Parenteral troxerutin and carbazochrome combination in the treatment of post-hemorrhoidectomy status: a randomized, double-blind, placebo-controlled, phase IV study.

Flavonoids, such as troxerutin, have been shown to be safe and effective agents for the treatment of chronic venous insufficiency. The fixed combination between troxerutin 150 mg and carbazochrome 1.5 mg (Fleboside ampoules) was previously shown to have a good efficacy and safety profile in non-surgical patients with acute uncomplicated hemorrhoids. The purpose of this randomized, double-blind, placebo-controlled study was to investigate the efficacy and tolerability of the active combination in the treatment of post-hemorrhoidectomy patients. 30 patients were randomized to receive one of two treatments: troxerutin 150 mg and carbazochrome 1.5 mg, or placebo, i.m. 3 ml ampoules twice a day for five consecutive days after the surgical procedure, starting from the day of surgery. Efficacy parameters were assessed as follows: at baseline (T1), after the first administration (T2; day of surgery), the second day after the surgical procedure (T3), and the fifth day after the surgical procedure (T4); hemorrhoidal symptoms based on a visual analogue scale (VAS): pain, discharge, bleeding, inflammation, and pruritus; analgesic intake, if any; time to restore a physiological defecation; edema evaluation (based on a four-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe); camera pictures taken at T1 and T4 (in selected patients); and blood coagulation tests. Analysis between treatment groups revealed a highly significant difference at T3 and T4 for the total VAS score (p = 0.007 and p = 0.001, respectively) in favor of the active combination treatment. A statistically significant difference was also observed for bleeding and pruritus at T3 and for these two parameters and both inflammation and edema at T4 (p < 0.001) in favor of the active combination group. No adverse events were reported. Neither the active combination nor placebo affected blood coagulation tests. We conclude that intramuscular administration of the fixed combination of troxerutin 150 mg and carbazochrome 1.5 mg is effective, well tolerated and superior to placebo in improving hemorrhoidal and post-surgical symptoms during the five days following surgery.

Effect of bioflavonoids (trihydroxyethylrutin and disodium flavodate) in vitro on neutrophil reactive oxygen production and phagocytic ability assessed by flow cytometry.

Neutrophil granulocytes have been described as agents of defence and destruction. The effect of two flavonoid compounds (trihydroxyethylrutin and disodium flavodate) on the phagocytic ability and generation of reactive oxygen radicals of neutrophils was studied at concentrations of 5 mg/l, 50 mg/l and 100 mg/l. Flow cytometry was used to study phagocytic ability by measuring uptake of fluorescein-labelled bacteria. The generation of reactive oxygen intermediates was estimated by means of a CD16 phycoerythrin-conjugated mouse anti-human monoclonal antibody. In vitro trihydroxyethylrutin (THET) and disodium flavodate (DF) treatment reduced reactive oxygen production (DF at 5 mg/l--40%, at 50 mg/l--71% and at 100 mg/l--82%; THET at 5 mg/l--53%, at 50 mg/l--88%, at 100 mg/l--93%; all p < 0.001). This was rapidly reversible after plasma exchange. Both flavonolds did not affect neutrophil phagocytic ability. We conclude that THET and DF could decrease oxidative tissue damage by neutrophils. A beneficial effect in peripheral vein disease could be anticipated from these results.

Treatment of venous leg ulcers with 5% amikacin gel: phase IV trial.

A phase IV trial with 5% amikacin gel was carried out on 100 adult in patients of both sexes suffering from venous infected leg ulcers. After 2 weeks' therapy the microbiological culture tests were negative for more than 80% of the patients. The mean ulcer surface area was reduced by 34% and the accompanying symptoms of erythema, inflammation and pain were improved. Only very mild unwanted local effects were reported by four out of the 100 patients. Five percent amikacin gel was judged a safe and effective topical treatment for curing infected venous leg ulcers.

Oral and intravenous pharmacokinetic profiles of doxofylline in patients with chronic bronchitis.

Serum doxofylline concentrations were evaluated after solid-phase extraction by high-performance liquid chromatography following administration of 100 mg doxofylline given as a single intravenous dose over 10 min or 400 mg doxofylline given orally twice daily for 5 days in six and eight non-smoking, fasting, chronic bronchitic patients, respectively. Doxofylline possessed a very short distribution phase following intravenous administration, with a sustained elimination phase (half-life 1.83 +/- 0.37 h). After oral administration, the peak serum doxofylline concentration was 15.21 +/- 1.73 micrograms/ml and the mean elimination half-life was 7.01 +/- 0.80 h; there was a large inter-subject variability. No side-effects were experienced by the patients during the study.

[Physiopathology and therapy of female idiopathic hirsutism. State of the art]. / Fisiopatologia e terapia dell'irsutismo idiopatico femminile. Lo stato dell'arte.

This review aims at focusing current pathogenetic theories on female idiopathic hirsutism. Glandular hormonal synthesis, plasma transport of androgenic hormones, and cutaneous metabolism and utilization of testosterone are discussed in detail. The Authors then propose some therapeutic strategies: antiandrogen drugs are discussed with special reference to cyproterone acetate and spironolactone.

Doxofylline exerts a prophylactic effect against bronchoconstriction and pleurisy induced by PAF.

The effect of doxofylline, a new xanthine drug with a low incidence of side-effects in the central nervous, renal and gastroenteric system, on the actions of PAF-acether on bronchopulmonary functions was studied. Doxofylline inhibited: (1) PAF-induced bronchoconstriction in vitro, and the concomitant generation of TXA2-like activity in perfused guinea-pig lungs; (2) PAF-induced bronchoconstriction in vivo and the concomitant release of TXA2-like activity into the circulation; (3) PAF-acether-induced pleurisy and the liberation of type C4 leukotriene into the rat pleural cavity. The results suggest that doxofylline, like theophylline, is able to counteract the bronchoconstriction induced by PAF-acether and, in addition, displays anti-inflammatory properties. These pharmacological data support the notion that doxofylline exerts a prophylactic effect against the respiratory damage induced by mediators, such as PAF-acether, of lung bronchial hyperreactivity; its mechanism of action is unusual, it has slight antagonistic activity at A1- and A2-adenosine receptors.

Antiandrogens and hirsutism.

The clinical appearance of female idiopathic hirsutism and its pathophysiological aspects and the antiandrogen drugs in relation to the therapy of hirsutism are discussed. Two compounds have been widely employed, namely cyproterone acetate, mainly in the 'reverse sequential regimen', and spironolactone, with or without the association of a contraceptive pill containing cyproterone acetate and ethinylestradiol. The ability to compete with dihydrotestosterone in skin androgen receptors, shared by these two compounds, has led to excellent clinical results for many years. A topical antiandrogen therapy would be a further advantage for these patients.

Platelet-activating factor--a powerful lipid autacoid possibly involved in microangiopathy.

Microvascular injury includes diffuse endothelial and periendothelial damage and increased leukocyte/platelet-endothelium interactions including cell adhesion and liberation of powerful autacoids, growth and coagulation factors, all capable of causing vessel wall injury. Platelet-activating factor (PAF) is an ether-lipid mediator of inflammation, produced by and active on both platelets and endothelial cells (EC) at nanomolar concentrations. Its structure, biosynthesis and origin as well as some regulatory properties of the related enzymes are considered. The in vivo effects of PAF, as well as its action on selected cell types, such as platelets, neutrophils and EC, are briefly reviewed. PAF production may explain the intervention of platelets and neutrophils as well as increased vascular permeability in kidney, lung and retinal diseases. Pharmacological modulation of PAF production and activity is discussed with particular attention to the inhibitory effect of calcium dobesilate, a drug used in human diabetic retinopathy, on PAF production from the human endothelial cell line EA926.

Comparison between adrenal steroid secretion after stimulation with two synthetic analogues of corticotropin : ACTH 1-24 and ACTH 1-17.

Chemical manipulations of the native ACTH (1-39) molecule led to the synthesis of a newly characterized compound which shows several interesting features, such as an enhanced half-life, an increased resistance against enzymic degradation and lower immunogenic activity. This study aimed at comparing the adrenal steroidogenetic response of the 1-17 analogue and of the other commercially available synthetic ACTH (1-24). Results suggest that ACTH 1-17 has a more pronounced and prolonged activity, which is confined to glico- and mineralocorticoid secretion.

[Intracellular and extracellular proteins binding androgenic hormones. Biochemical properties and clinical significance]. / Le proteine intracellulari ed extracellulari leganti gli ormoni androgeni. Proprietà biochimiche e rilevanza clinica.

This paper has been designed to review some current concepts about biochemistry, pathophysiology and clinics of androgen-binding proteins, both TeBG and cellular receptors. Some important experimental models to clarify the interactions between androgens and target cells are mentioned. Further, major clinical applications in which binding parameters were or will be of great importance are discussed in details.

Antiandrogenic properties of spironolactone. Clinical trial in the management of female hirsutism.

The effect of spironolactone on female hirsutism was studied in 18 patients. The drug was administered at the dose of 400 mg for the first ten days and 300-200 mg later on in a first group of women (Group A); a second group (Group B) was given 200 mg spironolactone for the whole length of therapy. A significant decrease of the index of Ferriman and Gallwey (p = 0.01) was noted from the 100th day of treatment; acne and seborrhoea improved concomitantly. Plasma total testosterone values fell from 0.64 +/- 0.24 ng/ml to 0.32 +/- 0.12 ng/ml (p = 0.002) during the first 5 days only in the patients of Group A; in the other patients no significant changes were observed. PRL did not significantly change from pretreatment values; FSH and LH values at the 5th, 10th, and 15th day of therapy did not show a uniform course in both groups. On the basis of these results spironolactone administration appears promising in the therapy of female hirsutism.