Effects of antidepressant treatment on gene expression profile in mouse brain: cell type-specific transcription profiling using laser microdissection and microarray analysis.

A gene expression study of mice treated with the tricyclic antidepressant amitriptyline was performed. To enable the detection of cell type-specific expression changes, laser-microdissected nucleus accumbens was analysed after 4 and 28 days of treatment. After 4 days of treatment no significantly regulated genes could be detected in this study. In contrast, 95 genes exhibited different expression levels in animals treated for 28 days with amitrityline compared with sham animals. This observation reflects the long-term effects and adaptation processes observed in patients treated with this drug. Among the regulated genes are receptors belonging to the dopamine-dependent signalling cascade, ion channels (mainly voltage-dependent potassium and calcium channels) potentially involved in signalling cascades and neuropeptides. The results support the hypothesis that the therapeutic effect of this antidepressant is much more complex and not confined to a reuptake inhibition of neurotransmitters. Paradigms inducing only weak expression changes, which may be limited to certain cell types within the highly complex brain structure, can therefore be reliably investigated by applying a cell type-specific expression profiling technique based on laser microdissection and subsequent RNA amplification followed by DNA microarray analysis.

[Does fentanyl or midazolam improve patient's comfort and cooperation when given for regional catheter placement? A randomized, controlled and double-blind trial]. / Verbessern intravenöses Fentanyl oder Midazolam vor Durchführung einer peripheren Regionalanästhesie Patientenakzeptanz und Kooperativität bei der Katheteranlage? Eine randomisierte, placebokontrollierte und doppelblinde Untersuchung.

BACKGROUND: The procedure of placing a catheter for continuous regional anaesthesia is often associated with fear and pain in the patient. Thus, we evaluated the use of midazolam and fentanyl to improve patient's comfort and cooperation. METHODS: After an oral dose of 20 mg clorazepate, 174 patients receiving peripheral nerve catheters for regional anaesthesia where randomized into 3 groups to receive either intravenous placebo, 3 mg midazolam or 0.1 mg fentanyl immediately before catheter placement in a double-blind manner. Stepwise regression analysis was used to identify factors associated with patient's assessment of subjective discomfort (measured using a VAS 0-10) during the procedure. Amnesia was evaluated 24 h later. The anaesthetist rated patient's cooperation during catheter placement. RESULTS: Female sex and longer duration of catheter placement had significant negative impact on patient's comfort, whereas fentanyl showed an improvement. Age, body mass index, midazolam and the type of catheter had no influence. The following day 27% of the midazolam group, 6% of the placebo group and 9% of the fentanyl patients did not remember catheter placement. Patient's cooperation was poor in 26% of the midazolam patients but only in 9% of the placebo and 3% of the patients receiving fentanyl. Of the placebo patients 18.4% had to be supplemented with fentanyl because they found the procedure of catheter placement unbearable. No side effects occurred in either group. CONCLUSION: As patient's comfort and cooperation were significantly improved by fentanyl, we recommend fentanyl to facilitate catheter placement for regional anaesthesia.

Role of heteromer formation in GABAB receptor function.

Recently, GBR1, a seven-transmembrane domain protein with high affinity for gamma-aminobutyric acid (GABA)B receptor antagonists, was identified. Here, a GBR1-related protein, GBR2, was shown to be coexpressed with GBR1 in many brain regions and to interact with it through a short domain in the carboxyl-terminal cytoplasmic tail. Heterologously expressed GBR2 mediated inhibition of adenylyl cyclase; however, inwardly rectifying potassium channels were activated by GABAB receptor agonists only upon coexpression with GBR1 and GBR2. Thus, the interaction of these receptors appears to be crucial for important physiological effects of GABA and provides a mechanism in receptor signaling pathways that involve a heterotrimeric GTP-binding protein.

Analysis of antibody responses directed against two Onchocerca volvulus antigens defined by monoclonal antibodies.

Monoclonal antibodies, reactive with antigens solubilised from the body wall of intact female Onchocerca volvulus using 2% 2-beta-mercaptoethanol, have been characterised. Two IgG1 antibodies, Cam1 and Cam28, recognised antigens of apparent molecular weights of 18,000 and 28,000; and 120,000, respectively. The target antigens of Cam1 and Cam28 could be localised in the cuticle. Inhibition ELISAs showed that target epitopes of both monoclonal antibodies induce an antibody response in onchocerciasis patients. 153 sera from Sierra Leonean patients were tested for their individual antibody levels against antigen epitopes recognised by Cam1 and Cam28. Patients within the age of 5-8 years had the highest levels of antibodies against the Cam28-epitope, whereas patients above 60 years had almost none. Amicrofilaremic patients had higher anti-Cam28 antibody levels than microfilaremic patients and there was a significant difference between groups with no chronic skin disease and those with mild or severe signs. A high percentage of patients (80.4%) recognised the Cam1-epitope, highest antibody levels being found in patients within the age group of 15 to 45 years and in microfilaremic patients. However, levels of antibodies inhibiting monoclonal antibody Cam1 could not be correlated with presence or absence of skin disease.

Plateletpheresis with the new COBE Spectra.

The COBE Spectra was evaluated in 71 plateletpheresis procedures. Using the collection and anticoagulant algorithms of the system (n = 57) we collected 4.3 +/- 1.2 x 10(11) platelets with a mean separation efficiency of 70.2 +/- 12.1%. The cell contamination was very low (leukocytes 0.5 +/- 1.0 x 10(7), red cells 1.5 +/- 2.2 x 10(7]. In four different modifications of the standard separation protocols, we tried to reduce the ACD consumption in order to shorten the donation time and to improve donor safety. A constant ACD/blood ratio of 1:9 and increase of the blood flow to 50 ml/min (n = 14) caused significantly lower yields (3.1 +/- 0.7, p less than 0.01) and visible spontaneous platelet aggregates in the collection line in 50% and in the PC's in 29% of the runs. In order to prevent platelet activation the ACD algorithm had to be maintained, but a reduction of the ACD/blood ratio to about 15% was acceptable.