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Chronic otitis media is often connected to Eustachian tube dysfunction. As successful treatment cannot be guaranteed with the currently available options, the aim is to develop a stent for the Eustachian tube (ET). Over the course of this development, different prototypes were generated and tested in ex vivo experiments. Four different prototypes of an ET stent and one commercially available coronary stent were implanted in the ET of seven human donor bodies. The position of the stents was verified by cone beam CT. The implanted ETs were harvested, embedded in resin and ground at 200 µm steps. Resulting images of the single steps were used to generate 3D models. The 3D models were then evaluated regarding position of the stent in the ET, its diameters, amount of squeezing, orientation of the axes and other parameters. Virtual reconstruction of the implanted ET was successful in all cases and revealed one incorrect stent placement. The cross-section increased for all metal stents in direction from the isthmus towards the pharyngeal orifice of the ET. Depending on the individual design of the metal stents (open or closed design), the shape varied also between different positions along a single stent. In contrast, the cross-section area and shape remained constant along the polymeric prototype. With the current investigation, insight into the behavior of different prototypes of ET stents was gained, which can help in defining the specifications for the intended ET stent.

Objectives: To develop a new dye formulation for vitreoretinal surgery, which shows increased transparency for better intraoperative handling with better parameters important for use., Methods and Analysis: A new blue dye, DDG, was synthesised and tested for toxicity and staining. Diglycerol as new density-increasing additive was identified, and its toxicity and lack of influence of the staining with trypan blue (TB) on a collagen membrane as model for the epiretinal membrane was determined. Transparency of the dye solution was evaluated., Results: DDG is as alternative to Brilliant Blue G (BBG), with good staining properties for interna limitans models, and a good safety profile. Diglycerol is a new non-toxic additive replacing PEG3350, with reduced viscosity and no reduction in staining, allowing the reduction of TB to achieve the same staining level of the collagen membrane by 40%, with greater transparency of the dye solution and reduced viscosity. Both factors should facilitate a safe removal during surgery., Conclusion: A new dye preparation with improved performance in comparison to marketed combinations of BBG and TB was developed. Its reduced TB concentration and viscosity with maintained density allow better tolerance and handling., Competing Interests: Competing interests: AM and DG have a patent on use of diglycerol in vitreoretinal surgery. DG has submitted a patent on DDG in vitreoretinal surgery, and a patent on solutions for staining the posterior with reduced TB concentrations., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The phosphinoindenyl rare-earth metal complexes [1-(Ph 2 P)-η 5 -C 9 H 6 ] 2 Ln III N(SiMe 3 ) 2 , Ln = La (1-La), Sm (1-Sm), were prepared by heating two equivalents of 1-(Ph 2 P)C 9 H 7 with Ln III [N(SiMe 3 ) 2 ] 3 in toluene at 100 °C. The treatment of 1-La with one equivalent of benzonitrile gave (PhCN)[1-(Ph 2 P)-η 5 -C 9 H 6 ] 2 La III N(SiMe 3 ) 2 , 2, while no adduct was formed in case of the samarium derivative 1-Sm. The reaction of 1-La and 1-Sm with two equivalents of benzyl azide yielded the (phosphazido)indenyl complexes {1-[BnN 3 -κ N (Ph 2 )P]-η 5 -C 9 H 6 }{1-[BnN 3 -κ 2 N , N '(Ph 2 )P]C 9 H 6 }Ln III N(SiMe 3 ) 2 , Ln = La (3-La), Sm (3-Sm), respectively. The five complexes catalyse the intramolecular hydroamination/cyclisation of 2,2-diphenylpent-4-ene-1-amine using 2% catalyst loading. All compounds were characterised by NMR and UV-Vis spectroscopy, single-crystal X-ray diffraction, and elemental analysis and DFT calculations were performed for 3-La.

Background/aims: von Willebrand factor (vWf) is an adhesive glycoprotein known to play a role in hemostasis and in tissue injury. It is found in high levels in plasma of patients with acute hepatic failure and chronic liver disease. The aim of this study was to investigate the pattern of tissue vWf in acute liver failure in humans., Methodology: We studied vWf immunostaining and mRNA expression in the liver of three patients with fulminant liver failure, two patients with chronic liver disease, and two controls. PECAM-1 (CD31) immunostaining and mRNA expression were used as an additional endothelial marker., Results: In chronic liver cirrhosis, vWf deposits were strongly detected at the scar-parenchyma interface. In fulminant hepatic failure, intense deposits were seen in tissue sections in the area of necrosis. A similar pattern of immunostaining was seen with PECAM-1. vWf transcripts were abundant in the liver of patients with chronic disease and minimally expressed in patients with acute hepatic failure and in controls., Conclusions: vWf is deposited within the liver sinusoids early after liver damage. The factor is only partially produced locally during the acute phase of the disease, but is overproduced in chronic disease states. These changes may suggest a role for vWf in liver injury and repair.

Background/aims: Von Willebrand factor (vWf) is found in high levels in plasma of patients with acute and chronic liver disease. The role of vWf in liver injury and repair is unknown. We studied the effect of liver mass and remodeling on plasma and tissue vWf after partial hepatectomy., Methods: Rats were sacrificed postoperatively at intervals ranging from 60 min to 5 days, and vWf plasma levels were measured by enzyme-linked immunosorbent assay, using rabbit anti-human vWf, and by immunoperoxidase on cryosections, using rabbit anti-vWf/factor VIII. Northern blot hybridization was prepared with a complementary DNA specific to human vWf., Results: vWf plasma levels increased early after sham operation and after 70% partial hepatectomy. The highest levels were reached at 24 h, remaining high for 5 days. Immunostaining showed intense staining of sinusoidal lining cells 4 h after partial hepatectomy, remaining so for 5 days. Non-significant changes in overall liver messenger RNA expression of vWf were seen over 5 days in sham operation and partial hepatectomy., Conclusions: After partial hepatectomy, plasma vWf is increased, probably due to both acute-phase reaction and decreased degradation. An increase in sinusoidal vWf immunostaining may suggest a role for this factor in tissue remodeling.

Background/aims: Platelet-endothelial cell adhesion molecule (PECAM)-1 is suggested to be critical for transmigration processes. It is a matter of debate whether PECAM-1 is expressed in liver sinusoids and whether it is involved in liver inflammation., Methods: Indirect immunostaining and in situ hybridization was used to analyze PECAM-1 gene expression in normal and diseased rat and human livers as well as in isolated rat sinusoidal endothelial cells (SECs), hepatic stellate cells and hepatocytes. At various time points after the administration of CCl4 (6 h, 24 h, 48 h, and 72 h), PECAM-1 gene expression was analyzed in livers and in SECs by immunostaining, and Northern blot analysis., Results: In normal rat or human livers PECAM-1 immunoreactivity was detected along the sinusoids in a pattern similar to ICAM-1 staining. PECAM-1 specific transcripts were detected in freshly isolated and cultured SECs. After a single CCl4-administration, PECAM-1 immunoreactivity did not increase along the sinusoids in contrast to the early increase of ICAM-1. Northern blot analysis indicated that PECAM-1 expression in liver tissue and in isolated SECs does not increase after a single administration of CCl4, whereas ICAM-1 steady-state level increased after 6 h. In diseased human livers PECAM-1 was detectable along the sinusoids, within inflammatory infiltrates and within fibrotic septa. Neither in acutely nor chronically diseased human livers was an obvious increase of PECAM-1 immunoreactivity detectable., Conclusions: PECAM-1 is expressed by SECs. In contrast to ICAM-1, PECAM-1 transcript level is not enhanced during liver damage.

The mechanisms leading to the infiltration of inflammatory cells into the liver and to liver cell necrosis remain undefined. To elucidate this process, the present work analyzes the kinetics of the expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation of inflammatory leukocyte function antigen-1 (LFA-1)-positive cells in relation to the appearance of hepatocellular necrosis in the model of acute carbontetrachloride (CCl4)-induced liver injury. ICAM-1- and LFA-1-immunoreactivity was analyzed in normal livers and in livers obtained 3, 6, 9, 12, 18, 24, 48, and 72 hours after CCl4-administration, as well as in liver cells isolated 3, 6, 9, 12, 18, and 24 hours after CCl4-administration. Total RNA extracted from livers and cells was used for Northern blot analysis. ICAM-1-positivity, which was detected along the sinusoids in normal rat livers, increased 3 to 6 hours after CCl4-administration and finally accumulated in the necrotic areas (24 to 48 hours post-administration). ICAM-1 steady-state mRNA levels in liver tissue increased 3 to 6 hours after CCl4-treatment and returned to normal levels at 48 hours after treatment. Increased amounts of ICAM-1-specific transcripts could be observed in isolated sinusoidal endothelial cells and in hepatocytes as early as 3 to 6 hours after CCl4-administration. In normal rat livers, a few LFA-1-immunoreactive cells were present around the vessel walls. Starting 12 hours after CCl4-administration, the number of LFA-1-immunoreactive cells increased around the vessel walls and along the sinusoids, accumulating later in the necrotic areas. In accordance, the number of mononuclear phagocytes isolated from the liver increased 12 hours after CCl4-treatment. These data demonstrate an early up-regulation of ICAM-1 in liver cells and the accumulation of LFA-1-expressing cells prior to the development of necrotic areas. The up-regulation of ICAM-1 and accumulation of inflammatory cells seem to be critical for the induction of CCl4-induced hepatotoxicity.