Wednesday, September 16, 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 -7 of 7

1: Interdiscip Perspect Infect Dis. 2009;2009:802712. Epub 2009 Jun 4.

New means of canine leishmaniasis transmission in north america: the possibility of transmission to humans still unknown.

Petersen CA.

2764 Veterinary Medicine, Department of Veterinary Pathology, Iowa State University, Ames, IA 50011, USA.

At present it is not possible to determine in advance the outcome of Leishmania infantum infection. Canine Visceral Leishmaniasis (VL), caused by Le. infantum, is a natural disease process which offers a insight into the interaction of the host and resultant disease outcome. Canine VL results in the same altered pathophysiology and immunodysregulation seen in humans. VL in US dogs is likely to be transmitted primarily via nontraditional, nonvector means. VL mediated by Le. infantum is endemic in U.S. Foxhound dogs, with vertical transmission likely to be the novel primary means of transmission. This population of dogs offers an opportunity to identify host factors of natural disease. Prevention of human clinical visceral leishmaniasis can occur only by better understanding the disease ecology of the primary reservoir host: the dog.

PMID: 19753139 [PubMed - in process]

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2: Antimicrob Agents Chemother. 2009 Sep 14. [Epub ahead of print]

In vitro sensitivity testing of Leishmania clinical field isolates: pre-conditioning of promastigotes enhances infectivity for macrophage host cells.

Inocêncio da Luz R, Vermeersch M, Dujardin JC, Cos P, Maes L.

Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium; Laboratory of Molecular Parasitology, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium.

Diagnostic material from patients with leishmaniasis is generally available as promastigotes and proper susceptibility testing to first-line drugs using the intracellular amastigote assay is frequently hampered by poor infectivity for the macrophage host cell. Several conditions were investigated to optimize the in vitro metacyclogenesis and cell-infectivity of L. donovani, L. guyanensis and L. braziliensis field strains obtained from patients receiving standard antimony medication. Triggering log-phase promastigotes to become 'amastigote-like' by increasing temperature or acidifying the culture medium was not successful. Adequate metacyclogenesis and highest levels of macrophage infection were obtained after pre-conditioning 5-day-old late log-phase promastigote cultures at 25 degrees C to pH 5.4 for 24h in Schneider's medium prior to infection. The susceptibility assay on primary peritoneal mouse macrophages included pentavalent antimony (Sb(V): sodium-stibogluconate), trivalent antimony (Sb(III): potassium antimonyl tartrate), miltefosine and the experimental drug PX-6518. All strains were sensitive to miltefosine (IC50 <10microM) and PX-6518 (IC50 <2microg/ml), but showed a distinct susceptibility to either Sb(V) and/or Sb(III) depending whether they were derived from 'cured', 'relapse' or 'non-responder' patients. Within the available set of Leishmania species and strains, simultaneous Sb(V)-Sb(III) resistance was clearly associated with treatment failure, however, a larger set of isolates is still needed to judge the predictive value of Sb(V)-Sb(III) susceptibility profiling on treatment outcome. In conclusion, the proposed conditioning protocol further contributes towards a more standardized laboratory model for drug sensitivity evaluation of field isolates.

PMID: 19752271 [PubMed - as supplied by publisher]

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3: Dev Biol. 2009 Sep 11. [Epub ahead of print]

Characterization of the Caenorhabditis elegans UDP-Galactopyranose mutase homolog glf-1 reveals an essential role for galactofuranose metabolism in nematode surface coat synthesis.

Novelli JF, Chaudhary K, Canovas J, Benner J, Medinger C, Kelly P, Hodgkin J, Carlow CK.

New England Biolabs, Inc., Division of Molecular Parasitology, 240 County Road, Ipswich, MA 01938, USA.

Galactofuranose (Gal(f)), the furanoic form of D-galactose produced by UDP-Galactopyranose mutases (UGMs), is present in surface glycans of some prokaryotes and lower eukaryotes. Absence of the Gal(f) biosynthetic pathway in vertebrates and its importance in several pathogens make UGMs attractive drug targets. Since the existence of Gal(f) in nematodes has not been established, we investigated the role of the Caenorhabditis elegans UGM homolog glf-1 in worm development. glf-1 mutants display significant late embryonic and larval lethality, and other phenotypes indicative of defective surface coat synthesis, the glycan-rich outermost layer of the nematode cuticle. The glf homolog from the protozoan Leishmania major partially complements C. elegans glf-1. glf-1 mutants rescued by L. major glf, which behave as glf-1 hypomorphs, display resistance to infection by Microbacterium nematophilum, a pathogen of rhabditid nematodes thought to bind to surface coat glycans. To confirm the presence of Gal(f) in C. elegans, we analyzed C. elegans nucleotide sugar pools using online Electrospray Ionization Mass Spectrometry (ESI-MS). UDP-Gal(f) was detected in wild-type animals while absent in glf-1 deletion mutants. Our data indicate that Gal(f) likely has a pivotal role in maintenance of surface integrity in nematodes, supporting investigation of UGM as a drug target in parasitic species.

PMID: 19751718 [PubMed - as supplied by publisher]

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4: Parasite Immunol. 2009 Oct;31(10):646-51.

Foxp3 expression in lesions of the different clinical forms of American tegumentary leishmaniasis.

Carneiro FP, DE Magalhães AV, DE Jesus Abreu Almeida Couto M, Bocca AL, Muniz-Junqueira MI, Ribeiro Sampaio RN.

Department of Pathology, University of Brasília, Brasília, Brazil.

Summary As the diversity in clinical presentation of American tegumentary leishmaniasis (ATL) is determined mainly by the immune response of host, our aim was to evaluate the in situ expression of Foxp3 [marker of regulatory T (Treg) cell] in lesions of the different clinical forms of ATL. Foxp3(+) cells were observed in 39.5% (32/81) of the samples and the number of positive cells was low in all the clinical forms. Even presenting a significantly lower number of CD4(+) T cells, diffuse cutaneous leishmaniasis (DCL) showed a higher expression of Foxp3 when compared with localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). In LCL and MCL, the number of Foxp3(+) cells correlated positively with the number of apoptotic cells (active caspase-3(+) cells). A positive correlation was also observed between the expression of active caspase-3 and FasL in these clinical forms. Our data suggest that increased number of Treg cells may be associated to the hyporesponsiveness observed in DCL and also indicate that the apoptosis may be a possible mechanism of action of Foxp3(+) Treg cell in LCL and MCL. However, further studies are required to better understand the mechanism of action of Treg cell.

PMID: 19751477 [PubMed - in process]

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5: Parasite Immunol. 2009 Oct;31(10):623-30.

Antileishmanial and immunomodulatory activity of Xylopia discreta.

López R, Cuca LE, Delgado G.

Grupo de Investigación en Inmunotoxicología, Departamento de Farmacia, Universidad Nacional de Colombia, Bogotá, Colombia.

Summary This study aimed at determining the in vitro antileishmanial activity of the essential oil and eight extracts obtained from Xylopia discreta. J774 and U937 macrophages were exposed to the different substances to establish the median lethal concentration (LC(50)). The median effective concentration (EC(50)) was obtained by determining the reduction of Leishmania panamensis-infected cells. A selectivity index (SI) (LC(50)/EC(50)) >/= 20 defined a specific activity for one Xylopia discreta leaf extracts and for the essential oil, being these the two that showed the highest activity (SI = 64.8 and 110, respectively in J774 cells). To assess the substances' immunomodulatory activity, pro- and anti-inflammatory soluble mediators produced after treating infected macrophages were quantified by flow cytometry. The leaf methanol extract and the essential oil induced a differential production of monocyte chemoattractant protein-1, a chemokine associated with a Leishmania-resistant phenotype (Th1).

PMID: 19751474 [PubMed - in process]

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6: Parasite Immunol. 2009 Oct;31(10):587-96.

Protein-energy malnutrition as a risk factor for visceral leishmaniasis: a review.

Malafaia G.

Laboratório de Imunoparasitologia, Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Instituto de Ciências Exatas e Biológicas (ICEB), Universidade Federal de Ouro Preto (UFOP), Ouro Preto - MG, Brazil.

Summary The protein-energy malnutrition (PEM) and visceral leishmaniasis (VL) are important problems of public health, which affect millions of people worldwide. Currently, it has been accepted that the immunity or susceptibility to infect-parasitic diseases are directly related to the nutritional status of the host. However, the mechanisms that govern the relationship between the PEM and the course of the VL are multiple and little explained. In this study the current most important aspects and the synergism between these two illnesses were presented. Bibliographic search includes empirical reports, reviews, commentaries, reports from professional associations, books, editorials and annals of congress published in diverse languages between 1960 and January 2009. As much the PEM as the infections caused by parasites of the Leishmania genus are frequent problems in the current days. As new studies are developed on the subject, it becomes essential that the society knows them.

PMID: 19751470 [PubMed - in process]

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7: Scand J Immunol. 2009 Oct;70(4):389-95.

Effects of Salivary Gland Homogenate from Wild-Caught and Laboratory-Reared Lutzomyia longipalpis on the Evolution and Immunomodulation of Leishmania (Leishmania) amazonensis Infection.

Laurenti MD, da Matta VL, Pernichelli T, Secundino NF, Pinto LC, Corbett CE, Pimenta PP.

Laboratory of Pathology of Infectious Diseases (LIM-50), Department of Pathology, Medical School, University of São Paulo, São Paulo (SP), Brazil.

We investigated the effects of Lutzomyia longipalpis salivary glands homogenate of wild-caught and laboratory-reared vectors on the lesion evolution and immunomodulation of the infection caused by Leishmania (Leishmania) amazonensis. To compare the effect of both salivary glands homogenate (SGH), C57BL/6 mice were inoculated subcutaneously into the hind footpads or into the ear dermis with 10(6) promastigotes in the presence or not of SGH from wild-caught and laboratory-colonized sand flies. Comparing SGH groups, the lesion size was lower in mice co-inoculated with wild-caught SGH, as the parasitism and the infiltration of macrophages at the inoculation site. Wild-caught SGH also determined lower production of IL-4 and IL-10 but higher IL-12 levels compared with laboratory-reared SGH. Our findings address a probable bias by using SGH from laboratory-colonized sand flies instead of wild-caught vector SGH in studies concerning saliva effects. A possible mild influence of sand fly saliva in natural infections caused by Leishmania is also speculated, as infection is transmitted by wild and not by laboratory-reared vectors.

PMID: 19751274 [PubMed - in process]

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