M.D. Ynsa

High Intra-abdominal Pressure Enhances the Penetration and Antitumor Effect of Intraperitoneal Cisplatin on Experimental Peritoneal Carcinomatosis

Objective:To investigate the role of increased intra-abdominal pressure (IAP) on the intratumoral accumulation and the antitumor effect of intraperitoneal cisplatin in rats with advanced peritoneal carcinomatosis. To evaluate the tolerance of IAP in pigs, as it is a large animal with a body size equivalent to humans. Summary Background Data:To investigate if an active convection, driven by a positive IAP, increases cisplatin penetration and antitumor effectiveness in a model of advanced peritoneal carcinomatosis in rats. Experimental Design:BDIX rats with macroscopic peritoneal tumors received cisplatin administered as intravenous injection (IV), conventional intraperitoneal injection (IP), or sustained intraperitoneal injection of cisplatin given in a large volume of solvent for maintaining IAP for 1 hour. Platinum tissue concentration was measured by atomic absorption spectroscopy (AAS), and platinum distribution into the tumor nodules was assessed by the particular-induced x-ray emission (PIXE) method. The antitumor effect was assessed in a survival experiment. The hemodynamic, local, and systemic tolerance of IAP, with or without cisplatin, was evaluated in Large White pigs. Results:The maximum tolerated IAP was 22 mm Hg for 1 hour in nonventilated rats. IAP, in comparison with IV or conventional IP injections, resulted in the increased concentration and depth of diffusion of platinum into diaphragm and peritoneal tumor nodules. Consequently, IAP treatment induced an extended survival of rats treated at an advanced stage of carcinomatosis. In 7 50- to 70-kg ventilated pigs, a 40-mm Hg IAP was well tolerated when maintained stable for 2 hours. Renal failure occurred in pigs receiving a total dose of 200 and 400 mg of cisplatin with IAP, but a dose of 100 mg was well tolerated. Conclusions:Intraperitoneal chemotherapy with increased IAP, in comparison with conventional IP or IV chemotherapy, improved the tumor accumulation and the antitumor effect of cisplatin in rats bearing advanced peritoneal carcinomatosis. In preclinical conditions, the tolerance of sustained IAP was manageable in ventilated pigs.

A novel approach to the identification and quantitative elemental analysis of amyloid deposits—Insights into the pathology of Alzheimer's disease

There is considerable interest in the role of metals such as iron, copper, and zinc in amyloid plaque formation in Alzheimers disease. However to convincingly establish their presence in plaques in vivo, a sensitive technique is required that is both quantitatively accurate and avoids isolation of plaques or staining/fixing brain tissue, since these processes introduce contaminants and redistribute elements within the tissue. Combining the three ion beam techniques of scanning transmission ion microscopy, Rutherford back scattering spectrometry and particle induced X-ray emission in conjunction with a high energy (MeV) proton microprobe we have imaged plaques in freeze-dried unstained brain sections from CRND-8 mice, and simultaneously quantified iron, copper, and zinc. Our results show increased metal concentrations within the amyloid plaques compared with the surrounding tissue: iron (85 ppm compared with 42 ppm), copper (16 ppm compared to 6 ppm), and zinc (87 ppm compared to 34 ppm).

Is there penetration of titania nanoparticles in sunscreens through skin? A comparative electron and ion microscopy study

We report on a comparative study by Transmission Electron Microscopy (HRTEM) and Scanning Transmission Ion Microscopy (STIM) combined with Rutherford Backscattering Spectrometry (RBS) and Particle Induced X-Ray Emission (PIXE) on ultra-thin and thin cross-sections, respectively, of various skin samples (porcine skin, healthy human skin, human skin grafted on a severe combined immuno-deficient mouse model) to which we applied topically various formulations containing titanium dioxide (TiO2) nanoparticles with primary particle sizes in the range from 20–100 nm. Whereas the HRTEM and STIM/PIXE images reveal clear differences – mainly related to the different thickness of the cross-sections – they unambiguously show that penetration of TiO2 nanoparticles is restricted to the topmost 3–5 corneocyte layers of the stratum corneum (SC).

Thick optical waveguides in lithium niobate induced by swift heavy ions (~10 MeV/amu) at ultralow fluences

Heavy mass ions, Kr and Xe, having energies in the approximately 10 MeV/amu range have been used to produce thick planar optical waveguides at the surface of lithium niobate (LiNbO3). The waveguides have a thickness of 40-50 micrometers, depending on ion energy and fluence, smooth profiles and refractive index jumps up to 0.04 (lambda = 633 nm). They propagate ordinary and extraordinary modes with low losses keeping a high nonlinear optical response (SHG) that makes them useful for many applications. Complementary RBS/C data provide consistent values for the partial amorphization and refractive index change at the surface. The proposed method is based on ion-induced damage caused by electronic excitation and essentially differs from the usual implantation technique using light ions (H and He) of MeV energies. It implies the generation of a buried low-index layer (acting as optical barrier), made up of amorphous nanotracks embedded into the crystalline lithium niobate crystal. An effective dielectric medium approach is developed to describe the index profiles of the waveguides. This first test demonstration could be extended to other crystalline materials and could be of great usefulness for mid-infrared applications.

Conditioned bio-interfaces of silicon/porous silicon micro-patterns lead to the chondrogenesis of hMSCs

The interaction between cells and materials is of scientific and technological interest for the development of new biomaterials with improved functional properties. In this work the chondrogenesis (CG) of human mesenchymal stem cells (hMSCs) derived from the bone marrow of healthy donors has been achieved on Si/PSi surfaces after pre-treatment with a conditioned medium derived from hMSCs (CM). The chondrogenic process was analyzed in fixed-cell preparations by immune fluorescence, determining the cellular localization of β-catenin and the transcription factors STAT-5, Runx2 and vitamin D receptor (VDR). In a week of CG on Si/PSi or CM-Si/PSi, β-catenin showed cell–cell contacts priming a preferential chondrogenic process on a PSi surface, in contrast with the preferential proliferation and migration processes observed on hexagonal/triangular micro-designed Si areas. Interestingly, the presence of a CM bio-interface improves this differentiation process with respect to a control PSi surface. The chondroinductive effect was also observed in STAT-5, which was highly expressed and is involved in intracellular signaling of many differentiation receptors related to development and tissue repair. In good agreement with the above results, the co-localization of transcription factors Runx2/VDR at nuclei supports active transcription of chondrogenic genes. Considering these observations, we propose that the combination of a rough PSi surface and the components of the CM-hMSCs bio-interface boosts the chondrogenesis of hMSCs. These findings suggest that the tailoring of Si/PSi scaffolds with appropriate bio-interface combinations improves their therapeutic potential.

Microstructure based optical modeling of ZnO- porous silicon permeated nanocomposites

ZnO composites with porous silicon (PSi) are increasingly used in advanced optical and electronic structures. ZnO/PSi nanocomposites have been prepared by permeating anodized PSi with ZnO sols based on zinc acetate. Upon thermal annealing the ZnO sols form surface wurzite nanocrystals, as indicated by XRD from annealing temperatures of 400 °C. By increasing the annealing up to 800 °C, electron microscopies evidence that ZnO diffuses through the columnar PSi, while void ZnO crystallites decorate the surface. Angular dependent x-ray photoelectron spectra agree with the partial coverage of the PSi surface by disperse ZnO nanocrystals. In depth composition, analyzed using C-resonant backscattering spectroscopy confirms an activation of ZnO diffusion and PSi oxidation at high temperatures. This microstructural information was used to analyse the optical properties through models adapted to critical processing temperatures. A uniaxial anisotropic layer, included to consider columnar PSi, and an evolution of optical coefficients in agreement with thermally induced effects (namely PSi oxidation and ZnO diffusion-transformation) allows to satisfactorily simulate ellipsometric spectra. The results are relevant for the optimization of bifunctional electronic-antireflective ZnO/PSi structures.