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Scientific Reports Mar 2022The main objective of this study was to determine the cellular and molecular effects of doxycycline on the blood-brain barrier (BBB) and protection against secondary...
The main objective of this study was to determine the cellular and molecular effects of doxycycline on the blood-brain barrier (BBB) and protection against secondary injuries following traumatic brain injury (TBI). Microvascular hyperpermeability and cerebral edema resulting from BBB dysfunction after TBI leads to elevation of intracranial pressure, secondary brain ischemia, herniation, and brain death. There are currently no effective therapies to modulate the underlying pathophysiology responsible for TBI-induced BBB dysfunction and hyperpermeability. The loss of BBB integrity by the proteolytic enzyme matrix metalloproteinase-9 (MMP-9) is critical to TBI-induced BBB hyperpermeability, and doxycycline possesses anti-MMP-9 effect. In this study, the effect of doxycycline on BBB hyperpermeability was studied utilizing molecular modeling (using Glide) in silico, cell culture-based models in vitro, and a mouse model of TBI in vivo. Brain microvascular endothelial cell assays of tight junction protein immunofluorescence and barrier permeability were performed. Adult C57BL/6 mice were subjected to sham versus TBI with or without doxycycline treatment and immediate intravital microscopic analysis for evaluating BBB integrity. Postmortem mouse brain tissue was collected to measure MMP-9 enzyme activity. It was found that doxycycline binding to the MMP-9 active sites have binding affinity of -7.07 kcal/mol. Doxycycline treated cell monolayers were protected from microvascular hyperpermeability and retained tight junction integrity (p < 0.05). Doxycycline treatment decreased BBB hyperpermeability following TBI in mice by 25% (p < 0.05). MMP-9 enzyme activity in brain tissue decreased with doxycycline treatment following TBI (p < 0.05). Doxycycline preserves BBB tight junction integrity following TBI via inhibiting MMP-9 activity. When established in human subjects, doxycycline, may provide readily accessible medical treatment after TBI to attenuate secondary injury.
Topics: Animals; Blood-Brain Barrier; Brain; Brain Injuries, Traumatic; Doxycycline; Humans; Mice; Mice, Inbred C57BL
PubMed: 35354869
DOI: 10.1038/s41598-022-09394-4 -
The American Journal of Medicine Jun 2018
Topics: Anti-Bacterial Agents; Doxycycline; Humans; Infectious Disease Medicine; Mass Media; Post-Lyme Disease Syndrome; Practice Guidelines as Topic; Societies, Medical
PubMed: 29284115
DOI: 10.1016/j.amjmed.2017.11.050 -
Bioorganic & Medicinal Chemistry Letters Jul 2019Chemotherapy is one of the standard methods for the treatment of malignant tumors. It aims to cause lethal damage to cellular structures, mainly DNA. Noteworthy, in... (Review)
Review
Chemotherapy is one of the standard methods for the treatment of malignant tumors. It aims to cause lethal damage to cellular structures, mainly DNA. Noteworthy, in recent years discoveries of novel anticancer agents from well-known antibiotics have opened up new treatment pathways for several cancer diseases. The aim of this review article is to describe new applications for the following antibiotics: doxycycline (DOX), salinomycin (SAL), monensin (MON) and ivermectin (IVR) as they are known to show anti-tumor activity, but have not yet been introduced into standard oncological therapy. To date, these agents have been used for the treatment of a broad-spectrum of bacterial and parasitic infectious diseases and are widely available, which is why they were selected. The data presented here clearly show that the antibiotics mentioned above should be recognised in the near future as novel agents able to eradicate cancer cells and cancer stem cells (CSCs) across several cancer types.
Topics: Antineoplastic Agents; Doxycycline; Humans; Ivermectin; Monensin; Neoplasms; Pyrans
PubMed: 31054863
DOI: 10.1016/j.bmcl.2019.04.045 -
Molecules (Basel, Switzerland) Aug 2021In this study, broilers were fed with heavy-metal-containing diets (Zn, Cu, Pb, Cr, As, Hg) at three rates (T1: 5 kg premix/ton feed, T2: 10 kg premix/ton feed and T3:...
In this study, broilers were fed with heavy-metal-containing diets (Zn, Cu, Pb, Cr, As, Hg) at three rates (T1: 5 kg premix/ton feed, T2: 10 kg premix/ton feed and T3: 15 kg premix/ton feed) and Doxycycline (DOX) and Gatifloxacin (GAT) at low or high doses (T4: 31.2 mg DOX/bird/day and 78 mg GAT/bird/day, T5: 15.6 mg DOX/bird/day and 48 mg GAT/bird/day) to assess the accumulation of various heavy metals and the fate of two antibiotics in broiler manure after 35 days of aerobic composting. The results indicated that the two antibiotics changed quite differently during aerobic composting. About 14.96-15.84% of Doxycycline still remained at the end of composting, while Gatifloxacin was almost completely removed within 10 days of composting. The half-lives of Doxycycline were 13.75 and 15.86 days, while the half-lives of Gatifloxacin were only 1.32 and 1.38 days. Based on the Redundancy analysis (RDA), the concentration of antibiotics was significantly influenced by physico-chemical properties (mainly temperature and pH) throughout the composting process. Throughout the composting process, all heavy metal elements remained concentrated in organic fertilizer. In this study the Cr content reached 160.16 mg/kg, 223.98 mg/kg and 248.02 mg/kg with increasing premix feed rates, similar to Zn, which reached 258.2 mg/kg, 312.21 mg/kg and 333.68 mg/kg. Zn and Cr concentrations well exceeded the United States and the European soil requirements. This experiment showed that antibiotic residues and the accumulation of heavy metals may lead to soil contamination and pose a risk to the soil ecosystem.
Topics: Animals; Composting; Doxycycline; Gatifloxacin; Manure; Metals, Heavy
PubMed: 34500659
DOI: 10.3390/molecules26175225 -
Clinical Infectious Diseases : An... Aug 2022Despite clinical practice guideline recommendations to use doxycycline as part of combination therapy for some patients hospitalized with pneumonia, there is minimal... (Observational Study)
Observational Study
BACKGROUND
Despite clinical practice guideline recommendations to use doxycycline as part of combination therapy for some patients hospitalized with pneumonia, there is minimal evidence supporting this recommendation. Our aim was to examine the association between beta-lactam plus doxycycline and mortality for patients hospitalized with community-acquired pneumonia.
METHODS
We identified patients >65 years of age admitted to any US Department of Veterans Affairs hospital in fiscal years 2002-2012 with a discharge diagnosis of pneumonia. We excluded those patients who did not receive antibiotic therapy concordant with the 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) clinical practice guidelines. Using propensity score matching, we examined the association of doxycycline with 30- and 90-day mortality.
RESULTS
Our overall cohort was comprised of 70533 patients and 5282 (7.49%) received doxycycline. Unadjusted 30-day mortality was 6.4% for those who received a beta-lactam plus doxycycline versus 9.1% in those who did not (P < .0001), and 90-day mortality was 13.8% for those who received a beta-lactam + doxycycline versus 16.8% for those who did not (P < .0001). In the propensity score matched models, both 30- (odds ratio 0.72, 95% confidence interval [CI], .63-.84) and 90-day (0.83, 95% CI, .74-.92) mortality were significantly lower for those who received doxycycline.
CONCLUSIONS
In this retrospective observational cohort study, we found that doxycycline use, as part of guideline-concordant antibiotic therapy, was associated with lower 30- and 90-day mortality than regimens without doxycycline. While this supports the safety and effectiveness of antibiotic regimes that include doxycycline, additional studies, especially randomized clinical trials, are needed to confirm this.
Topics: Anti-Bacterial Agents; Community-Acquired Infections; Doxycycline; Drug Therapy, Combination; Humans; Pneumonia; Retrospective Studies; beta-Lactams
PubMed: 34751745
DOI: 10.1093/cid/ciab863 -
The Cochrane Database of Systematic... Jun 2021Posterior blepharitis is common and causes ocular surface and lid damage as well as discomfort. It affects 37% to 47% of all ophthalmology patients; its incidence...
BACKGROUND
Posterior blepharitis is common and causes ocular surface and lid damage as well as discomfort. It affects 37% to 47% of all ophthalmology patients; its incidence increasing with age. It is a multifactorial disease associated with multiple other pathologies, such as rosacea, meibomianitis, and infections. Treatment usually focuses on reliefing the symptoms by using artificial tears, lid scrubs, and warm compresses. The condition may be notoriously difficult to manage adequately once it becomes chronic. One such management approach for chronic blepharitis is the use of oral antibiotics for both their antibacterial as well as anti-inflammatory properties. There are currently no guidelines regarding the use of oral antibiotics, including antibiotic type, dosage, and treatment duration, for the treatment of chronic blepharitis.
OBJECTIVES
To assess the benefits and harms of oral antibiotic use for people with chronic blepharitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 8); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 29 August 2020.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing oral antibiotics with placebo in adult participants with chronic blepharitis (including staphylococcal, seborrhoeic, or Meibomian Gland Dysfunction (MGD)).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology and graded the certainty of the body of evidence for six outcomes using the GRADE classification.
MAIN RESULTS
We included two studies with 220 participants (numbers of eyes unclear). One parallel-group RCT comparing oral doxycycline (40 mg once a day) with placebo enrolled 70 participants with blepharitis and facial rosacea in the USA. Follow-up duration was three months. One three-arm RCT conducted in South Korea investigated the effect of high-dose (200 mg twice a day) and low-dose (20 mg twice a day) doxycycline versus placebo after one month of study medication. It enrolled 50 participants with chronic MGD in each study arm (i.e. 150 participants enrolled in total). The two studies did not evaluate the same outcome measurements, which precluded any meta-analysis. The evidence for the effect of oral antibiotics on subjective improvement in symptoms was very uncertain. One study suggested that there was little to no effect of oral doxycycline on subjective symptoms based on the Ocular Surface Disease Index (OSDI) scores ranging from 0 to 100 (higher score indicates worse condition) (mean difference (MD) 3.55, 95% confidence interval (CI) -4.61 to 11.71; n = 70) and bulbar conjunctival hyperemia ranging from 0 (clear) to 4 (severe) (MD -0.01, 95% CI -0.38 to 0.36; n = 70) at 12 weeks. The three-arm RCT showed that oral doxycycline may slightly improve number of symptoms (MD -0.56, 95% CI -0.95 to -0.17; n = 93 (high-dose doxycycline versus placebo); MD -0.48, 95% CI -0.86 to -0.10; n = 93 (low-dose doxycycline versus placebo)) and proportion of participants with symptom improvement (risk ratio (RR) 6.13, 95% CI 2.61 to 14.42; n = 93 (high-dose doxycycline versus placebo); RR 6.54, 95% CI 2.79 to 15.30; n = 93 (low-dose doxycycline versus placebo)) at one month, but the evidence is very uncertain. We judged the certainty of evidence for subjective symptoms as very low. One study evaluated aqueous tear production by Schirmer's test (mm/5 min) (higher score indicates better condition) and tear film stability by measuring tear film break-up time (TBUT) in seconds (higher score indicates better condition) at one month. We found very low certainty evidence that oral doxycycline may improve these clinical signs. The estimated MD in Schirmer's test score after one month of treatment was 4.09 mm (95% CI 2.38 to 5.80; n = 93) in the high-dose doxycycline group versus the placebo group and 3.76 mm (95% CI 1.85 to 5.67; n = 93) in the low-dose doxycycline group versus the placebo group. The estimated MD in TBUT after one month was 1.58 seconds (95% CI 0.57 to 2.59; n = 93) when comparing the high-dose doxycycline group with the placebo group, and 1.70 seconds (95% CI 0.96 to 2.44; n = 93) when comparing the low-dose doxycycline group with the placebo group. Although there was a noted improvement in these scores, their clinical importance remains uncertain. One study suggested that oral doxycycline may increase the incidence of serious side effects: 18 (39%) participants in the high-dose doxycycline group, 8 (17%) in the low-dose doxycycline group, and 3 (6%) out of 47 participants in the placebo group experienced serious side effects (RR 6.13, 95% CI 1.94 to 19.41; n = 93 (high-dose doxycycline versus placebo); RR 2.72, 95% CI 0.77 to 9.64; n = 93 (low-dose doxycycline versus placebo)). Additionally, one study reported that one case of migraine headache and five cases of headache were observed in the oral doxycycline group, and one case of non-Hodgkin's lymphoma was observed in the placebo group. We judged the certainty of evidence for adverse events as very low.
AUTHORS' CONCLUSIONS
There was insufficient evidence to draw any meaningful conclusions on the use of oral antibiotics for chronic blepharitis. Very low certainty evidence suggests that oral antibiotics may improve clinical signs, but may cause more adverse events. The evidence for the effect of oral antibiotics on subjective symptoms is very uncertain. Further trials are needed to provide high quality evidence on the use of oral antibiotics in the treatment of chronic blepharitis.
Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Bias; Blepharitis; Chronic Disease; Doxycycline; Drug Administration Schedule; Humans; Randomized Controlled Trials as Topic
PubMed: 34107053
DOI: 10.1002/14651858.CD013697.pub2 -
Sexually Transmitted Diseases Sep 2021Editorial for Sexually Transmitted Diseases (STD20–495): Interest, concerns, and attitudes among men who have sex with men and healthcare providers toward prophylactic...
Editorial for Sexually Transmitted Diseases (STD20–495): Interest, concerns, and attitudes among men who have sex with men and healthcare providers toward prophylactic use of doxycycline against infections and syphilis.
Topics: Chlamydia Infections; Doxycycline; Humans; Sexually Transmitted Diseases
PubMed: 34117188
DOI: 10.1097/OLQ.0000000000001501 -
Current Molecular Medicine 2022The antibacterial mechanism of doxycycline is known, but its effects on the nerve-muscle system are still not unclear.
BACKGROUND
The antibacterial mechanism of doxycycline is known, but its effects on the nerve-muscle system are still not unclear.
OBJECTIVE
The aim of the study was to combine molecular targets of the neuromuscular machinery using the in situ neuronal blocker effect of doxycycline, a semisynthetic second-generation tetracycline derivative, on mice neuromuscular preparations.
METHODS
The effects of doxycycline were assessed on presynaptic, synaptic cleft, and postsynaptic neurotransmission, along with the muscle fiber, using the traditional myographic technique. Precisely, the effects of doxycycline were categorized into "all" or "nothing" effects depending on the concentration of doxycycline used; "all" was obtained with 4 μM doxycycline, and "nothing" was obtained with 1-3 μM doxycycline. The rationale of this study was to apply known pharmacological tools against the blocker effect of 4 μM doxycycline, such as F55-6 (Casearia sylvestris), CaCl (or Ca), atropine, neostigmine, polyethylene glycol (PEG 400), and d-Tubocurarine. The evaluation of cholinesterase enzyme activity and the diaphragm muscle histology were performed, and protocols on the neuromuscular preparation submitted to indirect or direct stimuli were complementary.
RESULTS
Doxycycline does not affect cholinesterase activity nor causes damage to skeletal muscle diaphragm; it acts on ryanodine receptor, sarcolemmal membrane, and neuronal sodium channel with a postjunctional consequence due to the decreased availability of muscle nicotinic acetylcholine receptors.
CONCLUSION
In conclusion, in addition to the neuronal blocker effect of doxycycline, we showed that doxycycline acts on multiple targets. It is antagonized by F55-6, a neuronal Na+-channel agonist, and Ca, but not by neostigmine.
Topics: Animals; Cholinesterases; Doxycycline; Mice; Muscle Contraction; Neostigmine; Neuromuscular Junction; Phrenic Nerve
PubMed: 34355683
DOI: 10.2174/1566524021666210521125553 -
Expert Review of Anti-infective Therapy Aug 2021: COVID-19 infection with no known-specific drugs or vaccines has impacted mankind and has become beyond precedence. Currently, re-purposing of existing drugs is the... (Review)
Review
: COVID-19 infection with no known-specific drugs or vaccines has impacted mankind and has become beyond precedence. Currently, re-purposing of existing drugs is the only therapeutic option for managing COVID-19 symptoms and associated co-infections to reduce mortality. Antimicrobials as varied as antiparasitic, antiviral, and antibiotics are under various stages of evaluation.: Recently, doxycycline, a broad-spectrum antibiotic that has also reported antiviral and anti-inflammatory properties was widely investigated in clinical trials, either alone or in combination with other drugs, and repurposed for COVID-19 treatment. In the review, the potential therapeutic applications of doxycycline in COVID-19 treatment and its potential adverse implications with respect to antimicrobial resistance bestowed by repurposing the antibiotic have been expounded.: 'Fighting disease with already existing antibiotics' and 'antimicrobial resistance progression' are like two arms of a balance that has to be carefully equilibrated. Any imbalance by the inappropriate or indiscriminate use of the repurposed drugs would cause a disastrous increase in antimicrobial resistance (AMR). Hence, cautious parallel assessment of potential long-term consequences of AMR is of great importance to mankind as its impacts would prevail even after the current pandemic.
Topics: Anti-Bacterial Agents; Antiviral Agents; Doxycycline; Drug Repositioning; Humans; Pandemics; COVID-19 Drug Treatment
PubMed: 33322952
DOI: 10.1080/14787210.2021.1865803 -
Journal of Pediatric Surgery Dec 2015This is a systematic review of the literature describing doxycycline sclerotherapy (DS) to treat pediatric head and neck lymphatic malformations and examine patient... (Review)
Review
OBJECTIVE
This is a systematic review of the literature describing doxycycline sclerotherapy (DS) to treat pediatric head and neck lymphatic malformations and examine patient factors associated with treatment success.
DATA SOURCES
PubMed, EMBASE, and Ovid.
REVIEW METHODS
A query of PubMed, EMBASE, and Ovid search engines (1995-2014) for studies examining outcomes for doxycycline sclerotherapy (DS) as primary treatment strategy for children with head and neck lymphatic malformations was undertaken. Successful outcome was defined as clinical resolution of symptoms or greater than 50% reduction in radiographic involvement.
RESULTS
Five studies met the inclusion criteria for review. All were retrospective case series reports with high risk of bias. The dose of doxycycline used in all but one of the studies was 10mg/mL, and the highest concentration administered was 20mg/mL. Thirty-eight children met the inclusion criteria for analysis. Thirty-two (84.2%) children were successfully treated with DS, with 23 (60.5%) utilizing only one treatment session. Average follow-up was 9.7months. Age, gender, de Serres stage 1, and type of lymphatic malformation were not related to successful treatment outcome (p=0.23, 1, 1, and 0.13, respectively).
CONCLUSIONS
DS is very effective for treatment of macrocystic and mixed head and neck lymphatic malformations in children. Overall success with DS treatment in children with lymphatic malformation of the head and neck was 84.2%. DS has distinct advantages over other sclerotherapy agents including that it is inexpensive and widely available, and has minimal side effects. No associated patient characteristics were found to predict improved success.
Topics: Adolescent; Child; Doxycycline; Female; Head; Humans; Infant; Lymphatic Abnormalities; Male; Neck; Sclerosing Solutions; Sclerotherapy; Treatment Outcome
PubMed: 26421368
DOI: 10.1016/j.jpedsurg.2015.08.051