Erythromycin Research Articles

Exploring the combination characteristics of dissolved organic matter with erythromycin in a soil infiltration system

ABSTRACT Erythromycin (ERY), as a common macrolides antibiotic, is widely used for sterilisation and disinfection of humans or livestock whose migration and transformation in the surface water environment are significantly related to dissolved organic matter (DOM). The characteristics of DOM can be greatly influenced by the complexation between ERY with itself in soil infiltration system. Using spectroscopic techniques (excitation-emission matrices, parallel factor analysis, Fourier infrared spectroscopy, and synchronous fluorescence spectroscopies) to explore the complexation properties of each DOM component with ERY in the system. The binding order of ERY with DOM functional groups was determined by two-dimensional correlation spectroscopy combined with FTIR. The amide I band v(C = O) exhibited stronger binding affinity. After the treatment, the DOM fluorescence intensity sharply decreased and the ERY concentration declined by 88.36%. Thus, synchronous degradation may occur between them. The result of synchronous fluorescence spectroscopy integrated with two-dimensional correlation spectroscopy indicated that the complexation sequencing and ability of DOM with ERY can be changed by a soil infiltration system. There are more binding sites exhibited in DOM with ERY in effluent than influent. A protein-like component of DOM showed priority binding order and more stable binding with ERY and had the highest Log KM value of 3.61. These results demonstrated that the binding of DOM with ERY in a soil infiltration system could take out most fluorescent DOM, and reduce the concentration and risk of ERY in the surface water body.

Adsorption of antibiotics on montmorillonite and site energy distribution analysis

The migration and transformation of antibiotics requires further study in geochemical settings. In this study, the removal effect of montmorillonite (Mt) on antibiotics was investigated, using the broad-spectrum antibiotics ciprofloxacin (CIP) and erythromycin (ERY) as subjects. The results of adsorption kinetics and adsorption isotherm experiments showed that the generalized Langmuir model describe the adsorption process well, and the adsorption capacity of CIP was higher. The intercalation and adsorption behaviors of CIP and ERY on Mt surface were analyzed by FT-IR, SEM, TEM, XRD and Molecular simulation. In order to analyze the different adsorption capacity of these antibiotics on Mt, the theory of site energy distribution was employed. By fitting the experimental data with the Generalized-Langmuir model, the site energy distribution and average site energy were calculated, which revealed the competitive adsorption mechanism of CIP and ERY on Mt. Moreover, the adsorption of antibiotics on Mt under different pH conditions was studied, and the competitive adsorption results were also demonstrated by the potential energy distribution.

Antibiotic prescribing trends in primary care 2014–2022

Antimicrobial resistance (AMR) is a global healthcare challenge that governments and health systems are tackling primarily through antimicrobial stewardship (AMS). This should, improve antibiotic use, avoid inappropriate prescribing, reduce prescription numbers, aligning with national/international AMS targets. In primary care in the United Kingdom (UK) antibiotics are mainly prescribed for patients with urinary and respiratory symptoms (22.7% and 46% of all antibiotic prescriptions respectively).This study aimed to capture the time-series trends (2014–2022) for commonly prescribed antibiotics for respiratory and urinary tract infections in primary care in England. Trends for Amoxicillin, Amoxicillin sodium, Trimethoprim, Clarithromycin, Erythromycin, Erythromycin ethylsuccinate, Erythromycin stearate, Doxycycline hyclate, Doxycycline monohydrate and Phenoxymethylpenicillin (Penicillin V) were determined. In doing so providing evidence regarding meeting UK antibiotic prescribing rate objectives (a 15% reduction in human antibiotic use 2019–2024).Time series trend analysis of 62,949,272 antibiotic prescriptions from 6,370 General Practices in England extracted from the National Health Service (NHS) Business Services Authority web portal were explored. With additional investigation of prescribing rate trends by quintiles of the Index of Multiple Deprivation (IMD).Overall, there is a downwards trend in antibiotic prescribing for those explored. There is an association between IMD, geographical location, and higher antibiotic prescribing levels (prescribing hot spots). England has a well-documented North-South divide of health inequalities, this is reflected in antibiotic prescribing. The corona virus pandemic (COVID-19) impacted on AMS, with a rise in doxycycline and trimethoprim prescriptions notable in higher IMD areas. Since then, prescribing appears to have returned to pre-pandemic levels in all IMDs and continued to decline.AMS efforts are being adhered to in primary care in England. This study provides further evidence of the link between locality and poorer health outcomes (reflected in higher antibiotic prescribing). Further work is required to address antibiotic use in hot spot areas.

Erythromycin treatment under a specific nitrogen supply affects carbon metabolism and increases poly(3-hydroxybutyrate) and glycogen accumulation in cyanobacterium Synechocystis sp. PCC 6803

Under an adequate nitrate supply (BG11), cyanobacterium Synechocystis sp. PCC 6803 has high protein content but a low storage of glycogen and poly(3-hydroxybutyrate) (PHB). In contrast, when deprived of nitrogen (N), protein synthesis was repressed and the accumulation of glycogen and PHB was remarkably increased. The repressed protein synthesis caused by sulfur deprivation or treatment with chloramphenicol was also found to slightly enhance PHB accumulation in Synechocystis. Thus, the repressed protein synthesis is associated with the increased PHB and glycogen storage. Here, we examined two other antibiotics that inhibit protein synthesis, erythromycin (EM) and streptomycin (SM) for their effect on the accumulation of PHB and glycogen in Synechocystis. Under N cultivation, 10 μM EM treatment significantly increased the PHB level to 18 % (w/w cell dry weight [DW]) compared to 3 % (w/w DW) in the untreated cells; however, SM treatment did not increase the PHB level. Under BG11 cultivation, exposure to 0.7 μM SM and 5 μM EM enhanced glycogen accumulation up to 15 % and 41 % (w/w DW) respectively, compared to only 7 % (w/w DW) in the untreated cells. The EM treatment also remarkably reduced the total protein and phycobiliprotein contents. Results from metabolomic analysis suggested that EM treatment caused protein degradation into amino acids, some of which were metabolized into substrates that can be used for PHB and glycogen synthesis. This was substantiated by the result showing that EM treated cells had significantly increased levels of both the PHB-synthesizing substrates (acetyl-CoA, acetoacetyl-CoA, and 3-hydroxybutyryl-CoA) when cultured under N, and the glycogen-synthesizing substrates (fructose-1,6-BP, fructose-6-P, glucose-6-P, glucose-1-P, and ADP-glucose) when cultured in BG11. Therefore, EM treatment might be applicable for enhancing the accumulation of these two biopolymers in other cyanobacteria.

The first 5 years of Helicobacter pylori research-With an emphasis on the United Kingdom.

In the 1970s, 1% of the UK population consulted with dyspepsia; fiberoptic gastroscopy allowed biopsy specimens under direct vision enabling systematic histopathology. Steer et al described clusters of flagellated bacteria closely apposed to the gastric epithelium associated with chronic active gastritis. The first UK series of Helicobacter pylori following Marshall's 1983 visit to Worcester confirmed the association of H. pylori with gastritis. UK researchers completed much early helicobacter research as there were many UK campylobacteriologists. Steer and Newell proved the Campylobacter-like organisms grown on culture were the same as those seen in the gastric mucosa using antiserum raised by inoculating rabbits with H. pylori from cultures. Wyatt, Rathbone, and others showed a strong correlation between the number of organisms, type and severity of acute gastritis, immunological response, and bacterial adhesion similar to enteropathogenic E coli. Seroprevalence studies indicated H. pylori increased with age. Histopathologists also showed peptic duodenitis was in effect "gastritis in the duodenum" caused by H. pylori, unifying its role in the pathogenesis of both gastritis and duodenal ulceration. These bacteria were initially called Campylobacter pyloridis and then C. pylori. However, electron microscopy suggested that the bacteria were not campylobacters, and this was supported by differences in fatty acid and polyacrylamide electrophoresis profiles. In-vitro tests indicated that H. pylori was susceptible to penicillins, erythromycin, and quinolones, but not trimethoprim or cefsulodin allowing development of selective media for culture. Monotherapy with erythromycin ethylsuccinate was ineffective, and patients treated with bismuth subsalicylate initially responded with clearance of H. pylori and the associated gastritis, but then many relapsed. Thus, pharmacokinetic and treatment studies were important to direct suitable dual and triple treatments. Work optimized serology, and the rapid biopsy urease and urea breath tests. The link between H.pylori and gastric cancer was established in large seroprevalence studies, and H. pylori test and treat for dyspepsia became routine.

Co-Application of Sewage Sludge, Chinese Medicinal Herbal Residue and Biochar Attenuated Accumulation and Translocation of Antibiotics in Soils and Crops

Sewage sludge (SL), Chinese medicinal herbal residues (CMHRs) and the raw materials of biochar (BC) are normally treated as wastes. However, SL, CMHRs and BC are potential candidates for soil amendments. The performances of soils amended with three different proportions (5%, 10% and 20% on a dry-weight basis) of SL-BC and SL-CMHR-BC in terms of ameliorating soil properties and attenuating antibiotics in soil–plant systems were investigated with two common crop species: carrot and lettuce. The amended soils in general showed higher nutrient levels than the control soils, and particularly for the 20% SL-CMHR-BC. The soils with 10% or 20% SL-BC or SL-CMHR-BC apparently retarded the germination performances of the two crop species, but the negative effects were not noticeable after a growing period. Six target antibiotics, amoxicillin (AMX), tetracycline (TC), sulfamethazine (SMX), norfloxacin (NOR), erythromycin (ERY) and chloramphenicol (CAP), were applied for growing the crops by using irrigation water with 3 μg L−1 (IW3) and 30 μg L−1 (IW30) of each antibiotic. The amended soils led to lower levels of antibiotics in the soils and crop tissues as compared with the control, with the 20% SL-CMHR-BC soils showing the most pronounced effect. The effects of the soil amendments on the bioconcentration factor (BCF) varied, but generally with lower values in the amended soils. Both SL-BC and SL-CMHR-BC were proven in the study as potential soil amendments for alleviating the environmental dispersal and human exposure risks of different antibiotics, and specifically 20% SL-CMHR-BC.

Combined toxicity of erythromycin and roxithromycin and their removal by Chlorella pyrenoidosa

The ecological effects of antibiotics in surface water have attracted increasing research attention. In this study, we investigated the combined ecotoxicity of erythromycin (ERY) and roxithromycin (ROX) on the microalgae, Chlorella pyrenoidosa, and the removal of ERY and ROX during the exposure. The calculated 96-h median effect concentration (EC50) values of ERY, ROX, and their mixture (2:1 w/w) were 7.37, 3.54, and 7.91 mg∙L-1, respectively. However, the predicted EC50 values of ERY+ROX mixture were 5.42 and 1.51 mg∙L-1, based on the concentration addition and independent action models, respectively. This demonstrated the combined toxicity of ERY+ ROX mixture showed an antagonistic effect on Chlorella pyrenoidosa. During the 14-d culture, low-concentration (EC10) treatments with ERY, ROX, and their mixture caused the growth inhibition rate to decrease during the first 12 d and increase slightly at 14 d. In contrast, high-concentration (EC50) treatments significantly inhibited microalgae growth (p < 0.05). Changes in the total chlorophyll contents, SOD and CAT activities, and MDA contents of microalgae suggested that individual treatments with ERY and ROX induced higher oxidative stress than combined treatments. After the 14-d culture time, residual Ery in low and high concentration Ery treatments were 17.75% and 74.43%, and the residual Rox were 76.54% and 87.99%, but the residuals were 8.03% and 73.53% in ERY+ ROX combined treatment. These indicated that antibiotic removal efficiency was higher in combined treatments than that in individual treatments, especially at low concentrations (EC10). Correlation analysis suggested that there was a significant negative correlation between the antibiotic removal efficiency of C. pyrenoidosa and their SOD activity and MDA content, and the enhanced antibiotic removal ability of microalgae benefited from increased cell growth and chlorophyll content. Findings in this study contribute to predicting ecological risk of coexisting antibiotics in aquatic environment, and to improving biological treatment technology of antibiotics in wastewater.

Molecular dynamics simulations on interactions of five antibiotics with luciferase of Vibrio Qinghaiensis sp.-Q67

A large number of antibiotics have been used in the medical industry, agriculture, and animal husbandry industry in recent years. It may cause pollution to the aquatic environment and ultimately threaten to human health due to their prolonged exposure to the environment. We aim to study the toxicity mechanism of enrofloxacin (ENR), chlortetracycline hydrochloride (CTC), trimethoprim (TMP), chloramphenicol (CMP), and erythromycin (ETM) to luciferase of Vibrio Qinghaiensis sp.-Q67 (Q67) by using toxicity testing combined with molecular docking, molecular dynamics, and binding free energy analysis. The curve categories for ENR were different from the other four antibiotics, with ENR being J-type and the rest being S-type, and the toxicity of these five antibiotics (pEC50) followed the order of ENR (7.281) > ETM (6.814) > CMP (6.672) > CTC (6.400) > TMP (6.123), the order of toxicity value is consistent with the the magnitude of the binding free energy (ENR (−47.759 kcal/mol), ETM (−46.821 kcal/mol), CMP (−42.905 kcal/mol), CTC (−40.946 kcal/mol), TMP (−28.251 kcal/mol)). The van der Waals force provided the most important contribution to the binding free energy of the five antibiotics in the binding system with Q67 luciferase. Therefore, the dominant factor for the binding of antibiotics to luciferase was shape compensation. The face-to-face π-π stacking interaction between the diazohexane structure outside the active pocket region and the indoles structure of Phe194 and Phe250 in the molecular structure was the main reason for the highest toxicity value of antibiotic ENR. The hormesis effect of ENR has a competitive binding relationship with the α and β subunits of luciferase. Homology modeling, molecular docking, molecular dynamics simulations and binding free energy calculations were used to derive the toxicity magnitude of different antibiotics against Q67, and insights at the molecular level. The conclusion of toxicological experiments verified the correctness of the simulation results. This study contributes to the understanding of toxicity mechanisms of five antibiotics and facilitates risk assessment of antibiotic contaminants in the aquatic environment.

ERYTHROMYCIN-DOPED NANOFIBRE COATING ENHANCES OSSEOINTEGRATION AND INHIBITS STAPHYLOCOCCUS AUREUS-INDUCED OSTEOLYSIS

Failure of osseointegration and periprosthetic joint infection (PJI) are the two main reasons of implant failure after total joint replacement (TJR). Nanofiber (NF) implant surface coating represents an alternative local drug eluting device that improves osseointegration and decreases the risk of PJI. The purpose of this study was to investigate the therapeutic efficacies of erythromycin (EM)-loaded coaxial PLGA/PCL-PVA NF coating in a rat S. aureus-infected tibia model.NF coatings with 100mg and 1000mg EM were prepared. NF without EM was included as positive control. 56 Sprague Dawley rats were divided into 4 groups. A titanium pin (1.0-mm x 8 mm) was placed into the tibia through the intercondylar notch. S. aureus (SA) was introduced by both direct injection of 10 μl broth (1 × 104 CFU) into the medullary cavity and single dip of Ti pins into a similar solution prior to insertion. Rats were sacrificed at 8 and 16 weeks after surgery. The outcome measurements include μCT based quantitative osteolysis evaluation and hard tissue histology.Results: EM-NF coating (EM100 and EM1000) reduced osteolysis at 8 and 16 weeks, compared to EM0 and negative control. The effective infection control by EM-NFs was further confirmed by hard tissue section analysis. The Bone implant contact (BIC) and bone area fraction Occupancy (BAFO) within 200 µm of the surface of the pins were used to evaluate the osseointegration and new bone formation around the implants. At 16 weeks, the bone implant contact (BIC) of EM 100 (35.08%) was higher than that of negative control (3.43%) and EM0 (0%). The bone area fraction occupancy within 200 µm (BAFO) of EM100 (0.63 mm2) was higher than that of negative control (0.390 mm2) and EM0 (0.0 mm2). The BAFO of EM100 was also higher than that of EM1000 (0.3mm2).There was much less osteolysis observed with EM100 and EM1000 NF coatings at 16 weeks, as compared to EM0 positive control, p=0.08 and p=0.1, respectively. Osseointegration and periprosthetic bone formation was enhanced by EM-NFs, especially EM100. Data from this pilot study is promising for improving implant surface fabrication strategies.

A Robust Homogeneous Fluorescence Polarization Immunoassay for Rapid Determination of Erythromycin in Milk.

Erythromycin (ERY) is one of the most common macrolides applied in veterinary medicine to treat diseases or as a feed additive for animal growth promotion. Long-term irrational use of ERY could lead to residues in animal-derived food and the emergence of drug-resistant strains, posing potential threats to human health. In this study, a highly sensitive, specific, robust, and rapid fluorescence polarization immunoassay (FPIA) for the determination of ERY in milk has been described. Herein, to achieve high sensitivity, five tracers of ERY with different fluorescein structures were synthesized and paired with three monoclonal antibodies (mAbs). Under the optimized conditions, the combination of mAb 5B2 and tracer ERM-FITC achieved the lowest IC50 value in the FPIA with 7.39 μg/L for ERM. The established FPIA was used to detect ERY in milk, revealing a limit of detection (LOD) of 14.08 μg/L with recoveries of 96.08-107.77% and coefficients of variations (CVs) of 3.41-10.97%. The total detection time of the developed FPIA was less than 5 min from the addition of samples to the result readout. All the above results showed that the proposed FPIA in this study was a rapid, accurate, and simple method for the screening of ERY in milk samples.

Membrane fouling mechanism of submerged membrane bioreactor during erythromycin removal

Background: Based on the previous studies, antibiotics can have affected biological properties of biomass and fouling properties of mixed liquor in aeration tank. The present study was conducted to explore the fouling mechanisms of membrane bioreactor (MBR) system during the treatment of wastewater containing erythromycin (ERY) antibiotic under several mixed liquor suspended solids (MLSS) concentrations. Methods: A lab-scale two-chamber MBR system equipped with a polypropylene hollow fiber submerged membrane was fed with synthetic wastewater containing different initial concentrations of ERY. MBR system was operated under the constant flux mode and different MLSS concentrations (5.0-13.0 g/L) and the obtained results were evaluated using different individual and combined fouling models. Results: The variation of MLSS concentrations had not significantly affected the kind of best-fitted model. From the individual models, the standard model indicated the best performance for permeate prediction under different MLSS concentrations (R2 adj&gt;0.997). For all studied MLSS concentrations, the R2 adj values of combined fouling models were higher than 0.986 and demonstrated good fitness performance of combined models compared to individual models. Overall, the cake-intermediate model showed the lowest fitness, and cake-complete and complete-standard models were the most successful models in filtrated volume prediction in comparison with other combined fouling models. Conclusion: This study indicated that mechanistic models are suitable for fouling prediction of MBR systems in ERY removal and under a wide range of MLSS concentrations and provide valuable information on fouling mechanisms of full-scale MBR systems.

Ultraversatile Fluorescent Sensors Based on Two CoII/NiII Coordination Polymers for Identifying Various Antibiotics via the Turn-On/Off Effect and Detecting pH

Because the accurate and rapid detection of antibiotics and pH plays an important role in biological systems and environmental fields, developing suitable and efficient sensors that can simultaneously detect antibiotics and pH has become important. In this work, we successfully designed and synthesized two new one-dimensional coordination polymers based on the mixed ligands L [N,N'-bis(4-methylpyridin-4-yl)-2,6-naphthalene dicarboxylamide] and H2CPG [3-(4-chlorophenyl)glutaric acid], [M(L)(HCPG)2(H2O)2] (M = Co for CP 1, and M = Ni for CP 2), which were structurally characterized by single-crystal X-ray diffraction, infrared spectroscopy, powder X-ray diffraction, and thermogravimetric analysis. CP 1 and CP 2 can be used as ultraversatile fluorescent sensors, which can sense erythromycin (ERY) and oxacillin (OXC) by turn-on fluorescent enhancement and detect furaltadone (FTD) via the turn-off fluorescent quenching effect, separately. The concentration ranges of different analytes sensed by CPs 1 and 2 were 0-0.046 and 0-0.069 mM for ERY, 0-0.04 and 0-0.028 mM for OXC, and 0-0.155 and 0-0.019 mM for FTD, respectively. Moreover, CP 2 can effectively sense pH, in both a wide pH range and the fine physiological range. The sensors have a rapid luminescence response, good recyclability, and excellent fluorescence stability. More importantly, they not only represent the first example of detecting ERY or OXC based on fluorescent CPs but also are the very rare ultraversatile fluorescent sensors. The fluorescent sensing mechanism for antibiotics and pH was discussed in detail.

TLC densitometric analysis of triple antibiotic therapy; Erythromycin, Sulfadiazine and Trimethoprim in different edible chicken tissues

Erythromycin (ERY) is one of the macrolides used abundantly in veterinary medicines to treat various infections including respiratory, skin and bones. Combination of sulfadiazine (SFD) and trimethoprim (TMP) has proven efficacy and is widely used in the treatment of many infectious diseases, due to the efficiency of SFD as a bactericidal and TMP as a bacteriostatic. On the other hand, those residues of antibiotics like ERY, SFD and TMP in animal tissues may pose health hazards to humans. A simple and cost effective TLC densitometeric method has been developed to analyze the above mentioned drugs in their dosage form and in spiked chicken muscle and liver samples. A mixture of chloroform: methanol: ammonia hydroxide solution (33%, v/v) (8.5:1.5:0.1, by volume) was the developing system. In order to obtain the highest possible sensitivity, the separated bands were exposed to iodine vapors in well closed container for 15 min and then detection was immediately done at 220 nm. Linearity was achieved in the ranges of 0.5–10, 0.1–2 µg/band for ERY and SFD, respectively in both spiked muscle and liver samples while for TMP, linearity was proved over the ranges of 0.1–1.8 µg/band for spiked muscle samples and 0.1–1.6 for spiked liver samples.

Antibiotic pollution of the Yellow River in China and its relationship with dissolved organic matter: Distribution and Source identification

Understanding the sources of antibiotics is important for managing antibiotic contamination and preventing environmental risks in the aquatic environment. In this study, the distribution of dissolved organic matter (DOM) and 24 antibiotics from four typical classes (quinolones, macrolides, sulfonamides and tetracyclines) in the Yellow River basin containing distinct sources of pollution was investigated. In particular, relationships between the antibiotic concentrations and fluorescent properties of DOM were to be established to identify antibiotic sources. A total of 22 antibiotics were detected, with maximum concentrations ranging from 0.27 to 30.14 ng/L in the mainstream of the Yellow River. Of these antibiotics, only erythromycin (ERY) and sulfamethoxazole (SMX) posed potential risks to aquatic organisms. Spatially, tetracyclines were mainly distributed in the upstream reaches of the river, and quinolones were largely distributed in the midstream. High levels of sulfonamides were present downstream of the investigated river. Only EYR belonging to the macrolide group was detected and had a high downstream concentration. EEM-PARAFAC analysis showed that DOM was composed of visible fulvic acid-like fluorescence fraction (C1), ultraviolet fulvic acid-like fluorescence fraction (C2) and protein-like fraction (C3). Using Pearson correlation analysis, this study demonstrated a close relationship between DOM spectral parameters and antibiotic concentrations in the Yellow River basin. Specifically, r (C3, C2) was significantly and positively correlated with the concentrations of SMX, sulfadoxine (SDX), and ERY, while humification index (HIX) had an opposite relationship with these antibiotics. These results suggested that SMX, SDX and ERY were mainly discharged from wastewater treatment plants into the mainstream of the Yellow River. This work provides a powerful demonstration that DOM plays an important role in indicating the occurrence and sources of antibiotics in the aquatic environment.

A new insight into the potential drivers of antibiotic resistance gene enrichment in the collembolan gut association with antibiotic and non-antibiotic agents

Effects of non-antibiotic pharmaceuticals on antibiotic resistance genes (ARGs) in soil ecosystem are still unclear. In this study, we explored the microbial community and ARGs variations in the gut of the model soil collembolan Folsomia candida following soil antiepileptic drug carbamazepine (CBZ) contamination, while comparing with antibiotic erythromycin (ETM) exposure. Results showed that, CBZ and ETM all significantly influenced ARGs diversity and composition in the soil and collembolan gut, increasing the relative abundance of ARGs. However, unlike ETM, which influences ARGs via bacterial communities, exposure to CBZ may have primarily facilitated enrichment of ARGs in gut through mobile genetic elements (MGEs). Although soil CBZ contamination did not pose an effect on the gut fungal community of collembolans, it increased the relative abundance of animal fungal pathogens contained therein. Soil ETM and CBZ exposure both significantly increased the relative abundance of Gammaproteobacteria in the collembolan gut, which may be used to indicate soil contamination. Together, our results provide a fresh perspective for the potential drivers of non-antibiotic drugs on ARG changes based on the actual soil environment, revealing the potential ecological risk of CBZ on soil ecosystems involving ARGs dissemination and pathogens enrichment.

Erythromycin Restores Osteoblast Differentiation and Osteogenesis Suppressed by Porphyromonas gingivalis Lipopolysaccharide.

The macrolide erythromycin (ERM) inhibits excessive neutrophil accumulation and bone resorption in inflammatory tissues. We previously reported that the expression of developmental endothelial locus-1 (DEL-1), an endogenous anti-inflammatory factor induced by ERM, is involved in ERM action. Furthermore, DEL-1 is involved in the induction of bone regeneration. Therefore, in this study, we investigated whether ERM exerts an osteoblastogenic effect by upregulating DEL-1 under inflammatory conditions. We performed in vitro cell-based mechanistic analyses and used a model of Porphyromonas gingivalis lipopolysaccharide (LPS)-induced periodontitis to evaluate how ERM restores osteoblast activity. In vitro, P. gingivalis LPS stimulation suppressed osteoblast differentiation and bone formation. However, ERM treatment combined with P. gingivalis LPS stimulation upregulated osteoblast differentiation-related factors and Del1, indicating that osteoblast differentiation was restored. Alveolar bone resorption and gene expression were evaluated in a periodontitis model, and the results confirmed that ERM treatment increased DEL-1 expression and suppressed bone loss by increasing the expression of osteoblast-associated factors. In conclusion, ERM restores bone metabolism homeostasis in inflammatory environments possibly via the induction of DEL-1.

Commonly Used Therapeutics Associated with Changes in Arousal Inhibit GABAAR Activation.

GABAA receptor-positive modulators are well-known to induce sedation, sleep, and general anesthesia. Conversely, GABAA receptor negative allosteric modulators (GABAARNAMs) can increase arousal and induce seizures. Motivated by our studies with patients with hypersomnia, and our discovery that two GABAARNAMs can restore the Excitation/Inhibition (E/I) balance in vitro and arousal in vivo, we chose to screen 11 compounds that have been reported to modulate arousal, to see if they shared a GABA-related mechanism. We determined modulation with both conventional and microfluidic patch clamp methods. We found that receptor activation was variably modulated by all 11 compounds: Rifampicin (RIF), Metronidazole (MET), Minocycline (MIN), Erythromycin (ERY), Ofloxacin (OFX), Chloroquine (CQ), Hydroxychloroquine sulfate (HCQ), Flumazenil (FLZ), Pentylenetetrazol (PTZ), (-)-Epigallocatechin Gallate (EGCG), and clarithromycin (CLR). The computational modeling of modulator-receptor interactions predicted drug action at canonical binding sites and novel orphan sites on the receptor. Our findings suggest that multiple avenues of investigation are now open to investigate large and brain-penetrant molecules for the treatment of patients with diminished CNS E/I balance.

Preparation of composite nanofiltration membrane with interlayer for pharmaceutical rejection

It is necessary to prepare a nanofiltration (NF) membrane with high water permeability and excellent pharmaceutical selectivity. In this study, polydopamine/poly(sulfobetaine methacrylate) (PDA/PSBMA) was selected as the interlayer to improve the water permeance of polyamide (PA) composite NF membrane. The introduction of the PDA/PSBMA interlayer led to an increase in the degree of crosslinking of the PA layer and the formation of cracks inside and below the PA layer. As a result, a negatively charged NF membrane with a molecular weight cut-off (MWCO) of 348 Da and an average pore size of 0.23 nm was obtained. The pure water permeance of the optimal NF membrane was 22.0 L·m−2·h−1·bar−1, and the Na2SO4 rejection was 98.9%. Meanwhile, this NF membrane showed excellent rejection of antibiotics. The rejections of erythromycin (ERY), tetracycline hydrochloride (TC), and cephalexin (CA) were 100.0%, 99.4%, and 97.5%, respectively. The separation coefficients of NaCl/TC and NaCl/ERY were as high as 108.2 and 80.8, respectively. In addition, this NF membrane demonstrated outstanding properties in terms of antifouling and long-term stability. The NF membrane with PDA/PSBMA interlayer has excellent potential for pharmaceutical wastewater treatment and antibiotic extraction.

Distribution of Multidrug-Resistant Invasive Serotypes of Streptococcus pneumoniae during the Period 2007-2021 in Madrid, Spain.

After the systematic use of conjugate vaccines, the invasive pneumococcal disease (IPD) was included into the Madrid Notifiable Diseases Surveillance System through an Epidemiological Surveillance Network. Furthermore, Streptococcus pneumoniae was included in the Spanish Plan of Antibiotic Resistance. The aim of this study was to analyse the multidrug-resistant (MDR) phenotype distribution among invasive strains of Streptococcus pneumoniae isolated during 2007-2021 from usually sterile clinical samples in Madrid, Spain. A total number of 7133 invasive pneumococcal isolates were studied during the period from February 2007 to December 2021. Serotyping was characterised using the Pneumotest-Latex and by the Quellung reaction. Antibiotic susceptibility testing to penicillin (PEN), erythromycin (ERY), and levofloxacin (LVX) was performed using the E-test according to the EUCAST guidelines and breakpoints. Combination of non-susceptibility to PEN at standard dosing regimen (PNSSDR), resistance to ERY (ERYR) and to LVX (LVXR) was considered to be multidrug-resistant at standard dosing regimen of penicillin (MRPSDR), whereas the combination of resistance to PEN (PENR), ERYR, and LVXR was considered multidrug-resistant (MDR). The number of MDRPSDR and or MDR strains in the entire population (n = 7133) during the complete period (2007-2021) were 51 (0.7%) and 6 (0.1%), respectively. All MDRPSDR and/or MDR strains belonged to nine serotypes: 19A (n = 13), 15A (n = 12), 9V (n = 12), 14 (n = 7), 24F (n = 3), 15F (n = 1), 19F (n = 1), 6B (n = 1) and 6C (n = 1). Only two serotypes (9V and 19A) were found among MDR strains, and most of them (5/6) belonged to serotype 9V. Only 12.4% of the strains typified as serotype 9V were MDRPSDR and only 5.2% as MDR. The levels of pneumococcal MDRPSDR and/or MDR in this study were low and all six MDR strains were isolated between 2014 and 2018. These results reinforce the importance of monitoring the evolution of non-susceptible serotypes including those with MDR in the coming years, especially after the introduction of new conjugate vaccines of a broader spectrum.

Prediction of pharmaceuticals removal in activated sludge system under different operational parameters using an extended ASM-PhACs model

Removal of pharmaceuticals is essential in wastewater treatment systems due to their release and accumulation in the environment, which are raising issues for the environment and human health. A mathematical model could be used to predict pharmaceuticals removal under various operational parameters and assess the contributions of different removal pathways to pharmaceuticals removal. Here an ASM-PhACs model was established to describe pharmaceuticals removal including diclofenac (DCF), erythromycin (ERY), gemfibrozil (GEM) and carbamazepine (CBZ) removal in activated sludge system. The pharmaceuticals removal processes linked to co-metabolic biodegradation through the growth of ammonia oxidizing bacteria (AOB), metabolic biodegradation through AOB, metabolic biodegradation through heterotrophic bacteria (HB) and sludge adsorption were incorporated into activated sludge model (ASM1) framework. The kinetic equations were established for each pharmaceuticals removal process. To provide the experimental data for model calibration and validation, two sets of batch tests were designed and conducted in the laboratory scale using SBR technology. According to the batch test data and results of sensitivity analysis, the newly added parameters and some original default parameters affecting pharmaceuticals removal processes were screened and calibrated. The model could accurately simulate all the dynamics of chemical oxygen demand, nitrogen and pharmaceuticals under various conditions. To explore the effect of operational parameters on pharmaceuticals removal efficiency, the wide range of operational parameters was analyzed during model simulation. According to the simulation results, both influent NH4+-N concentration and DO were found to be the significant parameters that impact the removal of DCF, ERY and GEM. AOB biodegradation played an important role in DCF, ERY and GEM removal. The developed model framework helps to investigate the removal mechanisms and key influencing factors of pharmaceuticals removal, thus providing guidelines for reactor design, operation and optimization aiming at pharmaceuticals removal.