BACKGROUND AND PURPOSEDelayed gastric emptying is poorly managed. Motilin agonists are potential treatments but inadequate understanding into how enteric nerve functions are stimulated compromises drug/dose selection. Resolution is hampered by extreme species dependency so methods were developed to study human gastrointestinal neuromuscular activities and the neurobiology of motilin.
EXPERIMENTAL APPROACHProtocols to study neuromuscular activities were developed for different regions of human stomach and intestine (71 patients) using circular muscle preparations and electrical field stimulation (EFS) of intrinsic nerves. Other tissues were fixed for immunohistochemistry.
KEY RESULTSEFS evoked contractions and/or relaxations via cholinergic and nitrergic neurons, with additional tachykinergic activity in colon; these were consistent after 154 min (longer if stored overnight). Motilin 1-300 nM and the selective motilin agonist GSK962040 0.1-30 mM acted pre-junctionally to strongly facilitate cholinergic contractions of the antrum (Emax ª 1000% for motilin), with smaller increases in fundus, duodenum and ileum; high concentrations increased baseline muscle tension in fundus and small intestine. There were minimal effects in the colon. In the antrum, cholinergic facilitation by motilin faded irregularly, even with peptidase inhibitors, whereas facilitation by GSK962040 was long lasting. Motilin receptor immunoreactivity was identified in muscle and myenteric plexus predominantly in the upper gut, co-expressed with choline acetyltransferase in neurons.
CONCLUSIONS AND IMPLICATIONSMotilin and GSK962040 strongly facilitated cholinergic activity in the antrum, with lower activity in fundus and small intestine only. Facilitation by motilin was short lived, consistent with participation in migrating motor complexes. Long-lasting facilitation by GSK962040 suggests different receptor interactions and potential for clinical evaluation.
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AbbreviationsChAT, choline acetyltransferase; EFS, electrical field stimulation; Emax, maximum response to agonist; L-NAME, Nw-nitro-L-arginine methyl ester; MMC, migrating motor complex; NK, neurokinin; TTX, tetrodotoxin BJP British Journal of Pharmacology
A unique method of biodegradation of commercial polyethylene by using simultaneously a bio-surfactant produced by Bacillus licheniformis and Lysinibacillus bacterium in various combinations was investigated in this study.
High-molecular-weight polyethylene is resistant to natural environmental degradation for its crystalline, hydrophobic structure. In this study, waste polyethylene bags are chemically oxidized at 80 C for 5 days by potassium dichromate solutions of various concentrations along with sulfuric acid. Absorbance peaks of carbonyl and carboxylate ions in the Fourier transform infrared spectroscopy spectra and formation of amorphous phase from crystalline one as indicated in X ray diffraction studies of oxidized polyethylenes indicate the formation of a polar hydrophilic and low-molecular-weight material after oxidation. From the scanning electron microscopy studies, it is observed that reacted polyethylene surface is disintegrated and numerous fissures are formed throughout the surface. The respective weight loss of incubated oxidized polyethylene with Phanerochaete chrysosporium (MTCC-787) after 15 days of incubation is 70%, respectively, in black liquor-glucose-malt extract medium. As both lignin peroxidase (LiP) and manganese peroxidase (MnP) were detected in this media, further degradation of oxidized polyethylene is carried out in four different media with varying amount of N and Mn. The weight loss is observed only in media with excess nitrogen (N) and limited manganese (Mn), the condition which enhances the presence of LiP and MnP. This indicates that these enzymes are essential for degradation of lignin as well as oxidized polyethylene. UV spectroscopic studies indicate 40% decrease in the lignin concentration. This process of fungal degradation of chemically oxidized polyethylene using black liquor is very quick compared to the other related studies, leading to the simultaneous degradation of two waste materials, polyethylene and black liquor.
Polyethylene was incubated with a bio-surfactant producing bacterium B. licheniformis for 2 months in a suitable media. Low concentrations of NaCl were added to study its effect on the bio-surfactants activity. Being amphiphilic, the surfactant has a unique ability to decrease the surface energy, and this decrease measured using the surface tension of the medium was 50%. The surfactant was able to oxidize both control (unoxidized) and pre-oxidized polyethylene during incubation. The oxidation level of the control polyethylene sample was increased in the presence of NaCl, and the oxidation level was higher in the presence of 1% NaCl as compared to that found with 0.5% NaCl. A higher amount of surfactant was also produced, as observed by the comparatively low surface tension in the presence of NaCl. During the bio-oxidation of polyethylene, higher amounts of unsaturated hydrocarbons were formed as compared to carbonyl groups. This oxidation was also observed through the reduced crystalline property and cracked polyethylene surface using SEM. It was also observed that the product formed during the oxidation by the bio-surfactant could be solubilised into liquid media. For this rapid loss of oxidation product, a decrease in the mechanical properties of all the treated polyethylene samples was observed, and this deterioration was highest in the case of the pre-oxidised polyethylene incubated with the bio-surfactant for 2 months. In this study, a novel unique method for the biooxidation of polyethylene using a bio-surfactant was established.
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