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101.
Mizrahi R Bagby RM Zipursky RB Kapur S 《Progress in neuro-psychopharmacology & biological psychiatry》2005,29(5):859-864
BACKGROUND: While much is known about the neuropharmacology and objective efficacy of antipsychotics, little is known about how these drugs act on psychosis from the patients' perspective. Most previous studies of the patient's perspective have focused on drug tolerability and acceptability-rather than their effects on psychosis per se. METHODS: The authors examined how antipsychotics work from a patient's perspective by analyzing their responses to a subjective questionnaire. Ninety-one patients with schizophrenia (cross-sectional component) and eight neuroleptic na?ve patients (before and after treatment, longitudinal component) participated. The patients' responses to the questionnaire were analyzed using Principal Component Analysis (PCA) and general linear models. RESULTS: Analysis of the patients' responses showed that from their perspective the drugs were substantially more effective in: "help deal, help stop thinking, and make the symptoms not bother" rather than "take away" or "change my mind". This differentiation was clear in the raw data and was supported by a formal PCA. Two underlying factors-the first termed detachment and second eradication-explained 71% of the variance in the patients' perspective on how antipsychotics work for them. Neuroleptic na?ve patients, who had no prior exposure, expected drugs to help with both detachment and eradication, but, changed their mind with just 6 weeks of experience with the medications. CONCLUSIONS: From the patients' perspective the action of antipsychotics is best characterized by a detachment from symptoms-rather than an eradication or elimination of symptoms. They have more wide-ranging expectations prior to antipsychotic exposure, but, even 6 weeks of exposure is sufficient to change their mind in favor of detachment. This finding is consistent with some of the very earliest ideas that antipsychotics produced a state of "indifference" and is also consistent with the more recent, neurobiologically informed notions that antipsychotics work by dampening the salience of psychotic symptoms. 相似文献
102.
Bender L Spalton DJ Uyanonvara B Boyce J Heatley C Jose R Khan J 《Journal of cataract and refractive surgery》2004,30(10):2058-2063
PURPOSE: To describe a new method of measuring posterior capsule opacification (PCO) and intraocular lens (IOL) rotation and report the validation of the method. SETTING: Ophthalmology Department, St. Thomas' Hospital, and Medical Imaging, Department of Physics, King's College, London, United Kingdom. METHOD: A new interactive software program, POCOman, was developed for the semiobjective assessment of PCO. Digital images of the posterior capsule, which can be acquired by any technique, are analyzed by the observer to determine the percentage area of PCO and assign a severity score. The system was validated by comparing it to clinical slitlamp evaluation of PCO and automated POCO system analysis using a library of 100 images taken from archives. The software also measures sequential IOL rotation for the evaluation of toric IOLs. RESULTS: An image could be analyzed in approximately 2 minutes. The results of the POCOman system correlated well with the results of the automated POCO system and clinical evaluation. CONCLUSIONS: The POCOman is an effective, user-friendly system for quantifying PCO. It can be obtained for free and has advantages over other methods. 相似文献
103.
In the inner plexiform layer, amacrine cells receive glutamatergic input from bipolar cells. Glutamate can depolarize amacrine cells by activation of ionotropic glutamate receptors or mediate potentially more diverse changes via activation of G protein-coupled metabotropic glutamate receptors (mGluR5). Here, we asked whether selective activation of metabotropic glutamate receptor 5 is linked to modulation of the voltage-gated Ca2+ channels expressed by cultured GABAergic amacrine cells. To address this, we performed whole-cell voltage clamp experiments, primarily in the perforated-patch configuration. We found that agonists selective for mGluR5, including (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), enhanced the amplitude of the voltage-dependent Ca2+ current. The voltage-dependent Ca2+ current and CHPG-dependent current enhancement were blocked by nifedipine, indicating that L-type Ca2+ channels, specifically, were being modulated. We have previously shown that activation of mGluR5 produces Ca2+ elevations in cultured amacrine cells (Sosa et al., 2002). Loading the cells with 5 mM BAPTA inhibited the mGluR5-dependent enhancement, suggesting that the cytosolic Ca2+ elevations are required for modulation of the current. Although activation of mGluR5 is typically linked to activation of protein kinase C, we found that direct activation of this kinase leads to inhibition of the Ca2+ current, indicating that stimulation of this enzyme is not responsible for the mGluR5-dependent enhancement. Interestingly, direct stimulation of protein kinase A produced an enhancement of the Ca2+ current similar to that observed with activation of mGluR5. Thus, activation of mGluR5 may modulate the L-type voltage-gated Ca2+ current in these GABAergic amacrine cells via activation of protein kinase A, possibly via direct activation of a Ca2(+)-dependent adenylate cyclase. 相似文献
104.
105.
Combi R Dalprà L Malcovati M Oldani A Tenchini ML Ferini-Strambi L 《Brain research bulletin》2004,63(5):353-359
Mutations responsible for autosomal dominant nocturnal frontal lobe epilepsy have been identified in two members of the neuronal nicotinic acetylcholine receptor gene family: CHRNA4(ENFL1 locus) and CHRNB2 (ENFL3 locus) coding for alpha4 and beta2 subunit, respectively. However, mutations in these genes account for only a minority (less than 10%) of cases. For a third ADNFLE locus (ENFL2) on chromosome 15q24 the gene was not identified. The involvement of the three loci in the pathogenesis of ADNFLE was investigated in 12 unrelated Italian families, selected on the basis of anamnestic and video-polysomnographic data. Compliant family members were typed for polymorphic markers spanning the analyzed chromosome regions. Linkage analyses excluded association of all chromosome regions with ADNFLE in 72% of cases. In two, four and one families it was impossible to ascertain or exclude association with ENFL1, ENFL2, or ENFL3, respectively, however, no mutations have been detected in the nicotinic receptor genes located in these regions. These data strongly suggest that ENFL1, ENFL2 and ENFL3 are minor loci for the disease and point to the existence of at least a fourth locus for ADNFLE. 相似文献
106.
107.
Gamberale R Galmarini CM Fernández-Calotti P Jordheim L Sánchez-Avalos J Dumontet C Geffner J Giordano M 《Biochemical pharmacology》2003,66(11):2185-2191
Administration of the adenosine analogue fludarabine (FLU) in vivo induces a profound and prolonged T lymphopenia which mainly affects CD4(+) cells. To better understand the mechanistic basis underlying this preferential depletion, we analyzed the in vitro susceptibility of T cell subsets to FLU-induced apoptosis. Contrasting with observations in vivo, our results showed that treatment of peripheral blood mononuclear cells with FLU induced a higher level of apoptosis in CD8(+) than in CD4(+) T lymphocytes. This increased sensitivity of CD8(+) T cells to FLU was observed in samples from both, healthy donors and B cell chronic lymphocytic leukemia patients, and resulted in higher CD4:CD8 ratios in FLU-treated than in untreated cultures (P<0.01). Expression of factors involved in FLU transport and metabolism was then evaluated by quantitative real time-PCR in normal T cell subsets. It was found that mRNA levels of human equilibrative nucleoside transporter-1 nucleoside transporter were higher whereas deoxycytidine kinase and IMP/GMP selective 5'-nucleotidase mRNA levels were lower in CD4(+) cells. However the dCK/cN-II ratio was 2-fold greater in CD8(+) than in CD4(+) T lymphocytes, which could account for the higher apoptosis levels observed in the CD8(+) subset. These results favor the view that decreased CD4:CD8 ratios in FLU-treated patients should be attributed to differences in cell recovery and/or homing between T cell subsets. 相似文献
108.
Cellular bases of the antitumor activity of a 7-substituted camptothecin in hormone-refractory human prostate carcinoma models 总被引:2,自引:0,他引:2
109.
NMDA-NR1 and -NR2B subunits mRNA expression in the hippocampus of rats tolerant to Diazepam 总被引:1,自引:0,他引:1
The development of tolerance to the hypolocomotor effects of Diazepam (DZ) is thought to be a contingent or learning phenomenon. In previous reports, we demonstrated a positive correlation between the development of tolerance to the sedative effects of DZ and hippocampal synaptic plasticity. Furthermore, previous exposure to the drug administration context blocks both the tolerance to sedative effects of DZ and the increased hippocampal plasticity. The results of the present investigation show that the development of tolerance to hypolocomotor action of DZ (5 mg/kg/day) for 4 days results in a significant increase in the hybridization signals for mRNA for N-methyl-D-aspartate (NMDA) glutamatergic receptor NR1 and NR2B subunits in the hippocampal dentate gyrus. Furthermore, we have observed more benzodiazepine binding sites in the hippocampus of non-tolerant animals. We conclude that the increased hippocampal synaptic efficacy in DZ tolerant rats, may be NMDA receptor dependent due to an increased recombinant NR1-NR2B complex observed in the hippocampal formation of tolerant rats. 相似文献
110.