PLATELET MAO AS A MARKER FOR SMOKING CESSATION

在文献中有一个共识，我们的初步数据证实，在血小板和大脑中，吸烟者的MAO活性明显低于不吸烟者或戒烟者。研究还表明，除尼古丁外，烟草烟雾中还有一种成分能抑制MAO活性。然而，抑制的性质（可逆或不可逆），戒烟后MAO活性恢复的时间过程，以及吸烟的量和持续时间与MAO活性的关系尚不清楚。在拟议的研究中，吸烟者将从戒烟计划中招募。血液样本将在受试者仍在吸烟的“戒烟日”以及戒烟后的第7、14和28天采集。将检测这些样本和非吸烟对照组样本的血小板MAO活性。这样，每个吸烟受试者除了与非吸烟对照组进行比较外，还可以作为自己的对照。吸烟受试者也将被要求报告复发情况，并在两天内再次抽血。我们还将评估选择性MAO-B抑制剂Ro 19-6327在所有受试者血小板中的结合情况。初步结果表明，Ro 19-6327结合在吸烟者和非吸烟者中的MAO活性相似。对数据的分析将包括评估MAO活性正常化的时间进程，MAO活性与CO和可tinine水平以及与人口统计学和吸烟史信息的关系，以及MAO活性变化与Ro 19-6327结合变化的相关性。建议的商业应用：开发一种具有相对较长半衰期的敏感和特异性的戒烟和复发标志物，对临床医生和其他正在实施的戒烟计划具有重要价值。如果血小板Ro 19-6327结合的测量被证明是可靠和有效的，则可以开发和销售一种非放射性检测方法，为临床环境中的从业者提供准确和信息丰富的结果，并可以提高戒烟的动机。

There is a consensus in the literature, and our preliminary data confirm, that MAO activity, both in platelets and brain, is significantly lower in smokers than in non-smokers or ex-smokers. It has also been shown that there is a component in tobacco smoke, other than nicotine, which inhibits MAO activity. However, the nature of the inhibition (reversible or irreversible), and the time course for recovery of MAO activity after smoking cessation, as well as the relationship of amount and duration of smoking to MAO activity, are not known. In the proposed study, smokers will be recruited from a smoking cessation program. Blood samples will be obtained on the "quit date", while subjects are still smoking, and at 7, 14 and 28 days following smoking cessation. Platelet MAO activity in these samples and in samples from non-smoking control subjects will be assayed. In this way, each smoking subject will serve as his/her own control, in addition to being compared to non-smoking control subjects. Smoking subjects will also be asked to report relapse and to return within two days to have another blood sample drawn. We will also assess binding of the selective MAO-B inhibitor, Ro 19-6327, in platelets of all subjects. Preliminary results show that Ro 19-6327 binding parallels MAO activity in smokers and non-smokers. Analysis of the data will include assessment of the time course of normalization of MAO activity, the relationship of MAO activity to CO and cotinine levels and to demographic and smoking history information, and the correlation of changes in MAO activity with changes in Ro 19-6327 binding. PROPOSED COMMERCIAL APPLICATION: The development of a sensitive and specific marker of smoking cessation and relapse, that has a relatively long half-life, would be of significant value to clinicians and other operating smoking cessation programs. If the measurement of platelet Ro 19-6327 binding proves reliable and valid, a non-radioactive assay can be developed and marketed that would provide accurate and informative results to the practitioner within a clinical setting, and that could improve motivation for smoking cessation.