Search PubMed⌕ Search

Biomedical subjects

J Newburger

Publications and source records attributed to J Newburger.

18 recordsLinked to original sources
PubMed1992

Quantitation of lysophosphatidylcholine molecular species in rat cardiac tissue.

We have developed a rapid and sensitive procedure for isolation and measurement of 1-acyllysophosphatidylcholine (LPC) species in rat myocardial tissue. Tissues were spiked with heptadecanoyl-LPC internal standard and extracted with chloroform/methanol. The chloroform phase was dried, resuspended in chloroform/propan-2-ol (2/1, v/v), and applied to an aminopropyl-bonded phase (Bond Elut) column. Following stepwise elution with several solvent mixtures, the LPC fraction (ethyl acetate/methanol, 4/6, v/v) was separated by HPLC with direct quantitation of palmitoyl-LPC (P-LPC), oleoyl-LPC (O-LPC), and stearoyl-LPC (S-LPC), using an evaporative light scattering mass detector. Calibration curves were generated for each individual LPC species. Recoveries of added [14C]LPC and of heptadecanoyl-LPC internal standard after extraction and chromatography were 85.8 +/- 1.9% (mean +/- SE, N = 10) and 83.4 +/- 1.8% (N = 15), respectively. This assay showed satisfactory sensitivity, reproducibility, and accuracy for measurement of LPC species in rat myocardial tissue. The major molecular species of LPC in rat myocardium were found to be P-LPC and S-LPC, which were two- to sixfold as abundant as O-LPC. In isolated, crystalloid-perfused rat hearts the time of perfusion was found to significantly influence the content of P-LPC (0 min, 252 +/- 10; 15 min, 178 +/- 10, P less than 0.001, compared with 0 min; 40 min, 131 +/- 4, P less than 0.001; and 70 min, 129 +/- 4, P less than 0.001; nmol/g dry weight), but not the content of O-LPC and S-LPC. The method will be useful for studying the participation of LPC species in physiology, pathophysiology, and therapeutics.

Animals↗
PubMed1991

Cardioprotective effects of the potassium channel opener cromakalim: stereoselectivity and effects on myocardial adenine nucleotides.

We determined if the cardioprotective effects of the potassium channel opener cromakalim are stereoselective and if it can preserve adenine nucleotides in ischemic myocardium. We subjected isolated isovolumically beating rat hearts to 25 min of global ischemia and reperfusion with and without pretreatment by cromakalim or its enantiomers. All of these compounds significantly increased preischemic coronary flow with the (3S,4R)-(-)-enantiomer being more potent (EC25 = 0.52 microM) compared to cromakalim (EC25 = 1.04 microM) and the (3R,4S)-(+)-enantiomer (EC25 greater than 100 microM). The (-)-enantiomer was also significantly more potent in reducing ischemic/reperfusion damage compared to cromakalim and its (+)-enantiomer. Reperfusion contractile function was improved significantly and lactate dehydrogenase release was reduced by these compounds. Time to contracture was also increased significantly by the (-)-enantiomer (EC25 = 2.27 microM), cromakalim (EC25 = 4.89 microM) and the (+)-enantiomer (EC25 greater than 100 microM). We determined if cromakalim, in a concentration which does not depress cardiac function (10 microM), can preserve high energy phosphates during ischemia in isolated rat hearts. Cromakalim significantly preserved ATP at 15 to 25 min of ischemia. Adenylate energy charge was also significantly improved by cromakalim at 20 to 25 min into an ischemic episode. Thus, the cardioprotective effects of cromakalim are stereoselective and may be due partly to preservation of myocardial energy reserves. It is significant that cromakalim can preserve adenine nucleotides despite its lack of negative inotropic effects.

Adenine Nucleotides↗
PubMed1988

Estimation of the rate constants in a data-sparse environment: comparison of a mathematical method and least squares analysis.

A new method is presented for estimating the rate constants for the one-compartment open model with first-order absorption in a data-sparse environment. It is based on the principles of matrix algebra and system theory and requires only three to four plasma samples drawn at equal time intervals (a minimum of at least one sample in the absorption phase and one sample in the elimination phase). The utility of the technique is illustrated by comparing the parameter estimates from the matrix method with the estimates from a nonlinear computer parameter estimation program. In the preliminary evaluation of the method with both perfect data and data with randomly distributed error, the parameter estimates from the matrix method proved to be as good as the computer estimation for data-sparse systems. In a more realistic comparison with published patient data, the matrix method resulted in 0 to 456% better estimates of kel and ka than the computer estimation. Since the matrix method is mathematically simple and requires only three to four blood samples, it should prove very useful in data-sparse systems (e.g., clinical or small animal situations) where a minimum amount of blood samples can be drawn.

Absorption↗
PubMed1986

Pulmonary arterial changes in patients with ventricular septal defects and severe pulmonary hypertension.

In 25 patients, aged eight months to 31 years, with ventricular septal defect (VSD; isolated in 15, the others with atrial septal defect, PDA, coarctation or patent ductus arteriosus + coarctation), each with severe pulmonary artery hypertension (pulmonary artery systolic pressure [Ppa] at least 75% of systemic and an elevated pulmonary vascular resistance), we related morphologic and morphometric data from open-lung biopsy to hemodynamic measurements obtained at cardiac catheterization during the same hospital admission. Of the hemodynamic features measured, only the ratios of pulmonary-to-systemic flow and pulmonary-to-systemic resistance correlated significantly with structure. Neither pulmonary artery pressure (Ppa) nor pulmonary vascular resistance correlated significantly with any structural feature studied. The increased external diameter of respiratory bronchiolar arteries in those with the more advanced Heath-Edwards grades reflects dilatation and suggests that it is in the small arteries of the distal arterial bed that the changes of pulmonary hypertension are most significant. Neither age nor body weight correlated significantly with the degree of structural or hemodynamic abnormality. In the ten patients who underwent VSD closure, Ppa was measured postoperatively. The Heath-Edwards grade (no more than one grade-III lesion) and arterial density (at least one-half that normal for age) were the best correlates of the difference between preoperative Ppa and Ppa immediately after corrective surgery. The presurgical catheterization data, including pulmonary resistance and the resistance ratio, did not correlate significantly with change in Ppa following VSD closure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1985

Pharmacokinetics of ethynyl estradiol: a current view.

There are large discrepancies in the values reported for the parameters of ethynyl estradiol pharmacokinetics. Economies in sampling frequency (in the hope that computer simulation will serve the purpose), difficulties in measurement of plasma levels resulting from the small doses used, extensive oxidative metabolism, distribution, and enterohepatic circulation all complicate the effort to obtain reliable data. The problems in quantitating various pharmacokinetic parameters and the techniques for their evaluation, as well as methods for the determination of the requisite sampling times and frequencies are discussed, and best estimates for the various parameters, as derived from the literature, are provided.

Biological Availability↗
PubMed1984

Evaluation of the bioavailability of sarpicillin, the methoxymethyl ester of hetacillin, in humans.

The relative bioavailability of sarpicillin (the methoxymethyl ester of hetacillin) from three different oral dosage forms was compared in humans employing a three-way crossover study design. Each unit dose contained 250 mg of sarpicillin in terms of anhydrous ampicillin activity. The comparative bioavailability of a tablet containing added buffer, a liquid-filled capsule, and a standard powder-filled capsule was determined. The bioavailability parameters were Cmax, tmax, and AUC of intact plasma sarpicillin levels and saliva ampicillin levels. Significant correlation was found between plasma sarpicillin levels and saliva ampicillin levels following the administration of sarpicillin. All three formulations yielded statistically similar Cmax and AUC values with respect to plasma sarpicillin and saliva ampicillin levels. However, a more rapid absorption of intact sarpicillin was observed with the buffered tablet formulation, as reflected by significantly smaller tmax for both plasma sarpicillin and saliva ampicillin levels. The faster absorption from the tablet formulation gave more precise absorption among subjects.

Adult↗
PubMed1984

Membrane solubility parameter and in situ release of theophylline.

The solubility of theophylline in polyethylene glycol 400-water binary mixtures was analyzed in terms of solute-solvent interaction using the solubility parameter principle of Hildebrand. Preliminary in situ (rat gut permeation) studies with the solvent mixtures having varying polarity as expressed by the solubility parameter showed that (a) the more alike the solubility parameter of theophylline (delta 2 = 14, as obtained from solubility studies) and the solubility parameter of the solvent mixture, the greater was the attraction of solvent for the drug (b) sufficient similarity must exist between the solubility parameter of theophylline and that of the intestinal mucosa to promote bioabsorption, and (c) from the above, it follows that there exists a competition between solvent and rat gut membrane for the drug. The solubility parameter of the solvent vehicle must be such that it does not impede absorption of the molecules into the intestinal mucosa.

Animals↗
PubMed1983

The pharmacokinetics and metabolism of ethinyl estradiol and its three sulfates in the baboon.

Ethinyl estradiol sulfates are major circulating metabolites of ethinyl estradiol (EE2); this is a relationship analogous to that of endogenous estrone and estrone sulfate. Because of the wide use of contraceptives containing EE2, the pharmacokinetics of its sulfate conjugates are of some importance. In previous studies of the intermediate metabolism of ethinyl estrogens we have shown that the baboon is an appropriate animal model. Accordingly, oral and/or intravenous doses of EE2 or each of its three sulfates were administered to castrate female baboons, and plasma levels of EE2 and its sulfates were studied by specific radioimmunoassay or radioisotope counting. After intravenous administration of EE2, the 3-sulfate and the 3,17-disulfate are the major circulating metabolites. After oral dosage administration, the 3-glucuronide and, in some cases, the 3,17-diglucuronide also become important. After intravenous administration, about twice as much of the drug exists in the sulfate as in the free form, as reflected by the areas under the plasma level curves. The bioavailability of orally administered EE2 was about 60%, confirming the presence of a substantial first-pass effect. Hydrolysis at the 17-position occurs when EE2-17-sulfate is administered orally but appears not to occur with intravenous administration. EE2 and the three sulfates, given intravenously, exhibited two-compartment open-model kinetics. The elimination phase half-lives of all four compounds were similar, ranging from 8.8 to 11.2 hours. The area under the plasma level curve of EE2 resulting from the intravenous administration of the 3-sulfate was approximately 8% of the total area under the plasma level curve of both EE2 and EE2 sulfates. The ratio of the area under the plasma level curve of sulfates resulting from 3-sulfate administration compared to the other two sulfates was approximately 0.3, reflecting the existence of other metabolic pathways for its disposition.

Administration, Oral↗
PubMed1979

High steady-state levels of uric acid produced in rats by dietary training and potassium oxonate.

To reduce the inherent variability in serum uric acid levels of animals allowed ad libitum exposure to food containing potassium oxonate and uric acid, male Sprague-Dawley rats were trained to eat their daily food allotment in a 1.25-hr period each morning. After training the rats were fed a food mixture containing 5% potassium oxonate and 2% uric acid (w/w each). Serum blood levels of uric acid reached a steady state within 2 hr; these levels were maintained for an additional 4 hr. It is believed that the stomach emptying rate is a zero-order process under these experimental conditions.

Animals↗
PubMed1979

A method to predict infinity values for biexponential processes.

An equation is presented which allows infinity values for biexponential processes to be predicted in the early nonlinear phase when samples are taken at equal time intervals. This equation is independent of the value or ratio of the rate constants involved in the process. However, this method is very sensitive to noise normally associated with urine data.

Digoxin↗
PubMed1977

The effect of ion pair formation on the antimuscarinic activity of methantheline.

The quaternary ammonium compound, methantheline, was found to antagonize acetylcholine induced contractions in isolated guinea pig ileum by a mechanism which did not conform to the criteria for either competitive or non-competitive inhibition. Enhancement of the lipid solubility of methantheline by formation of an ion pair with trichloracetate failed to influence its cholinergic inhibitory activity. The results suggest that in the guinea pig ileum a) an intracellular site of action does not exist for methantheline and b) the membrane receptors for methantheline most likely are located in an aqueous environment.

Acetylcholine↗
PubMed1977

In vitro photodecomposition of uric acid in presence of riboflavin II.

In vitro studies on the photodecomposition of uric acid in the presence of the monosodium salt of riboflavin 5'-phosphate in buffers at various pH values, in methanol, and in human plasma are reported. The decomposition rate increased with increasing pH and was independent of solvent or buffer species. The mechanism appears to be an energy transfer process involving triplet riboflavin and single oxygen. Riboflavin-enhanced photodecomposition of uric acid occurred in vitro in hyperuricemic human plasma.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Human pharmacokinetics of ethynyl estradiol 3-sulfate and 17-sulfate.

Pharmacokinetic parameters of ethynyl estradiol 3-sulfate (EE-3) and 17-sulfate (EE-17) were estimated. Each sulfate was administered orally and intravenously to five ovariectomized volunteer women. Blood samples were taken over a period of 24 h. Radioimmunoassay for free and sulfoconjugated ethynyl estradiol (EE) was performed. The analysis of the plasma concentrations obtained after administration of EE-3 and EE-17 indicates significant differences in their pharmacokinetic profiles. EE-3 is cleared more rapidly from the central compartment (systemic circulation), which may indicate that differences in protein binding, tissue binding, metabolism, and distribution exist between EE-3 and EE-17. It has been suggested that these conjugates are a slow-release reservoir for maintenance of blood levels of free EE itself. However, previous studies in baboons have shown that the half-lives of the free and sulfoconjugated EE are similar (ranging from 8.8 to 11.2 h), which is not consistent with this hypothesis. The t1/2 beta (mean 9.28 h) of the 17-sulfate after IV administration was almost identical in women and baboons, and similar to the t1/2 beta of free EE, confirming the previous observation. Only 3.4% of IV and 11.4% of the orally administered 17-sulfate appeared in the blood as free EE; with the 3-sulfate, the conversions were 13.7 and 20.7%, respectively, suggesting that these sulfates are not important slow-release reservoirs. The similarity of pharmacokinetic parameters between women and baboons suggests that this species of nonhuman primate is, in important respects, a suitable animal model for clinical pharmacology.

Administration, Oral↗