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Current hemodialysis therapy modalities such as online hemodiafiltration (HDF) attempt to enhance solute removal over a wide molecular weight range through a combination of diffusion and convection. While the effects of variations of treatment modalities and conditions have been studied reasonably well, few studies have examined the efficacy of HDF to remove middle molecules in relation to the dialyzer and membrane characteristics. In this investigation, diverse high-flux dialyzers, covering a wide range of membrane permeabilities, were compared under identical in vivo conditions to assess their ability to eliminate larger uremic retention solutes (using beta2-microglobulin as a surrogate of middle molecules) without simultaneously causing excessive leakage of useful proteins such as albumin.In a prospective, crossover study, 3 ESRD patients were treated with 8 different brands of high-flux dialyzers at 4 different ultrafiltration (UF)/substitution flow rates (QS: 0, 30, 60, 90 ml/min) in post-dilution HDF mode. Thus, each patient underwent 32 treatment sessions, with a total of 96 treatment sessions conducted during the entire clinical study. Albumin and beta2-microglobulin levels were measured in both, dialysate and blood. Both, albumin and beta2-microglobulin elimination was dependent upon the permeability of the dialysis membrane as well as on the ultrafiltration/substitution flow rates applied.At the maximum UF rate of 90 ml/min, the total albumin loss (measured in the dialysate) ranged from 300 mg/4 h (for the FLX-15 GWS dialyzers) to 7,000 mg/4 h (for the BS-1.3U dialyzers). Up to 50% reduction of albumin occurred within the first 30 minutes of the dialysis treatment, and the leakage of albumin increased exponentially with increasing UF rates as well as increasing transmembrane pressure (TMP). The various dialyzers could be classified according to their UFR-dependent beta2-m reduction rates (RR), into low (50%; FLX-15 GWS, CT 150G), medium (50-70%; Polyflux 14 S, BLS 814SD, H4) and high (70%; BS-1.3U, APS 650, FX 60) removers of middle molecules. One dialyzer type (CT 150G) showed extremely low beta2-m RR and relatively high albumin losses. Most membranes, however, showed either low albumin leakage coupled with low beta2-m removal, or high beta2-m RR but at the expense of considerable albumin leakage. Only 2 membrane types approached the desired balance between high to medium beta2-m RR while simultaneously restricting the albumin leakage especially at higher filtration/substitution rates.Our investigations demonstrate that not all dialysis membranes classified as "high-flux" are comparable in their ability to specifically and efficiently remove middle molecules, or curtail the unwanted excessive leakage of essential proteins from the patient's blood. Thus, the selection of appropriate high-flux dialyzers for specific patient requirements should be based more upon clinical evaluations and analyses rather than on product specifications alone.

A reproducible standardized method for measuring capillary bleeding time (CBT) in dogs is presented. The skin was punctured at the toe from a forelimb of non-anaesthetized dogs parallel to the edge of the horny skin of the pad. Before the procedure, a cuff of a sphygmometer was placed above the antibrachium and a hyperaemie agent was applied to the shaved area. The normal CBT in non-anaesthetized dogs was 2.25 +/- 0.76 min (x +/- SD). After injection of acetylsalicylic acid (ASA) (20 mg/kg body weight), CBT was prolonged up to 25 min. Platelet aggregation in response to 10 micrograms collagen/ml was decreased in parallel after treatment with ASA.

ADP is an important in vivo mediator of platelet aggregation. The identification and estimation of a finite number of receptor sites has been made difficult by the reversible nature of the action of ADP on platelets and because ADP can be degraded by enzymes on the platelet surface. Analogues of ADP have therefore been commonly used to study the ADP receptor. We investigated the validity of using 5'-p-fluorosulfonylbenzoyl adenosine (FSBA), an affinity analogue of ADP that inhibits ADP-induced aggregation, for studying the ADP receptor on intact washed platelets. Binding of labelled FSBA, like for ADP, was saturable. Scatchard plot analyses of equilibrium binding data indicated, positive cooperativity; the apparent affinity (2.4 × 10−6) correlated well with the amount of ADP required to cause aggregation and with the value obtained from aggregation studies. However, the platelet bound FSBA was not displaceable with excess unlabelled FSBA indicating non-reversibility of ligand binding. As the minimal criteria for receptor identification (specificity, saturability and reversibility) are not fulfilled, the usage of FSBA to study the ADP receptor must be treated with caution. As FSBA is able to bind covalently to at least four polypeptides in isolated platelet membranes, a finite number of receptors cannot be postulated using FSBA. Furthermore, positive cooperativity, as indicated by the Scatchard plots, may be explained in terms of specific non-receptor binding. As the ADP receptor cannot be identified with any degree of certainty, the possibility therfore exists that the mechanism by which ADP initiates aggregation by rearrangement of platelet membrane proteins without binding to a single protein receptor.