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Sent on Friday, 2011 Nov 18Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Parasite. 2011 Nov;18(4):337-339.Record of Phlebotomus (Transphlebotomus) mascittii Grassi, 1908 and Phlebotomus (Larroussius) chadlii Rioux, Juminer & Gibily, 1966 female in Algeria.Berdjane-Brouk Z, Charrel RN, Bitam I, Hamrioui B, Izri A.SourceParasitologie-Mycologie, CHU Avicenne, Université Paris 13, Bobigny, France. AbstractWe report for the first time the presence of Phlebotomus mascittii and the female of Phlebotomus chadlii in Algeria. These two species were collected during an entomological study conducted in endemic visceral leishmaniasis focus from the north part of the country, Kabylia. |
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| 2. | Parasite. 2011 Nov;18(4):333-336.Antileishmanial activity of a formulation of 2-n-propylquinoline by oral route in mice model.Campos Vieira N, Vacus J, Fournet A, Baudouin R, Bories C, Séon-Méniel B, Figadère B, Loiseau PM.SourceGroupe Chimiothérapie Antiparasitaire, UMR 8076 CNRS, Faculté de Pharmacie, Université Paris-Sud, Rue Jean-Baptiste, 92296 Châtenay-Malabry Cedex, France. Abstract2-n-propylquinoline is presently a drug-candidate for the treatment of visceral leishmaniosis in pre-clinical development. As this compound is in an oily state, it needs to be formulated and the objectives of this study are: to prepare a formulation; to demonstrate that the new salted formulation did not alter the activity of the active ingredient; and finally, that this activity was quite good compared to the reference oral drug, miltefosine. Therefore, a 2-n-propylquinoline formulation, as camphorsulfonic salt, was prepared and characterised. On the Leishmania donovani / Balb/c mice model, a treatment by oral route at 60 mmoles/kg/day for ten consecutive days with this formulation was compared to 2-n-propylquinoline alone and to miltefosine, the oral reference drug. The salt formulation did not alter the activity of the 2-n-propylquinoline. The formulation reduced the parasite burden of 76% compared to 89% for miltefosine (not significant). The characteristics of this formulation results in a suitable drugability of 2-n-propylquinoline for further studies. |
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| 3. | Parasite. 2011 Nov;18(4):303-309.[Entomological survey in the historical sleeping sickness focus of Bendje (Gabon).] [Article in French] Kohagne Tongué L, Gounoue Kamkuimo R, Mengue M'eyi P, Kaba D, Louis FJ, Mimpfoundi R.SourceOrganisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), BP 15665, Yaoundé, Cameroun. lisette_oceac@yahoo.fr. AbstractThe situation of human African trypanosomiasis (sleeping sickness) is poorly known in Gabon. Most of the historical foci have not been investigated for more than 15 years. Few cases are passively recorded from the historical focus of Bendjé; they involved mainly fishermen but determining their contamination site is difficult because of their mobility due to their activity. The presence of these cases in that focus could favour its reactivation if the vector is still there. In order to assess a potential transmission risk in that area, an entomological survey has been carried out in it. Traps were set up during four days in different habitats used by humans during their daily activities. Three species of tsetse flies (Glossina palpalis palpalis, G. pallicera newsteadi and G. caliginea) were caught and two species of trypanosomes (Trypanosoma vivax and T. brucei s.l.) were identified by PCR. These results suggest the presence of an animal transmission cycle. Human-flies contact was confirmed in all type of habitats but no transmission was quantified in the mangrove. |
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| 4. | Parasite. 2011 Nov;18(4):295-302.Experimental evaluation of xenodiagnosis to detect trypanosomes at low parasitaemia levels in infected hosts.Wombou Toukam CM, Solano P, Bengaly Z, Jamonneau V, Bucheton B.SourceCentre international de recherche-développement sur l'élevage en zone subhumide (CIRDES), 01 BP 454 Bobo-Dioulasso 01, Burkina Faso. AbstractIn Human African Trypanosomosis (HAT) endemic areas, there are a number of subjects that are positive to serological tests but in whom trypanosomes are difficult to detect with the available parasitological tests. In most cases and particularly in West Africa, these subjects remain untreated, thus posing a fundamental problem both at the individual level (because of a possible lethal evolution of the disease) and at the epidemiological level (since they are potential reservoirs of trypanosomes). Xenodiagnosis may constitute an alternative for this type of cases. The objective of this study was to update the use of xenodiagnosis to detect trypanosomes in infected host characterized by low parasitaemia levels. This was carried out experimentally by infecting cattle and pigs with Trypanosoma congolense and T. brucei gambiense respectively, and by feeding tsetse flies (Glossina morsitans submorsitans and G. palpalis gambiensis, from the CIRDES colonies) on these animals at a time when the observed blood parasitaemia were low or undetectable by the classical microscopic parasitological tests used for the monitoring of infected animals. Our results showed that: i) the G. p. gambiensis colony at CIRDES could not be infected with the T. b. gambiense stocks used; ii) midgut infections of G. m. submorsitans were observed with both T. congolense and T. b. gambiense; iii) xenodiagnosis remains positive even at very low blood parasitaemia for both T. congolense and T. b. gambiense; and iv) to implement T. b. gambiense xenodiagnosis, batches of 20 G. m. submorsitans should be dissected two days after the infective meal. These results constitute a first step toward a possible implementation of xenodiagnosis to better characterize the parasitological status of seropositive individuals and the modalities of parasite transmission in HAT foci. |
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| 5. | Mol Biol Int. 2011;2011:876021. Epub 2011 Jun 13.Antiproliferative, Ultrastructural, and Physiological Effects of Amiodarone on Promastigote and Amastigote Forms of Leishmania amazonensis.de Macedo-Silva ST, de Oliveira Silva TL, Urbina JA, de Souza W, Rodrigues JC.SourceLaboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas, 373, CCS, Ilha do Fundão, 21941-902 Rio de Janeiro, Brazil. AbstractAmiodarone (AMIO), the most frequently antiarrhythmic drug used for the symptomatic treatment of chronic Chagas' disease patients with cardiac compromise, has recently been shown to have also specific activity against fungi, Trypanosoma cruzi and Leishmania. In this work, we characterized the effects of AMIO on proliferation, mitochondrial physiology, and ultrastructure of Leishmania amazonensis promastigotes and intracellular amastigotes. The IC(50) values were 4.21 and 0.46 μM against promastigotes and intracellular amastigotes, respectively, indicating high selectivity for the clinically relevant stage. We also found that treatment with AMIO leads to a collapse of the mitochondrial membrane potential (ΔΨm) and to an increase in the production of reactive oxygen species, in a dose-dependent manner. Fluorescence microscopy of cells labeled with JC-1, a marker for mitochondrial energization, and transmission electron microscopy confirmed severe alterations of the mitochondrion, including intense swelling and modification of its membranes. Other ultrastructural alterations included (1) presence of numerous lipid-storage bodies, (2) presence of large autophagosomes containing part of the cytoplasm and membrane profiles, sometimes in close association with the mitochondrion and endoplasmic reticulum, and (3) alterations in the chromatin condensation and plasma membrane integrity. Taken together, our results indicate that AMIO is a potent inhibitor of L. amazonensis growth, acting through irreversible alterations in the mitochondrial structure and function, which lead to cell death by necrosis, apoptosis and/or autophagy. |
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| 6. | Mol Biol Int. 2011;2011:854626. Epub 2011 May 4.Peptide Inhibition of Topoisomerase IB from Plasmodium falciparum.Roy A, D'Annessa I, Nielsen CJ, Tordrup D, Laursen RR, Knudsen BR, Desideri A, Andersen FF.SourceDepartment of Molecular Biology and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, C.F. Møllers Allé 3, Building 1130, 8000 Aarhus C, Denmark. AbstractControl of diseases inflicted by protozoan parasites such as Leishmania, Trypanosoma, and Plasmodium, which pose a serious threat to human health worldwide, depends on a rather small number of antiparasite drugs, of which many are toxic and/or inefficient. Moreover, the increasing occurrence of drug-resistant parasites emphasizes the need for new and effective antiprotozoan drugs. In the current study, we describe a synthetic peptide, WRWYCRCK, with inhibitory effect on the essential enzyme topoisomerase I from the malaria-causing parasite Plasmodium falciparum. The peptide inhibits specifically the transition from noncovalent to covalent DNA binding of P. falciparum topoisomerase I, while it does not affect the ligation step of catalysis. A mechanistic explanation for this inhibition is provided by molecular docking analyses. Taken together the presented results suggest that synthetic peptides may represent a new class of potential antiprotozoan drugs. |
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| 7. | Mol Biol Int. 2011;2011:782971. Epub 2011 Jun 5.Role of cAMP Signaling in the Survival and Infectivity of the Protozoan Parasite, Leishmania donovani.Biswas A, Bhattacharya A, Das PK.SourceMolecular Cell Biology Laboratory, Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Kolkata 700032, India. AbstractLeishmania donovani, while invading macrophages, encounters striking shift in temperature and pH (from 22°C and pH 7.2 to 37°C and pH 5.5), which act as the key environmental trigger for differentiation, and increases cAMP level and cAMP-mediated responses. For comprehensive understanding of cAMP signaling, we studied the enzymes related to cAMP metabolism. A stage-specific and developmentally regulated isoform of receptor adenylate cyclase (LdRACA) showed to regulate differentiation-coupled induction of cAMP. The soluble acidocalcisomal pyrophosphatase, Ldvsp1, was the major isoform regulating cAMP level in association with LdRACA. A differentially expressed soluble cytosolic cAMP phosphodiesterase (LdPDEA) might be related to infection establishment by shifting trypanothione pool utilization bias toward antioxidant defense. We identified and cloned a functional cAMP-binding effector molecule from L. donovani (a regulatory subunit of cAMP-dependent protein kinase, LdPKAR) that may modulate metacyclogenesis through induction of autophagy. This study reveals the significance of cAMP signaling in parasite survival and infectivity. |
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| 8. | Mol Biol Int. 2011;2011:571242. Epub 2011 Jun 8.Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions.< /h1>Haldar AK, Sen P, Roy S.SourceDivision of Infectious Diseases and Immunology, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4 Raja S. C. Mullick Road, Kolkata West Bengal 700032, India. AbstractIn the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V) in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistant Leishmania donovani isolates in murine model. Thus, vanadium compounds may be used in combination with Sb(V) in the treatment of Sb(V) resistance cases of kala-azar. |
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| 9. | Mol Biol Int. 2011;2011:532106. Epub 2011 Jul 25.A Perspective on the Emergence of Sialic Acids as Potent Determinants Affecting Leishmania Biology.Ghoshal A, Mandal C.SourceInfectious Diseases and Immunology Division, Council of Scientific and Industrial Research, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700032, India. AbstractLeishmaniasis caused by Leishmania sp. has a wide range of manifestations from cutaneous to the deadly visceral form. They shuttle between the invertebrate and vertebrate hosts as promastigotes and amastigotes having adaptations for subverting host immune responses. Parasite-specific glycoconjugates have served as important determinants influencing parasite recognition, internalization, differentiation, multiplication, and virulence. Despite the steady progress in the field of parasite glycobiology, sialobiology has been a less traversed domain of research in leishmaniasis. The present paper focuses on identification, characterization, and differential distribution of sialoglycotope having the linkage-specific 9-O-acetylated sialic acid in promastigotes of different Leishmania sp. causing different clinical ramifications emphasizing possible role of these sialoglycotopes in infectivity, virulence, nitric oxide resistance, and host modulation in Leishmania spp. asserting them to be important molecules influencing parasite biology. |
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| 10. | Mol Biol Int. 2011;2011:428486. Epub 2011 Jun 26.Identification and Characterization of Genes Involved in Leishmania Pathogenesis: The Potential for Drug Target Selection.Duncan R, Gannavaram S, Dey R, Debrabant A, Lakhal-Naouar I, Nakhasi HL.SourceDivision of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, FDA, Bethesda, MD 20852, USA. AbstractIdentifying and characterizing Leishmania donovani genes and the proteins they encode for their role in pathogenesis can reveal the value of this approach for finding new drug targets. Effective drug targets are likely to be proteins differentially expressed or required in the amastigote life cycle stage found in the patient. Several examples and their potential for chemotherapeutic disruption are presented. A pathway nearly ubiquitous in living cells targeted by anticancer drugs, the ubiquitin system, is examined. New findings in ubiquitin and ubiquitin-like modifiers in Leishmania show how disruption of those pathways could point to additional drug targets. The programmed cell death pathway, now recognized among protozoan parasites, is reviewed for some of its components and evidence that suggests they could be targeted for antiparasitic drug therapy. Finally, the endoplasmic reticulum quality control system is involved in secretion of many virulence factors. How disruptions in this pathway reduce virulence as evidence for potential drug targets is presented. |
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