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FASEB J. 2003 Aug 1 [Epub ahead of print].
The alpha7 nicotinic acetylcholine receptor in schizophrenia: decreased mRNA levels in peripheral blood lymphocytes.

Perl O, Ilani T, Strous RD, Lapidus R, Fuchs S.

Recent studies have suggested that the alpha7 nicotinic acetylcholine receptor (alpha7 AChR) may play a role in the pathogenesis of schizophrenia. In search for peripheral biological markers for schizophrenia we have investigated alpha7 mRNA levels in peripheral blood lymphocytes (PBLs) of schizophrenic patients and healthy controls. Peripheral blood samples were collected from medicated and non-medicated (drug naive) schizophrenic patients as well as from healthy (non-mentally ill) smokers and non-smokers. RNA was prepared from isolated lymphocytes. Polymerase chain reaction products specific for human alpha7 AChR were quantified by densitometry using Scion image-analysis (shared NIH software). We observed a significant decrease of alpha7 mRNA levels on PBLs of schizophrenic patients compared with controls. The decrease in alpha7 mRNA levels was not a result of medication management, because non-medicated schizophrenic patients displayed the same level of reduction in alpha7 mRNA as did patients receiving medication. In addition, we exclude the possibility that the observed decrease in alpha7 mRNA levels resulted from nicotine consumption in smoking, because healthy smokers exhibited the same levels of alpha7 mRNA as non-smokers. We propose that alpha7 AChR may be involved in the pathophysiology of the disease and may serve as a reliable peripheral biological marker in schizophrenia.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12897067&dopt=Abstract [PubMed - as supplied by publisher]

Eur J Clin Pharmacol. 2003 Jul 25 [Epub ahead of print].
A naturalistic cohort study on effectiveness, safety and usage pattern of an over-the-counter nicotine patchCohort study on smoking cessation.

Hasford J, Fagerstrom KO, Haustein KO.

Department of Medical Informatics, Biometry and Epidemiology, University of Munich, Marchioninistr 15, D-81377, Munchen, Germany.

INTRODUCTION. Nicotine replacement therapies (NRT) are effective for smoking cessation. After having received over-the-counter (OTC) status in Germany, concerns grew about effectiveness, increased risks, especially of adverse cardiovascular reactions, and inappropriate use of NRT. Thus, a pharmacy-based cohort study was launched. OBJECTIVES. To assess effectiveness, safety and appropriateness of use of an OTC nicotine patch (Nicotinell, Novartis Ltd.). Every customer who bought an OTC Nicotinell patch was eligible. All data were collected by self-administered questionnaires at weeks 2, 4, 8, 12 and 24 after inclusion. Six hundred and thirty-three customers were admitted, median duration of smoking was 19 years. Of the participants, 6% smoked up to 10 cigarettes per day, 43.6% between 11 and 20, 34.3% between 21 and 30, and 16.1% more than 30 cigarettes. Twenty-four weeks later, 351 participants replied: 28% (177 of 633) had quit smoking completely. Considering replies only the proportion of complete responders raised to 50.4%. There were no serious adverse events reported; 62.9% complied with the directions for use and did not use the patch for more than 3 months. About 45% smoked simultaneously with NRT. Pharmacy-based cohort studies are feasible. This study indicates that the nicotine patch is effective and safe in an OTC setting. There is still room to improve compliance with the directions for use.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12898081&dopt=Abstract [PubMed - as supplied by publisher]

Exp Brain Res. 2003 Jul 26 [Epub ahead of print].
Nicotinic effects on excitatory field potentials recorded from the immature CA3 area of rat hippocampal slices.

Psarropoulou C, Boivin M, Laudadio MA.

Ste-Justine Hospital Research Center, Department of Pediatrics, Universite de Montreal, 3175 Cote-Ste-Catherine, H3T 1C5, Montreal, QC, Canada.

We investigated the nicotinic modulation of the excitatory field potentials recorded from the immature (postnatal day 10-20) hippocampal CA3 area, in the presence of the GABA(A) antagonist bicuculline methiodide (BMI, 10 microM). Nicotine (50 microM) enhanced the evoked field potentials; its effects were also observed in the presence of the GABA(B) antagonist 2-hydroxy-saclofen (250 microM; added to BMI) and were blocked by pre-perfusion with the nicotinic antagonist hexamethonium (HXM, 50 microM). The potentiating effects of nicotine in BMI persisted during prolonged perfusion (more than 20 min), while those in control perfusion medium were transient. The nicotinic antagonists HXM (50 microM), methyllycaconitine (MLA, 0.01 microM) and dihydro-beta-erythroidine (DHbetaE, 50 microM) potentiated CA3-evoked field potentials. Perfusion of HXM in the presence of the anticholinesterase eserine (1 microM) or the muscarinic antagonist atropine (1 microM) did not alter its effects. None of the nicotinic agents tested changed the frequency of spontaneous BMI-induced epileptiform discharges (nicotine, HXM, MLA, DhbetaE), suggesting that nicotinic receptors do not drive spontaneous epileptiform discharges in this in vitro model. These experiments demonstrate that nicotinic receptors are activated tonically during disinhibition and modulate the activity of excitatory synapses in the immature CA3 hippocampal area. The persistent nicotinic facilitatory effects during disinhibition versus the transient in control conditions indicate that nicotinic modulation depends on environmental conditions and also that nicotinic receptors may be a contributing factor in early-life seizures.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12898092&dopt=Abstract [PubMed - as supplied by publisher]

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