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ADMET & DMPK 2020The bioavailability of tetracyclines is markedly decreased when co-administered with antacids, milk, or food containing Ca. Previously, it was suggested that the...
The bioavailability of tetracyclines is markedly decreased when co-administered with antacids, milk, or food containing Ca. Previously, it was suggested that the effective intestinal permeation of tetracycline (TC) was decreased due to Ca linked mucin binding in the mucosal side. In the present study, we investigated the effect of Ca, Mg, and mucin on the membrane permeation of six tetracyclines (TC, oxytetracycline (OTC), minocycline (MINO), doxycycline (DOXY), demeclocycline (DMCTC), and chlortetracycline (CTC)). The membrane permeability values (P) of tetracyclines were measured by the parallel artificial membrane permeation assay (PAMPA) using soybean lecithin - decane (SL-PAMPA) and octanol (OCT-PAMPA) membranes. In SL-PAMPA, Ca markedly decreased the P values of all tetracyclines. In OCT-PAMPA, Ca increased the P values of TC, CTC, and DMCTC, but not DOXY, OTC, and MINO. Mg decreased the P values of all tetracyclines in both SL-PAMPA and OCT-PAMPA (except for CTC in OCT-PAMPA). The addition of mucin had little or no effect in all cases. In contrast to the previously suggested mechanism, the results of the present study suggested that Ca chelate formation decreased the membrane permeation of tetracyclines, irrespective of Ca linked mucin binding. Molecular speciation analysis suggested that the permeation of TC - metal chelates was negligibly small in SL-PAMPA.
PubMed: 35300369
DOI: 10.5599/admet.797 -
Frontiers in Immunology 2020Myeloid cells that infiltrate into brain tumors are deactivated or exploited by the tumor cells. We previously demonstrated that compromised microglia, monocytes, and...
Myeloid cells that infiltrate into brain tumors are deactivated or exploited by the tumor cells. We previously demonstrated that compromised microglia, monocytes, and macrophages in malignant gliomas could be reactivated by amphotericin-B to contain the growth of brain tumorinitiating cells (BTICs). We identified meclocycline as another activator of microglia, so we sought to test whether its better-tolerated derivative, demeclocycline, also stimulates monocytes to restrict BTIC growth. Monocytes were selected for study as they would be exposed to demeclocycline in the circulation prior to entry into brain tumors to become macrophages. We found that demeclocycline increased the activity of monocytes in culture, as determined by tumor necrosis factor-α production and chemotactic capacity. The conditioned medium of demeclocycline-stimulated monocytes attenuated the growth of BTICs generated from human glioblastoma resections, as evaluated using neurosphere and alamarBlue assays, and cell counts. Demeclocycline also had direct effects in reducing BTIC growth. A global gene expression screen identified several genes, such as DNA damage inducible transcript 4, frizzled class receptor 5 and reactive oxygen species modulator 1, as potential regulators of demeclocycline-mediated BTIC growth reduction. Amongst several tetracycline derivatives, only demeclocycline directly reduced BTIC growth. In summary, we have identified demeclocycline as a novel inhibitor of the growth of BTICs, through direct effect and through indirect stimulation of monocytes. Demeclocycline is a candidate to reactivate compromised immune cells to improve the prognosis of patients with gliomas.
Topics: Antineoplastic Agents; Brain Neoplasms; Carcinogenesis; Cell Growth Processes; Cells, Cultured; Demeclocycline; Glioma; Humans; Monocytes; Neoplastic Stem Cells; Tumor-Associated Macrophages
PubMed: 32153581
DOI: 10.3389/fimmu.2020.00272 -
Cureus Dec 2019Syndrome of inappropriate antidiuretic hormone secretion may be a frequent accompaniment of aging without an obvious central nervous system or pulmonary disorder, tumor,...
Syndrome of inappropriate antidiuretic hormone secretion may be a frequent accompaniment of aging without an obvious central nervous system or pulmonary disorder, tumor, or drugs as the confounding factor. Treatment is often warranted due to complex symptomatology that is often associated with unfavorable clinical outcomes. Although V-receptor antagonists are effective in increasing serum sodium, their side-effect profile and cost may be a barrier to its use. We report a patient with symptomatic, severe, chronic hyponatremia requiring multiple hospitalizations, who was successfully maintained on long-term demeclocycline therapy.
PubMed: 31988816
DOI: 10.7759/cureus.6415 -
Future Medicinal Chemistry Sep 2019Tetracyclines are well established antibiotics but show phototoxicity as a side effect. Antimicrobial photodynamic inactivation uses nontoxic dyes combined with harmless... (Review)
Review
Tetracyclines are well established antibiotics but show phototoxicity as a side effect. Antimicrobial photodynamic inactivation uses nontoxic dyes combined with harmless light to destroy microbial cells by reactive oxygen species. Tetracyclines (demeclocycline and doxycycline) can act as light-activated antibiotics by binding to bacterial cells and killing them only upon illumination. The remaining tetracyclines can prevent bacterial regrowth after illumination has ceased. Antimicrobial photodynamic inactivation can be potentiated by potassium iodide. Azide quenched the formation of iodine, but not hydrogen peroxide. Demeclotetracycline (but not doxycycline) iodinated tyrosine after light activation in the presence of potassium iodide. Bacteria are killed by photoactivation of tetracyclines in the absence of oxygen. Since topical tetracyclines are already used clinically, blue light activation may increase the bactericidal effect.
Topics: Anti-Bacterial Agents; Bacteria; Light; Photochemotherapy; Photosensitizing Agents; Tetracyclines
PubMed: 31544504
DOI: 10.4155/fmc-2018-0513 -
JBMR Plus Jul 2019Hypercalcemia most often results from primary hyperparathyroidism and malignancy. Adynamic bone disease (ABD) is a form of renal osteodystrophy characterized by reduced...
Hypercalcemia most often results from primary hyperparathyroidism and malignancy. Adynamic bone disease (ABD) is a form of renal osteodystrophy characterized by reduced bone turnover, which can limit the ability of bone to release or store calcium, potentially leading to low, normal, or high serum calcium levels. We describe a 51-year-old dialysis-dependent female with hypercalcemia after parathyroidectomy. A demeclocycline-labeled bone biopsy confirmed adynamic bone disease. Teriparatide, a recombinant form of parathyroid hormone (PTH) used to treat postmenopausal osteoporosis, was prescribed for 12 months and normalized serum calcium levels. Although previous case reports and series have described favorable changes in spine bone mineral density when teriparatide was prescribed for ABD, ours is the first documented case in which teriparatide resolved hypercalcemia due to ABD. © 2019 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
PubMed: 31372586
DOI: 10.1002/jbm4.10176 -
Cureus Jan 2019The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is defined as hyponatremia with inappropriately concentrated urine in a euvolemic patient....
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is defined as hyponatremia with inappropriately concentrated urine in a euvolemic patient. SIADH is associated with a wide spectrum of clinical conditions. In the hospital, hyponatremia carries significant mortality with a prolonged duration of inpatient stay. It is imperative that the underlying cause is appropriately investigated and such patients are closely monitored. This article presents a case of difficult-to-treat hyponatremia secondary to SIADH in a patient with a rare isolated central nervous system (CNS) relapse from a non-Hodgkin's lymphoma (NHL). A relapse, particularly affecting the CNS, carries a poor prognosis. The patient was started on dexamethasone and offered treatment with methotrexate but declined. The hyponatremia failed to respond to fluid restriction and demeclocycline. The hyponatremia responded to a single dose of tolvaptan. Clinicians should have a low index of suspicion for a relapse of lymphoma as a cause of difficult to treat hyponatremia in any patient who has previously had remission from lymphoma treatment.
PubMed: 30931179
DOI: 10.7759/cureus.3905 -
The Cochrane Database of Systematic... Feb 2019Traumatic dental injuries are common. One of the most severe injuries is when a permanent tooth is knocked completely out of the mouth (avulsed). In most circumstances... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Traumatic dental injuries are common. One of the most severe injuries is when a permanent tooth is knocked completely out of the mouth (avulsed). In most circumstances the tooth should be replanted as quickly as possible. There is uncertainty on which interventions will maximise the survival and repair of the replanted tooth. This is an update of a Cochrane Review first published in 2010.
OBJECTIVES
To compare the effects of a range of interventions for managing traumatised permanent front teeth with avulsion injuries.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 8 March 2018), Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2) in the Cochrane Library (searched 8 March 2018), MEDLINE Ovid (1946 to 8 March 2018), and Embase Ovid (1980 to 8 March 2018). The US National Institutes of Health Ongoing Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
We considered randomised and quasi-randomised controlled trials that included a minimum follow-up period of 12 months, for interventions for avulsed and replanted permanent front teeth.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, extracted data and assessed the risk of bias. Authors were contacted where further information about their study was required.
MAIN RESULTS
Four studies, involving a total of 183 participants and 257 teeth were identified. Each of the interventions aimed to reduce infection or alter the inflammatory response or both at the time of or shortly after the tooth or teeth were replanted. Each study assessed a different intervention and therefore it was not appropriate or possible to numerically synthesise the data. All evidence was rated as being of very low quality due to problems with risk of bias and imprecision of results. This means that we are very uncertain about all of the results presented in this review.One study at high risk of bias with 69 participants (138 teeth) compared a 20-minute soak with gentamycin sulphate for both groups prior to replantation with the experimental group receiving daily hyperbaric oxygen for 80 minutes for the first 10 days. There was some evidence of a benefit for the hyperbaric oxygen group in respect of periodontal healing, tooth survival, and pulpal healing.One study at unclear risk of bias with 22 participants (27 teeth) compared the use of two root canal medicaments, Ledermix and Ultracal. There was insufficient evidence of a difference for periodontal healing or tooth survival. This was the only study to formally report adverse events with none identified. Study authors reported that Ledermix caused a greater level of patient dissatisfaction with the colour of avulsed and replanted teeth.A third study at high risk of bias with 19 participants compared extra- or intra-oral endodontics for avulsed teeth which were stored dry for longer than 60 minutes before replantation. There was insufficient evidence of a difference in periodontal healing.The fourth study at high risk of bias with 73 participants compared a 10-minute soak in either thymosin alpha 1 or saline before replantation followed by daily gingival injections with these same medicaments for the first 7 days. There was some evidence of a benefit for thymosin alpha 1 with respect to periodontal healing and tooth survival.
AUTHORS' CONCLUSIONS
Based on the results of the included studies, there is insufficient evidence to support or refute the effectiveness of different interventions for avulsed and replanted permanent front teeth. The overall quality of existing evidence was very low, and therefore great caution should be exercised when generalising the results of the included trials. There is urgent need for further well-designed randomised controlled trials.
Topics: Bone Development; Calcium Hydroxide; Demeclocycline; Drug Combinations; Humans; Hyperbaric Oxygenation; Incisor; Periodontal Ligament; Preoperative Care; Randomized Controlled Trials as Topic; Root Canal Irrigants; Tooth Avulsion; Tooth Discoloration; Tooth Replantation; Triamcinolone Acetonide
PubMed: 30720860
DOI: 10.1002/14651858.CD006542.pub3 -
Scientific Reports Nov 2018Tetracyclines (including demeclocycline, DMCT, or doxycycline, DOTC) represent a class of dual-action antibacterial compounds, which can act as antibiotics in the dark,...
Tetracyclines (including demeclocycline, DMCT, or doxycycline, DOTC) represent a class of dual-action antibacterial compounds, which can act as antibiotics in the dark, and also as photosensitizers under illumination with blue or UVA light. It is known that tetracyclines are taken up inside bacterial cells where they bind to ribosomes. In the present study, we investigated the photochemical mechanism: Type 1 (hydroxyl radicals); Type 2 (singlet oxygen); or Type 3 (oxygen independent). Moreover, we asked whether addition of potassium iodide (KI) could potentiate the aPDI activity of tetracyclines. High concentrations of KI (200-400 mM) strongly potentiated (up to 5 logs of extra killing) light-mediated killing of Gram-negative Escherichia coli or Gram-positive MRSA (although the latter was somewhat less susceptible). KI potentiation was still apparent after a washing step showing that the iodide could penetrate the E. coli cells where the tetracycline had bound. When cells were added to the tetracycline + KI mixture after light, killing was observed in the case of E. coli showing formation of free molecular iodine. Addition of azide quenched the formation of iodine but not hydrogen peroxide. DMCT but not DOTC iodinated tyrosine. Both E. coli and MRSA could be killed by tetracyclines plus light in the absence of oxygen and this killing was not quenched by azide. A mouse model of a superficial wound infection caused by bioluminescent E. coli could be treated by topical application of DMCT and blue light and bacterial regrowth did not occur owing to the continued anti biotic activity of the tetracycline.
Topics: Animals; Anti-Bacterial Agents; Drug Synergism; Escherichia coli; Escherichia coli Infections; Hydrogen Peroxide; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred BALB C; Photochemotherapy; Photosensitizing Agents; Potassium Iodide; Singlet Oxygen; Tetracyclines; Tyrosine; Wound Infection
PubMed: 30459451
DOI: 10.1038/s41598-018-35594-y