An open-label pharmacokinetics (PK) clinical trial was conducted to comparatively assess the PK and explore pharmacodynamics (PD) of miltefosine in children adults with cutaneous leishmaniasis (CL) Colombia. Sixty patients, 30 aged 2 12 years 18 60 years, were enrolled. Participants received (Impavido) at a nominal dose 2.5 mg/kg/day for 28 days. Miltefosine concentrations measured plasma peripheral blood mononuclear cells by liquid chromatography-tandem mass spectrometry samples obtained...

American cutaneous leishmaniasis (ACL) has been characterized as a zoonotic disease. However, peridomestic and domestic transmission have recorded in at least nine countries Central South America. The present study was undertaken to identify the etiologic agent of epidemic ACL Department Tolima, Colombia. Leishmania isolates were obtained during diagnosis 56 patients with who consulted local control program three municipalities Tolima. Species identified using monoclonal antibodies isoenzyme...

Background The inflammatory response is prominent in the pathogenesis of dermal leishmaniasis. We hypothesized that regulatory T cells (Tregs) may be diminished chronic leishmaniasis (CDL) and contribute to healing during treatment. Methodology/Principal Findings frequency functional capacity Tregs were evaluated at diagnosis following treatment CDL patients having lesions ≥6 months duration asymptomatically infected residents endemic foci. CD4+CD25hi expressing Foxp3 or GITR lacking...

ABSTRACT Chronic tegumentary leishmaniasis is characterized by a scarcity of parasites in lesions and heightened inflammatory response. Deregulated hyperactive inflammation contributes to tissue damage parasite persistence. The mechanisms which immune cells are recruited the lesion their relationship clinical outcomes remain elusive. We examined expression levels chemokines receptors relation outcome dermal caused Leishmania (Viannia) panamensis . Primary macrophages from healthy donors were...

Treatment failure is multifactorial. Despite the importance of host cell drug transporters and metabolizing enzymes in accumulation, distribution metabolism drugs targeting intracellular pathogens, their impact on efficacy antileishmanials unknown. We examined contribution pharmacologically relevant determinants human macrophages antimony-mediated killing Leishmania panamensis its relationship with outcome treatment meglumine antimoniate.Patients cutaneous leishmaniasis who failed (n = 8) or...

The immune mechanisms that contribute to the efficacy of treatment cutaneous leishmaniasis (CL) are not fully understood. aim this study was define correlates outcome CL caused by Leishmania (Viannia) species during standard care with pentavalent antimonials. We conducted a comparative expression profiling response genes in peripheral blood mononuclear cells (PBMCs) and lesion biopsy specimens obtained from patients before at end (EoT) meglumine antimoniate. ex vivo PBMCs L (V) panamensis...

Within its mammalian host, Leishmania resides and replicates as an intracellular parasite. The direct activity of antileishmanials must therefore depend on drug transport, metabolism, accumulation within the host cell. In this study, we explored role human macrophage transporters in antileishmanial miltefosine (MLF), only oral available for treatment visceral cutaneous leishmaniasis (CL). Membrane transporter gene expression primary macrophages infected vitro with Viannia panamensis exposed...

Control of cutaneous leishmaniasis (CL) relies on chemotherapy, yet gaps in our understanding the determinants therapeutic outcome impede optimization antileishmanial drug regimens. Pharmacodynamic (PD) parameters antimicrobials are based relationship between concentrations/exposure and microbial kill. However, viable Leishmania persist a high proportion individuals despite clinical resolution, indicating that other than parasite clearance involved efficacy.In this study, profiles expression...

Localized skin lesions are characteristic of cutaneous leishmaniasis (CL); however, Leishmania (Viannia) species, which responsible for most CL cases in the Americas, can spread systemically, sometimes resulting mucosal disease. Detection has been documented healthy tissues (conjunctiva, tonsils, and nasal mucosa) patients individuals with asymptomatic infection areas endemicity L (V) panamensis braziliensis transmission. However, conditions mechanisms that favor parasite persistence...

Early host-pathogen interactions drive the host response and shape outcome of natural infections caused by intracellular microorganisms. These involve a number immune non-immune cells tissues, along with an assortment pathogen-derived molecules. Our current knowledge has been predominantly derived from research on relationships between pathogens invaded cell(s), limiting our understanding how microbes elicit modulate immunological responses at organismal level. In this study, we explored...

Addition of the immunomodulator pentoxifylline (PTX) to antimonial treatment mucosal leishmaniasis has shown increased efficacy. This randomized, double-blind, placebo-controlled trial evaluated whether addition meglumine antimoniate (MA) improves therapeutic response in cutaneous (CL) patients. Seventy-three patients aged 18–65 years, having multiple lesions or a single lesion ≥ 3 cm were randomized receive: intramuscular MA (20 mg/kg/day × 20 days) plus oral PTX 400 mg thrice daily...

<ns4:p><ns4:bold>Background: </ns4:bold>Obtaining high quality RNA from skin biopsies is complex due the physical composition and content of nucleases this tissue. This becomes particularly challenging when using compromised samples with necrotic, inflammed or damaged areas, such as those patients suffering conditions, which affect more than 900 million people annually. We evaluated impact biopsy size tissue preservation method on quantity extracts.</ns4:p><ns4:p>...

Background: A high-throughput method using inductively coupled plasma mass spectrometry (ICP-MS) was developed and validated for the quantitative analysis of antimony in human peripheral blood mononuclear cells from patients with cutaneous leishmaniasis undergoing treatment meglumine antimoniate. Materials & methods: Antimony digested clinical samples 1% tetramethylammonium hydroxide/1% EDTA indium used as internal standard. Accuracy, precision stability were evaluated. Conclusion: Taking...

En el año 2020 surgió, de manera nunca antes vista, una infección viral respiratoria que ahora conocemos como por SARS-CoV-2 (COVID-19), caracterizada ser nueva aparición, muy transmisible y con mortalidad significativa (REF Metro Ciencia), lo desencadenó ola angustia desesperación para la sociedad, determinó, estrategia prevención contagios muerte, confinamiento obligatorio domiciliario, suspensión clases jornadas laborables. Ecuador es primera vez, fue en otros países del mundo, se...

<ns4:p><ns4:bold>Background: </ns4:bold>Obtaining high quality RNA from skin biopsies is complex due the physical composition and content of nucleases this tissue. This becomes particularly challenging when using compromised samples with necrotic, inflammed or damaged areas, such as those patients suffering conditions, which affect more than 900 million people annually. We evaluated impact biopsy size tissue preservation method on quantity extracts.</ns4:p><ns4:p>...

Los eventos iniciales en la infección por Leishmania spp.contribuyen al desenlace clínico.Los estudios de el modelo ratón muestran que parásito modula expresión quimiocinas y las vías señalización células producen.El objetivo este trabajo fue determinar si panamensis patrones leucocitos humanos.Materiales métodos.Se infectaron totales sangre periférica donantes sanos (n=3) pacientes con leishmaniasis in vitro 2 24 horas L. panamensis.Se examinó PCR-arrays se confirmó qRT-PCR.El nivel...

ABSTRACT Aim A high-throughput method using inductively coupled plasma mass spectrometry (ICP-MS) was developed and validated for the quantitative analysis of antimony in human peripheral blood mononuclear cells (PBMCs) from patients with cutaneous leishmaniasis undergoing treatment meglumine antimoniate. Methods For this study, digested clinical samples 1% TMAH / EDTA indium used as internal standard. Calibration curves antimony, over range 25 to 10000 ng/mL were fitted a linear model...