Dose‐ and time‐dependent effects of triethylene glycol dimethacrylate on the proteome of human THP‐1 monocytes

Triethylene glycol dimethacrylate (TEGDMA) is commonly used in polymer resin‐based dental materials. This study investigated the molecular mechanisms of TEGDMA toxicity by identifying its time‐ and dose‐dependent effects on the proteome of human THP‐1 monocytes. The effects of different concentrations (0.07–5 mM) and exposure times (0–72 h) of TEGDMA on cell viability, proliferation, and morphology were determined using a real‐time viability assay, automated cell counting, and electron microscopy, and laid the fundament for choice of exposure scenarios in the proteomic experiments. Solvents were not used, as TEGDMA is soluble in cell culture medium (determined by photon correlation spectroscopy). Cells were metabolically labeled [using the stable isotope labeled amino acids in cell culture (SILAC) strategy], and exposed to 0, 0.3 or 2.5 mM TEGDMA for 6 or 16 h before liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) analyses. Regulated proteins were analyzed in the STRING database. Cells exposed to 0.3 mM TEGDMA showed increased viability and time‐dependent upregulation of proteins associated with stress/oxidative stress, autophagy, and cytoprotective functions. Cells exposed to 2.5 mM TEGDMA showed diminished viability and a protein expression profile associated with oxidative stress, DNA damage, mitochondrial dysfunction, and cell cycle inhibition. Altered expression of immune genes was observed in both groups. The study provides novel knowledge about TEGDMA toxicity at the proteomic level. Of note, even low doses of TEGDMA induced a substantial cellular response.     

Very low dose isotretinoin is effective in controlling seborrhea

Background: Excessive seborrhea, coarse‐pored skin, minimal acne and oily scalp hair comprise a well‐known clinical entity. It causes considerable concern, has social impact, and affects the quality of life in some individuals. Some patients seek treatment for seborrhea. No effective topical sebosuppressive medication is available. Oral isotretinoin is the only remedy for men. In women, oral isotretinoin is the most effective remedy, followed by antiandrogens. Patients and methods: Eleven patients in three groups were treated for 6 months with very low dose isotretinoin. The influence on seborrhea was measured during oral treatment with 5 mg/d, 2.5 mg/d, or 2.5 mg 3× weekly. Results: Sebum production, measured with Sebutape®, was reduced by up to 64 %. Acne lesions regressed by as much as 84 %. Follicular filaments were reduced by 66 %. Microcomedones were reduced on average up to 86 %. Quantitative bacteriology showed a reduction of Propionibacterium acnes but no increase of Staphylococcus epidermidis. Biopsies revealed a 51 % reduction in sebaceous gland size. With Bentonite?, a reduction of lipids was demonstrated with 2.5 and 5 mg isotretinoin/d but not with 2.5 mg 3× weekly. There was a shift within the lipid fractions: triglycerides dominated, followed by squalenes and free fatty acids. Conclusions: Good results were achieved in all patients. The small number of patients did not permit a statistical analysis of the three isotretinoin doses studied, but there was a tendency toward better results with the two higher doses.     

Exercising caution: social physique anxiety and protective self-presentational behaviour

This study examined relations among body mass index (BMI), social physique anxiety (SPA) and protective self-presentational exercise behaviours in a sample of 86 female participants in aerobics classes at a university fitness centre. Participants completed a questionnaire assessing demographic and exercise-related information, the 9-item version of the Social Physique Anxiety Scale, and measures of two forms of protective self-presentational exercise behaviour (i.e., preferring to stand away from the aerobics instructor and wearing concealing exercise attire). Consistent with previous research, SPA was positively associated with both preferred exercise studio floor position (r = .31, p < .05) and clothing concealingness (r = .25, p < .05). SPA did not mediate the relations between BMI and either of the two protective self-presentational behaviours. BMI was a better predictor of clothing concealingness than SPA, but the opposite was found for exercise studio floor position preferences (r = .31 with SPA versus r = .15 with BMI). The findings provide an enhanced understanding of factors associated with self-presentation in exercise.     

Differential expression of Toll-like receptor 2 (TLR2) and responses to TLR2 ligands between human and murine vascular endothelial cells

Toll-like receptors (TLRs) initiate and maintain host defenses and inflammation, and directly contribute to diseases such as atherosclerosis. It is not completely understood in what cell types proatherogenic TLR-induced signaling arises and, particularly, there is uncertainty regarding the potential functional role of TLR2 in endothelial cells (ECs). We determined TLR2 and TLR4 gene expression in four different human and two different murine primary ECs using gene array analysis, RT-PCR, and flow cytometry and confirmed these data by functional studies by stimulating ECs with the corresponding TLR ligands. TLR4 was expressed in all human and murine ECs and these cells responded to stimulation with LPS. Faint expression of TLR2 was observed in human ECs, whereas murine ECs express considerable amounts of TLR2 mRNA. Human ECs failed to respond to TLR2 ligands while murine ECs responded to TLR2 ligands. Furthermore, in murine ECs, TLR2 was located on the cell surface while in human ECs, TLR2 was sequestered in intracellular compartments. After IFN-gamma or IL-1beta stimulation, TLR2 translocated to the cell surface of human ECs. In conclusion, TLR2 is expressed intracellularly in human ECs and, therefore, TLR2 ligands are inaccessible to the receptor. Murine ECs express membrane TLR2 and respond to TLR2 ligands, but human ECs normally will not respond unless they are first primed with inflammatory stimulation, which appears to trigger translocation of TLR2 to the cell surface.     

Activities of daptomycin and comparative antimicrobials, singly and in combination, against extracellular and intracellular Staphylococcus aureus and its stable small-colony variant in human monocyte-derived macrophages and in broth

We investigated the antistaphylococcal activities of daptomycin, gentamicin, and rifampin against two Staphylococcus aureus strains and their stable small-colony variants, singly and in combination, in human monocyte-derived macrophages and in broth. Intracellularly, the three-drug combination and two-drug combinations with rifampin were most effective. Extracellularly, daptomycin, daptomycin plus gentamicin, gentamicin plus rifampin, and the three-drug combination had similar activities.     

Treatment of vitiligo in children and adolescents by autologous cultured pure melanocytes transplantation with comparison of efficacy to results in adults

Background Transplantation of autologous cultured pure melanocytes is a well‐established procedure for the treatment of refractory and stabilized vitiligo. However, there was no report specifically comparing the efficacy with the regard to defined age groups (children‐adolescence‐adult). Objective We analysed the efficacy of this procedure in the treatment of vitiligo in children and adolescents and compare it with the results in adults treated during the same period and using identical procedures. Methods Melanocytes were isolated from the roof of suction blister, cultured and expanded with Hu16 medium in vitro, and transplanted to laser‐denuded receipt area. A total of 12 children (8–12 years), 20 adolescents (13–17 years) and 70 adults with vitiligo were treated using this procedure. Results The patients obtained satisfactory results (repigmentation of 50% or more) results in children, adolescents and adults were 83.3%, 95.0% and 84.0% respectively. The mean extent of repigmentation in children, adolescents and adults was 80.7%, 78.9% and 76.6% respectively. There was no statistical difference in repigmentation among these three groups. After adjusting for all factors (gender, type of vitiligo, period of stability, location of the lesion or transplanted cell density) individually or totally using multiple regression analysis, age still did not correlate to the extent of repigmentation. Conclusions The satisfactory results obtained in the treatment of vitiligo in children and adolescents by transplantation of cultured autologous pure melanocytes are comparable with the results in adults. Therefore, this procedure can be considered in refractory and stable vitiligo in children and adolescents, especially in patients with large vitiliginous lesions.