Cyclodextrin

The invention provides a method for preparing sulphoalkyl ether-β-cyclodextrin. The method comprises first contacting cyclodextrin with a base to form activated cyclodextrin. The method then comprises separately contacting the activated cyclodextrin with an alkyl sultone to form sulphoalkyl ether-β-cyclodextrin. The activation reaction is carried in batch and the sulphoalkylation reaction is carried out under continuous flow conditions

Lower protein-to-carbohydrate ratio in maternal diet is associated with higher childhood systolic blood pressure up to age four years

The prenatal environment can influence development of offspring blood pressure (BP), which tracks into adulthood. This prospective longitudinal study investigated whether maternal pregnancy dietary intake is associated with the development of child BP up to age four years. Data are from 129 mother-child dyads enrolled in the Women and Their Children\u27s Health study. Maternal diet was assessed using a validated 74-item food frequency questionnaire at 18 to 24 weeks and 36 to 40 weeks, with a reference period of the previous three months. Child systolic and diastolic BP were measured at 3, 6, 9, 12, 24, 36 and 48 months, using an automated BP monitor. Using mixed-model regression analyses adjusted for childhood growth indices, pregnancy intakes of percentage of energy (E%) polyunsaturated fat (β coefficient 0.73; 95% CI 0.003, 1.45; p = 0.045), E% omega-6 fatty acids (β coefficient 0.89; 95% CI 0.09, 1.69; p = 0.03) and protein-to-carbohydrate (P:C) ratio (β coefficient -14.14; 95% CI -27.68, -0.60; p = 0.04) were associated with child systolic BP trajectory up to 4 years. Child systolic BP was greatest at low proportions of dietary protein (<16% of energy) and high carbohydrate (>40% of energy) intakes. There may be an ideal maternal macronutrient ratio associated with optimal infant BP. Maternal diet, which is potentially modifiable, may play an important role in influencing offspring risk of future hypertension

Return to Play After Isolated Meniscal Repairs in Athletes: A Systematic Review.

Background: Meniscal tears are a common knee injury. Isolated meniscal tears are less common; however, unaddressed tears can be troublesome, particularly for athletes. There is currently a lack of data in the literature on athletes returning to play after isolated meniscal repair. Purpose: To evaluate the return to play rate and time to return to play for athletes with isolated meniscal injuries. Study Design: Systematic review; Level of evidence, 4. Methods: A search of the PubMed, EMBASE, and Cochrane electronic databases was conducted to identify studies that reported the time and the rate of return to play in athletes after repair of isolated meniscal tears. Studies were excluded if there was a concomitant anterior cruciate ligament reconstruction, if there was a meniscectomy instead of a meniscal repair, or if the study was a systematic review. Quality assessment and data extraction were performed by 2 examiners. Results: Overall, 21 studies were included in this review. There were 355 athletes (358 knees) with a mean age of 22.5 years (range, 9-68 years). A sex breakdown was noted in 16 of the 21 (76.2%) studies with 224 men and 71 women. The specific repair technique was described in 259 (72.3%) knees. Of the total knees, 109 (30.4%) had an open repair, 128 (35.8%) had an inside-out arthroscopic technique repair, and 22 (6.1%) had an all-inside arthroscopic technique repair. Complications were addressed in 11 studies, with 13 out of 155 (8.4%) patients across the 11 articles having a postoperative complication. Of the total 355 patients, 295 (83.1%) returned to play, and 17 of these 21 (81.0%) articles reported the time it took for athletes to return to play, with a mean return of 8.7 months. Conclusion: The study results indicate that return to play rates after isolated meniscal repair are high, with an overall return to play rate of 83.1% and a mean return to play time of 8.7 months. However, the limited number of studies, particularly ones with larger patient numbers, highlights the need for further investigation regarding isolated meniscal repair in athletes

Preparation of Rapamycin and methyl-β-cyclodextrin complexes using a single-step, organic solvent-free supercritical fluid process: An approach to enhance the solubility and dissolution properties

The purpose of this study was to evaluate a single-step, organic solvent-free supercritical fluid process for the preparation of rapamycin-methyl-β-cyclodextrin complexes with an express goal to enhance the dissolution properties of rapamycin. The complexes were prepared by supercritical carbon dioxide processing, co-evaporation, freeze drying and physical mixing. The prepared complexes were then analyzed by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, solubility and dissolution studies. Computational molecular docking studies were performed to study the formation of molecular inclusion complexation of rapamycin with methyl-β-cyclodextrin. Rapamycin exists in a highly crystalline solid form. Physical mixing of rapamycin and methyl-β-cyclodextrin appeared not to reduce the degree of crystallinity of the drug. The co-evaporated and freeze dried complexes had a lower degree of crystallinity than the physical mix; however the lowest degree of crystallinity was achieved in complexes prepared by supercritical carbon dioxide processing method. All the binary mixtures with Me-β-CD exhibited a faster and greater extent of drug dissolution than the drug alone. Products obtained by the supercritical carbon dioxide processing method exhibited the highest apparent drug dissolution. Information obtained from the characterization tests suggest complete complexation or amorphization of rapamycin and Me-β-CD prepared by supercritical carbon dioxide processing method. Therefore, a solid inclusion method using supercritical carbon dioxide carrier proved to be a novel and useful complexation method for rapamycin into Me-β-CD. Furthermore, since this method has no toxic solvent residue, products obtained by this method should provide minimal side effects in humans, compared to those obtained by techniques, which require the use of perilous organic solvents

Continuous tank reactor synthesis of highly substituted sulphobutylether β-cyclodextrins

Batch synthesis of sulphobutyl ether β-cyclodextrin (also known as SBE-β-CD or SBECD) is a process effectively divided into three main stages, i.e. initial reagent dissolution, a sulphoalkylation reaction and final reaction quenching. This reaction is followed by downstream processing and purification, and ultimate isolation of the solid SBECD material. However, a feature associated with using this synthetic method is that a high proportion of lower substituted SBECD is observed. There is therefore a need to provide an improved synthetic method for producing higher substituted cyclodextrins. The authors here present a Continuous Tank Reactor (CTR) method for preparing sulphobutyl ether-cyclodextrins. The method comprises first contacting cyclodextrin with a base to form activated cyclodextrin. The method then involves separately contacting the activated cyclodextrin with an 1,4-butane sultone to form sulphoalkyl ether-cyclodextrin. The activation reaction is carried out in batch synthesis mode and the sulphoalkylation reaction is carried out under continuous flow conditions resulting in a novel method for the synthesis of highly derivatised cyclodextrins. The work is particularly concerned with producing controlled substitution in sulphobutyl ether β-cyclodextrins and novel compositions of highly substituted sulphoalkyl ether β-cyclodextrins are described

Construction and physiochemical characterisation of a multi-composite, potential oral vaccine delivery system (VDS)

An increasing human population requires a secure food supply and a cost effective, oral vaccine delivery system for livestock would help facilitate this end. Recombinant antigen adsorbed onto silica beads and coated with myristic acid, was released (∼15% (w/v)) over 24 h at pH 8.8. At pH 2, the myristic acid acted as an enteric coating, protecting the antigen from a variety of proteases. The antigen adsorbed onto silica particles, coated in myristic acid had a conserved secondary structure (measured by circular dichroism (CD) spectroscopy) following its pH-triggered release. Small angle neutron scattering (SANS) was used to measure the thickness of the adsorbed antigen, finding that its adsorbed conformation was slightly greater than its solution radius of gyration, i.e. 120–160 Å. The addition of myristic acid led to a further increase in particle size, with scattering data consistent with an acid thickness slightly greater than a monolayer of fully extended alkyl chains and a degree of hydration of around 50%. Whilst adsorbed onto the silica and coated in myristic acid, the protein was stable over 14 days at 42 °C, indicating a reduced need for cold chain storage. These data indicate that further investigation is warranted into the development of this technology

Progress and prospects for event tourism research

This paper examines event tourism as a field of study and area of professional practice updating the previous review article published in 2008. In this substantially extended review, a deeper analysis of the field’s evolution and development is presented, charting the growth of the literature, focusing both chronologically and thematically. A framework for understanding and creating knowledge about events and tourism is presented, forming the basis which signposts established research themes and concepts and outlines future directions for research. In addition, the review article focuses on constraining and propelling forces, ontological advances, contributions from key journals, and emerging themes and issues. It also presents a roadmap for research activity in event tourism