Pharmacological Activity of Ibuprofen Release from Measoporous Silica

Novel drug delivery systems (DDS) to improve the pharmacokinetic profile of hydrophobic drugs following oral administration are an area of keen interest in drug research. An ideal DDS should not adversely affect drug activity, be capable of delivering a therapeutic dose of drug, and allow homogenous drug loading and drug release. Mesoporous silica has been proposed for this application, with ibuprofen employed as the model drug. It was hypothesised that mesoporous silica MCM-41 is capable of delivering a pharmacologically therapeutic dose of ibuprofen. Ibuprofen-loaded MCM-41 can be prepared reproducibly at a drug to carrier ratio of 30% (wt/wt). The release profile was seen to be 90% within 2 h. Initial assessment of COX-1 inhibitory activity suggests the absence of adverse effects attributable to drug-carrier interaction. The results of this study provide further evidence in support of the proposed use of mesoporous silica in drug delivery.

Millimeter-wave and submillimeter-wave imaging for security and surveillance

Passive equipments operating in the 30-300 GHZ (millimeter wave) band are compared to those in the 300 GHz-3 THz (submillimeter band). Equipments operating in the submillimeter band can measure distance and also spectral information and have been used to address new opportunities in security. Solid state spectral information is available in the submillimeter region making it possible to identify materials, whereas in millimeter region bulk optical properties determine the image contrast. The optical properties in the region from 30 GHz to 3 THz are discussed for some typical inorganic and organic solids. in the millimeter-wave region of the spectrum, obscurants such as poor weather, dust, and smoke can be penetrated and useful imagery generated for surveillance. in the 30 GHZ-3 THZ region dielectrics such as plastic and cloth are also transparent and the detection of contraband hidden under clothing is possible. A passive millimeter-wave imaging concept based on a folded Schmidt camera has been developed and applied to poor weather navigation and security. The optical design uses a rotating mirror and is folded using polarization techniques. The design is very well corrected over a wide field of view making it ideal for surveillance, and security. This produces a relatively compact imager which minimizes the receiver count.

Relative biological effectiveness (RBE) and out-of-field cell survival responses to passive scattering and pencil beam scanning proton beam deliveries

The relative biological effectiveness (RBE) of passive scattered (PS) and pencil beam scanned (PBS) proton beam delivery techniques for uniform beam configurations was determined by clonogenic survival. The radiobiological impact of modulated beam configurations on cell survival occurring in- or out-of-field for both delivery techniques was determined with intercellular communication intact or physically inhibited. Cell survival responses were compared to those observed using a 6 MV photon beam produced with a linear accelerator. DU-145 cells showed no significant difference in survival response to proton beams delivered by PS and PBS or 6 MV photons taking into account a RBE of 1.1 for protons at the centre of the spread out Bragg peak. Significant out-of-field effects similar to those observed for 6 MV photons were observed for both PS and PBS proton deliveries with cell survival decreasing to 50-60% survival for scattered doses of 0.05 and 0.03 Gy for passive scattered and pencil beam scanned beams respectively. The observed out-of-field responses were shown to be dependent on intercellular communication between the in-and out-of-field cell populations. These data demonstrate, for the first time, a similar RBE between passive and actively scanned proton beams and confirm that out-of-field effects may be important determinants of cell survival following exposure to modulated photon and proton fields

The shifting engines of medicalization

Social scientists and other analysts have written about medicalization since at least the 1970s. Most of these studies depict the medical profession, interprofessional or organizational contests, or social movements and interest groups as the prime movers toward medicalization. This article contends that changes in medicine in the past two decades are altering the medicalization process. Using several case examples, I argue that three major changes in medical knowledge and organization have engendered an important shift in the engines that drive medicalization: biotechnology (especially the pharmaceutical industry and genetics), consumers, and managed care. Doctors are still gatekeepers for medical treatment, but their role has become more subordinate in the expansion or contraction of medicalization. Medicalization is now more driven by commercial and market interests than by professional claims-makers. The definitional center of medicalization remains constant, but the availability of new pharmaceutical and potential genetic treatments are increasingly drivers for new medical categories. This requires a shift in the sociological focus examining medicalization for the twenty-first century.

A mirage of genes

This paper examines the structure of popular conceptions of the new genetics, and assesses why genetics has been so readily accepted in medicine and in the public discourse. Adapting Rene Dubos' classic analysis, Mirage of Health, we examine the new genetics by comparing it to Dubos' analysis of the structure and limits of germ theory. Germ theory focuses on the internal rather than the external environment, emphasises a doctrine of specific aetiology, and adopts the metaphor of the body as a machine. The germ theory model narrowed our vision about disease aetiology, proved misleading in some cases, yet remained the basis for clinical medical models of disease. In recent years, genetics has moved to the cutting edge of medical research and thinking about disease and behaviour. The structure of popular conceptions of the new genetics shows remarkable parallels with germ theory. This has eased the acceptance of genetics but simultaneously raises questions about these genetic explanations. An appearance and allure of specificity privileges genetic explanations in the public discourse; on examination, this specificity may prove to be a mirage.

The NAD(P)H : quinone oxidoreductase IC609T polymorphism modifies the risk of Barrett esophagus and esophageal adenocarcinoma

Purpose: The role of genetic susceptibility to esophageal adenocarcinorna and its precursor lesion Barrett esophagus has not been fully elucidated. This study investigated the effect of polymorphisms in the manganese superoxide dismutase (MnSOD) and NAD(P)H:quinone oxicloreductase 1 (NQO1) genes in modulating the risk of developing Barrett esophagus or esophageal adenocarcinoma. Methods: A total of 584 patients (146 esophagitis, 200 Barrett esophagus, 144 esophageal adenocarcinoma, and 94 controls) were genotyped for the MnSOD C14T and NQO1 C609T polymorphisms using polymerase chain reaction and restriction fragment length polymorphism analysis. Results: The NQO1 TT genotype was less common in Barrett esophagus (2.0%) and esophageal adenocarcinoma (1.4%) patients, compared with both esophagitis patients (7.6%) and controls (5.4%). After adjustment for sex, age, body mass index, reflux symptoms, and smoking status, patients with the homozygous TT genotype had a 4.5-fold decreased risk of developing Barrett esophagus (odds ratio = 0.22, 95% confidence interval = 0.07-0.76, P = 0.01) and a 6.2-fold decreased risk of esophageal adenocarcinorna (odds ratio = 0.16, 95% confidence intervals = 0.03-0.94, P = 0.04) compared with individuals with the TC and CC genotypes. No significant differences between groups were observed for the MnSOD polymorphism (P = 0.289). Conclusions: Overall, the results of this study suggest that the NQO1 TT genotype may offer protection from reflux complications such as Barrett esophagus and esophageal adenocarcinoma.

Optimization of image quality and dose for Varian aS500 electronic portal imaging devices (EPIDs)

This study was carried out to investigate whether the electronic portal imaging (EPI) acquisition process could be optimized, and as a result tolerance and action levels be set for the PIPSPro QC-3V phantom image quality assessment. The aim of the optimization process was to reduce the dose delivered to the patient while maintaining a clinically acceptable image quality. This is of interest when images are acquired in addition to the planned patient treatment, rather than images being acquired using the treatment field during a patient's treatment. A series of phantoms were used to assess image quality for different acquisition settings relative to the baseline values obtained following acceptance testing. Eight Varian aS500 EPID systems on four matched Varian 600C/D linacs and four matched Varian 2100C/D linacs were compared for consistency of performance and images were acquired at the four main orthogonal gantry angles. Images were acquired using a 6 MV beam operating at 100 MU min(-1) and the low-dose acquisition mode. Doses used in the comparison were measured using a Farmer ionization chamber placed at d(max) in solid water. The results demonstrated that the number of reset frames did not have any influence on the image contrast, but the number of frame averages did. The expected increase in noise with corresponding decrease in contrast was also observed when reducing the number of frame averages. The optimal settings for the low-dose acquisition mode with respect to image quality and dose were found to be one reset frame and three frame averages. All patients at the Northern Ireland Cancer Centre are now imaged using one reset frame and three frame averages in the 6 MV 100 MU min(-1) low-dose acquisition mode. Routine EPID QC contrast tolerance (+/-10) and action (+/-20) levels using the PIPSPro phantom based around expected values of 190 (Varian 600C/D) and 225 (Varian 2100C/D) have been introduced. The dose at dmax from electronic portal imaging has been reduced by approximately 28%, and while the image quality has been reduced, the images produced are still clinically acceptable.

A low-cost solution for the restoration of femoral head centre during total hip arthroplasty

Restoration of joint centre during total hip arthroplasty is critical. While computer-aided navigation can improve accuracy during total hip arthroplasty, its expense makes it inaccessible to the majority of surgeons. This article evaluates the use, in the laboratory, of a calliper with a simple computer application to measure changes in femoral head centres during total hip arthroplasty. The computer application was designed using Microsoft Excel and used calliper measurements taken pre- and post-femoral head resection to predict the change in head centre in terms of offset and vertical height between the femoral head and newly inserted prosthesis. Its accuracy was assessed using a coordinate measuring machine to compare changes in preoperative and post-operative head centre when simulating stem insertion on 10 sawbone femurs. A femoral stem with a modular neck was used, which meant nine possible head centre configurations were available for each femur, giving 90 results. The results show that using this technique during a simulated total hip arthroplasty, it was possible to restore femoral head centre to within 6?mm for offset (mean 1.67?±?1.16?mm) and vertical height (mean 2.14?±?1.51?mm). It is intended that this low-cost technique be extended to inform the surgeon of a best-fit solution in terms of neck length and neck type for a specific prosthesis.

Octavius 4D characterization for flattened and flattening filter free rotational deliveries

Purpose: In this study the Octavius detector 729 ionization chamber (IC) array with the Octavius 4D phantom was characterized for flattening filter (FF) and flattening filter free (FFF) static and rotational beams. The device was assessed for verification with FF and FFF RapidArc treatment plans.

Methods: The response of the detectors to field size, dose linearity, and dose rate were assessed for 6 MV FF beams and also 6 and 10 MV FFF beams. Dosimetric and mechanical accuracy of the detector array within the Octavius 4D rotational phantom was evaluated against measurements made using semiflex and pinpoint ionization chambers, and radiochromic film. Verification FF and FFF RapidArc plans were assessed using a gamma function with 3%/3 mm tolerances and 2%/2 mm tolerances and further analysis of these plans was undertaken using film and a second detector array with higher spatial resolution.

Results: A warm-up dose of >6 Gy was required for detector stability. Dose-rate measurements were stable across a range from 0.26 to 15 Gy/min and dose response was linear, although the device overestimated small doses compared with pinpoint ionization chamber measurements. Output factors agreed with ionization chamber measurements to within 0.6% for square fields of side between 3 and 25 cm and within 1.2% for 2 x 2 cm(2) fields. The Octavius 4D phantom was found to be consistent with measurements made with radiochromic film, where the gantry angle was found to be within 0.4. of that expected during rotational deliveries. RapidArc FF and FFF beams were found to have an accuracy of >97.9% and >90% of pixels passing 3%/3 mm and 2%/2 mm, respectively. Detector spatial resolution was observed to be a factor in determining the accurate delivery of each plan, particularly at steep dose gradients. This was confirmed using data from a second detector array with higher spatial resolution and with radiochromic film.

Conclusions: The Octavius 4D phantom with associated Octavius detector 729 ionization chamber array is a dosimetrically and mechanically stable device for pretreatment verification of FF and FFF RapidArc treatments. Further improvements may be possible through use of a detector array with higher spatial resolution (detector size and/or detector spacing). (C) 2013 American Association of Physicists in Medicine.

Implementation of phantom-less IMRT delivery verification using Varian DynaLog files and R/V output

This study aims to evaluate the use of Varian radiotherapy dynamic treatment log (DynaLog) files to verify IMRT plan delivery as part of a routine quality assurance procedure. Delivery accuracy in terms of machine performance was quantified by multileaf collimator (MLC) position errors and fluence delivery accuracy for patients receiving intensity modulated radiation therapy (IMRT) treatment. The relationship between machine performance and plan complexity, quantified by the modulation complexity score (MCS) was also investigated. Actual MLC positions and delivered fraction of monitor units (MU), recorded every 50 ms during IMRT delivery, were extracted from the DynaLog files. The planned MLC positions and fractional MU were taken from the record and verify system MLC control file. Planned and delivered beam data were compared to determine leaf position errors with and without the overshoot effect. Analysis was also performed on planned and actual fluence maps reconstructed from the MLC control file and delivered treatment log files respectively. This analysis was performed for all treatment fractions for 5 prostate, 5 prostate and pelvic node (PPN) and 5 head and neck (H&N) IMRT plans, totalling 82 IMRT fields in ∼5500 DynaLog files. The root mean square (RMS) leaf position errors without the overshoot effect were 0.09, 0.26, 0.19 mm for the prostate, PPN and H&N plans respectively, which increased to 0.30, 0.39 and 0.30 mm when the overshoot effect was considered. Average errors were not affected by the overshoot effect and were 0.05, 0.13 and 0.17 mm for prostate, PPN and H&N plans respectively. The percentage of pixels passing fluence map gamma analysis at 3%/3 mm was 99.94 ± 0.25%, which reduced to 91.62 ± 11.39% at 1%/1 mm criterion. Leaf position errors, but not gamma passing rate, were directly related to plan complexity as determined by the MCS. Site specific confidence intervals for average leaf position errors were set at -0.03-0.12 mm for prostate and -0.02-0.28 mm for more complex PPN and H&N plans. For all treatment sites confidence intervals for RMS errors with the overshoot was set at 0-0.50 mm and for the percentage of pixels passing a gamma analysis at 1%/1 mm a confidence interval of 68.83% was set also for all treatment sites. This work demonstrates the successful implementation of treatment log files to validate IMRT deliveries and how dynamic log files can diagnose delivery errors not possible with phantom based QC. Machine performance was found to be directly related to plan complexity but this is not the dominant determinant of delivery accuracy.

Dose, dose-rate and field size effects on cell survival following exposure to non-uniform radiation fields

For the delivery of intensity-modulated radiation therapy (IMRT), highly modulated fields are used to achieve dose conformity across a target tumour volume. Recent in vitro evidence has demonstrated significant alterations in cell survival occurring out-of-field which cannot be accounted for on the basis of scattered dose. The radiobiological effect of area, dose and dose-rate on out-of-field cell survival responses following exposure to intensity-modulated radiation fields is presented in this study. Cell survival was determined by clonogenic assay in human prostate cancer (DU-145) and primary fibroblast (AG0-1522) cells following exposure to different modulated field configurations delivered using a X-Rad 225 kVp x-ray source. Uniform survival responses were compared to in- and out-of-field responses in which 25-99% of the cell population was shielded. Dose delivered to the out-of-field region was varied from 1.6-37.2% of that delivered to the in-field region using different levels of brass shielding. Dose rate effects were determined for 0.2-4 Gy min⁻¹ for uniform and modulated exposures with no effect seen in- or out-of-field. Survival responses showed little dependence on dose rate and area in- and out-of-field with a trend towards increased survival with decreased in-field area. Out-of-field survival responses were shown to scale in proportion to dose delivered to the in-field region and also local dose delivered out-of-field. Mathematical modelling of these findings has shown survival response to be highly dependent on dose delivered in- and out-of-field but not on area or dose rate. These data provide further insight into the radiobiological parameters impacting on cell survival following exposure to modulated irradiation fields highlighting the need for refinement of existing radiobiological models to incorporate non-targeted effects and modulated dose distributions.

Morphology and compression behaviour of biodegradable scaffolds produced by the sintering process

Porous poly(L-lactic acid) (PLA) scaffolds of 85 per cent and 90 per cent porosity are prepared using polymer sintering and porogen leaching method. Different weight fractions of 10 per cent, 30 per cent, and 50 per cent of hydroxyapatite (HA) are added to the PLA to control the acidity and degradation rate. The three-dimensional (3D) morphology and surface porosity are tested using micro-computer tomography (micro-CT), optical microscopy, and scanning electron microscopy (SEM). Results indicate that the surface porosity does not change on the addition of HA. The micro-CT examinations show a slight decrease in the pore size and increase in the wall thickness accompanied by reduced anisotropy for the scaffolds containing HA. Scanning electron micrographs show detectable interconnected pores for the scaffold with pure PLA. Addition of the HA results in agglomeration of the HA particles and reduced leaching of the porogen. Compression tests of the scaffold identify three stages in the stress-strain curve. The addition of HA results in a reduction in the modulus of the scaffold at the first stage of elastic bending of the wall, but this is reversed for the second and third stages of collapse of the wall and densification in the compression tests. In the scaffolds with 85 per cent porosity, the addition of a high percentage of HA could result in 70 per cent decrease in stiffness in the first stage, 200 per cent increase in stiffness in the second stage, and 20 per cent increase in stiffness in the third stage. The results of these tests are compared with the Gibson cellular material model that is proposed for prediction of the behaviour of cellular material under compression. The pH and molecular weight changes are tracked for the scaffolds within a period of 35 days. The addition of HA keeps the pH in the alkaline region, which results in higher rate of degradation at an early period of observation, followed by a reduced rate of degradation later in the process. The final molecular weight is higher for the scaffolds with HA than for scaffolds of pure PLA. The manufactured scaffolds offer acceptable properties in terms of the pore size range and interconnectivity of the pores and porosity for non-load-bearing bone graft substitute; however, improvement to the mixing of the phases of PLA and HA is required to achieve better integrity of the composite scaffolds. © 2008 IMechE.

Analysis of the compressive behaviour of the three-dimensional printed porous titanium for dental implants using a modified cellular solid model

A set of cylindrical porous titanium test samples were produced using the three-dimensional printing and sintering method with samples sintered at 900 °C, 1000 °C, 1100 °C, 1200 °C or 1300 °C. Following compression testing, it was apparent that the stress-strain curves were similar in shape to the curves that represent cellular solids. This is despite a relative density twice as high as what is considered the threshold for defining a cellular solid. As final sintering temperature increased, the compressive behaviour developed from being elastic-brittle to elastic-plastic and while Young's modulus remained fairly constant in the region of 1.5 GPa, there was a corresponding increase in 0.2% proof stress of approximately 40-80 MPa. The cellular solid model consists of two equations that predict Young's modulus and yield or proof stress. By fitting to experimental data and consideration of porous morphology, appropriate changes to the geometry constants allow modification of the current models to predict with better accuracy the behaviour of porous materials with higher relative densities (lower porosity).