Effects of Anesthetic Agents on Focal Adhesion Kinase (pp125FAK) Tyrosine Phosphorylation in Rat Hippocampal Slices

Background: Tyrosine protein kinase proteins exert a prominent control on signaling pathways and may couple rapid events, such as action potential and neurotransmitter release, to long-lasting changes in synaptic strength and survival. Whether anesthetics modulate tyrosine kinase activity remains unknown. The aim of the current study was therefore to examine the effects of intravenous and volatile anesthetics on the phosphorylation of focal adhesion kinase (pp125FAK), a functionally important nonreceptor tyrosine kinase, in the rat hippocampus.

Methods: Phosphorylation of pp125FAK was examined in hippocampal slices by immunoblotting with both antiphosphotyrosine and specific anti-pp125FAK antibodies. Experiments were performed in the absence (control) or presence of various concentrations of pharmacologic or anesthetic agents or both.

Results: Clinically relevant concentrations of thiopental, propofol, etomidate, isoflurane, sevoflurane, and desflurane induced a concentration-related increase in tyrosine phosphorylation. In contrast, ketamine (up to 100 [mu]m) and the nonimmobilizer F6 (1,2-dichlorohexafluorocyclobutane, 25 [mu]m) did not significantly affect pp125FAK phosphorylation. The anesthetic-induced increase in pp125FAK phosphorylation was blocked by GF 109203X, RO 318220, and chelerythrin (100 [mu]m), three structurally distinct inhibitors of protein kinase C and U 73122 (50 [mu]m), an inhibitor of phospholipase C. The propofol- and isoflurane-induced increase in pp125FAK phosphorylation was reversible and showed nonadditivity of effects with phorbol 12-myristate 13-acetate (an activator of protein kinase C, 0.1 [mu]m). In contrast, ketamine (up to 100 [mu]m), MK801 (10 [mu]m, an N-methyl-d-aspartate receptor antagonist), bicuculline (10 [mu]m, a [gamma]-aminobutyric acid type A receptor antagonist), and dantrolene (30 [mu]m, an inhibitor of the ryanodine receptor) were ineffective in blocking anesthetic-induced activation of tyrosine phosphorylation.     

Proportion and predictors of Hypogonadism Recovery in Men with Macroprolactinomas treated with dopamine agonists

Pituitary - Hypogonadism is the most common form of hypopituitarism in men with macroprolactinoma. However, evidence on factors related to hypogonadism recovery is limited. We estimated the...     

Structural correlates underlying accelerated magnetic stimulation in Parkinson's disease

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique with great potential in the treatment of Parkinson''s disease (PD). This study aimed to investigate the clinical efficacy of accelerated rTMS and to understand the underlying neural mechanism. In a double‐blinded way, a total of 42 patients with PD were randomized to receive real (n = 22) or sham (n = 20) continuous theta‐burst stimulation (cTBS) on the left supplementary motor area (SMA) for 14 consecutive days. Patients treated with real cTBS, but not with sham cTBS, showed a significant improvement in Part III of the Unified PD Rating Scale (p < .0001). This improvement was observed as early as 1 week after the start of cTBS treatment, and maintained 8 weeks after the end of the treatment. These findings indicated that the treatment response was swift with a long‐lasting effect. Imaging analyses showed that volume of the left globus pallidus (GP) increased after cTBS treatment. Furthermore, the volume change of GP was mildly correlated with symptom improvement and associated with the baseline fractional anisotropy of SMA‐GP tracts. Together, these findings implicated that the accelerated cTBS could effectively alleviate motor symptoms of PD, maybe by modulating the motor circuitry involving the SMA‐GP pathway.     

An individual scoring system for the prediction of postpartum anaemia

Background

Postpartum anaemia (PPA) is a common postpartum complication. The goal of this study was to prospectively construct a predictive score for individual risk of PPA.

Patients et method

We prospectively analyzed factors associated with PPA (< 10 g dL⁻¹ at 48 hours postpartum). Parameters analyzed were demographic data, pregnancy characteristics, delivery and postpartum characteristics. Univariate analysis was performed using Anova or X²; the Cox model was used for multivariate analysis. The scoring system was validated using ROC curve.

Results

Analysis was performed in 475 patients and validation was carried using an additional 95 patients. Multivariate analysis found four factors independently associated with PPA: anaemia during the third trimester of the pregnancy, Southeast Asian ethnic origin, episiotomy and severe postpartum haemorrhage (PPH) identified by the use of sulprostone. According to the score derived from the Cox model, patients were classified as low (22%, score = 0), medium (55%, score = 2 or 3) and high (86%, score > 3) probability of PPA. Using the AUC of the ROC curve for both the first and the validation cohorts (performed on 95 further patients), we recorded AUCs of 72% and 70% respectively.

Conclusions

This study allowed the derivation and validation of a predictive score of PPA. This score might be useful in targeting prophylactic strategies for PPA. Such strategies could include a more active treatment of iron deficiency (increasing oral iron treatment observance or intravenous iron therapy) especially in exposed population, improvement in the prevention and treatment of postpartum haemorrhage and decreasing the use of episiotomy. Future studies must focus on the external validation and generalisation of this scoring system.