Improved tretinoin photostability in a topical nanomedicine replacing original liquid suspension with spray-dried powder with no loss of effectiveness.

OBJECTIVE: The use of spray-dried powders containing tretinoin-loaded nanocapsules instead of the original liquid suspension, aimed at the preparation of dermatological nanomedicines with improved photostability, was investigated. METHODS: Powders were prepared using lactose as a drying adjuvant. Hydrogels were prepared using two approaches: dispersing Carbopol Ultrez 10 in an aqueous redispersion of the powder or incorporating the powder in previously formed hydrogels. RESULTS AND DISCUSSION: The photodegradation of tretinoin in hydrogels prepared with the powders showed similar half-life times (around 19.5 h) compared to preparations with the original liquid nanocapsules (20.7 ± 1.4 h), regardless of the preparation approach. In addition, the topical nanomedicines prepared with the spray-dried powders presented a significant improvement in tretinoin photostability compared to the formulation containing the non-encapsulated drug. CONCLUSION: This study verified that the addition of the spray-dried powders containing tretinoin-loaded lipid-core nanocapsules to hydrogels did not influence the photoprotection of the drug compared with the preparation procedure using the original liquid suspension.

Spray-dried powders containing tretinoin-loaded engineered lipid-core nanocapsules: development and photostability study.

The influence of the spray-drying process on the ability of engineered lipid-core nanocapsules to protect tretinoin against UV degradation was evaluated. This approach represents a technological alternative to improve the microbiological stability, storage and transport properties of such formulations. Tretinoin-loaded lipid-core nanocapsules or tretinoin-loaded nanoemulsion were dispersed in lactose (10% w/v) and fed in the spray-drier to obtain a solid product (spray-dried powder containing tretinoin-loaded nanocapsules or nanoemulsion--SD-TTN-NCL or SD-TTN-NE, respectively). SD-TTN-NE showed a lower (p < or = 0.05) percentage of encapsulation (89 +/- 1%) compared to SD-TTN-NCL (94 +/- 2%). Redispersed SD-TTN-NCL and SD-TTN-NE showed z-average sizes of 204 +/- 2 nm and 251 +/- 9 nm, which were close to those of the original suspensions (220 +/- 3 nm and 239 +/- 14 nm, respectively). Similar percentage of photodegradation were determined for tretinoin loaded in nanocapsules (26.15 +/- 4.34%) or in the respective redispersed spray-dried powder (28.73 +/- 6.19 min) after 60 min of UVA radiation exposure (p > 0.05). Our experimental design showed for the first time that spray-dried lipid-core nanocapsules are able to protect tretinoin against UVA radiation, suggesting that the drying process did not alter the supramolecular structure of the lipid-core nanocapsules. Such powders are potential intermediate products for the development of nanomedicines containing tretinoin.

Lipid-core nanocapsules as a nanomedicine for parenteral administration of tretinoin: development and in vitro antitumor activity on human myeloid leukaemia cells.

Tretinoin-loaded conventional nanocapsules have showed a significant protection of this drug against UVC radiation. However, this formulation presents a limited stability on storage. We hypothesized that the association of tretinoin to lipid-core nanocapsules could increase the physicochemical stability of such formulations, focusing on the development of a reliable nanomedicine for parenteral administration. However, this advantage should still be accompanied by the known photoprotective effect of conventional polymeric nanocapsules against the exposure of tretinoin to UV radiation. Results showed that tretinoin-loaded lipid-core nanocapsules improved the physicochemical stability of formulations under storage, without changing their ability to protect tretinoin either against UVA or UVC radiation. In addition, the effect of nanoencapsulation on the antiproliferative and differentiation properties of tretinoin was studied on human myeloid leukemia cells (HL60 cells) showing that tretinoin-loaded lipid-core nanocapsules presents a longer antitumor efficiency compared to the free tretinoin. These results allow us to propose the current formulation (tretinoin-loaded lipid-core nanocapsules) as a promising parenteral nanomedicine for the treatment of acute promyelocytic leukaemia.

[Heart rupture in acute myocardial infarct: the advantages of using M-2D color Doppler echocardiography in a coronary intensive therapy unit]. / Rottura di cuore nell'infarto acuto del miocardio: vantaggi dell'uso dell'ecocardiografia M-2D color Doppler in unità di terapia intensiva coronarica.

BACKGROUND: Free-wall rupture of the heart is the second most common cause of death in acute myocardial infarction (AMI), following pump failure. Acute rupture is more common and rapidly fatal, while subacute rupture, which accounts for about 30% of total cases of mortality in AMI, can be diagnosed early by clinical signs with the support of echocardiography in coronary intensive care units. METHODS: From March 1996 to December 1997, 293 patients diagnosed with acute myocardial infarction were admitted to the coronary intensive care unit of our hospital. Of these patients, 71 (23.8%) were treated with thrombolysis within 6 hours of onset of symptoms. All patients were observed daily with M-2D color Doppler echocardiography and in the event of renewed chest pain, electrocardiogram changes, abrupt hypotension, syncope or clinical signs of low output syndrome. RESULTS: We observed 11 cases (3.8%) of free-wall rupture of the heart in acute myocardial infarction with echocardiography, 6 females and 5 males, with a mean age of 74.2 +/- 7.8 years (min. 56-max 84), none of whom had prior AMI. Six of them received thrombolytic therapy, six were hypertensive (54.5%) and three were diabetics (27.2%). Surgical repair was performed in two patients with subacute rupture, but one died a few days later. The echocardiography data at bedside for diagnosis of cardiac rupture were confirmed in 5 patients with autopsy and intraoperatively in two of them. CONCLUSIONS: Routine use of echocardiography in coronary intensive care units allows prompt diagnosis of cardiac rupture in acute myocardial infarction, and in the event of subacute rupture it can accelerate surgical decision-making.

[Percutaneous mitral valvuloplasty in mitral restinosis after surgical commissurotomy]. / Valvuloplastica mitralica percutanea nella restenosi mitralica dopo commissurotomia chirurgica.

UNLABELLED: The frequency of mitral restenosis after surgical commissurotomy has been estimated between 10 and 30% up to 10 years and 85% up to 28 years. Aim of this study was to analyze the results of balloon mitral valvuloplasty (BMV) in a series of patients with previous surgical commissurotomy. METHODS: Between December 1988 and December 1995 432 patients underwent BMV. Of these patients, 30 (6.9%; 10 men, 20 women, aged 53 +/- 12 years) had recurrent mitral stenosis after surgical commissurotomy. Contraindications to BMV were the evidence of left atrial thrombi at transesophageal echocardiography and/or of mitral insufficiency > 2+/4+. The Inoue's single balloon catheter was used for all the procedures. RESULTS: BMV resulted in a decrease in mean mitral gradient from 12.6 +/- 3.8 to 6.1 +/- 2.9 mmHg, and an increase in mitral valve area from 1.03 +/- 0.19 cm2 to 1.95 +/- 0.40 cm2. A mitral insufficiency > or = 3+/4+ occurred in 4/30 BMV (13%). At follow-up (mean 27 +/- 18 months) 20/26 patients (77%) remained clinically improved: 54% were in NYHA class I and 23% in class II. CONCLUSIONS: BMV is an effective short- and long-term procedure for patients with previous surgical commissurotomy, with a low additional risk of complications. Thus, BMV can be considered the treatment of choice in these patients.

[Regression of pulmonary hypertension in mitral stenosis: an echo-hemodynamic study in patients who underwent mitral balloon valvuloplasty]. / Regressione dell'ipertensione polmonare nella stenosi mitralica: studio eco-emodinamico in pazienti sottoposti a valvuloplastica mitralica con palloncino.

BACKGROUND: Reversibility of pulmonary hypertension in patients affected by mitral stenosis is still under question. METHODS: We selected 80 patients (mean age 48 +/- 14) who underwent successful percutaneous mitral valvuloplasty (PMV) for hemodynamic significant mitral stenosis (area < 1.5 cm2) with pulmonary hypertension (mean artery pulmonary pressure--PPM > 25 mm Hg), producing significant increase in mitral valve area (area before PMV = 0.99 +/- 0.23 cm2 vs 2.08 +/- 0.32 cm2 after PMV--p < 0.001) without hemodynamic complications (mitral insufficiency and/or interatrial shunt). Cardiac index, pulmonary arterial pressures, and pulmonary arteriolar resistances were invasively evaluated before and immediately after valvuloplasty. Systolic pulmonary pressure was indirectly monitored by Doppler method in a period from 1 to 3 months after percutaneous mitral valvuloplasty. RESULTS: In general (70 pts.) there was an immediate significant reduction of pulmonary pressure after percutaneous mitral valvuloplasty (mean pulmonary pressure before PMV was 33.9 +/- 7.9 mm Hg vs 26.8 +/- 9.5 mm Hg after PMV, p < 0.01; systolic pulmonary pressure before PMV was 51.5 +/- 10.9 mm Hg vs 43.15 +/- 13.5 mm Hg after PMV--p < 0.01). A small subgroup of 10 pts., older in age (mean 59 +/- 15), manifested no reduction of pulmonary pressure immediately after procedure (mean pulmonary pressure before PMV = 35.2 +/- 8.37 mm Hg vs 36.5 +/- 6 mm Hg after PMV, p: ns; systolic pulmonary pressure before PMV = 58.2 +/- 10.6 mm Hg vs 59.2 +/- 9.6 mm Hg. after PMV, p: ns) and 4 of them (mean age 65 +/- 15) persisting pulmonary hypertension at 1-3 months follow-up (systolic pulmonary pressure before PMV = 58.75 +/- 14 mm Hg, immediately after PMV = 57.8 +/- 12.5 mm Hg, and 1-3 months after PMV = 62.5 +/- 9 mm Hg--p: ns). CONCLUSIONS: Neither severe pulmonary hypertension, nor pulmonary arteriolar resistances but only age seems to be a predictive factor of persisting pulmonary hypertension after percutaneous mitral valvuloplasty in mitral stenosis.

Electrical instability in patients undergoing surgery for atrioventricular septal defect.

Postoperative 24-hour Holter monitoring was performed in 106 patients with atrioventricular septal defect in order to identify the incidence of atrial and ventricular arrhythmias. Of the patients, 72 had separate atrioventricular orifices, including 13 with a small ventricular component to the defect, and 34 patients had a common atrioventricular orifice. Two groups of abnormal patients were found. First, patients with good electrical stability characterized by isolated atrial (9 patients) and ventricular (25 patients) extrasystoles falling in classes I and II of Lown. Second, patients with marked electrical instability characterized in one patient by repetitive atrial extrasystoles, in another by atrial flutter, in 2 by polymorphic ventricular extrasystole and in 8 by couplets or triplets. Electrical instability in individual patients was then compared, by means of logistic regression analysis, with operative, surgical and postoperative variables. There was no incidence of sudden death in our series. After surgical repair, ventricular arrhythmias were more frequent than atrial arrhythmias (33% vs. 10%) and were unrelated to the type of atrioventricular septal defect. Cardiac electrical instability after operation was significantly related to larger operative body size, higher postoperative end diastolic diameter of the right ventricle, larger size of the ventricular septal defect, coexistence of postoperative right bundle branch block and left anterior hemiblock. Conversely, the risk of arrhythmias was reduced by more recent operative data and by greater shortening fraction of the left ventricle.

Outcome of 290 patients with aortic dissection. A 12-year multicentre experience.

Retrospective data regarding 290 patients suffering from spontaneous aortic dissection between January 1976 and June 1987 are reported. Dissection was always documented by retrograde aortography and data were collected from 11 catheterization laboratories operating in North-East Italy. The results show that over a 12-year period there was an increase in cases, an increase in the number of operations and a decline in operative mortality. Multivariate discriminant analysis demonstrated that acute myocardial infarction, persistent shock and persistent central neurologic deficit were significant independent predictors of operative mortality in type A patients. Only persistent shock was significantly related to higher operative mortality in type B patients. Late deaths occurred in 14/118 operated patients, and were mostly secondary (directly or indirectly) to aortic dissection. Discharged patients underwent frequent medical checks and chronically received drugs to control hypertension and reduce inotropism. Most of them (73.7%) were asymptomatic: careful post-operative medical assistance is necessary to guarantee the long-term success of surgical treatment.

[The P loop in atrioventricular septal defect. Embryologico-vectorcardiographic correlation]. / El asa P en el defecto del septum atrio-ventricular. Correlación embriológico-vectocardiográfia.

Atrial vectorcardiograms (vcg) were analysed in 23 patients with partial (n = 15) or complete (n = 8) forms of atrioventricular septal defect (AVSD). The rotation and the projection of the maximum left atrial vector (MLAV) on the frontal plane (FP) and on the horizontal plane (HP) were noted. To assess the possible influence of the degree of left-to-right shunting and the right atrial and right ventricular pressures on the rotation and MLAV projection, these vcg data were correlated with hemodynamic values obtained at the time of preoperative cardiac catheterization. Vcg characteristics of the patients were also compared with those of 25 healthy individuals. No significant differences were noted between the vcg of patients with the partial form and those with the complete form of AVSD. Also, there was no apparent influence of the hemodynamic values on the loop rotation or the MLAV projection in either plane among the patients. However, the MLAV showed a more posteriorly and superior location in the FP and HP than in normal subjects (p = 0.0001). Moreover, 67% of the cases showed a clockwise rotation of the loop in the HP and 33% in the FP; in contrast, normal subjects always showed a counterclockwise rotation in both planes. A more posterior and superior MLAV is consistent with direct observations in human embryos with AVSD which have shown that deficiencies of the posterior portion of the interventricular septum are the basic feature in all cases. The adaptation of the conductive tissue to such deficiency occurs in early phases of cardiac development.