BACKGROUND & AIMS: Histochemical, immunohistochemical, and biochemical evidence is reported showing that the ink gland of the cuttlefish Sepia officinalis contains a calcium-dependent isoform of nitric oxide synthase as well as an NMDA R1 receptor subunit localized for the most part in the immature inner cells of the epithelial layer of the gland. These results may be taken to implicate a hitherto unrecognized regulatory role of the glutamate-nitric oxide pathway in the maturation and metabolic activity of melanin-producing cells in the cephalopod defense system.

背景与目标： 据组织化学，免疫组化和生物化学证据显示，墨鱼乌贼墨the的墨腺含有一氧化氮合酶的钙依赖性同种型，以及大部分位于上皮未成熟内细胞中的NMDA R1受体亚基。腺体层。这些结果可能暗示了迄今为止尚未认识到的谷氨酸一氧化氮途径在头足防御系统中黑色素生成细胞的成熟和代谢活性中的作用。

BACKGROUND & AIMS: :Infused CD34 cell count has a significant impact on transplant outcome. In this retrospective study, we aimed to analyze the impact of donor iron parameters on peripheral blood stem cell (PBSC) collection. A total of 303 related donors were included in the study. The mobilization regimen, recombinant G-CSF, was given for four consecutive days. A CD34+ cell count below 2×106/kg was defined as mobilization failure which was demonstrated in 23 donors (7.6%). Mobilization failure was more frequent in female donors than male donors (13.7% vs 3.4%). Body mass index, mean corpuscular volume, hemoglobin and ferritin levels were found to be lower in donors with mobilization failure. Body mass index was significantly correlated with PBSC count on the 4th day of G-CSF. Body mass index, male gender, mean corpuscular volume and ferritin levels had significant impact on PBSC count. Although PBSC count was found to be similar between female and male donors, female gender was shown to have an adverse impact on PBSC collection, which may be attributed to lower body weight and concurrent iron deficiency.

背景与目标： ：注入的CD34细胞数量对移植结果有重要影响。在这项回顾性研究中，我们旨在分析供体铁参数对外周血干细胞（PBSC）收集的影响。总共303名相关捐助者被纳入研究。连续四天给予了动员方案，即重组G-CSF。低于2×106 / kg的CD34细胞计数被定义为动员失败，这在23个捐献者（7.6％）中得到证实。女性捐赠者的动员失败率比男性捐赠者更高（13.7％vs 3.4％）。发现动员失败的献血者的体重指数，平均红细胞体积，血红蛋白和铁蛋白水平较低。体重指数与G-CSF第4天的PBSC计数显着相关。体重指数，男性，平均红细胞体积和铁蛋白水平对PBSC计数有显着影响。尽管发现雌性和雄性供体之间的PBSC计数相似，但显示出性别对PBSC收集有不利影响，这可能归因于体重减轻和同时发生的铁缺乏症。

BACKGROUND & AIMS: :Urease, a nickel-containing metalloenzyme, was the first enzyme to be crystallized and has a prominent position in the history of biochemistry. In the present study, we identified a nickel urease gene cluster, ureABCEFGDH, in Bacillus paralicheniformis ATCC 9945a and characterized it in Escherichia coli Enzymatic assays demonstrate that this oxygen-stable urease is also an iron-containing acid urease. Heterologous expression assays of UreH suggest that this accessory protein is involved in the transmembrane transportation of nickel and iron ions. Moreover, this iron-containing acid urease has a potential application in the degradation of urea in rice wine. The present study not only enhances our understanding of the mechanism of activation of urease but also provides insight into the evolution of metalloenzymes.IMPORTANCE An iron-containing, oxygen-stable acid urease from B. paralicheniformis ATCC 9945a with good enzymatic properties was characterized. This acid urease shows activities toward both urea and ethyl carbamate. After digestion with 6 U/ml urease, approximately 92% of the urea in rice wine was removed, suggesting that this urease has great potential in the food industry.

背景与目标： ：脲酶，一种含镍的金属酶，是第一个被结晶的酶，在生物化学史上占有重要地位。在本研究中，我们在副芽孢杆菌ATCC 9945a中鉴定了镍脲酶基因簇ureABCEFGDH，并在大肠杆菌中对其进行了表征。酶法测定表明，该氧稳定脲酶也是一种含铁的酸性脲酶。 UreH​​的异源表达测定表明该辅助蛋白与镍和铁离子的跨膜运输有关。此外，这种含铁的酸性脲酶在米酒中尿素的降解中具有潜在的应用。本研究不仅增进了我们对脲酶激活机理的理解，而且为金属酶的发展提供了见识。重要特征表征了副枝芽孢杆菌ATCC 9945a具有良好的酶学性质的含铁，氧稳定的酸性脲酶。该酸性脲酶显示出对脲和氨基甲酸乙酯的活性。用6 U / ml尿素酶消化后，黄酒中约有92％的尿素被去除，这表明该尿素酶在食品工业中具有巨大的潜力。

BACKGROUND & AIMS: :Data are presented indicating that the growth of 5 out of 5 murine lymphoid tumors can be inhibited in a synergistic fashion in vitro by combined treatment with the iron chelator deferoxamine (DFO) and an immunoglobulin G (IgG) monoclonal anti-transferrin receptor antibody (ATRA). A two-way dose/response analysis shows that the ATRA becomes more efficient as an inhibitor with increasing doses of DFO. Flow cytometric studies further support the view that IgG ATRAS impair transferrin receptor (TR) function by causing TR down-modulation and degradation, even when the presence of DFO acts to promote increased cell surface TR expression. It is also shown that an IgG ATRA is nearly as effective as an IgM ATRA in inhibiting tumor cell growth when used in combination with DFO. Finally, studies with the iron chelator picolinic acid show that it produces only additive, or very slightly supra-additive, effects when used in combination with the ATRA. Therefore, these studies not only continue to suggest that combination chelator/ATRA therapy warrants further investigation as a tool in the therapy of hematopoietic malignancies, but also make the following new points: (1) the clinically familiar iron chelator deferoxamine, but not all iron chelators, produces synergistic inhibition of tumor growth in vitro with ATRAS; and (2) IgG ATRAS, which may be clinically more attractive reagents than IgA or IgM ATRAS because of better access to extra vascular tissue spaces, have unexpectedly been found to function as powerful growth inhibitors when used in combination with DFO.

背景与目标： ：数据表明，通过与铁螯合剂去铁胺（DFO）和免疫球蛋白G（IgG）单克隆抗转铁蛋白受体抗体联合治疗，可以在体外以协同方式抑制5种鼠类淋巴瘤中5种的生长。 ATRA）。双向剂量/响应分析表明，随着DFO剂量的增加，ATRA作为抑制剂的效率更高。流式细胞术研究进一步支持这样一种观点，即即使存在DFO时，IgG ATRAS也会通过引起TR下调和降解而损害运铁蛋白受体（TR）的功能，即使DFO的存在会促进细胞表面TR表达的增加。还显示了当与DFO组合使用时，IgG ATRA在抑制肿瘤细胞生长方面几乎与IgM ATRA一样有效。最后，对铁螯合剂吡啶甲酸的研究表明，当与ATRA结合使用时，它仅产生加成或极轻微的超加成作用。因此，这些研究不仅继续表明，螯合剂/ ATRA组合疗法作为造血系统恶性肿瘤治疗的工具值得进一步研究，而且还提出了以下新观点：（1）临床上熟悉的铁螯合剂去铁胺，但并非所有铁螯合剂，在体外与ATRAS产生协同抑制肿瘤生长的作用； （2）IgG ATRAS在临床上可能比IgA或IgM ATRAS具有更强的吸引力，因为它可以更好地进入多余的血管组织空间，与DFO组合使用时，出乎意料地起到了强大的生长抑制剂的作用。

BACKGROUND & AIMS: :The diffusible messenger, nitric oxide plays multiple roles in neuroprotection, neurodegeneration and brain plasticity. Its involvement in neurogenesis has been disputed, on the basis of results on models in vivo and in culture. We report here that pharmacological blockade of nitric oxide production in rat pups resulted, during a restricted time window of the first three postnatal days, in increased cerebellar proliferation rate, as assessed through tritiated thymidine or BrdU incorporation into DNA. This was accompanied by increased expression of Myc, a transcription factor essential for cerebellar development, and of the cell cycle regulating gene, cyclin D1. These effects were mediated downstream by the nitric oxide-dependent second messenger, cGMP. Schedules of pharmacological NO deprivation targeted to later developmental stages (from postnatal day 3 to 7), no longer increased proliferation, probably because of partial escape of the cGMP level from nitric oxide control. Though limited to a brief temporal window, the proliferative effect of neonatal nitric oxide deprivation could be traced into adulthood. Indeed, the number of BrdU-labeled surviving cells, most of which were of neuronal phenotype, was larger in the cerebellum of 60-day-old rats that had been subjected to NO deprivation during the first three postnatal days than in control rats. Experiments on cell cultures from neonatal cerebellum confirmed that nitric oxide deprivation stimulated proliferation of cerebellar precursor cells and that this effect was not additive with the proliferative action of sonic hedgehog peptide. The finding that nitric oxide deprivation during early cerebellar neurogenesis, stimulates a brief increase in cell proliferation may contribute to a better understanding of the controversial role of nitric oxide in brain development.

背景与目标： ：弥散性信使，一氧化氮在神经保护，神经变性和脑可塑性中起多种作用。根据体内和培养模型的结果，它在神经发生中的作用一直存在争议。我们在这里报告说，通过natal化胸腺嘧啶脱氧核苷或BrdU掺入DNA评估，在大鼠出生后前三天的有限时间窗内，在大鼠幼崽中产生一氧化氮的药理学阻断作用导致小脑增殖率的提高。这伴随着Myc和小细胞周期调节基因cyclin D1的表达增加，Myc是小脑发育所必需的转录因子。这些效应是由依赖一氧化氮的第二信使cGMP介导的。针对发育后期（从出生后第3天到第7天）的药理性NO剥夺时间表不再增加增殖，这可能是因为cGMP水平从一氧化氮控制中部分逃逸了。尽管仅限于短暂的时间窗，但新生儿一氧化氮剥夺的增殖作用可追溯至成年期。实际上，在出生后前三天被NO剥夺的60日龄大鼠小脑中，BrdU标记的存活细胞的数量多于对照大鼠，其中大多数为神经元表型。新生儿小脑细胞培养的实验证实，一氧化氮的缺乏会刺激小脑前体细胞的增殖，并且这种作用不会与声波刺猬肽的增殖作用相加。小脑早期神经发生过程中一氧化氮的缺乏会刺激细胞增殖的短暂增加，这一发现可能有助于更好地理解一氧化氮在脑发育中的作用。

BACKGROUND & AIMS: :We investigate the effects of detergent on the kinetics and oligomeric state of allene oxide synthase (AOS) from Arabidopsis thaliana (CYP74A1). We show that detergent-free CYP74A1 is monomeric and highly water soluble with dual specificity, but has relatively low activity. Detergent micelles promote a 48-fold increase in k(cat)/K(m) (to 5.9 x 10(7)M(-1)s(-1)) with concomitant changes in the spin state equilibrium of the haem-iron due to the binding of a single detergent micelle to the protein monomer, which is atypical of P450 enzymes. This mechanism is shown to be an important determinant of the substrate specificity of CYP74A1. CYP74A1 may be suited for structural resolution of the first plant cytochrome P450 and its 9-AOS activity and behaviour in vitro has implications for its role in planta.

背景与目标： ：我们研究了洗涤剂对拟南芥（CYP74A1）的氧化烯合酶（AOS）动力学和低聚状态的影响。我们显示不含洗涤剂的CYP74A1是单体的，具有双特异性的高度水溶性，但活性相对较低。洗涤剂微团促进k（cat）/ K（m）增加48倍（至5.9 x 10（7）M（-1）s（-1）），同时血红素铁的自旋态平衡发生变化由于单个去污剂胶束与蛋白质单体结合，这是非典型的P450酶。已显示该机制是CYP74A1底物特异性的重要决定因素。 CYP74A1可能适合第一种植物细胞色素P450的结构解析，其9-AOS活性和体外行为对其在植物中的作用具有影响。

BACKGROUND & AIMS: :1. Intravital microscopy of rabbit tenuissimus muscle microvasculature was used for in vivo studies of the role of endogenous nitric oxide (NO) in local vascular control. Derivatives of arginine were applied topically in order to modulate the formation of NO from L-arginine. 2. L-NG-monomethylarginine (L-NMMA) (10-100 microM), but not D-NG-monomethylarginine (D-NMMA), dose-dependently reduced microvascular diameters. The vasoconstriction induced by L-NMMA (100 microM) was prevented by pretreatment with L-arginine (1 mM) but not with D-arginine (1 mM). Intravenous infusions of L-arginine (300 mg kg-1) reversed the effect of L-NMMA (100 microM). L-Arginine or D-arginine applied topically at 1 mM per se had no effect on microvascular diameters. 3. Vasodilatation by acetylcholine (0.03-3 microM) was significantly inhibited by L-NMMA (100 microM), whereas vasodilatation by adenosine (0.1-100 microM) or sodium nitroprusside (100 nM) was not affected. 4. The hyperaemic response after tenuissimus muscle contractions induced by motor nerve stimulation was unaffected by the presence of L-NMMA (100 microM). 5. Aggregates of platelets and white blood cells were seen in venules during superfusion with L-NMMA (100 microM), but not with D-NMMA (100 microM). 6. Our results suggest that endogenous NO formed from L-arginine is a modulator of microvascular tone and platelet and white cell-vessel wall interaction in vivo. Nitric oxide does not, however, appear to play a role in the mediation of functional hyperaemia in this tissue.

背景与目标： ：1。兔腱鞘肌微脉管系统的活体显微镜用于体内研究内源性一氧化氮（NO）在局部血管控制中的作用。局部应用精氨酸衍生物以调节由L-精氨酸形成NO的过程。 2. L-NG-单甲基精氨酸（L-NMMA）（10-100 microM），而不是D-NG-单甲基精氨酸（D-NMMA），剂量依赖性地降低了微血管直径。 L-NMMA（100 microM）诱导的血管收缩可通过用L-精氨酸（1 mM）预处理而不是D-精氨酸（1 mM）来预防。静脉内注射L-精氨酸（300 mg kg-1）可逆转L-NMMA（100 microM）的作用。本身以1 mM局部应用的L-精氨酸或D-精氨酸对微血管直径没有影响。 3. L-NMMA（100 microM）显着抑制了乙酰胆碱（0.03-3 microM）的血管舒张作用，而腺苷（0.1-100 microM）或硝普钠（100 nM）的血管舒张作用未受到影响。 4.运动神经刺激引起的腱鞘肌收缩后的充血反应不受L-NMMA（100 microM）的影响。 5.在与L-NMMA（100 microM）融合时，小静脉中可见血小板和白细胞的聚集，但与D-NMMA（100 microM）融合时未见。 6.我们的结果表明，由L-精氨酸形成的内源性NO是体内微血管张力和血小板与白细胞-血管壁相互作用的调节剂。然而，一氧化氮似乎在该组织的功能性充血的介导中不起作用。

BACKGROUND & AIMS: :Dendritic cells (DCs) are well known for their capacity to induce adaptive antitumor immune response through Ag presentation and tumor-specific T cell activation. Recent findings reveal that besides this role, DCs may display additional antitumor effects. In this study, we provide evidence that LPS- or IFN-gamma-activated rat bone marrow-derived dendritic cells (BMDCs) display killing properties against tumor cells. These cytotoxic BMDCs exhibit a mature DC phenotype, produce high amounts of IL-12, IL-6, and TNF-alpha, and retain their phagocytic properties. BMDC-mediated tumor cell killing requires cell-cell contact and depends on NO production, but not on perforin/granzyme or on death receptors. Furthermore, dead tumor cells do not exhibit characteristics of apoptosis. Thus, intratumoral LPS injections induce an increase of inducible NO synthase expression in tumor-infiltrating DCs associated with a significant arrest of tumor growth. Altogether, these results suggest that LPS-activated BMDCs represent powerful tumoricidal cells which enforce their potential as anticancer cellular vaccines.

背景与目标： 树突状细胞（DCs）以通过Ag呈递和肿瘤特异性T细胞活化而诱导适应性抗肿瘤免疫反应的能力而闻名。最近的发现表明，除这种作用外，DC可能还显示出额外的抗肿瘤作用。在这项研究中，我们提供的证据表明LPS或IFN-γ激活的大鼠骨髓源性树突状细胞（BMDC）表现出对肿瘤细胞的杀伤特性。这些细胞毒性BMDC表现出成熟的DC表型，产生大量的IL-12，IL-6和TNF-α，并保留其吞噬特性。 BMDC介导的肿瘤细胞杀伤需要细胞与细胞的接触，并取决于NO的产生，而不取决于穿孔素/粒酶或死亡受体。此外，死亡的肿瘤细胞不表现出凋亡特征。因此，肿瘤内LPS注射诱导与肿瘤生长的显着停滞相关的肿瘤浸润DC中诱导型NO合酶表达的增加。总而言之，这些结果表明，LPS激活的BMDC代表了强大的杀伤性细胞，可增强其作为抗癌细胞疫苗的潜力。

BACKGROUND & AIMS: :Soluble di-iron monooxygenases (SDIMOs) are key enzymes in the bacterial oxidation of hydrocarbons, and have applications in environmental and industrial biotechnology. SDIMOs from pure cultures are unlikely to represent the total diversity of this enzyme family, so we used polymerase chain reaction to survey the diversity of SDIMO alpha subunit genes in environmental samples, ethene enrichments and ethene-degrading bacterial isolates. From 178 cloned amplicons, 98 restriction fragment length polymorphism types were seen, from which 75 representative SDIMO sequences were obtained; 45 from environmental samples, 25 from enrichments and seven from isolates. The sequences were diverse, including genes similar to ethene (etnC), propene (amoC, pmoC), propane (prmA) and butane (bmoX) monooxygenases, in addition to many novel sequences comprising a new SDIMO group (group 6). Environmental samples showed the highest diversity, with strong representation of group 6 SDIMOs and prmA-like genes. Ethene stimulation of samples resulted in increased frequencies of group 4 SDIMOs (etnC-like). Four ethene-utilizing Mycobacterium isolates (NBB1-NBB4) from enrichments all contained etnC; one isolate (NBB4) also contained three additional SDIMO genes (bmoX-like, amoC-like and group 6). The primers, database, clone libraries and strains reported here provide a resource for future bioremediation and biocatalysis studies, with particular relevance for chlorinated alkene and alkane compounds.

背景与目标： ：可溶性二铁单加氧酶（SDIMOs）是烃类细菌氧化中的关键酶，并已应用于环境和工业生物技术中。来自纯培养物的SDIMO不太可能代表该酶家族的总多样性，因此我们使用聚合酶链反应来调查环境样品，乙烯富集和乙烯降解细菌分离物中SDIMOα亚基基因的多样性。从178个克隆的扩增子中，观察到98个限制性片段长度多态性类型，从中获得了75个代表性的SDIMO序列。来自环境样品的45个，来自浓缩物的25个和来自分离株的7个。这些序列是多种多样的，除了包括新的SDIMO组（第6组）的许多新颖序列外，还包括与乙烯（etnC），丙烯（amoC，pmoC），丙烷（prmA）和丁烷（bmoX）单加氧酶相似的基因。环境样品显示出最高的多样性，强烈代表了第6组SDIMOs和prmA样基因。乙烯对样品的刺激导致第4组SDIMO（etnC样）的频率增加。来自浓缩物中的四个利用乙烯的分枝杆菌分离株（NBB1-NBB4）均包含etnC；一个分离株（NBB4）还包含三个其他SDIMO基因（bmoX样，amoc样和第6组）。此处报道的引物，数据库，克隆文库和菌株为将来的生物修复和生物催化研究提供了资源，尤其与氯化烯烃和烷烃化合物有关。

BACKGROUND & AIMS: :Efferent innervation of the vestibular labyrinth is known to be cholinergic. More recent studies have also demonstrated the presence of the neuropeptide calcitonin gene-related peptide in this system. Nitric oxide is one of a new class of neurotransmitters, the gaseous transmitters. It acts as a second messenger and neurotransmitter in diverse physiological systems. We decided to investigate the anatomical distribution of the synthetic enzyme for nitric oxide, nitric oxide synthase (NOS), to clarify the role of nitric oxide in the vestibular periphery. NADPH diaphorase histochemical and NOS I immunohistochemical studies were done in the adult chinchilla and rat vestibular brainstem; diaphorase histochemistry was done in the chinchilla periphery. Retrograde tracing studies to verify the presence of NOS in brainstem efferent neurons were performed in young chinchillas. Our light microscopic results show that NOS I, as defined mainly by the presence of NADPH diaphorase, is present in a subpopulation of both brainstem efferent neurons and peripheral vestibular efferent boutons. Our ultrastructural results confirm these findings in the periphery. NADPH diaphorase is also present in a subpopulation of type I hair cells, suggesting that nitric oxide might be produced in and act locally upon these cells and other elements in the sensory epithelium. A hypothesis about how nitric oxide is produced in the vestibular periphery and how it may interact with other elements in the vestibular sensory apparatus is presented in the discussion.

背景与目标： ：已知前庭迷路的神经支配胆碱能。最近的研究也证明了该系统中神经肽降钙素基因相关肽的存在。一氧化氮是一类新的神经递质，即气态递质。它在各种生理系统中充当第二信使和神经递质。我们决定研究一氧化氮合成酶一氧化氮合酶（NOS）的解剖分布，以阐明一氧化氮在前庭周围的作用。在成年黄鼠和大鼠前庭脑干中进行了NADPH心肌黄递酶组织化学和NOS I免疫组化研究。心肌黄递酶的组织化学是在黄鼠的外周进行的。在年轻的龙猫中进行了逆行追踪研究，以验证脑干传出神经元中是否存在NOS。我们的光学显微镜结果显示，主要由NADPH心肌黄递酶的存在所定义的NOS I存在于脑干传出神经元和周围前庭传出的boutons的亚群中。我们的超微结构结果证实了这些发现。 NADPH心肌黄递酶也存在于I型毛细胞的亚群中，表明一氧化氮可能在这些细胞和感觉上皮中的其他元素上产生并局部作用。在讨论中提出了关于前庭周围如何产生一氧化氮以及它如何与前庭感觉装置中的其他元素相互作用的假设。

BACKGROUND & AIMS: :Multi-functional bilayer polymeric coatings are prepared with both controlled nitric oxide (NO) release and surface-bound active thrombomodulin (TM) alone or in combination with immobilized heparin. The outer-layer is made of CarboSil, a commercially available copolymer of silicone rubber (SR) and polyurethane (PU). The CarboSil is either carboxylated or aminated via an allophanate reaction with a diisocyanate compound followed by a urea-forming reaction between the generated isocyanate group of the polymer and the amine group of an amino acid (glycine), an oligopeptide (triglycine) or a diamine. The carboxylated CarboSil can then be used to immobilize TM through the formation of an amide bond between the surface carboxylic acid groups and the lysine residues of TM. Aminated CarboSil can also be employed to initially couple heparin to the surface, and then the carboxylic acid groups on heparin can be further used to anchor TM. Both surface-bound TM and heparin's activity are evaluated by chromogenic assays and found to be at clinically significant levels. The underlying NO release layer is made with another commercial SR-PU copolymer (PurSil) mixed with a lipophilic NO donor (N-diazeniumdiolated dibutylhexanediamine (DBHD/N(2)O(2))). The NO release rate can be tuned by changing the thickness of top coatings, and the duration of NO release at physiologically relevant levels can be as long as 2 weeks. The combination of controlled NO release as well as immobilized active TM and heparin from/on the same polymeric surface mimics the highly thromboresistant endothelium layer. Hence, such multifunctional polymer coatings should provide more blood-compatible surfaces for biomedical devices.

背景与目标： ：多功能双层聚合物涂料既可单独控制一氧化氮（NO）释放，又可与固定化肝素联合使用表面结合的活性血栓调节蛋白（TM）。外层由CarboSil制成，CarboSil是硅橡胶（SR）和聚氨酯（PU）的市售共聚物。 CarboSil通过与二异氰酸酯化合物的脲基甲酸酯反应被羧化或胺化，然后在聚合物的生成的异氰酸酯基团与氨基酸（甘氨酸），寡肽（三甘氨酸）或二胺的胺基之间形成脲形成反应。然后，可通过在表面羧酸基团与TM的赖氨酸残基之间形成酰胺键，将羧化的CarboSil固定在TM上。也可以使用胺化的CarboSil首先将肝素偶联至表面，然后可以进一步使用肝素上的羧酸基团来固定TM。表面结合的TM和肝素的活性均通过生色测定法进行评估，并发现在临床上具有显着水平。下层的NO释放层是由另一种商业SR-PU共聚物（PurSil）与亲油的NO供体（N-重氮二醇二丁基己二胺（DBHD / N（2）O（2）））混合制成的。可以通过改变表面涂层的厚度来调节NO的释放速率，并且在生理上相关的水平上，NO的释放持续时间可以长达2周。从同一聚合物表面上/上的受控NO释放以及固定化的活性TM和肝素的组合模拟了高度抗血栓形成的内皮层。因此，这种多功能聚合物涂层应为生物医学装置提供更多的血液相容性表面。

BACKGROUND & AIMS: :The transition metals iron (Fe) and copper (Cu) are needed at low levels for normal health and at higher levels they become toxic for humans and animals. The acute liver toxicity of Fe and Cu was studied in Sprague Dawley male rats (200 g) that received ip 0-60 mg/kg FeCl(2) or 0-30 mg/kg CuSO(4). Dose and time-responses were determined for spontaneous in situ liver chemiluminescence, phospholipid lipoperoxidation, protein oxidation and lipid soluble antioxidants. The doses linearly defined the tissue content of both metals. Liver chemiluminescence increased 4 times and 2 times after Fe and Cu overloads, with half maximal responses at contents (C(50%)) of 110 μgFe/g and 42 μgCu/g liver, and with half maximal time responses (t(1/2)) of 4h for both metals. Phospholipid peroxidation increased 4 and 1.8 times with C(50%) of 118 μg Fe/g and 45 μg Cu/g and with t(1/2) of 7h and 8h. Protein oxidation increased 1.6 times for Fe with C(50%) at 113 μg Fe/g and 1.2 times for Cu with 50 μg Cu/g and t(1/2) of 4h and 5h respectively. The accumulation of Fe and Cu in liver enhanced the rate of free radical reactions and produced oxidative damage. A similar free radical-mediated process, through the formation HO(•) and RO(•) by a Fenton-like homolytic scission of H(2)O(2) and ROOH, seems to operate as the chemical mechanism for the liver toxicity of both metals.

背景与目标： ：对于正常健康而言，过渡金属铁（Fe）和铜（Cu）的含量较低，而对人体和动物而言则具有较高的毒性。在接受ip 0-60 mg / kg FeCl（2）或0-30 mg / kg CuSO（4）的Sprague Dawley雄性大鼠（200 g）中研究了Fe和Cu的急性肝毒性。确定了自发性原位肝化学发光，磷脂脂质过氧化，蛋白质氧化和脂溶性抗氧化剂的剂量和时间响应。剂量线性地定义了两种金属的组织含量。 Fe和Cu超负荷后，肝化学发光增加4倍和2倍，在110μgFe/ g和42μgCu/ g肝含量（C（50％））处最大响应为一半，最大时间响应为一半（t（1 / 2））在4h内都适用于两种金属。磷脂过氧化增加4倍和1.8倍，其中C（50％）为118μgFe / g和45μgCu / g，t（1/2）为7h和8h。 Fe的蛋白质氧化在113μgFe / g的条件下含C（50％）的Fe增加1.6倍，Cu在50μgCu / g和t（1/2）分别为4h和5h的情况下增加1.2倍。肝脏中铁和铜的积累提高了自由基反应的速度并产生了氧化损伤。一个类似的自由基介导的过程，通过H（2）O（2）和ROOH的Fenton式同构分裂形成HO（•）和RO（•），似乎是肝脏毒性的化学机制两种金属。

BACKGROUND & AIMS: :The septic shock-induced decrease in mesenteric blood flow and release of proinflammatory cytokines are among the major pathophysiologic changes presumed to lead to multiple organ dysfunction syndrome (MODS). Increased nitric oxide (NO) levels are associated with both decreased mesenteric blood flow and positive modulation of proinflammatory cytokine release. In this study we aimed to determine the effect of the timing of the inhibition of nitric oxide synthase (NOS) on mesenteric blood flow and serum interleukin-10 (IL-10) concentrations during endotoxin shock. A nonspecific NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME), a specific NOS inhibitor aminoguanidine (AG), or placebo were injected 20 minutes before or 20 minutes after a lipopolysaccharide (LPS) or placebo challenge to Swiss-albino mice, as pretreatment or posttreatment, respectively. At 120 minutes after LPS or placebo injection the mesenteric blood flow was measured, and blood samples from the heart were obtained for IL-10 levels in both groups. Pretreatment and posttreatment with both NOS inhibitors prevented the LPS-induced decrease in mesenteric blood flow. Pretreatment was more effective for this purpose. Pretreatment accentuated the LPS-induced increase in serum IL-10 concentrations, whereas posttreatment had no significant effect. We conclude that the timing of NOS inhibition is important for attenuating some deleterious effects of endotoxin.

背景与目标： ：败血性休克引起的肠系膜血流量减少和促炎性细胞因子释放是导致多器官功能障碍综合症（MODS）的主要病理生理变化之一。一氧化氮（NO）水平升高与肠系膜血流量减少和促炎性细胞因子释放的正调节有关。在这项研究中，我们旨在确定内毒素休克期间一氧化氮合酶（NOS）抑制时机对肠系膜血流和血清白介素10（IL-10）浓度的影响。在脂多糖（LPS）或安慰剂攻击Swiss-20之前或之后20分钟注射非特异性NOS抑制剂NG-硝基-L-精氨酸甲酯（L-NAME），特异性NOS抑制剂氨基胍（AG）或安慰剂。白化病小鼠，分别作为预处理或后处理。在LPS或安慰剂注射后120分钟，测量肠系膜的血流，并从两组的心脏中获取血样中的IL-10水平。两种NOS抑制剂的预处理和后处理均防止了LPS诱导的肠系膜血流量的减少。为此目的，预处理更为有效。预处理加重了LPS诱导的血清IL-10浓度的增加，而后处理则无明显影响。我们得出结论，抑制NOS的时机对于减弱内毒素的某些有害作用很重要。

BACKGROUND & AIMS: :A bacterioferritin was recently isolated from the anaerobic sulphate-reducing bacterium Desulfivibrio desulfuricans ATCC 27774 [Romão et al. (2000) Biochemistry 39, 6841-6849]. Although its properties are in general similar to those of the other bacterioferritins, it contains a haem quite distinct from the haem B, found in bacterioferritins from aerobic organisms. Using visible and NMR spectroscopies, as well as mass spectrometry analysis, the haem is now unambiguously identified as iron-coproporphyrin III, the first example of such a prosthetic group in a biological system. This unexpected finding is discussed in the framework of haem biosynthetic pathways in anaerobes and particularly in sulphate-reducing bacteria.

背景与目标： ：最近从减少厌氧硫酸盐的细菌Desulfivibrio desulfuricans ATCC 27774中分离出一种细菌铁蛋白。 （2000）Biochemistry 39，6841-6849]。尽管其性质通常与其他细菌铁蛋白相似，但它所包含的血红素与好氧生物的细菌铁蛋白中发现的血红素B完全不同。使用可见光谱和NMR光谱以及质谱分析，血红素现在被明确鉴定为铁-卟啉III，这是生物系统中此类辅基的第一个实例。在厌氧菌，尤其是硫酸盐还原菌中的血红素生物合成途径的框架中讨论了这一出乎意料的发现。

BACKGROUND & AIMS: :Nitric oxide (NO) plays an important role in acute ischemic preconditioning (IPC). In addition to activating soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling pathways, NO-mediated protein S-nitros(yl)ation (SNO) has been recently shown to play an essential role in cardioprotection against ischemia-reperfusion (I/R) injury. In our previous studies, we have shown that IPC-induced cardioprotection could be blocked by treatment with either N-nitro-L-arginine methyl ester (L-NAME, a constitutive NO synthase inhibitor) or ascorbate (a reducing agent to decompose SNO). To clarify NO-mediated sGC/cGMP/PKG-dependent or -independent (i.e., SNO) signaling involved in IPC-induced cardioprotection, mouse hearts were Langendorff-perfused in the dark to prevent SNO decomposition by light exposure. Treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, a highly selective inhibitor of sGC) or KT5823 (a potent and selective inhibitor of PKG) did not abolish IPC-induced acute protection, suggesting that the sGC/cGMP/PKG signaling pathway does not play an important role in NO-mediated cardioprotective signaling during acute IPC. In addition, treatment with ODQ in IPC hearts provided an additional protective effect on functional recovery, in parallel with a higher SNO level in these ODQ+IPC hearts. In conclusion, these results suggest that the protective effect of NO is not related primarily to activation of the sGC/cGMP/PKG signaling pathway, but rather through SNO signaling in IPC-induced acute cardioprotection.

背景与目标： 一氧化氮（NO）在急性缺血预处理（IPC）中起重要作用。除了激活可溶性鸟苷基环化酶（sGC）/环鸟苷单磷酸（cGMP）/蛋白激酶G（PKG）信号传导途径外，最近还证明了NO介导的蛋白S-亚硝酰基（SNO）发挥着重要作用。对缺血再灌注（I / R）损伤的心脏保护作用。在我们以前的研究中，我们表明通过用N-硝基-L-精氨酸甲酯（L-NAME，组成型NO合酶抑制剂）或抗坏血酸（一种分解SNO的还原剂）治疗可以阻断IPC诱导的心脏保护。 。为了阐明与IPC诱导的心脏保护有关的NO介导的sGC / cGMP / PKG依赖性或非依赖性（即SN​​O）信号传导，在黑暗中对小鼠心脏进行Langendorff灌注，以防止SNO通过光照分解。用1H- [1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ，一种高度选择性的sGC抑制剂）或KT5823（一种有效且选择性的PKG抑制剂）治疗，不会废除IPC-诱导的急性保护，提示sGC / cGMP / PKG信号通路在急性IPC期间在NO介导的心脏保护信号中不发挥重要作用。此外，在这些ODQ IPC心脏中，用ODQ对IPC心脏进行治疗可对功能恢复提供额外的保护作用，同时具有更高的SNO水平。总之，这些结果表明，NO的保护作用主要与sGC / cGMP / PKG信号通路的激活无关，而是通过IPC诱导的急性心脏保护中的SNO信号进行。