What's new for 'Trypanosomatids' in PubMed

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Sent on Friday, 2010 Jun 04
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 11

1.	AAPS PharmSciTech. 2010 Jun 3. [Epub ahead of print] Study of In Vitro Drug Release and Percutaneous Absorption of Fluconazole from Topical Dosage Forms. Salerno C, Carlucci AM, Bregni C. Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Junin 954, 1113, Buenos Aires, Argentina, salernoclaudia3@gmail.com. Abstract The present study aimed to evaluate different dosage forms, emulsions, emulgels, lipogels, and thickened microemulsion-based hydrogel, as fluconazole topical delivery systems with the purpose of determining a formulation with the capacity to deliver the whole active compound and maintain it within the skin so as to be considered a useful formulation either for topical mycosis treatment or as adjuvant in a combined therapy for Cutaneous Leishmaniasis. Propylene glycol and diethyleneglycol monoethyl ether were used for each dosage form as solvent for the drug and also as penetration enhancers. In vitro drug release after application of a clinically relevant dose of each formulation was evaluated and then microemulsions and lipogels were selected for the in vitro penetration and permeation study. Membranes of mixed cellulose esters and full-thickness pig ear skin were used for the in vitro studies. Candida albicans was used to test antifungal activity. A microemulsion containing diethyleneglycol monoethyl ether was found to be the optimum formulation as it was able to deliver the whole contained dose and enhance its skin penetration. Also this microemulsion showed the best performance in the antifungal activity test compared with the one containing propylene glycol. These results are according to previous reports of the advantages of microemulsions for topical administration and they are very promising for further clinical evaluation.
	PMID: 20521179 [PubMed - as supplied by publisher]

2.	PLoS Negl Trop Dis. 2010 May 25;4(5):e720. NECT Is Next: Implementing the New Drug Combination Therapy for Trypanosoma brucei gambiense Sleeping Sickness. Yun O, Priotto G, Tong J, Flevaud L, Chappuis F. Médecins Sans Frontières/Doctors Without Borders, New York, New York, United States of America.
	PMID: 20520803 [PubMed - in process]

3.	Am J Trop Med Hyg. 2010 Jun;82(6):983-90. Identification of stage biomarkers for human african trypanosomiasis. Amin DN, Ngoyi DM, Nhkwachi GM, Palomba M, Rottenberg M, Büscher P, Kristensson K, Masocha W. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Institut National De Recherche Biomédicale, Kinshasa, Democratic Republic of Congo; Centre For Ticks and Tick-Borne Diseases, Lilongwe, Malawi, Section of Anatomy and Histology, Faculty of Medicine, University of Verona, Verona, Italy; Institute of Tropical Medicine, Department of Parasitology, Antwerp, Belgium; Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait. Abstract Human African trypanosomiasis (HAT), caused by infection with sub-species of Trypanosoma brucei (T. b.), manifests as a hemolymphatic stage followed by an encephalitic stage. The distinction of the two stages needs improvement as drugs used for the late stage are highly toxic. Transcripts encoding 16 secreted proteins differentially expressed in the brains of mice at late stage T. b. brucei infection when the early stage drug suramin is no longer effective and different to immunoglobulins, chemokines, and cytokines, were selected by microarray analysis. Lipocalin 2 and secretory leukocyte peptidase inhibitor (SLPI) mRNA showed the highest differential expression in mice. These transcripts were also upregulated in brains from infected rats. Lipocalin 2 was increased in cerebrospinal fluid (CSF) from rats during late stage T. b. brucei infection. Protein levels of lipocalin 2, SLPI, and the chemokine CXCL10 were found increased in CSF from Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense late stage HAT compared to early stage.
	PMID: 20519589 [PubMed - in process]

4.	Am J Trop Med Hyg. 2010 Jun;82(6):981-2. Novel biomarkers for late-stage human african trypanosomiasis--the search goes on. Kennedy PG. Department of Neurology, Division of Clinical Neurosciences, Institute of Neurological Sciences, Southern General Hospital, Glasgow University, Glasgow, Sc otland.
	PMID: 20519588 [PubMed - in process]

5.	J Antimicrob Chemother. 2010 Jun 2. [Epub ahead of print] Molecular docking, structure-activity relationship and biological evaluation of the anticancer drug monastrol as a pteridine reductase inhibitor in a clinical isolate of Leishmania donovani. Kaur J, Sundar S, Singh N. Drug Target Discovery & Development Division, Central Drug Research Institute, Chattar Manzil Palace, PO Box No. 173, Lucknow-226001, CSIR, India. Abstract Objectives Using the pteridine reductase (PTR1) enzyme of Leishmania as the target, the objective of our study was to find a drug candidate that can enter the clinical development process after being evaluated for safety and efficacy in animals. Methods Monastrol (R) and (S) enantiomers were docked using the QUANTUM program into the active site of a Leishmania donovani PTR1 (LdPTR1) homology model. A structure-activity relationship based on a homology model of a recombinant enzyme was substantiated by a recombinant enzyme inhibition assay. We adapted an L. donovani (transfected with green fluorescent protein) intramacrophage amastigote screening assay as a cellular model for leishmaniasis. Furthermore, since the clinicopathological features and immunopathological mechanisms of visceral leishmaniasis (VL) in a hamster model are remarkably similar to those of human disease, systemic infection of hamsters with L. donovani was utilized to collect in vivo data for monastrol. Results Both monastrol (R) and (S) enantiomers fit well in the ligand-binding pocket of LdPTR1. Monastrol exhibits a K(i) value of 0.428 microM in the recombinant enzyme inhibition assay. We confirm monastrol as a potent inhibitor of PTR1 in Leishmania; it inhibits proliferation of amastigotes with an IC(50) (50% inhibitory concentration) of 10 microM in macrophage cultures infected with an L. donovani clinical isolate, with no host cytotoxicity. We also show that in experimental animals, oral administration of a 5 mg/kg dose of monastrol on two alternate days inhibits 50% of parasite growth, giving therapeutic backing to the use of monastrol as a potent antileishmanial in human VL cases. Conclusions To our knowledge, this is the first report presenting monastrol as a potent oral antileishmanial.
	PMID: 20519355 [PubMed - as supplied by publisher]

6.	Vector Borne Zoonotic Dis. 2010 Jun 2. [Epub ahead of print] Effects of Ivermectin on Blood-Feeding Phlebotomus papatasi, and the Promastigote Stage of Leishmania major. Hanafi HA, Szumlas DE, Fryauff DJ, El-Hossary SS, Singer GA, Osman SG, Watany N, Furman BD, Hoel DF. 1 Vector Biology Research Program , U.S. Naval Medical Research Unit No. 3, Cairo, Egypt . Abstract Abstract Ivermectin (IVM) is a chemically modified macrocyclic lactone of Streptomyces avermitilis that acts as a potent neurotoxin against many nematodes and arthropods. Little is known of IVM's effect against either blood-feeding Phlebotomus sand flies, or the infective promastigote stage of Leishmania transmitted by these flies. We injected hamsters subcutaneously with two standard IVM treatments (200 and 400 mug/kg body weight) and allowed cohorts of Leishmania major-infected Phlebotomus papatasi to blood-feed on these animals at various posttreatment time points (4 h, 1, 2, 6, and 10 days). Infected and uninfected sand flies that bit treated and untreated hamsters served as controls. Serum levels of IVM in low- and high-dose-treated hamsters were determined at the five time points. Sand fly mortality following blood feeding was recorded at 24-h intervals and, in relation to IVM treatment, was time and dose dependent. Mortality was most rapid and greatest among infected flies that fed nearest to time of dosing. Mean survival of infected sand flies after feeding on untreated hamsters was 11.5 days, whereas that of infected sand flies that fed 4 h, 1 day, or 2 days posttreatment on high-dose-treated hamsters (400 mug/kg) was 1.6, 2.1, and 2.7 days, respectively. Infected and uninfected sand flies that blood fed 6 days following low-dose IVM treatment (200 mug/kg) still experienced significantly greater mortality (p < 0.02) than controls. Promastigotes dissected out of surviving flies that fed on IVM-treated hamsters showed typical motility and survival. Moreover, 21.7% of IVM-treated hamsters developed lesions after being fed upon by infected sand flies. L. major promastigotes appeared to be tolerant to ng/mL blood levels of IVM that caused significant mortality for up to 10 days posttreatment in blood-feeding P. papatasi.
	PMID: 20518644 [PubMed - as supplied by publisher]

7.	Scand J Immunol. 2010 Mar;71(3):220-5. Autoantibodies to neurotrophic receptors TrkA, TrkB and TrkC in patients with acute Chagas' disease. Lu B, Luquetti AO, Rassi A, PereiraPerrin M. Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA. Abstract Neurotrophic receptors TrkA and TrkC double up as receptors that Trypanosoma cruzi uses to invade cells and as autoantigen in T. cruzi-infected individuals (with Chagas' disease). Consequently, autoantibodies against TrkA and TrkC (ATA) potently block T. cruzi invasion in vitro and in ATA-immunized mice. Thus, ATA could keep T. cruzi invasion in check in Chagas' disease. However, ATA has been examined only in patients with chronic Chagas' disease. To determine whether ATA potentially participate in the early stage of infection, we analysed the sera of 15 patients with acute Chagas' disease, 4-66 years of age. We find that all sera contain high antibody titres to TrkA, TrkB and TrkC, but not to other growth factor receptors, indicating that ATA are produced relatively soon after T. cruzi infection by an age-independent process. One individual, who acquired the disease after an accidental laboratory infection, converted to Trk-antibody (Ab)-seronegative when progressing to the chronic phase. ATA from acute patients were of low avidity (K(0) <24.8 x 10(-8) m) and of IgM and IgA isotypes. In contrast, ATA from chronic patients were of high avidity (K(o) = 1.4 to 4.5 x 10(-8) m) and of the IgG2 isotype. Therefore, ATA underwent affinity maturation and class switch when patients progressed from acute to chronic disease. Thus, it may be that Trk autoimmunity, which starts in the acute Chagas' disease, plays a role in attenuating parasitemia and tissue parasitism that characterizes the acute/chronic phase transition of Chagas' disease.
	PMID: 20415787 [PubMed - indexed for MEDLINE]
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8.	Neth J Med. 2010 Jan;68(1):41-4. A family with skin lesions. Ozaras R, Polat E, Aygun G, Yemisen M, Mete B, Goksugur N, Tabak F. Department of Infectious Diseases, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey. rozaras@yahoo.com Free Article
	PMID: 20103823 [PubMed - indexed for MEDLINE]
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9.	Medicina (B Aires). 2009;69(5):585-8. [Carlos Chagas: centenary of a brilliant work] [Article in Spanish] Manigot DA.
	PMID: 19897450 [PubMed - indexed for MEDLINE]
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10.	Medicina (B Aires). 2009;69(5):529-35. [Maternal-fetal transmission of Trypanosoma cruzi in Argentina] [Article in Spanish] de Rissio AM, Scollo K, Cardoni RL. Instituto Nacional de Parasitología Fatala Chaben (INP)-ANLIS Malbrán, Buenos Aires. Abstract In the neonates born to T. cruzi infected mothers, the diagnosis of the congenital transmission relays on the detection of the parasites and/or the specific antibodies non-transferred by their mothers, in the absence of blood transfusion and vectorial transmission. In the early stage, approximately until the 7th month of life, when maternal immunoglobulins could be present, the diagnosis depends on the detection of the parasite. Then, in the late stage, from the 8th month, the detection of specific antibodies by at least 2 of 3 serological tests confirms the infection in the neonates. The diagnostic follow up of the children born to a group of sero-reactive pregnant women was carried out in the INP. The 11% of the mothers (29 out of 267) transmitted the infection to their children. The neonates of 20 of these mothers were diagnosed in the early stage, 14 and 6 in one or two controls, respectively. In the 9 remaining mothers the children were diagnosed in the late stage of the infection, mainly serologicaly. Our analisis of previously published reports stressed that the maternal-fetal transmission rate depends on the time of diagnostic follow up of the child. In this reports, mean values of mother to child transmission reported was 2% and 9% when the diagnosis of the neonates born to sero-reactive mothers was carried out only in the early stage or in the early and also the late stage, respectively.
	PMID: 19897438 [PubMed - indexed for MEDLINE]
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