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Sent on Saturday, 2010 Nov 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. | Parasitol Res. 2010 Nov 12. [Epub ahead of print]Characterization of Leishmania spp. causing cutaneous leishmaniasis in Manaus, Amazonas, Brazil.Camara Coelho LI, Paes M, Guerra JA, Barbosa MD, Coelho C, Lima B, Brito ME, Brandão Filho SP.Gerencia de Leishmanioses, Funbdação de Medicina Tropical do Amazonas, Manaus, Brazil, liarccoelho@yahoo.com.br. AbstractIn the State of Amazonas, American tegumentary leishmaniasis is endemic and presents a wide spectrum of clinical variability due to the large diversity of circulating species in the region. Isolates from patients in Manaus and its metropolitan region were characterized using monoclonal antibodies and isoenzymes belonging to four species of the parasite: Leishmania (Viannia) guyanensis, 73% (153/209); Leishmania (Viannia) braziliensis, 14% (30/209); Leishmania (Leishmania) amazonensis, 8% (17/209); and Leishmania (Viannia) naiffii, 4% (9/209). The most prevalent species was L. (V.) guyanensis. The principal finding of this study was the important quantity of infections involving more than one parasite species, representing 14% (29/209) of the total. The findings obtained in this work regarding the parasite are further highlighted by the fact that these isolates were obtained from clinical samples collected from single lesions. |
| PMID: 21072540 [PubMed - as supplied by publisher] | |
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| 2. | Rev Peru Med Exp Salud Publica. 2010 Mar;27(1):22-30.[Association between cutaneous leishmaniasis incidence and the human development index and its components in four endemic states of Venezuela.][Article in Spanish] Rodríguez-Morales AJ, Pascual-González Y, Benítez JA, López-Zambrano MA, Harter-Griep R, Vilca-Yengle LM, Cárdenas R.Sección de Inmunoparasitología, Instituto de Medicina Tropical Felix Pifano, Universidad Central de Venezuela, Caracas, Venezuela. AbstractObjectives. Assess potential relationships between the Human Development Index (HDI) and its components and the incidence of cutaneous leishmaniasis (CL) in four endemic States of Venezuela (Mérida, Trujillo, Lara and Sucre) in the period 1994-2003. Material and methods. Socioeconomical data (classified according the World Bank) was obtained from the National Institute of Statistics, and the epidemiological data from the Ministry of Health, both from Venezuela. For this ecological study the annual variation of the variables was assessed and also regression models were done. Results. The HDI varied in the period from 0.6746 in 1994 to 0.8144 in 2003 (p=0.90). During this time an increase in the cumulative incidence of Leishmaniasis was observed, particularly from 1998 (7.3 cases/100,000 pop) to 1999 (11.3 cases/100,000 pop). Analyzing the linear regression models, it was observed that the relationship between epidemiological and social variables was different at States levels. For Mérida and Trujillo it was observed a significant decrease in the CL regard to the increase of literacy (p<0.05), of the gross combined enrollment (p<0.05), life expectancy (p<0.05), money income (p<0.05) and the HDI (p<0.05). Conclusion. This information reflects the significant influence of socioeconomical indicators on the CL incidence at Trujillo and Merida, being an inverse relationship between both types of variables; with an increase or improvement in the socioeconomical indicators, the disease incidence rate decreased. |
| PMID: 21072446 [PubMed - as supplied by publisher] | |
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| 3. | PLoS Negl Trop Dis. 2010 Nov 2;4(11):e877.Risk factors for death in children with visceral leishmaniasis.de Queiroz Sampaio MJ, Cavalcanti NV, Alves JG, Fernandes Filho MJ, Correia JB.Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Brazil. AbstractBACKGROUND: Despite the major public health importance of visceral leishmaniasis (VL) in Latin America, well-designed studies to inform diagnosis, treatment and control interventions are scarce. Few observational studies address prognostic assessment in patients with VL. This study aimed to identify risk factors for death in children aged less than 15 years admitted for VL treatment in a referral center in northeast Brazil. METHODOLOGY/PRINCIPAL FINDINGS: In a retrospective cohort, we reviewed 546 records of patients younger than 15 years admitted with the diagnosis of VL at the Instituto de Medicina Integral Professor Fernando Figueira between May 1996 and June 2006. Age ranged from 4 months to 13.7 years, and 275 (50%) were male. There were 57 deaths, with a case-fatality rate of 10%. In multivariate logistic regression, the independent predictors of risk of dying from VL were (adjusted OR, 95% CI): mucosal bleeding (4.1, 1.3-13.4), jaundice (4.4, 1.7-11.2), dyspnea (2.8, 1.2-6.1), suspected or confirmed bacterial infections (2.7, 1.2-6.1), neutrophil count <500/mm(3) (3.1, 1.4-6.9) and platelet count <50,000/mm(3) (11.7, 5.4-25.1). A prognostic score was proposed and had satisfactory sensitivity (88.7%) and specificity (78.5%). CONCLUSIONS/SIGNIFICANCE: Prognostic and severity markers can be useful to inform clinical decisions such as whether a child with VL can be safely treated in the local healthcare facility or would potentially benefit from transfer to referral centers where advanced life support facilities are available. High risk patients may benefit from interventions such as early use of extended-spectrum antibiotics or transfusion of blood products. These baseline risk-based supportive interventions should be assessed in clinical trials. |
| PMID: 21072238 [PubMed - in process] | |
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| 4. | PLoS Negl Trop Dis. 2010 Nov 2;4(11):e873.Lutzomyia longipalpis Saliva Triggers Lipid Body Formation and Prostaglandin E(2) Production in Murine Macrophages.Araújo-Santos T, Prates DB, Andrade BB, Nascimento DO, Clarêncio J, Entringer PF, Carneiro AB, Silva-Neto MA, Miranda JC, Brodskyn CI, Barral A, Bozza PT, Borges VM.Centro de Pesquisas Gonçalo Moniz, FIOCRUZ-BA, Salvador, Brasil. AbstractBACKGROUND: Sand fly saliva contains molecules that modify the host's hemostasis and immune responses. Nevertheless, the role played by this saliva in the induction of key elements of inflammatory responses, such as lipid bodies (LB, also known as lipid droplets) and eicosanoids, has been poorly investigated. LBs are cytoplasmic organelles involved in arachidonic acid metabolism that form eicosanoids in response to inflammatory stimuli. In this study, we assessed the role of salivary gland sonicate (SGS) from Lutzomyia (L.) longipalpis, a Leishmania infantum chagasi vector, in the induction of LBs and eicosanoid production by macrophages in vitro and ex vivo. METHODOLOGY/PRINCIPAL FINDINGS: Different doses of L. longipalpis SGS were injected into peritoneal cavities of C57BL/6 mice. SGS induced increased macrophage and neutrophil recruitment into the peritoneal cavity at different time points. Sand fly saliva enhanced PGE(2) and LTB(4) production by harvested peritoneal leukocytes after ex vivo stimulation with a calcium ionophore. At three and six hours post-injection, L. longipalpis SGS induced more intense LB staining in macrophages, but not in neutrophils, compared with mice injected with saline. Moreover, macrophages harvested by peritoneal lavage and stimulated with SGS in vitro presented a dose- and time-dependent increase in LB numbers, which was correlated with increased PGE(2) production. Furthermore, COX-2 and PGE-synthase co-localized within the LBs induced by L. longipalpis saliva. PGE(2) production by macrophages induced by SGS was abrogated by treatment with NS-398, a COX-2 inhibitor. Strikingly, SGS triggered ERK-1/2 and PKC-α phosphorylation, and blockage of the ERK-1/2 and PKC-α pathways inhibited the SGS effect on PGE(2) production by macrophages. CONCLUSION: In sum, our results show that L. longipalpis saliva induces lipid body formation and PGE(2) production by macrophages ex vivo and in vitro via the ERK-1/2 and PKC-α signaling pathways. This study provides new insights regarding the pharmacological mechanisms whereby L. longipalpis saliva influences the early steps of the host's inflammatory response. |
| PMID: 21072234 [PubMed - in process] | |
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| 5. | PLoS Negl Trop Dis. 2010 Nov 2;4(11):e871.CD8 Cells of Patients with Diffuse Cutaneous Leishmaniasis Display Functional Exhaustion: The Latter Is Reversed, In Vitro, by TLR2 Agonists.Hernández-Ruiz J, Salaiza-Suazo N, Carrada G, Escoto S, Ruiz-Remigio A, Rosenstein Y, Zentella A, Becker I.Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México OD, México Distrito Federal, Mexico. AbstractLeishmania mexicana (Lm) causes localized (LCL) and diffuse (DCL) cutaneous leishmaniasis. DCL patients have a poor cellular immune response leading to chronicity. It has been proposed that CD8 T lymphocytes (CD8) play a crucial role in infection clearance, although the role of CD8 cytotoxicity in disease control has not been elucidated. Lesions of DCL patients have been shown to harbor low numbers of CD8, as compared to patients with LCL, and leishmanicidal treatment restores CD8 numbers. The marked response of CD8 towards Leishmania parasites led us to analyze possible functional differences between CD8 from patients with LCL and DCL. We compared IFNγ production, antigen-specific proliferation, and cytotoxicity of CD8 purified from PBMC against autologous macrophages (MO) infected with Leishmania mexicana (MOi). Additionally, we analyzed tissue biopsies from both groups of patients for evidence of cytotoxicity associated with apoptotic cells in the lesions. We found that CD8 cell of DCL patients exhibited low cytotoxicity, low antigen-specific proliferation and low IFNγ production when stimulated with MOi, as compared to LCL patients. Additionally, DCL patients had significantly less TUNEL(+) cells in their lesions. These characteristics are similar to cellular "exhaustion" described in chronic infections. We intended to restore the functional capacity of CD8 cells of DCL patients by preincubating them with TLR2 agonists: Lm lipophosphoglycan (LPG) or Pam3Cys. Cytotoxicity against MOi, antigen-specific proliferation and IFNγ production were restored with both stimuli, whereas PD-1 (a molecule associated with cellular exhaustion) expression, was reduced. Our work suggests that CD8 response is associated with control of Lm infection in LCL patients and that chronic infection in DCL patients leads to a state of CD8 functional exhaustion, which could facilitate disease spread. This is the first report that shows the presence of functionally exhausted CD8 T lymphocytes in DCL patients and, additionally, that pre-stimulation with TLR2 ligands can restore the effector mechanisms of CD8 T lymphocytes from DCL patients against Leishmania mexicana-infected macrophages. |
| PMID: 21072232 [PubMed - in process] | |
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| 6. | PLoS Negl Trop Dis. 2010 Nov 2;4(11):e868.Quantifying the burden of rhodesiense sleeping sickness in urambo district, Tanzania.Matemba LE, Fèvre EM, Kibona SN, Picozzi K, Cleaveland S, Shaw AP, Welburn SC.Tabora Research Centre, National Institute for Medical Research, Tabora, Tanzania. AbstractBACKGROUND: Human African trypanosomiasis is a severely neglected vector-borne disease that is always fatal if untreated. In Tanzania it is highly focalised and of major socio-economic and public health importance in affected communities. OBJECTIVES: This study aimed to estimate the public health burden of rhodesiense HAT in terms of DALYs and financial costs in a highly disease endemic area of Tanzania using hospital records. MATERIALS AND METHODS: Data was obtained from 143 patients admitted in 2004 for treatment for HAT at Kaliua Health Centre, Urambo District. The direct medical and other indirect costs incurred by individual patients and by the health services were calculated. DALYs were estimated using methods recommended by the Global Burden of Disease Project as well as those used in previous rhodesiense HAT estimates assuming HAT under reporting of 45%, a figure specific for Tanzania. RESULTS: The DALY estimate for HAT in Urambo District with and without age-weighting were 215.7 (95% CI: 155.3-287.5) and 281.6 (95% CI: 209.1-362.6) respectively. When 45% under-reporting was included, the results were 622.5 (95% CI: 155.3-1098.9) and 978.9 (95% CI: 201.1-1870.8) respectively. The costs of treating 143 patients in terms of admission costs, diagnosis, hospitalization and sleeping sickness drugs were estimated at US$ 15,514, of which patients themselves paid US$ 3,673 and the health services US$ 11,841. The burden in terms of indirect non-medical costs for the 143 patients was estimated at US$ 9,781. CONCLUSIONS: This study shows that HAT imposes a considerable burden on affected rural communities in Tanzania and stresses the urgent need for location- and disease-specific burden estimates tailored to particular rural settings in countries like Tanzania where a considerable number of infectious diseases are prevalent and, due to their focal nature, are often concentrated in certain locations where they impose an especially high burden. |
| PMID: 21072230 [PubMed - in process] | |
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| 7. | PLoS Negl Trop Dis. 2010 Nov 2;4(11):e865.LAMP for Human African Trypanosomiasis: A Comparative Study of Detection Formats.Wastling SL, Picozzi K, Kakembo AS, Welburn SC.Centre for Infectious Diseases, Division of Pathway Medicine, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, United Kingdom. AbstractLoop-mediated isothermal amplification (LAMP) is at the forefront of the search for innovative diagnostics for human African trypanosomiasis (HAT). Several simple endpoint detection methods have been developed for LAMP and here we compare four of these: (i) visualization of turbidity; (ii) addition of hydroxynaphthol blue before incubation; (iii) addition of calcein with MnCl(2) before incubation and (iv) addition of Quant-iT PicoGreen after incubation. These four methods were applied to four LAMP assays for the detection of human African trypanosomiasis, including two Trypanozoon specific and two Trypanosoma brucei rhodesiense specific reactions using DNA extracted from cryo-preserved procyclic form T. b. rhodesiense. A multi-observer study was performed to assess inter-observer reliability of two of these methods: hydroxynapthol blue and calcein with MnCl(2), using DNA prepared from blood samples stored on Whatman FTA cards. Results showed that hydroxynaphthol blue was the best of the compared methods for easy, inexpensive, accurate and reliable interpretation of LAMP assays for HAT. Hydroxynapthol blue generates a violet to sky blue colour change that was easy to see and was consistently interpreted by independent observers. Visible turbidity detection is not possible for all currently available HAT LAMP reactions; Quant-iT PicoGreen is expensive and addition of calcein with MnCl(2) adversely affects reaction sensitivity and was unpopular with several observers. |
| PMID: 21072228 [PubMed - in process] | |
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| 8. | Exp Parasitol. 2010 Nov 8. [Epub ahead of print]Leishmania donovani: Assessment of leishmanicidal effects of herbal extracts obtained from plants in the visceral leishmaniasis endemic area of Bihar, India.Singh SK, Bimal S, Narayan S, Jee C, Devla S, Das P, Bimal R.Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agamkuan, Patna-800007, India. AbstractOne obstacle faced in the effective control of visceral leishmaniasis (VL) is the limited number of available treatment options. Furthermore, control efforts have been hindered further by the emergence of Leishmania resistance to many of the available drugs. In this study, we investigated the anti-leishmanial properties of 30 medicinally important plants from the VL endemic area of Bihar, India and compared them to two available anti-leishmanial drugs (sodium antimony gluconate and amphotericin B) and two plant lectins (phytohemagglutinin and concanavalin A) on Leishmania donovani promastigotes in vitro at 24 and 48 h after initiation of culture. We identified 8 plant extracts in addition to phytohemagglutinin and amphotericin B that significantly inhibited the growth of promastigotes (p < 0.03). We further studied the minimum effective concentrations as well as the effect on axenic amastigotes viability and the cell cytotoxicity on human peripheral blood of 4 (Agave americana, Azadirachta indica, Eclipta alba and Piper longum) of the 8 plant extracts that induced significant promastigotes killing (p = 0.00098). Effect-based dose finding analysis revealed that the threshold concentration of A. americana required to eliminate L. donovani after 24 h was 0.05 mg/ml. A. indica and P. longum plant extracts eliminated L. donovani promastigotes after 48 h at concentrations of 0.1 and 0.5 mg/ml, respectively. E. alba eliminated the promastigotes at a concentration of 0.5 mg/ml within 24 h. The axenic amastigote killing response was 1.90-, 2.52- and 1.3-fold higher than the promastigote killing response with A. indica, A. americana and E. alba plant extracts, respectively. A. americana and A. indica, respectively, led to approximate 2.5- and 1.3-fold declines in mitochondrial dehydrogenase activity compared with control. E. alba stimulation resulted in an up-regulation of dehydrogenase activity (p = 0.00329). The CSA from P. longum was found to be least cytotoxic; the observed difference in mitochondrial activity was insignificant (p = 0.16314). Further studies may reveal the pharmacological significance of many of the plants with anti-leishmanial properties identified in the present study. Copyright © 2010. Published by Elsevier Inc. |
| PMID: 21070771 [PubMed - as supplied by publisher] | |
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| 9. | PLoS Negl Trop Dis. 2010 Aug 10;4(8). pii: e793.Tryp anosoma vivax infections: pushing ahead with mouse models for the study of Nagana. II. Immunobiological dysfunctions.Blom-Potar MC, Chamond N, Cosson A, Jouvion G, Droin-Bergère S, Huerre M, Minoprio P.Laboratoire d'Immunobiologie des Infections à Trypanosoma, Département d'Immunologie, Institut Pasteur, Paris, France. AbstractTrypanosoma vivax is the main species involved in trypanosomosis, but very little is known about the immunobiology of the infective process caused by this parasite. Recently we undertook to further characterize the main parasitological, haematological and pathological characteristics of mouse models of T. vivax infection and noted severe anemia and thrombocytopenia coincident with rising parasitemia. To gain more insight into the organism's immunobiology, we studied lymphocyte populations in central (bone marrow) and peripherical (spleen and blood) tissues following mouse infection with T. vivax and showed that the immune system apparatus is affected both quantitatively and qualitatively. More precisely, after an initial increase that primarily involves CD4(+) T cells and macrophages, the number of splenic B cells decreases in a step-wise manner. Our results show that while infection triggers the activation and proliferation of Hematopoietic Stem Cells, Granulocyte-Monocyte, Common Myeloid and Megacaryocyte Erythrocyte progenitors decrease in number in the course of the infection. An in-depth analysis of B-cell progenitors also indicated that maturation of pro-B into pre-B precursors seems to be compromised. This interferes with the mature B cell dynamics and renewal in the periphery. Altogether, our results show that T. vivax induces profound immunological alterations in myeloid and lymphoid progenitors which may prevent adequate control of T. vivax trypanosomosis. |
| PMID: 20711524 [PubMed - indexed for MEDLINE] | |
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| 10. | PLoS Negl Trop Dis. 2010 Aug 10;4(8):e797.Prophylactic efficacy of TcVac2 against Trypanosoma cruzi in mice.Gupta S, Garg NJ.Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America. AbstractBACKGROUND: Chagas disease is a major health problem in Latin America, and an emerging infectious disease in the US. Previously, we have screened the Trypanosoma cruzi sequence database by a computational/bioinformatics approach, and identified antigens that exhibited the characteristics of vaccine candidates. METHODOLOGY: We investigated the protective efficacy of a multi-component DNA-prime/protein-boost vaccine (TcVac2) constituted of the selected candidates and cytokine (IL-12 and GM-CSF) expression plasmids in a murine model. C57BL/6 mice were immunized with antigen-encoding plasmids plus cytokine adjuvants, followed by recombinant proteins; and two-weeks later, challenged with T. cruzi trypomastigotes. ELISA and flow cytometry were employed to measure humoral (antibody isotypes) and cellular (lymphocyte proliferation, CD4(+) and CD8(+) T cell phenotype and cytokines) responses. Myocardial pathology was evaluated by H&E and Masson's trichrome staining. PRINCIPAL FINDINGS: TcVac2 induced a strong antigen-specific antibody response (IgG2b>IgG1) and a moderate level of lymphocyte proliferation in mice. Upon challenge infection, TcVac2-vaccinated mice expanded the IgG2b/IgG1 antibodies and elicited a substantial CD8(+) T cell response associated with type 1 cytokines (IFN-gamma and TNF-alpha) that resulted in control of acute parasite burden. During chronic phase, antibody response persisted, splenic activation of CD8(+) T cells and IFN-gamma/TNF-alpha cytokines subsided, and IL-4/IL-10 cytokines became dominant in vaccinated mice. The tissue parasitism, inflammation, and fibrosis in heart and skeletal muscle of TcVac2-vaccinated chronic mice were undetectable by histological techniques. In comparison, mice injected with vector or cytokines only responded to T. cruzi by elicitation of a mixed (type 1/type 2) antibody, T cell and cytokine response, and exhibited persistent parasite burden and immunopathology in the myocardium. CONCLUSION: TcVac2-induced activation of type 1 antibody and lymphocyte responses provided resistance to acute T. cruzi infection, and consequently, prevented the evolution of chronic immunopathology associated with parasite persistence in chagasic hearts. |
| PMID: 20706586 [PubMed - indexed for MEDLINE] | |
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