[Leish-l] Fwd: Articles found by RefScout 2006/03/15 2006/11

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   Date: Wed, 15 Mar 2006 06:03:42
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This is RefScout-Newsletter 11/2006.






REQUEST: [ leishmaniasis ]

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



PMID: 16257024
 

TITLE: Mixed infection with Leishmania (Viannia) braziliensis and Leishmania
(Leishmania) chagasi in a naturally infected dog from Rio de Janeiro, Brazil.

AUTHORS: M F Madeira, A Schubach, T M P Schubach, R S Pacheco, F S Oliveira, S A
Pereira, F B Figueiredo, C Baptista, M C A Marzochi

AFFILIATION: Serviço de Parasitologia, Instituto de Pesquisa Clínica Evandro
Chagas - FIOCRUZ, Av. Brasil 4365, 21045-900 Rio de Janeiro, RJ, Brazil.

REFERENCE: Trans R Soc Trop Med Hyg 2006 May 100(5):442-5

We report here the first case of co-infection with Leishmania (Viannia) 
braziliensis and Leishmania (Leishmania) chagasi in a naturally infected
 dog from Rio de Janeiro, Brazil. Isoenzyme characterisation identified 
the parasites isolated in culture from the cutaneous lesion as L. (V.) 
braziliensis and the isolates from blood and lymph node as L. (L.) 
chagasi. PCR analysis using specific primers followed by molecular 
hybridisation for direct Leishmania species identification in tissue 
fragments confirmed the presence of L. (V.) braziliensis DNA in the 
cutaneous lesion and of L. (L.) chagasi DNA in spleen and popliteal 
lymph node fragments. This report emphasises the importance of 
identification of Leishmania species infecting seropositive dogs in 
endemic areas, and the consequent re-assessment of control and 
epidemiological surveillance measures for the control of leishmaniasis, 
as is the case in Brazil.








PMID: 16414196
 

TITLE: Transmission of Leishmania infantum via blood transfusion in dogs:
Potential for infection and importance of clinical factors.

AUTHORS: Eloisa de Freitas, Maria Norma Melo, Adriane Pimenta da Costa-Val,
Marilene Suzan Marques Michalick

AFFILIATION: Instituto de Ciencias Biológicas, Universidade Federal de Minas
Gerais, Avda Antonio Carlos, 6627, Bairro Pampulha, Belo Horizonte, CEP 31 270
901 Minas Gerais, Brazil.

REFERENCE: Vet Parasitol 2006 Apr 137(1-2):159-67

Blood transfusion is an important routine practice in veterinary 
medicine that generally involves the use of whole blood. Permanent blood
 donors must be vaccinated against viral infections that affect dogs and
 submitted periodically to clinical and serological examinations to 
detect blood-transmitted diseases. There is a very high risk of 
transmission of infectious agents, particularly protozoans due to their 
long incubation periods, subclinical persistence in infected animals and
 likelihood of remaining viable in bloodstocks. The aim of the present 
study was to identify the potential of asymptomatic and oligosymptomatic
 dogs for Leishmania infantum transmission as a result of transfusional 
practice. Nineteen Leishmania-seropositive adult dogs of both sexes and 
indeterminate breeds were selected as donors. The animals were 
classified as symptomatic, oligosymptomatic or asymptomatic after 
clinical examination and evaluated by ELISA, IFAT and bone marrow 
puncture biopsies. Whole blood and monocyte cells were collected and 
used for dog's serological evaluation and inoculation in culture medium 
as well as in hamsters. All but three dogs were positive for IFAT, ELISA
 and parasite demonstration in bone marrow aspirates, irrespective of 
their clinical conditions. Parasites were detected in 77% of the whole 
blood and 90% of the monocyte cultures. Six months after inoculation 
with whole blood or monocytes, hamsters developed infection and clinical
 symptoms of visceral leishmaniasis, as well as positive titres measured
 by ELISA. These results suggest that blood donors should be monitored 
periodically and rigorously for Leishmania infection, to prevent 
dissemination of the disease through blood transfusion.




PMID: 16517989
 

TITLE: Monoclonal gammopathy in human leishmaniasis.

AUTHORS: M L Randi, E Ruzzon, F Tezza, F Tezza, E Pacquola, F Fabris

AFFILIATION: Department of Medical and Surgical Sciences, Internal Medicine,
University of Padua Medical School, Padua, Italy. marialuigia.randi at unipd.it

REFERENCE: Neth J Med 2006 Feb 64(2):50-1

A 64-year-old female with IgGk monoclonal components (total 45 g/l) and 
30% abnormal plasma cells and plasmoblasts in bone marrow is reported. 
After the identification of leishmania in the bone marrow, liposomal 
amphotericin B was used and a progressive resolution of the gammopathy 
was documented.




PMID: 16501760
 

TITLE: Immunotherapy, immunochemotherapy and chemotherapy for American cutaneous
leishmaniasis treatment.

AUTHORS: Wilson Mayrink, Ana Cristina de Carvalho Botelho, Paulo Araújo
Magalhães, Sebastião Mariano Batista, Antonio de Oliveira Lima, Odair Genaro,
Carlos Alberto da Costa, Maria Norma de Melo, Marilene Susan Marques Michalick,
Paul Williams, Magno Dias, Waleska Teixeira Caiaffa, Evaldo do Nascimento,
George Luiz Lins Machado-Coelho

AFFILIATION: Departamento de Parasitologia, Instituto de Ciências Biológicas,
Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
wilsonmayrink at uol.com.br

REFERENCE: Rev Soc Bras Med Trop 2006 Jan-Feb 39(1):14-21

The first choice of treatment for American cutaneous leishmaniasis is 
the pentavalent antimonial drug. Although it has been shown that this 
treatment is mostly effective and indicated, some disadvantages should 
be taken into account such as side effects, long term treatment 
inconveniences and counter-indication for patients suffering from 
cardiopathy, nephropathy; yet, aging, pregnancy and other conditions. 
With the advent of the vaccine anti-American cutaneous leishmaniasis as 
a prophylactic measure, studies on therapy using the vaccine associated 
or not with other drugs have been performed by many investigators and it
 is currently among the alternative treatments and prevention measures 
for American cutaneous leishmaniasis. In conclusion, the association 
between antimony and vaccine (immunochemotherapy) showed the same cure 
rate when compared with the standard treatment (100%) and it was also 
able to reduce the salt volume in 17.9% and treatment length from 87 to 
62 days, decreasing side effects.




PMID: 16501761
 

TITLE: [Clinical findings of tegumentary leishmaniasis in children under five
years of age in an endemic area of Leishmania (Viannia) braziliensis]

AUTHORS: Julia Ampuero, Vanize Macêdo, Philip Marsden

AFFILIATION: Universidade de Brasília, Brasília, DF, Brazil.
ausangat at terra.com.pe

REFERENCE: Rev Soc Bras Med Trop 2006 Jan-Feb 39(1):22-6

A retrospective study was performed in a field clinic to characterize 
the clinical findings of tegumentary leishmaniasis in children from 0 to
 5 years old. The clinical records of 4,464 patients were analyzed at 
the Primary Health Center of Corte de Pedra, Presidente Tancredo Neves, 
Bahia, Brazil, from May 1987 to December 1995. Four hundred and ninety 
one (11.8%) children were identified among 4,275 new cases of 
tegumentary leishmaniasis registered at this Unit. The gender ratio (M:F
) for children under six years was 1.1:1. Cutaneous lesions predominated
 (98%), mainly skin ulcers (99%) located above the waist (p<0.05). 
Thirty five percent had multiple lesions. The observed magnitude of the 
disease in children, the similar proportion of cases in both genders and
 the location of the lesions suggest the possibility of peri or 
intradomiciliary transmission.




PMID: 16501764
 

TITLE: [Comparative study about the specific antileishmania of immunoglobulin G
and E as markers of infection and illness among dwellers of a visceral
leishmaniasis endemic area in São Luis, MA]

AUTHORS: Maria do Desterro Soares Brandão Nascimento, Geusa Felipa de Barros
Bezerra, Abderval Pinto Bandeira Neto, Leopoldo Muniz da Silva, José de
Macêdo Bezerra, Graça Maria de Castro Viana

AFFILIATION: Departamento de Patologia, Universidade Federal do Maranhão, São
Luís, MA. cnsd_ma at uol.com.br

REFERENCE: Rev Soc Bras Med Trop 2006 Jan-Feb 39(1):38-42

Comparative study regarding IgG and IgE anti-leishmania as markers of 
infection and illness among residents of a visceral leishmaniasis 
visceral leishmaniasis endemic area, São Luis, MA in the period from 
May 1999 to May 2000. All the 1,016 individuals younger than 16 years 
old were tested for the presence of IgG by ELISA. A total of 174 (17.1
%) children revealed a positive IgG test and 4 children showed symptoms 
of classical visceral leishmaniasis during the time of the survey: 85 
IgE anti-leishmania ELISA tests with positivity of 43.5% were realized. 
In this sample, all 7 children with past-visceral leishmaniasis in the 
sample were IgG positive and 4 (57.1%) were IgE positive, even after a 7
 year post treatment period. Three children with current visceral 
leishmaniasis were evaluated, and all of them were positive for both 
tests. The detection of antileishman IgE antibodies presented as a good 
marker for infection by Leishmania chagasi in endemic areas but not as a
 disease marker.








PMID: 16501765
 

TITLE: [Occurrence of American tegumentary leishmaniasis in the Mato Grosso do
Sul State associated to the infection for Leishmania (Leishmania) amazonensis]

AUTHORS: Maria Elizabeth Moraes Cavalheiros Dorval, Elisa Teruya Oshiro, Elisa
Cupollilo, Ana Cristina Camargo de Castro, Tulia Peixoto Alves

AFFILIATION: Departamento de Patologia, Centro de Ciências Biológicas e da
Saúde, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS.
bethparasito at nin.ufms.br

REFERENCE: Rev Soc Bras Med Trop 2006 Jan-Feb 39(1):43-6

Nine cases of American tegumentary leishmaniasis were reported at a 
Training Military Unit located in Bela Vista City, State of Mato Grosso 
do Sul. Parasites obtained from lesions of six patients were isolated in
 culture media followed by identification, through isoenzymes analysis, 
as being Leishmania amazonensis. This is the first evidence of the 
presence of the parasite in Mato Grosso do Sul.




PMID: 16501766
 

TITLE: [Antimicrobial susceptibility of aerobic bacteria isolated from
leishmaniotic ulcers in Corte de Pedra, BA]

AUTHORS: Luis Angel Vera, Jefferson Lessa Soares de Macedo, Isolina Allen
Ciuffo, Conceição Guerra Santos, João Barberino Santos

AFFILIATION: Universidade de Brasília, Brasília, DF.

REFERENCE: Rev Soc Bras Med Trop 2006 Jan-Feb 39(1):47-50

A prospective study regarding aspects of antimicrobial susceptibility 
aspects was realized among patients with tegumentary leishmaniasis in 
Corte de Pedra, Bahia. Cases were composed mainly of adolescent and 
adult farmer patients with single lesions. Staphylococcus aureus 
predominated (83%) in the cultures with susceptibility to the majority 
of antibiotics. A mixed bacterial flora in ulcers was encountered in 37
 (44.1%) patients. Among the gram-negative bacteria isolated, 
Enterobacter sp (13.1%), Proteus sp (8.3%), Pseudomonas aeruginosa (7.1
%) and Klebsiella sp (7.1%) were mainly found with susceptibility to 
ciprofloxacin, aminoglycosides, third generation cephalosporin and 
carbapenems.




PMID: 16501768
 

TITLE: [Study of the sand flies in American cutaneous leishmaniasis area, in the
municipality of Alto Caparaó and Caparaó, Minas Gerais State]

AUTHORS: Lara Saraiva, Juliana dos Santos Lopes, Gisele Brandão Machado
Oliveira, Francisco de Assis Batista, Alda Lima Falcão, José Dilermando
Andrade Filho

AFFILIATION: Colégio Técnico, Universidade Federal de Minas Gerais, Belo
Horizonte, MG, Brazil.

REFERENCE: Rev Soc Bras Med Trop 2006 Jan-Feb 39(1):56-63

In the period from November of 2000 to November of 2001, a study of sand
 flies was realized in the municipalities of Alto Caparaó and Caparaó 
with the objective of determining their seasonal variation, comparing 
the points of study related to the occurrence of these insects and 
detecting their ideal environments. Monthly collections were carried out
, with Falcão light traps at nine points, four traps per point, in the 
following environments: of animals shelter, forest (bush), coffee 
plantation and the external walls of houses. Lutzomyia intermedia (Lutz
 & Neiva, 1912) was the predominant species, and animal shelter the 
environment with the largest occurrence of sand flies. A significant 
difference in the composition of sand fly species was found in the 
studied points. Lutzomyia intermedia is the species suspected of 
transmitting Leishmania in the region.




PMID: 16269265
 

TITLE: TNF but not Fas ligand provides protective anti-L. major immunity in
C57BL/6 mice.

AUTHORS: Patricia Wilhelm, Florian Wiede, Anja Meissner, Norbert Donhauser,
Christian Bogdan, Heinrich Körner

AFFILIATION: Interdisziplinäres Zentrum für Klinische Forschung der
Universität Erlangen-Nürnberg, Nachwuchsgruppe 1, Nikolaus-Fiebiger-Zentrum,
Erlangen, Germany.

REFERENCE: Microbes Infect 2005 Dec 7(15):1461-8

The pro-inflammatory cytokine TNF is essential for a protective immune 
response to some but not all strains of Leishmania major. TNF-deficient 
mice of a resistant genetic background succumbed rapidly to an infection
 with L. major BNI. Another member of the TNF superfamily, Fas ligand (
FasL), has also been reported to be critical for the immune response to 
L. major. To test the relative importance of TNF versus FasL for the 
control of L. major BNI, we infected wildtype C57BL/6 (B6.WT), B6.TNF
(-/-), B6.gld and C57BL/6.gld x TNF(-/-) (B6.gld.TNF(-/-)) double-
negative mice. Visceral, fatal disease was only observed in B6.TNF(-/-) 
mice, but not in B6 gld mice. The course of infection and the immune 
response of B6.gld.TNF(-/-) mice were similar to those of B6.TNF(-/-) 
mice. B6.gld.TNF(-/-) mice had a high tissue parasite burden and 
expressed prominent amounts of inducible nitric oxide synthase (iNOS) in
 the skin, the lymph nodes (LN) and the spleen as previously reported 
for B6.TNF(-/-) mice, whereas the tissue parasite load and the iNOS 
expression of B6.gld mice resembled that of B6.WT controls. Neither the 
TNF- nor the FasL-deficiency exerted a detectable intrinsic effect on 
the proliferation of T cells. Thus, TNF, but not FasL is essential for 
the control of L. major BNI. The discrepancy between these and other 
published data are most likely due to the use of different strains of 
the pathogen.




PMID: 16511153
 

TITLE: Crystallization and preliminary X-ray analysis of Leishmania major
glyoxalase I.

AUTHORS: Antonio Ariza, Tim J Vickers, Neil Greig, Alan H Fairlamb, Charles S
Bond

AFFILIATION: Division of Biological Chemistry and Molecular Microbiology,
Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee
DD1 5EH, Scotland.

REFERENCE: Acta Crystallograph Sect F Struct Biol Cryst Commun 2005 Aug 61(Pt
8):769-72

Glyoxalase I (GLO1) is a putative drug target for trypanosomatids, which
 are pathogenic protozoa that include the causative agents of 
leishmaniasis. Significant sequence and functional differences between 
Leishmania major and human GLO1 suggest that it may make a suitable 
template for rational inhibitor design. L. major GLO1 was crystallized 
in two forms: the first is extremely disordered and does not diffract, 
while the second, an orthorhombic form, produces diffraction to 2.0 A. 
Molecular-replacement calculations indicate that there are three GLO1 
dimers in the asymmetric unit, which take up a helical arrangement with 
their molecular dyads arranged approximately perpendicular to the c axis
. Further analysis of these data are under way.








PMID: 16519257
 

TITLE: Management of visceral leishmaniasis: Indian perspective.

AUTHORS: S Agrawal, M Rai, S Sundar

AFFILIATION: Department of Medicine, Institute of Medical Sciences, Banaras
Hindu University, Varanasi-221 005, India. shyam_vns at satyarn.net.in

REFERENCE: J Postgrad Med 2005  51 Suppl 1():S53-7

Diagnosis and treatment of Indian visceral leishmaniasis (VL) is 
extremely unsatisfactory. For diagnosis, demonstration of parasites in 
splenic/marrow smears remains the gold standard, though k39 rapid strip 
test is a useful method in regions where access to parasite 
demonstration is difficult. pentavalent antimony remains the mainstay 
for the treatment of all forms of leishmaniasis globally; however, 
development of large-scale antimony resistance in Bihar has necessitated
 search for alternative drugs. Amphotericin B is the most effective, 
though toxic, drug for patients with refractory VL. Lipid formulations 
of amphotericin B, though safe and effective, are too expensive to be 
useful for poor patients of this region. These hold advantage as large 
quantity of the drug can safely be given over a short period of time, 
thus leading to a decrease in the hospital stay to a few days instead of
 several weeks. Oral miltefosine, an alkyl phospholipid, has recently 
been approved and marketed in India for the treatment of VL. Miltefosine
 cures 94% patients with VL if given in a daily dose of 50-100 mg for 28
 days. Most common adverse events are mild vomiting and diarrhea. 
Paromomycin, an amino glycoside, is undergoing a pivotal phase-III 
clinical trial, and is likely to be approved and available to patients 
with VL at an affordable cost. To protect the already scarce inventory 
of antileishmanial drugs, it is time that combination chemotherapy is 
introduced for the treatment of VL in India.




PMID: 16519258
 

TITLE: Post-marketing study to assess the safety, tolerability and effectiveness
of Fungisome: an Indian liposomal amphotericin B preparation.

AUTHORS: S S Sanath, N J Gogtay, N A Kshirsagar

AFFILIATION: Department of Clinical Pharmacology, Seth GS Medical College & KEM
Hospital, Parel, Mumbai 400 012, India.

REFERENCE: J Postgrad Med 2005  51 Suppl 1():S58-63

BACKGROUND: In May 2003, an indigenously developed liposomal 
amphotericin B (Fungisome) was introduced in the Indian market for the 
treatment of systemic fungal infections and visceral leishmaniasis. The 
present post marketing study assessed the safety and effectiveness of 
Fungisome in actual clinical practice. Setting and Design: Retrospective
 post marketing surveillance from four cities of India. METHODS: The 
present study was carried out for a period of 6 months (Jun-Nov 2004), a
 year after the introduction of the drug. A list of doctors who had 
prescribed and procured the drug was obtained from the distributor. 
Consent to participate and scrutinize the patients' source notes were 
obtained from the concerned doctors. All patients who had received 
Fungisome treatment were included. Data was collected from the patient's
 source notes on a predesigned proforma. They were then analyzed by 
descriptive statistics. Cost of Fungisome was calculated on the basis of
 dose used and number of days of treatment. RESULTS: Data were available
 for 109/144 patients from 35/40 physicians. Fungisome was administered 
at 1-3 mg/kg/day for 7-76 days. No serious adverse events related to the
 drug were observed in the study. Mild infusion-related adverse events 
were reported in 40 (36%), moderate in 11 (10%) of patients and severe 
in 2 (1.8%). None of the adverse events were certain to Fungisome 
exposure, 12 (11%) were probable, 28 (25 %) were possible, and 13 (11.9
%) were unlikely. Of the 91 assessable patients (received at least eight
 doses of Fungisome) for efficacy complete response was observed in 67 (
73.6%), 16 (17.5%) had partial responses, and 8 (8.7%) of patients had 
no response. The acquisition cost per day and per course treatment of 
different fungal infections ranged from (apprx) Rs 4500-8000 and 0.9-2.1
 lakh respectively. CONCLUSION: This postmarketing study documents the 
safety, tolerability, effectiveness and cost advantage of indigenously 
developed liposomal amphotericin B in the treatment of systemic fungal 
infections and febrile neutropenia in actual clinical practice.




PMID: 16522960
 

TITLE: Liposomal drug delivery system from laboratory to clinic.

AUTHORS: N A Kshirsagar, S K Pandya, B G Kirodian, S Sanath

AFFILIATION: Department of Clinical Pharmacology, Seth GS Medical College and
KEM Hospital, Parel, India. dcpkem at vsnl.com.

REFERENCE: J Postgrad Med 2005 Oct-Dec 51 Suppl():S5-S15

The main objective of drug delivery systems is to deliver a drug 
effectively, specifically to the site of action and to achieve greater 
efficacy and minimise the toxic effects compared to conventional drugs. 
Amongst various carrier systems, liposomes have generated a great 
interest because of their versatility. Liposomes are vesicular 
concentric bilayered structures, which are biocompatible, biodegradable 
and nonimmumnogenic. They can control the delivery of drugs by targeting
 the drug to the site of action or by site avoidance drug delivery or by
 prolonged circulation of drugs. Amphotericin B (Amp B) remains the drug
 of choice in most systemic mycoses and also as a second line treatment 
for Kala azar. However, its toxic effects often limit its use. Although 
the liposome delivery system has been tried for several drugs, only a 
few have been used in patients due to the slow development of necessary 
large-scale pharmaceutical procedures. This paper reviews the 
development of the technique for liposomal Amphotericin B (L-Amp-LRC-1, 
FungisomeTM) drug delivery system in our laboratory in collaboration 
with the department of Biochemistry, Delhi University in India and 
proving the safety and efficacy of this preparation in clinical practice
. It also attempts to compare the efficacy and benefits of our product 
for Indian patients with those of similar products and it includes facts
 from the publications that flowed from our work. As compared to 
conventional Amp B, Fungisome is infused over a much shorter period 
requiring a smaller volume and no premedication. It was found to be safe
 in patients who had developed serious unacceptable toxicity with 
conventional Amp B. In renal transplant patients, Fungisome did not 
produce any nephrotoxicity. Fungisome is effective in fungal infections 
resistant to fluconazole, conventional Amp B and in virgin and resistant
 cases of visceral leishmaniasis. The cost of any drug is of great 
significance, especially in India. We have therefore devoted a section 
of our review to the relative costs of our product and those of other 
commercially available products. This patient-worthy formulation is safe
, efficacious and cheaper than the commercially available formulation of
 liposomal amphotericin B. The product has been patented and technology 
transferred to a pharmaceutical company for marketing. Results of 
postmarketing study also document safety and efficacy as observed in 
premarketing studies. A brief review of this work is provided here.




PMID: 16522961
 

TITLE: Management of visceral leishmaniasis: Indian perspective.

AUTHORS: S Agrawal, M Rai, S Sundar

AFFILIATION: Department of Medicine, Institute of Medical Sciences, Banaras
Hindu University, Varanasi - 221 005, India. shyam_vns at satyam.net.in.

REFERENCE: J Postgrad Med 2005 Oct-Dec 51 Suppl():S53-7

Diagnosis and treatment of Indian visceral leishmaniasis (VL) is 
extremely unsatisfactory. For diagnosis, demonstration of parasites in 
splenic/marrow smears remains the gold standard, though k39 rapid strip 
test is a useful method in regions where access to parasite 
demonstration is difficult. pentavalent antimony remains the mainstay 
for the treatment of all forms of leishmaniasis globally; however, 
development of large-scale antimony resistance in Bihar has necessitated
 search for alternative drugs. Amphotericin B is the most effective, 
though toxic, drug for patients with refractory VL. Lipid formulations 
of amphotericin B, though safe and effective, are too expensive to be 
useful for poor patients of this region. These hold advantage as large 
quantity of the drug can safely be given over a short period of time, 
thus leading to a decrease in the hospital stay to a few days instead of
 several weeks. Oral miltefosine, an alkyl phospholipid, has recently 
been approved and marketed in India for the treatment of VL. Miltefosine
 cures 94% patients with VL if given in a daily dose of 50-100 mg for 28
 days. Most common adverse events are mild vomiting and diarrhea. 
Paromomycin, an amino glycoside, is undergoing a pivotal phase-III 
clinical trial and is likely to be approved and available to patients 
with VL at an affordable cost. To protect the already scarce inventory 
of antileishmanial drugs, it is time that combination chemotherapy is 
introduced for the treatment of VL in India.




PMID: 16522962
 

TITLE: Post-marketing study to assess the safety, tolerability and effectiveness
of FungisomeTM: An Indian Liposomal amphotericin B Preparation.

AUTHORS: S Hegde, N J Gogtay, N A Kshirsagar

AFFILIATION: Department of Clinical Pharmacology, Seth GS Medical College & KEM
Hospital, Parel, Mumbai - 400 012, India. dcpkem at vsnl.com.

REFERENCE: J Postgrad Med 2005 Oct-Dec 51 Suppl():S58-63

BACKGROUND: In May 2003, an indigenously developed liposomal 
amphotericin B (FungisomeTM) was introduced in the Indian market for the
 treatment of systemic fungal infections and visceral leishmaniasis. The
 present post marketing study assessed the safety and effectiveness of 
FungisomeTM in actual clinical practice. SETTING AND DESIGN: 
Retrospective post marketing surveillance from four cities of India. 
METHODS: The present study was carried out for a period of 6 months (Jun
-Nov 2004), a year after the introduction of the drug. A list of doctors
 who had prescribed and procured the drug was obtained from the 
distributor. Consent to participate and scrutinize the patients' source 
notes were obtained from the concerned doctors. All patients who had 
received FungisomeTM treatment were included. Data was collected from 
the patient's source notes on a predesigned proforma. They were then 
analyzed by descriptive statistics. Cost of FungisomeTM was calculated 
on the basis of dose used and number of days of treatment Results: Data 
were available for 109/144 patients from 35/40 physicians. FungisomeTM 
was administered at 1-3 mg/kg/day for 7-76 days. No serious adverse 
events related to the drug were observed in the study. Mild infusion-
related adverse events were reported in 40 (36%), moderate in 11 (10%) 
of patients and severe in 2 (1.8%). None of the adverse events were 
certain to FungisomeTM exposure, 12 (11 %) were probable, 28 (25 %) were
 possible and 13 (11.9%) were unlikely. Of the 91 assessable patients (
received at least eight doses of FungisomeTM) for efficacy complete 
response was observed in 67 (73.6%), 16 (17.5%) had partial responses 
and 8 (8.7%) of patients had no response. The acquisition cost per day 
and per course treatment of different fungal infections ranged from (
apprx) Rs 4500-8000 and 0.9 -2.1 lakh respectively. CONCLUSION: This 
postmarketing study documents the safety, tolerability, effectiveness 
and cost advantage of indigenously developed liposomal amphotericin B in
 the treatment of systemic fungal infections and febrile neutropenia in 
actual clinical practice.








PMID: 16519249
 

TITLE: Liposomal drug delivery system from laboratory to clinic.

AUTHORS: N A Kshirsagar, S K Pandya, G B Kirodian, S Sanath

AFFILIATION: Department of Clinical Pharmacology, Seth GS Medical College and
KEM Hospital, Parel, India. dcpkem at vsnl.com

REFERENCE: J Postgrad Med 2005  51 Suppl 1():S5-15

The main objective of drug delivery systems is to deliver a drug 
effectively, specifically to the site of action and to achieve greater 
efficacy and minimise the toxic effects compared to conventional drugs. 
Amongst various carrier systems, liposomes have generated a great 
interest because of their versatility. Liposomes are vesicular 
concentric bilayered structures, which are biocompatible, biodegradable 
and nonimmumnogenic. They can control the delivery of drugs by targeting
 the drug to the site of action or by site avoidance drug delivery or by
 prolonged circulation of drugs. Amphotericin B (Amp B) remains the drug
 of choice in most systemic mycoses and also as a second line treatment 
for Kala azar. However, its toxic effects often limit its use. Although 
the liposome delivery system has been tried for several drugs, only a 
few have been used in patients due to the slow development of necessary 
large-scale pharmaceutical procedures. This paper reviews the 
development of the technique for liposomal Amphotericin B (L-Amp-LRC-1, 
Fungisome) drug delivery system in our laboratory in collaboration with 
the department of Biochemistry, Delhi University in India and proving 
the safety and efficacy of this preparation in clinical practice. It 
also attempts to compare the efficacy and benefits of our product for 
Indian patients with those of similar products and it includes facts 
from the publications that flowed from our work. As compared to 
conventional Amp B, Fungisome is infused over a much shorter period 
requiring a smaller volume and no premedication. It was found to be safe
 in patients who had developed serious unacceptable toxicity with 
conventional Amp B. In renal transplant patients, Fungisome did not 
produce any nephrotoxicity. Fungisome is effective in fungal infections 
resistant to fluconazole, conventional Amp B and in virgin and resistant
 cases of visceral leishmaniasis. The cost of any drug is of great 
significance, especially in India. We have therefore devoted a section 
of our review to the relative costs of our product and those of other 
commercially available products. This patient-worthy formulation is safe
, efficacious and cheaper than the commercially available formulation of
 liposomal amphotericin B. The product has been patented and technology 
transferred to a pharmaceutical company for marketing. Results of 
postmarketing study also document safety and efficacy as observed in 
premarketing studies. A brief review of this work is provided here.




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

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

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


PMID: 12089677
 

TITLE: Radical cure of experimental cutaneous leishmaniasis by the
bisphosphonate pamidronate.

AUTHORS: Noris Rodriguez, Brian N Bailey, Michael B Martin, Eric Oldfield, Julio
A Urbina, Roberto Docampo

AFFILIATION: Laboratory of Molecular Parasitology, Department of Pathobiology,
College of Veterinary Medicine, University of Illinois at Urbana-Champaign,
Urbana, Illinois 61802, USA.

REFERENCE: J Infect Dis 2002 Jul 186(1):138-40

The effects in vivo of the bisphosphonate drug pamidronate, used in bone
 resorption therapy, were investigated in an experimental model of 
cutaneous leishmaniasis. Pamidronate at an intraperitoneal dose of 10 mg
/kg/day for 5 days effects a radical cure of cutaneous leishmaniasis in 
Balb/c mice, as evidenced by long-term disappearance of lesions; 
disappearance of amastigotes in lesion sites, as determined by 
histopathological analysis and cultivation of material obtained from 
lesions; and polymerase chain reaction analysis of necropsy material, 
using probes specific for kinetoplast DNA. Pamidronate is, therefore, a 
new lead compound for the synthesis of drugs effective against cutaneous
 leishmaniasis.




REQUEST: [ leishmania ]

(12 articles match this request. 9 articles matching other requests removed)



PMID: 16487540
 

TITLE: The Structure of the Transition State of the Heterodimeric Topoisomerase
I of Leishmania donovani as a Vanadate Complex with Nicked DNA.

AUTHORS: Douglas R Davies, Adeel Mushtaq, Heidrun Interthal, James J Champoux,
Wim G J Hol

AFFILIATION: Department of Biochemistry, Box 357742, University of Washington,
Seattle, WA 98195-7742, USA.

REFERENCE: J Mol Biol 2006 Apr 357(4):1202-10

Type IB topoisomerases are essential enzymes that are responsible for 
relaxing superhelical tension in DNA by forming a transient covalent 
nick in one strand of the DNA duplex. Topoisomerase I is a target for 
anti-cancer drugs such as camptothecin, and these drugs also target the 
topoisomerases I in pathogenic trypanosomes including Leishmania species
 and Trypanosoma brucei. Most eukaryotic enzymes, including human 
topoisomerase I, are monomeric. However, for Leishmania donovani, the 
DNA-binding activity and the majority of residues involved in catalysis 
are located in a large subunit, designated TOP1L, whereas the catalytic 
tyrosine residue responsible for covalent attachment to DNA is located 
in a smaller subunit, called TOP1S. Here, we present the 2.27A crystal 
structure of an active truncated L.donovani TOP1L/TOP1S heterodimer 
bound to nicked double-stranded DNA captured as a vanadate complex. The 
vanadate forms covalent linkages between the catalytic tyrosine residue 
of the small subunit and the nicked ends of the scissile DNA strand, 
mimicking the previously unseen transition state of the topoisomerase I 
catalytic cycle. This structure fills a critical gap in the existing 
ensemble of topoisomerase I structures and provides crucial insights 
into the catalytic mechanism.




PMID: 16499336
 

TITLE: A pyrimidine-beta-carboline and other alkaloids from Annona foetida with
antileishmanial activity.

AUTHORS: Emmanoel V Costa, Maria Lúcia B Pinheiro, Clahildek M Xavier,
Jefferson R A Silva, Ana Cláudia F Amaral, Afonso D L Souza, Andersson
Barison, Francinete R Campos, Antonio G Ferreira, Gérzia M C Machado, Leonor L
P Leon

AFFILIATION: Departamento de Química, Universidade Federal do Amazonas, Avenida
Gen. Rodrigo Otavio Jordão Ramos, 3000, Coroado, CEP 69077-000 Manaus,
Amazonas, Brazil.

REFERENCE: J Nat Prod 2006 Feb 69(2):292-4

Bioassay-guided fractionation of the bark extract of Annona foetida 
afforded a new antileishmanial pyrimidine-beta-carboline alkaloid, N-
hydroxyannomontine (1), together with the previously reported 
annomontine (2), O-methylmoschatoline (3), and liriodenine (4). The 
structure of compound 1 was established on the basis of extensive 1D and
 2D NMR and MS analyses. This is the third reported pyrimidine-beta-
carboline-type alkaloid and is particularly important for Annona genus 
chemotaxonomy. In addition, all compounds exhibit in vitro 
antileishmanial activity against promastigote forms of Leishmania 
braziliensis. Compounds 2 and 4 showed better activity than compounds 1 
and 3 against L. braziliensis. Compound 2 was not active against L. 
guyanensis.




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

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

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


PMID: 3037057
 

TITLE: In vitro antileishmanial activity of inhibitors of steroid biosynthesis
and combinations of antileishmanial agents.

AUTHORS: J D Berman, J V Gallalee

REFERENCE: J Parasitol 1987 Jun 73(3):671-3




REQUEST: [ sand fly ]

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



REQUEST: [ sandfly ]

(1 article matches this request)



PMID: 16256057
 

TITLE: Acute meningitis owing to phlebotomus fever Toscana virus imported to
France.

AUTHORS: Gilles Defuentes, Christophe Rapp, Patrick Imbert, Jean-Paul Durand,
Thierry Debord

AFFILIATION: Service des Maladies Infectieuses et Tropicales, Hôpital Bégin,
Saint Mandé, France.

REFERENCE: J Travel Med 2005 Sep-Oct 12(5):295-6

Acute lymphocytic meningitis, seen in France in summer, is often due to 
enteroviruses. Arboviruses as West Nile and tick-borne encephalitis do 
exist in Europe, but other viruses are rarely considered in patients 
unless they have had recent tropical travel. Toscana virus infection, 
which is endemic, especially in Italy,1-3 has been documented in some 
European travelers returning from Italy,4-6 but surprisingly was not 
documented in France until recently.7 We report a case of meningitis 
caused by Toscana virus imported to France.















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