Effect of artemether on glucose uptake and glycogen content in Schistosoma japonicum.
AIM: To study the effect of artemether (Art) on glucose uptake and glycogen content in schistosomes. METHODS: Schistosomes recovered from mice treated intragastrically with Art 300 mg.kg-1 for 24-48 h, were incubated in the drug-free medium containing [U-14C]glucose 11.1 MBq.L-1. The glycogen content, [U-14C]glucose uptake, and incorporation of [U-14C]glucose into worm glycogen in both male and female worms were determined. RESULTS: When above-mentioned schistosomes were exposed to drug-free medium containing [U-14C]glucose for 1-24 h, the glycogen contents of male and female worms decreased 27%-61% and 39%-78%, respectively. Only 3 out of 6 male worm groups showed 23%-35% decrease in glucose uptake, while much less glucose uptake was found in female worms in all groups with reduction rates of 18%-38%. Apart from 2 male groups no apparent change in the incorporation of [U-14C]glucose into the worm glycogen was seen. CONCLUSIONS: Art-induced glycogen reduction in schistosomes was related to an inhibition of glycolysis rather than an interference with glucose uptake. (+info)
Inhibitory effect of artemether on proteinase of Schistosoma japonicum.
AIM: To study the effect of artemether (Art) on the thio proteinase ("hemoglobinase", Hem) of Schistosoma japonicum. METHODS: Hem was extracted from S japonicum adults. The inhibitory effect of Art on the activity of Hem to degrade human hemoglobin (Hgb) was examined with UV-photometer at 280 nm, SDS-PAGE and scanning at 600 nm on a chromoscanner. RESULTS: Human Hgb was degraded at pH 4.0 by the Hem. The activities of Hem preincubated at 37 degrees C with Art 0.14, 1.4, and 14 mmol.L-1, were inhibited by 30.2%, 39.8%, and 45.0%, respectively. CONCLUSION: Art possesses an inhibitory effect to Hem of S japonicum. (+info)
Egg laying is delayed but worm fecundity is normal in SCID mice infected with Schistosoma japonicum and S. mansoni with or without recombinant tumor necrosis factor alpha treatment.
Mice with severe combined immunodeficiency (SCID mice) lack functional B and T cells. Egg laying by Schistosoma mansoni and S. japonicum was delayed in SCID mice, but in a matter of weeks worm fecundity was equivalent to that in intact mice. SCID mice formed smaller hepatic granulomas and showed less fibrosis than did intact mice. The reduction in egg-associated pathology in SCID mice correlated with marked reductions in interleukin-4 (IL-4), IL-5, IL-13, and gamma interferon mRNA expression in the liver. S. mansoni infections were frequently lethal for SCID mice infected for more than 9 weeks, while S. japonicum-infected SCID mice died at the same rate as infected intact mice. We were unable to affect hepatic granuloma formation or egg laying by worms in SCID mice by administration of recombinant murine tumor necrosis factor alpha (TNF-alpha). In fact, SCID and BALB/c mice appeared to express nearly equivalent levels of TNF-alpha mRNA in their granulomatous tissues, suggesting that there is little or no deficit in TNF-alpha expression in infected SCID mice. The data indicate that TNF-alpha may be in large part derived from a non-T-cell source. Together, these findings provide little evidence that TNF-alpha alone can reconstitute early fecundity, granuloma formation, or hepatic fibrosis in schistosome-infected SCID mice. (+info)
Evidence for an improvement in cognitive function following treatment of Schistosoma japonicum infection in Chinese primary schoolchildren.
A double-blind, placebo-controlled, treatment trial was conducted in Sichuan, China to investigate the unique and combined effects on the cognitive function (working memory) of children after treating geohelminth infections with albendazole and treating Schistosoma japonicum infection with praziquantel. One hundred eighty-one children 5-16 years of age participated. At baseline, the praziquantel and placebo groups were similar in all background characteristics. Three months after praziquantel treatment, there was a significant reduction in the prevalence and intensity of S. japonicum infection. There were significant age group by praziquantel treatment interaction effects in three of the five cognitive tests, Fluency, Picture Search, and Free Recall, with effects being strongest in the youngest children (5-7 years old). Exploratory analysis within the youngest children showed a significant positive main effect of treatment on Fluency (P < 0.001), after controlling for sex, anthropometric, and parasitic and iron status. There was also a treatment by height-for-age interaction (P = 0.03) and a treatment by iron status interaction (P = 0.024) on Fluency. There was a treatment by S. japonicum intensity interaction (P < 0.001) on Free Recall, but the main effect of treatment on Picture Search was not significant (P = 0.058). Younger children and those who are physically the most vulnerable are likely to benefit the most from the treatment of S. japonicum infection in terms of improved performance on tests of working memory. (+info)
Characterisation of a family of Schistosoma japonicum proteins related to dynein light chains.
Dynein light chains (DLC) are components of dynein, an enzyme complex involved in various aspects of microtubule-based motility. We report here the molecular cloning and sequencing of cDNAs encoding a family of DLC-like polypeptides (SjcDLC1-5) from the human bloodfluke Schistosoma japonicum with open reading frames of 87-104 amino acids and deduced molecular masses ranging from 10.5 to 12.3 kDa. Two-dimensional Western blot analysis confirmed the presence of several S. japonicum DLC isoforms with differing pI values and molecular sizes. We also describe the molecular characterisation, genomic organisation and expression of clone SjcDLC1, and the immunological characterisation and localisation of its encoded protein. Northern blot analysis of adult worm RNA indicated SjcDLC1 is encoded by a single message of approximately 650 bp and Southern analysis suggested one SjcDLC1 gene exists in the S. japonicum genome. Immunolocalisation studies demonstrated that the SjcDLC1 protein is present in the tegument of the adult and cercarial stages of S. japonicum. SjcDLC1 and the other SjcDLC may function in the transport of specialised organelles, comprising membranous and discoid bodies, through the tegument to the schistosome-unique heptalaminate tegumental membrane at the external surface of the adult worm. As a consequence, they may provide novel targets for anti-schistosome vaccine and/or drug development. (+info)
Effect of artemether on glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and pyruvate kinase of Schistosoma japonicum harbored in mice.
AIM: To study the effect of artemether (Art) on glyceraldehyde-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK), and pyruvate kinase (PK) of S japanicum. METHODS: Mice infected with schistosome cercariae for 32-38 d were treated ig with Art 100-300 mg.kg-1 and killed 24-72 h after medication for collection of schistosomes. The activities of GAPDH, PGK, and PK of the worms were determined by measuring the formation of NADH or consumption of NAD. The lactate content of the worms was also measured. RESULTS: After the infected mice were treated ig with Art 300 mg.kg-1 for 24 h, the inhibition rates of GAPDH were 13% (Male) and 21% (Female), and 48 h later the inhibition rates of the enzyme were 6% (Male) and 28% (Female). When Art 300 mg.kg-1 was given to infected mice for 24 h and 48 h, the inhibition rates of PGK were 60% (Male) and 48% (Female) as well as 75% (Male) and 62% (Female), respectively. Similar results were seen in PK activity. At 72 h after treatment the reduction rate of lactate content in Female worm was 72%, while that of Male was 48%. CONCLUSION: In the glycolytic pathway of both Male and Female schistosomes, PGK and PK activities were inhibited by Art. The GAPDH activity of Female worms was also susceptible to Art, While that of Male worms showed only temporary inhibition after treatment with Art. The Art reduced lactate content more in Female than in Male worms. (+info)
Preventive effect of artemether in rabbits infected with Schistosoma japonicum cercariae.
AIM: To study the effect of artemether (Art) for prevention of schistosomal infection. METHODS: Rabbits with single infection or reinfection with Schistosoma japonicum cercariae were treated intramuscularly (i.m.) or intragastrically (i.g.) with Art 5 -20 mg.kg-1 on d 7-15 after the first infection, followed by various regimens. RESULTS: When rabbits were injected i.m. Art 7.5 mg.kg-1 (i.e., one half of the effective dose given i.g. on d 7) followed by once every week for twice, the female worm reduction rate was only 42%. In infected rabbits treated i.g. with Art 10-20 mg.kg-1 given in the same administration schedule, the female worm reduction rates were > 91%. When Art 15 mg.kg-1 was given to rabbits on d 7-14 and the following dose of the drug was given at intervals of 7-14 d, the female worm reduction rates were > 94%. In rabbits reinfected with cercariae, the female reduction rate of Art given i.g. once a week for 3 times since d 8 after the first infection was 96% which was similar to that given once a week twice since d 14 after the first infection. CONCLUSION: Art should be given i.g. on d 7-15 after infection, followed by repeated dosing once every 7-15 d for a total of 3 doses. Art given i.g. daily for 2 consecutive days or given at 1-wk intervals since 7-15 d after infection also showed preventive effect. (+info)
Hepatosplenic morbidity in schistosomiasis japonica: evaluation with Doppler sonography.
In Southeast Asia, schistosomiasis japonica is an important cause of hepatic fibrosis and gastrointestinal hemorrhage. Reliable methods to investigate portal hypertension (PHT) clinically and epidemiologically on community level are lacking. Doppler sonography is an established tool for investigating PHT in hospital settings. In Leyte, The Philippines, 137 individuals underwent color Doppler sonography, stool examination, and serology for hepatitis B and C, liver cell injury and cholestasis. A total of 85% of the study population had been infected with Schistosoma japonicum. Sonographically, periportal liver fibrosis was seen in 25% and reticular echogenicities (network pattern) in 44%. Portal blood flow was decreased or portosystemic collaterals were present in 10% (adults throughout) and correlated with periportal fibrosis, but not with network lesions. Chronic viral hepatitis was rare. Thus, hepatic lesions are frequent in adults but not in children in areas endemic for S. japonicum. Periportal liver fibrosis indicates a risk of PHT, and network pattern fibrosis apparently does not. Doppler sonography is suitable for research under tropical field conditions. (+info)