10-DEBC Hydrochloride as a Promising New Agent against Infection of Mycobacterium abscessus

Mycobacterium abscessus (M. abscessus) causes chronic pulmonary infections. Its resistance to current antimicrobial drugs makes it the most difficult non-tuberculous mycobacteria (NTM) to treat with a treatment success rate of 45.6%. Therefore, there is a need for new therapeutic agents against M. abscessus. We identified 10-DEBC hydrochloride (10-DEBC), a selective AKT inhibitor that exhibits inhibitory activity against M. abscessus. To evaluate the potential of 10-DEBC as a treatment for lung disease caused by M. abscessus, we measured its effectiveness in vitro. We established the intracellular activity of 10-DEBC against M. abscessus in human macrophages and human embryonic cell-derived macrophages (iMACs). 10-DEBC significantly inhibited the growth of wild-type M. abscessus and clinical isolates and clarithromycin (CLR)-resistant M. abscessus strains. 10-DEBC’s drug efficacy did not have cytotoxicity in the infected macrophages. In addition, 10-DEBC operates under anaerobic conditions without replication as well as in the presence of biofilms. The alternative caseum binding assay is a unique tool for evaluating drug efficacy against slow and nonreplicating bacilli in their native caseum media. In the surrogate caseum, the mean undiluted fraction unbound (fu) for 10-DEBC is 5.696. The results of an in vitro study on the activity of M. abscessus suggest that 10-DEBC is a potential new drug for treating M. abscessus infections.

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Clomiphene Citrate Shows Effective and Sustained Antimicrobial Activity against Mycobacterium abscessus

International Journal of Molecular Sciences ◽

10.3390/ijms222011029 ◽

2021 ◽

Vol 22 (20) ◽

pp. 11029

Author(s):

Da-Gyum Lee ◽

Yoo-Hyun Hwang ◽

Eun-Jin Park ◽

Jung-Hyun Kim ◽

Sung-Weon Ryoo

Keyword(s):

Clomiphene Citrate ◽

Treatment Success ◽

In Vitro Study ◽

Drug Efficacy ◽

Mycobacterium Abscessus ◽

Pulmonary Infections ◽

Wild Type ◽

Antimicrobial Drugs ◽

Resistant Strains

Mycobacterium abscessus (M. abscessus) causes chronic pulmonary infections and is the most difficult non-tuberculous mycobacteria (NTM) to treat due to its resistance to current antimicrobial drugs, with a treatment success rate of 45.6%. Thus, novel treatment drugs are needed, of which we identified the drug clomiphene citrate (CC), known to treat infertility in women, to exhibit inhibitory activity against M. abscessus. To assess the potential of CC as a treatment for M. abscessus pulmonary diseases, we measured its efficacy in vitro and established the intracellular activity of CC against M. abscessus in human macrophages. CC significantly inhibited the growth of not only wild-type M. abscessus strains but also clinical isolate strains and clarithromycin (CLR)-resistant strains of M. abscessus. CC’s drug efficacy did not have cytotoxicity in the infected macrophages. Furthermore, CC worked in anaerobic non-replicating conditions as well as in the presence of biofilm. The results of this in vitro study on M. abscessus activity suggest the possibility of using CC to develop new drug hypotheses for the treatment of M. abscessus infections.

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Shear bond strength evaluation of bonded molar tubes on fluorotic molars

The Angle Orthodontist ◽

10.2319/030812-203.1 ◽

2012 ◽

Vol 83 (1) ◽

pp. 152-157 ◽

Cited By ~ 6

Author(s):

Erika L. Silva-Benítez ◽

Veronica Zavala-Alonso ◽

Gabriel A. Martinez-Castanon ◽

Juan P. Loyola-Rodriguez ◽

Nuria Patiño-Marin ◽

...

Keyword(s):

Bond Strength ◽

Shear Bond Strength ◽

Dental Fluorosis ◽

In Vitro Study ◽

Mean Value ◽

Fixed Appliance ◽

Adhesive Remnant Index ◽

The Mean ◽

Electronic Microscope

Abstract Objective: To study the shear bond strength (SBS), sites of failure, and micromorphology of bonded molar tubes used on teeth affected by dental fluorosis. Materials and Methods: This in vitro study included 140 first molars classified according to Dean's index for dental fluorosis. Samples were divided into seven groups: (1) healthy teeth etched for 15 seconds, (2) teeth with moderate fluorosis (MOF) etched for 15 seconds, (3) teeth with MOF etched for 150 seconds, (4) teeth with MOF microabrasion etched for 15 seconds, (5) teeth with severe fluorosis (SEF) etched for 15 seconds, (6) teeth with SEF etched for 150 seconds, and (7) teeth with SEF microabrasion etched for 15 seconds. All samples were incubated and were then submitted to the SBS test and evaluated with the modified adhesive remnant index (ARI) and analyzed by using a scanning electronic microscope. Results: The SBS mean value for healthy enamel was 20 ± 10.2 MPa. For the group with MOF, the etched 150-second mean value was the highest (19 ± 7.6 MPa); for the group with SEF treated with microabrasion and etched for 15 seconds, the mean value was (13 ± 4.1 MPa). Significant differences (P ≤ .05) were found in the ARI between healthy and fluorosed groups. Conclusions: Fluorotic enamel affects the adhesion of bonded molar tubes. The use of overetching in cases of MOF and the combination of microabrasion and etching in SEF provides a suitable adhesion for fixed appliance therapy.

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An in vitro comparison of the force decay generated by different commercially available elastomeric chains and NiTi closed coil springs

Brazilian Oral Research ◽

10.1590/s1806-83242007000100009 ◽

2007 ◽

Vol 21 (1) ◽

pp. 51-57 ◽

Cited By ~ 23

Author(s):

Ana Cristina Soares Santos ◽

André Tortamano ◽

Sandra Regina Frazatto Naccarato ◽

Gladys Cristina Dominguez-Rodriguez ◽

Julio Wilson Vigorito

Keyword(s):

Artificial Saliva ◽

Testing Machine ◽

In Vitro Study ◽

Original Length ◽

Force Decay ◽

Decay Pattern ◽

The Mean ◽

Initial Force ◽

Elastomeric Chains

This in vitro study was designed to compare the forces generated by commercially available elastomeric chains and NiTi closed coil springs, and to determine their force decay pattern. Forty elastomeric chains and forty NiTi closed coil springs were divided into 4 groups according to the following manufacturers: (1) Morelli®, (2) Abzil®, (3) TP Orthodontics® and (4) American Orthodontics®. The specimens were extended to twice their original length and stored in artificial saliva at 37°C. Initial force was measured by means of an Instron universal testing machine and then at 1, 4, 7, 14, 21, and 28 days. The results revealed that the elastomeric chains delivered a mean initial force of 347 g for Morelli®, 351 g for American Orthodontics®, 402 g for Abzil®, and 404 g for TP Orthodontics®. The NiTi closed coil springs generated a mean initial force of 196 g for American Orthodontics®, 208 g for TP Orthodontics®, 216 g for Abzil®, and 223 g for Morelli®. The mean percentage of force decay observed after 28 days for the elastomeric chains was 37.4% for TP Orthodontics®, 48.1% for American Orthodontics®, 65.4% for Morelli®, and 71.6% for Abzil®. After 28 days, the NiTi closed coil springs presented a mean percentage of force decay of 22.6% for American Orthodontics®, 29.8% for Abzil®, 30.6% for Morelli®, and 45.8% for TP Orthodontics®. At the end of the study, significant differences were observed between the elastomeric chains and the NiTi closed coil springs. The results indicated that the studied NiTi closed coil springs are more adequate for dental movement than the elastomeric chains.

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In vitro and intracellular activity of imipenem combined with tedizolid, rifabutin, and avibactam against Mycobacterium abscessus

10.1101/411181 ◽

2018 ◽

Cited By ~ 2

Author(s):

Eva Le Run ◽

Michel Arthur ◽

Jean-Luc Mainardi

Keyword(s):

Inhibitory Concentration ◽

Antibacterial Activities ◽

Mycobacterium Abscessus ◽

Pulmonary Infections ◽

Once Daily ◽

Minimal Inhibitory Concentrations ◽

Recommended Treatment ◽

The Impact ◽

Lactamase Inhibitor

Mycobacterium abscessus has emerged as a significant pathogen responsible for chronic pulmonary infections in cystic fibrosis (CF) patients, which are difficult to treat due to resistance to a broad range of antibiotics. The initial phase of the recommended treatment in CF patients includes imipenem used without any β-lactamase inhibitor in spite of the production of the β-lactamase BlaMab. Here, we determine whether the addition of tedizolid, a once-daily oxazolidinone, improves the activity of imipenem alone or in combination with a β-lactamase inhibitor, avibactam, and rifabutin.The activity of the drugs was evaluated against M. abscessus CIP104536 by determining in vitro and intracellular antibacterial activities. The impact of BlaMab inhibition by avibactam on antibiotic activity was assessed by comparing CIP104536 and its β-lactamase-deficient derivative (ΔblaMab).The minimal inhibitory concentrations (MICs) of tedizolid against M. abscessus CIP104536 and ΔblaMab were 4 μg/mL. Tedizolid combined with imipenem showed a moderate synergistic effect with fractional inhibitory concentration (FIC) indexes of 0.41 and 0.38 for CIP104536 and ΔblaMab, respectively. For both strains, the addition of tedizolid at 2 μg/mL, corresponding to the peak serum concentration, increased the intracellular efficacy of imipenem at 8 and 32 μg/mL. Addition of avibactam and rifabutin improved the activity of the imipenem-tedizolid combination against CIP104536S.The imipenem-tedizolid combination should be further considered for the treatment of M. abscessus pulmonary infections in CF patients. The efficacy of the treatment might benefit from the use of a β-lactamase inhibitor, such as avibactam, and the addition of rifabutin.

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Evaluation of Gaps or Voids Occurring in Roots Filled with Three Different Sealers

European Journal of Dentistry ◽

10.1055/s-0039-1697817 ◽

2010 ◽

Vol 04 (02) ◽

pp. 101-109 ◽

Cited By ~ 5

Author(s):

Melek Akman ◽

Serhan Akman ◽

Oznur Derinbay ◽

Sema Belli

Keyword(s):

In Vitro Study ◽

Gutta Percha ◽

Rotary Instruments ◽

Single Cone ◽

Ah Plus ◽

Root Dentin ◽

The Mean ◽

Free Interfaces ◽

Niti Rotary Instruments

Objectives: The purpose of this in vitro study was to evaluate gaps or voids occurring in roots filled with three different sealers.Methods: Thirty extracted human single-rooted teeth were decoronated, instrumented using NiTi rotary instruments, divided into three groups (n=10 per group) and obturated with one of the following: Epiphany with Resilon, MetaSEAL with gutta-percha or AH Plus with gutta-percha using the match-taper single-cone technique. After storage for one week in 100% humidity at 37°C, the teeth were horizontally sectioned (n=10). Photographs were taken from the coronal, median and apical parts of the roots using a stereomicroscope at 10X magnification, and the images were then transferred to a computer. The mathematical method known as the ‘Affine Transformation’ was used for the transformation of pixel coordinates to ground coordinates in the Netcad Software program. The mean areas (μm2) of the gaps between the sealer and root dentin or gutta percha/resilon and the gaps between the sealer and/or voids inside the sealer mass were measured, scored on a 0-3 scale and statistically analyzed with the Kruskal-Wallis test.Results: The mean total area of gaps or voids for each sealer was 4631.80 μm2 for the Epiphany- Resilon, 3826.80 μm2 for the MetaSEAL-gutta-percha and 31334 μm2 for the AH Plus-gutta-percha. The MetaSEAL-gutta-percha group showed more gap or void-free interfaces. No significant differences were found among the sealers in the scores for the gap areas (P<.05), and the MetaSEAL showed similar interfaces with Epiphany.Conclusions: No significant differences in the mean areas of gaps or voids were found among the tested resin-based sealers. (Eur J Dent 2010;4:101-109)

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Inhibition of Demineralization at Restoration Margins of Z100 and Tetric EvoCeram Bulk Fill in Dentin and Enamel

Bioengineering ◽

10.3390/bioengineering6020036 ◽

2019 ◽

Vol 6 (2) ◽

pp. 36

Author(s):

Cristina Leon-Pineda ◽

Kevin Donly

Keyword(s):

Light Microscopy ◽

Polarized Light ◽

In Vitro Study ◽

The Other ◽

Solution Ph ◽

Class V ◽

The Mean ◽

Student’S T ◽

Student’S T Test

Recurrent caries is still considered the main reason restorations need to be replaced. There are different materials available now that promise to reduce the possibility of recurrent caries by releasing fluoride and inhibiting restoration marginal caries. The purpose of this in vitro study was to evaluate the demineralization inhibition potential of a non-fluoride-releasing resin (Z100TM 3M, St. Paul, MN, USA) and a glass containing resin-based composite (Tetric EvoCeram Bulk Fill, Ivoclar/Vivadent AG, Schaan, Liechtenstein), which contains fluoride. Class V preparations were placed on 22 premolars; the gingival margin was below the cementoenamel junction and the occlusal margin was placed above the cemento-enamel junction. Ten teeth were randomly selected to be restored with Z100 while the other 10 were restored with Tetric EvoCeram Bulk Fill. Both groups were restored following manufacturer’s instructions. All teeth had an acid resistant varnish placed within one millimeter of the preparation margins. Both groups were placed in artificial caries challenge solution (pH 4.4). At the end of the 4 days; 100 µm buccolingual sections were obtained for each tooth; these were photographed under polarized light microscopy and the demineralized areas adjacent to the restorations were measured and quantified. The mean (±S.D.) area (µm2) of demineralization from the occlusal margin (enamel) and dentin margin were: Z100 2781.889 ± 1045.213; 3960.455 ± 705.964 and for Tetric EvoCeram Bulk Fill 1541.545 ± 1167.027; 3027.600 ± 512.078. Student’s t-test indicated that there was significantly less enamel and dentin demineralization adjacent to Tetric EvoCeram Bulk Fill compared to Z100; there was significantly less demineralization in enamel compared to dentin in both Tetric EvoCeral Bulk Fill and Z100. Tetric EvoCeram Bulk Fill performed better inhibiting demineralization at restoration margins when compared to Z100 and provided better demineralization inhibition in enamel than cementum/dentin.

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Effect of Different Intermediary Bases on Microleakage of a Restorative Material in Class II Box Cavities of Primary Teeth

The International Journal of Artificial Organs ◽

10.5301/ijao.5000566 ◽

2017 ◽

Vol 40 (2) ◽

pp. 82-87 ◽

Cited By ~ 1

Author(s):

Faika Y. Abdelmegid ◽

Fouad S. Salama ◽

Waleed M. Al-Mutairi ◽

Saud K. Al-Mutairi ◽

Sultan O. Baghazal

Keyword(s):

Primary Teeth ◽

In Vitro Study ◽

Class Ii ◽

Positive Control ◽

Negative Control ◽

The Other ◽

Control Groups ◽

Significant Difference ◽

The Mean

Introduction The aim of this in vitro study was to assess and compare the effect of different intermediary bases on microleakage between tooth and a nanocomposite interface in Class II box cavities in primary teeth. Methods Standard Class II box cavities were prepared in 52 primary molars and randomly divided into 9 groups according to the intermediary base used (Multicore Flow, Fuji II LC, SDR, Smart Dentin Replacement, and Biodentine). All specimens were subjected to thermocycling and prepared for microleakage testing and evaluation. Results There was significant difference in the mean ranks of microleakage between the 9 groups, which was observed in the gingival side (p<0.0001) and the occlusal side (p<0.0001). The mean ranks microleakage was significantly higher with experimental SDR, experimental Multicore Flow, and positive control materials when compared with the other 6 groups. The microleakage mean ranks were statistically significantly lower in experimental Fuji II LC, experimental Biodentine, and all negative control groups when compared with the other 3 groups. Conclusions Microleakage is affected by the application of intermediate material. Experimental Biodentine and Fuji II LC showed the lowest microleakage while experimental SDR and experimental Multicore Flow showed the highest microleakage.

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Select β-Lactam Combinations Exhibit Synergy againstMycobacterium abscessus In Vitro

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02613-18 ◽

2019 ◽

Vol 63 (4) ◽

Cited By ~ 15

Author(s):

Elizabeth Story-Roller ◽

Emily C. Maggioncalda ◽

Gyanu Lamichhane

Keyword(s):

Treatment Options ◽

Unmet Need ◽

Mycobacterium Abscessus ◽

Nontuberculous Mycobacterium ◽

Pulmonary Infections ◽

Content Type ◽

Resistant Mutants ◽

Lactamase Inhibitor ◽

Selection Of

ABSTRACTMycobacterium abscessusis a nontuberculous mycobacterium that causes invasive pulmonary infections in patients with structural lung disease.M. abscessusis intrinsically resistant to several classes of antibiotics, and an increasing number of strains isolated from patients exhibit resistance to most antibiotics considered for treatment of infections by this mycobacterium. Therefore, there is an unmet need for new regimens with improved efficacy to treat this disease. Synthesis of the essential cell wall peptidoglycan inM. abscessusis achieved via two enzyme classes,l,d- andd,d-transpeptidases, with each class preferentially inhibited by different subclasses of β-lactam antibiotics. We hypothesized that a combination of two β-lactams that comprehensively inhibit the two enzyme classes will exhibit synergy in killingM. abscessus. Paired combinations of antibiotics tested forin vitrosynergy againstM. abscessusincluded dual β-lactams, a β-lactam and a β-lactamase inhibitor, and a β-lactam and a rifamycin. Of the initial 206 combinations screened, 24 pairs exhibited synergy. A total of 13/24 pairs were combinations of two β-lactams, and 12/24 pairs brought the MICs of both drugs to within the therapeutic range. Additionally, synergistic drug pairs significantly reduced the frequency of selection of spontaneous resistant mutants. These novel combinations of currently available antibiotics may offer viable immediate treatment options against highly-resistantM. abscessusinfections.

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Evaluation of marginal fit of two allceramic copings with two finish lines

European Journal of Dentistry ◽

10.1055/s-0039-1698946 ◽

2012 ◽

Vol 06 (02) ◽

pp. 163-168 ◽

Cited By ~ 17

Author(s):

Gulce Subasi ◽

Nilgun Ozturk ◽

Inan Ozgur ◽

Nalan Bozogullari

Keyword(s):

Stainless Steel ◽

Analysis Of Variance ◽

In Vitro Study ◽

Finish Line ◽

Marginal Fit ◽

Luting Agent ◽

All Ceramic ◽

The Mean ◽

Line Design

ABSTRACTObjectives: This in-vitro study investigated the marginal fit of two all-ceramic copings with 2 finish line designsMethods: Forty machined stainless steel molar die models with two different margin designs (chamfer and rounded shoulder) were prepared. A total of 40 standardized copings were fabricated and divided into 4 groups (n=10 for each finish line-coping material). Coping materials tested were IPS e.max Press and Zirkonzahn; luting agent was Variolink II. Marginal fit was evaluated after cementation with a stereomicroscope (Leica MZ16). Two-way analysis of variance and Tukey-HSD test were performed to assess the influence of each finish line design and ceramic type on the marginal fit of 2 all-ceramic copings (α =.05) Results: Two-way analysis of variance revealed no statistically significant differences for marginal fit relative to finish lines (P=.362) and ceramic types (P=.065)Conclusion: Within the limitations of this study, both types of all-ceramic copings demonstrated that the mean marginal fit was considered acceptable for clinical application (≤120 μm). (Eur J Dent 2012;6:163-168)

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Influence of Orthodontic Anchor Screw Anchorage Method on the Stability of Artificial Bone: An In Vitro Study

Materials ◽

10.3390/ma13143205 ◽

2020 ◽

Vol 13 (14) ◽

pp. 3205 ◽

Cited By ~ 2

Author(s):

Seen-Young Kang ◽

Ji-Min Yu ◽

Hyoung-Sik Kim ◽

Jun-Seok Lee ◽

Chan-Mi Yeon ◽

...

Keyword(s):

In Vitro Study ◽

Automatic Device ◽

Insertion Torque ◽

Artificial Bone ◽

Artificial Bones ◽

Significant Difference ◽

The Mean ◽

The Stability ◽

Torque Values

This study aims to compare the torque values for various lengths of the titanium-based orthodontic anchor screw (OAS), different anchorage methods and varying artificial bone densities after predrilling. Furthermore, the effects of these parameters on bone stability are evaluated. A total of 144 OASs were prepared with a diameter of 1.6 mm and heights of 6, 8 and 10 mm. Artificial bones were selected according to their density, corresponding to Grades 50, 40 and 30. Torque values for the automatic device and manual anchorage methods exhibited a statistically significant difference for the same-sized OAS, according to the bone density of the artificial bones (p < 0.05). However, when insertion torque was at the maximum rotations, there was no significant difference in the torque values for the Grade 30 artificial bone (p > 0.05). When the torque values of both anchorage methods were statistically compared with the mean difference for each group, the results of the manual anchorage method were significantly higher than those of the automatic device anchorage method (p < 0.05). A statistically significant difference was observed in the bone stability resulting from different OAS anchorage methods and artificial bone lengths. These findings suggest that the automatic anchorage method should be used when fixing the OAS.

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