单胞菌（13.3%）、肺炎链球菌（13.3%）及肺炎克雷伯菌（8.6%）。治疗组机械通气时间略短于对照组（P>0.05）,抗生素使用时间及住ICU时间显著短于对照组（P<0.01）。两组患者治疗后14 d病死率无统计学差异（P>0.05）。结论 细菌感染所致呼吸机相关性肺炎患者在常规抗感染治疗基础上加用大蒜素治疗,能显著缩短抗生素使用时间,且有缩短患者机械通气时间及住ICU时间,临床不良反应发生率低,可以安全使用。