Reliability of tumor primary cultures as a model for drug response prediction: expression profiles comparison of tissues versus primary cultures from colorectal cancer patients

Purpose  

Since primary tumor cells from patients have been used as a model for assessment of drug response for individual patients, this study aims to evaluate the reliability of such a model in colorectal cancer (CRC) in predicting the response of tumor tissues through comparison of their expression profiles.     

Anatomy of sodium hypochlorite accidents involving facial ecchymosis—A review

Objectives

Root canal treatment forms an essential part of general dental practice. Sodium hypochlorite (NaOCl) is the most commonly used irrigant in endodontics due to its ability to dissolve organic soft tissues in the root canal system and its action as a potent antimicrobial agent. Although NaOCl accidents created by extrusion of the irrigant through root apices are relatively rare and are seldom life-threatening, they do create substantial morbidity when they occur.

Methods

To date, NaOCl accidents have only been published as isolated case reports. Although previous studies have attempted to summarise the symptoms involved in these case reports, there was no endeavour to analyse the distribution of soft tissue distribution in those reports. In this review, the anatomy of a classical NaOCl accident that involves facial swelling and ecchymosis is discussed.

Results

By summarising the facial manifestations presented in previous case reports, a novel hypothesis that involves intravenous infusion of extruded NaOCl into the facial vein via non-collapsible venous sinusoids within the cancellous bone is presented.

Conclusions

Understanding the mechanism involved in precipitating a classic NaOCl accident will enable the profession to make the best decision regarding the choice of irrigant delivery techniques in root canal débridement, and for manufacturers to design and improve their irrigation systems to achieve maximum safety and efficient cleanliness of the root canal system.     

API ionic liquids: probing the effect of counterion structure on physical form and lipid solubility

Lipid based formulations (LBFs) are extensively utilised as an enabling technology in drug delivery. The use of ionic liquids (ILs) or lipophilic salts (LS) in drug delivery has also garnered considerable interest due to unique solubility properties. Conversion of active pharmaceutical ingredients (API) to ILs by pairing with an appropriately lipophilic counterion has been shown to decrease melting point of the salt complex and improve solubility in LBFs. However, the relationship between the structure of the counterion, the physicochemical properties of the resulting salts and solubility in LBFs has not been systematically explored. This study investigates the relationship between alkyl sulfate counterion structure and melting temperature (T_m or T_g) in addition to LBF solubility, utilizing cinnarizine and lumefantrine as model weakly basic APIs. Three series of structurally diverse alkyl sulfate counterions were chosen to probe this relationship. Pairing cinnarizine and lumefantrine with a majority of these alkyl sulfate counterions resulted in a reduction in melting temperature and enhanced solubility in model medium chain and long chain LBFs. The chain length of the alkyl sulfate plays a crucial role in performance, and consistently branched alkyl sulfate counterions perform better than straight chain alkyl sulfate counterions, as predicted. Most interestingly, trends in counterion performance were found to be consistent across two APIs with disparate chemical structures. The findings from this study will facilitate the design of counterions which enhance solubility of ionisable drugs and unlock the potential to develop compounds previously restrained by poor solubility.

Structure/property relationship of API IL counterions and salt physicochemical properties are investigated, the results highlight the complex interplay involved.