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Biomedical subjects

G A Digenis

Publications and source records attributed to G A Digenis.

At least 73 records · Page 4Linked to original sources
PubMed1982

Enhanced entrapment of a quaternary ammonium compound in liposomes by ion-pairing.

The encapsulation of a quaternary ammonium compound by multilamellar liposomes was enhanced by formation of ion-pairs with a counterion. Thus, [14C]methantheline bromide was synthesized and paired with a 25 M excess of trichloroacetate. Under these conditions, the amount of radioactivity entrapped by phosphatidylcholine liposomes was three times greater than when no trichloroacetate was present. The increased liposomal loading was probably due to the solubilization of the ion-pair in the lipid membrane of the liposome.

Chemical Phenomena↗
PubMed1982

Distribution of 13N in rat tissues following intravenous administration of nitroso-labeled BCNU.

The concentrations of label in 16 major organs and tissues of pentobarbital-sedated normal male rats were measured at six time points ranging from 0.2 to 50 min after IV injection of the antitumor drug BCNU labeled in the nitroso position with cyclotron-produced nitrogen-13. Initial (12-s) concentrations in the lungs, kidneys, and heart were 41, 13, and 11 times the whole-body average, respectively. Time for clearance of the first 50% of the injected dose from the circulation was of the order of several seconds. Estimated first-pass extractions of 70% or more were noted in the heart, kidneys, brain, stomach, small intestine, muscle, fat, and bone. Washout of label from the heart and lungs was quite rapid, removing most of the initially extracted 13N from these organs by 2 min after injection. Label concentrations in the kidneys exceeded those in all other tissues studied between 2 and 50 min. Secondary accumulations of 13N were observed in muscle, skin, liver, small intestine, and fat. Label concentrations in a number of tissues closely paralleled the steadily decreasing concentration in blood for various intervals between 5 and 50 min. The results suggest that the toxic insult to lung tissue from IV administered BCNU is effected in a period of several minutes. They also suggest that intra-arterial administration of the drug would significantly raise the target/non-target dose ratio and lower the incidence of pulmonary toxicity.

Animals↗
PubMed1981

Tissue distribution studies of [18F]haloperidol, [18F]-beta-(4-fluorobenzoyl)propionic acid, and [82Br]bromperidol by external scintigraphy.

Tissue distribution studies of [18F]haloperidol and [82Br]bromperidol, two potent neuroleptic drugs, were performed in rats by serial sacrifice. The usefulness of external scintigraphy in obtaining tissue distribution data in large animals is demonstrated by the tissue distribution of [18F]haloperidol in rhesus monkeys. Both serial sacrifice and external scintigraphic studies demonstrated that uptake of the two drugs after intravenous administration into their target organ, the brain, was very fast and that the ratio of brain to blood levels was high throughout the 2-hr observation. Bromperidol appeared to reach peak brain levels faster than its chloro analog, haloperidol. Both bromperidol and haloperidol concentrated overwhelmingly in the rat lung. Haloperidol also showed a high affinity for the monkey lung. The disposition pattern in rats of [18F]-beta-(4-fluorobenzoyl)propionic acid, an apparent intermediate in butyrophenone metabolism, was entirely different from that of the parent drugs. This metabolite did not concentrate in the rat brain.

Animals↗
PubMed1981

Noninvasive dissolution measurement using perturbed angular correlation.

A novel noninvasive technique was developed to measure dissolution of the water-soluble component of a solid dosage form using indium 111 and perturbed angular correlation. The method involves time-delayed coincidence counting of two cascading gamma-rays that exhibit angular correlation. This angular correlation can be perturbed if the intermediate excited state of the nucleus is reoriented due to an interaction with its environment. When such an interaction occurs, as in a phase change (solid to liquid), the perturbation changes can be shown by anisotropy. A highly perturbed condition in the solid state results in low values (0.02-0.04), while increasing values of anisotropy indicate dissolution. Anisotropy values reach 0.14-0.15 when the total unperturbed physical state (liquid) exists. The worth of this technique was demonstrated by both in vitro and in vivo determinations of dissolution rates.

Gamma Rays↗
PubMed1980

Rate and pattern of gastric emptying in humans using 99mTc-labeled triethylenetetraamine-polystyrene resin.

The preparation and application of a new radiopharmaceutical used in the investigation of the rate and pattern of gastric emptying by external scintigraphy are described. Triethylenetetraamine was bound covalently to cross-linked chloromethylated polystyrene. The triethylenetetraamine-polystyrene resin tenaciously and rapidly bound technetium 99m. The gastric emptying rate was evaluated in normal adult volunteers and patients by serially recording the gastric radioactivity after ingestion of a test meal mixed with 99mTc-labeled triethylenetetraamine-polystyrene resin. The data indicated that 99mTc-labeled triethylenetetraamine-polystyrene resin was an ideal agent for assessing the rate and pattern of gastric emptying in humans. The gastric emptying half-time (t 1/2 GE) in normal subjects ranged from 25 to 75 min.

Ethylenediamines↗
PubMed1980

Synthesis of [82Br]bromperidol and preliminary tissue distribution studies in the rat.

A procedure is described for the preparation of [82Br]bromperidol with specific activity 440 muCi/mg. The incorporation of bromine-82 into the molecule was accomplished through Brackman and Smit's modification of the Sandmeyer reaction, during the last step of the synthetic route. This involved the formation of a complex between Cu82Br2 and nitric oxide gas in acetonitrile, which was then allowed to react with 4-[4-(aminophenyl)-4-hydroxy-piperidinyl]-1-(4-fluorophenyl)-1-butanone (aminoperidol, 10) to give [82Br]bromperidol in about 1.5 h. Cupric 82Br]bromide was prepared in situ from K82Br and CuSO4.5H2O. The radiochemical and chemical yields for the preparation of [82Br]bromperidol from K82Br were 10.4 and 12%, respectively. Preliminary tissue distribution studies with the labeled bromperidol in the rat showed that the uptake of radioactivity by the liver, brain, kidneys, and the lungs was very fast and was in the declining phase in the latter organs 15 min after iv administration.

Animals↗
PubMed1977

Carbon-13 nuclear magnetic resonance investigations into the interactions of bisulfite with pyrimidine nucleosides and nucleotides.

Carbon-13 NMR is utilized to demonstrate the attack of bisulfite anion on uridine, 5-fluorouridine, and uridine 5'-monophosphate. The attack produces a pair of diastereomeric adducts similar in structure to those seen in the uracil series. Intensity data from the equilibrium system give an estimate for the individual equilibrium constants. Thymidine and thymidine 5'-monophosphate show no evidence of nucleophilic attack by bisulfite. This evidence indicates that bisulfite addition to nucleosides and nucleotides models the enzymatic methylation of uridine by the enzyme thymidylate synthetase better than the uracil bisulfite system.

Chemical Phenomena↗
PubMed1977

Stable and short-lived isotopes in the study of tissue distribution.

Two relatively novel techniques that are utilized in the study of tissue distribution of drugs are discussed. The first technique, GC-MS fragmentography, provides an opportunity for the identification and quantification of several compounds and internal standards, in the same analysis, at picogram to nanogram amounts. The second technique utilizes short-lived radioisotopes and external scintigraphy. This approach can continuously monitor the tissue and organ distribution of an appropriately labeled compound. It produces quantifiable results and provides an opportunity for doing several experiments on the same animal in a noninvasive manner.

Animals↗
PubMed1976

Anaerobic photodecomposition of an acridan drug through energy transfer.

Anaerobic irradiation of 2-chloro-9-(3-dimethylaminopropyl)acridan phosphate (1:1) (IIIa) with filtered visible light (300-400 nm) resulted in its quantitative conversion to its acridine derivative IV. Photoproduct IV exerted significant product catalysis on the reaction rate at concentrations of 5 x 10(-6) M. The anaerobic photodecomposition of IIIa to IV was catalyzed by the monosodium salt of riboflavin 5-phosphate (Ia). Loss of Ia was insignificant relative to that of IIIa, and reagents known to serve as quenchers of the triplet state of Ia retarded the reaction. Fluorescence spectra of Ia in the presence of IIIa and 1 x 10(-4) M KI indicated no quenching of the Ia singlet excited state. No deuterium isotope effect was noticed when IIIa and its deuterated derivative IIIb were subjected to anaerobic photodecomposition in the presence of Ia. It is suggested that the anaerobic photodecomposition of IIIa by visible light in the presence of Ia proceeds via a triplet-triplet energy transfer from Ia to IIIa.

Acridines↗