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Biomedical subjects

E J Coleman

Publications and source records attributed to E J Coleman.

18 recordsLinked to original sources

Local anesthetics attenuate lysophosphatidic acid-induced priming in human neutrophils.

UNLABELLED: Lysophosphatidic acid (LPA) is an intercellular phospholipid mediator with a variety of actions that suggest a role in stimulating inflammatory responses. We therefore studied its actions on neutrophil (PMN) motility and respiratory burst. Because local anesthetics (LA) inhibit LPA signaling and attenuate PMN responses, we also investigated the effects of LA on these actions. Chemotaxis of human PMNs under agarose toward LPA (10(-10)-10(-3) M) was studied, with and without 1 h prior incubation in lidocaine (10(-9)-10(-4) M). Priming as well as activating effects of LPA on PMNs were measured using a cytochrome-c assay of superoxide anion (O2-) production. PMNs were incubated with lidocaine, tetracaine, or S-(-) ropivacaine (all at 10(-6)-10(-4) M) for 10 min or 1 h to assess interference with LPA signaling. LPA demonstrated chemoattractive effects towards human PMNs; this effect was concentration-dependently attenuated by lidocaine. LPA alone did not activate PMNs. However, it acted as a priming agent. LA in clinically relevant concentrations decreased (O2-) production induced by LPA/N-formylmethionine-leucyl-phenylanaline. LPA acts as a chemoattractant and priming agent; however, it does not activate PMNs. LA, in clinically relevant concentrations, attenuate chemotactic and metabolic responses as a result of LPA. These results may explain the antiinflammatory effect of local anesthestics. IMPLICATIONS: Lysophosphatidic acid (LPA) influences two functions of human neutrophils, migration and metabolic activity. It acted as a chemoattractant and a priming-but not activating-agent. Responses to LPA were attenuated by local anesthetics in clinically relevant concentrations.

Anesthetics, Local↗

Developmental regulation of FKBP65. An ER-localized extracellular matrix binding-protein.

FKBP65 (65-kDa FK506-binding protein) is a member of the highly conserved family of intracellular receptors called immunophilins. All have the property of peptidyl-prolyl cis-trans isomerization, and most have been implicated in folding and trafficking events. In an earlier study, we identified that FKBP65 associates with the extracellular matrix protein tropoelastin during its transport through the cell. In the present study, we have carried out a detailed investigation of the subcellular localization of FKBP65 and its relationship to tropoelastin. Using subcellular fractionation, Triton X-114 phase separation, protease protection assays, and immunofluorescence microscopy (IF), we have identified that FKBP65 is contained within the lumen of the endoplasmic reticulum (ER). Subsequent IF studies colocalized FKBP65 with tropoelastin and showed that the two proteins dissociate before reaching the Golgi apparatus. Immunohistochemical localization of FKBP65 in developing lung showed strong staining of vascular and airway smooth muscle cells. Similar areas stained positive for the presence of elastic fibers in the extracellular matrix. The expression of FKBP65 was investigated during development as tropoelastin is not expressed in adult tissues. Tissue-specific expression of FKBP65 was observed in 12-d old mouse tissues; however, the pattern of expression of FKBP65 was not restricted to those tissues expressing tropoelastin. This suggests that additional ligands for FKBP65 likely exist within the ER. Remarkably, in the adult tissues examined, FKBP65 expression was absent or barely detectable. Taken together, these results support an ER-localized FKBP65-tropoelastin interaction that occurs specifically during growth and development of tissues.

Amino Acid Sequence↗

Activities of antimicrobial agents against intracellular pneumococci.

Pneumococci can enter and survive inside human lung alveolar carcinoma cells. We examined the activity of azithromycin, gentamicin, levofloxacin, moxifloxacin, penicillin G, rifampin, telithromycin, and trovafloxacin against pneumococci inside and outside cells. We found that moxifloxacin, trovafloxacin, and telithromycin were the most active, but only telithromycin killed all intracellular organisms.

Anti-Bacterial Agents↗

The effect of triclosan on mediators of gingival inflammation.

Triclosan (2,4,4',-trichloro-2'-hydroxydiphenylether) is a well-known and widely used nonionic antibacterial agent which has recently been introduced in toothpastes and mouthrinses. The efficacy of triclosan-containing toothpaste and mouthrinse to reduce both plaque and gingivitis in long-term clinical trials has been well documented. Until recently, it was generally assumed that triclosan's effect on gingival inflammation was due to its antimicrobial and anti-plaque effect. It has now become apparent that triclosan may have a direct anti-inflammatory effect on the gingival tissues. Several in vitro studies were conducted to evaluate the effect of triclosan on 4 primary enzymes of the pathways of arachidonic acid metabolism, cyclo-oxygenase 1, cyclo-oxygenase 2, 5-lipoxygenase and 15-lipoxygenase. These pathways lead to the production of known mediators of inflammation such as the prostaglandins, leukotrienes and lipoxins. Triclosan inhibited both cyclooxygenase 1 and cyclo-oxygenase 2 with IC-50 values of 43 microM and 227 microM, respectively. Triclosan also inhibited 5-lipoxygenase with an IC-50 of 43 microM. The 15-lipoxygenase was similarly inhibited by triclosan with an IC-50 of 61 microM. Hence, triclosan has the ability to inhibit both the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism with similar efficacy. In cell culture experiments, it was found that triclosan inhibited IL-1 beta induced prostaglandin E2 production by human gingival fibroblasts in a concentration dependent manner, and at relatively low concentrations. These data, taken together, indicate that triclosan can inhibit formation of several important mediators of gingival inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Infective Agents, Local↗

Influence of an anticalculus mouthrinse treatment on the dentition and periodontium in beagle dogs.

This research evaluated the effect of an anticalculus mouthrinse, containing 3.3% pyrophosphate anion and 1.0% of a copolymer of vinylmethyl ether and maleic acid (Gantrez), on calculus formation, gingivitis, gingival recession, and epithelial attachment in beagle dogs over a one-year period of time, compared to a distilled water rinse. Each was applied twice a day for the one-year period. Compared to the control, the anticalculus mouthrinse resulted in significant reductions in the formation of calculus and gingivitis, as well as a prevention of loss of epithelial attachment in the beagle dogs. The results from this investigation suggest that it is possible to mitigate both probing epithelial attachment loss and increases in probing pocket depth at the calculus prone sites through the use of an anticalculus mouthrinse.

Analysis of Variance↗

Small bowel injuries following blunt abdominal trauma. Early recognition and management.

We reviewed the cases of 15 patients with intestinal perforation following blunt abdominal trauma, which occurred between 1971 and 1988. Twelve patients were treated at The Mary Imogene Bassett Hospital (Cooperstown, NY); three other patients were treated at surrounding area hospitals. These injuries included 11 motor vehicle accidents, three low-velocity impact injuries, and one blast injury. There were four duodenal, ten jejunal, and two ileal injuries. Five patients who were operated on within 12 hours had classic signs of peritonitis or gross blood on diagnostic peritoneal lavage. Four patients were operated on after 12 hours, and six after 24 hours; physical signs were subtle in this group. Pain was a universal finding but was usually moderate; nausea and vomiting were frequent early findings in the ten patients with late recognition. An altered sensorium due to intoxication or head injury was present in three of ten patients operated on after 12 hours. Laboratory determinations, including a white blood cell count and amylase analysis, as well as abdominal radiographs, were often not helpful. Diagnostic peritoneal lavage is an important test, but when it is performed within four hours post-injury, it may yield false negative findings in up to 50% of patients and may need to be repeated. Computer tomographic scanning should employ oral and intravenous contrast to increase accuracy; perforation of a hollow viscus may not be immediately recognized. Four of the five patients operated on within 12 hours had an uncomplicated course. Complications occurred in all six patients operated on beyond 24 hours and included intraabdominal abscesses in five, and death for one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Nonbactericidal approach to reduce colonization of plaque microflora on teeth in vitro and in vivo.

A non-antibacterial, surface-modifying, perfluorosulfonamidoalkyl ester of phosphorous acid (PSAEP, 1) was adsorbed to saliva-coated hydroxyapatite disks in vitro. Pretreatment of saliva-coated hydroxyapatite beads with different concentrations of 1 markedly reduced the adherence of radiolabeled Streptococcus mutans or Actinomyces viscosus when compared with the buffer-treated controls. Pretreatment of the cells with the compound also significantly impaired their subsequent attachment to saliva-coated hydroxyapatite. In a low surface-to-volume ratio adsorption model, i.e., saliva-coated hydroxapatite disks, pretreatment with 1 for 1 min markedly reduced the adsorption of A. viscosus to the disks. A 1% solution applied topically twice a day significantly (alpha = 0.05) reduced S. mutans-induced smooth and fissure caries in rats. The effect of 0.05% 1 in a rinse was also evaluated on experimental gingivitis in beagle dogs for 6 weeks. A topical application twice a day significantly (alpha = 0.05) reduced plaque-induced gingivitis when compared to that achieved with the placebo. Microbial analyses of the plaque adjacent to gingiva indicated reduction in filamentous medium and large spirochetes as compared with that seen in the pretreatment phase. Collectively, the results show that it is possible to reduce dental caries and gingivitis via an interference with the specific adsorption of organisms to teeth.

Actinomyces↗

Penetration of dental plaque components into gingiva: sequential topical treatments with hyaluronidase and streptococcal polysaccharide in rats.

EIGHTY-FIVE Sprague-Dawley rats were used in two experiments to determine the conditions necessary to permit transepithelial penetration by deleterious macromolecules in murine oral mucosa. In experiment one, Group I was a water and diet control; Group II mucosa was treated with hyaluronidase; Group III with streptococcal polysaccharide; and Group IV with hyaluronidase, followed by treatment with the polysaccharide. In the second experiment, the histological effects of the streptococcal polysaccharide were quantified by administering a series of concentrations, from 10 mg/ml to 100 microgram/ml. The results suggest that tissue-damaging plaque components, such as hyaluronidase and polysaccharide, act in combination to pass through the epithelial structures into the subjacent connective tissues to cause destructive changes in rat gingiva. Such changes may possibly be related to those seen in the periodontium when it is adjacent to dental plaque.

Animals↗