Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
|---|
| o-alkoxyamidine prodrugs of furamidine: in vitro transport and microsomal metabolism as indicators of in vivo efficacy in a mouse model of trypanosoma brucei rhodesiense infection. | five o-alkoxyamidine analogues of the prodrug 2,5-bis[4-methoxyamidinophenyl]furan were synthesized and evaluated against trypanosoma brucei rhodesiense in the stib900 mouse model by oral administration. the observed in vivo activity of these prodrugs demonstrates that compounds with an o-methoxyamidine or o-ethoxyamidine group effectively cured all trypanosome-infected mice, whereas prodrugs with larger side-chains did not completely cure the mice. permeability across caco-2 cell monolayers and ... | 2004 | 15294005 |
| sleeping sickness in brothers in london. | brothers 9 and 14 years of age presented in london with fever and skin lesions after a safari in east africa. malaria films were negative, but trypanosomes were seen in blood films and chancre fluid. sleeping sickness should be considered in children returning from east africa. | 2004 | 15361733 |
| anthranoid compounds with antiprotozoal activity from vismia orientalis. | a phytochemical investigation of the 80% ethanolic extract of stem bark of vismia orientalis engl. (guttiferae or clusiaceae), a plant used in traditional medicine in tanzania, resulted in the isolation and spectroscopic characterisation of 3-geranyloxy-6-methyl-1,8-dihydroxyanthraquinone, emodin, vismione d and bianthrone a1. vismione d exhibited a broad range of antiprotozoal activities against trypanosoma brucei rhodesiense and t. cruzi (ic50 < 10 micrograms/ml), leishmania donovani (ic50 0.3 ... | 2004 | 15368649 |
| dicationic biphenyl benzimidazole derivatives as antiprotozoal agents. | a series of biphenyl benzimidazoles diamidines 6a-i were synthesized from their respective diamidoximes, through the bis-o-acetoxyamidoxime followed by hydrogenation in glacial acetic acid/ethanol in the presence of pd-c. the target compounds contain hydroxy and/or methoxy substituted 1,3-phenyl groups as the central spacer between the two amidino bearing aryl groups. all of the diamidines showed strong dna affinities as judged by high deltatm values with poly(da.dt)2, which varied with structur ... | 2004 | 15388167 |
| severity of human african trypanosomiasis in east africa is associated with geographic location, parasite genotype, and host inflammatory cytokine response profile. | the mechanisms underlying virulence in human african trypanosomiasis are poorly understood, although studies with experimental mice suggest that unregulated host inflammatory responses are associated with disease severity. we identified two trypanosomiasis foci with dramatically different disease virulence profiles. in uganda, infections followed an acute profile with rapid progression to the late stage (meningoencephalitic infection) in the majority of patients (86.8%). in contrast, infections ... | 2004 | 15557627 |
| african trypanosome interactions with an in vitro model of the human blood-brain barrier. | the neurological manifestations of sleeping sickness in man are attributed to the penetration of the blood-brain barrier (bbb) and invasion of the central nervous system by trypanosoma brucei gambiense and trypanosoma brucei rhodesiense. however, how african trypanosomes cross the bbb remains an unresolved issue. we have examined the traversal of african trypanosomes across the human bbb using an in vitro bbb model system constructed of human brain microvascular endothelial cells (bmecs) grown o ... | 2004 | 15562595 |
| treatment and control of human african trypanosomiasis. | access to treatment is a multi-step process and little progress has been made to improve treatments for sleeping sickness over the past 50 years. the current strategy is based on diagnostic tools developed in the 1960s while available drugs are still the same as those developed in the middle of the last century. strategic opportunities can only be based on two achievements: improved diagnosis and safer drugs. this paper reviews the development of new diagnostic tools and drugs and the opportunit ... | 2004 | 15640711 |
| human african trypanosomiasis: clinical presentation and immune response. | human african trypanosomiasis or sleeping sickness is caused by infection with two subspecies of the tsetse-fly-vectored haemoflagellate parasite trypanosoma brucei. historically, epidemic sleeping sickness has caused massive loss of life, and related animal diseases have had a crucial impact on development in sub-saharan africa. after a period of moderately successful control during the mid-part of the 20th century, sleeping sickness incidence is currently rising, and control is hampered by a c ... | 2004 | 15771682 |
| anaemia in human african trypanosomiasis caused by trypanosoma brucei rhodesiense. | to find out if indeed anaemia is a major sign in human trypanosomiasis caused by trypanosoma brucei rhodensiense. | 2004 | 15715127 |
| antiprotozoal activities of new bicyclo[2.2.2]octan-2-imines and esters of bicyclo[2.2.2]octan-2-ols. | several bicyclo[2.2.2]octan-2-imines and esters of bicyclo[2.2.2]octan-2-ols were prepared. their antitrypanosomal and antiplasmodial activities against trypanosoma brucei rhodesiense (stib 900) and the k1 strain of plasmodium falciparum (resistant to chloroquine and pyrimethamine) were determined using microplate assays. two of the synthesized bicyclo[2.2.2]octan-2-one 4'-phenylthiosemicarbazones showed the highest antitrypanosomal activity (ic(50)<0.3 microm) of the so far prepared 4-amino-6,7 ... | 2004 | 15734294 |
| human african trypanosomiasis. | 2004 | 15751187 | |
| design, synthesis and evaluation of 2,4-diaminoquinazolines as inhibitors of trypanosomal and leishmanial dihydrofolate reductase. | this paper describes the design, synthesis and evaluation of a series of 2,4-diaminoquinazolines as inhibitors of leishmanial and trypanosomal dihydrofolate reductase. compounds were designed by a generating virtual library of compounds and docking them into the enzyme active site. following their synthesis, they were found to be potent and selective inhibitors of leishmanial dihydrofolate reductase. the compounds were also found to have potent activity against trypanosoma brucei rhodesiense, a ... | 2005 | 15755663 |
| characterization of a rab5 homologue in trypanosoma cruzi. | rab proteins are small gtpases involved in exocytic and endocytic pathways of eukaryotic cells, controlling vesicle docking and fusion. rabs show a remarkable specificity in subcellular localization, so they can be used as molecular markers for studying protein trafficking in trypanosoma cruzi, the causal agent of chagas' disease. rab5 is a component of early endosomes. it has been identified in kinetoplastids such as trypanosoma brucei and leishmania donovani. in this work, we describe the char ... | 2005 | 15737633 |
| synthesis of 2-azabicyclo[3.2.2]nonanes from bicyclo[2.2.2]octan-2-ones and their activities against trypanosoma brucei rhodesiense and plasmodium falciparum k1. | new 2-azabicyclo[3.2.2]nonanes were prepared from antiprotozoal bicyclo[2.2.2]octan-2-ones to investigate the influence of the replacement of the rigid bicyclo-octane structure by the more flexible bicyclo-nonane system on the antiplasmodial and antitrypanosomal activity. | 2005 | 16401404 |
| tnf-alpha mediates the development of anaemia in a murine trypanosoma brucei rhodesiense infection, but not the anaemia associated with a murine trypanosoma congolense infection. | development of anaemia in inflammatory diseases is cytokine-mediated. specifically, the levels of tumour necrosis factor-alpha (tnf-alpha), produced by activated macrophages, are correlated with severity of disease and anaemia in infections and chronic disease. in african trypanosomiasis, anaemia develops very early in infection around the time when parasites become detectable in the blood. since the anaemia persists after the first waves of parasitaemia when low numbers of trypanosomes are circ ... | 2005 | 15730385 |
| irreversible inactivation of trypanothione reductase by unsaturated mannich bases: a divinyl ketone as key intermediate. | trypanothione reductase is a flavoenzyme unique to trypanosomatid parasites. here we show that unsaturated mannich bases irreversibly inactivate trypanothione reductase from trypanosoma cruzi, the causative agent of chagas' disease. the inhibitory potency of the compounds strongly increased upon storage of the dmso stock solutions. hplc, nmr, and mass spectrometry data of potential intermediates revealed a divinyl ketone as the active compound inactivating the enzyme. esi- and maldi-tof mass spe ... | 2005 | 16279799 |
| sleeping sickness in uganda: a thin line between two fatal diseases. | to determine, through the use of molecular diagnostic tools, whether the two species of parasite that cause human african trypanosomiasis have become sympatric. | 2005 | 16308383 |
| antitrypanosomal, antileishmanial, and antimalarial activities of quaternary arylalkylammonium 2-amino-4-chlorophenyl phenyl sulfides, a new class of trypanothione reductase inhibitor, and of n-acyl derivatives of 2-amino-4-chlorophenyl phenyl sulfide. | quaternization of the nitrogen atom of 2-amino-4-chlorophenyl phenyl sulfide analogues of chlorpromazine improved inhibition approximately 40-fold (3',4'-dichlorobenzyl-[5-chloro-2-phenylsulfanyl-phenylamino)-propyl]-dimethylammonium chloride inhibited trypanothione reductase from trypanosoma cruzi with a linear competitive ki value of 1.7 +/- 0.2 microm). molecular modelling explained docking orientations and energies by: (i) involvement of the z-site hydrophobic pocket (roughly bounded by f396 ... | 2005 | 16335933 |
| [analysis of molecular profiles among trypanozoon species and subspecies by mge-pcr method]. | to analyze the relationship between genetic variability and evolution among trypanosoma brucei (including t. b. brucei, t. b. rhodesiense and t. b. gambiense), t. evansi and t. equiperdum isolates. | 2005 | 16562478 |
| ambigol c and 2,4-dichlorobenzoic acid, natural products produced by the terrestrial cyanobacterium fischerella ambigua. | the new natural products 3,5-bis(2,4-dichlorophenoxy)-2,6-dichlorophenol (ambigol c, 1), a highly chlorinated aromatic compound, and 2,4-dichlorobenzoic acid (2) were isolated from the terrestrial cyanobacterium fischerella ambigua together with the known compounds ambigol a (3) and tjipanazole d (4). all structures were secured by extensive spectroscopic analysis (1d and 2d nmr, ms, uv, ir). ambigol c has moderate activity against trypanosoma rhodesiense. | 2005 | 15787461 |
| trypanosomes expressing a mosaic variant surface glycoprotein coat escape early detection by the immune system. | host resistance to african trypanosomiasis is partially dependent on an early and strong t-independent b-cell response against the variant surface glycoprotein (vsg) coat expressed by trypanosomes. the repetitive array of surface epitopes displayed by a monotypic surface coat, in which identical vsg molecules are closely packed together in a uniform architectural display, cross-links cognate b-cell receptors and initiates t-independent b-cell activation events. however, this repetitive array of ... | 2005 | 15845470 |
| biphenylquinuclidines as inhibitors of squalene synthase and growth of parasitic protozoa. | in this paper we describe the preparation of some biphenylquinuclidine derivatives and their evaluation as inhibitors of squalene synthase in order to explore their potential in the treatment of the parasitic diseases leishmaniasis and chagas disease. the compounds were screened against recombinant leishmania major squalene synthase and against leishmania mexicana promastigotes, leishmania donovani intracellular amastigotes and trypanosoma cruzi intracellular amastigotes. compounds that inhibite ... | 2005 | 15848765 |
| review article: cerebrospinal fluid in human african trypanosomiasis: a key to diagnosis, therapeutic decision and post-treatment follow-up. | human african trypanosomiasis is a lethal parasitic infection with neurological involvement. examination of the cerebrospinal fluid (csf) plays an essential role in diagnosis, selection of treatment and post-treatment follow-up. this paper reviews clinical presentation, diagnosis and treatment of the disease, with emphasis on csf characteristics and interpretation of the csf results for therapeutic decision and post-treatment follow-up. | 2005 | 15860085 |
| immunization of rabbits with glossina pallidipes tsetse fly midgut proteins: effects on the fly and trypanosome transmission. | proteins isolated from the midgut of glossina pallidipes were used to immunize rabbits and their efficacy as vaccine candidate(s) against the fly, and their potential to block transmission of trypanosoma brucei rhodesiense assessed. two fractions, detergent (det) and aqueous (aq) fractions were separated using a non-ionic detergent (triton x-114) and a series of bioassay experiments carried out using serum obtained from rabbits immunized with either of the two fractions. the mortality rates of t ... | 2005 | 15893620 |
| synthesis and evaluation of the antitrypanosomal and antiplasmodial activities of new 4-aminobicyclo[2.2.2]octane derivatives. | several new 4-amino-6,7-diphenylbicyclo[2.2.2]octane derivatives, methylthiosemicarbazones of bicyclo[2.2.2]octan-2-ones and esters of bicyclo[2.2.2]octan-2-ols were prepared. their antitrypanosomal activities against trypanosoma brucei rhodesiense (stib 900) and their antiplasmodial activity against the k1 strain of plasmodium falciparum (resistant to chloroquine and pyrimethamine) were investigated using microplate assays. in addition to that, the cytotoxicity of the new compounds was determin ... | 2005 | 15913846 |
| ent-dioncophylleine a and related dehydrogenated naphthylisoquinoline alkaloids, the first asian dioncophyllaceae-type alkaloids, from the "new"plant species ancistrocladus benomensis. | three new fully dehydrogenated naphthylisoquinoline alkaloids, the 7,1'-coupled ent-dioncophylleine a (3a), the likewise 7,1'-coupled 5'-o-demethyl-ent-dioncophylleine a (4), and the 7,8'-linked dioncophylleine d (5), have been isolated from the leaves of the recently described malaysian highland liana ancistrocladusbenomensis. all of them lack an oxygen function at c-6; this so-called dioncophyllaceae-type structural subclass had previously been found only in naphthylisoquinoline alkaloids from ... | 2005 | 15921410 |
| leishmanicidal cycloartane-type triterpene glycosides from astragalus oleifolius. | two new cycloartane-type glycosides oleifoliosides a (1) and b (2) were isolated from the lower stem parts of astragalus oleifolius. their structures were identified as 3-o-[beta-xylopyranosyl-(1 --> 2)-alpha-arabinopyranosyl]-6-o-beta-xylopyranosyl-3beta,6alpha,16beta,24(s),25-pentahydroxycycloartane and 3-o-[beta-xylopyranosyl-(1 --> 2)-alpha-arabinopyranosyl]-6-o-beta-glucopyranosyl-3beta,6alpha,16beta,24(s),25-pentahydroxycycloartane, respectively, by means of spectroscopic methods (ir, 1d a ... | 2005 | 15922377 |
| preparation of transition-state analogues of sterol 24-methyl transferase as potential anti-parasitics. | there is an urgent need for new drugs to treat leishmaniasis and chagas disease. one important drug target in these organisms is sterol biosynthesis. in these organisms the main endogenous sterols are ergosta- and stigmata-like compounds in contrast to the situation in mammals, which have cholesterol as the sole sterol. in this paper we discuss the design, synthesis and evaluation of potential transition state analogues of the enzyme delta24(25)-methyltransferase (24-smt). this enzyme is essenti ... | 2005 | 16046134 |
| dicationic near-linear biphenyl benzimidazole derivatives as dna-targeted antiprotozoal agents. | a series of near-linear biphenyl benzimidazole diamidines 5a-h were synthesized from their respective diamidoximes (4a-h), through the bis-o-acetoxyamidoxime, followed by hydrogenation in glacial acetic acid/ethanol in the presence of pd-c. compounds 4a-h were obtained in three steps, starting with the suzuki coupling reaction of the appropriate haloarylcarbonitriles 1a-g or 4-bromo-2-fluorobenzaldehyde with 4-formylphenylboronic acid or 4-cyanophenylboronic acid to form the anticipated 4-formyl ... | 2005 | 16099661 |
| synthesis, dna affinity, and antiprotozoal activity of fused ring dicationic compounds and their prodrugs. | dicationic guanidine, n-alkylguanidine, and reversed amidine derivatives of fused ring systems have been synthesized from their corresponding bis-amines. dna binding studies suggest that the diguanidines and the n-alkyl diguanidines fluorenes bind in the minor groove in a manner similar to that of the previously reported dicationic carbazole derivatives. the diguanidines and the n-alkyl diguanidines showed promising in vitro activity against both trypanosoma brucei rhodesiense and plasmodium fal ... | 2005 | 16107146 |
| design and synthesis of a series of melamine-based nitroheterocycles with activity against trypanosomatid parasites. | the parasites that give rise to human african trypanosomiasis (hat) are auxotrophs for various nutrients from the human host, including purines. they have specialist nucleoside transporters to import these metabolites. in addition to uptake of purine nucleobases and purine nucleosides, one of these transporters, the p2 transporter, can carry melamine derivatives; these derivatives are not substrates for the corresponding mammalian transporters. in this paper, we report the coupling of the melami ... | 2005 | 16107157 |
| expression of alternative oxidase inhibits programmed cell death-like phenomenon in bloodstream form of trypanosoma brucei rhodesiense. | trypanosoma brucei rhodesiense is one of the causative agents of african trypanosomiasis. programmed cell death (pcd) is fundamental in the development, homeostasis and immune mechanisms of multicellular organisms. it has been shown that, other than occurring in multicellular organisms, the pcd phenomenon also takes place in unicellular organisms. in the present study, we have found that under high-density axenic culture conditions, bloodstream form of t. b. rhodesiense depicts a pcd-like phenom ... | 2005 | 16115792 |
| human african trypanosomiasis and human immunodeficiency virus co-infection in western kenya. | to determine possible interaction between infections of trypanosoma brucei rhodesiense sleeping sickness and hiv/aids in western kenya. | 2005 | 16122107 |
| control of sleeping sickness--time to integrate approaches. | 2005 | 16125571 | |
| a burgeoning epidemic of sleeping sickness in uganda. | the epidemic of trypanosoma brucei rhodesiense sleeping sickness in eastern uganda, which began in 1998 as a result of movements of the livestock reservoir of the parasite, has continued to spread. an additional 133 000 people have been put at risk of infection in kaberamaido, another newly affected district. the few resources committed to control interventions in soroti district have failed to contain the epidemic. the high prevalence of the parasite in cattle presents a significant risk for tr ... | 2005 | 16125592 |
| transmissibility of trypanosoma brucei during its development in cattle. | recent outbreaks of trypanosoma brucei rhodesiense sleeping sickness in soroti district of eastern uganda have demonstrated the important role cattle can play as reservoirs of this parasite. to clarify the epidemiological importance of the cattle reservoir, experiments were conducted to determine the ease with which t. brucei is transmitted during the course of its development in friesian cattle. the development of t. brucei in cattle is characterized by an acute phase with high levels of parasi ... | 2005 | 16135189 |
| quantifying the level of under-detection of trypanosoma brucei rhodesiense sleeping sickness cases. | to formally quantify the level of under-detection of trypanosoma brucei rhodesiense sleeping sickness (ss) during an epidemic in uganda, a decision tree (under-detection) model was developed; concurrently, to quantify the subset of undetected cases that sought health care but were not diagnosed, a deterministic (subset) model was developed. the values of the under-detection model parameters were estimated from previously published records of the duration of symptoms prior to presentation and the ... | 2005 | 16135190 |
| dot enzyme-linked immunosorbent assay for more reliable staging of patients with human african trypanosomiasis. | human african trypanosomiasis (hat) or sleeping sickness is a disease characterized by a hemolymphatic stage 1 followed by a meningoencephalitic stage 2 which is fatal without specific treatment. furthermore, due to the toxicity of drugs used to treat stage 2 (mainly melarsoprol) accurate staging is required. actual criteria employed during field surveys are not sensitive enough for precise staging. antineurofilament (anti-nf) and antigalactocerebrosides (anti-galc) antibodies have been identifi ... | 2005 | 16145142 |
| the sra gene: the key to understanding the nature of trypanosoma brucei rhodesiense. | 2005 | 16145931 | |
| deoxyuridine triphosphate nucleotidohydrolase as a potential antiparasitic drug target. | this paper describes a structure-activity study to identify novel, small-molecule inhibitors of the enzyme deoxyuridine 5'-triphosphate nucleotidohydrolase (dutpase) from parasitic protozoa. the successful synthesis of a variety of analogues of dump is described in which the substituents are introduced at the 3'- and 5'-positions, together with variation in the heteroatom at the 5'-position. the compounds were assayed against recombinant plasmodium falciparum and leishmania major enzymes and the ... | 2005 | 16161998 |
| antileishmanial activity, cytotoxicity and qsar analysis of synthetic dihydrobenzofuran lignans and related benzofurans. | a series of synthetic dihydrobenzofuran lignans and related benzofurans were evaluated for their cytotoxicity in a screening panel consisting of various human tumour cell lines, and for their antiprotozoal activity against l. donovani (axenic amastigotes), chloroquine resistant plasmodium falciparum (strain k1), trypanosoma brucei rhodesiense and t. cruzi, and for cytotoxicity on l6 cells. no promising cytotoxicities against human tumour cell lines were observed for newly synthesised compounds, ... | 2005 | 15653333 |
| options for field diagnosis of human african trypanosomiasis. | human african trypanosomiasis (hat) due to trypanosoma brucei gambiense or t. b. rhodesiense remains highly prevalent in several rural areas of sub-saharan africa and is lethal if left untreated. therefore, accurate tools are absolutely required for field diagnosis. for t. b. gambiense hat, highly sensitive tests are available for serological screening but the sensitivity of parasitological confirmatory tests remains insufficient and needs to be improved. screening for t. b. rhodesiense infectio ... | 2005 | 15653823 |
| anti-protozoal and plasmodial fabi enzyme inhibiting metabolites of scrophularia lepidota roots. | the ethanolic root extract of scrophularia lepidota, an endemic plant of the turkish flora, has been investigated for its anti-protozoal and inhibitory effect towards plasmodial enoyl-acp reductase (fabi), a key enzyme of fatty acid biosynthesis in plasmodium falciparum. chromatographic separation of the extract yielded 10 iridoids (1-10), two of which are new, and a known phenylethanoid glycoside (11). the structures of the new compounds were determined as 3,4-dihydro-methylcatalpol (8) and 6-o ... | 2005 | 15680992 |
| using remote sensing and geographic information systems to identify villages at high risk for rhodesiense sleeping sickness in uganda. | geographic information systems (gis) and remote sensing were used to identify villages at high risk for sleeping sickness, as defined by reported incidence. landsat enhanced thematic mapper (etm) satellite data were classified to obtain a map of land cover, and the normalised difference vegetation index (ndvi) and landsat band 5 were derived as unclassified measures of vegetation density and soil moisture, respectively. gis functions were used to determine the areas of land cover types and mean ... | 2006 | 16246384 |
| solid phase synthesis and antiprotozoal evaluation of di- and trisubstituted 5'-carboxamidoadenosine analogues. | the rapid increase of resistance to drugs commonly used in the treatment of tropical diseases such as malaria and african sleeping sickness calls for the prompt development of new safe and efficacious drugs. the pathogenic protozoan parasites lack the capability of synthesising purines de novo and they take up preformed purines from their host through various transmembrane transporters. adenosine derivatives constitute a class of potential therapeutics due to their selective internalisation by t ... | 2006 | 16249090 |
| antitrypanosomal and antileishmanial activities of flavonoids and their analogues: in vitro, in vivo, structure-activity relationship, and quantitative structure-activity relationship studies. | trypanosomiasis and leishmaniasis are important parasitic diseases affecting millions of people in africa, asia, and south america. in a previous study, we identified several flavonoid glycosides as antiprotozoal principles from a turkish plant. here we surveyed a large set of flavonoid aglycones and glycosides, as well as a panel of other related compounds of phenolic and phenylpropanoid nature, for their in vitro activities against trypanosoma brucei rhodesiense, trypanosoma cruzi, and leishma ... | 2006 | 16569852 |
| harbouring in the brain: a focus on immune evasion mechanisms and their deleterious effects in malaria and human african trypanosomiasis. | malaria and human african trypanosomiasis represent the two major tropical vector-transmitted protozoan infections, displaying different prevalence and epidemiological patterns. death occurs mainly due to neurological complications which are initiated at the blood-brain barrier level. adapted host-immune responses present differences but also similarities in blood-brain barrier/parasite interactions for these diseases: these are the focus of this review. we describe and compare parasite evasion ... | 2006 | 16600243 |
| experimental therapy of african trypanosomiasis with a nanobody-conjugated human trypanolytic factor. | high systemic drug toxicity and increasing prevalence of drug resistance hampers efficient treatment of human african trypanosomiasis (hat). hence, development of new highly specific trypanocidal drugs is necessary. normal human serum (nhs) contains apolipoprotein l-i (apol-i), which lyses african trypanosomes except resistant forms such as trypanosoma brucei rhodesiense. t. b. rhodesiense expresses the apol-i-neutralizing serum resistance-associated (sra) protein, endowing this parasite with th ... | 2006 | 16604085 |
| human african trypanosomiasis: in and out of africa. | 2006 | 16606904 | |
| lethal african trypanosomiasis in a traveler: mri and neuropathology. | the authors report a case of human african trypanosomiasis with cns involvement caused by trypanosoma brucei rhodesiense in a 52-year-old woman, which relapsed after melarsoprol treatment. after a second regimen, she developed a severe toxic polyneuropathy, progressing to coma and eventually death. mri revealed rapidly progressive multiple white matter lesions as well as damage of the central gray matter and cortex. the autopsy results confirmed the diagnosis of human african trypanosomiasis. | 2006 | 16606924 |
| trypanosoma evansi: genetic variability detected using amplified restriction fragment length polymorphism (aflp) and random amplified polymorphic dna (rapd) analysis of kenyan isolates. | we compared two methods to generate polymorphic markers to investigate the population genetics of trypanosoma evansi; random amplified polymorphic dna (rapd) and amplified restriction fragment length polymorphism (aflp) analyses. aflp accessed many more polymorphisms than rapd. cluster analysis of the aflp data showed that 12 t.evansi isolates were very similar ('type a') whereas 2 isolates differed substantially ('type b'). type a isolates have been generally regarded as genetically identical b ... | 2006 | 16624308 |
| the rise and fall of sleeping sickness. | 2006 | 16650633 | |
| application of multicomponent reactions to antimalarial drug discovery. part 2: new antiplasmodial and antitrypanosomal 4-aminoquinoline gamma- and delta-lactams via a 'catch and release' protocol. | a parallel synthesis of a new series of 4-aminoquinoline gamma- and delta-lactams synthesized via the ugi 3-component 4-centre multicomponent reaction is described. the basicity of the quinoline nitrogen was exploited in the purification of compounds via a 'catch and release' protocol. yields ranging from 60% to 77% and purities as high as 96% were obtained. compound 29, the most active against a chloroquine-resistant w2 strain of plasmodium falciparum with an ic(50) of 0.096 microm, also inhibi ... | 2006 | 16690319 |
| turkish freshwater and marine macrophyte extracts show in vitro antiprotozoal activity and inhibit fabi, a key enzyme of plasmodium falciparum fatty acid biosynthesis. | the ethanolic extracts of a number of turkish freshwater macrophytes (potamogeton perfoliatus, ranunculus tricophyllus and cladophora glomerata) and marine macroalgae (dictyota dichotoma, halopteris scoparia, posidonia oceanica, scinaia furcellata, sargassum natans and ulva lactuca) were assayed for their in vitro antiprotozoal activity. trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani and plasmodium falciparum were used as test organisms. the cytotoxicity of the extracts w ... | 2006 | 16697632 |
| spatial analysis of sleeping sickness, southeastern uganda, 1970-2003. | sleeping sickness re-emerged in southeastern uganda in the 1970s and remains a public health problem. it has continued to spread north into new districts, and gaps remain in the understanding of the causes of its spread and distribution. we report the distribution and magnitude of sleeping sickness in southeastern uganda from 1970 to 2003. data were collected from records of the ugandan ministry of health, individual sleeping sickness treatment centers, and interviews with public health official ... | 2006 | 16704843 |
| the trypanolytic factor of human serum. | african trypanosomes (the prototype of which is trypanosoma brucei brucei) are protozoan parasites that infect a wide range of mammals. human blood, unlike the blood of other mammals, has efficient trypanolytic activity, and this needs to be counteracted by these parasites. resistance to this activity has arisen in two subspecies of trypanosoma brucei - trypanosoma brucei rhodesiense and trypanosoma brucei gambiense - allowing these parasites to infect humans, and this results in sleeping sickne ... | 2006 | 16710327 |
| antiplasmodial and antitrypanosomal activity of new esters and ethers of 4-dialkylaminobicyclo[2.2.2]octan-2-ols. | only three drugs are available for the treatment of east african trypanosomiasis. patients suffer from painful application, severe side effects and increasing resistance against these drugs. malaria tropica kills more than 2 million people every year mainly due to growing drug resistance. 4-dialkylaminobicyclo[2.2.2]octan-2-ols and some of their esters have shown activity against both the causative organisms, trypanosoma brucei rhodesiense and plasmodium falciparum. ethers and new esters with ma ... | 2006 | 16713699 |
| triterpenic acids and flavonoids from satureja parvifolia. evaluation of their antiprotozoal activity. | bioassay-guided fractionation of a satureja parvifolia meoh extract led to the isolation of eriodictyol, luteolin and ursolic and oleanolic acids as its active components against plasmodium falciparum k1. this is the first time these compounds are reported as constituents of s. parvifolia. ursolic acid showed an ic50 of 4.9 microg/ml, luteolin 6.4 microg/ml, oleanolic acid 9.3 microg/ml and eriodictyol 17.2 microg/ml. antiplasmodial activity of eriodictyol and luteolin is reported here for the f ... | 2006 | 16729575 |
| efficacy of dipalmitoylphosphatidylcholine liposome against african trypanosomes. | we demonstrate here that dipalmitoylphosphatidylcholine (dppc) liposome has an antitrypanosomal effect, especially against the bloodstream forms (bsfs) of african trypanosomes (trypanosoma congolense, t. brucei rhodesiense, and t. brucei brucei). the dppc liposome significantly decreased the in vitro percentage of viable and motile bsf african trypanosomes but only marginally reduced the percentage of viable and motile procyclic form (pcf) of trypanosomes. the dppc liposome absorption was much m ... | 2006 | 16729700 |
| synthesis of new esters and oximes with 4-aminobicyclo[2.2.2]octane structure and evaluation of their antitrypanosomal and antiplasmodial activities. | new 4-amino-6,7-diphenylbicyclo[2.2.2]octane derivatives, esters of bicyclo[2.2.2]octan-2-ols and o-methyl oximes of bicyclo[2.2.2]octan-2-ones were synthesised. their activities against trypanosoma brucei rhodesiense (stib 900) and their activity against the k1 strain of plasmodium falciparum (resistant to chloroquine and pyrimethamine) were determined by use of microplate assays. the cytotoxicity was assessed using l6 cells. the antiprotozoal activities of the new compounds are compared with t ... | 2006 | 16730393 |
| human african trypanosomiasis: epidemiology and control. | human african trypanosomiasis (hat), or sleeping sickness, describes not one but two discrete diseases: that caused by trypanosoma brucei rhodesiense and that caused by t. b. gambiense. the gambian form is currently a major public health problem over vast areas of central and western africa, while the zoonotic, rhodesian form continues to present a serious health risk in eastern and southern africa. the two parasites cause distinct clinical manifestations, and there are significant differences i ... | 2006 | 16735165 |
| dna binding affinity of bisguanidine and bis(2-aminoimidazoline) derivatives with in vivo antitrypanosomal activity. | a new antitrypanosomal hit compound that cures an acute (stib 900) mouse model of trypanosoma brucei rhodesiense trypanosomiasis is described. this bis(2-aminoimidazolinium) dicationic compound proved to be an excellent dna minor groove binder, suggesting a possible mechanism for its trypanocidal activity. from these studies, the 4,4'-diaminodiphenylamine skeleton emerged as a good scaffold for antitrypanosomal drugs. | 2006 | 16759117 |
| overcoming resistance with designer immunotoxins. | normal human serum contains apolipoprotein l-i (apol-i), which lyses african trypanaosomes. resistant forms, such as trypanosoma brucei rhodesiense express apol-i-neutralising serum resistance-associated protein, which enables this parasite to infect humans and cause human african trypanosomiasis. this paper describes the construction of a mutant apol-i conjugated to a nanobody that targets the variant surface glycoprotein of trypanosomes. treatment with this engineered immunotoxin has resulted ... | 2006 | 16805725 |
| human african trypanosomiasis: connecting parasite and host genetics. | in west and central africa, the protozoan parasite trypanosoma brucei (t. b.) gambiense causes a chronic form of human african trypanosomiasis (hat) that might last several years, whereas t. b. rhodesiense refers to an acute form in east africa that lasts weeks to months. without treatment, both forms can cause death. diagnosis relies on detecting parasites in blood, lymph or cerebrospinal fluid. hat was no longer considered a public health problem in the 1960s, but it returned to alarming level ... | 2006 | 16837245 |
| signal transduction, gene transcription, and cytokine production triggered in macrophages by exposure to trypanosome dna. | activation of a type i cytokine response is important for early resistance to infection with trypanosoma brucei rhodesiense, the extracellular protozoan parasite that causes african sleeping sickness. the work presented here demonstrates that trypanosome dna activates macrophages to produce factors that may contribute to this response. initial results demonstrated that t. brucei rhodesiense dna was present in the plasma of c57bl/6 and c57bl/6-scid mice following infection. subsequently, the effe ... | 2006 | 16861639 |
| glossina fuscipes fuscipes in the trypanosomiasis endemic areas of south eastern uganda: apparent density, trypanosome infection rates and host feeding preferences. | a study was undertaken in three districts in south eastern uganda endemic for human and animal trypanosomiasis, to investigate the status of the vector tsetse fly population. apparent density (ad) of tsetse was between 2 and 21 flies/trap/day across the three districts, with glossinia fuscipes fuscipes identified as the predominant species. trypanosomes were observed in g.f. fuscipes with an infection rate, as determined by microscopy, of 1.55% across the three studied areas. however, trypanosom ... | 2006 | 16870129 |
| new azasterols against trypanosoma brucei: role of 24-sterol methyltransferase in inhibitor action. | a series of azasterol derivatives, designed as potential inhibitors of the delta(24)-sterol methyltransferase enzyme (24-smt), were synthesized and evaluated for their activities against parasitic protozoa. values in the nanomolar range were obtained for 50% effective dose against the trypanosoma brucei subsp. rhodesiense bloodstream form cultured in vitro. in order to investigate the mode of action, trypanosoma brucei subsp. brucei 24-smt was cloned and overexpressed and compounds were assayed ... | 2006 | 16870747 |
| antiprotozoal activities of new bis-chlorophenyl derivatives of bicyclic octanes and aza-nonanes. | the in vitro activity of newly synthesized bis-(chlorophenyl)-azabicyclo[3.2.2]nonanes and bis-(chlorophenyl)-bicyclo[2.2.2]octanes against plasmodium falciparum k(1) (resistant to chloroquine and pyrimethamine) and trypanosoma brucei rhodesiense was investigated. especially the bis-(chlorophenyl)-azabicyclo[3.2.2]nonanes exhibit promising antitrypanosomal activity and were tested in vivo against trypanosoma brucei brucei featuring moderate activities. | 2006 | 16889962 |
| dicationic dna-targeted antiprotozoal agents: naphthalene replacement of benzimidazole. | a series of naphthalene analogues of highly active benzimidazole diamidines were synthesized using sequential stille and suzuki coupling reactions for preparation of the bis-nitrile intermediates. all of the diamidines showed strong dna affinities as judged by high deltatm values with poly(da-dt). the dicationic compounds were quite active in vitro versus trypanosoma brucei rhodesiense (t. b. r.) exhibiting ic50 values ranging from 4 to 98 nm. these compounds were also active versus plasmodium f ... | 2006 | 16889966 |
| in vitro generation of human high-density-lipoprotein-resistant trypanosoma brucei brucei. | the host range of african trypanosomes is influenced by innate protective molecules in the blood of primates. a subfraction of human high-density lipoprotein (hdl) containing apolipoprotein a-i, apolipoprotein l-i, and haptoglobin-related protein is toxic to trypanosoma brucei brucei but not the human sleeping sickness parasite trypanosoma brucei rhodesiense. it is thought that t. b. rhodesiense evolved from a t. b. brucei-like ancestor and expresses a defense protein that ablates the antitrypan ... | 2006 | 16896212 |
| il-10 is up regulated in early and transitional stages in vervet monkeys experimentally infected with trypanosoma brucei rhodesiense. | il-10 has been suggested as a possible parameter for human african trypanosomiasis stage determination. however, conclusive experimental studies have not been carried out to evaluate this, which is a prerequisite before a potential test can be validated in humans for diagnostic purposes. we used the vervet monkey model of trypanosomiasis to scrutinize il-10 in blood and cerebrospinal fluid (csf). five adult males were experimentally infected with t. b. rhodesiense. the infected animals became an ... | 2006 | 16901747 |
| synthesis, dna affinity, and antiprotozoal activity of linear dications: terphenyl diamidines and analogues. | diamidines 10a-g and 18a,b were obtained from dinitriles 9a-g and 15a,b by treatment with lithium trimethylsilylamide or upon hydrogenation of bis-o-acetoxyamidoximes. dinitriles 9a-g were prepared via suzuki reactions between arylboronic acids and arylnitriles. potential prodrugs 12a-f and 17 were prepared via methylation of the diamidoximes 11a-f and 16a. significant dna affinities for rigid-rod molecules were observed. compounds 10a, 10b, 10d, 18a, and 18b show ic50 values of 5 nm or less aga ... | 2006 | 16913722 |
| blood-brain barrier traversal by african trypanosomes requires calcium signaling induced by parasite cysteine protease. | in this study we investigated why bloodstream forms of trypanosoma brucei gambiense cross human brain microvascular endothelial cells (bmecs), a human blood-brain barrier (bbb) model system, at much greater efficiency than do t. b. brucei. after noting that t. b. gambiense displayed higher levels of cathepsin l-like cysteine proteases, we investigated whether these enzymes contribute to parasite crossing. first, we found that t. b. gambiense crossing of human bmecs was abrogated by n-methylpiper ... | 2006 | 16998589 |
| evaluation of azasterols as anti-parasitics. | in this article, the design and synthesis of some novel azasterols is described, followed by their evaluation against trypanosoma brucei rhodesiense, t. cruzi, leishmania donovani, and plasmodium falciparum, the causative agents of human african trypanosomiasis, chagas disease, leishmaniasis, and malaria, respectively. some of the compounds showed anti-parasitic activity. in particular, a number of compounds appeared to very potently inhibit the growth of the blood stream form t. b. rhodesiense, ... | 2006 | 17004723 |
| in vitro antiprotozoal activity of the lipophilic extracts of different parts of turkish pistacia vera l. | thirteen lipophilic extracts prepared with n-hexane from various parts of pistacia vera l. tree (anacardiaceae) growing in turkey were screened for their in vitro activity against four parasitic protozoa, trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani and plasmodium falciparum. melarsoprol, benznidazole, miltefosine, artemisinin and chloroquine were used as reference drugs. the cytotoxic potentials of the extracts on rat skeletal myoblast (l6) cells were also assessed and ... | 2006 | 17085297 |
| lipid metabolism: an apolipoprotein-derived weapon combating trypanosoma infection. | 2006 | 17095915 | |
| novel inhibitors of the trypanosome alternative oxidase inhibit trypanosoma brucei brucei growth and respiration. | african trypanosomiasis is a deadly disease for which few chemotherapeutic options are available. the causative agents, trypanosoma brucei rhodesiense and t. b. gambiense, utilize a non-cytochrome, alternative oxidase (aox) for their cellular respiration. the absence of this enzyme in mammalian cells makes it a logical target for therapeutic agents. we designed three novel compounds, acb41, acd15, and acd16, and investigated their effects on trypanosome alternative oxidase (tao) enzymatic activi ... | 2006 | 17126803 |
| detection of t.b. rhodesiense trypanosomes in humans and domestic animals in south east uganda by amplification of serum resistance-associated gene. | the human serum resistance-associated (sra) gene was identified in 28 (80%) of the 35 t.b. rhodesiense trypanosomes from parasitologically confirmed sleeping sickness cases, using the primers designed by radwanska and in 27 (77.1%) of the same 35 t.b. rhodesiense trypanosomes using the primers designed by gibson. however, about 20% of the 35 t.b. rhodesiense trypanosomes could not be detected by sra-polymerase chain reaction (pcr) even when an aliquot of the first pcr was used in the second pcr, ... | 2006 | 17135530 |
| trypanocidal activity of methylene blue. evidence for in vitro efficacy and in vivo failure. | human african trypanosomiasis remains a difficult health problem to treat because of the few compounds available nowadays and their toxicity. the disease also affects animals and is therefore responsible for economic difficulties and zoonotic risks. there is an urgent need to develop new drugs for treatment of african trypanosomiasis. methylene blue is a safe and easy-to-use drug employed in human therapy. it is also known to have antimalarial activity. in this study, methylene blue trypanocidal ... | 2006 | 16340192 |
| intrathecal cytokine responses in trypanosoma brucei rhodesiense sleeping sickness patients. | intrathecal cytokine levels and blood-cerebrospinal fluid (csf) barrier function were studied in 91 trypanosoma brucei rhodesiense-infected patients. the csf concentration of the cellular immune activation marker neopterin and the cytokines il-6 and il-10 were increased over control and post-treatment levels in all patients, with maximal levels observed in late-stage (meningoencephalitic) individuals. analysis of csf/serum concentration quotients indicated that il-10 and neopterin were derived f ... | 2006 | 16343570 |
| alkyl-linked bis-thtt derivatives as potent in vitro trypanocidal agents. | the effect of several alkyl-linked bis tetrahydro-(2h)-1,3,5-thiadiazine-2-thione (bis-thtt) on leishmania donovani, trypanosoma brucei rhodesiense, and plasmodium falciparum is reported. most of the compounds exhibited a potent activity against the three parasitic strains but the best in vitro activity profiles were found against t. b. rhodesiense with ic(50) values ranging between 0.3 and 4 microm for the most active compounds. | 2006 | 16343898 |
| central point sampling from cattle in livestock markets in areas of human sleeping sickness. | we present the results of a study to determine the value of central point sampling in cattle markets as a means of estimating the trypanosomiasis (t. brucei s.l.) prevalence in the surrounding landscape in uganda. we find that in the epidemic area studied, central point sampling is a good predictor of prevalence in surrounding villages, but not in endemic areas. we also find that animals infected with trypanosomiasis are more likely to be brought for sale in livestock markets in endemic areas; w ... | 2006 | 16387279 |
| serum resistance-associated protein blocks lysosomal targeting of trypanosome lytic factor in trypanosoma brucei. | trypanosoma brucei brucei is the causative agent of nagana in cattle and can infect a wide range of mammals but is unable to infect humans because it is susceptible to the innate cytotoxic activity of normal human serum. a minor subfraction of human high-density lipoprotein (hdl) containing apolipoprotein a-i (apoa-i), apolipoprotein l-i (apol-i), and haptoglobin-related protein (hpr) provides this innate protection against t. b. brucei infection. this hdl subfraction, called trypanosome lytic f ... | 2006 | 16400175 |
| african trypanosomiasis in a british soldier. | human african trypanosomiasis (sleeping sickness) is a parasitic infection transmitted by day-biting tsetse flies. the diagnostic gold standard is microscopy of blood, lymph node aspirates or csf. the disease is invariably fatal, if not treated. there are over 300 000 new cases of sleeping sickness each year, and approximately 100,000 deaths. | 2006 | 17295013 |
| comparative antiplasmodial, leishmanicidal and antitrypanosomal activities of several biflavonoids. | the antiplasmodial, leishmanicidal and antitrypanosomal activities of eight natural biflavonoids were estimated in vitro on a chloroquine-resistant strain of plasmodium falciparum, axenically grown leishmania donovani amastigotes and trypanosoma cruzi trypomastigotes and trypanosoma brucei rhodesiense bloodstream forms. lanaroflavone showed the highest antiplasmodial activity (ic(50) = 0.48 microm), isoginkgetin was the most active leishmanicidal compound (ic(50) = 1.9 microm), whereas ginkgetin ... | 2006 | 16428025 |
| 3d qsar on a library of heterocyclic diamidine derivatives with antiparasitic activity. | african trypanosomes, trypanosoma brucei rhodesiense (tbr) and trypanosoma brucei gambiense (tbg), affect hundreds of thousands of lives in tropical regions of the world. the toxicity of the diamidine pentamidine, an effective drug against tbg, necessitates the design of better drugs. an orally effective prodrug of the diamidine, furamidine (db75), presently scheduled for phase iii clinical trials, has excellent activity against tbg with toxicity lower than that of pentamidine. as part of an eff ... | 2006 | 16442293 |
| drug-resistance of trypanosoma b. rhodesiense isolates from tanzania. | to determine the drug resistance of trypanosoma brucei rhodesiense strains isolated from sleeping sickness patients in tanzania. | 2006 | 16451338 |
| crisis, what crisis? control of rhodesian sleeping sickness. | there is an urgent need for cost-effective strategies for the sustainable control of trypanosoma brucei rhodesiense (rhodesian) sleeping sickness, which is a fatal zoonotic disease that has caused devastating epidemics during the past century. sleeping sickness continues to be controlled by crisis management, using active case detection, treatment and vector control - activities that occur only during major epidemics; during the intervening periods, farmers and communities must fend for themselv ... | 2006 | 16458071 |
| antituberculotic and antiprotozoal activities of primin, a natural benzoquinone: in vitro and in vivo studies. | primin (=2-methoxy-6-pentylcyclohexa-2,5-diene-1,4-dione), a natural benzoquinone synthesized in our laboratory, was investigated for its in vitro antiprotozoal, antimycobacterial, and cytotoxic potential. primin showed very potent activity against trypanosoma brucei rhodesiense (ic50 0.144 microm) and leishmania donovani (ic50 0.711 microm), and revealed low cytotoxicity (ic50 15.4 microm) on mammalian cells. only moderate inhibitory activity was observed against mycobacterium tuberculosis, try ... | 2006 | 17193236 |
| antitrypanosomal cycloartane glycosides from astragalus baibutensis. | baibutoside (5), a new cycloartane-type triterpene glycoside, has been isolated from the roots of astragalus baibutensis along with four known glycosides, acetylastragaloside i (1), and astragalosides i, ii, and iv (2-4, resp.). the structure elucidation of the compounds were achieved by a combination of one- and two-dimensional nmr techniques (dqf-cosy, hsqc, hmbc, and roesy), and mass spectrometry (esi-ms), where all the compounds were shown to have cycloastragenol (=(20r,24s)-3beta,6alpha,16b ... | 2006 | 17193323 |
| african trypanosomiasis. | trypanosomiasis remains one of the most serious constraints to economic development in sub-saharan africa and, as a consequence, related research has been subject to strong social and political as well as scientific influences. the epidemics of sleeping sickness that occurred at the turn of the 20th century focussed research efforts on what became known as 'the colonial disease'. this focus is thought to have produced 'vertical' health services aimed at this one disease, while neglecting other i ... | 2006 | 17227648 |
| limonoid orthoacetates and antiprotozoal compounds from the roots of pseudocedrela kotschyi. | the dicholoromethane extract of pseudocedrela kotschyi root demonstrated marked antileishmanial properties in preliminary screening of extracts from 21 species commonly used in malian traditional medicine. phytochemical investigation of the active extract yielded three novel phragmalin-type limonoid orthoacetates (1-3), named kotschyins a-c, and the known compounds 7-deacetylgedunin (4) and 7-deacetyl-7-oxogedunin (5). the structures of 1-3 were elucidated by analytical methods including 1d- and ... | 2007 | 17253841 |
| human african trypanosomiasis: diagnosis, relapse and survival after severe melarsoprol-induced encephalopathy. | we describe a case of human african trypanosomiasis with a number of unusual features. the clinical presentation was subacute, but the infection was shown to be due to trypanosoma brucei rhodesiense. the infection relapsed twice following treatment and the patient developed a melarsoprol-associated encephalopathy. magnetic resonance imaging (mri) findings were suggestive of microhaemorrhages, well described in autopsy studies of encephalopathy but never before shown on mri. the patient survived ... | 2007 | 17270227 |
| african trypanosomiasis in a british soldier. | sleeping sickness (human african trypanosomiasis) is a parasitic infection transmitted by day-biting tsetse flies. the diagnostic standard is microscopy of blood, lymph node aspirates, or cerebrospinal fluid. the disease is invariably fatal if not treated. there are >300,000 new cases of sleeping sickness each year and approximately 100,000 deaths. | 2007 | 17691692 |
| discovery of 2-iminobenzimidazoles as a new class of trypanothione reductase inhibitor by high-throughput screening. | a high-throughput screening campaign of a library of 100,000 lead-like compounds identified 2-iminobenzimidazoles as a novel class of trypanothione reductase inhibitors. these 2-iminobenzimidazoles display potent trypanocidal activity against trypanosoma brucei rhodesiense, do not inhibit closely related human glutathione reductase and have low cytotoxicity against mammalian cells. | 2007 | 17194585 |
| combination therapy for sleeping sickness: a wake-up call. | 2007 | 17205466 | |
| 2,n6-disubstituted adenosine analogs with antitrypanosomal and antimalarial activities. | a library of 2,n(6)-disubstituted adenosine analogs was synthesized and the analogs were tested for their antiprotozoal activities. it was found that 2-methoxy and 2-histamino and n(6)-m-iodobenzyl substitutions generally produced analogs with low levels of antiprotozoal activity. the best antiplasmodial activity was achieved with large aromatic substitutions, such as n(6)-2,2-diphenylethyl and naphthylmethyl, which could indicate a mechanism of action through aromatic stacking with heme in the ... | 2007 | 17698622 |
| occurrence of multiple drug resistance in trypanosoma brucei rhodesiense isolated from sleeping sickness patients. | the occurrence of cross-resistance among melarsoprol-resistant trypanosoma brucei rhodesiense isolates was investigated in this study. the isolates, t. b. rhodesiense ketri 237, 2538, 1992, 2709, 2694 and 3530, had been obtained from sleeping sickness patients in kenya and uganda between 1960 and 1985. five groups consisting of six mice each were inoculated intraperitoneally with 10(5) parasites of each isolate, and 24 h later treated with either melarsoprol, homidium chloride, diminazene acetur ... | 2007 | 17708149 |
| in vitro and in vivo evaluation of the antitrypanosomal activity of fractions of holarrhena africana. | the aqueous extract of young leaves of holarrhena africana, a plant used in the nigerian traditional medicine, exhibited good activity against trypanosoma brucei spp. the extract was fractionated and eight fractions were obtained. one fraction designated as haf(5) showed in vitro activity against trypanosoma brucei rhodesiense with an ic(50) value of 0.785 microg/mg and no overt cytotoxicity against l-6 cells. fraction haf(5) was tested in vivo at two doses and found to exhibit in vivo efficacy ... | 2007 | 17728085 |
| trypanocidal activity of piperazine-linked bisbenzamidines and bisbenzamidoxime, an orally active prodrug. | a series of 32 piperazine-linked bisbenzamidines (and related analogues) were analysed for their in vitro and in vivo trypanocidal activity against a drug-sensitive strain of trypanosoma brucei brucei and a drug-resistant strain of trypanosoma brucei rhodesiense. the compounds showed similar potencies against both strains. the most potent compounds were bisbenzamidines substituted at the amidinium nitrogens with a linear pentyl group (8, inhibitory concentration for 50% (ic(50))=1.7-3.0 nm) or c ... | 2007 | 17920820 |