Acid-sensing ion channel 2 (asic 2) and trkb interrelationships within the intervertebral disc

The cells of the intervertebral disc (IVD) have an unusual acidic and hyperosmotic microenvironment. They express acid-sensing ion channels (ASICs), gated by extracellular protons and mechanical forces, as well as neurotrophins and their signalling receptors. In the nervous tissues some neurotrophins regulate the expression of ASICs. The expression of ASIC2 and TrkB in human normal and degenerated IVD was assessed using quantitative-PCR, Western blot, and immunohistochemistry. Moreover, we investigated immunohistochemically the expression of ASIC2 in the IVD of TrkB-deficient mice. ASIC2 and TrkB mRNAs were found in normal human IVD and both increased significantly in degenerated IVD. ASIC2 and TrkB proteins were also found co-localized in a variable percentage of cells, being significantly higher in degenerated IVD than in controls. The murine IVD displayed ASIC2 immunoreactivity which was absent in the IVD of TrkB-deficient mice. Present results demonstrate the occurrence of ASIC2 and TrkB in the human IVD, and the increased expression of both in pathological IVD suggest their involvement in IVD degeneration. These data also suggest that TrkB-ligands might be involved in the regulation of ASIC2 expression, and therefore in mechanisms by which the IVD cells accommodate to low pH and hypertonicity.     

Finite element analysis of the influence of the offset placement of an implant-supported prosthesis on bone stress distribution

The aim of this study was to evaluate the influence of the straight alignment versus distal offset placement of an implant-supported prosthesis (using implants with different diameters: 4 mm, 4.5 mm, and 5 mm) on bone stress distribution. 3D finite element models of a straight configuration and different offset configurations of the implant-supported prosthesis (until 2.4 mm distal offset) were evaluated for the three implant diameters. A mesial load of 200 N and a distal load of 230 N were applied to the prosthesis. Results showed that implant offset provokes an opposite effect in bone stress depending on the exposed mesial or distal force. The former increases stress whereas the latter induces a dissipation of bone stress proportional to the offset. From these two forces, an optimal offset is created in which maximum bone stress is reduced in the range of 7-8% compared with the straight configuration. Increasing implant diameter from 4 to 5 mm decreased bone stress in 30% for all configurations. These data suggests that offset implant placement apart from enabling an optimal aesthetic restoration, reduces bone stress compared with the straight configuration. The use of wider implants permitted the reduction of the maximum bone stress in all the simulated configurations.     

Autologous fibrin matrices: a potential source of biological mediators that modulate tendon cell activities

The use of autologous fibrin matrices has been proposed as a therapeutic strategy for the local and physiological delivery of growth factors in the treatment of several clinical conditions requiring tendon healing or tendon graft remodelling. In the present work, we investigated the proliferation, synthesis of type-I collagen and angiogenic factors by tendon cells seeded on platelet-rich (PR) and platelet-poor (PP) matrices. Furthermore, in vivo cellular and vascular effects of each treatment were examined after infiltration in Achilles tendon in sheep. Results showed that the presence of platelets within the fibrin matrices increased significantly the proliferation of tendon cells. Additionally, cultured tendon cells synthesised type I collagen and angiogenic factors such as VEGF and HGF. The synthesis of VEGF, but not of HGF, was significantly higher when platelets were present within the matrix. In the sheep model, the injection of pre-clotted plasma within tendons increased cellular density and promoted neovascularization. These results indicate that administration of fibrin matrices is a safe and easy strategy that may open new avenues for enhancing tissue healing and remodelling and influences the process of regeneration in clinical situations characterised by a poor healing outcome.     

Recent advances in the use of encapsulated cells for effective delivery of therapeutics

Cell encapsulation can be defined as a living cell approach for the long-term delivery of therapeutic products. It consists of the immobilization of therapeutically active cells within a general polymer matrix that permits the ingress of nutrients and oxygen and the egress of therapeutic protein products but impedes the immune contact of the enclosed cells. In recent decades many attempts have evaluated the potential of this technology to release therapeutic agents for the treatment of different pathologies and disorders. At present, cell encapsulation may be used as a technological platform to improve knowledge and clinical use of stem cells. This review describes the main issues related to this cell-based approach and summarizes some of the most interesting therapeutic applications.     

A novel CYBA variant, the -675A/T polymorphism, is associated with essential hypertension

OBJECTIVE: Oxidative stress is implicated in hypertension and the NADPH oxidase systems constitute the main source of superoxide in vascular wall. We searched for new polymorphisms within the CYBA promoter, the human gene that encodes the p22phox protein, and studied their potential association with essential hypertension. DESIGN: A case-control study in a random sample of the general population. METHODS: CYBA polymorphisms were determined by restriction fragment length polymorphism and allelic discrimination. NADPH oxidase activity was quantified in phagocytic cells by chemiluminescence. RESULTS: We identified three novel polymorphisms, at positions -852, -675 and -536 from the ATG codon. Only the -675(A/T) polymorphism associated with essential hypertension. The prevalence of the TT genotype and the T allele frequency were significantly higher (P < 0.05) in hypertensives than in normotensives. Furthermore, TT hypertensives exhibited higher (P < 0.05) systolic blood pressure values than TA/AA hypertensives. Increased phagocytic NADPH oxidase activity was observed in TT subjects compared to TA and AA individuals (P < 0.05). Enhanced carotid intima-media thickness, a surrogate marker of atherosclerosis, was found in TT subjects compared to TA and AA individuals (P < 0.05). Finally, mutagenesis experiments demonstrated a functional role of this polymorphism on the CYBA promoter activity. CONCLUSION: The -675 (A/T) CYBA polymorphism may be a novel genetic marker associated with essential hypertension. Furthermore, TT subjects exhibit features of NADPH oxidase-mediated oxidative stress and asymptomatic atherosclerosis.