Effect of phosphate transporter and methylation inhibitor drugs on the disposition of arsenate and arsenite in rats.

Arsenate (AsV) is biotransformed into the more toxic arsenite (AsIII) and monomethylarsonous acid (MMAsIII), but it is unknown how to decrease production of these harmful metabolites. We investigated the effects of foscarnet and fosfomycin, drugs interacting with the phosphate transporter, on biotransformation of AsV, an analog of inorganic phosphate. The effects of entacapone, an inhibitor of catechol-O-methyl transferase (COMT), and nitrous oxide, an inactivator of methylcobalamin, were also tested on the formation of MMAsIII from AsIII in order to clarify the role of COMT and methylcobalamin in biomethylation of AsIII. Arsenic in bile and urine of control and treated rats receiving AsV or AsIII was speciated by HPLC-HG-AFS. In AsV-injected rats, foscarnet, but not fosfomycin, increased the urinary excretion of AsV and decreased the biliary and urinary excretion of AsIII as well as biliary excretion of MMAsIII. In AsIII-injected rats, however, foscarnet failed to influence the excretion of AsIII and its metabolites, suggesting that this drug inhibits the hepatic uptake and renal reabsorption of AsV, thereby decreasing formation of AsIII and MMAsIII from AsV. Entacapone or nitrous oxide pretreatment slightly or not at all influenced the biliary excretion of MMAsIII and urinary excretion of dimethylarsinic acid (DMAsV) in AsIII-injected rats. In contrast, periodate-oxidized adenosine, an inhibitor of S-adenosylmethionine-dependent methyltransferases, nearly abolished appearance of methylated arsenic metabolites in bile and urine. Thus, foscarnet facilitates urinary clearance of AsV and decreases formation of toxic AsIII and MMAsIII, indicating that this drug may be used to promote elimination and counter toxification of AsV. Because entacapone and nitrous oxide influenced the excretion of MMAsIII and DMAsV negligibly, neither COMT nor methylcobalamin appears to be involved in arsenic methylation in rats.     

Clinical features of circadian rhythm sleep disorders in outpatients

The clinical data of 86 cases of primary circadian rhythm sleep disorder (primary CRSD) were retrospectively examined and compared to 40 cases of secondary circadian rhythm sleep disorder (secondary CRSD), who had presented with some kind of psychiatric or medical disorder, and had exhibited sleep-wake rhythm disorders that were judged to be secondary CRSD based on sleep logs. The comparison of cases found that: (i) the mean age at first presentation to the clinic was significantly younger for primary CRSD compared to secondary CRSD; (ii) more secondary CRSD cases were unemployed than were Primary CRSD cases; (iii) more cases in the secondary CRSD group had a clear trigger for sleep-wake rhythm disorder onset than cases in the primary CRSD group; and (iv) the types of sleep-wake rhythm disorders in the primary CRSD group consisted of delayed sleep phase syndrome (DSPS), 72 (83.7%), non-24 pattern, 11 (12.8%), and irregular, 3 (3.5%). In the secondary CRSD group there were 25 (62.5%) cases of DSPS pattern, 1 (2.5%) of non-24 pattern and 14 (35.0%) with irregular pattern. The 56 (65.1%) cases with primary CRSD showed good response to vitamin B12 and bright light therapy; however, 28 (70.0%) cases with secondary CRSD did not respond to such therapies.     

复方丹参滴丸联合甲钴胺治疗糖尿病周围神经病变44例

目的:观察复方丹参滴丸联合甲钴胺治疗糖尿病周围神经病变的临床疗效。方法:将88例糖尿病周围神经病变患者随机分为观察组与对照组各44例,对照组采用甲钴胺口服治疗,观察组选用复方丹参滴丸联合甲钴胺口服治疗,连续治疗4周后比较两组疗效。结果:观察者血糖、尿素氮、肌酐、血压水平与治疗前比较,差异无统计意义(P0.05);24 h尿蛋白定量较治疗前显著降低(P0.01),且与对照组治疗后比较,差异有统计学意义(P0.01);对照组治疗前后胫神经和正中神经传导速度比较,只有正中神经的感觉神经传导速度明显加快(P0.05),其余各项均无差异。观察者治疗后胫神经和正中神经的运动神经传导速度和感觉神经传导速度均明显加快(P0.01),与对照组治疗后比较,除正中神经感觉神经传导速度无差异外,其他神经传导速度差异均有统计学意义(P0.01);治疗组有效率为93.18%,优于对照组的81.82%。结论:复方丹参滴丸联合甲钴胺治疗糖尿病周围神经病变临床疗效显著,安全可靠。     

甲基维生素B_（12）、维生素B_（12）降低甲基汞含量及免疫与行为毒性作用的研究

研究发现２．０～３．０ｍｇ／ｋｇ甲基维生素Ｂ_（１２）、维生素Ｂ_（１２）均可使孕鼠脑、肝、肾中甲基汞含量明显低于甲基汞组，而对胎仔脑及胎盘中甲基汞含量有明显减少。甲基维生素Ｂ_（１２）、维生素Ｂ_（１２）并可增强机体特异性细胞免疫功能与机体非特异性免疫功能，可改善动物多种行为不良作用。     

甲钴胺体外诱导大鼠骨髓间充质干细胞向神经元样细胞分化

背景：目前骨髓间充质干细胞移植到脊髓损伤动物体内后对脊髓损伤的恢复效果非常有限。甲钴胺是治疗神经系统疾病及损伤的常见药物,其对骨髓间充质干细胞的影响尚不清楚。目的：探讨甲钴胺体外定向诱导骨髓间充质干细胞向神经元样细胞分化的可行性,观察分化后的细胞增殖和生长情况。方法：取大鼠胫腓骨骨髓,采用密度梯度离心贴壁细胞培养法分离、培养骨髓间充质干细胞,取第四五代骨髓间充质干细胞,分别以25,50,100mg/L的甲钴胺进行诱导分化24,48和72h。倒置相差显微镜下连续观察细胞形态学变化,MTT法检测细胞活性,RT-PCR和Western blot法检测特异性标志物Nestin和NSE的表达。结果与结论：甲钴胺诱导骨髓间充质干细胞后大部分细胞变成神经元样细胞。与对照组比较,甲钴胺诱导后细胞活性无明显变化。不同剂量甲钴胺诱导48h后,Nestin和NSE在mRNA和蛋白水平表达均上调,其中100mg/L组表达上调最明显;100mg/L甲钴胺诱导24,48和72h后,Nestin和NSE在mRNA和蛋白水平表达均上调,其中72h表达上调最明显。说明甲钴胺可定向诱导骨髓间充质干细胞向神经元样细胞分化,100mg/L为甲钴胺的较佳诱导浓度。     

维生素B12治疗周围神经病变的临床疗效比较

目的 比较目前临床应用相对较多的两种维生素B12制剂对周围神经病变临床症状的疗效.方法 选取天津市第一医院临床收纳的满足试验条件的神经卡压性周围神经病变患者,随机分为甲钴胺组(41例),腺苷钴胺组(39例)和针灸组(41例),甲钴胺组患者静脉滴注弥可保,每次0.5 mg,1次/d;腺苷钴胺组患者肌肉注射腺苷钴胺,每次0.5 mg,1次/d;针灸组选用针灸理疗、按摩等常规治疗.3组患者均治疗两周.观测治疗后患者的主观症状、各项体征,并严密观察、记录试验期间发生的不良反应事件.结果 3组治疗患者均未见不良反应,甲钴胺组在主观症状、客观体征方面改善均优于腺苷钴胺组及针灸组.结论 甲钴胺作为最新一代的维生素B12临床应用疗效、安全性方面均优于以往维生素B12,且西医治疗周围神经病变较单纯针灸治疗有明显疗效优势.     

Characterization of the Cobalamins Attached to Transcobalamin I and Transcobalamin II in Human Plasma

Insolubilized antibody to transcobalamin I was used to separate transcobalamin I and transcobalamin II. By bioautography of the extracted cobalamins it was shown that transcobalamin II bound more deoxyadenosylcobalamin than did transcobalamin I, and that methylcobalamin accounts for most of the cobalamins attached to transcobalamin I. This finding may indicate that transcobalamin I has a function in the metabolism of methylcobalamin in man.     

硫酸锌联合甲钴胺治疗糖尿病周围神经病变的临床观察

目的探讨硫酸锌和甲钴胺单独应用及二者联合应用治疗糖尿病周围神经病变(DPN)的临床效果。方法选取DPN患者105例,随机分为硫酸锌组、甲钴胺组合联合组,每组35例,3组患者均给予控制血糖、血压等糖尿病综合治疗。分别应用硫酸锌片、甲钴胺片及硫酸锌片联合甲钴胺片治疗DPN,观察患者临床症状及体征,测定患者治疗1月后正中神经和腓总神经的运动传导速度(MNCV)和感觉传导速度(SNCV)。结果治疗后,联合组正中神经和腓总神经的MNCV均显著高于硫酸锌组和甲钴胺组(P0.05);联合组正中神经SNCV显著高于硫酸锌组和甲钴胺组(p0.05),联合组腓总神经的SNCV与硫酸锌组和甲钴胺组比较差异无统计学意义(P=0.259)。联合组临床总有效率显著高于其他2组(P=0.002)。结论硫酸锌联合甲钴胺片治疗DPN对正中神经和腓总神经MNCV及正中神经的SNCV改善程度要优于单独应用硫酸锌和甲钴胺片。