What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2010 Nov 09
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.	Biotechnol J. 2010 Nov;5(11):1198-206. Increased expression of recombinant human tissue plasminogen activator in Leishmania tarentolae. Hemayatkar M, Mahboudi F, Majidzadeh-A K, Davami F, Vaziri B, Barkhordari F, Adeli A, Mahdian R, Davoudi N. Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. Abstract Recombinant tissue plasminogen activator (rt-PA) is one of the most important thrombolytic agents for treating cardiovascular obstructions such as stroke. Glycoprotein rt-PA is a serine protease, consisting of 527 amino acids of which 35 are cysteine residues. A variety of recombinant protein expression systems have been developed for heterologous gene expression in prokaryotic and eukaryotic hosts. In recent years, Leishmania tarentolae has been considered because of its safety aspects and special attributes in expression of complex proteins. In this study, two expression cassettes, each one including two copies of t-PA cDNA, were used for integration into the L. tarentolae genome by electroporation. Transformed clones were selected in the presence of appropriate antibiotics. Expression of active rt-PA was confirmed by Western blot and Zymography tests. Real-time PCR analysis was applied to investigate the presence of multiple t-PA gene copies in the parasite genome. Correlation of t-PA gene dosage and production rate was confirmed with real-time PCR. It was shown that the expression level of rt-PA in L. tarentolae is at least 480 IU/mL of culture media. This concentration of rt-PA is seven times higher than what was reported in previous studies in L. tarentolae and some other eukaryotic systems.
	PMID: 21058320 [PubMed - in process]

2.	Planta Med. 2010 Nov 5. [Epub ahead of print] Antileishmanial Sesquiterpenes from the Brazilian Red Alga Laurencia dendroidea. da Silva Machado FL, Pacienza-Lima W, Rossi-Bergmann B, de Souza Gestinari LM, Fujii MT, Campos de Paula J, Costa SS, Lopes NP, Kaiser CR, Soares AR. Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Abstract Investigation of the bioactive crude extracts from two populations of the red alga LAURENCIA DENDROIDEA from the southeastern Brazilian coast led to the identification of five sesquiterpenes: (+)-obtusane ( 1), a triquinane derivative ( 2), (-)-elatol ( 3), obtusol ( 4), and cartilagineol ( 5). An antileishmanial bioassay against LEISHMANIA AMAZONENSIS was conducted for crude lipophilic extracts and for sesquiterpenes 2, 3, and 4. Compounds 3 and 4 displayed IN VITRO and IN VIVO leishmanicidal activity and very low cytotoxicity. © Georg Thieme Verlag KG Stuttgart · New York.
	PMID: 21058243 [PubMed - as supplied by publisher]

3.	J Pharmacol Exp Ther. 2010 Nov 5. [Epub ahead of print] The distribution of nifurtimox across the healthy and trypanosome-infected murine blood-brain and blood-CSF barriers. Jeganathan S, Sanderson L, Dogruel M, Rodgers J, Croft S, Thomas SA. 1 King's College London; Abstract Nifurtimox, an anti-parasitic drug, is used to treat American trypanosomiasis (Chagas disease) and has shown promise in treating CNS-stage human African trypanosomiasis (HAT; sleeping sickness). In combination with other anti-parasitic drugs, the efficacy of nifurtimox against HAT improves, although why this happens is unclear. Studying how nifurtimox crosses the blood-brain barrier (BBB) and reaches the CNS may clarify this issue and is the focus of this study. To study the interaction of nifurtimox with the blood-CNS interfaces, we used the in situ brain/choroid plexus perfusion technique in healthy and trypanosome infected mice, and the isolated incubated choroid plexus. Results revealed that nifurtimox could cross the healthy and infected blood-brain and blood-CSF barriers (K(in) brain parenchyma was 50.8±9.0μl.min(-1).g(-1)). In fact the loss of barrier integrity associated with trypanosome infection failed to change the distribution of [(3)H]nifurtimox to any significant extent suggesting there is not an effective paracellular barrier for [(3)H]nifurtimox entry into the CNS. Our studies also indicate that [(3)H]nifurtimox is not a substrate for P-glycoprotein, an efflux transporter expressed on the luminal membrane of the BBB. However, there was evidence of [(3)H]nifurtimox interaction with transporters at both the blood-brain and blood-CSF barriers as demonstrated by cross-competition studies with the other anti-trypanosomal agents, eflornithine, suramin, melarsoprol and pentamidine. Consequently, CNS efficacy may be improved with nifurtimox-pentamidine combinations, but over time may be reduced when nifurtimox is combined with eflornithine, suramin or melarsoprol.
	PMID: 21057057 [PubMed - as supplied by publisher]

4.	Hum Exp Toxicol. 2010 Nov 5. [Epub ahead of print] Biochemical changes in the kidney and liver of rats following administration of ethanolic extract of Psidium guajava leaves. Adeyemi OS, Akanji MA. Department of Chemical Sciences, College of Natural Sciences, Redeemer's University, Nigeria. Abstract Furtherance to a previous report on the anti-trypanosomal properties of Psidium guajava aqueous leaf extract in rats experimentally infected with Trypanosoma brucei brucei, we have evaluated the effects of the daily intraperitoneal administration of P. guajava leaf extract to rats on the activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and acid phosphatase (ACP) in the kidney, liver and serum. The results obtained revealed that the administration of the extract produced significant increase in the serum activities of AST, ALT, ALP and ACP when compared with the control (p < 0.05). Also AST, ALT and ALP and ACP activities in the tissues of animals administered the extract revealed inconsistent changes (p < 0.05) relative to control. The increase in the serum activity of ALP may be an indicator that there was a likely compromise to the integrity of the plasma membrane as a result of the ethanolic extract administration. This could have caused leakages of the other enzymes investigated, which may explain the corresponding increases in the serum activities of AST, ALT and ACP observed.
	PMID: 21056949 [PubMed - as supplied by publisher]

5.	Microbes Infect. 2010 Nov 4. [Epub ahead of print] Toll-like receptor 4 polymorphisms predispose to cutaneous leishmaniasis. Ajdary S, Ghamilouie MM, Alimohammadian MH, Riazi-Rad F, Pakzad SR. Immunology department, Pasteur Institute of Iran, Pasteur Ave., Tehran, IR-Iran. Abstract The clinical spectrum of cutaneous leishmaniasis (CL) is extremely variable. Studies in experimental leishmaniasis have revealed a role for TLR4 in control of infection. In the present study the associations between TLR4 mutations (Asp299Gly and Thr399Ile) with outcome of CL have been investigated. Genotyping for Asp299Gly and Thr399Ile was performed in patients with chronic (N=22) and acute (N=61) CL, asymptomatic (N=45) and healthy leishmanin skin test negative individuals (N=75). The results showed the frequency of the Asp299Gly genotype was increased in patients with chronic disease (OR 25.3, 95% CI 5.2-115.6, P<0.001) and patients with acute disease (OR 8.03, 95% CI 1.7-37.7, P=0.006) compared to LST negative subjects. Thr399Ileu genotype was significantly overrepresented among patients with chronic disease (27.3%, P<0.001), patients with acute disease (13.1%, P=0.016), and asymptomatic donors (15.6%, P=0.008) in comparison with LST negative normal group (1.3%). Both variants were found together more frequently in patients with chronic disease compared to the patients with acute disease (P=0.045), and asymptomatic donors (P=0.045). The results provide evidence that polymorphisms of TLR4 gene may lead to the increased susceptibility to and severity of infection by L. major. The concomitant carriage of both mutations increases the susceptibility of individuals to CL. Copyright © 2010. Published by Elsevier SAS.
	PMID: 21056683 [PubMed - as supplied by publisher]

6.	Infect Genet Evol. 2010 Nov 2. [Epub ahead of print] Evolutionary Genomics of Glossina morsitans immune-related CLIP Domain Serine Proteases and Serine Protease Inhibitors. Mwangi S, Murungi E, Jonas M, Christoffels A. Address: South African National Bioinformatics Institute, University of the Western Cape, Private Bag X17, Modderdam Road, Bellville, Cape Town, South Africa. Abstract Several species of haematophagous tsetse flies (genus Glossina) are vectors for trypanosomes, the parasitic protozoans that cause Human African Trypanosomiasis (HAT). Although there was a reduced incidence of HAT in the mid 1960's, decreased disease surveillance has led to a resurgence of HAT in sub-Saharan Africa. Despite being efficient vectors for HAT transmission, the prevalence of G. morsitans infection by trypanosomes in the wild is surprisingly minimal. The precise mechanisms by which G. morsitans remain refractory to trypanosome infection are largely unknown although it has been demonstrated that G. morsitans mounts a strong immune response to invading pathogens. This study identifies G. morsitans immune-related CLIP domain serine proteases and their inhibitors, serine protease inhibitors (serpin) genes. It further establishes their evolutionary relationships with counterparts in Drosophila melanogaster, Anopheles gambiae, Bombyx mori, Manduca sexta and Culex quinquefasciatus. Multiple sequence alignments show conservation of most secondary structure elements for both CLIPs and serpins. Amino acid composition of the serpin reactive site loop (RSL) indicates that the G. morsitans serpins act through an inhibitory mechanism to the target serine protease. Similar to D. melanogaster and unlike A. gambiae, the transcriptome data suggest that G. morsitans does not contain gene expansions in their CLIP-domain serine protease and serpin families. The presence of alternatively spliced variants in the G. morsitans serpins transcriptome data mirrors that of the D. melanogaster transcriptome. Copyright © 2010 Elsevier B.V. All rights reserved.
	PMID: 21055483 [PubMed - as supplied by publisher]

7.	Mol Biochem Parasitol. 2010 Nov 2. [Epub ahead of print] A Rapid; Efficient and Economical Method for Generating Leishmanial Gene Targeting Constructs. Fulwiler AL, Soysa DR, Ullman B, Yates PA. Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, Oregon 97239. Abstract Targeted gene replacement is a powerful tool in Leishmania genetics that can be time-consuming to implement. One tedious aspect that delays progress is the multi-step construction of gene targeting vectors. To accelerate this process, we developed a streamlined method that allows the assembly of a complete targeting vector from all its constituent parts in a single-step multi-fragment ligation. The individual components to be assembled are flanked by sites for the restriction endonuclease SfiI that generates non-identical, non-palindromic three base 3'-overhangs designed to allow annealing and ligation of the parts only in the proper order. The method was optimized by generating constructs for targeting the Leishmania donovani inosine monophosphate dehydrogenase gene (LdIMPDH) encoding six different drug resistance markers, and was found to be rapid and efficient. These constructs were successfully employed to generate heterozygous LdIMPDH gene replacement mutants. This method is adaptable for generating targeting vectors for a variety of species. Copyright © 2010. Published by Elsevier B.V.
	PMID: 21055426 [PubMed - as supplied by publisher]

8.	Int J Parasitol. 2010 Nov 2. [Epub ahead of print] Miltefosine, a promising novel agent for schistosomiasis mansoni. Eissa MM, El-Azzouni MZ, Amer EI, Baddour NM. Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt. Abstract This research aims towards developing an alternative antischistosomal drug using miltefosine, which is primarily used in the treatment of leishmaniasis. The treatment and control of schistosomiasis, a notable Neglected Tropical Disease (NTD), rely on a single drug, praziquantel (PZQ). The dependency on PZQ exclusively is quite alarming, given the spread of the disease (over 200 million people infected and close to 800 million people at risk in three continents) and the threat of drug resistance. This study shows that the oral administration of miltefosine in a daily dose of 20 mg/kg for five successive days to mice infected with either invasive, juvenile or adult stages of Schistosoma mansoni resulted in significant reduction of worm burden, hepatic granulomata size and amelioration of hepatic pathology. Scanning Electron Microscopy revealed that miltefosine induced severe tegumental damage in adult schistosomes. In conclusion, we believe this is the first study highlighting miltefosine as a promising novel agent for schistosomiasis mansoni. Copyright © 2010. Published by Elsevier Ltd.
	PMID: 21055404 [PubMed - as supplied by publisher]

9.	Acta Cytol. 2010 Sep-Oct;54(5 Suppl):946-8. Fine needle aspiration of a lymph node in an HIV patient with chronic infection by leishmania: a case report. de Faria FB, Barroca H. Anatomic Pathology Service, Hospital of São, 4200-319 Porto, Portugal. barretofilomena@gmail.com Abstract BACKGROUND: Lymphadenopathy is one of the earliest and commonest manifestations in HIV patients. Fine needle aspiration cytology is an accurate, common procedure in the evaluation of lymphadenopathy in HIV-positive patients. The most frequent etiology of this clinical manifestation, in Western studies, is the presence of reactive hyperplasia due to the HIV itself and infectious diseases with opportunistic agents, namely Mycobacterium. The diagnosis of other microorganisms, such as fungi, helminthes and protozoa, is less likely, and most cases are reported as curiosities. CASE: Chronic visceral leishmaniasis occurred in an HIV-1 patient. Fine needle aspiration biopsy was performed in an axillary lymph node during the course of follow-up. The lymph node aspirates showed numerous macrophages, carrying several intracellular microorganisms (Leishmania amastigotes). CONCLUSION: The cytologic diagnosis offered no major challenge, but the differential diagnosis with other intracellular infectious agents that can also affect HIV patients should always be considered. In this context, we reviewed the HIV patients with lymphadenopathy seen in our hospital and who underwent fine needle biopsy in the last 5 years. From a series of 201 patients and 250 fine needle aspiration biopsy samples, this was the only case of leishmaniasis to date.
	PMID: 21053575 [PubMed - in process]

10.	Parasitology. 2010 Aug;137(9):1333-41. Epub 2010 May 6. The silicon trypanosome. Bakker BM, Krauth-Siegel RL, Clayton C, Matthews K, Girolami M, Westerhoff HV, Michels PA, Breitling R, Barrett MP. Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. b.m.bakker@med.umcg.nl Abstract African trypanosomes have emerged as promising unicellular model organisms for the next generation of systems biology. They offer unique advantages, due to their relative simplicity, the availability of all standard genomics techniques and a long history of quantitative research. Reproducible cultivation methods exist for morphologically and physiologically distinct life-cycle stages. The genome has been sequenced, and microarrays, RNA-interference and high-accuracy metabolomics are available. Furthermore, the availability of extensive kinetic data on all glycolytic enzymes has led to the early development of a complete, experiment-based dynamic model of an important biochemical pathway. Here we describe the achievements of trypanosome systems biology so far and outline the necessary steps towards the ambitious aim of creating a 'Silicon Trypanosome', a comprehensive, experiment-based, multi-scale mathematical model of trypanosome physiology. We expect that, in the long run, the quantitative modelling enabled by the Silicon Trypanosome will play a key role in selecting the most suitable targets for developing new anti-parasite drugs.
	PMID: 20444304 [PubMed - indexed for MEDLINE]
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