Search

The blood–brain barrier (BBB) constitutes a distinctive and tightly regulated interface between the brain and the peripheral circulation. The objective of studies was to compare responses of human endothelial cells representing the model of blood vessels – EA.hy926 and HUVEC cells and the model of the brain endothelial barrier – HBEC5i cells to silver nanoparticles (SNPs). A contact of SNPs with endothelial cells resulted in a formation of SNP agglomerates. Consequently, the SNPs uptake by endothelial cells affected cell viability and membrane integrity however observed responses were different. Brain endothelial barrier HBEC5i cells were much less vulnerable to SNPs toxicity comparing to EA.hy926 and HUVEC cells. It can be ascribed to the presence of specialized cellular components of the brain barrier, protecting HBEC5i cells against toxic SNPs. Fundamental understanding of SNPs inducing the BBB dysfunction may initiate engineering novel SNPs which are safe for the BBB and thereby safe for the brain. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The authors have been using patient-specific implants since 2006 and are constantly looking for new reconstructive materials, in order to create precise implants for orbital reconstruction. Such materials should be biocompatible and stable in the human body, as well as easy to machine and form into complex 3D shapes. Biocompatible ultrahigh molecular weight polyethylene (UHMW-PE) has several unique properties including high impact strength and a low friction coefficient that result in self-lubricating and thus non-sticking surfaces after processing. Aim: To present the concept of a patient-specific, UHMW-PE orbital wall implant. Materials and methods: The material used to manufacture the orbital implant was UHMW-PE converted into a solid block of medical polymer from a powder material. A delayed treatment unilateral orbital fracture case was chosen for reconstruction with patient-specific orbital wall implant. On the basis of computerized tomography, a virtual model of both orbits was prepared. The injured orbit was significantly enlarged due to dislocation of its walls. The 3D model of the facial skeleton was symmetrically divided into two parts. This resulted in two models – left and right orbit, then the uninjured orbit was superimposed onto the contralateral side. As a result two surfaces were created; the outer surface (taken from the injured orbit) was used to design the outer surface of the implant, and the inner (taken from the uninjured orbit) for the inner surface. By combining both these surfaces it was possible to determine the unique shape and thickness of the UHMW-PE implant that would allow for accurate reconstruction of the orbit. Following this, the CAD model was transferred to CAM software and a numerical code for a 5-axis milling machine was generated. The manufactured implant was sterilized in gas plasma and used to reconstruct three orbital walls. Results: The thickness of the manufactured implant ranged from 0.2 mm to 1.5 mm and was successfully inserted via transconjunctival approach. The lower, medial and lateral walls were reconstructed. The correct position of the right eyeball was re-established by moving it upward and medially, which resulted in enophthalmos and diplopia correction. The described method features several advantages: accurate reconstruction of the original shape of the orbit, precise modification of local implant thickness during design of the CAD model, structural globe support combined with a thin implant, the possibility of repairing large orbital floor defects, corrections using scissor/scalpel during surgery are relatively uncomplicated, low level of morbidity, smooth edges and gradual, controlled variations in implant thickness between different regions. Disadvantages: changes to the curvature of the implant cannot be made during surgery, implant may require fixing with screws to be stabilized during the early phase of healing, long time required to design and manufacture implants (pre-op) and also UHMW-PE implants are radiolucent and cannot be imaged using X-rays. Conclusion: UHMW-PE appears to have numerous advantages as a material for precise reconstruction of the orbits. Such patient-specific implants are durable, can even be used to reconstruct very thin walls, do not exhibit the high degree of morbidity typical for autogenous bone grafts and result in restoration of vision function. [Copyright &y& Elsevier]

The synthesis and biological evaluation of new diadenosine polyphosphate analogues on blood platelet aggregation are reported. The most active are compounds with a sulfur atom replacing one or both non-bridging oxygens at phosphorus bound to adenosyl residues and hydroxymethyl groups of bis(hydroxymethyl)phosphinic acid. [Copyright &y& Elsevier]

Abstract: Endogenous μ-opioid receptor (MOR) selective peptides, endomorphin-1 (EM-1) and endomorphin-2 (EM-2), unlike so called ‘typical opioids’, are characterized by the presence of Pro2 residue, which is a spacer connecting aromatic pharmacophoric residues. In order to investigate structural requirements for position 2, we synthesized endomorphin analogs incorporating, instead of Pro, unnatural amino acids with six-membered heterocyclic rings, such as piperidine 2-, 3- or 4-carboxylic acids (Pip, Nip and Inp, respectively). (R)-Nip residue turned out to be favourable for improving MOR affinity. Introduction of 2′,6′-dimethyltyrosine (Dmt) instead of Tyr1 led to obtaining [Dmt1, (R)-Nip2]EM-2 which showed exceptional MOR affinity and high stability against enzymatic degradation in rat brain homogenate. In in vivo hot-plate test in mice, this analog given intracerebroventicularly (i.c.v.), produced profound supraspinal analgesia, being much more potent than EM-2. The antinociceptive effect of this analog lasted about 170min and was almost completely reversed by β-funaltrexamine (β-FNA), a selective MOR antagonist. [Copyright &y& Elsevier]