Targeting of aminopeptidase N to bile canaliculi correlates with secretory activities of the developing canalicular domain.

We have used human hepatoma cell lines as an in vitro model to study the development of hepatic bile canaliculi (BC). Well-differentiated hepatoma cells cultured for 72 hours could develop characteristic spheroid structures at sites of cell-cell contact that contained tight junctions and various membrane protein markers, resembling BC found in vivo. Intact cytoskeleton was essential for this differentiation process. In the coculture experiments in which cells of different origins were populated together, BC only formed between hepatic cells and preferentially among well-differentiated cells. Poorly differentiated hepatoma cells never formed BC among themselves, but could be induced to undergo canalicular differentiation by interacting with well-differentiated cells. During BC morphogenesis, integral canalicular membrane proteins were gradually delivered and accumulated at the developing BC. Among them, targeting of aminopeptidase N (APN) seemed to correlate with activation of certain secretory functions. Specifically, only APN-positive BC supported excretion of fluorescein diacetate (FDA) and 70-kd dextran, but had no relationship with secretion of horseradish peroxidase (HRP). Targeting of another BC protein, dipeptidyl peptidase IV (DPPIV), on the other hand, bore no association with any secretory activity examined. In addition, inhibition of enzymatic activity of APN could perturb canalicular differentiation without affecting cell proliferation. Our results suggest that targeting of APN proteins may reflect or even play an important role in the development and functional maturation of the canalicular structures.

Electron microscopic observations of tegumental damage in adult Schistosoma japonicum after in vivo treatment with levo-praziquantel.

The in vivo effects of a single dose of levo-praziquantel, 75 mg/kg in PEG 400, on the tegumental surface of adult S. japonicum were compared with the effects of a single dose (150 mg/kg) of the mixed isomer preparation, using scanning and transmission electron microscope. Worms were recovered from mice at 10 min, 30 min, 1 hr, 4 hr, 12 hr, 24 hr and 48 hr after treatment. After 10 min exposure to either compound, the tegumental folds and sensory organelles were swollen and the tegument vacuolated. After 12-24 hr, the surface was eroded and exfoliated with exposure of intrategumental and/or subtegumental tissues and attachment of leukocytes to the denuded areas. Vehicle controls were normal throughout the time period examined. These studies demonstrate that the levo isomer of praziquantel causes acute structural damage to the tegument similar to that seen with the mixed isomer preparation.

[Studies on the histochemistry of Culex tritaeniorhynchus larvae infected with Coelomomyces indica].

A sectional survey with histochemical technique was carried out on Culex tritaeniorhynchus larvae infected with Coelomomyces indica in comparison to the noninfected larvae. Studies were pursued by using micrograph and imaging analysis. The results showed that the glycogen, protein and nucleic acid (RNA and DNA) reaction in the infected group were less than those of the control group. The gray level assessment in tissue imaging showed marked difference between the two groups. It is suggested that C. indica has significant effect on the above biochemical elements of the mosquito larvae, which might be considered an important mechanism in the pathogenicity of the fungus.

Comparative efficacy of levo-praziquantel and praziquantel in treatment of schistosomiasis japonica at a single dose.

The result of a randomized double blind comparison of therapeutic efficacy of single doses of levo-praziquantel (L-PZQ) and praziquantel (PZQ) in the treatment of 139 matched pairs of proved cases of schistosomiasis japonica was reported, 268 were chronic early cases and 10 were late cases. The dosage of L-PQZ was 20 mg/kg, and that of PZQ was 40 mg/kg. Four and 6 months after treatment the stool-ova negative conversion rates were 94.8% and 96.3% for the L-PZQ group, and 97.1% and 94.0% for the PZQ group respectively (P greater than 0.05).

Comparison of the therapeutic efficacy and side effects of a single dose of levo-praziquantel with mixed isomer praziquantel in 278 cases of schistosomiasis japonica.

A randomized double-blind study comparing the therapeutic efficacy of single dose of levo-praziquantel and mixed isomer praziquantel was carried out on 139 matched pairs of patients with schistosomiasis japonica. A single dose of either levo-praziquantel (20 mg/kg) or praziquantel (40 mg/kg) was given to each patient. Four and six months after treatment, the stool ova negative conversion rates were 94.85% and 96.27% for the levo-praziquantel group, and 97.06% and 94.03% for the praziquantel group, respectively; there was no statistically significant difference between the two treatments (P greater than 0.05). For lightly and moderately infected patients, a single 20 mg/kg dose of levo-praziquantel was as efficacious as 40 mg/kg of praziquantel. Moreover, levo-praziquantel produced fewer side effects than praziquantel. These results suggest that levo-praziquantel is the component of the mixed isomer preparation that is antihelminthic. Levo-praziquantel could be used therapeutically at half the current dose of the mixed isomer drug.

[Histopathology of experimental hepatic amebiasis].

The method of intrahepatic inoculation was successfully used to establish an experimental model of hepatic amebiasis in golden hamsters for studying its pathological morphology. Three types of macroscopic liver lesions, i.e., isolated abscess, multinodular abscess and ruptured lesion were described. On light microscopy the alteration and the proliferation type lesions were found as distinct pathological characteristics of the early and advanced hepatic amebiasis respectively. The development pattern of hepatic amebiasis and the pathogenicity of Entamoeba histolytica were discussed.