Antidepressant-induced switching is a major risk during the treatment of bipolar depression. Despite several clinical studies, questions remain regarding both the definition of these mood switches and the most appropriate therapeutic strategy to avoid this adverse effect.This review will first briefly consider the current guidelines for the acute treatment of bipolar depression. We will then review the mechanisms of action of antidepressant and mood stabilisers, and the switches induced by various types of antidepressant treatments, or triggered by antidepressant withdrawal, as well as by atypical antipsychotics. We then will address the risk of mood switch according to the type of mood stabiliser used. The propensity to mood switches in bipolar patients is subject to individual differences. Therefore we will describe both the clinical and biological characteristics of patients prone to mood switches under antidepressant treatment. However, the clinical characteristics of the depressive syndrome may also be a key determinant for mood switches. Various data help identify the most appropriate drug management strategies for avoiding mood switches during the treatment of bipolar depression. Selective serotonin reuptake inhibitors appear to be the drugs of first-choice because of the low associated risk of mood switching. Antidepressants must be associated with a mood stabiliser and the most effective in the prevention of switches seems to be lithium. Whatever the mood stabiliser used, effective plasma levels must be ensured. The optimal duration of antidepressant treatment for bipolar depression is still an open issue - prolonged treatments after recovery may be unnecessary and may facilitate mood elation. Moreover, some mood episodes with mixed symptoms can be worsened by antidepressants pointing to the need for a better delineation of the categories of symptoms requiring antidepressant treatment. Finally, as a result of this review, we suggest some propositions to define drug-induced switches in bipolar patients, and to try to delineate which strategies should be recommended in clinical practice to reduce as far as possible the risk of mood switch during the treatment of bipolar depression. 相似文献
Bath application of
-fucose and
-fucosyllactose (
F1 increases the potentiation of the population spike amplitude (POP-spike) and the field excitatory postsynaptic potential (fEPSP) after tetanization of the Schaffer collaterals of the rat hippocampus. The ineffective isomers
-fucose and 3-fucosyllactose (3-F1) have no such effect. Since not only the maintenance of long-term potentiation LTP is influenced but also its induction is drastically improved, an effect of the sugars via the formation of glycoproteins but also via different actions on induction mechanisms is discussed. 相似文献
Brain tissues from 6 patients with concentric sclerosis (Baló) were examined by in situ hybridization, immunocytochemistry, morphometry, and histological methods. The patients were 24 to 48 years old and had progressive cerebral symptoms and signs that lasted 15 to 100 days. Large demyelinative lesions, most frequent in the frontal white matter, contained alternating bands of demyelinated and partly myelinated white matter that were arranged in concentric or mosaic patterns. In the areas of demyelination, axons were relatively well preserved and there were perivascular inflammatory infiltrates. In 2 specimens, lesions contained regions with the characteristic appearance of actively demyelinating multiple sclerosis plaques. Oligodendroglial densities were highest in normal-appearing white matter, lower in partially myelinated areas, and lowest in demyelinated areas, which also contained many hypertrophic astrocytes closely associated with oligodendroglia. Messenger RNA levels for myelin-related proteins followed the same pattern; they were lowest in demyelinated areas, higher in partially myelinated areas, and highest in normal-appearing white matter beyond lesion margins. Our findings suggest that concentric sclerosis is a variant of multiple sclerosis, that oligodendroglial loss is important in the pathogenesis of demyelination, and that partially myelinated areas probably represent stages of ongoing myelin breakdown rather than remyelination of previously demyelinated areas. 相似文献
Mixing pharmaceutical preparations of soluble neutral regular insulin solution (NRI) and neutral protamine Hagedorn (NPH) crystalline insulin suspension leads to a reduction in the measurable amount of soluble insulin in the formulation supernatant. However in spite of the loss in soluble insulin, the time-actions of these components have been shown, in clinical trials, to be unaffected. The interaction between these different physical forms of insulin has been studied using reversed-phase HPLC, isothermal titrating calorimetry, and Doppler electrophoretic light scattering analysis. Sorbent surface and solution perturbation studies revealed that the NRI adsorbs to the surface of the NPH crystal with an equilibrium constant ranging from 104 M–1 to 107 M–!, depending on the protamine concentration, pH, ionic strength, and temperature. This adsorption behavior suggests that the binding is mediated by electrostatic interactions arising between the positively-charged NPH crystal and the negatively-charged NRI hexamer. Doppler electrophoretic light scattering results, used to probe the pH-dependent surface charge of NPH and soluble insulin hexamer, support the conclusion that electrostatic interactions mediate the adsorption process. Adsorption studies under physiological conditions indicate that the elevated temperature and ionic strength, in a subcutaneous depot, are sufficient to lead to the dissociation of the NRI/NPH complex that exists in these NPH mixture formulations. 相似文献
Background: The Na sup + channel is voltage gated and characterized by three distinct states: closed, open, and inactivated. To identify the effects of halothane on the cardiac Na sup + current (INa) at various membrane potentials, the effects of 1.2 mm halothane at different holding potentials (VH) on INa were examined in single, enzymatically isolated guinea pig ventricular myocytes.
Methods: The INa was recorded using the whole-cell configuration of the patch-clamp technique. Currents were generated from resting VH s of -110, -80, or -65 mV. State-dependent block was characterized by monitoring frequency dependence, tonic block, and removal of inactivation by veratridine.
Results: Halothane produced significant (P < 0.05) VH -dependent depressions of peak INa (mean +/- SEM): 24.4 +/- 4.1% (VH = -110 mV), 42.1 +/- 3.4% (VH = -80 mV), and 75.2 +/- 1.5% (VH = -65 mV). Recovery from inactivation was significantly increased when cells were held at -80 mV (control, tau = 6.0 +/- 0.3 ms; halothane, tau = 7.1 +/- 0.4 ms), but not at -110 mV. When using a VH of -80 mV, halothane exhibited a use-dependent block, with block of INa increasing from 8.6 +/- 1.4% to 30.7 +/- 3.5% at test pulse rates of 2 and 11 Hz, respectively. Use-dependent inhibition was not apparent at VH of -110 mV. When inactivation of INa was removed by exposure to 100 micro Meter veratridine, no significant difference was observed in the depressant effect of halothane at both VH s: 26.6 +/- 4.5% (VH = -80 mV) and 26.4 +/- 5.6% (VH = -110 mV). 相似文献
Nonacid plasma glycolipids from Lewis-negative individuals of nonsecretor, partial-secretor and secretor phenotypes were prepared and separated by thin-layer chromatography and immunostained with radiolabelled Lewis antibodies. Lewis-positive plasma and intestinal epithelial cell glycolipids from Caucasians representing the four recognized Lewis and secretor combined phenotypes were used as controls. By presenting these purified total glycolipids in a cell-free environment to Lewis antibodies we were able to demonstrate the presence of small amounts of Lewis antigens in Lewis-negative individuals. It is shown that lactotetraosylceramide and extended precursor glycolipids are present in all Le(a–b–) nonsecretors. Leawas detected in 1 of the 3 Le(a–b–) nonsecretor plasmas and in the intestinal sample of the same phenotype. Lactotetraosylceramide was absent but H type 1 and Lebwere both present in all group O Le(a–b–) secretors, and extended H type 1 reactive structures were also found in the partial secretor. These results clearly demonstrate that although the Lewis-negative phenotype exists at the serological level, this phenotype is not an 'all-or-nothing' phenomenon at the chemical level. We also show that in the presence of reduced fucosyltransferase activity, increased elongation of the precursor chain occurs, which allows us to postulate that fucosylation of the precursor prevents or at least markedly reduces chain elongation. 相似文献