Tuesday, June 9, 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 16

1: Mol Microbiol. 2009 Jun;72(5):1100-10.Click here to read

Hypermethylated cap 4 maximizes Trypanosoma brucei translation.

Zamudio JR, Mittra B, Campbell DA, Sturm NR.

Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095-1489, USA.

Through trans-splicing of a 39-nt spliced leader (SL) onto each protein-coding transcript, mature kinetoplastid mRNA acquire a hypermethylated 5'-cap structure, but its function has been unclear. Gene deletions for three Trypanosoma brucei cap 2'-O-ribose methyltransferases, TbMTr1, TbMTr2 and TbMTr3, reveal distinct roles for four 2'-O-methylated nucleotides. Elimination of individual gene pairs yields viable cells; however, attempts at double knock-outs resulted in the generation of a TbMTr2-/-/TbMTr3-/- cell line only. Absence of both kinetoplastid-specific enzymes in TbMTr2-/-/TbMTr3-/- lines yielded substrate SL RNA and mRNA with cap 1. TbMTr1-/- translation is comparable with wildtype, while cap 3 and cap 4 loss reduced translation rates, exacerbated by the additional loss of cap 2. TbMTr1-/- and TbMTr2-/-/TbMTr3-/- lines grow to lower densities under normal culture conditions relative to wildtype cells, with growth rate differences apparent under low serum conditions. Cell viability may not tolerate delays at both the nucleolar Sm-independent and nucleoplasmic Sm-dependent stages of SL RNA maturation combined with reduced rates of translation. A minimal level of mRNA cap ribose methylation is essential for trypanosome viability, providing the first functional role for the cap 4.

PMID: 19504740 [PubMed - in process]

2: An Bras Dermatol. 2009 Mar-Apr;84(2):125-8.Click here to read

[The use of azythromycin and N-methyl glucamine for the treatment of cutaneous Leishmaniasis caused by Leishmania (Leishmania) amazonensis in C57BL6 mice.]

[Article in Portuguese]

Sampaio RN, Lucas IC, Costa Filho AV.

Universidade de Brasília.

BACKGROUND: The first choice treatment for cutaneous Leishmaniasis is N-methyl glucamine: it has high toxicity, requires parenteral administration and cure is not always reached. Azythromycin showed in vitro action and controversial results in humans with the disease. OBJECTIVE: To verify if the association of N-methyl-glucamine - azythromycin is more effective than N-methyl-glucamine alone for the treatment of experimental Leishmaniasis. METHODS: Twenty-five C57BL/6 mice were inoculated with L. (L.) amazonensis strain and divided into two groups. One group was treated with 400mgSbV/kg/day of N-methyl glucamine and 200mg/kg/day of azythromycin for 20 days and the other group received the same dose of N-methyl glucamine alone during the same period of time. Clinical and parasitological evaluations were submitted to statistical analyses. RESULTS: There was no statistical difference in clinical analysis, in amastigotes investigation and in cultures. There were significant differences in cultures using limiting dilution, which showed lower efficacy of the association N-methyl glucamine -azythromycin. CONCLUSION: N-methyl glucamine-azythromycin association was not more effective than N-methyl glucamine alone.

PMID: 19503979 [PubMed - in process]

3: Cad Saude Publica. 2009 Jun;25(6):1325-36.Click here to read

[Epidemiology of American tegumentary leishmaniasis in the State of Acre, Brazilian Amazon.]

[Article in Portuguese]

Silva NS, Muniz VD.

Instituto de Ciências Biomédicas, Universidade de São Paulo.

This was a descriptive statistical study of 8,516 cases of American tegumentary leishmaniasis in the State of Acre, Brazil, from 2001 to 2006 (second period), comparing the results to a previous publication with data from the same State for 1992 to 1997 (first period). Prevalence in the State more than doubled (55.7/10,000 inhabitants from 1992 to 1997 and 128.5/10,000 inhabitants from 2001 to 2006). Males predominated (68.8%, n = 5,860) in the second period. Mean age in the second period was 26.3 years, slightly lower than in the first. Individuals with low schooling were more affected by the disease. The other variables were area of residence, occupation, diagnostic criterion, clinical form, treatment, relapse, time before seeking treatment, and evolution. In conclusion, American tegumentary leishmaniasis epidemiological indicators worsened in the State between the two periods.

PMID: 19503963 [PubMed - in process]

4: PLoS ONE. 2009 Jun 5;4(6):e5820.Click here to read

Identification of Novel Leishmania donovani Antigens that Help Define Correlates of Vaccine-Mediated Protection in Visceral Leishmaniasis.

Bhowmick S, Ali N.

Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Kolkata, West Bengal, India.

Visceral leishmaniasis (VL), caused by the intracellular parasite Leishmania donovani is a major public health problem in the developing world. But there is no effective and safe vaccine approved for clinical use against any form of leishmaniasis. Through reactivity with kala-azar patient and cured sera, polypeptides ranging from 91 to 31-kDa from L. donovani promastigotes were previously identified as potential protective vaccine candidates. In this study four polypeptides 91(LD91), 72 (LD72), 51(LD51) and 31 (LD31)-kDa were purified using sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by electroelution. We compared the vaccine efficacy of these antigens encapsulated in cationic liposomes in BALB/c mice against challenge infection with L. donovani. Our results demonstrated that liposomal LD31 (74%-77%) and LD51 (72%-75%) vaccination reduced parasite burden to the greatest degree followed by liposomal LD72 (65%-67%) and LD91 (46%-49%). Analysis of the cytokine responses in immunized mice revealed that all the vaccinated groups produced prechallenge interferon-gamma, interleukin-12 and interleukin-4. Interestingly, the degree of reduction in parasite load could be predicted by the magnitude of the cytokine responses which correlated inversely with the parasite burden both in liver and spleen. The 31, 51 and 72-kDa bands were identified as ATP synthase alpha chain, beta-tubulin and heat shock 70-related protein 1 precursor of L. major, respectively using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF/TOF) mass spectrometry. These three leishmanial antigens have not been described before as successful vaccine candidates examined against in vivo VL model. Thus, these antigens can be potential components of future antileishmaniasis vaccines.

PMID: 19503834 [PubMed - in process]

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5: PLoS Pathog. 2009 Jun;5(6):e1000468. Epub 2009 Jun 5.Click here to read

The Glycosylphosphatidylinositol-PLC in Trypanosoma brucei Forms a Linear Array on the Exterior of the Flagellar Membrane Before and After Activation.

Hanrahan O, Webb H, O'Byrne R, Brabazon E, Treumann A, Sunter JD, Carrington M, Voorheis HP.

School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.

Bloodstream forms of Trypanosoma brucei contain a glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC) that cleaves the GPI-anchor of the variable surface glycoprotein (VSG). Its location in trypanosomes has been controversial. Here, using confocal microscopy and surface labelling techniques, we show that the GPI-PLC is located exclusively in a linear array on the outside of the flagellar membrane, close to the flagellar attachment zone, but does not co-localize with the flagellar attachment zone protein, FAZ1. Consequently, the GPI-PLC and the VSG occupy the same plasma membrane leaflet, which resolves the topological problem associated with the cleavage reaction if the VSG and the GPI-PLC were on opposite sides of the membrane. The exterior location requires the enzyme to be tightly regulated to prevent VSG release under basal conditions. During stimulated VSG release in intact cells, the GPI-PLC did not change location, suggesting that the release mechanism involves lateral diffusion of the VSG in the plane of the membrane to the fixed position of the GPI-PLC.

PMID: 19503825 [PubMed - in process]

6: J Vector Borne Dis. 2009 Jun;46(2):136-40.

The sandflies of the Satluj river valley, Himachal Pradesh (India): some possible vectors of the parasite causing human cutaneous and visceral leishmaniases in this endemic focus.

Sharma NL, Mahajan VK, Ranjan N, Verma GK, Negi AK, Mehta KI.

Department of Dermatology, Venereology & Leprosy, Indira Gandhi Medical College, Shimla, India.

Background & objectives: The recently recognized endemic focus of leishmaniasis in Satluj river valley in Himachal Pradesh (India) lies in north-western Himalayas (30 degrees N, 70 degrees E). This endemic focus of leishmaniasis appears peculiar where localized cutaneous leishmaniasis (LCL) co-exists with visceral leishmaniasis (VL), and Leishmania donovani is predominant pathogen for LCL whereas only a few cases have been due to Leishmania tropica. This study was carried out to collect sandflies, identify and delineate their habitat and role in transmission of human leishmaniasis in this endemic focus. Methods: During June 2003 to September 2007, 142 (M-22, F-120) sandflies were collected with aspirators from 10 endemic villages of Kinnaur and Shimla districts. Results & conclusion: Sixty-two of the identified sandflies caught belonged to the genus Phlebotomus species, including some species that are known to act as vectors of the parasites causing human leishmaniasis. The Phlebotomus (Adlerius) chinensis longiductus (Parrot), 1928 (28 sandflies), P. major (8 sandflies), P. (Larroussius) kandelakii burneyi (Lewis), 1967 (8 sandflies) were identified. The identification of the main species of vector sandfly in the region is complicated because it is still uncertain which Leishmania species cause(s) the local human leishmaniasis. Circumstantially it seems likely, however, that Phlebotomus (Adlerius) chinensis longiductus is the main vector. Other species found, such as P. major and P. (Larroussius) kandelakii burneyi, may also be responsible for some cases. A more elaborate study is recommended.

PMID: 19502693 [PubMed - in process]

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7: Eur J Dermatol. 2009 Jun 5. [Epub ahead of print]Click here to read

Unusual multifocal cutaneous leishmaniasis in a diabetic patient.

Ceyhan AM, Yildirim M, Basak PY, Akkaya VB.

PMID: 19502157 [PubMed - as supplied by publisher]

8: Acta Trop. 2009 Jun 4. [Epub ahead of print]Click here to read

Relationship between sand fly fauna and kala-azar endemicity in Bangladesh.

Alam MS, Wagatsuma Y, Mondal D, Khanum H, Haque R.

International Center for Diarrhoeal Disease Research Bangladesh, 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212, Bangladesh.

An entomological survey was carried out in Mymensingh district which contributes the highest incidence of visceral leishmaniasis (kala-azar) in Bangladesh. For the first time in Bangladesh CDC miniature light trap was used for indoor collection of sandflies. A total of 726 sand fly specimens belonging to nine species, one species of the genus Phlebotomus and eight species Sergentomyia genus were collected. Phlebotomus argentipes Annaandale Brunetti made up 59.2% of the total collection. Among Sergentomyia species Sergentomyia shorttii Adler & Theodor contributed 14.4% of the total collection.

PMID: 19501561 [PubMed - as supplied by publisher]

9: J Ethnopharmacol. 2009 Jun 25;123(3):504-9. Epub 2009 Feb 14.Click here to read

Anti-parasitic activity and cytotoxicity of selected medicinal plants from Kenya.

Kigondu EV, Rukunga GM, Keriko JM, Tonui WK, Gathirwa JW, Kirira PG, Irungu B, Ingonga JM, Ndiege IO.

Institute of Tropical Medicine and Infectious Diseases (ITROMID), P.O. Box 54840, Nairobi 00200, Kenya.

Indigenous rural communities in the tropics manage parasitic diseases, like malaria and leishmaniasis, using herbal drugs. The efficacy, dosage, safety and active principles of most of the herbal preparations are not known. Extracts from 6 selected plant species, used as medicinal plants by indigenous local communities in Kenya, were screened for in vitro anti-plasmodial and anti-leishmanial activity, against 2 laboratory-adapted Plasmodium falciparum isolates (D6, CQ-sensitive and W2, CQ-resistant) and Leishmania major (IDU/KE/83=NLB-144 strain), respectively. The methanol extract of Suregada zanzibariensis leaves exhibited good anti-plasmodial activity (IC(50) 4.66+/-0.22 and 1.82+/-0.07 microg/ml for D6 and W2, respectively). Similarly, the methanol extracts of Albizia coriaria (IC(50) 37.83+/-2.11 microg/ml for D6) and Aspergillus racemosus (32.63+/-2.68 and 33.95+/-2.05 microg/ml for D6 and W2, respectively) had moderate anti-plasmodial activity. Acacia tortilis (IC(50) 85.73+/-3.36 microg/ml for W2) and Albizia coriaria (IC(50) 71.17+/-3.58 microg/ml for W2) methanol extracts and Aloe nyeriensis var kedongensis (IC(50) 87.70+/-2.98 and 67.84+/-2.12 microg/ml for D6 and W2, respectively) water extract exhibited mild anti-plasmodial activity. The rest of the extracts did not exhibit any anti-plasmodial activity. Although the leishmanicidal activity of extracts were lower than for pentosam (80%), reasonable activity was observed for Aloe nyeriensis methanol (68.4+/-6.3%), Albizia coriara water (66.7+/-5.0%), Maytenus putterlickoides methanol (60.0+/-6.23%), Asparagus racemosus methanol and water (58.3+/-8.22 and 56.8+/-6.58%, respectively), Aloe nyeriensis water (53.3+/-5.1%) and Acacia tortilis water (52.9+/-6.55%) extracts at 1000 microg/ml. Leishmania major infected macrophages treated with methanol extracts of Suregada zanzibariensis and Aloe nyeriensis var kedongensis and pentostam had infection rates of 28+/-2.11, 30+/-1.22 and 40+/-3.69%, respectively at 1000 microg/ml, indicating better anti-leishmanial activity for the extracts. The methanol extract of Albizia coriara (44.0+/-3.69%) and aqueous extracts of Asparagus racemosus (42+/-3.84%) and Acacia tortilis (44+/-5.59%) had similar activity to pentosam. Multiplication indices for Leishmania major amastigotes treated with methanol extracts of Albizia coriaria, Suregada zanzibariensis and Aloe nyeriensis var kedongensis, aqueous extract of Acacia tortilis and pentosam were 28.5+/-1.43, 29.4+/-2.15, 31.1+/-2.22, 35.9+/-3.49 and 44.0+/-3.27%, respectively, at 1000 microg/ml, confirming better anti-leishmanial activity for the extracts. Aqueous extracts of Aloe nyeriensis (46.7+/-3.28%) and Albizia coriaria (47.5+/-3.21%) had similar activity level to pentosam. The plant extracts have better inhibitory activity while pentosam has better leishmanicidal activity. All extracts exhibited very low cytotoxicity (CC(50) > 500 microg/ml) against human embryonic lung fibroblast (HELF) cells. The investigations demonstrated the efficacy and safety of some extracts of plants that are used by rural indigenous communities for the treatment of parasitic diseases.

PMID: 19501282 [PubMed - in process]

10: Exp Parasitol. 2009 Jun 2. [Epub ahead of print]Click here to read

Down regulation of KMP-11 in Leishmania infantum axenic antimony resistant amastigotes as revealed by a proteomic screen.

Fadili KE, Drummelsmith J, Roy G, Jardim A, Ouellette M.

Centre de Recherche en Infectiologie du Centre de Recherche du CHUQ and Division de Microbiologie, Faculté de Médecine, Université Laval, Québec, QC, Canada.

The therapeutic mainstay against the protozoan parasite Leishmania is still based on the antiquated pentavalent antimonials, but resistance is increasing in several parts of the world. Resistance is now partly understood in laboratory promastigote isolates, but the mechanism leading to drug resistance in amastigote isolates is lagging behind. Here we describe a comparative proteomic analysis of a genetically related pair of antimonial-sensitive and -resistant Leishmania infantum axenic amastigote strains. The proteomics screen has highlighted a number of proteins differentially expressed in the resistant parasite. The expression of the protein argininosuccinate synthetase (ARGG) was increased in the drug resistant mutant while a decrease in the expression of the kinetoplastid membrane protein (KMP-11) correlated with the drug resistance phenotype. This proteomic screen highlighted several novel proteins that are putatively involved in resistance to antimonials.

PMID: 19500579 [PubMed - as supplied by publisher]

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