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Arthritis and rheumatism · May 2010
Anti-citrullinated protein antibodies bind surface-expressed citrullinated Grp78 on monocyte/macrophages and stimulate tumor necrosis factor alpha production.
Anti-citrullinated protein antibodies (ACPAs), which are the most specific autoantibody marker in patients with rheumatoid arthritis (RA), correlate with disease activity; however, the role of ACPAs in RA pathogenesis has not been elucidated. We hypothesized that ACPAs may directly stimulate mononuclear cells to produce inflammatory cytokines. Thus, we identified cognate antigens of ACPAs on monocyte/macrophages and examined their immunopathologic roles in the pathogenesis of RA. ⋯ We clearly demonstrated that ACPAs enhance NF-kappaB activity and TNFalpha production in monocyte/macrophages via binding to surface-expressed citrullinated Grp78.
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Pacing Clin Electrophysiol · Jan 2007
Comparative StudyAAIsafeR limits ventricular pacing in unselected patients.
Dedicated pacing modes, such as AAIsafeR, prevent ventricular (V) pacing in selected patients. We report our experience in consecutive unselected patients. ⋯ In unselected pacemaker recipients, AAIsafeR reliably prevented V pacing compared with other pacing modes. No adverse effects were reported by any patient. Furthermore, maintaining spontaneous AV conduction protected the patients against ELT episodes.
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Continuous estimates of dynamic cerebral autoregulation during transient hypocapnia and hypercapnia.
Dynamic cerebral autoregulation (CA) is the transient response of cerebral blood flow (CBF) to rapid blood pressure changes: it improves in hypocapnia and becomes impaired during hypercapnia. Batch-processing techniques have mostly been used to measure CA, providing a single estimate for an entire recording. A new approach to increase the temporal resolution of dynamic CA parameters was applied to transient hypercapnia and hypocapnia to describe the time-varying properties of dynamic CA during these conditions. ⋯ Hyperventilation led to a marked decrease in ET(CO(2)) (-7.2 +/- 4.1 mmHg, P < 0.001). Unexpectedly, CA efficiency dropped significantly with the inception of the metronome-controlled hyperventilation, but, after approximately 30 s, the ARI increased gradually to show a maximum change of 5.7 +/- 2.9 and 5.3 +/- 3.0 for the right and left MCA, respectively (P < 0.001). These results confirm the potential of continuous estimates of dynamic CA to improve our understanding of human cerebrovascular physiology and represent a promising new approach to improve the sensitivity of clinical applications of dynamic CA modeling.
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In addition to analgesia, opioids produce opioid-induced hyperalgesia (OIH) and neuroplasticity characterized by prolongation of inflammatory-mediator-induced hyperalgesia (hyperalgesic priming). We evaluated the hypothesis that hyperalgesia and priming induced by opioids are mediated by similar nociceptor mechanisms. In male rats, we first evaluated the role of nociceptor Toll-like receptor 4 (TLR4) in OIH and priming induced by systemic low-dose morphine (LDM, 0.03 mg/kg). ⋯ OIH produced by systemic LDM is mediated by isolectin B4-positive (IB4+) and peptidergic nociceptors, whereas priming is dependent on a different class of nociceptors. Priming induced by systemic HDM is, however, mediated by both IB4+ and peptidergic nociceptors. Our findings may provide useful information for the use of low-dose opioids combined with nonopioid analgesics to treat pain and opioid use disorders.
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To examine the risk of serious infection conveyed by tumour necrosis factor α (TNFα) inhibitors in the treatment of rheumatoid arthritis (RA). ⋯ Reasons for the decline in infection rates observed at the group level were identified. The results enable expected infection rates to be calculated in individual patients based on their risk profiles.