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Sent on Tuesday, 2011 Jul 05Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Bioorg Med Chem Lett. 2011 Jun 12. [Epub ahead of print]New salicylamide and sulfonamide derivatives of quinoxaline 1,4-di-N-oxide with antileishmanial and antimalarial activities.Barea C, Pabón A, Castillo D, Zimic M, Quiliano M, Galiano S, Pérez-Silanes S, Monge A, Deharo E, Aldana I.SourceUnidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en FarmacobiologÃa Aplicada (CIFA), University of Navarra, Pamplona, Spain. AbstractContinuing with our efforts to identify new active compounds against malaria and leishmaniasis, 14 new 3-amino-1,4-di-N-oxide quinoxaline-2-carbonitrile derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against Plasmodium falciparum Colombian FCR-3 strain and Leishmania amazonensis strain MHOM/BR/76/LTB-012A. Further computational studies were carried out in order to analyze graphic SAR and ADME properties. The results obtained indicate that compounds with one halogenous group substituted in position 6 and 7 provide an efficient approach for further development of antimalarial and antileishmanial agents. In addition, interesting ADME properties were found. Copyright © 2011 Elsevier Ltd. All rights reserved. |
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| 2. | Med Hypotheses. 2011 Jul 1. [Epub ahead of print]Role of leptin in human visceral leishmaniasis?Dayakar A, Chandrasekaran S, Veronica J, Maurya R.SourceDepartment of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, Andhra Pradesh, India. AbstractHuman visceral leishmaniasis (VL) is frequently found in poor population who are suffering from malnutrition in endemic areas. Therefore, obviously they may have reduced levels of leptin due to reduction in number of adipocytes which are major source of leptin production. Human pathogenesis of VL and reduced levels of leptin both are associated with increase in Th2 type immune response, characterized by secretion of cytokines such as IL-4 and IL-10. Whereas, the protective immune response during visceral leishmaniasis is associated with effective Th1 type immune response characterized by secretion of IFN-γ, IL-2 and IL-12, which correlates with leptin induction of T cells polarizing to Th1 population and secretion of proinflammatory cytokines, and also inhibition of Th2 type response. Therefore, we hypothesized that leptin might be effective in treatment of visceral leishmaniasis alone or VL patients who have co-infection with other immune deficiency syndromes such as AIDS/diabetes/autoimmune disorders by regulation of Th1/Th2 homeostasis. Copyright © 2011 Elsevier Ltd. All rights reserved. |
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| 3. | Parasitol Int. 2011 Jun 24. [Epub ahead of print]Leishmanicidal activity of the Agaricus blazei Murill in different Leishmania species.Valadares DG, Duarte MC, Oliveira JS, Chávez-Fumagalli MA, Martins VT, Costa LE, Leite JP, Santoro MM, Régis WC, Tavares CA, Coelho EA.SourceDepartamento de BioquÃmica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. AbstractLeishmaniasis is a major public health problem, and the alarming spread of parasite resistance underlines the importance of discovering new therapeutic products. The present study aims to investigate the in vitro leishmanicidal activity of an Agaricus blazei Murill mushroom extract as compared to different Leishmania species and stages. A water extract proved to be effective against promastigotes and amastigotes-like stages of Leishmania amazonensis, L. chagasi, and L. major, with IC(50) values of 67.5, 65.8, and 56.8μg/mL for promastigotes, and 115.4, 112.3, and 108.4μg/mL for amastigotes-like stages, respectively. The infectivity of the three Leishmania species before and after treatment with the water extract was analyzed, and it could be observed that 82%, 57%, and 73% of the macrophages were infected with L. amazonensis, L. major, and L. chagasi, respectively. However, when parasites were pre-incubated with the water extract, and later used to infect macrophages, they were able to infect only 12.7%, 24.5%, and 19.7% of the macrophages, presenting reductions in the percentage of infections in the order of 44.1%, 30.1%, and 45.2% for L. amazonensis, L. chagasi, and L. major, respectively. In other experiments, macrophages that were infected with L. amazonensis, L. chagasi, or L. major, and later treated with the aforementioned extract, presented reductions of 84.4%, 79.6%, and 85.3% in the parasite burden after treatment. A confocal microscopy revealed the loss of the viability of the parasites within the infected macrophages after treatment with the water extract. The applied extract presented a low cytotoxicity in murine macrophages and a low hemolytic activity in type O(+) human red blood cells. No nitric oxide (NO) production, nor inducible nitric oxide syntase expression, could be observed in macrophages after stimulation with the water extract, suggesting that biological activity may be due to direct mechanisms other than macrophage activation by means of NO production. In conclusion, the results demonstrate that the A. blazei Murill water extract can potentially be used as a therapeutic alternative on its own, or in association with other drugs, to treat visceral and cutaneous leishmaniasis. Copyright © 2011 Elsevier B.V. All rights reserved. |
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| 4. | Trans R Soc Trop Med Hyg. 2011 Jun 30. [Epub ahead of print]Reappraisal of the immunopathogenesis of disseminated leishmaniasis: in situ and systemic immune response.Machado PR, Rosa ME, Costa D, Mignac M, Silva JS, Schriefer A, Teixeira MM, Bacellar O, Carvalho EM.SourceServiço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil. AbstractDisseminated leishmaniasis (DL) is an emerging form of Leishmania braziliensis infection characterised by multiple cutaneous lesions on different parts of the body and a high rate of mucosal involvement. Systemic production of TNFα and IFNγ in DL patients is lower than in cutaneous leishmaniasis (CL) caused by L. braziliensis, which may account for parasite dissemination due to the decreased ability to control parasite growth. In this study, the systemic and in situ immune response of DL and CL patients was characterised through evaluation of chemokine and cytokine production. In situ evaluation showed similar production of IFNγ, TNFα, IL-10, transforming growth factor-beta (TGFβ), chemokine (C-C motif) ligand 2 (CCL2), CCL3, CCL11 and chemokine (C-X-C motif) ligand 10 (CXCL10) in papular and ulcerative lesions from DL as well as in ulcerated lesions from CL. Serum levels of CXCL9, a chemokine that attracts T-cells, was higher in serum from DL than from CL. These data indicate that a decrease in the type 1 immune response in peripheral blood of DL patients is due to attraction of Leishmania antigen-activated T-cells to the multiple cutaneous lesions. This may account for the absence of or few parasites in the lesions and for the development of ulcers similar to those observed in CL. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. |
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| 5. | Microbes Infect. 2011 Jun 29. [Epub ahead of print]The effects of macrophage source on the mechanism of phagocytosis and intracellular survival of Leishmania.Christine Hsiao CH, Ueno N, Shao JQ, Schroeder KR, Moore KC, Donelson JE, Wilson ME.SourceMolecular and Cellular Biology Program, University of Iowa, Iowa City, IA 52242, USA. AbstractLeishmania spp. protozoa are obligate intracellular parasites that replicate in macrophages during mammalian infection. Efficient phagocytosis and survival in macrophages are important determinants of parasite virulence. Macrophage lines differ dramatically in their ability to sustain intracellular Leishmania infantum chagasi (Lic). We report that the U937 monocytic cell line supported the intracellular replication and cell-to-cell spread of Lic during 72 h after parasite addition, whereas primary human monocyte-derived macrophages (MDMs) did not. Electron microscopy and live cell imaging illustrated that Lic promastigotes anchored to MDMs via their anterior ends and were engulfed through symmetrical pseudopods. In contrast, U937 cells bound Lic in diverse orientations, and extended membrane lamellae to reorient and internalize parasites through coiling phagocytosis. Lic associated tightly with the parasitophorous vacuole (PV) membrane in both cell types. PVs fused with LAMP-1-expressing compartments 24 h after phagocytosis by MDMs, whereas U937 cell PVs remained LAMP-1 negative. The expression of one phagocytic receptor (CR3) was higher in MDMs than U937 cells, leading us to speculate that parasite uptake proceeds through dissimilar pathways between these cells. We hypothesize that the mechanism of phagocytosis differs between primary versus immortalized human macrophage cells, with corresponding differences in the subsequent intracellular fate of the parasite. Copyright © 2011. Published by Elsevier SAS. |
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| 6. | Mol Biochem Parasitol. 2011 Jun 23. [Epub ahead of print]Oxidative stress protection of Trypanosomes requires selenophosphate synthase.Costa FC, Oliva MA, de Jesus TC, Schenkman S, Thiemann OH.SourceLaboratory of Protein Crystallography and Structural Biology, Physics Institute of São Carlos, University of São Paulo, Av. Trabalhador São-Carlense 400, PO Box 369, 13566-590 São Carlos, SP, Brazil. AbstractSelenoproteins are characterized by the incorporation of at least one amino acid selenocysteine (Sec-U) encoded by in-frame UGA stop codons. These proteins, as well as the components of the Sec synthesis pathway, are present in members of the bacteria, archaea and eukaryote domains. Although not a ubiquitous pathway in all organisms, it was also identified in several protozoa, including the Kinetoplastida. Genetic evidence has indicated that the pathway is non-essential to the survival of Trypanosoma growing in non-stressed conditions. By analyzing the effects of RNA interference of the Trypanosoma brucei selenophosphate synthetase SPS2, we found a requirement under sub-optimal growth conditions. The present work shows that SPS2 is involved in oxidative stress protection of the parasite and its absence severely hampers the parasite survival in the presence of an oxidizing environment that results in an apoptotic-like phenotype and cell death. Copyright © 2011 Elsevier B.V. All rights reserved. |
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| 7. | Rev Bras Parasitol Vet. 2011 Abr-Jun;20(2):165-167.Phlebotomine fauna (Diptera: Psychodidae: Phlebotominae) in a residential area and in a fragment of savanna vegetation in the municipality of Pontal do Araguaia, Mato Grosso, Brazil.Amaral AF, Varjão JR, Silva GB, Arrais-Silva WW.SourceInstituto de Ciências Biológicas e da Saúde,Universidade Federal de Mato Grosso - UFMT,Campus Universitário do Araguaia, Rod. MT 100, Km 3,5,CEP 78698-000, Pontal do Araguaia - MT, Brazil. arrais-silva@ufmt.br. AbstractIdentification of phlebotomine species in endemic areas is fundamental for analyzing the eco-epidemiological determinants of leishmaniasis. This study had the aim of investigating the phlebotomine fauna in an urban area and in a fragment of native savanna in the municipality of Pontal do Araguaia, State of Mato Grosso, Brazil, using CDC light traps. One hundred and twenty-three phlebotomine specimens belonging to seventeen different species were caught. Our results indicate synanthropic potential among vector species for leishmaniasis, such as the species Lutzomyia cruzi, L. sallesi and L. whitmani. The species L. cerradincola had never been recorded in this region, such that this is the first report of this species in the State of Mato Grosso. |
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| 8. | Rev Bras Parasitol Vet. 2011 Abr-Jun;20(2):111-114.Presence of antibodies against Toxoplasma gondii, Neospora caninum and Leishmania infantum in dogs from PiauÃLopes MG, Mendonça IL, Fortes KP, Amaku M, Pena HD, Gennari SM.SourceDepartamento de Medicina Veterinária Preventiva e Saúde Animal,Faculdade de Medicina Veterinária e Zootecnia,Universidade de São Paulo - USP, Av. Prof. Orlando M. de Paiva, 87,Cidade Universitária, CEP 05508-270, São Paulo - SP, Brazil. sgennari@usp.br. AbstractThis study aimed to evaluate the presence of antibodies against Neospora caninum, Toxoplasma gondii and Leishmania infantum in dogs attended at the Veterinary Hospital of the Federal University of PiauÃ, Northeastern Brazil, where there are no reports of the occurrence of N. caninum and T. gondii in dogs. Serum samples from 530 dogs of genders, different ages and breeds from the municipality of Teresina and nearby towns were analyzed using three indirect fluorescent antibody tests, each one targeting one of the three agents. The associations between the parasites and gender, breed and age of the dogs were assessed by the chi-square test (p > 0.05). The occurrence of antibodies to N. caninum, T. gondii and L. infantum was 3.2, 18.0 and 78.1%, respectively. Toxoplasma gondii was more frequently found in older dogs (p < 0.05) whereas L. infantum was more common in animals aged between 1 to 3 years (p < 0.05). In order to evaluate potential associations between the presence of anti-N. caninum and anti-T. gondii antibodies and Leishmania infection, 240 dogs were selected (120 positive and 120 negative for Leishmania spp.), based on serological and parasitological diagnoses. No association was found between Leishmania spp. and the coccidian parasites (p > 0.05). The results confirm the exposure of dogs to these parasites in the State of PiauÃ. |
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| 9. | Rev Bras Parasitol Vet. 2011 Abr-Jun;20(2):97-102.Presence of amastigotes in th e central nervous system of hamsters infected with Leishmania sp.Oliveira ED, Oshiro ET, Pinto RV, Castro BC, Daniel KB, Oliveira JM, Júnior MS, Guimarães EB, Silva JM, Dorval ME.SourceLaboratório de Parasitologia, Departamento de Patologia,Centro de Ciências Biológicas e da Saúde, Faculdade de Medicina,Universidade Federal de Mato Grosso do Sul - UFMS,CP 549, CEP 79070-900, Campo Grande - MS, Brazil. elisoli@pop.com.br. AbstractVisceral leishmaniasis (VL) is a severe chronic disease caused by Leishmania (Leishmania) infantum chagasi. Better knowledge on the effects caused by this disease can help develop adequate clinical management and treatment. Parasitological and immunohistochemical studies were performed golden hamsters Mesocricetus auratus infected with bone marrow from individuals with VL in the State of Mato Grosso do Sul, central-west Brazil. The effects of parasitism in the spleen, liver, kidneys, lungs, heart and brain of the animals were examined. Eighteen hamsters were inoculated intraperitoneally, and six healthy animals were used as negative controls. The animals were kept in the animal house and checked for clinical signs. Specimens of each organ were examined for the presence of amastigotes. Immunohistochemical technique was performed in all brain specimens and organs negative on the direct examination of parasites. Direct examination of amastigotes was positive in the spleen and liver of all infected animals; 33.3% showed the parasite in the kidneys and lungs, and 16.7% in the heart. Parasitic forms were seen in 83.3% (15/18) of the brain examined. Immunohistochemistry confirmed the results of the direct examination, except in two specimens of lung tissue and in the brain specimens. Other studies are needed to further clarify the effect of the parasite in the central nervous system. |
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| 10. | Clin Microbiol Infect. 2011 Apr 5. doi: 10.1111/j.1469-0691.2011.03540.x. [Epub ahead of print]Evaluation of rK28 antigen for serodiagnosis of visceral Leishmaniasis in India.Vaish M, Bhatia A, Reed SG, Chakravarty J, Sundar S.Source) Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India ) Infectious Disease Research Institute, Seattle, WA, USA. AbstractClin Microbiol Infect ABSTRACT: Antibody detection is a safely applied method at the wide scale in diagnosis of visceral Leishmaniasis (VL). In order to further advance serodiagnosis, the rK28 antigen has been recently introduced as a candidate for diagnosis of VL. We evaluated the sensitivity and specificity of the rK28 antigen in a micro-ELISA format in comparison to the rk39 antigen. The test was conducted on 252 parasitologically confirmed VL cases, 103 endemic healthy controls, 95 non-endemic healthy controls, 88 other infectious disease and 53 follow-up cases. Of 252 parasitologically confirmed VL cases, 251 cases were reported positive by rK28 antigen, yielding 99.6% sensitivity (95% CI, 0.97-0.99), which was similar to the sensitivity of rK39 ELISA (99.6%) (95% CI, 0.97-0.99). Specificity of the rK28 antigen in non-endemic and endemic healthy controls was 100% (95% CI 0.96-1) and 94.17% (95% CI, 0.88-0.97), respectively. In 88 different diseases, specificity was 95.45% (95% CI, 0.84-0.96). With the rK39 antigen, specificity of non-endemic and endemic controls and different diseases was 100% (95% CI 0.96-1), 92.23% (95% CI 0.85-0.96) and 96.59% (95% CI 0.90-0.98), respectively. Our results show that rK39 and rK28 antigens have similar sensitivity and specificity and rK28 can also be used as a serodiagnostic tool in the endemic population of Bihar. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases. |
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