[3H]吡喹酮在不同发育期血吸虫体内的分布

前文指出,不同发育期的血吸虫对吡喹酮的敏感性有所不同。对虫形态的观察结果表明,这种敏感性的差别主要表现在虫的体表是否受损、受损的程度,以及受损后能否修复等。这一推断亦为用间接荧光抗体法检测虫的体表抗原显露的结果所支持。本文进一步观察[~3H]吡喹酮在不同发育期血吸虫体内的分布是否有差异。     

吡喹酮对21-d日本血吸虫童虫皮层损害的扫描电镜观察(英文)

目的:观察吡喹酮对21-d童虫皮层的作用.方法:小鼠于感染日本血吸虫尾蚴达21 d时,ig1剂吡喹酮,并在治疗后1-48 h的不同时间内剖杀取虫,作扫描电镜观察.结果:吡喹酮的剂量为300 mg·kg~(-1)时,宿主体内的21-d童虫示有轻度或中度的皮层褶嵴肿胀、融合、糜烂或破溃,且以盘状感觉器的肿胀为特征.用吡喹酮的较高剂量500 mg·kg~(-1)治疗,虫的体表亦有相似的变化,但较广泛和严重.若每d ig吡喹酮500 mg·kg~(-1),连给3 d,则虫的皮层严重肿、糜烂和剥落,并伴有宿主的白细胞附着.结论:结果表明,吡喹酮对21-d童虫有直接杀死作用.     

吡喹酮引起的日本血吸虫体表皮层的损害和宿主白细胞侵入虫体的观察

感染日本血吸虫的小鼠一次口服吡喹酮300mg/kg后0.5小时,雄虫体表皮层即有不同程度的水肿、空泡样变化和空泡破裂,继则有细絮状物或絮状团块粘附在受损的体表或抱雌沟内。给药6小时后即见有白细胞附着在受损的皮层上,12小时后则已有白细胞侵入虫体。雌虫体表皮层的损害和出现白细胞附着与侵入虫体的时间较雄虫为迟。此外,对血吸虫经吡喹酮作用后,其皮层的损害和白细胞的附着与侵入虫体的意义进行了一些讨论。     

吡喹酮引起的日本血吸虫体表皮层的损害和宿主白细胞侵入虫体的观察

感染日本血吸虫的小鼠一次口服吡喹酮300mg/kg后0.5小时,雄虫体表皮层即有不同程度的水肿、空泡样变化和空泡破裂,继则有细絮状物或絮状团块粘附在受损的体表或抱雌沟内。给药6小时后即见有白细胞附着在受损的皮层上,12小时后则已有白细胞侵入虫体。雌虫体表皮层的损害和出现白细胞附着与侵入虫体的时间较雄虫为迟。此外,对血吸虫经吡喹酮作用后,其皮层的损害和白细胞的附着与侵入虫体的意义进行了一些讨论。     

吡喹酮对日本血吸虫皮层损害的扫描电镜观察

给感染血吸虫病的小鼠一次灌胃吡喹酮300 mg/kg后10分钟至48小时,自鼠肝内取虫作体表皮层扫描电镜观察。结果表明,干给小鼠药后10分钟,两性血吸虫皮层即有变化,1～2小时后已十分明显,主要变化为水肿,皮层褶嵴紧密连接、融合,形成大量球状物或小泡,感觉器肿大、破溃,以及皮层糜烂、剥落和白细胞附着于皮层损害处等。     

吡喹酮抗日本血吸虫雄虫过程中免疫血清的作用

体内或体外培养的血吸虫雄虫经一定浓度的吡喹酮作用后,移置含免疫血清的培养液中培养时,受损害的虫体体表有大量絮粒状物沉积,形成膜状包被,加重皮层的损害;在继续培养3天时,大部分或全部虫未见有明显恢复。若将虫移置含正常血清的培养液中培养时,则无此种现象,且大部虫的体表损害有不同程度的恢复。上述结果亦为扫描电镜的观察所证实。     

吡喹酮预防小鼠感染日本血吸虫尾蚴的分析

小鼠一次口服吡喹酮200～600 mg/kg后,对感染血吸虫有保护作用。感染后15min至2h,自这些小鼠感染部位的皮肤分离的童虫,部分或大部分已死亡。另一方面,钻穿服药鼠离体皮肤的尾蚴数亦明显减少。进一步分析的结果表明,在水中,血吸虫尾蚴对吡喹酮极其敏感。由于小鼠口服吡喹酮后,药物可自其皮肤排泌,故以水涂擦皮肤时,溶于水中的吡喹酮即对血吸虫尾蚴起作用,并认为这是吡喹酮产生预防作用的主要原因。     

吡喹酮预防小鼠感染日本血吸虫尾蚴的分析

小鼠一次口服吡喹酮200～600 mg/kg后,对感染血吸虫有保护作用。感染后15min至2h,自这些小鼠感染部位的皮肤分离的童虫,部分或大部分已死亡。另一方面,钻穿服药鼠离体皮肤的尾蚴数亦明显减少。进一步分析的结果表明,在水中,血吸虫尾蚴对吡喹酮极其敏感。由于小鼠口服吡喹酮后,药物可自其皮肤排泌,故以水涂擦皮肤时,溶于水中的吡喹酮即对血吸虫尾蚴起作用,并认为这是吡喹酮产生预防作用的主要原因。     

抗童虫表膜单克隆抗体与吡喹酮协同杀血吸虫作用

目的为观察抗血吸虫童虫表膜单克隆抗体与吡喹酮协同杀灭血吸虫的作用。方法用药物加单克隆抗体被动转移小鼠试验，计算小鼠抗攻击感染的减虫率和减卵率。结果在单抗被动转移小鼠感染3d后加吡喹酮组，其减虫率减卵率分别为91.9％和90.3％，均明显高于单用药物组17.2％、26.9％的减虫率和减卵率;在单抗被动转移小鼠感染38d后加吡喹酮组，其减虫率、减卵率分别为96.9％和83.4％，亦明显高于单用药物组84.9％、31.9％的减虫率和减卵率。结论被动转移的单抗与吡喹酮表现为一种明显的协同杀虫减卵作用。宿主免疫水平的高低明显影响吡喹酮的杀虫作用，提高宿主体内特异性抗体水平，可显著加强吡喹酮预防血吸虫感染和杀灭血吸虫的作用。     

用吡喹酮治疗家兔血吸虫病时宿主免疫水平与疗效的关系

家兔感染日本血吸虫尾蚴3至10周,用吡喹酮40 mg/kg ig 1次治疗时,疗效以感染3周组的为最差,感染5周组的疗效明显增加,而以感染8及10周组的最好,全部或大部分受治兔的雌虫被杀灭。这一结果与宿主特异性抗体的有无和抗体水平的增长相一致,而与细胞的免疫水平则无密切的平行关系。进一步的试验结果表明,吡喹酮对虫龄为3周童虫的疗效与特异性抗体的存在有密切关系。     

Ethoxyresorufin-O-deethylase (EROD) inducing potencies of planar chlorinated aromatic hydrocarbons in primary cultures of hepatocytes from different developmental stages of the chicken

In vitro induction of ethoxyresorufin O-deethylase (EROD) activity in cell cultures is an extensively validated tool for measuring overall potencies of mixtures of halogenated aromatic hydrocarbons (HAHs) in samples from the abiotic or biotic environment. For risk assessment with special attention to effects in wild birds, an assay was developed that makes use of chicken embryo hepatocytes. However, it was questioned whether compound-specific responses are consistent at the various developmental stages. The results of our present study show that there are considerable differences between early and late embryonal and post-hatching stages. The induction of EROD was measured in primary chicken hepatocyte cultures. The cells were isolated at day 14 and day 19 of embryonal development and at day 1 post hatching. Hepatocytes were exposed in vitro to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126, IUPAC nomenclature) and 2,3′,4,4′,5-pentachlorobiphenyl (PCB 118). The respective compounds were chosen as representives for dioxins, furans, non-ortho PCBs, and mono-ortho PCBs. These groups of chemicals have been identified as environmental contaminants with major dioxin-like effects that are mediated by a common receptor, the arylhydrocarbon (Ah) receptor. At all developmental stages, TCDF was more potent than TCDD. Relative potencies (RP = EC50tcdd/EC50hah) decreased in the order TCDF<TCDD< PCB 126<PCB 118. Depending on the developmental stage, TCDF was 1.2 to 3.4 times more potent than TCDD. PCB 126 was equipotent or less potent by a factor of 3 than TCDD. PCB 118 was 100 to 300 times less potent than TCDD. Both the mean effective concentration (EC₅₀) and the maximum EROD activity (Y _max) of all compounds were lower in hepatocyte cultures from 14-day-old embryos than those from 19-day-old embryos or 1-day-old hatchlings. RPs were comparable in 19-day-old embryos and in hatchlings, but significantly different in 14-day-old embryos. Received: 13 March 1997 / Accepted: 9 July 1997     

高压液相法测定家兔用吡喹酮后的血药浓度及药代动力学参数

本文报道用高压液相法测定家兔用吡喹酮后的血药浓度及药代动力学参数。方法条件:青岛硅胶(5～10μm)柱作吸附层析;正丁醇—氯仿—乙酸乙酯—10%氨水(20:20:60:3)作流动相。荧光检测:λ_ex260nm,λ_em285nm。检测限为20ng吡喹酮,线性范围为0.1～0.9μg/ml血浆。家兔静注吡喹酮后K_α=3.00h^-1,t_1/2(α)=0.23h,K_el=0.28h^-1,t_1/2(β)=2.48h。家兔口服吡喹酮片剂及胶囊后,胶囊的相对生物利用度为片剂的74.8%。     

Calorimetric study of tryptophan synthase α-subunit and two mutant proteins

Heat-denaturation of tryptophan synthase α-subunit from E. coli and two mutant proteins (Glu 49 ± Gln or Ser; called Gln 49 or Ser 49, respectively) has been studied by the scanning microcalorimetric method at various pH, in an attempt to elucidate the role of individual amino acid residues in the conformational stability of a protein. The partial specific heat capacity in the native state at 20°, C_p²⁰, has been found to be (0.43 ± 0.02) cal ± K^-1 ± g^-1, the unfolding heat capacity change, Δ_dC_p, (0.10 ± 0.01) cal ± K^-1 ± g^-1, and the unfolding enthalpy value extrapolated to 110°, Δ_dh¹¹⁰, (9.3 ± 0.5) cal ± g^-1 for the three proteins. The value of C_p²⁰ was larger than those found for fully compact protein and that of Δ_dh¹¹⁰ was smaller. Unfolding Gibbs energy, Δ_dG at 25° for Wild-type, Gln 49, and Ser 49 were 5.8, 8.4, and 7.1 kcal ± mol^-1 at pH 9.3, respectively. Unfolding enthalpy, Δ_dH, of the three proteins seemed to be the same and equal to (23.2 ± 1.2) kcal ± mol^-1 at 25°. As a consequence of the same value of Δ_dH and the different value in Δ_dG, substantial differences in unfolding entropy, Δ_dS, were found for the three proteins. The values of Δ_dG for the three proteins at 25° coincided with those from equilibrium methods of denaturation by guanidine hydrochloride.     

Anthelmintic efficacy of Clerodendrum viscosum on fowl tapeworm Raillietina tetragona

Context: Clerodendrum viscosum Vent. (Verbenaceae) is a shrub, widely used amongst the natives of India against various diseases.

Objective: Crude extract of the plant was tested in vitro on a tapeworm Raillietina tetragona Molin (Davaineidae) to evaluate its potential anthelmintic efficacy and ultrastructural changes in the parasite.

Materials and methods: Parasites were exposed to different concentrations of ethanolic leaf extract (10–80?mg/mL) and praziquantel (0.0005–0.005?mg/mL) and incubated in phosphate-buffered saline (PBS). The pH was 7.4 at 37?°C, while one set of worms was incubated only with PBS as a control. Permanent immobilization of worms was determined visually when no motility occurred on physically disturbing them. The parasites exposed to high concentrations of leaf extract and praziquantel treatments were processed for histological and electron microscopic studies, as these concentrations took the least time for paralysis and death to occur.

Result: With an increase in the concentration of the leaf extract from 10 to 80?mg/mL and praziquantel from 0.0005 to 0.005?mg/mL, the time for the onset of paralysis and death was shortened. The treated parasites lost their spontaneous movement rapidly followed by death. Electron microscopic observations revealed disruptions in the tegument and parenchymal layer, accompanied by deformities in cell organelles.

Discussion and conclusion: Extensive structural alterations in the tegument indicate that the plant-derived components cause permeability changes in the parasite leading to paralysis and subsequent death. These observations suggest that phytochemicals present in C. viscosum have vermifugal or vermicidal activity, and thus may be exploited as alternative chemotherapeutic agents.     

Comparative studies on the anorectic activity of d-fenfluramine in mice,rats, and guinea pigs

Summary The present study compares the anorectic activity of d-fenfluramine and its metabolite d-norfenfluramine in three animal species. d-Fenfluramine and d-norfenfluramine show anorectic activity at increasing doses (ED₅₀) in rats, guinea pigs, and mice, d-norfenfluramine being more active than d-fenfluramine in all three species. Equiactive anorectic activities are reached with different brain levels of d-fenfluramine and d-norfenfluramine, guinea pigs being the most sensitive species, followed by rats then mice. The metabolite most probably plays a major role in the anorectic effect of d-fenfluramine in guinea pigs, contributes to the anorectic activity in rats, but adds little to the action of the parent drug in mice. The different sensitivity to d-fenfluramine and d-norfenfluramine in these three species does not appear to be explained by a number of biochemical parameters, including serotonin uptake or release, receptor subtypes, or ³H-d-fenfluramine binding and uptake. Send of fprint requests to T. Mennini at the above address     

Synthesis of praziquantel derivatives and theirin vitro activity against adultClonorchis sinensis

Several praziquantel derivatives have been prepared by the acylation of compound5, and examined on their biological activityin vitro against adultClonorchis sinensis collected from rabbits infected with metacercariae which was isolated fromPseudorasbora parva, a second intermediate host, captured in Nakdong river in Korea.     

Altered sensitivity to d-methylamphetamine,apomorphine, and haloperidol in rhesus monkeys depleted of caudate dopamine by repeated administration of d-methylamphetamine

The long-term neurochemical and behavioral effects of repeated d-methylamphetamine (d-MA) administration were investigated using four male rhesus monkeys trained to lever-press for food on a DRL-40 s schedule of reinforcement. Dose-response curves for d-MA (0.0625–2.0 mg/kg), apomorphine (0.025–0.4 mg/kg), and haloperidol (0.005–0.04 mg/kg) on responding showed that repeated d-MA administration (0.5–16.0 mg/kg/day) decreased sensitivity to d-MA and to apomorphine but increased sensitivity to haloperidol. At 3–6 months after the last injection of d-MA, a 48.1% decrease in caudate dopamine (DA) was observed, with the frontal cortex, midbrain, and ponsmedulla showing no significant change. A trend toward increasing concentrations of norepinephrine was noted in the same brain areas, but only in the frontal cortex did this change reach significance. Specific binding of 3H-spiroperidol to caudate membrane preparations was not changed, while the V _max of the caudate DA re-uptake process declined 32%, with no change in K _m. These results suggest that exposure of DA neurons in the caudate nucleus to high concentrations of d-MA can lead to nerve terminal degeneration.