Thursday, October 29, 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 -8 of 8

1. Pharm Unserer Zeit. 2009 Oct 27;38(6):552-558. [Epub ahead of print]

Wirkstoffe zur Behandlung der Afrikanischen Schlafkrankheit. Im letzten Jahrhundert entwickelt.

Schlitzer M.

Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, 35032 Marburg.

Insgesamt ist die Auswahl an Wirkstoffen zur Behandlung der Afrikanischen Schlafkrankheit begrenzt. Die meisten Substanzen wurden bereits in der ersten Hälfte des vorigen Jahrhunderts eingeführt. Unter Anwendung der heute gültigen Regeln, wäre wohl keine davon entwickelt, geschweige denn zugelassen worden. Nebenwirkungen und (im Fall des Melarsoprols) Resistenz sind die grössten Probleme dieser Substanzen. Eine neuere Entwicklung ist die Kombination von Eflornithin mit Nifurtimox, die in ersten klinischen Tests im Spätstadium der Infektion mit T. brucei gambiense anderen Kombinationen überlegen war. Für die Therapie des Spätstadiums der Infektion mit T. brucei rhodesiense bleibt aber weiterhin nur das Melarsoprol mit all seinen Problemen.Nur eine neue Substanz (Parfuramidin), die zumindest theoretisch eine Kreuzresistenz mit Melarsoprol aufweisen könnte, ist in der klinischen Entwicklung. Ihr weiteres Schicksal ist momentan ungewiss. Zahlreiche biologische Targets und entsprechende Hemmstoffe sind beschrieben, es steht allerdings nicht zu erwarten, dass diese Entwicklungen kurzfristig zu neuen Therapien führen werden.

PMID: 19862727 [PubMed - as supplied by publisher]
2. Pharm Unserer Zeit. 2009 Oct 27;38(6):538-544. [Epub ahead of print]

Wirkstoffe zur Behandlung von Leishmaniosen. Antimon und mehr.

Ryczak J, Kunick C.

Institut für Pharmazeutische Chemie Technische Universität Carolo-Wilhelmina zu Braunschweig, Beethovenstrasse 55, 38106 Braunschweig.

Infektionen mit einzelligen Parasiten der Gattung Leishmania verursachen sehr unterschiedliche Krankheitsbilder. Obwohl in den ärmeren Ländern der Subtropen und Tropen mehr als 10 Millionen Menschen an diesen Erkrankungen leiden, wird ihnen in den Industrieländern wenig Aufmerksamkeit entgegengebracht. Die in der Vergangenheit relativ bescheidenen Forschungsaktivitäten zur Suche nach antileishmaniellen Wirkstoffen sind dafür verantwortlich, dass die aktuell verfügbaren Therapieoptionen begrenzt sind.

PMID: 19862714 [PubMed - as supplied by publisher]
3. Int J Biochem Cell Biol. 2009 Oct 24. [Epub ahead of print]

Acidic Residues in the Purine Binding Site Govern the 6-Oxopurine Specificity of the Leishmania donovani Xanthine Phosphoribosyltransferase.

Ullman B, Cyr N, Choi K, Jardim A.

Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, OR 97239.

Leishmania possess distinct xanthine phosphoribosyltransferase and hypoxanthine-guanine phosphoribosyltransferase enzymes that mediate purine salvage, an obligatory nutritional function for these pathogenic parasites. The xanthine phosphoribosyltransferase preferentially uses xanthine as a substrate, while the hypoxanthine-guanine phosphoribosyltransferase phosphoribosylates only hypoxanthine and guanine. These related phosphoribosyltransferases were used as model system to investigate the molecular determinants regulating the 6-oxopurine specificity of these enzymes. Analysis of the purine binding domains showed two conserved acidic amino acids; glutamate residues in the xanthine phosphoribosyltransferase (E198 and E215) and aspartate residues in the hypoxanthine-guanine phosphoribosyltransferase (D168 and D185). Genetic and biochemical analysis established that the single E198D and E215D mutations increased the turnover rates of the xanthine phosphoribosyltransferase without altering purine nucleobase specificity. However, the E215Q and E198,215D mutations converted the Leishmania xanthine phosphoribosyltransferase into a broad-specificity enzyme capable of utilizing guanine, hypoxanthine, and xanthine as substrates. Similarly, the D168,185E double mutation transformed the Leishmania hypoxanthine-guanine phosphoribosyltransferase into a mutant enzyme capable phosphoribosylating only xanthine, albeit with a much lower catalytic efficiency. These studies established that these conserved acidic residues play an important role in governing the nucleobase selectivity of the Leishmania 6-oxopurine phosphoribosyltransferases.

PMID: 19861168 [PubMed - as supplied by publisher]
4. Emerg Infect Dis. 2009 Oct;15(10):1706-7.

Appropriate Screening for Leishmaniasis before Immunosuppressive Treatments.

Cascio A, Iaria C.

University of Messina, Messina, Italy (A. Cascio); and Sapienza University of Rome, Rome, Italy (C. Iaria).

To the Editor: We read with great interest the article by Xynos et al. reporting 2 cases of leishmaniasis in patients treated with biologic drugs (1). Although we agree with most of the article, we are not totally convinced that serologic analysis alone could be used to screen for leishmaniasis before initiation of biologic or immunosuppressive treatments. Evidence indicates that serologic analysis can identify only symptomatic or asymptomatic cases with recent and still active infection (2,3).

PMID: 19861088 [PubMed - in process]
5. Am J Trop Med Hyg. 2009 Oct;81(4):656-9.

Molecular epidemiology of Chagas disease in the wild transmission cycle: the evaluation in the sylvatic vector Mepraia spinolai from an endemic area of Chile.

Coronado X, Rozas M, Botto-Mahan C, Ortíz S, Cattan PE, Solari A.

Programa de Biología Celular y Molecular, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.

The sylvatic transmission cycle of Chagas disease in Chile is composed of wild mammals and insects of the genus Mepraia. We determined infection rates and Trypanosoma cruzi genotypes in Mepraia spinolai. We collected 227 insects from two ecologically contrasting areas to assess T. cruzi infection. Polymerase chain reaction (PCR)-amplified minicircle DNAs were characterized by Southern blot and hybridization tests with genotype-specific probes. Infection in insects from the more fertile area was almost 2-fold higher than in the poorer area. The genotype TCI was the most prevalent and other genotypes such as TCIIb, TCIId, and TCIIe were found at lower rates. The areas differed in their genotype distribution but not in their genotype diversity. We suggest that the difference in abundance and richness of mammals between the areas may be producing the detected infection levels in vectors. Our results are compared with those reported for mammals from the same area.

PMID: 19815882 [PubMed - indexed for MEDLINE]
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Publication Types:

  • Research Support, Non-U.S. Gov't

MeSH Terms:

  • Animals
  • Chagas Disease/epidemiology*
  • Chagas Disease/transmission
  • Chile/epidemiology
  • Endemic Diseases
  • Epidemiology, Molecular*
  • Genotype
  • Insect Vectors
  • Nymph
  • Triatominae/parasitology*
  • Trypanosoma cruzi/genetics
  • Trypanosoma cruzi/isolation & purification*
6. Exp Parasitol. 2009 Dec;123(4):326-33. Epub 2009 Aug 22.

Trypanosoma cruzi calmodulin: cloning, expression and characterization.

Garcia-Marchan Y, Sojo F, Rodriguez E, Zerpa N, Malave C, Galindo-Castro I, Salerno M, Benaim G.

Centro de Biociencias y Medicina Molecular, Instituto de Estudios Avanzados (IDEA), Universidad Central de Venezuela, Caracas 1080, Bolivarian Republic of Venezuela.

We have cloned and expressed calmodulin (CaM) from Trypanosoma cruzi, for the first time, to obtain large amounts of protein. CaM is a very well conserved protein throughout evolution, sharing 100% amino acid sequence identity between different vertebrates and 99% between trypanosomatids. However, there is 89% amino acid sequence identity between T. cruzi and vertebrate CaMs. The results demonstrate significant differences between calmodulin from T. cruzi and mammals. First, a polyclonal antibody developed in an egg-yolk system to the T. cruzi CaM recognizes the autologous CaM but not the CaM from rat. Second, it undergoes a larger increase in the alpha-helix content upon binding with Ca(2+), when compared to CaM from vertebrates. Finally, two classic CaM antagonists, calmidazolium and trifluoperazine, capable of inhibiting the action of CaM in mammals when assayed on the plasma membrane Ca(2+) pump, showed a significant loss of activity when assayed upon stimulation with the T. cruzi CaM.

PMID: 19703447 [PubMed - indexed for MEDLINE]
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Publication Types:

  • Research Support, Non-U.S. Gov't

MeSH Terms:

  • Animals
  • Antibodies, Protozoan/biosynthesis
  • Calcium-Transporting ATPases/blood
  • Calmodulin/biosynthesis*
  • Calmodulin/chemistry
  • Calmodulin/genetics
  • Calmodulin/immunology
  • Chickens
  • Circular Dichroism
  • Cloning, Molecular
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Activation
  • Enzyme-Linked Immunosorbent Assay
  • Erythrocyte Membrane/enzymology
  • Female
  • Gene Expression Regulation
  • Humans
  • Immunoglobulins/biosynthesis
  • Recombinant Proteins/chemistry
  • Recombinant Proteins/genetics
  • Recombinant Proteins/immunology
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Trypanosoma cruzi/chemistry
  • Trypanosoma cruzi/genetics
  • Trypanosoma cruzi/metabolism*

Substances:

  • Antibodies, Protozoan
  • Calmodulin
  • IgY
  • Immunoglobulins
  • Recombinant Proteins
  • Calcium-Transporting ATPases
7. Exp Parasitol. 2009 Dec;123(4):309-12. Epub 2009 Aug 19.

Trypanosoma cruzi: biodistribution of technetium-99m pertechnetate in infected rats.

Barbosa VS, Holanda CM, Câmara AC, Silva RP, Oliveira DP, Moreira JA, Medeiros AC.

Postgraduate Program for Health Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.

With the aim of investigating the biodistribution of technetium-99m pertechnetate ((99m)TcO4-) in rats infected with Y strain of Tripanosoma Cruzi, at the peak of parasitemia, (14th day of infection), we injected Wistar rats with 0.1 ml of (99m)TcO4- (3.7MBq). After 60 min, the percentage of radioactivity per gram was counted in several isolated organs and blood, using a gamma counter (1470 Wizard, PerkinElmer Finland). The uptake of (99m)TcO4- increased significantly in blood and decreased in the colon of infected animals (p<0.05). A significant reduction in serum iron and red blood cells and a significant increase in total proteins, leukocytes and lymphocytes in the infected rats were observed, compared with controls (p<0.05). A reduction in muscle layer thickness of the colon and mononuclear inflammation were observed. These results conclusively demonstrate that T. cruzi infection would be associated with changes in the biodistribution of (99m)TcO4- and in colon morphology, with potential clinical implications.

PMID: 19698711 [PubMed - indexed for MEDLINE]
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MeSH Terms:

  • Animals
  • Chagas Disease/metabolism*
  • Chagas Disease/parasitology
  • Chagas Disease/radionuclide imaging
  • Male
  • Parasitemia/metabolism*
  • Parasitemia/parasitology
  • Parasitemia/radionuclide imaging
  • Radiopharmaceuticals/diagnostic use
  • Radiopharmaceuticals/pharmacokinetics*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Sodium Pertechnetate Tc 99m/diagnostic use
  • Sodium Pertechnetate Tc 99m/pharmacokinetics*
  • Tissue Distribution
  • Trypanosoma cruzi/physiology*

Substances:

  • Radiopharmaceuticals
  • Sodium Pertechnetate Tc 99m
8. Exp Parasitol. 2009 Dec;123(4):283-91. Epub 2008 Dec 16.

Trypanosoma cruzi: multiplex PCR to detect and classify strains according to groups I and II.

Liarte DB, Murta SM, Steindel M, Romanha AJ.

Laboratório de Parasitologia Celular e Molecular, Centro de Pesquisas René Rachou- Fiocruz, 30190-002 Belo Horizonte, Minas Gerais, Brazil. daniel@cpqrr.fiocruz.br

A multiplex PCR was developed for simultaneous detection of Trypanosoma cruzi DNA and classification of the parasite strain into groups I and II. As little as 10fg of T. cruzi DNA could be detected by multiplex PCR. The technique was shown to be specific for T. cruzi DNA, since no PCR amplification products were obtained with DNA from other tripanosomatid species. Multiplex PCR was validated by assaying genomic DNA from 34 strains of T. cruzi that had been previously characterized; 24 blood samples from experimentally-infected mice and non-infected controls; 20 buffy coat samples from patients in the acute phase of Chagas disease and non-infected individuals, and 15 samples of feces from naturally-infected Triatoma infestans. T. cruzi samples from patients and from Y strain-infected mice were classified by multiplex PCR as T. cruzi II and samples from T. infestans and Colombiana strain-infected mice as T. cruzi I.

PMID: 19133262 [PubMed - indexed for MEDLINE]
Related articles
Click here to read

Publication Types:

  • Research Support, Non-U.S. Gov't
  • Validation Studies

MeSH Terms:

  • Animals
  • Base Sequence
  • Chagas Disease/diagnosis
  • Chagas Disease/parasitology*
  • DNA, Protozoan/analysis*
  • DNA, Protozoan/chemistry
  • DNA, Protozoan/isolation & purification
  • DNA, Satellite/chemistry
  • Humans
  • Mice
  • Molecular Sequence Data
  • Phylogeny
  • Polymerase Chain Reaction/methods*
  • Repetitive Sequences, Nucleic Acid
  • Sensitivity and Specificity
  • Sequence Analysis, DNA
  • Trypanosoma cruzi/classification*
  • Trypanosoma cruzi/genetics
  • Trypanosoma cruzi/isolation & purification

Substances:

  • DNA, Protozoan
  • DNA, Satellite

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