LEISHMANIASIS: NUEVOS TRATAMIENTOS, MECANISMOS DE ACCIÓN Y SUS IMPLICACIONES
Resumen
Resumen
Los tratamientos para el control de la Leishmaniasis se fundamentan casi exclusivamente en antimoniales pentavalentes, compuestos de alta toxicidad para el organismo. Este tipo de medicación tiene una buena efectividad en pacientes inmunocompetentes, pero en personas inmunosuprimidas de zonas endémicas la eficacia se ha visto disminuida y se han presentado cada vez más casos de resistencia al tratamiento, razón que ha obligado a la industria farmacéutica a desarrollar nuevos medicamentos que conserven la efectividad, disminuyan la toxicidad y en lo posible ejerzan un papel estimulante en el desarrollo de la respuesta inmune del individuo hacia el parásito para que puedan ser utilizados con éxito en pacientes con alteraciones del sistema inmune. La presente revisión tiene como objeto desarrollar una breve descripción de estos nuevos tratamientos, sus mecanismos de acción y las implicaciones que tienen en las personas que son tratados con ellos.
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BIBLIOGRAFÍA
Adler, S., and M. Ber. (1941). The transmission of
Leishmania tropica by the bite of Phlebotomus papatasii.
Indian J. Med. Res. Vol 29:803–809.
Ambroise-Thomas, P. (2001). Parasitic diseases
a n d i m m u n o d e fi c i e n c i e s . P a r a s i t o l o g y . Vo l
(Suppl.):s65–s71.
Ahuja, S. S., R. L. Reddick, N. Sato, E. Montalbo,
V. Kostecki, W. Zhao, M. J. Dolan, P. C. Melby, and S. K.
Ahuja., (1999). Dendritic cell (DC)-based anti-infective
strategies: DCs engineered to secrete IL-12 are a potent
vaccine in a murine model of an intracellular infection. J.
Immunol. 163: 3890–3897.
Berman, J. (2001). Leishmaniasis. Current
Treatment Options in Infectious Diseases. Vol 3: 333-336.
Berman, J. D. 1997. Human leishmaniasis: clinical,
diagnostic, and chemotherapeutic developments in the last
years. Clin. Infect. Dis. Vol 24:684–703.
Beckers T., Voegeli R., Hilgard P., (1994).
M o l e c u l a r a n d c e l l u l a r e f f e c t s o f
hexadecylphosphocholine (Miltefosine) in human myeloid
leukaemic cell lines. Eur. J. Cancer. 30A:2143-50.
Blitterswijk V.W.J, Hilkmann H, Storme GA.,
(1987). Accumulation of an alkyl lysophospholipid in
tumor cell membranes affects membrane fluidity and tumor
cell invasion. Lipids;22:820–3.
Bibby D. C., Davies N. M., Tucker I. G. (2000).
Mechanisms by which cyclodextrins modify drug release
from polymeric drug delivery systems. International
Journal of Pharmaceutics. Vol 197: 1–11
Bryceson, A. 2001. A policy for leishmaniasis with
respect to the prevention and control of drug resistance.
Trop Med Int Health. Vol 6: 928-934.
Croft S.L. (2001). Monitoring drug resistance in
leishmaniasis. Tropical Medicine and International Health.
Vol 6 (11): 899-905.
Davidson, R. N., Martino L., Gradoni L., Giacchino
R., Gaeta G.B., Pempinello R., Scotti S., Cascio A.,
Castagnola E., Maisto A., Gramiccia M., Caprio D.,
Wilkinson R.J. and Bryceson A.D. (1996). Short-course
treatment of visceral leishmaniasis with liposomal
amphotericin B (AmBisome). Clin. Infect. Dis. Vol 22:
–943.
Demicheli C., Ochoa R., Da Silva J.B.B., Falcäo C.,
Rossi B., De Melo A.L., Sinisterra R.D., and Frézard F.
(2004). Oral delivery of Meglumine Antimoniate-β-
Cyclodextrin complex for treatment of Leishmanisis.
Antimicrobial agents and Chemotheraphy. J. Vol 48 (1):
-103.
Dzamitika S.A., Falcao C.A.B., Oliveira F.B.,
Marbeuf C., Garnier-Suillerot A., Demicheli C., Rossi-
Bergmannb B., Frezard F. (2006). Role of residual Sb(III)
in meglumine antimoniate cytotoxicity and MRP1-
mediated resistance. Chemico-Biological Interactions Vol.
: 217–224
E i b l , H . , U n g e r , C . ( 1 9 9 0 ) .
Hexadecylphosphocholine: a new and selective antitumor
drug. Cancer Treat. Rev. Vol 17: 233-242.
Escobar, P., Matu, S., Marques, C., Croft, S.L.,
0 0 2 . S e n s i t i v i t i e s o f L e i s h m a n i a s p e c i e s t o
hexadecylphosphocholine (miltefosine), ET-18- OCH(3)
(edelfosine) and amphotericin B. Acta Trop. Vol 81: 151-
Guerin, P. J., Olliaro P., Sundar S., Boelaert M.,
Croft S. L., Desjeux P., Wasunna M. K. and Bryceson A.
(2002). Visceral Leishmanisis: Current Status of Control,
Diagnosis, and Treatment, and a proposed research and
development agenda. The Lancet Infectious Diseases. Vol
: 494-500.
Hedges, A. R. (1998). Industrial applications of
cyclodextrins. Chemistry Review. Vol 98: 2035-2042.
Hilgard, P., Klener T., Stekar J., and Unger C.
(1993). Alkylphosphocholines: a new class of membrane
active anticancer agents. Cancer Chemoter. Pahrmacol.
:90-95.
Hochhuth C. H., Vehmeyer K., Eibl H., Unger C.
(1992). Hexadecyolphosphocholine induces interferongamma
secretion and expresión of GM-CSF mRNA in
human mononuclear cells. Cell Immunol. 141:161-8.
Hockhertz, S., G. Franke, I. Paulini, and M.-L.
Lohmann-Matthes. (1991). Immunotherapy of murine
visceral leishmaniasis with murine recombinant interferong
and MTP-PE encapsulated in liposomes. J. Interferon
Res. Vol 11(3):177-185.
Irie T., Uekama K. (1997). Pharmaceutical
Applications of Cyclodextrins. III. Toxicological Issues and Safety Evaluation. Journal of Farmaceutical Sciences.
Vol 86: 147-162.
Kapoor, P., Sachdev M. and Madhibala R. (2000).
Inhibition of glutathione synthesis as a hemotherapeutic
strategy for leishmaniasis. Trop. Med. Int. Health. Vol 6:
–442.
Langer R. (1990). New Methods of drug delivery.
Science, Vol 249: Pág. 1527-1532.
Lasic, D. D. (1998). Novel application of
liposomes. Trends in Biotechnology. Vol 16: 307-312.
Li J., Xiao H., Li J., Zhong Y. (2004). Drug carrier
systems based on water-soluble cationic B-ciclodextrine
polymers. International Journal of Pharmaceutics. Vol 278:
–342
Loftsson T. And Masson M. (2001). Cyclodextrins
in topical drug formulations: theory and practice.
International Journal of Pharmaceutics. Vol 225: 15-30.
L o f t s s o n T. a n d B r e w s t e r M . E . ( 1 9 9 6 ) .
Pharmaceutical applications of cyclodextrins. Drug
solubilization and stabilization. Pharmaceutical Sciences,
Vol 85 (10): 1017-1025.
Lucumi, A., Robledo, S., Gama V., Saravia N.
(1998). Sensitivy of Leishmania viannia panamensis Is
Correlated with the Formation of Cleaveble DNA-Protein
Complexes. Antimicrobial Agents and Chemotherapy. Vol
(8): 1990-1995.
Maldonado R. A, Pérez O.O.G, Ochoa B.R. (2007).
Formulación y evaluación in vivo de un compuesto
leishmanicida (Hexadecilfosfocolina), en sistemas de
l i b e r a c i ó n c o n t r o l a d a t i p o c i c l o d e x t r i n a . R e v i s t a
Biomédica, Vol 27 (s2): 164.
Manunza, B., Deiana S., Pintore M., Gessa C.
(1997). Structure and internal motion of solvated betacyclodextrine:
a molecular dynamics study. Journal of
Molecular Structure (Theochem). Vol 419: 133-137.
Martins P. S., Ochoa R., Pimenta A. M. C., Ferreira
L. A. M., Meloe A. L., da Silva J. B. B., Sinisterra R. D.,
Demicheli C., Frezard F. (2006). Mode of action of Bcyclodextrin
as an absorption enhancer of the water-soluble
drug meglumine antimoniate. International Journal of
Pharmaceutics. Vol 325: 39–47.
Menez C., Buyse M., Chacun H., Farinotti R.,
Barratt. G. (2006). Modulation of intestinal barrier
properties by miltefosine. Biochemical pharmacology Vol
: 486–496.
Mittal, N., Gupta N., Saksena S., Goyal N., Roy U.
and Rastogi A. K. (1998). Protective effect of Picroliv from
Picorhiza kurroa against Leishmania donovani infections
in Mesocricetus auratus. Life Sci. Vol 63: 1823–1834.
Murphy, M. L., S. Cotterell, M. Gorak, C. R.
Engwerda, and P. M. Kaye., (1998). lockade of CTLA-4
enhances host resistance to the intracellular pathogen,
Leishmania donovani. J. Immunol. Vol 161:4153–4160.
Murray, H. W., Oca, M.J., Granger, A. M. and
S c h r e i b e r R . D . ( 1 9 8 9 ) . S u c c e s s f u l r e s p o n s e t o
chemotherapy in experimental visceral leishmaniasis:
requirement for T cells and effect of lymphokines. J. Clin.
Investig. Vol 83: 1254–1259.
Murray, H. W. (1990). Effect of continuous
administration of interferongamma in experimental
visceral leishmaniasis. J. Infect. Dis. Vol 161:992–994.
Murray, H. W., J. Hariprashad, and R. Fichtl. (1993
a.). Treatment of experimental visceral leishmaniasis in a Tcell-
deficient host: response to amphotericin B and
pentamidine. Antimicrob. Agents Chemother. Vol
:1504–1505
Murray, H. W., Miralles G. D., Stoeckle M. Y. and
McDermott D. F. (1993 b.). Role and effect of Interleukin-2
in experimental visceral leishmaniasis. J. Immunol. Vol
: 929–934.
Murray, H. W., and J. Hariprashad. (1995).
Interleukin 12 is effective treatment for an established
systemic intracellular infection: experimental visceral
leishmaniasis. J. Exp. Med. Vol 181:387–391.
M u r r a y, H . W. , J u n g b l u t h A . , R i t t e r E . ,
Montelibano C. and Marino M.W. (2000). Visceral
leishmaniasis in mice devoid of tumor necrosis factor and
response to treatment. Infect. Immun. Vol 68: 6289–6293.
Murray H.W. (2001). Minireview, Clinical and
E x p e r i m e n t a l A d v a n c e r i n Tr e a t m e n t o f Vi s c e r a l Leishmaniasis. Antimicrobial Agents and Chemotherapy.
Vol 45 (8): 2185-2197.
Ochoa, R. (2003). Síntese e formulacao de
compostos de antimonio ativos contra a Leishmanioses em
sistemas de liberacao do tipo: ciclodextrinas, polímeros
biodegradáveis e lipossomas. Universidade Federal de
Minas Gerais, Belo Horizonte.
Ohkusu, K., Yoshimoto T., Takeda K., Ogura T.,
Kashiwamura S.-I., Iwakura Y., Akira S., Okamura H. and
Nakanishi K. (2000). Potentiality of interleukin 18 as a
useful reagent for treatment and prevention of Leishmania
major infection. Infect. Immun. Vol:68, Pág. 2449–2456.
Papagiannaros A., Bories C., Demetzos C., Loiseau
P.M. (2005). Antileishmanial and trypanocidal activities of
new miltefosine liposomal formulations. Biomedicine &
Pharmacotherapy Vol 59: 545–550
Pérez-Victoria J.M., Pérez-Victoria F.J., Castanys S. y
Gamarro F. (2006). Estrategias terapéuticas y bases
moleculares de la resistencia a fármacos frente a la
leishmaniasis. Instituto de Parasitología y Biomedicina
"López-Neyra" (CSIC) Parque Tecnológico de Ciencias de
la Salud Avda. del Conocimiento, s/n. 18100 Armilla,
GRANADA (SPAIN). josepv@ipb.csic.es
Perez-Victoria J.M., Perez-Victoria F.J., Parodi-
Talice I.A, Jimenez A.G., Ravelo S.C. and Gamarro F.
(2001). Alkyl-lysophospholipid resistance in multidrugresistant
Leishmania tropica and chemosensitization by a
n o v e l P g l y c o p r o t e i n - l i k e t r a n s p o r t e r m o d u l a t o r.
Antimicrob Agents Chemother Vol 45: 2468-2474.
Pintado V., Lopez-Velez R. (2001). HIV –
associated visceral leishmaniasis. Clinical Microbiology
Infection. Vol 7: 291-300.
R a j e w s k i R . A . a n d S t e l l a V. J . ( 1 9 9 6 ) .
Pharmaceutical Applications of Cyclodextrins. 2. In vivo
Delivery. Journal of Pharmaceutical Sciences, Vol 85 (11):
-1169.
Singh M., Sharma R. y Banerjee U. C. (2002).
B i o t e c h n o l o g i c a l a p p l i c a t i o n s o f c y c l o d e x t r i n s .
Biotechnology Advances. Vol 20: 341-359.
Singh S. (2006). New developments in diagnosis
of leishmaniasis. Indian J. Med. Res. Vol 123: 311-330.
Soto J., Berman J. (2006). Treatment of New
Wo r l d c u t a n e o u s l e i s h m a n i a s i s w i t h m i l t e f o s i n e , Transactions of the Royal Society of Tropical Medicine and
Hygiene. Vol 100S: S34—S40
Soto J., Toledo J.T. (2007). Oral miltefosine to treat
new world cutaneous leishmaniasis. The Lancet Infectious
Diseases, Vol 7: 7.
Sundar S., Sinha P.R., Agrawal N. K. (1998). A
cluster of cases of severe cardiotoxicity among kala-azar
patients treated with a high-osmolarity lot of sodium
antimony gluconate. American Tropical Medicine and
Hygiene. Vol 59: 193-203.
Sundar S. (2001). Drug resistance in Indian
visceral leishmaniasis. Trop. Med. Int. Health. Vol 6: 849-
Sypek, J. P., C. L. Chung, S. E. H. Mayor, J. M.
Subramanyam, S. J. Goldman, D. D. Sieburth, S. F. Wolf, &
S c h a u b R . G . . ( 1 9 9 3 ) . R e s o l u t i o n o f c u t a n e o u s
leishmaniasis: interleukin 12 initiates a protective T helper
type 1 immune respoonse. J. Exp. Med. Vol 177: 1797–1802.
Thakur, C. P., Kanyok T. P., Pandey A. K., Sinha G.
P., Messick C. and Olliaro P. (2000). Treatment of visceral
l e i s h m a n i a s i s w i t h i n j e c t a b l e p a r a m y o m y c i n (aminosidine). An open-label randomized phase-II clinical
study. Trans. R. Soc. Trop. Med. Hyg. Vol 94: 432–433.
Thakur, C. P., R. K. Singh, S. M. Hassan, R. Kumar,
S. Narain, and Kumar, A. (1999). Amphotericin B
deoxycholate treatment of visceral leishmaniasis with
newer modes of administration and precautions: a study of
cases. Trans. R. Soc. Trop. Med. Hyg. Vol 93: 319–323.
Vázquez T.J. (2000). Ciclodextrinas. Universidad
de Santiago. Departamento de Química Física, Facultad de
Ciencias, Lugo, España. 1-19.
Vásquez L., Scorza J., Dagert V., Scorza J.V.,
Vicuna-Fernandez N., Petit de Peña Y., López S., Bendeza
H-, Rojas E., Vásquez L., and Pérez B. (2006).
Pharmacokinetics of Experimental Pentavalent Antimony
After Intramuscular Administration in Adult Volunteers.
Current Therapeutic Research. Vol. 67 (3): 193-203.
Villiers, A. (1981). Chimie Organic – sur la
transformation de la fécule en dextrine per le ferment
butyrique. Compt. Render. Vol 112: 536-540
Wieder T, Orfanos CE, Geilen CC., (1998).
Induction of ceramide-mediated apoptosis by the
anticancer phospholipid analog hexadecylphosphocholine.
J Biol Chem;273:11025–31.
Zeisig R., Rudolf M., Eue I., Arndt D. (1995).
Influence of hexadecylphosphocholine on the release of
tumor necrosis factor and nitroxide from peritoneal
macrophages in vitro. J. Cancer Res. Clin. Oncol. 121: 69-
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