What's new for 'Trypanosomatids' in PubMed

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Sent on Wednesday, 2012 March 07
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 - 7 of 7

1.	PLoS One. 2012;7(2):e32642. Epub 2012 Feb 29. Discovery of Inhibitors of Leishmania β-1,2-Mannosyltransferases Using a Click-Chemistry-Derived Guanosine Monophosphate Library. van der Peet P, Ralton JE, McConville MJ, Williams SJ. Source School of Chemistry, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia. Abstract Leishmania spp. are a medically important group of protozoan parasites that synthesize a novel intracellular carbohydrate reserve polymer termed mannogen. Mannogen is a soluble homopolymer of β-1,2-linked mannose residues that accumulates in the major pathogenic stages in the sandfly vector and mammalian host. While several steps in mannogen biosynthesis have been defined, none of the enzymes have been isolated or characterized. We report the development of a simple assay for the GDP-mannose-dependent β-1,2-mannosyltransferases involved in mannogen synthesis. This assay utilizes octyl α-d-mannopyranoside to prime the formation of short mannogen oligomers up to 5 mannose residues. This assay was used to screen a focussed library of 44 GMP-triazole adducts for inhibitors. Several compounds provided effective inhibition of mannogen β-1,2-mannosyltransferases in a cell-free membrane preparation. This assay and inhibitor compounds will be useful for dissecting the role of different mannosyltransferases in regulating de novo biosynthesis and elongation reactions in mannogen metabolism.
	PMID: 22393429 [PubMed - in process]
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2.	Parasitol Res. 2012 Mar 6. [Epub ahead of print] Augmentation of antileishmanial efficacy of miltefosine in combination with tuftsin against experimental visceral leishmaniasis. Shakya N, Sane SA, Haq W, Gupta S. Source Division of Parasitology, Central Drug Research Institute (CSIR), Chattar Manzil Palace, M.G. Road, Lucknow, 226001, Uttar Pradesh, India. Abstract Current drugs for the treatment of visceral leishmaniasis are inadequate, and their efficacies are also compromised due to suppression of immune function during the course of infection. Miltefosine is the only promising orally active antileishmanial drug, but due to its long half-life, there is risk of development of resistance. To overcome these problems, efforts are needed to develop combination therapy of miltefosine with effective immunostimulating agents where a decrease of parasitic burden and simultaneous enhancement of adaptive immunity can be achieved. In the present study, we have explored the antileishmanial efficacy of a subcurative dose of miltefosine in combination with free as well as liposomal palmitoyl tuftsin (p-tuftsin) using a Leishmania donovani/BALB/c mouse model. When miltefosine (2.5 mg/kg for 5 days) was given with free p-tuftsin, the inhibitory effect was significantly increased from 49.6% to 66% (P < 0.01), which was further enhanced up to 81% (P < 0.001) when given after liposomal encapsulation of p-tuftsin. Significant enhancement in parasitic inhibition (93%, P < 0.01) was witnessed when animals were co-administered with liposomal p-tuftsin + 5 mg/kg × 5 days dose of miltefosine (72.1%). Enhancement in the production of Th1 cytokines (IL-12, TNF-α, and IFN-γ), reactive oxygen, and nitrogen metabolites was witnessed in the combination group. A remarkable increase in phagocytosis index was also observed indicating overall immunological enhancement to antileishmanial activity of miltefosine by p-tuftsin.
	PMID: 22392136 [PubMed - as supplied by publisher]
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3.	J Med Chem. 2012 Mar 6. [Epub ahead of print] Synthesis and Structure-Activity Analysis of New Phospho nium Salts with Potent Activity against African Trypanosomes. Taladriz A, Healy A, Flores Pérez EJ, Herrero García V, Ríos Martínez C, Alkhaldi AA, Eze AA, Kaiser M, de Koning HP, Chana A, Dardonville C. Source Instituto de Química Médica, IQM-CSIC , Juan de la Cierva 3, E-28006 Madrid, Spain. Abstract A series of 73 bisphosphonium salts and 10 monophosphonium salt derivatives were synthesized and tested in vitro against several wild type and resistant lines of Trypanosoma brucei (T. b. rhodesiense STIB900, T. b. brucei strain 427, TbAT1-KO, and TbB48). More than half of the compounds tested showed a submicromolar EC(50) against these parasites. The compounds did not display any cross-resistance to existing diamidine therapies, such as pentamidine. In most cases, the compounds displayed a good selectivity index versus human cell lines. None of the known T. b. brucei drug transporters were required for trypanocidal activity, although some of the bisphosphonium compounds inhibited the low affinity pentamidine transporter. It was found that phosphonium drugs act slowly to clear a trypanosome population but that only a short exposure time is needed for irreversible damage to the cells. A comparative molecular field analysis model (CoMFA) was generated to gain insights into the SAR of this class of compounds, identifying key features for trypanocidal activity.
	PMID: 22390399 [PubMed - as supplied by publisher]
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4.	Asian Pac J Trop Med. 2012 Feb;5(2):110-2. High resolution manometric findings in patients with Chagas' disease esophagopathy. Silva LC, Vicentine FP, Herbella FA. Source Department of Surgery, Escola Paulista de Medicina, Federal University of Sao Paulo, Sao Paulo, Brazil. Abstract OBJECTIVE: To describe high resolution manometry features of a population of symptomatic patients with Chagas' disease esophagopathy (CDE). METHODS: Sixteen symptomatic dysphagic patients with CDE [mean age (54.81±13.43) years, 10 women] were included in this study. All patients underwent a high resolution manometry. RESULTS: Mean lower esophageal sphincter (LES) extension was (3.02±1.17) cm with a mean basal pressure of (15.25±7.00) mmHg. Residual pressure was (14.31±9.19) mmHg. Aperistalsis was found in all 16 patients. Achalasia with minimal esophageal pressurization (type 1) was present in 25% of patients and achalasia with esophageal compression (type 2) in 75%, according to the Chicago Classification. Upper esophageal sphincter (UES) mean basal pressure was (97.96±54.22) mmHg with a residual pressure of (12.95±6.42) mmHg. CONCLUSIONS: Our results show that LES was hypotensive or normotensive in the majority of the patients. Impaired relaxation was found in a minority of our patients. Aperistalsis was seen in 100% of patients. UES had impaired relaxation in a significant number of patients. Further clinical study is needed to investigate whether manometric features can predict outcomes following the studies of idiopathic achalasia. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.
	PMID: 22221752 [PubMed - indexed for MEDLINE]
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5.	Rev Chilena Infectol. 2011 Jun;28(3):276-81. Epub 2011 Jul 14. [Aldo Castellani and the expeditions of the Royal Society to the black sleep' s country]. [Article in Spanish] Ledermann D W. Source Socio Honorario Sociedad Chilena de Infectología. revinf@sochinf.cl Abstract At the beginning the investigation on infectious diseases was plenty of adventures in exotic countries. The efforts of the English investigators, headed by Patrick Manson, gave birth to the "tropical" medicine and "tropical" diseases, like the sleeping sickness, which was sweeping the country north to the Victoria Lake in 1901. The Royal Society of London sent two Commissions in search of the etiological agent. Aldo Castellani was decisive for the failure of the first - Low, Castellani, Christy,1902 - because even he saw Trypanosoma in samples of some patients, he did not appreciate his discovery; and decisive also for the success of the second -Bruce, Nabarro, Greig, 1903 - when he and Bruce recognized this Trypanosoma as the etiological agent. Following these expeditions, Low developed a brilliant career in England, Christy a life of investigation mixed up with adventures through Asia and Africa and Castellani a long life of lights and shadows in many lands. Free Article
	PMID: 21879157 [PubMed - indexed for MEDLINE]
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6.	Zoonoses Public Health. 2011 Dec;58(8):582-8. doi: 10.1111/j.1863-2378.2011.01407.x. Epub 2011 May 6. Sonographical and serological survey of human cystic echinococcosis and analysis of risk factors associated with seroconversion in rural communities of Kerman, Iran. Harandi MF, Moazezi SS, Saba M, Grimm F, Kamyabi H, Sheikhzadeh F, Sharifi I, Deplazes P. Source Leishmaniasis Research Center and Department of Parasitology School of Medicine, Kerman University of Medical Sciences, Iran. fasihi@kmu.ac.ir  Abstract Cystic echinococcosis (CE) caused by larval stage of Echinococcus granulosus, is an endemic zoonosis in Iran particularly in rural regions. The objective of this study was to determine the prevalence of CE among rural communities in Kerman using ultrasonography (US) and serology. Kerman Province, in southeastern Iran, is the largest province, with 2.9 million inhabitants. A sample of 1140 individuals (200 males and 940 females) was selected by randomized cluster sampling in 2006-2008. After acquiring informed consent for each participant a questionnaire was filled, complete abdominal US in supine position was carried out and 5 ml blood was collected for ELISA test. Two hydatid cases (0.2%) were detected by ultrasound. Serological results showed 7.3% seropositivity, and females (8.3%) were significantly more positive than males (2.1%). There were significant difference between CE seropositivity and sex, age and occupation. Residents of desert regions (Shahdad, Andouhjerd and Golbaf) were 2.5 times more likely to be seropositive than mountainous regions with better socioeconomic status (OR = 2.5; 95% CI = 1.09-5.95). Dog ownership does not appear to be a significant risk factor for CE in the region. Only about 10% of households own dogs, usually only one dog. However, the stray dog population of Kerman province is estimated at 145 000-480 000 (3.5-11.5 times the owned dog population). Infection in humans and animals would appear to come mostly from infected stray dogs. Management of stray dog population could make major progress in control of hydatid disease. In addition, proper washing of vegetables decreased probability of infection by 53% (OR = 0.47; 95% CI = 0.26-0.84). The serological study showed that many people, especially women, had been exposed to Echinococcus eggs and had seroconverted but were not infected. © 2011 Blackwell Verlag GmbH.
	PMID: 21824361 [PubMed - indexed for MEDLINE]
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7.	Antimicrob Agents Chemother. 2011 Oct;55(10):4765-73. Epub 2011 Aug 1. The trypanocidal activity of amidine compounds does not correlate with their binding affinity to Trypanosoma cruzi kinetoplast DNA. Daliry A, Pires MQ, Silva CF, Pacheco RS, Munde M, Stephens CE, Kumar A, Ismail MA, Liu Z, Farahat AA, Akay S, Som P, Hu Q, Boykin DW, Wilson WD, De Castro SL, Soeiro MN. Source Laboratório de Biologia, Celular, IOC, FIOCRUZ, Av. Brasil 4365, Manguinhos 21045-900, Rio de Janeiro, RJ, Brazil. Abstract Due to limited efficacy and considerable toxicity, the therapy for Chagas' disease is far from being ideal, and thus new compounds are desirable. Diamidines and related compounds such as arylimidamides have promising trypanocidal activity against Trypanosoma cruzi. To better understand the mechanism of action of these heterocyclic cations, we investigated the kinetoplast DNA (kDNA) binding properties and trypanocidal efficacy against T. cruzi of 13 compounds. Four diamidines (DB75, DB569, DB1345, and DB829), eight arylimidamides (DB766, DB749, DB889, DB709, DB613, DB1831, DB1852, and DB2002), and one guanylhydrazone (DB1080) were assayed in thermal denaturation (T(m)) and circular dichroism (CD) studies using whole purified T. cruzi kDNA and a conserved synthetic parasite sequence. The overall CD spectra using the whole kDNA were similar to those found for the conserved sequence and were indicative of minor groove binding. Our findings showed that some of the compounds that exhibited the highest trypanocidal activities (e.g., DB766) caused low or no change in the T(m) measurements. However, while some active compounds, such as DB766, induced profound alterations of kDNA topology, others, like DB1831, although effective, did not result in altered T(m) and CD measurements. Our data suggest that the strong affinity of amidines with kDNA per se is not sufficient to generate and trigger their trypanocidal activity. Cell uptake differences and possibly distinct cellular targets need to be considered in the final evaluation of the mechanisms of action of these compounds. PMCID: PMC3186963 [Available on 2012/4/1]
	PMID: 21807972 [PubMed - indexed for MEDLINE]
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