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strain of trypanosoma (trypanozoon) brucei isolated from pigs in bas-zaire. 1977869603
immunoprophylaxis against african trypanosomiasis. 1977339684
an accidental laboratory infection with trypanosomes of a defined stock. ii. studies on the serological response of the patient and the identity of the infecting organism. 19807185920
immune depression and macroglobulinemia in experimental subchronic trypanosomiasis.the effects of subchronic trypanosomiasis upon immune responses were examined in trypanosoma gambiense infection and in subcurative treatment of t. brucei- and t- equiperdum-infected mice. about 60% of the mice infected with t. gambiense developed a subchronic infection similar to human trypanosomiasis, characterized by the absence of circulating trypanosomes. the animals died between 1 and 12 months after infection with elevated serum immunoglobulin m (igm) levels (16 times the normal level). a ...19816788708
macrophages as primary target cells and mediators of immune dysfunction in african trypanosomiasis.african trypanosomiasis is accompanied by profound general immunosuppression. the experiments described here were designed to characterize the contribution of macrophages to the immune pathology of this disease. we used peptone-stimulated, uninfected mice and injected them intraperitoneally with lethally irradiated and 35s-labeled trypanosoma brucei and parasite-specific antisera. peritoneal macrophages were thus induced to take up in vivo a defined number of trypanosomes. after the phagocytosis ...19816114926
incubation of trypanosome-derived mitogenic and immunosuppressive products with peritoneal macrophages allows recovery of biological activities from soluble parasite fractions.this report describes further attempts to define the nature of the parasite product(s) responsible for the extensive changes in lymphoid tissue in mice during infection with trypanosoma brucei. as previously described, potent mitogenic and immunosuppressive effects are induced by a trypanosome-derived crude membrane fraction in vivo. there was no enrichment in these activities when purified parasite surface membranes were used. mitogenic activity can be recovered from soluble trypanosome materia ...19826281187
trypanosomal surface coat variant antigen causes polyclonal lymphocyte activation.variant antigen, the primary component of the surface coat of the salivarian trypanosome, when injected i.v. into mice at dosages encountered during acute infections, produced some of the immunopathogenic phenomena associated with acute african trypanosomiasis. trypanosome-infected and variant antigen-treated mice had splenomegaly caused by proliferation of null cells, b and t lymphocytes, and macrophages. splenic b lymphocytes were nonspecifically activated to produce antibodies to sheep erythr ...19836604754
influence of trypanosoma (t.) brucei brucei infection on delayed-type hypersensitivity to sheep red blood cells in mice. 19836615046
natural agglutinins to african trypanosomes.agglutinins to uncoated culture forms of the african trypanosomes, t. congolense and t.b. brucei were detected in sera from a variety of mammals not exposed to the parasites. the agglutinins in bovine serum were shown to be specific antibodies with opsonic properties selective for the species of trypanosome. these findings suggest a possible role for the glycoprotein coat in preventing access of cross-reacting antibodies to the plasma membrane of african trypanosomes.19836657292
immune mechanisms in c57b1 mice genetically resistant to trypanosoma congolense infection. ii. aspects of the humoral response.some aspects of the humoral response in trypanotolerant c57b1 mice and susceptible a/j mice were investigated to determine the possible basis of trypanotolerance. when the hepatic uptake of 75se-labelled t. congolense by infected mice was measured as an index of antibody production, it was found that only c57b1 mice could remove circulating labelled parasites, this ability persisting for several weeks after infection. estimation of the immunoglobulin concentrations in both strains of mice showed ...19836657296
studies on the influence of non-steroidal anti-inflammatory drugs upon trypanosomiasis in goats and sheep.the non-steroidal anti-inflammatory drug (nsaid) flurbiprofen caused a rise in parasitaemia in goats infected with trypanosoma vivax, trypanosoma congolense and trypanosoma brucei. all trypanosome-infected goats treated with flurbiprofen showed many dividing trypanosomes. this also included the short-stumpy forms of t. brucei. in t. vivax-infected goats flurbiprofen treatment resulted in 100% mortality in the acute and chronic stages of the infection. the increase in parasitaemia of t. brucei in ...19846512919
the use of dna hybridization and numerical taxonomy in determining relationships between trypanosoma brucei stocks and subspecies.the nuclear dnas of 71 trypanosome stocks from different african countries, representative of the three trypanosoma brucei subspecies, and one t. evansi stock, have been analysed by the combined use of restriction endonuclease digestion, gel electrophoresis and molecular hybridization with both trypanosome surface-antigen-specific and undefined genomic dna probes. in contrast with t. brucei brucei and t. brucei rhodesiense stocks, all the t. b. gambiense stocks are characterized by a conserved, ...19863960593
[the sheep: an experimental model for the study of african trypanosomiasis].an experimental model of human african trypanosomiasis is realized in sheep with trypanosoma brucei brucei. clinical and biological evolution is comparable to human disease. this model is useful to test efficient drugs and to get a better knowledge about sleeping sickness physiopathology.19863829214
ejaculate characteristics of sheep infected with trypanosoma brucei and t vivax: changes caused by treatment with diminazene aceturate.the effect of trypanosoma brucei and t vivax on the ejaculate of sheep and the rate of recovery with diminazene aceturate treatment was investigated. animals were made to ejaculate once a week before infection, during infection and after treatment. parameters studied were semen volume, semen colour, sperm motility and concentration, percentage dead spermatozoa and sperm morphology. both infections severely affected the quality of the ejaculate although in t vivax infection there was no appreciab ...19873823622
the sheep (ovis aries) as an experimental model for african trypanosomiasis. ii. biological study.sheep that have been experimentally infected with a strain of trypanosoma brucei brucei reproduce the clinical symptomatology of human african trypanosomiasis. we measured two biochemical parameters which are altered during the infection; total serum and cerebrospinal fluid (csf) proteins, and the time of appearance and levels of igm in both serum and csf. serum protein levels were considerably raised (up to 90 gl-1), although in csf the levels were always less than 1 gl-1. the ratio of serum al ...19883178336
the sheep (ovis aries) as an experimental model for african trypanosomiasis. i. clinical study.sheep were used as an experimental model to study trypanosomiasis. twelve animals were infected with trypanosoma brucei brucei, and the clinical evolution of the disease in the sheep corresponded closely to that described in human patients. the main clinical signs of the experimental infection were hyperthermia, anaemia, loss of weight and behavioural disturbances. death occurred in all cases after a mean time of 75 days. trypanosomes were detected in blood films nine to 15 days after inoculatio ...19883178335
[antiparasitic activity of cis-pt (ii) pentamidine in experimental trypanosomiasis of sheep caused by trypanosoma brucei brucei].the failure of trypanocidal therapeutics have made it a duty to use other classes of molecules which show a comparable trypanocidal efficacy with well-known medicines. in this study, the authors have evaluated the trypanocidal activity of a cis-platinum (ii) salt, dna-intercalating medicine used in antineoplastic therapeutics, associated with pentamidine: cis-pt (ii) pentamidine. after primary screenings on a murine model of t. brucei brucei, cis-pt (ii) pentamidine was evaluated on an experimen ...19883197258
[trial of pentamidine in the treatment of trypanosomiasis of sheep inoculated with trypanosoma brucei brucei].an experimental study was carried out using 5 trypanosoma brucei brucei subcutaneously infected sheep. pentamidine treatment appeared in the csf. two animals were injected daily for 10 days and they died with drug intoxication. two animals received drug every 3 days for 15 days: one of them died, the other was cured after 3 weeks of set-back. this preliminary study should be completed by experimentation made over a more important period of time.19883197257
[treatment of experimental trypanosomiasis of sheep caused by trypanosoma brucei brucei: efficacy of ro 15-0216 (a 2-nitroimidazole derivative)].an experiment was carried out on treatment of trypanosoma brucei brucei experimentally infected sheep with central nervous system involvement with a 2-nitroimidazole derivative: ro 15-0216 (hoffmann la roche & co ltd, basel, switzerland). after a single intramuscularly or intravenously administration (25 or 50 mg/kg) of this compound in healthy sheep, levels of more than 1 microgram/ml corresponding to trypanocidal concentrations are detected in both blood and cerebrospinal fluid. however, becau ...19883197255
[a new series of antiparasitic organic arsenicals: the spiroarsoranes. experimental trypanocidal activity].arsenical compounds are the main therapeutic way, effective in the neurological phase of trypanosomiasis. unfortunately, their important toxicity prevents their easy administration. structural cyclization of arsonic acid derivatives has led to a class of non-toxic compounds: spiroarsoranes. a 47 compound primary screening on an in vivo murine model of trypanosoma brucei brucei resulted in the isolation of a very effective derivative after a single subcutaneous injection of 30 mg.kg-1 body weight ...19883197253
[treatment of experimental trypanosomiasis caused by trypanosoma brucei brucei in sheep: study of the minimum active dose of melarsoprol].trypanosoma brucei brucei experimentally infected sheep with central nervous system involvement were treated with melarsoprol (arsobal, specia, france). the purpose was to determine minimum efficiency concentrations of this drug. eight sheep divided in four groups of two animals were treated intravenously for 3 days with the following respective dosages: 1.8, 0.9, 0.45 and 0.225 mg/kg/d. after a year of observation, efficient dosages were 1.8 and 0.9 mg/kg/d. the experimentation suggests the pos ...19883197250
[complement: a sign of infestation of sheep by trypanosoma brucei brucei in an experimental model: its evolution following treatment].broad variations in complement levels are seen during the course of many infectious diseases, particularly human and animal african trypanosomiasis. in this study, sheep complement is measured by means of its haemolytic activity expressed in 50% haemolytic complement units per ml (hcu50/ml). in healthy sheep, the average value is 23.3 hcu50/ml. complement levels dramatically decrease five days after subcutaneous inoculation of trypanosoma brucei brucei and remain undetectable until death of non ...19883197249
[early auditory evoked potentials in normal sheep and in sheep with trypanosomiasis].in human and animal clinics, the early auditory potential has been used for a long time in the detection of lesions through the internal auditory way in the cerebral trunk. the aim of this work tries to determine if this non invasive test is apt to show up and to follow the evolution of lesions at the level of auditory way in the cerebral trunk of sheep with trypanosomiasis. according to the human technic, the list of the early auditory potential was realized against ten healthy sheep and ten sh ...19883197246
occurrence of human serum-resistant trypanosoma congolense in goats and sheep in nigeria.an assessment of the role of dogs, goats and sheep as reservoir hosts of african trypanosomes infective for humans (sleeping sickness) was carried out in nigeria during a 2-year study period. twelve stocks of trypanosoma (trypanozoon) brucei, 10 stocks of trypanosoma congolense and 11 stocks of trypanosoma vivax were isolated from a total of 699 animals, comprising 286 sheep, 221 goats and 192 dogs. the potential infectivity of the isolates for man was tested in vitro using the blood incubation ...19892741299
[trypanocidal activity and plasma kinetics of cis-pt(ii) pentamidine in the parasitized sheep].the trypanocidal activity of cis-pt(ii) pentamidine had been demonstrated during the first phase of trypanosoma brucei brucei sheep experimental trypanosomiasis. but a subcutaneous treatment with 5 mg.kg-1 (+2 x 12 mg.kg-1) was not effective during the brain phase of trypanosomiasis. the blood pharmacokinetics of this compound had a plasmatic peak between 45 and 60 min, followed by a low decreasing phase along several days. the curve shape allowed an important interval before the following injec ...19902208468
effects of the timing of antigen stimulation on parasitaemia profile and subsequent immunodepression in an experimentally induced trypanosoma brucei infection.the influence of administering sheep red cells (src) as antigens, either after or before a trypanosome challenge, on parasitaemia profile and antibody response was assessed in albino wistar rats. high levels of parasitaemia associated with significantly depressed antibody response and packed cell volume (pcv) values were observed when trypanosome challenge preceded antigen stimulation. in contrast, a clear delay in the onset and development of parasitaemia occurred when antigen priming preceded ...19902103055
trypanosome variant surface glycoprotein transfer to target membranes: a model for the pathogenesis of trypanosomiasis.the variant surface glycoprotein (vsg) of trypanosomes is attached to the cell surface by means of a phosphatidylinositol-containing glycolipid membrane anchor. the studies presented in this paper support the hypothesis that the transfer of vsg from trypanosomes to erythrocytes could lead to one of the pathological features associated with trypanosome infection--i.e., anemia. migration of trypanosome vsg from live trypanosomes to target cells (sheep erythrocytes) could be shown by preincubating ...19902300563
multilocus isozyme identification of trypanosoma brucei stocks isolated in central africa: evidence for an animal reservoir of sleeping sickness in congo.six congolese and 3 zairian trypanosoma brucei stocks were studied by isozyme cellulose acetate electrophoresis. twenty isozyme systems were used, of which only 5 showed variability. these 5 polymorphic systems made it possible to identify 5 different zymodemes. zymodemes isolated from man were recorded both from pig and sheep too, which confirms the results of previous authors. this favors the existence of an animal reservoir of human african trypanosomiasis in the congo, which could play a rol ...19911680279
galactocerebrosides are antigens for immunoglobulins in sera of an experimental model of trypanosomiasis in sheep.in an experimental model of human african trypanosomiasis in sheep inoculated with trypanosoma brucei brucei, we report an immunoglobulin reactivity towards central nervous system (cns) glycolipids. immunocharacterization of the glycolipid antigens was performed on thin-layer chromatography using peroxidase-labelled second antibody. an immunoreactivity against galactocerebroside antigens was observed in inoculated animals up to a dilution of 1:600 and was suppressed after immunoadsorption of ser ...19912027031
a cloned dna probe for cowdria ruminantium hybridizes with eight heartwater strains and detects infected sheep.the dna probe pcs20, which was cloned from the dna of the crystal springs heartwater strain from zimbabwe, cross-reacted with dnas of heartwater strains from all endemic areas, including four heartwater strains from zimbabwe, two strains from south africa, one strain from nigeria, and the gardel strain from the caribbean island of guadeloupe. by nucleic acid hybridization, the pcs20 dna probe detected cowdria ruminantium dna in all dna preparations made from plasma samples from infected sheep be ...19921572987
comparison of the cytolytic effects in vitro on trypanosoma brucei brucei of plasma, high density lipoproteins, and apolipoprotein a-i from hosts both susceptible (cattle and sheep) and resistant (human and baboon) to infection.the african trypanosome, trypanosoma brucei brucei causes a fatal wasting disease in livestock but does not ordinarily infect humans, apparently because this unicellular parasite is lysed by high density lipoproteins (hdl) in human serum. to assess whether there is a specific active constituent in trypanolytic hdl, we have systematically compared the cytotoxic action on t.b.brucei in vitro of native and delipidated hdl, and of individual apolipoproteins, from nonpermissive hosts (human and baboo ...19921527475
transgenic mice expressing human apolipoprotein a-i have sera with modest trypanolytic activity in vitro but remain susceptible to infection by trypanosoma brucei brucei.although trypanosoma brucei brucei fatally infects livestock in much of sub-saharan africa, humans are innately resistant to infection, apparently because high-density lipoproteins (hdl) in human serum lyse this unicellular protozoan parasite. recently, we demonstrated that purified human apolipoprotein (apo) a-i, the major protein (m(r) 28,016) constituent of hdl, had full trypanolytic activity in vitro whereas the apoa-i of cattle and sheep was non-lytic. in the present study, we have sought t ...19921464747
effects of infection with trypanosoma brucei brucei on different trimesters of pregnancy in ewes.the effects of trypanosoma brucei brucei infection during the first, second or third trimesters of pregnancy in 13 ewes were studied. all infected ewes were anaemic with the anaemia being most severe, moderate and least in ewes infected in the second, third and first trimesters, respectively. weight loss occurred in all infected ewes but was most severe in ewes infected in the third trimester. three of the four ewes infected in the first trimester died without aborting while one aborted and late ...19921413452
trypanocidal activity and platinum plasma kinetics of cis-pt pentamidine iodide in trypanosoma brucei sheep model.the trypanocidal properties of cis-pt pentamidine iodide have been studied on the t. b. brucei sheep model. the compound was evaluated on the lymphatic-plasma phase of the disease and appeared to be active on the circulating parasites. cis-pt pentamidine iodide was active at 5 mgl.kg-1 in one single dose both in mouse and sheep trypanosomiasis models. the chemotherapeutic index was about 200 in the mouse. as we observed previously with the chloride derivative, platinum plasma values for cis-pt p ...19938367673
preliminary crystallographic study of 6-phosphogluconate dehydrogenase from trypanosoma brucei.we have obtained well-ordered single crystals of 6-phosphogluconate dehydrogenase, an enzyme of the oxidative branch of the pentose phosphate pathway, from trypanosoma brucei. the crystals are trigonal rhombs with unit cell dimensions a = b = 135.1 a, c = 116.7 a and belong to one of the enantiomorphic pair of space groups p3(1)21/p3(2)21. x-ray diffraction to better than 2.8 a has been recorded using a rotating anode cuk alpha source. elucidation of the three-dimensional structure of the t. bru ...19938377207
african buffalo serum contains novel trypanocidal protein.the high ability of african buffalo, as compared to domestic cattle, to control infections with trypanosoma brucei brucei iltat 1.4 organisms did not correlate with the timing or magnitude of parasite surface coat-specific antibody responses and may have resulted from the constitutive presence in buffalo blood of a novel trypanocidal factor. buffalo plasma and serum contained material that killed bloodstream stage t. b. brucei, t. b. rhodesiense, t. b. gambiense, t. evansi, t. congolense, and t. ...19948167620
serum biochemical changes in west african dwarf sheep experimentally infected with trypanosoma brucei.serum and plasma biochemical values were determined in female west african dwarf sheep experimentally infected with trypanosoma brucei. the results show an increase in the values of serum iron, chloride, bicarbonate, inorganic phosphate, creatinine, urea, total protein, globulin and plasma fibrinogen. the serum albumin, albumin/globulin ratio, potassium, copper and magnesium values are depressed. these findings suggest detective re-utilization of iron in erythropoiesis and probable paratathyroid ...19947863071
[the detection of anti-galactocerebroside autoantibodies in human african trypanosomiasis].the pathogenesis of the central nervous system (cns) damage in human african trypanosomiasis (hat) is unknown. in view of an immunological mechanism, as in another trypanosomiasis, chagas' disease, the causative agent of which is trypanosoma cruzi, we have searched autoantibodies directed against glycosphingolipids of cns. detection and characterization of autoantibodies were performed by elisa and detection after thin-layer chromatography of glycolipids with sera of an experimental model of hat ...19947496196
overexpression in escherichia coli and purification of the 6-phosphogluconate dehydrogenase of trypanosoma brucei.the gene encoding 6-phosphogluconate dehydrogenase (ec 1.1.1.44) from trypanosoma brucei was cloned into the overexpression vector pet3a which utilizes the t7 polymerase gene expression system. up to 40% of total cell protein consisted of the trypanosome enzyme when expression was induced in escherichia coli host strains at 28 degrees c. the enzyme was rapidly degraded at temperatures higher than 30 degrees c. the t. brucei enzyme was purified to near homogeneity (as judged by sds-polyacrylamide ...19948167473
trypanosoma brucei brucei: antitrypanosomal evaluation of stilbamidinium hexachloroiridiate on the murine cns model and iridium serum kinetics in infected sheep.stilbamidinium hexachloroiridiate was found trypanocidal in vitro against trypanosoma brucei brucei ipp at 600 microm after a 1 h incubation period and 30 microm after 24 h. this activity was confirmed in mice with a subcutaneous treatment at 20 mg/kg in a single dose. it was then evaluated on t.b. brucei murine cns model. at the early stage, a subcutaneous treatment at 2 mg/kg/day x 5 cured 50% mice where-as one single dose at 10 mg/kg was completely inactive. higher doses failed to cure the mi ...19957631127
evaluation of three antigen detection tests (monoclonal trapping elisa) for african trypanosomes, with an isolate of trypanosoma vivax from french guyana.preliminary studies in french guyana with sheep experimentally infected with a local isolate of trypanosoma vivax tended to show poor sensitivity and/or specificity of the monoclonal antibodies used in kits for the antigen-detection (ag) elisa for t. vivax, t. brucei, and t. congolense. to reevaluate these kits, 4 calves were infected at ilrad, nairobi, kenya, with the same isolate. blood samples were taken daily for 51 days, and examined directly on blood smears and buffy coat, and using ag-eli ...19968784499
inhibition of growth of trypanosoma brucei parasites in chronic infections.the growth of trypanosoma brucei parasites in chronic infections was investigated by superimposing upon chronic infections, secondary infections in which all parasites expressed the same variable antigen type (vat). the fate of trypanosomes in secondary infections could then be monitored using the vat as a marker to discriminate cells in primary and secondary infections and thus enable growth to be observed separately from its interactions with antigenic variation on the part of the parasite and ...19968825447
6-phosphogluconate dehydrogenase from trypanosoma brucei. kinetic analysis and inhibition by trypanocidal drugs.the kinetics of 6-phosphogluconate dehydrogenase from trypanosoma brucei was examined and compared to those of the same enzyme from lamb's liver. variation of kinetic parameters as a function of ph suggests a chemical mechanism similar to other 6-phosphogluconate dehydrogenases. the comparison extended to a detailed analysis of the effect on enzyme activity by several inhibitors including the trypanocidal drugs suramin, melarsoprol and analogues of these compounds. the t. brucei enzyme differs s ...19968856059
the cross-linking by o-phthalaldehyde of two amino acid residues at the active site of 6-phosphogluconate dehydrogenase.o-phthalaldehyde inactivates homodimeric, nadp+ dependent, 6-phosphogluconate dehydrogenase from sheep liver, upon formation of a single isoindole derivative per enzyme subunit. this indicates that the thiol group of a cysteine residue or the epsilon-amino group of a lysine residue located within 3 a and crosslinked by the reagent is essential for catalysis. fluorescence analyses of the modified enzyme suggest that the isoindole derivative forms at the binding site of the nicotinamide moiety of ...19979315293
trypanocidal effect of ir-(cod)-pentamidine tetraphenylborate on trypanosoma brucei and t. b. gambiense rodent models and serum kinetics in sheep.pentamidine di-(iridium cyclo-octadiene)tetraphenylborate, called ir-(cod)-pentamidine tetraphenylborate, was selected from a primary screening as a promising trypanocidal compound. the compound was evaluated against three isolates: trypanosoma brucei brucei cmp, t.b. brucei gvr 35 and t.b. gambiense feo. on the t.b. brucei gvr 35 murine cns model, no mouse was cured when the treatment was commenced 21 days post-infection whatever the treatment regimen. nevertheless, in vitro the compound killed ...19979018299
detection of trypanosoma brucei, t. congolense and t. vivax infections in cattle, sheep and goats using latex agglutination.a monoclonal antibody-based latex agglutination test for detection of circulating trypanosome antigens in animal serum was evaluated for the ability to detect natural t. brucei, t. congolense and t. vivax infections in cattle, sheep and goats in ghana. the test detected antigens in 180/422 (42.7%) of cattle, 27/131 (20.6%) of sheep and 14/79 (17.7%) of the goats. by comparison, the microplate-based antigen-elisa gave similar results (p > 0.01), detecting trypanosome antigens in 41.7% of the catt ...19979076533
[human african trypanosomiasis, contributions of experimental models].melarsoprol has remained the chosen drug for the late-stage treatment of human african trypanosomiasis (hat) due both to trypanosoma brucei (t.b.) gambiense and t.b. rhodesiense; however, arsenical encephalopathies, which are often fatal, occur in 5-10% of the treated cases. to date, two major problems have not been solved. the first one is the precise diagnosis of early involvement of the central nervous system (cns) which determines the therapeutics to be administered. the second one is linked ...19989642464
a 2.8 a resolution structure of 6-phosphogluconate dehydrogenase from the protozoan parasite trypanosoma brucei: comparison with the sheep enzyme accounts for differences in activity with coenzyme and substrate analogues.the three-dimensional structure of 6-phosphogluconate dehydrogenase (6pgdh) from the parasitic protozoan trypanosoma brucei has been solved at 2.8 a resolution. this pentose phosphate pathway enzyme is nadp-dependent; nadph generated in the reaction protects against oxidative stress. the enzyme crystallises in the space-group p3121 with a dimer in the asymmetric unit and cell dimensions a=b=135.13 a, c=116.74 a, alpha=beta=90 degrees, gamma=120 degrees. the structure has refined to r=18.6% (rfre ...19989737929
6-phosphogluconate dehydrogenase: the mechanism of action investigated by a comparison of the enzyme from different species.the mechanism of action of 6-phosphogluconate dehydrogenase with the alternative substrate 2-deoxy 6-phosphogluconate was investigated using enzymes from sheep liver, human erythrocytes and trypanosoma brucei. the three enzymes oxidize 2-deoxy 6-phosphogluconate, but only the sheep liver enzyme releases the intermediate 2-deoxy,3-keto 6-phosphogluconate. kinetic comparison showed that an increase in the rate of nadp+ reduction at high ph is due to increased release of the intermediate, rather th ...19989920387
6-phosphogluconate dehydrogenase from lactococcus lactis: a role for arginine residues in binding substrate and coenzyme.a gene encoding 6-phosphogluconate dehydrogenase (6-pgdh, ec 1.1.1. 44) was identified from the homofermentative lactic acid bacterium lactococcus lactis, by complementation of escherichia coli mutants. the cloned gene was then expressed to high levels in e. coli and the protein purified for kinetic analysis. the enzyme had a km for 6-phosphogluconate of 15.4+/-1.4 microm and for nadp of 1.9+/-0.2 microm at ph 7.5. sequence comparison of the l. lactis 6-pgdh with the corresponding enzyme derived ...19999931298
chalcone, acyl hydrazide, and related amides kill cultured trypanosoma brucei brucei.protozoan parasites of the genus trypanosoma cause disease in a wide range of mammalian hosts. trypanosoma brucei brucei, transmitted by tsetse fly to cattle, causes a disease (nagana) of great economic importance in parts of africa. t. b. brucei also serves as a model for related trypanosoma species, which cause human sleeping sickness.200011055585
antitrypanosomal properties of cis-platinum-pentamidine bromide, thiocyanate and seleniocyanate on trypanosoma brucei brucei mouse and sheep models.three organometallic complexes derived from pentamidine were evaluated for their trypanocidal effect on in vivo trypanosoma brucei brucei models in comparison to pentamidine isethionate as reference compound. on the t. b.brucei mouse model, the most active compound was cis-platinum-pentamidine bromide. this compound was active when subcutaneously administered at the single dose of 1.5 micromol/kg and its chemotherapeutic index was 200 whereas pentamidine isethionate was active at 6 micromol/kg w ...200111233802
the analysis of the cross-reactions occurring in antibody-elisa for the detection of trypanosomes can improve identification of the parasite species involved.in africa, the main pathogenic trypanosomes of livestock are trypanosoma vivax, t. congolense and t. brucei. the geographical distributions and hosts of these three species are very similar. as they differ markedly in pathogenicity and epidemiology, however, a species-specific serological test for infection would be very useful for epidemiological studies. the antibody-elisa (ab-elisa) that have been developed for detecting the trypanosoma spp. most commonly infecting livestock give satisfactory ...200111299121
selective inhibition of 6-phosphogluconate dehydrogenase from trypanosoma brucei.a number of triphenylmethane derivatives have been screened against 6-phosphogluconate dehydrogenase from trypanosoma brucei and sheep liver. some of these compounds show good inhibition of the enzymes and also selectivity towards the parasite enzyme. modelling was undertaken to dock the compounds into the active sites of both enzymes. using a combination of dock 3.5 and flexidock a correlation was obtained between docking score and both activity for the enzymes and selectivity. visualisation of ...200111394739
sugar derivatives as new 6-phosphogluconate dehydrogenase inhibitors selective for the parasite trypanosoma brucei.sugar derivatives mimicking compounds which take part in the catalysed reaction have been assayed as alternative substrates and/or competitive inhibitors of 6-phosphogluconate dehydrogenase from trypanosoma brucei and sheep liver. phosphonate analogues have been synthesised and the new compound 5-deoxy-5-phosphono-d-arabinonate shows good selectivity towards the parasite enzyme. a number of 4-carbon and 5-carbon aldonates are strong inhibitors of the parasite enzyme with k(i) values below the su ...200312628648
domestic animals as reservoirs for sleeping sickness in three endemic foci in south-eastern uganda.the persistence of sleeping sickness (human african trypanosomiasis) in some areas of south-eastern uganda has necessitated further investigations, focusing mainly on domestic animals as reservoirs of this disease in three agro-ecological zones. the inter-zone differences in the prevalences of trypanosome infection among cattle (p < 0.001) and pigs (p < 0.001) were significant. overall, 5.0% of the cattle, 13.9% of the pigs and 0.4% of the small ruminants investigated were found to be infected w ...200312803870
synthesis and biological evaluation of substrate-based inhibitors of 6-phosphogluconate dehydrogenase as potential drugs against african trypanosomiasis.the synthesis and biological evaluation of three series of 6-phosphogluconate (6pg) analogues is described. (2r)-2-methyl-4,5-dideoxy, (2r)-2-methyl-4-deoxy and 2,4-dideoxy analogues of 6pg were tested as inhibitors of 6-phosphogluconate dehydrogenase (6pgdh) from sheep liver and also trypanosoma brucei where the enzyme is a validated drug target. among the three series of analogues, seven compounds were found to competitively inhibit 6pgdh from t. brucei and sheep liver enzymes at micromolar co ...200312818683
the leucocytic and parasitaemic profiles and immune response of rats treated with retinyl palmitate before infection with trypanosoma brucei.the effects of oral administration of retinyl palmitate (30,000 iu/kg bodyweight) for 3 days to rats before infection with trypanosoma brucei were investigated by examining the leucocytic and parasitaemic profiles, and the antibody response to sheep red blood cells. the pretreatment significantly (p<0.01) improved the leucocytic profile (especially the absolute lymphocyte count) from day 7 post-infection to the time of death. it also significantly delayed the onset of parasitaemia (i.e., lengthe ...200314554122
plasma kinetics and efficacy of oral megazol treatment in trypanosoma brucei brucei-infected sheep.experimentally infected sheep have been previously developed as an animal model of trypanosomosis. we used this model to test the efficacy of megazol on eleven trypanosoma brucei brucei-infected sheep. when parasites were found in blood on day 11 post-infection, megazol was orally administered at a single dose of 40 or 80mg/kg. after a transient aparasitaemic period, all animals except two relapsed starting at day 2 post-treatment, which were considerated as cured on day 150 post-treatment and s ...200415135860
selective inhibition of trypanosoma brucei 6-phosphogluconate dehydrogenase by high-energy intermediate and transition-state analogues.two series of compounds were designed to mimic the transition state and high-energy intermediates (hei) of the enzymatic reaction of 6-phosphogluconate dehydrogenase (6pgdh). sulfoxide analogues (7-11) were designed to mimic the transition state during the oxidation of the substrate to 3-keto-6-phosphogluconate, an enzyme-bound intermediate of the enzyme. hydroxamate and amide derivatives of d-erythronic acid were designed to mimic the 1,2-cis-enediol hei of the 6pgdh reaction. these two series ...200415189039
a comparative study on the susceptibility of male and female albino mice to trypanosoma brucei brucei.trypanosomiasis has remained a major set-back in the development of livestock farming in tropical africa. thus the need for ascertaining the trypanotolerant levels of domestic animal breeds and possible improvement on them cannot be over-emphasised.200515999456
crystal structures of a bacterial 6-phosphogluconate dehydrogenase reveal aspects of specificity, mechanism and mode of inhibition by analogues of high-energy reaction intermediates.crystal structures of recombinant lactococcus lactis 6-phosphogluconate dehydrogenase (llpdh) in complex with substrate, cofactor, product and inhibitors have been determined. llpdh shares significant sequence identity with the enzymes from sheep liver and the protozoan parasite trypanosoma brucei for which structures have been reported. comparisons indicate that the key residues in the active site are highly conserved, as are the interactions with the cofactor and the product ribulose 5-phospha ...200717222187
factors affecting trypanosome maturation in tsetse flies.trypanosoma brucei brucei infections which establish successfully in the tsetse fly midgut may subsequently mature into mammalian infective trypanosomes in the salivary glands. this maturation is not automatic and the control of these events is complex. utilising direct in vivo feeding experiments, we report maturation of t. b. brucei infections in tsetse is regulated by antioxidants as well as environmental stimuli. dissection of the maturation process provides opportunities to develop transmis ...200717318257
trypanosoma evansi: molecular homogeneity as inferred by phenetical analysis of ribosomal internal transcribed spacers dna of an eclectic parasite.the protozoan trypanosoma evansi is described as presenting high morphological and genetic similarities among the isolates despite its biological heterogeneity and wide geographical distribution. pcr amplification of the internal transcribed spacers of the ribosomal gene in combination with the coding region of the 5.8s ribosomal subunit further submitted to restriction enzymes digestion were carried out in dnas extracted from 41 t. evansi strains isolated from horses, dogs, coatis and capybaras ...200818158150
comparative histopathology of the lymph nodes, spleen, liver and kidney in experimental ovine trypanosomosis.the infection of yankassa rams with three important trypanosome species affecting livestock, namely, trypanosoma congolense, t. vivax and t. bruceiproduced both acute and chronic fatal conditions. chronic infections were induced in the three infections by the application of subcurative doses of diaminazene aceturate (berenil). pathological changes in the infected animals included splenomegaly and hepatomegaly which were more pronounced in acute than in chronic t. congolense infection. however, t ...200921344787
domestic animals as potential reservoir hosts of trypanosoma brucei gambiense in sleeping sickness foci in cameroon.an explanation of the endemic nature and/or the resurgence of human african trypanosomiasis (hat) in the historic foci in west and central africa may be the existence of an animal reservoir. in some hat foci, pigs were found infected by trypanosoma brucei gambiense but the implication of the other domestic animals was not quite evaluated. this study aims to determine the prevalence of t. b. gambiense in domestic animal species (goat, sheep, pig and dog) commonly found in the four active hat foci ...201020387740
no gold standard estimation of the sensitivity and specificity of two molecular diagnostic protocols for trypanosoma brucei spp. in western kenya.african animal trypanosomiasis is caused by a range of tsetse transmitted protozoan parasites includingtrypanosoma vivax, trypanosoma congolense and trypansoma brucei. in western kenya and other parts of east africa two subspecies of t. brucei, t.b. brucei and the zoonotict.b. rhodesiense, co-circulate in livestock. a range of polymerase chain reactions (pcr) have been developed as important molecular diagnostic tools for epidemiological investigations of t. brucei s.l. in the animal reservoir a ...201020062795
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