Monday, December 7, 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 12

1. Phytother Res. 2009 Dec 3. [Epub ahead of print]

Antiprotozoal, antimycobacterial and cytotoxic potential of some british green algae.

Spavieri J, Kaiser M, Casey R, Hingley-Wilson S, Lalvani A, Blunden G, Tasdemir D.

Department of Pharmaceutical and Biological Chemistry, Centre for Pharmacognosy and Phytotherapy, School of Pharmacy, University of London, London WC1N 1AX, UK.

In the continuation of our search for natural sources for antiprotozoal and antitubercular molecules, we have screened the crude extracts of four green marine algae (Cladophora rupestris, Codium fragile ssp. tomentosoides, Ulva intestinalis and Ulva lactuca) collected from the Dorset area of England. Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Mycobacterium tuberculosis were used as test organisms in the in vitro assays. The selective toxicity of the extracts was also determined toward mammalian skeletal myoblast (L6) cells. The crude seaweed extracts had no activity against M. tuberculosis, but showed antiprotozoal activity against at least two protozoan species. All algal extracts were active against T. brucei rhodesiense, with C. rupestris being the most potent one (IC(50) value 3.7 mug/ml), whilst only C. rupestris and U. lactuca had moderate trypanocidal activity against T. cruzi (IC(50) values 80.8 and 34.9 mug/ml). Again, all four extracts showed leishmanicidal activity with IC(50) values ranging between 12.0 and 20.2 mug/ml. None of the extracts showed cytotoxicity toward L6 cells, indicating that their antiprotozoal activity is specific. This is the first study reporting antiprotozoal and antimycobacterial activity of British marine algae. Copyright (c) 2009 John Wiley & Sons, Ltd.

PMID: 19960429 [PubMed - as supplied by publisher]
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2. Planta Med. 2009 Dec 3. [Epub ahead of print]

Cytotoxic and Anti-infective Sesquiterpenes Present in Plagiochila disticha (Plagiochilaceae) and Ambrosia peruviana (Asteraceae).

Aponte JC, Yang H, Vaisberg AJ, Castillo D, Málaga E, Verástegui M, Casson LK, Stivers N, Beates PJ, Rojas R, Fernandez I, Lewis WH, Sarasara C, Sauvain M, Gilman RH, Hammond GB.

Department of Chemistry, University of Louisville, Louisville, KY, USA.

A pharmacological screening of the ethanol extract and fractions of two Peruvian medicinal plants, PLAGIOCHILA DISTICHA and AMBROSIA PERUVIANA, led to the isolation and characterization of three ENT-2,3-secoaromadendrane-type sesquiterpenoids, named plagiochiline A ( 1), I ( 2), and R ( 3), as well as of two pseudoguaianolids, damsin ( 4) and confertin ( 5), which exhibited significant cytotoxic activity against a panel of human tumor cell lines. Compounds 1, 4, and 5 were also investigated for their IN VITRO antileishmanial, trypanocidal, and antituberculosis activity against LEISHMANIA AMAZONENSIS axenic amastigotes and TRYPANOSOMA CRUZI trypomastigotes, as well as against MDR and sensitive strains of MYCOBACTERIUM TUBERCULOSIS, respectively. SUPPORTING INFORMATION available online at http://www.thieme-connect.de/ejournals/toc/plantamedica. © Georg Thieme Verlag KG Stuttgart · New York.

PMID: 19960415 [PubMed - as supplied by publisher]
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Publication Types:

  • LETTER
3. J Vector Borne Dis. 2009 Dec;46(4):303-6.

A new focus of visceral leishmaniasis in the Himalayas, India.

Raina S, Mahesh DM, Satindera KS, Gupta D, Sharma A, Thakur S.

Department of Medicine,Shimla, India.

PMID: 19959858 [PubMed - in process]
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4. J Vector Borne Dis. 2009 Dec;46(4):268-72.

Molecular detection of Leishmania infantum in naturally infected Phlebotomus perniciosus from Algarve Region, Portugal.

Maia C, Afonso MO, Neto L, Dionísio L, Campino L.

Unidade de Leishmanioses, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL);

Background & objectives: In Portugal, Phlebotomus perniciosus and P. ariasi, (Subgenus Larroussius; Diptera: Psychodidae) are the proven vectors of leishmaniasis caused by Leishmania infantum. The Algarve Region in southern Portugal has been considered an endemic focus of leishmaniasis since 1980s. The main objective of the present study was to validate a molecular approach to detect Leishmania infection in phlebotomines based on DNA extraction from the female sandfly whole body, minus genitalia, followed by PCR for application on epidemiological surveys. Methods: In Algarve Region, from early May until early November 2006, sandflies were captured by CDC miniature light-traps. kDNA-PCR and ITS1-PCR were used to screen the presence of Leishmania DNA in female sandflies after species identification by entomological keys. Results: A total of 474 sandflies were collected in 108 biotopes. One female of P. perniciosus, the predominant species, was found infected with L. infantum reflecting an overall infection rate of 0.47%. Interpretation & conclusion: PCR associated with morphological characterization of the sandflies will be a powerful epidemiological tool for the determination of the number of phlebotomines infected with Leishmania spp in nature. In addition, the simultaneous occurrence of dogs and P. perniciosus infected with L. infantum shows that Algarve continues to be an endemic focus of canine leishmaniasis. Furthermore, as P. sergenti and P. papatasi which transmit L. tropica and L. major, respectively were present, the future introduction of these two Leishmania species in southern region of Portugal should not be neglected.

PMID: 19959852 [PubMed - in process]
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5. J Vector Borne Dis. 2009 Dec;46(4):247-55.

Application of predictive degree day model for field development of sandfly vectors of visceral leishmaniasis in northwest of Iran.

Oshaghia MA, Ravasanb NM, Javadian E, Rassi Y, Sadraei J, Enayati AA, Vatandoost H, Zare Z, Emami SN.

Department of Medical Entomology and Vector Control, School of Public Health, Tehran University of Medical Sciences Tehran.

Background & objectives: Temperature plays a significant role in insect's development where a rise in temperature, accelerates the insect's metabolic rates, increases egg production and makes blood feeding more frequent. It also shortens the time period required for the development of pathogens within insects. Visceral leishmaniasis (VL) is one of the most important vector-borne diseases transmitted by different sandfly species. In this study, a phenological model was used to estimate the number of generations, peak activity and temporal variability of sandflies in the main VL foci in northwest Iran. Methods: Development requirements of different life stages of a Phlebotomus papatasi laboratory colony were measured and were subjected to the formula for calculation of accumulated degree day (ADD) for field sandflies using the online soft (UC IPM), using horizontal cut-off method and single triangle model. Sandflies population dynamics was monitored in the field during the seasonal activity in the region and its association with the ADD was tested using SAS software. Results: Populations of sandflies accommodated well with the amount of accumulated degree days (ADD) in the region. During the seasonal activity, a total of 639 ADD were produced which was enough to support one complete life cycle and growth of the next generation up to late larval instar. Larvae of the second generation hibernate through winter and the first adult population appears in the mid to late June of the next year when they receive at least 182 ADD from the beginning of the spring. The highest population density of sandflies was observed in early August, followed by a rapid decrease in early September, with the adult population disappearing completely in late September. This is the first degree day model related to sandflies in the most important VL foci of Iran. Interpretation & conclusion: Further studies in various regions with variable climate are recommended in order to better estimate and understand the development time, population dynamics and activities of the vectors which in turn could be used in proper implementation of effective vector control programmes.

PMID: 19959849 [PubMed - in process]
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6. J Parasitol. 2009 Dec 3:1. [Epub ahead of print]

ANTI-TRYPANOSOMATID ACTIVITY OF CERAGENINS.

Lara D, Feng Y, Bader J, Savage P, Maldonado R.

Cationic steroid antibiotics (CSAs) or ceragenins are amphiphilic compounds consisting of cholic acid backbone that is attached to several cationic amines. In this study, we tested the hypothesis that CSAs possess anti-parasitic activities with minimal to no effects on mammalian cells, and thus could be used as potential therapeutic agents against pathogenic trypanosomatids. To investigate this, we synthesized CSAs and determined their trypanocidal and leishmanicidal activities in vitro. The three ceragenins (i.e., CSA-8, CSA-13, and CSA-54) assayed showed several degrees of parasiticidal activity. CSA-13 was the most effective compound against Leishmania major promastigotes and Trypanosoma cruzi trypomastigotes (LD50 4.9 and 9 M, respectively). The trypanocidal activities of these ceragenins were also assessed by infectivity experiments. We found CSA-8 was more effective on T. cruzi intracellular amastigotes, when the infected host cells were treated during 24 hr (LD50 6.7 M). Macrophages and LLC-MK2 (treated for 72 hr) showed relative low susceptibility to these compounds. Our results suggest that ceragenins are indeed promising chemotherapeutic agents against trypanosomatids that need further investigation.

PMID: 19958044 [PubMed - as supplied by publisher]
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7. Phytother Res. 2009 Dec 2. [Epub ahead of print]

Screening of some Tanzanian medicinal plants for their trypanocidal and cytotoxic activities.

Nibret E, Ashour ML, Rubanza CD, Wink M.

Institut für Pharmazie und Molekulare Biotechnologie, Universität Heidelberg, Im Neuenheimer Feld 364, 69120, Heidelberg, Germany.

The objective of the present study was to evaluate in vitro antitrypanosomal and cytotoxic activities of crude extracts of 20 traditionally used medicinal plants of Tanzania. A total of 40 extracts (dichloromethane and methanol) were screened for antiproliferative activity of bloodstream form of T. b. brucei and human leukaemia HL-60 cell. Inhibition of cell proliferation was assessed using resazurin as vital stain. Of the 40 extracts tested, the dichloromethane extract from bark of Warburgia salutaris (Canellaceae) exhibited the most potent antitrypanosomal activity with an IC(50) value of 10.68 mug/ml. A dichloromethane extract from Lannea stuhlmannii (Anacardiaceae) was found to be the most cytotoxic extract against HL-60 (IC(50) = 27.15 mug/ml). Out of the 20 plants tested, 5 plants exhibited trypanocidal activity with IC(50) values below 20 mug/ml. These 5 plants: Entandrophragma bussei (Meliaceae), Securidaca longepedunculata (Polygalaceae), Warburgia salutaris (Canellaceae), Zanha africana (Sapindaceae) and Zanthoxylum chalybeum (Rutaceae) could therefore serve as sources of lead compounds for treatment of trypanosomiasis. Copyright (c) 2009 John Wiley & Sons, Ltd.

PMID: 19957246 [PubMed - as supplied by publisher]
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8. PLoS Negl Trop Dis. 2009 Dec 1;3(12):e557.

A Major Genetic Locus in Trypanosoma brucei Is a Determinant of Host Pathology.

Morrison LJ, Tait A, McLellan S, Sweeney L, Turner CM, Macleod A.

Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Biomedical Research Centre, Glasgow, United Kingdom.

The progression and variation of pathology during infections can be due to components from both host or pathogen, and/or the interaction between them. The influence of host genetic variation on disease pathology during infections with trypanosomes has been well studied in recent years, but the role of parasite genetic variation has not been extensively studied. We have shown that there is parasite strain-specific variation in the level of splenomegaly and hepatomegaly in infected mice and used a forward genetic approach to identify the parasite loci that determine this variation. This approach allowed us to dissect and identify the parasite loci that determine the complex phenotypes induced by infection. Using the available trypanosome genetic map, a major quantitative trait locus (QTL) was identified on T. brucei chromosome 3 (LOD = 7.2) that accounted for approximately two thirds of the variance observed in each of two correlated phenotypes, splenomegaly and hepatomegaly, in the infected mice (named TbOrg1). In addition, a second locus was identified that contributed to splenomegaly, hepatomegaly and reticulocytosis (TbOrg2). This is the first use of quantitative trait locus mapping in a diploid protozoan and shows that there are trypanosome genes that directly contribute to the progression of pathology during infections and, therefore, that parasite genetic variation can be a critical factor in disease outcome. The identification of parasite loci is a first step towards identifying the genes that are responsible for these important traits and shows the power of genetic analysis as a tool for dissecting complex quantitative phenotypic traits.

PMID: 19956590 [PubMed - in process]
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9. PLoS One. 2009 Dec 2;4(12):e7880.

Imm unogenicity and Efficacy of Single Antigen Gp63, Polytope and PolytopeHSP70 DNA Vaccines against Visceral Leishmaniasis in Experimental Mouse Model.

Sachdeva R, Banerjea AC, Malla N, Dubey ML.

Department of Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Polytope approach of genetic immunization is a promising strategy for the prevention of infectious disease as it is capable of generating effective cell mediated immunity by delivering the T cell epitopes assembled in series. Leishmaniasis is a significant world wide health problem for which no vaccine exists. In this study we have compared immunogenicity and efficacy of three types of DNA vaccines: single antigen Gp63 (Gp63/pcDNA), polytope (Poly/pcDNA) and Polytope fused with hsp70 (Poly/hsp/pcDNA) against visceral leishmaniasis in susceptible BALB/c mice. Mice vaccinated with these plasmids generated strong Th1 immune response as seen by dominating IFN-gamma over IL-10 cytokine. Interestingly, cytotoxic responses generated by polytope DNA plasmid fused with hsp70 of Leishmania donovani were significantly higher when compared to polytope and single antigen Gp63 vaccine. Challenge studies revealed that the parasite load in liver and spleen was significantly lower with Poly/hsp/pcDNA vaccination compared to other vaccines. Therefore, our study indicates that polytope DNA vaccine is a feasible, practical and effective approach for visceral leishmaniasis.

PMID: 19956549 [PubMed - in process]
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10. Brief Bioinform. 2009 Dec 2. [Epub ahead of print]

Detection of human interchromosomal trans-splicing in sequence databanks.

Herai RH, Yamagishi ME.

Trans-splicing is a common phenomenon in nematodes and kinetoplastids, and it has also been reported in other organisms, including humans. Up to now, all in silico strategies to find evidence of trans-splicing in humans have required that the candidate sequences follow the consensus splicing site rules (spliceosome-mediated mechanism). However, this criterion is not supported by the best human experimental evidence, which, except in a single case, do not follow canonical splicing sites. Moreover, recent findings describe a novel alternative tRNA mediated trans-splicing mechanism, which prescinds the spliceosome machinery. In order to answer the question, 'Are there hybrid mRNAs in sequence databanks, whose characteristics resemble those of the best human experimental evidence?', we have developed a methodology that successfully identified 16 hybrid mRNAs which might be instances of interchromosomal trans-splicing. Each hybrid mRNA is formed by a trans-spliced region (TSR), which was successfully mapped either onto known genes or onto a human endogenous retrovirus (HERV-K) transcript which supports their transcription. The existence of these hybrid mRNAs indicates that trans-splicing may be more widespread than believed. Furthermore, non-canonical splice site patterns suggest that infrequent splicing sites may occur under special conditions, or that an alternative trans-splicing mechanism is involved. Finally, our candidates are supposedly from normal tissue, and a recent study has reported that trans-splicing may occur not only in malignant tissues, but in normal tissues as well. Our methodology can be applied to 5'-UTR, coding sequences and 3'-UTR in order to find new candidates for a posteriori experimental confirmation.

PMID: 19955235 [PubMed - as supplied by publisher]
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