Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation.

This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters--co-emulsifier type, aqueous phase type, homogenization temperature--on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution <0.15, zeta potential around -50 mV), containing sodium oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol(®) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting.

2-year observation of attachment loss in a rural Chinese population.

BACKGROUND: Risk indicators for periodontitis seem to vary with study population. The purpose of this study was to determine whether risk indicators of additional attachment loss differ between generations of Chinese villagers in a rural area of China over a 2-year period. METHODS: The study population consisted of 310 subjects aged 15 to 44. In each subject, 2 quadrants from either the upper or lower jaw were randomly selected and 6 sites on each tooth were examined. Clinical parameters included plaque scoring system (PSS), calculus index (CI), probing depth (PD), attachment level (AL), and sulcus bleeding index (SBI). The second examination was done 2 years after the first. RESULTS: In the 15- to 24-year-old age group, mean PSS, CI, and SBI were significantly higher in subjects with additional attachment loss > or =3 mm (AL+) than in those without attachment loss (AL-). In the 25- to 34-year-old age group, mean PD was significantly higher in AL+ than in AL-, and mean PD and AL were significantly higher in AL+ than in AL- in the 35- to 44-year-old age group. Although the number of subjects with AL+ increased with age, the mean number of sites with AL+ per subject did not differ by generation. In addition, smokers tended to exhibit attachment loss more often than non-smokers. CONCLUSIONS: The present results suggest that the clinical parameters associated with attachment loss differ between generations and that gingival inflammation is likely associated with the onset of periodontitis more strongly than progression of periodontitis, whereas PD and/or AL are associated with the progression of periodontitis.

Attachment loss in rural Chinese children over a 3-year period.

OBJECTIVES: The periodontal condition of 84 children (9-14 years old, 38 males and 46 females) in a rural area of China was monitored over a 3-year period in order to determine the clinical parameters that act as risk factors for attachment loss. METHODS: Plaque and calculus accumulation (PSS and CI), modified gingival index (MGI), pocket depth (PD) and attachment level (AL) of two quadrants of each child were examined in 1993 and 1996. Following calculation of the mean of each of these parameters and statistical analysis of the change in each of the clinical parameters over the 3-year period, the relationship between attachment loss and clinical parameters was analyzed using multiple regression analysis. RESULTS: At the beginning of this study, the mean values for males and females were 3.66 and 3.58 for PSS, 1.22 and 1.17 for MGI, 1.07 and 0.90 for CI, 2.21 and 2.22 for PD, and both 0.02 for AL respectively. No significant difference between males and females was observed. After 3 years, all except mean PSS had increased significantly. Multiple regression analysis indicated that AL correlated only to age (P<0.01). In 1993, although the AL was > or =1 mm for at least one site in 21 children, none had an AL> or =3 mm. In 1996, the number of children with an AL> or =1 mm had increased to 63, and nine of these children exhibited 3 mm AL (one to six sites per child). No other significant differences were observed between the clinical data of these nine children and those of the other children. CONCLUSION: Although attachment loss tended to increase with age, no clinical parameters correlated with attachment loss in children.

Detection of bisphenol-A in dental materials by gas chromatography-mass spectrometry.

The xenoestrogenic substance bisphenol-A is widely used as a synthetic precursor of resin monomers, such as bisphenol-A diglycidyl methacrylate. Reports describing the release of bisphenol-A from polymerized resin into saliva have aroused considerable concern regarding exposure to xenoestrogen by dental treatment. The purpose of the present study was to demonstrate a reliable methodology of detecting the trace amounts of bisphenol-A in dental materials. Bisphenol-A was separable from bisphenol-A diglycidyl methacrylate, which is often employed as the principal dimethacrylate monomer, by selective extraction with a Sep-Pak C18 cartridge. Using this extraction method in combination with a gas-chromatography mass-spectrometry, we have obtained evidence that all unpolymerized materials used in this study were contaminated with bisphenol-A. Quantitative analysis using a deuterium-labeled compound as an internal standard revealed bisphenol-A contents in commercial dental materials ranging from < 1 microgram/g material to about 20 micrograms/g material. The polymerized dental materials released up to 91.4 ng bisphenol-A/g material into phosphate buffered saline during 24-h incubation. These results indicate that bisphenol-A can be released from dental materials, however the leachable amount would be less than 1/1000 of the reported dose (2 micrograms/kg body weight/day) required for xenoestrogenisity in vivo.

Resin content in cement liquids of resin-modified glass ionomers.

Qualitative and quantitative analyses were conducted on four kinds of resin-modified glass ionomer (RMGI) cement liquids, LC, LC II, LC III (hereinafter referred to as LCs) and VM, using HPLC and laser Raman spectroscopic methods. HPLC revealed that among the RMGI liquids LCs contain 31-32% HEMA (2-Hydroxyethyl methacrylate), and VM contains 18% of the same. The composition of RMGI cement liquids varied significantly between manufacturers. In Raman spectroscopic analyses, the spectra of liquids of various ratios of polyacrylic acid and HEMA were measured, and calculations were made on the peak intensity ratios of C=C stretch vibration to C=O stretch vibration, common in both HEMA and polyacrylic acid. The composition ratio of polycarboxylic acid to HEMA of commercial glass ionomer cements was assessed by the regression curve generated by a combination of peak intensity ratios and composition ratios. In addition, Raman spectroscopy was able to identity the differences in form of the methacryloyloxy group.

Sexual dimorphism in the tooth crown dimensions of the second deciduous and first permanent molars of Taiwan Chinese.

Sexual dimorphism in the crown components in the second deciduous molar (dm2) and the first permanent molar (M1) of the dental casts taken from Chinese living in Kaohsiung (Taiwan) was investigated. Mesiodistal and buccolingual crown diameters, and 4 main-cusp sizes in the maxillary molars and mesiodistal diameters of the trigonid and talonid in the mandibular molars were measured using a digital caliper (0.01 mm). Percentage sexual differences were calculated. With the exception of trigonid mesiodistal diameters, the mean values of males were larger than females. In both of dm2 and M1 the mean values of the trigonid mesiodistal diameters were slightly larger in females than in males, but the differences were not significant. Percentage sexual dimorphism was smaller in the mesiodistal diameters than in the buccolingual in both dm2 and M1. The crown components showed larger sexual difference in dm2 than in M1, while in the maxilla the external crown size showed larger sexual difference in M1 than in dm2. The buccal cusps showed larger sexual difference than the lingual in the maxillary molars and the talonid showed larger sexual difference than the trigonid in the mandibular. Sexual dimorphism of dm2 and M1 in their crown components displayed similar pattern, although the different degree was noted. This result is thought to relate to the fact these molars belong to the first dentition embryologically.

Efficacy of dentin adhesives in primary and permanent teeth.

The purpose of the present study was to investigate the efficacy of dentin adhesives and to examine acid resistance in primary and permanent teeth. The efficacy of dentin adhesives was evaluated by SEM observation and by measuring the wall-to-wall polymerization contraction gap and dentin hardness before and after conditioning. The detailed mechanism of dentin bonding was the same in both primary and permanent teeth.

Effect of multiple application of dentin bonding agent on marginal integrity of resin composite.

The purpose of the present study was to examine the effect of multiple application of dentin bonding agent to the adhesive surface on the marginal integrity of resin composite. The effect of multiple applications was evaluated by measuring the wall-to-wall polymerization contraction gap and by SEM observation. Multiple application of dentin bonding agent was found to prevent formation of the contraction gap. Although monomer penetration into the enlarged collagen network has been widely discussed as the possible mechanism of the dentin bonding agent and dentin primer, the true detailed mechanism of the dentinal bonding agent and dentin primer should be consistently explained by the prevention of monomer diffusion into the dentin and water contamination of the adhesive interface.

[Studies on the changes of adaptation with children in the dental setting. The relationship between the changes of adaptation and various psychological tests].

The purpose of this study was to discover the changes in the adaptation of children to the Dental setting, and to discover the relationship between the adaptation, and the personality of the child, the personality of the mother, as well as the relationship between the mother and child. The subjects were 60 two to six year old children and their mothers who visited at the Department of Pedodontics, School of Dentistry, Showa University. The results were as follows: 1) The changes of adaptation were classified in groups of four classes. Four groups: Continuous Adaptability (45.0%) Acquired Adaptability (18.3%) Continuous Inadaptability (16.7%) Extreme Inadaptability (20.0%) 2) The inadaptability groups (Continuous Inadaptability and Extreme Inadaptability) of the two to three year old children did not correlate to the change of adaptation and personality of the child, and the relationship between the mother and child. 3) The extreme inadaptability group with the four year old children showed a connection with the change of adaptation and the various Psychological Tests. Concerning personality, the children showed elements of "dependence" "retrogression" and "maladaptation to school (kindergarten)". Concerning the mother child relationship, there were elements of "anxiety" "dotage" "follow blindly" "disagreement". 4) Nobody showed extreme inadaptability in the group of five to six year old children. Continuous Inadaptability group with the five to six year old children showed scarcely any problems. 5) The Personality of mother did not correlate to the change of adaptation of children in the dental setting.

[Dental findings in a case of Chondrodysplasia Punctata].

Chondrodysplasia Punctata is a disease belonging to the metaphysia syndrome. This disease is characterized by endochondral punctata calcification of epiphysis or apophysis, short legs and hands, arthrogryposis, saddle nose, ichthyosis, cataract and mental retardation. This report concerns a case of Chondrodysplasia Punctata (Rhizomeric form) in a 4 year 1 month old girl. Observations were made from the dental point of view, and the findings were as follows: 1) The mesio-distal and bucco-lingual lengths of all primary teeth were smaller than the standard size. 2) Measuring the dental cast, the width of the dental arch was found to be larger, but the length of the arch was found to be smaller than the standard size. 3) The value of the palatal height was slightly smaller, compared with that of the normal children. 4) According to X-ray cephalometric analysis, the growth of the mandible was insufficient. 5) An enlargement of the angles of the teeth axes of the upper and lower central incisors was found. 6) The growth of the basal arches of the maxilla and mandible were shown to be retarded in the anterior portion. 7) Measurement of the area of the tubella sella triangle, revealed the posterior parts to be large and almost standard in the mesofacial part, and small in the mandibulo-facial parts.