[Leish-l] Fwd: Articles found by RefScout 6/2007

[Jeffrey Shaw]

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Date: Wed, 7 Feb 2007 01:07:19
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(25 articles match this request)

PMID: 17142057<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=17142057>
TITLE: Molecular cloning and biochemical characterization of
*Leishmania*donovani serine
hydroxymethyltransferase.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17142057>
AUTHORS: Rit Vatsyayan, Uma Roy
AFFILIATION: Biochemistry Division, Central Drug Research Institute, Lucknow
226001, India.
REFERENCE: Protein Expr Purif 2007 Apr 52(2):433-40
Serine hydroxymethyltransferase (SHMT) catalyzes the inter conversion of
serine and tetrahydrofolate (H(4)-folate) to form glycine and 5,10-
methylene H(4)-folate and generates one-carbon fragments for the synthesis
of nucleotides, methionine, thymidylate, choline, etc. In spite of being an
indispensable enzyme of the thymidylate cycle, SHMT in *Leishmania* donovani
remains uncharacterized. The study of L. donovani SHMT (ldSHMT) becomes
important as this gene is preferentially expressed in the amastigote stage
of parasite, which resides in human macrophages . Here we report cloning,
expression and purification of a catalytically active ldSHMT. The
homogeneity of recombinant protein was analyzed by denaturing gel
electrophoresis and protein was found to be 95% pure having yield of 1mg/l.
The recombinant protein is a tetramer of 216kDa as evidenced by gel
filtration chromatography and uses serine and tetrahydrofolate as substrates
with Km of 1.6 and 2.4mM, respectively. Further biochemical studies revealed
that pH optimum of ldSHMT is 7.8 and enzyme is thermally stable up to 45
degrees C. ldSHMT was found sensitive towards denaturants as manifested by
loss of enzyme activity at the concentration of 1M urea or 0.25M guanidine
hydrochloride. This is the first report of purification and characterization
of recombinant SHMT from any protozoan source. Studies on recombinant ldSHMT
will help in evaluating this enzyme as potential drug target.


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PMID: 16786361<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=16786361>
TITLE: A new view on cutaneous dendritic cell subsets in experimental
leishmaniasis.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16786361>
AUTHORS: Uwe Ritter, Anke Osterloh
AFFILIATION: Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht
Strasse 74, 20359, Hamburg, Germany, ritter at bni-hamburg.de.
REFERENCE: Med Microbiol Immunol (Berl) 2007 Mar 196(1):51-9
Because of their anatomical distribution epidermal Langerhans cells (LCs )
are discussed to be crucial for antigen uptake and subsequent presentation
to naïve T cells in skin-draining lymph nodes. The use of LC-specific
markers like Langerin or knock-in mice expressing green fluorescent protein
under the control of the Langerin promotor now facilitates the dissection of
LCs from other dendritic cell (DC) subsets . Surprisingly, current data
indicate that LCs are not generally involved in the induction of cellular
immune responses. Moreover, the widely accepted paradigm postulating that
LCs in principle act as T cell activators is contested by recent
publications. Consequently, the biological role of LCs, in particular in
cutaneous immune responses, needs to be revisited. The experimental model of
leishmaniasis represents a suitable model to study the origin of an
antigen-specific T cell response in mice. With this model the transport and
presentation of skin derived *Leishmania* (L.) major antigens can be
monitored in vivo . Furthermore, the quality of T cell-DC interactions can
be determined. Considering recent progress in LC research we propose a novel
concept of LCs in T cell meditated immunity against L. major parasites.


PMID: 17266739<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=17266739>
TITLE: Monocyte cytokine and costimulatory molecule expression in patients
infected with *Leishmania*
mexicana.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17266739>
AUTHORS: G Carrada, C Cañeda, N Salaiza, J Delgado, A Ruiz, B Sanchez, L
GutiÃ(c)rrez-Kobeh, M Aguirre, I Becker
AFFILIATION: Departamento de Medicina Experimental, Facultad de Medicina,
Universidad Nacional Autónoma de MÃ(c)xico, MÃ(c)xico D.F., MÃ(c)xico.
REFERENCE: Parasite Immunol 2007 Mar 29(3):117-26
*Leishmania* mexicana causes localized and diffuse cutaneous leishmaniasis .
Patients with localized cutaneous leishmaniasis (LCL) develop a benign
disease, whereas patients with diffuse cutaneous leishmaniasis (DCL) suffer
from a progressive disease associated with anergy of the cellular response
towards *Leishmania* antigens. We evaluated the production of the
interleukins (IL) IL-12, IL-15, IL-18 and tumour necrosis factor- alpha
(TNF-alpha) and the expression of the costimulatory molecules CD40 , B7-1
and B7-2 in monocytes from LCL and DCL patients, stimulated in vitro with *
Leishmania* mexicana lipophosphoglycan (LPG) for 18 h. LCL monocytes
significantly increased TNF-alpha, IL-15 and IL-18 production , and this
increase was associated with reduced amounts of IL-12. DCL monocytes
produced no IL-15 or IL-18 and showed a decreasing tendency of TNF-alpha and
IL-12 production as the severity of the disease increased . No difference
was observed in the expression of CD40 and B7-1 between both groups of
patients, yet B7-2 expression was significantly augmented in DCL patients.
It remains to be established if this elevated B7-2 expression in DCL
patients is cause or consequence of the Th2-type immune response that
characterizes these patients. These data suggest that the diminished ability
of the monocytes from DCL patients to produce cell-activating innate
proinflammatory cytokines when stimulated with LPG is a possible cause for
disease progression.


PMID: 17129395<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=17129395>
TITLE: Specific cpb copies within the *Leishmania* donovani complex:
evolutionary interpretations and potential clinical implications in
humans.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17129395>
AUTHORS: M Hide, R Bras-Gonçalves, A L Bañuls
AFFILIATION: GÃ(c)nÃ(c)tique et Evolution des Maladies Infectieuses, IRD/CNRS
(UMR 2724), F-34394, France.
REFERENCE: Parasitology 2007 Mar 134(Pt 3):379-89
*Leishmania* infantum and *Leishmania* donovani both pertain to the L. (L.)
donovani complex and are responsible for visceral leishmaniasis. To explore
the L. donovani complex, we focused our study on cysteine protease B (cpb)
and especially on 2 cpb copies: cpbE and cpbF. We selected cpb genes because
of their phylogenetic interest and host- parasite interaction involvement.
Sequencing these 2 copies revealed (i ) that cpbE is specific to L. infantum
and cpbF is specific to L. donovani and (ii) that these 2 copies are
different in length and sequence.Nucleotide sequence data reported in this
paper are available in the GenBank database under Accession numbers AY896776
AY896777, AY896778, AY896779, AY896780, AY896781, AY896782, AY896783,
AY896784, AY896785, AY896786, AY896787, AY896788, AY896789, AY896790,
AY896791. Phylogenetic analysis and protein predictions were carried out in
order to compare these copies (i) with other trypanosomatid cpb, especially
L . mexicana, and (ii) within the L. donovani complex. Our results revealed
patterns specific to the L. donovani complex such as the COOH- terminal
extension, potential epitopes and N-glycosylation sites. Moreover,
phylogenetic analysis revealed different levels of polymorphism between L.
infantum and L. donovani and confirmed the ancestral status of the latter.
L. infantum has a shorter sequence and a deleted sequence responsible for
modifications in protein conformation and catalytic triad. Considering the
clinical aspect, L. infantum dermotropic strains appeared more polymorphic
than L. infantum viscerotropic strains.


PMID: 17262718<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=17262718>
TITLE: Selective Expression of the V beta 14 T Cell Receptor on
*Leishmania*guyanensis-Specific CD8+ T Cells during Human
Infection.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17262718>
AUTHORS: Amina Kariminia, Eliane Bourreau, Catherine Ronet, Pierre Couppie,
Dominique Sainte-Marie, Fabienne Tacchini-Cottier, Pascal Launois
AFFILIATION: Immunologie des Leishmanioses, Institut Pasteur de la Guyane,
Cayenne, French Guyana. pascal.launois at unil.ch.
REFERENCE: J Infect Dis 2007 Mar 195(5):739-47
Peripheral blood mononuclear cells from subjects never exposed to *
Leishmania* were stimulated with *Leishmania* guyanensis. We demonstrated
that L. guyanensis-stimulated CD8(+) T cells produced interferon (IFN)-
gamma and preferentially expressed the V beta 14 T cell receptor (TCR) gene
family. In addition, these cells expressed cutaneous lymphocyte antigen and
CCR4 surface molecules, suggesting that they could migrate to the skin.
Results obtained from the lesions of patients with localized cutaneous
leishmaniaisis (LCL) showed that V beta 14 TCR expression was increased in
most lesions (63.5%) and that expression of only a small number of V beta
gene families (V beta 1, V beta 6, V beta 9, V beta 14, and V beta 24) was
increased. The presence of V beta 14 T cells in tissue confirmed the
migration of these cells to the lesion site. Thus, we propose the following
sequence of events during infection with L. guyanensis. After initial
exposure to L. guyanensis, CD8(+) T cells preferentially expressing the V
beta 14 TCR and secreting IFN- gamma develop and circulate in the periphery.
During the infection, these cells migrate to the skin at the site of the
parasitic infection. The role of these V beta 14 CD8(+) T cells in
resistance to infection remains to be determined conclusively.


PMID: 17257310<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=17257310>
TITLE: Molecular dissection and expression of the LdK39 kinesin in the human
pathogen, *Leishmania*
donovani.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17257310>
AUTHORS: Noel J Gerald, Isabelle Coppens, Dennis M Dwyer
AFFILIATION: Cell Biology Section, Laboratory of Parasitic Diseases,
NIAID/NIH, Bethesda, MD, USA.
REFERENCE: Mol Microbiol 2007 Feb 63(4):962-79
In this study we show for the first time the intracellular distribution of a
K39 kinesin homologue in *Leishmania* donovani, a medically important
parasite of humans. Further, we demonstrated that this motor protein is
expressed in both the insect and mammalian developmental forms (i.e.
promastigote and amastigotes) of this organism. Moreover, in both of these
parasite developmental stages, immunofluorescence indicated that the LdK39
kinesin accumulated at anterior and posterior cell poles and that it
displayed a peripheral localization consistent with the cortical
cytoskeleton. Using a molecular approach, we identified, cloned and
characterized the first complete open reading frame for the gene (LdK39 )
encoding this large (> 358 kDa) motor protein in L. donovani. Based on these
observations, we subsequently used a homologous episomal expression system
to dissect and express the functional domains that constitute the native
molecule. Cell fractionation experiments demonstrated that LdK39 was soluble
and that it bound to detergent- extracted cytoskeletons of these parasites
in an ATP-dependent manner. The cumulative results of these experiments are
consistent with LdK39 functioning as an ATP-dependent kinesin which binds to
and travels along the cortical cytoskeleton of this important human
pathogen.


PMID: 16945323<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=16945323>
TITLE: Interaction of sitamaquine with membrane lipids of
*Leishmania*donovani
promastigotes.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16945323>
AUTHORS: Ana Maria Dueñas-Romero, Philippe M Loiseau, Michèle
Saint-Pierre-Chazalet
AFFILIATION: Groupe ChimiothÃ(c)rapie Antiparasitaire, UMR 8076 CNRS,
FacultÃ(c)
de Pharmacie, UniversitÃ(c) Paris-Sud XI, rue Jean-Baptiste ClÃ(c)ment,
F-92290-Châtenay-Malabry, France.
REFERENCE: Biochim Biophys Acta 2007 Feb 1768(2):246-52
Sitamaquine is an 8-aminoquinoline which is active by the oral route for the
treatment of life-threatening visceral leishmaniasis caused by
*Leishmania*donovani, with an IC(50) of
29.2 muM against the promastigote form in vitro. At high concentration (100
muM), sitamaquine affected parasite motility, morphology and growth in a way
that was only partially reversible. As a first approach to determine its
mechanism of action, we describe the interaction of sitamaquine with
parasite membrane components, representing the first barrier to be crossed
by the drug. Analysis of the physicochemical interactions of sitamaquine
with monolayers of phospholipids and sterols at the air-water interface
showed that these interactions only occurred in the presence of anionic
phospholipids. Thus, electrostatic interactions between positively charged
sitamaquine and the negative polar headgroups are a pre- requisite for
subsequent hydrophobic interactions between the sitamaquine aromatic ring
and the alkyl chains of phospholipids leading to drug insertion into the
monolayer.


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PMID: 17259689<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=17259689>
TITLE: Oral ulcer as an unusual feature of visceral leishmaniasis in an AIDS
patient.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17259689>
AUTHORS: Pramod Kumar, P K Sharma, R K Jain, R K Gautam, M Bhardwaj, H K Kar
AFFILIATION: Department of Dermatology, Dr. Ram Manohar Lohia Hospital, New
Delhi, India,. kumarpramod5 at rediffmail.com.
REFERENCE: Indian J Med Sci 2007 Feb 61(2):97-101
Leishmaniasis, a globally prevalent parasitic disease, occurs in three
forms, viz, visceral, cutaneous and mucocutaneous. It is transmitted by
female Phlebotomus sandflies. Human immunodeficiency virus (HIV) infection
is increasing worldwide and several reports indicate a rising trend of VL /
HIV co-infection, modifying the traditional anthroponotic pattern of VL
transmission. India is one of the countries having the largest burden of
leishmaniasis; nevertheless, there are very few HIV /
*leishmania*co-infection cases reported so far. We report a
35-year-old homemaker
infected with the human immunodeficiency virus; she presented with an oral
ulcer. The investigations carried out on her revealed that she was afflicted
by visceral leishmaniasis and the oral ulceration was a part of the same.
This is only the second such case from the Indian subcontinent and more
significantly from a non-endemic area.


PMID: 16945542<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=16945542>
TITLE: Synthesis of 2,4,6-trisubstituted pyrimidine and triazine
heterocycles as antileishmanial
agents.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16945542>
AUTHORS: Naresh Sunduru, Anu Agarwal, Sanjay Babu Katiyar, Nishi, Neena
Goyal, Suman Gupta, Prem M S Chauhan
AFFILIATION: Division of Medicinal Chemistry, Central Drug Research
Institute, Lucknow 226001, India.
REFERENCE: Bioorg Med Chem 2006 Dec 14(23):7706-15
A series of 2,4,6 trisubstituted pyrimidines and triazines have been
synthesized and screened for its in vitro antileishmanial activity profile
in promastigote model. Nine compounds have shown > 94% inhibition against
promastigotes at a concentration of 10 microg/mL.


PMID: 17176341<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=17176341>
TITLE: Comparative evaluation of freeze-dried and liquid antigens in the
direct agglutination test for serodiagnosis of visceral leishmaniasis
(ITMA-DAT/VL).<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17176341>
AUTHORS: Diane Jacquet, Marleen Boelaert, Jill Seaman, Suman Rijal, Shyam
Sundar, Joris Menten, Eddy Magnus
AFFILIATION: Applied Technology and Production Unit, Institute of Tropical
Medicine, Antwerp, Belgium. djacquet at itg.be
REFERENCE: Trop Med Int Health 2006 Dec 11(12):1777-84
OBJECTIVE: The direct agglutination test (DAT) for visceral leishmaniasis
(VL) with liquid (LQ) antigen is known to be only moderately reproducible
because of inter-observer and batch-to-batch variability as well as its
sensitivity to temperature and shaking during transport. We evaluated a DAT
with freeze-dried (FD) antigen and compared it with the LQ antigen version.
METHODS: Blood samples of clinical VL suspects and healthy endemic controls
were collected in Sudan, Nepal and India. Both test versions were performed
in duplicate in the respective countries and in the reference laboratory.
Interbatch variability and stability tests were conducted and agreement was
examined within and between centres on a dichotomic scale by Cohen's kappa
as well as on a continuous scale through Bland-Altman plots. RESULTS: The FD
antigen remains fully active even after storage at 45 degrees C for 24
months. Using a cut-off titre of 1:6400, the agreement between the FD and
the LQ formats was excellent. CONCLUSION: The major advantages of FD antigen
are its better stability at higher temperatures and its longer shelf life,
which make it much more suitable than the LQ version for use in the field.


PMID: 17045480<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=17045480>
TITLE: Modification at the C9 position of the marine natural product
isoaaptamine and the impact on HIV-1, mycobacterial, and tumor cell
activity.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17045480>
AUTHORS: Waseem Gul, Nicholas L Hammond, Muhammad Yousaf, John J Bowling,
Raymond F Schinazi, Susan S Wirtz, Garcia de Castro Andrews, Carmen Cuevas,
Mark T Hamann
AFFILIATION: Department of Pharmacognosy and the National Center for Natural
Products Research (NCNPR), University of Mississippi School of Pharmacy, MS
38677, USA.
REFERENCE: Bioorg Med Chem 2006 Dec 14(24):8495-505
As part of an investigation to generate optimized drug leads from marine
natural pharmacophores for the treatment of neoplastic and infectious
diseases, a series of novel isoaaptamine analogs were prepared by coupling
acyl halides to the C9 position of isoaaptamine (2) isolated from the Aaptos
sponge. This library of new semisynthetic products was evaluated for
biological activity against HIV-1, Mtb, AIDS-OI, tropical parasitic
diseases, and cancer. Compound 4 showed potent activity against HIV-1
(EC(50) 0.47microg/mL), compound 19 proved to possess remarkable activity
against Mycobacterium intracellulare with an IC(50) and MIC value of 0.15and
0.31microg/mL, while compounds 4 and 17 possessed anti-leishmanial activity
with IC(50) values of 0.1 and 0. 4microg/mL, respectively. Compounds 16 and
17 showed antimalarial activity with EC(50) values of 230 and 240ng/mL,
respectively, and compound 14 exhibited an EC(50) of 0.05microM against the
Leukemia cell line K-562.


PMID: 16328362<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=16328362>
TITLE: Visceral leishmaniasis in a patient with Down
syndrome.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16328362>
AUTHORS: Claudia Colomba, Laura Saporito, Salvatore Giordano, Laura
Infurnari, Patrizia Ajovalasit, Lucina Titone
AFFILIATION: Istituto di Patologia Infettiva e Virologia, Università di
Palermo, Piazza Porta Montalto, 8-90134 Palermo, Italy.
claudia.colomba at libero.it
REFERENCE: Eur J Pediatr 2006 Feb 165(2):140


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PMID: 17264434<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=17264434>
TITLE: Chronic diarrhea and malabsorption caused by *Leishmania*
donovani.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17264434>
AUTHORS: Chalamalasetty Sreenivasa Baba, Govind K Makharia, Purva Mathur,
Ruma Ray, Siddhartha Datta Gupta, J C Samantaray
AFFILIATION: Department of Gastroenterology and Human Nutrition, All India
Institute of Medical Sciences, New Delhi 110 029, India.
govindmakharia at gmail.com.
REFERENCE: Indian J Gastroenterol 2006 Nov-Dec 25(6):309-10
Chronic diarrhea and malabsorption are uncommon in immunocompetent patients
with visceral leishmaniasis. We report two immunocompetent patients with
visceral leishmaniasis where the predominant presentation was chronic
diarrhea. One of them had clinically overt malabsorption and duodenal mucosa
was loaded with *Leishmania* donovani bodies. The other patient had diffuse
colonic aphthous and discrete ulcerations and *Leishmania* donovani bodies
were seen in the crush smears of the colonic mucosa. With amphotericin B,
there was reversal of malabsorption and healing of colonic ulcers.


PMID: 17265631<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=17265631>
TITLE: A comparison of promastigote and amastigote antigens of
*Leishmania*infantum in the diagnosis of visceral Leishmaniosis by
ELISA and IFA tests
in Turkey.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17265631>
AUTHORS: N AltintaÅŸ, Y Ozbel
AFFILIATION: Ege University Medical Faculty, Department of Parasitology,
Izmir, Turkey.
REFERENCE: J Egypt Public Health Assoc 1997 72(1-2):189-97
This study was designed to evaluate the ELISA and IFA tests for diagnosis of
visceral leishmaniosis (VL) using soluble and crude antigens from
promastigote and amastigote forms of *Leishmania* infantum. A total of 70
sera were tested, including 30 patients who were suspected for Leishmaniosis
(10 healthy persons, 10 patients with Toxoplasmosis, 10 patients with
Giardiosis). In the 30 patients suspected to have Leishmaniosis, smears were
prepared from bone marrow aspirates and all material aspirated was cultured
in NNN medium. The results were compared with those of parasitological and
serological tests. While 2 patients were serologically positive and
parasitologically negative from the 30 patients, 8 patients were
serologically and parasitologically positive. The amastigote and
promastigote antigens were 100% specific. Using these antigens with ELISA
and IFA tests did not result and diagnosis different than VL.


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PMID: 16778314<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=16778314>
TITLE: Visceral leishmaniasis (kala-azar): challenges
ahead.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16778314>
AUTHORS: R K Singh, H P Pandey, S Sundar
AFFILIATION: Infectious Diseases Research Laboratory, Department of
Medicine, Institute of Medical Sciences, Banaras Hindu University,Varanasi,
India. rakeshbhu at yahoo.com
REFERENCE: Indian J Med Res 2006 Mar 123(3):331-44
Indian visceral leishmaniasis (VL) is a parasitic disease caused by a
haemoflagellete *Leishmania* donovani and transmitted by the bite of sand
fly Phlebotomus argentipes. It affects various age groups. In India about
1,00,000 cases of VL are estimated to occur annually; of these, the State of
Bihar accounts for over than 90 per cent of the cases. Diagnosis of VL
typically relies on microscopic examination of tissue smears but serology
and molecular methods are better alternatives currently. Notwithstanding the
growing incidence of resistance, pentavalent antimony complex has been the
mainstay for the treatment of VL during the last several decades. The second
line drugs such as amphotericin B, lipid formulations of amphotericin B,
paromomycin and recently developed miltefosine are the other alternatives.
In spite of significant development in various areas of
*Leishmania*research, there is a pressing need for the technological
advancement in the
understanding of immune response, drug resistance and the pathogenesis of
leishmaniasis that could be translated into field applicable and affordable
methods for diagnosis, treatment, and control of the disease.


PMID: 16259128<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=16259128>
TITLE: Screening of *Leishmania* APRT enzyme
inhibitors.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16259128>
AUTHORS: A R P Ambrozin, A C Leite, M Silva, P C Vieira, J B Fernandes, O H
Thiemann, M F das G F da Silva, G Oliva
AFFILIATION: Departamento de Química, Universidade Federal de São Carlos,
Brazil.
REFERENCE: Pharmazie 2005 Oct 60(10):781-4
Adenine phosphoribosyltransferase (APRT) enzyme from *Leishmania* tarentolae
has been proposed as a target for the rational search of new leishmanicidal
drugs. In this paper, we describe the evaluation of the inhibitory activity
on L. tarentolae APRT enzyme of 46 crude extracts of Meliaceae and Rutaceae
plants, besides three furoquinolone alkaloids. The results showed that 21
extracts were able to decrease the APRT enzymatic activity (IA% > or = 50).
The methanolic extracts from roots and leaves of Cedrela fissilis and from
fruits, branches and leaves of Cipadessa fruticosa have showed strong
activities. Therefore, these species could be a promising source of lead
compounds for the rational design of new leishmanicidal drugs. The
phytochemical investigation of an active fraction from Almeidea rubra
afforded the alkaloids isodutaduprine, isoskimmianine and isokokusagine,
which showed low to moderate activity on APRT.


PMID: 15587590<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=15587590>
TITLE: Inhibition of both Trypanosoma brucei bloodstream form and related
glycolytic enzymes by a new kolavic acid derivative isolated from Entada
abyssinica.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15587590>
AUTHORS: B Nyasse, I Ngantchou, E M Tchana, B SonkÃ(c), C Denier, C Fontaine
AFFILIATION: Laboratory of Bio-organic and Medicinal Chemistry, Department
of Organic Chemistry, Faculty of Science, University of Yaounde I, Cameroon.
bnyasse at uycdc.uninet.cm
REFERENCE: Pharmazie 2004 Nov 59(11):873-5
A new kolavic acid derivative known from spectroscopic analyses as
monomethyl ester-15-kolavic acid was isolated from the stem bark of Entada
abyssinica, a plant traditionally used in West and East Africa for the
management of sleeping sickness. The new derivative showed a strong and
selective inhibitory activity on the GAPDH enzyme of Trypanosoma brucei with
an IC50 value of 0.012 mM.


PMID: 15074591<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=15074591>
TITLE: Formulation and evaluation of oil-in-water emulsions of piperine in
visceral leishmaniasis.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15074591>
AUTHORS: P R Veerareddy, V Vobalaboina, A Nahid
AFFILIATION: University College of Pharmaceutical Sciences, Kakatiya
University, Warangal, Andhra Pradesh, India.
REFERENCE: Pharmazie 2004 Mar 59(3):194-7
Present studies are aimed to find out the utility of oil-in-water emulsions
also known as lipid nanospheres (LN) or fat emulsions for delivering
piperine for the treatment of visceral leishmaniasis. Lipid nanosphere
formulations of piperine were prepared using soybean oil, egg lecithin,
cholesterol, stearylamine and phosphatidylethanolamine
distearylmethoxypolyethyleneglycol (DSPE-PEG) by homogenization followed by
ultrasonication of oil and aqueous phases. Antileishmanial activity of all
the formulations was assessed in BALB/c mice infected with
*Leishmania*donovani AG83 for 60 days. A single dose (5 mg/kg) of
piperine, or lipid
nanospheres of piperine (LN-P), or lipid nanosphere of piperine with
stearylamine (LN-P-SA) or pegylated lipid nanospheres of piperine (LN-P-PEG)
was injected intravenously. Mice were sacrificed after 15 days of treatment
with piperine or formulations and Leishman Donovan Unit (LDU) is counted.
Toxicity of formulations and pure piperine was assessed in normal mice. The
size distribution of formulations ranged from 200 to 885 nm. Piperine
reduced the parasite burden in liver and spleen by 38% and 31% after 15 days
post infection respectively. LN-P reduced the parasite burden in liver and
spleen by 63 % and 52% after 15 days post infection, respectively. LN-P-PEG
reduced the parasite burden in liver and spleen by 78% and 75% after 15 days
post infection, respectively. LN-P-SA reduced the parasite burden in liver
and spleen by 90% and 85% after 15 days post infection, respectively. LN-P,
LN-P-PEG, LN-P-SA treated mice did not show any significant changes in the
serum levels of SGOT, ALP, creatinine and urea compared to normal mice.
Stable and sterile formulations of lipid nanospheres of piperine were
developed. A single dose of 5 mg/kg of lipid nanospheres of piperine could
significantly reduce the liver and splenic parasite burden.


PMID: 14651635<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=14651635>
TITLE: Heterologous expression of a mammalian protein tyrosine phosphatase
gene in *Leishmania*: effect on
differentiation.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=14651635>
AUTHORS: Mirna Nascimento, Nay Abourjeily, Anirban Ghosh, Wen Wei Zhang,
Greg Matlashewski
AFFILIATION: Department of Microbiology of Microbiology and Immunology, 3775
University Street, McGill University, Montreal, Quebec, Canada, H3A 2B4.
REFERENCE: Mol Microbiol 2003 Dec 50(5):1517-26
*Leishmania* is a protozoan pathogen which is transmitted to humans through
the bite of an infected sandfly. This infection results in a spectrum of
diseases throughout the developing world, collectively known as
leishmaniasis. During its life cycle, *Leishmania* differentiates from the
promastigote stage in the sandfly vector into the amastigote stage in the
mammalian host where it multiplies exclusively in macrophage phagolysosomes.
Although differentiation of *Leishmania* is essential for its survival and
pathogenesis in the mammalian host, this process is poorly understood. In
higher eukaryotic cells, protein tyrosine phosphorylation plays a central
role in cell proliferation, differentiation and overall function. We have
therefore investigated the role of protein tyrosine phosphorylation in *
Leishmania* differentiation by undertaking complementary approaches to
mediate protein tyrosine dephosphorylation in vivo. In the present study, L.
donovani were engineered to express a mammalian protein tyrosine
phosphatase, or were treated with inhibitors of protein tyrosine kinases,
and the resulting phenotype was examined. Both approaches resulted in a
partial differentiation from promastigotes to amastigotes including the
expression of the amastigote specific A2 protein, morphological change and
increased virulence. These data provide support for the involvement of
tyrosine phosphorylation in the differentiation of *Leishmania*.


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PMID: 11745335<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=11745335>
TITLE: Role of host phosphotyrosine phosphatase SHP-1 in the development of
murine leishmaniasis.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11745335>
AUTHORS: G Forget, K A Siminovitch, S Brochu, S Rivest, D Radzioch, M
Olivier
AFFILIATION: Centre de Recherche en Infectiologie CHUQ, UniversitÃ(c) Laval,
Ste-Foy, QuÃ(c)bec, Canada.
REFERENCE: Eur J Immunol 2001 Nov 31(11):3185-96
Activation of host phosphotyrosine phosphatase SHP-1 by *Leishmania* and its
subsequent impact on tyrosine phosphorylation-based signaling cascades were
shown to represent an important mechanism whereby this pathogen may alter
host cell functions. Herein, we report that *Leishmania*-induced macrophage
SHP-1 activity is necessary for its survival within phagocytes through the
attenuation of nitric oxide- dependent and -independent microbicidal
mechanisms. In vivo, *Leishmania* major infection, which footpad
inflammation is mostly undetectable in SHP-1-deficient viable motheaten
mice, was accompanied by increased inducible nitric oxide synthase and
activation of neutrophils. These enhanced cellular activities were
paralleled by a marked activation of signaling events usually negatively
regulated by SHP-1. Overall, this study firmly establishes that modulation
of the signaling terminator SHP -1 by *Leishmania* is essential for its
installment and propagation.


PMID: 10989833<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=10989833>
TITLE: New pyrazolo[3,4-b]pyrazines: synthesis and biological
activity.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10989833>
AUTHORS: H S el-Kashef, T I el-Emary, M Gasquet, P Timon-David, J Maldonado,
P Vanelle
AFFILIATION: Chemistry Department, Faculty of Science, Assiut University,
Egypt. elkashef at aun.eun.eg
REFERENCE: Pharmazie 2000 Aug 55(8):572-6
Some new pyrazolo[3,4-b]pyrazines and related heterocycles were synthesized
and evaluated for their antifungal and antiparasitic activities. The key
intermediate, 6-amino-3-methyl-1-phenyl-1H-pyrazolo[
3,4-b]pyrazine-5-carbonitrile (3) was obtained in a one-pot synthesis via
the reaction of 5-amino-3-methyl-4-nitroso-1-phenylpyrazole 2 with
malononitrile.


PMID: 10798254<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=10798254>
TITLE: Antifungal and antiprotozoal activities of saponins from Hedera
colchica.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10798254>
AUTHORS: V Mshvildadze, A Favel, F Delmas, R Elias, R Faure, G Decanosidze,
E Kemertelidze, G Balansard
AFFILIATION: Institute of Pharmacochemistry, Academy of Sciences, Tbilisi,
Georgia.
REFERENCE: Pharmazie 2000 Apr 55(4):325-6


PMID: 10556830<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=10556830>
TITLE: *Leishmania*-induced increases in activation of macrophage SHP-1
tyrosine phosphatase are associated with impaired IFN-gamma-triggered JAK2
activation.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10556830>
AUTHORS: J Blanchette, N Racette, R Faure, K A Siminovitch, M Olivier
AFFILIATION: Centre de Recherche en Infectiologie Laval University Medical
Research Center, UniversitÃ(c) Laval, Ste-Foy, Canada.
REFERENCE: Eur J Immunol 1999 Nov 29(11):3737-44
*Leishmania*-induced macrophage (Mphi) dysfunctions have been correlated
with altered signaling events. Recent findings from our laboratory suggest
that modulation of host protein tyrosine phosphatase (PTP) following *
Leishmania* infection could lead to these Mphi defects. To address this
issue, Mphi PTP activity and IFN-gamma-inducible signaling events were
evaluated in *Leishmania* donovani (Ld)-infected cells. We observed that Ld
promastigotes can rapidly trigger host PTP activity simultaneously with
dephosphorylation of Mphi protein tyrosyl residues and inhibition of protein
tyrosine kinase (PTK). Our results further revealed that Mphi SHP-1 PTP was
rapidly activated by the infection. This Ld-evoked signaling alteration was
reflected by absence of IFN- gamma-induced intracellular phosphorylation.
IFN-gamma-inducible JAK2 PTK phosphorylation was also markedly diminished in
Ld-infected cells. We also observed that co-immunoprecipitation of JAK2 with
SHP-1 was considerably higher in infected as compared to uninfected cells.
Altogether, these results suggest that SHP-1-mediated JAK2 dephosphorylation
triggered by *Leishmania* is partly responsible for abnormal Mphi IFN-gamma
signaling and represent an important mechanism supporting persistent
parasitic infection.


PMID: 10417174<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=10417174>
TITLE: Activation of phosphotyrosine phosphatase activity attenuates
mitogen-activated protein kinase signaling and inhibits c-FOS and nitric
oxide synthase expression in macrophages infected with
*Leishmania*donovani.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10417174>
AUTHORS: D Nandan, R Lo, N E Reiner
AFFILIATION: Department of Medicine (Division of Infectious Diseases),
Faculty of Medicine, University of British Columbia, Vancouver, British
Columbia, Canada V5Z 3J5.
REFERENCE: Infect Immun 1999 Aug 67(8):4055-63
Intracellular protozoan parasites of the genus *Leishmania* antagonize host
defense mechanisms by interfering with cell signaling in macrophages. In
this report, the impact of *Leishmania* donovani on mitogen-activated
protein (MAP) kinases and nitric oxide synthase (NOS) expression in the
macrophage cell line RAW 264 was investigated. Overnight infection of cells
with *leishmania* led to a significant decrease in
phorbol-12-myristate-13-acetate (PMA)-stimulated MAP kinase activity and
inhibited PMA-induced phosphorylation of the MAP kinase substrate and
transcription factor Elk-1. Simultaneously, *leishmania* infection markedly
attenuated the induction of c-FOS and inducible nitric oxide synthase (iNOS)
expression in response to PMA and gamma interferon (IFN-gamma),
respectively. These effects correlated with decreased phosphorylation of p44
and p42 MAP kinases on tyrosine residues. Consistent with the latter
finding, lysates prepared from *leishmania*-infected cells contained an
activity that dephosphorylated MAP kinase in vitro, suggesting the
possibility of a phosphatase acting in vivo. Attenuation of both MAP kinase
activity and c-FOS and iNOS expression was reversed by treatment of
macrophages with sodium orthovanadate prior to infection. It was also found
that the specific activity of the Src homology 2 domain containing tyrosine
phosphatase ( SHP-1) toward MAP kinase was markedly increased in *leishmania
*-infected cells. These findings indicate that infection with L. donovani
attenuates MAP kinase signaling and c-FOS and iNOS expression in macrophages
by activating cellular phosphotyrosine phosphatases. This may represent a
novel mechanism of macrophage deactivation during intracellular infection.


PMID: 8115445<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-06.xml&id=8115445>
TITLE: Substructures of CNS pharmaceuticals show additional antiprotozoan
action.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=8115445>
AUTHORS: A Gruska, R Franke, M Vogel, D Herrmann, B Hegenscheid, W Presber
AFFILIATION: Institute of Medical Microbiology, Berlin.
REFERENCE: Pharmazie 1993 Dec 48(12):950-1


REQUEST: [ sand fly NOT culicoides ]
(1 article matches this request. 1 article matching other requests removed)

REQUEST: [ sandfly NOT culicoides ]
(1 article matches this request. 1 article matching other requests removed)

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