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The relationship of plasma levels of pindolol in hypertensive patients to effects on blood pressure, plasma renin and plasma noradrenaline levels.

1. Fifteen, previously untreated, hypertensive patients were given 20 mg of pindolol, orally. The systolic and diastolic blood pressures fell significantly in 1 h; the effect was maximal 4 h after pindolol, and persisted for at least 8 h. 2. After oral administration of 20 mg of pindolol, its concentration in the plasma reached a peak in 2-3 h. At the end of 8 h, pindolol was not detectable in the plasma. 3. There was a significant relationship between the peak concentration of pindolol in plasma and the maximal change in blood pressure in fifteen previously untreated hypertensive patients. In a separate study of nine-nine hypertensive outpatients taking 15-80 mg of pindolol daily, the blood pressure responses corresponded generally to the concentration of pindolol in plasma 2-3 h after the morning dose. 4. There were no significant changes in plasma renin activity, plasma renin concentration or plasma noradrenaline concentration in the previously untreated patients taking 20 mg of pindolol. There was no relationship between initial plasma renin or noradrenaline levels and blood pressure responses to pindolol. Nor was there any significant relationship between the changes in plasma renin or noradrenaline levels and the changes in blood pressure.

Blood Pressure↗

Plasma arginine esterase in cystic fibrosis: kinetics of activation, identification as plasma kallikrein, reaction with alpha 2-macroglobulin and comparison with levels in normal plasma.

Treatment of normal plasma with chloroform and ellagic acid yielded esterase activity against tosylarginine methyl ester, which reached a maximum within 2 h. After 2 h most or all of the activity as resistant to inhibition by soybean trypsin inhibitor (STI), but was still sensitive to the low molecular weight inhibitors di-isopropyl fluorophosphate, aprotinin and prolyl-phenylalanyl-arginyl chloromethane. The activity ran in gel chromatography with alpha 2 macroglobulin (ampha 2M), as if it were due to an alpha 2M proteinase complex. The generation of the arginine esterase activity by chloroform and ellagic acid was apparently dependent on the activation of factor XII, being blocked by Polybrene. In plasma pretreated with methylamine-HCl (an inactivator of alpha 2M), the arginine esterase was 95% sensitive to inhibition by STI. With regard to substrate specificity, inhibition characteristics, and gel chromatographic behaviour, it was indistinguishable from plasma kallikrein (EC 3.4.21.34, formerly 3.4.21.8). The chloroform and ellagic acid treatment of plasma resulted in a disappearance of prokallikrein simultaneous with the appearance of the arginine esterase. By these criteria, the arginine esterase activity was attributable entirely to plasma kallikrein either in its free form (methylamine-treated plasma) or bound to alpha 2M (buffer-treated plasma). Comparisons of STI-sensitive and STI-resistant arginine esterase activities of plasma samples from cystic fibrosis patients, obligate heterozyotes or other groups showed no significant differences in levels of activity, kinetics of activation or gel chromatographic behaviour. We conclude that cystic fibrosis is unrelated to any abnormality in plasma arginine esterase activity, contrary to some previous reports.

Carboxylic Ester Hydrolases↗

Radioimmunoassay of plasma cholecystokinin (CCK), duodenal release of CCK, diurnal variation of plasma CCK, and immunoreactive plasma CCK components in man.

A precise and specific radioimmunoassay method for measuring plasma cholecystokinin (CCK) is described. The present assay system using a stable tracer iodinated by means of a modified Chloramine-T method followed by purification on a Sephadex G-15 and a SP Sephadex C-25 column, as well as careful corrections for non-specific plasma effects, allows measurements of fasting plasma CCK in the low pmol/l range; the significant rise in plasma CCK following duodenal infusion of fat; and the significant diurnal variation of plasma CCK. Apparent immunoreactive meal-stimulated plasma CCK was eluted from a Sephadex G-50 superfine column in four fractions. The first and largest peak probably represents plasma CCK bound to plasma proteins and non-specific plasma effects, the second and smaller peak big CCK with molecular weight between some 5,000 and some 30,000, the shoulders following the second peak ordinary CCK33 and CCK39 variant, and the final, and by far the smallest peak, may possibly represent COOH-terminal tetra- (CCK4) or octapeptides (CCK8) of CCK.

Animals↗

Methylene blue-photoinactivated plasma vs. fresh-frozen plasma as replacement fluid for plasma exchange in thrombotic thrombocytopenic purpura.

BACKGROUND AND OBJECTIVES: Plasma exchange with fresh-frozen plasma (FFP) is the treatment of choice in thrombotic thrombocytopenic purpura (TTP). Methylene blue-photoinactivated plasma (MBPIP) has been proposed as a safer alternative to FFP, but its effectiveness in the treatment of TTP is not well established. The purpose of this study was to investigate whether MBPIP is as effective as FFP in the treatment of TTP by plasma exchange. MATERIALS AND METHODS: A retrospective analysis was carried out of 56 TTP episodes, occurring between 1990 and 2003, which had been treated by plasma exchange. MBPIP was used for fluid replacement in 27 episodes and FFP in 29. The effect of plasma (MBPIP or FFP) on treatment outcomes was analysed by multivariate logistic regression. RESULTS: Compared to patients treated with FFP, those receiving MBPIP had an increased risk of dying from progressive TTP [adjusted odds ratio (OR) = 31; 95% confidence interval (CI): 1.2 to > 100], a greater number of recurrences while on plasma exchange therapy (OR = 4.6; 95% CI: 1.2-17), and a lower probability of attaining a sustained remission within 9 days of starting plasma exchange (OR = 5.2; 95% CI: 1.3-20). CONCLUSIONS: MBPIP seems to be less effective than FFP in the treatment of TTP. It is therefore prudent to avoid MBPIP until therapeutic equivalency to FFP has been established by randomized, controlled trials.

Adult↗

The rôle of plasma proteins in chronic expansion of plasma volume in tropical splenomegaly syndrome. III. The interrelationships of albumin, immunoglobulins and plasma volume.

The effect of alterations in serum protein levels on plasma volume in tropical splenomegaly syndrome has been investigated by determining plasma volume, serum albumin, globulin and immunoglobulin levels in 64 adult New Guineans suffering from this disease. Plasma volumes ranged from 51-2 to 129 ml./kg. Significant positive correlations were found between plasma volume and intravascular pools of albumin, IgG and IgM. Multiple regression analysis demonstrated that 70% of the variance in plasma volume in this series was attributable to increases in these three pools, IgM and IgG accounting for 42% of the total and albumin for 28%. It is probable that the unexplained 30% of plasma volume expansion arises through a splenic arterio-venous shunt effect. It is suggested that initially in tropical splenomegaly syndrome the splenic shunt and immunoglobulin overproduction combine to produce expansion of plasma volume and a fall in intravascular colloid osmotic pressure; that the latter provides the stimulus to increased albumin synthesis, and that this further aggravates the plasma volume expansion and the consequent dilutional anaemia commonly seen in this disease.

Blood Proteins↗

Renin binding proteins in plasma. Binding of renin to some of the plasma protease inhibitors, to lipoproteins, and to a non-trypsin-binding unidentified plasma protein.

Renin is found in mouse plasma as high molecular weight forms, in addition to the fully active 40 000 dalton form. By using freshly 125 I-labelled 40 000 dalton pure submaxillary mouse renin, no binding to plasma proteins was demonstrable. However, unfolding and refolding of the labelled renin by guanidine facilitated binding to specific mouse and human plasma proteins. By using antibodies against individual human plasma proteins, the specific binding proteins were identified to be the plasma protease inhibitors: alpha2-macroglobulin, inter-alpha-trypsin inhibitor, alpha2-antithrombin. Binding was also demonstrated to alpha1- and beta1-lipoproteins, albumin and to a non trypsin binding unidentified plasma protein. No binding to 56 other tested proteins was demonstrable. It is concluded that the native 40 000 renin does not bind, but that a conformational change of the renin molecule most likely is necessary before binding occurs. It is discussed whether or not inactive or high molecular weight forms of renin in plasma are 40 000 renin bound to plasma protease inhibitors and lipoprotein.

Animals↗

Quantitation of the novel anticonvulsant remacemide in rat and dog plasma and urine: application of the plasma methodology to measure the plasma protein binding of remacemide.

Sensitive and selective methods have been developed for quantitation of the novel anticonvulsant remacemide in rat and dog plasma and urine. The methods employed liquid-liquid extraction (urine) or ion-exchange solid-phase extraction (plasma), with an internal standard, followed by high-performance liquid chromatography with ultraviolet detection. The detection limit for both methods was 10 ng/ml. Overall accuracy was 0.00% for plasma and -1.4% for urine with a precision of 6.04 and 3.87% for plasma and urine, respectively. The standard curves were linear for both plasma and urine over a wide concentration range (9.96-2490 ng/ml). The plasma method was also applied to measurement of in vitro plasma protein binding of remacemide in rat, dog and human plasma.

Acetamides↗

High-performance liquid chromatographic assay for the simultaneous determination of ethyl clofibrate and clofibric acid in plasma. Evaluation of plasma stability of ethyl clofibrate polylactic nanocapsules in human and rat plasmas.

A rapid, sensitive, and selective HPLC assay was developed for the simultaneous determination of ethyl clofibrate and its major metabolite, clofibric acid, in plasma of humans and rats. The assay involves extraction of the compounds into chloroform-isoamyl alcohol (99:1, v/v) from plasma acidified with sulfuric acid. For human plasma, the overall recoveries of ethyl clofibrate and clofibric acid were 63 and 90%, respectively. The limits of detection of the assay for ethyl clofibrate and clofibric acid in human plasma were 1.1 and 1.5 micrograms/ml, respectively. Limits of quantitation of the assay for ethyl clofibrate and clofibric acid in human plasma were 3.6 and 4.9 micrograms/ml, respectively. The HPLC assay was used to monitor the plasma concentration-time profiles of ethyl clofibrate released from polylactic nanocapsules both in man and rat. The simultaneous determination of ethyl clofibrate and clofibric acid provided evidence that these colloidal systems are stable in human plasma whereas they are lysed in rat plasma.

Animals↗

Plasma catecholamines, plasma renin activity and plasma aldosterone in tetraplegic man, horizontal and tilted.

1. Plasma catecholamines, plasma renin activity, plasma aldosterone and haematocrit were measured in four subjects with physiologically complete cervical spinal cord transections, before, during and after head-up tilt to 45 degrees for 30 min. Plasma catecholamines were measured in five normal male volunteers in the supine position and after head-up tilt to 45 degrees for 10 min. 2. After 10 min of head-up tilt, the plasma noradrenaline rose 14% in the tetraplegic patients and 115% in the control subjects. These findings indicate a failure of sympathetic activity in response to head-up tilt in the tetraplegic patients, probably caused by interruption of pathways by which the brain normally controls sympathetic outflow. 3. In the tetraplegic patients the resting plasma renin activities were above normal, and rose more quickly and greater on head-up tilt than in published studies of normal subjects. It is likely that the renal baroreceptors are important in the control of renin release. 4. In the tetraplegic patients, there was a late rise in plasma aldosterone which was probably due to the elevation in plasma renin activity.

Adult↗

Effects of replacement fluids used for therapeutic plasma exchange on plasma viscosity and plasma oncotic pressure.

INTRODUCTION: Apheresis is a procedure in which one of the components of blood is removed. The aim of therapeutic plasma exchange (TPE) is to remove a large fraction of the patient's plasma from the body, and to exchange this with replacement solutions using automatic devices. With this procedure circulating pathogens and toxins are reduced. Before each TPE results of a baseline basal complete blood count, serum protein electrophoresis, coagulation tests and serum electrolytes must be known. The efficacy of this therapy is assessed only by these values. The proteins responsible for disease may be monoclonal proteins, cryoglobulins, lipoproteins, auto or allo antibodies or toxins. In this study, we aimed to compare the effects of several replacement fluids on plasma viscosity and oncotic pressure. At the same time, we evaluated the correlation between plasma viscosity and oncotic pressure. MATERIAL AND METHODS: 111 TPE were performed on 42 patients. Before TPE, the patients whose veins were not suitable were catheterised either by using a subclavian or jugular 11F dialysis catheter. At each session, approximately 1-1.5L of plasma was exchanged. The procedure was performed with albumin in patients whose albumin was under 3gr/dl. Over this value, the exchange fluids were randomised. RESULTS: When the overall results were analysed, there was no statistically significant difference between groups 1 (HES+albumin) and group 3 (albumin). The statistical difference between group 2 and 3 was significant, but no difference was observed between group 1 and 2. According to the decreasing plasma viscosity, there was a significant difference between group 2 and group 3, but there was no difference between group 1 and group 2. CONCLUSIONS: The replacement solutions used for plasmapheresis are similar when compared for hemorheologic effects, but we have chosen fresh frozen plasma because of fewer side effects.

Adolescent↗

Effects of plasma infusion on plasma lipids, apoproteins and plasma enzyme activities in familial lecithin: cholesterol acyltransferase deficiency.

The siblings presented here are the third family found in Japan with familial LCAT deficiency. Their post-heparin plasma lipoprotein lipase and hepatic triglyceride lipase activities were measured selectively by an immunochemical method. Plasma triglyceride levels were elevated, and post-heparin plasma lipoprotein lipase was decreased only in a patient with nephropathy, while hepatic triglyceride lipase activities were within reference limits in both patients. The plasma concentrations of apo A-I, apo A-II, and apo B were reduced in both patients. On the other hand, the plasma concentration of apo E was markedly increased. Enzyme replacement therapy by plasma transfusion in the propositus resulted in marked improvement of deranged compositions of triglyceride-rich lipoproteins. Also, improvement of the plasma apo E concentration was demonstrated, while the improvement of post-heparin lipase did not occur. These results suggest that LCAT may play an important physiological role in triglyceride metabolism as well as in cholesterol metabolism.

Apoproteins↗

Lack of effect of naloxone in a moderate dosage on the exercise-induced increase in blood pressure, heart rate, plasma catecholamines, plasma renin activity and plasma aldosterone in healthy males.

There is evidence that opioid peptides influence blood pressure and heart rate in animals and man. In the present investigation the effect of naloxone on the exercise-induced increase in blood pressure, heart rate, plasma catecholamines, plasma renin activity (PRA) and plasma aldosterone was investigated in nine healthy men. A submaximal work test was performed on two occasions. The test consisted of ergometer bicycling for 10 min on 50% of maximal working capacity immediately followed by 10 min on 80% of maximal working capacity. Ten minutes before exercise the subjects received in a randomized manner a bolus dose of naloxone (10 micrograms/kg) or a corresponding volume of saline followed by a slow infusion (15 ml/h) of naloxone (5 micrograms h-1 kg-1) or saline, respectively. After exercise systolic blood pressure, heart rate, plasma catecholamines, PRA and plasma aldosterone increased during both saline and naloxone infusion. The changes were similar in both studies. Accordingly, opiate receptors sensitive to naloxone in a moderate dosage seem not to be involved in the cardiovascular response and the increase in plasma catecholamines, PRA and plasma aldosterone induced by exercise.

Adult↗

The concentration of plasma fibronectin in burns patients treated with fresh frozen plasma or plasma protein fraction.

A group of 10 patients with 30-70% burns were given intravenous infusions during the first 48 h following hospital admission either with fresh frozen plasma (FFP) or human plasma protein fraction ( HPPF ). FFP contained 300-400 mg/dl plasma fibronectin whereas none was detectable in HPPF . Circulating plasma fibronectin levels fell quickly in those patients receiving HPPF and levels remained low for 2-3 weeks. In those receiving FFP, plasma fibronectin remained normal during the 48-h transfusion period but fell subsequently. Fibronectin may be an important determinant in the resistance to shock and infections. Consideration should therefore be given to the use of blood products which contain fibronectin and to the monitoring of plasma levels both during the acute and recovery periods after burn injury.

Adolescent↗

Preliminary observations on plasma fibrinogen and plasma protein concentrations and on plasma protein:fibrinogen ratios in clinically healthy buffaloes.

The plasma fibrinogen concentration, the total plasma protein concentration and the plasma protein to fibrinogen ratio (PP:F) were determined in clinically healthy Nili Ravi buffaloes. The plasma fibrinogen concentrations in calves, lactating and non-lactating buffaloes were 513 +/- 62, 615 +/- 90 and 544 +/- 74 mg/dl, respectively, and were statistically different (p < 0.05). Total plasma protein concentrations in these animals were 7.15 +/- 0.28, 9.32 +/- 0.53 and 8.79 +/- 0.58 g/dl. PP:F for all animals was between 11 and 19. Fibrinogen levels were positively correlated with plasma protein (r = 0.59) and negatively correlated with PP:F (r = -0.59).

Animals↗

Plasma calcium control in the rat fetus. III. Influence of alterations in maternal plasma calcium on fetal plasma calcium level.

Acute maternal alterations in plasma calcium were used as an indirect mean to study the placental transfer of calcium in thyroparathyroidectomized (TPTX) pregnant rats. Calcium infusions to normal or TPTX females showed in both cases a saturation mechanism reflected on fetal plasma calcium. With TPTX mothers saturation curves of the fetal plasma calcium were similar whether fetuses were decapitated (deprived of brain, hypophysis, and thyroparathyroid complex) or intact. Increments in fetal plasma calcium were 4-fold higher in TPTX mothers (approximately 2.5 mg/dl), and 2-fold higher in thyroidectomized (TX) mothers (approximately 0.5 mg/dl). From the whole results, it appeared that increments in fetal plasma calcium secondary to maternal calcium infusion were probably related to the basal plasma calcium in the fetus, and not to the hormonal deficiency of the mother.

Animals↗

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↗