Effects of exercise stress on the endocannabinoid system in humans under field conditions.

The effects of physical exercise stress on the endocannabinoid system in humans are almost unexplored. In this prospective study, we investigated in a crossover design and under field conditions at different altitudes the effects of physical exercise on the endocannabinoid system (ECS) in 12 trained healthy volunteers. For determination of alterations on the ECS three different protocols were analyzed: Protocol A (physical exercise at lower altitude) involved strenuous hiking below 2,100 m, whereas Protocol B (physical exercise by active ascent to high altitude) involved hiking up to 3,196 m, an accommodation at the cottage and a descent the next day. Protocol C (passive ascent) included a helicopter ascent to 3,196 m, an overnight stay at this altitude and a flight back to the base camp the following day. The cumulative hiked altitude in Protocol A and B was comparable (~1,650 m). The blood EC concentrations of anandamide increased significantly in Protocol A/B from baseline (T0) 0.12 ± 0.01/0.16 ± 0.02 (mean ± SEM) to 0.27 ± 0.02/0.42 ± 0.02 after exercise (T1) (p < 0.05). Anandamide levels in Protocol C remained stable at 0.20 ± 0.02. We conclude that the ECS is activated upon strenuous exercise whereas the combination with hypoxic stress further increases its activity. The reduced partial pressure of oxygen at high altitude alone did not affect this system. In summary, physical exercise activates the endocannabinoid system, whereas the combination with high altitude enhances this activation. This discloses new perspectives to adaptation mechanisms to physical exercise.

[Subcutaneous preservation of an amputated auricle. Morphological changes]. / Subkutane Konservierung einer abgetrennten Ohrmuschel. Morphologische Veränderungen.

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.

[Isolation and receptor binding properties of alkaloids and lignans from Valeriana officialis L]. / Isolierung, Strukturaufklärung und Radiorezeptorassays von Alkaloiden und Lignanen aus Valeriana officinalis L.

In addition to the known Valeriana-Meanalkaloid, four 7,9':7'9-Diepoxylignans were isolated from the roots of Valeriana officinalis L. They were tested in different radioreceptorassays at the 5-HT1A-, GABAA-, benzodiazepin and mu-opiate-receptor.

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.

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.

[Nifedipine prolongs a neuromuscular blockade caused by atracurium]. / Nifedipin verlängert eine neuromuskulre Blockade durch 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.

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.

[Further acylated chalcones from Bidens pilosa]. / Weitere acylierte chalkone aus Bidens pilosa.

Three new acylated chalcone glucosides [okanin 4'- O-beta- D-(4''-acetyl-6''- TRANS- P-coumaroyl)-glucoside, okanin 4'- O-beta- D-(2'',4''-diacetyl-6''- TRANS- P-coumaroyl)-glucoside, and okanin 4'- O-beta- D-(3'',4''-diacetyl-6''- TRANS- P-coumaroyl)-glucoside] have been isolated from the leaves of BIDENS PILOSA L. (Asteraceae). Their structures have been elucidated by spectroscopic methods ( (1)H-NMR, 2D- (1)H-NMR, (13)C-NMR spectroscopy).

New Chalcones from Bidens pilosa.

Okanin 4'- O-beta- D-(2'',4'',6''-triacetyl)-glucoside, okanin 4'- O-beta- D-(6''- TRANS-P-coumaroyl)-glucoside, both new natural compounds, and okanin 3'- O-beta- D-glucoside have been isolated from the leaves of BIDENS PILOSA L. Their structures have been elucidated by means of UV, FD-MS, (1)H-NMR, and (13)C-NMR spectroscopy. NMR spectral data for okanin 4'- O-beta- D-glucoside (marein) are given.

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.

[Absorption, distribution and metabolism of [14C]-levomenol in the skin]. / Resorption, Verteilung und Metabolismus von [14C]-Levomenol in der Haut.

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.

Biflavonoids in Hypericum perforatum1; Part 1. Isolation of I3, II8-Biapigenin.

From the Soxhlet extract of HYPERICUM PERFORATUM, biflavonoids have been isolated by column chromatography on Sephadex LH 20 and preparative TLC. The structure of the main compound was elucidated by UV-, (1)H- and (13)C-NMR spectroscopy and MS as I3,II8-Biapigenin.