bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental, Molecular, and Genetic Dissection ofINaIn Vivo in Embryonic Zebrafish Sensory Neurons
Authors: Pineda Ricardo H. , Heiser Ryan A. , Ribera Angeles B.
Published: May 2005

The presence of multiple Nav1 isotypes within a neuron and the lack of specific blockers hamper identification of the in vivo roles of sodium current ( INa) components, especially during embryonic stages. To identify the functional properties of INacomponents in vivo in developing neurons, we took a molecular genetic approach. Embryonic zebrafish Rohon–Beard (RB) mechanosensory neurons express two different sodium channel isotypes: Nav1.1 and Nav1.6. To examine the properties of Nav1.1- and Nav1.6-encoded currents in RB cells at different developmental stages, we eliminated the contribution of Nav1.6 and Nav1.1 channels, respectively, using an antisense morpholino (MO) approach. MOs were injected into one-cell stage embryos, and RB sodium currents were recorded using patch-clamp techniques in both conventional whole cell mode as well from nucleated patches. Only a subset of RB cells appeared to be affected by the Nav1.1MO. Overall, the effect of the Nav1.1MO was a small 25% average reduction in current amplitude. Further, Nav1.1MO effects were most pronounced in RB cells of younger embryos. In contrast, the effects of the Nav1.6 MO were observed in all cells and increased as development proceeded. These results indicated that developmental upregulation of RB INaentailed an increase in the number of functional Nav1.6 channels. In addition, analysis of voltage-dependent steady-state activation and inactivation parameters revealed that specific functional properties of channels were also developmentally regulated. Finally, analysis of macho mutants indicated that developmental upregulation of INawas absent in RB cells. These results indicate that MOs are a useful tool for the molecular dissection and analysis of ion channel function in vivo.
Gastric Ulcers Evoke Hyperexcitability and Enhance P2X Receptor Function in Rat Gastric Sensory Neurons
Authors: Dang K. , Bielfeldt K. , Lamb K. , Gebhart G. F.
Published: May 2005

Tissue inflammation contributes to the development of hyperalgesia, which is at least in part due to altered properties of primary afferent neurons. We hypothesized that gastric ulcers enhance the excitability of gastric sensory neurons and increase their response to purinergic agonists. The rat stomach was surgically exposed, and a retrograde tracer [1.1′-dioctadecyl-3,3,3,′3-tetramethylindocarbocyanine methanesulfonate (DiI)] was injected into the wall of the distal stomach. Kissing ulcers (KUs) were produced by a single injection of acetic acid (0.1 ml for 45 s; 60%) into the clamped gastric lumen. Saline injection served as control. Gastric nodose ganglion (NG) or dorsal root ganglion (DRG) cells were harvested 7 days later and acutely dissociated for whole cell recordings. Based on whole cell capacitance, gastric DRG neurons exhibited larger cell size than NG neurons. Significantly more control gastric DRG neurons compared with NG counterparts had TTX-resistant action potentials. Almost all control NG neurons (90%) compared with significantly less DRG neurons (≤38%) responded to ATP or α,β-metATP. Whereas none of the control cells exhibited spontaneous activity, about 20% of the neurons from KU animals generated spontaneous action potentials. KUs enhanced excitability as shown by a decrease in threshold for action potential generation, which was in part due to an increased input resistance. This was associated with an increase in the fraction of neurons with TTX-resistant action potentials and cells responding to capsaicin and purinergic agonists. KU doubled the current density evoked by the P2X receptor agonist α,β-metATP and slowed decay of the slowly desensitizing component of the current without affecting the concentration dependence of the response. These data show that KU sensitizes vagal and spinal gastric afferents by affecting both voltage- and ligand-gated channels, thereby potentially contributing to the development of dyspeptic symptoms.
Nature of the Transition Between Two Modes of External Space Perception in Tilted Subjects
Authors: Kaptein Ronald G. , Van Gisbergen Jan A. M.
Published: May 2005

A striking feature of visual verticality estimates in the dark is undercompensation for lateral body tilt. Earlier studies and models suggest that this so-called Aubert (A) effect increases gradually to around 130° tilt and then decays smoothly on approaching the inverted position. By contrast, we recently found an abrupt transition toward errors of opposite sign (E effect) when body tilt exceeded 135°. The present study was undertaken to clarify the nature of this transition. We tested the subjective visual vertical in stationary roll-tilted human subjects using various rotation paradigms and testing methods. Cluster analysis identified two clearly separate response modes (A or E effect), present in all conditions, which dominated in different but overlapping tilt ranges. Within the overlap zone, the subjective vertical appeared bistable on repeated testing with responses in both categories. The tilt range where bistability occurred depended on the direction of the preceding rotation (hysteresis). The overlap zone shifted to a smaller tilt angle when testing was preceded by a rotation through the inverted position, compared with short opposite rotations from upright. We discuss the possibility that the A-E transition reflects a reference shift from compensating line settings for the head deviation from upright to basing them on the tilt deviation of the feet from upright. In this scenario, both the A and the E effect reflect tilt undercompensation. To explain the hysteresis and the bistability, we propose that the transition is triggered when perceived body tilt, a signal with known noise and hysteresis properties, crosses a fixed threshold.
Fictive Swimming Motor Patterns in Wild Type and Mutant Larval Zebrafish
Authors: Masino Mark A. , Fetcho Joseph R.
Published: May 2005

Larval zebrafish provide a unique model for investigating the mechanisms involved in generating rhythmic patterns of behavior, such as swimming, due to the array of techniques available including genetics, optical imaging, and conventional electrophysiology. Because electrophysiological and imaging studies of rhythmic motor behaviors in paralyzed preparations depend on the ability to monitor the central motor pattern, we developed a fictive preparation in which the activity of axial motor neurons was monitored using extracellular recordings from peripheral nerves. We examined spontaneous and light induced fictive motor patterns in wild type and mutant larval zebrafish (4–6 days post-fertilization) paralyzed with curare. All spontaneous and light-induced preparations produced alternation of motor activity from side-to-side (mean contralateral phase = 50.7 ± 7.0%; mean burst frequency = 35.6 ± 4.7 Hz) and a progression of activity from head-to-tail (mean ipsilateral rostrocaudal delay = 0.8 ± 0.5 ms per segment), consistent with lateral undulation and forward propulsion during swimming, respectively. The basic properties of the motor pattern were similar in spontaneous and light-induced swimming. This fictive preparation can be used in combination with conventional electrophysiological and imaging methods to investigate normal circuit function as well as to elucidate functional deficits in mutant lines. Toward this end, we show that two accordion class mutants, accordion and bandoneon, have alternating activity on opposite sides of the body, contradicting the hypothesis that their deficit results from the absence of the reciprocal glycinergic inhibition that is typically found in the spinal cord of swimming vertebrates.
Timing Finger Opening in Overarm Throwing Based on a Spatial Representation of Hand Path
Authors: Hore Jon , Watts Sherry
Published: May 2005

Previous studies on overarm throwing have suggested that throwing accuracy depends on a precise central timing mechanism. In the present study, we investigated an alternative hypothesis: that central control of finger opening is based on an internal positional representation of handpath. Angular positions of each segment of the middle finger, thumb, and arm were recorded with the search-coil technique as subjects made slow, medium, and fast throws at a target 3.1 m away. Onset of ball release from the hand was strongly correlated with extension at the proximal interphalangeal joint (PIJ). The velocity of this finger joint opening varied with the speed of the throw. In agreement with the hypothesis, at a fixed hand angular position in space, there was no difference across subjects in the amplitude of extension at the PIJ for throws of different speeds. That is, for these two parameters, a fast throw was the same as a slow throw that was sped-up. This occurred irrespective of whether the trunk was constrained (sitting throws) or unconstrained (standing throws). No equivalent relation was found between extension at the PIJ and elbow extension. These findings support the idea that precisely timed finger opening in overarm throwing depends, not on a central timing controller that triggers a step-like (ballistic) finger opening at the right moment in throws of different speeds, but on a central spatial controller that matches angular positions of finger opening to the intended handpath.
Modulite®: A Simple Solution to a Difficult Problem
Authors: Lewis D.A. , Ganderton D. , Meakin B.J. , Brambilla G.
Published: May 2005

The development of HFA-based pMDIs has proved difficult due to differences in the physico-chemical properties of CFC and HFA propellants. However, the development of solution formulations instead of suspensions has provided a way to formulate products whose cloud characteristics can be modulated in a controlled manner by permuting different formulation and device hardware variables. The new approach has proved successful in formulating several different drugs including steroids and has now been applied to developing a formoterol Modulite® solution formulation characterized by good chemical stability, delivery performance, and clinical results.
A Randomized, Double-Blind, Double-Dummy, Single-Dose, Efficacy Crossover Trial Comparing Formoterol-HFA (pMDI) versus Formoterol-DPI (AerolizerTM) and Placebo (pMDI or AerolizerTM) in Asthmatic Patients
Authors: Bousquet J. , Huchon G. , Leclerc V. , Vicaut E. , Lefrançois G.
Published: May 2005

Background: Chlorofluorocarbons (CFCs) have traditionally been used as propellants in pressurized metered- dose inhalers (pMDIs), which are often used to deliver drugs to the lungs for the treatment of reversible obstructive airways diseases. However, CFCs are harmful to the environment and need to be phased out. Hydrofluoroalkanes (HFAs), such as HFA-134a, represent a safe alternative to CFC propellants for use with pMDIs. Formoterol fumarate has been recently formulated in an HFA-134a-containing pMDI and is undergoing clinical testing with the aim of providing an effective, safe and environmentally-friendly alternative to currently existing formulations. Objectives: The study objective was to demonstrate the non-inferiority (clinical equivalence) of the HFA-134a-propelled formoterol pMDI versus the formoterol Aerolizer™ dry powder inhaler (DPI). Methods: The study was a single dose, double-blind, double-dummy, randomized, placebo and reference product controlled, three-periods, crossover trial in 49 patients with moderate-to-severe stable asthma. The active treatments involved a single 12-µg dose of formoterol delivered from an HFA-134a-propelled pMDI and an Aerolizer™ DPI. The primary efficacy parameter was the average 12-hour forced expiratory volume in 1 s (FEV1), calculated as area under the 12-hour post-morning dose FEV1 time curve divided by time (hours). Results: Mean 12-hour average FEV1 was 2.28 liters for placebo, 2.60 liters for formoterol pMDI and 2.60 liters for the formoterol DPI. Contrast analysis showed that the HFA-propelled formoterol pMDI was significantly superior to placebo in terms of 12-hour average FEV1. Further statistical analysis confirmed bronchodilation with the pMDI formoterol formulation which was clinically equivalent to that seen with the DPI formoterol formulation. All treatments were well tolerated. Conclusions: The bronchodilatory effect of a 12-µg dose of formoterol inhaled from a CFC-free, HFA-propelled pMDI is significantly superior to placebo and equivalent to a commercially available formoterol DPI.
A Randomized, Double-Blind, Double-Dummy, Single-Dose, Crossover Trial Evaluating the Efficacy and Safety Profiles of Two Dose Levels (12 and 24 μg) of Formoterol-HFA (pMDI) vs. Those of a Dose Level (24 μg) of Formoterol-DPI (Foradil®/Aerolizer™) and of Placebo (pMDI or Aerolizer) in Moderate to Severe Asthmatic Patients
Authors: Bousquet J. , Guenolé E. , Duvauchelle T. , Vicaut E. , Lefrançois G.
Published: May 2005

Background: Chlorofluorocarbons (CFCs) have traditionally been used as propellants in pressurized metered-dose inhalers (pMDIs), which are often used to deliver drugs to the lungs for the treatment of reversible obstructive airways diseases. However, CFCs are harmful to the environment and need to be phased out. In response to that phase-out of environmentally harmful CFCs, the pharmaceutical industry is developing a new generation of pMDI formulations for the inhaled treatment of asthma. These formulations contain hydrofluoroalkanes (HFAs) in redesigned metered-dose inhalers. Objectives: This study primarily sought to establish clinical equivalence between a new HFA-formulated formoterol pMDI and the conventional formoterol DPI in the treatment of patients with moderate-to-severe asthma. Methods: We enrolled 51 patients aged 18–70 years old who had stable persistent asthma. All patients were randomized to receive a single dose of each of the following 4 treatments in a double-blind, crossover manner: formoterol HFA pMDI 24 µg, formoterol HFA pMDI 12 µg, formoterol DPI 24 µg or placebo. Results: Of the 51 patients randomised, 46 were evaluable for efficacy. The 12-hour average FEV1 was 2.885, 2.746, 2.916 and 2.353 liters in the HFA 24-µg, HFA 12-µg, DPI 24-µg and placebo groups, respectively. Assessment of 95% CIs revealed that the HFA pMDI 24-µg and DPI formulations were equivalent and that both were significantly superior to placebo (p < 0.001). Improvements in lung function were also significantly superior to placebo in the HFA 12-µg group, but the effect was more moderate than that observed in the higher dose groups. Conclusions: This study indicates that the formoterol HFA-formulated pMDI provides equivalent bronchodilating effect to the formoterol DPI at the 24-µg dose.
Double-Blind, Double-Dummy, Multinational, Multicenter, Parallel-Group Design Clinical Trial of Clinical Non-Inferiority of Formoterol 12 μg/Unit Dose in a b.i.d. Regimen Administered via an HFA-Propellant-pMDI or a Dry Powder Inhaler in a 12-Week Treatment Period of Moderate to Severe Stable Persistent Asthma in Adult Patients
Authors: Dusser D. , Vicaut E. , Lefrançois G.
Published: May 2005

Background: Pressurized metered-dose inhalers (pMDIs) have traditionally used CFCs as propellants. However, the worldwide phase-out of CFCs has necessitated the development of new pMDIs that use alternative propellants. One such replacement is the hydrofluoroalkane HFA-134a. Objectives: This study sought to establish the clinical non-inferiority of a new HFA-134a-containing pMDI to a conventional dry powder inhaler (DPI) in the administration of formoterol to adult patients with moderate-to-severe, stable persistent asthma. The secondary aim was to collect safety data in a multiple-dose long-term study. Methods: During this multicenter, double-blind, parallel study, 500 patients were randomized to receive 12 µg of formoterol twice daily for 12 weeks via either an HFA pMDI or a DPI. If necessary, the dose could be increased to 24 µg twice daily. At baseline, all patients (aged 18–70 years) had an FEV1 40–80% of predicted and a documented positive response to the reversibility test. Results: After 12 weeks’ therapy, the adjusted mean morning PEFR was 343.69 l/min in the formoterol HFA pMDI group and 344.56 l/min in the formoterol DPI group. Because the lower limit of the 95% CI for the between-group difference (–11.64 l/min) was well within the non-inferiority margin (–20 l/min), the HFA device was deemed clinically non-inferior to the DPI device. This finding was confirmed when evening PEFR and FEV1 were assessed. Both formulations of formoterol were well tolerated during prolonged multiple dosing. Conclusions: This study provides evidence that the new HFA-formulated formoterol pMDI has a similar efficacy and safety profile to the conventional formoterol DPI in the treatment of patients with moderate-to-severe asthma.
Is There an Association between Low Birth Weight and Caries in the Primary Dentition?
Authors: Shulman J.D.
Published: May 2005

Objectives: An association between low birth weight and caries in the primary dentition has been suggested but not demonstrated. This study analyzed this association using data from a probability sample of US children 2–6 years of age. Methods: Data from the Third National Health and Nutrition Examination Survey (NHANES III) were used. Variables included decayed and filled primary surfaces (dfs), birth weight, gestational age, and Apgar score (a surrogate measure of fetal well-being); maternal age, education, income; number of previous births, marital status, the existence of pregnancy complications, and cigarette smoking during the pregnancy. Data were analyzed using SUDAAN 8.0.2. Results: Bivariate Poisson regression showed that children of mothers who were unmarried (incidence density ratio, IDR = 3.28), with less education (IDR = 1.43), who were 17 years of age or younger at birth (IDR = 1.51), and had 2 or fewer prenatal visits (IDR = 1.65) had a significantly ( p <0.05) greater risk of caries than the reference groups. Children of mothers with pregnancy-related hypertension (IDR = 0.14) had less than 20% the risk of caries than the reference group. Blacks (IDR = 1.37) and Mexican-Americans (IDR = 2.38) had greater risk of caries than whites, and children of low (IDR = 2.57) and middle income (IDR = 2.00) level families had higher caries risks than those of upper income families. Multivariate Poisson regression found only race-ethnicity, age, and income level to be statistically significant. Conclusions: This study did not support the association between low birth weight and caries of the primary dentition.
Dental Caries and Microbial Acid Production in Twins
Authors: Bretz W.A. , Corby P.M.A. , Hart T.C. , Costa S. , Coelho M.Q. , Weyant R.J. , Robinson M. , Schork N.J.
Published: May 2005

Objective: To determine the relative contribution of genetic and environmental stimuli on dental caries traits and microbial acid production in a twin model. Methods: Dental caries examinations and microbial acid production assays were performed on 388 pairs of twins 1.5–8 years old from the city of Montes Claros, Brazil. Genotyping 8 polymorphic DNA markers determined zygosity. Caries exams followed NIDCR criteria modified to distinguish white spot lesions from cavitated lesions. Surface-based caries prevalence rates (SBCPR) were computed and lesion severity was determined by a weighted index (LSI). Biofilm samples were collected from the tongue using a lactic acid indicator swab. Assay scores were categorized based on acid formation as 1 = low, 2 = medium, and 3 = high. Heritability analyses were performed using the SOLAR software package. Results: Heritability estimates for SBCPRs, LSI and for microbial acid production were H = 76.3 (p < 0.001), H = 70.6 (p < 0.001), H = 16.2 (p = 0.0078), respectively. Treating microbial acid production as a covariate in the SBCPR and LSI models did not significantly alter the heritability estimates, i.e. H = 76.5 (p < 0.001) and H = 70.8 (p < 0.001), respectively. Conclusions: These results suggest that variation in dental caries surface traits has a significant genetic contribution and that microbial acid production is modulated by the environment.
Visual and Tactile Assessment of Arrested Initial Enamel Carious Lesions: An in vivo Pilot Study
Authors: Ekstrand K.R. , Ricketts D.N.J. , Longbottom C. , Pitts N.B.
Published: May 2005

Accurate and reliable assessment of caries activity is important for determining appropriate treatment needs. The aim of this pilot study was to determine whether dentists could differentiate between the appearances (visual and tactile) of lesions inactivated by regular professional oral hygiene and those control lesions which were not cleaned (active). After a 3- to 4-week study period involving 10 children, with 4 similar carious lesions each, it was found that dentists were not able to reliably and reproducibly determine the subtle visual and tactile differences between active and inactive enamel lesions from a one-off clinical examination.
Comparison of Calcium/Phosphorus Analysis, Longitudinal Microradiography and Profilometry for the Quantitative Assessment of Erosive Demineralisation
Authors: Ganss C. , Lussi A. , Klimek J.
Published: May 2005

The study is a comparison of methods for the quantitative measurement of erosive mineral loss including longitudinal microradiography (LMR), profilometry (PM), and analysis of calcium (CA) and phosphorus (PA) in the erosion solution. Polished human enamel samples were taped, covered with nail varnish and the edges of the resulting enamel window marked with drilled holes as a reference. All samples were subjected to baseline LMR. Sixty samples each were eroded with citric acid (0.05 M; pH 2.3; 10 ml per sample) for 30, 60, 90, or 120 min. Erosive loss of each sample was estimated by the four methods. All methods revealed a linear erosive loss over time and showed good linear correlation. Values calculated from PM and LMR were both approximately 20% lower than those from CA and PA. After 30 min erosion, LMR showed no significant correlation with the other three methods. With LMR, erosive loss below 20 µm should be interpreted with care.
A Novel in vitro Microbial-Based Model for Studying Caries Formation – Development and Initial Testing
Authors: Seemann R. , Bizhang M. , Klück I. , Loth J. , Roulet J.-F.
Published: May 2005

We report on the development and the initial testing of a new microbial-based caries model. Specimens were fixed on a rotating mount within a reaction chamber hermetically surrounded by a sterilised glove box. A cariogenic environment was obtained by inoculation with Streptococcus mutans (ATCC 25175) combined with a continuously repeating supply of sucrose solution, trypticase soy broth and artificial saliva applied by dripping. Twenty-five caries-free upper premolars were used. The mesial parts of the occlusal fissures had been sealed with a resin-based fissure sealant (test group 1). To produce marginal gaps, the distal parts had been moistened with saliva before resin application (test group 2). Five teeth served as control and were exposed to all fluids under sterile conditions before being removed from the system after 7 days. Test specimens were infected with S. mutans and were incubated for another 14 days. No unintentional contamination occurred during the 3-week period of operation. Demineralizations were evaluated by using confocal laser scanning microscopy. Only the test specimens showed clearly visible signs of biofilm formation and caries-like lesions. The mean primary lesion depth did not differ significantly between test groups. Wall lesion depths and surface areas of demineralizations underneath the fissure sealants were significantly higher in test group 2. Thus, our model allows the simultaneous production of primary and secondary caries-like enamel lesions in a considerable number of specimens and facilitates the possibility to manipulate and transfer them without necessarily terminating the experiment, opening new possibilities for in vitro caries research.
Evaluation of a New Intraoral Controlled Fluoride Release Device
Authors: Altinova Y.B. , Alaçam A. , Aydin A. , Sanisoglu S.Y.
Published: May 2005

The aim of the study was to determine the pharmacokinetics of a new hydroxyapatite-Eudragit RS100 diffusion-controlled fluoride-releasing system designed for intraoral use with a 0.15 mg F–/day release for a 1-month period. Matrix tablets, each containing 18 mg of sodium fluoride, were bonded to the buccal surface of the first maxillary molar teeth of 20 subjects (age 20–23 years). Morning and evening salivary and urinary samples were collected 5 days before the study and every day for the 1st week, then once a week for 1 month. Fluoride ion measurements were done using the microdiffusion method. The salivary and urinary fluoride concentrations were significantly raised during the treatment period (p < 0.05). Morning salivary fluoride levels were higher than evening salivary fluoride levels (p < 0.05) whereas evening urinary fluoride levels were higher than morning urinary fluoride levels (p < 0.05). The statistically significant increase in salivary fluoride levels indicates a caries-preventive role for this device.
A Clinical Trial of a Slow-Releasing Fluoride Device in Children
Authors: Toumba K.J. , Curzon M.E.J.
Published: May 2005

The objective was to test a fluoride-containing slow-release device in preventing dental caries in children. Accordingly a population of 174 children aged 8 years living in a high-caries, low socio-economic area of Leeds (UK) was assembled. Two slow-release/dissolving glass (SFG) pellets, one with fluoride (F) and one without, were randomly attached to the maxillary molars of the children. Baseline caries as dmft/s, DMFT/S, periodontal disease, plaque and calculus were recorded using standard indices. Unstimulated saliva samples were collected 2 h postprandial for F analysis. All parameters were measured at 6-month intervals for 2 years. There were 132 children completing the trial of whom 63 (test n = 31, control n = 32) still retained the glass devices at the end. Comparison of mean values for gingival health and calculus showed no differences between groups throughout the trial. Mean caries as dmfs at the end of the trial (2.26) was significantly lower for the test (SFG, 2.26) compared with that for the control children (8.41; p ≤ 0.001). DMFS was significantly lower at 0.84 and 2.34, respectively (p ≤ 0.05). Mean salivary fluoride concentrations were 0.11 and 0.03 mg/l for test and control groups. It was concluded that placement of a glass slow-releasing fluoride device significantly reduced caries incidence in a group of low socio-economic schoolchildren over 2 years.
Effect of a Hydroxyl Ion-Releasing Composite Resin on Plaque Acidogenicity
Authors: Persson A. , Lingström P. , van Dijken J.W.V.
Published: May 2005

The aim of this in vivo study was to evaluate the neutralizing capacity, registered as change of plaque acidogenicity, on aged proximal restorations of an ion-releasing composite resin (IRCR), which releases hydroxyl, calcium, and fluoride ions at low pH. Twenty patients, with a mean age of 63 years (range 43–85), participated. All had one aged proximal IRCR restoration (mean age 15 months) and one nonrestored enamel surface to make an intraindividual comparison possible. The neutralizing effect of the IRCR was evaluated by measuring plaque pH, using the microtouch method, after a mouthrinse with 10% sucrose. The plaque pH measurements were repeated 1.5 years later on the IRCR (mean age 34 months), the enamel surfaces and a universal hybrid composite resin (CR). At both 15 and 34 months, the plaque on the IRCR surfaces showed the least acidogenic potential for the whole 60-min time interval. The largest differences between the IRCR, CR and enamel were found during the first 15 min. At 15 months, the total areas under the plaque pH curve (AUC5.7 and AUC6.2) differed significantly between the IRCR and enamel surfaces for the time periods 0–5 min and 5–15 min. At 34 months, significant differences were found between IRCR and CR at the 0- to 5-min time period. It can be concluded that IRCR restorations countered the plaque pH fall and maintained it at levels where less enamel and dentin demineralization can occur.
Similarity of the Effects ofErythritol and Xylitol on SomeRisk Factors of Dental Caries
Authors: Mäkinen K.K. , Saag M. , Isotupa K.P. , Olak J. , Nõmmela R. , Söderling E. , Mäkinen P.-L.
Published: May 2005

Several sugar alcohols (polyols) have been promoted as potential sugar substitutes in caries limitation. However, differences in the effects of simple alditol-type sugar alcohol homologues on dental plaque have not been compared in clinical tests. The effects of 6-month use of erythritol (a sugar alcohol of the tetritol type), xylitol (a pentitol) and D-glucitol (sorbitol, a hexitol) were investigated in a cohort of 136 teenage subjects assigned to the respective polyol groups or to an untreated control group (n = 30–36 per group). The daily use of the polyols was 7.0 g in the form of chewable tablets, supplemented by twice-a-day use of a dentifrice containing those polyols. The use of erythritol and xylitol was associated with a statistically significant reduction (p < 0.001 in most cases) in the plaque and saliva levels of mutans streptococci. The amount of dental plaque was also significantly reduced in subjects receiving erythritol and xylitol. Such effects were not observed in other experimental groups. Chemical analyses showed D-glucitol to be a normal finding in dental plaque while xylitol was less consistently detected. Erythritol was detected in measurable amounts only in the plaque of subjects receiving this polyol. Erythritol and xylitol may exert similar effects on some risk factors of dental caries, although the biochemical mechanism of the effects may differ. These in vivo studies were supported by cultivation experiments in which xylitol, and especially erythritol, inhibited the growth of several strains of mutans streptococci.
Caries-Preventive Agents Induce Remineralization of Dentin in a Biofilm Model
Authors: Deng D.M. , van Maele C. , ten Cate J.M.
Published: May 2005

The aim was to study remineralization in dentin underneath a biofilm. This was done in a constant depth film fermentor (CDFF) which was modified so that two treatments can be applied simultaneously in one experiment. Forty-five Streptococcus mutans biofilms were grown in grooves in dentin. Growth medium (3.7 g/l BHI, 1.5 mM calcium and 25 mM PIPES) was administered alternately with 2% sucrose pulsing 4 × 30 min/day. Fluoride at 135 ppm as NaF only or in a mixture with 0.2% chlorhexidine was applied for 2 × 5 min/day. The treatments started 5 days after inoculation and lasted 15 days. Five specimens per group were removed at various time points. The biofilms were checked for viability (by plating) and acid content (by capillary electrophoresis). The dentin specimens were analysed for mineral loss and lesion depth (by transversal microradiography). Fluoride treatment had no effect on the viability but reduced lactic acid production by 75%. The mixture treatment reduced the viability by 80% and the lactic acid content by 93% on the first day and later reduced the two parameters to below the detection limits. Significant differences in changes in mineral loss and lesion depth were observed between the treatment groups. Partial remineralization but deeper lesions were observed in the fluoride group, while nearly complete remineralization was seen in the mixture group. In conclusion, the CDFF S. mutans biofilm model can be used as a de- and remineralization biofilm model, and the split mode is particularly suitable for testing caries-preventive agents.
Total and Free Fluoride in Toothpastes from Some Non-Established Market Economy Countries
Authors: van Loveren C. , Moorer W.R. , Buijs M.J. , van Palenstein Helderman W.H.
Published: May 2005

In 101 fluoride toothpastes, bought in local shops in Burkina Faso (n = 3), China (n = 5), Myanmar (n = 22), Nepal (n = 19), Philippines (n = 13), Syria (n = 22), Togo (n = 7) and Vietnam (n = 10), the total and free ionisable fluoride concentrations were established. The total fluoride concentration of the toothpastes was determined by gas liquid chromatography. The amount of soluble fluoride was measured after dilution in artificial saliva and treatment of the supernatants with acidic phosphatase. The free fluoride concentration in this mixture was measured with a fluoride electrode. Twenty-five percent of all toothpastes contained less than 738 ppm total fluoride, and another 25% contained between 738 and 977 ppm fluoride. Regarding free ionisable fluoride the 25th, 50th, and 75th percentile contained ≤275, 780 and 990 ppm fluoride, respectively. Of the 61 toothpastes with declared fluoride concentration, 75% contained a total F concentration of ≧89% of the declared concentration. In 25% of these toothpastes the free ionisable fluoride was ≤55% of the declared fluoride, and in another 25% of the pastes the free ionisable fluoride concentration was ≧89% of the declared fluoride. In conclusion, deficiencies were found regarding the total as well as the free ionisable fluoride concentration of toothpastes bought in non-established market economy countries. Unclear labelling concerning the type and concentration of fluoride was often encountered. A need for quality control of fluoride toothpastes is recommended.
Caries Prevention by Professional Fluoride Gel Application on Enamel and Dentinal Lesions in Low-Caries Children
Authors: Truin G.J. , van’t Hof M.A.
Published: May 2005

In a double-blind randomized controlled clinical trial, the caries-reducing effect of semi-annually applied fluoride gel in a low-caries child population initially aged 4.5–6.5 years (n = 773) has been investigated. Secondary analyses of the data were performed to study the caries reduction including non-cavitated lesions. The treatment effect of fluoride gel was calculated as preventive fraction (PF). When enamel lesions were included in DFS count (D2 grade), the PF was 22% as compared to 26% counting dentinal lesions. The PFs showed that the mean effect of professionally applied fluoride gel was highest (71%) for D3S in the permanent dentition and lowest for d3s in the primary dentition (5%). The PFs for approximal and buccal and lingual surfaces of the permanent dentition significantly decreased from 80 to 25% and from 60 to 37% when enamel lesions (D2S) were included. With the exception of the buccal and lingual surfaces, in the primary dentition the PFs varied slightly when enamel lesions were included. Inclusion of non-cavitated lesions in the treatment effect statistics did not change the former conclusion that the treatment effect of fluoride gel application on dental caries reduction in a low-caries child population was considered not clinically relevant.
Clinical Trial of a Plant-Derived Antibody on Recolonization of Mutans Streptococci
Authors: Weintraub J.A. , Hilton J.F. , White J.M. , Hoover C.I. , Wycoff K.L. , Yu L. , Larrick J.W. , Featherstone J.D.B.
Published: May 2005

Objective: This double-blinded, placebo-controlled clinical trial tested the safety and efficacy of a topical secretory IgA antibody manufactured in tobacco plants (plantibody) in preventing recolonization of mutans streptococci (MS) in human plaque as measured by whole stimulated saliva samples. Methods: Following a 9-day antimicrobial treatment with chlorhexidine (CHX), 56 eligible adults (enrollment salivary MS ≧ 104 CFU/ml; no current caries) were randomized equally to a group receiving 0, 2, 4, or 6 topical applications of plantibody followed by 6, 4, 2, or 0 applications of placebo, respectively, over a 3-week period. Results: Among the 54 subjects who completed the trial, the CHX regimen eliminated salivary MS in 69%. After 6 months, there were no significant differences in MS levels by number of applications, relative to placebo (p > 0.43). No adverse effects were observed. Conclusion: Plantibody is safe but not effective at the frequency, concentration, and number of applications used in this study.
Long-Term Outcome of Patients with Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis with Renal Involvement
Authors: Rihova Zuzana , Jancova Eva , Merta Miroslav , Rysava Romana , Reiterova Jana , Zabka Jiri , Tesař Vladimir
Published: May 2005

Background: Despite treatment, renal involvement in antineutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis is still associated with significant long-term mortality and remains an important cause of end-stage renal failure. Methods: We retrospectively analyzed a series of 61 consecutive patients with newly diagnosed ANCA-associated renal vasculitis (54.1% Wegener’s granulomatosis, 23% renal-limited vasculitis, 16.4% microscopic polyangiitis, 4.9% Churg-Strauss syndrome) diagnosed between 1986 and 1997. Results: The median creatinine level at diagnosis was 221.5 (63–762) µmol/l, i.e. 2.5 (0.7–8.6) mg/dl, 32.8% were dialysis-dependent. All patients were treated with cyclophosphamide. Remission was achieved in 87% of patients. Relapses occurred in 44.7%. The median renal disease-free interval was 62.5 (0–138) months. The estimated patient survival at 5 and 10 years was 78.3 and 62.2%, respectively. Mortality was associated with age (p = 0.04 when age limit 50 years) and advanced renal failure (p = 0.038 when compared dialysis-dependent and independent patients). Estimated renal survival time at 5 and 10 years was 69.2 and 55.8%, respectively. At the end of follow-up, 50.8% of patients were in complete remission, 31% had died. The median serum creatinine level was 137.5 (77–469) µmol/l, i.e. 1.56 (0.87–5.3) mg/dl, 24.6% of patients were on regular dialysis treatment. Conclusion: Patient survival, relapse rate and mortality were comparable to similar reports. In view of the severity of the renal disease and the length of follow-up, renal survival was very good. Despite effective treatment, the long-term outcome of patients with ANCA-associated renal vasculitis remains unsatisfactory.
Hyperhomocysteinemia Is Associated with Lower Performance on Memory Tasks in Post-Menopausal Women
Authors: Clark Margaret S. , Guthrie Janet R. , Dennerstein Lorraine
Published: May 2005

Increased levels of total homocysteine (tHcy) have been associated with lower performance on tests of cognitive function, and may be a potential preclinical marker for Alzheimer’s disease. Most reports have focused on older cohorts, but raised tHcy levels, in association with cognitive changes may be occurring in earlier years. Scores for verbal and working memory were compared to plasma homocysteine levels for 200 healthy women aged 56–67 (mean = 60). Smoking, hormone therapy and age were significantly associated with increased levels of tHcy, whilst vitamin B or folate supplements were significantly associated with lower tHcy levels. Hyperhomocysteinemia (>13 µmol/l) was significantly associated with poor performance for combined verbal and working memory, and there was a trend for hyperhomocysteinemia to be associated with the learning trials for 2 word lists, but not for the delayed trial. As hyperhomocysteinemia is associated with memory changes in women aged 56–67, it may be playing a role in the early dementia processes.
Diagnostic Value of FDG-PET and HMPAO-SPET in Patients with Mild Dementia and Mild Cognitive Impairment: Metabolic Index and Perfusion Index
Authors: Döbert Natascha , Pantel Johannes , Frölich Lutz , Hamscho Nadja , Menzel Christian , Grünwald Frank
Published: May 2005

Objective: The diagnostic potential of F-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (PET) and technetium-99m hexamethylpropylene amine oxime single-photon emission tomography (SPET) in early detection and differential diagnosis of early dementia was evaluated including a comparison of metabolic and perfusion indices (PI). Methods: Twenty-four patients with initial clinical suspicion of beginning dementia were examined, 12 of them with mild cognitive impairment. All patients underwent SPET and PET within 2 weeks. Data were compared with the final clinical diagnosis at follow-up – 9 with Alzheimer’s disease (AD), 1 with frontotemporal dementia, 1 with vascular dementia (VD), 7 with mixed type of dementia (MIX) and 6 without any type of dementia. Metabolic indices (MI) and PI were compared with each other. The regional cerebral blood flow difference (rCBFdiff) calculated as local uptake difference between the right and left hemisphere was measured for patients with VD and MIX. Results: PET showed higher sensitivity and specificity in identifying the different types of early dementia (44–91 and 78–89%, respectively) than SPET (11–64 and 79–89%, respectively), especially in detecting AD (sensitivity 44%, specificity 83%) and MIX (sensitivity 71%, specificity 78%). Especially in patients with mild cognitive impairment, PET was the superior imaging modality for predicting dementia. Using PET, dementia could be excluded in all patients who did not develop dementia during the follow-up. In all patients, a weak correlation between PI and MI was observed (rho = 0.64, p < 0.002). The rCBFdiff in patients with VD and MIX ranged from 7 to 37%. Conclusion: In this study on patients with initial suspicion of beginning dementia who underwent both imaging modalities, PET and SPET, PET was the superior imaging method, especially in the detection of early AD or MIX.
Association between Cognitive Impairment and Gait Disturbance in Patients with Idiopathic Normal Pressure Hydrocephalus
Authors: Miyoshi Noriko , Kazui Hiroaki , Ogino Atsushi , Ishikawa Masatsune , Miyake Hiroji , Tokunaga Hiromasa , Ikejiri Yoshitaka , Takeda Masatoshi
Published: May 2005

We compared the scores of the Frontal Assessment Battery (FAB), initial fluency subtest, category fluency subtest and subtests of the Mini-Mental State Examination (MMSE) between patients with idiopathic normal pressure hydrocephalus (iNPH) and age-, sex- and MMSE-matched patients with Alzheimer’s disease (AD). In patients with iNPH, the time and number of steps required to go and come back a 10-meter distance were measured (Walking test) and the associations between the scores of the cognitive tests and the performance of the Walking test were evaluated. The scores of the FAB and initial fluency subtest in patients with iNPH were significantly lower than those in patients with AD. The scores of the FAB, initial fluency subtest and serial 7 subtest of the MMSE significantly correlated with the two scores of the Walking test in patients with iNPH. The present results indicate that frontal lobe functions were impaired in patients with iNPH and that cognitive impairment was closely associated with gait disturbance in patients with iNPH.
Depressive Symptoms Predict Slow Cognitive Decline in Mild Dementia
Authors: Janzing J.G.E. , Naarding P. , Eling P.
Published: May 2005

Depression may be a prognostic marker of subsequent cognitive decline in patients with dementia. Earlier investigations did not find support for this hypothesis, but these considered mainly syndromal depression. In this prospective study, 32 subjects with mild dementia were followed up for 12 months. The effects of GMS-AGECAT syndromal depression, subsyndromal depression and dimensions of depressive symptoms were studied. Higher levels of mood symptoms but not (sub)syndromal depression predicted slower cognitive decline during follow-up. It is hypothesized that the report of depressive symptoms by subjects with mild dementia reflects relative intactness of cognitive functions, not accounted for by cognitive screening instruments.
Skin Metabolism in Transdermal Therapeutic Systems
Authors: Hikima T. , Tojo K. , Maibach H.I.
Published: May 2005

Skin has at least two barriers with protective functions: the stratum corneum physical barrier and a biochemical barrier in the epidermis and dermis. Numerous chemical and physical enhancers exist for transdermal therapeutic systems; some cause irritation, and possibly influence enzyme deactivation. Knowledge of enzymatic skin reactions is important for developing safe and efficacious transdermal systems for treatment not only of skin diseases but also for systemic application. This paper overviews the effects of (a) chemical enhancers and additives, (b) drug structure, and (c) physical enhancement on skin metabolism.
Sunscreen Penetration of Human Skin and Related Keratinocyte Toxicity after Topical Application
Authors: Hayden C.G.J. , Cross S.E. , Anderson C. , Saunders N.A. , Roberts M.S.
Published: May 2005

Sunscreen skin penetration and safety assessment should be considered together in order to ensure that in vitro cytotoxicity studies examine relevant doses of these organic chemical UV filters to which viable epidermal cells are realistically exposed. In this study, we sought to determine whether sufficient topically applied sunscreens penetrated into human viable epidermis to put the local keratinocyte cell populations at risk of toxicity. The penetration and retention of five commonly used sunscreen agents (avobenzone, octinoxate, octocrylene, oxybenzone and padimate O) in human skin was evaluated after application in mineral oil to isolated human epidermal membranes. Sunscreen concentration–human keratinocyte culture response curves were then defined using changes in cell morphology and proliferation (DNA synthesis using radiolabelled thymidine uptake studies) as evidence of sunscreens causing toxicity. Following 24 h of human epidermal exposure to sunscreens, detectable amounts of all sunscreens were present in the stratum corneum and viable epidermis, with epidermal penetration most evident with oxybenzone. The concentrations of each sunscreen found in human viable epidermis after topical application, adjusting for skin partitioning and binding effects, were at least 5-fold lower, based on levels detected in viable epidermal cells, than those appearing to cause toxicity in cultured human keratinocytes. It is concluded that the human viable epidermal levels of sunscreens are too low to cause any significant toxicity to the underlying human keratinocytes.
The Number of Stratum corneum Cell Layers Correlates with the Pseudo-Absorption of the Corneocytes
Authors: Jacobi U. , Kaiser M. , Richter H. , Audring H. , Sterry W. , Lademann J.
Published: May 2005

The removal of the stratum corneum (SC) using adhesive tapes is a common technique in cutaneous studies. The determination of the varying amounts of the SC removed would be a helpful tool in such investigations. In the present study, the cell layers of porcine SC were counted before and after removal of several tape strips using histological techniques. In addition, the pseudo-absorption of the corneocytes reflecting the amount of these cells was determined using spectroscopy. Different amounts of SC were removed using 20 tape strips. The spectroscopically determined data correlate linearly with the number of removed cell layers. Based on these results, the pseudo-absorption of the corneocytes can be used to calculate the absolute number of cell layers removed with a standard deviation of less than 11%. In this way, the SC can be quantified using the procedure of tape stripping in combination with the spectroscopic determination of the corneocytes.