Friday, October 16, 2009

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 -7 of 7

1: Med Parazitol (Mosk). 2009 Jul-Sep;(3):45-7.

[The possibility of antibiotic therapy in leishmaniasis]

[Article in Russian]

[No authors listed]

The authors describe cases of leishmaniasis for which claforan (cefotaxime) has been used, showing an obvious improvement in visceral leishmaniasis in children and a full recovery in cutaneous leishmaniasis in adults.

PMID: 19830916 [PubMed - in process]

2: Planta Med. 2009 Oct 14. [Epub ahead of print]

Anti-Leishmanial Lindenane Sesquiterpenes from Hedyosmum angustifolium.

Acebey L, Jullian V, Sereno D, Chevalley S, Estevez Y, Moulis C, Beck S, Valentin A, Gimenez A, Sauvain M.

Instituto de Investigaciones Fármaco Bioquímicas, Facultad de Ciencias Farmacéuticasy Bioquímicas, Universidad Mayor de San Andrés, La Paz, Bolivia.

The aim of this work is the isolation of anti-leishmanial compounds from the ethyl acetate extracts of the bark of HEDYOSMUM ANGUSTIFOLIUM. We have successfully isolated and characterized five sesquiterpenes: one new compound (oxyonoseriolide, 1), one compound isolated for the first time from a natural source (hedyosmone, 2), and three known sesquiterpenes (onoseriolide, 3; chloranthalactone A, 4; and spathulenol, 5) that had not been previously isolated from H. ANGUSTIFOLIUM. The biological activities of 1- 5 showed that onoseriolide ( 3) was the most active compound against axenic amastigotes from LEISHMANIA AMAZONENSIS and L. INFANTUM. Moreover, it was still active on the intramacrophagic amastigotes of L. INFANTUM. The isolated compounds have also been tested on PLASMODIUM FALCIPARUM and against various mammalian cell lines. © Georg Thieme Verlag KG Stuttgart · New York.

PMID: 19830657 [PubMed - as supplied by publisher]

3: J Med Case Reports. 2009 Jun 25;3:7265.

Progressive visceral leishmaniasis misdiagnosed as cirrhosis of the liver: a case report.

Giannitrapani L, Soresi M, La Spada E, Tripodo C, Montalto G.

INTRODUCTION: Visceral leishmaniasis is a potentially life-threatening infectious disease which is caused by parasites of the genus Leishmania and characterized in most cases by the presence of fever as well as signs and symptoms similar to those found in liver cirrhosis. CASE PRESENTATION: In this case report we describe the history of a 50-year-old Caucasian man incorrectly diagnosed as having hepatitis C virus-associated liver cirrhosis, with a massive weight loss of around 100 kg during the previous 2 years. However, suspecting a lymphoproliferative disorder, we were able to make a correct diagnosis of visceral leishmaniasis by bone marrow examination. After a course of therapy with Liposomal Amphotericin-B the patient recovered and now, 20 months post-treatment, he is well and has regained a good part of the lost weight. CONCLUSIONS: This case taught us that patients with massive splenomegaly, even with a diagnosis of liver cirrhosis, should be investigated for infectious or lymphoproliferative diseases.

PMID: 19830157 [PubMed - in process]

4: J Biol Chem. 2009 Oct 14. [Epub ahead of print]

Chemical validation of trypanothione synthetase: a potential drug target for human trypanosomiasis.

Torrie LS, Wyllie S, Spinks D, Oza SL, Thompson S, Harrison JR, Gilbert IH, Wyatt PG, Fairlamb AH, Frearson JA.

University of Dundee, United Kingdom.

In the search for new therapeutics for the treatment of Human African Trypanosomiasis many potential drug targets in Trypanosoma brucei have been validated by genetic means, but very few have been chemically validated. Trypanothione synthetase (TryS; EC 6.3.1.9; spermidine / glutathionylspermidine : glutathione ligase (ADP-forming)) is one such target. To identify novel inhibitors of T. brucei TryS we developed an in vitro enzyme assay, which was amenable to high-throughput screening. The subsequent screen of a diverse compound library resulted in the identification of three novel series of TryS inhibitors. Further chemical exploration resulted in leads with nanomolar potency, which displayed mixed, uncompetitive and allosteric-type inhibition with respect to spermidine, ATP and glutathione, respectively. Representatives of all three series inhibited growth of bloodstream T. brucei in vitro . Exposure to one of our lead compounds (DDD86243; 2 x EC( 50 ) for 72 h), decreased intracellular trypanothione levels to <10% of wild-type. In addition, there was a corresponding 5-fold increase in the precursor metabolite, glutathione, providing strong evidence that DDD86243 was acting on target to inhibit TryS. This was confirmed with wild-type, TryS single knockout and TryS over-expressing cell lines showing expected changes in potency to DDD86243. Taken together, these data provide initial chemical validation of TryS as a drug target in T. brucei .

PMID: 19828449 [PubMed - as supplied by publisher]

5: J Infect Dis. 2009 Oct 14. [Epub ahead of print]

Expression and Role of CXCL10 during the Encephalitic Stage of Experimental and Clinical African Trypanosomiasis.

Amin DN, Rottenberg ME, Thomsen AR, Mumba D, Fenger C, Kristensson K, Büscher P, Finsen B, Masocha W.

Department of Neuroscience and 2Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden; 3 Department of International Health, Immunology & Microbiology, University of Copenhagen, Copenhagen, 4Medical Biotechnology Center, Institute of Medical Biology, University of Southern Denmark, Odense, Denmark; 5Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo; 6Institute of Tropical Medicine, Department of Parasitology, Antwerp, Belgium; and 7Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Safat, Kuwait.

Background. Human African trypanosomiasis, caused by Trypanosoma brucei, involves an early hemolymphatic stage followed by a late encephalitic stage. Methods. We studied the expression of chemokines with use of microarray and enzyme-linked immunosorbent assay in T. brucei brucei-infected mice and in patients with human African trypanosomiasis and examined their role in controlling brain accumulation of T cells and parasites. Results. The messenger RNAs (mRNAs) encoding CXCR3 ligands CXCL9 and CXCL10 demonstrated the greatest increases among chemokines in brain specimens of infected mice, as determined by microarray. CXCL9 and CXCL10 mRNA accumulation was interferon (IFN)-gamma-dependent. Expression of CXCL10 was predominantly observed in astrocytes. Weight loss was registered in wild-type but not in CXCL10(-/-) and CXCR3(-/-) infected mice. Infected CXCL10(-/-) or CXCR3(-/-) mice demonstrated reduced accumulation of trypanosomes and T cells in the brain parenchyma but similar parasitemia levels, compared with wild-type mice. CXCL10 and IFN-gamma levels were increased in the cerebrospinal fluid of patients with late stage but not early stage human African trypanosomiasis. Levels of CXCL10 in patients with late stage human African trypanosomiasis were associated with somnolence, low body weight, and trypanosomes in the cerebrospinal fluid. Conclusion. IFN-gamma-dependent CXCL10 is critical for accumulation of T cells and trypanosomes in the brain during experimental African trypanosomiasis. Data suggest CXCL10 as a candidate marker for late stage human African trypanosomiasis .

PMID: 19827943 [PubMed - as supplied by publisher]

6: Appl Physiol Nutr Metab. 2009 Aug;34(4):659-65.Click here to read LinkOut

Preinfection aerobic treadmill training improves resistance against Trypanosoma cruzi infection in mice.

Schebeleski-Soares C, Occhi-Soares RC, Franzói-de-Moraes SM, de Oliveira Dalálio MM, Almeida FN, de Ornelas Toledo MJ, de Araújo SM.

Department of Physiological Sciences, State University of Maringa, Avenida Colombo, Maringa, Brazil. schebeleski@ibest.com.br

Exercise performed before infections has been linked to improvement of the immune response against infections. The purpose of this study was to evaluate the influence of preinfection moderate-intensity treadmill training on acute Trypanosoma cruzi infection in mice. Ninety-nine female BALB/c mice were divided into 4 groups, as follows: training + infection (T+I) (n = 41); no training + infection (NT+I) (n = 38); training + no infection (T+NI) (n = 10); and no training + no infection (NT+NI) (n = 10). The exercise program for trained groups was carried out on a motorized treadmill for 8 weeks. Infected groups were inoculated with the Y strain of T. cruzi. Infectivity, prepatent period, patent period, parasitemia peak, mortality, survival time, weight, food intake, tumor necrosis factor-alpha serum levels, and peritoneal macrophage hydrogen peroxide production were evaluated. We found that preinfection training induced statistically significant reductions in parasitemia peak (p < 0.03) and weight loss (p < 0.04). However, no statistically significant differences were found for the other parameters evaluated when trained and nontrained infected groups were compared. We conclude that preinfection aerobic training induces some improvement in the immune response to T. cruzi infection in female BALB/c mice.

PMID: 19767801 [PubMed - indexed for MEDLINE]

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7: PLoS Pathog. 2009 Jul;5(7):e1000514. Epub 2009 Jul 17.Click here to read Click here to read References for this PMC Article, Free in PMC, LinkOut

NFATc1 mediates Toll-like receptor-independent innate immune responses during Trypanosoma cruzi infection.

Kayama H, Koga R, Atarashi K, Okuyama M, Kimura T, Mak TW, Uematsu S, Akira S, Takayanagi H, Honda K, Yamamoto M, Takeda K.

Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.

Host defense against the intracellular protozoan parasite Trypanosoma cruzi depends on Toll-like receptor (TLR)-dependent innate immune responses. Recent studies also suggest the presence of TLR-independent responses to several microorganisms, such as viruses, bacteria, and fungi. However, the TLR-independent responses to protozoa remain unclear. Here, we demonstrate a novel TLR-independent innate response pathway to T. cruzi. Myd88(-/-)Trif(-/-) mice lacking TLR signaling showed normal T. cruzi-induced Th1 responses and maturation of dendritic cells (DCs), despite high sensitivity to the infection. IFN-gamma was normally induced in T. cruzi-infected Myd88(-/-)Trif(-/-) innate immune cells, and further was responsible for the TLR-independent Th1 responses and DC maturation after T. cruzi infection. T. cruzi infection induced elevation of the intracellular Ca(2+) level. Furthermore, T. cruzi-induced IFN-gamma expression was blocked by inhibition of Ca(2+) signaling. NFATc1, which plays a pivotal role in Ca(2+) signaling in lymphocytes, was activated in T. cruzi-infected Myd88(-/-)Trif(-/-) innate immune cells. T. cruzi-infected Nfatc1(-/-) fetal liver DCs were impaired in IFN-gamma production and DC maturation. These results demonstrate that NFATc1 mediates TLR-independent innate immune responses in T. cruzi infection.

PMID: 19609356 [PubMed - indexed for MEDLINE]

PMCID: PMC2704961

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