Wednesday, June 17, 2009

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 -5 of 5

1: J Med Microbiol. 2009 Jun 15. [Epub ahead of print]

A pro-apoptotic effect of Landrace of Piper betle- Bangla Mahoma on Leishmania donovani may be due to high content of eugenol.

Misra P, Kumar A, Khare P, Gupta S, Kumar N, Dube A.

1 Central Drug Research Institute;

In the absence of effective and safe treatment of Kala-azar (VL) - a most devastating parasitic disease caused by Leishmania donovani a need for the search of antileishmanial from natural resources, in common use, is imperative. Recently, a comparative in vitro antileishmanial activity of methanolic extract of two landraces of Piper betle- Bangla Mahoba (PB-BMM) and Kapoori Vellaikodi (PB-KVM) has been reported. Herein, the putative pathway responsible for death induced by the effective extract of PB-BMM in promastigotes as well as intracellular amastigotes form of L. donovani was assessed using various biochemical approaches. It was observed that PB-BM is capable of selectively inhibiting both the stages of Leishmania parasites by accelerating apoptotic events by generation of ROS targeting mitochondrion without any cytotoxicity to macrophages. Study was extended to reason out the presence/absence of activity in PB-BMM and PB-KVM on the basis of differences in essential oil composition present in methanolic extract assessed by gas chromatography and mass spectra. The essential oil from PB-BM was found to be rich in eugenol as compared to PB-KV. The antileishmanial efficacy of PB-BMM mediated through apoptosis is probably due to the higher content of eugenol in active landrace. This observation emphasizes the need of extending the studies related to traditional medicines from bioactive plants below species to gender/landrace level for better efficacy and reproducibility.

PMID: 19528177 [PubMed - as supplied by publisher]

2: Chem Phys Lipids. 2009 Jun 12. [Epub ahead of print]Click here to read

First total synthesis and antiprotozoal activity of (Z)-17-methyl-13-octadecenoic acid, a new marine fatty acid from the sponge Polymastia penicillus.

Carballeira NM, Montano N, Balaña-Fouce R, Prada CF.

Department of Chemistry, University of Puerto Rico, P.O. Box 23346, San Juan, Puerto Rico 00931-3346, USA.

The first total synthesis for the (Z)-17-methyl-13-octadecenoic acid was accomplished in seven steps and in a 45% overall yield. The use of (trimethylsilyl)acetylene was key in the synthesis. Based on a previous developed strategy in our laboratory the best synthetic route towards the title compound was first acetylide coupling of (trimethylsilyl)acetylene to the long-chain protected 12-bromo-1-dodecanol followed by a second acetylide coupling to the short-chain 3-methyl-1-bromobutane, which resulted in higher yields. Complete spectral data is also presented for the first time for this recently discovered fatty acid. The title compound displayed antiprotozoal activity against Leishmania donovani (EC(50) = 19.8mug/ml) and inhibited the leishmania DNA topoisomerase IB at concentrations of 50muM.

PMID: 19527698 [PubMed - as supplied by publisher]

3: Parasite Immunol. 2009 Jul;31(7):373-83.Click here to read

CTL responses to Leishmania mexicana gp63-cDNA vaccine in a murine model.

Ali SA, Rezvan H, McArdle SE, Khodadadi A, Asteal FA, Rees RC.

School of Science and Technology, Nottingham Trent University, Clifton, Nottingham, UK. selman.ali@ntu.ac.uk

Immunity to Leishmania is believed to be strongly dependent upon the activation of Th1 immune responses, although the exact role of cytotoxic T lymphocytes (CTLs) has not yet been determined. The aims of this study were to establish a suitable cytotoxicity assay to measure CTL activity and to compare immunity induced by Leishmania mexicana gp63 cDNA via i.m. injection and gene gun immunization in the BALB/c mouse model. The CTL activity was evaluated by short-term (51)Cr-release cytotoxicity assays against CT26 tumour cells transfected with L. mexicana gp63 cDNA and dendritic cells (DCs) loaded with soluble Leishmania antigen (SLA) as targets. The results clearly demonstrated that higher protection to L. mexicana infection was induced by gene gun DNA-immunization vs. i.m. injection. Cytotoxic T lymphocyte activity of splenocytes was observed in mice immunized either with L. mexicana gp63 cDNA or SLA and long-lived CTL activity was observed in immunized and/or re-challenged mice but not naïve mice infected with the parasite.

PMID: 19527453 [PubMed - in process]

4: Parasite Immunol. 2009 Jul;31(7):357-65.Click here to read

Secondary bacterial infection in plasma endotoxin levels and the acute-phase response of mice infected with Trypanosoma brucei brucei.

Ngure R, Burke J, Eckersall PD, Jennings FW, Mbai FN, Murray M.

Department of Biochemistry and Molecular Biology, Egerton University, Egerton Njoro, Kenya. ramuch68@yahoo.com

Murine Trypanosoma brucei brucei infection leads to elevated plasma endotoxin-like activity levels not related to parasitaemia levels accompanied by the development of acute-phase response and increased plasma levels of serum amyloid P (SAP) and haptoglobin (Hp). To determine the source of the endotoxin-like activity and role of secondary bacterial infection in the pathogenesis of trypanosomosis, infected mice were treated with the antibiotic ciprofloxacin. Plasma endotoxin-like activity levels, irrespective of treatment, were elevated three- to fourfold, beginning 7 days after infection. Plasma protein concentrations increased markedly following infection from 7 days after infection (DAI). Peak Hp and SAP concentrations in ciprofloxacin-treated and -untreated infected mice were attained 7 and 14 DAI, respectively. Thereafter, both protein levels gradually declined until the end of the experiment, but Hp levels for non-treated mice declined up to 21 DAI and thereafter significantly increased on 28 and 35 DAI. Whole-trypanosome lysate and the membrane-enriched fraction demonstrated endotoxin-like activity, with the former having higher levels. The results suggest that the endotoxin-like activity in trypanosome fractions and plasma of infected mice is due to the trypanosome. Further elevation of haptoglobin during the late stages of infection in non-treated mice suggests the involvement of secondary bacterial infection.

PMID: 19527451 [PubMed - in process]

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5: J Med Chem. 2009 Jun 15. [Epub ahead of print]Click here to read

One Scaffold, Three Binding Modes: Novel and Selective Pteridine Reductase 1 Inhibitors Derived from Fragment Hits Discovered by Virtual Screening.

Mpamhanga CP, Spinks D, Tulloch LB, Shanks EJ, Robinson DA, Collie IT, Fairlamb AH, Wyatt PG, Frearson JA, Hunter WN, Gilbert IH, Brenk R.

Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, U.K.

The enzyme pteridine reductase 1 (PTR1) is a potential target for new compounds to treat human African trypanosomiasis. A virtual screening campaign for fragments inhibiting PTR1 was carried out. Two novel chemical series were identified containing aminobenzothiazole and aminobenzimidazole scaffolds, respectively. One of the hits (2-amino-6-chloro-benzimidazole) was subjected to crystal structure analysis and a high resolution crystal structure in complex with PTR1 was obtained, confirming the predicted binding mode. However, the crystal structures of two analogues (2-amino-benzimidazole and 1-(3,4-dichloro-benzyl)-2-amino-benzimidazole) in complex with PTR1 revealed two alternative binding modes. In these complexes, previously unobserved protein movements and water-mediated protein-ligand contacts occurred, which prohibited a correct prediction of the binding modes. On the basis of the alternative binding mode of 1-(3,4-dichloro-benzyl)-2-amino-benzimidazole, derivatives were designed and selective PTR1 inhibitors with low nanomolar potency and favorable physicochemical properties were obtained.

PMID: 19527033 [PubMed - as supplied by publisher]

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