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 - 10 of 16

1.	Curr Protoc Immunol. 2011 Apr;Chapter 14:Unit14.23. Measuring the killing of intracellular pathogens: leishmania. Stenger S, van Zandbergen G. Institute for Medical Microbiology and Hygiene, University Hospital of Ulm, Ulm, Germany. Abstract Macrophages are professional phagocytes serving as a first line of defence against pathogenic organisms. Macrophages are equipped with efficient effector functions to kill invading microorganisms. The first important mechanism of macrophage host-defence is phagocytosis of pathogens. Subsequently, internalized pathogens are targeted for destruction in maturating phagolysosomal compartments. This process is mediated by lysosomal proteases and an acidified compartment. To investigate macrophages' killing potential in this chapter, we describe an assay based on human primary cells infected with the obligatory intracellular parasite Leishmania. For this pathogen the macrophage has a dual role. The parasite can use macrophages for its intracellular multiplication, but at the same time host macrophages, upon stimulation, can kill the parasite. Curr. Protoc. Immunol. 93:14.23.1-14.23.12. © 2011 by John Wiley & Sons, Inc.
	PMID: 21462165 [PubMed - in process]
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2.	Korean J Parasitol. 2011 Mar;49(1):17-23. Epub 2011 Mar 18. Miltefosine-Induced Apoptotic Cell Death on Leishmania major and L. tropica Strains. Khademvatan S, Gharavi MJ, Rahim F, Saki J. Department of Medical Parasitology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Abstract The aim of this study was to assess the cytotoxic effects of various concentrations of miltefosine on Leishmania major (MRHO/IR/75/ER) and L. tropica (MHOM/IR/02/Mash10) promastigotes and to observe the programmed cell death features. The colorimetric MTT assay was used to find L. major and L. tropica viability and the obtained results were expressed as 50% inhibitory concentration (IC50). Also, 50% effective doses (ED50) for L. major and L. tropica amastigotes were also determined. Annexin-V FLUOS staining was performed to study the cell death properties of miltefosine using FACS analysis. Qualitative analysis of the total genomic DNA fragmentation was performed by agarose gel electrophoresis. Furthermore, to observe changes in cell morphology, promastigotes were examined using light microscopy. In both strains of L. major and L. tropica, miltefosine induced dose-dependent death with features of apoptosis, including cell shrinkage, DNA laddering, and externalization of phosphatidylserine. The IC50 was achieved at 22 µM and 11 µM for L. major and L. tropica after 48 hr of incubation, respectively. ED50 of L. major and L. tropica amastigotes were 5.7 µM and 4.2 µM, respectively. Our results indicate that miltefosine induces apoptosis of the causative agent of cutaneous leishmaniasis in a dose-dependent manner. Interestingly, L. major did not display any apoptotic changes when it was exposed to miltefosine in concentrations sufficient to kill L. tropica.
	PMID: 21461264 [PubMed - in process]
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3.	Am J Trop Med Hyg. 2011 Apr;84(4):566-8. Central nervous system toxicity associated with liposomal amphotericin B therapy for cutaneous leishmaniasis. Glasser JS, Murray CK. Brooke Army Medical Center, Fort Sam Houston, Texas; Uniformed Services University of the Health Sciences, Bethesda, Maryland; University of Texas Health Science Center at San Antonio, San Antonio, Texas. Abstract Abstract. AmBisome (liposomal amphotericin B) is used for prophylaxis and treatment of fungal infections, treatment of visceral leishmaniasis, and more recently, treatment of cutaneous leishmaniasis. Although the package insert cites neurologic toxicities in up to 20% of cases, review of the literature did not reveal any specific cases describing this side effect, particularly in a patient without comorbidities. We describe a healthy 38-year-old male treated with liposomal amphotericin B for cutaneous leishmaniasis acquired during military duties in Iraq. Shortly after completion of his treatment course, he reported memory difficulties and confusion. Further evaluation revealed no other source, and his cognitive issues were attributed to liposomal amphotericin B toxicity. These issues resolved over a few weeks, which is consistent with data about the drug's tissue penetration and metabolism available in the literature. This is a potential side effect of liposomal amphotericin B that can be observed in otherwise healthy patients.
	PMID: 21460011 [PubMed - in process]
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4.	Am J Trop Med Hyg. 2011 Apr;84(4):562-5. Cutaneous leishmaniasis after travel to cyprus and successful treatment with mil tefosine. Poeppl W, Walochnik J, Pustelnik T, Auer H, Mooseder G. Department of Dermatology and Tropical Medicine, Military Hospital Vienna, Austria; Institute of Specific Prophylaxis and Tropical Medicine, Department of Medical Parasitology, Medical University of Vienna, Vienna, Austria. Abstract Abstract. A patient presenting with an atypical manifestation of cutaneous leishmaniasis after travel to Cyprus was successfully treated with miltefosine. The K26 typing revealed a hitherto undescribed strain of the Leishmania donovani/infantum complex as the causing agent.
	PMID: 21460010 [PubMed - in process]
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5.	Am J Trop Med Hyg. 2011 Apr;84(4):556-561. Polymerase Chain Reaction Detection of Leishmania kDNA from the Urine of Peruvian Patients with Cutaneous and Mucocutaneous Leishmaniasis. Veland N, Espinosa D, Valencia BM, Ramos AP, Calderon F, Arevalo J, Low DE, Llanos-Cuentas A, Boggild AK. Instituto de Medicina Tropical "Alexander von Humboldt," Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru; Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia; Laboratories Branch, Ontario Agency for Health Protection and Promotion, Etobicoke, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Hospital Nacional Cayetano Heredia, Lima, Peru; Tropical Disease Unit, Division of Infectious Diseases, Toronto General Hospital, Toronto, Canada. Abstract Abstract. We hypothesized that Leishmania kDNA may be present in urine of patients with cutaneous leishmaniasis (CL). Urine samples and standard diagnostic specimens were collected from patients with skin lesions. kDNA polymerase chain reaction (PCR) was performed on samples from patients and 10 healthy volunteers from non-endemic areas. Eighty-six of 108 patients were diagnosed with CL and 18 (21%) had detectable Leishmania Viannia kDNA in the urine. Sensitivity and specificity were 20.9% (95% confidence interval [CI] 12.3-29.5%) and 100%. Six of 8 patients with mucocutaneous involvement had detectable kDNA in urine versus 12 of 78 patients with isolated cutaneous disease (P < 0.001). L. (V.) braziliensis (N = 3), L. (V.) guyanensis (N = 6), and L. (V.) peruviana (N = 3) were identified from urine. No healthy volunteer or patient with an alternate diagnosis had detectable kDNA in urine. Sensitivity of urine PCR is sub-optimal for diagnosis. On the basis of these preliminary data in a small number of patients, detectable kDNA in urine may identify less localized forms of infection and inform treatment decisions.
	PMID: 21460009 [PubMed - as supplied by publisher]
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6.	Am J Trop Med Hyg. 2011 Apr;84(4):551-5. Antihelminthic Therapy and Antimony in Cutaneous Leishmaniasis: A Randomized, Double-Blind, Placebo-Controlled Trial in Patients Co-Infected with Helminths and Leishmania braziliensis. Newlove T, Guimarães LH, Morgan DJ, Alcântara L, Glesby MJ, Carvalho EM, Machado PR. College of Medicine, University of Arizona, Tucson, Arizona; Serviço de Imunologia, Complexo Hospitalar Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College, New York; Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Bahia, Brazil. Abstract Abstract. Helminth infections influence the clinical response to certain diseases and are associated with delayed healing time of patients with cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. We conducted a randomized, double-blind, placebo-controlled clinical trial to examine the role of early versus deferred treatment of intestinal helminth infection on the clinical course of patients with CL treated with pentavalent antimony. (Clinicaltrials.gov number NCT00469495). A total of 90 patients were enrolled, 51.1% (N = 23) of control patients had persistent lesions at Day 90, compared with 62.2% (N = 28) in the treatment group (difference 11.1%, 95% confidence interval = -9.1-30.0%). There was no statistically significant difference in overall time to cure between groups, although there was a tendency for shorter cure times in the control group. This study shows that early introduction of antihelminthic therapy does not improve clinical outcome in patients co-infected with helminths and L. braziliensis.
	PMID: 21460008 [PubMed - in process]
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7.	Am J Trop Med Hyg. 2011 Apr;84(4):543-550. Who Is a Typical Patient with Visceral Leishmaniasis? Characteri zing the Demographic and Nutritional Profile of Patients in Brazil, East Africa, and South Asia. Harhay MO, Olliaro PL, Vaillant M, Chappuis F, Lima MA, Ritmeijer K, Costa CH, Costa DL, Rijal S, Sundar S, Balasegaram M. Graduate Group in Demography, Population Studies Center, University of Pennsylvania, Philadelphia, Pennsylvania; United Nations Children's Fund/United Nations Development Programme/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases (TDR), Geneva, Switzerland; Centre for Tropical Medicine, University of Oxford, Oxford, United Kingdom; Clinical Epidemiology and Public Health Unit, Center for Health Studies, Centre de Recherche Publique (CRP-Santé), Luxembourg; Médecins Sans Frontières, Operational Centre Geneva (MSF-OCG), Geneva, Switzerland; Division of International and Humanitarian Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland; Médecins Sans Frontières, Operational Centre Barcelona-Athens (MSF-OCBA), Barcelona, Spain; Médecins Sans Frontières, Operational Centre Amsterdam (MSF-OCA), Amsterdam, The Netherlands; Instituto de Doenças Tropicais Natan Portella, Teresina, Piauí, Brazil; Federal University of Piauí, Piauí, Brazil; Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Department of Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan, Nepal; Institute of Medical Sciences, Banaras Hindu University, Varanasi, India; Drugs for Neglected Diseases Initiative (DNDi), Geneva, Switzerland. Abstract Abstract. Drug-dosing recommendations for visceral leishmaniasis (VL) treatment are based on the patients' weight or age. A current lack of demographic and anthropometric data on patients hinders (1) the ability of health providers to properly prepare for patient management, (2) an informed drug procurement for disease control, and (3) the design of clinical trials and development of new drug therapies in the different endemic areas. We present information about the age, gender, weight, and height of 29,570 consecutive VL patients presenting to 20 locations in six geographic endemic regions of Brazil, East Africa, Nepal, and India between 1997 and 2009. Our compilation shows substantial heterogeneity in the types of patients seeking care for VL at the clinics within the different locations. This suggests that drug development, procurement, and perhaps even treatment protocols, such as the use of the potentially teratogenic drug miltefosine, may require distinct strategies in these geographic settings.
	PMID: 21460007 [PubMed - as supplied by publisher]
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8.	Am J Trop Med Hyg. 2011 Apr;84(4):539-42. Systemic Meglumine Antimoniate in Acute Cutaneous Leishmaniasis: Children versus Adults. Layegh P, Rahsepar S, Rahsepar AA. Research Center for Skin Diseases and Cutaneous Leishmaniasis, Qaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; Mashhad University of Medical Sciences, Mashhad, Iran. Abstract Abstract. Some studies showed that children have a lower response to systemic use of pentavalent antimoniate than adults. We aimed to evaluate the response rate to Glucantime therapy in children and compare it with adults. One hundred and twelve patients with acute cutaneous leishmaniais (ACL) were divided into two equal groups of adults (> 15 yrs) and children (≤ 15 yrs). They received meglumine antimoniate; 20 mg/kg/day for 20 days, their improvement rate was evaluated 20 and 45 days after treatment. Perprotocol analysis showed a significantly lower response in the children group 20 and 45 days after initiation of the treatment (P = 0.0001, 95% confidence interval [CI] = 0.190 [0.079-0.456]/P = 0.0051, 95% CI = 0.317 [0.140-0.717], respectively). Moreover, after intention-to-treat analysis, the same results were seen in the younger group 20 and 45 days after treatment (P = 0.0003, 95% CI = 0.228 [0.098-0.528]/P = 0.0132, 95% CI = 0.382 [0.177-0.825], respectively). According to our results, systemic Glucantime has lower efficacy in treating ACL in children than adults.
	PMID: 21460006 [PubMed - in process]
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9.	Exp Parasitol. 2011 Mar 30. [Epub ahead of print] Trypanocidal activity of peptidyl vinyl ester derivatives selective for inhibition of mammalian proteasome trypsin-like activity. Steverding D, Baldisserotto A, Wang X, Marastoni M. BioMedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom. Abstract Nine vinyl ester tripeptides selective for inhibition of mammalian proteasome trypsin-like activity were tested for in vitro activity against Trypanosoma brucei. Interestingly, two compounds showed trypanocidal activity in the low micromolar range without displaying cytotoxicity against human cells. However, the compounds did not inhibit the trypsin-like activity of the trypanosome proteasome although their effect correlates with inactivation of the chymotrypsin-like activity. This finding shows that the inhibitor sensitivities between mammalian and trypanosome proteasome are distinct. This difference may be exploited for rational anti-trypanosomal drug development. Copyright © 2011. Published by Elsevier Inc.
	PMID: 21458452 [PubMed - as supplied by publisher]
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10.	Biochem Biophys Res Commun. 2011 Mar 30. [Epub ahead of print] Leishmania express a functional Cdc20 homologue. Listovsky T, Brandeis M, Zilberstein D. Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000. Abstract Our knowledge concerning the mechanisms of cell cycle regulation in organisms belonging to the Trypanosometidae family is limited. L. donovani are parasitic protozoa that cause kalaazar, a fatal form of visceral leishmaniasis in humans. Here we provide evidence that the L. donovani genome contains a Cdc20 homologue. Cdc20 is a regulator of the Anaphase Promoting Complex/Cyclosome (APC/C) that mediates ubiqutin-dependent proteasomal degradation of key cell cycle regulators in eukaryotes. We show that L. donovani Cdc20 protein (LdCdc20p) can complement a lack of yeast Cdc20 protein in S. cerevisiae cells,validating the functionality of LdCdc20p. Furthermore, we demonstrate cyclic expression of LdCdc20p and that it contains an active RXXL destruction motif, a distinctive feature of proteins targeted for proteasomal degradation by APC/C. Finally, in line with the proteasome mediating LdCdc20p degradation, promastigotes exposed to proteasome inhibitor display elevated LdCdc20p levels. Taken together our data indicate that Leishmania regulate their cell cycle by ubiquitin-dependent proteasomaldegradation mediated by the APC/C. Copyright © 2011. Published by Elsevier Inc.
	PMID: 21458414 [PubMed - as supplied by publisher]
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