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Superficial thrombophlebitis is a frequently occurring disease which, because of risk factors, affects women to a greater extent than men. The presence of deep venous thrombosis should be excluded by imaging procedures. Heparin or low-molecular weight heparins are indicated for treatment, if deep venous thrombosis is present or threatening. In the acute stage non-steroidal antiinflammatory drugs can be taken orally in order to alleviate pain and inflammation. In the case of concomitant chronic venous insufficiency, edema protective drugs (e. g. preparations containing horse chestnut extract and flavonoids) can support the therapy. For the treatment of inflammatory conditions in relatively short superficial vein segments without involvement of the deep venous system, a limitation to topical treatment is possible. In addition to compression therapy, the application of creams or gels containing heparin or heparinoids are the usual treatment approach. The use of topical products containing mucopolysaccharide polysulfate (MPS) has been proven to be beneficial. The problem of providing evidence of the efficacy of topical products in the therapy for superficial thrombophlebitis under the current strict demands of our regulatory authorities and of developing new products under these conditions is discussed.

The cutaneous penetration of mucopolysaccharide polysulfate (MPS) from a commercial available combination drug (Mobilat) could be shown by means of histochemical and immunohistological methods. Deposition of MPS from ointment and gel in corium and subcutis of different animal species has been improved by the keratolytic activity of the salicylic acid component. There are differences in the intensity of absorption of MPS not only in the various animal species, but also caused by the particular galenic preparations investigated.

1. Phagocytic activity measured by means of the intravasal clearance of a soot dispersion in male NMRI-mice was increased six to ten days after whole-body X-irradiation (640 R) and decreased during the same period after i.v. administration of 2,4,6-triethyleneimino-s-triazine (TEM 2.0 mg/kg). 2. By means of 6-methyl-uracil food admixtures (200 to 400 ppm during 2 or 3 weeks) or by repeated intravenous injections of a N-methyl-D-glucosamine-6-methyluracil complex (62.5 to 250 mg/kg daily during five days), a significant augmentation of the phagocytic index being related to time and dosage was obtained in otherwise untreated mice. Comparable results were seen using cytidine and cytidine-s'-phosphate, whereas guanosine-5'-phosphate remained ineffective. 3. Whilst stimulating effects of 6-methyl-uracil or its N-methyl-D-glucosamine complex on X-irradiated mice were suspended, an increase up to supernormal values of the phagocytic index was produced by the pyrimidine base in animals treated with TEM. In accordance to this the survival rate of lethally X-irradiated mice (960 R) could not be increased; with animals given lethal TEM-doses, however, a significantly increased survival rate was obtained. 4. The present investigations as well as former biochemical analyses confirm the assumption that 6-methyluracil produces its regeneration effects, to some extent at least, by specific pathways influencing the reticuloendothelium. Different results from X-irradiated and TEM-treated mice are referring to the different points of attack of the two noxa.

The in vitro incorporation of 14C-thymidine into DNA of bone-marrow cells as well as DNA content of spleen and thymus of male Wistar rats were increased significantly by 6-methyluracil (within an N-methyl-D-glucosamine-6-methyluracil complex) and/or heterologous, low-molecular nucleic acids, when given therapeutically at doses of 100--250 mg/kg b.w. following i.v. injection of tretamine. Maximum effects were reached as early as two days after the onset of experiment. When tretamine was replaced by X-irradiation or cyclophosphamide, the influence of the 6-methyluracil complex and nucleic acids was less significant. Whereas normal bone-marrow cells and cells damaged in vitro by X-irradiation, tretamine and/or inhibitors of protein synthesis could not be influenced by the 6-methyluracil complex, incorporation of 14C-L-phenylalanine into proteins of bone-marrow cells was enhanced by exogenous DNA or RNA (10--100 micrograms/ml). The present investigations underline the previously drawn conclusions that certain biological alkylating agents, nucleic acids and pyrimidines may interfere to some extent through the reticuloendothelial system.

Survival time of mice after i.v. injections of 2,4.6-triethylene-imino-1,3,5-trazine (TEM) or total body-X-irradiation (TBI) was increased by 6-methyluraclil (6-MU) when given in food (200 ppm). Under the same conditions, 6-MU decreased the involution of spleen and thymus (as measured by DNA-content and DNase II activity) under the infuence of TEM and enhanced the regeneration of the spleen after TBI. Elevation of DNase I- and protein content of the kidneys and a (short-dated) increase of incorporation of 14C-phenylalamine into microsomes of liver of 14C-orotic acid into RNA of liver and kidney suggest that the influence of 6-MU is mediated at least partly by a specfically anabolic effect.

It could be demonstrated by means of the UV erythema model that four different ointment preparations containing mucopolysaccharide polysulfate (MPS) have a marked antiinflammatory effect and inhibit the formation of erythemas to a large extent. In this trial arrangement the different preparations containing MPS were significantly superior to altogether eight commercial heparin ointments, which were tested, too. With an inhibition of 69% of the erythema induced by UV rays, Hirudoid 40000 ointment is the most effective of all preparations tested.

The anti-exudative and anti-edematous effects and the dose-effect relationship of a-sympathomimetics, especially of l-phenylephrine-HCl (PE), have been demonstrated using as model the rat pad-carrageenan edema and the histamine liberator test, the dosage being administered cutaneously, orally, and intraperitoneally. The beta-receptor activating compound bamethane sulfate was not effective when used on the same models. Evidence of percutaneous penetration of PE was provided both on isolated skin and in viro. PE, when injected intravenously or subcutaneously, produced a rise of blood pressure in experimental animals. When PE was administered orally and cutaneously, it did not, however, alter the blood pressure. The anti-inflammatory and anti-exudative effects remianed unchanged.