Tuning the Porosity of Dextran Microgels with Supramacromolecular Nanogels as Soft Sacrificial Templates.

Hydrogels, as well as colloidal hydrogels (microgels), are important materials for a large variety of applications in the biomedical field. Microgels with a controlled pore size (meso- and macropores) are required for efficient nutrient support, modulation of cell adhesion, removal of metabolic products in cell cultures, and probiotic loading. Common microgel fabrication techniques do not provide sufficient control over pore sizes and geometry. In this work, the natural polysaccharide dextran modified with methacrylate groups is used to synthesize highly monodisperse meso- and macroporous microgels in a size range of 100-150 µm via photo cross-linking in microfluidic droplets. The size of mesopores is varied by the concentration of dextran methacrylate chains in the droplets (50-200 g L-1 ) and the size of macropores is regulated by the integration of pH-degradable supramacromolecular nanogels with diameters of 300 and 700 nm as sacrificial templates. Using permeability assays combined with confocal laser scanning microscopy, it is demonstrated that functional dextran-based microgels with uniform and defined pores could be obtained.

Microgels react to force: mechanical properties, syntheses, and force-activated functions.

Microgels are colloidal polymer networks with high molar mass and properties between rigid particles, flexible macromolecules, and micellar aggregates. Their unique stimuli-responsiveness in conjunction with their colloidal phase behavior render them useful for many applications ranging from engineering to biomedicine. In many scenarios either the microgel's mechanical properties or its interactions with mechanical force play an important role. Here, we firstly explain microgel mechanical properties and how these are measured by atomic force microscopy (AFM), then we equip the reader with the synthetic background to understand how specific architectures and chemical functionalities enable these mechanical properties, and eventually we elucidate how the interaction of force with microgels can lead to the activation of latent functionality. Since the interaction of microgels with force is a multiscale and multidisciplinary subject, we introduce and interconnect the different research areas that contribute to the understanding of this emerging field in this Tutorial Review.

Enzymatic Synthesis of 2-(ß-Galactosyl)-ethyl Methacrylate by ß-Galactosidase from Pyrococcus woesei and Application for Glycopolymer Synthesis and Lectin Studies.

Glycosidases have long been used for the synthesis of glycosides by transglycosylation reactions. Especially glycosidases from hyperthermophilic bacteria are useful for reactions under extreme reaction conditions, e.g., in the presence of organic solvents. We herein report the facile enzymatic synthesis and purification of 2-(ß-galactosyl)-ethyl methacrylate (Gal-EMA) with the recombinant hyperthermostable glycosidase from Pyrococcus woesei in high yields. Optimized reaction conditions resulted in gram-scale synthesis of the galactosylated monomer with 88% transglycosylation yield. The product Gal-EMA was characterized by high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS), nuclear magnetic resonance (NMR) spectroscopy, and infrared (IR) spectroscopy. Gal-EMA was utilized to synthesize sugar-functionalized acrylate polymers with defined amounts of incorporated galactose (0-100%). Analysis of the binding affinity of the lectin RCA120 from Ricinus communis to the glycopolymers using an enzyme-linked lectin assay (ELLA) revealed KD values between 0.24 and 6.2 nM, depending on the amount of incorporated Gal-EMA. The potential of Gal-EMA for the synthesis of acrylate-functionalized glycan oligomers was demonstrated by sequential elongation of the terminal galactose by two glycosyltransferases, resulting in the terminal glycan N-acetyllactosamine (LacNAc) epitope. In conclusion, the enzymatic synthesis of Gal-EMA opens new routes to a series of novel monomeric building blocks for the synthesis of glycan-functionalized polyacrylates.

Infiltration Depth is the Most Relevant Risk Factor for Overall Metastases in Early Esophageal Adenocarcinoma.

BACKGROUND: Research in early esophageal adenocarcinoma focused on prediction of lymph node metastases in order to stratify patients for endoscopic treatment instead of esophagectomy. Although distant metastases were described in rates of up to 13% of patients within a follow-up of 3 years, their prediction has been neglected so far. METHODS: In a secondary analysis, a cohort of 217 patients (53 T1a and 164 T1b) treated by esophagectomy was analyzed for histopathological risk factors. Their ability to predict the combination of lymph node metastases at surgery as well as metachronous locoregional and distant metastases (overall metastatic rate) was assessed by uni- and multivariate logistic regression analysis. RESULTS: Tumor invasion depth was correlated with both lymph node metastases at surgery (τ = 0.141; P = .012), tumor recurrences (τ = 0.152; P = .014), and distant metastases (τ = 0.122; P = 0.04). Multivariate analysis showed an odds ratio of 1.31 (95% CI 1.02-1.67; P = .033) per increasing tumor invasion depth and of 3.5 (95% CI 1.70-6.56; P < .001) for lymphovascular invasion. The pre-planned subgroup analysis in T1b tumors demonstrated an even lower predictive ability of lymphovascular invasion with an odds ratio of 2.5 (95% CI 1.11-5.65; P = 0.028), whereas the predictive effect of sm2 (odds ratio 3.44; 95% CI 1.00-11.9; P = 0.049) and sm3 (odds ratio 3.44; 95% CI 1.00-11.9; P = 0.049) tumor invasion depth was similar. CONCLUSIONS: The present report demonstrates the insufficient risk prediction of histopathologic risk factors for the overall metastatic rate.

The nucleoid-associated protein WHIRLY1 is required for the coordinate assembly of plastid and nucleus-encoded proteins during chloroplast development.

MAIN CONCLUSION: Chloroplasts deficient in the major chloroplast nucleoid-associated protein WHIRLY1 have an enhanced ratio of LHCs to reaction centers, indicating that WHIRLY1 is required for a coordinate assembly of the photosynthetic apparatus during chloroplast development. Chloroplast development was found to be delayed in barley plants with an RNAi-mediated knockdown of WHIRLY1 encoding a major nucleoid-associated protein of chloroplasts. The plastids of WHIRLY1 deficient plants had a reduced ribosome content. Accordingly, plastid-encoded proteins of the photosynthetic apparatus showed delayed accumulation during chloroplast development coinciding with a delayed increase in photosystem II efficiency measured by chlorophyll fluorescence. In contrast, light harvesting complex proteins being encoded in the nucleus had a high abundance as in the wild type. The unbalanced assembly of the proteins of the photosynthetic apparatus in WHIRLY1-deficient plants coincided with the enhanced contents of chlorophyll b and xanthophylls. The lack of coordination was most obvious at the early stages of development. Overaccumulation of LHC proteins in comparison to reaction center proteins at the early stages of chloroplast development did not correlate with enhanced expression levels of the corresponding genes in the nucleus. This work revealed that WHIRLY1 does not influence LHC abundance at the transcriptional level. Rather, WHIRLY1 in association with nucleoids might play a structural role for both the assembly of ribosomes and the complexes of the photosynthetic apparatus.

In vitro and in vivo pharmacokinetic study of a dexamethasone-releasing silicone for cochlear implants.

Cochlear implants have been widely used for patients with profound hearing loss and partial deafness. Residual low-frequency hearing, however, may deteriorate due to insertion trauma and tissue response around the electrode array. The present study investigated in vitro and in vivo release of dexamethasone from silicone used for cochlear implant electrode carriers. The in vitro experiment involved an apparatus simulating the inner ear fluid environment in humans. Release from two sizes of silicone films (200 µm × 1 mm × 10 mm and 500 µm × 1 mm × 10 mm), each loaded with 2 % dexamethasone, and was measured for 24 weeks. In the in vivo experiment, silicone rods loaded with 2 or 10 % dexamethasone, respectively, were implanted into the scala tympani of guinea pigs. Perilymph concentrations were measured during the first week after implantation. The results showed that dexamethasone was released from the silicone in a sustained manner. After a burst release, perilymph concentration was similar for silicone incorporated with 2 and 10 % dexamethasone, respectively. The similar pharmacokinetic profile was found in the in vitro experiment. The period of sustained drug delivery was maintained for 20 weeks in vitro and for 1 week in vivo. The results of the present study suggest that drugs like dexamethasone are released in a controlled manner from silicon electrode carriers of cochlear implants. Further studies will identify optimal release profiles for the use with cochlear implants to improve their safety and long-term performance.

Mechanically Resistant Poly(N-vinylcaprolactam) Microgels with Sacrificial Supramolecular Catechin Hydrogen Bonds.

Microgels (µgels) swiftly undergo structural and functional degradation when they are exposed to shear forces, which potentially limit their applicability in, e.g., biomedicine and engineering. Here, poly(N-vinylcaprolactam) µgels that resist mechanical disruption through supramolecular hydrogen bonds provided by (+)-catechin hydrate (+C) are synthesized. When +C is added to the microgel structure, an increased resistance against shear force exerted by ultrasonication is observed compared to µgels crosslinked by covalent bonds. While covalently crosslinked µgels degrade already after a few seconds, it is found that µgels having both supramolecular interchain interactions and covalent crosslinks show the highest mechanical durability. By the incorporation of optical force probes, it is found that the covalent bonds of the µgels are not stressed beyond their scission threshold and mechanical energy is dissipated by the force-induced reversible dissociation of the sacrificial +C bonds for at least 20 min of ultrasonication. Additionally, +C renders the µgels pH-sensitive and introduces multiresponsivity. The µgels are extensively characterized using Fourier-transform infrared, Raman and quantitative nuclear magnetic resonance spectroscopy, dynamic light scattering, and cryogenic transmission electron microscopy. These results may serve as blueprint for the preparation of many mechanically durable µgels.

Mechanoresponsive diselenide-crosslinked microgels with programmed ultrasound-triggered degradation and radical scavenging ability for protein protection.

In the context of controlled delivery and release, proteins constitute a delicate class of cargo requiring advanced delivery platforms and protection. We here show that mechanoresponsive diselenide-crosslinked microgels undergo controlled ultrasound-triggered degradation in aqueous solution for the release of proteins. Simultaneously, the proteins are protected from chemical and conformational damage by the microgels, which disintegrate to water-soluble polymer chains upon sonication. The degradation process is controlled by the amount of diselenide crosslinks, the temperature, and the sonication amplitude. We demonstrate that the ultrasound-mediated cleavage of diselenide bonds in these microgels facilitates the release and activates latent functionality preventing the oxidation and denaturation of the encapsulated proteins (cytochrome C and myoglobin) opening new application possibilities in the targeted delivery of biomacromolecules.

Virtual Biopsy by Electrical Impedance Spectroscopy in Barrett's Carcinoma.

PURPOSE: Early detection of adenocarcinomas in the esophagus is crucial for achieving curative endoscopic therapy. Targeted biopsies of suspicious lesions, as well as four-quadrant biopsies, represent the current diagnostic standard. However, this procedure is time-consuming, cost-intensive, and examiner-dependent. The aim of this study was to test whether impedance spectroscopy is capable of distinguishing between healthy, premalignant, and malignant lesions. An ex vivo measurement method was developed to examine esophageal lesions using impedance spectroscopy immediately after endoscopic resection. METHODS: After endoscopic resection of suspicious lesions in the esophagus, impedance measurements were performed on resected cork-covered tissue using a measuring head that was developed, with eight gold electrodes, over 10 different measurement settings and with frequencies from 100 Hz to 1 MHz. RESULTS: A total of 105 measurements were performed in 60 patients. A dataset of 400 per investigation and a total of more than 42,000 impedance measurements were therefore collected. Electrical impedance spectroscopy (EIS) was able to detect dysplastic esophageal mucosa with a sensitivity of 81% in Barrett's esophagus. CONCLUSION: In summary, EIS was able to distinguish different tissue characteristics in the different esophageal tissues. EIS thus holds potential for further development of targeted biopsies during surveillance endoscopy. Trial Registration NCT04046601.

Tumor cell identification and classification in esophageal adenocarcinoma specimens by hyperspectral imaging.

Esophageal cancer is the sixth leading cause of cancer-related death worldwide. Histopathological confirmation is a key step in tumor diagnosis. Therefore, simplification in decision-making by discrimination between malignant and non-malignant cells of histological specimens can be provided by combination of new imaging technology and artificial intelligence (AI). In this work, hyperspectral imaging (HSI) data from 95 patients were used to classify three different histopathological features (squamous epithelium cells, esophageal adenocarcinoma (EAC) cells, and tumor stroma cells), based on a multi-layer perceptron with two hidden layers. We achieved an accuracy of 78% for EAC and stroma cells, and 80% for squamous epithelium. HSI combined with machine learning algorithms is a promising and innovative technique, which allows image acquisition beyond Red-Green-Blue (RGB) images. Further method validation and standardization will be necessary, before automated tumor cell identification algorithms can be used in daily clinical practice.

Protection of inner ear function after cochlear implantation: compound action potential measurements after local application of glucocorticoids in the guinea pig cochlea.

BACKGROUND: Cochlear implant users with residual hearing often benefit greatly from simultaneous electric and acoustic stimulation. However, implantation can cause trauma to the inner ear, resulting in poorer hearing postoperatively. We investigated whether a single local injection of glucocorticoids can reduce hearing loss in long-term implanted guinea pigs. METHODS: Three groups of animals underwent bilateral surgery. One ear was implanted with an electrode, and the contralateral ear received a cochleostomy only. A single dose of the glucocorticoids triamcinolone or dexamethasone, or of artificial perilymph was infused into cochleae via cochleostomy. Compound action potentials were measured before and after application and for 3 months postoperatively. Tissue growth was measured as the percentage of the total area of the scala tympani that was obliterated. RESULTS: Ears subjected to cochleostomy only and treated with glucocorticoids demonstrated a mild hearing loss. In the implanted ears, both glucocorticoids preserved hearing at least temporarily. The volume of tissue growth within the scala tympani was not reduced, and there was no relation between the amount of tissue and hearing loss. CONCLUSIONS: Both glucocorticoids show a potential benefit for hearing preservation in implanted ears. Glucocorticoid therapy may be useful to protect residual hearing during cochlear implantation.

Concepts and Solutions of the Digital Teams Platform to Support Mobile Work and Virtual Teams.

New work models have been discussed for several years. Especially in the area of knowledge work, mobile and distributed work provides advantages over presence time at companies: It offers more freedom and flexibility to the employees, reduces travel time, and counteracts a major trend: the exodus from rural areas. However, to provide an optimized digital work environment for distributed teams of knowledge workers, many different aspects must be considered, including social, physical, legal, and technological aspects. In this article, we focus on the technological aspects. Nowadays, a multitude of tools and technologies exist to support the communication of distributed teams, to allow working concurrently on documents, or to support data and document exchange. However, many existing solutions only provide solutions for a specific purpose rather than a sophisticated platform that offers all of these services in an integrated manner and additionally takes care of delivering intelligent and data-driven services in a trustful and ethical way. In the research project "Digital Teams", we aim at developing such a platform as open source. In this article, we provide the basic architecture of our platform and share the main concepts and solutions we are currently implementing, such as our dashboard, data exchange concepts, or authentication and authorization mechanisms.

Structural brain changes in tinnitus: grey matter decrease in auditory and non-auditory brain areas.

Tinnitus, the phantom perception of sound, is a frequent disorder that causes significant morbidity. The pathophysiological mechanisms involved in tinnitus generation are still under exploration. Electrophysiological and functional neuroimaging studies give increasing evidence for abnormal functioning both within the central auditory system and in non-auditory brain areas. However, observed changes show great variability, hence lacking a conclusive picture. Recently, structural alterations in the central nervous system have been detected in tinnitus patients by voxel-based morphometry (VBM). Here we aimed to replicate these findings in an independent study sample. We performed structural MRI scans in 28 tinnitus patients with normal audiometry and used VBM to compare results with a control group, matched for age, sex and hearing status. As major results we found significant grey matter decreases in the tinnitus group in the right inferior colliculus and in the left hippocampus. However, neither changes in the subcallosal area nor in the thalamus as described recently have been observed. Our results underscore that (1.) VBM allows to detect structural alterations in tinnitus patients, which seem to be related to tinnitus pathophysiology. (2.) Both, areas in the auditory and the limbic system are involved giving further evidence for the important role of the limbic system in the pathophysiology of tinnitus. (3.) Even groups with similar clinical characteristics might differ in the underlying neurobiological changes.

Nrf transcription factors in keratinocytes are essential for skin tumor prevention but not for wound healing.

The Nrf2 transcription factor is a key player in the cellular stress response through its regulation of cytoprotective genes. In this study we determined the role of Nrf2-mediated gene expression in keratinocytes for skin development, wound repair, and skin carcinogenesis. To overcome compensation by the related Nrf1 and Nrf3 proteins, we expressed a dominant-negative Nrf2 mutant (dnNrf2) in the epidermis of transgenic mice. The functionality of the transgene product was verified in vivo using mice doubly transgenic for dnNrf2 and an Nrf2-responsive reporter gene. Surprisingly, no abnormalities of the epidermis were observed in dnNrf2-transgenic mice, and even full-thickness skin wounds healed normally. However, the onset, incidence, and multiplicity of chemically induced skin papillomas were strikingly enhanced, whereas the progression to squamous cell carcinomas was unaltered. We provide evidence that the enhanced tumorigenesis results from reduced basal expression of cytoprotective Nrf target genes, leading to accumulation of oxidative damage and reduced carcinogen detoxification. Our results reveal a crucial role of Nrf-mediated gene expression in keratinocytes in the prevention of skin tumors and suggest that activation of Nrf2 in keratinocytes is a promising strategy to prevent carcinogenesis of this highly exposed organ.

Long-Term in vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs.

Glucocorticoids are used intra-operatively in cochlear implant surgeries to reduce the inflammatory reaction caused by insertion trauma and the foreign body response against the electrode carrier after cochlear implantation. To prevent higher systemic concentrations of glucocorticoids that might cause undesirable systemic side effects, the drug should be applied locally. Since rapid clearance of glucocorticoids occurs in the inner ear fluid spaces, sustained application is supposedly more effective in suppressing foreign body and tissue reactions and in preserving neuronal structures. Embedding of the glucocorticoid dexamethasone into the cochlear implant electrode carrier and its continuous release may solve this problem. The aim of the present study was to examine how dexamethasone concentrations in the electrode carrier influence drug levels in the perilymph at different time points. Silicone rods were implanted through a cochleostomy into the basal turn of the scala tympani of guinea pigs. The silicone rods were loaded homogeneously with 0.1, 1, and 10% concentrations of dexamethasone. After implantation, dexamethasone concentrations in perilymph and cochlear tissue were measured at several time points over a period of up to 7 weeks. The kinetic was concentration-dependent and showed an initial burst release in the 10%- and the 1%-dexamethasone-loaded electrode carrier dummies. The 10%-loaded electrode carrier resulted in a more elevated and longer lasting burst release than the 1%-loaded carrier. Following this initial burst release phase, sustained dexamethasone levels of about 60 and 100 ng/ml were observed in the perilymph for the 1 and 10% loaded rods, respectively, during the remainder of the observation time. The 0.1% loaded carrier dummy achieved very low perilymph drug levels of about 0.5 ng/ml. The cochlear tissue drug concentration shows a similar dynamic to the perilymph drug concentration, but only reaches about 0.005-0.05% of the perilymph drug concentration. Dexamethasone can be released from silicone electrode carrier dummies in a controlled and sustained way over a period of several weeks, leading to constant drug concentrations in the scala tympani perilymph. No accumulation of dexamethasone was observed in the cochlear tissue. In consideration of experimental studies using similar drug depots and investigating physiological effects, an effective dose range between 50 and 100 ng/ml after burst release is suggested for the CI insertion trauma model.

Restrictive dermopathy: a rare laminopathy.

BACKGROUND: Restrictive dermopathy (RD) belongs to the laminopathies and mostly shows an autosomal recessive heredity pattern. This rare genetic disorder is lethal for the newborn in the neonatal period. Clinical and pathological findings are distinctive and allow for a specific diagnosis in most cases. Furthermore, polyhydramnios, decreased foetal movement, facial dysmorphisms and arthrogryposis are characteristic of RD. Respiratory insufficiency leads to an early neonatal death. METHODS: We present the case of an affected infant and a review of the previously reported cases in the literature. RESULTS: The infant showed thin, shiny skin with exfoliating desquamation, a small, round and open mouth, low-set ears, a small pinched nose, joint contractures at all four extremities and distinctive pulmonic atelectasis. It died 3 h and 20 min post-partum. Histologically, the skin showed the typical pattern of an RD with the epidermis covered by an exfoliated, hyperkeratotic horn layer, clearly hypoplastic hair follicles and a considerably reduced dermis thickness, although it had a massive subcutaneous adipose tissue. Electron microscopically, the diagnosis was confirmed. CONCLUSIONS: It is important to know about this disease and to distinguish it from others like keratinization malfunctions such as ichtyosis, congenital, developmental and akinesia disturbance, etc., to know the prognosis for the affected newborn and to provide sufficient (genetic) counselling to the families. This disorder is caused by dominant mutations of the LMNA (primary laminopathy) or recessive mutations of the ZMPSTE24 (FACE1) (secondary laminopathy) genes.

Oats in healthy gluten-free and regular diets: A perspective.

During the 20th century, the economic position of oats (Avena sativa L.) decreased strongly in favour of higher yielding crops including winter wheat and maize. Presently, oat represents only ~1.3% of the total world grain production, and its production system is fragmented. Nonetheless, current interest is growing because of recent knowledge on its potential benefits in food, feed and agriculture. This perspective will serve as a further impetus, with special focus on the recently valued advantages of oats in human food and health. Five approved European Food Safety Authority (EFSA) health claims apply to oats. Four relate to the oat-specific soluble fibres, the beta-glucans, and concern the maintenance and reduction of blood cholesterol, better blood glucose balance and increased faecal bulk. The fifth claim concerns the high content of unsaturated fatty acids, especially present in the endosperm, which reduces the risks of heart and vascular diseases. Furthermore, oat starch has a low glycemic index, which is favourable for weight control. Oat-specific polyphenols and avenanthramides have antioxidant and anti-inflammatory properties. Thus, oats can contribute significantly to the presently recommended whole-grain diet. Next to globulins, oats contain a small fraction of prolamin storage proteins, called 'avenins', but at a much lower quantity than gluten proteins in wheat, barley and rye. Oat avenins do not contain any of the known coeliac disease epitopes from gluten of wheat, barley and rye. Long-term food studies confirm the safety of oats for coeliac disease patients and the positive health effects of oat products in a gluten-free diet. These effects are general and independent of oat varieties. In the EU (since 2009), the USA (since 2013) and Canada (since 2015) oat products may be sold as gluten-free provided that any gluten contamination level is below 20ppm. Oats are, however, generally not gluten-free when produced in a conventional production chain, because of regular contamination with wheat, barley or rye. Therefore, establishing a separate gluten-free oat production chain requires controlling all steps in the chain; the strict conditions will be discussed. Genomic tools, including a single nucleotide polymorphism (SNP) marker array and a dense genetic map, have recently been developed and will support marker-assisted breeding. In 2015, the Oat Global initiative emerged enabling a world-wide cooperation starting with a data sharing facility on genotypic, metabolic and phenotypic characteristics. Further, the EU project TRAFOON (Traditional Food Networks) facilitated the transfer of knowledge to small- and medium-sized enterprises (SMEs) to stimulate innovations in oat production, processing, products and marketing, among others with regard to gluten-free. Finally, with focus on counteracting market fragmentation of the global oat market and production chains, interactive innovation strategies between customers (consumers) and companies through co-creation are discussed.

Dynamics of albumin synthesis after major rectal operation.

BACKGROUND: Major abdominal operations were found to be associated with long-lasting metabolic changes, such as accelerated release of stress hormones and carbohydrate turnover. It is unknown currently whether acute changes of hepatic protein metabolism persist in a similar way. We wanted to determine the long-term dynamics of albumin synthesis and its relationship to whole body protein breakdown and albumin concentration after major rectal operations. METHODS: We used stable isotope tracer techniques to determine albumin synthesis and whole body protein breakdown (rate of appearance of leucine, Ra) in postoperative patients about 1 week after low anterior rectal resection and also during convalescence (about 4 months after operation), and in healthy controls. Consecutive blood sampling was carried out during continuous isotope infusion (1-[(13)C]-leucine, 0.16 micromol/kg min). RESULTS: Serum albumin concentrations were close to the lower normal limit in patients early after operation but were comparable to controls in convalescent patients. Simultaneously, albumin synthesis was increased in the early postoperative phase (0.53 +/- 0.0.5%/h) compared with convalescent patients (0.32 +/- 0.04) and controls (0.28 +/- 0.04) (P < .01 each). A significant inverse correlation could be found between plasma albumin concentration and corresponding rates of albumin synthesis. Early after operation patients showed an increased leucine Ra (3.25 +/- 0.23 micromol/kg min) that was greater than that of convalescent patients (2.37 +/- 0.06 micromol/kg min, P < .05). Leucine Ra in both patient groups were greater than the rates in controls (2.01 +/- 0.07 micromol/kg min, P < .01) Albumin synthesis correlated weakly with whole body protein breakdown rate. CONCLUSIONS: Albumin synthesis and total body protein breakdown are increased after major abdominal operation, but albumin synthesis returns to control values only during convalescence. Hypoalbuminemia after rectal operations may be associated with high rates of albumin synthesis and is, therefore, not necessarily an indicator of insufficient hepatic function or poor nutritional status in that particular situation.

Nrf2 transcription factor, a novel target of keratinocyte growth factor action which regulates gene expression and inflammation in the healing skin wound.

Keratinocyte growth factor (KGF) is a potent mitogen for epithelial cells, and it promotes survival of these cells under stress conditions. In a search for KGF-regulated genes in keratinocytes, we identified the gene encoding the transcription factor NF-E2-related factor 2 (Nrf2). Nrf2 is a key player in the cellular stress response. This might be of particular importance during wound healing, where large amounts of reactive oxygen species are produced as a defense against invading bacteria. Therefore, we studied the wound repair process in Nrf2 knockout mice. Interestingly, the expression of various key players involved in wound healing was significantly reduced in early wounds of the Nrf2 knockout animals, and the late phase of repair was characterized by prolonged inflammation. However, these differences in gene expression were not reflected by obvious histological abnormalities. The normal healing rate appears to be at least partially due to an up-regulation of the related transcription factor Nrf3, which was also identified as a target of KGF and which was coexpressed with Nrf2 in the healing skin wound. Taken together, our results reveal novel roles of the KGF-regulated transcription factors Nrf2 and possibly Nrf3 in the control of gene expression and inflammation during cutaneous wound repair.

Impact of intrascalar blood on hearing.

OBJECTIVE/HYPOTHESIS: The objective of this controlled animal study was to evaluate the effects of intrascalar blood on hearing. MATERIAL AND METHODS: Eight guinea pigs underwent intrascalar administration of their own blood in one ear and control solution in the contralateral ear. Solutions were applied through cochleostomy to the scala tympani. Compound action potential (CAP) thresholds were determined before administration and at different intervals for 2 months thereafter. RESULTS: Immediate deterioration of thresholds was seen mainly in the high-frequency range, averaging 27 dB and 20 dB in the study and control groups, respectively. At day 3, threshold shifts recovered in the control group but remained in the low-frequency range in the study group. An extensive recovery was seen in both groups. However, permanent threshold shifts persisted. There was an enhanced shift of thresholds of up to 7 dB in the study group. CONCLUSIONS: Even small amounts of intrascalar blood seem to cause transient and permanent detrimental effects on cochlear function. In procedures involving opening of the otic capsule-like stapes surgery and cochlear implantation with hearing preservation-minimizing surgical blood admixture to intracochlear compartments seems therefore fundamental.