Friday, May 15, 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 -10 of 11

1: PLoS Negl Trop Dis. 2009;3(5):e441. Epub 2009 May 26.Click here to read

Leishmania infantum Amastigotes Enhance HIV-1 Production in Cocultures of Human Dendritic Cells and CD4 T Cells by Inducing Secretion of IL-6 and TNF-alpha.

Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, and Faculté de Médecine, Université Laval, Québec, Québec, Canada.

BACKGROUND: Visceral leishmaniasis has emerged as an important opportunistic disease among patients infected with HIV-1. Both HIV-1 and the protozoan parasite Leishmania can productively infect cells of the macrophage-dendritic cell lineage. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that Leishmania infantum amastigotes increase HIV-1 production when human primary dendritic cells (DCs) are cocultured together with autologous CD4(+) T cells. Interestingly, the promastigote form of the parasite does not modulate virus replication. Moreover, we report that amastigotes promote virus replication in both cell types. Our results indicate that this process is due to secretion of parasite-induced soluble factors by DCs. Luminex micro-beads array system analyses indicate that Leishmania infantum amastigotes induce a higher secretion of several cytokines (i.e. IL-1alpha, IL-2, IL-6, IL-10 and TNF-alpha) and chemokines (i.e. MIP-1alpha, MIP-1beta and RANTES) in these cells. Studies conducted with pentoxifylline and neutralizing antibodies revealed that the Leishmania-dependent augmentation in HIV-1 replication is due to a higher secretion of IL-6 and TNF-alpha. CONCLUSIONS/SIGNIFICANCE: Altogether these findings suggest that the presence of Leishmania within DC/T-cell conjugates leads to an enhancement of virus production and demonstrate that HIV-1 and Leishmania can establish complex interactions in such a cellular microenvironment.

PMID: 19440357 [PubMed - in process]

Patient Drug Information

  • Pentoxifylline (Pentoxil® , Trental® )

    Pentoxifylline is used to improve blood flow in patients with circulation problems to reduce aching, cramping, and tiredness in the hands and feet. It works by decreasing the thickness (viscosity) of blood. This change a...

2: Indian J Dermatol Venereol Leprol. 2009 May-Jun;75(3):330.

Facial leishmaniasis mistaken for pimples.

PMID: 19439908 [PubMed - in process]

3: Indian J Dermatol Venereol Leprol. 2009 May-Jun;75(3):279-82.

Clindamycin lotion alone versus combination lotion of clindamycin phosphate plus tretinoin versus combination lotion of clindamycin phosphate plus salicylic acid in the topical treatment of mild to moderate acne vulgaris: a randomized control trial.

Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Center for Research and Training in Skin Diseases and Leprosy, Medical Sciences/University of Tehran, Iran.

BACKGROUND: Acne vulgaris is a common skin disease that affects 85% to 100% of people at some time during their lives. It is characterized by noninflammatory follicular papules or comedones and by inflammatory papules, pustules, and nodules in its more severe forms. AIMS: To compare the efficacy of combination treatment of clindamycin+salicylic acid, versus clindamycin+tretinoin versus clindamycin alone in the treatment of the mild-to-moderate acne vulgaris. METHODS: This was a single-blinded, randomized clinical trial.Forty-two female patients (age range: 15-25 years) with mild-to-moderate acne vulgaris were selected randomly and subsequently randomized to 3 groups. Group A patients were treated with 1% clindamycin lotion (C lotion) twice daily. Group B patients were treated with 1% clindamycin+0.025% tretinoin lotion once nightly (CT lotion). Group C patients were treated with 1% clindamycin+2% salicylic acid lotion twice daily (CS lotion) for 12 weeks. For comparison of efficacy of these treatments, and regarding the skewed distribution of the data, Kruskal-Wallis Test and Mann-Whitney U test were used. SPSS software was used for statistical analysis. RESULTS: There was a significant difference between 3 types of treatment in the respect of the total lesion count (TLC) improvement (P = 0.039). The efficacy of treatment on Acne Severity Index (ASI) was maximum for CS lotion (81.80% reduction in ASI). CT lotion reduced ASI by as much as 73.73% during 12 weeks of treatment. The efficacy of C lotion was calculated to be 37.87% in the reduction of ASI. CONCLUSIONS: Our data suggested that the efficacy of CS lotion was significantly more than C lotion with respect to the TLC and ASI, although there was no significant difference between CS and CT lotion.

PMID: 19439881 [PubMed - in process]

Patient Drug Information

  • Tretinoin (Vesanoid® )

    Tretinoin is used to treat acute promyelocytic leukemia (APL; a type of cancer in which there are too many immature blood cells in the blood and bone marrow) in people who have not been helped by other types of chemother...

  • Clindamycin (Cleocin® )

    Clindamycin is used to treat certain types of bacterial infections, including infections of the lungs, skin, blood, female reproductive organs, and internal organs. Clindamycin is in a class of medications called lincomy...

  • Tretinoin Topical (Avita® , Renova® Emollient, Retin-A® , ...)

    Tretinoin is used to treat acne. It promotes peeling of affected skin areas and unclogs pores. Tretinoin controls acne but does not cure it.

  • » See all 5 drug reports ...
4: J Biol Chem. 2009 May 13. [Epub ahead of print]Click here to read

Arginine homeostasis and transport in the human pathogen Leishmania donovani.

Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000.

Arginine is an essential amino acid for the human pathogen Leishmania, but not to its host. Thus, the mechanism by which this protozoan parasite regulates cellular homeostasis of arginine is critical for its survival and virulence. In a previous study, we cloned and functionally characterized a high affinity arginine-specific transporter, LdAAP3, from L. donovani. In this investigation, we have characterized the relationship between arginine transport via LdAAP3 and amino acid availability. Starving promastigotes for amino acids decreased the cellular level of most amino acids including arginine but also increased the abundance of both LdAAP3 mRNA and protein and up-regulated arginine transport activity. Genetic obliteration of the polyamine biosynthesis pathway for which arginine is the sole precursor caused a significant decrease in the rate of arginine transport. Cumulatively, we established that LdAAP3 expression and activity changed whenever the cellular level of arginine changed. Our findings have led to the hypothesis that L. donovani promastigotes have a signaling pathway that senses cellular concentrations of arginine and subsequently activates a mechanism that regulates LdAAP3 expression and activity. Interestingly, this response of LdAAP3 to amino acid availability in L. donovani is identical to that of the mammalian cation amino acid transporter 1 (CAT1). Thus, we conjecture that Leishmania mimics the host response to amino acid availability in order to improve virulence.

PMID: 19439418 [PubMed - as supplied by publisher]

5: Microbes Infect. 2009 May 8. [Epub ahead of print]Click here to read

Modulation of P2X(7) purinergic receptor in macrophages by Leishmania amazonensis and its role in parasite elimination.

Laboratory of Immunopharmacology, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373. 21941-902 Rio de Janeiro- Brazil; Laboratory of Immunophysiology, Instituto de Biofisica Carlos Chagas Filho Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373. 21941-902 Rio de Janeiro- Brazil.

The purinergic P2X(7) receptor is a membrane protein of leucocytes involved in the clearance of intracellular bacteria such as Chlamydia and Mycobacterium. In this work, we investigated the role and modulation of macrophage P2X(7)R by the intracellular infection with the protozoan parasite Leishmania amazonensis. Upon infection, isolated murine macrophages displayed enhanced expression of P2X(7)R and were significantly more responsive to extracellular ATP (ATPe) -induced pore opening, as demonstrated by the increased uptake of Lucifer Yellow. This was extended to the in vivo situation, where cells from established cutaneous lesions were more sensitive to ATPe than cells from uninfected mice. ATP treatment of infected macrophages inhibited parasite growth, and this was prevented by pre-treatment with oxidized ATP, a selective antagonist of P2X(7)R. Parasite killing was unlikely due to induction of nitric oxide production or cytolysis of infected macrophage, as those functions were unaltered with parasite-effective ATPe concentrations. A direct drug effect is also unlike, as ATPe enhanced axenic parasite growth. We found that leishmanial infection rendered wild-type but not P2X(7)R-deficient macrophages more prone to ATP-induced apoptosis.These results show that macrophage infection with L. amazonensis leads to enhanced expression of functional P2X(7)R, that upon ligation with ATPe helps in the elimination of the parasites by an as yet unclear mechanism possibly involving host cell apoptosis.

PMID: 19439191 [PubMed - as supplied by publisher]

6: Br J Dermatol. 2009 Apr 29. [Epub ahead of print]Click here to read

Presentation of leishmaniasis (Leishmania infantum) in the skin of a patient with severe atopic dermatitis.

Infectious Diseases.

PMID: 19438451 [PubMed - as supplied by publisher]

7: Clin Vaccine Immunol. 2009 Apr;16(4):515-20. Epub 2009 Feb 11.Click here to read LinkOut

Lateral flow immunoassay for diagnosis of Trypanosoma cruzi infection with high correlation to the radioimmunoprecipitation assay.

InBios International, Inc., Seattle, WA 98104, USA. raymond@inbios.com

The incidence of blood donors seropositive for Trypanosoma cruzi in North America has increased with population migration and more rigorous surveillance. The United States, considered nonendemic for T. cruzi, could therefore be at risk to exposure to parasite transmission through blood or organ donations. Current tests show variable reactivity, especially with Central American sera. Here we describe the development of a lateral flow immunoassay for the rapid detection of T. cruzi infection that has a strong correlation to the radioimmunoprecipitation assay (RIPA) "gold standard" in the United States. Such a test could have utility in small blood banks for prescreening donors, as well as in cardiac transplantation evaluation. T. cruzi consensus and/or RIPA-positive sera from Central and South America were evaluated in enzyme immunoassays (EIAs). These included commercial panels from Boston Biomedica, Inc. (BBI) (n = 14), and HemaBio (n = 21). Other sources included RIPA-positive sera from the American Red Cross (ARC) (n = 42), as well as from Chile. Sera were tested with the multiepitope recombinant TcF. All but one of the BBI samples were positive and 7 of 21 HemaBio samples and 6 of 42 ARC samples were low positive or negative. This observation indicated the need for additional antigens. To complement TcF reactivity, we tested the sera with peptides 30, 36, SAPA, and 1.1, 1.2, and 1.3 His fragments of 85-kDa trans-sialidase. We identified a promising combination of the tested antigens and constructed a single recombinant protein, ITC6, that enhanced the relative sensitivity in U.S. blood donor sera compared to that of TcF. The data on its evaluation using RIPA-confirmed positive sera in EIA and lateral flow immunoassay studies are presented, along with an additional recombinant protein, ITC8.2, with two additional sequences for peptide 1 and Kmp-11. The latter, when evaluated in a dipstick assay with consensus positive sera, had a sensitivity of 99.2% and a specificity of 99.1%.

PMID: 19211772 [PubMed - indexed for MEDLINE]

PMCID: PMC2668284 [Available on 2009/10/01]

8: Int J Exp Pathol. 2009 Feb;90(1):52-7.Click here to read LinkOut

Trypanosoma cruzi and myoid cells from seminiferous tubules: interaction and relation with fibrous components of extracellular matrix in experimental Chagas' disease.

Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.

The main transmission route of Trypanosoma cruzi is by triatomine bugs. However, T. cruzi is also transmitted through blood transfusion, organ transplantation, ingestion of contaminated food or fluids, or is congenital. Sexual transmission, although suggested since the discovery of Chagas' disease, has remained unproven. Sexual transmission would require T. cruzi to be located at the testes and ovaries. Here we investigated whether T. cruzi is present in the gonads of mice infected with 10(4) T. cruzi trypomastigotes from the CL strain. Fourteen days after experimental infection, histopathological examination showed alterations in the extracellular matrix of the lamina propria of the seminiferous tubules. Furthermore, amastigotes were present in seminiferous tubules, within myoid cells, and in the adjacencies of the basal compartment. These results indicate that T. cruzi is able to reach seminiferous tubule lumen, thus suggesting that Chagas' disease could potentially be transmitted through sexual intercourse. Complementary studies are required to demonstrate that Chagas' disease can be transmitted by coitus.

PMID: 19200251 [PubMed - indexed for MEDLINE]

9: Acta Trop. 2009 May-Jun;110(2-3):137-47. Epub 2008 Oct 15.Click here to read LinkOut

Triatominae-Trypanosoma cruzi/T. rangeli: Vector-parasite interactions.

Universidad del Tolima, Barrio Santa Helena, Ibagué, Colombia. gvallejo@ut.edu.co

Of the currently known 140 species in the family Reduviidae, subfamily Triatominae, those which are most important as vectors of the aetiologic agent of Chagas disease, Trypanosoma cruzi, belong to the tribes Triatomini and Rhodniini. The latter not only transmit T. cruzi but also Trypanosoma rangeli, which is considered apathogenic for the mammalian host but can be pathogenic for the vectors. Using different molecular methods, two main lineages of T. cruzi have been classified, T. cruzi I and T. cruzi II. Within T. cruzi II, five subdivisions are recognized, T. cruzi IIa-IIe, according to the variability of the ribosomal subunits 24Salpha rRNA and 18S rRNA. In T. rangeli, differences in the organization of the kinetoplast DNA separate two forms denoted T. rangeli KP1+ and KP1-, although differences in the intergenic mini-exon gene and of the small subunit rRNA (SSU rRNA) suggest four subpopulations denoted T. rangeli A, B, C and D. The interactions of these subpopulations of the trypanosomes with different species and populations of Triatominae determine the epidemiology of the human-infecting trypanosomes in Latin America. Often, specific subpopulations of the trypanosomes are transmitted by specific vectors in a particular geographic area. Studies centered on trypanosome-triatomine interaction may allow identification of co-evolutionary processes, which, in turn, could consolidate hypotheses of the evolution and the distribution of T. cruzi/T. rangeli-vectors in America, and they may help to identify the mechanisms that either facilitate or impede the transmission of the parasites in different vector species. Such mechanisms seem to involve intestinal bacteria, especially the symbionts which are needed by the triatomines to complete nymphal development and to produce eggs. Development of the symbionts is regulated by the vector. T. cruzi and T. rangeli interfere with this system and induce the production of antibacterial substances. Whereas T. cruzi is only subpathogenic for the insect host, T. rangeli strongly affects species of the genus Rhodnius and this pathogenicity seems based on a reduction of the number of symbionts.

PMID: 18992212 [PubMed - indexed for MEDLINE]

10: Int J Parasitol. 2008 Oct;38(12):1383-9. Epub 2008 Jul 24.Click here to read LinkOut

Sequences involved in mRNA processing in Trypanosoma cruzi.

Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

Gene expression in Trypanosomatids requires processing of polycistronic transcripts to generate monocistronic mRNAs by cleavage events that are coupled to the addition of a Spliced Leader sequence (SL) at the 5'-end and a poly(A) tail at the 3'-end of each mRNA. Here we investigate the sequence requirements involved in Trypanosoma cruzi mRNA processing by mapping all available expressed sequence tags and cDNAs containing poly(A) tail and/or SL to genomic intergenic regions. Amongst other parameters, we determined that the median lengths of 5' untranslated region (UTR) and 3'UTR sequences are 35 and 264 nucleotides, respectively; and that the median distance between SL addition sites and a polypyrimidine motif is 18 nucleotides, whereas the median distance between poly(A) addition sites and the closest polypyrimidine-rich sequence is 40 nucleotides.

PMID: 18700146 [PubMed - indexed for MEDLINE]

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