Influence of metabolic syndrome on post-stroke outcome,angiogenesis and vascular function in old rats determined by dynamic contrast enhanced MRI

Stroke affects primarily aged and co-morbid people, aspects not properly considered to date. Since angiogenesis/vasculogenesis are key processes for stroke recovery, we purposed to determine how different co-morbidities affect the outcome and angiogenesis/vasculogenesis, using a rodent model of metabolic syndrome, and by dynamic enhanced-contrast imaging (DCE-MRI) to assess its non-invasive potential to determine these processes. Twenty/twenty-two month-old corpulent (JCR:LA-Cp/Cp), a model of metabolic syndrome and lean rats were used. After inducing the experimental ischemia by transient MCAO, angiogenesis was analyzed by histology, vasculogenesis by determination of endothelial progenitor cells in peripheral blood by flow cytometry and evaluating their pro-angiogenic properties in culture and the vascular function by DCE-MRI at 3, 7 and 28 days after tMCAO. Our results show an increased infarct volume, BBB damage and an impaired outcome in corpulent rats compared with their lean counterparts. Corpulent rats also displayed worse post-stroke angiogenesis/vasculogenesis, outcome that translated in an impaired vascular function determined by DCE-MRI. These data confirm that outcome and angiogenesis/vasculogenesis induced by stroke in old rats are negatively affected by the co-morbidities present in the corpulent genotype and also that DCE-MRI might be a technique useful for the non-invasive evaluation of vascular function and angiogenesis processes.     

Differential Interleukin-8 thresholds for chemotaxis and netosis in human neutrophils

In humans, IL-8 (CXCL8) is a key chemokine for chemotaxis of polymorphonuclear leukocytes and monocytes/macrophages when acting on CXCR1 and CXCR2. CXCL8 activity on neutrophils includes chemotaxis and eliciting the extrusion of neutrophil extracellular traps (NETs). In this study, we show that concentrations of IL-8 that induce NETosis surpass in at least one order of magnitude those required to elicit chemoattraction in human neutrophils. IL-8-induced NETosis was less dependent on G-proteins than migration, while extracellular Ca⁺² chelation similarly inhibited both processes. Reactive oxygen species (ROS) were more important for NETosis than for chemotaxis as evidenced by neutralization with N-acetyl -cysteine. Interestingly, selective blockade with anti-CXCR1 mAb inhibited NETosis much more readily than chemotaxis, while pharmacological inhibition of both CXCR1 and CXCR2, or selective inhibition for CXCR2 alone, similarly inhibited both functions. Together, these results propose a model according to which low concentrations of IL-8 in a gradient attract neutrophils to the inflammatory foci, while high receptor-saturating concentrations of IL-8 give rise to NETosis once leukocytes reach the core of the inflammatory insult.     

How to report the antinuclear antibodies (anti-cell antibodies) test on HEp-2 cells: guidelines from the ICAP initiative

Immunologic Research - Results of the anti-nuclear antibodies-indirect immunofluorescence assay (anti-cell antibodies test) on HEp-2 cell substrates should be communicated to clinicians in a...     

Computed tomography and histological evaluation of xenogenic and biomimetic bone grafts in three-wall alveolar defects in minipigs

Objectives

This study aimed to compare the performance of a xenograft (XG) and a biomimetic synthetic graft (SG) in three-wall alveolar defects in minipigs by means of 3D computerised tomography and histology.

Materials and methods

Eight minipigs were used. A total of eight defects were created in the jaw of each animal, three of which were grafted with XGs, three with SGs, and two were left empty as a negative control. The allocation of the different grafts was randomised. Four animals were euthanised at 6 weeks and four at 12 weeks. The grafted volume was then measured by spiral computed tomography to assess volume preservation. Additionally, a histological analysis was performed in undecalcified samples by backscattered scanning electron microscopy and optical microscopy after Masson’s trichrome staining.

Results

A linear mixed-effects model was applied considering four fixed factors (bone graft type, regeneration time, anatomic position, and maxilla/mandible) and one random factor (animal). The SG exhibited significantly larger grafted volume (19%) than the XG. The anterior sites preserved better the grafted volume than the posterior ones. Finally, regeneration time had a positive effect on the grafted volume. Histological observations revealed excellent osseointegration and osteoconductive properties for both biomaterials. Some concavities found in the spheroidal morphologies of SGs were associated with osteoclastic resorption.

Conclusions

Both biomaterials met the requirements for bone grafting, i.e. biocompatibility, osseointegration, and osteoconduction. Granule morphology was identified as an important factor to ensure a good volume preservation.

Clinical relevance

Whereas both biomaterials showed excellent osteoconduction, SGs resulted in better volume preservation.

     

Significance of implant design on the efficacy of different peri-implantitis decontamination protocols

Clinical Oral Investigations - To assess the efficacy of three mechanical decontamination methods in four types of commercially available implants. Ninety-six implants of four commercial brands...     

Patient-specific simulations of stenting procedures in coronary bifurcations: Two clinical cases

Computational simulations of stenting procedures in idealized geometries can only provide general guidelines and their use in the patient-specific planning of percutaneous treatments is inadequate. Conversely, image-based patient-specific tools that are able to realistically simulate different interventional options might facilitate clinical decision-making and provide useful insights on the treatment for each individual patient.The aim of this work is the implementation of a patient-specific model that uses image-based reconstructions of coronary bifurcations and is able to replicate real stenting procedures following clinical indications. Two clinical cases are investigated focusing the attention on the open problems of coronary bifurcations and their main treatment, the provisional side branch approach. Image-based reconstructions are created combining the information from conventional coronary angiography and computed tomography angiography while structural finite element models are implemented to replicate the real procedure performed in the patients.First, numerical results show the biomechanical influence of stents deployment in the coronary bifurcations during and after the procedures. In particular, the straightening of the arterial wall and the influence of two overlapping stents on stress fields are investigated here. Results show that a sensible decrease of the vessel tortuosity occurs after stent implantation and that overlapping devices result in an increased stress state of both the artery and the stents. Lastly, the comparison between numerical and image-based post-stenting configurations proved the reliability of such models while replicating stent deployment in coronary arteries.     

Assessment of in vitro cytotoxicity of imidazole ionic liquids and inclusion in targeted drug carriers containing violacein

Violacein (Viol) is a pigment produced by several Gram-negative bacteria with many bioactivities, such as anticancer, virucide, and antiparasitic. However, violacein is insoluble under physiological conditions preventing its potential therapeutic uses. Surface-active ionic liquids (SAILs) based on the cation 1-alkylimidazolium ([C_nHim]) with n = 10 to 16 alkyl carbon side chain lengths and acetate, bromide, methanesulfonate (S) or trifluoroacetate (F) as counterions were synthesized and screened to dissolve Viol in micellar aqueous media and for toxicological studies on the human lung carcinoma A549 cell line. Screening allowed the selection of 1.5 × 10⁻³% (w/v) [C₁₆Him]-S because it combines low cytotoxicity with 71.5% cell viability and good interaction with 95.2% of the violacein kept in micellar solution for at least 48 h. [Viol-([C₁₆Him]-S)] complex was used to develop an efficient hybrid solid lipid nanoparticle (SLN) carrier based on myristyl myristate and poloxamer 188 and tailored with folate to target cancer cells. Cellular SLN uptake was evaluated with fluorescent DiOC₁₈ on A549, HCT-116, and HeLa cell lines expressing or not the folate receptor. The results showed fivefold incorporation of Viol nanoparticles in HCT-116 and HeLa cell cultures, displaying a high level of folate receptor. Biophysical characterization of the hybrid solid lipid carrier containing Viol was performed by dynamic light scattering, Fourier transform infrared, X-ray diffraction and X-ray photoelectron spectroscopies, and by transmission electron and cryo-transmission microscopies.

Violacein (Viol) is a pigment produced by several Gram-negative bacteria with many bioactivities, such as anticancer, virucide, and antiparasitic.     

Solid state interdigitated Sb2S3 based TiO2 nanotube solar cells

TiO₂ nanotubes generated by anodization of metallic titanium sputter-coated on indium tin oxide (ITO) substrates are used as a conductive scaffold for all solid-state Sb₂S₃-sensitized extremely thin absorber (ETA) solar cells. A blocking layer of TiO₂ placed between Ti and ITO in combination with optimized Ti deposition and anodization conditions enables the formation of crack-free layers of straight, cylindrical TiO₂ nanotubes of tunable length and diameter. ALD (atomic layer deposition) is subsequently used to coat this substrate conformally with a highly pure Sb₂S₃ light absorber layer under an inert atmosphere. The high absorption coefficient of Sb₂S₃ as compared to molecular dyes allows for the utilization of very short nanotubes, which facilitates the infiltration of the organic hole transport material and formation of a p–i–n heterojunction in an interdigitated and tunable geometry. We investigate the influence of nanotube length and of the absorber thickness to enhance the photocurrent value to twice that of planar reference structures.

TiO₂ nanotubes generated by anodization of metallic titanium sputter-coated on indium tin oxide (ITO) substrates are used as a conductive scaffold for all-solid-state Sb₂S₃-sensitized extremely thin absorber (ETA) solar cells.