Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or ...provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin. The regulatory approved MicronJet600® (MicronJet hereafter) device was used to deliver reporter plasmids (pCMVβ and pEGFP-N1) into viable excised human skin. Exogenous gene expression was subsequently detected at multiple locations that were distant from the injection site but within the confines of the bleb created by the intradermal bolus. The observed levels of gene expression in the tissue are at least comparable to that achieved by the most invasive microneedle application methods e.g. lateral application of a microneedle. Gene expression was predominantly located in the epidermis, although also evident in the papillary dermis. Optical coherence tomography permitted real time visualisation of the sub-surface skin architecture and, unlike a conventional intradermal injection, MicronJet administration of a 50μL bolus appears to create multiple superficial microdisruptions in the papillary dermis and epidermis. These were co-localised with expression of the pCMVβ reporter plasmid. We have therefore shown, for the first time, that a hollow microneedle device can facilitate efficient and reproducible gene expression of exogenous naked pDNA in human skin using volumes that are considered to be standard for intradermal administration, and postulate a hydrodynamic effect as the mechanism of gene delivery.
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Abstract Background Bowel ultrasonography is increasingly used in the detection and follow-up of patients with Crohn's disease, but a limitation to its further diffusion is the lack of ...standardisation of ultrasonography parameters. Aims This study aimed to standardise the most common bowel ultrasonography parameters in order to develop an unequivocal imaging interpretation and to assess bowel ultrasonography reproducibility. Patients Twenty patients with Crohn's disease were examined. Methods Six ultrasonographers (mean bowel ultrasonography experience = 16 years) performed the study. They chose and discussed a common assessment methodology concerning eight ultrasonography parameters: bowel wall thickness, bowel wall pattern, bowel wall blood flow, enlarged mesenteric lymph nodes, mesenteric hypertrophy, abdominal free fluid, and stenosis or fistulae at four preliminary meetings. The day of the study operators were randomised to two rooms where they independently and in turn performed ultrasonography scans. Interobserver agreement was scored by kappa statistics. Results Excellent k values were observed for bowel wall thickness (0.72–1). k Values were poor for bowel wall pattern (−0.22–0.85) and good for bowel wall blood flow (0.53–0.89). The presence of lymph nodes was reproducible (0.56–0.90) except in one case (0.25). Concordance on free fluid was excellent (0.85–1), whereas that on mesenteric hypertrophy was generally poor (0.14–0.69). Agreement was excellent for stenosis (0.81–1) whereas that for fistula was fair in room abscesses (0.31–0.48) and very good in room B (0.87–1). Conclusion Bowel ultrasonography signs used in Crohn's disease can be standardised as most of them showed a fair to good reproducibility. In particular, bowel wall thickness, the most relevant parameter for Crohn's disease detection, showed an excellent reproducibility.
ZrO2-supported La, Mn oxide catalysts with different La, Mn loading (0.7, 2, 4, 6, 12, and 16 wt% as LaMnO3) were prepared by impregnation of tetragonal ZrO2 with equimolar amounts of La and Mn ...citrate precursors and calcination at 1073 K. The catalysts were characterized by X-ray diffraction (XRD), X-ray absorption spectroscopy (XAS), and BET specific surface area determination. The redox properties were tested by temperature-programmed reduction (TPR), and the catalytic tests were carried out for methane combustion at 650–1050 K and for CO oxidation at 350–800 K. XRD revealed the presence of tetragonal zirconia with traces of the monoclinic phase. LaMnO3 perovskite was also detected for loading higher than 6%. XAS and TPR experiments suggested that at high loading small crystallites of LaMnO3, not uniformly spread on the zirconia surface, were formed; while at low loading, La, Mn oxide species interacting with the support, and hard to be structurally defined, prevailed. The catalysis study indicated that the presence of a perovskite-like structure is necessary for the development of highly active sites. Dilute catalysts were in fact poorly active even when considering the activity per gram of La, Mn perovskite-like composition. For methane combustion and CO oxidation, similar trends of the activity as a function of the loading point to a similarity of the active sites for the two reactions on the examined catalytic system.
Abstract Background Capsule endoscopy has a greater diagnostic yield than radiology for detecting subtle inflammatory changes of the small bowel mucosa, but the clinical significance of these ...abnormalities is still uncertain because of the lack of long-term follow-ups. Aim and methods To verify the accuracy of capsule endoscopy in a cohort of patients with suspected Crohn's disease of the small bowel, taking as ‘gold standard’ the final diagnosis made after a long follow-up. From April 2002 to March 2005, we enrolled and examined by capsule endoscopy 27 consecutive patients with abdominal pain and diarrhea lasting more than 3 months and at least one of the following: anaemia, weight loss, fever, extra-intestinal manifestation(s) of inflammatory bowel disease. All patients already had an unremarkable pan-endoscopy, serology for celiac disease and intestinal radiology inconclusive for small bowel abnormality. On the basis of capsule endoscopy findings, patients were distributed in three groups; Group A had severe stricturing lesions requiring surgery; Group B, moderate inflammatory lesions further investigated invasively; Group C, minimal inflammatory changes or normal findings, clinically observed every 3 months (median 21 months, range 15–29). Results Small bowel inflammatory lesions were found in 16 of the 27 patients (diagnostic yield 59%). Three had surgery (Group A) and Crohn's disease was confirmed in two; the remainder had ileal adenocarcinoma in a pathological context of chronic inflammation. Crohn's disease was histologically confirmed in four of the five patients in Group B. Group C comprised 19 patients; Crohn's disease was confirmed in seven out of eight with positive capsule endoscopy, while only one of the patients with normal findings later developed overt ileal Crohn's disease. Sensitivity, specificity, positive and negative likelihood ratio were, respectively, 93%, 84%, 5.8 and 0.08. Assuming a 50% pre-test probability of disease, capsule endoscopy gave a post-test probability of 85%. Conclusions In our selected cohort, capsule endoscopy was highly sensitive in detecting small bowel inflammatory changes, enhancing by nearly 35% the pre-test probability of structural small bowel disease. Focal erythema and luminal debris may limit the specificity of capsule endoscopy.
We present the polarization resolved, angular dependent, optical reflectance properties for single TE mode optical waveguides in contact with a nanostructured gold surface. A substantial angle ...dependent resonant decrease in the TE polarized surface reflectivity is measured which cannot be explained by a simple waveguide coupling due to surface roughness. Rather we show that the resonance is due to the excitation of a coupled waveguide-plasmonic surface mode created by the interaction between the metal nanostructure and the waveguide. A model based on coupled mode theory is introduced in order to explain the experimental data.
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