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Alitretinoin given at well-tolerated doses induced clearing of CHE in a substantial proportion of patients with severe disease refractory to standard therapy.

The first druglike selective angiotensin II AT(2) receptor agonist (21) with a K(i) value of 0.4 nM for the AT(2) receptor and a K(i) > 10 microM for the AT(1) receptor is reported. Compound 21, with a bioavailability of 20-30% after oral administration and a half-life estimated to 4 h in rat, induces outgrowth of neurite cells, stimulates p42/p44(mapk), enhances in vivo duodenal alkaline secretion in Sprague-Dawley rats, and lowers the mean arterial blood pressure in anesthetized, spontaneously hypertensive rats. Thus, the peptidomimetic 21 exerts a similar biological response as the endogenous peptide angiotensin II after selective activation of the AT(2) receptor. Compound 21, derived from the prototype nonselective AT(1)/AT(2) receptor agonist L-162,313 will serve as a valuable research tool, enabling studies of the function of the AT(2) receptor in more detail.

BACKGROUND AND PURPOSEThe designer drug 1-(4-methylphenyl)-2-methylaminopropan-1-one (4-methylmethcathinone, mephedrone) is reported to possess psychostimulant, entactogenic and hallucinogenic effects. The purpose of this study was to examine the effects of acute administration of mephedrone on extracellular levels of dopamine (DA) and 5-HT in the nucleus accumbens of awake rats and compare these effects with those induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and amphetamine. EXPERIMENTAL APPROACHMicrodialysis sampling was performed while simultaneously recording locomotor activity in rats and the monoamines were determined by HPLC with electrochemical detection. KEY RESULTSMephedrone (3 mg·kg -1 s.c.) and (+)-amphetamine (1 mg·kg -1 s.c.) caused rapid increases in extracellular DA levels of 496% and 412%, respectively, whereas MDMA (3 mg·kg -1 s.c.) showed only a moderate effect (235%). The corresponding 5-HT levels increased to 941% (mephedrone) and 911% (MDMA), but only to 165% following amphetamine. The calculated t1/2 values for elimination rate of mephedrone, MDMA and amphetamine-induced increases in extracellular DA levels were 25, 303 and 51 min, the corresponding t1/2 values for 5-HT were 26, 48 and 84 min, respectively. Locomotor activity was increased most by amphetamine, whereas both mephedrone and MDMA showed about three times lower and shorter-lasting effects. CONCLUSIONS AND IMPLICATIONSThe neurochemical and functional properties of mephedrone resemble those of MDMA, but it also shows an amphetamine-like effect in that it evokes a rapid release and elimination of DA in the brain reward system, a feature that may contribute to its potent re-inforcing properties.

Objective. To compare the levels of biogenic mines in the cerebrospinal fluid (CSF) of primary fibromyalgia syndrome (PFS) patients with those in the CSF of controls.Methods. Metabolites of serotonin, norepinephrine, and dopamine were identified in CSF, using high performance liquid chromatography with coulometric detection.Results. CSF levels of metabolites from all 3 neurotransmitters were lower in PFS patients than in controls . Conclusion.A low rate of turnover of several neurotransmitters supports the proposed hypothesis of a metabolic defect in PFS and suggests that the defect occurs at a neuroregulatory level.Primary fibromyalgidfibrositis syndrome (PFS) is a chronic, painful musculoskeletal disorder com-

This is the first nationwide epidemiological study on CLE. We found the incidence of CLE to be about equal to that of SLE, and found a higher short-term probability for receiving an additional diagnosis with SLE than previously described for CLE. Subsets other than DLE and SCLE were rarely reported in our system; an update of the ICD codes for this diagnostic group could increase reporting of these more unusual cases. Our study clarifies that monitoring and follow-up are called for in this patient group due to the risk for SLE, and underscores the need for clear criteria for risk assessment in the large group of patients with CLE who also fulfil criteria for SLE.

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Use of doping agents probably involves more than a desire to enhance appearance or sports performance and appears to have much in common with use of alcohol, tobacco and psychotropic drugs.