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Sample records for acidic remineralization regimen

  1. Remineralizing agents: effects on acid-softened enamel.

    PubMed

    Porcelli, H Bp; Maeda, F A; Silva, B R; Miranda, W G; Cardoso, P Ec

    2015-01-01

    This study sought to evaluate whether remineralizing toothpastes can protect acid-softened enamel against further erosive episodes. Fifty enamel slabs of bovine teeth with preformed erosion-like lesions were randomly assigned to 1 control and 4 experimental groups (n = 10): group 1, nanohydroxyapatite (nanoHAp) dentifrice; group 2, arginine and calcium carbonate (CaCO3) dentifrice; group 3, potassium nitrate (KNO3) and high-fluoride (F) availability dentifrice; group 4, ordinary fluoridated dentifrice (OFD); and group 5, control (deionized water). Initial hardness measurements were taken after the different treatments were applied. Statistically significant mineral gains of 8.0% and 10.0% were exhibited in groups 1 and 4, respectively. Groups 2 and 3 showed mineral gains of 4.5% and 2.1%, respectively; these were not statistically significant. Group 5 showed mineral loss (-11.8%). A 1-way analysis of variance showed no statistically significant differences in the mean microhardness values among groups. However, there are indications that the nanoHAp and OFD toothpastes may decrease erosive lesions after treatment, while the arginine + CaCO3 and KNO3 + F pastes may prevent the progression of erosive lesions.

  2. Phosphoric acid esters cannot replace polyvinylphosphonic acid as phosphoprotein analogs in biomimetic remineralization of resin-bonded dentin

    PubMed Central

    Mai, Sui; Kim, Young Kyung; Toledano, Manuel; Breschi, Lorenzo; Ling, Jun Qi; Pashley, David H.; Tay, Franklin R.

    2009-01-01

    Polyvinylphosphonic acid (PVPA), a biomimetic analog of phosphoproteins, is crucial for recruiting polyacrylic acid (PAA)-stabilized amorphous calcium phosphate nanoprecursors during biomimetic remineralization of dentin collagen matrices. This study tested the null hypothesis that phosphoric acid esters of methacrylates in dentin adhesives cannot replace PVPA during bimimetic remineralization of resin-dentin interfaces. Human dentin specimens were bonded with: I) XP Bond, an etch-and-rinse adhesive using moist bonding; II) XP Bond using dry bonding; and III) Adper Prompt L-Pop, a self-etching adhesive. The control medium contained only set Portland cement and a simulated body fluid (SBF) without any biomimetic analog. Two experimental Portland cement/SBF remineralization media were evaluated: the first contained PAA as the sole biomimetic analog, the second contained PAA and PVPA as dual biomimetic analogs. No remineralization of the resin-dentin interfaces could be identified from specimens immersed in the control medium. After 2–4 months in the first experimental medium, specimens exhibited either no remineralization or large crystal formation within hybrid layers. Only specimens immersed in the second remineralization medium produced nanocrystals that accounted for intrafibrillar remineralization within hybrid layers. The null hypothesis could not be rejected; phosphoric acid esters in dentin adhesives cannot replace PVPA during biomimetic remineralization of adhesive-bonded dentin. PMID:19481792

  3. Effect of acid-etching on remineralization of enamel white spot lesions.

    PubMed

    Al-Khateeb, S; Exterkate, R; Angmar-Månsson, B; ten Cate, J M; ten Cate, B

    2000-02-01

    This in vitro study aimed at investigating whether full remineralization would occur in white spot lesions when the surface porosity was increased by acid-etching. The effect of fluoride was also investigated. Enamel blocks with in vitro produced white spot lesions were used. Group A was exposed to a remineralizing solution only. In group B, the lesions were etched with 35% phosphoric acid for 30 s, then treated as in group A. Group C was treated as group A + daily treatment with a fluoride toothpaste slurry (1,000 ppm) for 5 min. Group D was treated as group B + the daily fluoride treatment of group C. The remineralization was measured weekly with Quantitative Light-induced Fluorescence during the experimental period. After 10 weeks of remineralization, mineral profiles were assessed with transverse microradiography. The enamel fluorescence was partly regained. There were significant differences in the lesion depth, mineral content at the surface layer, and integrated mineral loss between the groups. Addition of fluoride accelerated the remineralization only in the beginning; in later stages the process leveled out and even reached a plateau in all the groups. It was concluded that full remineralization was not achieved by etching, by the addition of fluoride, nor by the combination of both treatments in this in vitro study.

  4. Remineralization of Demineralized Enamel via Calcium Phosphate Nanocomposite

    PubMed Central

    Weir, M.D.; Chow, L.C.; Xu, H.H.K.

    2012-01-01

    Secondary caries remains the main problem limiting the longevity of composite restorations. The objective of this study was to investigate the remineralization of demineralized human enamel in vitro via a nanocomposite containing nanoparticles of amorphous calcium phosphate (NACP). NACP were synthesized by a spray-drying technique and incorporated into a dental resin. First, caries-like subsurface enamel lesions were created via an acidic solution. Then, NACP nanocomposite or a commercial fluoride-releasing control composite was placed on the demineralized enamel, along with control enamel without a composite. These specimens were then treated with a cyclic demineralization/remineralization regimen for 30 days. Quantitative microradiography showed typical enamel subsurface demineralization before cyclic demineralization/remineralization treatment, and significant remineralization in enamel under the NACP nanocomposite after the demineralization/remineralization treatment. The NACP nanocomposite had the highest enamel remineralization (mean ± SD; n = 6) of 21.8 ± 3.7%, significantly higher than the 5.7 ± 6.9% for fluoride-releasing composite (p < 0.05). The enamel group without composite had further demineralization of −26.1 ± 16.2%. In conclusion, a novel NACP nanocomposite was effective in remineralizing enamel lesions in vitro. Its enamel remineralization was 4-fold that of a fluoride-releasing composite control. Combined with the good mechanical and acid-neutralization properties reported earlier, the new NACP nanocomposite is promising for remineralization of demineralized tooth structures. PMID:22933607

  5. Effect of CPP-ACP on the remineralization of acid-eroded human tooth enamel: nanomechanical properties and microtribological behaviour study

    NASA Astrophysics Data System (ADS)

    Zheng, L.; Zheng, J.; Zhang, Y. F.; Qian, L. M.; Zhou, Z. R.

    2013-10-01

    Casein phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP) has been used to enhance tooth remineralization in the dental clinic. But the contribution of CPP-ACP to the remineralization of acid-eroded human tooth enamel is of widespread controversy. To confirm the application potential of CPP-ACP in the remineralization repair of tooth erosion caused by acid-attack, the effect of remineralization in vitro in 2% w/v CPP-ACP solution on the acid-eroded human tooth enamel was investigated in this study. The repair of surface morphology and the improvement of nanomechanical and microtribological properties were characterized with laser confocal scanning microscope, scanning electron microscope, nanoindentation tester and nanoscratch tester. Results showed that a layer of uneven mineral deposits, which were mainly amorphous calcium phosphate (ACP) in all probability, was observed on the acid-eroded enamel surface after remineralization. Compared with the acid-eroded enamel surface, the nanoindentation hardness and Young's modulus of the remineralized enamel surface obviously increased. Both the friction coefficient and wear volume of the acid-eroded enamel surface decreased after remineralization. However, both the nanomechanical and the anti-wear properties of the remineralized enamel surface were still inferior to those of original enamel surface. In summary, tooth damage caused by acid erosion could be repaired by remineralization in CPP-ACP solution, but the repair effect, especially on the nanomechanical and anti-wear properties of the acid-eroded enamel, was limited. These results would contribute to a further exploration of the remineralization potential of CPP-ACP and a better understanding of the remineralization repair mechanism for acid-eroded human tooth enamel.

  6. In vitro remineralization of acid-etched human enamel with Ca 3SiO 5

    NASA Astrophysics Data System (ADS)

    Dong, Zhihong; Chang, Jiang; Deng, Yan; Joiner, Andrew

    2010-02-01

    Bioactive and inductive silicate-based bioceramics play an important role in hard tissue prosthetics such as bone and teeth. In the present study, a model was established to study the acid-etched enamel remineralization with tricalcium silicate (Ca 3SiO 5, C 3S) paste in vitro. After soaking in simulated oral fluid (SOF), Ca-P precipitation layer was formed on the enamel surface, with the prolonged soaking time, apatite layer turned into density and uniformity and thickness increasingly from 250 to 350 nm for 1 day to 1.7-1.9 μm for 7 days. Structure of apatite crystals was similar to that of hydroxyapatite (HAp). At the same time, surface smoothness of the remineralized layer is favorable for the oral hygiene. These results suggested that C 3S treated the acid-etched enamel can induce apatite formation, indicating the biomimic mineralization ability, and C 3S could be used as an agent of inductive biomineralization for the enamel prosthesis and protection.

  7. Biomimetic remineralization of dentin

    PubMed Central

    Niu, Li-na; Zhang, Wei; Pashley, David H.; Breschi, Lorenzo; Mao, Jing; Chen, Ji-hua; Tay, Franklin R.

    2013-01-01

    Objectives Remineralization of demineralized dentin is important for improving dentin bonding stability and controlling primary and secondary caries. Nevertheless, conventional dentin remineralization strategy is not suitable for remineralizing completely-demineralized dentin within hybrid layers created by etch-and-rinse and moderately aggressive self-etch adhesive systems, or the superficial part of a caries-affected dentin lesion left behind after minimally invasive caries removal. Biomimetic remineralization represents a different approach to this problem by attempting to backfill the demineralized dentin collagen with liquid-like amorphous calcium phosphate nanoprecursor particles that are stabilized by biomimetic analogs of noncollagenous proteins. Methods This paper reviewed the changing concepts in calcium phosphate mineralization of fibrillar collagen, including the recently discovered, non-classical particle-based crystallization concept, formation of polymer-induced liquid- precursors (PILP), experimental collagen models for mineralization, and the need for using phosphate-containing biomimetic analogs for biomimetic mineralization of collagen. Published work on the remineralization of resin-dentin bonds and artificial caries-like lesions by various research groups was then reviewed. Finally, the problems and progress associated with the translation of a scientifically-sound concept into a clinically-applicable approach are discussed. Results and Significance The particle-based biomimetic remineralization strategy based on the PILP process demonstrates great potential in remineralizing faulty hybrid layers or caries-like dentin. Based on this concept, research in the development of more clinically feasible dentin remineralization strategy, such as incorporating poly(anionic) acid-stabilized amorphous calcium phosphate nanoprecursor-containing mesoporous silica nanofillers in dentin adhesives, may provide a promising strategy for increasing of the

  8. Poly (amido amine) and nano-calcium phosphate bonding agent to remineralize tooth dentin in cyclic artificial saliva/lactic acid.

    PubMed

    Liang, Kunneng; Weir, Michael D; Reynolds, Mark A; Zhou, Xuedong; Li, Jiyao; Xu, Hockin H K

    2017-03-01

    The objectives of this study were to develop a novel method to remineralize dentin lesions, and investigate the remineralization effects of poly (amido amine) (PAMAM) dendrimer plus a bonding agent with nanoparticles of amorphous calcium phosphate (NACP) in a cyclic artificial saliva/lactic acid environment for the first time. Dentin lesions were produced via phosphoric acid. Four groups were tested: (1) dentin control, (2) dentin with PAMAM, (3) dentin with NACP bonding agent, and (4) dentin with PAMAM plus NACP bonding agent. Specimens were treated with cyclic artificial saliva/lactic acid. The remineralized dentin was examined using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), hardness and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). NACP bonding agent yielded a dentin shear bond strength similar to commercial controls (Prime & Bond NT, Dentsply; Scotchbond Multi-purpose, 3M) (p>0.1). Increasing NACP in bonding agent from 0 to 40% did not affect bond strength. NACP bonding agent neutralized the acid and released Ca ions with concentrations of 4 to 20mmol/L, and P ions of 2 to 9mmol/L. PAMAM or NACP bonding agent alone achieved slight remineralization. The PAMAM+NACP group achieved the greatest dentin remineralization p<0.05). At 20days, PAMAM+NACP increased the hardness of pre-demineralized dentin to reach the normal dentin hardness (p>0.1). In conclusion, superior remineralization of PAMAM+NACP bonding agent was demonstrated for the first time. PAMAM+NACP bonding agent induced dentin remineralization under acid challenge, when conventional remineralization methods such as PAMAM alone did not work well. The novel PAMAM+NACP bonding agent method is promising to improve the longevity of resin-dentin bonds, inhibit caries, and protect teeth.

  9. Polydopamine-induced tooth remineralization.

    PubMed

    Zhou, Yun-Zhi; Cao, Ying; Liu, Wei; Chu, Chun Hung; Li, Quan-Li

    2012-12-01

    Inspired by mussel bioadhesion in nature, dopamine is extensively used for biomaterial surface modification. In this study, we coated dopamine on demineralized enamel and dentin surfaces to evaluate the effect of polydopamine coating on dental remineralization. Dental slices containing enamel and dentin were first etched with 37% phosphoric acid for 2 min, followed by immersion in a 2 mg/mL freshly prepared solution of dopamine (10 mM Tris buffer, pH 8.5) for approximately 24 h at room temperature in the dark to obtain polydopamine coating. Then, the dental slices with and without polydopamine coating were immersed in the supersaturated solution of calcium and phosphate at 37 °C for 2 and 7 days. The supersaturated solution of calcium and phosphate was refreshed each day. The precipitates were characterized by SEM, XRD, FTIR, microhardness, and nanoscratch analyses. No significant difference was observed in the remineralization of enamel whether it was coated with polydopamine or not. However, a significant difference was found in dentin remineralization between dentin with and without polydopamine coating. Polydopamine coating remarkably promoted demineralized dentin remineralization, and all dentin tubules were occluded by densely packed hydroxyapatite crystals. Thus, coating polydopamine on dental tissue surface may be a simple universal technique to induce enamel and dentin remineralization simultaneously.

  10. In situ remineralization of subsurface enamel lesion after the use of a fluoride chewing gum.

    PubMed

    Lamb, W J; Corpron, R E; More, F G; Beltran, E D; Strachan, D S; Kowalski, C J

    1993-01-01

    In situ remineralization of early enamel lesions by a fluoride chewing gum was studied. Human enamel specimens with subsurface lesions were mounted in removable lower appliances for 6 adults. Subjects used a F-free dentifrice 3x/day and chewed five sticks/day for the F gum group (0.1 mg F/stick) or five sticks of sugarless gum. No gum was chewed for controls. Surface microhardness was performed on: (1) sound enamel; (2) lesions; (3) after intraoral exposure, and (4) after acid-resistance testing (ART). Separate specimens were etched and measured for F uptake and image analyses on microradiographs were performed for all regimens. delta Z values were calculated and converted to percent of mineralization. Values for F gum were significantly higher (p > 0.05) than non-F gum and controls for ART, percent remineralization, and F uptake up to 70 microns depth.

  11. Dose-response effects of zinc and fluoride on caries lesion remineralization.

    PubMed

    Lippert, F

    2012-01-01

    The present mechanistic in vitro study aimed to investigate dose-response effects of zinc and fluoride on caries lesion remineralization and subsequent protection from demineralization. Artificial caries lesions were created using a methylcellulose acid gel system. Lesions were remineralized for 2 weeks using citrate-containing artificial saliva which was supplemented with zinc (0-153 μmol/l) and fluoride (1.1 or 52.6 μmol/l) in a 7 × 2 factorial design. Lesions were also remineralized in the absence of zinc and citrate, but in the presence of fluoride. After remineralization, all lesions were demineralized for 1 day under identical conditions. Changes in mineral distribution characteristics of caries lesions after remineralization and secondary demineralization were studied using transverse microradiography. At 1.1 μmol/l fluoride, zinc exhibited detrimental effects on remineralization in a dose-response manner and mainly by preventing remineralization near the lesion surface. At 52.6 μmol/l fluoride, zinc retarded remineralization only at the highest concentration tested. Zinc enhanced overall remineralization at 3.8-15.3 μmol/l. At 76.5 and less so at 153 μmol/l, zinc showed extensive remineralization of deeper parts within the lesions at the expense of remineralization near the surface. Citrate did not interfere with remineralization at 1.1 μmol/l fluoride, but enhanced remineralization at 52.6 μmol/l fluoride. Lesions exhibiting preferential remineralization in deeper parts showed higher mineral loss after secondary demineralization, suggesting the formation of more soluble mineral phases during remineralization. In summary, zinc and fluoride showed synergistic effects in enhancing lesion remineralization, however only at elevated fluoride concentrations.

  12. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    SciTech Connect

    Van Beneden, Katrien; Geers, Caroline; Pauwels, Marina; Mannaerts, Inge; Wissing, Karl M.; Van den Branden, Christiane; Grunsven, Leo A. van

    2013-09-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.

  13. Remineralization of artificial dentinal caries lesions by biomimetically modified Mineral Trioxide Aggregate

    PubMed Central

    Qi, Yi-pin; Li, Nan; Niu, Li-na; Primus, Carolyn M.; Ling, Jun-Qi; Pashley, David H.; Tay, Franklin R.

    2011-01-01

    Fluoride-releasing restorative materials are available for remineralization of enamel and root caries. However, dentin remineralization is more difficult than enamel remineralization due to the paucity of apatite seed crystallites along the lesion surface for heterogeneous crystal growth. Extracellular matrix proteins play critical roles in controlling apatite nucleation/growth in collagenous tissues. This study examined the remineralization efficacy of mineral trioxide aggregate (MTA) in phosphate-containing simulated body fluid (SBF) by incorporating polyacrylic acid and sodium tripolyphosphate as biomimetic analogs of matrix proteins for remineralizing caries-like dentin. Artificial caries-like dentin lesions incubated in SBF were remineralized over a 6-week period using MTA or MTA containing biomimetic analogs in the absence or presence of dentin adhesive application. Lesion depths and integrated mineral loss were monitored with micro-computed tomography. Ultrastructure of baseline and remineralized lesions were examined by transmission electron microscopy. Dentin remineralization was best achieved using MTA containing biomimetic analogs regardless of whether an adhesive was applied; dentinal tubules within the remineralized dentin were occluded by apatite. It is concluded that the MTA version employed in the study may be doped with biomimetic analogs for remineralization of unbonded and bonded artificial caries-like lesions in the presence of SBF. PMID:22085925

  14. Effect of modification of the kilning regimen on levels of free ferulic acid and antioxidant activity in malt.

    PubMed

    Inns, Elizabeth L; Buggey, Lesley A; Booer, Christopher; Nursten, Harry E; Ames, Jennifer M

    2011-09-14

    Barley phenolic antioxidants change in response to the kilning regimen used to prepare malt. Green malt was kilned using four different regimens. There were no major differences among the finished malts in parameters routinely used by the malting industry, including, moisture, color, and diastatic activity. Ferulic acid esterase activity and free ferulic acid were higher in malts subjected to the coolest kilning regimen, but malt ethyl acetate extracts (containing ferulic acid) contributed only ∼5% of the total malt antioxidant activity. Finished malt from the hottest kilning regimen possessed the highest antioxidant activity, attributed to higher levels of Maillard reaction products. Modifying kilning conditions leads to changes in release of bound ferulic acid and antioxidant activity with potential beneficial effects on flavor stability in malt and beer.

  15. Acid demineralization susceptibility of dental enamel submitted to different bleaching techniques and fluoridation regimens.

    PubMed

    Salomão, Dlf; Santos, Dm; Nogueira, Rd; Palma-Dibb, Rg; Geraldo-Martins, Vr

    2014-01-01

    The aim of the current study was to assess the acid demineralization susceptibility of bleached dental enamel submitted to different fluoride regimens. One hundred bovine enamel blocks (6×6×3 mm) were randomly divided into 10 groups (n=10). Groups 1 and 2 received no bleaching. Groups 3 to 6 were submitted to an at-home bleaching technique using 6% hydrogen peroxide (HP; G3 and G4) or 10% carbamide peroxide (CP; G5 and G6). Groups 7 to 10 were submitted to an in-office bleaching technique using 35% HP (G7 and G8) or 35% CP (G9 and G10). During bleaching, a daily fluoridation regimen of 0.05% sodium fluoride (NaF) solution was performed on groups 3, 5, 7, and 9, while weekly fluoridation with a 2% NaF gel was performed on groups 4, 6, 8, and 10. The samples in groups 2 to 10 were pH cycled for 14 consecutive days. The samples from all groups were then assessed by cross-sectional Knoop microhardness at different depths from the outer enamel surface. The average Knoop hardness numbers (KHNs) were compared using one-way analysis of variance and Tukey tests (α=0.05). The comparison between groups 1 and 2 showed that the demineralization method was effective. The comparison among groups 2 to 6 showed the same susceptibility to acid demineralization, regardless of the fluoridation method used. However, the samples from groups 8 and 10 showed more susceptibility to acid demineralization when compared with group 2 (p<0.05). Groups 7 and 9 provided similar results to group 2, but the results of those groups were different when compared with groups 8 and 10. The use of 6% HP and 10% CP associated with daily or weekly fluoridation regimens did not increase the susceptibility of enamel to acid demineralization. However, the use of 35% HP and 35% CP must be associated with a daily fluoridation regimen, otherwise the in-office bleaching makes the bleached enamel more susceptible to acid demineralization.

  16. Evaluation of hippuric acid content in goat milk as a marker of feeding regimen.

    PubMed

    Carpio, A; Bonilla-Valverde, D; Arce, C; Rodríguez-Estévez, V; Sánchez-Rodríguez, M; Arce, L; Valcárcel, M

    2013-09-01

    Organic producers, traders, and consumers must address 2 issues related to milk: authentication of the production system and nutritional differentiation. The presence of hippuric acid (HA) in goat milk samples has been proposed as a possible marker to differentiate the feeding regimen of goats. The objective of this work is to check the hypothesis that HA could be a marker for the type of feeding regimen of goats by studying the influence of production system (conventional or organic) and feeding regimen (with or without grazing fodder). With this purpose, commercial cow and goat milk samples (n=27) and raw goat milk samples (n=185; collected from different breeds, localizations, and dates) were analyzed. Samples were grouped according to breed, feeding regimen, production system, and origin to compare HA content by ANOVA and honestly significant difference Tukey test at a confidence level of ≥95%. Hippuric acid content was obtained by analyzing milk samples with capillary electrophoresis. This method was validated by analyzing part of the samples with HPLC as a reference technique. Sixty-nine raw goat milk samples (of the total 158 samples analyzed in this work) were quantified by capillary electrophoresis. In these samples, the lowest average content for HA was 7±3 mg/L. This value corresponds to a group of conventional raw milk samples from goats fed with compound feed. The highest value of this group was 28±10 mg/L, corresponding to goats fed compound feed plus grass. Conversely, for organic raw goat milk samples, the highest concentration was 67±14 mg/L, which corresponds to goats fed grass. By contrast, the lowest value of this organic group was 26±10 mg/L, which belongs to goats fed organic compounds. Notice that the highest HA average content was found in samples from grazing animals corresponding to the organic group. This result suggests that HA is a good marker to determine the type of goats feeding regimen; a high content of HA represents a diet

  17. Comparison between intravenous and intra-articular regimens of tranexamic acid in reducing blood loss during total knee arthroplasty.

    PubMed

    Soni, Ashwani; Saini, Raghav; Gulati, Anmol; Paul, Rajesh; Bhatty, Shiraj; Rajoli, Sreekanth Reddy

    2014-08-01

    Tranexamic acid is an antifibrinolytic drug used widely to prevent bleeding. Its use in reducing bleeding during total knee arthroplasty surgery is well proven but there is no final consensus regarding the regimen. The purpose of our study was to compare the effectiveness of intravenous and intra-articular regimen of tranexamic acid during the total knee arthroplasty surgery. A total of 40 patients were received three doses of intravenous tranexamic acid during total knee arthroplasty surgery. Intra-articular tranexamic acid was used in 40 patients during the surgery. We concluded that intra-articular tranexamic acid is equally effective as three dose intravenous regimen in reducing blood loss during total knee arthroplasty surgery.

  18. Valproic acid improves second-line regimen of small cell lung carcinoma in preclinical models

    PubMed Central

    Hubaux, Roland; Vandermeers, Fabian; Cosse, Jean-Philippe; Crisanti, Cecilia; Kapoor, Veena; Albelda, Steven M.; Mascaux, Céline; Delvenne, Philippe; Hubert, Pascale

    2015-01-01

    With 5-year survival rates below 5%, small cell lung carcinoma (SCLC) has very poor prognosis and requires improved therapies. Despite an excellent overall response to first-line therapy, relapses are frequent and further treatments are disappointing. The goal of the study was to improve second-line therapy of SCLC. The effect of chemotherapeutic agents was evaluated in cell lines (apoptosis, reactive oxygen species, and RNA and protein expression) and in mouse models (tumour development). We demonstrate here that valproic acid, a histone deacetylase inhibitor, improves the efficacy of a second-line regimen (vindesine, doxorubicin and cyclophosphamide) in SCLC cells and in mouse models. Transcriptomic profiling integrating microRNA and mRNA data identifies key signalling pathways in the response of SCLC cells to valproic acid, opening new prospects for improved therapies. PMID:27730151

  19. Zinc induces apatite and scholzite formation during dentin remineralization.

    PubMed

    Osorio, R; Osorio, E; Cabello, I; Toledano, M

    2014-01-01

    The aim of this study was to ascertain whether zinc may improve the repair ability of demineralized dentin. Dentin disks were demineralized by phosphoric acid during 15 s and immersed in artificial saliva, remineralizing solution, a zinc chloride solution and a zinc oxide solution. Dentin specimens were analyzed after 24 h and 1 month of storage. Surface morphology was assessed by atomic force and scanning electron microscopy, mechanical properties were analyzed by nanohardness testing in a TriboIndenter, and chemical changes at the surfaces were determined by X-ray diffraction, Raman and energy-dispersive elemental analyses. After phosphoric acid application, dentin was only partially demineralized. Demineralized dentin was remineralized after 24 h of storage in any of the tested solutions (nanohardness increased and hydroxylapatite formation was detected by Raman). Remineralization was maintained up to 1 month in dentin stored in remineralizing solution, zinc chloride and zinc oxide. Zinc and phosphate were important for hydroxylapatite homeostasis. Scholzite formation was encountered in dentin stored in zinc-containing solutions. Zinc might allow to reach the balance between dentin demineralization and remineralization processes.

  20. Combining CPP-ACP with fluoride: a synergistic remineralization potential of artificially demineralized enamel or not?

    NASA Astrophysics Data System (ADS)

    El-Sayad, I. I.; Sakr, A. K.; Badr, Y. A.

    2008-08-01

    Background and objective: Minimal intervention dentistry (MID) calls for early detection and remineralization of initial demineralization. Laser fluorescence is efficient in detecting changes in mineral tooth content. Recaldent is a product of casein phosphopeptide-amorphous calcium phosphate (CPP- ACP) which delivers calcium and phosphate ions to enamel. A new product which also contains fluoride is launched in United States. The remineralizing potential of CPP- ACP per se, or when combined with 0.22% Fl supplied in an oral care gel on artificially demineralised enamel using laser fluorescence was investigated. Methods: Fifteen sound human molars were selected. Mesial surfaces were tested using He-Cd laser beam at 441.5nm with 18mW power as excitation source on a suitable set-up based on Spex 750 M monochromator provided with PMT for detection of collected auto-fluorescence from sound enamel. Mesial surfaces were subjected to demineralization for ten days. The spectra from demineralized enamel were measured. Teeth were then divided according to the remineralizing regimen into three groups: group I recaldent per se, group II recaldent combined with fluoride gel and group III artificial saliva as a positive control. After following these protocols for three weeks, the spectra from remineralized enamel from the three groups were measured. The spectra of enamel auto-fluorescence were recorded and normalized to peak intensity at about 540 nm to compare between spectra from sound, demineralized and remineralized enamel surfaces. Results: A slight red shift was noticed in spectra from demineralized enamel, while a blue shift may occur in remineralized enamel. Group II showed the highest remineralizing potential. Conclusions: Combining fluoride with CPP-ACP had a synergistic effect on enamel remineralization. In addition, laser auto-fluorescence is an accurate technique for assessment of changes in tooth enamel minerals.

  1. Can Caries-Affected Dentin be Completely Remineralized by Guided Tissue Remineralization?

    PubMed Central

    Dai, Lin; Liu, Yan; Salameh, Ziad; Khan, Sara; Mao, Jing; Pashley, David H.; Tay, Franklin R.

    2011-01-01

    Introduction To date, there is no evidence that conventional remineralization techniques using calcium and phosphate ion- containing media will completely remineralize carious lesions in regions where remnant apatite seed crystallites are absent. Conversely, guided tissue remineralization using biomimetic analogs of dentin matrix proteins is successful in remineralizing thin layers of completely demineralized dentin. The hypothesis Conventional remineralization strategy depends on epitaxial growth over existing apatite crystallites. If there are no or few crystallites, there will be no remineralization. Guided tissue remineralization uses biomimetic analogs of dentin matrix proteins to introduce sequestered amorphous calcium phosphate nanoprecursors into the internal water compartments of collagen fibrils. Attachment of templating analogs of matrix phosphoproteins to the collagen fibrils further guided the nucleation and growth of apatite crystallites within the fibril. Such a strategy is independent of apatite seed crystallites. Our hypothesis is that 250–300 microns thick artificial carious lesions can be completely remineralized in vitro by guide tissue remineralization but not by conventional remineralization techniques. Evaluation of the hypothesis Validation of the hypothesis will address the critical barrier to progress in remineralization of caries- affected dentin and shift existing paradigms by providing a novel method of remineralization based on a nanotechnology-based bottom-up approach. This will also generate important information to support the translation of the proof-of-concept biomimetic strategy into a clinically-relevant delivery system for remineralizing caries-affected dentin created by micro-organisms in the oral cavity. PMID:21909477

  2. The effect of different dose regimens of tranexamic acid in reducing blood loss during hip surgery

    PubMed Central

    Thipparampall, Anil Kumar; Gurajala, Indira; Gopinath, R

    2017-01-01

    Background and Aims: Antifibrinolytics may help bleeding in orthopaedic surgeries. The present study was undertaken to compare two dose regimens of tranexamic acid (TA) on perioperative blood loss in patients undergoing hip surgeries. Methods: In a prospective, randomised, controlled study, 59 patients scheduled for hip surgery were divided into Group C: receiving normal saline (n – 20), Group B: receiving single dose of TA (10 mg/kg) (n – 21), and Group I: receiving a bolus (10 mg/kg) plus infusion (1 mg/kg/h) of TA up to 4 h postoperatively (n – 18). Blood loss, haemoglobin and allogeneic blood transfusions were compared between the groups. For parametric data, P was calculated by ANOVA. Intergroup comparison was done by post hoc analysis with Bonferroni test. P < 0.05 was considered significant. Results: The intra-operative blood loss was lower in the patients who received TA (525 ± 150, 456 ± 156 and 400 ± 133 ml in Group C, B and I respectively; P = 0.05). The 6th hourly drain collection in Group I was lower than Group B and C (41 ± 18, 46 ± 14 and 31 ± 14 ml in Group C, B, and I respectively; P = 0.018). The blood loss at 24 h was less in groups receiving TA (146 ± 32, 120 ± 76, 107 ± 37 ml for Group C, B and I, respectively; P = 0.02). The requirement of blood transfusions was lower in Group I. Conclusions: A bolus of tranexamic acid followed by infusion is more useful than a single dose in decreasing perioperative blood loss in patients undergoing hip surgeries. It reduces allogenic blood transfusion without increasing risk of thromboembolic events.

  3. An in vitro study of the microstructure, composition and nanoindentation mechanical properties of remineralizing human dental enamel

    NASA Astrophysics Data System (ADS)

    Arsecularatne, J. A.; Hoffman, M.

    2014-08-01

    This paper describes the results of an in vitro investigation on the interrelations among microstructure, composition and mechanical properties of remineralizing human dental enamel. Polished enamel samples have been demineralized for 10 min in an acetic acid solution (at pH 3) followed by remineralization in human saliva for 30 and 120 min. Microstructure variations of sound, demineralized and remineralized enamel samples have been analysed using focused ion beam, scanning electron microscopy and transmission electron microscopy, while their compositions have been analysed using energy dispersive x-ray. Variations in the mechanical properties of enamel samples have been assessed using nanoindentation. The results reveal that, under the selected conditions, only partial remineralization of the softened enamel surface layer occurs where some pores remain unrepaired. As a result, while the nanoindentation elastic modulus shows an improvement following remineralization, hardness does not.

  4. Fluorides and non-fluoride remineralization systems.

    PubMed

    Amaechi, Bennett T; van Loveren, Cor

    2013-01-01

    Caries develops when the equilibrium between de- and remineralization is unbalanced favoring demineralization. De- and remineralization occur depending on the degree of saturation of the interstitial fluids with respect to the tooth mineral. This equilibrium is positively influenced when fluoride, calcium and phosphate ions are added favoring remineralization. In addition, when fluoride is present, it will be incorporated into the newly formed mineral which is then less soluble. Toothpastes may contain fluoride and calcium ions separately or together in various compounds (remineralization systems) and may therefore reduce demineralization and promote remineralization. Formulating all these compounds in one paste may be challenging due to possible premature calcium-fluoride interactions and the low solubility of CaF2. There is a large amount of clinical evidence supporting the potent caries preventive effect of fluoride toothpastes indisputably. The amount of clinical evidence of the effectiveness of the other remineralization systems is far less convincing. Evidence is lacking for head to head comparisons of the various remineralization systems.

  5. Remineralization of caries lesions extending into dentin.

    PubMed

    ten Cate, J M

    2001-05-01

    Remineralization is one aspect of the overall process of tooth decay. However, it is primarily studied in shallow lesions. The aim of this study was to explore whether caries lesions in enamel and extending into the dentin can be remineralized. A single-section model was developed for the longitudinal and non-destructive monitoring of changes in enamel and dentin. Lesions at least 200 microm into dentin were formed in undersaturated acetate buffers. Next, the lesions were divided into groups (three treatment and one control) and remineralized. The treatments were: weekly immersion in 1,000 ppm fluoride, single treatment with methanehydroxybisphosphonate, and a constant level of 1 ppm fluoride. De- and remineralization was assessed by transverse microradiography. Remineralization was observed in enamel, but also in dentin, indicating that, deep into dentin, the pores become supersaturated to apatite formation. Treatments affected remineralization only in the outer part of enamel. Both findings are explained by a relatively fast diffusion of mineral ions, with precipitation being rate-limiting. The results suggest that dentin remineralization, underneath enamel, can be achieved and could possibly be used in clinical treatment strategies.

  6. Variations in conjugated linoleic acid (CLA) content of processed cheese by lactation time, feeding regimen, and ripening.

    PubMed

    Kim, Jun Ho; Kwon, O-Jun; Choi, Nag-Jin; Oh, Se Jong; Jeong, Ha-Yeon; Song, Man-Kang; Jeong, Inhye; Kim, Young Jun

    2009-04-22

    Dairy products are major sources of conjugated linoleic acid (CLA); thus, an increase in CLA content can improve the quality value of dairy products. The objective of this work was to determine the effects of lactation time, feeding regimen, and ripening period on the level of CLA in processed cheese. CLA content in milk varied with the period of lactation; high in spring (April and May, about 6.8 mg CLA/g fat) and relatively low in mid summer and winter (about 4.3 mg CLA/g fat). The effects of dietary regimen and ripening period were determined in milk, which was obtained from March to May. After aging for 4 months, the cheese made from milk obtained from cows fed on pasture contained relatively higher levels of CLA compared to cheese made from milk obtained from cows fed indoors (8.12 mg CLA/g fat vs 6.76 mg CLA/g fat), but there was no difference in 7 month-aged cheeses. In both pasture and indoor feeding, 7 month-aged cheeses showed higher CLA content than 4 month-aged cheeses. The contents of stearic acid (C18:0) and linolenic acid (C18:3) were significantly higher in cheese from pasture fed cows compared to those in cows fed indoors. These findings should be helpful for the efficient production of functional dairy products with high CLA contents.

  7. Assessment of remineralized dentin lesions with thermal and near-infrared reflectance imaging

    NASA Astrophysics Data System (ADS)

    Lee, Robert C.; Darling, Cynthia L.; Fried, Daniel

    2016-02-01

    Accurate detection and measurement of the highly mineralized surface layer that forms on caries lesions is important for the diagnosis of lesion activity. Previous studies have demonstrated that optical imaging methods can be used to measure the degree of remineralization on enamel lesions. The purpose of this study was to determine if thermal and near-IR reflectance imaging could be used to assess the remineralization process in simulated dentin lesions. Artificial bovine (n=15) dentin lesions were prepared by immersion in a demineralization solution for 24 hours and they were subsequently placed in an acidic remineralization solution for up to 12 days. The samples were dehydrated using an air spray for 30 seconds and imaged using thermal and InGaAs cameras. The area enclosed by the time-temperature curve, ΔQ, from thermal imaging decreased significantly with longer periods of remineralization. However, near-IR reflectance intensity differences, ΔI, before and after dehydration failed to show any significant relationship with the degree of remineralization. This study shows that thermal imaging can be used for the assessment of the remineralization of dentin lesions.

  8. Assessment of remineralized dentin lesions with thermal and near-infrared reflectance imaging

    PubMed Central

    Lee, Robert C.; Darling, Cynthia L.; Fried, Daniel

    2016-01-01

    Accurate detection and measurement of the highly mineralized surface layer that forms on caries lesions is important for the diagnosis of lesion activity. Previous studies have demonstrated that optical imaging methods can be used to measure the degree of remineralization on enamel lesions. The purpose of this study was to determine if thermal and near-IR reflectance imaging could be used to assess the remineralization process in simulated dentin lesions. Artificial bovine (n=15) dentin lesions were prepared by immersion in a demineralization solution for 24 hours and they were subsequently placed in an acidic remineralization solution for up to 12 days. The samples were dehydrated using an air spray for 30 seconds and imaged using thermal and InGaAs cameras. The area enclosed by the time-temperature curve, ΔQ, from thermal imaging decreased significantly with longer periods of remineralization. However, near-IR reflectance intensity differences, ΔI, before and after dehydration failed to show any significant relationship with the degree of remineralization. This study shows that thermal imaging can be used for the assessment of the remineralization of dentin lesions. PMID:27006522

  9. Enamel demineralization and remineralization under plaque fluid-like conditions: a quantitative light-induced fluorescence study.

    PubMed

    Lippert, F; Butler, A; Lynch, R J M

    2011-01-01

    The present study investigated de- and remineralization in enamel lesions under plaque fluid (PF)-like conditions using quantitative light-induced fluorescence (QLF). Preformed lesions were exposed to partially saturated lactic acid solutions, varying in pH and fluoride concentration ([F]) based on a 5 × 3 factorial study design (0/0.1/0.5/1.5/4 ppm F; pH 4.9/5.2/5.5). Average fluorescence loss (ΔF) was monitored for 11 days. Subsequently, lesions were demineralized in a partially saturated acetic acid solution for two 24-hour periods. Data were analyzed using repeated measures analysis of covariance. Lesions exposed to PF at 4 ppm F and pH 5.5 showed not only the most remineralization (ΔΔF = 28.2 ± 14.0%) for all groups after 11 days, but also the most demineralization (ΔΔF = -19.3 ± 13.5%) after subsequent acetic acid exposure. Increased [F] resulted in more remineralization, regardless of pH. Higher pH values resulted in more remineralization. No remineralization was observed in lesions exposed to F-free solutions, regardless of pH. Remineralization was noticeable under the following conditions: pH 4.9 - [F] = 4 ppm, pH 5.2 - [F] ≥ 1.5 ppm, and pH 5.5 - [F] ≥ 0.5 ppm. Overall, [F] had a stronger effect on remineralization than pH. Subsequent demineralization showed that little protection was offered by PF-like solutions, and further demineralization compared with baseline was observed on lesions not remineralized initially. [F] had a stronger effect on net mineral change than pH. The present study has shown that QLF is a valuable tool in studying lesion de- and remineralization under PF-like conditions, where [F] was shown to be more important than pH.

  10. A sequential treatment regimen with melatonin and all-trans retinoic acid induces apoptosis in MCF-7 tumour cells.

    PubMed Central

    Eck, K. M.; Yuan, L.; Duffy, L.; Ram, P. T.; Ayettey, S.; Chen, I.; Cohn, C. S.; Reed, J. C.; Hill, S. M.

    1998-01-01

    Neoplastic events are marked by uncontrolled cell proliferation. One major focus of cancer research has been to identify treatments that reduce or inhibit cell growth. Over the years, various compounds, both naturally occurring and chemically synthesized, have been used to inhibit neoplastic cell proliferation. Two such oncostatic agents, melatonin and retinoic acid, have been shown to suppress the growth of hormone-responsive breast cancer. Currently, separate clinical protocols exist for the administration of retinoids and melatonin as adjuvant therapies for cancer. Using the oestrogen receptor (ER)-positive MCF-7 human breast tumour cell line, our laboratory has studied the effects of a sequential treatment regimen of melatonin followed by all-trans retinoic acid (atRA) on breast tumour cell proliferation in vitro. Incubation of hormonally responsive MCF-7 and T47D cells with melatonin (10(-9) M) followed 24 h later by atRA (10(-9) M) resulted in the complete cessation of cell growth as well as a reduction in the number of cells to below the initial plating density. This cytocidal effect is in contrast to the growth-suppressive effects seen with either hormone alone. This regimen of melatonin followed by atRA induced cytocidal effects on MCF-7 cells by activating pathways leading to apoptosis (programmed cell death) as evidenced by decreased ER and Bcl-2 and increased Bax and transforming growth factor beta 1 (TGF-beta1) expression. Apoptosis was reflected morphologically by an increase in the number of lysosomal bodies and perinuclear chromatin condensation, cytoplasmic blebbing and the presence of apoptotic bodies. The apoptotic effect of this sequential treatment with melatonin and atRA appears to be both cell and regimen specific as (a) ER-negative MDA-MB-231 and BT-20 breast tumour cells were unaffected, and (b) the simultaneous administration of melatonin and atRA was not associated with apoptosis in any of the breast cancer cell lines studied. Taken

  11. Nanotechnology strategies for antibacterial and remineralizing composites and adhesives to tackle dental caries.

    PubMed

    Cheng, Lei; Zhang, Ke; Weir, Michael D; Melo, Mary Anne S; Zhou, Xuedong; Xu, Hockin H K

    2015-03-01

    Dental caries is the most widespread disease and an economic burden. Nanotechnology is promising to inhibit caries by controlling biofilm acids and enhancing remineralization. Nanoparticles of silver were incorporated into composites/adhesives, along with quaternary ammonium methacrylates (QAMs), to combat biofilms. Nanoparticles of amorphous calcium phosphate (NACP) released calcium/phosphate ions, remineralized tooth-lesions and neutralized acids. By combining nanoparticles of silver/QAM/NACP, a new class of composites and adhesives with antibacterial and remineralization double benefits was developed. Various other nanoparticles including metal and oxide nanoparticles such as ZnO and TiO2, as well as polyethylenimine nanoparticles and their antibacterial capabilities in dental resins were also reviewed. These nanoparticles are promising for incorporation into dental composites/cements/sealants/bases/liners/adhesives. Therefore, nanotechnology has potential to significantly improve restorative and preventive dentistry.

  12. Nanotechnology strategies for antibacterial and remineralizing composites and adhesives to tackle dental caries

    PubMed Central

    Cheng, Lei; Zhang, Ke; Weir, Michael D; Melo, Mary Anne S; Zhou, Xuedong; Xu, Hockin HK

    2015-01-01

    Dental caries is the most widespread disease and an economic burden. Nanotechnology is promising to inhibit caries by controlling biofilm acids and enhancing remineralization. Nanoparticles of silver were incorporated into composites/adhesives, along with quaternary ammonium methacrylates (QAMs), to combat biofilms. Nanoparticles of amorphous calcium phosphate (NACP) released calcium/phosphate ions, remineralized tooth-lesions and neutralized acids. By combining NAg/QAM/NACP, a new class of composites and adhesives with antibacterial and remineralization double benefits was developed. Various other nanoparticles including metal and oxide nanoparticles such as ZnO and TiO2, as well as polyethylenimine nanoparticles and their antibacterial capabilities in dental resins were also reviewed. These nanoparticles are promising for incorporation into dental composites/cements/sealants/bases/liners/adhesives. Therefore, nanotechnology has potential to significantly improve restorative and preventive dentistry. PMID:25723095

  13. The use of sodium trimetaphosphate as a biomimetic analog of matrix phosphoproteins for remineralization of artificial caries-like dentin

    PubMed Central

    Liu, Yan; Li, Nan; Qi, Yipin; Niu, Li-na; Elshafiy, Sally; Mao, Jing; Breschi, Lorenzo; Pashley, David H.; Tay, Franklin R.

    2011-01-01

    Objectives This study examined the use of sodium trimetaphosphate (STMP) as a biomimetic analog of matrix phosphoproteins for remineralization of artificial carious-affected dentin. Methods Artificial carious lesions with lesion depths of 300±30 µm were created by pH-cycling. 2.5% hydrolyzed STMP was applied to the artificial carious lesions to phosphorylate the partially-demineralized collagen matrix. Half of the STMP-treated specimens were bonded with One-Step. The adhesive and non-adhesive infiltrated specimens were remineralized in a Portland cement-simulated body fluid system containing polyacrylic acid (PAA) to stabilize amorphous calcium phosphate as nanoprecursors. Micro-computed tomography (micro-CT) and transmission electron microscopy (TEM) were used to evaluate the results of remineralization after a 4-month period. Results In absence of PAA and STMP as biomimetic analogs (control groups), there was no remineralization irrespective of whether the lesions were infiltrated with adhesive. For the STMP-treated experimental groups immersed in PAA-containing simulated body fluid, specimens without adhesive infiltration were more heavily remineralized than those infiltrated with adhesive. Statistical analysis of the 4-month micro-CT data revealed significant differences in the lesion depth, relative mineral content along the lesion surface and changes in ΔZ between the non-adhesive and adhesive experimental groups (p<0.05 for all the three parameters). TEM examination indicated that collagen degradation occurred in both the non-adhesive and adhesive control and experimental groups after 4 months of remineralization. Significance Biomimetic remineralization using STMP is a promising method to remineralize artificial carious lesions particularly in areas devoid of seed crystallites. Future studies should consider the incorporation of MMP-inhibitors within the partially-demineralized collagen matrix to prevent collagen degradation during remineralization. PMID

  14. Does ozone enhance the remineralizing potential of nanohydroxyapatite on artificially demineralized enamel? A laser induced fluorescence study

    NASA Astrophysics Data System (ADS)

    Srinivasan, Samuelraj; Prabhu, Vijendra; Chandra, Subhash; Koshy, Shalini; Acharya, Shashidhar; Mahato, Krishna K.

    2014-02-01

    The present era of minimal invasive dentistry emphasizes the early detection and remineralization of initial enamel caries. Ozone has been shown to reverse the initial demineralization before the integrity of the enamel surface is lost. Nano-hydroxyapatite is a proven remineralizing agent for early enamel caries. In the present study, the effect of ozone in enhancing the remineralizing potential of nano-hydroxyapatite on artificially demineralized enamel was investigated using laser induced fluorescence. Thirty five sound human premolars were collected from healthy subjects undergoing orthodontic treatment. Fluorescence was recorded by exciting the mesial surfaces using 325 nm He-Cd laser with 2 mW power. Tooth specimens were subjected to demineralization to create initial enamel caries. Following which the specimens were divided into three groups, i.e ozone (ozonated water for 2 min), without ozone and artificial saliva. Remineralization regimen was followed for 3 weeks. The fluorescence spectra of the specimens were recorded from all the three experimental groups at baseline, after demineralization and remineralization. The average spectrum for each experimental group was used for statistical analysis. Fluorescence intensities of Ozone treated specimens following remineralization were higher than that of artificial saliva, and this difference was found to be statistically significant (P<0.0001). In a nutshell, ozone enhanced the remineralizing potential of nanohydroxyapatite, and laser induced fluorescence was found to be effective in assessing the surface mineral changes in enamel. Ozone can be considered an effective agent in reversing the initial enamel caries there by preventing the tooth from entering into the repetitive restorative cycle.

  15. Amelogenin-assisted ex vivo remineralization of human enamel: Effects of supersaturation degree and fluoride concentration.

    PubMed

    Fan, Yuwei; Nelson, James R; Alvarez, Jason R; Hagan, Joseph; Berrier, Allison; Xu, Xiaoming

    2011-05-01

    The formation of organized nanocrystals that resemble enamel is crucial for successful enamel remineralization. Calcium, phosphate and fluoride ions, and amelogenin are important ingredients for the formation of organized hydroxyapatite (HAP) crystals in vitro. However, the effects of these remineralization agents on the enamel crystal morphology have not been thoroughly studied. The objective of this study was to investigate the effects of fluoride ions, supersaturation degree and amelogenin on the crystal morphology and organization of ex vivo remineralized human enamel. Extracted third molars were sliced thin and acid-etched to provide the enamel surface for immersion in different remineralization solutions. The crystal morphology and mineral phase of the remineralized enamel surface were analyzed by field emission-scanning electron microscopy, attenuated total reflection-Fourier transformed infrared and X-ray diffraction. The concentration of fluoride and the supersaturation degree of hydroxyapatite had significant effects on the crystal morphology and crystal organization, which varied from plate-like loose crystals to rod-like densely packed nanocrystal arrays. Densely packed arrays of fluoridated hydroxyapatite nanorods were observed under the following conditions: σ(HAP)=10.2±2.0 with 1.5±0.5 mg l(-1) fluoride and 40±10 μg ml(-1) amelogenin, pH 6.8±0.4. A phase diagram summarizes the conditions that form dense or loose hydroxyapatite nanocrystal structures. This study provides the basis for the development of novel dental materials for caries management.

  16. Amelogenin-assisted ex vivo remineralization of human enamel: effects of supersaturation degree and fluoride concentration

    PubMed Central

    Fan, Yuwei; Nelson, James R.; Alvarez, Jason R.; Hagan, Joseph; Berrier, Allison; Xu, Xiaoming

    2011-01-01

    The formation of organized nanocrystals that resemble enamel is crucial for successful enamel remineralization. Calcium, phosphate and fluoride ions and amelogenin are important ingredients for the formation of organized hydroxyapatite (HAP) crystals in vitro. However, the effects of these remineralization agents on the enamel crystal morphology have not been thoroughly studied. The objective of this study was to investigate the effects of fluoride ions, supersaturation degree and amelogenin on the crystal morphology and organization of ex vivo remineralized human enamel. Extracted third molars were sliced thin and acid-etched to provide the enamel surface for immersion in different remineralization solutions. The crystal morphology and mineral phase of the remineralized enamel surface were analyzed by FE-SEM, ATR-FTIR and XRD. The concentration of fluoride and supersaturation degree of hydroxyapatite had significant effects on the crystal morphology and crystal organization, which varied from plate-like loose crystals to rod-like densely packed nanocrystal arrays. Densely packed arrays of fluoridated hydroxyapatite nanorods were observed under the following conditions: σ(HAP) = 10.2±2.0 with fluoride 1.5±0.5 mg/L and amelogenin 40±10 µg/mL, pH 6.8±0.4. A phase diagram summarized the conditions that form dense or loose hydroxyapatite nanocrystal structures. This study provides the basis for the development of novel dental materials for caries management. PMID:21256987

  17. Assessment of the remineralization in simulated enamel lesions via dehydration with near-IR reflectance imaging

    NASA Astrophysics Data System (ADS)

    Lee, Robert C.; Darling, Cynthia L.; Fried, Daniel

    2015-02-01

    Previous studies have demonstrated that near-IR imaging can be used to nondestructively monitor the severity of enamel lesions. Arrested lesions typically have a highly mineralized surface layer that reduces permeability and limits diffusion into the lesion. The purpose of this study was to investigate whether the rate of water loss correlates with the degree of remineralization using near-IR reflectance imaging. Artificial bovine (n=15) enamel lesions were prepared by immersion in a demineralization solution for 24 hours and they were subsequently placed in an acidic remineralization solution for different periods. The samples were dehydrated using an air spray for 30 seconds and surfaces were imaged using an InGaAs camera at 1300-1700 nm wavelengths. Near-IR reflectance intensity differences before and after dehydration decreased with longer periods of remineralization. This study demonstrated that near-IR reflectance imaging was suitable for the detection of remineralization in simulated caries lesions and near-IR wavelengths longer than 1400 nm are well suited for the assessment of remineralization.

  18. Reconsidering remineralization strategies to include nanoparticle hydroxyapatite.

    PubMed

    Kutsch, V Kim; Chaiyabutr, Yada; Milicich, Graeme

    2013-03-01

    Dental caries is a transmissible biofilm-mediated disease of the teeth that is defined by prolonged periods of low pH resulting in net mineral loss from the teeth. Hydroxyapatite, fluorapatite, and the carbonated forms of calcium phosphate form the main mineral content of dental hard tissues: enamel, dentin, and cementum. Active dental caries results when the biofilm pH on the tooth surface drops below the dissolution threshold for hydroxyapatite and fluorapatite. The clinical evidence of this net mineral loss is porosity, whitespot lesions, caries lesions, and/or cavitation. The potential to reverse this mineral loss through remineralization has been well documented, although previous remineralization strategies for dental hard tissues have focused on the use of fluorides and forms of calcium phosphate. This in-vitro study documented the deposition of nanoparticle hydroxyapatite on demineralized enamel surfaces after treatment with an experimental remineralization gel. This finding supports consideration of an additional approach to remineralization that includes pH neutralization strategies and nanoparticle hydroxyapatite crystals.

  19. Enamel alteration following tooth bleaching and remineralization.

    PubMed

    Coceska, Emilija; Gjorgievska, Elizabeta; Coleman, Nichola J; Gabric, Dragana; Slipper, Ian J; Stevanovic, Marija; Nicholson, John W

    2016-06-01

    The purpose of this study was to compare the effects of professional tooth whitening agents containing highly concentrated hydrogen peroxide (with and without laser activation), on the enamel surface; and the potential of four different toothpastes to remineralize any alterations. The study was performed on 50 human molars, divided in two groups: treated with Opalescence(®) Boost and Mirawhite(®) Laser Bleaching. Furthermore, each group was divided into five subgroups, a control one and 4 subgroups remineralized with: Mirasensitive(®) hap+, Mirawhite(®) Gelleѐ, GC Tooth Mousse™ and Mirafluor(®) C. The samples were analysed by SEM/3D-SEM-micrographs, SEM/EDX-qualitative analysis and SEM/EDX-semiquantitative analysis. The microphotographs show that both types of bleaching cause alterations: emphasized perikymata, erosions, loss of interprizmatic substance; the laser treatment is more aggressive and loss of integrity of the enamel is determined by shearing off the enamel rods. In all samples undergoing remineralization deposits were observed, those of toothpastes based on calcium phosphate technologies seem to merge with each other and cover almost the entire surface of the enamel. Loss of integrity and minerals were detected only in the line-scans of the sample remineralized with GC Tooth Mousse™. The semiquantitative EDX analysis of individual elements in the surface layer of the enamel indicates that during tooth-bleaching with HP statistically significant loss of Na and Mg occurs, whereas the bleaching in combination with a laser leads to statistically significant loss of Ca and P. The results undoubtedly confirm that teeth whitening procedures lead to enamel alterations. In this context, it must be noted that laser bleaching is more aggressive for dental substances. However, these changes are reversible and can be repaired by application of remineralization toothpastes.

  20. Hydroxyapatite-anchored dendrimer for in situ remineralization of human tooth enamel.

    PubMed

    Wu, Duo; Yang, Jiaojiao; Li, Jiyao; Chen, Liang; Tang, Bei; Chen, Xingyu; Wu, Wei; Li, Jianshu

    2013-07-01

    In situ remineralization of hydroxyapatite (HA) on human tooth enamel surface induced by organic matrices is of great interest in the fields of material science and stomatology. In order to mimic the organic matrices induced biomineralization process in developing enamel and enhance the binding strength at the remineralization interface, carboxyl-terminated poly(amido amine) (PAMAM-COOH)-alendronate (ALN) conjugate (ALN-PAMAM-COOH) was synthesized and characterized. PAMAM-COOH has a highly ordered architecture and is capable of promoting the HA crystallization process. ALN is conjugated on PAMAM-COOH due to its specific adsorption on HA (the main component of tooth enamel), resulting in increased binding strength which is tight enough to resist phosphate buffered saline (PBS) rinsing as compared with that of PAMAM-COOH alone. While incubated in artificial saliva, ALN-PAMAM-COOH could induce in situ remineralization of HA on acid-etched enamel, and the regenerated HA has the nanorod-like crystal structure similar to that of human tooth enamel. The hardness of acid-etched enamel samples treated by ALN-PAMAM-COOH can recover up to 95.5% of the original value with strong adhesion force. In vivo experiment also demonstrates that ALN-PAMAM-COOH is effective in repairing acid-etched enamel in the oral cavity. Overall, these results suggest that ALN-PAMAM-COOH is highly promising as a restorative biomaterial for in situ remineralization of human tooth enamel.

  1. Influence of remineralizing gels on bleached enamel microhardness in different time intervals.

    PubMed

    Borges, Alessandra Bühler; Yui, Karen Cristina Kazue; D'Avila, Thaís Corrêa; Takahashi, Camila Lurie; Torres, Carlos Rocha Gomes; Borges, Alexandre Luis Souto

    2010-01-01

    This study evaluated the influence of bleaching gel pH, the effect of applying remineralizing gels after bleaching and the effect of artificial saliva on enamel microhardness. Seventy bovine incisors were divided into three groups: Group 1 (n=10) received no bleaching procedure (control); Group 2 was bleached with a 35% hydrogen peroxide neutral gel (n=30) and Group 3 was bleached with a 35% hydrogen peroxide acid gel (n=30). Each experimental group was subdivided into three groups (n=10) according to the post-bleaching treatment: storage in artificial saliva, application of a fluoride gel and application of a combination of calcium and fluoride gel. The specimens were stored in artificial saliva for 7, 15 and 30 days and enamel microhardness was evaluated. The Vickers microhardness data were analyzed by three-way RM ANOVA, which revealed a significant difference only for treatment factor. The Tukey's test showed that the groups bleached followed by no additional treatment exhibited microhardness means significantly lower than the bleached groups treated with remineralizing gels. The Dunnet's test showed a significant difference only for the group bleached with acid gel without remineralizing treatment compared to the control group measured immediately after bleaching. It was concluded that acid bleaching gel significantly reduced enamel microhardness and that use of remineralizing gels after bleaching can significantly enhance the microhardness of bleached enamel.

  2. Tranexamic acid mouthwash--a prospective randomized study of a 2-day regimen vs 5-day regimen to prevent postoperative bleeding in anticoagulated patients requiring dental extractions.

    PubMed

    Carter, G; Goss, A

    2003-10-01

    This prospective randomized study analyses the use of a prescribed 4.8% tranexamic acid post-operative mouthwash over 2 days vs 5 days to prevent bleeding in patients taking warfarin who require dental extractions. Eighty-five patients therapeutically anticoagulated with warfarin for various conditions, ranging in age from 21 to 86 years and requiring dental extractions, were randomly divided into two groups. Group A postoperatively received a 4.8% tranexamic acid mouthwash to be used over a 2-day period. Group B received the same mouthwash and instructions postoperatively, to be taken over 5 days. All procedures were performed on an ambulatory basis under local anaesthetic by the same surgeon. Patients were reviewed 1, 3, and 7 days postoperatively to assess bleeding. Eighty-two of the 85 patients encountered no postoperative problems. Two patients in group A and one in group B had minor postoperative bleeds that required minor ambulatory intervention to control. This study shows that a 2-day postoperative course of a 4.8% tranexamic acid mouthwash is as equally effective as a 5-day course in controlling haemostasis post-dental extractions in patient's anticoagulated with warfarin.

  3. Quantitative examination of demineralized and remineralized dental lesions using photothermal radiometry and modulated luminescence

    NASA Astrophysics Data System (ADS)

    Hellen, Adam; Mandelis, Andreas; Finer, Yoav; Amaechi, Bennett

    2010-02-01

    The development of photothermal techniques to detect thermal waves in biological tissue has occurred with a concomitant advancement in the extraction of material thermophysical properties and knowledge regarding the internal structure of a medium. Human molars (n=37) were subjected to demineralization in acid gel (pH 4.5, 10 days), followed by incubation in different fluoride-containing remineralization solutions. PTR-LUM frequency scans (1 Hz - 1 kHz) were performed prior to and during demineralization and remineralization treatments. Transverse Micro-Radiography (TMR) analysis followed at treatment conclusion. A coupled diffuse-photon-density-wave and thermal-wave theoretical model was used to quantitatively evaluate changes in thermal and optical properties of sound, demineralized and remineralized enamel. Amplitude increase and phase lag decrease in demineralized samples were consistent with higher scatter of the diffuse-photon density field and thermal wave confinement to near-surface regions. A remineralized sample illustrates a complex interplay between surface and subsurface processes, confining the thermal-wave centroid toward the dominating layer. PTR-LUM sensitivity to changes in tooth mineralization coupled with optical and thermal property extraction illustrates the technique's potential for non-destructive evaluation of multi-layered turbid media.

  4. A Chemical Phosphorylation-inspired Design for Type I Collagen Biomimetic Remineralization

    PubMed Central

    Gu, Li-sha; Kim, Jongryul; Kim, Young Kyung; Liu, Yan; Dickens, Sabine H.; Pashley, David H.; Ling, Jun-qi; Tay, Franklin R.

    2010-01-01

    Objectives Type I collagen alone cannot initiate tissue mineralization. Sodium trimetaphosphate (STMP) is frequently employed as a chemical phosphorylating reagent in the food industry. This study examined the feasibility of using STMP as a functional analog of matrix phosphoproteins for biomimetic remineralization of resin-bonded dentin. Methods Equilibrium adsorption and desorption studies of STMP were performed using demineralized dentin powder (DDP). Interaction between STMP and DDP was examined using Fourier-transform infrared spectroscopy. Based on those results, a bio-inspired mineralization scheme was developed for chemical phosphorylation of acid-etched dentin with STMP, followed by infiltration of the STMP-treated collagen matrix with two etch-and-rinse adhesives. Resin-dentin interfaces were remineralized in a Portland cement-simulated body fluid system, with or without the use of polyacrylic acid (PAA) as a dual biomimetic analog. Remineralized resin-dentin interfaces were examined unstained using transmission electron microscopy. Results Analysis of saturation binding curves revealed the presence of irreversible phosphate group binding sites on the surface of the DDP. FT-IR provided additional evidence of chemical interaction between STMP and DDP, with increased in the peak intensities of the P=O and P–O–C stretching modes. Those peaks returned to their original intensities after alkaline phosphatase treatment. Evidence of intrafibrillar apatite formation could be seen in incompletely resin-infiltrated, STMP-phosphorylated collagen matrices only when PAA was present in the SBF. Significance These results reinforce the importance of PAA for sequestration of amorphous calcium phosphate nanoprecursors in the biomimetic remineralization scheme. They also highlight the role of STMP as a templating analog of dentin matrix phosphoproteins for inducing intrafibrillar remineralization of apatite nanocrystals within the collagen matrix of incompletely resin

  5. Effect of Green and White Tea Pretreatment on Remineralization of Demineralized Dentin by CPP-ACFP-An Invitro Microhardness Analysis

    PubMed Central

    Jose, Poornima; Sekar, Mahalaxmi

    2016-01-01

    Introduction Mechanical performance of dentine is of major significance for the overall function of the teeth. Remineralization of carious dentine is the ultimate goal in re-establishing the functionality of the affected tissue so as to regain and maintain the mechanical properties of dentine. Functional remineralization of the affected dentin involves stabilization of both inorganic and organic component, but Caesin Phosphopeptide Amorphous Calcium Flurophosphate (CPP-ACFP) stabilizes only inorganic content. Hence to stabilize organic content and to bring in functional remineralization the use of anticollagenolytic and antielastastic agent was considered for this study. Aim To assess and compare the remineralization of artificial carious dentin pre treated with white and green tea, before and after application of CPP-ACFP using microhardness test. Null hypothesis was that both teas did not have any effect on remineralization potential of CPP ACFP. Materials and Methods Forty specimens were subjected to artificial caries lesions and were randomly divided into 4 groups based on the application of tea extract followed by CPP-ACFP (groups A & B) and CPP-ACFP followed by tea extracts (groups C & D). All the specimens were subjected to two pH cycling regimen. The specimens were subjected to Vickers microhardness test to obtain the microhardness values. The values were statistically analysed using one-way ANOVA and multiple comparisons with Tukey’s HSD procedure. Results After the 1st and 2nd pH cycling in groups A and B, Group B showed significant increase in microhardness values (35.79± 3.12 VHN). But after the pH cycling regimen in groups C and D, microhardness values increased in 1st pH cycling (50.03± 3.64 VHN); (50.03±3.64 VHN), respectively but decreased during the 2nd pH cycling, (33.94±6.45 VHN); (33.11±6.11 VHN) respectively with the level of significance <0.05. Conclusion The results of this study rejects the hypothesis tested and showed that both the

  6. Functional biomimetic analogs help remineralize apatite-depleted demineralized resin-infiltrated dentin via a bottom-up approach.

    PubMed

    Kim, Jongryul; Arola, Dwayne D; Gu, Lisha; Kim, Young Kyung; Mai, Sui; Liu, Yan; Pashley, David H; Tay, Franklin R

    2010-07-01

    Natural biominerals are formed through metastable amorphous precursor phases via a bottom-up, nanoparticle-mediated mineralization mechanism. Using an acid-etched human dentin model to create a layer of completely demineralized collagen matrix, a bio-inspired mineralization scheme has been developed based on the use of dual biomimetic analogs. These analogs help to sequester fluidic amorphous calcium phosphate nanoprecursors and function as templates for guiding homogeneous apatite nucleation within the collagen fibrils. By adopting this scheme for remineralizing adhesive resin-bonded, completely demineralized dentin, we have been able to redeposit intrafibrillar and extrafibrillar apatites in completely demineralized collagen matrices that are imperfectly infiltrated by resins. This study utilizes a spectrum of completely and partially demineralized dentin collagen matrices to further validate the necessity for using a biomimetic analog-containing medium for remineralizing resin-infiltrated partially demineralized collagen matrices in which remnant seed crystallites are present. In control specimens in which biomimetic analogs are absent from the remineralization medium, remineralization could only be seen in partially demineralized collagen matrices, probably by epitaxial growth via a top-down crystallization approach. Conversely, in the presence of biomimetic analogs in the remineralization medium, intrafibrillar remineralization of completely demineralized collagen matrices via a bottom-up crystallization mechanism can additionally be identified. The latter is characterized by the transition of intrafibrillar minerals from an inchoate state of continuously braided microfibrillar electron-dense amorphous strands to discrete nanocrystals, and ultimately into larger crystalline platelets within the collagen fibrils. Biomimetic remineralization via dual biomimetic analogs has the potential to be translated into a functional delivery system for salvaging failing

  7. Effects of Treatment with Various Remineralizing Agents on the Microhardness of Demineralized Enamel Surface.

    PubMed

    Salehzadeh Esfahani, Kiana; Mazaheri, Romina; Pishevar, Leila

    2015-01-01

    Background and aims. Remineralization of incipient caries is one of the goals in dental health care. The present study aimed at comparing the effects of casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP), Remin Pro(®), and 5% sodium fluoride varnish on remineralization of enamel lesions. Materials and methods. In this in vitro study, 60 enamel samples were randomly allocated to six groups of 10. After four days of immersion in demineralizing solution, microhardness of all samples was measured. Afterward, groups 1-3 underwent one-time treatment with fluoride varnish, CPP-ACP, and Remin Pro(®), respectively. Microhardness of groups 4-6 was measured not only after one-month treatment with the above-mentioned materials (for eight hours a day), but also after re-exposing to the demineralizing solution. The results were analyzed by one-way analysis of variance (ANOVA), repeated measures ANOVA, and Fisher's least significant difference (LSD) test. Results . None of the regimens could increase microhardness in groups 1-3. However, one-month treatment regimens in groups 4-6 caused a significant increase in microhardness. The greatest microhardness was detected in the group treated with CPP-ACP (P = 0.001). In addition, although microhardness reduced following re-demineralization in all three groups, the mean reduction was minimum in the CPP-ACP-treated group (P < 0.001). Conclusion. While long-term repeated application of all compounds improved microhardness, the remineralization potential of CPP-ACP was significantly higher than that of Remin Pro(®) and sodium fluoride varnish.

  8. Effects of Treatment with Various Remineralizing Agents on the Microhardness of Demineralized Enamel Surface

    PubMed Central

    Salehzadeh Esfahani, Kiana; Mazaheri, Romina; Pishevar, Leila

    2015-01-01

    Background and aims. Remineralization of incipient caries is one of the goals in dental health care. The present study aimed at comparing the effects of casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP), Remin Pro®, and 5% sodium fluoride varnish on remineralization of enamel lesions. Materials and methods. In this in vitro study, 60 enamel samples were randomly allocated to six groups of 10. After four days of immersion in demineralizing solution, microhardness of all samples was measured. Afterward, groups 1-3 underwent one-time treatment with fluoride varnish, CPP-ACP, and Remin Pro®, respectively. Microhardness of groups 4-6 was measured not only after one-month treatment with the above-mentioned materials (for eight hours a day), but also after re-exposing to the demineralizing solution. The results were analyzed by one-way analysis of variance (ANOVA), repeated measures ANOVA, and Fisher’s least significant difference (LSD) test. Results. None of the regimens could increase microhardness in groups 1-3. However, one-month treatment regimens in groups 4-6 caused a significant increase in microhardness. The greatest microhardness was detected in the group treated with CPP-ACP (P = 0.001). In addition, although microhardness reduced following re-demineralization in all three groups, the mean reduction was minimum in the CPP-ACP-treated group (P < 0.001). Conclusion. While long-term repeated application of all compounds improved microhardness, the remineralization potential of CPP-ACP was significantly higher than that of Remin Pro® and sodium fluoride varnish. PMID:26889361

  9. Photothermal radiometry and modulated luminescence examination of demineralized and remineralized dental lesions

    NASA Astrophysics Data System (ADS)

    Hellen, A.; Mandelis, A.; Finer, Y.

    2010-03-01

    Dental caries involves continuous challenges of acid-induced mineral loss and a counteracting process of mineral recovery. As an emerging non-destructive methodology, photothermal radiometry and modulated luminescence (PTR-LUM) has shown promise in measuring changes in tooth mineral content. Human molars (n=37) were subjected to demineralization in acid gel (pH 4.5, 10 days), followed by incubation in remineralisation solutions (pH 6.7, 4 weeks) without or with fluoride (1 or 1000 ppm). PTR-LUM frequency scans (1 Hz - 1 kHz) were performed prior to and during demineralization and remineralization treatments. Transverse Micro-Radiography (TMR) analysis followed at treatment conclusion. The non-fluoridated group exhibited opposite amplitude and phase trends to those of the highly fluoridated group: smaller phase lag and larger amplitude. These results point to a complex interplay between surface and subsurface processes during remineralization, confining the thermal-wave centroid toward the dominating layer.

  10. Oriented and Ordered Biomimetic Remineralization of the Surface of Demineralized Dental Enamel Using HAP@ACP Nanoparticles Guided by Glycine.

    PubMed

    Wang, Haorong; Xiao, Zuohui; Yang, Jie; Lu, Danyang; Kishen, Anil; Li, Yanqiu; Chen, Zhen; Que, Kehua; Zhang, Qian; Deng, Xuliang; Yang, Xiaoping; Cai, Qing; Chen, Ning; Cong, Changhong; Guan, Binbin; Li, Ting; Zhang, Xu

    2017-01-12

    Achieving oriented and ordered remineralization on the surface of demineralized dental enamel, thereby restoring the satisfactory mechanical properties approaching those of sound enamel, is still a challenge for dentists. To mimic the natural biomineralization approach for enamel remineralization, the biological process of enamel development proteins, such as amelogenin, was simulated in this study. In this work, carboxymethyl chitosan (CMC) conjugated with alendronate (ALN) was applied to stabilize amorphous calcium phosphate (ACP) to form CMC/ACP nanoparticles. Sodium hypochlorite (NaClO) functioned as the protease which decompose amelogenin in vivo to degrade the CMC-ALN matrix and generate HAP@ACP core-shell nanoparticles. Finally, when guided by 10 mM glycine (Gly), HAP@ACP nanoparticles can arrange orderly and subsequently transform from an amorphous phase to well-ordered rod-like apatite crystals to achieve oriented and ordered biomimetic remineralization on acid-etched enamel surfaces. This biomimetic remineralization process is achieved through the oriented attachment (OA) of nanoparticles based on non-classical crystallization theory. These results indicate that finding and developing analogues of natural proteins such as amelogenin involved in the biomineralization by natural macromolecular polymers and imitating the process of biomineralization would be an effective strategy for enamel remineralization. Furthermore, this method represents a promising method for the management of early caries in minimal invasive dentistry (MID).

  11. Oriented and Ordered Biomimetic Remineralization of the Surface of Demineralized Dental Enamel Using HAP@ACP Nanoparticles Guided by Glycine

    NASA Astrophysics Data System (ADS)

    Wang, Haorong; Xiao, Zuohui; Yang, Jie; Lu, Danyang; Kishen, Anil; Li, Yanqiu; Chen, Zhen; Que, Kehua; Zhang, Qian; Deng, Xuliang; Yang, Xiaoping; Cai, Qing; Chen, Ning; Cong, Changhong; Guan, Binbin; Li, Ting; Zhang, Xu

    2017-01-01

    Achieving oriented and ordered remineralization on the surface of demineralized dental enamel, thereby restoring the satisfactory mechanical properties approaching those of sound enamel, is still a challenge for dentists. To mimic the natural biomineralization approach for enamel remineralization, the biological process of enamel development proteins, such as amelogenin, was simulated in this study. In this work, carboxymethyl chitosan (CMC) conjugated with alendronate (ALN) was applied to stabilize amorphous calcium phosphate (ACP) to form CMC/ACP nanoparticles. Sodium hypochlorite (NaClO) functioned as the protease which decompose amelogenin in vivo to degrade the CMC-ALN matrix and generate HAP@ACP core-shell nanoparticles. Finally, when guided by 10 mM glycine (Gly), HAP@ACP nanoparticles can arrange orderly and subsequently transform from an amorphous phase to well-ordered rod-like apatite crystals to achieve oriented and ordered biomimetic remineralization on acid-etched enamel surfaces. This biomimetic remineralization process is achieved through the oriented attachment (OA) of nanoparticles based on non-classical crystallization theory. These results indicate that finding and developing analogues of natural proteins such as amelogenin involved in the biomineralization by natural macromolecular polymers and imitating the process of biomineralization would be an effective strategy for enamel remineralization. Furthermore, this method represents a promising method for the management of early caries in minimal invasive dentistry (MID).

  12. Oriented and Ordered Biomimetic Remineralization of the Surface of Demineralized Dental Enamel Using HAP@ACP Nanoparticles Guided by Glycine

    PubMed Central

    Wang, Haorong; Xiao, Zuohui; Yang, Jie; Lu, Danyang; Kishen, Anil; Li, Yanqiu; Chen, Zhen; Que, Kehua; Zhang, Qian; Deng, Xuliang; Yang, Xiaoping; Cai, Qing; Chen, Ning; Cong, Changhong; Guan, Binbin; Li, Ting; Zhang, Xu

    2017-01-01

    Achieving oriented and ordered remineralization on the surface of demineralized dental enamel, thereby restoring the satisfactory mechanical properties approaching those of sound enamel, is still a challenge for dentists. To mimic the natural biomineralization approach for enamel remineralization, the biological process of enamel development proteins, such as amelogenin, was simulated in this study. In this work, carboxymethyl chitosan (CMC) conjugated with alendronate (ALN) was applied to stabilize amorphous calcium phosphate (ACP) to form CMC/ACP nanoparticles. Sodium hypochlorite (NaClO) functioned as the protease which decompose amelogenin in vivo to degrade the CMC-ALN matrix and generate HAP@ACP core-shell nanoparticles. Finally, when guided by 10 mM glycine (Gly), HAP@ACP nanoparticles can arrange orderly and subsequently transform from an amorphous phase to well-ordered rod-like apatite crystals to achieve oriented and ordered biomimetic remineralization on acid-etched enamel surfaces. This biomimetic remineralization process is achieved through the oriented attachment (OA) of nanoparticles based on non-classical crystallization theory. These results indicate that finding and developing analogues of natural proteins such as amelogenin involved in the biomineralization by natural macromolecular polymers and imitating the process of biomineralization would be an effective strategy for enamel remineralization. Furthermore, this method represents a promising method for the management of early caries in minimal invasive dentistry (MID). PMID:28079165

  13. Effect of Lesion Baseline Severity and Mineral Distribution on Remineralization and Progression of Human and Bovine Dentin Caries Lesions.

    PubMed

    Lippert, Frank; Churchley, David; Lynch, Richard J

    2015-01-01

    The aims of this laboratory study were to compare the effects of lesion baseline severity, mineral distribution and substrate on remineralization and progression of caries lesions created in root dentin. Lesions were formed in dentin specimens prepared from human and bovine dentin using three protocols, each utilizing three demineralization periods to create lesions of different mineral distributions (subsurface, moderate softening, extreme softening) and severity within each lesion type. Lesions were then either remineralized or demineralized further and analyzed using transverse microradiography. At lesion baseline, no differences were found between human and bovine dentin for integrated mineral loss (x0394;Z). Differences in mineral distribution between lesion types were apparent. Human dentin lesions were more prone to secondary demineralization (x0394;x0394;Z) than bovine dentin lesions, although there were no differences in x0394;L. Likewise, smaller lesions were more susceptible to secondary demineralization than larger ones. Subsurface lesions were more acid-resistant than moderately and extremely softened lesions. After remineralization, differences between human and bovine dentin lesions were not apparent for x0394;x0394;Z although bovine dentin lesions showed greater reduction in lesion depth L. For lesion types, responsiveness to remineralization (x0394;x0394;Z) was in the order extremely softened>moderately softened>subsurface. More demineralized lesions exhibited greater remineralization than shallower ones. In summary, some differences exist between human and bovine dentin and their relative responsiveness to de- and remineralization. These differences, however, were overshadowed by the effects of lesion baseline mineral distribution and severity. Thus, bovine dentin appears to be a suitable substitute for human dentin in mechanistic root caries studies.

  14. Imaging analysis of early DMP1 mediated dentin remineralization

    PubMed Central

    Bedran-Russo, Ana K.; Ravindran, Sriram; George, Anne

    2013-01-01

    Objective This study assessed the micro-morphological changes in demineralized dentin scaffold following incubation with recombinant dentin matrix protein 1 (rDMP1). Design Extracted human molar crowns were sectioned into 6 beams (dimensions: 0.50 × 1.70 × 6.0 mm), demineralized and incubated overnight in 3 different media (n = 4): rDMP1 in bovine serum albumin (BSA), BSA and distilled water. Samples were placed in a chamber with simulated physiological concentrations of calcium and phosphate ions at constant pH 7.4. Samples were immediately processed for transmission electron microscopy (TEM) and field emission-scanning electron microscopy (FE-SEM) after 1 and 2 weeks. Results Analysis of the scaffold showed that decalcification process retained the majority of endogenous proteoglycans and phosphoproteins. rDMP1 treated samples promoted deposition of amorphous calcium phosphate (ACP) precursors and needle shaped hydroxyapatite crystals surrounding collagen fibrils. The BSA group presented ACP bound to collagen with no needle-like apatite crystals. Samples kept in distilled water showed no evidence of ACP and crystal apatite. Results from rDMP1 immobilized on dentin matrix suggests that the acidic protein was able to bind to collagen fibrils and control formation of amorphous calcium phosphate and its subsequent transformation into hydroxyapatite crystals after 2 weeks. Conclusion These findings suggest a possible bio-inspired strategy to promote remineralization of dentin for reparative and regenerative purposes. PMID:23107046

  15. A comparative evaluation of remineralizing ability of bioactive glass and amorphous calcium phosphate casein phosphopeptide on early enamel lesion

    PubMed Central

    Palaniswamy, Udaya Kumar; Prashar, Neha; Kaushik, Mamta; Lakkam, Surender Ram; Arya, Shikha; Pebbeti, Swetha

    2016-01-01

    Background: This study was done to evaluate remineralizing potential of bioactive glasses (BAGs) and amorphous calcium phosphate-casein phosphopeptide (ACP-CPP) on early enamel lesion. Materials and Methods: Twenty freshly extracted mandibular premolars were sectioned sagittally. The buccal half was impregnated in acrylic resin blocks and treated with 37% phosphoric acid in liquid form, to demineralize enamel surface to simulate early enamel lesion. The samples were divided into two groups. The samples in Group I were treated with ACP-CPP (GC Tooth Mousse) and in Group II with BAG (Sensodyne Repair and Protect) and stored in saliva to prevent dehydration. The samples were tested for microhardness. The data obtained was analyzed using ANOVA post hoc multiple comparison and independent sample t- test and presented as a mean and standard deviation. Results: All the samples showed a decrease in the microhardness after demineralization. After application of remineralizing agents, Group II showed a highly significant increase in the microhardness (P < 0.05) after 10 days, while Group I showed a significant increase in microhardness after 15 days (P < 0.05). Conclusion: Both the remineralizing agents tested in this study can be considered effective in repair and prevention of demineralization. BAG showed better results initially, but eventually both have similar remineralizing potential. PMID:27605985

  16. Clinical significance of CD56 expression in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens.

    PubMed

    Montesinos, Pau; Rayón, Chelo; Vellenga, Edo; Brunet, Salut; González, José; González, Marcos; Holowiecka, Aleksandra; Esteve, Jordi; Bergua, Juan; González, José D; Rivas, Concha; Tormo, Mar; Rubio, Vicente; Bueno, Javier; Manso, Félix; Milone, Gustavo; de la Serna, Javier; Pérez, Inmaculada; Pérez-Encinas, Manuel; Krsnik, Isabel; Ribera, Josep M; Escoda, Lourdes; Lowenberg, Bob; Sanz, Miguel A

    2011-02-10

    The expression of CD56 antigen in acute promyelocytic leukemia (APL) blasts has been associated with short remission duration and extramedullary relapse. We investigated the clinical significance of CD56 expression in a large series of patients with APL treated with all-trans retinoic acid and anthracycline-based regimens. Between 1996 and 2009, 651 APL patients with available data on CD56 expression were included in 3 subsequent trials (PETHEMA LPA96 and LPA99 and PETHEMA/HOVON LPA2005). Seventy-two patients (11%) were CD56(+) (expression of CD56 in ≥ 20% leukemic promyelocytes). CD56(+) APL was significantly associated with high white blood cell counts; low albumin levels; BCR3 isoform; and the coexpression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. For CD56(+) APL, the 5-year relapse rate was 22%, compared with a 10% relapse rate for CD56(-) APL (P = .006). In the multivariate analysis, CD56 expression retained the statistical significance together with the relapse-risk score. CD56(+) APL also showed a greater risk of extramedullary relapse (P < .001). In summary, CD56 expression is associated with the coexpression of immaturity-associated and T-cell antigens and is an independent adverse prognostic factor for relapse in patients with APL treated with all-trans-retinoic acid plus idarubicin-derived regimens. This marker may be considered for implementing risk-adapted therapeutic strategies in APL. The LPA2005 trial is registered at http://www.clinicaltrials.gov as NCT00408278.

  17. Elevated fluoride products enhance remineralization of advanced enamel lesions.

    PubMed

    ten Cate, J M; Buijs, M J; Miller, C Chaussain; Exterkate, R A M

    2008-10-01

    Caries prevention might benefit from the use of toothpastes containing over 1500 ppm F. With few clinical studies available, the aim of this pH-cycling study was to investigate the dose response between 0 and 5000 ppm F of de- and remineralization of advanced (> 150 microm) enamel lesions. Treatments included sodium and amine fluoride, and a fluoride-free control. Mineral uptake and loss were assessed from solution calcium changes and microradiographs. Treatments with 5000 ppm F both significantly enhanced remineralization and inhibited demineralization when compared with treatments with 1500 ppm F. Slight differences in favor of amine fluoride over sodium fluoride were observed. The ratio of de- over remineralization rates decreased from 13.8 to 2.1 in the range 0 to 5000 ppm F. As much as 71 (6)% of the remineralized mineral was calculated to be resistant to dissolution during subsequent demineralization periods. With 5000-ppm-F treatments, more demineralizing episodes per day (10 vs. 2 for placebo) would still be repaired by remineralization.

  18. Comparative Evaluation of Remineralizing Potential of Three Pediatric Dentifrices

    PubMed Central

    Kapoor, Ashna; Indushekar, KR; Saraf, Bhavna G; Sheoran, Neha

    2016-01-01

    Introduction Dentifrices are available in different formulations and more commonly a single dentifrice is used by whole family; be it an adult or child. However, concerns over high fluoride in pediatric formulations coupled with inability of the children to spit have led to recommendations to minimize fluoride ingestion during toothbrushing by using a small amount of toothpaste by children and incorporating minimal quantity of fluoride in the toothpastes. Literature is scarce on the remineralization potential of popularly known Indian pediatric dentifrices; hence, pediatric dentifrices containing lesser concentration of fluoride have been marketed relatively recently for the benefit of children without posing a threat of chronic fluoride toxicity at the same time. Aim and objectives The present study was undertaken to evaluate and compare the remineralization potential of three commercially available Indian pediatric dentifrices with different compositions on artificially induced carious lesions in vitro through scanning electron microscopy (SEM). Materials and methods The present in vitro study was conducted on 45 sound extracted primary molar surfaces divided into three groups (15 each). Artificial demineralization was carried out, followed by remineralization using dentifrice slurry as per the group allocation. All the samples were studied for remineralization using SEM and the results statistically compared. Results All three dentifrices tested showed remineralization; although insignificantly different from each other but significantly higher compared to the demineralizing surface. Conclusion One can use pediatric dentifrices for preventing dental caries and decelerating lesion progression with an added advantage of lower fluoride toxicity risk. How to cite this article Kapoor A, Indushekar KR, Saraf BG, Sheoran N, Sardana D. Comparative Evaluation of Remineralizing Potential of Three Pediatric Dentifrices. Int J Clin Pediatr Dent 2016;9(3):186-191. PMID

  19. Evaluation of antibacterial and remineralizing nanocomposite and adhesive in rat tooth cavity model

    PubMed Central

    Li, Fang; Wang, Ping; Weir, Michael D.; Fouad, Ashraf F.; Xu, Hockin H. K.

    2014-01-01

    Antibacterial and remineralizing dental composites and adhesives were recently developed to inhibit biofilm acids and combat secondary caries. It is not clear what effect these materials will have on dental pulps in vivo. The objectives of this study were to investigate the antibacterial and remineralizing restorations in a rat tooth cavity model, and determine pulpal inflammatory response and tertiary dentin formation. Nanoparticles of amorphous calcium phosphate (NACP) and antibacterial dimethylaminododecyl methacrylate (DMADDM) were synthesized and incorporated into a composite and an adhesive. Occlusal cavities were prepared in the first molars of rats and restored with four types of restoration: Control composite and adhesive; control plus DMADDM; control plus NACP; and control plus both DMADDM and NACP. At 8 or 30 days (d), rat molars were harvested for histological analysis. For inflammatory cell response, regardless of time periods, NACP group and DMADDM+NACP group showed lower scores (better biocompatibility) than control group (p = 0.014 for 8 d, p = 0.018 for 30 d). For tissue disorganization, NACP and DMADDM+NACP had better scores than control (p = 0.027) at 30 d. At 8 d, restorations containing NACP had tertiary dentin thickness (TDT) that was 5-6 fold that of control. At 30 d, restorations containing NACP had TDT that was 4-6 fold that of control. In conclusion, novel antibacterial and remineralizing restorations were tested in rat teeth in vivo for the first time. Composite and adhesive containing NACP and DMADDM exhibited milder pulpal inflammation and much greater tertiary dentin formation, than control adhesive and composite. Therefore, the novel composite and adhesive containing NACP and DMADDM are promising as a new therapeutic restorative system to not only combat oral pathogens and biofilm acids as shown previously, but also facilitate the healing of the dentin-pulp complex. PMID:24583320

  20. Near-surface structural examination of human tooth enamel subject to in vitro demineralization and remineralization

    NASA Astrophysics Data System (ADS)

    Gaines, Carmen Veronica

    The early stages of chemical tooth decay are governed by dynamic processes of demineralization and remineralization of dental enamel that initiates along the surface of the tooth. Conventional diagnostic techniques lack the spatial resolution required to analyze near-surface structural changes in enamel at the submicron level. In this study, slabs of highly-polished, decay-free human enamel were subjected to 0.12M EDTA and buffered lactic acid demineralizing agents and MI Paste(TM) and calcifying (0.1 ppm F) remineralizing treatments in vitro. Grazing incidence x-ray diffraction (GIXD), a technique typically used for thin film analysis, provided depth profiles of crystallinity changes in surface enamel with a resolution better than 100 nm. In conjunction with nanoindentation, a technique gaining acceptance as a means of examining the mechanical properties of sound enamel, these results were corroborated with well-established microscopy and Raman techniques to assess the nanohardness, morphologies and chemical nature of treated enamel. Interestingly, the average crystallite size of surface enamel along its c-axis dimension increased by nearly 40% after a 60 min EDTA treatment as detected by GIXD. This result was in direct contrast to the obvious surface degradation observed by microscopic and confocal Raman imaging. A decrease in nanohardness from 4.86 +/- 0.44 GPa to 0.28 +/- 0.10 GPa was observed. Collective results suggest that mineral dissolution characteristics evident on the micron scale may not be fully translated to the nanoscale in assessing the integrity of chemically-modified tooth enamel. While an intuitive decrease in enamel crystallinity was observed with buffered lactic acid-treated samples, demineralization was too slow to adequately quantify the enamel property changes seen. MI Paste(TM) treatment of EDTA-demineralized enamel showed preferential growth along the a-axis direction. Calcifying solution treatments of both demineralized sample types

  1. In vitro remineralization of hybrid layers using biomimetic analogs*

    PubMed Central

    Lin, Hui-ping; Lin, Jun; Li, Juan; Xu, Jing-hong; Mehl, Christian

    2016-01-01

    Resin-dentin bond degradation is a major cause of restoration failures. The major aim of the current study was to evaluate the impact of a remineralization medium on collagen matrices of hybrid layers of three different adhesive resins using nanotechnology methods. Coronal dentin surfaces were prepared from freshly extracted premolars and bonded to composite resin using three adhesive resins (FluoroBond II, Xeno-III-Bond, and iBond). From each tooth, two central slabs were selected for the study. The slabs used as controls were immersed in a simulated body fluid (SBF). The experimental slabs were immersed in a Portland cement-based remineralization medium that contained two biomimetic analogs (biomineralization medium (BRM)). Eight slabs per group were retrieved after 1, 2, 3, and 4 months, respectively and immersed in Rhodamine B for 24 h. Confocal laser scanning microscopy was used to evaluate the permeability of hybrid layers to Rhodamine B. Data were analyzed by analysis of variance (ANOVA) and Tukey’s honest significant difference (HSD) tests. After four months, all BRM specimens exhibited a significantly smaller fluorescent area than SBF specimens, indicating a remineralization of the hybrid layer (P≤0.05). A clinically applicable biomimetic remineralization delivery system could potentially slow down bond degradation. PMID:27819133

  2. Effect of in vitro chewing and bruxism events on remineralization, at the resin-dentin interface.

    PubMed

    Toledano, Manuel; Cabello, Inmaculada; Aguilera, Fátima S; Osorio, Estrella; Osorio, Raquel

    2015-01-02

    The purpose of this study was to evaluate if different in vitro functional and parafunctional habits promote mineralization at the resin-dentin interface after bonding with three different adhesive approaches. Dentin surfaces were subjected to distinct treatments: demineralization by (1) 37% phosphoric acid (PA) followed by application of an etch-and-rinse dentin adhesive, Single Bond (SB) (PA+SB); (2) 0.5 M ethylenediaminetetraacetic acid (EDTA) followed by SB (EDTA+SB); (3) application of a self-etch dentin adhesive, Clearfil SE Bond (SEB). Different loading waveforms were applied: No cycling (I), cycled in sine (II) or square (III) waves, sustained loading hold for 24 h (IV) or sustained loading hold for 72 h (V). Remineralization at the bonded interfaces was assessed by AFM imaging/nano-indentation, Raman spectroscopy and Masson's trichrome staining. In general, in vitro chewing and parafunctional habits, promoted an increase of nano-mechanical properties at the resin-dentin interface. Raman spectroscopy through cluster analysis demonstrated an augmentation of the mineral-matrix ratio in loaded specimens. Trichrome staining reflected a narrow demineralized dentin matrix after loading in all groups except in PA+SB and EDTA+SB samples after sustained loading hold for 72 h, which exhibited a strong degree of mineralization. In vitro mechanical loading, produced during chewing and bruxism (square or hold 24 and 72 h waveforms), induced remineralization at the resin-dentin bonded interface.

  3. A Post-stroke Therapeutic Regimen with Omega-3 Polyunsaturated Fatty Acids that Promotes White Matter Integrity and Beneficial Microglial Responses after Cerebral Ischemia.

    PubMed

    Jiang, Xiaoyan; Pu, Hongjian; Hu, Xiaoming; Wei, Zhishuo; Hong, Dandan; Zhang, Wenting; Gao, Yanqin; Chen, Jun; Shi, Yejie

    2016-12-01

    White matter injury induced by ischemic stroke elicits sensorimotor impairments, which can be further deteriorated by persistent proinflammatory responses. We previously reported that delayed and repeated treatments with omega-3 polyunsaturated fatty acids (n-3 PUFAs) improve spatial cognitive functions and hippocampal integrity after ischemic stroke. In the present study, we report a post-stroke n-3 PUFA therapeutic regimen that not only confers protection against neuronal loss in the gray matter but also promotes white matter integrity. Beginning 2 h after 60 min of middle cerebral artery occlusion (MCAO), mice were randomly assigned to receive intraperitoneal docosahexaenoic acid (DHA) injections (10 mg/kg, daily for 14 days), alone or in combination with dietary fish oil (FO) supplements starting 5 days after MCAO. Sensorimotor functions, gray and white matter injury, and microglial responses were examined up to 28 days after MCAO. Our results showed that DHA and FO combined treatment-facilitated long-term sensorimotor recovery and demonstrated greater beneficial effect than DHA injections alone. Mechanistically, n-3 PUFAs not only offered direct protection on white matter components, such as oligodendrocytes, but also potentiated microglial M2 polarization, which may be important for white matter repair. Notably, the improved white matter integrity and increased M2 microglia were strongly linked to the mitigation of sensorimotor deficits after stroke upon n-3 PUFA treatments. Together, our results suggest that post-stroke DHA injections in combination with FO dietary supplement benefit white matter restoration and microglial responses, thereby dictating long-term functional improvements.

  4. Effects of quaternary ammonium chain length on the antibacterial and remineralizing effects of a calcium phosphate nanocomposite

    PubMed Central

    Zhang, Ke; Cheng, Lei; Weir, Michael D; Bai, Yu-Xing; Xu, Hockin HK

    2016-01-01

    Composites containing nanoparticles of amorphous calcium phosphate (NACP) remineralize tooth lesions and inhibit caries. A recent study synthesized quaternary ammonium methacrylates (QAMs) with chain lengths (CLs) of 3–18 and determined their effects on a bonding agent. This study aimed to incorporate these QAMs into NACP nanocomposites for the first time to simultaneously endow the material with antibacterial and remineralizing capabilities and to investigate the effects of the CL on the mechanical and biofilm properties. Five QAMs were synthesized: DMAPM (CL3), DMAHM (CL6), DMADDM (CL12), DMAHDM (CL16), and DMAODM (CL18). Each QAM was incorporated into a composite containing 20% NACP and 50% glass fillers. A dental plaque microcosm biofilm model was used to evaluate the antibacterial activity. The flexural strength and elastic modulus of nanocomposites with QAMs matched those of a commercial control composite (n = 6; P > 0.1). Increasing the CL from 3 to 16 greatly enhanced the antibacterial activity of the NACP nanocomposite (P < 0.05); further increasing the CL to 18 decreased the antibacterial potency. The NACP nanocomposite with a CL of 16 exhibited biofilm metabolic activity and acid production that were 10-fold lesser than those of the control composite. The NACP nanocomposite with a CL of 16 produced 2-log decreases in the colony-forming units (CFU) of total microorganisms, total streptococci, and mutans streptococci. In conclusion, QAMs with CLs of 3–18 were synthesized and incorporated into an NACP nanocomposite for the first time to simultaneously endow the material with antibacterial and remineralization capabilities. Increasing the CL reduced the metabolic activity and acid production of biofilms and caused a 2-log decrease in CFU without compromising the mechanical properties. Nanocomposites exhibiting strong anti-biofilm activity, remineralization effects, and mechanical properties are promising materials for tooth restorations that inhibit

  5. Effect of nano-hydroxyapatite concentration on remineralization of initial enamel lesion in vitro.

    PubMed

    Huang, S B; Gao, S S; Yu, H Y

    2009-06-01

    The purpose of the research was to determine the effect of nano-hydroxyapatite concentrations on initial enamel lesions under dynamic pH-cycling conditions. Initial enamel lesions were prepared in bovine enamel with an acidic buffer. NaF (positive control), deionized water (negative control) and four different concentrations of nano-hydroxyapatite (1%, 5%, 10% and 15% wt%) were selected as the treatment agents. Surface microhardness (SMH) measurements were performed before/after demineralization and after 3, 6, 9 and 12 days of application, and the percentage surface microhardness recovery (%SMHR) was calculated. The specimens were then examined by a scanning electron microscope. The %SMHR in nano-hydroxyapatite groups was significantly greater than that of negative control. When the concentration of nano-HA was under 10%, SMH and %SMHR increased with increasing nano-hydroxyapatite concentrations. There were no significant differences between the 10% and 15% groups at different time periods in the pH-cycling. The SEM analysis showed that nano-hydroxyapatite particles were regularly deposited on the cellular structure of the demineralized enamel surface, which appeared to form new surface layers. It was concluded that nano-hydroxyapatite had the potential to remineralize initial enamel lesions. A concentration of 10% nano-hydroxyapatite may be optimal for remineralization of early enamel caries.

  6. Remineralizing effect of cold plasma and/or bioglass on demineralized enamel.

    PubMed

    El-Wassefy, Noha A

    2017-01-20

    This study investigated the combining effect of cold plasma and bioglass-phosphoric acid paste on demineralized enamel. Fifty bovine incisors' enamel specimens were challenged by a demineralization solution of pH 4.47 for 72 h. Specimens were divided into five groups: (I) Control, demineralized enamel (C); (II) Demineralized enamel treated with fluoride varnish (F); (III) Cold plasma application to demineralized enamel (P); (IV) Demineralized enamel treated with bioglass paste (B); (V) Application of bioglass paste to cold plasma-treated demineralized enamel (PB). Specimens were then immersed in remineralizing solution for 24 h, before being examined with micro-computed tomography (micro-CT), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and cross-sectional micro-hardness measurement. The results showed that; treating demineralized enamel with cold plasmas before bioglass application ensued a significant high mineral volume recovery and micro-hardness of demineralized region. It can be concluded that cold plasmas may improve the remineralization of bioglass on demineralized enamel.

  7. Estimation of Particle Flux and Remineralization Rate from Radioactive Disequilibrium

    SciTech Connect

    Michael P. Bacon; Roger Francois

    2004-05-24

    Reactive radionuclides, such as the thorium isotopes, show measurable deficiencies in the oceanic water column because of their removal by chemical scavenging due to the particle flux. Measurement of the deficiency, coupled with measurement of the radionuclide concentration in particles, allows a determination of the effective particle sinking velocity. Results to date suggest that the effective particle sinking velocity is remarkably invariant with depth. This leads to the tentative suggestion that POC concentration profiles may, to a good approximation, be used directly to determine length scales for the remineralization of sinking organic matter. Further measurements are in progress to test this idea and to evaluate its limitations. Knowledge of the remineralization length scale is essential to an evaluation of the efficiency of the biological pump as a means for deep sequestering of carbon in the ocean.

  8. Recovery of crystallographic texture in remineralized dental enamel.

    PubMed

    Siddiqui, Samera; Anderson, Paul; Al-Jawad, Maisoon

    2014-01-01

    Dental caries is the most prevalent disease encountered by people of all ages around the world. Chemical changes occurring in the oral environment during the caries process alter the crystallography and microstructure of dental enamel resulting in loss of mechanical function. Little is known about the crystallographic effects of demineralization and remineralization. The motivation for this study was to develop understanding of the caries process at the crystallographic level in order to contribute towards a long term solution. In this study synchrotron X-ray diffraction combined with scanning electron microscopy and scanning microradiography have been used to correlate enamel crystallography, microstructure and mineral concentration respectively in enamel affected by natural caries and following artificial demineralization and remineralization regimes. In particular, the extent of destruction and re-formation of this complex structure has been measured. 2D diffraction patterns collected at the European Synchrotron Radiation Facility were used to quantify changes in the preferred orientation (crystallographic texture) and position of the (002) Bragg reflection within selected regions of interest in each tooth slice, and then correlated with the microstructure and local mineral mass. The results revealed that caries and artificial demineralization cause a large reduction in crystallographic texture which is coupled with the loss of mineral mass. Remineralization restores the texture to the original level seen in healthy enamel and restores mineral density. The results also showed that remineralization promotes ordered formation of new crystallites and growth of pre-existing crystallites which match the preferred orientation of healthy enamel. Combining microstructural and crystallographic characterization aids the understanding of caries and erosion processes and assists in the progress towards developing therapeutic treatments to allow affected enamel to regain

  9. Recovery of Crystallographic Texture in Remineralized Dental Enamel

    PubMed Central

    Siddiqui, Samera; Anderson, Paul; Al-Jawad, Maisoon

    2014-01-01

    Dental caries is the most prevalent disease encountered by people of all ages around the world. Chemical changes occurring in the oral environment during the caries process alter the crystallography and microstructure of dental enamel resulting in loss of mechanical function. Little is known about the crystallographic effects of demineralization and remineralization. The motivation for this study was to develop understanding of the caries process at the crystallographic level in order to contribute towards a long term solution. In this study synchrotron X-ray diffraction combined with scanning electron microscopy and scanning microradiography have been used to correlate enamel crystallography, microstructure and mineral concentration respectively in enamel affected by natural caries and following artificial demineralization and remineralization regimes. In particular, the extent of destruction and re-formation of this complex structure has been measured. 2D diffraction patterns collected at the European Synchrotron Radiation Facility were used to quantify changes in the preferred orientation (crystallographic texture) and position of the (002) Bragg reflection within selected regions of interest in each tooth slice, and then correlated with the microstructure and local mineral mass. The results revealed that caries and artificial demineralization cause a large reduction in crystallographic texture which is coupled with the loss of mineral mass. Remineralization restores the texture to the original level seen in healthy enamel and restores mineral density. The results also showed that remineralization promotes ordered formation of new crystallites and growth of pre-existing crystallites which match the preferred orientation of healthy enamel. Combining microstructural and crystallographic characterization aids the understanding of caries and erosion processes and assists in the progress towards developing therapeutic treatments to allow affected enamel to regain

  10. [Alternative hemodialysis regimens].

    PubMed

    Matos, Jorge Paulo Strogoff de; Lugon, Jocemir Ronaldo

    2010-03-01

    The mortality rate among patients on hemodialysis (HD) is extremely high. Remaining life expectancy for a patient initiating HD is only approximately one quarter of that of the general population at the same age bracket. The conventional HD regimen based on four-hour sessions three times a week was empirically established nearly four decades ago and needs to be revisited. Since the failure of the HEMO Study to demonstrate the clinical benefits of higher urea Kt/V for patients on conventional HD, an increasing interest for alternative HD regimens has emerged aiming at providing a treatment for improving survival rates. Short daily HD and long nocturnal HD stand out as the most promising alternative regimens. Economical obstacles which could hinder the clinical application of emerging knowledge in the field should be overcome.

  11. Is a split-dose regimen of 2 L polyethylene glycol plus ascorbic acid tolerable for colonoscopy in an early morning visit to a comprehensive medical check-up?

    PubMed Central

    Seo, Ji Yeon; Lee, Changhyun; Jin, Eun Hyo; Yun, Mi Hyun; Lim, Joo Hyun; Kang, Hae Yeon; Yang, Jong In; Chung, Su Jin; Yang, Sun Young; Kim, Joo Sung

    2017-01-01

    AIM To evaluate the effectiveness and tolerability of a split-dose 2 L polyethylene glycol (PEG)/ascorbic acid (AA) regimen for healthy examinees who visited for comprehensive medical check-up in the early morning. METHODS From February 2015 to March 2015, examinees of average risk who were scheduled for a colonoscopy in the morning were retrospectively enrolled. RESULTS The 189 examinees were divided into split-dose and non-split-dose groups. The adequacy of bowel preparation for the split-dose group vs the non-split-dose group was 96.8% vs 85.2%, respectively, P < 0.001, and the compliance of the last meal restriction was 74.6% vs 58.2%, respectively, P < 0.001. The sleep disturbance (P < 0.001) was more prevalent in the split-dose group, however the willingness to repeat the same preparation method (P = 0.243) was not different in both groups. The split-dose regimen was the most important factor influencing adequate bowel preparation in multivariate analysis (HR = 10.89, 95%CI: 6.53-18.17, P < 0.001). CONCLUSION A split-dose regimen of 2 L PEG/AA for an early morning colonoscopy was more effective and showed better compliance for diet restriction without any difference in satisfaction and discomfort. Introducing a split-dose regimen of 2 L PEG/AA to morning colonoscopy examinees is effective and tolerable in a comprehensive medical check-up setting. PMID:28246476

  12. N/P re-mineralization ratios across forests worldwide

    NASA Astrophysics Data System (ADS)

    Marklein, A. R.; Houlton, B. Z.

    2012-12-01

    Decomposition of leaf litter is the primary mechanism by which nutrients are recycled in forests. Forests are a sink for atmospheric CO2, but nitrogen (N) and phosphorus (P) could limit or eliminate this ecosystem service in the future. Nutrient cycling during mineralization supplies the vast majority of nutrients to enable forest growth. Therefore, elucidating patterns by which organic N and P are mineralized by decomposing organisms or immobilized in microbial biomass is crucial to establishing controls on plant nutrient availability. Here, we compare re-mineralization N/P ratios to the stoichiometry of the initial material. We performed a meta-analysis of N and P mineralization from leaves and needles in forest ecosystems and included 112 studies, 511 litterbag sequences, and 3225 observations. Of the compiled data, net mineralization occurred in 54 studies, 372 litterbag sequences, and 1308 observations. We compare re-mineralization ratios across temperate and tropical forest systems to elucidate patterns across latitudes. We report strong and systematic regularities between decomposing litter N/P and the N/P of re-mineralization across global forests. Overall, the N/P of mineralization scales at a slope close to unity (slope = 1.4, R2=0.53, n=372), with a tendency toward higher N/P in tropical vs. temperate forests. The N/P of tropical forest re-mineralization is equal to 30/1 (R2=0.55; n=691), corresponding with the high N/P of plant foliage and litter within this biome. In contrast, the N/P of mineralization is equal to 5/1 in temperate forests (R2=0.34; n=617). A modal anomaly analysis further reveals the central tendency of mineralization N/P on that of litter, with departures from the average case tending toward a lower N/P of mineralization compared to litter substrates. These deviations suggest the potential for preferential N retention or enhanced P mineralization, or both, as opposed to more rapid N releases from decomposing organic matter. The

  13. Quantifying the remineralization of artificial caries lesions using PS-OCT

    NASA Astrophysics Data System (ADS)

    Jones, Robert S.; Fried, Daniel

    2006-02-01

    New optical imaging methods are needed to determine whether caries lesions (tooth decay) are active and progressing or have become remineralized and arrested and are no longer progressing. The objective of this study was to use Polarization Sensitive Optical Coherence Tomography (PS-OCT) to image the fluoride enhanced remineralization of artificial enamel lesions. Artificial lesions were created by an acetate buffer on smooth enamel surfaces and were exposed for 20 days to a 2 ppm fluoride containing remineralization solution. PS-OCT images revealed the presence of a low scattering surface zone after the artificial lesions were remineralized. These samples displayed intact nondepolarizing surface zones when analyzed with Polarized Light Microscopy (PLM). No statistical difference in lesion depth before and after remineralization was found with both PS-OCT and PLM. The remineralized lesions showed a significant decrease in the overall integrated reflectivity compared with the demineralized lesions. Digital Microradiography confirmed the increase in mineral volume of the remineralized surface zone. This study determined that PS-OCT can image the restoration of the surface zone enamel after fluoride-enhanced remineralization of artificial in vitro dental caries.

  14. In Vitro Remineralization Effects of Grape Seed Extract on Artificial Root Caries

    PubMed Central

    Xie, Qian; Bedran-Russo, Ana Karina; Wu, Christine D.

    2008-01-01

    Grape seed extract (GSE) contains Proanthocyanidin (PA), which has been reported to strengthen collagen-based tissues by increasing collagen cross-links. We used an in vitro pH-cycling model to evaluate the effect of GSE on the remineralization of artificial root caries. Sound human teeth fragments obtained from the cervical portion of the root were stored in a demineralization solution for 96 hr at 37°C to induce artificial root caries lesions. The fragments were then divided into three treatment groups including: 6.5% GSE, 1,000 ppm fluoride (NaF), and a control (no treatment). The demineralized samples were pH-cycled through treatment solutions, acidic buffer and neutral buffer for 8 days at 6 cycles per day. The samples were subsequently evaluated using a microhardness tester; polarized light microscopy (PLM) and confocal laser scanning microscopy (CLSM). Data were analyzed using ANOVA and Fisher’s tests (p<0.05). GSE and fluoride significantly increased the microhardness of the lesions (p<0.05) when compared to a control group. PLM data revealed a significantly thicker mineral precipitation band on the surface layer of the GSE treated lesions when compared to the other groups (p>0.05), which was confirmed by CLSM. We concluded that grape seed extract positively affects the demineralization and/or remineralization processes of artificial root caries lesions, most likely through a different mechanism than that of Fluoride. Grape seed extract may be a promising natural agent for non-invasive root caries therapy. PMID:18819742

  15. In vitro remineralization of enamel by polymeric amorphous calcium phosphate composite: Quantitative micro-radiographic study

    PubMed Central

    Langhorst, S.E.; O'Donnell, J.N.R.; Skrtic, D.

    2009-01-01

    Objective: This study explores the efficacy of an experimental orthodontic amorphous calcium phosphate (ACP) composite to remineralize in vitro subsurface enamel lesions microradiographically similar to those seen in early caries. Methods: Lesions were artificially created in extracted human molars. Single tooth sections a minimum of 120 μm thick were cut and individually placed in holders exposing only the carious enamel surface. The exposed surfaces were either left untreated (control) or coated with a 1 mm thick layer of the experimental ACP composite (mass fraction 40 % zirconiahybridized ACP and 60 % photo-activated resin), or a commercial fluoride-releasing orthodontic cement. The composite-coated sections were then photo-cured and microradiographic images were taken of all three groups of specimens before the treatment. Specimens were then cyclically immersed in demineralizing and remineralizing solutions for one month at 37 °C to simulate the pH changes occurring in the oral environment. Microradiographs of all specimens were taken before and after treatment. Results: Quantitative digital image analysis of matched areas from the contact microradiographs taken before and after treatment indicated higher mineral recovery with ACP composites compared to the commercial orthodontic F-releasing cement (14.4 % vs. 4.3 %, respectively), while the control specimens showed an average of 55.4 % further demineralization. Significance: Experimental ACP composite efficiently established mineral ion transfer throughout the body of the lesions and restored the mineral lost due to acid attack. It can be considered a useful adjuvant for the control of caries in orthodontic applications. PMID:19215975

  16. Effects of processed cheese on human plaque pH and demineralization and remineralization.

    PubMed

    Jensen, M E; Wefel, J S

    1990-10-01

    This two-part study was undertaken to examine the effects of processed cheese on human plaque pH and de- and remineralization of enamel and root lesions in a human in situ caries model system. In the first part of the study the selected processed cheese (Kraft American Singles Processed Cheese Food) was eaten alone and followed by a 10% sucrose rinse after the acidogenicity of the plaque was demonstrated. A 10% sucrose rinse alone resulted in a mean minimum pH of 4.26. The cheese alone showed a mean minimum pF of 6.32 and cheese followed by sucrose resulted in a mean minimum pH of 6.48. The plaque pH of cheese eaten alone stayed at pH above 5.7 (the "safe for teeth" level). Cheese consumption also prevented the acid challenge when followed by sucrose. The second part of the study utilized the thin-sections of artificially created caries-like lesions on enamel and root, and sound root sections. One-month periods were used in a cross-over design to examine the effect of eating the cheese q.i.d. Polarized light microscopy was used to determine changes in the size of lesion areas. The addition of the processed cheese to the diet resulted in statistically significant reductions in enamel lesion size as well as a reduction in progression of root lesions. Lesions created on the sound root surfaces were approximately one-third the size of those created during the control period. This study indicates that processed cheese is hypoacidogenic, anti-acidogenic, and prevents demineralization as well as enhances remineralization.

  17. Demineralization–remineralization dynamics in teeth and bone

    PubMed Central

    Abou Neel, Ensanya Ali; Aljabo, Anas; Strange, Adam; Ibrahim, Salwa; Coathup, Melanie; Young, Anne M; Bozec, Laurent; Mudera, Vivek

    2016-01-01

    Biomineralization is a dynamic, complex, lifelong process by which living organisms control precipitations of inorganic nanocrystals within organic matrices to form unique hybrid biological tissues, for example, enamel, dentin, cementum, and bone. Understanding the process of mineral deposition is important for the development of treatments for mineralization-related diseases and also for the innovation and development of scaffolds. This review provides a thorough overview of the up-to-date information on the theories describing the possible mechanisms and the factors implicated as agonists and antagonists of mineralization. Then, the role of calcium and phosphate ions in the maintenance of teeth and bone health is described. Throughout the life, teeth and bone are at risk of demineralization, with particular emphasis on teeth, due to their anatomical arrangement and location. Teeth are exposed to food, drink, and the microbiota of the mouth; therefore, they have developed a high resistance to localized demineralization that is unmatched by bone. The mechanisms by which demineralization–remineralization process occurs in both teeth and bone and the new therapies/technologies that reverse demineralization or boost remineralization are also scrupulously discussed. Technologies discussed include composites with nano- and micron-sized inorganic minerals that can mimic mechanical properties of the tooth and bone in addition to promoting more natural repair of surrounding tissues. Turning these new technologies to products and practices would improve health care worldwide. PMID:27695330

  18. Demineralization-remineralization dynamics in teeth and bone.

    PubMed

    Abou Neel, Ensanya Ali; Aljabo, Anas; Strange, Adam; Ibrahim, Salwa; Coathup, Melanie; Young, Anne M; Bozec, Laurent; Mudera, Vivek

    Biomineralization is a dynamic, complex, lifelong process by which living organisms control precipitations of inorganic nanocrystals within organic matrices to form unique hybrid biological tissues, for example, enamel, dentin, cementum, and bone. Understanding the process of mineral deposition is important for the development of treatments for mineralization-related diseases and also for the innovation and development of scaffolds. This review provides a thorough overview of the up-to-date information on the theories describing the possible mechanisms and the factors implicated as agonists and antagonists of mineralization. Then, the role of calcium and phosphate ions in the maintenance of teeth and bone health is described. Throughout the life, teeth and bone are at risk of demineralization, with particular emphasis on teeth, due to their anatomical arrangement and location. Teeth are exposed to food, drink, and the microbiota of the mouth; therefore, they have developed a high resistance to localized demineralization that is unmatched by bone. The mechanisms by which demineralization-remineralization process occurs in both teeth and bone and the new therapies/technologies that reverse demineralization or boost remineralization are also scrupulously discussed. Technologies discussed include composites with nano- and micron-sized inorganic minerals that can mimic mechanical properties of the tooth and bone in addition to promoting more natural repair of surrounding tissues. Turning these new technologies to products and practices would improve health care worldwide.

  19. Effects of common dental materials used in preventive or operative dentistry on dentin permeability and remineralization.

    PubMed

    Sauro, Salvatore; Thompson, Ian; Watson, Timothy F

    2011-01-01

    The aim of this study was to evaluate the dentin remineralization induced by bioactive substances contained in common dental materials used in preventive and operative dentistry. Several materials were applied on human dentin segments. Dentin permeability was quantified using a fluid filtration system working at 20 cm H(2)O. Micro-Raman, SEM-EDX, and microhardness calculation were used to evaluate changes in the mineralization of dentin. Dentin treated with the prophylactic materials showed different dentin permeability values, in particular subsequent to immersion in remineralizing solutions (RSS). The bioactive glass (Sylc) was the only substance able to reduce dentin permeability after immersion in remineralizing solution and to show hydroxyapatite precipitation as a sign of dentin remineralization. The reduction in dentin permeability obtained after the application of the other prophylactic materials used in this study was due to the presence of the remnant material in the dentinal tubules, with no remineralization effect after storage in remineralizing solution. In conclusion, the results indicated that bioactive glass prophy powder may induce immediate remineralization of dentin.

  20. Role of enamel deminerlization and remineralization on microtensile bond strength of resin composite

    PubMed Central

    Rizvi, Abbas; Zafar, Muhammad S.; Al-Wasifi, Yasser; Fareed, Wamiq; Khurshid, Zohaib

    2016-01-01

    Objective: This study is aimed to establish the microtensile bond strength of enamel following exposure to an aerated drink at various time intervals with/without application of remineralization agent. In addition, degree of remineralization and demineralization of tooth enamel has been assessed using polarized light microscopy. Materials and Methods: Seventy extracted human incisors split into two halves were immersed in aerated beverage (cola drink) for 5 min and stored in saliva until the time of microtensile bond testing. Prepared specimens were divided randomly into two study groups; remineralizing group (n = 70): specimens were treated for remineralization using casein phosphopeptides and amorphous calcium phosphate (CPP-ACP) remineralization agent (Recaldent™; GC Europe) and control group (n = 70): no remineralization treatment; specimens were kept in artificial saliva. All specimens were tested for microtensile bond strength at regular intervals (1 h, 1 days, 2 days, 1 week, and 2 weeks) using a universal testing machine. The results statistically analyzed (P = 0.05) using two-way ANOVA test. Results: Results showed statistically significant increase in bond strength in CPP-ACP tested group (P < 0.05) at all-time intervals. The bond strength of remineralizing group samples at 2 days (~13.64 megapascals [MPa]) is comparable to that of control group after 1 week (~12.44 MPa). Conclusions: CPP-ACP treatment of teeth exposed to an aerated drink provided significant increase in bond strength at a shorter interval compared to teeth exposed to saliva alone. PMID:27403057

  1. Current technology and techniques in re-mineralization of white spot lesions: A systematic review

    NASA Astrophysics Data System (ADS)

    Podray, Susan S.

    White Spot lesions are a common iatrogenic occurrence on patients who are treated with fixed orthodontic appliances. There is a dynamic chemical interaction between enamel and saliva at the tooth surface that allow a lesion to have phase changes involving demineralization of enamel and reminerlization. This is due to calcium and phosphate dissolved in saliva that is deposited onto the tooth surface or removed depending on the surrounding pH. Caseinphosphopeptide-amorphous calcium phosphate (CPP-ACP) is gaining popularity in dentistry as a way to increase the available level of calcium and phosphate in plaque and saliva to improve the chemical gradient so that if favors reminerlization. The aim of our investigation is to search the available current literature and formulate a recommendation for use of CPP-ACP in orthodontics. Publications from the following electronic databases were searched: PubMed, Web of Science, Cochrane Library and Science Direct. Searches from August 2010 to April 1st 2012 were performed under the terms "MI Paste OR Recaldent OR caseinphosphopeptide-amorphous calcium phosphate OR CPP-ACP or tooth mousse". The searches yielded 155 articles, These were reviewed for relevance based on inclusion and exclusion criteria. Articles with inappropriate study design or no outcome measures at both baseline and end point were also excluded. 13 articles were deemed of relevance with a high quality study design and were included in this study for evaluation. The current literature suggests a preventative treatment regimen in which MI Paste Plus is used. It should be delivered once daily prior to bed after oral hygiene for 3 minutes in a fluoride tray, throughout orthodontic treatment. It should be recommended for high risk patients determined by poor oral hygiene, as seen by the inability to remove plaque from teeth and appliances. This protocol may prevent or assist in the remineralization of enamel white spot lesions during and after orthodontic treatment.

  2. Snowball Earth prevention by dissolved organic carbon remineralization.

    PubMed

    Peltier, W Richard; Liu, Yonggang; Crowley, John W

    2007-12-06

    The 'snowball Earth' hypothesis posits the occurrence of a sequence of glaciations in the Earth's history sufficiently deep that photosynthetic activity was essentially arrested. Because the time interval during which these events are believed to have occurred immediately preceded the Cambrian explosion of life, the issue as to whether such snowball states actually developed has important implications for our understanding of evolutionary biology. Here we couple an explicit model of the Neoproterozoic carbon cycle to a model of the physical climate system. We show that the drawdown of atmospheric oxygen into the ocean, as surface temperatures decline, operates so as to increase the rate of remineralization of a massive pool of dissolved organic carbon. This leads directly to an increase of atmospheric carbon dioxide, enhanced greenhouse warming of the surface of the Earth, and the prevention of a snowball state.

  3. Terahertz pulsed imaging study to assess remineralization of artificial caries lesions

    NASA Astrophysics Data System (ADS)

    Churchley, David; Lynch, Richard J. M.; Lippert, Frank; O'Bryan Eder, Jennifer Susan; Alton, Jesse; Gonzalez-Cabezas, Carlos

    2011-02-01

    We compare terahertz-pulsed imaging (TPI) with transverse microradiography (TMR) and microindentation to measure remineralization of artificial caries lesions. Lesions are formed in bovine enamel using a solution of 0.1 M lactic acid/0.2% Carbopol C907 and 50% saturated with hydroxyapatite adjusted to pH 5.0. The 20-day experimental protocol consists of four 1 min treatment periods with dentifrices containing 10, 675, 1385, and 2700 ppm fluoride, a 4-h/day acid challenge, and, for the remaining time, specimens are stored in a 50:50 pooled human/artificial saliva mixture. Each specimen is imaged at the focal point of the terahertz beam (data-point spacing = 50 μm). The time-domain data are used to calculate the refractive index volume percent profile throughout the lesion, and the differences in the integrated areas between the baseline and post-treatment profiles are used to calculate ΔΔZ(THz). In addition, the change from baseline in both the lesion depth and the intensity of the reflected pulse from the air/enamel interface is determined. Statistically significant Pearson correlation coefficients are observed between TPI and TMR/microindentation (P < 0.05). We demonstrate that TPI has potential as a research tool for hard tissue imaging.

  4. Shallow Remineralization in the Sargasso Sea Estimated from Seasonal Variations in Oxygen and Dissolved Inorganic Carbon

    NASA Technical Reports Server (NTRS)

    Ono, S.; Ennyu, A.; Najjar, R. G.; Bates, N.

    1998-01-01

    A diagnostic model of the mean annual cycles of dissolved inorganic carbon (DIC) and oxygen below the mixed layer at the Bermuda Atlantic Time-series Study (BATS) site is presented and used to estimate organic carbon remineralization in the seasonal thermocline. The model includes lateral and vertical advection as well as vertical, diffusion. Very good agreement is found for the remineralization estimates based on oxygen and DIC. Net remineralization averaged from mid-spring to early fall is found to be a maximum between 120 and 140 in. Remineralization integrated between 100 (the compensation depth) and 250 m during this period is estimated to be about 1 mol C/sq m. This flux is consistent with independent estimates of the loss of particulate and dissolved organic carbon.

  5. Solution activity product (KFAP) and simultaneous demineralization-remineralization in bovine tooth enamel and hydroxyapatite pellets

    SciTech Connect

    Fox, J.L.; Iyer, B.V.; Higuchi, W.I.; Hefferren, J.J.

    1983-11-01

    The effects of changing the ion activity product of the remineralization solution at pH 4.5 (pKFAP 108-118) on the remineralization behavior of demineralized bovine tooth enamel and hydroxyapatite pellets have been studied. Solutions containing calcium-4.5, phosphate, and fluoride in acetate buffers were used. The /sup 45/Ca/F molar ratios indicated the formation of fluoridated hydroxyapatite in the enamel or the pellet when the pKFAP values for remineralizing solutions were less than 112. When the pKFAP values were greater than 112, the /sup 45/Ca/F ratios were found to be much less than 5. Also, when the pKFAP values were large (greater than 112), the remineralization patterns based on the fluoride distribution in the tooth (or pellet) were found to be different than when the pKFAP values were small (less than 112). The hypothesis that a pKFAP value of 112 is the demarcation between remineralization only and simultaneous dissolution-remineralization has been proposed based on these results.

  6. Biomimetic remineralization of human enamel in the presence of polyamidoamine dendrimers in vitro.

    PubMed

    Chen, Liang; Yuan, He; Tang, Bei; Liang, Kunneng; Li, Jiyao

    2015-01-01

    Poly(amidoamine) (PAMAM) dendrimers, known as artificial proteins, have unique and well-defined molecular size and structure. It has previously been used to mimic protein-crystal interaction during biomineralization. In this study, generation 4.5 (4.5G) PAMAM with carboxylic acid (PAMAM-COOH) was synthesized and utilized to remineralize the surface of etched enamel in vitro. Using confocal laser scanning microscopy, Fourier transform infrared spectroscopy, X-ray diffraction analysis and scanning electron microscopy we observed that 4.5G PAMAM-COOH can be absorbed on the etched enamel surface and that it can induce the formation of hydroxyapatite crystals with the same orientation as that of the enamel prisms on longitudinal and transversal enamel surfaces. The self-assembly behavior of PAMAM in the mineralization solution was also investigated and the result showed that 4.5G PAMAM can assemble to microribbon structure similar to the behavior of amelogenins. Therefore, we concluded that 4.5G PAMAM-COOH assemblies can act as the organic template on enamel surface and in mineralization solution to control the nucleation site and morphology of new-grown crystals to form the biomimetic structure of human enamel, which may open a new way for repairing damaged enamel.

  7. Methods for Biomimetic Remineralization of Human Dentine: A Systematic Review

    PubMed Central

    Cao, Chris Ying; Mei, May Lei; Li, Quan-Li; Lo, Edward Chin Man; Chu, Chun Hung

    2015-01-01

    This study aimed to review the laboratory methods on biomimetic remineralization of demineralized human dentine. A systematic search of the publications in the PubMed, TRIP, and Web of Science databases was performed. Titles and abstracts of initially identified publications were screened. Clinical trials, reviews, non-English articles, resin-dentine interface studies, hybrid layer studies, hybrid scaffolds studies, and irrelevant studies were excluded. The remaining papers were retrieved with full texts. Manual screening was conducted on the bibliographies of remaining papers to identify relevant articles. A total of 716 studies were found, and 690 were excluded after initial screening. Two articles were identified from the bibliographies of the remaining papers. After retrieving the full text, 23 were included in this systematic review. Sixteen studies used analogues to mimic the functions of non-collagenous proteins in biomineralization of dentine, and four studies used bioactive materials to induce apatite formation on demineralized dentine surface. One study used zinc as a bioactive element, one study used polydopamine, and another study constructed an agarose hydrogel system for biomimetic mineralization of dentine. Many studies reported success in biomimetic mineralization of dentine, including the use of non-collagenous protein analogues, bioactive materials, or elements and agarose hydrogel system. PMID:25739078

  8. Methods for biomimetic remineralization of human dentine: a systematic review.

    PubMed

    Cao, Chris Ying; Mei, May Lei; Li, Quan-Li; Lo, Edward Chin Man; Chu, Chun Hung

    2015-03-02

    This study aimed to review the laboratory methods on biomimetic remineralization of demineralized human dentine. A systematic search of the publications in the PubMed, TRIP, and Web of Science databases was performed. Titles and abstracts of initially identified publications were screened. Clinical trials, reviews, non-English articles, resin-dentine interface studies, hybrid layer studies, hybrid scaffolds studies, and irrelevant studies were excluded. The remaining papers were retrieved with full texts. Manual screening was conducted on the bibliographies of remaining papers to identify relevant articles. A total of 716 studies were found, and 690 were excluded after initial screening. Two articles were identified from the bibliographies of the remaining papers. After retrieving the full text, 23 were included in this systematic review. Sixteen studies used analogues to mimic the functions of non-collagenous proteins in biomineralization of dentine, and four studies used bioactive materials to induce apatite formation on demineralized dentine surface. One study used zinc as a bioactive element, one study used polydopamine, and another study constructed an agarose hydrogel system for biomimetic mineralization of dentine. Many studies reported success in biomimetic mineralization of dentine, including the use of non-collagenous protein analogues, bioactive materials, or elements and agarose hydrogel system.

  9. Organic nutrient enrichment in the oligotrophic ocean: Impacts on remineralization, carbon sequestration, and community structure

    NASA Astrophysics Data System (ADS)

    Mackey, K. R.; Paytan, A.; Post, A. F.

    2007-12-01

    In oligotrophic seas where inorganic nitrogen (N) and phosphorus (P) are below the limits of detection, organic forms of these nutrients may constitute greater than 90% of the total N and P in the euphotic zone. The combined enzymatic activity of phytoplankton and heterotrophic bacteria determines the rate of nutrient remineralization, thereby influencing phytoplankton growth rates and carbon sequestration in these regions. In this study we investigated the effects of fertilization with ammonium (NH4), nitrate (NO3), nitrite (NO2), and phosphate (PO4) as well as various forms of organic N (urea, glycine) and P (deoxyribonucleic acid, 2- aminoethyl phosphonic acid, phytic acid) on the growth and taxonomic composition of the phytoplankton community in the Gulf of Aqaba, Red Sea. The impacts of these changes on nutrient cycling and biological assimilation were also assessed. Organic N additions led to phytoplankton growth when given together with PO4, yielding 2-3 fold increases in chlorophyll a (Chl a) and cell density relative to initial levels. Moreover, our results show that addition of NH4 or NO3 led to accumulation of extra-cellular NO2, suggesting that incomplete assimilatory reduction of NO3 by phytoplankton as well as chemoautotrophic oxidation of NH4 by ammonium oxidizing microbes contributed to NO2 formation. These findings conflict with earlier studies in the Gulf that attributed NO2 formation solely to the phytoplankton community. Organic P additions also led to 2-3 fold increases in Chl a and cell density relative to initial levels when given together with NH4 and NO3. Compared to other P additions, DNA led to the rapid accumulation of extra-cellular PO4, indicating substantial nucleotidase activity in excess of the amount needed to meet phytoplankton growth requirements. These results show the importance and interconnectivity of phytoplankton and heterotrophic bacteria communities in contributing to nutrient cycling and carbon sequestration in

  10. Nutritional Evaluation and Optimisation in Neonates: a randomized, double-blind controlled trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition12

    PubMed Central

    Liu, Xinxue; Babalis, Daphne; Doré, Caroline J; Warwick, Jane; Bell, Jimmy; Thomas, Louise; Ashby, Deborah; Durighel, Giuliana; Ederies, Ash; Yanez-Lopez, Monica; Modi, Neena

    2016-01-01

    Background: Parenteral nutrition is central to the care of very immature infants. Current international recommendations favor higher amino acid intakes and fish oil–containing lipid emulsions. Objective: The aim of this trial was to compare 1) the effects of high [immediate recommended daily intake (Imm-RDI)] and low [incremental introduction of amino acids (Inc-AAs)] parenteral amino acid delivery within 24 h of birth on body composition and 2) the effect of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (SMOF) with that of soybean oil (SO)-based lipid emulsion on intrahepatocellular lipid (IHCL) content. Design: We conducted a 2-by-2 factorial, double-blind, multicenter randomized controlled trial. Results: We randomly assigned 168 infants born at <31 wk of gestation. We evaluated outcomes at term in 133 infants. There were no significant differences between Imm-RDI and Inc-AA groups for nonadipose mass [adjusted mean difference: 1.0 g (95% CI: −108, 111 g; P = 0.98)] or between SMOF and SO groups for IHCL [adjusted mean SMOF:SO ratio: 1.1 (95% CI: 0.8, 1.6; P = 0.58]. SMOF does not affect IHCL content. There was a significant interaction (P = 0.05) between the 2 interventions for nonadipose mass. There were no significant interactions between group differences for either primary outcome measure after adjusting for additional confounders. Imm-RDI infants were more likely than Inc-AA infants to have blood urea nitrogen concentrations >7 mmol/L or >10 mmol/L, respectively (75% compared with 49%, P < 0.01; 49% compared with 18%, P < 0.01). Head circumference at term was smaller in the Imm-RDI group [mean difference: −0.8 cm (95% CI: −1.5, −0.1 cm; P = 0.02)]. There were no significant differences in any prespecified secondary outcomes, including adiposity, liver function tests, incidence of conjugated hyperbilirubinemia, weight, length, mortality, and brain volumes. Conclusion

  11. Early season mesopelagic carbon remineralization and transfer efficiency in the naturally iron-fertilized Kerguelen area

    NASA Astrophysics Data System (ADS)

    Jacquet, S. H. M.; Dehairs, F.; Cavagna, A. J.; Planchon, F.; Monin, L.; André, L.; Closset, I.; Cardinal, D.

    2014-06-01

    We report on the zonal variability of mesopelagic particulate organic carbon) remineralization and deep carbon transfer potential during the Kerguelen Ocean and Plateau compared Study 2 expedition (KEOPS 2; October-November 2011) in an area of the Polar Front supporting recurrent massive blooms from natural Fe fertilization. Mesopelagic carbon remineralization was assessed using the excess, non-lithogenic particulate barium (Baxs) inventories in mesopelagic waters and compared with surface primary and export productions. Results for this early season study are compared with results obtained earlier (2005; KEOPS 1) for the same area during summer. For the Kerguelen plateau (A3 site) we observe a similar functioning of the mesopelagic ecosystem during both seasons (spring and summer), with less that 30% of carbon exported from the upper 150 m being remineralized in the mesopelagic column (150-400 m). For deeper stations (> 2000 m) located on the margin, inside a Polar Front meander, as well as in the vicinity of the Polar Front, east of Kerguelen, remineralization in the upper 400 m in general represents > 30% of carbon export, but when considering the upper 800 m, in some cases, the entire flux of exported carbon is remineralized. It appears that above the plateau (A3 site) mesopelagic remineralization is not a major barrier to the transfer of organic matter to the sea-floor (close to 500 m). There the efficiency of carbon sequestration into the bottom waters (> 400 m) reached up to 87% of the carbon exported from the upper 150 m. In contrast, at the deeper locations mesopelagic remineralization clearly limits the sequestration of carbon to depths > 400 m. For sites at the margin of the plateau (station E-4W) and the Polar front (station F-L), mesopelagic remineralization even exceeds upper 150 m export, resulting in a null sequestration efficiency to depths > 800 m. In the Polar Front meander, where successive stations form a time series, the capacity of the

  12. Remineralization potential of nano-hydroxyapatite on initial enamel lesions: an in vitro study.

    PubMed

    Huang, S; Gao, S; Cheng, L; Yu, H

    2011-01-01

    The application of nano-hydroxyapatite (HA) in the repair of early caries lesion has received considerable attention. Neither the effects of the size of HA nor the effects of the effective pH range of nano-HA on remineralization have been investigated comprehensively, and the protective mechanism is still open for debate. To address these factors, the remineralization effect of nano-HA on demineralized bovine enamel is investigated under pH cycling conditions through surface and cross-sectional microhardness (CSMH) tests and polarized light microscopy (PLM). The percentage of surface microhardness recovery and integrated mineral loss obtained from CSMH tests demonstrated that nano-HA provides better remineralization than micro-HA. However, detailed investigation using CSMH tests and PLM indicated that nano-HA helped mineral deposition predominantly in the outer layer of the lesion and only had a limited capacity to reduce lesion depth. Nevertheless, the remineralization effect of nano-HA increased significantly when the pH was less than 7.0. Clearly, nano-HA has potential as an effective repair material and anticaries agent. Our findings also suggest that both the particle- and ion-mediated remineralization pathways in nano-HA may contribute to the repair of demineralized enamel.

  13. Investigation on the remineralization effect of arginine toothpaste for early enamel caries: nanotribological and nanomechanical properties

    NASA Astrophysics Data System (ADS)

    Yu, Ping; Arola, Dwayne D.; Min, Jie; Yu, Dandan; Xu, Zhou; Li, Zhi; Gao, Shanshan

    2016-11-01

    Remineralization is confirmed as a feasible method to restore early enamel caries. While there is evidence that the 8% arginine toothpaste has a good remineralization effect by increasing surface microhardness, the repair effect on wear-resistance and nanomechanical properties still remains unclear. Therefore, this research was conducted to reveal the nanotribological and nanomechanical properties changes of early caries enamel after remineralized with arginine toothpaste. Early enamel caries were created in bovine enamel blocks, and divided into three groups according to the treatment solutions: distilled and deionized water (DDW group), arginine toothpaste slurry (arginine group) and fluoride toothpaste slurry (fluoride group). All of the samples were subjected to pH cycling for 12 d. The nanotribological and nanomechanical properties were evaluated via the nanoscratch and nanoindentation tests. The wear depth and scratch morphology were observed respectively by scanning probe microscopic (SPM) and scanning electron microscopy (SEM). Finally, x-ray photoelectron spectroscopy (XPS) was used for element analysis of remineralized surfaces. Results showed that the wear depth of early caries enamel decreased after remineralization treatment and both the nanohardness and elastic modulus increased. Compared with the fluoride group, the arginine group exhibited higher nanohardness and elastic modulus with higher levels of calcium, fluoride, nitrogen and phosphorus; this group also underwent less wear and related damage. Overall, the synergistic effect of arginine and fluoride in arginine toothpaste achieves better nanotribological and nanomechanical properties than the single fluoride toothpaste, which could have significant impact on fight against early enamel caries.

  14. Dentifrices, mouthwashes, and remineralization/caries arrestment strategies

    PubMed Central

    Zero, Domenick T

    2006-01-01

    While our knowledge of the dental caries process and its prevention has greatly advanced over the past fifty years, it is fair to state that the management of this disease at the level of the individual patient remains largely empirical. Recommendations for fluoride use by patients at different levels of caries risk are mainly based on the adage that more is better. There is a general understanding that the fluoride compound, concentration, frequency of use, duration of exposure, and method of delivery can influence fluoride efficacy. Two important factors are (1) the initial interaction of relatively high concentrations of fluoride with the tooth surface and plaque during application and (2) the retention of fluoride in oral fluids after application. Fluoride dentifrices remain the most widely used method of delivering topical fluoride. The efficacy of this approach in preventing dental caries is beyond dispute. However, the vast majority of currently marketed dentifrice products have not been clinically tested and have met only the minimal requirements of the FDA monograph using mainly laboratory testing and animal caries testing. Daily use of fluoride dental rinses as an adjunct to fluoride dentifrice has been shown to be clinically effective as has biweekly use of higher concentration fluoride rinses. The use of remineralizing agents (other than fluoride), directed at reversing or arresting non-cavitated lesions, remains a promising yet largely unproven strategy. High fluoride concentration compounds, e.g., AgF, Ag(NH3)2F, to arrest more advanced carious lesions with and without prior removal of carious tissue are being used in several countries as part of the Atraumatic Restorative Treatment (ART) approach. Most of the recent innovations in oral care products have been directed toward making cosmetic marketing claims. There continues to be a need for innovation and collaboration with other scientific disciplines to fully understand and prevent dental caries

  15. Evaluation of the efficacy, tolerability, and safety of an over-the-counter acne regimen containing benzoyl peroxide and salicylic acid in subjects with acne.

    PubMed

    Kircik, Leon H; Gwazdauskas, Jennifer; Butners, Victoria; Eastern, Joseph; Green, Lawrence J

    2013-03-01

    Benzoyl peroxide (BPO) is a widely used over-the-counter (OTC) topical acne treatment often used in combination with salicylic acid (SA) to achieve better comedone control than that achieved with BPO alone. MaxClarity™ is an OTC acne treatment system comprising BPO and SA in an aqueous foam delivery vehicle, VersaFoam AF™. This paper describes 2 open-label, single-arm studies conducted to assess the efficacy, safety, tolerability, and patient preference of MaxClarity in the treatment of mild, moderate, and severe acne. Subjects applied MaxClarity twice daily for 8 weeks in study 402 and for 12 weeks in study 405. Reductions in all lesion types were seen throughout both studies. At week 8 (study 402), there was a mean reduction from baseline of -56.9 ± 32.7% in total lesions in subjects with mild, moderate, or severe acne. At week 12 (study 405), there was a reduction from baseline of -61.6 ± 22.0% in total lesions in subjects with moderate or severe acne. Overall, both studies demonstrated that MaxClarity is a generally well tolerated and effective treatment for mild, moderate, and severe acne.

  16. Remineralization of particulate organic carbon in an ocean oxygen minimum zone

    PubMed Central

    Cavan, E. L.; Trimmer, M.; Shelley, F.; Sanders, R.

    2017-01-01

    Biological oceanic processes, principally the surface production, sinking and interior remineralization of organic particles, keep atmospheric CO2 lower than if the ocean was abiotic. The remineralization length scale (RLS, the vertical distance over which organic particle flux declines by 63%, affected by particle respiration, fragmentation and sinking rates) controls the size of this effect and is anomalously high in oxygen minimum zones (OMZ). Here we show in the Eastern Tropical North Pacific OMZ 70% of POC remineralization is due to microbial respiration, indicating that the high RLS is the result of lower particle fragmentation by zooplankton, likely due to the almost complete absence of zooplankton particle interactions in OMZ waters. Hence, the sensitivity of zooplankton to ocean oxygen concentrations can have direct implications for atmospheric carbon sequestration. Future expansion of OMZs is likely to increase biological ocean carbon storage and act as a negative feedback on climate change. PMID:28322218

  17. Remineralization of initial enamel caries in vitro using a novel peptide based on amelogenin

    NASA Astrophysics Data System (ADS)

    Li, Danxue; Lv, Xueping; Tu, Huanxin; Zhou, Xuedong; Yu, Haiyang; Zhang, Linglin

    2015-09-01

    Dental caries is the most common oral disease with high incidence, widely spread and can seriously affect the health of oral cavity and the whole body. Current caries prevention measures such as fluoride treatment, antimicrobial agents, and traditional Chinese herbal, have limitations to some extent. Here we design and synthesize a novel peptide based on the amelogenin, and assess its ability to promote the remineralization of initial enamel caries lesions. We used enamel blocks to form initial lesions, and then subjected to 12-day pH cycling in the presence of peptide, NaF and HEPES buffer. Enamel treated with peptide or NaF had shallower, narrower lesions, thicker remineralized surfaces and less mineral loss than enamel treated with HEPES. This peptide can promote the remineralization of initial enamel caries and inhibit the progress of caries. It is a promising anti-caries agent with various research prospects and practical application value.

  18. Remineralization of particulate organic carbon in an ocean oxygen minimum zone

    NASA Astrophysics Data System (ADS)

    Cavan, E. L.; Trimmer, M.; Shelley, F.; Sanders, R.

    2017-03-01

    Biological oceanic processes, principally the surface production, sinking and interior remineralization of organic particles, keep atmospheric CO2 lower than if the ocean was abiotic. The remineralization length scale (RLS, the vertical distance over which organic particle flux declines by 63%, affected by particle respiration, fragmentation and sinking rates) controls the size of this effect and is anomalously high in oxygen minimum zones (OMZ). Here we show in the Eastern Tropical North Pacific OMZ 70% of POC remineralization is due to microbial respiration, indicating that the high RLS is the result of lower particle fragmentation by zooplankton, likely due to the almost complete absence of zooplankton particle interactions in OMZ waters. Hence, the sensitivity of zooplankton to ocean oxygen concentrations can have direct implications for atmospheric carbon sequestration. Future expansion of OMZs is likely to increase biological ocean carbon storage and act as a negative feedback on climate change.

  19. In vitro evaluation of the efficacy of laser fluorescence (DIAGNOdent) to detect demineralization and remineralization of smooth enamel lesions

    PubMed Central

    Bahrololoomi, Zahra; Musavi, Seyed Ahmad; Kabudan, Mona

    2013-01-01

    Objective: Early detection of smooth surface lesions is important for appropriate management and monitoring of dental caries. The purpose of this in vitro study was to evaluate the efficacy of laser fluorescence to detect demineralization and remineralization of smooth enamel surfaces. Materials and Methods: In this in vitro study, 132 enamel blocks of semi-impacted human third molars were obtained; artificial caries lesions were induced and they were submitted to the pH-cycling process to create remineralization. Superficial microhardness (SMH) and laser fluorescence (LF) analysis were performed at baseline, after demineralization, and remineralization processes. The data were analyzed by Statistical Package for Social Sciences (SPSS)-16 using analysis of variance (ANOVA), Paired samples t-test, and Pearson's correlation test. Results: There was a significant difference between SMH values at baseline, after demineralization and after remineralization. Also, a statistically significant difference was observed between LF values in these three stages. The LF values increased after demineralization and then decreased after remineralization, and the SMH values decreased after demineralization and increased after remineralization. There was an inverse relationship between SMH and LF only at baseline and after demineralization, but not after remineralization. Conclusion: The results showed that LF is an appropriate method for detection of demineralization in an in vitro condition in smooth enamel lesions, but it was not so efficient in the detection of remineralization. PMID:23956542

  20. Changes in Stiffness of Resin-infiltrated Demineralized Dentin after Remineralization with a Bottom-up Biomimetic Approach

    PubMed Central

    Gu, Li-sha; Huffman, Bradford P.; Arola, Dwayne D.; Kim, Young Kyung; Mai, Sui; Elsalanty, Mohammed E.; Pashley, David H.; Tay, Franklin R.

    2009-01-01

    This study examined changes in elastic modulus, mineral density and ultrastructure of resin-infiltrated dentin after biomimetic remineralization. Sixty demineralized dentin beams were infiltrated with Clearfil Tri-S Bond, One-Step or Prime&Bond NT. They were immersed in simulated body fluid (SBF) for one week to maximize water sorption before determining the baseline elastic moduli. For each adhesive (N=20), half of the beams remained immersed in SBF (control). The rest were immersed in a biomimetic remineralization medium. The elastic moduli were measured weekly for 15 additional weeks. Representative remineralized specimens were evaluated with X-ray microtomography and transmission electron microscopy (TEM). The elastic moduli of control resin-infiltrated dentin remained consistently low, while those immersed in the biomimetic remineralization medium increased by 55–118% after 4-months. X-ray microtomography of the remineralized specimens revealed decreases in mineral density from the beam surface to the beam core that was indicative of external mineral aggregation and internal mineral deposition. Interfibrillar and intrafibrillar remineralization of resin-sparse intertubular dentin were seen under TEM together with remineralized peritubular dentin. Biomimetic remineralization occurs by diffusion of nanoprecursors and biomimetic analogs in completely demineralized resin-infiltrated dentin and proceeds without the contribution of materials released from a mineralized dentin base. PMID:19887126

  1. In vitro evaluation of remineralization efficacy of different calcium- and fluoride-based delivery systems on artificially demineralized enamel surface

    PubMed Central

    Gangrade, Aparajita; Gade, Vandana; Patil, Sanjay; Gade, Jaykumar; Chandhok, Deepika; Thakur, Deepa

    2016-01-01

    Background: Caries is the most common dental disease facing the world population. Caries can be prevented by remineralizing early enamel lesions. Aim: To evaluate remineralization efficacy of stannous fluoride (SnF2), casein phosphopeptide-amorphous calcium phosphate with fluoride (CPP-ACPF) and calcium sucrose phosphate (CaSP). Materials and Methods: Fifty enamel samples were taken; they were divided into five groups (n = 10). Demineralization was carried out with Groups A, B, C, and E. Remineralization was carried out with Groups A, B, and C for 7 days using SnF2, CPP-ACPF, and CaSP, respectively. In Group D, no surface treatment was carried out, to mark as positive control whereas Group E was kept as negative control with only surface demineralization of enamel. Enamel microhardness was tested using Vickers's microhardness tester after 7 day remineralization regime. Statistical Analysis: One-way analysis of variance and post hoc Tukey tests were performed. Results: The mean microhardness values in descending order: Positive control > SnF2> CaSP > CPP-ACPF > negative control. Conclusion: All remineralizing agents showed improved surface remineralization. However, complete remineralization did not occur within 7 days. SnF2 showed the highest potential for remineralization followed by CaSP and CPP-ACPF. PMID:27563180

  2. Monitoring of enamel lesion remineralization by optical coherence tomography: an alternative approach towards signal analysis

    NASA Astrophysics Data System (ADS)

    Sadr, Alireza; Mandurah, Mona; Nakashima, Syozi; Shimada, Yasushi; Kitasako, Yuichi; Tagami, Junji; Sumi, Yasunori

    Early detection, monitoring and remineralization repair of enamel lesions are top research priorities in the modern dentistry focusing on minimal intervention concept for caries management. We investigate the use of swept-source optical coherence tomography system (SS-OCT) without polarization-sensing at 1319 nm wavelength developed for clinical dentistry (Dental OCT System Prototype 2, Panasonic Healthcare Co., Ltd., Japan) in quantitative assessment of artificial enamel lesions and their remineralization. Bovine enamel blocks were subjected to demineralization to create subsurface lesions approximately 130 μm in depth over 2 weeks, and subjected to remineralization in solution containing bioavailable calcium and 1ppm fluoride at pH 6.5 for 2 weeks. Cross-sectional images of sound, demineralized and remineralized specimens were captured under hydrated conditions by the OCT. Finally, the specimens were cut into sections for nanoindentation to measure hardness through the lesion under 2mN load. Reflectivity had increased with demineralization. OCT images of lesions showed a boundary closely suggesting the lesion depth that gradually progressed with demineralization time. After remineralization, the boundary depth gradually decreased and nanoindentation showed over 60% average hardness recovery rate. A significant negative correlation was found between the slope power-law regression as a measure of attenuation and overall nanohardness for a range of data covering sound, demineralized and remineralized areas. In conclusion, OCT could provide clear images of early enamel lesion extent and signal attenuation could indicate its severity and recovery. Clinical data of natural lesions obtained using Dental OCT and analyzed by this approach will also be presented. Study supported by GCOE IRCMSTBD and NCGG.

  3. Leucine-rich amelogenin peptide (LRAP) as a surface primer for biomimetic remineralization of superficial enamel defects: An in vitro study.

    PubMed

    Shafiei, Farhad; Hossein, Bagheri G; Farajollahi, Mohammad M; Fathollah, Moztarzadeh; Marjan, Behroozibakhsh; Tahereh, Jafarzadeh Kashi

    2015-01-01

    This study was carried out to obtain more information about the assembly of hydroxyapatite bundles formed in the presence of Leucine-Rich Amelogenin Peptide (LRAP) and to evaluate its effect on the remineralization of enamel defects through a biomimetic approach. One or 2 mg/mL LRAP solutions containing 2.5 mM of Ca(+2) and 1.5 mM phosphate were prepared (pH = 7.2) and stored at 37 °C for 24 h. The products of the reaction were studied using atomic force microscopy (AFM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED). Vickers surface microhardness recovery (SMR%) of acid-etched bovine enamel, with or without LRAP surface treatment, were calculated to evaluate the influence of peptide on the lesion remineralization. Distilled water and 1 or 2 mg/mL LRAP solution (pH = 7.2) were applied on the lesions and the specimens were incubated in mineralization solution (2.5mM Ca(+2) , 1.5mM PO4 (-3) , pH = 7.2) for 24 h. One-way ANOVA and Tukey's multi-comparison tests were used for statistical analysis. The pattern of enamel surface repair was studied using FE-SEM. AFM showed the formation of highly organized hierarchical structures, composed of hydroxyapatite (HA) crystals, similar to the dental enamel microstructure. ANOVA procedure showed significant effect of peptide treatment on the calculated SMR% (p < 0.001). Tukey's test revealed that peptide treated groups had significantly higher values of SMR%. In conclusion, LRAP is able to regulate the formation of HA and enhances the remineralization of acid-etched enamel as a surface treatment agent.

  4. Remineralization and repair of enamel surface by biomimetic Zn-carbonate hydroxyapatite containing toothpaste: a comparative in vivo study.

    PubMed

    Lelli, Marco; Putignano, Angelo; Marchetti, Marco; Foltran, Ismaela; Mangani, Francesco; Procaccini, Maurizio; Roveri, Norberto; Orsini, Giovanna

    2014-01-01

    Consumption of acidic foods and drinks and other factors that cause enamel wear are responsible for the daily enamel loss and degradation. Use of some toothpastes that have been showed to possess different properties of remineralisation and/or repair of the enamel surface may help to protect tooth enamel. The aim of this study was to evaluate whether the use of toothpaste containing Zn-carbonate hydroxyapatite (CHA) nanostructured microcrystals may exert remineralization/repair effects of the enamel surface. Two groups of patients, aged between 18 and 75 years, used a Zn-CHA nanocrystals-based toothpaste (experimental group) and a potassium nitrate/sodium fluoride toothpaste (active control group) for 8 weeks. At the end of this period, extractions were performed in five subjects per study group. Negative controls consisted of two subjects treated with non-specified fluoride toothpaste. Teeth were processed for morphological and chemical-physic superficial characterizations by means of Scanning Electronic Microscopy with Elementary analysis, X-Ray Diffraction analysis and Infrared analysis. In this study, the use of a Zn-CHA nanocrystals toothpaste led to a remineralization/repair of the enamel surface, by deposition of a hydroxyapatite-rich coating. On the other hand, the use of both a nitrate potassium/sodium fluoride and non-specified fluoride toothpastes did not appreciably change the enamel surface. In conclusion, this study demonstrates that the toothpaste containing Zn-CHA nanostructured microcrystals, differently from nitrate potassium/sodium fluoride and non-specified fluoride toothpastes, may promote enamel superficial repair by means of the formation of a protective biomimetic CHA coating.

  5. Controlled-protein dietary regimens for Parkinson's disease.

    PubMed

    Cereda, Emanuele; Barichella, Michela; Pezzoli, Gianni

    2010-02-01

    Continuous levodopa replacement still is the most efficacious treatment for patients with Parkinson's disease. Unfortunately, the neutral aromatic amino acids contained in dietary proteins may compete with this drug for intestinal absorption and transport across the blood-brain barrier, thus limiting its efficacy and being responsible for the occurrence of motor fluctuations. Current guidelines recommend low-protein dietary regimens with protein redistribution, as shifting protein intake to the evening has proved to ameliorate the response to levodopa. However, adherence to this dietary regimen does not seem to be satisfactory and response is variable. Recent studies have shown that low-protein products designed for chronic renal failure patients are safe, tasty, well-tolerated and useful in improving both adherence to low-protein dietary regimens and levodopa-related motor fluctuations. However, there still is the need to define the selection criteria for the patients who may benefit the most from adherence to this regimen.

  6. Early spring mesopelagic carbon remineralization and transfer efficiency in the naturally iron-fertilized Kerguelen area

    NASA Astrophysics Data System (ADS)

    Jacquet, S. H. M.; Dehairs, F.; Lefèvre, D.; Cavagna, A. J.; Planchon, F.; Christaki, U.; Monin, L.; André, L.; Closset, I.; Cardinal, D.

    2015-03-01

    We report on the zonal variability of mesopelagic particulate organic carbon remineralization and deep carbon transfer potential during the Kerguelen Ocean and Plateau compared Study 2 expedition (KEOPS 2; October-November 2011) in an area of the polar front supporting recurrent massive blooms from natural Fe fertilization. Mesopelagic carbon remineralization (MR) was assessed using the excess, non-lithogenic particulate barium (Baxs) inventories in mesopelagic waters and compared with bacterial production (BP), surface primary production (PP) and export production (EP). Results for this early season study are compared with the results obtained during a previous study (2005; KEOPS 1) for the same area at a later stage of the phytoplankton bloom. Our results reveal the patchiness of the seasonal advancement and of the establishment of remineralization processes between the plateau (A3) and polar front sites during KEOPS 2. For the Kerguelen plateau (A3 site) we observe a similar functioning of the mesopelagic ecosystem during both seasons (spring and summer), with low and rather stable remineralization fluxes in the mesopelagic column (150-400 m). The shallow water column (~500 m), the lateral advection, the zooplankton grazing pressure and the pulsed nature of the particulate organic carbon (POC) transfer at A3 seem to drive the extent of MR processes on the plateau. For deeper stations (>2000 m) located on the margin, inside a polar front meander, as well as in the vicinity of the polar front, east of Kerguelen, remineralization in the upper 400 m in general represents a larger part of surface carbon export. However, when considering the upper 800 m, in some cases, the entire flux of exported carbon is remineralized. In the polar front meander, where successive stations form a time series, two successive events of particle transfer were evidenced by remineralization rates: a first mesopelagic and deep transfer from a past bloom before the cruise, and a second

  7. Microstructure and nanomechanical properties of enamel remineralized with asparagine-serine-serine peptide.

    PubMed

    Chung, Hsiu-Ying; Li, Cheng Che

    2013-03-01

    A highly biocompatible peptide, triplet repeats of asparagine-serine-serine (3 NSS) was designed to regulate mineral deposition from aqueous ions in saliva for the reconstruction of enamel lesions. Healthy human enamel was sectioned and acid demineralized to create lesions, then exposed to the 3 NSS peptide solution, and finally immersed in artificial saliva for 24h. The surface morphology and roughness were examined using scanning electron microscopy (SEM) and atomic force microscopy (AFM), respectively. X-ray diffraction (XRD) was used to identify the phases and crystallinity of the deposited minerals observed on the enamel surface. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was used to quantitatively analyze the mineral variation by calculating the relative integrated-area of characteristic bands. Nanohardness and elastic modulus measured by nanoindentation at various treatment stages were utilized to evaluate the degree of recovery. Biomimetic effects were accessed according to the degree of nanohardness recovery and the amount of hydroxyapatite deposition. The charged segments in the 3 NSS peptide greatly attracted aqueous ions from artificial saliva to form hydroxyapatite crystals to fill enamel caries, in particular the interrod areas, resulting in a slight reduction in overall surface roughness. Additionally, the deposited hydroxyapatites were of a small crystalline size in the presence of the 3 NSS peptide, which effectively restrained the plastic deformations and thus resulted in greater improvements in nanohardness and elastic modulus. The degree of nanohardness recovery was 5 times greater for remineralized enamel samples treated with the 3 NSS peptide compared to samples without peptide treatment.

  8. Ions-modified nanoparticles affect functional remineralization and energy dissipation through the resin-dentin interface.

    PubMed

    Toledano, Manuel; Osorio, Raquel; Osorio, Estrella; Medina-Castillo, Antonio Luis; Toledano-Osorio, Manuel; Aguilera, Fátima S

    2017-04-01

    The aim of this study was to evaluate changes in the mechanical and chemical behavior, and bonding ability at dentin interfaces infiltrated with polymeric nanoparticlesstandard deviations and modes of failure are (NPs) prior to resin application. Dentin surfaces were treated with 37% phosphoric acid followed by application of an ethanol suspension of NPs, Zn-NPs or Ca-NPs followed by the application of an adhesive, Single Bond (SB). Bonded interfaces were stored for 24h, submitted to microtensile bond strength test, and evaluated by scanning electron microscopy. After 24h and 21 d of storage, the whole resin-dentin interface adhesive was evaluated using a Nano-DMA. Complex modulus, storage modulus and tan delta (δ) were assessed. AFM imaging and Raman analysis were performed. Bond strength was not affected by NPs infiltration. After 21 d of storage, tan δ generally decreased at Zn-NPs/resin-dentin interface, and augmented when Ca-NPs or non-doped NPs were used. When both Zn-NPs and Ca-NPs were employed, the storage modulus and complex modulus decreased, though both moduli increased at the adhesive and at peritubular dentin after Zn-NPs infiltration. The phosphate and the carbonate peaks, and carbonate substitution, augmented more at interfaces promoted with Ca-NPs than with Zn-NPs after 21 d of storage, but crystallinity did not differ at created interfaces with both ions-doped NPs. Crosslinking of collagen and the secondary structure of collagen improved with Zn-NPs resin-dentin infiltration. Ca-NPs-resin dentin infiltration produced a favorable dissipation of energy with minimal stress concentration trough the crystalline remineralized resin-dentin interface, causing minor damage at this structure.

  9. A simple model for the effect of flouride ions on remineralization of partly demineralized tooth enamel

    NASA Astrophysics Data System (ADS)

    Christoffersen, J.; Christoffersen, M. R.; Arends, J.

    1984-06-01

    A model is presented for remineralization of partly demineralized tooth enamel, taking the effect of the presence of fluoride ions into account. The model predicts that, in the absence of precipitation of other phases than calcium hydroxyapatite (HAP) and fluroridized HAP, which are assumed to model enamel, there exists a maximum value of the fluoride concentration gradient, above which lesions cannot be successfully repaired.

  10. Experimental investigation of demineralization and remineralization of human teeth using infrared photothermal radiometry and modulated luminescence

    NASA Astrophysics Data System (ADS)

    Jeon, Raymond J.; Hellen, Adam; Matvienko, Anna; Mandelis, Andreas; Abrams, Stephen H.; Amaechi, Bennett T.

    2008-02-01

    Photothermal radiometry (PTR) and modulated luminescence (LUM) were applied to detect and monitor the demineralization of root and enamel surfaces of human teeth to produce caries lesions and the subsequent remineralization of the produced lesions. The experimental set-up consisted of a semiconductor laser (659 nm, 120 mW), a mercury-cadmium-telluride IR detector for PTR, a photodiode for LUM, and two lock-in amplifiers. A lesion was created on a 1-mm × 4-mm rectangular window, spanning root to enamel surface, using an artificial caries lesion gel to demineralize the tooth surface and create small carious lesions. The samples were subsequently immersed in a remineralization solution. Each sample was examined with PTR/LUM on root and enamel before and after treatment at times from 1 to 10 days of demineralization and 2 to 10 days of remineralization. PTR/LUM signals showed gradual and consistent changes with treatment time. At the completion of the experiments, transverse micro-radiography (TMR) analysis was performed to correlate the PTR/LUM signals to depth of the carious lesions and mineral losses. In this study, TMR showed good correlation with PTR/LUM. It was also found that treatment duration did not correlate well to any technique, PTR/LUM, or TMR, which is indicative of significant variations in demineralization - remineralization rates among different teeth.

  11. Ensuring compliance with drug regimens.

    PubMed

    Clarence, M

    This article explores the difficulties patients encounter in complying with prescribed drug regimens, and describes some of the compliance aids which are commonly available. A sensitive understanding of patients' individual difficulties by health care staff is an essential precursor to successful compliance behaviour.

  12. Remineralization of organic carbon in eastern Canadian continental margin sediments

    NASA Astrophysics Data System (ADS)

    Silverberg, Norman; Sundby, Bjørn; Mucci, Alfonso; Zhong, Shaojun; Arakaki, Takeshi; Hall, Per; Landén, Angela; Tengberg, Anders

    2000-04-01

    .6 - 4.2 mmol/m 2/d) was estimated as the sum of the sediment oxygen and nitrate uptake rates. The contribution of other electron-acceptors to the mineralization of organic carbon is assumed to be accounted for by the oxidation of most of their reduced by-products by O 2 and NO 3-. The return fluxes of dissolved inorganic carbon (∑CO 2 efflux corrected for carbonate dissolution) were generally comparable to the carbon oxidation rates. A detailed carbon budget was established at one of the sampled stations for which a complete set of measurements is available. The vertical flux of total particulate carbon through the water column (measured with a sediment trap at 150 m depth) accounts for approximately 9% of the annual primary production (PP). In the sediment, about 6% of the PP is remineralized and total carbon equivalent to 4.5% PP is buried. The self-consistency of the flux data at this station is used to justify similar budget calculations at the other stations where a limited data set was gathered. Sequestration of organic carbon via burial with the accumulating sediments (on average 0.5 mol/m 2/yr) is partially offset by the release of CO 2 associated with carbonate precipitation and burial (about 0.2 mol/m 2/yr).

  13. Nanotribological and Nanomechanical Properties Changes of Tooth After Bleaching and Remineralization in Wet Environment

    NASA Astrophysics Data System (ADS)

    Yu, Dandan; Gao, Shanshan; Min, Jie; Zhang, Qianqian; Gao, Shuai; Yu, Haiyang

    2015-12-01

    Teeth bleaching cases had increased with people's desire for oral aesthetic; however, bleached teeth would still undertake chewing actions and remineralizing process in saliva. Nanotribological and nanomechanical properties are proper displays for dental performance of bleached teeth. The purpose of the research was to reveal the effect of bleaching and remineralization on the nanotribological and nanomechanical properties of teeth in wet environment. The specimens were divided into four groups according to the bleaching products used: 12 % hydrogen peroxide (HP) (12HP group); 15 % carbamide peroxide (CP) (15CP group); 35 % CP (35CP group); and artificial saliva (control group). The nanotribological and nanomechanical property changes of tooth enamel after bleaching and remineralization were evaluated respectively by nanoscratch and nanoindentation tests in wet environment, imitating the wet oral environment. The morphology changes were evaluated by statistical parametric mapping (SPM) and scanning electron microscopy (SEM). After bleaching, 12HP group and 15CP group showed increased scratch depth with more pile ups on the scratch edges, decreased nanohardness, and corroded surface appearance. While the 35CP group showed an increase in nanoscratch depth, no change in nanohardness and surface appearance was observed. The control group showed no change in these measurements. After remineralization, the three bleaching groups showed decreased nanoscratch depth and no change of nanohardness compared with the bleached teeth. And the control group showed no changes in nanotribological and nanomechanical properties. The nanotribological and nanomechanical properties of the 12HP group and 15CP group were affected by bleaching, but the nanotribological properties recovered partly and the nanomechanical properties got no change after 1 week of remineralization. As for the 35CP group, the nanotribological properties were influenced and the nanomechanical properties were not

  14. Nanotribological and Nanomechanical Properties Changes of Tooth After Bleaching and Remineralization in Wet Environment.

    PubMed

    Yu, Dandan; Gao, Shanshan; Min, Jie; Zhang, Qianqian; Gao, Shuai; Yu, Haiyang

    2015-12-01

    Teeth bleaching cases had increased with people's desire for oral aesthetic; however, bleached teeth would still undertake chewing actions and remineralizing process in saliva. Nanotribological and nanomechanical properties are proper displays for dental performance of bleached teeth. The purpose of the research was to reveal the effect of bleaching and remineralization on the nanotribological and nanomechanical properties of teeth in wet environment. The specimens were divided into four groups according to the bleaching products used: 12 % hydrogen peroxide (HP) (12HP group); 15 % carbamide peroxide (CP) (15CP group); 35 % CP (35CP group); and artificial saliva (control group). The nanotribological and nanomechanical property changes of tooth enamel after bleaching and remineralization were evaluated respectively by nanoscratch and nanoindentation tests in wet environment, imitating the wet oral environment. The morphology changes were evaluated by statistical parametric mapping (SPM) and scanning electron microscopy (SEM). After bleaching, 12HP group and 15CP group showed increased scratch depth with more pile ups on the scratch edges, decreased nanohardness, and corroded surface appearance. While the 35CP group showed an increase in nanoscratch depth, no change in nanohardness and surface appearance was observed. The control group showed no change in these measurements. After remineralization, the three bleaching groups showed decreased nanoscratch depth and no change of nanohardness compared with the bleached teeth. And the control group showed no changes in nanotribological and nanomechanical properties. The nanotribological and nanomechanical properties of the 12HP group and 15CP group were affected by bleaching, but the nanotribological properties recovered partly and the nanomechanical properties got no change after 1 week of remineralization. As for the 35CP group, the nanotribological properties were influenced and the nanomechanical properties were

  15. Regional variability in particulate organic matter remineralization depths: an optimization and sensitivity study using a fast Earth system model

    NASA Astrophysics Data System (ADS)

    Wilson, Jamie; Barker, Stephen; Ridgwell, Andy

    2015-04-01

    Nutrient distributions and atmospheric CO2 concentrations are sensitive to changes in the global average depth of particulate organic matter (POM) remineralization in models. Model optimization studies have used this sensitivity to find global mean remineralization depths that result in the statistically best fit to tracer observations such as phosphate (PO4). However, recent global syntheses of sediment trap data have started to suggest the existence of significant spatial variability in the depth of POM remineralization. A number of hypothetical mechanisms have been proposed to explain this variability invoking a wide range of feedbacks on atmospheric CO2. Progress has been hindered by the relatively low sampling density of sediment trap data. In response to this, we explore whether there is an optimal set of regionally variable remineralization depths in an Earth system model that best fits observed PO4 fields and how robust these solutions are. We develop a new computationally fast phosphorous-only version of the Earth system model GENIE using a transport matrix to represent steady-state circulation. The ocean is divided into 15 biogeochemical biomes within which the remineralization depth is an independent parameter. Latin hypercube sampling is used to produce an ensemble of runs that efficiently sample across the range of potential combinations of remineralization depths, producing probability distributions for each region. Despite sensitivity to the global remineralization depth, we find that PO4 is actually relatively insensitive to regional changes in remineralization. An optimal combination of remineralization depths in the Atlantic is found that predicts deeper remineralization in the low latitudes and shallower at high latitudes, matching sediment trap observations. Shallow remineralization is also predicted in the North Pacific. However, remineralization depths in the Southern Ocean, South and Equatorial Pacific, and Indian Ocean cannot be successfully

  16. Effects of immersion in solution of an experimental toothpaste containing S-PRG filler on like-remineralizing ability of etched enamel.

    PubMed

    Iijima, Masahiro; Ito, Shuichi; Nakagaki, Susumu; Kohda, Naohisa; Muguruma, Takeshi; Saito, Takashi; Mizoguchi, Itaru

    2014-01-01

    This study investigated the like-remineralizing ability of experimental toothpaste containing surface reaction-type pre-reacted glassionomer (S-PRG) filler on etched enamel. Human enamel blocks were etched with 35% phosphoric acid and immersed in 5-mL distilled water, fourfold diluted solution of NaF-containing toothpaste, or S-PRG filler-containing experimental toothpaste. Nanoindentation testing was carried out during immersion and the enamel surfaces were observed by scanning electron microscopy. Elemental analysis of the ions in each solution was performed using inductively coupled plasma atomic emission spectroscopy and fluoride electrode. After 1 month of immersion, the hardness and elastic modulus of the specimen immersed in S-PRG filler-containing toothpaste showed significantly greater values than those of the specimen immersed in NaF-containing toothpaste. Considerable amounts of Al, B, Na, Si, Sr, F ions were detected in the solution of S-PRG filler-containing toothpaste. Experimental S-PRG filler-containing toothpaste may enhance the like-remineralizing ability of etched enamel surfaces due to its ion-releasing ability.

  17. Atomic force microscopic comparison of remineralization with casein-phosphopeptide amorphous calcium phosphate paste, acidulated phosphate fluoride gel and iron supplement in primary and permanent teeth: An in-vitro study

    PubMed Central

    Agrawal, Nikita; Shashikiran, N. D.; Singla, Shilpy; Ravi, K. S.; Kulkarni, Vinaya Kumar

    2014-01-01

    Context: Demineralization of tooth by erosion is caused by frequent contact between the tooth surface and acids present in soft drinks. Aim: The present study objective was to evaluate the remineralization potential of casein-phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste, 1.23% acidulated phosphate fluoride (APF) gel and iron supplement on dental erosion by soft drinks in human primary and permanent enamel using atomic force microscopy (AFM). Materials and Methods: Specimens were made from extracted 15 primary and 15 permanent teeth which were randomly divided into three treatment groups: CPP-ACP paste, APF gel and iron supplement. AFM was used for baseline readings followed by demineralization and remineralization cycle. Results and Statistics: Almost all group of samples showed remineralization that is a reduction in surface roughness which was higher with CPP-ACP paste. Statistical analysis was performed using by one-way ANOVA and Mann-Whitney U-test with P < 0.05. Conclusions: It can be concluded that the application of CPP-ACP paste is effective on preventing dental erosion from soft drinks. PMID:24808700

  18. Remineralization of human natural caries and artificial caries-like lesions with an experimental whisker-reinforced ART-composite

    PubMed Central

    Yang, Bin; Flaim, Glenn; Dickens, Sabine H.

    2011-01-01

    To compare the remineralization of human natural caries and artificial caries-like dentin lesions from a novel whisker-reinforced experimental composite resin to a resin-modified glass ionomer cement (RM-GIC) as control. Ten molars with moderate natural dentin caries were prepared (N). Artificial caries-like dentin lesions were prepared in occlusal dentin of ten caries-free molars and demineralized at pH=4.3 for 48 h (A). The cavities were restored with ART-composite or RM-GIC. All restored teeth were sliced into 120-μm sections. Transverse microradiography combined with digital image analysis was performed to analyze the change in mineral density at the same position of the specimens before, after 4 weeks and 8 weeks remineralization/demineralization treatment. The mean percent remineralization ± standard deviation after 4 weeks and 8 weeks are: N: ART-composite: 27±9, 46±14; RM-GIC: 18±6, 36±11; A: ART-composite: 48±9, 66±11; RM-GIC: 50±13, 62±11. For the remineralization of natural caries, there was a significant difference between ART-composite and RM-GIC (p<0.05). For both restoratives there were significant differences between remineralization of natural and artificial caries (p<0.001). ART-composite and RM-GIC remineralized natural and artificial caries differently most likely due to differences in microstructure and composition of caries dentin. PMID:21232637

  19. Sugar Alcohols, Caries Incidence, and Remineralization of Caries Lesions: A Literature Review

    PubMed Central

    Mäkinen, Kauko K.

    2010-01-01

    Remineralization of minor enamel defects is a normal physiological process that is well known to clinicians and researchers in dentistry and oral biology. This process can be facilitated by various dietary and oral hygiene procedures and may also concern dentin caries lesions. Dental caries is reversible if detected and treated sufficiently early. Habitual use of xylitol, a sugar alcohol of the pentitol type, can be associated with significant reduction in caries incidence and with tooth remineralization. Other dietary polyols that can remarkably lower the incidence of caries include erythritol which is a tetritol-type alditol. Based on known molecular parameters of simple dietary alditols, it is conceivable to predict that their efficacy in caries prevention will follow the homologous series, that is, that the number of OH-groups present in the alditol molecule will determine the efficacy as follows: erythritol ≥ xylitol > sorbitol. The possible difference between erythritol and xylitol must be confirmed in future clinical trials. PMID:20339492

  20. In vivo remineralization by a monofluorophosphate dentifrice as determined with a thin-section sandwich method.

    PubMed

    Mellberg, J R; Castrovince, L A; Rotsides, I D

    1986-08-01

    Artificial caries lesions were formed in thin sections of subsurface enamel sandwiched between protective sheets of plastic. Six lesions were placed into the buccal surfaces of lower partial dentures of seven subjects, covered with a stainless steel mesh to provide a plaque cover, and brushed with either a sodium monofluorophosphate or placebo dentifrice for four weeks, by means of a double-blind random cross-over design. Analysis of the lesions by quantitative microradiography revealed that significant remineralization (21%) occurred in the monofluorophosphate group and significant further demineralization (27%) in the placebo group. The difference between the active and placebo treatments was significant (p = 0.02), showing that the monofluorophosphate was effective not only in preventing lesion progression but also in promoting mineral deposition. The simultaneous presence of remineralized lesions and lesions with increased demineralization showed the non-uniformity of conditions within a mouth.

  1. Surficial bioturbation and rapid benthic remineralization in the Cape Hatteras shelf/slope region. Final report

    SciTech Connect

    Robert C. Aller; Josephine Y. Aller; C. Lee; J. Kirk Cochran

    1999-03-17

    This is a final report for the DOE of grant DE-FG02-92ER61464 ''Surficial bioturbation and rapid benthic remineralization in the Cape Hatteras shelf slope region''. Over the past 6 years we have participated in a multidisciplinary field study called the Ocean margins Program (OMP) to examine the importance of continental margins in the global carbon cycle. Specifically, we have focused on the southern portion of the Mid-Atlantic Bight between Cape Hatteras and Chesapeake Bay where a large flux of freshwater and organic carbon enters the North Atlantic Ocean. Additionally, during the first stage of this project, we developed the use of CM-a distributions in sediments as a quantitative indicator of benthic C flux and remineralization rates. The primary objective of our research group has been to understand mechanisms and quantify biogeochemical processes in the seabed that affect cycling, flux, and storage of carbon on the ocean margin of the Mid-Atlantic Bight.

  2. Triclosan-loaded poly(amido amine) dendrimer for simultaneous treatment and remineralization of human dentine.

    PubMed

    Zhou, Yan; Yang, Jiaojiao; Lin, Zaifu; Li, Jiyao; Liang, Kunneng; Yuan, He; Li, Sheyu; Li, Jianshu

    2014-03-01

    In order to treat dental caries of damaged dentine, triclosan-loaded carboxyl-terminated poly(amido amine) dendrimer (PAMAM-COOH) is prepared and characterized. While being incubated in artificial saliva, triclosan-loaded PAMAM-COOH formulation can induce in situ remineralization of hydroxyapatite (HA) on etched dentine, and the regenerated HA has a similar crystal structure with natural dentine. It can also release the encapsulated triclosan for a long period. The interesting drug release profiles are controlled by both dendrimer encapsulation capability and the mineralization degree, which are ideal to obtain multifunctional properties of long-term release of anti-bacterial drug for local treatment during the remineralization process. The triclosan-loaded G4-COOH provides a general strategy to cure dental caries and repair damaged dentine at the same time, which forms a potential restorative material for dental repair.

  3. Effect of Biomimetic Remineralization on the Dynamic Nanomechanical Properties of Dentin Hybrid Layers

    PubMed Central

    Ryou, H.; Niu, L.-N.; Dai, L.; Pucci, C.R.; Arola, D.D.; Pashley, D.H.; Tay, F.R.

    2011-01-01

    The mineral and organic phases of mineralized dentin contribute co-operatively to its strength and toughness. This study tested the null hypothesis that there is no difference in nano-dynamic mechanical behavior (complex modulus-E*; loss modulus-E′′; storage modulus-E′; in GPa) of dentin hybrid layers (baseline: E*, 3.86 ± 0.24; E′′, 0.23 ± 0.05; E′, 3.85 ± 0.24) created by an etch-and-rinse adhesive in the presence or absence of biomimetic remineralization after in vitro aging. Using scanning probe microscopy and nano-dynamic mechanical analysis, we demonstrated that biomimetic remineralization restored the nano-dynamic mechanical behavior of heavily remineralized, resin-sparse regions of dentin hybrid layers (E*, 19.73 ± 3.85; E′′, 8.75 ± 3.97; E′, 16.02 ± 2.58) to those of the mineralized dentin base (E*, 19.20 ± 2.42; E′′, 6.57 ± 1.96; E′, 17.39 ± 2.0) [p > 0.05]. Conversely, those resin-sparse, water-rich regions degraded in the absence of biomimetic remineralization, with significant decline [p < 0.05] in their complex and storage moduli (E*, 0.83 ± 0.35; E′′, 0.88 ± 0.24; E′, 0.62 ± 0.32). Intrafibrillar apatite deposition preserves the integrity of resin-sparse regions of hybrid layers by restoring their nanomechanical properties to those exhibited by mineralized dentin. PMID:21730254

  4. [Effect of sucrose-containing gum and fluoridated dentifrice on in situ remineralization of artificial caries].

    PubMed

    de Freitas, R R; de Oliveira, J A; Taga, E M; Buzalaf, M A

    2001-01-01

    The aim of this study was to evaluate the remineralization of incipient carious lesions in bovine enamel in situ. Artificial carious lesions were produced and fixed in removable lower appliances in the region of the lingual surfaces of first molars, in six volunteers with ages between 18 and 22 years, who were subjected to 3 distinct experimental periods of 1 week each. In the first period (control group), patients brushed their teeth with a non-fluoridated dentifrice 4 times a day (after meals), and, in the second period (group I), patients used a dentifrice containing 1,500 ppm of fluorine (in the form of MFP). In the third period (group II) volunteers brushed their teeth with non-fluoridated dentifrice and used chewing gum containing 60% of sucrose during 20 minutes, 4 times a day (after meals). Before and after each treatment, the specimens underwent Vicker's hardness test (200 g of load), and the remineralization percentage (alpha) was calculated. The control group showed 2.78% of demineralization, and groups I and II showed 3.36 and 5.21% of remineralization, respectively. Statistical analysis (with Kruskal-Wallis and Miller's tests) showed significant difference (p < 0.05) between the control and experimental groups (I and II). Group II showed greater alpha than group I, but this difference was not significant. These results suggest that the use of sucrose-containing chewing gum and fluoridated dentifrice has a considerable effect on the remineralization of incipient carious lesions and may be a valuable alternative for their prevention.

  5. Remineralizing potential, antiplaque and antigingivitis effects of xylitol and sorbitol sweetened chewing gum.

    PubMed

    Steinberg, L M; Odusola, F; Mandel, I D

    1992-01-01

    The objective of this study was to investigate the effects of xylitol and sorbitol sweetened chewing gums on plaque accumulation, gingival inflammation and remineralizing potential of plaque following six weeks of use. Twenty-eight consenting individuals were randomly assigned to each of three phases (six weeks in duration) consisting of chewing xylitol gum, chewing sorbitol gum and a non-chewing phase. Subjects chewed one stick after every meal and at two other times for a total of five sticks per day. At the completion of each treatment phase, plaque and gingival indexes were performed and plaque was later collected. Calcium concentration in plaque was determined by atomic absorption spectophotometry. Reductions in plaque indexes were significant for both xylitol gum (p < 0.001) and sorbitol gum (p < 0.05) when compared to the no chewing period. The gingival indexes reflected a decrement in gingival inflammation with both xylitol and sorbitol, though only sorbitol values were statistically significant (p < 0.05). Chewing xylitol and sorbitol gums reduced plaque accumulation and gingival inflammation. In addition, both gums enhanced the remineralization potential of plaque. Xylitol gum showed a superior effect with respect to remineralization potential and plaque reduction. Sorbitol gum had a superior effect on gingival health but not significantly so.

  6. Biomimetic remineralization as a progressive dehydration mechanism of collagen matrices – implications in the aging of resin-dentin bonds

    PubMed Central

    Kim, Young Kyung; Mai, Sui; Mazzoni, Annalisa; Liu, Yan; Tezvergil-Mutluay, Arzu; Takahashi, Kei; Zhang, Kai; Pashley, David H.; Tay, Franklin R.

    2010-01-01

    Biomineralization is a dehydration process in which water from the intrafibrillar compartments of collagen fibrils are progressively replaced by apatites. As water is an important element that precipitates the lack of durability of resin-dentin bonds, this study examined the use of a biomimetic remineralization strategy as a progressive dehydration mechanism for preserving joint integrity and maintaining adhesive strength after aging. Human dentin surfaces were bonded with dentin adhesives, restored with resin composites and sectioned into sticks containing the adhesive joint. Experimental specimens were aged in a biomimetic analog-containing remineralizing medium and control specimens in simulated body fluid for up to 12 months. Specimens retrieved from the designated periods were examined by transmission electron microscopy for manifestation of water-rich regions using a silver tracer and for collagen degradation within the adhesive joints. Tensile testing was performed to determine the potential loss of bond integrity after aging. Control specimens exhibited severe collagen degradation within the adhesive joint after aging. Remineralized specimens exhibited progressive dehydration as manifested by silver tracer reduction and partial remineralization of water-filled micro-channels within the adhesive joint, as well as intrafibrillar remineralization of collagen fibrils that were demineralized initially as part of the bonding procedure. Biomimetic remineralization as a progressive dehydration mechanism of water-rich, resin-sparse collagen matrices enables those adhesive joints to resist degradation over the 12-month aging period, as verified by the conservation of their tensile bond strengths. The ability of the proof-of-concept biomimetic remineralization strategy to prevent bond degradation warrants further development of clinically-relevant delivery systems. PMID:20304110

  7. A Comparative Analysis of Caries Inhibitory Effect of Remineralizing Agents on Human Enamel Treated With Er:YAG Laser: An In-vitro Atomic Emission Spectrometry Analysis

    PubMed Central

    Nair, Aswin Saseendran; Kumar, R Krishna; Ahameed, Syed Shaheed; Punnathara, Sairaj; Peter, Joby

    2016-01-01

    Introduction The tug of war to maintain tooth integrity is dependent on a ratio between demineralization and remineralization. Hence, demineralization should be retarded and remineralization should be enhanced to maintain a natural equilibrium in the oral cavity. Aim To compare in-vitro acid resistance of human enamel when using Casein Phosphopeptides Amorphous Calcium Phosphate (CPP-ACP) [GC Tooth mousse] cream, Casein Phosphopeptide Amorphous Calcium Fluoride Phosphate (CPP-ACFP) [GC Tooth mousse plus] cream, Er:YAG laser alone, combination of CPP-ACP with Er:YAG laser, CPP-ACFP with Er:YAG laser. Materials and Methods An in-vitro study was done on 100 specimens which were prepared from 50 human premolars to investigate the caries inhibitory effect of remineralizing agents and laser on enamel using an atomic emission spectrometry analysis. The enamel specimens were randomly allocated into 6 groups: Untreated (control); CPP-ACP (GC Tooth mousse); CPP-ACFP (GC Tooth mousse plus); Er:YAG laser treatment alone; CPP-ACP with Er:YAG laser; CPP-ACFP with Er: YAG laser. Then specimens were immersed individually in 5ml of acetate buffer solution (0.1mol/L, pH 4.5) and incubated at 37°C for 24 hours, to determine the acid resistance by analyzing the calcium release using atomic emission spectrometry. An ANOVA model was constructed (p-value 0.05), followed by post-hoc Tukey’s test for multiple pair wise comparisons of mean values. Results There was a significant difference among the various groups with respect to amount of calcium released (p<0.001). The lowest mean score of calcium release was observed for CPP-ACFP with Er:YAG laser followed by CPP-ACFP but the differences between these groups were statistically not significant (p>0.05). Similarly the differences between CPP-ACP with Er:YAG laser and CPP-ACP also were not significant (p>0.05). The highest mean score of calcium release was for Er:YAG laser and no significant statistical difference was noticed in

  8. Components of the Goeckerman regimen.

    PubMed

    Le Vine, M J; White, H A; Parrish, J A

    1979-08-01

    Although application of tar products and subsequent exposure to ultraviolet radiation (the Goeckerman regimen) has repeatedly been demonstrated to be effective therapy for psoriasis, the therapeutic role of each component has remained uncertain. Utilizing the bilateral comparison technique in 30 hospitalized patients with chronic stable plaque-type psoriasis vulgaris, we closely monitored the clinical responses to ultraviolet radiation (Westinghouse fluorescent FS40 bulbs, 290--400 nm) and a variety of tar preparations and lubricant vehicles in combination and separately. We found that: 1) 4 weeks of maximally-aggressive exposure to ultraviolet radiation alone will markedly improve, but not completely clear, psoriasis unless combined with a tar preparation or lubricating base; 2) 5% crude coal tar plus ultraviolet radiation offers no clear advantage or benefit over lubricating base plus ultraviolet radiation; and 3) none of the tar preparations tested offered any consistent advantage over any other preparation.

  9. Biological factors in dental caries enamel structure and the caries process in the dynamic process of demineralization and remineralization (part 2).

    PubMed

    Hicks, John; Garcia-Godoy, Franklin; Flaitz, Catherine

    2004-01-01

    Dental caries is a complex disease process that afflicts a large proportion of the world's population, regardless of gender, age and ethnicity, although it does tend to affect more indivduals with a low socioeconomic status to a greater extent. The physicochemical properties of the mineral comprising the tooth surface and subsurface modulate the development, arrestment and remineralization of dental caries. Post-eruption maturation of enamel surfaces and exposed root surfaces is important in order for more susceptible mineral phases to be modified by incorporation of soluble fluoride from the plaque into dental hydroxyapatite. The chemical reactions that occur during acidic conditions when tooth mineral dissolves (critical pH) are determined by the supersaturation of calcium and phosphate within plaque and saliva, as well as if fluoride is present.

  10. Effect of dentifrices on their remineralizing potential in artificial carious lesions: An in situ study

    PubMed Central

    Damle, Satyawan Gangaramji; Bector, Aditi; Damle, Dhanashree; Kaur, Simranjeet

    2016-01-01

    Background: The eventual sequel of dental caries is determined by the dynamic equilibrium between pathological factors which lead to demineralization and protective elements, which in turn leads to remineralization. Remineralization is the natural process for noncavitated demineralized lesions and relies on calcium and phosphate ions assisted by fluoride to rebuild a new surface on existing crystal remnants in subsurface lesions remaining after demineralization. Hence, the present study was designed to evaluate the efficacy of fluoride dentifrices in remineralizing artificial caries-like lesions in situ. Materials and Methods: A double-blind, randomized study with an initial washout period of 7 days was carried out for 3 weeks. Twenty volunteers were enrolled, who wore the intraoral cariogenicity test appliance having enamel slabs incorporated into them, for 3 weeks. 10 participants were instructed to use Group A dentifrice (fluoride) and the other 10 Group B dentifrice (nonfluoride) for brushing their teeth. The enamel slabs were analyzed by surface microhardness testing and scanning electron microscopy (SEM) at 3 intervals. Results: No significant differences was seen in the microhardness values recorded for Group A and Group B at baseline and after demineralization (P > 0.05); however Group B exhibited lesser microhardness compared to Group A, after intra-oral exposure (P < 0.05). In the SEM analysis, the Group A enamel surfaces had more regular and longer crystallites to those of the Group B. Conclusion: Fluoride dentifrices avert the decrease in enamel hardness and loss of minerals from the enamel surface to a large extent as compared to the nonfluoride dentifrices. PMID:26962320

  11. Organic Matter Remineralization Predominates Phosphorus Cycling in the Mid-Bay Sediments in the Chesapeake Bay

    SciTech Connect

    Sunendra, Joshi R.; Kukkadapu, Ravi K.; Burdige, David J.; Bowden, Mark E.; Sparks, Donald L.; Jaisi, Deb P.

    2015-05-19

    The Chesapeake Bay, the largest and most productive estuary in the US, suffers from varying degrees of water quality issues fueled by both point and non–point source nutrient sources. Restoration of the bay is complicated by the multitude of nutrient sources, their variable inputs and hydrological conditions, and complex interacting factors including climate forcing. These complexities not only restrict formulation of effective restoration plans but also open up debates on accountability issues with nutrient loading. A detailed understanding of sediment phosphorus (P) dynamics enables one to identify the exchange of dissolved constituents across the sediment- water interface and aid to better constrain mechanisms and processes controlling the coupling between the sediments and the overlying waters. Here we used phosphate oxygen isotope ratios (δ18Op) in concert with sediment chemistry, XRD, and Mössbauer spectroscopy on the sediment retrieved from an organic rich, sulfidic site in the meso-haline portion of the mid-bay to identify sources and pathway of sedimentary P cycling and to infer potential feedback effect on bottom water hypoxia and surface water eutrophication. Isotope data indicate that the regeneration of inorganic P from organic matter degradation (remineralization) is the predominant, if not sole, pathway for authigenic P precipitation in the mid-bay sediments. We interpret that the excess inorganic P generated by remineralization should have overwhelmed any bottom-water and/or pore-water P derived from other sources or biogeochemical processes and exceeded saturation with respect to authigenic P precipitation. It is the first research that identifies the predominance of remineralization pathway against remobilization (coupled Fe-P cycling) pathway in the Chesapeake Bay. Therefore, these results are expected to have significant implications for the current understanding of P cycling and benthic-pelagic coupling in the bay, particularly on the

  12. In vitro enamel remineralization by low-fluoride toothpaste with calcium citrate and sodium trimetaphosphate.

    PubMed

    Hirata, Edo; Danelon, Marcelle; Freire, Isabelle Rodrigues; Delbem, Alberto Carlos Botazzo

    2013-01-01

    The objective of this study was to evaluate in vitro the effect of a low fluoride toothpaste (450 µgF/g, NaF) combined with calcium citrate (Cacit) and sodium trimetaphosphate (TMP) on enamel remineralization. Bovine enamel blocks had the enamel surface polished sequentially to determine the surface hardness. After production of artificial carious lesions, the blocks selected by their surface hardness were submitted to remineralization pH cycling and daily treatment with dentifrice suspensions (diluted in deionized water or artificial saliva): placebo, 275, 450, 550 and 1,100 µgF/g and commercial dentifrice (positive control, 1,100 µgF/g). Finally, the surface and cross-section hardness was determined for calculating the change of surface hardness (%SH) and mineral content (%∆Z). Fluoride in enamel was also determined. The data from %SH, %∆Z and fluoride were subjected to two-way analysis of variance followed by Student-Newman-Keuls's test (p<0.05). The mineral gain (%SH and %∆Z) was higher for toothpastes diluted in saliva (p<0.05), except for the 450 µgF/g dentifrice with Cacit/TMP (p>0.05). The 450 Cacit/TMP toothpaste and the positive control showed similar results (p>0.05) when diluted in water. A dose-response was observed between fluoride concentration in toothpastes and fluoride present in enamel, regardless of dilution. It was concluded that it is possible to enhance the remineralization capacity of low F concentration toothpaste by of organic (Cacit) and inorganic (TMP) compounds with affinity to hydroxyapatite.

  13. Evaluation of the remineralization capacity of CPP-ACP containing fluoride varnish by different quantitative methods

    PubMed Central

    SAVAS, Selcuk; KAVRÌK, Fevzi; KUCUKYÌLMAZ, Ebru

    2016-01-01

    ABSTRACT Objective The aim of this study was to evaluate the efficacy of CPP-ACP containing fluoride varnish for remineralizing white spot lesions (WSLs) with four different quantitative methods. Material and Methods Four windows (3x3 mm) were created on the enamel surfaces of bovine incisor teeth. A control window was covered with nail varnish, and WSLs were created on the other windows (after demineralization, first week and fourth week) in acidified gel system. The test material (MI Varnish) was applied on the demineralized areas, and the treated enamel samples were stored in artificial saliva. At the fourth week, the enamel surfaces were tested by surface microhardness (SMH), quantitative light-induced fluorescence-digital (QLF-D), energy-dispersive spectroscopy (EDS) and laser fluorescence (LF pen). The data were statistically analyzed (α=0.05). Results While the LF pen measurements showed significant differences at baseline, after demineralization, and after the one-week remineralization period (p<0.05), the difference between the 1- and 4-week was not significant (p>0.05). With regards to the SMH and QLF-D analyses, statistically significant differences were found among all the phases (p<0.05). After the 1- and 4-week treatment periods, the calcium (Ca) and phosphate (P) concentrations and Ca/P ratio were higher compared to those of the demineralization surfaces (p<0.05). Conclusion CPP-ACP containing fluoride varnish provides remineralization of WSLs after a single application and seems suitable for clinical use. PMID:27383699

  14. Effect of pH of amine fluoride containing toothpastes on enamel remineralization in vitro

    PubMed Central

    Arnold, Wolfgang H; Haase, Anabel; Hacklaender, Julia; Gintner, Zeno; Bánóczy, Jolan; Gaengler, Peter

    2007-01-01

    Background One of the important factors of the demineralization and remineralization equilibrium of enamel is the pH of the surrounding solutions. Effort has been laid in the formulation of different fluoride compounds and the fluoride content in toothpastes but much less is known about the influence of the pH of the toothpastes on their effectiveness. It was therefore the aim of this study to investigate the influence of different pH levels on enamel remineralization in an in vitro experiment using polarization light microscopy and EDX quantitative element analysis. Methods A 5 × 5 mm window on the enamel surface of 40 caries free extracted human premolars was demineralized in a hydroxyethylcellulose solution at pH 4.8. The teeth were divided into 8 groups and the lower half of the window was covered with varnish serving as control. Each group was then immersed in toothpaste slurry containing amine fluoride (1400 ppm) at pH 4.1, 4.5, 5.1 and 6.9 or control toothpaste slurry without fluoride at pH 4.3, 4.7, 5.3 and 7.0. Serial sections were cut through the lesions and investigated with polarization light microscopy and quantitative EDX element analysis. Results The PLM results showed a decreased porous volume of the body of the lesion after incubation with fluoridated toothpaste at pH 4.53 and 5.16. No differences between the experimental window and the control window were found in the other groups. The quantitative element analysis showed no differences in the element content of any of the groups. Conclusion From the results it can be concluded that slightly acidified fluoridated dentifrices may have a certain positive effect on enamel remineralization. PMID:17941981

  15. Comparison of Various Concentrations of Tricalcium Phosphate Nanoparticles on Mechanical Properties and Remineralization of Fissure Sealants

    PubMed Central

    Tavassoli-Hojjati, Sara; Atai, Mohammad; Haghgoo, Roza; Rahimian-Imam, Sara; Kameli, Somayeh; Ahmaian-Babaki, Fatemeh; Hamzeh, Faezeh; Ahmadyar, Maryam

    2014-01-01

    Objective: The aim of this study was to investigate the mechanical properties (flexural strength, micro-shear bond strength) and remineralizing potential of fissure sealants by adding various concentrations of β-tricalcium phosphate nanoparticles. Materials and Methods: This in-vitro study consisted of five experimental groups containing prepared nano-fisssure sealants (1–5 wt.% β-TCP nanoparticles) and two control groups containing a prepared and a commercial fissure sealant. Flexural/micro-shear bond strength values were measured using Zwick test machine. Cavities on sixty healthy premolar teeth were filled with the fissure sealants containing 0–5 wt.% of nano β-TCP. The samples were assessed for remineralization under scanning electron microscopy (SEM) and EDAX. Kolmogorov-Smirnov test, One-way ANOVA and Tukey’s Post Hoc analysis/HSD were used to analyze the data. Results: There was no significant difference between the flexural strengths/elastic modulus of the 0–5 wt.% nano β-TCP groups (p>0.05). The average flexural strength/elastic modulus of the prepared fissure sealant group (0%) was significantly higher than the commercial fissure sealant group (Clinpro) (p<0.05). There was no significant difference between micro-shear bond strengths of the experimental groups (1–5 wt.%), and between the commercial and the prepared (0%) fissure sealant groups (p>0.05). Examining the samples under SEM showed a significant increase in thickness of the intermediate layer with increasing concentrations of β-TCP nanoparticles (p<0.05). Conclusion: Addition of 1–5 wt.% β-TCP nanoparticles to the fissure sealants significantly increased the remineralization potential without affecting the mechanical properties. PMID:25584048

  16. Laboratory study of nitrogen and phosphorus remineralization during the decomposition of coastal plankton and seston

    NASA Astrophysics Data System (ADS)

    Garber, Jonathan H.

    1984-06-01

    The decomposition of cultured marine phytoplankton ( Skeletonema costatum) and natural estuarine seston from Narragansett Bay, RI, was studied at two temperatures (8°C and 18°C) in bottles containing sterile bay-water (30‰) and in bay-water with micro-organisms small enough to pass through a glass fibre filter (nominally < 1μ). About 50% of the particulate organic nitrogen (PON) and particulate phosphorus (PP) was immediately released to the water in dissolved organic forms from both types of organic matter. Comparison of changes in the dissolved organic nitrogen (DON) fraction in the sterile and non-sterile systems indicated that nearly all of the DON initially released was subsequently remineralized. Ammonification proceeded only in non-sterile bay-water. 20-25% of the PP was converted to dissolved inorganic-P (DIP) fraction after only 7 h in both sterile and non-sterile bay-water. Following autolytic releases of DON, DOP and DIP the initial rates of N and P remineralization were temperature dependent: Q 10 values for PON and PP decay during first phase of microbially mediated decomposition ranged from 1·3 to 6·4. Rates of remineralization then slowed so that about equal amounts of nutrients were remineralized (45-50% of the N and 57-60% of the P in the phytoplankton and 60-63% of the N and 36-60% of the P in the natural seston) after 30 days storage at either temperature. During 30 days of decomposition in non-sterile seawater the N/P ratios in the dissolved inorganic fractions converged on the ratios of total-N/total-P initially present in the bottles. Kinetic analysis of the decay of total organic-N (TON) and total organic-P (TOP) in the non-sterile systems and analysis of similar sets found in the literature showed that the initial stages of the decomposition of N and P from planktonic POM in vitro could be modelled as the sequential decay, at first-order rates, of two particulate fractions. The first, more labile, fraction comprised about 60% of the

  17. Structural investigations on differently sized monodisperse iron oxide nanoparticles synthesized by remineralization of apoferritin molecules

    NASA Astrophysics Data System (ADS)

    Ullrich, Aladin; Horn, Siegfried

    2013-08-01

    We have investigated the structure of iron oxide nanoparticles produced by remineralization and thermal treatment of horse spleen apoferritin molecules. The described procedure allows to synthesize particles with diameters ranging from 4 to 7 nm in size. Atomic force microscopy and transmission electron microscopy (TEM) investigations were performed for shape and size determination, whereas energy-dispersive X-ray (TEM-EDX), high-resolution TEM, and electron diffraction measurements revealed the chemical composition and crystal structure of the particles. We found predominantly single crystalline nanoparticles with a hematite-like (α-Fe2O3) structure.

  18. Nondestructive Monitoring of the Repair of Natural Occlusal Lesions using Cross – Polarization Optical Coherence Tomography

    PubMed Central

    Kang, Hobin; Darling, Cynthia L.; Fried, Daniel

    2012-01-01

    Previous remineralization studies employing cross polarization sensitive optical coherence tomography (CP-OCT), have been limited to the repair of artificial enamel-like lesions. In this study we attempted to remineralize existing occlusal lesions on extracted teeth. Lesions were imaged before and after exposure to an acidic remineralization regimen and the integrated reflectivity and lesion depth was calculated. Automated integration routines worked well for assessing the integrated reflectivity for the lesion areas after remineralization. Polarized light microscopy was also used to examine the lesions areas after sectioning the teeth. An acidic remineralization solution was used to remineralize the lesions. The integrated reflectivity significantly increased after exposure to the remineralization solution which suggests that the acidic solution caused additional demineralization as opposed to the desired remineralization. PMID:23538837

  19. Biotic and abiotic retention, recycling and remineralization of metals in the ocean

    NASA Astrophysics Data System (ADS)

    Boyd, Philip W.; Ellwood, Michael J.; Tagliabue, Alessandro; Twining, Benjamin S.

    2017-03-01

    Trace metals shape both the biogeochemical functioning and biological structure of oceanic provinces. Trace metal biogeochemistry has primarily focused on modes of external supply of metals from aeolian, hydrothermal, sedimentary and other sources. However, metals also undergo internal transformations such as abiotic and biotic retention, recycling and remineralization. The role of these internal transformations in metal biogeochemical cycling is now coming into focus. First, the retention of metals by biota in the surface ocean for days, weeks or months depends on taxon-specific metal requirements of phytoplankton, and on their ultimate fate: that is, viral lysis, senescence, grazing and/or export to depth. Rapid recycling of metals in the surface ocean can extend seasonal productivity by maintaining higher levels of metal bioavailability compared to the influence of external metal input alone. As metal-containing organic particles are exported from the surface ocean, different metals exhibit distinct patterns of remineralization with depth. These patterns are mediated by a wide range of physicochemical and microbial processes such as the ability of particles to sorb metals, and are influenced by the mineral and organic characteristics of sinking particles. We conclude that internal metal transformations play an essential role in controlling metal bioavailability, phytoplankton distributions and the subsurface resupply of metals.

  20. The effect of different fluoride application methods on the remineralization of initial carious lesions

    PubMed Central

    2016-01-01

    Objectives The purpose of this study was to assess the effect of single and combined applications of fluoride on the amount of fluoride release, and the remineralization and physical properties of enamel. Materials and Methods Each of four fluoride varnish and gel products (Fluor Protector, FP, Ivoclar Vivadent; Tooth Mousse Plus, TM, GC; 60 Second Gel, A, Germiphene; CavityShield, CS, 3M ESPE) and two fluoride solutions (2% sodium fluoride, N; 8% tin(ii) fluoride, S) were applied on bovine teeth using single and combined methods (10 per group), and then the amount of fluoride release was measured for 4 wk. The electron probe microanalysis and the Vickers microhardness measurements were conducted to assess the effect of fluoride application on the surface properties of bovine teeth. Results The amount of fluoride release was higher in combined applications than in single application (p < 0.05). Microhardness values were higher after combined applications of N with FP, TM, and CS than single application of them, and these values were also higher after combined applications of S than single application of A (p < 0.05). Ca and P values were higher in combined applications of N with TM and CS than single application of them (p < 0.05). They were also increased after combined applications of the S with A than after single application (p < 0.05). Conclusions Combined applications of fluoride could be used as a basis to design more effective methods of fluoride application to provide enhanced remineralization. PMID:27200280

  1. In vivo remineralization of dentin using an agarose hydrogel biomimetic mineralization system

    NASA Astrophysics Data System (ADS)

    Han, Min; Li, Quan-Li; Cao, Ying; Fang, Hui; Xia, Rong; Zhang, Zhi-Hong

    2017-02-01

    A novel agarose hydrogel biomimetic mineralization system loaded with calcium and phosphate was used to remineralize dentin and induce the oriented densely parallel packed HA layer on defective dentin surface in vivo in a rabbit model. Firstly, the enamel of the labial surface of rabbits’ incisor was removed and the dentin was exposed to oral environment. Secondly, the hydrogel biomimetic mineralization system was applied to the exposed dentin surface by using a custom tray. Finally, the teeth were extracted and evaluated by scanning electron microscopy, X-ray diffraction, and nanoindentation test after a certain time of mineralization intervals. The regenerated tissue on the dentin surface was composed of highly organised HA crystals. Densely packed along the c axis, these newly precipitated HA crystals were perpendicular to the underlying dental surface with a tight bond. The demineralized dentin was remineralized and dentinal tubules were occluded by the grown HA crystals. The nanohardness and elastic modulus of the regenerated tissue were similar to natural dentin. The results indicated a potential clinical use for repairing dentin-exposed related diseases, such as erosion, wear, and dentin hypersensitivity.

  2. Remineralized Bone Matrix (RBM) as a Scaffold for Bone Tissue Engineering

    PubMed Central

    Soicher, Matthew A.; Christiansen, Blaine A.; Stover, Susan M.; Leach, J. Kent; Yellowley, Clare E.; Griffiths, Leigh G.; Fyhrie, David P.

    2014-01-01

    There is a need for improved biomaterials for use in treating non-healing bone defects. A number of natural and synthetic biomaterials have been used for the regeneration of bone tissue with mixed results. One approach is to modify native tissue via decellularization or other treatment for use as natural scaffolding for tissue repair. In this study, our goal was to improve on our previously published alternating solution immersion (ASI) method to fabricate a robust, biocompatible, and mechanically competent biomaterial from natural demineralized bone matrix (DBM). The improved method includes an antigen removal (AR) treatment step which improves mineralization and stiffness while removing unwanted proteins. The chemistry of the mineral in the remineralized bone matrix (RBM) was consistent with dicalcium phosphate dihydrate (brushite), a material used clinically in bone healing applications. Mass spectrometry identified proteins removed from the matrix with AR treatment to include α-2 HS-glycoprotein and osteopontin, non-collagenous proteins (NCPs) and known inhibitors of biomineralization. Additionally, the RBM supported the survival, proliferation, and differentiation of human mesenchymal stromal cells (MSCs) in vitro as well or better than other widely used biomaterials including DBM and PLG scaffolds. DNA content increased more than 10-fold on RBM compared to DBM and PLG; likewise, osteogenic gene expression was significantly increased after 1 and 2 weeks. We demonstrated that ASI remineralization has the capacity to fabricate mechanically stiff and biocompatible RBM, a suitable biomaterial for cell culture applications. PMID:24616346

  3. Incorporation of oxidized uranium into Fe (hydr)oxides during Fe(II) catalyzed remineralization

    SciTech Connect

    Nico, Peter S.; Stewart, Brandy D.; Fendorf, Scott

    2009-07-01

    The form of solid phase U after Fe(II) induced anaerobic remineralization of ferrihydrite in the presence of aqueous and absorbed U(VI) was investigated under both abiotic batch and biotic flow conditions. Experiments were conducted with synthetic ground waters containing 0.168 mM U(VI), 3.8 mM carbonate, and 3.0 mM Ca{sup 2+}. In spite of the high solubility of U(VI) under these conditions, appreciable removal of U(VI) from solution was observed in both the abiotic and biotic systems. The majority of the removed U was determined to be substituted as oxidized U (U(VI) or U(V)) into the octahedral position of the goethite and magnetite formed during ferrihydrite remineralization. It is estimated that between 3% and 6% of octahedral Fe(III) centers in the new Fe minerals were occupied by U(VI). This site specific substitution is distinct from the non-specific U co-precipitation processes in which uranyl compounds, e.g. uranyl hydroxide or carbonate, are entrapped with newly formed Fe oxides. The prevalence of site specific U incorporation under both abiotic and biotic conditions and the fact that the produced solids were shown to be resistant to both extraction (30 mM KHCO{sub 3}) and oxidation (air for 5 days) suggest the potential importance of sequestration in Fe oxides as a stable and immobile form of U in the environment.

  4. Marine phosphate oxygen isotopes and organic matter remineralization in the oceans

    PubMed Central

    Colman, Albert S.; Blake, Ruth E.; Karl, David M.; Fogel, Marilyn L.; Turekian, Karl K.

    2005-01-01

    We show that the isotopic composition of oxygen (δ18O) in dissolved inorganic phosphate (Pi) reveals the balance between Pi transport and biological turnover rates in marine ecosystems. Our δ18Op of Pi (δ18Op) measurements herein indicate the importance of cell lysis in the regeneration of Pi in the euphotic zone. Depth profiles of the δ18Op in the Atlantic and Pacific Oceans are near a temperature-dependent isotopic equilibrium with water. Small deviations from equilibrium below the thermocline suggest that P remineralization in the deep ocean is a byproduct of microbial carbon and energy requirements. However, isotope effects associated with phosphohydrolase enzymes involved in P remineralization are quite large and could potentially lead to significant disequilibration of Pi oxygen. The observed near equilibration of deep water Pi likely calls for continued slow rates of microbial uptake and release of Pi and/or extracellular pyrophosphatase-mediated oxygen exchange between water and Pi along the deep water flow path. PMID:16141319

  5. In vivo remineralization of dentin using an agarose hydrogel biomimetic mineralization system

    PubMed Central

    Han, Min; Li, Quan-Li; Cao, Ying; Fang, Hui; Xia, Rong; Zhang, Zhi-Hong

    2017-01-01

    A novel agarose hydrogel biomimetic mineralization system loaded with calcium and phosphate was used to remineralize dentin and induce the oriented densely parallel packed HA layer on defective dentin surface in vivo in a rabbit model. Firstly, the enamel of the labial surface of rabbits’ incisor was removed and the dentin was exposed to oral environment. Secondly, the hydrogel biomimetic mineralization system was applied to the exposed dentin surface by using a custom tray. Finally, the teeth were extracted and evaluated by scanning electron microscopy, X-ray diffraction, and nanoindentation test after a certain time of mineralization intervals. The regenerated tissue on the dentin surface was composed of highly organised HA crystals. Densely packed along the c axis, these newly precipitated HA crystals were perpendicular to the underlying dental surface with a tight bond. The demineralized dentin was remineralized and dentinal tubules were occluded by the grown HA crystals. The nanohardness and elastic modulus of the regenerated tissue were similar to natural dentin. The results indicated a potential clinical use for repairing dentin-exposed related diseases, such as erosion, wear, and dentin hypersensitivity. PMID:28167823

  6. Pulse thermography for quantitative nondestructive evaluation of sound, de-mineralized and re-mineralized enamel

    NASA Astrophysics Data System (ADS)

    Ando, Masatoshi; Sharp, Nathan; Adams, Douglas

    2012-04-01

    Current limitations for diagnosing mineralization state of tooth enamel can lead to improper surgical treatments. A method is investigated by which the tooth health state is characterized according to its thermal response, which is hypothesized to be sensitive to increased porosity in enamel that is caused by demineralization. Several specimens consisting of previously extracted human teeth a re prepared by exposure to Streptococcus mutans A32-2 in trypticase-soy-borth supplemented with 5% sucrose at 37°C for 3 or 6 days to de-mineralize two 1×1mm2-windows on each tooth. One of these windows is then re-mineralized with 250 or 1,100ppm-F as NaF for 10 days by pH-cyclic-model. Pulse thermography is used to measure the thermal response of these sections as well as the sound (healthy) portions of the specimen. A spatial profile of the thermal parameters of the specimens is then extracted from the thermography data and are used to compare the sound, de-mineralized, and re-mineralized areas. Results show that the thermal parameters are sensitive to the mineralization state of the tooth and that this method has the potential to accurately and quickly characterize the mineralization state of teeth, thereby allowing future dentists to make informed decisions regarding the best treatment for teeth that have experienced demineralization.

  7. The effect of two remineralizing agents and natural saliva on bleached enamel hardness

    PubMed Central

    Heshmat, Haleh; Ganjkar, Maryam Hoorizad; Miri, Yasaman; Fard, Mohamad Javad Kharrazi

    2016-01-01

    Background: In order to compensate the adverse consequences of bleaching agents, the use of fluoride-containing remineralizing agents has been suggested by many researchers. The aim of this study was to compare the effect of applying two remineralizing materials on bleached enamel hardness and in comparison to natural saliva. Materials and Methods: In this experimental study, 30 enamel samples of sound human permanent molars were prepared for this study. Microhardness (MH) of all specimens was measured and 35% hydrogen peroxide was applied 3 times to the specimens. After completion of the bleaching process, MH of samples was measured and then enamel specimens were divided into three groups each of 10, specimens of groups 1 and 2 were subjected to daily application of hydroxyl apatite (Remin Pro) and casein phosphopeptide amorphous calcium phosphate fluoride (CPP-ACPF) (MI Paste Plus) pastes, respectively, for 15 days. In group 3, the specimens were stored in the operators' natural saliva at room temperature in this period of time. Final MH of all groups was measured. The data were analyzed using repeated measures ANOVA (α = 0.05). Results: The hardness significantly decreased in all groups following bleaching. Application of either Remin Pro, CPP-ACPF or natural saliva increased the hardness significantly. The hardness of the three test groups after 15 days were statistically similar to each other. Conclusion: The hardness of enamel increases eventually after exposure to either MI Paste Plus, Remin Pro or natural saliva. PMID:26962316

  8. Gonzalez Regimen (PDQ®)—Patient Version

    Cancer.gov

    Expert-reviewed information summary about the Gonzalez regimen as a treatment for people with cancer. Note: The information in this summary is no longer being updated and is provided for reference purposes only.

  9. Casein phosphopeptide-amorphous calcium phosphate and glass ionomer show distinct effects in the remineralization of proximal artificial caries lesion in situ.

    PubMed

    Thepyou, Rathapong; Chanmitkul, Wanvipa; Thanatvarakorn, Ornnicha; Hamba, Hidenori; Chob-Isara, Wanwalai; Trairatvorakul, Chutima; Tagami, Junji

    2013-01-01

    This study aimed to compare the ability of casein-phosphopeptide amorphous-calcium-phosphate (CPP-ACP) and glass-ionomer (GI) in remineralizing proximal artificial caries lesions (ACLs). Molar enamel-slabs were divided into: original-lesion control, intra-oral controls, and experimental (CPP-ACP or GI) groups. Specimens received ACLs and were bonded on subject maxillary first molars. After 4-weeks, mineral density (MD) was analyzed by μCT. Compared to control, CPP-ACP increased MD at 0-38/68-84 microns and the GI group had an increase at 0-68 microns, with a greater increase in MD compared to the CPP-ACP group from 0-53 microns. The mean percent remineralization (%R) showed differences between the GI, CPP-ACP groups and their paired controls. GI tended to increase remineralization more than CPP-ACP. In conclusion, CPP-ACP and GI demonstrated distinct remineralizing ability. GI induced greater remineralization in the superficial lesion, while CPP-ACP remineralized the lesion body. Their effects on percent remineralization and reducing lesion depth of proximal ACLs were similar.

  10. Bowel preparation regimens for colon capsule endoscopy: a review

    PubMed Central

    Nigar, Sofia; Paleti, Vani; Lane, Devin; Duddempudi, Sushil

    2014-01-01

    Colon capsule endoscopy (CCE) is being actively evaluated as an emerging complementary or alternative procedure for evaluation of the colon. The yield of CCE is significantly dependent on the quality of bowel preparation. In addition to achieving a stool-free colon the bowel preparation protocols need to decrease bubble effect and aid propulsion of the capsule. An extensive English literature search was done using PubMed with search terms of colon capsule endoscopy, PillCam and bowel preparation. Full-length articles which met the criteria were included for review. A total of 12 studies including 1149 patients were reviewed. There was significant variability in the type of bowel preparation regimens. Large-volume (3–4 liters) polyethylene glycol (PEG) was the most widely used laxative. Lower volumes of PEG showed comparable results but larger studies are needed to determine efficacy. Sodium phosphate was used as an effective booster in most studies. Magnesium citrate and ascorbic acid are emerging as promising boosters to replace sodium phosphate when it is contraindicated. The potential benefit of prokinetics needs further evaluation. Over the past decade there has been significant improvement in the bowel preparation regimens for CCE. Further experience and studies are likely to standardize the bowel preparation regimens before CCE is adopted into routine clinical practice. PMID:24790642

  11. Insights into particle formation and remineralization using the short-lived radionuclide, Thoruim-234

    NASA Astrophysics Data System (ADS)

    Maiti, Kanchan; Benitez-Nelson, Claudia R.; Buesseler, Ken O.

    2010-08-01

    Simple mass balance models are applied to a high resolution 234Th profile from the northwest Pacific to examine the magnitude, rate, and depth distribution of particle remineralization processes below the euphotic zone (Ez). Here, excess 234Th (234Th > 238U) below the Ez is attributed to fragmentation processes that result in the conversion of sinking to non-sinking particles. By considering particulate organic carbon (POC) to 234Th ratios on particles, we show that POC flux attenuation is larger than for 234Th, which we attribute to bacterial and zooplankton consumption of sinking POC. Three case studies are used to demonstrate how different combinations of particle fragmentation and POC respiration impact flux attenuation below the Ez. When sampled with high vertical resolution and precision, 234Th and POC/234Th ratios provide insights into both export from the Ez and the extent to which sinking particle fluxes and associated minerals are attenuated with depth.

  12. Remineralizing efficacy of a CPP-ACP cream on enamel caries lesions in situ.

    PubMed

    Meyer-Lueckel, Hendrik; Wierichs, Richard J; Schellwien, Timo; Paris, Sebastian

    2015-01-01

    The aim of this double-blind, randomized, cross-over in situ study was to compare the remineralizing effects induced by the application of casein phosphopeptide-stabilized amorphous calcium phosphate complexes (CPP-ACP)-containing cream (without fluoride) after the use of fluoride toothpaste with the prolonged use of fluoride toothpaste on enamel caries lesions in situ. During each of three experimental legs of 4 weeks, 13 participants wore intra-oral mandibular appliances with 8 pre-demineralized bovine enamel specimens in the vestibular flanges mimicking either 'easily cleanable' or 'proximal' surfaces (n = 312). The three randomly allocated treatments were as follows: (1) application of CPP-ACP-containing cream (GC Tooth Mouse, non-fluoride) after the use of fluoride toothpaste (1,400 ppm NaF; TM), (2) prolonged application of fluoride toothpaste (1,400 ppm NaF; positive control, PC) and (3) prolonged application of fluoride-free toothpaste (negative control, NC). Additionally, one of each of the two flanges was brushed twice daily with the respective toothpaste. The differences in integrated mineral loss as assessed by transversal microradiography were calculated between values before and after the in situ period. Changes in mineral loss were analysed for those pairs of subgroups differing in only one of the three factors (intervention, brushing and position). The PC treatment induced a significantly higher mineral gain compared with the TM and NC treatments. No significant differences between TM and NC for both positions were observed. In conclusion, the additional use of a CPP-ACP-containing cream seems to be less efficacious in remineralizing caries lesions than the prolonged application of fluoride toothpaste.

  13. Toward the definition of immunosuppressive regimens with antitumor activity.

    PubMed

    Casadio, F; Croci, S; D'Errico Grigioni, A; Corti, B; Grigioni, W F; Landuzzi, L; Lollini, P-L

    2005-06-01

    Immunosuppressive therapies associated with organ transplantation produce an increased risk of cancer development. Malignancies are increased in transplant recipients because of the impaired immune system. Moreover, experimental data point to a tumor-promoting activity of various immunosuppressive agents. In this study, we compared the effects of 4 immunosuppressive agents with different mechanisms of action (cyclosporine, rapamycin, mycophenolic acid, and leflunomide) on the in vitro growth of various tumor cell lines and umbilical vein endothelial cells. To varying degrees rapamycin (10 ng/mL), mycophenolic acid (300 nmol/L), and leflunomide (30 micromol/L) highly inhibited the growth of human rhabdomyosarcoma, hepatocellular carcinoma, colorectal carcinoma, and endothelial cells. In contrast, cyclosporine (100 ng/mL) did not affect their growth. Our data suggest that regimens containing rapamycin, mycophenolic acid, or leflunomide, which have both immunosuppressive and antitumor activities, should be preferred in transplant recipients to minimize the risk of tumors.

  14. Remineralization of demineralized enamel by toothpastes: a scanning electron microscopy, energy dispersive X-ray analysis, and three-dimensional stereo-micrographic study.

    PubMed

    Gjorgievska, Elizabeta S; Nicholson, John W; Slipper, Ian J; Stevanovic, Marija M

    2013-06-01

    Remineralization of hard dental tissues is thought to be a tool that could close the gap between prevention and surgical procedures in clinical dentistry. The purpose of this study was to examine the remineralizing potential of different toothpaste formulations: toothpastes containing bioactive glass, hydroxyapatite, or strontium acetate with fluoride, when applied to demineralized enamel. Results obtained by scanning electron microscopy (SEM) and SEM/energy dispersive X-ray analyses proved that the hydroxyapatite and bioactive glass-containing toothpastes were highly efficient in promoting enamel remineralization by formation of deposits and a protective layer on the surface of the demineralized enamel, whereas the toothpaste containing 8% strontium acetate and 1040 ppm fluoride as NaF had little, if any, remineralization potential. In conclusion, the treatment of demineralized teeth with toothpastes containing hydroxyapatite or bioactive glass resulted in repair of the damaged tissue.

  15. EDX-Element Analysis of the In Vitro Effect of Fluoride Oral Hygiene Tablets on Artificial Caries Lesion Formation and Remineralization in Human Enamel.

    PubMed

    Eggerath, J; Kremniczky, T; Gaengler, P; Arnold, W H

    2011-01-01

    Aim of this in-vitro-study was to assess the remineralization potential of a tooth cleaning tablet with different fluoride content quantitatively using EDX analysis.Twenty three caries free impacted third molars were examined; enamel surfaces were wax coated leaving two 3x4mm windows for exposure to demineralization/remineralization cycles. The teeth were randomly assigned to 4 groups of 5 control and 6 experimental teeth each. Demineralization by standardized HEC-gel, pH 4.7 at 37°C for 72h, was alternated by rinsing in remineralization solution, pH 7.0 at 37°C for 72h, total challenge time 432h. The negative control group N was treated during remineralization cycles with saline; positive control group P was treated with remineralization solution; experimental group D1 was exposed to remineralization solution containing Denttabs(®)-tablets with 1450 ppm F; experimental group D2 was exposed to remineralization solution and Denttabs(®)-tablets with 4350 ppm F. Each tooth was cut into serial sections and analyzed by scanning electron microscopy with EDX element analysis for assessment of the different zones of the lesions in 3 representative sections. Statistical analysis was based on the AVOVA test for repeated measurements and post hoc Bonferroni adjustment. The results showed a significantly higher Ca and P content in the body of the lesion in both fluoride treated groups compared to the controls. It can be concluded that higher concentrations of NaF may be more effective in remineralization of early advanced caries lesions.

  16. Eroded enamel lesion remineralization by saliva as a possible factor in the site-specificity of human dental erosion.

    PubMed

    Amaechi, B T; Higham, S M

    2001-08-01

    The composition and flow of saliva, which determine its functions, vary within intraoral sites and among individuals. Also, the susceptibility to tooth erosion reportedly varies among individuals and within the dental arches. A possible effect of saliva on early-eroded lesions may be a contributory factor. The aims here were firstly to determine the remineralization of eroded enamel lesions by saliva, and secondly to investigate any variation of this remineralization within the dental arches and among individuals. Early enamel erosion was produced on human premolars using orange juice. Control sections and two test slabs were cut from each tooth. The two slabs from the same lesion were bonded with composite resins to the palatal surface of upper right lateral incisor teeth and the lingual surface of the lower right lateral incisor teeth of volunteers, who then chewed a sugar-free gum four times daily. After 28-day intraoral exposure, mineral loss (DeltaZ) and lesion depth (ld) were quantified using microradiography and the data analysed by paired t-test (n=10, alpha=0.05). Mean DeltaZ was significantly lower in the group of slabs positioned palatally (P<0.001) and lingually (P<0.001) when compared with the control group, and in the lingually placed group when compared with the palatally positioned (P<0.01). A significantly lower ld was observed in the group of slabs positioned palatally (P<0.05) and lingually (P<0.001) when compared with the control group, and in the lingually positioned group when compared with the palatally placed (P<0.05). It was concluded that saliva can remineralize early enamel erosion, and that the degree of remineralization varies within intraoral sites and may be responsible for the differing susceptibility to erosion within the dental arches.

  17. Role of fluoridated carbamide peroxide whitening gel in the remineralization of demineralized enamel: An in vitro study

    PubMed Central

    Bollineni, Swetha; Janga, Ravi Kumar; Venugopal, L.; Reddy, Indukuri Ravikishore; Babu, P. Ravisekhar; Kumar, Sunil S.

    2014-01-01

    Introduction: The use of self-administered carbamide peroxide bleaching gels has become increasingly popular for whitening of discolored vital teeth. Studies have reported that its use may induce increased levels of sensitivity and surface roughness of the tooth due to demineralization. This study evaluates the effect of fluoride addition to the bleaching agent – its remineralizing capacity and alterations in the whitening properties. Materials and Methods: Twenty-four extracted lower third molar teeth, with the pretreatment shade determined, were taken up in the study. Each tooth was sectioned into four and labeled as groups A, B, C, and D. The tooth quadrants in group A-C were demineralized; groups A and B were treated with 10% carbamide peroxide gel (group-A without fluoride and group-B with 0.463% fluoride addition) (no further treatment was carried out for group c) group-D remained as the control. The post-treatment shade was determined. The tooth samples were sectioned (approximately 200 μm) for evaluation under a light microscope. The depth of demineralization was analyzed at five different equidistant points. Statistical analysis was carried out with t-tests, accepting ≤0.05 as significant. Results and Conclusion: Addition of fluoride caused remineralization of demineralized enamel. The tooth whitening system showed that the remineralization properties did not affect the whitening properties. PMID:25254197

  18. Remineralization of particulate authigenic trace metals in the middle Atlantic Bight: Implications for proxies of export production

    NASA Astrophysics Data System (ADS)

    Kumar, N.; Anderson, R. F.; Biscaye, P. E.

    1996-09-01

    Samples collected by time-series sediment traps deployed in the Middle Atlantic Bight were studied to better understand the formation, and preservation, of particulate authigenic forms of trace metals (Cu, Ni, Ba) That hold potential to serve as proxies in the sedimentary record of past changes in the flux of biogenic detritus sinking from the surface ocean into the deep sea (export production). Particulate biogenic and authigenic phases are extremely labile, as evidenced by the observation that as much as 70% of the particulate fluxes of organic carbon and of certain metals (Cu, Ni, and Mn), and up to 25% of the particulate fluxes of authigenic Ba and of opal collected by sediment traps are released rapidly into solution during the time period between particle collection and trap retrieval. Further remineralization on the seabed reduces concentrations of authigenic Cu and Ni in surface sediments below the limit of detection. Approximately 80% of authigenic Ba is remineralized during early diagenesis on the seabed, much more than is expected for conditions of high sediment mass accumulation rate that exist in the study area. Extensive remineralization during early diagenesis, combined with large corrections required to remove the aluminosilicate contribution to the concentrations of Cu, Ni, and Ba in sediments, preclude the successful use of down-core profiles of these trace metals to reconstruct past changes in export production of the Middle Atlantic Bight. Similar problems are likely to plague paleoproductivity reconstructions in other ocean-margin regions, or wherever high fluxes of aluminosilicate phases occur.

  19. Shear Bond Strength of Orthodontic Brackets Fixed with Remineralizing Adhesive Systems after Simulating One Year of Orthodontic Treatment.

    PubMed

    Bezerra, Gisele Lima; Torres, Carlos Rocha Gomes; Tonetto, Mateus Rodrigues; Borges, Alvaro Henrique; Kuga, Milton Carlos; Bandeca, Matheus Coelho; Firoozmand, Leily Macedo

    2015-01-01

    The objective of this study is to assess, in vitro, the shear bond strength of orthodontic brackets fixed with remineralizing adhesive systems submitted to thermomechanical cycling, simulating one year of orthodontic treatment. Sixty-four bovine incisor teeth were randomly divided into 4 experimental groups (n = 16): XT: Transbond XT, QC: Quick Cure, OL: Ortholite Color, and SEP: Transbond Plus Self-Etching Primer. The samples were submitted to thermomechanical cycling simulating one year of orthodontic treatment. Shear bond strength tests were carried out using a universal testing machine with a load cell of 50 KgF at 0.5 mm/minute. The samples were examined with a stereomicroscope and a scanning electron microscope (SEM) in order to analyze enamel surface and Adhesive Remnant Index (ARI). Kruskal-Wallis and Mann-Whitney (with Bonferroni correction) tests showed a significant difference between the studied groups (p < 0.05). Groups XT, QC, and SEP presented the highest values of adhesive resistance and no statistical differences were found between them. The highest frequency of failures between enamel and adhesive was observed in groups XT, QC, and OL. Quick Cure (QC) remineralizing adhesive system presented average adhesive resistance values similar to conventional (XT) and self-etching (SEP) adhesives, while remineralizing system (OL) provided the lowest values of adhesive resistance.

  20. Shear Bond Strength of Orthodontic Brackets Fixed with Remineralizing Adhesive Systems after Simulating One Year of Orthodontic Treatment

    PubMed Central

    Bezerra, Gisele Lima; Torres, Carlos Rocha Gomes; Tonetto, Mateus Rodrigues; Borges, Alvaro Henrique; Kuga, Milton Carlos; Bandeca, Matheus Coelho; Firoozmand, Leily Macedo

    2015-01-01

    The objective of this study is to assess, in vitro, the shear bond strength of orthodontic brackets fixed with remineralizing adhesive systems submitted to thermomechanical cycling, simulating one year of orthodontic treatment. Sixty-four bovine incisor teeth were randomly divided into 4 experimental groups (n = 16): XT: Transbond XT, QC: Quick Cure, OL: Ortholite Color, and SEP: Transbond Plus Self-Etching Primer. The samples were submitted to thermomechanical cycling simulating one year of orthodontic treatment. Shear bond strength tests were carried out using a universal testing machine with a load cell of 50 KgF at 0.5 mm/minute. The samples were examined with a stereomicroscope and a scanning electron microscope (SEM) in order to analyze enamel surface and Adhesive Remnant Index (ARI). Kruskal-Wallis and Mann-Whitney (with Bonferroni correction) tests showed a significant difference between the studied groups (p < 0.05). Groups XT, QC, and SEP presented the highest values of adhesive resistance and no statistical differences were found between them. The highest frequency of failures between enamel and adhesive was observed in groups XT, QC, and OL. Quick Cure (QC) remineralizing adhesive system presented average adhesive resistance values similar to conventional (XT) and self-etching (SEP) adhesives, while remineralizing system (OL) provided the lowest values of adhesive resistance. PMID:26380371

  1. Evaluation of remineralization capacity of casein phosphopeptide-amorphous calcium phosphate on the carbamide peroxide treated enamel

    PubMed Central

    Penumatsa, Narendra Varma; Kaminedi, Raja Rajeswari; Baroudi, Kusai; Barakath, Ola

    2015-01-01

    Objective: The aim of this study was to evaluate the potential of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) in remineralizing the bleached enamel surface using micro-hardness. Materials and Methods: Thirty human enamel slabs were randomly divided into three groups (n = 10). Groups A and B were exposed to 20% carbamide peroxide and 35% carbamide peroxide gel, respectively. After the exposure to the bleaching agent, the slabs were kept in artificial saliva for 1-week. Group C (control group) were kept in artificial saliva for 1-week. Vickers micro-hardness test was performed by Leica VMHT-Mot micro-hardness tester. CPP-ACP (Gc Tooth Mousse, Melbourne, Australia) was then applied to specimens of Groups A and B for 3 min for 2 weeks. Micro-hardness values of postbleach Group A (Ar) and Group B (Br) were recorded and statistically analyzed by paired t-test and one-way analysis of variance at the significance level of α =0.05. Results: There was a significant decrease in micro-hardness of enamel in carbamide peroxide bleached groups. However, there was a significant increase in micro-hardness after the remineralization by CPP-ACP and the extent of remineralization is more for the Group B. Conclusions: That bleaching agents reduced enamel micro-hardness and the use of CPP-ACP after bleaching can significantly enhance the micro-hardness of bleached enamel. PMID:26538923

  2. Effect of dentifrice containing fluoride and/or baking soda on enamel demineralization/remineralization: an in situ study.

    PubMed

    Cury, J A; Hashizume, L N; Del Bel Cury, A A; Tabchoury, C P

    2001-01-01

    The additive effect of baking soda on the anticariogenic effect of fluoride dentifrice is not well established. To evaluate it, a crossover in situ study was done in three phases of 28 days. Volunteers, using acrylic palatal appliances containing four human enamel blocks, two sound (to evaluate demineralization) and two with artificial caries lesions (to evaluate remineralization), took part in this study. During each phase, 10% sucrose solution was dripped (3 times a day) only onto the sound blocks. After 10 min, a slurry of placebo, fluoride (F) or fluoride and baking soda (F+NaHCO(3)) dentifrice was dripped onto all enamel blocks. The results showed a higher F concentration in dental plaque formed during treatment with F+NaHCO(3) than placebo (p<0.05), but the difference related to F dentifrice was not significant. The enamel demineralization was lower, and remineralization was greater, after treatment with F+NaHCO(3) than placebo (p<0.05), but the difference related to F dentifrice was not significant. The data suggest that baking soda neither improves nor impairs the effect of F dentifrice on reduction of demineralization and enhancement of remineralization of enamel.

  3. Inconsistencies between (14)C and short-lived radionuclides-based sediment accumulation rates: Effects of long-term remineralization.

    PubMed

    Baskaran, M; Bianchi, T S; Filley, T R

    2016-09-06

    (14)C is the most widely utilized geochronometer to investigate geological, geochemical and geophysical problems over the past 5 decades. Establishment of precise sedimentation rates is crucial for the reconstruction of paleo-climate, -ecological and - environmental studies when extrapolation of sedimentation rates is utilized for time scales beyond the dating range. However, agreement between short-term and long-term sedimentation rates in anthropogenically unperturbed sediment cores has not been shown. Here we show that the AMS (14)C-based long-term mass accumulation rate (MAR) of an organic-rich (>70%) sediment core from Mud Lake, Florida to be ∼5 times lower than the short-term MAR obtained using (239,240)Pu, (137)Cs and excess (210)Pb ((210)Pbxs). The measured sediment inventories of (210)Pbxs, (137)Cs and (239,240)Pu are comparable to the atmospheric fallout for the sampling site, indicating very little accelerated sediment erosion over the past several decades. Presence of sharp fallout peaks of (239,240)Pu indicates very little sediment mixing. The penetration depths of (137)Cs and (239,240)Pu were found to be much deeper than expected and this is attributed to their post-depositional mobility. MAR calculated using (14)C-ages in successive layers also indicated decreasing MARs with depth, and was reflective of progressive remineralization. Using first-order kinetics, the sediment remineralization rate was found to be 4.4 × 10(-4) y(-1) and propose that over the long-term, remineralization of organic-rich sediment affected the long-term MAR, but not the ratio of (14)C/(12)C. Thus, the MAR and linear sedimentation rate obtained using (14)C (and other isotope-based methods) could be erroneous, although (14)C ages may not be affected by such remineralization. Long-term remineralization rates of organic matter has a direct bearing on the biogeochemical cycling of elements in aqueous systems and mass balance of elements needs to be taken into consideration.

  4. Controlled remineralization of enamel in the presence of amelogenin and fluoride.

    PubMed

    Fan, Yuwei; Sun, Zhi; Moradian-Oldak, Janet

    2009-02-01

    Reconstructing enamel-like structures on teeth have been an important topic of study in the material sciences and dentistry. The important role of amelogenin in modulating the mineralization of organized calcium phosphate crystals has been previously reported. We used amelogenin and utilized a modified biomimetic deposition method to remineralize the surface of etched enamel to form mineral layers containing organized needle-like fluoridated hydroxyapatite crystals. The effect of a recombinant amelogenins (rP172) on the microstructure of the mineral in the coating was analyzed by SEM, XRD and FT-IR. At rP172 concentrations below 33 microg/mL, no significant effect was observed. In the presence of 1 mg/L F and at a concentration of 33 microg/mL rP172, formation of fused crystals growing from the enamel surface was initiated. Amelogenin promoted the oriented bundle formation of needle-like fluoridated hydroxyapatite in a dose dependent manner. Biomimetic synthesis of the amelogenin fluoridated hydroxyapatite nano-composite is one of the primary steps towards the development and design of novel biomaterial for future application in reparative and restorative dentistry.

  5. Controlled remineralization of enamel in the presence of amelogenin and fluoride

    PubMed Central

    Fan, Yuwei; Sun, Zhi; Moradian-Oldak, Janet

    2008-01-01

    Reconstructing enamel-like structures on teeth has been an important topic of study in the material sciences and dentistry. The important role of amelogenin in modulating the mineralization of organized calcium phosphate crystals has been previously reported. We used amelogenin and utilized a modified biomimetic deposition method to remineralize the surface of etched enamel to form mineral layers containing organized needle-like fluoridated hydroxyapatite crystals. The effect of a recombinant amelogenins (rP172) on the microstructure of the mineral in the coating was analyzed by SEM, XRD and FT-IR. At rP172 concentrations below 33 μg/mL, no significant effect was observed. In the presence of 1 mg/L F and at a concentration of 33 μg/mL rP172, formation of fused crystals growing from the enamel surface was initiated. Amelogenin promoted the oriented bundle formation of needle-like fluoridated hydroxyapatite in a dose dependent manner. Biomimetic synthesis of the amelogenin fluoridated hydroxyapatite nano-composite is one of the primary steps towards the development and design of novel biomaterial for future application in reparative and restorative dentistry. PMID:18996587

  6. Impact of an Anticaries Mouthrinse on In Vitro Remineralization and Microbial Control

    PubMed Central

    Sun, Frank C.; Engelman, E. Eric; McGuire, James A.; Kosmoski, Gabrielle; Carratello, Lauren; Ricci-Nittel, Danette; Zhang, Jane Z.; Schemehorn, Bruce R.; Gambogi, Robert J.

    2014-01-01

    Objective. The objective of this research was to evaluate the caries control potential of a new fluoride mouthrinse that also contained antimicrobial agents and a biofilm disrupting agent using different in vitro models. Methods. Four in vitro studies were conducted to assess the performance of this three pronged approach to caries control: (1) traditional enamel fluoride uptake, (2) surface microhardness study using pH cycling model and subsequent fluoride uptake, (3) a salivary biofilm flow-through study to determine the anti-microbial activity, and (4) a single species biofilm model measuring effect on biofilm matrix disruption. Results. The data showed that a LISTERINE rinse with fluoride, essential oils and xylitol was superior in promoting enamel fluoride uptake and in enhancing antimicrobial activity over traditional commercially available fluoridated products. An increase of the surface microhardness was observed when the LISTERINE rinse was used in combination with fluoridated toothpaste versus the fluoridated toothpaste alone. Finally, it was demonstrated that xylitol solutions disrupted and reduced the biovolume of biofilm matrix of mature Streptococcus mutans. Conclusion. These in vitro studies demonstrated that a fluoride mouthrinse with antimicrobial agent and biofilm matrix disrupting agent provided multifaceted and enhanced anti-caries efficacy by promoting remineralization, reducing acidogenic bacteria and disrupting biofilm matrix. PMID:24648842

  7. Automated detection of remineralization in simulated enamel lesions with PS-OCT

    NASA Astrophysics Data System (ADS)

    Lee, Robert C.; Darling, Cynthia L.; Fried, Daniel

    2014-02-01

    Previous in vitro and in vivo studies have demonstrated that polarization-sensitive optical coherence tomography (PS-OCT) can be used to nondestructively image the subsurface structure and measure the thickness of the highly mineralized transparent surface zone of caries lesions. There are structural differences between active lesions and arrested lesions, and the surface layer thickness may correlate with activity of the lesion. The purpose of this study was to develop a method that can be used to automatically detect and measure the thickness of the transparent surface layer in PS-OCT images. Automated methods of analysis were used to measure the thickness of the transparent layer and the depth of the bovine enamel lesions produced using simulated caries models that emulate demineralization in the mouth. The transparent layer thickness measured with PS-OCT correlated well with polarization light microscopy (PLM) measurements of all regions (r2=0.9213). This study demonstrates that PS-OCT can automatically detect and measure thickness of the transparent layer formed due to remineralization in simulated caries lesions.

  8. Ion permeable microcapsules for the release of biologically available ions for remineralization.

    PubMed

    Davidson, Michael T; Greving, Theresa A; McHale, William A; Latta, Mark A; Gross, Stephen M

    2012-03-01

    The objective of this study was to investigate the effect of chemical structure, ion concentration, and ion type on the release rate of biologically available ions useful for remineralization from microcapsules with ion permeable membranes. A heterogeneous polymerization technique was utilized to prepare microcapsules containing either an aqueous solution of K₂HPO₄, Ca(NO₃)₂, or NaF. Six different polyurethane-based microcapsule shells were prepared and characterized based on ethylene glycol, butanediol, hexanediol, octanediol, triethylene glycol, and bisphenol A structural units. Ion release profiles were measured as a function of initial ion concentration within the microcapsule, ion type, and microcapsule chemical structure. The rate of ion release increased with initial concentration of ion stored in the microcapsule over a range of 0.5-3.0M. The monomer used in the synthesis of the membrane had a significant effect on ion release rates at 3.0 M salt concentration. At 1.0 M, the ethylene glycol released ions significantly faster than the hexanediol-, octanediol-, and butanediol-based microcapsules. Ion release was fastest for fluoride and slowest for phosphate for the salts used in this study. It was concluded that the microcapsules are capable of releasing calcium, phosphate, and fluoride ions in their biologically available form.

  9. Modeled diversity effects on microbial ecosystem functions of primary production, nutrient uptake, and remineralization.

    PubMed

    Goebel, Nicole L; Edwards, Christopher A; Follows, Michael J; Zehr, Jonathan P

    2014-01-01

    Ecosystem-wide primary productivity generally increases with primary producer diversity, emphasizing the importance of diversity for ecosystem function. However, most studies that demonstrate this positive relationship have focused on terrestrial and aquatic benthic systems, with little attention to the diverse marine pelagic primary producers that play an important role in regulating global climate. Here we show how phytoplankton biodiversity enhances overall marine ecosystem primary productivity and other ecosystem functions using a self-organizing ecosystem model. Diversity manipulation numerical experiments reveal positive, asymptotically saturating relationships between ecosystem-wide phytoplankton diversity and functions of productivity, nutrient uptake, remineralization, and diversity metrics used to identify mechanisms shaping these relationships. Increase in productivity with increasing diversity improves modeled ecosystem stability and model robustness and leads to productivity rates that exceed expected yields primarily through niche complementarity and facilitative interactions between coexisting phytoplankton types; the composition of traits in assemblages determines the magnitude of complementarity and selection effects. While findings based on these aggregate measures of diversity effects parallel those from the majority of experimental outcomes of terrestrial and benthic biodiversity-ecosystem function studies, we combine analyses of community diversity effects and investigations of the underlying interactions among phytoplankton types to demonstrate how an increase in recycled production of non-diatoms through an increase in new production of diatoms drives this diversity-cosystem function response. We demonstrate the important role that facilitation plays in the modeled marine plankton and how this facilitative interaction could amplify future climate-driven changes in ocean ecosystem productivity.

  10. Prophylactic antibiotic regimens in tumour surgery (PARITY)

    PubMed Central

    Investigators, The PARITY

    2015-01-01

    Objective Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. Methods We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. Results We screened 96 patients and enrolled 60 participants (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. Conclusions It is feasible to conduct a definitive multi-centre RCT of post-operative antibiotic regimens in patients with bone sarcomas, but further expansion of our collaborative network will be critical. We have demonstrated an ability to coordinate in multiple countries, enrol participants, maintain protocol adherence, and minimise losses to follow-up. Cite this article: Bone Joint Res;4:154–162 PMID:26423584

  11. AIRPOLISHING EFFECT ON BOVINE ENAMEL AND THE POSTERIOR REMINERALIZING EFFECT OF SALIVA. AN IN VITRO STUDY

    PubMed Central

    Ribeiro, Helena Zaramella Vono; Lima, José Eduardo de Oliveira; Vono, Bernardo Gonzalez; Machado, Maria Aparcida de Andrade Moreira; da Silva, Salete Moura Bonifácio

    2006-01-01

    Purpose: The aim of the present study was to evaluate the alterations of surface microhardness and wear caused by the sodium bicarbonate jet on bovine enamel and the further remineralizing effect of artificial saliva. Methods: Fifteen enamel samples (4,0mm × 4,0mm) were used, which constituted the groups: no treatment (MI); treatment with sodium bicarbonate jet (MII and DI); treatment with sodium bicarbonate jet and immersion in saliva for one hour (MIII and DII), 24 hours (MIV and DIII) and 7 days (MV and DIV). Microhardness tests were carried out using a microdurometer in groups M and wear tests by a rugosimeter in groups D. The data were assessed by the one criterion variance analysis and Tukey test. Results: The mean value of microhardness, in KHN, in groups MI, MII, MIII, MIV and MV were 359,80; 335,46; 369,20; 377,73 and 341,86, respectively, whereas the mean values in μm, of wear for group DI, DII, DIII and DIV were 0,564; 0,519; 0,441 and 0,428, respectively. Conclusions: The sodium bicarbonate jet caused a wear and a reduction in microhardness on the enamel surface; saliva promoted the recovery of initial condition surface microhardness and reduced the wear; the repairing effect of saliva on the surface microhardness alterations occurred within one hour of treatment, having no significant statistical difference from the effect obtained in 24 hours; the best saliva repairing effect on the wear occurred with treatment of 24 hours. PMID:19089072

  12. The effect of casein phosphopeptide toothpaste versus fluoride toothpaste on remineralization of primary teeth enamel.

    PubMed

    Yimcharoen, Veeritta; Rirattanapong, Praphasri; Kiatchallermwong, Warawan

    2011-07-01

    This study evaluated the effect of a CPP-containing toothpaste and compared it with fluoride-containing toothpastes on remineralization of caries-like lesions in primary teeth enamel, using polarized light microscopy. Forty-eight sound primary incisors were coated with nail varnish, leaving two 1x1 mm windows before being placed in a demineralizing solution for 4 days. After demineralization, all the specimens were coated with nail varnish over one window and were randomly assigned to 4 groups (A to D; n = 12). Group A teeth were exposed to distilled water. Group B teeth were exposed to a CPP-containing toothpaste (Hi Herb). Group C teeth were exposed to a 260 ppm fluoride-containing toothpaste (Smile baby toothgel). Group D teeth were exposed to a 500 ppm fluoride-containing toothpaste (Oralmed Kid). Polarized light microscopy was used to evaluate lesion depth, before and after a 7-day pH cycle. Lesion depth was measured using a computerized method with the Image-Pro Plus program. Differences in mean lesion depth within groups and between groups were analysed using the paired t-test, Kruskal-Wallis test and Mann-Whitney U test at a 95% level of confidence. Mean lesion depths in Groups A, B, C and D significantly increased by 110.1, 36.1, 40.2 and 18.2%, respectively. The mean lesion depths for all the toothpaste groups (B, C and D) were significantly different from the control group (A). Comparisons made among treatment groups showed Group D was significantly different from Groups B and C. All toothpastes were effective for inhibiting progression of carious lesions. However, a 500 ppm fluoride-containing toothpaste inhibited lesion progression better than a CPP-containing toothpaste and a 260 ppm fluoride-containing toothpaste.

  13. Dentine microhardness changes following conventional and alternate irrigation regimens: An in vitro study

    PubMed Central

    Das, Anusree; Kottoor, Jojo; Mathew, Joy; Kumar, Sanjana; George, Saira

    2014-01-01

    Aim: To compare the changes in microhardness of root dentin caused by two novel irrigation regimens with conventional irrigation. Materials and Methods: Forty extracted human permanent incisor teeth were selected. Decoronated roots were separated longitudinally to get 80 specimens that were embedded in autopolymerizing acrylic resin and grounded flat with silicon carbide abrasive papers. Of these, 60 root segments without any cracks or defects were selected and divided into four groups according to the irrigation regimen used (n = 15). Group I: 5% sodium hypochlorite (NaOCl) + 17% ethylenediaminetetraacetic acid (EDTA) + 0.2% chlorhexidine digluconate (CHX) (conventional). Group II: 6% Morinda Citrifolia Juice + 17% EDTA (MCJ). Group III: 5% NaOCl + Q Mix 2 in 1 (QMix). Group IV: Distilled water (control). Irrigation regimens were performed for 5 minutes. Dentin microhardness was measured with a Vickers indenter under a 200-g load and a 20-s dwell time at the midroot level of root dentin. The data were analyzed using Kruskal Wallis test and Dunn's multiple comparison tests. Results: A significant difference was seen in the median values of the four groups. The control group showed the least reduction in microhardness when comparison with the other groups. Except for Group III (Q Mix), the other groups that were tested (MCJ and conventional regimens) showed statistically significant difference from the control group. Conclusion: Within the limitation of this study, it was concluded that NaOCl + Q Mix were least detrimental to root dentin microhardness when compared with MCJ and conventional irrigation regimens. PMID:25506142

  14. Using ammonium pore water profiles to assess stoichiometry of deep remineralization processes in methanogenic continental margin sediments

    NASA Astrophysics Data System (ADS)

    Burdige, David J.; Komada, Tomoko

    2013-05-01

    many continental margin sediments, a deep reaction zone exists which is separated from remineralization processes near the sediment surface. Here, methane diffuses upward to a depth where it is oxidized by downwardly diffusing sulfate. However, the methane sources that drive this anaerobic oxidation of methane (AOM) in the sulfate-methane transition zone (SMT) may vary among sites. In particular, these sources can be thought of as either (i) "internal" sources from in situ methanogenesis (regardless of where it occurs in the sediment column) that are ultimately coupled to organic matter deposition and burial, or (ii) "external" sources such as hydrocarbon reservoirs derived from ancient source rocks, or deeply buried gas hydrates, both of which are decoupled from contemporaneous organic carbon deposition at the sediment surface. Using a modeling approach, we examine the relationship between different methane sources and pore water sulfate, methane, dissolved inorganic carbon (DIC), and ammonium profiles. We show that pore water ammonium profiles through the SMT represent an independent "tracer" of remineralization processes occurring in deep sediments that complement information obtained from profiles of solutes directly associated with AOM and carbonate precipitation, i.e., DIC, methane, and sulfate. Pore water DIC profiles also show an inflection point in the SMT based on the type of deep methane source and the presence/absence of accompanying upward DIC fluxes. With these results, we present a conceptual framework which illustrates how shallow pore water profiles from continental margin settings can be used to obtain important information about remineralization processes and methane sources in deep sediments.

  15. Reactive-transport modeling of iron diagenesis and associated organic carbon remineralization in a Florida (USA) subterranean estuary

    USGS Publications Warehouse

    Roy, Moutusi; Martin, Jonathan B.; Smith, Christopher G.; Cable, Jaye E.

    2011-01-01

    Iron oxides are important terminal electron acceptors for organic carbon (OC) remineralization in subterranean estuaries, particularly where oxygen and nitrate concentrations are low. In Indian River Lagoon, Florida, USA, terrestrial Fe-oxides dissolve at the seaward edge of the seepage face and flow upward into overlying marine sediments where they precipitate as Fe-sulfides. The dissolved Fe concentrations vary by over three orders of magnitude, but Fe-oxide dissolution rates are similar across the 25-m wide seepage face, averaging around 0.21 mg/cm2/yr. The constant dissolution rate, but differing concentrations, indicate Fe dissolution is controlled by a combination of increasing lability of dissolved organic carbon (DOC) and slower porewater flow velocities with distance offshore. In contrast, the average rate constants of Fe-sulfide precipitation decrease from 21.9 × 10-8 s-1 to 0.64 × 10-8 s-1 from the shoreline to the seaward edge of the seepage face as more oxygenated surface water circulates through the sediment. The amount of OC remineralized by Fe-oxides varies little across the seepage face, averaging 5.34 × 10-2 mg/cm2/yr. These rates suggest about 3.4 kg of marine DOC was remineralized in a 1-m wide, shore-perpendicular strip of the seepage face as the terrestrial sediments were transgressed over the past 280 years. During this time, about 10 times more marine solid organic carbon (SOC) accumulated in marine sediments than were removed from the underlying terrestrial sediments. Indian River Lagoon thus appears to be a net sink for marine OC.

  16. Non-destructive measurement of demineralization and remineralization in the occlusal pits and fissures of extracted 3rd molars with PS-OCT

    NASA Astrophysics Data System (ADS)

    Lee, Chulsung; Hsu, Dennis J.; Le, Michael H.; Darling, Cynthia L.; Fried, Daniel

    2009-02-01

    Previous studies have demonstrated that Polarization Sensitive Optical Coherence Tomography (PS-OCT) can be used to image the remineralization of early artificial caries lesion on smooth enamel surfaces of human and bovine teeth. However, most new dental decay is found in the pits and fissures of the occlusal surfaces of posterior dentition and it is in these high risk areas where the performance of new caries imaging devices need to be investigated. The purpose of this study was to demonstrate that PS-OCT can be used to measure the subsequent remineralization of artificial lesions produced in the pits and fissures of extracted 3rd molars. A PS-OCT system operating at 1310-nm was used to acquire polarization resolved images of occlusal surfaces exposed to a demineralizing solution at pH-4.5 followed by a fluoride containing remineralizing solution at pH-7.0 containing 2-ppm fluoride. The integrated reflectivity was calculated to a depth of 200-µm in the entire lesion area using an automated image processing algorithm. Although a well-defined surface zone was clearly resolved in only a few of the samples that underwent remineralization, the PS-OCT measurements indicated a significant (p<0.05) reduction in the integrated reflectivity between the severity of the lesions that were exposed to the remineralization solution and those that were not. The lesion depth and mineral loss were also measured with polarized light microscopy and transverse microradiography after sectioning the teeth. These results show that PS-OCT can be used to non-destructively monitor the remineralization potential of anti-caries agents in the important pits and fissures of the occlusal surface.

  17. Comparative study of the measurement of enamel demineralization and remineralization using transverse microradiography and electron probe microanalysis.

    PubMed

    Cochrane, Nathan J; Iijima, Youichi; Shen, Peiyan; Yuan, Yi; Walker, Glenn D; Reynolds, Coralie; MacRae, Colin M; Wilson, Nicholas C; Adams, Geoffrey G; Reynolds, Eric C

    2014-06-01

    Transverse microradiography (TMR) and electron probe microanalysis (EPMA) are commonly used for characterizing dental tissues. TMR utilizes an approximately monochromatic X-ray beam to determine the mass attenuation of the sample, which is converted to volume percent mineral (vol%min). An EPMA stimulates the emission of characteristic X-rays from a variable volume of sample (dependent on density) to provide compositional information. The aim of this study was to compare the assessment of sound, demineralized, and remineralized enamel using both techniques. Human enamel samples were demineralized and a part of each was subsequently remineralized. The same line profile through each demineralized lesion was analyzed using TMR and EPMA to determine vol%min and wt% elemental composition and atomic concentration ratio information, respectively. The vol%min and wt% values determined by each technique were significantly correlated but the absolute values were not similar. This was attributable to the complex ultrastructural composition, the variable density of the samples analyzed, and the nonlinear interaction of the EPMA-generated X-rays. EPMA remains an important technique for obtaining atomic ratio information, but its limitations in determining absolute mineral content indicate that it should not be used in place of TMR for determining the mineral density of dental hard tissues.

  18. In vitro study of remineralization of dentin: effects of ions on mineral induction by decalcified dentin matrix.

    PubMed

    Saito, Takashi; Toyooka, Hiroki; Ito, Shuichi; Crenshaw, Miles A

    2003-01-01

    We examined the effects of various ions on the mineralization of dentin matrix in vitro. Demineralized dentin matrix was incubated in a metastable calcium phosphate solution with or without silicate, fluoride, calcium, phosphate, magnesium or silver. Insoluble dentin matrix induced mineral formation after incubation for 10.2 h in the metastable solution without added ions. Silicate at 5 microM and fluoride at 40 microM significantly reduced the mineral induction time. At least 200 microM calcium or 100 microM phosphate was required to promote mineral induction. Conversely, magnesium and silver concentrations as low as 10 and 2 microM inhibited mineral induction. The mineral induced by each sample after incubation for 24 h was identified by its X-ray diffraction pattern as apatite. We concluded that silicate is a stronger inducer of remineralization of dentin matrix than fluoride, calcium or phosphate, and that magnesium and silver inhibit the induction of remineralization of dentin matrix.

  19. In situ protocol for the determination of dose-response effect of low-fluoride dentifrices on enamel remineralization

    PubMed Central

    AFONSO, Rebeca Lima; PESSAN, Juliano Pelim; IGREJA, Bruna Babler; CANTAGALLO, Camila Fernandes; DANELON, Marcelle; DELBEM, Alberto Carlos Botazzo

    2013-01-01

    No in situ protocol has assessed the dose-response effects of fluoride dentifrices involving low-fluoride formulations. Objective To assess the ability of an in situ remineralization model in determining dose-response effects of dentifrices containing low fluoride concentrations ([F]) on bovine enamel. Material and Methods Volunteers wore palatal appliances containing demineralized enamel blocks and brushed their teeth and devices with the dentifrices supplied (double-blind, crossover protocol) separately for 3 and 7 days. Surface hardness (SH), integrated subsurface hardness (ΔKHN) and [F] in enamel were determined. Data were analyzed by ANOVA, Tukey's test and Pearson's correlation (p<0.05). Results Dose-response relationships were verified between [F] in dentifrices and SH, ΔKHN and enamel [F]. Higher correlation coefficients between enamel [F] and SH and ΔKHN were obtained for the 3-day period. Significant differences in SH and ΔKHN were observed among all groups for the 3-day period, but not between 0-275, 275-550, and 550-1,100 µg F/g dentifrices for the 7-day period, nor between 3- and 7-day periods for the 1,100 µg F/g groups. Conclusions Considering that the peak remineralization capacity of the conventional dentifrice (1,100 µg F/g) was achieved in 3 days, this experimental period could be used in future studies assessing new dentifrice formulations, especially at low-fluoride concentrations. PMID:24473718

  20. Efficacy of Concomitant Therapy with Fluoride and Chlorhexidine Varnish on Remineralization of Incipient Lesions in Young Children

    PubMed Central

    Tandon, Shobha; Nayak, Rashmi; Ratnanag, P Venkat; Prajapati, Deepesh; Kamath, Namitha

    2016-01-01

    Aim To assess the effect of combined use of chlorhexidine and fluoride varnish on the remineralization of incipient carious lesions in young children. Materials and methods Twenty caries-active children (80 lesions) were randomly divided into four groups and subjected to initial examination. Caries status was assessed visually and with the aid of DIAGNOdent. Baseline enamel biopsies were obtained. Subjects of groups I and II received fluoride and chlorhexidine varnish respectively. Group III received both fluoride and chlorhexidine varnish alternatively, for a period of 4 weeks. Group IV served as the control. At 3-month follow-up, the incipient lesions were assessed again with DIAGNOdent and enamel biopsy. Results Increased calcium, phosphate, and fluoride levels were noticed in groups I, II, III compared to group IV, at the 3-month follow-up (p < 0.001). Conclusion The combined therapy with fluoride and chlorhex-idine varnish may be considered an alternative therapy for early reversal of incipient lesions. How to cite this article Naidu S, Tandon S, Nayak R, Ratnanag PV, Prajapati D, Kamath N. Efficacy of Concomitant Therapy with Fluoride and Chlorhexidine Varnish on Remineralization of Incipient Lesions in Young Children. Int J Clin Pediatr Dent 2016;9(4):296-302. PMID:28127159

  1. A Comparison of Breast Cancer Treatment Regimens by Demographic Characteristics

    DTIC Science & Technology

    1998-10-01

    Cancer Treatment Regimens by Demographic Characteristics PRINCIPAL INVESTIGATOR: Marianne E. Ulcickas Yood, M.P.H. CONTRACTING ORGANIZATION: Henry...NUMBERS A Comparison of Breast Cancer Treatment Regimens by Demographic Characteristics DAMD17-97-1-7302 6. AUTHOR(S) Marianne E. Ulcickas Yood, M.P.H. 7... Cancer Treatment Regimens by Demographic Characteristics (DAMD17-97-1-7302), Annual Report October, 1998 TABLE OF CONTENTS Introduction

  2. Prevalence of inappropriate tuberculosis treatment regimens: a systematic review

    PubMed Central

    Langendam, M.W.; van der Werf, M.J.; Huitric, E.; Manissero, D.

    2012-01-01

    A potential threat to the success of new tuberculosis (TB) drugs is the development of resistance. Using drugs in appropriate regimens, such as those recommended in the World Health Organization (WHO) treatment guidelines, prevents the development of resistance. We performed a systematic review to assess the prevalence of inappropriate prescription of TB drugs for the treatment of TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Observational studies published from 2000 that included TB patients receiving treatment were selected. A treatment regimen was considered inappropriate if the regimen was not a WHO recommended regimen. 37 studies were included. Inappropriate treatment regimens were prescribed in 67% of studies. The percentage of patients receiving inappropriate regimens varied between 0.4% and 100%. In 19 studies the quality of treatment regimen reporting was low. Despite the fact that assessment of inappropriate treatment was hampered by low quality of reporting, our data indicate a reasonable amount of inappropriate prescription of TB treatment regimens. Thus, there is a risk that new drugs will be used in inappropriate treatment regimens, even with WHO guidelines in place, introducing the risk of resistance development. This article highlights the need to improve implementation of the WHO treatment of TB guidelines. PMID:22005923

  3. Geochemical ecosystem engineering by the mud shrimp Upogebia pugettensis (Crustacea: Thalassinidae) in Yaquina Bay, Oregon: density-dependent effects on organic matter remineralization and nutrient cycling

    EPA Science Inventory

    We investigated the effect of the thalassinid mud shrimp Upogebia pugettensis on organic matter and nutrient cycling on Idaho Flat, an intertidal flat in the Yaquina River estuary, Oregon. Field studies were conducted to measure carbon and nitrogen remineralization rates and bent...

  4. A Polarized Light Microscopic Study to Comparatively evaluate Four Remineralizing Agents on Enamel viz CPP-ACPF, ReminPro, SHY-NM and Colgate Strong Teeth

    PubMed Central

    Krishnan, Ramesh; Bhaskaran, Bibin; Kumar, Suresh V

    2015-01-01

    ABSTRACT Aim: To compare and evaluate the remineralizing potential of four commercially available products namely SHY-NM, GC Tooth Mousse Plus, ReminPro and Colgate strong teeth on demineralized human teeth. Materials and methods: The study included 50 extracted premolars having 3 × 3 mm window prepared on the middle third of the tooth, which was then subjected to demineralization for 48 hours at 37°C. Teeth were randomly selected and grouped into five study groups of 10 teeth in each. Each group was treated with respective remineralizing agent and sectioned using hard-tissue microtome. Each section obtained was visualized under polarized light microscope and analyzed using Image J software. Results: The statistically evaluated results revealed that SHY-NM has the most remineralizing potential followed by ReminPro, GC Tooth Mousse Plus and fluoridated toothpaste. Conclusion: Based on the study, the SHY-NM was superior to the GC Tooth Mousse Plus, ReminPro and Colgate strong teeth on demineralized human teeth. How to cite this article: Rajan R, Krishnan R, Bhaskaran B, Kumar SV. A Polarized Light Microscopic Study to Comparatively evaluate Four Remineralizing Agents on Enamel viz CPP-ACPF, ReminPro, SHY-NM and Colgate Strong Teeth. Int J Clin Pediatr Dent 2015;8(1):42-47. PMID:26124580

  5. Barium in Twilight Zone suspended matter as a potential proxy for particulate organic carbon remineralization: Results for the North Pacific

    SciTech Connect

    Dehairs, F.; Jacquet, S.; Savoye, N.; Van Mooy, B.A.S.; Buesseler, K.; Bishop, J.K.B.; Lamborg, C.H.; Elskens, M.; Baeyens, W.; Boyd, P.W.; Casciotti, K.L.; Monnin, C.

    2008-04-10

    This study focuses on the fate of exported organic carbon in the twilight zone at two contrasting environments in the North Pacific: the oligotrophic ALOHA site (22 degrees 45 minutes N 158 degrees W; Hawaii; studied during June-July 2004) and the mesotrophic Subarctic Pacific K2 site (47 degrees N, 161 degrees W; studied during July-August 2005). Earlier work has shown that non-lithogenic, excess particulate Ba (Ba{sub xs}) in the mesopelagic water column is a potential proxy of organic carbon remineralization. In general Ba{sub xs} contents were significantly larger at K2 than at ALOHA. At ALOHA the Ba{sub xs} profiles from repeated sampling (5 casts) showed remarkable consistency over a period of three weeks, suggesting that the system was close to being at steady state. In contrast, more variability was observed at K2 (6 casts sampled) reflecting the more dynamic physical and biological conditions prevailing in this environment. While for both sites Ba{sub xs} concentrations increased with depth, at K2 a clear maximum was present between the base of the mixed layer at around 50m and 500m, reflecting production and release of Ba{sub xs}. Larger mesopelagic Ba{sub xs} contents and larger bacterial production in the twilight zone at the K2 site indicate that more material was exported from the upper mixed layer for bacterial degradation deeper, compared to the ALOHA site. Furthermore, application of a published transfer function (Dehairs et al., 1997) relating oxygen consumption to the observed Ba{sub xs} data indicated that the latter were in good agreement with bacterial respiration, calculated from bacterial production. These results corroborate earlier findings highlighting the potential of Ba{sub xs} as a proxy for organic carbon remineralization. The range of POC remineralization rates calculated from twilight zone excess particulate Ba contents did also compare well with the depth dependent POC flux decrease as recorded by neutrally buoyant sediment traps

  6. PROPOSAL OF ANTI-TUBERCULOSIS REGIMENS BASED ON SUSCEPTIBILITY TO ISONIAZID AND RIFAMPICIN

    PubMed Central

    Mendoza-Ticona, Alberto; Moore, David AJ; Alarcón, Valentina; Samalvides, Frine; Seas, Carlos

    2014-01-01

    Objective To elaborate optimal anti-tuberculosis regimens following drug susceptibility testing (DST) to isoniazid (H) and rifampicin (R). Design 12 311 M. tuberculosis strains (National Health Institute of Peru 2007-2009) were classified in four groups according H and R resistance. In each group the sensitivity to ethambutol (E), pirazinamide (Z), streptomycin (S), kanamycin (Km), capreomycin (Cm), ciprofloxacin (Cfx), ethionamide (Eto), cicloserine (Cs) and p-amino salicilic acid (PAS) was determined. Based on resistance profiles, domestic costs, and following WHO guidelines, we elaborated and selected optimal putative regimens for each group. The potential efficacy (PE) variable was defined as the proportion of strains sensitive to at least three or four drugs for each regimen evaluated. Results Selected regimes with the lowest cost, and highest PE of containing 3 and 4 effective drugs for TB sensitive to H and R were: HRZ (99,5%) and HREZ (99,1%), respectively; RZECfx (PE=98,9%) and RZECfxKm (PE=97,7%) for TB resistant to H; HZECfx (96,8%) and HZECfxKm (95,4%) for TB resistant to R; and EZCfxKmEtoCs (82.9%) for MDR-TB. Conclusion Based on resistance to H and R it was possible to select anti-tuberculosis regimens with high probability of success. This proposal is a feasible alternative to tackle tuberculosis in Peru where the access to rapid DST to H and R is improving progressively. PMID:23949502

  7. Enhancing Commitment Improves Adherence to a Medical Regimen.

    ERIC Educational Resources Information Center

    Putnam, Dana E.; And Others

    1994-01-01

    Evaluated commitment-based intervention for improvement of adherence to 10-day antibiotic regimen. Subjects were 60 college students. Experimental subjects made verbal and written commitments for adherence and completed tasks designed to increase their investment in medication regimen. Controls performed similarly structured tasks unrelated to…

  8. The role of zooplankton in the cycling and remineralization of chemical materials in the Southern California Bight

    SciTech Connect

    Small, L.F.; Huh, Chih-An.

    1988-01-01

    The overall objective of our research is to understand the transport pathways and mass balances of selected metabolically active and inactive chemical species in the Santa Monica/San Pedro Basins. One focus of our study is to examine the role of zooplankton and micronekton in the cycling and remineralization of chemical materials in the Southern California Bight, with particular reference to C, N and certain radionuclides and trace metals. A second focus is to examine these same radionuclides and trace metals in other important reservoirs. Knowledge of the rates and routes of transfer of these nuclides and metals through these reservoirs should lead to a cogent model for these elements in SM/SP Basins. Our zooplankton C and N data, should lead ultimately to a model of C and N cycling in the upper water column. Our sediment core data will lead to the construction of mass balances and budgets in the SM/SP Basins. 4 refs.

  9. Individualizing phenytoin dosage regimens using a programmable calculator.

    PubMed

    Ng, P K

    1980-04-01

    A programmable calculator procedure for the determination of individualized phenytoin dosage regimens is described. The calculator is programmed based on a one-compartment, open model using the Michaelis-Menten equation. A detailed description of the programs and user instructions are presented. The programs allow calculation of oral dosage regimens and steady-state phenytoin levels. The first two programs require a given dose and one corresponding steady-state minimum concentration point to estimate a dosage regimen and steady-state serum level. The second two programs, which provide a more accurate prediction of dosage regimen and steady-state serum levels, require two dose and steady-state minimum concentration poits. The calculator programs provide a rapid and reliable means of estimating a patient's phenytoin dosage regimens and steady-state serum levels.

  10. Remineralization of demineralized bone matrix in critical size cranial defects in rats: A 6-month follow-up study.

    PubMed

    Horváthy, Dénes B; Vácz, Gabriella; Toró, Ildikó; Szabó, Tamás; May, Zoltán; Duarte, Miguel; Hornyák, István; Szabó, Bence T; Dobó-Nagy, Csaba; Doros, Attila; Lacza, Zsombor

    2016-10-01

    The key drawback of using demineralized bone matrix (DBM) is its low initial mechanical stability due to the severe depletion of mineral content. In the present study, we investigated the long-term regeneration of DBM in a critical size bone defect model and investigated the remineralization after 6 months. Bone defects were created in the cranium of male Wistar rats which were filled with DBM or left empty as negative control. In vivo bone formation was monitored with computed tomography after 11, 19, and 26 weeks postoperatively. After 6 months, parietal bones were subjected to micro-CT. Mineral content was determined with spectrophotometric analysis. After 11 weeks the DBM-filled bone defects were completely closed, while empty defects were still open. Density of the DBM-treated group increased significantly while the controls remained unchanged. Quantitative analysis by micro-CT confirmed the in vivo results, bone volume/tissue volume was significantly lower in the controls than in the DBM group. The demineralization procedure depleted the key minerals of the bone to a very low level. Six months after implantation Ca, P, Na, Mg, Zn, and Cr contents were completely restored to the normal level, while K, Sr, and Mn were only partially restored. The remineralization process of DBM is largely complete by the 6th month after implantation in terms of bone density, structure, and key mineral levels. Although DBM does not provide sufficient sources for any of these minerals, it induces a faster and more complete regeneration process. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1336-1342, 2016.

  11. Influence of nutrient utilization and remineralization stoichiometry on phytoplankton species and carbon export: A modeling study at BATS

    NASA Astrophysics Data System (ADS)

    Salihoglu, B.; Garçon, V.; Oschlies, A.; Lomas, M. W.

    2008-01-01

    The primary objective of this research is to understand the underlying mechanisms of the time-varying flux of carbon in the Sargasso Sea. To address this objective, a one-dimensional multi-component lower trophic level ecosystem model that includes detailed algal physiology as well as nutrient cycles is used at the Bermuda Atlantic Time-series Study (BATS, 31∘40'N, 64∘10'W) site. In this model autotrophic growth is represented by three algal groups and the cell quota approach is used to estimate algal growth and nutrient uptake. This model is tested and evaluated for year 1998 using the bimonthly BATS cruise data. Results show that phosphorus and dissolved organic matter (DOM) are necessary compartments to correctly simulate organic elemental cycles at the BATS site. Model results show that autotrophic eukaryotes and cyanobacteria (i.e. Prochlorococcus and Synechococcus) are the most abundant algal groups and are responsible for 63% and 33% of carbon production in the region, respectively. Sensitivity analyses show that the annual contribution of nitrogen fixation and atmospheric nitrogen deposition to new production is approximately 9% and 3%, respectively. However, the recycled nitrogen and phosphorus are important components of the ecosystem dynamics because sustained growth of algal groups depends on remineralized nutrients which accounts for 75% of the annual carbon production. Nutrient uptake and remineralization stoichiometry can play an important role in determining the surface ocean nutrient distribution. Model results suggest phosphate limitation even during the spring bloom. Phosphate may thus limit the growth of all algal groups throughout the year.

  12. In silico evaluation and exploration of antibiotic tuberculosis treatment regimens

    DOE PAGES

    Pienaar, Elsje; Dartois, Véronique; Linderman, Jennifer J.; ...

    2015-11-14

    Improvement in tuberculosis treatment regimens requires selection of antibiotics and dosing schedules from a large design space of possibilities. Incomplete knowledge of antibiotic and host immune dynamics in tuberculosis granulomas impacts clinical trial design and success, and variations among clinical trials hamper side-by-side comparison of regimens. Our objective is to systematically evaluate the efficacy of isoniazid and rifampin regimens, and identify modifications to these antibiotics that improve treatment outcomes. We pair a spatio-temporal computational model of host immunity with pharmacokinetic and pharmacodynamic data on isoniazid and rifampin. The model is calibrated to plasma pharmacokinetic and granuloma bacterial load data frommore » non-human primate models of tuberculosis and to tissue and granuloma measurements of isoniazid and rifampin in rabbit granulomas. We predict the efficacy of regimens containing different doses and frequencies of isoniazid and rifampin. We predict impacts of pharmacokinetic/pharmacodynamic modifications on antibiotic efficacy. We demonstrate that suboptimal antibiotic concentrations within granulomas lead to poor performance of intermittent regimens compared to daily regimens. Improvements from dose and frequency changes are limited by inherent antibiotic properties, and we propose that changes in intracellular accumulation ratios and antimicrobial activity would lead to the most significant improvements in treatment outcomes. Results suggest that an increased risk of drug resistance in fully intermittent as compared to daily regimens arises from higher bacterial population levels early during treatment. In conclusion, our systems pharmacology approach complements efforts to accelerate tuberculosis therapeutic development.« less

  13. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Cancer.gov

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  14. Gonzalez Regimen (PDQ®)—Health Professional Version

    Cancer.gov

    Expert-reviewed information summary about the Gonzalez regimen as a treatment for people with cancer. Note: The information in this summary is no longer being updated and is provided for reference purposes only.

  15. What to Start: Selecting a First HIV Regimen

    MedlinePlus

    ... medicines to treat HIV infection is called antiretroviral therapy (ART). People on ART take a combination of HIV ... treat HIV infection. HIV treatment (also called antiretroviral therapy or ART) begins with choosing an HIV regimen. People on ...

  16. Preferential remineralization of dissolved organic phosphorus and non-Redfield DOM dynamics in the global ocean: Impacts on marine productivity, nitrogen fixation, and carbon export

    NASA Astrophysics Data System (ADS)

    Letscher, Robert T.; Moore, J. Keith

    2015-03-01

    Selective removal of nitrogen (N) and phosphorus (P) from the marine dissolved organic matter (DOM) pool has been reported in several regional studies. Because DOM is an important advective/mixing pathway of carbon (C) export from the ocean surface layer and its non-Redfieldian stoichiometry would affect estimates of marine export production per unit N and P, we investigated the stoichiometry of marine DOM and its remineralization globally using a compiled DOM data set. Marine DOM is enriched in C and N compared to Redfield stoichiometry, averaging 317:39:1 and 810:48:1 for C:N:P within the degradable and total bulk pools, respectively. Dissolved organic phosphorus (DOP) is found to be preferentially remineralized about twice as rapidly with respect to the enriched C:N stoichiometry of marine DOM. Biogeochemical simulations with the Biogeochemical Elemental Cycling model using Redfield and variable DOM stoichiometry corroborate the need for non-Redfield dynamics to match the observed DOM stoichiometry. From our model simulations, preferential DOP remineralization is found to increase the strength of the biological pump by ~9% versus the case of Redfield DOM cycling. Global net primary productivity increases ~10% including an increase in marine nitrogen fixation of ~26% when preferential DOP remineralization and direct utilization of DOP by phytoplankton are included. The largest increases in marine nitrogen fixation, net primary productivity, and carbon export are observed within the western subtropical gyres, suggesting the lateral transfer of P in the form of DOP from the productive eastern and poleward gyre margins may be important for sustaining these processes downstream in the subtropical gyres.

  17. Moving East: the Euro-Lupus Nephritis regimen in Asia.

    PubMed

    Houssiau, Frédéric A

    2016-01-01

    Treatment of lupus nephritis is more evidenced-based than ever. Yet many areas of uncertainty persist. The article by Rathi et al. brings a piece to the puzzle by comparing, in a group of Indian patients, the Euro-Lupus low-dose i.v. cyclophosphamide regimen with mycophenolate mofetil. Although some caveats must be raised, the results suggest that, after crossing the Atlantic, the Euro-Lupus regimen may well be moving East.

  18. [Principles of organizing efficient work and rest regimens for crews on prolonged space flights].

    PubMed

    Litsov, A N; Bulyko, V I

    1983-01-01

    The work-rest cycles of Salyut-6 crews were investigated. Several modifications were detected: 24-hour static regimens (65-70%) and altered regimens (35-30%) with longer or shorter work-rest cycles. It is concluded that in prolonged space flights two regimens are allowed: principal regimens (normal static regimens of work and rest) used throughout the flight, and operational regimens (differing from 24-hour ones) used no more than once every 7-10 days.

  19. Novel calcium infusion regimen after parathyroidectomy for renal hyperparathyroidism

    PubMed Central

    Tan, Jih Huei; Tan, Henry Chor Lip; Arulanantham, Sarojah A/P

    2017-01-01

    Abstract Aim Calcium infusion is used after parathyroid surgery for renal hyperparathyroidism to treat postoperative hypocalcaemia. We compared a new infusion regimen to one commonly used in Malaysia based on 2003 K/DOQI guidelines. Methods Retrospective data on serum calcium and infusion rates was collected from 2011–2015. The relationship between peak calcium efflux (PER) and time was determined using a scatterplot and linear regression. A comparison between regimens was made based on treatment efficacy (hypocalcaemia duration, total infusion amount and time) and calcium excursions (outside target range, peak and trough calcium) using bar charts and an unpaired t‐test. Results Fifty‐one and 34 patients on the original and new regimens respectively were included. Mean PER was lower (2.16 vs 2.56 mmol/h; P = 0.03) and occurred earlier (17.6 vs 23.2 h; P = 0.13) for the new regimen. Both scatterplot and regression showed a large correlation between PER and time (R‐square 0.64, SE 1.53, P < 0.001). The new regimen had shorter period of hypocalcaemia (28.9 vs 66.4 h, P = 0.04), and required less calcium infusion (67.7 vs 127.2 mmol, P = 0.02) for a shorter duration (57.3 vs 102.9 h, P = 0.001). Calcium excursions, peak and trough calcium were not significantly different between regimens. Early postoperative high excursions occurred when the infusion was started in spite of elevated peri‐operative calcium levels. Conclusion The new infusion regimen was superior to the original in that it required a shorter treatment period and resulted in less hypocalcaemia. We found that early aggressive calcium replacement is unnecessary and raises the risk of rebound hypercalcemia. PMID:26952689

  20. BK virus replication following kidney transplant: does the choice of immunosuppressive regimen influence outcomes?

    PubMed

    Acott, Phillip; Babel, Nina

    2012-01-01

    The increasing prevalence of BK virus nephropathy (BKVN) observed in recent years, with its consequent impact on kidney allograft survival rates, has focused attention on the relationship between immunosuppression regimens and risk of BK virus reactivation. The adoption of more potent immunosuppressive regimens over the last two decades, notably tacrolimus with mycophenolic acid and corticosteroids, appears to be associated with higher rates of BK activation. There is also evidence of a specific increase in risk for tacrolimus-based immunosuppression vs. cyclosporine, which in vitro data suggest may be at least partly due to differences in antiviral activity. Early concerns that mammalian target of rapamycin (mTOR) inhibitor use was associated with development of BKVN do not appear to have been borne out. Protocol-driven BK virus screening is recommended to facilitate early diagnosis and intervention, which primarily comprises the controlled reduction or discontinuation of immunosuppressive drugs. Although a consensus on the optimal strategy for immunosuppression modification is still lacking, early diagnosis of BK reactivation and pre-emptive modification of immunosuppression has resulted in a marked improvement in graft outcomes. Typically, intervention consists of reducing calcineurin inhibitor exposure before or after antimetabolite dose reduction, withdrawal of one agent from a triple therapy regimen, or switching between agents within a therapeutic class. A benefit for antiviral therapy is not yet confirmed. While more data are required, the current evidence base is adequate to justify routine screening with early modification of the intensity and nature of the immunosuppression regimen to reduce the toll of BKVN in the kidney transplant population.

  1. Electron probe micro-analysis for subsurface demineralization and remineralization of dental enamel

    SciTech Connect

    Chu, J.S.; Fox, J.L.; Higuchi, W.I.; Nash, W.P.

    1989-01-01

    A quantitative study of fluoride distribution profile changes in dental enamel was conducted by means of electron probe micro-analysis (EPMA). Fluoride-deposited hydroxyapatite powders were chosen as fluoride standards, and analytical conditions were optimized. The lower limit of detection for fluoride was estimated to be 270 ppm, with an accelerating voltage of 5 kV, a specimen current of 40 nA, and a counting time of 40 seconds. Fluoride profiles in fluoride-treated dental enamel, which exhibited intact surface layers and subsurface demineralization, were determined. The results were also compared with those of an acid-abrasion method, and reasonable consistency was found between these two methods, although the acid-abrasion procedure yielded a slightly lower fluoride content in the initial layers, followed by a higher content of fluoride in the deeper layers. The precision of fluoride profile data obtained from EPMA permits further studies to be conducted on the kinetics of subsurface demineralization and intact surface layer formation (white spot formation) which is observed during the acid challenge of dental enamel.

  2. Development of antibiotic regimens using graph based evolutionary algorithms.

    PubMed

    Corns, Steven M; Ashlock, Daniel A; Bryden, Kenneth M

    2013-12-01

    This paper examines the use of evolutionary algorithms in the development of antibiotic regimens given to production animals. A model is constructed that combines the lifespan of the animal and the bacteria living in the animal's gastro-intestinal tract from the early finishing stage until the animal reaches market weight. This model is used as the fitness evaluation for a set of graph based evolutionary algorithms to assess the impact of diversity control on the evolving antibiotic regimens. The graph based evolutionary algorithms have two objectives: to find an antibiotic treatment regimen that maintains the weight gain and health benefits of antibiotic use and to reduce the risk of spreading antibiotic resistant bacteria. This study examines different regimens of tylosin phosphate use on bacteria populations divided into Gram positive and Gram negative types, with a focus on Campylobacter spp. Treatment regimens were found that provided decreased antibiotic resistance relative to conventional methods while providing nearly the same benefits as conventional antibiotic regimes. By using a graph to control the information flow in the evolutionary algorithm, a variety of solutions along the Pareto front can be found automatically for this and other multi-objective problems.

  3. Design of initial dosage regimen using a programmable calculator.

    PubMed

    Ritschel, W A; Eldon, M A

    1985-07-01

    A programmable calculator procedure for the determination of dosage regimens to achieve desired steady state concentrations is described. The dosage regimen prediction is based on data from the literature on pharmacokinetic parameters of drugs and correction factors specific for the patient's condition, such as renal failure, geriatric patient and congestive heart failure. The program is designed to generate dosage regimens based on desired steady state trough level, desired steady state peak level, desired mean steady state level, or to fluctuate between desired steady state peak and trough levels. The program can be used for I.V. and extravascular route of administration. A detailed program description and user instructions are presented and illustrated by three examples.

  4. Principles for designing future regimens for multidrug-resistant tuberculosis.

    PubMed

    Brigden, Grania; Nyang'wa, Bern-Thomas; du Cros, Philipp; Varaine, Francis; Hughes, Jennifer; Rich, Michael; Horsburgh, C Robert; Mitnick, Carole D; Nuermberger, Eric; McIlleron, Helen; Phillips, Patrick P J; Balasegaram, Manica

    2014-01-01

    Fewer than 20% of patients with multidrug-resistant (MDR) tuberculosis are receiving treatment and there is an urgent need to scale up treatment programmes. One of the biggest barriers to scale-up is the treatment regimen, which is lengthy, complex, ineffective, poorly tolerated and expensive. For the first time in over 50 years, new drugs have been developed specifically to treat tuberculosis, with bedaquiline and potentially delamanid expected to be available soon for treatment of MDR cases. However, if the new drugs are merely added to the current treatment regimen, the new regimen will be at least as lengthy, cumbersome and toxic as the existing one. There is an urgent need for strategy and evidence on how to maximize the potential of the new drugs to improve outcomes and shorten treatment. We devised eight key principles for designing future treatment regimens to ensure that, once they are proven safe in clinical trials, they will be clinically effective and programmatically practicable. Regimens should contain at least one new class of drug; be broadly applicable for use against MDR and extensively drug-resistant Mycobacterium tuberculosis complex strains; contain three to five effective drugs, each from a different drug class; be delivered orally; have a simple dosing schedule; have a good side-effect profile that allows limited monitoring; last a maximum of 6 months; and have minimal interaction with antiretrovirals. Following these principles will maximize the potential of new compounds and help to overcome the clinical and programmatic disadvantages and scale-up constraints that plague the current regimen.

  5. Adjuvant, neoadjuvant, and experimental regimens in overcoming pancreatic ductal adenocarcinoma

    PubMed Central

    Wysocka, Olga; Kulbacka, Julita; Saczko, Jolanta

    2016-01-01

    Pancreatic cancer is one of the most aggressive and deadly malignancies. Despite better understanding of its biology and pathogenesis, contemporary treatment regimens are still insufficient. Along with the introduction of new treatment agents and combination therapy, the response rates are increasing, but these scores do not go with overall survival, and results are frequently conflicting. Therefore, contemporary medicine faces the challenge of expanding the knowledge base and practice on all grounds – pathology, factor risk, diagnosis, and finally surgical and palliative treatment of this disease. This paper provides a review of current adjuvant and neoadjuvant regimens and the role of experimental therapies in pancreatic ductal adenocarcinoma. PMID:27713776

  6. Hepatitis C Virus Infection: Looking for Interferon Free Regimens

    PubMed Central

    González-Moreno, J.; Payeras-Cifre, A.

    2013-01-01

    Recent developments of new drugs' combinations are changing the treatment paradigm in hepatitis C virus infection. Due to the side effect profile of pegylated interferons, interferon-sparing regimens have become the main target in chronic hepatitis C treatment research. Recent proofs of concept studies have suggested that cure of chronic hepatitis C can be achieved without interferon. The purpose of this paper is to provide an overview of the clinical results recently reported for the treatment of hepatitis C virus infection with interferon-free regimens, focusing on the most promising new compounds and combinations. PMID:23710151

  7. Zagreb Regimen, an Abbreviated Intramuscular Schedule for Rabies Vaccination

    PubMed Central

    Ren, Jiangping; Yao, Linong; Sun, Jimin

    2014-01-01

    The Zagreb regimen, an abbreviated intramuscular schedule for rabies vaccination, was developed by I. Vodopija and colleagues of the Zagreb Institute of Public Health in Croatia in the 1980s. It was recommended by WHO as one of the intramuscular (IM) schedules for rabies vaccination in 2010. We reviewed the literature on the immunogenicity, safety, economic burden, and compliance of the Zagreb 2-1-1 regimen. Compared to Essen, another IM schedule recommended by WHO, Zagreb has higher compliance, lower medical cost, and better immunogenicity at an early stage. PMID:25392012

  8. In Situ Investigation of the Remineralizing Effect of Saliva and Fluoride on Enamel Following Prophylaxis Using Sodium Bicarbonate

    PubMed Central

    Grazziotin, Gladis Benjamina; Rios, Daniela; Honório, Heitor Marques; Silva, Salete Moura Bonifácio; Lima, José Eduardo Oliveira

    2011-01-01

    Objectives: This in situ study evaluated the effect of saliva, associated or not with fluoride, on enamel previously submitted to prophylaxis using sodium bicarbonate. Methods: The study was conducted on enamel blocks submitted to in vitro prophylaxis using sodium bicarbonate. The blocks were randomly divided into 2 groups (G1/G2) and mounted on intraoral appliances wore by 10 volunteers. G1 blocks were directly exposed to saliva in situ, while blocks in G2 were exposed to saliva with fluoride (rinsing with 0.2% NaF solution during the initial minute). Enamel alterations were evaluated using surface microhardness and profilometry. Enamel hardness data were analyzed by ANOVA and Tukey tests and surface wear was evaluated using paired t test (P<.05). Results: No significant differences were found between G1 and G2 for enamel hardness and wear. The wear after prophylaxis was not different from the wear after the in situ stage. Baseline mean values of enamel hardness, after prophylaxis and after the in situ stage were 340±16.6, 329±35.7 and 354±37.8 for G1 and 338±15.6, 312±46.3 and 340±21.8 for G2, respectively. Conclusions: It was concluded that saliva alone exhibited a similar effect to saliva associated with fluoride; after 4h of in situ remineralization, there was no recovery in height of the enamel structure that had been lost due to the application of sodium bicarbonate. PMID:21228955

  9. Variations of iron flux and organic carbon remineralization in a subterranean estuary caused by interannual variations in recharge

    USGS Publications Warehouse

    Roy, Moutusi; Martin, Jonathan B.; Cable, Jaye E.; Smith, Christopher G.

    2013-01-01

    We determine the inter-annual variations in diagenetic reaction rates of sedimentary iron (Fe ) in an east Florida subterranean estuary and evaluate the connection between metal fluxes and recharge to the coastal aquifer. Over the three-year study period (from 2004 to 2007), the amount of Fe-oxides reduced at the study site decreased from 192 g/yr to 153 g/yr and associated organic carbon (OC) remineralization decreased from 48 g/yr to 38 g/yr. These reductions occurred although the Fe-oxide reduction rates remained constant around 1 mg/cm2/yr. These results suggest that changes in flow rates of submarine groundwater discharge (SGD) related to changes in precipitation may be important to fluxes of the diagenetic reaction products. Rainfall at a weather station approximately 5 km from the field area decreased from 12.6 cm/month to 8.4 cm/month from 2004 to 2007. Monthly potential evapotranspiration (PET) calculated from Thornthwaite’s method indicated potential evapotranspiration cycled from about 3 cm/month in the winter to about 15 cm/month in the summer so that net annual recharge to the aquifer decreased from 40 cm in 2004 to -10 cm in 2007. Simultaneously, with the decrease in recharge of groundwater, freshwater SGD decreased by around 20% and caused the originally 25 m wide freshwater seepage face to decrease in width by about 5 m. The smaller seepage face reduced the area under which Fe-oxides were undergoing reductive dissolution. Consequently, the observed decrease in Fe flux is controlled by hydrology of the subterranean estuary. These results point out the need to better understand linkages between temporal variations in diagenetic reactions and changes in flow within subterranean estuaries in order to accurately constrain their contribution to oceanic fluxes of solutes from subterranean estuaries.

  10. Impacts of exotic mangrove forests and mangrove deforestation on carbon remineralization and ecosystem functioning in marine sediments

    USGS Publications Warehouse

    Sweetman, A.K.; Middelburg, J.J.; Berle, A.M.; Bernardino, A.F.; Schander, C.; Demopoulos, A.W.J.; Smith, C.R.

    2010-01-01

    To evaluate how mangrove invasion and removal can modify benthic carbon cycling processes and ecosystem functioning, we used stable-isotopically labelled algae as a deliberate tracer to quantify benthic respiration and C-flow through macrofauna and bacteria in sediments collected from (1) an invasive mangrove forest, (2) deforested mangrove sites 2 and 6 years after removal of above-sediment mangrove biomass, and (3) two mangrove-free, control sites in the Hawaiian coastal zone. Sediment oxygen consumption (SOC) rates were significantly greater in the mangrove and mangrove removal site experiments than in controls and were significantly correlated with total benthic (macrofauna and bacteria) biomass and sedimentary mangrove biomass (SMB). Bacteria dominated short-term C-processing of added microalgal-C and benthic biomass in sediments from the invasive mangrove forest habitat. In contrast, macrofauna were the most important agents in the short-term processing of microalgal-C in sediments from the mangrove removal and control sites. Mean faunal abundance and short term C-uptake rates in sediments from both removal sites were significantly higher than in control cores, which collectively suggest that community structure and short-term C-cycling dynamics in habitats where mangroves have been cleared can remain fundamentally different from un-invaded mudflat sediments for at least 6-yrs following above-sediment mangrove removal. In summary, invasion by mangroves can lead to large shifts in benthic ecosystem function, with sediment metabolism, benthic community structure and short-term C-remineralization dynamics being affected for years following invader removal. ?? 2010 Author(s).

  11. Effects of stratification, organic matter remineralization and bathymetry on summertime oxygen distribution in the Bohai Sea, China

    NASA Astrophysics Data System (ADS)

    Zhao, Hua-De; Kao, Shuh-Ji; Zhai, Wei-Dong; Zang, Kun-Peng; Zheng, Nan; Xu, Xue-Mei; Huo, Cheng; Wang, Ju-Ying

    2017-02-01

    The Bohai Sea, a semi-enclosed shallow coastal sea with increasing nutrient loads, is susceptible to seasonal oxygen deficiency in its bottom waters, similar to many other areas of the worlds' coastal oceans. We examined the dissolved oxygen (DO) distribution in the Bohai during August 2014. Two oxygen-deficient zones (DO<92 μmol O2 kg-1) with a minimum DO of 80 μmol O2 kg-1 were documented. The area and volume of bottom oxygen-deficient water were 756 km2 and 7820×106 m3, with a mean thickness of 10 m. Thus, the Bohai is second to the Changjiang estuary in its oxygen-deficient zone size among China's coastal waters. We classified three hydrographic areas that dictated the distribution of DO: 1) the shallow well-mixed zone; 2) the laterally-open stratified zone; and 3) the isolated stratified zone. Vertical mixing dominated the shallow well-mixed zone leading to homogeneous DO in the water column. The laterally-open stratified zone was influenced by high DO and low temperature inflow through the northern Bohai Strait. The isolated stratified zones, i.e., the low DO areas, were found in depressed regions. The stoichiometric relationship between DO consumption and the corresponding enrichment of dissolved inorganic carbon suggested that the aerobic respiration of organic matter contributed to the oxygen-depletion in the isolated stratified zone. Overall, the bottom DO distribution in the Bohai system was controlled largely by lateral DO exchange modified by bathymetric features, while superimposed on that was the build-up of stratification caused by summer heating and the remineralization of organics sourced from spring phytoplankton bloom.

  12. Multidecadal accumulation of anthropogenic and remineralized dissolved inorganic carbon along the Extended Ellett Line in the northeast Atlantic Ocean

    NASA Astrophysics Data System (ADS)

    Humphreys, Matthew P.; Griffiths, Alex M.; Achterberg, Eric P.; Holliday, N. Penny; Rérolle, Victoire M. C.; Menzel Barraqueta, Jan-Lukas; Couldrey, Matthew P.; Oliver, Kevin I. C.; Hartman, Susan E.; Esposito, Mario; Boyce, Adrian J.

    2016-02-01

    Marine carbonate chemistry measurements have been carried out annually since 2009 during UK research cruises along the Extended Ellett Line (EEL), a hydrographic transect in the northeast Atlantic Ocean. The EEL intersects several water masses that are key to the global thermohaline circulation, and therefore the cruises sample a region in which it is critical to monitor secular physical and biogeochemical changes. We have combined results from these EEL cruises with existing quality-controlled observational data syntheses to produce a hydrographic time series for the EEL from 1981 to 2013. This reveals multidecadal increases in dissolved inorganic carbon (DIC) throughout the water column, with a near-surface maximum rate of 1.80 ± 0.45 µmol kg-1 yr-1. Anthropogenic CO2 accumulation was assessed, using simultaneous changes in apparent oxygen utilization (AOU) and total alkalinity (TA) as proxies for the biogeochemical processes that influence DIC. The stable carbon isotope composition of DIC (δ13CDIC) was also determined and used as an independent test of our method. We calculated a volume-integrated anthropogenic CO2 accumulation rate of 2.8 ± 0.4 mg C m-3 yr-1 along the EEL, which is about double the global mean. The anthropogenic CO2 component accounts for only 31 ± 6% of the total DIC increase. The remainder is derived from increased organic matter remineralization, which we attribute to the lateral redistribution of water masses that accompanies subpolar gyre contraction. Output from a general circulation ecosystem model demonstrates that spatiotemporal heterogeneity in the observations has not significantly biased our multidecadal rate of change calculations and indicates that the EEL observations have been tracking distal changes in the surrounding North Atlantic and Nordic Seas.

  13. Are calcineurin inhibitors-free regimens ready for prime time?

    PubMed

    Vincenti, Flavio

    2012-11-01

    The goal of research in transplant therapeutics is to achieve safe and effective immunosuppression strategies that allow durable engraftment free of toxicities. The calcineurin inhibitors (CNIs) regimens, because of their inherent toxicities (including nephrotoxicity), have been unable to meet these promises. Over the past decade acute cellular rejection decreased dramatically with a concomitant robust increase in 1-year graft survival; however, long-term graft outcome showed only modest improvement. This is due in part to the toxicities of the immunosuppressive drugs. The quest for a toxicity-free-CNI-free regimen has been both intense and frustrating. A turning point in CNIs-free therapy may have occurred with the recent approval of belatacept, which represents a new paradigm in immunosuppression: biological therapy for chronic immunosuppression devoid of the usual toxicities associated with the CNIs. Belatacept, a fusion receptor protein, blocks costimulation signals necessary for the activation of T cells. Although costimulation blockade has not been shown to induce tolerance, it can provide safe and effective immunosuppression without renal or cardiovascular toxicities. The approval of belatacept in both the United States and Europe for use in renal transplantation will finally push CNI-free regimens into prime time. Novel biologics such as ASKP1240 (a human anti-CD40 monoclonal antibody) and one small molecule, tofacitinib, may advance further the use of CNI-free regimens in organ transplantation.

  14. Tuberculosis 2: exploring methods of diagnosis, treatment regimens and concordance.

    PubMed

    Jarvis, Miles

    The second in this two part unit on tuberculosis examines diagnosis and treatment options. Part I outlined background on epidemiology and control of this disease. This part draws on the guidance set out by the National Institute for Health and Clinical Excellence. Diagnostic methods are discussed and the standard treatment regimen is outlined.

  15. Heterologous Prime-Boost Immunisation Regimens Against Infectious Diseases

    DTIC Science & Technology

    2006-08-01

    Heterologous Prime-Boost Immunisation Regimens Against Infectious Diseases Susan Shahin and David Proll Human Protection and... diseases (such as malaria, tuberculosis and HIV) has been hindered by the lack of effective immunisation strategies that induce the cellular arm of...different animal and disease models. Since several intracellular pathogens are considered potential biowarfare threats, the objective of this review

  16. Roughage level and limited maximum intake regimens for feedlot steers.

    PubMed

    Bartle, S J; Preston, R L

    1992-11-01

    Hereford steers (n = 280, BW = 371 +/- 29 kg; 40 pens) were used to evaluate two alternatives to ad libitum access to feed and constant roughage levels in finishing diets. The eight treatments were as follows: two treatments in which intake was limited to a multiple of the maintenance (MM) energy requirement (2.1, 2.3, 2.5, and 2.7, [2.7MM] and 2.3, 2.5, 2.7, and 2.9 [2.9MM] times maintenance for wk 1, 2, 3, and 4 and thereafter, respectively) and six roughage regimen and grain source treatments (10% roughage equivalent [RE] fed during the mid- and late-finishing periods [10/10], respectively, 2% RE followed by 10% RE [2/10], and 10% RE followed by 2% RE [10/2] fed with steam-flaked sorghum grain [SFSG] or whole-shelled corn [WSC]). The 2.7MM treatment tended to improve ADG (6%, P = .08) and gain efficiency (4%, P = .15) relative to ad libitum access to feed. The 2.9MM treatment was intermediate. Steers fed WSC diets consumed approximately 12% more DM (9.2 vs 8.2 kg/d) and gained 4% more (1.45 vs 1.39 kg/d, P < .05) but had lower gain efficiency (7%, 159 and 170 g/kg, P < .001) than steers fed SFSG diets. For SFSG diets, the 2/10 regimen resulted in similar gains, a 3.6% decrease (P = .10) in DMI, an 8.6% improvement (P < .01) in gain efficiency, and reduced roughage use (40 kg per steer) compared with the 10/10 regimen. With WSC diets, the 2/10 regimen did not (P > .2) affect gain efficiency but did reduce roughage use (48 kg) compared with the 10/10 regimen. The 10/2 regimen did not differ (P > .2) from the 10/10 regimen. Few differences in carcass characteristics were noted among treatments. Roughage use and cost of gain can be reduced by feeding 2% roughage during the mid-finishing period followed by a return to 10% roughage.

  17. Adherence to treatment of chronic hepatitis C: from interferon containing regimens to interferon and ribavirin free regimens

    PubMed Central

    Younossi, Zobair M.; Stepanova, Maria; Henry, Linda; Nader, Fatema; Younossi, Youssef; Hunt, Sharon

    2016-01-01

    Abstract Patients’ experience during treatment may affect treatment adherence. Our aim was to assess the impact of patient-reported outcomes (PROs) on adherence to different anti-hepatitis C virus (HCV) regimens. Clinical, demographic, and PRO data (short form-36 [SF-36], chronic liver disease questionnaire-hepatitis C version [CLDQ-HCV], functional assessment of chronic illness therapy-fatigue [FACIT-F], work productivity and activity impairment: specific health problem [WPAI:SHP]) from 13 multinational clinical trials of anti-HCV treatment were available. Treatment adherence was defined as >80% of prescribed doses taken. Included were 4825 HCV patients. Regimens were grouped into: interferon- and ribavirin (RBV)-containing (±sofosbuvir [SOF]), interferon-free RBV-containing (RBV + SOF ± ledipasvir [LDV]), and interferon-free RBV-free (LDV/SOF). The adherence to these regimens were 77.6%, 84.3%, and 96.2%, respectively (P < 0.0001). Nonadherent patients were more likely to be unemployed and to have a greater PRO impairment at baseline (up to −5.3% lower PRO scores, P < 0.0001). During treatment with interferon- or RBV-based regimens, nonadherent patients experienced lower PROs and had larger decrements from their baseline PRO scores. In contrast, there were no significant declines in PRO scores (all P > 0.05) for the small number of patients who were nonadherent to LDV/SOF. In multivariate analysis, being treatment-naive, longer treatment duration, and receiving an interferon- or RBV-containing regimen were associated with a lower likelihood of adherence (all P < 0.003). Better baseline and on-treatment PRO scores were associated with a higher likelihood of adherence to interferon and RBV. The use of interferon and/or RBV, longer duration of treatment, and lower baseline and on-treatment PRO scores were linked to a decreased likelihood of being adherent to interferon + RBV-containing or interferon-free RBV-containing antiviral

  18. Optimizing anesthetic regimen for surgery in mice through minimization of hemodynamic, metabolic, and inflammatory perturbations.

    PubMed

    Zuurbier, Coert J; Koeman, Anneke; Houten, Sander M; Hollmann, Markus W; Florijn, Wouter J

    2014-06-01

    The role of anesthetics in animal research models is crucial, yet often ignored, and is almost never the primary focus of examination. Here, we investigated the impact of anesthetic regimens on different parameters of hemodynamics (blood pressure (BP) and heart rate (HR)), metabolism (glucose, insulin, and free fatty acids (FFA)), and inflammation (IL-6 and TNF-α) in two frequently used mouse strains (C57BL/6 and FVB). All animals were at a similar surgical plane of anesthesia, mechanically ventilated, and monitored for 60 min. The following anesthetic regimens were studied: (1) fentanyl-ketamine-midazolam (FKM), (2) fentanyl-midazolam-haldol (FMH), (3) pentobarbital (P), (4) fentanyl-fluanisone-midazolam (FFM), (5) fentanyl-midazolam-acepromazine (FMA), (6) ketamine-medetomidine-atropine (KMA), (7) isoflurane (ISO), and (8) propofol-fentanyl-midazolam (PFM). Metabolic and inflammatory parameters were compared with those obtained from non-anesthetized animals. Hemodynamics: BP >80 mm Hg were only obtained with KMA, whereas hypotension (BP <60 mm Hg) was observed with FKM and P. HR >500 beats/min was observed with ISO and PFM, whereas HR <400 beats/min was induced with KMA, FMH (BL/6), P (BL/6), and FKM (FVB). Metabolism: Glucose and insulin were most disturbed by KMA and ISO and mildly disturbed by FMA, whereas FFM, PFM, and P did not have any effect. FFA increased largely by FMA, with ISO and FKM having no effects. Inflammation: Cytokines were increased least with ISO/FFM/FMA, whereas FKM and KMA induced the largest increases in cytokines. When aiming at achieving surgical anesthesia without large disturbances in hemodynamic, metabolic, and inflammatory profiles, FFM, ISO, or PFM may be the most neutral anesthetic regimens in mice.

  19. Remineralizing amorphous calcium phosphate based composite resins: the influence of inert fillers on monomer conversion, polymerization shrinkage, and microhardness

    PubMed Central

    Marović, Danijela; Šariri, Kristina; Demoli, Nazif; Ristić, Mira; Hiller, Karl-Anton; Škrtić, Drago; Rosentritt, Martin; Schmalz, Gottfried; Tarle, Zrinka

    2016-01-01

    Aim To determine if the addition of inert fillers to a bioactive dental restorative composite material affects its degree of conversion (DC), polymerization shrinkage (PS), and microhardness (HV). Methods Three amorphous calcium phosphate (ACP)-based composite resins: without added fillers (0-ACP), with 10% of barium-glass fillers (Ba-ACP), and with 10% of silica fillers (Si-ACP), as well as commercial control (Ceram•X, Dentsply DeTrey) were tested in laboratory conditions. The amount of ACP (40%) and the composition of the resin mixture (based on ethoxylated bisphenol A dimethacrylate) was the same for all ACP materials. Fourier transform infrared spectroscopy was used to determine the DC (n = 40), 20 min and 72 h after polymerization. Linear PS and Vickers microhardness (n = 40) were also evaluated. The results were analyzed by paired samples t test, ANOVA, and one-way repeated measures ANOVA with Student-Newman-Keuls or Tukey’s post-hoc test (P = 0.05). Results The addition of barium fillers significantly increased the DC (20 min) (75.84 ± 0.62%) in comparison to 0-ACP (73.92 ± 3.08%), but the addition of silica fillers lowered the DC (71.00 ± 0.57%). Ceram•X had the lowest DC (54.93 ± 1.00%) and linear PS (1.01 ± 0.24%) but the highest HV (20.73 ± 2.09). PS was significantly reduced (P < 0.010) in both Ba-ACP (1.13 ± 0.25%) and Si-ACP (1.17 ± 0.19%) compared to 0-ACP (1.43 ± 0.21%). HV was significantly higher in Si-ACP (12.82 ± 1.30) than in 0-ACP (10.54 ± 0.86) and Ba-ACP (10.75 ± 0.62) (P < 0.010). Conclusion Incorporation of inert fillers to bioactive remineralizing composites enhanced their physical-mechanical performance in laboratory conditions. Both added fillers reduced the PS while maintaining high levels of the DC. Silica fillers additionally moderately improved the HV of ACP composites. PMID:27815937

  20. Box-modeling of the impacts of atmospheric nitrogen deposition and benthic remineralization on the nitrogen cycle of the eastern tropical South Pacific

    NASA Astrophysics Data System (ADS)

    Su, B.; Pahlow, M.; Oschlies, A.

    2015-09-01

    Both atmospheric deposition and benthic remineralization influence the marine nitrogen cycle, and hence ultimately also marine primary production. The biological and biogeochemical relations of the eastern tropical South Pacific (ETSP) to nitrogen deposition, benthic denitrification and phosphate regeneration are analysed in a prognostic box model of the oxygen, nitrogen and phosphorus cycles in the ETSP. In the model, atmospheric nitrogen deposition based on estimates for the years 2000-2009 is offset by half by reduced N2 fixation, with the other half transported out of the model domain. Both model- and data-based benthic denitrification are found to trigger nitrogen fixation, partly compensating for the NO3- loss. Since phosphate is the ultimate limiting nutrient in the model, enhanced sedimentary phosphate regeneration under suboxic conditions stimulates primary production and subsequent export production and NO3- loss in the oxygen minimum zone (OMZ). A sensitivity analysis of the local response to both atmospheric deposition and benthic remineralization indicates dominant stabilizing feedbacks in the ETSP, which tend to keep a balanced nitrogen inventory, i.e., nitrogen input by atmospheric deposition is counteracted by decreasing nitrogen fixation; NO3- loss via benthic denitrification is partly compensated by increased nitrogen fixation; enhanced nitrogen fixation stimulated by phosphate regeneration is partly removed by the stronger water-column denitrification. Even though the water column in our model domain acts as a NO3- source, the ETSP including benthic denitrification might become a NO3- sink.

  1. Intensified hemodialysis regimens: neglected treatment options for children and adolescents.

    PubMed

    Müller, Dominik; Zimmering, Miriam; Chan, Christopher T; McFarlane, Philip A; Pierratos, Andreas; Querfeld, Uwe

    2008-10-01

    During recent years, the importance of intensified dialysis regimens has gathered increasing interest, especially after the Hemodialysis (HEMO) Study Group reported that a higher dose of thrice-weekly hemodialysis failed to improve clinical outcomes. Long nocturnal hemodialysis (three to six times per week) or short daily hemodialysis are the currently used forms of intensified dialysis. There is substantial evidence for cardiovascular and quality-of-life improvements as well as financial benefits with intensified hemodialysis. Preliminary experience with daily hemodialysis and hemodiafiltration in children has been reported. Given the continuing shortage of donor organs for kidney transplantation, the increasing incidence of end-stage renal disease (ESRD) and recognition of the deleterious effects of long-lasting ESRD, growth retardation, and poor social rehabilitation, more intensified dialysis regimens are a much-needed therapeutical option in both adults and children.

  2. Initial dosage regimens of gentamicin in patients with burns.

    PubMed

    Zaske, D E; Chin, T; Kohls, P R; Solem, L D; Strate, R G

    1991-01-01

    For 95 patients with burns the gentamicin dosage regimen necessary to achieve optimal serum concentrations was determined. Individual elimination rates and distribution volumes for gentamicin were determined and correlated with renal function parameters and age. In patients with burns who had normal serum creatinine levels (less than 1.5 mg/dl), gentamicin clearance and thus dosage regimens can be stratified by age. Gentamicin's clearance decreased inversely with age. Initial dosage guidelines were calculated for different age groups of patients with normal levels of serum creatinine. The guidelines were developed to assist the clinician in attaining therapeutic concentrations with initial doses of gentamicin. Therapeutic serum concentrations were reached in most patients with burns dosed by these guidelines. Serum gentamicin concentrations should always be monitored during therapy, and dosages should be adjusted to ensure optimal concentrations during the course of therapy.

  3. Basis for selecting optimum antibiotic regimens for secondary peritonitis.

    PubMed

    Maseda, Emilio; Gimenez, Maria-Jose; Gilsanz, Fernando; Aguilar, Lorenzo

    2016-01-01

    Adequate management of severely ill patients with secondary peritonitis requires supportive therapy of organ dysfunction, source control of infection and antimicrobial therapy. Since secondary peritonitis is polymicrobial, appropriate empiric therapy requires combination therapy in order to achieve the needed coverage for both common and more unusual organisms. This article reviews etiological agents, resistance mechanisms and their prevalence, how and when to cover them and guidelines for treatment in the literature. Local surveillances are the basis for the selection of compounds in antibiotic regimens, which should be further adapted to the increasing number of patients with risk factors for resistance (clinical setting, comorbidities, previous antibiotic treatments, previous colonization, severity…). Inadequate antimicrobial regimens are strongly associated with unfavorable outcomes. Awareness of resistance epidemiology and of clinical consequences of inadequate therapy against resistant bacteria is crucial for clinicians treating secondary peritonitis, with delicate balance between optimization of empirical therapy (improving outcomes) and antimicrobial overuse (increasing resistance emergence).

  4. [Malaria and life at sea: prophylactic regimens on merchant ships].

    PubMed

    Michot, S

    2011-02-01

    The purpose of this article is to describe requirements for protection/treatment of malaria on merchant ships. The first part of the article reviews recent data on the incidence of malaria in seagoing personnel. The second part provides advice on mosquito-bite prevention on merchant ships. The third part presents the most important information on prophylaxis for seafarers working in malarial risk areas. Several regimens are proposed. The last part of the article discusses curative treatment for malaria on merchant ships.

  5. “Rescue” regimens after Helicobacter pylori treatment failure

    PubMed Central

    Gisbert, Javier P

    2008-01-01

    Helicobacter pylori (H pylori) infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After more than 20 years of experience in H pylori treatment, in my opinion, the ideal regimen to treat this infection is still to be found. Currently, apart from having to know first-line eradication regimens well, we must also be prepared to face treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. The choice of a “rescue” treatment depends on which treatment is used initially. If a clarithromycin-based regimen was used initially, a subsequent metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin-based combination would be a third “rescue” option. Alternatively, it has recently been suggested that levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, a quadruple regimen may be reserved as a third-line rescue option. Finally, rifabutin-based rescue therapy constitutes an encouraging empirical fourth-line strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin. Even after two consecutive failures, several studies have demonstrated that H pylori eradication can finally be achieved in almost all patients if several rescue therapies are consecutively given. Therefore, the attitude in H pylori eradication therapy failure, even after two or more unsuccessful attempts, should be to fight and not to surrender. PMID:18803350

  6. Efficacy and Safety of a Biweekly Viscosupplementation Regimen for Knee Osteoarthritis.

    PubMed

    Yiasemidou, Marina; Munir, Usama; Glassman, Daniel; Teanby, David

    2016-01-01

    Osteoarthritis is the most common form of arthritis in the Western world, causing disabling symptoms in 10% of people older than 55 years. Hyaluronic acid injections can reduce osteoarthritic pain but require three to five doses administered weekly. This preliminary study aims to assess the efficacy of a more flexible viscosupplementation regimen. Patients were given three sodium hyaluronate isotonic solution injections (Ostenil; TRB Chemedica SA, Vouvry, Switzerland), biweekly. They were then asked to record their pain before and after administration of the injections, on a visual analog score. A total of 91 knees were injected. Analysis of the data showed that the viscosupplementation injections significantly reduced the baseline pain within the first 24 to 48 hours post first injection (before injection, 68.8mm; 2 days postinjection, 48.9 mm; p < 0.001); these effects were maintained up to 6 months. No adverse effects were reported. The proposed regimen appears safe and efficient in reducing osteoarthritic pain of the knee joint. A randomized controlled study is needed to confirm these results.

  7. Drug regimens identified and optimized by output-driven platform markedly reduce tuberculosis treatment time

    PubMed Central

    Lee, Bai-Yu; Clemens, Daniel L.; Silva, Aleidy; Dillon, Barbara Jane; Masleša-Galić, Saša; Nava, Susana; Ding, Xianting; Ho, Chih-Ming; Horwitz, Marcus A.

    2017-01-01

    The current drug regimens for treating tuberculosis are lengthy and onerous, and hence complicated by poor adherence leading to drug resistance and disease relapse. Previously, using an output-driven optimization platform and an in vitro macrophage model of Mycobacterium tuberculosis infection, we identified several experimental drug regimens among billions of possible drug-dose combinations that outperform the current standard regimen. Here we use this platform to optimize the in vivo drug doses of two of these regimens in a mouse model of pulmonary tuberculosis. The experimental regimens kill M. tuberculosis much more rapidly than the standard regimen and reduce treatment time to relapse-free cure by 75%. Thus, these regimens have the potential to provide a markedly shorter course of treatment for tuberculosis in humans. As these regimens omit isoniazid, rifampicin, fluoroquinolones and injectable aminoglycosides, they would be suitable for treating many cases of multidrug and extensively drug-resistant tuberculosis. PMID:28117835

  8. Drug regimens identified and optimized by output-driven platform markedly reduce tuberculosis treatment time.

    PubMed

    Lee, Bai-Yu; Clemens, Daniel L; Silva, Aleidy; Dillon, Barbara Jane; Masleša-Galić, Saša; Nava, Susana; Ding, Xianting; Ho, Chih-Ming; Horwitz, Marcus A

    2017-01-24

    The current drug regimens for treating tuberculosis are lengthy and onerous, and hence complicated by poor adherence leading to drug resistance and disease relapse. Previously, using an output-driven optimization platform and an in vitro macrophage model of Mycobacterium tuberculosis infection, we identified several experimental drug regimens among billions of possible drug-dose combinations that outperform the current standard regimen. Here we use this platform to optimize the in vivo drug doses of two of these regimens in a mouse model of pulmonary tuberculosis. The experimental regimens kill M. tuberculosis much more rapidly than the standard regimen and reduce treatment time to relapse-free cure by 75%. Thus, these regimens have the potential to provide a markedly shorter course of treatment for tuberculosis in humans. As these regimens omit isoniazid, rifampicin, fluoroquinolones and injectable aminoglycosides, they would be suitable for treating many cases of multidrug and extensively drug-resistant tuberculosis.

  9. Toxicities of different first-line chemotherapy regimens in the treatment of advanced ovarian cancer

    PubMed Central

    Qu, Chang-Ping; Sun, Gui-Xia; Yang, Shao-Qin; Tian, Jun; Si, Jin-Ge; Wang, Yi-Feng

    2017-01-01

    Abstract Background: Ovarian cancer (OC) is the 5th leading cause of cancer-related deaths around the world, and several chemotherapy regimens have been applied in the treatment of OC. We aim to compare toxicities of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) using network meta-analysis. Methods: Literature research in Cochrane Library, PubMed, and EMBASE was performed up to November 2015. Eligible randomized controlled trials (RCTs) of different chemotherapy regimens were included. Network meta-analysis combined direct and indirect evidence to assess pooled odds ratios (ORs) and draw the surface under the cumulative ranking (SUCRA) curves. Results: Thirteen eligible RCTs were included in this network meta-analysis, including 8 chemotherapy regimens (paclitaxel + carboplatin [PC], pegylated liposomal doxorubicin [PLD] + carboplatin, carboplatin, gemcitabine + carboplatin, paclitaxel, PC + epirubicin, PC + topotecan, docetaxel + carboplatin). Gemcitabine + carboplatin regimen exerted higher incidence of anemia when compared with carboplatin and paclitaxel regimens. The incidence of febrile neutropenia of gemcitabine + carboplatin regimen was higher than that of PC, PLD + carboplatin, carboplatin, and PC + topotecan regimens. Topotecan PC + epirubicin regimen had a higher toxicity, comparing with PC, PLD + carboplatin, and PC + topotecan regimens. As for thrombocytopenia, gemcitabine + carboplatin chemotherapy regimen produced an obviously higher toxicity than PC and carboplatin. As for nausea, PLD + carboplatin chemotherapy regimen had a significantly higher toxicity than that of carboplatin chemotherapy regimen. Moreover, when compared with PC and carboplatin chemotherapy regimens, the toxicity of PC + epirubicin was greatly higher to patients with AOC. Conclusion: The nonhematologic toxicity of PLD + carboplatin regimen was higher than other regimens, which

  10. Variations in the elemental ratio of organic matter in the central Baltic Sea: Part I-Linking primary production to remineralization

    NASA Astrophysics Data System (ADS)

    Kreus, Markus; Schartau, Markus; Engel, Anja; Nausch, Monika; Voss, Maren

    2015-06-01

    For most marine ecosystems the growth of diazotrophic cyanobacteria and the associated amount of nitrogen fixation are regulated by the availability of phosphorus. The intensity of summer blooms of nitrogen (N2) fixing algae in the Baltic Sea is assumed to be determinable from a surplus of dissolved inorganic phosphorus (DIP) that remains after the spring bloom has ended. But this surplus DIP concentration is observed to continuously decrease at times when no appreciable nitrogen fixation is measured. This peculiarity is currently discussed and has afforded different model interpretations for the Baltic Sea. In our study we propose a dynamical model solution that explains these observations with variations of the elemental carbon-to-nitrogen-to-phosphorus (C:N:P) ratio during distinct periods of organic matter production and remineralization. The biogeochemical model resolves seasonal C, N and P fluxes with depth at the Baltic Sea monitoring site BY15, based on three assumptions: (1) DIP is utilized by algae though not needed for immediate growth, (2) the uptake of dissolved inorganic nitrogen (DIN) is hampered when the algae's phosphorus (P) quota is low, and (3) carbon assimilation continues at times of nutrient depletion. Model results describe observed temporal variations of DIN, DIP and chlorophyll-a concentrations along with partial pressure of carbon dioxide (pCO2). In contrast to other model studies, our solution does not require N2 fixation to occur shortly after the spring bloom to explain DIP drawdown and pCO2 levels. Model estimates of annual N2 fixation are 297 ± 24 mmol Nm-2a-1. Estimates of total production are 14200 ± 700 mmol Cm-2a-1, 1400 ± 70 mmol Nm-2a-1, and 114 ± 5 mmol Pm-2a-1 for the upper 50 m. The models C, N and P fluxes disclose preferential remineralization of P and of organic N that was introduced via N2 fixation. Our results are in support of the idea that P uptake by phytoplankton during the spring bloom contributes to the

  11. Carbon remineralization in a north Florida swamp forest: Effects of water level on the pathways and rates of soil organic matter decomposition

    NASA Astrophysics Data System (ADS)

    Happell, James D.; Chanton, Jeffrey P.

    1993-09-01

    Water level controlled gas emissions from North Florida swamp forests. Under flooded conditions, CO2 and CH4 were the principle carbon gases transported to the atmosphere by bubble ebullition and molecular diffusion. The respective emission rates were for CO2, 29.3 ± 16.4 (13% by means of ebullition, 87% by means of diffusion, error is ± 1 standard deviation throughout) and for CH4, 2.16 ± 2.24 (45% by means of ebullition, 55% by means of diffusion) mol m-2 yr-1. Methane emissions were significantly attenuated by CH4 oxidation which occurred primarily at the sediment-water interface. Forty-six ± 22 % (n=19) of the belowground CH4 diffusing to this interface was oxidized before it could escape to the atmosphere. Under dry conditions, CO2 was the principle carbon gas released and atmospheric CH4 was consumed by microbes in the soil. The respective rates were 101.2 ± 26.80 and -0.015 ± 0.005 mol mr-2 yr-1. A carbon budget for the degradation of soil organic matter was developed for a swamp forest site under flooded and dry conditions. Assuming that live root respiration accounted for 67% (value determined in a swamp forest and is at the upper range of literature values) of the total CO2 emissions (given above), we calculate that under flooded conditions carbon remineralization proceeded at a total rate of 11.9 mol C m-2 yr-1. Forty-nine percent of the remineralization was by means of nonmethanogenic processes which produce CO2; the balance was by means of methanogenic processes, which produce both CH4 and CO2. Under dry conditions, remineralization was dominated by aerobic processes at a rate of 33.7 mol C m-2 yr-1. Carbon inputs to the soil occurred by aboveground and belowground production. Aboveground litter production contributed 25.6 mol C m-2 yr-1. If belowground production contributed an equal amount, then over the course of this study organic carbon accumulated in the soils at rates of 39.3 and 17.5 mol C m-2 yr-1 under flooded and dry conditions

  12. The Washington Regimen: rehabilitation of the hand following flexor tendon injuries.

    PubMed

    Dovelle, S; Heeter, P K

    1989-12-01

    This article describes the use of the "Washington Regimen" of early controlled motion in the rehabilitation of flexor tendon injuries of the hand. This regimen is derived from a combination of Kleinert's controlled active extension with rubber-hand passive flexion, Duran's controlled passive techniques, and the modification of the Kleinert orthosis that uses a palmar pulley system. Based on results of clinical investigations, this regimen of early controlled motion appears effective in inhibiting peritendinous scarring, joint contractures, and other complications that commonly occur secondary to flexor tendon repairs. A six-week staged regimen of postoperative rehabilitation is presented. Splint design, exercise regimen, and rationale for treatment are reviewed.

  13. The influence of immunosuppressive agents on BK virus risk following kidney transplantation, and implications for choice of regimen.

    PubMed

    Suwelack, Barbara; Malyar, Viola; Koch, Martina; Sester, Martina; Sommerer, Claudia

    2012-07-01

    The increasing incidence of BK-associated nephropathy following kidney transplantation has prompted an examination of strategies for risk reduction and management through immunosuppression manipulation. Evidence from retrospective and prospective studies suggests that BK viruria and viremia, and the need for BK virus treatment, are higher with tacrolimus than cyclosporine. Combined therapy with tacrolimus and mycophenolic acid may be associated with a particularly higher risk of BK infection, but data are conflicting as to whether mycophenolic acid per se is an independent risk factor. The incidence of BK-related events may be reduced in patients receiving mTOR inhibitors (everolimus or sirolimus) with cyclosporine vs a calcineurin inhibitor with mycophenolic acid. De novo immunosuppression regimens that avoid rabbit antithymocyte globulin and tacrolimus, particularly tacrolimus with mycophenolic acid, may be advantageous, whereas low-exposure cyclosporine with an mTOR inhibitor appears a favorable option. Routine screening for BK infection during the first 2 years posttransplant is recommended to allow preemptive modification of the immunosuppressive regimen. In patients at high risk of BK virus infection, appropriate de novo immunosuppression or very early conversion to an mTOR inhibitor to facilitate reduction or discontinuation of calcineurin inhibitors or antimetabolites should be considered. Extensive further research into optimal avoidance, screening, and treatment strategies is required.

  14. Management of patients using unproven regimens for arthritis.

    PubMed

    Wolman, P G

    1987-09-01

    Such treatments as vegetarian diets, fresh or raw diets, allergy diets, no-dairy-products diets, fasting, vitamin and mineral supplementation, apple cider vinegar, and honey drinks are touted in the popular press as effective for the treatment of arthritis. In contrast to conventional therapies, the unproven treatments promise not only relief from symptoms but freedom from the disease as long as the diet regimen is followed. Several of the remedies appear to be harmless, but others are dangerous, especially if followed for prolonged periods. Nutrition professionals should be aware of the nature of these treatments and be prepared to offer sound, scientifically based but nonjudgmental care and information.

  15. Rifaximin Plus Levofloxacin-Based Rescue Regimen for the Eradication of Helicobacter pylori

    PubMed Central

    Yun, Sang-Pil; Seon, Han Gyung; Ok, Chang Soo; Yoo, Kwang Ho; Kang, Min Kyung; Kim, Won Hee; Kwon, Chang Il; Ko, Kwang Hyun; Hwang, Seong Gyu; Park, Pil Won

    2012-01-01

    Background/Aims This study assessed the efficacy of a rifaximin plus levofloxacin-based rescue regimen in patients that had failed both triple and quadruple standard regimens for the eradication of Helicobacter pylori. Methods We treated patients for H. pylori between August 2009 and April 2011. The triple regimen consisted of combined treatment with amoxicillin, clarithromycin, and pantoprazole for 1 week. For failed cases, a quadruple regimen of tetracycline, metronidazole, bismuth dicitrate, and lansoprazole for 1 week was administered. The rescue regimen for persistently refractory cases was rifaximin 200 mg t.i.d., levofloxacin 500 mg q.d., and lansoprazole 15 mg b.i.d. for 1 week. Results In total, 482 patients were enrolled in this study. The eradication rates associated with the first and second regimens were 58% and 60%, respectively. Forty-seven out of 58 patients who failed with the second-line regimen received rifaximin plus levofloxacin-based third-line therapy. The eradication rate for the third regimen was 65%. The cumulative eradication rates were 58%, 85%, and 96% for each regimen, respectively. Conclusions A rifaximin plus levofloxacin-based regimen could be an alternative rescue therapy in patients with resistance to both triple and quadruple regimens for the eradication of H. pylori. PMID:23170149

  16. Suction clearance and 2% topical miconazole versus the same combination with acidic drops in the treatment of otomycosis.

    PubMed

    Kiakojuri, Kayvan; Roushan, Mohammad Reza Hasanjani; Sepidgar, Seyed Ali Asghar

    2007-07-01

    From April 2003 to September 2004, 59 ears from 55 patients received suction clearance and topical miconazole 2% (regimen 1) and in September 2004 to December 2005, 64 ears from 58 patients received the same combinations plus acidic drops [acetic acid 3% (v/ v) in 97% ethanol]. The mean age of patients treated with regimen 1 was 35.76+/-16 years and in regimen 2 was 37.98+/-15 years. Aspergilus sp and Candida sp were seen in 35 (59.3%) and 24 (40.7%) cases treated with regimen 1 and in 43 (67.2%) and 21 (32.8%) cases treated in regimen 2, respectively. Relapse occurred in 2 (3.4%) ears treated with regimen 1, but none in cases treated with regimen 2 (p=0.228). The findings reveal that there were no statistically significant differences between the two regimens and both may be used for the treatment of otomycosis.

  17. In vitro evaluation of different remineralization periods in improving the resistance of previously eroded bovine dentine against tooth-brushing abrasion.

    PubMed

    Attin, T; Buchalla, W; Putz, B

    2001-09-01

    One dentine specimen was prepared from each of 90 bovine incisors. The samples were then evenly distributed among nine groups (A-I) and submitted to 10 alternating de- and re-mineralization cycles, including abrasion by tooth brushing. Each cycle started with a demineralization using the erosive soft drink Sprite Light for 1 min, followed by storing the samples in pooled human saliva for a total of 240 min. The specimens were removed from the saliva at different intervals (group A, 0 min; B, 15 min; C, 30 min; D, 45 min; E, 60 min; F, 90 min; G, 120 min) and brushed in an automatic brushing machine. Groups H (erosion, but no brushing) and I (no erosion, but brushing), which were also stored in saliva for 240 min, served as controls. After these cycles, loss of dentine was determined by profilometry, producing the following values (mean+/-S.D.), which were analysed statistically (P< or = 0.05): group A (5.03+/-1.49 microm), B (4.44+/-1.09 microm), C (4.91+/-0.95 microm), D (5.47+/-1.52 microm), E (5.29+/-1.45 microm), F (4.76+/-0.74 microm), G (5.16+/-0.71 microm), H (2.61+/-1.31), I (1.11+/-0.39). Groups A-G had no significant differences, but they showed a significantly greater loss of dentine than groups H and I. It is concluded that the abrasion resistance of eroded bovine dentine is still decreased after a remineralization period of 120 min.

  18. A New Weak Chelator in Endodontics: Effects of Different Irrigation Regimens with Etidronate on Root Dentin Microhardness

    PubMed Central

    Tartari, Talita; de Almeida Rodrigues Silva e Souza, Patrícia; Vila Nova de Almeida, Bruno; Carrera Silva Júnior, José Otávio; Facíola Pessoa, Oscar; Silva e Souza Junior, Mario Honorato

    2013-01-01

    This study investigated the effect of sodium hypochlorite (NaOCl), ethylenediaminetetraacetic (EDTA), etidronic (HEBP), and citric acid (CA) associated in different irrigation regimens on root dentin microhardness. Forty-five root halves of single-rooted teeth were sectioned into thirds that were embedded in acrylic resin, polished, randomly assigned into 3 groups, and treated as follows: G1: saline solution; G2: 5% NaOCl + 18% HEBP, mixed in equal parts; and G3: 2.5% NaOCl. After measurements, the G3 samples were distributed into subgroups G4, G5, and G6, which were submitted to 17% EDTA, 10% CA and 9% HEBP, respectively. Following the new measurements, these groups received a final flush with 2.5% NaOCl, producing G7, G8, and G9. Microhardness was measured with Knoop indenter under a 25 g load for 15 seconds, before and after treatments. The data were statistically analyzed using paired Student's t-test (α<0.05) to compare values before and after treatments and analysis of variance (ANOVA) (α<0.05) to detect any differences among thirds. Except G1, all tested irrigation regimens significantly decreased the microhardness. There were no differences between root thirds before treatments, and all root thirds exhibited equal responses to same treatment. Except saline, all tested irrigation regimens reduced the root dentin microhardness. PMID:23983692

  19. Logistics of therapy with the ibritumomab tiuxetan regimen

    SciTech Connect

    Meredith, Ruby F. . E-mail: rmeredith@uabmc.edu

    2006-10-01

    Radioimmunotherapy is an important new modality for treating patients with B-cell non-Hodgkin's lymphoma (NHL). Clinical trials have shown the safety and efficacy of agents that deliver radiation directly to malignant cells by attaching the {sup 131}I or {sup 9}Y radionuclide to monoclonal antibodies against CD20. In clinical trials, {sup 9}Y ibritumomab tiuxetan has produced rates of response as high as 83% in patients with relapsed or refractory CD20+ NHL. The ibritumomab tiuxetan regimen is conveniently given in an outpatient setting over the course of 7-9 days. This article describes the logistics for initiating treatment, coordinating a multidisciplinary team, identifying eligible patients, and delivering the imaging and therapeutic doses of ibritumomab tiuxetan. The standard radiation safety procedures to protect family members and healthcare professionals involved in the care of patients treated with {sup 9}Y ibritumomab tiuxetan are also reviewed. Treatment with the ibritumomab tiuxetan regimen involves only standard precautions needed to minimize radiation exposure to other persons.

  20. Remission-Induction Regimens in Acute Nonlymphocytic Leukemia

    PubMed Central

    Brennan, Donald C.; Lewis, Jerry P.

    1980-01-01

    A sequential study was carried out involving 40 adults with acute nonlymphocytic leukemia (ANLL). The first 20 patients were treated with cytarabine (Ara-C) and 6-thioguanine (6-TG), the second 20 with a regimen that added a three-day course of daunomycin (DNM) to the Ara-C and 6-TG therapy. With both groups well matched for age, patients in the DNM-treated group had a higher complete remission (CR) rate but failed to survive longer than those in the Ara-C and 6-TG treatment group. In a comprehensive literature review of various treatments for adult ANLL, a higher CR rate but not significantly better survival for patients initially treated with DNM-combined regimens was found. Our analysis of cases and literature review suggest that while DNM is a very active drug, its use in the initial treatment of adult ANLL has not produced a significant improvement in overall survival or in survival of those brought into complete remission. PMID:7347042

  1. New anti-tuberculosis drugs and regimens: 2015 update

    PubMed Central

    D'Ambrosio, Lia; Centis, Rosella; Sotgiu, Giovanni; Pontali, Emanuele; Spanevello, Antonio; Migliori, Giovanni Battista

    2015-01-01

    Over 480 000 cases of multidrug-resistant (MDR) tuberculosis (TB) occur every year globally, 9% of them being affected by extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. The treatment of MDR/XDR-TB is unfortunately long, toxic and expensive, and the success rate largely unsatisfactory (<20% among cases with resistance patterns beyond XDR). The aim of this review is to summarise the available evidence-based updated international recommendations to manage MDR/XDR-TB, and to update the reader on the role of newly developed drugs (delamanid, bedaquiline and pretomanid) as well as repurposed drugs (linezolid and meropenem clavulanate, among others) used to treat these conditions within new regimens. A nonsystematic review based on historical trials results as well as on recent literature and World Health Organization (WHO) guidelines has been performed, with special focus on the approach to managing MDR/XDR-TB. The new, innovative global public health interventions, recently approved by WHO and known as the “End TB Strategy”, support the vision of a TB-free world with zero death, disease and suffering due to TB. Adequate, universally accessed treatment is a pre-requisite to reach TB elimination. New shorter, cheap, safe and effective anti-TB regimens are necessary to boost TB elimination. PMID:27730131

  2. The comparison between two irrigation regimens on the dentine wettability for an epoxy resin based sealer by measuring its contact angle formed to the irrigated dentine

    PubMed Central

    Mohan, Rayapudi Phani; Pai, Annappa Raghavendra Vivekananda

    2015-01-01

    Aim: The aim was to assess the influence of two irrigation regimens having ethylenediaminetetraacetic acid (EDTA) and ethylenediaminetetraacetic acid with cetrimide (EDTAC) as final irrigants, respectively, on the dentine wettability for AH Plus sealer by comparing its contact angle formed to the irrigated dentine. Materials and Methods: Study samples were divided into two groups (n = 10). The groups were irrigated with 3% sodium hypochlorite (NaOCl) solution followed by either 17% EDTA or 17% EDTAC solution. AH Plus was mixed, and controlled volume droplet (0.1 mL) of the sealer was placed on the dried samples. The contact angle was measured using a Dynamic Contact Angle Analyzer and results were analyzed using SPSS 21.0 and 2 sample t-test. Results: There was a significant difference in the contact angle of AH Plus formed to the dentine irrigated with the above two regimens. AH Plus showed significantly lower contact angle with the regimen having EDTAC as a final irrigant than the one with EDTA (P < 0.05). Conclusion: An irrigation regimen consisting of NaOCl with either EDTA or EDTAC solution as a final irrigant influences the dentine wettability and contact angle of a sealer. EDTAC as a final irrigant facilitates better dentin wettability than EDTA for AH Plus to promote its better flow and adhesion. PMID:26180409

  3. Gefitinib, Fluorouracil, Oxaliplatin, and Leucovorin (IFOX) Regimen for Colorectal Cancer

    PubMed Central

    Chen, Alicia S.; Solimando, Dominic A.; Waddell, J. Aubrey

    2013-01-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. PMID:24474830

  4. Comparison of different regimens for surgical hand preparation.

    PubMed

    Larson, E L; Aiello, A E; Heilman, J M; Lyle, C T; Cronquist, A; Stahl, J B; Della-Latta, P

    2001-02-01

    Twenty surgical staff members participated in a clinical trial to compare the microbiology and skin condition of hands when using a traditional surgical scrub (TSS) with a detergent-based antiseptic containing 4% chlorhexidine gluconate (CHG) and a short application without scrub of a waterless hand preparation (HP) containing 61% ethyl alcohol, 1% CHG, and emollients. The HP was associated with less skin damage (P = .002) and lower microbial counts postscrub at days five (P = .002) and 19 (P = .02). The HP protocol had shorter contact time (HP mean [M] = 80.7 seconds; TSS M = 144.9 seconds; P < .0001), and more subjects preferred the HP regimen (P = .001). The HP performed better than the TSS, was less costly, and should be evaluated in larger trials and considered for widespread implementation.

  5. Levothyroxine Treatment in Pregnancy: Indications, Efficacy, and Therapeutic Regimen

    PubMed Central

    Klubo-Gwiezdzinska, Joanna; Burman, Kenneth D.; Van Nostrand, Douglas; Wartofsky, Leonard

    2011-01-01

    The prevalence of overt and subclinical hypothyroidism during pregnancy is estimated to be 0.3–0.5% and 2–3%, respectively. Thyroid autoantibodies are found in 5–18% of women in the childbearing age. The aim of this review is to underscore the clinical significance of these findings on the health of both the mother and her offspring. Methods of evaluation of thyroid function tests (TFTs) during pregnancy are described as are the threshold values for the diagnosis of overt and subclinical hypothyroidism or hypothyroxinemia. Anticipated differences in TFTs in iodine-sufficient and iodine-deficient areas are discussed and data are provided on potential complications of hypothyroidism/hypothyroxinemia and autoimmune thyroid disease during pregnancy and adverse effects for the offspring. The beneficial effects of levothyroxine therapy on pregnancy outcomes and offspring development are discussed with a proposed treatment regimen and follow up strategy. PMID:21876837

  6. Current regimens and novel agents for mantle cell lymphoma.

    PubMed

    Chen, Yiming; Wang, Michael; Romaguera, Jorge

    2014-10-01

    Mantle cell lymphoma is a heterogeneous subtype of non-Hodgkin lymphoma. Conventional treatment with immunochemotherapy followed by autologous stem cell transplantation or intensive immunochemotherapy alone has improved outcomes, but the disease remains incurable. Recent advances in basic and translational research have significantly enhanced our understanding of disease pathogenesis and have sparked the development of novel therapies. Novel agents include the proteasome inhibitor bortezomib, the immunomodulatory agent lenalidomide, the phosphatidylinositol-4,5-bisphosphate 3-kinase pathway inhibitor idelalisib and the Bruton tyrosine kinase inhibitor ibrutinib. Preliminary results from clinical trials, especially from studies of ibrutinib, have proven these agents to be effective. In ongoing studies, these agents are being integrated into conventional immunochemotherapy regimens to hopefully improve patient outcomes.

  7. Regimen selection in the OPTIONS trial of HIV salvage therapy: drug resistance, prior therapy, and race–ethnicity determine the degree of regimen complexity

    PubMed Central

    Tashima, Karen T.; Mollan, Katie R.; Na, Lumine; Gandhi, Rajesh T.; Klingman, Karin L.; Fichtenbaum, Carl J.; Andrade, Adriana; Johnson, Victoria A.; Eron, Joseph J.; Smeaton, Laura; Haubrich, Richard H.

    2015-01-01

    Background Regimen selection for highly treatment-experienced patients is complicated. Methods Using a web-based utility, study team members reviewed antiretroviral (ARV) history and resistance data and recommended individual ARV regimens and nucleoside reverse transcriptase inhibitor (NRTI) options for treatment-experienced participants consisting of 3–4 of the following agents: raltegravir (RAL), darunavir (DRV)/ritonavir, tipranavir (TPV)/ritonavir, etravirine (ETR), maraviroc (MVC), and enfuvirtide (ENF). We evaluated team recommendations and site selection of regimen and NRTIs. Associations between baseline factors and the selection of a complex regimen (defined as including four ARV agents or ENF) were explored with logistic regression. Results A total of 413 participants entered the study. Participants initiated the first or second recommended regimen 86% of the time and 21% of participants started a complex regimen. In a multivariable model, ARV resistance to NRTI (odds ratio [OR]=2.2), non-nucleoside reverse transcriptase inhibitor (NNRTI, OR=6.2) or boosted protease inhibitor (PI, OR=6.6), prior use of integrase strand transfer inhibitor (INSTI, OR=25), and race–ethnicity (all P≤0.01) were associated with selection of a complex regimen. Black non-Hispanic (OR=0.5) and Hispanic participants from the continental US (OR=0.2) were less likely to start a complex regimen, compared to white non-Hispanics. Conclusions In this multi-center trial, we developed a web-based utility that facilitated treatment recommendations for highly treatment-experienced patients. Drug resistance, prior INSTI use, and race–ethnicity were key factors in decisions to select a more complex regimen. PMID:26212575

  8. Dilemma of first line regimens in metastatic pancreatic adenocarcinoma

    PubMed Central

    Ghosn, Marwan; Ibrahim, Tony; Assi, Tarek; El Rassy, Elie; Kourie, Hampig Raphael; Kattan, Joseph

    2016-01-01

    Pancreatic cancer is one of the deadliest cancers, ranking fourth among cancer-related deaths. Despite all the major molecular advances and treatment breakthroughs, mainly targeted therapies, the cornerstone treatment of metastatic pancreatic cancer (mPC) remains cytotoxic chemotherapy. In 2016, more than 40 years after the introduction of gemcitabine in the management of mPC, the best choice for first-line treatment has not yet been fully elucidated. Two main strategies have been adopted to enhance treatment efficacy. The first strategy is based on combining non-cross resistant drugs, while the second option includes the development of newer generations of chemotherapy. More recently, two new regimens, FOLFIRINOX and gemcitabine/nab-paclitaxel (GNP), have both been shown to improve overall survival in comparison with gemcitabine alone, at the cost of increased toxicity. Therefore, the best choice for first line therapy is a matter of debate. For some authors, FOLFIRINOX should be the first choice in patients with an Eastern Cooperative Oncology Group score (0-1) given its lower hazard ratio. However, others do not share this opinion. In this paper, we review the main comparison points between FOLFIRINOX and GNP. We analyze the two pivotal trials to determine the similarities and differences in study design. In addition, we compare the toxicity profile of the two regimens as well as the impact on quality of life. Finally, we present studies revealing real life experiences and review the advantages and disadvantages of possible second-line therapies including their cost effectiveness. PMID:28028360

  9. Superiority of Interferon-Free Regimens for Chronic Hepatitis C

    PubMed Central

    Younossi, Zobair M.; Stepanova, Maria; Esteban, Rafael; Jacobson, Ira; Zeuzem, Stefan; Sulkowski, Mark; Henry, Linda; Nader, Fatema; Cable, Rebecca; Afendy, Mariam; Hunt, Sharon

    2017-01-01

    Abstract Patient-reported outcomes (PROs) such as quality of life and work productivity are important for measuring patient's experience. We assessed PROs during and after treatment of hepatitis C virus (HCV) patients. Data were obtained from a phase 3 open label study of sofosbuvir and ribavirin (SOF + RBV) with and without interferon (IFN). Patients completed 4 PRO assessment instruments (SF-36, Functional Assessment of Chronic Illness Therapy—Fatigue, Chronic Liver Disease Questionnaire— HCV, Work Productivity and Activity—Specific Health Problem) before, during, and after treatment. A total of 533 patients with chronic HCV were enrolled; 28.9% treatment-naïve, 23.1% cirrhotic, 219 received IFN + SOF + RBV and 314 received IFN-free SOF + RBV. At baseline, there were no differences in PROs between the IFN-free and IFN-containing treatment arms (all P > 0.05). During treatment, patients receiving IFN + SOF + RBV had a substantial impairment in their PROs (up to −24.4% by treatment week 12, up to −8.3% at week 4 post-treatment). The PRO decrements seen in the SOF + RBV arm were smaller in magnitude (up to −7.1% by treatment week 12), and all returned to baseline or improved by post-treatment week 4. By 12 weeks after treatment cessation, patients who achieved sustained viral response-12 showed some improvement of PRO scores regardless of the regimen (up to +7.1%, P < 0.0001) or previous treatment experience. In multivariate analysis, the use of IFN was independently associated with lower PROs. IFN-based regimens have a profoundly negative impact to PROs. By contrast, the impact of RBV on these PROs is relatively modest. Achieving HCV cure is associated with improvement of most of the PRO scores. PMID:28207507

  10. A study of parenteral iron regimens in hemodialysis patients.

    PubMed

    Besarab, A; Kaiser, J W; Frinak, S

    1999-07-01

    The administration of parenteral iron dextran to hemodialysis patients is typically intermittent. We sought to determine the most appropriate intervals for sampling iron parameters during intermittent need-based and continuous maintenance regimens and to quantify differences in efficacy between such regimens during long-term therapy. After a single course of 10 consecutive 100-mg iron doses administered to 14 patients on 16 occasions, transferrin saturation (TSAT) and ferritin were unreliable indices of iron status for the next 2 and 6 weeks, respectively. TSAT and ferritin levels at 1 week were virtually identical to those at 2 weeks after the administration of a single 50-mg or 100-mg iron dextran dose to 16 other patients. Twelve patients on maintenance iron therapy (25 to 100 mg/wk; TSAT, 30% to 50%) had a statistically significant decrease in the amount of recombinant human erythropoietin (rHuEPO) needed to maintain hemoglobin (Hb) levels between 10 and 11 g/dL compared with 12 patients receiving intermittent need-based dosing, an effect that persisted from week 16 to week 72 of the study. Maintenance iron was feasible even in a third group of eight patients targeted to sustain an Hb level of 14 g/dL. In both iron maintenance groups, iron indices could be measured at weekly intervals, and ferritin levels did not progressively increase over time. Continuous maintenance iron dextran used to maintain TSATs of 30% to 50% significantly reduced rHuEPO requirements and resulted in no adverse side effects in chronic hemodialysis patients. After weekly maintenance 25- to 100-mg iron dextran doses, iron indices can be measured after 1 week; a delay of 2 weeks is not necessary.

  11. Extended regimen combined oral contraception: A review of evolving concepts and acceptance by women and clinicians

    PubMed Central

    Nappi, Rossella E.; Kaunitz, Andrew M.; Bitzer, Johannes

    2016-01-01

    ABSTRACT Objectives: The clinical utility of extended regimen combined oral contraceptives (COCs) is increasingly being recognised. Our objective was to understand the attitudes of women and clinicians about the use of these regimens. We present the rationale for extended regimen COCs from a historical perspective, and trace their evolution and growing popularity in light of their clinical benefits. We conclude by offering potential strategies for counselling women about extended regimen COC options. Methods: We conducted a MEDLINE search to identify and summarise studies of extended regimen COCs, focusing on attitudes of women and clinicians regarding efficacy, safety/tolerability and fewer scheduled bleeding episodes and other potential benefits. Results: The body of contemporary literature on extended regimen COCs suggests that their contraceptive efficacy is comparable to that of conventional 28-day (i.e., 21/7) regimens. For women seeking contraception that allows infrequent scheduled bleeding episodes, particularly those who suffer from hormone withdrawal symptoms and cyclical symptoms (e.g., headache, mood changes, dysmenorrhoea, heavy menstrual bleeding), extended regimen COCs are an effective and safe option. Although satisfaction with extended regimen COCs in clinical trials is high, misperceptions about continuous hormone use may still limit the widespread acceptance of this approach. Conclusions: Despite the widespread acceptance among clinicians of extended regimen COCs as an effective and safe contraceptive option, these regimens are underused, likely due to a lack of awareness about their availability and utility among women. Improved patient education and counselling regarding the safety and benefits of extended regimen COCs may help women make more informed contraceptive choices. PMID:26572318

  12. Treatment regimens and health care utilization in children with persistent asthma symptoms.

    PubMed

    Yoos, H Lorrie; Kitzman, Harriet; Halterman, Jill S; Henderson, Charles; Sidora-Arcoleo, Kimberly; McMullen, Ann

    2006-01-01

    This study evaluated the anti-inflammatory medication regimens in children with persistent asthma, determined their health care utilization patterns, and evaluated factors associated with failure to seek and/or receive appropriate treatment. Parents of 68% of children who qualified for anti-inflammatory medications by National Asthma Education and Prevention Program (NAEPP) guidelines reported their use. However, only 14% received an optimal regimen (mild intermittent symptoms), while 55% were still symptomatic despite reported medications (suboptimal regimen). Nearly half of symptomatic children did not have a health care visit; of those who did, 61% had no corrective action documented. Factors contributing to variations in regimen and utilization are discussed.

  13. New drugs and regimens for treatment of TB

    PubMed Central

    Leibert, Eric; Rom, William N

    2013-01-01

    Tools for effective TB control have been available for years. Case finding, active medications, case management and directly observed therapy are the foundations for the management of TB. The current TB epidemic, centered in resource-limited settings is fueled by the HIV-1 epidemic. Lack of ability to diagnose and treat drug-resistant TB has led to development of more extensive patterns of resistance. Among the currently available drugs, there is reason to hope that rifamycins paired with fluoroquinolones will lead to shorter treatment regimens for drug-susceptible TB. As the result of novel public-private collaborations and investments of resources, new drugs are being developed. These include TMC207, already shown to have activity early in the treatment of multidrug-resistant TB and others that are likely to be active against persistor organisms, and have the prospect to dramatically shorten treatment courses for active and latent TB. Given that these drugs have novel mechanisms of action, combinations have the prospect to be highly active even against multidrug-resistant organisms. PMID:20586565

  14. Optimization of anti-infective dosing regimens during online haemodiafiltration

    PubMed Central

    Zandvliet, Anthe S.; Touw, Daniel J.; Penne, Erik L.

    2017-01-01

    Abstract Online haemodiafiltration (HDF) is increasingly used in clinical practice as a routine intermittent dialysis modality. It is well known that renal impairment and renal replacement therapy can substantially affect the pharmacokinetic behaviour of several drugs. However, surprisingly few data are available on the need for specific dose adjustments during HDF. Due to convection, drug clearance may be increased during HDF as compared with standard haemodialysis. This may be of particular interest in patients undergoing anti-infective therapy, since under-dosing may compromise patient outcomes and promote the emergence of bacterial resistance. Drug clearance during HDF is determined by (i) dialysis characteristics, (ii) drug characteristics and (iii) patient characteristics. In this review, we will discuss these different determinants of drug clearance during HDF and advise on how to adjust the dose of antibacterial, antimycotic and antiviral agents in patients undergoing HDF. In addition, the possible added value of therapeutic drug monitoring is discussed. The review provides guidance for optimization of anti-infective dosing regimens in HDF patients.

  15. Pharmacoeconomic consequences of variable patient compliance with prescribed drug regimens.

    PubMed

    Urquhart, J

    1999-03-01

    Variable compliance with prescribed drug regimens is a leading source of variability in drug response. Specifics differ by drug and disease. The role of variable compliance was clearly defined in 2 trials of lipid-lowering agents, cholestyramine and gemfibrozil, in which exceptionally careful measurements of compliance were made, which has not been done in later trials. Economic consequences of variable compliance are estimated by converting dose-dependent changes in absolute risk of incident coronary disease into the unicohort format, which designates how many patients must be treated to prevent, in a given time, a defined 'coronary event'. Two strong influences on the costs of treatment are: (i) the shape of the relation between drug intake and risk reduction; and (ii) the strength of the linkage between intake and prescription refills. The intake-effect relation for cholestyramine is linear, making compliance-neutral the cost to prevent 1 coronary event, provided that refills match intake. If refills exceed intake, treatment costs rise. The intake-effect relation for gemfibrozil is more typically nonlinear, so poorer compliers purchase and take the drug in amounts that have little benefit, increasing the cost to prevent 1 coronary event. If refills run at a higher rate than intake, costs increase still further. A key question for future study is: do policies that encourage timely refills increase compliance enough to offset their potential to waste money in the purchasing of an untaken drug?

  16. Individualizing amikacin regimens: accurate method to achieve therapeutic concentrations.

    PubMed

    Zaske, D E; Cipolle, R J; Rotschafer, J C; Kohls, P R; Strate, R G

    1991-11-01

    Amikacin's pharmacokinetics and dosage requirements were studied in 98 patients receiving treatment for gram-negative infections. A wide interpatient variation in the kinetic parameters of the drug occurred in all patients and in patients who had normal serum creatinine levels or normal creatinine clearance. The half-life ranged from 0.7 to 14.4 h in 74 patients who had normal serum creatinine levels and from 0.7 to 7.2 h in 37 patients who had normal creatinine clearance. The necessary daily dose to obtain therapeutic serum concentrations ranged from 1.25 to 57 mg/kg in patients with normal serum creatinine levels and from 10 to 57 mg/kg in patients with normal creatinine clearance. In four patients (4%), a significant change in baseline serum creatinine level (greater than 0.5 mg/dl) occurred during or after treatment, which may have been amikacin-associated toxicity. Overt ototoxicity occurred in one patient. The method of individualizing dosage regimens provided a clinically useful means of rapidly attaining therapeutic peak and trough serum concentrations.

  17. Oxygen regimen in the human peripheral tissue during space flights

    NASA Astrophysics Data System (ADS)

    Haase, H.; Kovalenko, E. A.; Vacek, A.; Bobrovnickij, M. P.; Jarsumbeck, B.; Semencov, V. N.; Sarol, Z.; Hideg, J.; Zlatarev, K.

    A survey of the results of the experiment "Oxygen," carried out within the scope of the INTERKOSMOS program in members of the permanent crews and of international visiting expeditions to the Soviet orbital station Salyut-6, is given. During the 7-day space flights of the international visiting expeditions a significant decrease in pO 2 ic by 3.28 kPa was observed. Local oxygen utilization reduced significantly by 0.44 kPa. During hyperventilation testing after return to earth a statistically significant decrease in the peak value by 1.39 kPa was noted. In the long-term crews of the orbital station Salyut-6 the highest decrease in pO 2 ic of 3.8 kPa and the absolutely lowest value of 3.4 ± 0.5 kPa during space flight were observed. The decrease in local oxygen utilization during the flight of 0.8 kPa/min was greater than that of the visiting crews. The results indicate the importance of investigating the dynamics of the oxygen regimen for medical control of the crew members both during the space flight and during the readaptation phase after return to earth.

  18. Comparison of Non-myeloablative Conditioning Regimens for Lymphoproliferative Disorders

    PubMed Central

    Hong, Sanghee; Le-Rademacher, Jennifer; Artz, Andrew; McCarthy, Philip L.; Logan, Brent R.; Pasquini, Marcelo C.

    2014-01-01

    Hematopoietic cell transplantation (HCT) with non-myeloablative conditioning (NMA) for lymphoproliferative diseases (LD) includes fludarabine with and without low-dose total body irradiation (TBI). Transplant outcomes were compared among patients ≥40 years with LD who received a HCT with TBI (N=382) and no-TBI (N=515) NMA from 2001 to 2011. The groups were comparable except for donor, graft, prophylaxis for graft-versus-host disease (GVHD), disease status and year of HCT. Cumulative incidences of grades II–IV GVHD at 100 days, were 29% and 20% (p=0.001), and chronic GVHD at 1 year were 54% and 44% (p=0.004) for TBI and no-TBI, respectively. Multivariate analysis of progression/relapse, treatment failure and mortality showed no outcome differences by conditioning. Full donor chimerism at day 100 was observed in 82% vs. 64% in the TBI and no-TBI groups, respectively (p=0.006). Subset of four most common conditioning/ GVHD prophylaxis combinations demonstrated higher rates of grades II–IV acute (p<0.001) and chronic GVHD (p<0.001) among recipients of TBI-mycophenolate mofetil (MMF) compared to other combinations. TBI-based NMA conditioning induces faster full donor chimerism but overall survival outcomes are comparable to no-TBI regimens. Combination of TBI and MMF are associated with higher rates of GVHD without impact on survival outcomes in patients with LD. PMID:25437248

  19. Analytical verification of waterborne chemical treatment regimens in hatchery raceways

    USGS Publications Warehouse

    Rach, J.J.; Ramsay, R.T.

    2000-01-01

    Chemical therapy for control and prevention of fish diseases is a necessary and common practice in aquaculture. Many factors affect the accuracy of a chemical treatment application, such as the functioning of the chemical delivery system, calculation of chemical quantities to be delivered, water temperature, geometry of the culture unit, inlet-outlet structure, the influence of aerators, wind movement, and measurement of water volumes and flow rates. Three separate trials were conducted at the Osceola Fish Hatchery, a facility of the Wisconsin Department of Natural Resources, evaluating the accuracy of flow-through hydrogen peroxide treatments applied to 1, 3, or 9 raceways that were connected in series. Raceways were treated with 50 or 75 ??L/L of hydrogen peroxide for 30 min. Chemical concentrations were determined titrimetrically. The target treatment regimen was not realized in any of the applications. Chemical concentrations dropped and exposure times increased with each additional raceway treated in series. Single introduction of a therapeutant to more than three raceways in series is not recommended. Factors that interfered with the accuracy of the treatments were culture unit configuration, aeration, and flow rates. Several treatment modifications were identified that would result in more accurate chemical treatments.

  20. Polypathology, polypharmacy, medication regimen complexity and drug therapy appropriateness.

    PubMed

    Gómez Aguirre, N; Caudevilla Martínez, A; Bellostas Muñoz, L; Crespo Avellana, M; Velilla Marco, J; Díez-Manglano, J

    2017-02-16

    Polypathological patients are usually elderly and take numerous drugs. Polypharmacy affects 85% of these individuals and is not associated with greater survival. On the contrary, polypharmacy exposes these individuals to more adverse effects, such as weight loss, falls, functional and cognitive impairment and hospitalisations. The complexity of a drug regimen covers more aspects than the simple number of drugs consumed. The galenic form, the dosage and the method for preparing the drug can impede the understanding of and compliance with prescriptions. Both polypharmacy and therapeutic complexity are associated with poorer adherence by patients. To prevent polypharmacy, reduce complexity and improve adherence, the appropriate use of drugs is needed. Proper prescribing consists of selecting drugs that have clear evidence for their use in the indication, which are appropriate for the patient's circumstances, are well tolerated and cost-effective and whose benefits outweigh the risks. To improve the drug prescription, periodic reviews of the drugs need to be conducted, especially when the patient changes doctor and during healthcare transitions. The Beers and STOPP/START (Screening Tool of Older Person's potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment) criteria are effective tools for this improvement. Deprescription for polymedicated polypathological patients that considers their clinical circumstances, prognosis and preferences can contribute to a more appropriate use of drugs.

  1. Possibilities and potential roles of the functional peptides based on enamel matrix proteins in promoting the remineralization of initial enamel caries.

    PubMed

    Ieong, Cheng Cheng; Zhou, Xue Dong; Li, Ji Yao; Li, Wei; Zhang, Ling Lin

    2011-03-01

    Dental caries is the most common oral diseases, and it gives a serious threat to oral and general health. Fluoride, a classic anti-caries agent, has a profound effect on caries prevention and treatment. However, fluorosis and fluoride-resistant strains limit the further application of fluoride treatment. Therefore, it is still of significant benefit to seek alternatives, bringing more effective anti-caries agents. The potential role of enamel matrix proteins(EMPs) in promoting the regeneration of periodontal tissue and inducing bone have been proved. EMPs have been successfully applied in the field of periodontal disease and dental implants in recent years. Previous researches revealed that enamel matrix proteins had an important role in the synthesis of hydroxyapatite in vitro. Some experiments about the degeneration or removal of EMP suggest that enamel matrix proteins are related to the occurrence and development of caries. Based on evidences illustrated by these experiments, this paper hypothesizes that functional peptides based on the function and structure of EMPs could promote remineralization of enamel caries, which could perform as a suitable treatment to enamel caries. The hypothesis may lead a new direction in the study on the prevention and treatment of enamel caries, and further study of the anti-caries mechanisms of EMP will enable researchers to find out the most effective anti-caries peptides, which could be developed into a bionics anti-cariogenic agent.

  2. Assessing the sensitivity of modeled air-sea CO2 exchange to the remineralization depth of particulate organic and inorganic carbon

    NASA Astrophysics Data System (ADS)

    Schneider, Birgit; Bopp, Laurent; Gehlen, Marion

    2008-09-01

    To assess the sensitivity of surface ocean pCO2 and air-sea CO2 fluxes to changes in the remineralization depth of particulate organic and inorganic carbon (POC, PIC), a biogeochemical ocean circulation model (PISCES) was run with different parameterizations for vertical particle fluxes. On the basis of fluxes of POC and PIC, productivity, export, and the distributions of nitrogen (NO3), dissolved inorganic carbon (DIC), and alkalinity, a number of indices defined to estimate the efficiency of carbon transport away from the atmosphere are applied. With differing success for the respective indices the results show that the more efficient the vertical transport of organic carbon toward depth, the lower the surface ocean pCO2, the higher the air-sea CO2 flux, and the stronger the increase in the oceanic inventory of DIC. Along with POC flux it is important to consider variations in PIC flux, as the net effect of particle flux reorganizations on surface ocean pCO2 is a combination of changes in DIC and alkalinity. The results demonstrate that changes in the mechanistic formulation of vertical particle fluxes have direct and indirect effects on surface ocean pCO2 and may thus interact with the atmospheric CO2 reservoir.

  3. Temporal variation and stoichiometric ratios of organic matter remineralization in bottom waters of the northern Gulf of Mexico during late spring and summer

    NASA Astrophysics Data System (ADS)

    Xue, Jianhong; Cai, Wei-Jun; Hu, Xinping; Huang, Wei-Jen; Lohrenz, Steven E.; Gundersen, Kjell

    2015-12-01

    An improved extended optimum multiparameter (eOMP) analysis was applied to hydrographic (temperature and salinity), and water chemistry data, including dissolved oxygen (O2), nutrients (nitrate plus nitrite, phosphate, and silicate), dissolved inorganic carbon (DIC), and total alkalinity (TAlk) data collected during late spring and summer from 2006 to 2012 in bottom waters off the Louisiana coast, to explore the dynamics and stoichiometry of DIC production during the development and maintenance of summer hypoxia. Our analysis demonstrated that DIC in bottom water was relatively low from April to June, but increased significantly in July, peaked in August, and dropped slightly in September. Furthermore, DIC production resulted from both aerobic organic carbon (OC) respiration and denitrification, as well as substantial loss due to vertical mixing with surface water. The average summer gross OC respiration rate was estimated to be 0.19 g C m-2 d-1, with the highest values occurring in late summer when hypoxic conditions dominated. We also found that Corg/N/P/-O2 remineralization ratios for aerobic respiration were generally consistent with the classic Redfield ratio (106/16/1/138) except individual C/N and C/P ratios were slightly lower, indicating that marine OC was the major source of the DIC production in the bottom water. This study quantified the role of temporal bottom-water microbial respiration to seasonal DIC dynamics and provided a means for studying the stoichiometry of biogeochemical processes in coastal waters.

  4. Burial, remineralization and utilization of organic matter at the sea floor under a strong western boundary current. Final report, May 1, 1992--April 30, 1995

    SciTech Connect

    Jahnke, R.A.

    1995-08-24

    The overall goals of this project were to quantify the rates of organic carbon export from the southern mid-Atlantic Bight and to quantify the rates at which carbon is exchanged between the inorganic and organic pools within the bottom sediments. This information is necessary to constrain the role of the oceans in the control of carbon dioxide released to the atmosphere in association with energy production. During this project, in situ benthic flux chamber incubations have been performed at six sites on the continental slope and rise adjacent to Cape Hatteras. Based on the analysis of the time-series samples recovered during each experiment, the sea floor exchange rates of the major biogenic elements, oxygen, carbon, nitrogen, phosphorus and silicon were calculated. From the estimated benthic flux rates and the ancillary pore water and sediment analyses, the deposition, remineralization and burial rates of organic carbon to the sea floor in this area was evaluated. This information has been incorporated into regional and global assessments of organic carbon fluxes to the deep sea.

  5. Therapeutic efficacy of alternative primaquine regimens to standard treatment in preventing relapses by Plasmodium vivax

    PubMed Central

    Tamayo Perez, María-Eulalia; Aguirre-Acevedo, Daniel Camilo

    2015-01-01

    Objective: To compare efficacy and safety of primaquine regimens currently used to prevent relapses by P. vivax. Methods: A systematic review was carried out to identify clinical trials evaluating efficacy and safety to prevent malaria recurrences by P. vivax of primaquine regimen 0.5 mg/kg/ day for 7 or 14 days compared to standard regimen of 0.25 mg/kg/day for 14 days. Efficacy of primaquine according to cumulative incidence of recurrences after 28 days was determined. The overall relative risk with fixed-effects meta-analysis was estimated. Results: For the regimen 0.5 mg/kg/day/7 days were identified 7 studies, which showed an incidence of recurrence between 0% and 20% with follow-up 60-210 days; only 4 studies comparing with the standard regimen 0.25 mg/kg/day/14 days and no difference in recurrences between both regimens (RR= 0.977, 95% CI= 0.670 to 1.423) were found. 3 clinical trials using regimen 0.5 mg/kg/day/14 days with an incidence of recurrences between 1.8% and 18.0% during 330-365 days were identified; only one study comparing with the standard regimen (RR= 0.846, 95% CI= 0.484 to 1.477). High risk of bias and differences in handling of included studies were found. Conclusion: Available evidence is insufficient to determine whether currently PQ regimens used as alternative rather than standard treatment have better efficacy and safety in preventing relapse of P. vivax. Clinical trials are required to guide changes in treatment regimen of malaria vivax. PMID:26848199

  6. Iranian Low-dose Escalating Prophylaxis Regimen in Children with Severe Hemophilia A and B.

    PubMed

    Eshghi, Peyman; Sadeghi, Elham; Tara, S Zahra; Habibpanah, Behnaz; Hantooshzadeh, Razieh

    2017-01-01

    Establishing an appropriate prophylaxis regimen for children with hemophilia is a critical challenge in developing countries. Barriers including availability and affordability, catheter-related complications, and inhibitor development risks have led to the introduction of new tailored prophylaxis regimens in different countries. This study emphasizes on the benefits of the Iranian low-dose escalating prophylaxis regimen in a Hemophilia Comprehensive Care Center in Iran. Referred patients with hemophilia less than 15 years of age, who were subject to prophylaxis regimen, are studied retrospectively. A once-weekly prophylaxis regimen of 25 IU/kg was started for the patients primarily. Their prophylaxis regimen was changed to 25 IU/kg twice a week and then 3 times a week when they experienced 3 joint bleedings, 4 soft tissue bleedings, or a 1 life-threatening bleed without a specific trauma history. Overall, 25 patients with severe hemophilia and at least 6-month history of on-demand (OD) treatment were studied. A mean of 1754 IU/kg/yr of coagulation factors, used for OD and prophylaxis purposes, was sufficient to decrease the mean annual bleeding rate (ABR) to 1.86 after prophylaxis. It also reduced the mean hospitalization days and the mean number of target joints to 0.24 and 0.16, respectively. Overall, 19 (76%) patients were continuing their once-weekly regimen at the end of the follow-up. None of the patients needed 3-times-a-week regimen or central venous catheterization and none developed inhibitors in the follow-up. Benefits of the Iranian low-dose escalating prophylaxis regimen prove equal to some of the previous 3-times-a-week prophylaxis regimens in reducing the ABR and hospitalizations.

  7. Novel dosage forms and regimens for sevelamer-based phosphate binders.

    PubMed

    Duggal, Ajay; Hanus, Martin; Zhorov, Eugene; Dagher, Rafif; Plone, Melissa A; Goldberg, Jeffrey; Burke, Steven K

    2006-07-01

    Sevelamer, a nonabsorbed, calcium- and metal-free dietary phosphate binder, consists of a polyallylamine polymer backbone with a cationic charge that shows a high capacity for binding anionically charged compounds such as phosphate. The currently licensed form of sevelamer, Renagel, exists as sevelamer hydrochloride, which disassociates in the acidic environment of the stomach and early gastrointestinal tract, exchanging the chloride ions attached to the polymer backbone for phosphate ions. The resulting absorption of these chloride ions has been reported to be accompanied by a reduction in serum levels of bicarbonate in some patients. To minimize the possibility of this effect, a new salt form of sevelamer has been developed in which carbonate replaces the chloride counter ion, thereby providing a source of buffer. The majority of phosphate binders exist only in tablet form and are dosed three times per day with meals. Genzyme has developed sevelamer carbonate in tablet form and also as a powder formulation that can be taken after mixing with water. This allows for an alternate and potentially more palatable way of dosing. Preliminary data exist suggesting that once daily dosing with sevelamer hydrochloride tablets provides similar phosphate control to three times daily dosing. By providing novel dosage forms and regimens for sevelamer-based phosphate binders, Genzyme will be providing patients and health care providers additional choices and flexibility in controlling phosphorus levels in chronic kidney disease. This should translate to increased compliance and improved rates of phosphate control.

  8. The effect of commercial sterilization regimens on micellar casein concentrates.

    PubMed

    Beliciu, C M; Sauer, A; Moraru, C I

    2012-10-01

    This work focused on evaluating the effects of UHT sterilization and in-container retorting on the stability and physical properties of micellar casein concentrates (MCC). The study was performed on MCC obtained by membrane separation, with casein concentrations between 5 and 10%. The UHT and retorting regimens were designed to achieve the same microbial inactivation effect. Ultra-high temperature treatment was performed in a pilot-scale MicroThermics heating system (MicroThermics Inc., Raleigh, NC), and retorting in an FMC multipurpose laboratory retort (Steritort; FMC Corp., San Jose, CA). The heat-treated and the non-heat-treated MCC controls were evaluated for pH, mineral profile, ζ-potential, particle size, and rheological properties for up to 24h after heat treatment. The treatments were performed in triplicate, and differences among samples were evaluated using statistical analyses. Retorting resulted in slight aggregation in the MCC, whereas UHT caused the formation of visible aggregates and coagulation. The UHT-treated MCC had higher viscosity than retorted MCC, and displayed predominantly solid-like rheological behavior, indicative of structure formation. These effects were, at least in part, attributed to a change in mineral equilibrium, which affected the stability of the casein micelles, but additional mechanisms such as κ-casein dissociation may also play a significant role in these heat-induced changes. Drying of MCC accentuated the observed instabilities, as dried and reconstituted micellar casein concentrates (R-MCC) were more unstable to UHT sterilization than the MCC that had not undergone drying. The results of this study provide valuable information about the sterilization behavior and physical properties of MCC, which can be useful to processors in the development and manufacture of shelf-stable casein-based products and beverages.

  9. Patient compliance with crucial drug regimens: implications for prostate cancer.

    PubMed

    Urquhart, J

    1996-01-01

    Understanding of patient compliance with crucial drug regimens has improved markedly since 1986, based on data from two objective methods for monitoring drug dosing by ambulatory patients. Electronic monitoring records times and dates of drug package use, and chemical markers, incorporated into drug dosage forms, are assayed in plasma. These methods remove the camouflage that masks many poor compliers. In contrast, other methods (returned tablet counts, interviews, questionnaires) allow patients easily to censor evidence for delayed or omitted doses. The new methods show many more and larger errors of omission in both trials and practice than previously believed. One patient in about six is punctually compliant, but a modest majority of patients make errors probably too small to attenuate or otherwise modify the actions of all but the most unforgiving medicines. About a third of patients delay or omit many prescribed doses, thus attenuating or otherwise modifying the actions of all but the most forgiving drugs. One patient in about six takes little medicine, though camouflaged as a good complier. Similar patterns of delayed and omitted does prevail, essentially independent of drug, disease, prognosis, or symptoms. In summary, patients take the prescribed dose at intervals longer than prescribed--often by hours, sometimes by days, occasionally by weeks. The clinical and economic consequences of these lapses in dosing are unique to the treatment situation and the severity of disease and comorbidity. The new methods have not yet been applied to androgen-blocking agents, but if the findings resemble those with, e.g. tamoxifen in breast cancer, it will doubtless trigger some rethinking about failed treatment, trial design, and clinical management.

  10. Optimization of dosing regimens and dosing in special populations.

    PubMed

    Sime, F B; Roberts, M S; Roberts, J A

    2015-10-01

    Treatment of infectious diseases is becoming increasingly challenging with the emergence of less-susceptible organisms that are poorly responsive to existing antibiotic therapies, and the unpredictable pharmacokinetic alterations arising from complex pathophysiologic changes in some patient populations. In view of this fact, there has been a progressive work on novel dose optimization strategies to renew the utility of forgotten old antibiotics and to improve the efficacy of those currently in use. This review summarizes the different approaches of optimization of antibiotic dosing regimens and the special patient populations which may benefit most from these approaches. The existing methods are based on monitoring of antibiotic concentrations and/or use of clinical covariates. Measured concentrations can be correlated with predefined pharmacokinetic/pharmacodynamic targets to guide clinicians in predicting the necessary dose adjustment. Dosing nomograms are also available to relate observed concentrations or clinical covariates (e.g. creatinine clearance) with optimal dosing. More precise dose prediction based on observed covariates is possible through the application of population pharmacokinetic models. However, the most accurate estimation of individualized dosing requirements is achieved through Bayesian forecasting which utilizes both measured concentration and clinical covariates. Various software programs are emerging to ease clinical application. Whilst more studies are warranted to clarify the clinical outcomes associated with the different dose optimization approaches, severely ill patients in the course of marked infections and/or inflammation including those with sepsis, septic shock, severe trauma, burns injury, major surgery, febrile neutropenia, cystic fibrosis, organ dysfunction and obesity are those groups which may benefit most from individualized dosing.

  11. Differences in Lipid Measurements by Antiretroviral Regimen Exposure in Cohorts from Asia and Australia

    PubMed Central

    Achhra, Amit C.; Amin, Janaki; Hoy, Jennifer; Tanuma, Junko; Sirisanthana, Thira; Nolan, David; Merati, Tuti; Giles, Michelle

    2012-01-01

    We explored the mean differences in routinely measured lipids (total cholesterol, triglycerides, and high-density lipoprotein cholesterol) according to exposure to different combination antiretroviral regimens in Asian (n = 2051) and Australian (predominantly Caucasian, n = 794) cohorts. The regimen was defined as at least 3 antiretroviral drugs with at least 2 nucleoside-reverse transcriptases (NRTIs) and either of at least one protease inhibitor (PI) or non-nucleoside-reverse transcriptases (NNRTIs). We categorised cART regimens as: NRTIs as tenofovir based or not; NNRTIs as nevirapine or efavirenz (but not both); and PI as atazanavir based or not. We found that the impact of various antiretroviral regimens on lipids in Asian and Australian cohorts was only different by cohort for total cholesterol (P for interaction between regimen and cohort: <0.001) but not in case of other lipids (P for interaction: >0.05). The differences in total cholesterol were however small and unlikely to be of clinical significance. Overall, tenofovir with nevirapine or atazanavir was associated with the most favorable lipids, while the PI regimens without tenofovir and atazanavir were associated with least favorable lipids. We conclude that the impact of various ART regimens on lipids is largely similar in Asian and Australian cohorts and that the newer drugs such as tenofovir and atazanavir are likely to provide similar benefit in terms of lipid profiles in both populations. PMID:22675613

  12. In silico evaluation and exploration of antibiotic tuberculosis treatment regimens

    SciTech Connect

    Pienaar, Elsje; Dartois, Véronique; Linderman, Jennifer J.; Kirschner, Denise E.

    2015-11-14

    Improvement in tuberculosis treatment regimens requires selection of antibiotics and dosing schedules from a large design space of possibilities. Incomplete knowledge of antibiotic and host immune dynamics in tuberculosis granulomas impacts clinical trial design and success, and variations among clinical trials hamper side-by-side comparison of regimens. Our objective is to systematically evaluate the efficacy of isoniazid and rifampin regimens, and identify modifications to these antibiotics that improve treatment outcomes. We pair a spatio-temporal computational model of host immunity with pharmacokinetic and pharmacodynamic data on isoniazid and rifampin. The model is calibrated to plasma pharmacokinetic and granuloma bacterial load data from non-human primate models of tuberculosis and to tissue and granuloma measurements of isoniazid and rifampin in rabbit granulomas. We predict the efficacy of regimens containing different doses and frequencies of isoniazid and rifampin. We predict impacts of pharmacokinetic/pharmacodynamic modifications on antibiotic efficacy. We demonstrate that suboptimal antibiotic concentrations within granulomas lead to poor performance of intermittent regimens compared to daily regimens. Improvements from dose and frequency changes are limited by inherent antibiotic properties, and we propose that changes in intracellular accumulation ratios and antimicrobial activity would lead to the most significant improvements in treatment outcomes. Results suggest that an increased risk of drug resistance in fully intermittent as compared to daily regimens arises from higher bacterial population levels early during treatment. In conclusion, our systems pharmacology approach complements efforts to accelerate tuberculosis therapeutic development.

  13. A pilot phase II study of neoadjuvant triplet chemotherapy regimen in patients with locally advanced resectable colon cancer

    PubMed Central

    Zhou, Haitao; Song, Yan; Jiang, Jun; Niu, Haitao; Zhao, Hong; Liang, Jianwei; Su, Hao; Wang, Zheng; Zhou, Zhixiang; Huang, Jing

    2016-01-01

    Objective This study aims to investigate the feasibility, safety and efficacy of triplet regimen of neoadjuvant chemotherapy in patients with locally advanced resectable colon cancer. Methods Patients with clinical stage IIIb colon cancer received a perioperative triple chemotherapy regimen (oxaliplatin 85 mg/m2 and irinotecan 150 mg/m2, combined with folinic acid 200 mg, 5-fluorouracil 500 mg bolus and then 2,400 mg/m2 by 44 h infusion or capecitabine 1 g/m2 or S-1 40–60 mg b.i.d orally d 1–10, repeated at 2-week intervals) for 4 cycles. Complete mesocolic excision was scheduled 2–6 weeks after completion of neoadjuvant treatment and followed by a further 6 cycles of FOLFOXIRI or XELOX. Primary outcome measures of this stage II trial were feasibility, safety, tolerance and efficacy of neoadjuvant treatment. Results All 23 patients received neoadjuvant chemotherapy and underwent surgery. Twenty-one patients (91.3%) had reductions in tumor volume after neoadjuvant treatment, and 13 patients (56.5%) had grade 3–4 toxicity. No patients had severe complications from surgery. Preoperative therapy resulted in significant down-staging of T-stage and N-stage compared with the baseline clinical stage including one pathological complete response. Conclusions Neoadjuvant triple chemotherapy has high activity and acceptable toxicity and perioperative morbidity, and is feasible, tolerable and effective for locally advanced resectable colon cancer. PMID:28174488

  14. HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen.

    PubMed

    Cavaco-Silva, Joana; Abecasis, Ana; Miranda, Ana Cláudia; Poças, José; Narciso, Jorge; Águas, Maria João; Maltez, Fernando; Almeida, Isabel; Germano, Isabel; Diniz, António; Gonçalves, Maria de Fátima; Gomes, Perpétua; Cunha, Celso; Camacho, Ricardo Jorge

    2014-01-01

    To characterize the HIV-2 integrase gene polymorphisms and the pathways to resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied 63 integrase strand transfer inhibitors (INSTI)-naïve patients, and 10 heavily pretreated patients exhibiting virological failure while receiving a salvage raltegravir-containing regimen. All patients were infected by HIV-2 group A. 61.4% of the integrase residues were conserved, including the catalytic motif residues. No INSTI-major resistance mutations were detected in the virus population from naïve patients, but two amino acids that are secondary resistance mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10 patients). Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. Data retrieved from this study should help build a more robust HIV-2-specific algorithm for the genotypic interpretation of raltegravir resistance, and contribute to improve the clinical monitoring of HIV-2-infected patients.

  15. Evaluation of a single dose versus a divided dose regimen of amoxycillin in treatment of Actinobacillus pleuropneumoniae infection in pigs.

    PubMed

    Lauritzen, B; Lykkesfeldt, J; Friis, C

    2005-08-01

    The theory of a time-dependent effect of amoxycillin was examined in a model of porcine Actinobacillus pleuropneumoniae (Ap)-infection using clinically relevant dosage regimens. Twenty hours after infection of fourteen pigs, when clinical signs of pneumonia were present, one group of pigs received a single dose of amoxycillin (20 mg/kg, i.m.), whereas another group received four doses of 5 mg/kg injected at 8-h intervals. A similar AUC of the plasma amoxycillin concentration versus time curve was obtained in the two groups, whereas the maximum concentration was threefold higher using the single high dose. Plasma amoxycillin was above the MIC for twice as long using the fractionated dosage scheme. The condition of the animals was evaluated by clinical and haematological observations combined with quantification of biochemical infection markers: C-reactive protein, zinc and ascorbic acid. Within 48 h of treatment, the pigs in both treatment groups recovered clinically. No significant differences in the time-course of clinical observations or plasma concentrations of the biomarkers of infection were observed between the two treatments. In conclusion, the efficacy of these two dosage regimens of amoxycillin was not significantly different in treatment of acute Ap-infection in pigs.

  16. Weekly Moxifloxacin and Rifapentine Is More Active Than the Denver Regimen in Murine Tuberculosis

    PubMed Central

    Rosenthal, Ian M.; Williams, Kathy; Tyagi, Sandeep; Vernon, Andrew A.; Peloquin, Charles A.; Bishai, William R.; Grosset, Jacques H.; Nuermberger, Eric L.

    2005-01-01

    Rationale: Treatment of tuberculosis with an efficacious once-weekly regimen would be a significant achievement in improving patient adherence. Currently, the only recommended once-weekly continuation phase regimen of isoniazid plus rifapentine (10 mg/kg) is inferior to standard twice-weekly therapy with isoniazid plus rifampin and is, therefore, restricted to non–high-risk patients. The substitution of moxifloxacin, a new 8-methoxyfluoroquinolone, for isoniazid and an increase in the dose of rifapentine could augment the activity of once-weekly regimens. Methods: To test this hypothesis we evaluated the sterilizing activity of improved once-weekly rifapentine-based continuation phase regimens in a murine model that mimics the treatment of high-risk patients with tuberculosis. The bactericidal activity of standard daily therapy and standard intermittent therapy (“Denver” regimen) was also assessed to evaluate the effect of intermittent drug administration during the initial phase of therapy. Results: After 2 mo of treatment, lung colony-forming unit counts were 1 log10 lower in mice treated with standard daily therapy than with the Denver regimen. During the continuation phase, the sterilizing activity of once-weekly moxifloxacin plus rifapentine (15 mg/kg) was significantly greater than that of the predominantly twice-weekly Denver regimen of isoniazid plus rifampin. No significant difference in sterilizing activity was detected between once-weekly isoniazid plus rifapentine (15 mg/kg) and the Denver regimen. Conclusions: These results suggest that the efficacy of the once-weekly isoniazid plus rifapentine continuation phase regimen can be increased by substituting moxifloxacin for isoniazid and by increasing the dose of rifapentine to a clinically acceptable level of 15 mg/kg. PMID:16141439

  17. Congenital syphilis after treatment of maternal syphilis with a penicillin regimen exceeding CDC guidelines.

    PubMed Central

    Conover, C S; Rend, C A; Miller, G B; Schmid, G P

    1998-01-01

    BACKGROUND: Although congenital syphilis usually occurs as a result of a failure to detect and treat syphilis in pregnant women, failures of the currently recommended regimen to prevent congenital syphilis have been reported. CASE: This report describes an infant with congenital syphilis despite maternal treatment with a regimen exceeding current CDC guidelines. CONCLUSION: Regardless of the regimen used to treat syphilis during pregnancy, clinicians should recognize the possibility of occasional treatment failures and the importance of adequate follow-up of infants at risk for congenital syphilis. PMID:9785110

  18. Persistence to single-tablet regimen versus less-drug regimen in treatment experienced HIV-infected patients on antiretroviral therapy.

    PubMed

    Jiménez-Galán, Rocio; Cantudo Cuenca, Maria-Rosa; Robustillo-Cortés, María Aguas; Borrego Izquierdo, Y; Almeida-Gonzalez, Carmen Victoria; Morillo-Verdugo, Ramón

    2016-06-01

    Objetivos: Analizar y comparar la persistencia entre las estrategias basadas en Single-Tablet Regimen (STR) y Less Drug Regimen (LDR) en pacientes VIH+. El objetivo secundario del estudio fue determinar factores predictores de persistencia. Material y métodos: Estudio observacional retrospectivo que incluyo los siguientes criterios: pacientes VIH+ con tratamiento antirretroviral (TAR) con un regimen basado en STR o LDR. Se recogieron variables demograficas, factores de riesgo de adquisicion, consumo de drogas, presencia de algun trastorno psiquiatrico y coinfeccion por el virus de la hepatitis B o C. Para comparar la persistencia entre ambas estrategias se realizo un analisis de supervivencia de Kaplan-Meir y se aplico el metodo de log-rank. Se realizo un analisis de regresion de Cox para identificar los factores predictores de persistencia. Resultados: Se incluyeron 244 pacientes, 176 con STR y 68 con LDR. El 34,1% (n = 60) de los pacientes que recibieron un regimen STR abandonaron y en el LDR el 19,1% (n = 13). Los efectos adversos fueron la principal causa de abandono del tratamiento en los pacientes que recibieron STR y el fallo virologico en el regimen LDR. La persistencia de las estrategias STR y LDR fue similar, no encontrandose diferencias estadisticamente significativas entre ambas. El consumo de drogas fue el unico factor predictivo asociado con una menor persistencia (HR = 2,59; p = 0,005). Conclusiones: La persistencia entre los regimenes STR y LDR fue similar, no detectandose diferencias significativas entre ambos. El consumo de drogas fue el unico factor independiente asociado con una menor persistencia del tratamiento antirretroviral.

  19. Sensitivity of air-sea CO2-exchange and calcite saturation depth to the remineralization depth of marine particulate organic and inorganic carbon

    NASA Astrophysics Data System (ADS)

    Schneider, B.; Bopp, L.; Gehlen, M.

    2009-04-01

    The present study addresses the question of what would happen to air-sea CO2 exchange and the depth of the calcite saturation horizon (CSH) if the remineralization depth of particulate organic and inorganic carbon (POC, PIC) was changing. Therefore, a biogeochemical ocean circulation model (PISCES) was run with four different parameterizations for vertical particle fluxes, starting from the same initial conditions. Particle fluxes undergo strong changes induced by a combination of the respective mechanistic formulation of the vertical particle flux and the resulting ecosystem response. Reorganizations in dissolved properties are caused by (i) changed fluxes of POC and PIC; (ii) advection; (iii) air-sea CO2 exchange (DIC). The results show that the more (less) efficient the vertical transport of POC (PIC) from the surface toward depth, the lower the surface ocean pCO2, the higher the air-sea CO2 flux, and the stronger the increase in the oceanic inventory of DIC, and vice versa. Consequently, in one experiment the ocean is turning into a CO2 source to the atmosphere, in two cases it becomes a weak sink and in one simulation it turns into a strong sink. Surprisingly, results for changes in the CSH are more similar among the simulations at larger scale with a general deepening in the North Pacific and a shoaling elsewhere. In most areas the readjustment of the CSH is controlled by DIC and alkalinity acting both towards the simulated CSH shifts, however, in some cases DIC (alkalinity) is overcompensating for an effect that would occur due to changes in alkalinity (DIC), alone. In detail, the differences found between the experiments can be well explained by the respective particle flux responses. The current study shows that reorganizations in the vertical flux of particulate matter in the ocean may have immediate and longer-term effects on the marine carbon cycle which could potentially feedback on the climate system.

  20. Examining the impact of grazing on iron remineralization: effect of prey type on digestive vacuole pH

    NASA Astrophysics Data System (ADS)

    Pritchard, K. R.; Nuester, J.; Twining, B.

    2012-12-01

    Most of the iron available to phytoplankton in high-nutrient, low-chlorophyll areas is regenerated by zooplankton grazers. The extent to which the bioavailability of this regenerated iron is a function of prey-type and the chemical conditions within digestive systems of zooplankton is unknown. The chemical composition of the prey, including silica frustules of diatoms and calcium carbonate coccoliths of cocolithophores, might buffer the acidity within a digestive vacuole and thereby influencing the resulting speciation and bioavailability of regenerated iron. In order to test the effect of prey-type on the chemical condition in the digestive vacuole of the heterotrophic dinoflagellate Oxyrrhis marina, we used the ratiometric fluorescent dye Lysosensor Yellow/Blue DND-160 in conjunction with confocal microscopy to measure and compare digestive vacuole acidity after feeding O. marina with either the diatom Thalassiosira pseudonana, the coccolithophore Emiliana huxleyi, or the chlorophyte Dunaliella tertiolecta. After feeding and loading O. marina with the Lysosensor dye, we recorded the total fluorescence (f) of the wavelength regions λ1=500-555 nm and λ2=410-490 nm using an excitation wavelength of 405 nm, and calculated the Lysosensor fluorescence ratio r=f(λ1)/f(λ2). External calibration curves show that this ratio (r) is inversely related to pH. In addition, we also measured the emission of chlorophyll fluorescence above 640 nm in order to identify prey within the grazers and study the timing chlorophyll degradation in conjunction with vacuole pH. After the initial addition of either prey, O. marina consumed 10 times and 2 times more D. tertiolecta cells than E. huxleyi and T. pseudonana cells, respectively. The clearance of the digestive vacuole measured as the disappearance of chlorophyll fluorescence is ca. twice as long for O. marina feeding on D. tertiolecta than on E. huxleyi or T. pseudonana. Initial r was inversely proportional to prey preference

  1. Priority-Setting for Novel Drug Regimens to Treat Tuberculosis: An Epidemiologic Model

    PubMed Central

    Cohen, Ted; Nuermberger, Eric; Dooley, Kelly E.; Gonzalez-Angulo, Lice; Churchyard, Gavin J.; Nahid, Payam; Rich, Michael L.; Bansbach, Cathy; Forissier, Thomas; Dowdy, David W.

    2017-01-01

    Background Novel drug regimens are needed for tuberculosis (TB) treatment. New regimens aim to improve on characteristics such as duration, efficacy, and safety profile, but no single regimen is likely to be ideal in all respects. By linking these regimen characteristics to a novel regimen’s ability to reduce TB incidence and mortality, we sought to prioritize regimen characteristics from a population-level perspective. Methods and Findings We developed a dynamic transmission model of multi-strain TB epidemics in hypothetical populations reflective of the epidemiological situations in India (primary analysis), South Africa, the Philippines, and Brazil. We modeled the introduction of various novel rifampicin-susceptible (RS) or rifampicin-resistant (RR) TB regimens that differed on six characteristics, identified in consultation with a team of global experts: (1) efficacy, (2) duration, (3) ease of adherence, (4) medical contraindications, (5) barrier to resistance, and (6) baseline prevalence of resistance to the novel regimen. We compared scale-up of these regimens to a baseline reflective of continued standard of care. For our primary analysis situated in India, our model generated baseline TB incidence and mortality of 157 (95% uncertainty range [UR]: 113–187) and 16 (95% UR: 9–23) per 100,000 per year at the time of novel regimen introduction and RR TB incidence and mortality of 6 (95% UR: 4–10) and 0.6 (95% UR: 0.3–1.1) per 100,000 per year. An optimal RS TB regimen was projected to reduce 10-y TB incidence and mortality in the India-like scenario by 12% (95% UR: 6%–20%) and 11% (95% UR: 6%–20%), respectively, compared to current-care projections. An optimal RR TB regimen reduced RR TB incidence by an estimated 32% (95% UR: 18%–46%) and RR TB mortality by 30% (95% UR: 18%–44%). Efficacy was the greatest determinant of impact; compared to a novel regimen meeting all minimal targets only, increasing RS TB treatment efficacy from 94% to 99

  2. Fewer doses of HPV vaccine result in immune response similar to three-dose regimen

    Cancer.gov

    NCI scientists report that two doses of a human papillomavirus (HPV) vaccine, trademarked as Cervarix, resulted in similar serum antibody levels against two of the most carcinogenic types of HPV (16 and 18), compared to a standard three dose regimen.

  3. Successful intraoperative spinal cord monitoring during scoliosis surgery using a total intravenous anesthetic regimen including dexmedetomidine.

    PubMed

    Anschel, David J; Aherne, Andrew; Soto, Roy G; Carrion, Wesley; Hoegerl, Carl; Nori, Palgun; Seidman, Peggy A

    2008-02-01

    Intraoperative neurophysiological monitoring (IONM) during corrective spinal surgery is widely used. Because of the possible interference with the recording of evoked potentials by inhalational anesthetics, total intravenous anesthetic (TIVA) regimens have been advocated. TIVA regimens may be difficult to use in pediatric populations due to metabolic factors. We report on the results of multimodality IONM during 18 cases in which a TIVA regimen incorporating dexmedetomidine (Precedex, Hespira, Lake Forest, IL) was used. Monitoring techniques included sensory (SSEP) and motor evoked potentials (MEP), as well as pedicle screw stimulation. SSEPs were maintained within an acceptable range of baseline amplitude (50%) and latency (10%), and MEPs remained elicitable throughout each case. We therefore found that the anesthetic regimen did not significantly interfere with any of the monitoring modalities used and conclude that IONM in the presence of dexmedetomidine is feasible under appropriate conditions.

  4. Efficacy and Optimization of Palivizumab Injection Regimens Against Respiratory Syncytial Virus Infection

    PubMed Central

    Gutfraind, Alexander; Galvani, Alison P.; Meyers, Lauren Ancel

    2015-01-01

    IMPORTANCE Infection with the respiratory syncytial virus (RSV) is the leading cause of hospitalizations in children, accounting for more than 90 000 hospitalizations every year in the United States. For children who are at risk for severe RSV infections, the American Academy of Pediatrics recommends immunoprophylaxis with a series of up to 5 injections of the antibody palivizumab administered monthly, beginning on November 1 of each year. However, many practitioners initiate injections at the onset of RSV season as indicated by local surveillance. OBJECTIVES To evaluate the effectiveness of current regimens for palivizumab injections across different cities and to design an optimized regimen. DESIGN, SETTING, AND PARTICIPANTS We performed a mathematical modeling study of the risk for hospitalization due to RSV infection. The model accounted for the pharmacokinetics of the antibody, the timing of the injections, and seasonal patterns of RSV, including geographic and year-to-year variability. We used the model to estimate the efficacy of current regimens, including the American Academy of Pediatrics recommendation, and to design a more effective injection regimen, the optimized fixed start (OFS), which uses city-specific initiation dates. Participants were the approximately 700 000 individuals who had specimens tested for RSV by National Respiratory and Enteric Virus Surveillance System laboratories in 18 US cities from July 1, 1994, through June 30, 2011 (a total of 725 741 tests). INTERVENTIONS Different palivizumab injection regimens. MAIN OUTCOMES AND MEASURES The primary outcome measure was reduction in hospitalizations due to RSV infections. The secondary measures were cost (number of palivizumab doses) and duration of protection (in days). RESULTS The American Academy of Pediatrics–recommended 5-injection regimen is expected to reduce hospitalization risk by a median of 2.7% (range, −2.2% to 6.1%) compared with the conventional regimen based on RSV

  5. Isoniazid or Moxifloxacin in Rifapentine-based Regimens for Experimental Tuberculosis?

    PubMed Central

    Rosenthal, Ian M.; Zhang, Ming; Almeida, Deepak; Grosset, Jacques H.; Nuermberger, Eric L.

    2008-01-01

    Rationale: Recent studies have demonstrated that combined substitutions of rifapentine for rifampin and moxifloxacin for isoniazid in the standard, daily, short-course regimen of rifampin, isoniazid, and pyrazinamide produces stable cure in 12 weeks or less. This study was designed to more precisely evaluate the contribution of moxifloxacin and isoniazid to rifapentine-based regimens. Objectives: We compared bactericidal activity and treatment-shortening potential between regimens consisting of isoniazid or moxifloxacin plus rifapentine and pyrazinamide administered either thrice-weekly or daily. Methods: Using a mouse model of tuberculosis, we assessed bactericidal activity by performing quantitative cultures of lung homogenates over the first 12 weeks of treatment. Relapse rates were assessed after completing 8, 10, and 12 weeks of treatment to determine the duration of treatment necessary for stable cure. Measurements and Main Results: After 4 weeks of treatment, daily and thrice-weekly therapy with rifapentine, moxifloxacin, and pyrazinamide was significantly more active than treatment with rifapentine, isoniazid, and pyrazinamide. By 8 weeks of treatment, all mice receiving the moxifloxacin-containing regimens were lung culture negative, whereas those mice receiving the isoniazid-containing regimens continued to be lung culture positive. However, the duration of treatment necessary to achieve stable cure was 10 weeks for daily regimens and 12 weeks for thrice-weekly regimens, regardless of whether isoniazid or moxifloxacin was used. All mice receiving standard daily therapy with rifampin, isoniazid, and pyrazinamide relapsed after 12 weeks of treatment. Conclusions: These results suggest that regimens consisting of isoniazid or moxifloxacin plus rifapentine and pyrazinamide may dramatically shorten the duration of treatment needed to cure human tuberculosis. PMID:18723432

  6. Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson's Disease.

    PubMed

    Yun, Ji Young; Kim, Young Eun; Yang, Hui-Jun; Kim, Han-Joon; Jeon, Beomseok

    2017-01-01

    This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson's disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson's disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov.

  7. Cost description of chemotherapy regimens for the treatment of metastatic pancreas cancer.

    PubMed

    Goldstein, Daniel A; Krishna, Kavya; Flowers, Christopher R; El-Rayes, Bassel F; Bekaii-Saab, Tanios; Noonan, Anne M

    2016-05-01

    Multiple chemotherapy regimens are available for the treatment of metastatic pancreas cancer (mPCA). Choice of regimen is based on the patient's performance status and toxicity profile of the regimen. The objective of this study was to analyze the costs of first-line regimens to further aid in decision-making and develop a platform upon which to assess value. We calculated the monthly cost for individual standard regimens (gemcitabine, gemcitabine/nab-paclitaxel, gemcitabine/erlotinib and FOLFIRINOX) and the overall treatment cost for a course of therapy based on the median progression-free survival achieved in published studies. In addition to cost of drugs, we included administration costs and costs of toxicities (including growth factor support, blood product transfusion and hospitalization for toxicities). Costs for administration and management of adverse events were based on Medicare reimbursement rates for hospital and physician services. Drug costs were based on Medicare average sale prices (all 2014 US$). The monthly costs for gemcitabine, FOLFIRINOX, gemcitabine/erlotinib and gemcitabine/nab-paclitaxel were $1363, $7234, $8007 and $12,221, respectively. The overall treatment costs for a course of the same regimens based on median PFS were $5043, $46,298, $51,004 and $67,216, respectively. The choice of chemotherapy regimen for mPCA should be based on tolerability and efficacy of the regimen individualized to patient's performance status. Healthcare systems have finite resources; thus, there is increasing emphasis on metrics to define value in health care when outcomes of therapy are similar or produce marked differences in value. These data provide useful financial information to incorporate into the decision-making process.

  8. Dietary regimens of athletes competing at the Delhi 2010 Commonwealth Games.

    PubMed

    Pelly, Fiona E; Burkhart, Sarah J

    2014-02-01

    The aim of this study was to investigate the dietary regimens reported by athletes competing at a major international competition and report whether these were based on nutrient composition, religious beliefs, cultural eating style, food intolerance or avoidance of certain ingredients. A questionnaire was randomly distributed to 351 athletes in the main dining hall of the athletes' village over the three main meal periods during the Delhi 2010 Commonwealth Games (23rd Sept-14th Oct, 2010). The majority (n = 218, 62%) of athletes reported following one or more dietary regimens, with 50% (n = 174) following a diet based on the nutrient composition of the food. Significantly more athletes from weight category and aesthetic sports (28%, p = .005) and from power/sprint sports (41%, p = .004) followed low fat and high protein regimens respectively. Other specialized dietary regimens were followed by 33% of participants, with avoidance of red meat (13%), vegetarian (7%), Halal (6%), and low lactose regimens (5%) reported most frequently. Significantly more athletes from non-Western regions followed a vegetarian diet (p < .001), while more vegetarians reported avoiding additives (p = .013) and wheat (p ≤ .001). A Western style of eating was the most commonly reported cultural regimen (72% of total with 23% from non-Western regions). Those following a Western diet were significantly more likely to report following a regimen based on nutrient composition (p = .02). As a high proportion of athletes from differing countries and sports follow specialized dietary regimens, caterers and organizers should ensure that adequate nutrition support and food items are available at similar events.

  9. Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson's Disease

    PubMed Central

    Kim, Young Eun; Yang, Hui-Jun; Kim, Han-Joon

    2017-01-01

    This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson's disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson's disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov. PMID:28265478

  10. Altering Antimalarial Drug Regimens May Dramatically Enhance and Restore Drug Effectiveness

    PubMed Central

    Hastings, Ian M.

    2015-01-01

    There is considerable concern that malaria parasites are starting to evolve resistance to the current generation of antimalarial drugs, the artemisinin-based combination therapies (ACTs). We use pharmacological modeling to investigate changes in ACT effectiveness likely to occur if current regimens are extended from 3 to 5 days or, alternatively, given twice daily over 3 days. We show that the pharmacology of artemisinins allows both regimen changes to substantially increase the artemisinin killing rate. Malaria patients rarely contain more than 1012 parasites, while the standard dosing regimens allow approximately 1 in 1010 parasites to survive artemisinin treatment. Parasite survival falls dramatically, to around 1 in 1017 parasites if the dose is extended or split; theoretically, this increase in drug killing appears to be more than sufficient to restore failing ACT efficacy. One of the most widely used dosing regimens, artemether-lumefantrine, already successfully employs a twice-daily dosing regimen, and we argue that twice-daily dosing should be incorporated into all ACT regimen design considerations as a simple and effective way of ensuring the continued long-term effectiveness of ACTs. PMID:26239993

  11. Interferon-free regimens in patients with hepatitis C infection and renal dysfunction or kidney transplantation

    PubMed Central

    Cholongitas, Evangelos; Pipili, Chrysoula; Papatheodoridis, George V

    2017-01-01

    Treatment of patients with chronic kidney disease (CKD) and chronic hepatitis C (CHC) differs from that used in the general CHC population mostly when glomerular filtration rate (GFR) is below 30 mL/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile. In this setting, especially in the presence of advanced liver disease, sofosbuvir-based regimens are often used, despite sofosbuvir contraindication. It seems to have good overall safety with only 6% or 3.4% of CKD patients to discontinue therapy or develop serious adverse events without drug discontinuation. In addition, sustained virological response (SVR) rates with sofosbuvir based regimens in CKD patients appear to be comparable with SVR rates in patients with normal renal function. Treatment recommendations for kidney transplant recipients are the same with those for patients with CHC, taking into consideration potential drug-drug interactions and baseline GFR before treatment initiation. This review summarizes recent data on the current management of CHC in CKD patients highlighting their strengths and weaknesses and determining their usefulness in clinical practice. PMID:28217256

  12. Temperature induced decoupling of enzymatic hydrolysis and carbon remineralization in long-term incubations of Arctic and temperate sediments

    NASA Astrophysics Data System (ADS)

    Robador, Alberto; Brüchert, Volker; Steen, Andrew D.; Arnosti, Carol

    2010-04-01

    Extracellular enzymatic hydrolysis of high-molecular weight organic matter is the initial step in sedimentary organic carbon degradation and is often regarded as the rate-limiting step. Temperature effects on enzyme activities may therefore exert an indirect control on carbon mineralization. We explored the temperature sensitivity of enzymatic hydrolysis and its connection to subsequent steps in anoxic organic carbon degradation in long-term incubations of sediments from the Arctic and the North Sea. These sediments were incubated under anaerobic conditions for 24 months at temperatures of 0, 10, and 20 °C. The short-term temperature response of the active microbial community was tested in temperature gradient block incubations. The temperature optimum of extracellular enzymatic hydrolysis, as measured with a polysaccharide (chondroitin sulfate), differed between Arctic and temperate habitats by about 8-13 °C in fresh sediments and in sediments incubated for 24 months. In both Arctic and temperate sediments, the temperature response of chondroitin sulfate hydrolysis was initially similar to that of sulfate reduction. After 24 months, however, hydrolysis outpaced sulfate reduction rates, as demonstrated by increased concentrations of dissolved organic carbon (DOC) and total dissolved carbohydrates. This effect was stronger at higher incubation temperatures, particularly in the Arctic sediments. In all experiments, concentrations of volatile fatty acids (VFA) were low, indicating tight coupling between VFA production and consumption. Together, these data indicate that long-term incubation at elevated temperatures led to increased decoupling of hydrolytic DOC production relative to fermentation. Temperature increases in marine sedimentary environments may thus significantly affect the downstream carbon mineralization and lead to the increased formation of refractory DOC.

  13. Thalidomide-based induction regimens are as effective as bortezomib-based regimens in elderly patients with multiple myeloma with cereblon expression.

    PubMed

    Jung, Sung-Hoon; Choi, Hyun-Jung; Shin, Myung-Geun; Lee, Seung-Shin; Hwang, Eu Chang; Jung, Tae-Young; Cho, Min-Seok; Yang, Deok-Hwan; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Kim, Hyeoung-Joon; Lee, Je-Jung

    2016-10-01

    Cereblon (CRBN) has been identified as a primary target of immunomodulatory drugs and is considered a biomarker for the prediction of outcomes after thalidomide- or lenalidomide-based treatments. In this study, we evaluated CRBN expression in bone marrow (BM) tissue at diagnosis and investigated the relationship between CRBN expression and treatment outcomes after thalidomide- or bortezomib-based front-line therapies in 89 elderly patients with multiple myeloma (MM). CRBN expression at the time of diagnosis was evaluated with immunohistochemical (IHC) staining for myeloma cells in paraffin wax-embedded BM tissue. CRBN-immunostained slides were scored by intensity and diffuseness, and a total score of >6 was defined as CRBN-positive (CRBN(+)). Thirty-eight patients (45.2 %) were CRBN(+). Among patients treated with thalidomide-based regimens, CRBN(+) patients showed a better treatment response than did CRBN-negative patients (35.0 vs. 11.8 % complete response rate, respectively; HR = 4.038, P = 0.137). During a median follow-up of 31.8 months, patients treated with bortezomib-based regimens had a longer time to progression (TTP) than did patients treated with thalidomide-based regimens (15.6 vs. 13.2 months, respectively; P = 0.047), but early mortality occurred frequently in patients treated with bortezomib-based regimens. Additionally, there was no significant difference in survival outcomes between thalidomide- and bortezomib-based regimens in CRBN(+) patients (median TTP, 13.8 vs. 15.6 months, respectively; P = 0.842 and median OS, 39.3 vs. 30.1 months, respectively; P = 0.074). These data suggest that thalidomide-based regimens are as effective as bortezomib-based regimens in elderly patients with MM who are CRBN(+). Thus, CRBN positivity, by IHC staining, may be useful in deciding appropriate treatment options in elderly patients with MM.

  14. Comparative Impact of Suppressive Antiretroviral Regimens on the CD4/CD8 T-Cell Ratio

    PubMed Central

    Masiá, Mar; Padilla, Sergio; Barber, Xavier; Sanchis, Marina; Terol, Gertrudis; Lidón, Fernando; Gutiérrez, Félix

    2016-01-01

    Abstract Although different factors have been implicated in the CD4/CD8 T-cell ratio recovery in HIV-infected patients who receive effective antiretroviral therapy (ART), limited information exists on the influence of the regimen composition. A longitudinal study carried out in a prospective, single-center cohort of HIV-infected patients. ART regimens including non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), or integrase strand transfer inhibitors (INSTI) from patients who achieved long-term (≥6-month duration) virological suppression (HIV-RNA < 400 copies/mL) from January 1998 to June 2014 were analyzed. The impact of ART composition on the changes of the CD4/CD8 T-cell ratio was modeled using a mixed linear approach with adjustment for possible confounders. A total of 1068 ART regimens from 570 patients were analyzed. Mean (SD) age of the patients was 42.15 (10.68) years and 276 (48.42%) had hepatitis C virus (HCV) coinfection. Five hundred fifty-eight (52.25%) regimens were PI-based, 439 (40.10%) NNRTI-based, and 71 (6.65%) INSTI-based; 487 (45.60%) were initial regimens, 476 (44.57%) simplification, and 105 (9.83%) salvage regimens. Median (IQR) number of regimens was 1 (1–2) per patient, of 29 (14–58) months duration, and 4 (3–7) CD4/CD8 measurements per regimen. The median baseline CD4/CD8 ratio was 0.42, 0.50, and 0.54, respectively, with the PI-, NNRTI-, and INSTI-based regimens (P = 0.0073). Overall median (IQR) increase of CD4/CD8 ratio was 0.0245 (−0.0352–0.0690) per year, and a CD4/CD8 ratio ≥1 was achieved in 19.35% of the cases with PI-based, 25.97% with NNRTI-based, and 22.54% with INSTI-based regimens (P = 0.1406). In the adjusted model, the mean CD4/CD8 T-cell ratio increase was higher with NNRTI-based regimens compared for PI-based (estimated coefficient for PI [95% CI], −0.0912 [−0.1604 to −0.0219], P = 0.009). Also, a higher CD4/CD8 baseline ratio was associated with higher

  15. [Clinical curative efficacy of inducing remission for the newly diagnosed aged AML patients by chemotherapy with IA and DA regimens].

    PubMed

    Tian, Dong-Hua; Gan, Si-Lin; Xing, Hai-Zhou; Liu, Yan-Fang; Xie, Xin-Sheng; Sun, Hui

    2014-10-01

    This study was aimed to explore the clinical efficacy and toxicity of idarubicin (IA regimen) and daunoru-bicin combined with cytarabine (DA regimen) for treating aged patients with AML as induction chemotherapy. The clinical data of 60 newly diagnosed AML aged patients treated with IA or DA regimen were analyzed retrospectively. IA regimen group included 22 patients (8 male and 14 females with median age of 66 yrs), while the DA regimen group included 38 patients (20 males and 18 females with median age of 64 yrs). The complete remission rate, total effective rate and adverse effects after one chemotherapy course were compared. The results showed that the CR rate in IA regimen group was 63.63%, which was significantly higer than that in DA regimen group (31.58%) (P < 0.05). The total effective rate was 63.63% and 36.84% respectively in IA and DA regimen groups, there was significant difference between the two groups (P < 0.05). Both the hematological and non-hematological adverse effects were observed and no difference was found in the two regimen groups, neither in myelosupression (P > 0.05), the major hematological adverse effects, nor in non-hematological adverse effects (P > 0.05). It is concluded that for aged AML patients, IA regimen can achieve a higher CR rate and higher total effective rate than that in DA regimen without increase of adverse effects after one induction chemotherapy course.

  16. Improvement in morning hyperglycaemia with basal human ultratard and prandial human actrapid insulin--a comparison of multiple injection regimens.

    PubMed

    Davies, R R; McEwen, J; Moreland, T A; Durnin, C; Newton, R W

    1988-10-01

    Three 'pen'-administered multiple injection regimens have been compared with twice daily insulin injection regimens by means of 24-h profiles of plasma glucose and free insulin concentrations. Ten Type 1 diabetic patients received their usual twice daily insulin regimen and were then randomized to receive the same total daily insulin dose in four divided doses using (1) 50:50 premixed soluble and isophane, (2) 30:70 premixed soluble and isophane, and (3) preprandial soluble and evening crystalline-zinc insulins. Profiles were performed after 1 week on each regimen. Plasma glucose concentrations were similar during the twice daily regimen and the two premixed regimens, rising during the early hours of the morning to a peak between 0900 and 0930 h of 13.8 +/- 2.8 (+/- SD) mmol l-1 on the twice daily regimen, 13.6 +/- 5.3 mmol l-1 on the premixed 50:50 regimen, and 13.5 +/- 4.2 mmol-1 on the premixed 30:70 regimen. With the basal and prandial regimen, overnight plasma glucose concentrations were higher than with the other regimens between 2400 and 0300 h (p less than 0.05). Concentrations then fell until breakfast, and rose after this meal to a peak of 9.5 +/- 4.3 mmol l-1 (p less than 0.01). Mean plasma glucose concentrations were significantly lower than on the other three regimens between 0830 and 1100 h (p less than 0.05). Less variability was observed in 24-h mean plasma glucose concentrations during the basal and prandial regimen than during the other three regimens.

  17. Bioavailability of the Yuzpe and levonorgestrel regimens of emergency contraception: vaginal vs. oral administration.

    PubMed

    Kives, Sari; Hahn, Philip M; White, Emily; Stanczyk, Frank Z; Reid, Robert L

    2005-03-01

    Separate crossover studies compared the bioavailability of oral vs. vaginal routes of administration for the Yuzpe (n=5) and levonorgestrel regimens (n=4) of emergency contraception. Twice the standard dose of the Yuzpe regimen (200 microg of ethinyl estradiol, 1000 microg of levonorgestrel) or the levonorgestrel regimen (1500 microg of levonorgestrel) was self-administered vaginally. One week later, each subject received orally the standard dose of the assigned medication. Serial blood samples were collected over 24 h and assayed for levonorgestrel and ethinyl estradiol (for the Yuzpe regimen only). Paired t tests were used to compare oral vs. vaginal administration for maximum concentration (Cmax), time to maximum concentration (Tmax) and area under the curve over 24 h (AUC0-24). Relative bioavailability (vaginal/oral) was derived from AUC0-24. Vaginal administration of double the standard dose of the Yuzpe regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=14.6 ng/mL, p=.038) and a later Tmax (5.9 vs. 2.0 h, p=.066) for levonorgestrel, compared to oral administration. Corresponding ethinyl estradiol concentrations were higher (786 vs. 391 pg/mL, p=.039) and peaked later (4.0 vs. 1.9 hr, p=.154) with vaginal administration. Relative bioavailabilities for levonorgestrel and ethinyl estradiol were 58% and 175%, respectively. Similarly, vaginal administration of the levonorgestrel regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=15.2 ng/mL, p=.006) and a later Tmax (7.4 vs. 1.3 h, p=.037) for levonorgestel, compared to oral administration. The relative bioavailability was 62%. Our preliminary data suggest that vaginal administration of these emergency contraception regimens appears to require at least three times the standard oral dose to achieve equivalent systemic levonorgestrel concentrations.

  18. Sterilizing Activity of Fully Oral Intermittent Regimens against Mycobacterium Ulcerans Infection in Mice

    PubMed Central

    Robert, Jérôme; Veziris, Nicolas; Aubry, Alexandra; Jarlier, Vincent

    2016-01-01

    Background The treatment of Buruli ulcer (BU) that is caused by Mycobacterium ulcerans, is currently based on a daily administration of rifampin and streptomycin (RIF-STR). A fully oral intermittent regimen would greatly simplify its treatment on the field. Methodology/Principal findings The objective of this study was to assess the bactericidal and sterilizing activities of intermittent oral regimens in a murine model of established M. ulcerans infection. Regimens combining rifapentine (RFP 20 mg/kg) with either moxifloxacin (MXF 200 mg/kg), clarithromycin (CLR 100 mg/kg) or bedaquiline (BDQ 25 mg/kg) were administrated twice (2/7) or three (only for RFP-CLR 3/7) times weekly during 8 weeks. The bactericidal but also the sterilizing activities of these four intermittent oral regimens were at least as good as those obtained with control weekdays regimens, i.e. RFP-CLR 5/7 or RIF-STR 5/7. A single mouse from the RFP-MFX 2/7 group had culture-positive relapse at the end of the 28 weeks following treatment completion among the 157 mice treated with one of the four intermittent regimens (40 RFP-CLR 2/7, 39 RFP-CLR 3/7, 39 RFP-MXF 2/7, 39 RFP-BDQ 2/7). Conclusions/Significance These results open the door for a fully intermittent oral drug regimen for BU treatment avoiding intramuscular injections and facilitating supervision by health care workers. PMID:27755552

  19. Effect of light/dark regimen on N-nitrosoethylurea-induced transplacental carcinogenesis in rats.

    PubMed

    Beniashvili, D S; Benjamin, S; Baturin, D A; Anisimov, V N

    2001-02-10

    Pregnant females were randomly subdivided into three groups (24 rats per group) and kept at the 12:12 h light/dark regimen (group 1), at the constant light illumination (24 h a day, group 2) or at the continuous darkness (group 3). N-nitrosoethylurea (NEU) has been injected into the tail vein of all rats (80 mg/kg) on the 18-19th day of the pregnancy. After the delivery the lacting dams and their progeny during the lactation period (1 month after delivery) were kept also at the three different light/dark regimens. Then all offspring from each group was kept at the 12:12 h light/dark regimen, males and females separately, and were observed until natural death. The exposure to constant light significantly promoted the transplacental carcinogenesis whereas the exposure to constant darkness inhibited it. The incidence of total tumors, tumors of both a peripheral nervous system and kidney was 2.6; 2.5 and 8.5 times higher, and survival significantly shorter, correspondingly, in rats from the group 2 exposed to the constant light regimen as compared to the group 1 (12:12 h light/dark regimen) (P<0.05). On the other hand, the exposure to the continuous darkness during the pregnancy and the lactation period significantly inhibited the transplacental carcinogenesis in the offspring of rats treated with NEU. The incidence of total tumors, tumors of a peripheral nervous system was by 2.4 and 2.7 times less, and survival longer, respectively, in exposed to the darkness rats from the group 3 as compared to the group 1 (12:12 h light/dark regimen) (P<0.05). Thus, our data firstly have shown the modifying effect of light-dark regimen on the realization of the transplacental carcinogenesis induced by NEU in rats.

  20. Effects of different temperature regimens on the development of Aedes aegypti (L.) (Diptera: Culicidae) mosquitoes.

    PubMed

    Mohammed, Azad; Chadee, Dave D

    2011-07-01

    This study was conducted to determine the effects of increased water temperatures on the development of Aedes aegypti immatures under laboratory conditions in Trinidad, West Indies using temperature regulated water baths to cover a range of temperatures from 24-25°C to 34-35°C at a relative humidity of 80%. Two experiments were designed: (1) at constant temperature regimens and (2) under diurnal temperature regimens ranging from 24-25°C to 34-35°C. At 24-25°C egg hatching success was 98% at 48 h, however at 34-35°C egg hatching rates declined to 1.6% after 48 h. Ae. aegypti larvae reared under constant temperature regimens showed pupation on day 4 with highest pupation occurring at 30°C (78.4%) However, under diurnal temperature regimens, pupation began on day 4 but only at the higher temperatures of 30-35°C. Under diurnal temperature regimens ranging from 24°C to 35°C significantly more females emerged at higher temperatures, than males. In contrast, at constant temperatures of 24-35°C no significant difference in M/F ratios were observed. The body size of Ae. aegypti reared at constant temperature regimens was significantly larger than males and females larvae reared under diurnal temperature regimens of 25-30°C. The results of this study are discussed in the context of changing or increasing water temperatures, seasonal changes in vector populations and vector competence. Using these key factors control strategies are recommended to manage vector populations as expected increases in temperatures impact the Caribbean region.

  1. Comparison between the effects of one-day treatment regimen with cisplatin on renal function and various biochemical parameters in patients with gastric and lung cancer compared with two-days divided cisplatin treatment regimen

    PubMed Central

    Ahmadzadeh, Ahmad; Shahbazian, Heshmatollah; Safapour, Neda; Tulabi, Mehri; Zandifar, Sepideh

    2015-01-01

    Introduction: Cisplatin is an efficient chemotherapeutic drug used for the treatment of different cancers. Clinical trials represents cisplatin-induced nephrotoxicity in a dose dependent manner. Objectives: This study aimed to compare the effects of 1-day treatment regimen with cisplatin on renal function, potassium, calcium, magnesium and uric acid in patients with gastric and lung cancer compared with 2-day divided cisplatin treatment regimen to suggest appropriate management for decrease nephrotoxic effects and >electrolyte abnormalities. Patients and Methods: The study was conducted as a randomized clinical trial. The sample consisted of 60 patients with gastric and lung cancer treated with cisplatin in Ahvaz Shafa hospital. Patients were randomly divided into 2 equal groups. Both groups were treated with cisplatin over a period of 6 to 18 weeks. The first group received 50 mg/m2/day of cisplatin during one day and the second group received 25 mg/m2/day in 2 days. Electrolytes in each period and renal function at baseline and 6 months after starting treatment was assessed. Results: Difference of mean of renal function and nephrotoxicity incidence in the 2 groups was statistically significant. The odds of hypokalemia in 1-day group was higher than 2-day group (odds ratio [OR] = 6.5), which was statistically significant. However there was no significant relationship between the types of treatment and the risk of hypocalcemia, hypomagnesemia and hyperuricemia. Conclusion: The result of this study showed that, the divided administration of cisplatin reduces the nephrotoxic and hypokalemia effects of this drug, however it had not significant influence on hypomagnesemia, hypocalcaemia, and hyperuricemia. PMID:26468480

  2. Hand hygiene regimens for the reduction of risk in food service environments.

    PubMed

    Edmonds, Sarah L; McCormack, Robert R; Zhou, Sifang Steve; Macinga, David R; Fricker, Christopher M

    2012-07-01

    Pathogenic strains of Escherichia coli and human norovirus are the main etiologic agents of foodborne illness resulting from inadequate hand hygiene practices by food service workers. This study was conducted to evaluate the antibacterial and antiviral efficacy of various hand hygiene product regimens under different soil conditions representative of those in food service settings and assess the impact of product formulation on this efficacy. On hands contaminated with chicken broth containing E. coli, representing a moderate soil load, a regimen combining an antimicrobial hand washing product with a 70% ethanol advanced formula (EtOH AF) gel achieved a 5.22-log reduction, whereas a nonantimicrobial hand washing product alone achieved a 3.10log reduction. When hands were heavily soiled from handling ground beef containing E. coli, a wash-sanitize regimen with a 0.5% chloroxylenol antimicrobial hand washing product and the 70% EtOH AF gel achieved a 4.60-log reduction, whereas a wash-sanitize regimen with a 62% EtOH foam achieved a 4.11-log reduction. Sanitizing with the 70% EtOH AF gel alone was more effective than hand washing with a nonantimicrobial product for reducing murine norovirus (MNV), a surrogate for human norovirus, with 2.60- and 1.79-log reductions, respectively. When combined with hand washing, the 70% EtOH AF gel produced a 3.19-log reduction against MNV. A regimen using the SaniTwice protocol with the 70% EtOH AF gel produced a 4.04-log reduction against MNV. These data suggest that although the process of hand washing helped to remove pathogens from the hands, use of a wash-sanitize regimen was even more effective for reducing organisms. Use of a high-efficacy sanitizer as part of a wash-sanitize regimen further increased the efficacy of the regimen. The use of a well-formulated alcohol-based hand rub as part of a wash-sanitize regimen should be considered as a means to reduce risk of infection transmission in food service facilities.

  3. Efficacy and toxicity of different concurrent chemoradiotherapy regimens in the treatment of advanced cervical cancer

    PubMed Central

    Fu, Zhan-Zhao; Li, Kun; Peng, Yong; Zheng, Yue; Cao, Li-Yan; Zhang, Yun-Jie; Sun, Yong-Mei

    2017-01-01

    Abstract Objective: The aim of this study was to compare the efficacy and toxicity of different concurrent chemoradiotherapy (CCRT) regimens in the treatment of advanced cervical cancer (CC) by adopting a network meta-analysis. Methods: We searched PubMed and Cochrane Library from the inception of these databases to September 2016, and all cohort studies (CSs) related to different CCRT regimens in the treatment of CC were included. A network analysis was adopted to compare the combination of direct and indirect evidence, to analyze the odds ratio (OR), and to draw a surface under the cumulative ranking curve of the efficacy and toxicity of different CCRT regimens for CC. Cluster analyses were used to group each category based on similar treatment regimens. Results: Nineteen CSs were enrolled in this network meta-analysis, including 12 CCRT regimens (radiotherapy [RT], CCRT [cisplatin], CCRT [vinorelbine], CCRT [paclitaxel], CCRT [hydroxyurea], CCRT [cisplatin + FU], CCRT [cisplatin + gemcitabine], CCRT [cisplatin + docetaxel], CCRT [cisplatin + paclitaxel], CCRT [cisplatin + amifostine], CCRT [cisplatin + FU + hydroxyurea], and CCRT [cisplatin + vincristine + bleomycin]). The results of the network meta-analysis showed that regarding efficacy, the overall response rate of CCRT (cisplatin + docetaxel) was higher than RT, and the 5-year overall survival (OS) rate of CCRT (cisplatin + FU + hydroxyurea) was relatively higher than CCRT (hydroxyurea). As for toxicity, CCRT (cisplatin) had a lower incidence of leukopenia than CCRT (hydroxyurea), CCRT (cisplatin + FU) and CCRT (cisplatin + paclitaxel), and the incidences of diarrhea and vomiting in CCRT (cisplatin) were lower than those in CCRT (cisplatin + gemcitabine). Additionally, the cluster analysis showed that CCRT (cisplatin) had relatively lower incidences of both hematotoxicity and gastrointestinal toxicity, and CCRT (paclitaxel) had lower

  4. Additional Drug Resistance Patterns among Multidrug-Resistant Tuberculosis Patients in Korea: Implications for Regimen Design

    PubMed Central

    2017-01-01

    Detailed information on additional drug resistance patterns of multidrug-resistant tuberculosis (MDR-TB) is essential to build an effective treatment regimen; however, such data are scarce in Korea. We retrospectively analyzed the results of phenotypic drug susceptibility testing (DST) of culture confirmed-TB patients from January 2010 to December 2014 in 7 university hospitals in Korea. MDR-TB was identified among 6.8% (n = 378) of 5,599 isolates. A total of 57.1% (n = 216) of the MDR-TB patients had never been treated for TB. Strains from MDR-TB patients showed additional resistance to pyrazinamide (PZA) (35.7%), any second-line injectable drug (19.3%), and any fluoroquinolone (26.2%). Extensively drug resistant TB comprised 12.4% (n = 47) of the MDR-TB patients. Of 378 MDR-TB patients, 50.3% (n = 190) were eligible for the shorter MDR-TB regimen, and 50.0% (n = 189) were fully susceptible to the 5 drugs comprising the standard conventional regimen (PZA, kanamycin, ofloxoacin, prothionamide, and cycloserine). In conclusion, the proportion of new patients and the levels of additional drug resistance were high in MDR-TB patients. Considering the high levels of drug resistance, the shorter MDR-TB treatment regimen may not be feasible; instead, an individually tailored regimen based on the results of molecular and phenotypic DST may be more appropriate in MDR-TB patients in Korea. PMID:28244290

  5. Potential Economic Viability of Two Proposed Rifapentine-Based Regimens for Treatment of Latent Tuberculosis Infection

    PubMed Central

    Holland, David P.; Sanders, Gillian D.; Hamilton, Carol D.; Stout, Jason E.

    2011-01-01

    Rationale Rifapentine-based regimens for treating latent tuberculosis infection (LTBI) are being considered for future clinical trials, but even if they prove effective, high drug costs may limit their economic viability. Objectives To inform clinical trial design by estimating the potential costs and effectiveness of rifapentine-based regimens for treatment of latent tuberculosis infection (LTBI). Methods We used a Markov model to estimate cost and societal benefits for three regimens for treating LTBI: Isoniazid/rifapentine daily for one month, isoniazid/rifapentine weekly for three months (self-administered and directly-observed), and isoniazid daily for nine months; a strategy of “no treatment” used for comparison. Costs, quality-adjusted life-years gained, and instances of active tuberculosis averted were calculated for all arms. Results Both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months were less expensive and more effective than other strategies under a wide variety of clinically plausibly parameter estimates. Daily isoniazid/rifapentine for one month was the least expensive and most effective regimen. Conclusions Daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months should be studied in a large-scale clinical trial for efficacy. Because both regimens performed well even if their efficacy is somewhat reduced, study designers should consider relaxing non-inferiority boundaries. PMID:21789248

  6. Potent Twice-Weekly Rifapentine-containing Regimens in Murine Tuberculosis

    PubMed Central

    Rosenthal, Ian M.; Williams, Kathy; Tyagi, Sandeep; Peloquin, Charles A.; Vernon, Andrew A.; Bishai, William R.; Grosset, Jacques H.; Nuermberger, Eric L.

    2006-01-01

    Rationale: Recent studies have demonstrated that intermittent administration of rifamycin-based regimens results in higher rates of tuberculosis relapse and treatment failure compared with daily therapy. Twice-weekly treatment with rifampin, isoniazid, and pyrazinamide may be improved by increasing Mycobacterium tuberculosis exposure to rifamycin by substituting rifapentine for rifampin. Methods: To test this hypothesis, we compared the activities of standard daily and twice-weekly rifampin plus isoniazid-based regimens to those of twice-weekly rifapentine plus isoniazid- or moxifloxacin-containing regimens in the murine model of tuberculosis. Relapse rates were assessed after 4, 5, and 6 mo of treatment to assess stable cure. Single- and multiple-dose pharmacokinetics of rifampin and rifapentine were also determined. Results: After 2 mo of treatment, twice-weekly therapy with rifapentine (15 or 20 mg/kg), moxifloxacin, and pyrazinamide was significantly more active than standard daily or twice-weekly therapy with rifampin, isoniazid, and pyrazinamide. Stable cure was achieved after 4 mo of twice-weekly rifapentine plus isoniazid- or moxifloxacin-containing therapy, but only after 6 mo of standard daily therapy. Twice-weekly rifapentine (15 mg/kg) displayed more favorable pharmacodynamics than did daily rifampin (10 mg/kg). Conclusions: By virtue of the enhanced rifamycin exposure, twice-weekly regimens containing rifapentine (15 or 20 mg/kg) may permit shortening the current treatment duration by 2 mo. Such regimens warrant clinical investigation. PMID:16574936

  7. Experimental endocrine manipulation by contraceptive regimen in the male marmoset (Callithrix jacchus).

    PubMed

    Wistuba, Joachim; Luetjens, C Marc; Ehmcke, Jens; Redmann, Klaus; Damm, Oliver S; Steinhoff, Antje; Sandhowe-Klaverkamp, Reinhild; Nieschlag, Eberhard; Simoni, Manuela; Schlatt, Stefan

    2013-04-01

    Marmosets are used as preclinical model in reproductive research. In contrast to other primates, they display short gestation times rendering this species valid for exploration of effects on fertility. However, their peculiar endocrine regulation differs from a those of macaques and humans. We subjected male marmosets to previously clinically tested hormonal regimens that are known to effectively suppress spermatogenesis. Beside a control group, seven groups (each n=6) were investigated for different periods of up to 42 months: regimen I, (four groups) received testosterone undecanoate (TU) and norethisterone enanthate (NETE); regimen II, (two groups) received TU and NETE followed by NETE only; and regimen III, (one group) received NETE only. Testicular volume, cell ploidy and histology, endocrine changes and fertility were monitored weekly. TU and NETE and initial TU and NETE treatment followed by NETE failed to suppress spermatogenesis and fertility. Testicular volumes dropped, although spermatogenesis was only mildly affected; however, testicular cellular composition remained stable. Serum testosterone dropped when NETE was given alone but the animals remained fertile. Compared with controls, no significant changes were observed in sperm motility and fertility. Administration of TU and NETE affected testicular function only mildly, indicating that the regulatory role of chorionic gonadotrophin and testosterone on spermatogenesis is obviously limited and testicular function is maintained, although the endocrine axis is affected by the treatment. In conclusion, marmosets showed a different response to regimens of male contraception from macaques or men and have to be considered as a problematic model for preclinical trials of male hormonal contraception.

  8. Randomized multicentric Italian study on two treatment regimens for marrow relapse in childhood acute lymphoblastic leukemia.

    PubMed

    Rossi, M R; Masera, G; Zurlo, M G; Amadori, S; Mandelli, F; Bagnulo, S; Carli, M; Zanesco, L; Dini, G; Guazzelli, C

    1986-01-01

    This paper reports the results of a multicentric randomized clinical trial on the treatment of first hematological relapse in childhood ALL. Induction treatment consisted of vincristine, adriamycin, L-asparaginase, and prednisone. Patients achieving complete remission were randomized to two maintenance regimens (A and B). Regimen A consisted of five different drug associations including VM26 and IDMTX in a sequential schedule; Regimen B was essentially classical Spiers schedule for the first year, followed by a milder treatment. Eighty-four of 102 evaluable patients (82%) achieved second complete remission. The two maintenance regimens were similar as regards duration of second complete remission (median duration A, 32 weeks; B, 37 weeks) and toxicity. Better results were obtained in patients relapsing after 12 months from suspension of treatment in first complete remission than in those relapsing within the first year off therapy (82.8% vs. 31.4%). In group A fewer CNS relapses were reported. The two regimens produced results similar to those reported by other authors. The good prognosis in patients relapsing at least 1 year after treatment suspension in first complete remission must be emphasized.

  9. Effect of different bleaching regimens on the flexural strength of hybrid composite resin

    PubMed Central

    Feiz, Atiyeh; Samanian, Noushmehr; Davoudi, Amin; Badrian, Hamid

    2016-01-01

    Background: The entire effects of different bleaching regimens on the mechanical properties of composite resins have remained unknown. The purpose of this study was to evaluate the effects of different bleaching regimens on the flexural strength (FS) of hybrid composite resins. Materials and Methods: In this in vitro study, 80 bar-shaped specimens of hybrid composite resins were fabricated and randomly divided into four groups, 20 specimens in each group. First group (C) was considered as control. The other groups were treated by home bleaching (HB) agent, in-office bleaching (IB) agent, and the combination regimens (HIB), respectively. The FS was evaluated by three-point bending test by using a Universal Testing Machine. All data were analyzed by using Statistical Package for the Social Sciences (SPSS) software version 18, analysis of variance (ANOVA), and Turkey's post hoc statistical tests (α = 0.05). Results: The maximum mean value of FS was seen in HB group with significant differences to other groups (P < 0.05). Also, the minimum FS was observed in group HIB. Conclusion: Application of different bleaching regimens does not have any adverse effect on the FS of hybrid composite resins. However, the administration of HB regimens seemed to have lesser negative impact on the FS. PMID:27099423

  10. Cleansing the colon in gallium-67 scintigraphy: a prospective comparison of regimens

    SciTech Connect

    Novetsky, G.J.; Turner, D.A.; Ali, A.; Raynor, W.J. Jr.; Fordham, E.W.

    1981-01-01

    Colonic accumulation of gallium-67 frequently complicates the interpretation of gallium-67 scintigrams. Although various modes of cleansing the colon prior to scintigraphy have been suggested, there is controversy over their efficacy and none have been tested prospectively. Three hundred nine patients undergoing gallium-67 scintigraphy were randomly assigned to one of four cleansing regimens: (1) a high fiber diet (78 patients); (2) castor oil (76); (3) milk of magnesia and cascara (76); and (4) not preparation (79). Patient compliance rates for the four regimens were 17%, 32%, 36%, and 46%, respectively. After noncompliant patients were excluded, gallium-67 scintigrams were graded for colonic activity on a scale of 0-3 by three independent, experienced observers. Gallium-67 activity in the colon was significantly less after administration of castor oil than after no preparation (p . 0.047). A high fiber diet also resulted in a substantial reduction of colonic activity when compared with no preparation; the difference, however, was not statistically significant (p . 0.083). Regimen 3 did not produce significantly better results than regimen 4 (p . 0.42). A major impediment to the success of any cleansing regimen seems to be poor compliance of patients.

  11. Cleansing the colon in gallium-67 scintigraphy: a prospective comparison of regimens

    SciTech Connect

    Novetsky, G.J.; Turner, D.A.; Ali, A.; Raynor, W.J.; Fordham, E.W.

    1981-11-01

    Colonic accumulation of gallium-67 frequently complicates the interpretation of gallium-67 scintigrams. Although various modes of cleansing the colon prior to scintigraphy have been suggested, there is controversy over their efficacy and none have been tested prospectively. Three hundred nine patients undergoing gallium-67 scintigraphy were randomly assigned to one of four cleansing regimens: (1) a high fiber diet (78 patients); (2) castor oil (76); (3) milk of magnesia and cascara (76); and (4) no preparation (79). Patient compliance rates for the four regimens were 17%, 32%, 36%, and 46%, respectively. After noncompliant patients were excluded, gallium-67 scintigrams were graded for colonic activity on a scale of 0-3 by three independent, experienced observers. Gallium-67 activity in the colon was significantly less after adminstration of castor oil than after no prepartion (p = 0.083). Regimen 3 did not produce significantly better results than regimen 4 (p = 0.42). A major impediment to the success of any cleansing regimen seems to be poor compliance of patients.

  12. In situ synthesis carbonated hydroxyapatite layers on enamel slices with acidic amino acids by a novel two-step method.

    PubMed

    Wu, Xiaoguang; Zhao, Xu; Li, Yi; Yang, Tao; Yan, Xiujuan; Wang, Ke

    2015-09-01

    In situ fabrication of carbonated hydroxyapatite (CHA) remineralization layer on an enamel slice was completed in a novel, biomimetic two-step method. First, a CaCO3 layer was synthesized on the surface of demineralized enamel using an acidic amino acid (aspartic acid or glutamate acid) as a soft template. Second, at the same concentration of the acidic amino acid, rod-like carbonated hydroxyapatite was produced with the CaCO3 layer as a sacrificial template and a reactant. The morphology, crystallinity and other physicochemical properties of the crystals were characterized using field emission scanning electron microscopy (FESEM), Fourier transform infrared spectrometry (FTIR), X-ray diffraction (XRD) and energy-dispersive X-ray analysis (EDAX), respectively. Acidic amino acid could promote the uniform deposition of hydroxyapatite with rod-like crystals via absorption of phosphate and carbonate ions from the reaction solution. Moreover, compared with hydroxyapatite crystals coated on the enamel when synthesized by a one-step method, the CaCO3 coating that was synthesized in the first step acted as an active bridge layer and sacrificial template. It played a vital role in orienting the artificial coating layer through the template effect. The results show that the rod-like carbonated hydroxyapatite crystals grow into bundles, which are similar in size and appearance to prisms in human enamel, when using the two-step method with either aspartic acid or acidic glutamate (20.00 mmol/L).

  13. A dual drug regimen synergistically blocks human parainfluenza virus infection

    NASA Astrophysics Data System (ADS)

    Bailly, Benjamin; Dirr, Larissa; El-Deeb, Ibrahim M.; Altmeyer, Ralf; Guillon, Patrice; von Itzstein, Mark

    2016-04-01

    Human parainfluenza type-3 virus (hPIV-3) is one of the principal aetiological agents of acute respiratory illness in infants worldwide and also shows high disease severity in the elderly and immunocompromised, but neither therapies nor vaccines are available to treat or prevent infection, respectively. Using a multidisciplinary approach we report herein that the approved drug suramin acts as a non-competitive in vitro inhibitor of the hPIV-3 haemagglutinin-neuraminidase (HN). Furthermore, the drug inhibits viral replication in mammalian epithelial cells with an IC50 of 30 μM, when applied post-adsorption. Significantly, we show in cell-based drug-combination studies using virus infection blockade assays, that suramin acts synergistically with the anti-influenza virus drug zanamivir. Our data suggests that lower concentrations of both drugs can be used to yield high levels of inhibition. Finally, using NMR spectroscopy and in silico docking simulations we confirmed that suramin binds HN simultaneously with zanamivir. This binding event occurs most likely in the vicinity of the protein primary binding site, resulting in an enhancement of the inhibitory potential of the N-acetylneuraminic acid-based inhibitor. This study offers a potentially exciting avenue for the treatment of parainfluenza infection by a combinatorial repurposing approach of well-established approved drugs.

  14. Low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor priming regimen versus idarubicin plus cytarabine regimen as induction therapy for older patients with acute myeloid leukemia.

    PubMed

    Jin, Jie; Chen, Jian; Suo, Shanshan; Qian, Wenbin; Meng, Haitao; Mai, Wenyuan; Tong, Hongyan; Huang, Jian; Yu, Wenjuan; Wei, Juyin; Lou, Yinjun

    2015-06-01

    With limited data available on the low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor (CAG) regimen in newly diagnosed older patients with acute myeloid leukemia (AML), this study aimed at comparing the efficacy and toxicity of CAG with idarubicin plus cytarabine (IA) remission induction therapy in these patients. A total of 154 consecutive patients (52 with CAG and 102 with IA) were retrospectively analyzed. The patients in the CAG group had a higher median age (68 vs. 65 years, p = 0.002) and a higher proportion of previous myelodysplastic syndrome (25.0% vs. 2.9%, p < 0.0001) compared to those in the IA group. The complete remission rates with the CAG and IA regimens were 55.8% and 52.9% (p = 0.864). The median overall survival (12.1 vs. 11.7 months, p = 0.650) and 3-year disease-free survival rates (29.6% vs. 48.6%, p = 0.657) were not statistically different in the two groups. The CAG regimen might be an alternative to conventional chemotherapy in older patients with AML.

  15. The pharmacokinetics of three multiple dose regimens of chloroquine: implications for malaria chemoprophylaxis.

    PubMed Central

    Wetsteyn, J C; De Vries, P J; Oosterhuis, B; Van Boxtel, C J

    1995-01-01

    The pharmacokinetics of chloroquine were studied in healthy volunteers who received one of three different multiple-dose regimens for 3 weeks: once weekly 300 mg, twice weekly 200 mg and once daily 50 mg chloroquine. Plasma concentrations of chloroquine and metabolites were determined by h.p.l.c. with fluorescence detection. The concentration-time course was fitted to a multiple-dose pharmacokinetic model. Volume of distribution, elimination half-life and clearance were not different for the three regimens, ranging from 250-302 l kg-1, 374-479 h and 0.44-0.58 l h-1 kg-1 respectively. After the first week of all dosage regimens, peak and trough concentrations of chloroquine were above 16 micrograms l-1, sufficiently suppressive for chloroquine-sensitive P. falciparum strains. These data suggest that once daily chloroquine could be combined with proguanil in a single tablet and should improve compliance when given for malaria chemoprophylaxis. PMID:7654492

  16. Efficacy and tolerability of 5-day azacytidine dose-intensified regimen in higher-risk MDS.

    PubMed

    Pierdomenico, Francesca; Esteves, Susana; Almeida, Antonio

    2013-09-01

    Higher-risk myelodysplastic syndromes (MDS) are aggressive disorders with rapid progression to AML and short survival. Azacitidine has shown unprecedented survival advantage in these patients but its treatment schedule involves daily hospital administrations for 7 days every 4 weeks. Due to patient and staffing constraints, we have treated 50 patients with a 5-day dose-intensified (500 mg/m(2) total monthly dose divided in 5 days) azacitidine schedule in our center. The regimen was well tolerated, with Grade 3/4 adverse events seen in 24 % patients and only two discontinuations due to toxicity. The response rate was similar to that reported with the 7-day schedule: 16 % complete remissions, 32 % partial remissions, and 62 % transfusion independence. The median survival was 19.2 months from diagnosis. In addition, this regimen reduced hospital visits by 28 % and drug use by 30 %. Our results demonstrate the safety and efficacy of a dose-intensified 5-day regimen.

  17. Partnerships to Design Novel Regimens to Treat Childhood Tuberculosis, Sui Generis: The Road Ahead

    PubMed Central

    Gumbo, Tawanda; Makhene, Mamodikoe K.; Seddon, James A.

    2016-01-01

    There has been a recent expansion of preclinical models to predict the efficacy of regimens to treat adults with tuberculosis. Despite increasing global interest in childhood tuberculosis, these same tools have not been employed to develop pediatric regimens. Children differ from adults in bacillary burden, spectrum of disease, the metabolism and distribution of antituberculosis drugs, and the toxicity experienced. The studies documented in this series describe a proof-of-concept approach to pediatric regimen development. We propose a program of investigation that would take this forward into a systematic and comprehensive method to find optimal drug combinations to use in children, ideal exposures, and required dosing. Although the number of possible drug combinations is extensive, a series of principles could be employed to select likely effective regimens. Regimens should avoid drugs with overlapping toxicity or linked mechanisms of resistance and should aim to include drugs with different mechanisms of action and ones that are able to target different subpopulations of mycobacteria. Finally drugs should penetrate into body sites necessary for treating pediatric disease. At an early stage, this body of work would need to engage with regulatory agencies and bodies that formulate guidelines, so that once regimens and dosages are identified, translation into clinical studies and clinical practice can be rapid. The development of child-friendly drug formulations would need to be carried out in parallel so that pharmacokinetic studies can be undertaken as formulations are created. Significant research and development would be required and a wide range of stakeholders would need to be engaged. The time is right to consider a more thoughtful and systematic approach toward identifying, testing, and comparing combinations of drugs for children with tuberculosis. PMID:27742642

  18. Clofazimine shortens the duration of the first-line treatment regimen for experimental chemotherapy of tuberculosis.

    PubMed

    Tyagi, Sandeep; Ammerman, Nicole C; Li, Si-Yang; Adamson, John; Converse, Paul J; Swanson, Rosemary V; Almeida, Deepak V; Grosset, Jacques H

    2015-01-20

    A key drug for the treatment of leprosy, clofazimine has recently been associated with highly effective and significantly shortened regimens for the treatment of multidrug-resistant tuberculosis (TB). Consequently, we hypothesized that clofazimine may also shorten the duration of treatment for drug-susceptible TB. We conducted a controlled trial in the mouse model of TB chemotherapy comparing the activity of the 6-mo standard regimen for TB treatment, i.e., 2 mo of daily rifampin, isoniazid, pyrazinamide, and ethambutol followed by 4 mo of rifampin and isoniazid, with a 4-mo clofazimine-containing regimen: 2 mo of daily rifampin, isoniazid, pyrazinamide, and clofazimine followed by 2 mo of rifampin, isoniazid, and clofazimine. Treatment efficacy was assessed on the basis of Mycobacterium tuberculosis colony counts in the lungs and spleens during treatment and on the proportion of mice with culture-positive relapse 6 mo after treatment cessation. No additive effect of clofazimine was observed after the first week of treatment, but, by the second week of treatment, the colony counts were significantly lower in the clofazimine-treated mice than in the mice receiving the standard regimen. Lung culture conversion was obtained after 3 and 5 mo in mice treated with the clofazimine-containing and standard regimens, respectively, and relapse-free cure was obtained after 3 and 6 mo of treatment with the clofazimine-containing and standard regimens, respectively. Thus, clofazimine is a promising anti-TB drug with the potential to shorten the duration of TB chemotherapy by at least half (3 mo vs. 6 mo) in the mouse model of TB.

  19. Sterilizing Activity of Second-Line Regimens Containing TMC207 in a Murine Model of Tuberculosis

    PubMed Central

    Lounis, Nacer; Andries, Koen; Jarlier, Vincent

    2011-01-01

    Rationale The sterilizing activity of the regimen used to treat multidrug resistant tuberculosis (MDR TB) has not been studied in a mouse model. Objective and Methods Swiss mice were intravenously inoculated with 6 log10 of Mycobacterium tuberculosis (TB) strain H37Rv, treated with second-line drug combinations with or without the diarylquinoline TMC207, and then followed without treatment for 3 more months to determine relapse rates (modified Cornell model). Measurements Bactericidal efficacy was assessed by quantitative lung colony-forming unit (CFU) counts. Sterilizing efficacy was assessed by measuring bacteriological relapse rates 3 months after the end of treatment. Main Results The relapse rate observed after 12 months treatment with the WHO recommended MDR TB regimen (amikacin, ethionamide, pyrazinamide and moxifloxacin) was equivalent to the relapse rate observed after 6 months treatment with the recommended drug susceptible TB regimen (rifampin, isoniazid and pyrazinamide). When TMC207 was added to this MDR TB regimen, the treatment duration needed to reach the same relapse rate dropped to 6 months. A similar relapse rate was also obtained with a 6-month completely oral regimen including TMC207, moxifloxacin and pyrazinamide but excluding both amikacin and ethionamide. Conclusions In this murine model the duration of the WHO MDR TB treatment could be reduced to 12 months instead of the recommended 18–24 months. The inclusion of TMC207 in the WHO MDR TB treatment regimen has the potential to further shorten the treatment duration and at the same time to simplify treatment by eliminating the need to include an injectable aminoglycoside. PMID:21408613

  20. Dietary roughage regimen for feedlot steers: reduced roughage level (2%) during the mid-finishing period.

    PubMed

    Bartle, S J; Preston, R L

    1991-09-01

    Because roughage in feedlot diets is one of the most expensive ingredients on an energy basis, regimens that minimize roughage usage are of interest. Crossbred steers of British breeds (n = 112, initial BW = 405 kg) were used to compare the feeding of diets containing 2% roughage from d 22 through 84 and 10% roughage from d 85 to finish (d 133; 2/10%) to the feeding of 10% roughage throughout the finishing period (10/10%); all diets were based on steam-flaked sorghum grain and contained monensin and tylosin. When the 2% roughage diet was fed, steers consumed less feed (6.8 vs 7.8 kg/d, P less than .01), tended to gain less (1.11 vs 1.20 kg/d, P = .13), and were numerically more efficient (16.5 vs 15.5 kg of gain/100 kg of DMI, P greater than .2) than steers fed the 10% roughage diet (10/10%). After the roughage content was increased from 2 to 10% on d 85 (all steers fed 10% roughage), steers fed the 2/10% regimen had greater DMI (8.4 vs 8.0 kg/d, P = .08) and ADG (1.29 vs 1.09 kg, P = .06), and tended to be more efficient (15.4 vs 13.6 kg of gain/100 kg of DMI, P = .10) than steers fed the 10/10% regimen. Steers fed the two regimens had similar (P greater than .2) overall gain performance. The 2/10% regimen tended to have a greater percentage of Choice carcasses (58 vs 42%, P = .14) and numerically more liver abscesses (24 vs 15%, P greater than .2) than the 10/10% regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Kidney Injury Associated with Telavancin Dosing Regimen in an Animal Model

    PubMed Central

    Ledesma, Kimberly R.; Bowers, Dana R.; Zhou, Jian; Truong, Luan D.

    2015-01-01

    The elevation of serum creatinine levels is a concern with telavancin therapy. We examined the onset of kidney injury associated with telavancin in an animal model. Urine samples were collected at baseline and daily to determine the concentrations of kidney injury molecule 1 (KIM-1), a marker for early kidney injury. When a clinically relevant exposure of telavancin was given daily to rats, some differences in kidney injury were attributed to the dosing regimen. Further investigations of alternative telavancin dosing regimens are warranted. PMID:25712358

  2. Remission induction and remission maintenance in adult acute nonlymphocytic leukemia employing a modified cytostatic (COAP) regimen.

    PubMed

    Gerecke, D; Hirschmann, W D; Voigtmann, R; Gross, R

    1979-07-01

    Thirty adult patients suffering from acute nonlymphocytic leukemia (ANLL) were treated according to a modified COAP regimen. Vincristine, cyclophosphamide, and prednisone were given by push injection, while cytosine arabinoside was infused over periods of 8 h. Nineteen patients (63%) achieved complete remission. Remission maintenance therapy consisted of 6-mercaptopurine daily and methotrexate twice weekly. Later in the study, COAP consolidation and reinduction was added, which improved the median duration of complete remission from 7 to 24 months. Comparison of the results with the literature shows that the modified COAP regimen is one of the most effective treatment schedules for adult ANLL.

  3. Efavirenz versus boosted atazanavir-containing regimens and immunologic, virologic, and clinical outcomes

    PubMed Central

    Cain, Lauren E.; Caniglia, Ellen C.; Phillips, Andrew; Olson, Ashley; Muga, Roberto; Pérez-Hoyos, Santiago; Abgrall, Sophie; Costagliola, Dominique; Rubio, Rafael; Jarrín, Inma; Bucher, Heiner; Fehr, Jan; van Sighem, Ard; Reiss, Peter; Dabis, François; Vandenhende, Marie-Anne; Logan, Roger; Robins, James; Sterne, Jonathan A. C.; Justice, Amy; Tate, Janet; Touloumi, Giota; Paparizos, Vasilis; Esteve, Anna; Casabona, Jordi; Seng, Rémonie; Meyer, Laurence; Jose, Sophie; Sabin, Caroline; Hernán, Miguel A.

    2016-01-01

    Abstract Objective: To compare regimens consisting of either ritonavir-boosted atazanavir or efavirenz and a nucleoside reverse transcriptase inhibitor (NRTI) backbone with respect to clinical, immunologic, and virologic outcomes. Design: Prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States included in the HIV-CAUSAL Collaboration. Methods: HIV-positive, antiretroviral therapy-naive, and acquired immune deficiency syndrome (AIDS)-free individuals were followed from the time they started an atazanavir or efavirenz regimen. We estimated an analog of the “intention-to-treat” effect for efavirenz versus atazanavir regimens on clinical, immunologic, and virologic outcomes with adjustment via inverse probability weighting for time-varying covariates. Results: A total of 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths) and 18,786 individuals started an efavirenz regimen (389 deaths, 825 AIDS-defining illnesses or deaths). During a median follow-up of 31 months, the hazard ratios (95% confidence intervals) were 0.98 (0.77, 1.24) for death and 1.09 (0.91, 1.30) for AIDS-defining illness or death comparing efavirenz with atazanavir regimens. The 5-year survival difference was 0.1% (95% confidence interval: −0.7%, 0.8%) and the AIDS-free survival difference was −0.3% (−1.2%, 0.6%). After 12 months, the mean change in CD4 cell count was 20.8 (95% confidence interval: 13.9, 27.8) cells/mm3 lower and the risk of virologic failure was 20% (14%, 26%) lower in the efavirenz regimens. Conclusion: Our estimates are consistent with a smaller 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with atazanavir regimens. No overall differences could be detected with respect to 5-year survival or AIDS-free survival. PMID:27741139

  4. Effect of two different long-sprint training regimens on sprint performance and associated metabolic responses.

    PubMed

    Hanon, Christine; Bernard, Olivier; Rabate, Mathieu; Claire, Thomas

    2012-06-01

    The purpose of this study was to analyze 2 different long-sprint training programs (TPs) of equal total work load, completed either with short recovery (SR) or long recovery (LR) between sets and to compare the effects of 6 long-sprint training sessions (TSs) conducted over a 2-week period on a 300-m performance. Fourteen trained subjects performed 3 pretraining maximal sprints (50-, 100-, and 300-m), were paired according to their 300-m performance, and randomly allocated to an LR or SR group, which performed 6 TSs consisting of sets of 150, 200, or 250 m. The recovery in the LR group was double that of the SR group. During the third TS and the 300-m pretest and posttest, blood pH, bicarbonate concentration ([HCO₃⁻]), excess-base (EB), and lactate concentration were recorded. Compared with a similar TS performed with SR, the LR training tends to induce a greater alteration of the acid-base balance: pH: 7.09 ± 0.08 (LR) and 7.14 ± 0.05 (SR) (p = 0.10), [HCO₃⁻]: 7.8 ± 1.9 (LR) and 9.6 ± 2.7 (SR) (p = 0.04), and EB: -21.1 ± 3.8 (LR) and -17.7 ± 2.8 (SR) (p = 0.11). A significant improvement in the 300-m performance between pre-TP and post-TP (42.45 ± 2.64 vs. 41.52 ± 2.45, p = 0.01) and significant decreases in pH (p < 0.01), EB (p < 0.001) and increase in [La] (p < 0.001) have been observed post-TP compared with those pre-TP. Although sprint training with longer recovery induces higher metabolic disturbances, both sprint training regimens allow a similar 300-m performance improvement with no concomitant significant progress in the 50- and 100-m performance.

  5. Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen

    SciTech Connect

    Sharabi, Y.; Sachs, D.H.

    1989-02-01

    The use of allogeneic bone marrow transplantation as a means of inducing donor-specific tolerance across MHC barriers could provide an immunologically specific conditioning regimen for organ transplantation. However, a major limitation to this approach is the toxicity of whole body irradiation as currently used to abrogate host resistance and permit marrow engraftment. The present study describes methodology for abrogating host resistance and permitting marrow engraftment without lethal irradiation. Our preparative protocol involves administration of anti-CD4 and anti-CD8 mAbs in vivo, 300-rad WBI, 700-rad thymic irradiation, and unmanipulated fully MHC-disparate bone marrow. B10 mice prepared by this regimen developed stable mixed lymphohematopoetic chimerism without any clinical evidence of graft-vs.-host disease. Engraftment was accompanied by induction of specific tolerance to donor skin grafts (B10.D2), while third-party skin grafts (B10.BR) were promptly rejected. Mice treated with the complete regimen without bone marrow transplantation appeared healthy and enjoyed long-term survival. This study therefore demonstrates that stable mixed chimerism with donor-specific tolerance can be induced across an MHC barrier after a nonlethal preparative regimen, without clinical GVHD and without the risk of aplasia.

  6. Autotransplant conditioning regimens for aggressive lymphoma: are we on the right road?

    PubMed

    Fernandez, H F; Escalón, M P; Pereira, D; Lazarus, H M

    2007-09-01

    High-dose chemotherapy and autologous stem cell transplant (ASCT) is the standard approach for chemosensitive, relapsed aggressive non-Hodgkin's lymphoma (NHL). Various conditioning regimens have been used as treatment before ASCT and disease-free (DFS) and overall survival (OS) rates range from 34 to 60% and 26 to 46%, respectively. To date, few comparative randomized trials have been performed and no regimen has demonstrated superiority to another. Reduction of disease relapse remains the major hurdle for improving patient outcome and in vitro and in vivo purging of lymphoma cells has not necessarily enhanced results. Rituximab pre-mobilization and post-transplant appear to provide better response rates with OS approaching 87-91% at 2-3 years. Newer approaches with radioimmunotherapy may raise DFS to 78% and OS to 93%, albeit with short follow-up. Advances in the conditioning regimens and supportive care have reduced transplant-related mortality to less than 10%. In this review we discuss commonly utilized conditioning regimens, describe their pros and cons and address purging and present conditioning strategies. Owing to the poor outcome with conventional chemotherapy in mantle cell, Burkitt's and T-cell lymphoma, we propose the standard approach of front-line ASCT for these high-risk lymphoma patients. Finally, we will present novel strategies, which can enhance the anti-lymphoma effect, at the same time reducing toxicity, to improve the outcome of ASCT in NHL patients.

  7. Evidence-Based Nursing of the 3C Therapeutic Regimen for Type 1 Diabetes.

    PubMed

    Wu, Jianya; Zou, Ling

    2015-05-01

    The aim of this study is to explore the efficacy of the 3C therapeutic regimen for type 1 diabetes. Thirty-nine patients with type 1 diabetes, who were hospitalized from January 2013 to April 2014, were included to receive 3C therapeutic regimen. Evidence-based nursing was performed in the treatment period and the efficacy was observed 6 days after therapy. Six days after the administration of the 3C therapeutic regimen, the fasting glucose levels in all 39 patients were controlled to be 4.4-6.0 mmol/L and 2h-postprandial glucose levels to be 4.4-7.8 mmol/L. Three patients had a glucose level <3.9 mmol/L, which was corrected after adjusting the dose of insulin infusion. Evidence-based nursing was provided in the treatment period and no nursing-associated complication occurred. All patients were satisfied with the nursing service. The efficacy of the 3C therapeutic regimen for type 1 diabetes is satisfactory. The evidence-based nursing can help to ensure the efficacy and improve the quality of nursing service.

  8. Adverse Reactions to Daily and Intermittent Rifampicin Regimens for Pulmonary Tuberculosis in Hong Kong*

    PubMed Central

    Aquinas, Sister Mary; Allan, W. G. L.; Horsfall, P. A. L.; Jenkins, P. K.; Hung-Yan, Wong; Girling, David; Tall, Ruth; Fox, Wallace

    1972-01-01

    This paper reports the nature, incidence, and severity of adverse reactions to regimens of rifampicin and ethambutol given once weekly, twice weekly, or daily and to a standard reserve regimen in a total of 330 Chinese failure patients who completed at least six months' chemotherapy in a therapeutic comparison in Hong Kong. The adverse reactions which occurred on the regimens of intermittent rifampicin were termed cutaneous, abdominal, “flu”, and respiratory; in addition, purpura and abnormal liver function tests were encountered. There was an association of adverse reactions with the interval between doses and with the dose size of rifampicin, the highest incidence occurring with once-weekly rifampicin in high dosage. A procedure was developed for managing adverse reactions to intermittent rifampicin. Of 202 patients treated with intermittent rifampicin 60 developed adverse reactions, but in only 7 (3%) was it necessary to terminate the drug, though a further 10 (5%) were changed to daily rifampicin. On daily rifampicin, generalized hypersensitivity, cutaneous reactions, (one with purpura), and impaired liver function were encountered. Adverse reactions on the standard ethionamide, pyrazinamide, and cycloserine regimen were frequent and some were serious. PMID:4259217

  9. The effects of a discretionary food allowance during a caloric restriction regimen with provided food

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of self-selected discretionary foods in a structured energy restricted diet on adherence to a caloric restriction (CR) regimen, dietary satisfaction, and weight loss were studied in 32 healthy, overweight (BMI 25-30 kg/m2) adults, aged 20-42y participating in the CALERIE trial. Subjects ...

  10. Intestinal Microbiota of Broiler Chickens As Affected by Litter Management Regimens.

    PubMed

    Wang, Lingling; Lilburn, Mike; Yu, Zhongtang

    2016-01-01

    Poultry litter is a mixture of bedding materials and enteric bacteria excreted by chickens, and it is typically reused for multiple growth cycles in commercial broiler production. Thus, bacteria can be transmitted from one growth cycle to the next via litter. However, it remains poorly understood how litter reuse affects development and composition of chicken gut microbiota. In this study, the effect of litter reuse on the microbiota in litter and in chicken gut was investigated using 2 litter management regimens: fresh vs. reused litter. Samples of ileal mucosa and cecal digesta were collected from young chicks (10 days of age) and mature birds (35 days of age). Based on analysis using DGGE and pyrosequencing of bacterial 16S rRNA gene amplicons, the microbiota of both the ileal mucosa and the cecal contents was affected by both litter management regimen and age of birds. Faecalibacterium, Oscillospira, Butyricicoccus, and one unclassified candidate genus closely related to Ruminococcus were most predominant in the cecal samples, while Lactobacillus was predominant in the ileal samples at both ages and in the cecal samples collected at day 10. At days 10 and 35, 8 and 3 genera, respectively, in the cecal luminal microbiota differed significantly in relative abundance between the 2 litter management regimens. Compared to the fresh litter, reused litter increased predominance of halotolerant/alkaliphilic bacteria and Faecalibacterium prausnitzii, a butyrate-producing gut bacterium. This study suggests that litter management regimens affect the chicken GI microbiota, which may impact the host nutritional status and intestinal health.

  11. Effect of feeding regimens on circadian rhythms: Implications for aging and longevity

    PubMed Central

    Froy, Oren; Miskin, Ruth

    2010-01-01

    Increased longevity and improved health can be achieved in mammals by two feeding regimens, caloric restriction (CR), which limits the amount of daily calorie intake, and intermittent fasting (IF), which allows the food to be availablead libitum every other day. The precise mechanisms mediating these beneficial effects are still unresolved. Resetting the circadian clock is another intervention that can lead to increased life span and well being, while clock disruption is associated with aging and morbidity. Currently, a large body of evidence links circadian rhythms with metabolism and feeding regimens. In particular, CR, and possibly also IF, can entrain the master clock located in the suprachiasmatic nuclei (SCN) of the brain hypothalamus. These findings raise the hypothesis that the beneficial effects exerted by these feeding regimens could be mediated, at least in part, through resetting of the circadian clock, thus leading to synchrony in metabolism and physiology. This hypothesis is reinforced by a transgenic mouse model showing spontaneously reduced eating alongside robust circadian rhythms and increased life span. This review will summarize recent findings concerning the relationships between feeding regimens, circadian rhythms, and metabolism with implications for ageing attenuation and life span extension. PMID:20228939

  12. [Treatment of malignant pheochromocytoma by combination of CVD regimen and transarterial embolization].

    PubMed

    Takeda, M; Katagiri, A; Kanai, T; Komeyama, T; Tsutsui, T; Katayama, Y; Kawakami, Y; Sato, S; Kimura, M; Odano, I

    1991-05-01

    We performed combination therapy with cyclophosphamide, Vincristine and Dacarbazine (CVD) regimen and transarterial embolization (TAE) in 2 cases of malignant pheochromocytoma with metastases. Case 1: 59-year-old female. After primary left adrenal lesion had been removed, recurrence at the left renal hilar region and metastases to the right iliac bone and 5th cervical vertebra occurred. We took 3 courses of CVD regimen after TAE for the lesions in the right iliac bone. Her endocrinological data has been normal for more than 1 year after treatment. Case 2: 29-year-old male. Total cystectomy, ileal conduit and pelvic lymphadenectomy had been performed for the primary lesion of the urinary bladder. 2 years after the 1st operation, metastases to the right obturator nodes and multiple bones occurred. We gave 3 courses of CVD regimen followed by TAE for the lesions in the right obturator nodes. Just after treatment, we could stop insulin and reduce anti-hypertension drugs, but the effect of treatment was temporary. In conclusion, combination of CVD regimen and TAE is effective for malignant pheochromocytoma with metastases.

  13. Caregiver Resources and Facilitation of Elderly Care Recipient Adherence to Health Regimens

    ERIC Educational Resources Information Center

    Greenberger, Haya; Litwin, Howard

    2003-01-01

    We studied the relationship between caregivers' personal and social resources and facilitation of adherence by elderly care recipients to a prescribed health regimen. Adherence facilitation was measured among 240 caregivers on a 45-item instrument constructed for this research. The facilitation score was regressed on caregivers' role-specific…

  14. Comparative effects of constant versus fluctuating thermal regimens on yellow perch growth, feed conversion and survival

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of fluctuating or constant thermal regimens on growth, mortality, and feed conversion were determined for juvenile yellow perch (Perca flavescens). Yellow perch averaging 156mm total length and 43g body weight were held in replicate 288L circular tanks for 129 days under: 1) a diel therm...

  15. Temozolomide chemoresistance heterogeneity in melanoma with different treatment regimens: DNA damage accumulation contribution.

    PubMed

    Boeckmann, Lars; Nickel, Ann-Christin; Kuschal, Christiane; Schaefer, Annika; Thoms, Kai-Martin; Schön, Michael P; Thomale, Jürgen; Emmert, Steffen

    2011-06-01

    The efficacy of temozolomide in melanoma treatment is low (response rate <20%) and may depend on the activity of O-methylguanine DNA methyltransferase (MGMT) and mismatch repair. We identified melanoma cell lines with different sensitivities to single versus prolonged clinical dosing regimens of temozolomide treatment and assessed a variety of potential resistance mechanisms using this model. We measured mRNA expression and promoter methylation of MGMT and essential mismatch repair genes (MLH1, MSH2). Cell cycle distribution, apoptosis/necrosis induction, O-methylguanine-adduct formation, and ABCB1 gene expression were assessed. We found that three cell lines, MelA, MelB, and MelC, were more sensitive to a single dose regimen than to a prolonged regimen, which would be expected to exhibit higher cytotoxicity. KAII and LIBR cell sensitivity was higher with regard to the prolonged treatment regimen, as expected. Only MelC expressed MGMT. Gene expression correlated well with promoter methylation. Temozolomide exposure did not alter mRNA expression. Different sensitivities to temozolomide were caused neither by delayed apoptosis induction due to early cell cycle arrest nor by O-methylguanine-adduct formation or efflux transporter expression. MelC was the most resistant cell line with rapid elimination of O-methylguanine adducts. This was in good agreement with its MGMT expression. The sensitive cell lines KAII and LIBR accumulated O-methylguanine adducts after a second treatment cycle with temozolomide in contrast with the other three cell lines. We conclude that MGMT expression and DNA adduct accumulation are relevant factors in temozolomide chemosensitivity. Considering individualized temozolomide treatment regimens either by quantification of DNA adducts or by chemosensitivity testing seems worthwhile clinically.

  16. Efficient intermittent rifapentine-moxifloxacin-containing short-course regimen for treatment of tuberculosis in mice.

    PubMed

    Veziris, N; Lounis, N; Chauffour, A; Truffot-Pernot, C; Jarlier, V

    2005-10-01

    Long-half-life drugs raise the hope of once-a-week administration of antituberculous treatment. In a previous study with the murine model of tuberculosis, the most active intermittent regimen which contained rifapentine (RFP), isoniazid (INH), and moxifloxacin (MXF) given once a week during 5.5 months, preceded by 2 weeks of daily treatment with INH, rifampin (RIF), pyrazinamide (PZA), and MXF, was less active than the standard 6-month daily RIF-INH-PZA regimen. We evaluated with the same model similar regimens in which we increased the dosing of rifapentine from 10 to 15 mg/kg of body weight and of moxifloxacin from 100 to 400 mg/kg. Mice infected intravenously by 6.2 x10(6) CFU of Mycobacterium tuberculosis H37Rv were treated 2 weeks later when infection was established. After 6 months of treatment, all mice had negative lung culture. After 3 months of follow-up, no relapse occurred in the two groups that received moxifloxacin at 400 mg/kg, whatever the dosage of RFP, and in the group receiving the standard RIF-INH-PZA control regimen. In contrast, in the two groups receiving moxifloxacin at a lower dosage, the relapse rate was significantly higher (13% in mice receiving RFP at 15 mg/kg and 27% in those receiving RFP at 10 mg/kg). Finally, the fully intermittent once-a-week regimen (26 drug ingestions) of INH, RFP (15 mg/kg), and MXF (400 mg/kg) led to a relapse rate of 11%. In conclusion, when used at high dosage, rifapentine and moxifloxacin are very efficient when combined with isoniazid in a once-a-week treatment in mouse tuberculosis.

  17. Efficient Intermittent Rifapentine-Moxifloxacin-Containing Short-Course Regimen for Treatment of Tuberculosis in Mice

    PubMed Central

    Veziris, N.; Lounis, N.; Chauffour, A.; Truffot-Pernot, C.; Jarlier, V.

    2005-01-01

    Long-half-life drugs raise the hope of once-a-week administration of antituberculous treatment. In a previous study with the murine model of tuberculosis, the most active intermittent regimen which contained rifapentine (RFP), isoniazid (INH), and moxifloxacin (MXF) given once a week during 5.5 months, preceded by 2 weeks of daily treatment with INH, rifampin (RIF), pyrazinamide (PZA), and MXF, was less active than the standard 6-month daily RIF-INH-PZA regimen. We evaluated with the same model similar regimens in which we increased the dosing of rifapentine from 10 to 15 mg/kg of body weight and of moxifloxacin from 100 to 400 mg/kg. Mice infected intravenously by 6.2 ×106 CFU of Mycobacterium tuberculosis H37Rv were treated 2 weeks later when infection was established. After 6 months of treatment, all mice had negative lung culture. After 3 months of follow-up, no relapse occurred in the two groups that received moxifloxacin at 400 mg/kg, whatever the dosage of RFP, and in the group receiving the standard RIF-INH-PZA control regimen. In contrast, in the two groups receiving moxifloxacin at a lower dosage, the relapse rate was significantly higher (13% in mice receiving RFP at 15 mg/kg and 27% in those receiving RFP at 10 mg/kg). Finally, the fully intermittent once-a-week regimen (26 drug ingestions) of INH, RFP (15 mg/kg), and MXF (400 mg/kg) led to a relapse rate of 11%. In conclusion, when used at high dosage, rifapentine and moxifloxacin are very efficient when combined with isoniazid in a once-a-week treatment in mouse tuberculosis. PMID:16189074

  18. Assessing the effectiveness of antiretroviral regimens in cohort studies involving HIV-positive injection drug users

    PubMed Central

    Lima, Viviane Dias; Nosyk, Bohdan; Wood, Evan; Kozai, Tsubasa; Zhang, Wendy; Chan, Keith; Montaner, Julio S.G.

    2015-01-01

    Objective We compared the effectiveness of different highly active antiretroviral therapy (HAART) regimens considering, separately, history of injection drug use (IDU) (yes/no). Design, methods A total of 1163 HIV-infected patients initiated HAART between 1 January 2000 and 28 February 2009 in British Columbia, Canada, and were followed until 28 February 2010. HAART effectiveness was measured by the ability to achieve viral suppression below 50 copies/ml at 6 months. We compared HAART regimens containing efavirenz and boosted atazanavir. We developed logistic regression models using different techniques to control for potential confounders. Results Among the 1163 patients, 796 (68%) achieved viral suppression at 6 months (32% reporting a history of IDU). Different confounding models yielded very similar odds ratios for achieving viral suppression. Boosted atazanavir-based HAART demonstrated to be the most effective regimen, showing a surprisingly higher benefit for patients with a history of IDU (odds ratios from different models ranged from 1.74–1.95 to 1.45–1.51). Conclusions The literature has conflicting results regarding the effectiveness of HAART to treat HIV infection among those with a history of IDU. We have shown that most patients, with and without a history of IDU, were able to achieve viral suppression at 6 months. Boosted atazanavir-based HAART was the most resilient regimen and it was more effective than efavirenz-based HAART among IDUs. Given the limited inclusion of IDU in clinical trials of HAART’s efficacy, a randomized clinical trial comparing different first-line HAART regimens among IDU is warranted based on these results. PMID:22555161

  19. [Aristolochic acid nephropathy].

    PubMed

    Witkowicz, Joanna

    2009-01-01

    Aristolochic acid nephropathy is a chronic, fibrosing, interstitial nephritis caused by aristolochic acid (AA), which is a component of the plants of Aristolochiacae family. It was first reported in 1993, in Belgium as a Chinese herb nephropathy, in patients who received a slimming regimen containing AA. The term aristolochic acid nephropathy also includes Balcan endemic nephropathy and other endemic tubulointerstitial fibrosis. Moreover, AA is a human carcinogen which induces urothelial cancer. The AA-containing herbs are banned in many countries and FDA published the warnings concerning the safety of AA-containing botanical remedies in 2000. Regarding the increasing interest in herbal medicines, uncontrolled access to botanical remedies and replacement of one herb by another AA-containing compounds makes thousands of people all around the world at risk of this grave disease.

  20. Adherence to Medical Regimens: Understanding the Effects of Cognitive Appraisal, Quality of Life, and Perceived Family Resiliency

    ERIC Educational Resources Information Center

    Frain, Michael P.; Bishop, Malachy; Tschopp, Molly K.; Ferrin, Micheal J.; Frain, Judy

    2009-01-01

    Adherence studies have taken center stage due to the life-threatening risks associated with nonadherence to highly active antiretroviral therapy (HAART) regimens for people with HIV/AIDS. This study examines adherence through self-report of individuals on HAART regimens in a manner to account for demand characteristic bias, while still attempting…

  1. A Combination Regimen Design Program Based on Pharmacodynamic Target Setting for Childhood Tuberculosis: Design Rules for the Playground

    PubMed Central

    Srivastava, Shashikant; Deshpande, Devyani; Pasipanodya, Jotam G.; Thomas, Tania; Swaminathan, Soumya; Nuermberger, Eric; Gumbo, Tawanda

    2016-01-01

    Children with tuberculosis are treated with drug regimens copied from adults despite significant differences in antibiotic pharmacokinetics, pathology, and the microbial burden between childhood and adult tuberculosis. We sought to develop a new and effective oral treatment regimen specific to children of different ages. We investigated and validated the concept that target drug concentrations associated with therapy failure and death in children are different from those of adults. On that basis, we proposed a 4-step program to rapidly develop treatment regimens for children. First, target drug concentrations for optimal efficacy are derived from preclinical models of disseminated tuberculosis that recapitulate pediatric pharmacokinetics, starting with monotherapy. Second, 2-drug combinations were examined for zones of synergy, antagonism, and additivity based on a whole exposure–response surface. Exposures associated with additivity or synergy were then combined and the regimen was compared to standard therapy. Third, several exposures of the third drug were added, and a 3-drug regimen was identified based on kill slopes in comparison to standard therapy. Fourth, computer-aided clinical trial simulations are used to identify clinical doses that achieve these kill rates in children in different age groups. The proposed program led to the development of a 3-drug combination regimen for children from scratch, independent of adult regimens, in <2 years. The regimens and doses can be tested in animal models and in clinical trials. PMID:27742637

  2. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection.

    PubMed

    2011-12-09

    Preventing tuberculosis (TB) by treating latent Mycobacterium tuberculosis infection (LTBI) is a cornerstone of the U.S. strategy for TB elimination. Three randomized controlled trials have shown that a new combination regimen of isoniazid (INH) and rifapentine (RPT) administered weekly for 12 weeks as directly observed therapy (DOT) is as effective for preventing TB as other regimens and is more likely to be completed than the U.S. standard regimen of 9 months of INH daily without DOT. This report provides CDC recommendations for using the INH-RPT regimen. The new regimen is recommended as an equal alternative to the 9-month INH regimen for otherwise healthy patients aged≥12 years who have LTBI and factors that are predictive of TB developing (e.g., recent exposure to contagious TB). The new regimen also can be considered for other categories of patients when it offers practical advantages. Although the INH-RPT regimen was well tolerated in treatment trials, monitoring for adverse effects is recommended. Severe adverse effects should be reported to the Food and Drug Administration (FDA) and CDC.

  3. The Role of Health Beliefs in the Regimen Adherence and Metabolic Control of Adolescents and Adults with Diabetes Mellitus.

    ERIC Educational Resources Information Center

    Brownlee-Duffeck, Martha; And Others

    1987-01-01

    Examined the role of health beliefs in diabetic regimen adherence and metabolic control. Health beliefs accounted for a statistically significant portion of the variance in both. For older patients perceived benefits of adhering to the diabetic regimen was most significant. For younger patients costs figured prominently in adherence and perceived…

  4. A Review of Myeloablative vs Reduced Intensity/Non-Myeloablative Regimens in Allogeneic Hematopoietic Stem Cell Transplantations

    PubMed Central

    Atilla, Erden; Ataca Atilla, Pınar; Demirer, Taner

    2017-01-01

    Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment option for both malignant and some benign hematological diseases. During the last decade, many of the newer high-dose regimens in different intensity have been developed specifically for patients with hematologic malignancies and solid tumors. Today there are three main approaches used prior to allogeneic transplantation: Myeloablative (MA), Reduced Intensity Conditioning (RIC) and Non-MA (NMA) regimens. MA regimens cause irreversible cytopenia and there is a requirement for stem cell support. Patients who receive NMA regimen have minimal cytopenia and this type of regimen can be given without stem cell support. RIC regimens do not fit the criteria of MA and NMA: the cytopenia is reversible and the stem cell support is necessary. NMA/RIC for Allo-HSCT has opened a new era for treating elderly patients and those with comorbidities. The RIC conditioning was used for 40% of all Allo-HSCT and this trend continue to increase. In this paper, we will review these regimens in the setting of especially allogeneic HSCT and our aim is to describe the history, features and impact of these conditioning regimens on specific diseases. PMID:28251017

  5. The Tolerability and Efficacy of a Three-product Anti-aging Treatment Regimen in Subjects with Moderate-to-severe Photodamage

    PubMed Central

    Lewis, Joseph; McHugh, Laura; Pellegrino, Arthur; Popescu, Lavinia

    2015-01-01

    Retinoids and alpha hydroxy acids differ in mechanism of action for treatment of photodamage, but concurrent use may produce a synergistic effect by combining retinoid-induced normalization of cellular differentiation with alpha hydroxy acid-induced exfoliation (in hydrophilic areas) and enhanced dermal and epidermal hydration. A recent bioengineered molecule, ethyl lactyl retinoate (alpha hydroxy acid retinoid conjugate), is the first to deliver alpha hydroxy acids and retinoids together in a hydrolysis-based time-released fashion. This could improve efficacy while minimizing irritation commonly associated with retinoid use. An eight-week clinical study was conducted to examine the efficacy and tolerability of this formulation; 25 women aged 54.1 ±8.9 years (mean ± SD) with moderate-to-severe photodamage (as determined by physician investigators using the Glogau Wrinkle Scale) employed a twice-daily regimen of cleanser (7.8% 1-lactic acid, 2% salicylic acid) and anti-aging serum (0.1% alpha hydroxy acids-retinoids, 6.5% 1-lactic acid) with concurrent use of sun protection factor 50+ sunscreen as needed. Longitudinal analysis of study data revealed statistically significant improvement in photodamage, dryness/flaking, dyschromia, and global appearance at eight weeks. All study products were well-tolerated throughout. Investigators concluded that the alpha hydroxy acid retinoid conjugate is a safe and effective topical therapy for moderate-to-severe photodamage, warranting further study, (clinicaltrials.gov, NCT02422836, https://clinicaltrials.gov/ct2/show/NCT02422836?term=NCT02422836) PMID:26557215

  6. Ifosfamide/etoposide alternating with high-dose methotrexate: evaluation of a chemotherapy regimen for poor-risk osteosarcoma

    PubMed Central

    Michelagnoli, M P; Lewis, I J; Gattamaneni, H R; Bailey, C C; Lashford, L S

    1999-01-01

    Fifteen patients with relapsed osteosarcoma were treated with an intensive combination chemotherapy schedule. Ifosfamide 2.5 g m−2 daily and etoposide 150 mg m−2 daily coincidentally for 3 days and high-dose methotrexate 8 g m−2 (with folinic acid rescue) on days 10–14 in a planned 21-day cycle. Feasibility, toxicity and response to this alternative combination for the treatment of relapsed osteosarcoma was assessed. There were 98 evaluable cycles for toxicity and tolerability. The majority of cycles were well tolerated. Haematological toxicity of grade 3/4 (common toxicity criteria) was seen in all courses. Renal tubular loss of electrolytes, particularly magnesium, occurred in 71% of cycles. Thirteen per cent of cycles were repeated within 21 days and 61% within 28 days. In the thirteen patients evaluable for response, a partial response rate of 31% was seen after two cycles. However, patients with stable disease continued on therapy, and an overall consequent response rate of 62% was observed. Four patients were alive with no evidence of disease at 8–74 months. Three are alive with disease (at 8–19 months). There were six deaths, all disease related. This regimen exhibits an encouraging response rate in a group of children with poor prognosis disease, with a tolerable toxicity profile. © 1999 Cancer Research Campaign PMID:10098754

  7. Combination of everolimus and tacrolimus: a potentially effective regimen for recalcitrant psoriasis.

    PubMed

    Wei, Kai-Che; Lai, Ping-Chin

    2015-01-01

    Severe forms of psoriasis that are refractory to conventional therapies are often difficult to manage. The mammalian target of rapamycin (mTOR) inhibitors potentially have versatile effects toward putative psoriatic pathologic pathways. Therefore, mTOR inhibitors may offer a range of new therapeutic options for patients with psoriasis. We describe a 55-year-old male renal transplant patient with refractory psoriasis. We adjusted his antirejection regimen and put him on everolimus (Certican(®); Novartis, Basel, Switzerland; a semisynthetic macrolide, belonging to the mTOR inhibitors family) with low-dose tacrolimus. This combination regimen maintained his graft function and successfully controlled his psoriasis. His skin lesions never recurred in the next 18 months. To our knowledge, this is the first report showing that the combination of everolimus and tacrolimus could be used to treat recalcitrant psoriasis. The relative benefit-risk profiles of such therapies worth further investigation.

  8. Optimal biologic dose of metronomic chemotherapy regimens is associated with maximum antiangiogenic activity.

    PubMed

    Shaked, Yuval; Emmenegger, Urban; Man, Shan; Cervi, Dave; Bertolini, Francesco; Ben-David, Yaacov; Kerbel, Robert S

    2005-11-01

    Low-dose metronomic chemotherapy is a promising therapeutic cancer treatment strategy thought to have an antiangiogenic basis. However, the advantages of reduced toxicity, increased efficacy in some cases, and ability to combine chemotherapy administered long term in this way with targeted therapies can be compromised by the empiricism associated with determining the optimum biologic dose (OBD). Using 4 distinct metronomic chemotherapy regimens in 4 different preclinical tumor models, including a hematologic malignancy, we established the OBD by determining the maximum efficacy associated with minimum or no toxicity. We then found each OBD to be strikingly correlated with the maximum reduction in viable peripheral blood circulating vascular endothelial growth factor receptor 2-positive (VEGFR-2+) endothelial precursors (CEPs). These results suggest that CEPs may serve as a pharmacodynamic biomarker to determine the OBD of metronomic chemotherapy regimens.

  9. Modelling and analysis of the feeding regimen induced entrainment of hepatocyte circadian oscillators using petri nets.

    PubMed

    Tareen, Samar Hayat Khan; Ahmad, Jamil

    2015-01-01

    Circadian rhythms are certain periodic behaviours exhibited by living organism at different levels, including cellular and system-wide scales. Recent studies have found that the circadian rhythms of several peripheral organs in mammals, such as the liver, are able to entrain their clocks to received signals independent of other system level clocks, in particular when responding to signals generated during feeding. These studies have found SIRT1, PARP1, and HSF1 proteins to be the major influencers of the core CLOCKBMAL1:PER-CRY circadian clock. These entities, along with abstracted feeding induced signals were modelled collectively in this study using Petri Nets. The properties of the model show that the circadian system itself is strongly robust, and is able to continually evolve. The modelled feeding regimens suggest that the usual 3 meals/day and 2 meals/day feeding regimens are beneficial with any more or less meals/day negatively affecting the system.

  10. Modelling and Analysis of the Feeding Regimen Induced Entrainment of Hepatocyte Circadian Oscillators Using Petri Nets

    PubMed Central

    Tareen, Samar Hayat Khan; Ahmad, Jamil

    2015-01-01

    Circadian rhythms are certain periodic behaviours exhibited by living organism at different levels, including cellular and system-wide scales. Recent studies have found that the circadian rhythms of several peripheral organs in mammals, such as the liver, are able to entrain their clocks to received signals independent of other system level clocks, in particular when responding to signals generated during feeding. These studies have found SIRT1, PARP1, and HSF1 proteins to be the major influencers of the core CLOCKBMAL1:PER-CRY circadian clock. These entities, along with abstracted feeding induced signals were modelled collectively in this study using Petri Nets. The properties of the model show that the circadian system itself is strongly robust, and is able to continually evolve. The modelled feeding regimens suggest that the usual 3 meals/day and 2 meals/day feeding regimens are beneficial with any more or less meals/day negatively affecting the system. PMID:25789928

  11. Clinical study of Mito-FLAG regimen in treatment of relapsed acute myeloid leukemia.

    PubMed

    Luo, Sheng; Cai, Fangfang; Jiang, Lei; Zhang, Shenghui; Shen, Zhijian; Sun, Lan; Gao, Shenmeng

    2013-03-01

    Patients with relapsed acute myeloid leukemia (AML) have unfavorable prognosis and require innovative therapeutic approaches. In this study we used fludarabine combined with a middle dose of cytosine arabinoside (Ara-C), mitoxantrone and granulocyte-colony stimulating factor (G-CSF) as a salvage therapy for patients with relapsed AML in China. Forty-five patients with relapsed AML were treated with the Mito-FLAG regimen consisting of mitoxantrone (7 mg/m(2), day 1, 3 and 5), fludarabine (30 mg/m(2), days 1-5), Ara-C (1 g/m(2), over 3 h every 12 h, days 1-5) and G-CSF [5 μg/kg/day subcutaneously from day 0 until the white blood count (WBC) was >20×10(9)/l]. Patients with a partial response (PR) received another course of the same regimen. Patients with a suitable donor and aged <50 years received allogeneic stem cell transplantation (allo-SCT). Twenty-three patients (51%) and 3 patients (7%) achieved complete remission (CR) and PR, respectively, following one or two courses of Mito-FLAG, and the overall response (OR) rate was 58%. Nine patients (20%) received allo-SCT and 4 patients (9%) succumbed early. Hematological toxicity and infections were the most prominent toxicities of this regimen. Other toxicities included nausea, vomiting, bleeding, hyperbilirubinemia, renal toxicity and arrhythmia. The probability of overall survival (OS) at 4 years was 19% (95% CI, 11-26%) and the probability of 4-year disease-free survival (DFS) was 29% for all 23 patients in CR (95% CI, 18-41%). Our data suggest that Mito-FLAG is a highly effective and well-tolerated salvage regimen for relapsed AML.

  12. Vildagliptin with metformin once-daily regimen-insights from a single-center analysis.

    PubMed

    Chatterjee, Sanjay; Chatterjee, Saurav

    2015-01-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitors have been well established as an adjunctive treatment to metformin. Most guidelines recommend treatment with a DPP-4 inhibitor, vildagliptin, in addition to metformin in a twice-daily regimen. However, the twice-daily regimen has difficulty with medication adherence, increased cost of therapy, and possibility of more side effects. Our objective was to evaluate, by means of retrospective analysis, the efficacy of once-daily metformin and vildagliptin (a DPP-4 inhibitor) in reducing blood glucose for patients on combination therapy. We analyzed data from our database of outpatients attending the diabetic clinic at a tertiary care center in Kolkata, India. We had data on once-daily combination of metformin and vildagliptin for 154 patients between September 2008 and May 2012. We followed up these patients for a median of 17.6 months and evaluated posttherapy glucose levels and hemoglobin A1c. Continuous variables were compared with t tests. Once-daily metformin-vildagliptin combination was found to be associated with a mean reduction of 27.52 mg/dL of fasting plasma glucose, 71.70 mg/dL of postprandial plasma glucose, and 1.41% reduction of HbA1c (P < 0.05 for all). Metformin-vildagliptin combination in a once-daily regimen seems to be associated with significant reductions in plasma glucose and HbA1c and may be a viable and cost-effective alternative to a twice-daily regimen as starting therapy.

  13. Intestinal Microbiota of Broiler Chickens As Affected by Litter Management Regimens

    PubMed Central

    Wang, Lingling; Lilburn, Mike; Yu, Zhongtang

    2016-01-01

    Poultry litter is a mixture of bedding materials and enteric bacteria excreted by chickens, and it is typically reused for multiple growth cycles in commercial broiler production. Thus, bacteria can be transmitted from one growth cycle to the next via litter. However, it remains poorly understood how litter reuse affects development and composition of chicken gut microbiota. In this study, the effect of litter reuse on the microbiota in litter and in chicken gut was investigated using 2 litter management regimens: fresh vs. reused litter. Samples of ileal mucosa and cecal digesta were collected from young chicks (10 days of age) and mature birds (35 days of age). Based on analysis using DGGE and pyrosequencing of bacterial 16S rRNA gene amplicons, the microbiota of both the ileal mucosa and the cecal contents was affected by both litter management regimen and age of birds. Faecalibacterium, Oscillospira, Butyricicoccus, and one unclassified candidate genus closely related to Ruminococcus were most predominant in the cecal samples, while Lactobacillus was predominant in the ileal samples at both ages and in the cecal samples collected at day 10. At days 10 and 35, 8 and 3 genera, respectively, in the cecal luminal microbiota differed significantly in relative abundance between the 2 litter management regimens. Compared to the fresh litter, reused litter increased predominance of halotolerant/alkaliphilic bacteria and Faecalibacterium prausnitzii, a butyrate-producing gut bacterium. This study suggests that litter management regimens affect the chicken GI microbiota, which may impact the host nutritional status and intestinal health. PMID:27242676

  14. TAC-TIC use of tacrolimus-based regimens in lupus nephritis.

    PubMed

    Kraaij, Tineke; Bredewold, Obbo W; Trompet, Stella; Huizinga, Tom W J; Rabelink, Ton J; de Craen, Anton J M; Teng, Y K Onno

    2016-01-01

    Current guidelines do not mention tacrolimus (TAC) as a treatment option and no consensus has been reported on the role of TAC in lupus nephritis (LN). The present study aimed to guide clinical judgement on the use of TAC in patients with LN. A meta-analysis was performed for clinical studies investigating TAC regimens in LN on the basis of treatment target (induction or maintenance), concomitant immunosuppression and quality of the data. 23 clinical studies performed in patients with LN were identified: 6 case series, 9 cohort studies, 2 case-control studies and 6 randomised controlled trials (RCTs). Of the 6 RCTs, 5 RCTs investigated TAC regimens as induction treatment and 1 RCT as maintenance treatment. Five RCTs investigated TAC in combination with steroids and 2 TAC with mycophenolate plus steroids. All RCTs were performed in patients of Asian ethnicity. In a meta-analysis, TAC regimens achieved a significantly higher total response (relative risk (RR) 1.23, 95% CI 1.12 to 1.34, p<0.05) and significantly higher complete response (RR 1.48, 95% CI 1.23 to 1.77, p<0.05). The positive outcome was predominantly defined by the largest RCT investigating TAC with mycophenolate plus steroids. Regarding safety, the occurrence of leucopoenia was significantly lower, while the occurrence of increased creatine was higher. Clinical studies on TAC regimens for LN are limited to patients of Asian ethnicity and hampered by significant heterogeneity. The positive results on clinical efficacy of TAC as induction treatment in LN cannot be extrapolated beyond Asian patients with LN. Therefore, further confirmation in multiethnic, randomised trials is mandatory. Until then, TAC can be considered in selected patients with LN.

  15. Do Glioma Patients Derive Any Therapeutic Benefit From Taking a Higher Cumulative Dose of Temozolomide Regimens?

    PubMed Central

    Sun, Hao; Du, Shasha; Liao, Guixiang; Xie, Xiao; Ren, Chen; Yuan, Ya Wei

    2015-01-01

    Abstract Temozolomide (TMZ) is an oral alkylating agent with established effects on the central nervous system of glioblastoma (GBM) patients. Clinical trials have demonstrated a significant impact on overall survival (OS) with TMZ. Ever since, several TMZ regimens have been designed to improve treatment efficacy by increasing the cumulative dose per cycle. We report a meta-analysis to systematically evaluate different treatment schedules of TMZ in GBM patients. All searches that were conducted in the Cochrane library, Science Direct, and PubMed Databases, and 3 randomized controlled trials (1141 patients) were included. OS and progression-free survival (PFS) were the primary outcomes to be pooled. Unexpectedly, this analysis did not reveal any OS or PFS advantage for the high cumulative dose (HCD) regimen compared with the normal cumulative dose regimen (1141 total patients; hazard ratio [HR] 1.07, 95% CI 0.94–1.22, P = 0.31). Then after analyzing the characteristics of the results from each trial, we found that the regimen with a higher peak concentration during a short-term period (daily doses ≥150 mg/m2/d within ≤7 days/cycle) always had a more superior clinical benefit. So we generated a new pooled HR of 1.10 with a 95% CI of 0.96–1.25 (P = 0.17), which prefers the high peak concentration schedule even without a significant difference. The adverse outcome also indicates a significant increased risk of leukopenia (risk ratio 1.59, 95% CI 1.03–2.46, P = 0.04) among the HCD group. Our study suggests that increasing the cumulative dose per cycle is not an ideal way to improve the efficacy of TMZ, and it will lead to increased risk for leukopenia. Future trials should be designed to examine schedules of higher peak concentration rather than the cumulative dose per cycle. PMID:25997057

  16. A Modified Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers

    DTIC Science & Technology

    2013-10-01

    regimen of two to three times daily while in a saturation environment. However, on two occasions during a 1000 feet of sea water ( fsw ) dry saturation...dive and during a 150 fsw dive in the U.S. Navy Saturation Flyaway Diving System (SATFADS), two different divers noted bilateral ear itching and...irritation. During the 1000 fsw dive, one diver reported bilateral ear itching and irritation of the left ear that was greater than the right ear on

  17. Drugs for treatment of vulvovaginal candidiasis: comparative efficacy of agents and regimens.

    PubMed

    Doering, P L; Santiago, T M

    1990-11-01

    Various agents are available for the treatment of vulvovaginal candidiasis. Imidazole agents (clotrimazole, miconazole, butoconazole, and terconazole) are preferred because of their greater efficacy, shorter treatment regimens, and ease of administration. Although the various imidazole compounds are equally efficacious, different treatment schedules are recommended depending on clinical situations. Additionally, different formulations are available that provide clinicians and patients with the opportunity to select the most appropriate agent.

  18. Combination regimens using doxorubicin and pegylated liposomal doxorubicin prior to autologous transplantation in multiple myeloma.

    PubMed

    Moreau, Philippe

    2009-07-01

    Doxorubicin and pegylated liposomal doxorubicin are key compounds of several induction regimens used prior to autologous stem cell transplantation in patients with de novo multiple myeloma, such as vincristine, doxorubicin, dexamethasone (VAD), vincristine, pegylated liposomal doxorubicin/Doxil, dexamethasone (DVd) or PS-341/bortezomib, doxorubicin, dexamethasone (PAD). The aim of this article is to summarize the more recent data available on the efficacy of these combinations and to discuss their role as part of initial therapy.

  19. TAC-TIC use of tacrolimus-based regimens in lupus nephritis

    PubMed Central

    Bredewold, Obbo W; Trompet, Stella; Huizinga, Tom W J; Rabelink, Ton J; de Craen, Anton J M; Teng, Y K Onno

    2016-01-01

    Current guidelines do not mention tacrolimus (TAC) as a treatment option and no consensus has been reported on the role of TAC in lupus nephritis (LN). The present study aimed to guide clinical judgement on the use of TAC in patients with LN. A meta-analysis was performed for clinical studies investigating TAC regimens in LN on the basis of treatment target (induction or maintenance), concomitant immunosuppression and quality of the data. 23 clinical studies performed in patients with LN were identified: 6 case series, 9 cohort studies, 2 case-control studies and 6 randomised controlled trials (RCTs). Of the 6 RCTs, 5 RCTs investigated TAC regimens as induction treatment and 1 RCT as maintenance treatment. Five RCTs investigated TAC in combination with steroids and 2 TAC with mycophenolate plus steroids. All RCTs were performed in patients of Asian ethnicity. In a meta-analysis, TAC regimens achieved a significantly higher total response (relative risk (RR) 1.23, 95% CI 1.12 to 1.34, p<0.05) and significantly higher complete response (RR 1.48, 95% CI 1.23 to 1.77, p<0.05). The positive outcome was predominantly defined by the largest RCT investigating TAC with mycophenolate plus steroids. Regarding safety, the occurrence of leucopoenia was significantly lower, while the occurrence of increased creatine was higher. Clinical studies on TAC regimens for LN are limited to patients of Asian ethnicity and hampered by significant heterogeneity. The positive results on clinical efficacy of TAC as induction treatment in LN cannot be extrapolated beyond Asian patients with LN. Therefore, further confirmation in multiethnic, randomised trials is mandatory. Until then, TAC can be considered in selected patients with LN. PMID:28123768

  20. Contribution of Oxazolidinones to the Efficacy of Novel Regimens Containing Bedaquiline and Pretomanid in a Mouse Model of Tuberculosis.

    PubMed

    Tasneen, Rokeya; Betoudji, Fabrice; Tyagi, Sandeep; Li, Si-Yang; Williams, Kathy; Converse, Paul J; Dartois, Véronique; Yang, Tian; Mendel, Carl M; Mdluli, Khisimuzi E; Nuermberger, Eric L

    2015-10-26

    New regimens based on two or more novel agents are sought to shorten or simplify treatment of tuberculosis (TB). Pretomanid (PMD) is a nitroimidazole in phase 3 trials that has significant bactericidal activity alone and in combination with bedaquiline (BDQ) and/or pyrazinamide (PZA). We previously showed that the novel combination of BDQ+PMD plus the oxazolidinone sutezolid (SZD) had sterilizing activity superior to that of the first-line regimen in a murine model of TB. The present experiments compared the activity of different oxazolidinones in combination with BDQ+PMD with or without PZA in the same model. The 3-drug regimen of BDQ+PMD plus linezolid (LZD) had sterilizing activity approaching that of BDQ+PMD+SZD and superior to that of the first-line regimen. The addition of PZA further enhanced activity. Reducing the duration of LZD to 1 month did not significantly affect the activity of the regimen. Halving the LZD dose or replacing LZD with RWJ-416457 modestly reduced activity over the first month but not after 2 months. AZD5847 and tedizolid also increased the bactericidal activity of BDQ+PMD, but they were less effective than the other oxazolidinones. These results provide optimism for safe, short-course oral regimens for drug-resistant TB that may also be superior to the current first-line regimen for drug-susceptible TB.

  1. Supralethal poisoning by any of the classical nerve agents is effectively counteracted by procyclidine regimens in rats.

    PubMed

    Myhrer, Trond; Mariussen, Espen; Enger, Siri; Aas, Pål

    2015-09-01

    A treatment regimen consisting of HI-6, levetiracetam, and procyclidine (termed the triple regimen) has previously been shown to work as a universal therapy against soman poisoning in rats, since it has capacities to function as both prophylactic and therapeutic measure. The purpose of the present study was to examine whether the triple regimen may have antidotal efficacy against intoxication by other classical nerve agents than soman. The treatment was given 1 and 5 min after exposure to a supralethal dose of nerve agents, and the results showed that the triple regimen successfully prevented or terminated seizures and preserved the lives of rats exposed to 5×LD50 of soman, sarin, cyclosarin, or VX, but solely 3×LD50 of tabun was managed by this regimen. To meet the particular antidotal requirements of tabun, the triple regimen was reinforced with obidoxime and was made to a quadruple regimen that effectively treated rats intoxicated by 5×LD50 of tabun. The rats recovered very well and the majority gained pre-exposure body weight within 7 days. Neuropathology was seen in all groups regardless of whether the rats seized or not. The most extensive damage was produced by sarin and cyclosarin. Differentiation between the nerve agents' potency to cause lesions was probably seen because the efficacious treatments ensured survival of supralethal poisoning. A combination of 2 oximes and 2 anticonvulsants may be a prerequisite to counteract effectively high levels of poisoning by any classical nerve agent.

  2. Fecal Bacterial Communities in treated HIV infected individuals on two antiretroviral regimens

    PubMed Central

    Pinto-Cardoso, Sandra; Lozupone, Catherine; Briceño, Olivia; Alva-Hernández, Selma; Téllez, Norma; Adriana, Aguilar; Murakami-Ogasawara, Akio; Reyes-Terán, Gustavo

    2017-01-01

    Intestinal microbiome changes that occur in HIV positive individuals on different antiretroviral therapy (ART) regimens are important to understand, as they are potentially linked with chronic inflammation and microbiome-linked comorbidities that occur at increased incidence in this population. We conducted a cross-sectional study comparing the fecal microbiomes of HIV-uninfected (HIV SN) to HIV-infected individuals on long-term ART (HIV+ LTART) from Mexico using 16S ribosomal RNA (16sRNA) targeted sequencing. These individuals were on two ART regimens based on either Non-Nucleoside Reverse Transcriptase Inhibitors (EFV) or ritonavir-boosted Protease Inhibitors (PI) with the same backbone of Nucleoside Reverse Transcriptase Inhibitors. Microbiome diversity was reduced in treated HIV infection compared to HIV SN (p < 0.05). Several operational taxonomic units (OTUs) related to the Ruminococcaceae family including Faecalibacterium prausnitzii were depleted in EFV and PI compared to HIV SN and negatively correlated with intestinal gut dysfunction as measured by the intestinal fatty binding protein (p < 0.05). This is the first report to address the fecal bacterial communities in HIV-infected individuals on two ARV regimens from Mexico. PMID:28262770

  3. Combined-modality therapy of rectal cancer with irinotecan-based regimens.

    PubMed

    Minsky, Bruce D

    2004-12-01

    There are two conventional treatments for clinically resectable rectal cancer. The first is surgery followed by postoperative combined-modality therapy if the tumor is T3 and/or N1/2. The second, if the tumor is ultrasound T3 or clinical T4, is preoperative combined-modality therapy followed by surgery and postoperative chemotherapy. There are a number of new chemotherapeutic agents that have been developed for the treatment of colorectal cancer. Phase I/II trials are examining the use of new chemotherapeutic agents in combination with pelvic radiation therapy, most commonly in the preoperative setting. There is considerable interest in integrating irinotecan (Camptosar) into preoperative combined-modality therapy regimens for rectal cancer. Based on these trials, the recommended regimen for patients who receive irinotecan-based combined-modality therapy is continuous infusion fluorouracil (5-FU), irinotecan, and pelvic radiation. New trials examining preoperative combined-modality therapy regimens substituting capecitabine (Xeloda) for continuous infusion 5-FU are in progress.

  4. Using clinically approved cyclophosphamide regimens to control the humoral immune response to oncolytic viruses

    PubMed Central

    Peng, K-W; Myers, R; Greenslade, A; Mader, E; Greiner, S; Federspiel, MJ; Dispenzieri, A; Russell, SJ

    2013-01-01

    Oncolytic viruses can be neutralized in the bloodstream by antiviral antibodies whose titers increase progressively with each exposure, resulting in faster virus inactivation and further reductions in efficacy with each successive dose. A single dose of cyclophosphamide (CPA) at 370 mg m−2 was not sufficient to control the primary antiviral immune responses in mice, squirrel monkeys and humans. We therefore tested clinically approved multidose CPA regimens, which are known to kill proliferating lymphocytes, to determine if more intensive CPA therapy can more effectively suppress antiviral antibody responses during virotherapy. In virus-susceptible mice, primary antibody responses to intravenously (i.v.) administered oncolytic measles virus (MV) or vesicular stomatitis virus (VSV) were partially or completely suppressed, respectively, by oral (1 mg × 8 days) or systemic (3 mg × 4 days) CPA regimens initiated 1 day before virus. When MV- or VSV-immune mice were re-challenged with the respective viruses and concurrently treated with four daily systemic doses of CPA, their anamnestic antibody responses were completely suppressed and antiviral antibody titers fell significantly below pre-booster levels. We conclude that the CPA regimen of four daily doses at 370 mg m−2 should be evaluated clinically with i.v. virotherapy to control the antiviral antibody response and facilitate effective repeat dosing. PMID:22476202

  5. Using clinically approved cyclophosphamide regimens to control the humoral immune response to oncolytic viruses.

    PubMed

    Peng, K-W; Myers, R; Greenslade, A; Mader, E; Greiner, S; Federspiel, M J; Dispenzieri, A; Russell, S J

    2013-03-01

    Oncolytic viruses can be neutralized in the bloodstream by antiviral antibodies whose titers increase progressively with each exposure, resulting in faster virus inactivation and further reductions in efficacy with each successive dose. A single dose of cyclophosphamide (CPA) at 370 mg m(-2) was not sufficient to control the primary antiviral immune responses in mice, squirrel monkeys and humans. We therefore tested clinically approved multidose CPA regimens, which are known to kill proliferating lymphocytes, to determine if more intensive CPA therapy can more effectively suppress antiviral antibody responses during virotherapy. In virus-susceptible mice, primary antibody responses to intravenously (i.v.) administered oncolytic measles virus (MV) or vesicular stomatitis virus (VSV) were partially or completely suppressed, respectively, by oral (1 mg × 8 days) or systemic (3 mg × 4 days) CPA regimens initiated 1 day before virus. When MV- or VSV-immune mice were re-challenged with the respective viruses and concurrently treated with four daily systemic doses of CPA, their anamnestic antibody responses were completely suppressed and antiviral antibody titers fell significantly below pre-booster levels. We conclude that the CPA regimen of four daily doses at 370 mg m(-2) should be evaluated clinically with i.v. virotherapy to control the antiviral antibody response and facilitate effective repeat dosing.

  6. Effect of an immunomodulatory regimen for cancer prevention: A case report

    PubMed Central

    Wang, Wenbo; Wang, Wei; Liu, Bing; Suo, Zhuoyao; Zhou, Lin; Liu, Guangxian

    2016-01-01

    In the present case study, an immunomodulatory regimen for cancer prevention is reported. A patient with an abnormally high level of the tumor markers, carbohydrate antigen-724 (CA724), CA19–9 and carcinoembryonic antigen (CEA), although without any detectable tumor, was treated with an immunomodulatory therapy featuring an infusion of cytokine-induced autologous killer cells (CIKs) at the request of the patient. Following the therapy, the three tumor markers rapidly decreased to below the normal reference level, although there still were slight fluctuations within a narrow range frequently. The patient was monitored for 21 months to the present day and no abnormality was observed. The results indicated that this therapy may be applied as a novel strategy that is effective and reliable for cancer prevention. As there is no promising regimen for the prevention of malignancies to date, such a treatment may become a major cancer prophylactic regimen, particularly for patients who are at a high risk of cancer. PMID:27900080

  7. Effectiveness of Once-Weekly Rifapentine and Moxifloxacin Regimens against Mycobacterium tuberculosis in Mice

    PubMed Central

    Lounis, Nacer; Bentoucha, Abdelhalim; Truffot-Pernot, Chantal; Ji, Baohong; O'Brien, Richard J.; Vernon, Andrew; Roscigno, Giorgio; Grosset, Jacques

    2001-01-01

    Mice infected with 1.6 × 107 CFU of Mycobacterium tuberculosis were treated 14 days later for 6 months with a regimen of once-weekly 10 mg of rifapentine and 75 mg of isoniazid per kg of body weight supplemented with either 150 mg of streptomycin per kg or 100 mg of moxifloxacin per kg during either both the 2-week daily initial and once-weekly continuation phases or only in the daily 2-week initial phase. On completion of treatment, all lung cultures were negative, except for three mice, each with a single colony: two whose rifapentine-isoniazid regimen was supplemented with streptomycin during the whole course of therapy and one whose rifapentine-isoniazid regimen had no initial daily phase, but was supplemented with streptomycin and moxifloxacin during the whole course of therapy. After 3 months of follow-up, positive lung cultures were obtained from 61 and 56% of mice supplemented with streptomycin during either the full course of therapy or only the daily 2-week initial phase, respectively, and 15 and 50% of mice supplemented with moxifloxacin during either the full course of therapy or only the daily 2-week initial phase, respectively. These results suggest that moxifloxacin has sterilizing activity against M. tuberculosis. PMID:11709328

  8. Effects of the Yuzpe regimen, given during the follicular phase, on ovarian function.

    PubMed

    Croxatto, H B; Fuentealba, B; Brache, V; Salvatierra, A M; Alvarez, F; Massai, R; Cochon, L; Faundes, A

    2002-02-01

    This study was conducted to assess to what extent the Yuzpe regimen, or half the dose, given in the follicular phase, prevents ovulation during the ensuing 5 days. Sixty women were divided into six groups. All groups received placebo in one cycle and drug in another, in a randomized order. Groups differed by the dose and size of the leading follicle at the time of treatment (12-14, 15-17, or 18-20 mm). Ovulation was absent during the ensuing 5 days in 13 of 20 participants (65%) and in 8 of 20 participants (40%) who received the full and the half dose, respectively, when follicles were 12-17 mm. No ovulation occurred, within the critical period, in 7 of 39 placebo cycles (18%). When follicles were 18-20 mm, treatment did not prevent ovulation. In most drug-treated cycles, plasma gonadotropin and sex steroid levels were significantly depressed within the 5-day period, even when follicular rupture occurred within that period. In conclusion, the Yuzpe regimen can suppress or postpone ovulation to an extent that exceeds the fertile life of spermatozoa. Lack of ovulation within the critical period and dysfunction of the ovulatory process probably account for the contraceptive effect of this method in most cases. The present data do not warrant the use of half the dose of the Yuzpe regimen.

  9. Influence of feeding regimens on rat gut fluids and colonic metabolism of diclofenac-β-cyclodextrin.

    PubMed

    Vieira, Amélia C F; Murdan, Sudaxshina; Serra, Arménio C; Veiga, Francisco J; Gonsalves, António M d'A Rocha; Basit, Abdul W

    2014-11-04

    Feeding states may affect the performance of colonic prodrugs. The aim is to investigate the influence of feeding regimen in Wistar rats on: (i) distribution and pH contents along the gut and (ii) metabolism of two colonic prodrugs, diclofenac-β-cyclodextrin and a commercially available control, sulfasalazine, within the caecal and colonic contents. Male Wistar rats were subject to four different feeding regimens, the gut contents characterized (mass and pH) and the metabolism of prodrugs investigated. The feeding regimen affects gut contents (mass and pH), more specifically in the stomach and lower intestine, and affects the rate of metabolism of diclofenac-β-cyclodextrin, but not that of sulfasalazine. The latter's degradation is much faster than that of diclofenac-β-cyclodextrin while the metabolism of both prodrugs is faster in colonic (versus caecal) contents. Fasting results in most rapid degradation of diclofenac-β-cyclodextrin, possibly due to lack of competition (absence of food) for microbial enzymatic activity.

  10. Allogeneic stem cell transplantation for severe acquired aplastic anaemia using a fludarabine-based preparative regimen.

    PubMed

    Resnick, Igor B; Aker, Memet; Shapira, Michael Y; Tsirigotis, Panagiotis D; Bitan, Menachem; Abdul-Hai, Ali; Samuel, Simcha; Ackerstein, Aliza; Gesundheit, Benjamin; Zilberman, Irina; Miron, Svetlana; Yoffe, Luba; Lvovich, Alex; Slavin, Shimon; Or, Reuven

    2006-06-01

    We reviewed our experience in the treatment of 13 patients with severe acquired aplastic anaemia, using a newly developed non-myeloablative regimen consisting of fludarabine (total dose 180 mg/m2), cyclophosphamide (total dose 120 mg/kg), and antithymocyte globulin (total dose 40 mg/kg). All except one patient received multiple transfusions and had failed prior immunosuppressive treatment. Twelve out of 13 patients achieved sustained engraftment. One patient was not evaluable for engraftment because of early death on day +10. None of the patients developed graft failure. Mucositis of mild-to-moderate severity was the only observed regimen-related toxicity. The cumulative incidence of acute graft-versus-host disease (GvHD) grade II-IV and III-IV was 8.3% and 0%, respectively. With a median follow-up period of 45 months, the 5-year overall survival probability was 84%. Eight out of 11 surviving patients have been followed for more than 1 year and only one developed limited chronic GvHD. All patients enjoy a normal life style, with a Karnofsky score of 100%, and all except three, followed for 3, 5 and 6 months respectively, are free of any immunosuppressive medication. The results of this study look promising, while prospective clinical trials may be required to confirm the benefits of this regimen as an alternative to existing protocols.

  11. A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa

    PubMed Central

    Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

    2015-01-01

    Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (Isc). Subsequent Isc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. Isc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation. PMID:26038704

  12. Ofloxacin containing combined drug regimens in the treatment of multibacillary leprosy.

    PubMed

    Sampoonachot, P; Bundit, C; Kuhacharoen, N; Peerapakorn, S; Kampirapap, K; Poomlek, A; Bampenyu, S; Tiasiri, S; Rungruang, S; Surasondhi, S; Supanwanit, S; Wiriyawipart, S

    1997-12-01

    The results of ofloxacin containing combined drug regimens in the treatment of 60 multibacillary leprosy cases from January 1989 to June 1995 are reported. The objective of the trial is to compare the antileprotic property of ofloxacin and rifampicin in multibacillary leprosy patients and to study the killing rate of M. leprae by ofloxacin and rifampicin before mass treatment can be recommended. The complications and side-effects of ofloxacin and rifampicin were of a mild nature and both drugs were well tolerated. Moderate to marked clinical improvement was noticed in a short period with ofloxacin containing regimens in multibacillary leprosy patients. No persisters were detected in any of the 33 specimens (of mouse footpads) that had been obtained after treatment for 6 months. Ofloxacin if added to the currently used WHO recommended MB-MDT regimen may shorten the duration of treatment. Ofloxacin, therefore, may be considered as a suitable alternative in suspected/proven rifampicin resistant cases and where rifampicin is contraindicated. The results were evaluated on the basis of the clinical conditions, mycobactericidal effectiveness, signs of drug toxicity and side effects.

  13. Evaluation of Blood Regimen on the Survival of Cimex lectularius L. Using Life Table Parameters

    PubMed Central

    Barbarin, Alexis M; Gebhardtsbauer, Ron; Rajotte, Edwin G.

    2013-01-01

    Knowledge of bed bug development under varying conditions can lead to more sophisticated management techniques. Development rate, age and stage-specific life tables were compared for a laboratory strain (HS) and field strain (ECL-05) of bed bug Cimex lectularius L. (Hemiptera: Heteroptera) reared on two blood regimens: human or rabbit blood. Harlan and ECL-05 bed bugs reared on human blood had a life expectancy of 207 and 208 days respectively from the egg stage. Egg to adult development of HS bed bugs reared on human blood (~35 days) was significantly longer than that of the ECL-05 strain (~33 days) in the third, fourth, and fifth instars. The HS and ECL-05 bed bugs reared on rabbit blood had a life expectancy of 149 and 174 days respectively. Egg to adult development time of HS on rabbit blood (~52 days) was significantly longer than ECL-05 (~37 days) in every instar, and HS total life span was significantly shorter compared to ECL-05. Developmental differences based on strain and blood regimen suggest rabbit blood is an inferior blood source for colony maintenance, and strain has variable effects on bed bug development. Findings suggest that blood regimen should strongly be considered in bed bug colony maintenance. PMID:26464390

  14. Fecal Bacterial Communities in treated HIV infected individuals on two antiretroviral regimens.

    PubMed

    Pinto-Cardoso, Sandra; Lozupone, Catherine; Briceño, Olivia; Alva-Hernández, Selma; Téllez, Norma; Adriana, Aguilar; Murakami-Ogasawara, Akio; Reyes-Terán, Gustavo

    2017-03-06

    Intestinal microbiome changes that occur in HIV positive individuals on different antiretroviral therapy (ART) regimens are important to understand, as they are potentially linked with chronic inflammation and microbiome-linked comorbidities that occur at increased incidence in this population. We conducted a cross-sectional study comparing the fecal microbiomes of HIV-uninfected (HIV SN) to HIV-infected individuals on long-term ART (HIV+ LTART) from Mexico using 16S ribosomal RNA (16sRNA) targeted sequencing. These individuals were on two ART regimens based on either Non-Nucleoside Reverse Transcriptase Inhibitors (EFV) or ritonavir-boosted Protease Inhibitors (PI) with the same backbone of Nucleoside Reverse Transcriptase Inhibitors. Microbiome diversity was reduced in treated HIV infection compared to HIV SN (p < 0.05). Several operational taxonomic units (OTUs) related to the Ruminococcaceae family including Faecalibacterium prausnitzii were depleted in EFV and PI compared to HIV SN and negatively correlated with intestinal gut dysfunction as measured by the intestinal fatty binding protein (p < 0.05). This is the first report to address the fecal bacterial communities in HIV-infected individuals on two ARV regimens from Mexico.

  15. Evaluating the Effect of Zingiber Officinalis on Nausea and Vomiting in Patients Receiving Cisplatin Based Regimens

    PubMed Central

    Fahimi, Fanak; Khodadad, Kian; Amini, Somayeh; Naghibi, Farzaneh; Salamzadeh, Jamshid; Baniasadi, Shadi

    2011-01-01

    Ginger, the rhizome of Zingiber officinalis, has long been used as herbal medicine for its antiemetic effect. For evaluating the effect of zingiber officinalis on nausea and vomiting (N and V) in patients receiving cisplatin based regimens, a randomized double-blind placebo-controlled cross-over clinical trial was carried out in patients receiving cisplatin in combination with other chemotherapeutic agents. The patients were randomly assigned to receive ginger capsules (rhizome of zingiber officinalis) or placebo in their first cycle of the study. All patients received standard antiemetics for chemotherapy induced nausea and vomiting (CINV). The patients were crossed-over to receive ginger or placebo in their next cycle of chemotherapy. Among 36 eligible patients who received both cycles of treatment, there were no difference in prevalence, severity, and duration of both acute and delayed N and V. Addition of ginger to the standard antiemetic regimen has shown no advantage in reducing acute and delayed N and V in patients with cisplatin-based regimen in this study. PMID:24250368

  16. Efficacy of traditional treatment regimen on Kati Shoola with special reference to lumbar spondylolisthesis.

    PubMed

    Ediriweera, E R H S S; Gunathilka, H D P; Weerasinghe, K D C M; Kalawana, O T M R K S B

    2013-01-01

    According to Ayurveda, Kati Shoola is a disease with pain in lumbar region. Lumbar spondylolisthesis, anterior displacement of a vertebra or the vertebral column in relation to the vertebrae below, is one of the common causes. Current case study was carried out at Ayurveda Teaching hospital, Borella, to evaluate the efficacy of a treatment regimen used by Sri Lankan traditional physician family "Weerasinghe." A 59-year-old female with a 9-month history of lumbar spondylolisthesis was treated with this regimen. The patient had progressive pain in left lower back, right and left buttocks, and difficulty in bending forward over 5°. X-ray of lumbo sacral region indicated that patient was suffering from Grade 3 lumbar spondylolisthesis. She was treated for 65 days with four treatment packages consisting of 13 prepared medicines. The response to the treatment was recorded and therapeutic effects were evaluated through symptomatic relief. Clinical symptoms were significantly reduced and degree of anterior flexion increased from 5° to 90°. However, X-rays indicated that the patient was still suffering from Grade 3 lumbar spondylolisthesis. This regimen is effective in successfully treating Kati Shoola (lumbar spondylolisthesis) by helping to reduce the symptoms and improving the degree of anterior flexion.

  17. Efficacy of traditional treatment regimen on Kati Shoola with special reference to lumbar spondylolisthesis

    PubMed Central

    Ediriweera, E. R. H. S. S.; Gunathilka, H. D. P.; Weerasinghe, K. D. C. M.; Kalawana, O. T. M. R. K. S. B.

    2013-01-01

    According to Ayurveda, Kati Shoola is a disease with pain in lumbar region. Lumbar spondylolisthesis, anterior displacement of a vertebra or the vertebral column in relation to the vertebrae below, is one of the common causes. Current case study was carried out at Ayurveda Teaching hospital, Borella, to evaluate the efficacy of a treatment regimen used by Sri Lankan traditional physician family “Weerasinghe.” A 59-year-old female with a 9-month history of lumbar spondylolisthesis was treated with this regimen. The patient had progressive pain in left lower back, right and left buttocks, and difficulty in bending forward over 5°. X-ray of lumbo sacral region indicated that patient was suffering from Grade 3 lumbar spondylolisthesis. She was treated for 65 days with four treatment packages consisting of 13 prepared medicines. The response to the treatment was recorded and therapeutic effects were evaluated through symptomatic relief. Clinical symptoms were significantly reduced and degree of anterior flexion increased from 5° to 90°. However, X-rays indicated that the patient was still suffering from Grade 3 lumbar spondylolisthesis. This regimen is effective in successfully treating Kati Shoola (lumbar spondylolisthesis) by helping to reduce the symptoms and improving the degree of anterior flexion. PMID:24049411

  18. A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa.

    PubMed

    Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

    2015-03-01

    Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (I sc). Subsequent I sc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. I sc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation.

  19. The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study

    PubMed Central

    2013-01-01

    Objective To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes. Design Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration. Methods Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the ‘intention-to-treat’ effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting. Results A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/μl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens. Conclusions Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine. PMID:22546987

  20. Four-Month Moxifloxacin-Based Regimens for Drug-Sensitive Tuberculosis

    PubMed Central

    Gillespie, Stephen H.; Crook, Angela M.; McHugh, Timothy D.; Mendel, Carl M.; Meredith, Sarah K.; Murray, Stephen R.; Pappas, Frances; Phillips, Patrick P.J.; Nunn, Andrew J.

    2014-01-01

    BACKGROUND Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis. METHODS We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization. RESULTS Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group. CONCLUSIONS The two moxifloxacin

  1. Effect of heat treatment on the antioxidant activity, color, and free phenolic acid profile of malt.

    PubMed

    Inns, Elizabeth L; Buggey, Lesley A; Booer, Christopher; Nursten, Harry E; Ames, Jennifer M

    2007-08-08

    Green malt was kilned at 95 degrees C following two regimens: a standard regimen (SKR) and a rapid regimen (RKR). Both resulting malts were treated further in a tray dryer heated to 120 degrees C, as was green malt previously dried to 65 degrees C (TDR). Each regimen was monitored by determining the color, antioxidant activity (by both ABTS(.+) and FRAP methods), and polyphenolic profile. SKR and RKR malts exhibited decreased L* and increased b* values above approximately 80 degrees C. TDR malts changed significantly less, and color did not develop until 110 degrees C, implying that different chemical reactions lead to color in those malts. Antioxidant activity increased progressively with each regimen, although with TDR malts this became significant only at 110-120 degrees C. The RKR malt ABTS(.+) values were higher than those of the SKR malt. The main phenolics, that is, ferulic, p-coumaric, and vanillic acids, were monitored throughout heating. Ferulic acid levels increased upon heating to 80 degrees C for SKR and to 70 degrees C for RKR, with subsequent decreases. However, the levels for TDR malts did not increase significantly. The increase in free phenolics early in kilning could be due to enzymatic release of bound phenolics and/or easier extractability due to changes in the matrix. The differences between the kilning regimens used suggest that further modification of the regimens could lead to greater release of bound phenolics with consequent beneficial effects on flavor stability in beer and, more generally, on human health.

  2. A randomized, controlled trial of tea tree topical preparations versus a standard topical regimen for the clearance of MRSA colonization.

    PubMed

    Dryden, M S; Dailly, S; Crouch, M

    2004-04-01

    Two topical MRSA eradication regimes were compared in hospital patients: a standard treatment included mupirocin 2% nasal ointment, chlorhexidine gluconate 4% soap, silver sulfadiazine 1% cream versus a tea tree oil regimen, which included tea tree 10% cream, tea tree 5% body wash, both given for five days. One hundred and fourteen patients received standard treatment and 56 (49%) were cleared of MRSA carriage. One hundred and ten received tea tree oil regimen and 46 (41%) were cleared. There was no significant difference between treatment regimens (Fisher's exact test; P = 0.0286). Mupirocin was significantly more effective at clearing nasal carriage (78%) than tea tree cream (47%; P = 0.0001) but tea tree treatment was more effective than chlorhexidine or silver sulfadiazine at clearing superficial skin sites and skin lesions. The tea tree preparations were effective, safe and well tolerated and could be considered in regimens for eradication of MRSA carriage.

  3. Confirmation of factors that influence antiretroviral regimen change and the subsequent patient outcomes at a Regional Hospital in rural KwaZulu-Natal

    PubMed Central

    Naidoo, Panjasaram

    2016-01-01

    Background Treatment failure (TF) and adverse drug reactions (ADRs) are the main indications for antiretroviral therapy (ART) regimen change. Identification of factors influencing regimen change and subsequent health outcomes of patients after regimen change is essential in providing a sustainable and effective antiretroviral roll-out campaign. Aim To confirm the factors that influence antiretroviral regimen change and to evaluate patient outcomes post regimen change. Methods A retrospective chart analysis of 269 HIV-infected non-pregnant patients (age >18 years), who underwent an antiretroviral (ARV) regimen change and were followed up for approximately one year since initiation, was undertaken at a Provincial Hospital ARV Clinic in KwaZulu-Natal, from January 2008 to December 2012. Results Of the 269 patients, there were 200 females (75%). Most patients were between the ages 30 and 44 (57.6%). Only five patients had coexisting tuberculosis (TB) infection (2%). The most common first-line ART regimen to be changed was stavudine (D4T)/lamivudine(3TC)/ efavirenz(EFV) n = 111(41%). The most common regimen patients were changed to was tenofovir (TDF)/3TC/EFV n = 89(33%). Stavudine was the most commonly substituted drug (35.5%). Lipodystrophy was the most common ADR (56.8%). ADR was the indication for ART regimen change in 175 patients (65%), whilst TF accounted for ART regimen change in 94 patients (35%). Immunological success (CD4 counts) was shown after regimen change (374.21 ± 243.16 vs. 456.09 ± 250.07, CI: 0.95, p < 0.001). Undetectable viral loads were measured in 172/205 (83.9%) patients post regimen change. Conclusion ADRs were the main cause for antiretroviral regimen change. Stavudine was the most substituted drug with lipodystrophy being the most common side effect. Coexisting TB infection did not influence regimen change. Immunological and virological success was shown after regimen modification. PMID:28155312

  4. A national survey of the chemotherapy regimens used to treat small cell lung cancer (SCLC) in the United Kingdom.

    PubMed

    Sambrook, R J; Girling, D J

    2001-06-01

    Many chemotherapy regimens are used for treating SCLC in the United Kingdom, but it is not known, in any detail, which regimens are used, by which specialists, for which types of patient. We conducted a survey among all medical and clinical oncologists, respiratory physicians and general physicians with respiratory interest in the United Kingdom to find out. The questionnaire asked for the number of SCLC patients treated annually; how many were given chemotherapy; the drugs, doses and schedules chosen according to prognostic group (as defined by the clinician); and the reasons for choice of regimen. 1214 questionnaires were sent out, and responses were received from 1070 (88%) clinicians; 266 (25%) of these treated SCLC with chemotherapy. Of 4674 patients given chemotherapy annually, 36% were given it by clinical oncologists, 30% by medical oncologists, 27% by respiratory physicians, and 7% by general physicians. In all, 34 regimens were reported with 151 different combinations of dose and schedule. In 2311 good prognosis patients, 23 regimens were used, the commonest being ACE (doxorubicin, cyclophosphamide, etoposide), ICbE (ifosfamide, carboplatin, etoposide), CAV (cyclophosphamide, doxorubicin, vincristine), CbE (carboplatin, etoposide), and PE (cisplatin, etoposide). In 1517 poor prognosis patients, 21 regimens were used, the commonest being CAV, EV (etoposide, vincristine), CbE, CAV alternating with PE, and oral etoposide. 452 patients were treated regardless of prognosis and for 219 no prognostic criteria were specified. The remaining 175 were given second-line chemotherapy or were given regimens chosen to avoid toxicity or because of intercurrent disease or other reasons. The main reasons affecting choice of regimen were routine local practice, patients' convenience, quality of life considerations, trial results and cost. The results show wide variation in routine practice and will be useful in reporting and planning clinical trials and in deciding on local

  5. Vonoprazan-Based Regimen Is More Useful than PPI-Based One as a First-Line Helicobacter pylori Eradication: A Randomized Controlled Trial

    PubMed Central

    Tanaka, Naoki; Kubota, Daisuke; Miyajima, Masayuki; Tokutake, Koujiro; Imai, Ryujiro; Fujisawa, Toru; Mori, Hiromitsu; Matsuda, Yoshiaki; Wada, Shuichi; Horiuchi, Akira; Kiyosawa, Kendo

    2017-01-01

    Background. A new agent, potassium-competitive acid blocker vonoprazan (VPZ) has potent acid-inhibitory effects and may offer advantages over conventional H. pylori eradication therapies. We aimed to compare the eradication rate between VPZ-based treatment and PPI-based one. Methods. This randomized controlled trial was designed to assign 141 patients with H. pylori-positive gastritis to VPZ group (VPZ 20 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg twice daily for 7 days) or PPI group (rabeprazole 20 mg or lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg twice daily for 7 days). Primary endpoints were eradication rates and adverse events. Results. Seventy of 72 patients in VPZ group and 63 of 69 patients in PPI group completed the treatment after 7 days. The eradication rate was significantly higher in VPZ group than PPI group by intention-to-treat analysis (95.8% versus 69.6%, P = 0.00003, 95% confidence interval [CI] 88.3-99.1% versus 57.3-80.1%) and per-protocol analysis (95.7% versus 71.4%, P = 0.0002, 95% CI 88.0-99.1% versus 58.7-82.1%). The incidence of adverse events was not different between the groups (26.3% in VPZ group versus 37.7% in PPI group, P = 0.15). Conclusion. VPZ-based regimen is more useful than that PPI-based regimen as a first-line H. pylori eradication therapy. PMID:28349044

  6. Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in children with sickle cell disease.

    PubMed

    Strocchio, Luisa; Zecca, Marco; Comoli, Patrizia; Mina, Tommaso; Giorgiani, Giovanna; Giraldi, Eugenia; Vinti, Luciana; Merli, Pietro; Regazzi, Mario; Locatelli, Franco

    2015-06-01

    Although allogeneic haematopoietic stem cell transplantation (HSCT) still represents the only consolidated possibility of cure for sickle cell disease (SCD) patients, its use has been limited by the risk of morbidity and mortality associated with conventional myeloablative therapy. The introduction of treosulfan to replace busulfan in conditioning regimens has recently been explored by virtue of its lower toxicity profile. We report our experience with a treosulfan/thiotepa/fludarabine conditioning for human leucocyte antigen (HLA)-matched sibling or unrelated donor-HSCT in 15 children with SCD, and compare patient outcomes with those of a historical cohort (15 patients) given a busulfan-based regimen. Engraftment was achieved in 28 out of 30 patients (93%), with one case of graft failure in either group. The conditioning regimen was well tolerated in both groups, with no cases of grade III-IV regimen-related toxicity. The 7-year overall survival (OS) and disease-free survival (DFS) for the whole cohort were 100% and 93%, respectively, with a 93% DFS in both busulfan and treosulfan groups. No SCD-related adverse events occurred after engraftment in patients with complete or mixed donor chimerism. This retrospective analysis suggests that a treosulfan-based conditioning regimen is able to ensure engraftment with excellent OS/DFS and low regimen-related toxicity in patients with SCD.

  7. Consolidative therapy with stem cell transplantation improves survival of patients with mantle cell lymphoma after any induction regimen.

    PubMed

    Reddy, Nishitha; Greer, John P; Goodman, Stacey; Kassim, Adetola; Morgan, David S; Chinratanalab, Wichai; Brandt, Stephen; Englehardt, Brian; Oluwole, Olalekan; Jagasia, Madan H; Savani, Bipin N

    2012-05-01

    Intensive induction regimen followed by high-dose chemotherapy and autologous stem cell transplantation (auto-SCT) is frequently used to improve outcomes in patients with mantle-cell lymphoma. The comparative impact of conventional vs intensive induction regimen before transplantation is unknown. Forty-eight patients with mantle-cell lymphoma receiving SCT at our institution between January 2000 and December 2010 were included in this study. At the time of initial presentation, 43 (89.5%) had stage IV disease and 18 (37.5%) received more than one chemotherapy regimen before transplantation. Forty patients underwent auto-SCT and 7 had allogeneic SCT (allo-SCT); 1 patient had an allo-SCT for relapsed disease after auto-SCT. At the time of this analysis (median follow-up of 6 years from diagnosis and 4 years from transplantation), 40 patients (88%) were alive with a 5-year disease-free survival of 74.8%. Age, disease stage, number of regimens pre-SCT, pre-SCT disease status, and type of SCT had no impact on long-term outcomes. Importantly, there were no differences among the types of induction regimen on outcomes in this cohort receiving SCT. Based on our data, we believe that future studies should focus on strategies to prevent disease relapse rather than comparing induction regimens before stem cell transplantation.

  8. The effect of surface treatments and bonding regimens on microtensile bond strengths of repaired composite: An in vitro study

    PubMed Central

    Acharya, Gouri Smita; Manjunath, MK

    2012-01-01

    Aim: To assess the microtensile bond strength of repaired composite resin that was surface treated by diamond point or silicon carbide followed by bonding using either only total- etch bonding regimen or silane coupling agent with adhesive resin. Materials and Methods: Fourteen composite blocks were aged under deionized water for 14 days. The bonding surface was prepared with coarse diamond point or silicon carbide. Two blocks with no surface treatment were used as control groups. The bonding regimen was either total-etch bonding regimen or silane coupling agent and bonding agent. The aged samples were then bonded to new composite. Five sections per block (each 1mm thick) were prepared; cut to obtain an adhesive zone of approximately 1mm2 and subjected to microtensile bond strength testing. Results: The highest bond strength was obtained by surface treatment by coarse diamond point and total etch bonding regimen and least by silicon carbide and silane. A statistically significant difference was seen in all the four groups. Conclusions: Surface treatment by a coarse diamond point and total-etch bonding regimen provides highest bond strength. Thus, a simpler treatment regimen can contribute to a better bond strength in repaired composites. PMID:23112489

  9. Successful engraftment of mismatched unrelated cord blood transplantation following reduced intensity preparative regimen using fludarabine and busulfan.

    PubMed

    Komatsu, Tsunehiko; Narimatsu, Hiroto; Yoshimi, Ai; Kurita, Naoki; Kusakabe, Manabu; Hori, Akiko; Murashige, Naoko; Matsumura, Tomoko; Kobayashi, Kazuhiko; Yuji, Koichiro; Tanaka, Yuji; Kami, Masahiro

    2007-01-01

    We conducted a pilot study to evaluate the feasibility of reduced-intensity cord blood transplantation (RI-CBT) using a non-total body irradiation (TBI) regimen in adult patients with advanced hematologic malignancies. Seventeen patients with a median age of 58 years (range, 38-74) underwent RI-CBT at Tsukuba Memorial Hospital between April 2004 and November 2005. Preparative regimens were fludarabine 30 mg/m(2) for 6 days, and busulfan 4 mg/kg for 2 days. Tacrolimus was used for prophylaxis of graft-vs-host disease (GVHD). Median numbers of infused total nucleated were 2.6 x 10(7)/kg (range, 2.0-3.3). HLA disparity was found in 2/6 antigens (n=16) and 1/6 antigens (n=1). Underlying diseases progressed despite preparative regimens in four patients. Of the remaining 13 patients, nine patients achieved engraftment at a median of day 18 (range, 17-28). Six of the nine patients with engraftment achieved complete donor-type chimerism by day 100. Six patients were alive in remission at median follow-up of 13.1 months (range, 1.0-19.0). This study demonstrated the feasibility of RI-CBT using a non-TBI regimen in adults. When disease progression is controlled by the preparative regimen, RI-CBT carries a clinically significant graft-vs-tumor effect. Further studies are required to identify patients who benefit from this regimen.

  10. The effects of pullet body weight, dietary nonpyhtate phosphorus intake, and breeder feeding regimen on production performance, chick quality, and bone remodeling in broiler breeders.

    PubMed

    Ekmay, R D; Salas, C; England, J; Cerrate, S; Coon, C N

    2012-04-01

    A 3 × 2 × 2 factorial experiment, consisting of 52 hens per treatment, was conducted to determine the effects of pullet BW, dietary nonphytate phosphorus (NPP), and feeding regimen on performance, progeny quality, and bone remodeling. Cobb 500 broiler breeder pullets were reared to 3 different growth curves: 20% under, Cobb standard, and 20% over. Body weights were recorded weekly and feed adjustments made accordingly. At 21 wk, 624 hens were fed one of 2 breeder diets differing only in the amount of dietary NPP: 0.15 or 0.40%. A normal feeding regimen was appropriate for the particular growth curve; an alternative regimen considered the 3 growth curves together as a flock. At 24, 26, and 29 wk, blood was collected from 5 hens per treatment every 4 h over a 24-h period. Plasma samples were analyzed for total alkaline phosphatase, tartrate-resistant acid phosphatase, parathyroid hormone-related peptide, Ca, and inorganic P. Eggs per hen housed were diminished in hens fed the low dietary NPP and by low pullet target weight. Hens fed low dietary NPP also had lower egg weights but better eggshell quality. Mortality was significantly higher in hens fed low dietary NPP. Breeder tibia relative strength and ash were also significantly lower in hens fed low dietary NPP, regardless of the quantitative amount. Progeny tibia ash was not affected by any treatment. Total alkaline phosphatase responded to pullet BW, however by wk 29, total alkaline phosphatase also became sensitive to dietary NPP. The NPP by pullet BW interaction for tartrate-resistant acid phosphatase levels became significant by 29 wk, and pullet BW was significant at wk 24. The NPP by pullet growth curve interaction was also critical for plasma inorganic P levels throughout the sampling period. In summary, both 0.15% dietary NPP and reared pullets 20% under standard BW negatively affect egg production but do not impair progeny productivity. Body composition appears to be a main contributor in bone remodeling

  11. Penicillins vs trimethoprim-based regimens for acute bacterial exacerbations of chronic bronchitis

    PubMed Central

    Korbila, Ioanna P.; Manta, Katerina G.; Siempos, Ilias I.; Dimopoulos, George; Falagas, Matthew E.

    2009-01-01

    ABSTRACT OBJECTIVE To compare the effectiveness and toxicity of semisynthetic penicillins (SSPs) (amoxicillin, ampicillin, pivampicillin) and trimethoprim-based regimens (trimethoprim, trimethoprim-sulfamethoxazole, trimethoprim-sulfadiazine) in treating acute bacterial exacerbations of chronic bronchitis (ABECB). DATA SOURCES We searched MEDLINE, EMBASE, Current Contents, and the Cochrane Central Register of Controlled Trials to identify and extract data from relevant randomized controlled trials (RCTs). STUDY SELECTION Only RCTs comparing penicillins with trimethoprim-based regimens for the treatment of patients with ABECB that reported data on effectiveness, toxicity, or mortality were considered eligible for this meta-analysis. SYNTHESIS Out of 134 RCTs identified in the search, 5 RCTs involving 287 patients were included in the analysis. There were no differences between patients with ABECB treated with SSPs and those treated with trimethoprim, alone or in combination with a sulfonamide, in treatment success (intention-to-treat patients: n = 262, odds ratio [OR] 1.68, 95% confidence interval [CI] 0.91–3.09; clinically evaluable patients: n = 246, OR 1.59, 95% CI 0.79–3.20) or number of drug-related adverse events in general (n = 186 patients, OR 0.37, 95% CI 0.11–1.24), frequency of diarrhea or skin rashes, or number of withdrawals due to adverse events (n = 179 patients, OR 0.27, 95% CI 0.07–1.03). CONCLUSION Based on limited evidence leading to wide CIs of the estimated treatment effects, SSPs and trimethoprim-based regimens seem to be equivalent in terms of effectiveness and toxicity for ABECB. PMID:19155372

  12. Transzonular vitreous injection vs a single drop compounded topical pharmaceutical regimen after cataract surgery

    PubMed Central

    Fisher, Bret L; Potvin, Rick

    2016-01-01

    Purpose To compare the relative effectiveness of a Tri-Moxi-Vanc intraocular solution injected transzonularly into the vitreous with the topical formulation of Pred-Moxi-Ketor (given for the first week postoperatively) followed by Pred-Ketor (given for weeks 2–4 after surgery). Patients and methods This was a single-site, single-surgeon, prospective, randomized, subject-masked contralateral eye study with an active comparator and was approved by an appropriate ethics committee. Twenty-five subjects with uncomplicated cataract who were scheduled for cataract surgery were enrolled. If surgery was uneventful, subjects received either an injection in that eye or followed a minimum drop postoperative pharmaceutical regimen. The second eye surgery was performed with the opposite treatment. Subjects were followed for 1 month. Measures of interest were the changes in intraocular pressure (IOP) from baseline and the changes in corneal and macular thickness. Subjects were also asked to evaluate pain perception, visual quality, and overall satisfaction with surgery. They were also asked which regimen they preferred. Results IOP was not statistically significantly different between the groups (P=0.81); there was also no statistically significant difference in IOP over time (P=0.74). There was no statistically significant difference in central macular thickness at 1 week and 1 month between the groups (P=0.18). The central corneal thickness was significantly greater 1 day postoperatively relative to baseline, but there was no statistically significant difference between the groups at any time point (P=0.92). The difference in reported pain was also not statistically significantly different between the groups (P=0.67). Satisfaction with surgery was similar for both groups, but significantly more subjects preferred the injection for overall experience (P<0.01). Conclusion Cataract surgery completed with the two pharmaceutical regimens was similar in outcome. Significantly more

  13. Steroid withdrawal or steroid avoidance in renal transplant recipients: focus on tacrolimus-based immunosuppressive regimens.

    PubMed

    Krämer, B K; Krüger, B; Mack, M; Obed, A; Banas, B; Paczek, L; Schlitt, H J

    2005-05-01

    Steroid-induced adverse effects after transplantation include cosmetic, metabolic, and cardiovascular complications. Steroid withdrawal or avoidance with cyclosporine-based regimens have been hampered by an unacceptably high rate of acute rejections and increased rates of graft loss. Recently the results of several large, randomized trials of steroid withdrawal/avoidance with tacrolimus-based immunosuppression in renal transplant recipients became available. A review of these trials appeared to be of clinical interest. Data from the THOMAS trial clearly indicate that steroid withdrawal from a regimen of tacrolimus, mycophenolate mofetil (MMF), steroids after 3 months after transplantation is safe with regard to acute rejection rate and graft survival. If an induction therapy with daclizumab is used in combination with tacrolimus and MMF (CARMEN trial), even steroid avoidance is safe with regard to acute rejection rate and graft survival. Finally, in the ATLAS trial, steroid avoidance with basiliximab in combination with tacrolimus (resulting in tacrolimus monotherapy) or alternatively with tacrolimus and MMF both resulted in similar graft survival, but higher rates of acute rejection. In conclusion, steroid withdrawal is safe from a triple-drug regimen of tacrolimus, MMF, and steroids after 3 months after transplantation, and steroid use may completely be avoided with tacrolimus, and MMF combined with daclizumab induction. Tacrolimus monotherapy may be achieved using basiliximab induction at the price of higher rates of acute rejection, but with unaffected graft survival. Thus tacrolimus-based immunosuppression with or without interleukin-2 receptor antagonist induction has made steroid withdrawal or avoidance a realistic option in renal transplantation.

  14. Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne Natural History Study

    PubMed Central

    Bello, Luca; Gordish-Dressman, Heather; Morgenroth, Lauren P.; Henricson, Erik K.; Duong, Tina; Hoffman, Eric P.; Cnaan, Avital

    2015-01-01

    Objective: We aimed to perform an observational study of age at loss of independent ambulation (LoA) and side-effect profiles associated with different glucocorticoid corticosteroid (GC) regimens in Duchenne muscular dystrophy (DMD). Methods: We studied 340 participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS). LoA was defined as continuous wheelchair use. Effects of prednisone or prednisolone (PRED)/deflazacort (DFZ), administration frequency, and dose were analyzed by time-varying Cox regression. Side-effect frequencies were compared using χ2 test. Results: Participants treated ≥1 year while ambulatory (n = 252/340) showed a 3-year median delay in LoA (p < 0.001). Fourteen different regimens were observed. Nondaily treatment was common for PRED (37%) and rare for DFZ (3%). DFZ was associated with later LoA than PRED (hazard ratio 0.294 ± 0.053 vs 0.490 ± 0.08, p = 0.003; 2-year difference in median LoA with daily administration, p < 0.001). Average dose was lower for daily PRED (0.56 mg/kg/d, 75% of recommended) than daily DFZ (0.75 mg/kg/d, 83% of recommended, p < 0.001). DFZ showed higher frequencies of growth delay (p < 0.001), cushingoid appearance (p = 0.002), and cataracts (p < 0.001), but not weight gain. Conclusions: Use of DFZ was associated with later LoA and increased frequency of side effects. Differences in standards of care and dosing complicate interpretation of this finding, but stratification by PRED/DFZ might be considered in clinical trials. This study emphasizes the necessity of a randomized, blinded trial of GC regimens in DMD. Classification of evidence: This study provides Class IV evidence that GCs are effective in delaying LoA in patients with DMD. PMID:26311750

  15. Tuberculosis--advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.

    PubMed

    Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin

    2016-04-01

    Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480,000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to

  16. In vivo biofilm formation on stainless steel bonded retainers during different oral health-care regimens

    PubMed Central

    Jongsma, Marije A; van der Mei, Henny C; Atema-Smit, Jelly; Busscher, Henk J; Ren, Yijin

    2015-01-01

    Retention wires permanently bonded to the anterior teeth are used after orthodontic treatment to prevent the teeth from relapsing to pre-treatment positions. A disadvantage of bonded retainers is biofilm accumulation on the wires, which produces a higher incidence of gingival recession, increased pocket depth and bleeding on probing. This study compares in vivo biofilm formation on single-strand and multi-strand retention wires with different oral health-care regimens. Two-centimetre wires were placed in brackets that were bonded to the buccal side of the first molars and second premolars in the upper arches of 22 volunteers. Volunteers used a selected toothpaste with or without the additional use of a mouthrinse containing essential oils. Brushing was performed manually. Regimens were maintained for 1 week, after which the wires were removed and the oral biofilm was collected to quantify the number of organisms and their viability, determine the microbial composition and visualize the bacteria by electron microscopy. A 6-week washout period was employed between regimens. Biofilm formation was reduced on single-strand wires compared with multi-strand wires; bacteria were observed to adhere between the strands. The use of antibacterial toothpastes marginally reduced the amount of biofilm on both wire types, but significantly reduced the viability of the biofilm organisms. Additional use of the mouthrinse did not result in significant changes in biofilm amount or viability. However, major shifts in biofilm composition were induced by combining a stannous fluoride- or triclosan-containing toothpaste with the mouthrinse. These shifts can be tentatively attributed to small changes in bacterial cell surface hydrophobicity after the adsorption of the toothpaste components, which stimulate bacterial adhesion to the hydrophobic oil, as illustrated for a Streptococcus mutans strain. PMID:25572920

  17. Induction of erythroid differentiadon in K562 cells by different butyrate regimens.

    PubMed

    Liu, Zhi-Jie; Qian, Xin-Hua; Li, Xi-Ping; Yao, Ying-Min

    2001-01-01

    OBJECTIVE: To investigate the hemoglobinization induced by butyrate and observe the effects of different butyrate regimens on erythroid differentiation of K562 cells. METHODS: K562 cells, used as an in vitro model system, were stained with benzidine to assess hemoglobin (Hb) production in response to different treatment regimens of butyrate at varied concentrations. Comparison of the percentage of benzidine-positive cells (BZ%)in untreated and butyrate-treated K562 cells was performed. Protein absorption at 414 nm using a spectrophotometer and cellulose acetate gel electrophoresis were employed to determine the changes of Hb production in K562 cells. RESULT: The BZ% increased by 4 to 6 fold and Hb production by 9 to 14 fold 3 d after the cells were incubated with butyrate which selectively promoted fetal hemoglobin(HbF) production in K562 cells. The BZ% increased gradually and reached the peak of l9% to 28% on day 3 or 4 in cells receiving pulse treatment with butyrate for only once, followed by a subsequent rapid fall and on day 7 to 9, it decreased to the level of untreated K562 cells. The length of time for incubation with butyrate was not related to in the increment or the maintenance of the increased level of BZ%. Continuous treatment with butyrate yielded a similar result to that of a single administration of pulse treatment. In contrast, in cells with intermittent pulse treatment the BZ% reached a peak after 72 h and was maintained between 20% and 30% till 3 cycles of treatment was completed. CONCLUSION: Butyrate can induce the expression of globin genes and augment Hb producfion especially that of HbF. A sustained erythroid differentiation of K562 cells can be achieved by intermittent pulse treatment with butyrate which can be an ideal regimen for children with beta globin diseases.

  18. Impact of a Low-Glucose Peritoneal Dialysis Regimen on Fibrosis and Inflammation Biomarkers

    PubMed Central

    Yung, Susan; Lui, Sing Leung; Ng, Chris K.F.; Yim, Andrew; Ma, Maggie K.M.; Lo, Kin Yee; Chow, Chik Cheung; Chu, Kwok Hong; Chak, Wai Leung; Lam, Man Fai; Yung, Chun Yu; Yip, Terence P.S.; Wong, Sunny; Tang, Colin S.O.; Ng, Flora S.K.; Chan, Tak Mao

    2015-01-01

    ♦ Background: The impact of a low-glucose peritoneal dialysis (PD) regimen on biomarkers of peritoneal inflammation, fibrosis and membrane integrity remains to be investigated. ♦ Methods: In a randomized, prospective study, 80 incident PD patients received either a low-glucose regimen comprising Physioneal (P), Extraneal (E) and Nutrineal (N) (Baxter Healthcare Corporation, Deerfield, IL, USA) (PEN group), or Dianeal (control group) for 12 months, after which both groups continued with Dianeal dialysis for 6 months. Serum and dialysate levels of vascular endothelial growth factor (VEGF), decorin, hepatocyte growth factor (HGF), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), hyaluronan (HA), adiponectin, soluble-intracellular adhesion molecule (s-ICAM), vascular cell adhesion molecule-1 (VCAM-1) and P-selectin, and dialysate cancer antigen 125 (CA125), were measured after 12 and 18 months. This paper focuses on results after 12 months, when patients in the PEN group changed to glucose-based PD fluid (PDF). ♦ Results: At the end of 12 months, effluent dialysate levels of CA125, decorin, HGF, IL-6, adiponectin and adhesion molecules were significantly higher in the PEN group compared to controls, but all decreased after patients switched to glucose-based PDF. Macrophage migration inhibitory factor level was lower in the PEN group but increased after changing to glucose-based PDF and was similar to controls at 18 months. Serum adiponectin level was higher in the PEN group at 12 months, but was similar in the 2 groups at 18 months. Body weight, residual renal function, ultrafiltration volume and total Kt/V did not differ between both groups. Dialysate-to-plasma creatinine ratio at 4 h was higher in the PEN group at 12 months and remained so after switching to glucose-based PDF. ♦ Conclusion: Changes in the biomarkers suggest that the PEN PD regimen may be associated with better preservation of peritoneal membrane integrity and reduced

  19. Outcome of a glucocorticoid discontinuation regimen in patients with inactive systemic sclerosis.

    PubMed

    Iudici, Michele; Vettori, Serena; Russo, Barbara; Giacco, Veronica; Capocotta, Domenico; Valentini, Gabriele

    2016-08-01

    Glucocorticoids (GC) are widely used to treat systemic sclerosis (SSc). The lack of efficacy data and patient/physician concerns may prompt therapy discontinuation. The aim of this study is to identify factors hampering GC discontinuation in patients with stable disease on oral GC for longer than 12 months. Consecutive patients fulfilling the 2013 ACR/EULAR criteria for SSc and with stable disease were prescribed a slow tapering GC regimen to achieve discontinuation. At study entry and 6 months later (T6), patients were assessed for disease activity and severity. Moreover, the Short-Form-36; the Health Assessment Questionnaire Disability Index (HAQ-DI); and visual analog scales for fatigue, pain, and general health were completed. Reasons for stopping the discontinuation regimen were recorded. Forty-eight patients (46 females, 9 diffuse SSc), with a mean ± SD age of 56±14 years and a median disease duration of 10 years (range 2-22), were enrolled. The median daily GC dose was 5 mg (range 5-10; all patients treated with prednisone). At T6, 33 (68.7 %) patients had discontinued GC. The remaining 15 patients could not discontinue GC because of arthralgia in eight, arthritis in two, puffy fingers in two, increased creatine-kinase in two, and bursitis in one patient. At multiple logistic analysis, a higher baseline HAQ-DI was the only independent factor associated with GC need (OR 2.98, 95 % CI 1.20-7.41; p = 0.01). About one third of SSc patients did not achieve a GC-free regimen. Disability as assessed by HAQ-DI was the leading factor hindering GC discontinuation. A low HAQ-DI score can identify candidates for GC discontinuation.

  20. Better health-related quality of life after switching from a virologically effective regimen to a regimen containing efavirenz or nevirapine.

    PubMed

    Potard, Valerie; Chassany, Olivier; Lavignon, Marc; Costagliola, Dominique; Spire, Bruno

    2010-01-01

    Switching antiretroviral therapy has been shown as safe and effective, but its impact on health-related quality of life (HRQL) was rarely measured. Our objective was to assess changes in HRQL after switching to an non-nucleoside reverse transcriptase inhibitors (NNRTI) containing regimen among NNRTI-naive HIV-infected patients with viral load (VL) <500 copies/mL. In this prospective observational study, the Hospital Anxiety and Depression, Symptoms checklist, specific World Health Organization Quality of Life (WHOQoL) and generic SF-12v2 HRQL questionnaires were used to assess anxiety, depression, symptoms, and HRQL at baseline and months 1 (M1), 6 (M6), and 12 (M12). The statistical significance of changes in the frequency of anxiety and depression was determined with the McNemar test. Mean changes in the number of symptoms and in HRQL scores were compared using Wilcoxon's paired test. Data were available for 239 patients at baseline (162 with a switch to nevirapine) and for 164 patients at M6. The median age of the patients was 42 years and 67% of patients were male. The proportion of anxious patients diminished at M6 (11%, P=0.02) but not yet at M1. There was no change in the frequency of depression. Significant reductions (p<0.01) were observed at M6 in the mean number of all symptoms (-3.3), lipodystrophy symptoms (-0.8), other symptoms (-2.5), bothersome symptoms (-1.7), bothersome lipodystrophy symptoms (-0.4), and bothersome other symptoms (-1.3). HRQL as assessed with WHOQoL, improved in the physical, independence, and spirituality domains, with a small effect sizes at M6. Both for symptoms and HRQL, these changes were already significant at M1 and persisted at M12. This study shows that in patients with controlled VL, switching to an NNRTI regimen was associated with less anxiety, fewer perceived symptoms, and a small improvement in HRQL, while maintaining virological suppression.

  1. Three-day regimen of oseltamivir for postexposure prophylaxis of influenza in wards.

    PubMed

    Ishiguro, N; Oyamada, R; Nasuhara, Y; Yamada, T; Miyamoto, T; Imai, S; Akizawa, K; Fukumoto, T; Iwasaki, S; Iijima, H; Ono, K

    2016-10-01

    Inpatients who had been in close contact with patients with influenza were given oseltamivir [75mg capsules once daily for adults or 2mg/kg (maximum of 75mg) once daily for children] for three days as postexposure prophylaxis (PEP). The index patients with influenza were prescribed a neuraminidase inhibitor and were discharged immediately or transferred to isolation rooms. The protective efficacy of oseltamivir for three days was 93% overall [95% confidence interval (CI) 53-99%; P=0.023] and 94% for influenza A (95% CI 61-99%; P=0.017), which is comparable to that of seven- to 10-day regimens of oseltamivir as PEP.

  2. Hepatitis C treatment in the elderly: New possibilities and controversies towards interferon-free regimens.

    PubMed

    Vespasiani-Gentilucci, Umberto; Galati, Giovanni; Gallo, Paolo; De Vincentis, Antonio; Riva, Elisabetta; Picardi, Antonio

    2015-06-28

    Due to the progressive aging of the hepatitis C virus (HCV) population which have acquired the infection during its maximum spread after the Second World War, the management of the elderly HCV-infected patient is emerging as a hot topic. Unfortunately, although it is recognized that the progression of HCV-related liver disease gets faster with aging, and that even extra-hepatic manifestations of HCV infection are probably worse in the elderly, till now, treatment attempts in this population have been significantly limited by the well-known contraindications and side effects of interferon (IFN). The arrival of several new anti-HCV drugs, and the possibility to combine them in safe and effective anti-viral regimens, is relighting the hope of a cure for many elderly patients who had been cut out of IFN-based treatments. However, although these new regimens will be certainly more manageable, it should be underscored that IFN-free doesn't mean free from any contraindication or side-effect. Moreover, one issue which promises to become central is that of the possible interactions between antiviral therapy and the multiple drugs frequently assumed by elderly patients because of comorbidities. In this review, we will revise the epidemiology pointing to HCV as an infection of the elderly, the evidences that HCV harms the health of the aged patient more than that of the young one, and the available experiences of HCV treatment in the elderly with the "old" IFN-based regimens and with the newer drugs. We will conclude that the availability of IFN-free regimens should prompt us to change our mind and consider a significantly larger number of possible candidates among elderly patients, who would take significant advantage from viral eradication. Rather than the anagraphic age, drug-drug interactions and, mainly in case of economic restrictions, an evaluation of life expectancy dependent on liver disease with respect to that dependent on comorbidities, are likely to be the key

  3. Combination Regimens of Radiation Therapy and Therapeutic Cancer Vaccines: Mechanisms and Opportunities

    PubMed Central

    Garnett-Benson, Charlie; Hodge, James W.; Gameiro, Sofia R.

    2014-01-01

    Radiation therapy is widely used with curative or palliative intent in the clinical management of multiple cancers. Although mainly aimed at direct tumor cell killing, mounting evidence suggests that radiation can alter the tumor to become an immunostimulatory milieu. Data suggest that the immunogenic effects of radiation can be exploited to promote synergistic antitumor effects in combination with immunotherapeutic agents. Here we review concepts associated with the immunogenic consequences of radiation therapy, and highlight how preclinical findings are translating into clinical benefit for patients receiving combination regimens of radiation therapy and therapeutic cancer vaccines. PMID:25481266

  4. Low-dose allopurinol plus azathioprine/cyclosporin/prednisolone, a novel immunosuppressive regimen.

    PubMed

    Chocair, P; Duley, J; Simmonds, H A; Cameron, J S; Ianhez, L; Arap, S; Sabbaga, E

    1993-07-10

    Early rejection can still complicate renal transplantation even with cyclosporin. We added low-dose allopurinol (25 mg on alternative days) to "triple" immunosuppression with cyclosporin, prednisolone, and azathioprine for twelve recipients of cadaver renal grafts. The controls were fifteen patients on triple therapy alone. Only one rejection episode occurred among the allopurinol-treated patients, whereas eleven controls had rejections (seven with more than one episode). Allopurinol may be toxic when combined with azathioprine, yet the bone marrow tolerated the new regimen well. As expected, reduction of the azathioprine dose was necessary in the treated group.

  5. Enoxaparin can be used safely in patients with severe thrombocytopenia due to intensive chemotherapy regimens.

    PubMed

    Herishanu, Yair; Misgav, Mudi; Kirgner, Ilya; Ben-Tal, Ofira; Eldor, Amiram; Naparstek, Ella

    2004-07-01

    Treatment with intensive chemotherapy regimens is frequently complicated by severe thrombocytopenia. During the period of severe thrombocytopenia, anticoagulant treatment is not uncommonly indicated for thromboembolic events or thromboprophylaxis in these patients. We report 10 hematological patients treated with intensive chemotherapy protocols that were anticoagulated with enoxaparin for catheter related central venous thrombosis and thromboprophylaxis. During the period of severe thrombocytopenia the dosages of enoxaparin were reduced and no major bleeding occurred. Based on our experience we suggest that reduced dosages of low molecular weight heparins may be used relatively safely during transient severe thrombocytopenia.

  6. Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA (``Ecstasy'')

    NASA Astrophysics Data System (ADS)

    Ricaurte, George A.; Yuan, Jie; Hatzidimitriou, George; Cord, Branden J.; McCann, Una D.

    2002-09-01

    The prevailing view is that the popular recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, or ``ecstasy'') is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic neurotoxicity. MDMA neurotoxicity was associated with increased vulnerability to motor dysfunction secondary to dopamine depletion. These results have implications for mechanisms of MDMA neurotoxicity and suggest that recreational MDMA users may unwittingly be putting themselves at risk, either as young adults or later in life, for developing neuropsychiatric disorders related to brain dopamine and/or serotonin deficiency.

  7. Equivalent normalized total dose estimates in cyberknife radiotherapy dose delivery in prostate cancer hypofractionation regimens.

    PubMed

    Sudahar, H; Kurup, P G G; Murali, V; Mahadev, P; Velmurugan, J

    2012-04-01

    As the α/β value of prostate is very small and lower than the surrounding critical organs, hypofractionated radiotherapy became a vital mode of treatment of prostate cancer. Cyberknife (Accuray Inc., Sunnyvale, CA, USA) treatment for localized prostate cancer is performed in hypofractionated dose regimen alone. Effective dose escalation in the hypofractionated regimen can be estimated if the corresponding conventional 2 Gy per fraction equivalent normalized total dose (NTD) distribution is known. The present study aims to analyze the hypofractionated dose distribution of localized prostate cancer in terms of equivalent NTD. Randomly selected 12 localized prostate cases treated in cyberknife with a dose regimen of 36.25 Gy in 5 fractions were considered. The 2 Gy per fraction equivalent NTDs were calculated using the formula derived from the linear quadratic (LQ) model. Dose distributions were analyzed with the corresponding NTDs. The conformity index for the prescribed target dose of 36.25 Gy equivalent to the NTD dose of 90.63 Gy (α/β = 1.5) or 74.31 Gy (α/β = 3) was ranging between 1.15 and 1.73 with a mean value of 1.32 ± 0.15. The D5% of the target was 111.41 ± 8.66 Gy for α/β = 1.5 and 90.15 ± 6.57 Gy for α/β = 3. Similarly, the D95% was 91.98 ± 3.77 Gy for α/β = 1.5 and 75.35 ± 2.88 Gy for α/β = 3. The mean values of bladder and rectal volume receiving the prescribed dose of 36.25 Gy were 0.83 cm3 and 0.086 cm3, respectively. NTD dose analysis shows an escalated dose distribution within the target for low α/β (1.5 Gy) with reasonable sparing of organs at risk. However, the higher α/β of prostate (3 Gy) is not encouraging the fact of dose escalation in cyberknife hypofractionated dose regimen of localized prostate cancer.

  8. Hepatitis C treatment in the elderly: New possibilities and controversies towards interferon-free regimens

    PubMed Central

    Vespasiani-Gentilucci, Umberto; Galati, Giovanni; Gallo, Paolo; De Vincentis, Antonio; Riva, Elisabetta; Picardi, Antonio

    2015-01-01

    Due to the progressive aging of the hepatitis C virus (HCV) population which have acquired the infection during its maximum spread after the Second World War, the management of the elderly HCV-infected patient is emerging as a hot topic. Unfortunately, although it is recognized that the progression of HCV-related liver disease gets faster with aging, and that even extra-hepatic manifestations of HCV infection are probably worse in the elderly, till now, treatment attempts in this population have been significantly limited by the well-known contraindications and side effects of interferon (IFN). The arrival of several new anti-HCV drugs, and the possibility to combine them in safe and effective anti-viral regimens, is relighting the hope of a cure for many elderly patients who had been cut out of IFN-based treatments. However, although these new regimens will be certainly more manageable, it should be underscored that IFN-free doesn’t mean free from any contraindication or side-effect. Moreover, one issue which promises to become central is that of the possible interactions between antiviral therapy and the multiple drugs frequently assumed by elderly patients because of comorbidities. In this review, we will revise the epidemiology pointing to HCV as an infection of the elderly, the evidences that HCV harms the health of the aged patient more than that of the young one, and the available experiences of HCV treatment in the elderly with the “old” IFN-based regimens and with the newer drugs. We will conclude that the availability of IFN-free regimens should prompt us to change our mind and consider a significantly larger number of possible candidates among elderly patients, who would take significant advantage from viral eradication. Rather than the anagraphic age, drug-drug interactions and, mainly in case of economic restrictions, an evaluation of life expectancy dependent on liver disease with respect to that dependent on comorbidities, are likely to be the

  9. A randomized, controlled comparative study of the wrinkle reduction benefits of a cosmetic niacinamide/peptide/retinyl propionate product regimen vs. a prescription 0·02% tretinoin product regimen

    PubMed Central

    Fu, JJJ; Hillebrand, GG; Raleigh, P; Li, J; Marmor, MJ; Bertucci, V; Grimes, PE; Mandy, SH; Perez, MI; Weinkle, SH; Kaczvinsky, JR

    2010-01-01

    Background Tretinoin is considered the benchmark prescription topical therapy for improving fine facial wrinkles, but skin tolerance issues can affect patient compliance. In contrast, cosmetic antiwrinkle products are well tolerated but are generally presumed to be less efficacious than tretinoin. Objectives To compare the efficacy of a cosmetic moisturizer regimen vs. a prescription regimen with 0·02% tretinoin for improving the appearance of facial wrinkles. Methods An 8-week, randomized, parallel-group study was conducted in 196 women with moderate to moderately severe periorbital wrinkles. Following 2 weeks washout, subjects on the cosmetic regimen (n=99) used a sun protection factor (SPF) 30 moisturizing lotion containing 5% niacinamide, peptides and antioxidants, a moisturizing cream containing niacinamide and peptides, and a targeted wrinkle product containing niacinamide, peptides and 0·3% retinyl propionate. Subjects on the prescription regimen (n=97) used 0·02% tretinoin plus moisturizing SPF 30 sunscreen. Subject cohorts (n=25) continued treatment for an additional 16 weeks. Changes in facial wrinkling were assessed by both expert grading and image analysis of digital images of subjects’ faces and by self-assessment questionnaire. Product tolerance was assessed via clinical erythema and dryness grading, subject self-assessment, and determinations of skin barrier integrity (transepidermal water loss) and stratum corneum protein changes. Results The cosmetic regimen significantly improved wrinkle appearance after 8 weeks relative to tretinoin, with comparable benefits after 24 weeks. The cosmetic regimen was significantly better tolerated than tretinoin through 8 weeks by all measures. Conclusions An appropriately designed cosmetic regimen can improve facial wrinkle appearance comparably with the benchmark prescription treatment, with improved tolerability. PMID:20374604

  10. Obese mice on a high-fat alternate-day fasting regimen lose weight and improve glucose tolerance.

    PubMed

    Joslin, P M N; Bell, R K; Swoap, S J

    2016-06-08

    Alternate-day fasting (ADF) causes body weight (BW) loss in humans and rodents. However, it is not clear that ADF while maintaining a high-fat (HF) diet results in weight loss and the accompanying improvement in control of circulating glucose. We tested the hypotheses that a high-fat ADF protocol in obese mice would result in (i) BW loss, (ii) improved glucose control, (iii) fluctuating phenotypes on 'fasted' days when compared to 'fed' days and (iv) induction of torpor on 'fasted days'. We evaluated the physiological effects of ADF in diet-induced obese mice for BW, heart rate (HR), body temperature (Tb ), glucose tolerance, insulin responsiveness, blood parameters (leptin, insulin, free fatty acids) and hepatic gene expression. Diet-induced obese male C57BL/6J mice lost one-third of their pre-diet BW while on an ADF diet for 10 weeks consisting of HF food. The ADF protocol improved glucose tolerance and insulin sensitivity, although mice on a fast day were less glucose tolerant than the same mice on a fed day. ADF mice on a fast day had low circulating insulin, but had an enhanced response to an insulin-assisted glucose tolerance test, suggesting the impaired glucose tolerance may be a result of insufficient insulin production. On fed days, ADF mice were the warmest, had a high HR and displayed hepatic gene expression and circulating leptin that closely mimicked that of mice fed an ad lib HF diet. ADF mice never entered torpor as assessed by HR and Tb . However, on fast days, they were the coolest, had the slowest HR, and displayed hepatic gene expression and circulating leptin that closely mimicked that of Chow-Fed mice. Collectively, the ADF regimen with a HF diet in obese mice results in weight loss, improved blood glucose control, and daily fluctuations in selected physiological and biochemical parameters in the mouse.

  11. Nursing regimens: effects on body condition, return to postpartum ovarian cyclicity in Santa Ines ewes, and performance of lambs.

    PubMed

    Ascari, I J; Alves, A C; Pérez, J R O; Lima, R R; Garcia, I F F; Nogueira, G P; Junqueira, F B; Castro, T R; Aziani, W L B; Alves, N G

    2013-08-01

    The effects of nursing regimens on the body condition, onset of ovarian cyclicity postpartum and weaning weight of lambs were assessed in Santa Ines ewes. Thirty-two ewes were blocked according to parity, number of lambs, and body weight at lambing and within each block randomly allocated to treatments: continuous nursing (CN), controlled nursing (CN2) with two daily feedings for an hour after the 10th day postpartum, or early weaning (EW) with total separation from the lambs after the 10th day. The animals were evaluated from the 12th day postpartum until the first estrus or until 60th day. The dry matter and nutrients intake did not differ among treatments (P>0.05) but did differ over time (P<0.01). The weight, body condition score, serum concentrations of non-esterified fatty acids and prolactin, the percentages of ewes in estrus, of ewes that ovulated within 60th day and had ovulation silent, the period from lambing to estrus, ovulation and follicle with a diameter ≥5mm and the maximum follicular diameter did not differ (P>0.05) among the treatments. The percentage of ovulation until 30th day was greater (P<0.05) in the EW group. The percentage of short luteal phases was higher in the CN2 and EW groups (P=0.07) and normal luteal phases were higher in the CN group (P=0.01). Lamb weight weaning was lower in the EW group (P<0.05). It is possible to use CN to obtain lambing periods less than eight months in Santa Ines ewes, with the advantages of simpler management and higher lamb weaning weights.

  12. (The role of zooplankton in the cycling and remineralization of chemical materials in the Southern California Bight): California Basin Study: DOE west coast basin program: Progress report 4, (June 1987--June 1988)

    SciTech Connect

    Small, L.F.; Huh, Chih-An

    1988-06-01

    The overall objective of our research, within the structure of the DOE CaBS (California Basin Study) program, is to understand the transport pathways and mass balances of selected metabolically active and inactive chemical species in the Santa Monica/San Pedro Basins. One focus of our study is to examine the role of zooplankton and micronekton in the cycling and remineralization of chemical materials in the Southern California Bight, with particular reference to C, N and certain radionuclides and trace metals. A second focus is to examine these same radionuclides and trace metals in other reservoirs besides the zooplankton (i.e., in seawater, sediment trap material and bottom sediments). Knowledge of the rates, routes and reservoirs of these nuclides and metals should lead to a cogent model for these elements in Santa Monica/San Pedro Basins. Our zooplankton C and N data, in conjunction with primary production, microbiological and sediment flux data from colleagues in the program, should also lead ultimately to a model of C and N cycling in the basins. 33 refs., 13 figs., 7 tabs.

  13. Treatment of Light Chain Deposition Disease Using Bortezomib-Based Regimen Followed by Thalidomide-Based Regimen in a Saudi Male

    PubMed Central

    Al-Ghamdi, Mushabab; Ahmad, Mustafa

    2016-01-01

    Light chain deposition disease (LCDD) is a rare illness with, as yet, no clear evidence-based guidelines for its treatment. To the best of our knowledge, LCDD has not been previously reported from Saudi Arabia. We present in this report, a 38-year-old Saudi male who presented with clinical features suggestive of hypertensive nephropathy but kidney biopsy later revealed the diagnosis of LCDD. His serum creatinine at presentation was 297 μmol/L which came down to 194 μmol/L on treatment with Bortezomib, Cyclophosphamide and Dexamethasone. His 24-hour protein excretion at presentation was 6 g/L which also came down to less than 1 g/day. He was later placed on Cyclophosphamide, Thalidomide, and Dexamethasone regimen because of persistent high titres of serum free light chains. He went into remission with undetectable serum free light chains and remained so for three years at the time of writing this report. We conclude that LCDD, though rare, does occur in Saudi population. The treatment of LCDD is challenging but the use of Bortezomib, a proteosome inhibitor, is promising. However, suboptimal response may require further treatment with other therapeutic options such as chemotherapy with alkylating agents or high-dose Melphalan with autologous stem cell transplant. PMID:28083151

  14. Advanced neuroblastoma: improved response rate using a multiagent regimen (OPEC) including sequential cisplatin and VM-26.

    PubMed

    Shafford, E A; Rogers, D W; Pritchard, J

    1984-07-01

    Forty-two children, all over one year of age, were given vincristine, cyclophosphamide, and sequentially timed cisplatin and VM-26 (OPEC) or OPEC and doxorubicin (OPEC-D) as initial treatment for newly diagnosed stage III or IV neuroblastoma. Good partial response was achieved in 31 patients (74%) overall and in 28 (78%) of 36 patients whose treatment adhered to the chemotherapy protocol, compared with a 65% response rate achieved in a previous series of children treated with pulsed cyclophosphamide and vincristine with or without doxorubicin. Only six patients, including two of the six children whose treatment did not adhere to protocol, failed to respond, but there were five early deaths from treatment-related complications. Tumor response to OPEC, which was the less toxic of the two regimens, was at least as good as tumor response to OPEC-D. Cisplatin-induced morbidity was clinically significant in only one patient and was avoided in others by careful monitoring of glomerular filtration rate and hearing. Other centers should test the efficacy of OPEC or equivalent regimens in the treatment of advanced neuroblastoma.

  15. Audit of multiple insulin injection regimens in a large outpatient diabetic population.

    PubMed

    Gordon, D; Wilson, M; Paterson, K R; Semple, C G

    1992-08-01

    One hundred out-patients treated by multiple insulin injection regimens underwent clinical audit by retrospective analysis of their case-notes. Patients had been on multiple insulin injection therapy (MIIT) for 1.0-4.5 years (median, 3.6 years) and had had diabetes for 2 months-33 years (median, 8.7 years) at the time of starting pen therapy. Median daily insulin dose per patient did not differ significantly following stabilisation on MIIT or at latest follow-up. The median glycated haemoglobin did not change during each of the 4 years of follow-up. During the year prior to commencing MIIT the patients showed no significant alteration in body weight. Patients' weights rose significantly during each subsequent year. Median weight gains were 0.9 kg (P less than 0.005) during the first year, 1.4 kg (P less than 0.005) during the second year, 0.9 kg (P less than 0.05) during the third year and 1.4 kg (P less than 0.05) during year 4. No such weight gain was recorded in a control group of 30 patients matched for age and duration of diabetes and treated by twice daily insulin injections. Multiple insulin injection regimens used over prolonged periods in a routine clinic setting do not alter metabolic control. However, continuing weight gain appears to occur despite similar daily insulin doses.

  16. Combined-modality therapy of rectal cancer with oxaliplatin-based regimens.

    PubMed

    Minsky, Bruce D

    2004-06-01

    There are 2 conventional treatments for clinically resectable rectal cancer. First is surgery and, if the tumor is stage T3 and/or N1/2, this is followed by postoperative combined modality therapy. The second is preoperative combined modality therapy followed by surgery and postoperative combined modality therapy if the tumor is stage uT3/4 and/or node-positive. There are a number of new chemotherapeutic agents that have been developed for the treatment of patients with colorectal cancer. Phase I/II trials examining the use of these new chemotherapeutic agents in combination with pelvic radiation therapy, most commonly in the preoperative setting are in progress and suggest higher complete response rates. There is considerable interest in integrating oxaliplatin into preoperative combined modality therapy regimens for rectal cancer. Based on results from phase I/II trials, the recommended regimen for patients who receive oxaliplatin-based combined modality therapy is continuous infusion 5-fluorouracil or capecitabine with pelvic radiation.

  17. Defining the Diversity of Phenotypic Respecification Using Multiple Cell Lines and Reprogramming Regimens

    PubMed Central

    Alicea, Bradly; Murthy, Shashanka; Keaton, Sarah A.; Cobbett, Peter; Cibelli, Jose B.

    2013-01-01

    To better understand the basis of variation in cellular reprogramming, we performed experiments with two primary objectives: first, to determine the degree of difference, if any, in reprogramming efficiency among cells lines of a similar type after accounting for technical variables, and second, to compare the efficiency of conversion of multiple similar cell lines to two separate reprogramming regimens–induced neurons and induced skeletal muscle. Using two reprogramming regimens, it could be determined whether converted cells are likely derived from a distinct subpopulation that is generally susceptible to reprogramming or are derived from cells with an independent capacity for respecification to a given phenotype. Our results indicated that when technical components of the reprogramming regimen were accounted for, reprogramming efficiency was reproducible within a given primary fibroblast line but varied dramatically between lines. The disparity in reprogramming efficiency between lines was of sufficient magnitude to account for some discrepancies in published results. We also found that the efficiency of conversion to one phenotype was not predictive of reprogramming to the alternate phenotype, suggesting that the capacity for reprogramming does not arise from a specific subpopulation with a generally “weak grip” on cellular identity. Our findings suggest that parallel testing of multiple cell lines from several sources may be needed to accurately assess the efficiency of direct reprogramming procedures, and that testing a larger number of fibroblast lines—even lines with similar origins—is likely the most direct means of improving reprogramming efficiency. PMID:23672680

  18. Therapeutic efficacy of mammary irrigation regimen in dairy cattle diagnosed with acute coliform mastitis.

    PubMed

    Shinozuka, Yasunori; Hirata, Harumi; Ishibashi, Ichiro; Okawa, Yuzo; Kasuga, Asako; Takagi, Mitsuhiro; Taura, Yasuho

    2009-03-01

    The objective of this field study was to determine the therapeutic efficacy of mammary irrigation for the treatment of dairy cattle diagnosed with acute coliform mastitis caused by gram-negative bacteria. Additionally, the effects of different mammary irrigation regimen fluids such as ozone water and normal saline were compared. Dairy cattle clinically diagnosed with acute coliform mastitis (n = 57) were enrolled in the study, randomly assigned to 1 of 3 groups, and received the following treatments: systemic antibiotic administration (SAA group; n = 40), mammary irrigation regimen (MIR group; n = 10), and both treatments (MIX group; n=7). Significant antipyretic effects, as assessed by rectal temperature measurement, were observed in the MIX and MIR groups. Although 2 irrigating fluids were used, namely, ozone water and normal saline, no significant difference was observed between the 2 groups. Fourteen days after the onset of the treatments, the milk yield recovery rate in MIR group tended to be higher (p = 0.06) than that in the SAA group. Additionally, after 30 days of treatment, the MIR group cows demonstrated significantly higher successful recovery rates (p<0.05) than the SAA group cows. These results indicate that mammary irrigation with normal saline is an effective treatment for acute coliform mastitis in dairy cattle.

  19. The use of a computer-assisted rehabilitation environment (CAREN) for enhancing wounded warrior rehabilitation regimens

    PubMed Central

    Isaacson, Brad M.; Swanson, Thomas M.; Pasquina, Paul F.

    2013-01-01

    Purpose This paper seeks to describe how novel technologies such as the computer-assisted research environment (CAREN) may improve physical and cognitive rehabilitation for wounded warfighters. Design/methodology/approach The CAREN system is a dynamic platform which may assist service members who have sustained improvised explosive device injuries during Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn. The complex nature of warfighter injuries present unique rehabilitation challenges that demand new tools for quick return to active duty or the civilian community. Findings Virtual reality-based gait training programs may directly influence physiological and biomechanical performance for those who have endured combat injuries. The CAREN system provides a safe, interactive environment for the user while capturing kinematic and kinetic data capture to improve rehabilitation regimens. Conclusions This paper provides an overview of the CAREN system and describes how this dynamic rehabilitation aid may be a translational tool for collecting biomechanical and physiological data during prosthetic training. The CAREN platform allows users to be fully immersed in a virtual environment while healthcare providers use these simulations to improve gait and stability, obstacle avoidance, or improved weight shifting. As such, rehabilitation regimens may be patient specific. PMID:23820145

  20. Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms.

    PubMed

    Yang, Shoufeng; Hay, Iain D; Cameron, David R; Speir, Mary; Cui, Bintao; Su, Feifei; Peleg, Anton Y; Lithgow, Trevor; Deighton, Margaret A; Qu, Yue

    2015-12-21

    Biofilm formation is a major pathogenicity strategy of Staphylococcus epidermidis causing various medical-device infections. Persister cells have been implicated in treatment failure of such infections. We sought to profile bacterial subpopulations residing in S. epidermidis biofilms, and to establish persister-targeting treatment strategies to eradicate biofilms. Population analysis was performed by challenging single biofilm cells with antibiotics at increasing concentrations ranging from planktonic minimum bactericidal concentrations (MBCs) to biofilm MBCs (MBCbiofilm). Two populations of "persister cells" were observed: bacteria that survived antibiotics at MBCbiofilm for 24/48 hours were referred to as dormant cells; those selected with antibiotics at 8 X MICs for 3 hours (excluding dormant cells) were defined as tolerant-but-killable (TBK) cells. Antibiotic regimens targeting dormant cells were tested in vitro for their efficacies in eradicating persister cells and intact biofilms. This study confirmed that there are at least three subpopulations within a S. epidermidis biofilm: normal cells, dormant cells, and TBK cells. Biofilms comprise more TBK cells and dormant cells than their log-planktonic counterparts. Using antibiotic regimens targeting dormant cells, i.e. effective antibiotics at MBCbiofilm for an extended period, might eradicate S. epidermidis biofilms. Potential uses for this strategy are in antibiotic lock techniques and inhaled aerosolized antibiotics.

  1. Single Tablet Regimen Usage and Efficacy in the Treatment of HIV Infection in Australia.

    PubMed

    Armstrong, B; Chan, D J; Stewart, M J; Fagan, D; Smith, D

    2015-01-01

    Single tablet regimens (STRs) for HIV infection improve patient satisfaction, quality of life, medication adherence, and virological suppression compared to multitablet regimens (MTRs). This is the first study assessing STR uptake and durability in Australia. This retrospective audit of all patients receiving an STR (n = 299) at a large Sydney HIV clinic (January 2012-December 2013) assessed patient demographics, treatment prior to STR, HIV RNA load and CD4 during MTR and STR dosing, and reasons for STR switch. 206 patients switched from previous antiretroviral treatment to an STR, of which 88% switched from an MTR. Reasons for switching included desire to simplify treatment (57%), reduced side effects or toxicity (18%), and cost-saving for the patient. There was no switching for virological failure. Compared to when on an MTR, patients switching to an STR had significantly lower HIV RNA counts (p < 0.001) and significantly higher CD4 counts (p < 0.001). The discontinuation rate from STR was very low and all patients who switched to an STR maintained virological suppression throughout the study duration, although the study is limited by the absence of a control group.

  2. Which long-term antiplatelet regimen for patients with acute coronary syndromes?

    PubMed

    Picchi, Andrea; Ferlini, Marco; Limbruno, Ugo; De Servi, Stefano

    2016-06-01

    Dual antiplatelet therapy (DAPT ) is recommended up to 12 months in patients with acute coronary syndromes, but the risk of cardiovascular events in this group of subjects remains high, also in the long-term follow-up. The potential benefit of a prolonged period of DAPT has recently been assessed in three large-volume randomized clinical trials (PEGASUS, DAPT-MI, TRA2P-TIMI 50) but final results are quite difficult to interpret and clear indications for the clinical practice are so far lacking. A direct comparison of the three studies is challenging since relevant differences exist as to clinical features and risk profile of the study populations. Different anti-platelet drugs have been tested in addition to aspirin making it difficult to understand which antithrombotic regimen guarantees the best balance between thrombotic and haemorragic events. Finally, specific designs of these trials, evaluating complex composite end-points, may generate further difficulties in the interpretation of data. We believe that the use of total mortality rather than cardiovascular death as end-point, would better describe the long-term outcome incorporating the catastrophic consequences of bleeding. This review seeks to highlight strengths and weaknesses of these three large-volume trials and tries to establish whether or not prolonging DAPT beyond 12 months in patients with acute coronary syndromes is useful and which anti-thrombotic regimen would offer the best balance between thrombotic and bleeding risk.

  3. Exploring Drug Dosing Regimens In Vitro Using Real-Time 3D Spheroid Tumor Growth Assays.

    PubMed

    Lal-Nag, Madhu; McGee, Lauren; Titus, Steven A; Brimacombe, Kyle; Michael, Sam; Sittampalam, Gurusingham; Ferrer, Marc

    2017-03-01

    Two-dimensional monolayer cell proliferation assays for cancer drug discovery have made the implementation of large-scale screens feasible but only seem to reflect a simplified view that oncogenes or tumor suppressor genes are the genetic drivers of cancer cell proliferation. However, there is now increased evidence that the cellular and physiological context in which these oncogenic events occur play a key role in how they drive tumor growth in vivo and, therefore, in how tumors respond to drug treatments. In vitro 3D spheroid tumor models are being developed to better mimic the physiology of tumors in vivo, in an attempt to improve the predictability and efficiency of drug discovery for the treatment of cancer. Here we describe the establishment of a real-time 3D spheroid growth, 384-well screening assay. The cells used in this study constitutively expressed green fluorescent protein (GFP), which enabled the real-time monitoring of spheroid formation and the effect of chemotherapeutic agents on spheroid size at different time points of sphere growth and drug treatment. This real-time 3D spheroid assay platform represents a first step toward the replication in vitro of drug dosing regimens being investigated in vivo. We hope that further development of this assay platform will allow the investigation of drug dosing regimens, efficacy, and resistance before preclinical and clinical studies.

  4. Evaluation of the benefit of addition of clidinium C to a Helicobacter pylori eradication regimen

    PubMed Central

    Chorami, Maryam; Naderi, Nosratollah; Moghimi-Dehkordi, Bijan; Mirsattari, Dariush; Shalmani, Hamid Mohaghegh

    2013-01-01

    Aim This study aimed to evaluate the success of H.pylori eradication therapy in patients with dyspepsia by therapeutics regimes with and without clidinium C. Background Helicobacter pylori infections are reported in all parts of the world. Appropriate antibiotic therapy can treat infection. The ideal treatment regimen has not been specified. Patients and methods In a randomized, double blind clinical trials study, 250 patients with dyspepsia were enrolled. All patients were treated by Omeprazole, Metronidazole, Amoxicillin and Bismuth (OMAB) for two weeks. One tablet clidinium C before each meal was added to this regimen in the intervention group (A). Urea Breath Test (UBT) was carried out after 8-12 weeks after treatment for evaluation of H.pylori eradication. Results 132 patients in the intervention group (A) and 118 patients in the control group (B) were enrolled to the study. The rate of eradication in group A was significantly higher than group B (62.1% vs. 50%, p=0.04). Conclusion The results supported the effect of clidinium C for increasing of helicobacter pylori eradication, but further studies need to be performed. PMID:24834261

  5. Bactericidal and sterilizing activities of several orally administered combined regimens against Mycobacterium ulcerans in mice.

    PubMed

    Ji, Baohong; Chauffour, Aurélie; Robert, Jérome; Jarlier, Vincent

    2008-06-01

    Treatment with rifampin-clarithromycin or moxifloxacin-clarithromycin for 8 weeks displayed promising bactericidal activity against Mycobacterium ulcerans in mice; none of the mice treated with rifampin-clarithromycin relapsed, whereas 59% of those treated with moxifloxacin-clarithromycin relapsed after treatment was stopped. The bactericidal and sterilizing activities of the five-times-weekly (5/7) administration of 5 mg of rifapentine/kg of body weight, either alone or in combination, were virtually identical to those of the corresponding regimens with 10 mg of rifampin/kg of body weight; however, because of the long half-life of rifapentine, accumulation of the drug after 5/7 administration is a concern. The bactericidal activity of 20 mg/kg rifapentine in monotherapy or 20 mg/kg rifapentine in combination with 150 mg/kg streptomycin or 200 mg/kg moxifloxacin administered twice weekly was as effective as the corresponding regimens containing 10 mg/kg rifampin administered 5/7, suggesting that Buruli ulcer might be treated with intermittently administered rifapentine-containing combinations.

  6. Efficacy of different primaquine-based antimalarial regimens against Plasmodium falciparum gametocytemia.

    PubMed

    Arango, Eliana M; Upegui, Yulieth A; Carmona-Fonseca, Jaime

    2012-05-01

    This study compared the efficacy against Plasmodium falciparum gametocytes of four regimens: amodiaquine-sulfadoxine/pyrimethamine (AQ-SP) and mefloquine-artesunate (MQ-AS), with and without primaquine (PQ) administered with the second dose of the schizonticide (AQ-SP; AQ-SP-PQ; MQ-AS; MQ-AS-PQ). Efficacy was determined by thick smear on days 1, 4 and 8 after the beginning of treatment. A total of 82 patients (19-23/group) were recruited. After AQ-SP administration, gametocytemia steadily increased until day 8. With AQ-SP-PQ, a marked decline in gametocytemia was detected on days 4 and 8. MQ-AS treatment resulted in reduced gametocytemia on days 4 and 8, and with MQ-AS-PQ it was reduced even further. None of the treatments cleared gametocytemia by day 8. Currently, artemisinin-based combination therapies plus PQ are the recommended treatment option against falciparum malaria; however, further studies are required to optimize the use of PQ. Issues to be addressed include the optimal time of administration, treatment duration, optimal daily and total dose, and day of evaluation of the gametocytocidal effect. In falciparum malaria, the WHO recommends a maximum of 4days of treatment; consequently, an effective regimen must clear asexual parasites and symptoms within this time frame. The same criteria should be taken into account when evaluating the anti-gametocyte activity.

  7. Hepatitis B Vaccination in HIV-Infected Youth: A Randomized Trial of Three Regimens

    PubMed Central

    Flynn, Patricia M.; Cunningham, Coleen K.; Rudy, Bret; Wilson, Craig M.; Kapogiannis, Bill; Worrell, Carol; Bethel, James; Monte, Dina; Bojan, Kelly

    2011-01-01

    Background HIV-infected youth are at risk of hepatitis B (HBV) infection and should be vaccinated. Previous reports suggest reduced response to standard HBV vaccine regimens. Methods HIV-infected youth, age 12 to <25 years, were randomly assigned to one of three treatment arms: Arm 1: Engerix B®, 20 mcg HBsAg; Arm 2: Engerix B®, 40 mcg; and Arm 3: Twinrix®, 20mcg HBsAg combined with 720 ELU hepatitis A antigen. Vaccines were administered at weeks 0, 4 and 24. Results Characteristics of evaluable patients (n=336) at entry were similar in the study arms. At enrollment, median CD4+ T-cell count was 460 cells/mm3 (IQR: 305 to 668); 13% were < 200 cells/mm3. Among Engerix B®, 20 mcg recipients, 60.4% responded to vaccine (HBsAb ≥ 10 IU/mL at week 28). Improved vaccine response was seen in recipients of Engerix B®, 40 mcg, (73.2%, vs. Arm 1, p=0.04) and Twinrix® (75.4%, vs. Arm 1, p=0.02). In multivariate analysis, only baseline CD4+ T-cell count and study arm were independent predictors of vaccine response. Conclusions In HIV-infected youth, a three dose vaccination regimen with Engerix B®, 40 mcg, or Twinrix® and higher baseline CD4+ T-cell counts were independently associated with improved vaccine response. PMID:21350366

  8. Compliance with Xylitol and Sorbitol Chewing Gum Regimens in Clinical Trials

    PubMed Central

    BRETZ, WALTER A.; ROSA, ODILA P. S.; SILVA, SALETE M. B.; CORBY, PATRICIA M. A.; MILANDA, MARCELO; LOESCHE, WALTER J.

    2011-01-01

    Objective The purpose of this study was to investigate compliance of long-term xylitol and sorbitol chewing gum regimens in adult women participating in a double-blind randomized controlled clinical trial. Design The participants included 122 mothers (age range: 16–35 years) residing in the city of Bauru, São Paulo, Brazil. Compliance with the xylitol and sorbitol chewing gum regimens was assessed by weighing, with a precision balance, all used gums returned in zip-lock bags during the study period of 33 months. The total number of returned bags in both chewing gum groups was computed and the differences between groups were determined by one-way ANOVA. Compliance was further categorized into excellent, good, fair or poor based on the distribution of the combined data for both groups by quartiles. These distributions for the xylitol and sorbitol groups were subjected to chi-square analysis. Results Compliance was always superior for the xylitol group in all categories. These distributions were, however, not significantly different in statistical terms. Average compliance in the xylitol chewing gum group was significantly higher when compared to the sorbitol chewing gum group (p=0.0481). Conclusions The results suggest that compliance, and possibly acceptance in this population, was superior for xylitol chewing gum than for sorbitol chewing gum. PMID:22241940

  9. Practical Strategies for Enhancing Adherence to Treatment Regimen in Inflammatory Bowel Disease

    PubMed Central

    Greenley, Rachel N.; Kunz, Jennifer H.; Walter, Jennifer; Hommel, Kevin A.

    2013-01-01

    Promoting adherence to treatment among pediatric and adult patients with inflammatory bowel disease (IBD) is a critical yet challenging task for health care providers. Several existing interventions to enhance adherence among individuals with IBD offer useful information about practical strategies to enhance adherence. The current review article has 3 goals. First, the review provides a context for understanding treatment regimen adherence in IBD by reviewing key definitional, measurement, and conceptual challenges in this area. Next, published studies focused on interventions to enhance adherence in IBD are briefly summarized, followed by a synthesis of practical adherence promotion strategies for use in IBD by health care providers. Strategies are distinguished by the level of evidence supporting their utility as well as by age group. Finally, recommendations for future research to facilitate the development and implementation of practical, evidence-based strategies for adherence promotion in IBD are provided. Findings from the literature review suggest that strategies including education, regimen simplification, and use of reminder systems and organizational strategies (e.g., pill boxes) are likely to be best suited for addressing accidental nonadherence. In contrast, addressing motivational issues, teaching problem-solving skills, and addressing problematic patterns of family functioning are more likely to benefit individuals displaying intentional nonadherence. PMID:23635715

  10. Practical strategies for enhancing adherence to treatment regimen in inflammatory bowel disease.

    PubMed

    Greenley, Rachel N; Kunz, Jennifer H; Walter, Jennifer; Hommel, Kevin A

    2013-06-01

    Promoting adherence to treatment among pediatric and adult patients with inflammatory bowel disease (IBD) is a critical yet challenging task for health care providers. Several existing interventions to enhance adherence among individuals with IBD offer useful information about practical strategies to enhance adherence. The current review article has 3 goals. First, the review provides a context for understanding treatment regimen adherence in IBD by reviewing key definitional, measurement, and conceptual challenges in this area. Next, published studies focused on interventions to enhance adherence in IBD are briefly summarized, followed by a synthesis of practical adherence promotion strategies for use in IBD by health care providers. Strategies are distinguished by the level of evidence supporting their utility as well as by age group. Finally, recommendations for future research to facilitate the development and implementation of practical, evidence-based strategies for adherence promotion in IBD are provided. Findings from the literature review suggest that strategies including education, regimen simplification, and use of reminder systems and organizational strategies (e.g., pill boxes) are likely to be best suited for addressing accidental nonadherence. In contrast, addressing motivational issues, teaching problem-solving skills, and addressing problematic patterns of family functioning are more likely to benefit individuals displaying intentional nonadherence.

  11. NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease

    SciTech Connect

    Hagemeister, F.B.; Cabanillas, F.; Velasquez, W.S.; Meistrich, M.L.; Liang, J.C.; McLaughlin, P.; Redman, J.R.; Romaguera, J.E.; Rodriguez, M.A.; Swan, F. Jr. )

    1990-12-01

    Patients with early-staged Hodgkin's disease have had a higher relapse rate following radiotherapy alone if they have B symptoms, large mediastinal masses, hilar involvement, or stage III disease. From June 1988 to December 1989, 27 previously untreated patients with early-staged Hodgkin's disease with adverse features for disease-free survival received combined-modality therapy. Seventeen patients had stage I or II disease, 10 had stage III, 5 had B symptoms, 13 had large mediastinal masses, and 6 had peripheral masses measuring 10 cm or more in diameter. All patients initially received three cycles of a novel chemotherapeutic regimen combining Novantrone (mitoxantrone, American Cyanamid Company), vincristine, vinblastine, and prednisone (NOVP). Twenty-four patients with clinically staged I or II disease with adverse features or stage III disease did not undergo laparotomy; three patients had favorable stage I or II disease and at laparotomy had stage III disease. Radiotherapy-treatment fields depended on the extent of nodal involvement. Twenty-six patients completed all therapy as planned to complete remission (CR) and one of these has had progression; she is in second CR following additional radiotherapy. With a median follow-up of 12 months, all patients are alive. Tolerance to treatment was excellent with only grade 1 or 2 nausea, alopecia and myalgias, and brief myelosuppression. NOVP is an effective adjuvant chemotherapy regimen for inducing responses, with minimal toxicity, prior to definitive radiotherapy for patients with early-staged Hodgkin's disease.

  12. Gene therapy for HIV/AIDS: the potential for a new therapeutic regimen.

    PubMed

    Fanning, Greg; Amado, Rafael; Symonds, Geoff

    2003-08-01

    Human Immunodeficiency Virus (HIV) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). HIV/AIDS is a disease that, compared with the not so distant past, is now better held in check by current antiretroviral drugs. However, it remains a disease not solved. Highly active antiretroviral therapy (HAART) generally uses two non-nucleoside and one nucleoside reverse transcriptase (RT) inhibitor or two non-nucleoside RT and one protease inhibitor. HAART is far more effective than the mono- or duo-therapy of the past, which used compounds like the nucleoside reverse transcriptase inhibitor AZT or two nucleoside reverse transcriptase inhibitors. However, even with the relatively potent drug cocktails that comprise HAART, there are the issues of (i). HIV escape mutants, (ii). an apparent need to take the drugs in an ongoing manner, and (iii). the drugs' side effects that are often severe. This review speaks to the potential addition to these potent regimens of another regimen, namely the genetic modification of target hematopoietic cells. Such a new treatment paradigm is conceptually attractive as it may yield the constant intracellular expression of an anti-HIV gene that acts to inhibit HIV replication and pathogenicity. A body of preclinical work exists showing the inhibition of HIV replication and decreased HIV pathogenicity by anti-HIV genetic agents. This preclinical work used hematopoietic cell lines and primary cells as the target tissue. More recently, several clinical trials have sought to test this concept in vivo.

  13. Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials

    PubMed Central

    Brown, Scott A.; Surman, Sherri L.; Sealy, Robert; Jones, Bart G.; Slobod, Karen S.; Branum, Kristen; Lockey, Timothy D.; Howlett, Nanna; Freiden, Pamela; Flynn, Patricia; Hurwitz, Julia L.

    2010-01-01

    Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus) and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans. PMID:20407589

  14. Rate of expulsion of Trichuris trichiura with multiple and single dose regimens of albendazole.

    PubMed

    Bundy, D A; Thompson, D E; Cooper, E S; Blanchard, J

    1985-01-01

    The efficacy of multiple and single dose regimens of albendazole on Trichuris trichiura infection was evaluated by counting the number of worms expelled/day from two pair-matched groups of children, for nine days following therapy. The temporal patterns of worm expulsion were similar whether the children received a single 400 mg dose or two consecutive doses: no worms were passed before the second day, or after the sixth day, after intervention, and the maximum worm expulsion rate was attained on the fourth day. A second treatment six days after the first expelled no more worms. The results obtained here resemble those obtained previously with a three-day (600 mg) regimen of mebendazole in a study of heavily infected children. We conclude: that irrespective of dose, benzimidazole carbamates require the gut transit time plus 48 hours to immobilize T. trichiura; and that a single dose of albendazole is effective against light infections of T. trichiura but requires further evaluation with high intensity infections.

  15. Personalized intensification of insulin therapy in type 2 diabetes - does a basal-bolus regimen suit all patients?

    PubMed

    Giugliano, D; Sieradzki, J; Stefanski, A; Gentilella, R

    2016-08-01

    Many patients with type 2 diabetes mellitus (T2DM) require insulin therapy. If basal insulin fails to achieve glycemic control, insulin intensification is one possible treatment intensification strategy. We summarized clinical data from randomized clinical trials designed to compare the efficacy and safety of basal-bolus and premixed insulin intensification regimens. We defined a between-group difference of ≥0.3% in end-of-study glycated hemoglobin (HbA1c) as clinically meaningful. A PubMed database search supplemented by author-identified papers yielded 15 trials which met selection criteria: randomized design, patients with T2DM receiving basal-bolus (bolus injection ≤3 times/day) vs. premixed (≤3 injections/day) insulin regimens, primary/major endpoint(s) HbA1c- and/or hypoglycemia-related, and trial duration ≥12 weeks. Glycemic control improved with both basal-bolus and premixed insulin regimens with - in most cases - acceptable levels of weight gain and hypoglycemia. A clinically meaningful difference between regimens in glycemic control was recorded in only four comparisons, all of which favored basal-bolus therapy. The incidence of hypoglycemia was significantly different between regimens in only three comparisons, one of which favored premixed insulin and two basal-bolus therapy. Of the four trials that reported a significant difference between regimens in bodyweight change, two favored basal-bolus therapy and two favored premixed insulin. Thus, on a population level, neither basal-bolus therapy nor premixed insulin showed a consistent advantage in terms of glycemic control, hypoglycemic risk, or bodyweight gain. It is therefore recommended that clinicians should adopt an individualized approach to insulin intensification - taking into account the benefits and risks of each treatment approach and the attitude and preferences of each patient - in the knowledge that both basal-bolus and premixed regimens may be successful.

  16. Front-loaded linezolid regimens result in increased killing and suppression of the accessory gene regulator system of Staphylococcus aureus.

    PubMed

    Tsuji, Brian T; Brown, Tanya; Parasrampuria, Ridhi; Brazeau, Daniel A; Forrest, Alan; Kelchlin, Pamela A; Holden, Patricia N; Peloquin, Charles A; Hanna, Debra; Bulitta, Jurgen B

    2012-07-01

    Front loading is a strategy used to optimize the pharmacodynamic profile of an antibiotic through the administration of high doses early in therapy for a short duration. Our aims were to evaluate the impact of front loading of linezolid regimens on bacterial killing and suppression of resistance and on RNAIII, the effector molecule of the accessory gene regulator system (encoded by agr) in methicillin-resistant Staphylococcus aureus (MRSA). Time-killing experiments over 48 h were utilized for linezolid against four strains of MRSA: USA100, USA300, USA400, and ATCC 29213. A hollow-fiber infection model simulated traditional and front-loaded human therapeutic regimens of linezolid versus USA300 at 10(6) CFU/ml over 240 h. Over 48 h in time-kill experiments, linezolid displayed bacteriostatic activity, with reductions of >1 log(10) CFU/ml for all strains. Front-loaded regimens that were administered over 5 days, 1,200 mg every 12 h (q12h) (total, 10 doses) and 2,400 mg q12h (total, 10 doses) followed by 300 mg q12h thereafter, resulted in sustained bactericidal activity, with reductions of the area under the CFU curve of -6.15 and -6.03, respectively, reaching undetectable limits at the 10-day study endpoint. All regimens displayed a reduction in RNAIII relative expression at 24 h and 240 h compared with that of the growth control. Monte Carlo simulations predicted a <1.27× increase in the fractional decreases in platelets for all front-loaded regimens versus the 600 mg q12h regimen, except for the highest-dose front-loaded regimen. Front-loading strategies for linezolid are promising and may be of utility in severe MRSA infections, where early aggressive therapy is necessary.

  17. Impact of HAART and CNS-penetrating antiretroviral regimens on HIV encephalopathy among perinatally infected children and adolescents

    PubMed Central

    Patel, Kunjal; Ming, Xue; Williams, Paige L.; Robertson, Kevin R.; Oleske, James M.; Seage, George R.

    2010-01-01

    Objectives Prior to antiretroviral treatment, HIV-infected children frequently developed encephalopathy, resulting in debilitating morbidity and mortality. This is the first large study to evaluate the impact of HAART and central nervous system (CNS)-penetrating antiretroviral regimens on the incidence of HIV encephalopathy and survival after diagnosis of HIV encephalopathy among perinatally infected children. Design A total of 2398 perinatally HIV-infected children with at least one neurological examination were followed in a US-based prospective cohort study conducted from 1993 to 2007. Methods Trends in incidence rates over calendar time were described and Cox regression models were used to estimate the effects of time-varying HAART and CNS-penetrating antiretroviral regimens on HIV encephalopathy and on survival after diagnosis of HIV encephalopathy. Results During a median of 6.4 years of follow-up, 77 incident cases of HIV encephalopathy occurred [incidence rate 5.1 cases per 1000 person-years, 95% confidence interval (CI) 4.0–6.3]. A 10-fold decline in incidence was observed beginning in 1996, followed by a stable incidence rate after 2002. HAART regimens were associated with a 50% decrease (95% CI 14–71%) in the incidence of HIV encephalopathy compared with non-HAART regimens. High CNS-penetrating regimens were associated with a substantial survival benefit (74% reduction in the risk of death, 95% CI 39–89%) after HIV encephalopathy diagnosis compared with low CNS-penetrating regimens. Conclusion A dramatic decrease in the incidence of HIV encephalopathy occurred after the introduction of HAART. The use of HAART was highly effective in reducing the incidence of HIV encephalopathy among perinatally infected children and adolescents. Effective CNS-penetrating antiretroviral regimens are important in affecting survival after diagnosis of HIV encephalopathy. PMID:19644348

  18. The Technique, Resources and Costs of Stereotactic Body Radiotherapy of Prostate Cancer: A Comparison of Dose Regimens and Delivery Systems.

    PubMed

    Sharieff, Waseem; Greenspoon, Jeffrey N; Dayes, Ian; Chow, Tom; Wright, James; Lukka, Himu

    2016-02-01

    Robotic system has been used for stereotactic body radiotherapy (SBRT) of prostate cancer. Arc-based and fixed-gantry systems are used for hypofractionated regimens (10-20 fractions) and the standard regimen (39 fractions); they may also be used to deliver SBRT. Studies are currently underway to compare efficacy and safety of these systems and regimens. Thus, we describe the technique and required resources for the provision of robotic SBRT in relation to the standard regimen and other systems to guide investment decisions. Using administrative data of resource volumes and unit prices, we computed the cost per patient, cost per cure and cost per quality adjusted life year (QALY) of four regimens (5, 12, 20 and 39 fractions) and three delivery systems (robotic, arc-based and fixed-gantry) from a payer's perspective. We performed sensitivity analyses to examine the effects of daily hours of operation and in-room treatment delivery times on cost per patient. In addition, we estimated the budget impact when a robotic system is preferred over an arc-based or fixed-gantry system. Costs of SBRT were $6333/patient (robotic), $4368/patient (arc-based) and $4443/patient (fixed-gantry). When daily hours of operation were varied, the cost of robotic SBRT varied from $9324/patient (2 hours daily) to $5250/patient (10 hours daily). This was comparable to the costs of 39 fraction standard regimen which were $5935/patient (arc-based) and $7992/ patient (fixed-gantry). In settings of moderate to high patient volume, robotic SBRT is cost effective compared to the standard regimen. If SBRT can be delivered with equivalent efficacy and safety, the arc-based system would be the most cost effective system.

  19. Daclatasvir-based Treatment Regimens for Hepatitis C Virus Infection: A Systematic Review and Meta-Analysis

    PubMed Central

    Alavian, Seyed Moayed; Rezaee-Zavareh, Mohammad Saeid

    2016-01-01

    Context Direct acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus (HCV) infection, which is a major public health problem. Among the known DAAs, daclatasvir (DCV), an inhibitor of the non-structural 5A protein, has been used in combination with several drugs for treatment of infection with HCV of different genotypes under different conditions. We conducted a systematic review and meta-analysis of combination therapy with DCV. Evidence Acquisition We performed a systematic search in PubMed, Scopus, Science Direct and Web of Science with appropriate keywords for DCV. Studies that evaluated any regimen containing DCV and reported the sustained virological response (SVR) 12 weeks after therapy based on the HCV genotype, treatment duration and use of ribavirin (RBV) were included. The selected studies were considered for meta-analysis using STATA 11.0. Results We found six different regimens containing DCV: DCV/asunaprevir (ASV), DCV/ASV/beclubavir, DCV/pegylated interferon lambda or alpha/RBV with or without ASV, DCV/simeprevir, DCV/VX-135 and DCV/sofosbuvir (SOF). Most of these regimens were used for the treatment of HCV genotype 1 infections, and in most cases, treatment failure was noted in subtype 1a infections. Among all these regimens, DCV/SOF with or without RBV for 12 or 24 weeks was found to be an efficacious approach for treatment of different types of patients with infections with different HCV genotypes. Conclusions Among the treatment regimens containing DCV, DCV/SOF has the highest SVR rate for the treatment of infection with different HCV genotypes in different patient contexts; thus, this regimen shows promise for the treatment of HCV infections. PMID:27826322

  20. Impacts of 12-dose regimen for latent tuberculosis infection: Treatment completion rate and cost-effectiveness in Taiwan.

    PubMed

    Huang, Yi-Wen; Yang, Shun-Fa; Yeh, Yen-Po; Tsao, Thomas Chang-Yao; Tsao, Shih-Ming

    2016-08-01

    Treatment of latent tuberculosis infection (LTBI) is essential for eradicating tuberculosis (TB). Moreover, the patient adherence is crucial in determining the effectiveness of TB control. Isoniazid given by DOTS daily for 9 months (9H) is the standard treatment for LTBI in Taiwan. However, the completion rate is low due to the long treatment period and its side effects. The combined regimen using a high dose of rifapentine/isoniazid once weekly for 12 weeks (3HP) has been used as an alternative treatment option for LTBI in the United States. This may result in a higher completion rate. In this pilot study, patient adherence and cost of these 2 treatment regimens were investigated. Thus, we aimed to assess the treatment completion rate and costs of 3HP and compare to those with 9H.Data from 691 cases of LTBI treatments including 590 cases using the conventional regimen and 101 cases with rifapentine/Isoniazid were collected. The cost was the sum of the cost of treatment with Isoniazid for 9 months or with rifapentin/Isoniazid for 3 months of all contacts. The effectiveness was the cost of cases of tuberculosis avoided.In this study, the treatment completion rate for patients prescribed with the 3 months rifapentine/isoniazid regimen (97.03%) was higher than those given the conventional 9-month isoniazid regimen (87.29%) (P <0.001). The cost of 3HP and 9H was US$261.24 and US$717.3, respectively. The cost-effectiveness ratio with isoniazid for 9 months was US$ 15392/avoided 1 case of tuberculosis and US$ 5225/avoided 1 case of tuberculosis with 3HP. In addition, when compared with the conventional regimen, there were fewer patients discontinued with rifapentine/isoniazid regimen due to undesirable side effects.This was the first study to compare the 2 treatment regimens in Taiwan, and it showed that a short-term high-dosage rifapentine/isoniazid treatment regimen reduced costs and resulted in higher treatment completion than the standard LTBI isoniazid treatment.

  1. Pretreatment serum human chorionic gonadotropin cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy

    PubMed Central

    Kim, Junhwan; Jung, Young Mi; Lee, Da Yong

    2017-01-01

    Objective To investigate individual pretreatment serum human chorionic gonadotropin (hCG) cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy. Methods Eighty-five women who received methotrexate for the treatment of tubal ectopic pregnancy during 2003 to 2015 were selected. Fifty-three women received a single-dose regimen and 32 women received a multi-dose regimen. Medical treatment failure was defined as necessity of surgical treatment. The medical treatment success rate was estimated in both regimens and the pretreatment serum hCG titer to predict the success was assessed by receiver operating characteristics curve analysis. Results Pretreatment clinical and laboratory parameters were similar between group of single-dose regimen and multi-dose regimen. Treatment success rate was 64.2% in the single-dose regimen group and 71.9% in the multi-dose regimen group (P>0.05). Pretreatment serum hCG titer was an independent prognostic factor for treatment success in each regimen. Serum hCG cutoff value to predict the treatment success was 3,026 IU/L in single-dose regimen group and 3,711 IU/L in multi-dose regimen group. Conclusion We recommend use of single-dose regimen when pretreatment serum hCG <3,026 IU/L but multi-dose regimen may be favored when initial serum hCG level between 3,026 and 3,711 IU/L. PMID:28217676

  2. Economic evaluation of 3-drug antiretroviral regimens for the prevention of mother-to-child HIV transmission in Thailand.

    PubMed

    Werayingyong, Pitsaphun; Phanuphak, Nittaya; Chokephaibulkit, Kulkunya; Tantivess, Sripen; Kullert, Nareeluk; Tosanguan, Kakanang; Butchon, Rukmanee; Voramongkol, Nipunporn; Boonsuk, Sarawut; Pilasant, Songyot; Kulpeng, Wantanee; Teerawattananon, Yot

    2015-03-01

    The current program for prevention of mother-to-child HIV transmission in Thailand recommends a 2-drugs regimen for HIV-infected pregnant women with a CD4 count >200 cells/mm(3). This study assesses the value for money of 3 antiretroviral drugs compared with zidovudine (AZT)+single-dose nevirapine (sd-NVP). A decision tree was constructed to predict costs and outcomes using the governmental perspective for assessing cost-effectiveness of 3-drug regimens: (1) AZT, lamivudine, and efavirenz and (2) AZT, 3TC, and lopinavir/ritonavir, in comparison with the current protocol, AZT+sd-NVP. The 3-drug antiretroviral regimens yield lower costs and better health outcomes compared with AZT+sd-NVP. Although these 3-drug regimens offer higher program costs and health care costs for premature birth, they save money significantly in regard to pediatric HIV treatment and treatment costs for drug resistance in mothers. The 3-drug regimens are cost-saving interventions. The findings from this study were used to support a policy change in the national recommendation.

  3. The impact of the new antiviral regimens on patient reported outcomes and health economics of patients with chronic hepatitis C.

    PubMed

    Younossi, Zobair; Henry, Linda

    2014-12-15

    Hepatitis C is an important cause of chronic liver disease worldwide with an estimated 170 million people infected. Hepatitis C virus (HCV)-infected patients are physically and mentally impacted by fatigue, depression and anxiety causing an impairment of health related quality of life (HRQOL), lower worker productivity and other patient reported outcomes (PROs). Although anti-HCV regimens containing first generation direct acting antiviral agents (DAAs) were associated with significant side effects, the second generation DAAs, sofosbuvir (SOF) and simeprevir (SMV), are associated with fewer side effects, better tolerability and high cure rates. Despite these advantages, key stakeholders are currently trying to find ways to best integrate these new therapeutic regimens into the management of patients with chronic hepatitis C for the benefit of all. The purpose of this article is to offer insight into the other key and equally important outcomes (PRO's, HRQOL and cost) which should be considered when assessing the applicability of these new regimens for the care of patients infected with HCV. Our review provides evidence that the new treatment regimens for HCV not only have high efficacy rates but are also associated with better patient reported outcomes and cost per case of HCV cured. Additionally, compared to other medical interventions, these new regimens are cost-effective from a societal perspective.

  4. Effect of levofloxacin prophylaxis for prevention of severe infections in multiple myeloma patients receiving bortezomib-containing regimens.

    PubMed

    Jung, Sung-Hoon; Kang, Seung-Ji; Jang, Hee-Chang; Ahn, Jae-Sook; Yang, Deok-Hwan; Lee, Seung-Shin; Kim, Yeo-Kyeoung; Kim, Hyeoung-Joon; Lee, Je-Jung

    2014-11-01

    Fluoroquinolone is recommended as a prophylactic antibiotic for high-risk patients with profound neutropenia. We previously reported that multiple myeloma (MM) patients who received bortezomib-based regimens were at higher risk of severe infections (30.9%) associated with lymphocytopenia. In the study, we evaluated whether severe infectious complications can be prevented by prophylactic administration of oral levofloxacin in MM patients treated with bortezomib-based regimens. A total of 80 patients received oral levofloxacin 500 mg daily during the median four cycles of treatment. The prophylactic group (n = 80) with levofloxacin showed significantly decreased severe infections compared to a historical control group (n = 139) without levofloxacin prophylaxis during treatment of bortezomib-based regimens (17.5 vs. 30.9%, P = 0.037). In the prophylactic group, two patients (2.5%) died of pneumonia and septic shock. Four patients (5%) stopped levofloxacin due to side effects that consisted of gastrointestinal discomfort (2.5%), itching sense (1.25%), and QTc prolongation (1.25%). In conclusion, prophylaxis with levofloxacin may be effective in the prevention of severe infection in MM patients receiving bortezomib-based regimens. A prospective randomized study is needed to test the prophylactic effect of levofloxacin in MM patients treated with bortezomib-based regimens.

  5. Continuous or discontinuous tranexamic acid effectively inhibits fibrinolysis in children undergoing cardiac surgery with cardiopulmonary bypass.

    PubMed

    Couturier, Roland; Rubatti, Marina; Credico, Carmen; Louvain-Quintard, Virginie; Anerkian, Vregina; Doubine, Sylvie; Vasse, Marc; Grassin-Delyle, Stanislas

    2014-04-01

    Tranexamic acid is given continuously or discontinuously as an anti-fibrinolytic therapy during cardiac surgery, but the effects on fibrinolysis parameters remain poorly investigated. We sought to assess the effects of continuous and discontinuous tranexamic acid on fibrinolysis parameters in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Children requiring cardiac surgery or repeat surgery by sternotomy with CPB for congenital heart disease were randomized to receive either continuous or discontinuous tranexamic acid. Blood tranexamic acid, D-dimers, tissue plasminogen activator (tPA), tPA-plasminogen activator inhibitor 1 (tPA-PAI1) complexes, fibrinogen and fibrin monomers were measured and compared to values obtained from children who did not receive tranexamic acid. Tranexamic acid inhibited the CPB-induced increase in D-dimers, with a similar potency between continuous and discontinuous regimens. Time courses for tPA, fibrin monomers, and fibrinogen were also similar for both regimen, and there was a significant difference in tPA-PAI1 complex concentrations at the end of surgery, which may be related to a significantly higher tranexamic acid concentration. Continuous and discontinuous regimen are suitable for an effective inhibition of fibrinolysis in children undergoing cardiac surgery with CPB, but the continuous regimen was previously shown to be more effective to maintain stable tranexamic acid concentrations.

  6. New Regimen for Continuous Infusion of Vancomycin in Critically Ill Patients

    PubMed Central

    Cristallini, Stefano; Hites, Maya; Kabtouri, Hakim; Roberts, Jason A.; Beumier, Marjorie; Cotton, Frederic; Lipman, Jeffrey; Jacobs, Frédérique; Vincent, Jean-Louis; Creteur, Jacques

    2016-01-01

    Despite the development of new agents with activity against Gram-positive bacteria, vancomycin remains one of the primary antibiotics for critically ill septic patients. Because sepsis can alter antimicrobial pharmacokinetics, the development of an appropriate dosing strategy to provide adequate concentrations is crucial. The aim of this study was to prospectively validate a new dosing regimen of vancomycin given by continuous infusion (CI) to septic patients. We included all adult septic patients admitted to a mixed intensive care unit (ICU) between January 2012 and May 2013, who were treated with a new vancomycin CI regimen consisting of a loading dose of 35 mg/kg of body weight given as a 4-h infusion, followed by a daily CI dose adapted to creatinine clearance (CrCL), as estimated by the Cockcroft-Gault formula (median dose, 2,112 [1,500 to 2,838] mg). Vancomycin concentrations were measured at the end of the loading dose (T1), at 12 h (T2), at 24 h (T3), and the day after the start of therapy (T4). Vancomycin concentrations of 20 to 30 mg/liter at T2, T3, and T4 were considered adequate. A total of 107 patients (72% male) were included. Median age, weight, and CrCL were 59 (interquartile range [IQR], 48 to 71) years, 75 (IQR, 65 to 85) kg, and 94 (IQR, 56 to 140) ml/min, respectively. Vancomycin concentrations were 44 (IQR, 37 to 49), 25 (IQR, 21 to 32), 22 (IQR, 19 to 28), and 26 (IQR, 22 to 29) mg/liter at T1, T2, T3, and T4, respectively. Concentrations were adequate in 56% (60/107) of patients at T2, in 54% (57/105) at T3, and in 73% (41/56) at T4. This vancomycin regimen permitted rapid attainment of target concentrations in serum for most patients. Concentrations were insufficient in only 16% of patients at 12 h of treatment. PMID:27216073

  7. Using Monte Carlo simulation to determine optimal dosing regimen for cefetamet sodium for injection.

    PubMed

    Li, Caizheng; Sun, Jiayu; Miao, Jia; Qin, Yongping; Wang, Ying; Yu, Rujia; Xiao, Yonghong

    2016-06-01

    The objective of the study was to use Monte Carlo simulation to determine the optimal treatment dosing regimen of the cefetamet sodium for injection by analysing the pharmacokinetics (PK) parameters in healthy Chinese volunteers, and antibacterial activity in vitro was also examined. A three-cross Latin square single-dose PK study was designed. Twelve healthy volunteers were randomized to receive 500, 1000, and 2000 mg of cefetamet sodium for IV infusion over 30 minutes in three periods sequentially; and the washout time in between periods was 3 days. The drug concentrations in plasma were analysed by high-performance liquid chromatography, and the PK parameters were calculated using DAS2.0 PK software. The peak concentrations (Cmax) at 0.5 hours were 37.78±7.29, 76.18±12.81, and 149.32±29.94 mg/l, the areas under concentration-time curve (AUC0-t) were 69.75±14.44, 139.06±22.62, and 278.54±53.12 mg h/l, and the elimination half-life (t1/2) were 1.69±0.19, 1.69±0.27, and 1.81±0.23 hours for 500, 1000, and 2000 mg of cefetamet sodium for injection, respectively. The disposition of cefetamet was appear to fit a two-compartment model with linear kinetics. Antibacterial activity in vitro showed that most Gram-negative bacteria, including non-extended-spectrum beta-lactamases (ESBL)-producing Enterobacter, Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae, were sensitive to cefetamet. The result of Monte Carlo simulation showed that the probability of target attainment for bactericidal response (%fT>MIC≧50%) for susceptible bacteria was reached at all three dosing regimens of 500 mg, q6h, 1000 and 2000 mg, q8h and q6h. Considering the efficacy, safety, and pharmacoeconomy comprehensively, we recommended the dosing regimen of 500 mg, q6h for further clinical treatment based on the principle of minimum daily dosage.

  8. Transplant-finalized salvage of adult acute lymphoblastic leukemia: results of a mitoxantrone- and methotrexate-based regimen in 36 patients.

    PubMed

    Di Bona, Eros; Pogliani, Enrico; Rossi, Giuseppe; Lerede, Teresa; D'Emilio, Anna; Vespignani, Michele; Rodeghiero, Francesco; Barbui, Tiziano; Bassan, Renato

    2005-06-01

    Idarubicin-based induction programs in acute lymphoblastic leukemia (ALL) account for 75?-?85% of complete remission rate. A small amount of patients exhibit primary refractoriness, and approximately 60% of those achieving a remission eventually relapse. The present study aimed to review the outcome of patients relapsing after or resistant to an idarubicin-based, induction-consolidation regimen (with/without additional high dose cytarabine). The 'ABC' phase II trial consisted of mitoxantrone (50 mg/m(2) over 5 days) associated with high-dose methotrexate (1.5 g/m(2) over 24 h, followed by folinic acid rescue), high-dose methyl-prednisolone (125 mg b.i.d.) and vincristine, plus granulocyte colony-stimulating factor. Eligible patients were treated with two courses ('A' and 'B', the latter with reduced drug dosages), followed by allogeneic or autologous haematopoietic stem cell transplantation (HSCT, 'C'). Thirty-six patients (3 primary resistant, 33 at first marrow relapse) were evaluated. With 'A', 21 achieved a complete remission (CR), 10 were refractory and 5 died early. Eighteen patients received 'B' (with one more CR, for an overall CR rate of 61%) and, eventually, 12 patients had 'C' procedures (7 autologous, 5 allogeneic HSCT). WHO grade >or=3 treatment-related toxicity developed in 50% and 34% of 'A' an