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Study of biodegradable and self-expandable PLLA helical biliary stent in vivo and in vitro.

Biodegradable stents have advantages for the treatment of benign and malignant biliary stricture, especially eliminating the need for stent removal. In our present work, helical poly-l-lactic acids (PLLA) stent was fabricated and evaluated in vivo and in vitro. For in vivo study, bile duct injury canine models were made by transection of common bile ducts. Duct to duct anastomosis was done with helical PLLA biodegradable stents. Scanning electron microscopy (SEM) and histopathology were performed after three months. For In vitro study, sludge attachment assessment was performed. Polyethylene (PE) and PLLA membranes were immersed in human bile for two months. The samples were taken out and characterized by SEM. Self-expanding property of the helical stent was tested in 37 degrees Celsius water. The results demonstrate that the biodegradable stent had not only good biocompatibility, but also self-clearing effect to clear the attached sludge away. The self-expanding property facilitated stent implantation and also suggested possibility to be implanted endoscopically.

Absorbable Implants↗

Gd-DTPA L-cystine bisamide copolymers as novel biodegradable macromolecular contrast agents for MR blood pool imaging.

PURPOSE: The purpose of this study was to synthesize biodegradable Gd-DTPA L-cystine bisamide copolymers (GCAC) as safe and effective, macromolecular contrast agents for magnetic resonance imaging (MRI) and to evaluate their biodegradability and efficacy in MR blood pool imaging in an animal model. METHODS: Three new biodegradable GCAC with different substituents at the cystine bisamide [R = H (GCAC), CH2CH2CH3 (Gd-DTPA L-cystine bispropyl amide copolymers, GCPC), and CH(CH3)2 (Gd-DTPA cystine bisisopropyl copolymers, GCIC)] were prepared by the condensation copolymerization of diethylenetriamine pentaacetic acid (DTPA) dianhydride with cystine bisamide or bisalkyl amides, followed by complexation with gadolinium triacetate. The degradability of the agents was studied in vitro by incubation in 15 microM cysteine and in vivo with Sprague-Dawley rats. The kinetics of in vivo contrast enhancement was investigated in Sprague-Dawley rats on a Siemens Trio 3 T scanner. RESULTS: The apparent molecular weight of the polydisulfide Gd(III) chelates ranged from 22 to 25 kDa. The longitudinal (T1) relaxivities of GCAC, GCPC, and GCIC were 4.37, 5.28, and 5.56 mM(-1) s(-1) at 3 T, respectively. The polymeric ligands and polymeric Gd(III) chelates readily degraded into smaller molecules in incubation with 15 microM cysteine via disulfide-thiol exchange reactions. The in vitro degradation rates of both the polymeric ligands and macromolecular Gd(III) chelates decreased as the steric effect around the disulfide bonds increased. The agents readily degraded in vivo, and the catabolic degradation products were detected in rat urine samples collected after intravenous injection. The agents showed strong contrast enhancement in the blood pool, major organs, and tissues at a dose of 0.1 mmol Gd/kg. The difference of their in vitro degradability did not significantly alter the kinetics of in vivo contrast enhancement of the agents. CONCLUSION: These novel GCAC are promising contrast agents for cardiovascular and tumor MRI, which are later cleaved into low molecular weight Gd(III) chelates and rapidly cleared from the body.

Animals↗

Biodegradation of alkyltrimethylammonium salts in activated sludge.

Trimethylamine, dimethylamine and methylamine (actually existing as a salt form in the culture medium) were identified as the intermediates of alkyltrimethylammonium salts in activated sludge obtained from a municipal sewage treatment plant. It was considered that the quaternary ammonium salts with long alkyl chains were degraded to tertiary amine by N-dealkylation at the first stage of the biodegradation pathway. The tertiary amine formed in this pathway rapidly disappeared. In the activated sludge, biodegradabilities based on biochemical oxygen consumption and dissolved organic matter were 7.2-53.7% and 97.4-100%, respectively. These results and the disappearance of intermediates as described above indicate that long chain alkyltrimethylammonium salts are ultimately biodegradable.

Biodegradation, Environmental↗

Comparative evaluation of anaerobic biodegradability of hydrocarbons and fatty derivatives currently used as drilling fluids.

The examination of a number of potential and currently used carrier fluids for invert emulsion drilling fluids in the ECETOC screening test revealed clear differences with respect to their easy anaerobic biodegradability. Fatty acid- and alcohol-based ester oils exhibited excellent anaerobic degradation to the gaseous final end products of the methanogenic degradation pathway, methane and carbon dioxide. Mineral oils, dialkyl ethers, alpha-olefins, polyalphaolefins, linear alkylbenzenes and an acetal-derivative were not or only slowly degraded. Although the poor degradation results obtained in the stringent ECETOC screening test may not be regarded as final proof of anaerobic recalcitrance, nevertheless, these results were found to be in line with the present understanding of the structural requirements for anaerobic biodegradability of chemicals. The validity of the conclusions drawn is corroborated by published results on the anaerobic biodegradation behaviour of ester oils, mineral oils and alkylbenzenes in marine sediments.

Alcohols↗

Anaerobic biodegradation potentials in digested sludge, a freshwater swamp and a marine sediment.

An anaerobic gas production test was used for determining the potential biodegradation of 22 organic chemicals under methanogenic conditions. Nine of the examined chemicals were extensively mineralized (> 75%) both in sewage sludge and in a freshwater swamp indicating good agreement between biodegradation potentials in these habitats. Samples from a marine sediment showed a less extensive mineralization of most of the test chemicals, and lag periods of several weeks often preceded net gas production. As marine sediments usually contain sulfate at the time of collection, the assessment of biodegradation potentials in such environments is probably more reliable when using a method based on sulfate reduction instead of methanogenic gas production. The results of the tests indicate that the commonly recommended washing of sludge solids can be eliminated by applying a more diluted inoculum.

Anaerobiosis↗

Determination of the aerobic biodegradability of polymeric material in a laboratory controlled composting test.

A laboratory method is presented for investigating the biodegradation of an organic test material in an aerobic composting system based on the evolution of carbon dioxide. In addition to carbon conversion, biodegradation can also be monitored through weight loss and physical disintegration. The test method is different from other biodegradation tests, especially aquatic tests, because of the elevated temperature representative for real composting conditions and also because of enhanced fungal degradation activities. A ring test was run using paper and poly-beta-hydroxybutyrate/valerate as test materials and cellulose powder as a reference material. The test results and the experience gained by the participants showed that the method is suitable and practicable. Experience with real technical-scale composting facilities confirms that the method provides test results of high predictive value. The test is designed to become a European Standard in connection with determining the compostability of packagings and packaging materials.

Bacteria, Aerobic↗

Factors affecting the biodegradation of toluene in soil.

The biodegradation of toluene in soil microcosms was examined in order to identify the physical, chemical, and biological factors which determine the fate and lifetime of organic chemicals in soils. Toluene degradation rates were proportional to the initial substrate concentration and these rates reached a maximum at a concentration of 200 micrograms/g. No degradation occurred above this concentration presumably due to the toxicity of the hydrocarbon to the soil microorganisms. Small differences were observed in the degradation rates in soils at different moisture content. However, the availability of water in soil appeared to limit toluene degradation only at a very low water content. The lifetime of toluene in soil was also related to the initial level and activity of the soil microorganisms. Toluene was metabolized rapidly in those soils which initially contained high levels of degrading microorganisms. Furthermore, exposure of the soil to toluene resulted in an increase in the number of degrading organisms. The lack of inorganic nutrients such as nitrogen prevented complete degradation of toluene in a clay soil which contained high levels of degrading microorganisms. The biodegradation of organic chemicals in soil is not an intrinsic property of the molecule and cannot be predicted without first delineating the environment in which it is found. The biodegradation of a compound is defined by the biological, physical, and chemical characteristics of the soil environment. The lifetime of a chemical in soil results from a combination of all three of these parameters.

Bacteria↗

Biodegradability simulation studies in semicontinuous activated sludge reactors with low (microgram/L range) and standard (ppm range) chemical concentrations.

The official OECD/EEC activated-sludge biodegradability simulation test has been criticised for providing a poor simulation of the biodegradability behaviour of industrial chemicals in municipal sewage treatment plants due to the high dosed concentration of test substance of approx. 20-40 mg/L necessitated by measuring compound removal by DOC-analysis. Realistic concentrations of industrial chemicals are more commonly in the microgram/L range. With increasing concentration both the kinetic regime of degradation and the adaptation behaviour can be expected to change. Results from a comparative study in semicontinuous reactors with high (20 mg DOC/L) and low (10 micrograms test substance/L) inlet concentrations of aniline, 4-chloroaniline, and pentachlorophenol, conducted by means of 14C-tracer technique, revealed large differences in biodegradation behaviour between the two concentration levels and led to the following tentative general conclusions: 1) the percentage of test compound removed by unadapted sludge tends to be higher with test compound dosed at trace concentrations than at standard (high) concentrations (20 mg/DOC/L); 2) by contrast, in successfully adapted systems, the removal percentage (and the "extent of adaptation") may be largest with high concentrations; 3) the use of real sewage instead of peptone synthetic sewage better safeguards against sludge deterioration, in particular at low sludge retention times, and tends to increase the adaptation potential of the sludge; 4) the use of synthetic sewage in combination with regular reinoculation of the reactor (in this study by replacing 10% of the sludge with freshly collected sludge once a week) may be a feasible alternative to using real sewage.

Aniline Compounds↗

A respirometer with improved sensitivity for ready biodegradation testing.

In this paper we describe a respirometry system with improved sensitivity, that was used to test materials at concentrations down to 3 mg C/l. Data obtained with this system, operating under the conditions of the OECD ready biodegradability tests 301B, C, D and F, is presented and compared with CO2-production data obtained under 301B conditions in the Sealed Vessel Test. For simple materials, the shape of the curves, not easily seen with CO2 production or DOC removal data, is clearly biphasic with a sigmoidal first part-suggesting growth of the inoculum on the test materials. For a selection of rapidly and readily biodegradable materials, the removal of soluble carbon was complete at the end of the first, sigmoidal part of the biodegradation curve; It is speculated that the remainder of the curve probably represents the mineralisation of part of the biomass. The respirometer generated many hundred data points per degradation curve and Monod or exponential growth models were fitted and growth parameters were derived. Growth rates under ready test conditions were derived for six materials as follows: aniline mu = 0.31 h-1, ethanolamine mu = 0.13 h-1, 1,6-hexanediol mu = 0.05 h-1, pentaerythritol mu = 0.04 h-1, C12.8EO mu = 0.13 h-1 and commercial LAS mu = 0.05 h-1.

Biodegradation, Environmental↗

Ultimate biodegradation of 2-, 3- and 4-nitrotoluene.

The biodegradation of 2-, 3- and 4-nitrotoluene was investigated in a simple laboratory test. All three isomers are shown to be biodegradable in a die-away test after adaptation of the inoculum, though different results were obtained with different types of activated sludges used as inoculum in the static test. The adaptation procedure, employed in this study, was a modification of a test method described by Pitter in 1976. It appeared that adaptation in a semi-continuous activated sludge system was most successful when a composite sludge was used consisting of activated sludge from a communal sewage plant and an extract of river mud. meta-Nitrotoluene was more resistant to attack by a mixed population of aquatic micro-organisms than the other isomers. The procedure used in this study is proposed as an attractive alternative for those methods which are recommended by the OECD and the EEC, to test the so-called 'inherent biodegradability'.

Bacteria↗

Predictive QSAR models for estimating biodegradation of aromatic compounds.

The development of valid structure biodegradation relationships (SBRs) is restricted by the lack of reproducible published data and by the considered endpoint of degradation data. A classification scheme is required for comparative evaluation of degradation data obtained by different test methods. SBRs based on substructure indicators are available for application to most compounds, but the reliability is still uncertain. SBRs based on physico-chemical parameters are only available for a few classes of compounds based on specific test methods. A combination of several SBRs covering the various transformation pathways provides a promising tool for predicting biodegradability. Two models describing biodegradation are introduced.

Biodegradation, Environmental↗

On the biodegradation of poly-beta-hydroxybutyrate (PHB) homopolymer and poly-beta-hydroxybutyrate-hydroxyvalerate copolymers.

The known biodegradability of PHB in certain biological environments has led to its proposed use as a 'biodegradable' implant material. Monofilaments of PHB homopolymer and two PHV-PHB copolymers have been studied in vivo and in vitro and assessed for changes in mechanical properties and topography. In vivo biodegradation was only observed with PHB when pre-degraded by 10.0 Mrad of gamma-irradiation before implantation. High temperature in vitro hydrolysis suggested that PHV copolymer additions retarded the rate of degradation of PHB. Hydration reactions had most effect on the ultimate tensile properties of the materials. In contrast, the elastic properties appeared to be relatively unaffected.

Animals↗

Biodegradation and brain tissue reaction to poly(D,L-lactide-co-glycolide) microspheres.

The therapeutic application of neuroactive molecules in neuroscience is limited, due to the problems posed by the administration of these drugs (peripheral metabolism, systemic effect and passage of the blood-brain barrier). One solution is the implantation in the brain of biodegradable polymer devices with controlled release of a neuroactive drug. The biodegradation and tissue reaction of the copolymer poly(D,L-lactide-co-glycolide) microspheres prepared by the solvent evaporation method, radiosterilized and stereotactically implanted in the rat brain were studied by routine staining, immunohistochemistry and transmission electronic microscopy. The brain tissue reaction observed was a non-specific astrocytic proliferation and a macrophagous-microglial cell reaction, typically found following damage to the central nervous system. Some foreign-body giant cells were observed and the inflammatory and macrophagous reaction decreased dramatically after 1 month and almost ended after 2 months when the microspheres were totally biodegraded. The copolymer poly(D,L-lactide-co-glycolide) microspheres may be considered biocompatible to the brain tissue.

Animals↗

Comparison of methods for the biodegradability evaluation of soluble and insoluble organochemicals.

Pyridine and nitrilotriacetic acid sodium salt as models of soluble compounds and linear dodecylbenzene, branched dodecylbenzene, and stearic acid as models of insoluble compounds were compared for their biodegradability in three tests: the ODCE modified test and the Sturm and enrichment culture tests. The degradation of soluble compounds was measured as dissolved organic carbon removal and CO2 evolution, while for the insoluble compounds, which were tested only in the Sturm test, CO2 evolution was determined. The individual tests were characterized by comparing their results with those obtained in the others. Comparable biodegradation values higher than 90% were obtained for the soluble compounds. The Sturm test proved to be very suitable for the evaluation of biodegradability of either soluble or insoluble compounds.

Acetates↗

Aerobic and anaerobic biodegradation of nitrilotriacetate in subsurface soils.

Studies were conducted to characterize mineralization of nitrilotriacetate (NTA) in subsurface soils under aerobic and anaerobic conditions. Chemical (redox indicator, resazurin) and biological (dentrification) markers were used as indicators of anaerobic conditions in the test system. The indigenous microflora in subsurface soils previously exposed to septage containing NTA were able to rapidly mineralize NTA under aerobic and anaerobic conditions. The half-lives (t1/2) of mineralization for NTA in aerobic soils ranged from 87 to 160 hr. Biodegradation of NTA under anaerobic conditions where NO3- indicates that a mechanism exists for the anaerobic biodegradation of this substrate. NTA biodegradation can occur readily in the absence of molecular oxygen and the NTA-monooxygenase which are required for the aerobic mineralization of this substrate. These results provide the first evidence that the indigenous microflora in subsurface soils of septic tank tile fields can rapidly degrade NTA under anaerobic conditions.

Acetates↗

A shake-flask test for estimation of biodegradability of toxic organic substances in the aquatic environment.

Disadvantages of current biodegradation tests are examined: the need for high substrate concentrations, lack of parent compound concentration measurements, no estimation of sediment effects, failure to indicate compounds to which microbial populations must adapt to degrade, and lack of site specificity in innocula selection. A modified river die-away test is proposed for determining biodegradability of organic compounds and testing for toxic degradation products. The present test uses shake flasks containing sterile (2% formalin) and nonsterile site water: both with, and without, site sediment (500 mg/liter). Concurrent toxicity testing with mysids or daphnids provides a sensitive assay for the detection of toxic metabolites. Examples of three test compounds are given: methyl parathion, which undergoes rapid, sediment-mediated biodegradation; dibutylphthalate, to which some microbial communities exhibit an adaptation phenomenon; and methoxychlor, which has a relatively low water solubility and high sediment partition coefficient. The relative merits of this test procedure are discussed.

Animals↗

Biodegradation kinetics of linear alkylbenzene sulfonate in sludge-amended agricultural soils.

The kinetics of ultimate biodegradation (mineralization to CO2) of linear alkylbenzene sulfonate (LAS) were studied in sludge-amended agricultural soils for a series of pure chain length LAS homologs containing 10 to 14 carbon atoms in the alkyl chain. Degradation rates were measured by following the production of 14CO2 from uniformly 14C-ring-labeled material. In general, degradation of LAS was rapid in soil over a broad concentration range (0.1 to 10 times the expected environmental concentration) and demonstrated little variation among different homologs. Half-lives for mineralization of the benzene ring ranged from 18 to 26 days and were not significantly different for any homolog over the range of alkyl chain lengths tested. Half-lives measured for LAS degradation in these studies were comparable to values reported in the literature and also to values obtained for naturally occurring materials (stearic acid, cellulose) typically present in soil environments. On the basis of the results of the present studies and those of other investigators, it is concluded that soil environments exposed to LAS in sewage sludges contain microbial communities which can actively metabolize this material. Rates of biodegradation of the benzene ring, the final step in the LAS biodegradation pathway prior to complete mineralization, are also sufficient to prevent LAS from accumulating in soil environments.

Alkanesulfonates↗

Simple method to prolong the closed bottle test for the determination of the inherent biodegradability.

A method to prolong the closed bottle test up to 200 days is described and validated. This prolonged closed bottle test has been used to determine the biodegradability of "recalcitrant" and toxic organic compounds. The results obtained in the prolonged closed bottle test are in accordance with those mentioned in the literature on biodegradation of organic compounds in waste water purification plants and on the isolation of microorganisms capable of utilizing these compounds as carbon and energy source. Furthermore, this test may prevent discrepancies and unexplainable results obtained in a 28-day test. The test has the potential to be used as an inherent biodegradability test when recognized by the authorities.

Biodegradation, Environmental↗