Bufotenine, a tryptophan-derived alkaloid, suppresses the symptoms and increases the survival rate of rabies-infected mice: the development of a pharmacological approach for rabies treatment

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.(AU)

Synanthropic rodents as virus reservoirs and transmitters

Abstract This review focuses on reports of hepatitis E virus, hantavirus, rotavirus, coronavirus, and arenavirus in synanthropic rodents (Rattus rattus, Rattus norvegicus, and Mus musculus) within urban environments. Despite their potential impact on human health, relatively few studies have addressed the monitoring of these viruses in rodents. Comprehensive control and preventive activities should include actions such as the elimination or reduction of rat and mouse populations, sanitary education, reduction of shelters for the animals, and restriction of the access of rodents to residences, water, and food supplies.

Patogenicidad oral de un aislamiento autóctono del hongo entomopatógeno Beauveria bassiana en ratones (Mus musculus, cepa NMRI) / Oral pathogenicity of an autochthonous isolate of the entomopathogenic fungus Beauveria bassiana in mice (Mus musculus, strain NMRI)

Se evaluó a concentración de 1x10(8) conidias/mL por vía oral en ratones albinos NMRI, la patogenicidad del aislamiento fúngico LF14 de Beauveria bassiana, el cual posee una elevada virulencia hacia Rhodnius prolixus y Triatoma maculata (Triatominae), vectores de enfermedad de Chagas en Venezuela. Se hicieron observaciones clínicas diarias. Se estimó el aclaramiento fúngico mediante examen directo y cultivo de muestras de heces, y de infectividad con la toma de muestras de tejidos y estudio histopatológico. No se registró muertes ni alteraciones clínico-patológicas, y el comportamiento en todos los animales fue activonormal. El peso promedio corporal, tanto en los animales expuestos a LF14 B. bassiana como los controles, se incrementó con el tiempo, siendo sólo las diferencias entre sexos estadísticamente significativas (P<0,0000). Se obtuvieron conidias viables en heces hasta el día 7 después del consumo del hongo. No se detectó anormalidades en la inspección anatomopatológico ni conidias germinadas en ninguno de los órganos estudiados, sin ninguna reacción tisular patológica, sugiriendo que no existe evidencia de multiplicación fúngica. Los resultados obtenidos permiten concluir que el aislamiento LF14 de B. bassiana no es patogénico cuando se administró por vía oral en ratones albinos NMRI.

This study evaluated concentrations of 1x10(8) conidia/mL orally administered in white mice (NMRI strain, males and females), pathogenicity of a native isolate LF14 of Beauveria bassiana (Fungi: Ascomycota), highly virulent to Rhodnius prolixus and Triatoma maculata (Triatominae), vectors of Chagas disease in Venezuela. Clinical evaluations were done daily. Clearance of fungus in the faeces was estimated by direct examination and culturing, and infectivity by performing mycological and histopathological tests.Animals showed no discernible pathological changes or death and had 100% active-normal behaviour. In all the mice groups, including control ones, there was an increase in the mean weight gained through time, with statistically significance difference between the sexes (P<0,0000). Viable conidia were observed in faeces until 7 days after consuming the fungus. Anatomopathological changes or germinated conidia were not detected in analysed organs, with normal tissue reactions, suggesting no evidence for fungal multiplication. Results obtained allowed us to conclude that isolate LF14 B. bassiana orally administered is safe and non pathogenic in white mice (NMRI strain).

Vírus da raiva em quirópteros naturalmente infectados no Estado de São Paulo, Brasil / Rabies virus in naturally infected bats in the State of São Paulo, Southeastern Brazil

OBJETIVO: Identificar as espécies de morcegos envolvidas na manutenção do ciclo da raiva, verificar a distribuição do vírus da raiva em tecidos e órgãos de morcegos e os períodos de mortalidade dos camundongos inoculados. MÉTODOS: A positividade para o vírus da raiva foi avaliada por imunofluorescência direta em morcegos de municípios do Estado de São Paulo, de abril de 2002 a novembro de 2003. A distribuição do vírus nos morcegos foi avaliada pela inoculação de camundongos e infecção de células N2A, com suspensões a 20 por cento preparadas a partir de fragmentos de diversos órgãos e tecidos, além de cérebro e glândula salivar. A mortalidade dos camundongos foi observada diariamente, após inoculação intracerebral. RESULTADOS: Dos 4.393 morcegos pesquisados, 1,9 por cento foram positivos para o vírus da raiva, pertencentes a dez gêneros, com predomínio de insetívoros. A média do período máximo de mortalidade dos camundongos pós-inoculação a partir de cérebros e glândulas salivares de morcegos hematófagos foi de 15,33±2,08 dias e 11,33±2,30 dias; insetívoros, 16,45±4,48 dias e 18,91±6,12 dias; e frugívoros, 12,60±2,13 dias e 15,67±4,82 dias, respectivamente. CONCLUSÕES: As espécies infectadas com o vírus da raiva foram: Artibeus lituratus, Artibeus sp., Myotis nigricans, Myotis sp., Eptesicus sp., Lasiurus ega, Lasiurus cinereus, Nyctinomops laticaudatus, Tadarida brasiliensis, Histiotus velatus, Molossus rufus, Eumops sp. e Desmodus rotundus. A pesquisa de vírus em diferentes tecidos e órgãos mostrou-se que os mais apropriados para o isolamento foram cérebro e glândulas salivares.

OBJECTIVE: To identify the species of bats involved in maintaining the rabies cycle; to investigate the distribution of the rabies virus in the tissues and organs of bats and the time taken for mortality among inoculated mice. METHODS: From April 2002 to November 2003, bats from municipalities in the State of São Paulo were screened for the presence of the rabies virus, by means of direct immunofluorescence. The virus distribution in the bats was evaluated by inoculating mice and N2A cells with 20 percent suspensions prepared from fragments of different organs and tissues, plus the brain and salivary glands. The time taken for mortality among the mice was monitored daily, following intracerebral inoculation. RESULTS: Out of the 4,395 bats received, 1.9 percent were found positive for the rabies virus. They belonged to ten genera, with predominance of insectivores. The maximum mean times taken for mortality among the mice following inoculation with brain and salivary gland material were 15.33±2.08 days and 11.33±2.30 days for vampire bats, 16.45±4.48 days and 18.91±6.12 days for insectivorous bats, and 12.60±2.13 days and 15.67±4.82 days for frugivorous bats, respectively. CONCLUSIONS: The species infected with the rabies virus were: Artibeus lituratus, Artibeus sp., Myotis nigricans, Myotis sp., Eptesicus sp., Lasiurus ega, Lasiurus cinereus, Nyctinomops laticaudatus, Tadarida brasiliensis, Histiotus velatus, Molossus rufus, Eumops sp. and Desmodus rotundus. Virus investigation in the different tissues and organs showed that the brain and salivary glands were the most suitable sites for virus isolation.

Genes de susceptibilidad/resistencia a Flavivirus, implicaciones en la severidad de la infeccion / Susceptibility/Resistance Genes to Flavivirus, Implications on Disease Severity

Las infecciones transmitidas por Flavivirus se encuentran entre las enfermedades transmisibles con mayor incidencia en el mundo. La mayoría de ellas se manifiestan clínicamente como un síndrome febril que puede estar o no acompañado de diversos síntomas. La severidad de estas infecciones es variable con casos asintomáticos y otros que pueden llegar a ser letales. La razón de esta variabilidad en la presentación clínica, se desconoce en humanos. En ratones se han identificado cepas susceptibles y cepas resistentes a la infección por algunos Flavivirus. Por clonación posicional se mapeó el gen responsable de la resistencia a virus West Nile en el cromosoma 5 de ratón y se identificó como oligoadenilato sintetasa 1b (Oas1b). Este gen codifica una proteína que sintetiza oligómeros de adenina que activan la RNasaL, que a su vez degrada los RNAs virales. Células provenientes de ratones resistentes a la infección por Flavivirus producen menor cantidad de virus que su contraparte susceptible. Recientemente en humanos, se identificó un polimorfismo asociado con susceptibilidad a infección por virus West Nile en el gen de OasL. Sin embargo, el mecanismo bioquímico y molecular exacto por el cual se produce la susceptibilidad no ha sido completamente dilucidado. Este conocimiento permitiría aclarar aspectos de la fisiopatología de estas enfermedades y enfocar la terapéutica desde un punto de vista más específico.

Presença de Bunyavirus (Sorogrupo Bunyamwera) no Estado de Säo Paulo, Brasil / Presence of Bunyaviruses (Bunyamwera Serogroup) in Säo Paulo State, Brazil

Sete vírus foram isolados de camundongos sentinela, expostos em área de floresta, na Regiäo da Mata Atântica, Estado de Säo Paulo, Brasil, de 1974 a 1981. Estäo incluidas cinco amostras de Maguari, uma Kairi e uma de Tucunduba. Foi a primeira vez que esses vírus foram detectados no Estado de Säo Paulo. Os isolados foram identificados por testes sorológicos de Hemaglutinaçäo, Inibiçäo de Hemaglutinaçäo, Fixaçäo de Complemento e Neutralizaçäo em camundongos lactentes. Os resultados mostram que esses vírus pertencem os sorogrupo Bunyamwera. Como existem relatos de doença humana causada por vírus pertencente a esse grupo, conclue-se que é necessário estudar os aspectos ecológicos envolvendo os ciclos de manutençäo desses vírus, assim como a possibilidade de sua transmissäo em seres humanos no Estado de Säo Paulo, Brasil

Toxoplasma gondii (Eucoccidia: Sarcoystidae) dissemination pattern in rats after oral infection with oocysts of an avirulent strain

Differences in Toxoplasma gondii dissemination in white rats (Sprague Dowley) and mice (Wistar) after oral oocyst inoculation are described. Groups of five animals (both hosts) wewe infected por os with oocyts of the TCR-2 avirulent strain and the dissemination pattern was compared in brain tissue or by serology. Early disseminationwas similar in both species. One hr after infection the parasite was present in blood and peritoneal exudate as well as in heart, lung, liver, spleen, lymph nodes and brain. However, after five days there were important differences between both hosts and after 30 days, the parasite was detected only in rat heart and brain, while in mice it persisted in fluids and all organs.

Rabies virus infection of cultured adult mouse dorsal root ganglion neurons

An in vitro model of adult dorsal root ganglion neurons infection by rabies virus is described. Viral marked neurotropism is observed, and the percentage and the degree of infection of the neurons is higher than in non neuronal cells, even if neurons are the minority of the cells in the culture. The neuritic tree is also heavily infected by the virus.

Mammary adenocarcinoma of viral genesis in CF-1 mice

No biotério de pequenos animais da Fundaçäo Ezequiel Dias verificou-se em camundongos frequência mensal média de 0,83 por cento de nódulos tumorais subcutâneos, entre abril de 1991 e julho de 1992. Os achados macroscópicos e à microscopia óptica e eletrônica foram compatíveis com o quadro de adenocarcinoma mamário de origem viral do tipo MuMTV (Murine Mammary Tumor Virus)