RESUMO
Malaria is a parasitic infectious disease caused by Plasmodium sp, which was responsible for about 409 thousand deaths only in 2019. The clinical manifestations in patients with malaria, which may include fever and anemia and that can occasionally lead to the death of the host, are mainly associated to the asexual blood stage of parasite. The discovery of novel compounds active against stages of the intraerythrocytic cell cycle has been the focus of many researches seeking for alternatives to the control of malaria. The antimalarial effect of a native cationic polypeptide from the venom of a South American rattlesnake named crotamine, with ability of targeting and disrupting the acidic compartments of Plasmodium falciparum parasite, was previously described by us. Herein, we extended our previous studies by investigating the internalization and trafficking of crotamine in P. falciparum-infected erythrocytes at different blood-stages of parasites and periods of incubation. In addition, the effects of several pharmacological inhibitors in the uptake of this snake polypeptide with cell-penetrating properties were also assessed, showing that crotamine internalization was dependent on ATP generated via glycolytic pathway. We show here that crotamine uptake is blocked by the glycolysis inhibitor 2-deoxy-D-glucose, and the most efficient internalization is observed at trophozoite stage of parasite after at least 30 min of incubation. The present data provide important insights into biochemical pathway and cellular features determined by the parasite cycle, which may be underlying the internalization and effects of cationic antimalarials as crotamine.
Assuntos
Venenos de Crotalídeos/química , Eritrócitos , Peptídeos , Plasmodium falciparum , Animais , Crotalus , Eritrócitos/efeitos dos fármacos , Eritrócitos/parasitologia , Humanos , Peptídeos/farmacologia , América do SulRESUMO
We show here that crotamine, a polypeptide from the South American rattlesnake venom with cell penetrating and selective anti-fungal and anti-tumoral properties, presents a potent anti-plasmodial activity in culture. Crotamine inhibits the development of the Plasmodium falciparum parasites in a dose-dependent manner [IC50 value of 1.87 µM], and confocal microscopy analysis showed a selective internalization of fluorescent-labeled crotamine into P. falciparum infected erythrocytes, with no detectable fluorescence in uninfected healthy erythrocytes. In addition, similarly to the crotamine cytotoxic effects, the mechanism underlying the anti-plasmodial activity may involve the disruption of parasite acidic compartments H(+) homeostasis. In fact, crotamine promoted a reduction of parasites organelle fluorescence loaded with the lysosomotropic fluorochrome acridine orange, in the same way as previously observed mammalian tumoral cells. Taken together, we show for the first time crotamine not only compromised the metabolism of the P. falciparum, but this toxin also inhibited the parasite growth. Therefore, we suggest this snake polypeptide as a promising lead molecule for the development of potential new molecules, namely peptidomimetics, with selectivity for infected erythrocytes and ability to inhibit the malaria infection by its natural affinity for acid vesicles.
Assuntos
Antimaláricos/farmacologia , Peptídeos Penetradores de Células/farmacologia , Venenos de Crotalídeos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Venenos de Serpentes/química , Laranja de Acridina/metabolismo , Sequência de Aminoácidos , Animais , Antimaláricos/isolamento & purificação , Transporte Biológico , Carbocianinas/química , Peptídeos Penetradores de Células/isolamento & purificação , Células Cultivadas , Cloroquina/farmacologia , Venenos de Crotalídeos/isolamento & purificação , Crotalus/metabolismo , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Eritrócitos/parasitologia , Corantes Fluorescentes/química , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Concentração Inibidora 50 , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/metabolismo , Coloração e Rotulagem , Vacúolos/efeitos dos fármacos , Vacúolos/parasitologiaRESUMO
BACKGROUND AND AIMS: Hypertriglyceridemia is an important independent risk factor for coronary artery diseases and is determined by a wide range of factors, both genetic and exogenous. The A5 apolipoprotein, which is associated with the synthesis and removal of triglycerides (TG), is encoded by the APOA5 gene. One of the polymorphisms of this gene that has been the focus of a large number of studies, and which appears to be associated with increased TG, is S19W (rs 3135506). In this study, we examined the influence of this single nucleotide polymorphism (SNP) on TG levels of a sample of southern Brazilians. METHODS AND RESULTS: Samples obtained from 567 people of European descent were genotyped; interactions between this variant and anthropometric variables were analyzed, and the effects of lifestyle, sex, menopause, and variations of the APOE gene were evaluated. We found that the 19W allele is associated with increased TG (p = 0.025) and that this influence was modulated by sex (p = 0.003), menopause (p = 0.022) and the presence of the E*4 allele (p = 0.027). CONCLUSION: Our data showed, for the first time, the importance and magnitude of the influence of the S19W variant in a southern Brazilian population.
Assuntos
Apolipoproteínas A/genética , Apolipoproteínas E/genética , Menopausa , Polimorfismo de Nucleotídeo Único , Triglicerídeos/sangue , Adulto , Alelos , Apolipoproteína A-V , Apolipoproteínas A/metabolismo , Apolipoproteínas E/metabolismo , Brasil , Doença da Artéria Coronariana , Feminino , Genótipo , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/genética , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
The Sinos River, in southern Brazil, is polluted by industrial discharges and untreated urban wastes. Fish genotoxicity biomarkers are valuable parameters for environmental risk assessment. In this study, we used the comet assay to detect genotoxicity due to multiple sources of pollution in the peripheral blood of a native fish species (Hyphessobrycon luetkenii). In addition, we analysed possible DNA damage from aluminum, lead, chromium, copper, nickel, iron and zinc contamination. Water samples were collected seasonally from three sampling sites and the fish were assessed under laboratory conditions. Water chemical analysis showed an increased level of aluminum and iron in most of the samples at sites 2 and 3, located in the middle and lower river course, respectively. The index of DNA damage assessed by the comet assay demonstrated no significant differences in different seasons or at the different sampling sites, while the frequency of cells with DNA damage was higher in water samples collected at sites 1 and 2 during the spring season. None of the metals studied seems to be associated with the increase in the frequency of cells with DNA damage observed during the spring season. The results of this study indicate that the Sinos River is contaminated with substances that are genotoxic to fish, including the waters near the river spring.
Assuntos
Dano ao DNA/efeitos dos fármacos , Monitoramento Ambiental , Peixes , Rios/química , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores , Brasil , Ensaio Cometa , Estações do Ano , Poluentes Químicos da Água/químicaRESUMO
OBJETIVOS: Este estudo teve como objetivo avaliar sintomas de dor, apertamento dos dentes, qualidade do sono e sensibilidade dolorosa nos principais músculos mastigatórios e estabilizadores cervicais e qualidade de vida de mulheres com Disfunção Temporomandibular (DTM). MÉTODOS: Foram avaliadas 45 mulheres, divididas em dois grupos. O grupo I, composto por 27 mulheres (30,1±5,8anos) com diagnóstico de DTM e o grupo II, controle, composto por 18 mulheres saudáveis (23,4±2,3 anos). A intensidade dos sintomas de dor, cefaleia, cervicalgia, de apertamento dos dentes e dificuldade de dormir foram avaliados por escala visual analógica (EVA), o limiar de dor dos músculos masseter, temporal anterior, trapézio superior e esternocleidomastoideo, com dolorímetro e a qualidade de vida, pelo SF-36. Foi realizada análise estatística e o nível de significância foi α=0,05. RESULTADOS: Os resultados mostram que mulheres com DTM têm sintomas mais intensos de cefaleia (p<0,001), cervicalgia (p<0,001), intensidade de apertamento dos dentes (p<0,001) e dificuldade de dormir (p<0,001). Também apresentam limiar de dor mais baixo nos músculos masseter (p<0,001), temporal anterior (p<0,001), trapézio superior (p<0,001), esternocleidomastoideo (p<0,001) e pior qualidade de vida em todos os domínios avaliados (p<0,05), quando comparados com o grupo controle. CONCLUSÕES: Mulheres com DTM têm maior intensidade dos sintomas de dor, apertamento dos dentes, dificuldade de dormir, maior sensibilidade dolorosa em músculos mastigatórios e cervicais e pior qualidade de vida quando comparadas com mulheres sem DTM.
OBJECTIVES: The aim of this study was to evaluate pain symptoms, teeth clenching, quality of sleep, sensitivity to pain in the main masticatory and stabilizer muscles, and quality of life among women with temporomandibular disorder (TMD). METHODS: Forty-five women were evaluated and divided into two groups. Group I included 27 women (mean age 30.1±5.8 years) with a diagnosis of TMD and Group II (control) included 18 healthy women (mean age 23.4±2.3 years). The intensity of pain symptoms (headache, neck pain), teeth clenching and trouble sleeping was evaluated using a visual analog scale (VAS). The pain thresholds of the masseter, anterior temporalis, upper trapezius and sternocleidomastoid muscles were evaluated using a dolorimeter. Quality of life was evaluated using SF-36. Statistical analysis was performed and the significance level was α<0.05. RESULTS: The results showed that the women with TMD presented more intense headache (p<0.001), neck pain (p<0.001), teeth clenching (p<0.001) and trouble sleeping (p<0.001). They also presented lower pain threshold in the masseter (p<0.001), anterior temporalis (p<0.001), upper trapezius (p<0.001) and sternocleidomastoid (p<0.001) muscles and lower quality of life in all evaluated domains (p<0.05) when compared with the control group. CONCLUSIONS:Women with TMD had greater intensity of pain symptoms, teeth clenching, trouble sleeping, sensitivity to pain in the masticatory and neck muscles and lower quality of life, compared with women without TMD.
RESUMO
Cytokinesis-block micronucleus (CB-MN) assay and single-cell gel electrophoresis (SCGE) were employed to analyze leukocytes from 14 Fanconi anemia (FA) patients, 30 Down syndrome (DS) patients, and 30 control individuals, to examine the sensitivity of these techniques to detect genomic instability in these 2 diseases. The DS patients presented increased DNA damage as measured by SCGE in relation to controls. The frequencies of micronuclei and dicentric bridges were similar to those of controls. Micronucleus frequency, dicentric bridge frequencies, and DNA damage were higher in FA patients than in controls. The high frequency of micronuclei observed in FA patients seems to be due to clastogenic events, because an increase in the frequency of dicentric bridges was also observed. Micronuclei are expressed mutations and need cell division to appear. The damage detected by SCGE is repairable, and does not require cell division. Under alkaline conditions, SCGE assesses double- and single-strand breaks and alkali-labile sites. The 2 methods are efficient for monitoring mutagenic events in exposed populations or in individuals with genetic instability. While the damage measured by micronucleus analysis is accumulated over a long period of time, DNA damage measured by SCGE reflects recent, unrepaired events.
Assuntos
Síndrome de Down/genética , Anemia de Fanconi/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Ensaio Cometa , Feminino , Humanos , Lactente , Masculino , Testes para Micronúcleos , Sensibilidade e EspecificidadeRESUMO
The mutagenic and carcinogenic effects of genotoxic agents on exposed people have constituted an increasing concern. Therefore, the objective of this work was to assess DNA damage in lymphocytes of workers exposed to X-radiation using the cytokinesis-blocked micronucleus test and the comet assay (single-cell gel electrophoresis), and to compare these two techniques in the monitoring of exposed populations. The cytokinesis-blocked micronucleus test and the comet assay were employed in the monitoring of 22 workers occupationally exposed to X-radiation in a hospital in southern Brazil. The frequency of dicentric bridges was also measured. The results of both assays and the frequency of dicentric bridges revealed a significant increase in genetic effects on the cells of exposed individuals. Age was significantly correlated with micronucleus frequency and damage index in the comet assay. The concomitant analysis of dicentric bridges when determining micronucleus frequency does not require much extra work, and may serve as a reference to the type of mutagenic effect (clastogenic or aneugenic). The combination of the alkaline comet assay with the cytokinesis-blocked micronucleus test appears to be very informative for the monitoring of populations chronically exposed to genotoxic agents.
Assuntos
Dano ao DNA/efeitos da radiação , Linfócitos/efeitos da radiação , Exposição Ocupacional , Monitoramento de Radiação/métodos , Raios X , Adulto , Fatores Etários , Ensaio Cometa , Feminino , Humanos , Linfócitos/fisiologia , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , FumarRESUMO
A follow-up study was carried out 4 years after an initial evaluation of the micronucleus frequency in 10 healthy individuals who had been occupationally exposed to antineoplastic drugs in a Brazilian hospital. Upon the first evaluation, these 10 exposed individuals were compared with 10 non-exposed individuals matched for age, sex and smoking habits; the results revealed that the frequency of micronucleated lymphocytes in individuals exposed to antineoplastic drugs was significantly higher (P=0.038) than in controls. The frequency of dicentric bridges was also increased, although not significantly (P=0.0545). After the first analysis, the workers handling antineoplastic drugs were advised to modify their work schedule to limit exposure, and the number of workers in the group was increased from 10 to 12 individuals. In the follow-up study, 12 individuals from the same work area were assessed. In addition to micronucleus frequency, alkaline single cell gel electrophoresis was also used to monitor genetic hazard. This exposed group was compared to 12 non-exposed workers from the same hospital, matched for age, sex and smoking habits. In the follow-up study, no statistical difference was found between exposed workers and controls in terms of micronucleus and dicentric bridge frequency with the Mann--Whitney U-test (P=0.129 and 0.373, respectively). However, the mean value of SCGE analysis was significantly higher in the exposed group than in the controls (P=0.0006). Although the micronucleus analysis seems to be less sensitive to assess DNA damage, it detects chromosome aberrations and not just repairable DNA breakage and alkali-labile sites. Combination of the alkaline single cell gel electrophoresis and cytokinesis blocked micronucleus assay appears to be commendable to monitor populations chronically exposed to genotoxic agents.
Assuntos
Antineoplásicos/efeitos adversos , Dano ao DNA/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Mutagênicos/efeitos adversos , Enfermeiras e Enfermeiros , Farmacêuticos , Adulto , Células Cultivadas , Ensaio Cometa , DNA/efeitos dos fármacos , Monitoramento Ambiental , Feminino , Seguimentos , Humanos , Masculino , Testes para Micronúcleos , Valores de ReferênciaRESUMO
The Associação dos Pais e Amigos dos Excepcionais (APAE) is an institution for mentally retarded patients located at Caxias do Sul in the south of Brazil. A genetic diagnostic survey of 202 individuals from this institution is presented. The patients had a male:female ratio of 1.3:1 and their ages varied from 1 month to 47 years with a mean of 5.5 years. Using personal and family data, careful clinical examination and laboratory investigation, the authors established a definitive diagnosis in 132 patients (65.34%). A constitutional disorder was present in 111 patients (54.95%). Down's syndrome patients represented 32.15%, while 1.98% had other chromosomal anomalies. In 25 patients (12.37%) a disorder of Mendelian inheritance was diagnosed. In 8 patients (3.96%) a multiple congenital anomalies/mental retardation (MCA/MR) syndrome was recorded. Eight patients (3.96%) had a central nervous system (CNS) malformation. An acquired condition was observed in 21 patients (10.39%), including pre- or post-natal infections. In the remaining 70 patients (34.65%) a conclusive diagnosis was not possible.
Assuntos
Institucionalização , Deficiência Intelectual/genética , Adolescente , Adulto , Brasil , Sistema Nervoso Central/anormalidades , Criança , Pré-Escolar , Aberrações Cromossômicas , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Infecções , Masculino , SíndromeRESUMO
INTRODUCTION: Epidemiological surveillance activities undertaken after the detection of an active trachoma case in the APAE-SP are described. MATERIAL AND METHOD: A total of 1,009 pupils, employees and household contacts had an eye examination. Treatment control was carried out at the institution 4 times at 45 day-intervals. RESULTS: The overall prevalence was of 5.9%, 5.1% being of follicular trachoma (TF), 0.3% of intense trachoma (TF/TI) and 0.5% of cicatricial trachoma (TS). At the first control exercise 45.5% of the trachoma cases had no signs of the disease and 40.0% underwent treatment. At the last control exercise 20% were found to have been cured with no vestigial scars. Non-attendance was of 38.2%. The distribution of secondary cases showed great dispersion, suggesting dissemination throughout Greater S. Paulo. DISCUSSION AND CONCLUSIONS: The trachoma control activities do not show satisfactory results, perhaps due to the prolonged duration of the treatment and follow-up. The development of strategies of clinical intervention should be implemented for better control of the disease.
Assuntos
Vigilância da População , Tracoma/epidemiologia , Adolescente , Adulto , Brasil , Criança , Pré-Escolar , Humanos , PrevalênciaRESUMO
Chromosome studies on 28 specimens collected in two Brazilian populations of the rodent species Deltamys kempi disclosed seven different karyotypes, due to two autosome centric fusions (2;3 and 9;15) in homozygous and heterozygous states, and a Y-autosome translocation present in all males. These results, plus those obtained previously in a population from Argentina and another from Brazil, show that this species has 44% of carriers of four autosome centric fusions, and each rearrangement is restricted to a distinct locality.
Assuntos
Arvicolinae/genética , Adaptação Biológica , Animais , Aberrações Cromossômicas , Feminino , Cariotipagem , Masculino , Translocação GenéticaRESUMO
The control situation of hanseniasis patients' contacts needs a deeper study which would show the reality in the public health centers and their consequence over the whole country. The increasing of the prevalence rate of the disease added to the bad social-economic conditions of the patients and contacts gave us subsidies to important studies to understand the present epidemiological picture. This research had the purpose of diagnosing the control situation of hanseniasis patients' contacts in a public health center which had, at the moment of this research (1983) 160 hanseniasis patients (incidence of 1.2/1000) and 757 contacts registered in a Subprogram of Hansen's Disease Control.
Assuntos
Hanseníase/prevenção & controle , Programas Médicos Regionais , Adolescente , Adulto , Idoso , Brasil , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Hanseníase/transmissão , Hanseníase Dimorfa/prevenção & controle , Hanseníase Tuberculoide/prevenção & controle , Pessoa de Meia-IdadeRESUMO
In Hansen's disease, the third part of advanced incidences or non treated cases exhibit some patterns of physical incapacity, besides the prejudice and beliefs generated by deformities-which the patients may present if they do not get a correct treatment. Which basis on this problematical question of the disease a group of professionals composed of medical doctors, nurses, physical therapist, occupational therapist and social worker made a study of the incapacities of the Hansen's disease patients through a detailed physical exam. This study intended to identify sensory and motor injuries of the face, upper and lower limbs. This study also develops a research about the necessity to systematize the assistance given in a public health center.