单磷酰脂A对大鼠心肌缺血/再灌注损伤的保护作用

目的:探讨丝裂素活化蛋白激酶P38MAPK是否参与单磷酰脂A预处理的延迟保护作用.方法:建立大鼠心肌缺血/再灌注损伤模型.应用单磷酰脂A及P38的特异性抑制剂SB203580预处理,检测预处理后不同时间点P38磷酸化水平,并观察各组单磷酸酰酯A预处理24 h后缺血/再灌注心肌的梗死范围LDH释放.结果:预处理后24 h其心梗范围缩小,血浆LDH活性升高程度减轻(分别P＜0.01,vs I/R).用P38的特异性抑制剂SB203580可消除预处理后的延迟保护作用.结论:①单磷酰脂A预处理对24 h后缺血/再灌注心肌有保护作用.②P38参与单磷酰脂A预处理后的延迟保护作用,P38短暂而快速的激活可能是药物延迟保护作用的重要机制之一.     

环磷酰苷葡胺注射液治疗心功能不全121 例分析

目的：观察环磷酰苷葡胺注射液治疗充血性心力衰竭的疗效。方法：将243例充血性心力衰竭患者随机分为两组：观察组121例,对照组122例。对照组患者给予地高辛0．125-0．25mg或西地兰0．2mg加入注射用水20ml,每日1—2次静推,利尿剂给予速尿20—40mg。隔日口服或静推,同时补钾3次／日,疗程4—8周。观察组在应用上述药物的基础上,给予5％葡萄糖200—500ml加入环磷酰苷葡胺注射液60-80mg,1次／日静点,或25％葡萄糖加入环磷酰苷胺注射液90mg 1次／日静推,疗程4—8周。结果：两组心功能较治疗前明显改善。结论：环磷酰苷胺治疗充血性心力衰竭疗效确切,安全可靠,值得临床推广应用。     

新型磷酰胺类脲酶抑制剂对不同质地土壤尿素转化的影响

施用脲酶抑制剂是降低尿素水解、减少氨气挥发损失、提高作物氮(N)肥利用率的重要途径之一.采用室内恒温、恒湿模拟试验方法,在25 ℃黑暗条件下培养,研究新型磷酰胺类脲酶抑制剂N-丙基磷酰三胺(NPPT)的脲酶抑制效果,比较其与N-丁基磷酰三胺(NBPT)在不同尿素用量条件下不同质地土壤中对脲酶的抑制差异.结果表明: 在壤土和黏土中,尿素作用时间≤9 d,添加抑制剂可以将尿素水解时间延长3 d以上.砂土中,尿素分解过程相对缓慢,添加抑制剂显著降低土壤脲酶活性,抑制NH₄⁺-N生成.在培养期间,不同尿素用量条件下,脲酶抑制剂在不同质地土壤中的抑制效果表现为高施N量优于低施N量.培养第6天,在尿素用量250 mg N·kg^-1条件下,NBPT和NPPT在砂土中脲酶抑制率分别为56.3%和53.0%,在壤土中分别为0.04%和0.3%,在黏土中分别为4.1%和6.2%;尿素用量500 mg N·kg^-1,NBPT和NPPT在砂土中脲酶抑制率分别为59.4%和65.8%,在壤土中分别为14.5%和15.1%,在黏土中分别为49.1%和48.1%.不同质地土壤中脲酶抑制效果表现为砂土>黏土>壤土.不同抑制剂处理在培养期间土壤NH₄⁺-N含量呈现先上升后下降的趋势,而NO₃^--N含量和表观硝化率均呈现逐渐上升的趋势.与单施尿素处理相比,添加脲酶抑制剂NBPT和NPPT显著增加土壤中的残留尿素态N,降低NH₄⁺-N生成.新型脲酶抑制剂NPPT在不同质地土壤中的抑制效果与NBPT相似,是一款有效的脲酶抑制剂.     

一种新的卡那霉素残留检测方法

氨基糖苷 3′- O磷酰基转移酶Ⅱa (APH( 3′) -Ⅱa)具有磷酸化卡那霉素的功能 ,通过突变使APH( 3′) Ⅱa的催化活性丧失 ,同时保留与底物卡那霉素结合的功能 ,由此获得的突变型APH( 3′) - Ⅱa具有类似于抗体的特异性结合与识别卡那霉素分子的作用。采用戊二醛交联二步法制备了卡那霉素 辣根过氧化物酶结合物 (Kan HRP) ,把纯化后的APH( 3′) - Ⅱa蛋白包被到 96孔聚苯乙烯板上 ,通过竞争性ELISA的方法建立了一种新的卡那霉素残留检测方法。通过该方法可以检测到卡那霉素的最低残留量为 1 μg ml。     

羊骨胶原肽对大鼠腹腔巨噬细胞免疫能力的影响

目的 探究羊骨胶原肽(sheep bone collagen peptide,SBCP)对正常状态及脂多糖(lipopolysaccharide,LPS)活化状态巨噬细胞免疫能力的影响.方法 以不同剂量的SBCP作用于未经LPS活化和LPS活化的大鼠腹腔巨噬细胞,分别以MTT法和中性红法测定巨噬细胞代谢活力和吞噬活性,...     

11-脱氧18α-和18β-甘草次酸类抗癌复合物的制备和结构表征

为寻找新型肝靶向抗癌前药,将具有肝靶向特征的天然分子甘草次酸的半合成衍生物与抗癌药环磷酰胺的活性代谢物氮芥磷酰二氯偶联制成11-脱氧甘草次酸类两个目标化合物和7个中间体。化合物的化学结构用常规光谱分析法进行鉴定,对合成工艺、理化性质和光谱特征进行系统描述。本研究对甘草次酸类新型肝靶向抗癌前药的药理活性筛选奠定基础。     

硫酸盐活化复合体的分类及其功能

硫酸盐进入细胞内活化的第一步是ATP硫酸化酶(ATP sulfurylase,ATPS)催化硫酸盐与ATP反应生成腺苷-5’-磷酰硫酸(adenosine 5’-phosphosulfate,APS)和焦磷酸,此反应非常不易进行。研究发现某些ATPS可与硫酸盐同化代谢相关酶组成硫酸盐活化复合体(sulfate activating complex,SAC)而促进硫的同化。本文介绍了目前已发现的三类SAC:GTPase型SAC(GTPase type SAC)、APSK型SAC(APSK type SAC)和APSR型SAC(APSR type SAC),并对其促进APS合成的方式及目前的研究热点进行了讨论。     

精-甘-天冬-丝氨酸四肽对二磷酸腺苷诱导大鼠血小板活化的信号转导的影响

本工作在二磷酸腺苷（ＡＤＰ）活化的大鼠血小板上,观察精－甘－天冬－丝上肽（ＲＧＤＳ肽）对血小板聚集、蛋白磷酸化、蛋白激酶Ｃ和丝裂素活化蛋白激酶活性的影响。结果发现,５０μｍｏｌ／ＬＡＤＰ引起血小板聚集时,蛋白激酶Ｃ（ＰＫＣ０及丝裂经蛋白激酶（ＭＡＰＫ）活性增加,并引起９５和６６ｋＤ蛋白磷酸化。应用５０,１００和２００μｍｏｌ／ＬＲＧＤＳ肽与基共同孵育,呈浓度依赖地抑制ＡＤＰ引起的血小板聚集和对ＰＫ     

泛肽系统的组成和功能(一)—系统组成、底物识别与蛋白质泛肽化

泛肽（Ｕｂｉｑｕｉｔｉｎ,简称Ｕｂ）是一个由７６个氨基酸残基组成的非常保守的小蛋白质。泛肽依赖性的蛋白质降解途径（Ｕｂｉｑｕｉｔｉｎ＿ｄｅｐｅｎｄｅｎｔｐｒｏｔｅｏｌｙｔｉｃｐａｔｈｗａｙ）是目前已知的最重要的、有高度选择性的蛋白质降解途径。泛肽系统由Ｕｂ、Ｕｂ活化酶、Ｕｂ结合酶、Ｕｂ＿蛋白质连接酶、Ｕｂ＿Ｃ末端水解酶和２６Ｓ蛋白酶体组成。本文详细地介绍了泛肽系统各个组成部分的种类、结构与功能,蛋白质泛肽化及其降解机制和底物识别模式。     

肽酰精氨酸的翻译后修饰

肽酰精氨酸残基甲基化作用是细胞质与细胞核内蛋白质翻译后修饰的普遍方式。精氨酸残基甲基化蛋白质与许多细胞生物学过程有关,包括转录调节、RNA代谢和DNA损伤修复等。生物体内精氨酸N-甲基转移酶类、肽酰精氨酸脱亚氨酶类与JMJD6等催化肽酰精氨酸残基进行甲基化、瓜氨酸化和去甲基化的动态修饰。这种动态修饰对细胞生物学功能有重要调节作用。     

Thermodynamic properties of oxidoreductase, transferase, hydrolase, and ligase reactions

Transferases formally couple together two oxidoreductase reactions or two hydrolase reactions. Therefore the thermodynamic properties of transferase reactions can be calculated from differences between thermodynamic properties of two oxidoreductase or two hydrolase reactions. Ligases couple together two hydrolase reactions, and so their thermodynamic properties can be calculated from differences between two hydrolase reactions. These relationships are demonstrated by calculating standard transformed Gibbs energies of reaction and the changes in binding of hydrogen ions at pHs 5-9 of a number of oxidoreductase, transferase, hydrolase, and ligase reactions by use of the data base BasicBiochemData2 and its recent extensions. Coupling is not restricted to two reactions, and an example is given of the coupling of three reactions.     

Cellular defence reactions and their depression in insects]

In insects the main cellular defence reactions are phagocytosis and encapsulation of foreign bodies. Free cells of haemolymph called haemocytes are the effectors of these reactions. They are achieved under the control of humoral factors of the plasma or of the serum. Humoral factors are able to enhance or to decrease the cellular defence reactions. As in mammals, potential parasites or pathogens need to avoid or to inhibit the defence reactions before developing inside the insect body. As an example of the depression of immunity induced by a parasite we will study the relationships between an insect and a nematobacterial complex.     

Adding handles to unhandy substrates: anaerobic hydrocarbon activation mechanisms

In spite of their chemical inertness, hydrocarbons are degraded by microorganisms in the complete absence of oxygen. As all known aerobic hydrocarbon degradation pathways start with oxygen-dependent reactions, hydrocarbon catabolism in anaerobes must be initiated by novel biochemical reactions. In recent years, the enzymes catalyzing oxygen-independent activation of several hydrocarbons have been identified. Surprisingly, a variety of reactions seems to be employed to overcome the activation barrier of different hydrocarbons. This review presents the current understanding on some of these reactions and the associated degradation pathways: oxygen-independent hydroxylation as employed in ethylbenzene metabolism, fumarate addition to methyl or methylene carbons in toluene or alkane degradation, and only recently discovered reactions such as methylation of naphthalene or anaerobic methane oxidation via reverse methanogenesis.     

The Limulus sperm motility-initiating peptide initiates acrosome reactions in sea water lacking potassium

During fertilization in Limulus, the spermatozoa first attach to the egg and then undergo an acrosomal reaction. In this reaction, the acrosomal vesicle exocytoses, and a long, preformed acrosomal filament is extruded (and subsequently penetrates the egg chorion). The egg surface component that triggers the acrosome reaction has not yet been solubilized; therefore, previous studies have examined either spontaneous acrosome reactions or acrosome reactions that were triggered by eggs (or insoluble egg fragments), elevated extracellular Ca2+, or Ca2+ ionophores. In this study, we report a new method for initiating acrosome reactions in Limulus sperm. When the Limulus sperm motility-initiating peptide (SMI) is added to sperm in K+-free sea water, greater than 90% acrosome reactions are initiated within 5 min. However, less than 5% acrosome reactions occur either in K+-free sea water lacking SMI or when SMI is added to sperm in either normal sea water or K+- and Ca2+-free sea water. Experiments with K+ ionophores (nigericin and valinomycin), a K+ channel blocking agent (tetraethyl ammonium), an Na+ ionophore (monensin), and reagents that increase the intracellular pH (monensin, nigericin, and NH4Cl) indicate that changes in intracellular K+, Na+, or H+ do not mediate SMI-initiated acrosome reactions. The K+/Ca2+ ratio determines whether or not SMI will initiate acrosome reactions, with greater than 50% acrosome reactions being initiated when this ratio is below 0.3. In that K+ movement does not appear to be the critical event, possibly the K+/Ca2+ ratio either determines the rate of Ca2+ entry or controls the conformation of sperm surface molecules to allow SMI to initiate acrosome reactions in low K+.     

Validity of anecdotal reports of suspected adverse drug reactions: the problem of false alarms

Suspected adverse drug reactions first reported in 1963 in the “British Medical Journal,” the “Lancet,” the “Journal of the American Medical Association,” and the “New England Journal of Medicine” were reviewed 18 years later to assess their initial validity and subsequent verification. Of 52 first reports, five were deliberate investigations into potential or predictable reactions, and in each case causality was reasonably established; the other 47 reports were essentially anecdotal. Of these 47 reports, 14 related to categories of adverse reaction where false-positive reports were unlikely: immediate reactions, local reactions, and known reactions caused by a different mode of administration or a brand previously thought or claimed to be safe. The problem of false alarms rose in the remaining types of reactions: general reactions that did not occur immediately after administration and arose for the first time with a new chemical entity. Of 33 reports of such suspected adverse reactions, validity was satisfactorily established in 14 cases on the basis of rechallenge, predictability from known pharmacology, or the unique nature of the reaction. Of the remaining 19 reports, further verification still has not been satisfactorily established in 12. Seven of these possible false alarms were haematological reactions.Although 35 of the 47 anecdotal reports were clearly correct, of the 19 reports that were not reasonably validated at the time of the report, only seven were subsequently verified. This suggests that agencies monitoring adverse drug reactions should adopt criteria for assessing the validity of first reports of suspected adverse reactions. Such criteria should include: reactions on rechallenge, a pharmacological basis for the adverse reaction, immediate acute reactions, local reactions at the site of administration, reactions with a new route of administration of a drug known to provoke such reactions by another route, and the repeated occurrence of very rare events.     

Histochemical reactions of gastrointestinal mucosubstances with orcein, high iron diamine and Alcian blue after prior oxidation of tissue sections.

The histochemical orcein reaction (orc) for mucosubstances in tissue samples from the human gastrointestinal tract was compared with PAS, high iron diamine (HID) and Alcian blue reactions at pH 1.0 or 2.5 (AB 1 and AB 2.5). Orc, HID and AB 1 reactions were performed also with prior oxidation of the tissue sections with potassium permanganate or performic acid (ox-orc, ox-HID and ox-AB reactions, respectively). Orc reaction stained mucosubstances similarly to HID and AB 1; only the brush border and goblet cells in the colon were stained. The reactions of the mucosubstances obtained with ox-orc differed from those with PAS, HID, AB 1 or AB 2.5 but were similar to those with ox-HID or ox-AB; the mucosubstances in the brush border and the goblet cells in the colon and small bowel and in the foveolar epithelium of the stomach were strongly stained. Pyloric and cardiac glands were stained faintly with ox-orc but not with ox-HID or ox-AB. Brunner's glands were negative with ox-orc, ox-HID and ox-AB reactions. It was assumed that the orc reaction stains, like HID or AB 1, sulphate groups in epithelial mucosubstances, and that sulphonic acid residues, resulting from oxidation of disulphide groups in the protein core of mucus glycoproteins, are responsible for the ox-orc as well as for the ox-HID and ox-AB reactions.     

Effects of cyclophosphamide on the expression and induction of delayed hypersensitivity.

Erythematous delayed reactions without induration, presumably assigned to Jones-Mote type, were characterized by the resistance to treatment with cyclophosphamide (CY) before elicitation or immunization in guinea pigs immunized with BGG in IFA or CFA. CY-treatment before elicitation converted delayed erythematous reactions from negative to positive at late intervals after immunization with BGG in IFA. Such a treatment augmented erythematous delayed reactions in animals immunized with BGG in CFA, but abolished induration at the reaction sites. CY-treatment before elicitation or immunization reduced the numbers of basophils at the reaction sites, although erythematous delayed reactions were augmented. Effector T cells responsible for delayed erythematous reaction without induration appear to persist for a long period of time after immunization in the presence of antibody production or tuberculin hypersensitivity and the expression of their function may be inhibited by suppressive mechanisms.     

Identifying and understanding drug allergies

Drug hypersensitivity reactions frequently occur in hospitalized and out-patients. Clinical presentations are numerous and heterogeneous, from a mild urticaria to a dramatic anaphylactic shock and an extensive bullous skin disease. Allergic reactions are unpredictable reactions, related to immunologic mechanisms. Some reactions mimic allergic reactions but no drug specific antibody or T cell proliferation can be demonstrated. A true diagnosis is rarely set up and the tools for it are lacking. In this review, we will focus on the available epidemiological data concerning these reactions, including data on incidence and mortality and on the most recent advances in the pathophysiology and allergy diagnosis of drug hypersensitivity reactions.     

Schiff and pseudo-Schiff reagents: the reactions and reagents of Hugo Schiff,including a classification of various kinds of histochemical reagents used to detect aldehydes

During the 1860’s, Hugo Schiff studied many reactions between amines and aldehydes, some of which have been used in histochemistry, at times without credit to Schiff. Much controversy has surrounded the chemical structures and reaction mechanisms of the compounds involved, but modern analytical techniques have clarified the picture. I review these reactions here. I used molecular modeling software to investigate dyes that contain primary amines representing eight chemical families. All dyes were known to perform satisfactorily for detecting aldehydes in tissue sections. The models verified the correct chemical structures at various points in their reactions and also determined how decolorization occurred in those with “leuco” forms. Decolorization in the presence of sulfurous acid can occur by either adduction or reduction depending on the dye. The final condensation product with aldehyde was determined to be either a C-sulfonic acid adduct on the carbonyl carbon atom or an aminal at the same atom. Based on the various outcomes, I have placed the dyes and their reactions into five categories. Because Hugo Schiff studied the reactions between aldehydes and amines with and without various acids or alcohol, it is only proper to call each of them Schiff reactions that used various types of Schiff reagents.     

Adverse reactions to 1975 bivalent influenza vaccine in children.

A questionnaire survey was undertaken to investigate incidence and types of reactions to a bivalent, zonally purified, killed influenza vaccine administered to 155 children aged 1 to 18 years in 1975. Local or systemic reactions or both occurred in 42 children (27%). However, these reactions were not considered serious and should not constitute a major drawback to future influenza programs in children under 3 years of age.