The effect of zinc on 9, 10 dimethyl- 1, 2 benzanthracene(DMBA) induced salivary gland tumours in the albino rat. A preliminary study

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Effect of Valproate and Antidepressant Drugs on Clozapine Metabolism in Patients With Psychotic Mood Disorders

BACKGROUND: The aim of the present study was to appraise retrospectively the influence of valproate (VPA) and antidepressants (ADs) on the steady-state plasma concentrations of clozapine (CLZ), the prototype of various second-generation antipsychotics, norclozapine (NCLZ, its main metabolite), and their ratio (NCLZ:CLZ). METHODS: Sixty-seven psychotic patients with a prevalent diagnosis of bipolar disorder were studied. We then analyzed data altogether and subdivided them into 4 groups, according to pharmacological treatments: #1 CLZ (n = 21), #2 CLZ plus ADs (n = 13), #3 CLZ plus VPA (n = 16), and #4 CLZ plus ADs plus VPA (n = 17). RESULTS: First, significant positive between CLZ and NCLZ plasma levels (in nanograms/milliliter) and the drug daily dosages (in milligrams/kilogram of body weight) (n = 67) were observed (Spearman: rCLZ = 0.49; rNCLZ = 0.61; P < 0.001). We then normalized by given doses CLZ and NCLZ plasma levels, natural log transformed them, and performed analysis of variance factor analyses followed by pairwise comparisons, performed on the 4 groups and the 3 CLZ parameters. We identified significant drug effects on (1) CLZ plasma levels, significantly higher in group #2 versus group #1, and (2) NCLZ:CLZ ratio, lower in group #2 versus groups #1 and #3. Significant drug × gender interactions were observed in group #3, showing higher NCLZ levels and NCLZ:CLZ ratios in men compared with women. CONCLUSIONS: Despite its inherent limitations, this observational study confirms the significant increase in plasma CLZ concentrations and reduction in NCLZ:CLZ ratio when this drug was coadministered with ADs (group #2), an effect apparently counteracted by VPA (group #4). The drug × gender interactions in patients taking both CLZ and VPA (group #3) warrant further prospective study

Significance of REM sleep dysregulation in depression: State of the art (In press.)

Disturbances of sleep are typical for most depressed patients and belong to the core symptoms of the disorder. Since the 1960ies polysomnographic sleep research has demonstrated that besides disturbances of sleep continuity, depression is associated with altered sleep architecture, i.e. a decrease in slow wave sleep (SWS) production and disturbed REM sleep regulation. Shortened REM latency (i.e. the interval between sleep onset and the occurrence of the first REM period), increased REM sleep duration and increased REM density (i.e. the frequency of rapid eye movements per REM period) have been considered as biological markers of depression which might predict relapse and recurrence. High risk studies including healthy relatives of patients with depression demonstrate that REM sleep alterations may precede the clinical expression of depression and may thus be useful in identifying subjects at high risk for the illness. Several models have been developed to explain REM sleep abnormalities in depression, like the cholinergic-aminergic imbalance model or chronobiologically inspired theories, which are reviewed in this overview. Moreover, REM sleep alterations have been recently considered not only as biological "scars" but as true endophenotypes of depression. This review discusses the genetic, neurochemical and neurobiological factors that have been implicated to play a role in the complex relationships between REM sleep and depression. We hypothesize on the one hand that REM sleep dysregulation in depression may be linked to a genetic predisposition/vulnerability to develop the illness; on the other hand it is conceivable that REM sleep disinhibition in itself is a part of a maladaptive stress reaction with increased allostatic load. We also discuss whether the REM sleep changes in depression may contribute themselves to the development of central symptoms of depression such as cognitive distortions including negative self-esteem and the overnight consolidation of negatively toned emotional memories

REM sleep dysregulation in Depression: State of the Art

Disturbances of sleep are typical for most depressed patients and belong to the core symptoms of the disorder. Since the 1960s polysomnographic sleep research has demonstrated that besides disturbances of sleep continuity, depression is associated with altered sleep architecture, i.e., a decrease in slow wave sleep (SWS) production and disturbed rapid eye movement (REM) sleep regulation. Shortened REM latency (i.e., the interval between sleep onset and the occurrence of the ␣rst REM period), increased REM sleep duration and increased REM density (i.e., the frequency of rapid eye movements per REM period) have been considered as biological markers of depression which might predict relapse and recurrence. High risk studies including healthy relatives of patients with depression demonstrate that REM sleep alterations may precede the clinical expression of depression and may thus be useful in identifying subjects at high risk for the illness. Several models have been developed to explain REM sleep abnor- malities in depression, like the cholinergiceaminergic imbalance model or chronobiologically inspired theories, which are reviewed in this overview. Moreover, REM sleep alterations have been recently considered not only as biological “scars” but as true endophenotypes of depression. This review discusses the genetic, neurochemical and neurobiological factors that have been implicated to play a role in the complex relationships between REM sleep and depression. We hypothesize on the one hand that REM sleep dysregulation in depression may be linked to a genetic predisposition/vulnerability to develop the illness; on the other hand it is conceivable that REM sleep disinhibition in itself is a part of a maladaptive stress reaction with increased allostatic load. We also discuss whether the REM sleep changes in depression may contribute themselves to the development of central symptoms of depression such as cognitive distortions including negative self-esteem and the overnight consolidation of negatively toned emotional memories

REM sleep dysregulation in depression: State of the art

Disturbances of sleep are typical for most depressed patients and belong to the core symptoms of the disorder. Since the 1960s polysomnographic sleep research has demonstrated that besides disturbances of sleep continuity, depression is associated with altered sleep architecture, i.e., a decrease in slow wave sleep (SWS) production and disturbed rapid eye movement (REM) sleep regulation. Shortened REM latency (i.e., the interval between sleep onset and the occurrence of the first REM period), increased REM sleep duration and increased REM density (i.e., the frequency of rapid eye movements per REM period) have been considered as biological markers of depression which might predict relapse and recurrence. High risk studies including healthy relatives of patients with depression demonstrate that REM sleep alterations may precede the clinical expression of depression and may thus be useful in identifying subjects at high risk for the illness. Several models have been developed to explain REM sleep abnormalities in depression, like the cholinergic-aminergic imbalance model or chronobiologically inspired theories, which are reviewed in this overview. Moreover, REM sleep alterations have been recently considered not only as biological "scars" but as true endophenotypes of depression. This review discusses the genetic, neurochemical and neurobiological factors that have been implicated to play a role in the complex relationships between REM sleep and depression. We hypothesize on the one hand that REM sleep dysregulation in depression may be linked to a genetic predisposition/vulnerability to develop the illness; on the other hand it is conceivable that REM sleep disinhibition in itself is a part of a maladaptive stress reaction with increased allostatic load. We also discuss whether the REM sleep changes in depression may contribute themselves to the development of central symptoms of depression such as cognitive distortions including negative self-esteem and the overnight consolidation of negatively toned emotional memories. © 2012 Elsevier Ltd