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Plasma phospholipid transfer protein. Adenovirus-mediated overexpression in mice leads to decreased plasma high density lipoprotein (HDL) and enhanced hepatic uptake of phospholipids and cholesteryl esters from HDL.

In vitro studies have shown that plasma phospholipid transfer protein (PLTP) converts isolated human high density lipoprotein-3 (HDL3) into larger HDL particles and generates lipid-poor apoA-I containing nascent HDL. To evaluate the role of PLTP in vivo we generated recombinant adenovirus vectors containing either human PLTP cDNA (rPLTP.AdV) or the reporter luciferase cDNA as a control. After intravenous infusion of 4 x 10(7) plaque-forming units (low dose) and 4 x 10(8) plaque-forming units (high dose) of rPLTP.AdV into mice, PLTP activity in plasma increased from base-line levels of 8.4 +/- 0.2 to 108 +/- 17 and from 8.9 +/- 0.6 to 352 +/- 31 micromol/ml/h, respectively, on day 4 (both p < 0.001). Thus, both low and high doses of rPLTP.AdV led to pronounced overexpression of human PLTP in mice. On day 4 after treatment, mice treated with low and high doses of rPLTP.AdV showed decreased HDL cholesterol (-54% and -91%) and apoA-I (-64% and -98%) (all p < 0.05). Kinetic studies revealed that the fractional catabolic rates of HDL labeled with [3H]phosphatidylcholine, [14C]phosphatidylcholine ether, [3H]cholesteryl ether, and 125I-labeled mouse apoA-I were increased by 8.5-, 8.7-, 3.8-, and 2.8-fold, respectively, in mice treated with low dose rPLTP.AdV (all p < 0.001). After injection of labeled HDL, mice treated with rPLTP.AdV showed an increased accumulation of labeled PC ether (+304%) and cholesteryl ether (+92%) in the liver (both p < 0.05). Two-dimensional gel electrophoresis of plasma 5 min after injection of HDL labeled with 125I-apoA-I demonstrated increased levels of newly generated pre-beta-HDL in mice overexpressing PLTP. In conclusion, HDL remodeling mediated by PLTP generates nascent, lipid-poor apoA-I in vivo and accelerates the hepatic uptake of HDL surface and core lipids in mice treated with rPLTP.AdV. Accelerated catabolism of HDL in mice overexpressing PLTP leads to low HDL levels. Our data indicate an important role for PLTP in modulating reverse cholesterol transport in vivo.

Adenoviridae↗

Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation.

S-Adenosylmethionine and S-adenosylhomocysteine (SAH), as the substrate and product of essential cellular methyltransferase reactions, are important metabolic indicators of cellular methylation status. Chronic elevation of SAH, secondary to the homocysteine-mediated reversal of the SAH hydrolase reaction, reduces methylation of DNA, RNA, proteins, and phospholipids. High affinity binding of SAH to the active site of cellular methyltransferases results in product inhibition of the enzyme. Using a sensitive new high pressure liquid chromatography method with coulometric electrochemical detection, plasma SAH levels in healthy young women were found to increase linearly with mild elevation in homocysteine levels (r = 0.73; p < 0.001); however, S-adenosylmethionine levels were not affected. Plasma SAH levels were positively correlated with intracellular lymphocyte SAH levels (r = 0.81; p < 0.001) and also with lymphocyte DNA hypomethylation (r = 0.74, p < 0.001). These results suggest that chronic elevation in plasma homocysteine levels, such as those associated with nutritional deficiencies or genetic polymorphisms in the folate pathway, may have an indirect and negative effect on cellular methylation reactions through a concomitant increase in intracellular SAH levels.

Adult↗

Plasma oestrogen and triglyceride concentrations and reproductive characteristics of broiler chickens after ten generations of selection at seven weeks of age for high or low plasma very low density lipoprotein concentration.

1. Day old female chicks from two lines of broilers, selected for high or low plasma concentrations of very low density lipoproteins, were fed ad libitum or restricted until point of lay. All birds were fed ad libitum after laying an egg, and aspects of growth and reproduction were measured to 40 weeks of age. 2. Compared with lean line birds the growth rate of fat line females fed ad libitum declined from 16 weeks of age. 3. Mortality from apparently stress-related causes in ad libitum fed fat line females increased from 16 weeks of age and was 71% overall, compared with 26% in ad libitum fed lean line females. Mortality in the corresponding restricted birds was 20% and 7%, respectively. 4. Few fat line females fed ad libitum commenced lay and those which were restricted during rearing stopped laying after the initiation of ad libitum feeding. Egg productions in lean line birds fed ad libitum or restricted were similar. 5. Fat line females fed ad libitum had few yellow follicles and a high rate of atresia at first egg and between 37 and 39 weeks, as did restricted fat line birds between 37 and 39 weeks of age after being fed ad libitum. 6. Plasma concentrations of oestradiol-17 beta were 5-fold higher in fat compared with lean line females at 35 weeks of age. There was a similar large difference in concentrations of plasma triglyceride which reached 59 mg/ml in fat line females fed ad libitum.

Age Factors↗

Renin stimulation by passive tilting: the influence of an anti-gravity suit on postural changes in plasma renin activity, plasma noradrenaline concentration and kidney function in normal man.

Plasma renin activity (PRA), plasma noradrenaline concentration, heart rate, blood pressure, and clearances of para-aminohippurate and inulin were measured in twelve normal subjects (clearances in only three subjects) before and after 40 min of 60 degrees upright tilting. The tilting experiments were repeated after inflation of an anti-gravity suit to 60 mmHg on the lower extremities. Inflation of the anti-gravity suit caused an abolition of the postural PRA increase, a marked reduction of the postural increases in plasma noradrenaline and heart rate, and elimination of the decreases in pulse pressure, inulin and para-aminohippurate clearances and sodium excretion. The results suggest a decisive role of the sympathetic nervous system for postural renin increase, probably mainly activated by stretch receptors in the low-pressure cardiopulmoanry area.

Adult↗

The gamma-trace concentration of normal human seminal plasma is thirty-six times that of normal human blood plasma.

Fresh human seminal plasma was demonstrated to contain a basic microprotein with the same size, electrophoretic mobility, isoelectric point and immunochemical properties as isolated human gamma-trace. The concentration of gamma-trace in 24 normal seminal plasma samples was found to be (mean +/- SD): 51 +/- 8.1 mg/l which is 36 times higher than the normal human blood plasma concentration of gamma-trace.

Adult↗

Use of plasma for immediate diagnosis of multiple sclerosis (plasma-erythrocyte unsaturated fatty acid test): comparison with the erythrocyte-unsaturated fatty acid (E-UFA) test.

A labile factor in plasma (but not serum) of MS subjects confers MS like properties vis à vis effect of linoleic acid (LA) and arachidonic acid (AA), on the electrophoretic mobility of washed red blood cells (RBC) irrespective of their provenance. Plasma from anomalous MS relatives and other neurological diseases (OND) likewise confer corresponding properties on washed RBC. The magnitude of results produced by LA and AA on plasma coated cells is equal to that produced by LA and AA directly on the original cells and approximately twice that reported with latex particles.

Arachidonic Acid↗

Time since menopause does not affect plasma viscosity, plasma thromboxane levels and Doppler findings.

OBJECTIVES: To evaluate whether the use of transdermal hormone replacement therapy (HRT), in women within 5 years of menopause compared with women who were postmenopausal for > 5 years, would significantly influence thromboxane B2 levels, plasma viscosity and Doppler flow parameters at the level of the uterine, internal carotid, ophthalmic and bladder wall arteries. METHODS: Thirty-five normal-weight (body mass index > 19 and < 25 kg/m(2)) postmenopausal women (age 54.6 +/- 3.9 years, mean +/- standard deviation) participated in the study and were divided into two groups (Group I: n = 19, time since menopause < 5 years; and Group II: n = 16, time since menopause > 5 years). Patients were treated with a continuous estradiol transdermal supplementation and 12-day courses of medroxyprogesterone acetate every 2 months. They were studied at baseline and after 6 months (in the estrogen-only phase of the cycle). RESULTS: Results showed a beneficial effect of hormone substitution after 6 months of therapy. Baseline plasma viscosity was similar in both groups, and decreased significantly after therapy in both Group I (-17.5%) and Group II (-15.6%). Plasma levels of thromboxane B(2) were similar at baseline and diminished equally in Group I and Group II (-85.6% and -85.2%, respectively) after treatment. Doppler assessment of the pulsatility index at the level of uterine, internal carotid, ophthalmic and bladder wall arteries showed no differences between groups at baseline and revealed a significant reduction of vascular impedance at the end of the treatment in both groups. CONCLUSIONS: Time since menopause does not affect the potential hemodynamic benefits of HRT in normal-weight women.

Blood Viscosity↗

Establishment of plasma membrane domains in hepatocytes. I. Characterization and localization to the bile canaliculus of three antigens externally oriented in the plasma membrane.

A membrane fraction denoted N2 upper was isolated from homogenates of rat liver by sucrose gradient centrifugation. This fraction, which was enriched 65-fold over the homogenate in 5'-nucleotidase activity, was used as an immunogen in goats. The antisera obtained contained antibodies to three predominant polypeptides in the N2 upper membrane fraction, as shown by crossed immunoelectrophoresis. These polypeptides had molecular weights of 105,000, 110,000, and 160,000 after recovery from the crossed immunoelectrophoretic gels and are denoted PM105, PM110, and PM160. Each was a distinct polypeptide, as shown by the distinct peptide patterns resulting from limited proteolysis in the presence of detergents. The three polypeptides were synthesized by primary cultures of hepatocytes and were externally oriented at the surface of these cells, as shown by their accessibility in situ to iodination catalyzed by lactoperoxidase. They were not detectable in the serum by crossed immunoelectrophoresis. The three antigens were present at very low (PM110) or nondetectable (PM105, PM160) concentrations in intracellular membrane fractions derived from the Golgi and smooth and rough endoplasmic reticulum of liver. The antigens also were reduced in concentration in a plasma membrane fraction most likely derived from the sinusoidal surface of the hepatocyte. The three membrane antigens bind to concanavalin A; hence, they are probably glycoprotein constituents of a discrete domain of the hepatocyte plasma membrane. Immune complexes were isolated after crossed immunoelectrophoresis and injected into rabbits. Each of the antisera obtained was reactive to one of the membrane polypeptides. Sections of fixed rat livers were reacted with each of the antibodies and then the primary antibody was localized by indirect immunocytochemical methods using horseradish peroxidase or colloidal gold as labels. Each of the three antigens was localized by this method to the bile canalicular domain of the hepatocyte plasma membrane.

Animals↗

Synthesis of all plasma protein fractions except gamma globulins by the liver; the use of zone electrophoresis and lysine-epsilon-C14 to define the plasma proteins synthesized by the isolated perfused liver.

Lysine-epsilon-C(14)-labeled plasma proteins produced by the normal rat and the isolated perfused rat liver have been fractionated by preparative zone electrophoresis. The isolated perfused liver incorporates lysine-epsilon-C(14) into the plasma albumin, alpha globulin, and beta globulin (including fibrinogen) fractions. No significant C(14) incorporation into the trichloracetic acid-precipitable proteins of the gamma globulin fraction was observed. Presumptive evidence indicates that the alpha globulins turn over more rapidly than any other major plasma protein fraction. The increased production of gamma globulins in liver disease is discussed.

Animals↗

Relationship between V3 sequences of HIV type 1 from plasma, T cells, and dendritic cells suggests that plasma virus may arise from different cell sources.

Nucleotide sequences of HIV-1 from plasma virus RNA and proviral DNA extracted from blood dendritic cells (DCs) and from T cells were analyzed to determine whether blood DCs may harbor a restricted population of virus variants. The sequence of the V3 loop and 51 bases from the 3' flanking region were determined in four patients not receiving antiviral therapy. There was no evidence of a unique or more restricted population of variants in DCs for any of the four patients studied. However, for one patient there was evidence of differences between plasma virus and virus in the T cell population, with virus in the plasma showing a closer relationship to DC-derived sequences.

Amino Acid Sequence↗

Plasma lecithin-cholesterol acyltransferase activity and plasma lipoprotein composition and concentrations in kwashiorkor.

Plasma lecithin-cholesterol acyltransferase (LCAT) activity, lipoprotein composition, and lipoprotein concentrations were measured in 21 children with kwashiorkor before (day 1), during (day 10), and after treatment (day 30). Day 1 LCAT activity (78.2 mumol.L-1.h-1) was decreased with respect to day 10 (139.2 mumol.L-1.h-1, P less than 0.001) and day 30 (108.0 mumol.L-1.h-1, P = 0.08). Plasma total cholesterol (TC), cholesterol ester (CE), and lipoprotein CEs (VLDL, IDL, LDL, and HDL) were reduced relative to days 10 and 30 (P less than 0.001). Before treatment HDL composition was abnormal. On days 1, 10, and 30, the respective mean HDL-apolipoprotein A-I (apo A-I) concentrations were 23.33, 39.66, and 36.08 mumol/L. LDL-apo B concentrations were 0.40, 0.68, and 0.56 mumol/L (P less than 0.01, days 10 and 30 vs day 1). LDL particles on day 1 were decreased in number, depleted of CE, and laden with triacylglycerol and surface lipids. LCAT activity on day 1 correlated with LDL-CE linoleate (P less than 0.05, r = 0.48). Reduced plasma LCAT activity is an important factor related to abnormalities in lipoprotein composition and concentrations.

Apolipoproteins B↗

Short-term plasma renin activity suppression by saline and release of a plasma endogenous Na/K ATPase inhibitor in essential hypertension.

The present study was conducted in 15 essential hypertensives to evaluate the modifications of plasma levels of an endogenous Na/K ATPase inhibitor, blood pressure, forearm hemodynamics and plasma renin activity (PRA) elicited by an intravenous saline infusion (0.9% NaCl at the mean rate of 0.22 mL/min/kg body weight for 2 h). The response to saline was determined in the whole hypertensive population as well as in two subgroups of patients classified according to their rate of PRA suppression in response to volume expansion by comparison with normotensive controls (Normal- and Low-suppressors: N-S, L-S). Over the whole group of hypertensive patients, NaCl load provoked an increase in Na/K ATPase inhibitory activity, measured by enzyme-coupled assay, which was linearly related to PRA decline (r = 0.73) and to the increase in mean blood pressure (r = 0.57). These effects were clearly enhanced by considering L-S patients alone. Urinary Na/K ratio after saline infusion was significantly higher in L-S as result of a lesser potassium excretion in this subgroup. Our results support the hypothesis that acute volume expansion with saline causes an increase in plasma levels of an endogenous sodium pump inhibitor with hemodynamic effects and whose release is related to the individual handling of infused fluids and to the degree of renin-angiotensin-aldosterone suppression.

Adult↗

Taurine transport across hepatocyte plasma membranes: analysis in isolated rat liver sinusoidal plasma membrane vesicles.

To elucidate the mechanism of taurine transport across the hepatic plasma membranes, rat liver sinusoidal plasma membrane vesicles were isolated and the transport process was analyzed. In the presence of a sodium gradient across the membranes (vesicle inside less than vesicle outside), an overshooting uptake of taurine occurred. In the presence of other ion gradients (K+, Li+, and choline+), taurine uptake was very small and no such overshoot was observed. Sodium-dependent uptake of taurine occurred into an osmotically active intravesicular space. Taurine uptake was stimulated by preloading vesicles with unlabeled taurine (transstimulation) in the presence of NaCl, but not in the presence of KCl. Sodium-dependent transport followed saturation kinetics with respect to taurine concentration; double-reciprocal plots of uptake versus taurine concentration gave a straight line from which an apparent Km value of 0.38 mM and Vmax of 0.27 nmol/20 s x mg of protein were obtained. Valinomycin-induced K+-diffusion potential failed to enhance the rate of taurine uptake, suggesting that taurine transport does not depend on membrane potential. Taurine transport was inhibited by structurally related omega-amino acids, such as beta-alanine and gamma-aminobutyric acid, but not by glycine, epsilon-aminocaproic acid, or other alpha-amino acids, such as L-alanine. These results suggest that Na+-dependent uptake of taurine might occur across the hepatic sinusoidal plasma membranes via a transport system that is specific for omega-amino acids having 2-3 carbon chain length.

Animals↗

Effect of risperidone on plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels in schizophrenic patients: relationship among plasma concentrations of risperidone and 9-hydroxyrisperidone, pMHPG levels, and clinical improvement.

We examined the relationships among the clinical efficacies of risperidone, plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, and changes in plasma free MHPG (pMHPG) in 14 schizophrenic patients. Clinical improvement in negative symptoms of schizophrenia treated with risperidone has been associated with increased pMHPG and, in the present study, there were positive correlations between plasma 9-hydroxyrisperidone concentrations and increased pMHPG levels. These results suggest that risperidone might improve negative symptoms in schizophrenia by influencing noradrenergic neurons.

Adolescent↗

Effects of converting enzyme inhibition on blood pressure, plasma renin activity (PRA) and plasma aldosterone in hypertensive diabetics compared to patients with essential hypertension.

Hypertension with diabetes mellitus has been associated with suppression of the renin-angiotensin-aldosterone system. We have studied the effects of the converting enzyme inhibitor, captopril, on blood pressure, plasma renin activity (PRA) and plasma aldosterone in 10 stable hypertensive diabetic subjects and 10 age-matched patients with essential hypertension. There was no clinical evidence of complication in the diabetic subjects and their diabetic treatment remained unchanged throughout the study. Mean captopril doses used were similar in both groups. In the diabetics and the essential hypertensives, treatment resulted in a significant and similar decrease in blood pressure. Pre-treatment basal and stimulated PRA and the change of PRA with captopril were also similar. Pre-treatment stimulated plasma aldosterone and the response of aldosterone to postural stress was significantly lower in the diabetic group, suggesting an impaired adrenal responsiveness to stress. Despite this, our findings indicate that the hypotensive action of captopril is at least as effective in hypertension associated with otherwise uncomplicated diabetes mellitus as in essential hypertension.

Aldosterone↗

Menstrual cycle and ovarian hormone effects on plasma and platelet monoamine oxidase (MAO) and plasma dopamine-beta-hydroxylase (DBH) activities in the rhesus monkey.

Dopamine-B-hydroxylase (DBH) and monoamine oxidase (MAO) in plasma and platelets were studied in six female rhesus monkeys during three complete menstrual cycles. The same monoamine enzymes of seven bilaterally ovariectomized females were compared with a group of controls. A difference was found in platelet MAO between a mid-menstrual-cycle peak and a perimenstrual trough in these animals, while plasma MAO was unchanged. DBH showed an inverted cyclical variation to that demonstrated by platelet MAO. The ovariectomized females showed significant differences from the controls, confirming the effects of the ovarian sex steroid hormones on platelet MAO and plasma DBH. The variation in these peripheral enzymes may be reflective of changes in brain monoamine systems, which may play some role in the behavioral changes observed during the menstrual cycle in primates.

Animals↗

The effects of testosterone on plasma and platelet monoamine oxidase (MAO) an plasma dopamine-beta-hydroxylase (DBH) activities in the male rhesus monkey.

Dopamine-beta-hydroxylase (DBH) and monoamine oxidase (MAO) in plasma and platelets were studied in male rhesus monkeys to evaluate the effects of changes in endogenous testosterone on the activity of these enzymes. High plasma testosterone concentrations attained at the end of the mating season were associated with relatively low levels of platelet MAO activity. When testosterone levels fell, platelet MAO increased significantly. Mean differences in platelet MAO activity between a group of castrated and control males were in the direction expected, with the highest MAO activity in the castrated monkeys, but these differences did not attain statistical significance. No significant mating season or castration effects were seen in plasma DBH or MAO enzyme activities. These data support the hypothesis of a link between testosterone and some monoamine systems, and possibly the monoamine-related behaviors linked to testosterone in primates.

Animals↗

Plasma assay of salbutamol by means of high-performance liquid chromatography with amperometric determination using a loop column for injection of plasma extracts. Application to the evaluation of subcutaneous administration of salbutamol.

An isocratic high-performance liquid chromatography method with amperometric detection for the assay of plasma salbutamol is described. The plasma extract is injected into the chromatographic system via a loop column. This insures the purification of the injected extracts and allows a simple and rapid liquid-solid extraction procedure. The good reliability, as shown by the low limit of detection (0.5 ng/ml) and a precision ranging between 5 and 10%, has permitted the investigation of a new mode of administration of salbutamol using a portable subcutaneous infusion pump. Our results show that subcutaneous administration yields plasma levels comparable with those obtained after usual intravenous doses.

Albuterol↗