Biphasic effect of l-5-HTP in the Vogel conflict model

The effect of l-5-HTP (25–400 mg/kg IP) following inhibition of the peripheral aromatic amino acid decarboxylase by means of benserazide (25 mg/kg IP) was investigated in a test modified from Vogel's drinking conflict model. At 50 mg/kg an anti-conflict action was detected, while higher doses (100–400 mg/kg) decreased punished responding. A lower dose (25 mg/kg) had no effect. Non-specific effects — such as alterations in muscle tone, in motivation to drink or in the sensitivity to electrical shock — could not explain the anxiolytic- and anxiogenic-like actions of 50 and 100 mg/kg, respectively. The bi-phasic effect of l-5-HTP is discussed in terms of different subpopulations of central serotoninergic receptors, possibly exerting opposing influences on conflict responding. The study emphasises the importance of 5-HT mechanisms in anxiety, and the possibility of finding novel anxiolytics among drugs selectively affecting central 5-HT neurotransmission.     

Treatment of cannabis use disorders in people with schizophrenia spectrum disorders — A systematic review

BackgroundCannabis use disorders (CUD) are prevalent among people with schizophrenia spectrum disorders (SSD), with a range of detrimental effects, e.g. reduced compliance to medication and psychosocial interventions, and increased level of psychotic-dimension symptoms. The aim of this study was to review literature on treatments of CUD in SSD-patients.MethodsPubMed, PsycINFO, EMBASE, and The Cochrane Central Register of Controlled Trials were searched.Results41 articles were selected, 11 treating cannabis as a separate outcome. Contingency management was only effective while active. Pharmacological interventions appeared effective, but lacked randomized controlled trials (RCTs). Psychosocial interventions, e.g. motivational interviewing and cognitive behavior therapy (CBT), were ineffective in most studies with cannabis as a separate outcome, but effective in studies that grouped cannabis together with other substance use disorders.ConclusionsInsufficient evidence exists on treating this form of dual-diagnosis patients. Studies grouping several types of substances as a single outcome may overlook differential effects. Future RCTs should investigate combinations of psychosocial, pharmacological, and contingency management.     

Application of brain microdialysis to study the pharmacology of the 5-HT1A autoreceptor

5-Hydroxytryptamine (5-HT) receptors of the 5-HT1A subtype are localized on serotoninergic cells and dendrites in the raphe nuclei of the brain stem and are believed to regulate synaptic 5-HT release through an inhibitory influence on serotoninergic impulse flow. The effects of 5-HT1A agonists on 5-HT release can, therefore, only be detected by measurement of 5-HT release from intact serotoninergic neurones. Here we review the evidence that the microdialysis technique, when applied to the anaesthetized rat, is able to detect extracellular 5-HT in the brain which derives from serotoninergic neurones and changes in accordance with serotoninergic neuronal activity. We have observed that a range of 5-HT1A agonists, including 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), inhibit 5-HT release in hippocampus, most probably by acting on somatodendritic 5-HT1A autoreceptors in the dorsal raphe nucleus. The inhibitory action of 8-OH-DPAT and several other selective 5-HT1A receptor active drugs on 5-HT release is sensitive to pindolol, further supporting the idea that the 5-HT receptor being measured is of the 5-HT1 subtype. Two drugs, BMY 7378 and NAN-190, which show 5-HT1A antagonist properties in certain models, reduce 5-HT release indicating that they have mixed agonist/antagonist actions at the 5-HT1A receptor. Our data indicate that measurement of 5-HT release in rat brain using the microdialysis technique may be a useful method to probe the pharmacology of the 5-HT1A autoreceptor in vivo.     

Age-related reference limits for urine levels of albumin, orosomucoid, immunoglobulin G and protein HC in children

Urine levels of albumin, orosomucoid (alias alpha1-acid glycoprotein), immunoglobulin G (IgG) and protein HC (alias alpha1-microglobulin) were determined in 247 healthy Swedish infants and children aged 1 day to 15 years. Urine samples were collected and stored in conditions known to guarantee stable protein levels. The protein levels were measured both as mass concentrations (mg l(-1)) and as protein-creatinine ratios (mg mmol(-1)). In an effort to arrive at practically useful upper reference limits, the variability with age for both units was analysed. The variability with age for the levels of three of the four proteins was considerably lower when the levels were expressed as creatinine ratios rather than as mass concentrations. The results allowed suggestion of the following upper reference limits, expressed as mg mmol(-1) creatinine, for use in clinical practise: IgG, 1 month to 15 years: 1.0; protein HC, 1 month to 15 years: 0.8; orosomucoid, 1 month to 15 years: 0.5; albumin, 1 month to 1 year: 3.8; 1-5 years: 3.3; 6-10 years: 2.7; 11-15 years: 2.1. In the immediate neonatal period the urine levels of all proteins were high and very variable.     

Determination of thyroid volume by ultrasonic scanning

A method for thyroid volume calculation based upon ultrasonic scanning is described. The accuracy of the method was estimated by comparing ultrasonically determined volumes with the volumes of surgically removed thyroid glands. The precision (i.e., reproducibility) was estimated by comparing the ultrasonic volumes determined by two separate investigators in a double blind fashion. The normal range of thyroid volume was evaluated in a group of volunteers. The accuracy was acceptable, but the precision was borderline and appears to be the limiting factor in the procedure. We concluded that at present this method offers no significant improvement over other methods currently in use. However, thyroid volume calculation based upon palpation of the gland cannot be standardized, and isotope scanning is a more comprehensive and expensive procedure. Several possibilities exist for improvement of the ultrasonic technique, and the procedure holds promise for the future.     

A mouse model for studying the interaction of bisdioxopiperazines with topoisomerase IIalpha in vivo

The bisdioxopiperazines such as (+)-(S)-4,4'-propylenedi-2,6-piperazinedione (dexrazoxane; ICRF-187), 1,2-bis(3,5-dioxopiperazin-1-yl)ethane (ICRF-154), and 4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione (ICRF-193) are agents that inhibit eukaryotic topoisomerase II, whereas their ring-opened hydrolysis products are strong iron chelator. The clinically approved analog ICRF-187 is a pharmacological modulator of topoisomerase II poisons such as etoposide in preclinical animal models. ICRF-187 is also used to protect against anthracycline-induced cardiomyopathy and has recently been approved as an antidote for alleviating tissue damage and necrosis after accidental anthracycline extravasation. This dual modality of bisdioxopiperazines, including ICRF-187, raises the question of whether their pharmacological in vivo effects are mediated through interaction with topoisomerase II or via their intracellular iron chelating activity. In an attempt to distinguish between these possibilities, we here present a transgenic mouse model aimed at identifying the contribution of topoisomerase IIalpha to the effects of bisdioxopiperazines. A tyrosine 165 to serine mutation (Y165S) in topoisomerase IIalpha, demonstrated previously to render the human ortholog of this enzyme highly resistant toward bisdioxopiperazines, was introduced at the TOP2A locus in mouse embryonic stem cells by targeted homologous recombination. These cells were used for the generation of transgenic TOP2A(Y165S/+) mice, which were demonstrated to be resistant toward the general toxicity of both ICRF-187 and ICRF-193. Hematological measurements indicate that this is most likely caused by a decreased ability of these agents to induce myelosuppression in TOP2A(Y165S/+) mice, highlighting the role of topoisomerase IIalpha in this process. The biological and pharmacological implications of these findings are discussed, and areas for further investigations are proposed.     

Lauryl ether sulphate dermatitis in Denmark

Lauryl ether sulphate (LES), a synthetic detergent, may sometimes contain an allergenic impurity, which has given rise to several outbreaks of contact dermatitis. Such an outbreak occurred in Denmark in 1971. All cases diagnosed were confined to one household, while other cases may have passed unnoticed.     

Occupational contact dermatitis from Cichorium (chicory, endive) and Lactuca (lettuce)

In two cases, occupational contact dermatitis was found to be due to chicory (Cichorium) used as a salad plant. In one of the two cases, contact sensitivity to letuce (Lactuca) was also observed. The sesquiterpene lactones of the plant may be the allergens.