Search Results (14)

Background: Athletes’ skin is exposed to increased microbial challenges due to rigorous physical activity, perspiration, constant “skin-to-skin” contact, frequent showering, use of hygiene products, and environmental factors present in training settings. This study aims to characterize the skin microbiome communities of young wrestlers and kickboxers in comparison with their non-athlete age-peers. Methods: A total of 56 combat sport athletes (30 males and 26 females, mean age ± SD = 18.2 ± 1.5 years) and 25 non-athlete youths (control group: 13 males and 12 females, mean age ± SD = 19.8 ± 1.2 years) voluntarily consented to participate in the study conducted by our research team in 2023 and 2024. The skin microbiome analysis involved standardized sampling, DNA isolation, molecular sequencing, and bioinformatic analysis, thus enabling detailed characterization and comparison of the skin microbial community in contact sports athletes and the control group. Results: Our results revealed notable sexual dimorphism in the skin microbiome composition of youth. Males showed a higher relative abundance of bacterial genera associated with nosocomial infections and respiratory diseases, while females had more skin inflammation- and infection-related genera (relative abundances in males vs. in females: Corynebacterium—12.0 vs. 7.2; Luteimonas—4.4. vs. 1.4; Paracoccus—8.8 vs. 5.0; Psychrobacter—6.3 vs. 4.4; Cutibacterium—6.4 vs. 11.4; Kocuria—1.6 vs. 3.9; Micrococcus—5.8 vs. 8.5; Pseudomonas—1.2 vs. 3.4; Streptococcus 3.3 vs. 6.2). We also found skin microbiome differences between athletes and non-athletes in both sexes: wrestlers, who experience frequent skin-to-skin contact and wear less covering sportswear, had microbiome profiles distinct from both kickboxers and non-athletes (relative abundances in athletes vs. in non-athletes: Psychrobacter—7.3 vs. 0.4; Staphylococcus 9.5 vs. 18.5; predominance of genera by sports type: relative abundance of Cutibacterium and Streptococcus was higher in kickboxers, and relative abundance of Acinetobacter, Enhydrobacter, Micrococcus, and Enhydrobacter was higher in wrestlers). Bacteria linked to skin infections (e.g., Aliterella, Arthrobacter, and Empedobacter) were present in around 30% of wrestlers and kickboxers but were absent in the control group. Conclusions: These results underscore the heightened risk of skin infections in contact sports and highlight the importance of regular microbiome monitoring and hygiene protocols among young athletes. Full article

Atopic dermatitis (AD) is a common inflammatory skin disease, in particular among infants, and is characterized, among other things, by a modification in fatty acid and ceramide composition of the skin’s stratum corneum. Palmitic acid and stearic acid, along with C₁₆-ceramide and 2-hydroxy C₁₆-ceramide, occur strikingly in AD. They coincide with a simultaneous decrease in very long-chain ceramides and ultra-long-chain ceramides, which form the outermost lipid barrier. Ceramides originate from cellular sphingolipid/ceramide metabolism, comprising a well-orchestrated network of enzymes involving various ELOVLs and CerSs in the de novo ceramide synthesis and neutral and acid CERase in degradation. Contrasting changes in long-chain ceramides and very long-chain ceramides in AD can be more clearly explained by the compartmentalization of ceramide synthesis. According to our hypothesis, the origin of increased C₁₆-ceramide and 2-hydroxy C₁₆-ceramide is located in the lysosome. Conversely, the decreased ultra-long-chain and very long-chain ceramides are the result of impaired ELOVL fatty acid elongation. The suggested model’s key elements include the lysosomal aCERase, which has pH-dependent long-chain C₁₆-ceramide synthase activity (revaCERase); the NADPH-activated step-in enzyme ELOVL6 for fatty acid elongation; and the coincidence of impaired ELOVL fatty acid elongation and an elevated lysosomal pH, which is considered to be the trigger for the altered ceramide biosynthesis in the lysosome. To maintain the ELOVL6 fatty acid elongation and the supply of NADPH and ATP to the cell, the polyunsaturated PPARG activator linoleic acid is considered to be one of the most suitable compounds. In the event that the increase in lysosomal pH is triggered by lysosomotropic compounds, compounds that disrupt the transmembrane proton gradient or force the breakdown of lysosomal proton pumps, non-HLA-classified AGEP may result. Full article

From the beginning of public vaccinations until the relaxation of COVID-19 measures, many case reports, case series and case–control studies have been published indicating cutaneous side effects of COVID-19 vaccination. Post-vaccination pustular eruption was reported as well, with a challenging differential diagnosis between pustular psoriasis, AGEP (acute generalized exanthematous pustulosis) and neutrophil pustular eruptions. We report a case of 56-year-old woman presented with acute generalized pustular flare up culminated 5 days after the second dose of BNT162b2(Pfizer) vaccination. She was diagnosed with pustular psoriasis flare and due to the regulating role of IL-1 in pustular psoriasis and in the cytokine storm observed in cases of COVID-19 postvaccination inflammation; we decided to treat the patient with an IL-1 antagonist, subcutaneous anakinra (100 mg daily) along with acitretin. One week later, after anakinra withdrawal, she presented a pustular psoriasis flare and a 7-day anakinra re-administration led to a satisfactory improvement in the skin lesions. We also reviewed the medical literature and found 28 case reports with pustular eruption after the COVID-19 vaccination. We compared the patients reported, regarding sex, age, number of doses, post-vaccination period and vaccine brand, and compared those results with our patient. Finally, as indicated by our case and other cases with similarly treated pustular eruptions. targeted therapy to this cytokine imbalance such as anakinra (IL-1) antagonist can improve the clinical course of the patient. Full article

Acute Localized Exanthematous Pustulosis (ALEP) is a rare skin reaction characterized by the sudden onset of multiple, small, sterile, non-follicular pustules in an erythematous and edematous base succeeding systemic drug administration. ALEP is considered a subtype of Acute Generalized Exanthematous Pustulosis (AGEP), although the exact pathogenic mechanism of the disease remains poorly defined. Numerous drugs have been implicated in the pathogenesis of ALEP, while contact mechanisms have also been reported. Herein, we describe the first case of ALEP attributed to minoxidil in a female patient with androgenetic alopecia. The positivity of patch tests and the topical application of minoxidil proposes a contact-induced hypersensitivity reaction. Identifying new agents—including minoxidil—which serve as inducers of drug-specific T-cell-mediated responses in the clinical spectrum of ALEP, adds further value in understanding the complex, yet unknown, pathophysiological mechanisms of this rare drug hypersensitivity reaction. Full article

Drug hypersensitivity reactions are classified into immediate and delayed types, according to the onset time. In contrast to the immediate type, delayed drug hypersensitivity mainly involves T lymphocyte recognition of the drug antigens and cell activation. The clinical presentations of such hypersensitivity are various and range from mild reactions (e.g., maculopapular exanthema (MPE) and fixed drug eruption (FDE)), to drug-induced liver injury (DILI) and severe cutaneous adverse reactions (SCARs) (e.g., Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP)). The common culprits of delayed drug hypersensitivity include anti-epileptics, antibiotics, anti-gout agents, anti-viral drugs, etc. Delayed drug hypersensitivity is proposed to be initiated by different models of molecular recognition, composed of drug/metabolite antigen and endogenous peptide, HLA presentation, and T cell receptor (TCR) interaction. Increasing the genetic variants of HLA loci and drug metabolic enzymes has been identified to be responsible for delayed drug hypersensitivity. Furthermore, preferential TCR clonotypes, and the activation of cytotoxic proteins/cytokines/chemokines, are also involved in the pathogenesis of delayed drug hypersensitivity. This review provides a summary of the current understanding of the molecular recognition, genetic susceptibility, and immune mediators of delayed drug hypersensitivity. Full article

Sterculia diversifolia, widely distributed in Jordan as an ornamental plant, is a synonoum for Brachychiton populneus. Phytochemical studies examining the volatile chemicals in Sterculia diversifolia leaves are limited, despite the rising demand for their numerous applications. Furthermore, it was only recently that a report described the friendly synthesis of silver nanoparticles (AgNPs) using aqueous extract derived from Brachychiton populneus leaves. Therefore, AgNPs were produced using either aqueous plant extracts (AgWPE) or ethanolic plant extracts (AgEPE), and Shimadzu GC-MS equipment was used to detect volatile compounds in the ethanolic leaf extracts. GC-MS profile of leaf ethanolic extracts of the Jordanian chemotypes of S. diversifolia revealed the existence of major components: (3β)-Lup-20(29)-en-3-ol acetate (30.97%) and 1-octadecyne (24.88). Other compounds are squalene (7.19%), germanicol (6.23), dl-α-tocopherol (5.24), heptacosane (4.41), phytol (3.54) and pentacosane (2.89). According to published studies, these reported chemicals have numerous uses, including as animal feed, vitamin precursors, possible eco-friendly herbicides, antioxidants, and anti-inflammatory agents. Aqueous extracts of S. diversifolia leaves had total phenolic of 5.33 mg GAE/g extract and flavonoid contents of 64.88 mg QE/g extract, respectively. The results indicated the contribution of phenolic and flavonoids to this plant’s anti-inflammatory and antioxidant properties. The reduction in AgNO₃ to AgNPs using S. diversifolia leaf extracts was confirmed by the change in solution color from colorless to dark black. Further characterization was attempted by X-ray diffraction, Malvern zeta-sizer and scanning electron microscope. The efficacy of synthesized Ag nanoparticles using aqueous or ethanolic plant extract of S. diversifolia against the Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus showed appreciable activity at 25 µg/mL concentration compared to the source plant extracts. Full article

Acute generalized exanthematous pustulosis (AGEP) is a rare skin reaction, commonly caused by drugs. Available evidence mostly relies on small studies or case reports. We collected published AGEP case reports and, subsequently, described the patient characteristics, suspect and concomitant drugs, time to onset, disease management, and clinical prognosis. This study included 297 AGEP patients (64.3% women) obtained from 250 published case reports or case series with individual patient data. AGEP affected patients of all ages, but the majority of patients (88.2%) were ≥25 years old. The most frequently reported suspect drugs were anti-infectives for systemic use (36.5%), particularly antibacterials for systemic use (31.0%), and especially beta-lactam antibacterials (18.3%) and macrolides (4.3%). Other frequent suspect drugs were antineoplastics (12.2%), and anti-inflammatory/anti-rheumatic products (5.2%) plus hydroxychloroquine (12.8%). Mean time to onset was 9.1 days (standard deviation SD 13.94). Some patients developed fever (64.3%) and systemic involvement (18.9%), and most patients (76.4%) received pharmacological treatment for AGEP. Seven patients died, although five of them were already critically ill prior to AGEP. In conclusion, antibiotics remain the most common suspected cause of AGEP. While case mortality rate may be up to 2.5%, disentangling the role of AGEP on the fatal outcome from the role of the preexisting health conditions remains challenging. Full article

Acute generalized exanthematous pustulosis (AGEP) is a rare skin adverse drug reaction. The pathophysiology and causative drugs associated with AGEP are poorly understood, with the majority of studies in AGEP focusing on a single-drug-outcome association. We therefore aimed to explore and characterize frequently reported drug combinations associated with AGEP using the WHO pharmacovigilance database VigiBase. In this explorative cross-sectional study of a pharmacovigilance database using a data-driven approach, we assessed individual case safety reports (ICSR) with two or more drugs reported to VigiBase. A total of 2649 ICSRs reported two or more drugs. Cardiovascular drugs, including antithrombotics and beta-blockers, were frequently reported in combination with other drugs, particularly antibiotics. The drug pair of amoxicillin and furosemide was reported in 57 ICSRs (2.2%), with an O/E ratio of 1.3, and the combination of bisoprolol and furosemide was recorded 44 times (1.7%), with an O/E ratio of 5.5. The network analysis identified 10 different communities of varying sizes. The largest cluster primarily consisted of cardiovascular drugs. This data-driven and exploratory study provides the largest real-world assessment of drugs associated with AGEP to date. The results identify a high frequency of cardiovascular drugs, particularly used in combination with antibiotics. Full article

The similarity between pustular psoriasis (PP) and acute generalized exanthematous pustulosis (AGEP) poses problems in the diagnosis and treatment of these two conditions. Significant clinical and histopathologic overlap exists between PP and AGEP. PP is an inflammatory disorder that has numerous clinical subtypes, but all with sterile pustules composed of neutrophils. AGEP is a severe cutaneous adverse reaction that is also characterized by non-follicular sterile pustules. Clinical features that suggest a diagnosis of PP over AGEP include a history of psoriasis and the presence of scaling plaques. Histologically, eosinophilic spongiosis, vacuolar interface dermatitis, and dermal eosinophilia favor a diagnosis of AGEP over PP. Importantly, PP and AGEP vary in clinical course and treatment. PP treatment involves topical steroids, oral retinoids, and systemic immunosuppressants. Newer therapies targeting IL-36, IL-23, IL-1, and PDE-4 have been investigated. The removal of the offending agent is a crucial part of the treatment of AGEP. Full article

Mitochondria are both the primary targets and mediators of ischaemic damage in brain cells. Insufficient oxygen causes reactive oxygen species that damage the mitochondria, leading to the loss of functionality and viability of highly energy-demanding neurons. We have recently found that aqueous (AqEP), polyethylene glycol-aqueous (Pg-AqEP) and ethanolic propolis extracts (EEP) can modulate mitochondria and ROS production in C6 cells of astrocytic origin. The aim of this study was to investigate the effect of the extracts on viability, mitochondrial efficiency and superoxide generation, and inflammatory cytokine release in primary rat cerebellar neuronal-glial cell cultures affected by ischaemia (mimicked by hypoxia +/− deoxyglucose). AqEP and Pg-AqEP (15–60 µg/mL of phenolic compounds, or PC) significantly increased neuronal viability in ischaemia-treated cultures, and this was accompanied by a reduction in mitochondrial superoxide levels. Less extended protection against ischaemia-induced superoxide production and death was exhibited by 2 to 4 µg/mL of PC EEP. Both Pg-AqEP and Ag-EP (but not EEP) significantly protected the cultures from hypoxia-induced elevation of TNF-α, IL-1β and IL-6. Only Pg-AqEP (but not AqEP or EEP) prevented hypoxia-induced loss of the mitochondrial basal and ATP-coupled respiration rate, and significantly increased the mitochondrial respiratory capacity. Summarising, the study revealed that hydrophilic propolis extracts might protect brain cells against ischaemic injury by decreasing the level of mitochondrial superoxide and preventing inflammatory cytokines, and, in the case of Pg-AqEP, by protecting mitochondrial function. Full article

This study is the first to assess redox homeostasis in patients with colorectal cancer (CRC) in respect to histopathological parameters associated with the tumour microenvironment such as tumour budding and inflammatory infiltration. Pro-oxidant enzymes (NADPH oxidase (NOX), xanthine oxidase (XO)), antioxidant barrier (Cu,Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH)), redox status (total antioxidant (TAC)/oxidant status (TOS)) and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG)) were determined in both the normal and cancerous tissue of 29 CRC patients. The activity of NOX (p < 0.01) and XO (p = 0.01), as well as SOD (p < 0.0001), CAT (p < 0.0001) and TAC level (p < 0.01) were significantly higher in tumour tissue than in normal colon mucosa. Oxidative damage products (AGE—p < 0.01, AOPP—p < 0.001, MDA—p < 0.001, 8-OHdG—p < 0.0001) were also higher in cancerous colon tissue. Furthermore, we observed that CAT (p < 0.05) and XO (p < 0.05) activity depends on the intensity of inflammatory infiltration. Oxidative stress index (OSI) (p < 0.05) and MDA (p < 0.01) values were significantly higher in patients with tumour budding (TB) > 5 versus cases with TB < 5. However, OSI level did not differ significantly between cancer and normal tissue. Our results confirm that CRC is associated with enzymatic/non-enzymatic redox imbalance and increased oxidative damage to proteins, lipids and DNA. The determination of these biomarkers could be useful for the evaluation of the tumour progression. Full article

The dispersity of graphene (GE) in the matrix has an important influence on the thermal, mechanical, and electrical properties of its derived composites. In this paper, surface modification with a silane coupling agent and a double injection method were used to improve the dispersity of GE in epoxy resin (EP). The thermal, mechanical, and electrical properties of modified graphene/epoxy resin composites (modified GE/EP) were investigated by the thermogravimetric analysis, a four-probe method, and the tensile and bending strength. The results reveal that these properties of the composites can be improved significantly by using the modified GE as the filler. The surface of the modified GE/EP composite was smooth when the curing temperature was 75 °C. The weight loss of the modified GE/EP composite was lower than that of pure EP. The tensile and bending strength of modified GE/EP-0.07 (0.07 wt % modified GE) reached 74.65 and 106.21 MPa, respectively. In addition, the resistivity of modified GE/EP-0.1 (0.1 wt % modified GE) decreased to 52 Ω·cm, which was lower than that of CB/EP-1 (1 wt % carbon black, 95 Ω·cm) and Ag/EP-50 (50 wt % Ag particles, 102 Ω·cm). It is worth noting that the percolation threshold of the modified GE/EP composites was 0.025 vol % modified GE. These results show that the modified GE/EP composites have a potential application in conductive ink when the modified GE is used as the conductive filler. Full article

Severe cutaneous adverse drug reactions (SCARs) represent life-threatening medical conditions and an appropriate causative diagnosis of these conditions is of the highest importance. Existing in vivo diagnostic methods are risky or are just contraindicated in these patients. Therefore, in vitro tests take on greater significance. In this survey, the studies on in vitro assays in SCARs were identified with a defined searching strategy and strict eligibility criteria. Different methods in the particular clinical manifestations and the groups of drugs were compared in respect to the diagnostic parameters obtained. The lymphocyte transformation test and IFNg-ELISpot (Interferon γ-Enzyme-linked immunospot assay) appeared to have the best evidence currently available. Further diagnostic assays, which are based mostly on distinct mechanisms of SCARs, may outdo previous assays but they still need confirmation in a larger group of patients and in more research centers. Data from pediatric populations and acute generalized exanthematous pustulosis (AGEP) patients are scarce. Some technical issues, limitations, and modifications of routine laboratory methods are also discussed. Full article

Acute generalized exanthematous pustulosis (AGEP) is a severe, usually drug-related reaction, characterized by an acute onset of mainly small non-follicular pustules on an erythematous base and spontaneous resolution usually within two weeks. Systemic involvement occurs in about 20% of cases. The course is mostly benign, and only in rare cases complications lead to life-threatening situations. Recent studies highlight the importance of genetic variations in interleukin-36 receptor antagonist gene (IL-36RN) in the pathogenesis of this disease. The physiopathology of AGEP remains unclear, but an involvement of innate and acquired immune cells together with resident cells (keratinocytes), which recruit and activate neutrophils via production of cytokines/chemokines such as IL-17, IL-36, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNFα) and chemokine (C-X-C motif) ligand 8 (CXCL8)/IL-8, has been postulated. Treatment is based on the removal of the causative drug, supportive care, infection prevention and use of potent topical or systemic steroids. Full article