Effects of high-dose baclofen on cue reactivity in alcohol dependence: A randomized,placebo-controlled pharmaco-fMRI study

Increased functional brain response towards alcohol-associated stimuli is a neural hallmark of alcohol dependence and a promising target for pharmacotherapy. For the first time, we assessed the effects of individually titrated high-dose baclofen on cue reactivity and functional connectivity in alcohol-dependent (AD) patients in a randomized controlled trial (RCT).We investigated 23 recently detoxified AD patients and 23 matched healthy controls (HC) with a cue reactivity functional magnetic resonance imaging task. Patients were further scanned at baseline without medication and during treatment with high-dose baclofen/placebo (30–270 mg/d). Analyses were conducted for alcohol cue-elicited brain response, alcohol cue-modulated and stimulus-independent functional connectivity with left ventral tegmental area (VTA) as seed region.At baseline, AD patients (N?=?23) showed increased cue-elicited brain activation in the ventral striatum (VS) compared to HC (N?=?23), which was decreased at the second scanning session compared to baseline. Patients receiving baclofen (N?=?10) showed a significant stronger decrease in cue-elicited brain activation in left orbitofrontal cortex (OFC), bilateral amygdala and left VTA than patients receiving placebo (N?=?13). Treatment with baclofen further led to a decrease in alcohol cue-modulated functional connectivity between left VTA and left anterior cingulate cortex (ACC) as well as left medial prefrontal cortex (MPFC). Regarding clinical outcome, significantly more patients of the baclofen group remained abstinent during the high-dose period.Baclofen specifically decreased cue-elicited brain responses in areas known to be involved in the processing of salient (appetitive and aversive) stimuli. Treatment with high-dose baclofen seems to provide a pharmacological relief of this neural “warning signal” evoked by alcohol-related cues, thereby possibly supporting patients in remaining abstinent.Trial Registration Identifier of the main trial [BACLAD study] at clinicaltrials.gov: NCT01266655.     

A randomized clinical trial comparing enamel matrix derivative and membrane treatment of buccal Class II furcation involvement in mandibular molars. Part I: Study design and results for primary outcomes

BACKGROUND: The objective of this multicenter, randomized trial was to compare enamel matrix derivative (EMD; test) with barrier membranes (control) for the treatment of mandibular buccal Class II furcation defects. METHODS: Forty-five patients with 90 comparable defects on contralateral molars were included. Defects were randomly assigned to EMD or bioabsorbable barrier membrane; the contralateral defect received the alternative treatment. Assessments at baseline and 8 and 14 months included gingival margin levels, probing depths, bleeding on probing, vertical attachment levels, and vertical bone sounding from a stent at five buccal sites/ tooth. Defect dimensions were recorded at surgery and during reentry at 14 months. Change of open horizontal furcation depth was the primary outcome variable. Adverse reactions and patient perceptions were also noted. RESULTS: Both treatment modalities led to significant clinical improvements. The median reduction of open horizontal furcation depth was 2.8 mm with the corresponding interquartile interval (1.5 mm, 3.5 mm) at test sites compared with 1.8 mm (1.0 mm, 2.8 mm) at control sites. The Hodges-Lehmann estimator of the advantage (reduction test versus control) was 0.75 mm (95% confidence interval [CI]: 0.125 mm, 1.375 mm, P = 0.033, Wilcoxon). The frequency of complete furcation closure was 8/45 (test) and 3/45 (control); partial closure, 27/45 in both groups; no change, 9/45 and 11/45, respectively; and deterioration, 1/45 and 4/45, respectively. The frequency of no pain or no swelling at 1 week post-surgery was 62% and 44%, respectively, at the test sites and 12% and 6% at the control sites. CONCLUSION: There was a significantly greater reduction in horizontal furcation depth and a comparatively lower incidence of postoperative pain/swelling following enamel matrix derivative compared to membrane therapy.     

Evaluation of a new bioabsorbable barrier for recession therapy: a feasibility study

BACKGROUND: The objective of this study was to evaluate the feasibility of a new polylactic acid bioabsorbable barrier in the treatment of gingival recession. METHODS: Twenty patients with buccal recession defects (Miller class I, II, and III; mean recession: 4.0 +/- 1.2 mm; range: 2.0 to 6.8 mm) participated. After thorough scaling and root surface conditioning with 10% tetracycline-HCl, a trapezoidal mucoperiosteal flap was prepared. A customized barrier was applied to cover the defect. Barriers adhered directly to tooth and bone and no sutures were used. The barrier was subsequently covered by a coronally positioned flap. Assessments of probing depths were performed by means of a controlled-force electronic probe, and recession was determined on stone models with a digital caliper at baseline and 12 months following therapy. RESULTS: Eight barriers showed limited exposure (1 to 2 mm) with minimal signs of gingival inflammation between 2 and 6 weeks following surgery. Comparing baseline measurements with outcomes at 12 months, significant root coverage and probing attachment gain were observed (P <0.0001, paired t test). Mean gingival recession was reduced to 0.4 +/- 0.5 mm, corresponding to a mean root coverage of 91.9%, and overall attachment gains amounted to 4.2 mm. A significant gain of keratinized tissue was found (2.9 +/- 0.7 mm), and mean probing depths were slightly reduced from 2.2 to 1.7 mm. CONCLUSIONS: The results of this study indicate favorable outcomes after using a new bioabsorbable barrier material for root coverage in recession-type defects.     

Effects of hydrogen peroxide bleaching strip gels on dental restorative materials in vitro: surface microhardness and surface morphology

OBJECTIVE: This study examined the effects of peroxide tooth bleaching, including Crest Whitestrips hydrogen peroxide gel treatments, on the surface hardness and morphology of common dental restorative treatments. METHODOLOGY: American Dental Association (ADA) recommended dental restorative materials, including amalgam, dental gold, porcelain, glass ionomer, and composites, were prepared according to manufacturers' instructions. A cycling treatment methodology was employed which alternated ex vivo human salivary exposures with bleaching treatments under conditions of controlled temperature and durations of treatment. Bleaching treatments included commercial Crest Whitestrips bleaching gels, which utilize hydrogen peroxide as the in situ bleaching source, and several commercial carbamide peroxide bleaching gels. Control treatments included placebo gels and an untreated group. Crest Whitestrips bleaching included treatment exposures simulating recommended clinical exposures (14 hours), along with excess bleaching simulating exposure to five times suggested Crest Whitestrips use. At the conclusion of treatments, surface microhardness measures and surface morphological assessments with standard and variable pressure (VP-) SEMs were conducted to assess the effects of bleaching exposure on the surface morphology and structural integrity of the restoratives. RESULTS: Surface microhardness and SEM measures revealed no significant deleterious effects on the restoration surfaces from Whitestrips gels. CONCLUSION: These results confirm that tooth bleaching from the selected commercial hydrogen peroxide or carbamide peroxide bleaching systems does not produce changes in surface morphology or microhardness of common dental restorative materials. These results support the clinical safety of the selected commercial bleaching systems to the oral environment, matching results obtained from long-term use of these ingredients applied in dental offices and available in commercial formulations.     

Pharmacokinetic profile of a locally administered doxycycline gel in crevicular fluid,blood, and saliva

BACKGROUND: With the help of so-called controlled release delivery systems, the half-life period of locally administered antibiotics in gingival crevicular fluid (GCF) can be extended significantly. The aim of this study was to characterize the delivery profile of a new one-component 14% doxycycline free amine gel for local application. Pharmacokinetics of doxycycline (DOXY) were analyzed in GCF, saliva, and serum. METHODS: Twenty patients with persisting or recurring pockets (probing depths > or = 5 mm and bleeding on probing) after mechanical treatment (surgical or non-surgical) took part in the study. In each patient 1 periodontal defect was treated with DOXY gel. Samples of GCF, saliva, and serum were obtained before application of DOXY gel; 15 minutes after application; at 2 and 5 hours; and at 1, 2, 3, 4, 7, 9, and 11 days after application. Separation and quantitative measurement of DOXY was performed with high performance liquid chromatography and UV detection at lambda = 260 nm. RESULTS: Coefficients of variation were lower than 2% (intraassay) and 4% (interassay), respectively. For concentrations between 50 to 1000 microg/ml, we found a linear relationship between expected and measured DOXY values (linear coefficient of correlation: r = 0.998). Within the first 5 hours after application, concentration of DOXY in GCF (maximum after 15 minutes 19.97 +/- 5.85 mg/ml) and saliva (maximum after 15 minutes 17.83 +/- 2.84 mg/ml) was similar. Then concentration fell to a lower level (28.90 +/- 19.44 microg/ml) compared to GCF (577.41 +/- 127.34 microg/ml) after 3 days. Up to 10 days after application, the concentration of DOXY in GCF was 34.24 microg/ml. With the exception of 1 patient, all serum samples were DOXY-negative. CONCLUSIONS: 1) After subgingival application of biodegradable 14% doxycycline gel, mean doxycycline levels in GCF that exceeded 16 microg/ml could be maintained for at least 12 days. Thus, the antimicrobial agent may be classified as a controlled release device. 2) The antibiotic effect was limited mainly to the subgingival sites of application of the doxycycline gel. 3) The doxycycline gel possesses the pharmacokinetic and clinical properties to deliver efficacious levels of antibiotics to the periodontal pocket and to maintain these levels for at least 1 week without the need of further drug retention by a periodontal dressing.     

The effects of high concentration tooth whitening bleaches on microleakage of Class V composite restorations

OBJECTIVE: To explore the effects of high-concentration hydrogen peroxide bleaching agents on the microleakage of composite restorations. METHODS: In 60 extracted human molars, Class V restorations were prepared with Scotchbond 1/Filtek Z250 composite. Teeth were randomly divided into four groups: (1) no bleaching; (2) bleaching with 14% hydrogen peroxide gel from Crest Whitestrips; (3) bleaching with 20% carbamide peroxide gel from Opalescence PF 20; and (4) bleaching with 38% hydrogen peroxide gel Opalescence Xtra Boost. Bleaching procedures were carried out at 37 degrees C for 21 days/42 hours (2); seven days/42 hours (3); one day/45 minutes (4). Varnish was applied on the apical portion of the teeth only, excluding the restoration, prior to immersion in a 0.1% rhodamin-B-isothiocyanate solution for 24 hours at 37 degrees C. After rinsing, specimens were embedded in methacrylate blocks, and sectioned with a water-cooled microtome with three restoration cuts positioned centrally parallel to the long axis of the tooth. Microleakage was evaluated at the occlusal margins of the Class V restorations using a stereo microscope, separate for dentin and enamel margins. RESULTS: Over 90% of enamel margins exhibited no microleakage following cycling. Bleaching agents had almost no effect on numerical averages. Eighty-eight percent of the dentin margins were free of microleakage for the non-treated control group. Bleaching treatments collectively had slight numerical reductions to around 80%. The statistical evaluation (Kruskal-Wallis-test) showed no significant difference in microleakage between groups for enamel or dentin. CONCLUSION: Bleaching with the materials tested had no influence on microleakage of Filtek Z250 composite bonded with Scotchbond 1.     

Microradiography and confocal laser scanning microscopy applied to enamel lesions formed in vivo with and without fluoride varnish treatment

Abstract The aim of the present investigation was to combine 2 techniques suitable for lesion characterization: quantitative microradiography (TMR) and confocal laser scanning microscopy (CLSM) on in vivo induced lesions with and without a fluoride varnish (Duraphat®) treatment. Orthodontic bands were attached to premolars to be extracted for orthodontic reasons to induce enamel caries on the buccal surfaces. In the caries development part of the study, 1 tooth of each pair received at the start 1 topical application with the fluoride varnish Duraphat®, the contralateral tooth serving as untreated control. All teeth were extracted after 4 weeks. In the caries progression part, the premolars were banded for 4 weeks without any treatment to induce caries. 1 premolar in each pair was then extracted and analyzed. The contralateral tooth received one Duraphat® application and was extracted after another 2 weeks. In the caries development part of the study. TMR analysis showed that the Duraphat® treatment on sound enamel reduced lesion depth by 48% compared to the untreated control. In the caries progression part, no significant difference was found between the untreated teeth extracted after 4 weeks and the fluoride treated lesions extracted after another 2 weeks. CLSM images agreed well with the TMR measurements. In the fluoride treated lesions, the CLSM images showed more light scattering indicating precipitation of material.