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This is RefScout-Newsletter 45/2004.






REQUEST: [ leishmaniasis ]

(13 articles match this request. 1 article matching other requests removed)



PMID: 15511622
 

TITLE: Hematologic problems in immigrants from Southeast Asia.

AUTHORS: Michael R Jeng, Elliott Vichinsky

AFFILIATION: Department of Pediatrics, Stanford University School of Medicine,
300 Pasteur Drive, Room S-304, Stanford, CA 94305-5208, USA.

REFERENCE: Hematol Oncol Clin North Am 2004 Dec 18(6):1405-22

An increasing number of Southeast Asian immigrants have come to North 
America. Physicians who care for this population should be aware of the 
high prevalence of hematologic disorders and develop an approach to 
their diagnosis and management. Malaria and the hematologic sequelae, 
glucose-6-phophate dehydrogenase deficiency, the thalassemia syndromes, 
Southeast Asian ovalocytosis, visceral leishmaniasis, HIV infection, and
 iron-deficiency anemia, all of which may pertain to these patients, are
 reviewed in this article.








PMID: 15517072
 

TITLE: Leishmania infantum heat shock protein 83 for the serodiagnosis of
tegumentary leishmaniasis.

AUTHORS: B J Celeste, S O Angel, L G M Castro, M Gidlund, H Goto

AFFILIATION: Laboratório de Soroepidemiologia e Imunobiologia, Instituto de
Medicina Tropical de São Paulo, Universidade de São Paulo.

REFERENCE: Braz J Med Biol Res 2004 Nov 37(11):1591-3

The serologic assay is an important tool in the diagnosis of 
leishmaniasis. One of the most commonly used tests is enzyme-linked 
immunosorbent assay (ELISA). Since total Leishmania promastigotes are 
used as antigen in the routine assay, false-positive reactions are 
frequent due to cross-reaction with sera from other diseases, mainly 
Chagas' disease. Therefore, an antigen that determines less cross-
reactivity has been pursued for the serodiagnosis of leishmaniasis. In 
the present study we analyzed the use of recombinant Leishmania infantum
 heat shock protein (Hsp) 83 in ELISA for the serodiagnosis of cutaneous
 (N = 12) and mucocutaneous leishmaniasis (N = 14) and we observed the 
presence of anti-L. infantum Hsp 83 antibodies in all samples as well as
 anti-Leishmania total antigen antibodies. When cross-reactivity was 
tested, chronic Chagas' disease patients (N = 10) did not show any 
reactivity. Therefore, we consider this L. infantum Hsp 83 to be a good 
antigen for routine use for serodiagnosis of tegumentary leishmaniasis.




PMID: 15514349
 

TITLE: Integrating evidence based medicine into routine clinical practice: seven
years' experience at the Hospital for Tropical Diseases, London.

AUTHORS: Diana Lockwood, Margaret Armstrong, Alison Grant

AFFILIATION: Hospital for Tropical Diseases, University College London Hospitals
NHS Trust, Mortimer Market Centre, London WC1E 6AU.

REFERENCE: BMJ 2004 Oct 329(7473):1020-3

PROBLEM: Introduction and evaluation of evidence based medicine (EBM) 
into routine hospital practice. STRATEGY FOR CHANGE: Routine EBM 
meetings introduced in 1997. DESIGN: Review of outcomes of meetings from
 1997 to 2004, focusing on their effect on clinical practice. SETTING: 
Referral centre for tropical and domestic infectious diseases. KEY 
MEASURE FOR IMPROVEMENT: Outcome of meetings, classified as resulting in
 a change in practice; confirmation or clarification of existing 
practice; identification of a need for more evidence; and outcome 
unclear. EFFECTS OF CHANGE: Examples include a change from inpatient to 
day case treatment of New World cutaneous leishmaniasis; development of 
guidelines on the treatment of coinfection with visceral leishmaniasis 
and HIV; and identification of the need for more data on the efficacy 
and toxicity of atovaquone-proguanil (Malarone) compared with quinine 
plus sulfadoxine-pyrimethamine (Fansidar) in the treatment of 
uncomplicated falciparum malaria, which resulted in a clinical trial 
being set up. LESSONS LEARNT: Incorporation of EBM meetings into our 
routine practice has resulted in treatment guidelines being more closely
 based on published evidence and improvements to care of patients. 
Written summaries of the meetings are important to facilitate change.




PMID: 15516633
 

TITLE: Short report: fluorescent leishmania: application to anti-leishmanial
drug testing.

AUTHORS: Neeloo Singh, Anuradha Dube

AFFILIATION: Division of Biochemistry and Division of Parasitology, Central Drug
Research Institute, Lucknow, India.

REFERENCE: Am J Trop Med Hyg 2004 Oct 71(4):400-2

Classic techniques for detecting the susceptibility of Leishmania to 
different drugs are time-consuming, laborious, and require the use of 
macrophages. The use of flow cytometry for monitoring Leishmania 
susceptibility to drugs is beginning to be implemented. Using green 
fluorescent protein (GFP), we have improved and simplified the screening
 procedure. We introduced a GFP marker into field strains of Leishmania 
causing kala-azar (visceral leishmaniasis) and explored the suitability 
of transgenic L. donovani promastigotes that constitutively express GFP 
in their cytoplasm as target cells for in vitro screening of anti-
leishmanial drugs.




PMID: 15509428
 

TITLE: The sandflies (Diptera: Psychodidae) in the Turkish province of Hatay:
some possible vectors of the parasites causing human cutaneous leishmaniasis.

AUTHORS: M Yaman, Y Ozbel

AFFILIATION: Mustafa Kemal University, Faculty of Veterinary Medicine,
Department of Parasitology, 31040 - Antakya, Hatay, Turkey.

REFERENCE: Ann Trop Med Parasitol 2004 Oct 98(7):741-50

The province of Hatay, which lies on the Mediterranean coast in south-
eastern Turkey, forms an important endemic area for human cutaneous 
leishmaniasis (HCL). Between the June and November of 2001, the 
sandflies in eight areas of the province, Erzin, Dortyol, Iskenderun, 
Kirikhan, Antakya, Samandag, Altinozu and Yayladagi, were surveyed, 
using sticky-paper traps placed in goat, sheep, cow or chicken sheds 
close to houses. Although 217 of the 998 sandflies caught belonged to 
the genus Sergentomyia, the rest were of Phlebotomus species, including 
some species that, elsewhere, are known to act as vectors of the 
parasites causing HCL. The Sergentomyia caught were either S. theodori (
59.9%) or S. dentata (40.1%). Most of the Phlebotomus were P. sergenti (
60.8%) but P. papatasi (18.8%), P. syriacus (9.3%), P. neglectus (5.1
%), P. tobbi (2.7%), P. simici (2.2%), P. alexandri (0.9%) and P. 
kyreniae (0.1%) were also identified (the latter three species for the 
first time in Hatay province). The identification of the main vector 
species of sandfly in the province is complicated because it is still 
uncertain which Leishmania species cause(s) the local HCL. It seems 
likely, however, that P. sergenti is the main vector in Antakya, 
Iskenderun, Dortyol, Erzin and Kirikhan. In areas such as Altinozu and 
Yayladagi, where, although P. sergenti is very rare or absent, HCL cases
 still occur each year, other species, such as the relatively abundant P
. papatasi and P. syriacus, may be the main vectors.




PMID: 15509421
 

TITLE: Diagnosis of visceral leishmaniasis: the sensitivities and specificities
of traditional methods and a nested PCR assay.

AUTHORS: S Gatti, M Gramegna, C Klersy, S Madama, A Bruno, R Maserati, A M
Bernuzzi, C Cevini, M Scaglia

AFFILIATION: Laboratory of Parasitology, Virology Service, IRCCS Policlinico San
Matteo, Viale Taramelli, 5, 27100 Pavia, Italy.

REFERENCE: Ann Trop Med Parasitol 2004 Oct 98(7):667-76

In the present study, 67 patients suspected to be cases of visceral 
leishmaniasis (VL) were each checked for leishmanial infection by the 
microscopical evaluation of various biological specimens, in-vitro 
culture, serology and an assay based on nested PCR. Most (35) of the 
subjects were immunocompetent (IC) but 32 were immunodeficient (ID) as 
the result of HIV infection (18 cases), treatment to prevent 
transplanted organs being rejected (six) or haematological malignancies
 (eight). Forty-one (61.2%) of the subjects (19 IC subjects, 12 HIV-
positive patients, four transplant patients and six patients with 
malignancies) were considered true cases of VL. For the IC subjects, 
only the production and microscopical examination of 
leucocytoconcentrates and cultures of Buffy coats gave sensitivities of
 <80%, the results of the other methods showing higher sensitivities
 and almost perfect agreement with the 'gold-standard' diagnoses. For 
the ID subjects, however, only the serological tests and the PCR gave 
reasonable sensitivities (of >80%). For the initial diagnosis of 
leishmaniasis in ID patients, IFAT and western blots may be useful, as, 
among the present ID patients, they gave sensitivities (of 80.9% and 88.
2%, respectively) that were almost as high as that for the PCR, and 
specificities of 100%. In the diagnosis of VL in either IC or ID 
patients, the assay based on a nested PCR appeared to be particularly 
reliable, with sensitivities of 88.9% and 95.2%, respectively, and a 
specificity of 100% in both groups of patients. The testing of bone-
marrow aspirates by PCR revealed very few VL cases who were not found 
positive when samples of their peripheral blood were checked in the same
 assay. For both IC and ID subjects therefore, the use of the PCR-based 
method to test samples of peripheral blood (which can be collected much 
more easily than bone-marrow aspirates and with much less pain for the 
subject) is recommended.








PMID: 15510962
 

TITLE: Visceral leishmaniasis in a non-endemic area of India.

AUTHORS: A Sud, N Varma, R K Marwaha, F M Patel, A Trehan, S Singh, S Varma

AFFILIATION: Department of Internal Medicine, Postgraduate Institute of Medical
Education and Research, Chandigarh, India. asud at doctor.com

REFERENCE: Trop Doct 2004 Oct 34(4):247-9

The study included 57 patients with visceral leishmaniasis. The average 
duration of symptoms was 3.8 +/- 3.55 months and pancytopenia was the 
commonest haematological abnormality. The parasite load directly 
correlated with the degree of anaemia at presentation (P=0.03). Splenic 
regression took 9.58 +/- 4.5 days and haematological parameters 
recovered in 14.5 +/- 9.07 days. There were five deaths over the five-
year study duration. Leishmaniasis was not the first diagnosis in 14 
patients, of whom eight were residents of non-endemic regions. Diagnosis
 was achieved in 13.5 days in these patients, compared to 4.5 days in 
patients where leishmaniasis was suspected at the outset.




PMID: 15489554
 

TITLE: Epidemiological, clinical & pharmacological study of
antimony-resistant visceral leishmaniasis in Bihar, India.

AUTHORS: C P Thakur, S Narayan, A Ranjan

AFFILIATION: Balaji Utthan Sansthan & Rajendra Memorial Research Institute
of Medical Sciences, Patna, India. cpthakur at sancharnet.in

REFERENCE: Indian J Med Res 2004 Sep 120(3):166-72

BACKGROUND & OBJECTIVES: Sodium antimony gluconate (SAG) is reported
 to be losing its efficacy in Bihar as a first line drug for treatment 
of visceral leishmaniasis (VL). Concerned with the increasing incidence 
of antimony-resistant VL patients in Bihar, we undertook an 
epidemiological, clinical and pharmacological study to formulate a 
scientific basis for choosing a suitable first line drug for VL. METHODS
: Consecutive, fresh and parasitologically confirmed patients of VL from
 different geographical areas of Bihar were considered for inclusion in 
the study. Parasites isolated from patients were tested in vitro to 
assess their response to sodium antimony gluconate (SAG) to 20 microg/ml
, response to 20 mg/kg of SAG for 5 days in experimentally induced VL in
 BALB/c mice from those isolates, and response to SAG in patients 
treated with SAG for 28 days. Similarly response in culture (1 microg/ml
) to amphotericin B (AMB) of all 282 isolates, (1 mg/kg body wt for 20 
days) in patients and infected BALB/c mice (1 mg/kg body wt for 5 days) 
was determined. Antimony levels of plasma were determined at 2, 8 and 24
 h after intramuscular injection of SAG. Patients unwilling for SAG 
treatment or relapsed after SAG treatment and withdrawn from SAG group 
because of toxicity were treated with AMB. Plasma antimony levels were 
estimated by atomic absorption spectrometer. RESULTS: Though antimony 
sensitive and resistant patient were distributed in all 14 districts of 
Bihar studied, there was a significant variation from district to 
district. Of the 123 patients included in the SAG treatment group, 19 
were withdrawn due to development of toxicity and 2 died; 178 patients 
were treated with AMB. No patient in AMB group developed any toxicity or
 died. Only 47 (46%) of 102 patients, 106 (37.6%) of 282 infected 
macrophages, 90 (52.9%) of 170 experimental infections were cured with 
SAG. Mc Nemar's test on paired comparisons showed statistical 
significance difference (P<0.01) between infected macrophage and 
experimental infection. AMB cured all patients, infected mice and 
cleared parasites from all isolates. INTERPRETATION & CONCLUSION: 
Antimony resistant strains of L. donovani were wide spread over 
different geographical areas in Bihar. SAG cured lesser percentage of VL
 cases clinically compared to AMB and should be replaced by AMB as a 
first line drug.




PMID: 15358255
 

TITLE: Cysteine peptidases as virulence factors of Leishmania.

AUTHORS: Jeremy C Mottram, Graham H Coombs, James Alexander

AFFILIATION: Wellcome Centre for Molecular Parasitology, University of Glasgow,
Glasgow G12 8QQ, UK. j.mottram at udcf.gla.ac.uk

REFERENCE: Curr Opin Microbiol 2004 Aug 7(4):375-81

Leishmania mexicana amastigotes are particularly rich in cysteine 
peptidases (CPs), which play important roles in facilitating the 
survival and growth of the parasites in mammals. The importance of the 
CPs as virulence factors and their potential as drug targets and vaccine
 candidates has been investigated extensively. Recent years, however, 
have heralded advances in our knowledge and understanding of leishmanial
 CPs on two fronts. Firstly, genome analysis has revealed the great 
diversity of CPs, and, secondly, the ways in which the most widely 
studied CPs, designated CPB, influence the interaction between parasite 
and mammalian host have been elucidated. These topics are the focus of 
this review.




********************************************************************************************************************

 The following references are revised files and are brought to you in accordance
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PMID: 14651635
 

TITLE: Heterologous expression of a mammalian protein tyrosine phosphatase gene
in Leishmania: effect on differentiation.

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.




PMID: 15228244
 

TITLE: Wild and synanthropic hosts of Leishmania (Viannia) braziliensis in the
endemic cutaneous leishmaniasis locality of Amaraji, Pernambuco State, Brazil.

AUTHORS: Sinval P Brandão-Filho, Maria E Brito, Francisco G Carvalho, Edna A
Ishikawa, Elisa Cupolillo, Lucile Floeter-Winter, Jeffrey J Shaw

AFFILIATION: Centro de Pesquisas Aggeu Magalhães, FIOCRUZ, Av. Moraes Rego,
S/N, Recife 50670-420, Pernambuco, Brazil.

REFERENCE: Trans R Soc Trop Med Hyg 2003 May-Jun 97(3):291-6

Evidence of Leishmania infection was found in small mammals captured 
between 1996 and 2000 in the Amaraji region, Pernambuco State, Brazil. 
The kDNA polymerase chain reaction (PCR), using primers specific for 
subgenus L. (Viannia), was positive for 43/153 water rats (Nectomys 
squamipes), 13/81 black rats (Rattus rattus), 15/103 grass mice (Bolomys
 lasiurus), 1/14 marsh mice (Holochilus scieurus), 2/50 field mice (
Akodon arviculoides), 2/12 woolly opossums (Marmosa sp.), and 5/37 
common opossums (Didelphis albiventris). This same kDNA PCR was positive
 for 12/61 dog and 8/58 horse skin samples. In paired PCR tests of 203 
small mammals, 18.7% were positive with the kDNA primers and 18.2% with 
rDNA primers. Amastigotes were seen in 26/460 and L. (V.) braziliensis 
was isolated from 5 grass mice and 1 black rat. We concluded that small 
mammals, particularly rodents, are infected with parasites of the 
subgenus L. (Viannia). The isolation of L. (V.) braziliensis zymodeme 
IOC/Z74 from 6 rodents and the fact that all the other described L. (
Viannia) species that commonly infect humans have never been found in 
rodents or marsupials leads us to suggest that the positive PCRs 
indicate infections of L. (V.) braziliensis. The isolation of zymodeme 
IOC/Z74 from humans reinforces our hypothesis that small, ground-loving 
mammals, such as rodents are the primary reservoirs of L. (V.) 
braziliensis.








PMID: 11544330
 

TITLE: Sodium stibogluconate is a potent inhibitor of protein tyrosine
phosphatases and augments cytokine responses in hemopoietic cell lines.

AUTHORS: M K Pathak, T Yi

AFFILIATION: Department of Cancer Biology, Lerner Research Institute, Cleveland
Clinic Foundation, Cleveland, OH 44195, USA.

REFERENCE: J Immunol 2001 Sep 167(6):3391-7

Using in vitro protein tyrosine phosphatase (PTPase) assays, we found 
that sodium stibogluconate, a drug used in treatment of leishmaniasis, 
is a potent inhibitor of PTPases Src homology PTPase1 (SHP-1), SHP-2, 
and PTP1B but not the dual-specificity phosphatase mitogen-activated 
protein kinase phosphatase 1. Sodium stibogluconate inhibited 99% of SHP
-1 activity at 10 micrograms/ml, a therapeutic concentration of the drug
 for leishmaniasis. Similar degrees of inhibition of SHP-2 and PTP1B 
required 100 micrograms/ml sodium stibogluconate, demonstrating 
differential sensitivities of PTPases to the inhibitor. The drug 
appeared to target the SHP-1 domain because it showed similar in vitro 
inhibition of SHP-1 and a mutant protein containing the SHP-1 PTPase 
domain alone. Moreover, it forms a stable complex with the PTPase: in 
vitro inhibition of SHP-1 by the drug was not removed by a washing 
process effective in relieving the inhibition of SHP-1 by the reversible
 inhibitor suramin. The inhibition of cellular PTPases by the drug was 
suggested by its rapid induction of tyrosine phosphorylation of cellular
 proteins in Baf3 cells and its augmentation of IL-3-induced Janus 
family kinase 2/Stat5 tyrosine phosphorylation and proliferation of Baf3
 cells. The augmentation of the opposite effects of GM-CSF and IFN-alpha
 on TF-1 cell growth by the drug indicated its broad activities in the 
signaling of various cytokines. These data represent the first evidence 
that sodium stibogluconate inhibits PTPases and augments cytokine 
responses. Our results provide novel insights into the pharmacological 
effects of the drug and suggest potential new therapeutic applications.




REQUEST: [ leishmania ]

(15 articles match this request. 5 articles matching other requests removed)



PMID: 15342784
 

TITLE: SMP-1, a Member of a New Family of Small Myristoylated Proteins in
Kinetoplastid Parasites, Is Targeted to the Flagellum Membrane in Leishmania.

AUTHORS: Dedreia Tull, James E Vince, Judy M Callaghan, Thomas Naderer, Tim
Spurck, Geoffrey I McFadden, Graeme Currie, Kris Ferguson, Antony Bacic,
Malcolm J McConville

AFFILIATION: Department of Biochemistry and Molecular Biology, University of
Melbourne, Royal Parade, Parkville, Victoria 3010, Australia.

REFERENCE: Mol Biol Cell 2004 Nov 15(11):4775-86

The mechanisms by which proteins are targeted to the membrane of 
eukaryotic flagella and cilia are largely uncharacterized. We have 
identified a new family of small myristoylated proteins (SMPs) that are 
present in Leishmania spp and related trypanosomatid parasites. One of 
these proteins, termed SMP-1, is targeted to the Leishmania flagellum. 
SMP-1 is myristoylated and palmitoylated in vivo, and mutation of Gly-2 
and Cys-3 residues showed that both fatty acids are required for 
flagellar localization. SMP-1 is associated with detergent-resistant 
membranes based on its recovery in the buoyant fraction after Triton X-
100 extraction and sucrose density centrifugation and coextraction with 
the major surface glycolipids in Triton X-114. However, the flagellar 
localization of SMP-1 was not affected when sterol biosynthesis and the 
properties of detergent-resistant membranes were perturbed with 
ketoconazole. Remarkably, treatment of Leishmania with ketoconazole and 
myriocin (an inhibitor of sphingolipid biosynthesis) also had no affect 
on SMP-1 localization, despite causing the massive distension of the 
flagellum membrane and the partial or complete loss of internal axoneme 
and paraflagellar rod structures, respectively. These data suggest that 
flagellar membrane targeting of SMP-1 is not dependent on axonemal 
structures and that alterations in flagellar membrane lipid composition 
disrupt axoneme extension.




PMID: 15516635
 

TITLE: Protection of c3heb/fej mice against leishmania amazonensis challenge
after previous leishmania major infection.

AUTHORS: Yannick Vanloubbeeck, Douglas E Jones

AFFILIATION: Department of Veterinary Pathology, College of Veterinary Medicine,
Iowa State University, Ames, Iowa.

REFERENCE: Am J Trop Med Hyg 2004 Oct 71(4):407-11

The Th1 response elicited in mice infected with Leishmania major has 
been used as a model to characterize cellular immune defects associated 
with L. amazonensis infection. However, it is not known if the immune 
response associated with the infection by virulent L. major parasites 
can promote resistance to a subsequent L. amazonensis infection. Our 
data demonstrate that C3HeB/FeJ mice infected subcutaneously with 
virulent L. major are resistant to an L. amazonensis challenge. The 
healing phenotype is characterized by a Th1 response as measured by 
increased production of interferon-gamma and low levels of interleukin-4
 in the draining lymph node. Together, this indicates that the Th1 
response associated with L. major infection can promote resistance to L
. amazonensis infection and that it can be used as a tool to study the 
immune defects associated with L. amazonensis infection.




PMID: 15507202
 

TITLE: Flypaper for parasites.

AUTHORS: Stephen M Beverley, Deborah E Dobson

AFFILIATION: Department of Molecular Microbiology, Washington University Medical
School, 660 S. Euclid Avenue, St. Louis, MO 63110 USA.

REFERENCE: Cell 2004 Oct 119(3):311-2

In this issue, describe the identification of an insect galectin as the 
receptor for the stage-specific Leishmania adhesin lipophosphoglycan (
LPG). This interaction is critical for parasite survival in the midgut 
of its sand fly vector. The results open new avenues for studies of 
insect immunity, transmission binding vaccines, and host-parasite 
coevolution.




PMID: 15509422
 

TITLE: Identification of Leishmania strains from Jordan.

AUTHORS: E K Saliba, F Pratlong, J P Dedet, N Saleh, S A Khoury, O Y Oumeish, O
Batayneh, R Al-Oran

AFFILIATION: Department of Biotechnology and Genetic Engineering, Philadelphia
University, P.O. Box 1, Amman, 19392, Jordan.

REFERENCE: Ann Trop Med Parasitol 2004 Oct 98(7):677-83

The enzymatic profiles of 22 Jordanian Leishmania isolates obtained from
 humans, Psammomys obesus and Phlebotomus papatasi were determined using
 starch-gel electrophoresis and a 15-enzyme system. Thirteen of the 
isolates were typed as L. major and the other nine, all from 
Mediterranean or sub-Mediterranean regions, as L. tropica. The two 
zymodemes of L. major encountered, MON-26 and MON-103, differed in terms
 of purine nucleoside phosphorylase 2. The MON-26 isolates came from the
 Jordanian plateau whereas those of MON-103 were only collected from the
 Jordan valley. The four zymodemes of L. tropica observed (MON-7, MON-
137, MON-200 and MON-265) were identical for only two of the 15 enzymes 
studied (i.e. isocitrate dehydrogenase and glucose phosphate isomerase
), confirming the high level of enzymatic polymorphism of L. tropica. So
 far, MON-200 and MON-265 have only been found in Jordan.








PMID: 15511274
 

TITLE: Ginseng modulates the immune response by induction of interleukin-12
production.

AUTHORS: Maria Waldorff Larsen, Claus Moser, Niels Høiby, Zhijun Song, Arsalan
Kharazmi

AFFILIATION: Department of Clinical Microbiology, University Hospital
(Rigshospitalet), afsnit 7602, Copenhagen, Denmark.

REFERENCE: APMIS 2004 Jun 112(6):369-73

Larsen MW, Moser C, Hoiby N, Song Z, Kharazmi A. Ginseng modulates the 
immune response by induction of interleukin-12 production. APMIS 112;
2004:369-73.In infections with intracellular microorganisms such as 
mycobacteria and Leishmania parasites as well as certain extracellular 
chronic infections such as Pseudomonas aeruginosa a Th1 response with 
activation of macrophages is desirable. Several studies indicate that 
such a response is associated with better recovery from infection, 
improved course of the chronic infection, and higher survival rate. In 
Th1 responses there is increased interferon-gamma (IFN-gamma) and 
interleukin-12 (IL-12) production, whereas that of interleukin-10 (IL-10
) is decreased. The present study indicated that Ginseng modulation of 
stimulated peripheral blood mononuclear cells (PBMC) results in a higher
 IL-12 production. The enhanced IL-12 production could induce a stronger
 Th1 response, resulting in better protection against infection with a 
variety of pathogens.




PMID: 15515964
 

TITLE: Comparative effect of ion calcium and magnesium in the activation and
infection of the murine macrophage by Leishmania major.

AUTHORS: Henrique Lanza, Sandra R Afonso-Cardoso, Adriano G Silva, Danielle R
Napolitano, Foued S Espíndola, Janethe D O Pena, Maria A Souza

AFFILIATION: Laboratório de Imunologia, Instituto de Ciências Biomédicas,
Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.

REFERENCE: Biol Res 2004  37(3):385-93

Amastigotes of Leishmania major have a great ability to evade 
destruction in host cells. This study investigated the activation in 
resident, inflammatory macrophages and J774 cells in vitro treated with 
lipopolysaccharide (LPS), soluble Leishmania antigen (SLA), calcium 
ionophore (CaI) and magnesium (Mg2+) alone or combined. An increase in 
nitric oxide (NO) production was observed in J774 or inflammatory 
macrophages treated with LPS alone or in combination with SLA and CaI. 
The same treatments did not affect the NO release by resident 
macrophages. There was no interference in uptake of L. major but CaI 
decreased intracellular proliferation of the parasite. This study 
demonstrated the importance of CaI in decreasing L. major proliferation 
inside murine macrophages while Mg2+ seemed to increase parasite 
proliferation. These finding may help to understand the events involved 
in host cells' clearance of this pathogen.




PMID: 15515575
 

TITLE: Free light-chain proteinuria and normal renal histopathology and function
in 11 dogs exposed to Lleishmania infantum, Ehrlichia canis, and Bbabesia
canis.

AUTHORS: Ugo Bonfanti, Eric Zini, Emanuele Minetti, Andrea Zatelli

AFFILIATION: Clinica Veterinaria Gran Sasso, Milano, Italy. u.bonfa at flashnet.it

REFERENCE: J Vet Intern Med 2004 Sep-Oct 18(5):618-24

The purpose of this retrospective study was to investigate the 
relationship among proteinuria consisting of immunoglobulin free light 
chains (FLCs), renal histopathologic findings, and routine markers of 
renal function in 11 dogs exposed to Leishmania infantum (n = 8), 
Ehrlichia canis (n = 2), and Babesia canis (n = 1). FLC proteinuria was 
suspected based on identification of a 22- to 27-kDa band by sodium 
dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) and later 
confirmed by immunofixation electrophoresis. SDS-AGE identified an 
isolated band of 22-27 kDa in 8 dogs, whereas the remaining 3 had a 22- 
to 27-kDa band and an additional band of 67-72 kDa. The median urine 
protein-to-urine creatinine ratio was 0.37 (range, 0.11-2.24) and 
increased ratios were found in 6 dogs (54.5%) (reference value, <0.7
). All dogs underwent histologic examination of renal percutaneous 
biopsy specimens and determination of serum creatinine and urea 
concentrations. Tissue samples for light microscopy were stained with 
hematoxylin-eosin, periodic acid-Schiff, Goldners trichrome, and 
methenamine silver. In the study group, the glomerular tufts, mesangium
, tubulointerstitium, and vessels appeared unaffected. The median serum 
creatinine concentration in these 11 dogs was 1.3 mg/dL (range, 0.8-1.5 
mg/dL; reference range, 0.6-1.5 mg/dL), whereas the concentration for 
urea was 28 mg/dL (range, 22-52 mg/dL; reference range, 20-50 mg/dL). 
All dogs had normal renal morphology and had normal serum creatinine and
 urea concentrations, suggesting that immunoglobulin FLC may be detected
 in the urine of dogs exposed to L. infantum, E. canis, and B. canis 
without any apparent structural or functional renal derangement.




PMID: 15482153
 

TITLE: Cutaneous leishmaniasis: current and future management.

AUTHORS: Neill C Hepburn

AFFILIATION: Lincoln County Hospital, Lincoln, LN2 5QY, UK.
Neill.Hepburn at ULH.NHS.UK

REFERENCE: Expert Rev Anti Infect Ther 2003 Dec 1(4):563-70

Leishmaniasis remains a major world health problem that continues to 
increase in incidence. This review considers epidemiology, clinical 
features, diagnosis and current treatment options. Recent developments 
in the treatment of simple cutaneous leishmaniasis are discussed 
followed by speculation about future therapies.




PMID: 15508774
 

TITLE: [Treatment of Acanthamoeba keratitis: standard, problems, and new
approaches]

AUTHORS: Julia Walochnik, Michael Duchêne, Hansjörg Eibl, Horst Aspöck

AFFILIATION: Abteilung fur Medizinische Parasitologie, Klinisches Institut fur
Hygiene und Medizinische Mikrobiologie, Wien, Osterreich.
julia.walochnik at univie.ac.at

REFERENCE: Wien Klin Wochenschr 2003  115 Suppl 3():10-7

Acanthamoeba keratitis is a corneal disease associated predominantly 
with contact lens wear. The occurrence of Acanthamoeba keratitis has 
been rising since 1990 in correlation to the growing number of contact 
lens wearers. To date approximately 2000 cases have been published 
around the world. Due to the complicated diagnostics, the elaborate 
treatment and the usually bad compliance of the patients, Acanthamoeba 
keratitis unfortunately very often takes a serious progression, which 
may lead to serious visual loss and perforating keratoplasty. Today, 
local treatment with a combination of polyhexamethylene biguanide (PHMB
) and propamidine isethionate (Brolene) is considered the first line 
therapy for Acanthamoeba keratitis. Alternatively also a combination of 
propamidine and chlorhexidine or neomycine achieves good therapeutic 
results. However, the complicated mode of application consistently 
remains a problem. The intensive local treatment, i.e. hourly 
application of therapeutics during the first three days day and night 
makes hospitalization inevitable. Moreover, sufficient efficacy can not 
always be achieved, and also resistance against propamidine has already 
been observed. Recently propamidine has sometimes been replaced by 
hexamidine, which seems to have a greater cysticidal activity. A new 
path might be struck by the application of alkylphosphocholines. These 
are phosphocholines esterified to aliphatic alcohols. They exhibit in 
vitro and in vivo antineoplastic activity and have been shown to be 
cytotoxic against Leishmania donovani, Trypanosoma cruzi, and Entamoeba 
histolytica. A recent study has demonstrated that particularly 
hexadecylphosphocholine is highly effective also against various strains
 of Acanthamoeba.




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PMID: 11714689
 

TITLE: The Caenorhabditis elegans polarity gene ooc-5 encodes a Torsin-related
protein of the AAA ATPase superfamily.

AUTHORS: S E Basham, L S Rose

AFFILIATION: Section of Molecular and Cellular Biology, University of
California, Davis, CA 95616, USA.

REFERENCE: Development 2001 Nov 128(22):4645-56

The PAR proteins are required for polarity and asymmetric localization 
of cell fate determinants in C. elegans embryos. In addition, several of
 the PAR proteins are conserved and localized asymmetrically in 
polarized cells in Drosophila, Xenopus and mammals. We have previously 
shown that ooc-5 and ooc-3 mutations result in defects in spindle 
orientation and polarity in early C. elegans embryos. In particular, 
mutations in these genes affect the re-establishment of PAR protein 
asymmetry in the P(1) cell of two-cell embryos. We now report that ooc-5
 encodes a putative ATPase of the Clp/Hsp100 and AAA superfamilies of 
proteins, with highest sequence similarity to Torsin proteins; the gene 
for human Torsin A is mutated in individuals with early-onset torsion 
dystonia, a neuromuscular disease. Although Clp/Hsp100 and AAA family 
proteins have roles in diverse cellular activities, many are involved in
 the assembly or disassembly of proteins or protein complexes; thus, OOC
-5 may function as a chaperone. OOC-5 protein co-localizes with a marker
 of the endoplasmic reticulum in all blastomeres of the early C. elegans
 embryo, in a pattern indistinguishable from that of OOC-3 protein. 
Furthermore, OOC-5 localization depends on the normal function of the 
ooc-3 gene. These results suggest that OOC-3 and OOC-5 function in the 
secretion of proteins required for the localization of PAR proteins in 
the P(1) cell, and may have implications for the study of torsion 
dystonia.




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