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1.
Front Pharmacol ; 13: 929493, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910377

RESUMO

Leishmaniasis are a group of diseases caused by parasitic protozoa of the genus Leishmania. Current treatments are limited by difficult administration, high cost, poor efficacy, toxicity, and growing resistance. New agents, with new mechanisms of action, are urgently needed to treat the disease. Although extensively studied in other organisms, serine proteases (SPs) have not been widely explored as antileishmanial drug targets. Herein, we report for the first time an activity-based protein profiling (ABPP) strategy to investigate new therapeutic targets within the SPs of the Leishmania parasites. Active-site directed fluorophosphonate probes (rhodamine and biotin-conjugated) were used for the detection and identification of active Leishmania serine hydrolases (SHs). Significant differences were observed in the SHs expression levels throughout the Leishmania life cycle and between different Leishmania species. Using iTRAQ-labelling-based quantitative proteomic mass spectrometry, we identified two targetable SPs in Leishmania mexicana: carboxypeptidase LmxM.18.0450 and prolyl oligopeptidase LmxM.36.6750. Druggability was ascertained by selective inhibition using the commercial serine protease inhibitors chymostatin, lactacystin and ZPP, which represent templates for future anti-leishmanial drug discovery programs. Collectively, the use of ABPP method complements existing genetic methods for target identification and validation in Leishmania.

3.
Muscle Nerve ; 59(5): 555-560, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30697788

RESUMO

INTRODUCTION: Short tau inversion recovery (STIR) sequences in whole-body MRI are usually used for detecting muscle edema (ME) in inflammatory myopathies. We evaluated b-value 800 diffusion-weighted imaging (b800 DWI). METHODS: Two radiologists independently and a consensus reader retrospectively reexamined 60 patients with inflammatory myopathies and 15 controls. For each participant, 78 muscles were analyzed with 3 sets of imaging acquisitions: T1-weighted (T1) turbo spin echo and STIR; T1 and DWI; and T1, STIR and DWI. Mean edema per patient was compared between sequences. Agreement was evaluated. RESULTS: Diffusion-weighted imaging detected more ME compared with STIR (P < 0.001). Agreement between readers was better with both sequences (k = 0.94) than with b800 DWI (k = 0.89) or STIR (k = 0.84) alone. DISCUSSION: Diffusion-weighted imaging is a valuable add-on for the study of inflammatory myopathies. Muscle Nerve 59:555-555, 2019.


Assuntos
Edema/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Miosite/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Creatina Quinase/sangue , Dermatomiosite/sangue , Dermatomiosite/diagnóstico por imagem , Dermatomiosite/patologia , Imagem de Difusão por Ressonância Magnética , Feminino , Frutose-Bifosfato Aldolase/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Miosite/sangue , Miosite/patologia , Miosite de Corpos de Inclusão/sangue , Miosite de Corpos de Inclusão/diagnóstico por imagem , Miosite de Corpos de Inclusão/patologia , Polimiosite/sangue , Polimiosite/diagnóstico por imagem , Polimiosite/patologia , Estudos Retrospectivos , Imagem Corporal Total , Adulto Jovem
4.
Mem Inst Oswaldo Cruz ; 108(2): 131-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23579789

RESUMO

The goal of this study was to demonstrate the usefulness of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of pulmonary tuberculosis (PTB) and extrapulmonary TB (EPTB). This assay used 20 amino acid-long, non-overlapped synthetic peptides that spanned the complete Mycobacterium tuberculosis ESAT-6 and Ag85A sequences. The validation cohort consisted of 1,102 individuals who were grouped into the following five diagnostic groups: 455 patients with PTB, 60 patients with EPTB, 40 individuals with non-EPTB, 33 individuals with leprosy and 514 healthy controls. For the PTB group, two ESAT-6 peptides (12033 and 12034) had the highest sensitivity levels of 96.9% and 96.2%, respectively, and an Ag85A-peptide (29878) was the most specific (97.4%) in the PTB groups. For the EPTB group, two Ag85A peptides (11005 and 11006) were observed to have a sensitivity of 98.3% and an Ag85A-peptide (29878) was also the most specific (96.4%). When combinations of peptides were used, such as 12033 and 12034 or 11005 and 11006, 99.5% and 100% sensitivities in the PTB and EPTB groups were observed, respectively. In conclusion, for a cohort that consists entirely of individuals from Venezuela, a multi-antigen immunoassay using highly sensitive ESAT-6 and Ag85A peptides alone and in combination could be used to more rapidly diagnose PTB and EPTB infection.


Assuntos
Antígenos de Bactérias , Mycobacterium tuberculosis/imunologia , Peptídeos , Tuberculose/diagnóstico , Adulto , Antígenos de Bactérias/imunologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/imunologia , Sensibilidade e Especificidade , Tuberculose/imunologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/imunologia
5.
Mem. Inst. Oswaldo Cruz ; 108(2): 131-139, abr. 2013. tab, graf
Artigo em Inglês | LILACS | ID: lil-670411

RESUMO

The goal of this study was to demonstrate the usefulness of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of pulmonary tuberculosis (PTB) and extrapulmonary TB (EPTB). This assay used 20 amino acid-long, non-overlapped synthetic peptides that spanned the complete Mycobacterium tuberculosis ESAT-6 and Ag85A sequences. The validation cohort consisted of 1,102 individuals who were grouped into the following five diagnostic groups: 455 patients with PTB, 60 patients with EPTB, 40 individuals with non-EPTB, 33 individuals with leprosy and 514 healthy controls. For the PTB group, two ESAT-6 peptides (12033 and 12034) had the highest sensitivity levels of 96.9% and 96.2%, respectively, and an Ag85A-peptide (29878) was the most specific (97.4%) in the PTB groups. For the EPTB group, two Ag85A peptides (11005 and 11006) were observed to have a sensitivity of 98.3% and an Ag85A-peptide (29878) was also the most specific (96.4%). When combinations of peptides were used, such as 12033 and 12034 or 11005 and 11006, 99.5% and 100% sensitivities in the PTB and EPTB groups were observed, respectively. In conclusion, for a cohort that consists entirely of individuals from Venezuela, a multi-antigen immunoassay using highly sensitive ESAT-6 and Ag85A peptides alone and in combination could be used to more rapidly diagnose PTB and EPTB infection.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos de Bactérias , Mycobacterium tuberculosis/imunologia , Peptídeos , Tuberculose/diagnóstico , Antígenos de Bactérias/imunologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Peptídeos/imunologia , Sensibilidade e Especificidade , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/imunologia , Tuberculose/imunologia
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