Aspirin-Interleukin-3 Interrelationships in Patients With Anti-Phospholipid Syndrome

PROBLEM: Previously we reported on the generation of experimental anti-phospholipid syndrome (APS) in mice. These models were employed to evaluate the efficacy of various novel therapeutic modalities including interleukin-3 (IL-3) and low dose aspirin. The efficacy of the latter was found to be interrelated. Low dose aspirin is capable of inhibiting the activity of the enzyme cyclooxygenase which is responsible for the metabolism of arachidonic acid towards the production of prostaglandins. This shifts the metabolism of arachidonic acid to the other pathway and leads to an overproduction of leukotrienes. The leukotrienes act as stimulators of IL-3 production, a positive cytokine in pregnancy which enhances placental and fetal development. In the current study we evaluated the IL-3 levels in pregnant women with APS and expanded our knowledge on the interrelationships between aspirin, arachidonic acid metabolites and IL-3 in the human system. METHODS: IL-3 levels were recorded in the serum of pregnant women with APS and compared to a control pregnant group. In addition peripheral blood mononuclear cells from healthy subjects were incubated with different concentrations of aspirin or with arachidonic acid metabolites (Leukotriene B4, C4 or PGE₂), and IL-3 production in the culture fluids was evaluated. RESULTS: Serum level of IL-3 in pregnant patients with primary APS, APS secondary to SLE and SLE was lower in comparison to the control group. The in vitro studies revealed that only low dose aspirin (10 mg/μl) stimulated IL-3 production while higher doses of the drug failed to induce the cytokine generation. Leukotriene B4 and C4 were stimulatory whereas PGE₂ acted as inhibitor of IL-3 production. CONCLUSIONS: The serum level of IL-3 is decreased to pregnant women with primary or secondary APS. Low dose aspirin is capable of stimulating EL-3 production in vitro most probably through an elevation of leukotriene production, which may explain its beneficial activity in preventing the manifestations of APS.     

The relationship between exposure duration,carboxyhemoglobin, blood glucose,pyruvate and lactate and the severity of intoxication in 39 cases of acute carbon monoxide poisoning in man

The relationship between exposure duration, COHb, blood glucose, pyruvate and lactate and the severity of intoxication was investigated in a group of 39 cases of acute CO poisoning treated in the Clinical Toxicology Center in ód, Poland.On the basis of clinical criteria the patients were classified into cases of mild, moderate, severe and very severe CO poisoning. COHb and carbohydrate metabolites were estimated in venous blood taken immediately after admission of the patient to hospital prior to treatment.The severity of intoxication did not correlate with blood COHb; variation in exposure duration seems to be responsible for this phenomenon. Severe and very severe poisonings were associated with longer exposures and were accompanied by a markedly higher blood lactate level, compared to mild and moderate cases. Blood pyruvate depended less than lactate on the severity of intoxication. Blood glucose depended neither on exposure duration nor on the severity of intoxication.Among the carbohydrate metabolic parameters studied, blood lactate determination can be helpful in the evaluation of the severity of CO poisoning in man.     

Determination of isotretinoin or etretinate and their major metabolites in human blood by reversed-phase high-performance liquid chromatography

A method is described for the quantitative analysis of isotretinoin and its 4-oxo metabolite, or of etretinate and its principal metabolites, in human blood in the range 10-2000 ng/ml. Following a simple one-step extraction, the compounds are determined by reversed-phase high-performance liquid chromatography (HPLC) with gradient elution and detection at 365 nm. This highly specific method separates the cis and trans isomers of the parent compounds and their metabolites. Examples are given of the application of this method to clinical studies of these two therapeutically important retinoids.     

Determination of free fractions of tricyclic antidepressants

Summary The plasma protein binding of amitriptyline, imipramine, clomipramine, and their primary demethylated metabolites were studied by means of a method combining dialysis and gas chromatography. Equilibrium in dialysis of serum containing amitriptyline and its metabolite nortriptyline was attained in about 0.5 h with the drug dissolved in the serum compartment, and in about 2 h with the drug passing from the buffer to the serum compartment.The calculation of free fractions was influenced by variations with dialysis time in the volumes of serum and buffer. Increase of pH in serum increased the protein binding of the weakly basic drugs studied, and made the Donnan distribution effects more pronounced. At pH 7.4, the Donnan effect was negligible.Binding parameters for the 6 tricyclic antidepressant substances studied were estimated for the binding to ₁-acid glycoprotein and for total binding in serum. For ₁-acid glycoprotein, the k-values ranged from 1·10⁵ to 8·10⁵ M^–1, and for pooled serum from 0.4·10⁵ to 8·10⁵ M^–1. The determined number of binding sites on the ₁-acid glycoprotein was, on average 0.87 for the 6 substances. In serum, the binding capacity was 2–14 times the concentration of ₁-acid glycoprotein.     

Increased metabolism to dihydrodigoxin after intake of a microencapsulated formulation of digoxin

Summary A capsule preparation containing small, enteric-coated granules of digoxin was developed to prevent acid hydrolysis of the drug in the stomach and to diminish the variation in plasma glycoside concentration during the intervals between doses. The absorption and metabolism of tritiated digoxin after a single oral loading dose of this formulation (Formulation C) were compared to those after ingestion of a digoxin solution (Formulation S) by 8 healthy men. Drug concentrations were measured by radioimmunoassay (RIA) and liquid chromatography (LC). The percentage of the digoxin dose excreted in the urine during 72 h, as measured by RIA, was significantly lower after the capsule (20.5±2.0% vs 36.2±3.0% after S, mean±SEM) but total urinary radioactivity after the two treatments was similar (C 35.3±5.2 and S 41.2±2.6%; p>0.05). The discrepancy was mainly due to significantly greater excretion of dihydrodigoxin after the capsule ( 12.8%, range 0–28.6% of the dose) than after the digoxin solution ( 5.4%, range 0–14.5%). Dihydrodigoxin was not measured by the RIA. The recovery of hydrolysis metabolites (LC) was greater during the first 24 h after S (2.3±0.6% vs 0.9±0.3% after C; p<0.05). The peak plasma concentration of digoxin (RIA) was significantly reduced and delayed after intake of C (2.5±0.4 nmol/l at 3.8±0.3 h vs. 8.3±0.8 nmol/l at 0.9±0.1 h after S), and so was the shortening of electromechanical systole at 1.5 h, 2.5 h, and 3 h. Thus, the enteric-coated digoxin preparation delayed the absorption and reduced the hydrolysis of the glycoside, but it also carried the drawback of reducing digoxin availability, mainly because of increased metabolism to dihydrodigoxin.     

一种复合微生物菌肥对穿心莲生长、品质及土壤性质的影响

目的：研究一种微生物复合菌肥对穿心莲生长、品质及土壤性质的影响,旨在为穿心莲栽培生产中微生物复合菌肥的应用提供依据。方法：通过盆栽的共5个处理试验,CK（不施肥）组、A处理（施化肥）组、B处理（施微生物菌肥,施用量为2.5 g·kg-1土）组、C处理（施微生物菌肥,施用量为7.5 g·kg-1土）组、D处理（施微生物菌肥,施用量为12.5 g·kg-1土）组,研究一种复合微生物菌肥对穿心莲的农艺性状、有效成分含量及根际土壤细菌、放线菌、真菌的数量和土壤理化性质的影响。结果：施加一定量的复合微生物菌肥,穿心莲的株高、叶片数、叶面积、地上部、地下部鲜重较CK组和A处理组显著升高,不同生长期有差异。复合微生物菌肥对穿心莲内酯、脱水穿心莲内酯、新穿心莲内酯及14-去氧穿心莲内酯含量影响有差异,与CK组、A处理组比较,C处理组的穿心莲内酯分别明显升高26.13%、13.23%(P<0.05);新穿心莲内酯的含量随微生物菌肥施加量的增加而增加,在D处理组下的效应最显著,与CK组、A处理组比较,分别明显升高9.06%、50.33%(P<0.05);B处理组的14-去氧穿心莲内酯较A处理组...     

微酸性电解水实验室微生物杀灭效果研究

 目的 研究某微酸性电解水实验室微生物杀灭效果。方法 选取某次氯酸水发生器现制微酸性电解水,测定不同有效氯含量、不同作用时间其对细菌繁殖体、芽孢以及真菌的杀灭效果。结果 该微酸性电解水有效氯含量为34.3~118 mg/L,有机干扰物牛血清白蛋白浓度为3.0%和0.3%时,分别作用1.0、3.0、5.0、10.0 min,对金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌的平均杀灭对数值均>5.00,对白假丝酵母菌的平均杀灭对数值均>4.00;有效氯含量为101~118 mg/L,牛血清白蛋白浓度为0.3%时,分别作用5.0、10.0、30.0 min,对枯草杆菌黑色变种芽孢的平均杀灭对数值均>5.00。结论 在特定实验条件下,该微酸性电解水对细菌的繁殖体、芽孢以及真菌均达到消毒剂消毒合格标准。     

应用综合干预措施提高临床微生物标本送检质量

 目的 应用综合干预措施,提高临床微生物标本送检质量。方法 调查2018年9月—2020年8月某院治疗性使用抗菌药物的住院患者,2019年9月开始实施综合干预措施。综合干预措施包括签订责任书、工作质量考核与反馈、知识培训、信息系统控制等,比较干预前（2018年9月—2019年8月）与干预后（2019年9月—2020年8月）住院患者抗菌药物治疗前微生物标本、无菌性标本、呼吸道标本及血培养标本送检情况。结果 共调查治疗性使用抗菌药物的住院患者40 335例,干预前21 441例,干预后18 894例。干预后抗菌药物、限制级抗菌药物、特殊级抗菌药物治疗前微生物标本送检率分别为65.20%、67.36%、99.02%,高于干预前的63.64%、64.68%、91.27%,差异均有统计学意义（均P<0.05）。无菌性标本送检率由干预前的13.81%提高至干预后的15.85%,呼吸道标本送检率由干预前的37.63%下降至干预后的35.68%,差异均有统计学意义（均P<0.001）。无菌性标本占比由干预前的30.43%提高至干预后的34.84%,呼吸道标本占比由干预前的45.74%下降至干预后的40.09%。两套及以上血培养标本占比由干预前的18.63%上升至干预后的21.95%,差异具有统计学意义（P<0.001）。结论 应用综合干预措施可同时提高临床微生物标本送检率与送检质量。     

创伤性脊髓损伤患者血清和尿液的代谢组学分析

背景:创伤性脊髓损伤在临床上主要依赖于量表评估与影像学检查,但对于损伤程度的预后评估具有一定局限性,利用代谢组学技术进行生物标志物筛选,对于估计病变范围、损伤与恢复程度以及开发新疗法具有重要意义。目的:使用代谢组学技术来表征创伤性脊髓损伤患者的代谢特征,探寻潜在的生物标志物及失调的代谢途径。方法:收集20例创伤性脊髓损伤患者(观察组)和10例健康受试者(对照组)的血清和尿液样本,进行代谢物分析,然后利用多元变量统计分析进行数据处理,筛选差异代谢物。通过MetaboAnalyst软件进行代谢通路富集,应用logistic回归构建生物标志物组合模型,并分析其与美国脊髓损伤协会(ASIA)分级的关系。结果与结论:两组受试者的血清和尿液中分别检测出160种和73种具有显著差异的代谢物。通路富集分析显示,创伤性脊髓损伤后脂质代谢出现明显的紊乱,包括鞘脂类、亚油酸、α-亚麻酸和花生四烯酸代谢以及糖基磷脂酰肌醇生物合成。识别出他索沙坦和葫芦素糖苷这组生物标志物,并且二者构成的代谢物组合在血清和尿液中的水平与ASIA分级存在相关性。由此可见,代谢组学技术为进一步理解创伤性脊髓损伤病理机制、筛选治疗靶点提供帮助。识别出的代谢生物标志物组合可能为评估创伤性脊髓损伤的严重程度提供参考。     

非靶向代谢组学揭示天葵不同部位差异代谢物及其主要代谢途径

目的:利用非靶向代谢组学挖掘天葵非药用部位潜在的药用价值。方法:以天葵茎、叶、花为材料,利用超高效液相色谱-质谱法对其进行非靶向代谢组学分析。结果:天葵茎、叶、花中共鉴定出16大类101个差异代谢物(DAMs),其中包含羧酸及其衍生物、有机含氧化合物、脂质、苯及其取代衍生物、生物碱、黄酮类、萜类、苯丙素类、酚酸类、核苷酸、有机盐、内酯、有机酸、内源性植物激素、氨基酸和13个其他物质。通过聚类和京都基因与基因组百科全书(KEGG)分析发现,天葵不同部位的DAMs代谢模式存在一定的差异;其主要代谢途径为苯丙氨酸代谢途径、ABC转运途径、氨酰-tRNA合成途径及苯丙氨酸、酪氨酸和色氨酸生物合成途径。结论:通过天葵不同部位间DAMs的鉴定及其生物合成途径的分析,确定天葵茎、叶、花富含多种具有药用功效的代谢活性物质,可为天葵茎、叶、花的资源开发利用提供参考。