SDF‐1/CXCR4/CXCR7 is pivotal for vascular smooth muscle cell proliferation and chronic allograft vasculopathy

Chronic rejection remains a major obstacle in transplant medicine. Recent studies suggest a crucial role of the chemokine SDF‐1 on neointima formation after injury. Here, we investigate the potential therapeutic effect of inhibiting the SDF‐1/CXCR4/CXCR7 axis with an anti‐SDF‐1 Spiegelmer (NOX‐A12) on the development of chronic allograft vasculopathy. Heterotopic heart transplants from H‐2bm12 to B6 mice and aortic transplants from Balb/c to B6 were performed. Mice were treated with NOX‐A12. Control animals received a nonfunctional Spiegelmer (revNOX‐A12). Samples were retrieved at different time points and analysed by histology, RT‐PCR and proliferation assay. Blockade of SDF‐1 caused a significant decrease in neointima formation as measured by intima/media ratio (1.0 ± 0.1 vs. 1.8 ± 0.1, P < 0.001 AoTx; 0.35 ± 0.05 vs. 1.13 ± 0.27, P < 0.05 HTx). In vitro treatment of primary vascular smooth muscle cells with NOX‐A12 showed a significant reduction in proliferation (0.42 ± 0.04 vs. 0.24 ± 0.03, P < 0.05). TGF‐β, TNF‐α and IL‐6 levels were significantly reduced under SDF‐1 inhibition (3.42 ± 0.37 vs. 1.67 ± 0.33, P < 0.05; 2.18 ± 0.37 vs. 1.0 ± 0.39, P < 0.05; 2.18 ± 0.26 vs. 1.6 ± 0.1, P < 0.05). SDF‐1/CXCR4/CXCR7 plays a critical role in the development of chronic allograft vasculopathy (CAV). Therefore, pharmacological inhibition of SDF‐1 with NOX‐A12 may represent a therapeutic option to ameliorate chronic rejection changes.     

Obtaining lignocellulosic biomass-based catalysts and their catalytic activity in cellobiose hydrolysis and acetic acid esterification reactions

Global challenges prompt the world to modify its strategies and shift from a fossil-fuel-based economy to a bio-resource-based one with the production of renewable biomass chemicals. Different processes exist that allow the transformation of raw biomass into desirable bio-based products and/or energy. In this work different biochars that were obtained as a by-product from birch chip fast pyrolysis and carbonization were used as is or chemically/physically treated. These sulfonated carbon catalysts were compared to a commercially available sulfonated styrene-divinylbenzene macroreticular resin (Dowex 50W X8). Characterisation (water content and pH value, FTIR, base titration, element analysis and N₂ desorption) was done to evaluate the obtained sulfonated biocarbon catalysts. Catalytic activity was tested using cellobiose (CB) hydrolysis and acetic acid esterification. For the catalytic CB hydrolysis, we tested the reaction temperature, time and CB and catalyst mass ratios. The determined optimal conditions were 120 °C and 24 h, with CB and catalyst mass ratio 1 : 5. The highest glucose yield was observed for biochar obtained from the birch chip fast pyrolysis process (BC_Py-H₂SO₄) – 92% within 24 h for 120 °C. Comparably high glucose yield was observed for biochar that was obtained in birch chip carbonization (BC_Carbon-H₂SO₄) – 86% within 24 h for 120 °C.

In this work different biochars that were obtained as a by-product from birch chip fast pyrolysis and carbonization were used as is or chemically/physically treated. The characterisation was done using CB hydrolysis and acetic acid esterification.     

Modeling the Nonlinear Deformation of Highly Porous Cellular Plastics Filled with Clay Nanoplatelets

Rigid low-density plastic foams subjected to mechanical loads typically exhibit a nonlinear deformation stage preceding failure. At moderate strains, when the geometrical nonlinearity is negligible, such foam response is predominantly caused by the nonlinearity of deformation of their principal structural elements—foam struts. Orientational averaging of stresses in foam struts enables estimation of the stresses taken up by foams at a given applied strain. Based on a structural model of highly porous anisotropic cellular plastics filled with clay nanoplatelets and the orientational averaging, a method for calculating their nonlinear deformation is derived in terms of structural parameters of the porous material, the mechanical properties of the monolithic polymer, and filler particles and their spatial orientation. The method is applied to predicting the tensile stress-strain diagrams of organoclay-filled low-density rigid polyurethane foams, and reasonable agreement with experimental data is demonstrated.     

Coventry Award paper. Backsurface wear and deformation in polyethylene tibial inserts retrieved postmortem

Wear and deformation were characterized at the backsurface of 25 posterior cruciate-retaining total knee arthroplasty polyethylene inserts retrieved postmortem from 20 subjects. The mean implantation time was 64.1 months (range, 4-156 months). The backsurface of the inserts was inspected using a stereomicroscope with a digital optical system. Coronal histologic sections of 13 proximal tibias were inspected for the presence and extent of penetration of granuloma. Damage to the backsurface was limited. Polishing was recorded on 21 (84%) of the inserts and abrasive wear on five (20%) inserts. Pitting was present in 21 (84%) components, but involved less than 1% of the area in all but one of these components. Delamination and cracking were not observed. Extrusions were seen in all 10 of the components that had screw holes in the tibial tray. A correlation was found between the depth of penetration of the granuloma along the posteromedial screw and the height of the corresponding extrusion. The anteroposterior profiles showed a concave deformation of the backsurface in 24 (96 %) of the cases. The concave deformation of tibial inserts may facilitate accumulation and transportation of wear debris to the tibial bone-implant interface through the screw holes in implants designed for cementless fixation.     

Stem curvature and load angle influence the initial relative bone-implant motion of cementless femoral stems

A 6 df measurement system was used to investigate the initial relative bone-implant motion of two types of cementless total hip replacement femoral components—a straight stem and a curved stem. Five pairs of fresh frozen femurs from human cadavers were tested with loads applied to the femoral head at angles characteristic of level walking, stair-climbing, and rising from a chair. The most important findings were that (a) the resultant proximal translations were twice as high with the straight stem as with the curved stem at load angles encountered in stair-climbing and rising from a chair, (b) both stem types had more motion at load angles encountered in stair-climbing and rising from a chair than in level walking, with the increases ranging from 3 to 14-fold, (c) there was as much as 66-fold more motion distally than proximally, and (d) the amount of interface motion varied by 5-fold between the medial and lateral surfaces of the distal part of the implant because of the combined effects of translation and rotation. The amount of initial bone-implant motion of the femoral component was found to be particularly sensitive to off-axis loading; this suggests that stair-climbing and rising from a chair should be avoided in the early postoperative period when a cementless porous-coated femoral stem has been used.     

Occupational risks for uveal melanoma results from a case-control study in nine European countries

Objective Uveal melanoma is a rare disease with poor prognosis and largely unknown etiology. We studied potential occupational risk factors.Methods A population based case-control study was undertaken during 1995–1997 in nine European countries using population and colon cancer controls with personal interviews. Occupational exposure to sunlight and artificial UV radiation was assessed with a job exposure matrix. In total, 320 uveal melanoma cases were eligible at pathology review, and 292 cases were interviewed, participation 91%. Out of 3357 population controls, 2062 were interviewed, 61%, and out of 1272 cancer controls 1094 were interviewed, 86%.Results Using population controls, occupational exposure to sunlight was not associated with an increased risk (RR=1.24, 95% CI=0.88−1.74), while an excess risk found with use of colon cancer controls was attributed to confounding factors. An excess risk in welders was restricted to the French part of the data. Cooks, RR=2.40; cleaners, RR 2.15; and laundry workers, RR=3.14, were at increased risk of uveal melanoma.Conclusion Our study does overall not support an association between occupational sunlight exposure and risk of uveal melanoma. The finding of an excess risk of eye melanoma in cooks in several European countries is intriguing.     

Breast cancer mortality patterns and time trends in 10 new EU member states: mortality declining in young women, but still increasing in the elderly

Breast cancer is the cancer diagnosed most frequently in women worldwide. In Europe it is the most common cancer in the female population, with approximately 350,000 new cases diagnosed each year including 130,000 deaths. Incidence rates are increasing in the majority of European countries, whereas a decline in mortality rates has been observed in many West European countries since the late 1980s and early 1990s. Our study examines breast cancer mortality patterns and time trends in the new European Union (EU) member states and compares them with the situation in current EU member states. A Joinpoint regression analysis was used to assess temporal changes in mortality rates and the trends examined in the light of known risk factors, screening programs and advances in treatment. In the majority of the countries analyzed, a deceleration in the increase of mortality rates appeared, followed by a decrease of mortality in many of them in the second half of the 1990s. The declining tendency was visible primarily in young women, and to a lesser extent in middle-aged women, whereas in elderly women a continuing increase of mortality was observed. Analysis of mortality data, information from previous publications, as well as analysis of known factors influencing breast cancer risk suggest that changes observed are due mainly to recent advances in treatment rather than changes in lifestyle risk factors or the result of screening programs. Early detection and a shift toward more favorable stage distribution could have played the leading role for mortality decline in younger patients.     

Effects of 5-acetyl(carbamoyl)-6-methylsulfanyl-1,4-dihydropyridine-5-carbonitriles on rat liver mitochondrial function

It is increasingly recognised that mitochondria are potential targets to pharmacological and toxicological actions of membrane-active agents, including some 1,4-dihydropyridines derivatives (DHPs). The 5-acetyl(carbamoyl)-6-methylsulfanyl-1,4-dihydropyridine-5-carbonitriles (OSI-1146, OSI-3701, OSI-3761, and OSI-9642) is a new group of DHPs with minor differences on the molecular structure. It has also been shown that OSI-1146 displays cardiovascular, antioxidant, and antiradical activities, whereas OSI-3701 and OSI-3761 display hepatoprotective activity. Due to their protective properties, this group of DHPs may be potentially useful for the treatment of several pathological processes, including those associated with oxidative stress. However, the cellular targets for their pharmacological actions have not been investigated. The presented study, using isolated rat liver mitochondria was designed to investigate if mitochondria are a cellular target for the pharmacological and/or toxicological actions of these new group of DHPs. We studied the direct influence of these DHPs on rat liver mitochondrial function [bioenergetics, membrane permeability transition (MPT), and oxidative stress]. It was shown that OSI-1146, OSI-3761, and OSI-9642, in the concentration range of up to 200 μM, interfered with mitochondrial bioenergetics by affecting complexes I and II of the mitochondrial respiratory chain, the ATPase activity, and mitochondrial inner membrane permeability to protons. However, the effects of OSI-1146 were higher than those of OSI-3761 and OSI-9642. The remaining compound, OSI-3701, had no effect on the bioenergetic parameters tested. All the compounds increased the susceptibility of mitochondria to MPT, but, OSI-3701, not affecting the bioenergetic parameters, was the most potent. Moreover, all the compounds protected mitochondria against lipid peroxidation induced by the oxidant pair ADP/Fe²⁺, but OSI-1146 was also the most potent. In conclusion, our results indicate that mitochondria are the potential intracellular targets for both protective and toxicological actions of the DHP compounds studied, suggesting that the potential use of these compounds as therapeutic agents should carefully consider their toxic effects to mitochondria.