PubMed · 4931190
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C G Kormendy, A D Bender. 1971. Chemical interference with aging.. https://doi.org/10.1159/000211808
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BACKGROUND: We report the clinical course of a patient who developed fever, hypoxia, and bilateral pulmonary infiltrates two and a half years after orthotopic liver transplantation (OLT) for cirrhosis due to hepatitis C. The patient had a history of hepatitis C-associated vasculitis manifested by purpuric skin rashes, renal abnormalities, and elevated cryoglobulins, and was receiving interferon-alpha at the time of presentation. RESULTS: The results of bronchoscopy with bronchoalveolar lavage were unrevealing, and open lung biopsy revealed active small vessel vasculitis. The patient responded dramatically to plasmapheresis and the addition of high-dose corticosteroids with resolution of hypoxia, pulmonary infiltrates, and glomerulonephritis. This is, to our knowledge, the first report of the successful treatment of hepatitis C-associated pulmonary vasculitis after OLT. CONCLUSIONS: We conclude that hepatitis C-associated pulmonary vasculitis should be included in the differential diagnosis of a patient presenting with fever, hypoxia, and pulmonary infiltrates after OLT for hepatitis C. Treatment with plasmapheresis and high-dose corticosteroids may be effective in patients with this disorder.
Several cytokines and their receptors are identified in brain; one of these is the proinflammatory cytokine interleukin-1beta that is synthesized and released from neurons and glia in response to stress or insult. Among the actions of interleukin-1beta is its ability to inhibit long-term potentiation in the hippocampus in vitro, an action that mimics one of the consequences of stress and age. It has been shown that the concentration of interleukin-1beta in brain tissue is increased in neurodegenerative conditions, and recent evidence from our laboratory has indicated an increase in the concentration of interleukin-1beta in the hippocampus of aged rats. These observations led us to consider that the underlying common cause of impaired long-term potentiation in aged and stressed rats might be increased endogenous interleukin-1beta concentration in hippocampus. The data presented here indicate that there was an inverse relationship between concentration of interleukin-1beta in the dentate gyrus and long-term potentiation in perforant path-->granule cell synapses in aged rats, stressed rats, and rats pretreated with interleukin-1beta. The evidence suggested that the cytokine induces formation of reactive oxygen species that triggers lipid peroxidation in vivo, as well as in vitro, and that these changes lead to depletion of membrane arachidonic acid that correlates with impaired long-term potentiation. We propose that three theories of aging, the glucocorticoid theory, the membrane theory, and the free radical theory, constitute three facets of age with one underlying trigger: an increase in the endogenous concentration of interleukin-1beta in hippocampus.
Overexposure to corticosteroid hormones is harmful to hippocampal neuronal integrity, likely by perturbation of calcium homeostasis. To identify molecular mechanisms at the single-cell level, we characterized mRNA expression corresponding to voltage- and ligand-gated Ca channels in individual dissociated CA1 neurons in response to long-term corticosterone (CORT) exposure. Predominant mineralocorticoid receptor occupation (ADC-LO group) resulted in low levels of P/Q- and L-type Ca channel mRNAs, high levels of GluR-2 versus GluR-1, and a high ratio of NMDAR-2A to NMDAR-2B mRNA. Corresponding alterations in protein expression were consistent with the restriction of Ca influx. In contrast, additional glucocorticoid receptor occupation (ADC-HI group) altered the expression of these mRNAs in a manner consistent with enhanced Ca influx; interestingly, qualitatively similar alterations were seen in control ADX neurons. Electrophysiological data from the same neurons indicate that Ca current amplitudes also are modulated by CORT, although on a shorter time scale. Finally, principal components analysis (PCA) suggests that neuronal AMPA and NMDA receptor composition may be regulated by MR and GR activation in a complex manner. Therefore, our data implicate molecular events by which CORT may regulate Ca influx into CA1 hippocampal neurons.