Search PubMed⌕ Search

Biomedical subjects

P J Shea

Publications and source records attributed to P J Shea.

At least 19 recordsLinked to original sources
PubMed2002

Catalytic oxidation of TNT by activated carbon.

Activated carbon can remove 2,4,6-trinitrotoluene (TNT) and 1,3,5-trinitrobenzene (TNB) from aqueous solution and promote oxidation of TNT. After equilibrating a 0.35 mM TNT solution with activated carbon (0.2-1% w/v), HPLC and GC/MS analysis confirmed the presence of 2,4,6-trinitrobenzaldehyde (TNBAld) and 2,4,6-trinitrobenzene (TNB), and provided strong evidence supporting 2,4,6-trinitrobenzyl alcohol (TNBAlc) as an intermediate of TNT oxidation. After 6 d, TNT and its oxidation products were strongly bound to the activated carbon, while TNB was extractable with acetonitrile. Observations indicate that activated carbon catalyzes TNT oxidation to TNBAlc, which is readily oxidized to TNBAld and TNB in the absence of activated carbon under dark conditions. While adsorbed TNB was extractable with acetonitrile, activated carbon promoted rapid TNT oxidation and formation of unextractable residues. Strong binding is attributed to catalyzed oxidation of the TNT methyl group, probably through a free radical mechanism, and subsequent chemisorption of oligomers and polymerized products that are not desorbed from micropores. Our observations indicate TNT oxidation and bound residue formation after sorption by activated carbon increases the effectiveness of activated carbon to decontaminate water.

Adsorption↗
PubMed2001

Potential of activated carbon to decrease 2,4,6-trinitrotoluene toxicity and accelerate soil decontamination.

Activated carbon can be used to decrease 2,4,6-trinitrotoluene (TNT) toxicity and promote bioremediation of highly contaminated soil. Adding activated carbon at 0.25, 0.75, and 1.0% (w/w) to Sharpsburg soil contaminated with 500, 1,000, and 2,000 mg TNT/kg decreased concentrations of TNT and its transformation products in soil solution to 5 mg/L or less, resulting in low toxicity to corn plants (Zea mays L.) and soil microorganisms. As much as 50% of the added TNT was rapidly bound to the soil-activated carbon matrix. Simultaneous accumulation of 2,4,6-trinitrobenzaldehyde (TNBAld) indicated that the activated carbon promoted oxidation of TNT. Some of the TNBAld was further oxidized to 1,3,5-trinitrobenzene, followed by reduction to 3,5-dinitroaniline. Reversibly bound TNT was gradually transformed to 2-amino-4,6-dinitrotoluene and 4-amino-2,6-dinitrotoluene, and both were bound to the soil-activated carbon matrix. The transformation and binding of TNT to soil were further promoted by incorporating shredded corn plants after growing for 52 d in the activated carbon-amended soil. After 120 d, these amendments reduced extractable TNT and transformation products by 91% in soil containing 2,000 mg TNT/kg, compared to 55% in unamended soil. These results demonstrate the potential use of activated carbon in combination with plants to promote in situ bioremediation of soils highly contaminated with explosives.

Carbon↗
PubMed2000

Rapid spectrophotometric determination of 2,4,6-trinitrotoluene in a Pseudomonas enzyme assay.

Although TNT (2,4,6-trinitrotoluene) and its degradation products can be quantified by HPLC, this method is not suitable for simultaneous analyses of the numerous samples typically encountered in enzyme studies. To solve this problem, we developed a simple and rapid spectrophotometric assay for TNT and tested the procedure using partially purified nitroreductase(s) from a Pseudomonas aeruginosa isolate, which transformed TNT in the culture medium. In highly alkaline solution, TNT (pK(a)=11.99) exhibits significant absorbance at 447 nm, while major metabolites, 2-amino-4, 6-dinitrotoluene (2ADNT), 4-amino-2,6-dinitrotoluene (4ADNT), and 2,6-diamino-4-nitrotoluene (2,6DANT) display no absorbance at this wavelength. Assay mixtures of TNT, Tris-HCl buffer, a reductant, and the enzyme(s) were analyzed by measuring absorbance 4 min after adjusting the pH to 12.2. TNT transformation to colorless metabolites was linear with respect to protein and substrate concentrations. Using the assay, we determined that TNT nitroreductase(s) from the isolate required an electron donor and preferred NADH to NADPH. TNT transformation increased when NAD was recycled to NADH using glucose-6-phosphate (GP) and glucose-6-phosphate dehydrogenase (GPDH). Enzymatic transformation of TNT was completely inhibited by Cu(2+) (5 mM) and was partially inhibited by other divalent metallic cations. Because the assay is sensitive to ammonium sulfate, dithiothreitol, ascorbic acid, and sodium phosphate, extracts should be assayed in the absence of these components.

Biodegradation, Environmental↗
PubMed1997

Denitration of 2,4,6-trinitrotoluene by Pseudomonas savastanoi.

Past disposal of wastewaters containing 2,4,6-trinitrotoluene (TNT) at the former Nebraska Ordnance Plant has resulted in numerous acres of TNT-contaminated soil. Examining the microbial population of these soils revealed several TNT-tolerant Pseudomonas spp. We selected one species, P. savastanoi, to determine its ability to transform TNT. Pure culture experiments were performed in pseudomonas minimal medium containing 0.31 mM TNT (70 mg TNT . L(-1)) under varied nutrient and cell density regimes. Experiments with TNT as a sole C or N source showed that P. savastanoi has the ability to denitrate TNT, as evidenced by production of 2,4-dinitrotoluene (2,4-DNT) and NO2- with time. TNT denitration and formation of 2,4-DNT were enhanced by removing NH4+ and adding NO2- to the growth medium. In all experiments, 2-amino-4,6-dinitrotoluene (2-ADNT) and 4-amino-2,6-dinitrotoluene (4-ADNT) appeared as incidental reduction products. Glucose addition to the medium enhanced 2-ADNT and 4-ADNT production and decreased denitration of TNT. Mid-log phase cells rapidly transformed [ring-14C(U)]TNT but were unable to mineralize significant quantities of TNT, as evidenced by conversion of less than 1% of the label to 14CO2. These results indicate that P. savastanoi is a TNT-tolerant pseudomonad that can promote TNT degradation through reductive denitration and nitro moiety reduction.

Aniline Compounds↗
PubMed1994

Mechanical coronary artery shortening with vessel wall deformity during directional coronary atherectomy: first reported case involving the left anterior descending artery.

Coronary spasm, dissection, thrombosis, and mechanical coronary artery obstruction due to vessel shortening and deformity resulting from kinking, invagination, or collapse in an accordion-like fashion are recognized sources of iatrogenic obstruction during PTCA. Rapid recognition is required to initiate appropriate therapy. Described is the first reported case of mechanical obstruction involving the left anterior descending artery.

Aged↗
PubMed1992

Mechanical right coronary artery shortening and vessel wall invagination: a fourth cause of iatrogenic coronary obstruction during coronary angioplasty. A case report and review of the literature.

Coronary spasm, dissection, and localized thrombosis are recognized sources of iatrogenic obstruction during coronary angioplasty. A fourth important cause is reported, namely, guidewire-induced mechanical straightening and shortening of tortuous right coronary artery resulting in the invagination of redundant vascular tissue. Reversal is achieved with guidewire retraction. Recognition of this entity is crucial to avoid unnecessary and potentially harmful intervention.

Aged↗
PubMed1992

Forced-choice versus free-choice procedures: caffeine self-administration in humans.

Methodological comparisons of procedures for drug self-administration are rare. In studies examining the reinforcing effect of caffeine in humans, caffeine self-administration usually has been inferred from performance under forced-choice procedures. In the present experiment, caffeine self-administration via coffee was compared under forced-choice and free-choice conditions; i.e., when subjects were and were not required to use a minimum number of coffees. Ten moderate coffee drinkers (2-7 cups/day) were assigned to forced- and free-choice conditions using a randomized cross-over design. Under each choice condition, subjects completed six independent, double-blind trials, consisting of a 2-day exposure period followed by a 2-day test period. During exposure, subjects consumed either decaffeinated or caffeinated (100 mg/serving) coffee on day 1 and the other coffee on day 2. During the test period, subjects had concurrent access to the same decaffeinated and caffeinated coffees. Under the forced-choice condition, subjects were required to drink at least four cups of coffee per day during the test period. Under the free-choice condition, subjects did not have a minimum-cup requirement. In general, the relative rate at which subjects self-administered caffeinated versus decaffeinated coffee was similar across choice conditions, even though subjects self-administered significantly fewer cups of both coffee types under the free-choice than the forced-choice condition. These results suggest that, at least for caffeine, forced-choice and free-choice procedures produce comparable results. Whether this finding generalizes to a context in which caffeine or another drug is more robustly self-administered, remains to be determined.

Adult↗
PubMed1992

Caffeine drug discrimination in humans: acquisition, specificity and correlation with self-reports.

This study evaluated the discriminative stimulus effects of caffeine in humans. Nine normal male and female volunteers (ages 18-28) were trained to discriminate between the methylxanthine central nervous system stimulant caffeine (320 mg/70 kg, p.o.) and placebo. Monetary reinforcers were earned for identifying correctly the letter code associated with each substance. After four training sessions, the ability to discriminate between the two training conditions was tested for 20 sessions (test-of-acquisition). In subjects who met the criterion for discrimination (i.e., greater than or equal to 85% correct responding on greater than or equal to 4 consecutive sessions during the last 10 test-of-acquisition sessions) dose-effect curves for caffeine (0, 56, 100, 180, 240 and 320 mg/70 kg) and for the benzodiazepine triazolam (0, 0.10, 0.32 and 0.56 mg/70 kg) were determined. Seven of the nine subjects learned the caffeine-placebo discrimination and their performance improved across the 20 test-of-acquisition sessions. The training dose of caffeine (320 mg/70 kg) produced stimulant-like self-reports that differed from placebo when the letter codes were identified correctly, but not when the letter codes were identified incorrectly. Novel caffeine doses produced dose-related increases in caffeine-appropriate responding (N = 4), whereas triazolam produced predominantly placebo-appropriate responding (N = 3) and self-reports that differed from both caffeine and placebo. Throughout dose-effect curve determinations, the training dose of caffeine and placebo continued to be identified correctly (range: 84-100% correct responding). These results suggest that a caffeine (320 mg/70 kg)-placebo discrimination 1) can be acquired and maintained, 2) is related to self-reported drug effects if the training conditions are correctly identified and 3) has some pharmacological specificity.

Adult↗
PubMed1990

Synthesis and cardiotonic activity of novel biimidazoles.

A series of substituted 2,2'-bi-1H-imidazoles and related analogues was synthesized and evaluated for inotropic activity. Structure-activity relationship studies based on a nonclassical bioisosteric approach indicated the necessity of a cyano group on one of the imidazole rings to obtain the desired pharmacological profile. 4(5)-Cyano-2,2'-bi-1H-imidazole (15a) was the most potent inotropic agent in the series. It produced a 25% increase in left ventricular dP/dt at 0.16 mg/kg iv (ED25% = 0.16 mg/kg) and increased left ventricular contractile force 60% at 1 mg/kg iv in anesthetized dogs. Compound 15a is a good inhibitor of type IV cyclic nucleotide phosphodiesterase isolated from dog heart having a potency similar to that of amrinone. Neither 5'-cyano-2,4'-bi-1H-imidazole (44) nor 4-cyano-2,4'-bi-1H-imidazole (48) demonstrated inotropic activity. In addition, the two possible 1,1'-dimethylcyano-2,2'-bi-1H-imidazoles (24 and 25) were inactive, indicating that an acidic NH as well as a cyano group are essential for inotropic activity.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1988

Synthesis and activity of partial retro-inverso modified atrial natriuretic factor analogs.

The synthesis and pharmacological activity of partial retro-inverso modified rat atrial natriuretic factor (rANF) analogs is described. The route to these compounds utilized a combination of solution and solid-phase methods. The analogs prepared all contain a reversed amide bond (psi[NHCO]) at the Ser 25 to Phe26 linkage. This bond has been suggested to play a key role in the metabolic inactivation of ANF. The analogs are of comparable potency to the endogenous peptide rANF1-28 in binding to cultured rat vascular smooth muscle cells, in relaxing serotonin contracted rabbit aortic rings, and as natriuretic/diuretic agents in anesthetized rats. None of the peptides has an extended duration of action in vivo.

Animals↗
PubMed1985

New bicyclic antidepressant agent. Synthesis and activity of napactadine and related compounds.

A number of N,N'-dialkylarylamidines were synthesized and evaluated for antidepressant activity. Several of these compounds were synthesized from the corresponding nitriles by a new method. Slight structural modification in the series caused a marked change in biological activity and led to compounds as active as imipramine. The arylacetamidine, N,N'-dimethyl-2-naphthaleneethanimidamide hydrochloride (33) (napactadine) was selected for clinical study. Forty-eight additional analogues of 33, including a number of N-alkylamidines, were prepared.

Aggression↗
PubMed1981

Toxicity of acephate and methamidophos to dark-eyed juncos.

The calculated, acute oral LD50 of acephate and methamidophos to dark-eyed juncos (Junco hyemalis) was 106 mg/kg and 8 mg/kg, respectively. Brain cholinesterase (ChE) activity in birds that died after acephate poisoning was depressed 80% below that of control birds. Birds that died of acute methamidophos poisoning had brain ChE depression of 60%. The birds killed by acephate had brain acephate residue concentrations greater than 2 mg/kg and methamidophos concentrations usually greater than 0.25 mg/kg. Eighty percent of the birds killed with methamidophos had brain methamidophos concentrations greater than 0.1 mg/kg. The five-day feeding LC50 for acephate was 1485 mg/kg. Brain ChE activities of birds which died early in the study were less depressed (51.5%) than those which died at a later date (69.6%). Brain residues of acephate and methamidophos were lower in these birds than in the birds of the acute oral LD50 studies. Brain ChE activity returned to normal within three days after the birds received a single sublethal dose of acephate. These studies indicate that the amount of acephate needed to produce the ChE depression found in other investigations in most dark-eyed juncos exposed to forest applications of insecticide is about one-fifth of the LD50; however, in a few birds the ChE activity may be depressed to near lethal levels.

Animals↗