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Biosensors Feb 2021Chlorophene is an important antimicrobial agent present in disinfectant products which has been related to health and environmental effects, and its detection has been...
Chlorophene is an important antimicrobial agent present in disinfectant products which has been related to health and environmental effects, and its detection has been limited to chromatographic techniques. Thus, there is a lack of research that attempts to develop new analytical tools, such as biosensors, that address the detection of this emerging pollutant. Therefore, a new biosensor for the direct detection of chlorophene in real water is presented, based on surface plasmon resonance (SPR) and using a laccase enzyme as a recognition element. The biosensor chip was obtained by covalent immobilization of the laccase on a gold-coated surface through carbodiimide esters. The analytical parameters accomplished resulted in a limit of detection and quantification of 0.33 mg/L and 1.10 mg/L, respectively, fulfilling the concentrations that have already been detected in environmental samples. During the natural river's measurements, no significant matrix effects were observed, obtaining a recovery percentage of 109.21% ± 7.08, which suggested that the method was suitable for the fast and straightforward analysis of this contaminant. Finally, the SPR measurements were validated with an HPLC method, which demonstrated no significant difference in terms of precision and accuracy, leading to the conclusion that the biosensor reflects its potential as an alternative analytical tool for the monitoring of chlorophene in aquatic environments.
Topics: Anti-Infective Agents; Biosensing Techniques; Carbodiimides; Dichlorophen; Gold; Limit of Detection; Surface Plasmon Resonance
PubMed: 33572259
DOI: 10.3390/bios11020043 -
Environmental Health Perspectives Oct 2020Endocrine-disrupting chemicals can interfere with hormonal homeostasis and have adverse effects for both humans and the environment. Their identification is increasingly...
BACKGROUND
Endocrine-disrupting chemicals can interfere with hormonal homeostasis and have adverse effects for both humans and the environment. Their identification is increasingly difficult due to lack of adequate toxicological tests. This difficulty is particularly problematic for cosmetic ingredients, because testing is now banned completely in the European Union.
OBJECTIVES
The aim was to identify candidate preservatives as endocrine disruptors by methods and to confirm endocrine receptors' activities through nuclear receptors .
METHODS
We screened preservatives listed in Annex V in the European Union Regulation on cosmetic products to predict their binding to nuclear receptors using the Endocrine Disruptome and VirtualToxLab™ version 5.8 tools. Five candidate preservatives were further evaluated for androgen receptor (AR), estrogen receptor (), glucocorticoid receptor (GR), and thyroid receptor (TR) agonist and antagonist activities in cell-based luciferase reporter assays in AR-EcoScreen, , MDA-kb2, and GH3.TRE-Luc cell lines. Additionally, assays to test for false positives were used (nonspecific luciferase gene induction and luciferase inhibition).
RESULTS
Triclocarban had agonist activity on AR and at and antagonist activity on GR at and TR at . Triclosan showed antagonist effects on AR, , GR at and TR at , and bromochlorophene at (AR and TR) and at ( and GR). AR antagonist activity of chlorophene was observed [inhibitory concentration at 50% (IC) ], as for its substantial agonist at and TR antagonist activity at . Climbazole showed AR antagonist (), agonist at , and TR antagonist activity at .
DISCUSSION
These data support the concerns of regulatory authorities about the endocrine-disrupting potential of preservatives. These data also define the need to further determine their effects on the endocrine system and the need to reassess the risks they pose to human health and the environment. https://doi.org/10.1289/EHP6596.
Topics: Androgen Receptor Antagonists; Carbanilides; Cell Line; Computer Simulation; Dichlorophen; Endocrine Disruptors; Genes, Reporter; Humans; Imidazoles; Receptors, Androgen; Receptors, Estrogen; Receptors, Glucocorticoid; Triclosan
PubMed: 33064576
DOI: 10.1289/EHP6596 -
ACS Omega Sep 2020The rising prevalence of multidrug-resistant hospital-acquired infections has increased the need for new antibacterial agents. In this study, a library of 1586...
The rising prevalence of multidrug-resistant hospital-acquired infections has increased the need for new antibacterial agents. In this study, a library of 1586 FDA-approved drugs was screened against , a representative of the complex. Three compounds were found to have previously undiscovered antibacterial properties against : antifungal Miconazole, anthelminthic Dichlorophen, and Bithionol. These three drugs were tested against a wide range of Gram-positive and Gram-negative bacteria and confirmed to have broad-spectrum antibacterial properties. Combinations of these three drugs were also tested against the same bacteria, and two novel combination therapies with synergistic effects were discovered. In the future, antibacterial properties of these three drugs and two combination therapies will be evaluated against pathogenic bacteria using an animal model.
PubMed: 32984715
DOI: 10.1021/acsomega.0c03211 -
ACS Omega Sep 2020Of the numerous infectious diseases afflicting humans, anthrax disease, caused by , poses a major threat in its virulence and lack of effective treatment. The currently...
Of the numerous infectious diseases afflicting humans, anthrax disease, caused by , poses a major threat in its virulence and lack of effective treatment. The currently lacking standards of care, as well as the lengthy drug approval process, demonstrate the pressing demand for treatment for infections. The present study screened 1586 clinically approved drugs in an attempt to identify repurposable compounds against , a relative strain that shares many physical and genetic characteristics with . Our study yielded five drugs that successfully inhibited growth: dichlorophen, oxiconazole, suloctidil, bithionol, and hexestrol. These drugs exhibited varying levels of efficacy in broad-spectrum experiments against several Gram-positive and Gram-negative bacterial strains, with hexestrol showing the greatest inhibition across all tested strains. Through tests for the efficacy of each drug on , bithionol was the single most potent compound on both solid and liquid media and exhibited even greater eradication of in combination with suloctidil on solid agar. This multifaceted study of approved drugs demonstrates the potential to repurpose these drugs as treatments for anthrax disease in a time-efficient manner to address a global health need.
PubMed: 32905429
DOI: 10.1021/acsomega.0c03207 -
Brazilian Journal of Microbiology :... Dec 2020With the high-frequency use or abuse of antifungal drugs, the crisis of drug-resistant fungi continues to increase worldwide; in particular, the infection of...
With the high-frequency use or abuse of antifungal drugs, the crisis of drug-resistant fungi continues to increase worldwide; in particular, the infection of drug-resistant Candida albicans brings the great challenge to the clinical treatment. Therefore, to decelerate the spread of this resistance, it is extremely urgent to facilitate the new antifungal targets with novel drugs. Phosphopantetheinyl transferases PPTases (Ppt2 in Candida albicans) had been identified in bacterium and fungi and mammals, effects as a vital enzyme in the metabolism of organisms in C. albicans. Ppt2 transfers the phosphopantetheinyl group of coenzyme A to the acyl carrier protein Acp1 in mitochondria for the synthesis of lipoic acid that is essential for fungal respiration, so making Ppt2 an ideal target for antifungal drugs. In this study, 110 FDA-approved drugs were utilized to investigate the Ppt2 inhibition against drug-resistant Candida albicans by the improved fluorescence polarization experiments, which have enough druggability and structural variety under the novel strategy of drug repurposing. Thereinto, eight agents revealed the favourable Ppt2 inhibitory activities. Further, broth microdilution assay of incubating C. albicans with these eight drugs showed that pterostilbene, procyanidine, dichlorophen and tea polyphenol had the superior MIC values. In summary, these findings provide more valuable insight into the treatment of drug-resistant C. albicans.
Topics: Antifungal Agents; Candida albicans; Drug Repositioning; Drug Resistance, Fungal; Enzyme Inhibitors; Fungal Proteins; Microbial Sensitivity Tests; Transferases (Other Substituted Phosphate Groups)
PubMed: 32557281
DOI: 10.1007/s42770-020-00318-w -
The Journal of Biological Chemistry May 2020-Acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) (EC 3.1.4.4) catalyzes the final step in the biosynthesis of -acyl-ethanolamides. Reduced NAPE-PLD expression...
-Acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) (EC 3.1.4.4) catalyzes the final step in the biosynthesis of -acyl-ethanolamides. Reduced NAPE-PLD expression and activity may contribute to obesity and inflammation, but a lack of effective NAPE-PLD inhibitors has been a major obstacle to elucidating the role of NAPE-PLD and -acyl-ethanolamide biosynthesis in these processes. The endogenous bile acid lithocholic acid (LCA) inhibits NAPE-PLD activity (with an IC of 68 μm), but LCA is also a highly potent ligand for TGR5 (EC 0.52 μm). Recently, the first selective small-molecule inhibitor of NAPE-PLD, ARN19874, has been reported (having an IC of 34 μm). To identify more potent inhibitors of NAPE-PLD, here we used a quenched fluorescent NAPE analog, PED-A1, as a substrate for recombinant mouse Nape-pld to screen a panel of bile acids and a library of experimental compounds (the Spectrum Collection). Muricholic acids and several other bile acids inhibited Nape-pld with potency similar to that of LCA. We identified 14 potent Nape-pld inhibitors in the Spectrum Collection, with the two most potent (IC = ∼2 μm) being symmetrically substituted dichlorophenes, hexachlorophene and bithionol. Structure-activity relationship assays using additional substituted dichlorophenes identified key moieties needed for Nape-pld inhibition. Both hexachlorophene and bithionol exhibited significant selectivity for Nape-pld compared with nontarget lipase activities such as PLD or serum lipase. Both also effectively inhibited NAPE-PLD activity in cultured HEK293 cells. We conclude that symmetrically substituted dichlorophenes potently inhibit NAPE-PLD in cultured cells and have significant selectivity for NAPE-PLD other tissue-associated lipases.
Topics: Animals; Bacterial Proteins; Bithionol; Dichlorophen; Enzyme Inhibitors; HEK293 Cells; Hexachlorophene; Humans; Mice; Phospholipase D; Quinazolines; Streptomyces; Sulfonamides
PubMed: 32284327
DOI: 10.1074/jbc.RA120.013362 -
British Journal of Pharmacology Apr 2016High-throughput screening of compound libraries using genetically encoded fluorescent biosensors has identified several second-generation. low MW inhibitors of the...
BACKGROUND AND PURPOSE
High-throughput screening of compound libraries using genetically encoded fluorescent biosensors has identified several second-generation. low MW inhibitors of the calcium-activated chloride channel anoctamin 1 (CaCC/Ano1). Here we have (i) examined the effects of these Ano1 inhibitors on gastric and intestinal pacemaker activity; (ii) compared the effects of these inhibitors with those of the more classical CaCC inhibitor, 5-nitro-2-(3-phenylpropylalanine) benzoate (NPPB); (ii) examined the mode of action of these compounds on the waveform of pacemaker activity; and (iii) compared differences in the sensitivity between gastric and intestinal pacemaker activity to the Ano1 inhibitors.
EXPERIMENTAL APPROACH
Using intracellular microelectrode recordings of gastric and intestinal muscle preparations from C57BL/6 mice, the dose-dependent effects of Ano1 inhibitors were examined on spontaneous electrical slow waves.
KEY RESULTS
The efficacy of second-generation Ano1 inhibitors on gastric and intestinal pacemaker activity differed significantly. Antral slow waves were more sensitive to these inhibitors than intestinal slow waves. CaCCinh -A01 and benzbromarone were the most potent at inhibiting slow waves in both muscle preparations and more potent than NPPB. Dichlorophene and hexachlorophene were equally potent at inhibiting slow waves. Surprisingly, slow waves were relatively insensitive to T16Ainh -A01 in both preparations.
CONCLUSIONS AND IMPLICATIONS
We have identified several second-generation Ano1 inhibitors, blocking gastric and intestinal pacemaker activity. Different sensitivities to Ano1 inhibitors between stomach and intestine suggest the possibility of different splice variants in these two organs or the involvement of other conductances in the generation and propagation of pacemaker activity in these tissues.
Topics: Animals; Anoctamin-1; Benzbromarone; Chloride Channels; Dichlorophen; Dose-Response Relationship, Drug; Gastrointestinal Tract; Hexachlorophene; High-Throughput Screening Assays; Mice; Mice, Inbred C57BL; Structure-Activity Relationship; Thiophenes
PubMed: 26774021
DOI: 10.1111/bph.13431 -
BMC Oral Health May 2011The aim of this study was to compare the reaction of rat connective tissue to two root-end filling materials: white Mineral Trioxide Aggregate (WMTA) and Diaket. (Comparative Study)
Comparative Study
BACKGROUND
The aim of this study was to compare the reaction of rat connective tissue to two root-end filling materials: white Mineral Trioxide Aggregate (WMTA) and Diaket.
METHODS
Each of the materials was placed in dentine tubes and implanted subcutaneously in the dorsal connective tissue of 21 Wistar albino rats. Tissue biopsies were collected 7, 30, and 60 days after the implantation procedure. The specimens were processed and stained with hematoxylin and eosin and examined microscopically. After determining inflammatory cell numbers in sections from each specimen, inflammatory reaction scores were defined as follows: 0; no or few inflammatory cells (no reaction), 1; less than 25 cells (mild reaction), 2; 25 to 125 cells, (moderate reaction), and 3; 125 or more cells (severe reaction). Statistical analysis was performed using the Kruskal-Wallis and Mann-Whitney tests.
RESULTS
There were statistically significant differences in the median inflammatory cell numbers throughout the three test periods, with the most severe degree of inflammation observed at the one-week period. Few cases of necrosis were observed with WMTA. Diaket exhibited the most severe degree of inflammation and necrosis. After 30 days, both materials provoked moderate inflammatory reaction. The eight-week period showed the least severe degree of inflammation in all groups.
CONCLUSIONS
It was concluded that WMTA exhibits a more favourable tissue response compared with Diaket which induced more severe inflammatory reaction than WMTA and the control.
Topics: Aluminum Compounds; Animals; Bismuth; Calcium Compounds; Connective Tissue; Dentin; Drug Combinations; Humans; Inflammation; Male; Oxides; Polyvinyls; Rats; Rats, Wistar; Root Canal Filling Materials; Silicates; Statistics, Nonparametric; Time Factors; Zinc Oxide
PubMed: 21569463
DOI: 10.1186/1472-6831-11-17 -
Journal of Applied Oral Science :... 2010This paper reports the nonsurgical endodontic therapy using calcium hydroxide intracanal dressing and prosthetic treatment of 9 teeth with periapical lesions in a...
This paper reports the nonsurgical endodontic therapy using calcium hydroxide intracanal dressing and prosthetic treatment of 9 teeth with periapical lesions in a 16-year-old female patient. The periodontal treatment plan included oral hygiene instructions, mechanical debridement and gingivectomy in the maxillary incisors to improve gingival contouring. Root canal treatment was indicated for teeth 11-13, 21, 22, 42-45. After successive changes of a calcium hydroxide intracanal dressing during 6 weeks, the size of the periapical radiolucencies decreased and lesion remission occurred after root canal obturation. The endodontically treated teeth received a bondable polyethylene reinforcement fiber (Ribbond) in the prepared canal space and crown buildup was done with composite resin. Prosthetic rehabilitation was planned with single-unit metal-ceramic crowns and fixed partial dentures. Clinical and radiographic evaluation after 6 months showed successful results. The outcomes of this case showed that chronic periapical lesions can respond favorably to nonsurgical endodontic treatment in adolescent patients and that, with proper indication, polyethylene fibers can provide an effective conservative and esthetic option for reinforcing endodontically treated teeth undergoing prosthetic rehabilitation.
Topics: Adolescent; Bismuth; Crowns; Dental Pulp Necrosis; Denture, Partial, Fixed; Drug Combinations; Female; Gingivectomy; Gutta-Percha; Humans; Periapical Periodontitis; Polyethylenes; Polyvinyls; Post and Core Technique; Root Canal Filling Materials; Root Canal Irrigants; Root Canal Obturation; Root Canal Therapy; Sodium Hypochlorite; Tooth Extraction; Zinc Oxide
PubMed: 20485933
DOI: 10.1590/s1678-77572010000200016 -
Journal of Applied Oral Science :... 2009During mechanical preparation of the post space, the root canal filling may be twisted or vibrated, depending on several factors associated with the preparation... (Comparative Study)
Comparative Study Randomized Controlled Trial
UNLABELLED
During mechanical preparation of the post space, the root canal filling may be twisted or vibrated, depending on several factors associated with the preparation technique and quality of filling.
OBJECTIVE
The purpose of this study was to investigate the effect of immediate and delayed post space preparation on the integrity of the apical seal.
MATERIAL AND METHODS
Sixty-four extracted human incisors were biomechanically prepared using the step-back technique. Sixty roots were randomly assigned to 6 experimental groups of 10 teeth each and the remaining 4 roots served as positive and negative controls (n=2). The root canals in the different groups were obturated with cold lateral and warm vertical condensation of gutta-percha and one of two sealers (Sealapex and Diaket). Post space was prepared either individually or simultaneously. An insulated copper wire was cut into 10-cm-long pieces. In each canal, one piece was inserted to maintain contact with gutta-percha and extended to the outside as one of two working electrodes. A stainless steel wire with the same dimensions of those of the copper wire, used as the other working electrode, was immersed into the background electrolyte from the center of the bottle. The electrical current between standard and experimental electrodes in canals was measured over a period of 10 days applying a conductivity meter. The Kruskal-Wallis test (p=0.05) determined whether there was a significant difference in microleakage among the groups and the Mann-Whitney U test (p=0.01) was used for multiple comparison grouping variables.
RESULTS
The results suggest that only the differences between the root canal filling techniques were statistically significant (p<0.01). There were no statistically significant difference in the sealers and the times of filling removal for post space preparation (p>0.01).
CONCLUSION
The quality of the root canal filling is important for the integrity of the apical seal.
Topics: Bismuth; Calcium Hydroxide; Conductometry; Dental Bonding; Dental Leakage; Dental Pulp Cavity; Drug Combinations; Electrodes; Gutta-Percha; Humans; Incisor; Materials Testing; Polyvinyls; Post and Core Technique; Root Canal Filling Materials; Root Canal Obturation; Root Canal Preparation; Salicylates; Time Factors; Zinc Oxide
PubMed: 20027435
DOI: 10.1590/s1678-77572009000600013