Effect of ozone to remineralize initial enamel caries: in situ study.

OBJECTIVES: Effect of ozonated water in remineralizing artificially created initial enamel caries was investigated using laser fluorescence and polarized light microscopy in an in situ study. MATERIALS AND METHODS: Teeth specimens (buccal sections) were immersed in 5-ml solution of 2 mM CaCl2, 2 mM NaH2P04, and 50 mM CH3COOH at pH of 4.55 for 5 h in an incubator at 37° to create subsurface demineralization. After which, they were randomly allocated into one of the following remineralization regimens: ozone (ozonated water 0.1 mg/l and 10 % nano-hydroxyapatite paste, Aclaim(TM)), without ozone (only 10 % nano-hydroxyapatite paste, Aclaim(TM)), and control (subjects' saliva alone). Specimens were embedded in acrylic retainers worn by orthodontic patients throughout the 21-day study duration and constantly exposed to their saliva. Laser fluorescence was recorded for all the specimens at baseline, after demineralization, and remineralization using DIAGNOdent, and the results were validated using polarized microscopic examination. The results were analyzed using repeated measures, one-way ANOVA with post hoc multiple comparisons. RESULTS: Reduced DIAGNOdent scores and greater depth of remineralization following application of ozonated water and nano-hydroxyapatite were found compared to those of the without ozone and control groups (P < 0.001), and the ozone-treated group exhibited maximum remineralization under the polarized light microscopy. CONCLUSION: Ozonated water can be considered an effective agent in reversing the initial enamel caries alongside with nano-hydroxyapatite compared to nano-hydroxyapatite alone and saliva. CLINICAL RELEVANCE: Ozone water can be used to remineralize incipient carious lesions, and it enhances the remineralizing potential of nano-hydroxyapatite thereby preventing the tooth from entering into the repetitive restorative cycle.

Evaluation of instant desensitization after a single topical application over 30 days: a randomized trial.

BACKGROUND: The aim of this study was to evaluate the efficacy of ProArgin(™) (8% arginine), Gluma(®) and NovaMin(®) (5% calcium phosphosilicate) in relieving dentinal hypersensitivity immediately and over 30 days following a single topical application. METHODS: A three-cell, parallel group randomized trial was conducted among 56 patients exhibiting dentinal hypersensitivity with tooth as the unit of study. ProArgin(™) paste, Gluma(®) Desensitizer and NovaMin(®) paste were applied on randomly assigned teeth in each participant. Three stimuli were tested: tactile stimulated by running an explorer and measured using VAS (1-10 scale); air blast and cold water stimulated hypersensitivity measured using the Schiff Sensitivity Scale at baseline, immediately, 15 days and 30 days after application. Friedman test and Wilcoxon test were used for within group comparisons. Kruskal-Wallis test and Mann-Whitney U test were used for between group comparisons. RESULTS: All three groups showed significant reductions in hypersensitivity from baseline at all time points (p < 0.05). ProArgin(™) paste elicited a significantly higher reduction in hypersensitivity (p < 0.016) compared to Gluma(®) and NovaMin(®) for all stimuli at the end of 30 days. CONCLUSIONS: A single topical application of ProArgin(™) paste is significantly more effective than both a single topical application of Gluma(®) and NovaMin(®) paste in relieving dentinal hypersensitivity immediately and over 30 days.

Preclinical to clinical translation of CNS transporter occupancy of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.

BACKGROUND: Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters. METHODS: We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor. RESULTS: TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC50 of 11.7 ng/mL and 50.8 ng/mL, respectively, consistent with modest selectivity for NET in vivo. Accounting for species differences in protein binding, the projected human NET and SERT plasma EC50 values were 5.5 ng/mL and 23.9 ng/mL, respectively. A single-dose, open-label PET study (4-20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [(11)C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [(11)C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30-40 h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC50 for NET was estimated to be 1.21 ng/mL, and at doses of greater than 4 mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35 ng/mL. CONCLUSIONS: These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.

Formation of median nerve from single root on left side and communicating branch from median nerve to musculocutaneous nerve on right side.

We report here a rare variation of median nerve in an adult male cadaver observed during routine cadaveric dissection. A meticulous dissection was performed and the observations were noted. On left side, median nerve was formed from lateral cord. On right side, median nerve was formed by fusion of two slightly longer roots. The communicating branch from median nerve goes laterally to join musculocutaneous nerve. This communicating branch lies between biceps brachii and brachialis muscle and gives small branches to brachialis muscle. Knowledge of these variations is important to anatomists, radiologists, anaesthesiologists and surgeons, which may contribute to the explanation of diagnosis and surgical treatment, which can prevent any postoperative complications during surgery. The knowledge of this anatomical variation is important specially when performing plexus bloc or Latarjet's procedure.

Assay of tolnaftate and related impurities by isocratic supercritical fluid chromatography.

Tolnaftate, an antifungal drug (TF) and related impurities arising from synthesis, viz., N-methyl-m-toluidine (NMmT) and beta-naphthol-1-chlorothio carbamate (beta-NCTC) can be determined by supercritical fluid chromatography. Even though it was possible to elute TF completely with neat SCF CO2, the peaks of the impurities were found to merge. The chromatographic figures of merit of the three analytes such as retention time (tR), capacity factor (k), selectivity factor (alpha), no. of theoretical plates (N), were optimized. The three compounds can be resolved in 5 min on a Hypersil (250 x 4.0 mm) 5 mu, C18 column with supercritical carbon dioxide, modified with 1.96% methanol as the mobile phase at 9.81 MPa and at 40 degrees C. Detection was carried out at 220 nm. The data as evaluated by the linear regression least squares fit method gave linearity ranges from 0.2 to 10.0 microg/mL for TF and NMmT and 0.3 to 10.0 microg/mL for beta-NCTC with correlation coefficients > 0.99. The method was successfully employed to estimate levels of 0.01% for NMmT and 0.02% for beta-NCTC with respect to TF.

Application of packed column supercritical fluid chromatography to the simultaneous determination of seven anticonvulsant drugs.

Studies of speed, resolution, and selectivity have shown that packed column supercritical fluid chromatography (PCSFC) is a viable technique for the isocratic, isothermal and isobaric separation of seven anticonvulsants, viz., phenobarbitone, phenytoin sodium, phethenylate sodium, nitrazepam, clonazepam, carbamazepine, and primidone, and their simultaneous estimation. The drugs were eluted from a JASCO, RP-C(18) (250 x 4.6 mm) 10 micro packed column with a binary mobile phase of carbon dioxide and methanol, using ibuprofen as the internal standard. The effect of pressure, temperature, modifier concentration, and the rate of flow of CO(2) on retention and selectivity of all the analytes were studied and the parameters optimised. Without methanol in the mobile phase none of the solutes eluted. Changing modifier concentration was the most effective physical parameter for changing retention and selectivity. The analytes were detected using a UV detector at 215 nm. An arbitrary mixture of eight components was baseline resolved in approximately 7 min. The study includes a successful attempt at quantification of the drugs. Chromatographic and analytical figures of merit have been listed. The present work holds promise for a possible replacement of HPLC with SFC for the separation and assay of drugs of different families.

Packed column supercritical fluid chromatographic separation and estimation of acetaminophen, diclofenac sodium and methocarbamol in pharmaceutical dosage forms.

A reproducible and fast method has been developed for the assay of acetaminophen, methocarbamol, and diclofenac sodium in bulk and drug forms using packed column supercritical fluid chromatography employing internal standard method. The analytes were resolved by elution with supercritical fluid carbon dioxide doped with 11.1% (v/v) methanol on a Shendon-Phenyl (250x4.6 mm) 5 mum column with detection monitored spectrophotometrically at 225 nm. The densities and polarities of the mobile phase were optimised from the effects of pressure, temperature and modifier concentration on chromatograhic figures like retention time (t(R), min), retention factor (k(')) etc. Modifier concentration proved to be the most effective means for changing both retention and selectivity. Calibration data and recovery of the drug from spiked concentrations were determined to assess the viability of the method. The supercritical fluid chromatography (SFC) method was directly compared to an HPLC assay, developed in the laboratory, of the same analytes. With respect to speed and use of organic solvents SFC was found to be superior, while in all other aspects the results were similar to HPLC. The method has been successfully used for the assay of two formulations containing a combination of (A) acetaminophen and methocarbamol and (B) acetaminophen and diclofenac sodium. There was no interference from excipients. The present work validates the recent proposition that supercritical fluid chromatography using CO(2) and modifiers is a viable, faster alternative to reverse phase HPLC.