RESUMO
Trichomoniasis, a prevalent sexually transmitted infection (STI) caused by the protozoan Trichomonas vaginalis, has gained increased significance globally. Its relevance has grown in recent years due to its association with a heightened risk of acquiring and transmitting the human immunodeficiency virus (HIV) and other STIs. In addition, many publications have revealed a potential link between trichomoniasis and certain cancers. Metronidazole (MTZ), a nitroimidazole compound developed over 50 years ago, remains the first-choice drug for treatment. However, reports of genotoxicity and side effects underscore the necessity for new compounds to address this pressing global health concern. In this study, we synthesized ten pyrazole-nitroimidazoles 1(a-j) and 4-nitro-1-(hydroxyethyl)-1H-imidazole 2, an analog of metronidazole (MTZ), and assessed their trichomonacidal and cytotoxic effects. All compounds 1(a-j) and 2 exhibited IC50 values ≤ 20 µM and ≤ 41 µM, after 24 h and 48 h, respectively. Compounds 1d (IC50 5.3 µM), 1e (IC50 4.8 µM), and 1i (IC50 5.2 µM) exhibited potencies equivalent to MTZ (IC50 4.9 µM), the reference drug, after 24 h. Notably, compound 1i showed high anti-trichomonas activity after 24 h (IC50 5.2 µM) and 48 h (IC50 2.1 µM). Additionally, all compounds demonstrated either non-cytotoxic to HeLa cells (CC50 > 100 µM) or low cytotoxicity (CC50 between 69 and 100 µM). These findings suggest that pyrazole-nitroimidazole derivatives represent a promising heterocyclic system, serving as a potential lead for further optimization in trichomoniasis chemotherapy.
Assuntos
Antiprotozoários , Nitroimidazóis , Tricomoníase , Trichomonas vaginalis , Humanos , Nitroimidazóis/farmacologia , Metronidazol/farmacologia , Células HeLa , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Tricomoníase/tratamento farmacológico , Pirazóis/farmacologia , Pirazóis/uso terapêuticoRESUMO
Giardiasis, caused by the protozoan Giardia intestinalis, affects around 400 million people worldwide, emphasizing the critical need for accurate diagnosis to enhance human health, especially in children. Prolonged giardiasis in childhood can lead to intellectual deficits and other complications. A variety of diagnostic tools, including microscopic, immunological, and molecular methods, are available for detecting G. intestinalis infection. Choosing the most suitable method can be challenging due to the abundance of options. This systematic review assesses the reliability and applicability of these diagnostic modalities. Utilizing the Dimensions and Wordart platforms for data analysis, we focus on relevant literature addressing diagnostic methods for human giardiasis. Microscopic techniques, particularly Ritchie's method, emerge as the primary choice, followed by enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). PCR's limited use is attributed to its high cost and infrastructure challenges in developing nations. In conclusion, our analysis supports microscopic methods as the gold standard for giardiasis diagnosis. However, in cases where symptoms persist despite a negative diagnosis, employing more sensitive diagnostic approaches is advisable.
RESUMO
Visceral leishmaniasis (VL) is a chronic systemic disease. In Brazil this infection is caused by Leishmania (Leishmania) infantum. Extracellular vesicles (EVs) released by Leishmania species have different functions like the modulation of host immune systems and inflammatory responses, among others. This study evaluated the participation of EVs from L. (L.) infantum (Leish-EVs) in recognition of the humoral and cellular immune response of hosts with VL. Promastigotes were cultivated in 199 medium and, in the log phase of growth, they were centrifuged, washed, resus-pended in RPMI medium, and incubated for 2 to 24 h, at 25 °C or 37 °C to release Leish-EVs. This dynamic was evaluated using transmission (TEM) and scanning (SEM) electron microscopies, as well as nanoparticle tracking analysis (NTA). The results suggested that parasite penetration in mammal macrophages requires more Leish-EVs than those living in insect vectors, since promastigotes incubated at 37 °C released more Leish-EVs than those incubated at 25 °C. Infected THP-1 cells produced high EV concentration (THP-1 cells-EVs) when compared with those from the control group. The same results were obtained when THP-1 cells were treated with Leish-EVs or a crude Leishmania antigen. These data indicated that host-EV concentrations could be used to distinguish infected from uninfected hosts. THP-1 cells treated with Leish-EVs expressed more IL-12 than control THP-1 cells, but were unable to express IFN-γ. These same cells highly expressed IL-10, which inhibited TNF-α and IL-6. Equally, THP-1 cells treated with Leish-EVs up-expressed miR-21-5p and miR-146a-5p. In conclusion, THP-1 cells treated with Leish-EVs highly expressed miR-21-5p and miR-146a-5p and caused the dysregulation of IL-10. Indirectly, these results suggest that high expression of these miRNAs species is caused by Leish-EVs. Consequently, this molecular via can contribute to immunosuppression causing enhanced immunopathology in infected hosts.
RESUMO
PURPOSE: To evaluate the acute hepatotoxicity of Equisentum arvense L. in rats. METHODS: Fifty Wistar rats were used, these being divided in four groups, one being the control (receiving only water) and the other groups receiving graded doses of Equisentum arvense L. (30, 50, and 100mg/kg respectively) for 14 days. Blood samples were obtained to determine TGO, TGP, FA, DHL and GT-gamma activities. After that, hepatic tissue samples were collected for the anatomopathologic analysis. RESULTS: The anatomopathologic exam of the hepatic tissue showed organ with preserved lobular structure. In the same way, there was no significant change in the seric activities of the hepatic enzymes when compared to control group. CONCLUSION: The oral treatment with graded doses of Equisentum arvense L. was not able to produce hepatic changes. Further studies are necessary to evaluate the chronic hepatotoxicity of Equisentum arvense L. in rats.
Assuntos
Equisetum/toxicidade , Fígado/efeitos dos fármacos , Extratos Vegetais/toxicidade , Animais , Fígado/enzimologia , Fígado/patologia , Masculino , Modelos Animais , Extratos Vegetais/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Wistar , Estatísticas não ParamétricasRESUMO
In this work, we evaluate the structural differences of transmembrane helix 3 in rhodopsin and the 5-hydroxytryptamine 1A (5-HT1A) receptor caused by their different amino acid sequence. Molecular dynamics simulations of helix 3 in the 5-HT1A receptor tends to bend toward helix 5, in sharp contrast to helix 3 in rhodopsin, which is properly located within the position observed in the crystal structure. The relocation of the central helix 3 in the helical bundle facilitates the experimentally derived interactions between the neurotransmitters and the Asp residue in helix 3 and the Ser/Thr residues in helix 5. The different amino acid sequence that forms helix 3 in rhodopsin (basically the conserved Gly(3.36)Glu(3.37) motif in the opsin family) and the 5-HT1A receptor (the conserved Cys(3.36)Thr(3.37) motif in the neurotransmitter family) produces these structural divergences. These structural differences were experimentally checked by designing and testing ligands that contain comparable functional groups but at different interatomic distance. We have estimated the position of helix 3 relative to the other helices by systematically changing the distance between the functional groups of the ligands (1 and 2) that interact with the residues in the receptor. Thus, ligand 1 optimally interacts with a model of the 5-HT1A receptor that matches rhodopsin template, whereas ligand 2 optimally interacts with a model that possesses the proposed conformation of helix 3. The lack of affinity of 1 (K(i) > 10,000 nM) and the high affinity of 2 (K(i) = 24 nM) for the 5-HT1A receptor binding sites, provide experimental support to the proposed structural divergences of helix 3 between the 5-HT1A receptor and rhodopsin.
Assuntos
Receptores de Serotonina/metabolismo , Serotoninérgicos/síntese química , Aminoácidos/química , Animais , Asparagina/metabolismo , Ácido Aspártico/metabolismo , Simulação por Computador , Desenho de Fármacos , Técnicas In Vitro , Masculino , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Estrutura Secundária de Proteína , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/química , Receptores de Serotonina/genética , Receptores 5-HT1 de Serotonina , Rodopsina/química , Opsinas de Bastonetes/química , Serotoninérgicos/química , Serotoninérgicos/farmacologiaRESUMO
PURPOSE: To evaluate the acute hepatotoxicity of Equisentum arvense L. in rats. METHODS: Fifty Wistar rats were used, these being divided in four groups, one being the control (receiving only water) and the other groups receiving graded doses of Equisentum arvense L. (30, 50, and 100mg/kg respectively) for 14 days. Blood samples were obtained to determine TGO, TGP, FA, DHL and GT-gamma activities. After that, hepatic tissue samples were collected for the anatomopathologic analysis. RESULTS: The anatomopathologic exam of the hepatic tissue showed organ with preserved lobular structure. In the same way, there was no significant change in the seric activities of the hepatic enzymes when compared to control group. CONCLUSION: The oral treatment with graded doses of Equisentum arvense L. was not able to produce hepatic changes. Further studies are necessary to evaluate the chronic hepatotoxicity of Equisentum arvense L. in rats.
OBJETIVO: Investigar a hepatotoxicidade aguda da Equisetum arvense L. em ratos. MÉTODOS: foram utilizados 50 ratos Wistar, os quais foram divididos em quatro grupos, sendo um controle (recebendo apenas água) e os outros grupos recebendo doses crescentes de cavalinha (30, 50 e 100mg/Kg, respectivamente) por 14 dias. Foram coletadas amostras de sangue para determinação da atividade sérica de TGO, TGP, FA, DHL e gama-GT. Em seguida, foram obtidas amostras de tecido hepático para análise anatomopatológica. RESULTADOS: O exame anatomopatológico de tecido hepático demonstrou órgão com estrutura lobular preservada. Da mesma forma, não houve alteração significativa na atividade sérica das enzimas hepáticas, quando comparado ao grupo controle. CONCLUSÃO: O tratamento com doses crescentes de Equisetum arvense L., não induziu hepatotoxicidade aguda em ratos. Novos estudos são necessários para avaliar a hepatoxicidade crônica de Equisetum arvense L. em ratos.
Assuntos
Animais , Masculino , Ratos , Equisetum/toxicidade , Fígado/efeitos dos fármacos , Extratos Vegetais/toxicidade , Fígado/enzimologia , Fígado/patologia , Modelos Animais , Extratos Vegetais/administração & dosagem , Distribuição Aleatória , Ratos Wistar , Estatísticas não ParamétricasRESUMO
A intervenção coronariana percutânea em tronco de coronária esquerda (TCE) é um grande desafio que, nestes últimos anos com o uso de stents farmacológicos, tem ampliado a sua realização. As angioplastias com implante de stents apresentam resultados técnicos imediatos próximos a 100%, com taxas de mortalidade por todas as causas semelhantes aos resultados cirúrgicos, e essa segurança e novos dispositivos permitem que sejam tratados casos mais complexos, como as lesões de TCE.Relatam-se neste artigo dois casos de angioplastias deTCE não protegido, em pacientes com contra indicação de revascularização cirúrgica, realizadas com implantes de stents convencionais (hospital público), com excelente resultado imediato.
Percutaneous intervention in the left main coronary artery (LMCA) is still a great challenge. However, with the advent of drug-eluting stents, it has become more common over the past few years. Angioplasties with stent implantation present immediate technical outcomes at close to 100% success, with mortality rates from all causes similar to surgical approaches. This safety and new devices allow more complex cases to be treated, such as LMCA lesions. This report addresses two cases of unprotected left main coronary artery angioplasty inpatients counter-indicated for surgical coronary artery bypass graft (CABG) surgery, performed in Brazilian government hospitals using bare metal stents, with excellent immediate outcomes.