Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
|---|
| synthesis and biological evaluation of pyrazolylnaphthoquinones as new potential antiprotozoal and cytotoxic agents. | the importance of american trypanosomiasis (chagas' disease) in human pathology is widely known. the prognosis of this disease is poor and the choice of effective medicines limited, thus study of new drugs is absolutely necessary. in this work, the activities of three new pyrazolylnaphthoquinones, heterocyclic naphthoquinones bearing 3-aminopyrazole rings, were evaluated on trypanosoma cruzi, the etiological agent of chagas' disease. these activities were compared with those of three 5-aminoisox ... | 2003 | 12512078 |
| ancistrolikokine d, a 5,8'-coupled naphthylisoquinoline alkaloid, and related natural products from ancistrocladus likoko. | a new naphthylisoquinoline alkaloid, ancistrolikokine d, and the likewise 5,8'-coupled alkaloid ancistroealaine a, as well as two further, biosynthetically related, but nitrogen-free natural products, ancistronaphthoic acid b and cis-isoshinanolone, have been isolated from ancistrocladus likoko j. leacute;onard (ancistrocladaceae). the 5,8'-coupling of the new alkaloids and of the alkaloids isolated earlier hints at a close phylogenetic relationship of a. likoko to other central african ancistro ... | 2003 | 12560038 |
| the origin of the serum resistance associated (sra) gene and a model of the structure of the sra polypeptide from trypanosoma brucei rhodesiense. | 2003 | 12615339 | |
| trypanocidal activity of conformationally restricted pentamidine congeners. | a series of conformationally restricted congeners of pentamidine in which the flexible pentyl bridge of pentamidine was replaced by trans-1,2-bismethylenecyclopropyl, phenyl, pyridinyl, piperazinyl, homopiperazinyl, and piperidinyl groups were synthesized. the compounds were evaluated for trypanocidal activity in vitro and in vivo against one drug-sensitive and three drug-resistant trypanosome isolates. the dna binding affinity of the compounds was also studied using calf thymus dna and poly(da- ... | 2003 | 12620080 |
| apolipoprotein l-i is the trypanosome lytic factor of human serum. | human sleeping sickness in east africa is caused by the parasite trypanosoma brucei rhodesiense. the basis of this pathology is the resistance of these parasites to lysis by normal human serum (nhs). resistance to nhs is conferred by a gene that encodes a truncated form of the variant surface glycoprotein termed serum resistance associated protein (sra). we show that sra is a lysosomal protein, and that the amino-terminal alpha-helix of sra is responsible for resistance to nhs. this domain inter ... | 2003 | 12621437 |
| treatment perspectives for human african trypanosomiasis. | human african trypanosomiasis (hat), or sleeping sickness, is currently on the rise. hat develops in two stages, the first involving the hemolymphatic system, and the second, the neurological system. left untreated, hat is invariably fatal. there have been no therapeutic advances in more than 40 years. stage 1 can be treated with pentamidine and suramin, but stage 2 can only be treated with melarsoprol, a toxic arsenic derivative that has a 2-12% incidence of fatal side-effects (encephalopathy). ... | 2003 | 12667227 |
| synthesis and in vitro anti-protozoal activity of a series of benzotropolone derivatives incorporating endocyclic hydrazines. | the preparation and evaluation as potential anti-protozoal agents of molecules bearing an endocyclic hydrazine moiety is presented. the synthetic route to this new series of compounds is straightforward, involving a hetero diels-alder reaction between different benzotropolone esters and diethyl azodicarboxylate (dead). while they show limited or no in vitro activity against leishmania donovani, plasmodium falciparum and trypanosoma brucei rhodesiense, several of the compounds have activities aga ... | 2003 | 14642327 |
| drug transport and drug resistance in african trypanosomes. | drug resistance in african trypanosomes has been studied for almost a hundred years. beginning with paul ehrlich's work that led to the chemoreceptor hypothesis, reduction of net drug uptake has emerged as the most frequent cause of resistance. this review, therefore, focuses on trypanosomal drug transporter genes. tbat1 encodes purine permease p2, which mediates influx of melarsoprol and diamidines. disruption of tbat1 in trypanosoma brucei reduced sensitivity to these trypanocides. tbmrpa enco ... | 2003 | 14643298 |
| arsenicals (melarsoprol), pentamidine and suramin in the treatment of human african trypanosomiasis. | human african trypanosomiasis (hat), otherwise known as sleeping sickness, has remained a disease with no effective treatment. recent progress in hat research suggests that a vaccine against the disease is far from being successful. also the emergence of drug-resistant trypanosomes makes further work in this area imperative. so far the treatment for the early stage of hat involves the drugs pentamidine and suramin which have been very successful. in the second stage of the disease, during which ... | 2003 | 12743807 |
| the human serum resistance associated gene is ubiquitous and conserved in trypanosoma brucei rhodesiense throughout east africa. | the human serum resistance associated (sra) gene isolated from a ugandan strain of trypanosoma brucei rhodesiense has been shown to be capable by itself of conferring the trait of human infectivity on t.b. brucei by transfection. this gene has also been identified in several other isolates of t.b. rhodesiense, but not in the other human pathogenic trypanosome in africa, t.b. gambiense, casting doubt on its ubiquity and function. here, we show that this gene occurs in t.b. rhodesiense from sleepi ... | 2002 | 12798017 |
| selective pressure can influence the resistance of trypanosoma congolense to normal human serum. | resistance and sensitivity to normal human serum (nhs) of trypanosoma congolense, a parasite believed to cause disease in animals only, were investigated in vivo as well as in vitro. our results indicate that like trypanosoma brucei, t. congolense can be grouped into three different phenotypes according to its resistance to nhs. some strains are completely resistant to nhs, like trypanosoma brucei gambiense and the resistant form of trypanosoma brucei rhodesiense. other strains show a very low d ... | 2002 | 12706740 |
| the serum resistance-associated gene as a diagnostic tool for the detection of trypanosoma brucei rhodesiense. | in the search for new diagnostic methods that would distinguish trypanosoma brucei rhodesiense from t. b. brucei and t. b. gambiense, we have developed two polymerase chain reaction (pcr) primer sets. the first primer set was derived from the serum resistance-associated (sra) gene of t. b. rhodesiense that confers resistance to lysis by normal human serum (nhs). the specificity of the sra-based pcr was tested on 97 different trypanosome populations originating from various taxonomic groups, host ... | 2002 | 12518862 |
| [three patients with african sleeping sickness following a visit to tanzania]. | three dutch tourists, a man aged 57 and two women aged 55 en 52 years, acquired african trypanosomiasis in the national parks of tanzania. two, without central nervous system involvement, were cured after treatment in the netherlands, albeit one after having suffered a relapse. in the third patient, involvement of the central nervous system was diagnosed in africa and she was treated with melarsoprol. after an apparently uneventful recovery she was readmitted with cerebral complaints and symptom ... | 2002 | 12532670 |
| epithelial innate immunity. a novel antimicrobial peptide with antiparasitic activity in the blood-sucking insect stomoxys calcitrans. | the gut epithelium is an essential interface in insects that transmit parasites. we investigated the role that local innate immunity might have on vector competence, taking stomoxys calcitrans as a model. s. calcitrans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause african sleeping sickness and nagana. despite this, s. calcitrans is not a cyclical vector of these trypanosomes. trypanosomes develop exclusive ... | 2002 | 12372834 |
| unravelling the origins of trypanosoma brucei rhodesiense. | 2002 | 12377278 | |
| synthesis and evaluation of analogues of 5'-([(z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine as inhibitors of tumor cell growth, trypanosomal growth, and hiv-1 infectivity. | a well-defined series of 5'-([(z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine analogues was designed and synthesized in order to further ascertain the optimal structural requirements for s-adenosylmethionine decarboxylase inhibition and potentially to augment and perhaps separate their antiproliferative and antitrypanosomal activities. most structural modifications had a deleterious affect on both the antitrypanosomal and antineoplastic activity of 5'-([(z)-4-amino-2-butenyl]methylamino)-5' ... | 2002 | 12408722 |
| evaluation of selected sudanese medicinal plants for their in vitro activity against hemoflagellates, selected bacteria, hiv-1-rt and tyrosine kinase inhibitory, and for cytotoxicity. | ethnobotanical investigations led to the selection of 19 plant species, used traditionally in sudan against malaria and other similar tropical diseases, for further studies. pamianthe peruviana (amaryllidaceae) exhibited significant activity against a chloroquine-resistant plasmodium falciparum strain (k1) and a chloroquine-sensitive strain (nf54) with ic(50) values of 0.6 and 1.1 microg/ml, respectively. additionally, p. peruviana showed considerable activities against trypanosoma brucei rhodes ... | 2002 | 12426089 |
| aiming to eliminate tsetse from africa. | the problem of tsetse-transmitted trypanosomiasis occurs only in sub-saharan africa, where it represents a major constraint to socio-economic development. the east african form of sleeping sickness, caused by trypanosoma brucei rhodensiense, is an acute and fatal disease, whereas the west african form, caused by trypanosoma brucei gambiense, is generally more chronic and debilitating. the african governments have developed a new initiative, known as the pan african tsetse and trypanosomiasis era ... | 2002 | 12473355 |
| will the real trypanosoma brucei rhodesiense please step forward? | the sleeping sickness trypanosomes trypanosoma brucei rhodesiense and t. brucei gambiense are morphologically indistinguishable from each other and from t. brucei brucei, which does not infect humans. the relationships between these three subspecies have been controversial. several years ago, the characterization of t. brucei gambiense was reviewed in an attempt to clarify and draw together the results, and to put them in the context of the biology of the organism. the discovery of a gene associ ... | 2002 | 12473364 |
| vernoguinosterol and vernoguinoside, trypanocidal stigmastane derivatives from vernonia guineensis (asteraceae). | two bitter stigmastane derivatives, vernoguinosterol (1) and vernoguinoside (2), have been isolated from the stem bark of vernonia guineensis and their structures eludicated using spectroscopic methods. the new compounds exhibit trypanocidal activity. | 2002 | 11830150 |
| molecular characterization of three gut genes from glossina morsitans morsitans: cathepsin b, zinc-metalloprotease and zinc-carboxypeptidase. | insect gut enzymes are involved in digestion of dietary proteins. additionally, these enzymes have been implicated in the process of pathogen establishment in several insects including the tsetse fly (diptera:glossinidae), which is the vector for african trypanosomes. both the male and female tsetse can transmit trypanosomes and are strict blood feeders during all stages of their development. here, we describe the molecular characterization of three gut genes: cathepsin b (gmcatb), zinc-metallop ... | 2002 | 11841503 |
| [trypanosomiasis--a real risk for tourists visiting national parks in tanzania]. | african sleeping sickness is no longer a rare disease among tourists visiting national parks in tanzania. the disease is caused by a parasite, trypanosoma brucei, which is transmitted by the tsetse fly. two species infect humans: trypanosoma brucci gambiense and trypanosoma brucei rhodesiense; the last form is re-emerging in parts of africa. untreated this disease carries a mortality of nearly 100%. this article describes a case of african sleeping sickness in a tourist visiting tanzania, which ... | 2002 | 11851293 |
| chemotherapy of human african trypanosomiasis. | human african trypanosomiasis or sleeping sickness is resurgent [1,2]. the disease is caused by subspecies of the parasitic haemoflagellate, trypanosoma brucei. infection starts with the bite of an infected tsetse fly (glossina spp.). parasites move from the site of infection to the draining lymphatic vessels and blood stream. the parasites proliferate within the bloodstream and later invade other tissues including the central nervous system. once they have established themselves within the cns, ... | 2002 | 11860365 |
| molecular variation of trypanosoma brucei subspecies as revealed by aflp fingerprinting. | genetic analysis of trypanosoma spp. depends on the detection of variation between strains. we have used the amplified fragment length polymorphism (aflp) technique to develop a convenient and reliable method for genetic characterization of trypanosome (sub)species. aflp accesses multiple independent sites within the genome and would allow a better definition of the relatedness of different trypanosome (sub)species. nine isolates (3 from each t. brucei subspecies) were tested with 40 aflp primer ... | 2002 | 12003059 |
| homology modeling and molecular dynamics study of nad-dependent glycerol-3-phosphate dehydrogenase from trypanosoma brucei rhodesiense, a potential target enzyme for anti-sleeping sickness drug development. | sleeping sickness and chagas disease are among the most severe diseases in africa as well as latin america. these two diseases are caused by trypanosoma spp. recently, an enzyme of a glycolytic pathway, nad-dependent glycerol-3-phosphate dehydrogenase, of leishmania mexicana was crystallized and its structure determined by x-ray crystallography. this structure has offered an excellent template for modeling of the homologous enzymes from another trypanosoma species. here, a homology model of the ... | 2002 | 12023213 |
| activity of bisphosphonates against trypanosoma brucei rhodesiense. | we report the results of a comparative molecular field analysis (comfa) investigation of the growth inhibition of the bloodstream form of trypanosoma brucei rhodesiense trypomastigotes by bisphosphonates. a quantitative three-dimensional structure-activity relationship comfa model for a set of 26 bisphosphonates having a range of activity spanning approximately 3 orders of magnitude (minimum ic(50) = 220 nm; maximum ic(50) = 102 microm) yielded an r(2) value of 0.87 with a cross-validated r(2) v ... | 2002 | 12086478 |
| lepadins d-f: antiplasmodial and antitrypanosomal decahydroquinoline derivatives from the tropical marine tunicate didemnum sp. | from a new tunicate species, belonging to the genus didemnum, three alkaloids possessing an unusual and extremely rare decahydroquinoline skeleton and showing significant and selective antiplasmodial and antitrypanosomal activity were obtained as follows: (2r*,3s*,4ar*,5r*,8as*)-decahydro-3-hydroxy-5-(5'-hydroxyoctyl)-2-methylquinoline (lepadin d,1), its quaternary nitrogen derivative (2), (2r*,2"e,3s*,4ar*,5r*,8as*)-decahydro-3-hydroxy-5-(5'-hydroxyoctyl)-2-methyl-3-quinolinyl ester 2"-octenoic ... | 2002 | 12086492 |
| case records of the massachusetts general hospital. weekly clinicopathological exercises. case 20-2002. a 37-year-old man with fever, hepatosplenomegaly, and a cutaneous foot lesion after a trip to africa. | 2002 | 12087144 | |
| sleeping sickness and the brain. | recent progress in understanding the neuropathological mechanisms of sleeping sickness reveals a complex relationship between the trypanosome parasite that causes this disease and the host nervous system. the pathology of late-stage sleeping sickness, in which the central nervous system is involved, is complicated and is associated with disturbances in the circadian rhythm of sleep. the blood-brain barrier, which separates circulating blood from the central nervous system, regulates the flow of ... | 2002 | 12088284 |
| vsg-gpi anchors of african trypanosomes: their role in macrophage activation and induction of infection-associated immunopathology. | african trypanosomes express a glycosylphosphatidyl inositol (gpi)-anchored variant-specific surface glycoprotein (vsg) as a protective coat. during infection, large amounts of vsg molecules are released into the circulation. their interaction with various cells of the immune system underlies the severe infection-associated pathology. recent results have shown that anti-gpi vaccination can prevent the occurrence of this pathology. | 2002 | 12106794 |
| treatment of human african trypanosomiasis--present situation and needs for research and development. | human african trypanosomiasis re-emerged in the 1980s. however, little progress has been made in the treatment of this disease over the past decades. the first-line treatment for second-stage cases is melarsoprol, a toxic drug in use since 1949. high therapeutic failure rates have been reported recently in several foci. the alternative, eflornithine, is better tolerated but difficult to administer. a third drug, nifurtimox, is a cheap, orally administered drug not yet fully validated for use in ... | 2002 | 12127356 |
| alkaloids from narcissus angustifolius subsp. transcarpathicus (amaryllidaceae). | seven alkaloids have been isolated from fresh bulbs of narcissus angustifolius subsp. transcarpathicus (amaryllidaceae). nangustine, reported here for the first time, is the first 5,11-methanomorphanthridine alkaloid with a c-3/c-4 substitution. the structure and stereochemistry of this new alkaloid, as well as those previously known, have been determined by physical and spectroscopic methods. spectroscopic data of pancracine have been completed. the in vitro assay activity against the parasitic ... | 2002 | 12150811 |
| ancistrocongolines a-d, new naphthylisoquinoline alkaloids from ancistrocladus congolensis. | four new naphthylisoquinoline alkaloids, ancistrocongolines a-d (4-7) were isolated from ancistrocladus congolensis, along with the known compound korupensamine a (8). structural elucidation was achieved by chemical, spectroscopic, and chiroptical methods. their biological activities against the pathogens of malaria, leishmaniasis, chagas disease, and african sleeping sickness were evaluated. | 2002 | 12193010 |
| anti-trypanosomal activity of helenalin and some structurally related sesquiterpene lactones. | the anti-trypanosomal activity of six sesquiterpene lactones (helenalin, mexicanin i, 11alpha,13-dihydrohelenalin acetate, chamissonolide, ivalin and isoalantolactone) against the african trypanosoma brucei rhodesiense and american t. cruzi was investigated. all tested compounds were found active towards both parasites, the former being generally more sensitive. helenalin was the most active compound in the series with ic50 values of 0.051 and 0.695 microm against t. brucei rhodesiense and t. cr ... | 2002 | 12221603 |
| genetic relatedness among trypanosoma evansi stocks by random amplification of polymorphic dna and evaluation of a synapomorphic dna fragment for species-specific diagnosis. | in this study we employed randomly amplified polymorphic dna patterns to assess the genetic relatedness among 14 brazilian trypanosoma evansi stocks from domestic and wild hosts, which are known to differ in biological characteristics. these akinetoplastic stocks were compared with one another, to three old world (ethiopia, china and philippines) dyskinetoplastic stocks of t. evansi, and also with trypanosoma equiperdum, trypanosoma brucei brucei, trypanosoma brucei gambiense and trypanosoma bru ... | 2002 | 11796122 |
| glutathione derivatives active against trypanosoma brucei rhodesiense and t. brucei brucei in vitro. | diesters based on n-benzyloxycarbonyl-s-(2,4-dinitrophenyl) gsh (cbzgsdnp) containing linear alcohols 3 to 9, branched alcohols 10 to 20, or heteroatom linear alcohols 21 to 25, were investigated as in vitro inhibitors of pathogenic parasites. diesters 3 to 25 were better inhibitors of trypanosoma brucei rhodesiense than of t. brucei brucei and had low cytotoxicities. the most active compound had a 50% effective dose (ed(50)) of 0.2 microm. a quantitative structure activity regression equation r ... | 2002 | 11796354 |
| [the epidemiology of human african trypanosomiasis: a complex multifactorial history]. | sleeping sickness has long been known from descriptions by arab merchants and slave traders. however it was not until 1901 that forbes discovered the offending agent and 1903 that bruce described the role of the tsetse fly. the basic epidemiological transmission cycle was described less than 10 years later. although the main outline of the original model can still be considered as sound, subsequent research has greatly expanded our knowledge. molecular biology has identified different parasites ... | 2001 | 11803821 |
| [diagnosis of human african trypanosomiasis in 2001]. | human african trypanosomiasis is characterized by a non-specific clinical presentation with no consistent, pathognomonic manifestations. however definite diagnosis is necessary to avoid unnecessary therapeutic risks with toxic drugs. further complicating this situation is the frequent need to achieve field diagnosis in remote locations with limited facilities. serological tests such as catt (card agglutination trypanosomiasis test) are useful for initial population screening to identify suspects ... | 2001 | 11803824 |
| stage determination and follow-up in sleeping sickness. | in order to select a correct treatment after primary diagnosis of trypanosomiasis infection, accurate assessment of the disease stage, haemo-lymphatic or meningo-encephalitic, is essential. this is achieved by lumbar puncture and subsequent examination of the cerebrospinal fluid. these examinations have to be repeated during 2 years after treatment, and only after the cerebrospinal fluid has normalized one can decide on complete cure. the currently used cerebrospinal fluid parameters, i.e. white ... | 2001 | 11803826 |
| [technical reasons for the re-emergence of sleeping sickness]. | in the 1920s the epidemic outbreak of human african trypanosomiasis was so deadly that government authorities decided to take large-scale action. it was by giving jamot absolute administrative and financial autonomy to apply his ideas that the disease was successfully controlled. after jamot determined efforts against the disease continued so that, by the dawn of decolonization, many considered the problem of sleeping sickness as resolved. control programs progressively slowed and virtually ceas ... | 2001 | 11803836 |
| [distribution and spread of human african trypanosomiasis: value of genetic identification of the trypanosomes]. | numerous factors extrinsic to trypanosome populations have been implicated in the distribution and spread of human african trypanosomiasis (hat), but quantification of these factors has proven difficult. an easier method of monitoring hat consists of tracking parasites by genetic identification of trypanosomes in hosts and vectors. this method requires distinction between trypanosoma brucei rhodesiense and trypanosoma brucei gambiense followed by determination of the genotype of each subspecies ... | 2001 | 11803837 |
| anisomorphic cell division by african trypanosomes. | in the bloodstream of a mammalian host, african trypanosomes are pleomorphic; the shorter, non-proliferative, stumpy forms arise from longer, proliferative, slender forms with differentiation occurring via a range of morphological intermediates. in order to investigate how the onset of morphological change is co-ordinated with exit from the cell cycle we first characterized slender form cell division. outgrowth of the new flagellum was found to occur at a linear rate, so by using outgrowth of th ... | 2001 | 11822664 |
| cytochrome oxidase subunit vi of trypanosoma brucei is imported without a cleaved presequence and is developmentally regulated at both rna and protein levels. | mitochondrial respiration in the african trypanosome undergoes dramatic developmental stage regulation. this requires co-ordinated control of components encoded by both the nuclear genome and the kinetoplast, the unusual mitochondrial genome of these parasites. as a model for understanding the co-ordination of these genomes, we have examined the regulation and mitochondrial import of a nuclear-encoded component of the cytochrome oxidase complex, cytochrome oxidase subunit vi (coxvi). by generati ... | 2001 | 11136449 |
| sleeping sickness: a tale of two diseases. | sleeping sickness presents clinically as two distinct diseases, reflecting the fact that two very different trypanosomes are responsible. the african rift separating east and west africa defines the distribution of the two diseases. in this review, susan welburn, eric fèvre, paul coleman, martin odiit and ian maudlin discuss the biology and distribution of these two diseases in relation to the evolution of hominids in africa. | 2001 | 11137736 |
| new drugs for the treatment of human african trypanosomiasis: research and development. | chemotherapy of human african trypanosomiasis is problematic because of the high frequency of severe adverse events, the long duration and high cost of treatment, and an increasing number of treatment-refractory cases. new cost-efficient, easy-to-use drugs are urgently needed. whereas basic research on potential drug targets is anchored in academia, the complex, highly regulated and very expensive process of preclinical and clinical drug development is almost exclusively in the hands of pharmace ... | 2001 | 11137740 |
| in situ kinetic characterization of methylthioadenosine transport by the adenosine transporter (p2) of the african trypanosoma brucei brucei and trypanosoma brucei rhodesiense. | african trypanosomes are parasitic flagellates that live in the connective tissues of the host. trypanosomes must obtain from their host adenine/adenosine and other nucleosides that can be salvaged through enzymatic cleavage. methylthioadenosine (mta) is a byproduct of polyamine metabolism, formed from the donation of an aminopropyl moiety by decarboxylated s-adenosylmethionine (dcadomet) to form spermidine. mta is then cleaved phosphorolytically by mta phosphorylase to methylthioribose-1-phosph ... | 2001 | 11226379 |
| recombining trypanosome genetics. | 2001 | 11228006 | |
| bisphosphonates inhibit the growth of trypanosoma brucei, trypanosoma cruzi, leishmania donovani, toxoplasma gondii, and plasmodium falciparum: a potential route to chemotherapy. | we have investigated the effects in vitro of a series of bisphosphonates on the proliferation of trypanosoma cruzi, trypanosoma brucei rhodesiense, leishmania donovani, toxoplasma gondii, and plasmodium falciparum. the results show that nitrogen-containing bisphosphonates of the type used in bone resorption therapy have significant activity against parasites, with the aromatic species having in some cases nanomolar or low-micromolar ic(50) activity values against parasite replication (e.g. o-ris ... | 2001 | 11300872 |
| the story of cgp 40 215: studies on its efficacy and pharmacokinetics in african green monkey infected with trypanosoma brucei rhodesiense. | cgp 40 215 is an inhibitor of s-adenosylmethionine decarboxylase, a key enzyme in trypanosomal polyamine biosynthesis. it is highly active against trypanosoma brucei rhodesiense and t. b. gambiense in vitro and in the corresponding rodent models, and therefore was a promising candidate for further development as a new drug against human african trypanosomiasis. we conducted initial pharmacokinetic and efficacy studies in african green monkeys: based on two dose-finding studies, an infection-trea ... | 2001 | 11348531 |
| molecular characterization of field isolates of human pathogenic trypanosomes. | the accurate identification of each of the three subspecies of trypanosoma brucei remains a challenging problem in the epidemiology of sleeping sickness. advances in molecular characterization have revealed a much greater degree of heterogeneity within the species than previously supposed. only group 1 t. b. gambiense stands out as a separate entity, defined by several molecular markers. t. b. rhodesiense is generally too similar to sympatric t. b. brucei strains to be distinguished from them by ... | 2001 | 11348534 |
| identification and characterization of trypanocides by functional expression of an adenosine transporter from trypanosoma brucei in yeast. | the causative agents of sleeping sickness, trypanosoma brucei rhodesiense and t. brucei gambiense, do not synthesize purines de novo but salvage purine bases and nucleosides from their hosts. we used yeast as an expression system for functional characterization of the trypanosomal adenosine transporter tbat1. a selection of purine analogs and flavonoids were tested for their ability to interfere with adenosine transport, with the aims of identifying (a) trypanocidal tbat1 substrates, and (b) inh ... | 2001 | 11357935 |
| analysis of macrophage activation in african trypanosomiasis. | african trypanosomes cause a fatal disease of man and animals that is characterized by extensive functional, histological, and pathological changes in the lymphoid tissues of infected hosts, including an increase in the numbers and activation state of macrophages. macrophage activation during infection is the result of exposure of these cells to parasite components and host-derived ifn-gamma, produced in response to parasite antigens. the balance of these different activation signals may determi ... | 2001 | 11358974 |
| the lysosomal targeting and intracellular metabolism of trypanosome lytic factor by trypanosoma brucei brucei. | trypanosome lytic factor (tlf) provides innate protection for humans against infection by the animal pathogen trypanosoma brucei brucei but not against the agent of human african sleeping sickness, trypanosoma brucei rhodesiense. tlf exists in two forms, tlf-1 and tlf-2. prior studies suggested that tlf-1 causes lysosomal disruption and subsequent cell death in t. b. brucei. here we confirm the lysosomal targeting of tlf-1 by immunolocalization with the trypanosome lysosomal membrane protein p67 ... | 2001 | 11420109 |
| evidence for multiple origins of human infectivity in trypanosoma brucei revealed by minisatellite variant repeat mapping. | in recent years a wide variety of biochemical and molecular typing systems has been employed in the study of parasite diversity aimed at investigating the level of genetic diversity and delineating the relationship between different species and subspecies. however, such methods have failed to differentiate between two of the classically defined subspecies of the protozoan parasite trypanosoma brucei: the human infective, t. b. rhodesiense, which causes african sleeping sickness, and the non-huma ... | 2001 | 11428466 |
| novel inhibitors of trypanosoma cruzi dihydrofolate reductase. | there is an urgent need for the development of new drugs to treat chagas' disease, which is caused by the protozoan parasite trypanosoma cruzi. the enzyme dihydrofolate reductase (dhfr) has been a very successful drug target in a number of diseases and we decided to investigate it as a potential drug target for chagas' disease. a homology model of the enzyme was used to search the cambridge structural database using the program dock 3.5. compounds were then tested against the enzyme and the whol ... | 2001 | 11451529 |
| minor cytotoxic and antibacterial compounds from the rhizomes of amomum aculeatum. | a new cytotoxic 1,7-dioxa-dispiro[5.1.5.2]pentadeca-9,12-dien-11-one derivative, aculeatin d, and a new alkenone, 5-hydroxy-hexacos-1-en-3-one, have been isolated as minor compounds from the rhizomes of amomum aculeatum. their structures have been determined mainly by nmr spectroscopy and mass spectrometry. aculeatin d showed high cytotoxicity against the kb and the l-6 cell line with ic(50) of 0.38 microg/ml and 1 microg/ml, respectively. additionally, it revealed remarkable activity against tw ... | 2001 | 11454360 |
| the epidemiology and control of human african trypanosomiasis. | human african trypanosomiasis is caused by trypanosoma brucei gambiense in west and central africa, and by trypanosoma brucei rhodesiense in east and southern africa. in recent years there has been a dramatic resurgence of gambian trypanosomiasis in central africa, especially in the democratic republic of congo, angola and sudan. the disease is quiescent in most of west africa, as is rhodesian trypanosomiasis the other side of the continent. the epidemiology of gambian trypanosomiasis is reviewe ... | 2001 | 11461032 |
| trypanocidal activity of dicationic compounds related to pentamidine. | eight dicationic compounds related to pentamidine were studied for trypanocidal activity in seven trypanosome isolates. in vitro studies revealed that diamidines are more potent than diimidazolines. for example, 2 (a diamidine) and 4 (a diimidazoline) inhibited the growth of ketri 243 with ic50 values of 2.3 and 900 nm, respectively. introduction of polar groups into the linker decreased the effectiveness of the compounds against drug-resistant trypanosomes. in compounds with a 2-butene linker b ... | 2001 | 11525843 |
| veterinary link to drug resistance in human african trypanosomiasis? | 2001 | 11530144 | |
| the origins of a new trypanosoma brucei rhodesiense sleeping sickness outbreak in eastern uganda. | sleeping sickness, caused by two trypanosome subspecies, trypanosoma brucei gambiense and trypanosoma brucei rhodesiense, is a parasitic disease transmitted by the tsetse fly in sub-saharan africa. we report on a recent outbreak of t b rhodesiense sleeping sickness outside the established south-east ugandan focus, in soroti district where the disease had previously been absent. soroti district has been the subject of large-scale livestock restocking activities and, because domestic cattle are im ... | 2001 | 11530149 |
| cultural and physiological observations on trypanosoma rhodesiense and trypanosoma gambiense. 1949. | 1. a diphasic medium of simple preparation is described for the indefinite cultivation of t. rhodesiense and t. gambiense. 2. the chief advantage of the medium is that it contains rabbit blood and thus obviates the necessity of using human blood. 3. the flagellates develop only to the proventricular stage; hence the cultures are noninfective. 4. the proventricular forms of both t. rhodesiense and t. gambiense consume sugar with the concomitant formation of acid. they are aerobic fermenters. 5. v ... | 2001 | 11534630 |
| the classic paper of tobie, von brand, and mehlman (1950) revisited. | 2001 | 11534631 | |
| chemotherapeutic approaches to protozoa: kinetoplastida--current level of knowledge and outlook. | the possibilities for treating haemoflagellate infections (african trypanosomiasis) are very limited (table 1; mehlhorn and schrevel 1995; croft 1997; hunter 1997; wang 1997; trouiller and olliaro 1998). all the available drugs have severe side-effects in humans and animals. vaccination is not really an option, in view of the wide antigen variability. at present, there are several drug combinations in clinical trials: suramin/eflornithine, suramin/metronidazole, suramin/pentamidine, melarsoprol/ ... | 2001 | 11570565 |
| nitric oxide and cytokine synthesis in human african trypanosomiasis. | plasma and cerebrospinal fluid (csf) concentrations of nitrate and the cytokines interferon (ifn)-gamma, tumor necrosis factor (tnf)-alpha, interleukin (il)-10, and il-4 were measured in 91 african trypanosomiasis patients before and after treatment. nitrate levels overall were not significantly elevated over those for control persons, but a marginal increase in plasma nitrate was detected in patients reporting illness of <40 days' duration. plasma ifn-gamma and total tnf-alpha concentrations in ... | 2001 | 11574928 |
| activity of human trypanosome lytic factor in mice. | the inability of the cattle pathogen trypanosoma brucei brucei to infect humans is due to an innate factor in human serum termed trypanosome lytic factor (tlf). human haptoglobin-related protein is the proposed toxin in tlf and can exist either as a component of a minor subclass of high-density lipoprotein (tlf-1) or as a lipid free, high molecular weight protein complex (tlf-2). the trypanolytic activity of both tlf-1 and tlf-2 has been studied in vitro but their relative contributions to prote ... | 2001 | 11606222 |
| the phenomenon of treatment failures in human african trypanosomiasis. | treatment of human african trypanosomiasis (hat or sleeping sickness) relies on a few drugs which are old, toxic and expensive. the most important drug for the treatment of second stage infection is melarsoprol. during the last 50 years treatment failures with melarsoprol were not a major problem in trypanosoma brucei gambiense patients. commonly a relapse rate of 5-8% was reported, but in recent years it has increased dramatically in some important foci of t. b. gambiense sleeping sickness. tre ... | 2001 | 11703845 |
| active site mapping, biochemical properties and subcellular localization of rhodesain, the major cysteine protease of trypanosoma brucei rhodesiense. | cysteine protease activity of african trypanosome parasites is a target for new chemotherapy using synthetic protease inhibitors. to support this effort and further characterize the enzyme, we expressed and purified rhodesain, the target protease of trypanosoma brucei rhodesiense (mvat4 strain), in reagent quantities from pichia pastoris. rhodesain was secreted as an active, mature protease. site-directed mutagenesis of a cryptic glycosylation motif not previously identified allowed production o ... | 2001 | 11704274 |
| increased trypanolytic activity in sera of sleeping sickness patients after chemotherapy. | we tested sera from patients previously treated for human african trypanosomiasis, from patients infected with trypanosomes, and from individuals never diagnosed with african trypanosomiasis living in the trypanosoma brucei gambiense sleeping sickness focus of mbini in equatorial guinea for their trypanolytic activity against bloodstream forms of t. b. rhodesiense expressing a metacyclic and bloodstream variant surface glycoprotein (vsg). nearly 80% of the sera from treated patients showed high ... | 2001 | 11737844 |
| in vitro antiprotozoal activity of extract and compounds from the stem bark of combretum molle. | the antiprotozoal activity of the ethiopian medicinal plant combretum molle (r. br. ex g. don.) engl & diels (combretaceae) was evaluated by in vitro testing against plasmodium falciparum, trypanosoma brucei rhodesiense, trypanosoma cruzi and leishmania donovani. the acetone fraction of the stem bark of this plant prepared by soxhlet extraction was inactive against the intracellular amastigotes of l. donovani and t. cruzi in murine peritoneal macrophages but showed significant activity against e ... | 2001 | 11746844 |
| identification of human-infective trypanosomes in animal reservoir of sleeping sickness in uganda by means of serum-resistance-associated (sra) gene. | the expansion of sleeping sickness caused by trypanosoma brucei rhodesiense beyond its traditional focus in southeast uganda has been linked with large-scale livestock restocking. to assess the risk presented to the human population by domestic livestock, human-infective t b rhodesiense must be distinguished from non-human-infective t brucei brucei, since both parasites can be present in cattle. we investigated the use of a simple genetic marker to characterise parasites collected from cattle in ... | 2001 | 11755607 |
| kinetics of methionine transport and metabolism by trypanosoma brucei brucei and trypanosoma brucei rhodesiense. | methionine is an essential amino acid for both prokaryotic and eukaryotic organisms; however, little is known concerning its utilization in african trypanosomes, protozoa of the trypanosoma brucei group. this study explored the michaelis-menten kinetic constants for transport and pool formation as well as metabolic utilization of methionine by two divergent strains of african trypanosomes, trypanosoma brucei brucei (a veterinary pathogen), highly sensitive to trypanocidal agents, and trypanosoma ... | 2000 | 10775440 |
| a new bioactive sesterterpene and antiplasmodial alkaloids from the marine sponge hyrtios cf. erecta. | from the ch(2)cl(2) extract of the sponge hyrtios cf. erecta, collected from fiji, two new sesterterpenes, 1 and 2, and the known compounds isodehydroluffariellolide (3), homofascaplysin a (4), and fascaplysin (5) were isolated. the structures of 1-5 were established employing 1d and 2d nmr spectroscopy and mass spectrometry. all nmr resonances of fascaplysin (5) have been unambiguously assigned. evaluation of the biological activity of the extracts and pure compounds toward plasmodium falciparu ... | 2000 | 10869210 |
| fulminant disease simulating bacterial sepsis with disseminated intravascular coagulation after a trip to east africa. | 2000 | 10923746 | |
| african sleeping sickness returns to uk after four years. | 2000 | 11073504 | |
| minisatellite marker analysis of trypanosoma brucei: reconciliation of clonal, panmictic, and epidemic population genetic structures. | the african trypanosome, trypanosoma brucei, has been shown to undergo genetic exchange in the laboratory, but controversy exists as to the role of genetic exchange in natural populations. much of the analysis to date has been derived from isoenzyme or randomly amplified polymorphic dna data with parasite material from a range of hosts and geographical locations. these markers fail to distinguish between the human infective (t. b. rhodesiense) and nonhuman infective (t. b. brucei) "subspecies" s ... | 2000 | 11078512 |
| [value of molecular biology in the identification of trypanosomes responsible for african trypanosomiasis or sleeping sickness]. | 2000 | 11100432 | |
| [melarsoprol]. | 1999 | 10816741 | |
| programmed cell death in procyclic form trypanosoma brucei rhodesiense --identification of differentially expressed genes during con a induced death. | trypanosoma brucei rhodesiense can be induced to undergo apoptosis after stimulation with con a. as cell death in these parasites is associated with de novo gene expression we have applied a differential display technique, randomly amplified differential expressed sequence-polymerase chain reaction (rades-pcr) to the study of gene expression during con a induced cell death in these organisms. twenty-two differentially displayed products have been cloned and sequenced. these represent the first e ... | 1999 | 10224534 |
| the anatomy and transcription of a monocistronic expression site for a metacyclic variant surface glycoprotein gene in trypanosoma brucei. | african trypanosomes evade the immune response of their mammalian hosts by switching the expression of their variant surface glycoprotein genes (vsg). the bloodstream trypanosome clone mvat4 of trypanosoma brucei rhodesiense expresses a metacyclic vsg as a monocistronic rna from a promoter located 2 kilobases (kb) upstream of its start codon. determination of 23 kb of sequence at the metacyclic variant antigen type 4 (mvat) vsg expression site (es) revealed an es-associated gene (esag) 1 precede ... | 1999 | 10358033 |
| inhibition of succinyl coa synthetase histidine-phosphorylation in trypanosoma brucei by an inhibitor of bacterial two-component systems. | recent drug screenings for new antibacterial drugs directed against histidine phospho-relay signalling pathways in bacteria have resulted in compounds which potently inhibit the histidine kinase activity of bacterial two-component systems. the present study demonstrates that one of these compounds, ly266500, is also a potent inhibitor of histidine phosphorylation in the unicellular eukaryotic parasite trypanosoma brucei, both in vitro and in whole cells. in vitro, it inhibits histidine phosphory ... | 1999 | 10376993 |
| metabolic effects of a methylthioadenosine phosphorylase substrate analog on african trypanosomes. | the effects of 5'-deoxy-5'-(hydroxyethylthio)adenosine (heta), a trypanocidal analog of 5'-deoxy-5'-(methylthio)adenosine (mta), on polyamine synthesis and s-adenosylmethionine (adomet) metabolism were examined in bloodstream forms of trypanosoma brucei brucei. heta was cleaved by trypanosome mta phosphorylase at the same rate as the natural substrate, mta, in a phosphate-dependent reaction. fluorine substitution at the 2-position of the purine ring increased activity by approximately 50%, where ... | 1999 | 9920289 |
| ifn-gamma-dependent nitric oxide production is not linked to resistance in experimental african trypanosomiasis. | resistance to african trypanosomes is dependent on b cell and th1 cell responses to the variant surface glycoprotein (vsg). while b cell responses to vsg control levels of parasitemia, the cytokine responses of th1 cells to vsg appear to be linked to the control of parasites in extravascular tissues. we have recently shown that ifn-gamma knockout (ifn-gamma ko) mice are highly susceptible to infection and have reduced levels of macrophage activation compared to the wild-type c57bl/6 (wt) parent ... | 1999 | 10066343 |
| kinetics of s-adenosylmethionine cellular transport and protein methylation in trypanosoma brucei brucei and trypanosoma brucei rhodesiense. | african trypanosomes of the trypanosoma brucei group are agents of disease in man and animals. they present unique biochemical characteristics such as the need for preformed purines and have extensive salvage mechanisms for nucleoside recovery. in this regard we have shown that trypanosomes have a dedicated transporter for s-adenosylmethionine (adomet), a key metabolite in transmethylation reactions and polyamine synthesis. in this study we compared the apparent kinetics of adomet transport, cyt ... | 1999 | 10087160 |
| trypanosomosis agglutination card test for trypanosoma brucei rhodesiense sleeping sickness. | to develop a simple field test for diagnosis of trypanosoma brucei rhodesiense in man. | 1999 | 10442147 |
| plasma nitrate and interferon-gamma in trypanosoma brucei rhodesiense infections: evidence that nitric oxide production is induced during both early blood-stage and late meningoencephalitic-stage infections. | 1999 | 10450441 | |
| tsetse-trypanosome interactions: rites of passage. | trypanosomes that cause sleeping sickness (trypanosoma brucei rhodesiense and t. b. gambiense) are entirely dependent on tsetse for their transmission between hosts, but the flies are not easily infected. this situation has not arisen by chance - the tsetse has evolved an efficient defence system against trypanosome invasion. in this review, susan welburn and ian maudlin chart the progress of trypanosomes through the fly and identify some of the hazards faced by both parasite and fly that affect ... | 1999 | 10481151 |
| activity of extracts and naphthoquinones from kigelia pinnata against trypanosoma brucei brucei and trypanosoma brucei rhodesiense. | dichloromethane extracts of the root bark and stem bark of kigelia pinnata collected from zimbabwe exhibited antitrypanosomal activity against trypanosoma brucei brucei in vitro. activity-guided fractionation led to the isolation of four naphthoquinones from both the root and stem bark of the plant. the compounds were identified as 2-(1-hydroxyethyl)-naphtho[2,3-b]furan-4,9-quinone (1), isopinnatal (2), kigelinol (3), and isokigelinol (4). subsequently, the compounds were assessed for antitrypan ... | 1999 | 10483374 |
| rhodesian trypanosomiasis in a splenectomized patient. | we report the first apparent case of a splenectomized individual who developed severe trypanosomiasis with central nervous system involvement. the patient was a 41-year-old man who participated in an east african safari. upon his return to the united states, the patient presented with an infection with trypanosoma brucei rhodesiense that was treated successfully with suramin and melarsoprol. the onset of symptoms, laboratory studies, and disease progression did not differ from previously reporte ... | 1999 | 10497985 |
| a revised arithmetic model of long slender to short stumpy transformation in the african trypanosomes. | an arithmetic model that closely approximates an african trypanosome infection in immunosuppressed mice is presented. the final model was based on an examination of the following parameters: the rate of long slender to short stumpy transition, the maximum percentage of long slender to short stumpy stages that can be induced, the survival time or half life of the short stumpy stage in vivo, and the rate (%) of long slender to short stumpy stage transition following the peak in transformation. the ... | 1999 | 10577719 |
| molecular characterisation of trypanosoma brucei alkyl dihydroxyacetone-phosphate synthase. | alkyl dihydroxyacetone-phosphate synthase is the second enzyme of the ether-lipid biosynthetic pathway which is responsible for the introduction of the ether linkage between a fatty alcohol and a glycerol present in a subclass of phospholipids, the plasmalogens and possibly in glycolipid membrane anchors. in this study the gene coding for alkyl dihydroxyacetone-phosphate synthase was isolated from trypanosoma brucei. southern blot analysis of total genomic dna suggested the presence of a single ... | 1999 | 10589981 |
| expression and localization of serum resistance associated protein in trypanosoma brucei rhodesiense. | the trypanosome lytic factor (tlf) is a primate specific innate defense mechanism that restricts the host range of african trypanosomes. trypanosoma brucei rhodesiense, the causative agent of the acute form of human sleeping sickness, is resistant to the cytolytic action of tlf. by differential display pcr we have identified a gene in t. b. rhodesiense that is preferentially expressed in cell lines resistant to tlf. the protein sequence predicted from the gene shows homology to the trypanosome v ... | 1999 | 10593181 |
| evidence for the occurrence of trypanosoma brucei rhodesiense sleeping sickness outside the traditional focus in south-eastern uganda. | the occurrence of trypanosoma brucei rhodesiense west of the river nile, in masindi district in the mid-western part of uganda, is confirmed. masindi borders the traditional belt of t. b. gambiense infection in the north-west, gulu in the north and the democratic republic of congo in the west. of the 702 persons tested for sleeping sickness in masindi, 113 (16%) were positive by the card agglutination test for trypanosomiasis (catt). trypanosomes were observed in samples of cerebrospinal fluid ( ... | 1999 | 10715675 |
| prohibitin and rack homologues are up-regulated in trypanosomes induced to undergo apoptosis and in naturally occurring terminally differentiated forms. | two genes have been identified as up-regulated late during cona-induced apoptosis in procyclic form trypanosoma brucei rhodesiense. the first represents a homologue of prohibitin, a proto-oncogene originally described in mammals and subsequently in yeast, which is involved in cell-cycle control and senescence. the trypanosoma prohibitin homologue appears to contain within it a putative death domain. the second gene, homologous to a family of regulatory proteins which are receptors for activated ... | 1998 | 10200516 |
| in vitro and in vivo activities of trybizine hydrochloride against various pathogenic trypanosome species. | trybizine hydrochloride [o,o'-bis(4,6-diamino-1,2-dihydro-2, 2-tetramethylene-s-triazine-1-yl)-1,6-hexanediol dihydrochloride] was active in vitro against the sleeping sickness-causing agents trypanosoma brucei subsp. rhodesiense and t. brucei subsp. gambiense; against a multidrug-resistant organism, t. brucei subsp. brucei; and against animal-pathogenic organisms trypanosoma evansi, trypanosoma equiperdum, and trypanosoma congolense; but not against the intracellular parasites trypanosoma cruzi ... | 1998 | 9797216 |
| human african trypanosomiasis: an emerging public health crisis. | there is a dramatic resurgence of human african trypanosomiasis (hat) in sub-saharan africa. t.b. gambiense is spreading epidemically in large areas of central africa, especially the southern sudan, congo-zaire, angola, uganda and the central african republic. devastating epidemics of t.b. rhodesiense have occurred in south-eastern uganda. the causes of the re-emergence of sleeping sickness as a public health problem include widespread civil disturbance and war, declining economies, reduced heal ... | 1998 | 9830201 |
| treatment of late stage rhodesiense trypanosomiasis using suramin and eflornithine: report of six cases. | 1998 | 9850406 | |
| generation of expressed sequence tags as physical landmarks in the genome of trypanosoma brucei. | previous molecular genetic studies on the african trypanosome have focused on only a few genes and gene products, the majority of which are concerned with surface antigenic variation; consequently, an insignificant number of the genes of this organism have been characterized to date. in order to: (1) identify new genes and analyze their expression profile, (2) generate expressed sequence tags (ests) for derivation of a physical map of the trypanosome genome, and (3) make available the partial se ... | 1998 | 9852954 |
| resistance to the african trypanosomes is ifn-gamma dependent. | the role of variant surface glycoprotein (vsg)-specific th cell responses in determining resistance to the african trypanosomes was examined by comparing th cell responses in relatively resistant and susceptible mice as well as in cytokine gene knockout mice infected with trypanosoma brucei rhodesiense. resistant b10.br and c57bl/6 mice expressed th1 cell cytokine responses to vsg stimulation during infection, while susceptible c3h mice produced weak or no th1 cell cytokine responses. neither re ... | 1998 | 9862708 |
| a vsg expression site-associated gene confers resistance to human serum in trypanosoma rhodesiense. | infectivity of trypanosoma brucei rhodesiense to humans is due to its resistance to a lytic factor present in human serum. in the etat 1 strain this character was associated with antigenic variation, since expression of the etat 1.10 variant surface glycoprotein was required to generate resistant (r) clones. in addition, in this strain transcription of a gene termed sra was detected in r clones only. we show that the etat 1.10 expression site is the one selectively transcribed in r variants. thi ... | 1998 | 9865701 |
| molecular cloning and expression of a purine-specific n-ribohydrolase from trypanosoma brucei brucei. sequence, expression, and molecular analysis. | n-ribohydrolases, including the inosine-adenosine-guanosine-preferring (iag) nucleoside hydrolase, have been proposed to be involved in the nucleoside salvage pathway of protozoan parasites and may constitute rational therapeutic targets for the treatment of these diseases. reported is the complete sequence of the trypanosoma brucei brucei iagnh gene, which encodes iag-nucleoside hydrolase. the 1.4-kilobase iagnh cdna contains an open reading frame of 981 base pairs, corresponding to 327 amino a ... | 1998 | 9442052 |