• Journal of Korean Neurosurgical Society
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• 제38권1호
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• pp.47-53
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• 2005

Objective : Anti-malaria drugs may modulate tumor resistance to chemotherapeutic agents, but it has not been proven effective in the treatment of malignant gliomas. The aim of this study was to determine whether adequate pre-clinical data on co-administration of chemotherapeutic agents with anti-malaria drugs on malignant cell lines could be obtained that would warrant its further potential consideration for use in a clinical trial for malignant gliomas. Methods : Two malignant glioma cell lines [U87MG, T98G] were treated with chemotherapeutic agents alone or with anti-malaria drugs. Cells were incubated with drugs for 4 days. Following the 4-day incubation, drug sensitivity assays were performed using 3-[4,5-dimethyl-2-thiazol-2-yl] 2,5-diphenyltetrazolium bromide [MTT] assay following optimization of experimental conditions for each cell lines and cell viability was calculated. Results : In all of four chemotherapeutic agents[doxorubicin. vincrisitne, nimustine, and cisplatin], the cell viability was found to be markedly decreased when hydroxychloroquine was co-administered on both U87MG and T98G cell lines. The two way analysis of variance[ANOVA] yielded a statistically significant two-sided p-value of 0.0033[doxorubicin], 0.0005[vincrisitne], 0.0007[nimustine], and 0.0003[cisplatin] on U87MG cell lines and 0.0006[doxorubicin], 0.0421[vincrisitne], 0.0317[nimustine], and 0.0001[cisplatin] on T98G cell lines, respectively. However, treatment with chloroquine and primaquine did not induce a decrease in cell viability on both U87MG and T98G cell lines. Conclusion : Our data support further consideration of the use of hydroxychloroquine prior to systemic chemotherapy to maximize its tumoricidal effect for patients with malignant gliomas.

• Parasites, Hosts and Diseases
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• 제59권5호
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• pp.447-455
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• 2021

Vivax malaria incidence in Korea is now decreased and showing a low plateau. Nowadays, vivax malaria in Korea is expected to be successfully eliminated with anti-malaria chemotherapy, primaquine, and vector control. The glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with potential hemolytic anemia after primaquine administration. This inborn disorder has a pivotal polymorphism with genetic variants and is the most prevalent X-chromosome-linked disorder. The prevalence of G6PD deficiency was previously reported negligible in Korea. As the population of multicultural families pertaining marriage immigrants and their adolescents increases, it is necessary to check G6PD deficiency for them prior to primaquine treatment for vivax malaria. The prevalence of G6PD variants and G6PD deficiency in multicultural families was performed in 7 counties and 2 cities of Jeollanam-do (Province), Gyeonggi-do, and Gangwon-do. A total of 733 blood samples of multicultural family participants were subjected to test the phenotypic and genetic G6PD deficiency status using G6PD enzyme activity quantitation kit and PCR-based G6PD genotyping kit. The G6PD phenotypic deficiency was observed in 7.8% of male adolescent participants and 3.2% of materfamilias population. Based on the PCR-based genotyping, we observed total 35 participants carrying the mutated alleles. It is proposed that primaquine prescription should seriously be considered prior to malaria treatment.

• Parasites, Hosts and Diseases
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• 제47권4호
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• pp.421-424
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• 2009

Malaria parasites adapt to the oxidative stress during their erythrocytic stages with the help of vital thioredoxin redox system and glutathione redox system. Glutathione reductase and thioredoxin reductase are important enzymes of these redox systems that help parasites to maintain an adequate intracellular redox environment. In the present study, activities of glutathione reductase and thioredoxin reductase were investigated in normal and Plasmodium berghei-infected mice red blood cells and their fractions. Activities of glutathione reductase and thioredoxin reductase in P. berghei-infected host erythrocytes were found to be higher than those in normal host cells. These enzymes were mainly confined to the cytosolic part of cell-free P. berghei. Full characterization and understanding of these enzymes may promise advances in chemotherapy of malaria.

• Parasites, Hosts and Diseases
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• 제40권1호
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• pp.1-7
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• 2002

The purpose of treatment for uncomplicated malaria is to produce a radical cute using the combination of: artesunate (4 mg/kg/day) plus mefloquine (8 mg/kg/day) for 3 days; a fixed dose of artemether and lumefantrine (20/120 mg tablet) named $Coartem^{\circledR}$ (4 tablets twice a day for three days for adults weighing more than 35 kg); quinine 10 mg/kg 8-hourly plus tetracycline 250 mg 6-hourly for 7 days (or doxycycline 200 mg as an alternative to tetracycline once a day for 7 days) in patients aged 8 years and over; $Malarone^{\circledR}$ (in adult 4 tablets daily for 3 days). In treating severe malaria, early diagnosis and treatment with a potent antimalarial drug is recommended to save the patient's life. The antimalarial drugs of choice are: intravenous quinine or a parenteral form of an artemisinin derivative (artesunate i.v./i.m. for 2.4 mg/kg followed by 1.2 mg/kg injection at 12 and 24 hr and then daily for 5 days; artemether i.m. 3.2 mg/kg injection followed by 1.6 mg/kg at 12 and 24 hrs and then dialy for 5 days; arteether i. m. ($Artemotil^{\circledR}$) with the same dose of artemether or artesunate suppository (5 mg/kg) given rectally 12 hourly for 3 days. Oral arlemisinin derivatives (artesunate, artemether, and dihydroartemisinin with 4 mg/kg/day) could replace parenteral forms when patients can tolerate oral medication. Oral mefloquine (25 mg/kg divided into two doses 8 hrs apart) should be given at the end of the artemisinin treatment course to reduce recrudescence.

• Parasites, Hosts and Diseases
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• 제54권4호
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• pp.415-421
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• 2016

The drug-resistance of malaria parasites is the main problem in the disease control. The huge Brazilian biodiversity promotes the search for new compounds, where the animal kingdom is proving to be a promising source of bioactive compounds. The main objective of this study was to evaluate the antiplasmodial and cytotoxic activity of the compounds obtained from the toad venoms of Brazilian Amazon. Toad venoms were collected from the secretion of Rhinella marina and Rhaebo guttatus in Mato Grosso State, Brazil. The powder was extracted at room temperature, yielding 2 extracts (RG and RM) and a substance ('1') identified as a bufadienolide, named telocinobufagin. Growth inhibition, intraerythrocytic development, and parasite morphology were evaluated in culture by microscopic observations of Giemsa-stained thin blood films. Cytotoxicity was determined against HepG2 and BGM cells by MTT and neutral red assays. The 2 extracts and the pure substance ('1') tested were active against chloroquine-resistant Plasmodium falciparum strain, demonstrating lower $IC_{50}$ values. In cytotoxic tests, the 2 extracts and substance '1' showed pronounced lethal effects on chloroquine-resistant P. faciparum strain and low cytotoxic effect, highlighting toad parotoid gland secretions as a promising source of novel lead antiplasmodial compounds.

• Parasites, Hosts and Diseases
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• 제60권1호
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• pp.39-43
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• 2022

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.