吡喹酮、尼立达唑和呋喃丙胺治疗埃及血吸虫病217例

在毛里塔尼亚,采用随机方法,设四组:分别用吡喹酮、尼立达唑(又名安必拉)、呋喃丙胺和安慰剂(食糖淀粉片)治疗埃及血吸虫病217例。结果表明吡喹酮、尼立达唑和呋喃丙胺均有疗效,其中以吡喹酮和尼立达唑效果为佳,两者疗效相似。但吡喹酮疗程短、服药方法简单,副作用小,呋喃丙胺疗效较差。吡喹酮是治疗埃及血吸虫病较为理想的一种有效药物。     

高压液相色谱法检测脑脊液中吡喹酮浓度

本文用高压液相色谱法检测CSF(脑脊液)中吡喹酮含量,测得脑囊虫病患者CSF中吡喹酮浓度为血浓度的17-22.5％,与正常人相似。慢性脑膜炎患者CSF中吡喹酮浓度仅为血浓度的4.6％,其血脑屏障透过率明显低于囊虫病患者。本文各治疗组CSF中吡喹酮浓度均可达体外杀灭血吸虫和囊虫的最低有效浓度。     

吡喹酮合并呋喃丙胺治疗动物血吸虫病的研究

动物实验与临床研究证明,吡喹酮对日本血吸虫的杀虫效果显著。鉴于小剂量吡喹酮有使血吸虫迅速挛缩和肝移的作用,故设想吡喹酮合并呋喃丙胺有可能获得较高的疗效。本文报道吡喹酮对感染小白鼠与兔体内血吸虫的肝移情况、合并呋喃丙胺的疗效以及合并用药的毒性。     

吡喹酮抗日本血吸虫病疗效中的非特异性免疫作用

据国内外报道,新药吡喹酮(Praziquatel)对三种血吸虫病都有较好疗效。本实验采用吡喹酮、吡喹酮加己烯雌酚、吡喹酮加氯丙嗪引起非特异性免疫机能改变以观察其对疗效的影响。由于植物神经系统与某些非特异性免疫功能可能有关,因而也做了这方面的观察,藉以较全面地探讨非特异性免疫因素对吡喹酮治疗血吸虫病疗效的影响。     

甘露醇与吡喹酮和地塞米松联合治疗脑囊虫病34例

甘露醇与吡喹酮和地塞米松联合治疗脑囊虫病３４例（河南省郑州市１５３医院４５００６５）胡永兴，彭淑芳为防止因单纯服用吡喹酮后导致颅内高压和病情加重，我们对３４例不同类型的脑囊虫病分别采用甘露醇加吡喹酮（二联法），甘露醇加地塞米松加吡喹酮（三联法）治疗，...     

吡喹酮治疗脑囊虫病

吡喹酮(Praziquantelum)(Embay8840),为一新型广谱抗寄生虫药。动物实验证明,对日本血吸虫病以及绦虫病、华支睾吸虫病、肺吸虫病等均有效,临床试用有同样的效果。1977年以来,国内外用吡喹酮。治疗血吸虫病取得了良好效果。近十年来,用该药治疗脑囊尾蚴病也获满意疗效。目前国内经吡喹酮治疗的脑囊虫病人超过1000例,仅有极少数病例在治疗过程中死亡。现就用吡喹酮治疗脑囊虫病的用法、用量、疗效、不良反应的防治等临床用药问题作一简要综述。     

吡喹酮对神经肌肉接头传递的作用

吡喹酮可使电刺激腓总神经所引起的胫前肌收缩反应明显加强。如给腓总神经施加超强刺激,静脉注射筒箭毒碱可减弱肌肉收缩反应,吡喹酮却能加强筒箭毒碱的抑制作用,使神经肌肉传递迅即完全阻断。采用微电极细胞内记录技术研究吡喹酮对离体大鼠膈神经隔肌的作用,发现吡喹酮不明显影响膈肌细胞的静息膜电位。低浓度吡喹酮(2×10~(-4)M)可使微终板电位(mepp)频率明显增加。高浓度吡喹酮8×10~(-4)M则使mepp振幅逐渐变小和消失。吡喹酮在使神经肌肉传递阻滞不断加深的同时,尚能使终板电位的振幅变小,终致完全消失。     

吡喹酮与丙硫咪唑治疗华支睾吸虫病疗效比较

作者应用吡喹酮和丙硫咪唑治疗华支睾吸虫病174例,并对其疗效进行比较。吡喹酮总剂量为150mg/kg,2天疗程。丙硫咪唑分三组总剂量为70mg/kg,100mg/kg,140mg/kg,7天疗程,其治愈率分别97.1％,63.2％,78.5％,93.1％。丙硫咪唑最佳有效量尚须进一步探讨。实践中得知,吡喹酮为治疗华支睾吸虫病首选药物,丙硫咪唑更适用于治疗华支睾吸虫病合并肠道线虫感染者。     

吡喹酮对大鼠单胺介质的影响

吡喹酮是一种新型广谱抗寄生虫药。本文报道用高效液相色谱-电化学检测器联用的方法,测定单胺类神经介质及其代谢物的含量,研究吡喹酮对大鼠单胺类介质的影响。结果表明:吡喹酮(250 mg/kg使脑DA的酸性代谢产物DOPAC,HVA和5-HT的代谢物5-HIAA的含量明显升高,而对DA和NA含量无明显影响。DA酸性代谢物和5-HIAA升高表明吡喹酮能增加DA和5-HT的转换率。     

吡喹酮对神经肌肉接头传递的作用

吡喹酮可使电刺激腓总神经所引起的胫前肌收缩反应明显加强。如给腓总神经施加超强刺激,静脉注射筒箭毒碱可减弱肌肉收缩反应,吡喹酮却能加强筒箭毒碱的抑制作用,使神经肌肉传递迅即完全阻断。采用微电极细胞内记录技术研究吡喹酮对离体大鼠膈神经隔肌的作用,发现吡喹酮不明显影响膈肌细胞的静息膜电位。低浓度吡喹酮(2×10^-4M)可使微终板电位(mepp)频率明显增加。高浓度吡喹酮8×10^-4M则使mepp振幅逐渐变小和消失。吡喹酮在使神经肌肉传递阻滞不断加深的同时,尚能使终板电位的振幅变小,终致完全消失。     

吡喹酮对大鼠体内不同发育时期华支睾吸虫的实验治疗

近年来国内外应用吡喹酮治疗华支睾吸虫病取得了显著疗效。为进一步探讨该药对体内不同发育时期华支睾吸虫的作用及其作用机理,本文进行了实验研究。实验动物为体重200～330g的♀性大鼠。随机分为对照组和治疗组,每鼠经口接种30个华支睾吸虫囊蚴。所用吡喹酮系南京制药厂供给,每片含吡喹酮200mg。治疗时将药加     

Anticestodal Efficacy of Lasia spinosa. Extract Against Experimental Hymenolepis diminuta. Infections in Rats

Abstract

The use of Lasia spinosa. (L.) Thwaites (Araceae) leaves in the treatment of intestinal worm infections is a common ethnobotanical practice in the Naga tribes of India. In the current study, the anticestodal efficacy of L. spinosa. leaf extract was investigated against a tapeworm using Hymenolepis diminuta.–rat animal model. The anticestodal effects of L. spinosa. leaf extract was determined by monitoring the eggs per gram of feces (EPG) counts and percentage worm recovery rates after treatment with leaf extract in single and double doses of 200, 400, 800, and 1600 mg/kg that were given orally for 5 days to the rats harboring immature and mature worms. The effect of plant extract was found to be dose-dependent, and double doses showed better efficacy as compared with single doses. In the case of infections with immature worms, 1600 mg/kg double dose of L. spinosa. leaf extract reduced the fecal egg counts of H. dimunta. by 80.8% and worm recovery rate by 16.7%, respectively. Praziquantel, the standard anticestodal drug given in 5 mg/kg single dose, reduced the fecal egg count by 83.2% and worm recovery rate by 16.7%. In the case of efficacy against mature worms, 1600 mg/kg double dose of leaf extract reduced the fecal egg counts of H. diminuta. by 94.9% and worm recovery rate by 8.5%, respectively. Praziquantel (5 mg/kg, single dose) reduced the fecal egg counts by 95.1% and worm recovery rate by 16.7%. The study suggests that the leaf extract of L. spinosa. possesses significant anticestodal efficacy and supports its use in folk medicine.     

Disposition of flavodilol in laboratory animals

The disposition of flavodilol, a novel antihypertensive agent, was investigated in rats, rabbits, and dogs following iv or oral administration of 14C-flavodilol or unlabeled drug. Peak, plasma levels occurred within 6 hours of an oral dose in all three species. Following an iv dose, plasma elimination half-lives of flavodilol in rats, rabbits, and dogs were 3.0, 3.0, and 4.0 hr, respectively. Total body clearances were 0.71 liter/hr/kg for the rat, 1.89 liters/hr/kg for the rabbit, and 3.07 liters/hr/kg for the dog. Renal clearances were a small fraction of total clearance at 0.042, and 0.114 liter/hr/kg for the rat and dog, respectively, suggesting extensive nonrenal clearance. The volumes of distribution of 3.04 for the rat, 8.10 for rabbit, and 18.13 liters/kg for dog are large, suggesting significant extravascular distribution of flavodilol. Following 10 and 50 mg/kg po doses of 14C-flavodilol in rats, recovery of total radioactivity after 79 hr was 100.7% and 88.4% of the dose, respectively, most of which was recovered in the feces (77.5% and 66.6%, respectively). Tissue distribution studies of 14C in rats at 1.5, 5, 24, and 48 hr after a single po dose of 10 mg/kg 14C-flavodilol showed that the majority of the radioactivity was in the gastrointestinal tract and organs of elimination at all time points. Less than 1% of the dose remained in the body at 48 hr. 14C-Flavodilol was administered to rats iv at 1 mg/kg and orally at 10 mg/kg to assess comparative (label vs. nonlabel) absorption and distribution characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)     

OLTIPRAZ对小鼠日本血吸虫病的初步治疗

Oltipraz is a new drug against Schistosomiasis mansoni and was used to treat mice Schistosorniasis japonica in our laboratory. The results showed that 48 h after oral administraction of oltipraz at a single dose of 900 mg/kg, 97% Schistosomes in mice infected with Schistosomiasis japonica schifted to the liver of the host. About half of these worms returned to the mesenteric veins in 96 h. Infected mice was given oltipraz orally at the dose of 900 mg/kg.d for 3～5 days, and killed in 28 days after the last dose. Over 95% total worm reduction rate was found.Schistosomes in infected mice treated with oltipraz were collected for histological observation. The results showed that the tegument of schistosomes were damaged and host cells invaded into the worm body; and granuloma formation of dead worm was observed.During the treatment, food uptake and body weight of the infected mice were decreased, but regained soon after the cessation of the treatment.     

Evaluation of diazepam and pyridoxine as antidotes to isoniazid intoxication in rats and dogs

Because information regarding efficacious treatment of acute isoniazid (INH) toxicity is incomplete and controversial, diazepam and pyridoxine were investigated as iv antidotes in rats and dogs following administration of po lethal doses of INH. There is a marked species variation in the lethality of INH; the lowest consistently lethal dose is 1500 mg/kg for rats and 75 mg/kg for dogs. Of the two species, the dog more closely approximates man's sensitivity to the lethal effect of INH overdose (80–150 mg/kg). Species variation was also observed in the effects of the antidotes. Diazepam exerted dose-related protection against convulsions in rats; paradoxically, survival was increased by the lowest dose (1 mg/kg) but not by higher doses. In dogs, however, diazepam failed to prevent convulsions but provided dose-related protection against death. Pyridoxine, in rats, did not protect against INH toxicity, but in dogs it showed dose-related effectiveness against convulsions, and all doses (75–300 mg/kg) prevented lethality. Significantly, the highest dose of pyridoxine tested in rats (750 mg/kg) was substantially below the optimal pyridoxine-to-INH antidotal ratio recommended for man (a dose that at least equals the amount of INH ingested), but that dose of pyridoxine would be larger than its LD50 for rats. Combined administration of diazepam with pyridoxine protected against convulsions and death in rats and dogs. Used concurrently, the two antidotes are clearly synergistic for controlling the manifestations of experimental INH overdose. These results have important implications for the management of acute INH intoxication in man.     

Effect of artesunate and artemether against Clonorchis sinensis and Opisthorchis viverrini in rodent models

Food-borne trematodiasis is an emerging public health problem and there is a need to develop novel treatment options. We examined the in vivo efficacy of single oral doses of artesunate and artemether administered to rodents experimentally infected with either Clonorchis sinensis or Opisthorchis viverrini. Rats infected with adult C. sinensis were administered artesunate or artemether at doses of 75, 150 or 300 mg/kg. Hamsters infected with adult O. viverrini were administered artesunate or artemether at doses of 200, 400 or 600 mg/kg. Treatment efficacy was assessed according to reductions in worm burden compared with infected but untreated control animals. Worm burden reductions of 98.6-100% were found in C. sinensis-infected rats after a single dose of artesunate and artemether at 150 mg/kg. Administration of artesunate and artemether at a dose of 400mg/kg to O. viverrini-infected hamsters resulted in worm burden reductions of 77.6% and 65.5%, respectively. However, both drugs showed toxic effects when administered to O. viverrini-infected hamsters at a dose > or =400mg/kg. Our study demonstrates that artesunate and artemether possess excellent clonorchicidal activities in vivo. These findings provide a foundation for subsequent clinical trials. More laboratory investigations are warranted to investigate further the opisthorchicidal properties of the artemisinins.     

Mediation of the schistosomicidal effect of praziquantel through nitric oxide

The effect of praziquantel (CAS 55268-74-1) on serum nitrate/nitrite level (a marker for nitric oxide (NO) synthesis) in S. mansoni infected mice was studied. The effects of the NO precursor (L-arginine) and NO-synthase inhibitor (NG-nitro-L-arginine methyl ester, L-NAME) on the effect of praziquantel on nitrate/nitrite level as well as on its antischistosomal activity were also evaluated. Praziquantel increased nitrate/nitrite level in serum of infected mice in a dose dependent manner. An oral dose of 75 mg/kg praziquantel produces a significant (p < 0.05) increase in serum nitrate/nitrite level by about 3.5 fold. Administration of L-arginine (200 mg/kg orally) induced a significant (p < 0.05) increase in nitrate/nitrite level (to about 5 fold) compared to praziquantel 75 mg/kg alone. Praziquantel-induced increase in nitrate/nitrite level was significantly reduced by administration of L-NAME 100 mg/kg. The antischistosomal activity of praziquantel was evaluated using two models: hepatic shift model and reduction of worm burden. In the hepatic shift model, praziquantel increased the percentage of worms in the liver (from 5% in control to 60%). Praziquantel-induced hepatic shift was not significantly affected by concurrent L-arginine or L-NAME administration. In the second model, praziquantel induced a significant decrease of the worm burden (p < 0.05) and the action of praziquantel was significantly increased by L-arginine and reduced by L-NAME administration. In conclusion, NO is possibly involved in the antibilharzial effect of praziquantel and administration of L-arginine with praziquantel produces beneficial antibilharzial effect.     

Prior administration of a low dose of thioacetamide protects type 1 diabetic rats from subsequent administration of lethal dose of thioacetamide

Previously, we reported that an ordinarily non-lethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic rats due to inhibited liver tissue repair, whereas 30 mg TA/kg allows 100% survival due to stimulated although delayed tissue repair. Objective of this investigation was to test whether prior administration of a low dose of TA (30 mg/kg) would lead to sustainable stimulation of liver tissue repair in type 1 diabetic rats sufficient to protect from a subsequently administered lethal dose of TA. Therefore, in the present study, the hypothesis that preplacement of tissue repair by a low dose of TA (30 mg TA/kg, ip) can reverse the hepatotoxicant sensitivity (autoprotection) in type 1 diabetic rats was tested. Preliminary studies revealed that a single intraperitoneal (ip) administration of TA causes 90% mortality in diabetic rats with as low as 75 mg/kg. To establish an autoprotection model in diabetic condition, diabetic rats were treated with 30 mg TA/kg (priming dose). Administration of priming dose stimulated tissue repair that peaked at 72h, at which time these rats were treated with a single ip dose of 75 mg TA/kg. Our results show that tissue repair stimulated by the priming dose enabled diabetic rats to overexpress, calpastatin, endogenous inhibitor of calpain, to inhibit calpain-mediated progression of liver injury induced by the subsequent administration of lethal dose, resulting in 100% survival. Further investigation revealed that protection observed in these rats is not due to decreased bioactivation. These studies underscore the importance of stimulation of tissue repair in the final outcome of liver injury (survival/death) after hepatotoxicant challenge. Furthermore, these results also suggest that it is possible to stimulate tissue repair in diabetics to overcome the enhanced sensitivity of hepatotoxicants.     

Attenuation of scopolamine-induced amnesia in mice

The dose-response effects of the substituted xanthine 8-cyclopropyltheophylline (CPRT) on sleep and wakefulness (W) after intraperitoneal administration to rats were examined by means of simultaneous electroencephalographic (EEG) and electromyographic (EMG) recordings. Doses of 20 and 40 mg/kg CPRT increased W and decreased slow wave sleep (SWS) in rats, indicating CNS stimulant effects. The greatest CNS stimulation was produced by the lowest (20 mg/kg) dose of CPRT examined, which also increased the latency to SWS. In addition, the 20 mg/kg dose of CPRT also significantly decreased the amount of total sleep (TS), as compared to the vehicle group, during all time periods examined. In contrast, the 80 mg/kg dose of CPRT decreased W and increased both SWS and TS. However, this apparent hypnotic effect of the 80 mg/kg CPRT may be due to toxicity, since 80% of rats treated with this dose of the drug died within 48 h of injection.     

Pre-clinical toxicity studies on the new nitroimidazole 1-methylsulphonyl-3-(1-methyl-5-nitroimidazole-2-yl)-2- imidazolidinone

Administration of 1-methylsulphonyl-3-(1-methyl-5-nitro-2-imidazole-yl)-2-imidazolidinone (Go 10213) at a dose of 5000 mg/kg to rat, mouse, guinea pig and rabbit and 3000 mg/kg to dog did not induce any toxic symptoms or mortality. Repeated daily gavaging with doses ranging from 50-3000 mg/kg/day were tolerated by rats for 2 weeks. No mortality was noticed in treated animals. Reduction in weight gain was observed in male rats on 2000 mg/kg per day and females on 1000 mg/kg per day. No toxic changes were noticed in dogs treated with 200 mg/kg per day for 2 weeks. One monkey treated with 75 mg/kg per day for 4 weeks tolerated the compound without exhibiting any toxic effects. No drug induced alterations were noticed in rats gavaged with 60 and 200 mg/kg per day for 4 weeks. Rats treated with a daily dose of 600 mg/kg showed reduction in body weight gain and atrophy of testes and these changes were reversible after stopping of medication. Dogs medicated with 30 and 100 mg/kg per day tolerated the drug for 4 weeks. Except slight ataxia in a few dogs treated with 100 mg/kg per day, no other drug induced toxic effects were noticed. Neurological symptoms were noticed in all dogs on high dose of 200 mg/kg. Three animals out of six were sacrificed in extremis in this dose. After discontinuation of Go 10213 all dogs on 100 and 200 mg/kg per day recovered normal gait in about a week. No definitive drug induced changes were noticed in laboratory investigations, gross and histopathological examinations.(ABSTRACT TRUNCATED AT 250 WORDS)