Genomic affinities between maize and Zea perennis using classical and molecular cytogenetic methods (GISH-FISH).

In this study we have analysed and compared the genomic composition, meiotic behaviour, and meiotic affinities of Zea perennis and Zea mays ssp. mays. To do so we studied the parental taxa and the interspecific hybrid Zea perennis x Zea mays ssp. mays, using classical cytogenetic methods, as well as GISH and FISH. GISH enabled us to recognize the genomic source of each chromosome involved in the meiotic configurations of this hybrid, and established the genomic affinities between their parental species. The results obtained here reinforce the hypothesis of the amphiploid origin of Zea perennis and, together with previous research, indicate that the chromosomes with divergent repetitive sequences in maize and Zea luxurians could be the remnants of a relict parental genome not shared with Zea perennis.

The genome organization and diversification of maize and its allied species revisited: evidences from classical and FISH-GISH cytogenetic analysis.

The present review summarizes our classical and molecular cytogenetic investigations in the genus Zea. The results obtained from the meiotic behavior analysis of Zea species and hybrids, confirm the amphiploid nature of all species in the genus, with a basic number of x = 5 chromosomes. All species with 2n = 20 are diploidized allotetraploids, whereas Z. perennis (2n = 40) is an allooctoploid with four genomes somewhat divergent from one another. These analyses also revealed the existence of postzygotic reproductive isolation among Zea species. Our studies using genomic in situ hybridization (GISH) provide evidence about the evolutionary relationships among maize and its allied species, and reveal remarkable genomic divergences. Particularly, knob sequences were not completely shared between taxa previously considered to be closely related. Our data strongly suggest that the teosinte Z. mays parviglumis is not the only progenitor of cultivated maize. Introgression of Tripsacum into cultivated maize cannot be discarded.

GISHGenomic in situ hybridization reveals cryptic genetic differences between maize and its putative wild progenitor Zea mays subsp. parviglumis.

The aim of this paper is to test with genomic in situ hybridization the genomic affinities between maize and its putative progenitor Zea mays subsp. parviglumis. Blocking procedures were applied for the purpose of improving discrimination among chromosome regions. Unlabeled genomic DNA from Z. mays subsp. parviglumis as a blocking agent and labeled genomic DNA from maize were hybridized on maize chromosomes. On the other hand, mitotic metaphases from Z. mays subsp. parviglumis were blocked with unlabeled genomic DNA of maize and hybridized with labeled genomic DNA from Z. mays subsp. parviglumis. Both experiments showed that either maize or Z. mays subsp. parviglumis chromosomes have their own unique sequences. This means an unexpected degree of divergence if Z. mays subsp. parviglumis is the only progenitor of maize, a result that is discussed in relation to our previous genomic in situ hybridization observations and to the different scenarios proposed about the origin of maize.

The role of selective serotonin reuptake inhibitors in reducing alcohol consumption.

Preclinical and clinical studies demonstrated an inverse relationship between serotonergic activity and alcohol consumption. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine, citalopram, and fluvoxamine have subsequently been examined for their ability to reduce alcohol consumption in alcoholic subjects. Interindividual variability in response to SSRIs is large, with reductions in alcohol consumption ranging from 10% to more than 70%. Several factors, including gender, alcoholic subtype, and extent of drinking, appear to affect the treatment efficacy of the SSRIs. A significant challenge for researchers is to identify the subject variables that predict treatment response, providing a basis for guiding alcohol-dependent individuals to the treatment that is most likely to be effective for them. This article reviews the available clinical studies, discusses possible mechanisms of action for the SSRIs, and describes a model for predicting treatment responses in alcoholic subjects.

Review of pharmacokinetic and pharmacodynamic interaction studies with citalopram.

Citalopram is a selective serotonin reuptake inhibitor that is N-demethylated to N-desmethylcitalopram partially by CYP2C19 and partially by CYP3A4 and N-desmethylcitalopram is further N-demethylated by CYP2D6 to the likewise inactive metabolite di-desmethylcitalopram. The two metabolites are not active. The fact that citalopram is metabolised by more than one CYP means that inhibition of its biotransformation by other drugs is less likely. Besides citalopram has a wide margin of safety, so even if there was a considerable change in serum concentration then this would most likely not be of clinical importance. In vitro citalopram does not inhibit CYP or does so only very moderately. A number of studies in healthy subjects and patients have confirmed, that this also holds true in vivo. Thus no change in pharmacokinetics or only very small changes were observed when citalopram was given with CYP1A2 substrates (clozapine and therophylline), CYP2C9 (warfarin), CYP2C19 (imipramine and mephenytoin), CYP2D6 (sparteine, imipramine and amitriptyline) and CYP3A4 (carbamazepine and triazolam). At the pharmacodynamic level there have been a few documented cases of serotonin syndrome with citalopram and moclobemide and buspirone. It is concluded that citalopram is neither the source nor the cause of clinically important drug-drug interactions.

The role of the brain reward system in depression.

The goal of this review is to familiarize the reader about the potential involvement of the brain reward system (BRS) in symptoms of Major Depressive Disorder (MDD). The authors introduce a novel approach to study the pathophysiology of MDD that includes pharmacological probing of BRS pathways (e.g. d-amphetamine, hydromorphone) together with an elicited and measurable behavioral component (e.g. pleasant effects, increased energy, altered cognition). To this date, the major focus of MDD pathophysiology studies has been to characterize biological differences between healthy subjects and depressed patients such as alteration in the monoaminergic and endocrine systems. The relative importance of the various biological changes has not been elucidated, that is, linking these with specific behavioral manifestations in MDD have rarely been attempted. One core symptom of MDD is a decreased experience of pleasure or interest in previously enjoyed activities (i.e. anhedonia) such as work or hobbies, and is accompanied by decreased motivation or drive. The BRS consists of the neural pathways involved in eliciting rewarding experiences in animals and humans. The hypothesis is that altered BRS function may be an underlying brain mechanism of the loss of pleasure/interest experienced in MDD, and will be manifested through an altered response to a BRS probe. The authors have examined BRS function in MDD by introducing a pharmacological probe (i.e. d-amphetamine/d-amph). Amphetamine is defined as a probe due to its ability to release dopamine within major components of the BRS (i.e. the mesocorticolimbic dopamine system.) In addition to the objective pharmacological effects (e.g. altered heart rate), BRS probes like d-amph elicit reliable and measurable behavior, that is, the hedonic effects. A review of the neurobiology of MDD, the BRS, the rationale for implicating the BRS in depressive symptoms, and preliminary data, are presented in this article.

Probing peripheral and central cholinergic system responses.

OBJECTIVE: The pharmacological response to drugs that act on the cholinergic system of the iris has been used to predict deficits in central cholinergic functioning due to diseases such as Alzheimer's disease, yet correlations between central and peripheral responses have not been properly studied. This study assessed the effect of normal aging on (1) the tropicamide-induced increase in pupil diameter, and (2) the reversal of this effect with pilocarpine. Scopolamine was used as a positive control to detect age-dependent changes in central cholinergic functioning in the elderly. DESIGN: Randomized double-blind controlled trial. PARTICIPANTS: Ten healthy elderly (mean age 70) and 9 young (mean age 33) volunteers. INTERVENTIONS: Pupil diameter was monitored using a computerized infrared pupillometer over 4 hours. The study involved 4 sessions. In 1 session, tropicamide (20 microL, 0.01%) was administered to one eye and placebo to the other. In another session, tropicamide (20 microL, 0.01%) was administered to both eyes, followed 23 minutes later by the application of pilocarpine (20 microL, 0.1%) to one eye and placebo to the other. All eye drops were given in a randomized order. In 2 separate sessions, a single dose of scopolamine (0.5 mg, intravenously) or placebo was administered, and the effects on word recall were measured using the Buschke Selective Reminding Test over 2 hours. OUTCOME MEASURES: Pupil size at time points after administration of tropicamide and pilocarpine; scopolamine-induced impairment in word recall. RESULTS: There was no significant difference between elderly and young volunteers in pupillary response to tropicamide at any time point (p > 0.05). The elderly group had a significantly greater pilocarpine-induced net decrease in pupil size 85, 125, 165 and 215 minutes after administration, compared with the young group (p < 0.05). Compared with the young group, the elderly group had greater scopolamine-induced impairment in word recall 60, 90 and 120 minutes after administration (p < 0.05). CONCLUSION: There is an age-related pupillary response to pilocarpine that is not found with tropicamide. Thus, pilocarpine may be useful to assess variations in central cholinergic function in elderly patients.

Variations in response to citalopram in men and women with alcohol dependence.

OBJECTIVE: To examine the differential effects of citalopram on alcohol consumption in nondepressed women and men with mild to moderate alcohol dependence. DESIGN: Prospective, placebo-controlled study. PARTICIPANTS: Sixty-one subjects (34 men and 27 women). INTERVENTIONS: After a 2-week baseline, subjects were randomly assigned to 12 weeks of citalopram (40 mg per day) (n = 15 women, 16 men) or placebo (n = 12 women, 18 men). All received brief standard psychosocial interventions. OUTCOME MEASURES: Alcohol Dependence Scale, Montgomery-Asberg Depression Scale, Michigan Alcohol Screening Test, State-Trait Anxiety Inventory and daily alcohol intake. RESULTS: Pretreatment sex differences were evident in alcohol consumption, alcohol dependence, alcohol-related problems and on anxiety and depression measures. After treatment, analyses of covariance with depression and anxiety scores as covariates revealed a differential benefit of citalopram for men. Men receiving citalopram reduced average drinks per day by 44%, whereas women exhibited a 27% decrease (p < 0.05). CONCLUSIONS: Men may benefit more than women from citalopram in the treatment of alcohol dependence. These findings highlight the importance of examining sex as a significant variable in evaluating response to pharmacotherapy.

Dose-response evaluation of the interaction between sertraline and alprazolam in vivo.

In vitro data show the inhibition of alprazolam metabolism by sertraline via CYP3A4; therefore, using a randomized, double-blind, placebo-controlled design, the authors conducted this study to assess the potential for similar in vivo inhibition in humans. Ten healthy volunteers participated in two test sessions (placebo/alprazolam 1 mg orally) before the initiation of sertraline treatment. Blood samples were obtained over a 32-hour period and pharmacodynamic measures (sedation, psychomotor performance, memory function) were obtained over an 8-hour period. After a minimum of 2 weeks of daily sertraline self-administration (50, 100, or 150 mg/day), test sessions were repeated. Alprazolam concentrations (N = 6, 4, and 6 at sertraline doses of 50, 100, and 150 mg/day, respectively) showed no significant changes based on peak concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (t1/2[beta]), and area under the concentration-time curve (AUC(0-8)), with the exception of a reduced Cmax in the 50 mg/day group. Similarly, dynamic data showed no significant variations based on peak effect, Tmax, and AUC(0-infinity), with the exception of increased peak impairment in one measure of psychomotor performance. No differences were detected between placebo alone and placebo plus sertraline. These findings suggest that sertraline (50-150 mg/day) does not alter the single-dose kinetics or dynamics of alprazolam; therefore, the combination may be prescribed without an increased risk of alprazolam toxicity.

The effectiveness of antidepressants in elderly depressed outpatients: a prospective case series study.

BACKGROUND: This study examined the effectiveness of antidepressants in a group of elderly depressed outpatients by assessing depression prevalence and recording adverse events over time. METHOD: A prospective practice-based observational study (1991-1994) included consecutive outpatients at least 65 years of age with a DSM-III-R diagnosis of major affective disorder and who were prescribed antidepressant medications. Depressive symptoms were examined over time (stage 1 = 0 to 2 months; stage 2 = 2 to 6 months; stage 3 = 6 months to 2 years) with the Montgomery-Asberg Depression Rating Scale (MADRS). The cutoff scores of MADRS <18 and MADRS > or =18 were used in survival statistics. Adverse events were recorded systematically. RESULTS: A total of 213 patients were seen over 2677 visits (mean +/- SD age = 75.5+/-6.1 years). MADRS scores for 85.8% of patients declined to below 18 within the first 2 months of antidepressant treatment. MADRS scores were above 18 for 37.3% of patients after 6 months and for 37.1% after 2 years. The mean time to decline in MADRS scores to below 18 in stage 1 was 36.1 days, and there was a significant difference between the antidepressant classes (log rank = 8.3, df = 3, p = .04), with tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs)/reversible inhibitors of monoamine oxidase A (RIMAs) having shorter times to response. The mean time to reach scores above cutoff during stage 2 was 144.3 days (log rank = 5.7, df = 3, p = .13) and during stage 3, 538.6 days (log rank = 9.8, df = 3, p = .02). Patients receiving TCAs and MAOIs/RIMAs had longer durations of MADRS scores below cutoff during stage 3 than those taking atypical antidepressants and selective serotonin reuptake inhibitors. All antidepressant classes reported similar adverse event profiles. CONCLUSION: This study systematically examined antidepressant effectiveness in a prospective design. TCAs and MAOIs/RIMAs were shown to be superior in effectiveness during 2 of the 3 treatment stages.

Metabolic interactions of central nervous system medications and selective serotonin reuptake inhibitors.

Selective serotonin reuptake inhibitors (SSRIs) are prescribed alone and in combination with other psychotropic medications in the treatment of a variety of psychiatric disorders. Such combinations create the potential for pharmacokinetic interactions by affecting the activity of the cytochromes P450 (CYP450), drug metabolizing oxidative enzymes. SSRIs are not equivalent in their potential for interactions when combined with other central nervous system (CNS) medication. Generally citalopram and sertraline are characterized by weaker inhibition of CYP450 enzymes and, therefore, hold less potential for interaction than the other SSRIs. Paroxetine potently inhibits CYP2D6, which can result in increased neuroleptic serum concentrations, accompanied by increased CNS side-effects. Similarly, as a potent inhibitor of CYP2D6, fluoxetine can increase serum concentrations of neuroleptics and antidepressants and numerous case reports have documented concomitant adverse events. Fluoxetine also inhibits CYP3A and CYP2C19, increasing serum concentrations of some benzodiazepines. Fluvoxamine is a potent inhibitor of CYP1A2, a moderate inhibitor of CYP3A and a mild inhibitor of CYP2D6. Therefore, interactions with clozapine and benzodiazepines are evident.

Ritanserin in relapse prevention in abstinent alcoholics: results from a placebo-controlled double-blind international multicenter trial. Ritanserin in Alcoholism Work Group.

Ritanserin, a long-acting specific 5-HT2 receptor antagonist, revealed promising effects on alcohol intake behavior in both animal and preliminary human studies. To test its effectiveness in alcohol dependence this phase III clinical trial was initiated. In a placebo-controlled, randomized, double-blind international multicenter study 493 patients with moderate or severe alcohol dependence (DSM-III-R) were treated with three doses of ritanserin 2.5 mg/day (n = 122), 5 mg/day (n = 123), 10 mg/day (n = 126), or placebo (n = 122) over a period of 6 months. Ritanserin was well tolerated. The most frequent adverse experiences were headache and insomnia. A small increase in weight in the ritanserin-treated patients was observed. There were no significant differences between any dose of ritanserin and placebo in the relapse-rate, the time to relapse, craving for alcohol, or quantity and frequency of drinking after relapse. So far, neither ritanserin nor any other serotonergic medication has shown its specific effectiveness in relapse prevention in alcohol dependence.

Recommended drug treatment strategies for the alcoholic patient.

Significant progress has been made in the pharmacotherapy of alcoholism, specifically in the areas of withdrawal reaction, decreasing consumption, relapse prevention, and comorbid psychiatric illnesses. Psychosocial interventions are an important component of treatment strategies, and studies into the efficacy of medications often include psychotherapy or other nonpharmacological modalities. Increasingly, however, the evidence reveals the effectiveness of drug treatments for various components of the illness. Many different pharmacological agents and dosage regimens have been investigated for the treatment of the alcohol withdrawal syndrome. The effectiveness and simplicity of giving long-acting benzodiazepines, using a loading-dose technique, make this regimen first-line therapy. Both naltrexone (an opioid antagonist) and acamprosate (calcium acetylhomotaurinate) increase rates of abstinence and decrease relapse rates in alcohol-dependent individuals who are in abstinence-orientated programmes. If patients enter a comprehensive treatment programme, either naltrexone or acamprosate should be considered as an option in the treatment plan. The choice of medication is most likely to be determined by the availability of each, which differs considerably throughout the world. Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) seem to have short term effects, and are more effective in depressed alcoholics-dependent and in men. For all medications there is wide variability in treatment response (i.e. effect size) and compliance seems to be essential for successful treatment. Preliminary evidence suggests the usefulness of pharmacotherapy in treating alcohol dependence in the presence of other comorbid psychiatric illnesses. Antidepressants have shown efficacy in the treatment of alcoholism with comorbid depression, as has buspirone for the treatment of comorbid chronic anxiety symptoms. Further understanding of the neurobiological mechanisms of dependence in animals and humans as well as improved knowledge of predictors of treatment response will lead to improvements in the pharmacotherapy of alcohol dependence.

Efficacy and safety of neuroleptics in behavioral disorders associated with dementia.

BACKGROUND: Neuroleptics are commonly used to treat behavioral disorders associated with dementia. However, their safety and efficacy have not been well established in these patients. METHOD: A meta-analysis of randomized, controlled (either placebo or active drug), double-blind trials published since 1966 (N = 16; 499 treated, 112 active controls, and 123 placebo) was conducted. Data were collected on proportion of patients with clinically significant improvement, significant side effects, and dropout rates. RESULTS: Pooled mean percentages of patients who improved (95% CI): all neuroleptics, 64% (54% to 74%); low potency, 63% (54% to 72%); moderate potency, 70% (56% to 85%); moderate-high potency, 62% (49% to 75%); and high potency, 69% (49% to 90%). Thus, no differences in efficacy existed between different potencies of neuroleptics. Therapeutic effect (neuroleptic minus placebo) was only 26% (14% to 38%). Treatment-emergent side effects were more common for neuroleptics vs. placebo (mean difference = 25%, 13% to 37%), but pooled mean dropout rates were not different (mean difference = 4%, -7% to 14%). Neither weighting by clinical trial quality (3 raters; weighted agreement, 83% to 92%) nor exclusion of poor quality trials changed the results. CONCLUSION: Neuroleptics have small but significant efficacy over placebo in this population, and the efficacy rate is equivalent to the side effect rate. Comparing different neuroleptics shows they have similar efficacy, side effects, and dropout rates. Further study to determine more specific drug-responsive behaviors is needed to maximize benefits of these drugs.

Determinants of interindividual variability and extent of CYP2D6 and CYP1A2 inhibition by paroxetine and fluvoxamine in vivo.

Major depression may require antidepressant treatment for several years. This necessitates consideration of the long-term effects of antidepressants on multiple clinical endpoints. The antidepressants paroxetine and fluvoxamine are potent in vitro inhibitors of CYP2D6 and CYP1A2 isozymes, respectively. CYP2D6 and CYP1A2 are important for the clearance of 30 or more frequently used medications. Moreover, CYP1A2 also contributes to metabolism of 17beta-estradiol and metabolic activation of environmental procarcinogens (e.g., arylamines in cigarette smoke). The aim of this study was to assess the determinants of interindividual variability and extent of CYP2D6 and CYP1A2 inhibition during paroxetine and fluvoxamine treatment. Healthy volunteers and patients received caffeine (100 mg) and dextromethorphan (30 mg) at baseline and at steady state of paroxetine (10-20 mg/day, 5-74 days, N = 13) or fluvoxamine (50-100 mg/day, 5-43 days, N = 8). The caffeine metabolic ratio (CMR) and the log O-demethylation ratio (ODMR) of dextromethorphan in overnight urine were used as in vivo indices of the CYP1A2 and CYP2D6 isozyme activities, respectively. All subjects had an extensive metabolizer phenotype for CYP2D6. After fluvoxamine treatment, baseline CMR 5.1 +/- 1.4 (mean +/- SD) decreased to 2.7 +/- 1.1 (p < 0.01). Paroxetine did not have a significant effect on CMR (p > 0.05). In seven of eight subjects in the fluvoxamine group, posttreatment CMR was comparable with the minimum CMR value (2.0) attainable in nonsmoking healthy volunteers. After paroxetine treatment, log ODMR changed from a baseline value of -2.28 +/- 0.37 to -1.13 +/- 0.44, indicating significant inhibition of CYP2D6 (p < 0.001). Subjects' CYP2D6 phenotype did not change after paroxetine treatment. Fluvoxamine had no significant effect on log ODMR (p > 0.05). The extent of inhibition of CYP2D6 and CYP1A2 by paroxetine and fluvoxamine, respectively, displayed a positive correlation with baseline enzyme activity (p < 0.05). In addition, a negative association was found between the plasma paroxetine concentration and the CYP2D6 activity after paroxetine treatment (r = -0.47, p < 0.05). These data indicate that paroxetine and fluvoxamine treatment with minimum clinically effective doses significantly inhibit CYP2D6 and CYP1A2, respectively. The extent of inhibition of CYP2D6 by paroxetine and of CYP1A2 by fluvoxamine is dependent in part on the baseline enzyme activity. The interindividual variability in CYP2D6 inhibition by paroxetine can also be explained by variability in plasma paroxetine concentration. Most patients treated with fluvoxamine (50-100 mg/day) will reach population minimums for CYP1A2 activity. These results have potential implications for interindividual variability in the risk for drug-drug interactions mediated by CYP2D6 and CYP1A2 as well as for the disposition of 17beta-estradiol and environmental procarcinogens.

Safety of ipsapirone treatment compared with lorazepam: discontinuation effects.

OBJECTIVE: To determine discontinuation effects of ipsapirone, a novel azapirone and partial 5-HTIA agonist that has anxiolytic effects clinically and has not caused dependence or withdrawal symptoms in animals, and to compare these effects with those of the benzodiazepine lorazepam, owing to concern about dependence or withdrawal symptoms following use of these drugs. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Outpatient and inpatient treatment. PARTICIPANTS: Sixty-five healthy male volunteers who had experience with sedative-hypnotics or anxiolytics and did not meet DSM-III-R criteria for abuse or dependence. INTERVENTIONS: Participants were randomized to receive ipsapirone 15 mg per day (n = 17), ipsapirone 22.5 mg per day (n = 16), lorazepam 3 mg per day (n = 16), or placebo (n = 16) as outpatients for 36 days (treatment) followed by single-blind placebo as inpatients for 3 days and as outpatients for 6 days (withdrawal). OUTCOME MEASURES: Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Scale (HAM-D), Spielberger State Anxiety Scale, Sleep Quality Questionnaire, General Symptom Checklist, self-rated intoxication, Clinical Institute Withdrawal Assessment--Benzodiazepines (CIWA-Benzo), psychomotor testing and urine drug screen. RESULTS: Only 45 subjects completed the study; discontinuation rates did not significantly differ among treatment groups. At day 39, fewer and less severe symptoms (e.g., insomnia and fatigue) were found on the CIWA-Benzo scale after treatment with ipsapirone or placebo than after treatment with lorazepam (p < 0.05). Subjects reported longer sleep latency and poorer sleep quality after receiving lorazepam than after receiving ipsapirone or placebo. Scores on the HAM-D, Spielberger State Anxiety and HAM-A scales did not change from baseline. CONCLUSIONS: Withdrawal symptoms were detected after discontinuation of therapeutic doses of lorazepam. Significantly fewer symptoms were observed after withdrawal from anxiolytic doses of ipsapirone.

The extent and determinants of changes in CYP2D6 and CYP1A2 activities with therapeutic doses of sertraline.

The extent of changes in CYP2D6 and CYP1A2 activities with higher therapeutic dosages (>50 mg/day) of sertraline is not well established in vivo. This study assessed the extent and determinants of changes in CYP2D6 and CYP1A2 isozyme activities after treatment with clinically relevant doses of sertraline. Patients and healthy volunteers aged 19 to 85 years (N = 21) were treated with sertraline for 5 to 55 days. The dosage of sertraline ranged from 25 to 150 mg/day (93.5+/-26.4 mg/day; mean +/- SD). All subjects had an extensive metabolizer phenotype for CYP2D6 and received a single oral dose of dextromethorphan (30 mg) and caffeine (100 mg) before and after sertraline treatment. The log O-demethylation ratio (ODMR) of dextromethorphan and the caffeine metabolic ratio (CMR) in overnight urine were used as in vivo indices of the CYP2D6 and CYP1A2 isozyme activities, respectively. Concurrent medications and lifestyle habits (e.g., smoking and diet) were monitored during the study. Baseline log ODMR (-2.33+/-0.45) but not CMR (5.1+/-1.9) (mean +/- SD) significantly changed after sertraline treatment (-2.19+/-0.62; 4.5+/-1.6, respectively) (p: ODMR = 0.04, CMR = 0.10). There was no significant effect of age, dose, duration of treatment, gender, sertraline and/or desmethylsertraline plasma concentration, subject type (patient or volunteer), and weight on the extent of changes in log ODMR or CMR (p > 0.05). In conclusion, sertraline treatment at a mean daily dosage of 94.0 mg did not significantly change CYP1A2 activity and resulted in a modest inhibition of CYP2D6 activity.

Localization of the genes controlling B chromosome transmission rate in maize (Zea mays ssp. mays, Poaceae).

In previous papers we found that the frequency of B chromosomes in native races of maize varies considerably in different populations. Moreover, we found genotypes that control high and low transmission rates (TR) of B chromosomes in the Pisingallo race. In the present work crosses were made to determine whether the genes controlling B-TR are located on the normal chromosome set (As) or on the B chromosomes (Bs). We made female f.0B × male m.2B crosses between and within high (H) and low (L) B-TR groups. The Bs were transmitted on the male side in all cases. The mean B-TR from the progeny of f.0B (H) × m.2B (H) and f.0B (H) × m.2B (L) crosses was significantly higher than that from f.0B (L) × m.2B (L) and f.0B (L) × m.2B (H) crosses. The results show that the B-TR of the crosses corresponds to the H or L B-TR of the 0B female parents irrespective of the Bs of the male parent. This indicates that B-TR is genetically controlled by the 0B female parent and that these genes are located on the A chromosomes.