Thursday, May 27, 2010

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 12

1. Geospat Health. 2010 May;4(2):155-65.

Influence of topography on the endemicity of Kala-azar: a study based on remote sensing and geographical information system.

Bhunia GS, Kesari S, Jeyaram A, Kumar V, Das P.

Vector Biology and Control Division, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna 800 007, Bihar, India.

Abstract

Kala-azar, a fatal infectious disease in many Indian states, particularly in Bihar, West Bengal, Uttar Pradesh, and Jharkhand, is caused by the protozoan parasite Leishmania donovani and transmitted by the sandfly vector Phlebotomus argentipes. The vector is distributed all over the country but the disease is confined to particular zones since before the last century. In this study, parameters such as altitude, temperature, humidity, rainfall and the normalized difference vegetation index (NDVI) were investigated for correlation with the distribution of the disease in the northeastern corner of the Indian sub-continent. Data analysis on Kala-azar prevalence during the period 2005-2007 in the four states showed that the highest prevalence was below 150 m of altitude with very few cases located above the 300 m level. Low NDVI value ranges (0.03-0.015) correlated with a high occurrence of the disease. The maximum temperatures in the affected sites varied between an upper level of 25-29 degrees C and a minimum of 16-20 degrees C. The rainfall in these areas fluctuated between 1154 and 1834 mm. As the disease showed a high correlation with the prevailing topographic conditions, an attempt was made to improve the relative strength of the approach to predict the potential for endemicity of leishmaniasis by introducing satellite imagery complemented with a geographical information system database.

PMID: 20503185 [PubMed - in process]
2. Histol Histopathol. 2010 Jul;25(7):877-87.

Histopathological and parasitological investigations of ear healthy skin of dogs naturally and experimentally infected with Leishmania (Leishmania) chagasi.

Figueiredo MM, Moura EP, Costa MM, Ribeiro VM, Michalick MS, Tafuri WL, Tafuri WL.

Department of General Pathology, Federal University of Minas Gerais, Belo Horizonte, Brazil.

Abstract

Although 90% of clinical cases of American visceral leishmaniasis (AVL) occur in the northeastern region of Brazil, the incidence of cases in recent years has increased in southeastern states such as Minas Gerais (MG), where the disease has been reported in several cities, including Belo Horizonte, the state capital. Some studies have shown a strong correlation between the incidence of AVL and canine visceral leishmaniasis (CVL) in Belo Horizonte. A study of 108 dogs with parasite Leishmania chagasi detected by immuno-histochemistry in healthy ear skin was obtained from two distinct geographical areas: 55 from a metropolitan area of the municipality (Santa Luzia, MG) and 53 dogs from a central area of Belo Horizonte. In parallel, a group of 10 beagles were experimentally infected with L. chagasi. Considering the clinical aspects of all naturally infected dogs, symptomatic dogs were more frequent than asymptomatic ones, especially animals from the metropolitan area compared with the central area (79.6% and 20.3%, respectively). A chronic exudate was observed in the ear of 51 out of 55 dogs naturally infected from the metropolitan area (92.7%) and 45 out of 53 dogs naturally infected from the central area (84.9%). Importantly, asymptomatic dogs from the central area harbor more parasites in the skin than the asymptomatic ones from the metropolitan area. In addition, a profound difference was noted in the intensity of the inflammatory reaction and parasite load in the skin of experimental infected dogs.

PMID: 20503176 [PubMed - in process]
3. PLoS Pathog. 2010 May 20;6(5):e1000907.

Leishmania donovani Isolates with Antimony-Resistant but Not -Sensitive Phenotype Inhibit Sodium Antimony Gluconate-Induced Dendritic Cell Activation.

Haldar AK, Yadav V, Singhal E, Bisht KK, Singh A, Bhaumik S, Basu R, Sen P, Roy S.

Division of Infectious Diseases and Immunology, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata, India.

Abstract

The inability of sodium antimony gluconate (SAG)-unresponsive kala-azar patients to clear Leishmania donovani (LD) infection despite SAG therapy is partly due to an ill-defined immune-dysfunction. Since dendritic cells (DCs) typically initiate anti-leishmanial immunity, a role for DCs in aberrant LD clearance was investigated. Accordingly, regulation of SAG-induced activation of murine DCs following infection with LD isolates exhibiting two distinct phenotypes such as antimony-resistant (Sb(R)LD) and antimony-sensitive (Sb(S)LD) was compared in vitro. Unlike Sb(S)LD, infection of DCs with Sb(R)LD induced more IL-10 production and inhibited SAG-induced secretion of proinflammatory cytokines, up-regulation of co-stimulatory molecules and leishmanicidal effects. Sb(R)LD inhibited these effects of SAG by blocking activation of PI3K/AKT and NF-kappaB pathways. In contrast, Sb(S)LD failed to block activation of SAG (20 microg/ml)-induced PI3K/AKT pathway; which continued to stimulate NF-kappaB signaling, induce leishmanicidal effects and promote DC activation. Notably, prolonged incubation of DCs with Sb(S)LD also inhibited SAG (20 microg/ml)-induced activation of PI3K/AKT and NF-kappaB pathways and leishmanicidal effects, which was restored by increasing the dose of SAG to 40 microg/ml. In contrast, Sb(R)LD inhibited these SAG-induced events regardless of duration of DC exposure to Sb(R)LD or dose of SAG. Interestingly, the inhibitory effects of isogenic Sb(S)LD expressing ATP-binding cassette (ABC) transporter MRPA on SAG-induced leishmanicidal effects mimicked that of Sb(R)LD to some extent, although antimony resistance in clinical LD isolates is known to be multifactorial. Furthermore, NF-kappaB was found to transcriptionally regulate expression of murine gammaglutamylcysteine synthetase heavy-chain (mgammaGCS(hc)) gene, presumably an important regulator of antimony resistance. Importantly, Sb(R)LD but not Sb(S)LD blocked SAG-induced mgammaGCS expression in DCs by preventing NF-kappaB binding to the mgammaGCS(hc) promoter. Our findings demonstrate that Sb(R)LD but not Sb(S)LD prevents SAG-induced DC activation by suppressing a PI3K-dependent NF-kappaB pathway and provide the evidence for differential host-pathogen interaction mediated by Sb(R)LD and Sb(S)LD.

PMID: 20502630 [PubMed - in process]
4. PLoS One. 2010 May 18;5(5):e10697.

Trypsin-Like Serine Proteases in Lutzomyia longipalpis - Expression, Activity and Possible Modulation by Leishmania infantum chagasi.

Telleria EL, de Araújo AP, Secundino NF, d'Avila-Levy CM, Traub-Csekö YM.

Laboratório de Biologia Molecular de Parasitas e Vetores, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract

BACKGROUND: Midgut enzymatic activity is one of the obstacles that Leishmania must surpass to succeed in establishing infection. Trypsins are abundant digestive enzymes in most insects. We have previously described two trypsin cDNAs of L. longipalpis: one (Lltryp1) with a bloodmeal induced transcription pattern, the other (Lltryp2) with a constitutive transcription pattern. We have now characterized the expression and activity of trypsin-like proteases of Lutzomyia longipalpis, the main vector of visceral leishmaniasis in Brazil. METHODOLOGY AND PRINCIPAL FINDINGS: In order to study trypsin expression profiles we produced antibodies against peptides specific for Lltryp1 and Lltryp2. The anti-Lltryp1-peptide antibody revealed a band of 28 kDa between 6 and 48 hours. The anti-Lltryp2 peptide antibody did not evidence any band. When proteinaceous substrates (gelatin, hemoglobin, casein or albumin) were co-polymerized in polyacrylamide gels, insect midguts obtained at 12 hours after feeding showed a unique proteolytic pattern for each substrate. All activity bands were strongly inhibited by TLCK, benzamidine and 4-amino-benzamidine, indicating that they are trypsin-like proteases. The trypsin-like activity was also measured in vitro at different time points after ingestion of blood or blood containing Leishmania infantum chagasi, using the chromogenic substrate BArhoNA. L. longipalpis females fed on blood infected with L. i. chagasi had lower levels of trypsin activity after 12 and 48 hours than non-infected insects, suggesting that the parasite may have a role in this modulation. CONCLUSIONS AND SIGNIFICANCE: Trypsins are important and abundant digestive enzymes in L. longipalpis. Protein production and enzymatic activity followed previously identified gene expression of a blood modulated trypsin gene. A decrease of enzymatic activity upon the parasite infection, previously detected mostly in Old World vectors, was detected for the first time in the natural vector-parasite pair L. longipalpis-L. i. chagasi.

PMID: 20502532 [PubMed - in process]
5. J Cell Sci. 2010 May 25. [Epub ahead of print]

Trafficking activity of myosin XXI is required in assembly of Leishmania flagellum.

Katta SS, Tammana TV, Sahasrabuddhe AA, Bajpai VK, Gupta CM.

Abstract

Actin-based myosin motors have a pivotal role in intracellular trafficking in eukaryotic cells. The parasitic protozoan organism Leishmania expresses a novel class of myosin, myosin XXI (Myo21), which is preferentially localized at the proximal region of the flagellum. However, its function in this organism remains largely unknown. Here, we show that Myo21 interacts with actin, and its expression is dependent of the growth stage. We further reveal that depletion of Myo21 levels results in impairment of the flagellar assembly and intracellular trafficking. These defects are, however, reversed by episomal complementation. Additionally, it is shown that deletion of the Myo21 gene leads to generation of ploidy, suggesting an essential role of Myo21 in survival of Leishmania cells. Together, these results indicate that actin-dependent trafficking activity of Myo21 is essentially required during assembly of the Leishmania flagellum.

PMID: 20501700 [PubMed - as supplied by publisher]
6. Exp Parasitol. 2010 May 22. [Epub ahead of print]

Imaging of the host/parasite interplay in cutaneous leishmaniasis.

Millington OR, Myburgh E, Mottram JC, Alexander J.

Centre for Biophotonics, University of Strathclyde, Glasgow, G4 0NR; Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, G4 0NR.

Abstract

An understanding of host parasite interplay is essential for the development of therapeutics and vaccines. Immunoparasitologists have learned a great deal from 'conventional'in vitro and in vivo approaches, but recent developments in imaging technologies have provided us (immunologists and parasitologists) with the ability to ask new and exciting questions about the dynamic nature of the parasite-immune system interface. These studies are providing us with new insights into the mechanisms involved in the initiation of a Leishmania infection and the consequent induction and regulation of the immune response. Here we review some of the recent developments and discuss how these observations can be further developed to understand the immunology of cutaneous Leishmania infection in vivo. Copyright © 2010 Elsevier Inc. All rights reserved.

PMID: 20501336 [PubMed - as supplied by publisher]
7. Parasitology. 2010 May 26:1-8. [Epub ahead of print]

Isolation of Trypanosoma caninum in domestic dogs in Rio de Janeiro, Brazil.

DE S Pinto AG, Schubach TM, Figueiredo FB, Baptista C, Fagundes A, DA S Barros JH, DE Paula CC, Toma HK, Madeira MF.

Laboratório de Vigilância em Leishmanioses, Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.

Abstract

SUMMARYThe domestic dog's involvement with different members of the Trypanosomatidae family has been the focus of several studies due to this animal's close proximity to man. Recently this animal has been infected by a new Trypanosoma species (T. caninum), described in Rio de Janeiro and 19 similar isolates were later obtained. The objective of this study was to identify these isolates. All samples were isolated from intact skin cultures and analysed morphologically, by biochemical isoenzyme electrophoresis assays and by several molecular PCR assays. Additionally, anti-Leishmania sp. antibodies were assessed using the indirect Immunofluorescence Antibody Test (IFAT) in all animals. The methodologies employed to identify the isolates, including partial nucleotide sequences of 18S rRNA gene, indicated patterns identical to T. caninum and patterns different from the other species, including T. cruzi and T. rangeli samples. A phylogenetic tree constructed with the partial 18S ribosomal sequence shows that T. caninum is clustered with T. pestanai. Ten (52.6%) animals presented anti-Leishmania sp. antibodies with titres varying from 1:40 to 1:320. Thus, the hypothesis that this protozoan has disseminated among the dogs in Rio de Janeiro must be considered. The importance of a correct diagnosis in those animals and the possible consequences in the areas where visceral leishmaniasis is found are discussed here.

PMID: 20500920 [PubMed - as supplied by publisher]
8. Br J Dermatol. 2010 May 25. [Epub ahead of print]

Efficacy of short-duration (twice a week) intralesional sodium stibogluconate in treatment of cutaneous leishmaniasis in India.

Bumb RA, Mehta RD, Ghiya BC, Jakhar R, Prasad N, Soni P, Lezama-Davila C, Satoskar AR.

Department of Skin, STD and Leprosy, SP Medical College, Bikaner, Rajasthan, India.

Abstract

Abstract Background: Cutaneous leishmaniasis (CL) is caused by Leishmania major and Leishmania tropica in the old world. Our city Bikaner, the "Thar Desert", situated in the north-western geographical corner of India, happens to be an endemic pocket for CL caused by Leishmania tropica. Skin lesions of CL heal slowly causing disfiguring scars if remained untreated. Current recommended treatment for CL comprises systemic administration of sodium stibogluconate (SSG) for 2-3 weeks. Five to seven injections of SSG intralesionally has also been found to be effective. Objectives: To determine the efficacy of a short-duration, twice a week intra-lesional SSG treatment for cutaneous leishmaniasis. Methods: Two hundred and twenty patients with cutaneous leishmaniasis having 298 lesions were included in the present study. They were divided into group A and B (110 patients each). Patients were treated with 5-7 intra-lesional injections of SSG in doses of 50mg/cm2 of lesion either once (group-A) or twice (group -B) a week. Improvement was recorded at 6, 8, 10, 12, 16, 20 and 24 weeks and the rate of complete cure was compared. Results: Complete cure rate at 6, 8, and 10 weeks was higher (20%, 57% and 72% respectively) in Group B as compared to Group A (12%, 36% and 61% respectively). The difference in cure rates at these time points were statistically significant (p < 0.05). The complete cure rate at 24 weeks was similar in both groups (96.09% in Group B and 91.91% in Group A). The remaining 3.91% and 8.09% of patients in group B and A were "non- responders", respectively. No major side effects were observed in either group. In all cured cases, there were no relapses reported up to two years after treatment. Conclusions: A short-duration, twice-a-week intra-lesional SSG treatment for cutaneous leishmaniasis accelerates cure and is highly effective and well tolerated.

PMID: 20500797 [PubMed - as supplied by publisher]
9. Vet Ophthalmol. 2010 May;13(3):139-43.

Detection of Leishmania spp. and associated inflammation in ocular-associated smooth and striated muscles in dogs with patent leishmaniosis.

Naranjo C, Fondevila D, Leiva M, Roura X, Peña T.

Department of Pathobiological Sciences, School of Veterinary Medicine, 2015 Linden Drive, Madison, 53706 WI, USA.

Abstract

Abstract Objective Canine leishmaniosis is a disease characterized by the wide distribution of the parasite throughout the tissues of the host. The purpose of this study was to describe the presence of Leishmania spp. and associated inflammation in ocular-associated muscles of dogs with patent leishmaniosis. Procedures Smooth muscles (iris dilator muscle, iris sphincter muscle, ciliary muscle, Müller muscle, smooth muscle of the periorbita and smooth muscle of the nictitating membrane) and striated muscles (orbicularis oculi muscle, obliquus dorsalis muscle and dorsal rectus muscle) were evaluated. Routine staining with hematoxylin and eosin and immunohistochemistry to detect Leishmania spp. were performed on tissue sections. Results Granulomatous inflammation was seen surrounding muscular fibers and was composed mainly of macrophages with scattered lymphocytes and plasma cells. This infiltrate could be seen in 52/473 (10.99%) samples of smooth muscle and 36/142 (25.35%) samples of striated muscle. Parasites were detected in 43/473 (9.09%) samples of smooth muscle and in 28/142 (19.71%) samples of striated muscle. Conclusions To the authors' knowledge, this is the first report assessing the presence of Leishmania spp. and associated infiltrate in intraocular, extraocular and adnexal smooth and striated muscles. The inflammation present in those muscles could contribute to clinical signs already described, such as blepharitis, uveitis, and orbital cellulitis.

PMID: 20500712 [PubMed - in process]
10. Parasite Immunol. 2010 Jun;32(6):440-9.

Leishmania mexicana lipophosphoglycan differentially regulates PKCalpha-induced oxidative burst in macrophages of BALB/c and C57BL/6 mice.

Delgado-Domínguez J, González-Aguilar H, Aguirre-García M, Gutiérrez-Kobeh L, Berzunza-Cruz M, Ruiz-Remigio A, Robles-Flores M, Becker I.

Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Colonia Doctores, México D.F., México.

Abstract

Summary Leishmania are protozoan parasites that infect macrophages and their survival is partially achieved through inhibition of the cellular oxidative burst by parasite lipophosphoglycan (LPG). PKCalpha is the predominant PKC isoenzyme required for macrophage oxidative burst, yet it is not known if different susceptibility of BALB/c and C57BL/6 mice to Leishmania mexicana could be related to PKCalpha. We analysed the effect of L. mexicana promastigotes and parasite LPG on expression of PKCalpha and on its activity in macrophages of both mouse strains. Our data show that expression of the isoenzyme was not altered either by LPG or by L. mexicana promastigotes. Yet LPG exerted opposing effects on PKCalpha activity of macrophages between both strains: in susceptible BALB/c cells, it inhibited PKCalpha activity, whereas in the more resistant strain it augmented enzymatic activity 2.8 times. In addition, LPG inhibited oxidative burst only in susceptible BALB/c macrophages and the degree of inhibition correlated with parasite survival. Promastigotes also inhibited PKCalpha activity and oxidative burst in macrophages of BALB/c mice, whereas in C57BL/6, they enhanced PKCalpha activity and oxidative burst inhibition was less severe. Our data indicate that control of PKCalpha-induced oxidative burst by L. mexicana LPG relates with its success to infect murine macrophages.

PMID: 20500675 [PubMed - in process]

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