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PubMed1978

Plasma radioiron kinetics in man: explanation for the effect of plasma iron concentration.

The plasma iron turnover was measured in 19 normal subjects. A correlation was found between plasma iron concentration and plasma iron turnover. In addition to the turnover of 55Fe at normal plasma iron concentration (predominantly monoferric transferrin), a second turnover in which the labeled plasma was saturated with iron (to produce predominantly diferric transferrin) was studied with 50Fe. It was demonstrated that diferric transferrin had a greater rate of iron turnover but that the distribution between erythroid and non-erythroid tissues was unchanged. It was concluded that plasma iron turnover is dependent on the monoferric/diferric transferrin ratio in the plasma but that the internal distribution of iron is unaffected.

Adult↗
PubMed1979

Interactions among Hageman factor, plasma prekallikrein, high molecular weight kininogen, and plasma thromboplastin antecedent.

To investigate the earliest steps of the intrinsic clotting pathway, Hageman factor (Factor XII) was exposed to Sephadex gels to which ellagic acid had been adsorbed; Hageman factor was then separated from the gels and studied in the fluid phase. Sephadex-ellagic acid-exposed Hageman factor, whether purified or in plasma, activated plasma thromboplastin antecedent, but only when high molecular weight kininogen was presnet. In the absence of plasma prekallikrein, maximal activation of plasma thromboplastin antecedent was slightly delayed in plasma, a delay not observed with similarly treated purified Hageman factor. Thus, high molecular weight kininogen was needed for expression of Hageman factor's clot-promoting properties and plasma prekallikrein played a minor role in the interaction of ellagic acid-treated Hageman factor and plasma thromboplastin antecedent.

Blood Coagulation↗
PubMed1983

Plasma clearance of sulfobromophthalein and its interaction with hepatic binding proteins in normal and analbuminemic rats: is plasma albumin essential for vectorial transport of organic anions in the liver?

To investigate a possible function of plasma albumin in the vectorial transport of organic anions by the liver, the plasma disappearance of sulfobromophthalein (BSP) and its interaction with plasma and liver cytosolic proteins were studied in normal rats and mutant Nagase analbuminemic rats (NAR). After intravenous administration of BSP, plasma BSP decreased rapidly in both NAR and control animals: plasma clearance values of BSP in NAR and controls were 12.45 and 7.40 ml/min per kg, respectively. Gel exclusion Sephadex G-100 chromatography of BSP with control rat serum revealed a protein peak in the void volume and another in the albumin fraction. BSP chromatographed exclusively with the albumin fraction; binding of BSP to plasma albumin occurred stoichiometrically. Similar studies with NAR serum revealed a single protein peak, in the void volume; a small amount of BSP chromatographed with this protein peak. The amount of BSP that chromatographed with NAR serum protein(s) was 8% of that with control rat serum albumin. Sephadex G-100 chromatography of BSP with control rat liver cytosol revealed four peaks of protein-bound BSP in fractions corresponding to the void volume (fraction X), albumin, glutathione S-transferases (fraction Y, Mr 45,000), and fraction Z (Mr 12,000); fraction Y was the major component of BSP binding. Gel chromatography of NAR liver cytosol with BSP revealed three BSP peaks, fractions X, Y, and Z; fraction X was the major component of BSP binding. Total BSP binding by 30 mg of hepatic cytosolic proteins was 4.5 nmol for controls and 10.4 nmol for NAR. Isoelectric focusing of liver cytosol revealed no quantitative or qualitative differences in glutathione S-transferase isozymes between control and mutant animals. Intravenously administered BSP (5 mumol/kg) rapidly appeared in bile as the free form and the glutathione conjugate in normal rats and NAR; 41% and 57% of injected BSP was excreted within 60 min in NAR and control rat bile, respectively. These results indicate that binding of BSP to plasma albumin is not indispensable to transhepatocyte transport of BSP in vivo.

Animals↗
PubMed1980

Neutrophil plasma membranes. I. High-yield purification of human neutrophil plasma membrane vesicles by nitrogen cavitation and differential centrifugation.

Neutrophil chemotaxis, phagocytosis, and oxygen-dependent microbicidal activity are initiated by interactions of stimuli with the plasma membrane. However, difficulties in neutrophil plasma membrane isolation have precluded studies on the precise structure or function of this cellular component. In this paper, a method is described for the isolation of representative human neutrophil plasma membrane vesicles, using nitrogen cavitation for cell disruption and a combination of differential centrifugation and equilibrium ultracentrifugation in Dextran gradients for membrane fractionation. Multiple biochemical markers and galactose oxidase-tritiated sodium borohydride surface labeling were employed to follow the yield, purity, and distribution of plasma membranes, nuclei, lysosomes, endoplasmic reticulum, mitochondria, and cytosol. According to these markers, neutrophil plasma membranes were exposed to minimal lysosomal hydrolytic enzymes and could be isolated free of other subcellular organelles. In contrast, disruption of neutrophils by mechanical homogenization resulted in > 20% lysosomal rupture and significant plasma membrane proteolysis. Electron microscopy demonstrated that plasma membranes isolated after nitrogen cavitation appeared to be sealed vesicles with striking homogeneity.

Cell Fractionation↗
PubMed1994

High plasma vitamin C associated with high plasma HDL- and HDL2 cholesterol.

High plasma vitamin C may lower risk of cardiovascular disease as indicated by direct association with plasma high-density-lipoprotein (HDL) cholesterol and HDL2 cholesterol. Plasma lipids and vitamin C were determined in 316 women and 511 men (aged 19-95 y). After adjustment for age, sex, obesity, and smoking, plasma vitamin C was directly associated with HDL- (P = 0.01) and HDL2 cholesterol (P = 0.0002). When men and women with diseases that might affect lipids were excluded, associations between plasma vitamin C and HDL- and HDL2 cholesterol persisted, though the relationships were strongest in older men. Comparisons of diets in a subset (n = 485) who completed 7-d diet records were made. Total fat, saturated fatty acids, energy from fat, and cholesterol intakes were not associated with plasma vitamin C. Mean intakes of vitamin C were well above recommended dietary allowances. These findings suggest that high plasma concentrations of vitamin C may lower atherogenic risk.

Adult↗
PubMed1997

Plasma retinol and plasma and lipoprotein tocopherol and carotenoid concentrations in healthy elderly participants of the Framingham Heart Study.

Data on plasma concentrations of tocopherols and the major carotenoids in adults aged > or = 65 y, particularly in those > 80 y, are sparse. In the current study retinol, tocopherol (alpha- and gamma-tocopherols), and carotenoid (lutein/zeaxanthin, cryptoxanthins, lycopene, and alpha- and beta-carotene) concentrations were determined in 638 subjects, 230 men (aged 75 +/- 5 y) and 408 women (76 +/- 6 y), of the Framingham Heart Study. All subjects were free of clinical evidence of cardiovascular disease and cancer. Percentile ranges were comparable with those established in younger cohorts. Moreover, women had significantly higher plasma alpha-tocopherol and plasma and lipoprotein concentrations of beta-cryptoxanthin and alpha- and beta-carotene than did men. Lycopene concentrations were inversely correlated with age and lowest among subjects > or = 80 y. Total intakes (diet+supplements) of vitamin C and vitamin E, but not dietary intakes alone, were positively associated with plasma alpha-tocopherol and inversely associated with gamma-tocopherol concentrations. In multivariate analyses, plasma cholesterol and triacylglycerol concentrations and total intake of vitamins E and C predicted 64% and 55% of the plasma alpha-tocopherol concentrations in men and women, respectively. Important predictors for the majority of carotenoids included plasma cholesterol concentration, body mass index (negative effect), and smoking status (negative effect); for lycopene concentration they included cholesterol concentration and age (negative effect). In summary, percentile ranges and lipoprotein distributions were comparable with those established in younger cohorts, suggesting that overall antioxidant status is not altered in people between the ages of 67 and 96 y.

Aged↗
PubMed1992

L-carnitine administration and withdrawal affect plasma and hepatic carnitine concentrations, plasma lipid and lipoprotein composition, and in vitro hepatic lipogenesis from labeled mevalonate and oleate in normal rabbits.

Carnitine was administered to normal rabbits to investigate the possible effects of pharmacologic doses on various aspects of normal lipid and lipoprotein metabolism. Carnitine concentrations were measured in the plasma and liver of normal rabbits that received L-carnitine orally [40 mg/(kg.d)] for 21 d and after withdrawal from the carnitine supplement for 21 d. Plasma lipids, plasma lipoprotein composition and in vitro hepatic lipid biosynthesis from [2-14C]mevalonate and [1-14C]oleate were also measured. Threefold elevations in plasma carnitine with carnitine treatment were essentially reversed after 48 h of carnitine withdrawal, but elevated hepatic carnitine accumulation (twofold) persisted for 21 d, suggesting that the accumulated carnitine constituted a pool that is only slowly miscible with plasma. The rabbits withdrawn from L-carnitine for 21 d experienced a 35% decrease in plasma cholesterol, a 50% decrease in VLDL cholesterol, and an increase in the protein content of HDL and of intermediate density lipoprotein + LDL. Additionally, the proportion of [14C]oleate incorporated into hepatic phospholipids increased 35% at the expense of triglyceride and the ratio of hepatic [14C]cholesterol to [14C]squalene derived from [14C]mevalonate increased over twofold following carnitine withdrawal. These studies provide evidence that normal lipid homeostasis can be altered by supplemental carnitine and that the perturbations are reflected by changes in plasma lipids and lipoproteins and in the proportions of the hepatic lipids synthesized.

Administration, Oral↗
PubMed1996

Plasma fibrinogen and its relationship to plasma sialic acid in non-insulin-dependent diabetes mellitus.

Serum or plasma sialic acid (SA) has been shown to be a possible risk factor for cardiovascular disease and to be elevated in diabetes mellitus. We postulated that plasma SA may be related to plasma fibrinogen, another reputed cardiovascular risk factor. We decided to test this hypothesis in 27 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 27 age- and sex-matched control subjects. Plasma fibrinogen was significantly elevated in the diabetic patients compared with the control subjects (3.4 +/- 1.5 g/l versus 2.2 +/- 0.6 g/l, P < 0.001). Similarly, plasma SA was elevated in the diabetic patients in comparison with the control subjects (0.74 +/- 0.14 g/l versus 0.62 +/- 0.08 g/l, P < 0.001). There was a strong univariate correlation between plasma fibrinogen and plasma SA in both NIDDM patients (r = 0.80, P < 0.001) and control subjects (r = 0.54, P < 0.01).

Aged↗
PubMed1994

Increased plasma concentrations of soluble tumor necrosis factor receptors in sepsis syndrome: correlation with plasma creatinine values.

OBJECTIVES: Tumor necrosis factor (TNF) is an important mediator in the complex pathophysiology of sepsis syndrome. Although a positive correlation with mortality rate has been demonstrated, TNF has not been found consistently in sepsis. Since prolonged increases in soluble TNF receptor concentrations were demonstrated after endotoxin and TNF administration, we investigated whether the measurement of TNF receptor concentrations could provide a better indicator of disease than plasma TNF and interleukin (IL)-6 concentrations. DESIGN: Prospective analysis. SETTING: General intensive care unit (ICU) of a university hospital. PATIENTS: Twenty-six patients with sepsis syndrome and proven bacteremia. MEASUREMENTS AND MAIN RESULTS: Plasma peak concentrations of the soluble 55-kilodalton molecular weight TNF receptor were significantly higher (p < .005) in nonsurvivors compared with survivors of sepsis syndrome, whereas the difference in peak concentrations of the soluble 75-kilodalton TNF receptor did not reach significance (p = .06). In contrast to TNF peak concentrations (p = .14), significantly higher (p < .05) IL-6 peak concentrations were measured in nonsurvivors. Besides the positive correlation between the soluble 55-kilodalton TNF receptor and the soluble 75-kilodalton TNF receptor (r2 = .68; p < .0001), peak concentrations of both soluble 55-kilodalton TNF receptor and 75-kilodalton TNF receptor correlated significantly with plasma creatinine values, an indicator of renal function (r2 = .60; p < .0001 and r2 = .44; p < .001, respectively). Plasma creatinine concentrations were significantly higher in nonsurvivors (p < .001). CONCLUSIONS: In the population studied, plasma-soluble TNF receptor concentrations correlated with outcome as well as with plasma creatinine concentrations. The data presented suggest that increased plasma-soluble TNF receptor concentrations in patients with sepsis syndrome are merely the result of renal failure complicating sepsis, and are similarly correlated with mortality rate.

Adult↗
PubMed1988

A comparative spin-label study of isolated plasma membranes and plasma membranes of whole cells and protoplasts from cold-hardened and nonhardened winter rye.

Lipid-lipid and lipid-protein interactions in the plasma membranes of whole cells and protoplasts and an isolated plasma membrane fraction from winter rye (Secale cereale L. cv Puma) have been studied by spin labeling. Spectra were recorded between -40 degrees C and 40 degrees C using the freely diffusing spin-label, 16-doxyl stearic acid, as a midbilayer membrane probe. The probe was reduced by the whole cells and protoplasts and reoxidized by external potassium ferricyanide. The reoxidized probe was assumed to be localized in the plasma membrane. The spectra consisted of the superposition of a narrow and a broad component indicating that both fluid and immobilized lipids were present in the plasma membrane. The two components were separated by digital subtraction of the immobilized component. Temperature profiles of the membranes were developed using the percentage of immobilized lipid present at each temperature and the separation between the outermost hyperfine lines for the fluid lipid component. Lipid immobilization was attributed to lipid-protein interactions, lipid-cell wall interactions, and temperature-induced lipid phase transitions to the gel-state. Temperature profiles were compared for both cold-hardened and nonhardened protoplasts, plasma membranes, and plasma membrane lipids, respectively. Although cold-hardening extended the range of lipid fluidity by 5 degrees C, it had no effect on lipid-protein interactions or activation energies of lipid mobility. Differences were found, however, between the temperature profiles for the different samples, suggesting that alterations in the plasma membrane occurred as a consequence of the isolation methods used.

Journal Article↗
PubMed1988

Plasma lipids and plasma lipoproteins in diabetics with and without proliferative retinopathy.

The single most important factor related to the development of diabetic retinopathy is the duration of diabetes. Little is known about the underlying mechanisms, but many factors have been suggested to be involved, among them derangements in plasma lipids and plasma lipoproteins. In the present study we examined the relation between plasma lipids, plasma lipoproteins, and the duration of diabetes in Type I diabetics with and without proliferative retinopathy. The duration of diabetes in the two groups was 12.2 +/- 2.8 and 21.5 +/- 9.0 years, respectively (mean +/- SD; p less than 0.01). Except for moderately low HDL levels, plasma lipid and lipoprotein concentrations were normal in both groups of patients. The levels of lipids and lipoproteins did not correlate with the duration of diabetes. Furthermore, no differences were seen between patients with and without proliferative retinopathy. Thus, the present study does not indicate that plasma lipids and plasma lipoproteins play any major role in the development of diabetic proliferative retinopathy.

Adult↗
PubMed1981

Studies of diurnal changes in plasma renin activity, and plasma noradrenaline, aldosterone and cortisol concentrations in man.

Diurnal studies were performed on ten normal volunteers taking a normal sodium diet. Half-hourly blood samples were taken throughout 25 h and assayed for plasma renin activity (PRA) and the plasma concentrations of noradrenaline, aldosterone and cortisol. Sleep was recorded polygraphically and scored by standard criteria. Circadian rhythms were demonstrated for plasma cortisol, aldosterone and noradrenaline concentrations, but not for plasma renin activity. The nadir of the rhythm for the noradrenaline concentration appeared to be related to sleep itself rather than to any chronological index. Only PRA was effected by the stage of sleep, falling sharply during periods of REM sleep. Plasma cortisol and aldosterone concentrations showed a positive correlation over the 24 h. There was, however, no correlation between PRA and plasma aldosterone concentrations, except when the subjects arose after their night's recumbency. Plasma noradrenaline concentration did not correlate with the concentration of any of the other hormones measured.

Adult↗
PubMed1990

Effect of non-linear plasma protein binding on unbound and total plasma phenylbutazone concentrations in cows.

The influence of plasma protein binding on unbound and total phenylbutazone concentrations in cows was examined employing data from the literature. Protein binding parameters (number of binding sites and affinity constants) were generated by computer analysis to characterize the concentration-dependent plasma protein binding of phenylbutazone. Unbound plasma phenylbutazone concentrations were calculated from total plasma drug concentrations observed after administration of a single dose of phenylbutazone to cows. Pharmacokinetic parameters for unbound phenylbutazone were obtained. Parameters characterizing the plasma protein binding and pharmacokinetics of unbound phenylbutazone derived from single-dose administration were then used to predict unbound and total drug concentrations after multiple-dose administration of phenylbutazone. Total plasma phenylbutazone concentrations predicted from single-dose pharmacokinetic parameters agreed well with observed values following multiple-dose administration of the drug. Thus, the results of this analysis demonstrate that the non-linear pharmacokinetics of phenylbutazone in the cow can be attributed to the concentration-dependent plasma protein binding of the drug.

Animals↗
PubMed1991

Acute effects of exercise on plasma lipids, noradrenaline levels and plasma volume.

1. Total plasma cholesterol, high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), noradrenaline, haematocrit, haemoglobin and heart rate were measured in blood sampled from an antecubital vein in nine volunteers after 1 min standing and at intervals up to 1 h following 5 min of vigorous bicycle exercise. 2. Heart rates and plasma noradrenaline levels rose substantially immediately following exercise and gradually returned toward baseline levels 60 min post-exercise. 3. Total plasma cholesterol levels rose by 24% immediately post-exercise and slowly returned to baseline levels 60 min post-exercise. Similar changes were observed for LDL-C (20.2%) and HDL-C (27.7%). As a result, LDL:HDL ratios did not alter. 4. These changes in total plasma cholesterol, HDL-C and LDL-C were explained by changes in plasma volume that occurred as a consequence of vigorous exercise. 5. Changes in plasma volume may be a mechanism by which some environmental factors such as stress are associated with elevated plasma cholesterol levels.

Adult↗
PubMed1984

A comparison of saliva, plasma unconjugated and plasma total oestriol levels throughout normal pregnancy.

Saliva unconjugated, plasma unconjugated and plasma total oestriol (E3) levels were measured longitudinally, by radioimmunoassay, in 25 normal women from 13 weeks gestation until delivery. The increase in salivary unconjugated oestriol closely paralleled that of plasma unconjugated oestriol and to a lesser extent that of plasma total oestriol. In each patient the percentage value of salivary E3/plasma unconjugated E3 x 100 was virtually constant throughout pregnancy but this percentage varied from one patient to another (mean 14.4%). The overall correlation coefficient (r) for salivary and plasma unconjugated E3 was 0.90. The variability in salivary levels in samples collected at daily, hourly, 15 min and 5 min intervals (12.7, 13.4, 10.1 and 9.3%) was similar to that previously described for plasma unconjugated E3. There was no distinct pattern in diurnal variation. It seems probable that measurement of salivary E3 could adequately replace that of plasma unconjugated E3 in the assessment of fetoplacental function.

Circadian Rhythm↗
PubMed1995

Growth, fatty acid composition of plasma lipid classes, and plasma retinol and alpha-tocopherol concentrations in full-term infants fed formula enriched with omega-6 and omega-3 long-chain polyunsaturated fatty acids.

Full-term infants fed formula without dietary long-chain polyunsaturated fatty acids (LCF) exhibit significantly lower plasma LCP values than breast-fed infants. We studied prospectively two groups of healthy full-term infants fed conventional infant formula without LCP (F, n = 10) or the same formula enriched with both omega-6 and omega-3 LCP (LCP-F, n = 12). Anthropometric data were obtained and fatty acid (FA) compositions of plasma phospholipids, triglycerides and sterol esters as well as plasma retinol and alpha-tocopherol concentrations were determined at 5 days and 1, 2, 3 and 4 months of age. Gains in weight, length and head circumference did not differ between the two groups throughout the study period. Plasma FA values did not differ at 5 days of age. Between 1 and 4 months of age, plasma phospholipids of infants fed LCP-F consistently had significantly (p < 0.05) higher percentages of arachidonic acid (1 month: 9.7 (0.8) versus 7.0 (1.3) %wt/wt, 4 months: 8.7 (0.5) versus 6.6 (1.0) %wt/wt, median (interquartile range), LCP-F versus F) and docosahexaenoic acid (1 month: 2.9 (0.5) versus 1.6 (0.3) %wt/wt; 4 months: 2.9 (0.4) versus 0.9 (0.3) %wt/wt). Plasma retinol and alpha-tocopherol concentrations did not differ between the two groups throughout the study. We conclude that this form of LCP enrichment of formula for full-term infants effectively enhances plasma LCP contents without detectable adverse effects. The potential effects on functional outcome need to be studied carefully in prospective clinical trials.

Age Factors↗
PubMed1994

Immunoreactive insulin-like growth factor I and insulin in blood plasma and milk of mares and in blood plasma of foals.

Concentration of (total) globulin was relatively stable in blood plasma of mares, but rapidly decreased in colostrum to very low levels within 2 days after parturition. In foals, after intake of the first colostrum, globulin increased within 1 day in blood plasma, but remained at lower concentrations than those measured in mare plasma. Concentrations of immunoreactive insulin (iI) were high during the first 2 months of lactation in blood plasma of mares and then decreased, were high in first colostrum and then decreased drastically, and remained at low concentrations up to weaning in blood of foals. In mares, concentration of immunoreactive insulin-like growth factor I (iIGF-I) in plasma increased during late pregnancy, peaked 2 days after parturition, and then gradually declined until weaning. iIGF-I was highest in first colostrum and then dramatically decreased within the first 2 days of lactation. In foals, iIGF-I gradually increased over the first 2 months of life. IGF-I in the horse appears to be bound to proteins of similar molecular weight as in cattle. The study demonstrates different patterns of changes in plasma iIGF-I and iI concentrations in mares and their foals, whereas iI, iIGF-I and globulin changes in colostrum and milk occurred in parallel. Furthermore, plasma iI and iIGF-I behaved differently, while colostrum iI and iIGF-I behaved similarly, in mares compared with dairy cows.

Animals↗
PubMed1977

Plasma creatinine and urea: creatinine ratio in patients with raised plasma urea.

We examined the plasma urea and creatinine concentrations and the ratio between them according to diagnosis in 100 unselected and 31 selected adult hospital patients with a plasma urea concentration greater than or equal to 10 mmol/l (60mg/100ml). We also examined plasma urea and creatinine concentrations in 350 unselected consecutive patients, but found no useful relation between the two values. Congestive heart failure was the most common identifiable cause of a raised plasma urea concentration in the 100 unselected patients (36%). Among these 100 patinets the plasma creatinine concentration was a more useful discriminant between prerenal uraemia and intrinsic renal failure than was the urea:creatinine ratio or the plasma urea concentration. A plasma creatinine concentration greater than 250 mumol/1 (2-8 mg/100ml) indicated intrinsic renal failure with a 90% probability.

Acute Kidney Injury↗