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Notes: Summary 1. Receptor protection experiments were carried out in cerebrocortical slices from rabbits in order to study the sites at which drugs with α-adrenoceptor affinity modulate the release of noradrenaline. The slices were preincubated with 3H-noradrenaline. They were then superfused with 3H-noradrenaline-free medium and stimulated electrically (3 Hz) twice for 2 min each, after 60 and 250 min of superfusion (S1, S2). Phenoxybenzamine was added from 85 to 95 min of superfusion. Potential protecting drugs were present for 5 min before and during the exposure to phenoxybenzamine and then washed out together with the latter. 2. Phenoxybenzamine 0.1 and 1 μmol/l increased the evoked overflow of tritium by 77 and 287%, respectively, as indicated by the S2/S1 overflow ratio. When cocaine was present throughout superfusion, phenoxybenzamine 0.1 and 1 μmol/l increased the evoked overflow by 97 and 353%, respectively. 3. Clonidine 0.1–100 μmol/l, when added before and during the contact with phenoxybenzamine, reduced or even abolished the increase caused by the latter. This interaction was not changed when cocaine was included in the superfusion fluid. The increase caused by phenoxybenzamine was also reduced or abolished by noradrenaline 1–100 μmol/l (tested in the presence of cocaine), yohimbine 0.01–1 μmol/l and phentolamine 0.1–10 μmol/l. Only high concentrations of clonidine, noradrenaline, yohimbine and phentolamine changed the evoked overflow when given alone (and subsequently washed out). 4. The effect of phenoxybenzamine was not modified by prazosin 1 μmol/l, morphine 1 μmol/l and naloxone 10 μmol/l. 5. The opioid agonists ethylketocyclazocine 0.1–10 μmol/l, bremazocine 0.1 and 1 μmol/l and dynorphin A (1–13) 0.1 and 1 μmol/l reduced but never abolished the overflow-enhancing effect of phenoxybenzamine. The three compounds always depressed the evoked overflow of tritium when administered alone (and subsequently washed out). They failed to counteract phenoxybenzamine in otherwise identical experiments in which naloxone 10 μmol/l was either present throughout superfusion or added to the medium 95 min after the end of the exposure to phenoxybenzamine and the opioid agonists. 6. It is concluded that drugs with affinity for α2-adrenoceptors protect the noradrenergic axons of rabbit brain cortex against the long-lasting release-enhancing effect of phenoxybenzamine. No protection is afforded by drugs with affinity for α1-adrenoceptors or opioid μ-receptors. The decrease in the effect of phenoxybenzamine caused by selective opioid κ-agonists is not due to receptor protection but to the activation of presynaptic opioid receptors which then may somehow interfere with the operation of (neighbouring?) presynaptic α2-adrenoceptors. The site protected by clonidine, noradrenaline, yohimbine and phentolamine is the same site at which these compounds themselves and, by inference, endogenous noradrenaline modify transmitter release, namely the presynaptic α2-autoreceptor.

Notes: Summary From 1984 to 1991 20 multiple trauma patients with pelvic fractures and retroperitoneal bleeding from pelvic vessels underwent angiographic localization and embolization of massively bleeding arterial vessels. Nine patients survived (multiple trauma index grade III, Hanover polytrauma index), three patients with very severe injuries died immediately (multiple trauma index grade IV). After successful control of bleeding by embolization, three other patients died from severe brain injuries and five patients from septic multiorgan failure. The interval to definite localization and treatment of the bleeding source was three times shorter in the group of survivors, and the amount of transfusions needed was less by a factor of three. This underlines the importance of early angiography in multiple trauma patients with pelvic fractures and persisting hemorrhage. Embolization has proven to be effective in the treatment of such injuries.

Notes: Summary The interaction between presynaptic, release-inhibiting α 2-adrenoceptors and opioid receptors was studied in slices of the parieto-occipital cortex of rabbits. The slices were preincubated with 3H-noradrenaline and then superfused with 3H-noradrenaline-free medium and stimulated electrically (3 or 7 Hz, 2 or 5 V/cm voltage drop between the electrodes). Clonidine and ethylketocyclazocine (EK) depressed, whereas yohimbine increased the electrically evoked overflow of tritium. When clonidine was administered first and retained in the medium for the rest of the experiment, the overflow-inhibiting effect of EK was reduced. When yohimbine was administered first and kept for the rest of the experiment, the effect of EK was enhanced. When, finally, EK was adminstered first and clonidine as the second drug, the overflow-inhibiting effect of clonidine was attenuated. The changes in the effect of EK (by clonidine or yohimbine) and clonidine (by EK) were not due to the changes in release per se produced by the drugs that were given first. Naloxone shifted the concentration-response curve of EK to the right; the dissociation constant of the naloxone-receptor complex, calculated from the shift, was 13 nmol/l. It is concluded that there is an interaction between presynaptic α 2-adrenoceptors and opioid к-receptors, either at the level of the receptors themselves or of the post-receptor reaction chains. Activation of one kind of receptor blunts the inhibition of release produced by activation of the other kind of receptor.

Notes: Summary 1. Receptor protection experiments were carried out in order to study the site of action of α-adrenoceptor agonists and antagonists on the release of noradrenaline. Cerebrocortical slices from rabbits were preincubated with 3H-noradrenaline. They were then superfused with medium containing cocaine 30 μmol/l and stimulated electrically (3 Hz) three times, after 60, 250 and 295 min of superfusion (S1, S2, S3). Phenoxybenzamine 10 μmol/1 when used, was added between S1 and S2 for 30 min; putative protecting drugs (clonidine 100 μmol/1 or yohimbine 10 μmol/1) were present 5 min before and during the exposure to phenoxybenzamine and then washed out together with the latter. Either the voltage drop between the electrodes at S2 and S3 or the Ca2+-concentration of the superfusion medium at S2 and S3 was diminished, if necessary, in order to bring the overflow evoked by S2 close to the overflow at S1. Blockade by phenoxybenzamine, or protection against the blockade, was examined by addition of the test compounds noradrenaline 0.1 μmol/1 or yohimbine 1 μmol/1 before S3. 2. In slices not exposed previously to α-adrenoceptor ligands, noradrenaline 0.1μmol/1 greatly reduced, whereas yohimbine 1 μmol/1 greatly increased the evoked overflow of tritium. Both effects were abolished in slices treated with phenoxybenzamine 10 pmol/1 alone between S1 and S2. 3. In contrast to phenoxybenzamine alone, exposure to phenoxybenzamine 10 μmol/1 in the presence of either clonidine 100 pmol/1 or yohimbine 10 μmol/1 failed to abolish the effects of the test compounds noradrenaline 0.1 μmol/1 and yohimbine 1 μmol/1, although the effects were reduced. 4. It is concluded that the irreversible antagonist phenoxybenzamine, the protecting agents clonidine and yohimbine, the test compounds noradrenaline and yohimbine, and by inference endogenous noradrenaline as well, all act at the same site, namely the presynaptic α-autoreceptor.

Notes: Abstract We investigated the role of three different signal transduction systems adenylate-cyclase (AC), protein kinase C (PKC) and tyrosine kinase (TK) for growth and invasion of a human follicular (FTC 133) and a human papillary thyroid cancer cell line (PTC-UCI). Cyclic AMP stimulators and inhibitors had no effect at any concentration. The PKC agonist TPA enhanced both growth and invasion of FTC133 by 15%, whereas staurosporine, a PKC antagonist, inhibited growth by 47% and invasion by 32%. The latter also reversed thyrotropin (TSH) stimulation, but not epidermal growth factor (EFG) stimulation. EGF-stimulated growth and invasion of both cell lines were abolished by EGF-receptor antagonism using a monoclonal antibody. The tyrosine kinase antagonist genistein reversed EGF, but not TSH, stimulation. Pertussis toxin inhibited growth (FTC133: 22%) and invasion (FTC133: 18%). Cholera toxin was less inhibitory. Obviously, signal transduction of differentiated thyroid cancer is complex and systems other than adenylate cyclase are crucial for basal invasion and growth of follicular thyroid cancer cells in culture.

Notes: Summary Between 1955–1985 515 patients with carcinoma of the thyroid have been operated. Among 170 cases with a local infiltration 69 tracheostomies were performed in 55% for lesions of both laryngeal nerves or intratracheal bleeding (absolute indication), in 45% as a prophylactic intraoperative procedure to avoid later death from asphyxiation (relative indication). In a retrospective study clinical results were analysed with special reference to the question whether patients profit by the tracheostomy. Follow-up examinations showed that tracheostomy did not influence the outcome of patients with a differentiated thyroid carcinoma while there was a remarkable difference in survival of patients with anaplastic tumors where those with a tracheostomy had a worse survival. In this group postoperative external radiotherapy often could not be administered or was delayed due to local complications of the tracheostoma.