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Sent on Saturday, 2011 Jul 30Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Planta Med. 2011 Jul 28. [Epub ahead of print]Structure/Antileishmanial Activity Relationship Study of Naphthoquinones and Dependency of the Mode of Action on the Substitution Patterns.Ali A, Assimopoulou AN, Papageorgiou VP, Kolodziej H.SourceFreie Universität Berlin, Institute of Pharmacy, Pharmaceutical Biology, Berlin, Germany. AbstractA series of naphthoquinones was tested for activity against both extracellular promastigote and intracellular amastigote LEISHMANIA MAJOR GFP IN VITRO. In parallel, the compounds were evaluated for cytotoxic effects against bone marrow-derived macrophages (BMM Φ) as a mammalian host cell control. Most of the compounds noticeably inhibited the growth of extracellular parasites (IC (50) 0.5 to 6 µM) and the intracellular survival of L. MAJOR GFP amastigotes (IC (50) 1 to 7 µM) when compared with the antileishmanial drug amphotericin B (IC (50) of 2.5 and 0.2 µM, respectively). In general, antiprotozoal activity and host cell cytotoxicity seemed to increase in parallel. Conspicuously, the cytotoxic effect was less pronounced on infected host cells when compared with that on noninfected cells. Concerning structure/activity relationships for the tested naphthoquinones, some interesting structural features emerged from this study. Introduction of a methyl or methoxyl group at C-2 of the parent 1,4-naphthoquinone slightly increased the antileishmanial activity against clinically relevant amastigotes, while the presence of a hydroxyl function in this position dramatically reduced the effectiveness. In contrast, hydroxylation at C-5 and dihydroxy substitution at C-5 and C-8 significantly enhanced the antiprotozoal activity. Similarly, the presence of a side chain hydroxyl group PERI to a carbonyl function as represented in the series of shikonin/alkannin derivatives increased the activity when compared with substituted analogs. Within the series of naphthoquinones tested, the dimeric mixture of vaforhizin and isovaforhizin showed the highest activity IN VITRO against the clinically relevant intracellular amastigote with an IC (50) of 1.1 µM. With IC (50) values mostly in the range of 1-3 µM, the shikonin/alkannin derivatives proved to be similarly considerably leishmanicidal. None of the compounds tested was capable to induce NO production known to play a crucial role in the host resistance against intracellular pathogens, excluding activation of microbicidal mechanisms in macrophages. The mode of action apparently depended on the substitution pattern, associated with the electrophilicity of the naphthoquinone or the efficiency of redox cycling. Conspicuously, members oxygenated in the quinone ring proved to be leishmanicidal when coincubated with glutathione, while the majority of the remaining compounds lost activity. © Georg Thieme Verlag KG Stuttgart · New York. |
| 2. | Parasitol Res. 2011 Jul 29. [Epub ahead of print]Leishmania antimony resistance: what we know what we can learn from the field.Aït-Oudhia K, Gazanion E, Vergnes B, Oury B, Sereno D.SourceEcole Nationale Supérieure Vétérinaire d'Alger, BP 161, Hassan Badi El-Harrach, Alger, Algeria. AbstractLeishmania is the causative agent of various forms of leishmaniasis, a significant cause of morbidity and mortality. The clinical manifestations of the disease range from self-healing cutaneous and mucocutaneous skin ulcers to a fatal visceral form named visceral leishmaniasis or kala-azar. In the absence of any effective vaccine, the only means to treat and control leishmaniasis is affordable medication. The treatment choice is essentially directed by economic considerations; therefore, for a large majority of countries, chemotherapy relies only on the use of cheaper antimonial compounds. The emergence of antimonial therapy failure in India linked to proven parasite resistance has stressed questions about selective factors as well as transmission risk of drug resistance. Unfortunately, in most parts of the world, the frequency of parasite antimony resistance linked to treatment failure is unknown because of a lack of information on Leishmania antimony susceptibility. This information is crucial for addressing the risk of selection and transmission of drug-resistant parasites, particularly in areas where antimony is the only chemotherapeutic alternative. However, the poor knowledge about factors that favor selection of resistant parasites, the multiplicity of the agents that can play a role in the in vivo antileishmanial activity of antimony, and the lack of a standard protocol to diagnose and survey parasite resistance all contribute to insufficient monitoring of antimony resistance. In this review, we discuss on the factors potentially involved in the selection of antimony resistance in the field and discuss on the methods available for its diagnosis. |
| 3. | J Biol Chem. 2011 Jul 28. [Epub ahead of print]The Cdc45/Mcm2-7/GINS complex in trypanosomes regulates DNA replication and interacts with two Orc1-like proteins in the origin recognition complex.Dang HQ, Li Z.SourceUniversity of Texas Medical School at Houston, United States. AbstractAccurate DNA replication requires a complex interplay of many regulatory proteins at replication origins. The CMG (Cdc45/Mcm2-7/GINS) complex, which is composed of Cdc45, Mcm2-7, and the GINS complex consisting of Sld5 and Psf1 to Psf3, is recruited by Cdc6 and Cdt1 onto origins bound by the heterohexameric origin recognition complex (ORC) and functions as a replicative helicase. Trypanosoma brucei, an early branched microbial eukaryote, appears to express an archaea-like ORC consisting of a single Orc1/Cdc6-like protein. However, unlike archaea, trypanosomes possess components of the eukaryote-like CMG complex, but whether they form an active helicase complex, associate with the ORC, and regulate DNA replication remains unknown. Here, we demonstrated that the CMG complex is formed in vivo in trypanosomes and that Mcm2-7 helicase activity is activated by the association with Cdc45 and the GINS complex in vitro. Mcm2-7 and GINS proteins are confined to the nucleus throughout the cell cycle, whereas Cdc45 is exported out of the nucleus after DNA replication, indicating that nuclear exclusion of Cdc45 constitutes one mechanism for preventing DNA re-replication in trypanosomes. With the exception of Mcm4, Mcm6, and Psf1, knockdown of individual CMG genes inhibits DNA replication and cell proliferation. Finally, we identified a novel Orc1-like protein, Orc1b, as an additional component of the ORC and showed that both Orc1b and Orc1/Cdc6 associate with Mcm2-7 via interactions with Mcm3. All together, we identified the Cdc45/Mcm2-7/GINS complex as the replicative helicase that interacts with two Orc1-like proteins in the unusual origin recognition complex in trypanosomes. |
| 4. | Eur Rev Med Pharmacol Sci. 2011 Jun;15(6):597-600.Evaluation of in vitro anti-Leishmanial activity of some brown, green and red algae from the Persian Gulf.Fouladvand M, Barazesh A, Farokhzad F, Malekizadeh H, Sartavi K.SourceThe Persian Gulf Research Center for Tropical and Infectious Medicine, The Persian Gulf Biomedical Institute, Bushehr University of Medical Sciences, Bushehr, Iran. mfooladvand39@yahoo.com AbstractBACKGROUND AND OBJECTIVES:Leishmaniasis is a protozoan parasitic disease which is transmitted by the female Phlebotomus sand fly and is prevalent in four continents.The first-choice treatment for the leishmaniasis is pentavalent antimonials, which are potentially toxic and often ineffective and use of them exhibit therapeutic failure. These pharmaceutical problems point towards the need to develop novel chemotherapeutic agents. Seaweeds are considered as source of bioactive metabolites characterized by a broad spectrum of biological activities. MATERIALS AND METHODS:In this experimental study, cold and hot water crude extracts of four species of green, brown and red marine algae "Caulerpa sertularioides, Gracilaria corticata, Gracillaria salicornia and Sargassum oligocystum" collected along the Bushehr coast of the Persian Gulf (southwest of Iran), prepared and their in vitro activities against Leishmania major promastigote were evaluated by using the MTT assay test. RESULTS:The cold and hot water crude extracts of four algae species exhibited different anti-Leishmanial activities. The minimum inhibitory concentration of hot water extracts calculated as IC50 was as follows: Caulerpa sertularioides (IC50 < or =85 microg/ml), Gracilaria corticata (IC50 < or =38 microg/ml), Gracillaria salicornia (IC50 < or =46 microg/ml) and Sargassum oligocystum (IC(50)9 < or =78 microg/ml, while these values for cold water extracts were (IC50 >125 microg/ml) for Caulerpa Sertularioides (IC50 >65 microg/ml) for Gracilaria corticata (IC50 >74 microg/ml) for Gracilaria salicornia and (IC50 >105 microg/ml) for Sargassum oligocystum, IC50 values for reference drug (Amphotericin B) was (0.16-0.2 microg/ml). DISCUSSION:According to the results, inhibitory effects of the crude extracts from these four species algae specially hot water crude extracts from "Gracilaria corticata, Gracillaria salicornia and Sargassum oligocystum" are significant and in accordance with other studies that has been done on different algae species. So these results are sufficiently promising to be followed with further studies on isolation and characterization of pure compounds from these algae species as well as in vivo experiments, a work that is already under way in our laboratory. |
| 5. | Rev Esp Quimioter. 2011 Mar;24(1):54-5.[Leishmanial parasitation of Kaposi's sarcoma in a HIV patient]. [Article in Spanish] Hinojosa MC, González MI, MartÃnez G, Ginés A. Free Article |
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| 6. | Curr Pharm Des. 2010;16(38):4194-202.Nitrosative stress during infection-induced inflammation in fish: lessons from a host-parasite infection model.Wiegertjes GF, Forlenza M.SourceDepartment of Animal Sciences, Cell Biology and Immunology Group, Wageningen Institute of Animal Sciences, Wageningen University, P.O. Box 338, 6700 AH Wageningen, The Netherlands. geert.wiegertjes@wur.nl AbstractThe inflammatory response should be considered a protective immune reaction of the host aimed at the removal of pathogens, sometimes irrespective of negative side-effects. In this review we discuss the differential contribution of macrophages and neutrophilic granulocytes to nitrosative stress in vivo and discuss how the timing and concentration of nitric oxide (NO·) are important factors determining the degree of nitrosative stress during parasite-induced inflammation. Infections of common carp (Cyprinus carpio) with the extracellular protozoan parasite Trypanoplasma borreli provide an excellent example of how adaptation and homeostasis are essential elements of the host-pathogen relationship. On the one hand, host-derived NO· interferes with clearance of IgM from the parasite surface and thus can be considered a protective immune reaction of the host. On the other hand, it is essential that the host limits the risks associated with the production of NO·, preventing suppressive effects on lymphocyte proliferation. We review, for both host and parasite, the role of oxygen and nitrogen radicals in the induction of nitrosative stress and the importance of antioxidant compounds for protection against these radicals. Finally, mediators of inflammation such as cytokines, chemokines or alarmins that are involved in the inflammatory response will be discussed in the context of the carp-T. borreli infection model. |
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