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Summary: Background: Peeling skin syndrome type 1 (PSS1) is a rare and severe autosomal recessive form of congenital ichthyosis. Patients are affected by pronounced erythroderma accompanied by pruritus and superficial generalized peeling of the skin. The disease is caused by nonsense mutations or complete deletion of the CDSN gene encoding for corneodesmosin (CDSN). PSS1 severely impairs quality of life and therapeutic approaches are totally unsatisfactory. Objectives: The objective of this study was to develop the first steps towards a specific protein replacement therapy for CDSN deficiency. Using this approach, we aimed to restore the lack of CDSN and improve cell–cell cohesion in the transition area of the stratum granulosum (SG) to the stratum corneum. Methods: Human CDSN was recombinantly expressed in Escherichia coli. A liposome‐based carrier system, prepared with a cationic lipopeptide to mediate the transport to the outer membrane of keratinocytes, was developed. This formulation was chosen for CDSN delivery into the skin. The liposomal carrier system was characterized with respect to size, stability and toxicity. Furthermore, the interaction with primary keratinocytes and human epidermal equivalents was investigated. Results: The liposomes showed an accumulation at the membranes of keratinocytes. CDSN‐deficient epidermal equivalents that were treated with liposomal encapsulated CDSN demonstrated presence of CDSN in the SG. Finally, the penetration assay and histological examinations revealed an improved epidermal integrity for CDSN‐deficient epidermal equivalents, if they were treated with liposomal encapsulated CDSN. Conclusions: This study presents the first preclinical in vitro experiments for a future specific protein replacement therapy for patients affected by PSS1. What is already known about this topic?Peeling skin syndrome type 1 (PSS1) refers to Mendelian disorders of cornification and is characterized by pruritus, pronounced erythroderma with skin abnormalities and lifelong patchy peeling of the skin.The disease is caused by autosomal recessive nonsense mutations in the gene encoding corneodesmosin (CDSN). Histopathologically, the absence of CDSN is characterized by subcorneal splitting and enhanced detachment of corneocytes. What does this study add?We present a liposomal formulation, which can be used for topical delivery of recombinant CDSN.Our in vitro study shows that the impaired barrier of CDSN‐deficient human epidermal equivalents can be improved when treated with liposomal human CDSN. What is the translational message?This study presents, for the first time, preclinical in vitro experiments for a specific protein replacement therapy in patients with PSS1. Linked Comment: Schmuth. Br J Dermatol 2021; 184:998–999. [ABSTRACT FROM AUTHOR]

Corrosion and dissolution reactions of Na2O.xSiO2 glasses (x=2·0, 2·5, and 3·3) were investigated by static and dynamic corrosion tests at pH values between 7 and 14 and temperatures of 30 and 50°C. The investigated glass compositions are close to those used for water glass production. Several types of leachants with varied pH and SiO2 concentrations were applied to induce corrosion effects. One characteristic feature of the corrosion process is the development of a reaction layer on top of the corroding glasses, a process depending on leachant pH. At intermediate pH values reaction layers were observed, but not at high pH values (>12). To generate altered glass surfaces with and without reaction layers sodium silicate glasses were corroded in deionized H2O, 0·1 M NaOH, and diluted liquid sodium water glasses. The resulting samples or layer materials were investigated by scanning electron microscopy, Raman microscopy, infrared spectroscopy, or 29Si-MAS-NMR spectroscopy. Especially Raman microscopy was applied to characterize depth profiles of structural changes of silicate (Qn) groups and of concentration profiles of molecular H2O within reaction layers. The results are discussed with respect to influences of pH and leachant composition in order to evaluate possible corrosion mechanisms. [ABSTRACT FROM AUTHOR]

The corrosion and dissolution of Na2O.xSiO2 glasses (x=2·0, 2·5, and 3·3) was investigated by static and dynamic corrosion tests at pH values between 7 and 14 with a focus on saturation effects. The corrosion temperatures were 30 and 50°C. The investigated glass compositions are close to those used for water glass production. Two types of leachants with varied concentrations have been applied to study saturation effects. The first type was deionized H2O enriched with up to 2·5 mM SiO2 by dispersing and equilibrating pyrogenic silica. The second type of leachants were liquid sodium water glasses with increasing concentrations and a SiO2:Na2O ratio similar to the dissolving glasses forming dilution series. Two different saturation effects which influence corrosion kinetics were recognised: first, the enrichment of deionised H2O with pyrogenic silica reduced the dissolution rate of reaction layers. An extrapolation of mass loss rates yielded silica saturation levels of 2·8 to 3·8 mM SiO2. Second, the dilution series of sodium water glasses demonstrated the shielding of glass surfaces when pH conditions hindered reaction layer formation. The corrosion rates of a sodium silicate glass with a molar ratio SiO2:Na2O=2·0 were reduced but the respective corrosion rates of a sodium silicate glass with a molar ratio SiO2:Na2O=3·3 were increased with increasing sodium water glass concentration of the initial leachants. The sodium silicate glass with a molar ratio SiO2:Na2O=2·5 showed first an increase and at higher sodium water glass concentrations a decrease of the corrosion rate with increasing concentration of the liquid sodium water glass and thus displayed an intermediate dependence on water glass concentration. [ABSTRACT FROM AUTHOR]

One basic process for the production of liquid sodium water glasses is the dissolution of sodium silicate glasses which can be regarded as an extreme case of glass corrosion. The dissolution processes occur at high pH values and achieve highly concentrated liquid sodium water glasses. To better understand the dissolution process, the methods of glass corrosion studies were adapted and applied. The corrosion and dissolution of Na2O.xSiO2 glasses (x=2·0, 2·5, and 3·3) was investigated by static and dynamic corrosion tests at pH values between 7 and 14. The corrosion temperatures were 30 and 50°C. The investigated glass compositions are close to those used for water glass production. The corrosion of sodium silicate glasses generally follows linear time laws at short corrosion times. The release rates of Na2O and SiO2 are correlated with the glass composition and to the thermodynamics of glass hydrolysis. Two distinct pH regimes exist. Between pH 7 and a certain pH value between 11 and 13 (depends on glass composition and corrosion temperature) the corrosion rate increases slightly with pH and the glasses develop extensive reaction layers. Generally, published corrosion models predict such a rate increase, but at a higher extent than observed here. Above a pH of 11 to 13 the corrosion rates decline with pH by a factor up to 100 and the glasses develop almost no reaction layer. A possible explanation of the rate decrease at higher pH is the shielding of the silicate surface by alkalis. The shielding effect increases with alkali concentration. The pH dependence of reaction layer formation is discussed in terms of solubility or diffusion through a boundary layer with pH and silica concentration gradients in the leachate near the glass surface. [ABSTRACT FROM AUTHOR]

The influence of experimental parameters on the dissolution of sodium silicate glasses with SiO2:Na2O ratios of 2·0 and 3·3 has been investigated in order to establish reliable corrosion conditions. Two principal experimental setups were tested; static (without exchange of leachant) and dynamic (with leachants continuously flowing through). Deionized water and 0·1 M NaOH were used as initial leachants. Surface pretreatment, temperature and time of corrosion, flow rate, surface area to solution volume ratio were varied and optimized. Balancing of glass samples and chemical analysis of leachates were used to describe the dissolution kinetics. Etching with HF was proven to be a reliable surface pretreatment. The chosen optimized corrosion conditions were temperatures of 30 and 50°C, flow rates of 2 l/d, and surface area to solution ratios of 10 m-1. [ABSTRACT FROM AUTHOR]

Contents Antibiotics are of great importance for the preservation of ejaculates for livestock breading. The use of antibiotics, however, is not an appropriate compensation for a lack of hygiene standards in artificial insemination ( AI) centres. Sophisticated hygiene management and the proper identification of hygienic critical control points ( HCCPs) at AI centres provide the basis for counteracting the development of antibiotic resistance in contaminant bacteria and their settlement in AI centres. In recent years, efforts have been made to use antimicrobial peptides ( AMPs) in the preservation of boar semen. Investigations have included the testing of synthetic magainin derivatives and cyclic hexapeptides. One prerequisite for the application of AMPs is that they have a minor impact on eukaryotic cells. Bacterial selectivity, proteolytic stability, thermodynamic resistance, and mechanisms including synergistic interaction with conventional antibiotics have made cyclic hexapeptides highly promising candidates for potential application as peptide antibiotics for semen preservation. [ABSTRACT FROM AUTHOR]

Many antimicrobial peptides bear arginine (R)- and tryptophan (W)-rich sequence motifs. Based on the sequence Ac-RRWWRF-NH2, sets of linear and cyclic peptides were generated by changes in the amino acid sequence,l-d-amino acid exchange and naphthylalanine substituted for tryptophan. Linear RW-peptides displayed moderate activity towards Gram-positiveBacillus subtilis(15 < MIC < 31 μm) and were inactive against Gram-negativeEscherichia coliat peptide concentrations<100 μm. Cyclization induced high antimicrobial activity. The effect of cyclization was most pronounced for peptides with three adjacent aromatic residues. Incorporation ofd-amino acid residues had minor influence on the biological activity. The haemolytic activity of all RW-peptides at 100 μmconcentration was low (<7% lysis for linear R/W-rich peptides and<28% for the cyclic analogues). Introduction of naphthylalanine enhanced the biological activities of both the linear and cyclic peptides. All peptides induced permeabilization of large unilamellar vesicles (LUVs) composed of lipids of the membrane ofB. subtilisand erythrocytes, but surprisingly had no effect on LUVs composed of lipids of theE. coliinner membrane. The profiles of peptide activity againstB. subtilisand red blood cells correlated with the permeabilizing effects on the corresponding model membranes and were related to hydrophobicity parameters as derived from reversed phase high-performance liquid chromatography (HPLC). The results underlined the importance of amphipathicity as a driving force for cell lytic activity and suggest that conformational constraints and an appropriate position of aromatic residues allowing the formation of hydrophobic clusters are highly favourable for antimicrobial activity and selectivity. [ABSTRACT FROM AUTHOR]