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Antioxidants (Basel, Switzerland) Feb 2023Several studies have reported that the tetracycline (TC) class antibiotic doxycycline () is effective against Parkinson's disease (PD) pathomechanisms. The aim of the...
Several studies have reported that the tetracycline (TC) class antibiotic doxycycline () is effective against Parkinson's disease (PD) pathomechanisms. The aim of the present work was three-fold: (i) Establish a model system to better characterize neuroprotection by ; (ii) Compare the rescue effect of to that of other TC antibiotics; (iii) Discover novel neuroprotective TCs having reduced antibiotic activity. For that, we used cultures of mouse midbrain dopamine (DA) neurons and experimental conditions that model iron-mediated oxidative damage, a key mechanism in PD pathobiology. We found that and the other TC antibiotic, demeclocycline (), provided sustained protection to DA neurons enduring iron-mediated insults, whereas chlortetracycline and non-TC class antibiotics did not. Most interestingly, non-antibiotic derivatives of and , i.e., and , respectively, were also robustly protective for DA neurons. Interestingly, , , and remained protective for DA neurons until advanced stages of neurodegeneration, and the rescue effects of TCs were observable regardless of the degree of maturity of midbrain cultures. Live imaging studies with the fluorogenic probes DHR-123 and TMRM revealed that protective TCs operated by preventing intracellular oxidative stress and mitochondrial membrane depolarization, i.e., cellular perturbations occurring in this model system as the ultimate consequence of ferroptosis-mediated lipid peroxidation. If oxidative/mitochondrial insults were generated acutely, , and were no longer neuroprotective, suggesting that these compounds are mostly effective when neuronal damage is chronic and of low-intensity. Overall, our data suggest that TC derivatives, particularly those lacking antibiotic activity, might be of potential therapeutic utility to combat low-level oxidative insults that develop chronically in the course of PD neurodegeneration.
PubMed: 36978822
DOI: 10.3390/antiox12030575 -
Acta Clinica Croatica Jun 2017When taking different drugs, their possible side effects on the skin should be considered, including skin reactions connected to photosensitivity. This photosensitivity... (Review)
Review
When taking different drugs, their possible side effects on the skin should be considered, including skin reactions connected to photosensitivity. This photosensitivity caused by drugs can appear as phototoxic reactions (which occur more often) or photoallergic reactions (which occur less often and include allergic mechanisms). The following drugs stand out as medications with a high photosensitivity potential: nonsteroidal anti-inflammatory drugs (NSAIDs), cardiovascular drugs (such as amiodarone), phenothiazines (especially chlorpromazine), retinoids, antibiotics (sulfonamides, tetracyclines, especially demeclocycline and quinolones), etc. In recent years, photosensitive reactions to newer drugs have appeared, e.g., targeted anticancer therapies such as BRAF kinase inhibitors (vemurafenib, dabrafenib), EGFR inhibitors, VEGFR inhibitors, MEK inhibitors, Bcr-Abl tyrosine kinase inhibitors, etc. In patients taking drugs over a longer period of time (e.g., NSAIDs, cardiovascular drugs, etc.), a particular problem arises when an unrecognized drug-induced photosensitivity on the skin manifests in summer months. When taking patient histories, the physician/dermatovenereologist should bear in mind that any drug the patient is currently taking may be the cause of skin reactions. Therefore, patients who use potentially photosensitive drugs and treatments on a long term basis should be warned of the possibility of these side effects on their skin and advised to avoid direct exposure to sunlight and to use adequate photoprotection. If patients carefully protect themselves from the sun, it is often not necessary to stop treatments that include photosensitive drugs. If such reactions appear, anti-inflammatory and antiallergic therapies should be introduced.
Topics: Dermatitis, Photoallergic; Dermatitis, Phototoxic; Diagnosis, Differential; Drug-Related Side Effects and Adverse Reactions; Humans; Photosensitivity Disorders; Sunlight
PubMed: 29485795
DOI: 10.20471/acc.2017.56.02.11 -
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 -
International Journal of Clinical... Dec 2015Hyponatraemia (HN) is the most common electrolyte balance disorder in clinical practice. Since the 1970s, demeclocycline has been used in some countries to treat chronic... (Review)
Review
AIMS
Hyponatraemia (HN) is the most common electrolyte balance disorder in clinical practice. Since the 1970s, demeclocycline has been used in some countries to treat chronic HN secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH). The precise mechanism of action of demeclocycline is unclear, but has been linked to the induction of nephrogenic diabetes insipidus. Furthermore, the safety profile of demeclocycline is variable with an inconsistent time to onset, and a potential for complications. There has been no systematic evaluation of the use of demeclocycline for the treatment of HN secondary to SIADH to date. A systematic literature review was performed to obtain an insight into the clinical safety and efficacy of demeclocycline for this condition.
METHODS
Embase(™) , MEDLINE(®) , MEDLINE(®) In-Process, and The Cochrane Library were searched on two occasions using MeSH terms combined with free-text terms. References were screened by two independent reviewers. Relevant publications were then extracted by two independent reviewers, with a third reviewer collating and finalising extractions.
RESULTS
The searches returned a total of 705 hits. 632 abstracts were screened after the removal of duplicates. Following screening, 35 full-length publications were reviewed. Of these, 17 were excluded, resulting in 18 studies deemed relevant for data extraction. Two were randomised controlled trials (RCTs), 16 were non-RCTs, and 10 were case reports.
DISCUSSION
Although most reports suggest that demeclocycline can address serum sodium levels in specific patients with HN, efficacy is variable, and may depend upon the underlying aetiology. Demeclocycline dose adjustments can be complex, and as its use in clinical practice is not well defined, it can differ between healthcare professionals.
CONCLUSION
There is a lack of clinical and economic evidence supporting the use of demeclocycline for HN secondary to SIADH. Patients receiving demeclocycline for HN secondary to SIADH must be closely monitored.
Topics: Demeclocycline; Humans; Hyponatremia; Inappropriate ADH Syndrome
PubMed: 26289137
DOI: 10.1111/ijcp.12713 -
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 -
Cartilage Dec 2021The temporomandibular joint (TMJ) is a unique fibrocartilaginous joint that adapts to mechanical loading through cell signaling pathways such as the Wnt pathway....
OBJECTIVE
The temporomandibular joint (TMJ) is a unique fibrocartilaginous joint that adapts to mechanical loading through cell signaling pathways such as the Wnt pathway. Increased expression of low-density lipoprotein receptor-related protein 5 (Lrp5), a co-receptor of the Wnt pathway, is associated with a high bone mass (HBM) phenotype. The objective of this study was to analyze the effect of overexpression of Lrp5 on the subchondral bone and cartilage of the TMJ in mice exhibiting the HBM phenotype.
DESIGN
Sixteen-week-old Lrp5 knock-in transgenic mice carrying either the A214V (EXP-A) or G171V (EXP-G) missense mutations, and wildtype controls (CTRL) were included in this study. Fluorescent bone labels, calcein, alizarin complexone, and demeclocycline were injected at 3.5, 7.5, and 11.5 weeks of age, respectively. The left mandibular condyle was used to compare the subchondral bone micro-computed tomography parameters and the right TMJ was used for histological analyses. Cartilage thickness, matrix proteoglycan accumulation, and immunohistochemical localization of Lrp5 and sclerostin were compared between the groups.
RESULTS
Subchondral bone volume (BV) and percent bone volume (BV/TV) were significantly increased in both EXP-A and EXP-G compared with CTRL ( < 0.05) whereas trabecular spacing (Tb.Sp) was decreased. Cartilage thickness, extracellular matrix production, and expression of Lrp5 and Sost were all increased in the experimental groups. The separation between the fluorescent bone labels indicated increased endochondral maturation between 3.5 and 7.5 weeks.
CONCLUSIONS
These data demonstrate that Lrp5 overexpression leads to adaptation changes in the mandibular condylar cartilage of the TMJ to prevent cartilage degradation.
Topics: Animals; Bone and Bones; Cartilage; Low Density Lipoprotein Receptor-Related Protein-5; Mice; Temporomandibular Joint; X-Ray Microtomography
PubMed: 33124433
DOI: 10.1177/1947603520968875 -
The Cochrane Database of Systematic... Jun 2018Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer hospital stays. Many treatments, such as fluid restriction or vasopressin receptor antagonists can be used to improve the hyponatraemia, but whether that translates into improved patient-important outcomes is less certain.
OBJECTIVES
This review aimed to 1) look at the benefits and harms of interventions for chronic non-hypovolaemic hypotonic hyponatraemia when compared with placebo, no treatment or head-to-head; and 2) determine if benefits and harms vary in absolute or relative terms dependent on the specific compound within a drug class, on the dosage used, or the underlying disorder causing the hyponatraemia.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 1 December 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also screened the reference lists of potentially relevant studies, contacted authors, and screened the websites of regulatory agencies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of any intervention with placebo, no treatment, standard care, or any other intervention in patients with chronic non-hypovolaemic hypotonic hyponatraemia. We also included subgroups with hyponatraemia from studies with broader inclusion criteria (e.g. people with chronic heart failure or people with cirrhosis with or without hyponatraemia), provided we could obtain outcomes for participants with hyponatraemia from the report or the study authors.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias. We expressed treatment effects as mean difference (MD) for continuous outcomes (health-related quality of life, length of hospital stay, change from baseline in serum sodium concentration, cognitive function), and risk ratio (RR) for dichotomous outcomes (death, response and rapid increase in serum sodium concentration, hypernatraemia, polyuria, hypotension, acute kidney injury, liver function abnormalities) together with 95% confidence intervals (CI).
MAIN RESULTS
We identified 35 studies, enrolling 3429 participants. Twenty-eight studies (3189 participants) compared a vasopressin receptor antagonist versus placebo, usual care, no treatment, or fluid restriction. In adults with chronic, non-hypovolaemic hypotonic hyponatraemia, vasopressin receptor antagonists have uncertain effects on death at six months (15 studies, 2330 participants: RR 1.11, 95% CI 0.92 to 1.33) due to risk of selective reporting and serious imprecision; and on health-related quality of life because results are at serious risk of performance, selective reporting and attrition bias, and suffer from indirectness related to the validity of the Short Form Health Survey (SF-12) in the setting of hyponatraemia. Vasopressin receptor antagonists may reduce hospital stay (low certainty evidence due to risk of performance bias and imprecision) (3 studies, 610 participants: MD -1.63 days, 95% CI -2.96 to -0.30), and may make little or no difference to cognitive function (low certainty evidence due to indirectness and imprecision). Vasopressin receptor antagonists probably increase the intermediate outcome of serum sodium concentration (21 studies, 2641 participants: MD 4.17 mmol/L, 95% CI 3.18 to 5.16), corresponding to two and a half as many people having a 5 to 6 mmol/L increase in sodium concentration compared with placebo at 4 to 180 days (moderate certainty evidence due to risk of attrition bias) (18 studies, 2014 participants: RR 2.49, 95% CI 1.95 to 3.18). But they probably also increase the risk of rapid serum sodium correction - most commonly defined as > 12 mmol/L/d (moderate certainty evidence due to indirectness) (14 studies, 2058 participants: RR 1.67, 95% CI 1.16 to 2.40) and commonly cause side-effects such as thirst (13 studies, 1666 participants: OR 2.77, 95% CI 1.80 to 4.27) and polyuria (6 studies, 1272 participants): RR 4.69, 95% CI 1.59 to 13.85) (high certainty evidence). The potential for liver toxicity remains uncertain due to large imprecision. Effects were generally consistent across the different agents, suggesting class effect.Data for other interventions such as fluid restriction, urea, mannitol, loop diuretics, corticosteroids, demeclocycline, lithium and phenytoin were largely absent.
AUTHORS' CONCLUSIONS
In people with chronic hyponatraemia, vasopressin receptor antagonists modestly raise serum sodium concentration at the cost of a 3% increased risk of it being rapid. To date there is very low certainty evidence for patient-important outcomes; the effects on mortality and health-related quality of life are unclear and do not rule out appreciable benefit or harm; there does not appear to be an important effect on cognitive function, but hospital stay may be slightly shorter, although available data are limited. Treatment decisions must weigh the value of an increase in serum sodium concentration against its short-term risks and unknown effects on patient-important outcomes. Evidence for other treatments is largely absent.Further studies assessing standard treatments such as fluid restriction or urea against placebo and one-another would inform practice and are warranted. Given the limited available evidence for patient-important outcomes, any study should include these outcomes in a standardised manner.
Topics: Antidiuretic Hormone Receptor Antagonists; Chronic Disease; Humans; Hyponatremia; Length of Stay; Quality of Life; Randomized Controlled Trials as Topic; Sodium
PubMed: 29953167
DOI: 10.1002/14651858.CD010965.pub2 -
Frontiers in Microbiology 2020Antibiotic resistance is a growing public health concern, though the constant development of new antibiotics. The combination of high-throughput screening and drug...
Antibiotic resistance is a growing public health concern, though the constant development of new antibiotics. The combination of high-throughput screening and drug repurposing is an effective way to develop new therapeutic uses of drugs. In this study, we screened a drug library consisting of 1,573 drugs already approved by the Food and Drug Administration and 903 drugs from the natural product library, to identify antimicrobials against . A high-throughput screening assay based on microtiter plate was used to screen 39 drugs that inhibit the planktonic or biofilm formation of while most of them are antibiotics. The antimicrobial activities of these drugs were evaluated by phenotypic analysis. Further studies showed the combined therapy of tetracycline antibiotics demeclocycline hydrochloride (DMCT) and the novel antimicrobial peptide SAAP-148 has an effective synergistic antibacterial effect on PAO1 and ATCC27853. Moreover, the time-kill curve assay and murine model of cutaneous abscesses further confirmed the synergistic effect. In addition, the combination of DMCT and SAAP-148 has the potential to combat clinically isolated multidrug-resistant (MDR) strains. Our results clearly indicate that DMCT and SAAP-148 combined therapy could be an effective method to combat MDR -related infections.
PubMed: 33362739
DOI: 10.3389/fmicb.2020.591426 -
Mikrochimica Acta May 2023The fabrication of iron oxide quantum dots (IO-QDs) modified with glutamic acid (Glu) under controllable conditions is reported. The IO-QDs have been characterized by...
The fabrication of iron oxide quantum dots (IO-QDs) modified with glutamic acid (Glu) under controllable conditions is reported. The IO-QDs have been characterized by transmission electron microscopy, spectrofluorometry, powder X-ray diffraction, vibrating sample magnetometry, UV-Vis spectroscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy. The IO-QDs exhibited good stability towards irradiation, temperature elevations, and ionic strength, and the quantum yield (QY) of IO-QDs was calculated to be 11.91 ± 0.09%. The IO-QDs were furtherly measured at an excitation wavelength of 330 nm with emission maxima at 402 nm, which were employed to detect tetracycline (TCy) antibiotics, including tetracycline (TCy), chlortetracycline (CTCy), demeclocycline (DmCy), and oxytetracycline (OTCy) in biological samples. The results indicated that TCy, CTCy, DmCy, and OTCy in urine samples show a dynamic working range between 0.01 and 80.0 μM; 0.01 and 1.0 μM; 0.01 and 10 μM; and 0.04 and 1.0 μM, respectively, with detection limits of 7.69 nM, 120.23 nM, 18.20 nM, and 67.74 nM, respectively. The detection was not interfered with by the auto-fluorescence from the matrices. In addition, the obtained recovery in real urine samples suggested that the developed method could be used in practical applications. Therefore, the current study has prospect to develop an easy, fast, eco-friendly, and efficient new sensing method for detecting tetracycline antibiotics in biological samples.
Topics: Quantum Dots; Glutamic Acid; Tetracycline; Anti-Bacterial Agents
PubMed: 37198413
DOI: 10.1007/s00604-023-05801-3 -
Clinical Medicine (London, England) Oct 2018A 69-year-old man developed reduced consciousness of sudden onset. Examination and parameters were normal, except for a Glasgow Coma Scale (GCS) score of six. Brain... (Review)
Review
A 69-year-old man developed reduced consciousness of sudden onset. Examination and parameters were normal, except for a Glasgow Coma Scale (GCS) score of six. Brain imaging and blood tests were also normal, except for high plasma ammonia. His past medical history included epilepsy, hypertension and colitis. He was taking multiple antiepileptic medications, including sodium valproate, with no recent dose alterations. Medical intervention led to the sodium valproate being stopped and naloxone being administered. The patient's level of responsiveness and ammonia levels gradually improved. The patient was also being treated with ciprofloxacin for a urinary tract infection and a newly developed syndrome of inappropriate antidiuretic hormone secretion treated with demeclocycline. There is an association between long-term sodium valproate use and low carnitine levels, especially in the setting of polypharmacy. This in turn precipitates hyperammonaemia and encephalopathy. This case highlights the importance of an adequate drug history and the awareness of serious but uncommon adverse effects.
Topics: Aged; Ammonia; Anticonvulsants; Brain Diseases; Carnitine; Consciousness Disorders; Epilepsy; Humans; Hyperammonemia; Male; Polypharmacy; Valproic Acid
PubMed: 30287443
DOI: 10.7861/clinmedicine.18-5-430