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Rev. bras. parasitol. vet ; 28(4): 605-612, Oct.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1057981


Abstract Eimeriosis is a global poultry health problem. In the current study, we investigated the role of Salvadora persica leaf extracts (SE) against murine eimeriosis induced by Eimeria papillata. The infection induced an oocyst output of 6242 ± 731 oocysts/g feces. After treatment with 300 mg⁄kg SE, the oocysts expelled in feces decreased by approximately 3-fold. In addition, the total number of E. papillata in the parasitic stage decreased in the jejunum of mice after treatment with SE. In addition, SE significantly reduced the number of apoptotic cells by approximately 2-fold in the infected jejunum. SE ameliorated the changes in glutathione, malondialdehyde, and catalase due to E. papillata infection. Finally, SE regulated the cytokine genes, interleukin (IL)-1β, IL-6, interferon-γ, and tumor necrosis factor-α, and the apoptotic genes, B-cell lymphoma-2, Bax, and Caspase-3. SE protects the jejunum from E. papillata induced injury and may have potential therapeutic value as a food additive during eimeriosis.

Resumo A eimeriose é um problema global de saúde avícola. No presente estudo, investigou-se o papel dos extratos de folhas de Salvadora persica (SE) contra a eimeriose murina induzida por Eimeria papillata. A infecção induziu uma produção de oocistos de 6242 ± 731 oocistos/g de fezes. Após o tratamento com 300 mg⁄kg SE, os oocistos eliminados nas fezes diminuíram em aproximadamente 3 vezes. Além disso, o número total de E. papillata no estágio parasitário diminuiu nos jejunos de camundongos após o tratamento com SE. Da mesma forma, o SE reduziu significativamente o número de células apoptóticas em aproximadamente 2 vezes no jejuno infectado. O estudo mostrou que o SE melhorou as alterações na glutationa, malonaldeído e catalase devido à infecção por E. papillata. Finalmente, o SE regulou os genes das citocinas, interleucina (IL) -1β, IL-6, interferon-γ e fator de necrose tumoral α, e os genes apoptóticos, linfoma-2, Bax e Caspase-3. Assim, o SE protegeu os jejunos das lesões induzidas por E. papillata e pode ter potencial valor terapêutico como aditivo alimentar durante a eimeriose.

Animais , Masculino , Camundongos , Extratos Vegetais/farmacologia , Coccidiose/parasitologia , Salvadoraceae/química , Eimeria/efeitos dos fármacos , Fezes/parasitologia , Antiprotozoários/farmacologia , Contagem de Ovos de Parasitas , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Antiprotozoários/isolamento & purificação
An. bras. dermatol ; 94(3): 355-357, May-June 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1011111


Abstract: Pentavalent antimonials are the first-line drug treatment for American tegumentary leishmaniasis. We report on a patient with chronic renal failure on hemodialysis who presented with cutaneous lesions of leishmaniasis for four months. The patient was treated with intravenous meglumine under strict nephrological surveillance, but cardiotoxicity, acute pancreatitis, pancytopenia, and cardiogenic shock developed rapidly. Deficient renal clearance of meglumine antimoniate can result in severe toxicity, as observed in this case. These side effects are related to cumulative plasma levels of the drug. Therefore, second-line drugs like amphotericin B are a better choice for patients on dialysis.

Humanos , Masculino , Adulto , Leishmaniose Cutânea/complicações , Leishmaniose Cutânea/tratamento farmacológico , Insuficiência Renal Crônica/complicações , /efeitos adversos , Antiprotozoários/efeitos adversos , Brasil , Anfotericina B/uso terapêutico , Diálise Renal , Leishmaniose Cutânea/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Antiprotozoários/uso terapêutico
An. bras. dermatol ; 94(1): 9-16, Jan.-Feb. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-983744


Abstract: Disseminated leishmaniasis is a severe and emerging form of American tegumentary leishmaniasis. Disseminated leishmaniasis is defined by the presence of more than 10 polymorphic cutaneous lesions, distributed over more than two noncontiguous parts of the body. Nasal mucosal involvement is observed in almost half of cases. Disseminated leishmaniasis patients present with a decreased production of Th1 cytokines in the peripheral blood due to the attraction of leishmania- activated T cells to the multiple cutaneous lesions. Disseminated leishmaniasis development is poorly understood and is related to a complex network involving environmental, host immune response, and parasite factors, in which L. braziliensis polymorphism plays an important role. Disseminated leishmaniasis is a challenging disease to cure, presenting a high failure rate of 75% to pentavalent antimony therapy. Despite its importance and severity, this form of American tegumentary leishmaniasis has been poorly studied and documented, deserving greater attention from professionals working in endemic areas.

Humanos , Leishmania braziliensis , Leishmaniose Cutânea/patologia , Leishmaniose Cutânea/tratamento farmacológico , Anfotericina B/uso terapêutico , Resultado do Tratamento , Leishmaniose Cutânea/imunologia , Antiprotozoários/uso terapêutico
An. bras. dermatol ; 93(3): 347-355, May-June 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-949892


Abstract: BACKGROUND: Pentavalent antimonials remain as the standard drugs in the treatment of cutaneous leishmaniosis. The high cost, difficult administration, long treatment time, toxicity and increasing morbidity are factors that limit the use of these drugs. OBJECTIVES: To describe the response to radiofrequency thermotherapy in the treatment of localized cutaneous leishmaniasis in Brazil, and to evaluate its safety and tolerability. METHODS: We conducted a non-comparative open trial with a total of 15 patients confirmed to have cutaneous leishmaniasis on parasitological examination. A single radiofrequency thermotherapy session at 50ºC for 30 seconds was applied to the lesion and its edges. In patients with more than one lesion, only the largest one was treated initially. If after 30 days there was no evidence of healing, the smaller lesion was also treated with thermotherapy. Clinical cure was defined as visible healing for three months after treatment. The patients were followed-up for six months and there was no follow-up loss. RESULTS: Of all 23 lesions, only two evolved to complete healing without the need of treatment. Of 21 lesions, 18 (85.7%) achieved full healing. The main observed side effects were itching, burning sensation, pain and blisters. STUDY LIMITATIONS: Sample with a small number of patients and short follow-up. CONCLUSION: Thermotherapy can be considered a therapeutic alternative in localized cutaneous leishmaniasis, especially in cases of single cutaneous lesions and with formal contraindications to conventional treatment with pentavalent antimonials.

Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Leishmaniose Cutânea/terapia , Hipertermia Induzida/métodos , Antiprotozoários/uso terapêutico , Ondas de Rádio , Brasil , Resistência a Medicamentos , Intervalos de Confiança , Resultado do Tratamento , Leishmaniose Cutânea/patologia , Leishmaniose Cutânea/tratamento farmacológico , Estudos Controlados Antes e Depois , Hipertermia Induzida/efeitos adversos , Hipertermia Induzida/normas , Antiprotozoários/efeitos adversos
Mem. Inst. Oswaldo Cruz ; 113(2): 71-79, Feb. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-894896


BACKGROUND Despite its recognised toxicity, antimonial therapy continues to be the first-line drug for cutaneous leishmaniasis (CL) treatment. Intralesional administration of meglumine antimoniate (MA) represents an alternative that could reduce the systemic absorption of the drug and its side effects. OBJECTIVES This study aims to validate the standard operational procedure (SOP) for the intralesional infiltration of MA for CL therapy as the first step before the assessment of efficacy and safety related to the procedure. METHODS The SOP was created based on 21 trials retrieved from the literature, direct monitoring of the procedure and consultation with experts. This script was submitted to a formal computer-aided inspection to identify readability, clarity, omission, redundancy and unnecessary information (content validation). For criterion and construct validations, the influence of critical condition changes (compliance with the instructions and professional experience) on outcome conformity (saturation status achievement), tolerability (pain referred) and safety (bleeding) were assessed. FINDINGS The median procedure length was 12 minutes and in 72% of them, patients classified the pain as mild. The bleeding was also classified as mild in 96.6% of the procedures. Full compliance with the SOP was observed in 66% of infiltrations. Despite this, in 100% of the inspected procedures, lesion saturation was observed at the end of infiltration, which means that it tolerates some degree of modification in its execution (robustness) without prejudice to the result. CONCLUSIONS The procedure is reproducible and can be used by professionals without previous training with high success and safety rates.

Humanos , Injeções Intralesionais/efeitos adversos , Leishmaniose Cutânea/tratamento farmacológico , Meglumina , Antiprotozoários/administração & dosagem , Protocolos Clínicos/normas , Reprodutibilidade dos Testes
Bol. latinoam. Caribe plantas med. aromát ; 17(1): 68-83, ene. 2018. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-915131


Los aceites esenciales (AEs), pertenecientes al género Lippia, son candidatos interesantes de formulaciones tópicas en el tratamiento de la leishmaniasis cutánea (LC). El objetivo de este trabajo fue determinar el perfil toxicológico y la actividad anti-Leishmania de AEs obtenidos de plantas colombianas del género Lippia. Ratones BALB/c fueron tratados tópica u oralmente con AEs obtenidos de L. alba quimiotipo citral (AE1) y de L. origanoides quimiotipos timol (AE2), carvacrol (AE3) y felandreno (AE4). El efecto del tratamiento en la irritación de la piel, la toxicidad aguda oral, la genotoxicidad (prueba cometa y micronúcleos), los cambios en la función hepática y renal, la inducción de reacción de hipersensibilidad de contacto y en la actividad contra L. (V) panamensis y L. (V.) braziliensis fueron determinados. Todos los AEs presentaron un perfil toxicológico similar a los parámetros normales, exceptuando los aceites AE2 y AE3 los cuales fueron irritantes y presentaron algunos signos de toxicidad aguda oral al ser utilizados en altas concentraciones (concentraciones bajas no fueron tóxicas). El AE2 mostró actividad antiparasitaria en las formas parasitarias evaluadas. Concentraciones bajas de los AEs podrían utilizarse de forma segura como componentes de formulaciones farmacológicas en LC.

Essential oils (EOs) belonging to the genus Lippia are interesting candidates in pharmaceutical systems for cutaneous leishmaniasis (CL). The aim of this work was to determine both toxicological and antileishmanial activities of EOs obtained from different species of Lippia, a widely distributed Colombian plants. BALB/c mice were treated topically or orally with EOs obtained from L. alba citral chemotype (EO1) and L. origanoides thymol (EO2), carvacrol (EO3) and phellandrene (EO4) chemotypes. The skin irritation, oral acute toxicity, genotoxicity (comet assay and micronucleus test), liver and renal adverse effects, All the EOs showed a toxicological profile similar to the normal parameters, except for oils EO2 and EO3 which were irritant and showed some signs of acute oral toxicity at high concentrations (low concentration were safe). The EO2 showed antiparasitic activity. Low concentrations of the EO could be used safely as components of pharmacological formulations in CL.

Animais , Feminino , Camundongos , Óleos Voláteis/farmacologia , Leishmaniose Cutânea/tratamento farmacológico , Lippia/química , Leishmania/efeitos dos fármacos , Antiprotozoários/farmacologia , Óleos Voláteis/efeitos adversos , Colômbia , Ensaio Cometa , Dermatite de Contato/etiologia , Genotoxicidade , Camundongos Endogâmicos BALB C , Antiprotozoários/efeitos adversos
Mem. Inst. Oswaldo Cruz ; 113(9): e180200, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-955123


BACKGROUND Cutaneous leishmaniasis (CL) is a world-wide health problem which currently lacks effective, affordable and easy to use therapy. Recently, the meglumine antimoniate (MA) intralesional infiltration was included among the acceptable therapies for New World leishmaniasis. While this approach is attractive, there is currently little evidence to support its use in Americas. OBJECTIVES The aim of this study was to provide information about effectiveness and safety of a standardised MA intralesional infiltration technique for the treatment of CL. METHODS It is a single-arm phase II clinical trial conducted at a Brazilian referral centre. CL cases with parasitological confirmation presenting a maximum of three CL-compatible skin lesions were treated with weekly MA intralesional infiltration by using a validated technique, up to a maximum of eight infiltrations. RESULTS A total of 53 patients (62 lesions) were included. Overall, patients received a median of seven infiltrations (IQR25-75% 5-8) over a median treatment period of 43 days (IQR25-75% 28-52 days). The definitive cure rate at D180 was 87% (95% CI:77-96%). The majority of adverse events were local, with mild or moderate intensity. Bacterial secondary infection of the lesion site was observed in 13% of the treated patients, beside two intensity-three adverse events (hypersensitivity reactions).

Humanos , Compostos Organometálicos/administração & dosagem , Leishmaniose Cutânea/tratamento farmacológico , /uso terapêutico , Injeções Intralesionais , Antiprotozoários/efeitos adversos
Pesqui. vet. bras ; 37(12): 1509-1513, dez. 2017. ilus
Artigo em Português | LILACS, VETINDEX | ID: biblio-895387


Aceturato de diminazeno é um fármaco quimioterápico sintético comumente usado na medicina veterinária para o tratamento de doenças causadas por parasitos hematozoários. Entretanto, seu uso pode levar a efeitos colaterais, como alterações neurológicas graves e morte. A criação de camelídeos é uma atividade recente no Brasil, fazendo-se necessário conhecer mais sobre as doenças que acometem essas espécies. De dez camelídeos (seis lhamas e quatro alpacas) da propriedade, seis tiveram sinais clínicos e, destes, apenas uma lhama com manifestações leves recuperou-se. Os sinais clínicos incluíam apatia, andar cambaleante, fraqueza, sialorreia, cabeça baixa e pendida lateralmente, dificuldade em levantar e dispneia, observados a partir de 18 horas após o uso do medicamento. À necropsia e ao exame histopatológico foram observadas alterações de encefalopatia hemorrágica bilateral e simétrica, mais graves em tronco encefálico e tálamo. Este trabalho descreve as principais lesões observadas em um surto de intoxicação por diminazeno em alpacas (Lama pacos) e lhamas (Lama glama) e alerta criadores e veterinários sobre o risco de intoxicação por aceturato de diminazeno em camelídeos sul americanos.(AU)

Diminazene aceturate is a synthetic chemotherapeutic drug commonly used in veterinary medicine for the treatment of diseases caused by hematozoan parasites. However, side effects as severe neurological disorders and death can occur. The raising of american camelids is a recent activity in Brazil, requiring knowledge about diseases that affect these species, in order to avoid misguided conducts. In a herd of ten camelids (six llamas and four alpacas) six showed clinical signs and five died; only a llama with mild signs recovered. The clinical signs included apathy, difficulty to stand up, staggering gait, weakness, down head and drooping the head laterally, dyspnea and drooling of saliva, observed from 18 hours after use of the drug. At necropsy and histopathological examination was found bilateral and symmetrical hemorrhagic encephalopathy, more severe in brainstem and thalamus. This paper describes the main lesions observed in an outbreak of diminazene aceturate poisoning in alpacas (Lama pacos) and llamas (Lama glama) and alert breeders and veterinarians about the risk of poisoning by this drug in american camelids.(AU)

Animais , Camelídeos Americanos , Diminazena/efeitos adversos , Diminazena/toxicidade , Doenças do Sistema Nervoso/veterinária , Antiprotozoários/efeitos adversos
Rev. Soc. Bras. Clín. Méd ; 15(2): 116-119, 20170000. ilus
Artigo em Português | LILACS | ID: biblio-875565


Apesar de não haver caso autóctone na Região Sudeste, a leishmaniose visceral é encontrada em pacientes que migram de regiões endêmicas. Como é uma doença que, se não reconhecida e conduzida adequadamente, apresenta alta mortalidade, realizamos uma revisão bibliográfica e destacamos, com o relato deste caso, a importância de a incluirmos no diagnóstico diferencial de hepatoesplenomegalia febril ainda na avaliação clínica inicial, pois o retardo no diagnóstico piora o prognóstico e a sobrevida do paciente, sendo sumária a introdução de terapêutica apropriada o mais breve possível.(AU)

Although there is no autochthonous case finding in the Southeast Region, visceral leishmaniasis is found in patients migrating from endemic areas. Because it is a disease that, if not properly recognized and treated, presents high mortality, we performed a bibliographic review and highlight, with the report of this case, the importance of including it in the differential diagnosis of febrile hepatosplenomegaly in the initial clinical evaluation. The late diagnosis worsens the patient's prognosis and survival, and the introduction of appropriate therapeutics should be made as soon as possible.(AU)

Humanos , Masculino , Adulto Jovem , Antiprotozoários/uso terapêutico , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Hepatopatias Parasitárias/diagnóstico , Esplenomegalia/diagnóstico , Brasil/epidemiologia , Diagnóstico Diferencial
Artigo em Inglês | LILACS | ID: biblio-842780


ABSTRACT The authors report a case of disseminated cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis, in a 55 years old patient with 1,119 lesions distributed throughout the body. The patient resides in Sabáudia municipality, North of Paraná State, Southern Brazil, where there was no previous report of this form of leishmaniasis. Treatment with meglumine antimoniate was successful, although the diagnosis was made only five months later.

Humanos , Masculino , Pessoa de Meia-Idade , Leishmania braziliensis , Leishmaniose Cutânea/diagnóstico , Antiprotozoários/uso terapêutico , Brasil , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico
Mem. Inst. Oswaldo Cruz ; 111(8): 512-516, Aug. 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-789001


Although intralesional meglumine antimoniate (MA) infiltration is considered an option for cutaneous leishmaniasis (CL) therapy and is widely used in the Old World, there have been few studies supporting this therapeutic approach in the Americas. This study aims to describe outcomes and adverse events associated with intralesional therapy for CL. This retrospective study reviewed the experience of a Brazilian leishmaniasis reference centre using intralesional MA to treat 31 patients over five years (2008 and 2013). The median age was 63 years (22-86) and the median duration time of the lesions up to treatment was 16 weeks. In 22 patients (71%), intralesional therapy was indicated due to the presence of contraindications or previous serious adverse events with systemic MA. Other indications were failure of systemic therapy or ease of administration. Intralesional treatment consisted of one-six infiltrations (median three) for a period of up to 12 weeks. The initial (three months) and definitive (six months) cure rates were 70.9% and 67.7%, respectively. Most patients reported mild discomfort during infiltration and no serious adverse events were observed. In conclusion, these results show that the intralesional MA efficacy rate was very similar to that of systemic MA treatment, and reinforce the need for further studies with adequate design to establish the efficacy and safety of this therapeutic approach.

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Antiprotozoários/administração & dosagem , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/administração & dosagem , Compostos Organometálicos/administração & dosagem , Antiprotozoários/efeitos adversos , Injeções Intralesionais , Leishmaniose Cutânea/patologia , Meglumina/efeitos adversos , Compostos Organometálicos/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
An. bras. dermatol ; 91(3): 365-367, graf
Artigo em Inglês | LILACS | ID: lil-787294


Abstract: We report an imported case of cutaneous leishmaniasis in a 37-year-old man from Saudi Arabia caused by Leishmania major. He presented with non-healing nodulo-ulcerative lesions with a "volcanic crater" on the lower limbs. It was clearly cutaneous leishmaniasis - a rare disease in China - as reflected by the patient's clinical history, the lesions' morphology, histopathological examination, culture and PCR analysis of the lesions. The patient was completely cured after two cycles of sodium stibogluconate treatment. This case report demonstrates that dermatologists should be aware of sporadic cutaneous leishmaniasis cases in non-endemic areas.

Humanos , Masculino , Adulto , Leishmaniose Cutânea/parasitologia , Leishmania major , Arábia Saudita , China/etnologia , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Gluconato de Antimônio e Sódio/uso terapêutico , Emigrantes e Imigrantes , Úlcera da Perna/parasitologia , Antiprotozoários/uso terapêutico
Mem. Inst. Oswaldo Cruz ; 111(3): 147-154, Mar. 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-777370


The polar hydroethanolic extract from Selaginella sellowii(SSPHE) has been previously proven active on intracellular amastigotes (in vitro test) and now was tested on hamsters infected with Leishmania (Leishmania) amazonensis (in vivo test). SSPHE suppressed a 100% of the parasite load in the infection site and draining lymph nodes at an intralesional dose of 50 mg/kg/day × 5, which was similar to the results observed in hamsters treated with N-methylglucamine antimonate (Sb) (28 mg/Kg/day × 5). When orally administered, SSPHE (50 mg/kg/day × 20) suppressed 99.2% of the parasite load in infected footpads, while Sb suppressed 98.5%. SSPHE also enhanced the release of nitric oxide through the intralesional route in comparison to Sb. The chemical fingerprint of SSPHE by high-performance liquid chromatography with diode-array detection and tandem mass spectrometry showed the presence of biflavonoids and high molecular weight phenylpropanoid glycosides. These compounds may have a synergistic action in vivo. Histopathological study revealed that the intralesional treatment with SSPHE induced an intense inflammatory infiltrate, composed mainly of mononuclear cells. The present findings reinforce the potential of this natural product as a source of future drug candidates for American cutaneous leishmaniasis.

Animais , Cricetinae , Masculino , Antiprotozoários/farmacologia , Leishmania/efeitos dos fármacos , Extratos Vegetais/química , Selaginellaceae/química , Administração Oral , Antiprotozoários/isolamento & purificação , Biflavonoides/análise , Cromatografia Líquida de Alta Pressão , Drenagem , Pé/parasitologia , Glicosídeos/química , Infusões Intralesionais , Leucócitos Mononucleares/parasitologia , Macrófagos/parasitologia , Meglumina/administração & dosagem , Óxido Nítrico/análise , Compostos Organometálicos/administração & dosagem , Carga Parasitária , Extratos Vegetais/administração & dosagem , Solventes , Espectrometria de Massas em Tandem
Recife; s.n; 2016. 95 p. ilus, graf, tab.
Tese em Português | LILACS | ID: biblio-870270


As leishmanioses constituem um grupo de doenças crônicas causadas por protozoários pertencentes ao gênero Leishmania. Tendo em vista a complexidade e ineficácia dos tratamentos atuais, o desenvolvimento de novas drogas menos tóxicas ainda é uma necessidade. Na prospecção de possíveis agentes quimioterápicos contra as leishmanioses, as lectinas apresentam-se como candidatos promissores por apresentarem um amplo espectro de atividades biológicas. No presente trabalho nós investigamos o potencial leishmanicida e imunomodulador da lectina Onil. Nossos resultados demonstraram que a Onil apresentou baixa toxidade sobre células do exsudato peritoneal (CEP) de camundongos (CC50= 317,5 ± 0,6 µg/mL), foi efetiva ao inibir o crescimento de formas promastigotas de L. braziliensis (IC50=150,58± 0,78 µg/mL), mostrou-se mais seletiva para o parasito do que para célula do hospedeiro (ISe=2,1). No entanto, não foi capaz de inibir a sobrevivência das amastigotas no interior das CEPs. A lectina Onil causou alterações ultraestruturais no flagelo, bem como mostrou um efeito sobre a divisão celular de formas promastigotas. A marcação das células tratadas com Anexina V (AV) e Iodeto de Propídio (IP) mostrou uma pequena subpopulação de células apresentava marcação para AV/IP compatíveis com o processo de morte celular por necrose/apoptose tardia. A marcação das células controles e tratadas com Onil com Rho 123 revelou que na grande maioria das células o potencial de membrana mitocondrial foi preservado. O tratamento com a lectina (75-300 µg/mL) não alterou significativamente a produção de NO e não induziu alterações na produção de citocinas em CEPs infectadas L. braziliensis. Por outro lado, uma intensa produção de citocinas associadas aos perfis Th1, Th2 e Th17 foi observada em CEPs não infectadas tratadas com 30 µg/mL da Onil. Nossos dados apontam para uma possível utilização da Onil como agente adjuvante ou como carreadora de drogas para o tratamento da leishmaniose cutânea

Leishmaniasis comprises a group of disease caused by protozoa belonging to the Leishmaniagenus. Taking in account the complexity and inefficiency of current treatments against leishmaniasis, the development of new, less toxic drugs is still needed. In a search of potential chemotherapeutic agents against leishmaniasis, lectins presented as promising candidates because for presenting a broad spectrum of biological activities. In this regard, in the present study we investigated the leishmanicidal and immunomodulatory activities of Onil in vitro. Our results demonstrated that Onil presented low toxicity to mice peritoneal exudate cells (PEC) (CC50= 317.5 ± 0.6 μg / mL), was effective to inhibit the growth of promastigotes of Leishmania braziliensis (IC50= 150.58 ± 0.78 μg / mL) and was shown to be more selective for the parasite than to the host cell, with SeI=2.1...

Camundongos , Antiprotozoários/farmacologia , Leishmaniose Cutânea , Lectinas/toxicidade , Lectinas/uso terapêutico , Leishmania braziliensis , Leishmania braziliensis/ultraestrutura , Antiprotozoários/toxicidade , Antiprotozoários/uso terapêutico , Ciclídeos/sangue , Exsudatos e Transudatos
Mem. Inst. Oswaldo Cruz ; 110(8): 1024-1034, Dec. 2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-769826


The herbaceous shrub Tetradenia riparia has been traditionally used to treat inflammatory and infectious diseases. Recently, a study showed that T. riparia essential oil (TrEO) obtained in summer has antileishmanial effects, although these results could be influenced by seasonal variation. This study evaluated the activity of the TrEO obtained in different seasons against Leishmania (Leishmania) amazonensis, in vitro and in vivo. The compounds in the TrEO were analysed by gas chromatography-mass spectrometry; terpenoids were present and oxygenated sesquiterpenes were the majority compounds (55.28%). The cytotoxicity and nitric oxide (NO) production were also tested after TrEO treatment. The TrEO from all seasons showed a 50% growth inhibitory concentration for promastigotes of about 15 ng/mL; at 30 ng/mL and 3 ng/mL, the TrEO reduced intracellular amastigote infection, independently of season. The TrEO from plants harvested in summer had the highest 50% cytotoxic concentration, 1,476 ng/mL for J774.A1 macrophages, and in spring (90.94 ng/mL) for murine macrophages. NO production did not change in samples of the TrEO from different seasons. The antileishmanial effect in vivo consisted of a reduction of the parasite load in the spleen. These results suggest that the TrEO has potential effects on L. (L.) amazonensis, consonant with its traditional use to treat parasitic diseases.

Animais , Feminino , Antiprotozoários/farmacologia , Lamiaceae/química , Leishmania/efeitos dos fármacos , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Antiprotozoários/isolamento & purificação , Citotoxinas/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Inibidores do Crescimento/farmacologia , Técnicas In Vitro , Leishmania/classificação , Linfonodos/parasitologia , Camundongos Endogâmicos BALB C , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Óxido Nítrico/análise , Óleos Voláteis/química , Carga Parasitária , Extratos Vegetais/química , Folhas de Planta/química , Estações do Ano , Sesquiterpenos/análise , Baço/parasitologia , Fatores de Tempo
An. bras. dermatol ; 90(6): 807-813, Nov.-Dec. 2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-769514


Abstract: BACKGROUND: There have been few studies on pentamidine in the Americas; and there is no consensus regarding the dose that should be applied. OBJECTIVES: To evaluate the use of pentamidine in a single dose to treat cutaneous leishmaniasis. METHODS: Clinical trial of phase II pilot study with 20 patients. Pentamidine was used at a dose of 7 mg/kg, in a single dose. Safety and adverse effects were also assessed. Patients were reviewed one, two, and six months after the end of treatments. RESULTS: there was no difference between the treatment groups in relation to gender, age, number or location of the lesions. Pentamidine, applied in a single dose, obtained an effectiveness of 55%. Mild adverse events were reported by 17 (85%) patients, mainly transient pain at the site of applications (85%), while nausea (5%), malaise (5%) and dizziness (5%) were reported in one patient. No patient had sterile abscess after taking medication at a single dose of 7mg/kg. CONCLUSIONS: Clinical studies with larger samples of patients would enable a better clinical response of pent amidine at a single dose of 7mg, allowing the application of more powerful statistical tests, thus providing more evidences of the decrease in the effectiveness of that medication. Hence, it is important to have larger studies with new diagrams and/or new medications.

Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antiprotozoários/administração & dosagem , Benzamidinas/administração & dosagem , Leishmania guyanensis , Leishmaniose Cutânea/tratamento farmacológico , Éteres Fenílicos/administração & dosagem , Antiprotozoários/efeitos adversos , Benzamidinas/efeitos adversos , Glicemia/análise , Relação Dose-Resposta a Droga , Projetos Piloto , Éteres Fenílicos/efeitos adversos , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
Rev. Soc. Bras. Med. Trop ; 48(3): 235-242, May-Jun/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-749870


Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. It is a life-threatening disease of medical, social and economic importance in endemic areas. No vaccine is yet available for human use, and chemotherapy presents several problems. Pentavalent antimonials have been the drugs of choice to treat the disease for more than six decades; however, they exhibit high toxicity and are not indicated for children, for pregnant or breastfeeding women or for chronically ill patients. Amphotericin B (AmpB) is a second-line drug, and although it has been increasingly used to treat visceral leishmaniasis (VL), its clinical use has been hampered due to its high toxicity. This review focuses on the development and in vivo usage of new delivery systems for AmpB that aim to decrease its toxicity without altering its therapeutic efficacy. These new formulations, when adjusted with regard to their production costs, may be considered new drug delivery systems that promise to improve the treatment of leishmaniasis, by reducing the side effects and the number of doses while permitting a satisfactory cost-benefit ratio.

Animais , Cães , Humanos , Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Sistemas de Liberação de Medicamentos , Leishmaniose Visceral/tratamento farmacológico , Química Farmacêutica , Nanopartículas , Nanotecnologia
An. bras. dermatol ; 90(3,supl.1): 108-110, May-June 2015. ilus
Artigo em Inglês | LILACS | ID: lil-755735



In Brazil, visceral Leishmaniasis is caused by Leishmania chagasi. The development of cutaneous lesions in visceral leishmaniasis patients has been described in two different clinical contexts. Patients with compromised immunity can develop skin lesions as a direct consequence of a current visceral disease. Equally, patients with a history of kala-azar and progressive, immune improvement occasionally develop skin lesions as a consequence of immune reconstitution infl ammatory syndrome. These cases manifest in similar fashion to the classic form of post-kala-azar dermal Leishmaniasis. We describe different cases that exemplify these two clinical presentations.


Adulto , Humanos , Masculino , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Leishmaniose Cutânea/imunologia , Leishmaniose Visceral/imunologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Visceral/tratamento farmacológico