Nasal powders of thalidomide for local treatment of nose bleeding in persons affected by hereditary hemorrhagic telangiectasia.

In this work nasal powder formulations of thalidomide were designed and studied to be used by persons affected by hereditary hemorrhagic telangiectasia as a complementary anti-epistaxis therapy, with the goal of sustaining the effect obtained with thalidomide oral treatment after its discontinuation for adverse effects. Three nasal powders were prepared using as carriers ß-CD or its more hydrophilic derivatives such as hydropropyl-ß-CD and sulphobutylether-ß-CD and tested with respect to technological and biopharmaceutical features after emission with active and passive nasal powder devices. For all formulated powders, improved dissolution rate was found compared to that of the raw material, making thalidomide promptly available in the nasal environment at a concentration favouring an accumulation in the mucosa. The very limited transmucosal transport measured in vitro suggests a low likelihood of significant systemic absorption. The topical action on bleeding could benefit from the poor absorption and from the fact that about 2-3% of the thalidomide applied on the nasal mucosa was accumulated within the tissue, particularly with the ß-CD nasal powder.

Ex vivo permeation of tamoxifen and its 4-OH metabolite through rat intestine from lecithin/chitosan nanoparticles.

Tamoxifen citrate is an anticancer drug slightly soluble in water. Administered orally, it shows great intra- and inter-patient variations in bioavailability. We developed a nanoformulation based on phospholipid and chitosan able to efficiently load tamoxifen and showing an enzyme triggered release. In this work the permeation of tamoxifen released from lecithin/chitosan nanoparticles across excised rat intestinal wall mounted in an Ussing chamber was investigated. Compared to tamoxifen citrate suspension, the amount of the drug permeated using the nanoformulation was increased from 1.5 to 90 times, in absence or in presence of pancreatin or lipase, respectively. It was also evidenced the formation of an active metabolite of tamoxifen, 4-hydroxy tamoxifen, however, the amount of metabolite permeated remained roughly constant in all experiments. The effect of enzymes on intestinal permeation of tamoxifen was shown only when tamoxifen-loaded nanoparticles were in intimate contact with the mucosal surface. The encapsulation of tamoxifen in lecithin/chitosan nanoparticles improved the non-metabolized drug passing through the rat intestinal tissue via paracellular transport.

[Use of ursodeoxycholic acid combined with silymarin in the treatment of chronic ethyl-toxic hepatopathy]. / Impiego dell'acido ursodesossicolico associato alla silimarina nel trattamento della epatopatia cronica etiltossica.

30 patients, affected by chronic ethylic hepatopathy, were treated with 450 mg/daily of ursodeoxycholic acid (UDCA): after six months, a significant decrease of serum hepatic enzymes was noted. The addition of silymarin (400 mg/daily) to UDCA in other 30 patients, induced a further improvement of hepatic function.

Plasma and skin concentration of 5-methoxypsoralen in psoriatic patients after oral administration.

The aim of this work was to investigate the distribution of 5-methoxypsoralen in the skin after oral administration of the drug and to examine the correlation between skin and plasma concentrations. 5-Methoxypsoralen skin concentration was measured in both healthy and psoriatic sites of 10 psoriatic patients after single and multiple oral doses. The results obtained show that 5-methoxypsoralen accumulates at higher levels in the more external layers of the skin after oral administration. The high affinity of drug for the stratum corneum was confirmed by in vitro skin affinity measurements. The concentration of 5-methoxypsoralen in the skin was similar in both psoriatic and healthy sites, indicating that the pathology does not influence drug distribution in the skin. After single dose administration, a linear correlation was found between skin and plasma drug concentration. After multiple dose administration, drug concentration in the skin was fairly constant despite the variable plasma concentrations in different subjects.

[Electrophysiologic evaluation of athletes with Wolff-Parkinson-White syndrome: induction of supraventricular arrhythmia at rest and under exertion with transesophageal atrial electrostimulation]. / La valutazione elettrofisiologica degli atleti con Wolff-Parkinson-White: induzione di tachiaritmia sopraventricolare di base e sotto sforzo con elettrostimolazione atriale transesofagea.

The most suitable approach to the athletes with WPW is controversial. Therefore 66 symptom-free athletes with WPW and without heart disease (53 M, 13 F, mean age 21.98 yrs, min 12--max 44) underwent a study protocol whose end-point was the induction of supraventricular tachyarrhythmia, i.e. atrial fibrillation or, if not possible, atrial flutter or atrial tachycardia at rest and during ergometric stress test. The athletes with shortest R-R interval between preexcited beats less than or equal to 240 ms at rest and/or less than or equal to 210 ms during exercise were judged as being at risk i.e. no fit for sport activity. The end-point was reached in 64/66 athletes (in 62 atrial fibrillation). In 4 athletes with life threatening arrhythmia induced at rest the evaluation during exercise was not performed. According to the evaluation at rest we were able to identify only 18 athletes (28.1%) as being at risk, while according to the complete study protocol 26 athletes (40.6%) were judged as such. In 23/64 athletes (36%) this judgement was discordant with the usual non invasive evaluation (i.e. Holter monitoring, ergometric stress test, ajmaline test). During induced atrial fibrillation no significant difference, was found between the percentage of preexcited beats at rest and during exercise. On the average, 40 min. are required for performance of this study protocol (if the induced arrhythmia lasts less than 5 min.). According to our results we conclude: a) the non invasive assessment of the WPW athletes is unsatisfactory; b) the induction of atrial fibrillation during exercise gives a remarkable increase of the diagnostic power with respect to the assessment only at rest; c) since it is simple to perform and not expensive (in time, staff and cost) and because of its high diagnostic yield, we regard this protocol as fundamental for the electrophysiological evaluation of WPW athletes and also suitable for systematic study of WPW patients.

[Effects of amiodarone on atrio-ventricular and ventriculo-atrial conduction in the Wolff-Parkinson-White syndrome (author's transl)]. / Effetti dell'amiodarone sulla conduzione atrio-ventricolare e ventricolo-atriale nella sindrome di Wolff-Parkinson-White

In 10 patients with the Kent's bundle W.P.W. syndrome, the action of amiodarone (5 mg/kg i.v.) on conduction along the normal and anomalous pathways was studied. The drug actions were: 1) constant increase of the anomalous pathway E.R.P., in one case with antegrade functional block; 2) constant reduction of antegrade conduction velocity along the anomalous pathway, in one case with antegrade functional block; 3) reduction of retrograde conduction velocity along the anomalous pathway in 6 cases out of 8, including one with retrograde functional block; 4) constant increase of the A-V node E.R.P.; 5) reduction of sub Hisian A-V conduction velocity in 3 cases out of 7. Episodes of reciprocating tachycardia could be initiated by atrial electrostimulation in 5 patients before administration and in 3 following administration of the drug. In connection with the electrophysiological properties of the two atrio-ventricular pathways and on the mechanism of tachycardia, the use of this drug in prevention of the circus movement tachycardia in patients with the W.P.W. syndrome is discussed.