Photocrosslinked gelatin/chondroitin sulfate/chitosan-based composites with tunable multifunctionality for bone tissue regeneration.

Novel hydrogel-based multifunctional systems prepared utilizing photocrosslinking and freeze-drying processes (PhotoCross/Freeze-dried) dedicated for bone tissue regeneration are presented. Fabricated materials, composed of methacrylated gelatin, chitosan, and chondroitin sulfate, possess interesting features including bioactivity, biocompatibility, as well as antibacterial activity. Importantly, their degradation and swellability might be easily tuned by playing with the biopolymeric content in the photocrosllinked systems. To broaden the potential application and deliver the therapeutic features, mesoporous silica particles functionalized with methacrylate moieties decorated with hydroxyapatite and loaded with the antiosteoporotic drug, alendronate, (MSP-MA-HAp-ALN) were dispersed within the biopolymeric sol and photocrosslinked. It was demonstrated that the obtained composites are characterized by a significantly extended degradation time, ensuring optimal conditions for balancing hybrids removal with the deposition of fresh bone. We have shown that attachment of MSP-MA-HAp-ALN to the polymeric matrix minimizes the initial burst effect and provides a prolonged release of ALN (up to 22 days). Moreover, the biological evaluation in vitro suggested the capability of the resulted systems to promote bone remodeling. Developed materials might potentially serve as scaffolds that after implantation will fill up bone defects of various origin (osteoporosis, tumour resection, accidents) providing the favourable conditions for bone regeneration and supporting the infections' treatment.

Fas/FasL Contributes to HSV-1 Brain Infection and Neuroinflammation.

The Fas/FasL pathway plays a key role in immune homeostasis and immune surveillance. In the central nervous system (CNS) Fas/FasL is involved in axonal outgrowth and adult neurogenesis. However, little is known about the role of the Fas/FasL pathway in herpes encephalitis. In this study, we used a neuropathogenic clinical strain of herpes simplex virus type 1 (HSV-1) to explore infection-induced inflammation and immune responses in the mouse brain and the role of Fas/FasL in antiviral CNS immunity. HSV-1 CNS infection induced the infiltration of Fas- FasL-bearing monocytes and T cells in the brain and also to an up-regulation of Fas and FasL expression on resident astrocytes and microglia within infected sites. Upon infection, Fas- and FasL-deficient mice (lpr and gld) were partially protected from encephalitis with a decreased morbidity and mortality compared to WT mice. Fas/FasL deficiency promoted cell-mediated immunity within the CNS. Fas receptor stimulation abrogated HSV-1 induced activation and inflammatory reactions in microglia from WT mice, while lack of Fas or FasL led to a more pronounced activation of monocytes and microglia and also to an enhanced differentiation of these cells into a pro-inflammatory M1 phenotype. Furthermore, the specific immune system was more efficient in Fas- and FasL-deficient mice with significantly higher numbers of infiltrating HSV-1-specific cytotoxic T cells in the brain. Our data indicate that the Fas/FasL pathway leads to excessive neuroinflammation during HSV-1 infection, which is associated with a diminished anti-viral response and an excessive neuroinflammation.

Catalytic Performance of Spherical MCM-41 Modified with Copper and Iron as Catalysts of NH3-SCR Process.

Spherical MCM-41 with various copper and iron loadings was prepared by surfactant directed co-condensation method. The obtained samples were characterized with respect to their structure (X-ray diffraction, XRD), texture (N2 sorption), morphology (scanning electron microscopy, SEM), chemical composition (inductively coupled plasma optical emission spectrometry, ICP-OES), surface acidity (temperature programmed desorption of ammonia, NH3-TPD), form, and aggregation of iron and copper species (diffuse reflectance UV-Vis spectroscopy, UV-Vis DRS) as well as their reducibility (temperature programmed reduction with hydrogen, H2-TPR). The spherical MCM-41 samples modified with transition metals were tested as catalysts of selective catalytic reduction of NO with ammonia (NH3-SCR). Copper containing catalysts presented high catalytic activity at low-temperature NH3-SCR with a very high selectivity to nitrogen, which is desired reaction products. Similar results were obtained for iron containing catalysts, however in this case the loadings and forms of iron incorporated into silica samples very strongly influenced catalytic performance of the studied samples. The efficiency of the NH3-SCR process at higher temperatures was significantly limited by the side reaction of direct ammonia oxidation. The reactivity of ammonia molecules chemisorbed on the catalysts surface in NO reduction (NH3-SCR) and their selective oxidation (NH3-SCO) was verified by temperature-programmed surface reactions.

Nitric Oxide Influences HSV-1-Induced Neuroinflammation.

Herpes simplex virus type 1 (HSV-1) has the ability to replicate in neurons and glial cells and to produce encephalitis leading to neurodegeneration. Accumulated evidence suggests that nitric oxide (NO) is a key molecule in the pathogenesis of neurotropic virus infections. NO can exert both cytoprotective as well as cytotoxic effects in the central nervous system (CNS) depending on its concentration, time course exposure, and site of action. In this study, we used an in vitro model of HSV-1-infected primary neuronal and mixed glial cultures as well as an intranasal model of HSV-1 in BALB/c mice to elucidate the role of NO and nonapoptotic Fas signalling in neuroinflammation and neurodegeneration. We found that low, nontoxic concentration of NO decreased HSV-1 replication in neuronal cultures together with production of IFN-alpha and proinflammatory chemokines. However, in HSV-1-infected glial cultures, low concentrations of NO supported virus replication and production of IFN-alpha and proinflammatory chemokines. HSV-1-infected microglia downregulated Fas expression and upregulated its ligand, FasL. Fas signalling led to production of proinflammatory cytokines and chemokines as well as induced iNOS in uninfected bystander glial cells. On the contrary, NO reduced production of IFN-alpha and CXCL10 through nonapoptotic Fas signalling in HSV-1-infected neuronal cultures. Here, we also observed colocalization of NO production with the accumulation of ß-amyloid peptide in HSV-1-infected neurons both in vitro and in vivo. Low levels of the NO donor increased accumulation of ß-amyloid in uninfected primary neuronal cultures, while the NO inhibitor decreased its accumulation in HSV-1-infected neuronal cultures. This study shows for the first time the existence of a link between NO and Fas signalling during HSV-1-induced neuroinflammation and neurodegeneration.

Antiviral Activity of Tannic Acid Modified Silver Nanoparticles: Potential to Activate Immune Response in Herpes Genitalis.

(1) Background: Tannic acid is a plant-derived polyphenol showing antiviral activity mainly because of an interference with the viral adsorption. In this work, we tested whether the modification of silver nanoparticles with tannic acid (TA-AgNPs) can provide a microbicide with additional adjuvant properties to treat genital herpes infection. (2) Methods: The mouse model of the vaginal herpes simplex virus 2 (HSV-2) infection was used to test immune responses after treatment of the primary infection with TA-AgNPs, and later, after a re-challenge with the virus. (3) Results: The mice treated intravaginally with TA-AgNPs showed better clinical scores and lower virus titers in the vaginal tissues soon after treatment. Following a re-challenge, the vaginal tissues treated with TA-AgNPs showed a significant increase in the percentages of IFN-gamma+ CD8+ T-cells, activated B cells, and plasma cells, while the spleens contained significantly higher percentages of IFN-gamma+ NK cells and effector-memory CD8+ T cells in comparison to NaCl-treated group. TA-AgNPs-treated animals also showed significantly better titers of anti-HSV-2 neutralization antibodies in sera; and (4) Conclusions: Our findings suggest that TA-AgNPs sized 33 nm can be an effective anti-viral microbicide to be applied upon the mucosal tissues with additional adjuvant properties enhancing an anti-HSV-2 immune response following secondary challenge.

Ultra high-speed swept source OCT imaging of the anterior segment of human eye at 200 kHz with adjustable imaging range.

We present an application of in vivo anterior segment imaging of the human eye with an ultrahigh speed swept source OCT instrument. For this purpose, a dedicated OCT system was designed and constructed. This instrument enables axial zooming by automatic reconfiguration of spectral sweep range; an enhanced imaging range mode enables imaging of the entire anterior segment while a high axial resolution mode provides detailed morphological information of the chamber angle and the cornea. The speed of 200,000 lines/s enables high sampling density in three-dimensional imaging of the entire cornea in 250 ms promising future applications of OCT for optical corneal topography, pachymetry and elevation maps. The results of a preliminary quantitative corneal analysis based on OCT data free form motion artifacts are presented. Additionally, a volumetric and real time reconstruction of dynamic processes, like pupillary reaction to light stimulus or blink-induced contact lens movements are demonstrated.

Analysis of the outer retina reconstructed by high-resolution, three-dimensional spectral domain optical coherence tomography.

BACKGROUND AND OBJECTIVE: A retrospective cross-sectional study was conducted to demonstrate an analysis of an outer retinal layer reconstructed by the three-dimensional and high-speed spectral domain optical coherence tomography (SD-OCT) instrument. PATIENTS AND METHODS: New measurement protocols for SD-OCT and methods of analysis and visualization of the individual segmented retinal layer reconstructed by SD-OCT were proposed. Three contour maps representing mutual distances between the basal part of the retinal pigment epithelium, the junction between the inner and outer segments of photoreceptors, and a reference contour representing the shape of a healthy retina were introduced. RESULTS: The analysis of the outer retina was performed on pathological eyes. Three cases of central serous chorioretinopathy, age-related macular degeneration, and acute zonal occult outer retinopathy are demonstrated. CONCLUSION: Three contour maps reconstructed for clinical cases demonstrate high variability of observed patterns depending on analyzed pathology. The authors believe this can help to present OCT data simultaneously in a more comprehensive and convenient way to assist in everyday clinical diagnosis.

Fuchs' endothelial dystrophy in 830-nm spectral domain optical coherence tomography.

This article presents for the first time the potential of 830-nm spectral domain optical coherence tomography (SD-OCT) in the evaluation of Fuchs' endothelial dystrophy. SD-OCT is an imaging technique that can be used for in vivo cross-sectional corneal visualization. The important features of SD-OCT instruments include improved sensitivity and short acquisition time, which improves the quality of the tomograms compared with conventional time domain OCT. Tomograms of the corneas of three patients in different stages of Fuchs' endothelial dystrophy are presented. The authors conclude that 830-nm SD-OCT provides clinically valuable cross-sectional assessment of pathomorphological changes in Fuchs' endothelial dystrophy in vivo.

In vivo imaging of posterior capsule opacification using Spectral Optical Coherence Tomography.

Three years after uneventful extracapsular cataract extraction with implantation of a poly(methyl methacrylate) (PMMA) intraocular lens (IOL) (MZ60BD, Alcon) in a 74-year-old man, the anterior segment of the right eye was photographed with a Canon EOS 300D digital camera and examined with a slitlamp and a prototype spectral optical coherence tomography (SOCT) instrument. Subsequently, a neodymium:YAG laser posterior capsulotomy was performed, followed by another examination. The quality of the SOCT images was adequate for detailed cross-sectional evaluation of the IOL, posterior capsule opacification (PCO), and morphological changes after laser capsulotomy. En face contour maps of PCO distribution were created from 3-dimensional SOCT data. The results presented indicate future applicability of SOCT technology in evaluating modern IOL designs and investigating the process of PCO formation.

[Renal osteodystrophy as a cause of false positive result of whole body scintigraphy in a patient with differentiated thyroid cancer]. / Osteodystrofia nerkowa przyczyna falszywie dodatniej scyntygrafii calego ciala u chorego ze zróznicowanym rakiem tarczycy.

We demonstrated the case of coexistence of secondary hyperparathyroidism in the course of irreversible renal failure and differentiated thyroid carcinoma diagnosed at the time of parathyroidectomy. Changes in skeletal system caused by secondary hyperparathyroidism resulted in false positive result of whole body scintigraphy and required differentiation with bone metastases of thyroid cancer. Therefore, the diagnostic tests of thyroid gland are necessary before parathyroidectomy in patients with secondary hyperparathyroidism.

[Application of spectral optical coherent tomography (SOCT) in ophthalmology]. / Zastosowanie spektralnej tomografii optycznej (SOCT) w okulistyce.

The article describes spectral optical coherent tomography (SOCT) constructed by Medical Physics Group, Faculty of Physics, Astronomy and Informatics at Nicholas Copernicus University in Torun (Poland). It presents the physical bases for the functioning of the constructed device and includes pictures of optical sections of various elements of the eyeball: an optic disc and the region of central fovea, a cornea and angle structures (trabecular meshwork). The article also discusses potential application of SOCT in ophthalmic diagnosis of anterior and posterior segments of the eye.