Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction.

Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory.

Impact of propofol on mid-latency auditory-evoked potentials in children.

BACKGROUND: Propofol is increasingly used in paediatric anaesthesia, but can be challenging to titrate accurately in this group. Mid-latency auditory-evoked potentials (MLAEPs) can be used to help titrate propofol. However, the effects of propofol on MLAEP in children are unclear. Therefore, we investigated the relationship between propofol and MLAEP in children undergoing anaesthesia. METHODS: Fourteen healthy children aged 4-16 yr received anaesthesia for elective surgery. Before surgery, propofol was administered in three concentrations (3, 6, 9 µg ml(-1)) through a target-controlled infusion pump using Kataria and colleagues' model. MLAEPs were recorded 5 min after having reached each target propofol concentration at each respective concentration. Additionally, venous propofol blood concentrations were assayed at each measuring time point. RESULTS: Propofol increased all four MLAEP peak latencies (peaks Na, Pa, Nb, P1) in a dose-dependent manner. In addition, the differences in amplitudes were significantly smaller with increasing propofol target concentrations. The measured propofol plasma concentrations correlated positively with the latencies of the peaks Na, Pa, and Nb. CONCLUSIONS: Propofol affects MLAEP latencies and amplitudes in children in a dose-dependent manner. MLAEP measurement might therefore be a useful tool for monitoring depth of propofol anaesthesia in children.

[Isovolemic hemodilution for avoiding homologous blood transfusions: effectiveness in large gynecologic interventions]. / Isovolämische Hämodilution (IHD) zur Einsparung von Fremdbluttransfusionen: Effektivität bei grossen gynäkologischen Eingriffen.

OBJECTIVE: The practicability and efficiency of a standardized, preoperative isovolemic hemodilution was investigated during major gynecological operations (Wertheim's operation, etc.). DESIGN: Prospective clinical trial with a historical control group. SETTING: Operating room of a gynecological university hospital. PATIENTS AND INTERVENTIONS: Under general anesthesia hemodilution to a hemoglobin concentration of 9 g/dl was performed in 48 patients (mean age: 53 years). Shed blood volume amounted to 900 +/- 210 ml. Transfusion of autologous or homologous blood was provided when Hb concentration decreased beyond 7 g/dl intraoperatively. RESULTS: Compared to a control group of 57 patients without hemodilution the total number of PRBC units transfused was significantly reduced. Moreover, in 65% of all patients the transfusion of homologous blood could completely be avoided perioperatively (control group: 21% of patients). Adverse effects did not occur. CONCLUSIONS: The data reflect that acute isovolemic hemodilution before major gynecological operations represents a safe, easy to handle and effective procedure to avoid transfusion of homologous blood up to a total blood loss of 1,300-1,400 ml.

Occlusion of a branch of the central retinal artery by a corpus alienum as a rare complication of the carotid arteriography.

This report concerns a 43-year-old female patient, complaining of a film over the eye after carotid arteriography. Ophthalmoscopical examination showed an occlusion of a branch of the central retinal artery just at the nasal border of the optic disc with a slight blurring at the edge of the papilla in this area. Retinal edema was found in the supporting area of the arteria temporalis inferior and the visual field shows, accordingly, a lost sector. Endogenous embolism is discussed here in contrast to an exogenous one as well as its causes.