Anti-inflammatory drugs in experimental atherosclerosis. Part 6. Combination therapy with steroid and non-steroid agents.

The pathological changes which accompany enhanced cholesterol deposition in atherosclerosis include inflammatory responses mediated by the prostaglandin cyclooxygenase and lipoxygenase-leukotriene metabolite of the arachidonic acid cascade. Cortisone suppresses arachidonic acid release, whereas non-steroid anti-inflammatory drugs inhibit principally the cyclooxygenase enzyme. Groups of New Zealand white rabbits were fed a 1% cholesterol diet for 12 weeks. Diets of selected groups were further supplemented daily with the non-steroid anti-inflammatory drugs phenylbutazone (100 mg), oxyphenylbutazone (240 mg), flufenamic acid (100 mg), either singly or in combination with cortisone acetate (10 mg or 5 mg), or 9-alpha-fluorohydrocortisone (30 micrograms or 200 micrograms). Serum lipid levels were measured at 0, 4, 8 and 12 weeks, and atherosclerotic plaque intensity in thoracic aorta was measured at 12 weeks using a planimetric technique: serum cholesterol levels in control groups increased from 38 +/- 5 to 1190 +/- 139 mg/100 ml. Neither the rate of increase nor the final lipid values attained were significantly changed by the non-steroid drugs. The non-steroid drugs reduced plaque coverage by about one third (phenylbutazone 34 +/- 10%, flufenamic acid 36 +/- 11%) compared to controls. In combination therapy, addition of cortisone acetate resulted in further plaque suppression. Cortisone 10 mg + phenylbutazone gave 100% suppression; cortisone 5 mg + phenylbutazone gave 82 +/- 18%, and cortisone 5 mg + flufenamic acid gave 84 +/- 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

[Possibilities for pain reduction by the prevention of edemas and elimination of endogenous pain producing substances]. / Möglichkeiten der Schmerzverringerung durch Odemprophylaxe und Ausschaltung körpereigener schmerzerzeugender Substanzen.

The contemporary view of the cause of pain in case of histological lesions is discussed, i.e. the mechanisms of the formation of local high-protein oedemas in connexion with disorders of lymphatic drainage. 295 patients of an oral-surgical department were subjected to a systematic therapeutic study for investigating the possibilities of medicamentously influencing oedema and pain. Tested by way of comparison were a benzopyrone preparation (Venalot) and oxyphenbutazone. A group of control patients could only make use of an analgetic. The assessment of the reduction of oedema was done by means of anthropometric measurements. The analgetic action was judged by the need of analgetics. The result of it was that the benzopyrone preparation possesses a strong analgetic and antioedematous action which also exceeds that of the comparative therapy. The benzopyrones' clinical mechanisms of action are discussed in the light of experimental results.

Tanderil/chloramphenicol eye ointment in the treatment of the "Red Eye" seen in general practice.

An open study is reported in which 35 general practitioners treated 128 patients suffering from 'Red Eye' with a new eye ointment containing 10% Tanderil(oxyphenbutazone) and 1% chloramphenicol. One hundred and seventeen patients completed the seven day treatment period, in which time 99 had completed resolution of the symptoms and were discharged, the remaining 18 patients needed a longer period of treatment. Eleven patients failed to complete the study period, of whom 5 patients were subsequently referred to a specialist and 6 had their treatment changed by the general practitioner. Six patients showed signs of allergy to the ointment, all of whom were being treated for allergic conjunctivitis. Seventeen per cent of patients had some difficulty in applying the eye ointment or complained of subsequent blurring of vision.

Anti-inflammatory and antiproteolytic properties of 2-[acyl-N-(substituted benzylidene)hydrazino]5-phenyltetrazoles.

Ten 2-[acyl-N-(substituted benzylidene)hydrazino]5-phenyltetrazoles were synthesized, characterized and evaluated for anti-inflammatory and antiproteolytic activity. The protection afforded by these tetrazoles at a dose of 100 mg/kg i.p., against carrageenin-induced edema in rats, ranged from 11 to 46%. Oxyphenbutazone (40 mg/kg i.p.), and hydrocortisone (10 mg/kg i.p.), used as reference drugs, exhibited protection of 54 and 47%, respectively. The antiproteolytic activity of these tetrazoles, as reflected by their ability to inhibit trypsin-induced hydrolysis of bovine serum albumin, ranged from 17 to 57%. The antiproteolytic activity was found to be unrelated to the anti-inflammatory activity possessed by these tetrazoles.

Protection of carrageenin edema and trypsin hydrolysis of bovine serum albumin by naphthylthiosemicarbazides and their cyclized oxadiazoles.

Seven 1-(naphth-1-ylacetyl)-4-substituted thiosemicarbazides were synthesized and cyclized to the corresponding 2-(naphth-1-ylmethyl)-5-arylamino-1,3,4-oxadiazoles. All compounds, with the exception of two slbstituted oxadiazoles, possessed low anti-inflammatory activity. The protection afforded by these compounds against carrageen-in-induced edema ranged from 3 to 43% where cyclization, in general, decreased anti-inflammatory activity. All compounds (1 mM), possessed antiproteolytic activity where in vitro protection of trypsin-induced hydrolysis of bovine serum albumin, in most cases was greater with oxadiazoles.