Activated carbon fiber as an efficient co-catalyst toward accelerating Fe2+/Fe3+ cycling for improved removal of antibiotic cefaclor via electro-Fenton process using a gas diffusion electrode.

The electro-Fenton (EF) based on gas-diffusion electrodes (GDEs) reveals promising application prospective towards recalcitrant organics degradation because such GDEs often yields superior H2O2 generation efficiency and selectivity. However, the low efficiency of Fe2+/Fe3+ cycle with GDEs is always considered to be the limiting step for the EF process. In this study, activated carbon fiber (ACF) was firstly employed as co-catalyst to facilitate the performance of antibiotic cefaclor (CEC) decomposition in EF process. It was found that the addition of ACF co-catalyst achieved a rapid Fe2+/Fe3+ cycling, which significantly enhanced Fenton's reaction and hydroxyl radicals (•OH) generation. X-ray photoelectron spectroscopy (XPS) results indicated that the functional groups on ACF surface are related to the conversion of Fe3+ into Fe2+. Moreover, DMSO probing experiment confirmed the enhanced •OH production in EF + ACF system compared to conventional EF system. When inactive BDD and Ti4O7/Ti anodes were paired to EF system, the addition of ACF could significantly improve mineralization degree. However, a large amount of toxic byproducts, including chlorate (ClO3-) and perchlorate (ClO4-), were generated in these EF processes, especially for BDD anode, due to their robust oxidation capacity. Higher mineralization efficiency and less toxic ClO4- generation were obtained in the EF + ACF process with Ti4O7/Ti anode. This presents a novel alternative for efficient chloride-containing organic removal during wastewater remediation.

Comparative study of two cephalosporin antibiotics binding to calf thymus DNA by multispectroscopy, electrochemistry, and molecular docking.

The over-use of antibiotics has caused a number of problems such as contamination of antibiotic residues and virus resistance, and therefore has attracted global attention. In this study, spectroscopic techniques and molecular docking were employed to predict conformational changes and binding interaction between two cephalosporins (cefaclor and cefixime) and calf thymus DNA (ctDNA). Fluorescence and UV-vis spectra suggested that static quenching was predominant and cephalosporin bound to the groove region of ctDNA. Binding parameters calculated by the Stern-Volmer and Scatchard equations showed that cephalosporin bound to ctDNA with a binding affinity in the order of 103  L mol-1 . Thermodynamic parameters further indicated that the reaction was a spontaneous process driven by enthalpy and entropy, and that the main binding force was an electrostatic force. The effects of iodide, denaturant, thermal denaturation and pH on a cephalosporin-Hoechst-DNA complex were also studied, and the results confirmed that cephalosporin bound to the groove area of DNA. Finally, these results were further confirmed by molecular docking and electrochemical studies.

Chromatographic studies of unusual on-column degradation of cefaclor observed in the impurity separation by HPLC.

An unpredictable ghost peak was intermittently observed during the impurity separation of cefaclor and formulation by high performance liquid chromatography (HPLC) with a content from below the reported threshold to approximately 0.3% in different laboratories. Through a series of investigations, the ghost peak was identified as an unusual on-column degradant of cefaclor formed under elevated column temperature but was not an actual sample impurity. The chemical structure of the degradant was determined by spectroscopic methods, including high resolution mass spectrometry (HRMS) and 1H-NMR. Consequently, the unknown peak was identified as a C-4 oxidative decarboxylation analog of cefaclor. The formation mechanism of the analog is proposed, and it is suggested that elevated column temperature during HPLC analysis has a profound effect on the degradation. Dissolved oxygen in the mobile phase may promote the formation of the ghost peak. The degradation can be suppressed by using a column temperature below 30 °C. Moreover, several other prevention measures are suggested based upon the results of the investigation.

Cytotoxicity of intracanal dressings on apical papilla cells differ upon activation with E. faecalis LTA.

OBJECTIVE: The aim of this study was to investigate the cytotoxic effects of modified triple antibiotic paste and an experimental composition using calcium hydroxide on lipoteichoic acid (LTA)-primed apical papilla cells (APC). MATERIAL AND METHODS: Human APC were tested for in vitro cytotoxicity of modified Triple Antibiotic Paste (mTAP - Ciprofloxacin, Metronidazole and Cefaclor at 1:1:1) and of a paste of Ciprofloxacin, Metronidazole and Calcium hydroxide (CMC - 1:1:2) and modified CMC (mCMC - 2:2:1) by using MTT assay. The substances were reconstituted in DMEM at 1,000 µg/mL and » serially diluted before being kept in contact with cells for 1, 3, 5 and 7 days. Further, cells were primed with 1 µg/mL of Enterococcus faecalis LTA for 7 days prior to the viability test with 1,000 µg/mL of each substance. Statistical analysis was performed using one-way analysis of variance (ANOVA) and two-way ANOVA respectively followed by Tukey's post-test. Significance levels were set at p<0.05. RESULTS: In the first assay, the higher cytotoxic rates were reached by mTAP for all experimental periods. CMC was found toxic for APC at 5 and 7 days, whereas mCMC did not affect the cell viability. Only CMC and mCMC were able to induce some cellular proliferation. In the second assay, when considering the condition with medium only, LTA-primed cells significantly proliferated in comparison to LTA-untreated ones. At this context, mTAP and CMC showed similar cytotoxicity than the observed for LTA-untreated cells, while mCMC was shown cytotoxic at 7 days only for LTA-primed APC. Comparing the medications, mTAP was more cytotoxic than CMC and mCMC. CONCLUSION: mTAP showed higher cytotoxicity than CMC and mCMC and the effect of topic antimicrobials might differ when tested against apical papilla cells under physiological or activated conditions.

Cytotoxicity of intracanal dressings on apical papilla cells differ upon activation with E. faecalis LTA

Abstract Objective The aim of this study was to investigate the cytotoxic effects of modified triple antibiotic paste and an experimental composition using calcium hydroxide on lipoteichoic acid (LTA)-primed apical papilla cells (APC). Material and Methods Human APC were tested for in vitro cytotoxicity of modified Triple Antibiotic Paste (mTAP - Ciprofloxacin, Metronidazole and Cefaclor at 1:1:1) and of a paste of Ciprofloxacin, Metronidazole and Calcium hydroxide (CMC - 1:1:2) and modified CMC (mCMC - 2:2:1) by using MTT assay. The substances were reconstituted in DMEM at 1,000 µg/mL and » serially diluted before being kept in contact with cells for 1, 3, 5 and 7 days. Further, cells were primed with 1 µg/mL of Enterococcus faecalis LTA for 7 days prior to the viability test with 1,000 µg/mL of each substance. Statistical analysis was performed using one-way analysis of variance (ANOVA) and two-way ANOVA respectively followed by Tukey's post-test. Significance levels were set at p<0.05. Results In the first assay, the higher cytotoxic rates were reached by mTAP for all experimental periods. CMC was found toxic for APC at 5 and 7 days, whereas mCMC did not affect the cell viability. Only CMC and mCMC were able to induce some cellular proliferation. In the second assay, when considering the condition with medium only, LTA-primed cells significantly proliferated in comparison to LTA-untreated ones. At this context, mTAP and CMC showed similar cytotoxicity than the observed for LTA-untreated cells, while mCMC was shown cytotoxic at 7 days only for LTA-primed APC. Comparing the medications, mTAP was more cytotoxic than CMC and mCMC. Conclusion mTAP showed higher cytotoxicity than CMC and mCMC and the effect of topic antimicrobials might differ when tested against apical papilla cells under physiological or activated conditions.

Coordination and redox interactions of ß-lactam antibiotics with Cu2+ in physiological settings and the impact on antibacterial activity.

An increase in the copper pool in body fluids has been related to a number of pathological conditions, including infections. Copper ions may affect antibiotics via the formation of coordination bonds and/or redox reactions. Herein, we analyzed the interactions of Cu2+ with eight ß-lactam antibiotics using UV-Vis spectrophotometry, EPR spectroscopy, and electrochemical methods. Penicillin G did not show any detectable interactions with Cu2+. Ampicillin, amoxicillin and cephalexin formed stable colored complexes with octahedral coordination environment of Cu2+ with tetragonal distortion, and primary amine group as the site of coordinate bond formation. These ß-lactams increased the solubility of Cu2+ in the phosphate buffer. Ceftazidime and Cu2+ formed a complex with a similar geometry and gave rise to an organic radical. Ceftriaxone-Cu2+ complex appears to exhibit different geometry. All complexes showed 1:1 stoichiometry. Cefaclor reduced Cu2+ to Cu1+ that further reacted with molecular oxygen to produce hydrogen peroxide. Finally, meropenem underwent degradation in the presence of copper. The analysis of activity against Escherichia coli and Staphylococcus aureus showed that the effects of meropenem, amoxicillin, ampicillin, and ceftriaxone were significantly hindered in the presence of copper ions. The interactions with copper ions should be taken into account regarding the problem of antibiotic resistance and in the selection of the most efficient antimicrobial therapy for patients with altered copper homeostasis.

Battling bacterial infection with hexamethylene diisocyanate cross-linked and Cefaclor-loaded collagen scaffolds.

Implant infections remain a major healthcare problem due to the prolonged hospitalisation period required to disrupt and treat bacterial biofilm formation, and the need for additional surgery to remove/replace the infected implant, which if not removed in a timely manner may lead to sepsis. Although localised drug administration, via an implanted scaffold, has shown promise in a clinical setting, the ideal scaffold cross-linking (to initially withstand the aggressive infection environment) and drug (to be effective against infection) have yet to be identified. In this work, in the first instance, the biochemical, biophysical, and biological properties of collagen sponges as a function of various concentrations (0.625%, 1.0%, 2.5%, 5.0%, and 10.0%) of hexamethylene diisocyanate were assessed. Data presented illustrate that hexamethylene diisocyanate at 0.625% concentration was able to effectively stabilise collagen scaffolds, as judged by the reduction in free amines, adequate resistance to collagenase digestion, reduction in swelling, increase in denaturation temperature, suitable mechanical properties, and appropriate cytocompatibility. Subsequently, collagen scaffolds stabilised with 0.625% hexamethylene diisocyanate were loaded with variable concentrations (0, 10, 100, and 500 µg ml-1) of Cefaclor and Ranalexin. Both drugs exhibited similar loading efficiency, release profile, and cytocompatibility. However, only collagen scaffolds loaded with 100 µg ml-1 Cefaclor exhibited adequate antibacterial properties against both 106 and 108 colony-forming units per ml of both Escherichia coli and Staphylococcus epidermidis.

Mass Spectral Profile for Rapid Differentiating Beta-Lactams from Their Ring-Opened Impurities.

High performance liquid chromatography tandem mass spectrometry (HPLC MS) has been widely used for ß-lactam antibiotics determination. However, its application to identify impurities of these frequently used drugs is not sufficient at present. In this job, characteristic profiles of the collision induced dissociation (CID) spectra of both ß-lactams and ring-opened ß-lactams were extracted from the MS data of six ß-lactam antibiotics and their forty-five impurities, and were confirmed by the MS data reported in the literature. These characteristics have been successfully applied to rapid differentiation of ß-lactam and ring-opened ß-lactam impurities in cefixime, cefdinir, and cefaclor. However, these characteristic profiles can only be obtained under low activating voltage. They did not display in the high energy activated CID spectra. Diagnostic fragmentations for determining the localization of double bond and substituents on the thiazine ring and the side chain were also observed. In addition, several characteristic fragmentations are hopeful to be used to differentiate the configurations of C-2 on the thiazine ring of ring-opened impurities, which is generally disadvantageous of mass spectrometry. Taken together, forty-five impurities were identified from the capsules of cefixime, cefdinir, and cefaclor.

Comparison of bond strength of self-etch adhesive to pulp chamber dentin after placement of calcium hydroxide and various antibiotic pastes.

OBJECTIVE: The aim of this study was to evaluate the effect of calcium hydroxide, double antibiotic paste (DAP) and triple antibiotic paste (TAP) with minocycline, cefaclor and amoxicillin on the micro tensile bond strength (µTBS) of self-etch adhesive to pulp chamber dentin. MATERIALS AND METHODS: Sixty mandibular first molars were cut horizontally and randomly divided into a control group and five experimental groups, which received an intra-canal dressing, as follows: calcium hydroxide, DAP, TAP with minocycline, TAP with cefaclor and TAP with amoxicillin. After storing the specimens for 4 weeks, the medicaments were removed by irrigation with 10 mL each of the following solution: 2.5% NaOCl, 17% EDTA and distilled water. A self-etch adhesive (Clearfil S3 Bond, Okayama, Japan) was applied and composite resin (Clearfil Majesty Posterior, Kuraray Medical Inc., Japan) was placed into the cavity. A µTBS test was performed on each specimen using a universal test machine. RESULTS: The DAP reduced the µTBS of self-etch adhesive compared to the control group, calcium hydroxide and TAP with minocycline and with cefaclor (p < 0.05). However, the other medicaments did not result in a decreased µTBS of self-etch adhesive to pulp chamber dentin as compared to the control group (p > 0.05). CONCLUSIONS: The use of DAP resulted in a reduced µTBS of self-etch adhesive to pulp chamber dentin.

Covalent inhibition of New Delhi metallo-ß-lactamase-1 (NDM-1) by cefaclor.

Covalent irreversible inhibitors can successfully treat antibiotic-resistant infections by targeting serine ß-lactamases. However, this strategy is useless for New Delhi metallo-ß-lactamase (NDM), which uses a non-covalent catalytic mechanism and lacks an active-site serine. Here, NDM-1 was irreversibly inactivated by three ß-lactam substrates: cephalothin, moxalactam, and cefaclor, albeit at supratherapeutic doses (e.g., cefaclor KI =2.3 ± 0.1 mM; k(inact) =0.024 ± 0.001 min(-1)). Inactivation by cephalothin and moxalactam was mediated through Cys208. Inactivation by cefaclor proceeded through multiple pathways, in part mediated by Lys211. Use of a cefaclor metabolite enabled mass spectrometric identification of a +346.0735 Da covalent adduct on Lys211, and an inactivation mechanism is proposed. Lys211 was identified as a promising "handhold" for developing covalent NDM-1 inhibitors and serves as a conceptual example for creating covalent inhibitors for enzymes with non-covalent mechanisms.

The effect of medicaments used in endodontic regeneration technique on the dislocation resistance of mineral trioxide aggregate to root canal dentin.

INTRODUCTION: The aim of this study was to evaluate the effect of calcium hydroxide (CH) and antibiotic pastes, including a mixture of metronidazole and ciprofloxacin, with and without minocycline or cefaclor, on the dislocation resistance of mineral trioxide aggregate (MTA) to root dentin. METHODS: Eighty single-rooted human mandibular premolars were selected. The teeth were prepared by using the ProTaper system. The prepared teeth were then instrumented to a #6 Peeso reamer to obtain a standard internal diameter of 1.5 mm. The reamers were passed 1 mm beyond apex to simulate immature teeth. The specimens were then randomly divided into a control group (no intracanal medicament was used) and 4 experimental groups that were treated with an intracanal medicament: CH, double antibiotic paste (DAP) with metronidazole and ciprofloxacin, triple antibiotic paste (TAP) with minocycline, or TAP with cefaclor (n = 16). After 3 weeks, the medicaments were removed, and approximately 3 mm of MTA was placed in the coronal third of the canals. A push-out test was used to measure the dislocation resistance between the root dentin and MTA. Data were analyzed by using one-way analysis of variance and Tukey post hoc tests. RESULTS: The dislocation resistance values of the CH, TAP with minocycline, and TAP with cefaclor groups were similar to those of the control group (P > .05), whereas the DAP group had the lowest dislocation resistance when compared with the other groups (P < .05). Overall, there was a predominance of cohesive failures between root dentin and MTA. CONCLUSIONS: The results of this study indicate that the application of DAP as an intracanal medicament reduced the dislocation resistance of MTA to root dentin.

Determination of cefaclor by UPLC-MS-MS for a Chinese pharmacokinetic study.

A novel method has been developed for the determination of cefaclor in human plasma by ultra-performance liquid chromatography combined with tandem mass spectrometry (UPLC-MS-MS). The plasma was treated by a single step of protein precipitation with acetonitrile. The chromatographic separation was performed on a Waters Acquity UPLC BEH C18 (2.1 × 100 mm, 1.7 µm) with a gradient mobile phase consisting of 0.1% formic acid and acetonitrile at a flow rate of 0.4 mL/min. The analyses were conducted by multiple reaction monitoring using the precursor-to-product combinations of m/z 367.5 → 173.8 (cefaclor) and m/z 454.1 → 160.3 (internal standard). Validation results indicated that the lower limit of quantification was 2 ng/mL and the assay exhibited a linear range of 2-10,000 ng/mL. Quality control samples (5, 200 and 5,000 ng/mL) in five replicates from three different runs of analysis demonstrated an intra-assay precision (relative standard deviation) of 3.7-10.7%, an inter-assay precision of 5.8-8.9%, and an overall accuracy of < 15%. A sensitive and specific method for quantifying cefaclor in human plasma has been devised and successfully applied to a pharmacokinetic study.

Structures of cefradine dihydrate and cefaclor dihydrate from DFT-D calculations.

The crystal structure of cefradine dihydrate, C16H19N3O4S·2H2O, is considered in the pharmaceutical sciences to be the epitome of an isolated-site hydrate. The structure from single-crystal X-ray data was described in 1976, but atomic coordinates were not published. The atomic coordinates are determined here by combining the information available from the published single-crystal data with a dispersion-corrected density functional theory (DFT-D) method that has been validated to reproduce molecular crystal structures very accurately. Additional proof for the correctness of the structure comes from comparison with cefaclor dihydrate, C15H14ClN3O4S·2H2O, which is isomorphous and for which more complete single-crystal data are available. H-atom positions have not previously been published for either compound. The DFT-D calculations confirm that both cefradine and cefaclor are present in the zwitterionic form in the two dihydrate structures. A potential ambiguity concerning the orientation of the cyclohexadienyl ring in cefradine dihydrate is also clarified, and on the basis of the calculated energies it is shown that disorder should not be expected at room temperature. The DFT-D methods can be applied to recover full structural data in cases where only partial information is available, and where it may not be possible or desirable to obtain new experimental data.

Synthesis, magnetic and spectroscopic studies of a Schiff base derived from cephaclor and 1,2-diaminobenzene and its transition metal complexes.

M(II) coordination compounds of Mn, Fe, Co and Ni with a Schiff base (HL) derived from the condensation of cephaclor antibiotic with 1,2-diaminobenzene were synthesized and characterized by several techniques, including elemental and thermal analysis, molar conductance and magnetic susceptibility measurements, electronic, FT-IR, EPR and (1)H NMR spectral studies. The analytical and molar conductance values indicated that the chloride ions coordinate to the metal ions. Based on these studies, the general formulae [M(L)Cl(H2O)] (M(II)=Mn, Fe, Co, Ni) are proposed for the complexes. The ligand HL behaves as a monoanionic tetradentate NNNO chelating agent.

Development of coated beads for oral controlled delivery of cefaclor: In vitro evaluation.

The aim of the present study was to develop and characterize coated chitosan-alginate beads containing cefaclor as a controlled release delivery system. Coated cefaclor beads were prepared by solvent evaporation techniques. Beads were found to be intact and spherical in shape. Their size range was 1.05 to 2.06. The loading efficiency showed maximum value when the concentration of cefaclor, chitosan and PEG 400 was 10 % (m/V), 0.5 % (m/V) and 2 % (V/V), respectively. Best retardation of cefaclor release from chitosan-alginate beads was achieved by coating with 15 % of shellac in formula F19. A significant antimicrobial activity (p < 0.05) against Staphylococcus aureus and Klebsiella pneumoniae was observed for formula F19 compared to the standard antibiotic disc. Furthermore, the simulated plasma profile showed the superiority of F19 in sustaining drug release for more than 12 h. Therefore, shellac coated chitosan-alginate beads could be considered a successful controlled release oral cefaclor dosage form.

Solid phase extraction and determination of Cr(III) by spectrophotometry using cefaclor as a complexing reagent and FAAS.

The present study reports on the application of modified groundnut shell as a new, easily prepared, and stable sorbent for the extraction of trace amount of Cr(III) in aqueous solution. 2-Hydroxybenzaldiminoglycine was immobilized on groundnut shells in alkaline medium and then used as a solid phase for the column preconcentration of Cr(III). The elution was carried out with 3 mL of 2 mol L(-1) HCl. The amount of eluted Cr(III) was determined by spectrophotometry using cefaclor as a complexing reagent and by flame atomic absorption spectrometry (FAAS). Different experimental variables such as pH, amount of solid sorbent, volume and concentration of eluent, sample and eluent flow rate, and interference of other metal ions on the retention of Cr(III) were studied. Under the optimized conditions, the calibration curves were found to be linear over the concentration range of 13-104 and 10-75 µg L(-1) with a detection limit of 3.64 and 1.24 µg L(-1) for spectrophotometric method and FAAS, respectively. An enrichment factor of 200 and RSD of ±1.19-1.49 % for five successive determinations of 25 µg L(-1) were achieved. The column preconcentration was successfully applied to the analysis of tap water and underground water samples.

Bioequivalence studies of 2 oral cefaclor capsule formulations in chinese healthy subjects.

An open-label, single-dose, randomized, crossover study was carried out in 20 Chinese healthy male subjects to compare the pharmacokinetics of 2 cefaclor (CAS 53994-73-3) formulations after administration of a single 250 mg dose of each drug with a 1-week wash-out period. Blood samples were collected before and with 6 h after drug administration. Plasma concentrations were determined by high-performance liquid chromatography (HPLC) with UV detector. 2 formulations were evaluated using the following pharmacokinetic parameters: AUC0-t, Cmax and tmax was analyzed nonparametrically. The 90% confidence interval (CI) of the ratios (teat/reference) of log-transformed AUC0-t and Cmax fell within the bioequivalence acceptance range of 80-125%. The results showed that the 90% CI of the ratios of AUC0-t and Cmax were 105.1% (101.0-109.4%) and 92.4% (82.5-103.4%), respectively, which therefore could conclude 2 oral cefaclor capsule formulations of cefaclor are bioequivalent. Both treatments showed similar tolerability and safety.

Evaluation of cefaclor oral suspensions stability using reversed phase high performance liquid chromatography and antimicrobial diffusion methods.

The effect of temperature stresses on Cefaclor suspensions under different storage conditions for a duration of 14 days was tested. The degradation of Cefaclor was determined on the 2nd, 7th and 14th day after reconstitution using a sensitive and precise Reversed phase High Performance Liquid Chromatographic (RP-HPLC) method. The RSD values for Forticef, Midocef, Ceclor, Cefabac and Cloracef, indicated a good precision of the RP-HPLC method. The limit of detection (LOD) and the limit of quantification (LOQ) were found 0.008 mg/ml and 0.03mg/ml respectively. The antimicrobial effect of Cefaclor suspension was also tested against pathogenic bacteria using the cylinder diffusion method. The RSD values range of the antimicrobial assay for all the Cefaclor compounds were 1.47-3.7%. The LOD and LOQ were 0.2mg/ml and 1mg/ml respectively. During the normal use of Ceclor, Midocef, and Forticef the loss of activity and the degradation were less than 5% on the 14th day of preservation at 4°C. However, the percentage of degradation for Cefabac and Cloracef on the 14th day reached 5 and 6%, respectively. Statistical multiple comparison between the effect of 4°C and 25°C indicated non significant mean differences (P>0.05) for Forticef, Cefabac, Ceclor and Cloraf and significant effect for Midocef (P <0.05). Significant effects were observed between (4oC and 37°C) and (25°C and 37°C) for all except Ceclor. Multiple comparisons between days of storage showed non significant mean difference values at 4°C except Cefabac. However significant results between days were found at 25°C and 37°C except for Midocef between (7th and 14th day). It was found that the pediatric suspensions of Cefaclor in the Jordanian market were stable and contained the amount of active ingredient specified by the United States pharmacopoeias specification (USP) and the British Pharmacopoeias specifications (BP).