Prevalence of self-medication and associated factors in adolescents aged 18-19 years: the 1997/1998 cohort in São Luís-MA, Brazil / Prevalência de automedicação e fatores associados em adolescentes de 18-19 anos: a coorte de 1997/1998 em São Luís-MA, Brasil

Abstract This article aims to assess the prevalence and factors associated with self-medication in adolescents. Cross-sectional study, nested in cohort, with 2,515 adolescents aged 18-19 years born in São Luís-MA. The use of medication in the last 15 days without a medical prescription or by a qualified professional was considered self-medication. Factors associated with self-medication were evaluated using Poisson regression with robust variances and hierarchical selection of variables. Medicines were used in the last 15 days by 48.05% of adolescents. Among these, 70.09% use it without a prescription or indication from another health professional. The most used medications for self-medication were "over the counter" (93.68%). Self-medication was positively associated with female gender (PR: 1.41; 95%CI: 1.25-1.59), screen time ≥5h/day (PR: 1.32; 95%CI: 1.05-1.67) and self-reported diagnosis of allergic rhinitis (PR: 1.19; 95%CI: 1.02-1.39); however, negatively associated with self-satisfaction with health (PR: 0.79; 95%CI: 0.67-0.94) and hospitalization in the previous year (PR: 0.70; 95%CI: 0.50-0.97). Self-medication was common among adolescents and to reduce this practice, greater attention should be given to women, individuals with intense exposure to meshes and allergic diseases.

Resumo O objetivo deste artigo é avaliar a prevalência e os fatores associados a automedicação em adolescentes. Estudo transversal, aninhado a uma coorte, com 2.515 adolescentes de 18-19 anos nascidos em São Luís-MA. O uso de algum medicamento nos últimos 15 dias sem prescrição médica ou de profissional habilitado foi considerado automedicação. Os fatores associados a automedicação foram avaliados usando regressão de Poisson com variâncias robustas e seleção hierárquica das variáveis. Medicamentos foram utilizados nos últimos 15 dias por 48,05% dos adolescentes. Entre estes, 70,09% fazem uso sem receita médica ou indicação de outro profissional de saúde. Os medicamentos mais utilizados na automedicação foram os "over the counter" (93,68%). A automedicação foi positivamente associada ao sexo feminino (RP: 1,41; IC95%: 1,25-1,59), tempo de tela ≥5h/dia (RP: 1,32; IC95%: 1,05-1,67) e diagnóstico autorreferido de rinite alérgica (RP: 1,19; IC95%: 1,02-1,39); porém, negativamente associada a autossatisfação com a saúde (PR: 0,79; IC95%: 0,67-0,94) e hospitalização no ano anterior (RP: 0,70; IC95%: 0,50-0,97). A automedicação foi comum entre os adolescentes e para redução dessa prática uma maior atenção deve ser dada a mulheres, indivíduos com intensa exposição a telas e doenças alérgicas.

Prevalence of self-medication and associated factors in adolescents aged 18-19 years: the 1997/1998 cohort in São Luís-MA, Brazil.

This article aims to assess the prevalence and factors associated with self-medication in adolescents. Cross-sectional study, nested in cohort, with 2,515 adolescents aged 18-19 years born in São Luís-MA. The use of medication in the last 15 days without a medical prescription or by a qualified professional was considered self-medication. Factors associated with self-medication were evaluated using Poisson regression with robust variances and hierarchical selection of variables. Medicines were used in the last 15 days by 48.05% of adolescents. Among these, 70.09% use it without a prescription or indication from another health professional. The most used medications for self-medication were "over the counter" (93.68%). Self-medication was positively associated with female gender (PR: 1.41; 95%CI: 1.25-1.59), screen time ≥5h/day (PR: 1.32; 95%CI: 1.05-1.67) and self-reported diagnosis of allergic rhinitis (PR: 1.19; 95%CI: 1.02-1.39); however, negatively associated with self-satisfaction with health (PR: 0.79; 95%CI: 0.67-0.94) and hospitalization in the previous year (PR: 0.70; 95%CI: 0.50-0.97). Self-medication was common among adolescents and to reduce this practice, greater attention should be given to women, individuals with intense exposure to meshes and allergic diseases.

Isobenzofuranone derivative JVPH3, an inhibitor of L. donovani topoisomerase II, disrupts mitochondrial architecture in trypanosomatid parasites.

Kinetoplast DNA (kDNA) bearing unusual mitochondrion of trypanosomatid parasites offers a new paradigm in chemotherapy modality. Topoisomerase II of Leishmania donovani (LdTopII), a key enzyme associated with kDNA replication, is emerging as a potential drug target. However, mode of action of LdTopII targeted compounds in the parasites at sub-cellular level remains largely unknown. Previously, we reported that an isobenzofuranone derivative, namely 3,5-bis(4-chlorophenyl)-7-hydroxyisobenzofuran-1(3H)-one (JVPH3), targets LdTopII and induces apoptosis-like cell death in L. donovani. Here, we elucidate the phenotypic changes and the events occurring at sub-cellular level caused by JVPH3 in L. donovani. In addition, we have evaluated the cytotoxicity and ultrastructural alterations caused by JVPH3 in two brazilian trypanosomatid pathogens viz. L. amazonensis and Trypanosoma cruzi. Despite killing these parasites, JVPH3 caused significantly different phenotypes in L. donovani and L. amazonensis. More than 90% population of parasites showed altered morphology. Mitochondrion was a major target organelle subsequently causing kinetoplast network disorganization in Leishmania. Altered mitochondrial architecture was evident in 75-80% Leishmania population being investigated. Quantification of mitochondrial function using JC-1 fluorophore to measure a possible mitochondrial membrane depolarization further confirmed the mitochondrion as an essential target of the JVPH3 corroborating with the phenotype observed by electron microscopy. However, the impact of JVPH3 was lesser on T. cruzi than Leishmania. The molecule caused mitochondrial alteration in 40% population of the epimastigotes being investigated. To our knowledge, this is the first report to evaluate the proliferation pattern and ultrastructural alterations caused in Brazilian kinetoplastid pathogens by a synthetic LdTopII inhibitor previously established to have promising in vivo activity against Indian strain of L. donovani.

KH-TFMDI, a novel sirtuin inhibitor, alters the cytoskeleton and mitochondrial metabolism promoting cell death in Leishmania amazonensis.

Treatment of leishmaniasis involves the use of antimonials, miltefosine, amphotericin B or pentamidine. However, the side effects of these drugs and the reports of drug-resistant parasites demonstrate the need for new treatments that are safer and more efficacious. Histone deacetylase inhibitors are a new class of compounds with potential to treat leishmaniasis. Herein, we evaluated the effects of KH-TFMDI, a novel histone deacetylase inhibitor, on Leishmania amazonensis promastigotes and intracellular amastigotes. The IC50 values of this compound for promastigotes and intracellular amastigotes were 1.976 and 1.148 µM, respectively, after 72 h of treatment. Microscopic analyses revealed that promastigotes became elongated and thinner in response to KH-TFMDI, indicating changes in cytoskeleton organization. Immunofluorescence microscopy, western blotting and flow cytometry using an anti-acetylated tubulin antibody revealed an increase in the expression of acetylated tubulin. Furthermore, transmission electron microscopy revealed several ultrastructural changes, such as (a) mitochondrial swelling, followed by the formation of many vesicles inside the matrix; (b) presence of lipid bodies randomly distributed through the cytoplasm; (c) abnormal chromatin condensation; and (d) formation of blebs on the plasma membrane. Physiological studies for mitochondrial function, flow cytometry with propidium iodide and TUNEL assay confirmed the alterations in the mitochondrial metabolism, cell cycle, and DNA fragmentation, respectively, which could result to cell death by mechanisms related to apoptosis-like. All these together indicate that histone deacetylases are promising targets for the development of new drugs to treat Leishmania, and KH-TFMDI is a promising drug candidate that should be tested in vivo.

Voacamine alters Leishmania ultrastructure and kills parasite by poisoning unusual bi-subunit topoisomerase IB.

Indole alkaloids possess a large spectrum of biological activities including anti-protozoal action. Here we report for the first time that voacamine, isolated from the plant Tabernaemontana coronaria, is an antiprotozoal agent effective against a large array of trypanosomatid parasites including Indian strain of Leishmania donovani and Brazilian strains of Leishmania amazonensis and Trypanosoma cruzi. It inhibits the relaxation activity of topoisomerase IB of L. donovani (LdTop1B) and stabilizes the cleavable complex. Voacamine is probably the first LdTop1B-specific poison to act uncompetitively. It has no impact on human topoisomerase I and II up to 200µM concentrations. The study also provides a thorough insight into ultrastructural alterations induced in three kinetoplastid parasites by a specific inhibitor of LdTop1B. Voacamine is also effective against intracellular amastigotes of different drug unresponsive field isolates of Leishmania donovani obtained from endemic zones of India severely affected with visceral leishmaniasis. Most importantly, this is the first report demonstrating the efficacy of a compound to reduce the burden of drug resistant parasites, unresponsive to SAG, amphotericin B and miltefosine, in experimental BALB/c mice model of visceral leishmaniasis. The findings cumulatively provide a strong evidence that voacamine can be a promising drug candidate against trypanosomatid infections.

Biology of human pathogenic trypanosomatids: epidemiology, lifecycle and ultrastructure.

Leishmania and Trypanosoma belong to the Trypanosomatidae family and cause important human infections such as leishmaniasis, Chagas disease, and sleeping sickness. Leishmaniasis, caused by protozoa belonging to Leishmania, affects about 12 million people worldwide and can present different clinical manifestations, i.e., visceral leishmaniasis (VL), cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), diffuse cutaneous leishmaniasis (DCL), and post-kala-azar dermal leishmaniasis (PKDL). Chagas disease, also known as American trypanosomiasis, is caused by Trypanosoma cruzi and is mainly prevalent in Latin America but is increasingly occurring in the United States, Canada, and Europe. Sleeping sickness or human African trypanosomiasis (HAT), caused by two sub-species of Trypanosoma brucei (i.e., T. b. rhodesiense and T. b. gambiense), occurs only in sub-Saharan Africa countries. These pathogenic trypanosomatids alternate between invertebrate and vertebrate hosts throughout their lifecycles, and different developmental stages can live inside the host cells and circulate in the bloodstream or in the insect gut. Trypanosomatids have a classical eukaryotic ultrastructural organization with some of the same main organelles found in mammalian host cells, while also containing special structures and organelles that are absent in other eukaryotic organisms. For example, the mitochondrion is ramified and contains a region known as the kinetoplast, which houses the mitochondrial DNA. Also, the glycosomes are specialized peroxisomes containing glycolytic pathway enzymes. Moreover, a layer of subpellicular microtubules confers mechanic rigidity to the cell. Some of these structures have been investigated to determine their function and identify potential enzymes and metabolic pathways that may constitute targets for new chemotherapeutic drugs.

A novel alkyl phosphocholine-dinitroaniline hybrid molecule exhibits biological activity in vitro against Leishmania amazonensis.

Parasitic protozoa of the Leishmania genus cause leishmaniasis, an important complex of tropical diseases that affect about 12 million people around the world. The drugs used to treat leishmaniasis are pentavalent antimonials, miltefosine, amphotericin B and pentamidine. In the present study, we evaluated the effect of a novel alkyl phosphocholine-dinitroaniline hybrid molecule, TC95, against Leishmania amazonensis promastigotes and intracellular amastigotes. Antiproliferative assays indicated that TC95 is a potent inhibitor of promastigotes and intracellular amastigotes with IC50 values of 2.6 and 1.2 µM, respectively. Fluorescence microscopy with anti-α-tubulin antibody revealed changes in the cytoskeleton, whilst scanning electron microscopy showed alterations in the shape, plasma membrane, length of the flagellum, and cell cycle. Flow cytometry confirmed the cell cycle arrest mainly in G1 phase, however a significant population appeared in sub G0/G1 and super-G2. The alterations in the plasma membrane integrity were confirmed by fluorometric analysis using Sytox Blue. Transmission electron microscopy also revealed an accumulation of lipid bodies, confirmed by fluorescence microscopy and fluorometric analysis using Nile Red. Important lesions were also observed in organelles such as mitochondrion, endoplasmic reticulum and Golgi complex. In summary, our study suggests that TC95, an alkyl phosphocholine-trifluralin hybrid molecule, is a promising novel compound against L. amazonensis.

Efficacy of miltefosine treatment in Leishmania amazonensis-infected BALB/c mice.

Leishmaniasis is one of the most serious worldwide diseases caused by protozoan parasites of the Leishmania genus, affecting millions of people around the world. All currently available treatments present severe toxic side effects, require long-term compliance, cause serious side effects and are uncomfortable for patients. Leishmania amazonensis, a species endemic to Brazil, causes severe localised or diffuse skin lesions in humans. Owing to the unsatisfactory nature of the currently available chemotherapies, new approaches have been assessed for improved therapeutic intervention strategies against leishmaniasis. Miltefosine is an alkylphospholipid analogue that exhibits potent activity against the different clinical manifestations of leishmaniasis. Thus, the aim of this study was to investigate the long-term efficacy of miltefosine in BALB/c mice infected with L. amazonensis owing to the lack of a profound study demonstrating its dose-dependent and long-term effects. It was observed that animals treated with 20-50 mg/kg/day of miltefosine exhibited a significant dose-dependent reduction in lesion size; furthermore, in mice receiving higher doses, lesions disappeared after the end of treatment. To confirm a possible parasitological cure, mice up to 250 days after the end of treatment were analysed. No lesions or presence of parasite DNA were found in mice treated with 30, 40 and 50 mg/kg/day of miltefosine. In summary, these results show that miltefosine may be used to treat cutaneous leishmaniasis caused by L. amazonensis, alone or as combination therapy.