What's new for 'Trypanosomatids' in PubMed

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Sent on Friday, 2012 March 09
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.	Dermatol Online J. 2012 Feb 15;18(2):4. Clinical spectrum of cutaneous leishmaniasis: An overview from Pakistan. Bari AU. Source Department of Dermatology, CMH, Peshawar, Pakistan. Abstract The clinical spectrum of leishmaniasis encompasses subclinical (inapparent), localized (skin lesions), and disseminated infection (cutaneous, mucosal, or visceral). The clinico-pathological picture of cutaneous leishmaniasis is variable and depends not only on the leishmania species but also on endemic region, host factors, and immuno-inflammatory responses. Symptomatic disease is subacute or chronic and diverse in presentation and outcome. Pakistan is one of the countries in which cutaneous leishmaniasis is becoming an epidemic disease and because of its morbidity and disfiguring scars, it is considered a serious public health problem. This is an attempt to review the clinical spectrum of old world cutaneous leishmaniasis, classical and unusual clinical presentations, occurring in Pakistan.
	PMID: 22398225 [PubMed - in process]

2.	Rev Neurol (Paris). 2012 Mar 5. [Epub ahead of print] [Sleeping sickness: End of the epidemic outbreak?] [Article in French] Bisser S, Courtioux B. Source Inserm UMR 1094, neuroépidémiologie tropicale, CNRS FR 3503 GEIST, faculté de pharmacie, institut d'épidémiologie neurologique et de neurologie tropicale, université Limoges, 87025 Limoges, France. Abstract Sleeping sickness or human African trypanosomiasis is a parasitic disease transmitted by tsetse flies and therefore confined to its habitat, the central part of the African continent. Two disease forms are linked to two different parasites: T. b. gambiense and T. b. rhodesiense. Actual epidemiological data and precise and dynamic mapping of foci are in favor of a real decrease of the disease. Not all areas are under control and resurgence can still not be avoided from the remote areas where the disease is endemic. However, recent advances in knowledge in parasite genetics are giving hope of control. In 2009, for the first time since 50 years, less than 10,000 cases were declared to the World Health Organization. Clinical trials allowed revising some clinical concepts and linking them with parasite genetics: both disease forms can show variations from asymptomatic, chronic to acute and are linked to genetic differences in the host or the parasite. Parasitological diagnosis may be facilitated by the introduction of individual rapid tests and PCR-based field tests. Knowledge in mechanisms of brain invasion and screenings of inflammatory molecules allow new marker combinations for staging but they do not avoid lumbar puncture. Therapeutic options remain limited but there is hope to develop a new drug orally available in a near future. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
	PMID: 22398218 [PubMed - as supplied by publisher]

3.	Int J Antimicrob Agents. 2012 Mar 5. [Epub ahead of print] In vitro evaluation of bisnaphthalimidopropyl derivatives loaded into pegylated nanoparticles against Leishmania infantum protozoa. Costa Lima S, Rodrigues V, Garrido J, Borges F, Kong Thoo Lin P, Cordeiro da Silva A. Source Parasite Disease Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal. Abstract Bisnaphthalimidopropyl (BNIP) derivatives have recently been shown to have potential as antileishmanial agents. However, these compounds have some drawbacks, including their low aqueous solubility and some toxic effects. In this study, we designed a drug delivery system for enhanced delivery of BNIP derivative compounds whilst reducing adverse toxic effects, and hence increasing their biological efficacy. A coated drug delivery system based on polymeric nanoparticles of pegylated poly(lactic acid) (PLA), a biodegradable polymer, was successfully achieved. The pegylated PLA nanoformulations loaded with BNIP derivatives were evaluated in an in vitro model of intracellular amastigotes in murine J774 and human THP-1 cells for visceral leishmaniasis using luciferase-expressing Leishmania infantum parasites. Pegylation of PLA nanoparticles significantly reduced the capacity of empty nanoparticles in inhibiting intracellular parasite growth. The BNIP derivatives BNIPDadec and BNIPDaoct exhibited EC(50) values (concentration of compound necessary to decrease cell viability to 50% of the untreated control) of ca. 4.5μM for THP-1 and J774 cells and ca. 9.0μM for mouse bone marrow-derived macrophages. Nanoparticle encapsulation of the BNIP derivative compounds decreased their toxicity towards macrophages by ≥10-fold as evaluated by the MTT assay. The antileishmanial activity of free BNIPDadec was 1.02±0.41μM and 0.73±0.06μM for THP-1 and J774 macrophages, respectively. Pegylation of PLA nanoparticles loaded with BNIPDadec resulted in EC(50) values of 1.43±0.63μM and 1.79±0.77μM for THP-1 and J774 macrophages, respectively. A similar trend was observed for free BNIPDaoct and pegylated BNIPDaoct PLA nanoparticles (2.43±0.19μM and 1.23±0.40μM for THP-1 macrophages and 1.36±0.17μM and 1.52±0.57μM for J774 macrophages). The nanoformulations were more efficient in reducing parasitic growth inside human macrophages than in murine cells, suggesting host cell-dependent metabolism. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
	PMID: 22398197 [PubMed - as supplied by publisher]

4.	Biomed Pharmacother. 2012 Feb 17. [Epub ahead of print] Preparation and antiprotozoal evaluation of promising β-carboline alkaloids. Gellis A, Dumètre A, Lanzada G, Hutter S, Ollivier E, Vanelle P, Azas N. Source UMR CNRS 6264, laboratoire chimie provence, Aix-Marseille université-laboratoire de pharmacochimie radicalaire, faculté de pharmacie, 27, boulevard Jean-Moulin, 13385 Marseille cedex 05, France. Abstract The synthesis of β-carbolines and their in vitro antiplasmodial and antileishmanial activities were described herein. These molecules have also been studied concerning their in vitro cytotoxicity toward the human cell line THP1, in order to calculate their respective selectivity indexes (SI). Among the 20 tested molecules, four exhibited significant antiplasmodial activity on the W2 multi-resistant Plasmodium falciparum strain (0.7<IC(50)<1.7μM), in comparison with two references drugs (chloroquine and doxycycline), and a low cytotoxicity. These β-carbolines were also evaluated concerning their in vitro antileshmanial activity on Leishmania donovani promastigotes, permitting to identify an antileshmanial hit compound, displaying quite promising activity (IC(50)=6.1μM) in comparison with amphotericin B and pentamidine chosen as reference drugs. Finally, structure-activity relationships were discussed, pointing out that molecules presenting a para-substituted phenyl moiety at position 1 of the β-carboline ring displayed the best biological profile. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
	PMID: 22397756 [PubMed - as supplied by publisher]

5.	Parasit Vectors. 2012 Mar 7;5(1):46. [Epub ahead of print] Insecticide resistance in the sand fly, Phlebotomus papatasi from Khartoum State, Sudan. Hassan MM, Widaa SO, Osman OM, Numiary MS, Ibrahim MA, Abushama HM. Abstract ABSTRACT: BACKGROUND: Phlebotomus papatasi the vector of cutaneous leishmaniasis (CL) is the most widely spread sand fly in Sudan. No data has previously been collected on insecticide susceptibility and/or resistance of this vector, and a first study to establish a baseline data is reported here. METHODS: Sand flies were collected from Surogia village, (Khartoum State), Rahad Game Reserve (eastern Sudan) and White Nile area (Central Sudan) using light traps. Sand flies were reared in Tropical Medicine Research Institute laboratory. The insecticide susceptibility status of first progeny (F1) of P. papatasi of each population was tested using WHO insecticide kits. Also, P. papatasi specimens from Surogia village and Rahad Game Reserve were assayed for activities of enzyme systems involved in insecticide resistance (acetylcholinesterase (AChE), non-specific carboxylesterases (EST), glutathione-S-transferases (GSTs) and cytochrome p450 monooxygenases (Cyt p450). RESULTS: Populations of P. papatasi from White Nile and Rahad Game Reserve were sensitive to dichlorodiphenyltrichloroethane (DDT), permethrin, malathion, and propoxur. However, P. papatasi population from Surogia village was sensitive to DDT and permethrin but highly resistant to malathion and propoxur. Furthermore, P. papatasi of Surogia village had significantly higher insecticide detoxification enzyme activity than of those of Rahad Game Reserve. The sand fly population in Surogia displayed high AChE activity and only three specimens had elevated levels for EST and GST. CONCLUSIONS: The study provided evidence for malathion and propoxur resistance in sand fly population of Surogia village, which probably resulted from anti-malarial control activities carried out in the area during the past 50 years.
	PMID: 22397726 [PubMed - as supplied by publisher]

6.	Expert Rev Anti Infect Ther. 2012 Mar;10(3):261-4. Targets for immunochemotherapy in leishmaniasis. Mukhopadhyay D, Saha P, Chatterjee M. Source Department of Pharmacology, Institute of Postgraduate Medical Education & Research, 244 B Acharya JC Bose Road, Kolkata 700 020, India.
	PMID: 22397558 [PubMed - in process]

7.	Biochemistry. 2012 Jan 10;51(1):265-72. Epub 2011 Dec 16. Flavin-linked Erv-family sulfhydryl oxidases release superoxide anion during catalytic turnover. Daithankar VN, Wang W, Trujillo JR, Thorpe C. Source Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716-2522, United States. Abstract Typically, simple flavoprotein oxidases couple the oxidation of their substrates with the formation of hydrogen peroxide without release of significant levels of the superoxide ion. However, two evolutionarily related single-domain sulfhydryl oxidases (Erv2p; a yeast endoplasmic reticulum resident protein and augmenter of liver regeneration, ALR, an enzyme predominantly found in the mitochondrial intermembrane) release up to ~30% of the oxygen they reduce as the superoxide ion. Both enzymes oxidize dithiol substrates via a redox-active disulfide adjacent to the flavin cofactor within the helix-rich Erv domain. Subsequent reduction of the flavin is followed by transfer of reducing equivalents to molecular oxygen. Superoxide release was initially detected using tris(3-hydroxypropyl)phosphine (THP) as an alternative reducing substrate to dithiothreitol (DTT). THP, and other phosphines, showed anomalously high turnover numbers with Erv2p and ALR in the oxygen electrode, but oxygen consumption was drastically suppressed upon the addition of superoxide dismutase. The superoxide ion initiates a radical chain reaction promoting the aerobic oxidation of phosphines with the formation of hydrogen peroxide. Use of a known flux of superoxide generated by the xanthine/xanthine oxidase system showed that one superoxide ion stimulates the reduction of 27 and 4.5 molecules of oxygen using THP and tris(2-carboxyethyl)phosphine (TCEP), respectively. This superoxide-dependent amplification of oxygen consumption by phosphines provides a new kinetic method for the detection of superoxide. Superoxide release was also observed by a standard chemiluminescence method using a luciferin analogue (MCLA) when 2 mM DTT was employed as a substrate of Erv2p and ALR. The percentage of superoxide released from Erv2p increased to ~65% when monomeric mutants of the normally homodimeric enzyme were used. In contrast, monomeric multidomain quiescin sulfhydryl oxidase enzymes that also contain an Erv FAD-binding fold release only 1-5% of their total reduced oxygen species as the superoxide ion. Aspects of the mechanism and possible physiological significance of superoxide release from these Erv-domain flavoproteins are discussed. PMCID: PMC3254808 [Available on 2013/1/10]
	PMID: 22148553 [PubMed - indexed for MEDLINE]
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