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 10

1.	Arch Pharm (Weinheim). 2011 Jan;344(1):50-5. doi: 10.1002/ardp.201000148. Epub 2010 Nov 25. Antimicrobial and antineoplastic activities of agelasine analogs modified in the purine 2-position. Roggen H, Charnock C, Burman R, Felth J, Larsson R, Bohlin L, Gundersen LL. Department of Chemistry, University of Oslo, Blindern, Oslo, Norway. Abstract Agelasines are 7,9-dialkylpurinium salts found in marine sponges (Agelas sp.), which display a variety of antimicrobial and cytotoxic effects. We have synthesized simplified agelasine analogs modified in the purine 2-position and examined their antimicrobial and anticancer activities. The compounds were screened against Staphylococcus aureus, Escherichia coli, Mycobacterium tuberculosis, Candida krusei, and Candida albicans, protozoa causing tropical diseases (Plasmodium falciparum, Leishmania infantum, Trypanosoma cruzi, and Trypanosoma brucei), a panel of human cancer cell lines (U-937 GTB, RPMI 8226/s, CEM/s, and ACHN) as well as VERO and/or MRC-5 cells. The results indicate that the introduction of a methyl group in the purine 2-position is beneficial for antimycobacterial and antiprotozoal activity, and that amino groups may enhance activity against several cancer cell lines. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
	PMID: 21213351 [PubMed - in process]
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2.	Parasitol Res. 2011 Jan 7. [Epub ahead of print] Antileishmanial efficacy of fluconazole and miltefosine in combination with an immunomodulator-picroliv. Shakya N, Sane SA, Gupta S. Division of Parasitology, Central Drug Research Institute (CSIR), Chattar Manzil Palace, M.G. Road, Lucknow, 226001, Uttar Pradesh, India. Abstract The chemotherapy of visceral leishmaniasis (VL) has several limitations including resistance and toxicity of the existing drugs. Downregulation of immune system further aggravates the problems. To combat this situation, leishmanicidal efficacy of already marketed standard antifungal drug, fluconazole under the approach of "therapeutic switching" in combination with standard antileishmanial drug, miltefosine, and a potent immunomodulator agent, picroliv, were evaluated in hamsters infected with Leishmania donovani. Animals treated with fluconazole (50 mg/kg × 5 days, oral (p.o.)) + miltefosine (5 mg/kg × 5 days, p.o.) showed enhancement in antileishmanial efficacy (77%), reactive nitrogen species, reactive oxygen species, hydrogen peroxide, and phagocytosis index as compared to those treated with individual drugs. Addition of picroliv to this combination further increased the antileishmanial efficacy from 77% to 88%. Upregulation of cell-mediated immunity was also observed in animals of this group which strengthens the immunomodulatory role of picroliv. These findings suggest a new option for antileishmanial chemotherapy at lower cost and toxicity.
	PMID: 21212980 [PubMed - as supplied by publisher]
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3.	J Biol Chem. 2011 Jan 6. [Epub ahead of print] Antitumor quinol PMX464 is a cytocidal anti-trypanosomal inhibitor targeting trypanothione metabolism. Konig J, Wyllie S, Wells G, Stevens MF, Wyatt PG, Fairlamb AH. Bielefeld University, Germany; Abstract Better drugs are urgently needed for the treatment of African sleeping sickness. We tested a series of promising anticancer agents belonging to the 4-substituted 4-hydroxycyclohexa-2,5-dienones class ('quinols') and identified several with potent trypanocidal activity (EC50 < 100 nM). In mammalian cells, quinols are proposed to inhibit the thioredoxin / thioredoxin reductase system, which is absent from trypanosomes. Studies with the prototypical 4-benzothiazole-substituted quinol, PMX464, established that PMX464 is rapidly cytocidal, similar to the arsenical drug, melarsen oxide. Cell lysis by PMX464 was accelerated by addition of sub-lethal concentrations of glucose oxidase implicating oxidant defences in the mechanism of action. Whole cells treated with PMX464 showed a loss of trypanothione (T(SH)2), a unique dithiol in trypanosomes, and tryparedoxin peroxidase (TryP), a 2-Cys peroxiredoxin similar to mammalian thioredoxin peroxidase. Enzyme assays revealed that T(SH)2, TryP and another tryparedoxin-dependent peroxidase (TDPX) were inhibited in a time- and concentration-dependent manner. The inhibitory activities of various quinol analogues against these targets showed a good correlation with growth inhibition of T. brucei. The monothiols glutathione and L-cysteine bound in a 2:1 ratio with PMX464 with Kd values of 6 and 27 μM, respectively, whereas T(SH)2 bound more tightly in a 1:1 ratio with a Kd value of 430 nM. Overexpression of trypanothione synthetase in T. brucei decreased sensitivity to PMX464 indicating that the key metabolite T(SH)2 is a target for quinols. Thus, the quinol pharmacophore represents a novel lead structure for the development of a new drug against African sleeping sickness.
	PMID: 21212280 [PubMed - as supplied by publisher]
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4.	Am J Trop Med Hyg. 2011 Jan;84(1):109-117. A Species-Specific Approach to the Use of Non-Antimony Treatments for Cutaneous Leishmaniasis. Ramanathan R, Talaat KR, Fedorko DP, Mahanty S, Nash TE. Clinical Parasitology Unit and Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Center for Immunization Research, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland; Gastrointestinal Parasites Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Abstract Abstract. We used a species-specific approach to treat 10 patients with cutaneous leishmaniasis diagnosed using polymerase chain reaction. Non-antimony treatments (oral miltefosine, ketoconazole, and liposomal amphotericin B) were chosen as an alternative to pentavalent antimony drugs based on likely or proven drug efficacy against the infecting species. Leishmania Viannia panamensis was diagnosed in three patients and treated successfully with oral ketoconazole. Miltefosine treatment cured two patients with L. infantum chagasi. A wide variety of Leishmania responded to liposomal amphotericin B administered for 5-7 days. Three patients with L. V. braziliensis, one patient with L. tropica, and two patients with L. infantum chagasi were treated successfully. One person with L. V. braziliensis healed slowly because of a resistant bacterial superinfection, and a second patient with L. infantum chagasi relapsed and was retreated with miltefosine. These drugs were reasonably well-tolerated. In this limited case series, alternative non-antimony-based regimens were convenient, safe, and effective.
	PMID: 21212212 [PubMed - as supplied by publisher]
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5.	Am J Trop Med Hyg. 2011 Jan;84(1):107-8. Expansion of visceral leishmaniasis to the Western hilly part of Nepal. Pandey BD, Pun SB, Kaneko O, Pandey K, Hirayama K. Sukraraj Tropical and Infectious Diseases Hospital, Kathmandu, Nepal; Everest International Clinic and Research Center, Kathmandu, Nepal; Department of Protozoology, Institute of Tropical Medicine (NEKKEN) and the Global Center of Excellence Program, Nagasaki University, Nagasaki, Japan; Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and the Global Center of Excellence Program, Nagasaki University, Nagasaki, Japan. Abstract Abstract. We report the first case of visceral leishmaniasis (VL) from the non-endemic western hilly region of Nepal. The patient presented with a history of high-grade fever, abdominal distension, anemia, and weight loss. The case was confirmed as VL by microscopical detection of the Leishmania species amastigote in bone marrow aspiration and by a positive result for the rK39 test. The patient was treated with 0.5-1.0 mg/kg of Amphotericin B for 14 days (total of 405 mg), and amastigotes were negative on discharge. Five months later, this patient again developed fever, abdominal distension, and anemia. Clinical and hematological examinations suggested a relapse of VL. The patient was treated with 1 mg/kg of Amphotericin B for 18 days (total of 515 mg) and was clinically improved on discharge.
	PMID: 21212211 [PubMed - in process]
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6.	Am J Trop Med Hyg. 2011 Jan;84(1):102-106. Evaluation of Two rK39 Dipstick Tests, Direct Agglutination Test, and Indirect Fluorescent Antibody Test for Diagnosis of Visceral Leishmaniasis in a New Epidemic Site in Highland Ethiopia. Cañavate C, Herrero M, Nieto J, Cruz I, Chicharro C, Aparicio P, Mulugeta A, Argaw D, Blackstock AJ, Alvar J, Bern C. World Health Organization Collaborating Center for Leishmaniasis, National Center of Microbiology, and National Center of Tropical Medicine, Instituto de Salud Carlos III, Madrid, Spain; Disease Prevention and Control Programmes, World Health Organization, Addis Ababa, Ethiopia; Médecins Sans Frontières-Ethiopia, Operational Centre Barcelona-Athens, Addis Zemen, Ethiopia; Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia; Atlanta Research and Education Foundation, Decatur, Georgia; Department for the Control of Neglected Tropical Diseases, Leishmaniasis Control Program, World Health Organization, Geneva, Switzerland. Abstract Abstract. We assessed the performance characteristics of two rK39 immunochromatographic tests, a direct agglutination test (DAT), and an indirect immunofluorescent antibody test (IFAT) in the site of a new epidemic of visceral leishmaniasis (VL) in northwestern Ethiopia. The study population was composed of 179 patients with suspected VL and 67 controls. The sensitivities of Kalazar Detect(®), DiaMed-IT Leish(®), DAT, and IFAT in 35 polymerase chain reaction-confirmed VL cases were 94.3%, 91.4%, 91.4%, and 100%, respectively, and the specificities were 98.5%, 94%, 98.5%, and 98.5%, respectively. In a Bayesian latent class analysis of all 246 specimens, the estimated sensitivities were 90.5%, 89%, 88.8%, and 96% for Kalazar Detect(®), DiaMed-IT Leish(®), DAT, and IFAT, respectively; DAT showed the highest estimated specificity (97.4%). Both rK39 immunochromatographic tests perform as well as DAT, and are suitable for VL diagnosis in first-level health centers in this area of Ethiopia.
	PMID: 21212210 [PubMed - as supplied by publisher]
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7.	Am J Trop Med Hyg. 2011 Jan;84(1):91-98. Metabonomic Investigation of Single and Multiple Strain Trypanosoma brucei brucei Infections. Li JV, Saric J, Wang Y, Utzinger J, Holmes E, Balmer O. Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom; State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, People's Republic of China; Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut; Institute of Zoology, University of Basel, Basel, Switzerland. Abstract Abstract. Although co-infections are common and can have important epidemiologic and evolutionary consequences, studies exploring biochemical effects of multiple-strain infections remain scarce. We studied metabolic responses of NMRI mice to Trypanosoma brucei brucei single (STIB777AE-Green1 or STIB246BA-Red1) and co-infections using a (1)H nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling strategy. All T. b. brucei infections caused an alteration in urinary biochemical composition by day 4 postinfection, characterized by increased concentrations of 2-oxoisocaproate, D-3-hydroxybutyrate, lactate, 4-hydroxyphenylacetate, phenylpyruvate, and 4-hydroxyphenylpyruvate, and decreased levels of hippurate. Although there were no marked differences in metabolic signatures observed in the mouse infected with a single or dual strain of T. b. brucei, there was a slower metabolic response in mice infected with T. b. brucei green strain compared with mice infected with either the red strain or both strains concurrently. Pyruvate, phenylpyruvate, and hippurate were correlated with parasitemia, which might be useful in monitoring responses to therapeutic interventions.
	PMID: 21212208 [PubMed - as supplied by publisher]
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8.	Travel Med Infect Dis. 2011 Jan 4. [Epub ahead of print] Manifestations of paediatric Leishmania infantum infections in Malta. Pace D, Williams TN, Grochowska A, Betts A, Attard-Montalto S, Boffa MJ, Vella C. Paediatric Infectious Diseases Clinic, Mater Dei Hospital, Msida, Malta. Abstract Leishmania infantum is endemic in the Maltese archipelago, a group of islands in the Mediterranean which are visited frequently by tourists from Northern European countries. The burden of leishmaniasis is highest in children who may present with cutaneous or visceral manifestations. We describe systematically the manifestations, diagnosis and management of leishmaniasis in children <14 years of age, who had a histopathological diagnosis of leishmaniasis in Malta, from 2004 to 2008. Eleven children were diagnosed with leishmaniasis; 8 children (15-44 months of age) had visceral disease and three (aged 9-13 years) suffered cutaneous infections. Prolonged high grade fever, pallor, hepatosplenomegaly, and pancytopenia were common presenting features of visceralisation. Diagnosis was based on the visualisation of amastigotes from bone marrow aspirates. Pentavalent antimonials were associated with treatment failure in two children, whilst liposomal amphotericin B was curative in all. Children with cutaneous leishmaniasis had dry crusted ulcero-nodular lesions on exposed areas which responded to intra-lesional instillation of sodium stibogluconate or to cryotherapy. Leishmaniasis should be included in the differential diagnosis of fever and hepatosplenomegaly or chronic cutaneous lesions in children who travel to Malta. Copyright © 2010 Elsevier Ltd. All rights reserved.
	PMID: 21212024 [PubMed - as supplied by publisher]
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9.	Bioorg Med Chem Lett. 2010 Dec 10. [Epub ahead of print] Compounds containing 2-substituted imidazole ring for treatment against human African trypanosomiasis. Samant BS, Sukhthankar MG. Natural Product and Medicinal Chemistry (NPMC) research group, Division of Pharmaceutical chemistry, Faculty of Pharmacy, Rhodes University, Grahamstown 6140, South Africa. Abstract A series of compounds containing 2-substituted imidazoles has been synthesized from imidazole and tested for its biological activity against human African trypanosomiasis (HAT). The 2-substituted 5-nitroimidazoles such as fexinidazole (7a) and 1-[4-(1-methyl-5-nitro-1H-imidazol-2-ylmethoxy)-pyridin-2-yl-piperazine (9e) exhibited potent activity against T. brucei in vitro with low cytotoxicity and good solubility. The presence of the NO(2) group at the 5-position of the imidazole ring in 2-substituted imidazoles is the crucial factor to inhibit T. brucei. Copyright © 2010 Elsevier Ltd. All rights reserved.
	PMID: 21211967 [PubMed - as supplied by publisher]
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10.	Health Res Policy Syst. 2011 Jan 6;9(1):1. [Epub ahead of print] Social sciences research in neglected tropical diseases 2: A bibliographic analysis. Reidpath DD, Allotey P, Pokhrel S. Abstract ABSTRACT: BACKGROUND: There are strong arguments for social science and interdisciplinary research in the neglected tropical diseases. These diseases represent a rich and dynamic interplay between vector, host, and pathogen which occurs within social, physical and biological contexts. The overwhelming sense, however, is that neglected tropical diseases research is a biomedical endeavour largely excluding the social sciences. The purpose of this review is to provide a baseline for discussing the quantum and nature of the science that is being conducted, and the extent to which the social sciences are a part of that. METHODS: A bibliographic analysis was conducted of neglected tropical diseases related research papers published over the past 10 years in biomedical and social sciences. The analysis had textual and bibliometric facets, and focussed on chikungunya, dengue, visceral leishmaniasis, and onchocerciasis. RESULTS: There is substantial variation in the number of publications associated with each disease. The proportion of the research that is social science based appears remarkably consistent (<4%). A textual analysis, however, reveals a degree of misclassification by the abstracting service where a surprising proportion of the "social sciences" research was pure clinical research. Much of the social sciences research also tends to be "hand maiden" research focused on the implementation of biomedical solutions. CONCLUSION: There is little evidence that scientists pay any attention to the complex social, cultural, biological, and environmental dynamic involved in human pathogenesis. There is little investigator driven social science and a poor presence of interdisciplinary science. The research needs more sophisticated funders and priority setters who are not beguiled by uncritical biomedical promises.
	PMID: 21210997 [PubMed - as supplied by publisher]
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