神经节苷脂联合α-硫辛酸治疗糖尿病神经源性膀胱临床观察

目的：观察α-硫辛酸、神经节苷脂联合治疗糖尿病神经源性膀胱的临床疗效。方法：60例2型糖尿病神经源性膀胱患者,随机分为α-硫辛酸治疗对照组、神经节苷脂治疗对照组,联合治疗组,疗程30d,观察症状体征及治疗前后B超膀胱残余尿量症状的变化,比较不同方案的疗效。结果：α-硫辛酸治疗对照组有效率90％,神经节苷脂治疗对照组有效率90％,联合治疗组有效率95％两组间无统计学差异（P〉0．05）,但3组的治愈率分别为90．0％、50．0％、60．0%,治疗组的治愈率高于两个对照组,有统计学差异（P〈0．05）。结论：α-硫辛酸和神经节苷脂联合治疗糖尿病神经源性膀胱有较好的临床疗效,值得临床推广。     

α-硫辛酸联合空气波压力治疗老年糖尿病周围神经病变疗效观察

目的:探讨α-硫辛酸联合空气波压力治疗仪治疗老年糖尿病周围神经病变的临床疗效.方法:将2010年1月至2012年6月我院收治的60例老年糖尿病周围神经病变患者随机分成对照组和治疗组两组,每组各30例.对照组患者单独用α-硫辛酸300 mg加入生理盐水250 mL中静滴,每日1次;而治疗组采用相同剂量的α-硫辛酸治疗,并联合空气波压力治疗仪,每次45分钟,1次/日.观察和比较治疗前及治疗2周后两组患者自觉症状、运动神经传导速度及感觉神经传导速度的差异.结果:对照组和治疗组的治疗总有效率分别为63.3％和86.7％,治疗组显著高于对照组,两组差异有统计学意义(P＜0.05);治疗后,两组患者的运动和感觉神经传导速度均较治疗前提高,且治疗组的神经传导速度较对照组提高更明显,差异有统计学意义(P＜0.05).结论:α-硫辛酸联合空气波压力治疗老年糖尿病周围神经病变的疗效较单用α-硫辛酸更好,且简便安全,值得临床推广.     

α-硫辛酸联合前列地尔对糖尿病周围神经病变患者血清炎症因子及神经传导速度的影响

目的:探讨α-硫辛酸联合前列地尔对糖尿病周围神经病变患者的疗效及对血清炎症因子、神经传导速度的影响。方法:选取我院2015年6月-2017年6月治疗的130例糖尿病周围神经病变患者,随机分为观察组(n=65)和对照组(n=65)。其中对照组患者采用前列地尔治疗,观察组患者在此基础上联合α-硫辛酸治疗,两组患者均连续治疗2周。对两组患者的临床疗效、治疗前后的神经传导速度、血清炎症因子水平、多伦多临床神经病变评分系统(TCSS)、视觉模拟评分(VAS)、不良反应发生率等指标进行综合评价对比。结果:观察组临床总有效率为93.85%(61/65),高于对照组的78.46%(51/65),(P0.05)。治疗后,两组患者腓总神经、正中神经的运动神经传导速度(MNCV)、感觉神经传导速度(SNCV)均高于治疗前,观察组高于对照组,组间比较差异显著(P0.05)。治疗后,两组患者TCSS、VAS评分、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、C-反应蛋白(CRP)低于治疗前,观察组低于对照组,组间比较差异明显(P0.05)。观察组不良反应发生率为13.85%(9/65),对照组为7.69%(5/65),组间相比差异不明显(P0.05)。结论:α-硫辛酸与前列地尔联合治疗糖尿病周围神经病变,疗效满意,可显著改善患者的神经症状,降低炎症因子水平,且用药安全性好,值得在临床上进一步推广使用。     

神经节苷脂联合咪达唑仑治疗重症颅脑损伤的临床疗效及对患者血清MMP-9、GFAP、MBP、NSE水平的影响

目的:探讨神经节苷脂联合咪达唑仑治疗重症颅脑损伤的临床疗效及对患者血清基质金属蛋白酶-9(MMP-9)、胶质纤维酸性蛋白(GFAP)、髓鞘碱性蛋白(MBP)、神经元特异性烯醇化酶(NSE)水平的影响。方法:选择2016年3月到2017年9月于我院进行治疗的85例重症颅脑损伤患者,将其按随机数表法分为观察组(n=45)和对照组(n=40),对照组使用神经节苷脂治疗,观察组采用神经节苷脂联合咪达唑仑治疗。比较两组治疗后疗效及血清GFAP、中枢神经特异蛋白(S100β)、NSE、MMP-9、MBP、C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)水平、格拉斯哥昏迷评分(Glasgow Coma Scale,GCS)评分的变化及不良反应的发生情况。结果:治疗后,观察组临床疗效总有效率(93.33%)显著高于对照组(75.00%,P0.05);两组血清GFAP、S100β、NSE、MMP-9、MBP、CRP、IL-6及TNF-α水平均较治疗前明显下降,且观察组以上指标均显著低于对照组(P0.05);观察组GCS评分明显高于对照组(P0.05),且不良反应发生率明显低于对照组(6.67%vs. 30.00%,P0.05)。结论:神经节苷脂联合咪达唑仑治疗重症颅脑损伤患者的临床效果显著,明显优于单用神经节苷脂治疗,可能与其有效改善患者血清MMP-9、GFAP、MBP、NSE水平及抑制炎症因子的生成有关。     

度洛西汀联合硫辛酸治疗糖尿病周围神经病变的疗效观察

目的观察度洛西汀联合硫辛酸治疗糖尿病周围神经病变(DPN)的临床疗效及其安全性。方法将90例糖尿病周围神经病变患者随机分为治疗组(45例)与对照组(45例),两组均给予硫辛酸(600mg)静脉滴注,治疗组同时口服度洛西汀(60mg),观察比较两组患者的临床疗效以及治疗前后视觉模拟评分(VAS)、不良反应情况。结果治疗后,两组患者的疼痛情况均有明显改善,治疗组总有效率为86.7%明显优于对照组的48.9%,差异有统计学意义(P0.05);治疗后,治疗组的视觉模拟评分(VAS)明显低于对照组(P0.05)。结论度洛西汀联合硫辛酸治疗糖尿病周围神经病变的效果理想,且安全性高。     

神经节苷脂联合高压氧治疗颅脑外伤的临床研究

目的探讨神经节苷脂联合高压氧治疗颅脑外伤的临床效果。方法选取2015年1月~2017年1月我院收治的1000例颅脑外伤患者作为研究对象,随机分为对照组和观察组各500例,对照组给予常规治疗,观察组在对照组的基础上联合高压氧和神经节苷脂治疗,分析比较两组的临床效果。结果观察组的治疗有效率显著高于对照组,组间差异有统计学意义(P0.05)。观察组的病死率明显低于对照组,差异具有统计学意义(P0.05)。结论高压氧联合神经节苷脂治疗颅脑外伤的效果显著,有利改善患者的预后,降低病死率,值得临床应用。     

低频电刺激联合间歇导尿及Motomed运动训练对脊髓损伤致神经源性膀胱患者膀胱内压力及膀胱容量的影响

目的:探讨低频电刺激联合间歇导尿及Motomed运动训练对脊髓损伤致神经源性膀胱患者膀胱内压力及膀胱容量的影响。方法:选取我院2015年12月～2018年2月收治的脊髓损伤致神经源性膀胱患者92例,根据随机数字表法将其分为对照组(n=46)与研究组(n=46)。两组均给予间歇性导尿、盆底肌训练、膀胱功能训练等常规干预,对照组在此基础上采取低频电刺激,研究组于对照组基础上采取Motomed运动训练,两组均干预2个月。比较两组的临床疗效、治疗前及治疗2个月后的排尿情况(日均单次排尿量、日单次最大排尿量、日均排尿次数)、尿动力学情况(最大尿流率、膀胱容量、残余尿量、膀胱内压力)、LUTS(国际下尿路症状评分)及USDS(泌尿症状困扰评分)。结果:治疗后,研究组总有效率(93.48%)显著高于对照组(78.26%)(P0.05);治疗2个月后,两组日均单次排尿量、日单次最大排尿量、日均排尿次数、最大尿流率、膀胱容量、膀胱内压力均较治疗前显著增多,且研究组以上指标均明显高于对照组(P0.05);两组LUTS及USDS分值均较治疗前显著降低,且研究组以上指标均显著低于对照组(P0.05)。结论:间歇导尿联合低频电刺激与Motomed运动训练可有效改善脊髓损伤致神经源性膀胱患者尿动力学状态及排尿情况,增大膀胱容量及膀胱内压力等,缓解下尿路症状及泌尿症状困扰程度,提高治疗效果。     

神经节苷脂钠联合高压氧治疗突发性耳聋患者的效果评估

目的:探讨神经节苷脂钠联合高压氧治疗突发性耳聋患者的疗效,并分析其对患者血清高迁移率蛋白-1(High mobility protein-1,HMGB1)、中性粒细胞激活肽-78(Neutrophil activating peptide-78,ENA-78)的影响。方法:选择我院2018年1月至2019年8月接诊的96例突发性耳聋患者,通过随机数表法将其分为观察组和对照组,每组48例。对照组在常规治疗基础上给予高压氧治疗,观察组在对照组的基础上给予神经节苷脂钠注射液治疗,两组均连续治疗2个疗程。治疗后,比较两组的临床疗效、治疗前后纯音听阈测试结果、凝血功能、血清HMGB1、ENA-78水平的变化及不良反应的发生情况。结果:治疗2个疗程后,观察组临床疗效总有效率明显高于对照组(93.75%vs79.17%),差异有统计学意义(P0.05);观察组纯音听阈测试结果明显低于对照组[(32.14±4.94)dB vs.(37.23±5.12)dB](P0.05),凝血酶原时间(Prothrombin time,PT)、部分活化凝血酶原时间(Partial activated prothrombin time,APTT)、凝血酶时间(Thrombin time,TT)明显短于对照组,纤维蛋白原(Fibrinogen,FIB)明显低于对照组。结论:神经节苷脂钠联合高压氧治疗突发性耳聋患者的效果显著优于单用高压氧治疗,其可有效促进听力恢复,且不增加药物不良反应,其机制可能与降低血清HMGB1、ENA-78水平有关。     

单唾液酸四己糖神经节苷脂钠治疗急性期脑出血的临床分析

目的：观察分析单唾液酸四己糖神经节苷脂钠治疗急性期脑出血的临床疗效,总结其临床用药经验。方法：选取我院2010年7月至2012年7月急性期脑出血的患者86例,按照数字表随机抽取法分成2组,对照组43例使用常规治疗,观察组43例在常规治疗基础上,加用单唾液酸四己糖神经节苷脂钠治疗,观察对比两组的临床治疗效果。结果：观察组治疗后总有效率为93．0％（40／43）对照组治疗后总有效率为76．8％（33／43）,两组治疗效果对比差异明显（P〈0．05）,具有统计学意义。结论：单唾液酸四己糖神经节苷脂钠治疗急性期脑出血的临床疗效显著,优于常规治疗,可有效保护神经功能不受损。     

α-硫辛酸联合依帕司他对糖尿病周围神经病变患者血糖、神经传导速度及血清炎症因子的影响

摘要 目的：探讨α-硫辛酸联合依帕司他对糖尿病周围神经病变（DPN）患者血糖、神经传导速度及血清炎症因子的影响。方法：选取2016年7月~2019年12月期间我院收治的DPN患者460例,按随机数字表法将上述患者分为对照组（n=230）和研究组（n=230）,对照组患者予以依帕司他治疗,研究组则在对照组的基础上联合α-硫辛酸治疗,比较两组患者疗效、血糖、神经传导速度、血清炎症因子及不良反应。结果：研究组治疗2个月后的临床总有效率为86.09%（198/230）,高于对照组的69.13%（159/230）（P<0.05）。两组治疗2个月后空腹血糖（FPG）、餐后2 h血糖（2hPG）均下降,且研究组低于对照组（P<0.05）。两组治疗2个月后正中神经运动神经传导速度 ( MCV) 和感觉神经传导速度( SCV)及腓总神经MCV、SCV均升高,且研究组高于对照组（P<0.05）。两组治疗2个月后白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、超敏-C反应蛋白（hs-CRP）均下降,且研究组低于对照组（P<0.05）。两组不良反应发生率比较差异无统计学意义（P>0.05）。结论：α-硫辛酸联合依帕司他治疗DPN患者,疗效显著,可有效降低血糖,改善神经传导速度及血清炎症因子水平,且安全性较好。     

Early lipoic acid intake protects retina of diabetic mice

The aim of this study was to test the effect of lipoic acid treatment on the retina after a short diabetic insult. Diabetes was induced by alloxan and mice were divided into sub-groups; control, diabetic, diabetic+insulin and all groups received±lipoic acid (100 mg/kg body weight) for 3 weeks. GSH content, MDA concentration, GPx activity were measured and electroretinograms (ERG) were recorded. Early administration of lipoic acid to diabetic mice prevented the statistically significant decreases of GSH content and GPx activity and normalized MDA concentration. Moreover, lipoic acid restored electroretinogram b-wave amplitude of diabetic animals to control values. Lipoic acid has a protective effect on the diabetic retina.     

Early lipoic acid intake protects retina of diabetic mice

The aim of this study was to test the effect of lipoic acid treatment on the retina after a short diabetic insult. Diabetes was induced by alloxan and mice were divided into sub-groups; control, diabetic, diabetic+insulin and all groups received+/-lipoic acid (100 mg/kg body weight) for 3 weeks. GSH content, MDA concentration, GPx activity were measured and electroretinograms (ERG) were recorded. Early administration of lipoic acid to diabetic mice prevented the statistically significant decreases of GSH content and GPx activity and normalized MDA concentration. Moreover, lipoic acid restored electroretinogram b-wave amplitude of diabetic animals to control values. Lipoic acid has a protective effect on the diabetic retina.     

针刺联合生物反馈治疗脊髓损伤后神经源性膀胱的疗效观察

目的:探讨针刺联合生物反馈治疗脊髓损伤后神经源性膀胱的治疗效果。方法:将2016年6月到2018年1月来我院就诊的脊髓损伤所致神经源性膀胱患者50例随机分成对照组和治疗组,每组25例。对照组予患者实施生物反馈治疗,治疗组予患者实施生物反馈联合针刺治疗。以上两组患者均实行基础的康复训练、清洁间歇导尿及反射性排尿训练,并实行定时定量的饮水计划。分别于治疗前后行尿流动力学检查比较患者的膀胱内压力、残余尿量,记录患者的日排尿次数、最大排尿量以及患者的LUTS(Lower urinary tract symptoms)评分。结果:治疗后,对两组患者的治疗有效率、最大排尿量、日排尿次数、残余尿量、膀胱内压力以及LUTS评分的数据进行对比,治疗组的效果明显优于对照组(p0.05)。结论:针刺联合生物反馈治疗脊髓损伤所致神经源性膀胱的效果更佳。     

Beneficial effects of alpha-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress.

The impairment of nitric oxide (NO)-mediated vasodilation in diabetes has been attributed to increased vascular oxidative stress. Lipoic acid has been shown to have substantial antioxidative properties. The aim of this study was to assess the effect of lipoic acid on NO-mediated vasodilation in diabetic patients in comparison with the well-recognized effect of ascorbic acid. Using venous occlusion plethysmography, we examined the effects of lipoic acid (0.2 mM) and ascorbic acid (1 and 10 mM) on forearm blood flow responses to acetylcholine, sodium nitroprusside and concomitant infusion of the NO-inhibitor, N(G)-monomethyl-L-arginine, in 39 diabetic patients and 11 control subjects. Plasma levels of antioxidants and parameters of lipid peroxidation were measured and correlated to endothelial function tests. Lipoic acid improved NO-mediated vasodilation in diabetic patients, but not in controls. NO-mediated vasodilation was improved by ascorbic acid at 10 mM, but not 1 mM. Improvements of endothelial function by ascorbic acid and lipoic acid were closely related. The beneficial effects of lipoic acid were positively related to plasma levels of malondialdehyde and inversely related to levels of ubiquinol-10. These findings support the concept that oxidative stress contributes to endothelial dysfunction and suggest a therapeutic potential of lipoic acid particularly in patients with imbalance between increased oxidative stress and depleted antioxidant defense.     

The role of lipoic acid residues in the pyruvate dehydrogenase multienzyme complex of Escherichia coli.

Two lipoic acid residues on each dihydrolipoamide acetyltransferase (E2) chain of the pyruvate dehydrogenase multienzyme complex of Escherichia coli were found to undergo oxidoreduction reactions with NAD+ catalysed by the lipoamide dehydrogenase component. It was observed that: (a) 2 mol of reagent/mol of E2 chain was incorporated when the complex was incubated with N-ethylmaleimide in the presence of acetyl-SCoA and NADH; (b) 4 mol of reagent/mol of E2 chain was incorporated when the complex was incubated with N-ethylmaleimide in the presence of NADH; (c) between 1 and 2 mol of acetyl groups/mol of E2 chain was incorporated when the complex was incubated with acetyl-SCoA plus NADH; (d) 2 mol of acetyl groups/mol of E2 chain was incorporated when the complex was incubated with pyruvate either before or after many catalytic turnovers through the overall reaction. There was no evidence to support the view that only half of the dihydrolipoic acid residues can be reoxidized by NAD+. However, chemical modification of lipoic acid residues with N-ethylmaleimide was shown to proceed faster than the accompanying loss of enzymic activity under all conditions tested, which indicates that not all the lipoyl groups are essential for activity. The most likely explanation for this result is an enzymic mechanism in which one lipoic acid residue can take over the function of another.     

Natural occurrence of ganglioside lactones. Isolation and characterization of GD1b inner ester from adult human brain

A new ganglioside containing an inner ester linkage was extracted from adult brain specimens, obtained at the time of surgery on 51-70-year-old subjects, purified, and analyzed. It contains glucose, galactose, N-acetylgalactosamine, an N-acetylneuraminic acid in the molar ratio 1:2:1:2, but, on ion-exchange chromatography, behaves as a monosialoganglioside. Structural analyses showed its basic neutral glycosphingolipid core to be ganglio-N-tetraose ceramide, carrying a disialosyl residue on the 3-position of internal galactose. Sialidase degradation and chemical analysis of the products obtained after alkaline treatments suggested one sialic acid residue to be involved in an ester linkage. Fast atom bombardment-mass spectrometry indicated the presence of an inner ester linkage between the carboxyl group of the external sialic acid residue and a hydroxyl group of the internal one. On these bases, the new ganglioside can be assumed to be a GD1b in lactonic form. This ganglioside is present only in trace amounts in the brain of infants, but its content increases with age, reaching a value of 3.5% of total sialic acid in 51-70-year-old subjects.     

Kinetic analysis of the role of lipoic acid residues in the pyruvate dehydrogenase multienzyme complex of Escherichia coli

The catalytic roles of the two reductively acetylatable lipoic acid residues on each lipoate acetyltransferase chain of the pyruvate dehydrogenase complex of Escherichia coli were investigated. Both lipoyl groups are reductively acetylated from pyruvate at the same apparent rate and both can transfer their acetyl groups to CoASH, part-reactions of the overall complex reaction. The complex was treated with N-ethylmaleimide in the presence of pyruvate and the absence of CoASH, conditions that lead to the modification and inactivation of the S-acetyldihydrolipoic acid residues. Modification was found to proceed appreciably faster than the accompanying loss of enzymic activity. The kinetics of the modification were fitted best by supposing that the two lipoyl groups react with the maleimide at different rates, one being modified at approximately 3.5 times the rate of the other. The loss of complex activity took place at a rate approximately equal to that calculated for the modification of the more slowly reacting lipoic acid residue. The simplest interpretation of this result is that only this residue is essential in the overall catalytic mechanism, but an alternative explanation in which one lipoic acid residue can take over the function of another was not ruled out. The kinetics of inactivation could not be reconciled with an obligatory serial interaction between the two lipoic acid residues. Similar experiments with the fluorescent N-[p-(benzimidazol-2-yl)phenyl]maleimide supported these conclusions, although the modification was found to be less specific than with N-ethylmaleimide. The more rapidly modified lipoic acid residue may be involved in the system of intramolecular transacetylation reactions that couple active sites in the lipoate acetyltransferase component.     

Preparation of GM1 ganglioside molecular species having homogeneous fatty acid and long chain base moieties

A new procedure is described for preparing the molecular species of GM1 ganglioside that carry a single fatty acid (myristic (C14:0), stearic (C18:0), arachidic (C20:0) or lignoceric (C24:0) acid) and a single long chain base (C18 or C20 sphingosine, C18 or C20 sphinganine, each of them in natural 3D(+)erythro or unnatural 3L(-)threo form). The procedure consisted of the following steps: a) alkaline hydrolysis of GM1 ganglioside in the presence of tetramethylammonium hydroxide, which produces de-N-acylation of the ceramide and de-N-acetylation of the sialic acid residue; b) specific re-N-acylation at the long chain base amino group with a new fatty acid (myristic, stearic, arachidic, or lignoceric) in the presence of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride; and c) final re-N-acetylation at the level of the sialic acid residue. GM1 ganglioside molecular species, completely homogeneous in the ceramide portion, were prepared by reversed phase high performance liquid chromatography. The GM1 ganglioside molecular species were analyzed for saccharide, fatty acid, and long chain base composition by chemical and spectrometric analyses. Using a combination of the two procedures, 32 different molecular species of GM1 ganglioside, over 99% homogeneous, have been prepared.     

Chicken liver H-protein, a component of the glycine cleavage system. Amino acid sequence and identification of the N epsilon-lipoyllysine residue

The complete amino acid sequence of H-protein from chicken liver was determined by aligning peptides obtained by cyanogen bromide, endoproteinase Lys-C, Staphylococcus aureus V8 protease, and chymotrypsin cleavage together with the partial NH2- and COOH-terminal sequence of the intact protein. H-protein consists of 125 amino acids and a lipoic acid moiety linked to lysine 59. The sequence is: (sequence in text). The lysyl residue involved in lipoic acid attachment is indicated with an asterisk. The molecular weight including lipoic acid is calculated to be 13,883. From the secondary structure predicted by the method of Chou and Fasman (Chou, P. Y., and Fasman, G. D. (1978) Adv. Enzymol. 47, 45-148) the lipoic acid binding region shows alpha-helical structure and is predicted to be an interior portion of the protein from the hydropathic profile according to Kyte and Doolittle (Kyte, J., and Doolittle, R. F. (1982) J. Mol. Biol. 157, 105-132).