De Luca RD, Fraga DB, Ghedim FV, Kolling J, Ferreira AGK, Cunha AA, Wyse ATS, Zugno AI. Na+,K+-ATPase activity is increased in rats subjected to chronic administration of ketamine.

Objective: Schizophrenia is a devastating psychiatric disorder. Symptoms of schizophrenia can be divided into positive, negative and cognitive, and the physiopathology is still been unknown. Na+,K+-ATPase is a protein in its role as a maintainer of fluid balance in all mammals and alterations in this enzyme could cause brain abnormalities. The aim of our study was to investigate the activity of this enzyme in rats submitted to chronic administration of ketamine.

Methods: Adult male Wistar rats were submitted to sub-anaesthetic doses of the 25 mg/kg ketamine by seven consecutive days and the Na+,K+-ATPase activity was analysed in prefrontal and hippocampus of rats.

Results: We observed an increase in Na+,K+-ATPase activity in prefrontal cortex administration of 25 mg/kg ketamine. However, ketamine has no effect in hippocampus.

Conclusion: This evidence indicates that the alteration in Na+,K+-ATPase may be related with glutamatergic system and consequently could be related to the development of schizophrenia.

de Macedo-Soares MB, Brietzke E, da Silva Dias R, Mendonca T, Moreira C, Lafer B. A comparison of the symptomatic profile between two consecutive depressive episodes in patients with bipolar disorder type I.

Kitaichi Y, Inoue T, Nakagawa S, Boku S, Koyama T. Effects of combined treatment with clorgyline and selegiline on extracellular noradrenaline and serotonin levels.

Objective Combined treatment with clorgyline, an irreversible monoamine oxidase (MAO)-A inhibitor, and selegiline, an irreversible MAO-B inhibitor, reportedly increases extracellular serotonin levels in the raphe nuclei more than clorgyline does alone. However, the effects of combination of these MAO inhibitors on extracellular noradrenaline have not been reported.

Methods Using in vivo microdialysis, we measured extracellular noradrenaline and serotonin levels after administration of clorgyline and/or selegiline in the medial prefrontal cortex of rats.

Results Administration of clorgyline (10 mg/kg) significantly increased both extracellular serotonin and noradrenaline levels. Combined treatment using clorgyline (10 mg/kg) and selegiline (3 mg/kg) increased extracellular serotonin and noradrenaline levels more than each drug alone did.

Conclusions These findings of this study suggest the augmented antidepressant action of the combination of MAO-A inhibition and MAO-B inhibition. The addition of a MAO-A inhibitor to selegiline or increasing dose of selegiline to achieve full MAO-A inhibition might be the promising strategy for the antidepressant treatment in partial responders or non-responders to selegiline.

Immunopathogenesis of multiple sclerosis is a complex process involving T cell mediated autoimmunity at initial stage of disease. A long standing view that Th1 cells are critical for early inflammatory development of lesions is challenging by recent findings that Th1 helper cells with Th17 phenotype are even more important. A complex autoimmunity of MS is further complicated with evidence that CD8 cells, regulatory T cells, clonal expansion of B cells, cells of myelin lineage, antibodies and complement, as well as process intrinsic to central nervous system contribute to the tissue destruction. Although there are a lot of evidences about inflammatory phase of MS, far less is known about mechanisms involved in degenerative phase of disease. It is not known weather quantitative, or qualitative differences in inflammatory response contributes to destruction of the tissue, or as it was shown experimentally demyelination may sometimes occur independent of T cells.

Understanding of immunopathogenesis of MS especially regarding various stages of disease is necessary for clinicians in choosing optimal therapy of MS in individual patients. Influences of immunomodulatory treatment on various stages of MS immuno-pathogenesis are presented.

Heroin has been prescribed in England for the treatment of heroin addiction for almost 100 years. For many years, England was almost the only country where this occurred, and the British system was consequently the subject of international curiosity. In spite of this long history, very little research has been carried out locally, and until recently, there were no guidelines as to best practice. In 1965, it was decided that only doctors with a Home Office license could prescribe heroin. Since that time, the proportion of opiate addicts treated with heroin has greatly diminished, as has the number of doctors willing to prescribe. One doctor in particular remained an enthusiastic proponent of heroin prescription. His claims impressed some Swiss clinicians, who proceeded to establish a multicentre trial in Switzerland. This was followed by a similar trial in the Netherlands. These trials apparently indicated that a proportion of treatment-resistant opiate addicts could respond well to heroin, although the researchers' conclusions have been disputed. The National Treatment Agency in England is now developing guidelines for good practice based on this new information and is planning to set up some pilot sites. It is likely that practise in England will remain somewhat different from continental practice, particularly with respect to long-term supervised injecting. It is unclear how much funding will be released to support heroin prescription. Without adequate funding, it is likely to disappear.