Biodegradation of Photocatalytic Degradation Products of Sulfonamides: Kinetics and Identification of Intermediates.

Sulfonamides can be effectively removed from wastewater through a photocatalytic process. However, the mineralization achieved by this method is a long-term and expensive process. The effect of shortening the photocatalytic process is the partial degradation and formation of intermediates. The purpose of this study was to evaluate the sensitivity and transformation of photocatalytic reaction intermediates in aerobic biological processes. Sulfadiazine and sulfamethoxazole solutions were used in the study, which were irradiated in the presence of a TiO2-P25 catalyst. The resulting solutions were then aerated after the addition of river water or activated sludge suspension from a commercial wastewater treatment plant. The reaction kinetics were determined and fifteen products of photocatalytic degradation of sulfonamides were identified. Most of these products were further transformed in the presence of activated sludge suspension or in water taken from the river. They may have been decomposed into other organic and inorganic compounds. The formation of biologically inactive acyl derivatives was observed in the biological process. However, compounds that are more toxic to aquatic organisms than the initial drugs can also be formed. After 28 days, the sulfamethoxazole concentration in the presence of activated sludge was reduced by 66 ± 7%. Sulfadiazine was practically non-biodegradable under the conditions used. The presented results confirm the advisability of using photocatalysis as a process preceding biodegradation.

IL-17: a novel player in the pathogenesis of vulvar lichen sclerosus.

Introduction: Vulvar lichen sclerosus (VLS) is a chronic progressive, lymphocyte-mediated inflammatory disease whose pathogenesis is complex and not fully elucidated. Aim: In the current study we have investigated for the first time the expression of interleukin-17 (IL-17) and S100A7 in lesional skin obtained from female individuals with histologically confirmed VLS. Material and methods: In our study we used skin biopsies obtained from female patients with histologically confirmed VLS (n = 20) and skin samples from healthy age- and gender-matched individuals (plastic surgery procedures) (n = 10) serving as controls. The tissue expressions of IL-17 and S100A7 were assessed with an immunohistochemical method. Results: The number of cells showing IL-17 expression was significantly higher in VLS lesional skin as compared to normal skin of healthy controls (p < 0.0001). In VLS lesional skin, IL-17 was expressed in the epidermis and by cells within the inflammatory infiltrate in the upper dermis. The number of cells showing S100A7 expression was significantly higher in VLS lesional skin as compared to normal skin of healthy controls (p < 0.0001). In VLS lesional skin, S100A7 was expressed by suprabasal keratinocytes in epidermis. S100A7 was also expressed by cells within the inflammatory infiltrate in the dermis. Conclusions: The results of our study may suggest the involvement of IL-17 and S100A7 in the pathogenesis of VLS. The better understanding of this disease may lead to the development of novel, effective therapeutic strategies e.g. using well-known biologics IL-17 inhibitors class.

Degradation of veterinary antibiotics by the ozonation process: Product identification and ecotoxicity assessment.

The purpose of the study was to evaluate the effects of using of ozonation to remove antibiotics used, among others, in veterinary medicine, from the aqueous environment. The effect of this process on the degradation, mineralisation and ecotoxicity of aqueous solutions of ampicillin, doxycycline, tylosin, and sulfathiazole was investigated. Microbiological MARA® bioassay and two in silico methods were used for the ecotoxicity assessment. Ozonation was an effective method for the degradation of the antibiotics studied and the reduction in ecotoxicity of the solutions. However, after ozonation, the solutions contained large amounts of organic products, including compounds much less susceptible to ozonation than the initial antibiotics. Structures of 14, 12, 40 and 10 degradation products for ampicillin, doxycycline, tylosin, and sulfathiazole, respectively, were proposed. It was confirmed that ozone plays a greater role than hydroxyl radicals in the degradation of these antibiotics, with the exception of TYL. The use of ozonation to obtain a high degree of mineralisation is unfavourable and it is suggested to combine ozonation with biodegradation. The pre-ozonation will cause decomposition of antibiotic pharmacophores, which significantly reduces the risk of spread of antimicrobial resistance in the active biocenosis of wastewater treatment plants.

"Tattoo Characteristics and Testing for Body Dysmorphic Disorder: An Internet-based Self-questionnaire Survey of 4,809 Individuals with Tattoos".

Tattoos have become very popular worldwide in recent years. The aim of this study was to analyse a group of people interested in having tattoos, and screen them for body image disturbances. This cross-sectional self-administered internet-based survey included 4,809 individuals interesting in having tattoos. The majority of the study population were female (79.1%). The survey was conducted using a self-created questionnaire and the Body Dysmorphic Disorder Questionnaire - Dermatology version. Most tattoos in the study group were located on the forearms and hands (28.1%). The most popular motifs were plants (17.5%) and animals (16.9%). Out of 4,809 individuals, 19.9% had problems with acceptance of some parts of their body and 9.8% were screened for body dysmorphic disorder with the Body Dysmorphic Disorder Questionnaire - Dermatology version. Four percent of individuals reported that tattoos helped to improve their own perception of the appearance of their body by distracting attention from the other problems. Limitations of this study include possible participant selection bias and the overrepresentation of women. In conclusion, clinicians may expect to see more patients with tattoos and, of these, approximately 10% may be screened for body dysmorphic disorder.

Efficacy and Safety of Candidate Biosimilar CT-P43 Versus Originator Ustekinumab in Moderate to Severe Plaque Psoriasis: 28-Week Results of a Randomised, Active-Controlled, Double-Blind, Phase III Study.

BACKGROUND: CT-P43 is a candidate ustekinumab biosimilar in clinical development. OBJECTIVES: This paper aims to demonstrate equivalent efficacy of CT-P43 to originator ustekinumab in adults with moderate to severe plaque psoriasis. METHODS: This double-blind, phase III trial randomised patients (1:1) to receive subcutaneous CT-P43 or originator ustekinumab (45/90 mg for patients with baseline body weight ≤ 100 kg/> 100 kg) at week 0 and week 4 in Treatment Period I. Prior to week 16 dosing in Treatment Period II, patients receiving originator ustekinumab were re-randomised (1:1) to continue originator ustekinumab or switch to CT-P43; patients initially randomised to CT-P43 continued receiving CT-P43 (at weeks 16, 28 and 40). The primary endpoint of the trial was mean per cent improvement from baseline in Psoriasis Area Severity Index (PASI) score at week 12. Equivalence was concluded if confidence intervals (CIs) for the estimate of treatment difference were within pre-defined equivalence margins: ± 10% [90% CI; modified intent-to-treat set; Food and Drug Administration (FDA) approach] or ± 15% [95% CI; full analysis set for patients only receiving 45 mg doses in Treatment Period I; European Medicines Agency (EMA) approach]. Additional efficacy, pharmacokinetic, safety and immunogenicity endpoints were evaluated through week 52. Results to week 28 are reported here. RESULTS: In Treatment Period I, 509 patients were randomised (CT-P43: N = 256; originator ustekinumab: N = 253). The mean per cent improvement in PASI score at week12 was 77.93% and 75.89% for CT-P43 and originator ustekinumab, respectively (FDA approach); per the EMA approach, corresponding values were 78.26% and 77.33%. Estimated treatment differences were 2.05 (90% CI -0.23, 4.32) and 0.94 (95% CI -2.29, 4.16); equivalence was achieved for both sets of assumptions. Further efficacy parameters and pharmacokinetic, safety and immunogenicity outcomes were comparable between treatment groups, including after switching from originator ustekinumab to CT-P43. CONCLUSIONS: CT-P43 demonstrated equivalent efficacy to originator ustekinumab in patients with moderate to severe plaque psoriasis, with comparable pharmacokinetic, safety and immunogenicity profiles. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04673786; date of registration: 17 December, 2020.

Degradation of veterinary antibiotics by Fenton process: Products identification and toxicity assessment.

The aim of the work was primarily to determine the relationship between the doses of Fenton's reagents and the effectiveness of the ecotoxicity removal of aqueous solutions containing selected antibiotics. The degradation process of ampicillin, doxycycline, and tylosin in an acidic environment in the presence of H2O2 and FeSO4 was studied. The effect of reagent doses on the degree of degradation and identification of antibiotic transformation products was measured by the UPLC qTOF method. The degree of mineralisation was determined based on changes in the concentration of total organic carbon. The ecotoxicity of products was determined with commercial MARA® and MICROTOX® bioassays, as well as against unselected microorganisms from polluted rivers and wastewater treatment plant effluent. It was found that the complete degradation of antibiotics and the simultaneous elimination of the toxicity of the Fenton process products required the use of a precisely defined amount of reagents. When an insufficient dose of reactants was used, the post-reaction solutions contained antibiotic derivatives showing antimicrobial activity. On the other hand, the toxicity of the post-reaction solution against to microbiocenoses was observed when too high doses of H2O2 were used in the process. This effect resulted from the presence of unreacted reagent or other unidentified peroxides.

Body Dysmorphic Disorder Questionnaire-Dermatology Version (BDD-DV): formation and validation of the Polish language version.

Introduction: Body dysmorphic disorder (BDD) is a mental health condition defined by preoccupation with a non-existent or minimal flaw (defect) in appearance. This preoccupation causes significant social and occupational impairment, lot of distress and is not better accounted for by another mental disorder. The defect often regards the skin, face or body build. Data show that 8-14% of dermatological patients suffer from BDD, whereas in the cosmetic dermatology setting the incidence is reported as high as 8-37%. The Body Dysmorphic Disorder Questionnaire-Dermatology version (BDDQ-DV) is a screening tool that may help to diagnose patients with BDD in dermatology settings. The questionnaire is self-reported, therefore it can be used in daily dermatology practice. Aim: To create and validate the Polish language version of the BDDQ-DV. Material and methods: The Polish version of BDDQ-DV was created in accordance with international standards. To assess reliability of the questionnaire the Cronbach's α coefficient was used. The reproducibility (test-retest reliability) of the Polish language version of the questionnaire was evaluated using the interclass correlation coefficient (ICC) coefficient. Results: The Polish version of BDDQ-DV was created. The Cronbach's α coefficient based on the first completion of the questionnaire was 0.92 indicating a correspondingly high internal consistency between the questions of the questionnaire. ICC was assessed at 0.998, which indicates excellent reliability. Conclusions: The Polish version of BDDQ-DV may help to identify patients with BDD among Polish-speaking individuals.

Towards Symmetric Thioamides: Microwave-Aided Synthesis of Terephthalic Acid Derivatives.

The multistep synthesis of novel bis-terephthalthioamides based on methyl esters of amino acids (AAs) was proposed using conventional heating and microwave-assisted approaches. In fact, the comparative case study on the thionation of new symmetrical diamides with Lawesson's reagent (LR) was performed. The microwave-accelerated small-scale methodology was successfully employed on the whole pathway from substrates (Gly, Ala, Val, Tyr, Ser) to products (symmetrical dithioamides of terephthalic acid), resulting in significantly reduced reaction time, energy requirements, and slightly increased reaction yields when compared to conventional heating. Moreover, the intermolecular similarity of novel terephthalic acid derivatives was estimated in the multidimensional space (mDS) of the structure/property-related in silico descriptors using principal component analysis (PCA) and hierarchical clustering analysis (HCA). The distance-oriented structure/property distribution was also correlated with the experimental lipophilic data.

Degradation of the Selected Antibiotic in an Aqueous Solution by the Fenton Process: Kinetics, Products and Ecotoxicity.

Sulfonamides used in veterinary medicine can be degraded via the Fenton processes. In the premise, the process should also remove the antimicrobial activity of wastewater containing antibiotics. The kinetics of sulfathiazole degradation and identification of the degradation products were investigated in the experiments. In addition, their toxicity against Vibrio fischeri, the MARA® assay, and unselected microorganisms from a wastewater treatment plant and the river was evaluated. It was found that in the Fenton process, the sulfathiazole degradation was described by the following kinetic equation: r0 = k CSTZ-1 or 0 CFe(II)3 CH2O20 or 1 CTOC-2, where r0 is the initial reaction rate, k is the reaction rate constant, C is the concentration of sulfathiazole, Fe(II) ions, hydrogen peroxide and total organic carbon, respectively. The reaction efficiency and the useful pH range (up to pH 5) could be increased by UVa irradiation of the reaction mixture. Eighteen organic degradation products of sulfathiazole were detected and identified, and a possible degradation mechanism was proposed. An increase in the H2O2 dose, to obtain a high degree of mineralization of sulfonamide, resulted in an increase in the ecotoxicity of the post-reaction mixture.

Influence of pH on the Kinetics and Products of Photocatalytic Degradation of Sulfonamides in Aqueous Solutions.

The aims of the study were to determine the kinetics of the photocatalytic degradation of six sulfonamides in the presence of TiO2-P25 in acidic, neutral, and alkaline solutions and to identify the structures of the stable products. It was stated that the pH of the solution significantly affected the photocatalytic degradation rate of sulfonamides in acidic and alkaline environments, and the effect likely depended on the susceptibility of sulfonamides to attack by hydroxyl radicals. In the post-reaction mixture, we identified the compounds resulting from the substitution of the aromatic rings with a hydroxyl group; the amide hydrolysis products; the hydroxylamine-, azo, and nitro derivatives; and the compounds formed via the elimination of the sulfone group. Moreover, previously unknown azo compounds were detected. Some degradation products of sulfonamides may exhibit marked bacteriostatic activity and high phytotoxicity. The azo and nitro compounds formed in an acidic environment may be potentially more toxic to aquatic ecosystems than the initial compounds.

Increased Serum Levels of S100A4 and S100A15 in Individuals Suffering from Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Recently, some S100 proteins have been suggested to play an important role in the pathogenesis of chronic immune-mediated inflammatory diseases and they may constitute valuable biomarkers for these diseases' diagnosis and monitoring. The objective of the current study was to investigate, for the first time, serum levels of S100A4 and S100A15 in individuals suffering from HS. Furthermore, we assessed the associations between S100A4 and S100A15 serum levels and the severity of disease, CRP serum concentration and some demographic and clinical data. Serum levels of S100A4 and S100A15 were evaluated with the commercially available ELISA kit according to the manufacturer's instructions. The serum level of S100A4 in individuals with HS was significantly elevated as compared to controls, with the highest level found in the individuals in Hurley stage II. The S100A15 serum level was positively correlated with the CRP concentration and was associated with the severity of the disease. The serum level of S100A15 in the individuals in Hurley stage III was significantly elevated compared to that of the controls and the individuals with HS in Hurley stages I and II. S100A4 and S100A15 may be considered as new serum biomarkers for the monitoring of HS progression, and they may play a role in the pathogenesis of HS by promoting inflammatory process and fibrosis.

A New Mechanism of the Selective Photodegradation of Antibiotics in the Catalytic System Containing TiO2 and the Inorganic Cations.

The mechanism of sulfisoxazole (SFF) selective removal by photocatalysis in the presence of titanium (IV) oxide (TiO2) and iron (III) chloride (FeCl3) was explained and the kinetics and degradation pathways of SFF and other antibiotics were compared. The effects of selected inorganic ions, oxygen conditions, pH, sorption processes and formation of coordination compounds on the photocatalytic process in the presence of TiO2 were also determined. The Fe3+ compounds added to the irradiated sulfonamide (SN) solution underwent surface sorption on TiO2 particles and act as acceptors of excited electrons. Most likely, the SFF degradation is also intensified by organic radicals or cation organic radicals. These radicals can be initially generated by reaction with electron holes, hydroxyl radicals and as a result of electron transfer mediated by iron ions and then participate in propagation processes. The high sensitivity of SFF to decomposition caused by organic radicals is associated with the steric effect and the high bond polarity of the amide substituent.

Immunohistochemical analysis of the expression of selected cell lineage markers (CD4, CD8, CD68, c-Kit, Foxp3, CD56, CD20) in cutaneous variant of lichen planus.

BACKGROUND: Lichen planus (LP) is considered to be an immune-mediated disease of a not fully understood etiology. There are scarce data on the immune cells forming the band-like infiltration in cutaneous LP (CLP). The objective of the current study was to investigate the immunohistochemical pattern of cells forming the infiltrate in CLP by assessing the immunoexpression of selected cell lineage markers. METHODS: The immunohistochemical analysis of the expression of CD4, CD8, CD20, CD56, CD68, c-Kit, and Foxp3 was performed in formalin-fixed paraffin-embedded (FFPE) biopsy specimens from 14 cases of CLP and 11 healthy volunteers. RESULTS: The expression of CD4 (P < 0.001), CD8 (P < 0.001), CD68 (P < 0.001), Foxp3 (P < 0.001), CD56 (v = 0.019), and CD20 (P < 0.001) was significantly higher in lesional skin in CLP compared to healthy controls. The ratio of CD4+ to CD8+ cells in the infiltrate was 1.75:1. The expression of Foxp3, CD56, and CD20 was markedly lower than the expression of CD4 and CD8. There was no statistically significant difference in c-Kit expression between CLP lesions and healthy skin (P = 0.57). CONCLUSIONS: We found a wide variety of immune cells in the inflammatory infiltrate in CLP. The expression of CD4, CD8, CD68, Foxp3, CD56, and CD20 was significantly increased in CLP, while the expression of c-Kit was comparable in lesional skin and controls. The presence of various cell populations, including T regulatory cells, NK cells, and B cells, may indicate a complex pathogenesis of CLP.

Serum Concentration and Skin Expression of S100A7 (Psoriasin) in Patients Suffering from Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. An important role of innate immune dysregulation in the pathogenesis of HS has been highlighted. S100A7 (psoriasin) is an innate, antimicrobial protein that exerts proinflammatory and chemotactic action. OBJECTIVES: The objective of the study was to investigate serum concentrations of S100A7 in individuals with HS as compared to healthy controls. Further, we evaluated the expression of S100A7 in lesional HS skin as compared to perilesional (clinically uninvolved) HS skin and normal skin. METHODS: Serum concentrations of S100A7 were evaluated with a commercially available ELISA kit. The expression of S100A7 in the skin was assessed using qRT-PCR and immunofluorescence staining. RESULTS: We found increased expression of S100A7 in lesional HS skin as compared to perilesional HS skin (p = 0.0017). The expression of S100A7 in lesional HS skin was positively associated with serum C-reactive protein concentration and the severity of disease according to Hurley staging. The serum concentration of S100A7 in individuals with HS was decreased as compared to healthy controls and patients with psoriasis. CONCLUSIONS: Upregulated in lesional HS skin, S100A7 may enhance the inflammatory process and contribute to the HS pathogenesis.

The remediation of sulfonamides from the environment by Pleurotus eryngii mycelium. Efficiency, products and mechanisms of mycodegradation.

The objective of the study was to assess the applicability of the mycelium obtained from the in vitro cultures of nontoxic bracket fungus, Pleurotus eryngii, to sulfonamides mycodegradation. Samples containing one of the six selected sulfonamides, sulfanilamide derivatives, were incubated with the mycelium of P. eryngii for 7 and 14 days in vitro. Subsequently, change in the sulfonamide concentration was assessed in the samples using the UPLC-QTof. The transformation products were identified based on monoisotopic molecular mass and fragmentation spectra. The studied sulfonamides did not inhibit the growth of P. eryngii mycelium in the in vitro cultures. In addition, a considerable reduction of sulfonamide concentration was observed in all the incubated samples (from 73.7 ± 8.3% to 99.8 ± 0.3%). In the case of three sulfonamides, the reduction in concentration >90% occurred after 7 days of incubation. However, the transformation of sulfonamides was partially caused by their degradation to simpler organic compounds. After incubation, the products of condensation of sulfonamides with formyl, acyl, and sugar groups, and amino acid-derived compounds were identified in the samples. This indicated the partially reversible nature of the mycodegradation process.