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Scientific Reports Aug 2023Tetracyclines exhibit anti-viral, anti-inflammatory, and immunomodulatory activities via various mechanisms. The present study investigated the efficacy and safety of... (Randomized Controlled Trial)
Randomized Controlled Trial
Tetracyclines exhibit anti-viral, anti-inflammatory, and immunomodulatory activities via various mechanisms. The present study investigated the efficacy and safety of demeclocycline in patients hospitalized with mild-to-moderate COVID-19 via an open-label, multicenter, parallel-group, randomized controlled phase 2 trial. Primary and secondary outcomes included changes from baseline (day 1, before the study treatment) in lymphocytes, cytokines, and SARS-CoV-2 RNA on day 8. Seven, seven, and six patients in the control, demeclocycline 150 mg daily, and demeclocycline 300 mg daily groups, respectively, were included in the modified intention-to-treat population that was followed until day 29. A significant change of 191.3/μL in the number of CD4 T cells from day 1 to day 8 was observed in the demeclocycline 150 mg group (95% CI 5.1/μL-377.6/μL) (p = 0.023), whereas that in the control group was 47.8/μL (95% CI - 151.2/μL to 246.8/μL), which was not significant (p = 0.271). The change rates of CD4 T cells negatively correlated with those of IL-6 in the demeclocycline-treated groups (R = - 0.807, p = 0.009). All treatment-emergent adverse events were of mild-to-moderate severity. The present results indicate that the treatment of mild-to-moderate COVID-19 patients with demeclocycline elicits immune responses conducive to recovery from COVID-19 with good tolerability.Trial registration: This study was registered with the Japan Registry of Clinical Trials (Trial registration number: jRCTs051200049; Date of the first registration: 26/08/2020).
Topics: Humans; COVID-19; Demeclocycline; RNA, Viral; SARS-CoV-2
PubMed: 37612352
DOI: 10.1038/s41598-023-41051-2 -
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 -
JAMA Aug 1974
Topics: Acne Vulgaris; Adult; Demeclocycline; Diabetes Insipidus; Female; Gonorrhea; Humans; Male; Polyuria; Vasopressins
PubMed: 4277429
DOI: No ID Found -
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 -
JAMA Jun 1980
Topics: Demeclocycline; Glomerular Filtration Rate; Humans; Hyponatremia; Kidney; Kidney Diseases; Natriuresis
PubMed: 6770107
DOI: No ID Found -
Lancet (London, England) Jan 1977
Topics: Acute Kidney Injury; Demeclocycline; Humans; Kidney Concentrating Ability; Kidney Function Tests; Liver Cirrhosis; Male; Middle Aged
PubMed: 63697
DOI: 10.1016/s0140-6736(77)91697-x -
Annals of Internal Medicine Jan 1977
Topics: Demeclocycline; Humans; Hyponatremia; Male; Middle Aged
PubMed: 402098
DOI: 10.7326/0003-4819-86-1-113 -
British Dental Journal Mar 2021
Topics: Child; Demeclocycline; Drug Combinations; Humans; Triamcinolone Acetonide
PubMed: 33712760
DOI: 10.1038/s41415-021-2796-3 -
Proceedings of the Royal Society of... Jun 1974
Topics: Adult; Demeclocycline; Humans; Male; Nails; Photosensitivity Disorders
PubMed: 4212238
DOI: No ID Found -
JAMA Jun 1977The efficacy of demeclocycline hydrochloride in suppressing the tubular action of tumoral antidiuretic products was tested in seven patients with the syndrome of...
The efficacy of demeclocycline hydrochloride in suppressing the tubular action of tumoral antidiuretic products was tested in seven patients with the syndrome of inappropriate antidiuretic hormone secretion. In all patients, demeclocycline hydrochloride (1,200 mg/day) induced production of hypotonic urine and corrected hyponatremia despite large fluid intakes. Comparison of the response to a standard water load before and during treatment showed a notable improvement in the response to water ingestion. Even though demeclocycline moderately impairs renal function, it appears to be the treatment of choice in the chronic form of the syndrome.
Topics: Administration, Oral; Aged; Carcinoma, Small Cell; Chronic Disease; Demeclocycline; Depression, Chemical; Dose-Response Relationship, Drug; Humans; Hyponatremia; Kidney Concentrating Ability; Lung Neoplasms; Male; Middle Aged; Syndrome; Vasopressins
PubMed: 194065
DOI: 10.1001/jama.237.25.2723