Toxicity of combined exposure to acrylamide and Staphylococcus aureus.

In the current study, the aim was to examine the toxicity of combined exposure to acrylamide and Staphylococcus aureus. We investigated the effect of staphylococcal enterotoxin A (SEA), a toxin produced by Staphylococcus aureus, on the oxidation induced DNA damaging potency of acrylamide in mouse spleen cells using an Formamidopyrimidine-DNA glycosylase-modified (FPG)-modified comet assay. Parameters like tail moment, tail length, and % tail DNA as indicators of DNA damage were significantly increased in the combined acrylamide and SEA treatment compared with SEA or acrylamide alone. Further, we examined the effects of acrylamide and its epoxide metabolite glycidamide on overall production of SEA, SEA mRNA gene expression, and on the formation of biofilm of S. aureus. Acrylamide significantly increased the SEA expression level and SEA production in S. aureus. Acrylamide also significantly increased biofilm formation in S. aureus without affecting its growth rate. Moreover, the addition of acrylamide significantly increased the expression of S. aureus virulence factors RNAIII and icaA in fetal bovine serum. Our results showed that combined exposure to acrylamide and S. aureus or its toxin enhanced their chemical and biological toxicities.

Mechanical Properties of Epoxy Compounds Based on Bisphenol a Aged in Aqueous Environments.

(1) Background: The aim of the work is to determine the influence of selected aqueous environments of various types of liquids on the strength of adhesive compositions prepared from epoxy resin based on bisphenol A combined with two different curing agents: tritethylenetetramine and polyaminoamide C. (2) Methods: The cured epoxy adhesive compounds samples were seasoned in four aqueous environments of the liquid: rainwater, demineralized water, tap water, and a sweetened drink. Three variants of the aging time in the above-mentioned operating environments were adopted: one month, two months, and three months. After the specified maturing time, samples of epoxy adhesive compositions were subjected to the strength tests on the Zwick/Roell 150 testing machine, which is in accordance with ISO 604 standard, determining the compressive strength. (3) Results: On the basis of the obtained strength test results and their analysis, it was noticed, inter alia, that the strength of the epoxy compounds decreases with the aging time in all used aqueous environments. Moreover, in the case of both types of the epoxy compounds, the highest strength was achieved after aging in demineralized water.

Cross-linking method using pentaepoxide for improving bovine and porcine bioprosthetic pericardia: A multiparametric assessment study.

Bioprosthetic heart valves made from bovine pericardium (BP) and porcine pericardium (PP) preserved with glutaraldehyde (GA) are commonly used in valve surgeries but prone to calcification in many patients. In this study, we compared BP and PP preserved with GA, ethylene glycol diglycidyl ether (DE), and 1,2,3,4,6-penta-O-{1-[2-(glycidyloxy)ethoxy]ethyl}-d-glucopyranose (PE). We studied the stabilities of DE and PE in preservation media along with the amino acid (AA) compositions, Fourier-transform infrared spectra, mechanical properties, surface morphologies, thermal stability, calcification, and the cytocompatibility of BP and PP treated with 0.625% GA, 5% DE, 2% PE, and alternating 5% DE and 2% PE for 3 + 11 d and 10 + 10 d, respectively. Both epoxides were stable in the water-buffer solutions (pH 7.4). DE provided high linkage densities in BP and PP owing to reactions with Hyl, Lys, His, Arg, Ser, and Tyr. PE reacted weakly with these AAs but strongly with Met. High cross-linking density obtained using the 10 d + 10 d method provided satisfactory thermal stability of biomaterials. The epoxy preservations improved cytocompatibility and resistance to calcification. PE enhanced the stress/strain properties of the xenogeneic pericardia, perhaps by forming nanostructures that were clearly visualised in BP using scanning electron microscopy. The DE + PE combination, in an alternating cross-linking manner, thus constitutes a promising option for developing bioprosthetic pericardia.

The Impact of the Acidic Environment on the Mechanical Properties of Epoxy Compounds in Different Conditions.

The aim of this work was to determine the impact of the acidic environment on the mechanical properties of two epoxy compounds in different conditions. The samples were made from the epoxy compounds composed of the epoxy resin (based on Bisphenol A), triethylenetetramine curing agent (unmodified compound), and calcium carbonate (CaCO3) (modified compound). The epoxy compound samples were seasoned for the following period of time (i.e., one week, one month, and three months). The environment was tap water and the acidic environment had three different concentrations of acetic acid (3%, 6%, and 9%). Strength tests of the epoxy compound samples were carried out in accordance with the ISO 604 standard. In the case of the modified composition, it is noted that the samples immersed in tap water were characterized by a higher strength than in acidic environments. A similar tendency was observed for unmodified compositions, although the differences were smaller than for the modified compositions. It was also noticed that the increase in the pH of the acidic solution in many analyzed cases contributed to the decrease in mechanical properties, although the immersion time in the acidic solution is important.

Experimental Study of Mechanical Properties of Epoxy Compounds Modified with Calcium Carbonate and Carbon after Hygrothermal Exposure.

The objective of this paper is to analyze the effects of hygrothermal exposure on the mechanical properties of epoxy compounds modified with calcium carbonate or carbon fillers. In addition, comparative tests were carried out with the same parameters as hygrothermal exposure, but the epoxy compounds were additionally exposed to thermal shocks. The analysis used cylindrical specimens produced from two different epoxy compounds. The specimens were fabricated from compounds of epoxy resins, based on Bisphenol A (one mixture modified, one unmodified) and a polyamide curing agent. Some of the epoxy compounds were modified with calcium carbonate (CaCO3). The remainder were modified with activated carbon (C). Each modifying agent, or filler, was added at a rate of 1 g, 2 g, or 3 g per 100 g of epoxy resin. The effect of the hygrothermal exposure (82 °C temperature and 95% RH humidity) was examined. The effects of thermal shocks, achieved by cycling between 82 °C and -40 °C, on selected mechanical properties of the filler-modified epoxy compounds were investigated. Strength tests were carried out on the cured epoxy compound specimens to determine the shear strength, compression modulus, and compressive strain. The analysis of the results led to the conclusion that the type of tested epoxy compounds and the quantity and type of filler determine the effects of climate chamber aging and thermal shock chamber processing on the compressive strength for the tested epoxy compounds. The different filler quantities, 1-3 g of calcium carbonate (CaCO3) or activated carbon (C), determined the strength parameters, with results varying from the reference compounds and the compounds exposure in the climate chamber and thermal shock chamber. The epoxy compounds which contained unmodified epoxy resin achieved a higher strength performance than the epoxy compounds made with modified epoxy resin. In most instances, the epoxy compounds modified with CaCO3 had a higher compressive strength than the epoxy compounds modified with C (activated carbon).

Construction workers' skin disorders in the Finnish Register of Occupational Diseases 2005-2016.

BACKGROUND: Construction workers are a known risk group for occupational skin disease (OSD). OBJECTIVES: To study diagnoses and causes of OSD in construction workers in the Finnish Register of Occupational Diseases (FROD) 2005-2016. MATERIALS AND METHODS: We searched the FROD for dermatological cases in (a) construction-related occupations defined by the International Standard Classification of Occupations (ISCO-08) and (b) in the industrial branch of construction defined by the Statistical Classification of Economic Activities in the European Community (NACE Rev. 2). RESULTS: The two searches yielded the same number of cases, 329, although they were not identical subgroups. The number of allergic contact dermatitis (ACD) cases was 235 (71%) in construction-related occupations and 228 (69%) in the industrial branch of construction. In the latter analysis, synthetic resin systems caused 66% of ACD cases and 46% of all OSDs, epoxy compounds being the leading cause (122 cases; 54% of ACD cases; 37% of all OSDs). Metals were the second most common group of causes of ACD with 31 cases (chrome 22 cases; cobalt 8 cases). Isothiazolinones caused ACD in 21 cases, many of whom were painters. CONCLUSIONS: ACD dominated the OSDs of construction workers and epoxy products were by far the leading cause comprising 37% of all OSDs. Chrome and isothiazolinones were also prominent causes of ACD.

Population pharmacokinetic approach for evaluation of treosulfan and its active monoepoxide disposition in plasma and brain on the basis of a rat model.

PURPOSE: Efficacy of treosulfan, used in the treatment of marrow disorders, depends on the activity of its monoepoxy-(EBDM) and diepoxy compounds. The study aimed to describe the pharmacokinetics of treosulfan and EBDM in the rat plasma and brain by means of mixed-effects modelling. METHODS: The study had a one-animal-per-sample design and included ninty-six 10-week-old Wistar rats of both sexes. Treosulfan and EBDM concentrations in the brain and plasma were measured by an HPLC-MS/MS method. The population pharmacokinetic model was established in NONMEM software with a first-order estimation method with interaction. RESULTS: One-compartment pharmacokinetic model best described changes in the concentrations of treosulfan in plasma, and EBDM concentrations in plasma and in the brain. Treosulfan concentrations in the brain followed a two-compartment model. Both treosulfan and EBDM poorly penetrated the blood-brain barrier (ratio of influx and efflux clearances through the blood-brain barrier was 0.120 and 0.317 for treosulfan and EBDM, respectively). Treosulfan plasma clearance was significantly lower in male rats than in females (0.273 L/h/kg vs 0.419 L/h/kg). CONCLUSIONS: The developed population pharmacokinetic model is the first that allows the prediction of treosulfan and EBDM concentrations in rat plasma and brain. These results provide directions for future studies on treosulfan regarding the contribution of transport proteins or the development of a physiological-based model.

Relationship between exposure to treosulfan and its monoepoxytransformer - An insight from population pharmacokinetic study in pediatric patients before hematopoietic stem cell transplantation.

Treosulfan (TREO), a structural analog of busulfan, is currently studied as a myeloablative agent in conditioning regimens before hematopoietic stem cell transplantation in pediatric patients. High exposure to TREO (>1650 mg∗h/mL) might be related to early toxicity, especially skin toxicity and mucositis. The aim of the present study was to investigate a potential relationship between exposure to TREO and its monoepoxytransformer (S,S-EBDM), as well as variability of the pharmacokinetics of these entities by means of a population pharmacokinetic approach with a non-linear mixed-effects analysis. The study included data from 14 children with malignant and non-malignant diseases treated with TREO in daily doses 10-14 g/m2. The parent-metabolite population pharmacokinetic model was developed in NONMEM 7.3 software. Upon the constructed model, an extensive simulation was performed to assess the correlation between exposure to TREO and S,S-EBDM. It was found that TREO and S,S-EBDM pharmacokinetics was best described with 2-compartmental and 1-compartmental linear models, respectively. The vast majority (>65%) of TREO was transformed to S,S-EBDM. Overall, a considerable interpatient variability of pharmacokinetic parameters was observed, especially the clearance of S,S-EBDM. A weak correlation was found between the exposure to TREO and S,S-EBDM (r = 0.1681, p < 0.0001). Also, patients with an exposure to TREO above 1650 mg∗h/mL were most likely to have also a high exposure to S,S-EBDM (35.38 µM∗h vs. 43.14 µM∗h, p < 0.0001). In summary, a parent-metabolite population pharmacokinetic model for TREO and S,S-EBDM was developed for the first time. It was shown that there is a weak correlation between exposure to TREO and S,S-EBDM. Therefore therapeutic drug monitoring of not only prodrug but also its active epoxide might be needed.

Effects of interleukin-34 on prostaglandin E2 expression of fibroblast-like synoviocytes in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective To investigate the effects of interleukin-34 (IL-34) on prostaglandin E2 (PGE2)/cyclo-oxygenase-2 (COX-2) expression on fibroblast-like synoviocytes (FLS) in patients with rheumatoid arthritis (RA). Methods FLS was isolated from 6 RA patients and stimulated with IL-34 (50 ng/ml), IL-34 receptor antagonist (25 ng/ml) and IL-34 (50 ng/ml), inhibitors of signaling pathway (10 μmol/L) and IL-34 (50 ng/ml) in vitro respectively. The expression of COX-2 mRNA was detected by reverse transcription polymerase chain reac-tion (RT-PCR). The level of PGE2 in the supernatant of RA FLS culture was measured by Enzyme linked immunosorbent assay (ELISA). Statistical analysis between groups were performed by t test. Results Com-pared to unstimulated FLS, COX-2 and PGE2 expression was increased dramatically on IL-34-stimulated FLS, most evidently in 48 hours [(139±24) pg/ml vs (201±8) pg/ml, t=-6.177, P<0.01]; Moreover, the level of PGE2 was decreased when anti-IL-34 antibody was added to the IL-34-stimulated RA FLS at 24 hours, 48 hours, 72 hours [(250 ±58) pg/ml vs (100 ±28) pg/ml, t=5.742, P<0.01; (375 ±24) pg/ml vs (97 ±23) pg/ml, t=20.564, P<0.001; (357 ±21) pg/ml vs (94 ±18) pg/ml, t=22.353, P<0.01]; In the presence of SB203580 and IKK-16, PGE2 level produced by IL-34-stimulated FLS was obviously decreased [(279 ±37) pg/ml vs (63 ±17) pg/ml, t=12.806, P<0.01;(279±37) pg/ml vs (77±16) pg/ml, t=6.177, P<0.01]. Conclusion Binding of IL-34 with its receptor may promote the secretion of PGE2 via NF-κB and P38 MAPK signaling pathway in RA FLS, suggesting that it might be involved in the pathogenesis of RA.

Cytotoxicity analysis of electrostatically applied epoxy coating onto CO-CR alloy / Análise da citotoxidade de pintura epóxi na aplicação eletrostática sobre liga de CO-CR

Objective: To investigate the biological effect of a new method to camouflage the cobalt-chromium (CoCr) metal structure of an RPD, onto which an electrostatic paint was applied.Methods: In vitro cytotoxicity of epoxy Politherm NOBAC30C (Weg Industries SA, Santa Catarina, Brazil) in combination with polished CoCr was tested by placing it in contact with cultured human fibroblasts and comparing it with polystyrene (control surface). The cells were cultured in the presence of the test surfaces for 24, 48, 72, 94 and 120 hours. The number of viable and non-viable cells was established by manual counting. The Tukey test was used to statistically analyze cell counts between the groups.Results: The results showed that cell proliferation was similar between the groups (p =0.2174). It was observed that at 24, 48 and 72 h, there was no significant increase in cell proliferation in all groups. From 96 to 120 h, an increase in cell proliferation was observed in all groups, with no significant difference between them (p>0.05).Conclusion: The epoxy paint studied showed no cytotoxicity in vitro.

Objetivos: Analisar, biologicamente, a possibilidade do uso de pintura por aplicação eletrostática.Métodos: Por meio de testes in vitro de citotoxicidade, comparando o comportamento da tinta epóxi Politherm 30 Nobac C (Weg Indústrias S.A, Santa Catarina, Brasil) com CoCr polido e poliestireno em contato com cultura de fibroblastos humanos. Esse teste foi realizado através de contagem de células viáveis e não viáveis em tempos de 24, 48, 72, 94 e 120 horas. Para a contagem de células viáveis foi aplicada a Análise Estatística de Tukey.Resultados: Os resultados obtidos na presente pesquisa mostraram que o comportamento de crescimento celular foi estatisticamente semelhante entre grupos (p=0,2174). Observou-se que nos tempos de 24, 48 e 72 horas, não houve aumento estatisticamente significante da proliferação celular, mantendo-se o padrão para todos os grupos estudados. A partir de 96 e 120 h observamos um aumento da proliferação celular para todos os grupos estudados, sem diferenças entre os mesmos também (p>0,05). Para os resultados de células inviáveis, aplicou-se a Análise não Paramétrica de Kruskal Wallis e o teste de Dunn, devido à baixa taxa de morte celular, sem diferença estatisticamente entre os grupos (p>0,05).Conclusão: Conclui-se, portanto, que a pintura Epóxi estudada não apresentou citotoxicidade para os testes realizados in vitro.

Influence of ATRA on in-vitro proliferation of human lung adenocarcinoma cell line A 549 and its mechanisms / 重庆医学

Objective To explore the influence of all-trans retinoic acid(ATRA) on in-vitro proliferation of human lung adeno-carcinoma cell line A549 and to preliminarily study its mechanism .Methods The human lung adenocarcinoma cell line A549 was taken as the experimental group .The cells in the experimental group and the control group were detected by using 3-(4 ,5-dimethyl-thiazol-2-yl)-2 ,5-diphenyltetrazolium bromide(MTT) assay for calculating the cell growth inhibition rate ;the microstructure of the cultured cells was observed by the transmission electron microscope technique ;the expression of cyclooxygenase-2(COX-2) in the cell supernate was detected by the enzyme linked immunosorbent assay .Results The different concentrations of ATRA for treating A549 cells could produce the inhibiting effect on A 549 cells to some different degrees ,furthermore ,after 72 h ,the expression of COX-2 in cytoplasma among the various concentrations groups was significantly decreased ,which was positively correlated with the concentration ,the difference showing statistical significance (P< 0 .05);at the same time ,by detecting TRAIL expression level in the experimental group(1 × 10-5 mol/L ,1 × 10-4 mol/) ,the expression of TRAIL in the A549 cell supernate after ATRA treatment was increased .Conclusion ATRA has the significant anti-tumor effect on the lung adenocarcinoma cell line A549 with the concen-tration-time dependence;ATRA in lung cancer tissue may play its anti-tumor effect by inducing apoptosis ,which can provide the theoretical basis for the treatment of lung cancer .

Expression and biological significance of mPGES-1 and COX-2 in lung cancer / 中国基层医药

ObjectiveTo explore the expression and biological significance of microsomal prostaglan din E synthase-1 ( mPGES-1 ) and cyclooxyenase-2 (COX-2) in lung cancer.MethodsThe expressions of mPGES-1 and COX-2 mRNA in cancerous tissue and tumor-adjacent tissue were detected by RT-PCR,while the immunohistochemical S-P method was used to evaluate the expression of mPGES-1 and COX-2 proteins in the corresponding tissues.ResultsThe mRNA level of COX-2 and mPGES-1 significantly increased( P ＜0.05) in lung cancer group as compared with those in the tumor-adjacent tissue.The positive expression rate of mPGES-1 in cancerous tissue and tumoradjacent tissue were 66.7％ (40/60) and 10.0％ (6/60) respectively.The positive expression rate of COX-2 protein in cancerous tissue and tumor-adjacent tissue were 73.3％ (44/60)and 13.3％ (8/60),respectively.The positive expression rate of COX-2 was significantly higher in lung cancer than m tumor-adjacent tissue( x =21.99,P ＜ 0.01 ).The positive expression rate of mPGES-1 and COX-2 protein in lung cancer was independent of size of tumor and histological type(P ＞0.05 ),but correlated with histological grade,lymph node metastasis and TNM staging.(P ＜0.05 ).ConclusionIt suggested that the expression of mPGES-1 and COX-2 in lung cancer may play an important role in the process of carcinogenesis,and may provide a clinical basis for the early diagnosis and targeted therapy of lung cancer.

The expression of NF-κB and COX-2 protein in renal cell carcinoma and its clinical value / 肿瘤研究与临床

Objective To study the expression of NF-κB and COX-2 protein in renal cell carcinoma, and to investigate the clinical value of it in the occurrence, progression and metastasis of renal cell carcinoma as well as the prognosis of patients. Methods 48 cases of renal cell carcinoma tissues and 5 cases of normal renal tissues were detected by using immunohistochemical method, and following up the patients who were included in the study. Then we analyzed the relationship between NF-κB and COX-2 protein level and clinic pathological parameters as well as the prognosis of patients. Resalts The expression of NF-κB and COX-2 protein were increasing in renal cell carcinoma, the protein levels were significantly different compared with that in normal renal tissues(P <0.05). There were significantly positive correlation between the expression of NF-κB protein and the clinic stages of renal cell earcinoma(P <0.05), but no correlation between the expression of COX-2 protein and them(P >0.05). There were significantly negative correlation between the expression of COX-2 protein and the pathological grades of renal cell careinoma(P <0.05), but no correlation between the expression of NF-κB protein and them (P>O.05). The survival rate of these patients whose expression of NF-κB protein were positive was significantly lower than those of negative expression of NF-κB protein(P <0.05), and there was opposite result for COX-2, but not significanfly(P >0.05). The expression of NF-κB and COX-2 protein in renal cell carcinoma had no significant correlation (P >0.05). Conclusion There may be relationship between the expression of NF-κB and COX-2 protein and the occurrence, progression of renal cell carcinoma, the expression of NF-κB may also have association with metastasis of renal cell carcinoma as well as the prognosis of patients. Detecting the expression of NF-κB and COX-2 protein may be useful in early diagnosis of renal cell carcinoma as well as prognosis evaluation of patients.

Expression and their clinical significance of COX-2 and MMP-7 in laryngeal squamous cell carcinoma / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the expression of cycloxygenase-2(COX-2)and matrix metalloproteinase-7(MMP-7)in laryngeal squamous cell carcinoma(LSCC)and their clinical significance. METHODS The expression of COX-2 and MMP-7 in 65 LSCC tissues and 34 adjacent non-neoplastic tissues were studied by immunohistochemical SP method. RESULTS The expression of COX-2 and MMP-7 was observed in 72.3% and 75.4% of the LSCC tissues and in 20.6% and 23.5% of the adjacent non- neoplastic tissues respectively,which had a significant difference(P

Expression of COX-2 and the relationship between COX-2 and PTEN in endometrial adenocarcinoma / 肿瘤研究与临床

Objective To study the expression and clinical significance of COX-2 and the relation- ship between COX-2 and PTEN in endometrial adenocarcinoma(EAC).Methods The expression of COX-2, PTEN protein was detected by SP-immunohistochemical method in EAC,endometrial intraepithelial neoplasia, corresponding normal endometrium.Results The positive rates of COX-2 protein increased from normal en- dometrium(13.33%) to endometrial intraepithelial neoplasia(50.00%) and adenocarcinoma(64.58 %)(P

Detoxication strategy of epoxide hydrolase-the basis for a novel threshold for definable genotoxic carcinogens.

From our recent work on the three-dimensional structure of epoxide hydrolases we theoretically deduced the likelihood of a two-step catalytic mechanism that we and others have subsequently experimentally confirmed. Analysis of the rate of the two steps by us and by others show that the first step-responsible for removal of the reactive epoxide from the system-works extraordinarily fast (typically three orders of magnitude faster than the second step), sucking up the epoxide like a sponge. Regeneration of the free enzyme (the second step of the catalytic mechanism) is slow. This becomes a toxicological problem only at doses of the epoxide that titrate the enzyme out. Our genotoxicity work shows that indeed this generates a practical threshold below which no genotoxicity is observed. This shows that-contrary to old dogma-practical thresholds exist for definable genotoxic carcinogens.

Significance of the expression of cyclooxygenase-2 in breast cancers / 肿瘤研究与临床

Objective To investigate the expression of cyclooxygenase-2(COX-2)in breast cancers, and understand its clinical significance.Methods The immunohistochemistry was used to determine the ex- pression of COX-2 in the 40 tissues of breast cancer and 18 adjacent noncancerous mammary tissues.Results The positive expression of COX-2 was detected in 52.5% of breast cancer tissues and in 11.1% of adjacent noncancerous mammary tissues.There was a significant difference in the expression of COX-2 between breast cancer tissues and adjacent noncancerous mammary tissues(P0.05).Conclusion COX-2 was over expressed in breast cancer and correlated with metastatic lymph nodes and HER-2/neu.The expression of COX-2 may play an important role in carcinogen- esis,progression and prognosis of breast cancer.

Epoxyeicosatrienoic acid: The signal transduction / 中国病理生理杂志

Cytochrome P450 monoxygenase converts arachionic acid to four epoxyeicosatrienoic acid regiosomes: 5,6-EET(epoxyeicosatrienoic acid);8,9-EET; 11,12-EET and 14,15-EET.Recent studies show that EETs are involved in signal transduction. EETs open Ca 2+ -sensitive K + channel and inhibit Na + channel,Ca 2+ -sensitive Cl - channel and so on. What is more ,EETs have been demonstrated to activate PP60 c-src and initiate a tyrosine kinase cascade that mediates mitogenic effects.