SummaryThe objectives of this work were the analysis of the functional characteristics of circulating monocytes and T lymphocytes in patients with liver cirrhosis, and evaluation of the relationship with an increased exposure to antigens due to bacterial translocation. Forty patients with liver cirrhosis (20 with compensated cirrhosis and 20 with ascitic decompensation) and 20 healthy control subjects were studied. Bacterial translocation was evaluated by serum levels of lipopolysaccharide binding protein (LBP). Macrophage activation was studied by CD40 antigen expression. T lymphocytes were analysed for activation (CD25 + , CD122 + ), effector function (CD8 + CD45RO + CD57 + ), apoptosis (CD95 + ) and regulatory abilities, either by analysis of the membrane expression of co-stimulatory molecules CD80, CD86 and CD28, or by quantification of regulatory T cells CD4 + CD25 high forkhead box P3 (FoxP3). The percentage of activated monocytes and T lymphocytes in patients was increased significantly. The proportions of effector senescent cells and of those near to apoptosis were also significantly higher. With respect to these proportions, there were no significant differences between patients in function of the presence or absence of decompensation or in function of the increased or normal values of LBP. Conversely, those patients with elevated levels of LBP presented a significantly higher frequency of regulatory T cells than those with normal levels. In conclusion, patients with liver cirrhosis showed an intensive activation state with a higher percentage of cells committed to activation-induced death, even in non-advanced stages. It is possible that bacterial permeability and endotoxaemia contribute to the expansion of those lymphocyte populations implicated in the prevention of a more severe antigen-induced immunopathology.
Transmission of disease to contacts was high (11%) compared with other documented outbreaks (0.7-2%). The results support recommended guidelines for contact tracing but also provide grounds to recommend, for outbreak cases, screening of casual contacts of smear-positive cases and contacts exposed to more than one case, drug users or prisoners.
Summary
Interferon (IFN)-a induced CD4+ T lymphopenia is a toxic effect of the treatment of chronic hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-co-infected patients. To increase the knowledge about this secondary effect, we performed an analysis of the evolution of the T cell receptor excision circles (TRECs), CD4+ and CD8 + T cells and of their CD45RO + and CD45RA+ subpopulations during the treatment of chronic hepatitis HCV with peginterferon alpha (pegIFN-a) + ribavirin. Twenty HCV/HIV-coinfected patients, with undetectable HIV load after highly active antiretroviral therapy (HAART), were treated with pegIFN-a + ribavirin. TRECs were determined using real-time polymerase chain reaction.
lymphocytes. A progressive decrease in both T cell populations, as well as of their CD45RO+ and CD45RA + subpopulations, was detected, with a difference between the baseline and nadir levels approaching 50%. The evolution of T cell populations and TRECs was independent of the response to the treatment. T lymphocytes and their subpopulations returned to baseline levels at 24 weeks after the end of treatment, with the exception of the T CD4 + CD45RA + subpopulation. The ratio of CD4 + CD45RO + /CD4 + CD45RA + increased from 0·89 (baseline) to 1·44 (24 weeks after the end of the therapy). TRECs/ml did not return to the basal values. In conclusion, a significant reduction of CD4 + and CD8 + T cells, and of their CD45RA + and CD45RO + subpopulations, in HIV/HCV co-infected patients treated with pegIFN-a was observed. Both subpopulations increased after the suppression of treatment, but the CD4 + CD45RA subpopulation did not reach the basal levels as a consequence, at least in part, of a decrease in thymic production.
Diazepam, at the dose studied, does not appear to reverse the chloroquine-induced membrane-stabilising effect in acute moderately severe chloroquine intoxication. Supportive intensive care of these intoxications appears to be all that is necessary.
Diazepam, at the dose studied, does not appear to reverse the chloroquine-induced membrane-stabilising effect in acute moderately severe chloroquine intoxication. Supportive intensive care of these intoxications appears to be all that is necessary.
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