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G A Digenis

Publications and source records attributed to G A Digenis.

At least 55 records · Page 3Linked to original sources
PubMed1988

Development of an HPLC assay for the analysis of tetrafluoroputrescine--a putrescine analog.

A simple reverse-phase liquid chromatographic system with ultraviolet detection at 254 nm for tetrafluoroputrescine (TFP), a putrescine analog, is described. The assay involves precolumn derivatization of TFP with dansyl chloride at pH 6.8-7.5 at 60 degrees C, followed by separation from putrescine (PUT) and quantitation. The derivatization procedure was adapted for the simultaneous analysis of TFP and PUT in whole blood components. Also, preliminary studies on protein binding of TFP are reported.

Animals↗
PubMed1988

Disposition of [14C]nonoxynol-9 after intravenous or vaginal administration to female Sprague-Dawley rats.

The disposition of nonoxynol-9 labeled with carbon-14 at the ethylene oxide units was studied following an iv or vaginal administration to female Sprague-Dawley rats. The results from the vaginal administration studies indicate 12.8% absorption of 14C radioactivity in 6.0 hr and 37.7% in 24.0 hr. Tissue distribution studies showed that the small and large intestines, including their contents, had the highest 14C activity by either route of administration. Radiomonitored HPLC of bile collected at 6.0 hr and urine at 6.0, 24.0, and 48.0 hr following an iv injection of [14C]nonoxynol-9 showed that the compound was completely metabolized in the body of the rat. The metabolites were primarily excreted in the feces and secondarily in the urine. Analysis of urinary metabolites containing the carbon-14 label, 6.0 hr following an iv dose, indicated the presence of highly polar neutral (53.27%) and acidic (39.23%) species.

Administration, Intravaginal↗
PubMed1987

Tc-99m labeled triethelene tetraamine polysterene resin gastric emptying studies in bulimia patients.

To evaluate gastric emptying in patients with bulimia, 20 patients (all women, ranging in age from 12 to 49 years) with upper gastrointestinal symptoms ingested 150-200 microCi 99mTc-triethelene tetraamine polysterene resin in cereal and had scintigraphy in the supine position. Data were accumulated at 5 min intervals to determine the gastric emptying time (GET). The results showed that the gastric emptying time was prolonged in 12 patients and decreased in 8. All 12 patients with prolonged emptying time were given 10 mg metoclopramide intravenously; 9 of these had a good response and 3 had no response. Although all patients had subjective symptoms of gastric dysfunction, the results indicate that about 60% had delayed and 40% had rapid gastric emptying. The findings of two extremes of gastric emptying time remain to be explained, however, this enables (a) objective documentation of gastric emptying as this technique (b) can separate those patients with rapid GET from those with prolonged GET, who might benefit from metoclopramide.

Adolescent↗
PubMed1987

Disposition of [14C]povidone after oral administration to the rat.

The tissue distribution and excretion of 14C-labelled povidone (polyvinylpyrrolidone; K-30; average mol wt 40,000) was studied in male Sprague-Dawley rats given a single oral dose. The major pathway of elimination of radioactivity was in the faeces, in which 90.8% of the administered dose was recovered after 12 hr and 98.4% after 48 hr. Amounts of radioactivity in major tissues and in the blood were not significantly different from those in untreated controls. A minor amount of radioactivity, representing 0.04% of the administered dose, was detected in the urine after 6 hr. Dialysis studies of [14C]povidone suggested that the absorbed species was a low-molecular-weight (less than 3500) oligomer. It was concluded that an oral dose of [14C]povidone is not significantly absorbed in the rat.

Administration, Oral↗
PubMed1987

Influence of tablet dissolution on furosemide bioavailability: a bioequivalence study.

In order to evaluate the in vitro dissolution and in vivo bioavailability relationship for furosemide, a bioequivalence study was carried out. Furosemide (40 mg) was administered orally to 12 normal volunteers in a 6 x 6 crossover design using six products (five tablets and one solution) obtained from three pharmaceutical companies. Plasma and urine concentrations of furosemide were quantitated by high-performance liquid chromatography (HPLC). Plasma furosemide profiles were analyzed by non-compartmental methods. Compared to the oral solution, all of the formulations exhibited lower peak furosemide concentrations, longer mean residence times, and, in some cases, diminished bioavailability (range, 66-96%). Similar results were obtained when the reference product (a rapidly dissolving tablet) was used as the standard. All of the products failed the 75/75 rule when compared to either reference standard, apparently because of large intersubject variability. The total amount of furosemide excreted in urine could be associated with the percentage drug dissolved (in vitro) at 30 min. The pH 5.6 dissolution medium (compared to pH 4.6) appears to be an appropriate test medium for assuring batch uniformity and bioequivalence of furosemide products.

Administration, Oral↗
PubMed1987

Radionuclide gastric emptying studies in patients with anorexia nervosa.

To evaluate gastric emptying in anorexia nervosa patients, 26 patients (17 females, two males, ranging in age from 13 to 40 yr) with upper GI symptoms ingested 150-200 microCi [99mTc]triethelenetetraamine polysterene resin in cereal and were imaged in the supine position. Data were accumulated at 5 min intervals to obtain the gastric emptying time (GET). The results of the studies were divided into three categories: prolonged, 13 patients; rapid, 11; and normal 3. Twelve of 13 patients with prolonged GET were given 10 mg metoclopramide i.v. injections; nine of the 12 patients had a good response and three had no response. Five of the nine patients underwent metoclopramide therapy and four of the patients showed benefit from the therapy. One patient discontinued metoclopramide therapy because of somnolence. Although all patients had subjective symptoms of gastric dysfunction, our results indicated only 50% had objectively prolonged GET, and another 50% showed normal or even rapid GET. Therefore, this radionuclide study enables quantitatively objective documentation of gastric emptying, separation of those patients with rapid or normal GET from those with prolonged GET, thereby avoiding the possible side effects from metoclopramide medication, and prediction of effectiveness of metoclopramide therapy in patients with prolonged GET.

Adolescent↗
PubMed1986

Retrograde spreading of hydrocortisone enema in inflammatory bowel disease.

A hydrocortisone suspension enema was radiolabeled with [99mTc]technetium sulfur colloid and administered to four normal subjects and eight patients with varying degrees of inflammatory bowel disease. The extent of enema spreading was monitored using external scintigraphy for a period of up to 4 hr after administration. Pretreatment of normal subjects with an evacuation enema resulted in spreading of the radiolabeled enema throughout the entire colon. In seven of the eight patients studied, the enema migrated a distance equal to or greater than the extent of disease involvement. An in vivo stability study with an indium-111-labeled enema, using the perturbed angular correlation technique, revealed that the enema retains its stability for up to 90 min after administration. These results indicate that the use of hydrocortisone enemas may not be restricted to distal bowel disease, but may also be effective in inflammatory bowel diseases involving proximal regions of the colon.

Colitis, Ulcerative↗
PubMed1986

Peptidyl carbamates incorporating amino acid isosteres as novel elastase inhibitors.

The design and synthesis of 13 novel peptidyl carbamates are described. When tested for inhibitory activity toward porcine pancreatic elastase, trypsin, and chymotrypsin, six compounds were found to specifically inhibit elastase without affecting the other two serine proteases. All the active inhibitors had an amino acid isostere at the P1 position. Kinetic studies indicated that the inhibition was competitive with Ki values ranging from 4.23 X 10(-5) to 2.4 X 10(-6) M. The degree of inhibition was found to be dependent on the specificity of the peptide chain for the extended subsites on the enzyme as well as on the nature of P1'. Preliminary work on one inhibitor indicates that the inhibition is reversible and proceeds via the rapid formation of a strong enzyme-inhibitor complex, followed by slow acylation of the serine residue on the active site of the enzyme. Peptidyl carbamates represent a novel class of elastase inhibitors.

Animals↗
PubMed1985

Assessment of antiprotease activity of some carbamate derivatives.

Six carbamate derivatives were tested for inhibitory activity towards porcine pancreatic elastase, trypsin, and chymotrypsin. Only three esters that are isatoic anhydride derivatives were found to inhibit elastase competitively but nonspecifically. KI values for the best two inhibitors were determined from Dixon plots.

Animals↗
PubMed1985

Disposition of radiolabelled suppositories in humans.

The disposition of Witepsol H 15 suppositories radiolabelled with [99mTc] technetium hydroxymethyldiphosphonate was studied after rectal administration in volunteers. The migration of the radiolabel was monitored continuously by external scintigraphy. The resulting scintiphotos were superimposed on lower GI radiographs to determine the extent of spreading of the dosage form in the rectum. The dosage form migrated approximately 5-7 cm into the rectum in nearly all of the studies and was, in general, confined to the lower and middle regions of the rectum. Since the venous supply to the lower rectum leads primarily to the inferior vena cava, the data presented here indicate that the metabolism of drugs sensitive to the 'first-pass' effect may be partially avoided by their rectal administration.

Adult↗
PubMed1984

Peptidyl carbamate esters: a new class of specific elastase inhibitors.

A series of tripeptide carbamate esters were synthesized and tested for inhibitory activity towards porcine pancreatic elastase, trypsin and chymotrypsin. Two of these compounds specifically inhibited elastase [Ki = 4.25 x 10(-5)M and 3.00 x 10(-5)M], and exhibited no effect toward the other two serine proteases. These active tripeptidyl carbamates represent a novel class of specific elastase inhibitors.

Animals↗
PubMed1984

Labeling suspended aerosol particles with short-lived radionuclides for determination of particle deposition.

Radiotracer techniques were developed to examine parameters that characterize pressurized aerosols designed to deliver insoluble particles suspended in the aerosol formulation. Microaggregated bovine serum albumin microspheres that were to be suspended were labeled with iodine-131 (t1/2 = 8 d). This iodination procedure (greater than 80% effective) is also applicable to iodine-123, which possesses superior characteristics for external imaging and further in vivo studies. This report shows that for pressurized aerosols containing suspended particles, each metered dose is approximately equal (not including the priming doses and the emptying doses). Increase in the delivery of the albumin particles out of the canister was best achieved by pretreating the valve assembly with a solution of 2% (w/v) bovine serum albumin in phosphate buffer. Use of a cascade impactor delineated the particle size distribution of the micropheres, with the majority of particles ranging in size from 2 to 8 microns. The data disclosed here indicate that the techniques developed with short-lived radionuclides can be used to quantitate each metered dose, characterize the particle size distribution profile of the aerosol contents, and determine the extent of deposition of the particles in the aerosol canister and all of its components.

Aerosols↗
PubMed1984

Disposition of N-vinyl-2-pyrrolidinone in the rat.

The disposition of N-[14C-vinyl]-2-pyrrolidinone was studied in male Sprague-Dawley rats following a single iv injection. Plasma levels of the intact compound dropped rapidly within the first 6 hours after dosing with a half life of 1.90 hours. Urinary excretion by 12 hours represented 74.9% of a 5 microCi dose while 18.7% was excreted into the bile by 6 hours. 14C-activity attributed to the intact compound was found to be less than 0.59% of the dose in the urine and less than 0.46% in the bile. Tissue distribution studies showed that the liver and small intestines and contents contained the highest accumulation of 14C-activity up to 6 hours after administration of N-[14C-vinyl]-2-pyrrolidinone. Urine analyses performed for metabolite elucidation indicated that 12% of the radioactivity dosed was incorporated into acetate and the major remaining portion in species which appeared to be water soluble acidic compounds.

Animals↗
PubMed1984

Stimulating effects of inosine, uridine and glutamine on the tissue distribution of radioactive D-leucine in tumor bearing mice.

This experiment was carried out in search for stimulators of the in vivo uptake of D- and L-leucine by tumor and pancreas for the possible application to gamma-emitter labeled amino acids in nuclear medical diagnosis. Inosine, uridine, and glutamine which are stimulators of the in vitro incorporation of radioactive L-amino acids into some tumor cells significantly enhanced the uptake of D-leucine into the pancreas, while in Ehrlich solid tumor only a little if any increase was observed. Of the compounds tested inosine showed the highest stimulation of pancreas uptake in the range of doses used, resulting in the best pancreas-to-liver concentration ratio, a factor of significant consideration for pancreas imaging. The uptake of L-leucine by the tumor and pancreas was little affected by these compounds.

Animals↗
PubMed1984

Biological evaluation of radiolabeled D-methionine as a parent compound in potential nuclear imaging.

Based on the high radioactivity uptake of some 14C-labeled D-amino acids in tumors and pancreas of mice, this investigation was undertaken to ascertain possible usefulness of radioactive D-methionine as a nuclear imaging agent. Radioactivity derived from D-[3,4-14C]-methionine in Ehrlich solid tumor was approximately three times higher than that from the L-isomer, but was the same as for mouse pancreas. Excretion rate of the radioactivity of D-[14C]-methionine into urine was approximately two times faster than that of the L-isomer. As compared with two potential imaging agents, 1-aminocyclopentane-1-carboxylic acid and alpha-aminoisobutyric acid, D-methionine showed almost the same radioactivity biodistribution in tumor and pancreas. These results suggest potential for D-methionine as a mother compound for use in tumor and pancreas imaging.

Animals↗
PubMed1983

Tumor selective enhancement of radioactivity uptake in mice treated with alpha-difluoromethylornithine prior to administration of 14C-putrescine.

A group of EMT6 tumor bearing male BALB/c mice which had been treated with alpha-difluoromethylornithine (DFMO, a specific, irreversible inhibitor of ornithine decarboxylase, the enzyme which catalyzes the biosynthesis of putrescine), 8 mg/mouse, ip, 20 and 5 hrs before the 14C-putrescine dose, and a group of control animals were administered 14C-putrescine (0.5 muCi, 0.1 mCi/mmol, iv) 60 min prior to sacrifice. Radioactivity uptake data was obtained for the tumor and 13 major normal organs. In the control animals the tumor exhibited one of the highest uptakes of radioactivity. For DFMO-pretreated mice the radioactivity distribution among most of the normal tissues was not very different from that obtained for the control animals. However, the uptake into the tumor was enhanced by a factor of approximately 4. So, high tumor-to-tissue ratios (3.8, lung to 38, brain) were attained as a result of DFMO treatment.

Animals↗