Preliminary evidence of improvement of depressive symptoms but not impulsivity in cluster B personality disorder patients treated with quetiapine: an open label trial.

INTRODUCTION: Atypical antipsychotics might become a new treatment option for patients with an impaired impulse regulation as seen in cluster B personality disorders (PD). The aim of the present study is to investigate the efficacy and tolerability of quetiapine in patients with cluster B PD. METHODS: Fifteen in-patients with a DSM-IV diagnosis of borderline, histrionic, or narcissistic PD were treated for 8 weeks with quetiapine at a dose of 400 mg/day in an open-label fashion. Effects on impulsivity (Barratt Impulsiveness Scale, BIS), depressive symptoms (Hamilton Depression Scale, HAMD, and Beck Depression Inventory, BDI) and side effects (Dosage Record and Treatment Emergent Symptom Scale, DOTES) were assessed. RESULTS: Twelve patients completed the study. No positive effect on impulsivity (BIS) was found, but a significant improvement on depression scores (HAM-D and BDI) was noted. Adverse effects that might have been due to study medication were mainly anticholinergic and mild-to-moderate. DISCUSSION: The data of our preliminary open-label study do not argue for a general recommendation of quetiapine for the treatment of impulsivity in cluster B PD, but indicate positive effects on depressive symptoms.

Serum concentrations of nerve growth factor and brain-derived neurotrophic factor in depressed patients before and after antidepressant treatment.

INTRODUCTION: Stress, glucocorticoids and anti-depressant treatment have been found to modulate the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Recent research suggests that serum BDNF concentration is reduced in depression and that successful antidepressant treatment leads to an increase in serum BDNF concentration. METHODS: We studied depressed patients receiving a standardized antidepressant treatment with either 150 mg amitriptyline (n=20) or 40 mg paroxetine (n=20) for 36 days in a prospective design. Changes in the concentrations of serum neurotrophins and salivary cortisol in response to antidepressant treatment were assessed. RESULTS: Independent of clinical efficacy there was a significant 'treatment' by 'medication' interaction effect on BDNF serum concentrations that indicated a decline of BDNF by 12% in paroxetine-treated patients while there was an increase by 13% in amitriptyline-treated patients. Neither antidepressant altered NGF concentrations. The changes in cortisol and neurotrophin concentrations were not related. DISCUSSION: Changes in BDNF serum concentrations as a result of antidepressant therapy depend on the antidepressant instead of being a general characteristic of response to antidepressant treatment.

Cerebral endothelial cells release TNF-alpha after stimulation with cell walls of Streptococcus pneumoniae and regulate inducible nitric oxide synthase and ICAM-1 expression via autocrine loops.

TNF-alpha, inducible NO synthase (iNOS), and ICAM-1 are considered to be key proteins in the inflammatory response of most tissues. We tested the hypothesis that cell walls of Streptococcus pneumoniae (PCW), the most common cause of adult bacterial meningitis, induce TNF-alpha, iNOS, and ICAM-1 expression in rat primary brain microvascular endothelial cell cultures. We detected TNF-alpha mRNA by RT-PCR already 1 h after stimulation with PCW, while TNF-alpha protein peaked at 4 h (9.4 +/- 3.6 vs 0.1 +/- 0.1 pg/microgram protein). PCW induced iNOS mRNA 2 h after stimulation, followed by an increase of the NO degradation product nitrite (18.1 +/- 4 vs 5.8 +/- 1.8 at 12 h; 18.1 +/- 4 vs 5.8 +/- 1.8 pmol/microgram protein at 72 h). The addition of TNF-alpha Ab significantly reduced nitrite production to 62.2 +/- 14.4% compared with PCW-stimulated brain microvascular endothelial cells (100%). PCW induced the expression of ICAM-1 (measured by FACS), which was completely blocked by TNF-alpha Ab (142 +/- 18.6 vs 97.5 +/- 12.4%; 100% unstimulated brain microvascular endothelial cells). Cerebral endothelial cells express TNF-alpha mRNA as well as iNOS mRNA and release the bioactive proteins in response to PCW. PCW-induced NO production is mediated in part by an autocrine pathway involving TNF-alpha, whereas ICAM-1 expression is completely mediated by this autocrine loop. By these mechanisms, cerebral endothelial cells may regulate critical steps in inflammatory blood-brain-barrier disruption of bacterial meningitis.

Pneumococcal cell wall components induce nitric oxide synthase and TNF-alpha in astroglial-enriched cultures.

Astroglia and microglia, the most numerous cells in the central nervous system (CNS), have been shown to produce the inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) upon stimulation with the cytokines IFN-gamma, IL-1-beta, or bacterial lipopolysaccharides (LPS). However, it is not known whether gram-positive bacteria like Streptococcus pneumoniae cause astroglial cells to release nitric oxide (NO) and TNF-alpha. S. pneumoniae meningitis still has a high incidence and mortality in spite of antibiotic therapy. Cell wall components from S. pneumoniae (pneumococcal cell-wall components, PCW) and TNF-alpha have been shown to cause meningeal inflammation and cerebrovascular changes in experimental meningitis. Addition of PCW to cultured rat astroglial cells increased nitrite in the supernatant significantly after 24 h, from 17 +/- 21 to 133 +/- 62 nM/micrograms protein. Nitrite release was dose-dependent in a range shown to cause meningeal inflammation in vivo and was inhibited by the competitive NO synthase inhibitor NW-nitro-L-arginine (L-NA 10(-4 M)) and dexamethasone (10(-6 M)), with transcriptional and translational inhibition by actinomycin D and cycloheximide, respectively. PCW caused a significant increase in the release of TNF-alpha from astroglial cells after 4 h, from 2 +/- 3.5 pg/ml to 102 +/- 13.5 pg/ml, which was inhibited by dexamethasone (10(-6 M)). Our results suggest a role for astroglial-derived NO and TNF-alpha as mediators of vascular and inflammatory response in the early phase of experimental pneumococcal meningitis.

[Drug lowering of the HDL concentration in the serum of cardiologically treated patients]. / Untersuchungen zur medikamentösen Senkung der HDL-Konzentration im Serum bei kardiologisch betreuten Patienten.

The connection between decreased concentration of HDL-cholesterol in the serum and increased risk of arteriosclerosis has attracted the attention to such sizes of influence which are able to decrease the HDL-cholesterol-concentration. In these cases the question is asked, whether the analytic reliability of the techniques which are at the disposal for the estimation of HDL-cholesterol is sufficient for the recognition of the changes of the concentration to be expected. To the sizes of influence belong medicaments which cannot be fancied away in the therapy of cardiovascular diseases; thus the beta-receptor blockers talinolol and propranolol. The examination of 118 cardiologically treated patients yields the result that there is no particular risk of the patients treated by means of these medicaments, since an essential decrease of the HDL-cholesterol-concentration could not be proved.