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PubMed1976

Endocrine and environmental influences upon plasma cortisol concentrations and plasma renin activity of the eel, Anguilla anguilla L.

The plasma concentrations of cortisol, sodium, potassium and calcium and plasma osmolarity were determined in freshwater silver eels, after intravascular injections of eel renin preparations, mammalian ACTH, mammalian angiotensin II and eel muscle extracts. Arterial blood specimens were taken before and after injection of test substances. Partially purified eel and rat renal renins gave prolonged pressor responses in intact and hypophysectomized eels and in the nephrectomized rat anaesthetized with sodium pentobarbitone. Angiotensin, but not ACTH, produced obvious pressor responses in intact and hypophysectomized eels and in eels without their corpuscles of Stannius. Hypophysectomized eels 4-8 days after operation had reduced plasma cortisol concentrations. No change in cortisol occurred in eels after removal of the corpuscles of Stannius. Eel renin preparations and ACTH gave increased concentrations of plasma cortisol 30 min after injection into hypophysectomized and intact eels. In general, the length of the renin-generated pressor response and the increased cortisol concentration were concomitant occurrences. Angiotensin injected into eels with corpuscles of Stannius removed and into hypophysectomized eels also increased cortisol levels. Control muscle extracts produced no significant changes. There were no acute changes in plasma electrolyte concentrations after the injections. Plasma renin activity measured indirectly by bioassay of angiotensin generated in vitro was more than twice as great in eels adapted to seawater than in eels in fresh water. Plasma renin activity gradually fell when eels were transferred from seawater to fresh water, and increased when the reverse transfer was carried out.

Adaptation, Physiological↗
PubMed1986

Control of sex steroid-binding protein (SBP) in the male little brown bat: relationship of plasma thyroxine levels to the induction of plasma SBP in immature males.

The seasonally reproductive male little brown bat (Myotis lucifugus lucifugus) exhibits marked increases in plasma concentrations of sex steroid-binding protein (SBP) in the spring following arousal from hibernation. In this species an increase in SBP levels is induced prematurely in male bats aroused during the first half of hibernation and housed under long photoperiods; however, this rise is inhibited in bats housed under short photoperiods. In order to investigate the physiological role of the thyroid gland in the regulation of plasma SBP activity, plasma total thyroxine (T4) and SBP concentrations were determined in immature male little brown bats prematurely aroused from the first half of hibernation and maintained on either a short or long photoperiod. For this purpose a radioimmunoassay for the measurement of total T4 in bat plasma was established and validated. The results showed that immature male little brown bats aroused prematurely from hibernation and housed under a long spring-like photoperiod exhibited marked increases in plasma T4 and SBP concentrations, while animals housed under a short photoperiod showed only marginal increases in SBP, and plasma T4 remained undetectable. These results suggest that the thyroid gland, through the action of T4, may normally play an important role in the control of the post-arousal rise in plasma SBP concentrations in the little brown bat.

Animals↗
PubMed1996

Influence of insulin-like growth factor-binding protein-2 on plasma clearance and transfer of insulin-like growth factors-I and -II from plasma into mammary-derived lymph and milk of goats.

Plasma clearance of insulin-like growth factors-I and -II (IGF-I and -II) and insulin-like growth factor-binding protein-2 (IGFBP-2) from lactating goats (n = 4) was determined following a single intravenous injection of the corresponding 125I-labelled human protein. Transfer of these proteins out of the vascular space was monitored by their subsequent appearance in mammary-derived lymph and milk. Clearance of 125I-IGFBP-2 from circulation was 0.37 +/- 0.06 ml/min/kg, which is markedly greater than that of 125I-IGF-I or -II (0.11 +/- 0.01 and 0.12 +/- 0.01 ml/min/kg respectively). This was also reflected in longer elimination half-lives for IGF-I (353 +/- 6 min) and -II (254 +/- 8 min) compared with IGFBP-2 (110 +/- 9 min). Three hours after injection of the 125I-labelled protein, the plasma:lymph ratio of trichloroacetic acid-precipitable radioactivity was 1.54 +/- 0.04, 3.3 +/- 0.6 and 4.1 +/- 0.4 for IGFBP-2, IGF-I and -II respectively. The form of 125I-IGFBP-2 in lymph was not different from that of plasma. Elevation of plasma concentrations of IGFBP-2 by its intravenous infusion significantly decreased plasma half-life of both IGF-I and -II (251 +/- 8 and 198 +/- 7 min respectively). Although the amount and rate of transfer of IGF into mammary-derived lymph was decreased slightly by IGFBP-2, concentrations eventually obtained were not different from control. However, secretion of IGFs into milk was significantly reduced by IGFBP-2, particularly in the case of IGF-I. These results are consistent with the ability of all three compounds to cross the vascular endothelium intact and of IGFBP-2 to decrease the uptake of IGF by mammary epithelium and subsequent secretion into milk. IGFBP-2 may well have acted to target plasma IGF towards non-mammary tissues, thus explaining the more rapid plasma clearance of IGFs in the presence of elevated IGFBP-2.

Animals↗
PubMed1995

Plasma protein for pigs weaned at 19 to 24 days of age: effect on performance and plasma insulin-like growth factor I, growth hormone, insulin, and glucose concentrations.

Three experiments were conducted to evaluate spray-dried porcine plasma (SDPP) protein in diets for early weaned pigs. In Exp. 1, 144 weanling pigs (24 +/- 4 d of age) were used to determine the effects of replacing dried skim milk (DSM) with either 4% SDPP or 2.75% spray-dried blood meal (SDBM) in Phase 1 diets (d 0 to 14 postweaning). During 0 to 14, pigs fed SDPP or SDBM had higher ADG (P < .05) and ADFI (P < .1) than those fed DSM. Pigs fed SDPP had greater (P < .05) ADG and ADFI (P < .1) than those fed SDBM. In Exp. 2, performance was similar in pigs fed two plasma protein sources (AP-820 and MP-722). In Exp.3, 18 weanling pigs (19 to 20 d of age) were used to determine the effects of feeding high levels of SDPP on performance and on plasma IGF-I, growth hormone, insulin, and glucose concentrations. Pigs were fed either a control diet containing 21.5% soybean meal (SBM) or a diet containing 14% SDPP. Treatments were applied for 14 d (Phase 1). During d 0 to 14, pigs fed a SDPP had a greater ADG and ADFI (P < .05) than pigs fed SBM. Replacing SBM with SDPP did not affect plasma IGF-I and glucose concentrations. However, SDPP replacement increased (P < .06) plasma growth hormone concentrations. Insulin levels were greater (P < .06) in pigs fed SBM than in those fed SDPP. These results indicate that SDPP and SDBM are effective alternatives to DSM or SBM in Phase 1 diets and the two plasma protein sources will produce similar performance. The factor(s) responsible for this improved performance does not seem to involve a change in plasma IGF-I.

Aging↗
PubMed1992

Proton magnetic resonance spectroscopy of fractionated plasma lipoproteins and reconstituted plasma from healthy subjects and patients with cancer.

Proton nuclear magnetic resonance spectra at 500 MHz of plasma and the very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fractions isolated by KBr gradient ultracentrifugation were analysed in 16 cancer patients, six pregnant and nine non-pregnant healthy subjects. In spectra with narrow plasma composite aliphatic peaks (methylene at 1.2-1.4 p.p.m. and methyl at 0.8-0.9 p.p.m., respectively), a relative increase in either VLDL, LDL, or both, or a decrease in HDL signals was observed. The mechanism for line-width narrowing seemed different in cancer patients (less signals from HDL relative to VLDL) compared with pregnant women (more signals from LDL). By reconstitution of plasma samples from both healthy subjects and patients with malignant disease, decreased concentration of VLDL or HDL resulted in broadening or narrowing of the composite peaks, respectively. The effects of VLDL and HDL on the plasma line width were moderated by the signals from LDL. Within lipoprotein fractions, the methylene and methyl resonances were shifted to a higher field with increased observation temperature, the change in shift being greatest for HDL. The line width of composite peaks in plasma varied with the observation temperature, depending on the relative concentrations of individual lipoproteins. The correlation coefficient (r) for the relation between total plasma triglyceride level and the average of the line-width of the composite methylene and methyl peaks was -0.78 (p less than 0.001). For spectra of individual lipoproteins, statistical significant relationships were found between line-widths and triglyceride content of the LDL fraction (methyl line-width, r = -0.63) (p less than 0.001) and between methylene line-width and cholesterol of HDL (r = 0.54) (p = 0.003). In summary, the shape and width of the composite aliphatic peaks of plasma were affected by the relative concentration, chemical shift and transition temperature of both VLDL, LDL, and HDL, and by the total triglyceride level. Comparing pregnancy and malignant disease, the lipoprotein resonances contributed differently in giving narrow composite signals.

Female↗
PubMed2000

A prospective study of CD38/45 flow cytometry and immunofluorescence microscopy to detect blood plasma cells in patients with plasma cell proliferative disorders.

Malignant plasma cells can be detected in the blood of patients with multiple myeloma (MM) using flow cytometry (FC), immunofluorescence microscopy (IM), or a variety of molecular techniques. Increased numbers of light chain-restricted blood plasma cells as detected by IM is associated with a diagnosis of overt MM and a decreased overall survival. The IM technique is time consuming; therefore, a prospective study was designed to test whether CD38 CD45 FC could simplify the procedure. Blood samples from 769 patients with plasma cell proliferative disorders were studied prospectively by FC and IM over a one-year period. The FC technique was performed on 1 ml of whole blood after ammonium chloride red blood cell lysis and utilized anti-CD38PE and anti-CD45PerCP. The number of CD38+ 45- events were enumerated and compared to the number of light chain-restricted plasma cells detected by the standard IM technique. In 46% (353/769) of cases > or = 1 CD38+ CD45- events were detected by FC whereas IM was positive for light chain restricted plasma cells in 33%; there was concordance between FC and IM in 73% of cases. In 20% of cases FC was positive and IM was negative; however, in 7% of cases FC was negative yet light chain-restricted plasma cells were detected by IM. FC was positive in 88% (134/153) of cases where the IM technique showed a high number of circulating plasma cells. This study demonstrates that two-color CD38/45 FC identifies most cases with a high IM result and reduces the workload in the clinical laboratory. The prognostic implications of a positive FC screen but a negative IM will require long-term patient follow-up.

ADP-ribosyl Cyclase↗
PubMed1982

Activation of plasma prorenin by plasminogen activators in vitro and increase in plasma renin after stimulation of fibrinolytic activity in vivo.

Plasminogen can be activated by intrinsic activators that circulate in plasma in a precursor form, by extrinsic activator originating from tissues or the vessel wall and by the exogenous activators, urokinase and streptokinase. Tissue activator and vascular activator are probably identical. Dialysis of plasma against pH 4.0 buffer causes denaturation of the plasmin inhibitors, alpha 2-antiplasmin and C1-inhibitor, while alpha 2-macroglobulin is left intact. Incubation of pH 4.0-pretreated plasma with urokinase or streptokinase at pH 7.5 led to activation of plasminogen and prorenin. Incubation of a plasma fraction, which contained plasminogen and prorenin but no alpha 2-antiplasmin and renin, with highly purified tissue plasminogen activator also led to activation of prorenin. The vasopressin analogue, 1-desamino-8-D-arginine vasopressin (DDAVP), is a potent stimulant for the release of extrinsic activator into the bloodstream. After infusion of DDAVP, 0.4 micrograms/kg, into normal subjects, parallel increments in plasma fibrinolytic activity and renin were observed. Infusion of DDAVP into patients with type IV hyperlipoproteinaemia had little effect on plasma fibrinolytic activity and the response of plasma renin was also subnormal. These observations warrant further studies on a possible role for plasminogen activators in prorenin activation in vivo.

Cold Temperature↗
PubMed1995

Oxidatively modified plasma phospholipids containing reactive carbonyl functions measured by HPLC: evidence for phosphatidylcholine-bound aldehydes in plasma of burn patients.

A HPLC method has been developed to measure phosphatidylcholine (PC) containing reactive carbonyl functions in the sn-acyl residue in order to study processes in which such reactive carbonyls can be formed due to e.g. oxidative fragmentation. The method has been applied to determine PC-bound carbonyls as 2,4-dinitrophenylhydrazones (DNPH) in plasma of burn patients. Plasma from healthy volunteers served as controls. Additionally, in vitro oxidation experiments (A: plasma, buffer diluted; B: plasma + iron-EDTA complex and C: plasma + iron-EDTA complex + H2O2) have been performed to obtain and to identify 2,4-dinitrophenylhydrazine derivatizable carbonyl functions in plasma PC. Both, the PC-aldehydes and PC-aldehyde DNPH derivatives were cleavable with phospholipase C. Quantification was based on thin-layer chromatography purified soybean phosphatidylcholine, which was identically oxidized and derivatized as the plasma lipids in vitro.

Adult↗
PubMed2002

Association of beta-fibrinogen and factor VII polymorphism with plasma fibrinogen and factor VII levels, and no association of PAI-1 polymorphism with plasma PAI-1 levels in hemodialysis patients.

AIMS: Recent studies have stressed the roles of genetic factors on the plasma levels of hemostatic markers and on cardiovascular complications. We investigated the association of DNA polymorphisms for beta-fibrinogen, factor VII, and PAI-1 with plasma levels of these factors and with ischemic heart disease (IHD) and cerebral infarction (CI) in patients undergoing hemodialysis (HD). METHODS: beta-fibrinogen G/A-455, factor VII R353Q and PAI-1 4G/5G polymorphisms were determined by PCR-RFLP in 149 HD patients and in 100 controls. The plasma levels of fibrinogen, factor VII and PAI-1 were also measured. RESULTS: The allele frequencies and the genotype frequencies of these 3 polymorphisms were not different between HD patients and controls. In HD patients, plasma fibrinogen levels were significantly lower in the GG genotype than in the GA genotype, and plasma factor VII activity was significantly higher in the RR genotype than in the RQ genotype. Multiple regression analysis disclosed that CRP and beta-fibrinogen polymorphism were the significant determinants of fibrinogen levels. Plasma PAI-1 levels were not different among the 3 genotypes. The frequency of the A-455 allele was significantly higher in HD patients with CI than in those without CI, and the genotype distribution for beta-fibrinogen differed significantly between the 2 groups. Between the same 2 groups, however, significant differences were found neither in the frequency of the 353Q or 4G allele nor in the genotype distribution for factor VII and PAI-1. No significant differences in the frequency of the G-455, 353Q or 4G alleles, or in the genotype distribution for beta-fibrinogen, factor VII and PAI-1 were observed between patients with IHD and those without IHD. Multiple logistic regression analysis demonstrated that neither polymorphism was associated with CI or IHD. CONCLUSIONS: In HD patients, beta-fibrinogen and factor VII polymorphisms affected plasma levels of fibrinogen and factor VII, respectively. Beta-fibrinogen polymorphism was not an independent but a possible risk factor for CI in HD patients. Further study will be needed to confirm the precise role of 5-fibrinogen polymorphisms in the pathogenesis of CI in HD patients.

Adult↗
PubMed1999

Comparison of microbiologic and high-performance liquid chromatography assays to determine plasma concentrations, pharmacokinetics, and bioavailability of erythromycin base in plasma of foals after intravenous or intragastric administration.

OBJECTIVE: To determine pharmacokinetics and bioavailability of erythromycin base after intragastric administration and erythromycin lactobionate after IV administration to healthy foals and to compare a microbiologic assay with a high-performance liquid chromatography (HPLC) method to determine plasma concentrations of erythromycin A. ANIMALS: 6 healthy foals that were 2 to 4 months old. PROCEDURE: Foals were given single doses of erythromycin (10 mg/kg of body weight, IV, and 25 mg/kg, intragastrically) in a crossover study. Venous blood samples were obtained at specific times after drug administration, and plasma was harvested for determination of erythromycin concentrations by microbiologic assay and a HPLC method Pharmacokinetic analysis of plasma concentration-time data was performed, and results derived from each method were compared. RESULTS: Concentration-time profiles for IV administration were best described by a two-compartment open model. Comparing pharmacokinetic data obtained by the 2 methods revealed substantial differences in results. Values for area under the plasma concentration-time curve and area under the first moment of the curve were substantially higher when determined by the bioassay, indicating overestimation of plasma concentration-time data by this method. The derived rate transfer constants (K21 and K(e)1) and mean residence time were significantly different, when determined by the bioassay. Systemic bioavailability of erythromycin base was low in all foals. CONCLUSIONS AND CLINICAL RELEVANCE: The bioassay method overestimated plasma concentrations of erythromycin, compared with the HPLC method. Despite low systemic bioavailability of erythromycin base administered intragastrically, plasma concentrations of erythromycin exceeded, for at least 4 hours, the minimum inhibitory concentration of most Rhodococcus equi isolates.

Animals↗
PubMed1999

Plasma pyridoxal phosphate and pyridoxic acid and their relationship to plasma homocysteine in a representative sample of British men and women aged 65 years and over.

Concentrations of pyridoxal phosphate and pyridoxic acid were measured in fasting plasma samples from British men and women aged 65 years and over, participating in a National Diet and Nutrition Survey during 1994-5, selected to be representative of the population of mainland Britain. In this population, the concentration of pyridoxal phosphate declined, whereas pyridoxic acid rose, with increasing age and frailty; however, both status indicators were strongly and directly (with a positive coefficient) correlated with estimates of vitamin B6 intake. This was little affected by the inclusion of food energy and protein intakes in the model. Forty-eight percent of the participants living in the community and 75% of those living in institutions had plasma pyridoxal phosphate concentrations below a range considered normal from other studies. In a univariate regression model, plasma pyridoxal phosphate concentrations were inversely correlated with plasma homocysteine concentrations, consistent with the hypothesis that vitamin B6 status may influence plasma homocysteine levels, and hence vascular disease risk. However, this relationship was partly attenuated in a multiple regression model including age, sex, domicile and biochemical status indices, including those of folate and vitamin B12. There was evidence that plasma pyridoxal phosphate was sensitive to metabolic conditions associated with inflammation and the acute-phase reaction, and that plasma pyridoxic acid was sensitive to renal function. Thus, neither index is an ideal predictor of vitamin B6 status in older people, unless these confounding factors are allowed for. Since poor vitamin B6 status may have health implications, e.g. for immune function, cognition, and for essential intermediary metabolic pathways in older people, it needs to be investigated as a possible public health problem.

Adolescent↗
PubMed2000

Monitoring hypocoagulant conditions in rat plasma: factors determining the endogenous thrombin potential of tissue factor-activated plasma.

Automated human plasma, continuous monitoring of the formation and inactivation of thrombin during the coagulation process provides an adequate way to detect hypo- and hypercoagulant conditions. Here, we describe an analogous procedure to determine the endogenous thrombin potential (ETP), i. e. the free thrombin concentration-time integral, of coagulating rat plasma. When activated with tissue factor, the ETP of plasma from Wistar rats was comparable to the ETP of human plasma, in spite of a relatively short half-life time of free thrombin in rat plasma. The ETP was highly sensitive to heparin as well as to administration of vitamin K antagonist or feeding of the animals with a vitamin K-deficient diet. In plasma that was activated under sub-optimal conditions (reduced levels of tissue factor or vitamin K-dependent coagulation factors), the ETP increased with the rate of thrombin formation in the first minutes of the coagulation process. Since both parameters are dependent of the prothrombin concentration, it appears that this level plays an important role in determining both the initial and total activity of the coagulation system. Thus, automated measurement of free thrombin during the coagulation process of rat plasma allows a detailed analysis of hypocoagulability in this animal model.

Animals↗
PubMed2001

The level and species of plasma non-esterified fatty acids are not related to elevated plasma apolipoprotein B levels in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL), the leading cause of familial hyperlipidemia with premature coronary artery disease, has been associated with insulin resistance and elevated plasma levels of apolipoproten B (apoB) and non-esterified fatty acids (NEFA). Becaus dietary fats affect plasma cholesterol levels, and specific saturated fatty acids (FA) are particularly potent stimulators in vitro of apoB secretio from hepatocytes, we hypothesized that FCHL patients would exhibit elevations in plasma levels of total FA or specific saturated species. Five families containing 12 FCHL subjects (5 adults, 7 children and 8 normals (5 adults, 3 children) were assessed by dietary, anthropometric, and plasma measurements (glucose, insulin, lipoproteins, total NEFA, and specific FA types). After adjustment of the data for age, gender, and family affiliation, multivariate ANOVA indicated that FCHL was significantly associated with elevated plasma levels of apoB (p = 0.001) and insulin (p< 0.001) and increased body weight (p=0.043). Nevertheless, dietary intakes of total and saturated fat were comparable in the two groups, as were plasma levels of total NEFA and the major saturated species. In a study population possessing the salient features of FCHL, circulating total NEFA were not elevated, nor were specific saturated NEFA that had been associated with apoB oversecretion in vitro. Despite the speculated link between plasma FA and apoB overproduction in FCHL, our data suggest that other metabolic factors underlie this disease.

Adult↗
PubMed2002

Low plasma antioxidants and normal plasma B vitamins and homocysteine in patients with severe obesity.

BACKGROUND: Obesity is among the well-established risk factors for cardiovascular morbidity and mortality. However, the exact mechanisms are not well understood. Low concentrations of vitamins (fat soluble antioxidants and B vitamins) are linked to accelerated atherosclerosis through increased oxidative stress and homocysteine. OBJECTIVE: To compare plasma antioxidant vitamins (carotenoids and vitamin E), B vitamins (folic acid and B12) and homocysteine--all linked to increased cardiovascular morbidity--between patients with severe obesity and lean control subjects. METHODS: We investigated plasma carotenoids, vitamin E, folic acid, B12, and homocysteine in 25 obese patients and their age-matched controls (body mass index 38 +/- 3 vs. 21 +/- 2 kg/m2), respectively), related to BMI and plasma insulin. RESULTS: Patients with obesity had normal B vitamins and a non-significant decrease in plasma homocysteine as compared to controls (9.4 +/- 2.6 vs. 11.4 +/- 4.8 mumol/L, P = 0.07). There was a significant decrease in both plasma carotenoids and vitamin E (0.69 +/- 0.32 vs. 1.25 +/- 0.72 and 24 +/- 10 vs. 33 +/- 14 micrograms/ml, respectively; P < 0.01). Both vitamins were inversely related to BMI and plasma insulin, which was significantly increased in patients with obesity (22 +/- 21 vs. 6 +/- 2 microU/ml, P < 0.01). CONCLUSIONS: Obese patients with BMI above 35 kg/m2 show low plasma antioxidants (carotenoids and vitamin E). This may result in increased oxidative stress and consequently enhanced atherosclerosis in these patients.

Adult↗
PubMed1992

Isolation of plasma membranes, Golgi bodies and mitochondria of Xenopus laevis morulae. Identification of plasma membrane proteins.

Homogenates of Xenopus morulae at the 16-32 cell stage were centrifuged on discontinuous sucrose gradients. Isolated fractions were identified by electron microscopy (EM) as mitochondria, a fraction enriched in Golgi vesicles, and plasma membranes. A special effort was made to prepare plasma membranes free of cytoplasmic contaminants. The resulting purified plasma membranes appeared morphologically identical to plasma membranes in situ. The external surface is covered with a fibrillar coat while vesicles are seen attached to their inner surface. O'Farell's method (1975) was used to obtain protein patterns of the various fractions on 2-dimensional gel electrophoresis. Each fraction displayed a specific pattern. By comparing the different patterns, it was possible to identify a group of proteins as belonging to the plasma membrane fractions. Labelling of cell surface with sulfo-N-hydroxysuccinimido-biotin together with differential extraction of proteins has allowed us to tentatively allocate these proteins in different structures of the plasma membrane fractions. The data presented in this paper corroborate and extend our ultrastructural studies on neogenesis of interblastomeric plasma membranes (Bieliavsky and Geuskens, 1990).

Animals↗
PubMed1991

Inhibition of extrinsic pathway inhibitor shortens the coagulation time of normal plasma and of hemophilia plasma.

An increasing amount of evidence suggests that coagulation factors VIII and IX play a role not only in the intrinsic but also in the extrinsic pathway of coagulation. In this context the influence of the Extrinsic Pathway Inhibitor (EPI) on the coagulation time of hemophilia plasma lacking FVIII or FIX has been investigated. The coagulation time was measured in a dilute thromboplastin assay. Addition of recombinant EPI (rEPI) prolonged the coagulation time of normal plasma while the addition of an inhibitory antibody against EPI shortened the coagulation time. At low concentrations of thromboplastin the coagulation time of hemophilia plasma was prolonged and at all dilutions of thromboplastin, addition of anti-EPI IgG normalized the coagulation time of a hemophilia plasma. Analysis of 10 individual donor plasma samples and 8 individual hemophilia samples showed that addition of anti-EPI IgG shortened the coagulation time more in hemophilia plasma than in normal plasma. This illustrates the importance of a powerful extrinsic FVII dependent pathway to achieve hemostasis in the case of FVIII or FIX deficiency (hemophilia A and B).

Antibody Specificity↗
PubMed1991

Interaction of plasma kallikrein with protein C inhibitor in purified mixtures and in plasma.

The interaction between plasma kallikrein (KK) and protein C inhibitor (PCI) and the influence of KK on the complex formation between activated protein C (APC) and PCI was studied in purified systems as well as in plasma in order to assess the significance of these reactions in the plasma milieu. PCI complexed to KK (KK:PCI) or to APC (APC:PCI) was measured by sandwich ELISA's using antibodies directed against each protein in the complexes. The formation of KK:PCI complexes assayed by this method paralleled the inhibition of KK amidolytic activity by PCI in purified system. Incubation of normal plasma (NHP) at 4 degrees C, which can induce prekallikrein activation due to cold activation, resulted in PCI inactivation and appearance of KK:PCI complexes. PCI activity fell to 35% of the NHP and 1.2 micrograms/ml of KK:PCI complex was formed. However, incubation of NHP at room temperature or of prekallikrein deficient plasma at 4 degrees C did not result in significant decrease of PCI activity. Thus the PCI inactivation was associated with prekallikrein activation and complexation to PCI following cold activation. Incubation of exogenous purified KK with NHP resulted in PCI inactivation and complexation with KK in a temperature-dependent manner. Addition of 2.8 micrograms/ml KK to plasma at 4 degrees C resulted in the inactivation of 55% of plasma PCI and the formation of 0.9 microgram/ml KK:PCI which represents 21% of the KK added, whereas at 37 degrees C PCI was inactivated to 30% and only 0.30 microgram/ml KK:PCI complexes were measured. These results indicate that PCI is a major KK inhibitor at 4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1991

Plasma renin activity and plasma prorenin assays.

Sensitivity and accuracy are essential features of an assay of plasma renin activity (PRA) because the normal concentration of PRA is only 1 pmol/L, and subnormal concentrations have diagnostic relevance. Conditions for blood collection need to be standardized but the conditions are not difficult for outpatients. For routine diagnostic purposes blood should be collected from ambulatory (ideally, untreated) patients on moderate sodium intake. To avoid irreversible cryoactivation of plasma prorenin (which is present in 10-fold greater concentrations than renin), samples should be processed at room temperature and stored completely frozen. Cryoactivation occurs when plasma is liquid at temperatures less than 6 degrees C. PRA is commonly measured with an enzyme kinetic assay in which angiotensin I (Ang I) is formed by the reaction of plasma renin with endogenous renin substrate (angiotensinogen). The Ang I so formed is measured by RIA; results are expressed as an hourly rate (micrograms/L formed per hour). This method, which is provided by most commercial kits, has the potential for unlimited sensitivity because the step for Ang I generation can be prolonged as long as necessary, so that enough Ang I forms to be measured accurately. Unfortunately, that sensitivity is not always exploited. Dilution of plasma during pH adjustment should be kept to a minimum. The Ang I generation step should last at least 3 h. The step should last 18 h for samples with PRA less than 1.0 micrograms/L per hour, to eliminate the errors inherent in the measurement and subtraction of immunoreactive Ang I in the untreated plasma (blank subtraction). These changes actually simplify PRA measurements because they eliminate the need for ice in the clinic and reduce by almost half the number of samples to be assayed by RIA. I also describe the method for measurement of plasma prorenin, which may be an important marker for patients with diabetes mellitus who subsequently develop vascular complications.

Angiotensin I↗