Study on the possible interaction between tenoxicam and atenolol in hypertensive patients.

Sixteen hypertensive male out-patients (33-54 y), whose blood pressure (BP) had been normalized (diastolic BP < 90 mmHg) by treatment with a daily dose of 50 mg atenolol (CAS 29122-68-7), participated in this double-blind, placebo-controlled, parallel group study, which investigated the possible influence of the non-steroidal anti-inflammatory drug tenoxicam (CAS 59804-37-4) on the control of BP by atenolol. After a run-in of 10 days, to assess the stability of BP control by atenolol, and to determine baseline parameters, 8 patients in group A received 20 mg tenoxicam (2 x 20 mg on days 1 and 2), and 8 patients in group B received placebo, daily over 15 days (days 0-14), concomitantly with their atenolol regimen. BP was measured under standardized conditions on several days. Heart rate (EHR) after 5 min of exercise by bicycle ergometry (constant 75W), and parameters of renal function were assessed before (baseline) and during concomitant dosing of atenolol and tenoxicam. On day 14 the mean changes (delta A, delta B) from baseline of pre-dose BP (mmHg) and EHR (beats/min) in groups A and B, and the one-sided 95% confidence regions (R) for delta A, respectively, were (delta A, delta B, R): 4.4, 1.6, < 9.5 for sitting systolic BP, 2.8, -0.3, < 4.5 for sitting diastolic BP, -0.3, -0.6, < 5.5 for standing systolic BP, -0.6, -1.9, < 3.0 for standing diastolic BP, 0.4, -7.5, < 0.4 for EHR at pre-dose, 3.1, 0.6, < 7.8 for EHR at 3.5 h post-dose.(ABSTRACT TRUNCATED AT 250 WORDS)

The behaviour of various platelet function tests during long-term prostacyclin infusion in patients with peripheral vascular disease.

In 20 patients with peripheral vascular disease treated with prostacyclin (5 ng/kg/min) we observed a significant activation of platelet function as measured by platelet proteins, ADP-induced aggregation platelet sensitivity and platelet count. Only the platelet survival was significantly prolonged by the treatment.

Decreased sensitivity of human platelets to PGI2 during long-term intraarterial prostacyclin infusion in patients with peripheral vascular disease--a rebound phenomenon?

During successful treatment of peripheral vascular disease with synthetic prostacyclin no alteration in platelet function was reported (1). In 8 patients infused with synthetic prostacyclin continuously for 7 days intraarterially, the platelet function was monitored. Special attention was drawn to the platelet sensitivity in vitro for PGI2, which is discussed as an important factor maintaining the hemostatic balance. In all the patients with peripheral vascular disease between 24 and 48 hours after the beginning of the infusion a sudden decrease in platelet sensitivity accompanied by an increase in platelet count could be seen. These dramatic alterations representing probably a rebound phenomenon occurring during long-term PGI2-treatment might be an explanation for a non-beneficial effect of the treatment and in some cases a limiting factor for the continuation of the infusion itself. It is not clear, if this rebound phenomenon is due to a stimulation of an endogenous inhibitor, lowering the synthesis of a naturally occurring substance acting against this inhibitor or tachyphylaxia.

Early atherosclerotic lesions in rat aorta. Effect of cholesterol feeding and immunization.

Germ-free and conventional rats were fed cholesterol or normal pellets and part of both groups were immunized repeatedly with horseradish peroxidase (HRP). Four days after the last injections all the rats were killed, aortas removed and prepared for immunocytology and chemical analysis. Free peroxidase was not detected in the arterial wall and in all immunized rats only faint staining of free anti-HRP antibodies occurred in the intima. In contrast there was a consistent deposition of HRP-anti-HRP antibody complexes in the inner two thirds of the arterial wall in all HRP-immunized animals. Immunization and cholesterol feeding increased the cholesterol content of the aorta and produced early lesions, whereas cholesterol feeding or immunization alone was less effective.

Removal of fatty acid labelled cholesterol ester, phospholipid and triglyceride from atherosclerotic rabbit aorta in vitro.

An organ culture technique was used to investigate the removal of fatty acids incorporated into various lipid fractions in intimal segments of atherosclerotic rabbit aorta. Segments of aorta were pulse-labelled in vitro with [9,10-3H]oleic acid and [1-14C]linoleic acid for 24 h. The incubation medium was replaced with non-radioactive medium and the removal of the endogenously labelled phospholipid, triglyceride and cholesterol ester was followed for a further period of 10 days. Fatty acids incorporated into phospholipid and triglyceride were removed rapidly from the aortic intima, with fractional half-times of 4--5 days. Cholesterol ester fatty acids were removed more slowly from the aortic intima with fractional half-times of 9--12 days. When the removal rate of oleic acid incorporated into phospholipid, triglyceride and cholesterol ester was compared with that of linoleic acid incorporated into the same lipid fractions, no difference between removal of the two fatty acids could be detected with respect to any of the 3 lipid fractions.

[Long-term tissue culture of normal and atherosclerotic human arterial explants (author's transl)]. / Langfristige Gewebekultur von menschlichen normalen und atherosclerotischen Arterienexplantaten.

A method for longterm tissue culture of human arterial explants is described. The explants of normal and atherosclerotic femoral arteries, removed immediately post mortem, were kept in culture for up to 14 days in a biochemically active state. Viability was checked by glucose uptake and lactate production, with daily changes of incubation media and sterility controls. Compared to the well established short term incubation systems where metabolic activity decreases progressively after 6 h, glucose uptake, lactate production and uptake of 3H-oleic acid are linear within 4-14 h. The highest incorporation of 3H-oleic acid is found in phospholipids, the lowest in cholesterol ester. But whilst activity, after the pulse label of 24 h, progressively decreases in phospholipids, it constantly increases in the cholesterol ester fraction as a consequence of the persistant cholesterol esterification.

Uptake and metabolism of 3H-fatty acid labelled lecithin by normal and atherosclerotic intima in vivo and in vitro.

Following the intravenous injection of tracer doses of 3H-fatty acid labelled lecithin into normally fed rabbits, minimal incorporation into serum cholesterol ester over a 6-hour period was observed. The labelled phospholipid was rapidly removed from the serum primarily by R.E. tissues with little uptake by the aorta. The uptake and metabolism of 3H-fatty acid labelled lecithin by explants of normal and cholesterol-fed rabbit aortas was also investigated in vitro for periods up to 8 days. Low uptake and incorporation into cholesterol ester was observed for the normal aortic explants. The labelled phospholid was taken up to a greater extent by explants from cholesterol-fed rabbit aortas and the fatty acid incorporated into both triglyceride and cholesterol ester in the explants. The incorporation of fatty acid into cholesterol ester from phospholipid was associated with hydrolysis of the phospholipid and re-incorporation of the fatty acid into cholesterol ester, rather than by the action of lecithin cholesterol acyl transferase.

[Panarteritis nodosa-Special aspects of glucocorticoid and immune suppressive therapy (author's transl)]. / Panarteriitis nodosa. Therapie mit Glukokortikoiden und Immunsuppressiva

Report dealing with the clinical and pathoanatomical course as well as the autopsy findings in a 54 year old female suffering from panarteritis nodosa. Onset of the illness with polyneuritis and arthralgia. One year later diagnosis of panarteritis nodosa verified by muscle biopsy. Deterioration of the disease leading to the development of peripheral gangrene could not be prevented in spite of intensive therapy with steroids, immune suppressive agents, digitalis and antihypertensive drugs. Death 4 years later by myocardial infarction. Autopsy revealed generalized healed panarteritis nodosa with scarring and obliteration of vessels. A short description of the symptoms of the disease is given and the efficacy of the therapy with steroids and immune suppressive drugs is discussed from the clinical as well as the pathoanatomical point of view. Immunopathologic mechanisms are considered to be the responsible factors for pathogenesis.

Lipid metabolism of the arterial wall in thromboangiitis obliterans (Buerger's disease).

The uptake and incorporation of [I14-C] oleic acid by diseased arterial intima removed by thrombendarteriectomy in 3 patients with Thromboangiitis obliterans (TAO) was studied. The diagnosis of TAO had been established by clinical, angiographic and histological criteria. The uptake and distribution of the label was found very similar in TAO and normal intima and differed considerably from atherosclerotic intima, from fatty streaks as well as from fibro-fatty lesions. In fatty streak lesions the incorporation of [I14-C] oleic acid into phospholipid, triglyceride and cholesterol ester was significantly increased compared to TAO, normal intima and unbilical artery. In TAO the distribution of labeled lipids between subcellular fractions of the arterial intima was also studied and, as in normal intima, most of the cholesterol ester were found membrane-bound whereas in fibro-fatty lesions the bulk of the cholesterol ester was present in the lipid skin fraction. The incorporation of [I14-C] oleic acid into different phospholipids was highest in atherosclerotic intima while no significant differences were found between normal intima and TAO. These data suggest a different pathogenesis of TAO and atherosclerosis.