Thursday, September 3, 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: Korean J Parasitol. 2009 Sep;47(3):213-8. Epub 2009 Aug 28.

A novel organotellurium compound (RT-01) as a new antileishmanial agent.

Lima CB, Arrais-Silva WW, Cunha RL, Giorgio S.

Department of Parasitology, Biology Institute, Universidade Estadual de Campinas, SP, Brazil.

Leishmaniasis is a neglected disease and endemic in developing countries. A lack of adequate and definitive chemotherapeutic agents to fight against this infection has led to the investigation of numerous compounds. The aim of this study was to investigate the effect of RT-01, an organotellurane compound presenting biological activities, in 2 experimental systems against Leishmania amazonensis. The in vitro system consisted of promastigotes and amastigotes forms of the parasite, and the in vivo system consisted of L. amazonensis infected BALB/c mice, an extremely susceptible mouse strain. The compound proved to be toxic against promastigotes and amastigotes. The study also showed that treatment with RT-01 produces an effect similar to that treatment with the reference antimonial drug, Glucantime, in L. amazonensis infected mice. The best results were obtained following RT-01 intralesional administration (720 microg/kg/day); mice showed significant delay in the development of cutaneous lesions and decreased numbers of parasites obtained from the lesions. Significant differences in tissue pathology consisted mainly of no expressive accumulation of inflammatory cells and well-preserved structures in the skin tissue of RT-01-treated mice compared with expressive infiltration of infected cells replacing the skin tissue in lesions of untreated mice. These findings highlight the fact that the apparent potency of organotellurane compounds, together with their relatively simple structure, may represent a new avenue for the development of novel drugs to combat parasitic diseases.

PMID: 19724693 [PubMed - in process]

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2: Korean J Parasitol. 2009 Sep;47(3):197-204. Epub 2009 Aug 28.

Trypanosome glycosylphosphatidylinositol biosynthesis.

Hong Y, Kinoshita T.

Department of Parasitology, Kyungpook National University School of Medicine, Daegu, Korea. ychong@knu.ac.kr

Trypanosoma brucei, a protozoan parasite, causes sleeping sickness in humans and Nagana disease in domestic animals in central Africa. The trypanosome surface is extensively covered by glycosylphosphatidylinositol (GPI)-anchored proteins known as variant surface glycoproteins and procyclins. GPI anchoring is suggested to be important for trypanosome survival and establishment of infection. Trypanosomes are not only pathogenically important, but also constitute a useful model for elucidating the GPI biosynthesis pathway. This review focuses on the trypanosome GPI biosynthesis pathway. Studies on GPI that will be described indicate the potential for the design of drugs that specifically inhibit trypanosome GPI biosynthesis.

PMID: 19724691 [PubMed - in process]

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3: J Vector Borne Dis. 2009 Sep;46(3):225-9.

A report on the indoor residual spraying (IRS) in the control of Phlebotomus argentipes, the vector of visceral leishmaniasis in Bihar (India): an initiative towards total elimination targeting 2015 (Series-1).

Kumar V, Kesari S, Dinesh DS, Tiwari AK, Kumar AJ, Kumar R, Singh VP, Das P.

Rajendra Memorial Research Institute of Medical Sciences, Patna,india.

Background & objectives: Visceral leishmaniasis, commonly known as kala-azar is endemic in Bihar state, India. Current vector control programme in Bihar focuses mainly on spraying the sandfly infested dwellings with DDT. The Government of India in collaboration with WHO has fixed the target 2015 for total elimination of kala-azar. The present study was carried out to see the impact of DDT and improved IEC in the containment of vector density vis-à-vis disease transmission. Methods: Before the start of the spraying operations training was imparted to all the medical and paramedical personnel regarding the methods of spraying operations. Pre- and post-sandfly density was monitored in four selected districts. Incidences of kala-azar cases were compared for pre- and post-spray periods. Social acceptability and perceptions of households was collected through questionnaires from 500 randomly selected households in the study districts. Results: House index in three study districts reduced considerably during post-spray when compared to pre-spray. Kala-azar incidence in many districts was reduced after the DDT spray. Either partial or complete refusal was reported in 14.4%, while 35% were not satisfied with the suspension concentration and coverage; and 46.6% were found satisfied with the spraying procedure. Interpretation & conclusion: Strengthening the IEC activities to sensitise the community, proper training of health personnel, monitoring of spray, good surveillance, proper treatment of cases and two rounds of DDT spray with good coverage in the endemic districts up to three years are essential to achieve the desired total elimination of kala-azar in Bihar state.

PMID: 19724087 [PubMed - in process]

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4: J Vector Borne Dis. 2009 Sep;46(3):191-6.

Comparative attractiveness of CO2-baited CDC light traps and animal baits to Phlebotomus duboscqi sandflies.

Kasili S, Kutima H, Mwandawiro C, Ngumbi PM, Anjili CO.

Jomo Kenyatta University of Agriculture and Technology, Department of Zoology, Nairobi.

Background & objectives: In order to understand sandfly bionomics, vector species identification, and to develop methods for sandfly control, there is a need to sample sandflies in any particular habitat. This survey was aimed at determining the best method of sampling Phlebotomus (Phlebotomus) duboscqi (Diptera: Psychodidae) in the field. Methods: Different animal baits and CO2-baited CDC light traps were used to attract sandflies released in an insect-proof screen-house located in the sandfly's natural habitat in Marigat, Baringo district of Kenya. Results: Attraction of hungry P. duboscqi female sandflies by the goat (Capra hircis) was significantly higher than that of hamster (Mesocricetus auretus), Nile grass rat (Arvicanthis niloticus), gerbil (Tatera robusta) and chicken (Gallus domestica). However, two rodent species, A. niloticus and T. robusta did not differ significantly. A linear regression analysis of weights of animal baits and number of sandflies attracted revealed an insignificant result. The fluorescent dyes used to distinguish sandflies of different day experiments seemed not to influence the sandfly numbers in relation to the studied sandfly behaviour. Interpretation & conclusion: The similar attraction pattern of P. duboscqi in semi-field environment by CO2-baited CDC light trap and the goat provides hope for solution to the problem of fast dissipating dry ice (CO2 source) in the field. Goats can, therefore, also be utilized as deflectors of vectors of cutaneous leishmaniasis from humans in zooprophylaxis in Leishmania major endemic areas where the sandfly is found.

PMID: 19724082 [PubMed - in process]

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5: Mol Biochem Parasitol. 2009 Aug 29. [Epub ahead of print]

The selenoproteome is dispensable in bloodstream forms of Trypanosoma brucei.

Aeby E, Seidel V, Schneider A.

Department of Chemistry and Biochemistry, University of Bern, Freiestr. 3, CH-3012 Bern, Switzerland.

Here we show that absence of Sep-tRNA:Sec-tRNA synthase (SepSecS) a key enzyme required for the synthesis of the three trypanosomal selenoproteins does not affect growth of bloodstream forms of Trypanosoma brucei. Both life cycle stages of T. brucei are highly sensitive to auranofin, a compound known to target selenoproteins. However, the same sensitivity is observed in the SepSecS double knockout cell lines indicating that the trypanocidal action of auranofin is not connected to selenoproteins. Finally, we show that absence of selenoproteins does not increase sensitivity to H(2)O(2)-induced oxidative stress. Thus in cell culture normal growth of procyclic and bloodstream T. brucei does not depend on selenoproteins.

PMID: 19723543 [PubMed - as supplied by publisher]

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Patient Drug Information

  • Auranofin (Ridaura®)

    Auranofin is used, with rest and nondrug therapy, to treat rheumatoid arthritis. It improves arthritis symptoms including painful or tender and swollen joints and morning stiffness.

  • Source: AHFS Consumer Medication Information
6: Exp Parasitol. 2009 Aug 29. [Epub ahead of print]

Leishmania infantum: Antiproliferative effect of recombinant plant cystatins on promastigotes and intracellular amastigotes estimated by direct counting and real-time pcr.

Ordóñez L, Martínez M, Rubio-Somoza I, Díaz I, Mendez S, Alunda JM.

Department of Animal Health, Faculty of Veterinary Medicine, University Complutense of Madrid, 28040 Madrid, Spain.

Two recombinant barley cystatins, HvCPI5 and HvCPI6, have been tested in vitro against promastigotes and intracellular amastigotes of Leishmania infantum in the J774 monocytic cell line. Toxicity of cystatins for J774 cells was also determined. In addition, a comparison between direct counts of intracellular amastigotes and quantitation of burden by Q-PCR was carried out. Low concentrations (2 muM) from both cystatins were unable to inhibit promastigote replication. HvCPI5 was toxic for mammalian cells; 0.1 muM reduced by more than 50% the cell viability. On the contrary, HvCPI6 did not exhibit any toxicity for J774 cells up to 6 muM and inhibited the intracellular amastigote multiplication. Dose-response analysis showed that 4.8 muM HvCPI6 reduced by >90% the intracellular parasite load and had an approximate IC(50) value of 1.5 muM. Comparable results were obtained by direct counting of intracellular amastigotes and Q-PCR. Results point towards the direct inhibition of amastigote multiplication by HvCPI6 and the interest of this recombinant cystatin in the chemotherapy of leishmaniasis.

PMID: 19723520 [PubMed - as supplied by publisher]

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7: Dermatol Online J. 2009 Jun 15;15(6):5.

Two cases of primary endonasal leishmaniasis in Sardinia (Italy).

Pau M, Atzori L, Aste N, Aste N.

Dermatology Department of Cagliari University, Cagliari, Italy.

Leishmaniasis is an endemic protozoan infection in Sardinia, one of the major islands of the Mediterranean Basin. We report two cases of endonasal primary Leishmaniasis, which is a very rare event in adult men who are immunocompetent, born in, and residents of Sardinia. The diagnosis was confirmed by the presence of intra and extracellular Leishmania amastigotes in the histological smear. Isoenzymatic characterization identified Leishmania infantum zymodeme MON-111 in both cases. Laboratory and instrumental investigations excluded visceral involvement. Treatment with meglumine antimoniate (Glucantim) intralesional administration, 1 ml weekly for 4-5 weeks, led to complete resolution. The unusual location is likely a reflection an uncommon site of inoculation of the protozoa, transmitted by flying vectors. The patients were a shepherd and a farmer, respectively, both professions at high risk of infection because of their habits of sleeping outdoors under trees or in country cottages during spring and summer and exposed to sand fly bites. Although mucosal involvement and infection by Leishmania infantum, a potential cause of visceral leishmaniasis, the Sardinian patients experienced a benign disease course considering muco-cutaneous forms described in the New World. Differential diagnosis and early detection are necessary in order to start effective treatment and prevent more serious complications.

PMID: 19723479 [PubMed - in process]

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8: Future Microbiol. 2009 Sep;4:789-96.

Activity of trypanosome lytic factor: a novel component of innate immunity.

Thomson R, Samanovic M, Raper J.

Medical Parasitology, New York University Langone Medical Center, 341 East 25th Street, New York, NY 10010, USA. russell.thomson@nyumc.org

Trypanosome lytic factors (TLFs) are high-density lipoproteins and components of primate innate immunity. TLFs are characterized by their ability to kill extracellular protozoon parasites of the genus Trypanosoma. Two subspecies of Trypanosoma brucei have evolved resistance to TLFs and can consequently infect humans, resulting in the disease African sleeping sickness. The unique protein components of TLFs are a hemoglobin-binding protein, haptoglobin-related protein and a pore-forming protein, apoL-I. The recent advances in our understanding of the roles that these proteins play in the mechanism of TLF-mediated lysis are highlighted in this article. In light of recent data, which demonstrate that TLFs can ameliorate infection by the intracellular pathogen Leishmania, we also discuss the broader function of TLFs as components of innate immunity.

PMID: 19722834 [PubMed - in process]

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