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      Does Bicarbonate Transfer Have Relevant Hemodynamic Consequences in Standard Hemodialysis?

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          Background: In a previous study we demonstrated that mild metabolic alkalosis resulting from standard bicarbonate hemodialysis induces hypotension. This study aimed to compare hemodynamic consequences of either a decrease in the dialysate bicarbonate from 32 to 26 mmol/l or an increase in the dialysate calcium of 0.25 mmol/l and to verify whether the calcium shift secondary to alkalemia explains the consequences on blood pressure. Methods: In this randomized controlled trial with a single-blind, cross-over design, we used dialysis liquids with two different bicarbonate (32 mmol/l in modalities A and C, and 26 mmol/l in modality B) and calcium (1.25 mmol/l in modalities A and B, and 1.50 mmol/l in modality C) concentrations, and in 27 patients, 243 dialysis sessions, compared blood pressure, heart rate and the incidence of hypotension. Results: No significant differences were seen between A and B while an increase in systolic and diastolic blood pressures and a decrease in the incidence of hypotension (10.5 vs. 1.2%, p < 0.05) were documented in C. The subgroup of patients who with A showed a lower mean systolic blood pressure received more angiotensin-converting enzyme inhibitors or angiotensin II type-1 receptor blockers (36 vs. 0%, p <0.05) and in C showed a less important increase in systolic and diastolic pressures, but the incidence of hypotensive episodes between A and B was not significantly different (9.1 vs. 15.1%). Conclusions: In the present study it was not possible to demonstrate hemo dynamic instability associated with mild metabolic alkalosis. Even in the subgroup showing a lower blood pressure with a higher dialysate bicarbonate, significant hemodynamic or clinical consequences were not noticed. The calcium shift (0.05 mmol/l) related to alkalemia would justify a mean decrease in systolic blood pressure of only about 1 mm Hg.

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          Most cited references 13

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          Ezrin has a COOH-terminal actin-binding site that is conserved in the ezrin protein family

          Ezrin, previously also known as cytovillin, p81, and 80K, is a cytoplasmic protein enriched in microvilli and other cell surface structures. Ezrin is postulated to have a membrane-cytoskeleton linker role. Recent findings have also revealed that the NH2-terminal domain of ezrin is associated with the plasma membrane and the COOH-terminal domain with the cytoskeleton (Algrain, M., O. Turunen, A. Vaheri, D. Louvard, and M. Arpin. 1993. J. Cell Biol. 120: 129-139). Using bacterially expressed fragments of ezrin we now demonstrate that ezrin has an actin-binding capability. We used glutathione-S-transferase fusion proteins of truncated ezrin in affinity chromatography to bind actin from the cell extract or purified rabbit muscle actin. We detected a binding site for filamentous actin that was localized to the COOH-terminal 34 amino acids of ezrin. No binding of monomeric actin was detected in the assay. The region corresponding to the COOH- terminal actin-binding site in ezrin is highly conserved in moesin, actin-capping protein radixin and EM10 protein of E. multilocularis, but not in merlin/schwannomin. Consequently, this site is a potential actin-binding site also in the other members of the protein family. Furthermore, the actin-binding site in ezrin shows sequence homology to the actin-binding site in the COOH terminus of the beta subunit of the actin-capping protein CapZ and one of the potential actin-binding sites in myosin heavy chain. The actin-binding capability of ezrin supports its proposed role as a membrane-cytoskeleton linker.
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            Rho- and Rac-dependent Assembly of Focal Adhesion Complexes and Actin Filaments in Permeabilized Fibroblasts: An Essential Role for Ezrin/Radixin/Moesin Proteins

            The small GTPases Rho and Rac regulate actin filament assembly and the formation of integrin adhesion complexes to produce stress fibers and lamellipodia, respectively, in mammalian cells. Although numerous candidate effectors that might mediate these responses have been identified using the yeast two-hybrid and affinity purification techniques, their cellular roles remain unclear. We now describe a biological assay that allows components of the Rho and Rac signaling pathways to be identified. Permeabilization of serum-starved Swiss 3T3 cells with digitonin in the presence of guanosine 5′-O-(3-thiotriphosphate) (GTPγS) induces both actin filament and focal adhesion complex assembly through activation of endogenous Rho and Rac. These responses are lost when GTPγS is added 6 min after permeabilization, but can be reconstituted using concentrated cytosolic extracts. We have achieved a 10,000-fold purification of the activity present in pig brain cytosol and protein sequence analysis shows it to contain moesin. Using recombinant proteins, we show that moesin and its close relatives ezrin and radixin can reconstitute stress fiber assembly, cortical actin polymerization and focal complex formation in response to activation of Rho and Rac.
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              Citrate anticoagulation in continuous venovenous hemodiafiltration: a metabolic challenge.

              Feasibility and safety evaluation of regional citrate anticoagulation (RCA) versus systemic heparinization for continuous venovenous hemodiafiltration. Combined retrospective and prospective observational study performed in a secondary multidisciplinary intensive care unit of the Ospedale Civico Lugano Switzerland. Twelve hemodynamically unstable patients (median APACHE II score 26, interquartile range 22-29) in whom heparin was judged to be at least temporarily contraindicated. A switch from RCA (predilution setting; same iso-osmotic replacement and dialysis fluid) to heparinization or vice versa was recommended for the final evaluation; 56 dialyzers were used for RCA (1,400 h) and 39 for heparinization (1,271 h). Median dialyzer life span was 24.2 h (interquartile range 17.4-42.3) for RCA and 42.5 h (20.6-69.1) for heparinization. Fluid control and dialysis quality were similar in the two groups and required no additional intervention. The risk of significant hypocalcemia and metabolic alkalosis was higher at the beginning of the RCA program and decreased with the further training of the staff. Seven bleeding episodes occurred with heparinization vs. three in RCA. RCA may be a safe and useful form of anticoagulation which is more expensive than heparinization but helps to minimize bleeding risk. The risk of metabolic complications is higher at the beginning of a new RCA program. For centers lacking experienced staff we suggest reserving this technique for patients with rapid clotting of the extracorporeal circuit if treated without anticoagulation.

                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                August 2005
                25 August 2005
                : 23
                : 5
                : 365-372
                Departments of aNephrology and bInternal Medicine, Ospedale la Carità, Locarno, and cDepartment of Internal Medicine, Ospedale San Giovanni, Bellinzona, Switzerland
                87193 Blood Purif 2005;23:365–372
                © 2005 S. Karger AG, Basel

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                Page count
                Figures: 2, Tables: 5, References: 25, Pages: 8
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                Original Paper

                Cardiovascular Medicine, Nephrology

                Hemodialysis, Calcium, Alkalosis, Hemodynamics, Bicarbonate, Hypotension


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