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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Soluble antigens were prepared from Plasmodium falciparum and P. vivax and were evaluated in the indirect hemagglutination test. These antigens, attached to aldehyde-fixed type "O" erythrocytes, detected antibodies in more than 91% of infections with the homologous Plasmodium species. Detection rates in infections caused by the heterologous species ranged from 72% to 76%. Positive reactions occurred in less than 2% of sera from persons without malaria infection.
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PMID:The indirect hemagglutination test for malaria. Evaluation of antigens prepared from Plasmodium falciparum and Plasmodium vivax. 5 Jul 47

A new hemagglutination test for human malaria, done with Plasmodium gallinaceum-parasitized, aldehyde-fixed, chicken erythrocytes as a stable lyophilized reagent, is described. The test was positive in every human case of falciparum or vivax malaria in which there was parasitemia. It detected only IgM anti-plasmodial antibodies and usually became negative within a few weeks after treatment. As a practical and sensitive test for active malaria, the P. gallinaceum hemagglutination test should be complementary tool for seroepidemiological studies.
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PMID:Plasmodium gallinaceum-parasitized chicken erythrocytes in a practical hemagglutination test for IgM antibodies in human malaria. 38 Mar 70

Antigen was prepared from Plasmodium brasilianum harvested from an infected spider monkey. This antigen was attached to aldehyde-fixed, human type O cells, and was tested against sera from human cases of P. malaria, P. vivax, P. falciparum, and P. ovale infection, and sera from noninfected persons. At dilutions of 1:16 or greater the antigen failed to react in sera from noninfected persons. It reacted at titers of 16 or above with sera from 85% of the persons with P. malariae infection, 83% with P. vivax infection, 70% with P. falciparum infection, and 70% with P. ovale infection.
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PMID:Plasmodium brasilianum antigen for use in the indirect hemagglutination test. 125 94

Among other macrophage secretory products, H2O2 plays an important role in the host's defense against malaria (Wozencraft et al., Infect. Immun., 43, 664, (1984]. In our in vitro studies on the human malaria parasite Plasmodium falciparum, hydrogen peroxide was produced by the alcohol oxidase-catalyzed reaction ethanol + O2----acetaldehyde + H2O2 (EC 1.1.3.13). At concentrations of 8.7 mM (= 0.5%) ethanol and 0.1 U alcohol oxidase per ml culture, more than 95% of the parasites were irreversibly damaged. Acetaldehyde was found to be parasiticidal per se--probably by releasing immature forms of P. falciparum from erythrocytes--but CH3CHO concentrations as high as 90 mM were required for complete elimination of the parasites. Ethanol (less than 20 mM) or alcohol oxidase alone had no significant effect on parasite viability. As discussed, the ethanol/alcohol oxidase system might be of interest as a potential chemotherapeutic principle, especially since metabolism and pharmacology of the substrates and products are well understood.
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PMID:Antimalarial activity of the ethanol/alcohol oxidase system in vitro. 218 76

Plasmodium falciparum was shown to synthesize pteroylpolyglutamate de novo from guanosine 5'-triphosphate (GTP), p-aminobenzoate (PABA), and L-glutamate (L-Glu). The parasite also had the capacity to synthesize pteroylpolyglutamate from both intact and degradation moieties (p-aminobenzoylglutamate and pterin-aldehyde) of exogenous folate added into the growth medium. The major product was identified as 5-methyl-tetrahydroteroylpentaglutamate following exposure to pteroylpolyglutamate hydrolase and oxidative degradation of the C9-N10 bond in the molecule and identification of products by reversed-phase high performance liquid chromatography. Inhibition of pteroylpentaglutamate synthesis from the radiolabelled metabolic precursors (GTP, PABA, L-Glu) and folate by the antifolate antimalarials, pyrimethamine and sulfadoxine at therapeutic concentrations, may suggest the existence of a unique biosynthetic pathway in the malaria parasite.
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PMID:De novo and salvage biosynthesis of pteroylpentaglutamates in the human malaria parasite, Plasmodium falciparum. 264 36

In the district of Sahibganj, Bihar, India, there were 23,670 new cases of kala-azar between 1985 and 1990. The Social Development Centre, Dumka, drafted an emergency plan as a solution. 30 village health workers attended a 3-day training course regarding how to administer sodium stibogluconate intramuscularly, spray DDT, conduct door-to-door surveys, and refer affected persons to health centers. Kala-azar awareness programs in the villages imparted information on the treatment and control of the disease explaining that the disease could not be controlled by witch-doctors. DDT was sprayed during January/February and May/June on the inner walls of houses and covered cowsheds in order to eradicate sandfly prevalence. Persons who had had fever for more than 3 weeks underwent examinations for total and differential counts of white blood cells, haemoglobin concentration, aldehyde test, and thick and thin blood smears for the detection of malaria parasites. Treatment consisted of sodium stibogluconate given intramuscularly at 20 mg per kg body weight daily for 20 days in new cases and for 40 days in relapsed patients, with a maximum of 850 mg. Clinical cure was achieved if patients became afebrile and their spleens returned to normal size. If no relapse occurred in 6 months, the patients were regarded as definitively cured. Of the 1640 treated patients, 1592 were cured, and of the 48 patients who relapsed and were treated again with a 40-day course of sodium stibogluconate, 8 relapsed a second time. 44 patients became unresponsive to sodium stibogluconate and were sent to hospitals for treatment. The spraying performed by the village health workers reduced the incidence of kala-azar and malaria in 3 villages, while increased numbers of cases were recorded in 1 village. Remote tribal areas need educative, preventive, and curative programs backed up by mobile hospitals carrying diagnostic and spraying equipment.
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PMID:A kala-azar control programme for remote tribal communities. 794 51

Gangliosides are known to be suitable targets for immune attack against cancer but they are poorly immunogenic. Active immunization with ganglioside/BCG or liposome vaccines results in moderate titer IgM antibody responses of short duration. Covalent attachment of poorly immunogenic antigens to immunogenic proteins is a potent method for inducing an IgG antibody response. GD3, a dominant ganglioside on malignant melanoma, was modified by ozone cleavage of the double bond in the ceramide backbone, an aldehyde group introduced and used for coupling via reductive amination to epsilon-amino-lysyl groups of proteins. Utilizing this method, GD3 conjugates were constructed with: 1. Synthetic multiple antigenic peptide (MAP) constructs expressing 4 repeats of a malaria T-cell epitope; 2. Outer membrane proteins (OMP) of Neisseria meningitidis; 3. Cationized bovine serum albumin; 4. Keyhole limpet hemocyanin (KLH); and 5. Polylysine. In addition, conjugates containing only the GD3 oligosaccharide were synthesized. All constructs were tested for antigenicity using anti-GD3 antibody R24, and for immunogenicity in mice. Serum antibody levels were analyzed by ELISA and immune thin-layer chromatography. Results in the mouse show a significant improvement in the IgM antibody response and a consistent IgG response against GD3 using GD3-KLH conjugates. Other carrier proteins and the use of GD3 oligosaccharide were significantly less effective. If improved immunogenicity and clinical benefit with conjugate vaccines can be demonstrated in patients with melanoma, this approach may be applicable to patients with other tumors of neuroectodermal origin, including gliomas, glioblastomas, astrocytomas, and neuroblastomas.
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PMID:Ganglioside conjugate vaccines. Immunotherapy against tumors of neuroectodermal origin. 808 40

The inhibition of cysteine proteases is being studied as a strategy to combat parasitic diseases such as Chagas' disease, leishmaniasis, and malaria. Cruzain is the major cysteine protease of Trypanosoma cruzi, the etiologic agent of Chagas' disease. A crystal structure of cruzain, covalently inactivated by fluoromethyl ketone inhibitor 1 (Cbz-Phe-Ala-FMK), was used as a template to design potential inhibitors. Conformationally constrained gamma-lactams containing electrophilic aldehyde (12, 17, 18, 25, 26, and 29) or vinyl sulfone (43, 44, and 46) units were synthesized. Constrained lactam 26 had IC50 values of ca. 20 nM against the Leishmania major protease and ca. 50 nM versus falcipain, an important cysteine protease isolated from Plasmodium falciparum. However, all of the conformationally constrained inhibitors were weak inhibitors of cruzain, compared to unconstrained peptide aldehyde (e.g. 5 ) and vinyl sulfone inhibitors (e.g. 48, which proved to be an excellent inhibitor of cruzain with an apparent second order inhibition rate constant (k(inact)/Ki) of 634,000s(-1)M(-1). A significant reduction in activity was also observed with acyclic inhibitors 30 and 51 containing alpha-methyl phenylalanine residues at the P2 position. These data indicate that the pyrrolidinone ring, especially the quarternary center at P2, interferes with the normal substrate binding mode with cruzain, but not with falcipain or the leishmania protease.
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PMID:Structure-based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors. 992 4

Innate immunity directs the adaptive immune response by identifying antigens that are associated with infectious agents. Although some microbial antigens can be recognized by innate immune receptors, most cannot, and these require identification by some other means. The introduction of aldehydes into antigens by glycolaldehyde, which can be produced by activated neutrophils reacting with serine, or by the oxidation of an N-linked oligosaccharide with NaIO4, enhances by several orders of magnitude their immunogenicity in mice. The augmented immunogenicity requires the presence of an aldehyde on the antigen, and is not dependent on protein aggregation. An in vitro correlate of augmented immunogenicity is the enhanced presentation of glycolaldehyde-modified antigen to T cells by macrophages and bone marrow-derived dendritic cells. The potential clinical importance of this form of antigen modification is twofold: glycolaldehyde renders a model self antigen immunogenic, and it converts a relatively non-immunogenic malaria antigen, merozoite surface protein-1, into an effective immunogen. Thus, the tagging of antigens by the addition of aldehydes, which may be an innate immune mechanism to facilitate their recognition by the adaptive immune system, may have a role in the genesis of autoimmunity and the development of vaccines.
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PMID:Enhanced immunogenicity of aldehyde-bearing antigens: a possible link between innate and adaptive immunity. 1106 70

An improved method for the synthesis of (6'R)-6'-C-methylneplanocin A (RMNPA, 2), a potent S-adenosyl-L-homocysteine (AdoHcy) hydrolase inhibitor, was developed via a chelation-controlled stereoselective addition of MeTiCl(3) to the neplanocin A 6'-aldehyde derivative 6. Compound 2 effectively inhibited the growth of malaria parasites both in vitro and in vivo. The antimalarial EC(50) value of 2 against Plasmodium berghei in mice was 1.0 mg/kg/day, which was superior to that of chloroquine (EC(50) = 1.8 mg/kg/day).
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PMID:New neplanocin analogues. 12. Alternative synthesis and antimalarial effect of (6'R)-6'-C-methylneplanocin A, a potent AdoHcy hydrolase inhibitor. 1180 27


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