Segmented filamentous bacteria (SFBs) are apathogenic autochthonous bacteria in the murine small intestine that preferentially attach to Peyer's patch epithelium. SFBs have never been cultured in vitro. We have studied the effects of SFBs on the immune system of the host. Mice monoassociated with SFBs were compared with germ-free mice and with mice without SFBs but with a specific-pathogen-free (SPF) gut flora. SFBs versus no microbial flora raised the number of lymphoid cells in the lamina propria of the ileal and cecal mucosa, raised the number of immunoglobulin A (IgA)-secreting cells in the intestinal mucosa, produced elevated IgA titers in serum and intestinal secretions, and enhanced the concanavalin A-induced proliferative responses of mesenteric lymph node cells. The SPF flora had effects similar to but less pronounced than those mediated by SFBs. The results indicate that SFBs stimulate the mucosal immune system to a greater extent than do other autochthonous gut bacteria.

Naphthylisoquinoline alkaloid-containing extracts from species of the families Dioncophyllaceae and Ancistrocladaceae and purified alkaloids derived therefrom were shown to exhibit antiparasitic activity in Plasmodium berghei-infected mice. Several extracts and alkaloids, especially dioncophylline C and dioncopeltine A, isolated from Triphyophyllum peltatum (Dioncophyllaceae), displayed high levels of activity. Dioncopeltine A was able to suppress parasitemia almost totally, while dioncophylline C cured infected mice completely after oral treatment with 50 mg kg of body weight(-1) day(-1) for 4 days without noticeable toxic effects. Analysis of the dose-response relationship of dioncophylline C revealed a 50% effective dosage (ED50) of 10.71 mg kg(-1) day(-1) under these conditions. Although four daily treatments with 50 mg kg(-1) day(-1) are needed to achieve radical cure, one oral dose is sufficient to kill 99.6% of the parasites. Intravenous application of dioncophylline C is even more effective, with an ED50 of 1.90 mg kg(-1) day(-1) and no noticeable toxic effects. The compound also suppressed more established P. berghei infections when orally applied at day 3 after infection. Both dioncopeltine A and dioncophylline C are active against the chloroquine-resistant P. berghei Anka CRS parasites. Sustained release of these compounds at 20 mg kg(-1) day(-1) by implanted miniosmotic pumps exhibited curative effects. The naphthylisoquinoline alkaloids are therefore promising new antimalarial agents.

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In this study, the advantage of the use of chloroquine (CQ) containing liposomes (lipCQ) over free CQ in the chemotherapy of murine malaria (Plasmodium berghei) was demonstrated. The maximum permissible dose per intraperitoneal injection was 0.8 and 10 mg for CQ and lipCQ, respectively. An increase in therapeutic and prophylactic efficacy of lipCQ in comparison with free CQ at a 0.8 mg CQ dose level was found. It was possible to obtain 100% efficacy (injection at day 5 after infection; parasitaemia 4-8%) with one single intraperitoneal injection of 6 mg lipCQ. Moreover, the ability to increase the doses of CQ per injection after liposome encapsulation allowed successful treatment of infections with CQ-resistant Plasmodium berghei which could not be cured by a 7-day course with the maximum tolerable dose of free CQ of 0.8 mg/mouse/day.