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The aim of this study was to use the Zurich polyspecies biofilm model to compare the antimicrobial effects of chlorhexidine mouth rinses available on the Swiss market. As positive and negative controls, aqueous 0.15% CHX solution and water were used, respectively. In addition, Listerine® without CHX was tested. Biofilms in batch culture were grown in 24- well polystyrene tissue culture plates on hydroxyapatite discs in 70% mixed (1:1 diluted) unstimulated saliva and 30% complex culture medium. During the 64.5-hour culturing period, the biofilms were exposed to the test solutions for 1 minute twice a day on two subsequent days. Thereafter, the biofilms were dip-washed 3 times in physiological NaCl. Following the last exposure, the incubation of biofilms was continued for another 16 h. They were then harvested at 64.5 h. The dispersed biofilms were plated on 2 agar media. After incubation, colonies (CFU) were counted. All solutions containing CHX as well as Listerine ® significantly reduced the number of microorganisms in biofilms. According to their efficacy, the mouth rinses were classified into 2 groups. The two Curasept ADS solutions, Parodentosan, and the Listerine® mouth rinse reduced the number of total CFU by 3 log10 steps. This seems sufficient for a long-lasting prophylactic application. The two PlakOut® mouth rinses and the CHX control fell into the other group, where the number of CFU was reduced by 7 log10 steps. These mouth rinses are predestined for short-term therapeutic use. However, reversible side effects must be taken into account. It has thus far not been possible to formulate CHX products with effective ADS (Anti Discoloration System) additives without reducing antimicrobial activity.

Searching for more potent 5-lipoxygenase (LO) inhibitors one tert-butyl group of the selective 5-LO-inhibitor 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-hydroxy-1,4-naphthoquinone (1) was substituted by polar functions (-CHO, -COOH, -CH=CH-COOR, -CH2-CH2-COOR). At the same time the 5-LO selectivity of the new compounds within the arachidonic acid cascade was investigated. For this 12-LO- and COX-1-assays with activated human platelets were used. Screening the test compounds new selective 5-LO-inhibitors (4, 9 and 16) and a COX-1-inhibitor (10) as well as dual 5-LO/COX-1- (23) and 12-LO/COX-1- (12) inhibiting compounds were found. Obviously in this class of compounds 5-LO and 12-LO inhibition are mutually excluded for a structural reason. In addition to the well known 3-chloro- (19) and 3-bromo- (20) analogues of 1 the 3-fluoro- (22), 3-iodo- (23) and the 3-carbonitrile- (24) derivatives were synthesized. All 3-halogen compounds, except 23 and the nitrile, are potent non selective inhibitors of all three enzymes. Causative for this unselectivity is the inhibition of the arachidonic acid release by inhibition of the cytosolic phospholipase A2 (cPLA2) with the exception of 24.

Three radioactively marked substances (on the basis of a carbopol gel, 80% water - isopropanol) were analyzed comparatively in regard to the penetration of ethyleneglycolmonosalicylate and benzylnicotinate to intact and impaired human skin. The objective of the in-vitro study was to gain evidence on possible interaction of the locally applied substances upon skin penetration. Only 5 h after application ethyleneglycolmonosalicylate reaches a steady state of concentration in the corium of approximately 700-800 mumol/l tissue which is maintained (in contrast to nicotinate) even after 16 h exposure time. Benzylnicotinate reaches its maximum concentration (100-200 mumol/l tissue in all living layers of the skin) 100-300 min after application. After simultaneous local application of both substances the penetration of ethyleneglycolmonosalicylate in corium and subcutis is clearly intensified by benzylnicotinate. Substance distribution in skin cross section and kinetics do not change. Penetration of benzylnicotinate however, is delayed by the salicylate (especially at exposure time of 100-300 min). Results of comparative penetration studies with inverted skin (inverse penetration), intact and impaired (stripped) skin allow the following conclusion: penetration limiting of salicylate occurs in the horny layer only due to the optimal liberation. Penetration of nicotinate on the other hand, is already prevented "before" the skin because of insufficient liberation from the vehicle.

Valproic acid has become a regular component of antiepileptic therapy. Generally it is used against genetically caused, primary generalized epilepsies with bilateral hypersynchronous neuronal discharges in the EEG. An improvement can also be observed by Valproic acid-treatment for secondary generalized and partial epilepsies. Therapeutic results could possibly be improved through a consideration of the serum concentration of valproic acid. Some of the commercial preparations contain the sodium salt of Valproic acid. The free acid which is quickly absorbed, is released in the stomach (tablet) or in the intestine (dragee). The half life is about 15 to 17 hours (one finds a range of 6 to 20 hours in the literature). In view of the half life, it is recommended that the daily dose should be divided into three single doses. About 84 to 95% of the substance is protein bound. Up to now, clinically relevant observations concerning the displacement of valproic acid from its protein binding are unknown. Recently in in vitro studies a decreased protein binding of valproic acid due to phenylbutazone, salicylic acid, and sulfadimethoxine and vice versa, a displacement of phenobarbital and phenytoin caused by valproic acid could be demonstrated. The therapeutic range of the serum level was between 50 and 120 mcg/ml. Individual patients showed that the dispensed dose did not reliably yield the expected serum levels. The necessary daily dose lies for adults between 600 and 2400 mg, in children between 15 and 150 mg/kg. The wide range of allowable dosis is dependent on whether or not valproic acid is to be given in conjunction with other antiepileptic drugs. When phenobarbital and valproic acid are given in conjunction one should be alert for a rise in the phenobarbital serum level. Results of studies in which valproic acid was combined with several other antiepileptic and psychotropic drugs are reported. The majority of the researchers determine a clear parallelism between clinical improvement and a normalization of the EEG in primary generalized epilepsies with bilateral synchronous 3/sec. spikes and waves. The background activity, determined by visual inspection, is not affected. Few workers discuss the correlation of the side effects of valproic acid and its serum level. Tiredness and impaired function of thrombocytes has been observed to be dependent on the valproic acid plasma level.

The synthesis of 5-bromosalicyl-4'-chloroanilide-O-beta-D-xylopyranoside and other glycosides of 5-bromosalicyl-4'-chloroanilide, salicylanilide, 3,5-dichlorophenol and tetrachlorohydrochinone is described. Glycosidations follow the procedures described by Latham et al. Sabalitschka and Helferich et al. These glycosides represent relatively untoxic transport-forms of drugs, which are activated to the free drug by specific enzymes of the organisms to be destroyed. This new mechanisms can help to destroy fungi and parasites in dermatology, agriculture, horticulture and cultivation of decorative plants without side effects on the host.

Acetylsalicylic acid inhibits platelet function. In plasma acetylsalicylic acid is rapidly deacetylated to salicylic acid which is slowly eliminated and has no direct inhibitory effects on platelet function. However, salicylic acid prevents the inhibition by acetylsalicylic acid of collagen-induced aggregation of human thrombocytes in vitro. It was suggested that salicylic acid might inhibit the antiplatelet effects of acetylsalicylic acid in vivo and therefore low-dose acetylsalicylic acid would be more effective for antithrombotic therapy. A 500-mg tablet of acetylsalicylic acid applied 90 min after oral administration of 500 mg salicylic acid to six healthy male volunteers led to the same inhibition of collagen-induced platelet aggregation and tissue-extract-induced platelet stimulation as 500 mg acetylsalicylic acid alone. These results cannot give additional support to the recommendation of low-dose acetylsalicylic acid in the prevention of thromboembolic disease.

Test results are reported of the effect of salicylic acid on the vasoconstrictive effect of flumethasone pivalate. In specific, the depigmentation of the skin (identical with increase in lightness of the skin) following topical application of flumethasone pivalate was investigated with the aid of an improved spectrophotometric method. Using numeric lightness evaluation it was possible to demonstrate that salicylic acid increases the vasoconstriction.

Salicylic acid in the therapeutic concentrations from 0.5 to 10% does not affect the rate of proliferation of psoriatic epidermal cells. In 18 patients suffering from psoriasis the H3-I (H3-thymidine labelling index) was determined using autoradiographic in vitro labelling techniques. In 12 of these patients double-labelling with C14-and H3-thymidine was used to determine the H3-I, the DNA-synthesis time (ts) and the duration of the cell-cycle (tc). No significant changes were observed following external application of salicyclic acid in white Vaseline in concentrations of 0.5, 2 and 10% for one week.

Investigation on 60 volunteers are reported in whom the influence of salicylic acid and finely divided sulfur on the blanching effect of ointments with and without steroid was analysed. The higher the concentration of salicylic acid the greater is the decrease in the blanching effect of the steroid free ointment. At low concentrations finely divided sulfur also reduces the blanching effect of the steroid is reduced by salicylic acid as well as by sulfur. This effect is at least partly produced by the decrease of the blanching effect due to the base. An increase in the bioavailability of corticosteroids in the skin after local application cannot be achieved by addition of salicylic acid or sulfur under the conditions chosen.

Five contact antiphlogistics were evaluated and compared to hydrocortisone by the human skin vasoconstriction assay in 20 volunteers. The test concentrations ranged from 10(-2) to 10(-6) w/w; the duration of occlusive application was 16 h. The substances could be ranked as follows in ascending order of activity (index values in relation to hydrocortisone).

The right lower inner arms of 22 healthy test persons in total have been treated either with 6% salicylic acid solution in 70% isopropyl alcohol, or with 5% precipitated sulphur mixture in white petrolatum, or with a surfactant mixture. The basic preparations without active agents have been applied to the corresponding skin area on the left arms. The thickness of the corneal layer on both arms was measured by means of the cantharidin blister method. Salicylic acid, sulphur, as well as the surfactant mixture all led to a more significant reduction of the corneal layer than the basic preparations. Under the chosen test conditions, the keratolytic effect of all three substances has thus been proven.

Bismuth salts are successfully used for the treatment of campylobacter-pylori-associated gastritis. It cannot be excluded, however, that calcium carbonate, which is present in one of the recommended preparations (calcium carbonate/bismuth subsalicylate, Jatrox), may have an additional therapeutic effect due to an increase of intragastric pH. Therefore, the in-vitro H+ buffering capacity of Jatrox was determined in comparison to other antacids using the pH-stat technique, and its effect on intragastric acidity was tested in 15 healthy volunteers using ambulatory 24-hour pH-metry (combined glass electrode in gastric corpus, solid state memory recorder, sampling rate 30/min). At two study sessions, the volunteers received standardized normal meals (8:00 a.m., 12:00 noon, 6:00 p.m.) and, in randomized order, either Jatrox (three times 2 tablets one hour before meals) or no medication. Under in-vitro conditions, the buffering capacity of Jatrox amounts to 7.82 mmol H+ per tablet (equivalent to 47 mmol H+/24 h at recommended dosage), which is relatively low. Under in-vivo conditions, gastric pH only increases significantly during the first hour after medication. This short-lasting effect, however, has no influence on the 24-hour median pH. It is concluded from these results that the calcium carbonate contained in Jatrox probably does not contribute directly towards its therapeutic effect in promoting the healing of gastritis.

The influence of the hexylsalicylic acid (2) on the pharmacokinetic of the quinine (1), was studied using rabbits. It could be observed that after i.v. application the mean resistance time (MRT) of 1 was increased by means of ion-pair-formation with 2. But the AUC of 1 was not influenced. After rectal application of the combination 1/2 an acceleration of the 1 absorption could be pointed out. The kinetic parameters of 2 were not increased significantly if 1 was applicated simultaneously.

Six different soft lens solution have been tested to investigate their effect on the healing process of a corneal erosion, experimentally scratched in rabbit-cornea. Healing delays have been observed in every cases; also by three medicaments which are used for "dry" eyes. The latter ones should never have a conjunctival application. Theexplanation of those healing delays is given by the concentration properties of HEMA-lenses for disinfectants. The admixtures of soft lens solutions like buffers and liquid polymerscause and additive effect on retardment of coeneal regeneration.

A cholinesterase deriving from the hemolymph of the mussel Mytilus edulis was partially purified by use of gel-permeation and ion-exchange chromatography; the specifity to different substrates or inhibitors indicates clearly the occurrence of a "true" acetylcholinesterase.

Side effects of non-steroidal antirheumatic drugs (NSAD) may occur in any organ system, since the prostaglandins, the synthesis of which is inhibited by NSAD, play a role in numerous adverse cellular processes throughout the body. Besides these physiologic regulations there are adverse effects of NSAD, such as bone marrow aplasia, of unexplained etiology. The interactions of NSAD are of clinical relevance in drug types such as the salicylates, pyrazolons and fenamic acids (e.g. interactions with cumarin derivatives). The clinically relevant interactions of NSAD are discussed in detail.

The authors present a choline salicylate gel at present on trial and compare it, by means of microbiologic studies, with Grisaldon as to composition, consistency and bacteriostatic properties. Choline salicylate showed a good bacteriostatic effect. As to Grisaldon, the conditions are considerably less favorable due to the poor solubility of acetylsalicylic acid.

The mode of action of "classical peeling agents" such as resorcinol, crystalline sulfur, and salicylic acid on the epidermis is almost unknown. There are only a few experimental data available. Therefore the effects of resorcinol, crystalline sulfur, and salicylic acid were studied. A 1% and 3% concentration of these chemicals in vaselinum flavum or Unguentum Cordes was applied to the ears and flanks of adult male guinea pigs up to 14 days. Prior to biopsies at various time intervals, 3H-thymidine was injected intradermally. Specimens were paraffin embedded and routinely processed for autoradiographical analysis. The following parameters were assessed: Labelling index (L.I. in %); number of labelled basal cells per unit length of basement membrane; papillomatosis-index; and acanthosis-factor (projection histoplanimetry). The data were statistically analysed. The peeling agents induced a concentration-dependent increase of the L.I., acanthosis, and papillomatosis. Crystalline sulfur caused the most pronounced effect, followed by resorcinol. In contrast salicylic acid caused only a minute acanthosis factor and a slight increase in labelling. The correlation coefficient r of epidermal thickness to the L.I. for all concentrations and peeling agents used reaches the high figure of 0.978 for the ear. The 1% and 3% salicylic acid has a lower acanthosis factor than vaselinum flavum by itself. Preliminary autoradiographical studies in humans with 1% and 10% salicylic acid confirm these data. Salicylic acid counteracts acanthosis. These experiments show that crystalline sulfur and resorcinol have a potent effect on cell proliferation and acanthosis. They peel via proliferation hyperkeratosis. The mode of peeling by salicylic acid must be different, as cell proliferation and acanthosis are barely enhanced. The clinically known "keratolytic" effect of salicylic acid may be due to a direct action on the intercellular cement substance of the horny cells.

The effects of an 8-week treatment with the quinine-lithium-salicylate combination Togal and sole acetylsalicylic acid (ASA) on the hemopoietic bone marrow cells of mice were studied. In general, both substances caused only minor changes. A slight leukopenia caused by higher doses as well as a transitory erythropenia observed a little bit more distinctly in ASA treated animals than in Togal treated animals need more detailed discussion, especially so because after a short two-week Togal treatment some animals showed an increase of hemopoietic cell colonies which a sole ASA dose did not cause. On the other hand, these results indicate a lower toxicity of Togal in comparison with acetylsalicylic acid as has been already shown in several other publications. It was proven that after a several weeks' treatment with therapeutic doses no pernicious influence on blood producing organs or pathological processes of the blood picture occurred. Only doses that border on the toxic region lead to insignificant bone marrow changes. As these over-doses are ten times the highest therapeutical dose the use of Togal does any damage to the blood forming tissue or pathological changes in the blood count are not likely. This has also been proved by other authors by means of long-term tests on humans.