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• In acutely ill antipsychotic-free schizophrenia patients: increase of TH2 system cytokine IL-13 (p = 0.039). • Decrease of TH1 system markers sICAM-1 (p = 0.011) and sIL-2R (p = 0.063). • Effect of sIL-2R decrease greater in the FEP subgroup (p = 0.01). • Increase of pro-inflammatory IL-6 not significant (p = 0.052). No group differences in: IL-4, IL-8, TNF-alpha, and IFN-gamma. • Findings support the notion of a TH1/TH2 imbalance particularly in the acute manifestation phase of schizophrenia. There is major evidence for the involvement of immunological processes in the pathophysiology of schizophrenia. Especially alterations of T-cell function and activation of the inflammatory response system appear to be linked to schizophrenia. A mild chronic inflammation process has been proposed and repeated findings of altered serum cytokine levels led to the hypothesis of a TH2 shift or cytokine imbalance in schizophrenia. We investigated serum levels of TH1 and TH2 related cytokines and immune markers in 25 patients suffering an acute schizophrenic episode (all unmedicated, 22 neuroleptica-naïve) at different stages of disorder (18 first episode, FEP; 7 recurrent episode, REP) compared to 25 age and sex matched healthy controls. In patients, we found an increase of the TH2 system cytokine IL-13 (p = 0.039) and a decrease of the TH1 system markers sICAM-1 (p = 0.011) and sIL-2R (p = 0.063, n. s.). Elevation of the pro-inflammatory cytokine IL-6 was not significant (p = 0.052). The effect of sIL-2R decrease was greater in the FEP subgroup (p = 0.01) of patients. We found no group differences in the other investigated immune markers: IL-4, IL-8, TNF-alpha, and Interferon-gamma, in which most readings were below the lower detection limit of the respective assay. Our findings support the notion of a TH1/TH2 imbalance particularly in the acute manifestation phase of schizophrenia. In the long run, this may lead to the identification of cytokine patterns that are applicable as trait or state markers, may be helpful in making or ensuring diagnosis or in monitoring therapy. [ABSTRACT FROM AUTHOR]

Background Oxidative stress and impaired antioxidant defenses are reported in schizophrenia and are associated with disturbed neurodevelopment, brain structural alterations, glutamatergic imbalance, increased negative symptoms, and cognitive impairment. There is evidence that oxidative stress predates the onset of acute psychotic illness. Here, we investigate the effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system (AODS). Method In 64 help-seeking UHR-individuals (13–25 years of age), vitamin E levels and glutathione were investigated before and after 12 weeks of treatment with either 1.2 g/d omega-3 (PUFA-E) or saturated fatty acids (SFA-E), with each condition also containing 30.4 mg/d alpha-tocopherol to ensure absorption without additional oxidative risk. Results In multivariate tests, the effects on the AODS (alpha-tocopherol, total glutathione) were not significantly different ( p =0.13, p =0.11, respectively) between treatment conditions. According to univariate findings, only PUFA-E caused a significant alpha-tocopherol increase, while PUFA-E and SFA-E caused a significant gamma- and delta-tocopherol decrease. Total glutathione (GSHt) was decreased by PUFA-E supplementation. Conclusion Effects of the PUFA-E condition on the vitamin E and glutathione AODS could be mechanisms underlying its clinical effectiveness. In terms of the vitamin E protection system, PUFA-E seems to directly support the antioxidative defense at membrane level. The effect of PUFA-E on GSHt is not yet fully understood, but could reflect antioxidative effects, resulting in decreased demand for glutathione. It is still necessary to further clarify which type of PUFA/antioxidant combination, and in which dose, is effective at each stage of psychotic illness. [ABSTRACT FROM AUTHOR]

Summary Background & aims Reduced epidermal ceramide content may lead to an impaired skin barrier in atopic dermatitis. Plasma concentration of the ceramide precursor sphingomyelin increases after milk-fat consumption due to affected lipoprotein metabolism, although sphingomyelin, a main component of milk phospholipids, might also directly influence plasma sphingomyelin levels. The aim was to determine whether supplementation of a dairy drink with milk phospholipids improves skin parameters and influences plasma lipid profile. Methods In a double-blind cross-over study, 39 patients were randomized into 2 groups and daily received phospholipid milk (3 g phospholipids ≙ 0.75 g sphingomyelin) or normal whole milk as placebo control for 6 weeks. SCORAD indices, serum immune and plasma lipid parameters were determined. Results SCORAD indices did not differ between groups following control and phospholipid milk supplementation (control milk: 10.9 ± 5.9 vs. phospholipid milk: 11.7 ± 6.9, P = 0.416), but were significantly decreased compared to baseline (baseline: 15.6 ± 8.8, P < 0.05). Plasma sphingomyelin proportions were also similar after the treatments (control milk: 27.5 ± 2.3 vs. phospholipid milk: 27.4 ± 2.6% of total phospholipids, P = 0.894), but were significantly increased compared to baseline (20.7 ± 2.4% of total phospholipids, P < 0.05). Conclusions Supplementation of a dairy drink with milk phospholipids has no beneficial effect on skin parameters compared to consumption of whole milk in patients with atopic dermatitis. To elucidate an impact of the plasma sphingomyelin proportion on skin conditions, further studies are necessary. Clinical trial ID: Registered under ClinicalTrials.gov . Identifier no. NCT01326520 . [ABSTRACT FROM AUTHOR]

Ammonium bituminosulfonate preparations have been used for various dermatological diseases since the 19th century. The dark preparation is known as the so-called "drawing salve" (Ichtholan®) for the treatment of abscesses and furuncles. The underlying activity is in part the loosening of the skin, which facilitates pus extraction and treatment of deep inflammations. For this investigation 3D skin models were incubated with ointments containing different ammonium bituminosulfonate concentrations. Histological and immunohistochemical staining as well as penetration investigation were carried out. The effect of dark ammonium bituminosulfonate ointments on skin loosening was investigated to reveal the underlying mechanism. The skin loosening effect could be proved by HE-staining for ammonium bituminosulfonate treated skin models. This effect was concentration dependent. While treatment with ammonium bituminosulfonate ointment had no influence on keratin expression, high concentrated ointments led to decreased filaggrin and laminin expression. Treatment of skin models with ABS ointments led to an increased skin permeability, which was concentration dependent. For the first time the skin loosening effect of ammonium bituminosulfonate ointment has been demonstrated on 3D skin models. This effect is at least in part caused by the interaction of the substance with structure dependent proteins of the epidermis. [Display omitted] [ABSTRACT FROM AUTHOR]

• BDNF heterozygous mice display deficits in the T-maze test. • There is a quadratic association of PLA2 with performance in the open field test. • BDNF deficiency and female sex are associated with elevated plasma PLA2 levels. • PLA2 is significantly correlated with adrenal and body weight. Decreased levels of Brain-Derived Neurotrophic Factor (BDNF) are a common finding in schizophrenia. Another well-documented protein linked to schizophrenia is intracellular Ca2+-independent Phospholipase (PLA2). However, the potential association between PLA2 and BDNF with regard to schizophrenia has yet to be examined. In the present study, male and female BDNF knockout mice, a possible genetic model of schizophrenia, were exposed to prenatal stress and tested in the nest test, open field test and T-maze. Following behavioral tests, whole brain and plasma samples were harvested to measure the activity of PLA2. BDNF knockout mice showed cognitive deficits in the T-maze. Furthermore, there was a quadratic association of PLA2 with performance in the open field test. Moreover, BDNF deficiency and female sex were associated with elevated plasma PLA2 levels. The cognitive impairment of BDNF heterozygous mice as well as their increased PLA2 activity in plasma is consistent with findings in schizophrenia patients. The particular elevation of PLA2 activity in females may partly explain sex differences of clinical symptoms in schizophrenia (e.g. age of onset, severity of symptoms). Additionally, PLA2 was significantly correlated with body and adrenal weight after weaning, whereby the latter emphasizes the possible connection of PLA2 with steroidogenesis. [ABSTRACT FROM AUTHOR]

• The model is suitable for evaluation of bioactivity and biocompatibility of antiseptics. • Damage of skin models due to infection is prevented by incubation with antiseptics. • The model is suitable for investigating mechanism and effectiveness of antimicrobial strategies. • Incubation with polihexanide after infection enhanced the innate immune response. In the light of pandemic spreads of multi-drug-resistant micro-organisms, alternative antimicrobial strategies to the use of antibiotics are the focus of research attention. As a prerequisite for medical application, the aim of this study was to develop a three-dimensional full skin infection model to evaluate the bioactivity and biocompatibility of antiseptics in application-relevant concentrations. A three-dimensional (3D) full skin model consisting of collagen-embedded fibroblasts as dermis and a fully differentiated epidermis built from keratinocytes was infected with Staphylococcus aureus. Infected skin models were treated for 24 h with the antiseptics polihexanide, octenidine dihydrochloride, chlorhexidine digluconate and povidone-iodine. Infection resulted in detrimental effects, a strong immune response with increased secretion of lactate dehydrogenase and pro-inflammatory cytokines, and increased gene expression of pro-inflammatory cytokines and antimicrobial peptides after 24 h. Application of antiseptics protected the skin models from damage due to S. aureus infection while demonstrating good biocompatibility. The best ratio of bioactivity to biocompatibility was observed for polihexanide. Polihexanide also enhanced the innate immune response by increasing the gene expression levels of antimicrobial peptides such as human β-defensin 2, human β-defensin 3, psoriasin and ribonuclease 7. The developed model provides an excellent tool to investigate the response of human cells to microbial infections in a complex 3D structure. Furthermore, the infection model is appropriate for evaluation of bioactivity and biocompatibility of antiseptics. As such, the model presented in this study is a promising approach to evaluate the mechanisms and effectiveness of new antimicrobial strategies. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Adolescence is a period of major brain white matter (WM) changes, and membrane lipid metabolism likely plays a critical role in brain WM myelination. Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential components of cell membranes including oligodendrocytes, and LC-PUFA release and turnover in membranes is regulated by phospholipase A 2 enzymes. To investigate the role of membrane lipid metabolism in healthy WM myelination across adolescence, the present study examined the relationship between membrane LC-PUFA biostatus, phospholipase A 2 activity, and brain WM microstructure in healthy subjects aged 9–20 years ( n = 30). Diffusion tensor imaging (DTI) was performed to measure average fractional anisotropy (FA) and diffusivity (indices sensitive to WM myelination) of nine major cerebral WM tracts. Blood samples were collected to measure erythrocyte membrane fatty acid concentrations and plasma intracellular phospholipase A 2 activity ( in PLA 2 ). Plasma in PLA 2 activity showed a significant U-curved association with WM radial diffusivity, and an inverted U-curved association with WM FA, independent of age. A significant positive linear correlation was observed between docosahexaenoic acid concentration and axial diffusivity in the corpus callosum. These findings suggest that there may be optimal physiological in PLA 2 activity levels associated with healthy WM myelination in late childhood and adolescence. Myelination may be mediated by cleavage of docosahexaenoic acid from membrane phospholipids by in PLA 2 . These findings have implications for our understanding of the role of LC-PUFA homeostasis in myelin-related neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Dermatophytes initiate dermatophytosis, but susceptibility to infection is dictated by host genetic factors, although the role of some of these-such as human beta-defensin 2 (hBD-2) genomic (DEFB4) copy number (CN) variation and its induction by IL-22-remains unclear. This was investigated in this cross-sectional study in 442 unrelated Caucasian subjects, including 195 healthy controls and 247 dermatophytosis patients who were divided into five subgroups according to clinical presentation. DNA samples were evaluated for DEFB4 CN variation by relative quantification using the comparative CT method, and serum hBD-2 and IL-22 levels were determined by ELISA. DEFB4 CN in patients was significantly lower and, except in the tinea cruris subgroup, serum hBD-2 levels were higher than in controls. The positive correlation between hBD-2 levels and DEFB4 CN observed in controls was not detected in patients, who also had higher serum IL-22 levels that were positively correlated with hBD-2 levels. Moreover, unlike in control subjects, the serum IL-22 level was negatively correlated with DEFB4 CN in patients. Taken together, these findings suggest an association between decreased DEFB4 CN, elevated serum hBD-2 and IL-22 levels, and dermatophytosis, underscoring a gene/cytokine interaction in the occurrence of this infection. [ABSTRACT FROM AUTHOR]

Abstract: Antimicrobial effects of substances can be determined with different methods that measure distinct parameters. Thus, a comparison of the results obtained can be difficult. In this study, two in vitro methods were employed to determine concentration and time dependent effects of cyclodextrin (CD)-complexes with the antiseptics chlorhexidine diacetate (CHX), iodine (IOD) and polihexanide (PHMB) on Candida albicans and Malassezia pachydermatis. Using both, microplate laser nephelometry and the ATP bioluminescence assay, it could be shown that CD–antiseptics-complexes tested exhibited significant antifungal effects with the exception of γ–CD–CHX in the case of C. albicans. Microplate laser nephelometry (MLN) is an optical method and enables a quantitative determination of particle concentrations in solution. By means of this method, microbial growth under influence of potential antimicrobial substances can be monitored over a prolonged time period. In addition, the antimicrobial activity was analyzed by measurement of the microbial adenosine triphosphate (ATP) content with a bioluminescent assay. The luminescent signal is directly proportional to the amount of ATP, and thus, a linear function of the number of living microbial cells present. Both methods were compared according to the half maximal inhibitory concentration (IC50) calculated and the statistical evaluation of Pearson''s correlation coefficient (r). In summary, it could be demonstrated that both methods yield similar results although they differ in the parameter. [Copyright &y& Elsevier]

Candida albicans binds and utilizes human complement inhibitors, such as C4b-binding protein (C4BP), Factor H, and FHL-1 for immune evasion. Here, we identify Candida pH-regulated antigen 1 (Pra1) as the first fungal C4BP-binding protein. Recombinant Pra1 binds C4BP, as shown by ELISA and isothermal titration calorimetry, and the Pra1-C4BP interaction is ionic in nature. The Pra1 binding domains within C4BP were localized to the complement control protein domain 4 (CCP4), CCP7, and CCP8. C4BP bound to Pra1 maintains complement-inhibitory activity. C4BP and Factor H bind simultaneously to Candida Pra1 and do not compete for binding at physiological levels. A Pra1-overexpressing C. albicans strain, which had about 2-fold Pra1 levels at the surface acquired also about 2-fold C4BP to the surface, compared with the wild type strain CAI4. A Pra1 knock-out strain showed ~22% reduced C4BP binding. C4BP captured by C. albicans from human serum inhibits C4b and C3b surface deposition and also maintains cofactor activity. In summary, Candida Pra1 represents the first fungal C4BP-binding surface protein. Pra1, via binding to C4BP, mediates human complement control, thereby favoring the immune and complement evasion of C. albicans. [ABSTRACT FROM AUTHOR]

Objective: To compare different staining methods to evaluate human sperm morphology. Design: Prospective study. Setting: Patients at the Departments of Dermatology and Urology, University of Jena, Germany. Patient(s): A total of 94 randomly collected patients attending the andrological outpatient clinics of the Departments of Dermatology and Urology, University of Jena, Germany. Intervention(s): None. Main Outcome Measure(s): Statistical comparison of resultant standard morphological parameters (mean percentages) after staining according to Papanicolaou and Shorr methods and with Testsimplets® prestained slides. Result(s): All morphological parameters investigated (percent normal morphology, percent head, midpiece, and flagellar abnormalities) correlated statistically significantly positively, however with markedly lower correlation coefficients for the Testsimplets®results. As compared with the mean Papanicolaou (4.78% ± 2.54%) and Shorr staining (4.75% ± 2.64%) results, a statistically significantly lower percentage of morphologically normal spermatozoa was determined after using the Testsimplets® slides (3.89% ± 2.53%). In general, the mean values of all parameters differed for all comparisons with the Testsimplets® slides and especially for the percentage of flagellar defects but not between the Papanicolaou and the Shorr staining results. Conclusion(s): The results show an extensive agreement between the Papanicolaou- and Shorr-stained smears, whereas Testsimplets® staining exhibited statistically significant deviations. Because the correct evaluation of sperm morphology is of essence within the scope of assisted reproduction and in andrological diagnostics, the use of rapid staining methods cannot be recommended. [Copyright &y& Elsevier]

Abstract: Exudates from non-healing wounds contain elevated levels of proteolytic enzymes, like elastase from polymorphonuclear granulocytes (PMN elastase), reactive oxygen species (ROS) and reactive nitrogen species (RNS). The overproduction of proteolytic enzymes leads to reduced concentrations of growth factors and proteinase inhibitors, resulting in an imbalance between degradation and remodelling processes. Thus, the reduction of protein-degrading enzymes and scavenging of ROS and RNS seem to be suitable ways to support the healing process of chronic stagnating wounds. The aim of this study was to test selected wound dressings from different biomaterials (collagen, oxidized regenerated cellulose (ORC) and ORC/collagen mixture), regarding their antioxidative potential in vitro and their influence on the concentration and activity of PMN elastase in chronic wound fluid. Antioxidant capacity of the investigated wound dressing was determined by a pholasin-based chemiluminescent assay. PMN elastase concentration was determined by means of ELISA. Enzyme activities could be measured by a fluorescence assay. As the presented data demonstrates, all tested materials showed antioxidant capacity. In addition, the investigated materials were able to reduce the concentration and activity of PMN elastase. Beside other aspects, such as biocompatibility, biodegradability, fluid absorption and clinical effects (e.g. angiogenesis and microcirculation), the understanding of these properties may help to support the further refinement of wound dressings for improved wound healing. [Copyright &y& Elsevier]

A shell-less hen's egg based infection test with Pseudomonas aeruginosa was established to investigate the antimicrobial efficacy of drugs and drug formulations close to the in vivo situation. The test system using preincubated fertilized chicken eggs transferred in petri dishes was optimized with respect to the controlled local application of liquid materials and bacteria as well as the bacterial cultivation conditions. The applicability of the ex ovo infection model was confirmed with antimicrobial susceptibility tests using tobramycin, ciprofloxacin and meropenem. The validity of the ex ovo data was demonstrated by correlation with in vitro data of the CellTiter®-Blue and the microplate laser nephelometry assay. Real-time imaging of the progress of infection and the efficacy of the treatment could be realized by the MolecuLight i:X™ technique. Furthermore, in a proof-of-concept efficacy, biocompatibility and even the presence of irritants were determined side-by-side using commercial ophthalmics. In conclusion, this egg based infection model could bridge the gap between in vitro and in vivo models for the evaluation of antimicrobial susceptibility to reduce animal tests according to the 3R concept. [ABSTRACT FROM AUTHOR]

• Cucurbituril[5] and Cucurbituril[6] show good cell compatibility on HaCaT-keratinocytes. • Treatment of keratinocytes with Cucurbituril[7] causes apoptotic cell death. • None of the tested cucurbiturils triggers hemolysis. • Cucurbiturils have potential as host complexes for dermal applications. Cucurbiturils (CB) are pumpkin-shaped macrocyclic molecules consisting of methylen-bridged glycoluril units. Because of their complexing characteristics, they can be used as drug containers for medical purposes. For future biomedical and dermal application of CB, the investigation of cell compatibility is essential. Little is known about the influence of CB on eukaryotic cells, especially on dermal keratinocytes. The structurally related cyclodextrins are known to induce cell death by apoptosis in HaCaT keratinocytes as well as hemolysis in erythrocytes. To examine cytotoxic effects of different CB. Different cytotoxicity tests were performed on HaCaT keratinocytes and erythrocytes incubated with CB[5], CB[6], and CB[7]. CB[5] and CB[6] did not lead to cytotoxic reactions at high concentrations up to 30 mg/mL whereas incubation with CB[7] triggered apoptosis at a concentration of 3.75 mg/mL. None of the investigated CB caused hemolytic effects on erythrocytes. These results confirm the high potential of CB as host-complexes for biomedical and dermal applications. Image, graphical abstract [ABSTRACT FROM AUTHOR]