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PubMed1983

Sequential changes in plasma renin activity and plasma catecholamines in mildly hypertensive patients during acute, furosemide-induced body-fluid loss.

To evaluate the role of adrenergic mechanisms in the acute response of renin to furosemide, plasma renin activity (PRA) and plasma catecholamine concentrations were measured for 3 h after i.v. administration of furosemide 1 mg/kg to 8 patients with mild essential hypertension. Furosemide induced a prompt and long-lasting increase in renin, with PRA more than doubled at all times. The increase in PRA within the first 30 min paralleled the peak increases in urinary water and sodium flow rates, and significant decreases in plasma volume and central venous pressure. There was no change in plasma catecholamine concentrations. Plasma noradrenaline was increased significantly at 60 min and adrenaline at 90 min, once furosemide had induced a marked loss of body-fluid and approximately 65% decrease in central venous pressure. Both catecholamines remained elevated until the end of the study, whereas urinary water and sodium flow rates had returned to their pre-treatment values by 150 min. Mean blood pressure was essentially unchanged throughout the study, whereas heart rate increased significantly after 90 min. The findings suggest that in mildly hypertensive patients adrenergic mechanisms are not involved in the initial renin response to furosemide, but they come into play later, probably as a result of reflex sympathetic activation triggered by marked volume depletion.

Adult↗
PubMed1979

Comparison of phenytoin determinations in plasma, plasma dialysate and saliva for control of antiepileptic therapy in children.

Phenytoin was determined in plasma or serum, dialysate from plasma or serum and saliva in 45 children and 7 adults by gas chromatography. 200 microliter of plasma were necessary for dialysis. Close correlations were found between phenytoin concentrations in the different media (r greater than or equal to 0.95). Since in some cases the levels in saliva were extremely high in comparison to plasma and dialysate, precautions are advisable when using phenytoin determinations in saliva for therapeutic decisions. Clinical data from 15 children with high phenytoin levels suggest that there is no advantage in determining the unbound fraction of the drug in plasma for the control of antiepileptic therapy.

Adolescent↗
PubMed1984

Characteristic features of plasma amino acid, plasma pancreatic glucagon, serum insulin concentrations in cirrhotic patients with histories of chronic alcohol consumption.

Plasma amino acid, plasma pancreatic glucagon and serum insulin levels were simultaneously measured in cirrhotic patients with (drinkers) and without a history of alcohol drinking (non-drinkers), as compared to those in alcoholics without liver disease. Clinical characteristics in drinkers and non-drinkers, such as the extent of liver dysfunction, which may affect plasma amino acid levels, were strictly matched. Plasma pancreatic glucagon levels in the drinker group were much higher than those in the non-drinker group. In the former group, the elevated plasma pancreatic glucagon levels were correlated (p less than 0.05) to total amino acid levels (the sum of 20 kinds of L-amino acid concentrations) and, elevated AAA concentrations leading to a diminished BCAA/AAA ratio. Drinkers with histories of hepatic encephalopathy presented grossly elevated glucagon levels and severely abnormal aminograms similar to those observed in hepatic insufficiency.

Adult↗
PubMedDate not supplied

Rapid determination of functional liver plasma flow in ICU patients by a modified hepatic D-sorbitol plasma clearance method.

Changes in liver perfusion may have a substantial influence on the pharmacokinetics of drugs with flow-controlled metabolism. This may have important implications for drug dosage in patients in an intensive care unit (ICU). The hepatic D-sorbitol plasma clearance has been suggested as a non-invasive test for evaluating functional liver plasma flow, which is in reasonable agreement with the direct blood measurement. However, its determination requires D-sorbitol infusion for 3 h or administration of a D-sorbitol bolus and withdrawal of blood specimens every 3-5 min. Since both variants are impractical in the ICU setting, a bolus/infusion technique was tested. A combined technique applying a bolus (0.85 mg/kg) and steady-state infusion (0.0014 mg/kg/min) of D-sorbitol was tested in 10 ICU patients without hepatic disease (group 1) and in 10 ICU patients with liver disease (group 2). Steady-state plasma levels (+/- 9%, P < 0.05) could be achieved within 60 min in all patients. The modified D-sorbitol clearance method requires a bolus and an infusion of D-sorbitol and withdrawal of a single blood specimen after 60 min. The lowest values of functional liver plasma flow were determined in patients with decompensated liver cirrhosis, acute fatty degeneration of the liver or Budd-Chiari syndrome. The method for routine determination of functional hepatic plasma perfusion proved to be rapid, safe and non-invasive in ICU patients. Hepatic D-sorbitol clearance may be especially useful for assessing the functional aspect of liver perfusion.

Adult↗
PubMed2003

Identification and purification from the plasma of Type 1 diabetic subjects of a proteolytically active Grp94Evidence that Grp94 is entirely responsible for plasma proteolytic activity.

AIMS/HYPOTHESIS: The overall increase in proteolytic activity in diabetes is known to be associated with the development and progression of vascular complications. Our aim was to investigate in detail the molecular nature of this activity in the plasma of Type 1 diabetic subjects. METHODS: Plasma of both diabetic and control subjects was subjected to various purification procedures (ion exchange and affinity chromatography, HPLC, immunoprecipitation, electrophoresis, immunoblot and mass analyses) to identify the proteins of interest. Biological activities were measured on specific substrates. RESULTS: In diabetic but not normal plasma we identified the presence of two heat shock proteins, Grp94 (Glucose-regulated protein94) and HSP70. The higher-than-normal proteolytic activity of Grp94 was: (i) directed against casein, but not against endogenous plasma proteins; (ii) fully and specifically inhibited only by anti-Grp94 polyclonal antibodies; and (iii) coupled with low-level ATPase activity. In addition, ATP binding to Grp94 was able to modulate proteolytic activity. We found that Grp94 in plasma circulates only as high molecular mass homo- and hetero-complexes, the latter mostly formed with IgG to which Grp94 is also linked by tenacious binding. Proteolytically-active Grp94 was purified by immunoprecipitation, which co-immunoprecipitated alpha(1)antitrypsin. CONCLUSION/INTERPRETATION: Our results show the unexpected extracellular location and characteristic biological function of Grp94 even at a late stage of disease. These findings have physiopathological relevance for predicting activation of both autoimmune and inflammatory processes potentially associated with vascular complications.

Adult↗
PubMed1996

Cd2+-induced damage to yeast plasma membrane and its alleviation by Zn2+: studies on Schizosaccharomyces pombe cells and reconstituted plasma membrane vesicles

In Schizosaccharomyces pombe, Cd2+ shares the same uphill uptake system with Zn2+. Both heavy metals inhibited growth, respiration, H+/glucose uptake, and glucose-induced proton extrusion, Cd2+ being a 10-15-fold stronger inhibitor. In contrast, both had a similar effect on the plasma membrane H+-ATPase, enhancing its affinity for ATP and reducing the rate of ATP splitting. Cd2+ caused protracted strong fluidization of the plasma membrane of energized cells, whereas deenergized cells, phosphatidylcholine liposomes, and plasma membrane fragments, either purified or incorporated into the liposomes, exhibited only a short initial fluidization. Zn2+, which caused only a marginal membrane fluidization, suppressed the fluidizing action of Cd2+. The fluidizing effect of both heavy metals on liposomes was reduced by the presence of plasma membrane fragments in the liposome membrane. At 50 &mgr;M, Cd2+ brought about loss K+ (18 K+/1 Cd2+) from energized, but not from deenergized cells since Cd2+ must first accumulate in the cells before causing a detectable effect. A simple membrane disruption by external Cd2+ is, therefore, unlikely to be the main mechanism of cadmium-induced potassium loss in intact cells. Zn2+ had virtually no effect below 1 mM concentration, and it again weakened the K+-releasing effect of Cd2+. Cd2+ caused a strong loss of K+ also from K+-containing liposomes, probably because of a direct interaction with liposome phospholipids. Incorporation of plasma membrane fragments into the liposomes reduced the K+ loss sixfold.

Journal Article↗
PubMed2002

Determination of total platinum in plasma and plasma ultrafiltrate, from subjects dosed with the platinum-containing N-(2-hydroxypropyl)methacrylamide copolymer AP5280, by use of graphite-furnace Zeeman atomic-absorption spectrometry.

AP5280 is an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer to which are linked tetrapeptide side chains containing bioactive platinum complexes at their C-terminal sides. We have developed and validated a rapid and sensitive analytical assay for the determination of total platinum concentrations in plasma, and free platinum of an AP5280 origin in plasma ultrafiltrate (PUF), of subjects dosed with AP5280. The total platinum levels were determined by use of graphite-furnace atomic-absorption spectrometry (GF-AAS) with Zeeman correction after appropriate dilution of the plasma sample with plasma-hydrochloric acid 0.2 mol L(-1) (1:5) as diluent. The limit of quantitation of this assay is 0.25 micromol L(-1) platinum in plasma. Linear calibration curves were obtained over the concentration range 0.25-5.0 micromol L(-1). Accuracy was between 87.7% and 104.2% and precision was 15.3% at the lowest concentration and less than 14% for all other levels tested. Accuracy and precision were thus in accordance with generally accepted criteria for analytical methods. Analysis of samples obtained from patients receiving AP5280 demonstrated the applicability of the described assay. Analysis of free platinum in PUF was performed by use of a previously validated and reported assay from our institute in which the same instrumental method is used.

Acrylamides↗
PubMed1997

Disopyramide concentrations in human plasma and saliva: comparison of disopyramide concentrations in saliva and plasma unbound concentrations.

OBJECTIVE: This study was performed to investigate whether it is possible to use saliva instead of blood usually used for therapeutic drug monitoring (TDM) of disopyramide. METHODS: Six healthy male volunteers ingested 200 mg of disopyramide base, and the disopyramide concentrations in saliva and plasma (total and unbound) were determined by the HPLC. RESULTS: Disopyramide concentration-time profiles for the saliva were nearly equal to those for the plasma unbound concentrations. A large variation for absorption time of the drug was observed among the subjects. Disopyramide concentrations (Cs) in saliva did not correlated well with plasma total concentrations (Cp), r = 0.799, but did well with unbound concentrations (Cpu), r = 0.969, for the 3-12 h period on the elimination phase. The mean ratio of disopyramide concentrations in the saliva against the plasma unbound concentrations was almost constant (1.02(0.10), CV = 9.7%) for the period. The pharmacokinetic parameters (tmax, t1/2, AUC, AUMC and MRT values) for disopyramide calculated from the saliva data were nearly equal to those from the unbound data. CONCLUSION: Disopyramide concentrations in saliva correlated well with plasma unbound concentrations on the elimination phase.

Adult↗
PubMed1996

Comparison of ethanol plasma-protein precipitation with plasma ultrafiltration and trichloroacetic acid protein precipitation for the measurement of unbound platinum concentrations.

Sample preparation for the measurement of non-protein-bound platinum was evaluated by precipitation of plasma proteins with cold ethanol. The method was compared with the routinely used plasma ultrafiltration and with trichloroacetic acid (TCA) protein precipitation. After incubation of human plasma samples with cisplatin or carboplatin, unbound platinum concentrations were determined applying Amicon Diaflo ultrafiltration membranes and Millipore ultrafree-MC filters. For protein precipitation, 1 ml of cold (-20 degrees C) pure ethanol was added to 0.5 ml of human plasma and the supernatant was collected after 2 h, or 0.5 ml of cold 20% TCA was added to 0.5 ml of plasma. Platinum was analyzed by atomic absorption spectrophotometry (AAS). There was no significant difference between the ethanol and ultrafiltration methods in the unbound platinum concentration. The protein content in the supernatant (1.00 +/- 0.20%) was slightly higher than that in the Amicon (0.58 +/- 0.05%) and Millipore (0.55 +/- 0.04%) ultrafiltrates. On average, the TCA and ethanol method seemed to be equally appropriate. The ethanol precipitation method is concluded to be simple, convenient, and reproducible and has negligible costs.

Blood Proteins↗
PubMed2006

Response of plasma and gastrointestinal melatonin, plasma cortisol and activity rhythms of European sea bass (Dicentrarchus labrax) to dietary supplementation with tryptophan and melatonin.

Melatonin is an effective antioxidant, immunostimulant, gonadal maturating regulator and antistress indoleamine that may be potentially useful for fish farmers. We have explored two possible ways of increasing plasma melatonin levels through the diet: direct melatonin supplementation (ME diet) and supplementation with the melatonin precursor tryptophan (TRP diet). To this end, a group of sea bass was fed a commercial diet (STD diet) at a regular time for 16 days, after which plasma, intestine, and bile samples were taken at four different time points: 120 min before, and 15, 180 and 480 min after feeding. Locomotor activity, intestinal and biliary melatonin, and plasma melatonin, serotonin and cortisol levels were measured. This same sampling process and analyses were also carried out after feeding sea bass TRP diet or ME diet for 1 week. Our results show that melatonin, but not tryptophan supplementation of the diet increases plasma, intestine and bile levels of melatonin. Plasma serotonin levels, on the other hand, were increased by dietary tryptophan, but not by melatonin, confirming the availability of supplemented tryptophan for serotonin synthesis. Both treatments were equally effective in reducing the high cortisol levels observed with the STD diet.

Animals↗
PubMed2003

High plasma level of asymmetric dimethylarginine in patients with acutely exacerbated congestive heart failure: role in reduction of plasma nitric oxide level.

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is elevated in congestive heart failure (CHF) concomitantly with the higher levels of nitric oxide (NO) and cytokines. We investigated the association among ADMA, NO, and cytokines in human CHF. Blood was collected from 25 patients with acutely exacerbated chronic CHF (acute CHF, mean age 61 +/- 3 years), 23 patients with chronic compensated CHF (chronic CHF, mean age 62 +/- 2 years), and 26 control subjects (mean age 51 +/- 1 years). ADMA was measured by high-performance liquid chromatography. Tumor necrosis factor-alpha (TNF-alpha) was measured by enzyme-linked immunosorbent assay. Nitrate plus nitrite (NOx) was measured by the Griess method. The plasma levels of ADMA and TNF-Alpha were higher in patients with acute CHF than in those with chronic CHF and control subjects (both P < 0.05). The plasma level of NOx was higher in patients with chronic CHF than in those with acute CHF and control subjects (both P < 0.01). The plasma level of TNF-Alpha was positively correlated with that of ADMA in combination with patients with acute and chronic CHF (r = 0.31, P < 0.01). The plasma level of ADMA was, furthermore, negatively correlated with that of NOx (r = -0.29, P < 0.05). These findings indicate that ADMA is related to exacerbation of chronic CHF by suppression of the compensatory higher level of plasma NO.

Acute Disease↗
PubMed2006

Relation of plasma homocysteine to plasma amyloid beta levels.

BACKGROUND: Elevated plasma homocysteine and amyloid beta (Abeta) have been associated with Alzheimer's disease (AD). We investigated the cross-sectional association between these biomarkers. METHODS: We used linear regression to relate plasma homocysteine and Abeta adjusting for age, gender, creatinine, APOE-epsilon4, and ethnic group in 327 persons aged 78 +/- 6.6 years. RESULTS: Plasma homocysteine correlated with age, serum creatinine, plasma Abeta40 and Abeta42, and was inversely correlated with serum vitamin B12, and folate. Abeta42, but not Abeta40, was related to later development of dementia. Homocysteine was related to higher Abeta40 levels (coefficient = 2.0; P < 0.0001) and this association was attenuated after adjustment for creatinine (coefficient = 1.0; P < 0.0001). The crude association between homocysteine and Abeta42 was weaker (coefficient = 0.5; P = 0.01) and became non-significant after adjustment for creatinine (coefficient = 0.4; P = 0.06). These associations were unrelated to ethnicity, the presence of APOE-epsilon4 or dementia. Analyses by quartiles of homocysteine showed that these association were driven primarily by the fourth quartile. CONCLUSIONS: Plasma homocysteine is directly related to Abeta40. The association with Abeta42 is not significant. These results seem to indicate that homocysteine is related to aging but not specifically to AD.

Aged↗
PubMed2002

Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile.

Pycnogenol (PYC), an extract of French maritime pine bark (Pinus pinaster), is a potent antioxidant with potential health benefits. Its bioavailabilty has previously been shown by urinary excretion studies of constituents and metabolites of PYC. The aim of this study was to test the effect of PYC supplementation on measures of oxidative stress and the lipid profile in humans. Twenty-five healthy subjects received PYC (150 mg/d) for 6 wk. Fasting blood was collected at baseline, after 3 and 6 wk of supplementation, and again after a 4-wk washout period. After 6 wk of supplementation with PYC, a significant increase in plasma polyphenol levels was detectable, which was reversed after the 4-wk washout phase. The antioxidant effect of PYC was demonstrated by a significant increase in oxygen radical absorbance capacity (ORAC) in plasma throughout the supplementation period (P < 0.05). The ORAC value returned to baseline after the 4-wk washout period. Moreover, in addition to its antioxidant effects, PYC significantly reduced LDL-cholesterol levels and increased HDL-cholesterol levels in plasma of two-thirds of the subjects. While the LDL changes reversed during washout, the HDL increase did not. There was no significant difference in LDL oxidizability or plasma lipid peroxides following PYC supplementation. Hence, following oral supplementation in humans, PYC significantly increases antioxidant capacity of plasma, as determined by ORAC, and exerts favorable effects on the lipid profile.

Administration, Oral↗
PubMed1977

d-Norgestrel concentrations in maternal plasma, milk, and child plasma during administration of oral contraceptives to nursing women.

In order to correlate plasma and milk concentrations of d-norgestrel (d-Ng) in lactating women, three oral contraceptives, containing different amounts of this synthetic gestagen, were given to 15 fully lactating women, starting two months post partum. Plasma and milk samples were collected according to a special schedule. d-Ng concentrations in plasma and milk were measured by radioimmunoassay. When d-Ng was measured in milk, extraction was performed with petroleum ether and in the radioimmunoassay an internal standard was used. This method is evaluated in the present paper. The plasma: milk ratio of d-Ng was found to be about 100:15 and the amounts of d-Ng transferred with 600 ml. of milk per day were calculated to be 0.3 an 0.15 microgram with daily intakes of 250 and 150 microgram of d-Ng, respectively, corresponding to about 0.1 per cent of the given dose. When the women received 30 microgram of d-Ng daily, no d-Ng could be detected in the milk. In three of the breast-fed children the d-Ng concentration in plasma was measured. This concentration was found to be in the same range as would be expected after oral d-Ng medication to adults, allowing for body weight differences, indicating that d-Ng is metabolized and is not accumulated in the baby.

Contraceptives, Oral↗
PubMed1981

The relationship between plasma membrane lipid composition and physical-chemical properties. II. Effect of phospholipid fatty acid modulation on plasma membrane physical properties and enzymatic activities.

The fatty acid composition of plasma membrane phospholipids of the murine T lymphocyte tumor EL4 were systematically modified in an attempt to understand the relationship between lipid bilayer composition and plasma membrane physical and biological properties. Two plasma membrane enzyme activities, adenylate cyclase and ouabain-sensitive (Na+ + K+)-ATPase, were measured in normal and fatty acid-substituted EL4 plasma membrane fractions. The fatty acid effect on enzyme activities was similar to previously reported effects of fatty acids on cytotoxic T cell function. The activity of both enzymes was inhibited by saturated fatty acids, while unsaturated fatty acids had a moderate enhancing effect on both enzyme activities. Using two different nitroxide derivatives of stearic acid, the order parameter and approximate rotational correlation times were calculated from ESR spectra of normal and fatty acid-modified plasma membranes. No significant differences was found in either parameter in these membranes. These results, in conjunction with earlier data from our laboratory and others, suggest that caution should be exercised in inferring changes in membrane 'fluidity' based on lipid modulation of biological membranes.

Adenylyl Cyclases↗
PubMed1984

Dimethylnitrosamine inhibits the glucagon-stimulated adenylate cyclase activity of rat liver plasma membranes and decreases plasma membrane fluidity.

The effect of the hepatocarcinogen dimethylnitrosamine on rat liver plasma membrane adenylate cyclase activity and lipid fluidity was assessed. Glucagon-stimulated adenylate cyclase activity exhibited a complex response to increasing concentrations of dimethylnitrosamine, whereas fluoride-stimulated adenylate cyclase activity was progressively inhibited. Maximal inhibitory effects were observed at a concentration of 15 mM in both cases. The activity of detergent-solubilized adenylate cyclase was unaffected by dimethylnitrosamine. ESR analysis using a fatty acid spin probe showed that dimethylnitrosamine produced a marked, dose-dependent reduction in the fluidity of the plasma membrane with a maximal effect occurring at 20 mM. Dimethylnitrosamine also elevated the temperature at which the lipid phase separation occurred in rat liver plasma membranes, from 28 degrees C to 31 degrees C. The non-carcinogenic but structurally similar compound, dimethylamine hydrochloride neither inhibited adenylate cyclase nor decreased plasma membrane fluidity. It is suggested that the decrease in membrane fluidity, induced by dimethylnitrosamine, via its effects on membrane fluidity, could influence plasma membrane function and cellular regulation.

Adenylyl Cyclases↗
PubMed1986

Characterization of a monoclonal antibody that binds equally to all apolipoprotein and lipoprotein forms of human plasma apolipoprotein B. II. Isolation of apolipoprotein B-containing lipoproteins from human plasma.

Monoclonal antibody ('Pan B' antibody) that binds equally to all major forms of human plasma apolipoprotein B was used in an immunoaffinity chromatography procedure to isolate apolipoprotein B-containing lipoproteins from hyperlipidemic human plasma. These lipoproteins were compared with lipoproteins in native plasma, with lipoproteins isolated by polyclonal antibodies and with lipoproteins isolated by the conventional ultracentrifugational method. Judged by the apolipoprotein and lipid composition, lipoproteins isolated with 'Pan B' antibody were virtually identical to those isolated by ultracentrifugation or polyclonal antibodies. Lipoproteins isolated by 'Pan B' antibody were comparable in size and shape to the lipoproteins in native plasma and to the lipoproteins isolated by polyclonal antibodies or ultracentrifugation. The immunoaffinity column with monoclonal 'Pan B' antibody retained all apolipoprotein B-containing lipoproteins and showed significantly higher capacity than polyclonal immunoaffinity column. The column with the highest capacity allowed the isolation from whole plasma of 0.144 mg of apolipoprotein B per ml of gel in less than 2 h.

Animals↗
PubMed1988

Gangliosides in the blood plasma: levels of ganglio-series gangliosides in the plasma after administration of brain gangliosides.

The temporal change in the levels of the gangliotetraose-series gangliosides, i.e., GMla, GDla, GD1b, GT1b, in the blood plasma after intramuscular administration of bovine brain gangliosides (5 mg/kg) to beagle dogs (11.3-12.2 kg) was determined with high sensitivity by a recently developed thin-layer chromatography/enzyme-immunostaining method (Hirabayashi, Y., Koketsu, K., Higashi, H., Suzuki, Y., Matsumoto, M., Sugimoto, M. and Ogawa, T. (1986) Biochim. Biophys. Acta 876, 178-182). The amounts of GMla, GDla, GD1b, GT1b and their combined total in the plasma of beagle dogs before administration of gangliosides were 21 +/- 1, 36 +/- 7, 15 +/- 2, 16 +/- 2 and 88 +/- 6 pmol/ml of blood plasma, respectively. Trapezoidal calculation showed that the times of the maximum levels of GMla, GDla, GDlb, GTlb and the total of the their levels in the plasma were 8.0 +/- 1.2, 8.7 +/- 0.7, 6.3 +/- 2.0, 17.0 +/- 7.0 and 8.7 +/- 0.7 h after the administration of gangliosides, and their maximum concentrations were 517 +/- 37, 654 +/- 53, 160 +/- 5, 184 +/- 20 and 1383 +/- 74 pmol/ml, respectively. The maximum level of each ganglioside decreased gradually, reaching the normal level after 10 days. The half-maximum level of each ganglioside occurred 2-3 days after the administration. Asialo GM1 (GA1) was not detected plasma at any of the test times.

Animals↗