Wednesday, September 2, 2009

What's new for 'Trypanosomatids' in PubMed

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Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results
Items 1 -9 of 9

1: Pneumonol Alergol Pol. 2009;77(4):417-21.

Tubercular inflammation of cervical lymph nodes with a colliquative tuberculosis focus - a case study.

Owczarek W, Targowski T, Lebkowska K, Paluchowska E.

Cutaneous tuberculosis is a specific form of tuberculosis, characteristic of a differentiated clinical picture and resulting from either endo- or exogenous way of infection, immunological mechanisms and unfavourable conditions for mycobacterium development. The untypical course and symptoms of the disease may cause certain difficulties in obtaining a proper diagnosis and, in consequence, result in delayed onset of appropriate treatment. When diagnosing cutaneous tuberculosis, a broad apparatus of differential diagnostics should be applied, taking into account other diseases such as leishmaniasis, actinomycosis, leprosy or deep mycoses. We report a case of lymph node tuberculosis and of colliquative tuberculosis of the skin, at first erroneously diagnosed as actinomycosis, complicated by multiform erythema. In the reported case, no tuberculous bacilli were identified in bacteriological evaluations of bioptates collected from the skin changes. The final diagnosis of the disease was determined by the presence of specific granulation tissue in the last performed histopathological studies, as well as by hypersensitivity to tuberculin and the presence of mycobacterial DNA in PCR evaluation. According to the authors, in case of clinically suspected cutaneous tuberculosis, repeated (several) histopathological studies of samples from observed changes seem to be fairly justified. The results of histopathological studies should be completed by one of the methods of oligomycobacterial material evaluation, e.g. by identification of mycobacterial genetic material by means of nucleic acid amplification in the PCR method.

PMID: 19722149 [PubMed - in process]

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2: Rev Salud Publica (Bogota). 2009 Jan-Feb;11(1):145-50.

[A report of two cases of disseminated cutaneous leishmaniasis in Santander, Colombia.]

[Article in Spanish]

Rincón MY, Silva SY, Dueñas RE, López-Jaramillo P.

Fundación Cardiovascular de Colombia, Santander, Colombia.

Leishmaniasis is a zoonosis produced by the transmission of the protozoan leishmania caused by the bite of sand-flies from the Lutzomya specie. Several clinical manifestations present themselves, depending on the infecting strain and the host's immune response; the most frequent variety is localised cutaneous leishmaniasis. Atypical forms sometimes develop, such as the diffuse variety, in which the number of ulcers is greater than 10, thereby affecting several body areas requiring special considerations in its diagnosis and management. This article reports two cases of patients from endemic areas of Santander suffering from diffuse cutaneous leishmaniasis produced by the L. panamensis strain. Protocols for the active search of this type of case in endemic areas throughout Colombia should be implemented.

PMID: 19721988 [PubMed - in process]

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3: PLoS Negl Trop Dis. 2009 Sep 1;3(9):e509.

Murine Models for Trypanosoma brucei gambiense Disease Progression-From Silent to Chronic Infections and Early Brain Tropism.

Giroud C, Ottones F, Coustou V, Dacheux D, Biteau N, Miezan B, Van Reet N, Carrington M, Doua F, Baltz T.

UMR 5234, Centre National de Recherche Scientifique, IFR66, Université Bordeaux 2, Bordeaux, France.

BACKGROUND: Human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense remains highly prevalent in west and central Africa and is lethal if left untreated. The major problem is that the disease often evolves toward chronic or asymptomatic forms with low and fluctuating parasitaemia producing apparently aparasitaemic serological suspects who remain untreated because of the toxicity of the chemotherapy. Whether the different types of infections are due to host or parasite factors has been difficult to address, since T. b. gambiense isolated from patients is often not infectious in rodents thus limiting the variety of isolates. METHODOLOGY/PRINCIPAL FINDINGS: T. b. gambiense parasites were outgrown directly from the cerebrospinal fluid of infected patients by in vitro culture and analyzed for their molecular polymorphisms. Experimental murine infections showed that these isolates could be clustered into three groups with different characteristics regarding their in vivo infection properties, immune response and capacity for brain invasion. The first isolate induced a classical chronic infection with a fluctuating blood parasitaemia, an invasion of the central nervous system (CNS), a trypanosome specific-antibody response and death of the animals within 6-8 months. The second group induced a sub-chronic infection resulting in a single wave of parasitaemia after infection, followed by a low parasitaemia with no parasites detected by microscope observations of blood but detected by PCR, and the presence of a specific antibody response. The third isolate induced a silent infection characterised by the absence of microscopically detectable parasites throughout, but infection was detectable by PCR during the whole course of infection. Additionally, specific antibodies were barely detectable when mice were infected with a low number of this group of parasites. In both sub-chronic and chronic infections, most of the mice survived more than one year without major clinical symptoms despite an early dissemination and growth of the parasites in different organs including the CNS, as demonstrated by bioluminescent imaging. CONCLUSIONS/SIGNIFICANCE: Whereas trypanosome characterisation assigned all these isolates to the homogeneous Group I of T. b. gambiense, they clearly induce very different infections in mice thus mimicking the broad clinical diversity observed in HAT due to T. b. gambiense. Therefore, these murine models will be very useful for the understanding of different aspects of the physiopathology of HAT and for the development of new diagnostic tools and drugs.

PMID: 19721701 [PubMed - in process]

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4: Trends Parasitol. 2009 Aug 29. [Epub ahead of print]

Reporter genes facilitating discovery of drugs targeting protozoan parasites.

Dube A, Gupta R, Singh N.

Division of Parasitology, Central Drug Research Institute, Lucknow 226 001, India.

Transfection of protozoan parasites, such as Plasmodium, Leishmania, Trypanosoma and Toxoplasma, with various reporter gene constructs, has revolutionized studies to understand the biology of the host-parasite interactions at the cellular level. It has provided impetus to the development of rapid and reliable drug screens both for established drugs and for new molecules against different parasites and other pathogens. Furthermore, reporter genes have proved to be an excellent and promising tool for studying disease progression. Here, we review the recent advances made by using reporter genes for in vitro and in vivo drug screening, high-throughput screening, whole-animal non-invasive imaging for parasites and for the study of several aspects of host-parasite interactions.

PMID: 19720564 [PubMed - as supplied by publisher]

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5: Vet Parasitol. 2009 Aug 8. [Epub ahead of print]

Canine leishmaniasis in south-east of France: Screening of Leishmania infantum antibodies (western blotting, ELISA) and parasitaemia levels by PCR quantification.

Aoun O, Mary C, Roqueplo C, Marié JL, Terrier O, Levieuge A, Davoust B.

Service Médical, 6(e)/12(e) Régiment de Cuirassiers, Quartier Valmy, 45160 Olivet, France.

Leishmania infantum leishmaniasis is endemic in south-east of France. The main goal of our study was to evaluate the real prevalence of asymptomatic carriage in dogs by means of real time quantitative PCR (qPCR) and serology. We included prospectively 140 military dogs wearing deltamethrine-impregnated collars. Parasitaemia levels were then measured by means of quantitative real time PCR targeting kinetoplast DNA with TaqMan((R)) chemistry. ELISA and western blotting (WB) were used for serological screening. The number of dogs working in three areas was the following: Var (n=48), Bouches-du-Rhône (n=61) and Corsica (n=31). Prevalence of symptomatic dogs was 0.7% (n=1). ELISA and WB were positive in one (0.71%) and 19 (14%) dogs, respectively. Fifty-eight dogs (41.4%) had a positive parasitaemia. Global prevalence (positive WB and/or positive qPCR) was 50% (n=70). Mean parasitaemia was 0.018parasites/mL in the global population and 0.043parasites/mL in positive dogs [min: 0.0002 to max: 2]. The concordance percent for WB and qPCR results was 55% (n=77). Regarding the prevalence of positive parasitaemia, a significant difference was noticed between dogs living in the Var region and those coming from the two other areas. Parasitaemia was rapidly positive within the first semester of stay in an enzootic area. Despite the use of deltamethrine-impregnated collars, the proportion of dogs with low parasitaemia is important. Thus, it may be relevant to evaluate the effect of screening and treating asymptomatic canine reservoirs on human infection by performing further studies comparing both populations.

PMID: 19720466 [PubMed - as supplied by publisher]

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6: Infect Genet Evol. 2009 Aug 28. [Epub ahead of print]

Monitoring the pleomorphism of Trypanosomabruceigambiense isolates in mouse: impact on its transmissibility to Glossina palpalis gambiensis.

Janelle J, Koffi M, Jamonneau V, Patrel D, Cuny G, Ravel S.

CIRAD, UMR17, TA A-17/G, Campus International de Baillarguet, F-34398 Montpellier, France.

Substantial differences have been observed between the cyclical transmission of three Trypanosoma brucei gambiense field isolates in Glossina palpalis gambiensis (Ravel et al., 2006). Differences in the pleomorphism of these isolates in rodent used to provide the infective feed to Glossina, could explain such results, since stumpy forms are preadapted for differentiation to procyclic forms when taken up in a tsetse bloodmeal. To assess this possibility, mice were immunosuppressed and inoculated intraperitoneally with the three isolates (six mice for each trypanosome isolate); then parasitaemia and pleomorphism were determined daily for each mouse. The three T. b. gambiense isolates induced different infection patterns in mouse. The parasitaemia peak was rapidly reached for all the isolates and maintained until mice death for two isolates, while the third isolate rapidly showed a falling phase followed by a second parasitaemia plateau. The proportion of the stumpy forms varied from 15 to 70% over the duration of the experiment and according to the isolate. One isolate, which displayed the highest proportion of stumpy forms and reached the stumpy peak at the onset of the falling phase of parasitaemia, was used to study the relationship between the proportion of stumpy forms and transmissibility to tsetse fly. The results indicated that the transmissibility of trypanosomes was not correlated to the proportion of non-dividing stumpy forms.

PMID: 19720159 [PubMed - as supplied by publisher]

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7: Mol Biochem Parasitol. 2009 Aug 28. [Epub ahead of print]

Leishmania Dihydroxyacetonephosphate Acyltransferase LmDAT is Important for Ether Lipid Biosynthesis but not for the Integrity of Detergent Resistant Membranes.

Zufferey R, Al-Ani GK, Dunlap K.

Department of Biological Sciences, St John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA; Department of Biochemistry, Kansas State University, KS 66506, USA.

Glycerolipid biosynthesis in Leishmania initiates with the acylation of glycerol-3-phosphate by a single glycerol-3-phosphate acyltransferase, LmGAT, or of dihydroxyacetonephosphate by a dihydroxyacetonephosphate acyltransferase, LmDAT. We previously reported that acylation of the precursor dihydroxyacetonephosphate rather than glycerol-3-phosphate is the physiologically relevant pathway for Leishmania parasites. We demonstrated that LmDAT is important for normal growth, survival during the stationary phase, and for virulence. Here, we assessed the role of LmDAT in glycerolipid metabolism and metacyclogenesis. LmDAT was found to be implicated in the biosynthesis of ether glycerolipids, including the ether-lipid derived virulence factor lipophosphoglycan and glycosylphosphatidylinositol-anchored proteins. The null mutant produced longer lipophosphoglycan molecules that were not released in the medium, and augmented levels of glycosylphosphatidylinositol-anchored proteins. In addition, the integrity of detergent resistant membranes was not affected by the absence of the LmDAT gene. Further, our genetic analyses strongly suggest that LmDAT was synthetic lethal with the glycerol-3-phosphate acyltransferase encoding gene LmGAT, implying that Leishmania expresses only two acyltransferases that initiate the biosynthesis of its cellular glycerolipids. Last, despite the fact that LmDAT is important for virulence the null mutant still exhibited the typical characteristics of metacyclics.

PMID: 19720088 [PubMed - as supplied by publisher]

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8: Vector Borne Zoonotic Dis. 2009 Jun;9(3):235-41.Click here to read LinkOut

Leukoreduction by centrifugation does not eliminate Trypanosoma cruzi from infected blood units.

Dzib D, Hernández VP, Ake BC, López RA, Monteón VM.

Centro Estatal de la Transfusión Sanguínea de Campeche, SSA, Campeche, Mexico.

Current strategies to prevent transfusion-associated Chagas disease include the identification of Trypanosoma cruzi-infected blood donors through questionnaires and serologic tests. There are other procedures such as leukoreduction that prevent the transmission of infectious agents associated to white cells. The objective of the present work was to estimate the seroprevalence, evaluate the efficacy of leukoreduction by centrifugation to eliminate T. cruzi in infected blood units, and the correlation of immunoglobulin G (IgG) subclasses of seropositive blood donors with chronic chagasic cardiopathy. Over a period of 14 months, 33 out of 6600 blood donors (0.5%) at Centro Estatal de la Transfusión Sanguínea in Campeche State, México were seropositive for T. cruzi. Twenty seropositive blood units were submitted through leukoreduction by centrifugation, and in the fractions generated (red cell fraction, platelets, and the buffy-coat), we searched for the presence of T. cruzi using specific polymerase chain reaction. We detected parasite DNA in 50% to 60% of the fractions tested, suggesting that leukoreduction by centrifugation does not eliminate the microorganisms in the infected blood unit. We also observed that the level of IgG2 and IgG4 subclasses specific for T. cruzi in seropositive blood donors was lower than in chronic cardiopathic chagasic patients. In conclusion, leukoreduction by centrifugation has a limited role in eliminating T. cruzi in infected blood supply, and the low level of specific IgG2 and IgG4 could be a marker in the indeterminate phase of infection.

PMID: 19485765 [PubMed - indexed for MEDLINE]

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9: Biochim Biophys Acta. 2009 Aug;1794(8):1259-68. Epub 2009 Apr 5.Click here to read LinkOut

Substrate-dependent modulation of enzyme activity by allosteric effector antibodies.

Barlow JN, Conrath K, Steyaert J.

Structural Biology, Free University of Brussels, Brussels, Belgium. jbarlow@vub.ac.be

We investigate the kinetic effects of antibody variable domain fragments derived from heavy chain antibodies (VHH domains) that behave as allosteric effectors of the nucleoside hydrolase from Trypanosoma vivax (TvNH). Strikingly, these antibodies can stimulate or inhibit TvNH steady-state activity, depending on the substrate used. This effect was investigated in greater detail using steady-state and pre-steady-state kinetic experiments. The most potent allosteric effector, VHH 1589, inhibits certain steps on the TvNH catalytic pathway (e.g. N-glycosidic bond cleavage) but increases the rates of others (e.g. substrate and product release). For the natural nucleoside 7-methyl guanosine, where product ribose release is rate determining, the net effect of VHH 1589 binding is to increase k(cat). For the poor substrate pNPR, VHH 1589 causes chemistry (O-glycosidic bond cleavage) to become rate determining and both k(cat)/K(m) and k(cat) to decrease. Thus, the substrate-dependent effects of VHH 1589 binding are caused by differences in the relative rates of chemistry with respect to subsequent steps on the catalytic pathway for these two substrates. We discuss possible mechanisms for these kinetic effects and the implications for allosteric effector drug development.

PMID: 19348968 [PubMed - indexed for MEDLINE]

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