PubMed HealthSearch

Biomedical subjects

A H Goldberg

Publications and source records attributed to A H Goldberg.

At least 19 recordsLinked to original sources

Selective adherence of a sucralfate-tetracycline complex to gastric ulcers: implications for the treatment of Helicobacter pylori.

The adherence of a sucralfate-tetracycline complex to gastric ulcers and to nearby non-ulcer sites was determined in the rabbit antrum. Persistent gastric ulcers were produced by a previously described method. The presence of the complex was assessed 1 and 4 h after dosing. Drug adherence was determined by quantitation of aluminum in stomach wall biopsies. Significantly more aluminum adhered to ulcer sites than to nearby non-ulcer sites. Adherence of the complex did not significantly decrease from 1 to 4 h. The complexation of tetracycline to sucralfate did not alter the selective adherence of sucralfate to gastric ulcers, providing a mechanism of ulcer site-selective drug delivery in the treatment of Helicobacter pylori gastric ulcer disease.

Aluminum

Viscoelastic properties of poly(ethylene oxide) solution.

The viscoelastic properties of poly(ethylene oxide) (PEO) solution were investigated using the dynamic oscillatory testing technique. With this technique, the effect of PEO molecular weight (MW), concentration, composition of mixed solvent systems consisting of propylene glycol, glycerol formal, and water, and the effect of NaCl salt on the viscoelastic properties of PEO solution were determined. Dynamic moduli (G1, G2), magnitude of complex viscosity (magnitude of eta*), and loss tangent (tan delta) were examined over a frequency range of 10(-3)-2.5 Hz at 30 degrees C. The results indicated that low MW PEOs show liquidlike behavior while high elasticity is exhibited by high MW PEOs due to entanglement formation. The complex viscosity, magnitude of eta*, exhibits shear thinning (power-law) characteristics under oscillatory measurements. The relationship between steady shear and complex viscosities follows the Cox-Merz rule over the shear rate and frequency region studied. Both the storage (G1) and loss (G2) modulus increase drastically as the proportion of water in the mixed solvent system increases. Similarly, both G1 and G2 are found to increase while the tan delta decreases with increasing concentration of PEOs. The addition of up to 2% w/w NaCl in an aqueous solution of 10% w/w 2 million MW PEO has no observed detrimental effect on the viscoelastic behavior.

Chemical Phenomena

The role of rheological properties in mucociliary transport by frog palate ciliated model.

The effect of viscoelastic properties on mucociliary transport rate was investigated using the frog palate ciliated model. Mucociliary transportability of several hydrophilic polymeric gels with widely different viscoelastic characteristics were tested on the frog palate mucociliary model. An apparent negative relationship is observed between the relative transport rate (TR) and storage (G1) or loss (G2) modulus. However, a minimum in relative transport rate is observed at an apparent loss tangent (tan delta) value of between 0.7 and 0.9. A theoretical model for mucociliary transport is presented. The model predicted a minimum in transport rate at tan delta equal to 1.74 after adjustment for primary variation due to storage modulus (G1), which is in agreement with the observed frog palate transport rate. The model isolates the loss tangent (tan delta) and the magnitude of the complex modulus (magnitude of G*) as the important viscoelastic parameters for mucociliary transport. Optimum rheological characteristics with respect to slow transport rate can be achieved by using hydrophilic polymer gels with a large complex modulus and simultaneously with a loss tangent equal to 1.74.

Animals

Diltiazem and regional left ventricular function during graded coronary constriction and propofol anesthesia in the dog.

Although calcium channel blockers may preserve function in ischemic myocardium, they may also produce myocardial depression and dysfunction in the presence of decreased coronary flow. This study was designed to examine the issue of possible protection afforded by diltiazem against ischemia-induced myocardial dysfunction during propofol anesthesia. In eight anesthetized and ventilated dogs, regional myocardial (ultrasonic crystals in both left anterior descending [LAD] and left circumflex [LC] perfusion areas) and global ventricular function were evaluated during progressively severe degrees of myocardial ischemia (LAD constriction) before and after intravenous diltiazem (150 micrograms/kg). As coronary flow decreased, heart rate increased, and arterial and coronary perfusion pressures, left ventricular dP/dt, and cardiac output decreased. Systemic vascular resistance was unaffected. Diltiazem without coronary constriction increased heart rate, and decreased diastolic arterial pressures, left ventricular (LV) end-diastolic, coronary perfusion pressures, LV dP/dt max, LAD coronary blood flow, stroke volume, and cardiac output. At all levels of coronary constriction following diltiazem, there were decreases in systolic and diastolic arterial pressures, stroke volume, cardiac output, LV dP/dt, and coronary perfusion pressure. Heart rate increased at critical coronary constriction, and then remained constant relative to the prediltiazem state. The regional muscle effects of the reductions in coronary flow in the LAD perfusion territory included decreased systolic shortening and increased postsystolic shortening before and after diltiazem. Diltiazem did not alter the magnitude of the alterations in systolic or postsystolic shortening brought about by coronary constriction. No changes occurred in the LC area.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous

Effects of 2,3-butanedione monoxime in isolated hearts: protection during reperfusion after global ischemia.

The cardiac effects of 2,3-butanedione monoxime on electrical and mechanical function, rhythm, oxygen utilization, and coronary flow responsiveness, particularly during severe ischemia and reperfusion, have not been studied. After perfusing hearts at 55 mm Hg, coronary perfusion was interrupted for 30 minutes and was then reestablished at the control perfusion pressure for 40 minutes. Hearts were divided into four groups (n = 10 each) treated with 0, 3, 5, or 10 mmol/L of 2,3-butanedione monoxime added to the perfusate for 10 minutes before and during ischemia and for the first 10 minutes of reperfusion. An additional nonischemic group served as a time control. Variables monitored were heart rate, atrioventricular conduction time, cardiac rhythm, isovolumetric systolic and diastolic left ventricular pressure, maximum rate of left ventricular pressure change, coronary flow, myocardial oxygen consumption, and the ratio of oxygen delivery to myocardial oxygen consumption. Before ischemia, 2,3-butanedione monoxime significantly decreased isovolumetric left ventricular systolic pressure and increased the ratio of oxygen delivery to myocardial oxygen consumption in a dose-dependent manner, with only slight changes in heart rate and atrioventricular time with 10 mmol/L of 2,3-butanedione, monoxime. After 40 minutes of reperfusion, isovolumetric left ventricular systolic pressure recovered to 81 +/- 5% and 83 +/- 2% of the initial control values for the 5 and 10 mmol/L 2,3-butanedione monoxime groups. This was significantly greater than the recovery for the 0 and 3 mmol/L 2,3-butanedione monoxime groups, 59 +/- 3% and 63 +/- 4%, respectively. Similarly, the duration of ventricular fibrillation and of tachycardia was significantly lower, coronary flow reserve was better preserved, and myocardial oxygen consumption was greater with reperfusion in the 5 and 10 mmol/L 2,3-butanedione monoxime groups than in the 0 mmol/L 2,3-butanedione monoxime group. This study shows that relatively low concentrations of 2,3-butanedione monoxime, given before global ischemia and early during reperfusion of isolated hearts, can protect against dysrhythmias and improve return of myocardial and vascular function.

Animals

Canine end-systolic pressure-length relationships: depressed by diltiazem, invalidated by ischemia.

This study was designed to determine whether the end-systolic pressure-length relationship (ESPLR) reflects changes in regional contractility during the imposition of graded ischemia, and whether it is modified by diltiazem during propofol anesthesia. Seven beagles were anesthetized and instrumented to measure left ventricular pressure and subendocardial segment lengths (sonomicrometry) in the region of the left anterior descending (LAD) and circumflex (LC) arteries. Afterload was increased by the tightening of a snare around the descending thoracic aorta. Pressure-length loops were constructed and the slope of the ESPLR and the x-axis intercept, Lo, were calculated. Graded ischemia of the apical myocardium only was accomplished by the tightening of a micrometer-controlled snare around the LAD to produce Critical Constriction (CC), Ischemia 1 and 2 (I1, I2), and Total Occlusion (TO). In the basal LC region, LAD ischemia had no effect on either the ESPLR slope or Lo. In contrast, the ESPLR slope in the LAD area was decreased by ischemia at I1 (-40%), increased at TO (+69%), and unchanged at CC and I2, and was reduced by diltiazem at CC and I2 (-31% and -36%, respectively). The LAD ESPLR Lo was increased by ischemia by 64% and 61% at I2, and 91% and 122% at TO, before and after diltiazem, respectively. In the LC region, diltiazem decreased systolic shortening and the ESPLR slope. These results indicate that diltiazem has negative inotropic properties in both ischemic and nonischemic areas. Also, Lo is not a constant and must always be redetermined for every intervention. In the absence of ischemia, the ESPLR may be a reliable measure of myocardial contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Viscoelastic properties of polyacrylic acid gels in mixed solvents.

The objective of this study is to investigate the viscoelastic properties of Carbopol 934P polymeric systems in a variety of mixtures of pharmaceutical solvents. Carbopol 934P neutralized with a 1:1 equivalent ratio of triethanolamine was dissolved in various binary or ternary solvent mixtures consisting of propylene glycol, glycerol formal, and water. Dynamic moduli G' and G'', complex viscosities, eta' and eta'', and loss tangent, tan delta, were examined over a frequency range of 10(-3) to 10 Hz using an oscillatory viscoelastic rheometer at 30 degrees C. The results indicated that for 0.5-1.5 wt% neutralized Carbopol in ternary mixtures, G' and G'' increased by 3-4 orders of magnitude and the phase angle decreased from 80 to 25 degrees when the water content in the solvent mixture increased from 10 to 80 wt%. These studies also indicated that the addition of water to nonaqueous Carbopol 934P polymer systems transforms them from low-viscosity solutions to gels with significant elastic behavior involving physical interaction and entanglement of polymer segments with solvents.

Acrylic Resins

Viscometric study of polyacrylic acid systems as mucoadhesive sustained-release gels.

This report describes a novel nonaqueous polymeric formulation that exhibits low-viscosity fluid behavior for ease of spraying with conventional nebulizer, which when sprayed into the nasal cavity, transforms to a high-viscosity gel for efficient retention and drug absorption. The transformation occurs because of the rheological changes induced by a change in the solvent composition of the polymeric formulation in the moist nasal cavity. Such a rheological change would then facilitate enhanced residence time of the drug at the site of administration in order to avoid drainage losses. This study reports the results of the effects of a variety of factors such as solvent composition and polymer concentration on the rheological properties of a polyacrylic acid polymer. An attempt to correlate viscosity enhancement effects with enhanced and sustained-release behavior of propranolol, a drug that undergoes extensive first-pass effects, from such formulations via nasal administration in beagle dogs is also described.

Acrylic Resins

Mixture experimental design in the development of a mucoadhesive gel formulation.

The objective of the present study is to apply response surface methodology to the design and analysis of composite experiments containing independent covariate(s). The approach is illustrated here by the study of viscosity characteristics of a polymeric mucoadhesive formulation in multicomponent solvent vehicles. The nonaqueous formulation will produce a gel network with significant rheological change when in contact with body fluids. The process of water inclusion will induce not only solvent compositional change of the mixture but also concomitant dilution of the polymer concentration. To study the viscosity change over the solvent compositions and polymeric concentrations of interest, an experimental design is utilized consisting of a 10-point simplex-centroid lattice augmented with three interior points at each polymeric concentration. The contour patterns are compared with the experimental data using the variance and lack of fit, starting with the Scheffe linear model and building up to the full cubic model including the covariate terms. The fitted model provides information needed to predict optimum formulations, i.e., initial viscosity of less than 100 cP, but yielding rheological profiles commensurate with high degrees of substantivity when diluted with water. For illustrative purposes, the Carbopol resins neutralized with a 1:1 molar equivalent ratio of triethanolamine in three primary solvents, propylene glycol, glycerol formal, and water, were chosen for this study.

Acrylic Resins

Contractile properties of fast muscle preparations regenerating in slow muscle beds.

Mechanical evidence is presented to show that fast muscle tissue regenerating in the bed of a slow muscle, and innervated by the slow muscle nerve, has contractile properties identical to those of a slow muscle regenerating in its own bed. The results do not support the idea that regenerating fast muscles are partially resistant to the transforming effects of a slow nerve.

Animals

Chromatin-associated glycoproteins of normal rat liver and Novikoff hepatoma ascites cells.

Glycoproteins were demonstrated in the 0.6 M NaCl extract of chromatin of normal liver and Novikoff hepatoma cells by periodic acid-Schiff staining of sodium dodecyl sulfate-polyacrylamide gels. In chromatin extracts of Novikoff hepatoma cells, six major periodic acid-Schiff-positive bands coincident with Coomassie Blue-stained protein bands were found with molecular weights of 30,000, 54,000, 64,000, 75,000, 104,000, and 127,000. A corresponding extract from normal rat liver chromatin revealed the presence of four major periodic acid-Schiff-positive bands that migrated with protein bands at molecular weights of 16,000, 30,000, 54,000, and 75,000. The glycoproteins of these extracts contained either mannose or alpha-D-glucose, fucose, and N-acetylglucosamine as shown by the specificity of lectins in affinoelectrophoresis. One of the glycoproteins detected by affinoelectrophoresis was very basic.

Animals

Isolation and characterization of nonhistone chromosomal protein C-14 which stimulates RNA synthesis.

The nonhistone chromatin protein, C-14, was extracted from chromatin of Novikoff hepatoma ascites cells and isolated in high purity as shown by its migration as a single dense spot on two-dimensional polyacrylamide gels. Its mobility on sodium dodecyl sulfate gels is consistent with a molecular weight of approximately 70 000. The amino acid composition shows that protein C-14 has an acidic:basic amino acid ratio of 1.8. Its amino terminal amino acid is lysine. Protein C-14 stimulated the incorporation of [3H]UMP into RNA by approximately 30% when added to naked DNA and homologous RNA polymerase I. A 30% stimulation of [3H]UMP incorporation into RNA was also found when protein C-14 was added to an E. coli RNA polymerase system containing either E. coli or Novikoff hepatoma DNA.

Amino Acid Sequence

The effects of halothane on pregnant and nonpregnant human myometrium.

Strips of myometrium were obtained at operation from eight nonpregnant and ten pregnant patients. The tissues were immediately suspended in a muscle bath and induced to contract isometrically with K2SO4 in the presence and absence of halothane (0.5 to 2.0 vol per cent). The anesthetic produced significant dose-related depression of developed tension and rates of increase and decrease of tension in both pregnant and nonpregnant muscles. Time to peak tension was increased in the nonpregnant but not in the pregnant muscles. The depressant effect of the lower halothane concentrations (less than 1.1 vol per cent) was significantly greater in the pregnant muscles.

Adolescent

Halothane and calcium interaction in isolated pregnant and postpartum rat myometrium.

Isolated strips of mid-pregnant and postpartum rat myometrium were rendered functionally Ca2+-free by exposure to a Ca2+-free modified Krebs-bicarbonate solution containing 1 mM EGTA. The muscle strips were then exposed to 2.25 mM Ca2+ for periods of 15 to 600 seconds for the mid-pregnant tissues and one 120-second period for the postpartum tissues. At the end of each exposure, Ca2+ was removed and simultaneously each muscle was depolarized with 125 mM K2SO4. Isometric tension changes in the muscles were measured with and without 0.5 per cent halothane. In the mid-pregnant muscles, halothane diminished the initial tension development in response to Ca2+ by approximately 50 per cent, regardless of the duration of Ca2+ exposure. The contractile response of these muscles to depolarization with K2SO4 was reduced 10 per cent by 0.5 per cent halothane; this was probably due to reduction in transmembrane influx of Ca2+. In the postpartum muscles, the initial tension development in response to Ca2+ was threefold greater than in mid-pregnant muscles and was reduced 25 per cent by halothane. These tissues failed to develop by any tension in response to K2SO4. The most likely explanation for the effect of halothane is that it reduces the transmembrane influx of Ca2+ in both types of tissues, but that the postpartum sarcoplasmic reticulum present less competition for intracellular Ca2+ than pregnant sarcoplasmic reticulum.

Animals

Heart muscle performance after experimental viral myocarditis.

As part of an inquiry into possible antecedents of idiopathic cardiomyopathy, acute experimental coxsackie virus myocarditis was studied for late structural and functional sequelae. Myocarditis was induced in 12- and 22-day-old hamsters by inoculation with coxsackie virus B3. Early viremia occurred, followed by virus replication in heart muscle. Maximum peak developed tension (Tpd) of isometrically contracting isolated heart muscle was depressed 17 and 43% in the animals inoculated at 12 days, and studied 18 and 90 days later, respectively, as compared to their uninoculated controls. In both infected groups, less muscle stretch was required to reach the length at which Tpd was produced. Animals studied 180 days after inoculation did not differ from controls. The muscles from animals inoculated at 22 days of age and studied 18 days later showed a 15% depression of Tpd compared to their controls. Glycerinated muscles from this infected group developed 50% less tension than their controls. The muscles of hamsters inoculated with virus at 22 days and studied 90 and 180 days later showed no change in Tpd. The data suggest that contractility and compliance of heart muscle are decreased 18 days after inoculation, but recover by 90 days if the animals are inoculated at age 22 days. However, if the animals are inoculated at a younger age (12 days), depression of myocardial performance persists for at least an additional 90 days. It is concluded that the inflammatory stage of experimental acute coxsackie virus B3 myocarditis in the Syrian golden hamster may be followed by residual alterations in contractile proteins and myocardial function.

Animals