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 11

1.	Med Parazitol (Mosk). 2011 Jul-Sep;(3):37-41. [The epidemiological features of visceral leishmaniasis, revealed on examination of children by polymerase chain reaction, in the Papsky District, Namangan Region, Uzbekistan]. [Article in Russian] [No authors listed] Abstract Patients with visceral leishmaniasis (VL) have been registered in the Papsky District, Namangan Region, Uzbekistan, over the past 23 years. A total of 95 patients were notified in 1987 to 2009. In 2007-2008, a mass survey using the polymerase chain reaction (PCR) within the international INTAS project 05-100006-8043 was conducted in 5 population aggregates of the Papsky District, Namangan Region, Uzbekistan, where VL cases had been regularly registered in the last years. Bone marrow and venous and peripheral blood smears were used as a test material. A total of 234 samples, including 3 bone marrow biopsy specimens, 9 venous blood samples and 222 peripheral blood ones, were tested. All the samples were on the glass slides. Three groups were identified among the examinees. Group 1 consisted of 13 subjects who had been ill at different times. Group 2 comprised 27 children treated at hospital for various diagnoses. Group 3 (the largest one, n=190) included apparently healthy children. All the children of this group felt well and had no symptoms of any illnesses at the examination. In this group, 85 (44.7%) subjects were PCR-positive. Twenty-four (55.8%) of 43 children in the age group of 0-3 years were PCR-positive; the 4-7-year age group comprised 66 subjects and 33 (50%) of them were PCR-positive. Group over 7 years of age included 81 subjects; 45 (55.5%) were PCR-positive. The results of the mass survey with PCR, which covered the 5 population aggregates in the Papsky District, Namangan Region, Uzbekistan, suggest the epidemic activity of a synathropic focus of VL and make us look at many fixed notions of its epidemiology in new contexts.
	PMID: 21936088 [PubMed - in process]

2.	Med Parazitol (Mosk). 2011 Jul-Sep;(3):32-7. [Human and canine visceral leishmaniasis in the Papsky District, Namangan Region, Uzbekistan: seroepidemiological and seroepizootological surveys]. [Article in Russian] [No authors listed] Abstract In 2007 - 2008, four (Chodak, Oltinkan, Gulistan, and Chorkesar) of 9 population aggregates in the Papsky District, Namangan Region, Uzbekistan, where visceral leishmaniasis (VL) cases had been registered in the last years were selected to make seroepidemiological and seroepizootological surveys within the international project funded by INTAS grant 05-100006-8043. The surveys of the populations were conducted visiting their homesteads. These additionally included children's and health care facilities where all children aged less than 14 years were examined. On examining the children, their peripheral blood (approximately 0.1 ml) was taken on filter paper for serological assays. Canine blood was sampled from the vein. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect antibodies to VL pathogens. A total of 521 children were examined for two years, by applying ELISA. Five hundred and fourteen blood samples from children younger than 14 years, 162 dogs, 4 foxes, and 1 cat were tested. Testing 514 children's blood samples for VL pathogen antigen ascertained that in the 4 population aggregates there was an average of 10% VL-seropositive children, including those who were ill with VL at the moment of the examination and had been ill. The highest number of VL-seropositive samples (14.9%) was found in the settlement of Chodak. VL pathogen antibodies were detected in 26 (61.9%) of 42 dogs with the clinical signs of VL. VL-positive tests were found in 26 (21.6%) of 120 apparently healthy dogs. The samples from 4 foxes and 1 cat were negative. Immunological findings indicated that 0-3-year-old children were a group that is most susceptible to VL in the study focus of this disease. The high proportion of dogs with VL may account for the rise in infant morbidity and suggests the epizootic strain in the focus of VL in the Papsky District.
	PMID: 21936087 [PubMed - in process]

3.	Pharm Res. 2011 Sep 21. [Epub ahead of print] Mitochondria and Trypanosomatids: Targets and Drugs. Fidalgo LM, Gille L. Source Departamento de Parasitología, Instituto de Medicina Tropical "Pedro Kourí", Apartado Postal No. 601, Marianao 13, Ciudad Habana, Cuba, monzote@ipk.sld.cu. Abstract The family Trypanosomatidae, flagellated parasitic protozoa, is responsible for important infectious diseases in humans: sleeping sickness, Chagas diseases and leishmaniasis. Currently, development of effective vaccines against these parasites remains an unrealized goal, and clinical management is based on chemotherapeutics. Cost, toxicity and resistance problems of conventional drugs result in an urgent need to identify and develop new therapeutic alternatives. The sound understanding of parasites, biology is key for identifying novel lead structures and new drug targets. This article reviews current knowledge about mitochondrial drug targets and existing drugs against Trypanosoma and Leishmania. In the past, several targets in trypanosomatid mitochondria (electron transport chain, kDNA and topoisomerases, tRNA import and fatty acid synthesis) have been identified. It has been suggested that inhibition of certain targets is involved in triggering apoptosis by impairment of mitochondrial membrane potential and/or production of reactive oxygen species. The inhibitory mechanism of approved drugs, such as pentamidine, nifurtimox, artemisinin and atovaquone, is described in parallel with others products from preclinical studies. In spite of the large amount of genetic information, the analysis of the phenotype of the trypanosomatid mitochondrion in different life stages will remain a useful tool to design new active compounds with selective toxicity against these parasites.
	PMID: 21935742 [PubMed - as supplied by publisher]

4.	PLoS One. 2011;6(9):e24141. Epub 2011 Sep 14. Arabinosylated Lipoarabinomannan Skews Th2 Phenotype towards Th1 during Leishmania Infection by Chromatin Modification: Involvement of MAPK Signaling. Bhattacharya P, Gupta G, Majumder S, Adhikari A, Banerjee S, Halder K, Bhattacharya Majumdar S, Ghosh M, Chaudhuri S, Roy S, Majumdar S. Source Division of Molecular Medicine, Bose Institute, Kolkata, India. Abstract The parasitic protozoan Leishmania donovani is the causative organism for visceral leishmaniasis (VL) which persists in the host macrophages by deactivating its signaling machinery resulting in a critical shift from proinflammatory (Th1) to an anti-inflammatory (Th2) response. The severity of this disease is mainly determined by the production of IL-12 and IL-10 which could be reversed by use of effective immunoprophylactics. In this study we have evaluated the potential of Arabinosylated Lipoarabinomannan (Ara-LAM), a cell wall glycolipid isolated from non pathogenic Mycobacterium smegmatis, in regulating the host effector response via effective regulation of mitogen-activated protein kinases (MAPK) signaling cascades in Leishmania donovani infected macrophages isolated from BALB/C mice. Ara-LAM, a Toll-like receptor 2 (TLR2) specific ligand, was found to activate p38 MAPK signaling along with subsequent abrogation of extracellular signal-regulated kinase (ERKs) signaling. The use of pharmacological inhibitors of p38MAPK and ERK signaling showed the importance of these signaling pathways in the regulation of IL-10 and IL-12 in Ara-LAM pretreated parasitized macrophages. Molecular characterization of this regulation of IL-10 and IL-12 was revealed by chromatin immunoprecipitation assay (CHIP) which showed that in Ara-LAM pretreated parasitized murine macrophages there was a significant induction of IL-12 by selective phosphorylation and acetylation of histone H3 residues at its promoter region. While, IL-10 production was attenuated by Ara-LAM pretreatment via abrogation of histone H3 phosphorylation and acetylation at its promoter region. This Ara-LAM mediated antagonistic regulations in the induction of IL-10 and IL-12 genes were further correlated to changes in the transcriptional regulators Signal transducer and activator of transcription 3 (STAT3) and Suppressor of cytokine signaling 3 (SOCS3). These results demonstrate the crucial role played by Ara-LAM in regulating the MAPK signaling pathway along with subsequent changes in host effector response during VL which might provide crucial clues in understanding the Ara-LAM mediated protection during Leishmania induced pathogenesis.
	PMID: 21935379 [PubMed - in process]

5.	J Leukoc Biol. 2011 Sep 20. [Epub ahead of print] Myeloid-derived suppressor cells help protective immunity to Leishmania major infection despite suppressed T cell responses. Pereira WF, Ribeiro-Gomes FL, Guillermo LV, Vellozo NS, Montalvão F, Dosreis GA, Lopes MF. Source *Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and. Abstract Th1/Th2 cytokines play a key role in immune responses to Leishmania major by controlling macrophage activation for NO production and parasite killing. MDSCs, including myeloid precursors and immature monocytes, produce NO and suppress T cell responses in tumor immunity. We hypothesized that NO-producing MDSCs could help immunity to L. major infection. Gr1(hi)(Ly6C(hi)) CD11b(hi) MDSCs elicited by L. major infection suppressed polyclonal and antigen-specific T cell proliferation. Moreover, L. major-induced MDSCs killed intracellular parasites in a NO-dependent manner and reduced parasite burden in vivo. By contrast, treatment with ATRA, which induces MDSCs to differentiate into macrophages, increased development of lesions, parasite load, and T cell proliferation in draining LNs. Altogether, these results indicate that NO-producing MDSCs help protective immunity to L. major infection, despite suppressed T cell proliferation.
	PMID: 21934068 [PubMed - as supplied by publisher]

6.	J Infect Dis. 2011 Sep 20. [Epub ahead of print] Miltefosine Effectively Modulates the Cytokine Milieu in Indian Post Kala-Azar Dermal Leishmaniasis. Mukhopadhyay D, Das NK, Roy S, Kundu S, Barbhuiya JN, Chatterjee M. Source Department of Pharmacology, Institute of Post Graduate Medical Education and Research. Abstract Background. The increasing incidence of unresponsiveness to antimonials in leishmaniasis prompted the use of newer drugs such as miltefosine. Miltefosine influences macrophage effector functions, but its effect on patients with post kala-azar dermal leishmaniasis (PKDL) has not been evaluated.Methodology. The immunomodulatory activity of miltefosine was evaluated in patients with PKDL by studying the expression of activation markers (CD14 and CD16) and costimulatory molecules (CD80 and CD86) on circulating monocytes, levels of pro-inflammatory cytokines (tumor necrosis factor α, interleukin 6, interleukin 1β, and interleukin 8) and anti-inflammatory cytokines (interleukin 10, transforming growth factor β, interleukin 4, and interleukin 13) in serum and peripheral blood mononuclear cell culture supernatants, and serum nitrite and arginase activity.Results. Miltefosine on circulating monocytes upregulated expression of CD16 and CD86 and reduced that of CD14. Miltefosine also induced a significant increase in circulating levels of pro-inflammatory cytokines with a concomitant decrease in anti-inflammatory cytokines. Its macrophage activating potential was evidenced by its ability to decrease serum arginase activity and increase serum nitrite.Conclusions. Miltefosine increased the proportion of monocytes that have a pro-inflammatory phenotype, which was accompanied by an enhanced secretion of pro-inflammatory cytokines and increased levels of serum nitrite. The decrease in anti-inflammatory cytokine levels and serum arginase activity collectively indicated that miltefosine triggered a robust T-helper 1 response that facilitated parasite elimination.
	PMID: 21933878 [PubMed - as supplied by publisher]

7.	Clin Microbiol Infect. 2011 Oct;17(10):1478-83. doi: 10.1111/j.1469-0691.2011.03630.x. Leishmaniasis chemotherapy-challenges and opportunities. Croft SL, Olliaro P. Source ) Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK ) UNICEF/UNDP/World Bank/WHO Special Programme for Research & Training in Tropical Diseases, Geneva, Switzerland CH ) Centre for Tropical Medicine and Vaccinology, Nuffield Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK. Abstract Clin Microbiol Infect 2011; 17: 1478-1483 ABSTRACT: Although there have been significant advances in the treatment of visceral leishmaniasis (VL), there remain challenges to ensure that treatments effective in India are also effective in other regions of the world and to identify treatment for post kala-azar dermal leishmaniasis as well as the opportunity to develop a safe oral short-course treatment. At the same time, there have been few advances for the treatment of simple or complex forms of cutaneous leishmaniasis (CL), other than topical paromomycin formulations. The main challenge for CL is to ensure that this disease is on the research and development agenda, so that new drugs are evaluated or compounds are screened in appropriate models, and that the standardization of quality of clinical trials is guaranteed. Problems also remain in the treatment of HIV/leishmaniasis co-infected patients. We are some way from having the ideal treatments for VL and CL and drug research and development for these diseases must remain focused. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.
	PMID: 21933306 [PubMed - in process]

8.	Clin Microbiol Infect. 2011 Oct;17(10):1471-7. doi: 10.1111/j.1469-0691.2011.03635.x. Leishmaniasis impact and treatment access. den Boer M, Argaw D, Jannin J, Alvar J. Source Leishmaniasis Control Programme, WHO/IDM. Av. Appia, Geneva, Switzerland. Abstract Clin Microbiol Infect 2011; 17: 1471-1477 ABSTRACT: According to disease burden estimates, leishmaniasis ranks third in disease burden in disability-adjusted life years caused by neglected tropical diseases and is the second cause of parasite-related deaths after malaria; but for a variety of reasons, it is not receiving the attention that would be justified seeing its importance. This is especially apparent in the unnecessarily and unacceptably poor access to timely and appropriate treatment for patients. To our knowledge, this is the first publication that addresses the major issues associated with poor access to drugs for leishmaniasis and that outlines a number of feasible and practical solutions. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.
	PMID: 21933305 [PubMed - in process]

9.	Clin Microbiol Infect. 2011 Oct;17(10):1451-1461. doi: 10.1111/j.1469-0691.2011.03640.x. Clinical pleiomorphism in human leishmaniases, with special mention of asymptomatic infection. Bañuls AL, Bastien P, Pomares C, Arevalo J, Fisa R, Hide M. Source  UMR MIVEGEC (IRD 224-CNRS 5290-Université Montpellier 1)  Université Montpellier 1 (UFR Médecine) and Centre Hospitalier Universitaire, Laboratoire de Parasitologie-Mycologie, National Reference Centre (CNR) for Leishmania, Montpellier  INSERM U895, C3M, Bâtiment Universitaire Archimed  Centre Hospitalier Universitaire de Nice, Laboratoire de Parasitologie-Mycologie, Nice, France  Instituto de Medicina Tropical 'Alexander von Humboldt' y Departamento de Bioquimica, Biolgia Molecular y Farmacologia, Universidad Peruana Cayetano Heredia, Lima, Peru  Laboratori de Parasitologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain. Abstract Clin Microbiol Infect 2011; 17: 1451-1461 ABSTRACT: This review gives an update of current knowledge on the clinical pleiomorphism of Leishmania, with a special emphasis on the case of asymptomatic carriage. The first part describes the numerous unusual expressions of the disease that occur besides the classic (visceral, cutaneous, and mucocutaneous) forms of leishmaniases. The second part deals with progress in the understanding of disease outcome in humans, and the possible future approaches to improve our knowledge in the field. The third part highlights the role of the too often neglected asymptomatic carrier compartment. This group could be key to understanding infraspecific differences in virulence and pathogenicity of the parasite, as well as identifying the genetic determinants involved in the expression of the disease. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.
	PMID: 21933304 [PubMed - as supplied by publisher]

10.	Clin Microbiol Infect. 2011 Oct;17(10):1449-50. doi: 10.1111/j.1469-0691.2011.03588.x. Leishmaniases control: what part for development and what part for research? Bastien P. Source Université Montpellier 1 (UFR Médecine) and Centre Hospitalier Universitaire, Laboratoire de Parasitologie-Mycologie, National Reference Centre (CNR) for Leishmania  UMR MIVEGEC (IRD 224-CNRS 5290-Université Montpellier 1), Montpellier, France E-mail: p-bastien@chu-montpellier.fr.
	PMID: 21933303 [PubMed - in process]