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。     

A pilot study of heavy metal concentration in various environments and fishes in the Upper Sakarya River Basin,Turkey

In this study, concentration of lead, cadmium, copper, cobalt, nickel, and manganese were measured in water, sediment, and fish (Cyprinus carpio and Barbus plebejus) samples at the upper Sakarya river basin in Sept. 1995–1996 period. Also, physical parameters of selected stations in the Sakarya river were measured. Mean concentrations of lead, cadmium, copper, nickel, and manganese differed between water, sediment, and fish samples by seasons. Mean concentrations of lead, cadmium, and cobalt increased in sediment samples in October and August. In water samples only cadmium and cobalt increased in October whereas lead and copper increased in August. Also, high levels of manganese concentrations were detected in water and sediment samples and fish tissue during the study. ©1999 John Wiley & Sons, Inc. Environ Toxicol 14: 367–373, 1999     

杜仲和西伯利亚人参的化学成分及药理作用

The bark and leaves of Eucommia ulmoides Oliv(Eucommiaceae) and "Siberian ginseng" (Ezoukogi inJapanese) prepared from the root bark or stem bark ofEleutherococcus senticosus Maxim (Acanthopanax senti-cosus Harms) have been used as tonic and anti-stressdrug. The extracts of Eucommia showed anti-hyperten-sive, anti-complementary, anti-oxidative, and anti-gastric ulcer effects, and promting collagen synthesis,accelating granuloma formation, and other pharmacologi-cal effects. The Siberian ginseng exhibited anti-fatigue,anti-stress, immuno-enhancing effect, CNS activity, andanti-depressive effect. By now, 40, 28, and 10 com-pounds have been isolated from Eucommia ulmoidesbark, Eucommia ulmoides leavs, and Siberian ginseng,respectively, and their structures were elucidated. Theirpharmacological activities were mainly due to lignans andiridoid glycosides.     

医用纳米与基因药物口服化的探索

口服给药乃是疾病防治的主要手段之一,由于方便、有效、舒适、安全受到患者与医生的普遍欢迎。但是大分子药物在肠道的摄取和吸收仍然缺乏详尽的有效研究。最近十多年来，利用纳米技术开展大分子药物在肠道的摄取和吸收取得了可喜的进展。本文系统地阐述纳米颗粒、蛋白转导、纳米微粒在肠道的摄取位点、摄取细胞种类与吸收的关系。本文对口服给药基因治疗这一新颖的给药途径的探索予以重点介绍，并讨论了目前口服基因药物传递及基因表达的主要障碍和未来发展趋势。     

Novel modes of antifungal drug administration

Administration of antifungals by routes other than that for which the agent was designed or approved have been utilised in attempts to provide directed therapy, reduce adverse effects and improve drug penetration into selected infection sites, such as the central nervous system, lungs and peritoneum. The most widely investigated agent utilising a novel method of drug delivery is amphotericin B. Dose forms for this agent include topicals (aerosol, nasal spray, irrigations, pastes, absorbable sponges, impregnated bone cement and gelatin), oral dosage forms (solutions, suspensions, tablets and so on) and ophthalmic preparations (drops, ointments and injections). Amphotericin B has been administered by routes such as oral, endobronchial, intrathecal, intracisternal, intra-articular, intraperitoneal, ophthalmic and as an antibiotic ‘line lock’. Nystatin has been administered as an aerosol, percutaneous paste and bladder washes. Azoles, such as miconazole, fluconazole, ketoconazole and posaconazole, have been administered by novel methods but to a lesser degree. Most of these reports involve miconazole. The dose forms and routes of administration for azoles have included irrigants (bladder, joint), ophthalmic preparations (eye drops, intraocular injections, ointments), impregnated bone cement, endobronchial and intrathecal administration. Finally, both methylene blue (bladder washes) and flucytosine (peritoneal lavage, ophthalmic eye drops) have also been employed. Adequate evaluations of both the safety and efficacy of these therapies are most often hindered by prior or concomitant antifungal therapies, comorbidities and the lack of controlled clinical trials. In addition, the availability of newer treatment options, which demonstrate significant improvement in drug distribution and treatment-related adverse effects make many such novel modes of administration less practical or necessary. In contrast, the inhalation of antifungal aerosols, such as amphotericin B, is rapidly becoming a viable prophylactic option.     

Caffeine and diazepam: Separate and combined effects on mood,memory, and psychomotor performance

The effects of caffeine and diazepam on several mood, cognitive, learning, memory, and psychomotor tasks were investigated in a double-blind study of 108 young healthy adults who were randomly assigned to nine treatments; oral administration of caffeine (0, 3 and 6 mg/kg), diazepam (0, 0.15, and 0.30 mg/kg) and their combinations. Subjects completed a battery of tasks once before and twice after administration of the drugs. Caffeine alone showed no effects on cognitive, learning, and memory performance, but impaired fine motor coordination and increased anxiety and tenseness. Diazepam alone produced sedation, lowered other ratings of subjective moods, and impaired cognitive, learning, and memory performance. The two drugs did not antagonize the effects of each other, except in the symbol cancellation task.     

齐墩果酸和熊果酸的神经精神药理作用研究进展

齐墩果酸和熊果酸同属五环三萜酸类化合物,它们又是同分异构体.药理作用几乎相同,都具有抗氧化、抗炎、免疫调节、抗肿瘤、抗微生物、保肝、抗糖尿病、调脂、减肥、抗动脉粥样硬化作用.综述齐墩果酸和熊果酸保护神经细胞、镇痛、抗焦虑、抗神经分裂症、抗抑郁、改善学习记忆等神经精神药理作用,为齐墩果酸和熊果酸防治老年痴呆、帕金森病和抑郁症的研发提供依据.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Mimetics of Hormetic Agents: Stress-Resistance Triggers

Mimetics of hormetic agents offer a novel approach to adjust dose to minimize the risk of toxic response, and maximize the benefit of induction of at least partial physiological conditioning. Nature selected and preserved those organisms and triggers that promote tolerance to stress. The induced tolerance can serve to resist that challenge and can repair previous age, disease, and trauma damage as well to provide a more youthful response to other stresses. The associated physiological conditioning may include youthful restoration of DNA repair, resistance to oxidizing pollutants, protein structure and function repair, improved immunity, tissue remodeling, adjustments in central and peripheral nervous systems, and altered metabolism. By elucidating common pathways activated by hormetic agent’s mimetics, new strategies for intervention in aging, disease, and trauma emerge. Intervention potential in cancer, diabetes, age-related diseases, infectious diseases, cardiovascular diseases, and Alzheimer’s disease are possible. Some hormetic mimetics exist in pathways in primitive organisms and are active or latent in humans. Peptides, oligonucleotides, and hormones are among the mimetics that activate latent resistance to radiation, physical endurance, strength, and immunity to physiological condition tolerance to stress. Co-activators may be required for expression of the desired physiological conditioning health and rejuvenation benefits.     

Chemical induction of brain tumors in rats by nitrosoureas: Molecular biology and neuropathology

Nitrosourea-induced rat brain tumors are among the best investigated experimental systems for neuropathological, biochemical, diagnostic and therapeutic research in neurooncology. This review summarizes data concerning molecular biology, neuropathology, in vitro studies, transplantation models and antigen expression of experimental gliomas in inbred rat strains. Systemic application of nitroso-compounds, i.e., ENU and MNU, leads to the alkylation of DNA bases, which, due to a specific repair deficiency, persist in the nervous system remarkably longer than in other organs. The hypothesis is that alkylated bases cause base-mispairing and point mutations followed by uncontrolled expression of oncogenes and growth factor receptors, resulting in permanent cell proliferation. Thus, nitrosoureas are considered to be biological hazards, especially as potent endogenous and exogenous neurotoxins. Neuropathology and growth characteristics of these experimental tumors are comparable to human malignant gliomas. Similar to the human WHO grade III and IV tumors, they reveal cellular pleomorphism, elevated mitotic activity, proliferation of blood vessels, blood-brain barrier disturbances, necrosis and invasiveness. Nitrosourea-induced brain tumors have been used in investigations concerning glioma growth and regression, brain edema, glioma immunology, metabolism, regional biochemistry, and experimental therapy. The studies included conventional morphology, immunohistochemistry, -cytochemistry and -electronmicroscopy, morphometry, cell culture, hybridoma technology, tumor transplantation and regional imaging by autoradiography, bioluminescence, magnetic resonance and immunoscintigraphy.     

Heavy metals in raw,fried and grilled Mediterranean finfish and shellfish

The effect of domestic pan-frying and grilling on Cd, Cr, Cu, Fe, Hg, Ni, Pb and Zn content of popular small Mediterranean finfish and shellfish was studied. The species selected -namely anchovy, bogue, hake, picarel, sardine, sand smelt, stripped mullet, Mediterranean mussel, shrimp and squid- are among the most commonly marketed and consumed in Greece and most of the Mediterranean countries. Both culinary practices examined resulted in increased metals concentrations compared to those of raw samples, the increment being inversely related to fish size and -in most cases- being more extended in pan-frying. The consumption of cooked seafood is expected to provide significant amounts of Fe and Zn followed, in decreasing order, by Cr, Cu and Ni. In addition, the estimation of (a) weekly intakes and (b) target hazard quotients for the toxic elements Cd, Hg and Pb revealed that the cooked fish and shellfish do not pose any health risk for the consumers.