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Introduction: There is no data available on the action of etomidate on ion currents in human neuronal cells. Therefore the effects of etomidate on a human neuronal delayed rectifier potassium current were investigated., Method: Outward rectifying potassium currents of human neuroblastoma SH-SY5Y cells were measured using the whole cell patch-clamp technique. Cells were grown in RPMI-medium (+Pen/Strep and FCS) at 37 degrees C and 5% CO2. The holding potential was -80 mV. Potassium currents were evoked by depolarizing the membrane potential to values from -50 mV to +90 mV in 10 mV steps using an EPC-7 patch-clamp amplifier (List medical electronics) and pclamp version 5.71 (Axon instruments)., Results: Etomidate differentially inhibited steady-state and peak potassium current with IC50-values of 170 microM for peak current suppression and 120 microM for steady-state current respectively. Etomidate induced inactivation-like behaviour of the potassium current and changed the voltage dependence of potassium current activation., Conclusion: The results demonstrate that etomidate has more than one effect on the potassium current, indicating the complexity of general anaesthetic actions on neuronal targets. The actions of etomidate on human neuronal potassium currents may potentially contribute to the myocloni observed with this general anaesthetic agent during induction of anaesthesia.

We studied the effect of thyroxine (T4 0.050 mg/kg/d, i.p.), TSH (0.08 U/kg/d, i.p.) and hypothalamic peptide (HF; 1 mg protein/kg/d, i.p.) given alone or in combination, on the growth of murine (NB C-1300) and human (NB Park) neuroblastoma transplanted onto the nude mouse (nu/nu). Both T4 and TSH caused a significant increase (perchlorate a decrease) of the serum T3. Histologically, the T4 treatment was followed by partial tumor necrosis and a marked growth of connective tissue within the tumors; there was no significant change in tumor weight as compared to the control group. Treatment with HF alone or in combination with T4 inhibited in 30% the invasive growth of the neuroblastoma transplants and a fatty degeneration was found in 25% of the human NB-TX after 28 days of treatment. The measurement of the intratumoral content of the cyclic nucleotides showed a significant increase of the cAMP and a decrease of the cGMP. The morphological and biochemical alteration observed under treatment with thyroid hormone or analogues could possibly be applied for therapeutic purposes.

The action of the (-)- and (+)-enantiomers of the beta-adrenoceptor blocking drug propranolol on the inward calcium current (ICa) was studied in single mouse neuroblastoma x rat glioma hybrid cells of clone 108CC5 by suction pipette technique for intracellular perfusion and voltage clamp. ICa was recorded after internal cell perfusion with Tris phosphate buffer and suppression of sodium and potassium currents in Na+-free external solution. Extracellularly applied (-)- and (+)-propranolol (10(-7) to 10(-3) M) inhibited ICa in a similar dose-dependent manner. The IC50 values for both substances were approximately 5 . 10(-6) to 10(-5) M. Two other beta-blockers, alprenolol and talinolol, investigated as reference compounds, also depressed the ICa, but in a significantly higher dose-range of 10(-4) to 10(-3) M. The results provide further evidence that propranolol, besides its known effect on sodium inward current, also possesses marked inhibitory actions on the ICa in mammalian nerve cell membranes at relatively low concentrations.

The diagnosis of bilateral neuroblastoma in the adrenal glands in a newborn led to the discovery of a family with clustering of tumors of neural crest origin. According to the two-mutation model of neuroblastoma development we searched for individuals with the first mutation, who are predisposed to neuroblastoma. Neither chromosomal analysis of the peripheral blood nor the examination of catecholamines nor of gm-phenotypes could mark the first step to neuroblastoma. However, it was possible to detect cystationinuria in familial neuroblastoma for the first time. Cystationinuria could be calssified as secondary to vitamin B6-deficiency. Since cystathioninuria and vitamin B6-deficiency were not only seen in blood-relations but also in relatives by marriage there was no fixed correlation to individuals with tumor or their relatives.