[Leish-l] Fwd: Articles found by RefScout 2006/03/15 2006/11
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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 ClÃnica 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 BrasÃlia, BrasÃlia, 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
LuÃs, 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 BrasÃlia, BrasÃlia, 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 QuÃmica, 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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