BACKGROUND & AIMS: PURPOSE OF REVIEW:The conventional view in severe sepsis or septic shock is that most of the lactate that accumulates in the circulation is due to cellular hypoxia and the onset of anaerobic glycolysis. A number of papers have suggested that lactate formation during sepsis is not due to hypoxia. I discuss this hypothesis and outline the recent advances in the understanding of lactate metabolism in shock. RECENT FINDINGS:Numerous experimental data have demonstrated that stimulation of aerobic glycolysis - that is, glycolysis not attributable to oxygen deficiency - and glycogenolysis occurs not only in resting, well-oxygenated skeletal muscles but also during experimental haemorrhagic shock and experimental sepsis, and is closely linked to stimulation of sarcolemmal Na+/K+ -ATPase under epinephrine stimulation. A human study of hyperkinetic septic shock demonstrated that skeletal muscle is a leading source of lactate production by exaggerated aerobic glycolysis through Na+/K+ -ATPase stimulation. SUMMARY:There is increasing evidence that sepsis is accompanied by a hypermetabolic state, with enhanced glycolysis and hyperlactataemia. This should not be rigorously interpreted as an indication of hypoxia. It now appears, at least in the hyperkinetic state, that increased lactate production and concentration as a result of hypoxia are often the exception rather than the rule.

背景与目标： 审查的目的：严重败血症或败血性休克的传统观点是，循环中积累的大多数乳酸是由于细胞缺氧和厌氧糖酵解的开始所致。许多论文表明败血症期间乳酸的形成不是由于缺氧引起的。我讨论了这一假设，并概述了休克中乳酸代谢的最新研究进展。
最近的发现：大量的实验数据表明，有氧糖酵解的刺激-即不是由于缺氧引起的糖酵解-糖原分解不仅发生在静息的，充氧的骨骼肌中，而且还发生在实验性失血性休克和实验性败血症中，并且密切相关与肾上腺素刺激下肌膜Na / K -ATPase的刺激有关。一项针对运动过度性败血性休克的人体研究表明，骨骼肌是通过Na / K -ATPase刺激导致的过度有氧糖酵解产生乳酸的主要来源。
摘要：有越来越多的证据表明败血症伴有代谢亢进状态，并伴有糖酵解和高乳酸血症。不应将其严格解释为缺氧的征兆。现在看来，至少在运动亢进状态下，缺氧导致的乳酸产生和浓度增加通常是例外而不是规则。

BACKGROUND & AIMS: OBJECTIVE:The role of glucocorticoids production in adipose tissue in the development of metabolic disorders in humans has not been fully characterized. We investigated whether in obese subjects, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) expression in subcutaneous (SAT) and visceral (VAT) adipose tissue is associated with the occurrence of metabolic disorders and the expression of adiponectin and tumor necrosis factor alpha (TNFalpha) and two glucocorticoid-regulated adipokines able to influence the metabolic control. DESIGN AND SUBJECTS:Sixty-two obese patients were enrolled in the study. SAT and VAT samples were obtained from 13 patients undergoing bariatric surgery (body mass index (BMI) 39.1+/-5.3 kg/m(2)). SAT samples were obtained from 49 patients who underwent periumbilical biopsy (BMI 36.9+/-5.1 kg/m(2)). MEASUREMENTS:Oral glucose tolerance tests in subjects without known diabetes. Circulating glucose, lipid, insulin, adiponectin, TNFalpha and urinary-free cortisol levels. Real-time PCR to quantify mRNA levels of 11beta-HSD1, hexose-6-phosphate dehydrogenase (H6PDH), adiponectin and TNFalpha. Western blot analysis to evaluate 11beta-HSD1 protein expression. RESULTS:In the majority of the obese subjects, VAT expresses more 11beta-HSD1 than SAT. VAT 11beta-HSD1 expression was not associated with metabolic disorders. SAT 11beta-HSD1 mRNA levels were higher in subjects with than in those without metabolic syndrome (P<0.05) and in patients with type 2 diabetes compared to patients with impaired or normal glucose tolerance (P<0.0001). SAT 11beta-HSD1 expression was independently related to fasting glucose (P<0.0001) and urinary-free cortisol levels (P<0.01), and increased expression of 11beta-HSD1 was associated with increased adiponectin and TNFalpha expression and decreased serum adiponectin levels (all P's <0.05). CONCLUSIONS:In obese subjects, increased 11beta-HSD1 expression in SAT, but not in VAT, is associated with the worsening of metabolic conditions. We hypothesize that higher glucocorticoid production in adipose tissue would favor the development of metabolic disorders through a decrease in adiponectin release.

背景与目标： 目的：脂肪组织中糖皮质激素的产生在人类代谢性疾病发展中的作用尚未完全阐明。我们调查了在肥胖受试者中，皮下（SAT）和内脏（VAT）脂肪组织中的11beta-羟类固醇脱氢酶1型（11beta-HSD1）表达是否与代谢紊乱的发生以及脂联素和肿瘤坏死因子α（ TNFalpha）和两种糖皮质激素调节的脂肪因子能够影响代谢控制。
设计和受试者：62名肥胖患者参加了这项研究。 SAT和VAT样本是从13例减肥手术患者中获得的（体重指数（BMI）39.1 /-5.3 kg / m（2））。 SAT样本来自49位接受了脐周活检的患者（BMI 36.9 /-5.1 kg / m（2））。
测量：在没有已知糖尿病的受试者中进行口服葡萄糖耐量测试。循环中的葡萄糖，脂质，胰岛素，脂联素，TNFα和无尿皮质醇水平。实时PCR定量11beta-HSD1、6-磷酸己糖脱氢酶（H6PDH），脂联素和TNFalpha的mRNA水平。蛋白质印迹分析以评估11beta-HSD1蛋白表达。
结果：在大多数肥胖受试者中，VAT比SAT表达更多的11beta-HSD1。 VAT 11beta-HSD1表达与代谢异常无关。与糖耐量减低或正常的患者相比，有糖代谢的患者的SAT 11beta-HSD1 mRNA水平高于无代谢综合症的患者（P <0.05）和患有2型糖尿病的患者（P <0.0001）。 SAT 11beta-HSD1表达与空腹血糖（P <0.0001）和无尿皮质醇水平（P <0.01）独立相关，而11beta-HSD1表达增加与脂联素和TNFalpha表达增加以及血清脂联素水平降低相关（所有P ＜0.05）。
结论：在肥胖的受试者中，SAT中11beta-HSD1表达增加，而VAT中没有，与代谢状况的恶化有关。我们假设脂肪组织中较高的糖皮质激素产生将通过减少脂联素的释放而促进代谢紊乱的发展。

BACKGROUND & AIMS: :A specific chorion peroxidase is present in Aedes aegypti and this enzyme is responsible for catalyzing chorion protein cross-linking through dityrosine formation during chorion hardening. Peroxidase-mediated dityrosine cross-linking requires H(2)O(2), and this study discusses the possible involvement of the chorion peroxidase in H(2)O(2) formation by mediating NADH/O(2) oxidoreduction during chorion hardening in A. aegypti eggs. Our data show that mosquito chorion peroxidase is able to catalyze pH-dependent NADH oxidation, which is enhanced in the presence of Mn(2+). Molecular oxygen is the electron acceptor during peroxidase-catalyzed NADH oxidation, and reduction of O(2) leads to the production of H(2)O(2), demonstrated by the formation of dityrosine in a NADH/peroxidase reaction mixture following addition of tyrosine. An oxidoreductase capable of catalyzing malate/NAD(+) oxidoreduction is also present in the egg chorion of A. aegypti. The cooperative roles of chorion malate/NAD(+)oxidoreductase and chorion peroxidase on generating H(2)O(2) with NAD(+) and malate as initial substrates were demonstrated by the production of dityrosine after addition of tyrosine to a reaction mixture containing NAD(+) and malate in the presence of both malate dehydrogenase fractions and purified chorion peroxidase. Data suggest that chorion peroxidase-mediated NADH/O(2) oxidoreduction may contribute to the formation of the H(2)O(2) required for chorion protein cross-linking mediated by the same peroxidase, and that the chorion associated malate dehydrogenase may be responsible for the supply of NADH for the H(2)O(2) production.

背景与目标： 埃及伊蚊中存在特定的绒毛膜过氧化物酶，该酶负责在绒毛膜硬化过程中通过二酪氨酸形成催化绒毛膜蛋白交联。过氧化物酶介导的二氢酪氨酸交联需要H（2）O（2），本研究讨论了绒毛膜过氧化物酶在H（2）O（2）形成中的可能参与，通过在绒毛膜硬化过程中介导NADH / O（2）氧化还原在埃及埃及鸡蛋中。我们的数据表明，蚊绒毛膜过氧化物酶能够催化pH依赖性的NADH氧化，在存在Mn（2）的情况下，氧化作用会增强。分子氧是过氧化物酶催化的NADH氧化过程中的电子受体，O（2）的还原导致H（2）O（2）的产生，这是通过在NADH /过氧化物酶的反应混合物中添加二氢酪氨酸形成的二氢酪氨酸所证实的。酪氨酸。埃及曲霉的卵绒毛膜中也存在能够催化苹果酸/ NAD（）氧化还原的氧化还原酶。苹果酸/ NAD（）氧化还原酶和绒毛膜过氧化物酶在以NAD（）和苹果酸为起始底物生成H（2）O（2）时的协同作用通过向含有NAD的反应混合物中添加酪氨酸后生成二酪氨酸来证明（）和苹果酸，同时存在苹果酸脱氢酶馏分和纯化的绒毛膜过氧化物酶。数据表明绒毛膜过氧化物酶介导的NADH / O（2）氧化还原可能有助于由相同的过氧化物酶介导的绒毛膜蛋白交联所需的H（2）O（2）的形成，并且绒毛膜相关的苹果酸脱氢酶可能负责为H（2）O（2）生产提供NADH。

BACKGROUND & AIMS: :Catch crop candidates (corn, guinea grass) for recovering nutrients from farm soil and aquatic plants (water caltrop, water hyacinth) were utilized to produce L-lactic acid. The efficiencies ofpre-treatment methods for enzymatic saccharification and L-lactate production of two fermentation processes, thermophilic simultaneous saccharification and fermentation (SSF), as well as separate saccharification and fermentation, were compared. Conditions were set at 55 degrees C and pH 5.5 for non-sterile fermentation. Alkaline/peroxide pre-treatment proved the most effective for saccharification in pre-treated corn, guinea grass, water caltrop and water hyacinth with glucose yields of 0.23, 0.20, 0.11 and 0.14 g/g-dry native biomass (24-hour incubation period), respectively. Examination of the two types of thermophilic L-lactate fermentation employed following alkaline/peroxide pre-treatment and saccharification demonstrated that the L-lactate yield obtained using SSF (0.15 g/g in the case of corn) was lower than that obtained using separate saccharification and fermentation (0.28 g/g in the case of corn). The lower yield obtained from SSF is likely to have resulted from the saccharification conditions used in the present study, as the possibility of cellulase deactivation during SSF by thermophilic L-lactate producing bacteria existed. A cellulase that retains high activity levels under non-sterile conditions and a L-lactate producer without cellulose hydrolysis activity would be required in order for SSF to serve as an effective method of L-lactate production.

背景与目标： ：利用候选农作物（玉米，几内亚草）从农场土壤和水生植物（菱角，水葫芦）中回收营养，以生产L-乳酸。比较了酶促糖化和L-乳酸生产两个发酵过程（高温同步糖化和发酵（SSF），以及单独的糖化和发酵）的预处理方法的效率。非无菌发酵的条件设定在55摄氏度和pH 5.5。碱性/过氧化物预处理被证明对预处理的玉米，豚鼠草，菱角和水葫芦最有效的糖化作用，其葡萄糖产量分别为干自然生物量0.23、0.20、0.11和0.14 g / g（24小时培养期） ）， 分别。对碱/过氧化物预处理和糖化后使用的两种嗜热L-乳酸发酵进行的检查表明，使用SSF获得的L-乳酸产量（对于玉米为0.15 g / g）低于使用单独糖化获得的L-乳酸产量和发酵（对于玉米为0.28 g / g）。由于存在嗜热L-乳酸的细菌在SSF中纤维素酶失活的可能性，本研究中使用的糖化条件可能导致SSF的收率降低。为了使SSF成为生产L-乳酸的有效方法，将需要在非无菌条件下保持高活性水平的纤维素酶和没有纤维素水解活性的L-乳酸生产者。

BACKGROUND & AIMS: During a screen for respiration competent yeast mutants that were unable to grow with acetate as a carbon source, two idh2 cit1 double mutants were identified. These strains were defective in the catalytic subunit of the NAD(+)-dependent isocitrate dehydrogenase and citrate synthase of the tricarboxylic acid (TCA) cycle. The strains harboring the idh2 alleles from these strains had two unusual phenotypes. First, their growth on many nonfermentable carbon sources was much poorer than strains containing other idh2 mutations. Second, the poor growth phenotype could be suppressed by the presence of mutations in CIT1 and other genes encoding oxidative functions. Spontaneous suppressor mutants that restore fast growth on glycerol medium to strains harboring two idh2 alleles were isolated, and a large percentage of the suppressor mutations have been identified within the CIT1 gene and at several other loci. Elevated levels of several TCA cycle proteins were observed in these idh2 mutants that were not observed in the presence of suppressing cit1 mutations. Citrate and isocitrate concentrations were also elevated in the idh2 mutants, but probably not to toxic levels. Five idh2 alleles were sequenced to understand the defects of the two classes of mutations. Sequence analysis indicated that the poor growth phenotype was caused by the loss of Idh2p protein. Similarly, eight cit1 alleles were sequenced to understand their characteristics as glycerol suppressors of idh2. These and other studies indicate that any mutation within CIT1 was capable of suppressing the idh2 mutations. Several models to explain these interactions are discussed.

背景与目标： 在对呼吸的筛选中，不能用乙酸盐作为碳源生长的能干酵母突变体，鉴定出两个idh2 cit1双突变体。这些菌株在三羧酸（TCA）循环的NAD（）依赖性异柠檬酸脱氢酶和柠檬酸合酶的催化亚基中存在缺陷。包含来自这些菌株的idh2等位基因的菌株具有两种不同的表型。首先，它们在许多不可发酵碳源上的生长要比含有其他idh2突变的菌株差得多。第二，生长不良的表型可以被CIT1和其他编码氧化功能的基因突变的存在所抑制。分离出自发性抑制突变体，该突变体可在甘油培养基上恢复到含有两个idh2等位基因的菌株的快速生长，并且已在CIT1基因和其他几个基因座中鉴定出很大比例的抑制突变。在这些idh2突变体中观察到几种TCA循环蛋白的水平升高，而在抑制cit1突变的情况下未观察到。在idh2突变体中柠檬酸和异柠檬酸浓度也升高，但可能没有达到毒性水平。对五个idh2等位基因进行了测序，以了解这两类突变的缺陷。序列分析表明，不良的生长表型是由Idh2p蛋白的丢失引起的。同样，对八个cit1等位基因进行了测序，以了解其作为idh2甘油抑制剂的特征。这些研究和其他研究表明，CIT1中的任何突变都能够抑制idh2突变。讨论了解释这些相互作用的几种模型。

BACKGROUND & AIMS: :This study compared the oxygen uptake (VO2) and running velocity at which the lactate threshold (LT), the ventilatory threshold (VT), and the maximal lactate steady state (MSSLA), and the maximal VO2 steady state (MSSVO2) occurred in 11 trained male runners (mean age = 22.4 years, range 18-28 years). Each underwent an incremental treadmill test to exhaustion. The LT was defined by a systematic, continuous increase in arterialised venous blood lactate; the VT was determined by an abrupt rise in VE.VO2(-1) without an increase in VE.VCO2(-1). Each subject also completed a series of steady state treadmill runs of 20 minutes duration. The MSSLA was determined as the highest velocity and VO2 at which lactate concentration increased by less than 0.2 mmol.l-1 from minute 10 to minute 20. The MSSVO2 was determined as the highest velocity or VO2 at which a steady state in VO2 was not delayed for more than 3 minutes (with a steady state defined as VO2 within 0.2 l.min-1 of the average VO2 over the last 10 minutes of each test). Each subject also completed a 5 km time trial run to assess performance. No significant differences were found among the four variables expressed either as VO2 or velocity. Significant correlations were found between MSSLA and MSSVO2 (r = 0.74) expressed as VO2, and between MSSLA and MSSVO2 (r = 0.90), MSSVO2 and VT (r = 0.70) and MSSLA and VT (r = 0.67) expressed as velocity. A stepwise regression analysis found MSSLA (expressed as velocity) to be the best predictor of 5 km performance (r = 0.87). It was concluded that (a) MSSLA and MSSVO2 are closely related, and (b) MSSLA is a good predictor of performance and may be an important, objective measure of cardiorespiratory endurance capacity.

背景与目标： ：本研究比较了在以下情况下发生的乳酸阈值（LT），通气阈值（VT），最大乳酸稳态（MSSLA）和最大VO2稳态（MSSVO2）的摄氧量（VO2）和运行速度。 11位训练有素的男性跑步者（平均年龄= 22.4岁，范围18-28岁）。每个人都进行了递增的跑步机测试，以消耗体力。 LT的定义是动脉血静脉血乳酸的系统性，持续增加。 VT是由VE.VO2（-1）的突然升高而不是VE.VCO2（-1）的升高确定的。每个受试者还完成了一系列持续20分钟的稳态跑步机。 MSSLA被确定为从10分钟到20分钟乳酸浓度增加小于0.2 mmol.l-1的最高速度和VO2。MSSVO2被确定为VO2中未达到稳态的最高速度或VO2。延迟超过3分钟（在每次测试的最后10分钟内，稳定状态定义为VO2在平均VO2的0.2 l.min-1之内）。每个受试者还完成了5公里的时间试跑以评估表现。在以VO2或速度表示的四个变量之间没有发现显着差异。发现MSSLA和MSSVO2之间（r = 0.74）表示为VO2，MSSLA和MSSVO2（r = 0.90），MSSVO2和VT（r = 0.70）和MSSLA和VT（r = 0.67）表示为显着相关。逐步回归分析发现，MSSLA（表示为速度）是5 km表现的最佳预测指标（r = 0.87）。结论是：（a）MSSLA和MSSVO2密切相关，并且（b）MSSLA是性能的良好预测指标，并且可能是心肺耐力的重要客观指标。

BACKGROUND & AIMS: :Mammalian Peptidoglycan Recognition Proteins (PGRPs) kill bacteria through induction of synergistic oxidative, thiol, and metal stress. PGRPs induce oxidative stress in bacteria through a block in the respiratory chain, which results in decreased respiration and incomplete reduction of oxygen (O2) to hydrogen peroxide (H2O2). In this study we identify the site of PGRP-induced generation of H2O2 in Escherichia coli. Tn-seq screening of E. coli Tn10 insertion library revealed that mutants in formate dehydrogenase (FDH) genes had the highest survival following PGRP treatment. Mutants lacking functional FDH-O had abolished PGRP-induced H2O2 production and the highest resistance to PGRP-induced killing, and formate enhanced PGRP-induced killing and H2O2 production in an FDH-dependent manner. Mutants in ubiquinone synthesis (but not menaquinone and demethylmenaquinone) and cytochrome bd-I (but not cytochromes bo3 and bd-II) also had completely abolished PGRP-induced H2O2 production and high resistance to PGRP-induced killing. Because electrons in the respiratory chain flow from dehydrogenases' substrates through quinones and then cytochromes to O2, these results imply that the site of PGRP-induced incomplete reduction of O2 to H2O2 is downstream from dehydrogenases and ubiquinone at the level of cytochrome bd-I, which results in oxidative stress. These results reveal several essential steps in PGRP-induced bacterial killing.

背景与目标： ：哺乳动物肽聚糖识别蛋白（PGRP）通过诱导协同氧化，硫醇和金属胁迫杀死细菌。 PGRP通过呼吸链中的阻滞诱导细菌中的氧化应激，导致呼吸减少，氧气（O2）还原为过氧化氢（H2O2）的过程不完全。在这项研究中，我们确定了PGRP诱导大肠杆菌中H2O2生成的位点。大肠杆菌Tn10插入文库的Tn-seq筛选显示，在进行PGRP处理后，甲酸脱氢酶（FDH）基因中的突变体具有最高的存活率。缺乏功能性FDH-0的突变体废除了PGRP诱导的H2O2产生和对PGRP诱导的杀灭的最高抗性，甲酸盐以FDH依赖性方式增强了PGRP诱导的杀灭和H2O2的产生。泛醌合成中的突变体（但不是甲萘醌和去甲基甲萘醌）和细胞色素bd-I（但不是细胞色素bo3和bd-II）的突变体也完全消除了PGRP诱导的H2O2产生，并且对PGRP诱导的杀灭具有很高的抵抗力。由于呼吸链中的电子从脱氢酶的底物流经醌，然后从细胞色素流向O2，因此这些结果表明，PGRP诱导的O2不完全还原为H2O2的位点在脱氢酶和泛醌的下游位于细胞色素bd-I的水平，导致氧化应激。这些结果揭示了PGRP诱导的细菌杀伤中的几个基本步骤。

BACKGROUND & AIMS: BACKGROUND:Plasmodium lactate dehydrogenase (pLDH) is a major target in diagnosing the erythrocytic stage of malaria parasites because it is highly expressed during blood-stage parasites and is distinguished from human LDH. Rapid diagnostic tests (RDTs) for malaria use pLDH as a target antigen; however, genetic variations in pLDH within the natural population threaten the efficacy of pLDH-based RDTs. METHODS:Genetic polymorphisms of Plasmodium vivax LDH (PvLDH) and Plasmodium falciparum LDH (PfLDH) in Myanmar isolates were analysed by nucleotide sequencing analysis. Genetic polymorphisms and the natural selection of PvLDH and PfLDH were analysed using DNASTAR, MEGA6, and DnaSP ver. 5.10.00 programs. The genetic diversity and natural selection of global PvLDH and PfLDH were also analysed. The haplotype network of global PvLDH and PfLDH was constructed using NETWORK ver. 5.0.0.3. Three-dimensional structures of PvLDH and PfLDH were built with YASARA Structure ver. 18.4.24 and the impact of mutations on structural change and stability was evaluated with SDM ver. 2, CUPSAT and MAESTROweb. RESULTS:Forty-nine PvLDH and 52 PfLDH sequences were obtained from Myanmar P. vivax and P. falciparum isolates. Non-synonymous nucleotide substitutions resulting in amino acid changes were identified in both Myanmar PvLDH and PfLDH. Amino acid changes were also identified in the global PvLDH and PfLDH populations, but they did not produce structural alterations in either protein. Low genetic diversity was observed in global PvLDH and PfLDH, which may be maintained by a strong purifying selection. CONCLUSION:This study extends knowledge for genetic diversity and natural selection of global PvLDH and PfLDH. Although amino acid changes were observed in global PvLDH and PfLDH, they did not alter the conformational structures of the proteins. These suggest that PvLDH and PfLDH are genetically well-conserved in global populations, which indicates that they are suitable antigens for diagnostic purpose and attractive targets for drug development.

背景与目标： 背景：乳酸疟原虫脱氢酶（pLDH）是诊断疟疾寄生虫的红细胞阶段的主要目标，因为它在血液阶段的寄生虫中高度表达，并且与人LDH有所区别。疟疾快速诊断检测（RDT）使用pLDH作为靶抗原。然而，自然种群中pLDH的遗传变异威胁了基于pLDH的RDT的功效。
方法：采用核苷酸测序技术分析缅甸分离株间日疟原虫LDH（PvLDH）和恶性疟原虫LDH（PfLDH）的基因多态性。使用DNASTAR，MEGA6和DnaSP版本分析了PvLDH和PfLDH的遗传多态性和自然选择。 5.10.00程序。还分析了全球PvLDH和PfLDH的遗传多样性和自然选择。使用NETWORK ver构建了全局PvLDH和PfLDH的单倍型网络。 5.0.0.3。使用YASARA Structure ver。构建了PvLDH和PfLDH的三维结构。 18.4.24，并使用SDM ver。评估了突变对结构变化和稳定性的影响。 2，CUPSAT和MAESTROweb。
结果：从缅甸间日疟和恶性疟原虫分离物中获得了49个PvLDH和52个PfLDH序列。在缅甸PvLDH和PfLDH中均鉴定出导致氨基酸变化的非同义核苷酸取代。在全球PvLDH和PfLDH人群中也发现了氨基酸变化，但它们在两种蛋白质中均未产生结构改变。在全球PvLDH和PfLDH中观察到低的遗传多样性，这可以通过强力的纯化选择来维持。
结论：本研究扩展了全球PvLDH和PfLDH的遗传多样性和自然选择知识。尽管在整体PvLDH和PfLDH中观察到了氨基酸变化，但它们并没有改变蛋白质的构象结构。这些表明PvLDH和PfLDH在全球人群中在遗传上是保守的，这表明它们是适合用于诊断目的的抗原和有吸引力的药物开发靶标。

BACKGROUND & AIMS: :A differentiation, based on morphological characters, between Stylonychia mytilus and Stylonychia lemnae is very difficult, especially for non-specialists. These two sibling species were considered as one species, S. mytilus, until detailed cytological and genetic studies could show the existence of two genetically isolated varieties. Further morphological and biochemical analyses verified the separation and finally in 1983 a new species S. lemnae was described. The examination of several isoenzymes revealed unambiguous differences in the banding pattern of isocitrate dehydrogenase (IDH) between these two species. Therefore, the IDH gene of 30 isolates of S. lemnae and S. mytilus coming from various regions all over the world were amplified and sequenced. The sequence analyses revealed intraspecific as well as interspecific substitutions, which were used for the development of species-specific PCR primers for both species. Application of these species-specific primer pairs now allows a very easy and clear identification of both sibling species.

背景与目标： ：在形态特征上，Mytilus和Stylonychia lemnae之间的区分是非常困难的，特别是对于非专业人士而言。直到详细的细胞学和遗传学研究表明存在两个遗传分离的变种之前，这两个兄弟姐妹种才被认为是一种S. mytilus。进一步的形态学和生化分析证实了分离，最后在1983年描述了一个新种S. lemnae。对几种同工酶的检查表明，这两个物种之间的异柠檬酸脱氢酶（IDH）的带谱模式无明显差异。因此，扩增并测序了来自世界各地的30株柠檬肉链球菌和枯草链球菌的IDH基因。序列分析揭示了种内和种间取代，这些被用于开发两个物种的物种特异性PCR引物。现在，这些物种特异性引物对的应用可以非常轻松，清晰地鉴定两个同胞物种。

BACKGROUND & AIMS: OBJECTIVE:To elucidate the function of cytosolic malate dehydrogenase (Mor2) in oocyte maturation and embryo development using RNA interference (RNAi). DESIGN:Experimental animal study. SETTING:Research unit of university. ANIMAL(S):Female 4-week-old (C57/BL6) mice. INTERVENTION(S):Isolation of immature germinal vesicle (GV) oocytes or fertilized pronucleus (PN) embryos, microinjection of Mor2 double-stranded RNA (dsRNA), and reverse transcription and polymerase chain reaction (RT-PCR) analysis to investigate Mor2-specific messenger RNA (mRNA) knockdown. MAIN OUTCOME MEASURE(S):Relative changes in mRNA levels after microinjection of Mor2 dsRNA and in rates of oocyte maturation and preimplantation embryo development. RESULT(S):Mor2 mRNA mostly was knocked down in germinal vesicle- and metaphase I (MI)-arrested oocytes, compared with metaphase II (MII)-developed oocytes, after microinjection of Mor2 dsRNA and in vitro culture for 16 hours. In vitro oocyte maturation was significantly decreased (34%), compared with noninjected (73.4%) and buffer-injected (67.5%) control groups. The rate of blastocyst development (48.1%) was lower in the Mor2 dsRNA-injected group than in buffer-injected control (88.2%). CONCLUSION(S):In the present study, the function of Mor2 was analyzed with the aid of RNAi. On the basis of the data obtained, we propose that Mor2 is an essential factor for oocyte maturation and embryo development in mouse.

背景与目标： 目的：利用RNA干扰技术（RNAi）阐明胞质苹果酸脱氢酶（Mor2）在卵母细胞成熟和胚胎发育中的功能。
设计：实验动物研究。
单位：大学研究单位。
动物：4周龄雌性（C57 / BL6）小鼠。
干预：分离未成熟的生小泡（GV）卵母细胞或受精的原核（PN）胚胎，显微注射Mor2双链RNA（dsRNA），以及反转录和聚合酶链反应（RT-PCR）分析以研究Mor2-特定的信使RNA（mRNA）敲低。
主要观察指标：微量注射Mor2 dsRNA后mRNA水平以及卵母细胞成熟和植入前胚胎发育的相对变化。
结果：显微注射Mor2 dsRNA并进行体外培养16小时后，与生中期II（MII）发育的卵母细胞相比，生胚囊泡和中期I（MI）发育的卵母细胞中Mor2 mRNA大部分被敲低。与未注射（73.4％）和注射缓冲液（67.5％）的对照组相比，体外卵母细胞成熟显着降低（34％）。注入Mor2 dsRNA的组的胚泡发育率（48.1％）低于注入缓冲液的对照组（88.2％）。
结论：在本研究中，借助于RNAi分析了Mor2的功能。根据获得的数据，我们建议Mor2是小鼠卵母细胞成熟和胚胎发育的重要因素。

BACKGROUND & AIMS: :Antibodies raised against NdhH and NdhB detected these proteins in the thylakoid membrane of Synechocystis sp. strain PCC 6803, but not in a purified cytoplasmic membrane. We conclude that NAD(P)H dehydrogenase is largely, if not exclusively, confined to the thylakoid membrane.

背景与目标： ：针对NdhH和NdhB产生的抗体在Synechocystis sp。的类囊体膜中检测到了这些蛋白。株PCC 6803，但不在纯化的细胞质膜中。我们得出的结论是，NAD（P）H脱氢酶在很大程度上（如果不是唯一的话）局限于类囊体膜。

BACKGROUND & AIMS: OBJECTIVE:Ringer's lactate may improve early systemic inflammation during critical illnesses like severe acute pancreatitis, which are associated with hypocalcemia. Ringer's lactate is buffered and contains lactate and calcium. We, thus analyzed extracellular calcium or lactate's effects on the mechanisms, intermediary markers, and organ failure in models mimicking human disease with nonesterified fatty acid (NEFA) elevation. METHODS:Meta-analyses and experimental studies were performed. Experimentally, extracellular calcium and lactate were compared in their interaction with linoleic acid (LA; a NEFA increased in human severe pancreatitis), and its subsequent effects on mitochondrial depolarization and cytosolic calcium signaling resulting in cell injury. In vivo, the effect of LA was studied on organ failure, along with the effect of calcium or lactate (pH 7.4) on severe acute pancreatitis-associated organ failure. A meta-analysis of human randomized control trials comparing Ringer's lactate to normal saline was done, focusing on necrosis and organ failure. RESULTS:Calcium reacted ionically with LA and reduced lipotoxic necrosis. In vivo, LA induced organ failure and hypocalcemia. During severe pancreatitis, calcium supplementation in saline pH 7.4, unlike lactate, prevented hypocalcemia, increased NEFA saponification, reduced circulating NEFA and C-reactive protein , reduced pancreatic necrosis adjacent to fat necrosis, and normalized shock (carotid pulse distension) and blood urea nitrogen elevation on day 1. This, however, did not prevent the later increase in serum NEFA which caused delayed organ failure. Meta-analysis showed Ringer's lactate reduced necrosis, but not organ failure, compared with normal saline. CONCLUSION:Hypocalcemia occurs due to excess NEFA binding calcium during a critical illness. Ringer's lactate's early benefits in systemic inflammation are by the calcium it provides reacting ionically with NEFA. This, however, does not prevent later organ failure from sustained NEFA generation. Future studies comparing calcium supplemented saline resuscitation to Ringer's lactate may provide insights to this pathophysiology.

背景与目标： 目的：在严重的急性胰腺炎等严重疾病（与低钙血症有关）期间，林格氏乳酸盐可能会改善早期的全身炎症。林格氏乳酸被缓冲并且包含乳酸和钙。因此，我们在模拟非酯化脂肪酸（NEFA）升高的人类疾病的模型中，分析了细胞外钙或乳酸对机制，中介标志物和器官衰竭的影响。
方法：进行了荟萃分析和实验研究。实验上，比较了细胞外钙和乳酸与亚油酸（LA；人严重胰腺炎中NEFA升高）的相互作用，以及其对线粒体去极化和胞质钙信号传导导致细胞损伤的后续作用。在体内，研究了LA对器官衰竭的作用，以及钙或乳酸（pH 7.4）对严重急性胰腺炎相关器官衰竭的作用。对人的随机对照试验进行了荟萃分析，比较了林格氏乳酸和生理盐水，重点是坏死和器官衰竭。
结果：钙离子与LA发生离子反应，减少了脂毒性坏死。在体内，LA诱发器官衰竭和低钙血症。在严重的胰腺炎期间，与乳酸不同，在pH 7.4的盐水中补充钙可预防低血钙症，增加NEFA皂化，减少循环NEFA和C反应蛋白，减少与脂肪坏死相邻的胰腺坏死，并使休克恢复正常（颈动脉脉搏扩张）和血尿素氮在第1天升高。但是，这并不能阻止后来的血清NEFA升高而导致器官功能衰竭延迟。荟萃分析显示，与生理盐水相比，林格氏乳酸可减少坏死，但不会减少器官衰竭。
结论：低钙血症的发生是由于危重病期间过多的NEFA结合钙引起的。林格氏乳酸盐在全身性炎症中的早期益处是钙提供的钙与NEFA发生离子反应。但是，这不能防止持续的NEFA产生导致随后的器官衰竭。未来将钙补充盐水复苏与林格氏乳酸进行比较的研究可能会为这种病理生理学提供见解。

BACKGROUND & AIMS: :Studies of initial activities of carbon monoxide dehydrogenase (CODH) from Rhodospirillum rubrum show that CODH is mostly inactive at redox potentials higher than -300 mV. Initial activities measured at a wide range of redox potentials (0--500 mV) fit a function corresponding to the Nernst equation with a midpoint potential of -316 mV. Previously, extensive EPR studies of CODH have suggested that CODH has three distinct redox states: (i) a spin-coupled state at -60 to -300 mV that gives rise to an EPR signal termed C(red1); (ii) uncoupled states at <-320 mV in the absence of CO(2) referred to as C(unc); and (iii) another spin-coupled state at <-320 mV in the presence of CO(2) that gives rise to an EPR signal termed C(red2B). Because there is no initial CODH activity at potentials that give rise to C(red1), the state (C(red1)) is not involved in the catalytic mechanism of this enzyme. At potentials more positive than -380 mV, CODH recovers its full activity over time when incubated with CO. This reductant-dependent conversion of CODH from an inactive to an active form is referred to hereafter as "autocatalysis." Analyses of the autocatalytic activation process of CODH suggest that the autocatalysis is initiated by a small fraction of activated CODH; the small fraction of active CODH catalyzes CO oxidation and consequently lowers the redox potential of the assay system. This process is accelerated with time because of accumulation of the active enzyme.

背景与目标： ：来自红红螺旋藻的一氧化碳脱氢酶（CODH）初始活性的研究表明，在氧化还原电势高于-300 mV时，CODH大部分是无活性的。在宽范围的氧化还原电势（0--500 mV）下测得的初始活动拟合了一个与Nernst方程相对应的函数，中点电势为-316 mV。以前，对CODH进行的广泛EPR研究表明，CODH具有三种不同的氧化还原状态：（i）-60至-300 mV的自旋耦合状态，产生称为C（red1）的EPR信号； （ii）在不存在CO（2）的情况下<-320 mV的未耦合状态，称为C（unc）； （iii）在存在CO（2）的情况下<-320 mV的另一种自旋耦合状态，会产生称为C（red2B）的EPR信号。因为在产生C（red1）的电位上没有初始CODH活性，所以状态（C（red1））不参与该酶的催化机理。在比-380 mV更高的电势下，当与CO一起孵育时，CODH随时间恢复其全部活性。此后，依赖于还原剂的CODH从无活性形式转化为活性形式的过程称为“自催化”。对CODH的自催化活化过程的分析表明，自催化是由一小部分活化的CODH引发的。少量的活性CODH催化CO氧化，因此降低了测定系统的氧化还原电位。由于活性酶的积累，该过程随时间加速。

BACKGROUND & AIMS: PURPOSE:Thiamine functions as an important cofactor in aerobic metabolism and thiamine deficiency can contribute to lactic acidosis. Although increased rates of thiamine deficiency have been described in diabetic outpatients, this phenomenon has not been studied in relation to diabetic ketoacidosis (DKA). In the present study, we hypothesize that thiamine deficiency is associated with elevated lactate in patients with DKA. MATERIALS AND METHODS:This was a prospective observational study of patients presenting to a tertiary care center with DKA. Patient demographics, laboratory results, and outcomes were recorded. A one-time blood draw was performed and analyzed for plasma thiamine levels. RESULTS:Thirty-two patients were enrolled. Eight patients (25%) were thiamine deficient, with levels lower than 9 nmol/L. A negative correlation between lactic acid and plasma thiamine levels was found (r = -0.56, P = .002). This relationship remained significant after adjustment for APACHE II scores (P = .009). Thiamine levels were directly related to admission serum bicarbonate (r = 0.44, P = .019), and patients with thiamine deficiency maintained lower bicarbonate levels over the first 24 hours (slopes parallel with a difference of 4.083, P = .002). CONCLUSIONS:Patients with DKA had a high prevalence of thiamine deficiency. Thiamine levels were inversely related to lactate levels among patients with DKA. A study of thiamine supplementation in DKA is warranted.

背景与目标： 目的：硫胺素是有氧代谢中的重要辅助因子，硫胺素缺乏可导致乳酸性酸中毒。尽管已在糖尿病门诊患者中描述了硫胺素缺乏症的发病率上升，但尚未针对糖尿病酮症酸中毒（DKA）对该现象进行研究。在本研究中，我们假设硫胺素缺乏与DKA患者的乳酸升高有关。
材料与方法：这是一项针对前瞻性观察性研究，研究对象是就诊患有DKA的三级护理中心的患者。记录患者的人口统计学，实验室结果和结果。进行一次抽血并分析血浆硫胺素水平。
结果：32例患者入选。 8名患者（25％）缺乏硫胺素，水平低于9 nmol / L。发现乳酸与血浆硫胺素水平呈负相关（r = -0.56，P = 0.002）。在调整了APACHE II分数之后，这种关系仍然很明显（P = .009）。硫胺素水平与入院血清碳酸氢盐水平直接相关（r = 0.44，P = .019），硫胺素缺乏症患者在最初的24小时内维持较低的碳酸氢盐水平（斜率平行于4.083，P = .002）。
结论：DKA患者的硫胺素缺乏症患病率很高。在DKA患者中，硫胺素水平与乳酸水平成反比。必须对DKA中的硫胺素补充剂进行研究。

BACKGROUND & AIMS: :Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathic disease in Taiwan. The mass neonatal screening of G6PD deficiency by fluorometric spot test in Taiwan was started with a pilot program in 1984. The nationwide screening was started on July 1, 1987, and a follow-up system comprising of eighteen referral hospitals, including outlying islands, was organized for confirmatory test, medical care and genetic counseling. From July 1987 to December 1997, 2,971,192 heel blood samples collected on filter paper from 1,143 delivery units were screened by four neonatal screening centers. 46,570 cases were confirmed as G6PD deficiency is estimated to be around 2.1% (male 3.1%, female 0.9%) in Taiwan. The coverage rate of neonatal screening was 99% in 1997. To assess the reliability of the confirmatory test, an external quality assurance (QA) program for G6PD assay was developed. Periodically, 3 or 5 lyophilized quality control materials with different activities of G6PD were sent to each referral hospital by speed post delivery in dry ice. From January 1988 to June 1998, 85 QA services were performed. Two hundred and seven (13.5%) abnormal QA results were found, which were attributed to clerk (11.6%), procedural (16.4%), and instrumental errors (47.3%). In aid to confirm G6PD deficiency, a method to detect the G6PD mutation by using the dried blood samples was developed. The frequencies of the mutant alleles in Taiwan were determined to be 46.8% (1376G > T), 16.2% (1388G > A), 7.9% (95A > G), 6.5% (493A > G), 5.6% (392G >T), 4.6% (1024C > T), 0.5% (487G > A) and 0.5% (519C > G), respectively.

背景与目标： ：6-磷酸葡萄糖脱氢酶（G6PD）缺乏症是台湾最常见的酶促疾病。台湾在1984年通过试点计划开始了通过荧光斑点试验对G6PD缺乏症进行大规模新生儿筛查。1987年7月1日开始在全国范围内进行筛查，并建立了包括18个转诊医院（包括离岛）的随访系统。组织进行验证性测试，医疗和遗传咨询。从1987年7月至1997年12月，由四个新生儿筛查中心筛查了从1,143个分娩单位收集在滤纸上的2,971,192足跟血样品。在台湾，已确认有46,570例病例，因为G6PD缺乏症估计约为2.1％（男性3.1％，女性0.9％）。 1997年，新生儿筛查的覆盖率为99％。为评估验证性测试的可靠性，开发了用于G6PD分析的外部质量保证（QA）程序。通过在干冰中快速分娩，定期将3或5种具有不同G6PD活性的冻干质量控制材料发送到每个转诊医院。从1988年1月到1998年6月，共进行了85次质量检查服务。发现了207个（13.5％）异常QA结果，这归因于业务员（11.6％），程序（16.4％）和工具错误（47.3％）。为了帮助确认G6PD缺乏症，开发了一种使用干血样品检测G6PD突变的方法。台湾的突变等位基因频率确定为46.8％（1376G> T），16.2％（1388G> A），7.9％（95A> G），6.5％（493A> G），5.6％（392G> T） ），4.6％（1024C> T），0.5％（487G> A）和0.5％（519C> G）。