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Sent on Saturday, 2011 Aug 13Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Exp Parasitol. 2011 Aug 3. [Epub ahead of print]Immunogenicity of Leishmania donovani iron superoxide dismutase B1 and peroxidoxin 4 in BALB/c mice: The contribution of Toll-like receptor agonists as adjuvant.Daifalla NS, Bayih AG, Gedamu L.SourceUniversity of Calgary, Department of Biological Sciences, Room 374, 2500 University Drive NW, Calgary, AB, Canada T2N 1N4. AbstractIn this study, we assessed the immune response of two Leishmania donovani recombinant proteins: iron superoxide dismutase B1 (SODB1) and peroxidoxin 4 (Pxn4) in BALB/c mice. Assessment of the immunogenicity of these proteins alone or combined with Toll-like receptor 9 (TLR-9) agonist (CpG ODN) or TLR-4 agonist (GLA-SE) showed that they elicit specific antibody as well as cytokine production in response to the respective antigen in vitro. The use of adjuvants augmented immunogenicity of these antigens and more importantly, skewed the immune response to a Th1-type. These results indicate that recombinant SODB1 and Pxn4 proteins are potential vaccine candidates when administered with appropriate adjuvants. Copyright © 2011 Elsevier Inc. All rights reserved. |
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| 2. | Parasit Vectors. 2011 Aug 11;4(1):159. [Epub ahead of print]First detection of Leishmania killicki (Kinetoplastida, Trypanosomatidae) in Ctenodactylus gundi (Rodentia, Ctenodactylidae), a possible reservoir of human cutaneous leishmaniasis in Tunisia.Jaouadi K, Haouas N, Chaara D, Gorcii M, Chargui N, Augot D, Pratlong F, Dedet JP, Ettlijani S, Mezhoud H, Babba H.AbstractABSTRACT: BACKGROUND:Leishmania killicki was originally described in 1980 in southeast Tunisia. It was also recently reported in Lybia and Algeria. Nevertheless, neither vector nor reservoirs of this parasite are known. The identification of the vector and the animal reservoir host of L. killicki is critical for the establishment of an efficient control strategy. FINDINGS:blood, popliteal lymph node, spleen, bone marrow, liver and skin were collected from 50 rodents in 2009 in south western Tunisia. Samples were smeared onto glass slides, cultured on NNN medium and tested by polymerase chain reaction for Leishmania detection. Parasites were detected by PCR from 10 Psammomys obesus and from two Ctenodactylus gundi. Parasite identification was performed simultaneously by internal transcribed spacer 1 PCR-RFLP and by PCR sequencing. Both Leishmania major and Leishmania killicki were identified from infected Psammomys and Ctenodactylus gundi respectively. CONCLUSION:This is the first report of Leishmania killicki identified from Ctenodactylus gundi in Tunisia. This result supports the assumption that C. gundi is a potential reservoir for Leishmania killicki. |
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| 3. | Biochem J. 2011 Sep 1;438(2):229-44.Polyamine homoeostasis as a drug target in pathogenic protozoa: peculiarities and possibilities.Birkholtz LM, Williams M, Niemand J, Louw AI, Persson L, Heby O.Source*Department of Biochemistry, University of Pretoria, Private Bag X20, Hatfield 0028, South Africa. AbstractNew drugs are urgently needed for the treatment of tropical and subtropical parasitic diseases, such as African sleeping sickness, Chagas' disease, leishmaniasis and malaria. Enzymes in polyamine biosynthesis and thiol metabolism, as well as polyamine transporters, are potential drug targets within these organisms. In the present review, the current knowledge of unique properties of polyamine metabolism in these parasites is outlined. These properties include prozyme regulation of AdoMetDC (S-adenosylmethionine decarboxylase) activity in trypanosomatids, co-expression of ODC (ornithine decarboxylase) and AdoMetDC activities in a single protein in plasmodia, and formation of trypanothione, a unique compound linking polyamine and thiol metabolism in trypanosomatids. Particularly interesting features within polyamine metabolism in these parasites are highlighted for their potential in selective therapeutic strategies. |
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| 4. | Nat Prod Commun. 2011 Jul;6(7):973-6.Activity of Cuban propolis extracts on Leishmania amazo nensis and Trichomonas vaginalis.Monzote Fidalgo L, Sariego Ramos I, García Parra M, Cuesta-Rubio O, Márquez Hernández I, Campo Fernández M, Piccinelli AL, Rastrelli L.SourceParasitology Department, Institute of Tropical Medicine "Pedro Kouri", Havana City, Cuba. monzote@ipk.sld.cu AbstractIn this paper we analyzed the antiprotozoal effects of eighteen Cuban propolis extracts (brown, red and yellow type) collected in different geographic areas, using Leishmania amazonensis (as a model of intracellular protozoa) and Trichomonas vaginalis (as a model of extracellular protozoa). All evaluated propolis extracts caused inhibitory effect on intracellular amastigotes of L. amazonensis. However, cytotoxicity on peritoneal macrophages from BALB/c mice was observed. Only five samples decreased the viability of T. vaginalis trophozoites at concentrations lower than 10 microg/mL. No correlation between the type of propolis and antiprotozoal activity was found. Cuban propolis extracts demonstrated activity against both intracellular and extracellular protozoa model, as well as the potentialities of propolis as a natural source to obtain new antiprotozoal agents. |
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| 5. | ChemMedChem. 2011 Aug 10. doi: 10.1002/cmdc.201100278. [Epub ahead of print]Optimisation of the Anti-Trypanosoma brucei Activity of the Opioid Agonist U50488.Smith VC, Cleghorn LA, Woodland A, Spinks D, Hallyburton I, Collie IT, Yi Mok N, Norval S, Brenk R, Fairlamb AH, Frearson JA, Read KD, Gilbert IH, Wyatt PG.SourceDrug Discovery Unit, College of Life Sciences, James Black Centre, University of Dundee, Dundee, DD1 5EH, Scotland (UK). AbstractScreening of the Sigma-Aldrich Library of Pharmacologically Active Compounds (LOPAC) against cultured Trypanosoma brucei, the causative agent of African sleeping sickness, resulted in the identification of a number of compounds with selective antiproliferative activity over mammalian cells. These included (+)-(1R,2R)-U50488, a weak opioid agonist with an EC(50) value of 59 nM as determined in our T. brucei in vitro assay reported previously. This paper describes the modification of key structural elements of U50488 to investigate structure-activity relationships (SAR) and to optimise the antiproliferative activity and pharmacokinetic properties of this compound. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
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| 6. | Amino Acids. 2011 Aug 11. [Epub ahead of print]A gold-containing drug against parasitic polyamine metabolism: the X-ray structure of trypanothione reductase from Leishmania infantum in complex with auranofin reveals a dual mechanism of enzyme inhibition.Ilari A, Baiocco P, Messori L, Fiorillo A, Boffi A, Gramiccia M, Di Muccio T, Colotti G.SourceDepartment of Biochemical Sciences, Institute of Molecular Biology and Pathology CNR, Sapienza University of Rome, P.le A. Moro 5, 00185, Rome, Italy, Andrea.ilari@uniroma1.it. AbstractAuranofin is a gold(I)-containing drug in clinical use as an antiarthritic agent. Recent studies showed that auranofin manifests interesting antiparasitic actions very likely arising from inhibition of parasitic enzymes involved in the control of the redox metabolism. Trypanothione reductase is a key enzyme of Leishmania infantum polyamine-dependent redox metabolism, and a validated target for antileishmanial drugs. As trypanothione reductase contains a dithiol motif at its active site and gold(I) compounds are known to be highly thiophilic, we explored whether auranofin might behave as an effective enzyme inhibitor and as a potential antileishmanial agent. Notably, enzymatic assays revealed that auranofin causes indeed a pronounced enzyme inhibition. To gain a deeper insight into the molecular basis of enzyme inhibition, crystals of the auranofin-bound enzyme, in the presence of NADPH, were prepared, and the X-ray crystal structure of the auranofin-trypanothione reductase-NADPH complex was solved at 3.5 Å resolution. In spite of the rather low resolution, these data were of sufficient quality as to identify the presence of the gold center and of the thiosugar of auranofin, and to locate them within the overall protein structure. Gold binds to the two active site cysteine residues of TR, i.e. Cys52 and Cys57, while the thiosugar moiety of auranofin binds to the trypanothione binding site; thus auranofin appears to inhibit TR through a dual mechanism. Auranofin kills the promastigote stage of L. infantum at micromolar concentration; these findings will contribute to the design of new drugs against leishmaniasis. |
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| 7. | Int J Clin Pharm. 2011 Jul 22. [Epub ahead of print]A rare case of Visceral leishmaniasis with multiple relapse and multi-drug unresponsive: successfully treated with combination therapy.Kumar N, Sinha PK, Pandey K, Verma N, Lal CS, Ranjan A, Verma RB, Das P.SourceDivision of Clinical Medicine, RMRIMS (ICMR), Agamkuan, Patna, Bihar, 800 007, India, drnawinkumar@gmail.com. AbstractCase We report a 32-year old relapse case of Visceral leishmaniasis, treated with Paromomycin who belonged from a endemic zone of Bihar state, India. After confirmation, he was treated with Amphotericin B, followed by Liposomal Amphotericin B in full course and even in higher dose. But after each therapy, the patient either did not responded or relapsed after treatment. Ultimately, the patient was successfully treated with combination therapy of Liposomal amphotericin B and Miltefosine without any relapse. Conclusion The multi-drug unresponsive Visceral leishmaniasis cases could pose a major threat to treatment strategy in the elimination program. In such situation, combination therapy seems to be a better approach that needs to be explored. |
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| 8. | Clin Infect Dis. 2011 Aug 10. [Epub ahead of print]Patterns of Illness in Travelers Visiting Mexico and Central America: The GeoSentinel Experience.Flores-Figueroa J, Okhuysen PC, von Sonnenburg F, Dupont HL, Libman MD, Keystone JS, Hale DC, Burchard G, Han PV, Wilder-Smith A, Freedman DO; for the GeoSentinel Surveillance Network.SourceCenter for Infectious Diseases, School of Public Health, Houston, Texas. AbstractBackground. Mexico and Central America are important travel destinations for North American and European travelers. There is limited information on regional differences in travel related morbidity. Methods. We describe the morbidity among 4779 ill travelers returned from Mexico and Central America who were evaluated at GeoSentinel network clinics during December 1996 to February 2010. Results. The most frequent presenting syndromes included acute and chronic diarrhea, dermatologic diseases, febrile systemic illness, and respiratory disease. A higher proportion of ill travelers from the United States had acute diarrhea, compared with their Canadian and European counterparts (odds ratio, 1.9; P < .0001). During the 2009 H1N1 influenza outbreak from March 2009 through February 2010, the proportionate morbidity (PM) associated with respiratory illnesses in ill travelers increased among those returned from Mexico, compared with prior years (196.0 cases per 1000 ill returned travelers vs 53.7 cases per 1000 ill returned travelers; P < .0001); the PM remained constant in the rest of Central America (57.3 cases per 1000 ill returned travelers). We identified 50 travelers returned from Mexico and Central America who developed influenza, including infection due to 2009 H1N1 strains and influenza-like illness. The overall risk of malaria was low; only 4 cases of malaria were acquired in Mexico (PM, 2.2 cases per 1000 ill returned travelers) in 13 years, compared with 18 from Honduras (PM, 79.6 cases per 1000 ill returned travelers) and 14 from Guatemala (PM, 34.4 cases per 1000 ill returned travelers) during the same period. Plasmodium vivax malaria was the most frequent malaria diagnosis. Conclusions. Travel medicine practitioners advising and treating travelers visiting these regions should dedicate special attention to vaccine-preventable illnesses and should consider the uncommon occurrence of acute hepatitis A, leptospirosis, neurocysticercosis, acute Chagas disease, onchocerciasis, mucocutaneous leishmaniasis, neurocysticercosis, HIV, malaria, and brucellosis. |
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| 9. | Clin Vaccine Immunol. 2011 Aug 10. [Epub ahead of print]TH1/TH2 CYTOKINE PROFILE IN HIV AND LEISHMANIA CO-INFECTED PATIENTS IN BRAZIL.Rodrigues MZ, Grassi MF, Mehta S, Zhang XQ, Gois LL, Schooley RT, Badaro R.SourceFederal University of Bahia, Salvador, Bahia, Brazil. AbstractTo evaluate the effects of HIV on immune responses in cutaneous leishmaniasis (CL), we quantified cytokine levels from plasma and stimulated PBMCs from individuals infected with HIV and/or CL. IFN-γ, IL-13, and the ratio of IFN-γ/IL-10 produced in response to stimulation with soluble Leishmania antigens were significantly lower in HIV/Leishmania co-infected patients. |
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| 10. | Phytomedicine. 2011 Aug 8. [Epub ahead of print]Cytotoxic activity of secondary metabolites derived from Artemisia annua L. towards cancer cells in comparison to its designated active constituent artemisinin.Efferth T, Herrmann F, Tahrani A, Wink M.SourceDepartment of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany. AbstractArtemisia annua L. (sweet wormwood, qinhao) has traditionally been used in Chinese medicine. The isolation of artemisinin from Artemisia annua and its worldwide accepted application in malaria therapy is one of the showcase success stories of phytomedicine during the past decades. Artemisinin-type compounds are also active towards other protozoal or viral diseases as well as cancer cells in vitro and in vivo. Nowadays, Artemisia annua tea is used as a self-reliant treatment in developing countries. The unsupervised use of Artemisia annua tea has been criticized to foster the development of artemisinin resistance in malaria and cancer due to insufficient artemisinin amounts in the plant as compared to standardized tablets with isolated artemisinin or semisynthetic artemisinin derivatives. However, artemisinin is not the only bioactive compound in Artemisia annua. In the present investigation, we analyzed different Artemisia annua extracts. Dichloromethane extracts were more cytotoxic (range of IC(50): 1.8-14.4μg/ml) than methanol extracts towards Trypanosoma b. brucei (TC221 cells). The range of IC(50) values for HeLa cancer cells was 54.1-275.5μg/ml for dichloromethane extracts and 276.3-1540.8μg/ml for methanol extracts. Cancer and trypanosomal cells did not reveal cross-resistance among other compounds of Artemisia annua, namely the artemisinin-related artemisitene and arteanuine B as well as the unrelated compounds, scopoletin and 1,8-cineole. This indicates that cells resistant to one compound retained sensitivity to another one. These results were also supported by microarray-based mRNA expression profiling showing that molecular determinants of sensitivity and resistance were different between artemisinin and the other phytochemicals investigated. Copyright © 2011 Elsevier GmbH. All rights reserved. |
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