Background: In the Philippines, malaria morbidity and mortality have decreased since the 1990s by effective malaria control. Several epidemiological surveys have been performed in the country, but the characteristics of the Plasmodium falciparum populations are not yet fully understood. In this study, the genetic structure of P. falciparum populations in the Philippines was examined.

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Abstract. Previous intervention studies have shown that the most effective agents used in the treatment of malaria were isolated from natural sources. Plants consumed by non-human primates serve as potential drug sources for human disease management due to the similarities in anatomy, physiology and disease characteristics. The present study investigated the antiplasmodial properties of the primate-consumed plant, Schima wallichii (S. wallichii) Korth. (family Theaceae), which has already been reported to have several biological activities. The ethanol extract of S. wallichii was fractionated based on polarity using n-hexane, ethyl acetate and water. The antiplasmodial activity was tested in vitro against chloroquine-resistant Plasmodium falciparum (P. falciparum) at 100 µg/ml for 72 h. The major compound of the most active ethyl acetate fraction was subsequently isolated using column chromatography and identified by nuclear magnetic resonance. The characterized compound was also tested against chloroquine-resistant P. falciparum in culture to evaluate its antiplasmodial activity. The ethanol extract of S. wallichii at 100 µg/ml exhibited a significant parasite shrinkage after 24 h of treatment. The ethyl acetate fraction at 100 µg/ml was the most active fraction against chloroquine-resistant P. falciparum. Based on the structural characterization, the major compound isolated from the ethyl acetate fraction was kaempferol-3-O-rhamnoside, which showed promising antiplasmodial activity against chloroquine-resistant P. falciparum with an IC 50 of 106 µM after 24 h of treatment. The present study has provided a basis for the further investigation of kaempferol-3-O-rhamnoside as an active compound for potential antimalarial therapeutics.

VAMP7 or tetanus neurotoxin-insensitive vesicleassociated membrane protein (TI-VAMP) has been proposed to regulate apical transport in polarized epithelial cells, axonal transport in neurons and lysosomal exocytosis. To investigate the function of VAMP7 in vivo, we generated VAMP7 knockout mice. Here, we show that VAMP7 knockout mice are indistinguishable from control mice and display a similar localization of apical proteins in the kidney and small intestine and a similar localization of axonal proteins in the nervous system. Neurite outgrowth of cultured mutant hippocampal neurons was reduced in mutant neurons. However, lysosomal exocytosis was not affected in mutant fibroblasts. Our results show that VAMP7 is required in neurons to extend axons to the full extent. However, VAMP7 does not seem to be required for epithelial cell polarity and lysosomal exocytosis.

H uman cerebral malaria is caused by excessive adherence of Plasmodium falciparum-infected erythrocytes (pRBCs) to the microvasculature of several organs, including the brain. pRBCs containing mature parasites adhere to endothelial cells (EC) lining the lumens of postcapillary vessels, and this phenomenon is known as sequestration. After sequestration, cerebral malaria develops through a complex process involving multiple events, including obstruction of the microvasculature by pRBCs (1, 2). Several host receptors, including CD36, intercellular adhesion molecule 1 (ICAM-1), chondroitin sulfate A (CSA), platelet͞endothelial cell adhesion molecule 1 (PECAM-1/CD31), vascular cell adhesion molecule 1 (VCAM-1), thrombospondin, and E-selectin, have been identified on EC as potential mediators for cytoadherence of pRBCs (3-8). Host and parasite factors are thought to participate in the pathogenesis of severe malaria, in which symptoms of cerebral malaria are the most fulminant. However, the mechanism underlying the cytoadherence of pRBCs in the pathology of severe malaria is not completely understood. It has been suggested by several investigators that other unidentified receptors that mediate the adherence of pRBCs to EC may be present (9-11).Fractalkine͞CX 3 CL1 (FKN) is a recently identified chemokine with a unique structure. The molecule possesses a single CXXXC CD at the N terminus, which precedes 17 mucin-like repeats (the central stalk region) and the transmembrane segment at the C terminus. FKN is expressed as a membrane-bound form on EC activated by proinflammatory cytokines such as tumor necrosis factor ␣, IFN-␥, and IL-1␤ (12, 13). FKN is constitutively expressed on cells in a variety of nonhematopoietic tissues, including the brain, heart, kidneys, and lungs (12). The membrane-bound form of FKN on EC mediates adherence of blood mononuclear cells with the FKN receptor (CX 3 CR-1) (14, 15). At the same time, the soluble form promotes chemotaxis of these cells to sites of acute inflammation (12, 13). Because the key cytokine produced during malaria infection induces expression of FKN on EC at sites of sequestration, it is possible that FKN contributes to disease manifestations in patients with severe malaria.Here we report that the membrane-bound form of FKN on EC can mediate cytoadherence of pRBCs.Materials and Methods P. falciparum Culture. P. falciparum was cultured in vitro as described (16). The 21 clinical isolates of P. falciparum used in this study were obtained from uncomplicated, complicated, and cerebral malaria patients at the hospital of the International Medical Center of Japan (Tokyo), Tokyo Metropolitan Komagome Hospital, and Davao Regional Hospital (Davao, The Philippines). Informed consent was obtained from each patient before the blood sampling. Peripheral blood was collected into tubes coated with EDTA and centrifuged at 1,500 rpm for 5 min at room temperature to remove the plasma. The packed cells were washed three times with RPMI 1640 (Ϫ) (RPMI medium 1640 supplemented with 24 mM NaHCO 3 ...

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One of the most characteristic clinical features in cutaneous leishmaniasis is the development of nodules followed by ulcerations at the site of infection. Leishmania amazonensis-infected mice show similar ulcerative lesions. Leishmania-infected severe combined immunodeficiency (SCID) mice, however, have been shown to develop nonulcerative nodules. In the present study, the roles of T cells in ulceration were examined using SCID mice in cell reconstitution experiments. After development of nonulcerative nodules, SCID mice were inoculated with splenocytes from either Leishmania-infected or naive immunocompetent mice, resulting in ulceration in all mice. When naive splenocytes were depleted of CD4 ؉ , CD8 ؉ , or B220 ؉ cell populations and the remaining cells were injected into Leishmania-infected SCID mice after the development of nodules, only SCID mice inoculated with splenocytes depleted of CD4 ؉ cells did not show ulceration. The evidence obtained in this study clearly shows that the CD4 ؉ cell population is indispensable for ulceration in leishmaniasis lesions of SCID mice.