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Transfer of plasma lipoprotein components and of plasma proteins into aortas of cholesterol-fed rabbits. Molecular size as a determinant of plasma lipoprotein influx.

The arterial influx of esterified and free cholesterol from low density lipoproteins and very low density lipoproteins in 20 hypercholesterolemic rabbits was measured simultaneously by the use of lipoproteins labeled in vivo with [3H]- and [14C]-cholesterol. The simultaneous arterial influx of either [3H]-leucine-labeled very low density lipoproteins, low density lipoproteins, high density lipoproteins, or plasma proteins was also measured in each rabbit. The arterial influx was calculated as intimal clearance, i.e., the influx of a given fraction divided by its plasma concentration. The intimal clearance of low density lipoprotein esterified cholesterol was equal to that for the apolipoproteins of that fraction, which is compatible with an arterial influx of intact low density lipoprotein molecules. The intimal clearance of very low density apolipoprotein or cholesteryl ester was less than that for low density lipoprotein, whereas high density lipoprotein and albumin clearances exceeded low density lipoprotein clearance by 1.5- to 3-fold. The intimal clearances of plasma proteins, high density, low density, and very low density lipoproteins decreased linearly with the logarithm of the macromolecular diameter. This indicates that the arterial influx of three plasma lipoprotein fractions and of plasma proteins proceeds by similar mechanisms. Apparently the relative intimal clearances of lipoproteins are more dependent on their size relative to pores or vesicular diameters at the plasma-artery interface than on specific interactions between lipoproteins and the arterial intimal surface.

Animals↗

Determination of serotonin in whole blood, platelet-rich plasma, platelet-poor plasma and plasma ultrafiltrate.

The important biogenic amine, serotonin (5HT), was determined in whole blood, platelet-rich plasma (PRP), platelet-poor plasma (PPP), and plasma ultrafiltrate after simple deproteinization. Following ion-pair chromatography on standard or narrow-bore reverse-phase columns, 5HT and the internal standard (N-methylserotonin-NMS) were detected by fluorometry with absolute detection limits of 2-4 pg. Levels obtained for whole blood and PRP were in agreement with previous methods. However, mean (+/- SD) values obtained for platelet-poor plasma (PPP) of 578 +/- 277 pg/ml (N = 7) were approximately 3-fold lower than the lowest previous reports. We also report the first determination of 5HT in plasma ultrafiltrate, having observed mean levels of 387 +/- 222 pg/ml (N = 7).

Adult↗

Measurement of plasma renin concentration using exogenous human renin substrate in normal subjects: correlation with plasma renin concentration and plasma aldosterone concentration.

Measurement of plasma renin concentration (PRC) was done in normal subjects at rest and under acute stimulation of renin release under unrestricted sodium intake. Concurrent measurements of plasma renin activity (PRA) and plasma aldosterone concentration (PA) were carried out. The mean values of PRC at rest and after stimulation of renin release were 12.8 +/- 1.3 (SEM) and 21.7 +/- 4.4 (SEM) ng AT I/ml/h, respectively. These corresponded to renin contents of 3.4 +/- 0.34 (SEM) X 10(-5) Goldblatt units and 5.8 +/- 0.36 (SEM) respectively. The mean percent increase of PRC (82.1 +/- 19.3 (SEM)) %) was almost indentical to that of PA (81.5 +/- 16.4 (SEM) %), but differed from that of PRA (269 +/- 83.1 (SEM) %). A very high correlation between concurrent PRC and PA (r = 0.92, P less than 0.001) was found in normal subjects at rest and under acute stimulation of renin release. A good correlation between PRC and PRA (r = 0.85, P less than 0.001) was also observed. However, a higher correlation between percent increases of PRC and PA (r = 0.92, P less than 0.001) than that of PRA and PA (r = 0.80, 0.01 less than P less than 0.005) was found. Results show that PRA is a good index of the renin content in plasma in normal subjects at rest and PRC reflects actual renin concentration in plasma at rest as well as under stimulation of renin release.

Adult↗

Plasma substitution with 3% dextran-60 in orthopaedic surgery: influence on plasma colloid osmotic pressure, coagulation parameters, immunoglobulins and other plasma constituents.

To study the effects on plasma proteins, blood coagulation and fibrinolysis of dextran-60, given as plasma volume substitute in a 3% solution, 57 patients were studied preoperatively and for 8 days postoperatively in conjunction with elective orthopaedic surgery. Three groups were formed according to the blood loss during the day of surgery: Group I (n = 22) less than 30%, Group II (n = 24) 30-50% and Group III (n = 11) greater than 50% of the estimated blood volume. Dilution to a haemoglobin concentration of 110 g.1-1 was intended and erythrocytes transfused accordingly. No platelets were transfused. All patients received similar amounts of crystalloids. Nine patients in Group III received plasma and/or albumin solution for further volume replacement once the maximum dose of dextran (1.5 g.kg-1) was reached. Dextran-70 was given on days 1 and 3 postoperatively for thromboprophylaxis. No patient exhibited clinical signs of thrombosis or embolism. Mean postoperative bleeding times were longer than preoperatively, but still within the normal range in all groups. They were both pre- and postoperatively slightly longer in Group III, compared to the other groups, perhaps due to mild haemostatic disorders and/or undisclosed antiphlogistic therapy. Postoperative colloid osmotic pressures decreased by 11-19% in the three groups. Dilution of plasma constituents was also seen in the postoperative fall of platelet counts and of albumin, antithrombin and Factor X levels, most marked in Group III. Albumin levels on day 8 were still only 77-83% of preoperative values. IgG and IgM were decreased and the IgG level was still only 75% of preoperative on day 8.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Validation of an inductively coupled plasma-mass spectrometry method to quantify tungsten in human plasma. Determination of percentage binding to plasma proteins.

BACKGROUND: The aim of this paper was to validate an inductively coupled plasma-mass spectrometry (ICP-MS) method to quantify tungsten in human plasma and to study its percentage binding to plasma proteins. METHODS: This method was validated with respect to accuracy, precision, selectivity and limits of quantification and of detection according to Good Laboratory Practice Guidelines. Calibration curves were obtained in the range 10-500 ng/ml. The extent of plasma protein binding was determined by ultrafiltration in the range 40-2000 ng/ml. RESULTS: A significant matrix effect was observed. The linearity of this method was statistically proven. Precision ranged from 0.76% to 6.49%, and accuracy from 97% to 102%. The lower limit of quantification (LLOQ) was 10 ng/ml. The mean percentage of unbound fraction was 89%. CONCLUSIONS: The results obtained indicate that the method described fulfills the accuracy and precision requirements necessary to carry out pharmacokinetic studies in man.

Blood Proteins↗

Plasma plasminogen activator inhibitor-I is associated with plasma leptin irrespective of body mass index, body fat mass, and plasma insulin and metabolic parameters in premenopausal women.

Leptin, the satiety hormone expressed almost exclusively in adipose tissue, is a marker of body fat accumulation in humans. Recent studies have shown that plasminogen activator inhibitor-1 (PAI-1), a prothrombotic factor associated with atherosclerosis complications, is also produced in adipose tissue. The objective of the present study was to determine whether PAI-1 antigen plasma concentrations are associated with leptin plasma levels or the body fat mass (FM) independently of the variables known to influence PAI-1 production. Sixty-one nondiabetic women aged 18 to 45 years with a wide range of values for the body mass index ([BMI] 18.1 to 37.7 kg/m2) were evaluated for (1) body FM and fasting plasma levels of (2) PAI-1 antigen, (3) PAI-1 activity, (4) leptin, (5) insulin, (6) blood glucose, and (7) lipids (cholesterol, high-density lipoprotein [HDL]-cholesterol, and triglycerides [TG]). Body FM and fat-free mass (FFM) were estimated during fasting conditions by the bioimpedance analysis (BIA) method using a tetrapolar device. Body fat distribution was evaluated by the waist circumference and the waist to hip ratio (WHR). FM was directly associated with both PAI-1 antigen (r = .585, P < .001) and PAI-1 activity (r = .339, P < .001). Seemingly, leptin was positively related to both PAI-1 antigen (r = .630, P < .001) and PAI-1 activity (r = .497, P < .001). Moreover, both PAI-I antigen and PAI-1 activity were directly correlated with FFM (r = .285, P < .05, and r = .336, P < .01, respectively), BMI (r = .594, P < .001, and r = .458, P < .001, respectively), and WHR (r = .510, P < .001, and r = .391, P < .005, respectively). Insulin was directly related to PAI-1 antigen (r = .540, P < .001), PAI-1 activity (r = .259, P < .05), leptin (r = .447, P < .001), and FM (r = .435, P < .001). The association between PAI-1 antigen (dependent variable) and leptin or FM was tested by a stepwise regression model simultaneously including leptin, FM, BMI, WHR, age, FFM, and fasting insulin, blood glucose, TG, cholesterol, and HDL-cholesterol as independent variables. PAI-1 antigen maintained a significant positive independent relationship only with leptin (t = 2.923, P < .01), insulin (t = 3.489, P < .001), and fasting blood glucose (t = 2.092, P < .05), and a negative independent relationship with HDL-cholesterol (t = -2.634, P < .05). In conclusion, the strong relationship between PAI-1 antigen and leptin irrespective of other variables known to influence these factors seems to indicate that leptin per se may potentially increase PAI-1 plasma concentrations in obese subjects.

Adipose Tissue↗

Diurnal variations of plasma aldosterone in supine man: relationship to plasma renin activity and plasma cortisol.

In order to investigate the role of renin secretion and of ACTH on the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), plasma cortisol (PC) and PA were determined at short-time intervals in 10 normal supine men. Six subjects were studied under a normal sodium intake and 4 under sodium restriction. In 4 subjects the secretion of ACTH was suppressed by dexamethasone. Under normal sodium intake changes in PA seemed to be more in parallel with changes in PC than by those in PRA as indicated by a higher significant correlation between PA and PC than between PA and PRA in 3 of the 4 subjects. In 1 subject no correlation was observed between PA and PC despite visual synchronism between the plasma concentrations of both hormones. Under dexamethasone medication fluctuations in PA were followed by those in PRA while PC was less than 2 mug/100 ml. In the sodium restricted state, changes in PA were closely paralleled and significantly correlated to PRA while no correlation was seen between PA and PC. Under dexamethasone medication the significant correlation between PA and PRA persisted. Our results indicate that in normal supine man the influence of ACTH and renin on PA may vary with different sodium intakes. Under normal sodium intake ACTH seems to be the dominant factor controlling PA, whereas under sodium restriction changes in PA are mediated through the renin angiotensin system. When the secretion of ACTH is suppressed by dexamethasone, renin controls PA both under normal and low sodium intake.

Adrenocorticotropic Hormone↗

[Measurement of relative plasma volume and plasma refilling rate during ultrafiltration of hemodialysis by measuring apparatus of plasma colloidal osmotic pressure].

BACKGROUND: The objective of this study is the prevention of unexpected hypotension during hemodialysis caused by unsuitable filtration rate. METHODS: The plasma colloidal osmotic pressure (COP) was measured continuously during ultra-filtration, and relative plasma volume (%PV) and plasma refilling rate (PRR) were calculated during 12 ECUMs and one dialysis on twelve patients in early stage of chronic renal failure. Values of %PV and PRR calculated from COP were drawn in graphic curves, and analysed to obtain characteristic pattern. Minimum value of %PV (%PV min), maximum value of PRR (PRRmax) and time for PRR to decrease to 95% (95% PVt) on the curves were documented simultaneously. RESULTS: At the initial stage of %PV curve, obvious fall was observed on 6 of 13 estimation (initial fall of %PV). On the contrary at the initial stage of PRR curve, obvious rise was observed on 5 estimation (initial rise of PRR). A close relationship was indicated between the two phenomenons. In 6 cases with initial fall of %PV and in 5 cases with initial rise of PRR body weight, PRRmax and 95%PVt were lower than another cases without it. The ultra-infiltration velocity was estimated to be relatively high in these groups. In these 8 cases, filtrated water volume was judged as adequate clinically. In 4 of 5 cases without final fall of PRR, it was judged as inadequate and needed to evacuate more 0.9 to 3.0 kg (average of 1.8 +/- 1.07) of water from the patients. CONCLUSIONS: From the above, we concluded that our method is useful for deciding suitable velocity of ultrafiltration and dry weight in hemodialysis therapy.)

Adult↗

Comparison of measurement of effective renal plasma flow by single plasma sample and plasma disappearance slope/volume methods.

Numerous simplified methods for the estimation of ERPF have described, including the so-called slope/intercept (SI) methods, based on the analysis of the slope of certain segments of the 131I-OIH plasma disappearance curve and its y-axis intercept, and the single sample (SS) clearance method, based on theoretical volumes of OIH distribution at some fixed time after injection. Using ERPFs estimated from compartment analysis of the entire 60-min plasma disappearance curve, we have compared the errors of data calculated from use of eight SI methods made at various times along the disappearance curve with that from the optimum SS curve. The errors obtained from the SS method were approximately 50% less than those obtained from the SI methods. The errors of the SI methods are greater at both ends of the 60-min plasma curve than when samples are drawn near the mid-time. The SS method appears to be the method of choice for the estimation of ERPF using single injection techniques.

Adolescent↗

Characterization of plasma lipoproteins in patients heterozygous for human plasma cholesteryl ester transfer protein (CETP) deficiency: plasma CETP regulates high-density lipoprotein concentration and composition.

To understand the role of human cholesteryl ester transfer protein (CETP) in plasma lipoprotein metabolism, CETP activity and mass levels, lipoprotein and apolipoprotein concentrations, and the size of high-density lipoprotein (HDL) were determined in 15 heterozygotes and compared with those of four homozygotes and 20 normolipidemic controls. Plasma CETP activity and mass were totally deficient in the four homozygotes for CETP deficiency, while heterozygotes had approximately half the level of normals. CETP activity positively correlated with CETP mass levels (r = .95, P less than .001). No significant difference was observed in the level of low-density lipoprotein (LDL)-cholesterol among the three groups. The concentration of HDL2-cholesterol in the heterozygotes was approximately twice as high as that in controls, while that of homozygotes was sixfold higher than that in controls. No significant difference in the HDL3-cholesterol level was observed among the three groups. The HDL2-cholesterol to HDL3-cholesterol ratio of homozygotes was sixfold higher than that of controls, while heterozygotes showed intermediate values between homozygotes and controls. Negative correlations were found between CETP activity and HDL2-cholesterol level (r = -.884, P less than .001) and between CETP mass and HDL2-cholesterol level (r = -.829, P less than .001). Plasma apolipoprotein (apo) A-I, C-III, and E were markedly increased in homozygotes, but the differences between normal and heterozygotes were not statistically significant. The HDL size of homozygotes, determined by high-performance liquid chromatography (HPLC), was large, whereas that of heterozygotes was intermediate between homozygotes and normals.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗

Acute changes in plasma renin activity, plasma aldosterone concentration and plasma electrolyte concentrations following furosemide administration in patients with congestive heart failure--interrelationships and diuretic response.

We studied the effects of furosemide on plasma renin and plasma aldosterone in 8 patients with mild to moderate congestive heart failure. In particular, we tried to correlate these effects with changes in plasma electrolyte concentrations and with the diuretic response on furosemide. We concluded that the diuretic response in patients with congestive heart failure is not dependent on the initial serum renin nor on the initial serum aldosterone concentration. The diuretic response did not correlate either with the changes in serum renin and/or serum aldosterone concentration. Serum renin and serum aldosterone correlated mutually before and after intravenous furosemide. We confirmed the inverse correlation between serum sodium and serum renin. SeNa and SeK correlated at all times with serum aldosterone; SeCl correlated with serum aldosterone only before intravenous furosemide administration. Indirect evidence could be provided that in patients with congestive heart failure a decreased renal blood flow is present, using the urinary beta 2-microglobulin concentration. Aldosterone has again, indirectly, proved to be integrated in the renal magnesium handling.

Aged↗

The influence of plasma renin substrate on the relationship between plasma renin activity and plasma renin concentration. An experimental study in hyper- and hypothyroid rats.

The effects of endogenous Plasma Renin Substrate (PRS) on the relationship between Plasma Renin Activity (PRA) and the Plasma Renin Concentration (PRC) have been studied in hyperthyroid rats, by I-triiodothyronine (T3) administration and in hypothyroid rats, by propylthiouracil (PTU) treatment, to clarify if PRA changes are an adequate index for evaluating the renin-angiotensin changes during the alterations in the thyroid function. Although in experimental situations studied the induced variation on PRC explains a 62 per cent of the changes in PRA, finding a good lineal correlation between both parameters (r = 0.79, P less than 0.001). Not only does PRS play an important role on the kinetic of the enzymatic reaction but also explains jointly with PRC up to a 85 per cent of PRA alterations. PRS changes become more important during thyrotoxicosis where they limit in a higher degree the velocity of reaction due to inverse relationship between PRC and PRS (r = 0.74, P less than 0.001).

Angiotensinogen↗

The diurnal rhythm of plasma aldosterone, plasma renin activity, plasma cortisol and serum growth hormone and subnormal responsiveness of aldosterone to angiotensin-II in the patients with normotensive acromegaly.

The diurnal rhythm of plasma aldosterone concentration (PA), plasma renin activity (PRA), plasma cortisol (PC) and serum growth hormone (GH) were examined in 5 cases of normotensive acromegaly and the results were compared with the observations in normal subjects. Moreover, the response of PA to angiotensin-II infusion was studied in 6 cases of normotensive acromegaly. A normal diurnal rhythm with the lowest values in the evening or midnight and the highest values in the morning was observed in 3 of 5 cases in PA and 3 of 4 cases in PC. On the other hand, no apparent rhythm of GH was observed in any cases and that of PRA in 4 of 5 cases. Although there was a significant positive correlation between PA and PC, no significant correlation was demonstrated between PA and PRA. The response of PA to angiotensin-II fusion was significantly suppressed in normotensive acromegaly as compared to the normal subjects in spite of normal levels of PRA except for 1 case. The above observations were interpreted to suggest that the aldosterone regulation system is slightly altered in a certain number of patients with normotensive acromegaly in contrast to the normal subjects in which PRA is the main contributing factor. The low PA and suppressed response of PA toangiotensin-II infusion may suggest the defective action of angiotensin-II infusion on the adrenal gland.

Acromegaly↗

[Comparison of single plasma sample methods and prediction of dual plasma sample method in measurement of 99mTc-Diethylene Triamine Pentaacetic Acid plasma clearance].

OBJECTIVE: To find an applicable condition of the single-plasma-sample method (SPSM) to measure the glomerular filtration(GFR) with (99m)Tcj Diethylene Triamine Pentaacetic Acid ((99m)Tc-DTPA), and predict the value of (99m)Tc-DTPA plasma clearance by dual plasma sample method (DPSM ) from that by SPSM. METHODS: Three hundred and thirty five patients with chronic kidney disease (CKD) were selected (192 males and 143 females). The average age was 51.91+/-14.76 years. The GFR was determined simultaneously by 2 methods: (1) SPSM (sGFR); (2) DPSM (tGFR), using DPSM as reference standard, sGFR calculated from the different SPSM was compared with tGFR. An equation was developed to predict tGFR from sGFR. GFR estimated by abbreviated Modification of Diet in Renal Disease (MDRD) equation (aGFR) was evaluated as the criterion in selection of DPSM and SPSM. The condition that DPSM could be substituted by SPSM in GFR measurement was given. RESULTS: When tGFR >or= 30 mL/(minx1.73 m(2)), all of the sGFR were significantly correlated with tGFR. Among them, Watson modified Christensen and Groth's equation at sample time=240 min tended to be the most accurate (r=0.977, RMSE=10.91), and tGFR could be predicted from sGFR using the equation: Predicted tGFR [mL/(minx1.73 m(2))]=7.755 4+0.789 3xsGFR+0.002 4 xsGFR2 (n=297, r2=0.959 1, P<0.001). When aGFR was less than 50 mL/(minx1.73 m(2)), the diagnostic sensitivity of tGFR<30 mL/(minx1.73 m(2)) was 94.7%, and recommended as the criterion in selection of DPSM and SPSM. CONCLUSION: When aGFR >or=50 mL/(minx1.73 m(2)), DPSM can be substituted by SPSM in GFR measurement.

Algorithms↗

Fresh frozen plasma: plasma secured and virus inactivated plasma.

Two procedures are now used in France to reduce the risk of viral transmission by blood plasma transfusion: either a quarantine method or a chemical method based on solvent-detergent technic. Since August 4th, 1992, a chemical virus inactivated blood plasma product from the Bordeaux blood bank has been authorized.

Blood Component Transfusion↗

Circadian rhythms of plasma atriopeptin, plasma renin activity and plasma aldosterone in patients with hepatorenal syndrome.

The etiology of hepatorenal syndrome (HRS) is still incompletely understood, but the atriopeptin-renin-aldosterone system plays an important role in its pathogenesis. Since this system presents a circadian rhythmicity, the aim of the study was to investigate the circadian rhythm in the circulating concentrations of atriopeptin (atrial natriuretic peptide, pANP), plasma renin activity (PRA) and plasma aldosterone (pA) in patients with HRS, compared with healthy controls. Venous blood samples were drawn during the span of a whole day and every two hours from a peripheral vein in 10 healthy subjects and in 10 patients with HRS. The circulating concentrations of pANP, PRA and pA were determined by radioimmunoassay. Statistical analysis was carried out by the "cosinor" method. The controls presented a significant (p < 0.05) circadian rhythm for each variable, whereas no rhythm (p > 0.05) was found in HRS patients. The pANP, PRA and pA rhythms were significantly (p < 0.05) different between the two groups, HRS patients having higher mean daily concentrations and larger circadian variations of pANP, PRA and pA than controls. Significant relations (p < 0.05) were demonstrated between the mean daily concentrations of pANP and PRA (r = 0.79), PRA and pA (r = 0.73) and PRA and pA (r = 0.76) in the controls; on the contrary, the HRS patients showed only a significant (p < 0.05) positive relation between pANP and PRA (r = 0.71). These results confirm the previous observation that the atriopeptin-renin- aldosterone system presents a well-defined circadian time structure in healthy subjects, while the HRS patients present a complete loss of the secretory sequentiality and of the circadian rhythm, with desynchronization of the whole system. This great upset in the temporal and functional organizations of the system could play an important role in promoting and/or in maintaining the hydro-electrolyte unbalance of HRS.

Aldosterone↗