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Sample records for subantimicrobial dose doxycycline

  1. Efficacy of short-term adjunctive subantimicrobial dose doxycycline in diabetic patients--randomized study.

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    Gilowski, L; Kondzielnik, P; Wiench, R; Płocica, I; Strojek, K; Krzemiński, T F

    2012-11-01

    To investigate the effectiveness of short-term adjunctive subantimicrobial dose doxycycline (SDD) treatment in patients with diabetes mellitus type 2 and chronic periodontitis (CP). Thirty-four patients with CP and type 2 diabetes mellitus were included in the placebo-controlled, double-blind study. After scaling and root planing (SRP), patients were randomly assigned to two groups, receiving either SDD or placebo bid for 3 months. The probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), approximal plaque index, glycated hemoglobin (HbA1c) level were recorded and gingival crevicular fluid (GCF) samples were collected at baseline and after 3-month therapy for the estimation of matrix metalloproteinase-8 levels. Clinical attachment level, PD, and BOP improved significantly in both groups after therapy (P diabetes and CP. © 2012 John Wiley & Sons A/S.

  2. Clinical and microbiological effects of a subantimicrobial dose of oral doxycycline on periodontitis in dogs.

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    Kim, S E; Hwang, S Y; Jeong, M; Lee, Y; Lee, E R; Park, Y W; Ahn, J S; Kim, S; Seo, K

    2016-02-01

    Doxycycline is regarded as an effective treatment for periodontal inflammation. In humans, it has been shown that the long-term administration of a subantimicrobial dose of doxycycline (SDD) does not induce antimicrobial effects on the subgingival microflora and furthermore does not affect antimicrobial susceptibility. The present study was designed to evaluate the influence of oral administration of SDD on normal periodontal microflora and antimicrobial susceptibility in dogs. Experimental periodontitis was induced in 12 experimental dogs using a silk and wire-twisted ligature for 60 days. After the periodontitis induction period, the ligature was removed, and dental cleaning (subgingival and supragingival ultrasonic scaling) was performed. The dogs were randomly assigned to one of two groups: an SDD group with six dogs receiving 2 mg/kg PO once daily and a control group with six dogs receiving a placebo. At weeks 0, 4 and 8, clinical periodontal parameters were evaluated. After the clinical assessments, subgingival plaque was sampled and then cultured in an anaerobic system for one week, and the total anaerobes, Porphyromonas spp., Bacteroides spp. and Pasteurella spp. counts were investigated. Using the agar dilution method, the minimum bactericidal concentration of doxycycline was evaluated and the resistance for doxycycline was monitored during this experimental phase. The clinical periodontal status of the SDD group was significantly improved compared to the control group (P  0.05), and antibacterial resistance was not established in the SDD group during the experimental periods (P <0.05). These results suggest that the once daily oral regimen of 2 mg/kg of doxycycline could serve as a SDD in dogs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. A regulatable AAV vector mediating GDNF biological effects at clinically-approved sub-antimicrobial doxycycline doses

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    Abdelwahed Chtarto

    2016-01-01

    Full Text Available Preclinical and clinical data stress the importance of pharmacologically-controlling glial cell line-derived neurotrophic factor (GDNF intracerebral administration to treat PD. The main challenge is finding a combination of a genetic switch and a drug which, when administered at a clinically-approved dose, reaches the brain in sufficient amounts to induce a therapeutic effect. We describe a highly-sensitive doxycycline-inducible adeno-associated virus (AAV vector. This vector allowed for the first time a longitudinal analysis of inducible transgene expression in the brain using bioluminescence imaging. To evaluate the dose range of GDNF biological activity, the inducible AAV vector (8.0 × 109 viral genomes was injected in the rat striatum at four delivery sites and increasing doxycycline doses administered orally. ERK/Akt signaling activation as well as tyrosine hydroxylase downregulation, a consequence of long-term GDNF treatment, were induced at plasmatic doxycycline concentrations of 140 and 320 ng/ml respectively, which are known not to increase antibiotic-resistant microorganisms in patients. In these conditions, GDNF covered the majority of the striatum. No behavioral abnormalities or weight loss were observed. Motor asymmetry resulting from unilateral GDNF treatment only appeared with a 2.5-fold higher vector and a 13-fold higher inducer doses. Our data suggest that using the herein-described inducible AAV vector, biological effects of GDNF can be obtained in response to sub-antimicrobial doxycycline doses.

  4. Downregulation of Proteinase-Activated Receptor-2, Interleukin-17, and Other Proinflammatory Genes by Subantimicrobial Doxycycline Dose in a Rat Periodontitis Model.

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    Castro, Myrella L; Franco, Gilson C N; Branco-de-Almeida, Luciana S; Anbinder, Ana L; Cogo-Müller, Karina; Cortelli, Sheila C; Duarte, Simone; Saxena, Deepak; Rosalen, Pedro L

    2016-02-01

    Subantimicrobial dose doxycycline (SDD) has been used as an adjunct in periodontal treatment because of its matrix metalloproteinase inhibition properties. Although the benefits of SDD therapy, such as improvement in the parameters of periodontal probing depth and clinical attachment level, have been proven in multiple clinical studies, the comprehension of other biologic mechanisms of action on periodontitis remains poorly investigated. Therefore, this animal-model study evaluated the effects of SDD monotherapy on the expressions of the following key proinflammatory genes: proteinase-activated receptor-2 (PAR2), tumor necrosis factor (TNF)-α, interleukin (IL)-17, and IL-1β. Male Wistar rats were assigned randomly to the following: 1) control group: no ligature-induced periodontitis and no treatment; 2) ligature group: ligature-induced periodontitis and placebo treatment; and 3) ligature + doxycycline group: ligature-induced periodontitis and SDD treatment. After the experimental time, animals were sacrificed, and reverse transcription-polymerase chain reaction was performed to analyze the mRNA expression of IL-1β, IL-17, TNF-α, and PAR2 in gingival tissue samples. Histologic analyses were performed on the furcation region and mesial gingiva of mandibular first molars to measure periodontal bone loss and collagen content. SDD administration significantly downregulated PAR2, IL-17, TNF-α, and IL-1β mRNA expressions (P <0.05). In addition, SDD treatment was accompanied by lower rates of alveolar bone loss (P <0.05) and maintenance of the amount of gingival collagen fibers. These findings reveal new perspectives regarding SDD efficacy because it can be partially related to proinflammatory gene expression modulation, even considering PAR2 and IL-17, which has not been investigated thus far.

  5. Long-term efficacy of subantimicrobial-dose doxycycline as an adjunctive treatment to scaling and root planing: a systematic review and meta-analysis.

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    Sgolastra, Fabrizio; Petrucci, Ambra; Gatto, Roberto; Giannoni, Mario; Monaco, Annalisa

    2011-11-01

    Subantimicrobial-dose doxycycline (SDD) is widely used as an adjunctive treatment to scaling and root planing (SRP), but its long-term effectiveness remains controversial. The purpose of this systematic review was to assess the actual evidence of the effectiveness of SRP + SDD compared to SRP + placebo in the treatment of chronic periodontitis. A literature search of electronic databases was performed for articles published through November 1, 2010. Several dental journals were screened during the manual search, and authors were contacted for missing information. The systematic review and meta-analysis were conducted according to the Quality of Reporting of Meta-Analyses statement and recommendations of the Cochrane Collaboration. The methodologic quality of the studies was determined via a Consolidated Standards of Reporting Trials-based assessment. Clinical attachment levels, probing depths, plaque and gingival indices, and gingival crevicular fluid levels were compared between baseline and the end of follow-up. Data were extracted and pooled using a random-effect model. The weighted mean difference was reported with the 95% confidence interval. Heterogeneity was assessed using the χ(2)-based Q-statistic method and I(2) measurement. P treatment designs, SDD dosage regimens (20 mg twice daily for 3 months), and post-treatment follow-up lengths (9 months). Significant differences were observed for all investigated clinical parameters in favor of the SRP + SDD group. The meta-analysis results seemed to support the long-term effectiveness of adjunctive SDD therapy; however, future studies are needed to confirm these findings.

  6. The effect of sub-antimicrobial dose-doxycycline periodontal therapy on serum inflammatory biomarker C-reactive protein levels in post-menopausal Women: A 2-year, double-blinded, randomized clinical trial

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    Rajesh S Koppikar

    2013-01-01

    Full Text Available Background: Periodontitis has been reported to be associated with coronary artery disease. Research is needed to determine whether therapies that improve periodontal health also reduce systemic marker of inflammation associated with both diseases. Aim: To determine whether sub-antimicrobial dose-doxycycline (SDD therapy can reduce systemic serum inflammatory biomarker C-reactive protein (CRP in post-menopausal women who have chronic periodontitis. Settings and Design: The study randomly assigned 128 eligible post-menopausal women with chronic periodontitis to a 90-day, twice-daily regimen of SDD or placebo tablets evaluated for 2 years, as an adjunct to periodontal maintenance therapy. Materials and Methods: The study assayed blood samples for inflammatory mediators at baseline, 1 year, and 2 years. CRP was measured using a high-sensitivity enzyme-linked immunosorbent assay. Results: SDD treatment reduced median high-sensitivity CRP by 18% (primary outcome = 0.02. Conclusion: Ninety-day SDD regimen in post-menopausal women significantly reduced the serum inflammatory biomarker CRP over a 2-year period.

  7. Effect of Azadirachta indica (Neem) and Aloe vera as compared to subantimicrobial dose doxycycline on matrix metalloproteinases (MMP)-2 and MMP-9: An in-vitro study

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    Kudalkar, Mithun D.; Nayak, Aarati; Bhat, Kishore S.; Nayak, Ranganath N.

    2014-01-01

    Background: A critical outcome of periodontal diseases is degradation of collagen in the periodontal tissues, by enzymes such as Matrix Metallo-Proteinases (MMPs). Doxycycline is known to down-regulate the activity of MMPs. Azadirachta indica (Neem) and Aloe vera are herbs known to have an anti-inflammatory effect. The present study was designed to evaluate the anti-inflammatory effect of Neem and Aloe vera by way of its inhibitory effect on MMP-2 and MMP-9 activity in cases of chronic periodontitis and compare it with doxcycline. Materials and Methods: A total of 30 subjects were enrolled in this study. Gingival tissue samples were obtained from patients diagnosed with the chronic periodontitis. The tissue extracts were treated with the said drug solutions and inhibition of MMP-2 and MMP-9 was analyzed. Enzymatic activity was detected by electrophoresis. The data was subjected to Student's paired t-test. Results: The results showed that the activity of MMP-2 and MMP-9 was significantly decreased by the use of doxycycline, Neem and Aloe vera. A 53.5% reduction in the MMP-2 and 52.5% reduction in the MMP-9 activity was seen when samples were subjected to Neem treatment at the concentration of 1500 μg/ml. Tissues treated with Aloe vera in the concentration of 2000 μg/ml showed a 20.09% reduction in the MMP-2 and 20.4% reduction in the MMP-9 activity. Doxycycline in the concentration of 300 μg/ml, showed an 82.1% reduction in the MMP-2 and 82.6% reduction in the MMP-9 activity. Conclusion: The present study demonstrated an inhibitory effect of Neem and Aloe vera on MMP-2 and MMP-9, which are involved in the extracellular matrix degradation during periodontitis. PMID:25364206

  8. A regulatable AAV vector mediating GDNF biological effects at clinically-approved sub-antimicrobial doxycycline doses

    NARCIS (Netherlands)

    Chtarto, Abdelwahed; Humbert-Claude, Marie; Bockstael, Olivier; Das, Atze T.; Boutry, Sébastien; Breger, Ludivine S.; Klaver, Bep; Melas, Catherine; Barroso-Chinea, Pedro; Gonzalez-Hernandez, Tomas; Muller, Robert N.; DeWitte, Olivier; Levivier, Marc; Lundberg, Cecilia; Berkhout, Ben; Tenenbaum, Liliane

    2016-01-01

    Preclinical and clinical data stress the importance of pharmacologically-controlling glial cell line-derived neurotrophic factor (GDNF) intracerebral administration to treat PD. The main challenge is finding a combination of a genetic switch and a drug which, when administered at a

  9. Anti-Inflammatory Properties of Low and High Doxycycline Doses: An In Vitro Study

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    Di Caprio, Roberta; Di Costanzo, Luisa; Monfrecola, Giuseppe

    2015-01-01

    Doxycycline is used to treat infective diseases because of its broadspectrum efficacy. High dose administration (100 or 200 mg/day) is often responsible for development of bacterial resistances and endogenous flora alterations, whereas low doses (20–40 mg/day) do not alter bacteria susceptibility to antibiotics and exert anti-inflammatory activities. In this study, we wanted to assess the efficacy of both low and high doxycycline doses in modulating IL-8, TNF-α, and IL-6 gene expression in HaCaT cells stimulated with LPS. Three experimental settings were used, differing in the timing of doxycycline treatment in respect to the insult induced by LPS: pretreatment, concomitant, and posttreatment. Low doses were more effective than high doses in modulating gene expression of LPS-induced proinflammatory cytokines (IL-8, TNF-α, and IL-6), when added before (pretreatment) or after (posttreatment) LPS stimulation. This effect was not appreciated when LPS and doxycycline were simultaneously added to cell cultures: in this case high doses were more effective. In conclusion, our in vitro study suggests that low doxycycline doses could be safely used in chronic or acute skin diseases in which the inflammatory process, either constantly in progress or periodically recurring, has to be prevented or controlled. PMID:25977597

  10. Doxycycline shows dose-dependent changes in hernia repair strength after mesh repair.

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    Tharappel, Job C; Harris, Jennifer W; Zwischenberger, Brittany A; Levy, Salomon M; Puleo, David A; Roth, J Scott

    2016-05-01

    Ventral hernia is a commonly occurring surgical problem. Our earlier studies have shown that a 30 mg/kg dose of doxycycline can significantly impact the strength of polypropylene (PP) mesh in a rat hernia repair model at 6 and 12 weeks. The objective of the present study was to investigate the dose dependence of doxycycline treatment on hernia repair strengths in rats. Fifty-six Sprague-Dawley rats underwent hernia repair with either PP mesh (n = 28) or sutures only (primary; n = 28); both groups were further divided into four doxycycline groups of seven animals each: control (0 mg/kg), low (3 mg/kg), medium (10 mg/kg), and high (30 mg/kg). One day before hernia repair surgery, animals received doxycycline doses by gavage and continued receiving daily until euthanasia. After 8 weeks, rats were euthanized and tissue samples from hernia repaired area were collected and analyzed for tensile strength using a tensiometer (Instron, Canton, MA, USA), while MMPs 2, 3, and 9, and collagen type 1 and 3 were analyzed by western blotting. In mesh-repaired animals, medium and high doxycycline dose repaired mesh fascia interface (MFI) showed significant increase in tensile strength when compared to control. In the primary repaired animals, there was no significant difference in MFI tensile strength in any dose group. In medium-dose MFI, there was a significant reduction in MMPs 2, 3, and 9. In this animal group, MFI showed significant increase in collagen 1 and significant reduction in collagen type 3 when compared to control. It is possible to improve the strength of mesh-repaired tissue by administering a significantly lower dose of the drug, which has implications for translation of the findings.

  11. Pilot study: digital subtraction radiography as a tool to assess alveolar bone changes in periodontitis patients under treatment with subantimicrobial doses of doxycycline

    NARCIS (Netherlands)

    Goren, A.D.; Dunn, S.M.; Wolff, M.; van der Stelt, P.F.; Colosi, D.C.; Golub, L.M.

    2008-01-01

    Background Subtle changes in marginal alveolar bone level can be demonstrated using digital subtraction of sequential radiographs. Objective We aimed to evaluate the practical application of geometrically corrected digital subtraction in a clinical study of alveolar bone response to a drug

  12. A randomized-controlled trial of low-dose doxycycline for periodontitis in smokers

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    Needleman, Ian; Suvan, Jean; Gilthorpe, Mark S.; Tucker, Richard; St George, Geoff; Giannobile, William; Tonetti, Maurizio; Jarvis, Martin

    2008-01-01

    Background/Aim Tobacco use reduces the effect of non-surgical periodontal therapy. Host-modulation with low-dose doxycycline (LDD) might favour repair and promote an improved treatment response. The aim of this study was to investigate the effect of LDD in smokers on non-surgical periodontal therapy. Material and Methods This was a parallel arm, randomized, identical placebo-controlled trial with masking of examiner, care-giver, participant and statistician and 6 months of follow-up. Patients received non-surgical therapy and 3 months of test or control drug. Statistical analysis used both conventional methods and multilevel modelling. Results Eighteen control and 16 test patients completed the study. The velocity of change was statistically greater for the test group for clinical attachment level −0.19 mm/month (95% CI= −0.34, 0.04; p=0.012) and probing depth 0.30 mm/month (95% CI= −0.42, −0.17; p < 0.001). However, no differences were observed for absolute change in clinical or biochemical markers at 6 months. Conclusions This study does not provide evidence of a benefit of using LDD as an adjunct to non-surgical periodontal therapy in smokers. PMID:17324155

  13. Doxycycline down-regulates matrix metalloproteinase expression and inhibits NF-κB signaling in LPS-induced PC3 cells.

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    Ogut, Deniz; Reel, Buket; Gonen Korkmaz, Ceren; Arun, Mehmet Zuhuri; Cilaker Micili, Serap; Ergur, Bekir Ugur

    2016-01-01

    Matrix metalloproteinase enzymes (MMPs) play important role in inflammation, malignant cell proliferation, invasion and angiogenesis by mediating extracellular matrix degradation. Doxycycline, a synthetic tetracycline, behaves as a MMP inhibitor at a subantimicrobial dose and inhibits tumor cell proliferation, invasion and angiogenesis. The aberrant activity of nuclear factor kappa B (NF-κB) causes activation of MMPs and thereby proliferation and invasion of cancer cells. The aim of this study was to investigate the effects of doxycycline on the expression of MMPs in lipopolysaccharide (LPS)-induced PC3 human prostate cancer cells and the possible role of NF-κB signaling. PC3 cells were incubated with LPS (0.5 μg/mL) for 24 h in the presence or absence of doxycycline (5 μg/mL). The effects of LPS and doxycycline on the expressions of MMP-2, MMP-8, MMP-9, MMP-10, NF-κB/p65, IκB-α, p-IκB-α, IKK-β were examined by Western blotting and immunohistochemistry in PC3 cells. Furthermore, relative proteinase activities of MMP-2 and MMP-9 were determined by gelatin zymography. LPS increased expression and activity of MMP-9 and expression of MMP-8, MMP-10, NF-κB /p65, p-IκB-α, IKK-β and doxycycline down-regulated its effects with the exception of MMP-10 expression. The expression of MMP-2 and IκB-α was affected by neither LPS nor doxycycline. Our findings indicate that doxycycline inhibits the expression of various MMPs and NF-κB signaling may play a role in the regulation of MMPs expression in LPS-induced PC3 human prostate cancer cells.

  14. Prospective open-label evaluation of long-term low-dose doxycycline for difficult-to-treat chronic rhinosinusitis with nasal polyps.

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    Pinto Bezerra Soter, A C; Bezerra, T F; Pezato, R; Teles Abdo, T R; Pilan, R M; Pinna, F R; Gevaert, P; van Zele, T; Bachert, C; Voegels, R L

    2017-06-01

    This study aimed to assess clinical outcomes of long-term low-dose oral doxycycline therapy in difficult-to-treat chronic rhinosinusitis with polyps (CRSwNP). This was a prospective, open-label study of 60 patients with difficult-to-treat CRSwNP who had undergone endoscopic sinus surgery. Patients were divided into two groups: 28 received nasal steroids, saline irrigation, and doxycycline (200 mg on the first day, followed by 100 mg once daily) for 12 weeks, while 30 received only nasal steroids and saline irrigation. The main outcome measure was an adequate effect size of doxycycline treatment on clinically meaningful significant improvement of SNOT-20. Other outcome measures were the SNOT-20, NOSE, and Lund-Kennedy scores. The following parameters were also analyzed: asthma, rhinitis, non-steroidal-exacerbated respiratory disease (NERD), and baseline serum IgG, IgA, IgE, IgM, ANCA, and eosinophil count. There was an adequate effect size of doxycycline treatment on clinically meaningful significant improvement of SNOT-20. Patients who received doxycycline also had significantly better outcomes regarding SNOT-20, NOSE, and Lund-Kennedy scores. There was a negative association among a clinically significant improvement of SNOT-20 and presence of asthma, NERD, and elevated serum IgE levels before treatment. These findings suggest that doxycycline may have a beneficial role for CRSwNP patients, especially for patients without asthma, NERD or high levels of serum IgE before treatment.

  15. Doxycycline-loaded nanotube-modified adhesives inhibit MMP in a dose-dependent fashion.

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    Palasuk, Jadesada; Windsor, L Jack; Platt, Jeffrey A; Lvov, Yuri; Geraldeli, Saulo; Bottino, Marco C

    2017-09-30

    This article evaluated the drug loading, release kinetics, and matrix metalloproteinase (MMP) inhibition of doxycycline (DOX) released from DOX-loaded nanotube-modified adhesives. DOX was chosen as the model drug, since it is the only MMP inhibitor approved by the U.S. Food and Drug Administration. Drug loading into the nanotubes was accomplished using DOX solution at distinct concentrations. Increased concentrations of DOX significantly improved the amount of loaded DOX. The modified adhesives were fabricated by incorporating DOX-loaded nanotubes into the adhesive resin of a commercial product. The degree of conversion (DC), Knoop microhardness, DOX release kinetics, antimicrobial, cytocompatibility, and anti-MMP activity of the modified adhesives were investigated. Incorporation of DOX-loaded nanotubes did not compromise DC, Knoop microhardness, or cell compatibility. Higher concentrations of DOX led to an increase in DOX release in a concentration-dependent manner from the modified adhesives. DOX released from the modified adhesives did not inhibit the growth of caries-related bacteria, but more importantly, it did inhibit MMP-1 activity. The loading of DOX into the nanotube-modified adhesives did not compromise the physicochemical properties of the adhesives and the released levels of DOX were able to inhibit MMP activity without cytotoxicity. Doxycycline released from the nanotube-modified adhesives inhibited MMP activity in a concentration-dependent fashion. Therefore, the proposed nanotube-modified adhesive may hold clinical potential as a strategy to preserve resin/dentin bond stability.

  16. A randomized, phase 2, dose-ranging study in the treatment of moderate to severe inflammatory facial acne vulgaris with doxycycline calcium.

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    Leyden, James J; Bruce, Suzanne; Lee, Chai Sue; Ling, Mark; Sheth, Pranav B; Stewart, Daniel M; Werschler, William P; Gilbert, Richard D; Kircik, Leon

    2013-06-01

    Doxycycline calcium (WC2055) is a drug substance with a possible role in the treatment of acne. The objective of this study was to evaluate the safety and efficacy of three doses of doxycycline calcium tablets compared with placebo in the treatment of moderate to severe inflammatory facial acne vulgaris. This was a randomized, double-blind, phase 2 dose-ranging study in subjects with moderate to severe inflammatory acne aged 12 years to 45 years. Subjects were randomized to receive doxycycline calcium tablets 0.6, 1.2, or 2.4 mg/kg/day or placebo, and instructed to take their tablets once daily for 12 weeks, in the evening at least 1 hour before or 2 hours after mealtime. The primary efficacy variables were the dichotomized Investigator's Global Assessment score (success or failure) at week 12 (success defined as ≥ 2 score decrease from baseline) and the absolute change from baseline to week 12 in inflammatory lesion count. A dose-response effect was seen with doxycycline calcium formulation in subjects with moderate to severe inflammatory acne. The highest dose-group (corresponding to approximately 2.4 mg/kg/day) showed a statistically significant difference from placebo. The dose-response effect was confirmed by logistic regression analysis for both treatment success and incidence of gastrointestinal adverse events. A limitation of this study is that safety and efficacy were only studied on moderate to severe inflammatory acne. Also, the study was not prospectively powered to show efficacy differences. Doxycycline calcium shows a dose-response effect in reducing inflammatory lesions in subjects with moderate to severe inflammatory acne.

  17. The effect of adjunctive low-dose doxycycline and licorice therapy on gingival crevicular fluid matrix metalloproteinase-8 levels in chronic periodontitis

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    Shirin Zahra Farhad

    2013-01-01

    Full Text Available Background: This study compared the effect of adjunctive low dose doxycycline and licorice on gingival crevicular fluid (GCF matrix metalloproteinase-8 (MMP-8 levels in patients with chronic periodontitis. Materials and Methods: In this in vivo, experimental study 39 patients with mild to moderate chronic periodontitis were selected. Samples of GCF were collected from three deepest pockets and MMP-8 concentration was measured. Patients were divided into three groups (n = 13. Groups were treated with doxycycline, licorice and placebo. Sampling and measurement of MMP-8 was repeated after 6 weeks. Data was analyzed by t-paired and ANOVA test. P < 0.001 was considered significant. Results: The decrease in mean of MMP-8 concentration was higher in doxycycline and licorice group in comparison with the placebo group and the difference was statistically significant (P value < 0.001. The decrease in mean of MMP-8 concentration was higher in licorice group than doxycycline group, but the difference was not statistically significant. Conclusion: The present study showed that licorice extract can prevent the production of MMPs by host cells and can be as useful as antibiotics like doxycycline to cure periodontal and other inflammatory diseases. It must be added that no side-effects were observed in usage of licorice extract.

  18. Doxycycline Injection

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    ... may have been exposed to anthrax in the air. Doxycycline injection is in a class of medications ... decrease the effectiveness of hormonal contraceptives (birth control pills, patches, rings, or injections). Talk to your doctor ...

  19. Influence of subsalicylate bismuth on absorption of doxycycline.

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    Ericsson, C D; Feldman, S; Pickering, L K; Cleary, T G

    1982-04-23

    The influence of a typical 60-mL dose of subsalicylate bismuth (Pepto-Bismol) on the absorption of 200 mg of orally administered doxycycline hyclate was studied. Bioavailability of doxycycline was significantly reduced by 37% and 51%, respectively, when subsalicylate bismuth was given simultaneously and as a multiple-dose regimen before doxycycline. Peak serum concentrations of doxycycline were significantly decreased when subsalicylate bismuth was given two hours before doxycycline but not when given two hours after doxycycline. Subsalicylate bismuth should not be taken when doxycycline is used for therapeutic purposes, and we suggest travelers should not take the agents together in an effort to prevent diarrhea.

  20. Triple therapy with high-dose proton-pump inhibitor, amoxicillin, and doxycycline is useless for Helicobacter pylori eradication: a proof-of-concept study.

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    Almeida, Nuno; Romãozinho, José M; Donato, Maria M; Luxo, Cristina; Cardoso, Olga; Cipriano, Maria A; Marinho, Carol; Sofia, Carlos

    2014-04-01

    Helicobacter pylori resistance to antibiotics is steadily increasing and multidrug-resistant strains are common and difficult to eliminate, mainly in countries where bismuth, tetracycline, furazolidone, and rifabutin are unavailable. To evaluate the efficacy and safety of a triple therapy with proton-pump inhibitor (PPI), amoxicillin, and doxycycline in patients with multidrug-resistant H. pylori. This prospective study involved 16 patients (13 females; mean age - 50 ± 11.3 years) infected by H. pylori with known resistance to clarithromycin, metronidazole, and levofloxacin, but susceptibility to amoxicillin and tetracycline. All patients were previously submitted to upper endoscopy with gastric biopsies for H. pylori culture and susceptibility testing by Etest. Mutations in 23S rRNA and gyrA genes were determined by real-time PCR. A 10-day eradication regimen with PPI (double-standard dose b.i.d.), amoxicillin (1000 mg b.i.d.), and doxycycline (100 mg b.i.d.) was prescribed after pretreatment with PPI during 3 days. Eradication success was assessed by (13) C-urea breath test 6-10 weeks after treatment. Compliance and adverse events were determined through phone contact immediately after treatment and specific written questionnaires. Only one patient did not complete treatment due to adverse events. Another four patients experienced mild side effects not affecting compliance. The control (13) C-urea breath test was positive in all patients. Per-protocol and intention-to-treat eradication rates were 0%. Although safe, a triple-therapy protocol with high-dose PPI, amoxicillin, and doxycycline is useless for multidrug-resistant H. pylori eradication. © 2014 John Wiley & Sons Ltd.

  1. Comparison of a single-dose vectored thermal pulsation procedure with a 3-month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction

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    Hagen KB

    2018-01-01

    Full Text Available Kerry B Hagen,1 Raman Bedi,2 Caroline A Blackie,3 Kellie J Christenson-Akagi1 1EyeHealth Northwest, Portland, OR, USA; 2Iris Advanced Eye Centre, Chandigarh, India; 3TearScience, Inc., Morrisville, NC, USA Purpose: The aim of this study was to compare the efficacy of a single bilateral 12-minute vectored thermal pulsation (VTP procedure versus daily oral doxycycline for 3 months for moderate-to-severe meibomian gland dysfunction (MGD.Methods: This prospective, randomized, parallel-group, single-masked study included 28 subjects who received either a single-dose VTP or 3 months of doxycycline treatment. At baseline and 3 months post treatment, all subjects were evaluated for the following: dry eye symptoms with a standard dry eye questionnaire (the Standard Patient Evaluation for Eye Dryness [SPEED], meibomian gland (MG function by counting the number of glands yielding liquid secretion with the MG evaluator (MGE, tear breakup time (TBUT and corneal and conjunctival staining.Results: In the VTP group, at 3 months, there was a significant improvement in MG function (4.00±1.47 to 7.73±5.53, SPEED score (11.00±3.30 to 5.42±2.15, TBUT (6.26±2.01 to 8.44±1.81, corneal staining (0.38±0.50 to 0.12±0.33 and conjunctival staining (1.69±1.93 to 0.62±0.85. In the doxycycline group, there was a significant improvement in MG function (4.63±1.41 to 10.63±5.91, SPEED score (13.42±4.17 to 9.42±5.47 and conjunctival staining (2.38±1.88 to 1.13±1.51, but the improvement in TBUT (6.90±2.56 to 7.59±2.03 and corneal staining (0.21±0.41 to 0.13±0.34 was not statistically significant (p=0.262 and p=0.414, respectively. At 3 months, SPEED score was significantly better in the VTP group (p<0.05; other parameters were comparable between the two groups.Conclusion: A single 12-minute bilateral VTP procedure was significantly more effective than the 3-month daily course of oral doxycycline at improving the dry eye symptoms secondary to MGD. A single

  2. Effectiveness of low-dose doxycycline (LDD on clinical symptoms of Sjögren's Syndrome: a randomized, double-blind, placebo controlled cross-over study

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    Vuotila Tuija

    2007-12-01

    Full Text Available Abstract Background Matrix metalloproteinases (MMPs are proteolytic enzymes that may contribute to tissue destruction in Sjögren's syndrome (SS. Low-dose doxycycline (LDD inhibits MMPs. We evaluated the efficacy of LDD for the subjective symptoms in primary SS patients. This was a randomized, double blind, placebo controlled cross-over study. 22 patients were randomly assigned to receive either 20 mg LDD or matching placebo twice a day for 10 weeks. The first medication period was followed by 10-week washout period, after which the patient received either LDD or placebo, depending on the first drug received, followed by the second washout period. Stimulated saliva flow rates and pH were measured before and after one and ten weeks of each medication and after washout periods. VAS scale was used to assess the effect of LDD and placebo on following six subjective symptoms: xerostomia; xerophtalmia; difficulty of swallowing; myalgia; arthralgia; and fatigue. The effect was evaluated for each medication and washout period separately. Results Overall, the effects of medications on subjective symptoms were minor. Wilcoxon test demonstrated increased fatigue with LDD during medication (p Conclusion LDD may not be useful in reducing the primary SS symptoms.

  3. Cutaneous hyperpigmentation induced by doxycycline: a case series

    NARCIS (Netherlands)

    Keijmel, S.P.; Kasteren, M.E.E. van; Blokx, W.A.M.; Meer, J.W.M. van der; Rossum, M.M. van; Bleeker-Rovers, C.P.

    2015-01-01

    Cutaneous hyperpigmentation is a well-known side effect of tetracyclines, but doxycycline-induced cutaneous hyperpigmentation has only been described in one patient with a therapeutic dosage of doxycycline, and in one patient using suprapharmacological doses. We describe four patients with cutaneous

  4. Fixed-Dose Combination Gel of Adapalene and Benzoyl Peroxide plus Doxycycline 100 mg versus Oral Isotretinoin for the Treatment of Severe Acne: Efficacy and Cost Analysis.

    Science.gov (United States)

    Penna, Pete; Meckfessel, Matthew H; Preston, Norman

    2014-01-01

    Acne vulgaris is a chronic skin disease with a high prevalence. Left untreated or inadequately treated, acne vulgaris can lead to psychological and physical scarring, as well as to unnecessary medical expenses. Oral isotretinoin is an effective treatment for severe resistant nodular and conglobate acne vulgaris. A regimen consisting of a fixed-dose combination of adapalene and benzoyl peroxide gel, 0.1%/2.5% (A-BPO) with oral doxycycline 100 mg (A-BPO/D) has been demonstrated to be efficacious and well tolerated in patients with severe acne and may be an alternative to oral isotretinoin for some patients with severe acne. The objective of this analysis was to compare the relative efficacy and associated costs of A-BPO/D versus oral isotretinoin. In this analysis, comparisons of relative efficacy were made using previously published studies involving similar patient populations with severe acne that warrant the use of oral isotretinoin. The pricing for oral doxycycline and oral isotretinoin was estimated based on the maximum allowable cost from 9 states, and the pricing for A-BPO was calculated as the range between the average wholesale price and the wholesale acquisition cost. For this analysis, 2 treatment models were generated to compare costs: (1) a basic treatment model that examined the costs of an initial regimen of either A-BPO/D or oral isotretinoin without considering probable outcomes, and (2) a long-term model that factored in likely treatment outcomes and subsequent treatments into associated costs. The basic treatment model assumed that patients would be prescribed a single regimen of A-BPO/D for 12 weeks or oral isotretinoin for 20 weeks. The long-term model considered the probability of each treatment successfully managing patients' acne, as well as likely additional regimens of A-BPO monotherapy or an additional regimen of oral isotretinoin. As a result of different treatment durations, the costs for each treatment were normalized to weekly cost of

  5. Doxycycline and suicidality

    National Research Council Canada - National Science Library

    Atigari, Onome Victor; Hogan, Carys; Healy, David

    2013-01-01

    A case series outlining three young individuals with no history of mental disorder who were treated for skin conditions with doxycycline, but developed suicidal ideation with an outcome of suicide in two of the cases...

  6. Doxycycline and Benznidazole Reduce the Profile of Th1, Th2, and Th17 Chemokines and Chemokine Receptors in Cardiac Tissue from Chronic Trypanosoma cruzi-Infected Dogs

    Directory of Open Access Journals (Sweden)

    Guilherme de Paula Costa

    2016-01-01

    Full Text Available Chemokines (CKs and chemokine receptors (CKR promote leukocyte recruitment into cardiac tissue infected by the Trypanosoma cruzi. This study investigated the long-term treatment with subantimicrobial doses of doxycycline (Dox in association, or not, with benznidazole (Bz on the expression of CK and CKR in cardiac tissue. Thirty mongrel dogs were infected, or not, with the Berenice-78 strain of T. cruzi and grouped according their treatments: (i two months after infection, Dox (50 mg/kg 2x/day for 12 months; (ii nine months after infection, Bz (3,5 mg/kg 2x/day for 60 days; (iii Dox + Bz; and (iv vehicle. After 14 months of infection, hearts were excised and processed for qPCR analysis of Th1 (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL11, Th2 (CCL1, CCL17, CCL24, and CCL26, Th17 (CCL20 CKs, Th1 (CCR5, CCR6, and CXCR3, and Th2/Th17 (CCR3, CCR4, and CCR8 CKR, as well as IL-17. T. cruzi infection increases CCL1, CCL2, CCL4, CCL5, CCL17, CXCL10, and CCR5 expression in the heart. Dox, Bz, or Dox + Bz treatments cause a reversal of CK and CKR and reduce the expression of CCL20, IL-17, CCR6, and CXCR3. Our data reveal an immune modulatory effect of Dox with Bz, during the chronic phase of infection suggesting a promising therapy for cardiac protection.

  7. Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data.

    Science.gov (United States)

    Hopkins, Ashley M; Wojciechowski, Jessica; Abuhelwa, Ahmad Y; Mudge, Stuart; Upton, Richard N; Foster, David J R

    2017-03-01

    The literature presently lacks a population pharmacokinetic analysis of doxycycline. This study aimed to develop a population pharmacokinetic model of doxycycline plasma concentrations that could be used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC. Doxycycline pharmacokinetic data were available from eight phase 1 clinical trials following single/multiple doses of conventional-release doxycycline capsules, Doryx delayed-release tablets, and Doryx MPC under fed and fasted conditions. A population pharmacokinetic model was developed in a stepwise manner using NONMEM, version 7.3. The final covariate model was developed according to a forward inclusion (P doxycycline plasma concentrations following oral doxycycline administration. The model was used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC, and it could potentially be used to critically examine and optimize doxycycline dose regimens. Copyright © 2017 American Society for Microbiology.

  8. Targeting matrix metalloproteinases with intravenous doxycycline in severe sepsis--A randomised placebo-controlled pilot trial.

    Science.gov (United States)

    Nukarinen, Eija; Tervahartiala, Taina; Valkonen, Miia; Hynninen, Marja; Kolho, Elina; Pettilä, Ville; Sorsa, Timo; Backman, Janne; Hästbacka, Johanna

    2015-09-01

    An overwhelming inflammatory process is the hallmark of severe sepsis and septic shock. Matrix metalloproteinases (MMPs)-8 and -9 are released from neutrophils and activated in sepsis to participate in inflammation in several ways. High levels of MMP-8 may associate with increased ICU mortality. The activity of MMP-8 and -9 is regulated by a natural inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1). Moreover, MMPs are chemically inhibited by tetracycline-group antibiotics, such as doxycycline. We therefore aimed to study plasma concentration and MMP inhibition after intravenous doxycycline in critically ill patients with severe sepsis and septic shock in a prospective, randomised, placebo-controlled double-blinded pilot trial. Twenty-four patients with severe sepsis or septic shock were randomised in 3 groups. Group 1 received 200, 100 and 100mg, group 2 100, 50 and 50mg of intravenous doxycycline and group 3 placebo on three consecutive days. We measured doxycycline concentrations from baseline up to day 5. MMPs and TIMP-1 concentrations were measured from baseline up to day 10 of study and we compared their changes over time from baseline to 72 h and from baseline to 120 h. Data from 23 patients were analysed. At 72 h all patients in group 1 showed doxycycline concentrations >1 mg/l, whereas none in group 2 did. No serious adverse effects of the drug were recorded. We observed no differences over time up to 72 or up to 120 h in the concentrations or activities of MMP-8, -9 or TIMP-1 in any of the groups. We found intravenous doxycycline 100, 50 and 50mg to be adequate to achieve a sub-antimicrobial concentration in patients with severe sepsis or septic shock but having no impact on MMP-8, -9 or TIMP-1 concentrations or activities. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. 21 CFR 522.778 - Doxycycline hyclate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Doxycycline hyclate. 522.778 Section 522.778 Food... Doxycycline hyclate. (a) Specifications. Doxycycline hyclate solution contains 8.5 percent doxycycline activity. A syringe of N-methyl-2-pyrrolidone and poly (DL-lactide) mixed with a syringe of doxycycline...

  10. Esophagitis Induced by Doxycycline Treatment

    Directory of Open Access Journals (Sweden)

    Engin Şenel

    2016-09-01

    Full Text Available Esophagitis is the most common disease of the esophagus. Drug use is one of the reasons of chemical esophagitis. Herein, we report two male patients of 17 and 18 years of age who developed esophagitis in acne treatment with doxycycline. Both patients took doxycycline capsules for approximately one week. Ulcerations were detected at upper and mid-esophagus of the 17-year-old patient. Circular ulcerations were found at mid-esophagus of the 18-year-old case. Doxycycline induced esophagitis is a preventable disease with the physician giving appropriate medication ingestion advice to the patient.

  11. The effect of doxycycline treatment on the postvaccinal immune response in pigs

    Energy Technology Data Exchange (ETDEWEB)

    Pomorska-Mól, Małgorzata, E-mail: mpomorska@piwet.pulawy.pl; Kwit, Krzysztof; Markowska-Daniel, Iwona; Pejsak, Zygmunt

    2014-07-01

    The effect of a seven-day antibiotic therapy with doxycycline was investigated on the postvaccinal humoral and cellular immune response in pigs. The selected parameters of non-specific immunity were also studied. Fifty pigs were used (control not vaccinated (C, n = 10), control vaccinated (CV, n = 20), and experimental — received doxycycline (DOXY, n = 20)). For vaccination live-attenuated vaccine against pseudorabies (PR) was used. From day − 1 to day 5 pigs from DOXY group received doxycycline orally with drinking water, at the recommended dose. Pigs from DOXY and CV groups were vaccinated at 8 and 10 weeks of age. The results of the present study showed that cell-mediated postvaccinal immune response can be modulated by oral treatment with doxycycline. Significantly lower values of stimulation index were observed after PRV restimulation in doxycycline-treated pigs. Moreover, in the DOXY group a significant decrease in IFN-γ production after PRV restimulation was noted. The significantly lower number of CD4+CD8 + cells was also observed in doxy-treated, vaccinated pigs, 2 weeks after final vaccination. Simultaneously, specific humoral response was not disturbed. This study demonstrated the importance of defining the immune modulatory activity of doxycycline because it may alter the immune responses to vaccines. The exact mechanism of T-cell response suppression by doxycycline remains to be elucidated, however the influence of doxycycline on the secretion of various cytokines, including IFN-γ, may be considered as a possible cause. The present observations should prompt further studies on the practical significance of such phenomena in terms of clinical implications. - Highlights: • We examine the postvaccinal immune response in pigs treated with doxycycline. • Doxycycline negatively influenced the specific proliferation after recall stimulation. • Doxycycline negatively influenced secretion of IFN-γ after recall stimulation. • The lower number of

  12. Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases

    Science.gov (United States)

    Walker, Naomi F.; Clark, Simon O.; Oni, Tolu; Andreu, Nuria; Tezera, Liku; Singh, Shivani; Saraiva, Luísa; Pedersen, Bernadette; Kelly, Dominic L.; Tree, Julia A.; D'Armiento, Jeanine M.; Meintjes, Graeme; Mauri, Francesco A.; Williams, Ann; Wilkinson, Robert J.; Friedland, Jon S.

    2012-01-01

    Rationale: Tuberculosis kills more than 1.5 million people per year, and standard treatment has remained unchanged for more than 30 years. Tuberculosis (TB) drives matrix metalloproteinase (MMP) activity to cause immunopathology. In advanced HIV infection, tissue destruction is reduced, but underlying mechanisms are poorly defined and no current antituberculous therapy reduces host tissue damage. Objectives: To investigate MMP activity in patients with TB with and without HIV coinfection and to determine the potential of doxycycline to inhibit MMPs and decrease pathology. Methods: Concentrations of MMPs and cytokines were analyzed by Luminex array in a prospectively recruited cohort of patients. Modulation of MMP secretion and Mycobacterium tuberculosis growth by doxycycline was studied in primary human cells and TB-infected guinea pigs. Measurements and Main Results: HIV coinfection decreased MMP concentrations in induced sputum of patients with TB. MMPs correlated with clinical markers of tissue damage, further implicating dysregulated protease activity in TB-driven pathology. In contrast, cytokine concentrations were no different. Doxycycline, a licensed MMP inhibitor, suppressed TB-dependent MMP-1 and -9 secretion from primary human macrophages and epithelial cells by inhibiting promoter activation. In the guinea pig model, doxycycline reduced lung TB colony forming units after 8 weeks in a dose-dependent manner compared with untreated animals, and in vitro doxycycline inhibited mycobacterial proliferation. Conclusions: HIV coinfection in patients with TB reduces concentrations of immunopathogenic MMPs. Doxycycline decreases MMP activity in a cellular model and suppresses mycobacterial growth in vitro and in guinea pigs. Adjunctive doxycycline therapy may reduce morbidity and mortality in TB. PMID:22345579

  13. Comparison of Doxycycline and Benzathine Penicillin G for the Treatment of Early Syphilis.

    Science.gov (United States)

    Xiao, Hailu; Liu, Dianchang; Li, Zhen; Zheng, Rongtao; Li, Zhongwei; Hou, Jianling; Zhang, Shengjia; Chu, Tongsheng; Tian, Hongqing; Zhang, Furen

    2017-07-01

    Doxycycline is the preferred recommended second-line treatment for the treatment of early syphilis. Recent reports showed a declining efficacy trend of doxycycline in treatment of early syphilis. The aim of our study was to assess the serological response to the treatment for early syphilis with doxycycline compared with benzathine penicillin G and evaluate whether doxycycline is still an effective agent for the treatment of early syphilis. A record-based retrospective study was conducted. Patients were diagnosed with early syphilis in an sexually transmitted disease (STD) clinic from January 1, 2008 to December 31, 2014. They were treated with a single dose of benzathine penicillin G 2.4MU or oral doxycycline 100 mg twice daily for 14 days. Pearson's chi-squared test was used for data analysis. 601 cases were included in the final study sample: 105 (17.5%) patients received a 14-day course of doxycycline (doxycycline group), and 496 (82.5%) patients received single-dose benzathine penicillin G (BPG group). The serological responses at 6 months and 12 months after treatment were compared. No statistically significant differences were found between the two groups at 6 months (69.52% vs. 75.00%, P=0.245), and at 12 months (92.38% vs. 96.17%, P=0.115). Doxycycline is still an effective agent for the treatment of early syphilis.

  14. Doxycycline induced Esophagitis

    Directory of Open Access Journals (Sweden)

    Banu Karakus Yilmaz

    2014-02-01

    Full Text Available Esophagitis is a hazardous condition such as acid reflux of esophageal mucosa, infection, systemic diseases, radiation, drugs and trauma. Drug- induced esophagial injury (DIEI is a disease with the use of variety of drugs that caused serious damage and ulcer in the mucosa of the esophagus. The most commonly implicated drugs are non-steroidal anti-inflammatory drugs (NSAIDs, chloride and especially antibiotics. Thirty-six year-old female patient presented to the emergency department with odynophagia during swallowing and complaining of retrosternal pain. One week before 100 mg doxycycline (2x1 PO for therapeutic abortion were prescribed. It was learned that in the third day of the initiation of medication, the patient\\'s symptoms began and stopped using drug by the fourth day due to advers effect of drugs, but her symptoms didn’t regressed although she didn’t use them. Endoscopy appointment was taken, proton pump inhibitor and antiacid treatment was given, than patient was discharged from the emergency department. In the endoscopy, 20 mm segment esophageal ulcer was seen approximately in the 30.th cm of the esophagius. DIEI is a relatively common, although under-recognized, so this case was presented for remainding DIEI to emergency medicine personals and reweiving its diagnosis, treatment and follow-up.

  15. Doxycycline does not influence established abdominal aortic aneurysms in angiotensin II-infused mice.

    Directory of Open Access Journals (Sweden)

    Xiaojie Xie

    Full Text Available There is no proven medical approach to attenuating expansion and rupture of abdominal aortic aneurysms (AAAs. One approach that is currently being investigated is the use of doxycycline. Despite being primarily used as an antimicrobial drug, doxycycline has been proposed to function in reducing AAA expansion. Doxycycline is effective in reducing the formation in the most commonly used mouse models of AAAs when administered prior to the initiation of the disease. The purpose of the current study was to determine the effects of doxycycline on established AAAs when it was administered at a dose that produces therapeutic serum concentrations.LDL receptor -/- male mice fed a saturated-fat supplemented diet were infused with AngII (1,000 ng/kg/min via mini-osmotic pumps for 28 days. Upon verification of AAA formation by noninvasive high frequency ultrasonography, mice were stratified based on aortic lumen diameters, and continuously infused with AngII while also administered either vehicle or doxycycline (100 mg/kg/day in drinking water for 56 days. Administration of doxycycline led to serum drug concentrations of 2.3 ± 0.6 µg/ml. Doxycycline administration had no effect on serum cholesterol concentrations and systolic blood pressures. Doxycycline administration did not prevent progressive aortic dilation as determined by temporal measurements of lumen dimensions using high frequency ultrasound. This lack of effect on AAA regression and progression was confirmed at the termination of the study by ex vivo measurements of maximal width of suprarenal aortas and AAA volumes. Also, doxycycline did not reduce AAA rupture. Medial and adventitial remodeling was not overtly changed by doxycycline as determined by immunostaining and histological staining.Doxycycline administration did not influence AngII-induced AAA progression and aortic rupture when administered to mice with established AAAs.

  16. Doxycycline Does Not Influence Established Abdominal Aortic Aneurysms in Angiotensin II-Infused Mice

    Science.gov (United States)

    Xie, Xiaojie; Lu, Hong; Moorleghen, Jessica J.; Howatt, Deborah A.; Rateri, Debra L.; Cassis, Lisa A.; Daugherty, Alan

    2012-01-01

    Background There is no proven medical approach to attenuating expansion and rupture of abdominal aortic aneurysms (AAAs). One approach that is currently being investigated is the use of doxycycline. Despite being primarily used as an antimicrobial drug, doxycycline has been proposed to function in reducing AAA expansion. Doxycycline is effective in reducing the formation in the most commonly used mouse models of AAAs when administered prior to the initiation of the disease. The purpose of the current study was to determine the effects of doxycycline on established AAAs when it was administered at a dose that produces therapeutic serum concentrations. Methods and Results LDL receptor −/− male mice fed a saturated-fat supplemented diet were infused with AngII (1,000 ng/kg/min) via mini-osmotic pumps for 28 days. Upon verification of AAA formation by noninvasive high frequency ultrasonography, mice were stratified based on aortic lumen diameters, and continuously infused with AngII while also administered either vehicle or doxycycline (100 mg/kg/day) in drinking water for 56 days. Administration of doxycycline led to serum drug concentrations of 2.3±0.6 µg/ml. Doxycycline administration had no effect on serum cholesterol concentrations and systolic blood pressures. Doxycycline administration did not prevent progressive aortic dilation as determined by temporal measurements of lumen dimensions using high frequency ultrasound. This lack of effect on AAA regression and progression was confirmed at the termination of the study by ex vivo measurements of maximal width of suprarenal aortas and AAA volumes. Also, doxycycline did not reduce AAA rupture. Medial and adventitial remodeling was not overtly changed by doxycycline as determined by immunostaining and histological staining. Conclusions Doxycycline administration did not influence AngII-induced AAA progression and aortic rupture when administered to mice with established AAAs. PMID:23029514

  17. Treatment efficacy of azithromycin 1 g single dose versus doxycycline 100 mg twice daily for 7 days for the treatment of rectal chlamydia among men who have sex with men - a double-blind randomised controlled trial protocol.

    Science.gov (United States)

    Lau, Andrew; Kong, Fabian; Fairley, Christopher K; Donovan, Basil; Chen, Marcus; Bradshaw, Catriona; Boyd, Mark; Amin, Janaki; Timms, Peter; Tabrizi, Sepehr; Regan, David G; Lewis, David A; McNulty, Anna; Hocking, Jane S

    2017-01-06

    Rectal infection with Chlamydia trachomatis is one of the most common bacterial sexually transmissible infections among men who have sex with men (MSM) with diagnosis rates continuing to rise. Current treatment guidelines recommend either azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days. However, there are increasing concerns about treatment failure with azithromycin. We are conducting the first randomised controlled trial (RCT) to compare treatment efficacy of azithromycin versus doxycycline for the treatment of rectal chlamydia in MSM. The Rectal Treatment Study will recruit 700 MSM attending Australian sexual health clinics for the treatment of rectal chlamydia. Participants will be asked to provide rectal swabs and will be randomised to either azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days. Participants will be asked to complete questionnaires about adverse drug reactions, sexual behaviour and drug adherence via short message service and online survey. The primary outcome is the treatment efficacy as determined by a negative chlamydia nucleic acid amplification test at 4 weeks post treatment. Secondary outcomes will utilise whole genome sequencing and mRNA assay to differentiate between treatment failure, reinfection or false positive results. Rectal chlamydia is an increasing public health concern as use of pre-exposure prophylaxis against HIV becomes commonplace. Optimal, evidence-based treatment is critical to halting ongoing transmission. This study will provide the first RCT evidence comparing azithromycin and doxycycline for the treatment of rectal chlamydia. The results of this trial will establish which treatment is more efficacious and inform international management guidelines. Australian New Zealand Clinical Trials Registry ACTRN12614001125617.

  18. Doxycycline Indirectly Inhibits Proteolytic Activation of Tryptic Kallikrein-Related Peptidases and Activation of Cathelicidin

    Science.gov (United States)

    Kanada, Kimberly N.; Nakatsuji, Teruaki; Gallo, Richard L.

    2014-01-01

    The increased abundance and activity of cathelicidin and kallikrein 5 (KLK5), a predominant trypsin-like serine protease (TLSP) in the stratum corneum, have been implicated in the pathogenesis of rosacea, a disorder treated by the use of low-dose doxycycline. Here we hypothesized that doxycycline can inhibit activation of tryptic KLKs through an indirect mechanism by inhibition of matrix metalloproteinases (MMPs) in keratinocytes. The capacity of doxycycline to directly inhibit enzyme activity was measured in surface collections of human facial skin and extracts of cultured keratinocytes by fluorescence polarization assay against fluorogenic substrates specific for MMPs or TLSPs. Doxycycline did inhibit MMP activity but did not directly inhibit serine protease activity against a fluorogenic substrate specific for TLSPs. However, when doxycycline or other MMP inhibitors were added to live keratinocytes during the production of tryptic KLKs, this treatment indirectly resulted in decreased TLSP activity. Furthermore, doxycycline under these conditions inhibited the generation of the cathelicidin peptide LL-37 from its precursor protein hCAP18, a process dependent on KLK activity. These results demonstrate that doxycycline can prevent cathelicidin activation, and suggest a previously unknown mechanism of action for doxycycline through inhibiting generation of active cathelicidin peptides. PMID:22336948

  19. Doxycycline-induced gastrointestinal injury.

    Science.gov (United States)

    Affolter, Kajsa; Samowitz, Wade; Boynton, Kathleen; Kelly, Erinn Downs

    2017-08-01

    Doxycycline-induced gastric injury is a rarely recognized adverse effect of a common medication. Only 2 cases have previously described the distinctive capillary degeneration identified in gastric mucosa. We expanded on this by describing additional involved sites, endoscopic findings, and patient characteristics. Gastrointestinal biopsy materials for cases indexed with the word doxycycline were retrieved and the histology reviewed. The medical record was used to obtain clinical details. Three cases with biopsy materials were identified from the search, and doxycycline ingestion was confirmed. All patients' gastric biopsies had small vessel injury with fibrinoid material around the vessel, and 1 patient had similar changes in the duodenum. Endoscopic findings included fundic and pyloric erosions and ulcers. One patient had a normal endoscopy on follow-up after drug cessation. Confirmation and increased understanding of this drug-specific injury pattern are important for patient management, as cessation appears to result in symptom improvement and healing. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Doxycycline-encapsulated nanotube-modified dentin adhesives.

    Science.gov (United States)

    Feitosa, S A; Palasuk, J; Kamocki, K; Geraldeli, S; Gregory, R L; Platt, J A; Windsor, L J; Bottino, M C

    2014-12-01

    This article presents details of fabrication, biological activity (i.e., anti-matrix metalloproteinase [anti-MMP] inhibition), cytocompatibility, and bonding characteristics to dentin of a unique doxycycline (DOX)-encapsulated halloysite nanotube (HNT)-modified adhesive. We tested the hypothesis that the release of DOX from the DOX-encapsulated nanotube-modified adhesive can effectively inhibit MMP activity. We incorporated nanotubes, encapsulated or not with DOX, into the adhesive resin of a commercially available bonding system (Scotchbond Multi-Purpose [SBMP]). The following groups were tested: unmodified SBMP (control), SBMP with nanotubes (HNT), and DOX-encapsulated nanotube-modified adhesive (HNT+DOX). Changes in degree of conversion (DC) and microtensile bond strength were evaluated. Cytotoxicity was examined on human dental pulp stem cells (hDPSCs). To prove the successful encapsulation of DOX within the adhesives-but, more important, to support the hypothesis that the HNT+DOX adhesive would release DOX at subantimicrobial levels-we tested the antimicrobial activity of synthesized adhesives and the DOX-containing eluates against Streptococcus mutans through agar diffusion assays. Anti-MMP properties were assessed via β-casein cleavage assays. Increasing curing times (10, 20, 40 sec) led to increased DC values. There were no statistically significant differences (p > .05) in DC within each increasing curing time between the modified adhesives compared to SBMP. No statistically significant differences in microtensile bond strength were noted. None of the adhesives eluates were cytotoxic to the human dental pulp stem cells. A significant growth inhibition of S. mutans by direct contact illustrates successful encapsulation of DOX into the experimental adhesive. More important, DOX-containing eluates promoted inhibition of MMP-1 activity when compared to the control. Collectively, our findings provide a solid background for further testing of encapsulated MMP

  1. Minocycline and Doxycycline, but not Tetracycline, Mitigate Liver and Kidney Injury after Hemorrhagic Shock/Resuscitation*

    Science.gov (United States)

    Kholmukhamedov, Andaleb; Czerny, Christoph; Hu, Jiangting; Schwartz, Justin; Zhong, Zhi; Lemasters, John J.

    2014-01-01

    Background Despite recovery of hemodynamics by fluid resuscitation after hemorrhage, development of the systemic inflammatory response and multiple organ dysfunction syndromes can nonetheless lead to death. Minocycline and doxycycline are tetracycline derivatives that are protective in models of hypoxic, ischemic and oxidative stress. Our Aim was to determine whether minocycline and doxycycline protect liver and kidney and improve survival in a mouse model of hemorrhagic shock and resuscitation. Methods Mice were hemorrhaged to 30 mm Hg for 3 h and then resuscitated with shed blood followed by half the shed volume of lactated Ringer's solution containing tetracycline (10 mg/kg), minocycline (10 mg/kg), doxycycline (5 mg/kg) or vehicle. For pre-plus post-treatment, drugs were administered intraperitoneally prior to hemorrhage followed by second equal dose in Ringer's solution after blood resuscitation. Blood and tissue were harvested after 6 h. Results Serum alanine aminotransferase (ALT) increased to 1988 and 1878 U/L after post-treatment with vehicle and tetracycline, respectively, whereas minocycline and doxycycline post-treatment decreased ALT to 857 and 863 U/L. Pre-plus post-treatment with minocycline and doxycycline also decreased ALT to 849 and 834 U/L. After vehicle, blood creatinine increased to 279 μM, which minocycline and doxycycline post-treatment decreased to 118 and 112 μM. Minocycline and doxycycline pre- plus post-treatment decreased creatinine similarly. Minocycline and doxycycline also decreased necrosis and apoptosis in liver and apoptosis in both liver and kidney, the latter assessed by TUNEL and caspase-3 activation. Lastly after 4.5 h of hemorrhage followed by resuscitation, minocycline and doxycycline (but not tetracycline) post-treatment improved 1-week survival from 38%(vehicle) to 69% and 67%, respectively. Conclusion Minocycline and doxycycline were similarly protective when given before as after blood resuscitation and might therefore

  2. Airway-Specific Inducible Transgene Expression Using Aerosolized Doxycycline

    Science.gov (United States)

    Tata, Purushothama Rao; Pardo-Saganta, Ana; Prabhu, Mythili; Vinarsky, Vladimir; Law, Brandon M.; Fontaine, Benjamin A.; Tager, Andrew M.

    2013-01-01

    Tissue-specific transgene expression using tetracycline (tet)-regulated promoter/operator elements has been used to revolutionize our understanding of cellular and molecular processes. However, because most tet-regulated mouse strains use promoters of genes expressed in multiple tissues, to achieve exclusive expression in an organ of interest is often impossible. Indeed, in the extreme case, unwanted transgene expression in other organ systems causes lethality and precludes the study of the transgene in the actual organ of interest. Here, we describe a novel approach to activating tet-inducible transgene expression solely in the airway by administering aerosolized doxycycline. By optimizing the dose and duration of aerosolized doxycycline exposure in mice possessing a ubiquitously expressed Rosa26 promoter–driven reverse tet-controlled transcriptional activator (rtTA) element, we induce transgene expression exclusively in the airways. We detect no changes in the cellular composition or proliferative behavior of airway cells. We used this newly developed method to achieve airway basal stem cell–specific transgene expression using a cytokeratin 5 (also known as keratin 5)–driven rtTA driver line to induce Notch pathway activation. We observed a more robust mucous metaplasia phenotype than in mice receiving doxycycline systemically. In addition, unwanted phenotypes outside of the lung that were evident when doxycycline was received systemically were now absent. Thus, our approach allows for rapid and efficient airway-specific transgene expression. After the careful strain by strain titration of the dose and timing of doxycycline inhalation, a suite of preexisting transgenic mice can now be used to study airway biology specifically in cases where transient transgene expression is sufficient to induce a phenotype. PMID:23848320

  3. Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach.

    Directory of Open Access Journals (Sweden)

    Neha Nanda

    Full Text Available Doxycycline (DOX exhibits anti-inflammatory, anti-tumor, and pro-apoptotic activity and is being tested in clinical trials as a chemotherapeutic agent for several cancers, including colon cancer.In the current study, the chemotherapeutic activity of doxycycline was tested in a rat model of colon carcinogenesis, induced by colon specific cancer promoter, 1,2, dimethylhydrazine (DMH as well as study the effect of DOX-alone on a separate group of rats.Doxycycline administration in DMH-treated rats (DMH-DOX unexpectedly increased tumor multiplicity, stimulated progression of colonic tumor growth from adenomas to carcinomas and revealed metastasis in small intestine as determined by macroscopic and histopathological analysis. DOX-alone treatment showed markedly enhanced chronic inflammation and reactive hyperplasia, which was dependent upon the dose of doxycycline administered. Moreover, immunohistochemical analysis revealed evidence of inflammation and anti-apoptotic action of DOX by deregulation of various biomarkers.These results suggest that doxycycline caused chronic inflammation in colon, small intestine injury, enhanced the efficacy of DMH in tumor progression and provided a mechanistic link between doxycycline-induced chronic inflammation and tumorigenesis. Ongoing studies thus may need to focus on the molecular mechanisms of doxycycline action, which lead to its inflammatory and tumorigenic effects.

  4. Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach.

    Science.gov (United States)

    Nanda, Neha; Dhawan, Devinder K; Bhatia, Alka; Mahmood, Akhtar; Mahmood, Safrun

    2016-01-01

    Doxycycline (DOX) exhibits anti-inflammatory, anti-tumor, and pro-apoptotic activity and is being tested in clinical trials as a chemotherapeutic agent for several cancers, including colon cancer. In the current study, the chemotherapeutic activity of doxycycline was tested in a rat model of colon carcinogenesis, induced by colon specific cancer promoter, 1,2, dimethylhydrazine (DMH) as well as study the effect of DOX-alone on a separate group of rats. Doxycycline administration in DMH-treated rats (DMH-DOX) unexpectedly increased tumor multiplicity, stimulated progression of colonic tumor growth from adenomas to carcinomas and revealed metastasis in small intestine as determined by macroscopic and histopathological analysis. DOX-alone treatment showed markedly enhanced chronic inflammation and reactive hyperplasia, which was dependent upon the dose of doxycycline administered. Moreover, immunohistochemical analysis revealed evidence of inflammation and anti-apoptotic action of DOX by deregulation of various biomarkers. These results suggest that doxycycline caused chronic inflammation in colon, small intestine injury, enhanced the efficacy of DMH in tumor progression and provided a mechanistic link between doxycycline-induced chronic inflammation and tumorigenesis. Ongoing studies thus may need to focus on the molecular mechanisms of doxycycline action, which lead to its inflammatory and tumorigenic effects.

  5. The effect of subantimicrobial-dose–doxycycline periodontal therapy on serum biomarkers of systemic inflammation A randomized, double-masked, placebo-controlled clinical trial

    National Research Council Canada - National Science Library

    Jeffrey B. Payne; Lorne M. Golub; Julie A. Stoner; Hsi-ming Lee; Richard A. Reinhardt; Timo Sorsa; Marvin J. Slepian

    2011-01-01

    Periodontitis has been reported to be associated with coronary artery disease (CAD). Research is needed to determine if therapies that improve periodontal health also reduce systemic measures of inflammation associated with both diseases...

  6. Doxycycline in Eradication Therapy of Helicobacter pylori--a Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Niv, Yaron

    2016-01-01

    Since resistance of Helicobacter pylori is developing very fast all over the world, new treatment regimens for eradication are urgently needed. To compare eradication success rate of H. pylori treatment regimens with and without doxycycline. English medical literature searches were conducted for regimens including doxycycline for eradication of H. pylori. Searches were performed up to August 31, 2015, using MEDLINE, PubMed, EMBASE, Scopus and CENTRAL. Meta-analysis was performed by using comprehensive meta-analysis software. Pooled ORs and 95% CIs were calculated comparing treatment regimens for eradication of H. pylori infection with and without doxycycline. The OR for eradication success rate in a fixed model was in favor for treatment regimens with doxycycline: 1.292, 95% CI 1.048-1.594, p = 0.016. There was no significant heterogeneity in the included studies: Q = 15.130, d.f. (Q) = 8, I2 = 47.126, p > 0.10. When treatment regimens with doxycycline were compared only with treatment regimens with tetracycline, no significant difference was found in eradication success rate: OR 0.95, 95% CI 0.68-1.32, p = 0.77. But when treatment regimens with doxycycline were compared with treatment regimens without tetracycline, the OR in favor of doxycycline was even higher: OR 1.59, 95% CI 1.21-2.09, p doxycycline efficiency in the eradication of H. pylori. Thus, triple, quadruple or even high dose dual therapy with regimens containing doxycycline should be considered. © 2016 S. Karger AG, Basel.

  7. Azithromycin versus Doxycycline for Urogenital Chlamydia trachomatis Infection.

    Science.gov (United States)

    Geisler, William M; Uniyal, Apurva; Lee, Jeannette Y; Lensing, Shelly Y; Johnson, Shacondra; Perry, Raymond C W; Kadrnka, Carmel M; Kerndt, Peter R

    2015-12-24

    Urogenital Chlamydia trachomatis infection remains prevalent and causes substantial reproductive morbidity. Recent studies have raised concern about the efficacy of azithromycin for the treatment of chlamydia infection. We conducted a randomized trial comparing oral azithromycin with doxycycline for the treatment of urogenital chlamydia infection among adolescents in youth correctional facilities, to evaluate the noninferiority of azithromycin (1 g in one dose) to doxycycline (100 mg twice daily for 7 days). The treatment was directly observed. The primary end point was treatment failure at 28 days after treatment initiation, with treatment failure determined on the basis of nucleic acid amplification testing, sexual history, and outer membrane protein A (OmpA) genotyping of C. trachomatis strains. Among the 567 participants enrolled, 284 were randomly assigned to receive azithromycin, and 283 were randomly assigned to receive doxycycline. A total of 155 participants in each treatment group (65% male) made up the per-protocol population. There were no treatment failures in the doxycycline group. In the azithromycin group, treatment failure occurred in 5 participants (3.2%; 95% confidence interval, 0.4 to 7.4%). The observed difference in failure rates between the treatment groups was 3.2 percentage points, with an upper boundary of the 90% confidence interval of 5.9 percentage points, which exceeded the prespecified absolute 5-percentage-point cutoff for establishing the noninferiority of azithromycin. In the context of a closed population receiving directly observed treatment for urogenital chlamydia infection, the efficacy of azithromycin was 97%, and the efficacy of doxycycline was 100%. The noninferiority of azithromycin was not established in this setting. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00980148.).

  8. Doxycycline reverses epithelial-to-mesenchymal transition and suppresses the proliferation and metastasis of lung cancer cells.

    Science.gov (United States)

    Qin, Yuan; Zhang, Qiang; Lee, Shan; Zhong, Wei-Long; Liu, Yan-Rong; Liu, Hui-Juan; Zhao, Dong; Chen, Shuang; Xiao, Ting; Meng, Jing; Jing, Xue-Shuang; Wang, Jing; Sun, Bo; Dai, Ting-Ting; Yang, Cheng; Sun, Tao; Zhou, Hong-Gang

    2015-12-01

    The gelatinase inhibitor doxycycline is the prototypical antitumor antibiotic. We investigated the effects of doxycycline on the migration, invasion, and metastasis of human lung cancer cell lines and in a mouse model. We also measured the effect of doxycycline on the transcription of epithelial-mesenchymal transition (EMT) markers, and used immunohistochemistry to determine whether EMT reversal was associated with doxycycline inhibition. Doxycycline dose-dependently inhibited proliferation, migration, and invasion of NCI-H446 human small cell lung cancer cells. It also suppressed tumor growth from NCI-H446 and A549 lung cancer cell xenografts without altering body weight, inhibited Lewis lung carcinoma cell migration, and prolonged survival. The activities of the transcription factors Twist1/2, SNAI1/2, AP1, NF-κB, and Stat3 were suppressed by doxycycline, which reversed EMT and inhibited signal transduction, thereby suppressing tumor growth and metastasis. Our data demonstrate functional targeting of transcription factors by doxycycline to reverse EMT and suppress tumor proliferation and metastasis. Thus, doxycycline selectively targets malignant tumors and reduces its metastatic potential with less cytotoxicity in lung cancer patients.

  9. Pharmacokinetics of an oral extended-release formulation of doxycycline hyclate containing acrylic acid and polymethacrylate in dogs.

    Science.gov (United States)

    Ruiz, Sara Melisa Arciniegas; Olvera, Lilia Gutiérrez; Chacón, Sara del Carmen Caballero; Estrada, Dinorah Vargas

    2015-04-01

    To determine the pharmacokinetics of doxycycline hyclate administered orally in the form of experimental formulations with different proportions of acrylic acid-polymethacrylate-based matrices. 30 healthy adult dogs. In a crossover study, dogs were randomly assigned (in groups of 10) to receive a single oral dose (20 mg/kg) of doxycycline hyclate without excipients (control) or extended-release formulations (ERFs) containing doxycycline, acrylic acid polymer, and polymethacrylate in the following proportions: 1:0.5:0.0075 (ERF1) or 1:1:0.015 (ERF2). Serum concentrations of doxycycline were determined for pharmacokinetic analysis before and at several intervals after each treatment. Following oral administration to the study dogs, each ERF resulted in therapeutic serum doxycycline concentrations for 48 hours, whereas the control treatment resulted in therapeutic serum doxycycline concentrations for only 24 hours. All pharmacokinetic parameters for ERF1 and ERF2 were significantly different; however, findings for ERF1 did not differ significantly from those for the control treatment. Results indicated that both ERFs containing doxycycline, acrylic acid polymer, and polymethacrylate had an adequate pharmacokinetic-pharmacodynamic relationship for a time-dependent drug and a longer release time than doxycycline alone following oral administration in dogs. Given the minimum effective serum doxycycline concentration of 0.26 μg/mL, a dose interval of 48 hours can be achieved for each tested ERF. This minimum inhibitory concentration has the potential to be effective against several susceptible bacteria involved in important infections in dogs. Treatment of dogs with either ERF may have several benefits over treatment with doxycycline alone.

  10. Effect of doxycycline in patients of moderate to severe chronic obstructive pulmonary disease with stable symptoms

    Directory of Open Access Journals (Sweden)

    Prashant S Dalvi

    2011-01-01

    Full Text Available Background: The protease-antiprotease hypothesis proposes that inflammatory cells and oxidative stress in chronic obstructive pulmonary disease (COPD produce increased levels of proteolytic enzymes (neutrophil elastase, matrix metalloproteinases [MMP] which contribute to destruction of parenchyma resulting in progressive decline in forced expiratory volume in one second. Doxycycline, a tetracycline analogue, possesses anti-inflammatory properties and inhibits MMP enzymes. Objectives: To assess the effect of 4 weeks doxycycline in a dose of 100 mg once a day in patients of moderate to severe COPD with stable symptoms. Methods : In an interventional, randomized, observer-masked, parallel study design, the effect of doxycycline (100 mg once a day for 4 weeks was assessed in patients of COPD having stable symptoms after a run-in period of 4 weeks. The study participants in reference group did not receive doxycycline. The parameters were pulmonary functions, systemic inflammation marker C-reactive protein (CRP, and medical research council (MRC dyspnea scale. Use of systemic corticosteroids or antimicrobial agents was not allowed during the study period. Results: A total of 61 patients completed the study (31 patients in doxycycline group and 30 patients in reference group. At 4 weeks, the pulmonary functions significantly improved in doxycycline group and the mean reduction in baseline serum CRP was significantly greater in doxycycline group as compared with reference group. There was no significant improvement in MRC dyspnea scale in both groups at 4 weeks. Conclusion: The anti-inflammatory and MMP-inhibiting property of doxycycline might have contributed to the improvement of parameters in this study.

  11. Doxycycline

    Science.gov (United States)

    ... may have been exposed to anthrax in the air, and to treat plague and tuleramia (serious infections ... decrease the effectiveness of hormonal contraceptives (birth control pills, patches, rings, or injections). Talk to your doctor ...

  12. Doxycycline Attenuated Pulmonary Fibrosis Induced by Bleomycin in Mice

    OpenAIRE

    Fujita, Masaki; Ye, Qing; Ouchi, Hiroshi; Harada, Eiji; Inoshima, Ichiro; Kuwano, Kazuyoshi; Nakanishi, Yoichi

    2006-01-01

    The administration of doxycycline prior to bleomycin in mice attenuated pulmonary fibrosis. Bronchoalveolar neutrophil influx and gelatinase activity, but not caseinolytic activity, were attenuated by doxycycline. Established fibrosis was not affected by doxycycline. Thus, doxycycline might be useful for slowing down pulmonary fibrosis by biological activity other than antibacterial activity.

  13. Evaluation of canine-specific minocycline and doxycycline susceptibility breakpoints for meticillin-resistant Staphylococcus pseudintermedius isolates from dogs.

    Science.gov (United States)

    Hnot, Melanie L; Cole, Lynette K; Lorch, Gwendolen; Papich, Mark G; Rajala-Schultz, Paivi J; Daniels, Joshua B

    2015-10-01

    Using the US Clinical and Laboratory Standards Institute (CLSI) human tetracycline breakpoints to predict minocycline and doxycycline susceptibility of Staphylococcus pseudintermedius (SP) isolates from dogs is not appropriate because they are too high to meet pharmacokinetic/pharmacodynamic data using a standard dose. New breakpoints have been approved for doxycycline and proposed for minocycline. Revised breakpoints are four dilutions lower than tetracycline breakpoints, providing a more conservative standard for classification of isolates. The objectives of this study were to measure minimum inhibitory concentrations (MICs) of minocycline and doxycycline of 100 canine meticillin-resistant SP clinical isolates, compare their susceptibilities to minocycline and doxycycline based on current and revised standards, and document their tetracycline resistance genes. E-test strips were used to determine MICs. PCR was used to identify tet genes. Using the human tetracycline breakpoint of MIC ≤ 4 μg/mL, 76 isolates were susceptible to minocycline and 36 isolates were susceptible to doxycycline. In contrast, using the proposed minocycline breakpoint (MIC ≤ 0.25 μg/mL) and approved doxycycline breakpoint (MIC ≤ 0.125 μg/mL), 31 isolates were susceptible to both minocycline and doxycycline. Thirty-one isolates carried no tet genes, two had tet(K) and 67 had tet(M). Use of the human tetracycline breakpoints misclassified 45 and five of the isolates as susceptible to minocycline and doxycycline, respectively. PCR analysis revealed that 43 and five of the isolates classified as susceptible to minocycline and doxycycline, respectively, possessed the tetracycline resistance gene, tet(M), known to confer resistance to both drugs. These results underscore the importance of utilizing the proposed minocycline and approved doxycycline canine breakpoints in place of human tetracycline breakpoints. © 2015 ESVD and ACVD.

  14. Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration.

    Science.gov (United States)

    Freeman, Kate S; Thomasy, Sara M; Stanley, Scott D; Van Bonn, William; Gulland, Frances; Friedlaender, Ari S; Maggs, David J

    2013-10-15

    To assess tear and plasma concentrations of doxycycline following oral administration to northern elephant seals (Mirounga angustirostris). Pharmacokinetic study. 18 juvenile northern elephant seals without signs of ocular disease. Study seals were receiving no medications other than a multivitamin and were free from signs of ocular disease as assessed by an ophthalmic examination. Doxycycline (10 or 20 mg/kg [4.5 or 9.1 mg/lb]) was administered orally every 24 hours for 4 days. Tear and plasma samples were collected at fixed time points, and doxycycline concentration was assessed by means of liquid chromatography-tandem mass spectrometry. Concentration-time data were calculated via noncompartmental analysis. Following administration of doxycycline (10 mg/kg/d, PO), maximum plasma doxycycline concentration was 2.2 μg/mL at 6.1 hours on day 1 and was 1.5 μg/mL at 4.0 hours on day 4. Administration of doxycycline (20 mg/kg/d, PO) produced a maximum plasma doxycycline concentration of 2.4 μg/mL at 2.3 hours on day 1 and 1.9 μg/mL at 5.8 hours on day 4. Doxycycline elimination half-life on day 4 in animals receiving doxycycline at a dosage of 10 or 20 mg/kg/d was 6.7 or 5.6 hours, respectively. Mean plasma-to-tear doxycycline concentration ratios over all days were not significantly different between the low-dose (9.85) and high-dose (9.83) groups. For both groups, doxycycline was detectable in tears for at least 6 days following cessation of dosing. Oral administration of doxycycline at the doses tested in the present study resulted in concentrations in the plasma and tears of northern elephant seals likely to be clinically effective for treatment of selected cases of systemic infectious disease, bacterial ulcerative keratitis, and ocular surface inflammation. This route of administration should be considered for treatment of corneal disease in northern elephant seals and possibly other related pinniped species.

  15. Phototoxicity of Doxycycline: A Systematic Review on Clinical Manifestations, Frequency, Cofactors, and Prevention.

    Science.gov (United States)

    Goetze, Steven; Hiernickel, Christian; Elsner, Peter

    2017-01-01

    One of the most important dermatologic side effects of doxycycline is photosensitivity. As doxycycline is important for malaria prophylaxis and malaria is mainly spread in countries with high sun radiation, special attention should be paid to this adverse effect. While there are many publications on the phototoxicity of tetracyclines in general, only a few exist focusing on doxycycline. The objective of this systematic review was to summarize all available reports on clinical manifestations, influencing factors like UV dose or dose of medication, and the possibilities of prevention by sun protection. This review is based on a systematic search in PubMed for articles in English and German and a manual search between 1990 and 2015. The number of publications is low. Clinical symptoms vary from light sunburn-like sensation (burning, erythema) to large-area photodermatitis. Also, onycholysis is possible. The triggering UV spectrum seems to consist mainly of UVA1 (340-400 nm), so UV-protective products should be used that cover this range. Travelers to tropical countries taking doxycycline for malaria prophylaxis need thorough medical counseling to avoid possibly severe phototoxic reactions. Evidence base must be improved for giving advice on appropriate prevention measures to travelers taking doxycycline and having a risk of significant sun exposure. © 2017 S. Karger AG, Basel.

  16. Doxycycline Stabilizes Vulnerable Plaque via Inhibiting Matrix Metalloproteinases and Attenuating Inflammation in Rabbits

    Science.gov (United States)

    Dong, Mei; Zhong, Lin; Chen, Wen Qiang; Ji, Xiao Ping; Zhang, Mei; Zhao, Yu Xia; Li, Li; Yao, Gui Hua; Zhang, Peng Fei; Zhang, Cheng; Zhang, Lei; Zhang, Yun

    2012-01-01

    Enhanced matrix metalloproteinases (MMPs) activity is implicated in the process of atherosclerotic plaque instability. We hypothesized that doxycycline, a broad MMPs inhibitor, was as effective as simvastatin in reducing the incidence of plaque disruption. Thirty rabbits underwent aortic balloon injury and were fed a high-fat diet for 20 weeks. At the end of week 8, the rabbits were divided into three groups for 12-week treatment: a doxycycline-treated group that received oral doxycycline at a dose of 10 mg/kg/d, a simvastatin-treated group that received oral simvastatin at a dose of 5 mg/kg/d, and a control group that received no treatment. At the end of week 20, pharmacological triggering was performed to induce plaque rupture. Biochemical, ultrasonographic, pathologic, immunohistochemical and mRNA expression studies were performed. The results showed that oral administration of doxycycline resulted in a significant increase in the thickness of the fibrous cap of the aortic plaque whereas there was a substantial reduction of MMPs expression, local and systemic inflammation, and aortic plaque vulnerability. The incidence of plaque rupture with either treatment (0% for both) was significantly lower than that for controls (56.0%, Pdoxycycline-treated group and simvastatin-treated group in any serological, ultrasonographic, pathologic, immunohistochemical and mRNA expression measurement except for the serum lipid levels that were higher with doxycycline than with simvastatin treatment. In conclusion, doxycycline at a common antimicrobial dose stabilizes atherosclerotic lesions via inhibiting matrix metalloproteinases and attenuating inflammation in a rabbit model of vulnerable plaque. These effects were similar to a large dose of simvastatin and independent of serum lipid levels. PMID:22737253

  17. Doxycycline inhibits proliferation and induces apoptosis of both human papillomavirus positive and negative cervical cancer cell lines.

    Science.gov (United States)

    Zhao, Yan; Wang, Xinyu; Li, Lei; Li, Changzhong

    2016-05-01

    The clinical management of cervical cancer remains a challenge and the development of new treatment strategies merits attention. However, the discovery and development of novel compounds can be a long and labourious process. Drug repositioning may circumvent this process and facilitate the rapid translation of hypothesis-driven science into the clinics. In this work, we show that a FDA-approved antibiotic, doxycycline, effectively targets human papillomavirus (HPV) positive and negative cervical cancer cells in vitro and in vivo. Doxycycline significantly inhibits proliferation of a panel of cervical cancer cell lines. It also induces apoptosis of cervical cancer cells in a time- and dose-dependent manner. In addition, the apoptosis induced by doxycycline is through caspase-dependent pathway. Mechanism studies demonstrate that doxycycline affects oxygen consumption rate, glycolysis, and reduces ATP levels in cervical cancer cells. In HeLa xenograft mouse model, doxycycline significantly inhibits growth of tumour. Our in vitro and in vivo data clearly demonstrate the inhibitory effects of doxycycline on the growth and survival of cervical cancer cells. Our work provides the evidence that doxycycline can be repurposed for the treatment of cervical cancer and targeting energy metabolism may represent a potential therapeutic strategy for cervical cancer.

  18. Probable doxycycline-induced acute pancreatitis.

    Science.gov (United States)

    Moy, Brian T; Kapila, Nikhil

    2016-03-01

    A probable case of doxycycline-induced pancreatitis is reported. A 51-year-old man was admitted to the emergency department with a one-week history of extreme fatigue, malaise, and confusion. Three days earlier he had been started on empirical doxycycline therapy for presumed Lyme disease; he was taking no other medications at the time of admission. A physical examination was remarkable for abdominal tenderness. Relevant laboratory data included a lipase concentration of 5410 units/L (normal range, 13-60 units/L), an amylase concentration of 1304 (normal range, 28-100 units/L), and a glycosylated hemoglobin concentration of 15.2% (normal, doxycycline was discontinued. With vasopressor support, aggressive fluid resuscitation, hemodialysis, and an insulin infusion, the patient's clinical course rapidly improved over five days. Scoring of the case via the method of Naranjo et al. yielded a score of 6, indicating a probable adverse reaction to doxycycline. A man developed AP three days after starting therapy with oral doxycycline, and the association between drug and reaction was determined to be probable. His case appears to be the third of doxycycline-associated AP, although tigecycline, tetracycline, and minocycline have also been implicated as causes of AP. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  19. Doxycycline inhibits TGF-β1-induced extracellular matrix production in nasal polyp-derived fibroblasts.

    Science.gov (United States)

    Shin, Jae-Min; Park, Joo-Hoo; Park, Il-Ho; Lee, Heung-Man

    2016-03-01

    Doxycycline has been shown to have antibacterial and anti-inflammatory effects and suppresses collagen biosynthesis. The purpose of this study was to evaluate the effects of doxycycline on transforming growth factor (TGF)-β1-induced myofibroblast differentiation and extracellular matrix production in nasal polyp-derived fibroblasts (NPDFs). We also determined the molecular mechanisms of action for doxycycline. NPDFs were isolated from nasal polyps from 8 patients. Doxycycline was used to pretreat TGF-β1-induced NPDFs. Cytotoxicity was evaluated using a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay. Expression levels of α-smooth muscle actin (SMA) and fibronectin were measured using Western blot, reverse-transcription polymerase chain reaction, and immunofluorescence staining. Total collagen production was analyzed with the Sircol collagen assay, while mitogen-activated protein kinase (MAPK) and NF-κB activation were determined using Western blot analysis. Luciferase assay was used to evaluate the transcriptional activity of NF-κB. Although doxycycline (0 to 40 μg/mL) had no significant cytotoxic effects in TGF-β1-induced NPDFs, it significantly reduced the expression levels of α-SMA, fibronectin, and collagen in TGF-β1-induced NPDFs in a dose-dependent manner. Doxycycline also inhibited the TGF-β1-induced activation of p38, c-Jun NH2 -terminal kinase (JNK), and NF-κB, and its inhibitory effects were similar to those of the specific inhibitors for each. Doxycycline has an inhibitory effect on TGF-β1-induced myofibroblast differentiation and extracellular matrix production via the p38 and JNK/NF-κB signal pathways in NPDFs. © 2015 ARS-AAOA, LLC.

  20. Molecular effects of doxycycline treatment on pterygium as revealed by massive transcriptome sequencing.

    Directory of Open Access Journals (Sweden)

    Ignacio M Larráyoz

    Full Text Available Pterygium is a lesion of the eye surface which involves cell proliferation, migration, angiogenesis, fibrosis, and extracellular matrix remodelling. Surgery is the only approved method to treat this disorder, but high recurrence rates are common. Recently, it has been shown in a mouse model that treatment with doxycycline resulted in reduction of the pterygium lesions. Here we study the mechanism(s of action by which doxycycline achieves these results, using massive sequencing techniques. Surgically removed pterygia from 10 consecutive patients were set in short term culture and exposed to 0 (control, 50, 200, and 500 µg/ml doxycycline for 24 h, their mRNA was purified, reverse transcribed and sequenced through Illumina's massive sequencing protocols. Acquired data were subjected to quantile normalization and analyzed using cytoscape plugin software to explore the pathways involved. False discovery rate (FDR methods were used to identify 332 genes which modified their expression in a dose-dependent manner upon exposure to doxycycline. The more represented cellular pathways included all mitochondrial genes, the endoplasmic reticulum stress response, integrins and extracellular matrix components, and growth factors. A high correlation was obtained when comparing ultrasequencing data with qRT-PCR and ELISA results. Doxycycline significantly modified the expression of important cellular pathways in pterygium cells, in a way which is consistent with the observed efficacy of this antibiotic to reduce pterygium lesions in a mouse model. Clinical trials are under way to demonstrate whether there is a benefit for human patients.

  1. Susceptibility of Porphyromonas gingivalis in biofilms to amoxicillin, doxycycline and metronidazole

    DEFF Research Database (Denmark)

    Larsen, T.

    2002-01-01

    Biofilm, Porphyromonas gingivalis, susceptibility testing, amoxicillin, doxycycline, metronidazole......Biofilm, Porphyromonas gingivalis, susceptibility testing, amoxicillin, doxycycline, metronidazole...

  2. Doxycycline Degradation by the Oxidative Fenton Process

    Directory of Open Access Journals (Sweden)

    Alexandre A. Borghi

    2015-01-01

    Full Text Available Doxycycline is a broad-spectrum tetracycline occurring in domestic, industrial, and rural effluents, whose main drawback is the increasing emergence of resistant bacteria. This antibiotic could be degraded by the so-called Fenton process, consisting in the oxidation of organic pollutants by oxygen peroxide (H2O2 in the presence of Fe2+. Experiments were performed according to an experimental Rotational Central Composite Design to investigate the influence of temperature (0–40.0°C, H2O2 concentration (100–900 mg/L, and Fe2+ concentration (5–120 mg/L on residual doxycycline and total organic carbon concentrations. Whereas the final residual doxycycline concentration ranged from 0 to 55.8 mg/L, the oxidation process proved unable to reduce the total organic carbon by more than 30%. The best operating conditions were concentrations of H2O2 and Fe2+ of 611 and 25 mg/L, respectively, and temperature of 35.0°C, but the analysis of variance revealed that only the first variable exerted a statistically significant effect on the residual doxycycline concentration. These results suggest possible application of this process in the treatment of doxycycline-containing effluents and may be used as starting basis to treat tetracycline-contaminated effluents.

  3. Doxycycline sclerotherapy in children with head and neck lymphatic malformations.

    Science.gov (United States)

    Cheng, Jeffrey

    2015-12-01

    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. PubMed, EMBASE, and Ovid. 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. 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). 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Pharmacodynamics of Doxycycline in a Murine Malaria Model▿

    OpenAIRE

    Batty, Kevin T.; Law, Angela S. F.; Stirling, Verity; Moore, Brioni R

    2007-01-01

    Doxycycline is reported to impair second-generation parasite schizogony. The effects of doxycycline alone and combined with dihydroartemisinin were investigated in a murine malaria model. Doxycycline lowered the rate of parasite growth within 2 days, with maximum effect in 6 days. Addition of dihydroartemisinin led to an additive antimalarial effect.

  5. Doxycycline in the Treatment :uncomplicated Gonorrohea

    Directory of Open Access Journals (Sweden)

    S L Wadhwa

    1979-01-01

    Full Text Available Gonorrhoea constitutes nine per cent of the sexually transmitted diseases seen at the department of Dermatology and Venereology, Nair Hospital, Bombay. Fifty cases of uncomplicated males were treated with doxycycline 200mgs iv on the first day and 100 mgs, iv for 2 more - a total of 400 mgs doxycycline. Smears for gonococci and blood V D R L were treatment. The cases were reviewed every week for a period 3 weeks. Three cases showed a positive serology and 44 cases responded well to therapy giving a success rate of 88%. Side effects were minimal.

  6. Effects of oral administration of metronidazole and doxycycline on olfactory capabilities of explosives detection dogs.

    Science.gov (United States)

    Jenkins, Eileen K; Lee-Fowler, Tekla M; Angle, T Craig; Behrend, Ellen N; Moore, George E

    2016-08-01

    OBJECTIVE To determine effects of oral administration of metronidazole or doxycycline on olfactory function in explosives detection (ED) dogs. ANIMALS 18 ED dogs. PROCEDURES Metronidazole was administered (25 mg/kg, PO, q 12 h for 10 days); the day prior to drug administration was designated day 0. Odor detection threshold was measured with a standard scent wheel and 3 explosives (ammonium nitrate, trinitrotoluene, and smokeless powder; weight, 1 to 500 mg) on days 0, 5, and 10. Lowest repeatable weight detected was recorded as the detection threshold. There was a 10-day washout period, and doxycycline was administered (5 mg/kg, PO, q 12 h for 10 days) and the testing protocol repeated. Degradation changes in the detection threshold for dogs were assessed. RESULTS Metronidazole administration resulted in degradation of the detection threshold for 2 of 3 explosives (ammonium nitrate and trinitrotoluene). Nine of 18 dogs had a degradation of performance in response to 1 or more explosives (5 dogs had degradation on day 5 or 10 and 4 dogs had degradation on both days 5 and 10). There was no significant degradation during doxycycline administration. CONCLUSIONS AND CLINICAL RELEVANCE Degradation in the ability to detect odors of explosives during metronidazole administration at 25 mg/kg, PO, every 12 hours, indicated a potential risk for use of this drug in ED dogs. Additional studies will be needed to determine whether lower doses would have the same effect. Doxycycline administered at the tested dose appeared to be safe for use in ED dogs.

  7. Pharmacodynamics of Doxycycline and Tetracycline against Staphylococcus pseudintermedius: Proposal of Canine-Specific Breakpoints for Doxycycline

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    Papich, Mark G.; Turnidge, John; Guardabassi, Luca

    2013-01-01

    Doxycycline is a tetracycline that has been licensed for veterinary use in some countries, but no clinical breakpoints are available for veterinary pathogens. The objectives of this study were (i) to establish breakpoints for doxycycline and (ii) to evaluate the use of tetracycline as a surrogate to predict the doxycycline susceptibility of Staphylococcus pseudintermedius isolates. MICs and inhibition zone diameters were determined for 168 canine S. pseudintermedius isolates according to Clinical and Laboratory Standards Institute (CLSI) standards. Tetracycline resistance genes were detected by PCR, and time-kill curves were determined for representative strains. In vitro pharmacodynamic and target animal pharmacokinetic data were analyzed by Monte Carlo simulation (MCS) for the development of MIC interpretive criteria. Optimal zone diameter breakpoints were defined using the standard error rate-bounded method. The two drugs displayed bacteriostatic activity and bimodal MIC distributions. Doxycycline was more active than tetracycline in non-wild-type strains. MCS and target attainment analysis indicated a certainty of ≥90% for attaining an area under the curve (AUC)/MIC ratio of >25 with a standard dosage of doxycycline (5 mg/kg of body weight every 12 h) for strains with MICs of ≤0.125 μg/ml. Tetracycline predicted doxycycline susceptibility, but current tetracycline breakpoints were inappropriate for the interpretation of doxycycline susceptibility results. Accordingly, canine-specific doxycycline MIC breakpoints (susceptible, ≤0.125 μg/ml; intermediate, 0.25 μg/ml; resistant, ≥0.5 μg/ml) and zone diameter breakpoints (susceptible, ≥25 mm; intermediate, 21 to 24 mm; resistant, ≤20 mm) and surrogate tetracycline MIC breakpoints (susceptible, ≤0.25 μg/ml; intermediate, 0.5 μg/ml; resistant, ≥1 μg/ml) and zone diameter breakpoints (susceptible, ≥23 mm; intermediate, 18 to 22 mm; resistant, ≤17 mm) were proposed based on the data generated

  8. Evaluation of the Doxycycline Release from AH26 Sealer-Doxycycline Combination: An ex vivo Study.

    Science.gov (United States)

    Ashofteh Yazdi, Kazem; Shokouhinejad, Noushin; Moazeni, Esmaeil; Mirzayi Rad, Sina

    2011-01-01

    The purpose of this ex vivo study was to determine the releasing characteristics and doxycycline dentinal diffusion of AH26 sealer-doxycycline combination from apical 3mm of tooth root and apical foramen. One-hundred and two recently extracted single-rooted human teeth were decoronated and prepared with #3 and #4 Gates-Glidden drills and rotary Mtwo files. Smear layer was removed; all surfaces except for apical 3mm of each root were sealed with two coats of nail polish. To quantify the release and diffusion of the doxycycline at different time intervals (30 min, 48 and 72 h) after root canal obturation, the samples were randomly divided into three groups (n=30; 0.5 h, 48 h, 72 h). To evaluate the release of doxycycline from AH26 sealer-doxycycline combination at six concentrations of antibiotic including 0.5%, 1%, 2%, 5%, 10% and 20%; each experimental group was divided into six equal subgroups (n=5). Root canals were filled with gutta-percha and AH26-doxycycline combinations and then were placed in vials containing 1.25mL of phosphate buffer saline solution (PBS). After 30 min, 48 and 72 h, the amount of doxycycline released from specimens into PBS were determined by measuring the absorbance values using UV spectrophotometry at λ(max)=350 nm. Data were analyzed using two-way ANOVA. The findings of this study revealed that AH26 sealer-doxycycline combination released variable measures of antibiotic at each time interval and in the various concentrations. At 30 min, no statistically significant differences were obtained between the results of subgroups, but at 48 and 72 h these differences were significant (P<0.001). The results also showed that differences between 0.5 h, 48 h and 72 h were significant within subgroups (P<0.01). Under the conditions of this ex vivo study, doxycycline can be released from AH26 sealer-antibiotic combination through 3mm of apical root and apical foramen at 30 min, 48 and 72 h after mixing the sealer with doxycycline at concentrations

  9. The efficacy of a generic doxycycline tablet in the treatment of canine monocytic ehrlichiosis

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    Josephus J. Fourie

    2015-03-01

    Full Text Available The objective of the present study was to evaluate the therapeutic efficacy of a generic doxycycline tablet (DoxyVet® against Ehrlichia canis infection in dogs. Canine monocytic ehrlichiosis is caused by the bacterium E. canis and transmitted by the brown kennel tick (Rhipicephalus sanguineus. Six disease-free and tick-free dogs were infested with E. canis infected ticks. Once diagnosed (with polymerase chain reaction [PCR] analysis and platelet counts as positive for infection, doxycycline tablets were administered orally once a day for 20 consecutive days, at a target dose level of 10 mg/kg. The actual dose administered was calculated as ranging between 10 mg/kg and 11.7 mg/kg. The PCR analysis, 28 days after the first administration of the tablets, failed to detect E. canis in any of the dogs. On Day 56 of the study, four of the dogs were diagnosed with E. canis for the second time and a fifth dog was diagnosed on Day 70. The platelet counts of the sixth dog remained within normal levels and it was discharged from the study on Day 84. Doxycycline tablets were then administered to the remaining five infected dogs for 28 consecutive days. Four of these dogs had no positive PCR results during the following 3 months. The fifth dog was diagnosed with E. canis for the third time 58 days after the last tablets of the second treatment had been administered, after which it was rescue treated (doxycycline for a further 28 days. The results indicate that doxycycline administered in tablet form (DoxyVet® at 10 mg/kg – 11.7 mg/kg body mass once daily for 28 consecutive days clears most dogs of infection. The importance of a concomitant tick-control programme is therefore stressed.

  10. Local delivery system of doxycycline hyclate based on ε-caprolactone copolymers for periodontitis treatment.

    Science.gov (United States)

    Kopytynska-Kasperczyk, Anna; Dobrzynski, Piotr; Pastusiak, Małgorzata; Jarzabek, Bozena; Prochwicz, Wojciech

    2015-08-01

    The aim of the study was to evaluate kinetics of doxycycline hyclate release from polymeric bioresorbable implants and to examine suitability of this system for local treatment of periodontitis. Selected trimethylene carbonate/ϵ-caprolactone (TMC/CL) and glycolide/caprolactone (GL/CL) copolymers were synthesized and used as carriers in the form of small elastic rings with 5 wt% and 10 wt% doxycycline hyclate content, or in the form of flakes obtained through electro-spinning technique. The release of the drug under in vitro conditions has been tested. The study has shown that equimolar TMC/CL copolymer loaded with 10 wt% of doxycycline hyclate appears to be the most suitable copolymer for assumed system. The drug release proceeds mainly by diffusion of medium into the polymeric matrix and then the drug is washed out. Daily validation of doxycycline doses released by the system should ensure accurate course of the therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Doxycycline Inhibits Polarization of Macrophages to the Proangiogenic M2-type and Subsequent Neovascularization*

    Science.gov (United States)

    He, Lizhi; Marneros, Alexander G.

    2014-01-01

    Macrophages occur along a continuum of functional states between M1-type polarized macrophages with antiangiogenic and antitumor activity and M2-type polarized macrophages, which have been implicated to promote angiogenesis and tumor growth. Proangiogenic M2-type macrophages promote various pathologic conditions, including choroidal neovascularization in models of neovascular age-related macular degeneration, or certain cancers, such as glioblastoma multiforme. Thus, a potential novel therapeutic approach to target pathological angiogenesis in these conditions would be to inhibit the polarization of macrophages toward the proangiogenic M2-type. However, no pharmacological inhibitors of M2-type macrophage polarization have been identified yet. Here we performed an unbiased pharmacological and small chemical screen to identify drugs that inhibit proangiogenic M2-type macrophage polarization and block pathologic macrophage-driven neovascularization. We identified the well tolerated and commonly used antibiotic doxycycline as a potent inhibitor of M2-type polarization of macrophages. Doxycycline inhibited, in a dose-dependent manner, M2-type polarization of human and bone marrow-derived mouse macrophages without affecting cell viability. Furthermore, doxycycline inhibited M2-type macrophage polarization and subsequent neovascularization in vivo in a laser injury model of choroidal neovascularization. Thus, doxycycline could be used to enhance current antiangiogenic treatment approaches in various conditions that are promoted by proangiogenic M2-type macrophages, including neovascular age-related macular degeneration and certain cancers. PMID:24505138

  12. Doxycycline and Tigecycline: Two Friendly Drugs with a Low Association with Clostridium Difficile Infection

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    Yuan-Pin Hung

    2015-06-01

    Full Text Available Clostridium difficile infection (CDI is known to be associated with prior exposure to many classes of antibiotics. Standard therapy for CDI (i.e., metronidazole and vancomycin is associated with high recurrence rates. Although tetracycline derivatives such as tetracycline, doxycycline or tigecycline are not the standard therapeutic choices for CDI, they may serve as an alternative or a component of combination therapy. Previous tetracycline or doxycycline usage had been shown to have less association with CDI development. Tigecycline, a broad-spectrum glycylcycline with potency against many gram-positive or gram-negative pathogens, had been successfully used to treat severe or refractory CDI. The in vitro susceptibility of C. difficile clinical isolates to tigecycline in many studies showed low minimal inhibitory concentrations. Tigecycline can suppress in vitro toxin production in both historical and hypervirulent C. difficile strains and reduce spore production in a dose-dependent manner. Tetracycline compounds such as doxycycline, minocycline, and tigecycline possess anti-inflammatory properties that are independent of their antibiotic activity and may contribute to their therapeutic effect for CDI. Although clinical data are limited, doxycycline is less likely to induce CDI, and tigecycline can be considered one of the therapeutic choices for severe or refractory CDI.

  13. Doxycycline directly targets PAR1 to suppress tumor progression.

    Science.gov (United States)

    Zhong, Weilong; Chen, Shuang; Zhang, Qiang; Xiao, Ting; Qin, Yuan; Gu, Ju; Sun, Bo; Liu, Yanrong; Jing, Xiangyan; Hu, Xuejiao; Zhang, Peng; Zhou, Honggang; Sun, Tao; Yang, Cheng

    2017-03-07

    Doxycycline have been reported to exert anti-cancer activity and have been assessed as anti-cancer agents in clinical trials. However, the direct targets of doxycycline in cancer cells remain unclear. In this study, we used a chemical proteomics approach to identify the Protease-activated receptor 1 (PAR1) as a specific target of inhibition of doxycycline. Binding assays and single-molecule imaging assays were performed to confirm the inhibition of doxycycline to PAR1. The effect of doxycycline on multi-omics and cell functions were assessed based on a PAR1/thrombin model. Molecular docking and molecular dynamic simulations revealed that doxycycline interacts with key amino acids in PAR1. Mutation of PAR1 further confirmed the computation-based results. Moreover, doxycycline provides highly selective inhibition of PAR1 signaling in tumors in vitro and in vivo. Using pathological clinical samples co-stained for doxycycline and PAR1, it was found that doxycycline fluorescence intensity and PAR1 expression shown a clear positive correlation. Thus, doxycycline may be a useful targeted anti-cancer drug that should be further investigated in clinical trials.

  14. Comparative Efficacy of Penicillin and Doxycycline in Gonococcal Urethritis

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    Vinod K Sharma

    1987-01-01

    Full Text Available Ninety two episodes of gonococcal urethritis treated with one of the following regimens viz: (A 3 m. u. of fortified procaine penicillin made by adding 1 m.u. of crystalline penicillin to 2 m.u. of fortified procaine penicillin intramuscularly with one gram of probenecid orally, (B 3 m.u. of above fortified procaine penicillin intramuscularly alone, and (C 400 mg single oral dose of doxycycline produced success rates of 95,76.2 and 66.7% respectively. Post gonococcal urethritis was detected in 37% patients. Thirty four (45.94% of the 74 isolates of N. gonorrhoeae were relatively resistant (MIC 0. 12 units ml to penicillin. None of the 74 Neisseria gonorrhoeac strains was beta lactamase producing.

  15. In-vitro red blood cell partitioning of doxycycline

    OpenAIRE

    P.V. Deshmukh; Badgujar, P.C.; Gatne, M. M.

    2009-01-01

    Objective: In-vitro red blood cell (RBC) partitioning of doxycycline was studied to determine whether doxycycline penetrates RBC and its concentration was assayed keeping in view its high lipophilicity. Materials and Methods: Standardization of doxycycline was performed in whole blood and plasma of cattle by microbiological assay using Bacillus subtillis ATCC 6633 as indicator organizm. Actual concentration of the drug was obtained by comparing zone inhibition with standard graph and the exte...

  16. Doxycycline-induced drug fever: a case report.

    Science.gov (United States)

    Yuan, Hai-Ling; Lu, Ning-Wei; Xie, Hua; Zheng, Yuan-Yuan; Wang, Qiu-Hong

    2016-01-01

    Drug fever is a febrile reaction induced by a drug without additional clinical symptoms. This adverse reaction is not rare but under diagnosed and under reported. Doxycycline is a tetracycline compound with broad-spectrum antibiotic activity. Drug fever induced by doxycycline is rarely reported. In this study, we describe a patient in whom doxycycline induced drug fever after 17 days of therapy for brucellosis.

  17. Safety of doxycycline and minocycline: a systematic review.

    Science.gov (United States)

    Smith, Kelly; Leyden, James J

    2005-09-01

    The goal of this review was to summarize the available literature covering the safety profiles of oral doxycycline and minocycline. Scientific literature published between 1966 and August 2003 was searched using the MEDLINE, EMBASE, and Biosis databases (search terms: minocycline or doxycycline, each paired with adverse reaction, adverse event, and side effect, and doxycycline or minocycline with the limits English language, human, and clinical trials). Safety information was collected from case reports and clinical trials. Adverse event (AE) rates in the United States were calculated by comparing data from the MedWatch AE reporting program used by the US Food and Drug Administration (FDA) with the number of new prescriptions dispensed for each drug from January 1998 to August 2003. Between 1966 and 2003, a total of 130 and 333 AEs were published in case reports of doxycycline and minocycline, respectively. In 24 doxycycline clinical trials (n = 3833) and 11 minocycline trials (n = 788), the ranges in incidence of AEs were 0% to 61% and 11.7% to 83.3%, respectively. Gastrointestinal AEs were most common with doxycycline; central nervous system and gastrointestinal AEs were most common with minocycline. From January 1998 to August 2003, the FDA MedWatch data contained 628 events for doxycycline and 1099 events for minocycline reported in the United States. Approximately 47,630,000 doxycycline and 15,234,000 minocycline new prescriptions were dispensed in the United States during that period, yielding event rates of 13 per million for doxycycline and 72 per million for minocycline, based on FDA data. Between 1998 and 2003, doxycycline was prescribed 3 times as often as minocycline. The incidence of AEs with either drug is very low, but doxycycline had fewer reported AEs. Although more head-to-head clinical trials are needed for a direct comparison of AE frequency, these preliminary data from separate reports suggest the possibility that AEs may be less likely with

  18. Cutaneous side effects of doxycycline: a pediatric case series.

    Science.gov (United States)

    Bayhan, Gulsum Iclal; Akbayram, Sinan; Ozaydin Yavuz, Goknur; Oner, Ahmet Fayik

    2017-06-01

    Brucellosis is highly endemic in Turkey and doxycycline is commonly used for its treatment. The present study aimed at documenting the cutaneous side effects of doxycycline in pediatric brucellosis patients in Turkey. Pediatric patients with brucellosis that were treated between February 2014 and January 2016 were analyzed retrospectively, and those that developed doxycycline-related cutaneous side effects were identified. Demographic data, epidemiological history, physical examination findings, laboratory test results, anti-brucellosis treatment regimen, duration of follow up and outcome were recorded. Among the 189 brucellosis patients, 141 treated with doxycycline plus rifampicin. Seven patients (5%) (two female and five male) developed doxycycline-related cutaneous side effects. Mean duration of treatment before the onset of cutaneous side effects was 9.5 weeks. Doxycycline therapy was continued in five of these patients and was changed in two patients. In the patients that continued to receive doxycycline the cutaneous side effects gradually improved. Cutaneous side effects of doxycycline should always be a consideration, especially in regions in which brucellosis is endemic and doxycycline is commonly used to treat it.

  19. Evaluation of the Doxycycline Release from AH26 Sealer-Doxycycline Combination: An ex vivo Study

    OpenAIRE

    Ashofteh Yazdi, Kazem; Shokouhinejad, Noushin; Moazeni, Esmaeil; Mirzayi Rad, Sina

    2011-01-01

    INTRODUCTION The purpose of this ex vivo study was to determine the releasing characteristics and doxycycline dentinal diffusion of AH26 sealer-doxycycline combination from apical 3mm of tooth root and apical foramen. MATERIALS AND METHODS One-hundred and two recently extracted single-rooted human teeth were decoronated and prepared with #3 and #4 Gates-Glidden drills and rotary Mtwo files. Smear layer was removed; all surfaces except for apical 3mm of each root were sealed with two coats of ...

  20. Doxycycline-rifampin versus doxycycline-streptomycin in treatment of human brucellosis due to Brucella melitensis. The GECMEI Group. Grupo de Estudio de Castilla-la Mancha de Enfermedades Infecciosas.

    Science.gov (United States)

    Solera, J; Rodríguez-Zapata, M; Geijo, P; Largo, J; Paulino, J; Sáez, L; Martínez-Alfaro, E; Sánchez, L; Sepulveda, M A; Ruiz-Ribó, M D

    1995-09-01

    Brucellosis is a common zoonosis in many parts of the world; the best regimen for the treatment of brucellosis has not been clearly determined. We have carried out a multicenter, open, controlled trial in five general hospitals in Spain to compare the efficacy and safety of doxycycline and rifampin (DR) versus doxycycline and streptomycin (DS) for the treatment of human brucellosis. The study included 194 ambulatory or hospitalized patients with acute brucellosis, without endocarditis or neurobrucellosis. The diagnostic criterion was isolation of Brucella species from blood or other tissues (n = 120) or a standard tube agglutination titer of 1/160 or more for anti-Brucella antibodies with compatible clinical findings (n = 74). Patients were randomly assigned to receive either 100 mg of doxycycline twice daily plus rifampin, 900 mg/day, in a single morning dose for 45 days (DR group) or the same dose of doxycycline for 45 days plus streptomycin, 1 g/day, intramuscularly for 14 days (DS group). A lack of therapeutic efficacy developed in 8 of the 100 patients in the DR group (8%) and in 2 of the 94 patients in the DS group (2%)(P = 0.10). Relapses occurred in 16 of the 100 patients in the DR group (16%) but in only 5 of the 94 patients in the DS group (5.3%) (P = 0.02). When relapse was considered in combination with initial lack of efficacy, 26 patients in the DR group (24%) and 7 patients in the DS group (7.45%) failed to respond to therapy (P = 0.0016). In general, therapy was well tolerated and only four patients (4%) in the DR group and two (2%) in the DS group had episodes of adverse effects necessitating discontinuation of treatment (P> 0.2). We conclude that a doxycycline-and-rifampin regimen is less effective than the doxycycline-and-streptomycin regimen in patients with acute brucellosis.

  1. Doxycycline down-regulates DNA-PK and radiosensitizes tumor initiating cells: Implications for more effective radiation therapy.

    Science.gov (United States)

    Lamb, Rebecca; Fiorillo, Marco; Chadwick, Amy; Ozsvari, Bela; Reeves, Kimberly J; Smith, Duncan L; Clarke, Robert B; Howell, Sacha J; Cappello, Anna Rita; Martinez-Outschoorn, Ubaldo E; Peiris-Pagès, Maria; Sotgia, Federica; Lisanti, Michael P

    2015-06-10

    pharmacokinetics, with nearly 100% oral absorption and a long serum half-life (18-22 hours), at a standard dose of 200-mg per day. In further support of this idea, we show that doxycycline effectively inhibits the mammosphere-forming activity of primary breast cancer samples, derived from metastatic disease sites (pleural effusions or ascites fluid). Our results also have possible implications for the radio-therapy of brain tumors and/or brain metastases, as doxycycline is known to effectively cross the blood-brain barrier. Further studies will be needed to determine if other tetracycline family members also confer radio-sensitivity.

  2. Clinical benefits of incorporating doxycycline into a canine heartworm treatment protocol

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    C. Thomas Nelson

    2017-11-01

    Full Text Available Abstract Background The objective of heartworm treatment is to improve the clinical condition of the patient and to eliminate pre-cardiac, juvenile, and adult worm stages with minimal complications. Pulmonary thromboembolisms are an inevitable consequence of worm death and can result in severe pulmonary reactions and even death of the patient. To minimize these reactions, various treatment protocols involving melarsomine, the only adulticidal drug approved by the US Food and Drug Administrations (FDA, in conjunction with macrocyclic lactone heartworm preventives and glucocorticosteroids have been advocated. The discovery of the bacterial endosymbiont Wolbachia in Dirofilaria immitis has led to several experimental studies examining the effects of administering doxycycline to reduce or eliminate Wolbachia organism. These studies have shown a decrease in gross and microscopic pathology of pulmonary parenchyma in experimental heartworm infections pretreated with doxycycline before melarsomine administration. Methods Electronic medical records from a large veterinary practice in northeast Alabama were searched to identify dogs treated for heartworms with melarsomine from January 2005 through December 2012. The search was refined further to select for dogs that met the following criteria: 1 received two or three doses of ivermectin heartworm preventive prior to melarsomine injections, 2 received one injection of melarsomine followed by two injections 4 to 8 weeks later, and 3 were treated with prednisone following melarsomine injections. The dogs were then divided into those that also were treated with doxycycline 10 mg/kg BID for 4 weeks (Group A, n = 47 and those that did not receive doxycycline (Group B, n = 47. The medical notes of all 94 cases were then reviewed for comments concerning coughing, dyspnea, or hemoptysis in the history, physical exam template, or from telephone conversations with clients the week following each visit. Any

  3. Clinical benefits of incorporating doxycycline into a canine heartworm treatment protocol.

    Science.gov (United States)

    Nelson, C Thomas; Myrick, Elizabeth S; Nelson, Thomas A

    2017-11-09

    The objective of heartworm treatment is to improve the clinical condition of the patient and to eliminate pre-cardiac, juvenile, and adult worm stages with minimal complications. Pulmonary thromboembolisms are an inevitable consequence of worm death and can result in severe pulmonary reactions and even death of the patient. To minimize these reactions, various treatment protocols involving melarsomine, the only adulticidal drug approved by the US Food and Drug Administrations (FDA), in conjunction with macrocyclic lactone heartworm preventives and glucocorticosteroids have been advocated. The discovery of the bacterial endosymbiont Wolbachia in Dirofilaria immitis has led to several experimental studies examining the effects of administering doxycycline to reduce or eliminate Wolbachia organism. These studies have shown a decrease in gross and microscopic pathology of pulmonary parenchyma in experimental heartworm infections pretreated with doxycycline before melarsomine administration. Electronic medical records from a large veterinary practice in northeast Alabama were searched to identify dogs treated for heartworms with melarsomine from January 2005 through December 2012. The search was refined further to select for dogs that met the following criteria: 1) received two or three doses of ivermectin heartworm preventive prior to melarsomine injections, 2) received one injection of melarsomine followed by two injections 4 to 8 weeks later, and 3) were treated with prednisone following melarsomine injections. The dogs were then divided into those that also were treated with doxycycline 10 mg/kg BID for 4 weeks (Group A, n = 47) and those that did not receive doxycycline (Group B, n = 47). The medical notes of all 94 cases were then reviewed for comments concerning coughing, dyspnea, or hemoptysis in the history, physical exam template, or from telephone conversations with clients the week following each visit. Any dog that died within one year of treatment

  4. Doxycycline and its quaternary ammonium derivative for adjuvant therapies of chondrosarcoma.

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    Miladi, Imen; Vivier, Magali; Dauplat, Marie-Mélanie; Chatard, Morgane; Besse, Sophie; Vidal, Aurélien; Chassain, Karine; Jean, Betty; Forestier, Christiane; Chezal, Jean-Michel; Rédini, Francoise; Degoul, Francoise; Miot-Noirault, Elisabeth

    2017-09-01

    This study was conducted during the development of innovative treatment targeting the microenvironment of chondrosarcoma. In this context, MMP inhibitors were conjugated with a quaternary ammonium (QA) function as a targeting ligand to proteoglycans of chondrosarcoma extracellular matrix. Here we report the proof of concept of this strategy applied to the MMP13 inhibitor, doxycycline (Dox). A quaternary ammonium derivative of the MMP13 inhibitor doxycycline (QA-Dox) was synthesized, and its anticancer activity was evaluated in the Swarm rat chondrosarcoma (SRC) model compared with the parent drug doxycycline, in vitro and in vivo. In vivo, dox and QA-Dox efficiency was assessed at equimolar doses according to a q4dx4 schedule by monitoring tumour volume by MRI and PG-targeted scintigraphy. Molecular mechanism (MMP13 expression, proteoglycan level) and histology studies were performed on tumours. The link of QA targeting function to Dox maintained the MMP13 inhibitory activity in vitro. Interestingly, the bacteriostatic activity was lost. SRC cells incubated with both drugs were blocked in S and G2 M phases. Tumour growth inhibition (confirmed by histology) was observed for both Dox and QA-Dox. Undesirable blood effects (leukocyte decrease) were reduced when Dox was targeted to tumour tissue using the QA function. In the SRC model, the MMP13 inhibitor Dox and its QA derivative are promising as adjuvant therapies for chondrosarcoma management.

  5. Comparison between Efficacy of Ciprofioxacin -Doxycycline with Rifampin – Doxycycline Regimens inrelapse of Brucellosis

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    Hossein Sarmadian

    2014-08-01

    Full Text Available Background: Brucellosis is one of the endemic diseases in Iran that has a worldwide spread and is associated with chronic disabilities in humans. Combination therapy of Brucellosis leads to recovery of symptoms, shortening of the symptomatic intervals, and decrease in the rate of relapse and drug resistance. Considering the use of rifampin in the treatment of tuberculosis, and the necessity for an alternative treatment in regions endemic for both tuberculosis and brucellosis, the aim ofthis study was to compare the efficiency of the regimen of rifampin-Doxycycline with ciprofloxacin-Doxycycline in relapse of brucellosis. Materials and methods: This randomized controlled trial was performed on 90 patients, older than 17 years old, affected with brucellosis, which were referred to the Infectious Disease Clinics at ArakUniversity of medical sciences between the years 1384-1387. The patients were randomly divided into two groups: the DR groups, receiving 100 mg of Doxycycline twice a day and 300 mg of rifampin Bid daily for eight weeks and the CD group, receiving 100 mg of Doxycycline plus 500 mg of ciprofloxacin twice a day for eight weeks. The patients were analyzed for the relief of symptoms, drug side effects, and laboratory findings during the treatment. Results:In this study, the rate of relapse in both groups were similar. The relapse was seen in 4.5% and 3.2% of the patients for the DR and CD groups, respectively (P=0.168. The drug side effects were slight in both of groups, with no significant difference, and did not lead to discontinuation of the therapy. Conclusion: According to the same rate of relapse in both CD and DR regimens in the treatment of brucellosis and considering the usage of rifampin in regions with high prevalence of tuberclusis, the CD regimen is recommended as an appropriate one.

  6. The effect of measuring serum doxycycline concentrations on clinical outcomes during treatment of chronic Q fever.

    Science.gov (United States)

    van Roeden, S E; Bleeker-Rovers, C P; Kampschreur, L M; de Regt, M J A; Vermeulen Windsant, A; Hoepelman, A I M; Wever, P C; Oosterheert, J J

    2018-01-08

    First choice treatment for chronic Q fever is doxycycline plus hydroxychloroquine. Serum doxycycline concentration (SDC) >5 μg/mL has been associated with a favourable serological response, but the effect on clinical outcomes is unknown. To assess the effect of measuring SDC during treatment of chronic Q fever on clinical outcomes. We performed a retrospective cohort study, to assess the effect of measuring SDC on clinical outcomes in patients treated with doxycycline and hydroxychloroquine for chronic Q fever. Primary outcome was the first disease-related event (new complication or chronic Q fever-related mortality); secondary outcomes were all-cause mortality and PCR-positivity. Multivariable analysis was performed with a Cox proportional hazards model, with shared-frailty terms for different hospitals included. We included 201 patients (mean age 68 years, 83% male): in 167 patients (83%) SDC was measured, 34 patients (17%) were treated without SDC measurement. First SDC was >5 μg/mL in 106 patients (63%), all with 200 mg doxycycline daily. In patients with SDC measured, dosage was adjusted in 41% (n = 68), concerning an increase in 64 patients. Mean SDC was 4.1 μg/mL before dosage increase, and 5.9 μg/mL afterwards. SDC measurement was associated with a lower risk for disease-related events (HR 0.51, 95% CI 0.26-0.97, P = 0.04), but not with all-cause mortality or PCR-positivity. SDC measurement decreases the risk for disease-related events, potentially through more optimal dosing or improved compliance. We recommend measurement of SDC and striving for SDC >5 μg/mL and <10 μg/mL during treatment of chronic Q fever.

  7. Protective effect of doxycycline on germinal epithelial loss caused by a high-fat diet.

    Science.gov (United States)

    Delgado-Enciso, Ivan; García-Rivera, Alejandro; Madrigal-Pérez, M Violeta M; Rodriguez-Hernandez, Alejandrina; Lugo-Radillo, Agustin; Galvan-Salazar, Hector R; Soriano-Hernández, Alejandro D; Gómez-Tapia, Fernando; Martinez-Martinez, Rafael; Valdez-Velazquez, Laura L; Newton-Sanchez, Oscar A; Gonzalez-Alvarez, Rafael; Rodriguez-Sanchez, Iram P; Melnikov, Valery; Lara-Esqueda, Agustin; Guzman-Esquivel, Jose

    2014-05-01

    A high-fat diet and male obesity are aspects associated with germinal epithelial alterations and male infertility. Some reports have shown that certain tetracyclines can protect the germinal epithelium from toxic drugs. The aim of the present study design was to evaluate the possible effect of doxycycline on testicular germ cells in individuals fed a Western diet (atherogenic), using a murine model. Two groups of male mice (BALB/c) were fed a high-fat Western diet (HFD). One of these two groups was given doxycycline at a dose of 10 mg/kg/day (HFD+Dox). A third group was fed a standard rodent diet (SD group). After 6 months, the mice were euthanized and morphologic and histopathologic analyses were performed. Germinal epithelial height was similar between the SD group (54 μm) and the HFD+Dox group (53 μm) (p = 0.26), and it was significantly reduced in the HFD group (47 μm) (p = 0.0001). The degree of germinal epithelial loss (DGEL) was significantly lower in the SD (10) and HFD+Dox (12.5) groups than in the HFD group (30) (p = 0.0001 and =0.007, respectively). There were no differences in the DGEL between the SD and HFD+Dox groups (p = 0.42). Doxycycline administration was shown to prevent germinal epithelial loss in the testes of mice fed a high-fat diet. Future studies are necessary to evaluate the clinical usefulness of doxycycline or its analogs in persons with a habitual high-fat diet.

  8. Comparative pharmacokinetics of a new oral long-acting formulation of doxycycline hyclate: A canine clinical trial.

    Science.gov (United States)

    Arciniegas Ruiz, Sara Melisa; Gutiérrez Olvera, Lilia; Bernad Bernad, María Josefa; Caballero Chacón, Sara Del Carmen; Vargas Estrada, Dinorah

    2015-12-01

    Doxycicline is used in dogs as treatment of several bacterial infections, mycoplasma, chlamydia and rickettsial diseases. However, it requires long treatments and several doses to be effective. The aim of this study was to determine the pharmacokinetics of four formulations of doxycycline hyclate, administered orally, with different proportions of excipients, acrylic acid-polymethacrylate-based matrices, to obtain longer therapeutic levels than conventional formulation. Forty-eight dogs were randomly assigned in five groups to receive a single oral dose (20mg/kg) of doxycycline hyclate without excipients (control) or a long-acting formulation containing doxycycline, acrylic acid polymer, and polymethacrylate in one of the following four proportions: DOX1(1:0.25:0.0035), DOX2(1:0.5:0.0075), DOX3 (1:1:0.015), or DOX4(1:2:0.0225). Temporal profiles of serum concentrations were obtained at several intervals after each treatment. Therapeutic concentrations were observed for 60h for DOX1 and DOX4, 48h for DOX2 and DOX3 and only 24h for DOX-C. None of the pharmacokinetic parameter differed significantly between DOX1 and DOX2 or between DOX3 and DOX4; however, the findings for the control treatment were significantly different compared to all four long-acting formulations. Results indicated that DOX1 had the most adequate pharmacokinetic-pharmacodynamic relationships for a time-dependent drug and had longer release times than did doxycycline alone. However, all four formulations can be effective depend on the minimum effective serum doxycycline concentration of the microorganism being treated. These results suggest that the use of any of these formulations can reduce the frequency of administration, the patient's stress, occurrence of adverse effects and the cost of treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Occurrence of doxycycline resistant bacteria in the oral cavity after local administration of doxycycline in patients with periodontal disease

    DEFF Research Database (Denmark)

    Larsen, T

    1991-01-01

    Topical antimicrobial treatment is appearing as a means of therapy in patients with advanced periodontal disease. The purpose of the present study was to examine the occurrence of doxycycline resistant bacteria in subgingival plaque and oral cavity after local administration of doxycycline. Five...... patients with advanced marginal periodontitis were scaled, and one approximal pocket in each patient was additionally treated with locally delivered doxycycline. Microbiological samples were obtained from the test site, a contralateral control site and tongue and tonsils before treatment and 3, 13, 26...

  10. Evaluation of the Effect of Probiotic (Inersan®) Alone, Combination of Probiotic with Doxycycline and Doxycycline Alone on Aggressive Periodontitis – A Clinical and Microbiological Study

    OpenAIRE

    Shah, Mishal Piyush; Gujjari, Sheela Kumar; Chandrasekhar, Veerendrakumar Siddhpur

    2013-01-01

    Introduction: The purpose of the present study was to evaluate the effect of a probiotic (Inersan®) alone, a combination of the probiotic with doxycycline and doxycycline alone on aggressive periodontitis patients.

  11. The efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis.

    Science.gov (United States)

    Kong, Fabian Yuh Shiong; Tabrizi, Sepehr N; Fairley, Christopher Kincaid; Vodstrcil, Lenka A; Huston, Wilhelmina M; Chen, Marcus; Bradshaw, Catriona; Hocking, Jane S

    2015-05-01

    There are increasing concerns about treatment failure following treatment for rectal chlamydia with 1 g of azithromycin. A systematic review and meta-analysis was conducted to investigate the efficacy of 1 g of azithromycin as a single dose or 100 mg of doxycycline twice daily for 7 days for the treatment of rectal chlamydia. Medline, Embase, PubMed, Cochrane Controlled Trials Register, Australia New Zealand Clinical Trial Register and ClinicalTrials.gov were searched to the end of April 2014. Studies using 1 g of azithromycin or 7 days of doxycycline for the treatment of rectal chlamydia were eligible. Gender, diagnostic test, serovar, symptomatic status, other sexually transmitted infections, follow-up time, attrition and microbial cure were extracted. Meta-analysis was used to calculate pooled (i) azithromycin and doxycycline efficacy and (ii) efficacy difference. All eight included studies were observational. The random-effects pooled efficacy for azithromycin (based on eight studies) was 82.9% (95% CI 76.0%-89.8%; I(2) = 71.0%; P azithromycin may be considerably lower than 1 week of doxycycline for treating rectal chlamydia. However, the available evidence is very poor. Robust randomized controlled trials are urgently required. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Effects of long-term doxycycline on bone quality and strength in diabetic male DBA/2J mice

    Directory of Open Access Journals (Sweden)

    John L. Fowlkes

    2015-01-01

    Full Text Available In type 1 diabetes, diabetic bone disease (DBD is characterized by decreased bone mineral density, a state of low bone turnover and an increased risk of fracture. Animal models of DBD demonstrate that acquired alterations in trabecular and cortical bone microarchitecture contribute to decreased bone strength in diabetes. With anti-collagenolytic and anti-inflammatory properties, tetracycline derivatives may prevent diabetes-related decreases in bone strength. To determine if doxycycline, a tetracycline class antibiotic, can prevent the development of DBD in a model of long-term diabetes, male DBA/2J mice, with or without diabetes, were treated with doxycycline-containing chow for 10 weeks (dose range, 28–92 mg/kg/day. Long-term doxycycline exposure was not deleterious to the microarchitecture or biomechanical properties of healthy bones in male DBA/2J mice. Doxycycline treatment also did not prevent or alleviate the deleterious changes in trabecular microarchitecture, cortical structure, and biomechanical properties of bone induced by chronic diabetes.

  13. Metabolomic profiling of doxycycline treatment in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Singh, Brajesh; Jana, Saikat K; Ghosh, Nilanjana; Das, Soumen K; Joshi, Mamata; Bhattacharyya, Parthasarathi; Chaudhury, Koel

    2017-01-05

    Serum metabolic profiling can identify the metabolites responsible for discrimination between doxycycline treated and untreated chronic obstructive pulmonary disease (COPD) and explain the possible effect of doxycycline in improving the disease conditions. 1H nuclear magnetic resonance (NMR)-based metabolomics was used to obtain serum metabolic profiles of 60 add-on doxycycline treated COPD patients and 40 patients receiving standard therapy. The acquired data were analyzed using multivariate principal component analysis (PCA), partial least-squares-discriminant analysis (PLS-DA), and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). A clear metabolic differentiation was apparent between the pre and post doxycycline treated group. The distinguishing metabolites lactate and fatty acids were significantly down-regulated and formate, citrate, imidazole and l-arginine upregulated. Lactate and folate are further validated biochemically. Metabolic changes, such as decreased lactate level, inhibited arginase activity and lowered fatty acid level observed in COPD patients in response to add-on doxycycline treatment, reflect the anti-inflammatory action of the drug. Doxycycline as a possible therapeutic option for COPD seems promising. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Effect of cathodic polarization on coating doxycycline on titanium surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Geißler, Sebastian; Tiainen, Hanna; Haugen, Håvard J., E-mail: h.j.haugen@odont.uio.no

    2016-06-01

    Cathodic polarization has been reported to enhance the ability of titanium based implant materials to interact with biomolecules by forming titanium hydride at the outermost surface layer. Although this hydride layer has recently been suggested to allow the immobilization of the broad spectrum antibiotic doxycycline on titanium surfaces, the involvement of hydride in binding the biomolecule onto titanium remains poorly understood. To gain better understanding of the influence this immobilization process has on titanium surfaces, mirror-polished commercially pure titanium surfaces were cathodically polarized in the presence of doxycycline and the modified surfaces were thoroughly characterized using atomic force microscopy, electron microscopy, secondary ion mass spectrometry, and angle-resolved X-ray spectroscopy. We demonstrated that no hydride was created during the polarization process. Doxycycline was found to be attached to an oxide layer that was modified during the electrochemical process. A bacterial assay using bioluminescent Staphylococcus epidermidis Xen43 showed the ability of the coating to reduce bacterial colonization and planktonic bacterial growth. - Highlights: • Titanium hydride was found not to be involved in immobilization of doxycycline. • Doxycycline coating was strongly bound to a modified surface oxide layer. • Effect of coatings tested using a dynamic bacteria assay based on bioluminescence. • Topmost layer of adsorbed doxycycline was shown to have strong antibacterial effect.

  15. Comparison of serological response to doxycycline versus benzathine penicillin G in the treatment of early syphilis in HIV-infected patients: a multi-center observational study.

    Directory of Open Access Journals (Sweden)

    Jen-Chih Tsai

    Full Text Available BACKGROUND: While doxycycline is recommended as an alternative treatment of syphilis in patients with penicillin allergy or intolerance, clinical studies to compare serological response to doxycycline versus benzathine penicillin in treatment of early syphilis among HIV-infected patients remain sparse. METHODS: We retrospectively reviewed the medical records of HIV-infected patients with early syphilis who received doxycycline 100 mg twice daily for 14 days (doxycycline group and those who received 1 dose of benzathine penicillin (2.4 million units (penicillin group between 2007 and 2013. Serological responses defined as a decline of rapid plasma reagin titer by 4-fold or greater at 6 and 12 months of treatment were compared between the two groups. RESULTS: During the study period, 123 and 271 patients in the doxycycline and penicillin group, respectively, completed 6 months or longer follow-up. Ninety-one and 271 patients in the doxycycline and penicillin group, respectively, completed 12 months or longer follow-up. Clinical characteristics were similar between the two groups, except that, compared with penicillin group, doxycycline group had a lower proportion of patients with secondary syphilis (65.4% versus 41.5%, P<0.0001 and a higher proportion of patients with early latent syphilis (25.3% versus 49.6%, P<0.0001. No statistically significant differences were found in the serological response rates to doxycycline versus benzathine penicillin at 6 months (63.4% versus 72.3%, P = 0.075 and 12 months of treatment (65.9% versus 68.3%, P = 0.681. In multivariate analysis, secondary syphilis, but not treatment regimen, was consistently associated with serological response at 6 and 12 months of follow-up. CONCLUSIONS: The serological response rates to a 14-day course of doxycycline and a single dose of benzathine penicillin were similar in HIV-infected patients with early syphilis at 6 and 12 months of follow-up. Patients with secondary

  16. Doxycycline potentiates antitumor effect of 5-aminolevulinic acid-mediated photodynamic therapy in malignant peripheral nerve sheath tumor cells.

    Science.gov (United States)

    Lee, Ming-Jen; Hung, Shih-Hsuan; Huang, Mu-Ching; Tsai, Tsuimin; Chen, Chin-Tin

    2017-01-01

    Neurofibromatosis type 1 (NF1) is one of the most common neurocutaneous disorders. Some NF1 patients develop benign large plexiform neurofibroma(s) at birth, which can then transform into a malignant peripheral nerve sheath tumor (MPNST). There is no curative treatment for this rapidly progressive and easily metastatic neurofibrosarcoma. Photodynamic therapy (PDT) has been developed as an anti-cancer treatment, and 5-aminolevulinic (ALA) mediated PDT (ALA-PDT) has been used to treat cutaneous skin and oral neoplasms. Doxycycline, a tetracycline derivative, can substantially reduce the tumor burden in human and animal models, in addition to its antimicrobial effects. The purpose of this study was to evaluate the effect and to investigate the mechanism of action of combined doxycycline and ALA-PDT treatment of MPNST cells. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the combination of ALA-PDT and doxycycline significantly reduce MPNST survival rate, compared to cells treated with each therapy alone. Isobologram analysis showed that the combined treatment had a synergistic effect. The increased cytotoxic activity could be seen by an increase in cellular protoporphyrin IX (PpIX) accumulation. Furthermore, we found that the higher retention of PpIX was mainly due to increasing ALA uptake, rather than activity changes of the enzymes porphobilinogen deaminase and ferrochelatase. The combined treatment inhibited tumor growth in different tumor cell lines, but not in normal human Schwann cells or fibroblasts. Similarly, a synergistic interaction was also found in cells treated with ALA-PDT combined with minocycline, but not tetracycline. In summary, doxycycline can potentiate the effect of ALA-PDT to kill tumor cells. This increased potency allows for a dose reduction of doxycycline and photodynamic radiation, reducing the occurrence of toxic side effects in vivo.

  17. Doxycycline potentiates antitumor effect of 5-aminolevulinic acid-mediated photodynamic therapy in malignant peripheral nerve sheath tumor cells.

    Directory of Open Access Journals (Sweden)

    Ming-Jen Lee

    Full Text Available Neurofibromatosis type 1 (NF1 is one of the most common neurocutaneous disorders. Some NF1 patients develop benign large plexiform neurofibroma(s at birth, which can then transform into a malignant peripheral nerve sheath tumor (MPNST. There is no curative treatment for this rapidly progressive and easily metastatic neurofibrosarcoma. Photodynamic therapy (PDT has been developed as an anti-cancer treatment, and 5-aminolevulinic (ALA mediated PDT (ALA-PDT has been used to treat cutaneous skin and oral neoplasms. Doxycycline, a tetracycline derivative, can substantially reduce the tumor burden in human and animal models, in addition to its antimicrobial effects. The purpose of this study was to evaluate the effect and to investigate the mechanism of action of combined doxycycline and ALA-PDT treatment of MPNST cells. An 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay showed that the combination of ALA-PDT and doxycycline significantly reduce MPNST survival rate, compared to cells treated with each therapy alone. Isobologram analysis showed that the combined treatment had a synergistic effect. The increased cytotoxic activity could be seen by an increase in cellular protoporphyrin IX (PpIX accumulation. Furthermore, we found that the higher retention of PpIX was mainly due to increasing ALA uptake, rather than activity changes of the enzymes porphobilinogen deaminase and ferrochelatase. The combined treatment inhibited tumor growth in different tumor cell lines, but not in normal human Schwann cells or fibroblasts. Similarly, a synergistic interaction was also found in cells treated with ALA-PDT combined with minocycline, but not tetracycline. In summary, doxycycline can potentiate the effect of ALA-PDT to kill tumor cells. This increased potency allows for a dose reduction of doxycycline and photodynamic radiation, reducing the occurrence of toxic side effects in vivo.

  18. An Optimized Lock Solution Containing Micafungin, Ethanol and Doxycycline Inhibits Candida albicans and Mixed C. albicans – Staphyloccoccus aureus Biofilms

    Science.gov (United States)

    Lown, Livia; Peters, Brian M.; Walraven, Carla J.; Noverr, Mairi C.; Lee, Samuel A.

    2016-01-01

    Candida albicans is a major cause of catheter-related bloodstream infections and is associated with high morbidity and mortality. Due to the propensity of C. albicans to form drug-resistant biofilms, the current standard of care includes catheter removal; however, reinsertion may be technically challenging or risky. Prolonged exposure of an antifungal lock solution within the catheter in conjunction with systemic therapy has been experimentally attempted for catheter salvage. Previously, we demonstrated excellent in vitro activity of micafungin, ethanol, and high-dose doxycycline as single agents for prevention and treatment of C. albicans biofilms. Thus, we sought to investigate optimal combinations of micafungin, ethanol, and/or doxycycline as a lock solution. We performed two- and three-drug checkerboard assays to determine the in vitro activity of pairwise or three agents in combination for prevention or treatment of C. albicans biofilms. Optimal lock solutions were tested for activity against C. albicans clinical isolates, reference strains and polymicrobial C. albicans-S. aureus biofilms. A solution containing 20% (v/v) ethanol, 0.01565 μg/mL micafungin, and 800 μg/mL doxycycline demonstrated a reduction of 98% metabolic activity and no fungal regrowth when used to prevent fungal biofilm formation; however there was no advantage over 20% ethanol alone. This solution was also successful in inhibiting the regrowth of C. albicans from mature polymicrobial biofilms, although it was not fully bactericidal. Solutions containing 5% ethanol with low concentrations of micafungin and doxycycline demonstrated synergistic activity when used to prevent monomicrobial C. albicans biofilm formation. A combined solution of micafungin, ethanol and doxycycline is highly effective for the prevention of C. albicans biofilm formation but did not demonstrate an advantage over 20% ethanol alone in these studies. PMID:27428310

  19. Doxycyclin induced esophageal injury: A Case series

    Directory of Open Access Journals (Sweden)

    İsmail Demiryılmaz

    2013-01-01

    Full Text Available Some drugs have been known to damage to esophagusfor a long time. Half of the cases reported are of tetracyclineand its derivatives. The damage caused by thesedrugs is depends on the drug itself and the patient.In this paper we present 5 patients having diagnosedesophageal damage endoscopically after due to doxycyclinuse. The mean age of the patients was 26 years.Three of them for acne and 2 for heir complaints gynecologicalinfection were taking these drugs. Lesions werelocated at the middle in 4 cases and lover part in 1 patient.The common complaint was retrosternal pain and heartburnafter taking the drug with insufficient water or withoutwater. All the patients were relieved by symtomatic teratment.Esophageal damage is to be remembered in patientscomplaning sudden pain and difficult swallowing on doxycyclintreatment and endoscopic procedure should beemployed for definition of diagnosis and evaluation of theseverity of the damage. After treatment, endoscopic controlis not necessary. Physicians must not forget to advicethe patients to take these drugs with splendid amount ofwater.Key words: Doxycycline, esophagus damage, endoscopy

  20. Doxycycline administration improves fascial interface in hernia repair.

    Science.gov (United States)

    Tharappel, Job C; Bower, Curtis E; Whittington Harris, Jennifer; Ramineni, Sandeep K; Puleo, David A; Roth, J Scott

    2014-08-01

    Despite improvements in ventral hernia repair techniques, their recurrence rates are unacceptably high. Increased levels of matrix metalloproteinases (MMPs) and reduced collagen-1 to -3 ratios are implicated in incisional hernia formation. We have recently shown doxycycline treatment for 4 wk after hernia repair reduced MMP levels, significantly increased collagen-1 to -3 ratios, and increased tensile strength of repaired interface fascia. However, this increase was not statistically significant. In this study, we extended treatment duration to determine whether this would impact the tensile strength of the repaired interface fascia. Thirty-two male Sprague-Dawley rats underwent incision hernia creation and subsequent repair with polypropylene mesh. The animals received either saline (n = 16) or doxycycline (n = 16) beginning from 1 day before hernia repair until the end of survival time of 6 wk (n = 16) or 12 wk (n = 16). Tissue samples were investigated for MMPs and collagen subtypes using Western blot procedures, and tensiometric analysis was performed. At both 6 and 12 wk after hernia repair, the tensiometric strength of doxycycline-treated mesh to fascia interface (MFI) tissue showed a statistically significant increase when compared with untreated control MFI. In both groups, collagen-1, -2, and -3 ratios were remarkably increased in doxycycline-treated MFI. At 6 wk, the doxycycline-treated MFI group showed a significant decrease in MMP-2, an increase in MMP-3, and no change in MMP-9. At 12 wk, MMP-9 showed a remarkable reduction, whereas MMP-2 and -3 protein levels increased in the doxycycline-treated MFI group. Doxycycline administration results in significantly improved strength of repaired fascial interface tissue along with a remarkable increase in collagen-1, -2, and -3 ratios. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Efficacy of Doxycycline in the Treatment of Syphilis.

    Science.gov (United States)

    Dai, Ting; Qu, Rui; Liu, Jinfen; Zhou, Pingyu; Wang, Qianqiu

    2017-01-01

    Doxycycline is an alternative antibiotic drug for the treatment of syphilis, but data on its efficacy, especially data on its efficacy against late latent syphilis, are limited. A retrospective study was conducted to evaluate the effectiveness of doxycycline for the treatment of patients with different stages of syphilis. Patients who received doxycycline treatment between June 2011 and June 2014 were involved. The serological response to doxycycline was defined as either a negative toluidine red unheated serum test (TRUST) result or a ≥4-fold decrease in titer at 12 months following the treatment. Univariate and multivariate logistic regression analyses were performed to identify factors associated with the serological response. During the study period, a total of 163 syphilis patients were treated with doxycycline, and 118 patients completed doxycycline treatment and the 12-month follow-up. Among the 118 patients, the serological response rate at 12 months was 100.0% (7/7) in patients with primary syphilis, 96.9% (62/64) in patients with secondary syphilis, 91.3% (21/23) in patients with early latent syphilis, and 79.2% (19/24) in patients with late latent syphilis. The total serological response rates were 92.4% (109/118) for preprotocol (PP) patients and 66.9% (109/163) for all intention-to-treat (ITT) patients. In multivariate analysis, patients who serologically responded at 12 months following treatment were positively associated with a higher baseline TRUST titer and an earlier syphilis stage than nonresponders. Our study showed excellent treatment outcomes in patients with different stages of syphilis. Our data, along with those from other reports, support the usage of doxycycline as a good alternative therapeutic option in the treatment of syphilis. Copyright © 2016 American Society for Microbiology.

  2. Investigation of Polycaprolactone Matrices for Intravaginal Delivery of Doxycycline.

    Science.gov (United States)

    Pathak, Meenakshi; Coombes, Allan G A; Turner, Mark S; Palmer, Cheryn; Wang, Dongjie; Steadman, Kathryn J

    2015-12-01

    Polycaprolactone (PCL) matrices loaded with doxycycline were produced by rapidly cooling suspensions of the drug powder in PCL solution in acetone. Drug loadings of 5%, 10%, and 15% (w/w) of the PCL content were achieved. Exposure of doxycycline powder to matrix processing conditions in the absence of PCL revealed an endothermic peak at 65°C with the main peak at 167°C, suggesting solvatomorph formation. Rapid "burst release" of 24%-32% was measured within 24 h when matrices were immersed in simulated vaginal fluid (SVF) at 37°C, because of the presence of drug at or close to the matrix surface, which is further confirmed by scanning electron microscopy. Gradual release of 66%-76% of the drug content occurred over the following 14 days. SVF containing doxycycline released from drug-loaded PCL matrices retained 81%-90% antimicrobial activity compared with the nonformulated drug. The concentrations of doxycycline predicted to be released into vaginal fluid from a PCL matrix in the form of an intravaginal ring would be sufficient to kill Neisseria gonorrhoea and many other pathogens. These results indicate that PCL may be a suitable polymer for controlled intravaginal delivery of doxycycline for the treatment of sexually transmitted infections. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  3. Doxycycline reduces cardiac matrix metalloproteinase-2 activity but does not ameliorate myocardial dysfunction during reperfusion in coronary artery bypass patients undergoing cardiopulmonary bypass.

    Science.gov (United States)

    Schulze, Costas J; Castro, Michele M; Kandasamy, Arulmozhi D; Cena, Jonathan; Bryden, Courtney; Wang, Shoa H; Koshal, Arvind; Tsuyuki, Ross T; Finegan, Barry A; Schulz, Richard

    2013-11-01

    doxycycline group (p = 0.05). Doxycycline, however, did not ameliorate cardiac mechanical dysfunction following reperfusion or the cardiopulmonary bypass-coronary artery bypass graft-induced increased plasma matrix metalloproteinase-9, interleukin-6, and C-reactive protein levels. Cardiopulmonary bypass-coronary artery bypass graft or doxycycline did not change tissue or plasma troponin I levels at 10 minutes reperfusion. Although doxycycline did not improve myocardial stunning following coronary artery bypass graft surgery with cardiopulmonary bypass, it reduced cardiac matrix metalloproteinase-2 activity in these patients. A larger trial and/or higher dose of doxycycline may yet be warranted.

  4. Doxycycline induced photodamage to human neutrophils and tryptophan

    Energy Technology Data Exchange (ETDEWEB)

    Sandberg, S.; Glette, J.; Hopen, G.; Solberg, C.O. (Haukeland Sykehus, Bergen (Norway))

    1984-01-01

    Neutrophil function were studied following irradiation (340-380 nm) of the cells in the presence of 22 ..mu..M doxycycline. At increasing light fluence the locomotion, chemiluminescence and glucose oxidation (by the hexose monophosphate shunt) of the neutrophils steadily decreased. The photodamage increased with increasing preincubation temperature and time and was enhanced in D/sub 2/O, reduced in azide and abolished in anaerobiosis. Superoxide dismutase, catalase or mannitol did not influence the photodamage. Photooxidation of tryptophan in the presence of doxycycline was increased 9-10-fold in D/sub 2/O and nearly abolished in the presence of 0.25 mM NaN/sub 3/, indicating that singlet oxygen is the most important reactive oxygen species in the doxycycline-induced photodamage. The results may explain some of the features of tetracycline-induced photosensitivity and why other authors have obtained diverging results when studying the influence of tetracyclines on neutrophil functions.

  5. 76 FR 72935 - Amended Authorization of Emergency Use of Doxycycline Hyclate Tablet Emergency Kits for Eligible...

    Science.gov (United States)

    2011-11-28

    ... HUMAN SERVICES Food and Drug Administration Amended Authorization of Emergency Use of Doxycycline... Authorization) for doxycycline hyclate tablet emergency kits for eligible United States Postal Service (USPS... doxycycline hyclate tablets accompanied by emergency use information subject to the terms of any authorization...

  6. 75 FR 61489 - Renewal of Declaration Regarding Emergency Use of Doxycycline Hyclate Tablets Accompanied by...

    Science.gov (United States)

    2010-10-05

    ... HUMAN SERVICES Office of the Secretary Renewal of Declaration Regarding Emergency Use of Doxycycline... use of doxycycline hyclate tablets accompanied by emergency use information subject to the terms of..., Michael O. Leavitt, declared an emergency justifying the authorization of the emergency use of doxycycline...

  7. Extensive Darier Disease Successfully Treated with Doxycycline Monotherapy

    Directory of Open Access Journals (Sweden)

    Alicia Sfecci

    2015-10-01

    Full Text Available Darier disease (DD is a rare dominantly inherited genodermatosis characterized by loss of intercellular adhesion (acantholysis and abnormal keratinization. DD is often difficult to manage. Numerous treatments have reportedly been used for the treatment of DD, with limited success. Systemic retinoids are considered the drug of choice for treating DD. However, their use is limited by potential deleterious side effects. Considering the recently reported efficacy of doxycycline for Hailey-Hailey disease, an inherited acantholytic skin disorder pathogenetically similar to DD, we report the case of a patient with extensive DD who showed a dramatic response to oral doxycycline monotherapy.

  8. Pharmacokinetic depletion phase of doxycycline in healthy and Mycoplasma gallisepticum-infected chicken broilers after coadministration of enrofloxacin traces.

    Science.gov (United States)

    Gbylik-Sikorska, M; Gajda, A; Posyniak, A

    2017-07-04

    The objective of this study was to investigate the influence of enrofloxacin (ENR) traces on doxycycline (DC) pharmacokinetic depletion phase parameters in plasma and lungs of healthy and Mycoplasma gallisepticum (MG)-infected chicken broilers. The multiple-dose oral administration of DC to chickens which were permanently exposed on ENR traces significantly increased concentration of DC in plasma and lung. It also prolonged the DC elimination time in both healthy and infected animals after final dose. The obtained result indicated that simultaneous administration of DC and ENR in chicken broilers therapy should be avoided. © 2017 John Wiley & Sons Ltd.

  9. Doxycycline levels and anti-Wolbachia antibodies in sera from dogs experimentally infected with Dirofilaria immitis and treated with a combination of ivermectin/doxycycline.

    Science.gov (United States)

    Menozzi, A; Bertini, S; Turin, L; Serventi, P; Kramer, L; Bazzocchi, C

    2015-04-30

    Sera from Dirofilaria immitis-experimentally infected dogs treated with a combination of ivermectin/doxycycline were analysed for doxycycline levels by HPLC and anti-Wolbachia Surface Protein (rWSP) antibodies by ELISA and compared with sera from dogs treated with doxycycline alone. Results show that doxycycline levels were not statistically different between the two groups. Circulating anti-WSP antibody titres were markedly lower in both treatment groups when compared to control D. immitis infected dogs, indicating that doxycycline is able to reduce Wolbachia and prevent the immune response against the bacteria. The combination treatment protocol has been shown to be highly adulticidal and further studies are needed to better understand the interaction between doxycycline and ivermectin in D. immitis infected dogs. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Doxycycline exerted neuroprotective activity by enhancing the activation of neuropeptide GPCR PAC1.

    Science.gov (United States)

    Yu, Rongjie; Zheng, Lijun; Cui, Yue; Zhang, Huahua; Ye, Heng

    2016-04-01

    Doxycycline has significant neuroprotective effect with anti-inflammatory and anti-apoptotic activity. We found for the first time that doxycycline specially promoted the proliferation of Chinese hamster ovary (CHO) cells with high expression of neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) preferring G protein-coupled receptor (GPCR), PACAP receptor 1(PAC1) and induced the internalization of PAC1 tagged with yellow fluorescent protein (YFP) indicating doxycycline interacted with PAC1. The homology modeling of PAC1 and molecular docking of doxycycline with PAC1 showed the theoretical binding of doxycycline to PAC1 at the site where PACAP(30-37) recognized. The competition binding assay and PAC1 site-specific mutation of Asp116, which formed two hydrogen bonds with Dox, confirmed the binding of doxycycline to PAC1 imitating PACAP(30-37). Doxycycline (100 ng/mL) significantly promoted the proliferative activities of vasoactive intestinal polypeptide (VIP) and oligopeptide HSDGIF responsible for the activation of PAC1 in PAC1-CHO cells, indicating that doxycycline facilitated the binding and the activation of PAC1 imitating PACAP(28-38). In Neuro2a cells with endogenous expression of PAC1 and its ligands, doxycycline not only promoted the proliferation of Neuro2a cells but also protected the cells from scopolamine induced apoptosis, which was inhibited by cAMP-PKA signal pathway inhibitor H-89, PAC1 shRNA or PACAP antagonist PACAP(6-38). The in vivo study showed long-term treatment with doxycycline (100ug/kg) had significant effect against scopolamine induced amnesia, and the synergetic anti-apoptotic, anti-oxidative and neuroprotective effect of doxycycline with VIP was more efficient than doxycycline alone or VIP alone, indicating doxycycline enhanced the activation of PAC1 in vivo effectively. Furthermore, doxycycline analogue minocycline also had similar theoretically binding site on PAC1 to doxycycline and displayed corresponding

  11. Effect of Process Factors on the Properties of Doxycycline ...

    African Journals Online (AJOL)

    HP

    Purpose: To develop and evaluation ascorbyl palmitate niosomes in order to achieve a transdermal and/or systemic nanocarier of doxycycline. Methods: Vesicles were formed from ascorbyl palmitate in combination with cholesterol and a negatively charged lipid, dicetyl phosphate. Niosomes were prepared by film hydration ...

  12. A Comparison Between Doxycycline and Ampicillin in the treatment ...

    African Journals Online (AJOL)

    A Comparison Between Doxycycline and Ampicillin in the treatment of Bronchopneumonia complicating measles. I.R. Lang ... differences in the duration of pyrexia and consolidation are discussed and various conclusions drawn. The results did not correspond with sensitivity tests conducted on swabs taken on admission.

  13. A COMPARISON BETWEEN DOXYCYCLINE Mm AMPICILLl I THE ...

    African Journals Online (AJOL)

    1971-07-03

    Jul 3, 1971 ... Fifty-nine cases of measles with bronchopneumonia as a complication were treated with e'ther doxycycline or am- picillin. The differences in the duration of pyrexia and. consolidaTion are d'scussed and various conclusions drml"ll. The results did not correspond with sensitivity tests CO!1- ducted on swabs ...

  14. Doxycycline inhibits collagen synthesis by bovine chondrocytes cultured in alginate

    NARCIS (Netherlands)

    Beekman, B.; Verzijl, N.; Roos, J.A.D.M.de; Koopman, J.L.; Tekoppele, J.M.

    1997-01-01

    Doxycycline is known for its ability to inhibit matrix metalloproteinases (MMPs), a family of enzymes that play a role in cartilage breakdown in arthritides. Its prophylactic effect in reducing joint degradation in osteoarthritis is mainly attributed to this property. In this study, we show that

  15. Delayed Microbial Cure of Lymphogranuloma Venereum Proctitis with Doxycycline Treatment

    NARCIS (Netherlands)

    de Vries, H.J.C.; Smelov, V.; Middelburg, J.G.; Pleijster, J.; Speksnijder, A.G.; Morré, S.A.

    2009-01-01

    Microbial cure of chlamydia proctitis (lymphogranuloma venereum [LGV] and non-LGV) with doxycycline treatment was evaluated by chlamydia DNA and RNA persistence in anal swab specimens. In LGV proctitis, RNA persisted for up to 16 days. In non-LGV chlamydia proctitis, DNA was undetectable after 7

  16. Doxycycline Attenuates Endotoxin-Induced Uveitis by Prostaglandin E2-EP4 Signaling.

    Science.gov (United States)

    Huang, Jingwen; Su, Wenru; Chen, Xiaoqing; Cheng, Xiaokang; Dai, Ye; Han, Longhui; Liang, Dan

    2015-10-01

    We explored the anti-inflammatory effects of doxycycline in experimental uveitis and the underlying mechanisms. Rats with endotoxin-induced uveitis (EIU) received doxycycline (1.5 mg/kg) or the control vehicle via intraperitoneal injection. Clinical scores were graded under a slit lamp. Rat peritoneal macrophages were used in vitro to further explore the anti-inflammatory mechanisms of doxycycline. The levels of nitric oxide (NO), TNF-α, IL-1β, prostaglandin E2 (PGE2), cyclooxygenase (COX)-2, I kappa B-α (IκB-α), inducible nitric oxide synthase (iNOS), Akt, caspase-3, and nuclear factor-kappa B (NF-κB) were analyzed. Treatment with doxycycline dramatically reduced the clinical scores of EIU (P doxycycline significantly inhibited the production of NO, IL-1β, and TNF-α in peritoneal macrophages by modulating the PI3K/Akt/IκB-α/NF-κB pathway. Importantly, we found that doxycycline significantly enhanced COX2 expression and PGE2 production both in vivo and in vitro. More importantly, blockade of the EP4 receptor of PGE2 significantly reversed the doxycycline-mediated inhibition of macrophages and the PI3K/Akt pathway in vitro. Furthermore, simultaneous injection of an EP4 antagonist and doxycycline significantly blocked the doxycycline-mediated attenuation of EIU. Doxycycline can ameliorate EIU, and PGE2-EP4 signaling is essential for the anti-inflammatory effects of doxycycline in vitro and in vivo.

  17. Antibody/doxycycline combined therapy for pulmonary ricinosis: Attenuation of inflammation improves survival of ricin-intoxicated mice

    Directory of Open Access Journals (Sweden)

    Yoav Gal

    2014-01-01

    Full Text Available Ricin, a highly toxic plant-derived toxin, is considered a potential weapon in biological warfare due to its high availability and ease of preparation. Pulmonary exposure to ricin results in the generation of an acute edematous inflammation followed by respiratory insufficiency and death. Passive immunization with polyclonal anti-ricin antibodies conferred protection against pulmonary ricinosis, however, at clinically-relevant time points for treatment, survival rates were limited. In this study, intranasal instillation of a lethal dose of ricin to mice, served as a lung challenge model for the evaluation and comparison of different therapeutic modalities against pulmonary ricinosis. We show that treatment with doxycycline resulted in a significant reduction of pro-inflammatory cytokines, markers of oxidative stress and capillary permeability in the lungs of the mice. Moreover, survival rates of mice intoxicated with ricin and treated 24 h later with anti-ricin antibody were significantly improved by co-administration of doxycycline. In contrast, co-administration of the steroid drug dexamethasone with anti-ricin antibodies did not increase survival rates when administered at late hours after intoxication, however dexamethasone did exert a positive effect on survival when applied in conjunction with the doxycycline treatment. These studies strongly suggest that combined therapy, comprised of neutralizing anti-ricin antibodies and an appropriate anti-inflammatory agent, can promote high-level protection against pulmonary ricinosis at clinically-relevant time points post-exposure.

  18. Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis

    Science.gov (United States)

    Sharma, Raman; Jayoussi, Ghaith Al; Tyrer, Hayley E.; Gamble, Joanne; Hayward, Laura; Guimaraes, Ana F.; Davies, Jill; Waterhouse, David; Cook, Darren A. N.; Myhill, Laura J.; Clare, Rachel H.; Cassidy, Andrew; Steven, Andrew; Johnston, Kelly L.; Ford, Louise; Turner, Joseph D.; Ward, Stephen A.; Taylor, Mark J.

    2016-01-01

    Lymphatic filariasis and onchocerciasis are parasitic helminth diseases, which cause severe morbidities such as elephantiasis, skin disease and blindness, presenting a major public health burden in endemic communities. The anti-Wolbachia consortium (A·WOL: http://www.a-wol.com/) has identified a number of registered antibiotics that target the endosymbiotic bacterium, Wolbachia, delivering macrofilaricidal activity. Here we use pharmacokinetics/pharmacodynamics (PK/PD) analysis to rationally develop an anti-Wolbachia chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-Wolbachia efficacy in a murine Brugia malayi model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25–40 mg/Kg regimen is bioequivalent to a clinically effective 100–200 mg/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes Wolbachia more effectively than doxycycline (99.51% vs. 90.35%) after 28 day 25 mg/Kg bid regimens with a more potent block in microfilarial production. PK/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis. PMID:26996237

  19. The Inhibitory Effect of Doxycycline on Cisplatin-Sensitive and -Resistant Epithelial Ovarian Cancer

    Science.gov (United States)

    Ma, Bei; Xu, Ming-juan

    2014-01-01

    Background Detecting a new effective and hypotoxic anticancer drug is an emerging new strategy for cancer chemotherapy. Doxycycline (DC) is a kind of antibiotics but also inhibits tumorigenesis. Methods MTT and cell invasion assay, flow cytometry, western-blot analysis and nude mice were used to investigate the effects and underlying mechanisms of doxycycline on epithelial ovarian cancer cells. Results Doxycycline inhibited the proliferation and invasion of SKOV3 and SKOV3/DDP; induced moderate apoptosis of SKOV3/DDP. CXCR4 expression at both mRNA and protein levels was downregulated in both cell lines when treated with doxycycline. Akt and ERK1/2 were involved in doxycycline effect on cell proliferation of SKOV3 but not of SKOV3/DDP. Akt and EKR1/2 phosphorylation were activated by SDF-1α, which was then inhibited by doxycycline in SKOV3. Pro-caspase-3 expression was significantly higher in SKOV3 than that in SKOV3/DDP which was upregulated when treated with doxycycline. In vivo, doxycycline inhibited peritoneal tumor xenograft and decreased malignant ascites. Conclusion Doxycycline not only has an inhibitory effect on ovarian cancer, but also can increase sensitivity to cisplatin. SDF-1α/CXCR4-regulated Akt and ERK 1/2 activations are probably involved in the antitumor effect of doxycycline on SKOV3 cells, while upregulation of pro-caspase-3 may be the main mechanism involved in SKOV3/DDP cells. PMID:24598933

  20. Clinical trial of doxycycline for matrix metalloproteinase-9 inhibition in patients with an abdominal aneurysm doxycycline selectively depletes aortic wall neutrophils and cytotoxic t cells

    NARCIS (Netherlands)

    Lindeman, J.H.N.; Abdul-Hussien, H.; Bockel, J.H. van; Wolterbeek, R.; Kleemann, R.

    2009-01-01

    Background-Doxycycline has been shown to effectively inhibit aneurysm formation in animal models of abdominal aortic aneurysm. Although this effect is ascribed to matrix metalloproteinase-9 inhibition, such an effect is unclear in human studies. We reevaluated the effect of doxycycline on aortic

  1. Use of doxycycline for leptospirosis after high-risk exposure in São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Claudio R. GONSALEZ

    1998-01-01

    Full Text Available A clinical trial pilot study, double-blinded, randomized, and controlled with a placebo to assess the effectiveness of oral doxycycline (200 mg, single dose in preventing leptospirosis after high exposure to potentially contamined water was performed in São Paulo, SP, Brazil. Confirmed cases were defined as those with leptospira IgM antibody and symptoms; asymptomatic cases were those presenting with IgM antibodies but no symptoms; and suspected cases were individuals with symptoms but no IgM antibody. Forty subjects were given doxycycline and 42 were given placebo. In the drug-treated group there were 2 confirmed cases, 11 asymptomatic cases, and 6 suspected cases. In the placebo group there were 5 confirmed, 6 symptomatic, and 5 suspected cases. Even though we found a protective association of doxycycline for confirmed leptospirosis cases (RR = 2.3 and seroconversion only (RR = 2.0, the association was not statistically significant because of the small number of individuals enrolled in this pilot study. We observed that the 22% of the volunteers already had IgM antibodies to leptospirosis at the first sampling. Finally, the attack rate to confirmed, asymptomatic, and suspected cases of Leptospirosis was 8.5%, 22%, and 13%, respectively, in this population.Um ensaio clínico, duplo-cego, ao acaso, e controlado com placebo para aferir a eficácia da doxiciclina (200 mg, dose única em prevenir leptospirose após exposição de alto risco com água potencialmente contaminada foi realizado em São Paulo, SP, Brasil. Casos confirmados foram definidos como aqueles que apresentavam anticorpos IgM anti-Leptospira e sintomas; casos assintomáticos eram aqueles que apresentavam somente anticorpo IgM, casos suspeitos apresentavam sintomas, porém sem anticorpo IgM. 40 indivíduos tomaram doxaciclina e 42 tomaram placebo. No grupo tratado houve 2 casos confirmados, 11 assintomáticos e 6 casos suspeitos. No grupo placebo houve 5 casos confirmados, 6

  2. Influence of Mycotoxin Binders on the Oral Bioavailability of Doxycycline in Pigs.

    Science.gov (United States)

    De Mil, Thomas; Devreese, Mathias; De Saeger, Sarah; Eeckhout, Mia; De Backer, Patrick; Croubels, Siska

    2016-03-16

    Mycotoxin binders are feed additives that aim to adsorb mycotoxins in the gastrointestinal tract of animals, making them unavailable for systemic absorption. The antimicrobial drug doxycycline (DOX) is often used in pigs and is administered through feed or drinking water; hence, DOX can come in contact with mycotoxin binders in the gastrointestinal tract. This paper describes the effect of four mycotoxin binders on the absorption of orally administered DOX in pigs. Two experiments were conducted: The first used a setup with bolus administration to fasted pigs at two different dosages of mycotoxin binder. In the second experiment, DOX and the binders were mixed in the feed at dosages recommended by the manufacturers (= field conditions). Interactions are possible between some of the mycotoxin binders dosed at 10 g/kg feed but not at 2 g/kg feed. When applying field conditions, no influences were seen on the plasma concentrations of DOX.

  3. Thermodynamic studies of iron chelation with doxycycline in acidic medium

    Science.gov (United States)

    Javed, Javeria; Zahir, Erum

    2017-06-01

    Doxycycline (DOX) is a broad-spectrum tetracycline antibiotic synthetically derived from oxytetracycline. The complex formation of this drug with iron(III) was studied using spectrophotometry. The thermodynamic parameters of the systems were calculated using the changes in the absorption spectra which occur due to hydrogen bond or complex formation. Thermodynamic parameters of the formation of iron(III) complex with doxycycline (Δ H, Δ G, Δ S, and stability constants) were determined spectrophotometrically at a wavelength corresponding to absorption maximum (374.5 nm) at three different temperatures (22, 35, and 45°C). The obtained data show that the complex has metal to ligand molar ratio of 1: 2 at pH 2-3. The stability constants were calculated to be 13.99 × 106, 7.06 × 105, and 1.29 × 106 by mole ratio method at 22, 35, and 45°C, respectively.

  4. A doxycycline-loaded polymer-lipid encapsulation matrix coating for the prevention of implant-related osteomyelitis due to doxycycline-resistant methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Metsemakers, Willem-Jan; Emanuel, Noam; Cohen, Or; Reichart, Malka; Potapova, Inga; Schmid, Tanja; Segal, David; Riool, Martijn; Kwakman, Paulus H S; de Boer, Leonie; de Breij, Anna; Nibbering, Peter H; Richards, R Geoff; Zaat, Sebastian A J; Moriarty, T Fintan

    2015-07-10

    Implant-associated bone infections caused by antibiotic-resistant pathogens pose significant clinical challenges to treating physicians. Prophylactic strategies that act against resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), are urgently required. In the present study, we investigated the efficacy of a biodegradable Polymer-Lipid Encapsulation MatriX (PLEX) loaded with the antibiotic doxycycline as a local prophylactic strategy against implant-associated osteomyelitis. Activity was tested against both a doxycycline-susceptible (doxy(S)) methicillin-susceptible S. aureus (MSSA) as well as a doxycycline-resistant (doxy(R)) methicillin-resistant S. aureus (MRSA). In vitro elution studies revealed that 25% of the doxycycline was released from the PLEX-coated implants within the first day, followed by a 3% release per day up to day 28. The released doxycycline was highly effective against doxy(S) MSSA for at least 14days in vitro. A bolus injection of doxycycline mimicking a one day release from the PLEX-coating reduced, but did not eliminate, mouse subcutaneous implant-associated infection (doxy(S) MSSA). In a rabbit intramedullary nail-related infection model, all rabbits receiving a PLEX-doxycycline-coated nail were culture negative in the doxy(S) MSSA-group and the surrounding bone displayed a normal physiological appearance in both histological sections and radiographs. In the doxy(R) MRSA inoculated rabbits, a statistically significant reduction in the number of culture-positive samples was observed for the PLEX-doxycycline-coated group when compared to the animals that had received an uncoated nail, although the reduction in bacterial burden did not reach statistical significance. In conclusion, the PLEX-doxycycline coating on titanium alloy implants provided complete protection against implant-associated MSSA osteomyelitis, and resulted in a significant reduction in the number of culture positive samples when challenged with a

  5. Effect of cathodic polarization on coating doxycycline on titanium surfaces.

    Science.gov (United States)

    Geißler, Sebastian; Tiainen, Hanna; Haugen, Håvard J

    2016-06-01

    Cathodic polarization has been reported to enhance the ability of titanium based implant materials to interact with biomolecules by forming titanium hydride at the outermost surface layer. Although this hydride layer has recently been suggested to allow the immobilization of the broad spectrum antibiotic doxycycline on titanium surfaces, the involvement of hydride in binding the biomolecule onto titanium remains poorly understood. To gain better understanding of the influence this immobilization process has on titanium surfaces, mirror-polished commercially pure titanium surfaces were cathodically polarized in the presence of doxycycline and the modified surfaces were thoroughly characterized using atomic force microscopy, electron microscopy, secondary ion mass spectrometry, and angle-resolved X-ray spectroscopy. We demonstrated that no hydride was created during the polarization process. Doxycycline was found to be attached to an oxide layer that was modified during the electrochemical process. A bacterial assay using bioluminescent Staphylococcus epidermidis Xen43 showed the ability of the coating to reduce bacterial colonization and planktonic bacterial growth. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. The effect of AVE 0991, nebivolol and doxycycline on inflammatory mediators in an apoE-knockout mouse model of atherosclerosis.

    Science.gov (United States)

    Jawien, Jacek; Toton-Zuranska, Justyna; Kus, Katarzyna; Pawlowska, Malgorzata; Olszanecki, Rafal; Korbut, Ryszard

    2012-10-01

    The aim of this study was to investigate whether the 3 different substances that can decrease the development of atherosclerosis--nebivolol, AVE 0991 and doxycycline--could at the same time diminish the level of inflammatory indicators interleukin-6 (IL-6), interleukin-12 (IL-12), serum amyloid A (SAA), and monocyte chemotactic protein-1 (MCP-1). Forty 8-week-old female apoE-knockout mice on the C57BL/6J background were divided into 4 groups and put on chow diet for 4 months. Three experimental groups received the same diet as a control group, mixed with AVE 0991 at a dose 0.58 µmol per kg of body weight per day, nebivolol at a dose 2.0 µmol per kg of body weight per day, and doxycycline at a dose 1.5 mg per kg of body weight per day. At the age of 6 months, the mice were sacrificed. All inflammatory indicators (MCP-1, IL-6, IL-12 and SAA) were diminished by AVE 0991. There was also a tendency to lower MCP-1, IL-6, IL-12 and SAA levels by nebivolol and doxycycline; however, it did not reach statistical significance. Of the 3 presented substances, only AVE 0991 was able to diminish the rise of inflammatory markers. Therefore, drug manipulations in the renin-angiotensin-aldosterone axis seem to be the most promising in the future treatment of atherogenesis.

  7. A combination treatment of folic acid, aspirin, doxycycline and progesterone for women with recurrent early pregnancy loss; hospital based study

    Directory of Open Access Journals (Sweden)

    Kamal M. Zahran

    2016-03-01

    Full Text Available Objective: The study aims to state the effectiveness of a new combination treatment composed of folic acid, doxycycline, low dose aspirin and natural progesterone in cases of recurrent early pregnancy loss. Study design: A clinical comparative hospital-based study. Setting: Women Health Hospital – Assiut University – Egypt. Materials and methods: All patients with recurrent early pregnancy loss at 10 weeks or less attending our antenatal care unit were included. The patients were recruited over a period of 16 months and allocated into two groups. The study group received a regimen of folic acid, doxycycline, aspirin, and progesterone. The control group did not receive the previous regimen in the proposed way. The main outcome measures the live birth rate and complications of pregnancy in both groups. Results: Three hundred patients were recruited, with 150 women in each group. A high rate of live births was found in the study group (76.0% more than the control group (59.3%. Women in the Control Group reported more complications (76.0% vs. 51.3%. These were mainly abortion (40.0% vs. 23.3%, pre-eclampsia (16.0% vs. 10.7% and oligohydramnios (10.0% vs. 6.7%. Conclusion: The implementation of combination treatment of folic acid, doxycycline, low dose aspirin and natural progesterone resulted in a significant increase in the live birth rate, a significant reduction in miscarriages, and lower incidence of complications in patients with recurrent early pregnancy loss.

  8. Doxycycline for Malaria Chemoprophylaxis and Treatment: Report from the CDC Expert Meeting on Malaria Chemoprophylaxis

    Science.gov (United States)

    Tan, Kathrine R.; Magill, Alan J.; Parise, Monica E.; Arguin, Paul M.

    2011-01-01

    Doxycycline, a synthetically derived tetracycline, is a partially efficacious causal prophylactic (liver stage of Plasmodium) drug and a slow acting blood schizontocidal agent highly effective for the prevention of malaria. When used in conjunction with a fast acting schizontocidal agent, it is also highly effective for malaria treatment. Doxycycline is especially useful as a prophylaxis in areas with chloroquine and multidrug-resistant Plasmodium falciparum malaria. Although not recommended for pregnant women and children doxycycline. This report examines the evidence behind current recommendations for the use of doxycycline for malaria and summarizes the available literature on its safety and tolerability. PMID:21460003

  9. What happens when we routinely give doxycycline to medical abortion patients?

    Science.gov (United States)

    Frye, Laura J; Chong, Erica; Winikoff, Beverly

    2015-01-01

    Routine provision of antibiotics following medical abortion is common yet practitioners and professional societies differ on its utility. Our study compares the side effects experienced by women who were prescribed doxycycline following medical abortion to those who were not and assesses the adherence to one prescribed regimen. This was a prospective, observational, open-label study from a convenience sample. Women seeking medical abortion were enrolled in nine study sites, including four clinics that routinely prescribe a seven-day course of doxycycline (Doxycycline arm) and five clinics that do not routinely prescribe any antibiotics (No Doxycycline arm). Seven to fourteen days following the administration of mifepristone, women were asked to self-administer a computer-based survey. The survey asked about side effects experienced (both arms) and adherence to the regimen (Doxycycline arm only). Five hundred eighty-one women were enrolled (278 in the Doxycycline arm and 303 in the No Doxycycline arm). There was a trend toward increased nausea in the Doxycycline arm (47.8% vs. 40.9%; p=.056) and a statistically significant difference in vomiting (25.2% vs. 18.5%; p=.032). Almost all women in the Doxycycline arm reported taking at least one pill, however only 28.3% reported "perfect adherence." The most common reasons reported for taking fewer pills than instructed were that participants were still taking them (beyond 7 days) or that they forgot to take them. Women who were prescribed doxycycline following medical abortion reported moderate adherence and experienced significantly more vomiting than their counterparts. In the absence of robust evidence that prescribing 7 days of doxycycline following medical abortion is effective at reducing serious infections, these data can assist the public health community with deciding whether routine provision is the most appropriate strategy. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase

    Science.gov (United States)

    WANG, CHUNHUAI; XIANG, RU; ZHANG, XIANGZHONG; CHEN, YUNXIAN

    2015-01-01

    Doxycycline, a tetracycline-based antibiotic, has been reported to attenuate melanoma cell migration through inhibiting the focal adhesion kinase (FAK) signaling pathway. However, it remains to be elucidated whether doxycycline exerts this effect on leukemia cell migration. The present study aimed to examine the role of doxycycline in leukemia cell migration. The invasion capacities of the human leukemia cell lines KG1a (acute myelogenous leukemia) and K562 (chronic myelogenous leukemia) were evaluated using Matrigel® matrix-coated Transwell® chamber assays; leukemic cell lines treated with doxycycline (1 µg/ml) or anti-β1-integrin antibodies were added to the upper chamber, while untreated cells were included as controls. Reverse transcription quantitative polymerase chain reaction was performed in order to further understand the influence of doxycycline treatment on the expression of FAK and gelatinases in the KG1a and K562 leukemic cell lines. In addition, FAK protein expression and phosphorylation were determined using western blot analysis in order to investigate the mechanism by which doxycycline inhibited leukemic cell migration. The results revealed that doxycycline treatment significantly attenuated the migration of KG1a and K562 cells, which was demonstrated to be associated with inhibition of the expression and phosphorylation of FAK. In addition, doxycycline treatment inhibited matrix metalloproteinase (MMP)-2 and MMP-9 expression. Furthermore, incubation with blocking anti-β1-integrin antibodies had an analogous inhibitory effect on leukemic cell migration to that of doxycycline. In conclusion, the results of the present study suggested that doxycycline attenuated leukemic cell migration through inhibiting the FAK signaling pathway. Therefore, doxycycline may have potential for use as a novel strategy for the treatment of leukemia. PMID:26004127

  11. The effects of doxycycline on reducing symptoms in knee osteoarthritis: results from a triple-blinded randomised controlled trial

    NARCIS (Netherlands)

    Snijders, G.F.; Ende, C.H.M. van den; Riel, P.L. van; Hoogen, F.H. Van den; Broeder, A. den

    2011-01-01

    OBJECTIVES: Evidence suggests that doxycycline might have disease-modifying properties in osteoarthritis. However, the clinically relevant question as to whether doxycycline also modifies symptoms in knee osteoarthritis is unanswered. The objective of this study was to investigate the effectiveness

  12. Randomized double-blind evaluation of ciprofloxacin and doxycycline for Mediterranean spotted fever.

    OpenAIRE

    Gudiol, F; Pallares, R; Carratala, J; Bolao, F; Ariza, J; Rufi, G; Viladrich, P F

    1989-01-01

    A study of 43 patients with Mediterranean spotted fever showed that a 2-day course of ciprofloxacin or a 2-day course of doxycycline may be an effective mode of therapy. All patients in both arms of the study were cured; however, doxycycline produced a more rapid defervescence.

  13. Doxycycline assay hair samples for testing long-term compliance treatment.

    Science.gov (United States)

    Angelakis, Emmanouil; Armstrong, Nicholas; Nappez, Claude; Richez, Magalie; Chabriere, Eric; Raoult, Didier

    2015-11-01

    Many patients undergoing long-term doxycycline treatment do not regularly take their treatment because of photosensitivity. Our objective was to create an assay for determining doxycycline levels and to use hair samples for monitoring the compliance over a longer period of time. We tested sera and hair samples from patients treated with doxycycline by a suitable ultra-high performance liquid chromatography (UHPLC) based assay. We estimated that the speed of hair growth is roughly 1.25 cm per month and we were able to determine doxycycline levels over a 6-month period. We tested 14 patients treated with doxycycline and we found similar levels of doxycycline in the serum and the hair samples representing the last 4 months. Linear regression analysis revealed that the level of doxycycline in the serum remained stable over time (p = 0.7) but the level of doxycycline in the hair decreased significantly over time (p = 0.03) indicating a degradation of this molecule in the hair. We detected two patients who did not have antibiotic in the hair, indicating a lack of compliance that was also confirmed by interview. Hair samples can be used to test long-term compliance in patients to explain failures or relapses. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  14. Inhibition of MMP synthesis by doxycycline and chemically modified tetracyclines (CMTs) in human endothelial cells

    NARCIS (Netherlands)

    Hanemaaijer, R.; Visser, H.; Koolwijk, P.; Sorsa, T.; Salo, T.; Golub, L.M.; Hinsbergh, V.W. van

    1998-01-01

    Doxycycline is a commonly used broad-spectrum antibiotic. Recently, it has been shown that it also inhibits the activity of mammalian collagenases and gelatinases, an activity unrelated to its antimicrobial efficacy. In this study, we show that doxycycline not only inhibits MMP-8 and MMP-9

  15. Revisiting doxycycline in pregnancy and early childhood – time to rebuild its reputation?

    Science.gov (United States)

    Cross, Ruby; Ling, Clare; Day, Nicholas P. J.; McGready, Rose; Paris, Daniel H.

    2016-01-01

    ABSTRACT Introduction: Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its classification alongside the tetracyclines – class D drugs, contraindicated in pregnancy and in children under 8 years of age. Doxycycline-treatable diseases are emerging as leading causes of undifferentiated febrile illness in Southeast Asia. For example scrub typhus and murine typhus have an unusually severe impact on pregnancy outcomes, and current mortality rates for scrub typhus reach 12-13% in India and Thailand. The emerging evidence for these important doxycycline-treatable diseases prompted us to revisit doxycycline usage in pregnancy and childhood. Areas Covered: A systematic review of the available literature on doxycycline use in pregnant women and children revealed a safety profile of doxycycline that differed significantly from that of tetracycline; no correlation between the use of doxycycline and teratogenic effects during pregnancy or dental staining in children was found. Expert Opinion: The change of the US FDA pregnancy classification scheme to an evidence-based approach will enable adequate evaluation of doxycycline in common tropical illnesses and in vulnerable populations in clinical treatment trials, dosage-optimization pharmacokinetic studies and for the empirical treatment of undifferentiated febrile illnesses, especially in pregnant women and children. PMID:26680308

  16. Revisiting doxycycline in pregnancy and early childhood--time to rebuild its reputation?

    Science.gov (United States)

    Cross, Ruby; Ling, Clare; Day, Nicholas P J; McGready, Rose; Paris, Daniel H

    2016-01-01

    Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its classification alongside the tetracyclines - class D drugs, contraindicated in pregnancy and in children under 8 years of age. Doxycycline-treatable diseases are emerging as leading causes of undifferentiated febrile illness in Southeast Asia. For example scrub typhus and murine typhus have an unusually severe impact on pregnancy outcomes, and current mortality rates for scrub typhus reach 12-13% in India and Thailand. The emerging evidence for these important doxycycline-treatable diseases prompted us to revisit doxycycline usage in pregnancy and childhood. A systematic review of the available literature on doxycycline use in pregnant women and children revealed a safety profile of doxycycline that differed significantly from that of tetracycline; no correlation between the use of doxycycline and teratogenic effects during pregnancy or dental staining in children was found. The change of the US FDA pregnancy classification scheme to an evidence-based approach will enable adequate evaluation of doxycycline in common tropical illnesses and in vulnerable populations in clinical treatment trials, dosage-optimization pharmacokinetic studies and for the empirical treatment of undifferentiated febrile illnesses, especially in pregnant women and children.

  17. 77 FR 39708 - Renewal of Declaration Regarding Emergency Use of All Oral Formulations of Doxycycline...

    Science.gov (United States)

    2012-07-05

    ... Emergency Use of All Oral Formulations of Doxycycline Accompanied by Emergency Use Information AGENCY... the Federal Food, Drug, and Cosmetic Act (``FD&C Act''), the Secretary of Health and Human Services is... oral formulations of doxycycline accompanied by emergency use information subject to the terms of any...

  18. 77 FR 40060 - Renewal of Declaration Regarding Emergency Use of All Oral Formulations of Doxycycline...

    Science.gov (United States)

    2012-07-06

    ... HUMAN SERVICES Renewal of Declaration Regarding Emergency Use of All Oral Formulations of Doxycycline... determination, and pursuant to section 564(b) of the Federal Food, Drug, and Cosmetic Act (``FD&C Act''), the... the authorization of emergency use of all oral formulations of doxycycline accompanied by emergency...

  19. Doxycycline use in patients with lymphangioleiomyomatosis: biomarkers and pulmonary function response *, **

    Science.gov (United States)

    Pimenta, Suzana Pinheiro; Baldi, Bruno Guedes; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

    2013-01-01

    OBJECTIVE: To assess blockade of matrix metalloproteinase (MMP)-2 and MMP-9, as well as the variation in FEV1, in patients with lymphangioleiomyomatosis (LAM) treated with doxycycline (a known MMP inhibitor) for 12 months. METHODS: An open-label, single-arm, interventional clinical trial in which LAM patients received doxycycline (100 mg/day) for 12 months. Patients underwent full pulmonary function testing, a six-minute walk test, and quality of life assessment, as well as blood and urine sampling for quantification of MMP-2, MMP-9, and VEGF-D levels-at baseline, as well as at 6 and 12 months after the initiation of doxycycline. RESULTS: Thirty-one LAM patients received doxycycline for 12 months. Although there was effective blockade of urinary MMP-9 and serum MMP-2 after treatment, there were no significant differences between pre and post-doxycycline serum levels of MMP-9 and VEGF-D. On the basis of their response to doxycycline (as determined by the variation in FEV1), the patients were divided into two groups: the doxycycline-responder (doxy-R) group (n = 13); and the doxycycline-nonresponder (doxy-NR) group (n = 18). The patients with mild spirometric abnormalities responded better to doxycycline. The most common side effects were mild epigastric pain, nausea, and diarrhea. CONCLUSIONS: In patients with LAM, doxycycline treatment results in effective MMP blockade, as well as in improved lung function and quality of life in those with less severe disease. However, these benefits do not seem to be related to the MMP blockade, raising the hypothesis that there is a different mechanism of action. PMID:23503480

  20. Doxycycline blocks gastric ulcer by regulating matrix metalloproteinase-2 activity and oxidative stress

    Science.gov (United States)

    Singh, Laishram Pradeepkumar; Mishra, Amartya; Saha, Debjit; Swarnakar, Snehasikta

    2011-01-01

    AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury. METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol, and activity of doxycycline was tested by administration 30 min prior to ethanol. Similarly, the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model. The activities and expression of MMPs were examined by zymography and Western blot analysis. RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen, either indomethacin or ethanol, was reversed significantly by doxycycline. Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues. Similarly, ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities, respectively, in rat gastric tissues. Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues. In contrast, the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention. On the other hand, doxycycline inhibited significantly proMMP-9, -2 and -3 activities in vitro. In addition, doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro. Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers. CONCLUSION: This is the first demonstration of dual action of doxycycline, that is, regulation of MMP activity and reduction of oxidative stress in arresting gastric injury. PMID:21876619

  1. New intracanal formulations containing doxycycline or chlorhexidine against Enterococcus faecalis.

    Science.gov (United States)

    Silva, Ana Rita Marques da; Pinto, Shelon Cristina Souza; Santos, Elizabete Brasil dos; Santos, Fábio André dos; Farago, Paulo Vitor; Gomes, João Carlos; Pina-Vaz, Irene; Carvalho, Manuel Fontes

    2014-01-01

    The present study aims to evaluate the antimicrobial effect of two new intracanal preparations against E. faecalis. Thirty single-rooted human canine teeth were used. The crowns were removed and the roots were instrumented using a conventional technique. Three groups of ten teeth each were infected with 108 CFU/ ml of E. faecalis for 21 days. The root canals were flled with new intracanal medications containing 3% doxycycline hydrochloride (DX) or 2% chlorhexidine digluconate (CHX). Ten teeth received no medication (NM)-negative control. Microbial samples were obtained 21 days after contamination: 14 days under the effect of the intracanal medications and 7 days after replacing the medications by BHI broth. The samples were homogenized, diluted, seeded on BHI agar and incubated for 48h/36°C. The number of colony forming units (CFU/ml) was obtained and analyzed statistically. All intracanal dressings significantly reduced the number of bacterial cells in the root canal after 14 days with medication. After the period with 7 days with BHI broth, the CFU counts of E. faecalis remained at low values. However, the NM group showed a significant increase of CFU in this period to similar values of the initial contamination. 3% doxycycline hydrochloride gel and 2% CHX gel were effective to eliminate E. faecalis from the root canal system.

  2. Inhibition of ADAMTS-13 by Doxycycline Reduces von Willebrand Factor Degradation During Supraphysiological Shear Stress: Therapeutic Implications for Left Ventricular Assist Device-Associated Bleeding.

    Science.gov (United States)

    Bartoli, Carlo R; Kang, Jooeun; Restle, David J; Zhang, David M; Shabahang, Cameron; Acker, Michael A; Atluri, Pavan

    2015-11-01

    The aim of this study was to investigate a potential therapy for left ventricular assist device (LVAD)-associated bleeding. Nonsurgical bleeding is the most frequent complication of LVAD support. Recent evidence has demonstrated that supraphysiological shear stress from continuous-flow LVADs accelerates von Willebrand factor (vWF) metabolism by the action of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) (the vWF protease). An acquired vWF deficiency causes bleeding. This suggests that ADAMTS-13 is a clinical target to reduce vWF degradation. We tested the hypothesis that inhibition of ADAMTS-13 with doxycycline, an inexpensive, clinically approved drug, reduces vWF degradation during shear stress. Whole blood was collected from human donors (n = 15), and purified, recombinant ADAMTS-13 protein was obtained. An enzyme-linked immunosorbent assay (ELISA) was used to quantify the dose relationship between doxycycline and ADAMTS-13 activity prior to shear stress (n = 10). To determine the effect of shear stress, plasma and recombinant ADAMTS-13 were exposed to LVAD-like supraphysiological shear stress (approximately 175 dyne/cm(2)). vWF multimers and degradation fragments were characterized with electrophoresis and immunoblotting (n = 10). Förster resonance energy transfer was used to quantify plasma ADAMTS-13 activity (n = 10). An ELISA was used to quantify vWF:collagen binding activity. Platelet aggregometry was performed with adenosine 5'-diphosphate, collagen, and ristocetin (vWF-platelet pathway) agonism (n = 10). Doxycycline significantly decreased plasma ADAMTS-13 activity (p = 0.01) and the activity of recombinant human ADAMTS-13 protein by 21%. After plasma was exposed to shear stress, the same pattern of vWF degradation was observed as previously reported for LVAD patients, and vWF:collagen binding activity decreased significantly (p = 0.002). Doxycycline significantly decreased ADAMTS-13 activity (p = 0.04) and

  3. Application of novel metal organic framework, MIL-53(Fe) and its magnetic hybrid: For removal of pharmaceutical pollutant, doxycycline from aqueous solutions.

    Science.gov (United States)

    Naeimi, Shakiba; Faghihian, Hossein

    2017-07-01

    As a pharmaceutical pollutant, doxycycline causes contamination when enters into the environment. In this research MIL-53(Fe), and its magnetic hybrid MIL-53(Fe)/Fe 3 O 4 were synthesized and employed for removal of doxycycline from aqueous solutions. The adsorbents were characterized by XRD, SEM, BET, FTIR, EDAX, VSM and TG-DTG technique. The effect of different variables such as DOC concentration, pH, contacting time, and adsorbent dose on the removal efficiency was studied and under optimized conditions the adsorption capacity of 322mgg -1 was obtained. The adsorption process was kinetically fast and the equilibration was attained within 30min. The used adsorbent was easily separated from the solution by applying external magnetic field. The regenerated adsorbent retained most of its initial capacity after six regeneration steps. The effect of ionic strength was studied and it was indicated that removal of doxycycline from salt-containing water with moderate ionic strengths was quite feasible. Langmuir, Freundlich, Tempkin and Dubinin-Redushkevich isotherms were employed to describe the nature of adsorption process. The sorption data was well interpreted by the Longmuir model. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Local and Sustained Activity of Doxycycline Delivered with Layer-by-Layer Microcapsules.

    Science.gov (United States)

    Luo, Dong; Gould, David J; Sukhorukov, Gleb B

    2016-04-11

    Achieving localized delivery of small molecule drugs has the potential to increase efficacy and reduce off target and side effects associated with systemic distribution. Herein, we explore the potential use of layer-by-layer (LbL) assembled microcapsules for the delivery of doxycycline. Absorbance of doxycycline onto core dextran sulfate of preassembled microcapsules provides an efficient method to load both synthetic and biodegradable microcapsules with the drug. Application of an outer layer lipid coat enhances the sustained in vitro release of doxycycline from both microcapsule types. To monitor doxycycline delivery in a biological system, C2C12 mouse myoblasts are engineered to express EGFP under the control of the optimized components of the tetracycline regulated gene expression system. Microcapsules are not toxic to these cells, and upon delivery to the cells, EGFP is more efficiently induced in those cells that contain engulfed microcapsules and monitored EGFP expression clearly demonstrates that synthetic microcapsules with a DPPC coat are the most efficient for sustain intracellular delivery. Doxycycline released from microcapsules also displayed sustained activity in an antimicrobial growth inhibition assay compared with doxycycline solution. This study reveals the potential for LbL microcapsules in small molecule drug delivery and their feasible use for achieving prolonged doxycycline activity.

  5. A new therapeutic association to manage relapsing experimental colitis: Doxycycline plus Saccharomyces boulardii.

    Science.gov (United States)

    Garrido-Mesa, José; Algieri, Francesca; Rodriguez-Nogales, Alba; Utrilla, Maria Pilar; Rodriguez-Cabezas, Maria Elena; Zarzuelo, Antonio; Ocete, Maria Angeles; Garrido-Mesa, Natividad; Galvez, Julio

    2015-07-01

    Immunomodulatory antibiotics have been proposed for the treatment of multifactorial conditions such as inflammatory bowel disease. Probiotics are able to attenuate intestinal inflammation, being considered as safe when chronically administered. The aim of the study was to evaluate the anti-inflammatory effects of doxycycline, a tetracycline with immunomodulatory properties, alone and in association with the probiotic Saccharomyces boulardii CNCMI-745. Doxycycline was assayed both in vitro (Caco-2 epithelial cells and RAW 264.7 macrophages) and in vivo, in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis and the dextran sodium sulfate (DSS) model of mouse colitis. In addition, the anti-inflammatory effect of the association of doxycycline and the probiotic was evaluated in vitro and in vivo in a DSS model of reactivated colitis in mice. Doxycycline displayed immunomodulatory activity in vitro, reducing IL-8 production by intestinal epithelial cells and nitric oxide by macrophages. Doxycycline administration to TNBS-colitic rats (5, 10 and 25 mg/kg) ameliorated the intestinal inflammatory process, being its efficacy comparable to that previously showed by minocycline. Doxycycline treatment was also effective in reducing acute intestinal inflammation in the DSS model of mouse colitis. The association of doxycycline and S. boulardii helped managing colitis in a reactivated model of colitis, by reducing intestinal inflammation and accelerating the recovery and attenuating the relapse. This was evidenced by a reduced disease activity index, colonic tissue damage and expression of inflammatory mediators. This study confirms the intestinal anti-inflammatory activity of doxycycline and supports the potential use of its therapeutic association with S. boulardii for the treatment of inflammatory bowel diseases, in which doxycycline is used to induce remission and long term probiotic administration helps to prevent the relapses. Copyright © 2015 Elsevier Ltd. All

  6. Effects of Doxycycline on Mesenchymal Stem Cell Chondrogenesis and Cartilage Repair

    Science.gov (United States)

    Friel, Nicole A.; Chu, Constance R.

    2017-01-01

    Objective Strategies to improve cartilage repair tissue quality after bone marrow cell-based procedures may reduce later development of osteoarthritis. Doxycycline is inexpensive, well-tolerated, and has been shown to reduce matrix-metalloproteinases (MMP) and osteoarthritis progression. This study tests the hypotheses that doxycycline reduces MMP, enhances chondrogenesis of human bone marrow-derived mesenchymal stem cells (hMSC), and improves in vivo cartilage repair. Design Ninety hMSC pellets were cultured in chondrogenic media with either 0-, 1- or 2-μg/mL doxycycline. Pellets were evaluated with stereomicroscopy, proteoglycan assay, qRT-PCR, and histology. Osteochondral defects (OCD) were created in the trochlear grooves of 24-Sprague-Dawley rats treated with/without oral doxycycline. Rats were sacrificed at 12-weeks and repair tissues were examined grossly and histologically. Results hMSC pellets with 1-μg/mL (p=0.014) and 2-μg/mL (p=0.002) doxycycline had larger areas than pellets without doxycycline. hMSC pellets with 2-μg/mL doxycycline showed reduced mmp-13 mRNA (p=0.010) and protein at 21-days. Proteoglycan, DNA contents, and mRNA expressions of chondrogenic genes were similar (p>0.05). For the in vivo study, while the histological scores were similar between the two groups (p=0.116), the gross scores of the OCD repair tissues in doxycycline-treated rats were higher at 12-weeks (p=0.017), reflective of improved repair quality. The doxycycline-treated repairs also showed lower MMP-13 protein (p=0.029). Conclusions This study shows that doxycycline improves hMSC chondrogenesis and decreases MMP-13 in pellet cultures and within rat OCDs. Doxycycline exerted no negative effect on multiple measures of chondrogenesis and cartilage repair. These data support potential use of doxycycline to improve cartilage repair to delay the onset of osteoarthritis. PMID:23186943

  7. Doxycycline Enhances Survival and Self-Renewal of Human Pluripotent Stem Cells

    Science.gov (United States)

    Chang, Mi-Yoon; Rhee, Yong-Hee; Yi, Sang-Hoon; Lee, Su-Jae; Kim, Rae-Kwon; Kim, Hyongbum; Park, Chang-Hwan; Lee, Sang-Hun

    2014-01-01

    Summary We here report that doxycycline, an antibacterial agent, exerts dramatic effects on human embryonic stem and induced pluripotent stem cells (hESC/iPSCs) survival and self-renewal. The survival-promoting effect was also manifest in cultures of neural stem cells (NSCs) derived from hESC/iPSCs. These doxycycline effects are not associated with its antibacterial action, but mediated by direct activation of a PI3K-AKT intracellular signal. These findings indicate doxycycline as a useful supplement for stem cell cultures, facilitating their growth and maintenance. PMID:25254347

  8. Malaria Chemoprophylaxis and Self-Reported Impact on Ability to Work: Mefloquine Versus Doxycycline.

    Science.gov (United States)

    Terrell, Andrew G; Forde, Mike E; Firth, Richard; Ross, David A

    2015-01-01

    It is well known that both mefloquine and doxycycline are commonly associated with adverse effects when taken for malaria chemoprophylaxis. However, the relative impact of these on travelers' ability to work is not so well understood. The aim of this study was to identify which drug has a lesser impact on the ability to work as measured by self-reported severity of adverse effects via a questionnaire. This was a questionnaire-based two-arm cohort study. Participants were soldiers selected from 10 consecutive units training in Kenya during 2012 and 2013. The exposure was either doxycycline or mefloquine and the main outcome measure was impact upon ability to work. Each cohort was advised to take doxycycline or mefloquine with exceptions at the individual level where medically or occupationally advised. Significantly more (p doxycycline users reported that one or more adverse effects had interfered with their ability to do their job than mefloquine users. Of the 867 mefloquine users, who reported on the impact of adverse effects, 109 (12.6%) reported that one or more adverse effects had impacted upon their ability to do their job, compared to 152 (22.2%) of the 685 doxycycline users who had reported on the impact of any adverse effects. Doxycycline symptoms were predominantly gastrointestinal and dermatological, whereas mefloquine symptoms were neuropsychiatric. Self-reported symptoms were common in those that responded and, while the true background rate of adverse effects (off any medication) is unknown, doxycycline had a significantly increased rate compared with mefloquine and was associated with a greater occupational impact. Therefore, this study supports the view that, for organizations which provide malaria chemoprophylaxis to employees free of charge, mefloquine should be the first-choice antimalarial drug where the only alternative is doxycycline. © 2015 Crown copyright. Journal of Travel Medicine © 2015 International Society of Travel Medicine.

  9. Doxycycline Inhibits Inflammation-Induced Lymphangiogenesis in Mouse Cornea by Multiple Mechanisms

    Science.gov (United States)

    Huang, Jingwen; Zhou, Jingwen; Qiu, Sujuan; Liang, Dan

    2014-01-01

    Lymphangiogenesis is significantly involved in the pathogenesis of diseases, including graft rejection, cancer metastasis and various inflammatory conditions. The inhibition of lymphangiogenesis has become a new therapeutic target for the treatment of these diseases. Here, we explored the anti-lymphangiogenic effects of doxycycline in inflammation-induced lymphangiogenesis (ILA) in the cornea and the underlying mechanisms. In the present study, mice with ILA of the cornea were treated with topical doxycycline (0.1%) or vehicle control. Lymphangiogenesis was quantified using corneal immunostaining of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1). Human dermal lymphatic endothelial cells (HDLECs) and a murine macrophage cell line (RAW264.7) were used to further explore the underlying mechanisms of doxycycline-mediated anti-lymphangiogenesis in vitro. Our results showed that doxycycline treatment dramatically inhibited ILA in the mouse cornea (pDoxycycline also significantly inhibited VEGF-C-induced HDLEC proliferation in vitro by modulating the PI3K/Akt/endothelial nitric oxide (NO) synthase (eNOS) pathway and significantly suppressed interleukin-1β (IL-1β), TNF-α and VEGF-C production in the RAW264.7 cell line by modulating the PI3K/Akt/nuclear factor-kappaB (NF-κB) pathway. Additionally, doxycycline treatment dramatically reduced the phosphorylation of NF-κBp65, Akt and eNOS in ILA and significantly inhibited matrix metalloproteinases (MMPs) activity in vitro and in ILA. In conclusion, doxycycline inhibited ILA, possibly through suppression of VEGF-C signalling, macrophage function and MMPs activity. This observation suggests that doxycycline is a potential therapeutic agent for lymphangiogenesis-related diseases. PMID:25268699

  10. Effects of doxycycline on local and systemic inflammation in stable COPD patients, a randomized clinical trial.

    Science.gov (United States)

    Prins, Hendrik J; Daniels, Johannes M A; Lindeman, Jan H; Lutter, René; Boersma, Wim G

    2016-01-01

    Neutrophilic inflammation plays a causal role in Chronic Obstructive Pulmonary Disease (COPD). Neutrophil derived myeloperoxidase(MPO) matrix metalloproteinases(MMP's), and elastases are thought to contribute to the perpetuation of the disease. The tetracycline analogue doxycycline has been shown to inhibit neutrophil-mediated inflammation. It was thus reasoned that doxycycline may attenuate neutrophil-mediated inflammation in COPD. In this double blind randomized controlled trial the effect of a 3-week course of doxycycline on sputum and systemic inflammatory parameters was evaluated in stable COPD patients. In order to exclude inflammation by bacterial colonisation patients must have 2 negative sputum cultures in the previous year. The effect of doxycycline treatment on inflammatory markers (TNF-α, IL-1β and IL-6) and neutrophil specific markers in sputum (MPO, MMP's, and IL-8) and serum C-reactive protein was evaluated. Sputum was obtained by sputum induction with hypertonic saline. A total of 41 patients were included. Ten patients were excluded as they were not able to produce sputum at the first or second visit. Baseline characteristics were similar in the two groups. In the remaining patients doxycycline did not influence sputum MPO concentrations. Also MMP-8 and 9, IL-6 and IL-8 concentrations as well as lung function parameters were not affected by doxycycline. Systemic inflammation by means of CRP was also not influenced by doxycycline. A three week course of doxycycline did not influence MPO sputum levels nor any of the other inflammatory sputum and systemic markers. ClinicalTrials.gov; No.: NCT00857038 URL: clinicaltrials.gov. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Effect of doxycycline on stifle lameness: a preliminary clinical observation in twelve dogs

    Directory of Open Access Journals (Sweden)

    Kei Hayashi

    2011-07-01

    Full Text Available The clinical efficacy of oral doxycycline was evaluated in twelve dogs with stifle arthritis and a presumptive diagnosis of early cruciate disease. Doxycycline (2.5-4.5 mg/kg once daily was administered orally for 3 to 8 weeks. Eight dogs, who presented prior to the treatment with clinical signs of 4 weeks or fewer duration (group B, had a good response to doxycycline, whereas four dogs with a longer history of lameness (group A had a poor response. The follow-up periods ranged from 2 to 12 months after discontinuation of the doxycycline treatment (median=6.5 months, 3 months in group A, and 9.5 months in group B. There was a significant correlation between the duration of lameness and the subjective grading of clinical improvement. In 68% of these cases of dogs with stifle arthritis (8/12, the oral administration of doxycycline resulted in the improvement of lameness, even after discontinuation of doxycycline. Careful selection of patients based on the duration of their lameness appears to be crucial in order to achieve a positive outcome.

  12. Testing the Therapeutic Potential of Doxycycline in a Drosophila melanogaster Model of Alzheimer Disease*

    Science.gov (United States)

    Costa, Rita; Speretta, Elena; Crowther, Damian C.; Cardoso, Isabel

    2011-01-01

    Therapies for Alzheimer disease that reduce the production of pathogenic amyloid β (Aβ) peptides have been associated with a range of unwanted effects. For this reason, alternative strategies that promote the clearance of the peptide by preventing its aggregation and deposition in the brain have been favored. In this context we have studied doxycycline, a member of the tetracycline family of antibiotics that has shown neuroprotective effects in a number of models of neurodegenerative disease. We investigated the neuroprotective potential of doxycycline in a Drosophila model of Aβ toxicity and sought to correlate any effects with the aggregation state of the peptide. We found that administration of doxycycline to Aβ42-expressing flies did not improve their lifespan but was able to slow the progression of their locomotor deficits. We also measured the rough eye phenotype of transgenic flies expressing the E22G variant of Aβ42 and showed that doxycycline administration partially rescued the toxicity of Aβ in the developing eye. We correlated these in vivo effects with in vitro observations using transmission electron microscopy, dynamic light scattering, and thioflavin T binding. We found that doxycycline prevents Aβ fibrillization and favors the generation of smaller, non-amyloid structures that were non-toxic as determined by the lack of caspase 3 activation in a neuroblastoma cell line. Our confirmation that doxycycline can prevent amyloid β toxicity both in vitro and in vivo supports its therapeutic potential in AD. PMID:21998304

  13. The end of a dogma: the safety of doxycycline use in young children for malaria treatment.

    Science.gov (United States)

    Gaillard, Tiphaine; Briolant, Sébastien; Madamet, Marylin; Pradines, Bruno

    2017-04-13

    Anti-malarial drug resistance to chloroquine and sulfadoxine-pyrimethamine has spread from Southeast Asia to Africa. Furthermore, the recent emergence of resistance to artemisinin-based combination therapy (ACT) in Southeast Asia highlights the need to identify new anti-malarial drugs. Doxycycline is recommended for malaria chemoprophylaxis for travel in endemic areas, or in combination with the use of quinine for malaria treatment when ACT is unavailable or when the treatment of severe malaria with artesunate fails. However, doxycycline is not used in young children under 8 years of age due to its contraindication due to the risk of yellow tooth discolouration and dental enamel hypoplasia. Doxycycline was developed after tetracycline and was labelled with the same side-effects as the earlier tetracyclines. However, recent studies report little or no effects of doxycycline on tooth staining or dental enamel hypoplasia in children under 8 years of age. In the United States, the Centers for Disease Control and Prevention have recommended the use of doxycycline for the treatment of acute and chronic Q fever and tick-borne rickettsial diseases in young children. It is time to rehabilitate doxycycline and to recommend it for malaria treatment in children under 8 years of age.

  14. Doxycycline inhibits the cancer stem cell phenotype and epithelial-to-mesenchymal transition in breast cancer.

    Science.gov (United States)

    Zhang, Le; Xu, Liang; Zhang, Fengchun; Vlashi, Erina

    2017-04-18

    Experimental evidence suggest that breast tumors originate from breast cancer stem cells (BCSCs), and that mitochondrial biogenesis is essential for the anchorage-independent clonal expansion and survival of CSCs, thus rendering mitochondria a significant target for novel treatment approaches. One of the recognized side effects of the FDA-approved drug, doxycycline is the inhibition of mitochondrial biogenesis. Here we investigate the mechanism by which doxycycline exerts its inhibitory effects on the properties of breast cancer cells and BCSCs, such as mammosphere forming efficiency, invasion, migration, apoptosis, the expression of stem cell markers and epithelial-to-mesenchymal transition (EMT) related markers of breast cancer cells. In addition, we explored whether autophagy plays a role in the inhibitory effect of doxycycline on breast cancer cells. We find that doxycyline can inhibit the viability and proliferation of breast cancer cells and BCSCs, decrease mammosphere forming efficiency, migration and invasion, and EMT of breast cancer cells. Expression of stem cell factors Oct4, Sox2, Nanog and CD44 were also significantly downregulated after doxycycline treatment. Moreover, doxycycline could down-regulate the expression of the autophagy marker LC-3BI and LC-3BII, suggesting that inhibiting autophagy may be responsible in part for the observed effects on proliferation, EMT and stem cell markers. The potent inhibition of EMT and cancer stem-like characteristics in breast cancer cells by doxycycline treatment suggests that this drug can be repurposed as an anti-cancer drug in the treatment of breast cancer patients in the clinic.

  15. DOXYCYCLINE HYDROGELS WITH REVERSIBLE DISULFIDE CROSSLINKS FOR DERMAL WOUND HEALING OF MUSTARD INJURIES

    Science.gov (United States)

    Anumolu, SivaNaga S; Menjoge, Anupa R.; Deshmukh, Manjeet; Gerecke, Donald; Stein, Stanley; Laskin, Jeffrey; Sinko, Patrick J.

    2010-01-01

    Doxycycline hydrogels containing reversible disulfide crosslinks were investigated for a dermal wound healing application. Nitrogen mustard (NM) was used as a surrogate to mimic the vesicant effects of the chemical warfare agent sulfur mustard. An 8-arm-poly(ethylene glycol) (PEG) polymer containing multiple thiol (-SH) groups was crosslinked using hydrogen peroxide (H2O2 hydrogel) or 8-arm-S-thiopyridyl (S-TP hydrogel) to form a hydrogel in situ. Formulation additives (glycerin, PVP and PEG 600) were found to promote dermal hydrogel retention for up to 24 h. Hydrogels demonstrated high mechanical strength and a low degree of swelling (Doxycycline release from the hydrogels was biphasic and sustained for up to 10-days in vitro. Doxycycline (8.5 mg/cm3) permeability through NM-exposed skin was elevated as compared to non vesicant-treated controls at 24, 72 and 168 h post exposure with peak permeability at 72 h. The decrease in doxycycline permeability at 168 h correlates to epidermal reepithelialization and wound healing. Histology studies of skin showed that doxycycline-loaded (0.25% w/v) hydrogels provided improved wound healing response on NM-exposed skin as compared to untreated skin and skin treated with placebo hydrogels in a SKH-1 mouse model. In conclusion, PEG-based doxycycline hydrogels are promising for dermal wound healing application of mustard injuries. PMID:20950853

  16. Cooperation of Doxycycline with Phytochemicals and Micronutrients Against Active and Persistent Forms of Borrelia sp.

    Science.gov (United States)

    Goc, Anna; Niedzwiecki, Alexandra; Rath, Matthias

    2016-01-01

    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.

  17. No visible dental staining in children treated with doxycycline for suspected Rocky Mountain Spotted Fever.

    Science.gov (United States)

    Todd, Suzanne R; Dahlgren, F Scott; Traeger, Marc S; Beltrán-Aguilar, Eugenio D; Marianos, Donald W; Hamilton, Charlene; McQuiston, Jennifer H; Regan, Joanna J

    2015-05-01

    To evaluate whether cosmetically relevant dental effects occurred among children who had received doxycycline for treatment of suspected Rocky Mountain spotted fever (RMSF). Children who lived on an American Indian reservation with high incidence of RMSF were classified as exposed or unexposed to doxycycline, based on medical and pharmacy record abstraction. Licensed, trained dentists examined each child's teeth and evaluated visible staining patterns and enamel hypoplasia. Objective tooth color was evaluated with a spectrophotometer. Fifty-eight children who received an average of 1.8 courses of doxycycline before 8 years of age and who now had exposed permanent teeth erupted were compared with 213 children who had never received doxycycline. No tetracycline-like staining was observed in any of the exposed children's teeth (0/58, 95% CI 0%-5%), and no significant difference in tooth shade (P=.20) or hypoplasia (P=1.0) was found between the 2 groups. This study failed to demonstrate dental staining, enamel hypoplasia, or tooth color differences among children who received short-term courses of doxycycline at <8 years of age. Healthcare provider confidence in use of doxycycline for suspected RMSF in children may be improved by modifying the drug's label. Published by Elsevier Inc.

  18. Spectrofluorimetric determination of heparin using doxycycline-europium probe

    Energy Technology Data Exchange (ETDEWEB)

    Li Jing [Department of Chemistry, Shandong Normal University, Jinan 250014 (China); Liu Jinkai [Department of Chemistry, Shandong Normal University, Jinan 250014 (China); Zhu Xiaojing [Department of Chemistry, Shandong Normal University, Jinan 250014 (China); Peng Qian [Department of Chemistry, Shandong Normal University, Jinan 250014 (China); Jiang Chongqiu [Department of Chemistry, Shandong Normal University, Jinan 250014 (China)]. E-mail: jiangchongqiu@sdnu.edu.cn

    2005-06-15

    A new spectrofluorimetric method was developed for the determination of the trace amount of heparin (Hep). Using doxycycline (DC)-europium ion (Eu{sup 3+}) as a fluorescent probe, in the buffer solution of pH=8.9, Hep can remarkably enhance the fluorescence intensity of the DC-Eu{sup 3+} complex at {lambda}=612 nm and the enhanced fluorescence intensity of Eu{sup 3+} ion is in proportion to the concentration of Hep. Optimum conditions for the determination of Hep were also investigated. The linear range and detection limit for the determination of Hep are 0.04-0.8 {mu}g/mL and 19.7 ng/mL, respectively. This method is simple, practical, and relatively free of interference from coexisting substances and can be successfully applied to assess Hep in biological samples. By the Rosenthal graphic method, the association constant and binding numbers of Hep with the probe are 6.60x10{sup 4} L/mol and 33.9. Moreover, the enhancement mechanism of the fluorescence intensity in the DC-Eu{sup 3+} system and the DC-Eu{sup 3+}-Hep-CTMAB system have been also discussed.

  19. Potent Synergistic Effect of Doxycycline with Fluconazole against Candida albicans Is Mediated by Interference with Iron Homeostasis

    Science.gov (United States)

    2012-01-01

    Doxycycline was found to act synergistically with the antifungal fluconazole against Candida albicans. Combination with doxycycline converts fluconazole from fungistatic to fungicidal, prevents the onset of drug resistance, and is also effective against a clinical isolate characterized by elevated resistance to fluconazole. Investigation of the interactions between the two drugs by way of checkerboard assays indicated that doxycycline had an influence on the MIC for fluconazole, as defined by CLSI standards, only at high concentrations (200 μg/ml). However, lower concentrations were effective at eliminating residual cell growth at supra-MICs of fluconazole. Using MIC-0, defined as a drug combination resulting in optically clear wells, as an endpoint, doxycycline was found to be synergistic with fluconazole at a concentration as low as 25 μg/ml, with a fractional inhibitory concentration index of Doxycycline-mediated growth inhibition can be reversed by externally added iron, indicating that iron depletion may account for the synergism. Consistently, we confirmed old literature data about iron-chelating activity of doxycycline. Synergism of fluconazole with doxycycline does not appear to be mediated by calcineurin, since doxycycline further aggravates the susceptibility to fluconazole of mutants lacking the catalytic or the regulatory subunits of calcineurin. Growth in the presence of fluconazole and doxycycline is restored by an elevated dosage of ERG11 in Saccharomyces cerevisiae but not in C. albicans, despite the full competence of the pathogen's protein to act as a suppressor in baker's yeast. PMID:22564841

  20. Doxycycline Sclerotherapy Is Superior in the Treatment of Pediatric Lymphatic Malformations.

    Science.gov (United States)

    Thomas, Debi M; Wieck, Minna M; Grant, Christa N; Dossa, Avafia; Nowicki, Donna; Stanley, Phillip; Zeinati, Chadi; Howell, Lori K; Anselmo, Dean M

    2016-12-01

    To evaluate efficacy of sclerotherapy with doxycycline versus sodium tetradecyl sulfate (STS) for treatment of macrocystic and mixed lymphatic malformations (LMs). This single-center retrospective review identified 41 children (17 boys; 24 girls; age range, 1 month to 15.4 y) who underwent sclerotherapy with doxycycline (n = 32) or STS (n = 9) for macrocystic (n = 31) or mixed (n = 10) LMs. There were 114 treatments performed, averaging 2.8 treatments (range, 1-8 treatments) per patient. Average follow-up time was 10 months (range, 1-59 months). Clinical response was deemed excellent or moderate if > 90% or > 50% of LMs resolved based on visual estimate. With doxycycline, 87% of patients (28 of 32) had excellent or moderate response with an average of 2.8 treatments (range, 1-7 treatments); 13% required subsequent resection. With 3% STS monotherapy, only 55% of patients (5 of 9) had excellent or moderate response with an average of 2.8 treatments (range, 1-8 treatments), and 33% required subsequent resection. Significantly fewer patients treated with STS responded well compared with patients treated with doxycycline (P = .03). Patients treated with STS had significantly longer follow-up than patients treated with doxycycline (27 months vs 6 months, P = .0001). Doxycycline monotherapy resulted in a high rate of excellent clinical outcomes after a few treatments without increased need for subsequent operative resection. These results support use of doxycycline sclerotherapy as primary treatment for macrocystic and mixed LMs in children. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  1. A randomized, comparative study of dual therapy (doxycycline-rifampin) versus triple therapy (doxycycline-rifampin-levofloxacin) for treating acute/subacute brucellosis.

    Science.gov (United States)

    Hasanain, Ahmad; Mahdy, Reem; Mohamed, Asmaa; Ali, Mostafa

    2016-01-01

    The aim of this study was to compare both the efficacy and safety profile of the WHO-recommended, dual therapy (doxycycline-rifampin) to a quinolone-based, triple therapy (doxycycline-rifampin-levofloxacin) for treating acute/subacute brucellosis. We studied 107 consecutive, naïve patients with acute/subacute brucellosis admitted to Assiut University Hospital. Patients were randomly allocated to receive the dual therapy of doxycycline-rifampin (group-A) or to receive the triple therapy of doxycycline-rifampin-levofloxacin (group-B). Acute/subacute brucellosis was diagnosed based on the presence of: (1) contact with animals or fresh animal products, (2) suggestive clinical manifestations of less than one-year duration, and (3) positive antibody titer (1:160) by standard tube agglutination test. There was no significant difference between the two groups regarding their demographic data. Fever was the most frequent manifestation (96.3%). Epigastric pain was the most frequent adverse effect of treatment (12.1%). Group-A patients had a significantly higher relapse rate compared to group-B patients (22.6% versus 9.3%, p-value=0.01). The rate of treatment adverse effects was higher among group-B patients, although not reaching statistical significance (20.4% versus 11.3%, p-value=0.059). Adding levofloxacin to the dual therapy for acute/subacute brucellosis (doxycycline-rifampin) may increase its efficacy in terms of lowering the relapse rate of the disease. Further, larger scale studies are needed before considering modifying the standard, dual therapy for brucellosis. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  2. Macrofilaricidal Activity in Wuchereria bancrofti after 2 Weeks Treatment with a Combination of Rifampicin plus Doxycycline

    Directory of Open Access Journals (Sweden)

    Alexander Yaw Debrah

    2011-01-01

    Full Text Available Infection with the filarial nematode Wuchereria bancrofti can lead to lymphedema, hydrocele, and elephantiasis. Since adult worms cause pathology in lymphatic filariasis (LF, it is imperative to discover macrofilaricidal drugs for the treatment of the infection. Endosymbiotic Wolbachia in filariae have emerged as a new target for antibiotics which can lead to macrofilaricidal effects. In Ghana, a pilot study was carried out with 39 LF-infected men; 12 were treated with 200 mg doxycycline/day for 4 weeks, 16 were treated with a combination of 200 mg doxycycline/day + 10 mg/kg/day rifampicin for 2 weeks, and 11 patients received placebo. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia, and filarial dance sign (FDS. Both 4-week doxycycline and the 2-week combination treatment reduced Wolbachia load significantly. At 18 months posttreatment, four-week doxycycline resulted in 100% adult worm loss, and the 2-week combination treatment resulted in a 50% adult worm loss. In conclusion, this pilot study with a combination of 2-week doxycycline and rifampicin demonstrates moderate macrofilaricidal activity against W. bancrofti.

  3. Doxycycline inhibits the infiltration of inflammatory cells in rat alkali burn corneas

    Directory of Open Access Journals (Sweden)

    Jing-Bo Zhao

    2013-06-01

    Full Text Available AIM: To investigate the inhibited effect of Doxycycline on the infiltration of inflammatory cells in rat alkali burn corneas. METHODS: Corneas of 32 SD rats were injured with 1mol/L NaOH, then divided into two groups: control and doxycycline-treated. All agents were administered topically 4 times daily. Slit-lamp microscope was performed and inflammatory index was calculated at 3, 7, 14 and 21 days after injury. Then 4 rats were randomly sacrificed and each cornea was divided into two parts, one for histopathology, the other for ICAM-1 ELISA assay. RESULTS:In control group, the inflammatory index and the number of inflammatory cell was higher than the doxycycline-treated dramatically at all time points(P<0.05. Compared with control group, corneal ICAM-1 expression decreased significantly in doxycycline-treated group at all time points(P < 0.05. CONCLUSION:Doxycycline may inhibit inflammatory cell infiltration by down-regulating ICAM-1 expression.

  4. Transcriptomic profiling explains racial disparities in pterygium patients treated with doxycycline.

    Science.gov (United States)

    Larrayoz, Ignacio M; Rúa, Óscar; Velilla, Sara; Martínez, Alfredo

    2014-10-30

    To understand the differential responses to doxycycline between Caucasian and Hispanic patients observed in a previous clinical trial. Primary cultures were established using pterygia excised from male Caucasian (n = 3) and Hispanic (n = 6) patients. The response of these cells to doxycycline was tested in a toxicity assay. In addition, a complete transcriptome was obtained from the nine samples, and the results were analyzed using false discovery rate statistics. Results were confirmed by quantitative RT (qRT)-PCR and Western blotting for a limited set of genes. Caucasian pterygium cells underwent apoptosis upon exposure to doxycycline, whereas Hispanic cells survived the treatment. Transcriptomic analysis showed profound differences between cells of both ethnicities, even before treatment, implicating important cellular pathways such as the mitochondrial oxidative phosphorylation chain, the proteasome, and the components of the extracellular matrix. Following exposure to doxycycline, there was a significant increase in proapoptotic proteins, regulators of the cell cycle, and components of the mitochondrial membrane in Caucasian cells but not in their Hispanic counterparts. There was a good correlation between data obtained by ultrasequencing and those generated by qRT-PCR or Western blotting. The lack of response to doxycycline observed in Hispanic pterygium patients in a previous clinical trial can be explained by the genetic protection afforded to the cells in this ethnic background against apoptosis and cell death. New therapeutic options must be devised for these patients. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  5. Doxycycline delivery from PLGA microspheres prepared by a modified solvent removal method.

    Science.gov (United States)

    Patel, Roshni S; Cho, Daniel Y; Tian, Cheng; Chang, Amy; Estrellas, Kenneth M; Lavin, Danya; Furtado, Stacia; Mathiowitz, Edith

    2012-01-01

    We report on the development of a modified solvent removal method for the encapsulation of hydrophilic drugs within poly(lactic-co-glycolic acid) (PLGA). Using a water/oil/oil double emulsion, hydrophilic doxycycline was encapsulated within PLGA spheres with particle diameters ranging from approximately 600 nm to 19 µm. Encapsulation efficiencies of up to 74% were achieved for theoretical loadings from 1% to 10% (w/w), with biphasic release over 85 days with nearly complete release at the end of this time course. About 1% salt was added to the formulations to examine its effects on doxycycline release; salt modulated release only by increasing the magnitude of initial release without altering kinetics. Fourier transform infrared spectroscopy indicated no characteristic differences between doxycycline-loaded and control spheres. Differential scanning calorimetry and X-ray diffraction suggest that there may be a molecular dispersion of the doxycycline within the spheres and the doxycycline may be in an amorphous state, which could explain the slow, prolonged release of the drug.

  6. Efficacy of single application of topical doxycycline hyclate and triamcinolone acetonide in denture adhesive in the management of recurrent aphthous stomatitis: A comparative study

    Directory of Open Access Journals (Sweden)

    Rakhi Chandak

    2017-01-01

    Conclusion: Healing of the ulcer was significantly faster with doxycycline treatment compared to triamcinolone ointment with no adverse effects. Doxycycline is proved to be one of the modalities for the treatment of aphthous ulcer.

  7. Serological Response to Treatment of Syphilis with Doxycycline Compared with Penicillin in HIV-infected Individuals

    DEFF Research Database (Denmark)

    Salado-Rasmussen, Kirsten; Hoffmann, Steen; Cowan, Susan

    2016-01-01

    Serological response to treatment of syphilis with orally administered doxycycline or intramuscularly administered penicillin was assessed in patients with concurrent HIV. All HIV-infected individuals diagnosed with syphilis attending 3 hospitals in Copenhagen, Denmark were included. Odds ratios......%) treated with doxycycline and in 8 cases (17%) treated with penicillin (OR 0.78 (95% CI 0.16-3.88), p = 0.76). The serological cure rate at 12 months was highest in patients with primary syphilis (100%), followed by patients with secondary (89%), early latent (71%) and late latent (67%) syphilis (p = 0.......006). In conclusion, this study provides evidence for the use of doxycycline as a treatment option when treating a HIV-infected population for syphilis....

  8. Doxycycline Suppresses Microglial Activation by Inhibiting the p38 MAPK and NF-kB Signaling Pathways.

    Science.gov (United States)

    Santa-Cecília, Flávia V; Socias, Benjamin; Ouidja, Mohand O; Sepulveda-Diaz, Julia E; Acuña, Leonardo; Silva, Rangel L; Michel, Patrick P; Del-Bel, Elaine; Cunha, Thiago M; Raisman-Vozari, Rita

    2016-05-01

    In neurodegenerative diseases, the inflammatory response is mediated by activated glial cells, mainly microglia, which are the resident immune cells of the central nervous system. Activated microglial cells release proinflammatory mediators and neurotoxic factors that are suspected to cause or exacerbate these diseases. We recently demonstrated that doxycycline protects substantia nigra dopaminergic neurons in an animal model of Parkinson's disease. This effect was associated with a reduction of microglial cell activation, which suggests that doxycycline may operate primarily as an anti-inflammatory drug. In the present study, we assessed the anti-inflammatory potential of doxycycline using lipopolysaccharide (LPS)-activated primary microglial cells in culture as a model of neuroinflammation. Doxycycline attenuated the expression of key activation markers in LPS-treated microglial cultures in a concentration-dependent manner. More specifically, doxycycline treatment lowered the expression of the microglial activation marker IBA-1 as well as the production of ROS, NO, and proinflammatory cytokines (TNF-α and IL-1β). In primary microglial cells, we also found that doxycycline inhibits LPS-induced p38 MAP kinase phosphorylation and NF-kB nuclear translocation. The present results indicate that the effect of doxycycline on LPS-induced microglial activation probably occurs via the modulation of p38 MAP kinase and NF-kB signaling pathways. These results support the idea that doxycycline may be useful in preventing or slowing the progression of PD and other neurodegenerative diseases that exhibit altered glia function.

  9. Inhibition of COP9-signalosome (CSN) deneddylating activity and tumor growth of diffuse large B-cell lymphomas by doxycycline.

    Science.gov (United States)

    Pulvino, Mary; Chen, Luojing; Oleksyn, David; Li, Jing; Compitello, George; Rossi, Randy; Spence, Stephen; Balakrishnan, Vijaya; Jordan, Craig; Poligone, Brian; Casulo, Carla; Burack, Richard; Shapiro, Joel L; Bernstein, Steven; Friedberg, Jonathan W; Deshaies, Raymond J; Land, Hartmut; Zhao, Jiyong

    2015-06-20

    In searching for small-molecule compounds that inhibit proliferation and survival of diffuse large B-cell lymphoma (DLBCL) cells and may, therefore, be exploited as potential therapeutic agents for this disease, we identified the commonly used and well-tolerated antibiotic doxycycline as a strong candidate. Here, we demonstrate that doxycycline inhibits the growth of DLBCL cells both in vitro and in mouse xenograft models. In addition, we show that doxycycline accumulates in DLBCL cells to high concentrations and affects multiple signaling pathways that are crucial for lymphomagenesis. Our data reveal the deneddylating activity of COP-9 signalosome (CSN) as a novel target of doxycycline and suggest that doxycycline may exert its effects in DLBCL cells in part through a CSN5-HSP90 pathway. Consistently, knockdown of CSN5 exhibited similar effects as doxycycline treatment on DLBCL cell survival and HSP90 chaperone function. In addition to DLBCL cells, doxycycline inhibited growth of several other types of non-Hodgkin lymphoma cells in vitro. Together, our results suggest that doxycycline may represent a promising therapeutic agent for DLBCL and other non-Hodgkin lymphomas subtypes.

  10. Therapeutic Efficacy and Macrofilaricidal Activity of Doxycycline for the Treatment of River Blindness

    Science.gov (United States)

    Walker, Martin; Specht, Sabine; Churcher, Thomas S.; Hoerauf, Achim; Taylor, Mark J.; Basáñez, María-Gloria

    2015-01-01

    Background. Onchocerca volvulus and lymphatic filariae, causing river blindness and elephantiasis, depend on endosymbiotic Wolbachia bacteria for growth, development, fertility, and survival. Clinical trials have shown that doxycycline treatment eliminates Wolbachia, causing long-term sterilization of adult female filariae and effecting potent macrofilaricidal activity. The continual reinfection by drug-naive worms that occurs in these trial settings dilutes observable anti-Wolbachia and antifilarial effects, making it difficult to estimate therapeutic efficacy and compare different doxycycline regimens, evaluated at different times after treatment. Methods. A meta-analytical modeling framework is developed to link all usable data collected from clinical trials measuring the Wolbachia status and viability of individual female adult worms collected at various times after treatment with 4, 5, or 6 weeks of daily 100 or 200 mg oral doxycycline. The framework is used to estimate efficacy parameters that are not directly measurable as trial outcomes. Results. The estimated efficacy of doxycycline (the maximum proportional reduction in the percentage of adult female O. volvulus positive for Wolbachia) is 91%–94% on average, irrespective of the treatment regimen. Efficacy is >95% in the majority of trial participants. The life span of Wolbachia-depleted worms is reduced by 70%–80%, from approximately 10 years to 2–3 years. Conclusions. The efficacy parameters are pertinent to the prospects of using doxycycline on a “test and treat” basis for onchocerciasis control and confirm doxycycline as a potent macrofilaricidal therapy. The modeling approach is more generally relevant to the design and evaluation of clinical trials for antifilarial drugs conducted in endemic settings. PMID:25537873

  11. Interference of doxycycline pretreatment in a model of abdominal aortic aneurysms.

    Science.gov (United States)

    Mata, Karina M; Tefé-Silva, Cristiane; Floriano, Elaine M; Fernandes, Cleverson R; Rizzi, Elen; Gerlach, Raquel F; Mazzuca, Marc Q; Ramos, Simone G

    2015-01-01

    Abdominal aortic aneurysm (AAA) is characterized by chronic inflammation and degradation of the extracellular matrix, mediated by matrix metalloproteinases (MMPs). Doxycycline has been reported to control the progression of AAA by regulation of MMP. We hypothesized that doxycycline pretreatment in a rat model of AAA would cause reduction in gelatinolytic activity of MMP-2 and -9 and the inflammatory response in the wall of an aneurysm, consequently decreasing the formation and development of AAAs. Male Wistar rats were divided into the following four groups: aneurysm (A); control (C); aneurysm+doxycycline (A+D) and control+doxycycline (C+D), with 24 animals per group subdivided into n=6 animals at different time points [1, 3, 7, and 15 days postsurgery (dps)]. The (A) and (A+D) groups simultaneously received the injury and extrinsic stenosis of the aortic wall. The (C) and (C+D) groups received sham operation. The treated animals received doxycycline via gavage (30 mg/kg/day) from 48 h before surgery until the end of experiment. At 1, 3, 7, and 15 dps, the animals were euthanized, and the aortas were collected for morphological analyses, immunohistochemistry, and zymography. The animals from the (A) group developed AAAs. However, the animals treated with doxycycline showed a 85% decrease in AAA development, which was associated with a large reduction in gelatinolytic activity of MMP-2 and -9, and decreased inflammatory response (Pdoxycycline before surgery inhibited the activity of MMP-2 and -9, as well as the inflammatory response, and may play an important role in the prevention of the development of AAAs. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections, with focus on doxycycline.

    Science.gov (United States)

    Hamad, Tarza; Hellmark, Bengt; Nilsdotter-Augustinsson, Åsa; Söderquist, Bo

    2015-12-01

    In recent years, coagulase-negative staphylococci such as Staphylococcus epidermidis have gained importance as nosocomial pathogens, especially in immunocompromised patients and prosthetic joint infections (PJIs). These infections are often long lasting and difficult to treat due to the production of bacterial biofilm and the transformation of the bacteria into a stationary growth phase. Rifampicin is able to penetrate the biofilm, but to reduce the risk of development of rifampicin resistance it should be used in combination with an additional antibiotic. In this study we used Etest to investigate the antimicrobial susceptibility of 134 clinical isolates of S. epidermidis obtained from PJIs to six oral antibiotics: doxycycline, rifampicin, linezolid, fusidic acid, clindamycin, and ciprofloxacin. We also performed synergy testing on doxycycline in combination with each of the remaining antibiotics. Ninety-three (69%) of the 134 isolates were susceptible to doxycycline, 94/134 (70%) to rifampicin, 56/134 (42%) to clindamycin, 25/134 (19%) to ciprofloxacin, 81/134 (60%) to fusidic acid, and 100% to linezolid. Thirty-two (80%) of the 40 isolates not fully susceptible to rifampicin were susceptible to doxycycline. Doxycycline in combination with each of the other investigated antibiotics exerted an additive effect on nearly half of the isolates, with the exception of clindamycin, which displayed an even higher percentage of additive effect (69%). To conclude, as the majority of the S. epidermidis isolates were susceptible to doxycycline, this antimicrobial agent may provide a potential alternative for combination therapy together with rifampicin. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  13. Doxycycline in early CJD: a double-blinded randomised phase II and observational study.

    Science.gov (United States)

    Varges, Daniela; Manthey, Henrike; Heinemann, Uta; Ponto, Claudia; Schmitz, Matthias; Schulz-Schaeffer, Walter J; Krasnianski, Anna; Breithaupt, Maren; Fincke, Fabian; Kramer, Katharina; Friede, Tim; Zerr, Inga

    2017-02-01

    The main objective of the present study is to study the therapeutic efficiency of doxycycline in a double-blinded randomised phase II study in a cohort of patients with sporadic Creutzfeldt-Jakob disease (sCJD). From the National Reference Center of TSE Surveillance in Germany, patients with probable or definite sCJD were recruited for a double-blinded randomised study with oral doxycycline (EudraCT 2006-003934-14). In addition, we analysed the data from patients with CJD who received compassionate treatment with doxycycline in a separate group. Potential factors which influence survival such as age at onset, gender, codon 129 polymorphism and cognitive functions were evaluated. The primary outcome measure was survival. Group 1: in the double-blinded randomised phase II study, 7 patients in the treatment group were compared with 5 controls. Group 2: 55 patients with sCJD treated with oral doxycycline were analysed and compared with 33 controls by a stratified propensity score applied to a Cox proportional hazard analysis. The results of both studies were combined by means of a random-effects meta-analysis. A slight increase in survival time in the doxycycline treatment group was observed (p=0.049, HR=0.63 (95% CI 0.402 to 0.999)). On the basis of our studies, a larger trial of doxycycline should be performed in persons in the earliest stages of CJD. EudraCT 2006-003934-14; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. Therapeutic efficacy and macrofilaricidal activity of doxycycline for the treatment of river blindness.

    Science.gov (United States)

    Walker, Martin; Specht, Sabine; Churcher, Thomas S; Hoerauf, Achim; Taylor, Mark J; Basáñez, María-Gloria

    2015-04-15

    Onchocerca volvulus and lymphatic filariae, causing river blindness and elephantiasis, depend on endosymbiotic Wolbachia bacteria for growth, development, fertility, and survival. Clinical trials have shown that doxycycline treatment eliminates Wolbachia, causing long-term sterilization of adult female filariae and effecting potent macrofilaricidal activity. The continual reinfection by drug-naive worms that occurs in these trial settings dilutes observable anti-Wolbachia and antifilarial effects, making it difficult to estimate therapeutic efficacy and compare different doxycycline regimens, evaluated at different times after treatment. A meta-analytical modeling framework is developed to link all usable data collected from clinical trials measuring the Wolbachia status and viability of individual female adult worms collected at various times after treatment with 4, 5, or 6 weeks of daily 100 or 200 mg oral doxycycline. The framework is used to estimate efficacy parameters that are not directly measurable as trial outcomes. The estimated efficacy of doxycycline (the maximum proportional reduction in the percentage of adult female O. volvulus positive for Wolbachia) is 91%-94% on average, irrespective of the treatment regimen. Efficacy is >95% in the majority of trial participants. The life span of Wolbachia-depleted worms is reduced by 70%-80%, from approximately 10 years to 2-3 years. The efficacy parameters are pertinent to the prospects of using doxycycline on a "test and treat" basis for onchocerciasis control and confirm doxycycline as a potent macrofilaricidal therapy. The modeling approach is more generally relevant to the design and evaluation of clinical trials for antifilarial drugs conducted in endemic settings. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  15. Management of nonsexually acquired genital ulceration using oral and topical corticosteroids followed by doxycycline prophylaxis.

    Science.gov (United States)

    Dixit, Shreya; Bradford, Jennifer; Fischer, Gayle

    2013-05-01

    Data regarding the treatment of nonsexually acquired genital ulceration (NSAGU) are limited. We sought to provide evidence for the safety and efficacy of topical and systemic corticosteroids followed by doxycycline prophylaxis for acute and recurrent NSAGU. A retrospective chart review was conducted of patients with NSAGU treated in a private dermogynecology practice. A total of 26 girls and women with NSAGU were identified and divided into 2 groups: group A = 17 patients with moderate to severe ulceration treated in the acute stage with oral corticosteroid; and group B = 9 patients with mild ulceration treated in the acute stage with topical corticosteroid. Patients in group A, with a mean age of 27.9 years (range, 11-62 years), were treated with oral prednisolone commencing with 15 to 50 mg per day depending on severity. Sixteen (94%) achieved rapid pain relief and complete healing of ulcers within 16 days. Eight (47%) commenced doxycycline prophylaxis. Women in group B, with a mean age of 42.5 years (range, 26-67 years) were treated with topical corticosteroids. Eight (89%) had a history of recurrent ulcers and 6 (66%) commenced doxycycline prophylaxis. Of all 14 patients on doxycycline prophylaxis, none reported any recurrences during a mean follow-up of 18.3 months. There were no adverse effects caused by prednisolone. One patient experienced mild photosensitivity from doxycycline but continued to take it. This was a retrospective case series from a single private practice-based population. Topical or oral corticosteroids followed by prophylactic doxycycline can be effective in rapidly resolving acute flareups and preventing recurrences of NSAGU. All patients responded to therapy without treatment-limiting side effects. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  16. Effects of matrix metalloproteinase inhibitor doxycycline and CD147 antagonist peptide-9 on gallbladder carcinoma cell lines.

    Science.gov (United States)

    Wang, Shihang; Liu, Chao; Liu, Xinjiang; He, Yanxin; Shen, Dongfang; Luo, Qiankun; Dong, Yuxi; Dong, Haifeng; Pang, Zhigang

    2017-10-01

    Gallbladder carcinoma is the most common and aggressive malignancy of the biliary tree and highly expresses CD147, which is closely related to disease prognosis in a variety of human cancers. Doxycycline exhibited anti-tumor properties in many cancer cells. CD147 antagonist peptide-9 is a polypeptide and can specifically bind to CD147. The effect of these two drugs on gallbladder cancer cells has not been studied. The aim of this study is to investigate the effect of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells and the possible mechanism of inhibition on cancer cell of doxycycline. To investigate the effects of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells (GBC-SD and SGC-996), cell proliferation, CD147 expression, and early-stage apoptosis rate were measured after treated with doxycycline. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were measured after treated with different concentrations of doxycycline, antagonist peptide-9, and their combination. The results demonstrated that doxycycline inhibited cell proliferation, reduced CD147 expression level, and induced an early-stage apoptosis response in GBC-SD and SGC-996 cells. The matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were inhibited by antagonist peptide-9 and doxycycline, and the inhibitory effects were enhanced by combined drugs in gallbladder carcinoma cell lines. Taken together, doxycycline showed inhibitory effects on gallbladder carcinoma cell lines and reduced the expression of CD147, and this may be the mechanism by which doxycycline inhibits cancer cells. This study provides new information and tries to implement the design of adjuvant therapy method for gallbladder carcinoma.

  17. Doxycycline therapy for abdominal aneurysm: Improved proteolytic balance through reduced neutrophil content

    NARCIS (Netherlands)

    Abdul-Hussien, H.; Hanemaaijer, R.; Verheijen, J.H.; Bockel, J.H. van; Geelkerken, R.H.; Lindeman, J.H.N.

    2009-01-01

    Background: Matrix metalloproteinase-9 (MMP-9) is thought to play a central role in abdominal aortic aneurysm (AAA) initiation. Doxycycline, a tetracycline analogue, has direct MMP-9-inhibiting properties in vitro, and it effectively suppresses AAA development in rodents. Observed inhibition of AAA

  18. Doxycycline Inhibits Vascular Leakage and Prevents the Development of Pulmonary Edema

    Science.gov (United States)

    2008-12-01

    and have been used to reduce tissue degradation in arthritis and periodontal disease (Golub; Lee et al. 1998). Doxycycline, a tetracycline derivative...lining blood vessels serves as a barrier against vascular hyperpermeability, and its maintenance is critical to organ health. Inflammatory mediators

  19. Potential for Enhanced Therapeutic Activity of Biological Cancer Therapies with Doxycycline Combination

    Science.gov (United States)

    Tang, Hui; Sampath, Padma; Yan, Xinmin; Thorne, Stephen H

    2012-01-01

    Despite significant strides made in the clinical translation of adoptive immune cell therapies, it is apparent that many tumors incorporate strategies to avoid recognition by receptors expressed on the immune cells, such as NKG2D. Strategies that stabilize the expression of ligands for these receptors may enhance the therapeutic potential of these and related therapies. Doxycycline inhibits matrix metalloproteinases (MMPs) that act to cleave the extracellular domain of MICA/B, ligands for the NKG2D receptor. Doxycycline treatment blocked shedding of MICA/B from a panel of human tumor cells, but also acted to increase their expression and cell surface translocation, possibly through its action on ATM. This meant that many tumor cells displayed increased MICA/B expression and enhanced susceptibility to CIK cells. Interestingly, doxycycline also selectively enhanced the replication of oncolytic vaccinia in many tumor cell lines, leading to increased sensitivity to these therapies. Combination (CIK-oncolytic vaccinia) therapies used in conjunction with doxycyline led to increased anti-tumor effects. The unexpected and pleiotropic beneficial anti-tumor effects of doxycycline on both immune cell and oncolytic viral therapies make it an excellent candidate for rapid clinical testing. PMID:23282955

  20. Lack of doxycycline antimalarial prophylaxis impact on Staphylococcus aureus tetracycline resistance.

    Science.gov (United States)

    Mende, Katrin; Beckius, Miriam L; Zera, Wendy C; Yu, Xin; Li, Ping; Tribble, David R; Murray, Clinton K

    2016-10-01

    There is concern that susceptibility of Staphylococcus aureus to tetracyclines may decrease due to use of antimalarial prophylaxis (doxycycline). We examined characteristics related to tetracycline resistance, including doxycycline exposure, in S. aureus isolates collected via admission surveillance swabs and inpatient clinical cultures from United States military personnel injured during deployment (June 2009-January 2012). Tetracycline class resistance was determined using antimicrobial susceptibility testing. The first S. aureus isolate from 168 patients were analyzed, of which 38 (23%) isolates were resistant to tetracyclines (class). Tetracycline-resistant isolates had a higher proportion of resistance to clindamycin (P=0.019) compared to susceptible isolates. There was no significant difference in tetracycline resistance between isolates collected from patients with and without antimalarial prophylaxis; however, significantly more isolates had tet(M) resistance genes in the doxycycline exposure group (P=0.031). Despite 55% of the patients receiving doxycycline as antimalarial prophylaxis, there was no association with resistance to tetracyclines. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Simple colorimetric detection of doxycycline and oxytetracycline using unmodified gold nanoparticles

    Science.gov (United States)

    Li, Jie; Fan, Shumin; Li, Zhigang; Xie, Yuanzhe; Wang, Rui; Ge, Baoyu; Wu, Jing; Wang, Ruiyong

    2014-08-01

    The interaction between tetracycline antibiotics and gold nanoparticles was studied. With citrate-coated gold nanoparticles as colorimetric probe, a simple and rapid detection method for doxycycline and oxytetracycline has been developed. This method relies on the distance-dependent optical properties of gold nanoparticles. In weakly acidic buffer medium, doxycycline and oxytetracycline could rapidly induce the aggregation of gold nanoparticles, resulting in red-to-blue (or purple) colour change. The experimental parameters were optimized with regard to pH, the concentration of the gold nanoparticles and the reaction time. Under optimal experimental conditions, the linear range of the colorimetric sensor for doxycycline/oxytetracycline was 0.06-0.66 and 0.59-8.85 μg mL-1, respectively. The corresponding limit of detection for doxycycline and oxytetracycline was 0.0086 and 0.0838 μg mL-1, respectively. This assay was sensitive, selective, simple and readily used to detect tetracycline antibiotics in food products.

  2. Sealing ability of mineral trioxide aggregate (MTA) combined with distilled water, chlorhexidine, and doxycycline.

    Science.gov (United States)

    Arruda, Roberta A A; Cunha, Rodrigo S; Miguita, Kenner B; Silveira, Cláudia F M; De Martin, Alexandre S; Pinheiro, Sérgio L; Rocha, Daniel G P; Bueno, Carlos E S

    2012-09-01

    The aim of this study was to evaluate the sealing ability of mineral trioxide aggregate (MTA Bio) combined with different mixing agents (distilled water, chlorhexidine, doxycycline), used as an apical root-end filling material. Forty-two extracted human teeth were divided into three groups (n = 12); six teeth were used as controls. Root-ends were resected at 90 degrees, 3 mm from the apex. Root-end cavities were prepared using ultrasonic tips and filled with MTA Bio plus distilled water, 2% chlorhexidine solution, or 10% doxycycline solution. Apical sealing was assessed by microleakage of 50% silver nitrate solution. Roots were longitudinally sectioned in a buccolingual plane and analyzed using an operating microscope (20× magnification). Depth of dye leakage into the dentinal walls was measured in millimeters. Results were analyzed using ANOVA and Tukey's test (P = 0.05). MTA Bio plus distilled water showed significantly higher mean leakage results (1.06 mm) when compared with MTA Bio plus doxycycline (0.61 mm), and higher, although not significant, results when compared with MTA Bio plus chlorhexidine (0.79 mm). In conclusion, replacing distilled water with two biologically active mixing agents (doxycycline and chlorhexidine) did not alter the sealing properties of MTABio. The antimicrobial properties of these combinations should be further investigated.

  3. DsRed gene expression by doxycycline in porcine fibroblasts and ...

    African Journals Online (AJOL)

    DsRed gene expression by doxycycline in porcine fibroblasts and cloned embryos using transposon. SuJin Kim, JoonHo Moon, BegoRoibas da Torre, Islam M Saadeldin, JungTaek Kang, JiYei Choi, SolJi Park, Byeong-Chun Lee, Goo Jang Goo Jang ...

  4. 76 FR 44926 - Renewal of Declaration Regarding Emergency Use of Doxycycline Hyclate Tablets Accompanied by...

    Science.gov (United States)

    2011-07-27

    ... and Amendment To Include All Oral Formulations of Doxycycline AGENCY: Office of the Secretary (OS...-3(a) and amending the declaration to include all oral formulations of doxycyline accompanied by... the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 360bbb-3(b)(4). DATES: This Notice and referenced...

  5. 76 FR 47197 - Authorization of Emergency Use of Oral Formulations of Doxycycline; Availability

    Science.gov (United States)

    2011-08-04

    ... HUMAN SERVICES Food and Drug Administration Authorization of Emergency Use of Oral Formulations of... Authorization) for oral formulations of doxycycline for the post-exposure prophylaxis of inhalational anthrax... this Authorization under the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as requested by the...

  6. In vitro release of doxycycline from bioabsorbable materials and acrylic strips

    DEFF Research Database (Denmark)

    Larsen, T

    1990-01-01

    Treatment of marginal periodontitis may include use of local antibiotics. In the present in vitro study the bioabsorbable materials Surgicel, Tissell, and CollaCote and acrylic strips were examined for release of doxycycline into liquids and residual antibacterial activity of the materials. Piece...

  7. Inhibition of extracellular matrix production and remodeling by doxycycline in smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Rogelio Palomino-Morales

    2016-12-01

    Full Text Available Alterations in the extracellular matrix (ECM production and remodeling of smooth muscle cells (SMCs have been implicated in processes related to the differentiation in atherosclerosis. Due to the anti-atherosclerotic properties of the tetracyclines, we aimed to investigate whether cholesterol supplementation changes the effect of doxycycline over the ECM proteins synthesis and whether isoprenylated proteins and Rho A protein activation are affected. SMC primary culture isolated from chicks exposed to atherogenic factors in vivo (a cholesterol-rich diet, SMC-Ch, comparing it with control cultures isolated after a standard diet (SMC-C. After treatment with 20 nM doxycycline, [H3]-proline and [H3]-mevalonate incorporation were used to measure the synthesis of collagen and isoprenylated proteins, respectively. Real-time PCR was assessed to determine col1a2, col2a1, col3a1, fibronectin, and mmp2 gene expression and the pull-down technique was applied to determine the Rho A activation state. A higher synthesis of collagens and isoprenylated proteins in SMC-Ch than in SMC-C was determined showing that doxycycline inhibits ECM production and remodeling in both SMC types of cultures. Moreover, preliminary results about the effect of doxycycline on protein isoprenylation and Rho A protein activation led us to discuss the possibility that membrane G-protein activation pathways could mediate the molecular mechanism.

  8. Effect of addition of 2% chlorhexidine or 10% doxycycline on antimicrobial activity of biodentine.

    Science.gov (United States)

    Nikhil, Vineeta; Madan, Molly; Agarwal, Charu; Suri, Navleen

    2014-05-01

    The purpose of this in vitro study was to determine whether the addition of 2% chlorhexidine gluconate or 10% doxycycline would enhance the antimicrobial activity of Biodentine against Staphylococcus aureus (ATCC-25923), Enterococcus faecalis (ATCC-29212), Candida albicans (ATCC-90028), and Streptococcus mutans (MTCC-497). Three wells of 4 mm diameter and 4 mm depth on each plate were prepared on the agar medium with standardized suspensions of each microorganism. Biodentine powder mixed with 2% chlorhexidine (0.06 g) or 10% doxycycline (0.30 g) in its liquid or liquid alone was placed to fill each well. Plates were incubated at 37°C as required for microbial growth. A blinded, independent observer measured zones of inhibition. The data were analyzed using independent "t" test to compare the differences among the three cement preparations for different micro-organisms. All Biodentine samples inhibited microbial growth. The highest mean diameters of zone of inhibition for all the micro-organisms were found around Biodentine/chlorhexidine (13.417) followed by Biodentine alone (12.236) and Biodentine/doxycycline (11.25). In conclusion, adding 2% chlorhexidine gluconate in liquid of Biodentine enhanced the antimicrobial activity of Biodentine against all the tested micro-organisms except Candida albicans, while addition of 10% doxycycline decreased the antimicrobial activity of Biodentine. The differences were significant statistically (P < 0.05).

  9. Pharmacodynamics of doxycycline and tetracycline against Staphylococcus pseudintermedius

    DEFF Research Database (Denmark)

    Maaland, Marit Gaastra; Papich, Mark G.; Turnidge, John

    2013-01-01

    doxycycline susceptibility of Staphylococcus pseudintermedius.MICs and inhibition zone diameters were determined according to CLSI standards in 168 canine S. pseudintermedius isolates. Tetracycline resistance genes were detected by PCR, and time-kill curves were determined for representative strains. In vitro...

  10. Inhibition of extracellular matrix production and remodeling by doxycycline in smooth muscle cells.

    Science.gov (United States)

    Palomino-Morales, Rogelio; Torres, Carolina; Perales, Sonia; Linares, Ana; Alejandre, Maria Jose

    2016-12-01

    Alterations in the extracellular matrix (ECM) production and remodeling of smooth muscle cells (SMCs) have been implicated in processes related to the differentiation in atherosclerosis. Due to the anti-atherosclerotic properties of the tetracyclines, we aimed to investigate whether cholesterol supplementation changes the effect of doxycycline over the ECM proteins synthesis and whether isoprenylated proteins and Rho A protein activation are affected. SMC primary culture isolated from chicks exposed to atherogenic factors in vivo (a cholesterol-rich diet, SMC-Ch), comparing it with control cultures isolated after a standard diet (SMC-C). After treatment with 20 nM doxycycline, [H3]-proline and [H3]-mevalonate incorporation were used to measure the synthesis of collagen and isoprenylated proteins, respectively. Real-time PCR was assessed to determine col1a2, col2a1, col3a1, fibronectin, and mmp2 gene expression and the pull-down technique was applied to determine the Rho A activation state. A higher synthesis of collagens and isoprenylated proteins in SMC-Ch than in SMC-C was determined showing that doxycycline inhibits ECM production and remodeling in both SMC types of cultures. Moreover, preliminary results about the effect of doxycycline on protein isoprenylation and Rho A protein activation led us to discuss the possibility that membrane G-protein activation pathways could mediate the molecular mechanism. Copyright © 2016 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  11. The cre-inducer doxycycline lowers cytokine and chemokine transcript levels in the gut of mice

    DEFF Research Database (Denmark)

    Hansen, Axel Kornerup; Malm, Sara Astrup; Metzdorff, Stine B.

    2017-01-01

    a strong impact on the immune system. Here we show that in C57BL/6 mice, the most commonly applied strain for genetic modification, doxycycline treatment lowered transcription of the genes Il1b, Il10, Il18, Tnf, Cxcl1, and Cxcl2 in the ileum, and of the gene Il18 in colon. Cytokines and chemokines encoded...

  12. Doxycycline supplementation allows for the culture of human ESCs/iPSCs with media changes at 3-day intervals.

    Science.gov (United States)

    Chang, Mi-Yoon; Oh, Boram; Rhee, Yong-Hee; Lee, Sang-Hun

    2015-11-01

    Culturing human embryonic stem and induced pluripotent stem cells (hESCs/iPSCs) is one of the most costly and labor-intensive tissue cultures, as media containing expensive factors/cytokines should be changed every day to maintain and propagate undifferentiated hESCs/iPSCs in vitro. We recently reported that doxycycline, an anti-bacterial agent, had dramatic effects on hESC/iPSC survival and promoted self-renewal. In this study, we extended the effects of doxycycline to a more practical issue to save cost and labor in hESC/iPSC cultures. Regardless of cultured cell conditions, hESCs/iPSCs in doxycycline-supplemented media were viable and proliferating for at least 3 days without media change, while none or few viable cells were detected in the absence of doxycycline in the same conditions. Thus, hESCs/iPSCs supplemented with doxycycline can be cultured for a long period of time with media changes at 3-day intervals without altering their self-renewal and pluripotent properties, indicating that doxycycline supplementation can reduce the frequency of media changes and the amount of media required by 1/3. These findings strongly encourage the use of doxycycline to save cost and labor in culturing hESCs/iPSCs. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  13. The role of doxycycline in the therapy of multidrug-resistant E. coli - an in vitro study.

    Science.gov (United States)

    Lai, Chih-Cheng; Chen, Chi-Chung; Huang, Hui-Ling; Chuang, Yin-Ching; Tang, Hung-Jen

    2016-08-18

    This study assessed the in vitro antibacterial activity of combinations of amikacin and doxycycline or tigecycline against multidrug-resistant E. coli isolates. Twenty-four different pulsotypes, including 10 extended-spectrum β-lactamase (ESBL)-, 10 carbapenem-resistant, 2 New Delhi Metallo-beta-lactamase (NDM)- and 2 Klebsiella pneumoniae carbapenemase (KPC)-E. coli isolates were collected. All 24 isolates were susceptible to amikacin and tigecycline. Only 30% of ESBL and 50% of carbapenem-resistant E. coli were susceptible to doxycycline. Both of the NDM-E. coli had a MIC of 64 μg/ml. The checkerboard method showed that for the ESBL- and carbapenem-resistant E. coli, the synergistic effects of amikacin/doxycycline were 80% and 90%, respectively. For the two KPC- and two NDM-E. coli, the FIC index of amikacin/doxycycline were 0.5/0.375 and 0.5/0.281, respectively. For the ESBL- and carbapenem-resistant E. coli isolates, the combinations of amikacin and doxycycline exhibited synergistic activities against 80%, and 80% and 10% vs 60%, and 80% and 10% of the isolates at concentrations of 1x, 1/2x and 1/4xMIC, respectively. The synergistic effect seems to be similar for doxycycline and tigecycline based combinations with amikacin. In conclusion, the antibacterial activity of doxycycline can be enhanced by the addition of amikacin and is observed against most multidrug-resistant E. coli isolates.

  14. Long term impact of large scale community-directed delivery of doxycycline for the treatment of onchocerciasis

    Directory of Open Access Journals (Sweden)

    Tamarozzi Francesca

    2012-03-01

    Full Text Available Abstract Background Anti-Wolbachia treatment with doxycycline is effective in sterilising and killing adult Onchocerca volvulus nematodes, proving superior to ivermectin and of great potential as an alternative approach for the treatment and control of onchocerciasis, particularly in areas of Loa loa co-endemicity. Nevertheless, the length of the required treatment poses potential logistical problems and risk of poor compliance, raising a barrier to the use of doxycycline in Mass Drug Administration (MDA strategies. In 2007 and 2008 a feasibility trial of community-directed treatment with doxycycline was carried out in two health districts in Cameroon, co-endemic for O. volvulus and L. loa. With 17,519 eligible subjects, the therapeutic coverage was 73.8% with 97.5% compliance, encouraging the feasibility of using doxycycline community-directed delivery in restricted populations of this size. The current study evaluated the effectiveness of this community-directed delivery of doxycycline four years after delivery. Findings Infection with O. volvulus was evaluated by skin biopsy and nodule palpation. Of the 507 subjects recruited, 375 had completed the treatment with doxycycline followed by one or two rounds of annual ivermectin MDA and 132 received one or two rounds of annual ivermectin MDA alone. Statistically significant lower microfilarial prevalence (17.0% [doxycycline plus ivermectin group], 27.0% [ivermectin only group], p = 0.014 and load (p = 0.012 were found in people that had received doxycycline followed by ivermectin compared to those who received ivermectin only. Conclusions This study demonstrates the long-term effectiveness of doxycycline treatment delivered with a community-directed strategy even when evaluated four years after delivery in an area of ongoing transmission. This finding shows that a multi-week course of treatment is not a barrier to community-delivery of MDA in restricted populations of this size and supports its

  15. Combination of amikacin and doxycycline against multidrug-resistant and extensively drug-resistant tuberculosis.

    Science.gov (United States)

    Gonzalo, Ximena; Casali, Nicola; Broda, Agnieszka; Pardieu, Claire; Drobniewski, Francis

    2015-04-01

    The objective of this study was to assess the activity of amikacin in combination with doxycycline against clinical strains of Mycobacterium tuberculosis in the search for new strategies against multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. The study included 28 clinical M. tuberculosis strains, comprising 5 fully susceptible, 1 isoniazid-resistant, 17 MDR, 1 poly-resistant (streptomycin/isoniazid), 1 rifampicin-resistant and 3 XDR isolates, as well as the laboratory strain M. tuberculosis H37Rv. Minimum inhibitory concentrations (MICs) were determined using a modified chequerboard methodology in a BACTEC™ MGIT™ 960 System. Fractional inhibitory concentration indices (FICIs) were calculated, and synergy, indifference or antagonism was assessed. Whole-genome sequencing was performed to investigate the genetic basis of synergy, indifference or antagonism. The MIC50 and MIC90 values (MICs that inhibit 50% and 90% of the isolates, respectively) were, respectively, 0.5 mg/L and 1.0 mg/L for amikacin and 8 mg/L and 16 mg/L for doxycycline. The combination of amikacin and doxycycline showed a synergistic effect in 18 of the 29 strains tested and indifference in 11 strains. Antagonism was not observed. A streptomycin resistance mutation (K43R) was associated with indifference. In conclusion, the benefit of addition of doxycycline to an amikacin-containing regimen should be explored since in vitro results in this study indicate either synergy or indifference. Moreover, doxycycline also has immunomodulatory effects. Copyright © 2015. Published by Elsevier B.V.

  16. Comparing efficacy of Montelukast versus doxycycline in treatment of moderate acne.

    Science.gov (United States)

    Behrangi, Elham; Arasteh, Elahe; Tavakoli, Tahmine; Mehran, Golnaz; Atefi, Najmolsadat; Esmaeeli, Shooka; Azizian, Zahra

    2015-04-01

    Treatment of acne is an important issue for reducing the cosmetic and psychological burden of disease. Regarding the inflammatory effect of LT-B4 in acne lesions and action mechanism of Montelukast, this study was performed to determine the efficacy of Montelukastin acne treatment comparison with doxycycline. In a randomized clinical trial that was performed in Dermatology Clinic in a Training Tertiary Health Care Center in Tehran, Iran since January 2012 to May 2014, 52 patients with moderate acne were evaluated. The included patients were randomly assigned to receive doxycycline 100 mg/day plus 1% Clindamycin solution (Group 1) or Montelukast 5 mg daily plus 1% clindamycin solution (Group 2). The acne severity index was measured and compared between two groups at baseline (on admission), 1-month and 3 months later. Independent-Sample-T, Chi-Square, and Repeated-Measure ANOVA tests were used and were considered statistically significant at P Montelukast and doxycycline group, respectively (P = 0.679). The mean acne severity index after 1-month was 10.5 ± 6.2 and 12.9 ± 3.3 in Montelukast and doxycycline group, respectively (P = 0). Finally, the mean acne severity index after 3 months follow-up was 8.6 ± 4.8 and 8.2 ± 1.2 in Montelukast and doxycycline group, respectively (P = 0.01). There was no significant difference between two groups regarding the amount of decrease in acne severity index across the study (P = 0.186). However, each groups showed a significant reduction in the acne severity index, separately (P = 0.001). It may be concluded that Montelukast is an effective and safe medication for moderate-level acne treatment.

  17. Treatment of ocular rosacea:comparative study of topical cyclosporine and oral doxycycline

    Directory of Open Access Journals (Sweden)

    Aysegul Arman

    2015-06-01

    Full Text Available AIM:To compare the effectiveness of topical cyclosporine A emulsion with that of oral doxycycline for rosacea associated ocular changes and dry eye complaints.METHODS:One hundred and ten patients with rosacea were screened. Thirty-eight patients having rosacea associated eyelid and ocular surface changes and dry eye complaints were included in the study. Patients were randomly divided into two groups:nineteen patients were given topical cyclosporine twice daily and nineteen patients were given oral doxycycline 100 mg twice daily for the first month and once daily for the following two months. Symptom and sign scores, ocular surface disease index questionnarie and tear function tests were evaluated at baseline and monthly for 3mo. Three months after results were compared with that of baseline.RESULTS:Mean values of symptom, eyelid sign and corneal/conjunctival sign scores of each treatment group at baseline and 3mo after treatments were compared and both drugs were found to be effective on rosacea associated ocular changes (P<0.001. Cyclosporine was more effective in symptomatic relief and in the treatment of eyelid signs (P=0.01. There was statistically significant increase in the mean Schirmer score with anesthesia and tear break up time scores in the cyclosporine treatment group compared to the doxycycline treatment group (P<0.05.CONCLUSION:Cyclosporine as a topical drug can be used in the treatment of rosacea associated ocular complications because it is more effective than doxycycline. In addition ocular rosacea as a chronic disease requires long term treatment and doxycycline has various side effects limiting its long term usage.

  18. A rapid and sensitive assay for determination of doxycycline using thioglycolic acid-capped cadmium telluride quantum dots

    Science.gov (United States)

    Tashkhourian, Javad; Absalan, Ghodratollah; Jafari, Marzieh; Zare, Saber

    2016-01-01

    A rapid, simple and inexpensive spectrofluorimetric sensor for determination of doxycycline based on its interaction with thioglycolic acid-capped cadmium telluride quantum dots (TGA/CdTe QDs) has been developed. Under the optimum experimental conditions, the sensor exhibited a fast response time of determination of doxycycline in a concentration range of 1.9 × 10-6-6.1 × 10-5 mol L-1 with a detection limit of 1.1 × 10-7 mol L-1. The sensor was applied for determination of doxycycline in honey and human serum samples.

  19. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

    Energy Technology Data Exchange (ETDEWEB)

    Tewari-Singh, Neera, E-mail: Neera.Tewari-Singh@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Jain, Anil K., E-mail: Anil.Jain@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Inturi, Swetha, E-mail: Swetha.Inturi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Ammar, David A., E-mail: David.Ammar@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Chapla, E-mail: Chapla.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Tyagi, Puneet, E-mail: Puneet.Tyagi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Kompella, Uday B., E-mail: Uday.Kompella@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Enzenauer, Robert W., E-mail: Robert.Enzenauer@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Petrash, J. Mark, E-mail: Mark.Petrash@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Rajesh, E-mail: Rajesh.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States)

    2012-10-01

    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

  20. Clonal expansion of T cells in abdominal aortic aneurysm: a role for doxycycline as drug of choice?

    Science.gov (United States)

    Kroon, Albert M; Taanman, Jan-Willem

    2015-05-18

    Most reported studies with animal models of abdominal aortic aneurysm (AAA) and several studies with patients have suggested that doxycycline favourably modifies AAA; however, a recent large long-term clinical trial found that doxycycline did not limit aneurysm growth. Thus, there is currently no convincing evidence that doxycycline reduces AAA expansion. Here, we critically review the available experimental and clinical information about the effects of doxycycline when used as a pharmacological treatment for AAA. The view that AAA can be considered an autoimmune disease and the observation that AAA tissue shows clonal expansion of T cells is placed in the light of the well-known inhibition of mitochondrial protein synthesis by doxycycline. In T cell leukaemia animal models, this inhibitory effect of the antibiotic has been shown to impede T cell proliferation, resulting in complete tumour eradication. We suggest that the available evidence of doxycycline action on AAA is erroneously ascribed to its inhibition of matrix metalloproteinases (MMPs) by competitive binding of the zinc ion co-factor. Although competitive binding may explain the inhibition of proteolytic activity, it does not explain the observed decreases of MMP mRNA levels. We propose that the observed effects of doxycycline are secondary to inhibition of mitochondrial protein synthesis. Provided that serum doxycycline levels are kept at adequate levels, the inhibition will result in a proliferation arrest, especially of clonally expanding T cells. This, in turn, leads to the decrease of proinflammatory cytokines that are normally generated by these cells. The drastic change in cell type composition may explain the changes in MMP mRNA and protein levels in the tissue samples.

  1. Association of doxycycline use with the development of gastroenteritis, irritable bowel syndrome and inflammatory bowel disease in Australians deployed abroad.

    Science.gov (United States)

    Lee, T W; Russell, L; Deng, M; Gibson, P R

    2013-08-01

    The risks are unknown for developing chronic gastrointestinal illness when personnel are relocated short term to other countries and when taking antibiotic prophylaxis in areas where malaria is endemic. To examine the associations of deployment to developed or developing countries and exposure to doxycycline with the new onset of acute gastroenteritis, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). A cross-sectional web-based survey of all current and past members of the Australian Federal Police Association was undertaken. Independent predictors of gastrointestinal illness were examined by logistic regression analysis relative to those not deployed without exposure to doxycycline. Of 1300 respondents (response rate 34%), 133 were excluded due to pre-existing chronic gastrointestinal illness. Five hundred and ninety had episodes of overseas deployment for a median duration of 6.5 (range 0.1-149) months. Eighteen (3%) of those not deployed took doxycycline compared with 171 (30%) of those deployed. The risk of acute gastroenteritis was associated with deployment itself without clear association with doxycycline. Doxycycline exposure was associated with increased onset of IBS in those deployed to developing (odds ratio [OR], 6.99; 95% confidence interval [CI], 3.19-15.31) and developed country (OR, 6.93; 95% CI, 1.40-34.39). New onset of IBD (1.5%) was associated with deployment to developed countries and with doxycycline exposure (OR, 8.75; 95% CI, 1.67-45.86)). The use of doxycycline is a risk factor for developing IBS and possibly IBD when deployed to developing and developed countries respectively. Doxycycline as a risk factor for chronic gastrointestinal illness warrants a prospective large-scale study. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  2. Doxycycline and sulfadimethoxine transfer from cross-contaminated feed to chicken tissues.

    Science.gov (United States)

    Segato, G; Benetti, C; Angeletti, R; Montesissa, C; Biancotto, G

    2011-01-01

    During feed preparation at feed mills or during feed mixing in bins at farms, the accidental contamination of feed at trace levels by veterinary drug residues, commonly known as carry-over, can accidentally but frequently occur. To evaluate the concentrations of residual antimicrobials in poultry edible tissues, due to contaminated feed, sulfadimethoxine and doxycycline were administered for 10 days to chickens in poultry feed incurred at the contamination levels frequently found during national feed monitoring programmes (1-5 mg kg(-1)). Sulfadimethoxine and doxycycline residual concentrations detected in muscle (

  3. Innovative Biomaterials Based on Collagen-Hydroxyapatite and Doxycycline for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Narcisa Mederle

    2016-01-01

    Full Text Available Bone regeneration is a serious challenge in orthopedic applications because of bone infections increase, tumor developing, and bone loss due to trauma. In this context, the aim of our study was to develop innovative biomaterials based on collagen and hydroxyapatite (25, 50, and 75% which mimic bone composition and prevent or treat infections due to doxycycline content. The biomaterials were obtained by freeze-drying in spongious forms and were characterized by water uptake capacity and microscopy. The in vitro release of doxycycline was also determined and established by non-Fickian drug transport mechanism. Among the studied biomaterials, the most suitable one to easily deliver the drug and mimic bone structure, having compact structure and lower capacity to uptake water, was the one with 75% hydroxyapatite and being cross-linked.

  4. Interplay between Three RND Efflux Pumps in Doxycycline-Selected Strains of Burkholderia thailandensis

    Science.gov (United States)

    Biot, Fabrice Vincent; Lopez, Mélanie Monique; Poyot, Thomas; Neulat-Ripoll, Fabienne; Lignon, Sabrina; Caclard, Arnaud; Thibault, François Michel; Peinnequin, Andre; Pagès, Jean-Marie; Valade, Eric

    2013-01-01

    Background Efflux systems are involved in multidrug resistance in most Gram-negative non-fermentative bacteria. We have chosen Burkholderia thailandensis to dissect the development of multidrug resistance phenotypes under antibiotic pressure. Methodology/Principal Findings We used doxycycline selection to obtain several resistant B. thailandensis variants. The minimal inhibitory concentrations of a large panel of structurally unrelated antibiotics were determined ± the efflux pump inhibitor phenylalanine-arginine ß-naphthylamide (PAßN). Membrane proteins were identified by proteomic method and the expressions of major efflux pumps in the doxycycline selected variants were compared to those of the parental strains by a quantitative RT-PCR analysis. Doxycycline selected variants showed a multidrug resistance in two major levels corresponding to the overproduction of two efflux pumps depending on its concentration: AmrAB-OprA and BpeEF-OprC. The study of two mutants, each lacking one of these pumps, indicated that a third pump, BpeAB-OprB, could substitute for the defective pump. Surprisingly, we observed antagonistic effects between PAßN and aminoglycosides or some ß-lactams. PAßN induced the overexpression of AmrAB-OprA and BpeAB-OprB pump genes, generating this unexpected effect. Conclusions/Significance These results may account for the weak activity of PAßN in some Gram-negative species. We clearly demonstrated two antagonistic effects of this molecule on bacterial cells: the blocking of antibiotic efflux and an increase in efflux pump gene expression. Thus, doxycycline is a very efficient RND efflux pump inducer and PAßN may promote the production of some efflux pumps. These results should be taken into account when considering antibiotic treatments and in future studies on efflux pump inhibitors. PMID:24386333

  5. Drug combinations against Borrelia burgdorferi persisters in vitro: eradication achieved by using daptomycin, cefoperazone and doxycycline.

    Directory of Open Access Journals (Sweden)

    Jie Feng

    Full Text Available Although most Lyme disease patients can be cured with antibiotics doxycycline or amoxicillin using 2-4 week treatment durations, some patients suffer from persistent arthritis or post-treatment Lyme disease syndrome. Why these phenomena occur is unclear, but possibilities include host responses, antigenic debris, or B. burgdorferi organisms remaining despite antibiotic therapy. In vitro, B. burgdorferi developed increasing antibiotic tolerance as morphology changed from typical spirochetal form in log phase growth to variant round body and microcolony forms in stationary phase. B. burgdorferi appeared to have higher persister frequencies than E. coli as a control as measured by SYBR Green I/propidium iodide (PI viability stain and microscope counting. To more effectively eradicate the different persister forms tolerant to doxycycline or amoxicillin, drug combinations were studied using previously identified drugs from an FDA-approved drug library with high activity against such persisters. Using a SYBR Green/PI viability assay, daptomycin-containing drug combinations were the most effective. Of studied drugs, daptomycin was the common element in the most active regimens when combined with doxycycline plus either beta-lactams (cefoperazone or carbenicillin or an energy inhibitor (clofazimine. Daptomycin plus doxycycline and cefoperazone eradicated the most resistant microcolony form of B. burgdorferi persisters and did not yield viable spirochetes upon subculturing, suggesting durable killing that was not achieved by any other two or three drug combinations. These findings may have implications for improved treatment of Lyme disease, if persistent organisms or detritus are responsible for symptoms that do not resolve with conventional therapy. Further studies are needed to validate whether such combination antimicrobial approaches are useful in animal models and human infection.

  6. Drug combinations against Borrelia burgdorferi persisters in vitro: eradication achieved by using daptomycin, cefoperazone and doxycycline.

    Science.gov (United States)

    Feng, Jie; Auwaerter, Paul G; Zhang, Ying

    2015-01-01

    Although most Lyme disease patients can be cured with antibiotics doxycycline or amoxicillin using 2-4 week treatment durations, some patients suffer from persistent arthritis or post-treatment Lyme disease syndrome. Why these phenomena occur is unclear, but possibilities include host responses, antigenic debris, or B. burgdorferi organisms remaining despite antibiotic therapy. In vitro, B. burgdorferi developed increasing antibiotic tolerance as morphology changed from typical spirochetal form in log phase growth to variant round body and microcolony forms in stationary phase. B. burgdorferi appeared to have higher persister frequencies than E. coli as a control as measured by SYBR Green I/propidium iodide (PI) viability stain and microscope counting. To more effectively eradicate the different persister forms tolerant to doxycycline or amoxicillin, drug combinations were studied using previously identified drugs from an FDA-approved drug library with high activity against such persisters. Using a SYBR Green/PI viability assay, daptomycin-containing drug combinations were the most effective. Of studied drugs, daptomycin was the common element in the most active regimens when combined with doxycycline plus either beta-lactams (cefoperazone or carbenicillin) or an energy inhibitor (clofazimine). Daptomycin plus doxycycline and cefoperazone eradicated the most resistant microcolony form of B. burgdorferi persisters and did not yield viable spirochetes upon subculturing, suggesting durable killing that was not achieved by any other two or three drug combinations. These findings may have implications for improved treatment of Lyme disease, if persistent organisms or detritus are responsible for symptoms that do not resolve with conventional therapy. Further studies are needed to validate whether such combination antimicrobial approaches are useful in animal models and human infection.

  7. Effect of addition of 2% chlorhexidine or 10% doxycycline on antimicrobial activity of biodentine

    OpenAIRE

    Vineeta Nikhil; Molly Madan; Charu Agarwal; Navleen Suri

    2014-01-01

    Aim: The purpose of this in vitro study was to determine whether the addition of 2% chlorhexidine gluconate or 10% doxycycline would enhance the antimicrobial activity of Biodentine against Staphylococcus aureus (ATCC-25923), Enterococcus faecalis (ATCC-29212), Candida albicans (ATCC-90028), and Streptococcus mutans (MTCC-497). Materials and Methods: Three wells of 4 mm diameter and 4 mm depth on each plate were prepared on the agar medium with standardized suspensions of each microorgan...

  8. Nanotechnology in ligature-induced periodontitis: protective effect of a doxycycline gel with nanoparticules.

    Science.gov (United States)

    Botelho, Marco Antonio; Martins, Jose Galberto; Ruela, Ronaldo Sousa; Queiroz, Dinalva Brito; Ruela, Wagner Sousa

    2010-01-01

    The aim of this study was to test the efficacy of a locally applied 8.5% nanostructured doxycycline (DOX) gel in preventing alveolar bone loss in experimental periodontal disease (EPD) in rats by using the tapping mode atomic force microscopy (AFM). EPD was induced in 24 Wistar rats. Animals were treated with the doxycycline gel topically, immediately after EPD induction, and 3 times a day during 11 days. Four groups (n=6) were formed as follows: Naïve group (animals not subjected to EPD nor treated); non-treated (NT) group (animals subjected to EPD, but not treated); vehicle gel (VG) group (animals subjected to EPD and treated with topical gel vehicle); and DOX group (test group): animals subjected to EPD and treated with the 8.5% DOX gel. In order to investigate topographical changes in histological sections, a novel simple method was used for sample preparation, by etching sections from paraffin-embedded specimens with xylol. Comparing the AFM images, several grooves were observed on the surface of the alveolar bone and other periodontal structures in the NT and VG groups, with significantly greater depths when compared to the DOX group (p<0.05). Periodontal structures were brought into high relief confirming to be a simple and cost-effective method for AFM imaging with ultrastructural resolution. The doxycycline gel was able to afford periodontal surface preservation, with flatter grooves.

  9. Doxycycline plus ivermectin versus ivermectin alone for treatment of patients with onchocerciasis.

    Science.gov (United States)

    Abegunde, Ayokunle T; Ahuja, Richard M; Okafor, Nkem J

    2016-01-15

    Onchocerciasis, also known as "river blindness," is a parasitic disease that is caused by infection from the filarial nematode (roundworm), Onchocerca volvulus. Nematodes are transmitted from person to person by blackflies of the Simulium genus, which usually breed in fast flowing streams and rivers. The disease is the second leading infectious cause of blindness in endemic areas.Ivermectin (a microfilaricide) is widely distributed to endemic populations for prevention and treatment of onchocerciasis. Doxycycline, an antibiotic, targets Wolbachia organisms that are crucial to the survival of adult onchocerca (macrofilaricide). Combined treatment with both drugs is believed to cause direct microfilarial death by ivermectin and indirect macrofilarial death by doxycycline. Long-term reduction in the numbers of microfilaria in the skin and eyes and in the numbers of adult worms in the body has the potential to reduce the transmission and occurrence of onchocercal eye disease. The primary aim of this review was to assess the effectiveness of doxycycline plus ivermectin versus ivermectin alone for prevention and treatment of onchocerciasis. The secondary aim was to assess the effectiveness of doxycycline plus ivermectin versus ivermectin alone for prevention and treatment of onchocercal ocular lesions in communities co-endemic for onchocerciasis and Loa loa (loiasis) infection. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 7, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2015), EMBASE (January 1980 to July 2015), PubMed (1948 to July 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to July 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 1 July 2014), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical

  10. Nanotechnology in ligature-induced periodontitis: protective effect of a doxycycline gel with nanoparticules

    Directory of Open Access Journals (Sweden)

    Marco Antonio Botelho

    2010-08-01

    Full Text Available OBJECTIVES: The aim of this study was to test the efficacy of a locally applied 8.5% nanostructured doxycycline (DOX gel in preventing alveolar bone loss in experimental periodontal disease (EPD in rats by using the tapping mode atomic force microscopy (AFM. MATERIAL AND METHODS: EPD was induced in 24 Wistar rats. Animals were treated with the doxycycline gel topically, immediately after EPD induction, and 3 times a day during 11 days. Four groups (n=6 were formed as follows: Naïve group (animals not subjected to EPD nor treated; non-treated (NT group (animals subjected to EPD, but not treated; vehicle gel (VG group (animals subjected to EPD and treated with topical gel vehicle; and DOX group (test group: animals subjected to EPD and treated with the 8.5% DOX gel. In order to investigate topographical changes in histological sections, a novel simple method was used for sample preparation, by etching sections from paraffin-embedded specimens with xylol. RESULTS: Comparing the AFM images, several grooves were observed on the surface of the alveolar bone and other periodontal structures in the NT and VG groups, with significantly greater depths when compared to the DOX group (p<0.05. CONCLUSIONS: Periodontal structures were brought into high relief confirming to be a simple and cost-effective method for AFM imaging with ultrastructural resolution. The doxycycline gel was able to afford periodontal surface preservation, with flatter grooves.

  11. Systemic provocation in doxycycline induced fixed drug eruption: a case report

    Directory of Open Access Journals (Sweden)

    Anik Murwaningsih Rosmarini Estri Sih Hananti Niken Indrastuti

    2014-04-01

    Full Text Available Fixed drug eruption (FDE is recurrent lesions that upon repeated uptake of causative drug, always appears at the same skin and mucosal site. Determination of causal relationship in drug allergy is very important. In this case report, cases of doxycycline-induced FDE was reported. The subject of the research was a 29-year-old male, referred by dermatologist, with history of reccurent FDE. Physical examination revealed an oval well demarcated patch hyperpigmentation. Patch test was perfomed on previous involved and uninvolved site. The result of the patch test was irrelevant. Retesting patch test gave similar result. Systemic provocation test or drug provocation test (DPT  with doxcycline were done with suspected drug under ambulatory survelance and gave positive result. In this case, the DPT succeeded to identify doxycycline as the causal agent of FDE. The work-up of a suspected drug hypersensitivity includes a detailed clinical history, physical examination, skin tests, and provocation tests. The DPT is recommended to confirm drug’s hypersensitivity reactions. Systemic provocation test is considered as the gold standard for diagnosing FDE. Keywords:   fixed drug eruption - doxycycline - causal relationship - patch test - systemic provocation test

  12. Aspirin, lysine, mifepristone and doxycycline combined can effectively and safely prevent and treat cancer metastasis: prevent seeds from gemmating on soil

    Science.gov (United States)

    Xu, Huo; Ma, Ji; Zhu, Yewei; Lu, Yusheng; Wang, Jichuang; Zhang, Ting; Li, Tao; Xie, Jingjing; Xu, Bo; Xie, Fangwei; Gao, Yu; Shao, Jingwei; Tu, Xiaohuang; Jia, Lee

    2015-01-01

    Recent scientific advances have increased our understanding of the cancer metastatic complexities and provided further impetus for new combination therapies to prevent cancer metastasis. Here, we demonstrated that a combination (HAMPT) of aspirin, lysine, mifepristone and doxycycline can effectively and safely prevent cancer metastasis. The pharmaceutically-formulated HAMPT inhibited adhesion of cancer cells to either endothelial cells or extracellular matrix via down-regulating cell adhesion molecules ICAM-1 and α4-integrin. HAMPT inhibited the cloak effect by activated platelets on cancer cells, thereby interfering adhesion and invasion of cancer cells to the underlying stroma. At the effective concentration, HAMPT induced cancer cells into dormancy with minor inhibition on cell viability. Four-day pretreatment followed by 30-day oral administration of HAMPT (33.5-134 mg/kg) to the mice inoculated with cancer cells produced significant inhibition on cancer metastasis dose-dependently without marked side effects. Fifty-day rat toxicity study with HAMPT at doses (335-1340 mg/kg) 20-fold higher than its therapeutic dose produced no significant toxicity. Interestingly, the acute toxic death could not be reached at the maximum administrable dose (5 g/kg). This proof-of-concept study provides the first conceptual evidence that cancer metastasis can be controlled by using affordable old drugs to restrain circulating tumor cells from gemmating on the metastatic soil without the need for cytotoxicity. PMID:26459390

  13. Comparing efficacy of Montelukast versus doxycycline in treatment of moderate acne

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    Elham Behrangi

    2015-01-01

    Full Text Available Background: Treatment of acne is an important issue for reducing the cosmetic and psychological burden of disease. Regarding the inflammatory effect of LT-B4 in acne lesions and action mechanism of Montelukast, this study was performed to determine the efficacy of Montelukastin acne treatment comparison with doxycycline. Materials and Methods: In a randomized clinical trial that was performed in Dermatology Clinic in a Training Tertiary Health Care Center in Tehran, Iran since January 2012 to May 2014, 52 patients with moderate acne were evaluated. The included patients were randomly assigned to receive doxycycline 100 mg/day plus 1% Clindamycin solution (Group 1 or Montelukast 5 mg daily plus 1% clindamycin solution (Group 2. The acne severity index was measured and compared between two groups at baseline (on admission, 1-month and 3 months later. Independent-Sample-T, Chi-Square, and Repeated-Measure ANOVA tests were used and were considered statistically significant at P < 0.05. Results: The mean age was 26.8 ± 7.1 in Group 1 and25 ± 4.8 in Group 2 (P = 0.1. 73% women and 26.7% 4 men in Group 1 and 86.7% women, and 13.3% men in Group 2 (P = 0.01. The mean acne severity index at baseline was 18.2 ± 6.1 and 19 ± 4.2 in Montelukast and doxycycline group, respectively (P = 0.679. The mean acne severity index after 1-month was 10.5 ± 6.2 and 12.9 ± 3.3 in Montelukast and doxycycline group, respectively (P = 0. Finally, the mean acne severity index after 3 months follow-up was 8.6 ± 4.8 and 8.2 ± 1.2 in Montelukast and doxycycline group, respectively (P = 0.01. There was no significant difference between two groups regarding the amount of decrease in acne severity index across the study (P = 0.186. However, each groups showed a significant reduction in the acne severity index, separately (P = 0.001. Conclusion : It may be concluded that Montelukast is an effective and safe medication for moderate-level acne treatment.

  14. Determination of the Mutant Selection Window and Evaluation of the Killing of Mycoplasma gallisepticum by Danofloxacin, Doxycycline, Tilmicosin, Tylvalosin and Valnemulin

    National Research Council Canada - National Science Library

    Zhang, Nan; Ye, Xiaomei; Wu, Yuzhi; Huang, Zilong; Gu, Xiaoyan; Cai, Qinren; Shen, Xiangguang; Jiang, Hongxia; Ding, Huanzhong

    2017-01-01

    .... Mutant selection window (MSW) determination was used to investigate the propensity for future resistance induction by danofloxacin, doxycycline, tilmicosin, tylvalosin and valnemulin. Killing of M...

  15. Doxycycline attenuates breast cancer related inflammation by decreasing plasma lysophosphatidate concentrations and inhibiting NF-κB activation.

    Science.gov (United States)

    Tang, Xiaoyun; Wang, Xianyan; Zhao, Yuan Y; Curtis, Jonathan M; Brindley, David N

    2017-02-08

    We previously discovered that tetracyclines increase the expression of lipid phosphate phosphatases at the surface of cells. These enzymes degrade circulating lysophosphatidate and therefore doxycycline increases the turnover of plasma lysophosphatidate and decreases its concentration. Extracellular lysophosphatidate signals through six G protein-coupled receptors and it is a potent promoter of tumor growth, metastasis and chemo-resistance. These effects depend partly on the stimulation of inflammation that lysophosphatidate produces. In this work, we used a syngeneic orthotopic mouse model of breast cancer to determine the impact of doxycycline on circulating lysophosphatidate concentrations and tumor growth. Cytokine/chemokine concentrations in tumor tissue and plasma were measured by multiplexing laser bead technology. Leukocyte infiltration in tumors was analyzed by immunohistochemistry. The expression of IL-6 in breast cancer cell lines was determined by RT-PCR. Cell growth was measured in Matrigel™ 3D culture. The effects of doxycycline on NF-κB-dependent signaling were analyzed by Western blotting. Doxycycline decreased plasma lysophosphatidate concentrations, delayed tumor growth and decreased the concentrations of several cytokines/chemokines (IL-1β, IL-6, IL-9, CCL2, CCL11, CXCL1, CXCL2, CXCL9, G-CSF, LIF, VEGF) in the tumor. These results were compatible with the effects of doxycycline in decreasing the numbers of F4/80+ macrophages and CD31+ blood vessel endothelial cells in the tumor. Doxycycline also decreased the lysophosphatidate-induced growth of breast cancer cells in three-dimensional culture. Lysophosphatidate-induced Ki-67 expression was inhibited by doxycycline. NF-κB activity in HEK293 cells transiently expressing a NF-κB-luciferase reporter vectors was also inhibited by doxycycline. Treatment of breast cancer cells with doxycycline also decreased the translocation of NF-κB to the nucleus and the mRNA levels for IL-6 in the presence or

  16. Oral Doxycycline Reduces the Total Number of Intraocular Bevacizumab Injections Needed to Control Neovascular Age-related Macular Degeneration.

    Science.gov (United States)

    Mirshahi, Ahmad; Azimi, Pourya; Abdolahi, Ali; Mirshahi, Romina; Abdollahian, Mahnaz

    2017-01-01

    Tetracyclines, especially doxycycline, play a role in the regulation of inflammation, immunomodulation, cell proliferation, and angiogenesis. Treatment of corneal angiogenesis or choroidal neovascularization with tetracyclines has been shown to be effective in animal models. The aim of this study was to evaluate the efficacy of oral doxycycline in reducing the total number of intraocular injections needed for controlling neovascular age-related macular degeneration in human patients. In this interventional case series, 28 random consecutive patients with neovascular age-related macular degeneration from Farabi Eye Hospital, Tehran, Iran were treated for 4 months with 200 mg doxycycline once a day after the first intravitreal bevacizumab injection in addition to standard therapy in agreement with as-needed regimen. After 12 months of follow-up, total number of injections, foveal thickness and visual acuity were compared to those at baseline and of similar studies. Similar to standard treatment, co-treatment with doxycycline was able to control active disease (intraretinal or subretinal fluid or leakage, new-onset of macular hemorrhage, and reduction of visual acuity more than 5 letters based on Early Treatment Diabetic Retinopathy Study [ETDRS] charts) yet with fewer injections (for current study and standard treatment, respectively 3.14 vs. 5.92, P 0.05). If confirmed in larger studies, the findings of this interventional case series could provide a strategy to control neovascular age-related macular degeneration with fewer intraocular bevacizumab injections by co-administering a well-known oral agent-doxycycline.

  17. A study on the protective role of doxycycline upon dopaminergic neuron of LPS-PD rat model rat.

    Science.gov (United States)

    Zhang, G-B; Feng, Y-H; Wang, P-Q; Song, J-H; Wang, P; Wang, S-A

    2015-09-01

    To investigate the protective role of doxycycline upon the dopaminergic neuron of the lipopolysaccharide-Parkinson disease (LPS-PD) model rat and its mechanism. Animals were randomly divided into three groups: normal control group, LPS group and doxycycline intervention. Group; establishing The PD model was created by injecting LPS stereo-tactically into the substantia nigra; observing the changes in the dopaminergic neurons and the major histocompatibility complex II (MHC II) positive microglia before and after the intervention of doxycycline with immunohistochemical staining. Using the HPLC-ED (high performance liquid chromatography-electrochemical detector) to test the changes in the striatal dopamine (DA), and DOPAC (dihydroxy phenyl acetic acid) content; adopting Western blotting was adopted to test the expression of the substantia nigra microglia MHC II (major histocompatibility complex II) protein. After the intervention of doxycycline, in the LPS group, the surviving dopamine neurons in the substantia nigra rose from 38% ± 5% to 79% ± 4% (p Doxycycline can inhibit degeneration of LPS-induced dopaminergic neurons. Its neuroprotective function is achieved by downregulating the microglia MHC II expression.

  18. Doxycycline-mediated effects on persistent symptoms and systemic cytokine responses post-neuroborreliosis: a randomized, prospective, cross-over study

    Science.gov (United States)

    2012-01-01

    Background Persistent symptoms after treatment of neuroborreliosis (NB) are well-documented, although the causative mechanisms are mainly unknown. The effect of repeated antibiotic treatment has not been studied in detail. The aim of this study was to determine whether: (1) persistent symptoms improve with doxycycline treatment; (2) doxycycline has an influence on systemic cytokine responses, and; (3) improvement of symptoms could be due to doxycycline-mediated immunomodulation. Methods/Design 15 NB patients with persistent symptoms ≥6 months post-treatment were double-blindly randomized to receive 200 mg of doxycycline or a placebo for three weeks. After a six-week wash-out period, a cross-over with a three-week course of a placebo or doxycycline was conducted. The primary outcome measures were improvement of persistent symptoms assessed by neurological examinations, a symptom severity score and estimation of the quality of life. The secondary outcome measure was changes in systemic cytokine responses. Results All 15 patients finished the study. No doxycycline-mediated improvement of post-treatment symptoms or quality of life was observed. Nor could any doxycycline-mediated changes in systemic cytokine responses be detected. The study was completed without any serious adverse events. Discussion No doxycycline-mediated improvement of post-treatment symptoms or quality of life was observed. Nor could any doxycycline-mediated changes in systemic cytokine responses be detected. The study was completed without any serious adverse events. To conclude, in this pilot study, doxycycline-treatment did not lead to any improvement of either the persistent symptoms or quality of life in post-NB patients. Accordingly, doxycycline does not seem to be the optimal treatment of diverse persistent symptoms post-NB. However, the results need to be confirmed in larger studies. Trial registration NCT01205464 (clinicaltrials.gov) PMID:22876748

  19. Doxycycline-mediated effects on persistent symptoms and systemic cytokine responses post-neuroborreliosis: a randomized, prospective, cross-over study

    Directory of Open Access Journals (Sweden)

    Sjöwall Johanna

    2012-08-01

    Full Text Available Abstract Background Persistent symptoms after treatment of neuroborreliosis (NB are well-documented, although the causative mechanisms are mainly unknown. The effect of repeated antibiotic treatment has not been studied in detail. The aim of this study was to determine whether: (1 persistent symptoms improve with doxycycline treatment; (2 doxycycline has an influence on systemic cytokine responses, and; (3 improvement of symptoms could be due to doxycycline-mediated immunomodulation. Methods/Design 15 NB patients with persistent symptoms ≥6 months post-treatment were double-blindly randomized to receive 200 mg of doxycycline or a placebo for three weeks. After a six-week wash-out period, a cross-over with a three-week course of a placebo or doxycycline was conducted. The primary outcome measures were improvement of persistent symptoms assessed by neurological examinations, a symptom severity score and estimation of the quality of life. The secondary outcome measure was changes in systemic cytokine responses. Results All 15 patients finished the study. No doxycycline-mediated improvement of post-treatment symptoms or quality of life was observed. Nor could any doxycycline-mediated changes in systemic cytokine responses be detected. The study was completed without any serious adverse events. Discussion No doxycycline-mediated improvement of post-treatment symptoms or quality of life was observed. Nor could any doxycycline-mediated changes in systemic cytokine responses be detected. The study was completed without any serious adverse events. To conclude, in this pilot study, doxycycline-treatment did not lead to any improvement of either the persistent symptoms or quality of life in post-NB patients. Accordingly, doxycycline does not seem to be the optimal treatment of diverse persistent symptoms post-NB. However, the results need to be confirmed in larger studies. Trial registration NCT01205464 (clinicaltrials.gov

  20. Speciation and persistence of doxycycline in the aquatic environment: Characterization in terms of steady state kinetics.

    Science.gov (United States)

    Zaranyika, Mark F; Dzomba, Pamhidzai; Kugara, Jameson

    2015-01-01

    The aim of the present work was to establish the kinetics for the degradation of doxycycline in the aquatic environment with a view to arriving at a kinetic model that can be used to predict the persistence of antibiotic with confidence. The degradation of doxycycline in both water and sediment phases of aquatic microcosm experiments, as well as in distilled water control experiments, was studied over a period of 90 days. An initial 21% loss due to adsorption by the sediment was observed in the microcosm experiment soon after charging. Biphasic zero-order linear rates of degradation, attributed to microbial degradation of the free and sediment or colloidal particle-adsorbed antibiotic, were observed for both water phase (2.3 × 10(-2) and 4.5 × 10(-3) μgg(-1) day(-1)) and sediment phase (7.9 × 10(-3) and 1.5 × 10(-3) μgg(-1) day(-1)) of the microcosm experiment. The covered distilled water control experiment exhibited a monophasic zero-order linear rate (1.9 × 10(-3) μgg(-1) day(-1)) attributed to hydrolysis, while the distilled water experiment exposed to natural light exhibited biphasic liner rates attributed to a combination of hydrolysis and photolysis (2.9 × 10(-3) μgg(-1) day(-1)) and to microbial degradation (9.8 × 10(-3) μgg(-1) day(-1)). A kinetic model that takes into account hydrolysis, photolysis, microbial degradation as well as sorption/desorption by colloidal and sediment particles is presented to account for the observed zero-order kinetics. The implications of the observed kinetics on the persistence of doxycycline in the aquatic environment are discussed.

  1. Preventive effect of doxycycline sponge against bisphosphonate-related osteonecrosis of the jaws: an animal study

    Directory of Open Access Journals (Sweden)

    Gonca Duygu Çapar

    2016-07-01

    Full Text Available The aim of this study is to investigate the effect of doxycycline collagen sponge on bisphosphonate-related osteonecrosis of the jaw (BRONJ and the level of serum biomarkers as an indicator of osteonecrosis. Twenty-four rats were divided into four groups. Animals in the control group were injected with saline and animals in Groups I, II and III were injected with zoledronate three times a week for eight weeks. After eight weeks, the following procedures were performed in each group. In Group I: extraction of maxillary first molar, in Group II: extraction of maxillary first molar and mucoperiosteal coverage was performed and in Group III: extraction of maxillary first molar and mucoperiosteal coverage with doxycycline collagen sponges was performed. At the end of 16 weeks, all animals were sacrificed. Serum collagen type I C-telopeptide (CTx, tartrate-resistant acid phosphatase (TRACP 5b and alkaline phosphatase (ALP levels’ analysis, clinical examination, histological and histomorphometrical analysis were performed. As a result no significant difference in CTx, TRACP 5b and ALP levels was observed between groups. Complete mucosal healing was observed in all animals in the control group and 66.7% of animals in Group III. The necrotic bone area in Group III was significantly lower than the other groups (p < 0.01. Statistically significant difference was observed between groups in terms of detached osteoclast number (p < 0.01. In conclusion, local application of doxycycline could have a positive effect in reducing the risk of BRONJ in rats.

  2. Combination therapy of Avonex and doxycycline in patients with multiple sclerosis

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    Naser Sharafaddinzadeh

    2011-01-01

    Full Text Available Background: Multiple sclerosis is an inflammatory, chronic demyelinating disease of the central nervous system (CNS with unknown etiology. Multiple sclerosis causes disability in young people. An Immunomodulatory drug like Avonex (IFN β1a is used to prevent relapses or disease progression. The aim of this study is to evaluate efficacy of combination therapy (Avonex and doxycycline with standard therapy (Avonex in remitting-relapsing multiple sclerosis (RRMS.Materials and Method: A double blind clinical trial was conducted. During four-month study period, 46 patients with RRMS, under standard medication (Avonex, were entered into the study. Their EDSS score were between 1-5. They randomly allocated in to two study groups with 23cases in each arm (cases and controls. All cases were allocated to each group based on blocking method. They received Avonex only in control group and Avonex and doxycycline in case group. EDSS was measured in both groups in the beginning and at the end of study. First EDSS and EDSS scores at the end of first, second, third and fourth months in both groups were compared. Number and rate of clinical attacks and side effects of treatment were assessed in both groups. Results: In case group, there was significant changes between the first EDSS and final EDSS score, but there was not any statistically significant finding in control group after 4 months. There was no significant difference between case and control group in EDSS scores during four-month study period and there was not significant difference between case and control groups in clinical attacks. Combination therapy was well tolerated without additive side effects. Conclusion: It seems that combination of both Avonex and doxycycline in RRMS patients were effective, safe, and well tolerated

  3. Effects of minocycline and doxycycline on cell survival and gene expression in human gingival and periodontal ligament cells.

    Science.gov (United States)

    Suzuki, Ayako; Yagisawa, Junko; Kumakura, Shin-ichi; Tsutsui, Takeki

    2006-04-01

    Periodontitis is an infectious disease in the gingival crevice caused by periodontopathic bacteria, including Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans, and Tennerella forsythensis, and antibacterial agents are directly administered to the site of infection to treat it. To maximize the therapeutic effects while reducing the adverse effects, the antibacterial agents should be administered at concentrations greater than their MIC(90) doses required to inhibit the growth of 90% of periodontopathic bacteria and the administration should not damage the periodontal tissue. One approach for estimating cellular damage in the periodontal tissue caused by the administration is to assay cytological damages following exposures of cultured human cells derived from periodontal tissues to antibacterial agents. In the present study, we investigated the cytotoxic effect of minocycline (MINO) and doxycycline (DOX) by using a human gingival fibroblast cell line, a human gingival epithelial cell line, and a human periodontal ligament fibroblast cell line. We also used these cell lines to study the effect of MINO or DOX on the mRNA and protein expressions of genes associated with the differentiation of fibroblasts and the proliferation, differentiation, or cellular adhesion important to the epithelial regeneration of the periodontal attachment. The cytotoxic effect of MINO or DOX was measured as a decrease in cell survivals. The effects of these antibiotics on the mRNA and protein expressions in the cell lines were studied by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses, respectively. The maximum concentration of MINO or DOX that has little effect on the cell survivals and the mRNA and protein expressions of genes for alkaline phosphatase, type I procollagen, keratinocyte growth factor receptor, keratin 18 or 8/18, integrin beta1, integrin beta4, and laminin 5gamma2 was 10 or 30 microm, respectively

  4. Antimicrobial synergy between carprofen and doxycycline against methicill-inresistant Staphylococcus pseudintermedius ST71

    DEFF Research Database (Denmark)

    Brochmann, Rikke Prejh; Helmfrid, Linn Alexandra; Jana, Bimal

    2016-01-01

    to restore antimicrobial susceptibility in methicillin-resistant Staphylococcus pseudintermedius (MRSP). Results: A total of 216 antimicrobial/non-antimicrobial drug combinations were screened by disk diffusion using a clinical MRSP sequence type (ST) 71 strain resistant to all six antimicrobials tested...... by checkerboard assay revealed a synergistic antimicrobial effect between carprofen and doxycycline, with the sum of the fractional inhibitory concentration indexes (Sigma FICI) ranging between 0.3 and 0.5 depending on drug concentration. Checkerboard testing of multiple MRSP strains revealed a clear association...

  5. Osteogenic activity of cyclodextrin-encapsulated doxycycline in a calcium phosphate PCL and PLGA composite

    Energy Technology Data Exchange (ETDEWEB)

    Trajano, V.C.C.; Costa, K.J.R. [Restorative Dentistry Department, Faculty of Dentistry, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, CEP: 31270-901 Belo Horizonte, Minas Gerais (Brazil); Lanza, C.R.M. [Department of Oral Clinical, Surgery and Pathology, Faculty of Dentistry, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, CEP: 31270-901 Belo Horizonte, Minas Gerais (Brazil); Sinisterra, R.D. [Chemistry Department, ICEX, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, CEP: 31270-901 Belo Horizonte, Minas Gerais (Brazil); Cortés, M.E., E-mail: mecortes@ufmg.br [Restorative Dentistry Department, Faculty of Dentistry, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, CEP: 31270-901 Belo Horizonte, Minas Gerais (Brazil)

    2016-07-01

    Composites of biodegradable polymers and calcium phosphate are bioactive and flexible, and have been proposed for use in tissue engineering and bone regeneration. When associated with the broad-spectrum antibiotic doxycycline (DOX), they could favor antimicrobial action and enhance the action of osteogenic composites. Composites of polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), and a bioceramic of biphasic calcium phosphate Osteosynt® (BCP) were loaded with DOX encapsulated in β-cyclodextrin (βCD) and were evaluated for effects on osteoblastic cell cultures. The DOX/βCD composite was prepared with a double mixing method. Osteoblast viability was assessed with methyl tetrazolium (MTT) assays after 1 day, 7 day, and 14 days of composite exposure; alkaline phosphatase (AP) activity and collagen production were evaluated after 7 days and 14 days, and mineral nodule formation after 14 days. Composite structures were evaluated by scanning electron microscopy (SEM). Osteoblasts exposed to the composite containing 25 μg/mL DOX/βCD had increased cell proliferation (p < 0.05) compared to control osteoblast cultures at all experimental time points, reaching a maximum in the second week. AP activity and collagen secretion levels were also elevated in osteoblasts exposed to the DOX/βCD composite (p < 0.05 vs. controls) and reached a maximum after 14 days. These results were corroborated by Von Kossa test results, which showed strong formation of mineralization nodules during the same time period. SEM of the composite material revealed a surface topography with pore sizes suitable for growing osteoblasts. Together, these results suggest that osteoblasts are viable, proliferative, and osteogenic in the presence of a DOX/βCD-containing BCP ceramic composite. - Highlights: • Doxycycline encapsulated in β-cyclodextrin was incorpored into a polycaprolactone - poly(lactic-co-glycolic acid) - calcium phosphate • Composite’s scaffold carrying doxycycline

  6. Empyema Secondary to Actinomyces meyeri Treated Successfully with Ceftriaxone Followed by Doxycycline

    Directory of Open Access Journals (Sweden)

    Etienne Paris

    2016-01-01

    Full Text Available Actinomycosis is a relatively rare infection caused by Gram-positive bacteria. We present the case of a 54-year-old, previously healthy, male patient with a history of severe penicillin allergy who developed severe pneumonia and empyema caused by Actinomyces meyeri. Presenting symptoms included productive cough, right upper quadrant pain, and chills and rigors. He required drainage of the empyema via tube and prolonged antibiotic treatment with intravenous ceftriaxone for 2 weeks followed by oral doxycycline for 6 months.

  7. Pharmacokinetics and adverse effects of doxycycline in the treatment of Ehrlichiosis: theoretical foundations for clinical trials in canines

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    Santiago Monsalve B

    2017-05-01

    Full Text Available Ehrlichia canis is the causative bacterium of canine monocytic ehrlichiosis (CME, a disease of global importance in veterinary and human medicine. Several studies have addressed the therapeutic efficacy of tetracycline hydrochloride and doxycycline hyclate (HD for the treatment of CME, however the results are still controversial. Doxycycline is the treatment of choice for canine monocytic ehrlichiosis (CME, a well characterized disease that can serve as a model for research in diseases of the Rickettsial order and tick-borne zoonoses. Although the pharmacokinetics and efficacy of the treatment in the acute and subclinical CME phases have been known for decades, some results also indicate that Ehrlichia canis may persist in clinically normal dogs, even after an extensive treatment regimen. The purpose of this review is to (major delve into/further investigate the pharmacokinetics and side effects of doxycycline in the treatment of canine ehrlichiosis.

  8. Lack of effect of doxycycline on disease activity and joint damage in patients with rheumatoid arthritis. A double blind, placebo controlled trial

    NARCIS (Netherlands)

    Laan, W. van der; Molenaar, E.; Ronday, K.; Verheijen, J.; Breedveld, F.; Greenwald, R.; Dijkmans, B.; Tekoppele, J.

    2001-01-01

    Objective. To investigate the effects of doxycycline on disease activity and joint destruction in patients with rheumatoid arthritis (RA). Methods. A 36 week double blind, placebo controlled crossover trial was conducted. Patients (n = 66) received 50 mg doxycycline or placebo twice a day during 12,

  9. Macrofilaricidal activity after doxycycline only treatment of Onchocerca volvulus in an area of Loa loa co-endemicity: a randomized controlled trial.

    Science.gov (United States)

    Turner, Joseph D; Tendongfor, Nicholas; Esum, Mathias; Johnston, Kelly L; Langley, R Stuart; Ford, Louise; Faragher, Brian; Specht, Sabine; Mand, Sabine; Hoerauf, Achim; Enyong, Peter; Wanji, Samuel; Taylor, Mark J

    2010-04-13

    The risk of severe adverse events following treatment of onchocerciasis with ivermectin in areas co-endemic with loiasis currently compromises the development of control programmes and the treatment of co-infected individuals. We therefore assessed whether doxycycline treatment could be used without subsequent ivermectin administration to effectively deliver sustained effects on Onchocerca volvulus microfilaridermia and adult viability. Furthermore we assessed the safety of doxycycline treatment prior to ivermectin administration in a subset of onchocerciasis individuals co-infected with low to moderate intensities of Loa loa microfilaraemia. A double-blind, randomized, field trial was conducted of 6 weeks of doxycycline (200 mg/day) alone, doxycycline in combination with ivermectin (150 microg/kg) at +4 months or placebo matching doxycycline + ivermectin at +4 months in 150 individuals infected with Onchocerca volvulus. A further 22 individuals infected with O. volvulus and low to moderate intensities of Loa loa infection were administered with a course of 6 weeks doxycycline with ivermectin at +4 months. Treatment efficacy was determined at 4, 12 and 21 months after the start of doxycycline treatment together with the frequency and severity of adverse events. One hundred and four (60.5%) participants completed all treatment allocations and follow up assessments over the 21-month trial period. At 12 months, doxycycline/ivermectin treated individuals had lower levels of microfilaridermia and higher frequency of amicrofilaridermia compared with ivermectin or doxycycline only groups. At 21 months, microfilaridermia in doxycycline/ivermectin and doxycycline only groups was significantly reduced compared to the ivermectin only group. 89% of the doxycycline/ivermectin group and 67% of the doxycycline only group were amicrofilaridermic, compared with 21% in the ivermectin only group. O. volvulus from doxycycline groups were depleted of Wolbachia and all embryonic stages

  10. Macrofilaricidal Activity after Doxycycline Only Treatment of Onchocerca volvulus in an Area of Loa loa Co-Endemicity: A Randomized Controlled Trial

    Science.gov (United States)

    Turner, Joseph D.; Tendongfor, Nicholas; Esum, Mathias; Johnston, Kelly L.; Langley, R. Stuart; Ford, Louise; Faragher, Brian; Specht, Sabine; Mand, Sabine; Hoerauf, Achim; Enyong, Peter; Wanji, Samuel; Taylor, Mark J.

    2010-01-01

    Background The risk of severe adverse events following treatment of onchocerciasis with ivermectin in areas co-endemic with loiasis currently compromises the development of control programmes and the treatment of co-infected individuals. We therefore assessed whether doxycycline treatment could be used without subsequent ivermectin administration to effectively deliver sustained effects on Onchocerca volvulus microfilaridermia and adult viability. Furthermore we assessed the safety of doxycycline treatment prior to ivermectin administration in a subset of onchocerciasis individuals co-infected with low to moderate intensities of Loa loa microfilaraemia. Methods A double-blind, randomized, field trial was conducted of 6 weeks of doxycycline (200 mg/day) alone, doxycycline in combination with ivermectin (150 µg/kg) at +4 months or placebo matching doxycycline + ivermectin at +4 months in 150 individuals infected with Onchocerca volvulus. A further 22 individuals infected with O. volvulus and low to moderate intensities of Loa loa infection were administered with a course of 6 weeks doxycycline with ivermectin at +4 months. Treatment efficacy was determined at 4, 12 and 21 months after the start of doxycycline treatment together with the frequency and severity of adverse events. Results One hundred and four (60.5%) participants completed all treatment allocations and follow up assessments over the 21-month trial period. At 12 months, doxycycline/ivermectin treated individuals had lower levels of microfilaridermia and higher frequency of amicrofilaridermia compared with ivermectin or doxycycline only groups. At 21 months, microfilaridermia in doxycycline/ivermectin and doxycycline only groups was significantly reduced compared to the ivermectin only group. 89% of the doxycycline/ivermectin group and 67% of the doxycycline only group were amicrofilaridermic, compared with 21% in the ivermectin only group. O. volvulus from doxycycline groups were depleted of Wolbachia

  11. Macrofilaricidal activity after doxycycline only treatment of Onchocerca volvulus in an area of Loa loa co-endemicity: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Joseph D Turner

    2010-04-01

    Full Text Available The risk of severe adverse events following treatment of onchocerciasis with ivermectin in areas co-endemic with loiasis currently compromises the development of control programmes and the treatment of co-infected individuals. We therefore assessed whether doxycycline treatment could be used without subsequent ivermectin administration to effectively deliver sustained effects on Onchocerca volvulus microfilaridermia and adult viability. Furthermore we assessed the safety of doxycycline treatment prior to ivermectin administration in a subset of onchocerciasis individuals co-infected with low to moderate intensities of Loa loa microfilaraemia.A double-blind, randomized, field trial was conducted of 6 weeks of doxycycline (200 mg/day alone, doxycycline in combination with ivermectin (150 microg/kg at +4 months or placebo matching doxycycline + ivermectin at +4 months in 150 individuals infected with Onchocerca volvulus. A further 22 individuals infected with O. volvulus and low to moderate intensities of Loa loa infection were administered with a course of 6 weeks doxycycline with ivermectin at +4 months. Treatment efficacy was determined at 4, 12 and 21 months after the start of doxycycline treatment together with the frequency and severity of adverse events.One hundred and four (60.5% participants completed all treatment allocations and follow up assessments over the 21-month trial period. At 12 months, doxycycline/ivermectin treated individuals had lower levels of microfilaridermia and higher frequency of amicrofilaridermia compared with ivermectin or doxycycline only groups. At 21 months, microfilaridermia in doxycycline/ivermectin and doxycycline only groups was significantly reduced compared to the ivermectin only group. 89% of the doxycycline/ivermectin group and 67% of the doxycycline only group were amicrofilaridermic, compared with 21% in the ivermectin only group. O. volvulus from doxycycline groups were depleted of Wolbachia and all

  12. Doxycycline reduces the migration of tuberous sclerosis complex-2 null cells - effects on RhoA-GTPase and focal adhesion kinase.

    Science.gov (United States)

    Ng, Ho Yin; Oliver, Brian Gregory George; Burgess, Janette Kay; Krymskaya, Vera P; Black, Judith Lee; Moir, Lyn M

    2015-11-01

    Lymphangioleiomyomatosis (LAM) is associated with dysfunction of the tuberous sclerosis complex (TSC) leading to enhanced cell proliferation and migration. This study aims to examine whether doxycycline, a tetracycline antibiotic, can inhibit the enhanced migration of TSC2-deficient cells, identify signalling pathways through which doxycycline works and to assess the effectiveness of combining doxycycline with rapamycin (mammalian target of rapamycin complex 1 inhibitor) in controlling cell migration, proliferation and wound closure. TSC2-positive and TSC2-negative mouse embryonic fibroblasts (MEF), 323-TSC2-positive and 323-TSC2-null MEF and Eker rat uterine leiomyoma (ELT3) cells were treated with doxycycline or rapamycin alone, or in combination. Migration, wound closure and proliferation were assessed using a transwell migration assay, time-lapse microscopy and manual cell counts respectively. RhoA-GTPase activity, phosphorylation of p70S6 kinase (p70S6K) and focal adhesion kinase (FAK) in TSC2-negative MEF treated with doxycycline were examined using ELISA and immunoblotting techniques. The enhanced migration of TSC2-null cells was reduced by doxycycline at concentrations as low as 20 pM, while the rate of wound closure was reduced at 2-59 μM. Doxycycline decreased RhoA-GTPase activity and phosphorylation of FAK in these cells but had no effect on the phosphorylation of p70S6K, ERK1/2 or AKT. Combining doxycycline with rapamycin significantly reduced the rate of wound closure at lower concentrations than achieved with either drug alone. This study shows that doxycycline inhibits TSC2-null cell migration. Thus doxycycline has potential as an anti-migratory agent in the treatment of diseases with TSC2 dysfunction. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  13. Insights into doxycycline adsorption onto graphene nanosheet: a combined quantum mechanics, thermodynamics, and kinetic study.

    Science.gov (United States)

    Rostamian, Rahele; Behnejad, Hassan

    2018-01-01

    Recently, pharmaceutically active compounds including antibiotics have been detected in drinking water at very low levels, mostly nanogram/liter concentrations, proposing that these materials were unaffected by water treatment processes. Adsorption processes were suggested to play a significant role in the removal of antibiotics. In this study, the adsorption behavior of doxycycline (DC) in aqueous solution was evaluated. The four factors influencing the adsorption of DC onto graphene nanosheet (GNS) were studied. The results showed that initial pH ∼ 6 to 7 and contact time ∼ 200 min are optimum. The monolayer adsorption capacity was reduced with the increasing temperature from 25 to 45 °C. Nonlinear regressions were carried out to define the best fit model for every system. Among various models, the Hill isotherm model represented the equilibrium adsorption data of antibiotics while the kinetic data were well fitted by the Elovich kinetic model. The maximum adsorption capacity (q max ) was 110 mg.g -1 , obtained from the Hill equation. Semiempirical molecular orbital theory was used to investigate the molecular interaction of the adsorption system. The experiments and semiempirical computation have systematically demonstrated that DC could be adsorbed onto GNS by π- π and electrostatic interactions. It was shown that there is a good compromise with the experimental results. Graphical abstract Insights into doxycycline adsorption onto graphene nanosheet: quantum mechanics, thermodynamics, and kinetic study.

  14. Prolonged anti-bacterial activity of ion-complexed doxycycline for the treatment of osteomyelitis.

    Science.gov (United States)

    Oh, Se Heang; Nam, Bo Ra; Lee, In Soo; Lee, Jin Ho

    2016-01-01

    The main purposes of the present study are the fabrication of an ion-complexed antibiotic which allows for the continuous release of the drug for sufficient periods of time without any additional matrix leading to unfavorable tissue responses, and the feasibility study of the ion-complexed antibiotic as a therapeutic system for osteomyelitis using an animal model. An ion-complexed doxycycline (icDX) as an antibiotic was prepared by simple mixing of positively charged doxycycline hyclate (DX) and negatively charged multivalent Na2HPO4 (2Na(+) HPO4(2-)) aqueous solutions. The icDX showed a controlled release of the DX up to 6 weeks. From the in vivo feasibility study using an osteomyelitis rat model, the icDX group showed a more effective therapeutic effect for the osteomyelitis, at 3 and 6 weeks, compared to the non-treated control and free DX groups. This was due to the sustained release of DX from the icDX in the osteomyelitis bone (medullary cavity) without migration. These findings suggest that the icDX may be a promising local delivery system in the clinical field for the treatment of the osteomyelitis. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Application of advanced oxidation processes to doxycycline and norfloxacin removal from water.

    Science.gov (United States)

    Rivas, Javier; Encinas, Angel; Beltrán, Fernando; Graham, Nigel

    2011-01-01

    Doxycycline (Dxy) and Norfloxacin (Nfx) have been oxidized by means of different technologies of increasing complexity. Preliminary experiments showed that activated carbon adsorption (1.0 g L⁻¹) of these antibiotics (C(Antibiotic) = 5 × 10⁻⁵ M) led to a 60 and 85 % of total organic carbon (TOC) removal, however, a significant decrease in adsorption capacity was experienced after several reuses of the adsorbent. UV-C irradiation of Dxy (20 % removal in 2 h) or Nfx (90 % removal in 2 h) did not affect the initial TOC content of the solution while single ozonation (C(O₃) gas inlet concentration = 15.0 ppm) led to the instantaneous disappearance of the parent compounds while TOC conversion values in the proximity of 40 % were obtained. Complex systems based on the combination of ozone, UV-C radiation, titanium dioxide and activated carbon led to similar TOC removals of the order of 70 and 65 % for Dxy and Nfx, respectively. An attempt has been made to calculate the quantum yield and direct ozonation rate constants for doxycycline and norfloxacin. Additionally, the best systems, i.e., the O₃ and O₃/UV-C processes, have been simulated by a pseudoempirical model by considering TOC as a surrogate parameter.

  16. Construction of Nef-positive doxycycline-dependent HIV-1 variants using bicistronic expression elements

    Energy Technology Data Exchange (ETDEWEB)

    Velden, Yme U. van der; Kleibeuker, Wendy; Harwig, Alex; Klaver, Bep; Siteur-van Rijnstra, Esther; Frankin, Esmay; Berkhout, Ben; Das, Atze T., E-mail: a.t.das@amc.uva.nl

    2016-01-15

    Conditionally replicating HIV-1 variants that can be switched on and off at will are attractive tools for HIV research. We previously developed a genetically modified HIV-1 variant that replicates exclusively when doxycycline (dox) is administered. The nef gene in this HIV-rtTA variant was replaced with the gene encoding the dox-dependent rtTA transcriptional activator. Because loss of Nef expression compromises virus replication in primary cells and precludes studies on Nef function, we tested different approaches to restore Nef production in HIV-rtTA. Strategies that involved translation via an EMCV or synthetic internal ribosome entry site (IRES) failed because these elements were incompatible with efficient virus replication. Fusion protein approaches with the FMDV 2A peptide and human ubiquitin were successful and resulted in genetically-stable Nef-expressing HIV-rtTA strains that replicate more efficiently in primary T-cells and human immune system (HIS) mice than Nef-deficient variants, thus confirming the positive effect of Nef on in vivo virus replication. - Highlights: • Different approaches to encode additional proteins in the HIV-1 genome were tested. • IRES translation elements are incompatible with efficient HIV-1 replication. • Ubiquitin and 2A fusion protein approaches allow efficient HIV-1 replication. • Doxycycline-controlled HIV-1 variants that encode all viral proteins were developed. • Nef stimulates HIV-rtTA replication in primary cells and human immune system mice.

  17. Mucoadhesive microparticles as potential carriers in inhalation delivery of doxycycline hyclate: a comparative study

    Directory of Open Access Journals (Sweden)

    Madhusmita Mishra

    2012-10-01

    Full Text Available The present work compares and evaluates the suitability of different polymer-based microparticles for inhalation delivery of doxycycline hyclate. Mucoadhesive polymers, such as sodium carboxymethyl cellulose, sodium alginate, polyvinyl alcohol, polyvinylpyrrolidone, starch, and carbopol were selected as carriers for inhalation delivery. Microparticles were prepared by spray drying and evaluated in terms of yield, moisture content, morphology, tapped density, encapsulation efficiency, in vitro mucoadhesion, thermal properties and in vitro aerosolization performance. Additionally, the cytotoxicity of the microparticles on H1299 human alveolar cell line was examined. Smooth spherical to collapsed doughnut shaped particles were formed. They exhibited tap densities of 0.202–0.502 g/cm3 and mass median aerodynamic diameter of 3.74–6.54 μm. Mucoadhesion was highest in case of carbopol-based microparticles. Drug release from these microparticles exhibited biphasic Fickian type of diffusion. Only at the highest concentration of microparticles (1 mg/mL less than 90% cell viability was seen in DX loaded sodium alginate microparticles (DXSA, 87.2%, starch microparticles (DXST, 85.1% and carbopol microparticles (DXCP, 82.7% preparations after 48 h of exposure to alveolar cells. The results clearly indicate that sodium carboxymethyl cellulose-based microparticles may serve as an ideal carrier for inhalation delivery of doxycycline hyclate.

  18. Laboratory testing on the removal of the veterinary antibiotic doxycycline during long-term liquid pig manure and digestate storage.

    Science.gov (United States)

    Widyasari-Mehta, Arum; Suwito, Hanna Resti Kartika Ayu; Kreuzig, Robert

    2016-04-01

    The veterinary antibiotic doxycycline (DOXY) is today frequently applied in conventional pig husbandry for the control of respiratory diseases. After the treatment, pigs excrete major amounts of DOXY as the unchanged active substance. Thus, DOXY residues were found in liquid manures and digestates of biogas plants at concentrations of mg kg(-1) dry weight. In order to assess the impact of field applications of contaminated manures and digestates on the entry of DOXY residues into arable and grassland soils, thorough information about the removal of DOXY during long-term storage of farm fertilizers is required. Since this aspect has been only less investigated for manures but not for digestates, first long-term storage simulation tests were performed at laboratory scale. Within the 170-d incubation periods under strictly anaerobic conditions, doxycycline was removed in liquid pig manure by 61% and in digestate by 76%. The calculated half-lives of 120 d and 91 d thus emphasized the persistence of doxycycline in both matrices. Due to the substance specific properties of DOXY, this removal was caused neither by mineralization, epimerization nor biotransformation. According to the high affinity of DOXY to manure and digestate solids, however, the formation of non-extractable residues has to be taken into account as the predominant concentration determining process. This was indicated by the sequential extraction procedure applied. Hence, these results confirmed that a full removal capacity for doxycycline cannot be reached through the long-term storage of farm fertilizers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. A novel flow injection spectrophotometric method using plant extracts as green reagent for the determination of doxycycline

    Science.gov (United States)

    Palamy, Sysay; Ruengsitagoon, Wirat

    2017-01-01

    A novel flow injection spectrophotometric method was developed for the determination of doxycycline in pharmaceutical preparations using iron(III) contained in extracts from plants. The assay was based on the complex formed between doxycycline and iron(III) characterized by an absorption maximum at 435 nm. The calibration graphs obtained over the doxycycline concentration range 5-250 μg mL- 1 gave correlation coefficients of 0.9979, 0.9987 and 0.9987 with the three green reagents prepared from Senna alata (L.) Roxb. (S. alata), Polygonum hydropiper L. (P. hydropiper) or Diplazium esculentum (Retz.) Sw. (D. esculentum), respectively. The relative standard deviations of the repeatability was < 2.00%. The percentage recoveries were in the range of 98.27-101.03%. Doxycycline contents obtained by this new method and by the reference methods reported in literature were in agreement at 95% confidence level with the paired t-test. The sample throughput was 36 h- 1 for each green reagent.

  20. Unique expression of chronic Lyme disease and Jarisch-Herxheimer reaction to doxycycline therapy in a young adult

    National Research Council Canada - National Science Library

    Haney, Chad; Nahata, Milap C

    2016-01-01

    ... mg by mouth every 12 hours, leading to atypical sequences of events deemed a Jarisch-Herxheimer reaction by a LLMD. This case highlights the unique clinical expression of chronic Lyme disease and the Jarisch-Herxheimer response to doxycycline.

  1. Doxycycline protects human intestinal cells from hypoxia/reoxygenation injury: Implications from an in-vitro hypoxia model.

    Science.gov (United States)

    Hummitzsch, Lars; Zitta, Karina; Berndt, Rouven; Kott, Matthias; Schildhauer, Christin; Parczany, Kerstin; Steinfath, Markus; Albrecht, Martin

    2017-04-15

    Intestinal ischemia/reperfusion (I/R) injury is a grave clinical emergency and associated with high morbidity and mortality rates. Based on the complex underlying mechanisms, a multimodal pharmacological approach seems necessary to prevent intestinal I/R injury. The antibiotic drug doxycycline, which exhibits a wide range of pleiotropic therapeutic properties, might be a promising candidate for also reducing I/R injury in the intestine. To investigate possible protective effects of doxycycline on intestinal I/R injury, human intestinal CaCo-2 cells were exposed to doxycycline at clinically relevant concentrations. In order to mimic I/R injury, CaCo-2 were thereafter subjected to hypoxia/reoxygenation by using our recently described two-enzyme in-vitro hypoxia model. Investigations of cell morphology, cell damage, apoptosis and hydrogen peroxide formation were performed 24h after the hypoxic insult. Hypoxia/reoxygenation injury resulted in morphological signs of cell damage, elevated LDH concentrations in the respective culture media (Pdoxycycline (5µM, 10µM, 50µM) reduced the hypoxia induced signs of cell damage and LDH release (Pdoxycycline protects human intestinal cells from hypoxia/reoxygenation injury in-vitro. Further animal and clinical studies are required to prove the protective potential of doxycycline on intestinal I/R injury under in-vivo conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. The effect of doxycycline in infertile couples with male accessory gland infection: a double blind prospective study.

    Science.gov (United States)

    Comhaire, F H; Rowe, P J; Farley, T M

    1986-04-01

    Male accessory gland infection (MAGI, epididymo-prostato-vesiculitis) with abnormal semen quality was rarely the only abnormality in infertile couples since it occurred in no more than 1.6% of 2871 couples evaluated in 7 centres during a 3-year period. Both partners of 33 infertile couples with no other demonstrable abnormality than abnormal semen and MAGI consented to participate in a double blind trial and were treated with either doxycycline, 100 mg/day for 1 month (20 couples) or placebo (13 couples). Follow-up during a total of 175 couple-months included semen analysis and the recording of pregnancy. Pregnancy occurred in 2 of the doxycycline-treated couples (10%) and in 1 of the placebo treated couples (8%), corresponding with conception rates per month of 1.9% and 1.5%, respectively. Sperm motility and, to a lesser extent, morphology showed improvement in both groups. Evidence of infection, namely increased numbers of white blood cells and positive sperm culture, disappeared in both the doxycycline-treated and placebo group. It is concluded that features of MAGI in semen may regress spontaneously and are not influenced by the doxycycline treatment. The concomitant improvement of sperm motility and morphology still does not seem to enhance the probability of conception.

  3. Modulation of Cytokine and Cytokine Receptor/Antagonist by Treatment with Doxycycline and Tetracycline in Patients with Dengue Fever

    Directory of Open Access Journals (Sweden)

    J. E. Z. Castro

    2011-01-01

    Full Text Available Dengue virus infection can lead to dengue fever (DF or dengue hemorrhagic fever (DHF. Disease severity has been linked to an increase in various cytokine levels. In this study, we evaluated the effectiveness of doxycycline and tetracycline to modulate serum levels of IL-6, IL-1B, and TNF and cytokine receptor/receptor antagonist TNF-R1 and IL-1RA in patients with DF or DHF. Hospitalized patients were randomized to receive standard supportive care or supportive care combined with doxycycline or tetracycline therapy. Serum cytokine and cytokine receptor/antagonist levels were determined at the onset of therapy and after 3 and 7 days. Cytokine and cytokine receptor/antagonist levels were substantially elevated at day 0. IL-6, IL-1β, and TNF remained at or above day 0 levels throughout the study period in untreated patients. Treatment with tetracycline or doxycycline resulted in a significant decline in cytokine levels. Similarly, IL-1RA and TNF-R1 serum concentrations were elevated at baseline and showed a moderate increase among untreated patients. Both drugs resulted in a significant rise in IL-1Ra levels by day 3 in patients. In contrast, treatment did not affect a similar result for TNF-R1. When compared to the control group, however, a significant rise post-treatment was seen upon intragroup analysis. Further analysis demonstrated that doxycycline was significantly more effective at modulating cytokine and cytokine receptor/antagonist levels than tetracycline.

  4. Co-administration of the flavanol (-)-epicatechin with doxycycline synergistically reduces infarct size in a model of ischemia reperfusion injury by inhibition of mitochondrial swelling.

    Science.gov (United States)

    Ortiz-Vilchis, Pilar; Yamazaki, Katrina Go; Rubio-Gayosso, Ivan; Ramirez-Sanchez, Israel; Calzada, Claudia; Romero-Perez, Diego; Ortiz, Alicia; Meaney, Eduardo; Taub, Pam; Villarreal, Francisco; Ceballos, Guillermo

    2014-12-05

    (-)-Epicatechin (EPI) is cardioprotective in the setting of ischemia/reperfusion (IR) injury and doxycycline (DOX) is known to preserve cardiac structure/function after myocardial infarction (MI). The main objective of this study was to examine the effects of EPI and DOX co-administration on MI size after IR injury and to determine if cardioprotection may involve the mitigation of mitochondrial swelling. For this purpose, a rat model of IR was used. Animals were subjected to a temporary 45 min occlusion of the left anterior descending coronary artery. Treatment consisted of a single or double dose of EPI (10 mg/kg) combined with DOX (5 mg/kg). The first dose was given 15 min prior to reperfusion and the second 12 h post-MI. The effects of EPI +/- DOX on mitochondrial swelling (i.e. mPTP opening) were determined using isolated mitochondria exposed to calcium overload and data examined using isobolographic analysis. To ascertain for the specificity of EPI effects on mitochondrial swelling other flavonoids were also evaluated. Single dose treatment reduced MI size by ~46% at 48 h and 44% at three weeks. Double dosing evidenced a synergistic, 82% reduction at 3 weeks. EPI plus DOX also inhibited mitochondrial swelling in a synergic manner thus, possibly accounting for the cardioprotective effects whereas limited efficacy was observed with the other flavonoids. Given the apparent lack of toxicity in humans, the combination of EPI and DOX may have clinical potential for the treatment of myocardial IR injury. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Activation of c-Jun N-terminal kinase is essential for mitochondrial membrane potential change and apoptosis induced by doxycycline in melanoma cells

    Science.gov (United States)

    Shieh, Jiunn-Min; Huang, Tur-Fu; Hung, Chi-Feng; Chou, Kuan-Hsien; Tsai, Yih-Jeng; Wu, Wen-Bin

    2010-01-01

    Background and purpose: Tetracyclines were recently found to induce tumour cell death, but the early processes involved in this cytotoxic effect remain unclear. Experimental approach: Viability of human and mouse melanoma cells was determined by MTT assay and flow cytometry. Kinase/protein/caspase activation was measured by Western blotting and mitochondrial membrane potential (ΔΨm) was analyzed by fluorescence microscopy and flow cytometry. Key results: Human and mouse melanoma cells were treated with doxycycline or minocycline but only doxycycline was cytotoxic. This cell death (apoptosis) in A2058 cells involved activation of caspase-3, -7 and -9 and contributed to inhibition, by doxycycline, of matrix metalloproteinase (MMP) activity and migration of these cells. Doxycycline induced intra-cellular reactive oxygen species (ROS) production, apoptosis signal-regulated kinase 1 (ASK1), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation at an early stage of treatment and induced mitochondrial cytochrome c release into cytosol and ΔΨm change during apoptosis. The JNK inhibitor/small interference RNA inhibited doxycycline-induced JNK activation, ΔΨm change and apoptosis, but did not affect ASK1 activation, suggesting a role of ASK1 for JNK activation in melanoma cell apoptosis. Two ROS scavengers reduced doxycycline-induced JNK and caspase activation, and apoptosis. Taken together, the results suggest the involvement of a ROS-ASK1-JNK pathway in doxycycline-induced melanoma cell apoptosis. Conclusions and implications: We have shown a promising cytotoxic effect of doxycycline on melanoma cells, have identified ROS and ASK1 as the possible initiators and have demonstrated that JNK activation is necessary for doxycycline-induced melanoma cell apoptosis. PMID:20590610

  6. Efficiency of Nanotube Surface-Treated Dental Implants Loaded with Doxycycline on Growth Reduction of Porphyromonas gingivalis.

    Science.gov (United States)

    Ferreira, Cimara Fortes; Babu, Jegdish; Hamlekhan, Azhang; Patel, Sweetu; Shokuhfar, Tolou

    The prevalence of peri-implant infection in patients with dental implants has been shown to range from 28% to 56%. A nanotube-modified implant surface can deliver antibiotics locally and suppress periodontal pathogenic bacterial growth. The aim of this study was to evaluate the deliverability of antibiotics via a nanotube-modified implant. Dental implants with a nanotube surface were fabricated and loaded with doxycycline. Afterward, each dental implant with a nanotube surface was placed into 2-mL tubes, removed from solution, and placed in a fresh solution daily for 28 days. Experimental samples from 1, 2, 4, 16, 24, and 28 days were used for this evaluation. The concentration of doxycycline was measured using spectrophotometric analysis at 273-nm absorbance. The antibacterial effect of doxycycline was evaluated by supplementing Porphyromonas gingivalis (P gingivalis) growth media with the solution collected from the dental implants at the aforementioned time intervals for a period of 48 hours under anaerobic conditions. A bacterial viability assay was used to evaluate P gingivalis growth at 550-nm absorbance. Doxycycline concentration varied from 0.33 to 1.22 μg/mL from day 1 to day 28, respectively. A bacterial viability assay showed the highest P gingivalis growth at day 1 (2 nm) and the lowest at day 4 (0.17 nm), with a gradual reduction from day 1 to day 4 of approximately 87.5%. The subsequent growth pattern was maintained and slightly increased from baseline in approximately 48.3% from day 1 to day 24. The final P gingivalis growth measured at day 28 was 29.4% less than the baseline growth. P gingivalis growth was suppressed in media supplemented with solution collected from dental implants with a nanotube surface loaded with doxycycline during a 28-day time interval.

  7. Contemporary tetracycline susceptibility testing: doxycycline MIC methods and interpretive criteria (CLSI and EUCAST) performance when testing Gram-positive pathogens.

    Science.gov (United States)

    Jones, Ronald N; Stilwell, Matthew G; Wilson, Michael L; Mendes, Rodrigo E

    2013-05-01

    International susceptibility testing breakpoint organizations and regulatory agencies have markedly differing interpretive criteria for the tetracycline class. Here we examined the magnitude of these differences for doxycycline and tetracycline hydrochloride (HCL) when tested against a collection of 13,176 Gram-positive cocci from a worldwide surveillance network (SENTRY Antimicrobial Surveillance Program, 2010). Clinical and Laboratory Standards Institute (CLSI) breakpoints are routinely higher, usually 4-fold, compared to those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST); however, CLSI recently (2013) modified Streptococcus pneumoniae breakpoints (≤ 2 μg/mL in 2012) to ≤ 0.25 and ≤ 1 μg/mL for doxycycline and tetracycline HCL, respectively. We report that these changes are a promising step toward international breakpoint harmonization, but lack a comprehensive approach needed for testing tetracyclines against all Gram-positive cocci. Generally, EUCAST breakpoint criteria showed i) lower spectrums (reduced susceptibility rates) for the tetracyclines, but highest for doxycycline versus all species examined; ii) greater test accuracy (lower predictive categorical errors), especially for tetracycline to predict doxycycline susceptibility (99.91%); and iii) zone diameter correlate breakpoints which are generally available online. Molecular tests for tet resistance genes demonstrate that tet (K) and tet (M) containing strains can occur in the susceptible population of MIC results by both CLSI and EUCAST breakpoint criteria. In summary, doxycycline continues to show greater comparative potency versus tetracycline HCL against all monitored Gram-positive species and the international harmonization of tetracycline breakpoints should be a priority, as the most recent CLSI update only addressed 1 streptococcal species and 2 tetracycline agents. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in patients with severe nonproliferative or non-high-risk proliferative diabetic retinopathy

    DEFF Research Database (Denmark)

    Scott, Ingrid U; Jackson, Gregory R; Quillen, David A

    2014-01-01

    to receive 50 mg of doxycycline monohydrate or placebo daily for 24 months. MAIN OUTCOMES AND MEASURES: Change at 24 months compared with baseline in functional factors (frequency doubling perimetry [FDP], Humphrey photopic Swedish Interactive Thresholding Algorithm 24-2 testing, contrast sensitivity, dark...... in the placebo group (-1.9 dB) and increased in the doxycycline group (+1.8 dB) (P = .02). A higher mean FDP foveal sensitivity in the doxycycline group compared with the placebo group was detected at 6 months (P = .04), and this significant difference persisted at 12 and 24 months. A difference between...

  9. Validated spectrophotometric methods for simultaneous determination of Omeprazole, Tinidazole and Doxycycline in their ternary mixture

    Science.gov (United States)

    Lotfy, Hayam M.; Hegazy, Maha A.; Mowaka, Shereen; Mohamed, Ekram Hany

    2016-01-01

    A comparative study of smart spectrophotometric techniques for the simultaneous determination of Omeprazole (OMP), Tinidazole (TIN) and Doxycycline (DOX) without prior separation steps is developed. These techniques consist of several consecutive steps utilizing zero/or ratio/or derivative spectra. The proposed techniques adopt nine simple different methods, namely direct spectrophotometry, dual wavelength, first derivative-zero crossing, amplitude factor, spectrum subtraction, ratio subtraction, derivative ratio-zero crossing, constant center, and successive derivative ratio method. The calibration graphs are linear over the concentration range of 1-20 μg/mL, 5-40 μg/mL and 2-30 μg/mL for OMP, TIN and DOX, respectively. These methods are tested by analyzing synthetic mixtures of the above drugs and successfully applied to commercial pharmaceutical preparation. The methods that are validated according to the ICH guidelines, accuracy, precision, and repeatability, were found to be within the acceptable limits.

  10. Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent.

    Science.gov (United States)

    Kirscher, Lorenz; Deán-Ben, Xosé Luis; Scadeng, Miriam; Zaremba, Angelika; Zhang, Qian; Kober, Christina; Fehm, Thomas Felix; Razansky, Daniel; Ntziachristos, Vasilis; Stritzker, Jochen; Szalay, Aladar A

    2015-01-01

    We reported earlier the diagnostic potential of a melanogenic vaccinia virus based system in magnetic resonance (MRI) and optoacoustic deep tissue imaging (MSOT). Since melanin overproduction lead to attenuated virus replication, we constructed a novel recombinant vaccinia virus strain (rVACV), GLV-1h462, which expressed the key enzyme of melanogenesis (tyrosinase) under the control of an inducible promoter-system. In this study melanin production was detected after exogenous addition of doxycycline in two different tumor xenograft mouse models. Furthermore, it was confirmed that this novel vaccinia virus strain still facilitated signal enhancement as detected by MRI and optoacoustic tomography. At the same time we demonstrated an enhanced oncolytic potential compared to the constitutively melanin synthesizing rVACV system.

  11. Effective Delivery of Doxycycline and Epidermal Growth Factor for Expedited Healing of Chronic Wounds

    Science.gov (United States)

    Kulkarni, Abhilash

    The problems and high medical costs associated with chronic wounds necessitate an economical bioactive wound dressing. A new strategy was investigated to inhibit MMP-9 proteases and to release epidermal growth factor (EGF) to enhance healing. Doxycycline (DOX) and EGF were encapsulated on polyacrylic acid modified polyurethane film (PAA-PU) using Layer-by-Layer (LbL) assembly. The number of bilayers tuned the concentration of DOX and EGF released over time with over 94% bioactivity of EGF retained over 4 days. A simple wound model in which MMP-9 proteases were added to cell culture containing fibroblast cells demonstrated that DOX inhibited the proteases providing a protective environment for the released EGF to stimulate cell migration and proliferation at a faster healing rate. In the presence of DOX, only small amounts of the highly bioactive EGF are sufficient to close the wound. Results show that this is new and promising bioactive dressing for effective wound management.

  12. A rapid and reliable determination of doxycycline hyclate by HPLC with UV detection in pharmaceutical samples

    Directory of Open Access Journals (Sweden)

    SNEZANA S. MITIC

    2008-06-01

    Full Text Available An accurate, sensitive and reproducible high performance liquid chromatographic (HPLC method for the quantification of doxycycline hyclate in pharmaceutical samples has been developed and validated. The drug and the standard were eluted from a Lichrosorb RP-8 (250 mm´4.6 mm, 10 mm particle size at 20 °C with a mobile phase consisting of methanol, acetonitrile and 0.010 M aqueous solution of oxalic acid (2:3:5, v/v/v. The flow rate was 1.25 ml min-1. A UV detector set at 350 nm was used to monitor the effluent. Each analysis required no longer than 4 min. The limits of detection and quantification were 1.15 and 3.84 μg ml-1, respectively. Recoveries for different concentrations ranged from 99.58 to 101.93 %.

  13. A doxycycline inducible, adenoviral bone morphogenetic protein-2 gene delivery system to bone.

    Science.gov (United States)

    Bara, Jennifer J; Dresing, Iska; Zeiter, Stephan; Anton, Martina; Daculsi, Guy; Eglin, David; Nehrbass, Dirk; Stadelmann, Vincent A; Betts, Duncan C; Müller, Ralph; Alini, Mauro; Stoddart, Martin J

    2016-12-13

    We report the novel use of a tuneable, non-integrating viral gene delivery system to bone that can be combined with clinically approved biomaterials in an 'off-the-shelf' manner. Specifically, a doxycycline inducible Tet-on adenoviral vector (AdTetBMP-2) in combination with mesenchymal stromal cells (MSCs), fibrin and a biphasic calcium phosphate ceramic (MBCP®) was used to repair large bone defects in nude rats. Bone morphogenetic protein-2 (BMP-2) transgene expression could be effectively tuned by modification of the doxycycline concentration. The effect of adenoviral BMP-2 gene delivery upon bone healing was investigated in vivo in 4 mm critically sized, internally fixated, femoral defects. MSCs were transduced either by direct application of AdTetBMP-2 or by pre-coating MBCP granules with the virus. Radiological assessment scores post-mortem were significantly improved upon delivery of AdTetBMP-2. In AdTetBMP-2 groups, histological analysis revealed significantly more newly formed bone at the defect site compared with controls. Newly formed bone was vascularized and fully integrated with nascent tissue and implanted biomaterial. Improvement in healing outcome was achieved using both methods of vector delivery (direct application vs. pre-coating MCBP). Adenoviral delivery of BMP-2 enhanced bone regeneration achieved by the transplantation of MSCs, fibrin and MBCP in vivo. Importantly, our in vitro and in vivo data suggest that this can be achieved with relatively low (ng/ml) levels of the growth factor. Our model and novel gene delivery system may provide a powerful standardized tool for the optimization of growth factor delivery and release for the healing of large bone defects. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. A randomised controlled trial to compare the safety, effectiveness and cost-effectiveness of doxycycline (200 mg/day) with that of oral prednisolone (0.5 mg/kg/day) for initial treatment of bullous pemphigoid: the Bullous Pemphigoid Steroids and Tetracyclines (BLISTER) trial.

    Science.gov (United States)

    Chalmers, Joanne R; Wojnarowska, Fenella; Kirtschig, Gudula; Mason, James; Childs, Margaret; Whitham, Diane; Harman, Karen; Chapman, Anna; Walton, Shernaz; Schmidt, Enno; Godec, Thomas R; Nunn, Andrew J; Williams, Hywel C

    2017-03-01

    Bullous pemphigoid (BP) is an autoimmune blistering skin disorder with increased morbidity and mortality in the elderly. To evaluate the effectiveness, safety and cost-effectiveness of a strategy of initiating BP treatment with oral doxycycline or oral prednisolone. We hypothesised that starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral prednisolone. Pragmatic multicentre two-armed parallel-group randomised controlled trial with an economic evaluation. A total of 54 dermatology secondary care centres in the UK and seven in Germany. Adults with BP [three or more blisters at two sites and positive direct and/or indirect immunofluorescence (immunoglobulin G and/or complement component 3 immunofluorescence at the dermal-epidermal junction)] and able to give informed consent. Participants were allocated using online randomisation to initial doxycycline treatment (200 mg/day) or prednisolone (0.5 mg/kg/day). Up to 30 g/week of potent topical corticosteroids was permitted for weeks 1-3. After 6 weeks, clinicians could switch treatments or alter the prednisolone dose as per normal practice. Primary outcomes: (1) the proportion of participants with three or fewer blisters at 6 weeks (investigator blinded) and (2) the proportion with severe, life-threatening and fatal treatment-related events at 52 weeks. A regression model was used in the analysis adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed. Secondary outcomes included the effectiveness of blister control after 6 weeks, relapses, related adverse events and quality of life. The economic evaluation involved bivariate regression of costs and quality-adjusted life-years (QALYs) from a NHS perspective. In total, 132 patients were randomised to doxycycline and 121 to prednisolone. The mean patient age was 77.7 years and baseline severity was as follows: mild 31.6% (three

  15. Use of quartz crystal nanobalance to study the binding and stabilization of albumin and doxycycline on a thin layer of hydroxyapatite

    Science.gov (United States)

    Victor, Sunita Prem; Sharma, Chandra P.; Sreenivasan, K.

    2011-12-01

    This study reports the use of quartz crystal nanobalance (QCN) to study the adsorption of two model molecules namely albumin and doxycycline by hydroxyapatite (HA). The work focuses on the deposition of a stable coating of HA on the quartz crystal, modification of the coating using doxycycline and its subsequent effects on albumin adsorption. The uniformity and thickness of the HA coating has been studied using atomic force microscopy (AFM). The functional groups to ascertain the presence of the selected moieties have been characterized by Raman spectroscopy. The results indicate that the mass of albumin deposited on the surface of the HA coated quartz crystal functionalized with doxycycline shows a substantial increase when compared to the standard HA coated quartz crystal. The adsorbed albumin has also been found to be retained for an enhanced period of time. This surface immobilization of doxycycline and subsequent albumin adsorption seem to be a promising approach to confer biomaterials with antithrombogenic and antibacterial surfaces.

  16. Use of quartz crystal nanobalance to study the binding and stabilization of albumin and doxycycline on a thin layer of hydroxyapatite

    Energy Technology Data Exchange (ETDEWEB)

    Victor, Sunita Prem [Biosurface Technology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695012, Kerala (India); Sharma, Chandra P., E-mail: sharmacp@sctmist.ac.in [Biosurface Technology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695012, Kerala (India); Sreenivasan, K. [Biosurface Technology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695012, Kerala (India); Laboratory for Polymer Analysis, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695012, Kerala (India)

    2011-12-15

    This study reports the use of quartz crystal nanobalance (QCN) to study the adsorption of two model molecules namely albumin and doxycycline by hydroxyapatite (HA). The work focuses on the deposition of a stable coating of HA on the quartz crystal, modification of the coating using doxycycline and its subsequent effects on albumin adsorption. The uniformity and thickness of the HA coating has been studied using atomic force microscopy (AFM). The functional groups to ascertain the presence of the selected moieties have been characterized by Raman spectroscopy. The results indicate that the mass of albumin deposited on the surface of the HA coated quartz crystal functionalized with doxycycline shows a substantial increase when compared to the standard HA coated quartz crystal. The adsorbed albumin has also been found to be retained for an enhanced period of time. This surface immobilization of doxycycline and subsequent albumin adsorption seem to be a promising approach to confer biomaterials with antithrombogenic and antibacterial surfaces.

  17. Poor man medical pneumoplasty: Bronchoscopic lung volume reduction with hot saline versus dissolved doxycycline as a neoteric remedy of pulmonary emphysema

    Directory of Open Access Journals (Sweden)

    A.M. Abumossalam

    2016-01-01

    Conclusion: Bronchoscopic lung volume reduction by hot saline and dissolved doxycycline comes into sight to be a safe and feasible profile with an acceptable outcome that presents an attractive substitute to COPD patients who are physiologically friable.

  18. Mechanistic investigation of doxycycline photosensitization by picosecond-pulsed and continuous wave laser irradiation of cells in culture

    Energy Technology Data Exchange (ETDEWEB)

    Shea, C.R.; Hefetz, Y.; Gillies, R.; Wimberly, J.; Dalickas, G.; Hasan, T. (Massachusetts General Hospital, Boston (USA))

    1990-04-15

    In order to elucidate the photophysical mechanisms of cellular phototoxicity sensitized by doxycycline, MGH-U1 human bladder carcinoma cells in vitro were treated with 20.7 microM doxycycline and irradiated with either a pulsed (lambda = 355 nm, pulse duration = 24 ps) or a continuous wave (lambda = 351 nm) laser. Cumulative radiant exposure and irradiance were systematically varied in experiments with both lasers. Phototoxicity was assessed by epifluorescence microscopy of unfixed cells using rhodamine 123 labeling of mitochondria. With the continuous wave source, the cumulative radiant exposure required for induction of phototoxic injury was independent of irradiance. With the 24-ps-pulsed source, a significantly lower cumulative radiant exposure was required to induce the phototoxicity when the peak irradiance was 5.8 x 10(7) or 1.3 x 10(8) watts cm-2 compared with when peak irradiance was either lower (6.0 x 10(6) watts cm-2) or higher (7.6 x 10(8) watts cm-2). The measured fluorescence lifetimes of doxycycline in buffered saline solution were longer than the laser pulse duration of 24 ps. The increased efficiency of photosensitization at the optimal peak irradiance in the ps domain appears to result from sequential multiphoton absorption involving higher excited states of the singlet manifold. At the highest irradiance studied, on the other hand, reduced efficiency of photosensitization is attributed to increased photodegradation of doxycycline from higher excited states by processes such as photoionization. A model consistent with these observations is presented along with calculations, based on simple rate equations, that fit the essentials of the proposed model.

  19. Omeprazole versus doxycycline combination therapy with topical erythromycin the treatment of acne vulgaris: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Fariba Jaffary

    2017-04-01

    Full Text Available Background: Acne vulgaris is self-limiting, multifactorial disease involving sebaceous glands. Omeprazole is a proton pump inhibitor with in vitro antibacterial effects against staphylococcus aureus and anti-androgen that can be potential treatment of acne vulgaris. This study was designed to evaluate the efficacy of oral omeprazole and erythromycin 4% compared to doxycycline combination therapy in the treatment of acne vulgaris. Methods: In this clinical trial study, patients with moderate acne were referred to Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Science, Iran, during August 2014 until November 2015 and were randomized into two groups receiving topical erythromycin 4% plus omeprazole (34 patients or doxycycline (35 patients for 3 months. Moderate acne, lack of sensitivity to proton pump inhibitors, lack of warfarin, phenytoin, diazepam consumption, lack of active liver or kidney disease, being older than 12 years, were considered as inclusion criteria. Pregnant or lactating patients, patients with drug allergy history, patients taking oral contraceptives, acne topical medications (including retinoids or systemic treatment within 30 days of study, patients with oligomenorrhea, hirsutism, acne conglobata, acne fulminant or body acne alone were excluded from the study. All patients were tested for Helicobacter pylori test at the beginning of the study. Results: Both inflammatory and non-inflammatory lesions decreased in both groups with negative correlation with age (P< 0.05. There was no significant correlation between positive Helicobacter pylori test and inflammatory or non-inflammatory lesion reduction (P= 0.794, P= 0.514. Also, patient satisfaction and rate of total drug side effects was not different between two treatment groups. Rate of skin reactions was 20.58% in omeprazole treated group and 11.42% in doxycycline group. For side effects, other than skin it was 2.94% versus 14.28% respectively

  20. Comparative evaluation of inhibitory effect of curcumin and doxycycline on matrix metalloproteinase-9 activity in chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Sanjeela Rakshith Guru

    2017-01-01

    Full Text Available Background and Objectives: The pathogenesis of inflammatory periodontal diseases essentially involves degradation of extracellular matrix molecules, and collagen breakdown and matrix metalloproteinases (MMPs are proteinases primarily involved in this process. It is known that doxycycline downregulates MMP activity. Curcumin has anti-inflammatory effect and also downregulates MMP activity. Thus, a study was conducted to evaluate the anti-inflammatory effect of curcumin by its inhibition of MMP-9 activity and compare the same with doxcycline, which has known anticollagenase activity. Subjects and Methods: Gingival tissue samples were obtained from thirty patients diagnosed with chronic periodontitis. The tissue extracts were treated with Curcumin and doxycycline and inhibition of MMP-9 analyzed by gelatinzymography. Gels obtained were stained with Coomassie Brilliant Blue, and enzymatic activities detected as bands of gelatinlysis against blue background. Relative MMP-9 levels were measured by scanning the clear zones and analyzing the percentage inhibition. Results: Results showed that MMP-9 activity was significantly decreased by both the drugs. Curcumin showed 61.01% reduction in the MMP-9 activity at 1500 μg/ml concentration and doxycycline showed 59.58% reduction in the MMP-9 activity at 300 μg/ml concentration. Conclusion: The current study showed that curcumin has inhibitory effect on polymorphonuclear leukocyte-type MMP-9 involved in matrix degradation in periodontitis. Since Curcumin has a potent anti-inflammatory effect, it may have therapeutic potential as a host modulation agent in periodontal diseases.

  1. Randomized Open Trial of Gentamicin and Doxycycline for Eradication of Bartonella quintana from Blood in Patients with Chronic Bacteremia

    Science.gov (United States)

    Foucault, C.; Raoult, D.; Brouqui, P.

    2003-01-01

    Chronic Bartonella quintana bacteremia is known to occur in homeless people exposed to lice. We present here the results of an open randomized trial performed to evaluate the efficacy of doxycycline in combination with gentamicin in the eradication of B. quintana bacteremia. From 1 January 2001 to 1 April 2002, homeless people with blood cultures positive for B. quintana were randomized to receive either no treatment (untreated controls) or a combination of gentamicin (3 mg/kg of body weight/day intravenously for 14 days) and doxycycline (200 mg/day orally for 28 days). Patients were evaluated from the results of blood cultures performed between day 28 (the end of treatment) and day 90 postinclusion. Intention-to-treat analysis of 20 included patients showed eradication of bacteremia in 7 out of 9 treated patients versus 2 out of 11 untreated controls (P = 0.01). In the per-protocol analysis, eradication was obtained for 7 out of 7 treated patients versus 2 out of 9 untreated controls (P = 0.003). This study demonstrates the efficiency of the combination of doxycycline and gentamicin in eradicating B. quintana bacteremia. PMID:12821469

  2. Comparative evaluation of inhibitory effect of curcumin and doxycycline on matrix metalloproteinase-9 activity in chronic periodontitis.

    Science.gov (United States)

    Guru, Sanjeela Rakshith; Kothiwale, Shaila V; Saroch, Nitin; Guru, Rakshith Chander

    2017-01-01

    The pathogenesis of inflammatory periodontal diseases essentially involves degradation of extracellular matrix molecules, and collagen breakdown and matrix metalloproteinases (MMPs) are proteinases primarily involved in this process. It is known that doxycycline downregulates MMP activity. Curcumin has anti-inflammatory effect and also downregulates MMP activity. Thus, a study was conducted to evaluate the anti-inflammatory effect of curcumin by its inhibition of MMP-9 activity and compare the same with doxcycline, which has known anticollagenase activity. Gingival tissue samples were obtained from thirty patients diagnosed with chronic periodontitis. The tissue extracts were treated with Curcumin and doxycycline and inhibition of MMP-9 analyzed by gelatinzymography. Gels obtained were stained with Coomassie Brilliant Blue, and enzymatic activities detected as bands of gelatinlysis against blue background. Relative MMP-9 levels were measured by scanning the clear zones and analyzing the percentage inhibition. Results showed that MMP-9 activity was significantly decreased by both the drugs. Curcumin showed 61.01% reduction in the MMP-9 activity at 1500 μg/ml concentration and doxycycline showed 59.58% reduction in the MMP-9 activity at 300 μg/ml concentration. The current study showed that curcumin has inhibitory effect on polymorphonuclear leukocyte-type MMP-9 involved in matrix degradation in periodontitis. Since Curcumin has a potent anti-inflammatory effect, it may have therapeutic potential as a host modulation agent in periodontal diseases.

  3. Low efficacy of levofloxacin-doxycycline-based third-line triple therapy for Helicobacter pylori eradication in Italy.

    Science.gov (United States)

    Paoluzi, Omero Alessandro; Del Vecchio Blanco, Giovanna; Visconti, Emanuela; Coppola, Manuela; Fontana, Carla; Favaro, Marco; Pallone, Francesco

    2015-06-07

    To evaluate a levofloxacin-doxycycline-based triple therapy with or without a susceptibility culture test in non-responders to Helicobacter pylori (H. pylori) eradication. A total of 142 (99 women, 43 men; mean 53.0 ± 12.7 years) non-responders to more than two H. pylori eradication therapies underwent susceptibility culture tests or were treated with a seven-day triple therapy consisting of esomeprazole, 20 mg b.i.d., levofloxacin, 500 mg b.i.d., and doxycycline, 100 mg b.i.d., randomly associated with (n = 71) or without (n = 71) Lactobacillus casei DG. H. pylori status was checked in all patients at enrollment and at least 8 wk after the end of therapy. Compliance and tolerability of regimens were also assessed. H. pylori eradication was achieved in levofloxacin was 18% and multiple resistance was 31%. Therapy was well tolerated, and side effects were generally mild, with only one patient experiencing severe effects. Third-line levofloxacin-doxycycline triple therapy had a low H. pylori eradication efficacy, though the success and tolerability of this treatment may be enhanced with probiotics.

  4. Poly(lactide-co-glycolide) encapsulated hydroxyapatite microspheres for sustained release of doxycycline

    Energy Technology Data Exchange (ETDEWEB)

    Wang Xiaoyun [School of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China); Department of Pharmacy, Shandong Drug and Food Vocational College, Science and Technology Town, Hightech Industrial Development Zone, Weihai 264210 (China); Xu Hui; Zhao Yanqiu [School of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China); Wang Shaoning, E-mail: wsn-xh@126.com [School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China); Abe, Hiroya; Naito, Makio [Joining and Welding Research Institute, Osaka University, 11-1, Mihogaoka, Ibaraki, Osaka 567-0047 (Japan); Liu Yanli [School of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China); Wang Guoqing [School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China)

    2012-03-15

    Highlights: Black-Right-Pointing-Pointer PLGA encapsulated HAP-MSs were used for the sustained delivery of Doxycycline (Doxy, a broad spectrum tetracycline antibiotic). Black-Right-Pointing-Pointer Sustained Doxy release without obvious burst was observed. Black-Right-Pointing-Pointer Mechanism of the sustained Doxy release was illustrated. Black-Right-Pointing-Pointer Sustained Doxy release character in vivo was also obtained, the plasma Doxy levels were relatively lower and steady compared to that of the un-encapsulated HAP-MSs. - Abstract: The purpose of this study was to prepare a poly(lactide-co-glycolide) (PLGA) encapsulated hydroxyapatite microspheres (HAP-MSs) as injectable depot for sustained delivery of Doxycycline (Doxy). Doxy loaded HAP-MSs (Doxy-HAP-MSs) were encapsulated with PLGA by solid-in-oil-in-water (S/O/W) emulsion-solvent evaporation technique, the effects of the PLGA used (various intrinsic viscosity and LA/GA ratio) and ratio of PLGA/HAP-MSs on the formation of Doxy-HAP-MSs and in vitro release of Doxy were studied. The results showed that sustained drug release without obvious burst was obtained by using PLGA encapsulated HAP-MSs as the carrier, also the drug release rate could be tailored by changing the ratio of PLGA/HAP-MSs, or PLGA of various intrinsic viscosities or LA/GA ratio. Lower ratio of PLGA/HAP-MSs corresponded faster Doxy release, e.g. for the microspheres of PLGA/HAP-MSs ratio of 8 and 0.25, the in vitro Doxy release percents at the end of 7days were about 23% and 76%, respectively. Higher hydrophilicity (higher ratio of GA to LA) and lower molecular weight of PLGA corresponded to higher Doxy release rates. For in vivo release study, PLGA encapsulated HAP-MSs were subcutaneously injected to the back of mice, and the results showed good correlation between the in vivo and in vitro drug release. Meanwhile, the plasma Doxy levels after subcutaneous administration of PLGA encapsulated Doxy-HAP-MSs were relatively lower and steady

  5. The use of oral antibiotics in treating acne vulgaris: a new approach.

    Science.gov (United States)

    Farrah, Georgia; Tan, Ernest

    2016-09-01

    Although acne is not an infectious disease, oral antibiotics have remained a mainstay of treatment over the last 40 years. The anti-inflammatory properties of oral antibiotics, particularly the tetracyclines, are efficacious in treating inflammatory acne lesions. Common prescribing practices in Dermatology exert significant selection pressure on bacteria, contributing to the development of antibiotic resistance. Antibiotic use for acne not only promotes resistance in Propionibacterium acnes, but also affects other host bacteria with pathogenic potential. This review will summarize the commonly used treatments for acne vulgaris, and how they should be combined as rational treatment. The indications for using oral antibiotics in acne will be highlighted. Strategies described in the literature to conserve the utility of oral antibiotics will be summarized. These include limiting the duration of antibiotic therapy, concomitant use of a topical non-antibiotic agent, use of subantimicrobial dose doxycycline, and the introduction of topical dapsone. © 2016 Wiley Periodicals, Inc.

  6. [Pathogenesis, clinical picture, and current therapy of rosacea].

    Science.gov (United States)

    Gonser, L I; Gonser, C E; Schaller, M

    2016-01-01

    Rosacea is a common chronic inflammatory disease, especially in patients with fair skin and positive family history. Typical locations are forehead, nose, cheeks and chin; the periorbital region is usually not involved. Clinical features can be very heterogeneous. Besides different subtypes (erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea), which often overlap, various special forms of rosacea exist. Up to 60% of patients with cutaneous rosacea suffer from ocular rosacea. In Germany, brimonidine, metronidazol, azelaic acid, and ivermectin are approved for topical therapy of rosacea; for systemic therapy, doxycycline at a subantimicrobial dose (40 mg/day) is the only approved substance. In case of resistance to this therapy, contraindications or side effects, various alternative therapies are available, however off-label.

  7. Tight Long-term Dynamic Doxycycline Responsive Nigrostriatal GDNF Using a Single rAAV Vector

    Science.gov (United States)

    Manfredsson, Fredric P; Burger, Corinna; Rising, Aaron C; Zuobi-Hasona, Kheir; Sullivan, Layla F; Lewin, Alfred S; Huang, Julia; Piercefield, Emily; Muzyczka, Nicholas; Mandel, Ronald J

    2009-01-01

    Glial cell line-derived neurotrophic factor (GDNF) gene transfer is being developed as a treatment for Parkinson's disease (PD). Due to the potential for side effects, external transgene regulation should enhance this strategy's safety profile. Here, we demonstrate dynamic control during long-term expression of GDNF using a recombinant adeno-associated virus (rAAV)-based bicistronic tetracycline (tet)-off construct. Nigrostriatal GDNF overexpression induces body weight alterations in rodents, enabling longitudinal in vivo tracking of GDNF expression after nigral vector delivery. Regulated GDNF expression was highly sensitive to dietary doxycycline (DOX), displaying undetectable striatal GDNF levels at serum DOX levels below those required for antimicrobial activity. However, in the absence of DOX, striatal GDNF levels exceeded levels required for efficacy in PD models. We also demonstrate the absence of a series of known GDNF-associated side effects when using direct intrastriatal vector delivery. Therefore, this single rAAV vector system meets most of the requirements for an experimental reagent for treatment of PD. PMID:19707186

  8. Efficacy assessment of local doxycycline treatment in periodontal patients using multivariate chemometric approach.

    Science.gov (United States)

    Bogdanovska, Liljana; Poceva Panovska, Ana; Nakov, Natalija; Zafirova, Marija; Popovska, Mirjana; Dimitrovska, Aneta; Petkovska, Rumenka

    2016-08-25

    The aim of our study was application of chemometric algorithms for multivariate data analysis in efficacy assessment of the local periodontal treatment with doxycycline (DOX). Treatment efficacy was evaluated by monitoring inflammatory biomarkers in gingival crevicular fluid (GCF) samples and clinical indices before and after the local treatment as well as by determination of DOX concentration in GCF after the local treatment. The experimental values from these determinations were submitted to several chemometric algorithms: principal component analysis (PCA), partial least square discriminant analysis (PLS-DA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA). The data structure and the mutual relations of the selected variables were thoroughly investigated by PCA. The PLS-DA model identified variables responsible for discrimination of classes of data, before and after DOX treatment. The OPLS-DA model compared the efficacy of the two commonly used medications in periodontal treatment, chlorhexidine (CHX) and DOX, at the same time providing insight in their mechanism of action. The obtained results indicate that application of multivariate chemometric algorithms can be used as a valuable approach for assessment of treatment efficacy. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Doxycycline hyclate-loaded bleached shellac in situ forming microparticle for intraperiodontal pocket local delivery.

    Science.gov (United States)

    Phaechamud, Thawatchai; Chanyaboonsub, Nuttapong; Setthajindalert, Orn

    2016-10-10

    Bleached shellac (BS) is a water-insoluble polyester resin made up of sesquiterpenoid acids esterified with hydroxy aliphatic acids. In this study, BS dissolved in N-methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO) and 2-pyrrolidone was used as the internal phase of oil in oil emulsion using olive oil emulsified with glyceryl monostearate (GMS) as the external phase of in situ forming microparticles (ISM). Doxycycline hyclate (DH)-loaded BS ISMs were tested for emulsion stability, viscosity, rheology, transformation into microparticles, syringeability, drug release, surface topography, in vitro degradation and antimicrobial activities against Staphylococcus aureus, Streptococcus mutans and Porphyromonas gingivalis. All emulsions exhibited pseudoplastic flow and notably low syringeability force. Slower transformation from emulsion into microparticles of ISM prepared with 2-pyrrolidone was owing to slower solvent exchange of this solvent which promoted less porous structure of obtained BS matrix microparticles. The system containing 2-pyrrolidone exhibited a higher degradability than that prepared with DMSO. Developed DH-loaded BS ISMs exhibited a sustainable drug release for 47days with Fickian diffusion and effectively inhibited P. gingivalis, S. mutans and S. aureus. Therefore a DH-loaded BS ISM using olive oil containing GMS as the external phase and 2-pyrrolidone as a solvent was a suitable formulation for periodontitis treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Ciclosporin therapy for canine generalized discoid lupus erythematosus refractory to doxycycline and niacinamide.

    Science.gov (United States)

    Banovic, Frane; Olivry, Thierry; Linder, Keith E

    2014-10-01

    Generalized discoid lupus erythematosus (DLE) is an autoimmune skin disease variant rarely reported in dogs. The antimalarial immunomodulator hydroxychloroquine has been suggested as maintenance therapy for generalized DLE in one dog, but several recurrences were noted in the 1 year follow-up of that patient. To describe the effective treatment of generalized DLE with ciclosporin in one dog. A 6-year-old, castrated male crossbred dog was presented with pruritic, well-demarcated annular to polycyclic, hyperpigmented plaques with marginal erythema on the dorsal head, neck, trunk and medial extremities; these had been nonresponsive to treatment with doxycycline and niacinamide. Investigation included complete blood count, serum chemistry profile, urinalysis, serum antinuclear antibody test, histopathological examination and direct immunofluorescence testing of skin biopsies. The presence of lymphocyte-rich interface dermatitis on histology, together with generalized chronic recurrent hyperpigmented plaques, was consistent with the diagnosis of a generalized variant of DLE. The absence of systemic signs and unremarkable laboratory tests excluded concurrent systemic lupus erythematosus. Treatment was initiated with oral dexamethasone and ciclosporin. After 1 month, dexamethasone was discontinued and oral ketoconazole was added to the therapeutic regimen. Four months later, pruritus and erythema resolved, with most skin lesions becoming impalpable. Over the last 6 months, the patient's DLE was maintained in remission with oral ciclosporin and ketoconazole in combination every 3 days. The combination of ciclosporin and ketoconazole appeared effective to induce and maintain lesion remission in this dog with generalized DLE. © 2014 ESVD and ACVD.

  11. EFFECTIVENESS OF CIPROFLOXACIN VS DOXYCYCLINE IN TREATMENT OF RHINOSCLEROMA- A CASE-CONTROL STUDY

    Directory of Open Access Journals (Sweden)

    Shashidhar Kallapa

    2017-03-01

    Full Text Available BACKGROUND Rhinoscleroma is a chronic inflammatory condition in which deforming masses of tissue distend the nasal cavity. Klebsiella rhinoscleromatis is the causative agent. Antibiotic therapy traditionally consisted of streptomycin and tetracycline. But longterm therapy results in adverse side effects and poor patient compliance, hence this study to search alternative agents. MATERIALS AND METHODS This is a prospective study of 60 cases of rhinoscleroma visiting to the Department of ENT, KIMS, for a period of two years. RESULTS After 8 weeks treatment in the atrophic and granulomatous group, 6 (60% became histopathologically negative and 4 (40% remained histopathologically positive. The treatment was continued for another 4 weeks in positive cases and at the end of 12 weeks, 8 (80% turned histopathologically negative, 2 (20% remained positive. CONCLUSION We conclude that ciprofloxacin is a very good alternative drug compared to doxycycline in the treatment of rhinoscleroma particularly in the early stages of the disease and complete cure can be achieved by early diagnosis and treatment.

  12. Titrimetric and spectrophotometric determination of doxycycline hyclate using bromate-bromide, methyl orange and indigo carmine

    Directory of Open Access Journals (Sweden)

    Pavagada Jagannathamurthy Ramesh

    2010-07-01

    Full Text Available One titrimetric and two indirect spectrophotometric methods are described for the determination of doxycycline hyclate (DCH in bulk drug and in its formulations. The methods use bromate-bromide, methyl orange and indigo carmine as reagents. In titrimetry (method A, DCH is treated with a known excess of bromate- -bromide mixture in acid medium and the residual bromine is back titrated iodometrically after the reaction between DCH and in situ bromine is ensured to be complete. In spectrophotometric methods, the excess of bromine is estimated by treating with a fixed amount of either methyl orange (method B or indigo carmine (method C and measuring the change in absorbance either at 520 or 610 nm. Titrimetric method is applicable over 1-8 mg range and the calculations are based on a 1:2 (DCH:bromate stoichiometric ratio. In spectrophotometry, the calibration graphs were found to be linear over 0.25-1.25 and 1.0-5.0 μg mL-1 for method B and C, respectively, with corresponding molar absorptivity values of 2.62×105 and 6.97×104 L mol-1 cm-1. The accuracy and precision of the assays were determined by computing the intra-day and inter-day variations at three different levels of DCH.

  13. Effect of citric acid, tetracycline, and doxycycline on instrumented periodontally involved root surfaces: A SEM study

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    Gurparkash Singh Chahal

    2014-01-01

    Full Text Available Background: A surface smear layer consisting of organic and inorganic material is formed on the root surface following mechanical instrumentation and may inhibit the formation of new connective tissue attachment to the root surface. Modification of the tooth surface by root conditioning has resulted in improved connective tissue attachment and has advanced the goal of reconstructive periodontal treatment. Aim: The aim of this study was to compare the effects of citric acid, tetracycline, and doxycycline on the instrumented periodontally involved root surfaces in vitro using a scanning electron microscope. Settings and Design: A total of 45 dentin samples obtained from 15 extracted, scaled, and root planed teeth were divided into three groups. Materials and Methods: The root conditioning agents were applied with cotton pellets using the "Passive burnishing technique" for 5 minutes. The samples were then examined by the scanning electron microscope. Statistical Analysis Used: The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, version 15.0 for Windows. For all quantitative variables means and standard deviations were calculated and compared. For more than two groups ANOVA was applied. For multiple comparisons post hoc tests with Bonferroni correction was used. Results: Upon statistical analysis the root conditioning agents used in this study were found to be effective in removing the smear layer, uncovering and widening the dentin tubules and unmasking the dentin collagen matrix. Conclusion: Tetracycline HCl was found to be the best root conditioner among the three agents used.

  14. Effect of doxycycline on transforming growth factor-beta-1-induced matrix metalloproteinase 2 expression, migration, and collagen contraction in nasal polyp-derived fibroblasts.

    Science.gov (United States)

    Shin, Jae-Min; Park, Joo-Hoo; Kang, Byungjin; Lee, Seoung-Ae; Park, Il-Ho; Lee, Heung-Man

    2016-11-01

    It is well known that doxycycline has antibacterial and anti-inflammatory effects. In this study, we aimed to investigate the effects of doxycycline on the transforming growth factor (TGF) beta 1-induced matrix metalloproteinase (MMP) 2 expression, migration, and collagen contraction, and to determine its molecular mechanism on nasal polyp-derived fibroblasts (NPDF). NPDFs were isolated from the nasal polyps of six patients. Doxycycline was used to pretreat TGF-beta-1-induced NPDFs and ex vivo organ cultures of nasal polyps. Cytotoxicity was evaluated by using a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay. Smad2/3 is one of the major transcription factors of TGF-beta signaling. The expression levels of MMP2 and Smad2/3 were measured by using Western blotting, reverse transcription-polymerase chain reaction, and immunofluorescence staining. The enzymic activity of MMP2 was analyzed by using gelatin zymography. Fibroblast migration was evaluated by using transwell migration assays. Contractile activity was measured by a collagen gel contraction assay. The expression level of MMP2 in nasal polyp tissues increased in comparison with inferior turbinate tissues. TGF-beta-1-induced NPDFs were not affected by doxycycline (0-40 μg/mL). The expression levels of MMP2 and activation of Smad2/3 in TGF-beta-1-induced NPDFs and in organ cultures of nasal polyps were significantly downregulated with doxycycline pretreatment. Doxycycline also reduced TGF-beta-1-induced fibroblast migration and collagen contraction in NPDFs. Doxycycline inhibited TGF-beta-1-induced MMP2 expression, migration, and collagen contraction via the Smad2/3 signal pathways in NPDFs.

  15. PftetQ and pfmdt copy numbers as predictive molecular markers of decreased ex vivo doxycycline susceptibility in imported Plasmodium falciparum malaria

    Science.gov (United States)

    2013-01-01

    Background The objective of this study was to evaluate the distribution of a series of independent doxycycline inhibitory concentration 50% (IC50) values to validate the trimodal distribution previously described and to validate the use of the pftetQ and pfmdt genes as molecular markers of decreased in vitro doxycycline susceptibility in Plasmodium falciparum malaria. Methods Doxycycline IC50 values, from 484 isolates obtained at the French National Reference Centre for Imported Malaria (Paris) between January 2006 and December 2010, were analysed for the first time by a Bayesian mixture modelling approach to distinguish the different in vitro phenotypic groups by their IC50 values. Quantitative real-time polymerase chain reaction was used to evaluate the pftetQ and pfmdt copy numbers of 89 African P. falciparum isolates that were randomly chosen from the phenotypic groups. Results The existence of at least three doxycycline phenotypes was demonstrated. The mean doxycycline IC50 was significantly higher in the group with a pftetQ copy number >1 compared to the group with a pftetQ copy number = 1 (33.17 μM versus 17.23 μM) and the group with a pfmdt copy number >1 (28.28 μM versus 16.11 μM). There was a significant difference between the combined low and medium doxycycline IC50 group and the high IC50 group in terms of the per cent of isolates with one or more copy numbers of the pftetQ gene (0% versus 20.69%) or pfmdt gene (8.33% versus 37.93%). In the logistic regression model, the pfmdt and pftetQ copy numbers >1 (odds ratio = 4.65 and 11.47) were independently associated with the high IC50 group. Conclusions Copy numbers of pftetQ and pfmdt are potential predictive molecular markers of decreased susceptibility to doxycycline. PMID:24225377

  16. Effects of doxycycline on haematology, blood chemistry and peripheral blood lymphocyte subsets of healthy dogs and dogs naturally infected with Ehrlichia canis.

    Science.gov (United States)

    Villaescusa, A; García-Sancho, M; Rodríguez-Franco, F; Tesouro, M Á; Sainz, Á

    2015-06-01

    Canine monocytic ehrlichiosis (CME), caused by Ehrlichia canis, is a vector-borne disease with a worldwide distribution. It has been proposed that the pathogenesis, clinical severity and outcome of disease caused by Ehrlichia spp. can be attributed to the immune response rather than to any direct rickettsial effect. Moreover, doxycycline, the antimicrobial of choice for the treatment of CME, has immunomodulatory and anti-inflammatory properties associated with blood leukocyte proliferation function, cytokine synthesis, and matrix metalloproteinase activity. In order to assess the potential effects of doxycycline, dependent and independent of its antimicrobial activity, the present study compared changes in haematology, blood chemistry and circulating lymphocyte subpopulations in 12 healthy dogs and 20 dogs with CME after doxycycline therapy. Some changes were recorded only in the CME affected dogs, probably due to the antimicrobial effect of doxycycline. However, increases in mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelet count and α2-globulins, and decreased plasma creatinine were observed in both healthy and CME affected dogs. The absolute count of B lymphocytes (CD21(+)) increased initially, but then decreased until the end of the study period in both groups. A potential effect of doxycycline unrelated to its antimicrobial activity against E. canis is suggested, taking into account the results observed both in healthy dogs and in dogs with CME. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Evaluation of drug content (potency) for compounded and FDA-approved formulations of doxycycline on receipt and after 21 days of storage.

    Science.gov (United States)

    KuKanich, Kate; KuKanich, Butch; Slead, Tanner; Warner, Matt

    2017-10-01

    OBJECTIVE To determine drug content (potency) of compounded doxycycline formulations for veterinary use and of US FDA-approved doxycycline formulations for human use content was measured in 5 samples of each tablet, chew, or capsule formulation and 5 replicates/bottle of liquid formulation on days 1 and 21 by liquid chromatography and compared with US Pharmacopeia acceptable ranges. RESULTS All FDA-approved formulations had acceptable content on days 1 and 21. On day 1, mean doxycycline content for the 3 compounded tablet formulations was 89%, 98%, and 116% (3/5, 5/5, and 1/5 samples within acceptable ranges); day 21 content range was 86% to 112% (1/5, 5/5, and 4/5 samples within acceptable ranges). Day 1 content of chews was 81%, 78%, and 98% (0/5, 0/5, and 5/5 samples within acceptable ranges), and that of compounded liquids was 50%, 52%, and 85% (no results within acceptable ranges). No chews or compounded liquid formulations met USP standards on day 21. CONCLUSIONS AND CLINICAL RELEVANCE FDA-approved doxycycline should be prescribed when possible. Whole tablets yielded the most consistent doxycycline content for compounded formulations.

  18. Development of a Doxycycline Hydrochloride-Loaded Electrospun Nanofibrous Membrane for GTR/GBR Applications

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    Lie-ni Jia

    2016-01-01

    Full Text Available A drug-loaded membrane was prepared by electrospinning Poly ε-caprolactone (PCL with doxycycline hydrochloride (DOX (15–25% w/w. Scanning electron microscopy (SEM images revealed that fibrous average diameter decreased from 247.16±57.61 nm to 194.43±43.33 nm with the drug proportion increasing from 15% to 20% w/w, while there was no significant difference between 20% and 25% groups. The polymer matrix showed good encapsulation value (58–75% for DOX, and the drug showed an amorphous manner in the polymer matrix. The agar diffusion test revealed that DOX-loaded membranes had an obvious inhibited effect on Aggregatibacter actinomycetemcomitans (Aa and Porphyromonas gingivalis (Pg, respectively. In vitro release test showed that DOX could persistently be released for a prolonged time more than 28 days, and the DOX level in the eluent steadied at 3–5 μg/mL which was all above the minimum inhibitory concentration (MIC of DOX against Aa (0.125 μg/mL and Pg (0.0625 μg/mL. Cytocompatibility, assessed in human periodontal ligament cells (hPLCs by MTT-test and the morphology of cells on the surface of DOX-loaded membranes by SEM, indicated that all of the investigated nanofibrous membranes can be used to treat periodontal disease by integrating the GTR/GBR operation and antibiotic therapy. Above all, DOX-loaded nanofibrous membranes could have a persistent inhibited effect on periodontal pathogens to provide a relatively sterile environment for tissue repair and regeneration.

  19. Construction of doxycycline-mediated BMP-2 transgene combining with APA microcapsules for bone repair.

    Science.gov (United States)

    Qian, Dongyang; Bai, Bo; Yan, Guangbin; Zhang, Shujiang; Liu, Qi; Chen, Yi; Tan, Xiaobo; Zeng, Yanjun

    2016-01-01

    The repairing of large segmental bone defects is difficult for clinical orthopedists at present. Gene therapy is regarded as a promising method for bone defects repair. The present study aimed to construct an effective and controllable Tet-On expression system for transferring hBMP-2 gene into bone marrow mesenchymal progenitor cells (BMSCs). Meanwhile, with combination of alginate-poly-L-lysine-alginate (APA) microencapsulation technology, we attempted to reduce the influence of immunologic rejection and examine the effect of the Tet-On expression system on osteogenesis of BMSCs. The adenovirus encoding hBMP-2 (ADV-hBMP2) was constructed using the means of molecular cloning. The ADV-hBMP2 and Adeno-X Tet-On virus was respectively transfected to the HEK293 for amplification and afterward BMSCs were co-infected with the virus of ADV-hBMP2 and the Adeno-X Tet-On. The expression of hBMP-2 was measured with induction by doxycycline (DOX) at different concentration by means of RT-PCR and ELISA. Combining Tet-On expression system and APA microcapsules with the use of the pulsed high-voltage electrostatic microcapsule instrument, we examined the expression level of hBMP-2 in APA microcapsules by ELISA as well as the osteogenesis by alizarin red S staining. An effective Tet-On expression system for transferring hBMP-2 gene into BMSCs was constructed successfully. Also, the expression of hBMP-2 could be regulated by concentration of DOX. The data exhibited that BMSCs in APA microcapsules maintained the capability of proliferation and differentiation. The combination of Tet-On expression system and APA microcapsules could promote the osteogenesis of BMSCs. According to the results, microencapsulated Tet-On expression system showed the effective characteristics of secreting hBMP-2 and enhancing osteogenesis, which would provide a promising way for bone repair.

  20. Doxycycline Attenuates Leptospira-Induced IL-1β by Suppressing NLRP3 Inflammasome Priming

    Science.gov (United States)

    Zhang, Wenlong; Xie, Xufeng; Wu, Dianjun; Jin, Xuemin; Liu, Runxia; Hu, Xiaoyu; Fu, Yunhe; Ding, Zhuang; Zhang, Naisheng; Cao, Yongguo

    2017-01-01

    Doxycycline (Dox), a semisynthetic antibiotic, has been reported to exert multiple immunomodulatory effects. Treatment with Dox has a satisfactory curative effect against leptospirosis. In addition to its antibacterial action, we supposed that Dox also modulated immune response in controlling leptospira infection. Using J774A.1 mouse macrophages, the effects of Dox on protein and mRNA levels of IL-1β and TNF-α were investigated after infection with live or sonicated Leptospira interrogans serovar Lai strain Lai (56601). Specifically, the level of IL-1β but not TNF-α was sharply decreased when treated with Dox in leptospira-infected macrophages. Western blot analysis showed that Dox suppressed the activation of leptospira-induced MAPK and NF-κB signaling pathways. Using NLRP3-deficient and NLRC4-deficient mice, the data showed that the expression of leptospira-induced IL-1β was mainly dependent on the presence of NLRP3 inflammasome in macrophages. Meanwhile, Dox suppressed leptospira-induced NLRP3 inflammasome priming with the upregulation of the Na/K-ATPase Pump β1 subunit. The inhibition effect of Dox on IL-1β was also conspicuous in cells with lipopolysaccharide and ATP stimulation. These results were confirmed in vivo, as peritoneal fluids of mice and organs of hamsters expressed less IL-1β after treatment of leptospiral infection with Dox. Our results indicated that Dox also modulated immune response to attenuate leptospira-induced IL-1β by suppressing p38, JNK, p65, and NLRP3 inflammasome priming. PMID:28791016

  1. Doxycycline Attenuates Leptospira-Induced IL-1β by Suppressing NLRP3 Inflammasome Priming.

    Science.gov (United States)

    Zhang, Wenlong; Xie, Xufeng; Wu, Dianjun; Jin, Xuemin; Liu, Runxia; Hu, Xiaoyu; Fu, Yunhe; Ding, Zhuang; Zhang, Naisheng; Cao, Yongguo

    2017-01-01

    Doxycycline (Dox), a semisynthetic antibiotic, has been reported to exert multiple immunomodulatory effects. Treatment with Dox has a satisfactory curative effect against leptospirosis. In addition to its antibacterial action, we supposed that Dox also modulated immune response in controlling leptospira infection. Using J774A.1 mouse macrophages, the effects of Dox on protein and mRNA levels of IL-1β and TNF-α were investigated after infection with live or sonicated Leptospira interrogans serovar Lai strain Lai (56601). Specifically, the level of IL-1β but not TNF-α was sharply decreased when treated with Dox in leptospira-infected macrophages. Western blot analysis showed that Dox suppressed the activation of leptospira-induced MAPK and NF-κB signaling pathways. Using NLRP3-deficient and NLRC4-deficient mice, the data showed that the expression of leptospira-induced IL-1β was mainly dependent on the presence of NLRP3 inflammasome in macrophages. Meanwhile, Dox suppressed leptospira-induced NLRP3 inflammasome priming with the upregulation of the Na/K-ATPase Pump β1 subunit. The inhibition effect of Dox on IL-1β was also conspicuous in cells with lipopolysaccharide and ATP stimulation. These results were confirmed in vivo , as peritoneal fluids of mice and organs of hamsters expressed less IL-1β after treatment of leptospiral infection with Dox. Our results indicated that Dox also modulated immune response to attenuate leptospira-induced IL-1β by suppressing p38, JNK, p65, and NLRP3 inflammasome priming.

  2. Doxycycline Attenuates Leptospira-Induced IL-1β by Suppressing NLRP3 Inflammasome Priming

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    Wenlong Zhang

    2017-07-01

    Full Text Available Doxycycline (Dox, a semisynthetic antibiotic, has been reported to exert multiple immunomodulatory effects. Treatment with Dox has a satisfactory curative effect against leptospirosis. In addition to its antibacterial action, we supposed that Dox also modulated immune response in controlling leptospira infection. Using J774A.1 mouse macrophages, the effects of Dox on protein and mRNA levels of IL-1β and TNF-α were investigated after infection with live or sonicated Leptospira interrogans serovar Lai strain Lai (56601. Specifically, the level of IL-1β but not TNF-α was sharply decreased when treated with Dox in leptospira-infected macrophages. Western blot analysis showed that Dox suppressed the activation of leptospira-induced MAPK and NF-κB signaling pathways. Using NLRP3-deficient and NLRC4-deficient mice, the data showed that the expression of leptospira-induced IL-1β was mainly dependent on the presence of NLRP3 inflammasome in macrophages. Meanwhile, Dox suppressed leptospira-induced NLRP3 inflammasome priming with the upregulation of the Na/K-ATPase Pump β1 subunit. The inhibition effect of Dox on IL-1β was also conspicuous in cells with lipopolysaccharide and ATP stimulation. These results were confirmed in vivo, as peritoneal fluids of mice and organs of hamsters expressed less IL-1β after treatment of leptospiral infection with Dox. Our results indicated that Dox also modulated immune response to attenuate leptospira-induced IL-1β by suppressing p38, JNK, p65, and NLRP3 inflammasome priming.

  3. A Triple and Quadruple Therapy with Doxycycline and Bismuth for First-Line Treatment of Helicobacter pylori Infection: A Pilot Study.

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    Ciccaglione, Antonio Francesco; Cellini, Luigina; Grossi, Laurino; Manzoli, Lamberto; Marzio, Leonardo

    2015-10-01

    Tetracycline-containing triple therapy has been suggested as an alternative first-line therapy for H. pylori infection. To evaluate the effect of two dosages of doxycycline (DOX) associated with amoxicillin and esomeprazole with and without bismuth subcitrate as first-line treatment of H. pylori infection. Helicobacter pylori-positive patients underwent a 10-day therapy randomized into four groups: Group A received esomeprazole, amoxicillin, and DOX-100 mg b.i.d. (EAD-100), Group B a quadruple therapy with esomeprazole, amoxicillin, DOX-100 mg b.i.d. and bismuth subcitrate (EADB-100), Group C a triple therapy with esomeprazole, amoxicillin, and DOX-200 mg b.i.d. (EAD-200) and Group D a quadruple therapy with esomeprazole, amoxicillin, DOX-200 mg b.i.d., and bismuth subcitrate (EADB-200). Success was accessed by (13)C urea breath test 2 months after the end of treatment. The number of patients to be recruited for each group had to be at least 50 subjects. Treatment success of 80% or less was considered unacceptable. Stopping rules therefore were anytime six failures had occurred. In the EAD-100 group and in EAD-200 group, the recruitment was stopped at the 14th and 15th patient, respectively. Fifty-two patients entered in the EADB-100 group and 51 in the EADB-200 group. Intention to treat eradication was in EADB-100 group 46/52 (88.5%, 95% CI 76.6-95.6); in the EADB-200 group 47/51 (92.1%, 95% CI: 81.1-97.8) (n.s.). Side effects were absent. The adjunction of bismuth subcitrate to a triple therapy that includes esomeprazole, amoxicillin, and DOX in patients who are treated for the first time for the H. pylori infection potentiates the therapeutic effect. This regimen, however, deserves to be optimized in terms of duration and dose of DOX. © 2015 John Wiley & Sons Ltd.

  4. Development of a standardized susceptibility test for Campylobacter with quality control ranges for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem

    DEFF Research Database (Denmark)

    McDermott, P. F.; Bodeis, S. M.; Aarestrup, Frank Møller

    2004-01-01

    A standardized agar dilution susceptibility testing method was developed for Campylobacter that consisted of testing on Mueller-Hinton medium supplemented with 5% defibrinated sheep blood in an atmosphere of 10% CO2, 5% O-2, and 85% N-2- Campylobacter jejuni ATCC 33560 was identified as a quality-control...... (QC) strain. Minimal inhibitory concentration (MIC) QC ranges were determined for two incubation time/temperature combinations: 36degreesC for 48 hr and 42degreesC for 24 hr. Quality-control ranges were determined for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem. For all...

  5. The effects of pharmaceutically active compound doxycycline on the corrosion of mild steel in hydrochloric acid solution

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, Sudhish Kumar [Department of Applied Chemistry, Institute of Technology, Banaras Hindu University, Varanasi 221 005, Uttar Pradesh (India); Quraishi, M.A. [Department of Applied Chemistry, Institute of Technology, Banaras Hindu University, Varanasi 221 005, Uttar Pradesh (India)], E-mail: maquraishi.apc@itbhu.ac.in

    2010-02-15

    Corrosion inhibition of mild steel in hydrochloric acid solution by doxycycline has been studied by weight loss measurements, polarization resistance, Tafel polarization and electrochemical impedance spectroscopy. The inhibitor showed more than 95% inhibition efficiency at optimum concentration 9.02 x 10{sup -4} M. Potentiodynamic polarization suggests that it is a mixed type of inhibitor. Electrochemical impedance spectroscopy was used to investigate the mechanism of corrosion inhibition. Thermodynamic parameters were calculated to investigate mechanism of inhibition. The compound follows Langmuir adsorption isotherm. AFM studies of mild steel surface with and without inhibitor were performed and calculated roughness also supported the inhibition data.

  6. Effect of doxycycline concentrations in chicken tissues as a consequence of permanent exposure to enrofloxacin traces in drinking water

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    Gbylik-Sikorska Małgorzata

    2016-09-01

    Full Text Available Introduction: The main problem in poultry farming is the difficulty in producing food of animal origin without using antibacterial agents. Because most antibacterial compounds are dispensed in water, some water supply systems can be contaminated by antibiotics which are then administered to the animals unintentionally. This can lead to unexpected increases in antibiotic residues in food of animal origin. The aim of the present study was to determine whether the constant exposure of chicken broilers to enrofloxacin affects the withdrawal time of a therapeutic doxycycline that is intentionally administered to the chickens.

  7. The development and validation of an analytical method for doxycycline quantification in human plasma - doi:10.5020/18061230.2007.p193

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    Geysa Aguiar

    2012-01-01

    Full Text Available The aim of this study was to develop and validate a simple, quick and sensitive assay for determination of doxycycline concentration in human plasma by High Performance Liquid Chromatography (HPLC. Doxycycline and Oxytetracycline (internal standard were extracted from 0,5 mL human plasma into ethyl acetate. The HPLC system was operated isocratically at controlled temperature (30°C with reversed phase Phenomenex Luna C8 column (150 mm x 4.6mm i.d.; 4 ?m particle size and using a mobile phase consisting in water: acetonitrile: tetrahydrofuran (80:15:5 v/v/v adjusted to pH 2.5, at a flow rate of 1.0 mL/min. Detection was achieved with a UV detector at 357 nm. Method validation investigated parameters such as the sensitivity, linearity (r2= 0.9946, precision, accuracy, recovery and stability. The limit of quantification was 0,25 ?g/mL. Under the assay conditions, doxycycline and oxytetracycline had retention times of 7,5 and 2,4 minutes, respectively. No interferences with endogenous compounds or with anticoagulant were observed. The mean recovery of doxycycline was 84.57%, and 80.73% for the intern standard at working concentration (20?g/mL. The method showed to be precise and accurate both for analyses held in a same day (intra-day as in different days (inter-days. A good stability of doxycycline and oxytetracycline was observed during extraction and analysis, when stored over a fourmonth period at -20°C, on the auto sample during 24 hours and to 3 freeze-thaw cycles. The present method is suitable for sensitive, precise and accurate determination of doxycycline concentrations in human plasma, within the limits established for this type of analyses

  8. Effectiveness of Long-term Doxycycline Treatment and Cognitive-Behavioral Therapy on Fatigue Severity in Patients with Q Fever Fatigue Syndrome (Qure Study): A Randomized Controlled Trial.

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    Keijmel, Stephan P; Delsing, Corine E; Bleijenberg, Gijs; van der Meer, Jos W M; Donders, Rogier T; Leclercq, Monique; Kampschreur, Linda M; van den Berg, Michel; Sprong, Tom; Nabuurs-Franssen, Marrigje H; Knoop, Hans; Bleeker-Rovers, Chantal P

    2017-04-15

    Approximately 20% of patients with acute Q fever will develop chronic fatigue, referred to as Q fever fatigue syndrome (QFS). The objective of this randomized controlled clinical trial was to assess the efficacy of either long-term treatment with doxycycline or cognitive-behavioral therapy (CBT) in reducing fatigue severity in patients with QFS. Adult patients were included who met the QFS criteria according to the Dutch guideline: a new onset of severe fatigue lasting ≥6 months with significant disabilities, related to an acute Q fever infection, without other somatic or psychiatric comorbidity explaining the fatigue. Using block randomization, patients were randomized between oral study medication and CBT (2:1) for 24 weeks. Second, a double-blind randomization between doxycycline (200 mg/day, once daily) and placebo was performed in the medication group. Primary outcome was fatigue severity at end of treatment (EOT; week 26), assessed with the Checklist Individual Strength subscale Fatigue Severity. Of 155 patients randomized, 154 were included in the intention-to-treat analysis (doxycycline, 52; placebo, 52; CBT, 50). At EOT, fatigue severity was similar between doxycycline (40.8 [95% confidence interval {CI}, 37.3-44.3]) and placebo (37.8 [95% CI, 34.3-41.2]; difference, doxycycline vs placebo, -3.0 [97.5% CI, -8.7 to 2.6]; P = .45). Fatigue severity was significantly lower after CBT (31.6 [95% CI, 28.0-35.1]) than after placebo (difference, CBT vs placebo, 6.2 [97.5% CI, .5-11.9]; P = .03). CBT is effective in reducing fatigue severity in QFS patients. Long-term treatment with doxycycline does not reduce fatigue severity in QFS patients compared to placebo. NCT01318356.

  9. Community-directed delivery of doxycycline for the treatment of onchocerciasis in areas of co-endemicity with loiasis in Cameroon

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    Wanji Samuel

    2009-08-01

    Full Text Available Abstract Background Severe side effects following ivermectin treatment of onchocerciasis in areas of co-endemicity with loaisis have been an impediment for the work of the African Programme for Onchocerciasis Control (APOC in forested regions of several countries. Doxycycline has been shown to be effective in the treatment of onchocerciasis and has the added advantages of killing adult Onchocerca volvulus but neither adult Loa loa nor their microfilariae. This drug therefore offers great potential for the treatment of onchocerciasis in areas of co-endemicity with loiasis. The limitation of use of this drug is the duration of treatment that may pose a potential problem with therapeutic coverage and compliance with treatment. To benefit from the advantages that doxycycline offers in the treatment of onchocerciasis, it will be necessary to establish an effective distribution system that can access remote communities. This study assessed the feasibility of a large-scale distribution of doxycycline for the treatment of onchocerciasis in areas of co-endemicity with loiasis using a community-directed approach. Methods The study was carried out in 5 health areas co-endemic for Onchocerca volvulus and Loa loa which had no prior experience of the Community Directed Treatment with Ivermectin (CDTI. The community-directed delivery process was introduced using a cascade mechanism from the central health system that passed through the regional health delegation, health district and the health areas. Community health implementers (CHIs were trained to deliver doxycycline to community members and, under the supervision of the health system, to monitor and document drug intake and side effects. Results The community members adhered massively to the process. Of the 21355 individuals counted, 17519 were eligible for treatment and 12936 were treated with doxycycline; giving a therapeutic coverage of eligible population of 73.8%. Of the 12936 who started the

  10. Multifunctional nanoparticles for doxycycline delivery towards localized elastic matrix stabilization and regenerative repair.

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    Sivaraman, Balakrishnan; Ramamurthi, Anand

    2013-05-01

    Abdominal aortic aneurysms (AAAs) are abnormal expansions of the aortic wall, typically characterized by chronic up-regulation of matrix metalloproteases (MMPs)-2 and -9. These MMPs degrade elastin and elastic matrix within the aortic wall, leading to a progressive loss of elasticity of the abdominal aorta as the condition progresses. Doxycycline (DOX) is a tetracycline-based antibiotic which has shown significant promise in delaying and slowing the growth of AAAs in both clinical studies and animal models. However, it has been found to inhibit elastic matrix deposition by vascular cells at dosages in the μg ml(-1) range, which is typically observed in the circulation, in addition to systemic side effects, following oral dosage. In this paper, we describe the development of DOX-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles for localized, controlled and sustained DOX delivery towards AAA therapy. Further, we demonstrate that surface functionalization of these nanoparticles with cationic amphiphiles not only imparts them with a positive charge for potentially enhanced aortic uptake, but also enables enhanced elastin binding via hydrophobic interactions, as well as up-regulating activity of the elastin crosslinking enzyme lysyl oxidase. In addition to the DOX released from the nanoparticles being effective in inhibiting MMP-2 production and activity, we also demonstrate that surface functionalization of the nanoparticles cationic amphiphiles may also play a role in MMP-2 inhibition via (i) electrostatic interactions with negatively charged residues in the active-site of MMP-2 or (ii) steric blockade of the active site on account of the presence of two dodecyl chains in the DMAB molecule. Thus, in addition to enhanced aortic uptake and retention illustrated in studies by other groups, we have demonstrated that cationic functionalization of PLGA nanoparticles enhances elastogenic outcomes by targeted binding to elastin, as well as their potential to inhibit

  11. Optimization of the doxycycline-dependent simian immunodeficiency virus through in vitro evolution

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    Piatak Mike

    2008-06-01

    Full Text Available Abstract Background Vaccination of macaques with live attenuated simian immunodeficiency virus (SIV provides significant protection against the wild-type virus. The use of a live attenuated human immunodeficiency virus (HIV as AIDS vaccine in humans is however considered unsafe because of the risk that the attenuated virus may accumulate genetic changes during persistence and evolve to a pathogenic variant. We earlier presented a conditionally live HIV-1 variant that replicates exclusively in the presence of doxycycline (dox. Replication of this vaccine strain can be limited to the time that is needed to provide full protection through transient dox administration. Since the effectiveness and safety of such a conditionally live virus vaccine should be tested in macaques, we constructed a similar dox-dependent SIV variant. The Tat-TAR transcription control mechanism in this virus was inactivated through mutation and functionally replaced by the dox-inducible Tet-On regulatory system. This SIV-rtTA variant replicated in a dox-dependent manner in T cell lines, but not as efficiently as the parental SIVmac239 strain. Since macaque studies will likely require an efficiently replicating variant, we set out to optimize SIV-rtTA through in vitro viral evolution. Results Upon long-term culturing of SIV-rtTA, additional nucleotide substitutions were observed in TAR that affect the structure of this RNA element but that do not restore Tat binding. We demonstrate that the bulge and loop mutations that we had introduced in the TAR element of SIV-rtTA to inactivate the Tat-TAR mechanism, shifted the equilibrium between two alternative conformations of TAR. The additional TAR mutations observed in the evolved variants partially or completely restored this equilibrium, which suggests that the balance between the two TAR conformations is important for efficient viral replication. Moreover, SIV-rtTA acquired mutations in the U3 promoter region. We demonstrate

  12. Efficacy of doxycycline release collagen membrane on surgically created and contaminated defects in rat tibiae: A histopathological and microbiological study.

    Science.gov (United States)

    Kütan, Esma; Duygu-Çapar, Gonca; Özçakir-Tomruk, Ceyda; Dilek, Ozkan Cem; Özen, Fatma; Erdoğan, Özge; Özdemir, Ipek; Korachi, May; Gürel, Aydin

    2016-03-01

    The effects of systemic antibiotics on controlling infective pathogens after guided bone regeneration(GBR) procedures especially in membrane exposures are limited. However, local administrations of antibiotics are rare in GBR techniques. The aim of this study was to investigate the osteogenesis potential and the antibacterial effect of a doxycycline releasing collagen membrane in surgically created and contaminated defects in rat tibiae. Defects were created in 20 rats that were randomly divided in to two groups: control group (defect contaminated by Porphyromonas gingivalis, filled with bone graft and covered by collagen membrane); test group (defect contaminated by P. gingivalis filled with bone graft and covered by collagen membrane containing 1mg/cm(2) doxycycline. Animals were sacrificed post surgically on the 14th day for microbiologic evaluation and on the 28th day for histopathological evaluation. The degree of osteogenesis in the test group was seen to be significantly higher than control group (p: 0.011; pmembrane has a positive effect on contaminated GBR procedures for limiting P. gingivalis infections leading to bone formation following GBR procedures in a rat model. Copyright © 2015. Published by Elsevier Ltd.

  13. A randomized study comparing levofloxacin, omeprazole, nitazoxanide, and doxycycline versus triple therapy for the eradication of Helicobacter pylori.

    Science.gov (United States)

    Basu, P Patrick; Rayapudi, Krishna; Pacana, Tommy; Shah, Niraj James; Krishnaswamy, Nithya; Flynn, Molly

    2011-11-01

    Resistance to standard Helicobacter pylori (HP) treatment regimens has led to unsatisfactory cure rates in HP-infected patients. This study was designed to evaluate a novel four-drug regimen (three antibiotics and a proton pump inhibitor (PPI)) for eradication of HP infection in treatment-naive patients. Patients with a diagnosis of HP gastritis or peptic ulcer disease confirmed using endoscopy and stool antigen testing were eligible for inclusion in this study. All patients underwent a washout period of 6 weeks from any prior antibiotic or PPI usage. Patients were then randomized to either levofloxacin, omeprazole, nitazoxanide, and doxycycline (LOAD) therapy for 7 days (LOAD-7) or 10 days (LOAD-10), including levofloxacin 250 mg with breakfast, omeprazole 40 mg before breakfast, nitazoxanide (Alina) 500 mg twice daily with meals and doxycycline 100 mg at dinner, or lansoprozole, amoxicillin, and clarithromycin (LAC) therapy for 10 days, which included lansoprozole 30 mg, amoxicillin 1 g with breakfast and dinner, and clarithromycin 500 mg with breakfast and dinner. HP eradication was confirmed by stool antigen testing at least 4 weeks after cessation of therapy. Intention-to-treat analysis revealed significant differences (Ptreatment of HP in treatment-naive patients. A large randomized controlled trial is warranted to further evaluate the efficacy of this regimen.

  14. The Effect of Locally Delivered Doxycycline in the Treatment of Chronic Periodontitis. A Clinical and Microbiological Cohort Study

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    Ioannis Ioannou

    2010-10-01

    Full Text Available Objectives: To evaluate the efficacy of locally delivered doxycycline as an adjunct to non-surgical treatment with the use of an ultrasonic device compared to scaling and root planing using hand instruments, by means of clinical and microbiological criteria.Material and Methods: Thirty three patients with chronic periodontitis participated in this cohort study and were divided into two groups. Patients in control group received scaling and root planing using hand instruments, whereas patients in control group received ultrasonic debridement and 8.8% doxycycline gel was applied after initial therapy and at 3 months at preselected sites. Clinical recordings concerning probing pocket depth, clinical attachment level, plaque index and gingival bleeding index were performed at baseline, 3 and 6 months after baseline. Subgingival samples were analysed using the “checkerboard” DNA-DNA hybridisation technique for Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola.Results: Both treatments resulted in significant improvement in all clinical recordings. Six months after the treatment a statistically significant decrease was observed for Porphyromonas gingivalis in both of groups and Treponema denticola in the control group (P < 0.05. No inter-group differences were observed (P < 0.05.Conclusions: Both treatment modalities provided comparable clinical and microbiological results in the treatment of chronic periodontitis.

  15. Eucaryotic cells protect Borrelia burgdorferi from the action of penicillin and ceftriaxone but not from the action of doxycycline and erythromycin.

    Science.gov (United States)

    Brouqui, P; Badiaga, S; Raoult, D

    1996-06-01

    Despite appropriate antibiotic treatment, Lyme disease patients may have relapses or may develop chronic manifestations. The intracellular location of Borrelia burgdorferi suggests that antibiotics that penetrate cells will have greater efficiency. Doxycycline or erythromycin was more effective than penicillin or ceftriaxone in killing B. burgdorferi when the organism was grown in the presence of eucaryotic cells.

  16. Matrix metalloproteinases and their tissue inhibitor after reperfused ST-elevation myocardial infarction treated with doxycycline. Insights from the TIPTOP trial.

    Science.gov (United States)

    Cerisano, Giampaolo; Buonamici, Piergiovanni; Gori, Anna Maria; Valenti, Renato; Sciagrà, Roberto; Giusti, Betti; Sereni, Alice; Raspanti, Silvia; Colonna, Paolo; Gensini, Gian Franco; Abbate, Rosanna; Schulz, Richard; Antoniucci, David

    2015-10-15

    The TIPTOP (Early Short-term Doxycycline Therapy In Patients with Acute Myocardial Infarction and Left Ventricular Dysfunction to Prevent The Ominous Progression to Adverse Remodelling) trial demonstrated that a timely, short-term therapy with doxycycline is able to reduce LV dilation, and both infarct size and severity in patients treated with primary percutaneous intervention (pPCI) for a first ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction. In this secondary, pre-defined analysis of the TIPTOP trial we evaluated the relationship between doxycycline and plasma levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). In 106 of the 110 (96%) patients enrolled in the TIPTOP trial, plasma MMPs and TIMPs were measured at baseline, and at post-STEMI days 1, 7, 30 and 180. To evaluate the remodeling process, 2D-Echo studies were performed at baseline and at 6months. A (99m)Tc-SPECT was performed to evaluate the 6-month infarct size and severity. Doxycycline therapy was independently related to higher plasma TIMP-2 levels at day 7 (pdoxycycline therapy results in higher plasma levels of TIMP-2 which, in turn, inversely correlate with 6month infarct size and severity as well as LV dilation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Development and Validation of a Stability-Indicating RP-HPLC Method for Rapid Determination of Doxycycline in Pharmaceutical Bulk and Dosage Forms

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    Shabnam Pourmoslemi, Soroush Mirfakhraee, Saeid Yaripour, Ali Mohammadi

    2016-06-01

    Full Text Available Background: A rapid stability-indicating RP-HPLC method for analysis of doxycycline in the presence of its degradation products was developed and validated. Methods: Forced degradation studies were carried out on bulk samples and capsule dosage forms of doxycycline using acid, base, H2O2, heat, and UV light as described by ICH for stress conditions to demonstrate the stability-indicating power of the method. Separations were performed on a Perfectsil® Target ODS column (3-5µm, 125 mm×4 mm, using a mobile phase consisting of methanol-50 mM ammonium acetate buffer (containing 0.1% v/v trifluoroacetic acid and 0.1% v/v triethylamine, pH 2.5 (50:50 v/v at room temperature. The flow rate was 0.8 mL/min. Results: The method linearity was investigated in the range of 25–500 µg/mL (r > 0.9999. The LOD and LOQ were 5 and 25 µg/mL, respectively. The method selectivity was evaluated by peak purity test using a diode array detector. There was no interference among detection of doxycycline and its stressed degradation products. Total peak purity numbers were in the range of 0.94-0.99, indicating the homogeneity of DOX peaks. Conclusion: These data show the stability-indicating nature of the method for quality control of doxycycline in bulk samples and capsule dosage forms.

  18. Different effect of doxycycline and enrofloxacin on ca¬thelicidin-3 mRNA expression in chickens with or without probiotics supplementati

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    I. Pavlova

    2017-12-01

    Full Text Available The function of immune system of poultry has a significant impact on poultry husbandry sustainabi¬lity. Therefore the aim of this study was to investigate the effect of lactic acid bacteria administered with enrofloxacin or doxycycline on expression levels of antimicrobial peptide cathelicidin-3 (CATH3 at mRNA level in the duodenum, jejunum and liver of broilers. A day-old Ross (n=24 and Duc (n=24 chickens were included in experiments with enrofloxacin and doxycycline, respectively. They were divided into four groups (n=6 for each experiment: control, supplemented with probiotics (15 days via feed, 5 days after hatching, treated with either enrofloxacin or doxycycline (10 mg.kg-1 for 5 days, via drinking water and treated with antibiotic and probiotics. Expression levels of CATH3 mRNA in liver, duodenum and jejunum were determined by RT-PCR and were statistically evaluated by Mann-Whitney test.Administration of probiotics led to insignificant down-regulation of CATH3 mRNA in the investigated tissues. The combination of doxycycline with probiotics led to statistically significant down-regulation of CATH3 mRNA in the duodenum (P<0.01. Statistically significant up-regulation of mRNA of the studied gene was found in the jejunum of enrofloxacin treated Ross chickens. The data suggest the existence of an interaction between antibiotics and innate immunity. Further evaluation in infected poultry would shed more light on the pharmacodynamics of antibacterials.

  19. Mid-esophageal ulceration and candidiasis-associated distal esophagitis as two distinct clinical patterns of tetracycline or doxycycline-induced esophageal injury.

    Science.gov (United States)

    Gencosmanoglu, Rasim; Kurtkaya-Yapicier, Ozlem; Tiftikci, Arzu; Avsar, Erol; Tozun, Nurdan; Oran, Ebru Sen

    2004-07-01

    Tetracyclines may cause esophageal injury. The aims of this study are to describe 2 distinct clinical patterns of esophageal injury induced by tetracycline or its derivate doxycycline and to compare these patterns with respect to demographic, endoscopic, and clinical characteristics of the patients. Forty-eight patients with the diagnosis of doxycycline- or tetracycline-induced esophageal injury by endoscopy were analyzed retrospectively. The patients were considered in 2 groups according to the type and the location of esophageal lesions (Group A: mid-esophageal ulceration, n = 18; Group B: distal esophagitis, n = 30). Patients in Group A were significantly younger than in Group B (P = 0.0014). In Group A, 15 patients (83%) had single ulceration, 2 (11%) double, and 1 (6%) circumferential at the mid-esophagus. In Group B, all patients had multiple micro-ulcerations in the distal esophagus. Development of mid-esophageal ulceration was induced predominantly by doxycycline, whereas distal esophagitis was induced by tetracycline. The description of drug ingestion with little or no water by patients in Group A was significantly more frequent than in Group B (94% vs. 10%, P esophageal candidiasis were significantly more frequent in Group B (P = 0.006, P esophageal injury because mid-esophageal ulceration seems to be more frequently associated with doxycycline and distal esophagitis with or without candidiasis with tetracycline.

  20. Doxycycline for prevention of erlotinib-induced rash in patients with non-small-cell lung cancer (NSCLC) after failure of first-line chemotherapy: A randomized, open-label trial.

    Science.gov (United States)

    Deplanque, Gaël; Gervais, Radj; Vergnenegre, Alain; Falchero, Lionel; Souquet, Pierre-Jean; Chavaillon, Jean-Michel; Taviot, Bruno; Fraboulet, Ghislaine; Saal, Hakim; Robert, Caroline; Chosidow, Olivier

    2016-06-01

    Rash is a common epidermal growth factor receptor inhibitor-induced toxicity that can impair quality of life and treatment compliance. We sought to evaluate the efficacy of doxycycline in preventing erlotinib-induced rash (folliculitis) in patients with non-small-cell lung cancer. This open-label, randomized, prospective, phase II trial was conducted in 147 patients with locally advanced or metastatic non-small-cell lung cancer progressing after first-line chemotherapy, randomized for 4 months with erlotinib alone 150 mg/d per os (control arm) or combined with doxycycline 100 mg/d (doxycycline arm). Incidence and severity of rash, compliance, survival, and safety were assessed. Baseline characteristics of the 147 patients were well balanced in the intent-to-treat population. Folliculitis occurred in 71% of patients in the doxycycline arm and 81% in the control arm (P = .175). The severity of folliculitis and other skin lesions was lower in the doxycycline arm compared with the control arm. Other adverse events were reported at a similar frequency across arms. There was no significant difference in survival between treatment arms. The open-label design of the study and the duration of the treatment with doxycycline are limitations. Doxycycline did not reduce the incidence of erlotinib-induced folliculitis, but significantly reduced its severity. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  1. Experimental Dirofilaria immitis infection in dogs: effects of doxycycline and Advantage Multi® administration on immature adult parasites.

    Science.gov (United States)

    Chandrashekar, R; Beall, M J; Saucier, J; O'Connor, T; McCall, J W; McCall, S D

    2014-11-15

    To better understand the efficacy of doxycycline and 10% imidacloprid+2.5% moxidectin (Advantage Multi(®); Bayer Animal Health, Shawnee Mission, Kansas) on immature adult Dirofilaria immitis parasites and the results of antigen tests, 12 healthy, randomly selected dogs were experimentally infected with D. immitis and monitored for 407 days. Two dogs in each of three subgroups of four dogs were each infected with six (total of 6 dogs) or 12 (total of 6 dogs) D. immitis infective third-stage larvae (L3) obtained from infected mosquitoes. Doxycycline (10mg/kg per os twice daily×30 days) and 10% imidacloprid+2.5% moxidectin (1ml/kg by topical application every 30 days) treatment was initiated at 105 (Group A) and 149 (Group B) days post infection (PI) in two groups. One subgroup of two dogs given 6 L3 and one subgroup of two dogs given 12 L3 remained as untreated controls (GroupC). Serum obtained regularly throughout the study was evaluated by ELISA (PetChek(®) Heartworm-PF Antigen Test, IDEXX Laboratories, Inc.) for D. immitis adult circulating antigens. Six of the eight dogs in the treated groups had detectable antigenemia starting between 148 and 240 days post infection, but antigen was not detected in any treated dog at the end of the study. In the control subgroups, the dogs that received 6 L3 had no detectable antigen while the two dogs that received 12 L3 had detectable antigen beginning on Day 180 that persisted until the end of the study. None of the infected dogs had evidence of circulating microfilariae. At necropsy, no heartworms were recovered from the treated dogs, but all dogs in the untreated group had viable adult heartworms. These results indicate that early immature adult worms (3.5 and 5 months of age) of D. immitis were susceptible to a combined treatment regimen of doxycycline and 10% imidacloprid+2.5% moxidectin. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Single dosage of doxycycline for prophylaxis against leptospiral infection and leptospirosis during urban flooding in southern Thailand: a non-randomized controlled trial.

    Science.gov (United States)

    Chusri, Sarunyou; McNeil, Edward B; Hortiwakul, Thanaporn; Charernmak, Boonsri; Sritrairatchai, Somporn; Santimaleeworagun, Wichai; Pattharachayakul, Sutthiporn; Suksanan, Paritasana; Thaisomboonsuk, Butsaya; Jarman, Richard G

    2014-11-01

    This study was conducted to investigate the protective efficacy of a single dosage of 200 mg doxycycline against leptospiral infection and leptospirosis and associated risk factors among residents exposed to flooding in southern Thailand. Of 641 participants, 600 received doxycycline while 41 did not. Twenty two participants were infected with Leptospira and six developed leptospirosis. Having a laceration wound was significantly associated with leptospiral infection (odds ratio [OR] = 37.20; P leptospirosis (OR = 18.24; P = 0.003) whereas exposure to flood more than 3 h per day was associated with only leptospiral infection (OR = 3.70; P = 0.038). Seventeen participants who received doxycycline and five who did not, were infected with Leptospira, resulting a protective efficacy of 76.8% (95% confidence interval [CI] = 34.3%-92.0%). Four who received doxycycline and two who did not, developed leptospirosis, resulting a protective efficacy of 86.3% (CI = -9.8%-98.2%). Among the participants with laceration wound, the protective efficacy for leptospiral infection was 92.0% (CI = 81.2%-96.6%) and for leptospirosis was 95.6% (CI = 78.2%-99.3%). Among the participants exposed to flood water less than or equal to 3 h per day, the protective efficacy for leptospiral infection was 89.2% (95% CI 63.6%-96.67%). A single dosage of 200 mg doxycycline for prophylaxis might be effective for preventing leptospirosis among flood victims with laceration wound after recent flood exposure. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. All rights reserved.

  3. Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, Justin; Holmuhamedov, Ekhson; Zhang, Xun; Lovelace, Gregory L.; Smith, Charles D. [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC (United States); Lemasters, John J., E-mail: JJLemasters@musc.edu [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC (United States); Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC (United States)

    2013-11-15

    Minocycline, a tetracycline-derived compound, mitigates damage caused by ischemia/reperfusion (I/R) injury. Here, 19 tetracycline-derived compounds were screened in comparison to minocycline for their ability to protect hepatocytes against damage from chemical hypoxia and I/R injury. Cultured rat hepatocytes were incubated with 50 μM of each tetracycline-derived compound 20 min prior to exposure to 500 μM iodoacetic acid plus 1 mM KCN (chemical hypoxia). In other experiments, hepatocytes were incubated in anoxic Krebs–Ringer–HEPES buffer at pH 6.2 for 4 h prior to reoxygenation at pH 7.4 (simulated I/R). Tetracycline-derived compounds were added 20 min prior to reperfusion. Ca{sup 2+} uptake was measured in isolated rat liver mitochondria incubated with Fluo-5N. Cell killing after 120 min of chemical hypoxia measured by propidium iodide (PI) fluorometry was 87%, which decreased to 28% and 42% with minocycline and doxycycline, respectively. After I/R, cell killing at 120 min decreased from 79% with vehicle to 43% and 49% with minocycline and doxycycline. No other tested compound decreased killing. Minocycline and doxycycline also inhibited mitochondrial Ca{sup 2+} uptake and suppressed the Ca{sup 2+}-induced mitochondrial permeability transition (MPT), the penultimate cause of cell death in reperfusion injury. Ru360, a specific inhibitor of the mitochondrial calcium uniporter (MCU), also decreased cell killing after hypoxia and I/R and blocked mitochondrial Ca{sup 2+} uptake and the MPT. Other proposed mechanisms, including mitochondrial depolarization and matrix metalloprotease inhibition, could not account for cytoprotection. Taken together, these results indicate that minocycline and doxycycline are cytoprotective by way of inhibition of MCU. - Highlights: • Minocycline and doxycycline are the only cytoprotective tetracyclines of those tested • Cytoprotective tetracyclines inhibit the MPT and mitochondrial calcium and iron uptake. • Cytoprotective

  4. Flow-injection spectrophotometric determination of tetracycline and doxycycline in pharmaceutical formulations using chloramine-T as oxidizing agent

    Directory of Open Access Journals (Sweden)

    José L. Rufino

    2009-01-01

    Full Text Available A flow-injection (FI spectrophotometric procedure is proposed for tetracycline (TC and doxycycline (DXC determination in pharmaceuticals. The method is based on the reaction of oxidation of these drugs by chloramine-T in alkaline medium producing red color products (λmax = 535 and 525 nm. Beer´s law is obeyed in the concentration range from 6.62 x 10-5 to 7.72 x 10-4 mol L-1 and 5.37 x 10-5 to 7.16 x 10-4 mol L-1 for TC and DXC, respectively. The analytical frequency was 50 h"1 and 45 h-1 for TC and DXC, respectively. The results obtained by the proposed method were in good agreement with those obtained by the official method at 95% confidence level.

  5. Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice

    Directory of Open Access Journals (Sweden)

    Zheng Liu

    2012-04-01

    Full Text Available Abstract Background Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Methods Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. Results The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. Conclusion These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy.

  6. Lyme neuroborreliosis in HIV-1 positive men successfully treated with oral doxycycline: a case series and literature review

    Directory of Open Access Journals (Sweden)

    Gisslén Magnus

    2011-09-01

    Full Text Available Abstract Introduction Lyme neuroborreliosis is the most common bacterial central nervous system infection in the temperate parts of the northern hemisphere. Even though human immunodeficiency virus (HIV -1 infection is common in Lyme borreliosis endemic areas, only five cases of co-infection have previously been published. Four of these cases presented with typical Lyme neuroborreliosis symptoms such as meningoradiculitis and facial palsy, while a fifth case had more severe symptoms of encephalomyelitis. All five were treated with intravenous cephalosporins and clinical outcome was good for all but the fifth case Case presentations We present four patients with concomitant presence of HIV-1 infection and Lyme neuroborreliosis diagnosed in Western Sweden. Patient 1 was a 60-year-old Caucasian man with radicular pain and cognitive impairment. Patient 2 was a 39-year-old Caucasian man with headaches, leg weakness, and pontine infarction. Patient 3 was a 62-year-old Caucasian man with headaches, tremor, vertigo, and normal-pressure hydrocephalus. Patient 4 was a 50-year-old Caucasian man with radicular pain and peripheral facial palsy. Patients one, two, and three all had subnormal levels of CD4 cells, indicating impaired immunity. All patients were treated with oral doxycycline with good clinical outcome and normalization of CSF pleocytosis. Conclusion Given the low HIV-1 prevalence and medium incidence of Lyme neuroborreliosis in Western Sweden where these four cases were diagnosed, co-infection with HIV-1 and Borrelia is probably more common than previously thought. The three patients that were the most immunocompromised suffered from more severe and rather atypical neurological symptoms than are usually described among patients with Lyme neuroborreliosis. It is therefore important for doctors treating HIV patients to consider Lyme neuroborreliosis in a patient presenting with atypical neurological symptoms. All four patients were treated with

  7. The effect of topical treatment with doxycycline compared to saline on 66 avulsed permanent teeth--a retrospective case-control study.

    Science.gov (United States)

    Tsilingaridis, Georgios; Malmgren, Barbro; Skutberg, Caroline; Malmgren, Olle

    2015-06-01

    Tooth avulsion in young growing individuals is an uncommon but very severe dental trauma. The aim of this retrospective case-control study was to evaluate the effect of topical treatment with doxycycline on avulsed permanent teeth compared with treatment with only saline regarding pulp survival and periodontal healing. Sixty-six avulsed teeth in 50 patients (34 boys and 16 girls) between the ages six and 18 years were included in this study. Thirty teeth were soaked in a 0.05 mg ml(-1) doxycycline solution for 5 min, before replantation and 36 teeth in saline solution. Root development was categorized with respect to root formation and development of the apex into three groups, one-half-root formation to full root formation with open apex, full root formation with half-closed apex and full root formation with closed apex. Pulp survival and periodontal healing were assessed as successful when at the end of the observation period no pulp necrosis or ankylosis-related resorption was diagnosed. The mean observation time was 48 months. In the doxycycline group, 27 were diagnosed with pulp necrosis, 15 with ankylosis-related resorption and nine were extracted. In the saline group, 30 were diagnosed with pulp necrosis, 23 with ankylosis-related resorption and 11 were extracted. Regarding pulp survival and periodontal healing, no significant differences were found between the two groups. Teeth with immature root development showed significantly less pulp necrosis (P doxycycline or not. No significant differences were found between the two groups regarding age, storage, root development, splinting duration and observation time although the saline group had significantly longer extra-oral time (P doxycycline group. This study indicates that avulsed permanent teeth soaked in doxycycline do not show a better treatment outcome regarding pulp survival and periodontal healing compared with avulsed teeth placed only in saline solution. This finding is consistent regardless

  8. Eradication of Biofilm-Like Microcolony Structures of Borrelia burgdorferi by Daunomycin and Daptomycin but not Mitomycin C in Combination with Doxycycline and Cefuroxime.

    Science.gov (United States)

    Feng, Jie; Weitner, Megan; Shi, Wanliang; Zhang, Shuo; Zhang, Ying

    2016-01-01

    Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. While the majority of Lyme disease patients can resolve their symptoms if treated promptly, 10-20% of patients suffer from prolonged symptoms called post-treatment Lyme disease syndrome (PTLDS). Although the cause for PTLDS is unclear, one possibility is the presence of bacterial persisters not effectively cleared by the current Lyme antibiotics. Recent studies identified several drug candidates including daptomycin, daunomycin, doxorubicin, and mitomycin C that had good activity against B. burgdorferi persisters. However, their relative activities against B. burgdorferi persisters have not been evaluated under the same conditions. In this study, we tested the anti-persister activities of these drugs against both 7-day and 15-day old stationary phase cultures of B. burgdorferi individually as well as in combination with Lyme antibiotics doxycycline and cefuroxime (Ceftin). Our findings demonstrate daunomycin and daptomycin were more active than mitomycin C in single drug comparison at 10 and 20 μM, as well as in drug combinations with doxycycline and cefuroxime. In addition, daunomycin was more active than doxorubicin which correlated with their ability to stain and accumulate in B. burgdorferi. The two drug combination of doxycycline and cefuroxime was unable to eradicate biofilm-like microcolonies of B. burgdorferi persisters. However, the addition of either daunomycin or daptomycin to the doxycycline + cefuroxime combination completely eradicated the biofilm-like structures and produced no visible bacterial regrowth after 7 and 21 days, while the addition of doxorubicin was unable to prevent regrowth at either 7 or 21 day subculture. Mitomycin C in combination with doxycycline and cefuroxime caused no regrowth at 7 days but visible spirochetal regrowth occurred after 21 day subculture. Furthermore, we found that cefuroxime (Ceftin), the third

  9. Eradication of Biofilm-like Microcolony Structures of Borrelia burgdorferi by Daunomycin and Daptomycin but not Mitomycin C in Combination with Doxycycline and Cefuroxime

    Directory of Open Access Journals (Sweden)

    Jie eFeng

    2016-02-01

    Full Text Available Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. While the majority of Lyme disease patients can resolve their symptoms if treated promptly, 10-20% of patients suffer from prolonged symptoms called post-treatment Lyme disease syndrome (PTLDS. Although the cause for PTLDS is unclear, one possibility is the presence of bacterial persisters not effectively cleared by the current Lyme antibiotics. Recent studies identified several drug candidates including daptomycin, daunomycin, doxorubicin, and mitomycin C that had good activity against B. burgdorferi persisters. However, their relative activities against B. burgdorferi persisters have not been evaluated under the same conditions. In this study, we tested the anti-persister activities of these drugs against both 7-day and 15-day old stationary phase cultures of B. burgdorferi individually as well as in combination with Lyme antibiotics doxycycline and cefuroxime (Ceftin. Our findings demonstrate daunomycin and daptomycin were more active than mitomycin C in single drug comparison at 10 and 20 µM, as well as in drug combinations with doxycycline and cefuroxime. In addition, daunomycin was more active than doxorubicin which correlated with their ability to stain and accumulate in B. burgdorferi. The two drug combination of doxycycline and cefuroxime was unable to eradicate biofilm-like microcolonies of B. burgdorferi persisters. However, the addition of either daunomycin or daptomycin to the doxycycline + cefuroxime combination completely eradicated the biofilm-like structures and produced no visible bacterial regrowth after 7 days and 21 days, while the addition of doxorubicin was unable to prevent regrowth at either 7 day or 21 day subculture. Mitomycin C in combination with doxycycline and cefuroxime caused no regrowth at 7 days but visible spirochetal regrowth occurred after 21 day subculture. Furthermore, we found that

  10. Efficacy of Chitosan gel mucoadhesive containing Doxycycline associated or not to Meloxicam as adjuvant to treatment of gingivitis in dogs with periodontal disease

    Directory of Open Access Journals (Sweden)

    Rita de Cassia da Costa Silva

    2016-06-01

    Full Text Available ABSTRACT. Silva R.C.C., Campos D. R., Oliveira P., Laguna A.G.V., Magalhães V.S., Cid Y.P., Almeida M.B., Scott F.B. & Fernandes J.I. [Efficacy of Chitosan gel mucoadhesive containing Doxycycline associated or not to Meloxicam as adjuvant to treatment of gingivitis in dogs with periodontal disease.] Eficácia de um gel de Quitosano Mucoadesivo contendo Doxiciclina associada ou não ao Meloxicam como coadjuvante ao tratamento da gengivite em cães portadores de doença periodontal. Revista Brasileira de Medicina Veterinária, 38(Supl.2:40-44, 2016. Programa de Pós-Graduação em Medicina Veterinária, Universidade Federal Rural do Rio de Janeiro, BR 465 Km 7, Seropédica, RJ 23897-000, Brasil. E-mail: vetjulio@yahoo.com.br Periodontal disease is the highest occurrence condition in the pet clinic, affecting mainly older animals because of its characteristic of chronicity. Among the clinical signs observed in afflicted animals, gingivitis is the first to be observed. The goal of this study was to develop a mucoadhesive gel, containing doxycycline and meloxicam, and evaluate its efficacy as an adjuvant in the treatment of gingivitis induced by periodontal disease, with a clinical and histopathological rating. Eighteen Beagle dogs presenting gingivitis secondary to periodontal disease were divided into three experimental groups. Group I – animals treated with placebo formulation. Group II – Animals treated with a chitosan gel formulation containing doxycycline. Group III - Animals treated with a chitosan gel formulation containing doxycycline and meloxicam. All animals were treated for seven days, every twelve hours, in the gingival margin of the right maxilla. During the clinic evaluation, only the animals treated with the product containing doxycycline had improved. Contrasting, in the histopathologic evaluation, only animals treated with association of doxycycline and meloxicam presented improvements in their clinical score, although no

  11. Determination of the Mutant Selection Window and Evaluation of the Killing of Mycoplasma gallisepticum by Danofloxacin, Doxycycline, Tilmicosin, Tylvalosin and Valnemulin

    OpenAIRE

    Zhang, Nan; Ye, Xiaomei; Wu, Yuzhi; Huang, Zilong; Gu, Xiaoyan; Cai, Qinren; Shen, Xiangguang; Jiang, Hongxia; Ding, Huanzhong

    2017-01-01

    Mycoplasma gallisepticum is a common etiological cause of a chronic respiratory disease in chickens; its increasing antimicrobial resistance compromises the use of tetracyclines, macrolides and quinolones in the farm environment. Mutant selection window (MSW) determination was used to investigate the propensity for future resistance induction by danofloxacin, doxycycline, tilmicosin, tylvalosin and valnemulin. Killing of M. gallisepticum strain S6 by these antimicrobials was also studied by i...

  12. Use of Dapsone 5% Gel as Maintenance Treatment of Acne Vulgaris Following Completion of Oral Doxycycline and Dapsone 5% Gel Combination Treatment.

    Science.gov (United States)

    Kircik, Leon H

    2016-02-01

    Acne vulgaris is a common, chronic skin disease that requires long-term therapy. Oral antibiotics are a mainstay of treatment, but extended use is associated with the development of bacterial resistance. Topical therapies are often combined with oral antibiotics to achieve an initial improvement, after which the oral agents may be discontinued and the topical therapy used as maintenance. To assess the safety and efficacy of combination therapy with dapsone 5% gel with oral doxycycline hyclate 100mg, followed by monotherapy with dapsone 5% gel in improving and maintaining response in patients with moderate to severe acne. In this open-label study, all patients applied dapsone 5% gel twice daily along with doxycycline hyclate 100mg once daily for 12 weeks. Subjects who achieved a qualifying improvement at week 12 continued to the second phase of the study in which they applied only dapsone 5% gel twice daily for maintenance therapy of 12 more weeks. Subjects were evaluated for safety and efficacy at weeks 4, 8, 12, 16, 20, and 24. All subjects (n=30) in the initial phase qualified to enter the maintenance phase. 82% of participants maintained their treatment response (Investigator's Global Assessment score) at week 24. The regimen was safe and well tolerated. The combination oral doxycycline hyclate 100 mg with topical dapsone 5% gel twice daily is an effective and well-tolerated regimen to treat moderate to severe acne vulgaris. After discontinuation of doxycycline, topical dapsone 5% gel is effective at maintaining a therapeutic response. These data suggest that topical dapsone 5% gel can be used effectively for long-term acne maintenance treatment without the risk of developing antibiotic resistance.

  13. In vitro activities of amoxicillin-clavulanate, doxycycline, ceftazidime, imipenem, and trimethoprim-sulfamethoxazole against biofilm of Brazilian strains of Burkholderia pseudomallei.

    Science.gov (United States)

    Bandeira, Tereza de Jesus Pinheiro Gomes; Moreira, Camila Alencar; Brilhante, Raimunda Sâmia Nogueira; Castelo-Branco, Débora de Souza Collares Maia; Neto, Manoel Paiva de Araújo; Cordeiro, Rossana de Aguiar; Rodrigues, Terezinha de Jesus Santos; Rocha, Marcos Fábio Gadelha; Sidrim, José Júlio Costa

    2013-11-01

    This study aimed at investigating the in vitro activities of amoxicillin-clavulanate, doxycycline, ceftazidime, imipenem, and trimethoprim-sulfamethoxazole against Burkholderia pseudomallei in planktonic and biofilm forms, through broth microdilution and resazurin-based viability staining, respectively. In planktonic growth, the strains were susceptible to the drugs, while in biofilm growth, significantly higher antimicrobial concentrations were required, especially for ceftazidime and imipenem, surpassing the resistance breakpoints. These results highlight the importance of the routine evaluation of biofilm antimicrobial susceptibility.

  14. Untersuchung der Sensitivität von Chlamydien-Isolaten unter Verwendung verschiedener antibakterieller Wirkstoffe (Chlortetracyclin, Doxycyclin, Enrofloxacin, Difloxacin, Clarithromycin und Erythromycin)

    OpenAIRE

    Blanco Peña, Kinndle Marta

    2007-01-01

    Nach der Literaturübersicht wird die Methode zur Bestimmung der Antibiotikumempfindlichkeit von 27 Chlamydophila psittaci-Isolaten gegen Chlortetracyclin (CTC), Doxycyclin, Enrofloxacin, Difloxacin, Clarithromycin und Erythromycin - minimale Hemmkonzentration (MHK) - aufgeführt. Die MHK wird als die niedrigste Konzentration einer Substanz angesehen, die eben die Bildung reifer zytoplasmatischer Chlamydophila psittaci-Einschlüsse (infektiöse Partikel) verhindert. Als resistent werden Chlamydie...

  15. Randomized masked controlled clinical trial to compare 7-day and 14-day course length of doxycycline in the treatment of Mycoplasma felis infection in shelter cats.

    Science.gov (United States)

    Kompare, B; Litster, A L; Leutenegger, C M; Weng, H-Y

    2013-03-01

    The aim of this study was to compare the clinical and microbial efficacy of a 7-day or a 14-day course of doxycycline for the treatment of Mycoplasma felis-infected cats with clinical signs of upper respiratory tract disease (URTD) assessed using clinical scoring criteria. Cats were randomly allocated to either the Doxy-7 group (N=20; 7-day course of oral doxycyline liquid followed by 7-days placebo); or the Doxy-14 group (N=20; 14-day course of oral doxycycline). There were no significant differences in Mycoplasma load between groups at Day 1 or Day 7 (P>0.05), but at Day 14 mean Mycoplasma load was lower in the Doxy-14 group (P=0.01). Mycoplasma load reduced over Days 1-7 in each group (PMycoplasma load at Day 14 compared to Day 1 (Poral doxycycline produced superior microbial but not clinical results compared to a 7-day course of treatment. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Two types of Tet-On transgenic lines for doxycycline-inducible gene expression in zebrafish rod photoreceptors and a gateway-based tet-on toolkit.

    Directory of Open Access Journals (Sweden)

    Leah J Campbell

    Full Text Available The ability to control transgene expression within specific tissues is an important tool for studying the molecular and cellular mechanisms of development, physiology, and disease. We developed a Tet-On system for spatial and temporal control of transgene expression in zebrafish rod photoreceptors. We generated two transgenic lines using the Xenopus rhodopsin promoter to drive the reverse tetracycline-controlled transcriptional transactivator (rtTA, one with self-reporting GFP activity and one with an epitope tagged rtTA. The self-reporting line includes a tetracycline response element (TRE-driven GFP and, in the presence of doxycycline, expresses GFP in larval and adult rods. A time-course of doxycycline treatment demonstrates that maximal induction of GFP expression, as determined by the number of GFP-positive rods, is reached within approximately 24 hours of drug treatment. The epitope-tagged transgenic line eliminates the need for the self-reporting GFP activity by expressing a FLAG-tagged rtTA protein. Both lines demonstrate strong induction of TRE-driven transgenes from plasmids microinjected into one-cell embryos. These results show that spatial and temporal control of transgene expression can be achieved in rod photoreceptors. Additionally, system components are constructed in Gateway compatible vectors for the rapid cloning of doxycycline-inducible transgenes and use in other areas of zebrafish research.

  17. Increased incidence of postoperative infections during prophylaxis with cephalothin compared to doxycycline in intestinal surgery

    DEFF Research Database (Denmark)

    Baatrup, Gunnar; Nilsen, Roy M; Svensen, Rune

    2009-01-01

    BACKGROUND: The antibiotics used for prophylaxis during surgery may influence the rate of surgical site infections. Tetracyclines are attractive having a long half-life and few side effects when used in a single dose regimen. We studied the rate of surgical site infections during changing regimens...... of antibiotic prophylaxis in medium and major size surgery. METHODS: Prospective registration of surgical site infection following intestinal resections and hysterectomies was performed. Possible confounding procedure and patient related factors were registered. The study included 1541 procedures and 1489......, is an attractive candidate for antibiotic prophylaxis in medium and major size intestinal surgery....

  18. Doxycycline Inhibits IL-17-Stimulated MMP-9 Expression by Downregulating ERK1/2 Activation: Implications in Myogenic Differentiation

    Science.gov (United States)

    Obradović, Hristina; Krstić, Jelena; Kukolj, Tamara; Đorđević, Ivana Okić; Jauković, Aleksandra; Jovčić, Gordana

    2016-01-01

    Interleukin 17 (IL-17) is a cytokine with pleiotropic effects associated with several inflammatory diseases. Although elevated levels of IL-17 have been described in inflammatory myopathies, its role in muscle remodeling and regeneration is still unknown. Excessive extracellular matrix degradation in skeletal muscle is an important pathological consequence of many diseases involving muscle wasting. In this study, the role of IL-17 on the expression of matrix metalloproteinase- (MMP-) 9 in myoblast cells was investigated. The expression of MMP-9 after IL-17 treatment was analyzed in mouse myoblasts C2C12 cell line. The increase in MMP-9 production by IL-17 was concomitant with its capacity to inhibit myogenic differentiation of C2C12 cells. Doxycycline (Doxy) treatment protected the myogenic capacity of myoblasts from IL-17 inhibition and, moreover, increased myotubes hypertrophy. Doxy blocked the capacity of IL-17 to stimulate MMP-9 production by regulating IL-17-induced ERK1/2 MAPK activation. Our results imply that MMP-9 mediates IL-17's capacity to inhibit myoblast differentiation during inflammatory diseases and indicate that Doxy can modulate myoblast response to inflammatory induction by IL-17. PMID:28042204

  19. HPLC and chemometrics-assisted UV-spectroscopy methods for the simultaneous determination of ambroxol and doxycycline in capsule

    Science.gov (United States)

    Hadad, Ghada M.; El-Gindy, Alaa; Mahmoud, Waleed M. M.

    2008-08-01

    High-performance liquid chromatography (HPLC) and multivariate spectrophotometric methods are described for the simultaneous determination of ambroxol hydrochloride (AM) and doxycycline (DX) in combined pharmaceutical capsules. The chromatographic separation was achieved on reversed-phase C 18 analytical column with a mobile phase consisting of a mixture of 20 mM potassium dihydrogen phosphate, pH 6-acetonitrile in ratio of (1:1, v/v) and UV detection at 245 nm. Also, the resolution has been accomplished by using numerical spectrophotometric methods as classical least squares (CLS), principal component regression (PCR) and partial least squares (PLS-1) applied to the UV spectra of the mixture and graphical spectrophotometric method as first derivative of the ratio spectra ( 1DD) method. Analytical figures of merit (FOM), such as sensitivity, selectivity, analytical sensitivity, limit of quantitation and limit of detection were determined for CLS, PLS-1 and PCR methods. The proposed methods were validated and successfully applied for the analysis of pharmaceutical formulation and laboratory-prepared mixtures containing the two component combination.

  20. Doxiciclina em pacientes com linfangioleiomiomatose: biomarcadores e resposta funcional pulmonar Doxycycline use in patients with lymphangioleiomyomatosis: biomarkers and pulmonary function response

    Directory of Open Access Journals (Sweden)

    Suzana Pinheiro Pimenta

    2013-02-01

    Full Text Available OBJETIVO: Avaliar o bloqueio da metaloproteinase da matriz (MMP-2 e da MMP-9 e a variação do VEF1 em pacientes com linfangioleiomiomatose (LAM após o uso de doxiciclina, um conhecido inibidor de MMP, durante 12 meses. MÉTODOS: Ensaio clínico aberto de braço único no qual as pacientes com diagnóstico de LAM receberam doxiciclina (100 mg/dia durante 12 meses. Elas foram submetidas a prova de função pulmonar completa, teste de caminhada de seis minutos, avaliação da qualidade de vida e coleta de amostras séricas e urinárias para dosagem de MMP-2, MMP-9 e VEGF-D antes do início do tratamento com doxiciclina e após 6 e 12 meses de tratamento. RESULTADOS: Trinta e uma pacientes com LAM receberam doxiciclina durante 12 meses. Embora tenha havido um bloqueio efetivo da MMP-9 urinária e da MMP-2 sérica após o tratamento, os níveis séricos de MMP-9 e VEGF-D permaneceram estáveis. Com base na resposta à doxiciclina (determinada pela variação do VEF1, as pacientes foram divididas em dois grupos: respondedoras (doxi-R; n = 13 e não respondedoras (doxi-NR; n = 18. As pacientes com alterações espirométricas leves apresentaram melhor resposta à doxiciclina. Os efeitos colaterais mais comuns foram epigastralgia, náusea e diarreia, todos de leve intensidade. CONCLUSÕES: Em pacientes com LAM, o tratamento com doxiciclina resulta em um bloqueio eficaz das MMP, além de melhorar a função pulmonar e a qualidade de vida daqueles com doença menos grave. No entanto, esses benefícios não parecem estar relacionados ao bloqueio das MMP, o que sugere um mecanismo de ação diferente. (Registro Brasileiro de Ensaios Clínicos - ReBEC; número de identificação RBR-6g8yz9 [http://www.ensaiosclinicos.gov.br]OBJECTIVE: To assess blockade of matrix metalloproteinase (MMP-2 and MMP-9, as well as the variation in FEV1, in patients with lymphangioleiomyomatosis (LAM treated with doxycycline (a known MMP inhibitor for 12 months. METHODS: An open

  1. No evidential correlation between veterinary antibiotic degradation ability and resistance genes in microorganisms during the biodegradation of doxycycline.

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    Wen, Xin; Wang, Yan; Zou, Yongde; Ma, Baohua; Wu, Yinbao

    2018-01-01

    Biodegradation of antibiotic residues in the environment by microorganisms may lead to the generation of antibiotic resistance genes (ARGs), which are of great concern to human health. The aim of this study was to determine whether there is a relationship between the ability to degrade antibiotic doxycycline (DOX) and the development of resistance genes in microorganisms. We isolated and identified ten bacterial strains from a vegetable field that had received long-term manure application as fertilizer and were capable of surviving in a series of DOX concentrations (25, 50, 80, and 100mg/L). Our results showed no evidential correlation between DOX degradation ability and the development of resistance genes among the isolated microorganisms that had high DOX degradation capability (P > 0.05). This was based on the fact that Escherichia sp. and Candida sp. were the most efficient bacterial strains to degrade DOX (92.52% and 91.63%, respectively), but their tetracycline resistance genes showed a relatively low risk of antibiotic resistance in a 7-day experiment. Moreover, the tetM of the ribosomal protection protein genes carried by these two preponderant bacteria was five-fold higher than that carried by other isolates (P < 0.05). Pearson correlations between the Ct/C0 of DOX and tet resistance genes of three isolates, except for Escherichia sp. and Candida sp., showed remarkable negative correlations (P < 0.05), mainly because tetG markedly increased during the DOX degradation process. Our results concluded that the biodegradation of antibiotic residues may not necessarily lead to the development of ARGs in the environment. In addition, the two bacteria that we isolated, namely, Escherichia sp. and Candida sp., are potential candidates for the engineering of environmentally friendly bacteria. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Role of doxycycline to resolve different types of non-malignant lung and pleural pathology: The results of a pilot observation

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    Parthasarathi Bhattacharyya

    2015-01-01

    Full Text Available Background: Lung lesions may develop from tissue reactions to known or unknown stimuli and present with different morphological descriptions. The pathogenesis may be induced and maintained by different bioactive substances, of which, the upregulation matrix metalloproteinases (MMPs play a vital role. Inhibition of the MMPs, therefore, may be a prospective mode of therapy for such lesions. Materials and Methods: A number of patients with lung lesions of different morphologies and presentations were treated empirically with long-term oral doxycycline (100 mg BID upon exclusion of malignancy and infection in an open, single-arm, prospective, observational pilot study. The effect of the treatment was recorded on serial x-rays/computed tomography (CT scans and the impact of treatment was measured with a visual analog scale (VAS or a Likert-like scale. Furthermore, six independent pulmonologists′ opinion (expressed on a ′0′ to ′100′ scale were pooled with regard to the significance and the expectedness of such a change. Results: Twenty-six patients (mean age 49.33 years and male: female ratio = 10:3 with different types of pulmonary parenchymal/pleural lesions were treated with long-term oral doxycycline for a mean duration of 386.88 days related to the available radiological comparison. They showed a mean improvement of 3.99 on the Likert-like scale and 78% on the VAS scale. The mean significance of the change was 83.33%, with a mean expectedness of 18% as per the pooled opinion of the pulmonologists. Inference: The significant and unexpected resolution of different tissue lesions from long-term doxycycline appears to be a novel observation. This needs proper scientific validation.

  3. Efficacy of levofloxacin-doxycycline-based rescue therapy for Helicobacter pylori eradication: A prospective open-label trial in Saudi Arabia

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    Fahad I Alsohaibani

    2017-01-01

    Full Text Available Background: Helicobacter pylori eradication is achieved in 60%–80% with first-line therapy. Different second-line therapeutic options are available. However, the success of second-line therapy has not been addressed or reported from Saudi Arabia. Objectives: The primary objective was to evaluate the efficacy of the 10-day course of levofloxacin, doxycycline and esomeprazole in non-responders to first-line therapies for H. pylori eradication in Saudi Arabia. Secondary objectives included were symptoms' response to treatment, factors associated with eradication of H. pylori and adverse events associated with the treatment. Patients and Methods: A prospective, open-label, single-arm study was conducted. Patients were recruited from a tertiary care hospital in Saudi Arabia from June 2013 to April 2014. A total of 55 patients had previously received standard triple therapy and/or sequential therapy from 2011 to 2014 and failed to eradicate the infection. The rescue treatment was given for 10 days consisting of levofloxacin 500 mg once daily, doxycycline 100 mg twice daily and esomeprazole 20 mg twice daily. Urea breath test (UBT was done at a minimum of 6 weeks after completion of the treatment to confirm the H. pylori eradication. Results: From 55 patients recruited, 32 had failed to respond to previous standard triple therapy, 15 patients failed to respond to sequential therapy and 8 patients failed to both regimens. Persistent H. pylori infection was confirmed by rapid urease test, histology or UBT. H. pylori eradication was achieved in 20 out of 51 patients (39.22%, per protocol analysis, 36.36% by intention to treat analysis. Therapy was well tolerated and side effects were generally mild. Conclusion: Rescue treatment with levofloxacin and doxycycline-based therapy for 10 days was well tolerated but effective only in 39.22% of patients infected with H. pylori in Saudi Arabia. More trials to determine the most efficacious rescue therapy in

  4. Idiopathic Facial Aseptic Granuloma in a 13-Year-Old Boy Dramatically Improved with Oral Doxycycline and Topical Metronidazole: Evidence for a Link with Childhood Rosacea

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    Camille Orion

    2016-07-01

    Full Text Available Idiopathic facial aseptic granuloma (IFAG is a rare, benign pediatric dermatological lesion that occurs in children between 8 months and 13 years of age. The pathogenesis of IFAG is still unclear but it is likely to be associated with granulomatous rosacea in childhood. Here we describe a case of IFAG in a 13-year-old boy who showed a dramatic response to oral doxycycline and topical metronidazole, which supports the hypothesis that IFAG may belong to the spectrum of rosacea.

  5. Doxycycline Leads to Sterility and Enhanced Killing of Female Onchocerca volvulus Worms in an Area With Persistent Microfilaridermia After Repeated Ivermectin Treatment: A Randomized, Placebo-Controlled, Double-Blind Trial.

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    Debrah, Alexander Yaw; Specht, Sabine; Klarmann-Schulz, Ute; Batsa, Linda; Mand, Sabine; Marfo-Debrekyei, Yeboah; Fimmers, Rolf; Dubben, Bettina; Kwarteng, Alexander; Osei-Atweneboana, Mike; Boakye, Daniel; Ricchiuto, Arcangelo; Büttner, Marcelle; Adjei, Ohene; Mackenzie, Charles D; Hoerauf, Achim

    2015-08-15

    Ivermectin (IVM) has been the drug of choice for the treatment of onchocerciasis. However, there have been reports of persistent microfilaridermia in individuals from an endemic area in Ghana after many rounds of IVM, raising concerns of suboptimal response or even the emergence of drug resistance. Because it is considered risky to continue relying only on IVM to combat this phenomenon, we assessed the effect of targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline for these individuals with suboptimal response. One hundred sixty-seven patients, most of them with multiple rounds of IVM, were recruited in areas with IVM suboptimal response and treated with 100 mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment, patients took part in standard IVM treatment. At 20 months after treatment, 80% of living female worms from the placebo group were Wolbachia positive, whereas only 5.1% in the doxycycline-treated group contained bacteria. Consistent with interruption of embryogenesis, none of the nodules removed from doxycycline-treated patients contained microfilariae, and 97% of those patients were without microfilaridermia, in contrast to placebo patients who remained at pretreatment levels (P volvulus is effective in clearing microfilariae in the skin of onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Strategies can now be developed that include doxycycline to control onchocerciasis in areas where infections persist despite the frequent use of IVM. ISRCTN 66649839. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  6. Preparation, characterization and pharmacokinetics of doxycycline hydrochloride and florfenicol polyvinylpyrroliddone microparticle entrapped with hydroxypropyl-β-cyclodextrin inclusion complexes suspension.

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    Li, Xianqiang; Xie, Shuyu; Pan, Yuanhu; Qu, Wei; Tao, Yanfei; Chen, Dongmei; Huang, Lingli; Liu, Zhenli; Wang, Yulian; Yuan, Zonghui

    2016-05-01

    In order to effectively control the bacterial pneumonia in pigs, doxycycline hydrochloride (DoxHcl) and florfenicol (FF) microparticle suspension together with inclusion complexes was prepared by using hydroxypropyl-β-cyclodextrin (HP-β-CD) as host molecules, polyvinylpyrroliddone (PVP) as polymer carriers and hydroxypropyl methyl cellulose (HPMC) as suspending agents. In vitro antibacterial activity, properties, stability and pharmacokinetics of the suspension were studied. The results demonstrated that DoxHcl and FF had a synergistic or additive antibacterial activity against Streptococcus suis, Actinobacillus pleuropneumoniae and Haemophilus parasuis. The size, polydispersity index and zeta potential of microparticles were 1.46 ± 0.06 μm, 0.30 ± 0.02 and 1.53 ± 0.04 mV, respectively. The encapsulation efficiency (EE) of DoxHcl and FF was 45.28% ± 3.30% and 89.69% ± 2.71%, respectively. The re-dispersed time and sedimentation rate of the suspension were 1 min and 1. The suspension went through the 9-gage needle smoothly with withdrawal volume of 9.12 ± 0.87 mL/min. The suspension showed good stability when stored away from light, no irritation at the injection site and sustained release in PBS buffer. After intramuscular administration to pig, DoxHcl and FF could maintain over 0.15 μg/mL for 72 h. Compared to the control injection, the suspension increased the elimination half-life (T½ke) as well as mean residence time (MRT) of DoxHcl from 5.73 to 9.77 h and from 12.02 to 18.81 h, and those of FF from 12.02 to 26.19 h and from 12.02 to 28.16 h, respectively. The suspension increased the bioavailability of DoxHcl and FF by 1.74 and 1.13-fold, respectively. These results suggest that the compound suspension is a promising formulation for pig pneumonia therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Ultra-Sensitive Nano Optical Sensor Samarium-Doxycycline Doped in Sol Gel Matrix for Assessment of Glucose Oxidase Activity in Diabetics Disease.

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    Tharwat, Marwa M; Attia, M S; Alghamdi, M S; Mahros, Amr M

    2017-07-11

    A low cost and very sensitive method for the determination of the activity of glucose oxidase enzyme in different diabetics serum samples was developed. The method based on the assessment of the H2O2 concentration produced from the reaction of the glucose oxidase (GOx) enzyme with glucose as substrate in the serum of diabetics patients by nano optical sensor Sm-doxycycline doped in sol gel matrix. H2O2 enhances the luminescence intensity of all bands of the nano Sm-doxycycline complex [Sm-(DC)2](+) doped in sol-gel matrix, especially the 645 nm band at λex = 400 nm and pH 7.0 in water. The influence of the different analytical parameters that affect the luminescence intensity of the nano optical sensor, e.g. pH, H2O2 concentration and foreign ions concentrations were studied. The remarkable enhancement of the luminescence intensity of nano optical sensor [Sm-(DC)2](+) complex in water at 645 nm by the addition of various concentrations of H2O2 was successfully used as an optical sensor for the assessment of the activity of the glucose oxidase enzyme in different diabetics serum samples. The calibration plot was achieved over the activity range 0.1-240 U/L with a correlation coefficient of 0.999 and a detection limit of 0.05 U/L.

  8. Determination of the Mutant Selection Window and Evaluation of the Killing of Mycoplasma gallisepticum by Danofloxacin, Doxycycline, Tilmicosin, Tylvalosin and Valnemulin.

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    Nan Zhang

    Full Text Available Mycoplasma gallisepticum is a common etiological cause of a chronic respiratory disease in chickens; its increasing antimicrobial resistance compromises the use of tetracyclines, macrolides and quinolones in the farm environment. Mutant selection window (MSW determination was used to investigate the propensity for future resistance induction by danofloxacin, doxycycline, tilmicosin, tylvalosin and valnemulin. Killing of M. gallisepticum strain S6 by these antimicrobials was also studied by incubating M. gallisepticum into medium containing the compounds at the minimal concentration that inhibits colony formation by 99% (MIC99 and the mutant prevention concentration (MPC. Based on the morphology and colony numbers of M. gallisepticum on agar plates, the four kinds of sera in the order of the applicability for culturing M. gallisepticum were swine serum > horse serum > bovine serum > mixed serum. The MPC/MIC99 values for each agent were as follows: danofloxacin > tilmicosin > tylvalosin > doxycycline > valnemulin. MPC generated more rapid and greater magnitude killing than MIC99 against M. gallisepticum. Under exposure of 105-109 CFU/mL at MPC drug levels, valnemulin had the slowest rate of reduction in viable organisms and danofloxacin had the highest rate of reduction.

  9. Determination of the Mutant Selection Window and Evaluation of the Killing of Mycoplasma gallisepticum by Danofloxacin, Doxycycline, Tilmicosin, Tylvalosin and Valnemulin.

    Science.gov (United States)

    Zhang, Nan; Ye, Xiaomei; Wu, Yuzhi; Huang, Zilong; Gu, Xiaoyan; Cai, Qinren; Shen, Xiangguang; Jiang, Hongxia; Ding, Huanzhong

    2017-01-01

    Mycoplasma gallisepticum is a common etiological cause of a chronic respiratory disease in chickens; its increasing antimicrobial resistance compromises the use of tetracyclines, macrolides and quinolones in the farm environment. Mutant selection window (MSW) determination was used to investigate the propensity for future resistance induction by danofloxacin, doxycycline, tilmicosin, tylvalosin and valnemulin. Killing of M. gallisepticum strain S6 by these antimicrobials was also studied by incubating M. gallisepticum into medium containing the compounds at the minimal concentration that inhibits colony formation by 99% (MIC99) and the mutant prevention concentration (MPC). Based on the morphology and colony numbers of M. gallisepticum on agar plates, the four kinds of sera in the order of the applicability for culturing M. gallisepticum were swine serum > horse serum > bovine serum > mixed serum. The MPC/MIC99 values for each agent were as follows: danofloxacin > tilmicosin > tylvalosin > doxycycline > valnemulin. MPC generated more rapid and greater magnitude killing than MIC99 against M. gallisepticum. Under exposure of 105-109 CFU/mL at MPC drug levels, valnemulin had the slowest rate of reduction in viable organisms and danofloxacin had the highest rate of reduction.

  10. Doxycycline and IL-8 modulation in a line of human alveolar epithelium: more evidence for the anti-inflammatory function of some antimicrobials

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    Blum JE

    2013-04-01

    Full Text Available No abstract available. Article truncated at 150 words. Beta blockers for severe systolic dysfunction; antibiotics for peptic ulcer disease. These are just a few examples of the many unpredicted consequences of medication intervention. Rheumatology has known of the disease modifying anti-rheumatic drug (DMARD capacity of second generation tetracyclines including doxycycline (1. This has actually led to investigations attempting to identify organisms possibly serving as substrates for inflammatory processes including rheumatoid arthritis and even atherosclerosis. Generally, this has been unsuccessful and the conclusion that doxycycline has intrinsic anti-inflammatory properties has become suspect (2,3. Experience with higher generation macrolides like azithromycin further lends credence to this concept of antibiotics as intrinsically anti-inflammatory (4. There is a body of data suggesting inhibition of cytokine expression by this drug. In diseases like cystic fibrosis where even very high intracellular concentrations of macrolide have no significant activity against pseudomonas species but the drug therapy does appear to modify disease course further supports this …

  11. Cloning and characterization of an adenoviral vector for highly efficient and doxycycline – suppressible expression of bioactive human single – chain interleukin 12 in colon cancer

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    Schäfer Hansjörg

    2007-06-01

    Full Text Available Abstract Background Interleukin-12 (IL-12 is well characterized to induce cellular antitumoral immunity by activation of NK-cells and T-lymphocytes. However, systemic administration of recombinant human IL-12 resulted in severe toxicity without perceptible therapeutic benefit. Even though intratumoral expression of IL-12 leads to tumor regression and long-term survival in a variety of animal models, clinical trials have not yet shown a significant therapeutic benefit. One major obstacle in the treatment with IL-12 is to overcome the relatively low expression of the therapeutic gene without compromising the safety of such an approach. Our objective was to generate an adenoviral vector system enabling the regulated expression of very high levels of bioactive, human IL-12. Results High gene expression was obtained utilizing the VP16 herpes simplex transactivator. Strong regulation of gene expression was realized by fusion of the VP16 to a tetracycline repressor with binding of the fusion protein to a flanking tetracycline operator and further enhanced by auto-regulated expression of its fusion gene within a bicistronic promoter construct. Infection of human colon cancer cells (HT29 at a multiplicity of infection (m.o.i. of 10 resulted in the production of up to 8000 ng/106 cells in 48 h, thus exceeding any published vector system so far. Doxycycline concentrations as low as 30 ng/ml resulted in up to 5000-fold suppression, enabling significant reduction of gene expression in a possible clinical setting. Bioactivity of the human single-chain IL-12 was similar to purified human heterodimeric IL-12. Frozen sections of human colon cancer showed high expression of the coxsackie adenovirus receptor with significant production of human single chain IL-12 in colon cancer biopsies after infection with 3*107 p.f.u. Ad.3r-scIL12. Doxycycline mediated suppression of gene expression was up to 9000-fold in the infected colon cancer tissue. Conclusion VP16

  12. Doxycycline as an inhibitor of p-glycoprotein in the alpaca for the purpose of maintaining avermectins in the CNS during treatment for parelaphostrongylosis.

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    Agbedanu, Prince N; Anderson, Kristi L; Brewer, Matthew T; Carlson, Steve A

    2015-09-15

    Meningeal worms (Parelaphostrongylus tenuis) are a common malady of alpacas, often refractory to conventional treatments. Ivermectin is a very effective anthelmintic used against a variety of parasites but this drug is not consistently effective against alpaca meningeal worms once the parasite has gained access to the CNS, even if used in a protracted treatment protocol. Ivermectin is not effective against clinical cases of P. tenuis, raising the possibility that the drug is not sustained at therapeutic concentrations in the central nervous system (CNS). A specific protein (designated as p-glycoprotein (PGP)) effluxes ivermectin from the brain at the blood-brain barrier, thus hampering the maintenance of therapeutic concentrations of the drug in the CNS. Minocycline is a synthetic tetracycline antibiotic with an excellent safety profile in all animals tested to date. Minocycline has three unique characteristics that could be useful for treating meningeal worms in conjunction with ivermectin. First, minocycline is an inhibitor of PGP at the blood-brain barrier and this inhibition could maintain effective concentrations of ivermectin in the brain and meninges. Second, minocycline protects neurons in vivo through a number of different mechanisms and this neuroprotection could alleviate the potential untoward neurologic effects of meningeal worms. Third, minocycline is a highly lipid-soluble drug, thus facilitating efficient brain penetration. We thus hypothesized that minocycline will maintain ivermectin, or a related avermectin approved in ruminants (abamectin, doramectin, or eprinomectin), in the alpaca CNS. To test this hypothesis, we cloned the gene encoding the alpaca PGP, expressed the alpaca PGP in a heterologous expression system involving MDCK cells, and measured the ability of minocycline to inhibit the efflux of avermectins from the MDCK cells; doxycycline was used as a putative negative control (based on studies in other species). Our in vitro studies

  13. Effects of a timely therapy with doxycycline on the left ventricular remodeling according to the pre-procedural TIMI flow grade in patients with ST-elevation acute myocardial infarction.

    Science.gov (United States)

    Cerisano, Giampaolo; Buonamici, Piergiovanni; Valenti, Renato; Moschi, Guia; Taddeucci, Enrico; Giurlani, Letizia; Migliorini, Angela; Vergara, Ruben; Parodi, Guido; Sciagrà, Roberto; Romito, Roberta; Colonna, Paolo; Antoniucci, David

    2014-07-01

    Doxycycline has been demonstrated to reduced left ventricular (LV) remodeling, but its effect in patients with ST-elevation myocardial infarction (STEMI) and a baseline occluded [thrombolysis in myocardial infarction (TIMI) flow grade ≤1] infarct-related artery (IRA) is unknown. According to the baseline TIMI flow grade, 110 patients with a first STEMI were divided into 2 groups. Group 1: 77 patients with TIMI flow ≤1 (40 patients treated with doxycycline and 37 with standard therapy, respectively), and a Group 2: 33 patients with TIMI flow 2-3 (15 patients treated with doxycycline and 18 with standard therapy, respectively). The two randomized groups were well matched in baseline characteristics. A 2D-Echo was performed at baseline and at 6 months, together with a coronary angiography, for the remodeling and IRA patency assessment, respectively. The LV end-diastolic volume index (LVEDVi) decreased in Group 2 [-3 mL/m(2) (IQR: -12 to 4 mL/m(2))], and increased in Group 1 [6 mL/m(2) (IQR: -2 to 14 mL/m(2))], (p = 0.001). In Group 2, LVEDVi reduction was similar regardless of drug therapy, while in Group 1 the LVEDVi was smaller in patients treated with doxycycline as compared to control [3 mL/m(2) (IQR: -3 to 8 mL/m(2)) vs. 10 mL/m(2) (IQR: 1-27 mL/m(2)), p = 0.006]. A similar pattern was observed also for LV end-systolic volume and ejection fraction. In STEMI patients at higher risk, as those with a baseline TIMI flow grade ≤1, doxycycline reduces LV remodeling.

  14. Generation of an Rx-tTA: TetOp-Cre knock-in mouse line for doxycycline regulated Cre activity in the Rx expression domain.

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    Timothy F Plageman

    Full Text Available Genetic deletion of mouse genes has played a crucial role in our understanding of embryonic eye development. Transgenic, tissue specific Cre recombinase expression in various eye structures has facilitated these experiments. However, an early expressing, temporally-regulated, optic vesicle-specific Cre line has not been available. In this report, we detail the generation and analysis of a knock-in, inducible Cre line designed to drive recombination specifically within the Rx expression domain. Crossing this line with a reporter line demonstrates that recombination can be mediated within the early optic vesicle and throughout retinal development. Recombination can also be mediated in the Rx-expressing, ventral diencephalon and future posterior pituitary gland. Furthermore, it was demonstrated that dietary doxycycline could effectively modulate Cre activity. This line has the potential to facilitate conditional knock-out experimentation to study early retina and/or posterior pituitary development.

  15. Excitation energy transfer in europium chelate with doxycycline in the presence of a second ligand in micellar solutions of nonionic surfactants

    Science.gov (United States)

    Smirnova, T. D.; Shtykov, S. N.; Kochubei, V. I.; Khryachkova, E. S.

    2011-01-01

    The complexation of Eu3+ with doxycycline (DC) antibiotic in the presence of several second ligands and surfactant micelles of different types is studied by the spectrophotometric and luminescence methods. It is found that the efficiency of excitation energy transfer in Eu3+-DC chelate depends on the nature of the second ligand and surfactant micelles. Using thenoyltrifluoroacetone (TTA) as an example, it is shown that the second ligand additionally sensitizes the europium fluorescence, and the possibility of intermediate sensitization of DC and then of europium is shown by the example of 1,10-phenanthroline. In all cases, the excitation energy transfer efficiency was increased due to the so-called antenna effect. The decay kinetics of the sensitized fluorescence of the binary and mixed-ligand chelates in aqueous and micellar solutions of nonionic surfactants is studied and the relative quantum yields and lifetimes of fluorescence are determined.

  16. Oral doxycycline, niacinamide and prednisolone used to treat bilateral nodular granulomatous conjunctivitis of the third eyelid in an Australian Kelpie dog.

    Science.gov (United States)

    Hurn, Simon; Mc Cowan, Christina; Turner, Andrew

    2005-01-01

    A 5-year-old, female neutered, Australian Kelpie presented with a 2-month history of dramatic bilateral erythematous thickening of the third eyelids. Ophthalmic examination demonstrated raised, pink to red, irregular thickening of the entire palpebral surface of both third eyelids. There were no other ocular abnormalities. A surgical biopsy was taken from each third eyelid. Histopathologic examination revealed sheets of macrophages, plasma cells, lymphocytes, and occasional fibroblasts and neutrophils infiltrating the third eyelid stroma. A diagnosis of chronic granulomatous conjunctivitis was made. Grossly and histopathologically this case closely resembles previously described cases of nodular granulomatous conjunctivitis involving the third eyelids of Collie dogs. This report describes an unusual case of nodular granulomatous conjunctivitis isolated to the third eyelids in an Australian Kelpie. Resolution of the condition was achieved with a combination of oral doxycycline, niacinamide and prednisolone.

  17. Assessment of parasitological findings in heartworm-infected beagles treated with Advantage Multi® for dogs (10% imidacloprid + 2.5% moxidectin) and doxycycline.

    Science.gov (United States)

    Savadelis, Molly D; Ohmes, Cameon M; Hostetler, Joe A; Settje, Terry L; Zolynas, Robert; Dzimianski, Michael T; Moorhead, Andrew R

    2017-05-19

    Anecdotal reports support the position that the adulticidal heartworm treatment utilizing doxycycline and Advantage Multi®/Advocate® for Dogs (10% imidacloprid + 2.5% moxidectin) has successfully converted antigen-positive dogs to antigen-negative. To date, no controlled experimental studies have demonstrated the adulticidal efficacy of this treatment regimen. The aim of this study was to evaluate the parasitological and clinical efficacy of Advantage Multi® for Dogs (IMD + MOX) and doxycycline in heartworm-infected beagles. This study utilized 16 dogs, 8 dogs in each of non-treated control and treated groups. A total of 16 adult Dirofilaria immitis (Missouri strain) were surgically transplanted into the jugular vein of each study dog. The treatment regimen of monthly IMD + MOX topically (per labeled dosage and administration) for 10 months and 10 mg/kg doxycycline BID orally for 30 days was initiated 30 days post-surgical transplant. Echocardiograms, radiographs, complete blood counts, clinical chemistry profiles, heartworm antigenemia and microfilaremia were evaluated every 4 weeks. Serum samples were assayed for heartworm antigen using the DiroCHEK® heartworm antigen test. The DiroCHEK® was performed according to the manufacturer's recommendations and read using a spectrophotometer at 490 nm. All dogs tested positive for the presence of heartworm antigen post-surgical transplant and prior to treatment. Heartworm antigen levels began declining in treated dogs 3 months post-treatment. Non-treated control dogs remained antigen-positive. No microfilariae were detected in treated dogs after 21 days post-treatment. At necropsy, adult heartworms were recovered from all non-treated control dogs with a range of 10-12 adult worms/dog for an average recovery of 10.6 adult heartworms/dog. In the IMD + MOX- and doxycycline-treated dogs, the range of adult heartworms recovered was 0-2 adult worms/dog, with five dogs having no adult heartworms

  18. Simultaneous UHPLC-UV analysis of hydroxychloroquine, minocycline and doxycycline from serum samples for the therapeutic drug monitoring of Q fever and Whipple's disease.

    Science.gov (United States)

    Armstrong, Nicholas; Richez, Magali; Raoult, Didier; Chabriere, Eric

    2017-08-15

    A fast UHPLC-UV method was developed for the simultaneous analysis of Hydroxychloroquine, Minocycline and Doxycycline drugs from 100μL of human serum samples. Serum samples were extracted by liquid-liquid extraction and injected into a phenyl hexyl reverse phase column. Compounds were separated using a mobile phase linear gradient and monitored by UV detection at 343nm. Chloroquine and Oxytetracycline were used as internal standards. Lower and upper limits of quantifications, as well as the other levels of calibration, were validated with acceptable accuracy (<15% deviation) and precision (<15% coefficient of variation) according to the European Medicines Agency guidelines. This new method enables cost and time reduction and was considered suitable for the clinical laboratory. It is the first published assay for the therapeutic drug monitoring of patients diagnosed with Q fever or Whipple's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Tacrolimus therapy for dermal arteritis of the nasal philtrum refractory to surgery and anti-inflammatory therapy (doxycycline/niacinamide and topical fluocinolone) in a dog.

    Science.gov (United States)

    Banovic, Frane; Jerry, Carmen; Howerth, Elizabeth

    2018-02-01

    Dermal arteritis of the nasal philtrum is a rarely reported condition commonly affecting large breed dogs. To describe the effective treatment of nasal philtrum arteritis with topical tacrolimus in one dog. A 9-year-old, intact male German shorthair pointer dog was presented with well-demarcated deep erythematous ulcers targeting exclusively the skin of the nasal philtrum, accompanied by frequent series of haemorrhage. Complete blood count, serum chemistry profile, urinalysis, histopathological examination and immunohistochemistry of skin biopsies. The presence of a V-shaped ulcer with subendothelial spindle cell proliferation resulting in stenosis of dermal arteries and arterioles on histological evaluation, together with a well-demarcated deep nasal philtrum ulcer was consistent with arteritis of the nasal philtrum. Treatment was initiated with twice daily oral doxycycline and niacinamide in conjunction with topical fluocinolone cream. Over the course of two years, the lesions progressed with frequent bleeding episodes. A novel surgical approach provided deep resection of all grossly affected tissue; four months later a recurrence of fissures and occasional mild bleeding from the original site was noted and there was no improvement after another two months of oral doxycycline/niacinamide and topical fluocinolone treatment. Topical application of 0.1% tacrolimus twice daily resulted in complete healing of the ulceration and normalization of the epidermis. Over the subsequent 15 months, the dog's lesions remained in remission with topical tacrolimus application twice daily. Topical tacrolimus ointment appeared effective at inducing and maintaining lesion remission in this dog with nasal philtrum arteritis. © 2017 ESVD and ACVD.

  20. Complementation of a Saccharomyces cerevisiae ERG11/CYP51 (Sterol 14α-Demethylase) Doxycycline-Regulated Mutant and Screening of the Azole Sensitivity of Aspergillus fumigatus Isoenzymes CYP51A and CYP51B▿

    Science.gov (United States)

    Martel, Claire M.; Parker, Josie E.; Warrilow, Andrew G. S.; Rolley, Nicola J.; Kelly, Steven L.; Kelly, Diane E.

    2010-01-01

    Aspergillus fumigatus sterol 14α-demethylase isoenzymes CYP51A and CYP51B were heterologously expressed in a Saccharomyces cerevisiae mutant (YUG37-erg11), wherein native ERG11/CYP51 expression is controlled using a doxycycline-regulatable promoter. When cultured in the presence of doxycycline, recombinant YUG37-pcyp51A and YUG37-pcyp51B yeasts were able to synthesize ergosterol and grow; a control strain harboring reverse-oriented cyp51A could not. YUG37-pcyp51A and YUG37-pcyp51B constructs showed identical sensitivity to itraconazole, posaconazole, clotrimazole, and voriconazole. Conversely, YUG37-pcyp51A withstood 16-fold-higher concentrations of fluconazole than YUG37-pcyp51B (8 and 0.5 μg ml−1, respectively). PMID:20733045

  1. Rosacea: Diagnosis and Treatment.

    Science.gov (United States)

    Oge', Linda K; Muncie, Herbert L; Phillips-Savoy, Amanda R

    2015-08-01

    Rosacea is a chronic facial skin condition of unknown cause. It is characterized by marked involvement of the central face with transient or persistent erythema, telangiectasia, inflammatory papules and pustules, or hyperplasia of the connective tissue. Transient erythema, or flushing, is often accompanied by a feeling of warmth. It usually lasts for less than five minutes and may spread to the neck and chest. Less common findings include erythematous plaques, scaling, edema, phymatous changes (thickening of skin due to hyperplasia of sebaceous glands), and ocular symptoms. The National Rosacea Society Expert Committee defines four subtypes of rosacea (erythematotelangiectatic, papulopustular, phymatous, and ocular) and one variant (granulomatous). Treatment starts with avoidance of triggers and use of mild cleansing agents and moisturizing regimens, as well as photoprotection with wide-brimmed hats and broad-spectrum sunscreens (minimum sun protection factor of 30). For inflammatory lesions and erythema, the recommended initial treatments are topical metronidazole or azelaic acid. Once-daily brimonidine, a topical alpha-adrenergic receptor agonist, is effective in reducing erythema. Papulopustular rosacea can be treated with systemic therapy including tetracyclines, most commonly subantimicrobial-dose doxycycline. Phymatous rosacea is treated primarily with laser or light-based therapies. Ocular rosacea is managed with lid hygiene, topical cyclosporine, and topical or systemic antibiotics.

  2. The association between clinical and radiographic periodontitis measurements during periodontal maintenance.

    Science.gov (United States)

    Payne, Jeffrey B; Nummikoski, Pirkka V; Thompson, David M; Golub, Lorne M; Stoner, Julie A

    2013-10-01

    The purpose of the present study is to examine the association between clinical and radiographic periodontitis measurements during 2 years of periodontal maintenance. Secondary analyses were performed from a 2-year, double-masked, placebo-controlled, randomized clinical trial evaluating the efficacy and safety of subantimicrobial dose doxycycline (SDD) in 128 postmenopausal osteopenic females with moderate-to-severe chronic periodontitis. Relative clinical attachment level (relative CAL) and probing depth (PD) measurements were made. Posterior vertical bitewings were taken for alveolar bone density (ABD) and alveolar bone height (ABH) measurements. Generalized estimating equations were used to model associations. One-year ABD changes and 1-year relative CAL/PD changes did not predict 2-year ABH changes and ABH/ABD changes, respectively. Baseline relative CAL and PD were positively associated with baseline ABH loss (P periodontal maintenance, baseline PD was associated with subsequent ABD and ABH loss. Although no longitudinal change preceded another measurement change, changes in PDs and relative CALs appeared to reflect changes in the underlying alveolar bone over time.

  3. Non-antibacterial tetracycline formulations: clinical applications in dentistry and medicine

    Directory of Open Access Journals (Sweden)

    Ying Gu

    2012-10-01

    Full Text Available In 1983, it was first reported that tetracyclines (TCs can modulate the host response, including (but not limited to inhibition of pathologic matrix metalloproteinase (MMP activity, and by mechanisms unrelated to the antibacterial properties of these drugs. Soon thereafter, strategies were developed to generate non-antibacterial formulations (subantimicrobial-dose doxycycline; SDD and compositions (chemically modified tetracyclines; CMTs of TCs as host-modulating drugs to treat periodontal and other inflammatory diseases. This review focuses on the history and rationale for the development of: (a SDD which led to two government-approved medications, one for periodontitis and the other for acne/rosacea and (b CMTs, which led to the identification of the active site of the drugs responsible for MMP inhibition and to studies demonstrating evidence of efficacy of the most potent of these, CMT-3, as an anti-angiogenesis agent in patients with the cancer, Kaposi's sarcoma, and as a potential treatment for a fatal lung disease (acute respiratory distress syndrome; ARDS. In addition, this review discusses a number of clinical studies, some up to 2 years’ duration, demonstrating evidence of safety and efficacy of SDD formulations in humans with oral inflammatory diseases (periodontitis, pemphigoid as well as medical diseases, including rheumatoid arthritis, post-menopausal osteopenia, type II diabetes, cardiovascular diseases, and a rare and fatal lung disease, lymphangioleiomyomatosis.

  4. Chitosan-doxycycline hydrogel: An MMP inhibitor/sclerosing embolizing agent as a new approach to endoleak prevention and treatment after endovascular aneurysm repair.

    Science.gov (United States)

    Zehtabi, Fatemeh; Ispas-Szabo, Pompilia; Djerir, Djahida; Sivakumaran, Lojan; Annabi, Borhane; Soulez, Gilles; Mateescu, Mircea Alexandru; Lerouge, Sophie

    2017-12-01

    The success of endovascular repair of abdominal aortic aneurysms remains limited due to the development of endoleaks. Sac embolization has been proposed to manage endoleaks, but current embolizing materials are associated with frequent recurrence. An injectable agent that combines vascular occlusion and sclerosing properties has demonstrated promise for the treatment of endoleaks. Moreover, the inhibition of aneurysmal wall degradation via matrix metalloproteinases (MMPs) may further prevent aneurysm progression. Thus, an embolization agent that promotes occlusion, MMP inhibition and endothelial ablation was hypothesized to provide a multi-faceted approach for endoleak treatment. In this study, an injectable, occlusive chitosan (CH) hydrogel containing doxycycline (DOX)-a sclerosant and MMP inhibitor-was developed. Several CH-DOX hydrogel formulations were characterized for their mechanical and sclerosing properties, injectability, DOX release rate, and MMP inhibition. An optimized formulation was assessed for its short-term ability to occlude blood vessels in vivo. All formulations were injectable and gelled rapidly at body temperature. Only hydrogels prepared with 0.075M sodium bicarbonate and 0.08M phosphate buffer as the gelling agent presented sufficient mechanical properties to immediately impede physiological flow. DOX release from this gel was in a two-stage pattern: a burst release followed by a slow continuous release. Released DOX was bioactive and able to inhibit MMP-2 activity in human glioblastoma cells. Preliminary in vivo testing in pig renal arteries showed immediate and delayed embolization success of 96% and 86%, respectively. Altogether, CH-DOX hydrogels appear to be promising new multifunctional embolic agents for the treatment of endoleaks. An injectable embolizing chitosan hydrogel releasing doxycycline (DOX) was developed as the first multi-faceted approach for the occlusion of blood vessels. It combines occlusive properties with DOX

  5. Short communication: Interaction of the isomers carvacrol and thymol with the antibiotics doxycycline and tilmicosin: In vitro effects against pathogenic bacteria commonly found in the respiratory tract of calves.

    Science.gov (United States)

    Kissels, W; Wu, X; Santos, R R

    2017-02-01

    Bovine respiratory disease is the major problem faced by cattle, specially calves, leading to reduced animal performance and increased mortality, consequently causing important economic losses. Hence, calves must be submitted to antibiotic therapy to counteract this infection usually initiated by the combination of environmental stress factors and viral infection, altering the animal's defense mechanism, and thus allowing lung colonization by the opportunistic bacteria Mannheimia haemolytica and Pasteurella multocida. Essential oils appear to be candidates to replace antibiotics or to act as antibiotic adjuvants due to their antimicrobial properties. In the present study, we aimed to evaluate the 4 essential oil components carvacrol, thymol, trans-anethole, and 1,8 cineole as antibacterial agents or as adjuvants for the antibiotics doxycycline and tilmicosin against M. haemolytica and P. multocida. Bacteria were cultured according to standard protocols, followed by the determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration. A checkerboard assay was applied to detect possible interactions between components, between antibiotics, and between components and antibiotics. Doxycycline at 0.25 and 0.125 μg/mL inhibited the growth of P. multocida and M. haemolytica, respectively, whereas tilmicosin MIC values were 1.0 and 4.0 μg/mL for P. multocida and M. haemolytica, respectively. Carvacrol MIC values were 2.5 and 1.25 mM for P. multocida and M. haemolytica, respectively, whereas thymol MIC values were 1.25 and 0.625 mM for P. multocida and M. haemolytica, respectively. Trans-anethole and 1,8 cineole did not present any antibacterial effect even at 40 mM against the investigated pathogens. All minimum bactericidal concentration values were the same as MIC, except when thymol was tested against M. haemolytica, being twice the MIC data (i.e., 1.25 mM thymol). Based on fractional inhibitory concentration checkerboard assay, no

  6. Pulp revascularization of replanted immature dog teeth after treatment with minocycline and doxycycline assessed by laser Doppler flowmetry, radiography, and histology.

    Science.gov (United States)

    Ritter, Alessandra Luisa de Souza; Ritter, André Vicente; Murrah, Valerie; Sigurdsson, Asgeir; Trope, Martin

    2004-04-01

    This study investigated the effect of topical antibiotic treatment on pulp revascularization in replanted teeth. Thirty-four immature teeth were selected from three young dogs. Baseline radiographs and laser Doppler flowmetry (LDF) readings were obtained. Specimens were randomly divided into four groups: Thirty-eight teeth were extracted, kept dry for 5 min, and either (Group 1) covered with minocycline mixture (G1, n = 11), (Group 2) soaked in doxycycline (G2, n = 11), or (Group 3) soaked in saline (G3-negative control, n = 6), and replanted. Teeth in Group 4 were not extracted (positive control, n = 6). Postoperative radiographs and LDF readings were obtained for 2 months after replantation. After sacrifice, the jaws were collected and processed for light microscopy. Pre- and postreplantation LDF readings and radiographs, and histologic findings were analyzed to assess revascularization. Pulp revascularization occurred in 91% (G1), 73% (G2), and 33% (G3) of the specimens. In conclusion, minocycline facilitates pulp revascularization in replanted immature teeth after replantation. Copyright Blackwell Munksgaard, 2004.

  7. The Development of a Viral Mediated CRISPR/Cas9 System with Doxycycline Dependent gRNA Expression for Inducible In vitro and In vivo Genome Editing.

    Science.gov (United States)

    de Solis, Christopher A; Ho, Anthony; Holehonnur, Roopashri; Ploski, Jonathan E

    2016-01-01

    The RNA-guided Cas9 nuclease, from the type II prokaryotic Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) adaptive immune system, has been adapted and utilized by scientists to edit the genomes of eukaryotic cells. Here, we report the development of a viral mediated CRISPR/Cas9 system that can be rendered inducible utilizing doxycycline (Dox) and can be delivered to cells in vitro and in vivo utilizing adeno-associated virus (AAV). Specifically, we developed an inducible gRNA (gRNAi) AAV vector that is designed to express the gRNA from a H1/TO promoter. This AAV vector is also designed to express the Tet repressor (TetR) to regulate the expression of the gRNAi in a Dox dependent manner. We show that H1/TO promoters of varying length and a U6/TO promoter can edit DNA with similar efficiency in vitro, in a Dox dependent manner. We also demonstrate that our inducible gRNAi vector can be used to edit the genomes of neurons in vivo within the mouse brain in a Dox dependent manner. Genome editing can be induced in vivo with this system by supplying animals Dox containing food for as little as 1 day. This system might be cross compatible with many existing S. pyogenes Cas9 systems (i.e., Cas9 mouse, CRISPRi, etc.), and therefore it likely can be used to render these systems inducible as well.

  8. The development of a viral mediated CRISPR/Cas9 system with doxycycline dependent gRNA expression for inducible in vitro and in vivo genome editing.

    Directory of Open Access Journals (Sweden)

    Christopher A. de Solis

    2016-08-01

    Full Text Available The RNA-guided Cas9 nuclease, from the type II prokaryotic Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR adaptive immune system, has been adapted and utilized by scientists to edit the genomes of eukaryotic cells. Here, we report the development of a viral mediated CRISPR/Cas9 system that can be rendered inducible utilizing doxycycline (Dox and can be delivered to cells in vitro and in vivo utilizing adeno-associated virus (AAV. Specifically, we developed an inducible gRNA (gRNAi AAV vector that is designed to express the gRNA from a H1/TO promoter. This AAV vector is also designed to express the Tet repressor (TetR to regulate the expression of the gRNAi in a Dox dependent manner. We show that H1/TO promoters of varying length and a U6/TO promoter can edit DNA with similar efficiency in vitro, in a Dox dependent manner. We also demonstrate that our inducible gRNAi vector can be used to edit the genomes of neurons in vivo within the mouse brain in a Dox dependent manner. Genome editing can be induced in vivo with this system by supplying animals Dox containing food for as little as one day. This system might be cross compatible with many existing S. pyogenes Cas9 systems (i.e. Cas9 mouse, CRISPRi, etc., and therefore it likely can be used to render these systems inducible as well.

  9. Is there a causal relationship between genetic changes and radiomics-based image features? An in vivo preclinical experiment with doxycycline inducible GADD34 tumor cells.

    Science.gov (United States)

    Panth, Kranthi Marella; Leijenaar, Ralph T H; Carvalho, Sara; Lieuwes, Natasja G; Yaromina, Ala; Dubois, Ludwig; Lambin, Philippe

    2015-09-01

    The central hypothesis of "radiomics" is that imaging features reflect tumor phenotype and genotype. Until now only correlative studies have been performed. The main objective of our study is to determine whether a causal relationship exists between genetic changes and image features. The secondary objective is to assess whether the combination with radiotherapy (RT) influences these image features. HCT116 doxycycline (dox) inducible GADD34 cells were grown as xenografts in the flanks of NMRI-nu mice. GADD34 overexpression decreases hypoxic fraction. Radiomics analyses were performed on computed tomography images obtained at 40kVp and again at 80kVp for validation, before radiotherapy at a volume of 200mm(3), 4days post RT (10Gy) and 500mm(3). To select reproducible features test-retest experiments were performed at baseline. Gene induction and/or irradiation translated into significant changes in radiomics features. Post irradiation, 17 features for 40kVp and 9 features for 80kVp differed significantly between dox+ and dox- combined with RT. 8 and 4 of these features remained consistent for 40 and 80kVp, respectively. Radiomics is able to identify early effects of changed gene expression combined with radiation treatment in tumors with similar volumes which are not visible to human eye. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  10. Variations in the fate and biological effects of sulfamethoxazole, norfloxacin and doxycycline in different vegetable-soil systems following manure application.

    Science.gov (United States)

    Wang, Jianmei; Lin, Hui; Sun, Wanchun; Xia, Yun; Ma, Junwei; Fu, Jianrong; Zhang, Zulin; Wu, Huizhen; Qian, Mingrong

    2016-03-05

    The fate of sulfamethoxazole (SMZ), norfloxacin (NOR) and doxycycline (DOX) and their biological effects in radish and pakchoi culture systems were investigated. DOX dissipated more rapidly than SMZ and NOR, while radish and pakchoi cultivation increased the removal of residual DOX in soils. Dissipation of NOR was accelerated in radish soils but was slowed down slightly in pakchoi soils. Vegetable cultivation exerted an insignificant effect on SMZ removal. Investigation of antibiotic bioaccumulation showed that the uptake of DOX by radish and pakchoi was undetectable, but the radish accumulated more SMZ and NOR than pakchoi. Among the three antibiotics, only SMZ use exhibited an apparent suspension of plant seed germination, up-ground plant growth and soil microbial diversity. Pakchoi responded more sensitively to SMZ than did the radish. Principal component analysis (PCA) based on MicroRESP™ indicated that the sampling time and antibiotic treatments could influence the soil microbial community. Only in the pakchoi soils did antibiotic application exert a more robust effect on the microbial community than the sampling time; SMZ treatments and DOX treatments could be clearly discriminated from the control treatments. These results are crucial for an assessment of the potential risks of antibiotics to culture system practices and suggest that good agricultural practices help to limit or even reduce antibiotic pollution. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. An environmental dose experiment

    Science.gov (United States)

    Peralta, Luis

    2017-11-01

    Several radiation sources worldwide contribute to the delivered dose to the human population. This radiation also acts as a natural background when detecting radiation, for instance from radioactive sources. In this work a medium-sized plastic scintillation detector is used to evaluate the dose delivered by natural radiation sources. Calibration of the detector involved the use of radioactive sources and Monte Carlo simulation of the energy deposition per disintegration. A measurement of the annual dose due to background radiation to the body was then estimated. A dose value compatible with the value reported by the United Nations Scientific Committee on the Effects of Atomic Radiation was obtained.

  12. Fertilizer micro-dosing

    International Development Research Centre (IDRC) Digital Library (Canada)

    millet, sorghum) under micro-dosing and water harvesting. • Farmers' access to fertilizer has been improved by an innovative 'warrantage' credit scheme, that has enabled over 1,000 farmers (30% women), to purchase and use more fertilizer on food crops. Fertilizer micro-dosing: a profitable innovation for. Sahelian women.

  13. Clozapine dose for schizophrenia.

    Science.gov (United States)

    Subramanian, Selvizhi; Völlm, Birgit A; Huband, Nick

    2017-06-14

    Schizophrenia and related disorders such as schizophreniform and schizoaffective disorder are serious mental illnesses characterised by profound disruptions in thinking and speech, emotional processes, behaviour and sense of self. Clozapine is useful in the treatment of schizophrenia and related disorders, particularly when other antipsychotic medications have failed. It improves positive symptoms (such as delusions and hallucinations) and negative symptoms (such as withdrawal and poverty of speech). However, it is unclear what dose of clozapine is most effective with the least side effects. To compare the efficacy and tolerability of clozapine at different doses and to identify the optimal dose of clozapine in the treatment of schizophrenia, schizophreniform and schizoaffective disorders. We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (August 2011 and 8 December 2016). All relevant randomised controlled trials (RCTs), irrespective of blinding status or language, that compared the effects of clozapine at different doses in people with schizophrenia and related disorders, diagnosed by any criteria. We independently inspected citations from the searches, identified relevant abstracts, obtained full articles of relevant abstracts, and classified trials as included or excluded. We included trials that met our inclusion criteria and reported useable data. For dichotomous data, we calculated the relative risk (RR) and the 95% confidence interval (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated mean differences (MD) again based on a random-effects model. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. We identified five studies that could be included. Each compared the effects of clozapine at very low dose (up to 149 mg/day), low dose (150 mg/day to 300 mg/day) and standard dose (301 mg/day to 600 mg/day). Four of the five included

  14. Doxycycline Protects Thymic Epithelial Cells from Mitomycin C-Mediated Apoptosis In Vitro via Trx2-NF-κB-Bcl-2/Bax Axis

    Directory of Open Access Journals (Sweden)

    Jun Wang

    2016-02-01

    Full Text Available Background/Aims: Age-associated and stress-induced involution of the thymus is accompanied by reduced numbers of thymic epithelial cells (TECs and severe reduction in peripheral T cell repertoire specificities. These events seriously affect immune function, but the mechanisms involved are unclear. Our preliminary findings showed that doxycycline (Dox could drive the proliferation of a TEC line (MTEC1 cells partially via the MAPK signaling pathway. Dox can also up-regulate IL-6 and GM-CSF expression via the NF-κB and MAPK/ERK pathways. Herein, we investigate the effects and mechanisms used by Dox that protect against mitomycin C (MMC-induced MTEC1 cell apoptosis. Methods: MTEC1 cells were treated with Dox, MMC, and Dox plus MMC for different amounts of time. The expression of Trx2, NF-κB, Bcl-2, and Bax proteins were then detected by western blotting. Results: Our findings show that Dox protects MTEC1 cells from MMC-induced apoptosis. Dox up-regulated the expression of Trx2 and promoted NF-κB phosphorylation. Meanwhile, Dox also increased the expression of Bcl-2, partially reduced the expression of Bax, and normalized the ratio of Bcl-2 to Bax. Conclusion: Dox exerts an anti-apoptosis function via the NF-κB-Bcl-2/Bax and Trx2-ASK1/JNK pathways in vitro. Therefore, Dox may represent a drug that could be used to attenuate thymic senescence, rescue thymic function, and promote T cell reconstitution.

  15. Reproducibility of parameter learning with missing observations in naive Wnt Bayesian network trained on colorectal cancer samples and doxycycline-treated cell lines.

    Science.gov (United States)

    Sinha, Shriprakash

    2015-07-01

    In this manuscript the reproducibility of parameter learning with missing observations in a naive Bayesian network and its effect on the prediction results for Wnt signaling activation in colorectal cancer is tested. The training of the network is carried out separately on doxycycline-treated LS174T cell lines (GSE18560) as well as normal and adenoma samples (GSE8671). A computational framework to test the reproducibility of the parameters is designed in order check the veracity of the prediction results. Detailed experimental analysis suggests that the prediction results are accurate and reproducible with negligible deviations. Anomalies in estimated parameters are accounted for due to the representation issues of the Bayesian network model. High prediction accuracies are reported for normal (N) and colon-related adenomas (AD), colorectal cancer (CRC), carcinomas (C), adenocarcinomas (ADC) and replication error colorectal cancer (RER CRC) test samples. Test samples from inflammatory bowel diseases (IBD) do not fare well in the prediction test. Also, an interesting case regarding hypothesis testing came up while proving the statistical significance of the different design setups of the Bayesian network model. It was found that hypothesis testing may not be the correct way to check the significance between design setups, especially when the structure of the model is the same, given that the model is trained on a single piece of test data. The significance test does have value when the datasets are independent. Finally, in comparison to the biologically inspired models, the naive Bayesian model may give accurate results, but this accuracy comes at the cost of a loss of crucial biological knowledge which might help reveal hidden relations among intra/extracellular factors affecting the Wnt pathway.

  16. Evaluation of the regenerative potential of 25% doxycycline-loaded biodegradable membrane vs biodegradable membrane alone in the treatment of human periodontal infrabony defects: A clinical and radiological study

    Directory of Open Access Journals (Sweden)

    Chaturvedi Rashi

    2008-01-01

    Full Text Available Background: Microbial colonization of the barrier membranes used for guided tissue regeneration is inevitable and can lead to delayed healing. Aims: Antimicrobial coating of the membrane with 25% doxycycline paste has been attempted to prevent infection and achieve enhanced regeneration in periodontal infrabony defects. Materials and Methods: Twenty-four patients with 2-walled or 3-walled infrabony defects were selected and randomly divided into two equal groups. Infrabony defects of group A were treated with a biodegradable membrane coated with 25% doxycycline while those of group B were treated with membrane alone. Clinical assessment of probing depth and attachment level and radiographic evaluation of the defect depth was done preoperatively and at 12 and 24 weeks postoperatively. Statistical Analysis: The relative efficacy of the two treatment modalities were evaluated using the paired Student′s t- test and the comparative evaluation between the two groups was done using the independent Student′s t -test. Results: Both the groups exhibited a highly significant reduction in probing depth and gain in clinical attachment level and linear bone fill at the end of 24 weeks. Comparative evaluation between the two study groups revealed a significant reduction in probing depth ( P = 0.016 FNx01 and linear bone fill ( P = 0.02 FNx01 in group A as compared to group B. Mean gain in attachment level was greater for group A than for group B but the difference was statistically nonsignificant ( P = 0.065 NS . Conclusions: The results suggest that doxycycline is beneficial in reducing membrane-associated infection and can potentiate regeneration through host modulation.

  17. Controllable dose; Dosis controlable

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez R, J.T.; Anaya M, R.A. [ININ, A.P. 18-1027, 11801 Mexico D.F. (Mexico)]. E-mail: jtar@nuclear.inin.mx

    2004-07-01

    With the purpose of eliminating the controversy about the lineal hypothesis without threshold which found the systems of dose limitation of the recommendations of ICRP 26 and 60, at the end of last decade R. Clarke president of the ICRP proposed the concept of Controllable Dose: as the dose or dose sum that an individual receives from a particular source which can be reasonably controllable by means of any means; said concept proposes a change in the philosophy of the radiological protection of its concern by social approaches to an individual focus. In this work a panorama of the foundations is presented, convenient and inconveniences that this proposal has loosened in the international community of the radiological protection, with the purpose of to familiarize to our Mexican community in radiological protection with these new concepts. (Author)

  18. Acetaminophen dosing for children

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000783.htm Acetaminophen dosing for children To use the sharing features ... much of this medicine can be harmful. How Acetaminophen Can Help Your Child Acetaminophen is used to ...

  19. Utirik Atoll Dose Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Robison, W.L.; Conrado, C.L.; Bogen, K.T

    1999-10-06

    On March 1, 1954, radioactive fallout from the nuclear test at Bikini Atoll code-named BRAVO was deposited on Utirik Atoll which lies about 187 km (300 miles) east of Bikini Atoll. The residents of Utirik were evacuated three days after the fallout started and returned to their atoll in May 1954. In this report we provide a final dose assessment for current conditions at the atoll based on extensive data generated from samples collected in 1993 and 1994. The estimated population average maximum annual effective dose using a diet including imported foods is 0.037 mSv y{sup -1} (3.7 mrem y{sup -1}). The 95% confidence limits are within a factor of three of their population average value. The population average integrated effective dose over 30-, 50-, and 70-y is 0.84 mSv (84, mrem), 1.2 mSv (120 mrem), and 1.4 mSv (140 mrem), respectively. The 95% confidence limits on the population-average value post 1998, i.e., the 30-, 50-, and 70-y integral doses, are within a factor of two of the mean value and are independent of time, t, for t > 5 y. Cesium-137 ({sup 137}Cs) is the radionuclide that contributes most of this dose, mostly through the terrestrial food chain and secondarily from external gamma exposure. The dose from weapons-related radionuclides is very low and of no consequence to the health of the population. The annual background doses in the U. S. and Europe are 3.0 mSv (300 mrem), and 2.4 mSv (240 mrem), respectively. The annual background dose in the Marshall Islands is estimated to be 1.4 mSv (140 mrem). The total estimated combined Marshall Islands background dose plus the weapons-related dose is about 1.5 mSv y{sup -1} (150 mrem y{sup -1}) which can be directly compared to the annual background effective dose of 3.0 mSv y{sup -1} (300 mrem y{sup -1}) for the U. S. and 2.4 mSv y{sup -1} (240 mrem y{sup -1}) for Europe. Moreover, the doses listed in this report are based only on the radiological decay of {sup 137}Cs (30.1 y half-life) and other

  20. Argatroban dosing in obesity.

    Science.gov (United States)

    Elagizi, Stephanie; Davis, Kyle

    2018-01-09

    Obesity is associated with significant alterations in pharmacokinetic and pharmacodynamic properties. The use of weight based anticoagulants such as argatroban may put obese patients at an increased risk of hemorrhagic events. The purpose of this study was to evaluate argatroban dosing requirements in obese vs non-obese patients. This single-center, retrospective cohort study included patients ≥18 years with suspected HIT, treated with argatroban for ≥12 h. Patients were stratified by body mass index (BMI) into obese (BMI > 30 kg/m2) and non-obese (BMI ≤ 30 kg/m2) groups. The primary outcome was the median maintenance dose required to achieve two consecutive therapeutic activated partial thromboplastin times. A total of 121 patients were included. The median BMI in the obese vs non-obese groups was 35.8 vs 24.05 kg/m2 (p < .0001). Although statistically significant, there was no clinically significant difference in median maintenance argatroban dose in obese versus non-obese patients (1 vs 1 μg/kg/min; p = .01). In-hospital major bleeding and in-hospital thrombosis also did not differ between the two groups. Obese patients require similar median argatroban maintenance doses when compared to non-obese patients. Based on these results argatroban should be dosed using actual body weight regardless of BMI. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Assessment of internal doses

    CERN Document Server

    Rahola, T; Falk, R; Isaksson, M; Skuterud, L

    2002-01-01

    There is a definite need for training in dose calculation. Our first course was successful and was followed by a second, both courses were fully booked. An example of new tools for software products for bioassay analysis and internal dose assessment is the Integrated Modules for Bioassay Analysis (IMBA) were demonstrated at the second course. This suite of quality assured code modules have been adopted in the UK as the standard for regulatory assessment purposes. The intercomparison measurements are an important part of the Quality Assurance work. In what is known as the sup O utside workers ' directive it is stated that the internal dose measurements shall be included in the European Unions supervision system for radiation protection. The emergency preparedness regarding internal contamination was much improved by the training with and calibration of handheld instruments from participants' laboratories. More improvement will be gained with the handbook giving practical instructions on what to do in case of e...

  2. Doses of Tktazzus Tbxoid '

    African Journals Online (AJOL)

    Summary. Famnde O], Familusi ]B. Post—neonatal Tetanus in Nigeria: A Need for Booster. Doses of Tetanus Toxoid. 1V1_'gen'an journal ofPaediatn'cs 2001; 28:35. Eighty-two (87 per cent) of the 94- cases of post-neonatal tetanus patients seen in the department of paediatrics,. University College Hospital, Ibadan, over an ...

  3. Ibuprofen dosing for children

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000772.htm Ibuprofen dosing for children To use the sharing features on this page, ... much of this medicine can be harmful. How Ibuprofen can Help Your Child Ibuprofen is a type of nonsteroidal anti-inflammatory ...

  4. Biological dose estimation

    African Journals Online (AJOL)

    to this effect was found in at least 3 cases using biological dosimetric criteria, proving the ... The classification system described by Savage3 was used to determine the ... TABLE I. DISTANCE FROM RADIATION SOURCE, DETAILS OF CYTOGENETIC ANALYSIS AND BIOLOGICAL AND PHYSICAL. DOSE ESTIMATIONS.

  5. Dose Reduction Techniques

    CERN Document Server

    Waggoner, L O

    2000-01-01

    As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the sm...

  6. Dose specification for radiation therapy: dose to water or dose to medium?

    Science.gov (United States)

    Ma, C.-M.; Li, Jinsheng

    2011-05-01

    The Monte Carlo method enables accurate dose calculation for radiation therapy treatment planning and has been implemented in some commercial treatment planning systems. Unlike conventional dose calculation algorithms that provide patient dose information in terms of dose to water with variable electron density, the Monte Carlo method calculates the energy deposition in different media and expresses dose to a medium. This paper discusses the differences in dose calculated using water with different electron densities and that calculated for different biological media and the clinical issues on dose specification including dose prescription and plan evaluation using dose to water and dose to medium. We will demonstrate that conventional photon dose calculation algorithms compute doses similar to those simulated by Monte Carlo using water with different electron densities, which are close (doses to media but significantly different (up to 11%) from doses to water converted from doses to media following American Association of Physicists in Medicine (AAPM) Task Group 105 recommendations. Our results suggest that for consistency with previous radiation therapy experience Monte Carlo photon algorithms report dose to medium for radiotherapy dose prescription, treatment plan evaluation and treatment outcome analysis.

  7. Survey on immunotherapy practice patterns: dose, dose adjustments, and duration.

    Science.gov (United States)

    Larenas-Linnemann, Désirée E S; Gupta, Payel; Mithani, Sima; Ponda, Punita

    2012-05-01

    Practical issues dealing with the administration of allergen immunotherapy (AIT) by European and US allergists are not well known. Several concerns are only partially covered by guidelines. To survey AIT practice patterns among worldwide members of the American Academy of Allergy, Asthma and Immunology (AAAAI). A web-based survey was conducted among AAAAI members on dosing, dose adjustment after missed doses, and duration of AIT. A total of 1,201 replies (24.7% response rate of which 10% of responses were from non-US and non-Canada members). A total of 57% to 65% of the US-Canadian dosing falls within the recommended Practice Parameter ranges (9.4%-19% too low). Dose adjustment after missed doses is based on time elapsed since the last administered dose by 77% of US-Canadian and 58% of non-US-Canadian allergists. Doses are reduced when a patient comes in more than 14 days for 5 weeks after the last administration and initial dosing restarted after more than 30 days for 12 weeks since last administration during the build-up or maintenance stage. After missing 1 to 3 doses, the dosing schedules were mostly followed (build-up phase: repeat last dose, reduce by 1 dose, reduce by 2doses; maintenance phase: reduce by 1 dose, reduce by 2 doses, reduce by 3 doses). AIT is prescribed for a median of 3 years by non-US-Canadian allergists but for a median of 5 years by 75% of US-Canadian allergists. Main reasons for continuing beyond 5 years were "after stopping, symptoms reappeared" or "patient afraid to relapse." Many patients receive less than recommended doses. Two areas in which to plan further research are establishment of an optimal dose-adjustment plan for missed applications and exploration of the maximum appropriate duration of immunotherapy. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. Entrance surface dose according to dose calculation: Head and wrist

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Ho Jin [Dept. Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of); Han, Jae Bok; Song, Jong Nam; Choi, Nam Gil [Dept. of Radiological Science, Dongshin University, Naju (Korea, Republic of)

    2016-09-15

    This study were compared with the direct measurement and indirect dose methods through various dose calculation in head and wrist. And, the modified equation was proposed considering equipment type, setting conditions, tube voltage, inherent filter, added filter and its accompanied back scatter factor. As a result, it decreased the error of the direct measurement than the existing dose calculation. Accordingly, diagnostic radiography patient dose comparison would become easier and radiographic exposure control and evaluation will become more efficient. The study findings are expected to be useful in patients' effective dose rate evaluation and dose reduction.

  9. Doses from radiation exposure

    CERN Document Server

    Menzel, H G

    2012-01-01

    Practical implementation of the International Commission on Radiological Protection's (ICRP) system of protection requires the availability of appropriate methods and data. The work of Committee 2 is concerned with the development of reference data and methods for the assessment of internal and external radiation exposure of workers and members of the public. This involves the development of reference biokinetic and dosimetric models, reference anatomical models of the human body, and reference anatomical and physiological data. Following ICRP's 2007 Recommendations, Committee 2 has focused on the provision of new reference dose coefficients for external and internal exposure. As well as specifying changes to the radiation and tissue weighting factors used in the calculation of protection quantities, the 2007 Recommendations introduced the use of reference anatomical phantoms based on medical imaging data, requiring explicit sex averaging of male and female organ-equivalent doses in the calculation of effecti...

  10. Small dose... big poison.

    Science.gov (United States)

    Braitberg, George; Oakley, Ed

    2010-11-01

    It is not possible to identify all toxic substances in a single journal article. However, there are some exposures that in small doses are potentially fatal. Many of these exposures are particularly toxic to children. Using data from poison control centres, it is possible to recognise this group of exposures. This article provides information to assist the general practitioner to identify potential toxic substance exposures in children. In this article the authors report the signs and symptoms of toxic exposures and identify the time of onset. Where clear recommendations on the period of observation and known fatal dose are available, these are provided. We do not discuss management or disposition, and advise readers to contact the Poison Information Service or a toxicologist for this advice.

  11. First dose in man

    DEFF Research Database (Denmark)

    Hougaard Christensen, Mette Marie

    2011-01-01

    Du er blevet ansat som læge i et lægemiddelfirma med ansvar for planlægning og sikkerhed i fase 1 forsøg. Firmaet har udviklet tre dopamin D2-receptor antagonister til behandling af skizofreni. Lægemidlerne har undergået et omfattende farmakologisk, toksikologisk og farmaceutisk afprøvningsprogra...... fase 1 forsøg alias »First dose in man«....

  12. Short Course, High Dose Rifampicin Achieves Wolbachia Depletion Predictive of Curative Outcomes in Preclinical Models of Lymphatic\\ud Filariasis and Onchocerciasis

    OpenAIRE

    Aljayyoussi, Ghaith; Tyrer, Hayley; Ford, Louise; Sjoberg, Hanna; Pionnier, Nicolas; Waterhouse, David; Davies, Jill; Gamble, Joanne; Metugene, Haelly; Cook, Darren A. N.; Steven, Andrew; Sharma, Raman; Guimaraes, Ana F.; Clare, Rachel H.; Cassidy, Andrew

    2017-01-01

    Lymphatic filariasis (LF) and onchocerciasis are priority neglected tropical diseases targeted for elimination. The only safe drug treatment with substantial curative activity against the filarial nematodes responsible for LF (Brugia malayi, Wuchereria bancrofti) or onchocerciasis (Onchocerca volvulus) is doxycycline. The target of doxycycline is the essential endosymbiont, Wolbachia. Four to six weeks doxycycline therapy achieves >90% depletion of Wolbachia in worm tissues leading to blockad...

  13. Transit dose calculation in high dose rate brachytherapy (HDR ...

    African Journals Online (AJOL)

    Transit doses around a high dose rate 192Ir brachytherapy source were calculated using Sievert Integral at positions where the moving source was located exactly between two adjacent dwell positions. The correspond-ing transit dose rates were obtained by using energy absorption coefficients. Discrete step sizes of 0.25 ...

  14. Comparison of Safety and Efficacy of Oral Azithromycin-Topical Adapalene Versus Oral Doxycycline-Topical Adapalene in the Treatment of Acne Vulgaris and Determination of the Effects of These Treatments on Patients’ Quality of Life

    Directory of Open Access Journals (Sweden)

    Serap Kayhan

    2012-09-01

    Full Text Available Background and Design: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. Oral antibiotics and topical retinoids are effective in the treatment of acne.Materials and Methods: In this study, 60 patients with moderate acne vulgaris were evaluated; the patients were randomized into two equal groups. The groups were matched with respect to age, gender and clinical severity of acne. The patients in group 1 received oral azithromycin (500 mg daily on 3 consecutive days per week and the patients in group 2 received doxycycline (100 mg daily for 12 weeks. Topical adapalene gel was added to the systemic treatment in both groups. Clinical evaluation was performed at baseline and at the end of first, second and third months. Side effects were recorded. Quality of life in patients was measured with Skindex-29 and Acne Quality of Life Scale before treatment and at the end of third month. Results: At the end of the treatment, the patients in the two treatment groups had clinical improvement of more than 50%. Twenty-one patients in the azithromycin-adapalene group and 23 patients in the doxycycline-adapelene group had more than 80% clinical improvement. There was not any statistically significant difference in the clinical efficacy between the two combinations. Both treatment regimens were safe with minimal side effects. There was statistically significant difference in Skindex-29 and Acne Quality of Life Scale scores at baseline and at the end of the treatment (p0.05. Conclusion: Both treatments were efficient and safe. There was significant improvement in quality of life scale scores in both groups.

  15. The Effect of Systemic Delivery of Aminoguanidine versus Doxycycline on the Resorptive Phase of Alveolar Bone Following modified Widman Flap in Diabetic Rats: A Histopathological and Scanning Electron Microscope (SEM) study

    Science.gov (United States)

    Tella, E; Aldahlawi, S; Eldeeb, A; El Gazaerly, H

    2014-01-01

    Objectives Aminoguanidine (guanylhydrazinehydrochloride) is a drug that prevents many of the classical systemic complications of diabetes including diabetic osteopenia through its inhibitory activity on the accumulation of advanced glycation end –products (AGEs). The aim of the present study was to evaluate the effectiveness of aminoguanidine versus doxycycline in reducing alveolar bone resorption following mucoperiosteal flap in diabetic rats, using the conventional histopathology and scanning electron microscope (SEM). Methods Twenty-seven male albino rats were used in this study. Periodontal defects were induced experimentally on lower anterior teeth. All rats were subjected to induction of diabetes, by IV injection of the pancreatic B-cells toxin alloxan monohydrate. After eight weeks following the establishment of periodontal defects in all rats, the ligation was removed and 3 rats were scarified as negative control (group 1). The remaining animals were divided into three group based on treatment applied following mucoperiosteal flap surgery. Group 2 received saline treatment only, group 3 received doxycycline periostat (1.5 mg/kg/day) for 3 weeks, and group 4 received aminoguanidine (7.3 mmol/kg) for 3 weeks. The fasting glucose level was measured weekly post operatively. After 21 days all rats were sacrificed. Three anterior parts of the mandible of each group was prepared for histopathological examination and two parts were prepared for SEM. Results Aminoguanidine treated group (group 4) showed statistically significant increased new bone formation, higher number of osteoblasts and decrease osteoclasts number, resorptive lacunae and existing inflammatory cell infiltration as compared to positive control group (group 2) (Pdocumental by histopathological study. Conclusion The present study showed that aminoguanidine was significantly effective in reducing alveolar bone loss and can modify the detrimental effects of diabetes in alveolar bone resorption. PMID

  16. Peritoneal Dialysis Dose and Adequacy

    Science.gov (United States)

    ... Navigation Peritoneal Dialysis Peritoneal Dialysis: Dose & Adequacy Peritoneal Dialysis: Dose & Adequacy When kidneys fail, waste products such ... absorbed from the abdominal cavity. Types of Peritoneal Dialysis The two types of peritoneal dialysis differ mainly ...

  17. Hanford Environmental Dose Reconstruction Project

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, S.D.; Finch, S.M. (comps.)

    1992-10-01

    The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The independent Technical Steering Panel (TSP) provides technical direction. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates):Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates.

  18. Dose determination in high dose-rate brachytherapy.

    Science.gov (United States)

    Houdek, P V; Schwade, J G; Wu, X; Pisciotta, V; Fiedler, J A; Serago, C F; Markoe, A M; Abitbol, A A; Lewin, A A; Braunschweiger, P G

    1992-01-01

    Although high dose-rate brachytherapy with a single, rapidly moving radiation source is becoming a common treatment modality, a suitable formalism for determination of the dose delivered by a moving radiation source has not yet been developed. At present, brachytherapy software simulates high dose-rate treatments using only a series of stationary sources, and consequently fails to account for the dose component delivered while the source is in motion. We now describe a practical model for determination of the true, total dose administered. The algorithm calculates both the dose delivered while the source is in motion within and outside of the implanted volume (dynamic component), and the dose delivered while the source is stationary at a series of fixed dwell points. It is shown that the dynamic dose element cannot be ignored because it always increases the dose at the prescription points and, in addition, distorts the dose distribution within and outside of the irradiated volume. Failure to account for the dynamic dose component results in dosimetric errors that range from significant (> 10%) to negligible (source activity, and source speed as defined by the implant geometry.

  19. Solute clearance in CRRT: prescribed dose versus actual delivered dose.

    Science.gov (United States)

    Lyndon, William D; Wille, Keith M; Tolwani, Ashita J

    2012-03-01

    Substantial efforts have been made toward defining the dose threshold of continuous renal replacement therapy (CRRT) associated with improved survival in critically ill patients with acute kidney injury. Published studies have used prescribed effluent rates, expressed as total effluent volume (TEV) per weight and unit time (mL/kg/h), as a surrogate for dose. The purpose of this study was to compare differences in CRRT dose based on prescribed effluent rate, measured TEV and direct measurement of urea and creatinine clearance. We analyzed data that had been prospectively collected on 200 patients enrolled in a randomized trial comparing survival with a prescribed effluent rate of 20 mL/kg/h (standard dose) to 35 mL/kg/h (high dose) using pre-dilution continuous venovenous hemodiafiltration (CVVHDF). Filters were changed every 72 h. Blood urea nitrogen (BUN), serum creatinine (SCr), effluent urea nitrogen (EUN) and effluent creatinine (ECr) were collected daily. Actual delivered dose was calculated as: (EUN/BUN)*TEV for urea and (ECr/SCr)*TEV for creatinine. Data were available for 165 patients. In both groups, prescribed dose differed significantly from the measured TEV dose (P < 0.001). In the standard dose group, there was no difference between the measured TEV dose and actual delivered urea and creatinine clearances. However, in the high-dose group, measured TEV dose differed significantly from delivered urea clearance by 7.1% (P < 0.001) and creatinine clearance by 13.9% (P < 0.001). Dose based on prescribed effluent rate or measured TEV is a poor substitute for actual CVVHDF creatinine and urea clearance.

  20. Personalized exercise dose prescription.

    Science.gov (United States)

    Zubin Maslov, Petra; Schulman, Alexa; Lavie, Carl J; Narula, Jagat

    2017-12-28

    Physical activity (PA) is associated with increased longevity and decreased risk of cardiovascular disease, however, the majority of the general population is still sedentary. In order to maximize the health benefits of PA, health care practitioners should be familiarized with the appropriate dose of exercise for each healthy individual, depending on their habitual PA and relative fitness. The aim of this review is to quantitatively describe the lowest and the highest level of exercise that has health benefits, and what should hypothetically be considered 'the sweet spot'. Analysis of the current literature allows us to develop personalized 'exercise prescription' for healthy individuals. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2017. For permissions, please email: journals.permissions@oup.com.

  1. Experimental evaluation of neutron dose in radiotherapy patients: Which dose?

    Energy Technology Data Exchange (ETDEWEB)

    Romero-Expósito, M., E-mail: mariateresa.romero@uab.cat; Domingo, C.; Ortega-Gelabert, O.; Gallego, S. [Grup de Recerca en Radiacions Ionizants (GRRI), Departament de Física, Universitat Autònoma de Barcelona, Bellaterra 08193 (Spain); Sánchez-Doblado, F. [Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla 41009 (Spain); Servicio de Radiofísica, Hospital Universitario Virgen Macarena, Sevilla 41009 (Spain)

    2016-01-15

    Purpose: The evaluation of peripheral dose has become a relevant issue recently, in particular, the contribution of secondary neutrons. However, after the revision of the Recommendations of the International Commission on Radiological Protection, there has been a lack of experimental procedure for its evaluation. Specifically, the problem comes from the replacement of organ dose equivalent by the organ-equivalent dose, being the latter “immeasurable” by definition. Therefore, dose equivalent has to be still used although it needs the calculation of the radiation quality factor Q, which depends on the unrestricted linear energy transfer, for the specific neutron irradiation conditions. On the other hand, equivalent dose is computed through the radiation weighting factor w{sub R}, which can be easily calculated using the continuous function provided by the recommendations. The aim of the paper is to compare the dose equivalent evaluated following the definition, that is, using Q, with the values obtained by replacing the quality factor with w{sub R}. Methods: Dose equivalents were estimated in selected points inside a phantom. Two types of medical environments were chosen for the irradiations: a photon- and a proton-therapy facility. For the estimation of dose equivalent, a poly-allyl-diglicol-carbonate-based neutron dosimeter was used for neutron fluence measurements and, additionally, Monte Carlo simulations were performed to obtain the energy spectrum of the fluence in each point. Results: The main contribution to dose equivalent comes from neutrons with energy higher than 0.1 MeV, even when they represent the smallest contribution in fluence. For this range of energy, the radiation quality factor and the radiation weighting factor are approximately equal. Then, dose equivalents evaluated using both factors are compatible, with differences below 12%. Conclusions: Quality factor can be replaced by the radiation weighting factor in the evaluation of dose

  2. Organ Doses and Effective Doses in Pediatric Radiography: Patient-Dose Survey in Finland

    Energy Technology Data Exchange (ETDEWEB)

    Kiljunen, T.; Tietaevaeinen, A.; Parviainen, T.; Viitala, A.; Kortesniemi, M. (Radiation Practices Regulation, Radiation and Nuclear Safety Authority, Helsinki (Finland))

    2009-01-15

    Background: Use of the effective dose in diagnostic radiology permits the radiation exposure of diverse diagnostic procedures to be quantified. Fundamental knowledge of patient doses enhances the implementation of the 'as low as reasonably achievable' (ALARA) principle. Purpose: To provide comparative information on pediatric examination protocols and patient doses in skull, sinus, chest, abdominal, and pelvic radiography examinations. Material and Methods: 24 Finnish hospitals were asked to register pediatric examination data, including patient information and examination parameters and specifications. The total number of examinations in the study was 1916 (1426 chest, 228 sinus, 96 abdominal, 94 skull, and 72 pelvic examinations). Entrance surface dose (ESD) and dose-area products (DAP) were calculated retrospectively or DAP meters were used. Organ doses and effective doses were determined using a Monte Carlo program (PCXMC). Results: There was considerable variation in examination protocols between different hospitals, indicating large variations in patient doses. Mean effective doses of different age groups ranged from 5 muSv to 14 muSv in skull and sinus examinations, from 25 muSv to 483 muSv in abdominal examinations, and from 6 muSv to 48 muSv in chest examinations. Conclusion: In chest and sinus examinations, the amount of data was extensive, allowing national pediatric diagnostic reference levels to be defined. Parameter selection in pediatric examination protocols should be harmonized in order to reduce patient doses and improve optimization

  3. Hanford Environmental Dose Reconstruction Project

    Energy Technology Data Exchange (ETDEWEB)

    Finch, S.M.; McMakin, A.H. (comps.)

    1992-06-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is being managed and conducted by the Battelle Pacific Northwest Laboratories under contract with the Centers for Disease Control. The independent Technical Steering Panel (TSP) provides technical direction. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): source terms; environmental transport; environmental monitoring data; demography, food consumption, and agriculture; environmental pathways and dose estimates.

  4. REMEDIATION FACILITY WORKER DOSE ASSESSMENT

    Energy Technology Data Exchange (ETDEWEB)

    V. Arakali; E. Faillace

    2004-02-27

    The purpose of this design calculation is to estimate radiation doses received by personnel in the Remediation Facility performing operations to receive, prepare, open, repair, recover, disposition, and correct off-normal and non-standard conditions with casks, canisters, spent nuclear fuel (SNF) assemblies, and waste packages (WP). The specific scope of work contained in this calculation covers both collective doses and individual worker group doses on an annual basis, and includes the contributions due to external and internal radiation. The results of this calculation will be used to support the design of the Remediation Facility and provide occupational dose estimates for the License Application.

  5. Do dose area product meter measurements reflect radiation doses ...

    African Journals Online (AJOL)

    Enrique

    between radiation doses absorbed by health care workers and dose area product meter (DAP) measurements at Universitas Hospital, Bloemfontein. The DAP is an instrument which accurately measures the radiation emitted from the source. The study included the interventional radiolo- gists, radiographers and nurses ...

  6. Doxiciclina em pacientes com linfangioleiomiomatose: segurança e eficácia no bloqueio de metaloproteinases Doxycycline use in patients with lymphangioleiomyomatosis: safety and efficacy in metalloproteinase blockade

    Directory of Open Access Journals (Sweden)

    Suzana Pinheiro Pimenta

    2011-08-01

    Full Text Available OBJETIVO: A linfangioleiomiomatose (LAM é caracterizada pela presença de cistos pulmonares, cuja formação está associada à hiperreatividade de metaloproteinases de matriz (MMP, principalmente MMP-2 e MMP-9. Objetivamos comparar os níveis dessas MMPs entre pacientes com LAM e controles saudáveis, assim como avaliar, nas pacientes com LAM, a segurança e a eficácia do tratamento com doxiciclina, um potente inibidor de MMPs. MÉTODOS: Estudo clínico prospectivo no qual as pacientes com LAM receberam doxiciclina (100 mg/dia por seis meses, coletando-se amostras de urina e sangue para a dosagem de MMP-2 e MMP-9 antes e ao final do período. Foram ainda obtidas amostras de 10 mulheres saudáveis. RESULTADOS: De 41 pacientes com LAM que iniciaram o tratamento, 34 concluíram o protocolo. Os níveis de MMP-9 sérica e urinária foram significativamente inferiores no grupo controle (p OBJECTIVE: Lymphangioleiomyomatosis (LAM is characterized by lung cysts, whose development is associated with matrix metalloproteinase (MMP hyperactivity, principally that of MMP-2 and MMP-9. Our objective was to compare LAM patients and controls in terms of the levels of these MMPs, as well as to determine the safety and efficacy of treatment with doxycycline, a potent MMP inhibitor. METHODS: Prospective clinical study involving female LAM patients who received doxycycline (100 mg/day for six months. Urine and blood samples were collected for the quantification of MMP-2 and MMP-9 before and after the treatment period. Samples from 10 healthy women were also collected. RESULTS:Of the 41 LAM patients who started the treatment, 34 completed the protocol. Serum and urinary MMP-9 levels were significantly lower in the controls than in the LAM patients (p < 0.0001. Comparing pre- and post-treatment values, we found that the median level of MMP-9 in serum decreased from 919 ng/mL to 871 ng/mL (p = 0.05, whereas that of MMP-9 in urine decreased from 11,558 pg/mL to 7

  7. A dose error evaluation study for 4D dose calculations

    Science.gov (United States)

    Milz, Stefan; Wilkens, Jan J.; Ullrich, Wolfgang

    2014-10-01

    Previous studies have shown that respiration induced motion is not negligible for Stereotactic Body Radiation Therapy. The intrafractional breathing induced motion influences the delivered dose distribution on the underlying patient geometry such as the lung or the abdomen. If a static geometry is used, a planning process for these indications does not represent the entire dynamic process. The quality of a full 4D dose calculation approach depends on the dose coordinate transformation process between deformable geometries. This article provides an evaluation study that introduces an advanced method to verify the quality of numerical dose transformation generated by four different algorithms. The used transformation metric value is based on the deviation of the dose mass histogram (DMH) and the mean dose throughout dose transformation. The study compares the results of four algorithms. In general, two elementary approaches are used: dose mapping and energy transformation. Dose interpolation (DIM) and an advanced concept, so called divergent dose mapping model (dDMM), are used for dose mapping. The algorithms are compared to the basic energy transformation model (bETM) and the energy mass congruent mapping (EMCM). For evaluation 900 small sample regions of interest (ROI) are generated inside an exemplary lung geometry (4DCT). A homogeneous fluence distribution is assumed for dose calculation inside the ROIs. The dose transformations are performed with the four different algorithms. The study investigates the DMH-metric and the mean dose metric for different scenarios (voxel sizes: 8 mm, 4 mm, 2 mm, 1 mm 9 different breathing phases). dDMM achieves the best transformation accuracy in all measured test cases with 3-5% lower errors than the other models. The results of dDMM are reasonable and most efficient in this study, although the model is simple and easy to implement. The EMCM model also achieved suitable results, but the approach requires a more complex

  8. EPA's Benchmark Dose Modeling Software

    Science.gov (United States)

    The EPA developed the Benchmark Dose Software (BMDS) as a tool to help Agency risk assessors facilitate applying benchmark dose (BMD) method’s to EPA’s human health risk assessment (HHRA) documents. The application of BMD methods overcomes many well know limitations ...

  9. Dose calculation of anticancer drugs

    NARCIS (Netherlands)

    Gao, Bo; Klumpen, Heinz-Josef; Gurney, Howard

    2008-01-01

    BACKGROUND: Anticancer drugs are characterized by a narrow therapeutic window and significant inter-patient variability in therapeutic and toxic effects. Current body surface area (BSA)-based dosing fails to standardize systemic anticancer drug exposure and other alternative dosing strategies also

  10. Evolution of radon dose evaluation

    Directory of Open Access Journals (Sweden)

    Fujimoto Kenzo

    2004-01-01

    Full Text Available The historical change of radon dose evaluation is reviewed based on the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR reports. Since 1955, radon has been recognized as one of the important sources of exposure of the general public. However, it was not really understood that radon is the largest dose contributor until 1977 when a new concept of effective dose equivalent was introduced by International Commission on Radiological Protection. In 1982, the dose concept was also adapted by UNSCEAR and evaluated per caput dose from natural radiation. Many researches have been carried out since then. However, lots of questions have remained open in radon problems, such as the radiation weighting factor of 20 for alpha rays and the large discrepancy of risk estimation among dosimetric and epidemiological approaches.

  11. Radiation dose estimates for radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Stabin, M.G.; Stubbs, J.B.; Toohey, R.E. [Oak Ridge Inst. of Science and Education, TN (United States). Radiation Internal Dose Information Center

    1996-04-01

    Tables of radiation dose estimates based on the Cristy-Eckerman adult male phantom are provided for a number of radiopharmaceuticals commonly used in nuclear medicine. Radiation dose estimates are listed for all major source organs, and several other organs of interest. The dose estimates were calculated using the MIRD Technique as implemented in the MIRDOSE3 computer code, developed by the Oak Ridge Institute for Science and Education, Radiation Internal Dose Information Center. In this code, residence times for source organs are used with decay data from the MIRD Radionuclide Data and Decay Schemes to produce estimates of radiation dose to organs of standardized phantoms representing individuals of different ages. The adult male phantom of the Cristy-Eckerman phantom series is different from the MIRD 5, or Reference Man phantom in several aspects, the most important of which is the difference in the masses and absorbed fractions for the active (red) marrow. The absorbed fractions for flow energy photons striking the marrow are also different. Other minor differences exist, but are not likely to significantly affect dose estimates calculated with the two phantoms. Assumptions which support each of the dose estimates appears at the bottom of the table of estimates for a given radiopharmaceutical. In most cases, the model kinetics or organ residence times are explicitly given. The results presented here can easily be extended to include other radiopharmaceuticals or phantoms.

  12. Doxycycline-regulated 3T3-L1 preadipocyte cell line with inducible, stable expression of adenoviral E4orf1 gene: a cell model to study insulin-independent glucose disposal.

    Directory of Open Access Journals (Sweden)

    Rashmi Krishnapuram

    Full Text Available Impaired glycemic control and excessive adiposity are major risk factors for Type 2 Diabetes mellitus. In rodent models, Ad36, a human adenovirus, improves glycemic control, independent of dietary fat intake or adiposity. It is impractical to use Ad36 for therapeutic action. Instead, we identified that E4orf1 protein of Ad36, mediates its anti-hyperglycemic action independent of insulin signaling. To further evaluate the therapeutic potential of E4orf1 to improve glycemic control, we established a stable 3T3-L1 cell system in which E4orf1 expression can be regulated. The development and characterization of this cell line is described here. Full-length adenoviral-36 E4orf1 cDNA obtained by PCR was cloned into a tetracycline responsive element containing vector (pTRE-Tight-E4orf1. Upon screening dozens of pTRE-Tight-E4orf1 clones, we identified the one with the highest expression of E4orf1 in response to doxycycline treatment. Furthermore, using this inducible system we characterized the ability of E4orf1 to improve glucose disposal in a time dependent manner. This stable cell line offers a valuable resource to carefully study the novel signaling pathways E4orf1 uses to enhance cellular glucose disposal independent of insulin.

  13. Superficial dose evaluation of four dose calculation algorithms

    Science.gov (United States)

    Cao, Ying; Yang, Xiaoyu; Yang, Zhen; Qiu, Xiaoping; Lv, Zhiping; Lei, Mingjun; Liu, Gui; Zhang, Zijian; Hu, Yongmei

    2017-08-01

    Accurate superficial dose calculation is of major importance because of the skin toxicity in radiotherapy, especially within the initial 2 mm depth being considered more clinically relevant. The aim of this study is to evaluate superficial dose calculation accuracy of four commonly used algorithms in commercially available treatment planning systems (TPS) by Monte Carlo (MC) simulation and film measurements. The superficial dose in a simple geometrical phantom with size of 30 cm×30 cm×30 cm was calculated by PBC (Pencil Beam Convolution), AAA (Analytical Anisotropic Algorithm), AXB (Acuros XB) in Eclipse system and CCC (Collapsed Cone Convolution) in Raystation system under the conditions of source to surface distance (SSD) of 100 cm and field size (FS) of 10×10 cm2. EGSnrc (BEAMnrc/DOSXYZnrc) program was performed to simulate the central axis dose distribution of Varian Trilogy accelerator, combined with measurements of superficial dose distribution by an extrapolation method of multilayer radiochromic films, to estimate the dose calculation accuracy of four algorithms in the superficial region which was recommended in detail by the ICRU (International Commission on Radiation Units and Measurement) and the ICRP (International Commission on Radiological Protection). In superficial region, good agreement was achieved between MC simulation and film extrapolation method, with the mean differences less than 1%, 2% and 5% for 0°, 30° and 60°, respectively. The relative skin dose errors were 0.84%, 1.88% and 3.90%; the mean dose discrepancies (0°, 30° and 60°) between each of four algorithms and MC simulation were (2.41±1.55%, 3.11±2.40%, and 1.53±1.05%), (3.09±3.00%, 3.10±3.01%, and 3.77±3.59%), (3.16±1.50%, 8.70±2.84%, and 18.20±4.10%) and (14.45±4.66%, 10.74±4.54%, and 3.34±3.26%) for AXB, CCC, AAA and PBC respectively. Monte Carlo simulation verified the feasibility of the superficial dose measurements by multilayer Gafchromic films. And the rank

  14. Effects of low doses; Effet des faibles doses

    Energy Technology Data Exchange (ETDEWEB)

    Le Guen, B. [Electricite de France (EDF-LAM-SCAST), 93 - Saint-Denis (France)

    2001-07-01

    Actually, even though it is comfortable for the risk management, the hypothesis of the dose-effect relationship linearity is not confirmed for any model. In particular, in the area of low dose rate delivered by low let emitters. this hypothesis is debated at the light of recent observations, notably these ones relative to the mechanisms leading to genetic instability and induction eventuality of DNA repair. The problem of strong let emitters is still to solve. (N.C.)

  15. Hanford Environmental Dose Reconstruction Project

    Energy Technology Data Exchange (ETDEWEB)

    Finch, S.M.; McMakin, A.H. (comps.)

    1991-01-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is being managed and conducted by the Pacific Northwest Laboratory (PNL) under the direction of an independent Technical Steering Panel (TSP). The TSP consists of experts in environmental pathways, epidemiology, surface-water transport, ground-water transport, statistics, demography, agriculture, meteorology, nuclear engineering, radiation dosimetry, and cultural anthropology. Included are appointed technical members representing the states of Oregon and Washington, a representative of Native American tribes, and an individual representing the public. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on human (dose estimates): Source Terms; Environmental Transport; Environmental Monitoring Data; Demographics, Agriculture, Food Habits and; Environmental Pathways and Dose Estimates.

  16. Hanford Environmental Dose Reconstruction Project

    Energy Technology Data Exchange (ETDEWEB)

    McMakin, A.H.; Cannon, S.D.; Finch, S.M. (comps.)

    1992-07-01

    The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The TSP consists of experts in environmental pathways, epidemiology, surface-water transport, ground-water transport, statistics, demography, agriculture, meteorology, nuclear engineering, radiation dosimetry, and cultural anthropology. Included are appointed technical members representing the states of Oregon, Washington, and Idaho, a representative of Native American tribes, and an individual representing the public. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates): Source terms, environmental transport, environmental monitoring data, demography, food consumption, and agriculture, and environmental pathways and dose estimates. Progress is discussed.

  17. Minimal Erythema Dose (MED) testing.

    Science.gov (United States)

    Heckman, Carolyn J; Chandler, Rachel; Kloss, Jacqueline D; Benson, Amy; Rooney, Deborah; Munshi, Teja; Darlow, Susan D; Perlis, Clifford; Manne, Sharon L; Oslin, David W

    2013-05-28

    Ultraviolet radiation (UV) therapy is sometimes used as a treatment for various common skin conditions, including psoriasis, acne, and eczema. The dosage of UV light is prescribed according to an individual's skin sensitivity. Thus, to establish the proper dosage of UV light to administer to a patient, the patient is sometimes screened to determine a minimal erythema dose (MED), which is the amount of UV radiation that will produce minimal erythema (sunburn or redness caused by engorgement of capillaries) of an individual's skin within a few hours following exposure. This article describes how to conduct minimal erythema dose (MED) testing. There is currently no easy way to determine an appropriate UV dose for clinical or research purposes without conducting formal MED testing, requiring observation hours after testing, or informal trial and error testing with the risks of under- or over-dosing. However, some alternative methods are discussed.

  18. High dose irradiation with hyperfractionation

    Energy Technology Data Exchange (ETDEWEB)

    Asakura, Hideo; Kurashima, Shoji; Hasegawa, Maki; Akiyama, Kazuo (Sagamihara National Hospital, Kanagawa (Japan))

    1990-10-01

    From March 1988 to January 1990, 12 patients including 7 primary lung cancers, 2 lung metastases of colorectal cancer, and each 1 gall bladder cancer, ovarian cancer, and spinal cord metastasis of prostatic cancer, received {sup 60}Co-irradiation with high dose by hyperfractionation. This hyperfractionation consisted of 1.2 Gy per fraction, twice a day with 6 hour interval, and 5 days (10 fractions) a week. The total dose administered was 81.6{approx}100 Gy. The acute reaction of skin, lung, and intestines was tolerable, and it seemed that the late damage of normal tissues was slighter and the treatment result was favorable in comparison with the conventional fractionation, but this estimation was not definite because of short observation period. It was discussed that further reduction of dose per fraction (1 Gy or below) and more increased total dose (100 Gy or more) would be promising in hyperfractionation. (author).

  19. The dose makes the medicine.

    Science.gov (United States)

    Stumpf, Walter E

    2006-06-01

    Dose and time considerations in the development and use of a drug are important for assessing actions and side effects, as well as predictions of safety and toxicity. This article deals with epistemological aspects of dose selection by probing into the linguistic and cultural roots for the measure of medicine mediated by the medical doctor. Because toxicity is related to dose, historic and recent views suggest that less can be more. At low, medium and high dose levels, effects can differ not only quantitatively but also qualitatively. Dose-related target activation and recognition of enantiodromic thresholds between beneficial and toxic effects require elucidation of underlying events. Such studies, including hormesis and microdosing, call for extended ADME procedures with high-resolution methods in addition to the current low-resolution approaches. Improved information of drug logistics and target pharmacokinetics enables effective drug selection, dose determination and prediction. It also allows considerations of systems biology [i.e. integral (gestalt) pharmacology] exemplified by the drug homunculus, as in the case of vitamin D, that might lead to new paradigms and drug design.

  20. BENCHMARK DOSE TECHNICAL GUIDANCE DOCUMENT ...

    Science.gov (United States)

    The U.S. EPA conducts risk assessments for an array of health effects that may result from exposure to environmental agents, and that require an analysis of the relationship between exposure and health-related outcomes. The dose-response assessment is essentially a two-step process, the first being the definition of a point of departure (POD), and the second extrapolation from the POD to low environmentally-relevant exposure levels. The benchmark dose (BMD) approach provides a more quantitative alternative to the first step in the dose-response assessment than the current NOAEL/LOAEL process for noncancer health effects, and is similar to that for determining the POD proposed for cancer endpoints. As the Agency moves toward harmonization of approaches for human health risk assessment, the dichotomy between cancer and noncancer health effects is being replaced by consideration of mode of action and whether the effects of concern are likely to be linear or nonlinear at low doses. Thus, the purpose of this project is to provide guidance for the Agency and the outside community on the application of the BMD approach in determining the POD for all types of health effects data, whether a linear or nonlinear low dose extrapolation is used. A guidance document is being developed under the auspices of EPA's Risk Assessment Forum. The purpose of this project is to provide guidance for the Agency and the outside community on the application of the benchmark dose (BMD) appr

  1. Weldon Spring historical dose estimate

    Energy Technology Data Exchange (ETDEWEB)

    Meshkov, N.; Benioff, P.; Wang, J.; Yuan, Y.

    1986-07-01

    This study was conducted to determine the estimated radiation doses that individuals in five nearby population groups and the general population in the surrounding area may have received as a consequence of activities at a uranium processing plant in Weldon Spring, Missouri. The study is retrospective and encompasses plant operations (1957-1966), cleanup (1967-1969), and maintenance (1969-1982). The dose estimates for members of the nearby population groups are as follows. Of the three periods considered, the largest doses to the general population in the surrounding area would have occurred during the plant operations period (1957-1966). Dose estimates for the cleanup (1967-1969) and maintenance (1969-1982) periods are negligible in comparison. Based on the monitoring data, if there was a person residing continually in a dwelling 1.2 km (0.75 mi) north of the plant, this person is estimated to have received an average of about 96 mrem/yr (ranging from 50 to 160 mrem/yr) above background during plant operations, whereas the dose to a nearby resident during later years is estimated to have been about 0.4 mrem/yr during cleanup and about 0.2 mrem/yr during the maintenance period. These values may be compared with the background dose in Missouri of 120 mrem/yr.

  2. Isobio software: biological dose distribution and biological dose volume histogram from physical dose conversion using linear-quadratic-linear model

    National Research Council Canada - National Science Library

    Tanwiwat Jaikuna; Phatchareewan Khadsiri; Nisa Chawapun; Suwit Saekho; Ekkasit Tharavichitkul

    2017-01-01

      Purpose: To develop an in-house software program that is able to calculate and generate the biological dose distribution and biological dose volume histogram by physical dose conversion using the linear-quadratic-linear (LQL) model...

  3. Dose assessments for SFR 1

    Energy Technology Data Exchange (ETDEWEB)

    Bergstroem, Ulla (Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden)); Avila, Rodolfo; Ekstroem, Per-Anders; Cruz, Idalmis de la (Facilia AB, Bromma (Sweden))

    2008-06-15

    Following a review by the Swedish regulatory authorities of the safety analysis of the SFR 1 disposal facility for low and intermediate level waste, SKB has prepared an updated safety analysis, SAR-08. This report presents estimations of annual doses to the most exposed groups from potential radionuclide releases from the SFR 1 repository for a number of calculation cases, selected using a systematic approach for identifying relevant scenarios for the safety analysis. The dose estimates can be used for demonstrating that the long term safety of the repository is in compliance with the regulatory requirements. In particular, the mean values of the annual doses can be used to estimate the expected risks to the most exposed individuals, which can then be compared with the regulatory risk criteria for human health. The conversion from doses to risks is performed in the main report. For one scenario however, where the effects of an earthquake taking place close to the repository are analysed, risk calculations are presented in this report. In addition, prediction of concentrations of radionuclides in environmental media, such as water and soil, are compared with concentration limits suggested by the Erica-project as a base for estimating potential effects on the environment. The assessment of the impact on non-human biota showed that the potential impact is negligible. Committed collective dose for an integration period of 10,000 years for releases occurring during the first thousand years after closure are also calculated. The collective dose commitment was estimated to be 8 manSv. The dose calculations were carried out for a period of 100,000 years, which was sufficient to observe peak doses in all scenarios considered. Releases to the landscape and to a well were considered. The peaks of the mean annual doses from releases to the landscape are associated with C-14 releases to a future lake around year 5,000 AD. In the case of releases to a well, the peak annual doses

  4. Radiation dose monitoring in the clinical routine

    Energy Technology Data Exchange (ETDEWEB)

    Guberina, Nika [UK Essen (Germany). Radiology

    2017-04-15

    Here we describe the first clinical experiences regarding the use of an automated radiation dose management software to monitor the radiation dose of patients during routine examinations. Many software solutions for monitoring radiation dose have emerged in the last decade. The continuous progress in radiological techniques, new scan features, scanner generations and protocols are the primary challenge for radiation dose monitoring software systems. To simulate valid dose calculations, radiation dose monitoring systems have to follow current trends and stay constantly up-to-date. The dose management software is connected to all devices at our institute and conducts automatic data acquisition and radiation dose calculation. The system incorporates 18 virtual phantoms based on the Cristy phantom family, estimating doses in newborns to adults. Dose calculation relies on a Monte Carlo simulation engine. Our first practical experiences demonstrate that the software is capable of dose estimation in the clinical routine. Its implementation and use have some limitations that can be overcome. The software is promising and allows assessment of radiation doses, like organ and effective doses according to ICRP 60 and ICRP 103, patient radiation dose history and cumulative radiation doses. Furthermore, we are able to determine local diagnostic reference doses. The radiation dose monitoring software systems can facilitate networking between hospitals and radiological departments, thus refining radiation doses and implementing reference doses at substantially lower levels.

  5. Fluzone High-Dose Seasonal Influenza Vaccine

    Science.gov (United States)

    ... Variant Pandemic Other Fluzone High-Dose Seasonal Influenza Vaccine Questions & Answers Language: English (US) Español Recommend on ... flu season. What is Fluzone High-Dose influenza vaccine? Fluzone High-Dose is an influenza vaccine, manufactured ...

  6. Radiological dose assessment for vault storage concepts

    Energy Technology Data Exchange (ETDEWEB)

    Richard, R.F.

    1997-02-25

    This radiological dose assessment presents neutron and photon dose rates in support of project W-460. Dose rates are provided for a single 3013 container, the ``infloor`` storage vault concept, and the ``cubicle`` storage vault concept.

  7. AGING FACILITY WORKER DOSE ASSESSMENT

    Energy Technology Data Exchange (ETDEWEB)

    R.L. Thacker

    2005-03-24

    The purpose of this calculation is to estimate radiation doses received by personnel working in the Aging Facility performing operations to transfer aging casks to the aging pads for thermal and logistical management, stage empty aging casks, and retrieve aging casks from the aging pads for further processing in other site facilities. Doses received by workers due to aging cask surveillance and maintenance operations are also included. The specific scope of work contained in this calculation covers both collective doses and individual worker group doses on an annual basis, and includes the contributions due to external and internal radiation from normal operation. There are no Category 1 event sequences associated with the Aging Facility (BSC 2004 [DIRS 167268], Section 7.2.1). The results of this calculation will be used to support the design of the Aging Facility and to provide occupational dose estimates for the License Application. The calculations contained in this document were developed by Environmental and Nuclear Engineering of the Design and Engineering Organization and are intended solely for the use of the Design and Engineering Organization in its work regarding facility operation. Yucca Mountain Project personnel from the Environmental and Nuclear Engineering should be consulted before use of the calculations for purposes other than those stated herein or use by individuals other than authorized personnel in Environmental and Nuclear Engineering.

  8. Do dose area product meter measurements reflect radiation doses ...

    African Journals Online (AJOL)

    Enrique

    accurately measures the radiation emitted from the source. The study included the interventional radiolo ... mined as most sensitive to radiation. The use of a thyroid guard also decreases the effective dose by approx- ... al radiation is necessary. Thermo- luminescent dosimetry is used to measure radiation and the apparatus.

  9. Performance standard for dose Calibrator

    CERN Document Server

    Darmawati, S

    2002-01-01

    Dose calibrator is an instrument used in hospitals to determine the activity of radionuclide for nuclear medicine purposes. International Electrotechnical Commission (IEC) has published IEC 1303:1994 standard that can be used as guidance to test the performance of the instrument. This paper briefly describes content of the document,as well as explains the assessment that had been carried out to test the instrument accuracy in Indonesia through intercomparison measurement.Its is suggested that hospitals acquire a medical physicist to perform the test for its dose calibrator. The need for performance standard in the form of Indonesia Standard is also touched.

  10. Routine High Dose Excretory Urography

    Science.gov (United States)

    Gronner, Arthur T.; Arkoff, Robert S.; Burhenne, H. Joachim

    1967-01-01

    Radiologic evaluation of 316 excretory urograms utilizing a single 50 ml injection of a 50 to 60 per cent tri-iodinated contrast medium indicated that these studies are of better quality than those previously obtained with the injection of 30 ml. The low incidence of side effects coincides with recent reports in the literature that this dosage level is safe. High dose intravenous drip infusion pyelography was necessary only in selected cases. High dose excretory urography is recommended for routine use. ImagesFigure 1A, 1BFigure 2. PMID:6045483

  11. Confectionery-based dose forms.

    Science.gov (United States)

    Tangso, Kristian J; Ho, Quy Phuong; Boyd, Ben J

    2015-01-01

    Conventional dosage forms such as tablets, capsules and syrups are prescribed in the normal course of practice. However, concerns about patient preferences and market demands have given rise to the exploration of novel unconventional dosage forms. Among these, confectionery-based dose forms have strong potential to overcome compliance problems. This report will review the availability of these unconventional dose forms used in treating the oral cavity and for systemic drug delivery, with a focus on medicated chewing gums, medicated lollipops, and oral bioadhesive devices. The aim is to stimulate increased interest in the opportunities for innovative new products that are available to formulators in this field, particularly for atypical patient populations.

  12. LOW DOSE INTRAVAGINAL MISOPROSTOL VERSUS ...

    African Journals Online (AJOL)

    hi-tech

    2003-02-02

    Feb 2, 2003 ... for oxytocin augmentation was less in the misoprostol group (RR 0.76, 95% CI 0.64 to 0.91). No significant differences existed in rates for uterine hyperstimulation,. Caesarean section, maternal and neonatal morbidity. Conclusion: Intravaginal misoprostol in a low dose was compared to intracervical balloon.

  13. [Absorbed doses in dental radiology].

    Science.gov (United States)

    Bianchi, S D; Roccuzzo, M; Albrito, F; Ragona, R; Anglesio, S

    1996-01-01

    The growing use of dento-maxillo-facial radiographic examinations has been accompanied by the publication of a large number of studies on dosimetry. A thorough review of the literature is presented in this article. Most studies were carried out on tissue equivalent skull phantoms, while only a few were in vivo. The aim of the present study was to evaluate in vivo absorbed doses during Orthopantomography (OPT). Full Mouth Periapical Examination (FMPE) and Intraoral Tube Panoramic Radiography (ITPR). Measurements were made on 30 patients, reproducing clinical conditions, in 46 anatomical sites, with 24 intra- and 22 extra-oral thermoluminiscent dosimeters (TLDS). The highest doses were measured, in orthopantomography, at the right mandibular angle (1899 mu Gy) in FMPE on the right naso-labial fold (5640 mu Gy and in ITPR on the palatal surface of the left second upper molar (1936 mu Gy). Intraoral doses ranged from 21 mu Gy, in orthopantomography, to 4494 mu Gy in FMPE. Standard errors ranged from 142% in ITPR to 5% in orthopantomography. The highest rate of standard errors was found in FMPE and ITPR. The data collected in this trial are in agreement with others in major literature reports. Disagreements are probably due to different exam acquisition and data collections. Such differences, presented comparison in several sites, justify lower doses in FMPE and ITPR. Advantages and disadvantages of in vivo dosimetry of the maxillary region are discussed, the former being a close resemblance to clinical conditions of examination and the latter the impossibility of collecting values in depth of tissues. Finally, both ITPR and FMPE required lower doses than expected, and can be therefore reconsidered relative to their radiation risk.

  14. Sesame allergy threshold dose distribution.

    Science.gov (United States)

    Dano, D; Remington, B C; Astier, C; Baumert, J L; Kruizinga, A G; Bihain, B E; Taylor, S L; Kanny, G

    2015-09-01

    Sesame is a relevant food allergen in France. Compared to other allergens there is a lack of food challenge data and more data could help sesame allergy risk management. The aim of this study is to collect more sesame challenge data and investigate the most efficient food challenge method for future studies. Records of patients at University Hospital in Nancy (France) with objective symptoms to sesame challenges were collected and combined with previously published data. An estimation of the sesame allergy population threshold was calculated based on individual NOAELs and LOAELs. Clinical dosing schemes at Nancy were investigated to see if the optimal protocol for sesame is currently used. Fourteen patients (10 M/4 F, 22 ± 14.85 years old) with objective symptoms were added to previously published data making a total of 35 sesame allergic patients. The most sensitive patient reacted to the first dose at challenge of 1.02 mg sesame protein. The ED05 ranges between 1.2 and 4.0 mg of sesame protein (Log-Normal, Log-Logistic, and Weibull models) and the ED10 between 4.2 and 6.2 mg. The optimal food challenge dosing scheme for sesame follows semi-log dose increases from 0.3 to 3000 mg protein. This article provides a valuable update to the existing clinical literature regarding sesame NOAELs and LOAELs. Establishment of a population threshold for sesame could help in increasing the credibility of precautionary labelling and decrease the costs associated with unexpected allergic reactions. Also, the use of an optimal dosing scheme would decrease time spent on diagnostic and thereafter on the economic burden of sesame allergy diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Investigations of peripheral dose for helical tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lissner, Steffen; Schubert, Kai; Sterzing, Florian; Herfarth, Klaus; Sroka-Perez, Gabriele; Debus, Juergen [University Hospital Heidelberg (Germany). Dept. of Radiation Oncology; Wiezorek, Tilo [University Hospital Jena (Germany). Dept. of Radiotherapy

    2013-07-01

    Purpose: Whenever treating a patient with percutaneous radiotherapy, a certain amount of dose is inevitably delivered to healthy tissue. This is mainly due to beam's entry and exit in the region of the target volume. In regions distant from the target volume, dose is delivered by leakage from the MLC and head scatter from the accelerator head and phantom scatter from the target volume (peripheral dose). Helical tomotherapy is a form of radiation therapy with a uniquely designed machine and delivery pattern which influence the peripheral dose. The goal of this work was to investigate peripheral dose in helical tomotherapy. The experiments were used to establish a complex characterization of the peripheral dose. Materials and methods: A 30*30*60cm{sup 3} slab phantom and TLD-100 (Lithium fluoride) were used for the experiments. Treatment procedures were generated with the tomotherapy planning system (TPS). Additionally, procedures were created on the Operator Station of the tomotherapy system without a calculation of the dose distribution. The peripheral dose which was produced by a typical tomotherapy treatment plan was measured. Furthermore, these procedures were used to differentiate the parts of the peripheral dose in phantom scatter dose and head scatter and leakage dose. Additionally, the relation between peripheral dose and treatment time and between peripheral dose and delivered dose was investigated. Additionally, the peripheral dose was measured in an Alderson phantom. Results: Distances of 30cm or more resulted in a decrease of the peripheral dose to less than 0.1% of the target dose. The measured doses have an offset of approximately 1cGy in comparison to the calculated doses from the TPS. The separated head scatter and leakage dose was measured in the range of 1cGy for typical treatments. Furthermore, the investigations show a linear correlation between head scatter leakage dose and treatment time and between scatter dose parts and delivered dose. A

  16. Atmospheric radiation flight dose rates

    Science.gov (United States)

    Tobiska, W. K.

    2015-12-01

    Space weather's effects upon the near-Earth environment are due to dynamic changes in the energy transfer processes from the Sun's photons, particles, and fields. Of the domains that are affected by space weather, the coupling between the solar and galactic high-energy particles, the magnetosphere, and atmospheric regions can significantly affect humans and our technology as a result of radiation exposure. Space Environment Technologies (SET) has been conducting space weather observations of the atmospheric radiation environment at aviation altitudes that will eventually be transitioned into air traffic management operations. The Automated Radiation Measurements for Aerospace Safety (ARMAS) system and Upper-atmospheric Space and Earth Weather eXperiment (USEWX) both are providing dose rate measurements. Both activities are under the ARMAS goal of providing the "weather" of the radiation environment to improve aircraft crew and passenger safety. Over 5-dozen ARMAS and USEWX flights have successfully demonstrated the operation of a micro dosimeter on commercial aviation altitude aircraft that captures the real-time radiation environment resulting from Galactic Cosmic Rays and Solar Energetic Particles. The real-time radiation exposure is computed as an effective dose rate (body-averaged over the radiative-sensitive organs and tissues in units of microsieverts per hour); total ionizing dose is captured on the aircraft, downlinked in real-time, processed on the ground into effective dose rates, compared with NASA's Langley Research Center (LaRC) most recent Nowcast of Atmospheric Ionizing Radiation System (NAIRAS) global radiation climatology model runs, and then made available to end users via the web and smart phone apps. Flight altitudes now exceed 60,000 ft. and extend above commercial aviation altitudes into the stratosphere. In this presentation we describe recent ARMAS and USEWX results.

  17. [Single dose treatment of trichomoniasis].

    Science.gov (United States)

    Erb, H

    1975-01-01

    The present regiman for the treatment of trichomoniasis with Tinidazol is 150 mg. twice daily for 7 days with a total dose of 2,100 mg. The success rate of this regimen is 85-90%. With a single dosage treatment of 2,000 mg. (Four 500 mg. tablets for the patient and her sexual partner) the success rate improved to 100%. Toxic side effects were not observed. The treatment was well tolerated and well accepted.

  18. Tolerance doses for treatment planning

    Energy Technology Data Exchange (ETDEWEB)

    Lyman, J.T.

    1985-10-01

    Data for the tolerance of normal tissues or organs to (low-LET) radiation has been compiled from a number of sources which are referenced at the end of this document. This tolerance dose data are ostensibly for uniform irradiation of all or part of an organ, and are for either 5% (TD/sub 5/) or 50% (TD/sub 50/) complication probability. The ''size'' of the irradiated organ is variously stated in terms of the absolute volume or the fraction of the organ volume irradiated, or the area or the length of the treatment field. The accuracy of these data is questionable. Much of the data represents doses that one or several experienced therapists have estimated could be safely given rather than quantitative analyses of clinical observations. Because these data have been obtained from multiple sources with possible different criteria for the definition of a complication, there are sometimes different values for what is apparently the same endpoint. The data from some sources shows a tendancy to be quantized in 5 Gy increments. This reflects the size of possible round off errors. It is believed that all these data have been accumulated without the benefit of 3-D dose distributions and therefore the estimates of the size of the volume and/or the uniformity of the irradiation may be less accurate than is now possible. 19 refs., 4 figs.

  19. Converting absorbed dose to medium to absorbed dose to water for Monte Carlo based photon beam dose calculations

    Science.gov (United States)

    Siebers, J. V.; Keall, P. J.; Nahum, A. E.; Mohan, R.

    2000-04-01

    Current clinical experience in radiation therapy is based upon dose computations that report the absorbed dose to water, even though the patient is not made of water but of many different types of tissue. While Monte Carlo dose calculation algorithms have the potential for higher dose accuracy, they usually transport particles in and compute the absorbed dose to the patient media such as soft tissue, lung or bone. Therefore, for dose calculation algorithm comparisons, or to report dose to water or tissue contained within a bone matrix for example, a method to convert dose to the medium to dose to water is required. This conversion has been developed here by applying Bragg-Gray cavity theory. The dose ratio for 6 and 18 MV photon beams was determined by computing the average stopping power ratio for the primary electron spectrum in the transport media. For soft tissue, the difference between dose to medium and dose to water is approximately 1.0%, while for cortical bone the dose difference exceeds 10%. The variation in the dose ratio as a function of depth and position in the field indicates that for photon beams a single correction factor can be used for each particular material throughout the field for a given photon beam energy. The only exception to this would be for the clinically non-relevant dose to air. Pre-computed energy spectra for 60 Co to 24 MV are used to compute the dose ratios for these photon beams and to determine an effective energy for evaluation of the dose ratio.

  20. Loratadine: multiple-dose pharmacokinetics.

    Science.gov (United States)

    Radwanski, E; Hilbert, J; Symchowicz, S; Zampaglione, N

    1987-07-01

    The steady-state pharmacokinetics of loratadine (L), a new long-acting antihistamine devoid of CNS activity, was investigated in 12 healthy male volunteers. Each volunteer received 40-mg L capsules q24h for ten days. Blood samples were collected at various times on day 1, 5, 7, and 10 and assayed for L by radioimmunoassay (RIA) and for descarboethoxyloratadine (DCL), a known active metabolite, by high-performance liquid chromatography (HPLC). The plasma L and DCL concentration-time data in the disposition phases were fitted to a biexponential equation for pharmacokinetic analysis. Steady-state plasma L Cmax concentrations were reached at 1.5 hour (Tmax) after each dose. DCL steady-state Cmax values ranged 26 to 29 ng/mL at a Tmax ranging from 1.8 to 3 hours. The AUC at steady state, AUC tau, was 80 to 96 and 349 to 421 h X ng/mL for L and DCL, respectively. The accumulation indexes (Ra) based on AUC tau ratios, did not change for either compound after day 5. Ra values for L and DCL after the fifth dose were 1.4 and 1.9, respectively, indicating that there is little accumulation of either L or DCL after a multiple (once-a-day) dosage regimen. The t1/2 beta at steady state were 14.4 and 18.7 hours for L and DCL, respectively, which were similar to those reported following a single-dose L administration. Observed plasma drug concentrations were in good agreement with predicted values derived for pharmacokinetic parameters.

  1. Low-dose radiation exposure and carcinogenesis

    National Research Council Canada - National Science Library

    Suzuki, Keiji; Yamashita, Shunichi

    2012-01-01

    .... Epidemiological studies have demonstrated the dose-response relationships for cancer induction and quantitative evaluations of cancer risk following exposure to moderate to high doses of low-linear...

  2. Dose-mapping distribution around MNSR

    CERN Document Server

    Jamal, M H

    2002-01-01

    The aim of this study is to establish the dose-rate map through the determination of radiological dose-rate levels in reactor hall, adjacent rooms, and outside the MNSR facility. Controlling dose rate to reactor operating personnel , dose map was established. The map covers time and distances in the reactor hall, during reactor operation at nominal power. Different measurement of dose rates in other areas of the reactor buildings was established. The maximum dose rate, during normal operation of the MNSR was 40 and 21 Sv/hr on the top of the reactor and near the pool fence, respectively. Whereas, gamma and neutron doses have not exceeded natural background in all rooms adjacent to the reactor hall or nearly buildings. The relation between the dose rate for gamma rays and neutron flux at the top of cover of reactor pool was studied as well. It was found that this relation is linear.

  3. Dose to water versus dose to medium in proton beam therapy

    Science.gov (United States)

    Paganetti, Harald

    2009-07-01

    Dose in radiation therapy is traditionally reported as the water-equivalent dose, or dose to water. Monte Carlo dose calculations report dose to medium and thus a methodology is needed to convert dose to medium into dose to water (or vice versa) for comparison of Monte Carlo results with results from planning systems. This paper describes the development of a formalism to convert dose to medium into dose to water for proton fields when simulating the dose with Monte Carlo techniques. The conversion is based on relative stopping power but also considers energy transferred via nuclear interactions. The influence of different interaction mechanisms of proton beams (electromagnetic versus nuclear) is demonstrated. Further, an approximate method for converting doses retroactively is presented. Based on the outlined formalism, five proton therapy patients with a total of 33 fields were analyzed. Dose distributions, dose volume histograms and absolute doses to assess the clinical significance of differences between dose to medium and dose to water are presented. We found that the difference between the two dose reporting definitions can be up to 10% for high CT numbers if analyzing the mean dose to the target. The difference is clinically insignificant for soft tissues. For the structures analyzed, the mean dose to water could be converted to dose to medium by applying a correction factor increasing linearly with increasing average CT number in the volume. We determined that an approximate conversion method, done retroactively with an energy-independent stopping power ratio and without considering nuclear interaction events separately (as compared to on-the-fly conversion during simulation), is sufficiently accurate to compute mean doses. It is insufficient, however, when analyzing the beam range. For proton beams stopping in bony anatomy, the predicted beam range can differ by 2-3 mm when comparing dose to tissue and dose to water.

  4. Genetic warfarin dosing: tables versus algorithms.

    Science.gov (United States)

    Finkelman, Brian S; Gage, Brian F; Johnson, Julie A; Brensinger, Colleen M; Kimmel, Stephen E

    2011-02-01

    The aim of this study was to compare the accuracy of genetic tables and formal pharmacogenetic algorithms for warfarin dosing. Pharmacogenetic algorithms based on regression equations can predict warfarin dose, but they require detailed mathematical calculations. A simpler alternative, recently added to the warfarin label by the U.S. Food and Drug Administration, is to use genotype-stratified tables to estimate warfarin dose. This table may potentially increase the use of pharmacogenetic warfarin dosing in clinical practice; however, its accuracy has not been quantified. A retrospective cohort study of 1,378 patients from 3 anticoagulation centers was conducted. Inclusion criteria were stable therapeutic warfarin dose and complete genetic and clinical data. Five dose prediction methods were compared: 2 methods using only clinical information (empiric 5 mg/day dosing and a formal clinical algorithm), 2 genetic tables (the new warfarin label table and a table based on mean dose stratified by genotype), and 1 formal pharmacogenetic algorithm, using both clinical and genetic information. For each method, the proportion of patients whose predicted doses were within 20% of their actual therapeutic doses was determined. Dosing methods were compared using McNemar's chi-square test. Warfarin dose prediction was significantly more accurate (all p algorithm (52%) than with all other methods: empiric dosing (37%; odds ratio [OR]: 2.2), clinical algorithm (39%; OR: 2.2), warfarin label (43%; OR: 1.8), and genotype mean dose table (44%; OR: 1.9). Although genetic tables predicted warfarin dose better than empiric dosing, formal pharmacogenetic algorithms were the most accurate. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. Hanford Environmental Dose Reconstruction Project. Monthly report

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, S.D.; Finch, S.M. [comps.

    1992-10-01

    The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The independent Technical Steering Panel (TSP) provides technical direction. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates):Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates.

  6. CT radiation dose and iterative reconstruction techniques.

    Science.gov (United States)

    Padole, Atul; Ali Khawaja, Ranish Deedar; Kalra, Mannudeep K; Singh, Sarabjeet

    2015-04-01

    1. CT radiation dose optimization is one of the major concerns for the scientific community. 2. CT image quality is dependent on the selected image reconstruction algorithm. 3. Iterative reconstruction algorithms have reemerged with the potential of radiation dose optimization by lowering image noise. 4. Tube current is the most common parameter used to reduce radiation dose along with iterative reconstruction. 5. Tube potential (kV) is also used for dose optimization with iterative reconstruction in CT angiography protocols and small patients.

  7. Adaption By Low Dose Radiation Exposure

    OpenAIRE

    Mitchel, Ron E.J.

    2015-01-01

    The procedures and dose limitations used for radiation protection in the nuclear industry are founded on the assumption that risk is directly proportional to dose, without a threshold. Based on this idea that any dose, no matter how small, will increase risk, radiation protection regulations generally attempt to reduce any exposure to ?as low as reasonably achievable? (ALARA). We know however, that these regulatory assumptions are inconsistent with the known biological effects of low doses. L...

  8. Low-Dose Pretreatment for Radiation Therapy

    OpenAIRE

    Blankenbecler, Richard

    2010-01-01

    In radiotherapy, a large radiation dose must be applied to both cancer and neighboring healthy cells. Recent experiments have shown that a low dose of ionizing radiation turns on certain protective mechanisms that allow a cell to better survive a subsequent high dose of radiation. This adaptive response can have important and positive consequences for radiotherapy. This paper describes a simple change in treatment procedures to make use of these beneficial effects. A low dose applied only to ...

  9. A dose monitoring system for dental radiography

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chena; Lee, Sam Sun; Kim, Jo Eun; Huh, Kyung Hoe; Yi, Woo Jin; Heo, Min Suk; Choi, Soon Chul [Dept. of Oral and Maxillofacial Radiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Symkhampha, Khanthaly [Dept. of Oral and Maxillofacial Radiology, Department of Basic Science, Faculty of Dentistry, University of Health Sciences, Vientiane (Lao People' s Democratic Republic); Lee, Woo Jin [Dept. of Interdisciplinary Program in Radiation, Applied Life Sciences Major, College of Medicine, BK21, and Dental Research Institute, Seoul National University, Seoul (Korea, Republic of); Yeom, Heon Young [School of Computer Science Engineering, Seoul National University, Seoul (Korea, Republic of)

    2016-06-15

    The current study investigates the feasibility of a platform for a nationwide dose monitoring system for dental radiography. The essential elements for an unerring system are also assessed. An intraoral radiographic machine with 14 X-ray generators and five sensors, 45 panoramic radiographic machines, and 23 cone-beam computed tomography (CBCT) models used in Korean dental clinics were surveyed to investigate the type of dose report. A main server for storing the dose data from each radiographic machine was prepared. The dose report transfer pathways from the radiographic machine to the main sever were constructed. An effective dose calculation method was created based on the machine specifications and the exposure parameters of three intraoral radiographic machines, five panoramic radiographic machines, and four CBCTs. A viewing system was developed for both dentists and patients to view the calculated effective dose. Each procedure and the main server were integrated into one system. The dose data from each type of radiographic machine was successfully transferred to the main server and converted into an effective dose. The effective dose stored in the main server is automatically connected to a viewing program for dentist and patient access. A patient radiation dose monitoring system is feasible for dental clinics. Future research in cooperation with clinicians, industry, and radiologists is needed to ensure format convertibility for an efficient dose monitoring system to monitor unexpected radiation dose.

  10. Failure-probability driven dose painting

    DEFF Research Database (Denmark)

    Vogelius, Ivan R; Håkansson, Katrin; Due, Anne K

    2013-01-01

    To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study...

  11. Chemical Dosing and First-Order Kinetics

    Science.gov (United States)

    Hladky, Paul W.

    2011-01-01

    College students encounter a variety of first-order phenomena in their mathematics and science courses. Introductory chemistry textbooks that discuss first-order processes, usually in conjunction with chemical kinetics or radioactive decay, stop at single, discrete dose events. Although single-dose situations are important, multiple-dose events,…

  12. Doxycycline Compliance at Bagram Air Field

    Science.gov (United States)

    2014-05-01

    Completing Sex Survey Male 292 Female 132 Total 424 Table 3 - Rank Category of Members Taking Survey Number Completing Rank Category Survey E...oral contraceptives Jess effective? Number Completing Aware Survey Yes 97 No 327 Total 424 Table 32-Do You Use Prescribed Oral Contraceptives ...Use Prescribed Oral Number Completing Contraceptives Survey Yes 39 No 93 Total 132 21 Discussion The overall objective ofthis process

  13. Metrics, Dose, and Dose Concept: The Need for a Proper Dose Concept in the Risk Assessment of Nanoparticles

    Directory of Open Access Journals (Sweden)

    Myrtill Simkó

    2014-04-01

    Full Text Available In order to calculate the dose for nanoparticles (NP, (i relevant information about the dose metrics and (ii a proper dose concept are crucial. Since the appropriate metrics for NP toxicity are yet to be elaborated, a general dose calculation model for nanomaterials is not available. Here we propose how to develop a dose assessment model for NP in analogy to the radiation protection dose calculation, introducing the so-called “deposited and the equivalent dose”. As a dose metric we propose the total deposited NP surface area (SA, which has been shown frequently to determine toxicological responses e.g. of lung tissue. The deposited NP dose is proportional to the total surface area of deposited NP per tissue mass, and takes into account primary and agglomerated NP. By using several weighting factors the equivalent dose additionally takes into account various physico-chemical properties of the NP which are influencing the biological responses. These weighting factors consider the specific surface area, the surface textures, the zeta-potential as a measure for surface charge, the particle morphology such as the shape and the length-to-diameter ratio (aspect ratio, the band gap energy levels of metal and metal oxide NP, and the particle dissolution rate. Furthermore, we discuss how these weighting factors influence the equivalent dose of the deposited NP.

  14. Dose Titration Algorithm Tuning (DTAT) should supersede 'the' Maximum Tolerated Dose (MTD) in oncology dose-finding trials.

    Science.gov (United States)

    Norris, David C

    2017-01-01

    Background. Absent adaptive, individualized dose-finding in early-phase oncology trials, subsequent 'confirmatory' Phase III trials risk suboptimal dosing, with resulting loss of statistical power and reduced probability of technical success for the investigational therapy. While progress has been made toward explicitly adaptive dose-finding and quantitative modeling of dose-response relationships, most such work continues to be organized around a concept of 'the' maximum tolerated dose (MTD). The purpose of this paper is to demonstrate concretely how the aim of early-phase trials might be conceived, not as 'dose-finding', but as dose titration algorithm (DTA)-finding. Methods. A Phase I dosing study is simulated, for a notional cytotoxic chemotherapy drug, with neutropenia constituting the critical dose-limiting toxicity. The drug's population pharmacokinetics and myelosuppression dynamics are simulated using published parameter estimates for docetaxel. The amenability of this model to linearization is explored empirically. The properties of a simple DTA targeting neutrophil nadir of 500 cells/mm 3 using a Newton-Raphson heuristic are explored through simulation in 25 simulated study subjects. Results. Individual-level myelosuppression dynamics in the simulation model approximately linearize under simple transformations of neutrophil concentration and drug dose. The simulated dose titration exhibits largely satisfactory convergence, with great variance in individualized optimal dosing. Some titration courses exhibit overshooting. Conclusions. The large inter-individual variability in simulated optimal dosing underscores the need to replace 'the' MTD with an individualized concept of MTD i . To illustrate this principle, the simplest possible DTA capable of realizing such a concept is demonstrated. Qualitative phenomena observed in this demonstration support discussion of the notion of tuning such algorithms. Although here illustrated specifically in relation to

  15. Dose Titration Algorithm Tuning (DTAT) should supersede ‘the’ Maximum Tolerated Dose (MTD) in oncology dose-finding trials

    Science.gov (United States)

    Norris, David C.

    2017-01-01

    Background. Absent adaptive, individualized dose-finding in early-phase oncology trials, subsequent ‘confirmatory’ Phase III trials risk suboptimal dosing, with resulting loss of statistical power and reduced probability of technical success for the investigational therapy. While progress has been made toward explicitly adaptive dose-finding and quantitative modeling of dose-response relationships, most such work continues to be organized around a concept of ‘the’ maximum tolerated dose (MTD). The purpose of this paper is to demonstrate concretely how the aim of early-phase trials might be conceived, not as ‘dose-finding’, but as dose titration algorithm (DTA)-finding. Methods. A Phase I dosing study is simulated, for a notional cytotoxic chemotherapy drug, with neutropenia constituting the critical dose-limiting toxicity. The drug’s population pharmacokinetics and myelosuppression dynamics are simulated using published parameter estimates for docetaxel. The amenability of this model to linearization is explored empirically. The properties of a simple DTA targeting neutrophil nadir of 500 cells/mm 3 using a Newton-Raphson heuristic are explored through simulation in 25 simulated study subjects. Results. Individual-level myelosuppression dynamics in the simulation model approximately linearize under simple transformations of neutrophil concentration and drug dose. The simulated dose titration exhibits largely satisfactory convergence, with great variance in individualized optimal dosing. Some titration courses exhibit overshooting. Conclusions. The large inter-individual variability in simulated optimal dosing underscores the need to replace ‘the’ MTD with an individualized concept of MTD i . To illustrate this principle, the simplest possible DTA capable of realizing such a concept is demonstrated. Qualitative phenomena observed in this demonstration support discussion of the notion of tuning such algorithms. Although here illustrated specifically

  16. Optimizing lithium dosing in hemodialysis

    DEFF Research Database (Denmark)

    Bjarnason, N H; Munkner, R; Kampmann, J P

    2006-01-01

    We studied a 62-year-old female hemodialysis patient during initiation and maintenance of lithium carbonate therapy. Three different methods were applied to estimate the regimen: a scenario based on volume of distribution (V(d)), a scenario based on glomerular filtration rate (GFR), and a scenario...... estimates. Furthermore, the maintenance dose estimated from the central compartment (V1) led to plasma concentrations within the therapeutic range. Thus, a regimen where 12.2 mmol lithium was given after each hemodialysis session resulted in stable between-dialysis plasma lithium concentrations...... in this patient with no residual kidney function. We did not observe adverse effects related to this regimen, which was monitored from 18 days to 8 months of therapy, and the patient experienced relief from her severe depressive disorder. In conclusion, dialysis patients may be treated with lithium administrated...

  17. The Dose Makes The Cooperation

    CERN Document Server

    Cetin, Uzay

    2016-01-01

    Explaining cooperation is one of the greatest challenges for basic scientific research. We proposed an agent-based model to study co-evolution of memory and cooperation. In our model, reciprocal agents with limited memory size play Prisoner's Dilemma Game iteratively. The characteristic of the environment, whether it is threatening or not, is embedded in the payoff matrix. Our findings are as follows. (i) Memory plays a critical role in the protection of cooperation. (ii) In the absence of threat, subsequent generations loose their memory and are consequently invaded by defectors. (iii) In contrast, the presence of an appropriate level of threat triggers the emergence of a self-protection mechanism for cooperation within subsequent generations. On the evolutionary level, memory size acts like an immune response of the population against aggressive defection. (iv) Even more extreme threat results again in defection. Our findings boil down to the following: The dose of the threat makes the cooperation.

  18. Ambient dose equivalents in TGFs

    Science.gov (United States)

    Celestin, Sebastien; Pincon, Jean-Louis; Trompier, Francois

    2017-04-01

    Terrestrial gamma-ray flashes (TGFs) are bursts of high-energy photons originating from the Earth's atmosphere in association with thunderstorm activity [e.g., Briggs et al., JGR, 118, 3805, 2013]. TGFs are associated with initial propagation stages of intracloud lightning, which represent the most frequent type of lightning discharges [e.g., Cummer et al., GRL, 42, 7792, 2015, and references therein]. TGFs are known to be produced inside common thunderclouds [e.g., Splitt et al., JGR, 115, A00E38, 2010] typically at altitudes ranging from 10 to 14 km [e.g., Cummer et al., GRL, 41, 8586, 2014]. The global TGF occurrence rate is estimated to be 400,000 per year concerning TGFs detectable by Fermi-GBM (Gamma ray Burst Monitor) [Briggs et al., 2013], but detailed analysis of satellite measurements [Østgaard et al., JGR, 117, A03327, 2012] and theoretical studies [Celestin et al., JGR, 120, 10712, 2015] suggest that it cannot be excluded that TGFs represent a part of a regular process taking place during the propagation of lightning discharges. It is important to assess the risk induced by TGFs for airline passengers and crews on board aircraft approaching thunderstorms. Dwyer et al. [JGR, 115, D09206, 2010] have estimated that if an aircraft were to find itself in the source electron beam giving rise to a TGF, passengers and crews might receive effective radiation doses above the regulatory limit depending on the beam diameter. Moreover, Tavani et al. [Nat. Hazards Earth Syst. Sci., 13, 1127, 2013] concluded that TGF-associated neutrons produced by photonuclear reactions would cause serious hazard on the aircraft avionics. In this work, we will present detailed simulation-based estimations of effective doses received by humans that would be irradiated by TGFs for various production altitudes and distances from the TGF source.

  19. Exposure- and Dose-response Analyses in Dose Selection and Labeling of FDA-approved Biologics.

    Science.gov (United States)

    Ogasawara, Ken; Breder, Christopher D; Lin, Dora H; Alexander, G Caleb

    2018-01-01

    Biological drug products, or products derived from living cells, represent an increasingly important part of the pharmaceutical market. Despite this, little is known about how sponsors determine the dose to be studied in registrational trials or to be proposed in labeling for biologics. We examined how exposure-response and dose-response analyses were used to determine dosing in pivotal trials or the labeling for all biologics approved by the Center for Drug Evaluation and Research, the US Food and Drug Administration (FDA) between 2003 and 2016. We extracted relevant characteristics of each biologic from its review package by FDA. We used descriptive statistics to characterize the rationale for the selected dose(s) in registration trials, with a particular focus on the role of exposure-response/dose-response analyses. We also examined how exposure-response/dose-response analyses were used to support the labeling dose and the basis for postmarketing requirements or commitments related to dose optimization. A total of 79 biologics license applications were examined. Dose selection in registrational trials was more often attributed to clinical efficacy (73% of applications) than to clinical safety (42%). The dosing of products whose dose was apparently selected based on clinical efficacy was often (72%) determined by the dose-response relationship. In support of doses that were described in labeling, exposure-response analyses for efficacy were performed more commonly (53%) than dose-response analyses (21%). This trend was apparent after 2012. This is the first study to summarize the justification of dose selection and the labeled dose of biologics approved by the FDA. Dose-response analyses have been often used as the rationale for dose selection of registrational studies, although exposure-response analyses are becoming more prevalent in support of the dosing guidelines in labeling. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

  20. Prediction of midline dose from entrance ad exit dose using OSLD measurements for total irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Chang Heon; Park, Jong Min; Park, So Yeon; Chun, Min Soo; Han, Ji Hye; Cho, Jin Dong; Kim, Jung In [Dept. of Radiation Oncology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2017-06-15

    This study aims to predict the midline dose based on the entrance and exit doses from optically stimulated luminescence detector (OSLD) measurements for total body irradiation (TBI). For TBI treatment, beam data sets were measured for 6 MV and 15 MV beams. To evaluate the tissue lateral effect of various thicknesses, the midline dose and peak dose were measured using a solid water phantom (SWP) and ion chamber. The entrance and exit doses were measured using OSLDs. OSLDs were attached onto the central beam axis at the entrance and exit surfaces of the phantom. The predicted midline dose was evaluated as the sum of the entrance and exit doses by OSLD measurement. The ratio of the entrance dose to the exit dose was evaluated at various thicknesses. The ratio of the peak dose to the midline dose was 1.12 for a 30 cm thick SWP at both energies. When the patient thickness is greater than 30 cm, the 15 MV should be used to ensure dose homogeneity. The ratio of the entrance dose to the exit dose was less than 1.0 for thicknesses of less than 30 cm and 40 cm at 6 MV and 15 MV, respectively. Therefore, the predicted midline dose can be underestimated for thinner body. At 15 MV, the ratios were approximately 1.06 for a thickness of 50 cm. In cases where adult patients are treated with the 15 MV photon beam, it is possible for the predicted midline dose to be overestimated for parts of the body with a thickness of 50 cm or greater. The predicted midline dose and OSLD-measured midline dose depend on the phantom thickness. For in-vivo dosimetry of TBI, the measurement dose should be corrected in order to accurately predict the midline dose.

  1. Avaliação biofarmacotécnica in vitro de formas farmacêuticas sólidas contendo doxiciclina In vitro biopharmaceutical evaluation of solid dosage forms containing doxycycline

    Directory of Open Access Journals (Sweden)

    Geysa Aguiar

    2005-12-01

    commercial products available in the Brazilian market, containing 100 mg of doxycycline. The dissolution method described in the United States Pharmacopeia (USP was used for the dissolution kinetics analysis. It was evaluated by the parameters k s (dissolution rate constant, t50% (time to promote the dissolution of 50% of the drug in the pharmaceutical dosage form and dissolution efficacy. According to the results it was verified that all the batches were in accordance with official specifications for average weight, doxyxycline content, uniformity content, and dissolution tests. All produtcts showed first order dissolution kinetics. Dissolution efficacy values ranged from 58,48% to 78,39%.

  2. Dose optimisation in single plane interstitial brachytherapy.

    Science.gov (United States)

    Tanderup, Kari; Hellebust, Taran Paulsen; Honoré, Henriette Benedicte; Nielsen, Søren Kynde; Olsen, Dag Rune; Grau, Cai; Lindegaard, Jacob Christian

    2006-10-01

    Brachytherapy dose distributions can be optimised by modulation of source dwell times. In this study dose optimisation in single planar interstitial implants was evaluated in order to quantify the potential benefit in patients. In 14 patients, treated for recurrent rectal and cervical cancer, flexible catheters were sutured intra-operatively to the tumour bed in areas with compromised surgical margin. Both non-optimised, geometrically and graphically optimised CT -based dose plans were made. The overdose index (OI), homogeneity index (HI), conformal index (COIN), minimum target dose, and high dose volumes were evaluated. The dependence of OI, HI, and COIN on target volume and implant regularity was evaluated. In addition, 12 theoretical implant configurations were analyzed. Geometrical and graphical optimisation improved the dose plans significantly with graphical optimisation being superior. Graphically optimised dose plans showed a significant decrease of 18%+/-9% in high dose volume (p<0.001). HI, COIN, and OI were significantly improved from 0.50+/-0.05 to 0.60+/-0.05, from 0.65+/-0.04 to 0.71+/-0.04, and from 0.19+/-0.03 to 0.15+/-0.03, respectively (p<0.001 for all). Moreover, minimum target dose increased significantly from 71%+/-5% to 80%+/-5% (p<0.001). The improvement in OI and HI obtained by optimisation depended on the regularity of the implant, such that the benefit of optimisation was larger for irregular implants. OI and HI correlated strongly with target volume limiting the usability of these parameters for comparison of dose plans between patients. Dwell time optimisation significantly improved the dose distribution regarding homogeneity, conformity, minimum target dose, and size of high dose volumes. Graphical optimisation is fast, reproducible and superior to geometric optimisation.

  3. Failure-probability driven dose painting

    Energy Technology Data Exchange (ETDEWEB)

    Vogelius, Ivan R.; Håkansson, Katrin; Due, Anne K.; Aznar, Marianne C.; Kristensen, Claus A.; Rasmussen, Jacob; Specht, Lena [Department of Radiation Oncology, Rigshospitalet, University of Copenhagen, Copenhagen 2100 (Denmark); Berthelsen, Anne K. [Department of Radiation Oncology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark and Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen 2100 (Denmark); Bentzen, Søren M. [Department of Radiation Oncology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark and Departments of Human Oncology and Medical Physics, University of Wisconsin, Madison, Wisconsin 53792 (United States)

    2013-08-15

    Purpose: To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study using the optimized dose prescription in 20 patients is performed.Methods: Patients treated at our center have five tumor subvolumes from the center of the tumor (PET positive volume) and out delineated. The spatial distribution of 48 failures in patients with complete clinical response after (chemo)radiation is used to derive a model for tumor control probability (TCP). The total TCP is fixed to the clinically observed 70% actuarial TCP at five years. Additionally, the authors match the distribution of failures between the five subvolumes to the observed distribution. The steepness of the dose–response is extracted from the literature and the authors assume 30% and 20% risk of subclinical involvement in the elective volumes. The result is a five-compartment dose response model matching the observed distribution of failures. The model is used to optimize the distribution of dose in individual patients, while keeping the treatment intensity constant and the maximum prescribed dose below 85 Gy.Results: The vast majority of failures occur centrally despite the small volumes of the central regions. Thus, optimizing the dose prescription yields higher doses to the central target volumes and lower doses to the elective volumes. The dose planning study shows that the modified prescription is clinically feasible. The optimized TCP is 89% (range: 82%–91%) as compared to the observed TCP of 70%.Conclusions: The observed distribution of locoregional failures was used to derive an objective, data-driven dose prescription function. The optimized dose is predicted to result in a substantial increase in local control without increasing the predicted risk of toxicity.

  4. Switching From Age-Based Stimulus Dosing to Dose Titration Protocols in Electroconvulsive Therapy: Empirical Evidence for Better Patient Outcomes With Lower Peak and Cumulative Energy Doses.

    Science.gov (United States)

    O'Neill-Kerr, Alex; Yassin, Anhar; Rogers, Stephen; Cornish, Janie

    2017-09-01

    The aim of this study was to test the proposition that adoption of a dose titration protocol may be associated with better patient outcomes, at lower treatment dose, and with comparable cumulative dose to that in patients treated using an age-based stimulus dosing protocol. This was an analysis of data assembled from archived records and based on cohorts of patients treated respectively on an age-based stimulus dosing protocol and on a dose titration protocol in the National Health Service in England. We demonstrated a significantly better response in the patient cohort treated with dose titration than with age-based stimulus dosing. Peak doses were less and the total cumulative dose was less in the dose titration group than in the age-based stimulus dosing group. Our findings are consistent with superior outcomes in patients treated using a dose titration protocol when compared with age-based stimulus dosing in a similar cohort of patients.

  5. Hanford Environmental Dose Reconstruction Project monthly report

    Energy Technology Data Exchange (ETDEWEB)

    Finch, S.M. [comp.

    1991-10-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doeses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): Source terms; environmental transport; environmental monitoring data; demographics, agriculture, food habits; environmental pathways and dose estimates.

  6. Converting low dose radiation to redox signaling

    OpenAIRE

    Pristov, Jelena Bogdanović; Spasić, Mihajlo; Spasojević, Ivan

    2013-01-01

    In contrast to the damaging effects of high doses, low dose radiation (UV, gamma) has been reported to provoke constructive changes in plants. However, the mechanisms by which plants recognize and respond to low dose radiation are not understood. We have shown recently that polygalacturonic acid, cell wall polysaccharide, converts the highly reactive product of radiation - hydroxyl radical into superoxide which may be further dismutated to hydrogen peroxide. Superoxide has been proposed to ac...

  7. Neutrons in active proton therapy. Parameterization of dose and dose equivalent

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Uwe; Haelg, Roger A. [Univ. of Zurich (Switzerland). Dept. of Physics; Radiotherapy Hirslanden AG, Aarau (Switzerland); Lomax, Tony [Paul Scherrer Institute, Villigen (Switzerland). Center for Proton Therapy

    2017-08-01

    One of the essential elements of an epidemiological study to decide if proton therapy may be associated with increased or decreased subsequent malignancies compared to photon therapy is an ability to estimate all doses to non-target tissues, including neutron dose. This work therefore aims to predict for patients using proton pencil beam scanning the spatially localized neutron doses and dose equivalents. The proton pencil beam of Gantry 1 at the Paul Scherrer Institute (PSI) was Monte Carlo simulated using GEANT. Based on the simulated neutron dose and neutron spectra an analytical mechanistic dose model was developed. The pencil beam algorithm used for treatment planning at PSI has been extended using the developed model in order to calculate the neutron component of the delivered dose distribution for each treated patient. The neutron dose was estimated for two patient example cases. The analytical neutron dose model represents the three-dimensional Monte Carlo simulated dose distribution up to 85 cm from the proton pencil beam with a satisfying precision. The root mean square error between Monte Carlo simulation and model is largest for 138 MeV protons and is 19% and 20% for dose and dose equivalent, respectively. The model was successfully integrated into the PSI treatment planning system. In average the neutron dose is increased by 10% or 65% when using 160 MeV or 177 MeV instead of 138 MeV. For the neutron dose equivalent the increase is 8% and 57%. The presented neutron dose calculations allow for estimates of dose that can be used in subsequent epidemiological studies or, should the need arise, to estimate the neutron dose at any point where a subsequent secondary tumour may occur. It was found that the neutron dose to the patient is heavily increased with proton energy.

  8. SU-E-I-33: Advances in Dose Metrics and Dose Reduction Strategies for Interventional Fluoroscopy.

    Science.gov (United States)

    Weir, V; Zhang, J; Bruner, A

    2012-06-01

    To explore recent advances in available dose metrics and dose reduction features and their impacts during various fluoroscopy procedures. Besides traditional dose metrics (cumulative dose, DAP, etc), recent methods such as real time dose mapping and dose calculation from DICOM information and their relevance to entrance skin exposure (ESE) are demonstrated. Dose reduction features and their potential effects on ESE are explored for different interventional procedures, including dose setting options, frame rate settings, wedges, software options and how these help reduce patient dose, etc. Real time dose monitoring techniques such as DoseAware are investigated. Dose alert such as flagging higher doses at about half of the Joint Commission sentinel event limit, Dose Index Registry and their impacts are discussed. Habit related practices, such as a physician leaning over patients, are highlighted, also taking foot off the fluoroscopy pedal when not needed, and best places to stand are illustrated. A practice improvement procedure involving measurement, analysis and improvement actions is instituted. We also discuss the impact of physician follow up letters to patients who might not have reached the JC Sentinel Event limits but may still have skin issues. In our institutes, these efforts have led to reduction of both patient dose and personnel exposure for interventional procedures. The recording of technical parameters and fluoroscopy dose by the staff has led to a better understanding of appropriate dose levels and technique settings for each procedure. This article can serve as a refresher for radiological staff on how to protect patients and themselves from high doses, while providing the best care possible. It can also serve as criteria for health care providers to institute changes and make quality improvement in interventional practices. © 2012 American Association of Physicists in Medicine.

  9. Dose reconstruction modeling for medical radiation workers

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yeong Chull; Cha, Eun Shil; Lee, Won Jin [Dept. of Preventive Medicine, Korea University, Seoul (Korea, Republic of)

    2017-04-15

    Exposure information is a crucial element for the assessment of health risk due to radiation. Radiation doses received by medical radiation workers have been collected and maintained by public registry since 1996. Since exposure levels in the remote past are greater concern, it is essential to reconstruct unmeasured doses in the past using known information. We developed retrodiction models for different groups of medical radiation workers and estimate individual past doses before 1996. Reconstruction models for past radiation doses received by medical radiation workers were developed, and the past doses were estimated. Using these estimates, organ doses should be calculated which, in turn, will be used to explore a wide range of health risks of medical occupational radiation exposure. Reconstruction models for past radiation doses received by medical radiation workers were developed, and the past doses were estimated. Using these estimates, organ doses should be calculated which, in turn, will be used to explore a wide range of health risks of medical occupational radiation exposure.

  10. Reduction of extremity dose in the radiopharmacy.

    Science.gov (United States)

    Mackenzie, A

    1997-06-01

    With the future introduction of legislation originating from ICRP60 in mind, the operating procedures for the radiopharmacy were reviewed, with the intention of reducing extremity radiation dose. The radiopharmacist's index fingertip dose was measured using TLDs. The radiopharmacist received a mean dose of 0.7 mSv per 10 GBq of administered activity for the right (non-dominant hand) index finger and 0.2 mSv per 10 GBq for the left (dominant hand) index finger. These doses were comparable with other publications. The radiopharmacist received the largest part of the radiation dose during the preparation of 99Tc(m)-MDP. During this preparation, the saline was withdrawn into a syringe already containing 99Tc(m)-eluate, which results in a dose to the fingers. The technique was changed so that the saline and 99Tc(m)-eluate were withdrawn and injected separately into a MDP kit. This reduced the right finger radiation dose to 0.4 mSv per 10 GBq, while the left finger radiation dose remained at 0.2 mSv per 10 GBq. This shows that radiation doses can be effectively reduced using simple changes in procedure.

  11. Hanford Environmental Dose Reconstruction Project Monthly Report

    Energy Technology Data Exchange (ETDEWEB)

    Finch, S.M. (comp.)

    1991-03-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that populations could have received from nuclear operations at Hanford since 1944. The project is being managed and conducted by the Pacific Northwest Laboratory (PNL) under the direction of an independent Technical Steering Panel (TSP). The project is divided into the technical tasks which correspond to the path radionuclides followed, from release to impact on humans (dose estimates): source terms; environmental transport; environment monitoring data; demographics, agriculture, food habits; and environmental pathways and dose estimates. 3 figs., 2 tabs.

  12. Applicability of OSL pre-dose phenomenon of quartz in the estimation of equivalent dose

    Energy Technology Data Exchange (ETDEWEB)

    Koul, D.K., E-mail: dkkoul@barc.gov.i [Astrophysical Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Chougaonkar, M.P. [Environmental Assessment Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Polymeris, G.S. [Archaeometry Laboratory, Cultural and Educational Technology Institute, R.C. ' Athena' , Tsimiski 58, GR-67100, Xanthi (Greece)

    2010-01-15

    The feasibility of utilizing the pre-dosed OSL signal in the estimation of the equivalent dose has been investigated. The results based on (i) the behavior of growth curve, (ii) dose recovery tests and (iii) non-bleachability of reservoir centres, R-centres, suggests that (i) the pre-dosed OSL does not seem to work satisfactorily in dose estimation unlike the pre-dosed 110 deg. C TL emission and (ii) it may not be applicable in case of bleached specimen.

  13. Red bone marrow doses, integral absorbed doses, and somatically effective dose equivalent from four maxillary occlusal projections.

    Science.gov (United States)

    Berge, T I; Wøhni, T

    1984-02-01

    Phantom measurements of red bone marrow (RBM) doses, integral absorbed doses, and somatically effective dose equivalent (SEDE) from four different maxillary occlusal projections are presented. For each projection, different combinations of focus-skin distances and tube potentials were compared with regard to the patient's radiation load. The axial incisal view produced the highest patient exposures, with a maximum red bone marrow dose of 122.5 microGy/exposure, integral absorbed dose of 8.6 mJ/exposure, and SEDE values of 39.6 microSv/exposure. The corresponding values from the frontal, lateral occlusal, and tuber views ranged between 4% and 44% of the axial incisal view values for the integral absorbed dose and SEDE values, and between 0.3% and 3% for the red bone marrow doses. Increasing the focus-skin distance from 17.5 cm to 27 cm is accompanied by a 24% to 30% reduction in integral absorbed dose. Increasing the tube potential from 50 kV to 65 kV likewise results in a 23% reduction in absorbed energy.

  14. Estimate Of Reference Effective Dose And Renal Dose During Abdominal CT Scan For Dose Optimization Procedures In Ghana

    Directory of Open Access Journals (Sweden)

    Issahaku Shirazu

    2015-08-01

    Full Text Available The study is to estimate renal and effective dose during abdominal MDCT scan using image data for dose optimization for purposes of radiation protection in Ghana. In addition dose influencing parameters including CTDIVOL DLP and MSAD were recorded and compared with ICRPICRU AAPM EU and IAEA dose optimization recommendations. All the measurements were done during abdominal MDCT examination. The measured parameters were part of image data on the MeVisLab DICOM application software platform. The total photon fluence mAs per area and the photon energy fluence kVp per area on the abdominal and renal surface was also determined. Renal and effective dose were estimated using ICRP publication 103 recommendations. The results of the measured parameters based on the average renal surface area of 29.52cm2 and 30.67cm2 for the right and left kidney respectively shows that The mean dose parameters were 6.33mGy 7.78mGy 936.25mGy cm 5.76mGy 10.99mSv and 14.09mSv for CTDIV CTDIW DLP MSAD RD and E respectively. The average values were lower than the general recommended average critical values but this seems misleading based on the fact that 37 of the individual dose and exposure parameters exceeded the recommended critical values. A tradeoff between patient radiation dose and image quality in abdominal CT has been established. Where at a mean SNR of 6.6 decibels an adequate images were produce to answer all the clinical questions with an average effective dose of 14.09mSv and renal dose of 10.99mSv. Radiation dose during x-ray CT imaging is an important patient safety concern. Reducing radiation dose result in a reduction of the risk to patient however reducing dose also reduces the signal strength and thereby reduces the signal to noise ratio in the resulting CT image hence the image quality is affected. It is recommended that the established reference values be use as clinical advisory mechanism to protect patience and clinicians. It is also recommended that

  15. Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

    Science.gov (United States)

    Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

    2016-04-20

    The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

  16. Dose-ranging design and analysis methods to identify the minimum effective dose (MED).

    Science.gov (United States)

    Zhou, Yijie; Chen, Su; Sullivan, Danielle; Li, Yihan; Zhang, Ying; Xie, Wangang; Zhang, Hongtao; Tang, Yuanyuan; Wang, Li; Hartford, Alan; Yang, Bo

    2017-12-01

    In dose ranging clinical trials, it is critical to investigate the dose-response profile and to identify a minimum effective dose (MED) to guide the dose selection for phase 3 confirmatory trials. Traditional dose ranging trials focus on pairwise comparisons between placebo and each investigational dose, while in recent years MCP-Mod (Multiple Comparison Procedures & Modeling) arose and gained popularity in the design and analysis of dose ranging trials. Comprehensive comparison between MCP-Mod and other methods have been made on continuous variables assuming a normal distribution. In this article, we extend the comparison to binary/binomial response variables. Via simulation, the rate of correct and incorrect MED identification are compared for Dunnett's test, trend test and MCP-Mod for a variety of underlying dose response profiles including both monotone and non-monotone dose responses and are compared under a large number of trial design settings. The precision of MED estimation using MCP-Mod is also evaluated comparing the design options of more dose levels and smaller sample size per dose versus fewer dose levels and larger sample size per dose. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Comparison of TID Effects in Space-Like Variable Dose Rates and Constant Dose Rates

    Science.gov (United States)

    Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Evans, Robin W.; Jun, Insoo

    2008-01-01

    The degradation of the LM193 dual voltage comparator has been studied at different TID dose rate profiles, including several different constant dose rates and a variable dose rate that simulates the behavior of a solar flare. A comparison of results following constant dose rate vs. variable dose rates is made to explore how well the constant dose rates used for typical part testing predict the performance during a simulated space-like mission. Testing at a constant dose rate equal to the lowest dose rate seen during the simulated flare provides an extremely conservative estimate of the overall amount of degradation. A constant dose rate equal to the average dose rate is also more conservative than the variable rate. It appears that, for this part, weighting the dose rates by the amount of total dose received at each rate (rather than the amount of time at each dose rate) results in an average rate that produces an amount of degradation that is a reasonable approximation to that received by the variable rate.

  18. Low-dose versus standard-dose CT protocol in patients with clinically suspected renal colic.

    Science.gov (United States)

    Poletti, Pierre-Alexandre; Platon, Alexandra; Rutschmann, Olivier T; Schmidlin, Franz R; Iselin, Christophe E; Becker, Christoph D

    2007-04-01

    The purpose of our study was to compare a low-dose abdominal CT protocol, delivering a dose of radiation close to the dose delivered by abdominal radiography, with standard-dose unenhanced CT in patients with suspected renal colic. One hundred twenty-five patients (87 men, 38 women; mean age, 45 years) who were admitted with suspected renal colic underwent both abdominal low-dose CT (30 mAs) and standard-dose CT (180 mAs). Low-dose CT and standard-dose CT were independently reviewed, in a delayed fashion, by two radiologists for the characterization of renal and ureteral calculi (location, size) and for indirect signs of renal colic (renal enlargement, pyeloureteral dilatation, periureteral or renal stranding). Results reported for low-dose CT, with regard to the patients' body mass indexes (BMIs), were compared with those obtained with standard-dose CT (reference standard). The presence of non-urinary tract-related disorders was also assessed. Informed consent was obtained from all patients. In patients with a BMI 3 mm. Low-dose CT was 100% sensitive and specific for depicting non-urinary tract-related disorders (n = 6). Low-dose CT achieves sensitivities and specificities close to those of standard-dose CT in assessing the diagnosis of renal colic, depicting ureteral calculi > 3 mm in patients with a BMI < 30, and correctly identifying alternative diagnoses.

  19. The use of modified single pencil beam dose kernels to improve IMRT dose calculation accuracy.

    Science.gov (United States)

    Bergman, Alanah M; Otto, Karl; Duzenli, Cheryl

    2004-12-01

    Intensity modulated radiation therapy (IMRT) is used to deliver highly conformal radiation doses to tumors while sparing nearby sensitive tissues. Discrepancies between calculated and measured dose distributions have been reported for regions of high dose gradients corresponding to complex radiation fluence patterns. For the single pencil beam convolution dose calculation algorithm, the ability to resolve areas of high dose structure is partly related to the shape of the pencil beam dose kernel (similar to how a photon detector's point spread function relates to imaging resolution). Improvements in dose calculation accuracy have been reported when the treatment planning system (TPS) is recommissioned using high-resolution measurement data as input. This study proposes to improve the dose calculation accuracy for IMRT planning by modifying clinical dose kernel shapes already present in the TPS, thus avoiding the need to reacquire higher resolution commissioning data. The in-house optimization program minimizes a cost-function based on a two-dimensional composite dose subtraction/distance-to-agreement (gamma) analysis. The final modified kernel shapes are reintroduced into the treatment planning system and improvements to the dose calcula tion accuracy for complex IMRT dose distributions evaluated. The central kernel value (radius =0 cm) has the largest effect on the dose calculation resolution and is the focus of this study.

  20. Calculation of midplane dose for total body irradiation from entrance and exit dose MOSFET measurements.

    Science.gov (United States)

    Satory, P R

    2012-03-01

    This work is the development of a MOSFET based surface in vivo dosimetry system for total body irradiation patients treated with bilateral extended SSD beams using PMMA missing tissue compensators adjacent to the patient. An empirical formula to calculate midplane dose from MOSFET measured entrance and exit doses has been derived. The dependency of surface dose on the air-gap between the spoiler and the surface was investigated by suspending a spoiler above a water phantom, and taking percentage depth dose measurements (PDD). Exit and entrances doses were measured with MOSFETs in conjunction with midplane doses measured with an ion chamber. The entrance and exit doses were combined using an exponential attenuation formula to give an estimate of midplane dose and were compared to the midplane ion chamber measurement for a range of phantom thicknesses. Having a maximum PDD at the surface simplifies the prediction of midplane dose, which is achieved by ensuring that the air gap between the compensator and the surface is less than 10 cm. The comparison of estimated midplane dose and measured midplane dose showed no dependence on phantom thickness and an average correction factor of 0.88 was found. If the missing tissue compensators are kept within 10 cm of the patient then MOSFET measurements of entrance and exit dose can predict the midplane dose for the patient.

  1. Irrigation in dose assessments models

    Energy Technology Data Exchange (ETDEWEB)

    Bergstroem, Ulla; Barkefors, Catarina [Studsvik RadWaste AB, Nykoeping (Sweden)

    2004-05-01

    SKB has carried out several safety analyses for repositories for radioactive waste, one of which was SR 97, a multi-site study concerned with a future deep bedrock repository for high-level waste. In case of future releases due to unforeseen failure of the protective multiple barrier system, radionuclides may be transported with groundwater and may reach the biosphere. Assessments of doses have to be carried out with a long-term perspective. Specific models are therefore employed to estimate consequences to man. It has been determined that the main pathway for nuclides from groundwater or surface water to soil is via irrigation. Irrigation may cause contamination of crops directly by e.g. interception or rain-splash, and indirectly via root-uptake from contaminated soil. The exposed people are in many safety assessments assumed to be self-sufficient, i.e. their food is produced locally where the concentration of radionuclides may be the highest. Irrigation therefore plays an important role when estimating consequences. The present study is therefore concerned with a more extensive analysis of the role of irrigation for possible future doses to people living in the area surrounding a repository. Current irrigation practices in Sweden are summarised, showing that vegetables and potatoes are the most common crops for irrigation. In general, however, irrigation is not so common in Sweden. The irrigation model used in the latest assessments is described. A sensitivity analysis is performed showing that, as expected, interception of irrigation water and retention on vegetation surfaces are important parameters. The parameters used to describe this are discussed. A summary is also given how irrigation is proposed to be handled in the international BIOMASS (BIOsphere Modelling and ASSessment) project and in models like TAME and BIOTRAC. Similarities and differences are pointed out. Some numerical results are presented showing that surface contamination in general gives the

  2. Multicriteria optimization of the spatial dose distribution

    Energy Technology Data Exchange (ETDEWEB)

    Schlaefer, Alexander [Medical Robotics Group, Universität zu Lübeck, Lübeck 23562, Germany and Institute of Medical Technology, Hamburg University of Technology, Hamburg 21073 (Germany); Viulet, Tiberiu [Medical Robotics Group, Universität zu Lübeck, Lübeck 23562 (Germany); Muacevic, Alexander; Fürweger, Christoph [European CyberKnife Center Munich, Munich 81377 (Germany)

    2013-12-15

    Purpose: Treatment planning for radiation therapy involves trade-offs with respect to different clinical goals. Typically, the dose distribution is evaluated based on few statistics and dose–volume histograms. Particularly for stereotactic treatments, the spatial dose distribution represents further criteria, e.g., when considering the gradient between subregions of volumes of interest. The authors have studied how to consider the spatial dose distribution using a multicriteria optimization approach.Methods: The authors have extended a stepwise multicriteria optimization approach to include criteria with respect to the local dose distribution. Based on a three-dimensional visualization of the dose the authors use a software tool allowing interaction with the dose distribution to map objectives with respect to its shape to a constrained optimization problem. Similarly, conflicting criteria are highlighted and the planner decides if and where to relax the shape of the dose distribution.Results: To demonstrate the potential of spatial multicriteria optimization, the tool was applied to a prostate and meningioma case. For the prostate case, local sparing of the rectal wall and shaping of a boost volume are a