RESUMEN
The need of intracellular parasites to retrieve nutrients and fulfill their energy requirements is achieved by manipulating the host's metabolism. With the spread of AIDS, research on purine metabolism has gained in importance with the aim to develop drugs against opportunistic infections. Many studies over the past ten years have yielded contradictory results, but this review tries to clarify these findings by exposing the latest data concerning purine transport and the specific activities of the major enzymes of the purine salvage pathway of Toxoplasma gondii, Plasmodium falciparum and Cryptosporidium parvum.
Asunto(s)
Cryptosporidium parvum/metabolismo , Necesidades Nutricionales , Plasmodium falciparum/metabolismo , Purinas/metabolismo , Toxoplasma/metabolismo , Animales , Antiprotozoarios , Cryptosporidium parvum/enzimología , Cryptosporidium parvum/genética , Interacciones Huésped-Parásitos , Plasmodium falciparum/enzimología , Plasmodium falciparum/genética , Especificidad de la Especie , Especificidad por Sustrato , Toxoplasma/enzimología , Toxoplasma/genéticaRESUMEN
OBJECTIVE: The main of this study was to show the rapidity of the protoscolicide action of a synthetic compound, dipeptide methyl ester when it is injected under echographic control into hydatid cyst of sheep. MATERIALS AND METHODS: Fourthty sheep with hydatid cysts, repaired at echography and punctionable are treated by dipeptide methyl ester injection at the dose of 110 mM. RESULTS: In vitro tests have allowed to define the efficacy dose of dipeptide methyl ester which is 110 mM. At echography, after injection of the drug, from the first minutes, a detachment of the inner membrane, a diminution of the size of the treated cyst were observed. The cyst content is modified. The sheep autopsy was realized after 4.6.12 and 17 weeks after the injection and showed a size reduction, a treated cyst calcification. CONCLUSION: The dipeptide methyl ester injection into hydatid cyst induces rapidly a morphological alteration, they are calcified. The advantage of this compound is its very rapidity action, this could decrease dissemination risks of hydatid liquid in the organism during operation. Also, this drug permits to reduce the operation time.
Asunto(s)
Dipéptidos/farmacología , Equinococosis/tratamiento farmacológico , Animales , Equinococosis/diagnóstico por imagen , Inyecciones , Ovinos , Ultrasonografía IntervencionalRESUMEN
Purine nucleoside phosphorylase (PNP, EC 2.4.2.1) activity was revealed by enzyme histochemistry in Toxoplasma gondii ME49 strain isolated from murine cerebral cysts and from in vitro cultivation. The activity of the enzyme was revealed by an insoluble electron-opaque precipitate of lead phosphate at the site of the reaction. In bradyzoites and tachyzoites of T. gondii, the enzyme activity could be observed only in the cytoplasm. In bradyzoites, one or two foci of important PNP activity were detected near the nucleus. In tachyzoites, an important PNP activity underlined the plasma membrane. For both bradyzoites and tachyzoites, localization neither in the nucleus nor in cytoplasmic organelles could be detected.
Asunto(s)
Purina-Nucleósido Fosforilasa/metabolismo , Purina-Nucleósido Fosforilasa/ultraestructura , Toxoplasma/enzimología , Animales , Transporte Biológico , Encéfalo/ultraestructura , Línea Celular Tumoral , Membrana Celular/ultraestructura , Núcleo Celular/ultraestructura , Quistes/ultraestructura , Citoplasma/ultraestructura , Ratones , Microscopía Electrónica , Purina-Nucleósido Fosforilasa/análisisRESUMEN
In a previous work, we have showed in mice infected with an avirulent strain of Toxoplasma gondii and receiving a didanosine treatment, an important decrease of brain cysts. It is why, the purpose of this study was to investigate the effect of didanosine treatment on AIDS patients having developed Toxoplasma encephalitis. 60 patient reports were analyzed: 22 patients (group 1) did not received didanosine in their antiretroviral treatment and 38 (group 2) were treated with didanosine. The results showed that an antiretroviral therapy was prescribed for 93% of patients, 50% of them received only zidovudine and protease inhibitors were prescribed for 37%. The regimens given most frequently were those including zidovudine plus lamivudine or zidovudine plus indinavir. Among the group 1, 18% have had a relapse of Toxoplasma encephalitis. In the group 2, 37% of the patients suffered from one episode of TE while 16% have had two TE after the pause in their didanosine treatment, the maximum occurring between 4 and 24 months after the pause of didanosine. This study showed that didanosine seems to have an effect on cerebral cysts. Also, this work made a synthesis about the different treatment used in AIDS patients and the new molecules yet in development against T. gondii.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Didanosina/uso terapéutico , Encefalitis/epidemiología , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Toxoplasmosis Cerebral/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/parasitología , Adulto , Anciano , Estudios de Cohortes , Quimioterapia Combinada , Encefalitis/tratamiento farmacológico , Encefalitis/parasitología , Femenino , Francia/epidemiología , Infecciones por VIH/complicaciones , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Toxoplasmosis Cerebral/tratamiento farmacológico , Toxoplasmosis Cerebral/parasitologíaRESUMEN
Benzimidazole-4,7-diones derivatives substituted at 1- and/or 2-position have been synthetized and tested as inhibitors of purine nucleoside phosphorylase (PNP), isolated from two strains of Toxoplasma gondii (RH and ME 49). They were identified as inhibitors of both enzymes.