Methodological aspects of follow-up studies on psychotic patients in a polydiagnostic perspective.

Polydiagnostic follow-up studies should explore whether certain definitions of a given disorder permit better prediction of the illness course than others and whether this good predictive validity is related to specific etiopathogenetic conditions. In order to carry out such studies successfully they should be based on broadly defined samples and comprise provisions for additional validation such as genetic data, neuropsychological testing etc. After an assessment at baseline and at discharge from hospital, the follow-up assessments should comprise five steps: (1) Identification of successful and unsuccessful diagnostic systems; (2) identification of features determining successful attribution; (3) analysis of successful systems; (4) analysis of unsuccessful systems, and (5) analysis of cases which have changed diagnostic attribution. The conclusions drawn from these analyses are intended to refine classification in psychiatry.     

Pharmacokinetic aspects of a combination of metoclopramide and paracetamol. Results of a human kinetic study and consequences for migraine patients]

An open trial was carried out in eight healthy male and female volunteers to examine the bioavailability as well as the main kinetic parameters of Migr?nerton (metoclopramide and paracetamol; CAS 364-64-5 and CAS 103-90-2, resp). in comparison with reliable literature data. The results reported here clearly show that the absorption of both active ingredients from the fixed combination is complete and that therapeutically relevant plasma concentrations are achieved within 30 min. Bioavailability as well as tmax, t1/2, and time-lag are comparable with data resulting from reliable and internationally acknowledged kinetic studies. The fixed combination was shown to be kinetically compatible with regard to all parameters determined for metoclopramide and paracetamol.     

Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate

We observed that pretreatment of male F344 rats with benzyl selenocyanate, a versatile organoselenium chemopreventive agent in several animal model systems, decreases the levels of DNA and RNA modifications produced in the liver by the hepatocarcinogen 2- nitropropane. To clarify the mechanisms involved, we pretreated male F344 rats with either benzyl selenocyanate, its sulfur analog benzyl thiocyanate, phenobarbital or cobalt protoporphyrin IX; the latter is a depletor of P450. We then determined (1) the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on 2-nitropropane- induced liver DNA and RNA modifications and (3) amount of nitrate excreted in rat urine following administration of the carcinogen. Pretreatment with benzyl selenocyanate or phenobarbital increased the denitrification activity of liver microsomes by 217 and 765%, respectively, increased liver P4502B1 by 31- and 435-fold, respectively, decreased the levels of 2-nitropropane-induced modifications in liver DNA (29-70% and 17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and increased the 24-h urinary excretion of nitrate by 157 and 209%, respectively. Pretreatment with benzyl thiocyanate had no significant effect on any of these parameters. Pretreatment with cobalt protoporphyrin IX decreased liver P4502B 1 by 87%, decreased the denitrification activity of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic acid modifications by 17-67%. These results indicate that the metabolic sequence from 2-nitropropane to the reactive species causing DNA and RNA modifications does not involve the removal of the nitro group. Moreover, they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic acid modifications in part by increasing its detoxication through induction of denitrification, although it is evident that other mechanisms must also be involved.