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.     

Extracorporeal Photopheresis for the Treatment of Cutaneous T-Cell Lymphoma

Journal of Cutaneous Medicine and Surgery -     

Partial vertical laryngectomies and reconstruction with plathysma myocutaneous flap

The authors report on 14 patients with epidermoid carcinoma of the glottic region, classified T1, T2 and T3, operated upon by a hemilaryngectomy (9 cases) with reconstruction using a Plathysma myocutaneous flap. The oncological results over a follow-up period of 1 to 6 years and the functional results are analyzed. The authors conclude that this method does not compromise the carcinological result and provides a good functional result with low ratings for complications, with in addition an adequate support for the organ, favouring increased resections.     

Incidence of bladder cancer in a cohort of workers exposed to 4-chloro-o-toluidine while synthesising chlordimeform.

Between 1982 and 1990 seven cases of bladder cancer were detected in a group of 49 workers who were synthesising chlordimeform from 4-chloro-o-toluidine. Latency periods ranged from 15 to 23 years. The incidence of bladder tumours in this group was significantly higher than that of the cancer registers of the former GDR, Saarland, and Denmark by factors of 89.7, 53.8, and 35.0 respectively. This provides further evidence that monocyclic aromatic amines such as 4-chloro-o-toluidine may be carcinogenic in humans.