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Sent on Tuesday, 2012 February 14Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| 1. | Exp Parasitol. 2012 Feb 1. [Epub ahead of print]The leishmanicidal flavonols quercetin and quercitrin target Leishmania (Leishmania) amazonensis arginase.da Silva ER, Maquiaveli CD, Magalhães PP.SourceDepartamento de Ciências Básicas, Universidade de São Paulo, Faculdade de Zootecnia e Engenharia de Alimentos, Av. Duque de Caxias Norte, 225, CEP 13635-900 Pirassununga, SP, Brazil. AbstractPolyamine biosynthesis enzymes are promising drug targets for the treatment of leishmaniasis, Chagas' disease and African sleeping sickness. Arginase, which is a metallohydrolase, is the first enzyme involved in polyamine biosynthesis and converts arginine into ornithine and urea. Ornithine is used in the polyamine pathway that is essential for cell proliferation and ROS detoxification by trypanothione. The flavonols quercetin and quercitrin have been described as antitrypanosomal and antileishmanial compounds, and their ability to inhibit arginase was tested in this work. We characterized the inhibition of recombinant arginase from Leishmania (Leishmania) amazonensis by quercetin, quercitrin and isoquercitrin. The IC(50) values for quercetin, quercitrin and isoquercitrin were estimated to be 3.8, 10 and 4.3μM, respectively. Quercetin is a mixed inhibitor, whereas quercitrin and isoquercitrin are uncompetitive inhibitors of L. (L.) amazonensis arginase. Quercetin interacts with the substrate l-arginine and the cofactor Mn(2+) at pH 9.6, whereas quercitrin and isoquercitrin do not interact with the enzyme's cofactor or substrate. Docking analysis of these flavonols suggests that the cathecol group of the three compounds interact with Asp129, which is involved in metal bridge formation for the cofactors Mn(A)(2+) and Mn(B)(2+) in the active site of arginase. These results help to elucidate the mechanism of action of leishmanicidal flavonols and offer new perspectives for drug design against Leishmania infection based on interactions between arginase and flavones. Copyright © 2012 Elsevier Inc. All rights reserved. |
| 2. | Int J Biol Macromol. 2012 Feb 3. [Epub ahead of print]Comparative modeling of HGPRT enzyme of L. donovani and binding affinities of different analogs of GMP.Ansari MY, Dikhit MR, Sahoo GC, Das P.SourceBioMedical Informatics Division, Rajendra Memorial Research Institute of Medical Sciences, Agam Kuan, Patna 800007, India; Pharmacoinformatics Dept., National Institute of Pharmaceutical Education and Research, Hajipur, India. AbstractHypoxanthine-guanine phosphoribosyl transferase (HGPRT; EC 2.4.2.8) is a central enzyme in the purine recycling pathway. Parasitic protozoa (Leishmania donovani) cannot synthesize purines de novo and utilize the salvage pathway to produce purine bases. Thus, this enzyme is targeted in drug discovery and development. The model of the monomeric L. donovani HGPRT showed that this enzyme is an α/β type protein with a PRTase type I folding pattern. Among all of the computationally screened compounds, pentamidine, 1,3-dinitroadamantane, acyclovir and analogs of acyclovir had higher binding affinities than the real substrate (guanosine monophosphate). Amino acids of HGPRT that are frequently involved in the binding of these compounds are Lys 66, Asp 74, Arg 77, Asp 81, Val 88, Tyr 182, Arg 192 and Arg 194. It is predicted that patients suffering from both HIV and visceral leishmaniasis (VL) may benefit if they are treated with acyclovir or pentamidine in conjunction with first-line antileishmanial therapies such as miltefosine and AmBisome. Copyright © 2012 Elsevier B.V. All rights reserved. |
| 3. | Phytomedicine. 2012 Feb 9. [Epub ahead of print]Anti-leishmanial activity of alkaloidal extracts obtained from different organs of Aspidosperma ramiflorum.Cunha AD, Chierrito TP, Machado GM, Leon LL, Silva CC, Tanaka JC, Souza LM, Gonçalves RA, Oliveira AJ.SourceDepartamento de Farmácia, Universidade Estadual de Maringá, Avenida Colombo, 5790, CEP 87.020-900, Maringá, PR, Brazil. AbstractThe present study was designated to evaluate semi-quantitative antileishmanial activity of alkaloidal extracts that were obtained from 1g of different parts of Aspidosperma ramiflorum (leaves, roots, seeds, and stem barks). Alkaloidal extracts of barks and leaves presented a good activity against the extracellular form (promastigotes) of Leishmania (L.) amazonensis. It is known that compounds responsible for the antileishmanial activity in the alkaloidal extracts from A. ramiflorum are the monoterpenoid indole alkaloids ramiflorine A and ramiflorine B, therefore extracts obtained from different plant parts were analyzed by electrospray ionization mass spectrometry (ESI-MS) in order to evidence the presence of these bioactive alkaloids. Based on these findings, alkaloidal extract from leaves was fractionated on preparative thin-layer chromatography in a bioassay-guided fractionation affording individual purified ramiflorines A and B. Both ramiflorines A and B showed significant activity against Leishmania (L.) amazonensis (LD(50) values of 18.5±6.5μg/ml and 12.63±5.52μg/ml, respectively). Our results are showing that alkaloidal extract from leaves is a promising alternative to the use of stem barks from A. ramiflorum. Copyright © 2011 Elsevier GmbH. All rights reserved. |
| 4. | Microbiol Res. 2012 Feb 9. [Epub ahead of print]Toll-like receptor signaling: A perspective to develop vaccine against leishmaniasis.Singh RK, Srivastava A, Singh N.SourceMolecular Immunology Laboratory, Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi 221 005, India. AbstractThe toll-like receptors (TLRs) are the sentinel factor of the innate immunity, which are essential for host defense. These receptors detect the presence of conserved molecular patterns of potentially pathogenic microorganisms and contribute in both, cellular as well as humoral immune responses. Leishmania is an intracellular pathogen that silently invades host immune system. After phagocytosis, it divides and proliferates in the harmful environment of host macrophages by down-regulating its vital effector functions. In leishmaniasis, the outcome of the infection basically relies on the skewed balance between Th1/Th2 immune responses. Lots of work have been done and on progress but still characterization of either preventive or prophylactic candidate antigen/s is far from satisfactory. How does Leishmania regulate host innate immune system? Still it is unanswered. TLRs play very important role during inflammatory process of various diseases such as cancer, bacterial and viral infections but TLR signaling is comparatively less explained in leishmanial infection. In the context to Th1/Th2 dichotomy, identification of leishmanial antigens that modulate toll-like receptor signaling will certainly help in the development of future vaccine. This review will initially describe global properties of TLRs, and later will discuss their role in the pathogenesis of leishmaniasis. Copyright © 2012 Elsevier GmbH. All rights reserved. |
| 5. | Pathol Biol (Paris). 2012 Feb 10. [Epub ahead of print]Usefulness of a PCR-based method in the detection and species identification of Leishmania from clinical samples.Chargui N, Haouas N, Jaouadi K, Gorcii M, Pratlong F, Dedet JP, Mezhoud H, Babba H.SourceUR 99/08-05, laboratoire de parasitologie-mycologie, département de biologie clinique B, faculté de pharmacie, 1, rue Avicenne, 5000 Monastir, Tunisia. AbstractThe aim of this study is to assess the usefulness of a simple, low-cost method for the detection and species identification of Leishmania isolated by in vitro culture or detected directly from clinical samples. A total of 110 samples were used in this study. Among these, 21 were human and canine peripheral bloods, 63 skin lesion material samples, eight reference strains and 18 Leishmania culture. Detection of Leishmania DNA with PCR using primers designed to amplify the internal transcribed spacer 1 (ITS1) region of the rRNA gene proved sufficiently sensitive at the level of 0.1 parasites per PCR reaction. Furthermore, followed by single-strand conformational polymorphism (SSCP), the PCR-ITS1 allowed the species identification of Leishmania. The inter-specific polymorphism of Leishmania was first validated on reference strains, and then this method was applied on clinical samples and culture. Typing identified all human and canine visceral leishmaniasis samples (21 samples) as L. infantum, 95.23% of the cutaneous leishmaniasis samples as L. major and 3.17% as L. killicki and 1.58% as L. infantum. A scheme of the PCR diagnosis procedure for the detection and identification of Leishmania parasites is proposed in this study. Copyright © 2012 Elsevier Masson SAS. All rights reserved. |
| 6. | Bioorg Med Chem Lett. 2012 Jan 28. [Epub ahead of print]Inhibitors of human histone deacetylase with potent activity against the African trypanosome Trypanosoma brucei.Kelly JM, Taylor MC, Horn D, Loza E, Kalvinsh I, Björkling F.SourceDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. AbstractA number of hydroxamic acid derivatives which inhibit human histone deacetylases were investigated for efficacy against cultured bloodstream form Trypanosoma brucei. Three out of the four classes tested displayed significant activity. The majority of compounds blocked parasite growth in the submicromolar range. The most potent was a member of the sulphonepiperazine series with an IC(50) of 34nM. These results identify lead compounds with potential for the development of a novel class of trypanocidal agent. Copyright © 2012 Elsevier Ltd. All rights reserved. |
| 7. | Ann Trop Med Parasitol. 2011 Dec;105(8):559-65.Diagnosis and identification of Leishmania spp. from Giemsa-stained slides, by real-time PCR and melting curve analysis in south-west of Iran.Khademvatan S, Neisi N, Maraghi S, Saki J.SourceAhvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. AbstractBACKGROUND:The aim of present study was describing a real-time PCR assay for the diagnosis and direct identification of Leishmania species on Giemsa-stained slides in south-west of Iran. MATERIALS AND METHODS:Altogether, 102 Giemsa-stained slides were collected from different part of south-west of Iran between 2008 and 2011. All the Giemsa-stained slides were examined under light microscope. After DNA extraction, real-time PCR amplification and detection were conducted with fluorescent SYBR Green I. For identification, PCR products were analysed with melting curve analysis. RESULTS:One hundred and two archived slides from suspected lesion examined by microscopy and real-time PCR. The sensitivity of the real-time PCR on Giemsa-stained slid was 98% (96/102). The melting curve analysis (T(m)) were 88·3±0·2°C for L. tropica (MHOM/IR/02/Mash10), 86·5±0·2°C for L. major (MHOM/IR/75/ER) and 89·4±0·3°C for L. infantum (MCAN/IR/97/LON 49), respectively. CONCLUSION:This study is first report in use of real-time PCR for diagnosis and identification of Leishmania spp. in Iran. Up to now, in Iran, the majority of identification of Leishmania species is restriction fragment length polymorphism (PCR-RFLP) of ITS1 and kinetoplast DNA. Our data showed that Giemsa-stained slides that were stored more than 3 years, can be use for Leishmania DNA extraction and amplification by real-time PCR. Compared to conventional PCR-based methods, the real-time PCR is extremely rapid with results and more samples can be processed at one time. |
| 8. | Ann Trop Med Parasitol. 2011 Dec;105(8):549-57.Beta-carboline-3-carboxamide derivatives as promising antileishmanial agents.Pedroso RB, Tonin LT, Ueda-Nakamura T, Filho BP, Sarragiotto MH, Nakamura CV.SourceUniversidade Estadual de Londrina, Rodovia Celso Garcia Cid, PR 445, Km 380, CEP 86051-990, Campus Universitário, Londrina, Paraná, Brazil. Abstract<title/> Leishmaniasis has an overwhelming impact on global public health especially in tropical and subtropical countries and the currently available antileishmanial drugs have serious side effects and low efficacy. Natural and synthetic compounds have been tested in the past few years against Leishmania and the beta-carboline class of compounds have shown great results in antiparasitic chemotherapy. In the present study, three 1-substituted beta-carboline-3-carboxamides (3-5) and 1-substituted beta-carboline-3-carboxylic acid (2) were synthesized and screened for in vitro activity against L. amazonensis. Compound 5 (N-benzyl 1-(4-methoxy)phenyl-9H-beta-carboline-3-carboxamide) had the best activity against promastigote and axenic amastigote forms with IC(50) of 2·6 and 1·0 μM, respectively. Its CC(50) on macrophages cell line was higher than 2457·0 μM with an SI ratio of 930·2. Against intracellular amastigote forms, it had a dose-dependent relationship with a 50% growth inhibitory concentration of 1·0 μM. Through morphological and ultrastructure analysis of promastigote forms treated with compound 5, alterations on cell shape and number of flagella and nuclear membrane damage were observed. For this, compound 5 supports the idea for more in vitro and in vivo studies. |
| 9. | Ann Dermatol Venereol. 2012 Feb;139(2):171-2. Epub 2011 Dec 5.[Sporotrichoid cutaneous leishmaniasis]. [Article in French] Er-Rami M, Lahlou H, Benjelloun S, Jakar A, Khalloufi A, El Haouri M.SourceService de parasitologie mycologie, hôpital militaire Moulay-Ismaïl, 50000 Meknès, Maroc. |
| 10. | Ann Pathol. 2012 Feb;32(1):40-52. Epub 2011 Mar 31.[Pathological peculiarities of chronic kidney disease in patient from sub-Saharan Africa. Review of data from the Democratic republic of Congo]. [Article in French] Pakasa NM, Sumaïli EK.SourceService d'anatomie pathologique, cliniques universitaires de Kinshasa, Université de Kinshasa, BP 864, Kinshasa XI, République démocratique du Congo (RDC). AbstractChronic kidney disease (CKD) is a major global public health problem. But kidney involvement is more common and appears more severe in Africa than in developed countries. The likely causes of end stage renal disease (ESRD) or CKD stage 3 and above in developed countries are diabetes, hypertension and less frequently glomerular diseases. In contrast, in decreasing order in Africa are glomerulopathies, hypertension and diabetes. The reasons for this preponderance of glomerular diseases are not fully known but may be linked to the persistence or reemergence of tropical diseases. This study reviews the kidney involvements more associated with common tropical diseases including HIV/AIDS. The most common HIV/AIDS lesion is a specific focal and segmental glomerulosclerosis (FSGS) termed HIV-associated nephropathy (HIV-AN). Renal complications of tropical parasites are heterogenous. Various glomerulopathies like FSGS occur during various filariasis infections. Schistosoma mansoni is responsible for membranoproliferative glomerulonephritis and amyloidosis. Human African trypanosomiasis is associated with cryoglobulinemic membranoproliferative glomerulonephritis. The Plasmodium malariae is mainly responsible for membranoproliferative glomerulonephritis. Acute patterns (acute tubular necrosis or acute postinfectious glomerulonephritis) are observed during Plasmodium falciparum infection. Several other viral, bacterial or mycobacterial infections like leprosy and tuberculosis still prevalent in Africa can also affect the kidney. Sickle cell disease is responsible for a variety of renal injuries. In conclusion, kidney lesions linked to tropical diseases partly explain the peculiar pattern of CKD of the black race and play a significant role in the current outbreak of the CKD in Subsaharan Africa. Copyright © 2011 Elsevier Masson SAS. All rights reserved. |
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