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Biosensors Dec 2022As an antibody-free sensing membrane for the detection of the antibiotic tetracycline (TC), a liquid PVC membrane doped with the ion-pair tetracycline/θ-shaped anion...
As an antibody-free sensing membrane for the detection of the antibiotic tetracycline (TC), a liquid PVC membrane doped with the ion-pair tetracycline/θ-shaped anion [3,3'-Co(1,2-CBH)] ([-COSAN]) was formulated and deposited on a SWCNT modified gold microelectrode. The chosen transduction technique was electrochemical impedance spectroscopy (EIS). The PVC membrane was composed of: the tetracycline/[-COSAN] ion-pair, a plasticizer. A detection limit of 0.3 pg/L was obtained with this membrane, using bis(2-ethylhexyl) sebacate as a plasticizer. The sensitivity of detection of tetracycline was five times higher than that of oxytetracycline and of terramycin, and 22 times higher than that of demeclocycline. A shelf-life of the prepared sensor was more than six months and was used for detection in spiked honey samples. These results open the way to having continuous monitoring sensors with a high detection capacity, are easy to clean, avoid the use of antibodies, and produce a direct measurement.
Topics: Plasticizers; Tetracycline; Anti-Bacterial Agents; Microelectrodes; Antibodies; Oxytetracycline
PubMed: 36671906
DOI: 10.3390/bios13010071 -
European Endodontic Journal Oct 2022To explore the long-term effects on discolouration by demeclocycline HCl (Ledermix, LED) or doxycycline hyclate (Doxymix, DOX) pastes placed in extracted human teeth...
OBJECTIVE
To explore the long-term effects on discolouration by demeclocycline HCl (Ledermix, LED) or doxycycline hyclate (Doxymix, DOX) pastes placed in extracted human teeth over a 27-month period under different storage conditions.
METHODS
The canals in 38 teeth were prepared carefully, to minimize exposure to contamination from irrigants, then either LED (Lederle Pharmaceuticals, Germany) or DOX (Ozdent, Australia) were placed. Samples were stored in the dark for 3 months followed by daylight for 24 months. The storage conditions varied as follows: Group 1: Open access, dry storage (OD); Group 2: Closed access, dry storage (CD); Group 3: Open access, wet storage (OW); Group 4: Closed access, wet storage (n=4 for each material). Additional teeth were used as controls: Polyethylene glycol only in a closed canal; and saline only irrigation with LED paste in a closed canal. Standardised digital photographs were taken over 27 months and evaluated for changes in luminosity.
RESULTS
Darkening of tooth structure occurred in all LED groups and in the two DOX groups that were stored wet, during exposure to light, with a faster rate with LED. The most rapid staining occurred with LED in moist conditions with an open access cavity. The least staining occurred with DOX in samples stored dry. With prolonged exposure to light, a reversal in staining occurred with DOX at 3 months and LED at 9 months.
CONCLUSION
Staining of tooth structure is influenced by the choice of medicament, and by exposure to moisture and air. Light has a bimodal effect, first driving staining, but later reversing it. This can be explained by different wavelengths of light causing photodegradation and photo-oxidation of tetracyclines and their complexes with tooth mineral.
Topics: Demeclocycline; Doxycycline; Drug Combinations; Humans; Polyethylene Glycols; Root Canal Irrigants; Tetracyclines; Triamcinolone Acetonide
PubMed: 36217644
DOI: 10.14744/eej.2022.07108 -
Journal of Conservative Dentistry : JCD 2022The aim of this study was to investigate the diffusion of triamcinolone and demeclocycline from an endodontic paste when used unmodified, versus when combined in equal...
AIM
The aim of this study was to investigate the diffusion of triamcinolone and demeclocycline from an endodontic paste when used unmodified, versus when combined in equal parts with a calcium hydroxide paste, in terms of diffusion through the dentinal tubules versus through the apical foramen.
METHODOLOGY
Medicaments were placed in endodontically prepared roots that were kept in vials of Milli-Q water. The five experimental groups in the study were (1) control - no medicament, (2) medicament containing triamcinolone and demeclocycline (T&D) and occluded apex, (3) T&D paste and patent apex, (4) T&D + calcium hydroxide (Ca(OH)) occluded apex, and (5) T&D + Ca(OH) and patent apex. The triamcinolone and demeclocycline concentrations were measured with solid-phase extraction and ultra-high performance liquid chromatography-mass spectrometry, after 1, 3, 8, and 24 h, and after 1 week.
RESULTS
Most of the triamcinolone and demeclocycline diffused through the apical foramen, with sparse diffusion through the dentinal tubules. The T&D paste mixed with Ca(OH) in equal amounts showed greater than the expected 50% reduction in the diffusion of triamcinolone and demeclocycline from mass dilution alone (89% and 80%, respectively).
CONCLUSIONS
These results stress the importance of maintaining apical patency, for allowing diffusion of active components of the drugs to target tissues in the periapical environment.
PubMed: 36187869
DOI: 10.4103/jcd.jcd_206_22 -
Cells Sep 2022The antibiotic tetracycline demeclocycline (DMC) was recently reported to rescue α-synuclein (α-Syn) fibril-induced pathology. However, the antimicrobial activity of...
The antibiotic tetracycline demeclocycline (DMC) was recently reported to rescue α-synuclein (α-Syn) fibril-induced pathology. However, the antimicrobial activity of DMC precludes its potential use in long-term neuroprotective treatments. Here, we synthesized a doubly reduced DMC (DDMC) derivative with residual antibiotic activity and improved neuroprotective effects. The molecule was obtained by removal the dimethylamino substituent at position 4 and the reduction of the hydroxyl group at position 12a on ring A of DMC. The modifications strongly diminished its antibiotic activity against Gram-positive and Gram-negative bacteria. Moreover, this compound preserved the low toxicity of DMC in dopaminergic cell lines while improving its ability to interfere with α-Syn amyloid-like aggregation, showing the highest effectiveness of all tetracyclines tested. Likewise, DDMC demonstrated the ability to reduce seeding induced by the exogenous addition of α-Syn preformed fibrils (α-Syn) in biophysical assays and in a SH-SY5Y-α-Syn-tRFP cell model. In addition, DDMC rendered α-Syn less inflammogenic. Our results suggest that DDMC may be a promising drug candidate for hit-to-lead development and preclinical studies in Parkinson's disease and other synucleinopathies.
Topics: Anti-Bacterial Agents; Demeclocycline; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Lead; Neuroblastoma; Neuroprotective Agents; Synucleinopathies
PubMed: 36078167
DOI: 10.3390/cells11172759 -
PloS One 2022Polycystic ovary syndrome (PCOS) is a common endocrine disorder with high incidence. Recently it has been implicated as a significant risk factor for endometrial cancer...
OBJECTIVE
Polycystic ovary syndrome (PCOS) is a common endocrine disorder with high incidence. Recently it has been implicated as a significant risk factor for endometrial cancer (EC). Our study aims to detect shared gene signatures and biological mechanism between PCOS and EC by bioinformatics analysis.
METHODS
Bioinformatics analysis based on GEO database consisted of data integration, network construction and functional enrichment analysis was applied. In addition, the pharmacological methodology and molecular docking was also performed.
RESULTS
Totally 10 hub common genes, MRPL16, MRPL22, MRPS11, RPL26L1, ESR1, JUN, UBE2I, MRPL17, RPL37A, GTF2H3, were considered as shared gene signatures for EC and PCOS. The GO and KEGG pathway analysis of these hub genes showed that "mitochondrial translational elongation", "ribosomal subunit", "structural constituent of ribosome" and "ribosome" were highly correlated. Besides, associated transcription factors (TFs) and miRNAs network were constructed. We identified candidate drug molecules including fenofibrate, cinnarizine, propanil, fenthion, clindamycin, chloramphenicol, demeclocycline, hydrochloride, azacitidine, chrysene and artenimol according to these hub genes. Molecular docking analysis verified a good binding interaction of fenofibrate against available targets (JUN, ESR1, UBE2I).
CONCLUSION
Gene signatures and regulatory biological pathways were identified through bioinformatics analysis. Moreover, the molecular mechanisms of these signatures were explored and potential drug molecules associated with PCOS and EC were screened out.
Topics: Computational Biology; Endometrial Neoplasms; Female; Fenofibrate; Gene Regulatory Networks; Humans; Molecular Docking Simulation; Polycystic Ovary Syndrome
PubMed: 35830453
DOI: 10.1371/journal.pone.0271380 -
Cureus Apr 2022Hyponatraemia is the most common electrolyte abnormality encountered in the inpatient setting and is associated with increased morbidity, mortality, and length of...
Hyponatraemia is the most common electrolyte abnormality encountered in the inpatient setting and is associated with increased morbidity, mortality, and length of hospital stay. Syndrome of inappropriate anti-diuresis (SIAD) remains the most common cause. Hyponatraemia due to SIAD presents various challenges in treatment approaches, including poor concordance (e.g., to fluid restriction), medication intolerance (e.g., demeclocycline), and risk of rapid sodium shifts (e.g., with vaptan therapy). The use of oral sodium chloride (NaCl) tablets is a recognised treatment approach. However, it is not commonly advocated. We present the cases of two elderly patients in whom the temporary use of NaCl tablets, as an adjunct to fluid restriction, led to safe and effective correction of SIAD-related hyponatraemia with resultant reduced length of hospital admission.
PubMed: 35475246
DOI: 10.7759/cureus.24367 -
Biological & Pharmaceutical Bulletin 2022Cancer immunotherapies are powerful therapeutic options for cancer patients. To enhance the therapeutic effects of cancer immunotherapies, we plan to develop novel...
Cancer immunotherapies are powerful therapeutic options for cancer patients. To enhance the therapeutic effects of cancer immunotherapies, we plan to develop novel immunostimulatory drugs for use in combination with cancer immunotherapy. In the present study, we focused on tetracyclines, the effects of which are controversial for immunotherapy. We examined the effects of tetracyclines on human T cells in the peripheral blood of healthy donors and the tumor tissues of non-small cell lung cancer (NSCLC) patients. By using bispecific T-cell engager technology to assess the cytotoxicity of peripheral T cells against tumor cells, we showed that tetracyclines (minocycline, tetracycline, doxycycline, meclocycline, chlortetracycline, and demeclocycline) enhanced T-cell cytotoxicity through granzyme B expression and CD4+ and CD8+ T-cell proliferation. In analyses of the peripheral blood mononuclear cells (PBMCs) and lung tumor-infiltrated cells of NSCLC patients, we found that demeclocycline enhanced T-cell cytotoxicity not only in PBMCs, but also in lung tumor tissues. These results support the further application of tetracyclines to combination cancer immunotherapy.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Leukocytes, Mononuclear; Lung Neoplasms; Minocycline; T-Lymphocytes
PubMed: 35370267
DOI: 10.1248/bpb.b21-00806 -
Drug Testing and Analysis Jul 2022Oxytetracycline is a broad-spectrum antibiotic, which inhibits protein synthesis and is generally used for the treatment of pneumonia, shipping fever, leptospirosis and...
Oxytetracycline is a broad-spectrum antibiotic, which inhibits protein synthesis and is generally used for the treatment of pneumonia, shipping fever, leptospirosis and wound infections in cattle and swine. The present work proposes a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for oxytetracycline quantification in bull plasma, seminal plasma and urine, requiring limited sample treatment before analysis. Extraction with trichloroacetic acid followed by dilution of the supernatant in mobile phase proved to be effective in all three matrices, allowing to rapidly process large batches of samples. Sharp and symmetrical peak shape was obtained using a BEH C18 reversed-phase column in a chromatographic run of just 3.5 min. The mass spectrometer operated in positive electrospray ionization mode and monitored specific transitions for oxytetracycline (461.1 → 425.8) and the internal standard demeclocycline (465.0 → 447.6). The method was validated over concentration ranges suitable for field concentrations of oxytetracycline found in each matrix, showing good linearity during each day of testing (R always >0.99), as also confirmed by analysis of variance (ANOVA) and lack-of-fit tests. Excellent accuracy and precision were demonstrated by calculated bias always within ±15% and CV% below 10% at all quality control (QC) levels in the three matrices. Matrix effect and recovery were investigated for both analytes, which showed consistent and comparable behaviour in each matrix. To our knowledge, this is the first validated approach for mass spectrometric determination of oxytetracycline in seminal plasma and urine. The method was successfully applied to samples collected during a pharmacokinetic study in bulls, allowing to assess the oxytetracycline concentration-time profile in plasma, seminal plasma and urine.
Topics: Animals; Anti-Bacterial Agents; Cattle; Chromatography, High Pressure Liquid; Chromatography, Liquid; Male; Oxytetracycline; Reproducibility of Results; Semen; Spectrometry, Mass, Electrospray Ionization; Swine; Tandem Mass Spectrometry
PubMed: 35195370
DOI: 10.1002/dta.3246 -
Frontiers in Cellular and Infection... 2021Boromycin is a boron-containing macrolide antibiotic produced by with potent activity against certain viruses, Gram-positive bacteria and protozoan parasites. Most...
Boromycin is a boron-containing macrolide antibiotic produced by with potent activity against certain viruses, Gram-positive bacteria and protozoan parasites. Most antimalarial antibiotics affect plasmodial organelles of prokaryotic origin and have a relatively slow onset of action. They are used for malaria prophylaxis and for the treatment of malaria when combined to a fast-acting drug. Despite the success of artemisinin combination therapies, the current gold standard treatment, new alternatives are constantly needed due to the ability of malaria parasites to become resistant to almost all drugs that are in heavy clinical use. antiplasmodial activity screens of tetracyclines (omadacycline, sarecycline, methacycline, demeclocycline, lymecycline, meclocycline), macrolides (oleandomycin, boromycin, josamycin, troleandomycin), and control drugs (chloroquine, clindamycin, doxycycline, minocycline, eravacycline) revealed boromycin as highly potent against and the zoonotic . In contrast to tetracyclines, boromycin rapidly killed asexual stages of both species already at low concentrations (~ 1 nM) including multidrug resistant strains (Dd2, K1, 7G8). In addition, boromycin was active against stage V gametocytes at a low nanomolar range (IC: 8.5 ± 3.6 nM). Assessment of the mode of action excluded the apicoplast as the main target. Although there was an ionophoric activity on potassium channels, the effect was too low to explain the drug´s antiplasmodial activity. Boromycin is a promising antimalarial candidate with activity against multiple life cycle stages of the parasite.
Topics: Animals; Anti-Bacterial Agents; Antimalarials; Borates; Malaria, Falciparum; Plasmodium falciparum
PubMed: 35096650
DOI: 10.3389/fcimb.2021.802294 -
Photodiagnosis and Photodynamic Therapy Mar 2022This study examined the effect of various root canal irrigants and medicaments on dentin fluorescence elicited by 655 nm visible red laser light. To replicate clinical...
This study examined the effect of various root canal irrigants and medicaments on dentin fluorescence elicited by 655 nm visible red laser light. To replicate clinical use, irrigants were applied onto dentin samples for 2 min, while medicaments were applied for 2 weeks. Fluorescence values tracked from baseline across the following to 24 h, starting 5 min after exposure. Sodium hypochlorite, hydrogen peroxide, and articaine local anaesthetic (4% articaine with 1:1000,000 adrenaline) all significantly quenched fluorescence (p < 0.0001), which then returned to baseline levels after 20 min. Conversely, elevated fluorescence readings were recorded after 3% mepivacaine (p < 0.05), 0.2% chlorhexidine (p < 0.01) and chloroform (p <0.05). A 2 week application of Ledermix™ paste containing 3% demeclocycline caused an irreversible increase in fluorescence (p < 0.0001). Other tested endodontic materials (15% EDTA, eucalyptus oil, calcium hydroxide, Odontopaste™ clindamycin paste, and distilled water) had no impact on dentine fluorescence. The influences of endodontic materials on dentin fluorescence need to considered when using fluorescence endpoints to guide the progress of root canal treatment.
Topics: Calcium Hydroxide; Dental Pulp Cavity; Dentin; Fluorescence; Photochemotherapy; Root Canal Irrigants; Sodium Hypochlorite
PubMed: 34838696
DOI: 10.1016/j.pdpdt.2021.102651