The effects of nitroquine on the ultrastructures of nitraery-throcytic stage of Plasmodium yoelii in mice / 第三军医大学学报

After a single oral dosed mg/kg) of nitroquine to the mice infected with Plasmodium yoelii,the morphological changes of the parasites were studied with optical and electron microscopy.Enlarged nucleus and some red granules scattered over the cytoplasm in the late trophozoites were observed under optical microscope,which may correspond to the autophagocytic vacuo-les or membranous residual bodies seen under electron microscope.Thirty minutes after the drug administration,the number of mitochondria with matrix cavitation was increased,the endoplasmic reticulum dilated,and ribosomes separated,detached,or disaggregated.Then the pelliculous complex and nuclear membrane of the parasites proliferated to form multi-layered structure with spiral curv?s or myelin sheath-like structure in the cytoplasm.The nuclear membrane was swollen and proliferated and the perinuclear cisterna was widened.In the late stage of drug action,the structure of the parasites was broken down to form a large number of autophagocytes.The findings indicate that nitroquine interferes with the structure and function of the cell membrane,cytoplasm and nucleus of malaria parasites and exerts its anti-malarial effects from many aspects.

The role of platelet-activating factor in liver injury / 中国药理学通报

Increasing hepatic vascular resistance and glycogenolysis are two principal effects induced by platelet-activating factor (PAF) in the liver. In addition, PAF is closely related with hepatic injury of ischemia-reperfusion and endotoxin. The progress is reviewed.

Study on Toxicity of Nitroquine-Dapson Compound & Its Treatment with Folic Acid or Folinic Acid in Mice and Dogs / 第三军医大学学报

The toxic effects of nitroquine-dapson compound(NQD) per os in mice and dogs were studied. The therapeutic index of NQD in mice(1911) is the highest among the six antimalarial preparations studied. The toxic effects(50mg/kg/ day for 3 successive days per os) in dogs were similar to those of nitroquine. They manifested themselves as the injury on the adrenal cortex and on the intestinal epithelium. When folic acid (4 mg/kg/day for 4 successive days) or folinic acid(0.3 mg/kg/day for 4 successive days) was administered intramuscularly to the toxicated animals, both the death rate and the incidence of diarrhea were greatly reduced. Pathological study confirmed that the injury on the intestinal epithelium was much milder and the goblet cell was much more numerous in the treated than in the untreated. The results suggest that folic acid or folinic acid can protect the less differentiated cells in the intestinal crypts, so that the clinical manifestations of NQD toxicity are reduced after treatment.

Effect of Nitroquine on Folate Metabolism of Mice Plasmodia / 第三军医大学学报

In order to locate the level of nitroquine action on the folate metabolism, ni-troquine was given to the mice infected with P. berghei or P. yoelii. To the first group of mice, different doses of nitroquine were given to its five subgroups. The second group of mice received the same doses of nitroquine as the first group but calcium leucovorin (folinic acid) 6 mg/kg/day intramuscularly, folic acid 20 mg/kg/day intramuscularly, or PABA 20 mg/kg/day orally were given to different subgroups respectively at the same time. It was found that the dose-effective curve of nitroquine was shifted to the right when PABA was administered simultaneously and the CD50 of nitroquine at that time was larger than that of nitroquine used singly. Both calcium leucovorin and folic acid essentially showed no antigonistic effects.From the antigonistic action of PABA against nitroquine) it is suggested that nitroquine is likely to achieve its antimalarial effect through its competition for dihydropteric acid synthetase with PABA. Other chains on the folic acid metabolism were also discussed.

Study on the Prophylactic Effect of Folic acid on the Toxicity of Nitroquine / 第三军医大学学报

232 mice were utilized in this study. ( 1 ) After administration of nitroquine 570mg/kg?1 po, the mice were given with normal saline(NS)and folic acid(NF,8 nag/kg x l im)in two subgroups respectively. 96h later, decrease in number and shorter in length of intestinal villi, and necrosis of epithelial cells, especially the crypt cells showed markedly in NS group, but much mild in NF group. ( 2 ) The DNA contents in the tissue of the small intestine showed decrease after nitroquine administration, & markedly in the larger dose and as the time going on. The values of cpm after the[3H] TdR incorporation into DNA wete much higher in NF group than in the NS group. The results suggest that the DNA synthesis in small intestine is promoted by folic acid, so that it is advantage for the repairing of damaged intestinal mucosa.