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Threshold increases in plasma growth hormone in relation to plasma catecholamine and blood lactate concentrations during progressive exercise in endurance-trained athletes.

Plasma human growth hormone ([HGH]), adrenaline ([A]), noradrenaline ([NA]) and blood lactate ([La-](b)) concentrations were measured during progressive, multistage exercise on a cycle ergometer in 12 endurance-trained athletes [aged 32.0 (SEM 2.0) years]. Exercise intensities (3 min each) were increased by 50 W until the subjects felt exhausted. Venous blood samples were taken after each intensity. The [HGH] and catecholamine concentrations increased negligibly during exercise of low to moderate intensities revealing an abrupt rise at the load corresponding to the lactate threshold ([La-]-T). Close correlations (P <0.001) were found between [La-]b and plasma [HGH] (r = 0.64), [A] (r = 0.71) and [NA] (r = 0.81). The mean threshold exercise intensities for [HGH], [A] and [NA], detected by log-log transformation, [154 (SEM 19) W, 162 (SEM 15) W and 160 (SEM 17) W, respectively] were not significantly different from the [La-]-T [161 (SEM 12) W]. The results indicated that the threshold rise in plasma [HGH] followed the patterns of plasma catecholamine and blood lactate accumulation during progressive exercise in the endurance-trained athletes.

Adult↗

Fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and urinary C-peptide in relation to clinical type of diabetes.

Many patients with Type 2 (non-insulin-dependent) diabetes mellitus are treated with insulin in order to control hyperglycaemia. We studied fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and 24 h urinary C-peptide in relation to clinical type of diabetes in 132 insulin treated diabetic subjects. Patients were classified clinically as Type 1 (insulin-dependent) diabetic subjects in the presence of at least two of the following criteria: 1) significant ketonuria, 2) insulin treatment started within one year after diagnosis, 3) age of diagnosis less than or equal to 40 years, and 4) weight below 110% of ideal weight of the same age and sex. Eighty patients were classified as Type 1 and 52 as Type 2 diabetic subjects. A second classification of patients into 6 C-peptide classes was then performed. Class I consisted of patients without islet B-cell function. Class II-VI had preserved islet B-cell function and were separated according to the 20%, 40%, 60% and 80% C-peptide percentiles. The two classifications of patients were compared by calculating the prevalence of clinical Type 1 and Type 2 diabetes in each of the C-peptide classes. This analysis showed that patients with a fasting plasma C-peptide value less than 0.20 nmol/l, a glucagon stimulated plasma C-peptide value less than 0.32 nmol/l, and a urinary C-peptide value less than 3.1 nmol/l, or less than 0.54 nmol/mmol creatinine/24 h, or less than 5.4 nmol/24 h mainly were Type 1 diabetic patients; while patients with C-peptide levels above these values mainly were Type 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A comparison between the composition of maternal peripheral plasma and plasma collected from the retroplacental compartment at caesarean section. A study on protein and steroid hormones and binding proteins.

In the pregnant uterus unique immunological conditions must prevail. Since compounds of possible fetoplacental origin may modulate the local maternal immunological response, higher concentrations of such compounds in the vicinity of the conceptus might be expected. We have measured the concentrations of several compounds in peripheral and retroplacental plasma, mainly by immunological methods, from women delivered by caesarean section in pregnancy week 38-40. Significantly higher (P less than 0.001) retroplacental concentrations were found for human placental lactogen, prolactin, alpha-fetoprotein, tissue polypeptide antigen, non-conjugated estriol and progesterone. Peripheral plasma levels were significantly higher for cortisol (P less than 0.01), transcortin (P less than 0.001) and sex-hormone binding globulin (P less than 0.002). No difference was found for albumin, alpha 2-macroglobulin, estradiol, placental alkaline phosphatase and human chorionic gonadotrophin. Significant correlations between retroplacental and maternal peripheral plasma levels were found for progesterone, cortisol, estradiol, estriol, transcortin, sex-hormone binding globulin, prolactin, human placental lactogen, human chorionic gonadotrophin, placental alkaline phosphatase, albumin and alpha 2-macroglobulin. There were also significant correlations between estradiol and sex-hormone binding globulin as well as transcortin in peripheral maternal plasma.

Adult↗

Histamine as a ligand in blood plasma. Part 5. Computer simulated distribution of metal histamine complexes in normal blood plasma and discussion of the implications of a possible role of zinc and copper in histamine catabolism.

Previously physiological experiments carried out on mice have proved that copper and zinc can interfere with the pharmacological effects of histamine that lead to anaphylactic shock. A quantitative study of the interactions between essential metal ions and histamine in plasma was thus undertaken. The progressive approach towards a reliable computer-simulated distribution of the histamine-containing plasma species necessitated a large series of physicochemical determinations of the formation constants of the binary and ternary metal complexes involved. The present paper deals with the determination of the formation constants in the zinc-serine, zinc-histamine-serine, zinc-histamine-lysine, copper-serine, copper-histamine-serine, and copper-histamine-valine systems, which were still necessary to reach the reliable simulation required. The subsequent final distribution of histamine in plasma has thus been computed, and interpreted in terms of a possible role for zinc in assisting the histamine catabolism process. Further computer calculations simulating the increase of the zinc concentration in human blood plasma support this interpretation. The antagonizing role of copper against that of zinc has also been examined.

Animals↗

The effects of jaundiced plasma and hypercholesterolaemic plasma on vascular sensitivity to injected noradrenaline.

Jaundiced plasma and plasma from hyperlipidaemic patients was perfused into an isolated artery or kidney preparation. The responses of the artery to doses of noradrenaline when Krebs solution was perfused were compared to the responses when the plasmas were perfused. It was found that both jaundiced and hyperlipidaemic plasmas potentiated the effects of noradrenaline on the isolated arteries and kidneys.

Animals↗

The effect of dietary fat level and quality on plasma lipoprotein lipids and plasma fatty acids in normocholesterolemic subjects.

This study examined the effect on the plasma lipids and plasma phospholipid and cholesteryl ester fatty acids of changing froma typical western diet to a very low fat (VLF) vegetarian diet containing one egg/day. The effect of the addition of saturated, monounsaturated or polyunsaturated fat (PUFA) to the VLF diet was also examined. Three groups of 10 subjects (6 women, 4 men) were fed the VLF diet (10% energy as fat) for two weeks, and then in the next two weeks the dietary fat in each group was increased by 10% energy/week using butter, olive oil or safflower oil. The fat replaced dietary carbohydrate. The VLF diet reduced both the low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol levels; addition of the monounsaturated fats and PUFA increased the HDL-cholesterol levels, whereas butter increased the cholesterol levels in both the LDL- and HDL-fractions. The VLF diet led to significant reductions in the proportion of linoleic acid (18:2 omega 6) and eicosapentaenoic acid (20:5 omega 3) and to increases in palmitoleic (16:1), eicosatrienoic (20:3 omega 6) and arachidonic acids (20:4 omega 6) in both phospholipids and cholesteryl esters. Addition of butter reversed the changes seen on the VLF diet, with the exception of 16:1, which remained elevated. Addition of olive oil resulted in a significant rise in the proportion of 18:1 and significant decreases in all omega 3 PUFA except 22:6 compared with the usual diet. The addition of safflower oil resulted in significant increases in 18:2 and 20:4 omega 6 and significant decreases in 18:1, 20:5 omega 3 and 22:5 omega 3. These results indicate that the reduction of saturated fat content of the diet (< 6% dietary energy), either by reducing the total fat content of the diet or by exchanging saturated fat with unsaturated fat, reduced the total plasma cholesterol levels by approximately 12% in normocholesterolemic subjects. Although the VLF vegetarian diet reduced both LDL- and HDL-cholesterol levels, the long-term effects of VLF diets are unlikely to be deleterious since populations which habitually consume these diets have low rates of coronary heart disease. The addition of safflower oil or olive oil to a VLF diet produced favorable changes in the lipoprotein lipid profile compared with the addition of butter. The VLF diets and diets rich in butter, olive oil or safflower oil had different effects on the 20 carbon eicosanoid precursor fatty acids in the plasma.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

The effect of the area under the plasma concentration vs time curve and the maximum plasma concentration of esomeprazole on intragastric pH.

OBJECTIVE: The aim of this study was to create a useful model of the effect of the area under the plasma concentration vs time curve (AUC) and the maximum plasma concentration (C(max)) of esomeprazole on intragastric pH, measured as the percentage of total time with intragastric pH above 4 (%pH>4) during a 24-h period. METHODS: The evaluation is based on esomeprazole data from two crossover studies. In the first study ( n=36), intragastric pH and plasma concentrations were measured on day 5 of repeated once-daily 20-mg and 40-mg doses of esomeprazole during fasting conditions. In the second study ( n=24), measurements were made on days 1 and 5 of repeated once-daily dosing with 40 mg of esomeprazole under fasting and fed conditions. A model was applied in which the logistic function of %pH>4 was assumed to be linearly dependent on log-transformed AUC and C(max). The effects of repeated dosing and of fed relative to fasting conditions were included in the model, and the interindividual variation in %pH>4 was accounted for. RESULTS: The effect of the pharmacokinetic variables AUC and C(max) of esomeprazole on %pH>4 can be adequately described by a model using a logistic function for %pH>4 and a normally distributed error. In this model, log-transformed AUC and C(max) were both statistically significant. The model showed that for a fixed AUC, a decrease in C(max) gives an increase in %pH>4. A decrease in AUC, keeping C(max) fixed, gives a decrease in %pH>4, but a simultaneous decrease in C(max) and AUC will result in a less pronounced decrease in %pH>4. The model may be used for predicting differences in %pH>4 between two formulations, based on assessments of AUC and C(max). Repeated dosing gave an increased %pH>4, where approximately half of the increase stemmed from increased AUC and C(max), and the rest could be attributable to the persistent blockade of the proton pumps. Food intake reduced AUC and C(max) but had no obvious effect on %pH>4, which is explained by a prolonged time period with quantifiable plasma concentrations. CONCLUSION: The effect of the pharmacokinetic variables AUC and C(max) of esomeprazole on %pH>4 can be adequately described by a model using a logistic function for %pH>4 and a normally distributed error.

Administration, Oral↗

The effect of long-term microcrystalline chitosan therapy on plasma lipids and glucose concentrations in subjects with increased plasma total cholesterol: a randomised placebo-controlled double-blind crossover trial in healthy men and women.

OBJECTIVE: To evaluate the long-term effect of microcrystalline chitosan (MCC) on plasma lipids, especially the concentration of low-density lipoprotein (LDL) cholesterol, in subjects with a moderately increased concentration of plasma total cholesterol. METHODS: A total of 130 middle-aged men and women without severe disease and with a total cholesterol of 4.8-6.8 mmol/l and triglycerides below 3.0 mmol/l were randomised into two treatment groups. At the beginning of the 10-month trial, all participants received placebo 1.2 g twice daily during a 1-month run-in period. Subsequently, group 1 first received 1.2 g placebo twice daily for 3 months and then 1.2 g MCC twice daily for 3 months. Correspondingly, group 2 received 1.2 g MCC twice daily during the first and 1.2 g placebo twice daily during the second 3-month period. During the final 3-month follow-up period, both groups received MCC. Altogether, 83 participants completed the study. RESULTS: No difference was detected in the change in the LDL-cholesterol concentration between the treatments during the crossover trial ( P=0.98 for interaction between time period and treatment group, repeated-measures analysis of variance for crossover design). In an otherwise similar analysis, no differences were detected between the treatments in the concentrations of total cholesterol, high-density lipoprotein cholesterol, triglycerides and glucose. CONCLUSIONS: Treatment with MCC had no effect on the concentrations of plasma lipids or glucose in healthy middle-aged men and women with moderately increased plasma cholesterol concentrations.

Adjuvants, Pharmaceutic↗

The effectiveness of two oral contraceptives in suppressing plasma androstenedione, testosterone, LH, and FSH, and in stimulating plasma testosterone-binding capacity in hirsute women.

The effectiveness of two oral contraceptives in suppressing plasma androstenedione (A), testosterone (T), LH, and FSH and in stimulating testosterone-estradiol-binding globulin (TeBG) was evaluated in 39 hirsute women. Twenty-seven hirsute women received norethindrone 2 mg.-mestranol 0.1 mg. (Group I) and 12 received norgestrel 0.5 mg.-ethinyl estradiol 0.05 mg. (Group II). Hormone assays were performed before treatment and at the end of 3 weeks of therapy. Ninety percent of the women in both groups had an elevated plasma A and/or T. During treatment, plasma A,T, LH, and FSH were significantly reduced in both groups (p less than 0.01). In Group I, 78% of the women had a normal plasma A and T during treatment. In Group II, 83% of the women had a normal A and T during treatment. There was a greater increase in TeBG in Group I (p less than 0.01). It is concluded that these two oral contraceptives effectively suppressed the hyperandrogenism of most of the hirsute women.

Adolescent↗

The involvement of the plasma membrane in the development of Dictyostelium discoideum. I. Purification of the plasma membrane.

A method for the isolation and purification of plasma membranes of Dictyostelium discoideum by equilibrium centrifugation on sucrose followed by Renografin continuous density gradients has been developed and monitored both with electron microscopy and a number of enzyme assays. On electron microscopy, the final plasma membrane fractions are judged to be freethe basis of of nuclei, rough endoplasmic reticulum, lysosomes and peroxisomes. Some profiles of the mitochondrial inner membranes are found within the plasma membrane fractions, but this contamination has been estimated to be only 5%. On the basis on enzyme assays, the plasma membrane fractions contain all the 5'-nucleotidase activity in the final gradients and are free of catalase, acid phosphatase and malate dehydrogenase activity (markers for peroxisomes, lysosomes, soluble enzymes and the matrix of mitochondria). Their content of glucose-6-phosphatase is reduced by more than 70%. The large majority of RNA and DNA have been removed from the preparation.

Animals↗

Lymphocyte plasma membranes. VI. Plasma membrane glycoproteins of thymic and splenic lymphocytes from inbred rats.

Plasma membranes of splenic and thymic lymphocytes from ACI rats were analyzed for their protein and glycoprotein components by surface radioiodination with 125I and SDS-polyacrylamide gel electrophoresis. The glycoproteins were extracted with lithium diiodosalicylate, characterized and assayed with antisera to thymic antigen. Plasma membranes of both cell types showed more than 25 proteins of which 10--15 were glycoproteins. Both cells showed five major glycoproteins but their apparent molecular weights or intensities differed. Surface radioiodination showed a 120 000 daltons component, common to both cell types, and a 27 000 daltons thymus-specific component as the most exposed surface glycoproteins. Lithium diiodosalicylate extracts of the plasma membranes contained almost all of the glycoprotein components and comprised 5-6 percent of the total membrane protein and 40-50 percent of the total membrane carbohydrate, with sialic acid content in thymus twice that of the spleen cells. About 1 percent of the total plasma membrane protein and 7 percent of the total isolated glycoproteins from thymocytes were reactive with rabbit anti-rat thymocyte antiserum and the immune precipitates showed two components with apparent molecular weights of 72 000 and 27 000.

Animals↗

Origin and fate of rat plasma cholesterol in vivo. Modelling of cholesterol movements between plasma and organs.

A cholesterol system model was developed in the rat following a single injection of red cells containing free (unesterified) [3H]cholesterol. The radioactivity of free and esterified cholesterol in the different parts of the system was measured during the 48 h following tracer introduction. The model consisted of seven compartments (red cell free cholesterol, plasma and liver free and esterified cholesterol, total cholesterol in the rapidly and slowly exchangeable carcass pools). The model was validated by the similarity between simulated and experimental values during the 48 h following tracer introduction. Both the fractional rate of cholesterol esterification in the plasma (0.44 h-1) and liver (0.01 h-1) and the fractional exchange rate of free cholesterol from the plasma towards the various organs (particularly 3 h-1 towards the liver for a total of 7 h-1) can be estimated with this model. The results show that cholesterol movements between the plasma and the different organs take place mainly through intense free cholesterol exchanges, resulting in a low net flux.

Animals↗

Plasma estrogens and hepatic lipase in postheparin plasma with special reference to liver disease.

Hepatic lipase and lipoprotein lipase activity in postheparin plasma, plasma total estrogens (estradiol and estrone) and triglycerides were studied in patients with various liver disorders and in a reference group. The activity of hepatic lipase was not correlated to the estrogen level either in patients or in healthy controls. Peroral administration of estradiol valeriate to healthy females resulted, however, in a selective decline in hepatic lipase activity. A slight and not significant reduction was also observed in three infertile women after administration of follitropin (FSH) for a short period. The plasma concentration of estrogens did not correlate with the levels of plasma triglycerides and the relative content of triglycerides in low density lipoproteins either in patients or the controls. Lipase inhibition mediated by increase in estrogens therefore does not seem to exaplin the hypertriglyceridemia observed in patients with liver disease.

Adult↗

Comparison of the polypeptide composition of cystic fibrosis plasma with normal plasma by high resolution electrophoresis.

Cystic fibrosis and normal plasma proteins were compared by the method of high resolution two-dimensional electrophoresis in polyacrylamide gels. For the first dimension, samples were treated with urea and dithiothreitol and then subjected to isoelectric focusing in pH gradients of 3.5-10.0 or 5.0-8.0. The second dimension involved sodium dodecyl sulfate electrophoresis into gels of 10-20% polyacrylamide gradients. In one "blind" experiment, an attempt to segregate 12 plasma samples into six cystic fibrosis and six normals based on the polypeptide patterns was unsuccessful. Experiments using known cystic fibrotic and normal plasma samples (three further samples of each), depleted of albumin prior to electrophoresis, also failed to confirm the presence of cystic fibrosis related proteins or peptides. We have not been able to substantiate, by electrophoretic means, changes of sialic acid content of any plasma glycoprotein which might be expected to occur, for example, as a result of the postulated altered sialyltransferase activity in cystic fibrosis liver.

Blood Proteins↗

Growth-stimulatory action of plasma membrane-associated growth factor. A synergistic effect with platelet-poor plasma.

Growth factor activity was partially purified from mouse liver plasma membranes and its growth-stimulatory action on cultured mouse fibroblasts was studied. The plasma membrane-associated growth factor (PMGF) was unable to support the proliferation of mouse fibroblasts in monolayer when added as the sole source of growth factor. However, it stimulated the growth of fibroblasts in the presence of CM-Sephadex-treated human platelet-poor plasma (h-CMP) which by itself is not growth-stimulatory. The stimulation of DNA synthesis in quiescent fibroblasts was also observed upon the addition of PMGF and h-CMP. Under the same conditions, both platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) showed the same effect as did PMGF. The synergistic action of h-CMP with PMGF on quiescent cells was partially reproduced by insulin at microgram quantities or by insulin-like growth factor I(IGF-I) at nanogram quantities. Thus, the data presented here indicates that the action of PMGF is similar to that of the family of growth factors termed 'competence factor', and distinct from that of plasma growth factors termed 'progression factor'.

Animals↗

Correlation between endotoxin-neutralizing capacity of human plasma as tested by the limulus-amebocyte-lysate-test and plasma protein levels.

In the present study the endotoxin-neutralizing capacity of human plasma obtained from healthy volunteers was determined by use of the limulus-amebocyte-lysate test. The extent of the endotoxin-neutralizing capacity which showed a very broad variation was correlated to the plasma levels of some proteins which are believed to contribute to endotoxin transport and detoxification. The plasma levels of alpha 2-macroglobulin and transferrin, the major transport proteins, as well as the levels of IgG, IgA and IgM and apoprotein A were not significantly correlated to the neutralizing capacity. Only the apoprotein B, the major apoprotein of the low density lipoprotein fraction shows a significant correlation. Together with previously published results it should be concluded that low density lipoproteins are involved in the endogenous endotoxin-neutralizing reaction occurring in human plasma, at least when high doses of endotoxin are administered. Nevertheless the endotoxin-neutralizing reaction seems to be a very complex multistep process.

Apolipoproteins A↗

Plasma and testicular estradiol and plasma androgen profile in the male frog Rana esculenta during the annual cycle.

Seasonal plasma and testicular estradiol levels were measured in the male frogs, Rana esculenta, by radioimmunoassay. In plasma samples a simultaneous measurement of androgens was carried out in order to investigate a possible relationship between androgens and estradiol-17 beta. Concomitantly with the estradiol-17 beta peak in plasma and testes during the April-May period, plasma androgens sharply decreased.

Androgens↗

Somatostatin increases plasma T3 concentrations in Tilapia nilotica in the presence of increased plasma T4 levels.

An injection of ovine growth hormone, porcine follicle stimulating hormone, and bovine thyrotropin stimulating hormone increased in Tilapia nilotica plasma concentrations of thyroxine (T4) and reverse triiodothyronine (rT3) after 4 and 8 hr, whereas plasma concentrations of T3 were unaffected. An injection of somatostatin (SRIF) alone did not influence thyroid hormone levels. If, however, SRIF was injected together with these hormones, which raised plasma T4, or together with T4 itself, an increase in plasma concentrations of T3 could be observed, whereas the increase in rT3 was less pronounced. It is concluded that SRIF may change the normal 5-deiodinase (5-D) activity and increased rT3 during hyperthyroxinemia into a 5'-D activity and a rise in T3, respectively, in T. nilotica.

Animals↗