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      Oral Supplementation with γ-Linolenic Acid Extracted from Mucor circinelloides Improves the Deformability of Red Blood Cells in Hemodialysis Patients

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          Background: The development of abnormalities in red blood cell (RBC) deformability in patients undergoing hemodialysis remains a major problem, because it is related to peripheral microcirculation, oxygen supply, and various complications in such patients. γ-Linolenic acid (GLA; 18:3n-6), one of the polyunsaturated fatty acids and a precursor of prostaglandin E<sub>1</sub>, is reported to have a favorable effect on the deformability of circulating blood cells in diabetic patients. Methods: In order to clarify the efficacy of GLA on RBC deformability in 7 patients undergoing maintenance hemodialysis, we examined in a pilot study the changes in the deformability of RBC and the changes in the phospholipid fatty acid composition in both plasma and RBC membrane before and after high-dose oral supplementation with GLA derived from Mucor circinelloides for 12 weeks. Results: Before supplementation, the micropore passage time of RBC suspension, which is an indicator of RBC deformability, in these patients was markedly longer than that in healthy control subjects. After administering GLA, the prolonged passage time of the patients both rapidly and steadily decreased and nearly reached control levels. Light microscopic observations of RBCs using Giemsa stain revealed a decreased number of poikilocytes after supplementation. An analysis of the fatty acid composition before treatment and 8 weeks after starting the treatment showed the dihomo-γ-linolenic acid (DGLA; 20:3n-6) level in the plasma to have increased (p < 0.05), while the arachidonic acid (AA; 20:4n-6) concentration in the RBC membrane decreased (p < 0.05). The level of DGLA in the RBC membrane, the level of GLA, and the ratio of GLA + DGLA/AA in plasma and RBC membrane did not change significantly; however, these all tended to increase. Conclusion: The results of this pilot study indicate that the oral supplementation of GLA extracted from M. circinelloides improves the poor RBC deformability in hemodialysis patients, partly by inducing changes in the composition of fatty acids in plasma and RBC membrane.

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          Modified cell-flow microchannels in a single-crystal silicon substrate and flow behavior of blood cells.

          Previously reported cell-flow microchannels in a single-crystal silicon substrate (Microvasc. Res. 44, 226-240, 1992) have been modified, and flow behavior of blood cells is described using flow rate-time curves and video pictures. The principal structure (2600 identically sized channels in parallel) was retained to give the same simple quantitative measure of the total flow rate for blood cell suspensions under constant suction. Level areas (terraces) were placed at the entrance and exit sides of the parallel channels level with the channel depth (4.5 microns) so that blood cells just entering into and flowing out of the channels could be more clearly observed under reflecting illumination. Three lengths (10, 20, and 100 microns) of channel were used each with a terrace width of 30 microns. In agreement with calculated values, the resistance to flow at the terrace portion was shown to be nearly equal to that per 10 microns of the channel portion. Clearer pictures were obtained of channel blocking by activated leukocytes and platelet aggregates after addition of each stimulant. Erythrocyte aggregates showed easy transit even through the 100-microns-long channels and through narrow spaces, including gaps probably narrower than 2 microns, which were formed between plugging leukocytes at the terrace portion.
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            Effects of Oral Supplementation with Evening Primrose Oil for Six Weeks on Plasma Essential Fatty Acids and Uremic Skin Symptoms in Hemodialysis Patients

            Abnormalities in plasma composition of essential fatty acids (EFAs) may be associated with the etiology of pruritus and other skin problems in patients undergoing hemodialysis. To study whether an oral supplementation with ω–6 (n–6) EFAs would restore deranged plasma EFAs and ameliorate skin symptoms, 9 and 7 dialysis patients were randomly assigned to receive either γ-linolenic acid (GLA)-rich evening primrose oil (EPO) or linoleic acid (LA) (2 g/day each) for 6 weeks. Plasma concentrations of EFA were analyzed by gas chromatography and uremic skin symptoms were assessed for dryness, pruritus and erythema by questionnaire and visual inspection in a double-blind manner. The patients given EPO exhibited a significant (p 1 ) with no concomitant change in plasma arachidonic acid (a precursor of pro-inflammatory prostaglandin E 2 and leukotriene B 4 ). In contrast, those given LA exhibited a significant (p < 0.05) increase in LA but not in any other n–6 EFAs, whereas they exhibited a significant (p < 0.05) decrease in plasma docosahexaenoic acid. The patients given EPO showed a significant (p < 0.05) improvement in the skin scores for the three different uremic skin symptoms over the baseline values and a trend toward a greater improvement (0.05 < p < 0.1) in pruritus scores than those given LA. Results indicate that GLA-rich EPO would be a more favorable supplemental source than LA in terms of shifting eicosanoid metabolism toward a less inflammation status through modifying plasma concentrations of their precursor n–6 EFAs. Further studies are required to confirm the efficacy and safety of EPO therapy for the treatment of uremic pruritus.
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              Reducing lipid peroxidation stress of erythrocyte membrane by alpha-tocopherol nicotinate plays an important role in improving blood rheological properties in type 2 diabetic patients with retinopathy.

              The effects of alpha-tocopherol nicotinate on blood viscoelasticity and viscosity and on lipid peroxidation stress in erythrocyte membranes in patients with Type 2 DM were investigated. Thirteen Type 2 diabetic subjects with retinopathy were given alpha-tocopherol nicotinate 300 mg tds, after meals, for 3 months. The treatment resulted in significant reductions of blood viscosity at different shear rates (e.g. -2.23 +/- 2.82 p<0.015, gamma = 1.5 s(-1)) and viscoelasticity (p<0.004); resistance of erythrocyte deformation (p<0.001) and lipid peroxidation stress in red cell membrane (malondialdehyde or MDA reduced by 0.17 +/- 0.13 nmol l(-1) p<0.005). Plasma viscosity, red cell rigidity, and HbA1c were unchanged. There were negative linear correlations between the indices of red cell deformability and the levels of MDA of red cell membrane both pre- and post-treatment (e.g. R = -0.79, p<0.001; R = -0.78, p<0.002, n = 13; pre- and post-, respectively). We suggest that the improvements of rheological properties of blood and red cell deformability by alpha-tocopherol nicotinate are mainly attributed to reducing lipid peroxidation stress on membrane of red blood cells. The treatment may be useful in slowing deterioration of microangiopathy in Type 2 DM.

                Author and article information

                S. Karger AG
                October 2000
                22 September 2000
                : 86
                : 2
                : 122-128
                aDepartment of Dermatology, Mito Saiseikai General Hospital, Mito, bDepartment of Dermatology, Institute of Clinical Medicine, University of Tsukuba, cDivision of Nephrology, Department of Internal Medicine, Tsukuba Gakuen General Hospital, Tsukuba, dKowa Technosearch Co. Ltd., Osaka, and eIdemitsu Petrochemical Co. Ltd., Tokyo, Japan
                45729 Nephron 2000;86:122–128
                © 2000 S. Karger AG, Basel

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                Figures: 3, Tables: 3, References: 20, Pages: 7
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