丙烯酰胺中毒大鼠血清和坐骨神经抗氧化能力时效变化

目的探讨丙烯酰胺（ACB）中毒大鼠血清、坐骨神经抗氧化指标的时间效应变化.方法选用雄性Wistar大鼠以40 mg/kg剂量ACB腹腔注射,对照组注射生理盐水,每周3次,连续10周,分别于0、2、4、6、10周取材,测血清、坐骨神经的氧化抗氧化指标.结果与对照组相比,随染毒时间延长,血清谷胱甘肽含量呈进行性降低,第6、10周分别降为对照组的92%和77%.坐骨神经中第2、4、6、10周分别降为92%、82%、67%和66%,差异有统计学意义（P＜0.05或P＜0.01）.丙二醛含量呈进行性增加,在血清中第4、6、10周分别增为对照组的113%、118%和120%;坐骨神经中第4、6、10周分别增为153%、167%和174%,差异有统计学意义（P＜0.05或P＜0.01）.抗活性氧单位水平降低,与对照组的差异有统计学意义（P＜0.05或P＜0.01）.谷胱甘肽过氧化物酶的活力进行性增加,在血清中第2、4、6、10周分别增为122%、130%、160和124%;坐骨神经中第4、6、10周分别增为134%、152%和164%,差异有统计学意义（P＜0.05）.谷胱甘肽还原酶的活力初期增加,后期则降低;坐骨神经中第6、10周分别降为59%和33%,差异有统计学意义（P＜0.01）;超氧化物歧化酶活力初期增加,后期降低,血清中第10周降为对照组的85%,差异有统计学意义（P＜0.05）.坐骨神经和血清中各指标随步态评分的改变与随时间的改变情况相近.血清和坐骨神经中丙二醛含量呈高度相关关系,差异有统计学意义（P＜0.01）;以染毒时间和步态评分为依据的相关系数分别为0.99,0.96.结论ACR中毒大鼠血清、坐骨神经中抗氧化指标改变存在时间-效应关系,两组织中存在相似的变化规律,而坐骨神经中变化较明显.     

甲胺磷对母鸡坐骨神经中神经丝蛋白的影响

目的观察甲胺磷诱导母鸡迟发性神经毒性时坐骨神经中神经丝蛋白的变化。方法皮下注射甲胺磷30mg/kg,连续15d。分别在母鸡呈现迟发性神经毒性症状的第2天、第10天和第23天,采用免疫印记法检测坐骨神经沉淀和上清液中神经丝亚单位高分子量神经丝(NF H)、中分子量神经丝(NF M)和低分子量神经丝(NF L)的含量。结果坐骨神经沉淀中,NF H积分密度(IOD)值在呈现症状第2天为145117±17038,比对照组的78875±22569升高了84%,呈现症状第10天和第23天分别为55917±17333和45038±6662,与对照组比较,分别降低了29%和43%;NF M的IOD值在呈现症状第2天时为31493±4625,与对照组的27925±2660比较,差异无统计学意义;呈现症状第10天和第23天分别为19367±2746和6612±1119,明显低于对照组;NF L的IOD值在呈现症状第2天时为39211±3800,明显高于对照组的28749±9319;第10天和第23天分别为27974±3611和21507±2286,与对照组比较差异无统计学意义。3个时间点上清液中NF H的IOD值分别为4709±1739、12337±3205和16745±931,均明显低于对照组的44083±6895;NF M含量明显降低,呈现症状第2天的IOD值为3196±269,比对照组的17243±3232降低了81%,第10天时仅检测到微量,第23天时的IOD值为5206±1292,比对照组降低了70%;呈现症状第2     

The effects of ivermectin used in combination with other known antiparasitic drugs on adult Onchocerca gutturosa and O. volvulus in vitro

The effects of ivermectin at a concentration of 3.13 x 10(-6) M used in combination with other antiparasitic drugs on the viability of adult Onchocerca in vitro were assessed using MTT colorimetry and worm motility levels. When ivermectin was used against male O. gutturosa over a 7 d period in combination with suramin (5 x 10(-5) M), CGP 6140 (3.13 x 10(-6) M), CGP 20376 (1.95 x 10(-7) M), mefloquine (3.13 x 10(-6) M), levamisole (3.13 x 10(-6) M), mebendazole (5 x 10(-5) M), flubendazole (5 x 10(-5) M) and albendazole (5 x 10(-5) M), there was either no increased effect or only a marginally increased effect on motility levels when compared with the use of ivermectin alone. MTT colorimetry revealed that in most cases there was a cumulative effect of the 2 drugs used in combination but not a synergistic effect. In a trial extended to 26 d it was demonstrated that the combination of ivermectin and suramin did not produce a greater inhibition of motility than ivermectin alone. Using female O. volvulus, the activity of ivermectin, CGP 6140 and the 2 drugs combined was examined. The motility of all 3 groups exposed to drug(s) was suppressed by 24 h compared with controls. MTT colorimetry performed on day 7, using the pre-weighed anterior end of each worm, illustrated that ivermectin alone produced a 43.4% inhibition of formazan formation compared with controls, CGP 6140 alone produced 50.6% inhibition, while the drug combination produced a 72% inhibition, equivalent to the heat-killed control.(ABSTRACT TRUNCATED AT 250 WORDS)     

他可莫司对丙烯酰胺中毒大鼠热休克蛋白70及Bcl-2和Bax蛋白表达的影响

目的 探讨他可莫(tacrolimus,FKS06)对丙烯酰胺(acrylamide,ACR)中毒大鼠行为学和热休克蛋白70(HSP70)及神经元凋亡相关蛋白Bcl-2和Bax表达的影响.方法 40只Wistar雄性大鼠随机分成4组:正常对照组(生理盐水)、模型组(30mg/kgACR)、FK506低剂量组(30mg/kg ACR+0.5mg,kgFK506)和高剂量组(30ms/kg ACR+1.0ms/ksFK506).各组给药5次/周,持续4周,每周进行步态评分;第28天后用蛋白免疫印迹法(Western bloting)方法检测HSP70及Bci-2、Bax蛋白表达水平的变化.结果 与模型组相比,FK506低、高剂量组大鼠步态评分分值分别降低了30.1%和47.7%,差异有统计学意义(P<0.01).与模型组相比,FK506低、高剂量组除脊髓中HSP70表达不明显.大脑和坐骨神经中HSP70表达分别增加了11.6%、33.3%和56.3%、58.5%,差异有统计学意义(p<0.05或P<0.01);与模型组比较,FKS06低剂量组的大脑、脊髓中Bcl-2蛋白表达变化均不明显,坐骨神经中Bcl-2蛋白表达增加了39.1%,差异有统计学意义(P<0.01);FK506高剂量组Bcl-2蛋白表达在大脑、脊髓和坐骨神经中分别升高了16.3%、14.8%和56.0%,差异有统计学意义(P<0.01),与模型组比,FK506低剂量组脊髓中Bax蛋白表达降低46.8%,FK506高剂量组大脑和脊髓中分别降低了16.4%和40.2%,差异均有统计学意义(P<0.01);FKS06低、高剂量组在大脑、脊髓和坐骨神经组织中Bcl-2/Bax比值分别升高了15.9%、33.3%、36.9%和30.1%、49.1%、60.1%,差异均有统计学意义(P<0.01).结论 FK506对丙烯酰胺中毒大鼠神经损伤有保护作用,HSP70、Bcl-2表达上调,Bax表达下调可能是其保护机制之一.     

甲胺磷对鸡坐骨神经中微管和微丝蛋白水平的影响

目的研究甲胺磷诱发迟发性神经病动物的坐骨神经中微管蛋白和微丝中β-肌动蛋白水平随时间变化的趋势。方法母鸡以30mg／kg甲胺磷连续15d经皮下注射染毒，出现迟发性神经病症状后的第2、10和23天，分别取其坐骨神经匀浆，用Western blotting法检测鸡坐骨神经中α-．微管蛋白、β-微管蛋白和β-肌动蛋白的水平。结果鸡坐骨神经上清液中α-微管蛋白水平随时间延长逐渐下降，出现迟发性神经病症状后的第2、10和23天分别降低了6％、15％和25％，沉淀中变化不明显；β-微管蛋白水平在各时间点均降低：在第2、10和23天，沉淀中的水平分别下降了27％、6％和19％，上清液则分别降低了1％、21％和22％；沉淀中β-肌动蛋白水平升高：第2、10和23天分别升高了24％、48％和17％；上清液中β-肌动蛋白水平的变化不明显。结论甲胺磷可导致母鸡坐骨神经α-微管蛋白、β-微管蛋白和β-肌动蛋白改变，可能是甲胺磷诱发动物迟发性神经病的机制之一。     

Susceptibility of Plasmodium falciparum to different doses of quinine in vivo and to quinine and quinidine in vitro in relation to chloroquine in Liberia

Chloroquine-resistant Plasmodium falciparum has been spreading rapidly after its emergence in 1988 in Yekepa. The in vivo and in vitro susceptibilities to quinine and quinidine, compared to chloroquine, were studied by investigating the number of treatment days required for radical cure and estimating the quinine concentrations concomitantly. The minimal inhibitory concentrations (MIC) for schizont maturation in all successful in vitro tests were 5.12 x 10(-6) mol/l for quinine and 1.28 x 10(-6) mol/l for quinidine, indicating that all 50 isolates were sensitive to the two drugs. The IC50 and IC90 values were 0.22 and 0.78 x 10(-6) mol/l for quinine and 0.07 and 0.26 x 10(-6) mol/l for quinidine, respectively. In vitro inhibition of parasites by 1.6 x 10(-6) mol/l of chloroquine was obtained in 31 out of 47 isolates, 16 (34%) being resistant. The IC50, IC90 and geometrical mean MIC for quinine were all about two times higher for the chloroquine-resistant than for the chloroquine-sensitive isolates (P = 0.006). P. falciparum infected children (n = 64) were randomly allocated to four groups and treated with quinine (10 mg/kg body weight twice daily) for 1 day (3 doses), 2, 4 and 7 days, respectively. All cleared their parasitaemias by day 4 but 5 out of 15 of those treated with only three doses showed a recurrence of parasitaemia between days 7 and 14; these were considered to be recrudescences. In the other groups, recurrent parasitaemias only occurred between days 17 and 28 and were considered to be reinfections.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intestinal absorption of pyridoxal 5'-phosphate at physiological levels in rats

The intestinal absorption of pyridoxal 5'-phosphate (PLP) at physiological levels (10(-7) -10(-6) M) was studied in comparison with that of pyridoxal (PL) in rat, using in vitro everted sac and an intestinal preparation that permitted continuous in situ collection of mesenteric venous blood. After PLP administration (10(-6) -10(-3) M) in situ, larger amounts of PLP were found in the mesenteric venous plasma than after PL administration at the same dose. The amount of PLP found in the mesenteric venous plasma was dependent on its dose at lower concentrations up to 10(-4) M but became independent at higher concentrations. After PL administration at various doses, the amount of PL found in the mesenteric venous blood increased linearly with the dose. When various concentrations of PLP were added to the mucosal side, under the in vitro condition with protection from alkaline phosphate hydrolysis, PLP was detected in the serosal side and the extent of PLP transport was dependent on the initial concentration of PLP in the mucosal side. When various concentrations of PL were added to the mucosal side, the extent of PL transport was independent of the initial concentration of PL in the mucosal side. In rat pretreated with actinomycin D, PLP transport in vitro was inhibited but not that of PL. N2-induced anoxia and pyridoxamine 5'-phosphate and anion transport inhibitor (4,4'-diisothiocyanostilben-2,2'-disulfonic acid disodium salt) showed no effect on PLP transport. These results suggest that PLP can be absorbed in the phosphorylated form and imply the presence of a saturable process for direct absorption of PLP itself and a diffusive process for PL absorption. In addition, the result of the in vivo neonatal experiment suggests that the neonatal intestine also can transport PLP in phosphorylated form.     

New quinoxalinecarbonitrile 1,4-di-N-oxide derivatives as hypoxic-cytotoxic agents

We report the synthesis and biological in vitro activities of 16 new 2-quinoxalinecarbonitrile 1,4-di-N-oxides. These compounds present new basic lateral chains (piperazines and anilines) in the 3 position as well as different substituents in the 6 and/or 7 positions of the quinoxaline ring. Among piperazine derivatives, 4b (a 7-chloro-3-(4-methylpiperazin-1-yl) derivative) was the most potent (P = 0.5 x10(-6) M). In general, aniline derivatives were more potent and selective than the former, compound 12b (with a 4-(methylphenyl)amino moiety in the 3 position and a chlorine atom in the 7 position) being the best one (P = 3 x 10(-6) 16).     

Addition of steroids to embryo-uterine monolayer co-culture enhances embryo survival and implantation in vitro

Co-culture with a mixed cell monolayer established from trypsinized uterine tissue increased the numbers of embryos developing in a minimum essential medium beyond the hatching blastocyst stage in the 5-day period of culture to 56.0% (343/613) compared with 30.2% (93/308) for embryos cultured in medium alone. The inclusion of progesterone (3.2 x 10(-6), 3.2 x 10(-5), or 3.2 x 10(-4) M) or oestradiol (3.7 x 10(-5) M) to the co-cultures increased the mean percentage of embryos developing to the advanced stages to 72.7-78.4%. The addition of progesterone (3.2 x 10(-6) M) together with oestradiol (3.7 x 10(-5) M) resulted in additional improvement to a mean of 86.5% (787/910, P less than 0.001) but the combination was without significant effect on embryos cultured in media alone. Blastocyst viability was not impaired by co-culture as assessed in embryo survival following surgical transfer to pseudopregnant recipients. This study confirms the feasibility of establishing co-culture systems to facilitate investigation of pre-implantation events in vitro and highlights a role of steroid hormones in enhancing the capacity of uterine cells to support pre-implantation-stage embryos.     

Effect of cadmium on T4 outer ring monodeiodination by rat liver

The effect of cadmium on thyroxine (T4) outer ring monodeiodination was studied in vivo and in vitro in the rat liver. One microgram of T4 was incubated with rat liver homogenates in 50 mM Tris--HCl buffer, pH 7.4, with or without 0.5, 5, and 50 mM dithiothreitol (DTT) for 60 min in the presence of 10(-8) to 10(-3) M CdCl2, and the amount of 3,5,3'-triiodothyronine (T3) produced was determined by a specific radioimmunoassay. Subcutaneous injection of CdCl2, 1 mg/kg BW/day, 5 days a week for 10 weeks, to the rats resulted in a significant reduction in serum T3 concentration (by 37%) and hepatic T3 production from T4 (by 78 to 92%). In vitro addition of 1 microM to 1 mM CdCl2 to liver homogenates caused a concentration-dependent reduction in T3 generation. Without DTT a 50% reduction in the T4 to T3 converting activity was caused by 4 X 10(-6) M CdCl2. DTT (0.5 to 50 mM) partially restored T3 generation roughly in a concentration-dependent manner. These results indicate that cadmium has some effects on the metabolism of thyroid hormone.     

Effect of benzene and its metabolites on natural killer activity of mouse spleen cells in vitro

The effects of benzene and its metabolites, phenol and hydroquinone, on natural killer (NK) activity in mouse spleen cells in vitro were studied. NK activity was evaluated by the specific release percentage of 51Cr from labeled YAC-1 cells after YAC-1 cells (target cells) were incubated with spleen cells (effector cells) of mice at ratios of effector cells to target cells (E/T) of 100/1, 50/1, and 25/1. Benzene was shown to inhibit NK activity at concentrations of 1 x 10(-5) M-5 x 10(-5) M, phenol at concentrations of 1 x 10(-7)-5 x 10(-5) M and hydroquinone at concentrations of 1 x 10(-6) M-1 x 10(5) M. Phenol and hydroquinone depressed NK activity in a dose-dependent manner. This study demonstrated that NK cell function of mouse spleen was depressed by exposure to benzene and its metabolites in vitro. Hydroquinone and phenol have very potent toxicity for suppression of immunosurveillance.     

Synthesis, structure and anticancer activity of novel 2,4-diamino-1,3,5-triazine derivatives

A series of 2-(4,6-diamino-1,3,5-triazin-2-yl)-2-{[4-(dimethylamino)-phenyl]imino}acetonitriles 19-27 have been synthesized by the reaction of 2-(4-amino-6-alkylamino-1,3,5-triazin-2-yl)acetonitriles 10-15 with p-nitrosodimethylaniline. Unexpectedly, a similar reaction of acetonitriles 10, 14, 15, 17 and 18 with nitrosobenzene led to the formation of 4,6-diamino-N-phenyl-1,3,5-triazine-2-carboxamides 28-32. The in vitro antitumor activity of the compounds obtained has been tested and 2-[4-Amino-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-yl]-2{[4-(dimethylamino)phenyl]imino}acetonitrile (19) having remarkable activity against melanoma MALME-3 M cell line (GI(50)=3.3 x 10(-8) M, TGI=1.1 x 10(-6) M) is a leading candidate for further development.     

2,5-己二酮对坐骨神经及运动神经元瘤细胞VSC4.1神经生长因子水平的影响

目的 研究2,5-己二酮(2,5-hexanedione,2,5-HD)对大鼠坐骨神经和运动神经元神经生长因子(nerve growth factor,NGF)水平的影响.方法 应用随机数字表法将50只Wistar大鼠分为400 mg·kg~(-1)·d~(-1),5-HD染毒0、7、14、21-,28 d组,每组10只,采用免疫组织化学显色和荧光定量PCR检测不同时间坐骨神经横断面NGF水平和坐骨神经NGF mRNA水平.选用0、2.5、5.0、10.0、20.0 mmol/L 2,5-HD染毒神经元瘤细胞VSCA.1,应用免疫荧光法观察NGF水平的改变;并选用10.0 mmol/L2,5-HD作染毒剂量,观察0、1、3、6、12、24、48 h NGF水平的变化.结果 随染毒时间延长,坐骨神经NGF呈先增高后降低的趋势;坐骨神经NGF mRNA水平在染毒14 d(2~(-△△Ct)=3.46)、21 d(2~(-△△Ct)=5.28)和28 d(2~(-△△Ct)=3.10)高于染毒0d(2~(-△△Ct)=1)和7 d(2~(-△△Ct)=0.78),差异有统计学意义.各染毒剂量组VSCA.1细胞NGF水平差异有统计学意义(F=188.88,P<0.01);5.0、10.0、20.0 mmol/L组NGF平均荧光强度值(分别为43.24±7.52、43.48±10.86、63.13±10.68)高于0 mmol/L组(16.32±4.20)(q值分别为19.92、19.72、32.78,P值均<0.01)和2.5 mmol/L组(19.78±2.66)(q值分别为17.50、17.42、30.63,P值均<0.01);20.0 mmol/L组高于5.0、10.0 mmol/L组(q值分别为13.04、11.71,P值均<0.01).10.0 mmol/L 2,5-HD染毒不同时间VSCA.1细胞NGF水平差异有统计学意义(F=75.69,P<0.01);染毒6、12、24、48 h NGF平均荧光强度值(分别为18.66±2.89、23.14±6.08、27.66±6.11、17.25±3.05)高于染毒0 h(10.18±1.81)(q值分别为9.64、15.74、21.76、8.50,P值均<0.01)、染毒1 h(9.31±1.28)(q值分别为10.28、16.17、21.95、9.20,P值均<0.01)和染毒3 h(10.44±2.13)(q值分别为9.25、15.24、21.17、8.10,P值均<0.01);染毒12、24 h NGF平均荧光强度值高于染毒6 h(q值分别为5.24、10.77,P值均<0.01)和染毒48 h(q值分别为7.31、13.26,P值均<0.01).结论一定时间内,2,5-HD可导致大鼠坐骨神经和运动神经元NGF的水平升高,有剂量(时间)依赖关系.     

The changing pattern of Plasmodium falciparum susceptibility to chloroquine but not to mefloquine in a mesoendemic area of Somalia

The response of Plasmodium falciparum to chloroquine and mefloquine was investigated in a mesoendemic area of Somalia from 1986 to 1989. Serial in vivo field tests for chloroquine sensitivity were performed and the sensitivity in vitro to chloroquine and mefloquine was evaluated using the standard WHO in vitro microtest. Chloroquine treatment in vivo (25 mg base/kg body weight) resulted in parasite clearance in all patients within 7 d (S/RI) in 1986, while 17%, 19% and 30% RII/RIII responses were found in 1987, 1988 and 1989 respectively. There was consistent increase of parasite clearance time of the S/RI cases in all years. The sensitivity study in vitro in 1986 showed a low degree of chloroquine resistance in 3 of 29 isolates tested and a mean 50% effective dose (EC50) and EC99 of 0.34 x 10(-6) M and 1.99 x 10(-6) M, respectively. In contrast, in 1989, 12 of the 19 isolates tested were resistant to chloroquine. The mean EC50 and EC99 values had increased to 0.78 x 10(-6) M and 7.50 x 10(-6) M respectively. The data in vivo and in vitro indicate a rapid increase of chloroquine resistance both in frequency and degree. All isolates tested in 1986 and 1989 were fully inhibited by mefloquine at 3.2 x 10(-6) M, suggesting full sensitivity. Thus, increased resistance of P. falciparum to chloroquine did not significantly influence the sensitivity pattern of mefloquine.     

Synthesis and antitumour activity of 4-hydroxy-2-pyridone derivatives

4-hydroxy-2-pyridone derivatives 2 were prepared by reaction of 3-amino-3-dialkylaminopropenoates with bis(2,4, 6-trichlorophenyl)malonate. These compounds were further reacted with a set of aldehydes to give bis(pyridyl)methanes 3 and 4. The newly synthesized compounds 2, 3 and 4 were evaluated in vitro as antitumour agents against 60 human tumour cell lines. Some derivatives exhibit tumour growth inhibition activity. In particular, derivative 4g, the most active of the series, possesses significant activity on all cell lines at concentrations ranging from 1 x 10(-6) to 1 x 10(-5) M.     

丙烯酰胺中毒大鼠坐骨神经、小脑和血清中β-葡萄糖醛酸酶活性的测定

大鼠经每日腹腔内注射50mg/kg的丙烯酰胺共10次后,出现双后肢瘫痪等亚急性中毒症状。于自染毒起第5、12、21、36和50天分别对大鼠坐骨神经、小脑和血清中β-葡萄糖醛酸酶(β-G)活性进行测定,发现在第36天(停止染毒后24天)中毒症状明显好转时,坐骨神经中β-G活性显著升高,为对照组的167.15％(P<0.01),第50天时仍持续在高水平,为对照组164％(P<0.01)。小脑中β-G活性仅轻度升高,与对照组比较并无显著性差异。血清中β-G活性未见明显改变。β-G活性测定方法简易、稳定、是观察受损神经修复的灵敏生化指标。     

Inhibition of the outgrowth and elongation of neurites from pheochromocytoma cells by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and preventive effects of dimethylsulfoniopropionate in the presence of nerve growth factor

The combined effects of dimethylsulfoniopropionate (DMSP) (10(-3), 10(-4) and 10(-5) M) with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (5 ng/mL) and the nerve growth factor (NGF) (5 ng/mL) on the outgrowth and elongation of neurites from pheochromocytoma (PC12) cells were examined on RPMI medium containing fetal bovine serum and horse serum with penicillin and streptomycin in collagen-coated dishes for 5 d. The growth was higher in increasing order of the DMSP (10(-3) M), MPTP and NGF, the DMSP (10(-5) M), MPTP and NGF, the MPTP and NGF group and the control group up to 3 d, but not in the NGF and the DMSP (10(-4) M), MPTP and NGF groups. The growth in all the experimental groups showed plateaus from days 4 to 5. The appearance of neurites from the cells in all the groups showed maxima on the 3rd day. The administration of NGF significantly stimulated the outgrowth of neurites from the cells, while the supplementation of MPTP noticeably inhibited the appearance of neurites even in the presence of NGF up to 5 d. However, the addition of DMSP (10(-3 )and 10(-4) M) to the latter group completely prevented the inhibition of the MPTP. These facts were significantly supported by the photographs of neurite-bearing cells on the 3rd day and also by the photometric analyses examining the reaction of MPTP to DMSP, NGF or Collagen IV.     

Synthesis and aldose reductase inhibitory activity of a new series of 5-[[2-(ω-carboxyalkoxy)aryl]methylene]-4-oxo-2-thioxothiazolidine derivatives

Anew series of 5-[[2-(ω-carboxyalkoxy)aryl]methylene]-4-oxo-2-thioxothiazolidine derivatives was synthesized and evaluated for their potency as aldose reductase inhibitors (ARIs). Their activities were examined in terms of their inhibitory effect on rat lens aldose reductase in vitro and in terms of the preventive effect on sorbitol accumulation in the sciatic nerve of streptozotocin (STZ)-induced diabetic rats in vivo. Of these compounds, some of the naphthylmethylene thiazolidine derivatives were comparable to Zenarestat in the inhibitory potency in vitro and in vivo. In particular, compound 30 was 1.5 times more potent than Zenarestat in the in vivo activity, and had an adequate potency for clinical development.     

Intraneural edema following exposure to vibration

Peripheral neuropathy represents a well-known complication from long-term exposure to vibration. In the present study an experimental model is presented with the purpose of analyzing the formation of intraneural edema following vibration exposure. Vibration (82 Hz, peak-to-peak amplitude 0.21 mm) was induced in the hind limb of rats by the use of vibrating electric motors during 4 h/d for 5 d. Tracer techniques (with albumin Evans blue and horseradish peroxidase) were used to study the permeability of intraneural microvessels after the vibration exposure on day 5. It was found that the vibration trauma in this model induced epineurial edema in the sciatic nerve. It is hypothesized that the formation of intraneural edema may be an important pathophysiological factor in the occurrence of vibration-induced neuropathy.     

Novel synthetic approach to N-aryl-4-(3-pyridyl)thiazol-2-amine and analogues using HMCM-41 as catalyst, and their biological evaluation as human platelet aggregation inhibitors

A novel synthetic approach to N-aryl-4-(3-pyridyl)thiazol-2-amine and analogues using HMCM-41, a mesoporous aluminosilicate catalyst and their in vitro ADP-induced platelet aggregation inhibitory activity on human blood platelets is described. Among the test compounds N-(2'-flourophenyl)-4-(3-pyridyl)thiazol-2-amine (9e) was found to be the most potent, IC(50)=4.84x10(-7)M.