Friday, June 15, 2012

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 - 4 of 4

1. Curr Opin Microbiol. 2012 Jun 11. [Epub ahead of print]

Backseat drivers: the hidden influence of microbial viruses on disease.

Hartley MA, Ronet C, Fasel N.

Source

Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, Epalinges 1066, Switzerland.

Abstract

Because viral replication depends on the vigour of its host, many viruses have evolved incentives of fitness to pay their keep. When the viral host is a human pathogen, these fitness factors can surface as virulence: creating a Russian doll of pathogenesis where pathogens within pathogens complicate the disease process. Microbial viruses can even be independently immunogenic, as we recently reported for leishmania-virus. Thus, the incidence of this 'hyperpathogenism' is becoming an important clinical consideration and by appreciating the microbial-virus as a backseat driver of human disease, we could exploit its presence as a diagnostic biomarker and molecular target for therapeutic intervention. Here we discuss the prevalence of clinically relevant hyperpathogenism as well as the environmental sanctuaries that breed it.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22694933 [PubMed - as supplied by publisher]
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2. Vet Parasitol. 2012 May 3. [Epub ahead of print]

Apoptosis, inflammatory response and parasite load in skin of Leishmania (Leishmania) chagasi naturally infected dogs: A histomorphometric analysis.

Verçosa BL, Melo MN, Puerto HL, Mendonça IL, Vasconcelos AC.

Source

Laboratory of Apoptosis, Department of General Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Abstract

The skin has an important role in infection by Leishmania chagasi. Apoptosis modulates the inflammatory response acting distinctively either on the progression or regression of the lesions. The parasites interact with multiple regulatory systems inducing apoptosis in host cells, during cell invasion, stabilization and multiplication of pathogens. In this context, the aim of this study was to evaluate cell death within the inflammatory infiltrates, and to correlate these results with parasite load and clinical features of dogs naturally infected with L. chagasi. Fragments of skin pinnas (8 symptomatic+8 asymptomatic+6 negative controls) were used to characterize and measure the inflammatory response, parasite load and apoptosis. Diagnosis of canine leishmaniasis was confirmed by the detection of anti-Leishmania antibodies by IFA and ELISA in serum, direct visualization of the parasite and culture in spleen, liver, pinna, bone marrow and lymph nodes, and PCR (pinna). Histomorphometry was performed with images obtained from 20 representative histological fields in a light microscope. Ultra-thin sections were mounted over a 300 mesh grids, contrasted with 2% uranyl acetate and lead citrate and examined under a Transmission Electronic Microscopy. Amastigotes were only found in the skin of symptomatic animals (31.94±18.81). The number of foci and cellularity of the inflammatory infiltrates in symptomatic dogs were higher than in other groups and in asymptomatics were higher than in controls (p<0.05; Tukey). The average area, perimeter and extreme diameters of the inflammatory infiltrates obtained in symptomatic dogs were higher than in controls (p<0.05; Tukey). The apoptotic index was higher in symptomatic than in other groups and there was no difference between asymptomatics and controls (p<0.05; Tukey). Ultrastructurally, apoptotic cells were shrunken, with condensed nuclear chromatin and cytoplasm. Condensed nuclei were frequently fragmented. Internucleosomal DNA fragmentation occurred only in symptomatic cases. Amastigotes were observed within neutrophils and macrophages. Apoptosis is directly related to parasite load, intensity of inflammatory response and clinical manifestations in L. chagasi naturally infected dogs.

Copyright © 2012 Elsevier B.V. All rights reserved.

PMID: 22694833 [PubMed - as supplied by publisher]
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3. Vet Parasitol. 2012 May 23. [Epub ahead of print]

Comparative serum biochemical changes in mongrel dogs following single and mixed infections of Trypanosoma congolense and Trypanosoma brucei brucei.

Ezeokonkwo RC, Ezeh IO, Onunkwo JI, Onyenwe IW, Iheagwam CN, Agu WE.

Source

Department of Veterinary Parasitology and Entomology, University of Nigeria, Nsukka, Nigeria.

Abstract

The serum activities of alkaline phosphatase (AP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the serum levels of conjugated bilirubin (CB), blood urea nitrogen (BUN) and creatinine were studied following single and mixed infections of mongrel dogs with Trypanosoma congolense and Trypanosoma brucei brucei. Twenty mongrel dogs of both sexes aged between 3 and 6 months, and weighing between 2.5 and 5.9kg were used for the study. The dogs were kept in clean metal cages in a fly-proof house and were fed and given water ad libitum. The twenty dogs were divided into four groups of five dogs each. Group I dogs were uninfected control, group II were infected with T. congolense, group III were infected with T. brucei brucei and group IV were infected with both T. congolense and T. brucei brucei. Each dog in the infected groups II and III was inoculated intraperitonealy (i/p) with 1.0ml of PBS diluted blood containing 1.0×10(6) trypanosomes whereas each infected dog in group IV (mixed infection) was inoculated with 0.5ml of the PBS diluted blood containing 0.5×10(6)T. congolense and 0.5ml of the PBS diluted blood containing 0.5×10(6)T. brucei brucei i/p. Parasites were detectable in the blood of the infected dogs in groups II, III, and IV 10-13 days post infection (PI) with the mean pre-patent period (PP) of 12, 10, and 11 days respectively. Trypanosome infection caused a significant (P<0.05) increase in the serum activities of AP, ALT, AST and the serum levels of creatinine, CB, and BUN. The significant increases in the serum levels of CB, BUN, and creatinine and serum activities of AP and AST became noticeable from day seven PI in all the infected groups whereas that of ALT became noticeable from day 14 PI and increased continuously until the experiment was terminated. These increases however did not differ significantly (P>0.05) between the infected groups in most cases. It was thus concluded that single or mixed infection of mongrel dogs with T. congolense and T. brucei brucei resulted in significant increases in the serum activities of AP, AST, ALT and serum levels of creatinine, CB and BUN which in most cases did not differ significantly (P>0.05) among the infected groups.

Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

PMID: 22694831 [PubMed - as supplied by publisher]
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4. J Biomol Struct Dyn. 2012 Jun 12. [Epub ahead of print]

Mechanistic insights into the dual inhibition strategy for checking Leishmaniasis.

Grover A, Katiyar SP, Jeyakanthan J, Dubey VK, Sundar D.

Source

a Department of Biochemical Engineering and Biotechnology , Indian Institute of Technology (IIT) Delhi , Hauz Khas , New Delhi , 110016 , India.

Abstract

Leishmaniasis (1) is an endemic disease mainly caused by the protozoan Leishmania donovani (Ld). Polyamines have been identified as essential organic compounds for the growth and survival of Ld. These are synthesized in Ld by polyamine synthesis pathway comprising of many enzymes such as ornithine decarboxylase (ODC), spermidine synthase (SS), and S-adenosylmethionine decarboxylase. Inhibition of these enzymes in Ld offers a viable prospect to check its growth and development. In the present work, we used computational approaches to search natural inhibitors against ODC and SS enzymes. We predicted three-dimensional structures of ODC and SS using comparative modeling and molecular dynamics (MD) simulations. Thousands of natural compounds were virtually screened against target proteins using high throughput approach. MD simulations were then performed to examine molecular interactions between the screened compounds and functional residues of the active sites of the enzymes. Herein, we report two natural compounds of dual inhibitory nature active against the two crucial enzymes of polyamine pathway of Ld. These dual inhibitors have the potential to evolve as lead molecules in the development of antileishmanial drugs. (1)These authors contributed equally.

PMID: 22694167 [PubMed - as supplied by publisher]
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