地塞米松对利多卡因神经毒性的保护作用

目的 观察地塞米松(Dex)对利多卡因(Lido)诱导小鼠神经母细胞瘤细胞株(N2a)毒性的影响.方法 用0、100、250、500、1 000和1 500 μmol/L Lido孵化N2a细胞9 h后,将细胞分为对照(Con)组、Lido组、Dex组和Dex+Lido组.观察细胞形态学变化,并检测细胞凋亡率和细胞Akt磷酸化水平.结果 (1)与0 μmol/L Lido 比较,100、250和500 μmol/L Lido未引起明显细胞形态学变化,而1 000和1 500 μmol/L Lido引起显著细胞损伤;100和250 μmol/L Lido未引起明显的细胞凋亡增加,而500、1 000、1 500 μmol/L Lido分别引起轻度、中度和重度细胞凋亡(P<0.01).(2)Dex+Lido组核固缩率显著低于Lido组(P<0.01).(3)Dex+Lido组N2a细胞中Akt磷酸化水平显著高于IAdo组(P<0.01).结论 Lido呈浓度依赖性地诱导N2a细胞损伤,Dex预处理显著减轻Lido所致的细胞损伤,其保护机制与抑制Lido诱导的Akt脱磷酸化有关.     

利多卡因对脑氧耗和脑血管功能的影响

目的 观察人体静注利多卡因对脑氧耗和脑血管功能的影响。方法 ２０例颅脑手术病人，麻醉前经颈内静脉和桡动脉穿刺置入导管，在静注２％利多卡因１．５ｍｇ／ｋｇ前后２分钟分别从导管中取动，静脉血标本检测血气。并用ＨＮＣＰＡ－２脑血管功能检测仪记录双侧颈内动脉和椎动脉的分钟血流量，血流入时间和血管转折高比率。     

地塞米松联合碱化利多卡因膀胱灌注治疗氯胺酮相关性膀胱炎的疗效观察

【摘要】 目的 观察地塞米松联合碱化利多卡因膀胱灌注治疗氯胺酮相关性膀胱炎的疗效。方法 8例确诊为氯胺酮相关性膀胱炎经戒断吸食氯胺酮、抗生素治疗等常规治疗无效,而拒绝行膀胱水灌注及注射肉毒素的男性患者,用地塞米松及碱化利多卡因行规律膀胱灌注,比较治疗前及治疗1周及3周后患者的排尿情况、OABSS评分等症状改善情况。 结果 8例患者经治疗后症状明显改善,排尿日记显示治疗1周后患者日间排尿次数由(20.5±7.8)次减至(5.6±2.3)次(P<0.05),夜间排尿次数由(15.5±3.2)次减少至(3±1.2)次(P<0.05),尿量由(30.4±12.4)mL/次增加至(50±10.1)mL/次(P<0.05)。OABSS评分由治疗前的(10.7±1.5)分减至治疗后的(5.2±1.3)分(P<0.05)。8例患者均未出现药物不良反应。 结论 地塞米松联合碱化利多卡因膀胱灌注治疗氯胺酮相关性膀胱炎安全、药物普及且费用低,在短期内是有效的,对拒绝行手术治疗的患者,可考虑使用。     

消炎痛对腹主动脉瘤Ⅳ型胶原酶活性的影响

手术是治疗腹主动脉瘤 (ＡＡＡ)的有效方法 ,但对于那些小的甚至是无症状的ＡＡＡ暂不需手术 ,却又不能任其发展 ,故近年来寻求药物治疗途径抑制Ⅳ型胶原酶的分泌 ,以达到阻止ＡＡＡ的发生、发展的目的。本实验研究消炎痛对ＡＡＡ中Ⅳ型胶原酶的作用 ,以探讨其临床应用价值。材料与方法1.实验动物及分组 :选用Ｗｉｓｔａｒ大鼠 2 4只 (由中国医科大学实验动物部提供 ) ,体重 2 5 0～ 30 0ｇ,随机分两组 ,每组为12只 ,消炎痛组 :术后用消炎痛 1 6ｍｇ每日皮下注射 ,至术后7ｄ处死。盐水对照组 :皮下注射等量生理盐水。2 动物模型建立 :Ｗｉ…     

利多卡因联合地塞米松治疗甘露醇外渗损伤的实验研究

目的 探讨利多卡因联合地塞米松局部封闭治疗20%甘露醇外渗4 h后局部损伤的效果.方法 将7只小白鼠四肢内侧制成20%甘露醇外渗模型.4 h后,随机抽取1只小白鼠于四肢注射部位取材(E组),观察甘露醇外渗致局部组织损伤情况;其余6只按模型部位分为A组(左上肢),B组(左下肢)、C组(右上肢)及D组(右下肢).A组予2%利多卡因2 ml加地塞米松1 mg局部封闭,B组予2%利多卡因2 ml局部封闭,C组予生理盐水局部封闭,D组为空白对照.处理24 h后取材进行病理学观察.结果 光学显微镜观察显示,E组局部组织损伤呈重度表现;A组呈无或轻度表现,轻于B组、C组、D组和E组;B组以中度为主,轻于C组、D组(均呈重度)和E组.结论 甘露醇外渗后4 h组织损伤严重,外渗后需及时采取有效措施,避免组织损伤加重;利多卡因联合地塞米松封闭治疗甘露醇外渗4 h形成的局部组织损伤快速、简便并安全有效.     

利多卡因对实验性哮喘豚鼠的作用及机制

目的　观察雾化吸入利多卡因对实验性哮喘豚鼠的影响 ,并初步探讨其机制。方法　32只豚鼠随机分为四组 ,每组 8只 :正常组 (C组 )、哮喘组 (A组 )、地塞米松治疗组 (D组 )和利多卡因治疗组 (L组 )。采用卵蛋白致敏和激活制成豚鼠哮喘模型 ,观察各组的诱喘时间及血清和肺灌洗液中一氧化氮 (NO)水平的变化。结果　各治疗组诱喘时间均比哮喘组长。A组血清NO显著高于C组 (P <0 0 5 ) ;与A组相比 ,D组显著降低 (P <0 0 5 ) ,L组无明显差异。肺泡灌洗液中NO值A组较C组明显升高 (P <0 0 5 ) ;与A组比较 ,D组和L组均明显降低 (P <0 0 5 )。结论　雾化吸入利多卡因对实验性哮喘豚鼠有治疗作用 ,这可能与其抑制局部NO的合成有关     

封闭负压引流技术对人慢性创面中胶原酶活性的影响

目的研究人慢性创面经封闭负压引流（vacuum—assisted closure，VAC）治疗前后，创面渗出液中胶原酶活性的变化，以部分阐明VAC促进慢性创面愈合的机理。方法取4例急性创面在术后1、2、3d的创面引流液（乳癌术后），同时收集6例慢性创面（4例静脉性溃疡，2例压力性溃疡）在VAC治疗前以及治疗后2、4、6d的创面渗出液，利用酶谱分析的方法，观察各时间点的渗出液对可溶性Ⅲ型胶原的降解情况，同时应用强力霉素抑制实验来分析渗出液中胶原酶的类型。结果急性创面引流液可以部分降解Ⅲ型胶原，随时间推移变化较小，慢性创面渗出液中的胶原酶活性较高，VAC治疗前基本将Ⅲ型胶原全部降解，随时间推移、降解减少，胶原酶活性下降，强力霉素抑制实验证明在100μmol／L浓度时无抑制，在600μmol／L浓度时出现部分抑制。结论在慢性创面渗出液中胶原酶活性增高，VAC的应用可以降低胶原酶的活性，阻止胶原蛋白大量降解，利于创面愈合，在慢性创面渗出液中胶原酶应主要是MMP-1型（成纤维细胞型）。     

利多卡因对颅内压的影响

观察１０例患者静脉注射利多卡因２ｍｇ／ｋｇ后颅内压的变化。结果显示：８例在１～２分钟内降低０．１３～０．５３ｋＰａ，持续时间５～１２分钟；另２例上升０．１３ｋＰａ，持续１～２分钟。患者年龄越轻，下降幅度越大。认为利多卡因致颅内压快速下降的原因可能与其直接收缩脑血管有关。     

在体外乳鼠心肌细胞缺氧的损伤及利多卡因的保护作用

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腰椎组织胶原酶活性测定及临床意义

目的研究腰椎黄韧带，正常和突出的椎间盘髓核胶原酶活性变化与组织退变的关系。方法 用＾３Ｈ－可溶性胶原底物标记法对１１例黄韧带，３４例正常椎间盘髓核和３５例椎间盘突出症髓核的胶原酶活性进行测定。结果 受测腰椎组织胶原酶活性为：黄韧带〈正常椎间盘髓核〈突出椎间盘髓核，３种组织之间测定值差异有显著性。     

汉防己甲素对增生性瘢痕基质胶原酶活性的影响

目的观察汉防己甲素对瘢痕胶原酶活性的影响，进一步阐明其抗瘢痕作用的机理。方法将汉防己甲素的实验浓度控制在低于细胞增殖抑制范围之内，采用加胶原蛋白底物的SDS—PAGE电泳法分离胶原酶，胰蛋白酶激活后利用湿胶密度扫描仪分析胶原酶的活性。同时采用改良的氯胺T法测量细胞外胶原蛋白量，并分析两者的相关关系。结果在不抑制细胞增殖的情况下，汉防己甲素可显著提高胶原酶的活性，使细胞外胶原蛋白减少，两者呈显著的负相关，此作用强于激素。结论增强胶原酶降解胶原蛋白的活性，减少细胞外胶原沉积是汉防己甲素抗瘢痕作用机理之一。     

人体正常皮肤及增生性瘢痕胶原酶活性的检测

为探讨胶原降解代谢在增生性瘢痕形成中的作用,对23例患增生性瘢痕的成年病人的瘢痕组织(其中8例经病理检查)及正常皮肤的胶原酶活性作了检测和比较观察。检测结果:瘢痕组织的胶原酶活性平均值为197.09±48.10(U),正常皮肤胶原酶活性平均值为73.17±13.71(U),二者差异有非常显著意义(P<0.01)。表明增生性瘢痕的形成不仅与胶原的过度合成与沉积有关,同时与胶原降解代谢减少有关。     

The influence of bacterial collagenase on regeneration of severed rat sciatic nerves

Summary Regeneration of peripheral nerve fibers is impeded by the formation of scar tissue at the site of injury. The possible beneficial effect of collagenase on nerve regeneration was studied using clinical, neurophysiological (evoked potentials) and histological (nerve fiber counts) methods.The sciatic nerves of rats were transected and the severed ends abutted and sewn together. In one series, the area about the lesion was covered with fibrin adhesive and infused with either isotonic saline (controls) or collagenase (treatment group). In the other series, the severed ends of the nerve were inserted into a silicone tube and separated by a collagen plug, which was infused with either saline or collagenase. Compared to the controls, the treated animals showed a significant improvement of clinical and neurophysiological parameters. After 3 months of observation, the collagen content of the transection site was reduced, and in the silicone series, the total number of myelinated axons 5mm distal to the site of transection was increased, while the fiber diameter distribution was unchanged.Supported by a grant from the Deutsche Forschungsgemeinschaft (We 1248).     

The further purification and characterization of mouse bone collagenase

Mouse bone collagenase, a specific tissue collagenase, was isolated from the tissue culture media of 5 day old mouse tibiae. By a combination of (NH₄)₂SO₄ precipitation, molecular sieve filtration and ion exchange chromatography a fraction was obtained with a yield of approximately 11% which had a specific enzyme activity 120-fold greater than the original crude extract. The molecular weight of the fraction containing the enzyme activity was approximately 41000 as determined by calibrated molecular sieve filtration studies. There were at least two distinct major fractions and one minor fraction possessing collagenase activity which had distinct isoelectric points. It is not clear whether these fractions represent isoenzymes from bone or from bone and cartilage, or are derived from a single enzyme which has been minimally degraded by the extraction and purification techniques used. Collagenase activity was inhibited by EDTA, cysteine and horse serum, but not by phenylmethylsulfonylfluoride, epsilon amino caproic acid or soybean trypsin inhibitor.

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Zusammenfassung Mäuseknochen-Kollagenase, eine spezifische Gewebe-Kollagenase, wurde aus Gewebekulturmedien von 5 Tage alten Mäusetibiae isoliert. Durch eine Kombination von (NH₄)₂SO₄-Ausfällung, Gelfiltration und Ionenaustausch-Chromatographie wurde mit ungefähr 11% Ausbeute eine Fraktion erhalten, die eine spezifische Enzymaktivität besaß, welche 120mal größer war als diejenige des ursprünglichen unbehandelten Extraktes. Das Molekulargewicht der die Enzymaktivität enthaltenden Fraktion war ungefähr 41000, was durch kalibrierte Gelfiltrations-Untersuchungen bestimmt wurde. Mindestens zwei verschiedene Hauptfraktionen und eine kleinere Fraktion mit Kollagenaseaktivität wurden erhalten, welche verschiedene isoelektrische Punkte hatten. Es ist unklar, ob diese Fraktionen Isoenzyme aus Knochen oder aus Knochen und Knorpel darstellen, oder ob sie von einem einzelnen Enzym stammen, welches durch die verwendeten Extraktions- und Reinigungstechniken minimal degradiert wurde. Die Kollagenaseaktivität wurde durch EDTA, Cystein und Pferdeserum gehemmt, nicht aber durch Phenylmethylsulfonylfluorid, Epsilon-amino-capronsäure oder Soyabohnen-Trypsin-Hemmer.

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Résumé De la collagénase osseuse de souris, une collagénase tissulaire spécifique, est isolée du milieu de culture tissulaire d'un tibia de souris de 5 jours. En combinant une précipitation de (NH₄)₂SO₄, une filtration moléculaire sur tamis et la chromatographie par échangeurs d'ions, on obtient une fraction d'un rendement d'environ 11%, qui possède une activité enzymatique spécifique 120 fois plus élevée que l'extrait original total. Le poids moléculaire de la fraction, contenant l'activité enzymatique, est d'environ 41000, en se basant sur des études de filtration par tamis moléculaire calibré. Il existe au moins deux fractions principales distinctes et une fraction plus faible, ayant des activités en collagénase et des points isoélectriques distincts. Il n'est pas démontré que ces fractions constituent des isoenzymes de l'os ou de l'os et du cartilage, ou sont dérivés d'une seule enzyme, peu dégradée par l'extraction et la purification. L'activité de la collagénase est inhibée par l'EDTA, la cystéine, le sérum de cheval; mais elle résiste au fluorure de phénylméthyle-sulfonyle, à l'acide epsilon aminocaproique et à l'inhibiteur de trypsine de graine de soja.

     

A comparison of glucose-free 2% lidocaine and hyperbaric 5% lidocaine for spinal anaesthesia

Fifty patients scheduled to undergo transurethral surgery of the bladder were allocated to receive spinal anaesthesia with either glucose-free 2% lidocaine (80 mg) or hyperbaric 5% lidocaine (80 mg). Onset time, cephalad spread of analgesia, duration of analgesia, duration and intensity of motor block, quality of analgesia, and the patients' ability to walk 5 m and to micturate postoperatively were assessed. Onset and spread of analgesia were fast and comparable in the two groups. At 60 min, the median segmental level of analgesia was T9 and T10 for the 2% and the 5% group, respectively, allowing transurethral surgery to be performed for at least 1 h. In the 2% group the motor block was more pronounced and longer lasting than in the 5% group. Two patients in the 5% group needed general anaesthesia because of pain. The time from injection of the spinal anaesthetic until the patients were able to walk 5 m and to micturate was equal in the two groups, and 89% of all the patients were able to walk and micturate within 4 h. It is concluded that spinal anaesthesia with 80 mg and 2% or 5% lidocaine provides analgesia for transurethral surgery and is characterized by fast recovery of motor and detrusor function.     

Effect of a calcium-channel blocker (verapamil) on the morphology, cytoskeleton and collagenase activity of human skin fibroblasts

The effects of verapamil modulating collagen biosynthesis have prompted us to study the role of this drug in cultured fibroblasts. In this article, we describe the effects of verapamil on fibroblast behaviour, with special emphasis to phenotypic modifications, reorganisation of actin filaments and secretion of MMP1. Human dermal fibroblasts treated with 50-μM verapamil changed their normal spindle-shaped morphology to stellate. Treated cells showed discrete reorganisation of actin filaments, as revealed by fluorescein isothiocyanate (FITC)-phalloidin staining and confocal microscopy. We hypothesised that these effects would be associated to lower levels of cytosolic Ca²⁺. Indeed, short time loading with calcium green confirmed that verapamil-treated fibroblasts exhibited lower intracellular calcium levels compared to controls. We also observed that verapamil increases the secretion of MMP1 in cultured fibroblasts, as demonstrated by zymography, specific substrate assays and immunoblot. The morphological alterations induced by verapamil are neither cytotoxic nor associated with other dramatic cytoskeleton alterations. Thus we may conclude that this drug enhances collagenase secretion and does not disrupt the major tracks necessary to deliver these enzymes in the extracellular space. The present results suggested that verapamil could be used at physiological levels to enhance collagen I breakdown, and may be considered a potential candidate for intralesional therapy of wound healing and fibrocontractive diseases.