Tuesday, July 14, 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: Eur J Immunol. 2009 Jul 10. [Epub ahead of print]Click here to read

Complete protection against experimental visceral leishmaniasis with complete soluble antigen from attenuated Leishmania donovani promastigotes involves Th1-immunity and down-regulation of IL-10.

Bhaumik SK, Naskar K, De T.

Division of Infectious Disease and Immunology, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata, India.

Compared with cutaneous leishmaniasis, vaccination against visceral leishmaniasis has received limited attention. Most available drugs are toxic, and relapse after cure remains a chronic problem. Growing limitations in available chemotherapeutic strategies due to emerging resistant strains and lack of an effective vaccine strategy against visceral leishmaniasis deepens the crisis. Complete soluble antigen (CSA), from a beta1-4 galactosyltransferase expressing attenuated Leishmania donovani parasite, induced protection against subsequent challenge and during active infections. CSA immunization was effective against both pentavalent antimony sensitive and resistant strains of L. donovani. Majority ( approximately 85%) of the immunized animals showed sterile protection. Resolution of the disease required the presence of T cells, and the recovered animals remained immune to re-challenge. Control of the parasites was dependent on type 1 CD4(+) helper cells, which evolved in the presence of IL-12 and activated macrophages through the production of IFN-gamma. Immunity was adoptively transferable and was dependent on both CD4(+) and CD8(+) cells. CSA immunization led to enhanced IFN-gamma production, while suppressing the IL-10 production. However, CSA immunization did not abrogate IL-4 production. Our results accentuate the need to establish a favorable cellular immunity while intervening with the development of Th2 cells during leishmania infection.

PMID: 19593771 [PubMed - as supplied by publisher]

2: Scand J Infect Dis. 2009 Jul 10:1-6. [Epub ahead of print]Click here to read

Holiday souvenirs from the Mediterranean: Three instructive cases of visceral leishmaniasis.

Buonomano R, Brinkmann F, Leupin N, Boscacci R, Zimmermann A, Muller N, Fux CA.

From the Divisions of Infectious Diseases.

With expanding travel activities, visceral leishmaniasis increasingly occurs in non-endemic areas and affects immunocompetent individuals with no other risk factor than holidays at the Mediterranean coast. We report 3 instructive Swiss cases of visceral leishmaniasis presenting with fever of unknown origin and pancytopenia and review current diagnostic and therapeutic concepts.

PMID: 19593691 [PubMed - as supplied by publisher]

3: Parasitol Res. 2009 Jul 11. [Epub ahead of print]Click here to read

Evaluation of anti-leishmanial activity of selected Indian plants known to have antimicrobial properties.

Sharma U, Velpandian T, Sharma P, Singh S.

Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, 110 029, India.

The severe toxicity, exorbitant cost and the emerging resistance of Leishmania spp. against most of the currently used drugs led to the urgent need for exploiting our traditional Ayurvedic knowledge to treat visceral leishmaniasis. The aim of this study was to evaluate the in vitro anti-leishmanial activity of various extracts from ten traditionally used Indian medicinal plants. The methanolic extract from only two plants, Withania somnifera Dunal (ashwagandha) and Allium sativum Linn. (garlic), showed appreciable activity against Leishmania donovani. Further active compounds from these two plants were isolated and purified based on bioactivity-guided fractionation. HPLC-purified fraction A6 of ashwagandha and G3 of garlic showed consistently high activity with 50% inhibitory concentration (IC(50)) of 12.5 +/- 4 and 18.6 +/- 3 mug/ml against promastigotes whereas IC(50) of 9.5 +/- 3 and 13.5 +/- 2 mug/ml against amastigote form, respectively. The fraction A6 of ashwagandha was identified as withaferin A while fraction G3 of garlic is yet to be identified, and the work is in progress. Cytotoxic effects of the promising fractions and compounds were further evaluated in the murine macrophage (J774G8) model and were found to be safe. These compounds showed negligible cytotoxicity against J774G8 macrophages. The results indicate that fraction A6 of ashwagandha and fraction G3 of garlic might be potential sources of new anti-leishmanial compounds. The in vivo efficacy study and further optimization of these active compounds are in progress.

PMID: 19593584 [PubMed - as supplied by publisher]

4: J Immunol. 2009 Jul 10. [Epub ahead of print]Click here to read

Intracellular Replication-Deficient Leishmania donovani Induces Long Lasting Protective Immunity against Visceral Leishmaniasis.

Selvapandiyan A, Dey R, Nylen S, Duncan R, Sacks D, Nakhasi HL.

*Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, 20892.

No vaccine is currently available for visceral leishmaniasis (VL) caused by Leishmania donovani. This study addresses whether a live attenuated centrin gene-deleted L. donovani (LdCen1(-/-)) parasite can persist and be both safe and protective in animals. LdCen1(-/-) has a defect in amastigote replication both in vitro and ex vivo in human macrophages. Safety was shown by the lack of parasites in spleen and liver in susceptible BALB/c mice, immune compromised SCID mice, and human VL model hamsters 10 wk after infection. Mice immunized with LdCen1(-/-) showed early clearance of virulent parasite challenge not seen in mice immunized with heat killed parasites. Upon virulent challenge, the immunized mice displayed in the CD4(+) T cell population a significant increase of single and multiple cytokine (IFN-gamma, IL-2, and TNF) producing cells and IFN-gamma/IL10 ratio. Immunized mice also showed increased IgG2a immunoglobulins and NO production in macrophages. These features indicated a protective Th1-type immune response. The Th1 response correlated with a significantly reduced parasite burden in the spleen and no parasites in the liver compared with naive mice 10 wk post challenge. Protection was observed, when challenged even after 16 wk post immunization, signifying a sustained immunity. Protection by immunization with attenuated parasites was also seen in hamsters. Immunization with LdCen1(-/-) also cross-protected mice against infection with L. braziliensis that causes mucocutaneous leishmaniasis. Results indicate that LdCen1(-/-) can be a safe and effective vaccine candidate against VL as well as mucocutaneous leishmaniasis causing parasites.

PMID: 19592661 [PubMed - as supplied by publisher]

5: Parasitol Int. 2009 Jul 7. [Epub ahead of print]Click here to read

In vivo induction of the autophagic machinery in human bone marrow cells during Leishmania donovani complex infection.

Mitroulis I, Kourtzelis I, Papadopoulos VP, Mimidis K, Speletas M, Ritis K.

First Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece.

Autophagy is a homeostatic process promoting cell survival in periods of stress. The induction of the autophagic machinery has also been implicated in both innate and adaptive immunity. Leishmania donovani, which is the causative pathogen of visceral leishmaniasis, is an intracellular parasite that invades and multiplies in bone marrow macrophages. We describe the induction of host cell autophagic machinery during acute natural bone marrow infection by L. donovani complex, detected by LC3B immunoblot. The successful treatment with liposomal amphotericin B resulted in the resolution of this phenomenon. Even though the role of autophagy in parasite biology has been previously studied, our findings show for the first time the in vivomicron host cell LC3B conversion as a marker of the induction of the autophagic machinery during infection with Leishmania parasite in real time conditions.

PMID: 19591960 [PubMed - as supplied by publisher]

6: J Dermatol. 2009 Apr;36(4):209-12.Click here to read OMIM (calculated), LinkOut

Evaluation of insulin resistance in obese women with and without acanthosis nigricans.

Sadeghian G, Ziaie H, Amini M, Ali Nilfroushzadeh M.

Skin Disease and Leishmaniasis Research Center, Isfahan, Iran. Sadeghian@sdlrc.mui.ac.ir

Acanthosis nigricans is characterized by hyperpigmented velvety plaques of body folds and neck. Insulin could be a responsible factor in the pathogenesis of this condition and hyperinsulinemia: a consequence of insulin resistance stimulates the formation of these characteristic plaques. In this study, insulin resistance was compared in obese women with and without acanthosis nigricans. This was a cross-sectional study. Sixty-six obese women (32 patients with acanthosis nigricans and 34 patients without acanthosis nigricans) were selected randomly. Levels of fasting serum insulin and fasting blood glucose were measured in both groups and insulin resistance was determined using homeostasis model assessment. Glucose tolerance test also was performed for all of participants. Five (15.6%) patients with acanthosis nigricans and no (0%) patient without acanthosis nigricans had insulin resistance (P < 0.05). Six (18.7%) patients with acanthosis nigricans and one (2.9%) patient without acanthosis nigricans had impaired glucose tolerance test (P < 0.05). The mean levels of fasting serum insulin were 15.7 +/- 8.7 and 12.2 +/- 4.1 microm/mL (P < 0.05) and the mean values of insulin resistance index were 3.5 +/- 1.9 and 2.6 +/- 0.9 microm/mL between patients with and without acanthosis nigricans, respectively (P < 0.05). In Iranian obese women, acanthosis nigricans is a marker of insulin resistance.

PMID: 19348659 [PubMed - indexed for MEDLINE]

7: J Biol Chem. 2009 Jun 5;284(23):15353-7. Epub 2009 Feb 5.Click here to read LinkOut

Catalytic domain architecture of metzincin metalloproteases.

Gomis-Rüth FX.

Proteolysis Lab, Molecular Biology Institute of Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona Science Park, Helix Building, c/Baldiri Reixac, 15-21, E-08028 Barcelona, Spain. fxgr@ibmb.csic.es

Metalloproteases cleave proteins and peptides, and deregulation of their function leads to pathology. An understanding of their structure and mechanisms of action is necessary to the development of strategies for their regulation. Among metallopeptidases are the metzincins, which are mostly multidomain proteins with approximately 130-260-residue globular catalytic domains showing a common core architecture characterized by a long zinc-binding consensus motif, HEXXHXXGXX(H/D), and a methionine-containing Met-turn. Metzincins participate in unspecific protein degradation such as digestion of intake proteins and tissue development, maintenance, and remodeling, but they are also involved in highly specific cleavage events to activate or inactivate themselves or other (pro)enzymes and bioactive peptides. Metzincins are subdivided into families, and seven such families have been analyzed at the structural level: the astacins, ADAMs/adamalysins/reprolysins, serralysins, matrix metalloproteinases, snapalysins, leishmanolysins, and pappalysins. These families are reviewed from a structural point of view.

PMID: 19201757 [PubMed - indexed for MEDLINE]

PMCID: PMC2708831 [Available on 2010/06/05]

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