[leish-l] Fwd: Articles found by RefScout 20/07/05 - 29/2005

jeffreyj at usp.br jeffreyj at usp.br
Thu Jul 21 09:38:27 BRT 2005

----- Forwarded message from info at refscout.com -----
    Date: Wed, 20 Jul 2005 04:14:59
    From: info at refscout.com


Have a look at our new tool, the RefScout‘s PDF-Manager (PDFM)! The RefScout‘s
PDFM will revolutionize your life with PDF files!

Simply let your PDF files be organized by the RefScout‘s PDFM in a table and get
direct link to your local copy. In addition, the RefScout‘s PDFM will alert you
each time the NLM PubMed updates information concerning your specific
Get your free 2 months trial version now at RefScout’s PDF-Manager.

This is RefScout-Newsletter 29/2005.

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

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,

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 Química e Bioquímica, Departmento de Química e
Bioquímica, 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 

PMID: 16020131


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 

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.


 The following references are revised files and are brought to you in accordance
to license agreement with the NLM.


PMID: 15817202

TITLE: Osteolytic osteomyelitis associated with visceral leishmaniasis in a

AUTHORS: Alda Izabel de Souza, Raquel Soares Juliano, Tatiana Scanoni Gomes,
Soraia de Araujo Diniz, Alan Maia Borges, Wagner Luiz Tafuri, Renato Lima

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

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

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

AUTHORS: Edison J Osorio, Sara M Robledo, Gabriel J Arango, Carlos E Muskus

AFFILIATION: Grupo de Investigación en Sustancias Bioactivas, Facultad de
Química Farmacéutica, Corporación de Patologías Tropicales, Universidad de
Antioquia, Medellín, 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 Santamaría, Nubia Ponce, Concepción Puerta, Cristina Ferro

AFFILIATION: Laboratorio de Entomología, 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 ]

(1 article matches this request. 1 article matching other requests removed)

REQUEST: [ sandfly ]

(0 articles match this request)

You receive this email because you requested RefScout&#174;'s literature
If you would like to change or add requests, please go to your user

If you can't read our newsletter, please resend newsletter back to us to
info at refscout.com, including information
about your operating system and mail client software you use, and we will do
best to solve the problem.

If you would like to be removed from RefScout&#174;'s literature service, please
press the
remove button.


----- End forwarded message -----

More information about the Leish-l mailing list