OBJECTIVE: To investigate the effect of atovaquone on the cell cycle and apoptosis of non-Hodgkin's lymphoma Raji cells, and clarify the related mechanisms. METHODS: MTT assay and trypan blue dye exclusion method were used to evaluate the effect of atovaquone on the proliferation of Raji cells. After the cells were stained by PI staining, the cell cycle distribution was detected by flow cytometry. Cell apoptosis was analyzed by Annexin V/PI double binding assay. The intracellular alterations of reactive oxygen species were detected by 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The protein expression of cell cycle and apoptosis related molecules were detected by Western blot. RESULTS: Various concentrations of atovaquone (5-40 μmol/L) inhibited the growth of Raji cells in a concentration-dependent manner (r=0.951). The proliferation of Raji cells was significantly inhibited after treated by atovaquone (20 and 30 μmol/L) for 24, 48 and 72 h, which showed statistically different with that in the control group (P<0.01, P<0.001, P<0.001). G₁ phase arrest (P<0.01, P<0.001) and apoptosis (P<0.01) of Raji cells was induced by atovaquone (20 and 30 μmol/L) significantly for 24 h and 48 h, respectively. The expression of p-JAK2 and p-STAT3(Y705) protein were down-regulated significantly induced by atovaquone (P<0.001, P<0.05). Furthermore, atovaquone treatment could induce the decreasing of antiapoptotic protein Mcl-1, Bcl-2, and Bcl-xl expression level (P<0.05) and increasing of cleaved caspase-3 protein expression level. In addition, atovaquone could also induce the down-regulation of c-Myc (P<0.001, P<0.01) and cell cycle related molecules Cyclin D1, CDK4, and CDK6 (P<0.01, P<0.05) protein expression. CONCLUSION Atovaquone effectively inhibits cell proliferation and induces cell cycle arrest and apoptosis by suppression of STAT3 signaling pathway in Raji cells. It can be a potential therapeutic agent against non-Hodgkin's lymphoma.
Humans ; Atovaquone/pharmacology* ; Cell Cycle Checkpoints ; Apoptosis ; Lymphoma, Non-Hodgkin

BACKGROUND: Recently, many Korean people travel abroad where malaria is prevalent. However, in Korea, relatively little is known about compliance of chemoprophylaxis against malaria. This study was performed to determine the factors influencing compliance of chemoprophylaxis against malaria in Korean travelers. MATERIALS AND METHODS: Face to face interview, telephone interview and e-mail correspondence were performed to 241 people who were prescribed with atovaquone-proguanil at the international travelers' clinic of National Medical Center between February 2007 and October 2007. RESULTS: Total of 55 people out of 235 reported one or more events of adverse reactions after chemoprophylaxis (total 76 events). However, in 38 adverse events the link between chemoprophylaxis and adverse events were very weak. Compliance of malaria chemoprophylaxis with atovaquone-proguanil was 53.9% in the study group. The predictive factors for non-compliance were package tour, travel of business affair and young age group. Conclusions: Compliance of malaria chemoprophylaxis in Korea travelers was low compared with Dutch and French studies. More efforts to increase compliance are needed, especially in travelers on package tour, business travel and people under age 40.
Aluminum Hydroxide ; Atovaquone ; Carbonates ; Chemoprevention ; Commerce ; Compliance ; Drug Combinations ; Electronic Mail ; Humans ; Interviews as Topic ; Korea ; Malaria ; Proguanil

BACKGROUND: Recently, many Korean people travel abroad where malaria is prevalent. However, in Korea, relatively little is known about compliance of chemoprophylaxis against malaria. This study was performed to determine the factors influencing compliance of chemoprophylaxis against malaria in Korean travelers. MATERIALS AND METHODS: Face to face interview, telephone interview and e-mail correspondence were performed to 241 people who were prescribed with atovaquone-proguanil at the international travelers' clinic of National Medical Center between February 2007 and October 2007. RESULTS: Total of 55 people out of 235 reported one or more events of adverse reactions after chemoprophylaxis (total 76 events). However, in 38 adverse events the link between chemoprophylaxis and adverse events were very weak. Compliance of malaria chemoprophylaxis with atovaquone-proguanil was 53.9% in the study group. The predictive factors for non-compliance were package tour, travel of business affair and young age group. Conclusions: Compliance of malaria chemoprophylaxis in Korea travelers was low compared with Dutch and French studies. More efforts to increase compliance are needed, especially in travelers on package tour, business travel and people under age 40.
Aluminum Hydroxide ; Atovaquone ; Carbonates ; Chemoprevention ; Commerce ; Compliance ; Drug Combinations ; Electronic Mail ; Humans ; Interviews as Topic ; Korea ; Malaria ; Proguanil

Human babesiosis is a tick-borne infectious disease caused by Babesia species. The clinical diagnosis is difficult because of nonspecific symptoms like flu. Rapid diagnosis of human babesiosis is microscopic examination in peripheral blood smear (Giemsa-stain) which reveals characteristic forms of an intracellular quadruplet parasite. But differentiation between Babesia microti and Plasmodium species can be quite difficult because of the morphologic similarity. We experienced a case of human babesiosis. The patient was a 62-year old Korean male who had been in New Jersey, U.S.A for 2 months. We initially diagnosed as malaria infection because the peripheral blood smear revealed intracellular single ring form organism. But the patient was not improved significantly by the treatment with chloroquine regimen. Finally we confirmed human babesiosis by polymerase chain reaction for Babesia microti. We treated the patient successfully with a regimen of atovaquone and azithromycin which has fewer adverse reactions than a regimen of clindamycin and quinine.
Animals ; Atovaquone* ; Azithromycin* ; Babesia ; Babesia microti ; Babesiosis* ; Chloroquine ; Clindamycin ; Communicable Diseases ; Diagnosis ; Humans* ; Malaria ; Male ; Middle Aged ; New Jersey ; Parasites ; Plasmodium ; Polymerase Chain Reaction* ; Quadruplets ; Quinine

Human babesiosis is a tick-borne infectious disease caused by Babesia species. The clinical diagnosis is difficult because of nonspecific symptoms like flu. Rapid diagnosis of human babesiosis is microscopic examination in peripheral blood smear (Giemsa-stain) which reveals characteristic forms of an intracellular quadruplet parasite. But differentiation between Babesia microti and Plasmodium species can be quite difficult because of the morphologic similarity. We experienced a case of human babesiosis. The patient was a 62-year old Korean male who had been in New Jersey, U.S.A for 2 months. We initially diagnosed as malaria infection because the peripheral blood smear revealed intracellular single ring form organism. But the patient was not improved significantly by the treatment with chloroquine regimen. Finally we confirmed human babesiosis by polymerase chain reaction for Babesia microti. We treated the patient successfully with a regimen of atovaquone and azithromycin which has fewer adverse reactions than a regimen of clindamycin and quinine.
Animals ; Atovaquone* ; Azithromycin* ; Babesia ; Babesia microti ; Babesiosis* ; Chloroquine ; Clindamycin ; Communicable Diseases ; Diagnosis ; Humans* ; Malaria ; Male ; Middle Aged ; New Jersey ; Parasites ; Plasmodium ; Polymerase Chain Reaction* ; Quadruplets ; Quinine

While imported falciparum malaria has been increasingly reported in recent years in Korea, clinicians have difficulties in making a clinical diagnosis as well as in having accessibility to effective anti-malarial agents. Here we describe an unusual case of imported falciparum malaria with severe hemolytic anemia lasting over 2 weeks, clinically mimicking a coinfection with babesiosis. A 48-year old Korean man was diagnosed with severe falciparum malaria in France after traveling to the Republic of Benin, West Africa. He received a 1-day course of intravenous artesunate and a 7-day course of Malarone (atovaquone/proguanil) with supportive hemodialysis. Coming back to Korea 5 days after discharge, he was readmitted due to recurrent fever, and further treated with Malarone for 3 days. Both the peripheral blood smears and PCR test were positive for Plasmodium falciparum. However, he had prolonged severe hemolytic anemia (Hb 5.6 g/dl). Therefore, 10 days after the hospitalization, Babesia was considered to be potentially coinfected. A 7-day course of Malarone and azithromycin was empirically started. He became afebrile within 3 days of this babesiosis treatment, and hemolytic anemia profiles began to improve at the completion of the treatment. He has remained stable since his discharge. Unexpectedly, the PCR assays failed to detect DNA of Babesia spp. from blood. In addition, during the retrospective review of the case, the artesunate-induced delayed hemolytic anemia was considered as an alternative cause of the unexplained hemolytic anemia.
Anemia, Hemolytic/chemically induced/*etiology/*pathology ; Anti-Bacterial Agents/therapeutic use ; Antimalarials/therapeutic use ; Artemisinins/adverse effects/therapeutic use ; Atovaquone/therapeutic use ; Azithromycin/therapeutic use ; Babesiosis/complications/*diagnosis/drug therapy/*pathology ; Benin ; Blood/parasitology ; Coinfection/diagnosis/pathology ; Drug Combinations ; France ; Humans ; Korea ; Malaria, Falciparum/complications/*diagnosis/drug therapy/*pathology ; Male ; Middle Aged ; Plasmodium falciparum/*isolation & purification ; Proguanil/therapeutic use ; Travel ; Treatment Outcome