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Biomedical subjects

J Schroeder

Publications and source records attributed to J Schroeder.

At least 73 records · Page 4Linked to original sources
PubMed1989

Mono-2-ethylhexyl phthalate, a metabolite of di-(2-ethylhexyl) phthalate, causally linked to testicular atrophy in rats.

Acute testicular atrophy results when appropriate dosages of di-(2-ethylhexyl) phthalate (DEHP) or its hydrolysis product mono-2-ethylhexyl phthalate (MEHP) are given to male rats. Events thought to be involved in this pathological effect also occur in cultures of testicular cells in vitro, but require MEHP rather than DEHP. Primary cultures of hepatocytes, Sertoli cells, and Leydig cells were incubated with 14C-labeled MEHP [8 microM] for up to 24 hr. No significant reduction in viability was produced under these conditions. In contrast to the hepatocytes, which extensively metabolized MEHP to a variety of products in 1 hr, the testicular cell cultures were apparently unable to metabolize MEHP (beyond a slight hydrolysis to phthalic acid by Sertoli cells) in 18-24 hr. MEHP was efficiently taken up by hepatocytes, but much less so by testicular cells. These results, combined with related observations from the literature, support the hypothesis that MEHP itself is the metabolite of DEHP responsible for testicular atrophy in rats.

Animals↗
PubMed1988

Enhancement of Cu bioavailability in the rat by phytic acid.

The objective of this study was to evaluate the effect of phytic acid on copper (Cu) bioavailability. Male weanling rats were fed a Cu-deficient diet (less than 1.0 micrograms/g) for 4 wk and then were divided into 12 groups (n = 8) in a factorial design. Cu-deficient rats were then fed diets containing 1.4, 3.0, 5.2 or 10.5 micrograms Cu/g (CuCO3) and 0, 0.4 or 0.8% phytic acid as sodium phytate at each Cu level. All diets contained 30 micrograms Zn/g. After 3 d of Cu repletion, liver copper (LCu), liver Cu-Zn superoxide dismutase (LSOD) activity, serum Cu (SCu) and serum ceruloplasmin (CP) concentrations were determined. These parameters were used as indexes of Cu bioavailability. The addition of phytic acid to diets fed to Cu-deficient rats significantly enhanced Cu bioavailability compared to that of rats fed diets without phytic acid. Coefficients of determination (r2) were calculated for each response parameter versus dietary Cu concentration. The r2-values for pooled LCu and LSOD values were 0.31 and 0.30, respectively, between 1.4 and 5.2 micrograms Cu/g. At low dietary Cu concentrations, liver Cu parameters (i.e., LCu and LSOD) were more responsive indexes of Cu status than SCu and CP. Each index of Cu status was found to correlate with the other indexes of Cu nutriture. Phytic acid is postulated to enhance Cu utilization by its ability to bind other dietary components, such as Zn, that compete with Cu at the site of intestinal absorption.

Animals↗
PubMed1987

Beta-oxidation of 2-ethyl-5-carboxypentyl phthalate in rodent liver.

[7-14C]-2-Ethyl-5-carboxypentyl phthalate was isolated and purified from urine of rats given [7-14C]-di-(2-ethylhexyl) phthalate. This metabolite was shown to serve as a precursor for 2-ethyl-3-carboxypropyl phthalate in vivo. 2-Ethyl-5-carboxypentyl phthalate was oxidized to 2-ethyl-3-carboxypropyl phthalate in liver slices from control or, much more rapidly, from clofibrate-pretreated rats. Inhibition by KCN in liver slices from untreated rats, and strong inhibition by acrylate, suggested that formation of 2-ethyl-3-carboxypropyl phthalate involved mitochondrial beta-oxidation. The strong enhancement of the production of this compound by clofibrate (a very weak inducer for mitochondrial dehydrogenases), and strong inhibition by chlorpromazine suggested that peroxisomes may also be able to oxidize 2-ethyl-5-carboxypentyl phthalate. We were able to detect beta-oxidation of 2-ethyl-5-carboxypentyl phthalate to 2-ethyl-3-carboxypropyl phthalate using purified mitochondria, but strong phthalate monoester hydrolase activity observed during incubation of the former compound with purified peroxisomes made it impossible to determine whether 2-ethyl-3-carboxypropyl phthalate could be produced in the latter organelle or not. 2-Ethyl-5-carboxypentyl phthalate was such an inefficient substrate for beta-oxidation compared to palmitic acid that it is unlikely that it contributes significantly to the production of H2O2 in rats chronically exposed to di-(2-ethylhexyl) phthalate. Normal fatty acids are most likely to serve as the dominant substrates for peroxisomal beta-oxidase.

Animals↗
PubMed1987

Radiation enhancement of radiolabelled antibody deposition in tumors.

Recent clinical observations led to the use of external radiation to increase tumor targeting by radiolabelled 131-I antiferritin. Examination of increased uptake of 131-I labelled antiferritin following external radiation was carried out in syngeneic implanted hepatomas (H4IIE, 3924A, 7800, and 7777). Exposure to 10 Gy increased the tumor: liver uptake ratio from 1.55 to 1.86 for H4IIE; from 1.56 to 2.0 for 7800; from 1.34 to 1.97 for 7777; and from 1.05 to 1.19 for 3924A. The pattern of uptake varied among the different tumor types, reflecting their inherent differences in vascularity, tumor permeability, antigen density and growth rate, all of which influence antibody targeting of the tumors. When tumor and liver were irradiated, the tumor showed increased differential uptake of labelled antibody compared to normal liver. 51-Cr labelled erythrocytes were used to study the relative vascularity and blood pooling in H4IIE hepatoma and normal tissue. External radiation to the tumor did not increase the uptake of 51-Cr labelled erythrocytes in any site. These studies provide an insight into the role of external radiation as a modality that increases radiolabelled antibody targeting in hepatoma.

Animals↗
PubMed1986

Comparison of the efficacy and safety of esmolol, a short-acting beta blocker, with placebo in the treatment of supraventricular tachyarrhythmias. The Esmolol vs Placebo Multicenter Study Group.

The efficacy and safety of esmolol, a short-acting intravenous beta-adrenergic-blocking agent, and placebo were compared in patients with supraventricular tachyarrhythmias (heart rate greater than 120 bpm) in a multicenter, double-blind, partial-crossover study. Seventy-one patients were randomized to receive either esmolol (n = 36) or placebo (n = 35) as initial treatment. Therapeutic failures were crossed over to the other study medication. Therapeutic response was defined as greater than or equal to 20% reduction in heart rate, heart rate less than 100 bpm, or conversion to normal sinus rhythm. The therapeutic response to esmolol during the initial treatment period (72%) was similar to that obtained when esmolol was given as a second agent. The average esmolol dosage producing a therapeutic response was 97.5 micrograms/kg/min. Four patients (6%) converted to normal sinus rhythm during esmolol infusion. In the majority of patients (80%), therapeutic response was lost within 30 minutes following discontinuation of esmolol infusion, a finding indicative of rapid reversal of beta-adrenoceptor blockade. The most prevalent adverse effect during esmolol infusion was hypotension which occurred in eight patients (12%). Hypotension and associated symptoms resolved within 30 minutes after discontinuation of esmolol infusion, which is consistent with the short duration of action of esmolol (elimination half-life of 9.2 minutes).

Adrenergic beta-Antagonists↗
PubMed1985

Activation of nonspecific lipase (EC 3.1.1.-) by bile salts.

The enzyme nonspecific lipase (EC 3.1.1.-) from rat pancreas has been isolated and its amino acid composition determined. The amino acid composition confirms more indirect evidence that nonspecific lipase is not the same enzyme as cholesteryl ester hydrolase. Activation of the enzymatic activity by bile salts has been studied by equilibrium dialysis, gel filtration, light scattering, circular dichroism and fluorescence polarization. The binding of bile salt by the enzyme is saturable and is associated with a conformational change. Upon binding cholate, the protein experiences a decrease in beta-structure with no significant change in alpha-helix content, an increase in apparent Stokes radius, a decrease in light scattering properties, and a slight decrease in polarization of the intrinsic tryptophan fluorescence. Attachment of bile salt is associated with decreased reactivity of essential sulfhydryl groups, but no detectable change in reactivity of amino groups. A change to a more nearly spherical shape upon binding bile salt would be consistent with the experimental observations, but the exact sites of binding remain uncertain.

Amino Acids↗
PubMed1984

Comparison of the electrocardiographic effect of dothiepin and amitriptyline.

Electrocardiograms of 65 patients treated with dothiepin, a sulphur substituted tricyclic antidepressant, were compared to those of 57 patients receiving amitriptyline and 62 patients given placebo. Amitriptyline produced an average heart rate increase of 10 beats/minute as compared to 5 beats/minute for dothiepin (p less than .02). Amitriptyline also produced a significant prolongation of the corrected QT interval as compared to both dothiepin and placebo (p less than .01 and p less than .001, respectively). Dothiepin had no significant effect on any index of myocardial conduction (PR interval, corrected QT interval, and QRS duration) as compared to placebo.

Adult↗
PubMed1983

Polar metabolites of di-(2-ethylhexyl)phthalate in the rat.

Di-(2-ethylhexyl)phthalate (DEHP) is an important industrial chemical widely used as a plasticizer for vinyl and other plastics. DEHP is extensively metabolized by mammals, different species showing dramatic differences in metabolite distributions. Previous studies of the metabolism in rats led to the suggestion that the enzymatic processes normally associated with omega-, omega-1, alpha-, and beta-oxidation of fatty acids could account for the known metabolites of DEHP found in the urine. Several additional metabolites of DEHP have been identified in the present study. Their formation requires that the initial hydroxylation process be less specific than fatty acid omega- and omega-1 oxidation are thought to be. Furthermore, it is necessary to postulate either that the aliphatic chain of mono-(2-ethylhexyl)phthalate can be oxidized at two sites simultaneously, or that oxidation products can be recycled for a second hydroxylation prior to excretion.

Animals↗
PubMed1982

Applications of isotope differentiation for metabolic studies with di-(2-ethylhexyl) phthalate.

The pervasiveness of the plasticizer di-(2-ethylhexyl) phthalate (DEHP) in the environment and especially in the laboratory results in a background that may cause severe interference with analytical studies. Animal-to-animal variability in the distribution of DEHP metabolites in excreta normally makes it necessary to use large groups of animals when different treatments are compared. Finally, radioactive tracers are usually considered undesirable for metabolic studies involving human subjects. All of these problems can be overcome through the use of multiple isotopic labels, especially 12C/13C/14C. Examples are given involving rats and monkeys, and applicability to humans is discussed. The principles involved are not limited to any particular class of test compounds. In rats, the competing pathways for metabolism of phthalate esters produce a different distribution of metabolites from a small intravenous dose of DEHP than from a large oral dose.

Administration, Oral↗
PubMed1982

Histopathology of the cryptorchid testis.

Morphologic studies of cryptorchid testes do not show any pathologic changes other than one of malpositioning within the first year of life. Beginning with the third year of life histologic alterations become apparent in all structures. There is a marked increase in the number of mitochondria, which later degenerate and develop vacuoles. The endoplasmic reticulum loses its ribosomes almost completely. An enlargement of the perinuclear space develops between the lamellae of the nuclear membrane in the Sertoli cells and the spermatogonia. Light microscopy reveals a decrease in the number of spermatogonia and lack of development of the seminiferous tubules. The tunica propria is widened by a growing number of collagenous fibers, which become arranged in bundles.

Adolescent↗
PubMed1980

Spontaneous phasic activity of isolated human coronary arteries.

The functional behaviour and pharmacological responses of ring segments of large coronary arteries removed from five patients undergoing cardiac transplantation were studied in vitro. All segments showed spontaneous rhythmic contractions which were markedly dependent on external calcium and were rapidly abolished in calcium-free solutions and by verapamil. The contractions were inhibited by cooling and by anoxia. Phasic activity was enhanced by increasing the external potassium concentration over the range 5 to 20 mmol.litre-1 but was abolished by 120 mmol.litre-1 potassium. Noradrenaline and ergonovine enhanced or induced phasic activity. The behaviour of human coronary arteries resembles that of the portal-mesenteric veins of many species and our results suggest that the activation mechanisms of these two tissues may be similar.

Adult↗