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PubMed1998

Variability of the metabolic effect of soluble insulin and the rapid-acting insulin analog insulin aspart.

OBJECTIVE: To study the intra- and interindividual variability of the metabolic activity of soluble insulin and of the rapid-acting insulin analog insulin aspart after subcutaneous injection. RESEARCH DESIGN AND METHODS: A total of nine healthy male volunteers received subcutaneous injections of soluble insulin (0.2 U/kg) in the abdominal region on each of the four study days. Another 10 volunteers received an injection of insulin aspart four times. Glucose infusion rates necessary to neutralize the blood glucose-lowering effect of the administered insulin were registered during euglycemic glucose clamps (blood glucose 5.0 mmol/l; basal intravenous insulin infusion 0.15 mU x kg(-1) x min(-1) over the subsequent 600 min. We investigated the variation in metabolic activity by calculating coefficients of variation (CVs). RESULTS: In comparison to soluble insulin, subcutaneous injections of insulin aspart led to a more rapid onset of action and a shorter duration of action. Subcutaneous injection of the insulin preparations resulted in intraindividual CVs of the summary measures between 10 and 30% (soluble insulin vs. insulin aspart: maximal metabolic activity 15+/-7 vs. 16+/-10%, time to maximal metabolic activity 14+/-10 vs. 11+/-6%; NS between the preparations [means +/- SD]). The decline to half-maximal activity after maximal activity showed a lower intraindividual CV with insulin aspart (19+/-9 vs. 11+/-5%; P = 0.018). The interindividual CVs were higher than the intraindividual CVs (26 vs. 28, 23 vs. 19, and 26 vs. 17%). Generally, the pharmacodynamic variability was higher than the pharmacokinetic variability. For the pharmacokinetic measures, the intra- and interindividual variability in t(max) was lower for insulin aspart than for soluble insulin. CONCLUSIONS: The metabolic effect of soluble insulin shows an intraindividual variability of 10-20% in healthy volunteers, even under strictly controlled experimental conditions. The overall variability of action of insulin aspart was comparable to that of soluble insulin.

Adult↗

PubMed1996

Effect of maturity on digestion kinetics of water-soluble and water-insoluble fractions of alfalfa and brome hay.

Alfalfa and bromegrass, each harvested at five different stages of maturity, were separated into water-insoluble and -soluble fractions. The NDF concentrations ranged from 19 to 43% for alfalfa and from 42 to 58% for brome. The rates of digestion, by mixed ruminal microflora, of the unfractionated forage and of the water-insoluble and -soluble fractions were measured in vitro using pressure sensors to monitor gas production. Both forages showed the expected decline in fiber digestibility with increasing maturity. A dual-pool logistic model gave pool sizes, specific rates, and a single lag time for both the faster- and slower-digesting fractions. The main difference between alfalfa and brome was in the soluble pool. This pool produced approximately 40% of the total gas in alfalfa, 25% in brome. The specific digestion rates of the brome soluble pool were approximately 50% higher than those for alfalfa. Net VFA production showed a somewhat higher acetate: propionate ratio for brome (3.2) compared with alfalfa (2.2), but there was little change with increasing maturity within a given forage. Gas production curves for the unfractionated forage showed a 0 to 10% positive deviation from curves created by adding data from separate digestion of the insoluble and soluble forage fractions. Gas measurements offer a promising approach to the study of the water-soluble extracts of forages and the interaction of the soluble- and insoluble-fractions during fermentation.

Acetates↗

PubMed2002

Apparent ruminal degradation and rumen escape of soluble nitrogen fractions in grass and grass silage administered intraruminally to lactating dairy cows.

The main objective of this study was to investigate in vivo ruminal degradation and rumen escape of soluble N fractions in grass and grass silage. Soluble protein and long-chain peptides (PLP), small peptides (SP) and free AA (FAA) were obtained from fresh grass and grass silages fertilized with different levels of N. Soluble extracts from the forages were pulse dosed into the rumen of three cannulated lactating dairy cows, and a simple or complex model was used to examine the kinetics of the soluble N fractions in the rumen. When soluble extracts from silage were investigated, pulse dosages of total nonammonia N (NAN) were 21, 27, and 32 g, while for fresh grass only dosages of 20 g were ruminally administered. In the silage extracts, mean proportions of PLP-N, SP-N, and FAA-N in the NAN were 30, 52, and 18%, respectively, whereas in the fresh grass the corresponding values were 67, 20, and 13%. From silage extracts, all three soluble N fractions showed a linear decrease (P < 0.05) in degradation rate and an increase (P < 0.05) in ruminal escape with increasing dosage. In silage, mean degradation rates, parameterized from the complex model, were 230, 214, and 334%/h for PLP-N, SP-N, and FAA-N, respectively, and the ruminal escape was highest (P < 0.05) for SP-N (11.2% of dose) and lowest (P < 0.05) for FAA-N (5.0% of dose). No differences in degradation rate and ruminal escape between fresh grass and silage were observed. However, the proportion of N dose converted to ammonia was only 24% in the fresh grass, whereas for the silages a mean value of 76% was found. From this study, it is concluded that a significant amount of dietary soluble N escapes ruminal degradation, and thus contributes to the intestinal AA supply. Moreover, if the main aim is to study degradation kinetics of individual N fractions, a complex model should be used in the evaluation. This model can also be used to study ruminal synchronization of N and energy for microbial growth.

Animal Feed↗

PubMed2004

Growth performance of nursery pigs fed diets containing increasing levels of corn distiller's dried grains with solubles originating from a modern Midwestern ethanol plant.

Two experiments were conducted to determine the effects of including distiller's dried grains with solubles in nursery diets on growth performance, and to establish maximum inclusion rates for corn distiller's dried grains with solubles originating from modern, "new-generation" ethanol plants (built since 1990). Ninety-six crossbred pigs (BW = 6.18 +/- 0.14 kg) were blocked by gender and ancestry, and pigs within each block were randomly assigned to one of six dietary treatments (four pigs/pen, four pens/dietary treatment) in each of two growth performance experiments. Dietary treatments provided 0, 5, 10, 15, 20, or 25% distiller's dried grains with solubles during Phases 2 and 3 of a three-phase nursery feeding program for early-weaned pigs. Pigs in Exp. 1 were slightly older (19.0 vs. 16.9 d of age) and heavier (7.10 vs. 5.26 kg) at the beginning of the experiment compared to pigs in Exp. 2. All pigs in both experiments were provided a commercial pelleted Phase 1 diet for the first 4 d after weaning and were then switched to their respective experimental Phase 2 diets, which were fed for 14 d, followed by their respective Phase 3 experimental diets, which were fed for a subsequent 21-d feeding period. Experimental diets were formulated to contain equivalent apparent ileal digestible lysine (1.35 and 1.15%), apparent ileal digestible methionine + cystine (0.80 and 0.65%), ME (3,340 and 3,390 kcal/kg), calcium (0.95 and 0.80%), and total phosphorus (0.80 and 0.70%) within Phases 2 and 3, respectively. Overall growth rate, ending body weight, and feed conversion were similar among pigs regardless of dietary distiller's dried grains with solubles level for both experiments. In Exp. 1, feed intake was not affected by dietary treatment (P > 0.10). In Exp. 2, however, increasing the level of distiller's dried grains with solubles linearly decreased feed intake (P < 0.02) during Phase 2 and tended to decrease voluntary feed intake (P < 0.09) over the length of the experiment. These results suggest that the corn distiller's dried grains with solubles used in this study can be included in Phase 3 diets for nursery pigs at dietary levels of up to 25% without negatively affecting growth performance after a 2-wk acclimation period. Including high levels of corn distiller's dried grains with solubles in diets for pigs weighing less than 7 kg in BW, however, may negatively influence feed intake and growth.

Aging↗

PubMed1996

Solubility and intrinsic dissolution rate of alprazolam crystal modifications.

The purpose of the study was to determine the solubility and the intrinsic rates of dissolution of three crystal modifications, two anhydrate, and one dihydrate of alprazolam, a 1,4-benzodiazepine derivative. Solubility was determined by ultraviolet spectrophotometry at different levels of pH, and intrinsic dissolution rates were determined by a rotating disk method. The apparent solubility of alprazolam crystal modifications was dependent on pH, being 8-10 mg/ml at pH 1.6 and 0.1 mg/ml at pH 5.0. The apparent solubility values for the anhydrate forms were similar, whereas the hydrate form showed lower apparent solubility at each pH. The mean intrinsic rates of dissolution for the anhydrate forms were 16 and 18 micrograms cm-2 min-1, and for the dihydrate modification 21 micrograms cm-2 min-1 at 50 rpm, respectively. At 75 rpm, the corresponding values were 22, 22, and 27 micrograms cm-2 min-1. The rate of intrinsic dissolution was also dependent on the pH. It can be concluded that the apparent solubility and the intrinsic dissolution rate of the anhydrate and hydrate forms were different. The obtained apparent solubility values at different levels of pH for the water-solvated crystal modification were evidently lower than those of the two anhydrate forms studied. Furthermore, the intrinsic rate of dissolution was significantly (p < 0.05) higher for the hydrate form of alprazolam.

Alprazolam↗

PubMed1985

Varying protein content and nitrogen solubility for pluriparous, lactating Holstein cows: lactation performance and profitability.

Effects on total lactation performance of varying ration crude protein (15.3 vs. 13.6% of dry matter) and nitrogen solubility (35 vs. 45% of total nitrogen) in early lactation was studied using 57 pluriparous Holstein cows. Grain was fed according to production so as to minimize change in body weight throughout lactation. Forages high in nitrogen solubility, corn and grass silages, were fed free-choice. Percent concentrate in ration dry matter was highest (64%) 5 to 8 wk postpartum and lowest (3%) 33 to 44 wk postpartum. Protein and nitrogen solubility were varied by formulating four protein supplements fed as 10% of the grain allocation, so differences in treatments applied narrowed as lactation progressed. Cows fed the medium-protein diets produced 196 kg more milk than those receiving low-protein diets, but their peak daily milk yield was only .6 kg higher. Cows receiving rations with reduced nitrogen solubility produced 347 kg more milk than those fed the higher solubility diets, but their peak daily milk yield was 1.0 kg lower. Income above fed cost for the lactation was highest and postpartum loss in body weight was least for cows receiving medium-protein and low-solubility rations in early lactation, but no differences were significant. Both milk yield (38.3 to 40.6 kg) and total dry matter intake (3.74 to 3.91% body weight) means were maximum 6 to 7 wk postpartum, but lactation performance was not proportional to peak milk yield. When cows are fed to minimize body fat mobilization, response to increased protein in the diet is small. Reducing nitrogen solubility of silage-based diets increased milk produced per unit grain fed. There were no adverse effects of treatments on breeding efficiency or herd health.

Animals↗

PubMed1998

Proteolysis during ensilage of forages varying in soluble sugar content.

The effect of contrasting concentrations of water-soluble carbohydrates of herbage on silage fermentation and composition was examined using grass with high [250 g/kg of dry matter (DM)] concentrations of water-soluble carbohydrates and grass and clover with low (66 g/kg of DM) concentrations of water-soluble carbohydrates. Herbages were ensiled untreated, after inoculation with lactic acid bacteria, or after treatment with formic acid. Good quality silages were produced from herbage with high concentrations of water-soluble carbohydrates, regardless of treatment, and all pH values were below 3.7 after 90 d of ensilage. However, the silage formed from inoculated herbage had a significantly lower concentration of ammonia N and a significantly higher proportion of residual ribulose-1,5-bisphosphate carboxylase compared with the other two silages. Fast protein liquid chromatography (Pharmacia, Uppsala, Sweden) was used to measure ribulose-1,5-bisphosphate carboxylase, and measurement of true plant protein fractions in herbage and silage showed benefits over traditional measurements such as the measurement of N and ammonia N. Herbages with low concentrations of water-soluble carbohydrates produced inferior quality silages that had lower ribulose-1,5-bisphosphate carboxylase contents and higher ammonia N contents, regardless of treatment; few significant differences were observed among treatments. Under good ensiling conditions, when available water-soluble carbohydrate is adequate, the use of inoculants can improve fermentation characteristics and increase the ribulose-1,5-bisphosphate carboxylase content of silages. However, when the herbage has low concentrations of water-soluble carbohydrates, even in inoculated herbages, lactic acid bacteria may follow a heterofermentative pathway instead of a homofermentative pathway, which can result in a decrease in silage quality and a reduction in intact ribulose-1,5-bisphosphate carboxylase.

Ammonia↗

PubMed2002

Rise in serum soluble intercellular adhesion molecule-1 levels with vasospasm following aneurysmal subarachnoid hemorrhage.

OBJECT: Proinflammatory adhesion molecule expression has been demonstrated to be elevated in patients with aneurysmal subarachnoid hemorrhage (SAH). Recent studies have shown that elevations in soluble intercellular adhesion molecule-1 (ICAM-1) may be predictive of poor outcome in patients with good grade (Hunt and Hess Grades 1-2) aneurysmal SAH at delayed time points that correspond with the risk period for cerebral vasospasm. In addition, ICAM-1 is upregulated in experimental models of vasospasm. Unfortunately, the relationship of adhesion molecule expression to human vasospasm remains unclear. The authors hypothesized that the delayed elevation of soluble ICAM-1 in patients with aneurysmal SAH is associated with the development of cerebral vasospasm. METHODS: Eighty-nine patients with aneurysmal SAH were prospectively enrolled in a study and stratified according to the presence or absence of vasospasm, as evidenced by daily monitoring of transcranial Doppler (TCD) velocities (presence, > 200 cm/second; absence, < 120 cm/second). Levels of soluble ICAM-1 were determined using enzyme-linked immunosorbent assay every other day for 12 days post-SAH. An analysis of covariance model was used to evaluate trends in soluble ICAM-1 levels from 2 days prior to 6 days after the occurrence of documented vasospasm. Two groups of patients, matched for admission admission Hunt and Hess grade, were compared: nine patients with TCD velocities greater than 200 cm/second and nine patients with TCD velocities less than 120 cm/second. From among the patients with TCD velocities greater than 200 cm/second six patients with angiographically documented vasospasm were selected. Patients with TCD velocities less than 120 cm/second and matched admission Hunt and Hess grades but without angiographically documented vasospasm were selected. Patients with TCD-demonstrated vasospasm showed a significant mean rate of rise (p < 0.01) in soluble ICAM-1 levels during the perivasospasm period, but admission Hunt and Hess grade-matched control patients did not (p = not significant [NS]). There was a significant difference between these groups' rates of soluble ICAM increase (p < 0.01). Patients with both TCD- and angiographically demonstrated vasospasm likewise showed a highly significant mean rate of increase in soluble ICAM-1 levels during the perivasospasm period (p < 0.01), whereas admission Hunt and Hess grade-matched controls did not (p = NS). The difference beween these groups' rates of increase was highly significant (p < 0.001). CONCLUSIONS: These data suggest a role for ICAM-1 in the pathophysiology of cerebral vasospasm or its ischemic sequelae. As this relationship is further elucidated, adhesion molecules such as ICAM-1 may provide novel therapeutic targets in the prevention of vasospasm or its ischemic consequences.

Adult↗

PubMed2000

Effect of cyclodextrins on the solubility and stability of a novel soft corticosteroid, loteprednol etabonate.

To increase the aqueous solubility and stability of the soft corticosteroid loteprednol etabonate (LE), drug complexation using various cyclodextrins (CDs), such as gamma-cyclodextrin (gamma-CD), 2-hydroxypropyl-beta-cyclodextrin (HPBCD), maltosyl-beta-cyclodextrin (MBCD), mixture of glucosyl/maltosyl-alpha-, beta-, and gamma-cyclodextrin (GMCD), and heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DMCD), were attempted. The solubilizing and stabilizing effects of CD by itself or combined with various co-solvents were also investigated. Micronized (5 micron) LE was mixed in various aqueous CD or CD with cosolvent solutions. After equilibration and filtration at 23 degrees C, the solubility of LE was determined by HPLC. Subsequently, the stability of LE in the solutions was also determined by following the LE concentration change in the solution for an appropriate period. CD complexation significantly increased the aqueous solubility and stability of LE. The increase in solubility displayed a concentration dependency on CDs (0-50%). Among the five CDs used, DMCD showed the highest effects on the solubility (4.2-18.3 mg/ml in 10-50% DMCD) and stability (t90 > 4 years at 4 degrees C, when LE 0.5 mg/ml was dissolved in 10% DMCD solution) of LE. By adding co-solvents, such as glycerol, propylene glycol (PG), polyvinyl alcohol (PVA), and polyvinylpyrrolidone (PVP-10), the solubility of LE in DMCD solutions was further increased. Degradation of LE to the corresponding metabolites, delta 1-cortienic acid etabonate (AE) and delta 1-cortienic acid (A), in aqueous CD solutions appeared to be a predicted, two-step kinetics. Differential Scanning Calorimetry (DSC) was used to assist explaining the solubilizing and stabilizing activity differences between CDs. LE/CD mixture or lyophilized LE/CD complex was scanned at a rate of 20 degrees C/min. The exothermic peak found in the DSC diagram with LE/DMCD sample, but not with LE/HPBCD samples, suggests a stronger complex formed between LE and DMCD, resulting in higher solubility and stability of LE in DMCD than in HPBCD.

Androstadienes↗

PubMed2000

Plasma soluble adhesion molecules and endothelium-dependent vasodilation in early human atherosclerosis.

Levels of soluble cellular adhesion molecules are increased in patients with atherosclerosis, and have been found to predict coronary heart disease. Therefore these molecules have been suggested to represent laboratory markers for inflammation and activation of endothelial cells. Impaired endothelium-dependent vasodilation has been demonstrated to be an early marker of atherosclerosis. We hypothesized that soluble adhesion molecules are related to impaired endothelium-dependent vasodilation and may serve as an early marker of atherosclerosis. Patients (n=52) with moderate and uncomplicated hypercholesterolaemia [low-density lipoprotein (LDL)-cholesterol 4.89+/-1.26 mmol/l] were compared with healthy controls (n=43; LDL-cholesterol 2.44+/-0.79 mmol/l). Endothelium-dependent vasodilation of the forearm vasculature was assessed by intra-arterial infusion of acetylcholine (12 and 48 microg/min). Forearm blood flow was measured by venous occlusion plethysmography. Plasma concentrations of the soluble forms of ICAM-1 (intercellular cell adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1) and E-selectin were measured by ELISA. Hypercholesterolaemic patients had impaired endothelium-dependent vasodilation in comparison with healthy controls (forearm blood flow after 48 microg/min acetylcholine: 21.3+/-10.6 and 30.4+/-16.3 ml. min(-1).100 ml(-1) respectively; P=0.002). Plasma concentrations of soluble adhesion molecules were not different between hypercholesterolaemic patients and controls (ICAM-1, 196+/-56 and 180+/-38 ng/ml respectively; VCAM-1, 431+/-137 and 405+/-65 ng/ml respectively; E-selectin, 39+/-17 and 37+/-12 ng/ml respectively). Moreover, levels of soluble adhesion molecules were not correlated with endothelium-dependent vasodilation. Thus, in hypercholesterolaemic patients without clinical atherosclerosis, levels of soluble adhesion molecules were not elevated in comparison with healthy controls. In addition, these markers of endothelial inflammation were not related to impaired endothelium-dependent vasodilation. Our data indicate that measurement of levels of soluble adhesion molecules cannot replace assessment of endothelium-dependent vasodilation in detection of early hypercholesterolaemic atherosclerosis.

Adolescent↗

PubMed1975

The role of granulocytes in the activation of intravascular coagulation and the precipitation of soluble fibrin by endotoxin.

This study examines the role of neutrophils (PMN) in the pathogenesis of endotoxin-induced microclot formation. It is intended to clarify whether granulocytes are involved in endotoxin-induced activation of intravascular coagulation (generation of soluble fibrin) and/or in endotoxin-induced precipitation of soluble fibrin. Precipitation of soluble fibrin was achieved by injection of endotoxin into ancrod-infused rabbits with circulating soluble fibrin (first model). Activation of intravascular coagulation was elicited by two intravenous injections of endotoxin into rabbits (second model). Seventy-two and ninety-six hours after injection of nitrogen mustard, leukopenic rabbits had PMN counts between 0 and 50 cells per mul. Neutropenia did not prevent the occurrence of glomerular microclots after infusion of ancrod and injection of endotoxin (first model). Neutropenia influenced neither the decrease in mean fibrinogen concentrations nor the drop in mean platelet counts after ancrod and endotoxin administration. In contrast to the first model, neutropenia prevented the occurrence of glomerular microclots and of circulating soluble fibrin after two injections of endotoxin (second model). It did not, however, protect rabbits from the decrease in mean platelet counts after endotoxin administration. These data indicate that granulocytes are involved in endotoxin-induced activation of intravascular coagulation and the production of soluble fibrin but are not essential to endotoxin-induced precipitation of soluble fibrin.

Animals↗

PubMed2001

Cd, Cu, Pb, and Zn coprecipitates in Fe oxide formed at different pH: aging effects on metal solubility and extractability by citrate.

Coprecipitates of heavy metals with Fe oxides may form in contaminated soil, water, and sediment systems, particularly when oxidation-reduction processes are occurring. Once formed, coprecipitates with ferrihydrite could limit heavy metal mobility, solubility, toxicity, and bioavailability in geochemical systems. In this study, Cd, Cu, Pb, and Zn were coprecipitated with Fe by titration to pHs 6 and 7. Metal solubility was monitored during the coprecipitation process to pH 7 and after aging of the product. In the coprecipitate formed at pH 6, metal solubility was determined after the system reached pH 6 and at subsequent time intervals. We also reacted the coprecipitates with citrate and evaluated potential metal availability at increased aging times. The pH of coprecipitate formation had little effect on the long-term solubility of Cu and Zn, whereas soluble Cd was greater in the coprecipitate formed at pH 6. Soluble percentages of metals were low at both pH 6 and 7 for Cu and Pb but averaged 1.5 to 3% for Zn and greater than 40% for Cd. Hysteresis was observed in the coprecipitation curves for Zn and Cd, revealing reduced solubility after adsorption or coprecipitation. Lead and Cu failed to show hysteresis, with strong retention in the solid phase at pH greater than 6. The citrate-extractable fraction was greatest for Cd and Zn, less for Cu, and least for Pb. Citrate-extractable metal was higher for the coprecipitate formed at pH 7 than at pH 6, suggesting increased potential availability from coprecipitates formed at higher pH.

Citrates↗

PubMed2001

The effect of change in pH on the solubility of iron bis-glycinate chelate and other iron compounds.

The effect of a pH change from 2 to 6 was tested on the solubility of ferrous sulfate, ferrous fumarate, iron bis-glycine chelate (Ferrochel) and sodium-iron ethylenediaminetetraacetic acid (NaFeEDTA). It was found that at pH 2 ferrous sulfate, Ferrochel and NaFeEDTA were completely soluble and only 75% of iron from ferrous fumarate was soluble. When pH was raised to 6, iron from amino acid chelate and NaFeEDTA remained completely soluble while solubility from ferrous sulfate and ferrous fumarate decreased 64 and 74%, respectively compared to the amount of iron initially soluble at pH 2. These results suggest that iron solubility from iron bis-glycine chelate and NaFeEDTA is not affected by pH changes within the ranges tested, probably because iron remained associated to the respective compounds.

Edetic Acid↗

PubMed2001

Effect of water-soluble polymers on naproxen complexation with natural and chemically modified beta-cyclodextrins.

The combined effect of cyclodextrins (CDs) (beta-, methyl-beta-, hydroxypropyl-beta-cyclodextrins) and water-soluble polymers (sodium carboxymethylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone K30, polyethylene glycol 6000) on naproxen solubility improvement was studied. Phase solubility analysis at 25 degrees C was used to investigate the interaction of the drug with each cyclodextrin (or polymer, alone or in the presence of the different water-soluble polymers (or cyclodextrins). The combined use of polymer and cyclodextrin was always clearly more effective in enhancing the aqueous solubility of naproxen in comparison with the corresponding drug-polymer or drug-cyclodextrin binary systems, and the solubilization enhancement was not simply additive, but synergistic. Water-soluble polymers increased the complexation efficacy of cyclodextrins toward naproxen (as shown by the increased stability constants of the complexes), which resulted in enhanced drug solubility. No previous sonication or heating treatments of the drug-cyclodextrin-polymer suspensions was necessary to obtain this favorable effect. The best results were obtained in ternary systems with beta-cyclodextrin, which had a solubilizing effect toward naproxen in the presence of 0.25% w/v of the different hydrophilic polymers examined that was improved from 25% to about 80%, depending on the type of polymer.

Cyclodextrins↗

PubMed2003

Measurement of soluble fibrin monomer-fibrinogen complex in plasmas derived from patients with various underlying clinical situations.

We previously reported a monoclonal antibody named IF-43 that specifically recognizes thrombin-modified fibrinogen (desAA- and desAABB- fibrin monomer) bound with fibrinogen or other D(1) domain-containing plasmic fragments such as fragments X,Y, and D(1), but not intact fibrinogen or cross-linked fibrin degradation products (XDP). Here, we tentatively named such complexes, soluble fibrin monomer (FM) -fibrinogen complex. By utilizing IF-43, we have developed a kit to measure soluble FM-fibrinogen complex and compared the profiles with those of two established molecular markers for thrombo-embolic disorders: i.e. the thrombin-antithrombin complex (TAT) and the D-dimer in plasma of patients who underwent surgery without any thrombo-embolic complications. The result indicated that soluble FM-fibrinogen complex is a distinct entity from the two established molecular markers. We have also attempted to observe their profiles in patients with the disseminated intravascular coagulation syndrome (DIC). Although the pro-files of soluble FM-fibrinogen complex in individual patients appeared to vary from one patient to the other, the plasma level of soluble FM-fibrinogen complex was found to be increased at the initial phase of disseminated intravascular coagulation syndrome. Thus, the soluble FM-fibrinogen complex may serve as an independent molecular marker for the detection of thrombin generation and the diagnosis of thrombosis. The soluble FM-fibrinogen complex may also serve as a risk factor for thrombosis, because it may precipitate as insoluble complexes beyond its threshold in plasma, or when it is modified by thrombin.

Antithrombin III↗

PubMed1992

A soluble form of Fc gamma RIII is present in human serum and other body fluids and is elevated at sites of inflammation.

We have developed a highly sensitive and specific sandwich enzyme-linked immunosorbent assay (ELISA) to measure the concentration of Fc gamma RIII in serum and other body fluids. This ELISA is based on the use of monoclonal antibody (MoAb) (3G8) to Fc gamma RIII and a rabbit antiserum against Fc gamma RIII. The lower limit of detection of this ELISA was 1.5 nmol/L. The concentration of soluble Fc gamma RIII in normal serum ranged from 7.3 to 75.9 nmol/L. Soluble Fc gamma RIII was also present in other normal biologic fluids such as saliva, urine, and seminal fluid, but at much lower concentrations than that found in serum. Rabbit anti-Fc gamma RIII immunoblotted polypeptides immunoprecipitated with MoAb 3G8. Fc gamma RIII immunoprecipitated from a neutrophil lysate migrated from 40 to 76 Kd, whereas Fc gamma RIII immunoprecipitated from serum from the same donor migrated from 40 to 66 Kd. The soluble form of Fc gamma RIII apparently was bound to serum IgG, because immunoprecipitation of soluble Fc gamma RIII by MoAb 3G8 coprecipitated polypeptides that were identified by goat antihuman IgG. Incubation of neutrophils in vitro at 4 degrees C and 37 degrees C showed that Fc gamma RIII was released after 30 minutes of incubation at 37 degrees C. To determine whether there was a correlation between the concentration of soluble Fc gamma RIII in biologic fluids and inflammatory diseases, we measured the concentration of Fc gamma RIII in the bronchoalveolar lavage fluid from patients with adult respiratory distress syndrome (ARDS) and in the synovial fluid from patients with various forms of arthritis. In ARDS, we found concentrations of soluble Fc gamma RIII that were five to seven times higher than that found in the bronchoalveolar lavage fluids from healthy adults. The concentration of soluble Fc gamma RIII in the synovial fluid from patients with rheumatoid arthritis ranged from 10 nmol/L to 28 mumol/L. These results suggest that activated neutrophils, such as those at sites of inflammation, may release Fc gamma RIII.

Antigens, Differentiation↗

PubMed1992

[A comparative study of the in-vitro solubility and availability of magnesium from various sources for cattle].

Magnesium (Mg) is often added to the feed of cattle to meet the dietary requirements of this element. Magnesium oxide (MgO) is usually used. However, if the supplemented MgO does not dissolve in the rumen, it will not be effective. The solubility of eight preparations of MgO was measured with three different in vitro methods. Particle size and origin varied among the eight preparations. Solubility in vitro ranged from hardly soluble (MgO-C) to highly soluble (MgO-A). In an experiment with four cows with rumen fistulas (4 x 4), the solubility of the MgO preparations in vitro was found to parallel their solubility in the rumen and their urinary excretion. It was concluded that not only the amount of MgO added to the ration is important but also the solubility of the MgO.

Animal Feed↗

PubMed1990

Post soluble binding to the leukotriene D4 receptor from guinea pig lung membranes.

Guinea pig lung membranes were extracted with 1% digitonin and yielded a preparation that contained soluble leukotriene D4 (LTD4) receptor. Specific binding of the high affinity radiolabeled receptor antagonist [3H]ICI-198615 to the soluble LTD4 receptor was time dependent and reversible. The dissociation constant (Kd) and the density (Bmax) of [3H]ICI-198615 binding to the soluble LTD4 receptor was 0.2 +/- 0.08 nM and 380 +/- 40 fmol/mg of protein, respectively. Radioligand competition studies showed several classes of structurally diverse, functionally defined, receptor antagonists competed with [3H]ICI-198615 binding to the soluble receptor. The rank order of potency and specificity of these antagonists in binding to the soluble receptor were equivalent to those determined from the membrane-bound receptor binding assay and from the smooth muscle contraction assay. Binding of LTD4 to the soluble receptor was observed, in the competition assay, only in the low affinity state (Ki = 2 microM). Size-exclusion chromatography of the soluble LTD4 receptor showed that the apparent molecular weight of the LTD4 receptor in digitonin micelle was approximately 300,000.

Animals↗