The lead-chelating effects of substituted dithiocarbamates

The effectiveness of certain substituted dithiocarbamates in mobilizing lead from preexposed rats was investigated. The animals received 10 mg Pb/kg/day, intragastrically, for 8 weeks and were treated thereafter with 400 mumol/kg, intraperitoneally, of morpholine dithiocarbamate, tetraammonium ethylenediamine diacetic acid dithiocarbamate (EDDTC), ammonium diethanolamine dithiocarbamate (ADDTC), sodium diethyldithiocarbamate, N-benzyl-D-glucamine dithiocarbamate (NBGDTC), or dimercaptosuccinic acid, daily for 5 days. All the chelating agents were effective in lowering the hepatic and renal burden of Pb. ADDTC, EDDTC, and NBGDTC were also able to lower the long bone Pb content. The lowering of Pb burden had no relationship to restoration of Pb-induced hematopoietic alterations. The relatively lower lipophilicity of substituted dithiocarbamates, owing to the presence of hydrophilic groups, seems to be advantageous in preventing passage of metal chelate into the brain. None of the substituted dithiocarbamates caused excessive excretion of urinary Cu and Zn. ADDTC and EDDTC appear to be promising in the management of Pb poisoning.     

Influence of CaNa2 EDTA on topical 5-aminolaevulinic acid photodynamic therapy

Background We asssessed whether the CaNa2 EDTA could improve the accumulation of protoporphyrin Ⅸ (PpⅨ) and photosensitisation in HEp-2 cells as well as the depth of treatment of skin cancers on the topical 5-Aminolaevulinic acid (5-ALA) PDT.Methods HEp-2 cells were incubated with 5-ALA (0-1mmol/L) and CaNa2EDTA (0-1mmol/L) for 4 hours, intracellular protoporphyrin Ⅸ content was quantified by extraction, and cell viability was assessed by use of the methyl-tetrazolium (MTT) assay four hours after exposure to light. In comparison with the pictures before and after treatment, depth of treatment could be determined using a Acuson Sequioa 512 phase-array system in paired experiments.Results PpⅨ accumulation increased with increasing extracellular concentrations of ALA (0-1mmol/L). Adding 1mmol/L of CaNa2EDTA increased 30% PpⅨ accumulation over the same period of incubation in the concentration of 1mmol/L ALA. Significant difference was observed between the 5-ALA alone group and 5-ALA combined CaNa2 EDTA group in the PpⅨ accumulation (P<0.01). Cell viability after exposure to light decreased with adding CaNa2 EDTA, a statistical difference in a same fluence above 1.2 J/cm2 between two groups was demonstrated (P<0.05, P<0.01 respectively). Depth of treatment of skin cancers were increased in CaNa2 EDTA-treated group.Conclusion CaNa2 EDTA could improve the PpⅨ accumulation and photosensitisation in HEp-2 cells. Clinically, CaNa2 EDTA could increase the depth of treatment in the cutaneous cancers.     

六种金属中毒解毒药治疗肝豆状核变性的临床研究

目的　探讨金属中毒解毒药治疗肝豆状核变性 (HLD)的临床应用价值。方法　将 85 2例HLD随机分为还原型谷胱甘肽组 (GSH组 )、二巯基丁二钠组 (DMS组 )、依地酸钙钠组 (EDTA组 )、二巯基丙磺酸钠组 (DMPS组 )、青霉胺组 (PCA组 )及二巯基丁二酸组 (DMSA组 )等六个治疗组 ,对各组治疗前后的尿铜等元素、疗效及不良反应进行对比。结果　治疗前后尿排铜量对比GSH组无显著变化 ,其他各组由高到低依次为DMPS组 ( 4 8.68± 2 0 .67) μmol·2 4h-1、PCA组 ( 3 0 .0 4± 10 .5 1) μmol·2 4h-1、DMS组 ( 2 4.3 0± 8.60 ) μmol·2 4h-1、DMSA组 ( 18.2 5± 7.73 ) μmol·2 4h-1、EDTA组 ( 10 .5 8± 4.67) μmol·2 4h-1,均较疗前有显著增高 (P <0 .0 1)。上述解毒药对HLD的锌、铁、钙元素代谢亦有一定影响。治疗后各组的有效率依次为DMPS组 ( 78.9% ) >DMS组 ( 74.5 % ) >PCA组 ( 71.3 % ) >DMSA组 ( 69.1% )>EDTA组 ( 5 3 .7% ) >GSH组 ( 2 8.8% ) ,组间对比差异有非常显著性 ( χ2 =73 .5 ,P <0 .0 1)。各治疗组不良反应发生率依次为 :PCA组 ( 4 4.5 % ) >DMPS组 ( 4 3 .8% ) >DMS组 ( 4 2 .2 % ) >DMSA组 ( 4 1.2 % ) >EDTA组 ( 3 9.8% ) ,与GSH组对比差异有非常显著性 ( χ2 =3 3 .6,P <0 .0 1)。常见的     

Chelation in Metal Intoxication XLIV：Efficacy of α—Mercaptoβ—（5—Substituted,2—Furyl） Acrylic Acids in Mobilizing Intracellularly Bound Cadmium in Rat

The efficacy of α-mercapto-β-(2-furyl)acrylic acid(MFA),α-mercapto-β-(5-Sodiumsulfonate,2-furyl)acrylic acid(MSFA)and α-mercapto-β-(5-acetoxymethyl,2-furyl)acrylic acid (MAFA) to mobilze intracellularly bound cadmium in liver and kidney was investigated in rate preexposed to cadmium,MFA was effective in reducing cadmium levels of hepatic and renal supernatant cytosolic fraction(SCF) while MSFA and MAFA were effective in lowering cadmium levels of renal SCF and hepatic SCF respectively.All the chelating agents also enhanced the excretion of cadmium more in feces than in urine,Hoerver,substitution on the furan ring lowered cadmium mobilizing efficacy of the parent compound,MFA,The treatment with MFA did not affect the status of endogenous zinc and copper while the treatment with MSFA and MAFA enhanced their excretion.MSFA increased hepatic and renal zine and renal copper while MAFA increased their coper levels.     

Preventive and therapeutic role of vitamin E in chronic plumbism

The ability of vitamin E to prevent or treat experimental lead intoxication was investigated in rats. Lead ingestion (10 mg/kg, lead as lead acetate, orally for 6 weeks) significantly inhibited the activity of blood delta-aminolevulinic acid dehydratase (ALAD), reduced the brain dopamine (DA) contents, enhanced the blood zinc protoporphyrin, and enhanced the urinary excretion of delta-aminolevulinic acid (ALA). Lead exposure also elevated brain norepinephrine, homovanillic acid, and 5-hydroxyindole acetic acid (5-HIAA) levels and concentration of lead in blood and tissue. Simultaneous supplementation of vitamin E along with lead significantly reduced the inhibition of blood ALAD activity, brain DA and 5-HIAA levels, and elevation of urinary ALA excretion. Blood and liver lead concentrations were also significantly reduced by simultaneous supplementation with vitamin E. Postlead exposure treatment with vitamin E was ineffective in reducing the lead-induced effects, except that the inhibition of blood ALAD activity was slightly reduced. The present results suggest that vitamin E given simultaneously with lead is effective in reducing the severity of lead intoxication.     

离子络合剂及常见阳离子对博莱霉素作用淋巴细胞SCE的影响

目的观察几种离子和离子络合剂对博莱霉素作用淋巴细胞SCE的影响。方法在含有一定量BLM的人外周血淋巴细胞培养物中注入一定量的几种金属离子或离子络合剂，统计淋巴细胞的姐妹染色单体交换率（sister chromatid exchanges，SCE率）的变化，以观察这些离子对BLM的影响作用。结果终浓度为0．5和1．0mmol／L的Fe^2＋、终浓度为2．0和4．0mmol／L的Mg^2＋在BLM切割DNA上有明显的促进作用（P〈0．05）；终浓度为2．0mmol／L的Fe^2＋则有极其明显的促进作用（P〈0．01）；同为2．5mmol／L的EDTA和枸橼酸钠（SC）则有明显的拮抗作用（P〈0．05）。结论一定量的Fe^2＋和Mg^2＋的存在对于BLM切割DNA的过程是必需的，EDTA和枸橼酸钠的络合作用则从反面印证了该结论。     

灵芝及其与丹参、五味子、柴胡配伍对小鼠实验性肝损伤的影响

目的　探讨灵芝醇提物分别与柴胡、丹参、五味子醇提物配伍后对小鼠实验性肝损伤的保护作用。方法　分别采用四氯化碳 (CCl4 )或D 氨基半乳糖 (D GlaN)诱导的小鼠肝损伤模型 ,给予同一剂量的药物 ,测定血清及肝组织ChE和ALT活性 ,肝组织MDA、ALP、GSH含量 ,VG染色观察肝组织形态学变化。结果　CCl4 所致小鼠血清ALT急剧升高 ,ChE显著下降 ,灵芝及灵芝 +五味子、灵芝 +柴胡组有显著降低和升高作用 ;灵芝各配伍组可显著抑制GSH的升高 ,对MDA的升高只有灵芝 +五味子可显著抑制 ,使其降至正常水平。对D GlaN所致模型组的ChE活性影响不明显 ;灵芝组可使显著升高的ALT活性明显降低 ;对GSH的升高 ,灵芝 +丹参有影响 ,但差异无显著性。灵芝及灵芝各配伍组对升高的MDA有显著降低作用 (P <0 .0 1) ,病理切片观察表明 ,灵芝及灵芝 +五味子组对肝细胞的损伤有较好的修复作用。结论　灵芝对实验性肝损伤有一定的保护作用 ,与五味子配伍作用更明显。这一作用机制可能与抗肝细胞氧化损伤有关     

口服谷胱甘肽在血浆及肝脏分布的实验研究

目的 研究小鼠口服谷胱甘肽后在血浆及肝脏的药物浓度变化。方法 用高效液像色谱仪检测小鼠口服GSH(0．3和3．2mmol／kg)0．125、0．5、1、2、4和8h，血浆及肝脏中的药物浓度。结果 小鼠口服小剂量0．3mmol／kgGSH后，血药浓度变化不大，只有在大剂量3．2mmol／kg时，血药浓度才有明显变化。而肝脏GSH浓度在大、小剂量时均有显著增加。结论 小鼠口服GSH后血浆中的药物浓度不高，但能在肝脏中获得很高的药物浓度。     

Protection Against Hepatic Ischemia—reperfusion Injury in Rats by Oral Pretreatment With Quercetin

To investigate the possible protection provided by oral quercetin pretreatment against hepatic ischemia-reperfusion injury in rats.Methods:The quercetin(0.13 mmol/kg) was orally administratedin 50 min prior to hepatic ischemia-reperfusion injury,Ascorbic acid was also similarly administered.The hepatic content of quercetin was assayed by high performance liquid chromatography (HPLC).Plasma glutamic pyruvic transaminase(GPT),glutamic oxaloacetic transaminase(GOT) activities and malondiadehyde(MDA) concentration were measured as markers of hepatic ischemia-reperfusion injury.Meanwhile,hepatic content of glutathione(GSH),activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px) and xanthine oxidase(XO),total antioxidant capacity (TAOC),contents of reactive oxygen species(ROS) and MDA,DNA fragmentation were also determined.Results:Hepatic content of quercetin after intragastric administration of quercetin was increased significantly.The increases in plasma GPT,GOT activities and MDA concentration after hepatic ischemia-reperfusion injury were reduced significantly by pretreatment with quercetin.Hepatic content of GSH and activities of SOD,GSH-Px and TAOC were restored remarkably while the ROS and MDA contents were significantly diminished by quercetin pretreatment after ischemia-reperfusion injury.However,quercetin pretreatment did not reduce significantly hepatic XO activity and DNA fragmentation.Ascorbic acid pretreatment had also protective effects against hepatic ischemia-reperfusion injury by restoring hepatic content of GSH,TAOC and diminishing ROS and MDA formation and DNA fragmentation.Conclusion.It is indicated that quercetin can protect the liver against ischemia-reperfusion injury after oral pretreatment and the underlying mechanism is associated with improved hepatic antioxidant capacity.     

Porphobilinogen and Delta-Aminolevulinic Acid Excretion in Multiple Sclerosis

The excretion of delta-aminolevulinic acid and porphobilinogen in the urine of 31 patients with multiple sclerosis did not differ significantly from that of 51 hospitalized control patients or eight patients with poliomyelitis. There was no relationship between exacerbations, remissions or duration of the illness, and levels of delta-aminolevulinic acid or of porphobilinogen. These assays therefore appear to be of no value in the differential diagnosis of multiple sclerosis or in following the severity or stage of this illness. Whereas demyelination does occur in acute porphyria where the levels of delta-aminolevulinic acid and porphobilinogen are elevated, the converse is not true; that is, demyelination is not always associated with an increase in the excretion of porphobilinogen or delta-aminolevulinic acid.     

Effect of N,N-Dimethylglycine on Homocysteine Metabolism in Rats Fed Folate-Sufficient and Folate-Deficient Diets

Objective This study aimed to investigate the effects of N,N-dimethylglycine (DMG) on the concentration and metabolism of plasma homocysteine (pHcy) in folate-sufficient and folate-deficient rats. Methods In this study, 0.1％ DMG was supplemented in 20％ casein diets that were either folate-sufficient (20C) or folate-deficient (20CFD). Blood and liver of rats were subjected to assays of Hcy and its metabolites. Hcy and its related metabolite concentrations were determined using a liquid chromatographic system. Results Folate deprivation significantly increased pHcy concentration in rats fed 20C diet (from 14.19 ± 0.39 μmol/L to 28.49 ± 0.50 μmol/L; P < 0.05). When supplemented with DMG, pHcy concentration was significantly decreased (12.23 ± 0.18 μmol/L) in rats fed 20C diet but significantly increased (31.56 ± 0.59 μmol/L) in rats fed 20CFD. The hepatic methionine synthase activity in the 20CFD group was significantly lower than that in the 20C group; enzyme activity was unaffected by DMG supplementation regardless of folate sufficiency. The activity of hepatic cystathionine β-synthase (CBS) in the 20CFD group was decreased but not in the 20C group; DMG supplementation enhanced hepatic CBS activity in both groups, in which the effect was significant in the 20C group but not in the other group. Conclusion DMG supplementation exhibited hypohomocysteinemic effects under folate-sufficient conditions. By contrast, the combination of folate deficiency and DMG supplementation has deleterious effect on pHcy concentration.     

维生素K对去卵巢大鼠肝氧化应激及炎症因子的影响

目的：探讨补充维生素K对去卵巢大鼠肝氧化应激及炎症的影响。方法：以去卵巢SD大鼠作为围绝经期模型,比较维生素K补充与不补充对肝组织丙二醛,超氧化物歧化酶（SOD）,还原型谷胱甘肽（GSH）等氧化应激指标以及肿瘤坏死因子α（TNF-α）和白介素6（IL-6）的影响。将30只6月龄雌性SD大鼠随机分为3组,每组均为10只,即假手术组,去卵巢组以及去卵巢后补充维生素K组（维生素K组）。术后1周开始分组给药,维生素K组将维生素K混于丙三醇中每日灌胃,而似手术组和去卵巢组每日给予丙三醇灌胃。90d后,取肝组织测定丙二醛,SOD,GSH;冰冻切片行苏木素-伊红（HE）与活性氧（ROS）荧光染色;免疫印迹检测TNF-α和IL-6的表达。结果：维生素K组肝组织丙二醛水平较去卵巢组明显降低,但明显高于假手术组（P均〈0．05）。维生素K组肝组织SOD,GSH水平均较去卵巢组明显降低（P〈0．05）,与假手术组比较差异无统计学意义。形态学检测表明维生素K组肝细胞胞质内小空泡数目明显少于去卵巢组,而假手术组则未见空泡;维生素K组肝细胞内活性氧荧光强度明显低于去卵巢组,与假手术组相近。免疫印迹结果表明维生素K组肝内TNF-α与IL-6表达水平均介于去卵巢组和假手术组之间;去卵巢组两种因子水平明显高于假手术组。结论：去卵巢大鼠肝组织处于较高的氧化应激状态,并伴有促炎因子表达增高,这种改变能在一定程度上被维生素K缓解。     

静脉补铁联合还原性谷胱甘肽对维持性血液透析患者氧化应激的影响

目的 观察维持性血液透析(MHD)患者在静脉补铁治疗肾性贫血的过程中,联合应用还原性谷胱甘肽(GSH)对体内氧化应激(OS)的影响.方法 选择MHD患者40例,随机分为静脉补铁组(Fe组)20例,静脉补铁联合GSH组(Fe+GSH组)20例,治疗8周后观察用药前后血红蛋白(Hb)、红细胞比容(Hct)、血清铁蛋白(SF)、转铁蛋白饱和度(TAST)以及血浆中丙二醛(MDA)、过氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-px)等指标的变化.结果 治疗8周后,Fe组和Fe+GSH组Hb,Hct水平均较治疗前明显升高(P<0.01),与Fe组相比,Fe+GSH组Hb、Hct水平改善明显,差异有统计学意义(P<0.05);治疗8周后Fe组和Fe+GSH组SF与TAST水平较治疗前显著增高(P<0.01),Fe组和Fe+GSH组之间比较,差异无统计学意义(P>0.05);治疗8周后,Fe组MDA较治疗前显著升高(P<0.05),SOD、GSH-px显著下降(P<0.05),而Fe+GSH组各项氧化应激指标较治疗前无明显改变(P>0.05),Fe组和Fe+GSH组之间比较,差异有统计学意义(P<0.05).结论 静脉补铁可有效改善MHD患者贫血及缺铁,但也加剧了患者体内的氧化应激状态,联合应用GSH可有效抑制患者体内氧化应激状态.     

Carbon monoxide may enhance bile secretion by increasing glutathione excretion and Mrp2 expression in rats

BackgroundNitric oxide (NO) donors have been reported to induce choleresis via an increased excretion of glutathione. The effects of another gas molecule, carbon monoxide (CO), on bile formation are, however, inconsistent among previous reports. We investigated the sequential changes of bile output and the biliary contents in rats with or without CO supplementation to elucidate the mechanism of CO on bile excretion.MethodsDichloromethane (DCM) was gastrically fed to male Sprague–Dawley rats to yield CO by liver biotransformation. The rats were divided into DCM-treated (n = 7), DCM plus L-NAME-treated (n = 6), and corn oil-treated-(n = 8) groups. Bile samples were collected hourly to examine the flow rate and bile content. Serum levels of nitrite and nitrate 4 hours after DCM supplementation with or without NO synthase (NOS) inhibition were measured by capillary electrophoresis. The expression of hepatic inducible NOS was evaluated by Western blotting 6 hours after DCM administration.ResultsLevels of carboxyhemoglobin rose to around 10% at 4 hours after DCM supplementation and were maintained until the end of the experiments. Bile flow increased after DCM supplementation and was associated with a concomitant increase of biliary glutathione and higher hepatic multidrug resistance-associated protein 2 (Mrp2) expression. Hepatic inducible NOS expression and serum nitrate/nitrite levels were also increased. Treatment with an NOS inhibitor (L-NAME) abolished the CO-induced glutathione excretion and choleresis, but not Mrp2 expression.ConclusionThe present study demonstrated that CO enhanced biliary output in conjunction with NO by increasing the biliary excretion of glutathione. The increment in biliary glutathione was associated with an increased expression of hepatic Mrp2.     

荞麦种子总黄酮对四氯化碳所致急性肝损伤的保护作用

目的研究荞麦种子总黄酮(totalflavonoids of buckhwheat seed,TFBS)对四氯化碳造成的小鼠急性肝损伤的保护作用.方法四氯化碳造成小鼠急性肝损伤模型,测定肝脏指数(liver index,LI):血清谷丙转氨酶(serum glutamicpyruvic transaminase,SGPT)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC),肝组织谷丙转氨酶(liver glutamic pyruvic transaminase,LGPT)、丙二醛(malonaldehyde,MDA)、超氧化物歧化酶(superoxidase dismutase,SOD)以及谷胱甘肽(glutathione,GSH)等指标,采用光镜观察肝脏组织学变化.结果与四氯化碳模型组比较,经TFBS预防性治疗后,SGPT、LGPT、TG、TC和MDA含量均明显降低(P＜0.05,P＜0.01),而GSH含量有所升高,同时SOD活力明显增强(P＜0.05).通过病理学切片观察,TFBS能明显改善肝组织的病理变化.结论TFBS对四氯化碳造成的小鼠急性肝损伤具有保护作用.     

抗氧化剂拮抗甲基汞诱导的脂质过氧化作用研究

目的 探讨抗氧化剂对甲基汞诱导的脂质过氧化的拮抗作用。方法 运用硫代巴比妥酸比色法,检测了谷胱甘肽（ＧＳＨ）、羧乙基锗倍半氧化物（Ｇｅ－１３２）、维生素Ｃ（ＶｉｔＣ）等对甲基汞在体外诱导的大鼠脂质过氧化物（ＬＰＯ）的影响。结果 与阳性对照组相比,２、４、６ｍｍｏｌ／Ｌ ＧＳＨ组大脑、小脑和肝组织匀浆中ＬＰＯ含量均显著下降（Ｐ〈０．０５）;０．５、１．０、１．５、２．０ｇ／Ｌ Ｇｅ－１３２组以及０．     

壳聚糖-乙二胺四乙酸纳米粒的制备及小鼠体内~（89）Sr~（2＋）促排作用研究

目的合成壳聚糖-乙二胺四乙酸（CTS-EDTA）纳米粒,用于小鼠体内89Sr2＋的加速排泄研究。方法通过CTS-EDTA上的游离氨基与多聚磷酸钠（TPP）的静电作用制备CTS-EDTA纳米粒,并利用CTS-EDTA纳米粒两性离子型螯合物的特点,比较不同药物对体内放射性核素的促排效果差异。结果 CTS-EDTA纳米粒通过透射电镜观察显示可得到粒度均一的球形纳米粒子,通过激光粒度分析仪测得平均粒径为10.18nm。通过对小鼠体内放射性锶的促排研究发现,CEC-Nano和CEC有良好的促排效果,单次用药后30min和2h时相点对沉积于股骨中放射性锶的促排效率都明显高于EDTA-Na2（P〈0.05）。多次给药时,CEC-Nano和CEC通过尿、粪排泄放射性锶的作用也优于传统药物EDTA-Na2（P〈0.05）。结论通过该实验方法可制备纳米型放射性核素促排剂,为进一步研制广谱放射性核素污染促排剂提供实验依据。     

A comparative clinical trial evaluating efficacy and safety of fixed dose combination of nimesulide (100 mg) and racemethionine (50 mg) (namsafe) versus reference drug (nimesulide) and other NSAIDs in the treatment of osteoarthritis

Sixty consecutive patients of either sex, above the age of 18 years with symptoms of osteo-arthritis participated in this open, randomised, comparative clinical trial carried out over 3 months. Patients were randomised into 5 groups: Group A (paracetamol 500 mg), group B (ibuprofen 400 mg), group C (nimesulide 100 mg), group D (diclofenac 50 mg), and group E [fixed dose combination of nimesulide (100 mg) and racemethionine (50 mg) (namsafe)]. The efficacy parameters were pain intensity, pain on movement, tenderness and swelling. The liver function tests were carried out to estimate the effect of the drugs on the hepatic profile. The Wilcoxon signed rank test and the Kruskal Wallis (one way ANOVA) test were utilised to evaluate the significance of the change from baseline to the final visit. The treatment with combination of nimesulide and racemethionine gave the best relief from tenderness. With respect to pain intensity and pain movement, combination of nimesulide and racemethionine with nimesulide efficacy was comparable. Theliver function test data at the end of 6 months show that combination of nimesulide and racemethionine treated group showed the least rise in the serum asparatate aminotransferase and alanine aminotransferase levels, whereas in the other treatment groups it was very pronounced. Thereby, combination of nimesulide and racemethionine is found to be better for the long-term treatment of osteo-arthritis in patients. The combination of the two agents, namely nimesulide and racemethionine is expected to augment the safety profile of nimesulide, without influencing the effectiveness of the analgesic agent, i.e., nimesulide.     

Effects of Na2 EDTA and Alpha-chymotrypsin on Aqueous Humor Outflow Conductance in Monkey Eyes

In glaucoma there is partial clogging of the outflow routes for aqueous humor between the anterior chamber and the canal of Schlemm. In monkeys chelating agents perfused from the anterior chamber markedly reduce the outflow resistance, but the effect is short-lasting. In the present study an attempt was made to prolong the effect of Na₂EDTA with alpha-chymotrypsin and the effect of this agent alone was also tested. After 30 min of perfusion with 50 U/ml alpha-chymotrypsin there was a marked rise in outflow conductance, which was well maintained during subsequent perfusion without the enzyme. Two hrs after enzyme perfusion the rise in outflow conductance was 1.25±0.20μl·min^?1·cm H₂O^?1 from a starting level of 0.33±0.08μl·min^?1·cm H₂O^?1. In eyes perfused with alpha-chymotrypsin and 0.5 mmol/l Na₂EDTA in ⁺⁺Na- and ⁺⁺Mg- free perfusate for 30 min the rise in outflow conductance observed 2 hrs later was 1.72±0.20μl·min^?1·cm H₂O^?1. No adverse effects were observed in the eyes during the experiments and the next few weeks. The results indicate that perfusion with alpha-chymotrypsin produces relatively wide routes for aqueous drainage into the canal of Schlemm, which remain patent at least for several hours. In addition the enzyme seems to prolong the effect of Na₂EDTA     

Wilson's disease with hepatic presentation in childhood

Diagnosis of Wilson's disease with hepatic presentation in childhood using clinical and common laboratory parameters is still challenging and is often missed or delayed. The aim of the study was to document the clinical and laboratory parameters of hepatic presentation of Wilson's disease in children. The study was conducted at a tertiary-care hospital in a developing country. Clinical and common laboratory parameters were recorded in 32 Wilson's disease children with hepatic presentation. The diagnosis was based on positive family history, Kayser-Fleischer ring, low serum ceruloplasmin level, elevated basal urinary copper excretion and favorable response to therapy with D-penicillamine. Mean age+/-SD at presentation was 9+/-2.97 years and 21 (65.6%) were boys. Chronic liver disease (21; 65.6%) followed by fulminant hepatic failure 1(6; 18.8%) were the commonest presentation. In the whole group, Kayser-Fleischer ring was found in 21 (65.6%), low serum ceruloplasmin in 16 (50%) and elevated basal urinary copper excretion in all 32 (100%) children. Diagnosis of Wilson's disease was made at presentation on the basis of i) Kayser-Fleischer ring, low serum ceruloplasmin, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 11 (34.4%), ii) Kayser-Fleischer ring, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 10 (31.2%), iii) elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 6 (18.8%) and iv) low ceruloplasmin, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 5 (15.6%) children. Wilson's disease can not be excluded in children presenting with hepatic involvement using the commonly practiced clinical and laboratory parameters. A combination of various clinical and laboratory parameters were used for the diagnosis of Wilson's disease in the studied children with hepatic presentation.