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Biomedical subjects

J Hölzl

Publications and source records attributed to J Hölzl.

At least 19 recordsLinked to original sources

[Subcutaneous preservation of an amputated auricle. Morphological changes].

BACKGROUND: Microsurgical replantation of an avulsed auricle remains a challenge in reconstructive surgery. Secondary reconstruction of a traumatic lost auricle is usually performed using a costal cartilage framework according to well documented techniques or with a prosthesis. In order to minimize donor-site morbidity, various efforts can be undertaken to preserve the amputated auricle by implanting the de-epithelialized cartilage framework in a subcutaneous pocket on the surface of the mastoid. Where preservation is successful, this original cartilage could be used for reconstructive treatment. PATIENT AND RESULTS: This study describes the histologic and immunohistologic changes in a complete traumatic avulsion of the auricle with subsequent cartilage conservation for eight months within a skin pocket. Trauma, preparation and preservation were accompanied by morphologic changes that included generation of local ossification centers and infiltration of fibrous tissue. We compared the macroscopic and microscopic morphology of the amputated part to native elastic cartilage following maximal denutrition and temporary heterotopic implantation in conjunction with atypical tension and pressure properties of the retroauricular pocket. CONCLUSION: In this case, the limited success of cartilage conservation in the subcutaneous pocket required conventional auricle reconstruction with autologous costal cartilage.

Adult↗

Functional and antiischaemic effects of Monoacetyl-vitexinrhamnoside in different in vitro models.

1. Functional and antiischaemic effects of monoacetyl-vitexinrhamnoside (AVR), a flavonoid with phosphodiesterase (PDE)-inhibitory properties contained in Crataegus species (Hawthorn, Rosaceae) were studied in several in-vitro models. 2. In rabbit isolated femoral artery rings, AVR concentration-dependently reduced developed tension. Vasodilation by AVR was reduced after inhibiting EDRF formation by L-NG-nitro arginine. 3. In spontaneously-beating Langendorff-guinea pig hearts, AVR concentration-dependently enhanced heart-rate, contractility, lusitropy and coronary flow. 4. In isolated electrically-driven Langendorff-rabbit hearts, acute regional ischemia (MI) was induced by coronary artery occlusion and quantified from epicardial NADH-fluorescence photography. AVR (5 x 10(-5) mol/l) induced a slight numerical increase of left ventricular pressure and coronary flow (p > 0.05). MI was reduced (p < 0.05). 5. Monoacetyl-vitexinrhamnoside is an inodilator whose vasodilatory action may be mediated in part by EDRF in addition to PDE-inhibition. Monoacetyl-vitexinrhamnoside does possess marked antiischemic properties even in isolated hearts, suggesting an improvement of myocardial perfusion.

Abortifacient Agents↗

Myocardial effects of flavonoids from Crataegus species.

The influence of the main flavonoids from Crataegus species (hawthorn, Rosaceae) on coronary flow, heart rate and left ventricular pressure as well as on the velocity of contraction and relaxation was investigated in Langendorff perfused isolated guinea pig hearts at a constant pressure of 70 cmH2O. Drug action was evaluated in a concentration range of 10(-7) to 5 x 10(-4) mol/l. An increase of coronary flow caused by the O-glycosides luteolin-7-glucoside (186%), hyperoside (66%) and rutin (66%) as well as an increase of the relaxation velocity (positive lusitropism) by luteolin-7-glucoside (104%), hyperoside (62%) and rutin (73%) were the major effects observed at a maximum concentration of 0.5 mmol/l. Furthermore, slight positive inotropic effects and a rise in heart rate were seen. Similar but less intensive actions were found with the C-glycosides vitexin, vitexin-rhamnoside and monoacetyl-vitexin-rhamnoside. Possible beta-adrenergic activities of the flavonoids could be excluded by the addition of propranolol in fixed concentrations of 10(-8) to 10(-5) mol/l. Moreover, pretreatment of the animals with reserpine (7 mg/kg) did not influence myocardial activity of hyperoside (10(-4) mol/l). As previous experiments showed an inhibition of the 3',5'-cyclic adenosine monophosphate phosphodiesterase, the results suggest an inhibition of this enzyme as the possible underlying mechanism of cardiac action of flavonoids from Crataegus species.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Nifedipine prolongs a neuromuscular blockade caused by atracurium].

Calcium entry blockers are now widely employed in the treatment of cardiovascular diseases and perioperative hypertension. In patients with coronary heart disease nifedipine therapy should be continued perioperatively to avoid coronary artery spasm. Animal experiments have demonstrated that calcium entry blockers potentiate the neuromuscular blockade induced by nondepolarizing blocking agents. In patients, an atracurium-induced neuromuscular depression is prolonged by intravenous nifedipine. In this prospective clinical study we evaluated the effect of chronic oral nifedipine therapy on the duration of neuromuscular block by atracurium. Sixty patients anaesthetized with isoflurane in nitrous oxide/oxygen were recruited for this study. Thirty of these were on chronic oral nifedipine therapy and received their normal morning dose before premedication. The control consisted of 30 patients of similar age and status but not taking any calcium entry blockers. Monitoring included noninvasive blood pressure, heart rate, pharyngeal temperature, physical breathing parameters and neuromuscular transmission with a Datex Relaxograph TM ("train of four"-principle). After inducing hypnosis 0.5 mg/kg atracurium were administered for muscular relaxation. The duration of block from administration of the relaxant to recovery of first twitch height (T1) to 25% of control twitch height was registered as duration of initial block. When T1 reached 25% a repetition dose of 0.2 mg/kg atracurium was injected. The time till recovery of T1 to 25% was recorded as the duration of the repetition dose. Results were compared using Student's t-test for unpaired data. There was a significant prolongation of the duration of initial block from 38 min +/- 10 min in the control group to 46 min +/- 8 min in the therapy group (P < 0.01). The duration of the repetition dose rose from 30 min +/- 8 min in the control group to 38 min +/- 7 min in the therapy group (P < 0.001). Daily nifedipine doses varied from 10 mg in the morning to 40 mg divided into single doses with no influence on the prolongation of neuromuscular block. Our results confirm previous assumptions of synergistic effects of nifedipine and neuromuscular blocking drugs in patients. Chronic oral nifedipine therapy potentiates neuromuscular blockade by atracurium as does nifedipine intravenously. This effect should be considered in the treatment of cardiovascular diseases with nifedipine in the perioperative period.

Aged↗

Vasoactive properties of procyanidins from Hypericum perforatum L. in isolated porcine coronary arteries.

Procanidin fractions (PC) were isolated from Hypericum perforatum L. (Guttiferae). Characterization of the main components of each fraction was performed by UV- and mass spectroscopy. Their biological activity was tested in porcine isolated coronary arteries. All PC fractions antagonized histamine- or prostaglandin F2 alpha-induced arterial contractions. In contrast, vasorelaxation was insignificant in KCl-precontracted coronary arteries except with the higher oligomeric PC fraction 3. Vasoactive properties of the PC seem to be dependent on their relative molecular mass. An inhibition of cellular phosphodiesterase might be involved in the underlying mechanism of action.

Animals↗

Insulin receptor kinase defects as a possible cause of cellular insulin resistance.

The insulin receptor contains in its beta-subunit a tyrosine (-) specific protein kinase. It is believed that transmission of an insulin signal across the plasma membrane of target cells of insulin action occurs through activation of this kinase, autophosphorylation of the insulin receptor beta-subunit and subsequent phosphorylation of other cellular substrates. We studied the insulin receptor kinase in a number of insulin resistant cell systems in order to elucidate if defects of this kinase are a possible cause of cellular insulin resistance. Three different patterns of kinase abnormalities were found, in different insulin resistant cells: 1. In an insulin resistance melanoma cell line a reduced receptor kinase autophosphorylation was found apparently due to a defect of the tyrosine autophosphorylation sites of this receptor; 2. Catecholamine and phorbol ester induced insulin resistance of isolated rat fat cells as well as human fat cells was associated with a decreased activity of the insulin receptor tyrosine kinase which was apparently due to a modulation of the ATP binding site of the insulin receptor tyrosine kinase; 3. The receptor kinase isolated from the skeletal muscle of diabetic Zucker rats (fa/fa) was found to be insulin insensitive with no major alteration of maximal responsiveness. These results suggested that different forms of kinase defects exist which can contribute to the pathogenesis of cellular insulin resistance. Based on these data studies in skeletal muscle from type II diabetic patients were started. Results from five patients so far suggest that, here as well, an abnormality of the insulin receptor kinase exists which might be involved in the pathogenesis of insulin resistance in type II diabetes.

Adipose Tissue↗

[Absorption, distribution and metabolism of [14C]-levomenol in the skin].

The purpose of the present investigations was to study the cutaneous absorption of sesquiterpenic alcohol, the major active principle of chamomile. For these investigations 14C-labelled levomenol ((-)-6-methyl-2-(4-methyl-3-cyclohexen-1-yl)-5-hepten-2-ol; (-)-alpha-bisabolol) was prepared by biochemical incorporation of [14C]-acetate into the molecule. 5 h after topical application of the radiolabelled substance onto nude mice half of the radioactivity was found in the skin. The other part was measured in tissue and organes. 90% of this radioactivity was analysed as intact levomenol. To demonstrate the distribution of the substance in the skin a part of this tissue was cutted into horizontal slices by a cryotome. From the slices autoradiograms were produced. The densitometric measuration showed that there was a fast penetration of levomenol into the skin. 5 h after the topical application the substance was displaced from outermost to innermost areas. From these results a fast cutaneous absorption and a long therapeutical effect of the antiphlogistic and spasmolytic levomenol in the skin can be expected.

Administration, Topical↗

Protein kinase activity of the insulin receptor from muscle.

The insulin receptor is associated with a protein kinase activity. This has been shown for the receptor of liver, fat, and some other tissues which are not primary targets of insulin action. Here kinase activity is demonstrated for the insulin receptor of rat skeletal and cardiac muscle with similar characteristics. Insulin (10(-7) mol/l) stimulates phosphorylation of the 95-kDa receptor subunit 3- to 18-fold. The effect is detectable at 10(-10) mol/l insulin; the ED50 is approx. 3 X 10(-9) mol/l. The kinase phosphorylates exogenous substrate as well, and it is recovered after immunoprecipitation of the receptor with antireceptor antibody suggesting that kinase activity is intrinsic to the muscle receptor.

Actins↗

[Effect of valeprotriate on spontaneous motor activity in mice].

The purpose of the present investigation was to study effects of valtrate and acetoxyvaltrate hydrine on locomotor activity of mice. The method is characterized by the control of single animals over two total periods of activity. A differentiated effect curve caused by the substances during 24 h was maintained and an effect by doses used in therapy became evident. Locomotor activity was significantly inhibited by valtrate in a concentration of 0.1 mg/kg injected i.v. and 0.5 mg/kg if applied p.o. Higher concentrations did not result in an elongated effect. Acetoxyvaltrate hydrine, which is characterized by missing epoxide structure, caused reduced locomotor activity in a concentration of 4 mg/kg.

Animals↗

[The effects of valtrate on the EEG of the isolated, perfused rat brain].

The purpose of the present investigation was to prove the central activity of valtrate. In order to avoid biotransformation of valtrate the isolated perfused rat brain was used for this study. The CNS activity of the drug was characterized by EEG changes which were analysed visually and quantified by automatic methods. The following results were obtained: In the EEG of brains perfused with valtrate the normal background beta activity was interrupted by spikes and paroxysmal patterns of theta frequencies. These patterns disappeared after reperfusion with the control medium without drug. Valtrate reduced the beta activity and produced an increase in the theta and delta frequencies of the EEG. Using valtrate concentrations of 0.1-100 mumol/l in the perfusion medium a clear dose-response relationship was not demonstrable.

Animals↗

[Pharmacology of potential antidepressants of the N-L-phenylalanyl-beta-phenylalkylamine class].

The spectrum of the pharmacological activities of N-L-phenylalanyl L-2-amino-1-phenylpropane (13), the most active representative of the investigated L-N-phenylalanyl-beta-phenylalkylamines 11-20, comprises adrenergic (noradrenaline potentiation on the vas deferens of the rat, tetrabenazine antagonism in the mouse), as well as cholinergic blocking (acetylcholine antagonism on the jejunum of the rat, oxotremorine antagonism in the mouse, anti-aggressive activity in isolated mice) and localanesthetic properties (inhibition of conduction in the ventricular strip of the frog heart) as described for antidepressants. In its pharmacological behavior 13 meets rather an antidepressant than a psychotonic drug. The conception of a partial metabolic liberation of the latent amphetamine component in 13 and a certain contribution of amphetamine to the effect of 13 is supported by the fact that at higher dosages a shortening of the hexobarbital narcosis and an increase of the spontaneous activity in mice is seen.

Animals↗

[Investigations of pharmacokinetics and metabolic behavior of N-L-pnenylalanyl-L-2-amino-1-phenylpropane (author's transl)].

To elucidate the pharmacokinetic and metabolic behavior of N-L-phenylalanyl-L-2-amino-1-phenylpropane (7), which resembles antidepressants in its pharmacological spectrum, 14C-labelled 7 was synthesized. After i.p. application of 7 to the mouse on accumulation in the gastrointestinal tract, liver, kidney, bile and brain was shown by autoradiograms of the whole body. In the mouse 7 is excreted predominantly by the kidney (54% of the applied 14C-activity 8 h p.i.) and also considerably with the feces (11% of the applied 14C-activity 8 h p.i.). After 48 h the clearance is largely completed (85% of the applied 14C-activity). In the mouse the maximum 14C-activity in the brain (1.87% of the applied 14C-activity) is already reached after 0.25 h, 93.38% of it consisting of 7 and of amphetamine (5) liberated from 7, quantity ratio 5:7 = 1.43, and 5.00% hydroxylated metabolites of 5. With decreasing concentration of 5 and 7 the quantity ratio of 5:7 reaches a maximum value of 3.56 after 4 h. The steadily raised spontaneous motility by 7 after i.p. application lasting 4 h is attributed to 5, which is antagonized by 7. Due to pharmacokinetic and pharmacological data 5 and 7 are discussed as originators of the adrenergic effects of 7.

Aminopeptidases↗