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Gamme d'année
1.
Salvador; s.n; 2013. 86 p. ilus.
Thèse Dans Portugais | LILACS | ID: biblio-1000887

Résumé

O prognóstico da leishmaniose cutânea (LC) com o uso dos antimoniais pentavalentes (Sb+5) de um modo geral é considerado bom, embora alguns casos tornem-se refratários à terapêutica tradicional. Infelizmente, não existem marcadores de gravidade da doença ou marcadores de resposta terapêutica, limitando a utilização de formas de tratamento mais efetivas. Em alguns casos, porém, existe a necessidade de utilizar outras drogas, como a anfotericina B (desoxocolato) e as pentamidinas (isotionato e mesilato), consideradas como drogas de 2ª escolha no tratamento das leishmanioses, sendo de fundamental importância à busca de novos esquemas terapêuticos. O objetivo do estudo foi comparar a eficácia entre o antimoniato-N-metilglucamina (Glucantime®) e o isotionato de pentamidina (Pentacarinat®) no tratamento da forma cutânea da leishmaniose tegumentar (LT)...


The prognosis of cutaneous leishmaniasis (CL) with the use of pentavalents antimonials (Sb+5) is generally considered good, although in some cases have become refractory to conventional therapy. Unfortunately there are no markers of disease severity or markers of therapeutic response, limiting the use of more effective forms of treatment. In some cases, however, there is a need for other drugs such as amphotericin B (desoxycholate) and pentamidine (isethionate and mesylate), which are considered as the second choice in the treatment of leishmaniasis, since few studies with reduced doses of these drugs demonstrated encouraging results in tegumentary leishmaniasis (TL), which is paramount in the search for new therapeutic regimens using proven antileishmanial drugs. We have compared the effectiveness between the N-methylglucamine antimoniate (Glucantime®) and pentamidine isethionate (Pentacarinat®) in the treatment of CL in an endemic area of tegumentary leishmaniasis (TL)...


Sujets)
Animaux , Leishmania/immunologie , Leishmania/parasitologie , Leishmania/pathogénicité , Peau/traumatismes , Pentamidine/analyse , Pentamidine/pharmacologie , Pentamidine/immunologie
2.
Mem. Inst. Oswaldo Cruz ; 106(8): 1032-1038, Dec. 2011. graf, tab
Article Dans Anglais | LILACS | ID: lil-610982

Résumé

The need for drug combinations to treat visceral leishmaniasis (VL) arose because of resistance to antimonials, the toxicity of current treatments and the length of the course of therapy. Calcium channel blockers (CCBs) have shown anti-leishmanial activity; therefore their use in combination with standard drugs could provide new alternatives for the treatment of VL. In this work, in vitro isobolograms of Leishmania (Leishmania) chagasi using promastigotes or intracellular amastigotes were utilised to identify the interactions between five CCBs and the standard drugs pentamidine, amphotericin B and glucantime. The drug interactions were assessed with a fixed ratio isobologram method and the fractional inhibitory concentrations (FICs), sum of FICs (ΣFICs) and the overall mean ΣFIC were calculated for each combination. Graphical isobologram analysis showed that the combination of nimodipine and glucantime was the most promising in amastigotes with an overall mean ΣFIC value of 0.79. Interactions between CCBs and the anti-leishmanial drugs were classified as indifferent according to the overall mean ΣFIC and the isobologram graphic analysis.


Sujets)
Animaux , Cricetinae , Souris , Amphotéricine B/pharmacologie , Antiprotozoaires/pharmacologie , Inhibiteurs des canaux calciques/pharmacologie , Leishmania/effets des médicaments et des substances chimiques , Leishmaniose viscérale/traitement médicamenteux , Macrophages péritonéaux/effets des médicaments et des substances chimiques , Pentamidine/pharmacologie , Association de médicaments/méthodes , Leishmaniose viscérale/parasitologie , Mesocricetus , Souris de lignée BALB C , Tests de sensibilité parasitaire
3.
Mem. Inst. Oswaldo Cruz ; 104(supl.1): 301-310, July 2009. ilus
Article Dans Anglais | LILACS | ID: lil-520902

Résumé

Chagas disease, which is caused by the intracellular parasite Trypanosoma cruzi, is a neglected illness with 12-14 million reported cases in endemic geographic regions of Latin America. While the disease still represents an important public health problem in these affected areas, the available therapy, which was introduced more than four decades ago, is far from ideal due to its substantial toxicity, its limited effects on different parasite stocks, and its poor activity during the chronic phase of the disease. For the past 15 years, our group, in collaboration with research groups focused on medicinal chemistry, has been working on experimental chemotherapies for Chagas disease, investigating the biological activity, toxicity, selectivity and cellular targets of different classes of compounds on T. cruzi. In this report, we present an overview of these in vitro and in vivo studies, focusing on the most promising classes of compounds with the aim of contributing to the current knowledge of the treatment of Chagas disease and aiding in the development of a new arsenal of candidates with anti-T. cruzi efficacy.


Sujets)
Animaux , Humains , Maladie de Chagas/traitement médicamenteux , Trypanocides/usage thérapeutique , Trypanosoma cruzi/effets des médicaments et des substances chimiques , Naphtoquinones/composition chimique , Naphtoquinones/pharmacologie , Naphtoquinones/usage thérapeutique , Pentamidine/composition chimique , Pentamidine/pharmacologie , Pentamidine/usage thérapeutique , Propolis/composition chimique , Propolis/pharmacologie , Propolis/usage thérapeutique , Trypanocides/composition chimique , Trypanocides/pharmacologie
4.
Rev. Inst. Med. Trop. Säo Paulo ; 49(4): 257-260, Jul.-Aug. 2007. graf, tab
Article Dans Anglais | LILACS | ID: lil-460235

Résumé

To date, there are no vaccines against Leishmania, and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs of choice used for leishmaniasis therapy are significantly toxic, expensive and with a growing frequency of refractory infections. Because of these limitations, a combination therapy is the better hope. This work demonstrates that the essential oil from Chenopodium ambrosioides shows a synergic activity after incubation in conjunction with pentamidine against promastigotes of Leishmania amazonensis. However, an indifferent effect has been found for combinations of meglumine antimoniate or amphotericin B and the essential oil.


Até hoje não temos vacina contra a Leishmania e a quimioterapia é a indicação para o controle desta doença. Os remédios que hoje utilizamos são tóxicos e muito caros e além disso o resultado não é sempre o desejado. Por isso, uma terapia de combinação é a melhor opção. Este trabalho mostra que o óleo de essência de C. ambrosioides tem atividade sinérgica junto com a pentamidina sobre os promastigotas de L. amazonensis, diferente do resultado da combinação de antimônio de meglumine e anfotericina B e o óleo de essência.


Sujets)
Animaux , Souris , Antiprotozoaires/pharmacologie , Chenopodium ambrosioïdes/composition chimique , Leishmania/effets des médicaments et des substances chimiques , Méglumine/pharmacologie , Huile essentielle/pharmacologie , Composés organométalliques/pharmacologie , Huiles végétales/pharmacologie , Amphotéricine B/pharmacologie , Synergie des médicaments , Tests de sensibilité parasitaire , Pentamidine/pharmacologie
5.
Article Dans Anglais | IMSEAR | ID: sea-23710

Résumé

Major therapeutic obstacles in the treatment of visceral leishmaniasis (VL) include the alarming increase in antimonial unresponsiveness especially in Bihar, India and relapses in HIV-Leishmania co-infected patients. The therapeutic armamentarium for VL is currently plagued with several limitations as the available drugs are toxic, majority are effective only parenterally and need to be administered for extended periods. The first orally effective drug, miltefosine has been approved for treating VL. In antimony refractory zones, pentavalent antimony has been largely replaced by amphotericin B deoxycholate, but prolonged hospitalization, toxic effects, and requirement for monitoring greatly hamper its widespread application in endemic regions. Lipid formulations of amphotericin B, a remarkable advance in amphotericin B therapy, have greatly reduced toxicity enabling large doses to be delivered over a short period. Even a single dose treatment with liposomal amphotericin B cures > 90 per cent patients; however, the stumbling block is its prohibitive cost that precludes its widespread accessibility in endemic countries. Studies using paromomycin in VL are encouraging, and judging by the preliminary results of a recently concluded phase III trial, it could be an extremely useful and affordable antileishmanial drug. Other orally effective drugs include the azoles and allopurinol but these have met with limited success owing to either poor efficacy or unacceptable toxicity. Sitamaquine has undergone limited evaluation, and the data suggest effective antileishmanial activity; its role has to be delineated for which additional developmental studies are proposed. This review highlights the progress made in the treatment of VL, including the multiple mechanisms of action of antileishmanial drugs with a view to enable the researcher to undertake the challenge of providing affordable and effective chemotherapy.


Sujets)
Administration par voie orale , Amphotéricine B/pharmacologie , Animaux , Gluconate d'antimoine et de sodium/pharmacologie , Antinéoplasiques/pharmacologie , Antiprotozoaires/pharmacologie , Humains , Facteurs immunologiques , Leishmania/métabolisme , Leishmaniose viscérale/traitement médicamenteux , Pentamidine/pharmacologie
6.
An. méd. Asoc. Méd. Hosp. ABC ; 39(4): 149-56, oct.-dic. 1994. tab
Article Dans Espagnol | LILACS | ID: lil-143139

Résumé

Ante el aumento progresivo de nuevos casos del síndrome de inmunodeficiencia adquirida (SIDA) en México, presentamos esta revisión de los medicamentos y sustancias que actualmente se encuentran en diversas fases de investigación clínica para el tratamiento de esta infección que, sin duda, es la pandemia más importante de la segunda mitad del siglo veinte. También revisamos las indicaciones en los pacientes con SIDA. Asimismo, se incluyen los medicamentos adyuvantes en el tratamiento de las complicaciones de la infección, su uso y efectos adversos, así como sus interacciones medicamentosas


Sujets)
Humains , Antifongiques/usage thérapeutique , Ganciclovir/administration et posologie , Pentamidine/pharmacologie , Syndrome d'immunodéficience acquise/épidémiologie , Syndrome d'immunodéficience acquise/traitement médicamenteux , Zidovudine/pharmacocinétique , Zidovudine/usage thérapeutique
8.
Acta physiol. pharmacol. latinoam ; 38(2): 167-80, 1988. ilus
Article Dans Espagnol | LILACS | ID: lil-80441

Résumé

La administración intraperitoneal del DSP4 en roedores adultos, inhibe la captación de la 3H-NA exógena y reduce el contenido endógeno de NA en el sistema nervioso central y en la captación noradrenérgica desipramina, con el precursor de la NA, la 1-dopa o con inhibidores de la MAO B, previene los efectos neurotóxicos del DSP4. Con el objeto de investigar el mecanismo por el cual DSP4 reduce el contenido endógeno de NA, la liberación del neurotransmisor inducida por despolarización con K+, fue estudiada en cortes de la corteza cerebral de la rata, un tejido sensible a la acción neurotóxica del DSP4. La incubación con DSP4 (10 micromol/1) indujo un aumento de la liberación de NA espontánea y la inducida por estimulación con el K+. En medio libre de Ca++ sólo se incrementó la liberación espontánea. La potenciación de la liberación de NA inducida por el K+ parece estar relacionada con los mecanismos alfa2 adrenérgicos, dado que no se observa aditividad entre la potenciación producida por el antagonista alfa 2 yohimbina y el DSP4. Sin embargo, esta potenciación a través de mecanismos presinápticos no parece estar involucrada en la depleción desarrollada por el neurotóxico, dado que los tratamientos realziados con drogas con afinidad adrenérgicas son ineficaces para previnir la depleción noradrenérgica por el DSP4 en la corteza cerebral. Los resultados obtenidos en el conducto deferente avalan esta hipótesis, dado que en este tejido resistente al efecto deplecionante del DSP4, el compuesto t


Sujets)
Rats , Animaux , Mâle , Femelle , Benzylamines/pharmacologie , Norépinéphrine/métabolisme , Récepteurs adrénergiques , Terminaisons nerveuses , Clonidine/pharmacologie , Cortex cérébral , Pentamidine/pharmacologie , Potassium/pharmacologie , Lignées consanguines de rats , Activation chimique , Débit sécrétoire , Terminaisons nerveuses , Conduit déférent/effets des médicaments et des substances chimiques , Yohimbine/pharmacologie
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