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Biomedical subjects

D Steinberg

Publications and source records attributed to D Steinberg.

At least 397 records · Page 22Linked to original sources
PubMedDate not supplied

Formulation, development and characterization of sustained release varnishes containing amine and stannous fluorides.

This study describes properties of potential sustained release varnishes (SRV) containing amine fluoride or amine fluoride with stannous fluoride. The release kinetics, antibacterial properties and antiadhesion properties of two potential varnishes were tested. The varnish of ethylcellulose matrix was found to release fluoride for 4 h in vitro, while the formulation based on hydroxypropylmethylcellulose acetate succinate had a rapid release rate. Hydroxyapatite tablets coated with ethylcellulose-based SRV increased adhesion of Streptococcus mutans, while tablets coated with hydroxypropylmethylcellulose acetate succinate-based SRV decreased bacterial adhesion. Both types of SRV demonstrated a strong antibacterial effect on bacteria in biofilm.

Amines↗
PubMedDate not supplied

Lipoprotein lipase in cultured pig aortic smooth muscle cells.

Acetone powder extracts prepared from cultured pig aortic smooth muscle cells and the culture medium from these cells (particularly when incubated with heparin) were shown to contain a lipolytic enzyme which was identified as lipoprotein lipase by the following criteria: 1) stimulation by apolipoprotein C-II; 2) an optimal activity at approximately pH 8.0; 3) inhibition by NaCl, and 4) binding to a heparin-Sepharose affinity column. In addition, we found that cultured arterial smooth muscle cells from guinea pig and rabbit secreted a similar lipase into the culture medium. In contrast, studies using cultured bovine aortic endothelial cells yielded no evidence for either the synthesis or secretion of lipoprotein lipase by these cells. The production of lipoprotein lipase by the smooth muscle cells of the artery may play a role in the process of atherogenesis.

Acetone↗
PubMedDate not supplied

Enhanced macrophage degradation of biologically modified low density lipoprotein.

Low density lipoprotein (LDL) conditioned by incubation in the presence of rabbit aortic or human umbilical vein endothelial cells (endothelial cell-modified LDL) was degraded by macrophages three to five times more rapidly than LDL incubated in the absence of cells (control LDL). This enhanced degradation occurred mostly via a high affinity, saturable pathway related to the pathway for macrophage uptake of acetylated LDL. Conditioning LDL with cultured aortic smooth muscle cells had a qualitatively similar but smaller effect; conditioning with fibroblasts had no effect. Conditioning very low density lipoproteins or high density lipoproteins with endothelial cells did not affect subsequent metabolism of these lipoproteins by macrophages. Endothelial cell-modified LDL, while degraded more rapidly than control LDL by macrophages, was degraded more slowly by cultured smooth muscle cells and by human skin fibroblasts. Degradation of endothelial cell-modified LDL by macrophages was accompanied by stimulation of cholesterol esterification, inhibition of cholesterol synthesis, and a net increment in total cellular cholesterol content. Thus, a biologically generated modification of LDL is described that markedly alters cholesterol metabolism of macrophages and, consequently, may play a role in foam cell formation during atherogenesis.

Acetylation↗
PubMedDate not supplied

Neutral triglyceride lipase in macrophages.

High levels of neutral triglyceride lipase activity have been demonstrated in several types of macrophages (J774 cells, human monocyte/macrophages, rabbit alveolar macrophages, and resident mouse peritoneal macrophages). The pH optima ranged from 6.5 to 7.4 depending upon the buffer and the conditions of incubation. The addition of bovine serum albumin stimulated activity at low concentrations, as expected for a fatty acid-releasing reaction, but strongly inhibited at higher concentrations; maximal activity was observed in the presence of 0.625 mg/ml of bovine serum albumin. The enzyme was remarkably thermostable, showing no apparent loss of activity at 50 degrees C for as long as 6 hours. The lipase was inhibited 80% by 0.1 M NaCl. Assayed under optimal conditions, the specific activity of the neutral triglyceride lipase from J774 cells was more than 100-fold greater than the activity of lipoprotein lipase or neutral cholesterol esterase from those cells; this activity was 10-fold greater than the levels of hormone-sensitive lipase from 3T3-L1 adipocytes. This neutral triglyceride lipase may play an important role in the degradation and mobilization of cytosolic triglyceride in macrophage-derived foam cells.

Animals↗
PubMedDate not supplied

Measurement in vivo of irreversible degradation of low density lipoprotein in the rabbit aorta. Predominance of intimal degradation.

The development of a highly sensitive method for assessing, tissue by tissue, the rates of irreversible protein degradation in vivo has allowed us to quantify low density lipoprotein degradation in the normal rabbit aorta and to localize it. The method depends upon the fact that tyramine-cellobiose, like sucrose used in previous studies, can be covalently attached to proteins, enter cells with them, and then remains trapped within the cell after the remainder of the protein molecule has been degraded. Rabbit LDL (d = 1.02 to d = 1.06 g/ml) was labeled with 125I-tyramine-cellobiose and injected into rabbits. Aortic 125I content 24 hours later served as a cumulative measure of degraded LDL (after appropriate corrections for any intact, nondegraded LDL present). Calculated aortic degradation of LDL averaged 9.4 X 10(-3) percent of the plasma pool per g aortic wet weight per day (n = 6). Intimal cells, obtained by gentle swabbing, accounted for fully 40% of total aortic degradation even though the intima represented less than 5% of the aortic mass. Autoradiography confirmed the high concentration of label in the intima. Degradation of unmodified and reductively methylated LDL were compared. The fractional rate of degradation of methylated LDL by the intima was 50% to 60% of that for native LDL, indicating that 40% to 50% of LDL degradation in the intima, predominantly endothelial cells, is mediated by LDL receptors.

Animals↗
PubMedDate not supplied

Mobilization of stored triglycerides from macrophages as free fatty acids.

Because many or most lipid-laden foam cells in atheromas and in xanthomas derive from macrophages, it is important to understand how they accumulate lipids and how they can divest themselves of lipids. The mobilization of stored triglycerides from macrophages was studied in cell cultures. Mouse resident peritoneal macrophages and J774 macrophages increased their triglyceride content six- to tenfold during a 24-hour incubation with free fatty acids complexed to albumin. Subsequent incubation in fresh medium containing free fatty acid-poor albumin was accompanied by a fall in cell triglyceride content (50% in 20 hours) and a corresponding increase in medium-free fatty acid. Release of free fatty acid was linear as a function of time, provided fresh medium was added hourly. When medium was not changed, release rates fell off rapidly, probably due to re-uptake of released free fatty acid. Chloroquine did not affect the rate of free fatty acid release. The results suggest that macrophages-foam cells can reduce their triglyceride stores via the action of a nonlysosomal (presumably cytoplasmic) neutral triglyceride lipase.

Animals↗
PubMedDate not supplied

Role of the low density lipoprotein receptor in penetration of low density lipoprotein into rabbit aortic wall.

The present study was designed to determine whether binding of low density lipoprotein (LDL) to endothelial LDL receptors contributes significantly to the penetration of LDL into the normal rabbit aorta. Initial flux rate was used as a measure of uptake of LDL. Reductive methylation of LDL is known to block its recognition by the LDL receptor. Therefore, the difference in flux rates of native LDL and reductively methylated LDL (methyl-LDL) was assumed to represent the receptor-dependent uptake. Native LDL and methyl-LDL were labeled with different isotopes (125I or 131I) and both were injected simultaneously into the same rabbit. After 30 to 60 minutes, trichloroacetic acid-precipitable counts were determined in aortic specimens. The initial flux rates, expressed as plasma clearance (nl/g/hr), were 1787 for native LDL and 1924 for methyl-LDL. The difference was not significant, which suggests that the flux of LDL into the aorta is not significantly dependent upon, or regulated by, endothelial LDL receptors, but is mediated by other mechanisms.

Animals↗
PubMedDate not supplied

Macrophage oxidation of low density lipoprotein generates a modified form recognized by the scavenger receptor.

Incubation of low density lipoprotein (LDL) with endothelial cells or smooth muscle cells overnight has resulted in an oxidative modification of LDL that results in its recognition by macrophages by way of the acetyl LDL receptor. In the present study, we examined whether macrophages themselves can oxidize and modify LDL in a manner similar to that of endothelial cells. Incubation of 125I-labeled LDL with resident or thioglycollate-elicited macrophages for 24 hours in Ham's F-10 medium resulted in the appearance of thiobarbituric acid (TBA) reactive materials and trichloroacetic acid (TCA) soluble radioactivity in the medium. The LDL harvested from these incubations showed increased electrophoretic mobility and was degraded rapidly when added to fresh macrophages as compared to LDL previously incubated in the absence of cells. These macrophage-induced modifications could be prevented if the first incubation was carried out in the presence of the antioxidant butylated hydroxytoluene (BHT) or in Dulbecco's modified Eagle's medium (DMEM). The degradation of 125I-labeled macrophage-modified LDL by macrophages was competitively inhibited by unlabeled acetyl LDL or unlabeled endothelial cell-modified LDL but not by native LDL, indicating that the degradation was mediated by the acetyl LDL receptor.

Animals↗
PubMedDate not supplied

Decrease in reactive amino groups during oxidation or endothelial cell modification of LDL. Correlation with changes in receptor-mediated catabolism.

The monocyte/macrophage appears to be the precursor of many of the lipid-laden cells in atherosclerotic lesions, but the mechanism by which these cells accumulate cholesterol to become foam cells remains unclear. We have previously reported that cultured endothelial cells can modify low density lipoprotein (LDL) in a manner that leads to rapid uptake by the acetyl LDL receptor of macrophages. This modification involves free radical-induced peroxidation of LDL and is accompanied by many changes in the physicochemical properties of LDL including increased electrophoretic mobility, increased density, decreased content of esterified cholesterol, hydrolysis of phosphatidylcholine, and fragmentation of apolipoprotein B. Under conditions highly favorable to oxidation, a similar modification can occur even in the absence of cells. In the present studies, oxidation of LDL simply by exposure to 5 microM Cu++ resulted in a modification that was indistinguishable from that produced by endothelial cells. Moreover, it was demonstrated that LDL oxidation by either method is accompanied by a marked decreased in amino group reactivity, comparable to that seen with the chemical modifications of LDL that lead to recognition by the acetyl LDL receptor. Inhibitors of proteolytic enzymes did not reduce fragmentation of apolipoprotein B during oxidation. The rate of catabolism of intravenously injected oxidized LDL in guinea pigs was very rapid, and over 80% of the degradation occurred in the liver. The studies demonstrate that all of the changes associated with endothelial cell modification of LDL can be attributed to oxidation. The cells can, however, promote oxidation under conditions where it would otherwise occur very slowly.(ABSTRACT TRUNCATED AT 250 WORDS)

Amines↗
PubMedDate not supplied

Enhanced macrophage uptake of low density lipoprotein after self-aggregation.

Incubation of mouse peritoneal macrophages with native human low density lipoprotein (LDL) did not cause any significant storage of intracellular cholesteryl esters. However, when the LDL was subjected to brief (30-second) vortexing, it formed self-aggregates that were rapidly ingested and degraded by macrophages, converting them to cholesteryl ester-rich foam cells. Such aggregates were as potent as acetyl-LDL in stimulating cholesterol esterification in the macrophages. The degradation of LDL aggregates was strongly inhibited by cytochalasin B (85%), whereas degradation of native LDL was only weekly inhibited (23%), suggesting that uptake occurred by phagocytosis rather than pinocytosis. Several lines of evidence suggest that the phagocytic uptake depends, in part, upon the LDL receptor and not the acetyl-LDL receptor: 1) soluble, native LDL and beta-VLDL (but not acetyl-LDL) competed for uptake and degradation of LDL aggregates; 2) reductive methylation of LDL before vortexing reduced the effect of the aggregates on degradation and cholesterol esterification; 3) heparin, which inhibits binding of native LDL to its receptor, reduced the degradation of LDL aggregates. These studies show that self-aggregation of LDL markedly enhances its uptake by macrophages, probably by phagocytosis and at least, in part, via the LDL receptor. Aggregates of LDL in the artery wall--either self-aggregates or mixed aggregates including matrix components--may induce foam cell formation and favor the formation of the fatty streak.

Animals↗
PubMedDate not supplied

Oxidative modification of beta-very low density lipoprotein. Potential role in monocyte recruitment and foam cell formation.

Oxidative modification of low density lipoprotein (LDL) generates a form that is degraded much more rapidly by macrophages and may thus be more atherogenic than unoxidized LDL. Recently, we provided evidence that oxidative modification of LDL may play a significant role in the generation of fatty streaks in the LDL receptor-deficient rabbit. The major lipoprotein in cholesterol-fed animals is the beta-very low density lipoprotein (beta-VLDL). Since beta-VLDL is avidly taken up by macrophages, it could lead to foam cell formation without the need for oxidative modification or modification of other kinds. However, the present studies show that beta-VLDL can be oxidized by incubation with endothelial cells or with copper ions. Oxidized beta-VLDL was degraded by macrophages at about twice the rate of unoxidized beta-VLDL, and it stimulated cholesterol esterification twice as much as unoxidized beta-VLDL. The degradation of oxidized beta-VLDL was inhibited either by oxidized beta-VLDL itself or by oxidized LDL, but not by unoxidized beta-VLDL. beta-VLDL was chemotactic for human monocytes and contained significant amounts of lysophosphatidylcholine, previously shown to be a chemotactic agent. In summary, oxidized LDL is degraded by macrophages proportionately more than oxidized beta-VLDL as compared to the unmodified lipoproteins. However, the twofold increase may, nevertheless, be significant in the atherogenicity of beta-VLDL.

Animals↗
PubMedDate not supplied

Anemia and cancer.

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Anemia↗
PubMedDate not supplied

Inhibition of plaque accumulation under periodontal dressing by sustained-release varnish of chlorhexidine.

Slow-release varnish containing chlorhexidine was applied prior to the application of a periodontal dressing. The ability of the slow-release varnish to inhibit accumulation of dental plaque under the dressing was compared to a placebo varnish. Seven volunteers were fitted with periodontal dressing on the lower and upper jaws. One jaw was pre-coated with slow-release varnish containing chlorhexidine, while the other was coated with a placebo. A week later the dressings were removed and the plaque under the dressing was scored. Significantly less plaque was found on teeth pre-coated with the slow-release varnish containing chlorhexidine as compared to the control. An increase in the amount of gingival fluid was observed in both the control and experimental groups after removing the periodontal dressing.

Adult↗
PubMedDate not supplied

[Rocuronium: onset time or speed of action?].

OBJECTIVE: Rocuronium has been said to have an initially rapid onset of action followed by a slower final approach to maximum effect, the supporting data showing only that time to 75% of blockade is more rapid. Expressions of velocity are derived from basic measures such as length and time. The aim of our study was to confirm the onset characteristics of rocuronium by using appropriate expressions of velocity. PATIENTS AND METHODS: After consenting, 25 adults scheduled for elective surgery were anesthetized, using a bolus dose of rocuronium of 400 microg Kg(-1) for relaxation. Electromyography was used to determine maximal effect, time to reach 80% of a full neuromuscular block, onset time, the time interval between these two points, and the differential blockade produced during each period. Velocity for each period was calculated as the ratio between the percentage of block produced per amount of time elapsed (%/s) during each respective period. The ratio between time and blockade (s/%) was also calculated. RESULTS: More blockade was produced per second (velocity) during the initial period of activity (0.55%/s) than during the final period (0.109%/s). The average velocity during the onset period overall (0.33%/s) lay between those two figures. Rocuronium requires less time (acting fast) to achieve an initial effect (1.95 s/%) than it does to reach the final effect (10.8 s/%). The ratio of early to late speed of onset was 5.8 +/- 3.5. CONCLUSION: Using appropriate expressions and calculations, we can unequivocally conclude that rocuronium has a biphasic onset that is initially rapid and then slower. The rate of action is nearly 6 times faster at the beginning.

Androstanols↗
PubMedDate not supplied

The effect of sustained-release varnish of chlorhexidine in dental plastic shells on salivary Streptococcus mutans.

The suppression of S. mutans is a predominate factor in preventing tooth decay. Sustained-release-delivery varnish of chlorhexidine was applied to dental plastic shells and administered to eight volunteers to be worn while sleeping. Salivary bacterial samples were taken on days 0, 7, 14, 21, 28, 35. A statistically significant reduction in S. mutans counts was recorded during the course of the study while a non-significant reduction in the total bacterial counts was found. Our results indicate that the application of chlorhexidine in the form of slow-release varnish in plastic shells is an effective intraoral drug delivery system resulting in reduction of S. mutans.

Chlorhexidine↗
PubMedDate not supplied

Topical varnish containing strontium in a sustained-release device as treatment for dentin hypersensitivity.

The purpose of this study was to assess the effect of topical application of a sustained-release device in form of a varnish containing strontium chloride on dentinal hypersensitivity. Sixty teeth were selected in ten patients. The teeth were divided in a) varnish application containing strontium chloride, b) varnish application with no active ingredient, c) untreated teeth. Varnish application was carried out by the patients once daily for 30 days. Results show a marked decrease in hypersensitivity to both mechanical (54%) and thermal stimuli (38%) as compared to the placebo and untreated group.

Delayed-Action Preparations↗