Saturday, April 21, 2012

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 13

1. J Clin Microbiol. 2012 Apr 18. [Epub ahead of print]

A novel approach to in vitro drug susceptibility assessment of clinical strains of Leishmania spp.

Fernández O, Diaz-Toro Y, Valderrama L, Ovalle C, Valderrama M, Castillo H, Perez M, Saravia NG.

Source

Centro Internacional de Entrenamiento e Investigaciones Médica, Cali, Colombia.

Abstract

Resistance to antimonial drugs has been documented in Leishmania transmitted in South America, Europe and Asia. The frequency and distribution of resistance to these and other antileishmanial drugs is unknown. Technical constraints have limited the assessment of drug susceptibility of clinical strains of Leishmania. Susceptibility of experimentally selected lines and one-hundred-thirty clinical strains of L. panamensis, L. braziliensis and L. guyanensis to meglumine antimoniate and miltefosine was determined based on parasite burden and percentage of infected U-937 human macrophages. Reductions of infection at single predefined concentrations of meglumine antimoniate and miltefosine and ED(50) were measured and correlated. The effect of 34°C and 37°C incubation temperature and parasite to host cell ratios on drug susceptibility was evaluated at 5, 10 and 20 parasites/cell. Reduction of intracellular burden of Leishmania amastigotes in U-937 cells exposed to the predefined concentrations of meglumine antimoniate or miltefosine discriminated sensitive and experimentally derived resistant Leishmania populations, and was significantly correlated with ED(50) values of clinical strains (meglumine antimoniate: ρ = -0.926; P< 0.001; miltefosine: ρ = -0.906; P< 0.001). Incubation at 37°C significantly inhibited parasite growth compared to 34°C in the absence of antileishmanial drugs and resulted in a significantly lower ED(50) in the presence of drugs. Susceptibility assessment was not altered by parasite to cell ratio over the range evaluated. In conclusion, reduction of parasite burden at a single pre-determined drug concentration under standardized conditions provides an efficient and reliable strategy for susceptibility evaluation and monitoring of clinical strains of Leishmania.

PMID: 22518860 [PubMed - as supplied by publisher]
2. J Parasitol Res. 2012;2012:981686. Epub 2012 Feb 2.

Subversion of Immunity by Leishmania amazonensis Parasites: Possible Role of Phosphatidylserine as a Main Regulator.

Mendes Wanderley JL, Costa JF, Borges VM, Barcinski M.

Source

Universidade Federal do Rio de Janeiro, Pólo Universitário Macaé, Brazil.

Abstract

Leishmania amazonensis parasites cause progressive disease in most inbred mouse strains and are associated with the development of diffuse cutaneous leishmaniasis in humans. The poor activation of an effective cellular response is correlated with the ability of these parasites to infect mononuclear phagocytic cells without triggering their activation or actively suppressing innate responses of these cells. Here we discuss the possible role of phosphatidylserine exposure by these parasites as a main regulator of the mechanism underlying subversion of the immune system at different steps during the infection.

PMID: 22518276 [PubMed - in process]
3. J Trop Med. 2012;2012:254361. Epub 2012 Feb 7.

Information system and geographic information system tools in the data analyses of the control program for visceral leishmaniases from 2006 to 2010 in the sanitary district of venda nova, belo horizonte, minas gerais, Brazil.

Saraiva L, Leite CG, de Carvalho LO, Andrade Filho JD, de Menezes FC, Fiúza Vde O.

Source

Centro de Referência Nacional e Internacional para Flebotomíneos, Centro de Pesquisas René Rachou, 30190-002 Belo Horizonte, MG, Brazil.

Abstract

The aim of this paper is to report a brief history of control actions for Visceral Leishmaniasis (VL) from 2006 to 2010 in the Sanitary District (DS) of Venda Nova, Belo Horizonte, Minas Gerais, Brazil, focusing on the use of information systems and Geographic Information System (GIS) tools. The analyses showed that the use of an automated database allied with geoprocessing tools may favor control measures of VL, especially with regard to the evaluation of control actions carried out. Descriptive analyses of control measures allowed to evaluating that the information system and GIS tools promoted greater efficiency in making decisions and planning activities. These analyses also pointed to the necessity of new approaches to the control of VL in large urban centers.

PMID: 22518168 [PubMed - in process]
4. Clin Vaccine Immunol. 2012 Apr 18. [Epub ahead of print]

Identification and Diagnostic Utility of Leishmania infantum Proteins Found in Urine of Patients with Visceral Leishmaniasis.

Abeijon C, Kashino SS, Silva FO, Costa DL, Fujiwara RT, Costa CH, Campos-Neto A.

Source

DetectoGen Inc., Grafton, MA.

Abstract

Despite the clear need to control visceral leishmaniasis (VL), the existing diagnostic tests have serious shortcomings. Here, we introduce an innovative approach to directly identify Leishmania infantum antigens produced in vivo in humans with VL. We combined RP-HPLC with mass spectrometry and categorized three distinct L. infantum proteins presumably produced in bone marrow/spleen/liver and excreted in the urine of patients with VL. The genes coding for these proteins (L. infantum iron superoxide dismutase, NCBI accession: XP_001467866.1; L. infantum tryparedoxin, NCBI accession: XP_001466642.1; and L. infantum nuclear transport factor 2, NCBI accession XP_001463738.1) were cloned and the recombinant molecules were produced in E. coli. Antibodies to these proteins were produced in rabbits and chickens and were used to develop a capture ELISA designed to detect these L. infantum antigens in the urine of VL patients. Specificity of the antibodies was confirmed by Western blot analysis using both recombinant proteins and whole parasite extract. Importantly, a urinary antigen detection assay assembled with pairs of antibodies specific for each of these antigens identified 17 of 19 patients with VL. These results indicate that an improved antigen detection assay based on L. infantum proteins present in the urine of patients with VL may represent an important new strategy for the development of a specific and accurate diagnostic test that has the potential to both distinguish active VL from asymptomatic infection as well as to serve as an important tool to monitor therapy efficacy.

PMID: 22518013 [PubMed - as supplied by publisher]
5. J Infect Dis. 2012 Apr 18. [Epub ahead of print]

Leishmania-Induced Biphasic Ceramide Generation in Macrophages Is Crucial for Uptake and Survival of the Parasite.

Majumder S, Dey R, Bhattacharjee S, Rub A, Gupta G, Bhattacharyya Majumdar S, Saha B, Majumdar S.

Source

Division of Molecular Medicine, Bose Institute.

Abstract

The initial macrophage-Leishmania donovani interaction results in the formation of membrane platforms, termed lipid rafts, that help in the entry of the parasite. Therefore, it is imperative that the parasite designs a strategy to modulate its uptake and survival within the macrophages. Herein, we report Leishmania-triggered biphasic ceramide generation. In the first phase, L. donovani promastigotes induce activation of acid sphingomyelinase (ASMase), which catalyzes the formation of ceramide from sphingomyelin. Inhibition of ASMase resulted in reduced uptake and infection with the parasite. In the second phase, de novo synthesis generates ceramide that reduces the cellular cholesterol level and displaces the cholesterol from the membrane, leading to enhanced membrane fluidity, disruption of rafts, and impaired antigen-presentation to the T cells. The results reveal a novel role for ceramide in the perspective of L. donovani infection and help formulate an antileishmanial strategy that can possibly be applied to other intracellular infections as well.

PMID: 22517914 [PubMed - as supplied by publisher]
6. Planta Med. 2012 Apr 19. [Epub ahead of print]

Dihydrochalcones and Benzoic Acid Derivatives from Piper dennisii.

Cabanillas BJ, Le Lamer AC, Castillo D, Arevalo J, Estevez Y, Rojas R, Valadeau C, Bourdy G, Sauvain M, Fabre N.

Source

Université de Toulouse, UPS, UMR 152 (Pharmacochimie et Pharmacologie pour le Développement-PHARMA DEV), Toulouse, France.

Abstract

Two new dihydrochalcones (1, 2), as well as eight known compounds, piperaduncin C (3), 2',6'-dihydroxy-4'-methoxydihydrochalcone (4), 4,2',6'-trihydroxy-4'-methoxydihydrochalcone (5), 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoic acid (6), 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoic acid (7), 4-hydroxy-3-(3-methyl-2-butenoyl)-5-(3-methyl-2-butenyl)-benzoic acid (8), 2,2-dimethyl-8-(3-methyl-2-butenyl)-2H-1-chromene-6-carboxylic acid (9), and 3-(3',7'-dimethyl-2',6'-octadienyl)-4-methoxybenzoic acid (10) were isolated from the leaves of Piper dennisii Trelease (Piperaceae), using a bioassay-guided fractionation to determine their antileishmanial potential. Among them, compound 10 exhibited the best antileishmanial activity (IC50 = 20.8 µM) against axenic amastigote forms of Leishmania amazonensis, with low cytotoxicity on murine macrophages. In the intracellular macrophage-infected model, compound 10 proved to be more active (IC50 = 4.2 µM). The chemical structures of compounds 1-10 were established based on the analysis of the spectroscopic data.

Georg Thieme Verlag KG Stuttgart · New York.

PMID: 22516933 [PubMed - as supplied by publisher]
7. J Microbiol Immunol Infect. 2012 Apr 17. [Epub ahead of print]

Autoimmune manifestations in patients with visceral leishmaniasis.

Liberopoulos E, Kei A, Apostolou F, Elisaf M.

Source

Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece.

Abstract

Visceral leishmaniasis (VL) is a vector-borne protozoal infection caused by replication of Leishmania species in macrophages. VL is characterized by fever, hepatosplenomegaly and cytopenia. Apart from those classic clinical characteristics, VL has been associated with autoimmune clinical and laboratory features. Reported herein are 16 consecutive patients with VL who were checked for laboratory autoimmune manifestations. A variety of autoimmune antibodies including elevated titers of antinuclear antibodies and rheumatoid factor were detected in all patients. Of note, no laboratory autoimmune manifestations were detected in the seven patients who were re-evaluated 3 months after therapy. It is concluded that autoimmune laboratory manifestations during VL infection are common. These may mistakenly lead to diagnosis of an autoimmune disorder.

Copyright © 2012. Published by Elsevier B.V.

PMID: 22516744 [PubMed - as supplied by publisher]
8. Infect Genet Evol. 2012 Apr 10. [Epub ahead of print]

Evolution of the Leishmania braziliensis species complex from amplified fragment length polymorphisms, and clinical implications.

Odiwuor S, Veland N, Maes I, Arévalo J, Dujardin JC, Van der Auwera G.

Source

Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Center for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.

Abstract

In order to get more insight into its evolution and geographical distribution, we investigated the Leishmania (Viannia) braziliensis species complex using amplified fragment length polymorphisms and sequencing of a heat-shock protein 70 gene fragment. Previously, several assays had alluded to the high genetic diversity of the group, and single-locus assays typically identified two species, i.e. L. braziliensis and Leishmania peruviana, with occasional genetic signatures of both in the same strain. By analysis of 53 parasite isolates from Peru, and eight additional ones from other countries, we identified an atypical L. braziliensis cluster, and confirmed the origin of L. peruviana from the L. braziliensis cluster during the colonization of the western Andean coastal valleys. We discuss the clinical and taxonomical implications of our findings in relation to currently used species typing assays.

Copyright © 2012. Published by Elsevier B.V.

PMID: 22516226 [PubMed - as supplied by publisher]
9. Pathol Biol (Paris). 2012 Apr 17. [Epub ahead of print]

[Visceral leishmaniasis in immunocompetent adults. About six cases.]

[Article in French]
Essabbah Aguir N, Toumi A, Loussaïf C, Gorcii M, M'rad S, Ben Brahim H, Chakroun M, Babba H.

Source

Laboratoire de parasitologie-mycologie, hôpital Fattouma-Bourguiba, rue 1er-Juin, 5000 Monastir, Tunisie; Unité de recherche de parasitologie-mycologie, code 99-UR/08-05, faculté de pharmacie, université de Monastir, 1, rue Avicenne, 5000 Monastir, Tunisie.

Abstract

OBJECTIVE:

Studying the epidemiological variations of visceral leishmaniasis in Tunisia and proving the importance of parasitological investigations to raise the diagnosis.

PATIENTS AND METHODS:

Six patients hospitalised during the period between January 1998 and January 2009 at Fattouma Bourguiba Teaching Hospital in Monastir, five men and an only one woman, aged from 26 to 70 years old, originating from the central and eastern regions of the country. Epidemiological, clinical, biological and therapeutic data were obtained from the patient's medical files.

RESULTS:

The major clinical symptoms were fever, weakness and spleen enlargement. Biological data revealed the presence of anaemia in every case and leucopoenia associated or not associated with thrombopenia in four cases. The diagnosis of visceral leishmaniasis was confirmed by the identification of the parasite in the blood or in the bone marrow. All patients were treated with two courses of antimoniate of meglumine separated by a 6-week interval. The outcome was positive and the patients were cured.

CONCLUSION:

Visceral leishmaniasis is increasing among adults in Tunisia. Moreover, it is spreading outside its epidemiological area in the north to reach the central and southern regions. It should be raised when fever and spleen enlargement occur. Biological data are hardly specific. Diagnosis is based on finding the parasite in human fluids, mainly by molecular techniques. The rapid establishment of a specific treatment is vital.

Copyright © 2012. Published by Elsevier SAS.

PMID: 22516103 [PubMed - as supplied by publisher]
10. J Control Release. 2012 Apr 10. [Epub ahead of print]

The efficacy of aerosol treatment with non-ionic surfactant vesicles containing amphotericin B in rodent models of leishmaniasis and pulmonary aspergillosis infection.

Alsaadi M, Italia JL, Mullen AB, Kumar MN, Candlish AA, Williams RA, Shaw C, Al Gawhari F, Coombs GH, Wiese M, Thomson AH, Puig-Sellant M, Wallace J, Sharp A, Wheeler L, Warn P, Carter KC.

Source

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK.

Abstract

Amphotericin B (AMB) is used to treat both fungal and leishmanial infections, which are of major significance to human health. Clinical use of free AMB is limited by its nephrotoxicity, whereas liposomal AMB is costly and requires parental administration, thus development of novel formulations with enhanced efficacy, minimal toxicity and that can be applied via non-invasive routes is required. In this study we analysed the potential of non-ionic surfactant vesicles (NIV) given by nebulisation to deliver AMB to the lungs, liver and skin. Treatment with AMB-NIV resulted in significantly higher drug levels in the lungs and skin (p<0.05) compared to similar treatment with AMB solution but significantly lower plasma levels (p<0.05). Treatment with AMB-NIV resulted in a significant reduction in fungal lung burdens in a rat model of invasive pulmonary aspergillosis (p<0.05) compared to treatment with the carrier alone. Treatment with AMB-NIV but not AMB solution significantly suppressed Leishmania donovani liver parasite burdens (p<0.05) but could not inhibit the growth of cutaneous Leishmania major lesions. The results of this study indicate that aerosolised NIV enhanced pulmonary and hepatic delivery whilst minimising systemic exposure and toxicity.

Copyright © 2012. Published by Elsevier B.V.

PMID: 22516093 [PubMed - as supplied by publisher]

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