Largely applied to internal threading of extruded tubes, cold form tapping is now becoming a promising process for internal threading of holes in non ferrous and ferrous solid components, more particularly for mass production in the automotive industry. The aim of this study is to present the surface properties of the threads resulting from form tapping. Geometrical characterization, surface texture, mechanical and metallurgical observations are investigated. The results obtained are discussed according to the input parameters of the process, and are compared to those obtained from cut tapping. The strength of the work material and the influence of the lubricant are the two main parameters affecting the process, and a correlation with the tapping torque is proposed. Finally, the characteristics of the thread surface depend on the parameters of the tapping operation, thus it has to be taken into account in the design approach when this tapping process is chosen.

The bioavailability of orally administered drugs can be influenced by interactions with food components and by physico-chemical conditions in the upper gastrointestinal tract. Normally, bile salts enhance the transport of lipophilic drugs across mucosal membranes. Bile salts are able to form stable mixed micelles consisting of fatty acids and phospholipids. Conventional micellar systems are known to solubilize lipophilic drugs having a low bioavailability. The influence of bile salts and mixed micelles on the pharmacokinetics of the lipophilic drug quinine was investigated in rabbits. Female rabbits were given intraduadenally quinine (5 mg/kg body weight) without and with incorporation into the micellar or mixed micellar systems. Blood was collected every 30 min for 6 h. In plasma, concentration of quinine was measured using HPLC. The plasma concentration-time profiles of quinine were significantly lower within the first 2 h after administration in presence of both the sodium salt of glycodeoxycholic acid (above the critical micellar concentration) as well as of mixed micellar systems consisting of glycodeoxycholic acid and palmitic acid and/or lecithin. The pharmacokinetic parameters AUC (relative bioavailability) and c(max) of quinine were significantly decreased by micellar systems in rabbits. These mixed micellar systems lower and not as expected, increase the absorption of quinine in vivo. Therefore, quinine should be orally administered at least 1h before food intake, particularly before fat intake.

Largely applied to internal threading of extruded tubes, cold form tapping is now becoming a promising process for internal threading of holes in non ferrous and ferrous solid components, more particularly for mass production in the automotive industry. The aim of this study is to present the surface properties of the threads resulting from form tapping. Geometrical characterization, surface texture, mechanical and metallurgical observations are investigated. The results obtained are discussed according to the input parameters of the process, and are compared to those obtained from cut tapping. The strength of the work material and the influence of the lubricant are the two main parameters affecting the process, and a correlation with the tapping torque is proposed. Finally, the characteristics of the thread surface depend on the parameters of the tapping operation, thus it has to be taken into account in the design approach when this tapping process is chosen.

In a model of rat heart anaphylaxis, the effects of high versus low dexamethasone doses were examined in dependence on time of administration and on co-administration of the glucocorticoid receptor antagonist RU 486.Dexamethasone doses of 0.1 - 10 mg/kg given i.p. 2 h before heart perfusion caused a significant improvement of the anaphylaxis-impaired heart parameters. Simultaneous administration of the glucocorticoid receptor antagonist RU 486 (40 mg/kg) with dexamethasone significantly inhibited the improvement in contractility but not in heart rate and coronary flow. When given immediately before perfusion only the glucocorticoid megadose (10 mg/kg) caused an improvement of the parameters measured.Summarizing the present investigations it can be said that high glucocorticoid doses may act via a non-genomic mechanism.

Glucocorticoids are the most potent antiinflammatory drugs. Large doses of dexamethasone and other glucocorticoids are widely used in the clinic but the mechanism of the beneficial effects of megadoses still remains to be explained. We tested the effects of a dexamethasone (DEX) megadose therapy in a rat model of anaphylactic shock. By combining DEX with the potent glucocorticoid receptor antagonist RU 486 we looked for evidence of a non-specific action of the glucocorticoid at high doses. A dose of 10 mg/kg DEX given 2 h before challenge protected the heart against the symptoms of cardiac anaphylaxis: heart rate was improved by 22%, ventricular contractility by 13% and coronary flow by 5%. Administration of 20 mg/kg RU 486, 30 min before dexamethasone, reduced the beneficial effect of DEX by about 30%, although this failed to reach statistical significance. We found no dose-response relationship for the high dexamethasone doses of 0.5-10 mg/kg. In experimental allergic encephalomyelitis (EAE) there was a surprising toxic action of DEX after daily doses of 0.25 mg/kg for 5 days, and also following single administration of 2.5 or 10 mg/kg. A single dose of 1.25 mg/kg, given on the day of immunization alone or with additional doses at weekly intervals for 3 weeks, caused a strong inhibition of the EAE. In summary we conclude that the present data of cardiac anaphylaxis hardly point to extra glucocorticoid megadose effects. The present dexamethasone effects in cardiac anaphylaxis and in EAE have to be cleared up by further experiments.

The steroid-saving activity of the highly potent new non-steroid antiinflammatory agent CGP 28238 was determined in rat carrageenin paw edema and in primary phase of adjuvant arthritis in comparison with indomethacin. Both nonsteroidal agents showed independent synergistic effects with dexamethasone. Thereby, both compounds reduced the dose of the glucocorticoid necessary for equieffective inhibition of inflammation in the same dose range.

1. Parameters of isolated hearts from rats which were actively sensitized to ovalbumin were found to be impaired on ovalbumin challenge: the heart rate increased whereas the contractility force and coronary flow decreased significantly.2. Treatment in vivo or in vitro with histamine receptor antagonists (promethacine and cimetidine), the leukotriene antagonist FPL 55712, the PAF antagonist BN 52021, the combined prostaglandin endoperoxide receptor antagonist/thromboxane A2 synthesis inhibitor R 68070, dagger the thromboxane synthetase inhibitor HOE 944, the lipoxygenase inhibitor ZIMET 47/79, the antioxidant sodium hyposulfite or with dexamethasone caused a different improvement of the parameters to a different degree.3. Consequently, histamine, leukotrienes, PAF, activated oxygen, thomboxane A2 and possibly further autocoids might be involved in mediating the described anaphylactic reaction.