Robert Gerard Kelly

Determination of C14 and H3 in biological samples by Schöniger combustion and liquid scintillation techniques

Summary The Schoniger combustion technique has been adapted for the preparation of biological samples containing tritium and carbon-14 for liquid scintillation counting. A combustible sample holder made of dialysis tubing permits the efficient drying of biological tissues and homogenates prior to combustion. Following combustion, carbon dioxide is absorbed in a Hyamine hydroxide solution which is then dissolved in a toluene phosphor. Tritiated water is collected as ice which is dissolved in a toluene-ethanol phosphor. A recovery of 96 ± 6% was obtained for a series of 25 determinations of carbon-14 added to various biological samples. A similar experiment involving 30 determinations of added tritium gave results of 96 ± 5% recovery. The method is simple and employs inexpensive and readily available apparatus (Fig. 2). In our experience 50 determinations can be carried out by one individual in an 8-hr period.

Pharmacokinetic studies on minocycline in man

Minocycline, a new member of the tetracycline series, has been reported to have a high level of activity against tetracycline‐sensitive organisms and significant activity against tetracycline‐resistant staphylococci. Results presented show that in man it has a biologic half‐life apprOXimately that of doxycycline but appreciably longer than that of other tetracyclines. It appears to be more rapidly absorbed than doxycycline, demethylchlortetracycline, and methacycline. Evidence indicates that with minocycline, like doxycycline, but unlike other tetracycline antibiotics, absorption following oral administration is essentially complete. Lower values for renal clearance are found for minocycline than for the other tetracyclines studied. Of the minocycline recovered, a higher percentage was excreted in the feces and biologic transformation was greater than with the other tetracyclines. Minocycline has greater lipophilic properties than other tetracyclines, which may account for the highly favorable ratios of tissue to serum concentrations.

A fluorometric method of analysis for tetracycline

Abstract A new method of analysis for low concentrations of tetracycline in biological samples is described. The method is dependent upon the extraction of anhydrotetracycline from an acid-treated protein-free filtrate. The anhydrotetracycline, in a chloroform extract, is then treated with ethanolic aluminum chloride to form a highly fluorescent chelate. The procedure described is compared with accepted analytical procedures for tetracycline (microbiological, radiological) in an experiment in which serum concentrations of the antibiotic were determined at various times (hours) following intravenous administration in dogs.

Studies on the inhibition of histidine decarboxylase, aromatic-l-amino acid decarboxylase and acid secretion by brocresine and its metabolites

Abstract Brocresine (NSD 1055) is rapidly metabolized in vivo. The probable metabolites are 4-bromo-3-hydroxy-benzyl alcohol, 4-bromo-3-hydroxy-benzoic acid and 4-bromo-3-hydroxy-hippuric acid. Brocresine and these metabolites inhibit both rat fetal and rat gastric histidine decarboxylase ( l -histidine carboxylase, EC 4.1.1.22) in vitro with a molar I50 of about 10−8, 10−4, lO−3 and 10−5, respectively, for both enzymes. Brocresine and the metabolites also inhibit aromatic- l -amino acid decarboxylase (3,4-dihydroxy- l -phenylalanine carboxylase EC 4.1.1.26) from hog kidney and rat gastric mucosa in vitro with a molar I50 of about 10−7, 10−4, 10−3 and 10−3, respectively, for both enzymes. Brocresine, the alcohol metabolite and the acid metabolite inhibited rat gastric histidine decarboxylase after intraperitoneal administration of 200 mg kg , whereas the hippurate was only weakly inhibitory. All four compounds inhibited gastric acid secretion in the pylorus-ligated rat, but the acid and hippurate were only moderately inhibitory. The reaction of hemoglobin with brocresine to form methemoglobin readily explains the rapid disappearance of the inhibitory activity of the drug.

Determination of tritium and C-14 in biological samples by rapid combustion techniques.

An important factor contributing to the increased use of tritium, and C14 as well, has been the availability of reliable and convenientto-operate commercial equipment that measures radioactivity by the liquid scintillation technique. This technique offers advantages of simplicity, sensitivity, and routine use that cannot be matched by alternative methods. However, inherent in liquid scintillation technique are two difficulties which make direct application to biological samples impractical. First, organic solvents are necessary for liquid scintillation counting. These are often immiscible with aqueous biological systems and are poor solvents for the polar constituents of biological samples. Second, liquid scintillation technique requires a relatively colorless sample so that the light resulting from the interaction of the beta particle with the phosphor in solution may reach the phototube. Any absorption of light manifests itself as a quenching, thus resulting in lowered counting efficiency.

Bioavailability of sustained release acetazolamide

In this study, we found significant increases in time to arrhythmia in the treatments with amperozide, melperone and bretylium compared with saline, indicating an antiarrhythmic effect of approximately the same magnitude by the doses used in guinea-pigs against digoxininduced arrhythmias. These drugs share class I11 antiarrhythmic properties. As for the treatments with thioridazine and lignocaine the time to arrhythmia was increased but did not reach statistical significance. The results of the present in-vivo study are in agreement with the recent findings (Arlock, unpublished observations) that amperozide has antiarrhythmic properties, and thus warrants further investigation in other models.