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1.
Abstract: Lactate dehydrogenase and aldolase activity were reduced in lateral gastrocnemius muscle from two mouse mutants, A2G- adr and 129Re- dy , with abnormal muscle function. The activities of both of these enzymes were significantly reduced in the lateral gastrocnemius muscle from the A2G- adr mice at ages varying from 2 weeks to 32 weeks, whereas the activities in the soleus, heart, liver, and brain were the same as in the control animals. The lactate dehydrogenase isoenzymes in the lateral gastrocnemius and soleus muscles from the A2G mice were quantified, and although those of the soleus were comparable in mutant and control muscle, the lateral gastrocnemius from the adr mutant had reduced activity of LDH 5 and increased activities of the other four isoenzymes. The findings suggest that the adr mutation is expressed in the white (Type II) muscle fibres and not in the red (Type I) fibres or in any of the organs studied. It is suggested that the initiation of differentiation into Type II fibres from the embryonic form is absent or delayed in the A2G mutant. The reduced activities of lactate dehydrogenase and aldolase in 129Re- dy muscle confirm the findings of other workers.  相似文献   

2.
The lipids of gastrocnemius muscle from normal and dystrophic (dy) mice of the Bar Harbor, 129Re strain were studied. Animals were fed diets containing either 3.1% or 1.1% of total calories as linoleic acid. Lipid analyses were also done on muscle from a new mouse mutant, A2G-adr, which has abnormal muscle function, characterised by an arrested development of the righting response. These animals were fed the "high" linoleic acid diet only. Total lipid, triacylglycerol, and cholesterol were elevated in the 129Re-dy irrespective of the diet, whereas A2G-adr possessed significantly higher levels of cholesterol. Total phosphorus (micrograms P/g muscle) and cholesterol/phospholipid ratios were elevated in the dy strains only. Cardiolipin was raised in the dy ("low" linoleic diet) and adr muscle, whereas phosphatidylcholine was lower in the adr strain only. Linoleic acid esterified to phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine was elevated whereas arachidonic acid in phosphatidylserine was decreased in both mutants. Docosahexanoic acid (22:6) in all three dy phospholipids was decreased, independent of dietary treatment. The adr strain possessed normal levels of this fatty acid. The results specifically point to an abnormality in long-chain polyunsaturated fatty acid metabolism in gastrocnemius muscle in the 129Re-dy mutant; in the adr mutant they could reflect an abnormal increase in the number of muscle mitochondria.  相似文献   

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myo-Inositol is an essential biomolecule that is synthesized by myo-inositol monophosphatase (IMPase) from inositol monophosphate species. The enzymatic activity of IMPase is inhibited by lithium, a drug used for the treatment of mood swings seen in bipolar disorder. Therefore, myo-inositol is thought to have an important role in the mechanism of bipolar disorder, although the details remain elusive. We screened an ethyl nitrosourea mutant mouse library for IMPase gene (Impa) mutations and identified an Impa1 T95K missense mutation. The mutant protein possessed undetectable enzymatic activity. Homozygotes died perinatally, and E18.5 embryos exhibited striking developmental defects, including hypoplasia of the mandible and asymmetric fusion of ribs to the sternum. Perinatal lethality and morphological defects in homozygotes were rescued by dietary myo-inositol. Rescued homozygotes raised on normal drinking water after weaning exhibited a hyper-locomotive trait and prolonged circadian periods, as reported in rodents treated with lithium. Our mice should be advantageous, compared with those generated by the conventional gene knock-out strategy, because they carry minimal genomic damage, e.g. a point mutation. In conclusion, our results reveal critical roles for intracellular myo-inositol synthesis in craniofacial development and the maintenance of proper brain function. Furthermore, this mouse model for cellular inositol depletion could be beneficial for understanding the molecular mechanisms underlying the clinical effect of lithium and myo-inositol-mediated skeletal development.  相似文献   

5.
Cytochromes P450 (CYP) from the 2A subfamily are known for their roles in the metabolism of nicotine, the addictive agent in tobacco, and activation of the tobacco procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Although both the hepatic CYP2A6 and respiratory CYP2A13 enzymes metabolize these compounds, CYP2A13 does so with much higher catalytic efficiency, but the structural basis for this has been unclear. X-ray structures of nicotine complexes with CYP2A13 (2.5 Å) and CYP2A6 (2.3 Å) yield a structural rationale for the preferential binding of nicotine to CYP2A13. Additional structures of CYP2A13 with NNK reveal either a single NNK molecule in the active site with orientations corresponding to metabolites known to form DNA adducts and initiate lung cancer (2.35 Å) or with two molecules of NNK bound (2.1 Å): one in the active site and one in a more distal staging site. Finally, in contrast to prior CYP2A structures with enclosed active sites, CYP2A13 conformations were solved that adopt both open and intermediate conformations resulting from an ∼2.5 Å movement of the F to G helices. This channel occurs in the same region where the second, distal NNK molecule is bound, suggesting that the channel may be used for ligand entry and/or exit from the active site. Altogether these structures provide multiple new snapshots of CYP2A13 conformations that assist in understanding the binding and activation of an important human carcinogen, as well as critical comparisons in the binding of nicotine, one of the most widely used and highly addictive drugs in human use.  相似文献   

6.
Little is known on the cryopreservation of mouse pronuclear (PN) stage embryos. In the present experiment the mouse 2-PN stage embryos were cryopreserved by conventional freezing, straw, or open-pulled straw (OPS) vitrificaiton methods. The conventional freezing solution was 1.5 mol/L ethylene glycol (EG), and vitrification solutions were EFS30 (30% EG, Ficoll, and sucrose), EFS40 (40% EG, Ficoll, and sucrose), EDFS30 (15% EG, 15%dimethyl sulfoxide [DMSO], Ficoll, and sucrose), or EDFS40 (20% EG, 20%DMSO, Ficoll, and sucrose). The blastocyst rate of 2-PN stage embryos cryopreserved by conventional method (30.4%) was lower than those vitrified by straw method with EDFS (56.9% to 69.1%), by OPS method (66.0% to 85.7%), and that of control (80.8%) (P < 0.05). With a given vitrificaiton solution EFS30, EFS40, EDFS30, or EDFS40, the blastocyst rate of embryos vitrified by the OPS method (66.7%, 66.0%, 85.7%, or 76.9%) was higher than that of those vitrified by the straw method (46.8%, 43.8%, 69.1%, or 56.9%) (P < 0.05). When mouse 2-PN-stage embryos were vitrified with EDFS30 by straw or OPS method, the highest blastocyst rate was achieved (69.1% or 85.7%) and was similar to that of the control, respectively. The embryos transfer results revealed that the full-term development of blastocysts derived from 2-PN stage embryos vitrified by OPS method with EDFS30 (19.9%) was similar to that of the control (23.5%), and higher than that of those cryopreserved by conventional freezing (9.3%) (P < 0.05). The present research demonstrates that the OPS method, especially with EDFS30, is more effective in cryopreserving mouse 2-PN embryos.  相似文献   

7.
Abstract: Aldehyde dehydrogenase (ALDH) activity was measured in brains, livers, and hearts of 23–26-month-old and 3-month-old rats. A significant increase of ALDH activity was found in whole brain of old rats with both acetaldehyde (39%) and propionylaldehyde (15%) used as substrates. In different brain areas of old rats, with acetaldehyde used as substrate, a significant increase of ALDH activity was found in striatum (30–50%) and cerebral cortex (37%). However, no significant difference in ALDH activity was found in livers and hearts of young and old rats. Preliminary experiments showed a significant increase of aldehyde reductase activity (52%) with p -nitrobenzaldehyde used as substrate in whole brain of old rats compared with young rats. The present work indicates that an increase of ALDH activity in brain of old rats may be an adaptive phenomenon.  相似文献   

8.
Abstract: Using immunocytochemical localization, the distribution of the glycine transporters GLYT1 and GLYT2 in the developing mouse brain was studied. GLYT1 and GLYT2 immunoreactivity begins during the period of fiber outgrow and synaptogenesis. GLYT2 is first expressed in spinal and spinothalamic white matter and is followed by the expression of synaptophysin. In the postnatal stages, GLYT2 staining in the white matter disappears, and a punctuated pattern in the gray matter emerges. In contrast, in the fetal brain GLYT1 immunoreactivity coincides with gray matter neuropil and processes of radial glia. GLYT1 is distributed over a much wider area of the brain than GLYT2. However, the distribution of these two GLYTs implies that GLYT1 and GLYT2 operate in concert within the area where both are present. At the day 12 embryo stage, GLYT1 antibodies stain the liver, and later they also react with the pancreas and the gastroduodenal junction. No other organs exhibit significant GLYT1 immunoreactivity. We additionally observed the presence of GLYT1 in rat fetal cerebral cortex and hippocampus, which was not detected in fetal mouse brain. Moreover, GLYT1 immunoreactivity was found in the mouse floor plate and the ventral commissure but was not present in the same regions in rats. These findings suggest possible differences in the expression of GLYT1 between these two species.  相似文献   

9.
Pyroglutamate-modified Aβ (AβpE3-42) peptides are gaining considerable attention as potential key players in the pathology of Alzheimer disease (AD) due to their abundance in AD brain, high aggregation propensity, stability, and cellular toxicity. Overexpressing AβpE3-42 induced a severe neuron loss and neurological phenotype in TBA2 mice. In vitro and in vivo experiments have recently proven that the enzyme glutaminyl cyclase (QC) catalyzes the formation of AβpE3-42. The aim of the present work was to analyze the role of QC in an AD mouse model with abundant AβpE3-42 formation. 5XFAD mice were crossed with transgenic mice expressing human QC (hQC) under the control of the Thy1 promoter. 5XFAD/hQC bigenic mice showed significant elevation in TBS, SDS, and formic acid-soluble AβpE3-42 peptides and aggregation in plaques. In 6-month-old 5XFAD/hQC mice, a significant motor and working memory impairment developed compared with 5XFAD. The contribution of endogenous QC was studied by generating 5XFAD/QC-KO mice (mouse QC knock-out). 5XFAD/QC-KO mice showed a significant rescue of the wild-type mice behavioral phenotype, demonstrating the important contribution of endogenous mouse QC and transgenic overexpressed QC. These data clearly demonstrate that QC is crucial for modulating AβpE3-42 levels in vivo and prove on a genetic base the concept that reduction of QC activity is a promising new therapeutic approach for AD.  相似文献   

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11.
目的:观察色胺酮对结扎冠状动脉所致心肌缺血大鼠心功能、心肌病理和心肌中COX-2的影响.方法采用结扎冠状动脉左前降支致心肌缺血模型,色胺酮0.10、0.20、0.30g/kg灌胃给药21天后,观察色胺酮对心肌缺血大鼠心功能、心肌病理和心肌组织COX-2蛋白的影响.结果①色胺酮0.10g/kg对心肌缺血大鼠的心脏功能有明显的改善作用,能增强心肌收缩力,改善心肌舒张的顺应性,表现为左心室内收缩压、左心室内压最大变化速率±dp/dtmax明显升高,与模型组比较有明显差异(P<0.05);②0.10g/kg色胺酮对结扎冠状动脉所致心肌缺血大鼠能明显减轻心肌变性,心肌纤维增生和淋巴细胞浸润;③色胺酮明显抑制缺血心肌组织中COX-2蛋白,其抑制作用随剂量的增大而逐渐增强.结论0.10g/kg色胺酮对大鼠结扎冠状动脉所致心肌缺血损伤具有明显的保护作用.  相似文献   

12.
Recently, an increasing number of studies have shown that Lake Van—the biggest soda lake in the world—is polluted due to an increasing population. Studies have shown abnormalities in the Lake Van fish (Chalcalburnus tarichi), the sole fish species that inhabits the lake. Unlike the vitellogenic and mature oocytes in normal gonads, abnormal gonads show large amounts of connective tissue and young oocytes. In this study, metal levels (nickel [Ni], copper [Cu], cobalt [Co], iron [Fe], zinc [Zn], cadmium [Cd], lead [Pb], and manganese [Mn]) in the muscle, liver, gill, intestine, and gonad of Lake Van fish with normal and abnormal gonads were assessed. Further, the metal contents in the wastewater from the wastewater treatment facility situated near Lake Van in Van City were assessed. All the metal levels, except that of Zn, were high in the Lake Van environment (P?<?0.05). The highest metal content in the tissues was for Fe, while the lowest level was for Co. The Pb level was found to be very high in both fish groups. Cd was not found in the tissues of both fish groups. The levels of Fe, Cu, Pb, and Mn were not significant in the tissues of both normal and abnormal fish groups. Zn level was significantly high in the livers and gonads of fish with abnormal gonads, and Co level was significantly high only in the livers (P?<?0.05). Consequently, high levels of Zn in the liver and gonads and high levels of Co in the liver may be factors causing the abnormal gonads in the Lake Van fish.  相似文献   

13.
目的:探究轮状病毒感染性腹泻患儿血清C反应蛋白(CRP)、心肌酶谱、肝功能指标的检测意义。方法:选择2014年1月~2016年5月我院收治的110例轮状病毒感染致腹泻患儿及同期收治的85例细菌感染性腹泻患儿为研究对象,另外选择20名同期于我院体检的年龄、性别相匹配的健康幼儿为对照。比较三组人群血清C反应蛋白、白介素6、肌钙蛋白(hs-c Tn T)、肌酸激酶(CK)、同工酶(CL-MB)、门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)水平的差异及轮状病毒感染致腹泻患儿外损伤的发生情况。结果:轮状病毒感染(RV)组患儿下呼吸道感染、皮疹、心肌损伤以及肝功能损伤的发生率均显著高于细菌感染组(P0.05);RV组和细菌感染组组患儿的血清CRP、IL-6水平均显著高于健康对照组,RV组患儿的上述指标显著低于细菌感染组(P0.05);RV组患者肌钙蛋白(hs-c Tn T)、肌酸激酶(CK)、同工酶(CL-MB)、门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)水平均显著高于细菌感染组及健康对照组患儿(P0.05),细菌感染组患儿上述指标与健康对照组比较,差异无统计学意义(P0.05)。结论:血清CRP、心肌酶谱、肝功能指标联合检测对于早期轮状病毒感染性腹泻与细菌感染性腹泻的鉴别诊断有一定的参考价值。  相似文献   

14.
研究了密点麻蜥肝脏、骨骼肌、大脑组织中琥珀酸脱氢酶(SDH)、乳酸脱氢酶(LDH)活性对温度的依赖关系.结果表明:密点麻蜥3种组织中SDH在5~35℃范围内随温度的升高而升高,在35℃时达到峰值后随着温度的升高而下降,35℃可能为SDH的最适温度;3种组织的LDH活性随温度的升高而升高;大脑中的SDH和LDH活性最高.这表明SDH和LDH的活性与动物组织的能量代谢相适应.  相似文献   

15.
The mouse neuroblastoma cell line NB2A produces cellular and secreted acetylcholinesterase (AChE). After incubation of the cells for 4 days the ratio between AChE secreted into the medium and AChE in the cells was 1:1. The cell-associated enzyme could be subdivided into soluble AChE (25%) and detergent-soluble AChE (75%). Both extracts contained predominantly monomeric AChE (4.6S) and minor amounts of tetrameric AChE (10.6S), whereas the secreted AChE in the culture supernatant contained only the tetrameric form. All forms were partially purified by affinity chromatography. It could be demonstrated that the secretory and the intracellular soluble tetramers were hydrophilic, whereas the detergent-soluble tetramer was an amphiphilic protein. On the other hand the soluble and the detergent-soluble monomeric forms were amphiphilic and their activity depended on the presence of detergent. By digestion with proteinase K amphiphilic monomeric and tetrameric AChE could be converted to a hydrophilic form that no longer required detergent for catalytic activity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [3H]diisopropylfluorophosphate-labelled AChE gave one band at 64 kilodaltons (kD) under reducing conditions and two additional bands at 120 kD and 140 kD under nonreducing conditions.  相似文献   

16.
摘要 目的:探讨醒脑静联合高压氧对急性一氧化碳中毒(ACOP)患者脑功能、肝肾功能及血清氧自由基的影响。方法:选取2017年1月至2020年1月期间我院收治的ACOP患者60例,按照随机数字表法将患者分为对照组(n=30)和研究组(n=30),在常规治疗的基础上,对照组给予高压氧治疗,研究组给予醒脑静联合高压氧治疗,对比两组疗效、脑功能、肝肾功能、血清氧自由基以及平均苏醒时间、平均住院时间、迟发性脑病发生率。结果:研究组的临床总有效率为93.33%(28/30),高于对照组的70.00%(21/30)(P<0.05)。两组治疗后天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、血肌酐(Scr)、血尿素氮(BUN)均较治疗前下降,且研究组低于对照组(P<0.05)。两组治疗后丙二醛 (MDA)较治疗前下降,且研究组低于对照组(P<0.05);两组治疗后超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)均较治疗前升高,且研究组高于对照组(P<0.05)。两组治疗后年龄相关性脑白质改变(ARWMC)分级量表、美国国立卫生研究院卒中量表(NIHSS)评分均较治疗前下降,且研究组低于对照组(P<0.05);两组治疗后简易精神状态检查量表(MMSE)评分较治疗前升高,且研究组高于对照组(P<0.05)。研究组平均苏醒时间、平均住院时间均短于对照组,迟发性脑病发生率少于对照组(P<0.05)。结论:醒脑静联合高压氧治疗ACOP患者的疗效显著,有助于患者恢复,可有效清除其血清氧自由基,保护其脑功能、肝肾功能,减少迟发性脑病发生率。  相似文献   

17.
目的:探讨促红细胞生成素(EPO)对脑损伤早产儿新生儿神经行为测定(NBNA)评分、肝肾功能以及脑干听觉诱发电位的影响。方法:选取2015年2月~2018年7月期间我院收治的脑损伤早产儿117例,将上述研究对象根据随机数字表法将其分为对照组(n=58)和观察组(n=59),对照组患儿给予常规对症治疗,观察组在对照组的基础上联合EPO治疗,比较两组NBNA评分、肝肾功能以及脑干听觉诱发电位,记录两组患儿治疗期间并发症发生情况。结果:观察组纠正胎龄40周时NBNA评分高于对照组(P<0.05)。两组患儿治疗后峰间期(Ⅰ~Ⅲ波、Ⅲ~Ⅳ波、Ⅰ~Ⅳ波)、潜伏期(Ⅰ波、Ⅲ波、Ⅳ波)均较治疗前降低,且观察组低于对照组(P<0.05)。两组患儿治疗前、后尿素氮(BUN)、肌酐(Cr)、血清谷丙转氨酶(SGPT)、总胆红素(TBIL)比较差异均无统计学意义(P>0.05)。两组患儿动脉导管未闭、新生儿败血症发生率比较差异无统计学意义(P>0.05),而观察组支气管肺发育不良、颅内出血、脑干听觉诱发电位异常等发生率低于对照组(P<0.05)。结论:EPO对脑损伤早产儿具有一定的神经保护作用,能够有效保护受损神经细胞与听觉神经通路,降低脑损伤并发症的发生率,且不影响患儿的肝肾功能。  相似文献   

18.
Abstract: 5'Nucleotidase and Na+,K+-ATPase are very probably myelin-associated enzymes, although not specific for this membrane. Thus, it is important to determine their activity in dysmyelinating mutants in either CNS (quaking, jimpy, shiverer, and mld) or PNS (Trembler). CNS: The activity of 5'nucleotidase was lower in mouse than in rat (10.5 and 28.0 nmol/min/mg protein in brain, respectively). In mouse myelin, the activity was 30 nmol/min/mg protein (and 72 in rat myelin). In mutants, the brain activity was very close to normal. In contrast, ATPase, the activity of which was higher in myelin as compared with forebrain homogenate, presented a reduced activity in various 21-day-old and adult mutants, except Trembler. It was normal in 8-day-old quaking and in cerebella from mutants. PNS: ATPase was lower than in brain and reduced in most mutants, this being expected for Trembler and quaking but not for shiverer and mld. 5'-Nucleotidase activity was higher compared with that in brain homogenate (relatively stable between 10-day postnatal and adult). It was affected in the mutants; in Trembler it was nearly normal in young animals but increased during development. Thus in Trembler, two different myelin-related enzymes and a myelin-specific enzyme (CNPase) presented different developmental patterns: ATPase was always reduced, 5'-nucleotidase was normal, and CNPase was slightly below normal in young (68% of the control value); CNPase activity declined during development but 5'-nucleotidase increased (42% and 190% of the control in 60-day-old animals). It is necessary to consider these results in parallel with alterations in the PNS because of Schwann cell abnormalities. Thus, determination of these two enzymes will provide a useful tool to study myelination and myelin assembly under both normal and pathological conditions.  相似文献   

19.
目的:探讨自身免疫性肝病(AILD)患者外周血中辅助T细胞1(Th1)和辅助T细胞2(Th2)的表达情况及其与肝功能的相关性。方法:选择42例AILD患者为实验组,11例健康体检者作为对照组,采用流式细胞术检测实验组和对照组外周血单个核细胞中Th1和Th2细胞在淋巴细胞亚群中所占百分率,并检测患者肝功能,分析Th1、Th2细胞水平与肝功能血清生化指标的相关性。结果:AILD组患者Th1细胞和Th2细胞百分率均高于健康对照组(P0.05);AILD活动期患者Th1和Th2细胞百分率明显高于健康对照组,AILD缓解期患者外周血淋巴细胞亚群中Th1细胞所占比例明显降低,Th2细胞百分率较健康人群高,Th1/Th2比值明显降低。AILD患者Th1细胞百分率与血清中TBIL、DBIL、GGT水平呈正相关关系(r分别为0.428、0.472、0.511,P值分别为0.010、0.004、0.002)。Th1/Th2比值与血清中TBIL、DBIL水平呈正相关关系(r分别为0.424、0.405,P值分别为0.011、0.016)。结论:AILD患者Th1细胞和Th2细胞百分率异常升高,且Th1细胞百分率及Th1/Th2比率与AILD患者肝功能指标具有良好的相关性。  相似文献   

20.
目的:探讨糖尿病足患者肾功能和营养状态及脂质代谢与溃疡严重程度的相关性。方法:选取2015年8月-2017年12月期间我院收治的糖尿病足患者389例为研究对象,根据Wagner分级将患者分为1级组52例,2级组84例,3级组96例,4级组129例,5级组28例,对比分析五组患者肾功能指标[血肌酐(Scr)、胱抑素C(Cys C)、尿素氮(BUN)]、营养状态指标[体重指数(BMI)、血红蛋白(Hb)、血清白蛋白(Alb)]、血脂指标[甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)]水平,并分析Wagner分级与以上指标的相关性。结果:不同Wagner分级患者性别、年龄、BUN水平比较差异无统计学意义(P0.05);2级组、3级组、4级组、5级组患者的BMI、TG、HDL-C、Hb、Alb水平低于1级组,Scr、Cys C水平、吸烟史及高血压所占比例高于1级组(P0.05);4级组、5级组患者的BMI、TG、HDL-C、Hb、Alb水平低于2级组、3级组,Scr、Cys C水平、吸烟史及高血压所占比例高于2级组、3级组(P0.05)。经Spearman相关性分析显示,Wagner分级与Scr、Cys C呈正相关,与TG、HDL-C、Hb、Alb、BMI呈负相关(P0.05)。结论:糖尿病足患者Scr、Cys C与溃疡严重程度存在正相关关系,TG、HDL-C、Hb、Alb、BMI均与溃疡严重程度存在负相关关系。  相似文献   

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