What's new for 'Trypanosomatids' in PubMed

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Sent on Saturday, 2012 June 02
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 10

1.	PLoS Pathog. 2012 May;8(5):e1002678. Epub 2012 May 24. Comparative Genomics Reveals Two Novel RNAi Factors in Trypanosoma brucei and Provides Insight into the Core Machinery. Barnes RL, Shi H, Kolev NG, Tschudi C, Ullu E. Source Department of Internal Medicine, Yale University, New Haven, Connecticut, United States of America. Abstract The introduction ten years ago of RNA interference (RNAi) as a tool for molecular exploration in Trypanosoma brucei has led to a surge in our understanding of the pathogenesis and biology of this human parasite. In particular, a genome-wide RNAi screen has recently been combined with next-generation Illumina sequencing to expose catalogues of genes associated with loss of fitness in distinct developmental stages. At present, this technology is restricted to RNAi-positive protozoan parasites, which excludes T. cruzi, Leishmania major, and Plasmodium falciparum. Therefore, elucidating the mechanism of RNAi and identifying the essential components of the pathway is fundamental for improving RNAi efficiency in T. brucei and for transferring the RNAi tool to RNAi-deficient pathogens. Here we used comparative genomics of RNAi-positive and -negative trypanosomatid protozoans to identify the repertoire of factors in T. brucei. In addition to the previously characterized Argonaute 1 (AGO1) protein and the cytoplasmic and nuclear Dicers, TbDCL1 and TbDCL2, respectively, we identified the RNA Interference Factors 4 and 5 (TbRIF4 and TbRIF5). TbRIF4 is a 3'-5' exonuclease of the DnaQ superfamily and plays a critical role in the conversion of duplex siRNAs to the single-stranded form, thus generating a TbAGO1-siRNA complex required for target-specific cleavage. TbRIF5 is essential for cytoplasmic RNAi and appears to act as a TbDCL1 cofactor. The availability of the core RNAi machinery in T. brucei provides a platform to gain mechanistic insights in this ancient eukaryote and to identify the minimal set of components required to reconstitute RNAi in RNAi-deficient parasites.
	PMID: 22654659 [PubMed - in process]

2.	J Biol Chem. 2012 May 31. [Epub ahead of print] Prostanoid receptor EP2 signaling protects T helper 2 cells from Balb/c mice against activation-induced cell death. Kaul V, Kaer LV, Das G, Das J. Source International Center for Genetic Engineering and Biotechnology, India; Abstract T helper 2 (Th2) cells play a central role in the progression of many diseases such as allergic airway inflammation (AAI), autoimmune diseases and infections caused by intracellular pathogens. Consequently, animals such as BALB/c mice, which exhibit a propensity for generating Th2 responses, are susceptible to AAI, type-II autoimmune diseases, and various infections induced by intracellular pathogens, namely, Leishmania. In contrast, C3H/OuJ mice have a tendency for generating Th1 responses and show resistance to these diseases. Here, we show that prostaglandin endoperoxide E2 (PGE2) selectively inhibits activation-induced cell death (AICD) of Th2 cells by signalling through its receptor E-prostanoid receptor 2 (EP2). Consequently, Th2 cells derived from BALB/c mice expressed very high levels of EP2. On the other hand, Th2 cells derived from C3H/OuJ mice expressed very low levels of EP2, which failed to support the survival of Th2 cells. Furthermore, we found that this effect of EP2 on Th2 cells from BALB/c mice was executed by a granzyme B (GrB)-mediated mechanism. EP2 belongs to a group of G-protein coupled receptors that are amenable to therapeutic targeting. Our findings therefore identify EP2 as a promising target for small molecule-directed immunomodulation.
	PMID: 22654101 [PubMed - as supplied by publisher]

3.	Pediatr Emerg Care. 2012 May 29. [Epub ahead of print] Visceral Leishmaniasis: A Common Cause of Post-Infectious Febrile Pancytopenia in Children in an Endemic Area: Experience of a Children's Tertiary Hospital. Alexandropoulou O, Tsolia M, Kossiva L, Giannaki M, Karavanaki K. Source From the *2nd Department of Pediatrics, University of Athens, "P&A Kyriakou" Children's Hospital; and †Department of Microbiology, "Aghia Sophia" Children's Hospital, Athens, Greece. Abstract BACKGROUND: Visceral leishmaniasis (VL, kala-azar) is caused by Leishmania spp, a parasite that is commonly encountered in Mediterranean countries. Leishmaniasis usually presents with fever, hepatosplenomegaly, lymphadenopathy, and pancytopenia. OBJECTIVES: The aim of the study was to prospectively examine the characteristics of cytopenia associated with VL and compare it with other post-infectious cytopenias observed in children with febrile illnesses. METHODS: We studied 112 children, aged (mean) 4.0 (SD, 3.8) years (range, 0-14 years), who were admitted to the pediatric ward because of febrile cytopenia associated with infections, during a 2-year period (March 2005 to June 2007). Study participants were investigated with measurement of acute-phase reactants, bacterial cultures, and serologic tests. RESULTS: Pancytopenia was detected in 9 (8%) of 112 patients (5 boys), with a mean age of 4.5 (SD, 3.0) years.The mean value of white blood cell was 3827 (SD, 1455)/mL; absolute neutrophil count, 1229 (SD, 655)/mL; hemoglobin, 8.3 (SD, 1.1) g/dL; and platelet count, 88,200 (SD, 20,186)/mL. All patients with pancytopenia had fever (mean duration, 8.9 [SD, 8.7] days) (maximum temperature, 39.5°C [SD, 0.6°C]) and hepatosplenomegaly (9/9), whereas 2 of 9 had lymphadenopathy. In these patients, a bone marrow aspiration was performed, and VL was detected in all 9 samples. They were treated with liposomal amphotericin B and had an excellent response rate. Pancytopenia resolved within a mean period of 17.6 (SD, 17.3) days (range, 8-60 days), and there was no relapse during a 2 years' follow-up. CONCLUSIONS: In endemic countries, leishmaniasis is the main cause of febrile pancytopenia among children in whom hematologic malignancy has been ruled out.
	PMID: 22653455 [PubMed - as supplied by publisher]

4.	Curr Opin Pharmacol. 2012 May 29. [Epub ahead of print] Antiparasitic agents: new drugs on the horizon. Mäser P, Wittlin S, Rottmann M, Wenzler T, Kaiser M, Brun R. Source Swiss Tropical and Public Health Institute, 4003 Basel, Switzerland; University of Basel, 4000 Basel, Switzerland. Abstract The need for new drugs against tropical parasites such as Plasmodium falciparum and Trypanosoma brucei is persistent since problems with resistance and toxicity are jeopardizing the currently available medicines. Public-private partnerships aiming to develop new medicines for malaria and sleeping sickness have, over the past 12 years, brought forward several drug candidates that have entered clinical trials. These are the synthetic peroxide OZ439 and the spiroindolone NITD609 against P. falciparum, fexinidazole and the oxaborole SCYX-7158 against T. brucei. A further class of high chemotherapeutic potential are the diamidines, novel members of which may serve as back-up compounds against trypanosomes and other parasites. Thus, finally, new therapeutic agents against malaria and sleeping sickness are within reach. Copyright © 2012 Elsevier Ltd. All rights reserved.
	PMID: 22652215 [PubMed - as supplied by publisher]

5.	J Enzyme Inhib Med Chem. 2012 May 31. [Epub ahead of print] New 5-(nitroheteroaryl)-1,3,4-thiadiazols containing acyclic amines at C-2: synthesis and SAR study for their antileishmanial activity. Tahghighi A, Emami S, Razmi S, Rezazade Marznaki F, Kabudanian Ardestani S, Dastmalchi S, Kobarfard F, Shafiee A, Foroumadi A. Source Department of Medicinal Chemistry, School of Pharmacy and Biotechnology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran. Abstract A novel series of 5-(5-nitrofuran-2-yl)-and 5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazole-2-amines bearing acyclic amine at C-2 position of thiadiazole ring were synthesized and evaluated in vitro against promastigote and amastigote forms of Leishmania major. The structure-activity of series was investigated by studying 40 compounds. The most active derivatives were hydroxypropylamino- and methoxypropylamino- analogs of 5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazole (compounds 29 and 32, respectively) with highest selectivity index (SI >12).
	PMID: 22651800 [PubMed - as supplied by publisher]

6.	Vector Borne Zoonotic Dis. 2012 May 31. [Epub ahead of print] Molecular Detection of Leishmania major kDNA from Wild Rodents in a New Focus of Zoonotic Cutaneous Leishmaniasis in an Oriental Region of Iran. Azizi K, Moemenbellah-Fard MD, Kalantari M, Fakoorziba MR. Source 1 Department of Medical Entomology, School of Health and Nutrition, Research Centre for Health Sciences, Shiraz University of Medical Sciences , Shiraz, Iran . Abstract Abstract Human cutaneous leishmaniasis is one of the most challenging public health issues in many tropical and subtropical countries of the world, including Iran. More than half (54%) of the new zoonotic cutaneous leishmaniasis (ZCL) cases among the Eastern Mediterranean countries were reported from Iran in 2008. The detection of Leishmania parasites in rodents is essential to incriminate them as probable reservoir hosts of ZCL infection. As a result of the annual detection of about 200-250 clinical ZCL cases in the Jask district of southern Iran, feral rodents were trapped, identified to species level, and examined for Leishmania presence by preparing routine blood smears on microscopic slides from 2007 to 2008. Overall, 27 Tatera indica, 17 Gerbillus nanus, 29 Meriones persicus, 26 M. hurrianae, and 7 M. libycus were identified. Females of T. indica, M. hurrianae, and G. nanus appeared to be naturally infected with the protozoan parasite, L. major. This is the first report of microscopic and molecular detection of this trypanosomatid parasite infecting these three rodents reported from Hormozgan province in southeast Iran. More than three-quarters (82%) of the parasite-infected rodents came from the eastern plain of this province, but none of the other rodents were found to be smear-positive or kinetoplast DNA-positive by PCR. M. hurrianae, G. nanus, and T. indica are therefore incriminated as three potential reservoir hosts of L. major in Oriental parts of Iran.
	PMID: 22651390 [PubMed - as supplied by publisher]

7.	Vector Borne Zoonotic Dis. 2012 May 31. [Epub ahead of print] Effect of Ambient Temperature on the Clinical Manifestations of Experimental Diffuse Cutaneous Leishmaniasis in a Rodent Model. Quiñonez-Díaz L, Mancilla-Ramírez J, Avila-García M, Ortiz-Avalos J, Berron A, González S, Paredes Y, Galindo-Sevilla N. Source 1 Ph.D. student for Medicine Research, ESM, IPN, Centro de Investigación, División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco , Villahermosa, Tabasco, México . Abstract Abstract Dermal species of Leishmania have a relatively broad temperature range for optimal growth in vitro, with temperature differences accompanied by a form change. This suggests that when the host is living in moderate temperatures (22°C), infection may proceed at temperatures lower than those that occur in tropical regions (32°C), and a different clinical expression of the disease due to a different parasitic form may result. The aim of this study was to investigate the effect of environmental temperature on the clinical expression of the disease. BALB/C mice infected with Leishmania mexicana were housed at 32°±2°C or 22°±1°C, and assessed for the development of inflammation and the presence of parasites in organs using PCR and immunohistology. The clinical expression of leishmaniasis at 32°C included inflammation at the site of inoculation with swelling of the nose and tail, whereas at 22°C, up to 50% of the infected mice developed dry exfoliative dermatitis with alopecia on the dorsum. In both cases, parasite colonization was confirmed in the skin, with parasites at more external locations at 22°C. Parasite visceralization was confirmed in all internal organs and glands in both cases based on PCR and immunohistology. In conclusion, the clinical expression of diffuse leishmaniasis by Leishmania mexicana in laboratory mice is modified by temperature, from nodular inflammation at 32°C, to dry exfoliative dermatitis and alopecia at 22°C, with parasite visceralization in both cases.
	PMID: 22651383 [PubMed - as supplied by publisher]

8.	Parasit Vectors. 2012 May 31;5(1):107. [Epub ahead of print] Spliced leader RNA silencing (SLS) - a programmed cell death pathway in Trypanosoma brucei that is induced upon ER stress. Michaeli S. Abstract ABSTRACT: Trypanosoma brucei is the causative agent of African sleeping sickness. The parasite cycles between its insect (procyclic form) and mammalian hosts (bloodstream form). Trypanosomes lack conventional transcription regulation, and their genes are transcribed in polycistronic units that are processed by trans-splicing and polyadenylation. In trans-splicing, which is essential for processing of each mRNA, an exon, the spliced leader (SL) is added to all mRNAs from a small RNA, the SL RNA. Trypanosomes lack the machinery for the unfolded protein response (UPR), which in other eukaryotes is induced under endoplasmic reticulum (ER) stress. Trypanosomes respond to such stress by changing the stability of mRNAs, which are essential for coping with the stress. However, under severe ER stress that is induced by blocking translocation of proteins to the ER, treatment of cells with chemicals that induce misfolding in the ER, or extreme pH, trypanosomes elicit the spliced leader silencing (SLS) pathway. In SLS, the transcription of the SL RNA gene is extinguished, and tSNAP42, a specific SL RNA transcription factor, fails to bind to its cognate promoter. SLS leads to complete shut-off of trans-splicing. In this review, I discuss the UPR in mammals and compare it to the ER stress response in T. brucei leading to SLS. I summarize the evidence supporting the notion that SLS is a programmed cell death (PCD) pathway that is utilized by the parasites to substitute for the apoptosis observed in higher eukaryotes under prolonged ER stress. I present the hypothesis that SLS evolved to expedite the death process, and rapidly remove from the population unfit parasites that, by elimination via SLS, cause minimal damage to the parasite population.
	PMID: 22650251 [PubMed - as supplied by publisher]

9.	Srp Arh Celok Lek. 2012 Mar-Apr;140(3-4):191-7. [Clinical characteristics and disease course in children with haemophagocytic lymphohistiocytosis treated at the University Children's Hospital in Belgrade]. [Article in Serbian] [No authors listed] Abstract INTRODUCTION: Haemophagocytic lymphohistiocytosis (HLH) is a disorder characterised by long-standing fever, splenomegaly and bicytopoenia or pancytopoenia. Lymphadenopathy, jaundice and neurological symptoms mayalsooccur. HLH may ensue in various forms of innate or acquired immunodeficiency with impaired cytotoxic lymphocyte function resulting in excessive macrophage activation. OBJECTIVE: To describe and analyse clinical characteristics of patients treated for HLH at the University Children's Hospital of Belgrade from August 2000 to August 2010. METHODS: Retrospective analysis of medical records. RESULTS: Diagnosis of HLH was established in 13 children (five boys and eight girls) aged from one month to 14 years. In six children HLH was secondary (to visceral leishmaniasis in two, Ebstein-Barr virus infection in one, Langerhans' cell histiocytosis in one and systemic juvenile rheumatoid arthritis in two). Of the remaining seven patients, genes for perforin and syntaxin 11 were examined in two and no mutations were found. Of the remaining seven patients, genes encoding perforin and syntaxin 11 were analyzed in two, but no mutations were found. All children had fever, splenomegaly, cytopoenias, hyperferritinaemia and hypertriglyceridaemia, but haemophagocytosis was seen in only six (46.1%). Six children were cured (four with secondary HLH and two with primary HLH).Two children are undergoing treatment, while five succumbed (three before treatment could be administered and two due to complications). In four of the six cured children, HLH arose in the first year of life. Cure rate in those who underwent haematopoietic stem cell transplantation was 2/3. CONCLUSION: Results underscore the importance of timely diagnosis and treatment of HLH, warranting that in all children with fever, splenomegaly and/or cytopoenias, with or without haemophagocytosis, HLH be actively sought.
	PMID: 22650106 [PubMed - in process]

10.	Enferm Infecc Microbiol Clin. 2012 Feb;30(2):64-9. Epub 2011 Nov 12. [Serological profile of immigrant pregnant women against HIV, HBV, HCV, rubella, Toxoplasma gondii, Treponema pallidum, and Trypanosoma cruzi]. [Article in Spanish] Santiago B, Blázquez D, López G, Sainz T, Muñoz M, Alonso T, Moro M. Source Servicio de Pediatría, Hospital Universitario Clínico San Carlos, Madrid, España. bsantiagogarcia@hotmail.com Abstract INTRODUCTION: The increase in immigration is changing the prevalence of mother to child infectious diseases. Our aim is to determine the serological profile of foreign pregnant women against these infections. METHODS: A retrospective cross sectional study was performed in a tertiary hospital from Madrid between August 2007 and October 2008. The seroprevalence against HIV, HBV, HCV, rubeola, T. gondii, T. pallidum and T. cruzi was determined in every pregnant immigrant, as well as in a representative group of Spanish pregnant women. RESULTS: A total of 2526 immigrant and 157 Spanish pregnant women were studied. None of the Spanish and 0.5% of the foreigners showed antibodies against HIV; 18.9% of them were Sub-Saharan women. Antigen HBs was detected in 2% of the immigrant women and in 1.1% of the Spanish women. Asian women had the highest rate of type B Hepatitis (10.9%). There was 0.9% of type C Hepatitis among the immigrants and 1% among the Spanish. Within the cases with RPR ≥ 1/8, 1.6% were immigrants, most of whom were Latin American. Thirty-one per cent of the immigrants showed antibodies against T. gondii (37.5% from Central America, 2.5% from the Far East). More than 95% of the Spanish women had antibodies against Rubella, this being lower in the rest of the areas (75.5% in Sub-Saharan Africa). T. cruzi infection was detected in 12.1% of the Bolivian women studied. CONCLUSION: The prevalence of mother-to-child transmitted infections depends on the origin of pregnant women. Knowledge of these differences may lead to improved control these diseases. Copyright © 2010 Elsevier España, S.L. All rights reserved.
	PMID: 22079225 [PubMed - indexed for MEDLINE]
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