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Biomedical subjects

D J Hoffman

Publications and source records attributed to D J Hoffman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Developmental toxicity of lead-contaminated sediment to mallard ducklings.

Sediment ingestion has been identified as an important exposure route for toxicants in waterfowl. The toxicity of lead-contaminated sediment from the Coeur d'Alene River Basin (CDARB) in Idaho was examined on posthatching development of mallard (Anas platyrhynchos) ducklings for 6 weeks. Day-old ducklings received either untreated control diet, clean sediment (24%) supplemented control diet, CDARB sediment (3,449 microg/g lead) supplemented diets at 12% or 24%, or a positive control diet containing lead acetate equivalent to that found in 24% CDARB. The 12% CDARB diet resulted in a geometric mean blood lead concentration of 1.41 ppm (WW) with over 90% depression of red blood cell ALAD activity and over threefold elevation of free erythrocyte protoporphyrin concentration. The 24% CDARB diet resulted in blood lead of 2.56 ppm with over sixfold elevation of protoporphyrin and lower brain weight. In this group the liver lead concentration was 7.92 ppm (WW), and there was a 40% increase in hepatic reduced glutathione concentration. The kidney lead concentration in this group was 7.97 ppm, and acid-fast inclusion bodies were present in the kidneys of four of nine ducklings. The lead acetate positive control group was more adversely affected in most respects than the 24% CDARB group. With a less optimal diet (mixture of two thirds corn and one third standard diet), CDARB sediment was more toxic; blood lead levels were higher, body growth and liver biochemistry (TBARS) were more affected, and prevalence of acid-fast inclusion bodies increased. Lead from CDARB sediment accumulated more readily in duckling blood and liver than reported in goslings, but at given concentrations was generally less toxic to ducklings. Many of these effects are similar to ones reported in wild mallards and geese within the CDARB.

Aminolevulinic Acid↗
PubMed2000

Mixed-function oxygenases, oxidative stress, and chromosomal damage measured in lesser scaup wintering on the Indiana Harbor Canal.

During the winter of 1993-1994, male lesser scaup (Aythya affinis) were collected on the heavily polluted Indiana Harbor Canal, East Chicago, Indiana, and examined for several bioindicators of chemical exposure. Livers were analyzed for activities of three cytochrome P450-associated monooxygenases and four measures of oxidative stress. Blood and spleen were analyzed by flow cytometry for chromosomal damage. In a concurrent study, scaup tissues were analyzed for organic and inorganic contaminants. Ethoxyresorufin-O-dealkylase (EROD) activity in livers of scaup collected in January 1994 was significantly higher than in livers of scaup collected in March 1994 or in livers of reference birds. Three hepatic monooxygenase activities were each significantly correlated with polycyclic aromatic hydrocarbon (PAH) concentrations in scaup carcasses. Thiobarbituric acid (TBA) activity in scaup livers was positively correlated with iron, boron, and lead concentrations in livers and polychlorinated biphenyl concentrations in carcasses. TBA activity was negatively correlated with protein-bound thiol activity and mercury concentrations in livers. The coefficient of variation of DNA content in scaup blood cells was correlated with PAH concentrations in scaup carcasses. This is the first field study with birds to demonstrate a correlation between liver monooxygenase activity and carcass PAH concentrations and to show a direct correlation between PAH concentrations in tissues and somatic chromosomal damage in blood.

Animals↗
PubMed2000

Why are nutritionally stunted children at increased risk of obesity? Studies of metabolic rate and fat oxidation in shantytown children from São Paulo, Brazil.

BACKGROUND: Previous research suggested that nutritionally stunted children may have increased risk of obesity, but little is known about potential underlying mechanisms. OBJECTIVE: We sought to test the hypothesis that stunted children have a low metabolic rate and impaired fat oxidation relative to nonstunted children. DESIGN: The subjects were 58 prepubertal boys and girls aged 8-11 y from the shantytowns of São Paulo, Brazil. Twenty-eight were stunted (height-for-age z score <-1.5) and 30 had similar weight-for-height but normal height (height-for-age z score >-1.5). Parents of children in the 2 groups had equivalent height and body mass index values. Fasting and postprandial energy expenditure, respiratory quotient (RQ), and substrate oxidation were measured with indirect calorimetry in a 3-d resident study in which all food was provided and body composition was measured with dual-energy X-ray absorptiometry. RESULTS: Stunted children had normal resting energy expenditure relative to body composition compared with control children (4559 +/- 90 and 4755 +/- 86 kJ/d, respectively; P: = 0.14) and had normal postprandial thermogenesis (2.4 +/- 0.3% and 2.0 +/- 0.3% of meal load, respectively; P: = 0.42). However, fasting RQ was significantly higher in the stunted group (0.92 +/- 0.009 compared with 0.89 +/- 0.007; P: = 0.04) and consequently, fasting fat oxidation was significantly lower (25 +/- 2% compared with 34 +/- 2% of energy expenditure; P: < 0.01). CONCLUSIONS: Childhood nutritional stunting is associated with impaired fat oxidation, a factor that predicted obesity in other at-risk populations. This finding may help explain recent increases in body fatness and the prevalence of obesity among stunted adults and adolescents in developing countries.

Body Composition↗
PubMed2000

Energy expenditure of stunted and nonstunted boys and girls living in the shantytowns of São Paulo, Brazil.

BACKGROUND: Stunting increases the risk of obesity in developing countries, particularly in girls and women, but the underlying reason is not known. OBJECTIVE: Our objective was to test the hypothesis that stunted children have lower energy expenditure than do nonstunted children, a factor that has predicted an increased risk of obesity in other high-risk populations. DESIGN: A cross-sectional study was conducted in shantytown children from São Paulo, Brazil. Twenty-eight stunted children aged 8-11 y were compared with 30 nonstunted children with similar weight-for-height. Free-living total energy expenditure (TEE) was measured over 7 d by using the doubly labeled water method. In addition, resting energy expenditure (REE) was measured by indirect calorimetry and body composition was measured by dual-energy X-ray absorptiometry. RESULTS: There were no significant associations between stunting and any measured energy expenditure parameter, including REE adjusted for weight (f1.gif" BORDER="0"> +/- SEM: 4575 +/- 95 compared with 4742 +/- 91 kJ/d, in stunted and nonstunted children, respectively) and TEE adjusted for weight (8424 +/- 239 compared with 8009 +/- 221 kJ/d, in stunted and nonstunted children, respectively). In multiple regression models that included fat-free mass and fat mass, girls had significantly lower TEE than did boys (P: < 0.05) but not significantly lower REE (P: = 0.17). CONCLUSIONS: There was no association between stunting and energy expenditure after differences between groups in body size and composition were accounted for. However, the girls had lower TEE than did boys, which may help to explain the particularly high risk of obesity in stunted adolescent girls and women in urban areas of developing countries.

Absorptiometry, Photon↗
PubMed2000

Regulation of energy intake may be impaired in nutritionally stunted children from the shantytowns of São Paulo, Brazil.

We tested the hypothesis that nutritionally stunted children have impaired regulation of energy intake (EI), a factor that could help explain the increased risk of obesity associated with stunting in developing countries. A 3-d residency study was conducted in 56 prepubertal boys and girls aged 8-11 y from the shantytowns of Sao Paulo, Brazil. Twenty-seven of the subjects were stunted and 29 were not stunted; weight-for-height Z-scores were not significantly different between the groups. Parents of the two groups had equivalent heights and body mass indices. Measurements were made of voluntary EI from a self-selection menu, resting energy expenditure (REE) and body composition. In addition, a 753-kJ yogurt supplement was administered at breakfast on one study day (with an equal number of children receiving the supplement on each of the 3 study days) and its effect on daily EI assessed. There was no change in EI over time in either group (P: = 0.957), and no significant difference in EI between stunted and nonstunted children, even though the stunted children weighed 10% less. Energy intake per kilogram body weight was significantly higher in the stunted children (278 +/- 89 (SD), vs. 333 +/- 67 kJ/kg, P: < 0.05) and EI/REE was also significantly higher (1.91 +/- 0.34 vs. 1.68 +/- 0.38, P: < 0.05). However, the relationship between EI and body weight was not significantly influenced by stunting (P: = 0.12). There was no significant effect of the breakfast supplement on daily EI in either group although the absolute difference in EI between supplement and control days was greater in stunted than in nonstunted children (DeltaEI: +460 +/- 1574 vs. -103 +/- 1916 kJ/d, P: = 0.25). These data provide preliminary evidence consistent with the suggestion that stunted children tend to overeat opportunistically, but further studies are required to confirm these results in a larger study.

Basal Metabolism↗
PubMed1999

Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy.

The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.

Alkyl and Aryl Transferases↗
PubMed1999

Toxicity of lead-contaminated sediment to mallards.

Because consumption of lead-contaminated sediment has been suspected as the cause of waterfowl mortality in the Coeur d'Alene River basin in Idaho, we studied the bioavailability and toxicity of this sediment to mallards (Anas platyrhynchos). In experiment 1, one of 10 adult male mallards died when fed a pelleted commercial duck diet that contained 24% lead-contaminated sediment (with 3,400 microgram/g lead in the sediment). Protoporphyrin levels in the blood increased as the percentage of lead-contaminated sediment in the diet increased. Birds fed 24% lead-contaminated sediment exhibited atrophy of the breast muscles, green staining of the feathers around the vent, viscous bile, green staining of the gizzard lining, and renal tubular intranuclear inclusion bodies. Mallards fed 24% lead-contaminated sediment had means of 6.1 microgram/g of lead in the blood and 28 microgram/g in the liver (wet-weight basis) and 1,660 microgram/g in the feces (dry-weight basis). In experiment 2, we raised the dietary concentration of the lead-contaminated sediment to 48%, but only about 20% sediment was actually ingested due to food washing by the birds. Protoporphyrin levels were elevated in the lead-exposed birds, and all of the mallards fed 48% lead-contaminated sediment had renal tubular intranuclear inclusion bodies. The concentrations of lead in the liver were 9.1 microgram/g for mallards fed 24% lead-contaminated sediment and 16 microgram/g for mallards fed 48% lead-contaminated sediment. In experiment 3, four of five mallards died when fed a ground corn diet containing 24% lead-contaminated sediment (with 4,000 microgram/g lead in this sample of sediment), but none died when the 24% lead-contaminated sediment was mixed into a nutritionally balanced commercial duck diet; estimated actual ingestion rates for sediment were 14% and 17% for the corn and commercial diets. Lead exposure caused elevations in protoporphyrin, and four of the five mallards fed 24% lead-contaminated sediment in a commercial diet and all five fed the contaminated sediment in a corn diet had renal intranuclear inclusion bodies. Lead was higher in the livers of mallards fed 24% lead-contaminated sediment in the corn diet (38 microgram/g) than in the commercial diet (13 microgram/g).

Administration, Oral↗
PubMed1998

Contaminants in eggs of colonial waterbirds and hepatic cytochrome P450 enzyme levels in pipped tern embryos, Washington State.

Eggs of Forster's terns (Sterna forsteri) collected in 1991 from nesting colonies on Crescent Island (Columbia River) and the Potholes Reservoir in south central Washington generally contained low residues of organochlorine pesticides and metabolites, 2,3,7, 8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran, and polychlorinated biphenyls (PCBs). Hepatic cytochrome P450 enzyme activity in pipped embryos of Forster's terns from the two colonies seemed unaffected by contaminants. At Crescent Island, examination of 23 Forster's tern eggs with large embryos (19 viable [10 pipped] and four dead [two pipped]) revealed developmental abnormalities in two viable pipped embryos (missing maxilla and deformed pelvic girdle) and a viable prepipping embryo (shortened beak). Our limited sample sizes and number of compounds analyzed preclude us from determining whether or not the abnormalities are related to contaminants. No abnormalities were noted in 10 pipped eggs (nine viable and one dead at collection) of Forster's terns collected from the Potholes Reservoir colony. Eggs of Caspian terns (Sterna caspia) collected from Crescent Island in 1991 also contained generally low residues of contaminants, only one developmental abnormality was noted, and limited data indicated that cytochrome P450 enzyme activity apparently was unaffected by contaminants. Organochlorine contaminants were generally low in addled eggs of American white pelicans (Pelecanus erythrorhynchos) collected from Crescent Island in 1994.

Animals↗
PubMed1998

The effects of diminishing albumin binding to some Endothelin receptor antagonists.

As a pharmacological class, Endothelin-A receptor (ET(A)) antagonists are highly bound (>98%) to serum albumin. In the presence of physiological concentrations of albumin, their affinities for ET(A) decrease 10 to 100 fold. We have prepared ET(A) antagonists which exhibit lower degrees of binding to albumin, while maintaining potency and selectivity for the ET(A) receptor. The protein induced IC50 shift is reduced or eliminated in this new series of compounds. The compounds also display altered in vivo and pharmacokinetic profiles which may be consistent with their lower degree of protein binding.

Animals↗
PubMed1997

Function of cell membranes in cerebral cortical tissue of newborn piglets after hypoxia and inhibition of nitric oxide synthase.

Hypoxia-induced brain cell membrane lipid peroxidation can be caused by free radicals that are produced during hypoxia. Recently, the production of nitric oxide (NO), a free radical, has been shown to be increased during cerebral hypoxia-ischemia. The present study tested the hypothesis that inhibition of NO synthase (NOS) reduced hypoxia-induced modifications of Na+,K+-ATPase activity, lipid peroxidation, and [3H]MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor in cerebral cortical tissue of newborn piglets. Studies were performed in 26 newborn piglets. Cerebral NOS was inhibited by the i.v. administration of 25 or 50 mg/kg N(omega)-nitro-L-arginine (NNLA) over 30 min. Control animals received normal saline. Six groups of piglets were thus created (normoxia, no NNLA; normoxia + NNLA 25 mg/kg; normoxia + NNLA 50 mg/kg; hypoxia, no NNLA; hypoxia + NNLA 25 mg/kg; hypoxia + NNLA 50 mg/kg). One hour after the start of NNLA or saline infusion, hypoxia was induced by lowering the FiO2 to 0.07 in the three hypoxia groups, whereas in the three other groups normoxia was maintained. After 60 min of hypoxia, the brain was taken out and frozen. NOS activity, Na+,K+-ATPase activity, conjugated dienes, and [3H]MK-801 binding to the NMDA receptor of cerebral cortical tissue were determined. NOS activity was reduced to 34% of its baseline value with NNLA 25 mg/kg, and to 19-27% of its baseline value with NNLA 50 mg/kg, respectively. Administration of NNLA did neither significantly alter the hypoxia-induced production of conjugated dienes, indicating lipid peroxidation nor the decrease of Na+,K+-ATPase activity after hypoxia. [3H]MK-801 binding studies of the NMDA receptor, however, showed that NNLA preserved Bmax and Kd after hypoxia. We conclude that inhibition of NOS does not change the hypoxia-induced decrease of Na+,K+-ATPase activity and production of conjugated dienes in brain cell membranes. Inhibition of NOS preserved the binding of [3H]MK-801 to the NMDA receptor after hypoxia.

Animals↗
PubMed1996

Cytosolic and membrane-bound cerebral nitric oxide synthase activity during hypoxia in cortical tissue of newborn piglets.

To determine the role of nitric oxide production during hypoxia, the presence of two forms of neuronal nitric oxide synthase, cytosolic (cNOS) and membrane-bound (memNOS), in cortical tissue of newborn piglets and the effects of hypoxia on the activity of these enzymes were studied. Experiments were performed in 12 anesthetized and ventilated Yorkshire piglets, 2-4 days of age. Hypoxia was induced by decreasing the FiO2 to 0.07. The control group was ventilated maintaining normoxia. After 1 h of normoxic or hypoxic ventilation brain tissue was removed and frozen immediately in liquid nitrogen. Tissue hypoxia was confirmed by analysis of adenosine triphosphate (ATP) and phosphocreatine (PCr): ATP was reduced to 52% and PCr to 28% of control values. cNOS activity was 35.3 +/- 13.7 pmol/mg protein per min in the control group and 28.3 +/- 7.0 in the hypoxia group; memNOS activity was 10.5 +/- 4.5 and 12.0 +/- 3.9 pmol/mg protein per min in the control and hypoxia groups, respectively. Differences in cNOS and memNOS activity between control and hypoxic animals were not significant. The results indicate that both cNOS and memNOS are present in cortical tissue of newborn piglets and that the activity is unaffected by 1 h of tissue hypoxia. We suggest that production of nitric oxide and its derivative peroxynitrite during hypoxia may therefore be a potential mechanism for hypoxia-induced brain cell membrane lipid peroxidation.

Analysis of Variance↗
PubMed1996

Azole endothelin antagonists. 3. Using delta log P as a tool to improve absorption.

The oral absorption profile of a family of azole-based ET(A)-selective antagonists has been improved through a rational series of structural modifications which were suggested by analysis of the physicochemical parameter delta log P. Comparison of urea 2 with a series of well-absorbed compounds using delta log P analysis suggested that 2 has an excess capacity for forming hydrogen bonds with solvent. A series of urea modifications were explored as a means of reducing H-bonding capacity while maintaining affinity for the ET(A)-receptor. The correlation between delta log P values and absorption in an intraduodenal (id) bioavailability model was good; this strategy uncovered replacements for each of the urea NH groups which simultaneously improve both potency and drug absorption. A combination of these optimized modifications produces carbamate 16h, a highly-selective ET(A) antagonist with a potency/bioavailability profile consistent with an oral route of administration.

Administration, Oral↗
PubMed1996

Developmental toxicity of PCB 126 (3,3',4,4',5-pentachlorobiphenyl) in nestling American kestrels (Falco sparverius).

Planar PCB congeners are embryotoxic and teratogenic to birds including American kestrels. The developmental toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) was studied in the posthatching kestrel as a model for the eagle. Nestlings were dosed orally for 10 days with 5 microl/g body weight of corn oil (controls) or the planar PCB 126 at concentrations of 50, 250, or 1000 ng/g body weight. Dosing with 50 ng/g of PCB 126 resulted in a hepatic concentration of 156 ng/g wet weight, liver enlargement and mild coagulative necrosis, over 10-fold increases in hepatic microsomal ethoxyresorufin-O-dealkylase and benzyloxyresorufin-O-dealkylase, and approximately a 5-fold increase in methoxyresorufin-O-dealkylase. At this dose, mild to moderate lymphoid depletion of the spleen was apparent, as were decreased follicle size and content of the thyroid. At 250 ng/g, concentration of PCB 126 in the liver was 380 ng/g with increasing multifocal coagulative necrosis, decreased bone growth, decreased spleen weight with lymphocyte depletion of the spleen and bursa, and degenerative lesions of the thyroid. At 1000 ng/g, the liver concentration was 1098 ng/g, accompanied by decreased bursa weight, decreased hepatic thiol concentration, and increased plasma enzyme activities (ALT, AST, and LDH-L) in addition to the previous effects. Highly significant positive correlations were noted between liver concentrations of PCB 126 and the ratio of oxidized to reduced glutathone. These findings indicate that nestling kestrels are more susceptible to PCB 126 toxicity than adults, but less sensitive than embryos, and that planar PCBs are of potential hazard to nestling birds.

Abnormalities, Drug-Induced↗
PubMed1996

Toxicity and oxidative stress of different forms of organic selenium and dietary protein in mallard ducklings.

Concentrations of over 100 ppm (mg/kg) selenium (Se) have been found in aquatic plants and insects associated with irrigation drainwater and toxicity to fish and wildlife. Composition of diet for wild ducklings can vary in selenium-contaminated environments. Earlier studies have compared toxicities and oxidative stress of Se as selenite to those of seleno-DL-methionine (DL) in mallards (Anas platyrhynchos). This study compares DL, seleno-L-methionine (L), selenized yeast (Y) and selenized wheat (W). Day-old mallard ducklings received an untreated diet (controls) containing 75% wheat (22% protein) or the same diet containing 15 or 30 ppm Se in the above forms except for 30 ppm Se as W. After 2 weeks, blood and liver samples were collected for biochemical assays and Se analysis. All forms of selenium caused significant increases in plasma and hepatic glutathione peroxidase activities. Se as L at 30 ppm in the diet was the most toxic form, resulting in high mortality (64%) and impaired growth (>50%) in survivors and the greatest increase in ratio of oxidized to reduced hepatic glutathione (GSH). Se as both L and DL decreased the concentrations of hepatic GSH and total thiols. Se as Y accumulated the least in liver (approximately 50% of other forms) and had less effect on GSH and total thiols. In a second experiment, in which the basal diet was a commercial duck feed (22% protein), survival was not affected by 30 ppm Se as DL, L, or Y and oxidative effects on GSH metabolism were less pronounced than with the wheat diet.

Animal Feed↗
PubMed1996

Toxicity of seleno-L-methionine, seleno-DL-methionine, high selenium wheat, and selenized yeast to mallard ducklings.

The toxicity of four chemical forms of selenium (seleno-L-methionine, seleno-DL-methionine, selenized yeast, and high selenium wheat) was compared in day-old mallard ducklings (Anas platyrhynchos). In the first experiment, in which the basal diet was 75% wheat, survival after 2 weeks was lower for ducklings fed 30 micrograms/g selenium as seleno-L-methionine (36%) than for ducklings fed 30 micrograms/g selenium as seleno-DL-methionine (100%) or 30 micrograms/g selenium from high selenium yeast (88%). The concentration of selenium at 2 weeks in the livers of survivors was similar for ducklings fed 15 micrograms/g selenium as seleno-DL-methionine (12 micrograms/g, wet weight), seleno-L-methionine (11 micrograms/g), and high selenium wheat (11 micrograms/g), but was lower when the selenium came from selenized yeast (6.2 micrograms/g). When fed 30 micrograms/g selenium from the various sources, the selenium concentrations in liver were 20 micrograms/g for seleno-DL-methionine, 19 micrograms/g for seleno-L-methionine, and 9.9 micrograms/g for selenized yeast. In a second experiment, in which the basal diet was a commercial duck feed, survival after 2 weeks was 100% in ducklings fed 30 micrograms/g selenium as seleno-DL-methionine, seleno-L-methionine, or selenized yeast. Selenium concentrations in liver were similar for ducklings fed the 30-micrograms/g selenium diets as the DL or L forms of selenomethionine (27 and 25 micrograms/g), but lower for ducklings fed selenized yeast (13 micrograms/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Endothelins and endothelin receptor antagonists: binding to plasma proteins.

Endothelins (ET) are 21-amino acid peptides that bind to membrane receptors to initiate a wide range of pathophysiological effects. PD-156707, L-749329, Ro-470203, and A-127722 are potent non-peptide ET receptor antagonists developed recently. When tested in human and rat plasma, both ET-1 and -3 and the four aforementioned antagonists exhibited a high degree (> 98%) of plasma protein binding. When ET-1 binding to the receptors was examined, 5% (v/v) of human plasma inhibited ET-1 binding to both ETA and ETB receptors by 80 - 90%. Similarly, 5% (w/v) of human serum albumin inhibited ET-1 binding by 82%, suggesting that the major protein component in plasma which interfered with ET-1 binding to the receptors was serum albumin. Competition studies show that, in the absence of human serum albumin, the IC50 values of PD-156707, L-749329, Ro-47-0203, and A-127722 were 0.37, 0.29, 5.7, and 0.22 nM, respectively. Addition of increasing doses of human serum albumin incrementally decreased the potency of the antagonists; in the presence of 5% of human serum albumin, the IC50 values increased to 62.8, 50.2, 122.7, and 6.72 nM for PD-156707, L-749329, Ro-47-0203, and A-127722, respectively. In conclusion, ET and ET receptor antagonists exhibit a high degree of binding to plasma proteins, especially serum albumin. Consequently, serum albumin inhibits ET binding to its receptors, and also decreases the potency of ET receptor antagonists. Our findings may explain the discrepancy observed for ET receptor antagonists between in vitro and in vivo potencies.

3T3 Cells↗