Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
Mais filtros











Intervalo de ano de publicação
1.
HardwareX ; 19: e00540, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38988372

RESUMO

Recently, a novel method for the growth inhibition of malaria parasites using microwaves was proposed. However, the apparatuses used to demonstrate this method are high-cost and immovable, hindering the progression in this field of research, which is still in its early stages. This paper presents the redesign, construction, and validation of an equivalent system, converting it into a portable and low-cost system, capable of replacing the existing one. The proposed system is mainly composed of an RF generator (MAX2870), an RF amplifier (SKYWORKS 66292-11) and a graphical user interface. Likewise, the RF applicator proposed by the original study was redesigned, resulting in a five-fold improvement in return loss. The obtained results indicate that the proposed system achieves 90% parasite growth inhibition, matching the performance of its counterpart at less than 1% of its cost. These results represent a breakthrough for the creation of smaller, enhanced devices that open new possibilities for an alternative treatment to combat this devastating disease.

2.
Micromachines (Basel) ; 15(5)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38793163

RESUMO

Pathological processes often change the mechanical properties of cells. Increased rigidity could be a marker of cellular malfunction. Erythrocytes are a type of cell that deforms to squeeze through tiny capillaries; changes in their rigidity can dramatically affect their functionality. Furthermore, differences in the homeostatic elasticity of the cell can be used as a tool for diagnosis and even for choosing the adequate treatment for some illnesses. More accurate types of equipment needed to study biomechanical phenomena at the single-cell level are very costly and thus out of reach for many laboratories around the world. This study presents a simple and low-cost technique to study the rigidity of red blood cells (RBCs) through the application of electric fields in a hand-made microfluidic chamber that uses a capacitor principle. As RBCs are deformed with the application of voltage, cells are observed under a light microscope. From mechanical force vs. deformation data, the elastic constant of the cells is determined. The results obtained with the capacitor-based method were compared with those obtained using optical tweezers, finding good agreement. In addition, P. falciparum-infected erythrocytes were tested with the electric field applicator. Our technique provides a simple means of testing the mechanical properties of individual cells.

3.
Cells ; 13(4)2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38391947

RESUMO

Plasmodium parasites need to find red blood cells (RBCs) that, on the one hand, expose receptors for the pathogen ligands and, on the other hand, maintain the right geometry to facilitate merozoite attachment and entry into the red blood cell. Both characteristics change with the maturation of erythrocytes. Some Plasmodia prefer younger vs. older erythrocytes. How does the life evolution of the RBC affect the invasion of the parasite? What happens when the RBC ages? In this review, we present what is known up until now.


Assuntos
Malária Falciparum , Plasmodium falciparum , Humanos , Envelhecimento Eritrocítico , Malária Falciparum/parasitologia , Eritrócitos/parasitologia , Proteínas de Transporte
4.
Front Cell Infect Microbiol ; 13: 955134, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816585

RESUMO

Malaria, which infected more than 240 million people and killed around six hundred thousand only in 2021, has reclaimed territory after the SARS-CoV-2 pandemic. Together with parasite resistance and a not-yet-optimal vaccine, the need for new approaches has become critical. While earlier, limited, studies have suggested that malaria parasites are affected by electromagnetic energy, the outcomes of this affectation vary and there has not been a study that looks into the mechanism of action behind these responses. In this study, through development and implementation of custom applicators for in vitro experimentation, conditions were generated in which microwave energy (MW) killed more than 90% of the parasites, not by a thermal effect but via a MW energy-induced programmed cell death that does not seem to affect mammalian cell lines. Transmission electron microscopy points to the involvement of the haemozoin-containing food vacuole, which becomes destroyed; while several other experimental approaches demonstrate the involvement of calcium signaling pathways in the resulting effects of exposure to MW. Furthermore, parasites were protected from the effects of MW by calcium channel blockers calmodulin and phosphoinositol. The findings presented here offer a molecular insight into the elusive interactions of oscillating electromagnetic fields with P. falciparum, prove that they are not related to temperature, and present an alternative technology to combat this devastating disease.


Assuntos
COVID-19 , Malária Falciparum , Malária , Parasitos , Animais , Humanos , Micro-Ondas , SARS-CoV-2 , Malária Falciparum/parasitologia , Plasmodium falciparum , Mamíferos
5.
Molecules ; 29(1)2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38202779

RESUMO

Amphibians are widely known as a prolific source of bioactive metabolites. In this work, we isolated and characterized compounds with antiparasitic activity from the oocytes of the toad Rhinella alata collected in Panama. Bio-guided isolation and structural elucidation were carried out using chromatographic and spectroscopic techniques, respectively. The organic extract was subjected to solid phase extraction followed by HPLC purification of the fraction with in vitro activity against Trypanosoma cruzi trypomastigotes. Seven steroids (1-7) of the bufadienolide family were isolated, and their structures were determined using NMR and MS analyses; of these 19-formyl-dyscinobufotalin, (3) is reported as a new natural product. Compounds 1 and 3-7 resulted in a good anti-trypanosomal activity profile. Among these, 16ß-hydroxyl-hellebrigenin (1) and bufalin (7) showed significant selectivity values of >5 and 2.69, respectively, while the positive control benznidazole showed a selectivity of 18.81. Furthermore, molecular docking analysis showed compounds 1, 3 and 7 interact through H-bonds with the amino acid residues GLN-19, ASP-158, HIS-159 and TRP-177 from cruzipain at the catalytic site. Given the lack of therapeutic options to treat American trypanosomiasis, this work can serve as the basis for further studies that aim for the development of bufadienolides or their derivatives as drugs against Chagas disease.


Assuntos
Bufanolídeos , Doença de Chagas , Trypanosoma cruzi , Animais , Bufonidae , Simulação de Acoplamento Molecular , Oócitos , Bufanolídeos/farmacologia , Doença de Chagas/tratamento farmacológico
6.
J Photochem Photobiol B ; 223: 112283, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34537542

RESUMO

BACKGROUND: In vitro and in vivo testing of new technology was performed to evaluate the antiplasmodial activity of Photonic Multiphase Modulators (PMM) in cultures and in mice previously infected with Plasmodium falciparum and Plasmodium berghei parasites. METHODS: Cultures of P. falciparum infected-erythrocytes were exposed overnight to two generations of different APSE™ and BioPhoton-X™ PMM (C#1, R#1, R#2, D8 and D9). Growth of parasites was determined through flow cytometry or microscopy. Mice of the strain C57BL/6 were infected and treated with water exposed to second-generation APSE™ and BioPhoton-X™ PMM plus one previously untested first-generation PMM (AGN10). Parasitemia and weight loss were monitored throughout the infection until death or point of euthanasia was reached. After death, necropsy was performed on all animals and the number of days each survived was recorded. RESULTS: In vitro and in vivo testing using different APSE™- and BioPhoton-X™-designed PMM revealed an effect of D8 in lowering the growth of the parasite in vitro, while the best effect in mice was observed with D9 PMM, with a reduced weight loss and an increase in survival, although the results in lowering the parasitemia were inconclusive. D9 PMM did not generate ROS in vitro. CONCLUSIONS: APSE™ and BioPhoton-X™ optic circuit technologies can affect the growth of parasites and show protective effects in mice drinking from water treated with their PMM.


Assuntos
Antimaláricos/química , Água/química , Animais , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Eritrócitos/parasitologia , Malária/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óptica e Fotônica/métodos , Plasmodium berghei/efeitos dos fármacos , Plasmodium berghei/metabolismo , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/metabolismo , Espécies Reativas de Oxigênio/metabolismo
7.
Molecules ; 26(14)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34299492

RESUMO

Toads in the family Bufonidae contain bufadienolides in their venom, which are characterized by their chemical diversity and high pharmacological potential. American trypanosomiasis is a neglected disease that affects an estimated 8 million people in tropical and subtropical countries. In this research, we investigated the chemical composition and antitrypanosomal activity of toad venom from Rhinella alata collected in Panama. Structural determination using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy led to the identification of 10 bufadienolides. Compounds identified include the following: 16ß-hydroxy-desacetyl-bufotalin-3-adipoyl-arginine ester (1), bufotalin (2), 16ß-hydroxy-desacetyl-bufotalin-3-pimeloyl-arginine ester (3), bufotalin-3-pimeloyl-arginine ester (4), 16ß-hydroxy-desacetyl-bufotalin-3-suberoyl-arginine ester (5), bufotalin-3-suberoyl-arginine ester (6), cinobufagin-3-adipoyl-arginine ester (7), cinobufagin-3-pimeloyl-arginine ester (8), cinobufagin-3-suberoyl-arginine ester (9), and cinobufagin (10). Among these, three new natural products, 1, 3, and 5, are described, and compounds 1-10 are reported for the first time in R. alata. The antitrypanosomal activity assessed in this study revealed that the presence of an arginyl-diacid attached to C-3, and a hydroxyl group at C-14 in the structure of bufadienolides that is important for their biological activity. Bufadienolides showed cytotoxic activity against epithelial kidney Vero cells; however, bufagins (2 and 10) displayed low mammalian cytotoxicity. Compounds 2 and 10 showed activity against the cancer cell lines MCF-7, NCI-H460, and SF-268.


Assuntos
Antiprotozoários/farmacologia , Bufanolídeos/farmacologia , Bufonidae/metabolismo , Pele/metabolismo , Venenos de Anfíbios/metabolismo , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Chlorocebus aethiops , Humanos , Células MCF-7 , Espectrometria de Massas/métodos , Panamá , Trypanosoma cruzi , Células Vero
8.
J Nat Prod ; 84(5): 1434-1441, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-33979168

RESUMO

In this study, eight natural isocoumarins (1-8) were isolated from a marine-derived Exserohilum sp. fungus. To explore their structure-activity relationship and discover potent antimalarial leads, a small library of 22 new derivatives (1a-1n, 2a, 3a-3c, 4a-4c, and 7a) were semisynthesized by varying the substituents of the aromatic ring and the aliphatic side chains. The natural compound (1) and three semisynthetic derivatives (1d, 1n, and 2a), possessing an all-cis stereochemistry, exhibited strong antiplasmodial activity with IC50 values of 1.1, 0.8, 0.4, and 2.6 µM, respectively. Mechanism studies show that 1n inhibits hemozoin polymerization and decreases the mitochondrial membrane potential but also inhibits P. falciparum DNA gyrase. 1n not only combines different mechanisms of action but also exhibits a high therapeutic index (CC50/IC50 = 675), high selectivity, and a notable drug-like profile.


Assuntos
Antimaláricos/farmacologia , Ascomicetos/química , Isocumarinas/farmacologia , Animais , Antozoários/microbiologia , Antimaláricos/síntese química , Organismos Aquáticos/química , China , Chlorocebus aethiops , DNA Girase , Hemeproteínas , Isocumarinas/síntese química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Inibidores da Topoisomerase II/farmacologia , Células Vero
9.
Sci Rep ; 10(1): 12717, 2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-32719474

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

10.
J Parasit Dis ; 44(2): 305-313, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32499668

RESUMO

Plasmodium falciparum (P. falciparum) malaria presents serious public health problems worldwide. The parasite´s resistance to antimalarial drugs has proven to be a significant hurdle in the search for effective treatments against the disease. For this reason, the study of natural products to find new antimalarials remains a crucial step in the fight against malaria. In this study, we aimed to study the in vivo performance of the decoction of C. nucifera leaves in P. berghei-infected mice. We analyzed the effectiveness of different routes of administration and the acute toxicity of the extract. Additionally, we determined the suppressive, curative and prophylactic activity of the extract. The results showed that the decoction of leaves of C. nucifera is most effective when administered intramuscularly to mice in comparison to intraperitoneal, subcutaneous and intragastric methods. We also found that organ signs of acute toxicity appear at 2000 mg/kg/day as evidenced by necropsy examination. Additionally, we found that the prophylactic effect of the extract is of 48% inhibition, however, there is no curative effect. Finally, in a 4-day suppressive assay, we found that the extract can inhibit the growth of the parasite by up to 54% at sub-toxic doses when administered intramuscularly.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA