Biomaterials, artificial cells, and immobilization biotechnology : official journal of the International Society for Artificial Cells and Immobilization Biotechnology最新文献

Isovolumic exchange transfusion (25% of total estimated blood volume) was carried out in the anesthetized dogs using 9 g/dl of unmodified human stroma-free hemoglobin solution (SFHS). The objective was to determine the systemic hemodynamic, blood distribution and renal effects of SFHS over a 2-3 hour period post-exchange. At 30 minutes after the exchange, blood pressure rose from 114 +/- 117 to 133 +/- 22 mmHg, but this rise was not sustained thereafter. Mean pulmonary arterial blood pressure rose from 8 +/- 3 to 13 +/- 2 mmHg, and remained above the pre-exchange level up to 3 hours post-exchange. Cardiac output remained within normal limits. Significant flow-increments were seen at 30 minutes in heart, brain, liver, gut, and kidney, but these were also not sustained. A fall in glomerular filtration rate (GFR) occurred after the exchange and remained below the pre-exchange level. A reduction in urine flow at 150 minutes post-exchange was observed and was accompanied by a reduction in urinary electrolyte excretion. The findings suggest that the initial effects of the administration of unmodified stroma-free hemoglobin solution are those of peripheral vasoconstriction which does not appear to significantly restrict flow to the vital organs, such as heart and brain. Unmodified hemoglobin was found to cause a decrease in renal function.

The clearance of the haemoperfusion cartridge H 200 C Tekin was determined in vitro for blood dissolved carbamazepine to test the efficiency of haemoperfusion treatment. In the first hour of in vitro haemoperfusion test of pig blood (concentration of carbamazepine 1084 mg/l) a clearance of 190 ml/min was obtained, which declined slightly to 150 ml/min after 4 hours. In a second test the elimination of carbamazepine from albumin solution was proven to be more than 1000 mg of carbamazepine after a four hour perfusion period using teflon coated charcoal. These results are in accordance with the clinical course of a 30 years old male patient who presented with severe hypoxaemia due to acute intoxication by 6 g carbamazepine. The carbamazepine blood level was 33.7 mg/l. Charcoal haemoperfusion was started immediately. A dramatic improvement of clinical symptoms was already observed during haemoperfusion. The carbamazepine serum level was 18.6 mg/l after 4 hours of haemoperfusion.

Clinical usefulness of calcium acetate (CAA) as phosphorus binder was assessed in 19 stable hemodialysis patients with persistent hyperphosphatemia. All were dialysed thrice weekly with a constant dialytic schedule and a dialysate calcium of 3.5 mEq/l. One month prior the study beginning all patients stopped assumption of Ca and vitamin D supplements. In the first period of the study CAA (mean daily doses 2.2 g) was administered for one month followed by 15 days of withdrawal. The mean serum phosphorus decreased from 7.6 +/- 1.4 to 5.8 +/- 0.8 mg% (p < 0.005). After 15 days of withdrawal mean serum phosphorus reached the pretreatment value. Then the patients entered a long term study with personalized doses of CAA (between 1 and 4 g/day) and administration in 8 of them of alpha-calcidol. After a mean follow-up period of 5.4 +/- 1.5 months serum phosphorus was reduced from 7.5 +/- 1.1 to 5.6 +/- 1.1 mg% (p < 0.0005) while calcemia increased from 9.0 +/- 0.7 to 9.6 +/- 0.6 mg% (p < 0.005). Only one patient developed mild hypercalcemia. We concluded that CAA is a safe alternative to calcium carbonate for the control of hyperphosphatemia of uraemic patients for the most efficient phosphorus binding and the lesser absorption of calcium.

Efficient removal of total body burden beta 2-Microglobulin (beta 2-M) in uremia is a continuing challenge, as dialysis-related amyloidosis represents a major complication of chronic renal replacement therapy. To investigate long-term beta 2-M removal we studied 3 groups of stable end-staged renal failure patients over a period of 4 years; we compared low flux (cuprophane) hemodialysis (n = 12), high flux (polysulfone) hemodialysis (n = 12) and hemofiltration using high flux polysulfone (n = 8). In contrast to the cuprophane membrane, the polysulfone membrane eliminated considerable amounts of beta 2-M. This was associated with a sustained reduction of predialysis serum beta 2-M-levels (by 20%). Compared with high flux hemodialysis, hemofiltration provided a 50% higher elimination of beta 2-M. Thus, our long-term evaluation of beta 2-M removal suggests that hemofiltration rather than hemodialysis may be the treatment of choice for delaying the incidence of dialysis-related amyloidosis.

A modified hemoglobin solution (- conjugate solution, PHP solution) has very interesting characteristics such as oxygen-carrying property without corpuscular components. Experimental use of the PHP solution has shown promising possibilities as a perfusate relevant to organ transplantations. 1) Elongation of warm ischemic time in canine kidneys: Dogs survived even with the unilateral kidneys which had been exposed up to 4.5 hour warm ischemia and, thereafter, perfused with the PHP solution. 2) Elongation of perfusion preservation period of canine livers: Dogs survived with the transplanted livers which had been perfused for 48 hours with the PHP solution. 3) Successful perfusion of rat small intestine: Lewis rat intestines perfused and preserved for 12 hours with the PHP solution showed a higher survival rate compared with those with Collins or UW solution. 4) Removal of antibodies: By exchange transfusion with a total of 30-60 ml of the PHP solution, a Lewis rat hematocrit lowered to 5% while IgG went down to nil from 8970 mg/dl, IgA to 28 mg/dl from 118 mg/dl and IgM to 190 mg/dl from 897 mg/dl. This technique is expected to be applicable for removal of the naturally existing antibodies in xenotransplantation.

The effects of injecting perfluorochemical (PFC) emulsions of varying concentrations on lymphoid tissues have been studied in rats. Tissue weights were increased in proportion with quantity of PFC injected, with spleen responses consistently greater than those of the liver. PFC droplets recovered from tissues had mean diameters in the 1-10 microns range, with those from the spleen being larger than from the liver. Recovered droplet diameters were considerably greater than freshly-prepared emulsion mean particle sizes (0.20-0.25 microns). This suggests that coalescence of emulsion droplets following accumulation in tissues is a pre-requisite to the eventual excretion of PFC vapour through the lungs.

The effects of pre-injection of mice with a novel perfluorodecalin-based emulsion on the responses to photodynamic therapy (PDT) using the photosensitizer, metatetra (hydroxyphenyl) porphyrin (m-THPP), have been studied. Injection of emulsion after m-THPP and before illumination (activating wavelength 648 nm) protected skin against PDT-induced inflammatory effects, as reflected by decreases (P less than 0.05) in vascular permeability and oedema formation. However, there was no protection against epidermal cell loss. In contrast, injection of emulsion before sensitizer had no corresponding effect. A fall in mean dermal temperature of up to 6 degrees C occurred in mice injected with emulsion 1-2.5 h before illumination suggesting a decrease in skin blood flow which would reduce oedema formation. Possible mechanism(s) for this apparent protective effect are discussed.

A challenging aim in developing injectable fluorocarbon emulsions is to combine good flow characteristics (especially at low shear rates) with the high fluorocarbon concentration required for high oxygen delivery or effective contrast in imaging, long shelf life, and biological acceptability. A good balance of these sometimes conflicting objectives has been achieved with 90% w/v concentrated emulsions of various fluorocarbons, including the radiopaque oxygen carrier perfluorooctylbromide (PFOB, perflubron). The sterile emulsions have viscosities of about 20 cPs at a shear rate of 1 sec-1; the viscosity decreases rapidly with fluorocarbon concentration, and at 60% w/v the viscosity is less than that of human blood. The emulsions are suitable for injection as prepared, and are stable unfrozen for over a year.

Modified hemoglobin consists of (1) encapsulated hemoglobin and (2) crosslinked hemoglobin (polyhemoglobin, intramolecularly cross-linked hemoglobin and conjugated hemoglobin). There have been new advances in all types of modified hemoglobins. Modified hemoglobins are effective in hemorrhagic shock. However, it is important to define hemorrhagic shock models and experimental designs. Important progress has been made in research on vasoactivities, organ perfusion, organ preservation, biodistribution, hematology, complement activation immunology and other areas. A preclinical screening test may bridge the gap between animal safety studies and injection into human. Potential new sources of hemoglobin included bovine hemoglobin, recombinant human hemoglobin and synthetic heme.