Smokers deprived of cigarettes for 72 h: effect of nicotine patches on craving and withdrawal

Abstract Rationale. Research on the effects of nicotine abstinence and nicotine replacement has not provided consistent information about the impact of replacement therapies on tobacco withdrawal and craving. Objective. This study investigated craving and withdrawal symptoms over a 72-h period of abstinence from cigarettes. Methods. Twenty-four healthy volunteers, not intending to quit smoking, were housed in an experimental unit during three 72-h conditions, consisting of either free smoking, enforced smoking cessation with nicotine replacement therapy (NRT) patches, or enforced smoking cessation with placebo patches. The conditions were adhered to using a randomized crossover design, each separated by at least 10 days of washout. Patches, administered in a double-blind fashion, were given as nicotine (21 mg/24 h) and placebo every 24 h. Self-reported cigarette craving and withdrawal were assessed using multi-item scales at fixed intervals over each condition period. Urinary and plasma cortisol levels were also assayed at fixed intervals over each period. Results. Craving intensity was significantly lower with free smoke than with placebo and with NRT patches than with placebo. No difference in craving levels was found between those who smoked or those who had NRT patches. Withdrawal symptoms were significantly lower with free smoke than with either placebo or NRT patches, but there was no difference in levels of withdrawal between those on NRT patches and those on placebo. During the placebo and NRT patch periods, craving intensity displayed a circadian rhythm, with craving levels lowest in the morning and peaking in the evening. Nicotine delivered via the patch had no impact on these circadian variations in craving. There was no evidence of systematic temporal variations in craving levels during the free smoking period. Conclusions. The data suggested that craving and withdrawal symptoms may be sustained by different physiological pathways, and that only selected components of cigarette craving are influenced by NRT. Electronic Publication     

Inhibition of matrix-proteases by polyphenols: chemical insights for anti-inflammatory and anti-invasion drug design

Flavanols--a class of plant polyphenols abundant in tea leaves and grape seeds and skins--have been found to inhibit some matrix-proteases instrumental in inflammation and cancer invasion, such as leukocyte elastase (LE) and gelatinases. In order to establish the relationship between chemical structure and activity, 27 different flavonoids (antocyanidins, dihydrochalcones, dihydroflavonols, flavanolignans, flavanols, flavones, flavonols and isoflavones) and other compounds with anti-oxidant properties were evaluated for their potential in blocking LE and gelatinase activities. LE activity was measured using a chromogenic substrate: from comparison of the different levels of inhibition, it was deduced that a crucial role in inhibition might be played by a galloyl moiety or hydroxyl group at C3, three hydroxyl groups at B ring, one hydroxyl group at C4', and a 2,3-double bond. Gelatinase activity was measured using the gelatin-zymography assay, and its inhibition showed that three hydroxyl groups at the A or B ring, or, for non-planar molecules, a galloyl moiety at C3 could be determinant. This comparative study is proposed as a basis for designing new molecules with enhanced anti-proteolytic activities, and no or reduced side-effects, for use in hindering inflammation, cancer invasion and angiogenesis.     

Effect of the amisulpride isomers on rat prolactinemia

The effects on rat serum prolactin level of the two isomers constituting the racemic form of amisulpride were compared. (S-)-amisulpride induced hyperprolactinemia at lower doses (ED(50) = 0.09 +/- 0.01 mg/kg) than racemic- (ED(50) = 0.24 +/- 0.03 mg/kg) and (R+)-amisulpride (ED(50) = 4.13 +/- 0.05 mg/kg), in accord with their affinities for pituitary dopamine D(2) receptor (K(i) = 3.8 +/- 0.2, 6.4 +/- 0.2 and 143.3 +/- 2.3 nM, respectively). At doses twice the ED(50), (S-)-amisulpride produced a maximal increase in prolactin level similar to that of the racemic form (403 +/- 21% and 425 +/- 15%, respectively), but higher than that of (R+)-amisulpride (198 +/- 8%). These results suggest that the hyperprolactinemia induced by the racemic-amisulpride is mostly due to its (S-)-isomer.     

Stimulation of serotonin1B receptors induces conditioned place aversion and facilitates cocaine place conditioning in rats

RATIONALE: Changes in serotonin(1B) (5-HT(1B)) receptor function appear to modify the reinforcing properties of cocaine, but the direction of this effect is not completely clear. Pharmacological stimulation of 5-HT(1B) enhanced the rewarding properties of self-administered cocaine while attenuating the threshold-reducing effect of cocaine in the intracerebral brain stimulation procedure. OBJECTIVE: The present study investigates how pharmacological modification of 5-HT(1B) receptor-mediated neurotransmission influence cocaine motivational properties in the conditioned place preference paradigm in rats. METHODS: In separate groups of rats the motivational properties of CP 94,253, a selective 5-HT(1B) agonist, or GR 127935, a 5-HT(1B/D) receptor partial agonist, given alone or in combination, were determined. To evaluate their influence on cocaine-induced place conditioning, CP 94,253, that was found to be aversive, was given every day before each conditioning session, while GR 127935, which given alone had no effect, was administered only before cocaine conditioning sessions. RESULTS: CP 94,253, injected IP at 2.5 and 10 (but not 0.5) mg/kg produced place aversion in the place conditioning paradigm. The aversive effect of 2.5 mg/kg CP 94,253 was completely reversed by 10 mg/kg SC GR 127935. Given before every conditioning session, CP 94,253 did not modify place conditioning by four injections of 10 mg/kg cocaine but at 2.5 mg/kg it potentiated a sub-threshold dose of cocaine. The place preference caused by these two drugs was completely reversed by 10 mg/kg GR 127935. The antagonism by GR 127935 of CP 94,253's effects was shown not to be due to the induction of state-dependent effects. CONCLUSION: The results suggest that stimulation of 5-HT(1B) receptors causes place aversion, and enhances the effect of low doses of cocaine in the conditioned place preference paradigm.     

Synthesis of variously substituted 1,8-naphthyridine derivatives and evaluation of their antimycobacterial activity

A series of 1,8-naphthyridine derivatives variously substituted in the 2, 3, 4 and 7 positions were synthesized for in vitro evaluation of antimycobacterial activity in accordance with an international program with the tuberculosis antimicrobial acquisition and coordinating facility (TAACF). Several compounds 4, 8, 12, 14, 19, 29 and 30, when tested at a concentration of 6.25 microg/ml against Mycobacterium tuberculosis H37Rv, showed an interesting activity with % inhibition in the range 38-96%. The most effective substituent in position 2, 4 or 7 of the 1,8-naphthyridine nucleus seem to be the piperidinyl group.     

Antioxidant properties of MDL and MMDL,two nicergoline metabolites,during chronic administration of haloperidol

We evaluated the effects of 10-alpha-methoxy-9,10-dihydrolysergol (MDL) and 1-methyl-10-alpha-methoxy-9,10-dihydrolysergol (MMDL), two nicergoline metabolites, during chronic treatment with haloperidol in rats. Haloperidol induced a significant decrease in the glutathione (GSH) content in selected areas of the brain and in the liver. Prolonged administration of MDL, MMDL or nicergoline antagonized the haloperidol-induced GSH decrease. Lipid peroxidation in the cortex and striatum was suppressed by MDL, MMDL or nicergoline administration. Our results show that MDL, MMDL and nicergoline have antioxidant activity, preventing not only GSH depletion but also lipid peroxidation. These observations suggest beneficial properties of MDL and MMDL in the treatment of neuroleptic-induced side effects.     

The incidence of varicella: correction of a common error

BACKGROUND: Interest in the incidence of varicella (chickenpox) has increased since the discovery of an effective vaccine, but calculations to date have incorrectedly ignored the question of susceptibility. METHODS: We studied the occurrence of varicella in Italy on the basis of 33,343 children (age 0-14 years) cared for by 35 pediatricians between 1 October 1997 and 30 September 1998. The life-table technique was used to calculate the number of susceptible children. On this basis, we estimated the corrected age-specific and cumulative incidence. RESULTS: We identified 1749 cases among the estimated 21,783 susceptible children, for a crude incidence of 8.0% (95% confidence interval [CI] = 7.7-8.4). The rate age-standardized to the Italian population 0-14 years old was 6.8 (CI = 6.5-7.2). The incidence was more than 16% among children age 3-4 years and more than 4% for those age 1-10 years. Comparison of the usual method and our corrected method showed that the uncorrected method underestimates the crude annual incidence (5.2% 8.0%), shifts the peak incidence to earlier ages, and underestimates cumulative incidence (at age 14, 49% 67%). CONCLUSIONS: The use of our corrected method provides more valid estimates of the incidence of varicella than the ones that are currently available. Corrected estimates should be preferred to uncorrected ones in models to study the cost-effectiveness of universal vaccination against varicella.     

A short-scheme protocol of gemeprost for midtrimester termination of pregnancy with uterine scar

OBJECTIVE: The purpose of this study is to investigate the safety and effectiveness of a short-scheme protocol of gemeprost for second trimester induction of abortion in women with previous uterine surgery. STUDY DESIGN: Retrospective review of women who underwent second trimester medical termination of pregnancy (TOP) at our hospital in a 5-year period. A short regimen of gemeprost was used: over a 24-h period, 1 mg vaginal gemeprost was given every 3 h up to three doses after which, if abortion did not occur, another course at the same dosage schedule was administered up to 4 days. Induction failure was defined as women undelivered by 96 h. A homogeneous population was identified. Statistical analysis was performed with the chi(2) test or Fisher's Exact Test for categorical data and t test for continuous variables. RESULTS: Four hundred seventeen women underwent medical midtrimester TOP in the 5-year study period. Two hundred five patients were selected for this review, comparing 63 patients with scarred uterus to 142 women without uterine scars. There were no differences between the two groups in induction-to-abortion interval and number of pessaries given. The overall failure of induction rate was 1.5% and need for blood transfusion was 0.5%. No uterine rupture was reported. CONCLUSION: The regimen of gemeprost proposed seems to be as safe and effective in patients with uterine scars as in women with unscarred uteri with a very low incidence of complications.     

Total antioxidant capacity of the diet is inversely and independently related to plasma concentration of high-sensitivity C-reactive protein in adult Italian subjects

Inflammation, a risk factor for cardiovascular disease, is associated with low plasma levels of antioxidant vitamins. In addition to vitamins, other antioxidants modulate the synthesis of inflammatory markers in vitro and contribute to the total antioxidant capacity (TAC) of a diet. However, the relationship between dietary TAC and markers of inflammation has never been evaluated in vivo. We investigated the relationship between dietary TAC and markers of systemic (high-sensitivity C-reactive protein (hs-CRP), leucocytes) and vascular (soluble intercellular cell adhesion molecule-1) inflammation in 243 non-diabetic subjects. General Linear Model (GLM) analysis showed a significant (P=0.005) inverse relationship between hs-CRP and quartiles of energy-adjusted dietary TAC, even when recognized modulating factors of inflammation, namely alcohol, fibre, vitamin C, alpha-tocopherol, beta-carotene, BMI, waist circumference, HDL-cholesterol, hypertension, insulin sensitivity and plasma beta-carotene, were included in the model as covariates (P=0.004). The relationship was stronger for subjects with hypertension (P=0.013 v. P=0.109 for normotensive individuals). Among dietary factors, TAC was significantly higher (5.3 (sd 3.0) v. 4.9 (sd 2.7) mmol Trolox/d; P=0.026) in subjects with low plasma hs-CRP (range: 0.0-4.1 mg/l) than in subjects with high plasma hs-CRP (range: 4.2-27.8 mg/l). We conclude that dietary TAC is inversely and independently correlated with plasma concentrations of hs-CRP and this could be one of the mechanisms explaining the protective effects against CVD of antioxidant-rich foods such as fruits, whole cereals and red wine. This could be of particular significance for subjects with high blood pressure.