Ea(PV) provides a convenient, useful method to assess arterial load and its impact on the human ventricle. These results highlight effects of increased pulsatile load caused by aging or hypertension on the pressure-volume loop and indicate that this load and its effects on cardiac performance are often underestimated by mean arterial resistance but are better accounted for by Ea.
There is increasing interest in the role of T follicular helper (Tfh) cells in autoimmunity from the perspective of both their role in breach of tolerance and their effects on the natural history of disease progression. Indeed, the critical role of Tfh cells in autoimmunity is further highlighted based on their location in the germinal center (GC), a pathogenic hot spot for development of autoreactivity. To address the role of Tfh cells in primary biliary cirrhosis (PBC), we comprehensively evaluated the immunobiology of CXCR5+CD4+ Tfh cells in 69 patients with PBC, including a nested subgroup of 16 autoimmune hepatitis (AIH) and 20 healthy controls (HC), followed for one year. We report herein several key observations. Firstly, there was an increased frequency of circulating Tfh cells in patients with PBC compared to AIH (p < 0.05) and HC (p < 0.01). Second, the function of circulating Tfh cells from PBC patients, including IL-21 production (p < 0.05), the ability to promote B cell maturation and autoantibody production, were greater than HC. Third, the frequency of these cells was significantly decreased in UDCA responders compared to UDCA-treated non-responders, in both cross-sectional (p = 0.023) and longitudinal studies (p = 0.036),respectively. Indeed, similar increases of Tfh cells were noted in liver and spleen. In conclusion, these results significantly extend our understanding of lymphoid subpopulations in PBC and their relative role in disease expression. Our data also provide a novel biomarker for evaluation of the effectiveness of new therapeutic approaches.
Background and Purpose-Cerebral edema develops very early after the onset of focal cerebral ischemia and may be a major factor in early disability after an acute ischemic stroke. There have been very limited studies on the usefulness of antiedemic agents as neuroprotective agents in the setting of focal cerebral ischemia. We tested the neuroprotective effects of a new potent nonpeptide vasopressin receptor V 1 antagonist, SR-49059, in a focal embolic stroke model in rats. Methods-Focal ischemic injury was induced by embolizing a preformed clot into the middle cerebral artery (MCA).Infarction volume was measured at 48 hours after the MCA occlusion. Neurological deficits, ischemic brain edema, seizure activity, and mortality and hemorrhage rates were also documented. Results-Treatment with SR-49059 (2 mg/kg), initiated immediately after MCA occlusion, significantly reduced infarction volume (PϽ0.05) measured at 48 hours after the arterial occlusion. In animals in which the treatment was delayed for 1 hour after MCA occlusion, infarction volume was also reduced significantly (PϽ0.05). Infarction volume in the rats that received the drug at 3 or 6 hours after MCA occlusion was not different from that in the vehicle-treated group. Treatment with SR-49059, when started early after the arterial occlusion, also reduced neurological deficits and ischemic brain edema. Injection of drug at a higher dose (30 mg/kg) also reduced infarction volume and improved functional recovery but was not superior to the lower dose (2 mg/kg) when the drug was administrated at 1 hour after MCA occlusion. Conclusions-Our data show that the selective vasopressin receptor antagonist SR-49059 is a potent neuroprotective agent when used early after onset of arterial occlusion in an embolic focal ischemia model in rats. Further studies are needed in stroke models to better understand its neuroprotective properties when used alone or in combination with thrombolysis. (Stroke. 2002;33:3033-3037.)
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