The effects of micronutrient supplementation on vasomotor symptoms in postmenopausal women.

OBJECTIVE: Estrogen is the most effective treatment for vasomotor symptoms. Given its potential risks, herbal preparations and nutritional supplements have been developed as alternative remedies. The main aim of this double-blind, randomized, placebo-controlled trial was to assess any impact of a nutritional supplement containing 12 vitamins and nine minerals on the frequency and severity of hot flushes in postmenopausal women over a 3-month period. SUBJECTS AND METHODS: Ninety-one postmenopausal women were randomized to either the placebo (n = 45) or the treatment arm (n = 46). Seventy out of the 91 women completed the study (36 from the treatment group and 34 from the placebo group). At baseline and the 14-week post-intervention assessments, study participants completed questionnaires on the frequency and severity of hot flushes and night sweats, the Profile of Mood State questionnaire, the World Health Organization Quality of Life Questionnaire, the National Adult Reading Test and the Rey Auditory-Verbal Learning Test. Between assessments, the women also completed hot flush diaries. RESULTS: There was a significant decrease (p < 0.01) in the number (±standard error of the mean) of hot flushes experienced per week for treatment (pre 31.3 ± 4.7; post 23.1 ± 4.8) and placebo groups (pre 28.1 ± 4.7; post 17.3 ± 4.0). A significant decrease (p < 0.001) in the number of night sweats experienced per week was also observed in the treatment (pre 6.1 ± 1.0; post 4.2 ± 0.7) and placebo groups (pre 5.9 ± 0.7; post 3.7 ± 0.7). CONCLUSIONS: This study demonstrates a significant placebo effect on hot flushes and night sweats, as consistent with other studies. The micronutrient supplement containing 21 vitamins and minerals was not superior over placebo in effects on hot flushes and night sweat experiences.

A role for glutamate in subjective response to smoking and its action on inhibitory control.

RATIONALE: Our previous study using memantine in smokers suggests that there may be a differential role for N-methyl-D-aspartate (NMDA) receptors in the subjective and cognitive effects of smoking. OBJECTIVES: This study was designed to investigate if D-cycloserine (DCS) would modulate the subjective and cognitive effects of limited smoking. METHODS: Forty-eight habitual smokers abstinent for a minimum of 2 h were randomly allocated to receive either placebo or 50 mg DCS (double-blind) and were subsequently required either to smoke half of one cigarette or to remain abstinent. Subjective and physiological effects of DCS were measured at baseline, 90 min postcapsule, and again after the partial-smoking manipulation, while the effects on sustained attention (rapid visual information processing test--RVIP) and cognitive flexibility (intra-extra dimensional set-shift test--IED) were evaluated only after the partial-smoking manipulation. RESULTS: DCS alone did not produce significant subjective effects other than an increase in ratings of "Stimulated". In combination with partial smoking, however, DCS blocked the smoking-induced increase in "Stimulated" and the decrease in "Relaxed" ratings. Furthermore, in combination with smoking, DCS reduced the number of false alarms during the RVIP test (an index of inhibitory control) and produced a small increase in diastolic blood pressure. DCS failed to modulate IED performance. CONCLUSIONS: These findings provide further evidence of a role for glutamate release in the subjective effects of smoking but not the effects on attention and cognitive flexibility. Furthermore, our results indicate that glutamate release may also be involved in the effect of smoking on inhibitory control.

Degree of dependence influences the effect of smoking on cognitive flexibility.

Pre-frontal cortical (PFC) dysfunction has been put forward as the basis for development and maintenance of addiction. To explore this relationship, the present study investigated the effects of smoking on PFC-mediated cognitive flexibility and subjective states in low- (LD) and high-dependent (HD) smokers. Twenty-four LD and 24 HD smokers (Fagerström dependence scores ≤ 4 and ≥ 5, respectively) were randomly allocated to non-smoking or smoking condition (12 LD and 12 HD participants per condition). After abstaining from smoking for a minimum of two hours volunteers completed a battery of questionnaires [nicotine-specific Visual Analogue Scales (Nic-VAS), Questionnaire of Smoking Urges (QSU) and Profile of Mood States (POMS)] at baseline [T1] and again after smoking one cigarette or remaining abstinent [T2]. Cognitive flexibility was evaluated at T2 using the Intra-Extra Dimensional Set-Shift test. The Rapid Visual Information Processing test was performed as a control nicotine-sensitive task at several time points during the experiment. Compared to LD smokers, HD smokers had higher salivary cotinine and breath CO levels at baseline and reported more craving (QSU) and felt less stimulated (Nic-VAS), vigorous, friendly and elated (POMS) throughout the experiment. Smoking increased Nic-VAS ratings of 'Buzzed' and 'Dizzy' and decreased craving in all participants. Smoking selectively impaired cognitive flexibility in HD smokers since HD smokers allocated to the smoking condition made significantly more errors with the intra-dimensional set-shift than their counterparts in the abstinent condition. No effect of smoking on RVIP test was observed, most likely due to the practice effect which was significant in both groups of smokers. The practice effect, however, was more pronounced in LD smokers. This study demonstrates that PFC-mediated cognitive effects of smoking as well as subjective reports vary according to the degree of nicotine dependence.

Differential involvement of glutamatergic mechanisms in the cognitive and subjective effects of smoking.

There is growing preclinical evidence for the involvement of glutamate in the behavioral actions of nicotine. The aim of this study, was to investigate the role of N-methyl-D-aspartate (NMDA) receptors in the cognitive and subjective effects of smoking in humans. Sixty regular smokers took part in this double-blind placebo controlled study, that investigated the effect of the NMDA-antagonist memantine (40 mg) and the nicotinic-receptor antagonist mecamylamine (10 mg) on smoking-induced improvement in performance of a task of sustained attention and on smoking-induced changes in subjective effects and craving. Increases in subjective ratings of 'buzzed' following smoking were reversed by memantine, but not by mecamylamine. In contrast, improvement on a Rapid Visual Information Processing task by smoking was opposed by mecamylamine, but not by memantine. Smoking reduced craving for cigarettes, but neither drug altered this effect. Our results suggest that glutamatergic mechanisms may have differential involvement in the subjective and cognitive actions of smoking. Further investigations using different ligands are warranted to fully characterize the role of glutamate underlying the consequences of smoking behavior.

Effects of stress on emotional reactivity in hostile heavy social drinkers following dietary tryptophan enhancement.

AIM: Because individuals high on hostility may be at risk for alcohol abuse due to serotonergic dysfunction and greater reactivity to stress, we examined the effects of acute dietary tryptophan enhancement and stress on mood and craving for alcohol in low-hostile (LoH) and high-hostile (HiH) individuals. METHODS: Thirty-four LoH and 33 HiH heavy social drinkers [selection based on the Hostility scale from the Buss and Perry Aggression Questionnaire (1992)] received either tryptophan-enriched or control diet and underwent a stress-induction procedure. Trait differences between the two hostile groups were explored using personality, anxiety, and depression questionnaires. Mood, craving for alcohol, and salivary cortisol levels (CORT) were measured before and after tryptophan and after stress-induction. Heart rate (HR) was measured during stress-induction. RESULTS: HiHs compared to LoHs scored higher on the depression and anxiety trait scales as well in the character dimension Harm Avoidance and reported more of stress exposure over the past month. They also showed more negative mood and higher craving for alcohol. Diet alone did not produce any subjective or physiological effects. Stress increased CORT, HR, negative mood, and craving for alcohol. HiHs displayed higher CORT increase and lower cardiovascular reactivity in response to stress compared to LoHs. Opposite to the predictions, tryptophan enhancement selectively facilitated stress-induced increase in craving in the HiHs. CONCLUSION: Among heavy drinkers HiHs report higher craving for alcohol and show greater reactivity to stress as measured by CORT and negative mood. The effects of stress on craving in HiHs may be mediated by a serotonergic mechanism.

Gender specific effects of a mild stressor on alcohol cue reactivity in heavy social drinkers.

RATIONALE: Stress plays an important role in the development and maintenance of alcohol-abuse. Some of the effects of stress on alcohol-related behaviours, however, appear to be gender-dependent. AIM: The present study set out to examine the effects of stress on feelings of desire for alcohol, skin conductance response and alcohol consumption in the presence of alcohol-related cues in relation to gender. Participants were heavy non-dependent alcohol drinkers. METHODS: Thirty-two (16 males) participants drinking more than 21 units of alcohol per week were randomly allocated to undergo the experimental stress (based on the 'Trier Social Stress' Test) or the non-stress procedure before the alcohol cue exposure procedure, during which participants handled and smelled their preferred drink. Mood and saliva cortisol level changes were used as indices of the stress effects, while alcohol craving, skin conductance and alcohol consumption were the cue reactivity measures. RESULTS: Self ratings of anxiety and tension increased and cortisol levels remained high in the stress compared to the non-stress condition; no gender differences were found. Stress induced gender-specific effects with regard to skin conductance response and alcohol consumption measurements. Stressed females did not show an increase from baseline in the skin conductance response during the alcohol cue-exposure session, which was observed in the non-stressed females; they also consumed less alcohol than males under stress. CONCLUSION: Female participants respond less to alcohol-related cues when in a negative mood state. Such a finding suggests that females when in a negative mood may be less sensitive to positive incentive processes mediating cue reactivity compared to males.

Expression of flavour preferences conditioned by caffeine is dependent on caffeine deprivation state.

RATIONALE: The acquisition of a caffeine conditioned flavour preference depends on the caffeine deprivation status of subjects during conditioning. It is not known if the expression of an established flavour preference is also state-dependent. OBJECTIVES: To determine if the expression of a flavour preference conditioned by caffeine is dependent on the level of deprivation at the time of testing. METHODS: In a double-blind placebo controlled study, 44 subjects were given 4 days exposure to a novel flavoured drink following overnight abstinence from caffeine. Half the subjects received caffeine (100 mg) in the drink, while the remainder had placebo (maltodextrin, 100 mg). Subjects rated the pleasantness of the drink each time. On a fifth (test) day, the subjects were given additional caffeine (100 mg) or placebo 2 h before consuming and rating the pleasantness of the drink. RESULTS: Pleasantness ratings for the novel drink increased over the 4 conditioning days in subjects receiving caffeine, but decreased in those given placebo. On day 5, subjects who were trained and tested in the same caffeine deprivation state expressed pleasantness ratings similar to those for the final training day. In contrast, subjects who were trained and tested in different states expressed pleasantness ratings that were significantly different from those of the final training day. CONCLUSIONS: These results suggest that the expression of caffeine conditioned flavour preferences are acutely sensitive to current motivational state, and a number of possible explanations are discussed.

Alcohol and the appetizer effect.

In order to evaluate the effects of alcohol on appetite, 12 unrestrained and 10 restrained men ate lunch 20 min after consuming preloads consisting of water, an alcoholic fruit juice (alcohol) and a non-alcoholic fruit juice (juice). The unrestrained men ate significantly less after the juice preload, and ate most after alcohol. Intake was not altered significantly in the restrained men. However, both the alcohol and juice preloads reduced rated hunger and increased fullness, relative to the water control, in both restrained and unrestrained men. When the relationship between rated appetite and intake within the test meal was modelled mathematically, it was found that hunger increased more during the initial stages of the test meal in the unrestrained men who had consumed alcohol than in any other condition. No such effects were seen in the restrained subjects. Overall, these results suggest that alcohol has a complex action on appetite, which includes some form of appetite stimulation, and this may explain the excess energy intake reported previously in moderate alcohol consumers.

Transient hemorrhagic diathesis associated with an inhibitor of prothrombin with lupus anticoagulant in a 1 1/2-year-old girl: report of a case and review of the literature.

Acquired inhibitors of coagulation causing bleeding manifestations are rare in children, particularly without an associated underlying disorder such as autoimmune disease. We describe an otherwise healthy 1 1/2-year-old girl who had extensive spontaneous bruising and prolonged bleeding from venipuncture sites. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were prolonged, with evidence of an immediate-acting inhibitor. Thrombin clotting time, fibrinogen, and platelets were normal. Biologic assay of factors II, V, VII, and X were all low, with increasing values at higher dilutions. However, by immunoassay and/or chromogenic assays, only factor II was reduced. An antibody which failed to neutralize prothrombin activity in vitro was detected against radiolabeled prothrombin. Coagulation studies normalized in parallel with clinical recovery and disappearance of the antibody. This case demonstrates acute hypoprothrombinemia-lupus anticoagulant syndrome as a rare presentation of bleeding diathesis in a healthy young child.

Inhibitory effect of sandostatin on secretion of luteinising hormone and ovarian steroids in polycystic ovary syndrome.

Hyperinsulinism accompanies the raised luteinising hormone (LH) concentrations in women with the polycystic ovary syndrome (PCOS). Somatostatin inhibits insulin and LH secretion in healthy adults, so the effect of treatment with a long-acting somatostatin analogue ('Sandostatin') on gonadotropin and androgen secretion in PCOS was investigated. LH pulsatility, androgen concentrations, and hormonal responses to an oral glucose load and to administration of a GnRH agonist (buserelin) were measured before and after 7 days' treatment with sandostatin 100 micrograms subcutaneously twice a day in 10 amenorrhoeic women with classic features of PCOS. Sandostatin significantly reduced integrated LH concentrations and LH pulse amplitudes, oestradiol, testosterone, and androstenedione concentrations, and LH responses to buserelin; it also suppressed insulin and C-peptide responses to an oral glucose load. Thus sandostatin inhibits pituitary and ovarian hormonal responses in part by a direct influence on pituitary activity, and the possibility of an indirect effect mediated by changes in insulin concentrations requires investigation. These findings have implications for the treatment of infertility in women with PCOS.