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PubMed1976

Plasma insulin concentration during physiological variations in immunoreactive plasma secretin.

The effect of endogenous and exogenous secretin on fasting plasma insulin and glucose concentrations in peripheral venous blood was studied. In 10 non-diabetic subjects intragastric instillation of 300 ml 0.1 mol/l hydrochloric acid increased the plasma secretin concentration significantly. This increment did not influence insulin or glucose concentration. Control experiments with intragastric instillation of 300 ml of isotonic saline did not influence the plasma concentration of secretin, insulin or glucose. In four other non-diabetic persons no significant changes were found in plasma insulin or glucose concentration during an i.v. infusion of pure natural porcine secretin in doses of 0.1, 0.3, 1.0 and 3.0 clinical units/kg/h. The results suggest that secretin is without effect on insulin secretion in the fasting normal subject.

Adult↗

PubMed1984

Plasma dehydroepiandrosterone, dehydroepiandrosterone sulphate and androsterone sulphate levels and their interaction with plasma proteins in rheumatoid arthritis.

Female patients with rheumatoid arthritis (RA) in Steinbrocker's II and III rating scale have been examined. They were without steroid treatment at least six months before observation. Plasma protein picture showed hypoalbuminaemia and hyperglobulinaemia. There was no difference relative to controls either in the total (free + protein bound) plasma dehydroepiandrosterone (D) level, or in its distribution with plasma proteins. In the age group of 18 to 45 years, a statistically significant decrease have been observed in the total plasma dehydroepiandrosterone sulphate (DS) level without any change in its distribution in protein binding. Furthermore, low androsterone sulphate (AS) levels were found irrespective of the age of patients. The results gave further information on the pathomechanism resulting in an abnormal androgen hormone pattern of blood and a low metabolite excretion, observed previously in patients with RA:.

Adolescent↗

PubMed1986

The effects of oral agent or insulin treatments on the plasma lipoproteins and the plasma lipoprotein lipase activator in diabetic patients.

The structure and the metabolism of plasma lipoproteins are altered in diabetes mellitus. Insulin or oral agent treatments affect the lipoprotein metabolism in addition to improving hyperglycemia. However, it is not clear whether the alterations seen in lipoproteins during treatment are related to the degree of diabetic control or to the mode of diabetic treatment. The effects of insulin or oral agent treatments on the plasma lipoproteins and lipoprotein lipase activator were compared in a strictly defined non-obese, non-insulin dependent diabetic patient. Both treatment groups had similar plasma triglyceride, total cholesterol, low and high density lipoprotein cholesterol, and lipoprotein lipase activator levels. Lipoprotein lipase activator contents of the very low density lipoproteins correlated positively with their triglyceride (r = 0.803 in insulin, r = 0.828 in oral agent treated patients) and protein (r = 0.713 in insulin, r = 0.862 in oral agent treated patients) contents. The findings of this study indicated that plasma lipid levels, very low density lipoprotein compositions, and lipoprotein lipase activator contents were not significantly different in non-obese, non-insulin dependent diabetic patients treated with either oral hypoglycemic agents or insulin.

Administration, Oral↗

PubMed2002

Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole.

OBJECTIVE: Our objective was to examine the effects of itraconazole on the pharmacokinetics and cortisol-suppressant activity of budesonide administered by inhalation. METHODS: In a randomized, double-blind, 2-phase crossover study, 10 healthy subjects took 200 mg itraconazole or placebo orally once a day for 5 days. On day 5, 1 hour after the last dose of itraconazole or placebo, 1000 microg budesonide was administered by inhalation. Plasma budesonide and cortisol concentrations were measured up to 23 hours. RESULTS: Itraconazole increased the mean total area under the plasma concentration-time curve of inhaled budesonide 4.2-fold (range, 1.7-fold to 9.8-fold; P <.01) and the peak plasma concentration 1.6-fold (P <.01) compared with placebo. The mean terminal half-life of budesonide was prolonged from 1.6 to 6.2 hours (ie, 3.7-fold; range, 1.5-fold to 9.3-fold; P <.001) by itraconazole. The suppression of cortisol production after inhalation of budesonide was significantly increased by itraconazole as compared with placebo, as shown by a 43% reduction in the area under the plasma cortisol concentration-time curve from 0.5 to 10 hours (P <.001) and a 12% decrease in the cortisol concentration measured 23 hours after administration of budesonide, at 8 am (P <.05). CONCLUSIONS: Itraconazole markedly increased systemic exposure to inhaled budesonide, probably by inhibiting the cytochrome P4503A4-mediated metabolism of budesonide during both the first-pass and the elimination phases. This interaction resulted in enhanced systemic effects of budesonide, as shown by suppression of cortisol production. Long-term coadministration of budesonide and a potent CYP3A4 inhibitor may be associated with an increased risk of adverse effects of budesonide.

Administration, Inhalation↗

PubMed1995

Passive immunotherapy in AIDS: a double-blind randomized study based on transfusions of plasma rich in anti-human immunodeficiency virus 1 antibodies vs. transfusions of seronegative plasma.

A randomized double-blind controlled trial was conducted to determine the efficacy of passive immunotherapy in the treatment of symptomatic human immunodeficiency virus (HIV) infection. This trial included 86 symptomatic patients randomized to receive plasma rich in anti-HIV-1 antibody or standard seronegative plasma. Each patient in both groups received a 300-ml infusion every 14 days over a 1-year period, and every 28 days thereafter, in addition to zidovudine and other conventional prophylactic treatments. Plasma donors were selected among symptomless seropositive individuals with a CD4 lymphocyte count > or = 400 x 10(6) cells per liter, a negative p24 antigen assay, and a high concentration of anti-p24 antibody. The plasmas were heat-inactivated before infusion. During the study period (day 28-day 365) scheduled by the protocol, clinical benefit from passive immunotherapy was observed in delaying the appearance of the first AIDS-defining event (P < 0.009) and reducing the cumulative incidence of such events, which was estimated 3-fold higher in the control group compared to the treatment group. Seven deaths occurred in the treatment group vs. 11 in the control group (P = 0.27). A total of 47 patients died or exhibited new AIDS-defining events, 18 in the treatment group and 29 in the control group (P = 0.009). No clinical benefit was observed after the 1-year period with infusions performed every 4 weeks. These results indicate a favorable effect of passive immunotherapy on the evolution of advanced AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Plasma concentrations of artemether and its major plasma metabolite, dihydroartemisinin, following a 5-day regimen of oral artemether, in patients with uncomplicated falciparum malaria.

Plasma concentrations of artemether and its active plasma metabolite (dihydroartemisinin) were measured in 49 male, Thai patients with acute, uncomplicated, multidrug-resistant, Plasmodium falciparum malaria, following their treatment with oral artemether (300 mg on the first day, then 100 mg daily for another 4 days). Four patients recrudesced (on days 19-22). After the first dose, artemether became undetectable in < or = 18 h and this drug was also undetectable in samples collected immediately before each dose. Although dihydroartemisinin followed similar trends, three patients had detectable plasma concentrations of this metabolite 24 h after the first dose (i.e. immediately before the second dose). Median (range) values for plasma concentrations of dihydroartemisinin 6 h [354 (150-751) v. 196 (178-220) ng/ml] and 12 h [158 (25-420) v. 54 (25-115) ng/ml] after the initial dose, estimated antimalarial activities (calculated as dihydroartemisinin equivalents) 6 h [331 (78.2-644.1) v. 23 (183.3-270) nmol/litre] and 12 h [98.3 (10-192.2) v. 56.7 (9.8-59.4) nmol/litre] after the initial dose, and the corresponding 'areas under the curves' (AUC) [3684 (1562-8216) v. 834 (1401-2030) ng.h/ml] were all significantly higher in the patients with sensitive responses than in those who recrudesced.

Acute Disease↗

PubMed2001

Evaluation of plasma 3,4-dihydroxyphenylacetic acid (DOPAC) and plasma 3,4-dihydroxyphenylalanine (DOPA) as tumor markers in children with neuroblastoma.

Catecholamines and their metabolites are important in the diagnosis of neuroblastoma (NB). Plasma (p-) levels of 3,4-dihydroxyphenylalanine (DOPA) are increased in most NB, probably reflecting decreased DOPA decarboxylase activity. Urine (u-) homovanillic acid (HVA), a DOPA and dopamine (DA) metabolite. is also increased in most NB. DOPAC (3,4-dihydroxyphenylacetic acid) is an important metabolite of DA in tissues with monoamine oxidase (MAO) activity. Because MAO is expressed in NB tumor cells, we studied the importance of measuring p-DOPAC and p-DOPA as compared to u-HVA and u-vanillylmandelic acid (VMA) in the diagnosis and follow-up of NB. DOPAC, DOPA, dopamine, noradrenaline, adrenaline, VMA and HVA were measured by reverse-phase HPLC with electrochemical detection in 106 children (28 with NB (13 newly diagnosed), 25 with other solid tumors, 28 hospitalized for nonneoplastic diseases, and 25 healthy children). P-DOPAC or p-DOPA concentrations were above the upper normal range in 92% of untreated NB patients, as were u-HVA or u-VMA levels. None of these tumor markers was correlated to tumor stage or survival. P-DOPA but not p-DOPAC was correlated to age in NB children. Increased values of p-DOPAC and p-DOPA were found in one patient surviving NB for 10 years. Plasma DOPAC concentrations were decreased in children hospitalized for non-NB diseases, probably reflecting reduced food intake. Plasma analyses of DOPA and DOPAC seem to be useful alternatives in the diagnosis and follow-up of NB if urine sampling is to be avoided. Plasma DOPAC may be an index of nutritional status in various diseases.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1988

Equilibrium dialysis studies of plasma binding of thyroxine, triiodothyronine and their glucuronide and sulfate conjugates in human and cat plasma.

Binding of thyroxine (T4), triiodothyronine (T3) and their glucuronide and sulfate conjugates, T4G, T3G, T4S and T3S, was assessed by equilibrium dialysis in plasma from 6 euthyroid humans and 5 euthyroid cats. In humans, the dialyzable percentages of T4, T4G and T4S were 0.029 +/- 0.003 (mean +/- S.D.), 0.14 +/- 0.04 and 0.08 +/- 0.02 respectively. For T3, T3G and T3S they were 0.31 +/- 0.04, 0.33 +/- 0.07 and 0.22 +/- 0.02. In cats, the corresponding values for T4, T4G and T4S were 0.057 +/- 0.009, 0.20 +/- 0.10 and 0.53 +/- 0.04; for T3, T3G and T3S they were 0.47 +/- 0.08, 0.51 +/- 0.11, and 0.53 +/- 0.11. We conclude that glucuronide conjugation has little or no inhibiting effect on the plasma binding of T3, and that T3S is actually more tightly bound than T3 in human (but not feline) plasma. On the other hand, conjugation to either the glucuronide or the sulfate markedly reduced T4 binding in plasma from both species.

Adult↗

PubMed1974

HeLa cell plasma membranes. I. 5'-Nucleotidase and ouabain-sensitive ATPase as markers for plasma membranes.

A method for the preparation of HeLa cell plasma membrane ghosts is described. The purity of the plasma membrane fraction was examined by phase contrast and electron microscopy, by chemical analysis, and by assay of marker enzymes. Data on the composition of the plasma membrane fraction are given. It was observed that the distribution pattern of 5'-nucleotidase activity among the subcellular fractions differed from that of ouabain-sensitive ATPase. In addition, the specific activity of 5'-nucleotidase did not follow the distribution of the membrane ghosts. Thus, this enzyme would seem unsuitable as a plasma membrane marker. A complete balance sheet for marker enzyme activities during the fractionation is necessary for the calculation of increase in specific activity because the activities of both 5'-nucleotidase and ouabain-sensitive ATPase might change during the fractionation procedures.

Adenosine Triphosphatases↗

PubMed1979

Fate of plasma membrane during endocytosis. I. Uptake and processing of anti-plasma membrane and control immunoglobulins by cultured fibroblasts.

The uptake and processing by cultured rat embryo fibroblasts of control rabbit immunoglobulins (C IgG) or IgG directed against plasma membrane constituents (anti-PM IgG), and labeled with fluorescein (F) or with radioactive acetate (A), have been investigated by cell fractionation and immunological techniques. Both F and A anti-PM IgGs become bound to the cell surface, by a process that is slow, but largely temperature-independent. In the presence of an excess of high-affinity antibodies, binding reaches an absolute limit which corresponds to extensive coating of the plasma membrane. The anti-PM IgGs remain attached to the membrane for at least several days, even at 37 degrees C, with no significant transfer to lysosomes or degradation. In contrast, C IgGs are handled very differently by the fibroblasts, and their fate is strikingly affected by the type of labeling used. AC IgG is taken up slowly, at a rate proportional to its concentration, and is subsequently broken down in what appears to be lysosomes. Part of the AC IgG also binds to the plasma membrane. FC IgG is taken up many times faster than AC IgG, though with the same strict linearity as a function of concentration. Most of the FC IgG taken up is stored in cytoplasmic granules which behave like lysosomes. For reasons that are not understood, only about half of the stored FC IgG can be broken down. Cells exposed simulatnaously to AC IgG and FC IgG, or to A anti-PM IgG and FC IgG, handle each type of IgG in its characteristic fashion. Kinetic analysis of these results indicates that Ac IgG could be taken up by fluid endocytosis, but that FC IgG must be interiorized by a selective mechanism, presumably adsorptive in nature. That anti-PM antibodies remain stably bound to the plasma membrane and do not interfere with the uptake of FC IgG is interpreted to indicate either that two distinct membrane domains are involved in the two phenomena, or that membrane patches coated with anti-PM IgG participate in endocytosis, and are recycled back to the cell surface after delivering their contents intracellularly.

Animals↗

PubMed1976

Relationships between cigarette smoking, oral contraceptives, and plasma vitamins A, E, C, and plasma triglycerides and cholesterol.

Plasma vitamins A, E, and C, plasma triglycerides and cholesterol, and leukocyte vitamin C were examined in young healthy adult females who were cigarette and/or oral contraceptive users. It was found that cigarette smoking slightly increased the levels of vitamin A, triglycerides, and cholesterol while oral contraceptives significantly increased these plasma lipids. The effects of cigarette smoking and oral contraceptives on these substances were additive. Neither cigarette smoking nor oral contraceptives had any significant effect on plasma vitamins E and C. Oral contraceptives slightly decreased the level of leukocyte vitamin C in the cigarette smokers. Cigarette smoking did not impart and acute effect on these parameters.

Adult↗

PubMed2005

Determination of prednisolone and prednisone in plasma, whole blood, urine, and bound-to-plasma proteins by high-performance liquid chromatography.

A high-performance liquid chromatographic technique for the simultaneous determination of prednisolone and prednisone in human plasma, whole blood, urine, and bound-to-plasma proteins, using betamethasone as internal standard, is presented. Liquid-liquid extraction is used for whole blood samples, and solid phase extraction is used for plasma, urine, and proteins bound to plasma. The accuracy, precision, specificity, linearity, and repeatability meet the requirements of current recommendations in bioanalytical method validation. The method is suitable for high altitude pharmacokinetic studies, in which the quantitation of drugs in those fluids is required. The results from healthy volunteers are presented.

Blood Proteins↗

PubMed1998

Dietary pectin with high viscosity lowers plasma and liver cholesterol concentration and plasma cholesteryl ester transfer protein activity in hamsters.

We fed semipurified diets containing pectin with either a high or low in vitro viscosity at a level of 3 g/100 g air-dried diet to hamsters for 8 wk. A control group was fed cellulose and a positive control group was fed psyllium. The pectins used were a calcium-sensitive pectin (CS-pectin) that has a high viscosity and a noncalcium-sensitive pectin (NCS-pectin) that has a low viscosity. In the presence of calcium, CS-pectin has a more than 80-fold higher viscosity than NCS-pectin which offered the opportunity to investigate the possible role of viscosity in the hypolipidemic properties of pectin. The hamsters fed CS-pectin or psyllium had considerably lower plasma cholesterol concentrations (3.69 +/- 0.44 and 4.21 +/- 0.45 mmol/L, respectively, mean +/- SD, n = 14) than those fed NCS-pectin (5.03 +/- 1.15 mmol/L) or cellulose (5.72 +/- 1. 04 mmol/L). Differences in total plasma cholesterol were reflected in both high density lipoprotein and very low density lipoprotein cholesterol. There was no effect of fiber on low density lipoprotein cholesterol levels. Liver cholesterol concentrations paralleled the plasma cholesterol levels and were 9.91 +/- 2.48 micromol/g of liver for the CS-pectin group, 15.03 +/- 5.75 for the psyllium group, 17. 69 +/- 10.66 for the NCS-pectin group, and 25.57 +/- 9.23 for the cellulose group. Fecal bile acid and neutral steroid excretion tended to be higher in the hamsters fed CS-pectin than in their counterparts fed NCS-pectin. The hamsters fed psyllium had significantly greater fecal excretions of bile acids than the hamsters fed cellulose, CS-pectin or NCS-pectin, whereas the excretion of fecal neutral sterols tended to be lower. Plasma cholesteryl ester transfer protein activity was significantly lower in the hamsters fed CS-pectin than in those fed NCS-pectin. The results of this study suggest that the viscosity of pectins may determine their cholesterolemic effect.

Animals↗

PubMed2000

Dietary restriction of single essential amino acids reduces plasma insulin-like growth factor-I (IGF-I) but does not affect plasma IGF-binding protein-1 in rats.

The effects of dietary restriction of a single essential amino acid (EAA) on insulin-like growth factor-I (IGF-I) and IGF-binding protein (IGFBP)-1 were investigated in rats. Rats were fed experimental diets containing amino acid (AA) mixtures in which the concentrations of all EAA were at levels recommended by the National Research Council (control), in which a single EAA was restricted to 20% of that of the control diets (Leu(-), Lys(-), Met(-) or Thr(-)), or in which the diet was devoid of amino acids (AA(-)). To eliminate the effect of differences in energy intake, rats were fed the mean amount of food as consumed by the AA(-) group on the previous day. Growth was significantly retarded in rats fed diets restricted in just one EAA compared with that of rats fed the control diet, and further growth retardation was observed in rats fed the AA(-) diet. On the other hand, the plasma IGF-I concentrations in the groups with a single EAA restriction or in the AA(-) group were 66% (P: < 0. 05) and 50% (P: < 0.05) of that of the control group, respectively. The effect of any single EAA restriction was not significantly different from that of total AA deprivation. The plasma IGFBP-1 concentration in the control group did not differ from that of rats fed diets with the single EAA restrictions except for methionine restriction, but it was approximately 6-fold greater in the AA(-) group. Differences in plasma IGFBP-1 concentration under these conditions could be explained by differences in hepatic IGFBP-1 mRNA contents. Based on these results, we conclude that restriction of single EAA does not affect IGFBP-1 synthesis in vivo, although the deprivation of a single EAA has been reported to increase IGFBP-1 production in hepatocyte cultures. Our results also indicated that a single EAA restriction decreased IGF-I production but did not affect IGFBP-1 production. The present study suggests that not only plasma IGF-I, but also IGFBP-1, affects the magnitude of growth retardation in vivo.

Amino Acids, Essential↗

PubMed2000

Carotenoid bioavailability in humans from tomatoes processed in different ways determined from the carotenoid response in the triglyceride-rich lipoprotein fraction of plasma after a single consumption and in plasma after four days of consumption.

Tomatoes are the main dietary source of lycopene, and the bioavailability of lycopene from tomato paste is higher than that from fresh tomatoes. We investigated systematically the effect of mechanical homogenization and heating on the bioavailability of carotenoids from canned tomatoes. Further, we compared the carotenoid response in triglyceride-rich lipoproteins (TRL) after single consumption with the change in fasting plasma carotenoid concentrations after 4 d of daily consumption. In a split plot design, 17 men and women consumed tomatoes which had received minimal additional heating and 16 others consumed extensively additionally heated tomatoes (1 h at 100 degrees C). These tomatoes were not, mildly or severely homogenized. The tomato products were consumed daily (ca. 22 mg/d lycopene) for 4 d. Eleven participants provided postprandial blood samples on the d 1 and all gave fasting blood samples on d 1 and 4. Homogenization enhanced the lycopene response significantly (P<0.05) both in TRL [mean areas under the curves: 54.9, 72.0 and 88.7 nmol. h/L (SE 11.0) for not, mildly and severely homogenized tomatoes, respectively] and in plasma [mean changes: 0.19, 0.22 and 0.23 micromol/L (SE 0.009), respectively]. Additional heating also tended to enhance the lycopene responses in TRL (P = 0.14) and plasma (P = 0.17). Similar effects to those for lycopene were found for beta-carotene. We conclude that the intactness of the cellular matrix of tomatoes determines the bioavailability of carotenoids and that matrix disruption by mechanical homogenization and/or heat treatment enhances the bioavailability. The carotenoid response in plasma after 4 d intervention can be used to compare the bioavailability of carotenoids from different foods.

Adult↗

PubMed2002

Selenium deficiency in Fisher-344 rats decreases plasma and tissue homocysteine concentrations and alters plasma homocysteine and cysteine redox status.

The purpose of the present study was to determine the effect of graded amounts of dietary selenium on plasma and tissue parameters of methionine metabolism including homocysteine. Male weanling Fisher-344 rats (n = 7-8/group) were fed a selenium-deficient, torula yeast-based diet, supplemented with 0 (selenium deficient), 0.02, 0.05 or 0.1 microg (adequate) selenium (as selenite)/g diet. After 61 d, plasma total homocysteine and cysteine were decreased (P < 0.0001) and glutathione increased (P < 0.0001) by selenium deficiency. The concentrations of homocysteine in kidney and heart were decreased (P = 0.02) by selenium deficiency. The activities of liver betaine homocysteine methyltransferase, methionine synthase, S-adenosylmethionine synthase, cystathionine synthase and cystathionase were determined; selenium deficiency affected only betaine homocysteine methyltransferase, which was decreased (P < 0.0001). The ratios of plasma free reduced homocysteine (or cysteine) to free oxidized homocysteine (or cysteine) or to total homocysteine (or cysteine) were increased by selenium deficiency, suggesting that selenium status affects the normally tightly controlled redox status of these thiols. Most differences due to dietary selenium were between rats fed 0 or 0.02 microg selenium/g diet and those fed 0.05 or 0.1 microg selenium/g diet. The metabolic consequences of a marked decrease in plasma homocysteine and smaller but significant decreases in tissue homocysteine are not known.

Animals↗

PubMed1985

Comparison of glycosylated hemoglobin and fasting plasma glucose with two-hour post-load plasma glucose in the detection of diabetes mellitus.

In the course of a screening for diabetes mellitus in the Hôtel-Dieu Hospital in Paris, from September 15, 1981 to April 1, 1984, an oral glucose tolerance test and a measurement of glycosylated hemoglobin were performed on 333 outpatients. With two-hour plasma glucose as a reference, the sensitivities of glycosylated hemoglobin, fasting plasma glucose, and a combination of glycosylated hemoglobin and fasting plasma glucose equal, respectively, 60.0%, 52.0%, and 40.0%; the specificities 90.9%, 98.7%, and 99.4%; the predictive value for a positive diagnosis 34.9%, 76.5%, and 83.3%. If one takes into account the implications of diabetes mellitus, especially its economic and psychosociologic consequences, it seems better for diagnosis--from a public health point of view--to use tests with a high degree of specificity and a high predictive value for a positive diagnosis, such as the combination of fasting plasma glucose and glycosylated hemoglobin, than tests with a good sensitivity but poor specificity. In the long term, validation of glycosylated hemoglobin as a diagnostic test for asymptomatic diabetes mellitus will be obtained only by reference to unquestionable criteria of the disease, determined by longitudinal survey.

Adolescent↗

PubMed1990

Bovine plasma protein C inhibitor with structural and functional homologous properties to human plasma protein C inhibitor.

Bovine plasma protein C inhibitor was purified; it was then characterized in comparison with human protein C inhibitor. The specific inhibitory activity of the purified inhibitor for bovine activated protein C was 8,500 times that of the inhibitor in plasma. The purified inhibitor showed a single band with Mr 56,000 by SDS-PAGE at pH 7.0, and two bands at pH 8.8, a major one with Mr 56,000 and a minor one with Mr 105,000, under both unreduced and reduced conditions. The pI range of the inhibitor was between 4.4 and 6.1. The Mr of the inhibitor was reduced by treatment with neuraminidase, O-glycanase, and also with glycopeptidase-A, suggesting that the inhibitor has both Asn-linked and Ser/Thr-linked carbohydrate chains. Twenty-seven of the NH2-terminal 49 amino acid residues of the bovine inhibitor, which lacks the first 4 residues from the NH2-terminal amino acid sequence of human inhibitor, were identical to those of the human inhibitor. The bovine inhibitor inhibited bovine and human activated protein C, human thrombin, Factor Xa, Factor XIa, and plasma kallikrein with Ki = 1.0, 5.2, 2.6, 3.0, 1.3 X 10(-8) M, and 4.5 X 10(-9) M, respectively. The inhibitory rates for activated protein C and thrombin were accelerated significantly in the presence of heparin or negatively charged dextran sulfate. However, the acceleration by heparin or dextran sulfate for the inhibition of Factor Xa, Factor XIa, and plasma kallikrein was not significant. The bovine inhibitor did not inhibit human Factor XIIa or plasmin.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗