RESUMO
The search for chemical compounds extracted from animal and / or plant species has been investigated in experimental tests when considering the treatment of diseases of epidemiological importance such as rabies, a viral, acute and infectious disease, which has a lethality of approximately 100% and which has been a major cause of death in humans with respect to infectious diseases. This study aimed to investigate the mechanism of action of the alkaloid bufotenine in an in vivo model with the rabies virus. The production and titration of wild virus was carried out from the IP1972 / 16 sample (compatible with domestic dog) in an animal for later carrying out the accidental simulation experiment with the rabies virus inoculated via footpad. Six animals were used to produce suspensions, 40 for titration and 75 for the experiment. The virus titer was 1DL50 = 102.4, and administration of a total of 10 LD50 was established. The CNS, bone marrow and whole blood of the animals were collected. The CNS of each animal was subjected to titration of virus in suspension, analysis of cytokines and histological analysis; the marrow was subjected to titration of virus in suspension; the whole blood was subjected to the Rapid Fluorescent Spot Inhibition Test (RFFIT) and to the analysis of cytokines. The results revealed a possible effect of bufotenine in modulating the immune response of the studied host, allowing to suggest an interference in delaying the manifestation of symptoms. As for the histological analysis of the Central Nervous System (CNS) of the animals, bufotenine possibly prevented the presence of inflammatory infiltrate of mononuclear cells in the meningeal region when compared to the positive control group for rabies and also possibly contributed to the reduction of neuronal degeneration. This work was a pioneer in conducting research that associates the use of the bufotenin toxin extracted from the seed of a plant representative of the Brazilian flora, the angicobranco, as an antiviral applied to the study of the effects on the immunological aspects of the host infected by the rabies, and that, therefore, needs further studies for further clarification.
A busca por compostos químicos extraídos de espécies animais e ou vegetais tem sido investigada em testes experimentais quando se tem em vista o tratamento de doenças de importância epidemiológica como a raiva, uma doença viral, aguda e infecciosa, que apresenta letalidade de aproximadamente 100% e que tem sido uma das principais causas de morte em humanos no que se refere às doenças infecciosas. O presente trabalho teve como objetivo investigar o mecanismo de ação do alcaloide bufotenina em modelo in vivo com o vírus da raiva. Foi realizada a produção e a titulação de vírus selvagem a partir da amostra IP1972/16 (linhagem genética compatível com cão doméstico) em animal para posterior realização do experimento de simulação acidental com o vírus da raiva inoculado via coxim plantar. Foram utilizados 6 animais para produção de suspensões, 40 para titulação e 75 no experimento. O título do vírus foi de 1DL50= 102,4, e foi estabelecida a administração do total de 10 DL50. Foram coletados o SNC, medula e o sangue total dos animais. O SNC de cada animal foi submetido à titulação de vírus em suspensão, análise de citocinas e análise histológica; a medula foi submetida à titulação de vírus em suspensão; o sangue total foi submetido ao Teste Rápido de Inibição de Focos Fluorescentes (RFFIT) e à análise de citocinas. Os resultados revelaram uma possível atuação da bufotenina na modulação da resposta imunológica do hospedeiro estudado permitindo sugerir uma interferência no retardo da manifestação dos sintomas. Quanto à análise histológica do Sistema Nervoso Central (SNC) dos animais, a bufotenina possivelmente impediu a presença de infiltrado inflamatório de células mononucleares na região da meninge quando comparado ao grupo controle positivo para raiva e também contribuiu possivelmente para a redução da degeneração neuronal. Este trabalho foi pioneiro na condução de uma pesquisa que associa o uso da toxina bufotenina extraída da semente de uma planta representante da flora brasileira, o angico-branco, como um antiviral aplicado ao estudo dos efeitos sobre os aspectos imunológicos do hospedeiro infectado pelo vírus da raiva, e que portanto, necessita da continuidade de estudos para maiores esclarecimentos.
RESUMO
Background: Between 40,000-70,000 people die yearly of rabies, an incurable disease. Besides post-bite vaccination, no treatment is available for it. Methods: First, virus dilution for antiviral effects in mice was determined. Then, animals were treated as follows: control (NaCl 250 µL/animal/day); bufotenine (0.63, 1.05 and 2.1 mg in 250 µL of NaCl/animal/day); rabies (10-6,82CVS dilution); and test (10-6,82 CVS dilution and bufotenine, in the above-mentioned doses). Animals were observed daily for 21 days or until the 3rd stage of rabies infection. Twitch-tension and liposome studies were applied to understand the possible interaction of bufotenine with receptors, particularly acetylcholine. Results: Bufotenine was able to increase the survival rate of intracerebrally virus-infected mice from 15 to 40%. Bufotenine did not seem to interfere with the acetylcholine response in the skeletal muscle, indicating that its mechanism of action is not blocking the virus entrance due to nAChR antagonism. By analyzing liposomes, we could observe that bufotenine did not passively penetrates cell membranes, indicating the necessity of complementary structures to cell penetration. Conclusions: Bufotenine is a promising candidate for drug development. After further chemical modification, it might be possible to dissociate minor side effects, increase efficiency, efficacy and pharmacokinetics, yielding a true anti-rabies drug.
RESUMO
Rabies virus (RABV) does not persist in the environment as it is a very fragile agent. The primary hosts are mammalian species in the orders Carnivora and Chiroptera. Since the late 1980s, RABV has been isolated from non-human primates, Callithrix jacchus (the white-tufted marmoset), in four coastal states (Rio Grande do Norte, Ceará, Piauí and Pernambuco) in north-eastern Brazil, where this species is indigenous. The original habitat of C. jacchus consisted of two Brazilian biomes, the Atlantic Forest and the Caatinga. However, these marmosets have since adapted to other ecosystems as a result of human activities. Between 1988 and 1989, RABV isolates were obtained from white-tufted marmosets in the state of Rio Grande do Norte, but antigenic and genetic identification studies were not conducted at that time. In the following years, three additional states reported cases (Ceará, Piauí and Pernambuco). In two of these states (Ceará and Piauí), human cases of rabies transmitted by marmosets were reported. According to Brazilian Health Ministry data, at least 19 human cases in which this species was the source of infection were registered in between 1990 and 2016. Recent findings in laboratory tests of 12 rabid samples from humans and marmosets and the regional transmission among these animals for over 20 years, together with the gradual increase in the affected geographic area, support the concept of the emergence of a new RABV reservoir. Regional tourism, the wild animal trade and the cultural practice of maintaining these animals as pets, particularly in coastal regions, appear to be major risk factors for the increase in human cases. Additional epidemiological and ecological studies are required to better understand local disease dynamics and to identify ideal opportunities for prevention and control of this fatal infection.
Assuntos
Callithrix , Reservatórios de Doenças/veterinária , Doenças dos Macacos/virologia , Vírus da Raiva/isolamento & purificação , Raiva/veterinária , Substituição de Aminoácidos , Animais , Antígenos Virais , Brasil/epidemiologia , Reservatórios de Doenças/virologia , Genoma Viral , Humanos , Doenças dos Macacos/epidemiologia , Filogenia , Raiva/epidemiologia , Raiva/virologia , Vírus da Raiva/genéticaRESUMO
Rabies virus (RABV) does not persist in the environment as it is a very fragile agent. The primary hosts are mammalian species in the orders Carnivora and Chiroptera. Since the late 1980s, RABV has been isolated from non-human primates, Callithrix jacchus (the white-tufted marmoset), in four coastal states (Rio Grande do Norte, Ceará, Piauí and Pernambuco) in north-eastern Brazil, where this species is indigenous. The original habitat of C. jacchus consisted of two Brazilian biomes, the Atlantic Forest and the Caatinga. However, these marmosets have since adapted to other ecosystems as a result of human activities. Between 1988 and 1989, RABV isolates were obtained from white-tufted marmosets in the state of Rio Grande do Norte, but antigenic and genetic identification studies were not conducted at that time. In the following years, three additional states reported cases (Ceará, Piauí and Pernambuco). In two of these states (Ceará and Piauí), human cases of rabies transmitted by marmosets were reported. According to Brazilian Health Ministry data, at least 19 human cases in which this species was the source of infection were registered in between 1990 and 2016. Recent findings in laboratory tests of 12 rabid samples from humans and marmosets and the regional transmission among these animals for over 20 years, together with the gradual increase in the affected geographic area, support the concept of the emergence of a new RABV reservoir. Regional tourism, the wild animal trade and the cultural practice of maintaining these animals as pets, particularly in coastal regions, appear to be major risk factors for the increase in human cases. Additional epidemiological and ecological studies are required to better understand local disease dynamics and to identify ideal opportunities for prevention and control of this fatal infection.
RESUMO
Rabies virus (RABV) does not persist in the environment as it is a very fragile agent. The primary hosts are mammalian species in the orders Carnivora and Chiroptera. Since the late 1980s, RABV has been isolated from nonhuman primates, Callithrix jacchus (the whitetufted marmoset), in four coastal states (Rio Grande do Norte, Ceará, Piauí and Pernambuco) in northeastern Brazil, where this species is indigenous. The original habitat of C. jacchus consisted of two Brazilian biomes, the Atlantic Forest and the Caatinga. However, these marmosets have since adapted to other ecosystems as a result of human activities. Between 1988 and 1989, RABV isolates were obtained from whitetufted marmosets in the state of Rio Grande do Norte, but antigenic and genetic identification studies were not conducted at that time. In the following years, three additional states reported cases (Ceará, Piauí and Pernambuco). In two of these states (Ceará and Piauí), human cases of rabies transmitted by marmosets were reported. According to Brazilian Health Ministry data, at least 19 human cases in which this species was the source of infection were registered in between 1990 and 2016. Recent findings in laboratory tests of 12 rabid samples from humans and marmosets and the regional transmission among these animals for over 20 years, together with the gradual increase in the affected geographic area, support the concept of the emergence of a new RABV reservoir. Regional tourism, the wild animal trade and the cultural practice of maintaining these animals as pets, particularly in coastal regions, appear to be major risk factors for the increase in human cases. Additional epidemiological and ecological studies are required to better understand local disease dynamics and to identify ideal opportunities for prevention and control of this fatal infection. (AU)
Assuntos
Vírus da Raiva/isolamento & purificação , Raiva , Brasil , Zoonoses , Callitrichinae , Lyssavirus , Doenças Transmissíveis EmergentesRESUMO
Cases of canine rabies continue to occur in North and Northeast Brazil, and the number of notifications of rabies cases in wild canids has increased as a result of the expansion of urban areas at the expense of areas with native vegetation. In light of this, we performed molecular characterization of rabies virus isolates from dogs and Cerdocyon thous from various states in North and Northeast Brazil. In all, 102 samples from dogs (n = 56) and Cerdocyon thous (n = 46) collected between 2006 and 2012 were used. The nucleotide sequences obtained for the N gene of rabies virus were analyzed, and phylogenetic analysis revealed the presence of two distinct genetic lineages, one associated with canids and one with bats, and, within the canid cluster, two distinct sublineages circulating among dogs and Cerdocyon thous. In addition, phylogenetic groups associated with geographic region and fourteen cases of interspecific infection were observed among the isolates from canids. Our findings show that analysis of rabies virus lineages isolated from reservoirs such as canids must be constantly evaluated because the mutation rate is high.