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Sent on Thursday, 2011 Jun 23Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Handb Exp Pharmacol. 2011;(204):487-510.Therapeutic potential of phosphodiesterase inhibitors in parasitic diseases.Shakur Y, de Koning HP, Ke H, Kambayashi J, Seebeck T.SourceOtsuka Maryland Medicinal Laboratories Inc, 9900 Medical Center Drive, Rockville, MD, 20850, USA, yasminshakur@ymail.co. AbstractProtozoan parasites of the order kinetoplastida are the causative agents of three of the world's most important neglected human diseases: African trypanosomiasis, American trypanosomiasis, and leishmaniasis. Current therapies are limited, with some treatments having serious and sometimes lethal side effects. The growing number of cases that are refractory to treatment is also of concern. With few new drugs in development, there is an unmet medical need for new, more effective, and safer medications. Recent studies employing genetic and pharmacological techniques have begun to shed light on the role of the cyclic nucleotide phosphodiesterases in the life cycle of these pathogens and suggest that these important regulators of cyclic nucleotide signaling may be promising new targets for the treatment of parasitic diseases. |
| 2. | PLoS Negl Trop Dis. 2011 Jun;5(6):e1181. Epub 2011 Jun 14.Experimental Transmission of Leishmania infantum by Two Major Vectors: A Comparison between a Viscerotropic and a Dermotropic Strai n.Maia C, Seblova V, Sadlova J, Votypka J, Volf P.SourceDepartment of Parasitology, Faculty of Sciences, Charles University, Prague, Czech Republic. AbstractWe quantified Leishmania infantum parasites transmitted by natural vectors for the first time. Both L. infantum strains studied, dermotropic CUK3 and viscerotropic IMT373, developed well in Phlebotomus perniciosus and Lutzomyia longipalpis. They produced heavy late-stage infection and colonized the stomodeal valve, which is a prerequisite for successful transmission. Infected sand fly females, and especially those that transmit parasites, feed significantly longer on the host (1.5-1.8 times) than non-transmitting females. Quantitative PCR revealed that P. perniciosus harboured more CUK3 strain parasites, while in L. longipalpis the intensity of infection was higher for the IMT373 strain. However, in both sand fly species the parasite load transmitted was higher for the strain with dermal tropism (CUK3). All but one sand fly female infected by the IMT373 strain transmitted less than 600 promastigotes; in contrast, 29% of L. longipalpis and 14% of P. perniciosus infected with the CUK3 strain transmitted more than 1000 parasites. The parasite number transmitted by individual sand flies ranged from 4 up to 4.19×10(4) promastigotes; thus, the maximal natural dose found was still about 250 times lower than the experimental challenge dose used in previous studies. This finding emphasizes the importance of determining the natural infective dose for the development of an accurate experimental model useful for the evaluation of new drugs and vaccines. |
| 3. | PLoS Negl Trop Dis. 2011 Jun;5(6):e1189. Epub 2011 Jun 14.Identification of Peptide Mimotopes of Trypanosoma brucei gambiense Variant Surface Glycoproteins.Van Nieuwenhove LC, Rogé S, Balharbi F, Dieltjens T, Laurent T, Guisez Y, Büscher P, Lejon V.SourceDepartment of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium. AbstractBACKGROUND:The current antibody detection tests for the diagnosis of gambiense human African trypanosomiasis (HAT) are based on native variant surface glycoproteins (VSGs) of Trypanosoma brucei (T.b.) gambiense. These native VSGs are difficult to produce, and contain non-specific epitopes that may cause cross-reactions. We aimed to identify mimotopic peptides for epitopes of T.b. gambiense VSGs that, when produced synthetically, can replace the native proteins in antibody detection tests. METHODOLOGY/PRINCIPAL FINDINGS:PhD.-12 and PhD.-C7C phage display peptide libraries were screened with mouse monoclonal antibodies against the predominant VSGs LiTat 1.3 and LiTat 1.5 of T.b. gambiense. Thirty seven different peptide sequences corresponding to a linear LiTat 1.5 VSG epitope and 17 sequences corresponding to a discontinuous LiTat 1.3 VSG epitope were identified. Seventeen of 22 synthetic peptides inhibited the binding of their homologous monoclonal to VSG LiTat 1.5 or LiTat 1.3. Binding of these monoclonal antibodies to respectively six and three synthetic mimotopic peptides of LiTat 1.5 and LiTat 1.3 was significantly inhibited by HAT sera (p<0.05). CONCLUSIONS/SIGNIFICANCE:We successfully identified peptides that mimic epitopes on the native trypanosomal VSGs LiTat 1.5 and LiTat 1.3. These mimotopes might have potential for the diagnosis of human African trypanosomiasis but require further evaluation and testing with a large panel of HAT positive and negative sera. |
| 4. | PLoS Negl Trop Dis. 2011 Jun;5(6):e1204. Epub 2011 Jun 14.TLR1/2 Activation during Heterologous Prime-Boost Vaccination (DNA-MVA) Enhances CD8+ T Cell Responses Providing Protection against Leishmania (Viannia).Jayakumar A, Castilho TM, Park E, Goldsmith-Pestana K, Blackwell JM, McMahon-Pratt D.SourceYale University School of Public Health, New Haven, Connecticut, United States of America. AbstractBACKGROUND:Leishmania (Viannia) parasites present particular challenges, as human and murine immune responses to infection are distinct from other Leishmania species, indicating a unique interaction with the host. Further, vaccination studies utilizing small animal models indicate that modalities and antigens that prevent infection by other Leishmania species are generally not protective. METHODOLOGY:Using a newly developed mouse model of chronic L. (Viannia) panamensis infection and the heterologous DNA prime - modified vaccinia virus Ankara (MVA) boost vaccination modality, we examined whether the conserved vaccine candidate antigen tryparedoxin peroxidase (TRYP) could provide protection against infection/disease. RESULTS:Heterologous prime - boost (DNA/MVA) vaccination utilizing TRYP antigen can provide protection against disease caused by L. (V.) panamensis. However, protection is dependent on modulating the innate immune response using the TLR1/2 agonist Pam3CSK4 during DNA priming. Prime-boost vaccination using DNA alone fails to protect. Prior to infection protectively vaccinated mice exhibit augmented CD4 and CD8 IFNγ and memory responses as well as decreased IL-10 and IL-13 responses. IL-13 and IL-10 have been shown to be independently critical for disease in this model. CD8 T cells have an essential role in mediating host defense, as CD8 depletion reversed protection in the vaccinated mice; vaccinated mice depleted of CD4 T cells remained protected. Hence, vaccine-induced protection is dependent upon TLR1/2 activation instructing the generation of antigen specific CD8 cells and restricting IL-13 and IL-10 responses. CONCLUSIONS:Given the general effectiveness of prime-boost vaccination, the recalcitrance of Leishmania (Viannia) to vaccine approaches effective against other species of Leishmania is again evident. However, prime-boost vaccination modality can with modulation induce protective responses, indicating that the delivery system is critical. Moreover, these results suggest that CD8 T cells should be targeted for the development of a vaccine against infection caused by Leishmania (Viannia) parasites. Further, TLR1/2 modulation may be useful in vaccines where CD8 T cell responses are critical. |
| 5. | Nucleic Acids Res. 2011 Jun 21. [Epub ahead of print]Intrachromosomal tandem duplication and repeat expansion during attempts to inactivate the subtelomeric essential gene GSH1 in Leishmania.Mukherjee A, Langston LD, Ouellette M.SourceCentre de Recherche en Infectiologie and Département de Microbiologie, Immunologie and Infectiologie, Université Laval, Québec, Canada, G1V 4G2 and Laboratory of DNA Replication, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, 10065, USA. AbstractGamma-glutamylcysteine synthetase encoded by GSH1 is the rate-limiting enzyme in the biosynthesis of glutathione and trypanothione in Leishmania. Attempts to generate GSH1 null mutants by gene disruption failed in Leishmania infantum. Removal of even a single allele invariably led to the generation of an extra copy of GSH1, maintaining two intact wild-type alleles. In the second and even third round of inactivation, the markers integrated at the homologous locus but always preserved two intact copies of GSH1. We probed into the mechanism of GSH1 duplication. GSH1 is subtelomeric on chromosome 18 and Southern blot analysis indicated that a 10-kb fragment flanked by 466-bp direct repeated sequences was duplicated in tandem on the same chromosomal allele each time GSH1 was targeted. Polymerase chain reaction analysis and sequencing confirmed the generation of novel junctions created at the level of the 466-bp repeats consequent to locus duplication. In loss of heterozygosity attempts, the same repeated sequences were utilized for generating extrachromosomal circular amplicons. Our results are consistent with break-induced replication as a mechanism for the generation of this regional polyploidy to compensate for the inactivation of an essential gene. This chromosomal repeat expansion through repeated sequences could be implicated in locus duplication in Leishmania. |
| 6. | Trop Med Int Health. 2011 Jun 21. doi: 10.1111/j.1365-3156.2011.02816.x. [Epub ahead of print]Endemic and opportunistic infections in Braz ilian solid organ transplant recipients.Batista MV, Pierrotti LC, Abdala E, Clemente WT, Girão ES, Rosa DR, Ianhez LE, Bonazzi PR, Lima AS, Fernandes PF, Pádua-Neto MV, Bacchella T, Oliveira AP, Viana CF, Ferreira MS, Shikanai-Yasuda MA.SourceInfections in Immunocompromised Host Group, Hospital das Clínicas da Faculdade de Medicina, University of São Paulo, São Paulo, Brazil Laboratory of Immunology, Hospital das Clínicas da Faculdade de Medicina, University of São Paulo, São Paulo, Brazil Liver Transplantation Division, Hospital das Clínicas da Faculdade de Medicina, University of São Paulo, São Paulo, Brazil Alfa Gastroenterology Institute, Hospital das Clínicas da Faculdade de Medicina, University of Minas Gerais, Minas Gerais, Brazil Renal Transplantation Unit, Hospital Universitário Walter Cantídio, University of Ceará, Ceará, Brazil Renal Transplant Unit, Infectious Diseases Department, Hospital das Clínicas da Faculdade de Medicina, University of Uberlândia, Minas Gerais, Brazil Renal Transplant Unit, Urological Division, Hospital das Clínicas da Faculdade de Medicina, University of São Paulo, São Paulo, Brazil. AbstractObjective To evaluate the frequency and clinical features of endemic and other opportunistic infections in liver or kidney transplant recipients in four transplant centres in different geographical areas of Brazil. Methods Retrospective analysis of medical and laboratory records of four transplant centres on endemic and other opportunistic infections in liver or kidney transplant recipients. Analyses were performed with spss statistical software. Results From 2001 to 2006, 1046 kidney and 708 liver transplants were registered in all centres. The average age was 42 years. Among 82 (4.7%) cases with infections, the most frequent was tuberculosis (2.0%), followed by systemic protozoal infections (0.7%), toxoplasmosis (0.4%) and visceral leishmaniasis (0.3%). Systemic fungal infections occurred in 0.6%, of which 0.4% were cryptococcosis and 0.2% were histoplasmosis. Dengue was the only systemic viral infection and was registered in two cases (0.1%), of which one was classified as the classic form and the other as dengue haemorrhagic fever. Nocardiosis was described in one case (0.05%). The infectious agents most frequently associated with diarrhoea were Blastocystis sp., Schistosoma mansoni and Strongyloides stercoralis. Conclusions Opportunistic Infections in transplant patients have a wide spectrum and may vary from asymptomatic to severe infections with high mortality. A better understanding of the epidemiology of endemic pathogens and clinical manifestations can contribute to the establishment of an early diagnosis as well as correct treatment aimed at decreasing morbidity and mortality. © 2011 Blackwell Publishing Ltd. |
| 7. | Expert Rev Anti Infect Ther. 2011 Jun;9(6):623-5.Radio frequency-induced heat therapy as first-line treatment for cutaneous leishmaniasis.Bumb RA, Satoskar AR.SourceDepartment of Dermatology, PBM Hospital and Sardar Patel Medical College, Bikaner, Rajasthan, India. |
| 8. | Rev Med Suisse. 2011 May 11;7(294):991-2, 994.[Indications for PCR in travel medicine]. [Article in French] Chappuis F.SourceService de médecine internationale et humanitaire, Département de médecine communautaire, de premier recours et des urgences HUG, 1211 Genève 14. francois.chappuis@hcuge.ch AbstractThe use of PCR-based molecular diagnosis in travel medicine remains limited to specific indications such as clinical suspicion of some of the viral hemorrhagic fevers (e.g. Ebola, Marburg), differential diagnosis between Entamoeba histolytica (pathogen) and E. dispar (non pathogen) in the stools, and parasitological diagnosis of cutaneous leishmaniasis. The scope of indications is likely to expand in the coming years with the development of techniques (e.g. multiplex PCR) able to identify several pathogens from a single sample. Simplification and cost-reduction of molecular techniques, which would allow for more equitable access to these diagnostic tools in countries where the targeted diseases are highly prevalent, pose major technological and ethical challenges. |
| 9. | Biol Chem. 2011 Apr;392(4):337-46. Epub 2011 Feb 9.Role of unique basic residues in cytotoxic, antibacterial and antiparasitic activities of human eosinophil cationic protein.Singh A, Batra JK.SourceImmunochemistry Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India. AbstractEosinophil granule proteins, eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin are members of the RNase A superfamily, which play a crucial role in host defense against various pathogens as they are endowed with several biological activities. Some of the biological activities possessed by ECP have been attributed to its strong basic character. In the current study, we have investigated the role of five unique basic residues, Arg22, Arg34, Arg61, Arg77 and His64 of ECP in its catalytic, cytotoxic, antibacterial and antiparasitic activities. These residues were changed to alanine to generate single and double mutants. None of the selected residues was found to be involved in the RNase activity of ECP. The substitution of all five residues individually was detrimental for the cytotoxic, antibacterial and antiparasitic activities of ECP; however, mutation of Arg22 and Arg34 resulted in the most significant effects. The double mutants also had reduced biological activities. All ECP mutants that had significantly reduced toxicity also had reduced membrane destabilization activity. Our study demonstrates that Arg22, Arg34, Arg61, Arg77 and His64 of ECP are crucial for its membrane destabilization activity, which appears to be the underlying mechanism of its cytotoxic, antibacterial and antiparasitic activities. |
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