Recent developments in advanced thermal analysis: sample controlled thermal analysis

The determination of the key physical and chemical properties of a new material is essential.The melting point, glass transition temperature, the number and identification of the different phases it may have, and the temperatures at which they are formed are all of great value, not only in assessing its practical pharmaceutical potential but also as they can form the basis of many routine QC procedures

Predicting human intestinal absorption in the presence of bile salt with micellar liquid chromatography

Understanding intestinal absorption for pharmaceutical compounds is vital to estimate bioavailability and therefore the in vivo potential of a drug. This study considers the application of micellar liquid chromatography (MLC) to predict passive intestinal absorption with a selection of model compounds. MLC is already known to aid prediction of absorption using simple surfactant systems however, with this study the focus was on the presence of a more complex, bile salt surfactant, as would be encountered in the in vivo environment. As a result, MLC using a specific bile salt has been confirmed as an ideal in vitro system to predict the intestinal permeability for a wide range of drugs, through the development of a quantitative partition-absorption relationship. MLC offers many benefits including environmental, economic, time-saving and ethical advantages compared with the traditional techniques employed to obtain passive intestinal absorption values

Prediction of human intestinal absorption using micellar liquid chromatography with an aminopropyl stationary phase

The extent of human intestinal absorption (HIA) for a drug is considered to be an important pharmacokinetic parameter which must be determined for orally administered drugs. Traditional experimental methods relied upon animal testing and are renowned for being time consuming, expensive as well as being ethically unfavourable. As a result, developing alternative methods to evaluate a drug's pharmacokinetics is crucial. Micellar liquid chromatography (MLC) is considered to be one of these methods that can replace the use of animals in prediction of HIA. In this study, the combination of an aminopropyl column with the biosurfactant sodium deoxycholate (NaDC) bile salt were used in the experimental determination of micelle-water partition coefficients (log Pmw) for a group of compounds. Multiple linear regression (MLR) was then used for the prediction of HIA using the experimentally determined log Pmw along with other molecular descriptors leading to the construction of a model equation of R2= 85 % and a prediction power represented by R2Pred. =72 %. The use of MLC with an aminopropyl column in combination with NaDC was found to be a good method for the prediction of human intestinal absorption, providing data for a far wider range of compounds compared with previous studies

Effect of decomposition on clothing damage evidence: A preliminary study

Textiles are generally present when a crime takes place and, in some cases, may be directly linked to a crime. Due to changes that occur to fabric over time, there is a risk of clothing damage being misinterpreted, and vital evidence being missed. This study is the first of a number of studies exploring the effect of decomposition upon clothing damage evidence following a stabbing. Sections of porcine tissue were wrapped in fabric in which stab cuts had been created, and left exposed to the environment alongside negative controls. Images of the damage were taken before and after a period of decomposition over two weeks. When compared to the negative controls, these images clearly demonstrated that there was a significant amount of alteration to the clothing damage evidence e.g. loose and fraying yarns, following a period of decomposition. Quantification of the fraying to the damage showed a statistically significant increase of the amount of fraying (p=<0.05)

Parameters affecting ion intensities in transmission-mode Direct Analysis in Real-Time mass spectrometry

A survey of the effect of temperature, transmission module material and analysis time on ion intensities in transmission mode direct analysis in real time mass spectrometry is presented. Ion intensity profiles obtained for two related compounds are similar when analysed separately but are very different when analysed as a mixture

High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease.

BACKGROUND: The gut microbiota is thought to play a key role in the development of the inflammatory bowel diseases Crohn's disease (CD) and ulcerative colitis (UC). Shifts in the composition of resident bacteria have been postulated to drive the chronic inflammation seen in both diseases (the "dysbiosis" hypothesis). We therefore specifically sought to compare the mucosa-associated microbiota from both inflamed and non-inflamed sites of the colon in CD and UC patients to that from non-IBD controls and to detect disease-specific profiles. RESULTS: Paired mucosal biopsies of inflamed and non-inflamed intestinal tissue from 6 CD (n = 12) and 6 UC (n = 12) patients were compared to biopsies from 5 healthy controls (n = 5) by in-depth sequencing of over 10,000 near full-length bacterial 16S rRNA genes. The results indicate that mucosal microbial diversity is reduced in IBD, particularly in CD, and that the species composition is disturbed. Firmicutes were reduced in IBD samples and there were concurrent increases in Bacteroidetes, and in CD only, Enterobacteriaceae. There were also significant differences in microbial community structure between inflamed and non-inflamed mucosal sites. However, these differences varied greatly between individuals, meaning there was no obvious bacterial signature that was positively associated with the inflamed gut. CONCLUSIONS: These results may support the hypothesis that the overall dysbiosis observed in inflammatory bowel disease patients relative to non-IBD controls might to some extent be a result of the disturbed gut environment rather than the direct cause of disease. Nonetheless, the observed shifts in microbiota composition may be important factors in disease maintenance and severity

Formation of a bile salt-drug hydrogel to predict human intestinal absorption

The unique character of bile salts to self-assemble into hydrogels in the presence of halide salts was exploited in this work to facilitate the prediction of human intestinal absorption (%HIA) for a set of 25 compounds. This was achieved by firstly incorporating each compound separately within the process of gel formation to create a series of gel-drug membranes. Scanning Electron Microscopy (SEM) analysis of the freeze-dried samples of the blank bile salt hydrogels and drug loaded bile salt hydrogels indicated a unique microstructure made of a network of intertwined fibrils. Drug-loaded sodium deoxycholate (NaDC) hydrogels were then utilised as the donor phase to study permeability using flow-through and static diffusion cells. The resulting values of the release-permeability coefficient (Kp) were then analysed, along with other molecular descriptors, for the prediction of human intestinal absorption (%HIA) using multiple linear regression (MLR). Overall, when comparing predicted values (using the systems presented in this study) with known literature values, it can be seen that both methods (i.e. using static and flow through cells) had good predictability with R2PRED. values of 79.8 % and 79.7 % respectively. This study therefore proposes a novel, accurate and precise way to predict human intestinal absorption for compounds of pharmaceutical interest using a simple in vitro permeation system. It is important to develop alternatives to the current methods used in prediction of HIA which are expensive and time consuming or include the use of animals. Therefore, the proposed method in this study being economic and time saving provides superiority over these current methods and suggests the possibility of its use as an alternate to such methods for prediction of HIA

Effectiveness and safety of vedolizumab in inflammatory bowel disease patients aged 60 and over: an observational multicenter UK experience.

BACKGROUND: The GEMINI trials established the efficacy of vedolizumab in moderate-to-severe inflammatory bowel disease (IBD) and demonstrated a favorable safety profile, suggesting it may be advantageous in older patients at greater risk of treatment-related complications. However, there is a paucity of data exploring the outcomes of vedolizumab in this group. Our objective was to determine the clinical effectiveness and safety of vedolizumab in older IBD patients within a real-world multicenter UK cohort. METHODS: A retrospective review of electronic records across 6 UK hospitals was undertaken to evaluate the clinical effectiveness and safety outcomes of vedolizumab in IBD patients aged ≥60 at start of therapy. Rates of clinical response, remission and corticosteroid-free remission were assessed at weeks 14 and 52, using validated clinical indices, and were compared to historical controls from real-world vedolizumab-treated cohorts unstratified by age. RESULTS: Of 74 patients aged 60 years or above (median 66 years), 48 were included in our effectiveness analysis (29 ulcerative colitis, 19 Crohn's disease). Rates of clinical response, remission and corticosteroid-free remission at week 14 were 64%, 48% and 30%, respectively. By week 52, the rates of clinical response, remission, and corticosteroid-free remission were 52%, 38%, and 32%, respectively. Six (8%) patients experienced adverse effects. Effectiveness and safety outcomes were comparable to those of age-unstratified vedolizumab-treated cohorts. CONCLUSION: Our 1-year outcome data suggests that vedolizumab is safe and effective in older IBD patients and broadly comparable to cohorts unselected by age