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1.
Rev. cient. salud UNITEPC ; 11(1): 37-48, jun. 2024.
Artículo en Español | LILACS | ID: biblio-1567248

RESUMEN

Objetivo: este estudio pretende realizar una comparación de la eficacia y los posibles efectos adversos asociados al uso de Miltefosina y Glucantime para el tratamiento de la leishmaniasis cutánea (LC) en niños. Método: se realizó una revisión sistemática de ensayos clínicos y estudios de cohortes, que evaluaran tratamientos de la LC en niños (≤12 años). Se efectuaron búsquedas estructuradas en PubMed, EMBASE, Cochrane, LILACS, Web of Science y SciELO. No se aplicaron restricciones en cuanto a etnia, país, sexo o año de publicación. Los idiomas se limitaron a inglés, español y portugués. Dos revisores independientes revisaron los artículos, extrajeron los datos y evaluaron el riesgo de sesgo. Se realizó un resumen cuantitativo de los estudios incluidos. Resultados: encontramos un total de 747 registros, que incluían 3 ensayos clínicos aleatorizados (ECA) y 1 estudio no aleatorizado. La mayoría de los artículos excluidos en la revisión de texto completo no informaban de los resultados por separado para los niños. En la LC americana (LCA), 4 estudios evaluaron la Miltefosina y el Glucantime. Su eficacia varió del 55,8 al 82,7 % y del 55 al 68,9 %, respectivamente. Conclusiones: en esta revisión sistémica y metaanálisis encontramos que la Miltefosina es mejor opción de tratamiento sistémico para CL en términos de curación clínica y menor efecto adverso al Glucantime administrado de forma sistémica, sin embargo, estas diferencias no fueron significativas.


Objective: this study aims to perform a comparison of the efficacy and potential adverse effects associated with the use of Miltefosine and Glucantime for the treatment of cutaneous leishmaniasis (CL) in children. Method: a systematic review of clinical trials and cohort studies evaluating treatments for CL in children (≤12 years) was conducted. Structured searches were performed in PubMed, EMBASE, Cochrane, LILACS, Web of Science, and SciELO. No restrictions were applied regarding ethnicity, country, gender, or year of publication. Languages were limited to English, Spanish, and Portuguese. Two independent reviewers screened articles, extracted data, and assessed the risk of bias. A quantitative summary of included studies was performed. Results: a total of 747 records were found, including 3 randomized clinical trials (RCTs) and 1 non-randomized study. Most articles excluded in the full-text review did not report results separately for children. In American CL (ACL), 4 studies evaluated Miltefosine and Glucantime. Their efficacy ranged from 55.8 to 82.7 % and from 55 to 68.9 %, respectively. Conclusions: in this systematic review and meta-analysis, we found that Miltefosine is a better systemic treatment option for CL in terms of clinical cure and fewer adverse effects compared to Glucantime administered systemically; however, these differences were not significant.


Objetivo: este estudo tem como objetivo realizar uma comparação da eficácia e dos possíveis efeitos adversos associados ao uso de Miltefosina e Glucantime para o tratamento da leishmaniose cutânea (LC) em crianças. Método: foi realizado uma revisão sistemática de ensaios clínicos e estudos de coorte que avaliaram tratamentos para LC em crianças (≤12 anos). Foram realizadas buscas estruturadas no PubMed, EMBASE, Cochrane, LILACS, Web of Science e SciELO. Não houve restrições quanto à etnia, país, sexo ou ano de publicação. Os idiomas foram limitados a inglês, espanhol e português. Dois revisores independentes revisaram os artigos, extraíram os dados e avaliaram o risco de viés. Foi feito um resumo quantitativo dos estudos incluídos. Resultados: encontramos um total de 747 registros, incluindo 3 ensaios clínicos randomizados (ECR) e 1 estudo não randomizado. A maioria dos artigos excluídos na revisão em texto completo não relatava resultados separados para crianças. Na LC americana (LCA), 4 estudos avaliaram Miltefosina e Glucantime. Sua eficácia variou de 55,8% a 82,7% e de 55% a 68,9%, respectivamente. Conclusões: nesta revisão sistemática e meta-análise, encontramos que a Miltefosina é uma melhor opção de tratamento sistêmico para LC em termos de cura clínica e menos efeitos adversos em comparação com o Glucantime administrado de forma sistêmica; no entanto, essas diferenças não foram significativas.

2.
Int J Parasitol Drugs Drug Resist ; 24: 100525, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38359731

RESUMEN

Leishmaniasis is a disease caused by Leishmania spp., affecting millions of people around the world. For decades, its treatment has been based on pentavalent antimonials, which notoriously cause toxic side effects in patients. In this study, epoxy-α-lapachone incorporated into an oil-in-water-type microemulsion (ELAP-ME) and meglumine antimoniate (MA) were assayed in monotherapy and in combination (ELAP-ME/MA) in BALB/c mice infected with Leishmania (Leishmania) amazonensis. In general, there was a reduction in paw lesion size (up to 37% reduction) and decreases of parasite loads in the footpad (∼40%) and lymph nodes (∼31%) of animals treated with ELAP-ME/MA, when compared to the non-treated control groups. Analyses of serum biochemical parameters revealed that the ELAP-ME/MA showed lower renal and hepatic toxicity when compared to MA 2-doses/week monotherapy. These findings indicate that the ELAP-ME/MA combination may be a promising approach for the treatment of cutaneous leishmaniasis.


Asunto(s)
Antiprotozoarios , Leishmania , Leishmaniasis Cutánea , Naftoquinonas , Compuestos Organometálicos , Humanos , Animales , Ratones , Antimoniato de Meglumina/uso terapéutico , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/parasitología , Meglumina/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Ratones Endogámicos BALB C
3.
Nat Prod Res ; 38(1): 16-27, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-35856479

RESUMEN

Two new eudesmane-type sesquiterpene lactones, 1ß,3α,8α-trihydroxy-11ß,13-dihydroeudesma-4(15)-en-12,6α-olide (1) and 1ß,4α,8α-trihydroxy-11ß,13-dihydroeudesma-12,6α-olide (2), and an unprecedented elemane-type sesquiterpene lactone, 1ß,2ß,8α-trihydroxy-11ß,13-dihydroelema-12,6α-olide (3) along with a known eudesmanolide artapshin (4) were isolated from Seriphidium khorassanicum. Structures were elucidated by NMR, HR-ESI-MS, and ECD spectral data analysis. The anti-protozoal activity was evaluated against Leishmania major promastigotes and amastigote-infected macrophages. They showed dose- and time-dependent activity against L. major amastigotes with IC50 values in the range of 4.9 to 25.3 µM being favourably far below their toxicity against normal murine macrophages with CC50 values ranging from 432.5 to 620.7 µM after 48 h of treatment. Compound 3 exhibited the strongest activity and the highest selectivity index (SI) with IC50 of 4.9 ± 0.6 µM and SI of 88.2 comparable with the standard drug, meglumine antimoniate (Glucantime), with IC50 and SI values of 15.5 ± 2.1 µM and 40.0, respectively.


Asunto(s)
Artemisia , Asteraceae , Sesquiterpenos , Ratones , Animales , Lactonas/farmacología , Lactonas/química , Asteraceae/química , Sesquiterpenos/farmacología , Sesquiterpenos/química , Fitoquímicos/farmacología , Componentes Aéreos de las Plantas
4.
Front Immunol ; 14: 1285943, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38106411

RESUMEN

Background: Immunosuppression is a major risk factor for the development of visceral leishmaniasis (VL). The number of patients receiving immunosuppressant drugs such as TNF antagonist (anti-TNF) and methotrexate (MTX) is increasing. In these patients, VL is more severe, their response to treatment poorer, and they are at higher risk of relapse, a consequence (largely) of the poor and inappropriate immune response they develop. Objectives: To examine the effect of immunosuppressive treatment on the host immune response and thus gain insight into the reduced efficacy of pentavalent antimonials in these patients. Experiments were performed using BALB/c mice immunosuppressed with anti-TNF or MTX, infected with Leishmania infantum promastigotes, and then treated with Glucantime® at clinical doses. Results: Immunosuppression with both agents impeded parasite elimination from the spleen and bone marrow. Low pro-inflammatory cytokine production by CD4+ and CD8+ T cells was detected, along with an increase in PD-1 and IL-10 expression by B and T cells in the immunosuppressed groups after treatment. Conclusion: The immunosuppressed mice were unable to develop specific cellular immunity to the parasite, perhaps explaining the greater risk of VL relapse seen in pharmacologically immunosuppressed human patients.


Asunto(s)
Leishmania infantum , Leishmaniasis Visceral , Leishmaniasis , Parásitos , Humanos , Animales , Ratones , Antimoniato de Meglumina/uso terapéutico , Linfocitos T CD8-positivos , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral , Modelos Animales de Enfermedad , Inmunidad Celular , Recurrencia
5.
Front Pharmacol ; 14: 1280240, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38026970

RESUMEN

Aim: This study aimed to investigate the effects of topical liposomal clarithromycin in combination with meglumine antimoniate (Glucantime®) on cutaneous leishmaniasis (CL) lesions. Methods: This pilot, randomized, double-blinded clinical trial was conducted on patients with CL lesions. Patients were randomly assigned to two groups: the first group received liposomal clarithromycin in combination with Glucantime for 28 days, while the second group received Glucantime and a placebo. Afterward, patients were followed up at 1.5, 3, and 6 months after treatment initiation and were evaluated for recovery time, induration, and size of the lesions. Results: Sixty patients with CL lesions were divided into two separate groups with 30 members each and were examined. Within-group analysis revealed that recovery time in the clarithromycin group was 26.65 ± 5.12 days, while in the placebo group, it was 32.84 ± 24.43, which was statistically insignificant (p = 0.18). Lesion size comparison in the first and last follow-ups reduced in both groups: 7.73 ± 4.31 to 0.48 ± 0.50 in the clarithromycin group (p = 0.006) and 5.47 ± 5.83 to 0.76 ± 0.88 in the placebo group (p = 0.03). Moreover, the size of lesions in the intervention group was significantly reduced compared to that in the placebo group (p = 0.02). Recognizable induration reduction was observed in the clarithromycin group (2.60 ± 0.77 to 1.0 ± 0.00). No adverse effects attributable to clarithromycin were reported. Conclusion: The administration of liposomal clarithromycin in combination with systemic Glucantime had a significant beneficial effect on reducing lesion size in leishmaniasis. Further studies on larger populations are recommended. Systematic Review Registration: https://www.irct.ir/trial/46611.

6.
Cureus ; 15(5): e39026, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37323333

RESUMEN

Cutaneous leishmaniasis can present in many different clinical forms. Diagnosis of atypical forms is often delayed. It is useful to keep in mind the diagnosis of cutaneous leishmaniasis, a mimicking disease, to reduce unnecessary treatment and patient morbidity. Erysipeloid leishmaniasis should be considered when presented as long-term erysipelas-like lesions that do not respond to antibiotics. We want to present our five patients with erysipeloid leishmaniasis, one of the atypical clinical forms.

7.
Infect Disord Drug Targets ; 23(6): e020623217598, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37278044

RESUMEN

INTRODUCTION: Cutaneous leishmaniasis (CL) is a serious health problem in some parts of the world, such as Iran. Since the use of pentavalent antimonial compounds such as meglumine antimoniate (Glucantime, MA) for the treatment of CL has side effects, naloxone as a new treatment in the footpad of Leishmania major (L. major)-infected BALB/c mice was investigated by evaluating the lesion size and the parasite burden. METHOD: The animals were infected with L. major (MRHO/IR/75/ER). 40 BALB/c mice were divided into 4 groups (10/group), and were treated as follows 39 days after L. major infection: Group 1 treated with intraperitoneal injections of MA (100 mg/kg, positive control group) daily for six weeks; Group 2 received a 100 µl injection of PBS (negative control group); Group 3 received subcutaneous (SC) injections of naloxone (10 mg/kg) daily for six weeks (Naloxone1), and Group 4 was SC injected with naloxone (10 mg/kg) weekly for six weeks (Naloxone2). The lesion size was measured using a digital caliper. RESULT: After the end of treatment, the lesion parasite burden was evaluated. As compared to the negative control group, the groups that received MA and naloxone (groups 1, 3, and 4) showed fewer parasites. Also, the naloxone-treated mice showed significantly smaller lesion sizes than the negative control group (p˂0.05), but they did not differ significantly from the MA-treated mice. CONCLUSION: Taken together, the results suggest that naloxone might be a promising and alternative treatment for CL.


Asunto(s)
Antiprotozoarios , Leishmania major , Leishmaniasis Cutánea , Animales , Ratones , Ratones Endogámicos BALB C , Leishmaniasis Cutánea/tratamiento farmacológico , Antimoniato de Meglumina/uso terapéutico , Piel , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico
8.
Adv Biomed Res ; 12: 32, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37057223

RESUMEN

Background: The present study aimed at investigating the topical effect of the combination of Plantago ovata and vinegar on the improvement of rural cutaneous leishmaniasis lesions. Materials and Methods: The present randomized double-blind controlled clinical trial was performed on 42 patients with rural skin leishmaniasis. In the case group, in addition to injecting glucantime into the lesion according to the latest national instructions, a combination of P. ovata and vinegar was applied topically twice a day for 8 weeks. In the control group, only glucantime injection into the lesion was performed for 8 weeks according to the latest national guidelines. At the end of the 1st, 2nd, 3rd, 4th, 8th, and 12th weeks after the intervention, the lesion area and improvement were evaluated and recorded. Results: The results of the present study indicated the lesion area in the case group with the mean of 0.35 ± 0.39 cm and 0.18 ± 0.27 cm in the 8th and 12th weeks, respectively was significantly less than that of the control group with the mean of 0.64 ± 0.78 cm and 0.56 ± 0.44, respectively (P < 0.05). Twelve weeks after the intervention, 84.1% of the lesions in the case group and 65.9% of the lesions in the control group were completely improved (P < 0.05). Conclusion: According to the results of the present study, the improvement of leishmaniasis lesion with the topical application of the combination of P. ovata and vinegar was significantly more than that of the control group in the 8th and 12th weeks after the intervention.

9.
Parasit Vectors ; 16(1): 72, 2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36797798

RESUMEN

BACKGROUND: Treatment of cutaneous leishmaniasis (CL) remains a major challenge for the public health and medical community. It has been claimed that natural compounds derived from fly larvae have anti-leishmania properties against some species of Leishmania. The present study aimed at assessing the in vitro effects of larval products of Lucilia sericata against the promastigote and intracellular amastigote forms of Leishmania major. Also, the therapeutic effect of larval products on lesions induced by L. major infection was evaluated in BALB/c mice models. METHODS: Parasite specimens and macrophage cells were exposed to varying concentrations of larval products for 24-120 h. Lesion progression and parasite load were investigated in the models to assess the therapeutic effects of the products. RESULTS: The larval products displayed more potent cytotoxicity against L. major promastigotes. The IC50 values for larval saliva and hemolymph were 100.6 and 37.96 ug/ml, respectively. The IC50 of glucantime was 9.480 ug/ml. Also, the saliva and hemolymph of L. sericata exhibited higher cytotoxicity against the promastigotes of L. major but were less toxic to the macrophage cells. Treatment with leishmanicidal agents derived from larvae of L. sericata decreased the infection rate and the number of amastigotes per infected host cell at all concentrations. Lesion size was significantly (F (7, 38) = 8.54, P < 0.0001) smaller in the treated mice compared with the untreated control group. The average parasite burden in the treated mice groups (1.81 ± 0.74, 1.03 ± 0.45 and 3.37 ± 0.41) was similar to the group treated with a daily injection of glucantime (1.77 ± 0.99) and significantly lower (F (7, 16) = 66.39, P < 0.0001) than in the untreated control group (6.72 ± 2.37). CONCLUSIONS: The results suggest that the larval products of L. sericata were effective against L. major parasites both in vivo and in vitro. However, more clinical trial studies are recommended to evaluate the effects of these larval products on human subjects.


Asunto(s)
Antiprotozoarios , Dípteros , Leishmania major , Leishmaniasis Cutánea , Humanos , Animales , Ratones , Larva , Antimoniato de Meglumina/uso terapéutico , Hemolinfa , Saliva , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/parasitología , Ratones Endogámicos BALB C , Antiprotozoarios/farmacología
10.
Iran J Parasitol ; 18(4): 419-426, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38169758

RESUMEN

Background: Cutaneous leishmaniasis (CL) is a parasitic disease that presents a broad spectrum of clinical features. Treatment of CL is problematic. We aimed to compare the field therapeutic efficacy of topical nanoliposomes containing 0.4% amphotericin B (Nano Lip-AmB) alone and in combination with cryotherapy and/or Glucantime® on human CL in the endemic areas of Iran. Methods: This retrospective study was performed based on the results of using Nano Lip-AmB alone or with Glucantime® and/or cryotherapy in the treatment of zoonotic cutaneous leishmaniasis (ZCL) in patients referred to health centers of Isfahan, Golestan and Ilam Provinces of Iran as endemic foci of ZCL caused by Leishmania major besides Mashhad and Bam cities as endemic foci of anthroponotic cutaneous leishmaniasis (ACL) caused by with L. tropica. Results: Two hundred and seventy-eight patients with CL were included in the current study. All of the patients (100%) who received Nano Lip-AmB alone or in combination with Glucantime® and/or cryotherapy based on guideline of Iranian national committee for the treatment of CL. Two patients with 7 skin lesions, who was resident in ACL endemic area and received Nano Lip-AmB plus Glucantime® and another patient was a resident of ZCL endemic area and received Nano Lip-AmB plus cryotherapy showed clinical relapses after treatment. Conclusion: Sina Ampholeish® in combination with other standard protocols of treatment of CL is well tolerated and with acceptable clinical efficacy rate.

11.
East Mediterr Health J ; 28(9): 658-663, 2022 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-36205204

RESUMEN

Background: Topical nanoliposomes containing 0.4% amphotericin B (Lip-AmB 0.4%) have shown promising safety results in preclinical and phase 1 clinical trials in healthy volunteers. Aims: To evaluate safety and efficacy of Lip-AmB 0.4% in cutaneous leishmaniasis patients. Methods: Fourteen patients with a total of 84 lesions received national standard treatment of weekly intralesional meglumine antimoniate with biweekly cryotherapy, or daily intramuscular meglumine antimoniate (20 mg/kg/day for 14 days), and topical Lip-AmB 0.4% twice daily for 28 days. Twenty-two patients with a total of 46 lesions (7 at most) were treated with topical Lip-AmB 0.4% alone twice daily for 28 days. Thirty patients with a total of 68 lesions received national standard treatment of weekly intralesional meglumine antimoniate (to blanch around the lesion) and biweekly cryotherapy. Results: Sixty-six patients with cutaneous leishmaniasis lesions completed the study. In the safety evaluation, 2 of the 36 patients evaluated reported a tolerable burning sensation and they preferred to continue treatment. Twelve (92%) of 14 patients with 84 lesions who received national standard treatment combined with Lip-AmB 0.4% completed the study with complete cure. In 1 of the patients with 4 lesions, 1 lesion showed complete cure and 3 showed partial cure. Among 22 patients with 46 lesions who received only topical LipAmB 0.4%, 19 completed the study and 18 showed complete cure (95% efficacy). In the 30 patients who received national standard treatment alone, 33 lesions in 15 patients showed complete cure (48.5%) on day 42 follow-up. Conclusion: Lip-AmB 0.4% alone or in combination with national standard treatment is safe with high-efficacy rate and warrants further investigation during phase 3 clinical trials.


Asunto(s)
Antiprotozoarios , Leishmania major , Leishmaniasis Cutánea , Compuestos Organometálicos , Adulto , Anfotericina B/efectos adversos , Antiprotozoarios/uso terapéutico , Femenino , Humanos , Irán , Leishmaniasis Cutánea/tratamiento farmacológico , Masculino , Meglumina/efectos adversos , Antimoniato de Meglumina/uso terapéutico , Persona de Mediana Edad , Compuestos Organometálicos/efectos adversos , Proyectos Piloto , Resultado del Tratamiento
13.
J Dermatolog Treat ; 33(3): 1418-1423, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-32972289

RESUMEN

BACKGROUND AND AIM: It is widely accepted that the high prevalence of leishmaniasis, demands the search for a tolerable effective treatment with the least side effects. This study aimed to evaluate the effect of treatment with clarithromycin on regression of lesions. MATERIALS AND METHODS: This study was performed on 20 patients with leishmaniasis referred to dermatology clinic in 2017-2018. They were divided into two groups of intervention (500 mg oral clarithromycin twice a day) and control (20 mg/kg/day systematic glucantime). Induration size of lesions was recorded. RESULTS: We had 20 patients with acute cutaneous leishmaniasis (CL) with 45 lesions in the control group and 49 lesions in the intervention group. In the control group, the mean number of lesions was 3 ± 2.8 and 5 ± 4.3 in each person in the control and intervention group (p=.63). The mean size of the largest diameter of lesions' induration at the beginning of the treatment was 19.81 ± 13 and 15.47 ± 15.6 mm in control and intervention group (p=.3) which changed to 1.59 and 0 respectively in three months after the treatment (p=.001). CONCLUSIONS: We concluded oral clarithromycin had therapeutic effects on acute CL similar to systematic glucantime and could be considered as a safe and effective treatment option.


Asunto(s)
Antiprotozoarios , Leishmaniasis Cutánea , Compuestos Organometálicos , Antiprotozoarios/uso terapéutico , Claritromicina/uso terapéutico , Humanos , Leishmaniasis Cutánea/tratamiento farmacológico , Meglumina/uso terapéutico , Antimoniato de Meglumina/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Resultado del Tratamiento
14.
Rev. biol. trop ; 69(4)dic. 2021.
Artículo en Inglés | LILACS, SaludCR | ID: biblio-1387696

RESUMEN

Abstract Introduction: Intralesional-pentavalent antimonials (IL-SbV) are recommended for simple cutaneous leishmaniasis (CL). Few treatment sessions (1-5) and drug volumes (1-5 ml each), relative to lesion size (LS), are recommended. There is not a validated IL-SbV protocol using doses calculated as mg/kg body weight and administered over a large number of IL-sessions, with small injection volumes. Objective: The study aim was to determine the efficacy of different concentrations of IL-SbV administered in 29 daily sessions of 100 μL each, on CL infected mice. Methods: Leishmania (Viannia) panamensis and L. (V.) braziliensis-infected mice (N = 6) were treated with 150, 50, and 16.6 mgSbV/kg/day x 29 days. Percentage of lesion area reduction, aesthetic and final (no lesions, no parasites) efficacy and effective dose (ED)50 were determined. In vitro-SbV activity against parasites was evaluated for both species. Results: The ED50 values were 72.2 and 66.3 (at the end of treatment), 54.3 and 37.7 (15-days pt.), and 145.3 and 148.6 (60-days pt.) for each species, respectively. Differences were observed between Leishmania species at 15-days pt., but not later. At 60-day pt., IL-SbV-150 mg showed final cure rates of 66.6 % for L. (V.) panamensis and 33.3 % for L. (V.) braziliensis-infected mice. After 15 days pt., lesion reactivation was observed in some "aesthetically cured" mice. Glucantime was not active in in vitro assays. Conclusions: The IL-SbV use with a dose calculated as mg/kg body weight and administered over a large number of IL-sessions, with small injection volumes each day could be effective against L. (V.) panamensis and L. (V.) braziliensis-CL infection. An appropriate SbV-dose (higher than 150 mg/kg/day x less than 29 days) must be evaluated.


Resumen Introducción: Los antimoniales pentavalentes aplicados intralesionalmente (IL-SbV) se recomiendan para el tratamiento de la leishmaniasis cutánea (LC) simple. Se recomiendan pocas sesiones (1-5) y volúmenes (1-5 ml cada uno) en relación con el tamaño de la lesión (LS). No existe un protocolo de IL-SbV validado que utilice dosis calculadas según el peso corporal (en mg/kg) y administradas durante varias sesiones en pocos volúmenes de inyección. Objetivo: El objetivo del estudio fue determinar la eficacia de diferentes concentraciones de IL-SbV administradas en 29 sesiones diarias de 100 μL cada una, en ratones con LC. Métodos: Ratones infectados con L. (V.) panamensis y L. (V.) braziliensis (N = 6) fueron tratados intralesionalmente con 150, 50 y 16,6 mg SbV/kg/día x 29 días. Se determinó el porcentaje de reducción del área de la lesión, la eficacia estética y final (sin lesiones, sin parásitos) y la dosis efectiva (DE)50. Adicionalmente de evaluó la actividad in vitro del SbV. Resultados: Los valores de DE50 fueron 72.2 y 66.3 (al final del tratamiento), 54.3 y 37.7 (15 días pt) y 145.3 y 148.6 (60 días pt) para cada especie. Se encontraron diferencias entre las especies sólo a los 15 días pt. La eficacia del tratamiento IL-SbV-150 mg, 60 días pt., fue de 66.6 y 33.3 % en ratones infectados con L. (V.) panamensis L. (V.) braziliensis respectivamente. Después de 15 días pt., se observó reactivación de la lesión en algunos ratones "estéticamente curados". Glucantime no fue activo in vitro. Conclusiones: El uso intralesional de SbV con una dosis calculada en mg/kg de peso corporal y administrada durante varias sesiones, con pequeños volúmenes de inyección cada día, podría ser eficaz en LC por L. (V.) panamensis y L. (V.) braziliensis. Dosis adecuadas de SbV (superiores a 150 mg/kg/día x 20) deben evaluarse.


Asunto(s)
Animales , Ratones , Antimoniato de Meglumina , Leishmania
15.
Macromol Biosci ; 21(7): e2100046, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34117834

RESUMEN

Leishmaniasis is a human and animal disease endemic in tropical and subtropical areas treated by means of pentavalent antimony as first-line approach. Unfortunately, the formulations available on the market are characterized by significant side effects and a total remission of the disease is difficult to be obtained. The aim of this investigation is to describe the development and characterization of aqueous-core poly-l-lactide (PLA) nanocapsules containing glucantime (meglumine antimoniate, MA) with the aim of increasing the pharmacological efficacy of the active compound. The polymeric systems characterized by a mean diameter of ≈300 nm exert a great interaction with murine macrophages. MA-loaded PLA nanocapsules show a great antileishmanial activity on mice infected with Leishmania infantum with respect to the free drug, favoring a decrease of the administration times. The biodistribution profiles demonstrate a lower renal accumulation of MA after its nanoencapsulation and a significant increase of its plasmatic half-life. The parasite load evaluated by immunohistochemistry shows a significant decrease in liver, spleen, and kidneys when mice are treated with MA-loaded PLA nanocapsules especially after 45 days. The obtained results demonstrate the potential application of MA-loaded PLA nanocapsules as novel nanomedicine for the treatment of leishmaniasis.


Asunto(s)
Leishmania infantum , Nanocápsulas , Compuestos Organometálicos , Animales , Meglumina/química , Meglumina/farmacología , Meglumina/uso terapéutico , Antimoniato de Meglumina/farmacología , Ratones , Ratones Endogámicos BALB C , Compuestos Organometálicos/química , Poliésteres/farmacología , Distribución Tisular
16.
Front Cell Infect Microbiol ; 11: 615814, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33718267

RESUMEN

Treatment of leishmaniasis is a challenging subject. Although available, chemotherapy is limited, presenting toxicity and adverse effects. New drugs with antileishmanial activity are being investigated, such as antiparasitic compounds derived from plants. In this work, we investigated the antileishmanial activity of the biflavonoid amentoflavone on the protozoan Leishmania amazonensis. Although the antileishmanial activity of amentoflavone has already been reported in vitro, the mechanisms involved in the parasite death, as well as its action in vivo, remain unknown. Amentoflavone demonstrated activity on intracellular amastigotes in macrophages obtained from BALB/c mice (IC50 2.3 ± 0.93 µM). No cytotoxicity was observed and the selectivity index was estimated as greater than 10. Using BALB/c mice infected with L. amazonensis we verified the effect of an intralesional treatment with amentoflavone (0.05 mg/kg/dose, in a total of 5 doses every 4 days). Parasite quantification demonstrated that amentoflavone reduced the parasite load in treated footpads (46.3% reduction by limiting dilution assay and 56.5% reduction by Real Time Polymerase Chain Reaction). Amentoflavone decreased the nitric oxide production in peritoneal macrophages obtained from treated animals. The treatment also increased the expression of ferritin and decreased iNOS expression at the site of infection. Furthemore, it increased the production of ROS in peritoneal macrophages infected in vitro. The increase of ROS in vitro, associated with the reduction of NO and iNOS expression in vivo, points to the antioxidant/prooxidant potential of amentoflavone, which may play an important role in the balance between inflammatory and anti-inflammatory patterns at the infection site. Taken together these results suggest that amentoflavone has the potential to be used in the treatment of cutaneous leishmaniasis, working as an ally in the control and development of the lesion.


Asunto(s)
Biflavonoides , Leishmania , Leishmaniasis Cutánea , Leishmaniasis , Animales , Antioxidantes , Biflavonoides/farmacología , Leishmaniasis Cutánea/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C , Especies Reactivas de Oxígeno
17.
J Liposome Res ; 31(2): 169-176, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32228210

RESUMEN

Leishmaniasis is a parasitic disease treatable and curable, however, the chemotherapeutic agents for their treatment are limited. In South American countries, pentavalent antimonials are still the first line of treatment for cutaneous leishmaniasis with an efficacy of about 75%, but the toxicity of the drug causes serious side effects and remains as the main obstacle for treatment. New knowledge aimed to improve drug delivery into the intracellular environment is essential, especially for drugs currently used in the clinic, to develop new anti-Leishmania formulations. In the present study, we analysed the scientific literature to highlight the progress achieved in the last decade regarding the use of nanotechnology for improving the current leishmaniasis treatments. Results allowed us to conclude that the encapsulated Glucantime liposomal formulation can be improved by means of nanoparticle functionalization processes, resulting in new drug delivery systems that can be potentially proposed as alternative therapies for leishmaniasis treatment.


Asunto(s)
Antiprotozoarios , Leishmaniasis Cutánea , Leishmaniasis , Nanopartículas , Antiprotozoarios/uso terapéutico , Sistemas de Liberación de Medicamentos , Humanos , Leishmaniasis/tratamiento farmacológico , Leishmaniasis Cutánea/tratamiento farmacológico , Liposomas/uso terapéutico
19.
Parasitology ; 148(3): 361-365, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33190654

RESUMEN

There are available data on in vivo studies of monotherapy of zoonotic cutaneous leishmaniasis with some antibacterial drugs (doxycycline) and their comparison with meglumine antimoniate (glucantime). We used golden Syrian hamsters as a laboratory model. Experimental groups were formed, each of which was treated with one of the tested drugs. Infection of animals was carried out with Leishmania major promastigotes. We selected highly virulent strains of L. major culture isolated from human ulcers or rodents. Meglumine antimoniate monotherapy and doxycycline monotherapy are quite effective and do not differ by the 30th day of their use in such indicators as the average degree of local damage and the average number of Leishmania in the lesions. The main differences were recorded in terms of average body weight gain and average clinical recovery in favour of doxycycline. Leishmania in the lesion on the 60th day were completely absent in treatment with doxycycline. The experiment proved the effectiveness of doxycycline monotherapy: Leishmania in the lesions were absolutely absent by the end of the treatment.


Asunto(s)
Antiprotozoarios/farmacología , Doxiciclina/farmacología , Leishmaniasis Cutánea/tratamiento farmacológico , Zoonosis/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Mesocricetus
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