Abstract Casearia sylvestris Sw., Salicaceae, is an important medicinal plant widely used in Brazil for the treatment of various cardiovascular disorders. This species was included as of interest by Brazilian Unified Health System. Although preclinical studies described cardiovascular protective effects and apparent absence of toxicity, no studies have evaluated its carcinogenic potential. In this study, we proposed a short-term carcinogenesis evaluation of C. sylvestris in Wistar rats, aiming to check the safety of this species to use it as proposed by Brazilian Unified Health System. C. sylvestris leaves were obtained and the crude extract was prepared by maceration from methanol/water. Wistar rats were orally treated for 12 weeks with 50, 250 or 500 mg kg−1 of crude extract or vehicle. Body weight, daily morbidity and mortality were monitored. Blood and bone marrow samples were collect for micronucleus test, comet assay and tumor markers evaluation. Vital organs were removed to macro and histopathological analyses. The crude extract did not induce mutagenic and genotoxic effects and no alterations were observed in important tumor markers. Finally, no detectable signs of injury through gross pathology or histopathological examinations were observed. Our results certify the absence of the crude extract toxicity, indicating its safety, even at prolonged exposure as proposed by Brazilian Unified Health System.

O efeito antiviral do Foscarnet (PFA) foi demonstrado anteriormente em células de cultivo infectadas com três herpesvírus bovino (BoHV). No presente estudo, investigaram-se os seus efeitos sobre a infecção e doença causadas pelo BoHV-1 e BoHV-5 em coelhos infectados experimentalmente. Coelhos inoculados com o BoHV-5 pela via intraconjuntival (IC) e tratados com o PFA (100mg/kg/dia) a partir do dia 1 pós-inoculação (pi) apresentaram uma redução nos títulos de vírus excretados entre os dias 2 e 6 pi em comparação com o grupo não-tratado; essa diferença foi significativa no dia 3 pi [F(9,108) = 2,23; P<0,03)]. Os coelhos inoculados com o BoHV-5 e tratados com o PFA apresentaram uma redução significativa nos índices de morbidade e mortalidade (95,4% [21/22] nos controles; 50% [11/22] nos tratados; [P<0,0008]). Em coelhos inoculados com o BoHV-1 pela via IC, o tratamento com o PFA resultou em redução nos títulos de vírus excretados, entre os dias 1 e 4, e 6 e 7 pi. Esses animais apresentaram um período de incubação mais curto e um curso clínico mais longo comparando-se com o grupo controle não tratado (P<0,005 e P<0,04, respectivamente). O PFA também reduziu a freqüência e severidade da doença ocular nos coelhos inoculados com o BoHV-1. Esses resultados demonstram que o PFA possui atividade frente ao BoHV-1 e BoHV-5 in vivo e são promissores para o uso desse fármaco em terapias experimentais das infecções herpéticas dos animais domésticos.

The activity of Foscarnet (PFA) against three bovine herpesviruses (BoHVs) was previously demonstrated in cell culture. Herein we evaluated the effects of PFA on the infection and disease by BoHV-1 and BoHV-5 in a rabbit model. Rabbits inoculated with BoHV-5 in the conjunctival sac (IC) and treated with PFA (100 mg/kg/day) from day 1 to 17 post-inoculation (pi) shed less virus between days 2 and 6 pi comparing to untreated controls; this difference was significant at day 3 pi [F(9,108) = 2,23; P<0.03]. The morbidity and mortality rates of rabbits inoculated with BoHV-5 IC or intranasally (IN) were also significantly reduced in PFA-treated rabbits (50%; 11/22) comparing to untreated controls (95.4%; 21/22) (P<0.0008). In rabbits inoculated IC with BoHV-1, a reduction in virus shedding was observed in PFA-treated animals between days 1 and 4 pi; 6 and 7 pi. In addition, PFA-treated rabbits presented a longer incubation period and a shorter clinical course comparing to untreated controls (P<0.005 and P<0.04, respectively). The frequency and severity of ocular signs were also reduced in the PFA-treated group. These results demonstrate that PFA is effective against BoHV-1 and BoHV-5 in vivo and open the way towards its use in experimental therapy of herpetic infections in domestic animals.

Foram utilizadas 28 aves adultas, separadas aleatoriamente em quatro grupos. Os pombos foram anestesiados com isoflurano para a realização da osteotomia diafisária transversa do úmero direito. No grupo I, a osteossíntese foi realizada associando-se dois pinos de Kirschner e polimetilmetacrilato, intramedulares; no grupo II, os pinos de Kirschner foram substituídos por pinos de Schanz; no grupo III, foram utilizados apenas dois pinos de Kirschner; e, no grupo IV, apenas dois pinos de Shanz. Os tempos médios para a consolidação óssea foram de 29±4,04 dias no grupo I; 24±5,29 dias no grupo II; 33±3,74 dias no grupo III; e 32,9±5,21 dias no grupo IV. Foi observada migração dos pinos em 42,9% dos animais do grupo I, em 0% nos do grupo II, em 85,7% nos do grupo III, e em 28,6% nos do grupo IV. Em duas aves dos grupos I, III e IV notou-se incapacidade de voar. Os resultados demonstram que a associação de dois pinos de Schanz e polimetilmetacrilato, ambos intramedulares, é um método efetivo para osteossíntese de úmero em pombos domésticos (Columba livia), proporcionando rápida consolidação óssea e mínimas complicações.

Twenty-eight adult domestic pigeons (Columba livia) were randomly divided into four groups of seven birds each. Anesthesia was performed with isoflurane and oxygen, and an osteotomy of the right humerus midshaft was performed with an electric cutter. On the sequence, one of the following treatments was chosen: group I, two Kirschner pins and polymethylmethacrylate intramedullary; group II, two Schanz pins and polymethylmethacrylate intramedullary; group III, two Kirschner pins only; and group IV, two Schanz pins only. The mean time ± standard deviation for fracture healing was 29±4.04 days in group I; 24±5.29 days in group II; 33±3.74 days in group III; 32.9±5.21 days in group IV. Pin migration was observed in 42.9% of the group I animals, 0% of group II, 85.7% of group III, and 28.6% of group IV. Two pigeons of groups I, III, and IV presented flight incapability. The results suggest that two Schanz pins and polymethylmethacrylate intramedullary are an effective method of humeral ostheosynthesis in domestic pigeons (Columba livia), resulting in faster fracture healing with minimal complications.