ABSTRACT
Meglumine antimoniate (MA) and sodium stibogluconate are pentavalent antimony (SbV) drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous). Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h) and a slow (t1/2 >> 24 h) elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain). The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies.
Subject(s)
Animals , Male , Antimony/analysis , Antiprotozoal Agents/pharmacokinetics , Meglumine/pharmacokinetics , Organometallic Compounds/pharmacokinetics , Antiprotozoal Agents/administration & dosage , Dose-Response Relationship, Drug , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage , Rats, Wistar , Time Factors , Tissue DistributionABSTRACT
The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Our objective was to assess factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard and alternative treatment schemes with meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL), in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods were used for adherence monitoring: counting of vial surplus, monitoring card, Morisky test and modified Morisky test (without the question regarding the schedule); we observed 82.1% (vial return), 86.0% (monitoring card), 66.7% (Morisky test) and 86.0% (modified Morisky test) adherence. There was a strong correlation between the method of vial counting and the monitoring card and modified Morisky test. A significant association was observed between greater adherence to treatment and low dose of MA, as well as with a lower number of people sleeping in the same room. We recommend the use of the modified Morisky test to assess adherence to treatment of CL with MA, because it is a simple method and with a good performance, when compared to other methods.
O desfecho favorável ao tratamento de uma enfermidade é influenciado pela adesão à terapia. Objetivamos avaliar fatores associados à adesão ao tratamento dos pacientes incluídos em ensaio clínico de equivalência entre o esquema de tratamento padrão e alternativos com antimoniato de meglumina (AM) no tratamento da leishmaniose cutânea (LC) no estado do Rio de Janeiro. Entre 2008 e 2011, 57 pacientes com LC foram entrevistados através de questionário para coleta de dados socioeconômicos. Para monitorização da adesão foram utilizados os seguintes métodos: contagem de ampolas excedentes, cartão de acompanhamento, teste de Morisky e teste de Morisky modificado (sem a pergunta referente ao horário). Observou-se adesão de 82,1% (devolução de ampolas), 86,0% (cartão de acompanhamento), 66,7% (teste de Morisky) e 86,0% (teste de Morisky modificado). Houve forte concordância entre o método contagem de ampolas e cartão de acompanhamento, bem como teste de Morisky modificado. Verificou-se associação significativa entre maior adesão ao tratamento e baixa dose de AM, bem como com menor número de pessoas dormindo no mesmo quarto. Recomendamos a utilização do teste de Morisky modificado na avaliação da adesão ao tratamento da LC com AM por ser método simples e com bom desempenho quando comparado aos outros testes.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antiprotozoal Agents/administration & dosage , Leishmaniasis, Cutaneous/drug therapy , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage , Patient Compliance/statistics & numerical data , Socioeconomic FactorsABSTRACT
Background & objectives: Several plant products have been tested and found to possess antileishmanial activity. The present study was undertaken to establish whether methanolic extract of Allium sativum Linn has antileishmanial activity in comparison to standard drugs. Methods: Methanolic extract of A. sativum bulbs was screened for in vitro and in vivo antileishmanial activity against Leishmania major strain (NLB 145) and L. donovani strain (NLB 065). Pentostam® and Amphotericin B® were used as standard drugs. BALB/c mice and golden hamsters (Mesocricetus auratus) were used in in vivo studies on L. major and L. donovani respectively. Results: The extract exhibited very low cytotoxicity (IC50 >450 μg/ml) against Vero cells. The extract had significantly better (p <0.001) leishmanicidal activity against both species (IC50 34.22 μg/ml to L. major, 37.41 μg/ml to L. donovani) than Pentostam. However, the activity was significantly lower (p <0.001) than that of Amphotericin B against both the species. At a concentration of 250 μg/ml, the extract induced the production of 60 μM of nitric oxide, a ten-fold up-regulation in activated macrophages. The multiplication indices for L. major amastigotes treated in 100 μg/ml were significantly different (p <0.05). Treatment with the extract, daily for 28 days led to a significant reduction (p <0.05) in footpad swelling in BALB/c mice; similar activity noticed in the treatment with standard drugs. The Leishman-Donovan Units (LDU) for the extract treated animals were significantly higher (p <0.05) than those of standard drugs, but lower compared to the negative control. Interpretation & conclusion: Since the mechanism of action for the methanolic extract is apparently immunomodulatory, garlic compounds could be purified and tried as complementary medicine in the management of leishmaniases.
ABSTRACT
La leishmaniosis es una enfermedad infecciosa parasitaria, endémica, de distribución mundial, que en Venezuela se presenta como leishmaniosis tegumentaria americana (cutánea localizada, cutáneomucosa y cutáneo difusa) además de la forma visceral (kala azar). La variedad cutánea localizada representa el 90 por ciento de los casos atendidos en la consulta de Endemias Rurales del Instituto de Medicina Tropical y en los Servicios de Pediatría Médica y Enfermedades Infecciosas del Adulto del Hospital Universitario de Caracas, y la mayoría son tratados ambulatoriamente con antimoniato de meglumina. En algunas situaciones clínicas es necesaria la hospitalización. Se describen ocho casos hospitalizados: 1) niña de dos años con leishmaniosis cutánea que había recibido inmunoterapia para la parasitosis; 2) paciente de 59 años con leishmaniosis de la mucosa nasal; 3) paciente de 64 años con úlcera de los chicleros en el pabellón auricular; 4) paciente de 36 años con falla terapéutica a la meglumina, quien había recibido inmunoterapia para leishmaniosis; 5) paciente de 59 años alcohólico, con ulceración extensa de cinco años de evolución; 6) mujer de 83 años con leishmaniosis cutánea en miembros inferiores; 7) paciente con leishmaniosis de la mucosa nasal y SIDA; 8) paciente de 37 años con kala azar. Se analizan las razones para la hospitalización y las dosis de antimoniato de meglumina empleadas para la solución terapéutica
Leishmaniasis is an endemic parasitic infectious disease of worldwide distribution. In Venezuela the main characteristics correspond to american tegumentary leishmaniasis (cutaneous localized, cutaneous-mucous, cutaneous diffuse) and visceral leishmaniasis (kala azar). The localized cutaneous variety represents 90 percent of the cases attended at the ambulatory medical clinic for rural endemic diseases at the Tropical Medicine Institute, Pediatric and Adult services for Infectious Diseases at the Universitary Hospital of Caracas, and these patients are treated with pentavalent antimonials. In some clinical conditions hospitalization is required. We describe eight cases of patients treated under hospitalization. Case 1) a two year old girl with cutaneous leishmaniasis who had received immunotherapy for this parasitic disease; case 2) fifty nine year old female with nasal leishmaniasis; case 3) sixty four year old male with a rubber tappers ulcer in the ear; case 4) thirty six year old male with treatment failure to pentavalent antimonials having received immunotherapy for leishmaniasis; case 5) fifty nine year old male alcoholic patient, with extended ulcer of five years evolution; case 6) eighty three year old female with cutaneous leishmanisis in the legs; case 7) thirty three year old male with leishmaniasis of the nasal mucosa and AIDS; case 8) thirty seven year old male with kala azar. We discuss the reasons for hospitalization and the dosage of pentavalent antimonials administered
Subject(s)
Humans , Male , Female , Skin Diseases, Infectious/diagnosis , Skin Diseases, Infectious/drug therapy , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/drug therapy , Tropical MedicineABSTRACT
La leishmaniosis tegumentaria americana es un problema de salud en el medio rural venezolano. La Cátedra de Medicina Tropical (UCV) y el Hospital Universitario de Caracas reciben pacientes con diagnóstico presuntivo, se realiza el diagnóstico de certeza y son tratados ambulatoria u hospitalariamente con antimoniato de meglumina en series terapéuticas de 10 días, a dosis de 3 000 mg/día a 4 500 mg/día. Se evalúan los resultados de 221 pacientes, la mayoría adultos masculinos, con úlcera única en miembros inferiores, procedentes del medio rural del Estado Miranda. Predominó la variedad cutánea localizada, seguida de la cutáneo mucosa con 4 pacientes y cutáneo difusa con 3. Hubo cicatrización de las úlceras y desaparición de los nódulos cutáneos, excepto en 1 paciente (0,3 por ciento) que requirió anfotericina B por falla terapéutica. En el estudio participan estudiantes del curso regular de la cátedra, integrantes del programa: docencia en medicina tropical basada en publicaciones periódicas
American tegumentary leishmaniasis (ATL) is a health problem in the rural areas of Venezuela. Patients are referred to the Tropical Medicine Department (UCV) and to the University Hospital of Caracas with presumptive diagnosis of the disease, are studied to confirm the diagnosis and treated with antimoniate of meglumine in 10 days course at dose of 3 000 mg./day to 4 500 mg./day according to complications as outpatients or hospitalized. We report the results of 221 patients treated, mostly male adults from the rural area of the Miranda state with a sole ulcer in the limbs. Among the clinical presentation the cutaneous-localized form was predominating, followed by the localized muco-cutaneous with 4 and cutaneous-diffuse variety with 3. They responded with healing of the ulcers and disappearance of skin nodules, except one (0.3 percent) who required anfotericine B due to lack of response to meglumine therapy. In this investigation there was the participation of students from the Tropical Medicine course: learning based on periodic publications with students
Subject(s)
Humans , Male , Adult , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/therapy , Meglumine/therapeutic use , Tropical MedicineABSTRACT
Os autores relatam um caso de leishmaniose cutâneo-mucosa em uma paciente de 89 anos, diabética e hipertensa, tratada inicialmente com alopurinol por 10 meses não havendo cicatrização das lesões. Posteriormente, recebeu antimoniato de N-metil glucamina (glucantime) por 4 dias, na dose total de 2.380mg do Sbv, mas desenvolveu cardiotoxicidade e hipocalemia, sendo suspenso o tratamento, entretanto, evoluiu com regressão clínica total das lesões, apesar de ter recebido pequena dose desta medicação.
The authors report a case of a 89 years-old woman with mucocutaneous leishmaniasis and previous diabetes mellitus and high blood pressure, who had been treated with allopurinol for 10 months without healing of lesions. Afterwards, she has been treated with meglumine antimonate, [quot ]glucantime[quot ] for 4 days, with a total dose 2,380 mg of Sbv, but developed cardiac side effects and hypokalemia, hence the treatment was withdrawn. However, this patient developed total clinical regression of lesions, in spite of she has been received low dose of this drug.