Wednesday, September 23, 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 -9 of 9

1: Am J Dermatopathol. 2009 Sep 18. [Epub ahead of print]

Factor XIIIa+ Dermal Dendrocyte Parasitism in American Tegumentary Leishmaniasis Skin Lesions.

Sotto MN, Halpern I, Kauffman MR, Pagliari C.

From the *Departments of Dermatology; and daggerPathology, University of São Paulo Medical School, São Paulo, Brazil.

Dendritic cells belong to a family of antigen-presenting cells that are localized at the entry sites, such as skin and mucosa. Dendritic cells are related to immune surveillance function. The role of Langerhans cells in the pathogenesis of skin infectious diseases is well studied; however, there are few articles addressing involvement of factor XIIIa-positive dermal dendrocytes (FXIIIa+ DD) in such processes. FXIIIa+ DDs are bone marrow-monocytic lineage-derived cells and members of the skin immune system. Due to their immune phenotype and functional characteristics, they are considered complementary cells to Langerhans cells in the process of antigen presentation and inducing immune response. To verify the interaction between FXIIIa+ DD and Leishmania amastigotes, 22 biopsies of American tegumentary leishmaniasis (ATL) skin lesions were subjected to double staining technique with anti-factor XIIIa and anti-Leishmania antibodies. FXIIIa+ DDs were hypertrophic and abundant in the cutaneous reaction of ATL. FXIIIa+ DDs harboring parasites were observed in 11 of 22 skin biopsies. The data obtained suggest that FXIIIa+ DD plays a role in the pathogenesis of ATL skin lesion as host cell, immune effector, and/or antigen-presenting cell.

PMID: 19770631 [PubMed - as supplied by publisher]

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2: Arch Dermatol. 2009 Sep;145(9):1023-6.

Leishmania tropica-induced cutaneous and presumptive concomitant viscerotropic leishmaniasis with prolonged incubation.

Weiss F, Vogenthaler N, Franco-Paredes C, Parker SR.

Department of Dermatology, Grady Memorial Hospital, Emory University, 1365 Clifton Rd NE, Ste 1100, Bldg A, Atlanta, GA 30322, USA.

BACKGROUND: Leishmaniasis includes a spectrum of diseases caused by protozoan parasites belonging to the genus Leishmania. The disease is traditionally classified into visceral, cutaneous, or mucocutaneous leishmaniasis, depending on clinical characteristics as well as the species involved. Leishmania tropica is one of the causative agents of cutaneous leishmaniasis, with a typical incubation period of weeks to months. Observation We describe a 17-year-old Afghani girl who had lived in the United States for 4 years and who presented with a 6-month history of pretibial ulcerations, 9.1-kg weight loss, abdominal pain, splenomegaly, and extreme fatigue. Histopathologic examination and culture with isoenzyme electrophoresis speciation of her skin lesions confirmed the presence of L tropica. In addition, results of serum laboratory and serological studies were highly suggestive of concomitant visceral involvement. The patient was treated with a 28-day course of intravenous pentavalent antimonial compound sodium stibogluconate with complete resolution of her systemic signs and symptoms and improvement of her pretibial ulcerations. CONCLUSIONS: This is an exceptional case in that our patient presented with disease after an incubation period of years rather than the more typical weeks to months. In addition, this patient had confirmed cutaneous involvement, as well as strong evidence of viscerotropic disease caused by L tropica, a species that characteristically displays dermotropism, not viscerotropism.

PMID: 19770442 [PubMed - in process]

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3: Antimicrob Agents Chemother. 2009 Sep 21. [Epub ahead of print]

The antituberculosis drug pyrazinamide affects the course of cutaneous leishmaniasis in vivo and increases macrophage and dendritic cell activation.

Mendez S, Traslavina R, Hinchman M, Huang L, Green P, Cynamon MH, Welch JT.

Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca NY 14853; Department of Medicine, Veterans Affairs Medical Center, Syracuse, NY 13210; Department of Chemistry, University at Albany-SUNY, Albany, NY 12222.

Antileishmanial therapy is suboptimal due to toxicity, high cost, and development of resistance to available drugs. Pyrazinamide (PZA) is a constituent of short-course tuberculosis chemotherapy. We investigated the effect of PZA on Leishmania major promastigotes and amastigote survival. Promastigotes were more sensitive to the drug than amastigotes, with MIC50 of 16.1 and 8.2 microM respectively (48 hours post treatment). Moreover, 90% amastigotes were eliminated at 120 hours post treatment, indicating that longer treatments will result in parasite elimination. Most strikingly, PZA treatment of infected C57BL/6 mice resulted in protection against disease and in a 100-fold reduction in parasite burden. PZA treatment of J774 cells and bone marrow-derived dendritic cells and macrophages, increased IL-12, TNF-alpha and activation marker expression, as well as nitric oxide production, suggesting that PZA enhances effective immune responses against the parasite. PZA also treatment activates dendritic cells deficient in Toll-like Receptor-2 and -4 expression to initiate a proinflammatory response, confirming that the immunostimulatory effect of PZA is directly caused by the drug and independent of Toll-like receptor stimulation. These results are not only strongly indicative of the promise of PZA as alternative anti-leishmanial chemotherapy, but they also suggest that PZA causes collateral immunostimulation, a phenomenon that has never been reported for this drug.

PMID: 19770283 [PubMed - as supplied by publisher]

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Patient Drug Information

  • Pyrazinamide

    Pyrazinamide kills or stops the growth of certain bacteria that cause tuberculosis (TB). It is used with other drugs to treat tuberculosis.

  • Source: AHFS Consumer Medication Information
4: J Theor Biol. 2009 Sep 18. [Epub ahead of print]

Transmission dynamics and underreporting of Kala-Azar in the Indian state of Bihar.

Mubayi A, Castillo-Chavez C, Chowell G, Kribs-Zaleta C, Ali Siddiqui N, Kumar N, Das P.

Mathematical & Computational Modeling Sciences Center, Arizona State University, AZ, USA; School of Human Evolution and Social Change, Arizona State University, AZ, USA; Department of Mathematics, The University of Texas at Arlington, TX, USA; Prevention Research Center, Berkeley, CA, USA.

"Kala-azar" (or Indian Visceral Leishmaniasis) is a vector-borne infectious disease affecting communities in tropical and subtropical areas of the world. Bihar, a state in India, has one of the highest prevalence and mortality reported levels of Kala-azar. Yet, the magnitude of the problem is difficult to assess because most cases are handled by private health providers who are not required to and do not report them to the Ministry of Health. The impact of underreporting using district-level reported incidence data from the state of Bihar is the main goal of this manuscript. We derive expressions for, and compute estimates of Kala-azar's reproduction numbers, an indirect measure of disease prevalence, and levels of underreporting for the 21 districts of Bihar. The average reproduction number (number of secondary cases generated per infective) estimates for Bihar range from 1.3 (2003) to 2.1 (2005) with some districts' estimates with mean values lower than one. Model estimates (using available data and a model-derived expression) show that the proportion of underreported cases declined from an average of 88% in 2003 to 73% in 2005. However, 8 districts in 2003 and 5 districts in 2005 had more than 90% levels of underreporting. Model estimates are used to generate underreporting adjusted incidence rates. The analysis finds that reported data misidentify four of the eight (2003) and three of the nine (2005) districts classified as high-risk. In fact, seven (2003) and five (2005) of the most affected Kala-azar districts had been classified as low-risk when only reported incidence data were used.

PMID: 19769990 [PubMed - as supplied by publisher]

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5: Exp Parasitol. 2009 Sep 18. [Epub ahead of print]

Leishmania major lipophosphoglycan: Discrepancy in toll-like receptor signaling.

Kavoosi G, Ardestani SK, Kariminia A, Alimohammadian MH.

Institute of Biotechnology, University of Shiraz, Shiraz, Iran.

Lipophosphoglycan (LPG) is structurally characterized by a series of phosphoglycan repeat units. Cellular LPG, isolated from promastigotes, has a very similar structure to culture supernatant LPG, but differs in the average number of phosphorylated oligosaccharide repeat units and in glycan composition. Comparison of these LPGs with capillary electrophoresis and immunoblotting indicate that these molecules are highly conserved structurally and composed of galactosylated Gal-Man repeats but their size and molecular weight are very different which is due to glycan portion. There are 30 and 20 repeat units in sLPG and mLPG respectively. Both LPGs induced nitric oxide in macrophages cell line while sLPG had the higher stimulatory effect. In the presence of anti-TLR2 nitric oxide stimulated by LPG was reduced to control levels. In addition, in the presence of anti-TLR4, nitric oxide stimulated by LPGs was not affected. We propose that lipophosphoglycan induces nitric oxide production via TLR2 signaling pathway.

PMID: 19769970 [PubMed - as supplied by publisher]

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6: Acta Trop. 2009 Sep 18. [Epub ahead of print]

PCR for Diagnosis and Assessment of Cure in Kala-azar Patients in Bangladesh.

Salam MA, Mondal D, Kabir M, Ekram AR, Haque R.

Department of Microbiology, Rajshahi Medical College, Rajshahi, Bangladesh.

The study evaluated the usefulness of Leishmania nested polymerase chain reaction (Ln-PCR) for diagnosis of kala-azar and assessed its role as a test of cure among kala-azar patients in Bangladesh. Peripheral blood buffy coat Ln-PCR was done in ninety seven (97) clinically-suspected patients of kala-azar, in forty (40) healthy controls from both endemic and non-endemic areas, and in 46 patients after completion of treatment with sodium stibogluconate (SSG). The Ln-PCR results were compared with Leishmania donovani parasite load graded by 1+ to 6+ in all smear-positive Leishmania donovani cases. Out of 97 clinically-suspected kala-azar pateints, 94 were parasitologically confirmed. Ln-PCR was found positive in 91 of 94 parasitologically-positive patients of kala-azar at diagnosis, indicating its diagnostic sensitivity as 97%. None of the controls was found positive for Ln-PCR, indicating its diagnostic specificity to be 100%. About 9% of kala-azar patients having been graded 1+ parasitic load had negative Ln-PCR results. After completion of treatment, Ln-PCR was positive in 4 patients (8.4%) out of 46 cases, indicating its role in demonstrating the absence of parasites 30 days after completion of treatment in 91.6% of the treated patients. This limited study suggests that Ln-PCR is a highly sensitive and specific test for the diagnosis of visceral leishmaniasis and can be used as a test of cure. Thus, efforts should be made to establish this useful method at least in the tertiary care hospitals and, if possible, at the district-level hospitals, especially in the endemic areas of Bangladesh.

PMID: 19769932 [PubMed - as supplied by publisher]

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7: Biochem J. 2009 Sep 22. [Epub ahead of print]

Leishmania donovani RAN-GTPase interacts at the nuclear rim with linker histone H1.

Smirlis D, Boleti H, Gaitanou M, Soto M, Soteriadou K.

Ran-GTPase regulates multiple cellular processes such as nucleo-cytoplasmic transport, mitotic spindle assembly, nuclear envelope assembly, cell-cycle progression and the mitotic checkpoint. The leishmanial Ran protein contrary to its mammalian counterpart which is predominately nucleoplasmic is localised at the nuclear rim. The focus of this paper was to characterise the L.donovani Ran orthologue (LdRan) with emphasis on the Ran-histone association. LdRan was found to be developmentally regulated, expressed three times less in the amastigote stage. LdRan over-expression caused a growth defect linked to a delayed S-phase progression in promastigotes like its mammalian counterpart. We report for the first time that Ran interacts with a linker histone -histone H1- in vitro and that the two proteins co-localise at the parasite nuclear rim. Interaction of Ran with core histones H3 and H4, creating in metazoans a chromosomal Ran-GTP gradient important for mitotic spindle assembly, is speculative in Leishmania spp., not only because this parasite undergoes a closed mitosis but also because the main localisation of LdRan is different from that of core histone H3. Interaction of Ran with the leishmanial linker histone H1 (LeishH1), suggests that this association maybe involved in modulation of other pathways than those documented for the metazoan Ran-core histone association.

PMID: 19769568 [PubMed - as supplied by publisher]

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8: J Med Entomol. 2009 Sep;46(5):1159-63.

Natural infection of Lutzomyia neivai and Lutzomyia sallesi (Diptera: Psychodidae) by Leishmania infantum chagasi in Brazil.

Saraiva L, Carvalho GM, Gontijo CM, Quaresma PF, Lima AC, Falcão AL, Andrade Filho JD.

Laboratório de Leishmanioses, Instituto René Rachou-Fiocruz, Av. Augusto de Lima 1715, CEP 30190-002 Belo Horizonte, MG, Brazil.

Natural infections with Leishmania were found in females of the phlebotomine sand flies Lutzomyia neivai (Pinto) (= Nyssomyia neivai) and Lutzomyia sallesi (Galvão & Coutinho) (= Evandromyia sallesi) (Diptera: Psychodidae) from Lassance, in the Brazilian state of Minas Gerais. Promastigotes were found in the pyloric region of the former species and in the abdominal midgut of the latter species. Insects found to be infected by microscopic examination were macerated in saline solution and inoculated into hamsters. Subsequent analysis by polymerase chain reaction-restriction fragment length polymorphism revealed both isolates to belong to the species Leishmania infantum chagasi Cunha & Chagas.

PMID: 19769049 [PubMed - in process]

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9: J Med Entomol. 2009 Sep;46(5):1094-8.

Phlebotomus perfiliewi transcaucasicus, a vector of Leishmania infantum in northwestern Iran.

Rassi Y, Javadian E, Nadim A, Rafizadeh S, Zahraii A, Azizi K, Mohebali M.

Department of Medical Entomology and Vector Control, School of Public Health, Tehran University of Medical Sciences, P.O. Box 6446-14155, Tehran, Iran. rassiy@sina.tums.ac.ir

Visceral leishmaniasis is caused by Leishmania infantum, which is transmitted to humans by bites of phlebotomine sand flies and is one of the most important public health problems in Iran. To identify the vector(s), an investigation was carried out in Germi district, an important focus of the disease in Ardebil province in northwestern Iran, during July-September 2004 and 2005. Using sticky papers, CDC light traps and aspirators, 3,560 sand flies were collected and identified to species. Host bloodmeal preference and Leishmania infections in female specimens were evaluated using enzyme-linked immunosorbent assay (ELISA) for the former and microscopic examination followed by polymerase chain reaction (PCR) assay using species-specific kinetoplast minicircle primers for the latter. Nine sand fly species are present in the district, including Phlebotomus kandelakii Shchurenkova, Phlebotomus perfiliewi transcaucasicus Perfil'ev, Phlebotomus major Annandale, Phlebotomus balcanicus Theodor, Phlebotomus halepensis Theodor, Phlebotomus brevis Theodor & Meshghali, Phlebotomus papatasi Scopoli, Sergentomyia dentata Sinton, and Sergentomyia sintoni Pringle, with P. p. transcaucasicus being the most prevalent representative of the genus Phlebotomus at 45%. The anthropophilic index for P. p. transcaucasicus was 36.3%, indicating a strong preference for humans. Of 905 female P. p. transcuacasicus dissected, 10 (1.1%) were found naturally infected with promastigotes. Species-specific amplification of promastigotes eluted from Giemsa-stained slides revealed specific PCR products of L. infantum DNA. Based on its high anthropophily and natural infections with L. infantum, and the fact that it was the only species found infected with L. infantum, we conclude that P. p. transcaucasicus is the principal vector of L. infantum in northwestern Iran.

PMID: 19769040 [PubMed - in process]

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