The handling of five amines by the extraneuronal deaminating system of the rat heart

Summary The handling of five amines by the extraneuronal deaminating system was studied in perfused hearts of rats (pretreated with reserpine; COMT and neuronal uptake inhibited). Hearts were perfused with 50 nmol/l ³H-noradrenaline for 30 min, in the presence of increasing concentrations of unlabelled (–)-adrenaline, (–)-noradrenaline, dopamine, tyramine and 5-HT. IC₅₀'s were determined as those concentrations of unlabelled amines which halved the steady-state rate of deamination of ³H-noradrenaline. After correction for changes in the tissue/medium ratio for ³H-noradrenaline, half-saturating outside concentrations were obtained. They increased in the order (–)-adrenaline (15 mol/l) — tyramine — dopamine — noradrenaline —5-HT (53 mol/l). The V _max for extraneuronal deamination was determined for ³H-(–)-adrenaline, ³H-(–)-noradrenaline and ³H-dopamine, as well as (by HPLC and electrochemical detection) for tyramine and 5-HT. It was low for (–)-adrenaline, intermediate for (–)-noradrenaline, dopamine and 5-HT, high for tyramine. For the three catecholamines the half-saturating outside concentrations of the extraneuronal deaminating system clearly exceeded those for the extraneuronal O-methylating system of the same organ (see Grohmann and Trendelenburg 1985), although the two enzymes appear to co-exist in the same cells, so that the same transport system is involved.Abbreviations COMT catechol-O-methyl transferase - DOMA dihydroxymandelic acid - DOPEG dihydroxyphenylglycol - 5-HT 5-hydroxytryptamine - MAO monoamine oxidase Supported by the Deutsche Forschungsgemeinschaft (SFB 176) Send offprint requests to U. Trendelenburg     

The behaviorally active peptide ACTH 4-10: Measurement in plasma and pharmacokinetics in man

Summary A specific radioimmunoassay for the quantitative measurement of ACTH 4-10 and a procedure for its extraction from plasma have been developed.Its pharmacokinetics was studied in eight healthy male volunteers given ACTH 4-10 125 µg/kg body weight as a bolus i.v. injection, by infusion and intranasally. Following the i.v. bolus, plasma levels rapidly declined biexponentially, with half-lives of 0.39±0.05 min for the -phase and 3.84 ± 1.5 min for the -phase (mean±SD). The constant rate i.v. infusion yielded steady-state levels between 0.74 and 5.06 ng/ml plasma. Administered as intranasal spray, absorption of intact ACTH 4-10 was low and variable (maximal bioavailability 7.6%).The results are discussed in relation to the dose-dependent effects of ACTH 4-10 on the auditory evoked potential.     

The value of a zero power intraocular lens

An intraocular lens with a reversed optic and with haptics angulated forward presses the posterior capsule more posteriorly than other types of lenses. This position is thought to be important even in eyes that do not need intraocular lenses for optical reasons, such as eyes with high axial myopia (because of their increased tendency to postoperative retinal detachment) and eyes with postoperative capsular fibrosis. "Zero lenses" were implanted in seven eyes. The lenses had a convex posterior surface and a concave anterior surface which were parallel. The position of the posterior capsule, measured with ultrasound, was 4.9 mm to 5.8 mm (mean 5.5 mm) behind the anterior corneal surface. In two fellow eyes without a lens (after planned extracapsular cataract extraction), the posterior capsule was 4.1 mm and 4.3 mm behind the anterior corneal surface.     

The uptake and O-methylation of 3H-(±)-isoprenaline in rat cerebral cortex slices

Summary The O-methylation and accumulation of ³H-isoprenaline in slices of the rat cerebral cortex were studied before and after inhibition of COMT. 1. Inhibition of COMT by mol/l U-0521 virtually abolished the O-methylation and increased the accumulation of ³H-isoprenaline; hence, there is evidence for the existence of a central O-methylating system (with a transport mechanism and intracellular COMT). 2. Experiments were carried out with selective uptake inhibitors for uptake, (cocaine and desipramine) or uptake2 (corticosterone and OMI), with phenoxybenzamine (known to inhibit both carriers) and with changes in the ionic composition of the incubation medium. They revealed that the central carrier differed from both, uptake, and uptake2, although exhibiting some resemblance with uptake₂ (lack of dependence on Na⁺ and Cl^–, sensitivity to K⁺ and phenoxybenzamine, ability to transport ³H-isoprenaline). 3. Although the central carrier was rather sensitive to inhibition by beta-adrenoceptor antagonists (propranolol, carteolol), the effect of propranolol was not stereoselective; hence, beta-adrenoceptors do not seem to be involved. 4. Virtually identical IC₃₀-values were obtained for inhibitors, when determined with or without inhibition of COMT. Only OMI was found to inhibit COMT as well as the central transport system; hence it was more potent in inhibiting the O-methylation than the accumulation of ³H-isoprenaline. 5. IC₅₀-values (against initial rates of accumulation of ³H-isoprenaline; COMT inhibited) were determined for various substrates and inhibitors of peripheral uptake₂. There was no correlation with the IC₅₀-values determined earlier for uptake2 in rat heart (Grohmann and Trendelenburg 1984). 6. Unlabelled catecholamines half saturated the intracellular COMT when slices were incubated with 0.22 mol/l [(±)-dobutamine] to 4.9 mol/l [(–)-noradrenaline]. As the presence of unlabelled catecholamines increased tissue levels of ³H-isoprenaline, catecholamines are substrates of the central carrier. 7. The carrier of the central O-methylating system differs from uptake₂ of peripheral organs, although it resembles the peripheral carrier in some respects.Abbreviations COMT catechol-O-methyl transferase - DOPEG dihydroxyphenylglycol - MAO monoamine oxidase - OMI 3-Omethyl-isoprenaline Supported by the Deutsche Forschungsgemeinschaft (Tr 96 and SFB 176) and by a scholarship of the Royal Society for V. G. Wilson. Some of the results were presented to the British Pharmacological Society (Trendelenburg and Wilson 1986)     

Preauricular pilomatrixoma: a diagnostic pitfall

Although pilomatrixomas are well known to dermatologists and dermatopathologists, surgeons encountering these lesions over the parotid gland frequently do not consider this benign neoplasm in the differential diagnosis. Presentation of a subcutaneous preauricular lesion, coupled with an erroneous cytologic diagnosis of malignancy, can potentially result in histologic "overdiagnosis" and more aggressive therapy than is required for these benign hair follicle neoplasms. A case is reported to illustrate this potential diagnostic trap, and a series of 206 cases collected at the University Hospital of Zurich from 1975 to 1987 is reviewed.     

Comparison of the chelating capacity of EDTA and EGTA, a new demineralized agent, on molars in vitro

Recent morphologic studies have shown qualitative, how demineralizing substances clean teeth roots. In this work we attempt to describe quantitatively the "chelation process" and pH evolution of the quelator solution in-vitro inside the teeth during the reaction. These results indicate that Ca++ coming from hydroxyapatite release protons from EDTAH under neutral conditions. This is the most likely mechanism of the "self-limitation". Furthermore, it allow us to explain why EDTA Im and EGTA Im were more efficient than EDTA Na and EGTA Na upon demineralizing the tooth. EGTA Im turn out to be the fastest demineralizing agent as compared to EDTA Na which is currently employed in endodontic therapy.     

Relative sensitivity of four noninvasive methods in assessing systolic cardiovascular effects of isoproterenol in healthy volunteers.

STUDY OBJECTIVE: The study was performed to evaluate the relative sensitivity of various noninvasive methods to detect and describe the systolic cardiovascular effects of stepwise increasing doses of isoproterenol: two-dimensional left ventricular echocardiography (main variable, ejection fraction), ACVF (attenuation compensated volume flow)--dual-beam Doppler echoaortography (time-averaged mean velocity), electrical impedance cardiography [(dZ/dtmax)/RZ index], and systolic time intervals from mechanocardiography (PEP and QS2c). METHODS: Isoproterenol was administered by constant rate intravenous infusion in consecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 micrograms/min (each for 15 minutes). Saline control infusions were given in analog fashion. The treatments (isoproterenol and saline solution) were administered in a period-balanced two-way crossover design with randomly allocated sequences. The subjects, observers, and analysts were blinded to the treatment protocol. Study subjects were 10 healthy male volunteers (age range, 23 to 31 years; mean age, 26.6 years). RESULTS: Compared with saline solution, isoproterenol caused a dose-related increase in ejection fraction, (dz/dt)/RZ index, and time-averaged mean velocity and a dose-related shortening of PEP and QS2c. The responses are congruent with an enhancement of cardiac systolic performance caused by a positive inotropic stimulation and an afterload reduction ("inodilatory" response). The effects on systolic time intervals reached statistical significance (alpha = 0.05) at the first isoproterenol dose step, the effects on the impedance cardiography and the Doppler echoaortography variables reached statistical significance at the second dose step, and the effects on the two-dimensional echocardiography reached statistical significance at the third dose step. CONCLUSIONS: All methods allowed to detect isoproterenol-related changes. Systolic time intervals were the most sensitive, followed by impedance cardiography, ACVF--dual-beam Doppler echoaortography, and two-dimensional echocardiography. The practical convenience and high sensitivity of the systolic time intervals makes them suitable to evaluate investigational systolic inodilatory changes in humans.     

Haemostyptic preparations on the basis of collagen alone and as fixed combination with fibrin glue

Preparations containing collagen play a prominent role among local haemostyptic agents in surgery. Sheets of collagen are used as degradable haemostyptic tampons. Various investigations have shown better haemostasis with collagen compared to other degradable materials, although the haemostyptic effect of these collagen preparations is limited. Concerning the mechanism of haemostasis, not all the reactions stimulated, e.g. by the collagen of an injured vessel wall, may be activated by a haemostyptic tampon from collagen. This depends very much on the kind of preparation. The combined application of a sheet of collagen with fibrin glue improved local haemostasis to a great extent. Large areas of capillary bleeding can be treated successfully with this method. Despite the very good results, this method has not been applied on a broad scale. This is due to the necessary skill and experience and the relatively cumbersome preparation required at the operation site. These drawbacks have been overcome with the latest development in this field--a sheet of collagen covered with a fixed layer of the solid components of a fibrin glue (fibrinogen, thrombin and aprotinin). The performance of this new local haemostyptic agent is described with special emphasis on the results of clinical trials. Haemostasis of large areas of capillary bleeding was very efficient and safe with the new material. Moreover, bile leakage and liquor, pancreatic and aerial fistulae could be sealed without problems.