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Doxycycline Malaria Prophylaxis Impact on Risk of Travelers' Diarrhea among International Travelers.The American Journal of Tropical... Nov 2020International travelers are frequently at risk for travelers' diarrhea (TD) and malaria. Doxycycline was one of the earliest antibiotics shown to have efficacy in TD...
International travelers are frequently at risk for travelers' diarrhea (TD) and malaria. Doxycycline was one of the earliest antibiotics shown to have efficacy in TD prevention. With increasing resistance and recommendations against antibiotic chemoprophylaxis, doxycycline fell out of use. We evaluated TD incidence and risk factors in a prospective cohort of travelers, specifically in regard to malaria prophylaxis. Travelers' diarrhea was defined as ≥ 3 loose stools in 24 hours or two loose stools in 24 hours associated with other gastrointestinal symptoms. The Poisson regression model with robust error variance was used to estimate the RR of TD. Three thousand two hundred twenty-seven trips were enrolled: 62.1% of participants were male, with a median age of 39 years (interquartile range [IQR] 27,59) and a median travel duration of 19 days (IQR 12,49); 17.4% developed TD; 32% traveled to Africa, 40% to Asia, and 27% to the Caribbean and Latin America; and 20% took doxycycline for malaria chemoprophylaxis, 50% took other antimalarials, and 30% took none. Decreased RR of TD was associated with doxycycline (RR 0.62 [0.47-0.82], < 0.01) and military travel (RR 0.57 [0.47-0.70], < 0.01). Increased risk of TD was associated with female gender (RR 1.28 [1.09-1.50], < 0.01), hotel accommodations (RR 1.30 [1.10-1.53], < 0.01), travel to tropical South America (RR 1.34 [1.09-1.64], < 0.01), and duration of travel (RR 1.00 [1.00-1.01], < 0.01). The use of doxycycline for malaria prophylaxis is associated with lower TD risk, suggesting increasing bacterial enteropathogen susceptibility similar to previous observations. Doxycycline selection for antimalarial chemoprophylaxis may provide additional traveler benefit in infection prevention.
Topics: Adult; Anti-Bacterial Agents; Cohort Studies; Diarrhea; Doxycycline; Female; Global Health; Humans; Malaria; Male; Middle Aged; Risk Factors; Travel
PubMed: 32815505
DOI: 10.4269/ajtmh.20-0241 -
International Journal of Biological... 2016Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal...
Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal cooperation with antibiotics. A better understanding of this aspect could advance our knowledge and help improve the efficacy of current approaches towards Borrelia sp. In this study, phytochemicals and micronutrients such as baicalein, luteolin, 10-HAD, iodine, rosmarinic acid, and monolaurin, as well as, vitamins D3 and C were tested in a combinations with doxycycline for their in vitro effectiveness against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia burgdorferi and Borrelia garinii. Anti-borreliae effects were evaluated according to checkerboard assays and supported by statistical analysis. The results showed that combination of doxycycline with flavones such as baicalein and luteolin exhibited additive effects against all morphological forms of studied Borrelia sp. Doxycycline combined with iodine demonstrated additive effects against spirochetes and biofilm, whereas with fatty acids such as monolaurin and 10-HAD it produced FICIs of indifference. Additive anti-spirochetal effects were also observed when doxycycline was used with rosmarinic acid and both vitamins D3 and C. Antagonism was not observed in any of the cases. This data revealed the intrinsic anti-borreliae activity of doxycycline with tested phytochemicals and micronutrients indicating that their addition may enhance efficacy of this antibiotic in combating Borrelia sp. Especially the addition of flavones balcalein and luteolin to a doxycycline regimen could be explored further in defining more effective treatments against these bacteria.
Topics: Anti-Infective Agents; Biofilms; Borrelia; Borrelia burgdorferi; Borrelia burgdorferi Group; Doxycycline; Microbial Sensitivity Tests; Micronutrients; Phytochemicals; Spirochaetales
PubMed: 27570483
DOI: 10.7150/ijbs.16060 -
BMJ Case Reports Dec 2021A 64-year-old woman presented with 24 hours of lethargy, confusion, headache, nausea and vomiting. Examination revealed expressive aphasia, conjunctival suffusion and a...
A 64-year-old woman presented with 24 hours of lethargy, confusion, headache, nausea and vomiting. Examination revealed expressive aphasia, conjunctival suffusion and a tick embedded in her popliteal fossa. Labs revealed hyponatraemia, transaminitis, leucopenia, thrombocytopenia and an elevated C reactive protein. Peripheral blood smear was unremarkable. MRI/magnetic resonance angiogram revealed bilateral frontoparietal subarachnoid haemorrhage which was further confirmed by lumbar puncture which revealed six nucleated cells, 92% lymphocytes, 1460 red blood cells, normal glucose and protein and negative cryptococcal antigen, herpes simplex PCR and Lyme PCR. Serum Lyme IgG/IgM antibodies and PCR, serum IgG/IgM antibodies and PCR and anaplasma serum IgG/IgM antibodies were negative. Anaplasmosis serum PCR was positive. The tick was identified as The patient was diagnosed with anaplasmosis and treated with 21 days of doxycycline resulting in improvement of symptoms, but lingering headaches and word finding difficulties.
Topics: Anaplasma phagocytophilum; Anaplasmosis; Animals; Central Nervous System; Doxycycline; Female; Humans; Ixodes; Middle Aged
PubMed: 34880034
DOI: 10.1136/bcr-2021-243665 -
International Journal of Molecular... Feb 2024Periodontitis is a complex condition. Left untreated, it leads to tooth loss and the need for prosthetic treatment. The incidence of periodontitis is steadily... (Review)
Review
Periodontitis is a complex condition. Left untreated, it leads to tooth loss and the need for prosthetic treatment. The incidence of periodontitis is steadily increasing, so new methods are being sought to aid in the diagnosis of the disease. Among the methods postulated is the determination of concentrations of bioactive compounds which include extracellular matrix metalloproteinases (MMPs). These enzymes are present in various structural elements of the stomatognathic system. The most promising enzyme of this group appears to be metalloproteinase 8 (MMP-8). MMP-8 assays are performed in gingival fluid or saliva, and MMP-8 levels have been shown to be higher in patients with periodontitis compared to healthy subjects and correlated with some clinical parameters of the condition and the severity of the disease. In addition, the preliminary usefulness of this enzyme in evaluating the effectiveness of periodontal treatment and doxycycline therapy has been demonstrated. Determination of the active form of MMP-8 (aMMP-8) in oral rinse fluid using off-the-shelf assays shows the highest potential. Despite reports about aMMP-8 and promising data on the role of MMP-8 in periodontal diagnosis, a clear determination of the usefulness of this enzyme requires further research.
Topics: Humans; Matrix Metalloproteinase 8; Gingival Crevicular Fluid; Periodontitis; Doxycycline
PubMed: 38473967
DOI: 10.3390/ijms25052721 -
PloS One 2015Cancer stem cells (CSCs) are proposed to be responsible for high recurrence rate in cervical carcinoma. Reagents that can suppress the proliferation and differentiation...
BACKGROUND
Cancer stem cells (CSCs) are proposed to be responsible for high recurrence rate in cervical carcinoma. Reagents that can suppress the proliferation and differentiation of CSCs would provide new opportunities to fight against tumor recurrence. Doxycycline has been reported as a potential anti-cancer compound. However, few studies investigated its inhibitory effect against cervical cancer stem cells.
METHODS
HeLa cells were cultured in cancer stem cell conditional media in a poly-hema-treated dish. In this non-adhesive culture system, HeLa cells were treated with cisplatin until some cells survived and formed spheroids, which were then collected and injected into the immunodeficient mice. Cisplatin was administered every three days for five times. The tumor xenografts with CSC enrichment were cultured in cancer stem cell specific medium again to form tumorsphere, which we called HeLa-CSCs. Expression of cancer stem cell markers in HeLa-CSCs was measured by flow cytometry and qPCR. HeLa-CSCs were then treated with doxycycline. Proliferation and differentiation rates were determined by the size of spheres formed in vitro and tumor formed in vivo.
RESULTS
We developed a new strategy to selectively enrich CSCs from human cervical carcinoma cell line HeLa, and these HeLa-CSCs are CD133+/CD49f+ cell populations with significantly enhanced expression of stem cell markers. When these HeLa-CSCs were treated with doxycycline, the colony formation, proliferation, migration and invasion, and differentiation were all suppressed. Meanwhile, stem cell markers SOX-2, OCT-4, NANOG, NOTCH and BMI-1 decreased in doxycycline treated cells, so as the surface markers CD133 and CD49f. Furthermore, proliferation markers Ki67 and PCNA were also decreased by doxycycline treatment in the in vivo xenograft mouse model.
CONCLUSIONS
Cancer stem cells are enriched from sphere-forming and chemoresistant HeLa-derived tumor xenografts in immunodeficient mice. Doxycycline inhibits proliferation, invasion, and differentiation, and also induces apoptosis of these HeLa-CSCs in vitro and in vivo.
Topics: Animals; Apoptosis; Cell Movement; Cell Proliferation; Cisplatin; Culture Media, Conditioned; Doxycycline; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Mice; Neoplasm Invasiveness; Neoplastic Stem Cells; Uterine Cervical Neoplasms; Xenograft Model Antitumor Assays
PubMed: 26111245
DOI: 10.1371/journal.pone.0129138 -
The Journal of Clinical Investigation Aug 2021Pulmonary cavitation is a hallmark of Mycobacterium tuberculosis (Mtb) infection that provides an immune-privileged niche for extracellular bacillary replication, which...
Pulmonary cavitation is a hallmark of Mycobacterium tuberculosis (Mtb) infection that provides an immune-privileged niche for extracellular bacillary replication, which associates with increased transmission rates, drug resistance, and chronic lung dysfunction following antituberculous therapy (ATT). Inhibitors of matrix metalloproteinases (MMPs), which are induced by Mtb infection, have shown efficacy in preclinical models and improved microbiologic and immunopathologic outcomes. In this issue of the JCI, Hao Miow et al. performed a double-blind, randomized controlled trial exploring host-directed effects of the MMP inhibitor doxycycline versus placebo when added to standard ATT for pulmonary tuberculosis. Doxycycline treatment over two weeks durably modulated host blood transcription profiles, including the resolution of inflammatory gene programs. Reduced immunopathology markers in doxycycline-treated participants also included improved lung cavity volumes and lower MMP levels in blood and sputum. These findings provide mechanistic insight and momentum for using experimental medicine trials to develop host-directed therapies for tuberculosis.
Topics: Double-Blind Method; Doxycycline; Humans; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis, Pulmonary
PubMed: 34338231
DOI: 10.1172/JCI151668 -
Clinical Infectious Diseases : An... Sep 2023Pre-existing tetracycline resistance in Neisseria gonorrhoeae limits the effectiveness of post-exposure prophylaxis (PEP) with doxycycline against gonorrhea, and...
Pre-existing tetracycline resistance in Neisseria gonorrhoeae limits the effectiveness of post-exposure prophylaxis (PEP) with doxycycline against gonorrhea, and selection for tetracycline resistance may influence prevalence of multi-drug resistant strains. Using genomic and antimicrobial susceptibility data from N. gonorrhoeae, we assessed the near-term impact of doxycycline PEP on N. gonorrhoeae resistance.
Topics: Humans; Neisseria gonorrhoeae; Anti-Bacterial Agents; Doxycycline; Post-Exposure Prophylaxis; Microbial Sensitivity Tests; Drug Resistance, Bacterial; Gonorrhea; Genomics; Tetracycline
PubMed: 37138444
DOI: 10.1093/cid/ciad279 -
Molecular Metabolism Jul 2022Tamoxifen is widely used for inducible Cre-LoxP systems but has several undesirable side effects for researchers investigating metabolism or energy balance, including...
OBJECTIVE
Tamoxifen is widely used for inducible Cre-LoxP systems but has several undesirable side effects for researchers investigating metabolism or energy balance, including weight loss, lipoatrophy, and drug incorporation into lipid stores. For this reason, we sought to determine whether a doxycycline-inducible system would be more advantageous for adipocyte-specific Cre mouse models, but serendipitously discovered widespread ectopic tetracycline response element Cre (TRE-Cre) recombinase activity.
METHODS
Adipocyte-specific tamoxifen- and doxycycline-inducible Cre mice were crossed to fluorescent Cre reporter mice and visualized by confocal microscopy to assess efficiency and background activity. TRE-Cre mice were crossed to stop-floxed diphtheria toxin mice to selectively ablate cells with background Cre activity.
RESULTS
Tamoxifen- and doxycycline-inducible systems performed similarly in adipose tissues, but ectopic Cre recombination was evident in numerous other cell types of the latter, most notably neurons. The source of ectopic Cre activity was isolated to the TRE-Cre transgene, driven by the pTet (tetO7) tetracycline-inducible promoter. Ablation of cells with ectopic recombination in mice led to stunted growth, diminished survival, and reduced brain mass.
CONCLUSIONS
These results indicate that tamoxifen- and doxycycline-inducible adipocyte-specific Cre mouse models are similarly efficient, but the TRE-Cre component of the latter is inherently leaky. TRE-Cre background activity is especially pronounced in the brain and peripheral nerve fibers, and selective ablation of these cells impairs mouse development and survival. Caution should be taken when pairing TRE-Cre with floxed alleles that have defined roles in neural function, and additional controls should be included when using this model system.
Topics: Animals; Anti-Bacterial Agents; Doxycycline; Integrases; Mice; Mice, Transgenic; Recombination, Genetic; Response Elements; Tamoxifen; Trans-Activators
PubMed: 35452876
DOI: 10.1016/j.molmet.2022.101501 -
International Journal of Molecular... Jan 2023Melanoma is still one of the most dangerous cancers. New methods of treatment are sought due to its high aggressiveness and the relatively low effectiveness of...
The Assessment of the Phototoxic Action of Chlortetracycline and Doxycycline as a Potential Treatment of Melanotic Melanoma-Biochemical and Molecular Studies on COLO 829 and G-361 Cell Lines.
Melanoma is still one of the most dangerous cancers. New methods of treatment are sought due to its high aggressiveness and the relatively low effectiveness of therapies. Tetracyclines are drugs exhibiting anticancer activity. Previous studies have also shown their activity against melanoma cells. The possibility of tetracycline accumulation in pigmented tissues and the increase in their toxicity under the influence of UVA radiation creates the possibility of developing a new anti-melanoma therapy. This study aimed to analyze the phototoxic effect of doxycycline and chlortetracycline on melanotic melanoma cells COLO 829 and G-361. The results indicated that tetracycline-induced phototoxicity significantly decreased the number of live cells by cell cycle arrest as well as a decrease in cell viability. The simultaneous exposure of cells to drugs and UVA caused the depolarization of mitochondria as well as inducing oxidative stress and apoptosis. It was found that the combined treatment activated initiator and effector caspases, caused DNA fragmentation and elevated p53 level. Finally, it was concluded that doxycycline demonstrated a stronger cytotoxic and phototoxic effect. UVA irradiation of melanoma cells treated with doxycycline and chlortetracycline allows for the reduction of therapeutic drug concentrations and increases the effectiveness of tested tetracyclines.
Topics: Humans; Doxycycline; Chlortetracycline; Tetracycline; Melanoma; Dermatitis, Phototoxic; Ultraviolet Rays; Tetracyclines; Anti-Bacterial Agents; Photosensitizing Agents; Cell Line
PubMed: 36768675
DOI: 10.3390/ijms24032353 -
Poultry Science May 2016The excretion rates and ecological risk to the environment of three commonly used veterinary antibiotics (VAs), amoxicillin, ciprofloxacin, and doxycycline, in layer hen... (Randomized Controlled Trial)
Randomized Controlled Trial
The excretion rates and ecological risk to the environment of three commonly used veterinary antibiotics (VAs), amoxicillin, ciprofloxacin, and doxycycline, in layer hen manure during the application and withdrawal periods were investigated in a study consisting of a control group fed with VA-free basal diet and nine treatment groups consisted of three levels (200 mg/kg, 100 mg/kg, and 50 mg/kg) of amoxicillin (AMX), ciprofloxacin (CIP), or doxycycline (DOC). Each treatment group was replicated seven times with three layer hens per replication. Results of the study showed that the average excretion rates of AMX in the 200, 100, and 50 mg/kg groups were 67.88, 55.82, and 66.15%, respectively, while those for CIP and DOC were 47.84, 51.85, and 44.87% and 82.67, 94.39, and 95.72%, respectively. The concentrations of the above veterinary drugs in manure decreased sharply in the withdrawal period (7, 28, and 10 d, respectively), for AMX, DOC, and CIP. Neither AMX nor DOC was detected in the manure after the withdrawal period. In contrast to AMX and DOC, the excretion rate of CIP was significantly lower and thus had a longer residence time. Ecological risk study, estimated using hazard quotient values, showed that AMX in the 100 and 50 mg/kg groups posed no risk to the environment after d 1 of withdrawal, while CIP in the 50 mg/kg group posed no risk to the environment from d 5 of withdrawal. CIP in the 200 and 100 mg/kg groups required 10 d withdrawal in order to pose no risk to the environment. In contrast, DOC residue during withdrawal in the manure posed no risk to the environment, thus making it more environmentally safe.
Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Chickens; Ciprofloxacin; Dose-Response Relationship, Drug; Doxycycline; Feces; Female; Oviposition; Time Factors
PubMed: 26944981
DOI: 10.3382/ps/pew013