Effects of lipid composition and preparation conditions on physical-chemical properties, technological parameters and in vitro biological activity of gemcitabine-loaded liposomes

The effects of lipid composition and preparation conditions on the physicochemical and technological properties of gemcitabine-loaded liposomes, as well as the in vitro anti-tumoral activity of various liposome formulations were investigated. Three liposome formulations were investigated: DPPC/Chol/Oleic acid (8:3:1 molar ratio, liposomes A), DPPC/Chol/DPPS (6:3:1 molar ratio, liposomes B) and DPPC/Chol/DSPE-MPEG (6:3:1 molar ratio, liposomes C). Multilamellar liposomes were prepared by using the TLE, FAT and DRV methods, while small unilamellar liposomes were obtained by extrusion through polycarbonate filters. Light scattering techniques were used to characterize liposome formulations. Loading capacity and release profiles of gemcitabine from various liposome formulations were also investigated. Caco-2 cells were used to evaluate in vitro the antitumoral activity of gemcitabine-loaded liposomes with respect to the free drug and also the intracellular drug uptake. Preparation methods and liposome lipid composition influenced both physicochemical parameters and drug delivery features. Liposomes with a size ranging from 200 nm to 7 microm were obtained. The gemcitabine entrapment was higher than that expected probably due to an interaction with the liposome lipid components. The following decreasing loading capacity order was observed: liposome B>liposome C>liposome A. Gemcitabine release from various liposome formulations is modulated by two different processes, i.e. desorption from and permeation through liposomal bilayers. MTT assay showed a greater cytotoxic effect of gemcitabine-loaded liposomes with respect to the free drug. The following decreasing anticancer activity order was observed between the various liposome formulations: liposome C>liposome A>liposome B. The increased anticancer activity is correlated to the ability of the colloidal carrier to increase the intracellular drug uptake. Due to the encouraging results and to the high liposome modularity various applications of potential therapeutic relevance can be envisaged for liposomes.     

A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB

The purpose of this investigation was to explore the potentiality of a novel animal model to be used for the in vivo evaluation of the ability of a drug delivery system to promote the passage through the blood–brain barrier (BBB) and/or to improve the brain localization of a bioactive compound. A Tween 80^®-coated poly-l-lactid acid nanoparticles was used as a model of colloidal drug delivery system, able to trespass the BBB. Tacrine, administered in LiCl pre-treated rats, induces electrocorticographic seizures and delayed hippocampal damage. The toxic effects of tacrine-loaded poly-l-lactid acid nanoparticles (5 mg/kg), a saline solution of tacrine (5 mg/kg) and an empty colloidal nanoparticle suspension were compared following i.p. administration in LiCl-pre-treated Wistar rats. All the animals treated with tacrine-loaded nanoparticles showed an earlier outcome of CNS adverse symptoms, i.e. epileptic onset, with respect to those animals treated with the free compound (10 min vs. 22 min respectively). In addition, tacrine-loaded nanoparticles administration induced damage of neuronal cells in CA1 field of the hippocampus in all treated animals, while the saline solution of tacrine only in 60% of animals. Empty nanoparticles provided similar results to control (saline-treated) group of animals. In conclusion, the evaluation of time-to-onset of symptoms and the severity of neurodegenerative processes induced by the tacrine–lithium model of epilepsy in the rat, could be used to evaluate preliminarily the capability of a drug delivery system to trespass (or not) the BBB in vivo.     

The role of the endoscopic transsphenoidal approach in pediatric neurosurgery

The endoscopic endonasal transsphenoidal approach to the sellar region for the removal of pituitary adenomas and of other neoplasms in the same area has proved its reliability and effectiveness for the very wide vision it offers, coupled with minimal surgical trauma. Indications and advantages of such a technique are reported, focused on the treatment of lesions of the sellar and parasellar environment in pediatric age-group patients, and based on a consecutive series of 100 patients, 3 of them adolescents, treated during the last 3 years.     

Left ventricular mass regression after aortic valve replacement with 17-mm St Jude Medical mechanical prostheses in isolated aortic stenosis

OBJECTIVE: The present study investigated the outcomes of aortic valve replacement with 17-mm mechanical prostheses in patients with isolated aortic stenosis. METHODS: Between January 1997 and January 2003, 35 patients (mean age, 63.4 +/- 17 years; median age, 70 years; age range, 16-84 years) underwent isolated aortic valve replacement with a 17-mm St Jude Medical Hemodynamic Plus (16 [45.7%] patients) or a St Jude Medical Regent prosthesis (19 [54.3%] patients). The paired Student t test or the paired Wilcoxon rank sum test were used to compare preoperative with follow-up echocardiographic measurements. RESULTS: Thirty-two (91.4%) patients were female, mean height was 154.4 +/- 8.3 cm, mean weight was 62.2 +/- 9.2 kg, and mean body surface area was 1.59 +/- 0.13 m 2 . The preoperative average New York Heart Association class was 2.8 +/- 0.8. The mean preoperative left ventricular mass index was 135.2 +/- 31 g/m 2 . Preoperative echocardiography showed an average gradient of 65.7 +/- 19.2 mm Hg (mean) and 103.6 +/- 30.7 mm Hg (peak) and a mean indexed effective orifice area of 0.40 +/- 0.1 cm 2 /m 2 . Echocardiographic follow-up time averaged 28.2 +/- 22.7 months (range, 13-72 months). Follow-up was 100% complete (1131.7 patient-months). Hospital mortality was 8.6% (3 patients). Actuarial 5-year survival was 94.7%. The mean postoperative New York Heart Association class was 1.13 +/- 0.34 ( P < .001), with 27 (87.1%) patients in class I and 4 patients in class II. A significant regression of the indexed left ventricular mass was found (postoperative mean value, 107.8 +/- 22.8 g/m 2 ; P < .0001), despite a mean indexed effective orifice area of 0.67 +/- 0.14 cm 2 /m 2 (median, 0.66 cm 2 /m 2 ). CONCLUSIONS: Selected patients with aortic stenosis can experience satisfactory clinical improvement and significant indexed left ventricular mass regression after aortic valve replacement with modern small-diameter bileaflet prostheses.     

Treatment of type B aortic dissection: endoluminal repair or conventional medical therapy?

OBJECTIVE: To evaluate the mid-term results of endovascular stent-grafting for type B aortic dissection, in comparison with those of standard medical therapy in uncomplicated cases. METHODS: Between January 1999 and 2004, among 56 patients (mean age 59.5+/-11.5 years) with type B aortic dissection, hypotensive medical therapy was the only treatment in 28 uncomplicated cases, (group A), while stent-graft implantation was performed in 28 patients with uncontrolled hypertension, persistent pain or evidence of dissection progression or complication (group B). In 14 cases (50%) the procedure was performed in an acute setting. Stent-grafting procedures were monitored with intraoperative trans-esophageal echocardiography and cine-angiography. CT scan and trans-esophageal echocardiography were performed before hospital discharge, at 6 and 12 months and then yearly. RESULTS: Follow-up (range 1-61 months, average 18.1+/-16.9 months) was 100% complete. In-hospital mortality was 10.7% (three patients, all belonging to Group B; P=0.24). No spinal cord injuries were observed. Early endoleak occurred in one patient (3.5%). Mid-term mortality was lower in Group B, although the difference was not significant (10.7 versus 14.3% in Group A, P=0.71). Follow-up CT scans evidenced complete thrombosis of the false lumen in 75% cases in Group B, 10.7% in Group A (P=0.0001), and an aneurismal dilatation of the descending aorta in 3.5% cases in Group B, 28.5% in Group A (P=0.02). CONCLUSIONS: Although with still considerable early mortality, endovascular stent-graft implantation is an effective option for the treatment of complicated type B aortic dissection. Endovascular treatment achieved a better mid-term fate of the descending thoracic aorta than medical therapy alone, even in patients with worse preoperative conditions.     

The clinical significance of body composition and anthropometric evaluation in athletes

Body composition and anthropometric assessment provide the sports physician with useful information on the health state of the athlete and with some necessary elements to plan specific training loads in the most appropriate way. In practice, the chemical composition of an athlete’s body (especially those who carry out 1–2 daily workouts) is always in a physiologic condition that we can define as “dynamic” (concentration of electrolytes, hydration state and relationship between intra-and extra-cellular water, stages of growth of muscle mass and/or reduction of fat mass, etc.), with the exception of few times of year, such as the short resting break before resuming training. As a consequence, a real “baseline” (or “stationary”) physiological state, allowing to detect the parameters of body composition under the same conditions several times during the year, is only rarely achieved. In this paper, we wanted to review the most interesting parameters and methods for the evaluation of athletes’ body composition, and underline their potential applications, possible advantages, theoretical and practical limitations.