Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution.

Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ∼500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey whole-genome sequence and assembly. We note challenges faced owing to its high content of repetitive elements and GC bases, as well as the absence of broad-scale sequence information from closely related species. Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages. Moreover, the results help define key evolutionary events within vertebrate lineages, including the origin of myelin-associated proteins and the development of appendages. The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms.

Superparamagnetic iron oxide nanoparticle attachment on array of micro test tubes and microbeakers formed on p-type silicon substrate for biosensor applications.

A uniformly distributed array of micro test tubes and microbeakers is formed on a p-type silicon substrate with tunable cross-section and distance of separation by anodic etching of the silicon wafer in N, N-dimethylformamide and hydrofluoric acid, which essentially leads to the formation of macroporous silicon templates. A reasonable control over the dimensions of the structures could be achieved by tailoring the formation parameters, primarily the wafer resistivity. For a micro test tube, the cross-section (i.e., the pore size) as well as the distance of separation between two adjacent test tubes (i.e., inter-pore distance) is typically approximately 1 µm, whereas, for a microbeaker the pore size exceeds 1.5 µm and the inter-pore distance could be less than 100 nm. We successfully synthesized superparamagnetic iron oxide nanoparticles (SPIONs), with average particle size approximately 20 nm and attached them on the porous silicon chip surface as well as on the pore walls. Such SPION-coated arrays of micro test tubes and microbeakers are potential candidates for biosensors because of the biocompatibility of both silicon and SPIONs. As acquisition of data via microarray is an essential attribute of high throughput bio-sensing, the proposed nanostructured array may be a promising step in this direction.

Prophylactic effect of citalopram in unipolar, recurrent depression: placebo-controlled study of maintenance therapy.

BACKGROUND: Major depression is highly recurrent. Antidepressant maintenance treatment has proven efficacy against recurrent depression. AIMS: Comparison of prophylactic efficacy of citalopram versus placebo in unipolar, recurrent depression. METHODS: Patients 18-65 years of age with recurrent unipolar major depression (DSM-IV), a Montgomery-Asberg Depression Rating Scale score of > or =22 and two or more previous depressive episodes, one within the past 5 years, were treated openly with citalopram (20-60 mg) for 6-9 weeks and, if responding, continued for 16 weeks before being randomised to double-blind maintenance treatment with citalopram or placebo for 48-77 weeks. RESULTS: A total of 427 patients entered acute treatment and 269 were randomised to double-blind treatment. Time to recurrence was longer in patients taking citalopram than in patients taking placebo (P:<0.001). Prophylactic treatment was well tolerated. CONCLUSIONS: Citalopram (20, 40 and 60 mg) is effective in the prevention of depressive recurrences. Patients at risk should continue maintenance treatment at the dose necessary to resolve symptoms in the acute treatment phase.

A double-blind double-dummy study of citalopram comparing infusion versus oral administration.

BACKGROUND: This study compares antidepressant efficacy and tolerability of citalopram given either orally or as a slow drop infusion. METHODS: Citalopram (40 mg/day) was administered double-blindly as tablets or slow-drop infusion during the first 10 days and then open, orally, up to treatment Day 42. RESULTS: In 60 moderately to severely depressed patients, the Hamilton depression total score (17-items) at baseline was 23.9 and 23.6 in the active infusion (n = 30) and active tablet (n = 30) group, respectively. These scores dropped in both groups to 15.6 and 16.9 on Day 10, and to 10.3 and 10.2 on Day 42. Response rates (delta Hamilton > or = 50%) amounted to 33.3% and 17.9% on Day 10, and 66.2% and 63.3% on Day 42, without a relevant group difference in citalopram plasma concentration. CONCLUSION: Slow-drop infusion with citalopram shows a similar risk/benefit relationship to oral citalopram. The design of this study allowed us to evaluate pharmacological but not psychological factors which may contribute to response to slow-drop infusion.

Citalopram and viloxazine in the treatment of depression by means of slow drop infusion. A double-blind comparative trial.

Antidepressant efficacy and tolerability of citalopram and viloxazine were compared under double-blind conditions during the first two weeks of treatment with slow drop infusion, followed by oral administration for the rest of the six week trial period. The 62 severely depressed and hospitalised patients included in the intention-to-treat analysis had a mean age of 45 years (range 23 to 70 years). About two thirds of the patients were female. Thirty patients were allocated to the citalopram and 32 patients to the viloxazine group. The mean MADRS total score at baseline was 34 in both groups and decreased to 12.3 in the citalopram and to 16.9 in the viloxazine group after 14 days of infusion. On day 42 (end point) the scores dropped to 6.7 in the citalopram and to 13.1 in the viloxazine group respectively. The group differences reached the level of significance at both time points (p < 0.05) in favour of citalopram. The analysis of treatment emergent adverse events based on the UKU scale showed a higher frequency of nausea on day 14 and constipation at study end in the viloxazine group (p < 0.05) whereas reported weight gain (day 21) and concentration difficulty (day 21) were more frequently seen in the citalopram group (p < 0.05). Standard laboratory investigations and ECG analyses did not show clinically relevant abnormalities. It is concluded that antidepressant treatment with citalopram infusion followed by oral citalopram may be more efficacious than a corresponding treatment schedule with viloxazine.

Effect of sleep deprivation on neuroendocrine response to a serotonergic probe in healthy male subjects.

Neuroendocrine responses to stimulation with a selective serotonin reuptake inhibitor (citalopram) were measured to investigate the effects of all-night sleep deprivation on serotonergic function in healthy male subjects (n = 7). We studied citalopram-stimulated prolactin and cortisol plasma concentrations in a placebo-controlled cross-over protocol following sleep and sleep deprivation. Citalopram infusion (20 mg i.v. at 14:20-14:50 h) after a night of undisturbed sleep prompted robust increases in both plasma prolactin and cortisol concentrations. Following a night of sleep deprivation, by contrast, the citalopram-induced prolactin response was blunted, but the cortisol response was not significantly altered. This differential response pattern relates to the distinct pathways through which serotonin may activate the corticotrophic and the lactotrophic systems. While an unchanged cortisol response does not indicate (but also does not refute the possibility of) an altered serotonergic responsivity following sleep deprivation, the suppressed prolactin response could reflect a downregulation of 5-HT1A or 2 receptors. An alternative, not mutually exclusive, explanation points to the possibility that sleep deprivation activates the tubuloinfundibular dopaminergic system, the final inhibitory pathway of prolactin regulation.

A double-blind, placebo-controlled study of citalopram with and without lithium in the treatment of therapy-resistant depressive patients: a clinical, pharmacokinetic, and pharmacogenetic investigation.

Sixty-nine depressive patients (DSM III criteria: 296.2, 296.3, 296.5, 300.4) were treated with 40 to 60 mg citalopram (CIT) daily for 4 weeks. Among them, 45 responded to treatment (improvement > 50% on the 21-item Hamilton Rating Scale for Depression [HAM-D]) and continued their treatment for another week before being released from the study. The 24 nonresponders were randomized and comedicated under double-blind conditions with lithium carbonate (Li) (2 x 400 mg/day) (CIT-Li group) or with placebo (CIT-Pl group) from days 29 to 35. For days 36 to 42, the patients of both subgroups were treated openly with Li (800 mg/day) in addition to the ongoing CIT treatment. On day 35, 6 of 10 patients responded to the CIT-Li combination, whereas 2 of 14 patients only responded to the CIT-Pl combination. This group difference reached significance (p < 0.05) on day 35 with lower HAM-D total scores in the CIT-Li group. No evidence was seen of a pharmacokinetic interaction between CIT and Li, and this combination was well tolerated. Patients were phenotyped with dextromethorphan and mephenytoin at baseline and at day 28. As evaluated at baseline, three patients (responders) were poor metabolizers of dextromethorphan and six patients (three responders and three nonresponders) of mephenytoin. On day 28, the ratio CIT/N-desmethylCIT (DCIT) in plasma was significantly higher in poor than in extensive metabolizers of mephenytoin (p = 0.0001), and there was a significant positive correlation between the metabolic ratio of dextromethorphan and the ratio DCIT/N-didesmethylCIT in plasma (p < 0.001). These findings illustrate the role of CYP2D6 and CYP2C19 in the metabolism of CIT. It can be concluded that Li addition to CIT is effective in patients not responding to CIT alone without any evidence of an accentuation or provocation of adverse events.

[Validity of the Narcissism Inventory (Denecke and Hilgenstock)]. / Zur Validität des Narzissmusinventars (Denecke u. Hilgenstock).

For investigating the validity of the Narzissmusinventar 27 somatic and psychic healthy men aged between 30 and 45 were tested with the Narzissmusinventar, the Fragebogen zur Erfassung von Aggressivitätsfaktoren, the State-Trait-Angstinventar and the Fragebogen zur Messung der Kontrollambitionen. Moreover a structured interview for the evaluation of type A behavior was administered. Correlative statistical analyses showed in the sense of construct validity that the dimension of the "bedrohtes Selbst" ("threatened self") is characterized by anxiety, feelings of insufficiency and aggression. The other subscales of the Narzissmusinventar correlate only with a few variables of the other tests and the speaking behavior. These subscales evaluate the narcissistic personality traits which the other instruments we used in our investigation are not able to reflect.

Ischemic ECG changes are found more often in asymptomatic men with a coronary prone behaviour pattern.

Type A behaviour has been related to coronary heart disease (CHD) as an independent risk factor. Therefore, ischemic electrocardiographic (ECG) changes may be more prominent in Type A than in Type B individuals. ECG abnormalities were assessed by the Cardiac Infarction Injury Score (CIIS), which has predictive power for sudden death. In 100 healthy men aged 30-45 yr, the CIIS was related to cardiovascular risk factors such as age, blood pressure, smoking, family history of CHD and behaviour pattern groups defined by the Structured Interview (46 Type A, 20 Type X and 34 Type B subjects). The distribution of the CIIS was different among the behaviour pattern groups (p < 0.05) and was shifted towards higher ischemic scores in Type A subjects. These findings suggest that clinically asymptomatic persons with Type A behaviour have a greater probability of suffering ischemic heart disease and possible sudden death.

Comparison of light treatment with citalopram in winter depression: a longitudinal single case study.

A woman with seasonal affective disorder (SAD) remitted within a week in each of six separate trials of light therapy. She remitted within 2 weeks of initiating citalopram treatment. Light treatment in the morning advanced and improved sleep, whereas citalopram delayed sleep and induced intermittent awakenings. These opposite patterns suggest that sleep deprivation or sleep shifts were not crucial for eliciting therapeutic response. Light and citalopram both selectively reduced intake of sweet carbohydrate parallel with improvement, implicating CNS serotonergic mechanisms in the interaction of mood and food in winter.

The contributions of cigarette yield, consumption, inhalation and puffing behaviour to the prediction of smoke exposure.

The overall predictability of smoke exposure indicators and the importance of different influencing factors were assessed in a cross-sectional study (n = 144), using multiple linear regression and bivariate correlation analyses. Respiratory CO, and plasma nicotine and cotinine concentrations were measured before and after smoking, for lip or holder smoking, and natural or standardized (30 puffs) puffing. The prediction of smoke exposure measures varied considerably across sampling times, smoking conditions, and dependent variables. The variance of plasma cotinine and nicotine were predictable to a considerable extent (30%; 19-41%) by cigarette yield, consumption and self-reported inhalation, whereas respiratory CO was less predictable (15-27%). Generally, consumption was the most important predictor, surpassed by nicotine yield for post-smoking plasma nicotine. Smoke exposure from a single smoking period could be predicted to a variable degree (CO, 11-42%; nicotine, 33-54%) by a subset of smoker's sex, cigarette yield, self-reported inhalation and puffing characteristics. The highest prediction was found under standardized smoking conditions (30 puffs through a holder), the lowest under natural smoking conditions. The best subset of predictors, especially with respect to puffing parameters, was found to vary considerably across smoking conditions and dependent variables.

Ultralow-yield cigarettes and type of ventilation: the role of ventilation blocking.

Habitual smokers of perforation-ventilated cigarettes and of channel-ventilated cigarettes (18 male and 18 female subjects each; nicotine yield 0.1-0.3 mg, 0.2 mg, respectively) were compared with respect to different smoke exposure indicators and puffing behavior. The role of ventilation blocking was assessed by comparing normal lip contact with smoking through a cigarette holder. The presmoking concentrations (plasma nicotine, cotinine, respiratory CO) were higher for channel-filter than for perforation-ventilated cigarettes, as were the pre- to postsmoking boosts (nicotine, CO) with normal lip smoking. Holder smoking resulted in lower boosts than lip smoking for the channel filter cigarettes, although the puffing behavior was considerably intensified. The boosts for perforation-ventilated cigarettes remained unchanged and were reached with only moderately intensified puffing behavior. The results indicate the importance of ventilation blocking in everyday lip smoking for channel-filter cigarettes, but not for conventional, perforated cigarettes.

Nicotine yield as determinant of smoke exposure indicators and puffing behavior.

Relationships between machine smoking nicotine yield and different smoke exposure indicators were investigated in a cross-sectional study. For each of the four yield classes H (1.0-1.2 mg), M (0.7-0.9 mg), L (0.4-0.6 mg) and U (0.1-0.3 mg) 18 male and 18 female subjects were recruited. The experimental design (2 x 2) included smoking with lip contact or with a flowmeter holder, natural smoking of one cigarette or forced smoking (30 puffs). The analysis of presmoking measures revealed for plasma nicotine H greater than L, U; M greater than U, for plasma cotinine H, M greater than U, and no differences for respiratory CO. Pre- to postsmoking boosts of CO and nicotine increased with yield, but the differences were smaller than those in yield. This partial compensation can be attributed to puffing behavior as revealed by the differences between yield classes with respect to flowmeter measures (puff volume, flow parameters, number of puffs). Contact condition hardly influenced the results. Forced puffing revealed down regulation mechanisms in smoke absorption and, less pronounced, in puffing behavior. Cardiovascular and subjective effects were widely independent of yield. Plasma cotinine appeared as the best smoke exposure indicator, due both to its high retest reliability and its relationship to nicotine yield.

A psychopharmacological and psychophysiological evaluation of smoking motives.

Compared to alcohol or opiate dependence, the physical withdrawal symptoms which occur with the cessation of the tobacco smoking habit are relatively weak, although they can produce discomfort. Long-term abstinence rates, however, remain similarly low. This raises the question about the nature of the strength of this habit. When evaluating the complex mechanisms of cigarette smoking behavior and its determinants, a surprisingly large variety of pharmacological and nonpharmacological motives emerges. These appear to outweigh the health-related arguments for abstinence in the majority of smokers. An attempt has been made to categorize classes of motives according to their positive or negative reinforcing impacts on the habit. The acute tobacco withdrawal syndrome, problems with weight gain after cessation and the phenomenon of craving are classified as primarily negative reinforcers. Effects of smoking on cognitive functions and on "pleasure" are seen as primarily positive reinforcers. In conjunction with stress, the tranquillizing effects of smoking seem to have negative reinforcing properties in situations involving passive coping and anxiety, whereas smoking may have positive reinforcing effects in situations involving active coping. It is suggested that the memory of these reinforcing effects of smoking can contribute to the phenomenon of craving. Although substantially reduced after discontinuation of the smoking habit, craving may exacerbate and contribute significantly to late relapse.

Development of central and peripheral smoking effects over time.

The present study compared for the first morning cigarettes CO and nicotine absorption as well as the effects on EEG and peripheral functions across a period of 90 min. Eighteen smokers participated in two sessions, one in which they smoked two cigarettes in succession and another in which they smoked three cigarettes at 30-min intervals. Smoking two cigarettes in succession produced a particularly wide range in nicotine absorption so that the subjects could be grouped into high (HN) and low (LN) nicotine absorbers, differing significantly in their CO and nicotine absorption. The smoking-induced cardioacceleration was greater and lasted longer in the HN than in the LN group. While the dominant alpha frequency increased to a significant extent in the HN group only, beta power increased in both groups, alpha power remained unaffected, theta power decreased in the HN group only and the effects on heart rate, dominant alpha frequency and beta power were significantly correlated with nicotine absorption across both groups. Smoking three cigarettes at 30-min intervals produced qualitatively similar but generally smaller effects. However, neither nicotine uptake nor any of the physiological parameters showed differential developments between the two groups, except the dominant alpha frequency, which increased in the HN group only. The development of acute tolerance to smoking across three cigarettes was observed only for finger vasoconstriction, craving to smoke and sickness after smoking, but not for cardioacceleration or any EEG parameters.

Separate effects of cigarette smoke yield and smoke taste on smoking behavior.

The purpose of this experiment was to compare independently the influence of different cigarette smoke taste categories and different machine standard smoke yield values on cigarette smoking behavior and related subjective measures. In six separate sessions 15 regular smokers were presented with a medium and a low smoke yield cigarette of each of the three taste categories, mentholated, dark (Gauloises) and blond (Muratti) tobacco. Each session included a "natural" and a "forced" smoking procedure of one cigarette type only. Forced smoking consisted of smoking 30 puffs whereby a new half-length cigarette was presented after every third puff. During the seventh session, habitual brand cigarettes were smoked as a reference. The sessions followed in weekly intervals, and the subjects became familiar with the test cigarettes during the last 5 days preceding each test session. Although general acceptability of the cigarettes, smoking satisfaction and pleasantness of taste were clearly lower for all test cigarettes as opposed to the habitual brand reference cigarettes, these measures remained unaffected by taste or smoke yield of the test cigarettes. Harshness of smoke was higher in the dark tobacco category and generally decreased with the lower smoke yield cigarettes. Independent effects of taste and smoke yield were obtained for total puff volume, inhalation time and CO absorption, suggesting a compensatory intensification of smoking behavior for low yield cigarettes and an independent increase of smoking intensity from mentholated to dark tobacco to blond tobacco. The results suggest therefore that factors which affect cigarette smoke taste have effects on smoking behavior which are separate from those obtained by comparing smoke yields.

Can smoking increase attention in rapid information processing during noise? Electrocortical, physiological and behavioral effects.

This study investigated the effects of smoking on subject-paced visual rapid information processing performance (RIP) under the influence of disturbing noise. The RIP task required the subjects to detect triads of even or odd digits within a pseudorandom sequence of single digits presented on a screen. Two groups of 12 female habitual smokers who were not allowed to smoke during the last 10 h preceding the test sessions underwent two test sessions each consisting of two RIP trials separated by a smoking period (habitual cigarette) for one group and by a relaxation period without smoking for the second group. Noise disturbance was presented during the second RIP trial of one of the two sessions only. Smoking increased RIP performance, but noise failed to show any measurable effect. EEG analyzed during RIP revealed the expected noise-induced decrease in alpha power. ERP analyses showed a smoking-induced decrease in the CNV-related negativity but no noise effects. The late positive wave (LP) increased after smoking, but to a lesser extent under the noise condition. The analyses of peripheral physiological measures revealed smoking- and noise-induced heart rate acceleration and cutaneous vasoconstriction. Plasma cortisol, prolactin and HGH were also increased after the noise session. The results indicate therefore that smoking increased RIP, whereas noise failed to affect mental performance, although it produced measurable vegetative stress effects.