• 【通过显微注射兴奋性氨基酸进一步介导中脑神经元介导猫的防御反应。】 复制标题 收藏 收藏
    DOI:10.1016/0304-3940(85)90261-7 复制DOI
    作者列表:Bandler R,Prineas S,McCulloch T
    BACKGROUND & AIMS: :Microinjections (0.05 microliter) of L-glutamic acid, L-aspartic acid and DL-homocysteic acid were made in the midbrain at the same sites from which a defence reaction had been elicited previously by electrical stimulation. It was found that injections made at sites within the midbrain periaqueductal grey region (PAG) consistently elicited the facio-vocal signs of the defence reaction, whereas injections made at sites in the tegmentum bordering the PAG did not. As injections of excitatory amino acids depolarize cell bodies but not axons, the results indicate that the midbrain PAG but not the adjacent tegmentum contains a population of neurones whose excitation elicits these reactions. Furthermore, the data suggested that such neurones may be located preferentially within the caudal half of the midbrain PAG.
    背景与目标: :在中脑的相同部位进行微量注射(0.05微升)的L-谷氨酸,L-天冬氨酸和DL-同型半胱氨酸,先前通过电刺激已引起防御反应。发现在中脑导水管周围灰色区域(PAG)内进行的注射始终会引起防御反应的面部声音迹象,而在与PAG相邻的睑板部位进行的注射则不然。随着注射兴奋性氨基酸使细胞体去极化而不是使轴突去极化,结果表明中脑PAG而不是相邻的盖骨包含了一群神经元,这些神经元的兴奋引发了这些反应。此外,数据表明此类神经元可能优先位于中脑PAG的尾半部。
  • 【豆浆抑制胆固醇诱导的炎症基因表达,并改善SD大鼠皮肤中的脂肪酸谱。】 复制标题 收藏 收藏
    DOI:10.1016/j.bbrc.2012.10.074 复制DOI
    作者列表:Lee SM,Kim Y,Choi Hj,Choi J,Yi Y,Yoon S
    BACKGROUND & AIMS: :Recently, an elevation in skin cholesterol level has been implicated in skin inflammation. Given the potential therapeutic effects of soy on low grade inflammatory diseases, we hypothesized that a CHOL diet could promote an inflammatory response in skin and that soy milk (SM) or fermented soy milk (F.SM) could prevent this cholesterol-induced skin inflammation. To test this hypothesis, freeze-dried SM or F.SM was provided as a protein replacement for 20% of the casein in the diets of Sprague-Dawley (SD) rats. The animals were divided into the following groups: (1) control group (CTRL), AIN76A diet without cholesterol, (2) high cholesterol (CHOL) group, AIN76A with 1% (w/w) cholesterol, (3) SM group, CHOL diet with freeze-dried SM, and (4) F.SM group, CHOL diet with F.SM. In the CHOL group, the expression levels of pro-inflammatory genes, including IL-1β, IL-1α, iNOS, and COX-2, were elevated. In comparison, the SM and F.SM groups displayed the lowered expression of IL-1β, COX-2, F4/80, and Cd68, an increase of a n-3/n-6 ratio, and a reduction in the estimated desaturase activities of delta 5 desaturase (D5D) and steaoryl CoA desaturase (SCD-1). In particular, F.SM significantly increased the proportion of dihomo-γ-linolenic acid (DGLA) in skin fatty acid (FA) composition compared with the CHOL group. Here we present evidence that SM or F.SM could alleviate the inflammatory response in the skin that is triggered by excess dietary cholesterol by reducing the expression of pro-inflammatory genes. This response could be partly associated with a decreased in macrophages in skin and/or by modulation of the skin's FA composition.
    背景与目标: :最近,皮肤胆固醇水平升高与皮肤炎症有关。考虑到大豆对低度炎症性疾病的潜在治疗作用,我们假设CHOL饮食可以促进皮肤中的炎症反应,而豆浆(SM)或发酵豆浆(F.SM)可以预防这种胆固醇诱导的皮肤炎症。为了检验这一假设,提供了冷冻干燥的SM或F.SM作为Sprague-Dawley(SD)大鼠饮食中20%酪蛋白的蛋白质替代品。将动物分为以下几组:(1)对照组(CTRL),不含胆固醇的AIN76A饮食,(2)高胆固醇(CHOL)组,含1%(w / w)胆固醇的AIN76A,(3)SM组,冻干SM的CHOL饮食,和(4)F.SM组,F.SM的CHOL饮食。在CHOL组中,促炎基因包括IL-1β,IL-1α,iNOS和COX-2的表达水平升高。相比之下,SM和F.SM组显示出IL-1β,COX-2,F4 / 80和Cd68的表达降低,n-3 / n-6比例增加以及估计的去饱和酶降低δ5去饱和酶(D5D)和硬脂酰CoA去饱和酶(SCD-1)的活性。特别是,与CHOL组相比,F.SM显着增加了皮肤脂肪酸(FA)组合物中二高-γ-亚麻酸(DGLA)的比例。在这里,我们提供的证据表明,SM或F.SM可以通过减少促炎基因的表达来缓解皮肤中由过量饮食胆固醇触发的炎症反应。该反应可能部分与皮肤巨噬细胞减少和/或通过调节皮肤的FA成分有关。
  • 【线粒体转化和脂肪酸去饱和之间的泛素依赖性平衡调节线粒体融合。】 复制标题 收藏 收藏
    DOI:10.1038/ncomms15832 复制DOI
    作者列表:Cavellini L,Meurisse J,Findinier J,Erpapazoglou Z,Belgareh-Touzé N,Weissman AM,Cohen MM
    BACKGROUND & AIMS: :Mitochondrial integrity relies on homotypic fusion between adjacent outer membranes, which is mediated by large GTPases called mitofusins. The regulation of this process remains nonetheless elusive. Here, we report a crosstalk between the ubiquitin protease Ubp2 and the ubiquitin ligases Mdm30 and Rsp5 that modulates mitochondrial fusion. Ubp2 is an antagonist of Rsp5, which promotes synthesis of the fatty acids desaturase Ole1. We show that Ubp2 also counteracts Mdm30-mediated turnover of the yeast mitofusin Fzo1 and that Mdm30 targets Ubp2 for degradation thereby inducing Rsp5-mediated desaturation of fatty acids. Exogenous desaturated fatty acids inhibit Ubp2 degradation resulting in higher levels of Fzo1 and maintenance of efficient mitochondrial fusion. Our results demonstrate that the Mdm30-Ubp2-Rsp5 crosstalk regulates mitochondrial fusion by coordinating an intricate balance between Fzo1 turnover and the status of fatty acids saturation. This pathway may link outer membrane fusion to lipids homeostasis.
    背景与目标: 线粒体的完整性依赖于相邻外膜之间的同型融合,这种融合是由称为线粒体融合蛋白的大型GTP酶介导的。尽管如此,对这一过程的规制仍然难以捉摸。在这里,我们报道了泛素蛋白酶Ubp2与泛素连接酶Mdm30和Rsp5之间的串扰,该串扰调节线粒体融合。 Ubp2是Rsp5的拮抗剂,可促进脂肪酸去饱和酶Ole1的合成。我们表明,Ubp2还抵消了酵母Mofmin Fzo1的Mdm30介导的营业额,并且Mdm30靶向Ubp2降解,从而诱导了Rsp5介导的脂肪酸去饱和。外源性不饱和脂肪酸抑制Ubp2降解,导致Fzo1含量更高,并维持有效的线粒体融合。我们的结果表明,Mdm30-Ubp2-Rsp5串扰通过协调Fzo1周转率与脂肪酸饱和状态之间的复杂平衡来调节线粒体融合。该途径可能将外膜融合与脂质稳态联系起来。
  • 【1期或更高阶段的脂肪浸润显着损害了棘上修复的长期愈合。】 复制标题 收藏 收藏
    DOI:10.1016/j.jse.2017.03.024 复制DOI
    作者列表:Godenèche A,Elia F,Kempf JF,Nich C,Berhouet J,Saffarini M,Collin P,SOFCOT.
    BACKGROUND & AIMS: BACKGROUND:Fatty infiltration (FI) compromises outcomes of rotator cuff repairs. Most clinicians consider FI of the infraspinatus, whether it is torn or intact, because it is most rapidly affected. The purpose of this study was to report long-term outcomes of isolated supraspinatus repairs and to determine their associations with FI of the infraspinatus and supraspinatus. METHODS:The records of 182 patients who underwent repair of isolated supraspinatus tears and had preoperative magnetic resonance imaging were retrieved. Of these, 147 patients were evaluated at 10 years' follow-up using the Constant score and magnetic resonance imaging scans. RESULTS:Preoperative FI was greater in the supraspinatus (52% stage ≥1) than in the infraspinatus (29% stage ≥1). The 10-year Constant scores were influenced by FI of the supraspinatus (P = .006) but not of the infraspinatus (P = .422). Multivariable regression confirmed that Constant scores were significantly lower for female patients, repetitive work, and stage 1 and stage 2 FI of the supraspinatus in addition to open surgery. Retear rates (Sugaya types IV-V) were also influenced by FI of the supraspinatus (P = .001) but not of the infraspinatus (P = .979). Shoulders with supraspinatus FI at stages 0, 1, and 2 had retear rates of 10%, 22%, and 31%, respectively. Multivariable regression affirmed that the odds of retears are significantly increased by both stage 1 and stage 2 FI of the supraspinatus. CONCLUSIONS:The Constant scores and retear rates were significantly associated with FI of the torn supraspinatus (stage ≥1) but not of the intact infraspinatus. The authors recommend that rapid surgical intervention be considered, before accumulation of fat, especially for young, active patients.
    背景与目标: 背景:脂肪浸润(FI)损害了肩袖修复的效果。大多数临床医生都考虑到下鼻窦的FI,无论其是撕裂的还是完整的,因为它受到的影响最为迅速。这项研究的目的是报告孤立的上棘修复的长期结果,并确定它们与下脊柱和上棘的FI的关系。
    方法:检索182例行孤立性上睑上睑裂孔修复并术前进行磁共振成像的患者的病历。在其中的147位患者中,使用Constant评分和磁共振成像扫描在10年的随访中对其进行了评估。
    结果:术前FI在棘上肌(52%≥1)大于在鼻下肌(29%≥1)。 10年常数评分受脊柱上方FI的影响(P = .006),但不影响椎下肌的FI(P = .422)。多变量回归证实,除开放手术外,女性患者,重复性工作以及棘上肌第1期和第2期FI的恒定评分明显更低。退缩率(Sugaya IV-V型)也受棘上肌FI的影响(P = .001),而不受鞘下肌FI的影响(P = .979)。棘上棘FI在0、1和2期的肩后退率分别为10%,22%和31%。多变量回归证实,上棘的第1阶段和第2阶段FI均使后遗几率显着增加。
    结论:恒定评分和后退率与棘上棘(≥1期)的FI显着相关,而与完整的鼻下肌无关。作者建议在脂肪积聚之前考虑快速外科手术干预,尤其是对于年轻活跃的患者。
  • 【GFT投影NMR可有效鉴定核酸中的(1)H /(13)C糖自旋系统。】 复制标题 收藏 收藏
    DOI:10.1007/s10858-012-9687-5 复制DOI
    作者列表:Atreya HS,Sathyamoorthy B,Jaipuria G,Beaumont V,Varani G,Szyperski T
    BACKGROUND & AIMS: :A newly implemented G-matrix Fourier transform (GFT) (4,3)D HC(C)CH experiment is presented in conjunction with (4,3)D HCCH to efficiently identify (1)H/(13)C sugar spin systems in (13)C labeled nucleic acids. This experiment enables rapid collection of highly resolved relay 4D HC(C)CH spectral information, that is, shift correlations of (13)C-(1)H groups separated by two carbon bonds. For RNA, (4,3)D HC(C)CH takes advantage of the comparably favorable 1'- and 3'-CH signal dispersion for complete spin system identification including 5'-CH. The (4,3)D HC(C)CH/HCCH based strategy is exemplified for the 30-nucleotide 3'-untranslated region of the pre-mRNA of human U1A protein.
    背景与目标: :结合(4,3)D HCCH提出了新实施的G-矩阵傅里叶变换(GFT)(4,3)D HC(C)CH实验,以有效识别(1)H /(13)C糖自旋(13)C标记核酸中的系统。该实验能够快速收集高度解析的中继4D HC(C)CH光谱信息,即由两个碳键分隔的(13)C-(1)H基团的位移相关性。对于RNA,(4,3)D HC(C)CH利用相对有利的1'-和3'-CH信号分散度来完全识别包括5'-CH的自旋系统。基于(4,3)D HC(C)CH / HCCH的策略以人U1A蛋白前mRNA的30个核苷酸的3'非翻译区为例。
  • 【模型膜I中的荧光探针:二棕榈酰磷脂酰胆碱的单层和脂质体中的蒽酰基脂肪酸衍生物。】 复制标题 收藏 收藏
    DOI:10.1021/bi00643a034 复制DOI
    作者列表:Cadenhead DA,Kellner BM,Jacobson K,Papahadjopoulos D
    BACKGROUND & AIMS: A study of three fluorescent anthroyl probes has been carried out using pure and mixed monomolecular films with dipalmitoylphosphatidylcholine. In addition, fluorescence depolarization and differential scanning calorimetry data were obtained from dipalmitoylphosphatidylcholine vesicles with incorporated anthroyl probes. The three probes used were 2-(9-anthroyl)palmitic acid. 12-(9-anthroyl)stearic acid, and 16-(9-anthroyl)palmitic acid. The latter probe was synthesized for these studies. In monolayers the probes shifted the onset of the liquid-condensed/liquid-expanded monolayer phase transition with the extent of the shift decreasing in the order2-(9-anthroyl)palmitic acid greater than 12-(9-anthroyl)stearic acid greater than 16-(9-anthroyl)stearic acid. A corresponding decrease in the gel-liquid crystalline bilayer transition temperature (Tc) showed the same order of perturbation in both the fluorescence depolarization and differential scanning calorimetry data. Locating the anthroyl entity in the center of the bilayer would appear to provide a minimum perturbation.

    背景与目标: 使用带有二棕榈酰磷脂酰胆碱的纯的和混合的单分子膜对三种荧光蒽基探针进行了研究。此外,荧光二极化和差示扫描量热法数据是从二棕榈酰磷脂酰胆碱囊泡中掺入蒽酰基探针获得的。使用的三个探针是2-(9-蒽基)棕榈酸。 12-(9-蒽基)硬脂酸和16-(9-蒽基)棕榈酸。合成了后一种探针用于这些研究。在单层中,探针使液体缩合/液体膨胀的单层相变的开始发生位移,其移位程度以2-(9-蒽基)棕榈酸大于12-(9-蒽基)硬脂酸大于16-(9-蒽基)硬脂酸。凝胶-液晶双层转变温度(Tc)的相应降低在荧光去极化和差示扫描量热数据中都显示出相同程度的扰动。将蒽基实体位于双层的中心似乎可以提供最小的扰动。

  • 【脂肪酸氢过氧化物对解脂耶氏酵母的毒性:其膜流化作用的含义。】 复制标题 收藏 收藏
    DOI:10.1016/j.bbamem.2007.05.016 复制DOI
    作者列表:Tran Thanh H,Beney L,Simonin H,Nguyen TX,Gervais P,Belin JM,Husson F
    BACKGROUND & AIMS: :Linoleic acid hydroperoxide (HPOD), substrate of hydroperoxide lyase, an enzyme of the lipoxygenase pathway, can be transformed into many aromatic compounds, the so-called "green notes". The presence of linoleic acid hydroperoxide in the culture medium of Yarrowia lipolytica, the yeast expressing the cloned hydroperoxide lyase of green bell pepper, undoubtedly exerted an inhibition on the growth and a toxic effect with 90% of yeast cells died after 120 min of exposition in 100 mM HPOD solution. The increase in cell membrane fluidity evaluated by measuring fluorescence generalized polarization with the increasing concentration of HPOD in the medium confirmed the fluidizing action of HPOD on yeast membrane. In addition, we determined by infrared spectroscopy measurement that this compound rapidly diffused into model phospholipids [1, 2-Dimyristoyl-D54-sn-Glycero-3-Phosphocholine (DMPC-D54)] bilayer, modifying their general physical state and their phase transition. In the presence of various concentrations of HPOD, the phase transition of DMPC-D54 occurred with an increase of both the corresponding wave number shift and the temperature range but the phase transition temperature was not modified. These results show that the toxic effects of HPOD on the yeast Yarrowia lipolytica may be initially linked to a strong interaction of this compound with the cell membrane phospholipids and components.
    背景与目标: :亚油酸氢过氧化物(HPOD),氢过氧化物裂解酶的底物,脂氧合酶途径的一种酶,可以转化为许多芳香族化合物,即所谓的“绿色香精”。表达克隆的青椒的氢氧化酵母的酵母耶氏酵母(Yarrowia lipolytica)培养基中亚油酸氢过氧化物的存在无疑对生长产生抑制作用,90%的酵母细胞在暴露120min后死亡的毒性作用。 100 mM HPOD解决方案。通过测量荧光广义极化随培养基中HPOD浓度的增加而评估的细胞膜流动性的增加证实了HPOD在酵母膜上的流化作用。此外,我们通过红外光谱测量确定该化合物迅速扩散到模型磷脂[1,2-Dimyristoyl-D54-sn-Glycero-3-Phosphocholine(DMPC-D54)]双层中,从而改变了它们的一般物理状态和相变。在各种浓度的HPOD存在下,DMPC-D54的相变会随着相应波数偏移和温度范围的增加而发生,但相变温度没有改变。这些结果表明,HPOD对酵母解脂耶氏酵母的毒性作用可能最初与该化合物与细胞膜磷脂和组分的强相互作用有关。
  • 【小鼠中脂肪酸结合蛋白的缺乏赋予了对实验性自身免疫性脑脊髓炎发展的保护。】 复制标题 收藏 收藏
    DOI:10.4049/jimmunol.179.1.313 复制DOI
    作者列表:Reynolds JM,Liu Q,Brittingham KC,Liu Y,Gruenthal M,Gorgun CZ,Hotamisligil GS,Stout RD,Suttles J
    BACKGROUND & AIMS: :Fatty acid-binding proteins (FABPs) act as intracellular receptors for a variety of hydrophobic compounds, enabling their diffusion within the cytoplasmic compartment. Recent studies have demonstrated the ability of FABPs to simultaneously regulate metabolic and inflammatory pathways. We investigated the role of adipocyte FABP and epithelial FABP in the development of experimental autoimmune encephalomyelitis to test the hypothesis that these FABPs impact adaptive immune responses and contribute to the pathogenesis of autoimmune disease. FABP-deficient mice exhibited a lower incidence of disease, reduced clinical symptoms of experimental autoimmune encephalomyelitis and dramatically lower levels of proinflammatory cytokine mRNA expression in CNS tissue as compared with wild-type mice. In vitro Ag recall responses of myelin oligodendrocyte glycoprotein 35-55-immunized FABP(-/-) mice showed reduced proliferation and impaired IFN-gamma production. Dendritic cells deficient for FABPs were found to be poor producers of proinflammatory cytokines and Ag presentation by FABP(-/-) dendritic cells did not promote proinflammatory T cell responses. This study reveals that metabolic-inflammatory pathway cross-regulation by FABPs contributes to adaptive immune responses and subsequent autoimmune inflammation.
    背景与目标: :脂肪酸结合蛋白(FABP)充当多种疏水化合物的细胞内受体,使其在细胞质区室中扩散。最近的研究表明FABP同时调节代谢和炎症途径的能力。我们调查了脂肪细胞FABP和上皮FABP在实验性自身免疫性脑脊髓炎的发展中的作用,以检验以下假设:这些FABP影响适应性免疫反应并有助于自身免疫性疾病的发病机理。与野生型小鼠相比,FABP缺陷型小鼠表现出较低的疾病发病率,减少了实验性自身免疫性脑脊髓炎的临床症状,并且在CNS组织中的促炎细胞因子mRNA表达水平大大降低。髓鞘少突胶质细胞糖蛋白35-55免疫的FABP(-/-)小鼠的体外Ag召回反应显示出增殖减少和IFN-γ产生受损。发现缺乏FABP的树突状细胞是促炎性细胞因子的不良生产者,并且FABP(-/-)树突状细胞的Ag呈递并不促进促炎性T细胞应答。这项研究表明,FABPs对代谢-炎症途径的交叉调节有助于适应性免疫反应和随后的自身免疫炎症。
  • 【长寿侏儒小鼠:胆汁酸是长寿信号吗?】 复制标题 收藏 收藏
    DOI:10.1111/j.1474-9726.2007.00309.x 复制DOI
    作者列表:Gems D
    BACKGROUND & AIMS: :Pathways that control aging act via regulated biochemical processes, among which metabolism of xenobiotics (potentially harmful chemical agents encountered as environmental toxicants, for example, drugs, or produced internally) is one possible candidate. A new study of long-lived Ghrhr mutant mice reports that increased bile acid levels activate xenobiotic metabolism via the nuclear receptor, farnesoid X receptor. This increases resistance to xenobiotic stress, possibly contributing to longevity.
    背景与目标: :控制衰老的途径是通过受控的生化过程起作用的,其中异生素(作为环境毒物遇到的潜在有害化学剂,例如药物或内部产生)的代谢可能是一种候选方法。一项针对长寿Ghrhr突变小鼠的新研究报告,胆汁酸水平升高会通过核受体,法呢素X受体激活异种生物代谢。这增加了对异种生物胁迫的抵抗力,可能有助于延长寿命。
  • 【脂肪酸氧化途径作为胰岛素抵抗的治疗靶标。】 复制标题 收藏 收藏
    DOI:10.1517/14728222.10.5.749 复制DOI
    作者列表:Clapham JC,Storlien LH
    BACKGROUND & AIMS: :It is recognised that obesity is a major driver for insulin resistance and Type 2 diabetes in both adult and young members of diverse societies. Weight loss strategies involving diet, exercise and behaviour modification work only for the minority of highly motivated individuals, but fail completely in the vast majority; yet weight loss is associated with benefits in metabolic health. Why is it so difficult to maintain weight loss in the longer term? Here, the authors explore the possibility that energy partitioning, especially of lipids, plays a key role in both weight recidivism and, by association, insulin resistance. Drug targets that address key pathways important in this process, where progress in drug discovery is apparent, are discussed.
    背景与目标: :众所周知,肥胖是各种社会的成年和年轻成员中胰岛素抵抗和2型糖尿病的主要驱动力。涉及饮食,运动和行为改变的减肥策略仅对少数积极进取的人有效,但在绝大多数人中完全无效;减肥与代谢健康有关。为什么长期保持减肥如此困难?在这里,作者探索了能量分配(尤其是脂质)在体重减轻和胰岛素抵抗中起关键作用的可能性。讨论了解决在此过程中很重要的关键途径的药物靶标,在该过程中,药物发现有了明显的进展。
  • 【不同有机酸对头孢泊肟普罗西汀速释片溶解性增强的影响及其稳定性研究。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Jabeen S,Hassan F,Yousuf RI,Shoaib MH,Israr F,Hasan SMF,Saeed R,Farooqi S
    BACKGROUND & AIMS: :Cefpodoxime proxetil is a third generation cephalosporin antibiotic demonstrates pH dependent solubility and is highly soluble only in acidic pH. The purpose of this investigation was to design and develop immediate release tablets of cefpodoxime proxetil by direct compression method and determine the effect of different solid buffers (organic acids) such as fumaric acid (formulations F1-F4), maleic acid (formulations M1-M4) and citric acid (formulations C1-C4) by using cefpodoxime and acid in the ratios of 4:1, 2:1, 1:1 and 1:2 to achieve pH-independent release of the drug. Physical parameters and assay were found to be within the acceptable range as prescribed in USP 36 / NF 31. In vitro dissolution studies of each formulation were performed in distilled water, USP dissolution medium, HCl buffer solution of pH 1.2, phosphate buffer solutions of pH 4.5 and 6.8 to observe the drug release. The formulations F3, F4, M4 were selected for film coating on the basis of better drug release profile, to protect the drug from chemical degradation through hydrolysis. Film coated formulation F3, F4 and M4 showed a remarkable in vitro release of the drug (72.88±0.43 to 92.67±0.71%) within 30min of observation in all dissolution media and further evaluated by model independent and model dependent approaches. The drug release was found to be best fit to Weibull model as highest r2adjusted (0.924-0.998) and lowest AIC (18.416-54.710) values were obtained in all dissolution media. R Gui® applied for stability studies of F3 and F4 formulations, showing shelf lives of 28 & 27months at ambient and 33 months at accelerated temperatures. Formulation F4 was chosen as best formulation on the basis of physical properties, highest dissolution rate and stability studies.
    背景与目标: :头孢泊肟酯是第三代头孢菌素抗生素,显示出pH依赖性溶解度,仅在酸性pH值下高度可溶。这项研究的目的是通过直接压缩方法设计和开发头孢泊肟肟酯的速释片,并确定不同的固体缓冲剂(有机酸)如富马酸(配方F1-F4),马来酸(配方M1-M4)的作用。 )和柠檬酸(配方C1-C4),使用头孢泊肟和酸的比例为4:1、2:1、1:1和1:2,以实现不依赖pH值的药物释放。发现物理参数和测定均在USP 36 / NF 31规定的可接受范围内。每种制剂的体外溶出度研究是在蒸馏水,USP溶出介质,pH 1.2的HCl缓冲溶液,pH 1.2的磷酸盐缓冲溶液中进行的。 4.5和6.8观察药物释放情况。基于更好的药物释放曲线,选择制剂F3,F4,M4进行薄膜包衣,以保护药物免受水解的化学降解。薄膜包衣的制剂F3,F4和M4在观察到的30分钟内在所有溶出介质中均显示出显着的药物体外释放(72.88±0.43至92.67±0.71%),并通过模型独立和模型依赖的方法进行了进一步评估。发现在所有溶出介质中均获得了最高的r2调整值(0.924-0.998)和最低的AIC值(18.416-54.710),从而使药物释放最适合于Weibull模型。 RGui®应用于F3和F4配方的稳定性研究,在环境温度下的货架期为28和27个月,在加速温度下的货架期为33个月。根据物理性能,最高的溶出速率和稳定性研究,选择配方F4作为最佳配方。
  • 【欧洲鲈鱼(Dicentrarchus labrax)中的脂肪酸代谢:鱼油替代饮食中n-6 PUFA和MUFA的影响。】 复制标题 收藏 收藏
    DOI:10.1007/s10695-012-9753-7 复制DOI
    作者列表:Eroldoğan TO,Yılmaz AH,Turchini GM,Arslan M,Sirkecioğlu NA,Engin K,Özşahinoğlu I,Mumoğullarında P
    BACKGROUND & AIMS: :Monounsaturated fatty acids (MUFA)-rich and n-6 polyunsaturated fatty acid (n-6 PUFA)-rich vegetable oils are increasingly used as fish oil replacers for aquafeed formulation. The present study investigated the fatty acid metabolism in juvenile European sea bass (Dicentrarchus labrax, 38.4 g) fed diets containing fish oil (FO, as the control treatment) or two different vegetable oils (the MUFA-rich canola/rapeseed oil, CO; and the n-6 PUFA-rich cottonseed oil, CSO) tested individually or as a 50/50 blend (CO/CSO). The whole-body fatty acid balance method was used to deduce the apparent in vivo fatty acid metabolism. No effect on growth performance and feed utilization was recorded. However, it should be noted that the fish meal content of the experimental diets was relatively high, and thus the requirement for n-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA) may have likely been fulfilled even if dietary fish oil was fully replaced by vegetable oils. Overall, relatively little apparent in vivo fatty acid bioconversion was recorded, whilst the apparent in vivo β-oxidation of dietary fatty acid was largely affected by the dietary lipid source, with higher rate of β-oxidation for those fatty acids which were provided in dietary surplus. The deposition of 20:5n-3 and 22:6n-3, as % of the dietary intake, was greatest for the fish fed on the CSO diet. It has been shown that European sea bass seems to be able to efficiently use n-6 PUFA for energy substrate, and this may help in minimizing the β-oxidation of the health benefiting n-3 LC-PUFA and thus increase their deposition into fish tissues.
    背景与目标: :富含不饱和脂肪酸(MUFA)和富含n-6多不饱和脂肪酸(n-6 PUFA)的植物油越来越多地用作水产饲料配方的鱼油替代品。本研究调查了以鱼油(FO作为对照)或两种不同的植物油(富含MUFA的低芥酸菜籽油/菜籽油​​CO)喂养的日粮欧洲鲈鱼(Dicentrarchus labrax,38.4 g)的脂肪酸代谢。以及分别或以50/50的混合物(CO / CSO)进行测试的n-6富含PUFA的棉籽油(CSO)。全身脂肪酸平衡法用于推导体内明显的脂肪酸代谢。没有记录到对生长性能和饲料利用率的影响。但是,应注意的是,实验饮食中鱼粉含量较高,因此即使食用鱼,也可能满足n-3长链多不饱和脂肪酸(n-3 LC-PUFA)的要求。油被植物油完全替代。总的来说,记录的体内脂肪酸的明显表观生物转化相对较少,而膳食脂肪酸的表观体内β-氧化作用很大程度上受膳食脂质来源的影响,膳食中提供的那些脂肪酸的β-氧化率较高。剩余。以日粮摄入量的百分比计,20:5n-3和22:6n-3的沉积量对以CSO日粮喂养的鱼类最大。研究表明,欧洲鲈鱼似乎能够有效地将n-6 PUFA用作能量底物,这可能有助于将有益于健康的n-3 LC-PUFA的β-氧化作用降至最低,从而增加其在鱼类中的沉积组织。
  • 【靶向脂肪酸酰胺水解酶(FAAH)和瞬时受体电位(TRP)通道的四氢-β-咔啉衍生物。】 复制标题 收藏 收藏
    DOI:10.1016/j.bmcl.2012.10.137 复制DOI
    作者列表:Ortar G,De Petrocellis L,Moriello AS,Allarà M,Morera E,Nalli M,Di Marzo V
    BACKGROUND & AIMS: :A series of twenty-five derivatives of tetrahydro-β-carbolines 1-3 was synthesized and assayed on FAAH and TRPV1 and TRPA1 channels. Four carbamates, that is, 5a,c,e, and 9b inhibited FAAH with significant potency and interacted also effectively with TRPV1 and TRPA1 nociceptive receptors, while ureas 7b,d,f, and 8a,b were endowed with specific submicromolar TRPV1 modulating activities.
    背景与目标: :合成了一系列的二十五个四氢-β-咔啉1-3衍生物,并在FAAH和TRPV1和TRPA1通道上进行了测定。四种氨基甲酸酯5a,c,e和9b显着抑制FAAH,并且还与TRPV1和TRPA1伤害感受器有效相互作用,而尿素7b,d,f和8a,b具有特定的亚微摩尔TRPV1调节活性。 。
  • 【通过近端小管中的肝型脂肪酸结合蛋白改善血管紧张素II诱导的盐敏感性高血压。】 复制标题 收藏 收藏
    DOI:10.1161/HYPERTENSIONAHA.113.01203 复制DOI
    作者列表:Osaki K,Suzuki Y,Sugaya T,Tanifuji C,Nishiyama A,Horikoshi S,Tomino Y
    BACKGROUND & AIMS: :Inappropriate activation of the intrarenal renin-angiotensin system induces generation of reactive oxygen species and tubulointerstitial inflammation, which contribute to salt-sensitive hypertension (SSHT). Liver-type fatty acid-binding protein is expressed in proximal tubules in humans, but not in rodents, and may play an endogenous antioxidative role. The objective of the present study was to examine the antioxidative effect of liver-type fatty acid-binding protein on post-angiotensin II SSHT model in transgenic mice with selective overexpression of human liver-type fatty acid-binding protein in the proximal tubules. The transgenic mice showed marked protection against angiotensin II-induced SSHT. Overexpression of tubular liver-type fatty acid-binding protein prevented intrarenal T-cell infiltration and also reduced reactive oxygen species generation, intrarenal renin-angiotensin system activation, and monocyte chemotactic protein-1 expression. We also performed an in vitro study using the murine proximal tubular cell lines with or without recombinant liver-type fatty acid-binding protein and murine proximal tubular cell lines transfected with human liver-type fatty acid-binding protein, and found that gene transfection of liver-type fatty acid-binding protein and, in part, recombinant liver-type fatty acid-binding protein administration had significantly attenuated angiotensin II-induced reactive oxygen species generation and the expression of angiotensinogen and monocyte chemotactic protein-1 in murine proximal tubular cell lines. These findings indicated that liver-type fatty acid-binding protein in the proximal tubules may protect against angiotensin II-induced SSHT by attenuating activation of the intrarenal renin-angiotensin system and reducing oxidative stress and tubulointerstitial inflammation. Present data suggest that liver-type fatty acid-binding protein in the proximal tubules may be a novel therapeutic target for SSHT.
    背景与目标: :肾内肾素-血管紧张素系统的不适当活化会诱导活性氧的产生和肾小管间质发炎,从而导致盐敏感性高血压(SSHT)。肝型脂肪酸结合蛋白在人的近端小管中表达,但在啮齿动物中不表达,并且可能起内源性抗氧化作用。本研究的目的是研究在邻近小管中选择性表达人肝型脂肪酸结合蛋白的转基因小鼠中,肝型脂肪酸结合蛋白对血管紧张素Ⅱ后SSHT模型的抗氧化作用。转基因小鼠对血管紧张素II诱导的SSHT具有明显的保护作用。肾小管型脂肪酸结合蛋白的过度表达阻止了肾内T细胞的浸润,并减少了活性氧的产生,肾内肾素-血管紧张素系统的活化以及单核细胞趋化蛋白1的表达。我们还使用有或没有重组肝型脂肪酸结合蛋白的鼠近端肾小管细胞系以及用人肝型脂肪酸结合蛋白转染的鼠近端肾小管细胞系进行了体外研究,发现肝型脂肪酸结合蛋白,以及部分重组肝型脂肪酸结合蛋白的给药,显着减弱了血管紧张素II诱导的活性氧的产生以及鼠近端肾小管细胞中血管紧张素原和单核细胞趋化蛋白1的表达线。这些发现表明,近端小管中的肝型脂肪酸结合蛋白可通过减弱肾内肾素-血管紧张素系统的激活并减少氧化应激和肾小管间质炎症来预防血管紧张素II诱导的SSHT。目前的数据表明,近端肾小管中的肝型脂肪酸结合蛋白可能是SSHT的新型治疗靶标。
  • 【排尿利尿剂的研究。 I.黄嘌呤氧基氧乙酸和二氢呋喃蒽酮-2-羧酸的合成和活性。】 复制标题 收藏 收藏
    DOI:10.1248/cpb.38.1266 复制DOI
    作者列表:Sato H,Dan T,Onuma E,Tanaka H,Koga H
    BACKGROUND & AIMS: :A series of substituted xanthonyloxyacetic acids (5 and 6), 1,2-dihydrofuro[2,3-c]xanthone-2-carboxylic acids (7) and 2,3-dihydrofuro[3,2-b]xanthone-2-carboxylic acids (8) were synthesized and tested for diuretic and uricosuric activities in rats. Most of the xanthon-3-yloxyacetic acids (5) and 7 showed potent diuretic activities, while 8 had lower activities. Uricosuric activities were found in 5c, 5f, 5k, 5m, 5o, 5p, 5r, 7m, 7p and 8q.
    背景与目标: :一系列取代的氧杂蒽氧基氧乙酸(5和6),1,2-二氢呋喃[2,3-c]蒽酮-2-羧酸(7)和2,3-二氢呋喃[3,2-b]蒽酮-2合成了α-羧酸(8)并测试了大鼠的利尿和尿尿排尿活性。多数x吨-3-基氧基乙酸(5)和7显示出强效的利尿活性,而8种则具有较低的利尿活性。在5c,5f,5k,5m,5o,5p,5r,7m,7p和8q中发现了泌尿外科活动。

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