Praziquantel is the only effective drug of choice against five huaman species of schistosomes. Main adva-ntages of praziquantel include convenient oral administration, high safety and efficacy as well as short treatment course. To better understand the mode of action of praziqantel against schistosomes would be helpful for further development of new broad-spectrum anthelminthics. This paper summarizes the 30 years′ research progress on the mode of action of the drug against schistosomes proceeded by domestic and abroad laboratories.

Experimental studies indicated that the killing process of schistosomes induced by praziquantel comprises two aspects, i.e. the direct effect of praziquantel on schistosomes and the host immune reaction. The former one appears in stimulation of worm activity, spasmodic contraction of worm musculatures and severe damage to the tegument, which results in hepatic shift of schistosomes, influence on the nutrition absorption, excretion/secretion and defense function of the tegument, followed by the secondary interference with the worm metabolism. While the latter one involves the destruction of the host concomitant immune mechanism after tegumental damage and peeling, which is unfavorable for worm survival. Particularly, the exposure of the worm surface antigen provides a target which can be attacked by specific antibodies. Therefore, the antischistosomal activity of praziquantel is immune-dependent. In this paper some host factors involved in the killing process of schistosomes induced by praziquantel were summarized.

This paper summarizes the progress in the study on anthelmintics,including nematocide,trematocide and cestocide since the founding of the People′ s Republic of China and the roles that these agents played in the control of parasitic diseases.Meanwhile,views are given to the challenges faced in the further study on anthelmintics.

Currently praziquantel is one of the major drugs used in treatment of schistosomiasis and other trematode infections.Recent experimental studies indicate that a new anthelmintic,tribendimidine,is used in the treatment of intestinal nematodes,also possesses effect against several species of trematodes including Clonorchis sinensis,Opisthorchis viverrini and Echinostoma caproni.Tribendimidine is even more effective against C.sinensis in rats that a single 300 mg/kg oral dose cures almost all of the animals treated,a lower cure dose than praziquantel(375-500 mg/kg).The anti-malarial drugs artemether and artesunate are not only effective in the prevention of schistosomiasis,but also effective against several species of trematodes,especially C.sinensis.The single oral dose of both drugs to cure or achieve high efficacy in infected rats is 75 mg/kg.This review summarized research progress on tribendimidine,artesunate,and artemether in experimental animals infected with C.sinensis and other species of trematodes.

Objective To explore the regularity of damage of anti-lipid peroxidation by air pollutants, and to provide experimental basis for revealing the pathogenetic mechanism of air pollutants. Methods 80 Wistar rats weighting 180-200 g were randomly and averagely divided into 4 groups, ie control group, lower dose group, middle dose group and higher dose group, which were exposed to particulate, SO2 and NO2 respectively. The rats in lower dose group, middle dose group and higher dose group were perfused by 1 ml normal saline mixed with 7.5, 15 and 30 mg particulate respectively, while the rats in control group were only perfused with 1 ml normal saline. At the 2nd day after exposure to particulate, the rats in 3 dose groups were exposed to the mixed air of SO2 and NO2. The lower, middle, and higher dose group were exposed to mixed air of SO2 and NO2 at the concentrations as following: 8 and 5 mg/m3, 16 and 10 mg/m3, 32 and 20 mg/m3 respectively while the control group was exposed to fresh air two hour per day, continuously for 7 days. Half of the rats in each dose group were killed at the 1st day after the 7-day exposure to SO2 and NO2 , the rest were killed at the 8th day after the 7-day exposure to SO2 and NO2 . The contents of MDA, the activities of GST and SOD in serum, the activities of SOD and the contents of MDA in BALF were measured. Results At the 1st day after the exposure to SO2 and NO2 , lower activities of SOD and GST, and higher contents of MDA in serum of rats were observed in higher dose group compared with those in control group. At the 8th day after the exposure to SO2 and NO2 , significantly lower SOD activities were still observed in higher dose group compared with those in control group. It revealed that higher concentrations of air pollutants could decrease the activities of anti-oxidase and increase the contents of lipid peroxides in serum of rats. However, the SOD activities in BALF showed no significant differences among different dose groups at different time during the exposure period. Higher contents of MDA in BALF of rats were observed in higher dose group at the first day after the exposure to SO2 and NO2 , and in middle and higher dose group at the 8 th day after the exposure to SO2 and NO2 compared with those in control group (P

Objective To explore the therapeutic effect of artemether and artesunate on adult Schistosoma mansoni in experimental mice.Methods The mice were administered intragastrically with artemether or artesunate 46 days after being infected with cercariae of S.mansoni subcutaneously. On Day 1,a dose of 400, 300, 200 mg/kg of artemether or artesunate was administered to the mice. From Day 2 to Day 7, a half above dose was administered. On Day 7, the single-dose groups were administered with artemether or artesunate at the dose of 1600, 1200, 800 mg/kg, meanwhile, an infected group of mice was served as control, untreated. Results With 7-day therapy of artemether at the dosage of 1600, 1200, 800 mg/kg, the worm reduction rates were 53%, 49% and 53%, respectively, and female worm reduction rates were from 78%-82%, compared with the control group.The therapeutic effects of artemether on single-dose groups were similar. The worm reduction rates, with 7-day therapy of artemether at the dosage of 1600, 1200, 800 mg/kg , were 16%,37% and 49%, respectively, compared with the control group. Conclusion The efficacy of therapy with artemether and artesunate on S.mansoni infection mice were relatively well. Concerning the therapeutic effect and toxicity, artemether is slightly better than artesunate.

Objective:To investigate the effect of silver diamine fluoride(SDF)on the bonding strength between dentine and glass ion-omer cement(GIC).Methods:1 2 extracted sound molars were prepared into dintine samples and distributed into sound dentine group and demineralized dentine group.According to the treatment methods,the samples in each group were respectively divided into 3 sub-groups:A(control group),B[coated with 38% Ag(NH3 )F2 ]and C(SDF treatment with additional lighting-curing)(n =20).Then a hand-mixed conventional glass ionomer cement Fuji IX was placed on the dentine surface.After 24 h,micro tensile bond strength test and scanning electron microscope (SEM)analysis were conducted.Results:The bonding strength of demineralized dentine was higher than that of sound dentine(P <0.01 ).SDF with additional lighting-curing treated dentine showed a higer bonding strength value than only SDF treated dentin(P <0.01 ).Conclusion:SDF may improve the bonding between dentine and GIC.

Objective To assess the effect of artemether on the tegument of adult Schistosoma haematobium harbored in mice. Methods Ten mice were infected subcutaneously with 100-120 S. haematobium cercariae each. At day 81 post-infection, 8 mice were treated orally with 400 mg/kg artemether. Mice were sacrificed at 1, 3, 7 and 14 days post-treatment, and schistosomes were collected by the perfusion technique, fixed and examined under a scanning electron microscope. Schistosomes obtained from the 2 untreated mice served as a control. Results Twenty-four hours post-treatment, tubercles on the tegument of male worms showed lesions, characterized by enlargement, collapse and partial peeling off from the border with the tegument. In both male and female worms, the tegument showed focal or extensive swelling, fusion, vacuolization, erosion, peeling, and destruction of sensory structures. Three days post-treatment,tegumental alterations further aggravated; particularly severe damage was the swelling or collapse of the oral sucker observed in both sexes. In addition, extensive swelling, erosion and peeling of tegumental ridges and destruction of discoidlike sensory structures were seen in female worms. Seven to 14 days post-treatment, moderate-to-severe damage was still evident in some worms, whereas other worms surviving the treatment showed apparent recovery in most parts of their tegument. Conclusion Artemether causes extensive and severe tegumental damage in adult S. haematobium.

Objective To perform a temporal examination of ultrastructural alterations in adult Schistosoma haematobium due to artemether Methods Eight mice infected with 100-120 S. haematobium cercariae for 81 days were treated intragastrically with 400 mg/kg artemether. At 24 hours, 3, 7 and 14 days post-treatment, groups of 2 mice were sacrificed and schistosomes collected by the perfusion technique. Worm samples were fixed and examined by transmission electron microscopy. Schistosomes were also obtained from 2 untreated mice that served as control.Results Typical ultrastructural alterations included swelling, lysis and vacuolization of the tegumental matrix, and disappearance of basal membrane. In sensory organelles and tubercles, there was extensive or local lysis of internal structure. In the musculature, parenchymal tissues, syncytium and gut epithelial cells, focal or extensive lysis, decrease in granular endoplasmic reticulum, vacuolization and degeneration of mitochondria were observed. These alterations became apparent both in male and female worms 24 hours post-treatment. In female worms, severe damage to the vitelline cells was also observed, resulting in the emergence of vacuoles, a decrease in granular endoplasmic reticulum,fusion of vitelline balls or even collapse of damaged vitelline cells. The most extensive tegumental alterations were observed 3-7 days post-treatment. Whilst 14 days post-treatment ultrastructural damage was still apparent, the tegument of some worms showed similar features to those recovered from untreated control mice. Conclusion Administration of artemether to mice infected with adult S. haematobium results in extensive damage to the ultrastructure in the tegument and subtegument tissues of the worms, confirming previous results with other schistosome species.

Objective To study the effect of artemether (Art) on total antioxidant capacity (T-AOC) in adult Schistosoma japonicum. Methods In vitro, the T-AOC was determined in five-week old worms incubated without or with Art and/or hemin for 24 h, and the worms were continuously incubated for 96 h, then worm survival was assessed. In vivo, T-AOC was determined in worms freshly recovered from mice 6 - 24 h after treatment with Art 300 mg/kg. Results Throughout 96 h incubation no worms were killed by 50 μmol/L Art or 50 μmol/L hemin alone, but approximatdy 80% of them were killed by Art plus hemin. Addition of reduced glutathione and vitamin E could significantly block the cidal action of the combined treatment. No effect on T-AOC was seen in the worms exposed to Art or heroin alone for 24 h, but the combined treatment led to a pronounced T-AOC reduction in female worms in vitro. Such a drug effect on female worms was demonstrated in vivo. After female worms were exposed to Art for 6 - 24 h in vivo, their T-AOC was significantly reduced by 40% - 64%. However, no drug effect on male worms' T-AOC was observed in vivo and in vitro exposed to Art plus hemin. Conclusion Art-induced T-AOC reduction in female worms may sensitize them to lethal damages of endogenous and exogenous oxygen radicals.