bluuebunny/crossref_metadata_2025 huggingface dataset:
Free soluble receptor activator of nuclear factor‐κb ligand in gingival crevicular fluid correlates with distinct pathogens in periodontitis patients
Authors: Sakellari Dimitra , Menti Sofia , Konstantinidis Antonis
Published: October 2008

Aim: The aim of the experiment was to investigate the levels of free soluble receptor activator of nuclear factor‐κb ligand (sRANKL) in periodontal health and disease and their correlations to clinical parameters and important periodontal pathogens.

Material and Methods: Chronic periodontitis (n=35) and periodontally healthy (n=38) subjects participated in the present study. Pocket depth, recession and bleeding index were recorded at a total of 221 sites. Subgingival plaque samples from these sites were analysed for the levels of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola. Gingival crevicular fluid samples were analysed with ELISA for levels of free sRANKL. Comparisons between groups were performed by applying non‐parametric tests (Mann–Whitney) and correlations among parameters were sought for with Spearman's r coefficient.

Results: Mean levels of free sRANKL were higher in periodontitis subjects and correlated significantly with mean counts of T. denticola on the subject level and P. gingivalis, T. denticola on the site level (Spearman's r coefficient, p<0.05), but not with clinical parameters. No correlations were found between the levels of free sRANKL and investigated parameters in periodontally healthy individuals. No effect of smoking was found on investigated parameters and correlations (univariate analysis of variance and pairwise comparisons).

Conclusions: Findings from the present study suggest a correlation of levels of sRANKL with important pathogens in periodontitis patients.
Development of an injectable composite as a carrier for growth factor‐enhanced periodontal regeneration
Authors: Herberg Samuel , Siedler Michael , Pippig Susanne , Schuetz Andreas , Dony Carola , Kim Chong‐Kwan , Wikesjö Ulf M. E.
Published: October 2008

Aim: Biomaterials are often applied in periodontal therapy; however, not always well adapted for tissue regeneration. The objective of this study was to evaluate the physico‐chemical properties and biocompatibility of an injectable, in situ setting composite for growth factor‐enhanced periodontal regeneration.

Material and Methods: The composite constitutes bioresorbable poly(lactic‐co‐glycolic acid) (PLGA) and additives forming in situ a matrix designed as a carrier for recombinant human growth/differentiation factor‐5 (rhGDF‐5). In vitro characterization included the porosity, biointeraction, biodegradation, injectability, and biological activity of released rhGDF‐5. Biocompatibility was compared with granular β‐tricalcium phosphate and an absorbable collagen sponge using a canine periodontal defect model.

Results: The PLGA composite showed a highly porous (500–1000 μm) space‐providing structure. It effectively induced coagulation exhibiting an intimate interaction with the fibrin clot. The biphasic biodegradation was complete within 4 weeks. The composite was conveniently injectable (90.4±3.6 N) for ease of use. It exhibited a sustained rhGDF‐5 release over 4 weeks (40.8%) after initial burst (3.4%) detected by ALP activity. Sites receiving the composite showed limited, if any, residuals and had no appreciable negative effect on periodontal wound healing. There were no noteworthy inflammatory lesions in sites receiving the PLGA composite.

Conclusion: Characteristics of the PLGA composite makes it an attractive matrix to support native wound healing and rhGDF‐5‐enhanced periodontal regeneration.
School‐level contextual factors associated with betel quid chewing among schoolchildren in Taiwan
Authors: Huang Hsiao‐Ling , Lee Chien‐Hung , Yen Yea‐Yin , Chen Ted , Chen Fu‐Li , Ho Pei‐Shan , Lai Tai‐Cheng , Tsai Wen‐Ling , Hsu Chih‐Cheng
Published: October 2008

Abstract –  Objectives:  Previous to this research, no literature had explored the clustering of betel quid chewing at the school‐level and the contextual factors contributing to this behavior among elementary schoolchildren. This study therefore examines this in clusters stratified according to school geography and the rate of aboriginal students in each school. Individual‐level characteristics are controlled in the study.

Methods:  The data used derive from student and parent surveys of the School Smoking Survey Project from a sampling of third and fourth grade children from 13 elementary schools in Tao‐Yuan County, Taiwan (n = 1585). The individual‐ and school‐level characteristics regarding betel quid chewing were estimated using multi‐level logistic regression analysis.

Results:  Compared to their counterparts, students attending schools with higher percentages of aboriginal students (OR = 3.60, 95% CI: 1.31–9.95), or those schools located in a mountainous region (OR = 2.82, 95% CI: 1.19–6.70), were found to have a greater risk of chewing behavior. Other observed characteristics having a significant relationship to student chewing behavior were drinking alcohol and smoking cigarettes.

Conclusions:  The new findings from this study suggest that the specific school attended is an important point of intervention. Therefore, effective policies and preventive programs should be strongly considered for implementation in schools that are putting students at the greatest risk for betel quid chewing behavior. Our study also confirmed the relationship between betel quid chewing, cigarette smoking, and alcohol drinking, suggesting that multifaceted intervention strategies need to be considered in regard to such behaviors among elementary schoolchildren.
Foreign‐body‐associated granulomatous slack skin in folliculotropic mycosis fungoides of childhood
Authors: Tronnier Michael
Published: October 2008

Presented in part at the XXVIII Symposium of the International Society of Dermatopathology, Paris, November 14–17, 2007.

A 13‐year‐old boy developed a bulky mass close to the right axillary region and an infiltrated plaque on the abdominal skin. Two years earlier, the diagnosis of follicular mycosis fungoides has been established. Biopsies of both areas revealed typical features of granulomatous slack skin (GSS). Within some of the giant cells, doubly refractile material of unknown origin was found. It may be speculated that in the reported case of follicular mycosis fungoides in childhood, GSS developed as a specific reaction pattern of the disease because of foreign bodies.
Cdc7 expression in melanomas, Spitz tumors and melanocytic nevi
Authors: Clarke Loren E. , Fountaine Thomas J. , Hennessy Jeannie , Bruggeman Richard D. , Clarke Jennie T. , Mauger David T. , Helm Klaus F.
Published: October 2008

Background:  Cdc7 is a serine‐threonine kinase required for initiation of DNA replication that may play a role in the development and progression of melanoma.

Materials and Methods:  Tissue microarrays containing 40 melanomas, 40 Spitz tumors and 30 nevi were constructed. Staining for Cdc7 was scored semiquantitatively according to intensity and extent, and the values were converted into composite scores.

Results:  Nodular melanomas, atypical Spitz tumors and superficial spreading melanomas had the highest scores (nodular melanomas, 3.67; atypical Spitz tumors, 2.78 and superficial spreading melanomas, 2.44). Typical Spitz nevi, dysplastic nevi and ordinary nevi had the lowest scores. Cdc7 expression in melanomas differed significantly from non‐Spitz nevi (p < 0.001). The difference was also significant when invasive melanomas were compared with dysplastic nevi (p < 0.005) and when invasive melanomas were compared with non‐atypical Spitz nevi (p < 0.001). However, there was no significant difference between invasive melanomas and atypical Spitz tumors (p = 0.69) or between dysplastic nevi and ordinary nevi (p = 0.73).

Conclusion:  Cdc7 expression differs significantly among cutaneous melanocytic neoplasms and can be evaluated by routine immunohistochemical methods. The results suggest that differences in Cdc7 expression may account for some of the differences between malignant melanomas and benign melanocytic nevi.
Predator control and the density and reproductive success of grouse populations in Finland
Authors: Kauhala Kaarina , Helle Pekka , Helle Eero
Published: October 2008

The impact of predator removal or protection on the reproductive success and density of grouse populations was studied experimentally in southern and northern Finland. In predator removal areas small and medium‐sized carnivores wore efficiently hunted, while in predator protection areas hunting was prohibited. Both predator (red fox, raccoon dog, pine marten and stoat) and grouse populations were monitored. The breeding success of grouse, indicated by the young/adults ratio, decreased in the predator protection area in northern Finland during a vole low. Despite a decline in the vole population, the breeding success of grouse did not decline in the predator removal area. The mean brood size during the experiment was significantly higher in the removal areas than in the protection areas both in southern and northern Finland. Predator removal/protection thus affected the reproductive success of grouse, but the impact of control on adult grouse populations was not as evident.
Effect of energy availability, seasonality, and geographic range on brown bear life history
Authors: Ferguson Steven H. , McLoughlin Philip D.
Published: October 2008

Life‐history theory allows predictions of how changes in environmental selection pressures along a species' geographic distribution result in discrete shifts in life‐history traits. We tested for spatial patterns of 24 populations of brown bearsUrsus arctosacross North America that grouped according to the following environmental and population parameters: evapotranspiration as a correlate of primary productivity of vegetation, coefficient of variation of monthly evapotranspiration values as a measure of seasonality. population density, and adult female weight. Cluster analysis grouped brown bear populations into two regions: Pacific‐coastal populations characterized by high population density and large females that lived in areas of high primary productivity and low seasonality. and inland and barren‐ground populations characterized by relatively low density and small bears that lived in areas of low productivity and high seasonality. For each region, we tested whether life‐history traits (age at maturity and interbirth interval) related to primary productivity or seasonality. High altitude (interior: > 1000 m) and high latitude (barren‐ground; >65°N) populations respond to extremes in seasonality with risk‐spreading adaptations. For example, age at maturity and interbirth interval increased with greater seasonality. In contrast, Pacific‐coastal populations living on the western edge of brown bear geographic range respond to intraspecific competition at high densities by maximizing offspring competitive ability. For example, age at maturity increased with greater primary productivity and high population density. In each region, the female parent decided on the life‐history trade‐offs required to reduce the risks of offspring mortality depending on the environmental pattern.
Abundance patterns of European breeding birds
Authors: Gregory Richard D.
Published: October 2008

The frequency distribution of national population sizes of breeding birds was examined for each of 48 European countries, including autonomous regions, using data from the European Bird Database. The frequency distribution of logarithmically transformed abundance was left skewed in 40 countries: there was significant left skew in 10, and positive skew, in 2 countries. The inclusion of data classed as of low quality did not alter the conclusion that abundance patterns were predominantly left skewed. Abundance patterns of resident and migrant breeding birds differed; residents were left skewed, migrants were lognormal. Skewness was correlated negatively the number of species within a country. At low sample size, both left and right skews were evident, but left skews predominated at larger samples sizes. This pattern was driven partly by a difference between breeding populations on islands and on continental countries. Resampling procedures with fixed sample size showed that resident and migrant birds differed consistently in their patterns of skew, independent of sample size. If the birds of Europe were treated as a single assemblage, their abundance pattern was left skewed but this was driven by a very small number of vagrant breeders.
The tempo and mode of gopher mound production in a tallgrass prairie remnant
Authors: Klaas Benjamin A. , Moloney Kirk A. , Danielson Brent J.
Published: October 2008

To gain better insight into how small‐scale disturbances might affect ecological processes, such as the maintenance of plant species diversity, we conducted a two‐year study characterizing spatio‐temporal patterns of gopher mound production on a tallgrass prairie remnant located at Anderson Prairie, Iowa. USA. The locations of all newly produced gopher mounds were mapped on two 80 × 80 m permanent plots. We used these data to characterize spatio‐temporal patterns of mound production across a range of scales. We found that mound production was highly clustered at scales of < 8 m over short periods of time (< 2 weeks), but shifted in location over a 3–4 weeks time period, resulting in a clustered pattern at scales of < 20 m over longer time periods (up to the 2 yr of the study). We also found that patterns of mound production at intermediate spatial scales (> 20 m) remained fairly static over time, although they differed significantly from site to site. The results of this study suggest that small‐scale patterns of variability in mound production may increase habitat variability over very short spatial scales, possibly providing a mechanism that can enhance the development and maintenance of species diversity.
Involvement of laminin and integrins in adhesion and migration of junctional epithelium cells
Authors: Kinumatsu T. , Hashimoto S. , Muramatsu T. , Sasaki H. , Jung H‐S , Yamada S. , Shimono M.
Published: October 2008

Background and Objective:  The junctional epithelium attaches to the enamel surface with hemidesmosomes (of which laminin‐5 and integrin‐α6β4 are the main components) in the internal basal lamina. Laminin‐5 is also involved in cell motility with integrin‐α3β1, although their functions have not yet been clarified. The purpose of this study was to determine the functions of those adhesive components between the tooth and the junctional epithelium during cell migration. Because an idea has been proposed that directly attached to tooth cells (DAT cells) may not contribute to cell migration, 5‐bromo‐2‐deoxyuridine staining was performed to confirm cell migration.

Material and Methods:  We investigated laminin‐γ2 (contained only in laminin‐5), integrin‐β4 (involved in cell–extracellular matrix contact) and integrin‐α3 (inducing cell migration) in the junctional epithelium, oral gingival epithelium and gingival sulcus epithelium of 6‐wk‐old ICR mice using laser microdissection, quantitative real‐time reverse transcription‐polymerase chain reaction, immunofluorescence and 5‐bromo‐2‐deoxyuridine staining.

Results:  Laminin and integrins were clearly immunolocalized in the basal lamina of all epithelium. Quantitative analysis of laminin and integrin mRNAs by laser microdissection showed that they were more highly expressed in DAT cells than in basal cells in the oral gingival epithelium. In particular, a 12‐fold higher expression of laminin‐5 was observed in the junctional epithelium compared with the oral gingival epithelium. 5‐Bromo‐2‐deoxyuridine staining showed rapid coronal migration of DAT cells.

Conclusion:  These results suggest that the abundant expression of laminin‐5 and integrin‐α6β4 is involved in the attachment of DAT cells to teeth by hemidesmosomes. Abundant expression of laminin‐5 and integrin‐α3β1 might assist in DAT cell migration, confirmed by 5‐bromo‐2‐deoxyuridine staining during the turnover of junctional epithelium.
Induction of cementogenesis and periodontal ligament regeneration by recombinant human transforming growth factor‐β3 in Matrigel with rectus abdominis responding cells
Authors: Ripamonti U. , Parak R. , Petit J.‐C.
Published: October 2008

Background and Objective:  In primates and in primates only, the transforming growth factor‐β proteins induce endochondral bone formation. Transforming growth factor‐β3 also induces periodontal tissue regeneration. Two regenerative treatments using human recombinant transforming growth factor‐β3 were examined after implantation in mandibular furcation defects of the nonhuman primate, Papio ursinus.

Material and Methods:  Class III furcation defects were surgically created bilaterally in the mandibular first and second molars of two adult Chacma baboons (P. ursinus). Different doses of recombinant transforming growth factor‐β3 reconstituted with Matrigel® matrix were implanted in the rectus abdominis muscle to induce heterotopic ossicles for subsequent transplantation to selected furcation defects. Twenty days after heterotopic implantation, periodontal defects were re‐exposed, further debrided and implanted with minced fragments of induced heterotopic ossicles. Contralateral class III furcation defects were implanted directly with recombinant transforming growth factor‐β3 in Matrigel® matrix with the addition of minced fragments of autogenous rectus abdominis muscle. Treated quadrants were not subjected to oral hygiene procedures so as to study the effect of the direct application of the recombinant morphogen in Matrigel® on periodontal healing. Histomorphometric analyses on undecalcified sections cut from specimen blocks harvested on day 60 measured the area of newly formed alveolar bone and the coronal extension of the newly formed cementum along the exposed root surfaces.

Results:  Morphometric analyses showed greater alveolar bone regeneration and cementogenesis in furcation defects implanted directly with 75 μg of transforming growth factor‐β3 in Matrigel® matrix with the addition of minced muscle tissue.

Conclusion:  Matrigel® matrix is an optimal delivery system for the osteogenic proteins of the transforming growth factor‐β superfamily, including the mammalian transforming growth factor‐β3 isoform. The addition of minced fragments of rectus abdominis muscle provides responding stem cells for further tissue induction and morphogenesis by the transforming growth factor‐β3 protein.
Areca nut extracts increased expression of inflammatory cytokines, tumor necrosis factor‐α, interleukin‐1β, interleukin‐6 and interleukin‐8, in peripheral blood mononuclear cells
Authors: Chang L‐Y. , Wan H‐C. , Lai Y‐L. , Kuo Y‐F. , Liu T‐Y. , Chen Y‐T. , Hung S‐L.
Published: October 2008

Background and Objective:  Cytokines represent a central role in inflammatory tissue destruction and regulate the immune responses that may govern the progression of periodontal diseases. This study investigated the effects of areca nut extracts on the expression of inflammatory cytokines, tumor necrosis factor‐α, interleukin‐1β, interleukin‐6 and interleukin‐8 in peripheral blood mononuclear cells. The role of oxidative stress of areca nut extracts was also examined using curcumin.

Material and Methods:  The expression of cytokines in peripheral blood mononuclear cells treated with extracts of ripe areca nut or extracts of tender areca nut was analyzed using enzyme‐linked immunosorbent assay and reverse transcription–polymerase chain reaction.

Results:  Both extracts of ripe areca nut (≤ 40 μg/mL) and extracts of tender areca nut significantly enhanced the production of tumor necrosis factor‐α and interleukin‐1β in peripheral blood mononuclear cells in a dose‐dependent and time‐dependent manner. The kinetics of mRNA expression of both cytokines was also enhanced by areca nut extracts. The stimulatory effects of areca nut extracts on the secretion of tumor necrosis factor‐α, interleukin‐1β, interleukin‐6 and interleukin‐8 and on the mRNA expression of tumor necrosis factor‐α, interleukin‐1β and interleukin‐6 at 4 h of incubation were reduced by curcumin (20–50 μm). However, the level of interleukin‐8 transcripts was not affected by curcumin. Moreover, interleukin‐1β induction by extracts of tender areca nut, but not by extracts of ripe areca nut, was weakened by 10 μm curcumin. The inhibitory effects of curcumin may vary with different cytokines and with different areca nut extract treatments.

Conclusion:  The complex cytokine profile induced by areca nut extracts‐treated peripheral blood mononuclear cells implied the possibility of enhanced local inflammation and altered immune functions by the areca chewing habit. The inhibitory effects of curcumin on cytokine expression suggested that oxidative stress might be involved in areca nut extracts‐associated immune alteration.
Mechanical force augments the anti‐osteoclastogenic potential of human gingival fibroblasts in vitro
Authors: Kook S‐H. , Son Y‐O. , Choe Y. , Kim J‐H. , Jeon Y‐M. , Heo J‐S. , Kim J‐G. , Lee J‐C.
Published: October 2008

Background and Objective:  The cellular response of human gingival fibroblasts to a mechanical force is considered to be primarily anti‐osteoclastic because they produce relatively high levels of osteoprotegerin. However, there is little information available on the effects of compression force on the production of osteoprotegerin and osteoclastic differentiation by these cells. In this study, we examined how mechanical force affects the nature of human gingival fibroblasts to produce osteoprotegerin and inhibit osteoclastogenesis.

Material and Methods:  Human gingival fibroblasts were exposed to mechanical force by centrifugation for 90 min at a magnitude of approximately 50 g/cm2. The levels of osteoprotegerin, receptor activator of nuclear factor‐κB ligand (RANKL), interleukin‐1β and tumor necrosis factor‐α were measured at various time‐points after applying the force. The effect of the centrifugal force on the formation of osteoclast‐like cells was also determined using a co‐culture system of human gingival fibroblasts and bone marrow cells.

Results:  Centrifugal force stimulated the expression of osteoprotegerin, RANKL, interleukin‐1β and tumor necrosis factor‐α by the cells, and produced a relatively high osteoprotegerin to RANKL ratio at the protein level. Both interleukin‐1β and tumor necrosis factor‐α accelerated the force‐induced production of osteoprotegerin, which was inhibited significantly by the addition of anti‐(interleukin‐1β) immunoglobulin Ig isotype; IgG (rabbit polyclonal). However, the addition of anti‐(tumor necrosis factor‐α) immunoglobulin Ig isotype; IgG1 (mouse monoclonal) had no effect. Centrifugal force also had an inhibitory effect on osteoclast formation.

Conclusion:  Application of centrifugal force to human gingival fibroblasts accelerates osteoprotegerin production by these cells, which stimulates the potential of human gingival fibroblasts to suppress osteoclastogenesis. Overall, human gingival fibroblasts might have natural defensive mechanisms to inhibit bone resorption induced by a mechanical stress.
Autoantibodies to β1‐adrenoceptors in human chronic periodontitis induce overexpression of fibroblast CD40 and trigger prostaglandin E2 generation
Authors: Sterin‐Borda L. , Furlan C. , Borda E.
Published: October 2008

Background and Objective:  Autoimmune mechanisms may contribute to the pathogenesis of periodontal disease. Autoantibodies with the potential to bind and activate β1‐adrenoceptors (β1‐AR) of human gingival fibroblasts were studied to provide evidence of altered humoral immune response in chronic periodontal disease.

Material and Methods:  Flow cytometry and enzyme‐linked immunosorbent assay using cell culture‐adherent gingival fibroblasts and/or their purified membranes and/or a synthetic peptide corresponding to the second extracellular loop of human β1‐AR were used to detect serum antibodies. The effects of antibodies from chronic periodontal disease patients on PGE2 generation and CD40 expression were also tested.

Results:  Circulating immunoglobulin G (IgG) from chronic periodontal disease patients (but not from normal individuals) interacted with the fibroblast surface, activating β1‐AR. Atenolol or CGP 20712 (beta 1‐AR antagonists) and β1 synthetic peptide inhibited the interaction of IgG with β1‐AR. Immunoglobulin G from chronic periodontal disease patients also displayed agonist‐like activity associated with specific β1‐AR activation, increasing PGE2 generation and CD40 overexpression. The corresponding affinity‐purified anti‐β1‐AR peptide IgG mimicked these effects. Both effects were prevented by inhibition of cyclo‐oxygenase.

Conclusion:  This article supports the participation of humoral immune alterations in chronic periodontal disease resulting in postsynaptic functional deregulation. Overproduction of proinflammatory mediators (PGE2 and CD40 expression) is induced as a consequence of antibody–β1‐AR interaction. The PGE2–CD40–IgG axis may play a part in the pathophysiological mechanisms underlying the inflammatory process in chronic periodontal disease.
Factors affecting human supragingival biofilm composition. II. Tooth position
Authors: Haffajee A. D. , Teles R. P. , Patel M. R. , Song X. , Yaskell T. , Socransky S. S.
Published: October 2008

Background and Objective:  Little is known regarding the factors that affect the microbial composition of supragingival biofilms. This study was designed to test the hypothesis that tooth location affects the microbial composition of supragingival plaque beyond the effect due to plaque mass as reflected by total DNA probe count.

Material and Methods:  Supragingival plaque samples were taken from the mesiobuccal aspect of each tooth in 187 subjects (n = 4745 samples). All samples were individually analyzed for their content of 40 bacterial species using checkerboard DNA–DNA hybridization. Significance of differences in mean species counts and proportions were determined among tooth surfaces and six tooth type categories: molars, bicuspids, incisors/canines in the mandible and maxilla separately using the Kruskal–Wallis test. Stepwise multiple linear regression was employed to examine the relationship between species proportions and total DNA probe count, tooth location, periodontal and smoking status, age and sex.

Results:  All species differed significantly among tooth types and among the six tooth categories. Higher plaque levels were seen on molars and lower incisors. Some differences observed between tooth types could be partly explained by the level of plaque. Teeth with high plaque mass exhibited high levels of Capnocytophaga gingivalis, Actinomyces naeslundii genospecies 2, Campylobacter rectus and Campylobacter showae. However, certain species, such as Veillonella parvula and Streptococcus sanguinis, differed significantly at different tooth locations despite similarities in plaque mass. Twenty of the test species exhibited a significant association with tooth location after adjusting for total DNA probe count and subject level factors.

Conclusion:  While plaque mass was associated with differences in proportions of many species in supragingival biofilms, tooth location also was strongly associated with species proportions in both univariate and multivariate analyses.
Melatonin reduces stress‐activated/mitogen‐activated protein kinases in spinal cord injury
Authors: Esposito Emanuela , Genovese Tiziana , Caminiti Rocco , Bramanti Placido , Meli Rosaria , Cuzzocrea Salvatore
Published: October 2008

Abstract:  Permanent functional deficits following spinal cord injury (SCI) arise from both mechanical injury and from secondary tissue reactions involving inflammation. The mitogen‐activated protein kinases (MAPKs) play a critical role in cell signaling and gene expression. MAPK family includes three major members: extracellular signal regulated kinase (ERK), p38, and c‐Jun N‐terminal kinase (JNK), representing three different signaling cascades. Moreover, various studies have clearly shown that high‐mobility group box 1 (HMGB1) protein is implicated as a putative danger signal involved in the pathogenesis of a variety of inflammatory conditions including autoimmunity, cancer, trauma and hemorrhagic shock, and ischemia‐reperfusion injury. Recently, we have reported that the pineal secretory product melatonin exerts important anti‐inflammatory effects in an experimental model of SCI induced by the application of vascular clips (force of 24 g) to the dura after a four‐level T5–T8 laminectomy. However, no reports are available on the effect of melatonin on MAPK signaling pathways and HMGB1 expression in SCI. The aim of the present study was to evaluate whether the melatonin protective effect observed in SCI is related to the regulation of MAPK signaling pathways and HMGB1 in mice. In this study we demonstrate the efficacy of treatment with the melatonin in SCI in mice in reducing (a) motor recovery, (b) activation of MAPKs p38, JNK and ERK1/2, (c) tumor necrosis factor‐α expression, and (d) expression of HMGB1. We propose that melatonin’s ability to reduce SCI in mice is also related to a reduction in MAPK signaling pathways and HMGB1 expression.
Modulation of the cGMP signaling pathway by melatonin in pancreatic β‐cells
Authors: Stumpf Ina , Bazwinsky Ivonne , Peschke Elmar
Published: October 2008

Abstract:  Melatonin influences the second messenger cyclic guanosine 3′,5′‐monophosphate (cGMP) signaling pathway in pancreatic β‐cells via a receptor‐mediated mechanism. In the present study, it was determined how the regulation of cGMP concentrations by melatonin proceeds. The results provide evidence that melatonin acts via the soluble guanylate cyclase (sGC), as molecular investigations demonstrated that long‐term incubation with melatonin significantly reduced the expression levels of the sGC mRNA in rat insulinoma β‐cells (INS1) cells, whereas mRNA expression of membrane guanylate cyclases was unaffected. Incubation with melatonin abolished the S‐nitrosoacetyl penicillamine‐induced increase of cGMP concentrations in INS1 cells. In addition, the cGMP‐inhibitory effect of melatonin was reversed by preincubation with the sGC inhibitors 1H‐(1,2,4)oxadiazolo(4,3‐α)quinoxalin‐1‐one and 4H‐8‐bromo‐1,2,4‐oxadiazolo(3,4‐d)benz(b)(1,4)oxazin‐1‐one. Nitric oxide (NO) production was not influenced after 1 hr of melatonin application, but was influenced after a 4 hr incubation period. Preincubation of INS1 cells with the NO synthase inhibitor NG‐monomethyl‐l‐arginine did not abolish the cGMP‐inhibitory effect of melatonin. Transcripts of cyclic nucleotide‐gated (CNG) channels were significantly reduced after melatonin treatment in a dose‐dependent manner, indicating the involvement of these channels in mediating the melatonin effect in INS1 cells. The results of this study demonstrate that melatonin mediates its inhibitory effect on cGMP concentrations in pancreatic β‐cells by inhibiting the sGC, but does not influence NO concentration or NO synthase activity in short‐term incubation experiments. In addition, it was demonstrated that melatonin is involved in modulation of CNG channel mRNA.
Comparison of closed chamber and open chamber evaporimetry
Authors: Cohen J. C. , Hartman D. G. , Garofalo M. J. , Basehoar A. , Raynor B. , Ashbrenner E. , Akin F. J.
Published: October 2008

Background: Recently it has been asserted that a closed chamber evaporimeter, the VapoMeter, offers advantages over standard open chamber devices in measuring transepidermal water loss (TEWL). Purported improvements include the ability to take measurements at any angle, short reading times and insensitivity to external air currents. These claims are compelling, considering that measuring TEWL at diverse skin sites can be tedious, especially with children. The primary aim of this study was to compare the performance of closed and open chamber instruments when they were held at various angles and, secondly to evaluate the ability of the devices to discriminate between test conditions.

Methods: The performance of closed chamber (VapoMeter) and open chamber (DermaLab®) evaporimeters were compared by measuring water vapor emitted from IMS Vitro‐skin® that had been hydrated to a predetermined level. Measurements were taken at three angles from vertical – 0°, 45°, and 90°. Vitro‐skin® samples were weighed periodically throughout the experimental phase to verify water loss rates.

Results: Both the VapoMeter and the DermaLab® yielded significantly lower water loss values when held at angles that varied from the vertical (0°) position, indicating that the closed chamber device is no more capable of accurately measuring TEWL at any angle than an open chamber instrument. The DermaLab® provided better discrimination than the VapoMeter when the instruments were held vertically, as is the only prescribed testing position for open‐chamber instruments. The VapoMeter was easier to use than the DermaLab®; however, there was evidence that the sealed chamber could become saturated under high water loss conditions.

Conclusions: Previous assertions that the VapoMeter closed chamber evaporimeter is capable of measuring TEWL regardless of angle were not validated. Each device appeared capable of accurately estimating water loss rates only in the vertical position. Although the VapoMeter was easier to use than the open chamber device, its tendency to become saturated under high water loss conditions could be a disadvantage when assessing dynamic TEWL.
Transient TWEAK overexpression leads to a general salivary epithelial cell proliferation
Authors: Sugito T , Mineshiba F , Zheng C , Cotrim AP , Goldsmith CM , Baum BJ
Published: October 2008

Objectives:  Tumor necrosis factor‐like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that has pro‐apoptotic, pro‐angiogenic and pro‐inflammatory effects. In liver, TWEAK leads to proliferation of progenitor oval cells, but not of mature hepatocytes. This study evaluated the hypothesis that TWEAK overexpression in salivary glands would lead to the proliferation of a salivary progenitor cell.

Methods:  A recombinant, serotype 5 adenoviral vector encoding human TWEAK, AdhTWEAK, was constructed, initially tested in vitro, and then administered to male Balb/c mice via cannulation of Wharton’s duct. TWEAK expression in vivo was monitored as protein secreted into saliva and serum by enzyme‐linked immunosorbent assays. Salivary cell proliferation was monitored by proliferating cell nuclear antigen staining and apoptosis was monitored using TUNEL staining.

Results:  AdhTWEAK administration led to a dose‐dependent, transient TWEAK protein expression, detected primarily in saliva. Salivary epithelial cell proliferation was generalized, peaking on ∼days 2 and 3. TWEAK expression had no detectable effect on apoptosis of salivary epithelial cells.

Conclusion:  Transient overexpression of TWEAK in murine salivary glands leads to a general proliferation of epithelial cells vs a selective stimulation of a salivary progenitor cell.
JunB as a potential mediator of PTHrP actions: new gene targets Ephrin B1 and VCAM‐1
Authors: Berry JE , Pettway GJ , Cordell KG , Jin T , Datta NS , McCauley LK
Published: October 2008

Parathyroid hormone‐related protein (PTHrP) is an integral mediator of physiologic and pathologic processes and has demonstrated actions in the periodontium. PTHrP functions via AP‐1, and specifically through JunB. This study identified JunB‐dependent downstream mediators of PTHrP using OCCM cementoblastic transfectants with JunB over‐ or reduced expression. Over‐expressing cells showed an increase in proliferation, while the opposite was seen in siRNA transfected cells. Microarray analysis of over‐expressing cells revealed more than 1000 regulated genes. Three genes were investigated in more detail. The PTH/PTHrP receptor (PTHR1) and ephrin B1 (EfnB1) were down‐regulated, and vascular cell adhesion molecule‐1 (VCAM‐1) was up‐regulated with JunB over‐expression. JunB siRNA transfectants had increased PTHR1, but reduced ephrin B1 and unaltered VCAM‐1 in vitro. To validate these targets, parental OCCM cells and primary osteoblasts were treated with PTHrP, resulting in reduced PTHR1 and ephrin B1, and increased VCAM‐1. Cell transfectants were implanted subcutaneously in vivo, and microarray analysis and RT‐PCR performed. Over‐expression of JunB down‐regulated PTHR1 and ephrin B1, and increased VCAM‐1. JunB siRNA transfectant implants had increased PTHR1 and ephrin B1, but no altered VCAM‐1. These data highlight new gene targets for PTHrP and indicate JunB is a critical mediator of PTHrP actions.
PI3K/Akt mediates expression of TNF‐α mRNA and activation of NF‐κB in calyculin A‐treated primary osteoblasts
Authors: Qiu L , Zhang L , Zhu L , Yang D , Li Z , Qin K , Mi X
Published: October 2008

Objective:  The effect of calyculin A (CA), a serine/threonine protein phosphatase inhibitor, on tumor necrosis factor‐α (TNF‐α) in primary osteoblasts was investigated to determine whether protein phosphatases could affect primary osteoblasts and if so which signaling pathways would be involved.

Materials and methods:  Primary osteoblasts were prepared from newborn rat calvaria. Cells were treated with 1 nM CA for different time periods. The expressions of TNF‐α and GAPDH mRNA were determined by RT‐PCR. Cell extracts were subjected to SDS‐PAGE and the activation of Akt and NF‐κB were analyzed by western blotting.

Results:  Calyculin A‐treatment markedly increased the expression of TNF‐α mRNA and enhanced the phosphorylation level of Akt (Ser473) in these cells. Pretreatment with the PI3K inhibitor LY294002 suppressed the increase in TNF‐α mRNA expression and the phosphorylation of Akt in response to CA. Western blot analysis showed that CA stimulated the phosphorylation and nuclear translocation of NF‐κB in primary osteoblasts, and these responses were blocked by pretreatment with LY294002.

Conclusion:  Calyculin A elicits activation of PI3K/Akt pathway which leads to expression of TNF‐α mRNA and activation of NF‐κB. This NF‐κB activation involves both phosphorylation and nuclear translocation of NF‐κB.
Process of developing people‐centered care
Authors: KOMATSU Hiroko
Published: October 2008

Aim:  This study, conducted in the last year of the 5 year Center of Excellence Program, aimed to identify the core elements of the developmental process of implementing people‐centered care.

Method:  The members of the team that conceptualized people‐centered care interviewed 25 participants of each research project, including community members. The interview audiotapes were transcribed verbatim and the transcriptions were analyzed using interpretive data.

Results:  The developmental process identified the core elements of people‐centered care: (i) a partnership approach based on equal footing; (ii) capacity‐building by partnership; (iii) mutually generating and utilizing organizational care; and (iv) the expansion and development of organizational care. St Luke's College of Nursing, Tokyo, Japan, is using people‐centered care to send visionary and philosophical messages to society and to demonstrate the specific approaches and techniques to implement such care.

Conclusions:  People‐centered care is implemented in the community as an organizational model using the core elements of the developmental process. The concept of people‐centered care and its realization via a practical approach will be widely applied in future health‐care practise, education, and research.
Dietary guidance for older patients with diabetes mellitus and their primary caregivers using a Model Nutritional Balance Chart
Authors: SATOH Atsuko , SAKURADA Toshiko , HATAKEYAMA Aiko , FUKUOKA Yumiko , HATAKEYAMA Reiko , SASAKI Hidetada
Published: October 2008

Aim:  Dietary control of diabetes mellitus becomes hard in care‐dependent older patients staying at home due to the difficulty of understanding nutritional balance by their primary caregivers. In the present study, an easily handled Model Nutritional Balance Chart (MNBC) for care‐dependent older patients with diabetes mellitus and their primary caregivers was investigated.

Methods:  Nine care‐dependent older patients with diabetes mellitus and their primary caregivers received dietary guidance using the MNBC once per month for 6 months. Nine control care‐dependent older patients with diabetes mellitus and their primary caregivers did not receive dietary guidance but cooperated in providing data once per month. The medicines for the patients were kept the same during the entire length of the study. The effectiveness of the program was judged by changes in nutritional balance and hemoglobin A1c (HbA1c) values.

Results:  Improvements in nutritional balance were observed in relation to fish, fruit, oil, and sugar. The HbA1c values significantly decreased after 6 months in the intervention group, while the HbA1c values in the control group did not change.

Conclusion:  Our guidance method seems to be useful for care‐dependent older patients with diabetes mellitus who are staying at home with their primary caregivers.
Predictors of pressure ulcer and physical restraint prevalence in Japanese acute care units
Authors: IBE Toshiko , ISHIZAKI Tamiko , OKU Hiromi , OTA Kayo , TAKABATAKE Yuriko , ISEDA Akiko , ISHIKAWA Yoko , UEDA Aya
Published: October 2008

Aim:  To investigate the predictors of pressure ulcer and physical restraint prevalence in Japanese acute care units and their relationship to the nursing hours, skill mix, and Nursing Need Scores (NNS).

Methods:  In this descriptive study, quantitative methods were employed to determine if pressure ulcers and physical restraint prevalence, as outcomes of nursing care, were related to the nursing hours, skill mix, and intensity of nursing‐care needs. The sample included 87 acute care units in 42 hospitals in Tokyo and its surrounding prefectures in Japan. The NNS was used as the instrument to measure the intensity of nursing‐care needs. The data were analyzed with descriptive statistics, correlations, and multiple regression analyses.

Results:  Pressure ulcer prevalence was positively correlated with the NNS‐A and NNS‐B. Physical restraint use was positively correlated with the NNS‐B and negatively correlated with the NNS‐A. However, the total nursing hours per patient day was positively related with both pressure ulcer and physical restraint prevalence.

Conclusions:  The nursing hours and NNS are predictors of pressure ulcer development and physical restraint use. The results also suggest that we should revise our process of nursing care. Many functions that might be shared with other personnel are performed by nurses, which results in longer total nursing hours but shorter direct nursing hours, used in order to observe and care for patients. Japan's aging population will result in higher NNS, requiring more direct nursing hours and other personnel to participate in our process of nursing care.
Combination of KIR 2DL2 and HLA‐C1 (Asn80) confers susceptibility to type 1 diabetes in Latvians
Authors: Shastry A. , Sedimbi S. K. , Rajalingam R. , Nikitina‐Zake L. , Rumba I. , Wigzell H. , Sanjeevi C. B.
Published: October 2008

Killer immunoglobulin‐like receptors (KIRs) are known to modulate natural killer (NK) and NK T‐cell function by interacting with human leucocyte antigen (HLA) class I ligands on target cells. The aim of our study was to investigate the influence of KIR2D genes with their HLA‐C ligands in susceptibility to type 1 diabetes. A total of 98 type 1 diabetes patients and 70 healthy subjects from Latvia were typed for KIR genes and HLA‐C ligands using polymerase chain reaction‐based genotyping. The HLA C1+/C2+ combination was positively, and C1–/C2+ combination was negatively, associated with type 1 diabetes. Stratification analysis of KIR/HLA‐C ligand combinations showed 2DL2+/C1+, 2DL3+/C1+, and 2DS2+ /C1+ to be positively, and 2DL2–/C1– and 2DS2–/ C1– to be negatively, associated. The presence of 2DL2‐HLA‐C1 in the absence of 2DS1, 2DS2 confers maximum susceptibility. Absence of 2DL2 and HLA‐C1 along with absence of 2DS1 and 2DS2 confer maximum protection. A hypothetical model of KIR/ligand combinations on immune responses and type 1 diabetes susceptibility is proposed. Our results suggest that a combination KIR2DL2‐ HLA‐C1 plays a critical role in susceptibility or protection in Latvians against type 1 diabetes.
[Ne ii] emission-line profiles from photoevaporative disc winds
Authors: Alexander R. D.
Published: October 2008

I model profiles of the [Ne ii] forbidden emission line at 12.81 μm, emitted by photoevaporative winds from discs around young, solar mass stars. The predicted line luminosities (∼10−6 L⊙) are consistent with recent data, and the line profiles vary significantly with the disc inclination. Edge-on discs show broad (30–40 km s−1) double-peaked profiles, due to the rotation of the disc, while in face-on discs the structure of the wind results in a narrower line (≃10 km s−1) and a significant blueshift (5–10 km s−1). These results suggest that the observations of [Ne ii] line profiles can provide a direct test of models of protoplanetary disc photoevaporation.
Detection of the 2175 Å extinction feature and 21-cm absorption in two Mg ii systems at z ∼ 1.3
Authors: Srianand R. , Gupta N. , Petitjean P. , Noterdaeme P. , Saikia D. J.
Published: October 2008

We have discovered two dusty intervening Mg ii absorption systems at z∼ 1.3 in the Sloan Digital Sky Survey (SDSS) data base. The overall spectra of both quasi-stellar objects (QSOs) are red (u−K > 4.5 mag) and are well modelled by the composite QSO spectrum reddened by the extinction curve from the Large Magellanic Cloud (LMC2) Supershell redshifted to the rest frame of the Mg ii systems. In particular, we detect clearly the presence of the ultraviolet (UV) extinction bump at λrest∼ 2175Å. Absorption lines of weak transitions like Si iiλ1808, Cr iiλ2056, Cr ii+ Zn iiλ2062, Mn iiλ2594, Ca iiλ3934 and Ti iiλ1910 from these systems are detected even in the low signal-to-noise ratio and low-esolution SDSS spectra, suggesting high column densities of these species. The depletion pattern inferred from these absorption lines is consistent with that seen in the cold neutral medium of the LMC. Using the LMC AV versus N(H i) relationship, we derive N(H i) ∼ 6 × 1021 cm−2 in both systems. Metallicities are close to solar. Giant Metrewave Radio Telescope (GMRT) observations of these two relatively weak radio QSOs (fν∼ 50 mJy) resulted in the detection of 21-cm absorption in both the cases. We show that the spin temperature of the gas is of the order of or smaller than 500 K. These systems provide a unique opportunity to search for molecules and diffuse interstellar bands at z > 1.
Rationality Disputes – Psychology and Epistemology
Authors: Rysiew Patrick
Published: October 2008

This paper reviews the largely psychological literature surrounding apparent failures of human rationality (sometimes referred to as ‘the Rationality Wars’) and locates it with respect to concepts and issues within more traditional epistemological inquiry. The goal is to bridge the gap between these two large and typically disconnected literatures – concerning rationality and the psychology of human reasoning, on the one hand, and epistemological theories of justified or rational belief, on the other – and to do so in such as way as to expose interesting points of contact and convergence between them.
A survey of bone fractures in the cat
Authors: Hill F. W. G.
Published: October 2008

A survey of 108 bone fractures in the cat was made over a 1 year period in a city practice in south west England. Seventy‐three per cent involved the pelvic limb. The three bones most commonly affected were femur (38%), pelvis/sacrum (22%) and mandible (16%). Forty‐five cases were the result of road accidents and 75% of cats were 2 years old or less.

Treatment of femoral shaft fractures by intramedullary pinning gave good results. The majority of proximal epiphyseal separations and femoral neck fractures responded well to conservative treatment. ‘Cage rest’ was used successfully to treat severely comminuted femoral shaft fractures. All cases of pelvic fracture were treated conservatively (up to 3 weeks ‘cage rest’). Separation of the mandibular symphysis and fracture of the horizontal ramus healed readily. Repair of tibial (10%) and humeral (5%) fractures was without complications.