[leish-l] Fwd: Articles found by RefScout 20/07/05 - 29/2005
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REQUEST: [ leishmaniasis ]
(16 articles match this request. 2 articles matching other requests removed)
PMID: 16005255
TITLE: Increased DNA damage and oxidative stress in patients with cutaneous
leishmaniasis.
AUTHORS: Abdurrahim Kocyigit, Huseyin Keles, Sahbettin Selek, Salih Guzel, Hakim
Celik, Ozcan Erel
AFFILIATION: Harran University, Medical Faculty, Department of Biochemistry,
63200 Sanliurfa, Turkey.
REFERENCE: Mutat Res 2005 Aug 585(1-2):71-8
Cutaneous leishmaniasis (CL) is a chronic infectious and granulomatous
disease caused by the Leishmania parasite that invades the skin.
Reactive oxygen and nitrogen species (ROS and RNS) produced during an
inflammatory response are an important part of host-defense strategies
of organisms to kill the parasite. However, it is not well known whether
these intermediates cause DNA damage in CL patients. We investigated
the effect of Leishmania infection on basal levels of DNA strand breaks
and on the oxidative/anti-oxidative status of patients with CL, and
compared the data with those of healthy subjects. Twenty-five CL
patients and 19 age- and sex-matched control subjects were enrolled in
the study. We used the single-cell gel electrophoresis (also called
comet assay) to measure DNA strand breaks in peripheral blood
mononuclear leukocytes. Plasma protein carbonyl (PC), malondialdehyde (
MDA) and total peroxide (TP) concentrations were measured to determine
oxidative status and total anti-oxidative response (TAR) in plasma was
measured to determine anti-oxidative status. The mean values of DNA
damage and MDA and TP concentrations were significantly higher in CL
patients than in the control group (p<0.001, p<0.01 and p<0.001
, respectively). PC levels were also higher in patients, but this was
not statistically significant (p>0.05). There was a significantly
positive correlation between plasma MDA and DNA damage (r=0.524, p<0.
01), and a negative correlation between TAR and TP levels (r=-0.790, p&
lt;0.001) in the patient group. These findings support the notion that
ROS and RNS produced by the organism as a defense strategy may amplify
the leishmanicidal activity in patients with CL. However, these
intermediates not only cause the killing of the parasite but also induce
oxidative damage in non-infected cells. Therefore, these patients must
be treated urgently to counteract the oxidative DNA damage.
PMID: 15967724
TITLE: Insights into CD4(+) memory T cells following Leishmania infection.
AUTHORS: Kenneth J Gollob, Lis R V Antonelli, Walderez O Dutra
AFFILIATION: Department of Biochemistry and Immunology, Federal University of
Minas Gerais, Institute for Biological Sciences, Belo Horizonte 30161-970,
Brazil.
REFERENCE: Trends Parasitol 2005 Aug 21(8):347-50
Recent publications by Zaph et al. have highlighted the distinct
requirements for generating and maintaining different subpopulations of
CD4(+) memory T cells after infection with Leishmania major in mice.
These studies have advanced the understanding of the nature of long-
lasting immunity to Leishmania and, when considered within the context
of previous work on both murine and human leishmaniasis, will aid the
design of effective vaccines.
PMID: 16013987
TITLE: Miltefosine to treat leishmaniasis.
AUTHORS: Jonathan Berman
AFFILIATION: Office of Clinical and Regulatory Affairs National Center For
Complementary and Alternative Medicine National Institutes of Health, 6707
Democracy Blvd, Suite 401 Bethesda MD 20892 USA. Bermanjo at mail.nih.gov.
REFERENCE: Expert Opin Pharmacother 2005 Jul 6(8):1381-8
Leishmaniasis exists in both visceral and cutaneous forms, and
miltefosine is the first oral agent with demonstrable efficacy against
both types of this disease. At a dose of approximately 2.5 mg/kg/day for
28 days, miltefosine is > 90% curative for visceral disease in India
and cutaneous disease in Colombia. Miltefosine is a lecithin analogue
and its mechanism may be to inhibit phosphatidylcholine biosynthesis in
the causative parasites. The clinical half-life of miltefosine is
approximately 7 days. Whether or not miltefosine can be used for
widespread out-patient treatment of individuals and whole populations
depends on whether its efficacy and tolerability can be maintained in
further treatment trials.
PMID: 16014838
TITLE: Successful treatment of refractory cutaneous leishmaniasis with gm-csf
and antimonials.
AUTHORS: Roque P Almeida, Jussamara Brito, Paulo L Machado, Amélia R DE Jesus,
Albert Schriefer, Luiz Henrique Guimarães, Edgar M Carvalho
AFFILIATION: Serviço de Imunologia, Hospital Universitário Professor Edgard
Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Instituto de
Investigação em Imunologia (iii)/CNPq, São Paulo, Brazil.
REFERENCE: Am J Trop Med Hyg 2005 Jul 73(1):79-81
Therapeutic failure in the treatment of cutaneous leishmaniasis (CL)
occurs in 5% of patients infected by Leishmania braziliensis. This study
evaluates the use of topically applied granulocyte macrophage colony-
stimulating factor (GM-CSF) combined with the standard dose of antimony
to treat refractory cases of CL. Five patients who had received three
courses or more of antimony were enrolled in an open-label clinical
trial. One to 2 mL of the GM-CSF solution (10 mug/mL in 0.9% saline) was
reapplied topically, and dressings were changed three times per week
for 3 weeks, associated with standard parenteral antimony (20 mg kg(-1)
day(-1) for 20 days). All the patients healed their CL ulcers; 3 healed
within 50 days (21, 27, and 44 days) and 2 in 118 and 120 days after
beginning therapy. There were no side effects. This study shows that
combined topically applied GM-CSF and antimony can be effective and well
tolerated in the treatment of relapsed CL.
PMID: 16007964
TITLE: Bionomics of Phlebotomus papatasi (Diptera: Psychodidae) in an endemic
focus of zoonotic cutaneous leishmaniasis in central Iran.
AUTHORS: Mohammad R Yaghoobi-Ershadi, Amir A Akhavan, Ali R Zahraei-Ramazani,
Ali R Jalali-Zand, Norair Piazak
AFFILIATION: Department of Medical Entomology and Vector Control, School of
Public Health and Institute of Public Health Research, Tehran University of
Medical Sciences, P.O. Box 6446-14155, Tehran, IR iran
REFERENCE: J Vector Ecol 2005 Jun 30(1):115-8
Following an epidemiological survey of zoonotic cutaneous leishmaniasis
(ZCL) in several villages of Badrood, a rural district north of the
city of Natanz, central Iran, Phlebotomus (Phlebotomus) papatasi Scopoli
were found to be naturally infected with Leishmania (Leishmania) major
zymodeme MON-26. Sand flies were collected and dissected biweekly from
rodent burrows from May to October 2001. Leptomonad infection rates
varied between 6.7% and 22.0%, being greatest in September, coinciding
with peak activity of P. papatasi, two-three months before the highest
incidence of ZCL human cases in November-December. The leptomonad
infection rate was 1.1% of the 94 P. papatasi captured indoors. In ELISA
testing of 520 P. papatasi blood meals during Sept. 2001 and Aug. 2002
, the proportion giving positive reactions for human, sheep, cow, goat,
rodent, and bird were 31.2%, 69.6%, 63%, 38.8%, 24.7%, and 21.8%,
respectively. This report thus incriminates P. papatasi as the vector of
zoonotic cutaneous leishmaniasis in this part of Iran.
PMID: 15845279
TITLE: Epidemiological aspects of canine visceral leishmaniosis in the Islamic
Republic of Iran.
AUTHORS: Mehdi Mohebali, Homa Hajjaran, Yazdan Hamzavi, Iraj Mobedi, Shahnam
Arshi, Zabih Zarei, Behnaz Akhoundi, Koroush Manouchehri Naeini, Reza Avizeh,
Mehdi Fakhar
AFFILIATION: School of Public Health Research, Tehran University of Medical
Sciences, Department of Medical Parasitology, P.O. Box 14155-6446, Tehran,
Iran. mmohebali at hotmail.com
REFERENCE: Vet Parasitol 2005 May 129(3-4):243-51
An epidemiological study to examine the sero-prevalence of zoonotic
visceral leishmaniosis (ZVL) among domestic and wild canines in endemic
foci of Iran was carried out during 1999-2003 to assess the distribution
of the disease and the possible association between infection in dogs,
wild canines and people. Anti-leishmanial antibodies were detected by
the direct agglutination test (DAT). Parasitological study was performed
for all captured wild canines and were detected in some of the
seropositive dogs with specific clinical signs (n=107). Serum samples (n
=1568) were collected from domestic dogs in villages that are known
endemic foci of human visceral leishmaniosis (HVL). Wild canine sera
were collected from jackals (Canis aureus, n=10), foxes (Vulpes vulpes,
n=10) and wolves (Canis lupus, n=10). Of the 1568 serum sampled
collected from domestic dogs, 222 (14.2%) were positive by DAT (1:320
and above). No statistically significant difference was found between
male (15.2%) and female (11.8%) sero-prevalence (P=0.083). Dogs of 8
years and above showed the highest sero-prevalence (40.6%). Only 23.9%
of the seropositive domestic dogs had clinical signs. Parasitology and
serology tests that were performed in 30 wild canines showed 10% these
animals were infected by Leishmania infantum. Ten out of 11 Leishmania
spp. isolated from the dogs and wild canines were identified as L.
infantum and one other as L. tropica by molecular and biochemical
techniques. For the first time in Iran, L. infantum and L. tropica were
isolated from viscera of both a wolf and a domestic dog.
PMID: 15885089
TITLE: Quantitative assessment of the glyoxalase pathway in Leishmania infantum
as a therapeutic target by modelling and computer simulation.
AUTHORS: Marta Sousa Silva, António E N Ferreira, Ana Maria Tomás, Carlos
Cordeiro, Ana Ponces Freire
AFFILIATION: Centro de QuÃmica e BioquÃmica, Departmento de QuÃmica e
BioquÃmica, Faculdade de Ciências da Universidade de Lisboa, Portugal.
REFERENCE: FEBS J 2005 May 272(10):2388-98
The glyoxalase pathway of Leishmania infantum was kinetically
characterized as a trypanothione-dependent system. Using time course
analysis based on parameter fitting with a genetic algorithm, kinetic
parameters were estimated for both enzymes, with trypanothione derived
substrates. A K(m) of 0.253 mm and a V of 0.21 micromol.min(-1).mg(-1)
for glyoxalase I, and a K(m) of 0.098 mm and a V of 0.18 micromol.min(-1
).mg(-1) for glyoxalase II, were obtained. Modelling and computer
simulation were used for evaluating the relevance of the glyoxalase
pathway as a potential therapeutic target by revealing the importance of
critical parameters of this pathway in Leishmania infantum. A
sensitivity analysis of the pathway was performed using experimentally
validated kinetic models and experimentally determined metabolite
concentrations and kinetic parameters. The measurement of metabolites in
L. infantum involved the identification and quantification of
methylglyoxal and intracellular thiols. Methylglyoxal formation in L.
infantum is nonenzymatic. The sensitivity analysis revealed that the
most critical parameters for controlling the intracellular concentration
of methylglyoxal are its formation rate and the concentration of
trypanothione. Glyoxalase I and II activities play only a minor role in
maintaining a low intracellular methylglyoxal concentration. The
importance of the glyoxalase pathway as a therapeutic target is very
small, compared to the much greater effects caused by decreasing
trypanothione concentration or increasing methylglyoxal concentration.
PMID: 15976883
TITLE: Availability of miltefosine for the treatment of kala-azar in India.
AUTHORS: Shyam Sundar, Henry W Murray
AFFILIATION: Institute of Medical Sciences, Banaras Hindu University, 6 SK Gupta
Nagar, Lanka, Varanasi 221-005, India. shyam_vns at sify.com
REFERENCE: Bull World Health Organ 2005 May 83(5):394-5
PMID: 15845273
TITLE: Seroepidemiology of leptospirosis, toxoplasmosis, and leishmaniosis among
dogs in Ankara, Turkey.
AUTHORS: Ozkan Aslantaş, Vildan Ozdemir, Selçuk Kiliç, Cahit Babür
AFFILIATION: Mustafa Kemal University, Faculty of Veterinary Medicine,
Department of Microbiology, 31040 Antakya-Hatay, Turkey. aslantas at mku.edu.tr
REFERENCE: Vet Parasitol 2005 May 129(3-4):187-91
Seroprevalence of five different Leptospira interrogans serovars,
Toxoplasma gondii and Leishmania infantum in stray dogs in Ankara was
investigated. A total of 116 dog sera collected from apparently healthy
stray dogs were tested for L. interrogans serovars by microscopic
agglutination test (MAT), for T. gondii antibodies by Sabin-Feldman dye
test (SFDT), and for L. infantum antibodies by indirect fluorescence
antibody test (IFAT). Of the 116 dogs, 51 (43.96%) were seropositive for
leptospirosis, 72 (62.06%) for T. gondii and 3 (2.58%) for L. infantum
. No statistically significant difference was observed between male and
female dogs in the seroprevalences of toxoplasmosis and leptospirosis (P
>0.05), but statistically significant difference was observed among
different age groups in the seroprevalences of toxoplasmosis and
leptospirosis (P<0.05). Although the seroprevalence of L. infantum
was low, asymptomatic animals should be considered as a reservoir for
the spread of the disease.
PMID: 15716074
TITLE: CD40 signaling induces reciprocal outcomes in Leishmania-infected
macrophages; roles of host genotype and cytokine milieu.
AUTHORS: Marise P Nunes, Lea Cysne-Finkelstein, Bruna C Monteiro, Daniel M de
Souza, Nitza A Gomes, George A DosReis
AFFILIATION: Instituto Oswaldo Cruz, FIOCRUZ, Avenida Brasil, 4365, Rio de
Janeiro, RJ, 21045-900, Brazil.
REFERENCE: Microbes Infect 2005 Jan 7(1):78-85
We investigated the influence of CD40-CD40 ligand-mediated signaling on
induction of microbicidal activity against Leishmania major in
macrophages from resistant (B6) and susceptible (BALB) mouse strains.
CD40 engagement induced leishmanicidal activity in resistant macrophages
, but increased parasite replication in susceptible macrophages. CD40
engagement induced comparable TNF-alpha production in macrophages from
both strains. However, increased IL-10 production was restricted to
susceptible macrophages. Increased parasite replication in susceptible
macrophages was prevented by a neutralizing anti-IL-10 antibody. In the
presence of IFN-gamma, CD40 engagement induced Leishmania killing by
macrophages from both strains. Therefore, the outcome of CD40 signaling
on effector responses against L. major depends on host genotype and the
cytokine milieu, and a source of IFN-gamma is required for a protective
response.
PMID: 16020131
TITLE: HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS ASSOCIATED WITH VISCERAL
LEISHMANIASIS: A Case Report.
AUTHORS: Emel Ozyürek, Figen Ozcay, Basak Yilmaz, Namik Ozbek
AFFILIATION: Department of Pediatrics, Baskent University, Faculty of Medicine,
Adana Teaching and Medical Research Center, Adana, Turkey.
REFERENCE: Pediatr Hematol Oncol 2005 Jul-Aug 22(5):409-14
Leishmania-associated hemophagocytic lymphohistiocytosis is a rare
clinicopathological entity. This condition is often difficult to
diagnose, so treatment is often delayed. This report describes the case
of a 5-year-old boy who was admitted with fever of 1 month's duration,
hepatosplenomegaly, and pancytopenia. Serum testing showed elevated
transaminase levels, hypertriglyceridemia, hyperferritinemia, and normal
fibrinogen level. Hemophagocytic lymphohistiocytosis was diagnosed on
bone marrow examination. The patient was tested for various infectious
agents. He was negative for all except Leishmania, which was detected by
indirect fluorescent antibody testing. Treatment with amphotericin B
resulted in a dramatic resolution of all signs and symptoms within 1
week.
PMID: 15996442
TITLE: Epidemiology of travel-related hospitalization.
AUTHORS: Shmuel Stienlauf, Gad Segal, Yechezkel Sidi, Eli Schwartz
AFFILIATION: Department of Internal Medicine C, Sheba Medical Center, Tel Aviv
University, Israel.
REFERENCE: J Travel Med 2005 May-Jun 12(3):136-41
BACKGROUND: Limited information exists on causes of hospitalization in
patients returning from the tropics, and most is focused on febrile
diseases. We evaluated all causes of post-travel hospitalization in a
tertiary care hospital in Israel. METHOD: Demographics, diagnoses, and
destinations of patients admitted between January 1999 and December 2003
with a history of recent travel were recorded. Demographics and
destination of healthy travelers presenting to our pretravel clinic at
the same period were recorded. RESULTS: Of 211 patients admitted, 71%
were males, 8% were immigrants/foreign workers, and febrile diseases
accounted for 77% of admissions. The most common diagnoses were malaria
in 54 (26%), unidentified febrile disease in 34 (16%), and dengue fever
in 27 (13%). New World cutaneous leishmaniasis was the most common cause
of admission among nonfebrile patients (18 [9%]). Diarrheal diseases
accounted for only 11% of admissions. Regarding destination, 101 (48%)
patients had been to Asia, 71 (34%) to Africa, and 43 (20%) to the
Americas. Of our healthy traveler population, 59% traveled to Asia, 20%
to Africa, and 20% to the Americas. Travel to Africa carried the highest
risk of being hospitalized (OR 1.85, 95% CI 1.16-2.97; p = .01). Most (
59%) patients returning from Africa had malaria. The principal health
problem originating in Asia was dengue fever (27%), and from Latin
America, cutaneous leishmaniasis (48%). Males comprised 71% of the
patients, and 59% of the healthy traveler population (p < .0001).
Males were more likely to acquire malaria (OR 2.15, 95% CI 1.13-4.09; p
= .02) and leishmaniasis (OR 3.41, 95% CI 0.97-11.89; p = .05).
CONCLUSIONS: Febrile diseases were the most common cause for
hospitalization, with malaria, unidentified febrile diseases, and dengue
fever being the most common. Diseases were destination related; travel
to Africa was associated with a higher rate of hospitalization. Malaria
and cutaneous leishmaniasis had a substantially male predominance,
probably due to risk-taking behavior.
PMID: 15991984
TITLE: Imiquimod 5% cream (Aldara).
AUTHORS: H B Slade, M L Owens, M A Tomai, R L Miller
AFFILIATION: 3M Pharmaceuticals, Medical Affairs Building 270-3A-01, St Paul, MN
55144-1000, USA. hbslade at mmm.com
REFERENCE: Expert Opin Investig Drugs 1998 Mar 7(3):437-49
Imiquimod is a novel synthetic molecule with potent immune-modifying
activities. Formulated in a 5% vanishing cream as Aldara, this self-
applied therapy has shown good efficacy and safety in the treatment of
external genital and perianal warts caused by human papillomavirus (HPV
) infection (Condyloma acuminata). The molecule does not demonstrate
direct antiviral activity, but through induction of cytokines results in
immune-based resolution of wart tissue and reduction of viral burden.
Phase III trials of imiquimod have demonstrated that patients who
experience complete clearance of either new or recalcitrant warts tend
to remain clear, possibly related to Th1 immune recognition and memory.
Self-application, good tolerability and a unique mechanism of action
combine to make imiquimod a reasonable first-line therapy for genital
warts. The effects of imiquimod on immune function suggest several
potential uses. Preclinical studies of infection with herpes simplex
virus (HSV), cutaneous leishmaniasis, Rift Valley Fever virus and
vesiculostomatitis virus have shown reduced viral persistence, reduced
recurrence (HSV) and diminished pathology (Leishmania donovani). In a
murine tumour model using the FCB bladder cancer cell line, imiquimod
behaves as a potent adjuvant leading to immune-based tumour cell
eradication and immunity against subsequent FCB cell challenge. The
ability of imiquimod to induce significant production of interferon
alpha (IFN-alpha) by monocytes/macrophages suggests that diseases
responsive to recombinant interferon therapy, such as basal cell
carcinoma, may be reasonable clinical targets. The induction of tumour
necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and
interleukin-12 (IL-12) leads to inhibition of IL-5, with animal models
demonstrating immune deviation away from Th2 immune responses. The
observation that several patients with hepatitis C infection and
eosinophilia showed normalisation of elevated eosinophil counts in
association with oral imiquimod therapy encourages further exploration
of the immune modifying properties of this novel molecule. This review
is focused on the use of imiquimod for the treatment of external genital
and perianal warts.
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PMID: 15817202
TITLE: Osteolytic osteomyelitis associated with visceral leishmaniasis in a
dog.
AUTHORS: Alda Izabel de Souza, Raquel Soares Juliano, Tatiana Scanoni Gomes,
Soraia de Araujo Diniz, Alan Maia Borges, Wagner Luiz Tafuri, Renato Lima
Santos
AFFILIATION: Curso de Medicina Veterinária, Centro de Ciências Biológicas,
Agrárias e da Saúde (CCBAS), Universidade para o Desenvolvimento do Estado e
da Região do Pantanal (UNIDERP), Rua Alexandre Herculano 1400, 79037-280 Campo
Grande, MS, Brazil. alda at nin.ufms.br
REFERENCE: Vet Parasitol 2005 Apr 129(1-2):51-4
A dog was examined with a history of weight loss and lameness of the
left hind limb. A painful response to examination of the left hip joint
, and lymphadenopathy were noted. Amastigote forms of Leishmania sp.
were observed by cytology in samples from the popliteus lymph node, and
anti-Leishmania sp. antibodies at a titer of 1:640 were detected in
serum by indirect immunofluorescence. Radiological changes included
osteolysis and a periosteal proliferative reaction in the left femoral
greater trochanter. These changes were histologically characterized as
an osteolytic granulomatous osteomyelitis associated with amastigotes
within macrophages. Non-decalcified fragments of the periosteum were
processed for immunohistochemistry, observed with prominent
immunolabelling of amastigotes of Leishmania sp. within macrophages. The
diagnosis was further confirmed by positive PCR for Leishmania sp.,
belonging to the Leishmania donovani complex.
REQUEST: [ leishmania ]
(24 articles match this request. 13 articles matching other requests removed)
PMID: 15967722
TITLE: Fellowship of the rings: the replication of kinetoplast DNA.
AUTHORS: Beiyu Liu, Yanan Liu, Shawn A Motyka, Eddy E C Agbo, Paul T Englund
AFFILIATION: Department of Biological Chemistry, Johns Hopkins Medical School,
725 North Wolfe Street, Baltimore, MD 21205, USA.
REFERENCE: Trends Parasitol 2005 Aug 21(8):363-9
Kinetoplastid protozoa such as trypanosomes and Leishmania are important
because they cause human disease. These parasites are named after one
of their most unusual features, a mitochondrial DNA known as kinetoplast
DNA (kDNA). Unlike all other DNA in nature, kDNA comprises a giant
network of interlocked DNA rings with a topology resembling that of
medieval chain mail. The replication of the kDNA network is more complex
than previously thought, and the discovery of new proteins involved in
this process is currently the best approach for illuminating the
replication mechanism.
PMID: 16020726
TITLE: The Genome of the African Trypanosome Trypanosoma brucei.
AUTHORS: Matthew Berriman, Elodie Ghedin, Christiane Hertz-Fowler, Gaëlle
Blandin, Hubert Renauld, Daniella C Bartholomeu, Nicola J Lennard, Elisabet
Caler, Nancy E Hamlin, Brian Haas, Ulrike Böhme, Linda Hannick, Martin A
Aslett, Joshua Shallom, Lucio Marcello, Lihua Hou, Bill Wickstead, U Cecilia M
Alsmark, Claire Arrowsmith, Rebecca J Atkin, Andrew J Barron, Frederic
Bringaud, Karen Brooks, Mark Carrington, Inna Cherevach, Tracey-Jane
Chillingworth, Carol Churcher, Louise N Clark, Craig H Corton, Ann Cronin, Rob
M Davies, Jonathon Doggett, Appolinaire Djikeng, Tamara Feldblyum, Mark C
Field, Audrey Fraser, Ian Goodhead, Zahra Hance, David Harper, Barbara R
Harris, Heidi Hauser, Jessica Hostetler, Al Ivens, Kay Jagels, David Johnson,
Justin Johnson, Kristine Jones, Arnaud X Kerhornou, Hean Koo, Natasha Larke,
Scott Landfear, Christopher Larkin, Vanessa Leech, Alexandra Line, Angela Lord,
Annette Macleod, Paul J Mooney, Sharon Moule, David M A Martin, Gareth W
Morgan, Karen Mungall, Halina Norbertczak, Doug Ormond, Grace Pai, Chris S
Peacock, Jeremy Peterson, Michael A Quail, Ester Rabbinowitsch, Marie-Adele
Rajandream, Chris Reitter, Steven L Salzberg, Mandy Sanders, Seth Schobel,
Sarah Sharp, Mark Simmonds, Anjana J Simpson, Luke Tallon, C Michael R Turner,
Andrew Tait, Adrian R Tivey, Susan Van Aken, Danielle Walker, David Wanless,
Shiliang Wang, Brian White, Owen White, Sally Whitehead, John Woodward,
Jennifer Wortman, Mark D Adams, T Martin Embley, Keith Gull, Elisabetta Ullu, J
David Barry, Alan H Fairlamb, Fred Opperdoes, Barclay G Barrell, John E
Donelson, Neil Hall, Claire M Fraser, Sara E Melville, Najib M El-Sayed
AFFILIATION: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus,
Hinxton CB10 1SA, UK.
REFERENCE: Science 2005 Jul 309(5733):416-22
African trypanosomes cause human sleeping sickness and livestock
trypanosomiasis in sub-Saharan Africa. We present the sequence and
analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The
26-megabase genome contains 9068 predicted genes, including
approximately 900 pseudogenes and approximately 1700 T. brucei-specific
genes. Large subtelomeric arrays contain an archive of 806 variant
surface glycoprotein (VSG) genes used by the parasite to evade the
mammalian immune system. Most VSG genes are pseudogenes, which may be
used to generate expressed mosaic genes by ectopic recombination.
Comparisons of the cytoskeleton and endocytic trafficking systems with
those of humans and other eukaryotic organisms reveal major differences
. A comparison of metabolic pathways encoded by the genomes of T. brucei
, T. cruzi, and Leishmania major reveals the least overall metabolic
capability in T. brucei and the greatest in L. major. Horizontal
transfer of genes of bacterial origin has contributed to some of the
metabolic differences in these parasites, and a number of novel
potential drug targets have been identified.
PMID: 16020728
TITLE: The Genome of the Kinetoplastid Parasite, Leishmania major.
AUTHORS: Alasdair C Ivens, Christopher S Peacock, Elizabeth A Worthey, Lee
Murphy, Gautam Aggarwal, Matthew Berriman, Ellen Sisk, Marie-Adele Rajandream,
Ellen Adlem, Rita Aert, Atashi Anupama, Zina Apostolou, Philip Attipoe,
Nathalie Bason, Christopher Bauser, Alfred Beck, Stephen M Beverley, Gabriella
Bianchettin, Katja Borzym, Gordana Bothe, Carlo V Bruschi, Matt Collins, Eithon
Cadag, Laura Ciarloni, Christine Clayton, Richard M R Coulson, Ann Cronin,
Angela K Cruz, Robert M Davies, Javier De Gaudenzi, Deborah E Dobson, Andreas
Duesterhoeft, Gholam Fazelina, Nigel Fosker, Alberto Carlos Frasch, Audrey
Fraser, Monika Fuchs, Claudia Gabel, Arlette Goble, André Goffeau, David
Harris, Christiane Hertz-Fowler, Helmut Hilbert, David Horn, Yiting Huang, Sven
Klages, Andrew Knights, Michael Kube, Natasha Larke, Lyudmila Litvin, Angela
Lord, Tin Louie, Marco Marra, David Masuy, Keith Matthews, Shulamit Michaeli,
Jeremy C Mottram, Silke Müller-Auer, Heather Munden, Siri Nelson, Halina
Norbertczak, Karen Oliver, Susan O'neil, Martin Pentony, Thomas M Pohl, Claire
Price, Bénédicte Purnelle, Michael A Quail, Ester Rabbinowitsch, Richard
Reinhardt, Michael Rieger, Joel Rinta, Johan Robben, Laura Robertson, Jeronimo
C Ruiz, Simon Rutter, David Saunders, Melanie Schäfer, Jacquie Schein, David C
Schwartz, Kathy Seeger, Amber Seyler, Sarah Sharp, Heesun Shin, Dhileep Sivam,
Rob Squares, Steve Squares, Valentina Tosato, Christy Vogt, Guido Volckaert,
Rolf Wambutt, Tim Warren, Holger Wedler, John Woodward, Shiguo Zhou, Wolfgang
Zimmermann, Deborah F Smith, Jenefer M Blackwell, Kenneth D Stuart, Bart
Barrell, Peter J Myler
AFFILIATION: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus,
Hinxton, Cambridgeshire CB10 1SA, UK.
REFERENCE: Science 2005 Jul 309(5733):436-42
Leishmania species cause a spectrum of human diseases in tropical and
subtropical regions of the world. We have sequenced the 36 chromosomes
of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain
) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding
genes, of which 36% can be ascribed a putative function. These include
genes involved in host-pathogen interactions, such as proteolytic
enzymes, and extensive machinery for synthesis of complex surface
glycoconjugates. The organization of protein-coding genes into long,
strand-specific, polycistronic clusters and lack of general
transcription factors in the L. major, Trypanosoma brucei, and
Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms
regulating RNA polymerase II-directed transcription are distinct from
those operating in other eukaryotes, although the trypanosomatids appear
capable of chromatin remodeling. Abundant RNA-binding proteins are
encoded in the Tritryp genomes, consistent with active
posttranscriptional regulation of gene expression.
PMID: 16008555
TITLE: 6-Phosphofructo-2-kinase and fructose-2,6-bisphosphatase in
Trypanosomatidae.
AUTHORS: Nathalie Chevalier, Luc Bertrand, Mark H Rider, Fred R Opperdoes,
Daniel J Rigden, Paul A M Michels
AFFILIATION: Research Unit for Tropical Diseases, Christian de Duve Institute of
Cellular Pathology and Laboratory of Biochemistry, Université catholique de
Louvain, Brussels, Belgium.
REFERENCE: FEBS J 2005 Jul 272(14):3542-60
Fructose 2,6-bisphosphate is a potent allosteric activator of
trypanosomatid pyruvate kinase and thus represents an important
regulator of energy metabolism in these protozoan parasites. A 6-
phosphofructo-2-kinase, responsible for the synthesis of this regulator
, was highly purified from the bloodstream form of Trypanosoma brucei
and kinetically characterized. By searching trypanosomatid genome
databases, four genes encoding proteins homologous to the mammalian
bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
(PFK-2/FBPase-2) were found for both T. brucei and the related parasite
Leishmania major and four pairs in Trypanosoma cruzi. These genes were
predicted to each encode a protein in which, at most, only a single
domain would be active. Two of the T. brucei proteins showed most
conservation in the PFK-2 domain, although one of them was predicted to
be inactive due to substitution of residues responsible for ligating the
catalytically essential divalent metal cation; the two other proteins
were most conserved in the FBPase-2 domain. The two PFK-2-like proteins
were expressed in Escherichia coli. Indeed, the first displayed PFK-2
activity with similar kinetic properties to that of the enzyme purified
from T. brucei, whereas no activity was found for the second.
Interestingly, several of the predicted trypanosomatid PFK-2/FBPase-2
proteins have long N-terminal extensions. The N-terminal domains of the
two polypeptides with most similarity to mammalian PFK-2s contain a
series of tandem repeat ankyrin motifs. In other proteins such motifs
are known to mediate protein-protein interactions. Phylogenetic analysis
suggests that the four different PFK-2/FBPase-2 isoenzymes found in
Trypanosoma and Leishmania evolved from a single ancestral bifunctional
enzyme within the trypanosomatid lineage. A possible explanation for the
evolution of multiple monofunctional enzymes and for the presence of
the ankyrin-motif repeats in the PFK-2 isoenzymes is presented.
PMID: 16020724
TITLE: Comparative genomics of trypanosomatid parasitic protozoa.
AUTHORS: Najib M El-Sayed, Peter J Myler, Gaëlle Blandin, Matthew Berriman,
Jonathan Crabtree, Gautam Aggarwal, Elisabet Caler, Hubert Renauld, Elizabeth A
Worthey, Christiane Hertz-Fowler, Elodie Ghedin, Christopher Peacock, Daniella
C Bartholomeu, Brian J Haas, Anh-Nhi Tran, Jennifer R Wortman, U Cecilia M
Alsmark, Samuel Angiuoli, Atashi Anupama, Jonathan Badger, Frederic Bringaud,
Eithon Cadag, Jane M Carlton, Gustavo C Cerqueira, Todd Creasy, Arthur L
Delcher, Appolinaire Djikeng, T Martin Embley, Christopher Hauser, Alasdair C
Ivens, Sarah K Kummerfeld, Jose B Pereira-Leal, Daniel Nilsson, Jeremy
Peterson, Steven L Salzberg, Joshua Shallom, Joana C Silva, Jaideep Sundaram,
Scott Westenberger, Owen White, Sara E Melville, John E Donelson, Björn
Andersson, Kenneth D Stuart, Neil Hall
AFFILIATION: Institute for Genomic Research, 9712 Medical Center Drive,
Rockville, MD 20850, USA. nelsayed at tigr.org
REFERENCE: Science 2005 Jul 309(5733):404-9
A comparison of gene content and genome architecture of Trypanosoma
brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens
with different life cycles and disease pathology, revealed a conserved
core proteome of about 6200 genes in large syntenic polycistronic gene
clusters. Many species-specific genes, especially large surface antigen
families, occur at nonsyntenic chromosome-internal and subtelomeric
regions. Retroelements, structural RNAs, and gene family expansion are
often associated with syntenic discontinuities that-along with gene
divergence, acquisition and loss, and rearrangement within the syntenic
regions-have shaped the genomes of each parasite. Contrary to recent
reports, our analyses reveal no evidence that these species are
descended from an ancestor that contained a photosynthetic endosymbiont.
PMID: 16020725
TITLE: The Genome Sequence of Trypanosoma cruzi, Etiologic Agent of Chagas
Disease.
AUTHORS: Najib M El-Sayed, Peter J Myler, Daniella C Bartholomeu, Daniel
Nilsson, Gautam Aggarwal, Anh-Nhi Tran, Elodie Ghedin, Elizabeth A Worthey,
Arthur L Delcher, Gaëlle Blandin, Scott J Westenberger, Elisabet Caler,
Gustavo C Cerqueira, Carole Branche, Brian Haas, Atashi Anupama, Erik Arner,
Lena Aslund, Philip Attipoe, Esteban Bontempi, Frédéric Bringaud, Peter
Burton, Eithon Cadag, David A Campbell, Mark Carrington, Jonathan Crabtree,
Hamid Darban, Jose Franco da Silveira, Pieter de Jong, Kimberly Edwards, Paul T
Englund, Gholam Fazelina, Tamara Feldblyum, Marcela Ferella, Alberto Carlos
Frasch, Keith Gull, David Horn, Lihua Hou, Yiting Huang, Ellen Kindlund,
Michele Klingbeil, Sindy Kluge, Hean Koo, Daniela Lacerda, Mariano J Levin,
Hernan Lorenzi, Tin Louie, Carlos Renato Machado, Richard McCulloch, Alan
McKenna, Yumi Mizuno, Jeremy C Mottram, Siri Nelson, Stephen Ochaya, Kazutoyo
Osoegawa, Grace Pai, Marilyn Parsons, Martin Pentony, Ulf Pettersson, Mihai
Pop, Jose Luis Ramirez, Joel Rinta, Laura Robertson, Steven L Salzberg, Daniel
O Sanchez, Amber Seyler, Reuben Sharma, Jyoti Shetty, Anjana J Simpson, Ellen
Sisk, Martti T Tammi, Rick Tarleton, Santuza Teixeira, Susan Van Aken, Christy
Vogt, Pauline N Ward, Bill Wickstead, Jennifer Wortman, Owen White, Claire M
Fraser, Kenneth D Stuart, Björn Andersson
AFFILIATION: Department of Parasite Genomics, The Institute for Genomic
Research, Rockville, MD 20850, USA.
REFERENCE: Science 2005 Jul 309(5733):409-15
Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi
revealed that the diploid genome contains a predicted 22,570 proteins
encoded by genes, of which 12,570 represent allelic pairs. Over 50% of
the genome consists of repeated sequences, such as retrotransposons and
genes for large families of surface molecules, which include trans-
sialidases, mucins, gp63s, and a large novel family (>1300 copies) of
mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi
, T. brucei, and Leishmania major (Tritryp) genomes imply differences
from other eukaryotes in DNA repair and initiation of replication and
reflect their unusual mitochondrial DNA. Although the Tritryp lack
several classes of signaling molecules, their kinomes contain a large
and diverse set of protein kinases and phosphatases; their size and
diversity imply previously unknown interactions and regulatory processes
, which may be targets for intervention.
PMID: 16008131
TITLE: A review of natural products with antileishmanial activity.
AUTHORS: L G Rocha, J R G S Almeida, R O Macêdo, J M Barbosa-Filho
AFFILIATION: Departamento de Microbiologia e Parasitologia, Universidade Federal
do Rio Grande do Norte, 59000-000 Natal, RN, Brazil.
REFERENCE: Phytomedicine 2005 Jun 12(6-7):514-35
Infections caused by protozoa of the genus Leishmania are a major
worldwide health problem, with high endemicity in developing countries.
The incidence of the disease has increased since the emergence of AIDS.
In the absence of a vaccine, there is an urgent need for effective drugs
to replace/supplement those in current use. The plant kingdom is
undoubtedly valuable as a source of new medicinal agents. The present
work constitutes a review of the literature on plant extracts and
chemically defined molecules of natural origin showing antileishmanial
activity. The review refers to 101 plants, their families, and
geographical distribution, the parts utilized, the type of extract and
the organism tested. It also includes 288 compounds isolated from higher
plants and microorganisms, classified into appropriate chemical groups
. Some aspects of recent antileishmanial-activity-directed research on
natural products are discussed.
PMID: 15902687
TITLE: Regulation of the Leishmania-induced innate inflammatory response by the
protein tyrosine phosphatase SHP-1.
AUTHORS: Geneviève Forget, Claudine Matte, Katherine A Siminovitch, Serge
Rivest, Philippe Pouliot, Martin Olivier
AFFILIATION: Centre de Recherche en Infectiologie, Centre Hospitalier
Universitaire de Québec, Pavillon CHUL, Université Laval, Ste-Foy, Canada.
REFERENCE: Eur J Immunol 2005 Jun 35(6):1906-17
Modulation of the phagocyte protein tyrosine phosphatase (PTP) SHP-1 by
the parasite Leishmania favors its survival and propagation within its
mammalian host. In vivo, the absence of SHP-1 leads to virtually absent
footpad swelling, accompanied by enhanced inducible nitric oxide
synthase expression. In this study, using an air pouch model, we show
that viable motheaten SHP-1-deficient mice harbored a stronger
inflammatory response against Leishmania infection than wild-type mice.
This response was portrayed by higher pro-inflammatory cytokine (TNF-
alpha, IL-1beta and IL-6) expression and secretion and by greater
chemokine and chemokine receptor expression. These inflammatory
molecules were probably responsible for the stronger cellular
recruitment, mainly of neutrophils, seen at the site of infection in
viable motheaten mice within 6 h post inoculation. We also provide
strong evidence that protein tyrosine phosphatases in general, and SHP-1
in particular, are important regulators of chemokine gene expression.
Overall, this study suggests that the ability of Leishmania to induce
SHP-1 activity in its host allows the taming of an otherwise strong
innate inflammatory response that would be detrimental for its survival
and progression.
PMID: 16022379
TITLE: [Leishmania: role of P glycoprotein in drug resistance and reversion
strategies]
AUTHORS: Edison J Osorio, Sara M Robledo, Gabriel J Arango, Carlos E Muskus
AFFILIATION: Grupo de Investigación en Sustancias Bioactivas, Facultad de
QuÃmica Farmacéutica, Corporación de PatologÃas Tropicales, Universidad de
Antioquia, MedellÃn, Colombia.
REFERENCE: Biomedica 2005 Jun 25(2):242-60
Protozoan parasites are important causative agents of morbidity and
mortality throughout the world--a problem further complicated by the
emergence of drug resistance in these parasites. Mechanisms of drug
resistance include the following: decreased uptake of the drug into the
cell, loss of drug activation, alterations in the drug target, and over-
expression of a well-known multiple drug transporter proteins. In this
review, two critical components of resistance are stressed: (1) the role
of ATP binding cassette proteins, such as P-glycoproteins, in mediating
drug resistance in Leishmania and other protozoans, followed by
development of cross-resistance to many structurally and functionally
unrelated drugs, and (2) some concepts concerning the reversal mechanism
of multidrug resistance by drugs and natural products. Several
modulators or chemosensitizers alter the capacity of P-glycoproteins to
maintain subtoxic intracellular drug concentrations. Calcium channel
blockers such as verapamil act in this mode; however, high
concentrations are required for an efficient and effective inhibition
and, in addition, produce undesirable side effects. The discovery of new
, natural product modulators of P-glycoproteins is stressed. This
category of modulators offer potentially improved efficacy and lowered
toxicity for the mammalian host.
PMID: 16022381
TITLE: [Validation of PCR as a tool for the detection of Leishmania (Vianna)
spp. parasites in the Lutzomyia (Diptera: Psychodidae) vector]
AUTHORS: Erika SantamarÃa, Nubia Ponce, Concepción Puerta, Cristina Ferro
AFFILIATION: Laboratorio de EntomologÃa, Subdirección de Investigación,
Instituto Nacional de Salud, Bogotá, DC, Colombia.
REFERENCE: Biomedica 2005 Jun 25(2):271-9
INTRODUCTION: The applicability of the polymerase chain reaction (PCR)
was evaluated for the detection and identification of parasites in sand
fly vectors and thereby precluding the necessity of dissecting them. DNA
was extracted from individual, laboratory infected sand flies, and
subjected to PCR amplification using specific B1 and B2 primers for
parasites of the Leishmania (Viannia) subgenus. METHODOLOGY: The
sensitivity and specificity of the PCR primers were defined by means of
serial dilutions of a Leishmania culture. Pooled samples of 1 to 5
sandflies were examined in association with the parasite dilutions to
determine the point at which sensitivity became reduced. Experimentally
infected sand flies were used to compare the sensitivity of the PCR with
sand fly dissection and searching for flagellated parasites by
microscopic examination. RESULTS: As few as a single parasite was
detected, and the sensitivity remained unaltered up to 3 female sand
flies per pool. Detection rates were 33% for the traditional technique
and 33.3% for PCR. The B1 and B2 primers were confirmed as specific for
Leishmania (Viannia) parasites. CONCLUSION: The demonstrably high
sensitivity and specificity of PCR warrant the use of PCR in assessing
natural infection rates of Leishmania (Viannia) in field populations of
sand fly vectors.
PMID: 16013255
TITLE: [Cloning and sequence analysis of ITS gene of Leishmania donovani
isolates from different epidemic foci in China]
AUTHORS: Yu Tian, Jianping Chen
AFFILIATION: Department of Parasitology, School of Preclinical and Forensic
Medicine, Sichuan University, Chengdu 610041, China.
REFERENCE: Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2005 Jun 22(3):540-4
This study was directed to determine the nucleotide sequence of the ITS
(internal transcribed spacer) gene of Leishmania Donovani isolates from
desert foci (L. d XJ771), hill foci (L. d SC10) and plain foci (L. d
SD2), and to find out the differences of the sequences of ITS gene among
these three isolates. The specific ITS fragments from nuclear DNA of
three Leishmania isolates were amplified by PCR, cloned into PMD18-T
vector, and then sequenced by the dideoxy chain termination method.
Sequence analysis showed that the amplified DNA fragments of the three
isolates were 1 086 bp (L. d XJ771), 1 027 bp (L. d SC10) and 1 028 bp (
L. d SD2). There were obvious sequence differences among L. d XJ771, L.
d SC10 and L. d SD2. The differences between L. d XJ771 (desert foci
isolate) and L. d SC10 (hill foci isolate) were less than the
differences between L. d XJ771 (desert foci isolate ) and L. d SD2. (
plain foci isolate).
REQUEST: [ sand fly ]
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REQUEST: [ sandfly ]
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