Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
|---|
| solid-phase synthesis and bioevaluation of lupeol-based libraries as antimalarial agents. | the use of the triterpenoid lupeol as a scaffold for the synthesis of lupeol-based libraries is described. lupeol was anchored to a solid support (rink amide/sieber amide) through aliphatic dicarboxylic acid moieties, which also served as a site for introducing diversity. the resulting polymer linked 3beta-o (resin-alkanoyl)-lup-20(29)-ene 3 was used to generate key intermediates 3beta-o (resin-alkanoyl)-30-bromo-lup-20(29)-ene 4 and 3beta-o (resin-alkanoyl)-30-amino-lup-20(29)-ene 6 for the gen ... | 2002 | 12270150 |
| function of region i and ii adhesive motifs of plasmodium falciparum circumsporozoite protein in sporozoite motility and infectivity. | the circumsporozoite protein of plasmodium falciparum contains two conserved motifs (regions i and ii) that have been proposed to interact with mosquito and vertebrate host molecules in the process of sporozoite invasion of salivary glands and hepatocytes, respectively. to study the function of this protein we have replaced the endogenous circumsporozoite protein gene of plasmodium berghei with that of p. falciparum and with versions lacking either region i or region ii. we show here that p. fal ... | 2002 | 12244064 |
| plasmodium berghei: routine production of pure gametocytes, extracellular gametes, zygotes, and ookinetes. | 2002 | 12243741 | |
| from noxiustoxin to scorpine and possible transgenic mosquitoes resistant to malaria. | scorpion venom contains different types of peptides toxic to a variety of organisms whose molecular targets have been described as mainly ion-channels of excitable cells where they cause impairment of function. based on mouse, cricket, and crustacean bioassays, specific toxins for each group of animals have been found. chromatographic techniques were used to isolate and chemically characterize these peptides. one of the best-studied peptides is noxiustoxin, a 39-amino acid residue-long peptide s ... | 2002 | 12234530 |
| requirement for tumor necrosis factor receptor 2 expression on vascular cells to induce experimental cerebral malaria. | using tumor necrosis factor receptor type 2 (tnfr2)-deficient mice and generating bone marrow chimeras which express tnfr2 on either hematopoietic or nonhematopoietic cells, we demonstrated the requirement for tnfr2 expression on tissue cells to induce lethal cerebral malaria. thus, tnfr2 on the brain vasculature mediates tumor necrosis factor-induced neurovascular lesions in experimental cerebral malaria. | 2002 | 12228317 |
| implications of time bomb model of ookinete invasion of midgut cells. | in this review, we describe the experimental observations that led us to propose the time bomb model of ookinete midgut invasion and discuss potential implications of this model when considering malaria transmission-blocking strategies aimed at arresting parasite development within midgut cells. a detailed analysis of the molecular interactions between anopheles stephensi midgut epithelial cells and plasmodium berghei parasites, as they migrate through midgut cells, revealed that ookinetes induc ... | 2002 | 12225921 |
| a role for the alpha-chain connecting peptide motif in mediating tcr-cd8 cooperation. | to generate peripheral t cells that are both self-mhc restricted and self-mhc tolerant, thymocytes are subjected to positive and negative selection. how the tcr discriminates between positive and negative selection ligands is not well understood, although there is substantial evidence that the cd4 and cd8 coreceptors play an important role in this cell fate decision. we have previously identified an evolutionarily conserved motif in the tcr, the alpha-chain connecting peptide motif (alpha-cpm), ... | 2002 | 12218110 |
| role of the tumor necrosis factor receptor 2 (tnfr2) in cerebral malaria in mice. | infection of susceptible mice with plasmodium berghei anka leads to a syndrome of severe or cerebral malaria. tumor necrosis factor (tnf) contributes to this syndrome, apparently by acting on its receptor 2 (tnfr2) because tnfr1-/- are susceptible, whereas tnfr2-/- mice are resistant. in this work, we confirmed the essential role of the tnfr2 in cerebral malaria because 6 to 8 days after plasmodium berghei anka infection, hypothermia, coma, and death were observed in +/+ or tnfr1-/-, but never i ... | 2002 | 12218076 |
| structure-activity relationships of the antimalarial agent artemisinin. 7. direct modification of (+)-artemisinin and in vivo antimalarial screening of new, potential preclinical antimalarial candidates. | on the basis of earlier reported quantitative structure-activity relationship studies, a series of 9beta-16-(arylalkyl)-10-deoxoartemisinins were proposed for synthesis. several of the new compounds 7 and 10-14 were synthesized employing the key synthetic intermediate 23. in a second approach, the natural product (+)-artemisinic acid was utilized as an acceptor for conjugate addition, and the resultant homologated acids were subjected to singlet oxygenation and acid treatment to provide artemisi ... | 2002 | 12213073 |
| stage-specific promoter activity from stably maintained episomes in plasmodium falciparum. | genomic dna is organised at its simplest level within phased arrays of nucleosomes, a structure key to the correct transcriptional regulation of the encoded genes. here we studied chromatin formation on dna transfected into plasmodium falciparum either as an episomal plasmid or following integration by homologous recombination. we show that stably maintained and replicated plasmid assembles phased arrays of nucleosomes and that a reporter gene is transcribed in an appropriate temporal manner. th ... | 2002 | 12204219 |
| neurotoxicity and efficacy of arteether related to its exposure times and exposure levels in rodents. | the neurotoxicity of beta-arteether (ae) is related to drug accumulation in blood due to slow and prolonged absorption from the intramuscular injection sites. in this efficacy and toxicity study of ae, the traditional sesame oil vehicle was replaced with cremophore to decrease the accumulation and toxicity of ae. dihydroartemisinin (dqhs), a more toxic and active metabolite of ae, was also analyzed. when administered at a daily dosage of 25 mg/kg for seven days, blood accumulation of ae with ses ... | 2002 | 12201585 |
| superoxide anion in anopheles albimanus hemolymph and midgut is toxic to plasmodium berghei ookinetes. | the mechanisms of plasmodium spp. elimination in resistant mosquitoes are not completely understood. some resistant anopheline strains are able to melanize plasmodium spp. ookinetes in their midguts. because quinoid compounds are potent catalysts for free radical generation and because these radicals can be generated in association with melanogenesis, it is probable that they play an important role in the elimination of parasites. the production of the superoxide anion (o-2) in the hemolymph and ... | 2002 | 12197117 |
| immuno-electron microscopic observation of plasmodium berghei ctrp localization in the midgut of the vector mosquito anopheles stephensi. | the subcellular localization of plasmodium berghei circumsporozoite protein and thrombospondin-related adhesive protein (pbctrp) in the invasive stage ookinete of p. berghei was studied in the midgut of anopheles stephensi by immuno-electron microscopic observations using polyclonal antibodies and immuno-gold labeling. pbctrp was found to be associated with the micronemes of a mature ookinete throughout the movement from the endoperitrophic space to the basal lamina of the midgut epithelium. pbc ... | 2002 | 12197111 |
| murine malaria is exacerbated by ctla-4 blockade. | cytolytic t lymphocyte-associated ag-4 (cd152) is a negatively regulating molecule, which is primarily expressed on t cells following their activation. in this study, we have examined the role of ctla-4 expression in experimental blood-stage malaria. similar to human malaria, ctla-4 is expressed on cd4(+) t cells of c57bl/6 mice after infection with plasmodium berghei. a kinetic analysis revealed that ctla-4 expression was increased on day 5 postinfection and reached a peak on day 9 postinfectio ... | 2002 | 12193697 |
| orally active, water-soluble antimalarial 3-aryltrioxanes: short synthesis and preclinical efficacy testing in rodents. | short chemical syntheses of four new antimalarial trioxanes are presented, starting with inexpensive and commercially available cyclohexanone. almost exclusive formation of the trioxane 12alpha-stereoisomers simplifies product purification. carboxyphenyltrioxanes 3 and 5 are thermally stable in air even at 60 degrees c for 24 h. when administered orally, these new carboxyphenyltrioxanes are highly efficacious in curing malaria-infected mice. important for their practical in vivo administration, ... | 2002 | 12190305 |
| reverse genetics in the mosquito anopheles gambiae: targeted disruption of the defensin gene. | anopheles gambiae, the major vector of human malaria parasite, is an important insect model to study vector-parasite interactions. here, we developed a simple in vivo double-stranded rna (dsrna) knockout approach to determine the function of the mosquito antimicrobial peptide gene defensin. we injected dsrna into adults and observed efficient and reproducible silencing of defensin. analysis of the knockdown phenotype revealed that this peptide is required for the mosquito antimicrobial defense a ... | 2002 | 12189180 |
| synthetic gpi as a candidate anti-toxic vaccine in a model of malaria. | the malaria parasite plasmodium falciparum infects 5-10% of the world's population and kills two million people annually. fatalities are thought to result in part from pathological reactions initiated by a malarial toxin. glycosylphosphatidylinositol (gpi) originating from the parasite has the properties predicted of a toxin; however, a requirement for toxins in general and gpi in particular in malarial pathogenesis and fatality remains unproven. as anti-toxic vaccines can be highly effective pu ... | 2002 | 12181569 |
| plasmodium: assessment of the antimalarial potential of trifluralin and related compounds using a rat model of malaria, rattus norvegicus. | a rodent model of malaria, plasmodium berghei was used to assess the antimalarial potential of dinitroaniline herbicides. trifluralin, pendimethalin, oryzalin, and benfluralin were all active against p. berghei in vitro at, or close to, submicromolar concentrations, with a rank order of potency similar to that against other protozoa. the dinitroanilines did not elicit a cytotoxic effect against a mammalian cell line at concentrations 100-fold higher than those for activity against p. berghei. ne ... | 2002 | 12173400 |
| bee venom phospholipase inhibits malaria parasite development in transgenic mosquitoes. | malaria kills millions of people every year, and new control measures are urgently needed. the recent demonstration that (effector) genes can be introduced into the mosquito germ line to diminish their ability to transmit the malaria parasite offers new hope toward the fight of the disease (ito, j., ghosh, a., moreira, l. a., wimmer, e. a. & jacobs-lorena, m. (2002) nature, 417, 452-455). because of the high selection pressure that an effector gene imposes on the parasite population, development ... | 2002 | 12167627 |
| identification, expression, and functional characterization of maebl, a sporozoite and asexual blood stage chimeric erythrocyte-binding protein of plasmodium falciparum. | maebl is a chimeric erythrocyte binding protein reported in rodent malaria parasites plasmodium yoelii and plasmodium berghei, that has the gene structure similar to erythrocyte binding proteins, but n-terminal homology to subdomains i and ii of apical membrane antigen-1. we report here the sequence analysis and gene structure of the plasmodium falciparum maebl gene. we have cloned and expressed a putative red cell binding domain, m2, of this gene in escherichia coli, purified the recombinant pr ... | 2002 | 12165387 |
| isolation and in vitro antiplasmodial activities of alkaloids from teclea trichocarpa: in vivo antimalarial activity and x-ray crystal structure of normelicopicine. | seven alkaloids have been isolated from teclea trichocarpa including four, normelicopicine (1), arborinine (2), skimmianine (6), and dictamnine (7), that are reported for the first time in addition to the previously reported alkaloids melicopicine (3), tecleanthine (4), and 6-methoxytecleanthine (5). the structure of 1 was confirmed by single-crystal x-ray crystallography. two alkaloids, 1 and 2, displayed limited in vitro activities against plasmodium falciparum strains hb3 and k1, but there ap ... | 2002 | 12141852 |
| proteoglycans mediate malaria sporozoite targeting to the liver. | malaria sporozoites are rapidly targeted to the liver where they pass through kupffer cells and infect hepatocytes, their initial site of replication in the mammalian host. we show that sporozoites, as well as their major surface proteins, the cs protein and trap, recognize distinct cell type-specific surface proteoglycans from primary kupffer cells, hepatocytes and stellate cells, but not from sinusoidal endothelia. recombinant plasmodium falciparum cs protein and trap bind to heparan sulphate ... | 2002 | 12139612 |
| synthesis and in vitro studies of novel pyrimidinyl peptidomimetics as potential antimalarial therapeutic agents. | a class of new pyrimidinyl peptidomimetic agents (compounds 1-6) were synthesized, and their in vitro antimalarial activities against plasmodium falciparum were evaluated. the core structure of the new agents consists of a substituted 5-aminopyrimidone ring and a michael acceptor side chain methyl 2-hydroxymethyl-but-2-enoate. the synthesis of 1-6 featured a baylis-hillman reaction of various aldehydes with methyl acrylate catalyzed by 1,4-diazabicyclo[2.2.2]octane (dabco) and a s(n)2' mitsunobu ... | 2002 | 12139460 |
| cell trafficking. malaria blood-stage parasite-specific cd4+ t cells after adoptive transfer into mice. | 2002 | 12125135 | |
| gene targeting in plasmodium berghei. | 2002 | 12125129 | |
| episomal transformation of plasmodium berghei. | 2002 | 12125128 | |
| construction of a gene library with mung bean nuclease-treated genomic dna. | 2002 | 12125123 | |
| maintenance of the plasmodium berghei life cycle. | 2002 | 12125122 | |
| in situ detection of rna in blood- and mosquito-stage malaria parasites. | 2002 | 12125119 | |
| short-chain aliphatic polysulfonates inhibit the entry of plasmodium into red blood cells. | several steps in the pathogenesis of a plasmodium falciparum infection depend on interactions of parasite surface proteins with negatively charged sugars on the surface of host cells such as sialate residues or glycosaminoglycans. for these reasons, our previous studies examining agents that interfere with heparan sulfate-protein binding during amyloidogenesis suggested that short-chain aliphatic polysulfonates may prove useful as antimalarial agents. a series of related polysulfonates were synt ... | 2002 | 12121942 |
| apoptosis in the malaria protozoan, plasmodium berghei: a possible mechanism for limiting intensity of infection in the mosquito. | death by apoptosis regulates cell numbers in metazoan tissues and it is mediated by activation of caspases and results in characteristic morphological and biochemical changes. we report here that the malaria protozoan, plasmodium berghei, exhibits features typical of metazoan apoptotic cells including condensation of chromatin, fragmentation of the nuclear dna and movement of phosphatidylserine from the inner to the outer lamellae of the cell membrane. in addition, proteins with caspase-like act ... | 2002 | 12117496 |
| identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain. | malaria is a complex infectious disease in which the host/parasite interaction is strongly influenced by host genetic factors. the consequences of plasmodial infections range from asymptomatic to severe complications like the neurological syndrome cerebral malaria induced by plasmodium falciparum in humans and plasmodium berghei anka in rodents. mice infected with p. berghei anka show marked differences in disease manifestation and either die from experimental cerebral malaria (ecm) or from hemo ... | 2002 | 12114535 |
| influence of antimalarial treatment on acquisition of immunity in plasmodium berghei nk65 malaria. | antimalarial treatments during primary plasmodium berghei nk65 infection in balb/c mice influenced the acquisition of protective immunity against reinfection. among subcurative treatments, lower doses better enable mice to acquire protective immunity than do higher doses. eradication of parasites from the start of infection did not promote protective immunity. | 2002 | 12093701 |
| hepatic kupffer cell phagocytotic function in rats with erythrocytic-stage malaria. | in the erythrocytic phase of malaria, kupffer cells show marked hypertrophy and hyperplasia and are filled with malarial pigment. however, phagocytic function in this state has not been well characterized. the aim of the present study was to use mouse plasmodium berghei to infect rats with malaria and study the phagocytic function and morphology of kupffer cells. | 2002 | 12084035 |
| [accumulation and effluxion of chloroquine in chloroquine-sensitive and chloroquine-resistant plasmodium berghei]. | to explore whether the difference in the amount of chloroquine (cq) accumulated in cq-resistant (cr) and in cq-sensitive (cs) p. berghei is involved in the infected erythrocytes (rbc) or in the parasites. | 1998 | 12078239 |
| [determination of polyamines in pyronaridine-sensitive and -resistant plasmodium berghei-infected erythrocytes]. | to understand the relationship between polyamine metabolism and pyronaridine resistance of malaria parasites. | 1998 | 12078217 |
| design and activity of antimicrobial peptides against sporogonic-stage parasites causing murine malarias. | insects produce several types of peptides to combat a broad spectrum of invasive pathogenic microbes, including protozoans. however, despite this defense response, infections are often established. our aim was to design novel peptides that produce high rates of mortality among protozoa of the genus plasmodium, the malaria parasites. using existing antimicrobial peptide sequences as templates, we designed and synthesized three short novel hybrids, designated vida1 to vida3. each has a slightly di ... | 2002 | 12069961 |
| antimalarial activities of ring-substituted bioimidazoles. | we report in vitro antimalarial activities against chloroquine sensitive and resistant plasmodium falciparum strains, and in vivo activities against plasmodium berghei in mice for four series of ring-substituted-l-histidines and histamines. | 2002 | 12067541 |
| deletion of t cells bearing the v beta8.1 t-cell receptor following mouse mammary tumor virus 7 integration confers resistance to murine cerebral malaria. | plasmodium berghei anka induces a fatal neurological syndrome known as cerebral malaria (cm) in susceptible mice. host genetic elements are among the key factors determining susceptibility or resistance to cm. analysis of mice of the same h-2 haplotype revealed that mouse mammary tumor virus 7 (mtv-7) integration into chromosome 1 is one of the key factors associated with resistance to neurological disease during p. berghei anka infection. we investigated this phenomenon by infecting a series of ... | 2002 | 12065512 |
| immune responses to liver-stage parasites: implications for vaccine development. | 2002 | 12058653 | |
| mouse models of blood-stage malaria infections: immune responses and cytokines involved in protection and pathology. | 2002 | 12058640 | |
| stromal cell derived factor 1 synthesis by spleen cells in rodent malaria, and the effects of in vivo supplementation of sdf-1alpha and cxcr4 receptor blocker. | the mechanisms of malaria parasite clearance in the host are not well understood, but are ascribed to the intact spleen, the site for parasite clearance. the infection induces a huge increase in spleen volume and cellularity. there is, however, a lack of studies on the splenic production of chemokines, which are small proteins that control homing and activation of immune cells and must be crucial for organized tissue growth. we studied the spleen cell production of sdf-1, a primordial chemokine ... | 2002 | 12057854 |
| potent antimalarial febrifugine analogues against the plasmodium malaria parasite. | although febrifugine (1) and isofebrifugine (2), alkaloids isolated from roots of the dichroa febrifuga plant, show powerful antimalarial activity against plasmodium falciparum, strong side effects such as the emetic effect have precluded their clinical use against malaria. however, their antimalarial potency makes them attractive substances as leads for developing new types of chemotherapeutic antimalarial drugs. thus, we have evaluated the in vitro antimalarial activity of the analogues of feb ... | 2002 | 12036365 |
| transgenic anopheline mosquitoes impaired in transmission of a malaria parasite. | malaria is estimated to cause 0.7 to 2.7 million deaths per year, but the actual figures could be substantially higher owing to under-reporting and difficulties in diagnosis. if no new control measures are developed, the malaria death toll is projected to double in the next 20 years. efforts to control the disease are hampered by drug resistance in the plasmodium parasites, insecticide resistance in mosquitoes, and the lack of an effective vaccine. because mosquitoes are obligatory vectors for m ... | 2002 | 12024215 |
| locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principle mediator of murine cerebral malaria. | cerebral malaria (cm) causes death in children and nonimmune adults. tnf-alpha has been thought to play a key role in the development of cm. in contrast, the role of the related cyto-kine lymphotoxin alpha (ltalpha) in cm has been overlooked. here we show that ltalpha, not tnfalpha, is the principal mediator of murine cm. mice deficient in tnfalpha (b6.tnfalpha-/-) were as susceptible to cm caused by plasmodium berghei (anka) as c57bl/6 mice, and died 6 to 8 d after infection after developing ne ... | 2002 | 12021316 |
| maebl is essential for malarial sporozoite infection of the mosquito salivary gland. | malarial sporozoites mature in the oocysts formed in the mosquito midgut wall and then selectively invade the salivary glands, where they wait to be transmitted to the vertebrate host via mosquito bite. invasion into the salivary gland has been thought to be mediated by specific ligand-receptor interactions, but the molecules involved in these interactions remain unknown. maebl is a single transmembrane-like protein that is structurally related to merozoite adhesive proteins. we found maebl of t ... | 2002 | 12021311 |
| antimalarial activity of medicinal plants used in traditional medicine in s. tomé and príncipe islands. | the present study investigates the antimalarial activity of 13 medicinal plants used in traditional medicine in s. tomé and príncipe (stp) islands in the gulf of guinea, aiming at identifying the most effective plants for further research. fieldwork was carried out with the collaboration of 37 traditional healers from both islands, during an ethnobotanical study, which was conducted from 1993 to 1999. our results indicate that the traditional healers in stp use several medicinal plants against f ... | 2002 | 12020924 |
| expression of d7 and d7-related proteins in the salivary glands of the human malaria mosquito anopheles stephensi. | full-length cdna clones encoding d7 (ansd7) and d7-related (ansd7r1) secreted salivary gland proteins were isolated from anopheles stephensi. corresponding proteins were separated by sds-page and analysed by n-terminal sequencing, which also identified a second d7-related protein (ansd7r2). ansd7 encodes a protein of 37 kda, ansd7r1 of 18 kda, and ansd7r2 of 16 kda. polyclonal antibodies against recombinant ansd7 showed immunological cross-reactivity with the d7-related proteins, and alignment d ... | 2002 | 12000641 |
| mitochondrial nadh dehydrogenase from plasmodium falciparum and plasmodium berghei. | the mitochondrial electron transport system is necessary for growth and survival of malarial parasites in mammalian host cells. nadh dehydrogenase of respiratory complex i was demonstrated in isolated mitochondrial organelles of the human parasite plasmodium falciparum and the mouse parasite plasmodium berghei by using the specific inhibitor rotenone on oxygen consumption and enzyme activity. it was partially purified by two sequential steps of fast protein liquid chromatographic techniques from ... | 2002 | 11971654 |
| the role of il-18 in blood-stage immunity against murine malaria plasmodium yoelii 265 and plasmodium berghei anka. | a possible protective role of il-18 in host defense against blood-stage murine malarial infection was studied in balb/c mice using a nonlethal strain, plasmodium yoelii 265, and a lethal strain, plasmodium berghei anka. infection induced an increase in mrna expression of il-18, il-12p40, ifn-gamma, and tnf-alpha in the case of p. yoelii 265 and an increase of il-18, il-12p40, and ifn-gamma in the case of p. berghei anka. the timing of mrna expression of il-18 in both cases was consistent with a ... | 2002 | 11971017 |
| [synthesis of primaquine analogues and their antimalarial activity in mice]. | ten 4-methyl-5-substituted-phenoxy-6-methoxy-8-[(1-ethyl-4-amino) butylamino] quinolines (10a-j) have been synthesized and evaluated preliminarily for both suppressive and causal prophylactic antimalarial activities. the results of preliminary screening test showed that three of these compounds exhibited significant activity against plasmodium yoelii in mice, among which 10c was 4-8 times as effective as primaquine. moreover, 10c was superior to primaquine in suppressive test against plasmodium ... | 1998 | 11938965 |
| changes in schizogony and drug response in two lines of rodent plasmodium, p. berghei nk 65 and p. berghei anka. | white mice were infected with two strains, anka and nk 65, of plasmodium berghei. the parasites were subjected to chloroquine pressure (60 mg/kg at each passage) during 20 passages. we then compared the behaviour of the strains as they acquired chemoresistance. the drug resistance was estimated by the 2% delay time test (d2%), and the schizogonic rhythm by the synchronicity index (si). before drug pressure, the anka strain had a d2% of 4.34, and a si of 0.2. this strain became highly drug resist ... | 2002 | 11938696 |
| induced immunity against the mosquito anopheles stephensi (diptera: culicidae): effects of cell fraction antigens on survival, fecundity, and plasmodium berghei (eucoccidiida: plasmodiidae) transmission. | two subeellular fractions from the midgut of the malaria mosquito anopheles stephensi (liston) were used to immunize balb/c mice. mice were subsequently infected with the rodent malaria parasite plasmodium berghei (vineke & lips), and the effects of anti-mosquito immunity on mosquito survival and fecundity and on parasite transmission were investigated. mosquitoes were infected directly from mice (in vivo) or by feeding cultured ookinetes through a membrane (in vitro). infections were monitored ... | 2002 | 11931258 |
| the mechanism and significance of deletion of parasite-specific cd4(+) t cells in malaria infection. | it is thought that both helper and effector functions of cd4(+) t cells contribute to protective immunity to blood stage malaria infection. however, malaria infection does not induce long-term immunity and its mechanisms are not defined. in this study, we show that protective parasite-specific cd4(+) t cells were depleted after infection with both lethal and nonlethal species of rodent plasmodium: it is further shown that the depletion is confined to parasite-specific t cells because (a) ovalbum ... | 2002 | 11927632 |
| plasmodium sporozoite invasion into insect and mammalian cells is directed by the same dual binding system. | plasmodium sporozoites, the transmission form of the malaria parasite, successively invade salivary glands in the mosquito vector and the liver in the mammalian host. sporozoite capacity to invade host cells is mechanistically related to their ability to glide on solid substrates, both activities depending on the transmembrane protein trap. here, we show that loss-of- function mutations in two adhesive modules of the trap ectodomain, an integrin-like a-domain and a thrombospondin type i repeat, ... | 2002 | 11927544 |
| levels of circumsporozoite protein in the plasmodium oocyst determine sporozoite morphology. | the sporozoite stage of the plasmodium parasite is formed by budding from a multinucleate oocyst in the mosquito midgut. during their life, sporozoites must infect the salivary glands of the mosquito vector and the liver of the mammalian host; both events depend on the major sporozoite surface protein, the circumsporozoite protein (cs). we previously reported that plasmodium berghei oocysts in which the cs gene is inactivated do not form sporozoites. here, we analyzed the ultrastructure of p.ber ... | 2002 | 11927543 |
| susceptibility to experimental cerebral malaria induced by plasmodium berghei anka in inbred mouse strains recently derived from wild stock. | the neurological syndrome caused by plasmodium berghei anka in rodents partially mimics the human disease. several rodent models of cerebral malaria (cm) exist for the study of the mechanisms that cause the disease. however, since common laboratory mouse strains have limited gene pools, the role of their phenotypic variations causing cm is restricted. this constitutes an obstacle for efficient genetic analysis relating to the pathogenesis of malaria. most common laboratory mouse strains are susc ... | 2002 | 11895970 |
| a rodent malaria, plasmodium berghei, is experimentally transmitted to mice by merely probing of infective mosquito, anopheles stephensi. | we found that infection of a rodent malaria, plasmodium berghei, occurred when the sporozoites were injected into the skin, the muscle, the peritoneal cavity and the tail end. mice, which were injected with sporozoites in the tail end and had the site cut 5 min later, did not develop malaria. we also found that mice developed malaria when malaria infective mosquitoes, anopheles stephensi, were forced not to take blood but only to probe into the skin. moreover, the mice probed by the infective mo ... | 2002 | 11880224 |
| haptoglobin and malaria. | haptoglobin gene knockout mice and wild-type controls were infected with plasmodium berghei anka or plasmodium chabaudi. the peak parasitaemia and parasite burden were higher in hp-/- mice than in hp+/+ mice. the increase in spleen weight following malaria infection was smaller in hp-/- mice than in hp+/+ animals. the occurrence of cerebral malaria in p. berghei anka infection was not different in hp gene knockout mice and their controls. | 2001 | 11865983 |
| thrombocytopenia in an animal model of malaria is associated with an increased caspase-mediated death of thrombocytes. | infection of mice with plasmodium berghei anka (pba) leads to a thrombocytopenia, due to a reduced platelet life span, eventually associated with a syndrome of severe or cerebral malaria (cm). thrombocytopenia was associated with an increase in the number of microparticles (mcp) in plasma. more than >60% of these mcp were of platelet origin, as seen by staining with an anti-platelet antibody. the thrombocytopenia and the amount of mcp were decreased in mice treated with anti cd40l mab, suggestin ... | 2002 | 11865192 |
| mechanism-based design of parasite-targeted artemisinin derivatives: synthesis and antimalarial activity of new diamine containing analogues. | the potent antimalarial activity of chloroquine against chloroquine-sensitive strains can be attributed, in part, to its high accumulation in the acidic environment of the heme-rich parasite food vacuole. a key component of this intraparasitic chloroquine accumulation mechanism is a weak base "ion-trapping" effect whereupon the basic drug is concentrated in the acidic food vacuole in its membrane-impermeable diprotonated form. by the incorporation of amino functionality into target artemisinin a ... | 2002 | 11855985 |
| hepatic hematopoiesis in adult mouse during experimental rodent malaria. | during rodent malaria the development of the hematopoiesis in the liver was observed. this fact was used as a model for the study of the conditions and the features of the extramedullary hematopoietic differentiation, following the state of anaemia induced by parasitemia with plasmodium berghei. histological and ultrastructural data on the hepatic hematopoiesis are presented. | 1999 | 11845448 |
| demonstrating the validity of natural products as anti-infective drugs. | this presentation reviews the synthetic or classical development pathway of drug development and contrasts it with developing natural products as drugs. also presented is an example of a traditional medicine that has been developed from a natural product and has become a "new/old" antiparasitic drug used in the treatment of malaria. the classic paradigm of synthetic drug development breaks down into drug discovery, drug design, preclinical studies, and clinical studies. this paradigm, constructe ... | 2001 | 11822638 |
| complete development of mosquito phases of the malaria parasite in vitro. | methods for reproducible in vitro development of the mosquito stages of malaria parasites to produce infective sporozoites have been elusive for over 40 years. we have cultured gametocytes of plasmodium berghei through to infectious sporozoites with efficiencies similar to those recorded in vivo and without the need for salivary gland invasion. oocysts developed extracellularly in a system whose essential elements include co-cultured drosophila s2 cells, basement membrane matrix, and insect tiss ... | 2002 | 11809973 |
| topology and replication of a nuclear episomal plasmid in the rodent malaria plasmodium berghei. | the rodent malaria plasmodium berghei is one of a small number of species of plasmodium that can currently be genetically transformed through experimentally controlled uptake of exogenous dna by bloodstage parasites. circular dna containing a selectable marker replicates and is maintained under selection pressure in a randomly segregating episomal form during the first weeks after transformation. in this study, using pulsed field gel electrophoresis and ionising radiation, we show that in dividi ... | 2002 | 11809885 |
| new neplanocin analogues. 12. alternative synthesis and antimalarial effect of (6'r)-6'-c-methylneplanocin a, a potent adohcy hydrolase inhibitor. | 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(5 ... | 2002 | 11806727 |
| enhanced cd8 t cell immunogenicity and protective efficacy in a mouse malaria model using a recombinant adenoviral vaccine in heterologous prime-boost immunisation regimes. | recombinant replication-defective adenovirus expressing the cs gene from plasmodium berghei (ad-pbcs) was found to induce a strong cd8(+) t cell response after intra-dermal or -muscular immunisation. boosting of an adenovirus-primed immune response with the replication-impaired poxvirus, modified vaccinia virus ankara (mva) led to enhanced immunogenicity and substantial protective efficacy. the recombinant adenoviral vaccine was capable of boosting to protective levels a cd8(+) t cell response p ... | 2002 | 11803063 |
| association of a determinant on mouse chromosome 18 with experimental severe plasmodium berghei malaria. | experimental severe malaria (esm; also known as experimental cerebral malaria) is an acute lethal syndrome caused by infection with plasmodium berghei anka and associated with coma and other neurological manifestations in mice. various inbred strains of mice exhibit differences in susceptibility to the development of esm. for example, c57bl/6 mice are highly susceptible and dba/2 mice are relatively resistant. we report here the results of a genomewide scan for host genomic regions that control ... | 2002 | 11796577 |
| the role of plasmodium berghei ookinete proteins in binding to basal lamina components and transformation into oocysts. | the ookinete is a motile form of the malaria parasite that travels from the midgut lumen of the mosquito, invades the epithelial cells and settles beneath the basal lamina. the events surrounding cessation of ookinete motility and its transformation into an oocyst are poorly understood, but interaction between components of the basal lamina and the parasite surface has been implicated. here we report that interactions occur between basal lamina constituents and ookinete proteins and that these i ... | 2002 | 11796126 |
| effect of solanum nudum extracts on the liver of mice infected with plasmodium berghei. | the plant solanum nudum has been used by the community of tumaco (nariño, colombia) as a cure for malaria. our group has confirmed the in vitro antimalarial activity against the strain of plasmodium falciparum fcb-2. during our in vivo studies on the therapeutic effect of solanum nudum extracts on mice infected with plasmodium berghei, we observed yellowish tint in the palms of mice treated with the aqueous extract via i.p. at a concentration of 2.4% w/vol. this finding suggested the need to car ... | 2001 | 11789590 |
| incidence of apoptosis in the lymphoid organs of normal or malaria infected mice is decreased in cd18 and urokinase-receptor (upar, cd87) deficient mice. | incidence of apoptosis was investigated in the spleen and lymph nodes of +/+, cd18 -/- and urokinase receptor (upar, cd87) -/- mice, untreated or plasmodium berghei anka (pba) infected. in non infected mice, incidence of apoptosis was lower in the lymph nodes of cd18 -/- and upar -/- than in +/+ mice, as seen by facs analysis to count the number of hypodiploid and annexin-v binding cells. infection of mice with pba resulted in a marked increase in the size of spleen and lymph nodes 7-8 days afte ... | 2001 | 11785668 |
| effects of dna vaccine in murine malaria using a full-length cdna library. | in an attempt to develop a novel malaria vaccine, we constructed a full-length cdna library from the erythrocytic-stage parasites of plasmodium berghei anka strain using the plasmid vector pce-fl, which is driven by an ef321 promoter and a cmv-ie enhancer. here we report the initial trial to screen this library for dna vaccine candidates against malaria parasite infection in mice. the library of p. berghei was divided into five groups, each representing 2,000 independent clones. eight female bal ... | 2001 | 11758646 |
| profiling the malaria genome: a gene survey of three species of malaria parasite with comparison to other apicomplexan species. | we have undertaken the first comparative pilot gene discovery analysis of approximately 25,000 random genomic and expressed sequence tags (ests) from three species of plasmodium, the infectious agent that causes malaria. a total of 5482 genome survey sequences (gsss) and 5582 ests were generated from mung bean nuclease (mbn) and cdna libraries, respectively, of the anka line of the rodent malaria parasite plasmodium berghei, and 10,874 gsss generated from mbn libraries of the salvador i and bele ... | 2001 | 11738710 |
| comparative genomics in plasmodium: a tool for the identification of genes and functional analysis. | comparative genomics allows inferences to be drawn about the coding potential of related genomes, and the evolutionary forces that have influenced genome organisation. early comparisons have indicated that there is significant synteny (conserved physical association of genes) between the human parasite plasmodium falciparum and the malaria parasites of rodents, such as plasmodium berghei. the various plasmodium genome initiatives have now provided the opportunity to perform comparative genomics ... | 2001 | 11738705 |
| antimalarial alkoxylated and hydroxylated chalcones [corrected]: structure-activity relationship analysis. | chalcones with 2',3',4'-trimethoxy, 2',4'-dimethoxy, 4'-methoxy, 4'-ethoxy, 2',4'-dihydroxy, and 4'-hydroxy groups on ring b were synthesized and evaluated in vitro against plasmodium falciparum (k1) in a [3h] hypoxanthine uptake assay. the other ring a was quinoline, pyridine, naphthalene, or phenyl rings with electron-donating or electron-withdrawing substituents of varying lipophilicities. trimethoxy 6 and 27, dimethoxy 7, 8, 29, and methoxy 31 analogues had good in vitro activities (ic(50) < ... | 2001 | 11728189 |
| virus-like particles as vaccine adjuvants. | virus-like particles (vlps) consist of one or more viral coat proteins that assemble into particles. they can be taken up by antigen presenting cells (apc), peptides derived from them are presented on mhc class i molecules at the cell surface, and thereby prime a cd8+ t cell response, either against the particle-forming protein itself (such as hepatitis b surface antigen) or additional peptide sequences that are produced as fusions with the particle-forming protein. this article describes the pr ... | 2001 | 11725486 |
| isolation and biological evaluation of filiformin, plakortide f, and plakortone g from the caribbean sponge plakortis sp. | the bioassay- and spectroscopic-guided fractionation of the antimalarial extract from a jamaican sponge, plakortis sp., resulted in the isolation of three metabolites. the previously reported bromoaromatic filiformin (1) was obtained from our sample of plakortis sp., and the potential origins of this compound are discussed. the peroxide-containing metabolite, plakortide f (2), is a more typical plakortis metabolite and was shown to exhibit significant activity against plasmodium falciparum in vi ... | 2001 | 11720540 |
| cd8beta endows cd8 with efficient coreceptor function by coupling t cell receptor/cd3 to raft-associated cd8/p56(lck) complexes. | the extraordinary sensitivity of cd8+ t cells to recognize antigen impinges to a large extent on the coreceptor cd8. while several studies have shown that the cd8beta chain endows cd8 with efficient coreceptor function, the molecular basis for this is enigmatic. here we report that cell-associated cd8alphabeta, but not cd8alphaalpha or soluble cd8alphabeta, substantially increases the avidity of t cell receptor (tcr)-ligand binding. to elucidate how the cytoplasmic and transmembrane portions of ... | 2001 | 11714755 |
| a prodrug form of a plasmodium falciparum glutathione reductase inhibitor conjugated with a 4-anilinoquinoline. | glutathione (gsh), which is known to guard plasmodium falciparum from oxidative damage, may have an additional protective role by promoting heme catabolism. an elevation of gsh content in parasites leads to increased resistance to chloroquine (cq), while gsh depletion in resistant p. falciparum strains is expected to restore the sensitivity to cq. high intracellular gsh levels depend inter alia on the efficient reduction of gssg by glutathione reductase (gr). on the basis of this hypothesis, we ... | 2001 | 11708927 |
| cd8(+)-t-cell depletion ameliorates circulatory shock in plasmodium berghei-infected mice. | the plasmodium berghei-infected mouse model is a well-recognized model for human cerebral malaria. mice infected with p. berghei exhibit (i) metabolic acidosis (ph < 7.3) associated with elevated plasma lactate concentrations, (ii) significant (p < 0.05) vascular leakage in their lungs, hearts, kidneys, and brains, (ii) significantly (p < 0.05) higher cell and serum glutamate concentrations, and (iv) significantly (p < 0.05) lower mean arterial blood pressures. because these complications are si ... | 2001 | 11705906 |
| the gametocyte-activating factor xanthurenic acid stimulates an increase in membrane-associated guanylyl cyclase activity in the human malaria parasite plasmodium falciparum. | sex is an obligate step in the life cycle of the malaria parasite and occurs in the midgut of the mosquito vector. with both plasmodium falciparum and plasmodium berghei, the tryptophan metabolite xanthurenic acid induces the release of motile male gametes from red blood cells (exflagellation), a prerequisite for fertilization. the addition of cgmp or phosphodiesterase inhibitors to cultures of mature gametocytes has also been shown to stimulate exflagellation. here, we demonstrate that there is ... | 2001 | 11703675 |
| plasmodium berghei infection in mice induces liver injury by an il-12- and toll-like receptor/myeloid differentiation factor 88-dependent mechanism. | malaria, caused by infection with plasmodium spp., is a life cycle-specific disease that includes liver injury at the erythrocyte stage of the parasite. in this study, we have investigated the mechanisms underlying plasmodium berghei-induced liver injury, which is characterized by the presence of apoptotic and necrotic hepatocytes and dense infiltration of lymphocytes. although both il-12 and il-18 serum levels were elevated after infection, il-12-deficient, but not il-18-deficient, mice were re ... | 2001 | 11698470 |
| enhanced immunostimulant activity and protective effect of a synthetic lipopeptide after liposomization against plasmodium berghei infection in mice. | the immunostimulant activity of non-pyrogenic, sugar-free immunomodulator lipopeptide, ala-d-glu(gly-lys-co.c11h23)-nh2 (comp. no 84/201), and its liposomized formulation has been studied. liposomization of this lipopeptide significantly enhanced its antigen specific as well as nonspecific immune responses, as compared to the free lipopeptide. the liposomized formulation of lipopeptide significantly stimulated both the antibody and delayed-type hypersensitivity responses in balb/c mice, and also ... | 2001 | 11697027 |
| phenoxypropoxybiguanides, prodrugs of dhfr-inhibiting diaminotriazine antimalarials. | a total of 34 analogues of the biguanide ps-15 (5s), a prodrug of the diaminotriazine wr-99210 (8s), have been prepared. several of them, such as 5b (ps-33) and 5m (ps-26), maintain or exceed the in vivo activity of ps-15 while not requiring the use of highly regulated starting materials. the putative diaminotriazine metabolites of these new analogues (compounds 8) have also been prepared and shown to maintain the activity against resistant p. falciparum strains. the structure-activity relations ... | 2001 | 11689078 |
| targeting plasmodium ligands on mosquito salivary glands and midgut with a phage display peptide library. | despite vast efforts and expenditures in the past few decades, malaria continues to kill millions of persons every year, and new approaches for disease control are urgently needed. to complete its life cycle in the mosquito, plasmodium, the causative agent of malaria, has to traverse the epithelia of the midgut and salivary glands. although strong circumstantial evidence indicates that parasite interactions with the two organs are specific, hardly any information is available about the interacti ... | 2001 | 11687659 |
| gambicin: a novel immune responsive antimicrobial peptide from the malaria vector anopheles gambiae. | a novel mosquito antimicrobial peptide, gambicin, and the corresponding gene were isolated in parallel through differential display-pcr, an expressed sequence tag (est) project, and characterization of an antimicrobial activity in a mosquito cell line by reverse-phase chromatography. the 616-bp gambicin orf encodes an 81-residue protein that is processed and secreted as a 61-aa mature peptide containing eight cysteines engaged in four disulfide bridges. gambicin lacks sequence homology with othe ... | 2001 | 11606751 |
| [synthesis and antimalarial activities of fluorenemethanols]. | for the purpose of improving the oral antimalarial activities of the fluorenemethanols (reported by us in previous articles) which were less effective by oral than by subcutaneous administration, 24 alpha-(alkylaminomethyl)-2, 7-dichloro-9-substituted benzylidene-4-fluorenemethanols (iii) were synthesized. the results of preliminary screenings demonstrated that five compounds (no. 1-4, 8) exhibited significant antimalarial activities against plasmodium berghei nk65 strain in mice by oral adminis ... | 1997 | 11596209 |
| potent antimalarial activities of polyether antibiotic, x-206. | in the course of our screening program to discover antimalarial antibiotics, which are active against drug resistant plasmodium falciparum in vitro and rodents infected with p. berghei in vivo, from the culture broth of microorganisms, we found a selective and potent active substance produced by an actinomycete strain k99-0413. it was identified as a known polyether antibiotic, x-206. we also compared the in vitro antimalarial activities and cytotoxicities of 12 known polyethers with x-206. amon ... | 2001 | 11592502 |
| nitric oxide and reactive nitrogen intermediates during lethal and nonlethal strains of murine malaria. | the virulence of plasmodia depends partly on the strain of parasite and partly on the host. in this study, plasmodium berghei n/13/1a/4/203 caused the death of mice, whereas plasmodium chabaudi chabaudi as was not lethal. current opinion is that nitric oxide (no) and other reactive nitrogen intermediates (rni) are produced in several host organs during malaria to resist infection or produce tissue damage. no and rni production in blood or plasma, brain, liver and spleen in mf1 mice was investiga ... | 2001 | 11589778 |
| pathogenesis of cerebral malaria: recent experimental data and possible applications for humans. | malaria still is a major public health problem, partly because the pathogenesis of its major complication, cerebral malaria, remains incompletely understood. experimental models represent useful tools to better understand the mechanisms of this syndrome. here, data generated by several models are reviewed both in vivo and in vitro; we propose that some pathogenic mechanisms, drawn from data obtained from experiments in a mouse model, may be instrumental in humans. in particular, tumor necrosis f ... | 2001 | 11585786 |
| characterization and identification of exflagellation-inducing factor in the salivary gland of anopheles stephensi (diptera: culicidae). | gamete activation factor (gaf) induces exflagellation of plasmodium microgametes. we found gaf in the salivary glands of female mosquitoes, anopheles stephensi. the exflagellation was induced in a concentration-dependent manner in the supernatant of salivary gland's crude homogenate. the exflagellation-inducing activity in the salivary gland was higher than that in the midgut and the head. gaf in the salivary glands was found to be heat stable and low molecular weight (<3000 molecular weight). a ... | 2001 | 11573943 |
| immune-mediated parasite clearance in mice infected with plasmodium berghei following treatment with manzamine a. | manzamine a, a sponge-derived alkaloid, was recently shown to possess in vivo antimalarial activity against the blood stages of the rodent malaria parasite plasmodium berghei. a single intraperitoneal dose of 100 micromol/kg of manzamine a suppressed parasite growth but was followed by parasite recrudescence. forty percent of mice with recrudescing parasites were able to recover and clear the fulminating parasitaemia. examination of sera from these mice revealed that infected mice treated with m ... | 2001 | 11570556 |
| protection of mice from malaria after co-administration of recombinant mouse granulocyte-macrophage colony- stimulating factor and methionine-enkephalin. | the protective effect of co-administration of recombinant mouse granulocyte-macrophage colony-stimulating factor (rmgm-csf) and synthetic peptide met-enkephalin (m-enk) against blood-induced plasmodium berghei infection in swiss mice was investigated. mice co-administered with rmgm-csf (10.0 mug/kg) and m-enk (2.0 mg/kg) x 3/day, i.p., beginning on day -1 and continuing through day +4 after the initiation of infection, showed significant suppression (p < 0.05) (sometimes even complete eliminatio ... | 2001 | 11566634 |
| is ischemia involved in the pathogenesis of murine cerebral malaria? | sequestration of parasitized erythrocytes in the central nervous system microcirculation and increased cerebrospinal fluid lactate are prominent features of cerebral malaria (cm), suggesting that sequestration causes mechanical obstruction and ischemia. to examine the potential role of ischemia in the pathogenesis of cm, plasmodium berghei anka (pba) infection in cba mice was compared to infection with p. berghei k173 (pbk) which does not cause cm (the non-cm model, ncm). cerebral metabolite poo ... | 2001 | 11549603 |
| synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents. | the indoloquinoline alkaloid cryptolepine 1 has potent in vitro antiplasmodial activity, but it is also a dna intercalator with cytotoxic properties. we have shown that the antiplasmodial mechanism of 1 is likely to be due, at least in part, to a chloroquine-like action that does not depend on intercalation into dna. a number of substituted analogues of 1 have been prepared that have potent activities against both chloroquine-sensitive and chloroquine-resistant strains of plasmodium falciparum a ... | 2001 | 11543688 |
| antimalarial simplified 3-aryltrioxanes: synthesis and preclinical efficacy/toxicity testing in rodents. | a streamlined five-step chemical synthesis of rationally designed, simplified 3-aryltrioxane 8a is described. a noteworthy feature of this synthetic scheme is use of air rather than expensive molecular oxygen as the source of the pharmacologically critical peroxide unit in trioxane 8a. this simplified acetal trioxane carboxylic acid 8a is thermally stable, and it is hydrolytically stable in water even at 40 degrees c and ph 7.4 for at least 7 days. preclinical evaluation of this water-soluble sy ... | 2001 | 11543673 |
| antimalarial t-butylperoxyamines. | twelve t-butylperoxyamines (6-17) were synthesized as targeted antimalarials and evaluated for antimalarial activity in vivo against plasmodium berghei in mice and in vitro against both chloroquine sensitive and chloroquine resistant strains of plasmodium falciparum. compound 8 was found to have highest potency with activity at 80 and 160mg/kg dose in vivo and compound 11 exhibited highest efficacy in vitro. | 2001 | 11527712 |
| synthesis of quinolinyl chalcones and evaluation of their antimalarial activity. | quinolinyl chalcones were synthesized and evaluated for their inhibition of the plasmodium falciparum cystein protease falcipain and their activity against cultured p. falciparum parasites. they were also tested for in vivo efficacy in a rodent p. berghei model. their activity against falcipain and as antimalarials was moderate, but antimalarial activity was probably not due to the inhibition of falcipain and may follow a different mechanism. 1-(2,4-dichlorophenyl)-3-[3-(2-chloro-6,7-dimethoxiqu ... | 2001 | 11525846 |
| phagocyte-derived reactive oxygen species and the immunology and pathology of murine malaria. | 2001 | 11523600 | |
| the role of cerebral oedema in the pathogenesis of cerebral malaria. | it has been suggested that sequestration of parasitized red blood cells might contribute to the pathogenesis of cerebral malaria (cm), by hypoxia causing either: (i) compensatory vasodilatation with a resultant increase in the brain volume; or (ii) enhancing cytokine-induced nitric oxide (no) production via induction of inducible no synthase (inos). available evidence suggests that cerebral oedema is the initiating and probably the most important factor in the pathogenesis of murine cm. the rele ... | 2001 | 11523587 |