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Nishi-Tokyo-shi, Japan

Kimura M.,Shin yamanote Hospital | Koga M.,Tokyo Medical University | Kikuchi T.,Tokyo Medical University | Miura T.,Tokyo Medical University | And 2 more authors.
Parasitology International

Malaria remains an important health risk among travelers to tropical/subtropical regions. However, in Japan, only 2 antimalarials are licensed for clinical use - oral quinine and mefloquine. The Research Group on Chemotherapy of Tropical Diseases introduced atovaquone-proguanil in 1999, and reported on its excellent antimalarial efficacy and safety for treating non-immune patients with uncomplicated Plasmodium falciparum malaria (20 adult and 3 pediatric cases) in 2006. In the present study, additional cases of malaria were analyzed to confirm the efficacy and safety of this antimalarial drug. Fourteen adult and 2 pediatric cases of P. falciparum malaria and 13 adult cases and 1 pediatric case of P. vivax/. ovale malaria were successfully treated with atovaquone-proguanil, including 3 P. falciparum cases in which the antecedent treatment failed. Two patients with P. vivax malaria were treated twice due to primaquine treatment failure as opposed to atovaquone-proguanil treatment failure. Except for 1 patient with P. falciparum malaria who developed a moderate liver function disturbance, no significant adverse effects were observed. Despite the intrinsic limitations of this study, which was not a formal clinical trial, the data showed that atovaquone-proguanil was an effective and well-tolerated therapeutic option; licensure of this drug in Japan could greatly contribute to individually appropriate treatment options. © 2012 Elsevier Ireland Ltd. Source

Namikawa K.,Sapporo Medical University | Ouchi K.,Kawasaki Medical School | Kimura M.,Shin yamanote Hospital
Journal of Travel Medicine

Background. There is concern that Japanese travelers are poorly protected against travel-associated infectious diseases including vaccine-preventable infections. This prompted us to study Japanese travelers for measures taken to reduce their risk of acquiring an infectious disease and their immunization uptake. Methods. During April 2007 to May 2008, a questionnaire study was conducted using the European Travel Health Advisory Board (ETHAB) protocol and targeting Japanese group tour clients as well as individual travelers to developing countries. Results. A total of 302 returned questionnaires were analyzed. While the majority (87.4%) sought general information on their destination, few (38.7%) sought the travel health information. Very few (2.0%) got the health information from travel medicine specialists. More than half were either unaware of the risks or thought there was no risk of hepatitis A, hepatitis B, and typhoid fever in their destination. Only half (50.7%) thought vaccines provided sufficient protection and very few (13.6%) believed that vaccines were safe. For most of the vaccine-preventable diseases, only fewer than 10% had received the vaccines. Conclusions. There is a need for specialized travel health services in Japan and health professionals should be encouraged to expand these services. Japanese travelers should be made aware of the importance of seeking pre-travel health advice and information on the health risks at their destination. Travel health professionals should provide a balanced view of the risks and benefits of immunization, and misperceptions about immunization should be addressed. © 2010 International Society of Travel Medicine. Source

Kinoshita A.,Himeji Dokkyo University | Yamada H.,International University of Health and Welfare | Kotaki H.,International University of Health and Welfare | Kimura M.,Shin yamanote Hospital
Malaria Journal

Background. Concern over the potential cardiotoxicity of anti-malarial drugs inducing a prolonged electrocardiographic QT interval has resulted in the almost complete withdrawal from the market of one anti-malarial drug - halofantrine. The effects on the QT interval of four anti-malarial drugs were examined, using the guinea pig heart. Methods. The guinea pig heart was isolated, mounted on a Langendorff apparatus, and was then perfused with pyruvate-added Klebs-Henseleit solutions containing graded concentrations of the four agents such as quinidine (0.15 - 1.2 M), quinine (0.3 - 2.4 M), halofantrine (0.1 - 2.0 M) and mefloquine (0.1 - 2.0 M). The heart rate-corrected QaTc intervals were measured to evaluate drug-induced QT prolongation effects. Results. Quinidine, quinine, and halofantrine prolonged the QaTc interval in a dose-dependent manner, whereas no such effect was found with mefloquine. The EC50values for the QaTc prolongation effects, the concentration that gives a half-maximum effect, were quinidine < quinine halofantrine. Conclusions. In this study, an isolated, perfused guinea pig heart system was constructed to assess the cardiotoxic potential of anti-malarial drugs. This isolated perfused guinea pig heart system could be used to test newly developed anti-malarial drugs for their inherent QT lengthening potential. More information is required on the potential variation in unbound drug concentrations in humans, and their role in cardiotoxicity. © 2010 Kinoshita et al; licensee BioMed Central Ltd. Source

Mori Y.,Jikei University School of Medicine | Taniguchi Y.,Shin yamanote Hospital | Matsuura K.,Jikei University School of Medicine | Sezaki K.,The Surgical Center | And 2 more authors.
Diabetes Technology and Therapeutics

Background: This study was performed to examine the efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes using continuous glucose monitoring (CGM) of 24-h glycemic changes. Subjects and Methods: The study was a prospective open-label pilot study in patients with type 2 diabetes who were admitted to our hospital and treated with sitagliptin alone or concomitantly with another oral hypoglycemic drug. CGM was performed for 2 days before sitagliptin administration and for another 2 days after administration. The average 24-h blood glucose level, SD of the 24-h blood glucose level, 24-h glycemic fluctuation range, mean amplitude of glycemic excursions (MAGE), and hyperglycemic and hypoglycemic time periods were compared before and after administration. Results: Sitagliptin administration alone and with a concomitant drug decreased the average 24-h blood glucose level, SD of the 24-h blood glucose level, 24-h glycemic fluctuation range, MAGE, and hyperglycemic time, compared with these parameters before administration. There were significant correlations between the average 24-h blood glucose level before administration and the decrease in the average 24-h blood glucose level after administration and between MAGE before administration and the decrease in MAGE after administration. Conclusions: Sitagliptin decreased the average glycemic level and also improved 24-h glycemic fluctuation, including postprandial hyperglycemia. © 2011, Mary Ann Liebert, Inc. Source

Furuta T.,Tokyo Medical University | Kimura M.,Shin yamanote Hospital | Watanabe N.,Jikei University School of Medicine
American Journal of Tropical Medicine and Hygiene

In cerebral malaria, the binding of parasitized erythrocytes to the cerebral endothelium and the consequent angiogenic dysregulation play a key role in pathogenesis. Because vascular endothelial growth factor (VEGF) is widely regarded as a potent stimulator of angiogenesis, edema, inflammation, and vascular remodeling, the plasma levels of VEGF and the soluble form of the VEGF receptor (sVEGFR)-1 and -2 in uncomplicated malaria patients and healthy adults were measured by enzyme-linked immunosorbent assay (ELISA) to examine their roles in malaria. The results showed that VEGF and sVEGFR-2 levels were significantly elevated in malaria patients compared with healthy adults. Moreover, it was confirmed that malarial parasite antigens induced VEGF secretion from the human mast cell lines HMC-1 or KU812 cell. This is the first report to suggest that the interaction of VEGF and sVEGFR-2 is involved in the host immune response to malarial infection and that malarial parasites induce VEGF secretion from human mast cells. © 2010 by The American Society of Tropical Medicine and Hygiene. Source

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