Translational research : the journal of laboratory and clinical medicine
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Pulmonary vein isolation is an established therapeutic procedure for symptomatic atrial fibrillation (AF). This approach involves ablation of atrial tissue just outside the pulmonary veins. However, patient outcomes are limited because of a high rate of arrhythmia recurrence. ⋯ An innovative device that can ablate inside pulmonary veins and prevent stenosis is a viable strategy to increase long-term efficacy. We have developed a prototypical balloon catheter device capable of nonthermal pulmonary vein ablation along with elution of an antifibrotic agent intended to eliminate arrhythmogenic substrate without the risk of stenosis and have demonstrated its functionality in 4 acute canine experiments. Further optimization of this device may provide an innovative means to simultaneously ablate and prevent pulmonary vein stenosis for improved AF treatment in humans.
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T cells bearing C4d, a complement activation product (CAP), have been shown to be highly sensitive and specific as diagnostic biomarkers for systemic lupus erythematosus (SLE). T cells bearing C4d are also functionally abnormal, suggesting a role for cell-bound CAPs in lupus pathogenesis. However, the mechanism responsible for generation of T-C4d has not been determined. ⋯ In addition, SLE patient-specific signatures can be transferred in vitro to normal T cells by exposure to Ig purified from the signature donor. Complement activation does not proceed through the generation of C5b-9 (membrane attack complex) or cellular lysis, and T-C4d does not correlate with lymphopenia. In conclusion, these results suggest that patient-specific T-C4d signatures are generated by anti-T-cell autoantibodies that trigger sublytic complement activation, a previously unrecognized pathway in lupus pathogenesis.
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Mechanical ventilation (MV), using high tidal volumes (V(T)), causes lung (ventilator-induced lung injury [VILI]) and distant organ injury. Additionally, sepsis is characterized by increased oxidative stress. We tested whether MV is associated with enhanced oxidative stress in sepsis, the commonest underlying condition in clinical acute lung injury. ⋯ In this model of VILI, oxidative stress does not occur in distant organs or skeletal muscles of rodents after several hours of MV with moderate-to-high V(T), whereas protein oxidation levels were increased in the lungs of the animals. Inflammatory events were moderately expressed in skeletal muscles and lungs of the MV rats. Concomitant sepsis did not strongly affect the MV-induced effects on muscles, myocardium, or lungs in the rodents.
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We have shown that Goto-Kakizaki (GK) rats, a lean model of type 2 diabetes, develop significant cerebrovascular remodeling by the age of 18 weeks, which is characterized by increased media thickness and matrix deposition. Although early glycemic control prevents diabetes-mediated remodeling of the cerebrovasculature, whether the remodeling can be reversed is unknown. Given that angiotensin II type 1 receptor blockers reverse pathologic vascular remodeling and function independent of changes in blood pressure in other vascular beds, we hypothesized that azilsartan medoxomil, a new angiotensin II type 1 receptor blocker, is vasculoprotective by preventing and reversing cerebrovascular remodeling in diabetes. ⋯ Azilsartan treatment lowered blood glucose in diabetic animals with no effect on blood pressure. Diabetic animals exhibited lower myogenic tone, increased wall thickness, and cross-sectional area compared with control group animals, which were corrected by azilsartan treatment when started at the onset of diabetes or later after vascular remodeling is established. Azilsartan medoxomil offers preventive and therapeutic vasculoprotection in diabetes-induced cerebrovascular remodeling and myogenic dysfunction and this is independent of blood pressure.
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C-terminal agrin fragment (CAF, 22 kDa) has been shown to be a promising new rapid biomarker for kidney function. This study evaluated the influence of hemodialysis (HD) and hemodiafiltration (HDF) treatment on serum CAF concentrations in patients with end-stage renal disease (ESRD). A total of 36 patients with ESRD undergoing chronic HD/HDF treatment were enrolled (21 high-flux-HD/Fx60 membrane, 7 high-flux-HD/Elisio19H membrane, and 8 HDF/Elisio19H membrane). ⋯ In the HD/Fx60 group, the RR of CAF was significantly lower compared with cystatin C, urea, and creatinine, in which significant removal was detected (37.9 ± 14.8%, 65.0 ± 10.7%, and 56.0 ± 9.8%, respectively, P < 0.001). CAF is a new biomarker for kidney function whose serum concentration is not influenced by conventional high-flux HD using Fx60 membrane. It might therefore represent a promising dialysis-independent biomarker for evaluation of kidney function, for example, in acute kidney failure.