Structural Features of Patients with Drusen-like Deposits and Systemic Lupus Erythematosus

Background: The relevance of drusen-like deposits (DLD) in patients with systemic lupus erythematosus (SLE) is to a large extent uncertain. Their genesis is proposed to be correlated to immune-complex and complement depositions in the framework of SLE. The intention of this study was to determine potential morphological differences in the choroid and retina as well as potential microvascular changes comparing two cohorts of SLE patients divergent in the presence or absence of DLD using multimodal imaging. Methods: Both eyes of 16 SLE patients with DLD were compared to an age- and sex-matched control-group consisting of 16 SLE patients without detectable DLD. Both cohorts were treated with hydroxychloroquine (HCQ) and did not differ in the treatment duration or dosage. Using spectral-domain optical coherence tomography (SD-OCT) choroidal volume measures, choroidal vascularity indices (CVI) and retinal layer segmentation was performed and compared. In addition, by the exploitation of optical coherence tomography angiography vascular density, perfusion density of superficial and deep retinal capillary plexuses and the choriocapillaris were analyzed. For the choroidal OCT-scans, a subset of 51 healthy individuals served as a reference-group. Results: CVI measures revealed a significant reduction in eyes with DLD compared to healthy controls (0.56 (0.54–0.59) versus 0.58 (0.57–0.59) (p = 0.018) and 0.56 (0.54–0.58) versus 0.58 (0.57–0.60) (p < 0.001)). The photoreceptor cell layer presented significant thinning in both eyes of subjects with DLD compared to control subjects without DLD (68.8 ± 7.7 µm vs. 77.1 ± 7.3 µm for right eyes, p = 0.008, and 66.5 ± 10.5 µm vs. 76.1 ± 6.3 µm for left eyes, p = 0.011). OCTA scans revealed no significant changes, yet there could be observed numerically lower values in the capillary plexuses of the retina in eyes with DLD than in eyes without DLD. Conclusions: Our results illustrated significant alterations in the choroidal and retinal analyzes, suggesting a correlation between DLD and the progression of inflammatory processes in the course of SLE leading to retinal degeneration. For this reason, DLD could serve as a biomarker for a more active state of disease

Acute and chronic lung inflammation drives changes in epithelial glycans

IntroductionAsthma is the most common chronic inflammatory disease and it is characterized by leukocyte infiltration and tissue remodeling, with the latter generally referring to collagen deposition and epithelial hyperplasia. Changes in hyaluronin production have also been demonstrated, while mutations in fucosyltransferases reportedly limit asthmatic inflammation.MethodsGiven the importance of glycans in cellular communication and to better characterize tissue glycosylation changes associated with asthma, we performed a comparative glycan analysis of normal and inflamed lungs from a selection of murine asthma models.ResultsWe found that among other changes, the most consistent was an increase in fucose-α1,3-N-acetylglucosamine (Fuc-α1,3-GlcNAc) and fucose-α1,2-galactose (Fuc-α1,2-Gal) motifs. Increases in terminal galactose and N-glycan branching were also seen in some cases, whereas no overall change in O-GalNAc glycans was observed. Increased Muc5AC was found in acute but not chronic models, and only the more human-like triple antigen model yielded increased sulfated galactose motifs. We also found that human A549 airway epithelial cells stimulated in culture showed similar increases in Fuc-α1,2-Gal, terminal galactose (Gal), and sulfated Gal, and this matched transcriptional upregulation of the α1,2-fucosyltransferase Fut2 and the α1,3-fucosyltransferases Fut4 and Fut7.ConclusionsThese data suggest that airway epithelial cells directly respond to allergens by increasing glycan fucosylation, a known modification important for the recruitment of eosinophils and neutrophils

A novel way of liver preservation improves rat liver viability upon reperfusion

Background/aim: Currently, the liver is cold-preserved at 0~4 °C for experimental and clinical purposes. Here, we investigated whether milder hypothermia during the initial phase of the preservation period was beneficial for liver viability upon reperfusion. Methods: In the first set of experiments, rat livers were preserved either conventionally in clinically used histidine-trypthopan-ketoglutarate (HTK) solution (Group A: 45 min and Group B: 24 h) or by slow cooling HTK solution (from 13 °C to 3 °C) during the initial 45 min of preservation (Group C: 24 h). In the second set of experiments, additional groups of livers were evaluated: Group BB—preservation according to Group B and Group CC—preservation according to Group C. Further, some livers were preserved at 13 °C for 24 h. Livers were then reperfused using a blood-free perfusion model. Results: Bile production was approximately 2-fold greater in Group C compared to Group B. Alanine transaminase (ALT) and aspartate transaminase (AST) release into perfusate were 2~3-fold higher in Group B compared to Group C. No significant differences were found in ALT and AST release between Group C and Group A. Livers in Group CC compared to Group BB exhibited significantly lower portal resistance, greater oxygen consumption and bromosulfophthalein excretion into bile and lower lactate dehydrogenase (LDH) release into perfusate. Histological evaluation of tissue sections in Group BB showed parenchymal dystrophy of hepatocytes, while dystrophy of hepatocytes was absent in Group CC. Livers preserved at 13 °C for 24 h exhibited severe ischemic injury. Conclusion: These results suggest that the conventional way of liver preservation is not suitable at least for rat livers and that slow cooling of HTK solution during the initial phase of cold storage can improve liver viability during reperfusion

Preparation of water-in-oil-in-water emulsions by low frequency ultrasound using skim milk and sunflower oil

Double emulsions of water-in-oil-in-water (W1/O/W2) type were prepared in skim milk using 20 kHz ultrasound. Ultrasonic emulsification provides a simple and quick yet effective protocol by which double emulsions can be created using low amounts of surfactant. The fat displacement and shelf stability of the emulsions were found to be dependent on the amount of sonication power delivered during the dispersion of the W1/O emulsion into skim milk. Acoustic intensity was manipulated to control the size distribution of the outer shell of the emulsion droplets to a range similar to that of fat globules in unhomogenized whole milk. The encapsulation yield (proportion of W1/O droplets subsequently encapsulated within the W1/O/W2 double emulsion) varied from 5 to 35%. The variation could be due to coalescence/aggregation of water phase droplets within the initially formed W1/O emulsion. The resultant double emulsion droplets were found to be relatively stable over 7 days. However, a source of instability was found to be the leakage of entrapped aqueous phase from the inner to the outer phase with storage time. Phase separation was primarily observed for double emulsions prepared using high W1/O loading (20% w/w) and low ultrasonic power delivery (<6 W)

Effects of Sizofiran on Endotoxin-Enhanced Cold Ischemia- Reperfusion Injury of the Rat Liver

Summary Kupffer cells (KC), resident macrophages of the liver, have been strongly implicated in lipopolysaccharide (LPS)-induced liver graft injury. However, our recent study showed that sizofiran (schizophyllan glucan) (SPG), which activates KC, did not influence cold ischemia-reperfusion liver injury of LPS-exposed rats. Here we investigated some mechanisms by which SPG does not aggravate LPS-enhanced cold ischemia-reperfusion rat liver injury. Control and SPG-treated rats were exposed to LPS for 2 h prior to hepatectomy. The livers were cold-preserved in University of Wisconsin solution followed by reperfusion with Krebs-Henseleit buffer. We found that SPG dramatically inhibited LPS-induced increases of tumor necrosis factor-α (TNF-α) in the plasma and bile in vivo. Moreover, LPS-induced TNF-α release into the washout solution after cold ischemia was also abrogated by SPG pretreatment. However, SPG increased TNF-α release into the perfusate after reperfusion. On the other hand, SPG completely abolished expression of c-myc protooncogene, which is known to sensitize cells to TNF-α cytotoxicity. In conclusion, inhibition of both TNF-α release after LPS challenge and c-myc expression may explain why activation of KC with SPG does not aggravate endotoxin-enhanced cold ischemia-reperfusion liver injury