BackgroundIn this study, we investigated the mechanism of platelet activation in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), as well as the activation of the alternative complement pathway by platelets in AAV.MethodsCD62P and platelet-leukocyte aggregates in AAV patients were tested by flow cytometry. Platelets were stimulated by plasma from active AAV patients. The effect of the thrombin-protease-activated receptors (PARs) pathway was evaluated by blocking thrombin or PAR1 antagonists. After platelets were activated by plasma from AAV patients, Ca/Mg-Tyrode’s buffer and Mg-EGTA buffer were used to measure complement activation in liquid phase and on the surface of platelets.ResultsThe levels of CD62P-expressing platelets and platelet-leukocyte aggregates were significantly higher in active AAV patients than those in remission and normal controls. Platelets were activated by plasma from active AAV patients (percentage of CD62P-expressing platelets, 97.7 ± 3% vs. 1 ± 0.2%, p < 0.0001, compared with those incubated with healthy donor plasma), and this was inhibited by thrombin or PAR1 antagonists (percentage of CD62P-expressing platelets, 97.7 ± 3% vs. 2.7 ± 1%, p < 0.0001, 97.7 ± 3% vs. 5 ± 1.4%, p < 0.0001, respectively). Platelets activated by plasma from AAV patients could trigger complement activation via the alternative pathway, as demonstrated by significant elevation of C3a, C5a, and sC5b-9 and significantly more C3c and C5b-9 deposition on the surface of platelets.ConclusionsPlatelets were activated in AAV patients, and such activation was at least partially attributed to the thrombin-PARs pathway. Activated platelets triggered the alternative complement pathway in AAV.
Objective The biological functions of the platelets contributing to ANCA-associated vasculitis (AAV) are largely unclear. The current study aimed to investigate the potential role of platelet-derived microparticles (PMPs) in AAV. Methods In the current study, microparticles in AAV patients were analysed by flow cytometry, and PMPs were probed for relative levels of 640 bioactive proteins secreted from patients’ platelets using antibody microarrays. These data were then correlated with clinical and pathological parameters. Results PMPs were significantly increased in 69 AAV patients, predominantly MPO-ANCA positive patients in active stage compared with in remission [4406.8/μl (2135.4, 5485.0) vs 549.7/μl (350, 708.5), P < 0.0001], and 43% of microparticles in active AAV were PMPs. Compared with 15 patients in remission, highly expressed proinflammatory molecules in the microparticles from platelets in 15 AAV patients in active stage revealed that potential functions of PMPs were promotion of the effect of chemotaxis, adhesion, growth and apoptosis (all the patients for array analysis were MPO-ANCA positive). The level of PMPs had a significant association with disease activity, inflammation, and renal damage. Conclusion PMPs may serve as inflammatory propagators through their wide production of proinflammatory cytokines in AAV, potentially providing a novel therapeutic target.
BackgroundA previous study showed that foot stimulation can delay the bladder filling sensation and increase bladder volume in healthy humans without OAB. The aim of this study was to determine whether or not electrical stimulation of somatic afferent nerves in the foot can increase bladder capacity in neurogenic bladder patients after sigmoid cystoplasty.MethodsEleven subjects underwent 30-min foot stimulation using skin surface electrodes connected to a bladder-pelvic stimulator. The electrodes were attached to the bottom of the foot. The subjects completed a 5-day voiding diary, during which time foot stimulation was applied on day 3. The stimulation parameter was a continuous, bi-polar square wave form with a pulse duration of 200 μs and a stimulation frequency of 5 Hz. The stimulation intensity was set by each subject at a maximal level without causing discomfort.ResultsThe volume per clean intermittent catheterization (CIC) was 279.4 ± 11.7 ml and 285.4 ± 11.8 ml on the 1st and 2nd days, respectively. On the 3rd day, the average volume per CIC increased to 361.1 ± 18.1 ml after stimulation (p <0.05). The average volume per CIC returned to 295.4 ± 13.4 ml and 275.1 ± 11.5 ml on the 4th and 5th days, respectively.ConclusionsFoot stimulation can delay the bladder filling sensation and significantly increase bladder capacity in neurogenic bladder patients after sigmoid cystoplasty.
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