Based upon analogy to vascular smooth muscle cells (VSMC), there are at least two putative mesangial KATP that most likely represent hetero-octamers, comprised of either rSUR2B or mcSUR2 in complex with Kir6.1. Our results define the mesangial SUR2B as the possible first link in a chain of cellular events that culminates in MC contraction and altered extracellular matrix metabolism following exposure to sulfonylureas. In addition, our results serve as the basis for the future elucidation of the electrophysiologic characteristics of the mesangial KATP and the study of endogenous regulators of mesangial cell contractility.
The effects of different dialyzer processing methods and of reuse on complement activation and dialyzer-related symptoms were studied in 96 maintenance hemodialysis patients. New dialyzers were either unprocessed (Group 1) or machine-washed with bleach and stored in formaldehyde (Group 2). Reused dialyzers were manually cleansed using the combination of bleach and formaldehyde (Group 3), or machine-washed in formaldehyde (Group 4) or peracetic acid (Group 5). Prewashed new dialyzers (Group 2) were associated with greater complement activation during dialysis when compared with unprocessed, new dialyzers (Group 1) (p less than 0.05). Reused, unbleached but formaldehyde-treated or peracetic acid-treated dialyzers (Groups 4 and 5) were associated with reduced complement activation (p less than 0.05). Complement activation was not reduced when bleach was used for reprocessing (Group 3). The percentage of patients without symptoms during dialysis was significantly greater with reused dialyzers than with new dialyzers (Groups 3 through 5 versus Groups 1 and 2; 39 versus 25%; p = 0.035). The severity of total symptoms correlated significantly (p = 0.0004) with complement activation. Our results suggest that total symptoms during dialysis are correlated with the degree of complement activation. However, trends in the data pertaining to chest pain suggest that factors other than complement activation may be important in the pathogenesis of some dialyzer-related symptoms.
Although monitoring of vascular accesses by physical examination is nearly as sensitive as surveillance measurements by vascular access pressure when performed by examiners, the frequency of examinations is limited by time. We developed intravascular access pressure surveillance as a surrogate to physical examination. Using real-time data from hemodialysis machines, we derived intravascular access pressure ratios for each dialytic procedure. An automated, noninvasive surveillance algorithm that generated a "warning" list of patients at risk for thrombosis was formulated. We hypothesized that this algorithm would reduce access thrombosis frequency. We designed a study comparing thrombosis rates during a baseline 6-month interval to three subsequent 6-month periods of active surveillance. Referrals for interventions during this 18-month period were based on persistently abnormal elevated vascular access pressure ratio tests (VAPRT) >0.55. Thrombosis rates declined progressively for arteriovenous grafts (AVG) during the intervention period compared with the baseline period. Arteriovenous fistula (AVF) thrombosis rates decreased during postintervention months 13-18 during employment of the VAPRT. We conclude that use of VAPRT can reduce thrombosis rates in vascular accesses, and the magnitude of the effect is larger and more consistent in arteriovenous grafts (AVGs) than autologous AVFs.
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