Diving-related fatalities: multidisciplinary,experience-based investigation

Forensic Science, Medicine and Pathology - To describe the technical characteristics of fatal diving mishaps and to elucidate the causes of death using a sequence analysis and a multidisciplinary...     

Improved pharmacokinetic profile of lipophilic anti-cancer drugs using ανβ3-targeted polyurethane-polyurea nanoparticles

Glutathione degradable polyurethane-polyurea nanoparticles (PUUa NP) with a disulfide-rich multiwalled structure and a cyclic RGD peptide as a targeting moiety were synthesized, incorporating a very lipophilic chemotherapeutic drug named Plitidepsin. In vitro studies indicated that encapsulated drug maintained and even improved its cytotoxic activity while in vivo toxicity studies revealed that the maximum tolerated dose (MTD) of Plitidepsin could be increased three-fold after encapsulation. We also found that pharmacokinetic parameters such as maximum concentration (Cmax), area under the curve (AUC) and plasma half-life were significantly improved for Plitidepsin loaded in PUUa NP. Moreover, biodistribution assays in mice showed that RGD-decorated PUUa NP accumulate less in spleen and liver than non-targeted conjugates, suggesting that RGD-decorated nanoparticles avoid sequestration by macrophages from the reticuloendothelial system. Overall, our results indicate that polyurethane-polyurea nanoparticles represent a very valuable nanoplatform for the delivery of lipophilic drugs by improving their toxicological, pharmacokinetic and whole-body biodistribution profiles.     

Primary hyperparathyroidism, insulin resistance, and cardiovascular disease: a review

The presentation of primary hyperthyroidism (PHPT) has changed substantially in the last decade. Before the introduction of routine calcium measurement in most automated biochemistry serum analyzers, it usually was diagnosed after renal and bony lesions already were present. Nowadays, its presentation is practically asymptomatic. Nevertheless, the cardiovascular morbidity and mortality of mild to moderate forms of PHPT reportedly are increasing. Individuals who have mild to moderate forms of PHPT have an increased risk for enduring cardiovascular disease, arterial hypertension, left ventricular hypertrophy, myocardial and valvular calcifications, altered vascular reactivity, and cardiac conduction. Finally, they also reveal alterations in carbohydrate metabolism, insulin resistance, dyslipidemia, and body composition.     

One-year follow-up of first consecutive 100 zirconia dental implants in humans: a comparison of 2 different rough surfaces

PURPOSE: The aim of this study was to evaluate the success rate of 100 consecutive zirconia dental implants with 2 different rough surfaces after 1 year of follow-up. MATERIALS AND METHODS: One-piece zirconia dental implants (CeraRoot, Barcelona, Spain) with 1 of 2 different roughened surfaces were designed and manufactured for this study. Five different implant designs were manufactured. Standard or flapless surgical procedures were used for implant placement. Simultaneous bone augmentation or sinus elevation were performed in the cases where bone height or width was insufficient. Implants in the anterior region (canine to canine) were immediately restored with provisional prostheses. Implants placed using less than 35 N torque were splinted with composite resin using an etched and bonded approach to the neighboring teeth or implants to minimize implant mobility and failure. Definitive all-ceramic restorations were placed 4 months after implant placement (8 months for implants where bone augmentation or sinus elevation was performed). RESULTS: The study included 36 patients with a mean age of 50 years. The overall implant success rate after 1 year of follow-up was 98% in both the coated and noncoated groups. CONCLUSIONS: From the preliminary results of this investigation, it can be concluded that zirconia dental implants with roughened surfaces might be a viable alternative for tooth replacement. Further follow-up is needed to evaluate the long-term success rates of the implant surfaces studied.     

Determination of stress-induced degradation products of cetirizine dihydrochloride by a stability-indicating RP-HPLC method

Background

A new, simple and accurate stability-indicating reverse phase high performance liquid chromatography method was developed and validated during the early stage of drug development of an oral lyophilizate dosage form of cetirizine dihydrochloride.

Methods

For RP-HPLC analysis it was used an Eclipse XDB C8 column 150 mm × 4.6 mm, 5 μm (Agilent columns, Barcelona, Spain) as the stationary phase with a mobile phase consisted of a mixture of 0.2 M K₂HPO4 pH 7.00 and acetonitrile (65:35, v/v) at a flow rate of 1 mL min ⁻¹. Detection was performed at 230 nm using diode array detector. The method was validated in accordance with ICH guidelines with respect to linearity, accuracy, precision, specificity, limit of detection and quantification.

Results

The method results in excellent separation between the drug substance and its stress-induced degradation products. The peak purity factor is >950 for the drug substance after all types of stress, which confirms the complete separation of the drug substance peak from its stress induced degradation products.Regression analysis showed r² > 0.999 for cetirizine dihydrochloride in the concentration range of 650 μg mL ⁻¹ to 350 μg mL⁻¹ for drug substance assay and a r² > 0.999 in the concentration range of 0.25 μg mL⁻¹ to 5 μg mL⁻¹ for degradation products. The method presents a limit of detection of 0.056 μg mL ⁻¹ and a limit of quantification of 0.25 μg mL⁻¹. The obtained results for precision and accuracy for drug substance and degradation products are within the specifications established for the validation of the method.

Conclusions

The proposed stability-indicating method developed in the early phase of drug development proved to be a simple, sensitive, accurate, precise, reproducible and therefore useful for the following stages of the cetirizine dihydrochloride oral lyophilizate dosage form development.