The Pharmacokinetic Exposure to Fexofenadine is Volume-Dependently Reduced in Healthy Subjects Following Oral Administration With Apple Juice.

Pharmacokinetic exposures to fexofenadine (FEX) are reduced by apple juice (AJ); however, the relationship between the AJ volume and the degree of AJ-FEX interaction has not been understood. In this crossover study, 10 healthy subjects received single doses of FEX 60 mg with different volumes (150, 300, and 600 mL) of AJ or water (control). To identify an AJ volume lacking clinically meaningful interaction, we tested a hypothesis that the 90% confidence interval (CI) for geometric mean ratio (GMR) of FEX AUCAJ /AUCwater is contained within a biocomparability bound of 0.5-2.0, with at least one tested volume of AJ. GMR (90% CI) of AUCAJ 150mL /AUCwater , AUCAJ 300mL /AUCwater , and AUCAJ 600mL /AUCwater were 0.903 (0.752-1.085), 0.593 (0.494-0.712), and 0.385 (0.321-0.462), respectively. While a moderate to large AJ-FEX interaction is caused by a larger volumes of AJ (e.g., 300 to 600 mL), the effect of a small volume (e.g., 150 mL) appears to be not meaningful.

3-T MRI safety assessments of magnetic dental attachments and castable magnetic alloys.

OBJECTIVES: To assess the safety of different magnetic dental attachments during 3-T MRI according to the American Society for Testing and Materials F2182-09 and F2052-06e1 standard testing methods and to develop a method to determine MRI compatibility by measuring magnetically induced torque. METHODS: The temperature elevations, magnetically induced forces and torques of a ferromagnetic stainless steel keeper, a coping comprising a keeper and a cast magnetic alloy coping were measured on MRI systems. RESULTS: The coping comprising a keeper demonstrated the maximum temperature increase (1.42 °C) for the whole-body-averaged specific absorption rate and was calculated as 2.1 W kg⁻¹ with the saline phantom. All deflection angles exceeded 45°. The cast magnetic alloy coping had the greatest deflection force (0.33 N) during 3-T MRI and torque (1.015 mN m) during 0.3-T MRI. CONCLUSIONS: The tested devices showed minimal radiofrequency (RF)-induced heating in a 3-T MR environment, but the cast magnetic alloy coping showed a magnetically induced deflection force and torque approximately eight times that of the keepers. For safety, magnetic dental attachments should be inspected before and after MRI and large prostheses containing cast magnetic alloy should be removed. Although magnetic dental attachments may pose no great risk of RF-induced heating or magnetically induced torque during 3-T MRI, their magnetically induced deflection forces tended to exceed acceptable limits. Therefore, the inspection of such devices before and after MRI is important for patient safety.

Positions of pluripotency genes and hepatocyte-specific genes in the nucleus before and after mouse ES cell differentiation.

Spatial positioning of genes in the cell nucleus plays an important role in the regulation of genomic functions. Evidence for changes in gene positioning associated with transcriptional activity has been reported. However, our understanding of this phenomenon is still quite limited. We examined how pluripotency genes and hepatocyte-specific genes behave during the differentiation of mouse embryonic stem (ES) cells into hepatocytes, by targeting the loci of the Klf4, Nanog, Oct4, Sox2, Cyp7α1, Pck1, Tat, and Tdo2 genes, and using three-dimensional fluorescence in situ hybridization analyses. We found that each gene has a distinctly inherent localization profile in the ES cell nucleus. During differentiation, the Klf4, Nanog, Oct4, Cyp7α1, Pck1, and Tat loci shifted toward the nuclear center, while the Sox2 and Tdo2 loci shifted toward the periphery. The Klf4, Nanog, Oct4, and Tdo2 seem to prefer the outer regions, rather than the inner regions, when they are active. We also found that the radial positioning of the focused genes in the hepatocyte cell nucleus was highly correlated with the local GC content and the gene density of the surrounding region, but not with gene activity.

A designed curved DNA sequence remarkably enhances transgene expression from plasmid DNA in mouse liver.

The intranuclear disposition of plasmid DNA is extremely important for transgene expression. The interactions between the plasmid DNA and the histone proteins are one of the keys for controlling the disposition. In this study, the effects of a left-handedly curved sequence (20-40 repeated A•T tracts) on transgene expression from a plasmid were examined in vivo. A naked luciferase plasmid with the curved sequence was delivered into mouse liver by a hydrodynamics-based injection, and the luciferase activities were quantitated at various time points. Interestingly, transgene expression was markedly increased by the addition of the curved sequence. An analysis of the nucleosome positions near the left-handedly curved sequence suggested that the sequence functions as an acceptor of the histone core and allows nucleosome sliding, resulting in transcriptional activation. These results suggested that the designed curved DNA sequences could control transgene expression from plasmid DNAs in vivo.

Azelnidipine is a calcium blocker that attenuates liver fibrosis and may increase antioxidant defence.

BACKGROUND AND PURPOSE: Oxidative stress plays a critical role in liver fibrogenesis. Reactive oxygen species (ROS) stimulate hepatic stellate cells (HSCs), and ROS-mediated increases in calcium influx further increase ROS production. Azelnidipine is a calcium blocker that has been shown to have antioxidant effects in endothelial cells and cardiomyocytes. Therefore, we evaluated the anti-fibrotic and antioxidative effects of azelnidipine on liver fibrosis. EXPERIMENTAL APPROACH: We used TGF-ß1-activated LX-2 cells (a human HSC line) and mouse models of fibrosis induced by treatment with either carbon tetrachloride (CCl(4) ) or thioacetamide (TAA). KEY RESULTS: Azelnidipine inhibited TGF-ß1 and angiotensin II (Ang II)-activated α1(I) collagen mRNA expression in HSCs. Furthermore, TGF-ß1- and Ang II-induced oxidative stress and TGF-ß1-induced p38 and JNK phosphorylation were reduced in HSCs treated with azelnidipine. Azelnidipine significantly decreased inflammatory cell infiltration, pro-fibrotic gene expressions, HSC activation, lipid peroxidation, oxidative DNA damage and fibrosis in the livers of CCl(4) - or TAA-treated mice. Finally, azelnidipine prevented a decrease in the expression of some antioxidant enzymes and accelerated regression of liver fibrosis in CCl(4) -treated mice. CONCLUSIONS AND IMPLICATIONS: Azelnidipine inhibited TGF-ß1- and Ang II-induced HSC activation in vitro and attenuated CCl(4) - and TAA-induced liver fibrosis, and it accelerated regression of CCl(4) -induced liver fibrosis in mice. The anti-fibrotic mechanism of azelnidipine against CCl(4) -induced liver fibrosis in mice may have been due an increased level of antioxidant defence. As azelnidipine is widely used in clinical practice without serious adverse effects, it may provide an effective new strategy for anti-fibrotic therapy.

Assimilation and translocation of nitrogen and carbon in Curcuma alismatifolia Gagnep.

Curcuma or Siam tulip (Curcuma alismatifolia Gagnep.) is an ornamental flowering plant with two underground storage organs, rhizomes and storage roots. Characteristics of N and C assimilation and transport in curcuma were investigated. The plants were treated with (15)NH(4) (+) + (15)NO(3) (-) and (13)CO(2) at 10, 13 or 21 weeks after planting. Plants were sampled at several stages up to 32 weeks. The C stored in old storage roots was used rapidly during the first 10 weeks; after which N stored in old rhizomes and old storage roots were used. The daily gain in C depending on photosynthesis was remarkably high between 10 and 21 weeks. However, the daily gain in N was relatively constant throughout the growth period. The (15)N absorbed at 10 weeks was initially accumulated in leaves and roots, but some was transported to flowering organs at 13 weeks. At harvest, 41% of (15)N was recovered in new rhizomes and 17% in new storage roots. After (13)CO(2) exposure at 10 and 13 weeks, the distribution of (13)C among organs was relatively constant in subsequent stages. When given (13)CO(2) at 21 weeks, a large amount of labelled C was recovered in new storage roots and new rhizomes at harvest. Both new rhizomes and new storage roots stored N and C, however, rhizomes played a more important role in supplying N, while storage roots provided C.

An outbreak of psittacosis in a bird park in Japan.

An outbreak of psittacosis related to a bird park occurred in Matsue City, Shimane Prefecture, Japan, during winter 2001. Seventeen cases of psittacosis (12 visitors, three staff, and two student interns) were confirmed. A cohort study was conducted among the park staff and students to determine the risk factors for the development of acute serologically confirmed psittacosis (SCP) infection. Being 'bird staff' had an increased risk of SCP infection (RR 3.96, 95% CI 1.48-10.58). Entering the staff building, where ill birds were maintained without proper isolation, was also associated with an increased risk of SCP infection (RR 3.61, 95% CI 1.03-12.6). Isolation of ill birds and quarantine measures were found to be insufficient. Dehumidifiers and a high-pressure water spray under a closed ventilation environment may have raised the concentration of Chlamydophila psittaci in the hothouses. Bird park staff and visitors should be educated about psittacosis.

Objective and subjective hardness of a test item used for evaluating food mixing ability.

The aim of this study was to compare objective and subjective hardness of selected common foods with a wax cube used as a test item in a mixing ability test. Objective hardness was determined for 11 foods (cream cheese, boiled fish paste, boiled beef, apple, raw carrot, peanut, soft/hard rice cracker, jelly, plain chocolate and chewing gum) and the wax cube. Peak force (N) to compress each item was obtained from force-time curves generated with the Tensipresser. Perceived hardness ratings of each item were made by 30 dentate subjects (mean age 26.9 years) using a visual analogue scale (100 mm). These subjective assessments were given twice with a 1 week interval. High intraclass correlation coefficients (ICCs) for test-retest reliability were seen for all foods (ICC > 0.68; P < 0.001). One-way anova found a significant effect of food type on both the objective hardness score and the subjective hardness rating (P < 0.001). The wax cube showed significant lower objective hardness score (32.6 N) and subjective hardness rating (47.7) than peanut (45.3 N, 63.5) and raw carrot (82.5 N, 78.4) [P < 0.05; Ryan-Einot-Gabriel-Welsch (REGW)-F]. A significant semilogarithmic relationship was found between the logarithm of objective hardness scores and subjective hardness ratings across twelve test items (r = 0.90; P < 0.001). These results suggest the wax cube has a softer texture compared with test foods traditionally used for masticatory performance test, such as peanut and raw carrot. The hardness of the wax cube could be modified to simulate a range of test foods by changing mixture ratio of soft and hard paraffin wax.

Detection system of Cryptosporidium parvum oocysts by brackish water benthic shellfish (Corbicula japonica) as a biological indicator in river water.

The brackish water benthic shellfish, Corbicula japonica, was experimentally exposed to Cryptosporidium parvum oocysts at 1.51x10(4)oocysts/clam/day for 7 or 14 days. Oocysts were predominantly eliminated through the feces of Corbicula japonica in both cases by microscopic and PCR methods. The fecal excretion rates of oocysts within 4 days after the last exposure to Corbicula japonica were 87.6% for the 7-day exposure group and 86.0% for the 14-day exposure group. The tissue residue level of oocysts in the gastrointestinal tract 3 days after the last exposure was 2.7% of total exposed oocysts and that of 7 days was 1.1% for the 7-day exposure case and 1.6 and 0.5% for the 14-day exposure case, respectively, maintaining infectivity to cultured cells (HCT-8) in vitro. At the same time, field tests of Corbicula japonica for collecting oocysts showed that this clam could certainly collect Cryptosporidium parvum oocysts in the natural river and, furthermore, the gene type of C. parvum could be also identified proving its effectiveness as a biological indicator. The present study showed that the brackish water benthic shellfish Corbicula japonica may be capable of gathering and preserving Cryptosporidium parvum oocysts to a considerable extent under the natural ecological conditions, and further suggests the effectiveness of Corbicula japonica as a practical and general bioindicator for estimates of river water contamination by oocysts of Cryptosporidium parvum.

Influence of food platform width of mandibular removable partial denture on food mixing ability.

The aim of this study was to clarify the influence of food platform width on food mixing ability in patients with mandibular removable partial dentures (RPDs). Twelve subjects (six males and six females, mean age 56.8 years) with intact dentition except for unilaterally missing mandibular first and second molars participated in the study. The food platforms of their RPDs were made of light polymerized composite and three platform conditions were evaluated. A food platform (Control condition) had 7 mm width with a central focus on the top of the residual ridge. Narrowed platforms (5 mm) were created by trimming a lingual portion (Buccally oriented occlusion, Buccal condition) or a buccal portion (Lingually oriented occlusion, Lingual condition) from the control. Subjects chewed a standardized wax cube which provided an estimate of food mixing ability [Mixing Ability Index (MAI)] for each of the three platforms. A significant effect (P < 0.001) on the MAI was found for food platform type (repeated measures one-way analysis of variance). Tukey multiple comparisons found significant differences of MAI between Control condition (1.05 +/- 0.26) and Buccal condition (0.86 +/- 0.23) (P = 0.032), and between Control and Lingual condition (0.54 +/- 0.37) (P < 0.001). Furthermore, MAI with Lingual condition was significantly smaller than that with Buccal condition (P < 0.001). These results suggest that reduction in the width of the food platform may impair masticatory function and the buccal portion of mandibular food platform of RPD is more critical for food mixing than the lingual portion of the platform.

The influence of altered occlusal guidance on condylar displacement during submaximal clenching.

As cited in literatures, canine protected occlusion has a potential to reduce clenching induced temporomandibular joint loadings. However, these previous studies did not perform a control of the clenching level which differed with the depending occlusal conditions. This result may be due largely to an associated reduced jaw closing muscle activity. The present study has investigated clenching induced condylar displacements with controlled clenching level. Twenty healthy human subjects (15 males and five females with an average age of 26.5 years) volunteered to participate in this study. Metallic occlusal overlays were fabricated for the lower working side canine and overlaid to the second molar and the non-working side second molar in order to simulate a canine protected occlusion, group function occlusion and bilateral balanced occlusion. Electromyographic (EMG) activity from the bilateral masseter, anterior temporalis, and posterior temporalis was recorded. These signals were rectified, summarized, and presented to each subject using an oscilloscope screen. Using this visual feedback, subjects were asked to perform clenching tasks at a 50% level of maximal voluntary contraction exerted with simulated group function occlusion and three-dimensional condylar displacements were recorded. An experimental occlusal pattern that shows statistically significant affects on condylar displacements (anova: P<0.001) was found. When compared with the simulated canine protected occlusion, the simulated group function occlusion caused smaller working side condylar displacement and the simulated bilateral balanced occlusion caused significantly smaller non-working side and working side condylar displacements. These results suggest that the increased working side tooth contacts have a potential to reduce working side joint loadings, and a balancing side contact has a potential to reduce non-working side joint loadings, under the laboratory condition where the clenching level is controlled.

Detection of improvement in the masticatory function from old to new removable partial dentures using mixing ability test.

The aim of this study was to determine the sensitivity of the Mixing Ability Test to detect improvement of masticatory function in subjects on transition from old to new removable partial dentures. Thirty-two subjects (seven males, 25 females, mean age 65.0 years) with distal extension partially edentulous area in mandible and/or maxilla participated in the study. The following reasons were presented for replacing the old removable partial dentures with new ones: fracture and/or poor fitness of retainers, extraction of abutment teeth, poor fitness of denture base, severe wear of artificial teeth and request for metal base dentures. Masticatory function with old and new removable partial dentures after an adaptation period (mean 27.4 weeks) was evaluated by the Mixing Ability Test. Subjects were asked to masticate five two-coloured wax cubes with each removable partial denture. Mixing Ability Index was obtained from the colour mixture and shape of the masticated cubes. Wilcoxon signed-rank test was used to test the difference of Mixing Ability Indexes between old and new removable partial dentures. The mixing ability indexes with new removable partial dentures (mean+/- s.d.: 0.70+/- 0.68) was significantly higher (P<0.001) than those with old removable partial dentures (-0.11+/-1.13). The results suggest that the Mixing Ability Test was capable of detecting improvement in masticatory function with new removable partial dentures.

Finite element contact stress analysis of the RPD abutment tooth and periodontal ligament.

OBJECTIVES: The purpose of this study was to determine the influence of the occlusal rest position in removable partial dentures on the displacement of the abutment tooth and the stress distribution in the periodontal ligament (PL). METHODS: We constructed three-dimensional finite element models of the mandibular first and second premolars. A layer of the PL and a mesial or distal occlusal rest were produced on the second premolar as an abutment. A zero displacement was prescribed on the outer surface of the PL and the first premolar. In each simulation, the rest was moved 0.05 mm vertically to the apical direction, with or without restriction of horizontal movements. We simulated the contact phenomena on the abutment surfaces, and calculated the movements of the abutment and stress distributions in the PL. RESULTS: We observed a maximum distal displacement of 42 microm at the buccal cusp of the abutment and a principal compressive stress of 0.35 MPa in the PL when the abutment was vertically loaded by a distal rest that was allowed to move horizontally. However, the displacements and stresses were relatively small, and were all within the physiological limitations of the tissues. The restriction of the horizontal movement of the rests was effective in reducing the horizontal displacements of the abutment, regardless of the rest position. CONCLUSIONS: The single vertical load exerted from either the mesial or distal rest on the abutment was unlikely to cause any mechanical damage to its supporting tissues.

Salmonella Enteritidis outbreak associated with a school-lunch dessert: cross-contamination and a long incubation period, Japan, 2001.

A Salmonella Enteritidis (SE) outbreak in Japan was investigated with an observational study, analytical epidemiology and bacteriological examination (including phage typing). The outbreak occurred among 96 schoolchildren, and was caused by SE phage type 1. The outbreak source was dessert buns served at a school lunch (RR 42.55, 95 % CI 5.93-305.11, P < 0.001). The buns were probably cross-contaminated from eggs from a factory with a history of SE-contaminated products. The incubation period was longer than usual (3-16 days, median 8 days). A low contaminating dose may account for the long incubation period and low attack rate. Outbreak detection was hampered by the absence of routine Salmonella surveillance in Japan. The investigation was complicated by concurrent illnesses from other SE phage types. It was successful, in part, because adequate food samples were available for microbiological testing.

Effect of metal strengthener length on stress distribution in acrylic denture bases: a finite element study.

This study investigated the influence of metal strengthener length on stress created in acrylic denture bases in relation to location of the vertical support to the dentures. Finite element analysis was conducted to calculate stress generated in the straps of 2 mm-thickness and 18 mm-width that were reinforced with metal strengtheners of five different lengths. A vertical biting force of 60 N was directed on one end of each strap, while the other end was fixed. Vertical movements were restricted at one of the three support locations between the centre of the strap and the loading site. When the straps were vertically supported near the loading site, greater maximum tensile stresses were seen in the straps with relatively short strengtheners than those shown in the straps with longer strengtheners. The metal strengtheners with sufficient length may provide a preventive denture design against the acrylic fractures.

ProNectin F-grafted-ethylene vinyl alcohol copolymer (EVAL) as a liquid type material for treating cerebral aneurysm--an in vivo and in vitro study.

The authors aimed to develop a liquid material for embolization of aneurysms. In vitro and in vivo performances of the new embolic material were examined by cell culture and using an aneurysm model made in common carotid arteries (CCAs) of adult rats. Engineered protein ProNectin F (PnF), which contains 13 sites of an arginine-glycine-aspartic acid (RGD), was grafted onto ethylene vinyl alcohol copolymer (EVAL-g-PnF). The liquid material, EVAL-g-PnF dissolved in DMSO, was infused into an aneurysm model. The blood segments were harvested 2, 5, and 14 days and examined histologically. A number of bovine coronary artery endothelial cells became able to attach to and form cobblestone-like islands on the EVAL by incorporating PnF. The aneurysm model infused with the EVAL-g-PnF solution revealed that the aneurysm lumen was filled with proliferated fibroblasts and macrophages. On the other hand, the aneurysm model treated with unmodified EVAL showed that the cavity was almost filled with EVAL mass and that fibroblasts and macrophages filled a narrow space between the EVAL mass and the cavity wall. The results indicate that EVAL-g-PnF could be more suitable for reorganizing the cavity of an aneurysm than native EVAL.

3-D Finite element analysis of all-ceramic posterior crowns.

The purpose of this study was to evaluate the stress distribution under various loading conditions within posterior all-ceramic crowns. A three-dimensional finite element model representing a lower first molar was constructed. Variations of the model had two types of single layer all-ceramic crowns (Dicor and Empress) and two types of double layer all-ceramic crowns (In-Ceram and Empress2) cemented. A load of 600 N, simulating the maximum bite force, was applied vertically to the crowns. Loads of 225 N, simulating masticatory force, were applied from three directions (vertically, at a 45 degrees angle, and horizontally). In the test simulating maximum bite force, the maximum tensile stresses on all crowns (17.4-19.4 MPa) concentrated around the loading points. In the masticatory force simulation test, the specimens experienced maximum tensile stresses of 19.7-27.0 MPa under a horizontal load and 10.8-10.9 MPa under a vertical load. When the load was applied horizontally, the maximum tensile stress was observed around the loading points on the surface in the case of the single layer crowns, and of the cervical area of the inner core of the double layer crowns. Within the limitation of this study, it was found that the strength of occlusal contact points is important to the integrity of posterior all-ceramic crowns and that bite forces applied from the horizontal direction are a critical factor.

Bone mineral density of the mandible in ovariectomized rats: analyses using dual energy X-ray absorptiometry and peripheral quantitative computed tomography.

INTRODUCTION: Although previous studies have shown that maxillary molar extraction in ovariectomized (OVX) animals causes mandibular loss of bone, it is still questionable as to whether estrogen deficiency affects mandibles with functional occlusion. MATERIALS AND METHODS: To answer this question, 13-week-old female Sprague-Dawley rats were bilaterally OVX or sham-operated. After 109 days, the bone mineral density (BMD) of the femurs and mandibles was measured using dual-energy X-ray absorptiometry (DEXA) and peripheral quantitative computed tomography (pQCT). RESULTS: In DEXA analysis, although the BMD of the total mandible of the OVX rats was similar to that of the sham-operated rats, the BMD of the condylar region in the OVX rats had decreased by 12.5%. In pQCT analysis, decrease in trabecular BMD of the mandibular bone was detectable but low in the molar region (maximal 13%), whereas no difference was seen in cortical BMD. In the femurs, the trabecular bone prominently decreased in OVX rats (30% decrease in pQCT analysis) as previously reported. CONCLUSION: This study revealed regional differences in the mandibular bone decrease in OVX rats. Although the mechanism of low susceptibility of the mandible to estrogen-deficient conditions remains unknown, it is likely that mechanical stress derived from functional occlusion is preventing bone loss in this pathological condition. Furthermore, this study demonstrated the advantage of pQCT in analyzing rat mandibular bone.

Influence of working side contacts on masticatory function for mandibular distal extension removable partial dentures.

The aim of this study was to clarify the influence of working side contacts for masticatory function for a distal extension removable partial denture. Five subjects who had edentulous arches from second premolar to second molar opposing natural teeth participated. Working side contacts were altered by using three types of artificial teeth attached to the denture base. A-form teeth made contact with opposite teeth while acting as the working side in a lateral excursion. The cusp angles of B- and C-form teeth were decreased by 10 degrees and 20 degrees, respectively compared with A-form teeth. B-and C-form teeth discluded with opposite teeth on the working side. Subjects were asked to perform two kinds of masticatory performance test. Obtained data were evaluated by the repeated-measures anova and the Tukey test for multiple comparisons. Results revealed that there was a significant difference (P=0.001) in the three types of teeth in the mixing ability test and the value of A-form teeth was statistically less value than those of the other teeth. However, there was no significant difference in the comminuting ability test. These results suggested that working side contacts between artificial teeth and opposite natural teeth influenced mixing ability, but not comminuting ability.