Effect of Ionizing Radiation on Artificial (Planar) Lipid Membranes. II. The Ion Carriers Valinomycin and Nonactin as Probes for Radiation Induced Structural Changes of the Membrane

Summary

Planar lipid membranes in the presence of the ion carriers valinomycin or nonactin were irradiated with 14 MeV electrons from a linear accelerator. A large increase of the membrane conductance by up to more than two orders of magnitude was found. The effect is virtually abolished either at high pH, or in the absence of oxygen, or in the presence of the radical scavenger ethanol. A further prerequisite for the effect is the presence of unsaturated fatty acid residues. A kinetic analysis of the carrier transport model based on current-voltage curves and on voltage-jump relaxation experiments was performed as a function of radiation dose. Only the translocation rate constant, k_MS, of the charged carrier-ion complex was found to be influenced by irradiation. The effect is interpreted as an increase of the polarity (dielectric constant) of the membrane interior induced by the presence of polar products of lipid peroxidation. A combined action of OH- and HO₂-radicals seems to be responsible for the phenomena. At large radiation doses (? 10³ Gy) a reduction of the membrane conductance was observed. This is interpreted as an increased microviscosity, possibly caused by cross-linking of fatty acid residues. Ion carriers represent sensitive probes of radiation induced membrane damage.     

Automated tube voltage adaptation in head and neck computed tomography between 120 and 100 kV: effects on image quality and radiation dose

Introduction

Low tube voltage allows for computed tomography (CT) imaging with increased iodine contrast at reduced radiation dose. We sought to evaluate the image quality and potential dose reduction using a combination of attenuation based tube current modulation (TCM) and automated tube voltage adaptation (TVA) between 100 and 120 kV in CT of the head and neck.

Methods

One hundred thirty consecutive patients with indication for head and neck CT were examined with a 128-slice system capable of TCM and TVA. Reference protocol was set at 120 kV. Tube voltage was reduced to 100 kV whenever proposed by automated analysis of the localizer. An additional small scan aligned to the jaw was performed at a fixed 120 kV setting. Image quality was assessed by two radiologists on a standardized Likert-scale and measurements of signal- (SNR) and contrast-to-noise ratio (CNR). Radiation dose was assessed as CTDI_vol.

Results

Diagnostic image quality was excellent in both groups and did not differ significantly (p?=?0.34). Image noise in the 100 kV data was increased and SNR decreased (17.8/9.6) in the jugular veins and the sternocleidomastoid muscle when compared to 120 kV (SNR 24.4/10.3), but not in fatty tissue and air. However, CNR did not differ statistically significant between 100 (23.5/14.4/9.4) and 120 kV data (24.2/15.3/8.6) while radiation dose was decreased by 7–8 %.

Conclusions

TVA between 100 and 120 kV in combination with TCM led to a radiation dose reduction compared to TCM alone, while keeping CNR constant though maintaining diagnostic image quality.     

Wedge volume and osteotomy surface depend on surgical technique for high tibial osteotomy

Purpose

Biplanar open-wedge high tibial osteotomy (HTO) is thought to promote rapid bone healing due to the increased cancellous bone surface compared to other HTO techniques. However, precise data on the bone surface area and wedge volume resulting from both open- and closed-wedge HTO techniques remain unknown. We hypothesized that biplanar rather than uniplanar HTO better reflects the ideal geometrical requirements for bone healing, representing a large cancellous bone surface combined with a small wedge volume.

Methods

Tibial saw bones were assigned to 4 different groups of valgisation high tibial osteotomies: group 1: open-wedge uniplanar HTO; group 2: open-wedge biplanar HTO with ascending frontal cut; group 3: open-wedge biplanar HTO with descending frontal cut (retrotubercule osteotomy technique), and group 4: closed-wedge uniplanar HTO. Bone surface areas of all osteotomy planes were quantified. Wedge volumes were determined using a prism-based algorithm, applying standardized wedge heights of 5, 10, and 15 mm.

Results

The open-wedge biplanar osteotomy with a descending frontal cut (group 3) created significantly larger bone surfaces compared to the “classic” biplanar technique with an ascending frontal cut (group 2) and compared to all uniplanar techniques. Bone surfaces after the classic open-wedge technique (group 2) were slightly larger compared to all uniplanar techniques (group 1 and 4). No significant differences of wedge volumes were found between the retrotubercle (group 3) and classic open-wedge techniques (group 2). Wedge volumes were significantly higher in the uniplanar open-wedge technique (group 1) compared to the biplanar open-wedge techniques (group 2 and 3).

Conclusion

Bone geometry following HTO suggests that the biplanar open-wedge techniques simultaneously create smaller wedge volumes and larger bone surface areas compared to the uniplanar open-wedge techniques. The relatively neglected closed-wedge technique still offers in theory the best healing potential, characterized by an almost absent wedge volume and a large bone-to-bone contact area. Although this idealized geometric view on bony geometry excludes all biologic factors that influence bone healing, the current data suggest a general rule for the applied standard osteotomy techniques and all of their surgical modifications: reducing the amount of slow gap healing and simultaneously increasing the area of faster contact healing may be beneficial for osteotomy healing. Thus, a biplanar rather than a uniplanar osteotomy may be performed for high tibial osteotomy in clinical practice.     

Culture of human bone marrow-derived mesenchymal stem cells on of poly(l-lactic acid) scaffolds: potential application for the tissue engineering of cartilage

Purpose

Due to the attractive properties of poly(l-lactic acid) (PLLA) for tissue engineering, the aim was to determine the growth and differentiation capacity of mesenchymal stromal cells (MSCs) in PLLA scaffolds and their potential use in the treatment of cartilage diseases.

Methods

MSCs were cultured in PLLA films and thin porous membranes to study adherence and proliferation. Permeability and porosity were determined for the different scaffolds employed. The optimal conditions for cell seeding were first determined, as well as cell density and distribution inside the PLLA. Scaffolds were then maintained in expansion or chondrogenic differentiation media for 21 days. Apoptosis, proliferation and chondrogenic differentiation was assessed after 21 days in culture by immunohistochemistry. Mechanical characteristics of scaffolds were determined before and after cell seeding.

Results

MSCs uniformly adhered to PLLA films as well as to porous membranes. Proliferation was detected only in monolayers of pure PLLA, but was no longer detected after 10 days. Mechanical characterization of PLLA scaffolds showed differences in the apparent compression elastic modulus for the two sizes used. After determining high efficiencies of seeding, the production of extracellular matrix (ECM) was determined and contained aggrecan and collagens type I and X. ECM produced by the cells induced a twofold increase in the apparent elastic modulus of the composite.

Conclusions

Biocompatible PLLA scaffolds have been developed that can be efficiently loaded with MSCs. The scaffold supports chondrogenic differentiation and ECM deposition that improves the mechanics of the scaffold. Although this improvement does not met the expectations of a hyaline-like cartilage ECM, in part due to the lack of a mechanical stimulation, their potential use in the treatment of cartilage pathologies encourages to improve the mechanical component.     

Comparison of different methods of spatial normalization of FDG-PET brain images in the voxel-wise analysis of MCI patients and controls

Objective

One of the most interesting clinical applications of 18F-FDG PET imaging in neurodegenerative pathologies is that of establishing the prognosis of patients with mild cognitive impairment (MCI), some of whom have a high risk of progressing to Alzheimer’s disease (AD). One method of analyzing these images is to perform statistical parametric mapping (SPM) analysis. Spatial normalization is a critical step in such an analysis. The purpose of this study was to assess the effect of using different methods of spatial normalization on the results of SPM analysis of 18F-FDG PET images by comparing patients with MCI and controls.

Methods

We evaluated the results of three spatial normalization methods in an SPM analysis by comparing patients diagnosed with MCI with a group of control subjects. We tested three methods of spatial normalization: MRI-DARTEL and MRI-SPM8, which combine structural and functional images, and FDG-SPM8, which is based on the functional images only.

Results

The results obtained with the three methods were consistent in terms of the main pattern of functional alterations detected; namely, a bilateral reduction in glucose metabolism in the frontal and parietal cortices in the patient group. However, MRI-SPM8 also revealed differences in the left temporal cortex, and MRI-DARTEL revealed further differences in the left temporal cortex, precuneus, and left posterior cingulate.

Conclusions

The results obtained with MRI-DARTEL were the most consistent with the pattern of changes in AD. When we compared our observations with those of previous reports, MRI-SPM8 and FDG-SPM8 seemed to show an incomplete pattern. Our results suggest that basing the spatial normalization method on functional images only can considerably impair the results of SPM analysis of 18F-FDG PET studies.     

The plasminogen activating system in the pathogenesis of Alzheimer’s disease

Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor functions.Alzheimer’s disease(AD)accounts for approximately 60–80%of all cases of dementia,and neuropathologically is characterized by extracellular deposits of insoluble amyloid-β(Aβ)and intracellular aggregates of hyperphosphorylated tau.Significantly,although for a long time it was believed that the extracellular accumulation of Aβwas the culprit of the symptoms observed in these patients,more recent studies have shown that cognitive decline in people suffering this disease is associated with soluble Aβ-induced synaptic dysfunction instead of the formation of insoluble Aβ-containing extracellular plaques.These observations are translationally relevant because soluble Aβ-induced synaptic dysfunction is an early event in AD that precedes neuronal death,and thus is amenable to therapeutic interventions to prevent cognitive decline before the progression to irreversible brain damage.The plasminogen activating(PA)system is an enzymatic cascade that triggers the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases:tissue-type plasminogen activator(tPA)and urokinase-type plasminogen activator(uPA).Experimental evidence reported over the last three decades has shown that tPA and uPA play a role in the pathogenesis of AD.However,these studies have focused on the ability of these plasminogen activators to trigger plasmin-induced cleavage of insoluble Aβ-containing extracellular plaques.In contrast,recent evidence indicates that activity-dependent release of uPA from the presynaptic terminal of cerebral cortical neurons protects the synapse from the deleterious effects of soluble Aβvia a mechanism that does not require plasmin generation or the cleavage of Aβfibrils.Below we discuss the role of the PA system in the pathogenesis of AD and the translational relevance of data published to this date.     

Exercise-based cardiac rehabilitation and parasympathetic function in patients with coronary artery disease: a systematic review and meta-analysis

Clinical Autonomic Research - The effects of exercise-based cardiac rehabilitation (CR) on parasympathetic modulation are controversial. This systematic review and meta-analysis aims to (a)...     

Galectin-1 Expression in CD8+ T Lymphocytes Controls Inflammation in Contact Hypersensitivity

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Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab

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