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PubMed1994

Inhibitors of angiotensin converting enzyme decrease early atherosclerosis in hyperlipidemic hamsters. Fosinopril reduces plasma cholesterol and captopril inhibits macrophage-foam cell accumulation independently of blood pressure and plasma lipids.

The effect of two angiotensin converting enzyme (ACE) inhibitors on the development of atherosclerosis was determined in hyperlipidemic hamsters. Preliminary studies indicated that only fosinopril (50 mg/kg) temporarily decreased mean arterial pressure, while after chronic dosing fosinopril and captopril (50 mg/kg) were ineffective. The same dose of fosinopril and captopril inhibited the angiotensin I pressor response, indicating these agents suppressed ACE activity in vivo. In the 3 week atherosclerosis experiment, all hamsters were fed chow supplemented with 0.05% cholesterol and 10% coconut oil. Control hamsters were compared with those receiving either 50 mg/kg per day of fosinopril or 50 mg/kg per day of captopril. After 3 weeks, fosinopril reduced plasma total cholesterol, low density lipoprotein (LDL) plus very low density lipoprotein cholesterol and total triglycerides by 17%, 27% and 45%, respectively. Captopril only reduced high density lipoprotein cholesterol by 20%. Neither fosinopril or captopril altered blood pressure at 3 weeks. Atherosclerosis was quantified from en face preparations of the lesion-prone aortic arch that were stained with oil red O (for cholesteryl ester and triglycerides). In control hamsters, oil red O labeled numerous subendothelial macrophage-foam cells located along the inner curvature of the aortic arch. Compared with controls, fosinopril reduced the number of intimal macrophage-foam cells/mm2, foam cell size and the fatty streak area by 85%, 38% and 90%, respectively. Captopril decreased these parameters by 44%, 16% and 53%. Thus captopril decreased early atherosclerosis without affecting plasma LDL cholesterol or blood pressure, which suggested that inhibiting ACE (or kininase II) directly impeded the accumulation and formation of macrophage-foam cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

High-performance liquid chromatographic determination of plasma triglyceride type composition in a normal population of Barcelona. Relationship with age, sex and other plasma lipid parameters.

A coupled TLC-HPLC procedure is proposed for the separation and determination of plasma triglycerides. The method was tested by application to plasma samples corresponding to a normal population of Barcelona (Spain). Eighteen different triglyceride types were identified and their relative proportions were established, in order to give a "normal profile" for men and women. Sex-related differences (p < 0.05) were only found for dioleostearin and palmitodilinolein + linoleooleopalmitolein (LLP+LOPa). A correlation study showed that palmitodiolein and total cholesterol levels increase with age, whereas LLP-LOPa decreases in men and palmitolinoleoolein + palmitooleopalmitolein in women.

Adolescent↗

PubMed1994

Practical applications of element-specific detection by inductively coupled plasma atomic emission spectroscopy and inductively coupled plasma mass spectrometry to ion chromatography of foods.

Three practical examples are presented to demonstrate the utility of element-selective detection for ion chromatography (IC). The determination of As species in a liquid health food supplement by IC with inductively coupled plasma atomic emission spectroscopy (IC-ICP-AES) is shown to confirm results obtained for total As. IC-ICP-AES is also used to investigate the identity of an unknown peak in a sample of shrimp commercially treated with tripolyphosphate. Finally, results are presented for the determination of residual bromate in baked goods by IC with inductively coupled plasma mass spectrometry detection.

Animals↗

PubMed1995

Chromium speciation by anion-exchange high-performance liquid chromatography with both inductively coupled plasma atomic emission spectroscopic and inductively coupled plasma mass spectrometric detection.

Development of a new method for the determination of Cr(III) and Cr(VI) is described. Anion-exchange high-performance liquid chromatography (HPLC) was used to separate Cr(III) and Cr(VI) with on-line detection by inductively coupled plasma atomic emission spectroscopy (ICP-AES) at 2766 A in preliminary studies, and inductively coupled plasma mass spectrometry (ICP-MS) with single-ion monitoring at m/z 52 and m/z 53 for final work. A mobile phase consisting of ammonium sulfate and ammonium hydroxide was used, and a simple chelation procedure with EDTA was followed to stabilize the Cr(III) species in standard solutions. ICP-MS results indicated the feasibility of using chromium isotope m/z 53 instead of the more abundant m/z 52 isotope due to a high mobile-phase background most significantly from the SO+ polyatomic interference. The absolute detection limits based on peak-height calculations were 40 pg for Cr(III) and 100 pg for Cr(VI) in aqueous media by HPLC-ICP-MS. The linear dynamic range extended from 5 ppb (ng/ml) to 1 ppm (micrograms/ml) for both species. By HPLC-ICP-AES, detection limits were 100 ng for Cr(III) and 200 ng for Cr(VI). Cr(III) was detected in NIST-SRM 1643c (National Institute of Standards and Technology-Standard Reference Material, Trace Elements in Water) by HPLC-ICP-MS at the 20 ppb level.

Chromatography, High Pressure Liquid↗

PubMed1988

Diminished glucocorticoid tonus in obese strain (OS) chickens with spontaneous autoimmune thyroiditis: increased plasma levels of a physicochemically unaltered corticosteroid-binding globulin but normal total corticosterone plasma concentration and normal glucocorticoid receptor contents in lymphoid tissues.

Obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis (SAT) display several signs of a general immune dysbalance, some of which may be related to altered endocrine mechanisms such as the glucocorticoid tonus. The latter is the combined result of corticosterone (CN) production, metabolism as well as excretion, and the binding of CN to corticosteroid binding globulin (CBG) and glucocorticoid receptors (GR). The present study deals with the comparative investigation of these parameters in OS and normal White Leghorn (NWL) chickens. The results obtained with radioimmunoassay for CN and radioligand saturation assays for plasma CBG as well as GR in the thymus were as follows: (1) both OS and NWL have equal total CN levels; (2) however, OS chickens exhibit elevated CBG levels, whereas the physicochemical parameters (equilibrium affinity, specificity spectrum) of CBG were equal in OS and NWL; (3) the GR capacities and affinities were equal in both OS and NWL throughout development until thymic involution. Similarly, the specificity, affinity, and sedimentation behaviour were equal in OS and NWL. (4) Furthermore, no differences were found in the response of OS and NWL splenocytes to the suppressive effect of glucocorticoids in vitro, also excluding postreceptor alterations at the cellular level in the OS. From these findings we conclude that the increased CBG levels, which are not compensated for by either increased CN plasma levels or by increased receptor capacities or affinities in lymphatic organs, represent a diminished glucocorticoid tonus in OS chickens. This may have immunoregulatory consequences which, in turn, may contribute to the development of SAT.

Animals↗

PubMed1975

The effect of somatostatin on plasma noradrenaline and plasma adrenaline concentrations during exercise and hypoglycemia.

The effect of somatostatin, on the secretion of noradrenaline and adrenaline was studied in eight normal subjects during exercise and in insulin induced hypoglycemia. Plasma growth hormone response to exercise and hypoglycemia was almost totally suppressed by somatostatin. Plasma noradrenaline during exercise tended to be lower during the infusion of somatostatin but the difference was not significant. During the infusion of somatostatin the secretion of adrenaline was increased. This was seen during exercise but was much more pronounced during hypoglycemia. The blood glucose concentration attained after insulin injection was lower during the infusion of somatostatin and evidence is presented which indicates that the higher adrenaline values during hypoglycemia were due to the lower blood glucose values attained. In conclusion the secretion of catecholamines are not inhibited by a dose of somatostatin which nearly totally suppresses the secretion of growth hormone.

Adult↗

PubMed1993

The role of fatty acid saturation on plasma lipids, lipoproteins, and apolipoproteins: I. Effects of whole food diets high in cocoa butter, olive oil, soybean oil, dairy butter, and milk chocolate on the plasma lipids of young men.

The present studies were conducted to evaluate the cholesterolemic effects of whole-food diets high in stearic acid. In study no. 1, normocholesterolemic young men were fed diets high in stearic acid provided by cocoa butter (CB); oleic acid provided by olive oil (OO); linoleic acid provided by soybean oil (SO); and myristic acid (and lauric acid) provided by dairy butter (B). In study no. 2, different subjects with similar baseline characteristics were fed diets high in stearic acid provided by milk chocolate (C), CB, CB+B (4:1, MIX), and myristic (and lauric) acid provided by B. Both studies used a randomized, crossover, double-blind experimental design, and experimental subjects (n = 18 for study no. 1 and n = 15 for study no. 2) in each study consumed every diet for 26 days with a 1-month wash-out period between each experimental period. The diets provided 37% of calories from fat, of which 81% was provided by the test fat. Ten ounces (280 g) C was provided daily by the C diet. In study no. 1, the B diet was hypercholesterolemic, whereas the SO diet was hypocholesterolemic, compared with the other diets. The OO and SO diets were hypocholesterolemic compared with the CB diet. Low-density lipoprotein (LDL) cholesterol levels, in general, paralleled the changes in plasma total cholesterol levels. SO significantly decreased apolipoprotein (apo) B levels compared with the other diets. Plasma very-low density lipoprotein (VLDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apo A-I levels were unaffected by the experimental diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

A new method for measurements of plasma protein steroid-binding kinetics in human plasma at 37 C.

The equilibrium kinetics in vivo of free and protein-bound steroid hormone were examined at 37 C. Human plasma was pumped through a 1 m PVC catheter and tritiated steroid hormone continuously added at the inlet. The plasma was collected and rerun through a new catheter 24 h later. A significantly (P less than 0.05) higher uptake of steroid hormone was observed in the first parts of the catheter during the first passage when compared to the second passage. The results indicate that non-equilibrium conditions existed for testosterone (greater than 10 sec), estradiol (4 sec), estrone (greater than 2 sec), and estriol (greater than 2 sec) while no delay was observed for progesterone. The results indicate that the counter-current transfer between the testicular and ovarian vessels, respectively, may create a physiologically important, temporarily increased concentration of available hormones in the arterial blood supply to the organs.

Blood Proteins↗

PubMed1978

Undifferentiated and differentiated L6 myoblast plasma membranes. I: Comparison of the morphology of plasma membrane vesiculation and the factors influencing the vesiculation process.

Monolayer cultures of a variety of cell lines can be induced to shed plasma membrane vesicles by exposure to 25 mM formaldehyde--2 mM dithiothreitol. An analysis of the process of membrane shedding can provide a method to probe the general characteristics of the plasma membrane in different cell populations. We have, therefore, analyzed membrane shedding in L6 myoblasts at different stages of differentiation. The results show that the morphology of membrane shedding is comparable in undifferentiated or differentiated L6 myoblasts, as are the factors that influence the process of membrane shedding. L6 myoblasts at various stages of differentiation have similar requirements for metabolic energy, physiological temperature, pH, and monovalent and divalent cations.

Cell Differentiation↗

PubMed1989

Influence of plasma protease activation on electroimmunoassay and nephelometry of plasma fibronectin in sepsis.

In vitro experiments have shown that proteases such as trypsin, kallikrein and plasmin may split plasma fibronectin, yielding changes in apparent mass concentration, i.e.: a decrease when using immunonephelometry (IN), and an increase when using electroimmunoassay (EIA). In the present in vivo study, plasma from 49 patients with severe infections was assayed for fibronectin by IN and EIA, and for prekallikrein, plasminogen and antithrombin. In patients with normal prekallikrein (n = 26) and plasminogen (n = 23), the agreement between the two fibronectin assay methods was good (ratio EIA/IN = 0.99 +/- 0.06); a similar good agreement was found in 45 healthy blood donors (ratio 0.97 +/- 0.02). In contrast, the 20 patients with low prekallikrein showed fibronectin values that were significantly higher by EIA than by nephelometry (ratio 1.27 +/- 0.10, p less than 0.01). Similarly, the 26 patients with low plasminogen had a significantly increased ratio (1.21 +/- 0.09, p less than 0.05). No such difference was seen, however, between patients with low or normal antithrombin. Thus, kallikrein and plasmin activation in vivo appear to increase the fibronectin concentration measured by EIA, possibly due to the formation of small fragments with increased electrophoretic motility.

Antithrombins↗

PubMed1977

Prostaglandins E and F in uterine venous plasma in relation to peripheral plasma levels of progesterone and 20alpha-hydroxyprogesterone in the rat throughout pregnancy and parturition.

Prostaglandins E and F in uterine venous plasma and progesterone (P) and 20alpha-hydroxyprogesterone (20alpha-OH-P) in peripheral plasma were measured by radioimmunoassays throughout pregnancy and parturition in the rat. E Prostaglandins are low (approx. 2 ng/ml) and maintain a more or less constant level throughout most of the pregnancy except just before parturition when they rise to 3.8 ng/ml on day 20. F Prostaglandin levels are always higher than E prostaglandins and show distinct peaks around day 5 (5 ng/ml), day 11 (7 ng/ml), and before parturition (8.4 ng/ml). Progesterone levels are higher than 20alpha-OH-P levels throughout most of the pregnancy (day 6-20); however, during early pregnancy (day 1-5) and before parturition more 20alpha-OH-P than P is present in peripheral blood. The possible role of uterine venous prostaglandin levels in altering the 20alpha-OH-P/P ratio during pregnancy and parturition is discussed.

Animals↗

PubMed1992

Plasma tryptophan levels and plasma tryptophan/neutral amino acids ratio in patients with mood disorder, patients with obsessive-compulsive disorder, and normal subjects.

Fasting plasma tryptophan (TRP) levels and ratios of total plasma tryptophan to the sum of five large neutral amino acids (LNAAs)--tyrosine, phenylalanine, leucine, isoleucine, and valine--that compete with tryptophan for passage across the blood-brain barrier were found to be significantly lower in a group of 28 patients with major depression compared with 29 normal subjects and 21 patients with obsessive-compulsive disorder (OCD). The OCD group was divided in two subgroups: patients with OCD alone and patients with a co-diagnosis of major depression. Since it has been considered that these biological parameters reflect brain tryptophan and serotonin levels, our results suggest their importance in relation to the presence or absence of depressive symptoms. The values of the other LNAAs and their sum did not differ significantly among the groups.

Adolescent↗

PubMed1990

Release of iron from diferric transferrin in the presence of rat liver plasma membranes: no evidence of a plasma membrane diferric transferrin reductase.

The transfer of iron from diferric transferrin to bathophenanthroline disulfonate was measured under varying conditions by spectrophotometry and EPR spectroscopy. Intact rat hepatocytes efficiently mediated the transfer of iron from human diferric transferrin to bathophenanthroline disulfonate. Isolated rat liver plasma membranes, in contrast, failed to facilitate the reaction at pH 7.4 in the presence of NADH, although the membranes were able to reduce ferricyanide and to oxidize NADH. Oxidation of NADH was stimulated by diferric transferrin. However, ferricyanide reductase and transferrin-stimulated NADH oxidase activities were apparently not linked to release of iron from transferrin. Our results, together with theoretical considerations, show that the ability (or inability) of intact cells or isolated plasma membranes to facilitate the transfer of iron from transferrin to strong diferric iron chelators does not allow interferences about the existence of an iron reduction step as part of the process of cellular uptake of iron from transferrin.

Apoproteins↗

PubMed1979

Heroin addiction: relationship between the plasma levels of testosterone, dihydrotestosterone, androstenedione, LH, FSH, and the plasma concentration of heroin.

Changes in sexual function and hormone levels are commonly found in subjects addicted to narcotics. In this study we examined 16 male and 3 female addicts who had been taking heroin (H) in the last year in doses higher than 150 mg/day. In these patients, who presented similar clinical problems, we assayed by RIA the plasma levels of heroin, testosterone, (T), dihydrotestosterone (DHT), androstenedione (A), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) for periods of 150 min, 6 h and 9 h. We found a significant reduction of T and DHT concomitant with higher plasma concentrations of heroin but no relevant changes of A, LH and FSH. T and DHT returned to the initial levels after the decrease of heroin concentration. The GnRH test effectd on a female subject allowed us to make the diagnosis of hypothalamic amenorrhea. In the same patient no circadian rhythms for T, DHT and A were detected.

Adolescent↗

PubMed1991

Plasma morphine and morphine-6-glucuronide during chronic morphine therapy for cancer pain: plasma profiles, steady-state concentrations and the consequences of renal failure.

Morphine-6-glucuronide (M-6-G) is an active metabolite of morphine that may contribute to drug effects. To understand better the relationship between morphine and M-6-G in cancer patients receiving chronic therapy, we employed high performance liquid chromatography with electrochemical detection to measure: (1) morphine and M-6-G plasma concentrations following discontinuation of dosing in 2 patients, one receiving oral therapy and the other an intravenous infusion; (2) morphine and M-6-G concentrations in random blood samples taken at apparent steady state from 8 patients, 7 with normal renal function and 1 with mild renal insufficiency, who were receiving continuous morphine infusions; and (3) morphine and M-6-G concentrations in random blood samples taken over a period of weeks from 4 patients, 2 with stable and 2 with declining renal function. Results demonstrated a slightly slower decline in plasma M-6-G than morphine concentrations following drug discontinuation, as would be expected for metabolite and parent relationship; roughly similar M-6-G: morphine ratios (mean molar ratio = 1.22) across a broad range of morphine doses in patients with normal renal function; and an increase in this ratio over time in patients with progressive renal dysfunction. These data illustrate the kinetics of M-6-G in cancer patients receiving chronic morphine therapy and confirm the importance of renal function in determining the concentration of the metabolite.

Adult↗

PubMed1983

Effects of fasting on plasma lipids and cholesterol esterification in plasma, liver and intestinal mucosa in the char (Salmo alpinus L.).

1. CoA-dependent cholesterol esterification, measured as esterification of 3H-cholesterol, was demonstrated in homogenates of liver and intestinal mucosa of the char (Salmo alpinus L.). 2. Plasma concentration of triacylglycerols, unesterified and total cholesterol were significantly reduced to 43, 58 and 72% of the control values, respectively, after 6 weeks fasting. 3. The rate of cholesterol esterification in plasma and liver homogenate was significantly lower in the fasted fish compared to the controls, but the esterification activity in the homogenate of intestinal mucosa increased twofold in the fish fasted for 6 weeks.

Animals↗

PubMed1991

Comparative study on the determination of the anti-neoplastic drug teniposide in plasma using micellar liquid chromatography and surfactant-mediated plasma clean-up.

The potential of micellar liquid chromatography and of an on-line surfactant-mediated sample cleanup, which involves column-switching prior to conventional reversed-phase high-performance liquid chromatography, has been evaluated for the determination of the anti-neoplastic drug teniposide in plasma by using electrochemical detection. A major advantage of surfactant-mediated techniques is that they allow fully automated processing of plasma samples, because protein precipitation is prevented by the addition of the surfactant sodium dodecylsulphate. With the automated column-switching technique, a degree of sample enrichment and of selectivity can be attained, which is similar to that for the conventional procedure which, however, involves a labour-intensive off-line isolation of teniposide, using liquid-liquid extraction prior to chromatography. An inherent drawback of automated micellar liquid chromatography is that no sample clean-up or preconcentration can be carried out, which results in only a moderate detection limit and selectivity. The linearity, reproducibility and recovery of the surfactant-mediated techniques are similar to those of the conventional procedure. Based on the presented results, it was concluded that the surfactant-mediated column-switching technique is a highly attractive sample enrichment technique with respect to simplicity, speed and cost.

Chromatography, High Pressure Liquid↗

PubMed1993

Assay of human plasma cortisone by liquid chromatography: normal plasma concentrations (between 8 and 10 a.m.) of cortisone and corticosterone.

A high-performance liquid chromatographic method using ultraviolet detection to quantitate human plasma concentrations of cortisone simultaneously with cortisol and corticosterone is described. The method is based on the use of an octadecyl silica column (100 mm x 2 mm I.D., 3 microns), an ultraviolet absorbance detector (242 nm) with a 10 mm path length flow-cell, and a mobile phase composed of water-tetrahydrofuran-acetonitrile (82:10:8, v/v) containing 5 ml/l triethylamine and citric acid to adjust the pH of the buffer to 6.5. Flumethasone is used as the internal standard. The detection limit of the method for the three steroids is 300 ng/l using a 1-ml sample. The average inter-assay coefficient of variation for cortisone is 3.3% and the average recovery is 100.8%. Possible interferences from common drugs and endogenous and exogenous steroids in the method have been studied. Plasma concentrations (drawn from 8 to 10 a.m.) of cortisone and corticosterone for 43 normal volunteers have been determined.

Chromatography, High Pressure Liquid↗