Clinical characteristics distinguishing tramadol-using adolescents from other substance-using adolescents in an out-patient treatment setting.

BACKGROUND: Non-medical Prescription Opioid Use (NMPOU) has increased worldwide during the last decades, and specifically, tramadol misuse may represent a novel pattern of substance use among adolescents. The present study aims to analyze characteristics distinguishing tramadol-using adolescents from other substance-using adolescents seeking out-patient treatment. METHODS: This is a cross-sectional study of treatment-seeking patients between 13 and 24 years of age in an out-patient facility for substance use problems in Malmö, Sweden. A total of 526 treatment-seeking adolescents at an out-patient treatment center were included. Data on substance use, treatment history and socio-demographic variables were extracted through a semi-structured interview method aimed specifically for adolescents with alcohol or drug problems (Ung-DOK). Lifetime tramadol users were compared to non-users, and also, primary tramadol users were compared to remaining subjects. RESULTS: Thirty-one percent (n = 162) were tramadol users (lifetime prevalence). In logistic regression, the tramadol group showed a significantly increased risk of tobacco use, problematic lifetime cocaine, benzodiazepine and amphetamine use, and were more likely to report contacts with the judicial system, and less likely to report contacts with child or adult psychiatry, and more likely to have parents born outside the Scandinavian countries. In logistic regression, primary tramadol use was negatively associated with frequent cannabis use. CONCLUSIONS: Tramadol use appears to be a novel pattern among treatment-seeking adolescents. They showed a significantly increased risk of initiation of other illicit drugs and criminal behaviour, despite less contact with psychiatric care. More attention may be needed to this relatively novel pattern of opioid use.

Analysis of rpsD mutations in Escherichia coli. II. Physiology of some representative mutants.

The effects of ribosomal ambiguity mutations (ram A-) on the assembly of ribosomal 30S subunits in Escherichia coli were studied in some representative mutant strains. It was found that the inability of these strains to produce active 30S subunits at nonpermissive temperatures is correlated with a halt in the accumulation of protein S4. It is demonstrated that 30S-precursor particles lacking this protein accumulate and break down at nonpermissive temperatures and that most of the 30S proteins as well as the 17S RNA constituting these particles are similarly unstable. These findings are discussed and related to the finding that merodiploid strains containing genes for both mutant and wild type protein S4 do not accumulate the mutant form of the protein. Experiments indicating that ribosomal precursor particles are associated with polysomes are presented. The implications of these findings are discussed and it is suggested that the assembly of ribosomes is tightly coupled to the synthesis of ribosomal proteins.

Analysis of rpsD mutations in Escherichia coli. I. Comparison of mutants with various alterations in ribosomal protein S4.

Streptomycin-independent revertants were selected from streptomycin-dependent mutants. Twenty-five out of 150 such revertants were temperature sensitive. Ribosomal proteins from 18 temperature-sensitive and 10 temperature-insensitive revertants were analysed by SDS-polyacrylamide gel electrophoresis. Seventeen of the former but none of the latter category showed an alteration of protein S4. The mutated rpsD allele of 6 temperature-sensitive revertants was transduced into a rpsL+ strain. In all cases an increased suppressibility of T4 amber phages was observed. Such suppressibility was not observed in the original rpsD, rpsL strains. All 18 temperature-sensitive mutants were disturbed in the processing of 17s to 16s RNA at non-permissive temperature and the accumulated 17s RNA was degraded. Temperature-insensitive rpsD revertants could be isolated, which had gained a second alteration in S4. Such revertants, which had lost the temperature-sensitive property, were also unable to suppress growth of T4 amber phages. It is concluded that temperature-sensitive growth, inability to process 17s RNA and to assemble 30S ribosomes at non-permissive temperature as well as increased translational ambiguity are highly correlated properties in rpsD mutants.

Analysis of rpsD mutations in Escherichia coli. III. Effects of rpsD mutations on expression of some ribosomal protein genes.

Relative rates of production and steady state levels of ribosomal proteins were determined in a temperature sensitive rpsD (S4) mutant of Escherichia coli. Some proteins (S4, S12, S13) were overproduced in the mutant at permissive temperature but steady state levels of all examined ribosomal proteins were normal. In a rpsD+/rpsD+ homodiploid strain the relative rates of production of ribosomal proteins were not affected by the increased gene dose. In a rpsD+/rpsD heterodiploid strain only wild type, but not mutant S4, was found. In such a strain S4, S7, S12 and probably S13 is overproduced. It is implied that S4 is involved in the regulation of expression of proximal genes of the two transcriptional units including the genes coding for S4 itself and S12, respectively. A degradation system for ribosomal proteins, which is rapid enough to be of regulatory significance, is demonstrated.

Post-transciptional control of coordinated ribosomal protein synthesis in Escherichia coli.

The synthesis of the approximately 50 different ribosomal proteins (r proteins) is very well coordinated in Escherichia coli. As the r-protein genes are arranged in many different operons, placed at separate locations on the E. coli chromosome, it is not obvious how this coordination is maintained. The first indication that special controls are involved in the coordination came from the observations that merodiploid strains containing F' factors with some of the ribosomal genes also synthesise the r proteins in balanced amounts. The overall regulation of r-protein synthesis in reponse to changes in growth conditions is primarily mediated by changes in the rate of transcription of the r-protein genes. To investigate whether the gene dosage control seen in merodiploid strains is also transcriptional in nature or whether other mechanisms are involved, we compared the transcriptionof r-protein mRNA in haploid and merodiploid strains. It was found that the rate of transcription of the r-protein mRNA from the str-spc cluster of genes changes in proportion to the gene dosage and it is concluded that the expression of r-protein genes is adjusted by post-transcriptional control.

Analysis of rpsD mutations in Escherichia coli. IV. Accumulation of minor forms of protein S7(K) in ribosomes of rpsD mutant strains due to translational read-through.

A certain proportion of protein S7 exists in an altered form in E. coli rpsD (S4) mutants. Depending on the type of S4 mutation involved, two different forms of the altered S7 can be distinguished. The unusual form is longer than normal S7 by about 500 daltons due to extra material at the carboxyl end of the protein. It is suggested that a mutationally altered S4 might lower the efficiency of termination during translation of the messenger for S7. This results in an increased frequency of translational read-through, which gives the observed longer forms of S7. Data are interpreted to mean that one class of S4 mutants might suppress UGA and UAG whereas another class only suppresses UGA.