The combination of atorvastatin and ethanol is not more hepatotoxic to rats than the administration of each drug alone.

Animal studies and premarketing clinical trials have revealed hepatotoxicity of statins, primarily minor elevations in serum alanine aminotransferase levels. The combined chronic use of medicines and eventual ethanol abuse are common and may present a synergistic action regarding liver injury. Our objective was to study the effect of the chronic use of atorvastatin associated with acute ethanol administration on the liver in a rat model. One group of rats was treated daily for 5 days a week for 2 months with 0.8 mg/kg atorvastatin by gavage. At the end of the treatment the livers were perfused with 72 mM ethanol for 60 min. Control groups (at least 4 animals in each group) consisted of a group of 2-month-old male Wistar EPM-1 rats exposed to 10% ethanol (v/v) ad libitum replacing water for 2 months, followed by perfusion of the liver with 61 nM atorvastatin for 60 min, and a group of animals without chronic ethanol treatment whose livers were perfused with atorvastatin and/or ethanol. The combination of atorvastatin with ethanol did not increase the release of injury marker enzymes (alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase) from the liver and no change in liver function markers (bromosulfophthalein clearance, and oxygen consumption) was observed. Our results suggest that the combination of atorvastatin with ethanol is not more hepatotoxic than the separate use of each substance.

Comparison of CVI and HVT vaccine strains replication in feather tips in different Marek´s disease vaccination programs / Comparação da replicação da estirpe vacinal CVI e HVT no folículo da pena em diferentes programas vacinais para a doença de Marek

Marek's disease is an important neoplastic disease in birds caused by a serotype 1 specific herpesvirus; it is controlled by vaccination. In commercial breeders and layers in Brazil, current vaccination programs use the combination of attenuated or non-pathogenic strains of the HVT virus (turkey herpesvirus - serotype 3) and CVI 988 (Rispens - serotype 1). The combination of serotype 3 and 1 it has been an important and effective control strategy through the vaccination of long-lived birds. In addition, more recently the recombinant rHVT strain (vectorized vaccines) has been used in some vaccine programs. This studys main objective was to compare CVI and HVT components replication in feather tips in three different Marek's disease (MD) immunoprophylactic programs (T01 program A, T02 program B and T03 program C). Quantification of these two vaccine strains was performed by real-time PCR in samples collected at the ages of 14, 21, and 28 days. At 14 days, mean of log[cvi] in program B was significantly higher than C (p<0.05). For mean of log[hvt], at 28 days, program B was significantly higher than A (p<0.05). For proportion of positives, at 14 days, program B had 2.7 times more risk to be positive in CVI than program C (p<0.001). At 21 days, program B had 1.7 times more risk to be positive in CVI than program C (p=0.005). For HVT, at 28 days, program B had 3.2 times more risk to be positive than program A (p=0,009). Results showed significant differences between the treatments evaluated. In general the conventional combination Mareks vaccine containing CVI+HVT (program B) showed higher replication rate and percentage of vaccine coverage than the programs with rHVT vector vaccines (program A and C).(AU)

A doença de Marek é uma importante doença neoplásica das aves causada por um herpesvírus específico do sorotipo 1 e seu controle se faz por vacinação. Em reprodutoras e poedeiras comerciais do Brasil, os programas de vacinação utilizam a combinação de estirpes atenuadas ou não patogênicas do vírus HVT (turkey herpesvirus - sorotipo 3) e CVI 988 (Rispens - sorotipo 1). A combinação do sorotipo 3 e 1 tem sido uma importante e efetiva estratégia de controle para aves de vida longa. Além disso, mais recentemente a fração rHVT recombinante (vacinas vetorizadas) vem sendo utilizada em alguns programas vacinais. O objetivo deste estudo foi comparar a replicação das frações CVI e HVT no folículo da pena em três programas imunoprofiláticos distintos (T01 programa A, T02 programa B e T03 programa C). A quantificação das duas estirpes vacinais foi realizada por PCR em tempo real nas amostras colhidas nas idades de 14, 21 e 28 dias. Aos 14 dias, em média, log[cvi] do programa B foi significativamente maior do que C (p<0.05). Aos 21 e 28 dias, a média do log[cvi] do programa C foi significativamente menor do que A e B (p<0.05). Para log[hvt], aos 28 dias, a média do programa B foi significativamente maior do que A (p<0.05). Para proporção de positivos, aos 14 dias, o programa B teve 2,7 vezes mais risco de ter positivos no CVI do que C (p<0.001). Aos 21 dias, o programa B teve 1,7 vezes mais risco de ter positivos no CVI do que C (p=0.005). Para HVT, aos 28 dias, o programa B teve 3,2 vezes mais risco de ter positivos do que A (p=0,009). Os resultados obtidos evidenciam diferenças significativas entre os tratamentos. De maneira geral a vacina convencional de Marek combinada com o CVI e HVT (programa B) apresentou maior taxa de replicação, velocidade e percentual de cobertura vacinal do que os programas compostos com vacinas vetorizadas com rHVT (programa A e C).(AU)

Comparison of CVI and HVT vaccine strains replication in feather tips in different Marek´s disease vaccination programs / Comparação da replicação da estirpe vacinal CVI e HVT no folículo da pena em diferentes programas vacinais para a doença de Marek

Marek's disease is an important neoplastic disease in birds caused by a serotype 1 specific herpesvirus; it is controlled by vaccination. In commercial breeders and layers in Brazil, current vaccination programs use the combination of attenuated or non-pathogenic strains of the HVT virus (turkey herpesvirus - serotype 3) and CVI 988 (Rispens - serotype 1). The combination of serotype 3 and 1 it has been an important and effective control strategy through the vaccination of long-lived birds. In addition, more recently the recombinant rHVT strain (vectorized vaccines) has been used in some vaccine programs. This study’s main objective was to compare CVI and HVT components’ replication in feather tips in three different Marek's disease (MD) immunoprophylactic programs (T01 – program A, T02 – program B and T03 – program C). Quantification of these two vaccine strains was performed by real-time PCR in samples collected at the ages of 14, 21, and 28 days. At 14 days, mean of log[cvi] in program B was significantly higher than C (p<0.05). For mean of log[hvt], at 28 days, program B was significantly higher than A (p<0.05). For proportion of positives, at 14 days, program B had 2.7 times more risk to be positive in CVI than program C (p<0.001). At 21 days, program B had 1.7 times more risk to be positive in CVI than program C (p=0.005). For HVT, at 28 days, program B had 3.2 times more risk to be positive than program A (p=0,009). Results showed significant differences between the treatments evaluated. In general the conventional combination Marek’s vaccine containing CVI+HVT (program B) showed higher replication rate and percentage of vaccine coverage than the programs with rHVT vector vaccines (program A and C).

A doença de Marek é uma importante doença neoplásica das aves causada por um herpesvírus específico do sorotipo 1 e seu controle se faz por vacinação. Em reprodutoras e poedeiras comerciais do Brasil, os programas de vacinação utilizam a combinação de estirpes atenuadas ou não patogênicas do vírus HVT (turkey herpesvirus - sorotipo 3) e CVI 988 (Rispens - sorotipo 1). A combinação do sorotipo 3 e 1 tem sido uma importante e efetiva estratégia de controle para aves de vida longa. Além disso, mais recentemente a fração rHVT recombinante (vacinas vetorizadas) vem sendo utilizada em alguns programas vacinais. O objetivo deste estudo foi comparar a replicação das frações CVI e HVT no folículo da pena em três programas imunoprofiláticos distintos (T01 – programa A, T02 – programa B e T03 – programa C). A quantificação das duas estirpes vacinais foi realizada por PCR em tempo real nas amostras colhidas nas idades de 14, 21 e 28 dias. Aos 14 dias, em média, log[cvi] do programa B foi significativamente maior do que C (p<0.05). Aos 21 e 28 dias, a média do log[cvi] do programa C foi significativamente menor do que A e B (p<0.05). Para log[hvt], aos 28 dias, a média do programa B foi significativamente maior do que A (p<0.05). Para proporção de positivos, aos 14 dias, o programa B teve 2,7 vezes mais risco de ter positivos no CVI do que C (p<0.001). Aos 21 dias, o programa B teve 1,7 vezes mais risco de ter positivos no CVI do que C (p=0.005). Para HVT, aos 28 dias, o programa B teve 3,2 vezes mais risco de ter positivos do que A (p=0,009). Os resultados obtidos evidenciam diferenças significativas entre os tratamentos. De maneira geral a vacina convencional de Marek combinada com o CVI e HVT (programa B) apresentou maior taxa de replicação, velocidade e percentual de cobertura vacinal do que os programas compostos com vacinas vetorizadas com rHVT (programa A e C).

The combination of atorvastatin and ethanol is not more hepatotoxic to rats than the administration of each drug alone

Animal studies and premarketing clinical trials have revealed hepatotoxicity of statins, primarily minor elevations in serum alanine aminotransferase levels. The combined chronic use of medicines and eventual ethanol abuse are common and may present a synergistic action regarding liver injury. Our objective was to study the effect of the chronic use of atorvastatin associated with acute ethanol administration on the liver in a rat model. One group of rats was treated daily for 5 days a week for 2 months with 0.8 mg/kg atorvastatin by gavage. At the end of the treatment the livers were perfused with 72 mM ethanol for 60 min. Control groups (at least 4 animals in each group) consisted of a group of 2-month-old male Wistar EPM-1 rats exposed to 10 percent ethanol (v/v) ad libitum replacing water for 2 months, followed by perfusion of the liver with 61 nM atorvastatin for 60 min, and a group of animals without chronic ethanol treatment whose livers were perfused with atorvastatin and/or ethanol. The combination of atorvastatin with ethanol did not increase the release of injury marker enzymes (alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase) from the liver and no change in liver function markers (bromosulfophthalein clearance, and oxygen consumption) was observed. Our results suggest that the combination of atorvastatin with ethanol is not more hepatotoxic than the separate use of each substance.