Depressive symptoms and suicidal ideation during isotretinoin treatment: a 12-week follow-up study of male Finnish military conscripts.

OBJECTIVE: To investigate the putative association between isotretinoin treatment and depressive symptoms or suicidal ideation among Finnish male military conscripts. METHODS; Consecutive acne patients were enrolled into an uncontrolled, prospective 12-week follow-up study conducted at the Central Military Hospital, Helsinki, Finland. Of the 135 patients prescribed isotretinoin, 126 (93.3%) completed the follow-up. Depression and suicidal ideation were investigated with the Beck Depression Inventory (BDI) at baseline, weeks 4-6, and weeks 10-12. RESULTS: BDI mean score was low at baseline and declined further significantly (p < 0.001) during the follow-up from 3.0 (SD 3.948) to 1.8 (SD 3.783) among patients on isotretinoin. Moreover, the proportion of patients with clinically significant depressive symptoms (BDI > or= 10) declined non-significantly from 7.1 % to 3.2 %. Suicidal ideation was reported by 17 (13.5 %) patients at baseline and 9 (7.1%) patients at the end of the follow-up (NS). During the follow-up, one non-depressed patient attempted suicide while intoxicated by alcohol. CONCLUSION: On group level, isotretinoin seems not to be typically associated with treatment-emergent depression or suicidal ideation among young men. However, the possibility that individual patients may be susceptible for mood effects of isotretinoin as a rare idiosyncratic reaction can not be excluded.

Depressive symptoms, suicidal ideation and acne: a study of male Finnish conscripts.

OBJECTIVE: To investigate the association among acne, depressive symptoms and suicidal ideation in Finnish male military conscripts. METHODS: Consecutive 165 acne patients and 150 patients with mild knee symptoms for comparison were enrolled in the study conducted in the Central Military Hospital, Helsinki, Finland. They filled out the following questionnaires: General Health Questionnaire (GHQ-12), Beck Depression Inventory (BDI), Alcohol Use Disorders Identification Test and Rosenberg Self-Esteem Scale. The Leeds acne grading scale was used to estimate the severity of acne. RESULTS: Sixteen (9.7%) acne patients and 20 (13.3%) comparison patients had at least moderate level of depressive symptoms (BDI score 10; P > 0.05, between groups). Suicidal ideation (BDI suicidal item score 1) was reported by 24 (14.5%) acne patients and 16 (10.7%) comparison patients (P > 0.05, between groups). When comparing the mild facial acne patients (Leeds score 0-3) with those with moderate-severe facial acne (Leeds score 4), there were no statistical differences in depressive symptoms (9.5% vs. 10.0%) or suicidal ideation (13.7% vs. 15.7%). No linear relationship was observed between the BDI and facial Leeds scores (P > 0.05). Risk factors for suicidal ideation among the acne patients were depression and alcohol risk use. CONCLUSION: Young male patients with acne do not suffer more depressive symptoms or suicidal ideation than patients with mild knee symptoms, and the severity of acne is not associated with the presence of depressive symptoms. The risk factors for suicidal ideation among acne patients seem to be similar to those found in the general population.

Consumption of black currants, lingonberries and bilberries increases serum quercetin concentrations.

OBJECTIVE: To study serum quercetin concentrations of subjects consuming berries or habitual Finnish diets. DESIGN: Randomized parallel dietary intervention. SUBJECTS: Forty healthy men (age 60 y). INTERVENTION: Twenty subjects consumed 100 g/day of berries (black currants, lingonberries and bilberries) for 8 weeks. Twenty subjects consuming their habitual diets served as controls. Fasting blood samples were obtained 2 weeks prior to the study, at baseline, and at 2, 4 and 8 weeks. Intake of quercetin was assessed from 3 day food records collected at baseline and at 8 weeks. RESULTS: The serum quercetin concentrations were significantly higher in the subjects consuming berries compared to the control group (P=0.039 ANCOVA with repeated measures). During the berry consumption period the mean serum concentrations of quercetin ranged between 21.4 and 25.3 micro g/l in the berry group, which was 32-51% higher compared with the control group. According to 3 day food records, there was no difference in quercetin intake at baseline, but at 8 weeks the intake was 12.3+/-1.4 mg/day (mean+/-s.e.m.) in the berry group and 5.8+/-0.6 mg/day in the control group (P=0.001). CONCLUSIONS: The results indicate that the berries used in this study are a good source of bioavailable quercetin.

Detection and assay of cis- and trans-isomers of 4-methylaminorex in urine, plasma and tissue samples.

The 4-methylaminorex (4-MAX) is an amphetamine-related psychostimulant drug that has appeared on the clandestine market with a street name of "U4Euh". This compound exists as four stereoisomers, trans-4R,5R, trans-4S,5S, cis-4R,5S and cis-4S,5R, of which the cis forms have been classified as Schedule I substances in the US. The increasing variety of designer drugs has highlighted the importance of detection, identification, and quantitative measurement of these drugs, including 4-MAX, in biological samples. In the present study, the isomers of 4-MAX were detected in urine of rats treated with the drugs by some but not all of the on-site immunoassays tested, mainly as amphetamine or methamphetamine. To facilitate identification of 4-MAX by laboratories specialized in drug analysis, the electron-ionization mass spectrum and TLC data for underivatized 4-MAX using a routine laboratory drug-screening procedure is provided. In addition, a GC/MS method is described for the quantitative determination of cis- and trans-4-MAX as tert-butyldimethylsilyl-derivatives in plasma, urine and tissue.

Rewarding properties of methylphenidate: sensitization by prior exposure to the drug and effects of dopamine D1- and D2-receptor antagonists.

In drug addiction, a sensitization phenomenon has been postulated to play a critical role. The aim of our study was to evaluate whether sensitization occurs to the rewarding properties of methylphenidate, a psychostimulant drug known to possess abuse potential, as assessed with the biased conditioned place preference method in rats. In addition, since the brain dopaminergic system is considered to be important in drug-reward, the involvement of dopamine D1- and D2-receptors both in the rewarding properties of methylphenidate and in sensitization to these properties was assessed. Conditioning with methylphenidate at doses of 1.25 to 20 mg/kg increased preference for the paired environment, whereas a dose of 0.31 mg/kg was ineffective. However, following the 7-day sensitization treatment with methylphenidate (0.62-20 mg/kg), conditioning with a dose of 0.31 mg/kg resulted in an increased preference for the paired environment, i.e., the rewarding properties of methylphenidate appeared to be sensitized. Control experiments indicated that the enhancement of preference was not due to attenuation of sensitization treatment-induced withdrawal nor to tolerance to aversive properties of methylphenidate. When conditioned with methylphenidate, D1-antagonist SCH 23390 but not D2-antagonist raclopride prevented place preference. However, when coadministered with methylphenidate during the sensitization treatment, both SCH 23390 and raclopride prevented the development of sensitization. These data indicate that the rewarding properties of methylphenidate are sensitized by prior exposure to the drug and that both D1- and D2-receptors, the latter of which possibly more specifically, appear to be involved in the development of this sensitization.

Oxalic acid stabilizes dopamine, serotonin, and their metabolites in automated liquid chromatography with electrochemical detection.

Use of antioxidative agents is required in automated LC assay of microdialysis samples, due to rapid degradation of the monoamine neurotransmitters and their metabolites. Addition of oxalic acid prevented degradation of dopamine, serotonin, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid efficiently: after a 24-h incubation at room temperature the decreases in peak heights were less than 10%. The long-term stability of the analytes, however, was still enhanced when acetic acid and L-cysteine were included in the solution. Using this antioxidative solution, the monoamine neurotransmitters and their metabolites could be determined with an automated LC assay even at room temperature.

Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice.

The flavanones naringenin and hesperetin exhibit estrogenic, anticarcinogenic and antioxidative properties. Orange juice and grapefruit juice contain high amounts of these compounds, and therefore their intake from the diet can be relatively high. No data are available regarding plasma concentrations or plasma kinetics of flavanones. The objectives of this study were to develop methods allowing the analysis of naringenin and hesperetin from plasma and urine and to study their plasma kinetics and urinary excretion. We also wanted to assess whether plasma or urine flavanone concentrations can be used as biomarkers of intake. Healthy volunteers ingested orange juice (five women and three men) or grapefruit juice (two women and three men) once (8 mL/kg). Eleven blood samples and urine were collected between 0 and 24 h after juice administration. Flavanones were analyzed by HPLC with electrochemical detection. Naringenin and hesperetin were bioavailable from the studied juices, but interindividual variation in bioavailability was remarkable. The resulting plasma concentrations were comparatively high, and the peak plasma concentrations (C(max)) were 0.6 +/- 0.4 micromol/L (means +/- SD) for naringenin from orange juice and 6.0 +/- 5.4 micromol/L for naringenin from grapefruit juice. The corresponding value for hesperetin from orange juice was 2.2 +/- 1.6 micromol/L. The elimination half-lives were between 1.3 and 2.2 h, and therefore plasma concentrations reflect short-term intake. The relative urinary excretion varied depending on the flavanone source and dose and was 30.2 +/- 25.5% and 1.1 +/- 0.8% for naringenin from grapefruit juice and orange juice, respectively, and 5.3 +/- 3.1% for hesperetin from orange juice. The considerable difference in the relative urinary excretion of naringenin from the two juices was most likely caused by dose-dependent renal clearance rather than differences in bioavailability (as indicated by the similar C(max)-to-dose ratios). The results indicate that urine flavanone concentrations are not good biomarkers of dietary intake. We conclude that because of the relatively high concentrations of flavanones in plasma after ingestion of orange juice or grapefruit juice, considerable health effects could ensue in individuals consuming them regularly.

The effects of quinine and 4-aminopyridine on conditioned place preference and changes in motor activity induced by morphine in rats.

1. The effects of two unselective potassium (K(+)-) channel blockers, quinine (12.5, 25 and 50 mg/kg) and 4-aminopyridine (1 and 2 mg/kg), on conditioned place preference and biphasic changes in motor activity induced by morphine (10 mg/kg) were tested in Wistar rats. Quinine is known to block voltage-, calcium- and ATP-sensitive K(+)-channels while 4-aminopyridine is known to block voltage-sensitive K(+)-channels. 2. In the counterbalanced method, quinine attenuated morphine-induced place preference, whereas 4-aminopyridine was ineffective. In the motor activity test measured with an Animex-activity meter neither of the K(+)-channel blockers affected morphine-induced hypoactivity, but both K(+)-channel blockers prevented morphine-induced secondary hyperactivity. 3. These results suggest the involvement of quinine-sensitive but not 4-aminopyridine-sensitive K(+)-channels in morphine reward. It is also suggested that the blockade of K(+)-channels sensitive to these blockers is not sufficient to prevent morphine-induced hypoactivity whereas morphine-induced hyperactivity seems to be connected to both quinine- and 4-aminopyridine-sensitive K(+)-channels.

The effects of diazepam and zolpidem on cocaine- and amphetamine-induced place preference.

Drugs such as benzodiazepines, which enhance the effects of inhibitory neurotransmitter gamma-amino butyric acid (GABA), are known to modulate the mesocorticolimbic dopaminergic system, which is considered to mediate the rewarding effects of psychostimulants. The effects of diazepam, a benzodiazepine that binds unspecifically to omega 1- (omega1-) and omega2-receptors, and zolpidem, a nonbenzodiazepine drug that binds preferentially to omega1-receptors, on cocaine- and amphetamine-induced place preference were evaluated in Wistar rats. In tests using the counterbalanced method, neither diazepam (0.2, 1, and 5 mg/kg) nor zolpidem (2.5, 5, and 10 mg/kg) alone induced place preference or place aversion. Diazepam pretreatment prevented both cocaine- and amphetamine-induced (15 and 9 mg/kg, respectively) place preference; however, at doses that were earlier shown to cause sedation and amnesia, zolpidem failed to prevent either cocaine- or amphetamine-induced place preference. These results suggest that diazepam interferes with the rewarding properties of the psychostimulants, whereas zolpidem is less effective in this respect, possibly due to differential distribution of omega1- and omega2-receptors in the brain.

Creatine and caffeine in anaerobic and aerobic exercise: effects on physical performance and pharmacokinetic considerations.

The pharmacokinetics and effects of creatine and caffeine administration on anaerobic and aerobic performance of 7 trained athletes were studied in a randomized, placebo-controlled, double-blind crossover design. The treatments were: placebo (PLA), a single oral dose (7 mg x kg(-1)) of caffeine (CAF), repeated oral doses (3 x 100 mg x kg(-1) x day(-1)) of creatine for 3 days (CRE), or the combination of caffeine and creatine (CAF + CRE) before physical exercise. In one session CAF was administered without exercise. Drug administration was followed by 3 repetitive 1-minute exercise bouts on a bicycle ergometer at maximal speed (anaerobic exercise) starting 70 min after drug administration. Anaerobic exercise was followed by 45 min of cycling at constant pedalling speed and workload (aerobic exercise). CRE and CAF, alone or in combination, did not improve maximal pedalling speed (rpm), maintenance of maximal speed (rpm) or total work output (kJ) during the 1 -minute bouts, when compared with PLA. In addition, no statistically significant differences in heart rate or blood lactate were observed between the treatments either during anaerobic or aerobic exercise bouts. Creatine was rapidly and efficiently absorbed, as reflected by plasma concentrations. The mean +/-SEM value for creatine Cmax was 1.22+/-0.14 mmol x l(-1), tmax 92+/-7 min and plasma half-life (t1/2beta) 172+/-21 min. Caffeine pharmacokinetics were not affected by concomitant administration of creatine or by physical exercise. In conclusion, neither maximal performance and subsequent recovery nor aerobic performance were enhanced by oral creatine supplementation in the study.

The acute effects of amphetamine derivatives on extracellular serotonin and dopamine levels in rat nucleus accumbens.

The acute effects of amphetamine derivatives on extracellular concentration of serotonin (5-HT) and dopamine in the nucleus accumbens were studied with in vivo microdialysis using conscious, freely moving rats. 5-HT, dopamine, and their major metabolites were measured by HPLC with electrochemical detection. Amphetamine (1.0-9.0 mg/kg) elevated dopamine levels considerably, but failed to affect the levels of 5-HT, except at the highest dose administered. 3,4-Methylenedioxyamphetamine (MDA, 1.0-9.0 mg/kg) and 3,4-methylenedioxymethamphetamine (MDMA, 1.0-9.0 mg/kg) elevated both 5-HT and dopamine levels dose dependently. The failure of 2,5-dimethoxy-4-methylamphetamine (DOM, 0.5-1.0 mg/kg) to affect the 5-HT levels suggests that extracellular levels of 5-HT play a minor role in hallucinogenic activity. The strong effects of MDA and MDMA on levels of 5-HT indicate that their actions on serotonergic mechanisms are different from those of the hallucinogens. In addition, methylenedioxyamphetamines may act via dopaminergic mechanisms similar to those of amphetamine.