RESUMO
The rational design and synthesis of a series of 5-nitro-2-furoic acid analogues are presented. The trypanocidal activity against epimastigote forms of Trypanosoma cruzi and the toxic effects on human HeLa cells were tested. Between all synthetic compounds, three of thirteen had an IC50 value in the range of Nfx, but compound 13 exhibited an improved effect with an IC50 of 1.0 ± 0.1 µM and a selective index of 70 in its toxicity against HeLa cells. We analyzed the activity of compounds 8, 12 and 13 to interfere in the central redox metabolic pathway in trypanosomatids, which is dependent of reduced trypanothione as the major pivotal thiol. The three compounds behaved as better inhibitors of trypanothione reductase than Nfx (Ki values of 118 µM, 61 µM and 68 µM for 8, 12 and 13, respectively, compared with 245 µM for Nfx), all following an uncompetitive enzyme inhibition pattern. Docking analysis predicted a binding of inhibitors to the enzyme-substrate complex with binding energy calculated in-silico that supports such molecular interaction.
Assuntos
NADH NADPH Oxirredutases/antagonistas & inibidores , Nitrofuranos/química , Nitrofuranos/farmacologia , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/enzimologia , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Desenho de Fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Células HeLa , Humanos , Simulação de Acoplamento Molecular , NADH NADPH Oxirredutases/metabolismo , Trypanosoma cruzi/efeitos dos fármacosRESUMO
RATIONALE: During binocular rivalry, two incompatible images are presented to each eye and these monocular stimuli compete for perceptual dominance, with one pattern temporarily suppressed from awareness. One variant of stimulus presentation in binocular rivalry experiments is dichoptic stimulus alternation (DSA), when stimuli are applied to the eyes in rapid reversals. There is preliminary report that in contrast with healthy controls, schizophrenic patients can maintain binocular rivalry even at very high DSA rates. OBJECTIVE: The study was undertaken to investigate whether binocular rivalry survives high rates of DSA induced by the South American hallucinogenic beverage ayahuasca. METHODS: Ten individuals who were participating in ayahuasca ceremonials were requested to volunteer for binocular rivalry tests (DSA=0, 3.75, 7.5, 15 and 30 Hz) without and after drinking the brew. RESULTS: Ingestion of ayahuasca increased mean dominance periods both in standard binocular rivalry conditions (no DSA) and tests with DSA. At higher DSA rates (15 and 30 Hz) the total length of dominance periods was longer on the brew. CONCLUSION: It is discussed that ayahuasca-induced survival of binocular rivalry at high DSA rates may be related to slow visual processing and increased mean dominance periods may result from hallucinogen-induced alteration of gamma oscillations in the visual pathways.
Assuntos
Banisteriopsis/química , Alucinógenos/efeitos adversos , Disparidade Visual/efeitos dos fármacos , Visão Binocular/efeitos dos fármacos , Percepção Visual/efeitos dos fármacos , Adulto , Idoso , Feminino , Alucinógenos/farmacologia , Harmina/efeitos adversos , Harmina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/métodos , Extratos Vegetais/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Disparidade Visual/fisiologia , Visão Binocular/fisiologia , Percepção Visual/fisiologiaRESUMO
In the city of Iquitos and its vicinity there is even today a rich tradition of folk medicine. Practitioners, some of whom qualify as shamans, make an important contribution to the psychosomatic health of the inhabitants of this area. Among them there are those called vegetalistas or plant specialists and who use a series of plants called doctores or plant teachers. It is their belief that if they fulfill certain conditions of isolation and follow a prescribed diet, these plants are able to "teach" them how to diagnose and cure illnesses, how to perform other shamanic tasks, usually through magic melodies or icaros, and how to use medicinal plants. Four shamans were questioned about the nature and identity of these magic plants, what are the dietary prescriptions to be followed, how the transmission of shamanic power takes place, the nature of their helping spirits, and the function of the magic melodies or icaros given to them by the plant teachers.
Assuntos
Medicina Tradicional , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Música , PeruRESUMO
The use of psychotropic plants among the mestizo population of the northwestern Amazon has already been the subject of some research. However, the field is far from fully investigated. Practitioners locally known by the name of "vegetalistas" or simply "maestros" have preserved considerable knowledge of plant lore, and still today contribute substantially to the health care of both rural and urban population. The present paper is based on field work with one particular such practitioner, Don Emilio Andrade Gómez, a 65-year-old shaman who lives in the vicinity of Iquitos (3 degrees 50S 73 degrees 15W), northeastern Peru. Some of the basic ideas of his cosmovision are presented. Special attention is given to the concept of "doctor" or "plant teacher", applied to certain plants which are supposed to "teach medicine", if the appropriate conditions of isolation and diet are observed. Some of these plants are added to the hallucinogenic beverage known in the region by the Quéchua name ayahuasca, made from the stem of Banisteriopsis species, and one or several additives. During the period of isolation the spirits of these plants teach the initiate certain melodies or "icaros" that he will later use when practising his shamanistic activities. During field work in 1981 and 1982 the author collected various specimens of "plant teachers", part of which have now been identified, and are also presented.