Meta-analysis of hydroxyethylrutosides in the treatment of chronic venous insufficiency.

The efficacy of O-(beta-hydroxyethyl)-rutosides (HR) in chronic venous insufficiency (CVI) was assessed by using a meta-analysis on the basis of randomized trials. Analyzed parameters were clinical symptoms related to CVI, i.e. pain of the legs, nocturnal cramps, tired legs, swelling sensations and restless legs. The treatments had to be administered for at least 4 weeks and the average HR dose chosen was 1000 mg/day. On a total of 21 evaluated trials, 15 were selected that included 1973 patients. The placebo-treated group showed a significant (p < 0.01) improvement of patients (i.e., disappearance of the symptoms) as follows: pain 27%, cramps 26%, tired legs 22%, swelling 35% and restless legs 26%. Compared to placebo, the mean additional improvement in favour of HR was 11% for pains, 12% for cramps, 12% for restless legs, 14% for swelling and 24% for tired legs. All these improvements were significant (p < 0.01). The results were robust and stood up to the treatment effect to all meta-analyses across subgroups of randomized clinical trials. In conclusion, this meta-analysis shows that, despite the high response rate to placebo therapy, the effect of HR therapy is significantly superior in the treatment of symptoms related to CVI.

Lack of endocrine systemic side effects after topical application of spironolactone in man.

In six healthy male volunteers, the percutaneous absorption of spironolactone was compared with placebo in a double-blind crossover study. The subjects were randomly given either a cream containing 5% spironolactone or placebo to be applied in a randomized sequential way to a well defined skin area equivalent to 55% of body area. During the 72 h following the application of the ointment, blood levels of canrenone, the major metabolite of spironolactone, have been determined. In order to estimate the systemic antiandrogenic effect of spironolactone, plasma levels of 17-alpha-Hydroxy progesterone (17 alpha-OH-P), Testosterone (pT) and non-conjugated 3 alpha-Androstanediol (3 alpha-diol, metabolite of the active androgen 5 alpha-Dihydrotestosterone or DHT) as well as salivary Testosterone (sT) which relate to the free and active plasma testosterone fraction have also been measured. Urinary levels of canrenone have been determined 48 hours after cream application. No changes in any levels of these hormones have been detected and plasma canrenone levels were undetectable during the 72 hours of topical treatment. Topically administered, spironolactone appears to have only a local skin impregnation.

The effect of the alkaloid (-)cathinone on the motor activity in mice.

Khat leaves, widely used as a stimulant in East Africa and the Arab Peninsula, contain the alkaloid, (-)cathinone. This substance was found to cause in mice an increase of locomotor activity characterized by a dose-effect relationship typical for amphetamine. Furthermore, the effect of (-)cathinone was inhibited by pretreatment of the animals with the neuroleptics haloperidol, spiroperidol, pimozide, flupentixol and butaclamol. Pretreatment with reserpine reduced the effect of (-)cathinone moderately; in reserpinized mice the effect of (-)cathinone was antagonized by the uptake inhibitors mazindol and nomifensine. Together, these observations indicate that the pharmacology of (-)cathinone hypermotility closely parallels that of amphetamine hypermotility. The results suggest that the stimulating properties of khat leaves are due to the presence of an alkaloid with amphetamine-like effects.