Tuesday, October 20, 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 14

1: Saudi Med J. 2009 Oct;30(10):1365.

Serodiagnosis of cutaneous leishmaniasis in the Syrian Arab Republic.

Al-Mendalawi MD, Al-Nahhas SA.

Department of Paediatrics, Al-Kindy College of Medicine, Baghdad University, Baghdad, Iraq.

PMID: 19838453 [PubMed - in process]

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2: Eur J Med Chem. 2009 Sep 18. [Epub ahead of print]

Anti-trypanosomatid benzofuroxans and deoxygenated analogues: Synthesis using polymer-supported triphenylphosphine, biological evaluation and mechanism of action studies.

Castro D, Boiani L, Benitez D, Hernández P, Merlino A, Gil C, Olea-Azar C, González M, Cerecetto H, Porcal W.

Departamento de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.

Hybrid vinylthio-, vinylsulfinyl-, vinylsulfonyl- and vinylketo-benzofuroxans developed as anti-trypanosomatid agents, against Trypanosoma cruzi and Leishmania spp., have showed low micromolar IC(50) values. The synthetic route to access to these derivatives was an efficient Wittig reaction performed in mild conditions with polymer-supported triphenylphosphine (PS-TPP). Additionally, the benzofurozan analogues, deoxygenated benzofuroxans, were prepared using PS-TPP as reductive reagent in excellent yields. The trypanosomicidal and leishmanocidal activities of the benzofuroxan derivatives were measured and also some aspects of their mechanism of action studied. In this sense, inhibition of mitochondrial dehydrogenases activities, production of intra-parasite free radicals and cruzipain inhibition were studied as biological target for the anti-trypanosomatid identified compounds. The trypanosomicidal activity could be the result of both the parasite-mitochondrion function interference and production of oxidative stress into the parasite.

PMID: 19837489 [PubMed - as supplied by publisher]

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3: Lancet. 2009 Oct 17;374(9698):1330.

Visceral leishmaniasis: time to better use existing resources.

Reithinger R, Brooker S, Kolaczinski JH.

London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK; George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

PMID: 19837253 [PubMed - in process]

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4: J Theor Biol. 2009 Oct 15. [Epub ahead of print]

Parameter estimation and sensitivity analysis in an agent-based model of Leishmania major infection.

Dancik GM, Jones DE, Dorman KS.

Program in Bioinformatics and Computational Biology, Rm 533 Science II, Iowa State University, Ames, IA 50011, USA.

Computer models of disease take a systems biology approach toward understanding host-pathogen interactions. In particular, data driven computer model calibration is the basis for inference of immunological and pathogen parameters, assessment of model validity, and comparison between alternative models of immune or pathogen behavior. In this paper we describe the calibration and analysis of an agent-based model of Leishmania major infection. A model of macrophage loss following uptake of necrotic tissue is proposed to explain macrophage depletion following peak infection. Using Gaussian processes to approximate the computer code, we perform a sensitivity analysis to identify important parameters and to characterize their influence on the simulated infection. The analysis indicates that increasing growth rate can favor or suppress pathogen loads, depending on the infection stage and the pathogen's ability to avoid detection. Subsequent calibration of the model against previously published biological observations suggests that L. major has a relatively slow growth rate and can replicate for an extended period of time before damaging the host cell.

PMID: 19837088 [PubMed - as supplied by publisher]

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5: Trans R Soc Trop Med Hyg. 2009 Oct 15. [Epub ahead of print]

Comment on: Cutaneous and mucocutaneous leishmaniasis in Tigray, northern Ethiopia: clinical aspects and therapeutic concerns.

Dorlo TP, Kager PA.

Center for Infection and Immunity Amsterdam, Division of Infectious Diseases, Tropical Medicine & AIDS, Academic Medical Center, Amsterdam, The Netherlands.

PMID: 19836815 [PubMed - as supplied by publisher]

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6: Arch Pediatr. 2009 Oct;16S2:S96-S100.

[Leishmaniases in France: an update.]

[Article in French]

Marty P, Pomares-Estran C, Hasseine L, Delaunay P, Haas H, Rosenthal E.

Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire l'Archet, BP 3079, 062002 Nice cedex 3.

Leishmaniases are parasitic diseases due to a flagellate protozoan of the genus Leishmania. They are transmitted from mammal to mammal by the bite of an arthropod vector : a female sandfly. Among the different clinical presentations, the zoonotic visceral leishmaniasis (ZVL) is due to Leishmania infantum. Dogs are the reservoir and can develop a deadly disease. ZVL is described in China, Pakistan, Latin America and in the Mediterranean region, particularly in the South of France. In recent years, many asymptomatic carriers have been described. Despite the fact that cases in immunocompromised adults are the majority, the classic Mediterranean ZVL in young children is still observed. The classic triad of symptoms is : fever, pallor, splenomegaly and hepatomegaly in half of the cases. The biological orientation is a low blood count (anemia, leuconeutropenia, and thrombocytopenia) and an inflammatory syndrome. Serological tests are useful, but the diagnosis is made by the identification of the parasite in a bone marrow sample. Today, the treatment is done by the liposomal amphotericin B (AmBisome((R))) and the total dose must to be 20mg/kg.

PMID: 19836685 [PubMed - as supplied by publisher]

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7: Arch Pediatr. 2009 Oct;16S2:S129-S131.

[Pseudotumoral-like recurrence of visceral leishmaniasis in a seven-year-old girl.]

[Article in French]

Jeziorski E, Blanchet C, Ludwig C, Lalande M, Coste V, Dereure J, Rodière M.

CHU de Montpellier, Hôpital Arnaud de Villeneuve, Service de Pédiatrie III, 371, avenue du Doyen Gaston Giraud, 34295 Montpellier cedex 5; Université Montpellier 1, CS 59001, Faculté de Médecine de Montpellier, 2 rue Ecole de médecine, 34060 Montpellier cedex 2.

Visceral leishmaniasis is endemic around Mediterranean and is considered by certain authors as an opportunist disease. We report on the case of a 7-year-old girl treated by anti-TNF for an idiopathic juvenile arthritis which has presented a visceral leishmaniasis. Four years later, she presented a pseudotumoral-like recurrence located in a nasal mucous membrane. Leishmania infantum is classically responsible for visceral leishmaniasis but pure mucocutaneous leismaniasis has been described. It is, for our knowledge, the first observation of a recurrence of visceral leishmaniasis in a mucocutaneous location. Atypical leishmaniasis in the endemic zones can appear in immunodepressed patients and must be evoked when in doubt.

PMID: 19836676 [PubMed - as supplied by publisher]

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8: Vet J. 2009 Oct 14. [Epub ahead of print]

Clinical and laboratory monitoring of dogs naturally infected by Leishmania infantum.

Paradies P, Sasanelli M, de Caprariis D, Testini G, Traversa D, Lia RP, Dantas-Torres F, Otranto D.

Department of Veterinary Public Health and Animal Sciences, Faculty of Veterinary Medicine of Bari, Str. Prov. per Casamassima km 3, 70010 Valenzano, Italy.

The clinical evolution of Leishmania infantum infection in dogs is largely influenced by the host's individual immune response. Few studies have investigated the time course and clinical evolution of the infection both under experimental and natural conditions. In the present investigation, the time course of L. infantum infection was studied by monitoring clinical and laboratory features in naturally infected dogs sheltered in southern Italy. Twenty-three dogs that had one or more positive diagnostic tests for L. infantum were enrolled in the study and followed up every 4months. A clinical score was assigned at each visit after assessing the presence of clinical signs suggestive of leishmaniosis. L. infantum-infected dogs were classified into three different categories based on their clinical score and serological and parasitological test results. Based on data from diagnostic tests and clinical scores, the time course of infection was defined as transient asymptomatic infection (11 dogs), persistent asymptomatic infection (2 dogs), and symptomatic infection (8 dogs). Two dogs were lost after the first sand fly season. The results of the present study provide a framework for assessing the clinical status of L. infantum infection in dogs and suggest that infected animals should be monitored over time to expedite therapeutic decisions and plan appropriate control interventions.

PMID: 19836279 [PubMed - as supplied by publisher]

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9: Parasitology. 2009 Oct 16:1-20. [Epub ahead of print]

Transmission, reservoir hosts and control of zoonotic visceral leishmaniasis.

Quinnell RJ, Courtenay O.

Institute of Integrative and Comparative Biology, University of Leeds, Leeds LS2 9JT, UK.

SUMMARYZoonotic visceral leishmaniasis (ZVL) caused by Leishmania infantum is an important disease of humans and dogs. Here we review aspects of the transmission and control of ZVL. Whilst there is clear evidence that ZVL is maintained by sandfly transmission, transmission may also occur by non-sandfly routes, such as congenital and sexual transmission. Dogs are the only confirmed primary reservoir of infection. Meta-analysis of dog studies confirms that infectiousness is higher in symptomatic infection; infectiousness is also higher in European than South American studies. A high prevalence of infection has been reported from an increasing number of domestic and wild mammals; updated host ranges are provided. The crab-eating fox Cerdocyon thous, opossums Didelphis spp., domestic cat Felis cattus, black rat Rattus rattus and humans can infect sandflies, but confirmation of these hosts as primary or secondary reservoirs requires further xenodiagnosis studies at the population level. Thus the putative sylvatic reservoir(s) of ZVL remains unknown. Review of intervention studies examining the effectiveness of current control methods highlights the lack of randomized controlled trials of both dog culling and residual insecticide spraying. Topical insecticides (deltamethrin-impregnated collars and pour-ons) have been shown to provide a high level of individual protection to treated dogs, but further community-level studies are needed.

PMID: 19835643 [PubMed - as supplied by publisher]

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10: BMC Cell Biol. 2009 Oct 16;10(1):74. [Epub ahead of print]

Karyopherin binding interactions and nuclear import mechanism of nuclear pore complex protein Tpr.

Ben-Efraim I, Frosst PD, Gerace L.

ABSTRACT: BACKGROUND: During the stages of the development of a potent drug candidate compounds can fail for several reasons. One of them, the efficacy of a candidate, can be estimated in silico if an appropriate ordinary differential equation model of the affected pathway is available. With such a model at hand it is also possible to detect reactions having a large effect on a certain variable such as a substance concentration. RESULTS: We show an algorithm that systematically tests the influence of activators and inhibitors of different type and strength acting at different positions in the network. The effect on a quantity to be selected (e.g. a steady state flux or concentration) is calculated. Moreover, combinations of two inhibitors or one inhibitor and one activator targeting different network positions are analysed. Furthermore, we present TIde (Target Identification), an open source, platform independent tool to investigate ordinary differential equation models in the common systems biology markup language format. It automatically assigns the respectively altered kinetics to the inhibited or activated reactions, performs the necessary calculations, and provides a graphical output of the analysis results. For illustration, TIde is used to detect optimal inhibitor positions in simple branched networks, a signalling pathway, and a well studied model of glycolysis in Trypanosoma brucei. CONCLUSIONS: Using TIde, we show in the branched models under which conditions inhibitions in a certain pathway can affect a molecule concentrations in a different. In the signalling pathway we illuminate which inhibitions have an effect on the signalling characteristics of the last active kinase. Finally, we compare our set of best targets in the glycolysis model with a similar analysis showing the applicability of our tool.

PMID: 19835572 [PubMed - as supplied by publisher]

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