Thursday, October 8, 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 -6 of 6

1: J Biol Chem. 2009 Oct 5. [Epub ahead of print]

Predictive computational models of substrate binding by a nucleoside transporter.

Collar CJ, Al-Salabi MI, Stewart ML, Barrett MP, Wilson WD, de Koning HP.

Georgia State University, United States;

Transporters play a vital role in both the resistance mechanisms of existing drugs and effective targeting of their replacements. Melarsoprol and diamidine compounds similar to pentamidine and furamidine are primarily taken up by trypanosomes of the genus Trypanosoma brucei through the P2 aminopurine transporter. In standardized competition experiments with [3H]-adenosine, P2 transporter inhibition constants (Ki) have been determined for a diverse dataset of adenosine analogs, diamidines, FDA approved compounds and analogs thereof, and custom designed trypanocidal compounds. Computational biology has been employed to investigate compound structure diversity in relation to P2 transporter interaction. These explorations have led to models for inhibition predictions of known and novel compounds in order to obtain information about the molecular basis for P2 transporter inhibition. A common pharmacophore for P2 transporter inhibition has been identified along with other key structural charisteristics. Our model provides insight into P2 transporter interactions with known compounds and contributes to strategies for the design of novel antiparasitic compounds. This approach offers a quantitative and predictive tool for molecular recognition by specific transporters without the need for structural or even primary sequence information of the transport protein.

PMID: 19808668 [PubMed - as supplied by publisher]

2: Trop Med Int Health. 2009 Oct 5. [Epub ahead of print]

Cerebrospinal fluid B lymphocyte identification for diagnosis and follow-up in human African trypanosomiasis in the field.

Bouteille B, Mpandzou G, Cespuglio R, Ngampo S, Peeling RW, Vincendeau P, Buguet A.

Laboratory of Parasitology, EA 3174, Faculty of Medicine, University of Limoges, France.

Summary Objectives In human African trypanosomiasis (HAT, sleeping sickness), staging of disease and treatment follow-up relies on white cell count in the cerebrospinal fluid (CSF). As B lymphocytes (CD19 positive cells) are not found in the CSF of healthy individuals but occur in neurological disorders such as multiple sclerosis, B lymphocyte count may be useful for field diagnosis/staging and therapeutic follow-up in HAT. Methods Seventy-one HAT patients were diagnosed and 50 were followed-up 6-24 months after treatment. White cell counts were used for conventional staging (stage 1, </=5 cells/mul CSF, n = 42; stage 2, >/=20 cells/mul, n = 16) and intermediate stage (6-19 cells/mul, n = 13). Slides containing 1 mul of CSF mixed with Dynabeads((R)) CD19 pan B were examined microscopically to detect B cell rosettes (bound to at least four beads). Results Stage 1 patients exhibited zero (n = 37) or one CSF rosette/mul (n = 5), contrary to most stage 2 patients (14/16: >/=2 rosettes/mul). Intermediate stage patients expressed 0 (n = 9), 1 (n = 3) or 2 (n = 1) rosettes/mul of CSF. During follow-up, rosette counts correlated with white cell count staging but were much easier to read. Conclusion B cell rosettes being easily detected in the CSF in field conditions may be proposed to replace white cell count for defining HAT stages 1 and 2 and limit uncertainty in treatment decision in patients with intermediate stage.

PMID: 19807900 [PubMed - as supplied by publisher]

3: Trop Med Int Health. 2009 Oct 5. [Epub ahead of print]

Shifting priorities in vector biology to improve control of vector-borne disease.

Lambrechts L, Knox TB, Wong J, Liebman KA, Albright RG, Stoddard ST.

Department of Entomology, University of California, Davis, CA, USA.

Summary Vector control remains the primary measure available to prevent pathogen transmission for the most devastating vector-borne diseases (VBDs): malaria, dengue, trypanosomiasis, filariasis, leishmaniasis, and Chagas disease. Current control strategies, however, are proving insufficient and the remarkable advances in the molecular biology of disease vectors over the last two decades have yet to result in tangible tools that effectively reduce VBD incidence. Here we argue that vector biologists must fundamentally shift their approach to VBD research. We propose an agenda highlighting the most critical avenues to improve the effectiveness of vector control. Research priorities must be diversified to support simultaneous development of multiple, alternative control strategies. Knowledge across relevant diseases and disciplines should be better integrated and disease prevention efforts extended beyond the academic sector to involve private industry, ministries of health, and local communities. To obtain information of more immediate significance to public health, the research focus must shift from laboratory models to natural pathogen-transmission systems. Identification and characterization of heterogeneities inherent to VBD systems should be prioritised to allow development of local, adaptive control strategies that efficiently make use of limited resources. Importantly, increased involvement of disease-endemic country (DEC) scientists, institutes, and communities will be key to enhance and sustain the fight against VBD.

PMID: 19807899 [PubMed - as supplied by publisher]

4: FEMS Immunol Med Microbiol. 2009 Sep 7. [Epub ahead of print]

Deciphering the Leishmania exoproteome: what we know and what we can learn.

Corrales RM, Sereno D, Mathieu-Daudé F.

Département Sociétés et Santé, UR016 Caractérisation et Contrôle des Populations de Vecteurs, Institut de Recherche pour le Développement, Montpellier, France.

Abstract Parasitic protozoa of the genus Leishmania are the causative agents of leishmaniasis. Survival and transmission of these parasites in their different hosts require membrane-bound or extracellular factors to interact with and modify their host environments. Over the last decade, several approaches have been applied to study all the extracellular proteins exported by an organism at a particular time or stage in its life cycle and under defined conditions, collectively termed the secretome or the exoproteome. In this review, we focus on emerging data shedding light on the secretion mechanisms involved in the production of the Leishmania exoproteome. We also describe other methodologies currently available that could be used to analyse the Leishmania exoproteome. Understanding the complexity of the Leishmania exoproteome is a key component to elucidating the mechanisms used by these parasites for exporting proteins to the extracellular space during its life cycle. Given the importance of extracellular factors, a detailed knowledge of the Leishmania exoproteome may provide novel targets for rational drug design and/or a source of antigens for vaccine development.

PMID: 19807787 [PubMed - as supplied by publisher]

5: Rev Chilena Infectol. 2008 Oct;25(5):384-9, discussion 387. Epub 2008 Oct 1.Click here to read LinkOut

[Part VI. Antiparasitic treatment for Chagas disease]

[Article in Spanish]

B WA, G IH, L MI, M LJ, V PM, H IN, V AM, P JS, H MT, A IZ.

Comité de Parasitología, Departamento de Enfermedades Emergentes y Re-emergentes, Ministerio de Salud, Chile.

As expert consensus has been arisen about universal antiparasitic treatment for all patients infected with Trypanosoma cruzi, most important drugs licensed for Chagas disease treatment are reviewed: nifurtimox and benznidazol, their mechanisms of action, doses, treatment schedules, adverse effects and contraindications. Two other drugs used for Chagas disease treatment, for which a Chilean experience may be exhibited, are allopurinol and itraconazole. Indications for treatment of Chagas disease in immunocompetent patients and immunocompromised hosts are detailed. This chapter refers besides to the evaluation and monitoring of antiparasitic therapy in immunocompromised patients, the availability of drugs and includes various forms facsimiles suggested to perform clinical and laboratory follow up of patients that undergo treatment, indicating the prescribed drug, adverse effects and time of follow up.

PMID: 18949153 [PubMed - indexed for MEDLINE]

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6: Rev Chilena Infectol. 2008 Oct;25(5):380-3. Epub 2008 Oct 1.Click here to read LinkOut

[Part V. Laboratory diagnosis of Chagas disease]

[Article in Spanish]

Apt B W, Heitmann G I, Jercic L MI, Jofré M L, Muñoz C Del V P, Noemí H I, San Martín V AM, Sapunar P J, Torres H M, Zulantay A I.

Comité de Parasitología, Departamento de Enfermedades Emergentes y Re-emergentes, Ministerio de Salud, Chile.

In this fifth part of Guidelines for Chagas disease, diagnostic techniques for Trypanosoma cruzi infection in humans are reviewed, the interpretation of laboratory results and an algorithm for laboratory diagnosis in immunocompetent hosts are presented. Chagas disease may be diagnosed by three kinds of techniques: direct, which allow detect the presence of the parasite in different kind of samples; indirect, based on the search of immune specific response against T. cruzi antigens and molecular, which detect parasite genetic material. Direct techniques are utilized mainly in acute phase of disease, as the parasite is present in blood of infected host. These techniques do not require be confirmed by other methods. For chronic undetermined phase and for symptomatic phase it is recommended to use indirect techniques; generally, immunoassay techniques (ELISA) that detect IgG antibodies directed against T. cruzi antigens are performed. As false positive results are possible, a positive or undetermined result must be confirmed by at least another technique (indirect immunofluorescence or indirect hemmaglutination). In Chile, confirmation of infection is performed by the Instituto de Salud Pública National Reference Laboratory or at surrogate centers. Molecular methods may be used to make the diagnosis in acute or chronic phase of infection, with more accuracy in the acute phase, and it is mainly recommended to diagnose vertical transmission of T. cruzi as early diagnosis of congenital infection increases the possibility to cure the sibling and besides it is a good marker to evaluate the effectiveness of treatment.

PMID: 18949152 [PubMed - indexed for MEDLINE]

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