RESUMO
BACKGROUND: Apolipoprotein AI/apolipoprotein E (apo-AI/apo-E) ratio change and its induction in non-hepatic tissues have been reported during liver development, regeneration, and several pathophysiologic states. The clinical implication of such changes is unclear, but these could reflect recovery and/or severity of liver damage. METHODS AND RESULTS: Using RT-PCR we analysed the mRNA expression of apo-AI and apo-E in peripheral white blood cells (PWBC) of patients with different liver diseases who underwent orthotopic liver transplantation (OLT) and compared its expression with the lipid profile and liver function tests. We found that patients showed higher levels of apo-AI mRNA without detection of apo-E mRNA on PWBC at the preoperative day, compared with healthy volunteers (HV). We found an apo-AI/apo-E mRNA ratio of 2.7 during the anhepatic stage, followed by a decrease to 1.3, 0.95, and 0.55 at days 30, 60, and 90, respectively. At the last time point, the apo-AI/apo-E ratio was similar to HV. At day 3 post-OLT, the lowest levels of high-density lipoprotein (HDL)-cholesterol (17 mg/dl; P<0.05) and the highest levels of aspartate aminotransferase, total bilirubin and alkaline phosphatase (77.5 IU/l, 37.9 g/dl, 177.8 IU/l, respectively; P<0.05) were detected. CONCLUSION: These results indicate that changes of HDL-cholesterol and apo-AI/apo-E mRNA ratio could be a good indicator of liver damage and/or hepatic functional recovery post-OLT.
Assuntos
Apolipoproteína A-I/sangue , Apolipoproteínas E/sangue , Expressão Gênica , Leucócitos/metabolismo , Hepatopatias/cirurgia , Transplante de Fígado , Fígado/fisiopatologia , RNA Mensageiro/sangue , Adulto , Fosfatase Alcalina/sangue , Apolipoproteína A-I/genética , Apolipoproteínas E/genética , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Estudos de Casos e Controles , HDL-Colesterol/sangue , Feminino , Humanos , Fígado/metabolismo , Hepatopatias/sangue , Hepatopatias/fisiopatologia , Testes de Função Hepática , Regeneração Hepática , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
Because (i) changes in plasma and liver mRNA of apolipoprotein (apo) AI have been observed in patients with alcoholic liver disease, (ii) apo AI mRNA can be induced in non-hepatic tissues, and (iii) apolipoproteins expression is influenced by plasma colloid osmotic pressure (P(CO)) and viscosity (eta), we analyzed the Apo AI mRNA expression in the peripheral white blood cells (PWBC), P(CO), and eta in control volunteers (C), patients with liver cirrhosis (LC), and cirrhotic patients with superimposed alcoholic hepatitis (LC+AH). We found that apo AI mRNA is expressed in the PWBC in 20% of C and it is induced 1.5 fold in 66.6% of LC and 1.95 fold in 85% of LC+AH. A significant decrease of P(CO) in LC and LC + AH (14.8 +/- 2.4 and 16.2 +/- 2.4 mm Hg, respectively) compared to C (27.9 +/- 2 mm Hg) was observed. By contrast, eta was mildly increased from 1.7389 +/- 0.07 in C to 1.8022 +/- 0.154 in LC and 1.9030 +/- 0.177 in LC+AH. No significant correlation was found between P(CO) and eta with apo AI mRNA but with lipid profile. In conclusion, apo AI mRNA expression in PWBC is associated to liver disease severity and could be an indirect indicator of alcoholic liver damage.
Assuntos
Apolipoproteína A-I/metabolismo , Hepatite Alcoólica/metabolismo , Leucócitos/metabolismo , Cirrose Hepática/metabolismo , RNA Mensageiro/metabolismo , Adulto , Análise de Variância , Apolipoproteína A-I/genética , Análise Química do Sangue , Viscosidade Sanguínea , DNA , Primers do DNA , DNA Complementar/genética , Humanos , México , Pressão OsmóticaRESUMO
The concept of gene therapy was introduced with great promise and high expectations. However, what appeared simple in theory has not translated into practice. Despite some success in clinical trials, the research community is still facing an old problem: namely, the need for a vector that can deliver a gene to target cells without adverse events while maintaining a long-term therapeutic effect. Some of these challenges are being addressed by the development of hybrid vectors which meld two different viral systems to incorporate efficient gene delivery and large cloning capacity with site-specific integration. The two known systems that integrate genes into specific sites in mammalian genomes are the adeno-associated virus and phage integrases. Recent experiments with hybrid vectors incorporating both of these systems are encouraging. However, extensive research should be directed towards the safety and efficacy of this approach before it will be available for gene therapy.
Assuntos
Terapia Genética/métodos , Vetores Genéticos/genética , Animais , Dependovirus/genética , Vetores Genéticos/efeitos adversos , Humanos , Integrases/genética , Proteínas Virais/genéticaRESUMO
The aim of this study was to analyze the relationship of plasma colloid osmotic pressure (COP), relative viscosity (eta) and overall outcome on the expression of albumin (ALB) mRNA in peripheral white blood cells (PWBC) of cirrhotic patients with superimposed alcoholic hepatitis (LC+AH). ALB messanger was detected in PWBC by RT-nPCR in control individuals (C), patients with liver cirrhosis (LC) and LC+AH. A higher number of LC+AH patients were positive to ALB mRNA (67%), compared to C (30%) and LC (28%). COP was decreased in LC and LC+AH groups compared to C group. No statistically significant changes were detected in eta in the different populations studied. Most of the LC+AH patients positive to peripheral ALB expression (87%) had a fatal outcome, compared to survivors (25%). Such difference was not observed with the conventional liver function tests or Maddrey's discriminant function.
