纳豆激酶的发酵工艺及其制剂学研究

目的研究纳豆激酶的发酵及其胶囊的制备工艺。方法考察纳豆激酶发酵提取液的热稳定性,并对纳豆激酶的制剂工艺进行研究。结果通过简单的制备工艺所制得的纳豆激酶胶囊,装量差异、含量均匀度、崩解时限均符合《中国药典》的要求。结论将纳豆激酶转化成可供临床应用的制剂具有重要意义。     

纳豆激酶对实验动物溶栓作用的研究

目的观察纳豆激酶在体内溶解血栓的作用。方法利用30%FeCl3制造大鼠颈动脉血栓模型,随机分为5组,包括血栓对照组,低剂量纳豆激酶组,高剂量纳豆激酶组,蚓激酶对照组和生理盐水对照组。利用花生油喂食的方法构建高脂血症动物模型,分成4组进行试验,包括普通饲料对照组,添加花生油对照组,同时添加低剂量纳豆激酶和同时添加高剂量纳豆激酶组。结果血栓复制40 min后,纳豆激酶组与单纯血栓组相比,股动脉血压显著下降。此外,纳豆激酶组与单纯血栓组比较,经纳豆激酶处理的动物其血栓的湿质量、干质量降低。在高脂血症动物模型中,添加纳豆激酶组表现出总胆固醇(TC)和高密度脂蛋白胆固醇(HDL-C)明显降低,而且这种趋势随着纳豆激酶量的增高更加显著。结论纳豆激酶在体内具有明显的溶栓效果,并且有一定的预防和降低血脂的作用。     

纳豆激酶药理作用研究进展

纳豆激酶具有高效抗血栓作用,具有安全性高、成本低廉、作用迅速、维持时间长等优点。本文就纳豆激酶的药理作用及市场应用前景作一综述,以期为纳豆激酶的进一步开发利用提供参考。     

纳豆激酶的制备及其降血脂功效研究

目的利用纳豆芽孢杆菌制备纳豆激酶,并评价纳豆激酶的降血脂功效。方法采用酪蛋白平板初筛-摇瓶发酵复筛的方法从市售纳豆中筛选获得高产纳豆激酶的纳豆枯草芽孢杆菌菌株,采用纤维蛋白平板法测定纳豆激酶酶活,以大豆为原料,利用该菌株制备纳豆激酶冻干粉。选取72只Wistar高脂模型大鼠进行降血脂功效研究,将其随机分为6组,分别为空白对照组、模型组、阳性对照组(普伐他汀钠片200 mg/kg)、纳豆激酶冻干粉高剂量组(360 mg/kg)、中剂量组(180 mg/kg)和低剂量组(90 mg/kg)。给药前后分别用自动生化分析仪测定总胆固醇(total cholesterol,TC)、甘油三酯(total triglyceride,TG)。结果成功发酵制得纳豆激酶冻干粉,大鼠喂养高脂饲料2周后其TC、TG水平较空白组显著升高(P<0.05),纳豆激酶冻干粉高、中、低剂量组及阳性对照组在给药6周后均能显著降低TC,TG水平(P<0.05)。结论本研究制备的纳豆激酶降血脂功效良好,为其作为降血脂药物和保健品奠定了基础。     

纳豆和纳豆激酶在预防和治疗疾病中的作用

纳豆是日本的传统食品,已食用千年。但从1987年,须见洋行教授道次发现纳豆中含有丰富的纳豆激酶,同时纳豆激酶还具有很强的纤溶作用之后,纳豆及其酶制剂便引起普遍关注。很多学者对其进行了药理学和治疗或预防疾病的研究,并发现其有纤溶治疗、抗菌、降血压、降胆固醇、降血脂和抗氧化等作用。与此同时一些食品生产和制造公司也对纳豆作了深加工。如日本的大和制药公司从纳豆中提取出纳豆激酶,冻干成粉剂,再制成软、硬胶囊作为保健食品推向市场,在美国、韩国和欧洲市场销售。目前已证明纳豆和纳豆激酶对一些疾病有很好的预防和治疗功效。现就其预防和治疗某些疾病的研究进展综述如下:     

纳豆激酶的提取分离纯化及研究新进展

 纳豆激酶是一种由纳豆芽胞杆菌产生的碱性丝氨酸蛋白酶,具有高效抗血栓、口服易吸收、无副作用等优点.本文对纳豆激酶的分子结构、生化特性、提取、分离与纯化等方面进行了综述,重点讨论了纳豆激酶的固体和液体发酵及层析法分离纯化,并介绍了纳豆激酶的最新研究进展.     

纳豆激酶的分离纯化及酶学性质研究

目的　分离纯化纳豆激酶并进行酶学性质研究。方法　从纳豆中分离纯化具有纤溶活性的纳豆激酶 ,采用氯化钠溶液浸提、硫酸铵盐析及 sephadex G- 1 5 0凝胶过滤分离纯化纳豆激酶 ,纯化倍数 5 0倍 ,纤维蛋白平板法测其比活。结果　纳豆激酶比活为 6 0 0 U·mg-1,回收率 40 %。酶学性质研究表明 ,最适反应温度为 5 0℃ ,5 5℃以下稳定 ,最适反应 p H为 8.0 ,在 p H 6～ 1 0溶液中基本稳定 ,分子量约 2 8k D。酶作用机理初探表明 ,纳豆激酶不仅具有纤溶性 ,还有抗凝血性。结论　纳豆激酶有可能成为新型溶栓药物     

纳豆激酶的纤溶活性及其机理研究

目的研究纳豆激酶的抗血栓作用 ,探讨其主要作用机理。方法通过药理实验方法观察纳豆激酶对体内急性血栓形成 ,以及对血液凝固系统全血凝血时间、凝血酶原时间、凝血酶时间、活化部分凝血活酶时间和血液中纤维蛋白原含量变化的影响。结果纳豆激酶提取物可对抗小鼠体内血栓形成 ,对内外源性凝血途径均有影响 ,同时有直接的溶栓作用。结论纳豆激酶具有较强的纤溶活性。     

纳豆激酶活性测定方法的比较

纳豆激酶是由纳豆芽孢杆菌经发酵产生的一种丝氨酸蛋白酶，可用于溶栓药物的开发。本文比较了两种测定纳豆激酶活性方法：琼脂糖——纤维蛋白平板法和枯草杆菌蛋白酶活力测定方法，为快速、准确地标示纳豆激酶的效价提供技术支撑。     

纳豆激酶的研究进展

纳豆激酶是由纳豆芽孢杆菌分泌的一种具有强烈纤溶作用的丝氨酸蛋白酶。作者就纳豆激酶的制备过程，基因结构、蛋白质结构、生物学功能及溶栓特性进行了综述，纳豆激酶经口服后可迅速入血，纤溶活性强，作用时间长，可望开发成新型口服防栓制剂，以供医疗和保健应用。     

Physiological response of carp,Cyprinus carpio,exposed to raw sewage containing fish processing wastewater

Physiological changes of carp exposed to raw sewage were investigated by the use of clinical examination methods. All carp exposed to raw sewage died within 6 h. On hour 48, 10, 40, and 90% of exposed carp survived in 60, 20, and 10% sewage, respectively. Carp exposed to 50 and 20% sewage increased ammonia, glucose, Mg, Cu, and Br, and decreased Fe and Zn in plasma. Even in 10% sewage, ammonia, glucose, and Br in plasma increased. Forty-eight hours of exposure to 50 and 20% sewage caused severe pathological changes in the gills. In the kidney, light abnormalities were observed at this time. When exposed to 50 and 20% sewage, atrioventricular conduction time and duration of electrical systole measured by electrocardiogram shortened briefly, and then extended gradually. In 50 and 20% sewage, heart rate and respiratory frequency increased briefly, and then decreased gradually. Cough reaction increased with the exposure. © 1997 by John Wiley & Sons, Inc. Environ Toxicol Water Qual 12: 1–9, 1997     

Alpinia zerumbet,a ginger plant with a multitude of medicinal properties: An update on its research findings

In this review, the botany and uses of Alpinia zerumbet (yan shan jiang) are described, and the current knowledge of its phytochemistry, pharmacological properties, and clinical trials is summarized. An important ginger crop in East Asia, A. zerumbet has many uses, both medicinal and non-medicinal. Leaves are used to produce essential oils and herbal teas. Rhizomes are consumed as spices, and stem fibers are made into paper, fabrics, and handicrafts. In Brazil, tea from A. zerumbet leaves is believed to have hypotensive, diuretic, and anti-ulcerogenic properties. This species possesses many medicinal properties due to its chemical constituents, including flavonoids, phenolic acids, phenylpropanoids, kava pyrones, sterols, and terpenoids. Extracts of A. zerumbet display antioxidant, antimicrobial, insecticidal, anthelmintic, tyrosinase and melanogenesis inhibitory, anti-atherogenic, anti-aging, anti-glycation, integrase and neuraminidase inhibitory, lifespan prolongation, hair growth promotion, anticancer, antidepressant, anxiolytic, anti-obesity, analgesic, anti-inflammatory, hypolipidemic, anti-ulcerogenic, anti-platelet, osteoblastic, osteogenic, thrombolytic, and cardiacarrhythmogenic activities. Essential oils of A. zerumbet leaves have antimicrobial, larvicidal, antinociceptive, hypotensive, vasorelaxant, myorelaxant, antispasmodic, antidepressant, anxiolytic, anti-neuraminidase, anti-atherogenic, anti-aging, anti-melanogenic, anti-tyrosinase, cytoprotective, cardiodepressive, antipsychotic, analgesic, anti-inflammatory, and tissue healing activities.Clinical trials conducted in Brazil showed that extracts of A. zerumbet have hypotensive and diuretic effects whereas topical application of the essential oil has positive therapeutic effects on patients with fibromyalgia. Spanning two continents of Asia and South America, A. zerumbetis truly a multi-purpose ginger plant with promising medicinal properties.     

Effects of typical and atypical antipsychotics on glucose–insulin homeostasis and lipid metabolism in first-episode schizophrenia

Rationale Glucose and lipid metabolism dysfunction is a significant side effect associated with antipsychotics. Although there are many studies about the linkages between drugs and metabolic dysfunction, most of these studies have compared the effects of two antipsychotics on only one metabolic measure: either glucose or lipid metabolism.Objectives The present study aimed to investigate the effects of clozapine, olanzapine, risperidone, and sulpiride on glucose and lipid metabolism in first-episode schizophrenia.Materials and methods One hundred twelve schizophrenics were assigned randomly to receive clozapine, olanzapine, risperidone, or sulpiride for 8 weeks. Planned assessments included body mass index (BMI), waist-to-hip ratio, fasting glucose, insulin, C-peptide, insulin resistance index (IRI), cholesterol, and triglyceride. All measures were collected at baseline and at the end of the 8-week treatment.Results After treatment, insulin, C-peptide, and IRI were significantly increased in the four groups, but not fasting glucose levels. Cholesterol and triglyceride levels were significantly increased in the clozapine and olanzapine groups. Patients treated with clozapine and olanzapine had higher fasting insulin, C-peptide, and IRI levels than those treated with risperidone and sulpiride. Among the four antipsychotics, the increases of mean BMI from high to low were as follows: clozapine, olanzapine, sulpiride, and risperidone.Conclusions This study confirmed that the four antipsychotic drugs were associated with an increase of insulin, C-peptide, and IRI. It was found that clozapine and olanzapine were associated with an increase in cholesterol and triglyceride levels. The effects of clozapine and olanzapine on the glucose and lipid metabolism outweighed those of risperidone and sulpiride.     

过量奥卡西平致定向力障碍及共济失调

1例6岁男性癫痫患儿,曾先后口服苯妥英钠、拉莫三嗪、丙戊酸钠、苯巴比妥治疗,因不能规律服药致使癫痫反复发作且进行性加重,家属自行给予其口服奥卡西平300 mg、3次/d,上述症状未再发作。但40 d后出现行走不稳、反应迟钝,且癫痫症状也加重。入院诊断为癫痫,全身强直-阵挛发作,奥卡西平致定向力障碍及共济失调。停用奥卡西平,给予丙戊酸钠、还原性谷胱甘肽、维生素C,次日癫痫得到控制。第8天定向力障碍及共济失调消失,癫痫未再发作,遂出院。出院后规律服用丙戊酸钠和氯硝西泮。随访1个月,未再出现癫痫发作、定向力障碍和共济失调。     

A review of anti-inflammatory,antioxidant, and immunomodulatory effects of Allium cepa and its main constituents

ContextAllium cepa L. (Liliaceae), known as onion, is consumed throughout the world. Onion and its derivatives including saponins, aglycones, quercetin, cepaenes, flavonoids, organosulfurs, and phenolic compounds, showed various pharmacological properties and therapeutic effects.ObjectiveAnti-inflammatory, antioxidant, and immunomodulatory effects of A. cepa and its main constituents, along with the underlying molecular mechanisms are presented.MethodsDatabases including, Web of Knowledge, Medline/PubMed, Scopus, and Google Scholar were checked for articles published between 1996 and the end of July 2020, using the key-words Allium cepa, quercetin, anti-inflammatory, antioxidant and immunomodulatory.ResultsA. cepa and its constituents mainly quercetin showed anti-inflammatory effects mediated via reduction of total and differential WBC counts, inhibition of chemotaxis of polymorphonuclear leukocytes, COX, and LOX pathways and prevented formation of leukotrienes and thromboxanes, prostaglandin E2 (PGE2) as onVCAM-1, NF-κB, MARK,d STAT-1, JNK, p38 and osteoclastogenesis. A. cepa and its derivatives showed antioxidant effect by decreasing lipid peroxidation, NAD(P)H, MDA, NO, LPO and eNOS but enhancing antioxidants such as SOD, CAT, GSH, GPx, GSPO, TrxR, SDH, GST and GR activities and thiol level. Immunomodulatory effects of the plant and quercetin was also shown by reduction of Th2 cytokines, IL-4, IL-5, and IL-13 as well as IL-6, IL-8, IL-10, IL-1β and TNF-α and IgE levels, but increased CD4 cells, IFN-γ level and IFN-γ/IL4 ratio (Th1/Th2 balance).ConclusionsThe effect of onion and its constituents on oxidative stress, inflammatory and immune system were shown indicating their therapeutic value in treatment of various diseases associated with oxidative stress, inflammation, and immune-dysregulation.     

Comparison of the gastrointestinal anatomy,physiology, and biochemistry of humans and commonly used laboratory animals

In addition to metabolic differences, the anatomical, physiological, and biochemical differences in the gastrointestinal (G.I.) tract of the human and common laboratory animals can cause significant variation in drug absorption from the oral route. Among the physiological factors, pH, bile, pancreatic juice, and mucus and fluid volume and content can modify dissolution rates, solubility, transit times, and membrane transport of drug molecules. The microbial content of the G.I. tract can significantly affect the reductive metabolism and enterohepatic circulation of drugs and colonic delivery of formulations. The transit time of dosage forms can be significantly different between species due to different dimensions and propulsive activities of the G.I. tract. The lipid/protein composition of the enterocyte membrane along the G.I. tract can alter binding and passive, active, and carrier-mediated transport of drugs. The location and number of Peyer's patches can also be important in the absorption of large molecules and particulate matter. While small animals, rats, mice, guinea pigs, and rabbits, are most suitable for determining the mechanism of drug absorption and bioavailability values from powder or solution formulations, larger animals, dogs, pigs, and monkeys, are used to assess absorption from formulations. The understanding of physiological, anatomical, and biochemical differences between the G.I. tracts of different animal species can lead to the selection of the correct animal model to mimic the bioavailability of compounds in the human. This article reviews the anatomical, physiological, and biochemical differences between the G.I. tracts of humans and commonly used laboratory animals.     

Neuropharmacological studies of phencyclidine (PCP)-induced behavioral stimulation in mice

A variety of drugs were screened to determine which were capable of blocking the behavioral stimulation produced in mice by acute administration of phencyclidine (PCP). Chlorpromazine and clozapine blocked PCP-induced stimulation, while haloperidol, reserpine, and alpha-methyl-p-tyrosine did not. The GABA receptor agonists imidazole acetic acid and muscimol blocked PCP, but other drugs that influence GABA, such as dipropylacetic acid, baclofen, and diazepam, were ineffective. Yohimbine and methysergide also blocked PCP in high dosages, but other drugs with comparable alpha-noradrenergic and serotonergic blocking properties (phentolamine, cyproheptadine, and cinnanserin) were ineffective. Cholinergic and anticholinergic drugs, beta-noradrenergic and opiate antagonists, and nonspecific sedatives and convulsants were also ineffective. These finding suggest that chlorpromazine, clozapine, yohimbine, and methysergide may share a property that is unlike their primary known modes of action on dopaminergic, alphanoradrenergic, and serotonergic neurotransmitter systems, and that this property accounts for their ability to block PCP. However, the effectiveness of GABA agonists appears to be mediated through direct activation of GABA receptors. It is suggested that chlorpromazine and imidazole acetic acid should be considered as possible drug treatments for PCP toxicity.     

聚氯乙烯和聚烯烃热塑性弹性体输液器对4种常用注射液稳定性及吸附性影响

目的：比较聚氯乙烯（PVC）输液器与聚烯烃热塑性弹性体（TPE）输液器对4种常用注射液的稳定性与吸附性的影响。方法：将乳酸环丙沙星氯化钠、左氧氟沙星氯化钠、乳酸左氧氟沙星氯化钠和托烷司琼氯化钠4种常用注射液迅速充满输液器并封存放置或正常流经输液器,采用HPLC法测定环丙沙星、左氧氟沙星和托烷司琼浓度,比较各药标示量变化,评价各药稳定性和输液器吸附性。结果：PVC和TPE输液器乳酸环丙沙星氯化钠注射液、左氧氟沙星氯化钠注射液、乳酸左氧氟沙星氯化钠注射液、托烷司琼氯化钠注射液最终（90 min）各药百分含量分别为94.11%,98.42%,98.02%,100.59%,101.91%,102.73%,99.04%,102.89%,2组含量变化无显著差异（P<0.05）,提示各药稳定。PVC和TPE输液器90 min各药百分含量分别为101.74%,100.21%,101.04%,99.37%和101.64%,103.10%,103.35%,103.27%,2组间含量变化无显著差异（P<0.05）,提示2种输液器吸附性相当。结论：PVC和TPE输液器不影响乳酸环丙沙星氯化钠注射液、左氧氟沙星氯化钠注射液、乳酸左氧氟沙星氯化钠注射液、托烷司琼氯化钠注射液的稳定性,对4种注射液中各药亦无吸附发生,可常规使用。     

Impact of Fusarium-Derived Mycoestrogens on Female Reproduction: A Systematic Review

Contamination of the world’s food supply and animal feed with mycotoxins is a growing concern as global temperatures rise and promote the growth of fungus. Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium fungi, is a common contaminant of cereal grains and has also been detected at lower levels in meat, milk, and spices. ZEN’s synthetic derivative, zeranol, is used as a growth promoter in United States (US) and Canadian beef production. Experimental research suggests that ZEN and zeranol disrupt the endocrine and reproductive systems, leading to infertility, polycystic ovarian syndrome-like phenotypes, pregnancy loss, and low birth weight. With widespread human dietary exposure and growing experimental evidence of endocrine-disrupting properties, a comprehensive review of the impact of ZEN, zeranol, and their metabolites on the female reproductive system is warranted. The objective of this systematic review was to summarize the in vitro, in vivo, and epidemiological literature and evaluate the potential impact of ZEN, zeranol, and their metabolites (commonly referred to as mycoestrogens) on female reproductive outcomes. We conducted a systematic review (PROSPERO registration CRD42020166469) of the literature (2000–2020) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The data sources were primary literature published in English obtained from searching PubMed, Web of Science, and Scopus. The ToxR tool was applied to assess risk of bias. In vitro and in vivo studies (n = 104) were identified and, overall, evidence consistently supported adverse effects of mycoestrogens on physiological processes, organs, and tissues associated with female reproduction. In non-pregnant animals, mycoestrogens alter follicular profiles in the ovary, disrupt estrus cycling, and increase myometrium thickness. Furthermore, during pregnancy, mycoestrogen exposure contributes to placental hemorrhage, stillbirth, and impaired fetal growth. No epidemiological studies fitting the inclusion criteria were identified.