Effect of manufacturing method on the in vitro drug release and adhesive performance of drug-in-adhesive films containing binary mixtures of ibuprofen with poloxamer 188

Drug-in-adhesive acrylic films, containing binary mixtures of ibuprofen:poloxamer 188 in 30:70, 40:60, 50:50, and 60:40 ratios, were prepared by incorporation either as physical mixture (PM), molten mixture (MM), or solid dispersion (SD). Dissolution testing showed that films prepared by MM had higher drug release compared to films prepared by PM, SD, and films containing ibuprofen alone. The MM 50:50 ratio showed the highest drug release (p < 0.05). Examination of the films by differential scanning calorimetry showed melting endotherms from the binary crystalline mixture but not from ibuprofen crystals regardless of the preparation method. Rheological measurements showed that MM films had lower elastic moduli compared to the neat adhesive, due to the plasticizing effect of the dissolved binary mixture. Fourier transfer infrared analysis confirmed the absence of ibuprofen crystal dimers in all films. It was therefore concluded that the MM method provided better mixing of the components providing crystal-free supersaturated films of high thermodynamic activity.     

Sudden arrhythmic death and the cardiomyopathies: Molecular genetics and pathology

Cardiovascular disease is a significant cause of sudden death (SD) requiring autopsy investigation. Cardiomyopathies account for about one half of cases encountered, especially in young people <35 years of age. Among them, inherited cardiomyopathies at risk of SD include hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) as well as primary electrical disorders of the myocardium in the absence of structural abnormalities (channelopathies). The pathologist's task is to make the correct diagnosis and, when dealing with a genetic disease, to trigger widespread cardiological investigation of first-degree family members. This is especially important as SD can be the first and last clinical presentation of the underlying inherited cardiomyopathy and the only medical examination undertaken is that done by the pathologist. An accurate pathological diagnosis, which also includes access to molecular techniques (“molecular autopsy”), will provide vital information for the family in preventing a further tragedy. Therefore proper sampling to allow postmortem DNA analysis as well as accurate morphological evaluation, is mandatory, as recommended in the recently-published guidelines for autopsy investigation of SD from the Association for European Cardiovascular Pathology.     

Immunohistochemical expression of cell-cycle regulators in pediatric embryonal brain tumors

Embryonal tumors constitute the most common malignant brain tumor group in children. Experimental results indicate that genes involved in cell cycle and signal transduction are deregulated in medulloblastoma (MB) and atypical teratoid/rhabdoid tumors (AT/RT). The cell cycle is regulated by protein complexes composed of a regulatory subunit called Cyclin and a catalytic domain named Cyclin-dependent kinase (CDK). Cyclins and CDKs are in turn regulated by cyclin-dependent kinase inhibitors (CDKI) which inhibit cell-cycle progression. Cyclins D and Cyclin E are important for the passage of cells through G1 to S phase. P-27, a member of the universal CDKI family, is important in regulating the G1/S transition. Thus, the purpose of this study was to investigate the expression of p-27, Cyclin D3, and Cyclin E, and their possible prognostic significance in pediatric embryonal brain tumors. We retrospectively evaluated 51 children with embryonal tumors that were treated surgically in our institute. All patients had regular follow up examinations. The streptavidin-biotin HRP method was performed on paraffin sections for detection of p-27, Cyclin D3, and Cyclin E. There were 42 cases of MB and nine cases of AT/RT. Cyclin D3 expression was detected in 11/42?MB and 3/9 AT/RT patients. Cyclin E expression was detected in 28/42?MB and 8/9 AT/RT patients. High expression of Ki-67 (>50?%) and p-27 (>50?%) was observed in 23.8-73.8?% of MB patients. Combined high Ki-67 and p-27 expression was observed in 21.4?% cases of MB. In these cases there was expression of Cyclin E in 88.8?% and Cyclin D3 in 22.2?% of MB. No significant correlation was found between Ki-67 and p-27, Cyclin D3, and E. No correlation was found between Cyclin D3, Cyclin E, p-27, and overall survival. Increased p-27 and Cyclin E expression was detected in a substantial number of MB patients and in nearly all AT/RT patients. Further studies on a larger number of patients are needed to clarify a possible correlation of p-27 and Cyclin E with tumor behavior.     

The impact of maternal- and neonatal-associated factors on human milk's macronutrients and energy

Objectives: To test the impact of specific maternal- and neonatal-associated factors on human milk's macronutrients and energy.

Methods: This study was conducted with the use of a human milk analyzer (HMA, MIRIS, Uppsala, Sweden). Six hundred and thirty samples of raw milk and 95 samples of donor pasteurized milk were delivered from a total of 305 mothers.

Results: A significant inverse correlation of fat, protein and energy content with gestational age and birth weight was established. Fat and energy were lower in colostrum, increased in transitional milk and decreased on the 30th day's mature milk compared to transitional. The rate of protein decline from colostrum to mature milk was lower in premature deliveries compared to that of full-terms, resulting in greater contents of protein in preterm mature milk. The upmost amounts of carbohydrates were found in mature milk of preterm deliveries. A positive correlation was found between maternal age and fat contents. In women with higher post-pregnancy BMI levels greater analogies of fat and energy were presented. In women suffering diet-controlled gestational diabetes (GD), lower protein and higher fat and energy levels were found.

Conclusions: Prematurity, maternal age, diet-controlled GD and high post-pregnancy BMI levels were found to impose statistical significant effect on milk's macronutrients and energy.     

Evaluation of acute/late toxicity and local recurrence in T1–T2 glottic carcinoma treated with accelerated hypofractionated 3D-conformal external beam radiotherapy (3D-CRT)

Background

The aim of the study was to evaluate the efficacy, as well as the acute and late toxicity of an accelerated hypofractionated 3DCRT schedule as radical treatment in patients with organ confined glottic cancer cT1-2N0.

Patients and methods.

Between June of 2004 and September 2010, 47 retrospectively selected patients (29 males, 18 females) diagnosed with organ confined T1 or T2 glottic cancer, were treated with external 3DCRT in an accelerated hypofractionation schedule. The median age was 70 years. A dose of 64.4 Gy in 28 daily fractions was prescribed. The primary study endpoints were to assess the acute and late effects of radiation toxicity, according to the EORTC/ RTOG scale, as well as the therapeutic impact of this schedule in terms of local recurrence.

Results

The median follow up was 36 months. At the end of radiotherapy, grade I, II and III acute toxicity was observed in 34, 9 and4 patients, respectively. Late grade I and II toxicity was observed in 25 and in 8 patients respectively. Only two local recurrences were observed, 15 and 24 months post 3DCRT respectively.

Conclusions

Our radiotherapy schedule achieves a high locoregional control rate with the advantage of voice preservation. The proposed hypofractionated schedule can be recommended as a standard radiotherapy treatment, since these results are comparable with those of conventional fractionation schedules.