RESUMO
Rod-derived cone viability factor (RdCVF) is a trophic factor of the thioredoxins family that promotes the survival of cone photoreceptors. It is encoded by the nucleoredoxin-like gene 1 Nxnl1 which also encodes by alternative splicing a long form of RdCVF (RdCVFL), a thioredoxin enzyme that interacts with TAU. The known role of thioredoxins in the defense mechanism against oxidative damage led us to examine the retinal phenotype of the Nxnl1(-/-) mice exposed to photooxidative stress. Here we found that, in contrast to wild-type mice, the rod photoreceptors of Nxnl1(-/-) mice are more sensitive to light after exposure to 1700 or 2500 lx. The delivery of RdCVF by AAV to mice deficient of Nxnl1(-/-) protects rod photoreceptors from light damage. Interestingly, the RdCVF2L protein, encoded by the paralog gene Nxnl2, is able to reduce TAU phosphorylation, as does RdCVFL, but does not protect the rod from light damage. Our result shows that the Nxnl1 gene, through the thioredoxin RdCVFL, is part of an endogenous defense mechanism against photooxidative stress that is likely of great importance for human vision.
Assuntos
Proteínas do Olho/genética , Terapia Genética/métodos , Células Fotorreceptoras Retinianas Cones/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Retinose Pigmentar/terapia , Tiorredoxinas/genética , Processamento Alternativo , Animais , Sobrevivência Celular , Dependovirus/genética , Proteínas do Olho/metabolismo , Feminino , Deleção de Genes , Técnicas de Transferência de Genes , Luz/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Oxirredução , Estresse Oxidativo , Fosforilação , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Bastonetes/patologia , Retinose Pigmentar/etiologia , Retinose Pigmentar/genética , Retinose Pigmentar/patologia , Transdução de Sinais , Tiorredoxinas/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismoRESUMO
Three groups of eight calves, naturally infected with gastrointestinal nematodes and artificially infected with Dictyocaulus viviparus were used to evaluate the efficacy of moxidectin pour-on at dose rates of 0.35 mg/kg and 0.5 mg/kg bodyweight. With both doses the efficacy was 100 per cent against adult D viviparus, Trichostrongylus axei, Ostertagia species and Nematodirus helvetianus. It was more than 99 per cent against Ostertagia and Nematodirus species fourth stage larvae. A small number of Cooperia species were found after treatment, and for this parasite, the efficacy of moxidectin ranged from 97.6 per cent against the larval stages to 98.8 per cent against the adults. No adverse reactions to the moxidectin treatment were observed.
Assuntos
Anti-Helmínticos/uso terapêutico , Doenças dos Bovinos/tratamento farmacológico , Enteropatias Parasitárias/veterinária , Pneumopatias Parasitárias/veterinária , Infecções por Nematoides/veterinária , Abomaso/parasitologia , Administração Tópica , Ração Animal/parasitologia , Animais , Anti-Helmínticos/administração & dosagem , Antibacterianos , Bovinos , Doenças dos Bovinos/sangue , Doenças dos Bovinos/parasitologia , Infecções por Dictyocaulus/sangue , Infecções por Dictyocaulus/tratamento farmacológico , Fezes/parasitologia , Enteropatias Parasitárias/sangue , Enteropatias Parasitárias/tratamento farmacológico , Intestino Delgado/parasitologia , Pulmão/parasitologia , Pneumopatias Parasitárias/sangue , Pneumopatias Parasitárias/tratamento farmacológico , Macrolídeos/administração & dosagem , Macrolídeos/uso terapêutico , Masculino , Nematoides/isolamento & purificação , Infecções por Nematoides/sangue , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/parasitologia , Contagem de Ovos de Parasitas/veterinária , Pepsinogênios/sangue , Distribuição AleatóriaAssuntos
Anti-Helmínticos/uso terapêutico , Antibacterianos/uso terapêutico , Doenças dos Bovinos/tratamento farmacológico , Infecções por Dictyocaulus/tratamento farmacológico , Ostertagíase/veterinária , Abomaso/parasitologia , Animais , Anti-Helmínticos/administração & dosagem , Antibacterianos/administração & dosagem , Bovinos , Doenças dos Bovinos/patologia , Dictyocaulus/efeitos dos fármacos , Dictyocaulus/isolamento & purificação , Infecções por Dictyocaulus/patologia , Injeções Subcutâneas/veterinária , Pulmão/parasitologia , Macrolídeos , Masculino , Ostertagia/efeitos dos fármacos , Ostertagia/isolamento & purificação , Ostertagíase/tratamento farmacológico , Ostertagíase/patologia , Distribuição AleatóriaRESUMO
The efficacy of orally administered moxidectin was determined against four benzimidazole-resistant nematode isolates. At the start of the trial, 30 lambs were each infected experimentally with 20,000 third stage larvae (5000 Haemonchus contortus, 7000 Teladorsagia circumcincta, 3000 Trichostrongylus colubriformis and 5000 Cooperia curticei); 28 days later they were allocated randomly to three groups of 10: one untreated group, one group treated orally with fenbendazole (5 mg/kg bodyweight) and one group treated orally with moxidectin (0.2 mg/kg). Samples of faeces were taken five and 10 days after treatment and the lambs were killed 10 days after treatment. Fenbendazole reduced the average number of nematode eggs in faeces by 95 per cent and the average number of worms by 25 to 45 per cent according to the species. The efficacy of moxidectin against these benzimidazole-resistant isolates was 100 per cent. No adverse reactions to either of the drugs were observed.
