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Biomedical subjects

C F Shen

Publications and source records attributed to C F Shen.

11 recordsLinked to original sources

Explosive biodegradation in soil slurry batch reactors amended with exogenous microorganisms.

The present study explores the feasibility of biotreatment of 2,4,6-trinitrotoluene (TNT) and hexahydro-1,3,5-trinitro- 1,3,5-triazine (RDX)-contaminated soils in slurry batch reactors. Radiorespirometric assays showed that anaerobic sludge was able to mineralize 59% RDX to CO2 although significant mineralization of TNT was not observed in all cases. TNT and RDX at concentrations higher than 50 and 100 mg/L respectively were inhibitory to methanogenesis (used as a bioindicator), however, methanogenesis recovered after TNT was transformed into less toxic triaminotoluene. Bioslurry batch reactors containing 40% of contaminated soil (2000 mg RDX and 1000 mg TNT/kg dry soil) were operated under various conditions. Both TNT and RDX were persistent to soil indigenous microbes. Degradation of both TNT and RDX was enhanced by the municipal sludge amendment, although degradation of RDX was only achieved under anaerobic conditions.

Aerobiosis↗

Origin of p-cresol in the anaerobic degradation of trinitrotoluene.

p-Cresol was repeatedly detected as a trace metabolite in anaerobic slurry reactors treating 2,4,6-trinitrotoluene (TNT)-contaminated soils. This study shows that p-cresol was not a metabolite of the anaerobic degradation of TNT, by using a combination of analytical techniques and 13C-labelled TNT. Instead, p-cresol, an intermediate in the degradation pathway of some amino acids, was shown to be inhibited by TNT and its metabolites. The range and persistence of inhibition to p-cresol microbial degradation decreased with the level of amino-substitution of the derivatives. This explains why p-cresol accumulated within the TNT-treating anaerobic bioslurry, as it could not be further biodegraded in the presence of TNT.

Anaerobiosis↗

Monitoring methanotrophic bacteria in hybrid anaerobic-aerobic reactors with PCR and a catabolic gene probe.

We attempted to mimic in small upflow anaerobic sludge bed (UASB) bioreactors the metabolic association found in nature between methanogens and methanotrophs. UASB bioreactors were inoculated with pure cultures of methanotrophs, and the bioreactors were operated by using continuous low-level oxygenation in order to favor growth and/or survival of methanotrophs. Unlike the reactors in other similar studies, the hybrid anaerobic-aerobic bioreactors which we used were operated synchronously, not sequentially. Here, emphasis was placed on monitoring various methanotrophic populations by using classical methods and also a PCR amplification assay based on the mmoX gene fragment of the soluble methane monooxygenase (sMMO). The following results were obtained: (i) under the conditions used, Methylosinus sporium appeared to survive better than Methylosinus trichosporium; (ii) the PCR method which we used could detect as few as about 2,000 sMMO gene-containing methanotrophs per g (wet weight) of granular sludge; (iii) inoculation of the bioreactors with pure cultures of methanotrophs contributed greatly to increases in the sMMO-containing population (although the sMMO-containing population decreased gradually with time, at the end of an experiment it was always at least 2 logs larger than the initial population before inoculation); (iv) in general, there was a good correlation between populations with the sMMO gene and populations that exhibited sMMO activity; and (v) inoculation with sMMO-positive cultures helped increase significantly the proportion of sMMO-positive methanotrophs in reactors, even after several weeks of operation under various regimes. At some point, anaerobic-aerobic bioreactors like those described here might be used for biodegradation of various chlorinated pollutants.

Aerobiosis↗

Susceptibility of stromelysin 1-deficient mice to collagen-induced arthritis and cartilage destruction.

OBJECTIVE: It has long been proposed that stromelysin is one of the major degradative matrix metalloproteinases responsible for the loss of cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA). This hypothesis was tested by examining the arthritic paws of stromelysin 1 (SLN1)-deficient mice for loss of cartilage and for generation of neoepitopes that would be indicative of aggrecan cleavage. METHODS: The SLN1 gene was inactivated in murine embryonic stem cells, and knockout mice deficient in SLN1 activity were bred onto the B10.RIII background. The incidence and severity of collagen-induced arthritis (CIA) were compared in wild-type and knockout mice. Paws from mice with CIA were examined for loss of cartilage and for proteoglycan staining, as well as for the generation of the neoepitope FVDIPEN341. RESULTS: SLN1-deficient mice developed CIA, as did the wild-type N2 mice. Histologic analyses demonstrated no significant differences among the B10.RIII, wild-type, and knockout mice in loss of articular cartilage and proteoglycan staining. No decrease in the FVDIPEN341 epitope was observed in the SLN1-deficient mice. CONCLUSION: Disruption of the SLN1 gene neither prevents nor reduces the cartilage destruction associated with CIA. Moreover, SLN1 depletion does not prevent the cleavage of the aggrecan Asn341-Phe342 bond.

Animals↗

Robust and bootstrap testing procedures for bioequivalence.

A common problem encountered in bioequivalence studies is the presence of outliers. In this situation, the two one-sided t-tests proposed by Schuirmann fail to provide reasonable power for concluding bioequivalence. In contrast, our proposed 2 beta trimmed-t procedure has the following advantages: (1) it has higher efficiency for nonnormal symmetric distributions, (2) it is resistant to outliers, and (3) it is relatively easy to compute. Two bootstrap procedures introduced here provide further justification for the proposed trimmed t-test procedure. Results from Monte Carlo studies illustrate the power of the proposed procedures under various distributional assumptions for a 2 x 2 crossover trial.

Biological Availability↗

Centrally acting drugs act as conditioned stimuli in a conditioned suppression of drinking task.

An experiment was conducted to test whether centrally acting drugs could act as conditioned stimuli (CS) in a classical conditioning paradigm in which electric shock acted as the unconditioned stimulus (US) and suppression of drinking was used as an indicator of a conditioned response (CR). Thirsty rats were allowed to drink water during daily classical conditioning sessions which took place in their home cages. The CS was either a drug injected before the session or a "cocktail" of sensory stimuli (light + tone + vibration) turned on at the beginning of the session. Part way through some sessions the animals received electric foot shock as the US. Two different drugs and the sensory cocktail were used as CSs in a discriminated classical conditioning paradigm in which one drug or stimulus (the CS+) predicted the subsequent occurrence of shock, and the other two conditions acted as CS- stimuli and predicted absence of shock. After an average of 5.7 pairings of the CS+ with shock, conditioned suppression of drinking was observed; the CR occurred only during tests preceded by the CS+ drug or stimulus. At one time or another during the experiment, pentobarbital, phencyclidine, morphine, and pentylenetetrazol were employed as the CS+. Each acquired the ability to elicit a CR, although pentobarbital was noticeably less effective than the other three drugs. All conditioning trials took place in hanging metal cages, but the CR generalized into plastic cages with sawdust floors. Each rat received three successive phases of conditioning with a different CS+ condition employed in each phase; each phase of conditioning was followed by extinction of the CR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Discriminable effects of phencyclidine analogs evaluated by multiple drug (PCP versus OTHER) discrimination training.

This study tested structural analogs of phencyclidine (PCP) using drug discrimination procedures to determine which analogs produced discriminable effects similar to those of PCP. It also tested the utility of multiple-drug discrimination training (PCP versus other drugs or saline) as a method for increasing the specificity produced by training. All discrimination training took place in two-lever operant compartments using FR-10 reinforcement of presses on the correct lever. During training, rats were required to concurrently discriminate PCP from one or more other drug conditions. Rats in group 1 discriminated PCP (lever 1) versus saline (lever 2). Rats in group 2 discriminated PCP (lever 1) versus saline, fentanyl, phenobarbital, amphetamine, or mescaline (lever 2). In both groups 1 and 2, the required discriminations were rapidly learned. The percentage of PCP choices and the ED50 doses obtained during tests for generalization did not differ significantly in groups 1 and 2. Drugs to which responding on the PCP lever generalized included 1-[1-(2-thienyl)cyclohexyl]piperidine, N-ethyl-1-phenylcyclohexylamine, 1-phenylcyclohexylamine, ketamine, 1-(1-phenylcyclohexyl)morpholine, 1-[1-(2-thienyl)cyclohexyl]morpholine, N,N-diethyl-1-phenylcyclohexylamine, N-(iso-propyl)-1-phenylcyclohexylamine, N-methyl-1-phenylcyclohexylamine, N-(n-propyl)-1-phenylcyclohexylamine, Dextrorphan, (dl)-N-allyl-N-normetazocine, N-N-dimethyl-1-phenylcyclohexylamine, N-(n-butyl)-1-phenylcyclohexylamine, 1-[1-(2-thienyl)cyclohexyl]pyrrolidine, and N-(s-butyl)-1-phenylcyclohexylamine, in agreement with previous reports. Rats in group 3 discriminated PCP (lever 1) versus saline, cyclazocine, dextrorphan, phenobarbital, or mescaline (lever 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparison of four-drug discriminations in training compartments with four identical levers versus four different responses manipulanda.

Rats were trained to discriminate between four dissimilar drugs (phenobarbital, nicotine, fentanyl, and methylphenidate) in compartments which contained either four identical levers or four dissimilar response manipulanda. During successive training sessions, the drug condition was cycled through the four training conditions. The objective was to compare speed of acquisition and asymptotic accuracy of discriminative control in the following types of compartments: (1) Undecorated compartments with four identical levers; (2) Compartments with four dissimilar response manipulanda (lever, wheel, nosepoke, panel); (3) Four-lever compartments with a unique sensory environment surrounding each lever; (4) Compartments with four dissimilar manipulanda, each surrounded by a unique sensory environment. The required four-drug discrimination were learned in all training compartments. Independent variables that produced statistically significant effects on speed of acquisition and/or asymptotic accuracy included drug, dosage, use/nonuse of four dissimilar response manipulanda, and presence/absence of environmental decorations around each manipulandum. Although the use of four different response manipulanda and/or the use of distinctive decorations surrounding each of the four manipulanda did increase speed of acquisition, these manipulations also resulted in biases towards/against particular individual environments or manipulanda during the acquisition phase of the experiment. Such biases can complicate the interpretation of results of conventional drug discrimination studies, especially if they persist into the asymptotic accuracy phase, which was not observed in the present study.

Animals↗

Fate of explosives and their metabolites in bioslurry treatment processes.

Microcosm tests simulating bioslurry reactors with 40% soil content, containing high concentrations of TNT and/or RDX, and spiked with either [14C]-TNT or [14C]-RDX were conducted to investigate the fate of explosives and their metabolites in bioslurry treatment processes. RDX is recalcitrant to indigenous microorganisms in soil and activated sludge under aerobic conditions. However, soil indigenous microorganisms alone were able to mineralize 15% of RDX to CO2 under anaerobic condition, and supplementation of municipal anaerobic sludge as an exogenous source of microorganisms significantly enhanced the RDX mineralization to 60%. RDX mineralizing activity of microorganisms in soil and sludge was significantly inhibited by the presence of TNT. TNT mineralization was poor (< 2%) and was not markedly improved by the supplement of aerobic or anaerobic sludge. Partitioning studies of [14C]-TNT in the microcosms revealed that the removal of TNT during the bioslurry process was due mainly to the transformation of TNT and irreversible binding of TNT metabolites onto soil matrix. In the case of RDX under anaerobic conditions, a significant portion (35%) of original radioactivity was also incorporated into the biomass and bound to the soil matrix.

Biodegradation, Environmental↗