Massive Blood Transfusion in Patients with Ruptured Abdominal Aortic Aneurysm.

OBJECTIVES: The aim was to study blood transfusions and blood product ratios in massively transfused patients treated for ruptured abdominal aortic aneurysms (rAAAs). METHODS: This was a registry based cohort study of rAAA patients repaired at three major vascular centres between 2008 and 2013. Data were collected from the Swedish Vascular Registry, hospitals medical records, and local transfusion registries. The transfusion data were analysed for the first 24 h of treatment. Massive transfusion (MT) was defined as 4 or more units of red blood cell (RBC) transfused within 1 h, or 10 or more RBC units within 24 h. Logistic regression was used to calculate the odds ratio of 30 day mortality associated with the ratios of blood products and timing of first units of platelets (PLTs) and fresh frozen plasma (FFP) transfused. RESULTS: Three hundred sixty nine rAAA patients were included: 80% men; 173 endovascular aneurysm repairs (EVARs) and 196 open repairs (ORs) with median RBC transfusion 8 units (Q1-Q3, 4-14) and 14 units (Q1-Q3, 8-28), respectively. A total of 261 (71%) patients required MT. EVAR patients with MT (n = 96) required less transfusion than OR patients (n = 165): median RBC 10 units (Q1-Q3, 6-16.5) vs. 15 units (Q1-Q3, 9-26) (p = .002), FFP 6 units (Q1-Q3, 2-14.5) vs. 13 units (Q1-Q3, 7-24) (p < .001), and PLT 0 units (Q1-Q3, 0-2) vs. 2 units (Q1-Q3, 0-4) (p = .01). Median blood product ratios in MT patients were FFP/RBC (EVAR group 0.59 [0.33-0.86], OR group 0.84 [0.67-1.2]; p < .001], and PLT/RBC (EVAR 0 [0-0.17], OR 0.12 (0-0.18); p < .001]. In patients repaired by OR a FFP/RBC ratio close to 1 was associated with reduced 30 day mortality (p = .003). The median PLT/RBC ratio was higher during the later part of the study period (p < .001, median test), whereas there was no significant difference in median FFP/RBC ratio (p = .101, median test). CONCLUSION: The majority of rAAA patients undergoing EVAR required MT. EVAR patients treated with MT had lower FFP/RBC and PLT/RBC ratios than OR patients with MT. The mortality risk was lower with FFP/RBC ratio close to 1:1 in open repaired patients requiring MT. The 24 h PLT/RBC ratio increased over the study period.

Prevention of renal failure in rats receiving cis-diamminedichloroplatinum(II) by administration of furosemide.

The clinicopathological signs of renal failure induced in rats by weekly i.v. administration of cis-diamminedichloroplatinum(II) were prevented by pretreatment with furosemide. Weight loss, anemia, and generalized toxic effects of the drug were not effected by furosemide.

Acyl chain interactions and the modulation of phase changes in glycerolipids.

Fluorescence polarization measurements with 1,6-diphenyl-1,3,5-hexatriene and differential scanning calorimetry (DSC) were used to monitor phase transitions and order in the liquid state in sonicated dispersions of mono-, di- and triacylglycerols. Residual order in melted glycerolipids was indicated when the structural order parameter, S, assumed non-zero values at temperatures, t greater than or equal to tf, the DSC-determined fusion temperature. Residual order was observed with cis unsaturated di- and triacylglycerols but not with corresponding trans unsaturated or with saturated compounds. The reduced fluidity was attributed to adjacent binding of fatty acids to the glycerol molecule and the resulting interactions between fatty acyl moieties and packing effects. Lipids were considered as in an isotropic liquid or highly fluid state when diphenylhexatriene fluorescence anisotropy, rs, was equal to or less than 0.08, corresponding to S = 0. Temperatures, t0.08, for transition from the fluid state upon cooling were noted when rs = 0.08, and delta t = t0.08-tf was then taken as a measure of residual order. Tri-, 1,2-di and 1,3-dioleoylglycerol delta t values were 75, 60.9 and 13.6 degrees C, respectively. Tri-, 1,3-di- and monolinoleoylglycerol delta t values were 86, 30 and 41 degrees C, respectively. Restrictions in mobility when observed are attributable to interactions between adjacent acyl chains. Double bond location in the hydrocarbon chain affected ordering in the liquid state as simple triacylglycerol esters of cis 18:1 delta 6, trans 18:1 delta 6 and cis 24:1 delta 15 exhibited t = 37, 14 and 18 degrees C, respectively.

Fluorescence polarization order parameters and phase transitions in lipids and lipoproteins.

Fluorescence polarization measurements with 1,6-diphenyl-1,3,5-hexatriene (DPH) were used to monitor phase changes in sonicated dispersions of triacylglycerols, cholesteryl esters and phospholipids. Lipid transitions to a fluid state were detected in a novel way by noting the temperature, t0.08, at which rs, the steady state anisotropy, was equal to 0.08. According to published equations (Van Blitterswijk , W.J., Van Hoeven , R.P. and Van der Meer , B.W. (1981) Biochim. Biophys. Acta 644, 323-332), this value for rs corresponds to a value of zero for S, a structural order parameter. Saturated and trans monounsaturated fatty triacylglycerols and distearoylphosphatidylcholine yielded t0.08 values in close agreement with transition temperatures found by differential scanning calorimetry (DSC), whereas cis unsaturated triacylglycerols displayed residual anisotropy, rs greater than 0.08, at temperatures above the DSC transition. The bent configuration of the cis double-bonded fatty acyl chains probably limits freedom of movement even in the liquid state when three such chains are bound to the glycerol molecule. Cholesteryl esters of 14:0, 18:0 and cis 18:1 fatty acids all showed rs greater than 0.08 above the DSC melting point. The difference in rotational freedom of DPH in triacylglycerol and cholesteryl esters even in the 'liquid' state explains the low t0.08 in the more fluid plasma VLDL and the contrastingly high t0.08 in plasma LDL, and HDL, which contain more cholesteryl ester an less triacylglycerol.

Fatty acid modification of membrane fluidity in Chinese hamster ovary (TR715-19) cells.

Dietary saturated fatty acids, especially lauric (12:0), myristic (14:0) and palmitic (16:0) acids, which are hypercholesterolemic, influence cell membrane fatty acid composition and affect LDL receptor function. When membrane phospholipid fatty acids in Chinese hamster ovary cells, containing the human LDL receptor, were modified (Hannah J. S. et al., 1995 Metabolism 44, 1428-1434), LDL receptor function was affected, but correlations with DPH-determined membrane fluidity were weak. The role of fluidity in various membrane domains with respect to the LDL receptor is examined here. Membrane fluidity was assessed by measuring steady-state fluorescence polarization of diphenylhexatriene (DPH) and its polar propionic acid (DPH-PA) and trimethylammonium (TMA-DPH) derivatives from 38 to 4 degrees C in fatty acid modified Chinese hamster ovary cells. Fatty acid changes modulated mid-bilayer fluidity as determined with DPH, but fluidity in phospholipid headgroup domains, assessed with DPH-PA and TMA-DPH, was independent of fatty acyl composition. The DPH fluidity was related to membrane unsaturation (P < 0.02), oleate contents (P < 0.009) in particular, but inversely related (P < 0.0002) to the longer chain (> or = 20 C atoms) unsaturated fatty acids with from four to six double bonds. The LDL binding was independent of fluidity, but there were weak relations between LDL internalization and DPH-PA anisotropy and between LDL degradation and TMA-DPH anisotropy. It was concluded that LDL binding was not related to mid-bilayer fluidity, but the results with the polar probes suggest a role of fluidity in modulating vertical displacement of the LDL/LDL receptor complex across the plasma membrane.

Effects of omega 3 fatty acids and vitamin E on hormones involved in carbohydrate and lipid metabolism in men.

Forty healthy men were fed diets providing 40% of energy from fat and a minimum of 25 mg vitamin E for 28 wk. During the first 10 wk diets were supplemented with placebo, 15 g mixed fat/d. During the second 10 wk placebo was replaced by 15 g fish-oil concentrate/d. During the last 8 wk 200 mg vitamin E/d was added to fish oil. Compared with placebo, fish-oil feeding significantly increased plasma glucose and decreased triacylglycerol, insulin, glucagon, growth hormone, and somatomedin C. The changes in plasma cholesterol, cortisol, and dehydroepiandrosterone sulphate (DHEA-S) were not significant. Fish oil plus vitamin E further decreased insulin, growth hormone, and DHEA-S and reversed the effect of fish-oil on somatomedin C. The changes in glucose, glucagon, growth hormone, and cortisol were not significant. Thus, changes in plasma glucose and lipids caused by dietary fish oil alone and with fish oil plus vitamin E appear to be due to alterations in hormones involved in carbohydrate and lipid metabolism.

Dietary fish oil-induced changes in the distribution of alpha-tocopherol, retinol, and beta-carotene in plasma, red blood cells, and platelets: modulation by vitamin E.

Healthy men (ages 24-57 y) were fed a controlled basal diet supplemented with 15 g/d of placebo oil (PO) for 10 wk followed by 15 g/d of fish-oil concentrate (FO) (fortified with 15 mg all-rac-tocopherol) for 10 wk without additional alpha-tocopherol and the last 8 wk with 200 mg alpha-tocopherol/d (FO+E). Compared with PO, FO raised plasma malondialdehyde; lowered alpha-tocopherol in plasma, red blood cells, and platelets; and raised plasma and platelet beta-carotene. Supplementation with additional alpha-tocopherol (FO+E) not only restored tocopherol concentrations but also reversed the rise in beta-carotene. The response in retinol, particularly in platelets, showed an inverse relationship to beta-carotene, alpha-tocopherol exhibiting a modulating effect on these changes. From these observations it is postulated that platelets may be a significant extraintestinal site of retinol formation from beta-carotene.

Selective responses of hormones involved in carbohydrate and lipid metabolism and properties of erythrocyte membranes during the menstrual cycle in premenopausal women consuming moderate amounts of alcohol.

The effects of chronic consumption of moderate amounts of alcohol on hormones associated with lipid and carbohydrate metabolism, plasma concentrations of triacylglycerol and cholesterol, insulin receptors on erythrocyte membranes, and erythrocyte membrane fluidity were studied during three phases of the menstrual cycle in 37 premenopausal women. Subjects were given either 30 g ethanol or an equienergetic fruit juice for three menstrual cycles in a crossover design. Blood samples were analyzed during the luteal, midcycle, and follicular phases. Administration of alcohol induced a significant rise in plasma glucagon and cortisol uniformly across the entire menstrual cycle. A similar rise in plasma growth hormone was observed at midcycle during the period when subjects consumed alcohol. A marginal effect was observed on cholesterol and somatomedin C concentrations. Insulin binding to erythrocyte ghosts was not affected by either alcohol or menstrual-cycle phase. Erythrocyte membranes were more fluid during the follicular phase than during the luteal phase of the menstrual cycle when the women were consuming the alcohol. There were no perceptible interactions between alcohol and phases of the menstrual cycle for the indexes studied, except membrane fluidity.

Hormones regulating lipid and carbohydrate metabolism in premenopausal women: modulation by dietary lipids.

The effect of high- and low-fat diets with different levels of fatty acid unsaturation on plasma hormones involved in lipid metabolism was studied during different phases of the menstrual cycle in 31 premenopausal women. Subjects were divided into two groups and were fed controlled diets containing 39% fat with a ratio of polyunsaturated to saturated fatty acids (P:S) of either 0.3 or 1.0 for four menstrual cycles and then switched to a 19% fat diet with the same P:S for another four cycles. Blood samples were analyzed during both the follicular and luteal phases. A significant direct effect of level of dietary fat was observed on plasma cortisol and dehydroepiandrosterone-sulphate whereas an inverse relationship was seen for plasma insulin. Both plasma insulin and growth hormone levels were higher during the luteal compared with the follicular phase of the menstrual cycle. None of the hormones was affected by the level of unsaturation of dietary fats.

Dietary fat and menstrual-cycle effects on the erythrocyte ghost insulin receptor in premenopausal women.

The effect of high- and low-fat diets with different levels of fatty acid unsaturation on insulin receptors of erythrocyte ghosts was studied during different phases of the menstrual cycle in 31 healthy premenopausal women. Subjects were divided into two groups and consumed controlled diets containing 39% fat with a ratio of polyunsaturated to saturated fatty acids (P:S) of either 0.30 or 1.00 for four menstrual cycles. They were switched to 19% fat at the same P:S for another four cycles. Fasting blood samples were collected during the follicular and luteal phases. Insulin receptors were measured from right-side-out ghosts. Insulin binding was significantly lower due to fewer receptors when subjects were fed the low-fat, high-carbohydrate diet compared with the high-fat, low-carbohydrate diet. There was no significant effect of level of unsaturation or time of menstrual cycle on insulin binding. Thus, insulin receptors on erythrocytes respond to dietary lipids.

Effects of fat level, feeding period, and source of fat on lipid fluidity and physical state of rabbit plasma lipoproteins.

Elevating fat content from 5 to 20% of diet by weight or extending the feeding period from 6 months to more than 1 year did not substantially alter the fluidity of rabbit plasma lipoprotein lipid domains. Dietary fatty acid saturation was not adequate as a predictor of lipoprotein fluidity. Rabbits fed corn oil, high in polyunsaturated fatty acid content, did not have more fluid lipoproteins than rabbits fed cocoa butter which contains a high level of saturated long chain fatty acids. Order parameters calculated from fluorescence depolarization measurements with diphenylhexatriene (DPH) showed that very low density lipoprotein (VLDL) lipids were in highly fluid or 'liquid' states at or below body temperature. Order parameter data showed transitions from ordered phase to isotropic liquid in low density lipoproteins (LDL) that were heretofore unnoted with DPH fluorescence depolarization measurements. The transition temperature was inversely related to the LDL triglyceride content, indicating probe intercalation between the fatty acyl chains of the core triacylglycerols in VLDL and LDL.

Influence of dietary fats on the fluidity of the lipid domains of rabbit plasma lipoproteins.

The effects of dietary stearic and other saturated fatty acids on the fluidity of the plasma lipoproteins were assessed with fluorescence polarization techniques. Rabbits were maintained on diets containing either cocoa butter, milkfat, coconut oil, or corn oil as the only source of fat. Microviscosities eta, of the lipid regions of plasma very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL) were determined by measuring the anisotropy of fluorescence from the probe 1,6-diphenyl-1,3,5-hexatriene. The microviscosity values followed the sequence eta HDL greater than eta LDL greater than eta VLDL when the lipoproteins were isolated from the plasma of rabbits fed cocoa butter, milkfat, or corn oil, HDL and LDL consist of an invariant phase in the temperature range 0--50 degrees C regardless of diet. VLDL from rabbits fed milkfat, corn oil, or cocoa butter displayed monophasic behavior in the same range, while VLDL, from rabbits fed coconut oil showed a phase transition at 31.9 +/- 3.7 degrees C. Lipoproteins were less fluid in fasted than in non-fasted rabbits and VLDL and LDL from fasted milkfat-fed rabbits showed phase transitions. Despite the fatty acid compositions of the dietary fats, VLDL and LDL were more fluid from rabbits fed cocoa butter than from rabbits fed corn oil; apparently metabolism influences microviscosity.

Influence of saturated and unsaturated fats on platelet fatty acids in cholesterol-fed rabbits.

Feeding natural fats varying in contents of palmitate (16:0), stearate (18:0), oleate (18:1), and linoleate (18:2) to rabbits resulted in modulation of platelet phospholipid fatty acyl composition. Rabbits were fed high fat semipurified diets containing 2% corn oil (CO) + 18% CO, cocoa butter (CB) or milkfat (M) for periods of up to 300 d. Platelet phospholipid linoleate contents corresponded to diet levels with 18:2 highest in CO-fed rabbits and following the sequence CO greater than CB greater than M. Stearate was highest in CB-fed rabbits, corresponding to high 18:0 levels in CB, but palmitate levels were not affected by diet. Both CB and M-fed rabbits were higher than CO-fed rabbits in oleate. Though CO is highest in 18:2, the accepted 20:4 precursor, arachidonate was highest in M-fed rabbits. Adding cholesterol (0.2%) to the diets did not affect platelet phospholipid fatty acyl composition except to elevate 20:4 in M-fed rabbits. CO-fed rabbits showed uniquely high levels of tetracosadienoate (24:2). Fatty acyl composition data were essentially constant between 200 and 300 d on diet. Phospholipid fatty acyl unsaturation was apparently homeostatically controlled as mole percent unsaturate to saturate ratios were independent of diet. The observed homeostasis resulted in minimal diet influences on platelet membrane fluidity and ADP or collagen stimulated platelet aggregation. Platelet fluidity, determined by fluorescence polarization, was a function of oleate and linoleate contents of the cells. Cholesterol feeding generally lowered platelet fluidity and altered the dependence of fluidity on fatty acyl composition.

Platelet membrane fluidity and aggregation of rabbit platelets.

Aggregation of rabbit platelets from citrated plasma in response to ADP was directly correlated with platelet plasma membrane fluidity as determined by fluorescence depolarization measurements with the probe diphenylhexatriene. Rabbits were maintained for periods of 200 and 400 days on potentially hyperlipidemic diets (20% fat by weight) with varying levels of saturated and polyunsaturated fatty acids. Dietary variations were effective in modulating the mole percentage distribution patterns of the platelet phospholipid fatty acids. The major chemical control of membrane fluidity was the actual mass of unsaturated lipid in the cells and not simply the relative percentage distributions of such unsaturated fatty acids. Substantially higher phospholipid/protein ratios were observed upon analysis of platelets and platelet membranes from rabbits after 200- than after 400-day diet periods. Accordingly lipid structures were significantly more fluid in either whole platelets or membrane isolates at the end of the shorter diet period. The observations pertaining to the extent of aggregation and membrane fluidity are in consonance with the general role of membrane fluidity in controlling biological activity and support the concept that platelet aggregation is a membrane-associated phenomenon.

Dietary linoleate increases fluidity and influences chemical composition of plasma low density lipoprotein in adult men.

Dietary linoleate was effective to increase LDL fluidity in adult men but did not significantly influence VLDL or HDL fluidities. Lipoproteins were isolated ultracentrifugally from plasma of sixteen healthy, free living male volunteers consuming controlled diets formulated from typical U.S.A. foods to have 35 energy % fat with 10 g (diet L) or 30 g (diet H) linoleate per day, 30-50 g saturated fatty acids/day and the balance mainly monounsaturated fatty acids. Calculated cholesterol intakes were 500 mg/day at each calorie level. Changes in LDL fluidity were detected as differences in diphenylhexatriene (DPH) fluorescence polarization upon crossover between the two controlled diets. Thermotropic measurement of DPH fluorescence anisotropy and compositional analyses indicated that LDL and HDL fluidities were dependent upon phospholipid and triacylglycerol concentrations, respectively, and were modulated by the presence of cholesteryl esters. Fatty acid analyses of the major lipid classes of the isolated lipoproteins indicated that changes, upon diet crossover, in DPH fluorescence anisotropy, were a linear function of the incremental change in LDL phospholipid linoleate. The fluorescent probe described an environment corresponding to the fatty acyl moieties of the phospholipids on the LDL periphery, which composition is apparently under dietary control. It is suggested that the diet induced fluidity changes may affect the conformation of the apoprotein moiety on the LDL surface and thus the potential for LDL interaction with cellular LDL receptors.

Influence of age and sex on composition and lipid fluidity in miniature swine plasma lipoproteins.

Age- and sex-related differences were observed in the plasma cholesterol level, the plasma concentrations of certain lipoprotein components, and the HDL lipid phase fluidity in miniature swine from post-weaning (6 weeks) through puberty (6 months), maturity (2-6 years), and old age (10-12 years). Age effects were more dominant in the males, with VLDL protein; LDL protein, triacylglycerol, and phospholipid; and HDL triacylglycerol, phospholipid, cholesterol, and polyunsaturated fatty acids showing statistically significant negative correlations with age. These effects were not observed in females. HDL cholesterol was positively correlated with age in females. Total plasma cholesterol decreased with age in males only, but plasma triacylglycerol was not influenced by age in either sex. Higher concentrations of all lipoprotein lipids were observed in the female minipigs regardless of age. HDL lipids became less fluid with age in the males alone suggesting a physical chemical basis for the lower incidence of heart disease among females. The more fluid HDL circulating in the female may be more capable of mobilizing peripheral tissue cholesterol for catabolism thus protecting her from developing atherosclerotic lesions.

Dietary fat and hormonal influences on lipoprotein fluidity and composition in premenopausal women.

LDL and HDL became more fluid when health, free-living, premenopausal women were fed reduced fat diets with higher proportions of polyunsaturated fatty acids. Lipoproteins were isolated from plasma of 31 female subjects fed one of two sets of diets from typical U.S.A. foods with P/S ratios of 0.3 or 1.0. All subjects were fed high-fat diets (40% of energy) for the duration of four menstrual cycles followed by low-fat diets (20% of energy) for the next four cycles. Blood samples were collected during mid-follicular and mid-luteal phases of the fourth menstrual cycle of each diet period to assess interactive dietary and hormonal control of lipoprotein fluidity. LDL was significantly more fluid, as determined by DPH fluorescence, upon reducing fat consumption from 40 to 20% of energy for subjects eating foods with P/S = 1.0 or 0.3. Generally LDL was more fluid during the follicular phase than the luteal phase of the cycles, thus indicating hormonal influences on LDL fluidity. HDL results were similar but not as pronounced as with LDL. Lipoprotein phospholipid (PL) and cholesteryl ester (CE) fatty acyl compositions were also subject to dietary and hormonal influences. Effects were noted in several fatty acids depending upon diet and hormonal state; however, generally diet fat reduction resulted in reduced linoleate and increased oleate contents. Regression analyses showed that fluidity was more dependent upon the lipoprotein cholesterol content than upon fatty acyl composition.

Vitamin E levels and susceptibility to lipid peroxidation increase with aging in heart plasma membrane from miniature swine.

Age-related changes in heart plasma membrane fatty acid composition, vitamin E content, membrane fluidity, susceptibility to lipid peroxidation, and the subcellular distribution of vitamin E were observed in male and female Hormel-Hanford miniswine over a wide range of ages: prepubertal, < 0.5 years; young, 0.5-2.5 years; middle-aged, 5.9-10 years; and old, 11.5-13.9 years. Pigs were continuously fed the same low-fat, cholesterol-free, vitamin E-adequate stock diet at restricted maintenance levels. Membrane lipid peroxidation tended to increase in middle-aged and elderly pigs, but not significantly, perhaps being somewhat ameliorated by the significantly increased membrane vitamin E in middle-aged and old pigs. Mid-bilayer membrane fluidity was significantly increased in old pigs, but fluidity of the polar headgroup domains decreased with age. Thus, lipid peroxidation tended to increase over the long life span of miniswine even when they are food restricted.

In vitro regulation of low-density lipoprotein receptor interaction by fatty acids.

Low-density lipoprotein (LDL) receptor binding is the initial step in receptor-mediated clearance. Dietary fat composition is known to affect LDL clearance, but the mechanism of the effect is unknown. We have examined the effects of altered membrane fatty acid composition, as might occur when specific dietary fats are consumed, on LDL binding using a Chinese hamster ovary (CHO) line that constitutively expresses the human LDL receptor. Binding of pooled human LDL to its receptor was compared in cells enriched with various fatty acids. Binding affinity was greater (lower Kd) for cells grown in 16:0-, 18:0-, or 18:1-enriched media than for those grown in 18:2 (P < .0001). The apparent receptor number (Bmax) was lower for cells enriched in saturated fatty acids and 18:1. Fluidity was assessed by measuring diphenylhexatriene (DPH) fluorescence anisotropy (rs). Cells enriched in 18:1 or 18:2 were the most fluid (P < .003). The correlation between binding and fluidity (r = .24, P = .27) was weak and did not appear to explain the effects of fatty acid modification on LDL receptor binding. Thus, it appears that cellular enrichment in 16:0, 18:0, and 18:1 increases binding affinity by affecting properties other than membrane fluidity. Changes in Bmax may also contribute to the observed differences in LDL binding.

Dietary fat and hormonal effects on erythrocyte membrane fluidity and lipid composition in adult women.

Erythrocyte ghost membrane fluidity and phospholipid linoleate were significantly increased when higher levels of polyunsaturated fats were fed to healthy, free living, premenopausal women. Fluidity was assessed by diphenylhexatriene (DPH) fluorescence polarization measurements with hypotonically lysed red blood cells from 31 female subjects fed one of two sets of diets, which were formulated from typical US foods to contain polyunsaturate to saturate ratios (P/S) of 1.0 or 0.3. Both groups of women were fed diets with 40% of energy as fat for four menstrual cycles followed by low-fat diets having 20% of energy as fat for the next four menstrual cycles. Blood was sampled during the fourth cycle of each dietary period at times estimated to correspond to maximum secretions of estrogen and progesterone to assess interactive hormonal and dietary effects on membrane composition and fluidity. Red blood cell membranes were most fluid following higher levels of linoleate intake, either by higher (40%) total fat or higher P/S levels. Membrane fluidity was directly related to the phospholipid oleate and linoleate contents and inversely related to the molar cholesterol/phospholipid ratio. Hormonal status effects on the membranes were not extensive. Membrane fluidity in cells from women fed P/S = 0.3 diets was higher at 40% than at 20% fat during the luteal phase of the fourth cycle. In contrast, women fed the P/S = 1.0 diets had more fluid red cells at 40% fat during the follicular phase of the cycle. Regression analysis showed a direct linear correlation between membrane fluidity and red cell membrane insulin binding demonstrating a relation between receptor binding and cell membrane fluidity in the human female.