Dietary fibre and phytate; a balancing act. Results from 3 time points in a British Birth Cohort

An investigation was carried out to determine whether there were significant changes in the intake of dietary fibre (non-starch polysaccharide; NSP) and phytate of adult men and women in the UK from 1982 (aged 36 years) to 1999 (aged 53 years). The 1253 subjects studied were members of the Medical Research Council National Survey of Health and Development; a longitudinal study of a nationally representative cohort of births in 1946. Food intake was recorded in a 5-day diary at age 36 years in 1982, 43 years in 1989 and 53 years in 1999. The food composition database was amended with revised values for phytate. Outcome measures were mean intakes of total NSP and phytate by year, gender and food source. There were significant changes in total NSP and phytate intake over the 3 time-points. Intakes of NSP rose significantly between 1982 and 1999 for men and women but phytate intakes rose significantly only between 1989 and 1999. Cereal foods were the most important source of both NSP and phytate. Between 1989 and 1999 there was a significant increase in the contribution from pasta, rice and other grains. This study shows that an increase in dietary fibre that is in accordance with dietary guidelines would almost inevitably be accompanied by a rise in phytate. The increased dietary phytate is discussed in relation to its recognised inhibition of mineral absorption and its merits with regard to protection against some cancers and other diseases of an ageing population

An Analytical Model for Rotator Cuff Repairs

Background Currently, natural and synthetic scaffolds are being explored as augmentation devices for rotator cuff repair. When used in this manner, these devices are believed to offer some degree of load sharing; however, no studies have quantified this effect. Furthermore, the manner in which loads on an augmented rotator cuff repair are distributed among the various components of the repair is not known, nor is the relative biomechanical importance of each component. The objectives of this study are to (1) develop quasi-static analytical models of simplified rotator cuff repairs, (2) validate the models, and (3) predict the degree of load sharing provided by an augmentation scaffold. Methods The individual components of the repair constructs were modeled as non-linear springs, and the model equations were formulated based on the physics of springs in series and parallel. The model was validated and used to predict the degree of load sharing provided by a scaffold. Parametric sensitivity analysis was used to identify which of the component(s)/parameter(s) most influenced the mechanical behavior of the augmented repair models. Findings The validated models predict that load will be distributed ∼ 70–80% to the tendon repair and ∼ 20–30% to the augmentation component. The sensitivity analysis suggests that the greatest improvements in the force carrying capacity of a tendon repair may be achieved by improving the properties of the bone–suture–tendon interface. Future studies will perform parametric simulation to illustrate the manner in which changes to the individual components of the repair, representing different surgical techniques and scaffold devices, may influence the biomechanics of the repair construct

An Analytical Model for Rotator Cuff Repairs

Background Currently, natural and synthetic scaffolds are being explored as augmentation devices for rotator cuff repair. When used in this manner, these devices are believed to offer some degree of load sharing; however, no studies have quantified this effect. Furthermore, the manner in which loads on an augmented rotator cuff repair are distributed among the various components of the repair is not known, nor is the relative biomechanical importance of each component. The objectives of this study are to (1) develop quasi-static analytical models of simplified rotator cuff repairs, (2) validate the models, and (3) predict the degree of load sharing provided by an augmentation scaffold. Methods The individual components of the repair constructs were modeled as non-linear springs, and the model equations were formulated based on the physics of springs in series and parallel. The model was validated and used to predict the degree of load sharing provided by a scaffold. Parametric sensitivity analysis was used to identify which of the component(s)/parameter(s) most influenced the mechanical behavior of the augmented repair models. Findings The validated models predict that load will be distributed ∼ 70–80% to the tendon repair and ∼ 20–30% to the augmentation component. The sensitivity analysis suggests that the greatest improvements in the force carrying capacity of a tendon repair may be achieved by improving the properties of the bone–suture–tendon interface. Future studies will perform parametric simulation to illustrate the manner in which changes to the individual components of the repair, representing different surgical techniques and scaffold devices, may influence the biomechanics of the repair construct

Conductivity of Doped Two-Leg Ladders

Recently, conductivity measurements were performed on the hole-doped two-leg ladder material Sr_{14-x}Ca_xCu_{24}O_{41}. In this work, we calculate the conductivity for doped two-leg ladders using a model of hole-pairs forming a strongly correlated liquid - a single component Luttinger liquid - in the presence of disorder. Quantum interference effects are handled using renormalization group methods. We find that our model can account for the low energy features of the experimental results. However, at higher energies the experiments show deviations from the predictions of this model. Using the results of our calculations as well as results on the ground state of doped two-leg ladders, we suggest a scenario to account for the higher energy features of the experimental results.Comment: 5 pages, 3 postscript figure

Effect of poly(ethylene glycol) on insulin stability and cutaneous cell proliferation in vitro following cytoplasmic delivery of insulin-loaded nanoparticulate carriers – A potential topical wound management approach

We describe the development of a nanoparticulate system, with variation of poly(ethylene glycol) (PEG) content, capable of releasing therapeutic levels of bioactive insulin for extended periods of time. Recombinant human insulin was encapsulated in poly(d,l-lactide-co-glycolide) nanoparticles, manufactured with variation in poly(ethylene glycol) content, and shown to be stable for 6days using SDS-PAGE, western blot and MALDI MS. To determine if insulin released from this sustained release matrix could stimulate migration of cell types normally active in dermal repair, a model wound was simulated by scratching confluent cultures of human keratinocytes (HaCaT) and fibroblasts (Hs27). Although free insulin was shown to have proliferative effect, closure of in vitro scratch fissures was significantly faster following administration of nano-encapsulated insulin. This effect was more pronounced in HaCaT cells when compared to Hs27 cells. Variation in PEG content had the greatest effect on NP size, with a lesser influence on scratch closure times. Our work supports a particulate uptake mechanism that provides for intracellular insulin delivery, leading to enhanced cell proliferation. When placed into an appropriate topical delivery vehicle, such as a hydrogel, the extended and sustained topical administration of active insulin delivered from a nanoparticulate vehicle shows promise in promoting tissue healing

Small-molecule Bcl-2 inhibitors sensitise tumour cells to immune-mediated destruction

The cytotoxic effects of anticancer immune cells are mediated by perforin/granzyme-B, Fas ligand and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), and therefore depend on intact apoptotic responses in target tumour cells. As killing by all three of these mechanisms is blocked by the frequently overexpressed antiapoptotic oncoprotein Bcl-2, we hypothesised that coexposure to a Bcl-2 inhibitor might enhance anticancer immune responses. We evaluated this in U937 lymphoma cells, and A02 melanoma cells, which both show strong Bcl-2 expression. Vα24+ Vβ11+ natural killer T (NKT) cells expanded from peripheral blood of normal donors (n=3) were coincubated with PKH26-labelled U937 cells, and cytotoxicity was determined by flow cytometry after annexin-V-FITC and 7-AAD staining. In all cases, addition of the HA14-1 small-molecule Bcl-2 inhibitor to the cocultures significantly increased apoptosis in the target U937 cells. Using a similar assay, killing of A02 cells by the cytotoxic T-lymphocyte clone 1H3 was shown to be amplified by coexposure to the potent small-molecule Bcl-2 inhibitor ABT-737. Experiments with immune effectors preincubated with concanamycin-A suggested that sensitisation to perforin/granzyme-B may underlie enhanced target-cell killing observed in the presence of Bcl-2 inhibitors. We conclude that immune destruction of malignant cells can be amplified by molecular interventions that overcome Bcl-2-mediated resistance to apoptosis

The Biomechanical Role of Scaffolds in Augmented Rotator Cuff Tendon Repairs

Background Scaffolds continue to be developed and used for rotator cuff repair augmentation; however, the appropriate scaffold material properties and/or surgical application techniques for achieving optimal biomechanical performance remains unknown. The objectives of the study were to simulate a previously validated spring-network model for clinically relevant scenarios to predict: (1) the manner in which changes to components of the repair influence the biomechanical performance of the repair and (2) the percent load carried by the scaffold augmentation component. Materials and methods The models were parametrically varied to simulate clinically relevant scenarios, namely, changes in tendon quality, altered surgical technique(s), and different scaffold designs. The biomechanical performance of the repair constructs and the percent load carried by the scaffold component were evaluated for each of the simulated scenarios. Results The model predicts that the biomechanical performance of a rotator cuff repair can be modestly increased by augmenting the repair with a scaffold that has tendon-like properties. However, engineering a scaffold with supraphysiologic stiffness may not translate into yet stiffer or stronger repairs. Importantly, the mechanical properties of a repair construct appear to be most influenced by the properties of the tendon-to-bone repair. The model suggests that in the clinical setting of a weak tendon-to-bone repair, scaffold augmentation may significantly off-load the repair and largely mitigate the poor construct properties. Conclusions The model suggests that future efforts in the field of rotator cuff repair augmentation may be directed toward strategies that strengthen the tendon-to-bone repair and/or toward engineering scaffolds with tendon-like mechanical properties

Diffusive Release of Photosensitizing Agents (PS) from Novel PVA-Borate Semi-Solid Drug Carriers Through In Vitro Oral Streptococcus mutans Biofilm

Background: Streptococcus mutans, one of the agent of human dental caries, is particularly effective at forming biofilms on the hard tissues of the human oral cavity; the purpose of this study was to investigate and quantify the diffusional release of photosentising agents (PS): methylene blue (MB), toludine blue (TB), rose bengal (RB) and methyl orange (MO) from Polyvinyl alcohol (PVA)-borate semi-solid gels in the presence of in vitro oral Streptococcus mutans biofilm. Methods: S. mutans biofilm growths were ascertained to ensure proper dental plaque formation and were characterized using confocal microscopy. Release profiles for MB, TB, RB and MO-loaded PVA-borate semi-solids in the absence of biofilms were directly compared to their counterparts in the presence of S. mutans biofilms. In addition, their diffusion coefficients and resistances were determined. Results: The confocal imaging results showed that biofilms grown over a 5-day period had a generally uninterrupted film of colonies occupying the entire surface area of growth surface of a nylon mesh support with approximately 60 µm biofilm size. The overall diffusion resistance of all PVA-borate semi-solids in the presence of S. mutans biofilms was about 1.2 times lower than the diffusion resistance for PVAborate semi-solids in the absence of biofilms. The diffusion resistances for all studied PS, indicate that electrostatic forces and molecular size play an important part in controlled and sustained drug release from PVA-borate semi-solids. Conclusions: PVA-borate semi-solids as novel PSs carriers might offer an innovative delivery system in the treatment against Streptococcus mutans