SPECIFIC STIMULATION OF MIGRATION OF HUMAN KERATINOCYTES BY μ -OPIATE RECEPTOR AGONISTS
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There are several indications that neuropeptides, especially the opiate receptor agonists, modulate the immune response by stimulating the formation of granulation tissue and enhancing the reepithelialization. We observed that the mu-opiate receptor ligand beta-endorphin stimulates the migration of cultured human foreskin keratinocytes. After 1 hour exposure to 1 microM beta-endorphin, the keratinocytes experienced an increase of cell diameter by cellular elongation and stimulation of migration. Dynorphin had a lesser effect under the same condition. The opiate receptor antagonist naltrexone significantly reduced the effect of beta-endorphin on keratinocyte migration. This migratory effect of mu-opiate receptor agonists in vitro indicates that the opioid peptides, released in wounds, could play a key role in the final reepithelialization and tissue regeneration in wound healing. This new knowledge will help us not only to understand the mechanism of wound healing but also to improve the therapeutic strategy in the healing of painful chronic wounds.Keywords:
Dynorphin
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Granulation tissue
AbstractThe narcotic antagonist, naltrexone, was studied in 242 patients during a 6-year period. Although a large number of subjects discontinued naltrexone abruptly, treatment was related to a significant decrease in opiate and nonopiate drug use. Methods for improving retention during induction and maintenance are discussed and posttreatment outcome results are presented. The authors conclude that naltrexone may be a useful short-term treatment option for opiate dependence.
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Combining naltrexone and clonidine under general anesthesia is being used to shorten opiate detoxification. This study determined the one-year relapse rate of persons detoxified using this ultrarapid method in conjunction with naltrexone maintenance and counseling. Structured telephone interviews were held with 83 out of a random sample of 113 male patients who were detoxified via the ultrarapid method more than one year before the interview (average 1.5 years) and their significant others. Relapse was defined as at least two weeks of daily opiate use. According to patients and significant others, 57 percent of patients had not relapsed. This rate is better than rates obtained in studies of other detoxification methods.
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A group of 93 patients consecutively treated for Opiate Dependence (DSM) III) was examined and the relationship between detoxification outcome and treatment with an opiate antagonist (naltrexone), sociodemographic characteristics and clinical features was studied. The treatment with naltrexone followed detoxification in 46 cases (50%). Average retention is 16.7 weeks, much longer than reported in the literature. This outcome is ascribed to: 1) better social adjustment of the population considered, in terms of employment, relatives' involvement in the treatment and Opiate Dependence in partners; 2) introduction of naltrexone in a multimodal program, including psychological and social support.
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Naltrexone has been used for many years as an opiate antagonist for maintenance treatment to prevent relapse in opiate addiction and, more recently, for rapid opiate detoxification with and without general anaesthesia. Naltrexone is useful for rapid detoxification without anaesthesia. However, the detoxification procedure under anaesthesia lacks a scientific basis. There is no clear evidence of the efficacy of naltrexone maintenance treatment. Poor compliance and possible receptor sensitisation means there may be a potentially increased risk of mortality through opiate overdose following cessation of naltrexone treatment and relapse into addiction.
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The oral opiate antagonist naltrexone is in regular use in clinical practice with abstinent opiate-dependent individuals. Acute opioid withdrawal is a well-recognised consequence of consuming naltrexone while opiate dependent. Two cases of naltrexone-induced opiate withdrawal are reported. The compressed nature of the withdrawal syndrome in both of these cases and the implications for the management of protracted withdrawal symptoms are discussed. The theoretical implications of this experimental and clinical phenomenon are reviewed.
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