Antidepressant drugs are widely used to treat mood and anxiety disorders. However, the cellular mechanisms underlying their therapeutic effects and adverse reactions are not well understood. We have shown that chronic treatment with the serotonergic antidepressant fluoxetine causes various changes in physiological functions of granule cells in the hippocampal dentate gyrus in mice. A lower dose of fluoxetine can stabilize serotonergic modulation at the synapse formed by the mossy fiber axon of the granule cell onto the pyramidal cell in the CA3 region. A higher dose of fluoxetine markedly enhances both serotonergic and dopaminergic modulations at the mossy fiber synapse. In addition, higher-dose fluoxetine reverses the state of maturation of the dentate granule cells in adult mice. After treatment with fluoxetine, the granule cell shows immature physiological properties, including higher somatic excitability and reduced frequency facilitation at the mossy fiber synapse. This "dematuration" is induced in a large population of the dentate neurons and is maintained for at least 1 month after withdrawal of fluoxetine. In a mouse model of neuroendocrine dysregulation of mood disorders produced through chronic treatment with corticosterone, the fluoxetine-induced plastic changes in the dentate gyrus are facilitated, and the granule cell dematuration can be induced at a fluoxetine dose producing blood levels comparable to those in patients receiving chronic fluoxetine treatment. Our findings suggest that the fluoxetine-induced plastic changes in the hippocampal dentate gyrus are candidate cellular bases involved in mechanisms of action of antidepressant drugs.

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Hydroxycarbamide, also known as hydroxyurea, is a nucleic-acid metabolic antagonist used to treat myeloproliferative disorders, such as chronic myelocytic leukemia, polycythemia vera, and essential thrombocythemia. We present an 85-year-old woman in whom skin ulcers developed on the posterior aspect of the calcaneal region bilaterally after she was treated with hydroxycarbamide for essential thrombocythemia. The ulcers were resistant to conventional therapy but healed 1 month after the discontinuation of hydroxyurea and the application of a steroid ointment. Clinicians should therefore be aware of this potential adverse effect of hydroxycarbamide.

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The main part of the statistics is an investigating of the population by using samples. In this issue we state about a normal population first. In statistics we assume that a population follows a normal distribution in most cases. It is rational practically and theoretically. Another subject is the idea and methods of estimation (point estimation and interval estimation). We understand that point estimation itself is seldom used in the medical scene. However, the maximum likelihood estimation that is considered under the claims in point estimations is used as a value in several statistical methods. In interval estimations we can discuss the accuracy also.

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