bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in the incidence, mortality, and survival rates of oral and pharyngeal cancer in a high‐risk area in Michigan, USA
Authors: Kolker Justine L. , Ismail Amid I. , Sohn Woosung , Ramaswami Neerrajah
Published: July 2007

Objective:  The aim of this analysis was to analyze the incidence, mortality and survival rates for the city of Detroit and Wayne County, Michigan. In Detroit, about four out of the five residents are African‐Americans.

Methods:  Rates and standard errors on oral cancer incidence, survival, and mortality by county of residence, race, gender, stage of diagnosis were provided by the Michigan Cancer Surveillance Program, which is maintained by the Michigan Department of Community Health. Rates were expressed per 100 000 individuals and age adjusted to reflect the distribution of the USA population in 2000. Analysis for trends was conducted by the authors using the National Cancer Institutes’ joinpoint regression program (version 3.0).

Results:  In 1993–2002, the incidence rate of oral cancer in Michigan (one of the 50 states in the USA) was 11.3 per 100 000, and in the city of Detroit, it was 16.6. In African‐American males in Michigan the incidence rate was 24.3 per 100 000, one of the highest among all American males. The city of Detroit, with 9% of the total state population, had 13.1% of all new cases. Between 1993 and 2002, there was a drop in incidence rates in Michigan and Detroit. However, there was an increase in mortality rates in Michigan and Detroit between 2000 and 2002. In Detroit, the incidence and mortality rates of ‘white’ and African‐American males were not different and the highest incidence rates were found in adults between the ages of 50 and 74 years. In the state, the peak incidence rates were found in adults 75 years or older. In 2000–2002, residents of Detroit had the lowest percentage (28.3%) of cases detected at early cancerous stage (in situ or localized) compared with rates in Michigan. African‐Americans in Michigan had a 5‐year survival rate of 34.9% compared with the state average of 54.6%.

Conclusions:  African‐American males in Detroit accounted for a larger proportion of the oral cancer cases relative to their population size. There was surprising similarity between the incidence and mortality rates of African and ‘white’ Americans in Detroit. While the incidence rates have declined in Michigan and Detroit, mortality rates have increased between 2000 and 2002. This finding is contrary to national trends. In order to target programs to prevent oral cancer, oral cancer statistics for in small areas or high‐risk populations should be evaluated separately.
A preliminary investigation of the relationship of dental fear to other specific fears, general fearfulness, disgust sensitivity and harm sensitivity
Authors: Armfield Jason M.
Published: July 2007

Abstract –  Objectives:  People with dental fear often suffer from other psychological disorders, as well as from a number of other specific fears. Fear of going to the dentist may be associated not only with general fearfulness, but also with underlying personality dispositions. This exploratory study, therefore, investigated the associations between dental fear and 67 other specific fears, general fearfulness, disgust sensitivity and harm sensitivity.

Methods:  Participants were 88 Australian adults who were administered the Fear Survey Schedule III (FSS‐III), the Harm Sensitivity Index and the Disgust Sensitivity Index. Principle axis factor analysis with Promax rotation was used to examine how dental fear related to other specific fears as measured with the FSS‐III.

Results:  Dental fear was significantly correlated with most of the other specific fears, with factor analysis indicating that it tended to load more with fears related to lack of control rather than with what have often been classed as ‘medical’ fears. Significant associations were found between dental fear and the personality dispositions of general fearfulness, harm sensitivity and disgust sensitivity, although these associations were not linear.

Conclusions:  Findings reveal extensive co‐occurrence of other specific fears with dental fear, while the associations of dental fear with personality traits suggest enduring aspects to dental fear which may translate into difficulties in fear alleviation. Dental fear was more related to a diverse range of fears relating to a loss of control than to medical‐specific fears.
Water fluoridation as a marker for sociodental inequalities
Authors: Gabardo Marilisa Carneiro Leão , Da Silva Wander José , Moysés Simone Tetu , Moysés Samuel Jorge
Published: July 2007

Abstract –  Objectives:  The aim of this study was to investigate the associations between the Human Development Index at city level (HDI‐M) in the state of Paraná, Brazil, and the length of time of population exposure to water fluoridation (time span) with the respective mean decayed, missing and filled teeth (DMF‐T) of schoolchildren in the state, looking at possible inequalities in these associations.

Methods:  The HDI–M of 323 cities in the state of Paraná, Brazil, was correlated to the duration of exposure to water fluoridation, calculated in number of days. Correlation between the HDI‐M and the DMF‐T indexes for 12‐year‐old children was also performed.

Results:  Correlations were statistically significant, showing that in the cities with a better HDI‐M, water fluoridation had been implemented earlier (squared coefficient correlation of 22%). The fluoridation time span accounted for around 11% of the variance in the DMF‐T indexes of the cities. The correlation indicated that locations with a better HDI‐M had a better DMF‐T, owing to the probable mediating effect of receiving fluoridation earlier. Furthermore, the cost of water fluoridation to benefit the population that has access to this public health measure has been estimated at USD 0.15 per capita/year.

Conclusions:  It is possible to conclude that this low‐cost measure is able to improve oral health status in general. Nevertheless, in the Brazilian areas studied, fluoridation seems to reflect existing social development inequalities, as it was first made available in more socially developed areas, thus bearing an influence on their higher DMF‐T performance to date.
Does malocclusion influence the adolescent's satisfaction with appearance? A cross‐sectional study nested in a Brazilian birth cohort
Authors: Peres Karen Glazer , Barros Aluísio J. D. , Anselmi Luciana , Peres Marco Aurélio , Barros Fernando C.
Published: July 2007

Abstract – Objectives: To test whether malocclusion had an impact on adolescents’ appearance satisfaction regardless of other physical aspects.

Methods: A cross‐sectional study nested in a birth cohort study was carried out in Pelotas, Brazil. A random sample of 900 15‐year‐old adolescents was selected. WHO criteria were used to define malocclusion and a questionnaire was administered including self‐reported skin colour and appearance satisfaction. Dental caries were assessed. Height and weight were measured and body mass index calculated. Data concerning gender and socioeconomic characteristics were obtained from the cohort's perinatal study. Adjusted analyses including all confounding variables investigated were performed using Poisson regression with robust variance in order to identify the potential risk factors for appearance dissatisfaction. All analyses were carried out separately by gender.

Results: The sample included 867 individuals, 54.1% men. The prevalence of moderate or severe malocclusion was 30.6% (95% CI: 26.5–34.7) among boys, and 32.8% (95% CI: 28.2–37.4) among girls (P = 0.524). Dissatisfaction with appearance was reported by 29.8% of the boys and by 46.5% of the girls (P < 0.001). A positive association between malocclusion and appearance dissatisfaction, controlling for other physical, dental caries and socioeconomic characteristics was observed only in girls [prevalence ratio = 1.4 (1.3–1.7)].

Conclusions: Malocclusion is a common condition and is positively associated with appearance dissatisfaction in adolescent girls. The effect of different types of malocclusion on appearance dissatisfaction should be the focus of further investigation.
Sodium metabisulfite allergy is common but is it relevant?
Authors: Madan Vishal , Walker Stephen L. , Beck Michael H.
Published: July 2007

Positive patch tests to sodium metabisulfite (SMB) are frequent. Standard series patch testing to SMB in 1751 patients showed 71 reactions interpreted as positive and allergic. 33 (46.5%) reactions were originally reported as relevant and 38 (53.5%) were of unexplained relevance depending on the presence or absence of identifiable sources responsible for the presenting dermatitis. A breakdown of these findings is presented. An additional detailed study of the sources of SMB in the environment and a retrospective analysis of these results have been undertaken to identify further, possibly overlooked sources of SMB exposure based on the occupational and recreational history. Most of the positive reactions in the relevant group were attributed to the use of Trimovate® cream (63%). 5 patients (13%) with positive reactions in the unexplained relevance group were potentially exposed to SMB in local anaesthetic solutions while at work. 3 patients in the unexplained relevance group (7.8%) and 4 (12.1%) in the relevant group had potential for occupational exposure to SMB as bakers or caterers. Overall, occupational exposure was considered as a possible source of sensitization in 10 (26.3%) patients in the unexplained relevance group. We propose that sensitization to SMB from parenteral solutions and occupational exposure from food handling may account for some of the otherwise unexplained positive patch test reactions. A detailed occupational history should be therefore be sought in otherwise unexplained positive reactions to SMB. We also propose that it is worthwhile including SMB in our standard series in the UK.
Chemical changes in rubber allergens during vulcanization
Authors: Bergendorff Ola , Persson Christina , Lüdtke Anna , Hansson Christer
Published: July 2007

Allergic contact dermatitis to rubber is caused by residues of chemicals used in manufacturing a rubber product. Several different additives are used to achieve a final product of the desired characteristics. Accelerators such as thiurams, dithiocarbamates, and mercaptobenzothiazoles are often among the additives responsible for allergic reactions recognized by dermatologists. The chemistry of the vulcanization process is complicated; as it occurs at an elevated temperature with a mixture of reactive chemicals, the compositions of the initial and final products differ. This paper investigates the changes in composition of common allergens during vulcanization, doing so by chemically analysing various rubber formulations at different stages of the process. Major changes were found in which added chemicals were consumed and new ones produced. An important observation is that thiuram disulfides rarely appear in the final rubber although they may have been used as additives. Instead, thiurams are often converted to dithiocarbamates or to products formed by addition to mercaptobenzothiazole structures, if these have been used together with thiurams as accelerators.
Benzoyl peroxide: is it a relevant bone cement allergen in patients with orthopaedic implants?
Authors: Treudler Regina , Simon Jan C.
Published: July 2007

Contact allergies to orthopaedic implant material are discussed to be relevant for postoperative complaints. We aimed at determining the prevalence of sensitizations to implant metals and to bone cements in patients with implants. We investigated 13 consecutive patients with suspicion of contact allergy to implant material. Epicutaneous patch testing was performed with metals and bone cement components including benzoyl peroxide (BPO). The chief complaints were skin disorders (n = 3), loosening of implant (n = 2), swelling (n = 6), and pain (n = 2). 6 patients had a sensitization to at least 1 allergen. 3 patients reacted to BPO, being of possible relevance in 1 of these patients suffering from dermatitis. Other sensitizations, such as those to nickel, fragrance, and balsam of Peru, were observed, with no clinical relevance (n = 1, respectively). BPO in bone cements may lead to type 4 sensitizations of which the relevance, however, remains questionable. Nevertheless we recommend this allergen to be tested in patients with complicated cemented orthopaedic implants.
The influence of type I diabetes mellitus on the expression and activity of gelatinases (matrix metalloproteinases‐2 and ‐9) in induced periodontal disease
Authors: Silva J. A. F. , Lorencini M. , Peroni L. A. , De La Hoz C. L. R. , Carvalho H. F. , Stach‐Machado D. R.
Published: July 2007

Background and Objective:  Periodontal disease corresponds to a group of lesions that affect the tooth‐supporting tissues present in the dental follicle. Although bacterial plaque is important, the immune response also contributes to the destruction of periodontal tissues. Diabetes mellitus is closely associated with the development, progression and severity of periodontal disease because it not only affects extracellular matrix organization but also the tissue response to inflammation. The objective of the present investigation was to study the influence of diabetes on experimental periodontal disease by evaluating the degradation of extracellular matrix through the analysis of matrix metalloproteinase (MMP)‐2 and MMP‐9 expression and activity, using immunofluorescence, zymography and real‐time reverse transcription‐polymerase chain reaction.

Material and Methods:  Wistar rats were divided into normal and diabetic groups and evaluated 0, 15 and 30 d after the induction of periodontal disease by ligature.

Results:  MMP‐2 and ‐9 were detected in epithelial cells, in the blood vessel endothelium and in connective tissue cells. The same profile of enzymatic expression of MMP‐2 and ‐9 was observed in normal and diabetic animals, with a peak in activity at day 15 of inflammation. However, in diabetic animals, MMP‐2 gelatinolytic activity was reduced after the inflammatory stimulus, whereas that of MMP‐9 was increased. MMP‐2 gene expression decreased with inflammation in both normal groups and groups with diabetes. In contrast, MMP‐9 expression increased in normal animals and decreased in diabetic animals after inflammation.

Conclusion:  The results suggest the involvement of MMP‐2 and ‐9 in the dynamics of periodontal disease and that variation in their expression levels results in differences in tissue organization and wound healing in normal and diabetic animals.
Imaging of intradermal tattoos by optical coherence tomography
Authors: Morsy Hanan , Mogensen Mette , Thrane Lars , Jemec Gregor B. E.
Published: July 2007

Background/purpose: Tattoos have become increasingly popular followed by a growing demand for tattoo removal, and yet there is little knowledge and monitoring of tattoo pigment deposition in skin layers. The purpose of this pilot study is to describe optical coherence tomography image characteristics of intradermal tattoos.

Methods: We included five black tattoos in 3 female volunteers, 39, 35 and 30 years old. In vivo imaging of tattoo pigments in the skin is possible with optical coherence tomography (OCT), a novel non‐invasive, in vivo optical imaging technology with a resolution and a penetration in skin high enough for visualization of tattoo pigment in the dermis.

Results: In optical coherence tomography images tattoo pigments clusters appear as dark, homogenous vertical columns and structures in the papillary dermis. OCT‐scanned normal skin (without tattoos) appeared to be free of this dark structure.

Conclusion: We have demonstrated that OCT can be used to visualize clusters of light absorbing pigments in a predictable manner.
Snc1p v‐SNARE Transport to the Prospore Membrane During Yeast Sporulation is Dependent on Endosomal Retrieval Pathways
Authors: Morishita Masayo , Mendonsa Rima , Wright Jennifer , Engebrecht JoAnne
Published: July 2007

Vesicular traffic is essential for sporulation in Saccharomyces cerevisiae. The Golgi‐associated retrograde protein (GARP) tethering complex is required for retrograde traffic from both the early and late endosomes to the Golgi. Analyses of GARP complex mutants in sporulation reveal defects in meiotic progression and spore formation. In contrast, inactivation of the retromer complex, which mediates vesicle budding and cargo selection from the late endosome, or Snx4p, which is involved in retrieval of proteins from the early endosome, has little effect on sporulation. A retromer GARP double mutant is defective in the formation of the prospore membrane (PSM) that surrounds the haploid nuclei. In the retromer GARP double mutant, PSM precursor vesicles carrying the cargo, Dtr1p, are transported to the spindle pole body (SPB), where PSM formation is initiated. However, the v‐SNARE Snc1p is not transported to the SPB in the double mutant, suggesting that the defect in PSM formation is because of the failure to retrieve Snc1p, and perhaps other proteins, from the endosomal pathway. Taken together, these results indicate that retrograde trafficking from the endosome is essential for sporulation by retrieving molecules important for PSM and spore wall formation.
Regulation of Copper‐Dependent Endocytosis and Vacuolar Degradation of the Yeast Copper Transporter, Ctr1p, by the Rsp5 Ubiquitin Ligase
Authors: Liu Jingxuan , Sitaram Anand , Burd Christopher G.
Published: July 2007

The Saccharomyces cerevisiae high‐affinity copper transporter, Ctr1p, mediates cellular uptake of Cu(I). We report that when copper (50 μm CuSO4) is added to the growth medium of copper‐starved cells, Ctr1p is rapidly internalized by endocytosis, delivered to the lumen of the lysosome‐like vacuole and slowly degraded by vacuolar proteases. Through analysis of the trafficking and degradation of Ctr1p mutants, two lysine residues in the C‐terminal cytoplasmic tail of Ctr1p, Lys340 and Lys345, were found to be critical for copper‐dependent endocytosis and degradation. In response to copper addition, Ctr1p was found to be ubiquitylated and a mutation in the Rsp5 ubiquitin ligase largely abolished ubiquitylation, endocytosis and degradation. In a strain lacking the Rsp5p accessory factors Bul1p and Bul2p, endocytosis and degradation of Ctr1p–green fluorescent protein were substantially diminished. Surprisingly, a Ctr1p mutant that lacks Lys340 and Lys345 was still ubiquitylated in a copper‐dependent manner, indicating that ubiquitylation of Ctr1p on other sites is insufficient to drive copper‐dependent endocytosis and degradation. This study demonstrates that copper regulates turnover of Ctr1p by stimulating Rsp5p‐dependent endocytosis and degradation of Ctr1p in the vacuole.
Analysis of appositional bone formation using a novel rat experimental model
Authors: Nakajima D , Kamakura S , Nakamura M , Suzuki O , Echigo S , Sasano Y
Published: July 2007

Aim:  To analyze the process of appositional bone formation using our original rat experimental model.

Materials and methods:  Rats were anesthetized and a ring made of polytetrafluorethylene was placed on the parietal bone surface in the surgical procedure. The time course of appositional bone formation was analyzed with histomorphometry and in situ hybridization for type I collagen and bone sialoprotein.

Results:  The rat experimental model allowed new bone to be formed on the pre‐existing bone surface and persist for 12 weeks. We demonstrated that bone is apposed actively for the first 4 weeks and less actively thereafter.

Conclusions:  The experimental model may contribute to biological analysis for appositional bone formation expected to occur in clinical procedures such as alveolar bone augmentation and sinus lifting.
Neurosyphilis presenting as psychiatric symptoms: an unusual case report
Authors: Mirsal Hasan , Kalyoncu Ayhan , Pektaş Özkan , Beyazyürek Mansur
Published: July 2007

Objective:

Neurosyphilis remains a differential diagnosis for a wide variety of psychiatric syndromes, including dementia, mood disorders and psychosis. However, the incidence of neurosyphilis presenting initially with psychiatric symptomalogy is unclear. In this article, a clinical case is reported so as to illustrate some of the issues involved.

Case presentation:

A 33-year-old married man was admitted because of a depressive episode associated with somatic preoccupations and a gradual loss of ability to function a year prior to his admission. The symptoms described above raised the question of an organic brain syndrome associated with the psychotic depression. Some laboratory and additional examinations were performed. Serological tests for syphilis were positive for both the hemagglutination test, Treponema pallidum hemaglutination (TPHA), and the immunofluorescent antibody test, fluorescent treponemal antibody-absorption (FTA-ABS). Based on these findings, the diagnosis of neurosyphilis was made. The patient was treated with benzathine penicillin (2 400 000 units i.m. once a week) for 3 weeks and venlafaxine (150 mg daily) and olanzapine (5 mg daily). His depression disappeared gradually, and he was discharged in partial remission.

Conclusion:

High-risk groups such as patients with neuropsychiatric diseases should be screened with serological tests so as to prevent morbidity and help eliminate syphilis.
Three‐dimensional facial morphology following surgical repair of unilateral cleft lip and palate in patients after nasoalveolar molding
Authors: Singh GD , Levy‐Bercowski D , Yáñez MA , Santiago PE
Published: July 2007

Structured Abstract

Authors –  Singh GD, Levy‐Bercowski D, Yáñez MA, Santiago PE

Objective –  To evaluate three‐dimensional (3D) facial morphology in patients surgically corrected for unilateral cleft lip and palate (UCLP) following pre‐surgical nasoalveolar molding (NAM).

Design –  Prospective, longitudinal study. Digital stereophotogrammetry was used to capture 3D facial images, and x, y, and z coordinates of five landmarks were digitized to compute mean morphologies. The sample comprised 15 patients with left UCLP and 10 matched control subjects. Facial form differences at age 37 weeks, using principal components analysis and finite‐element scaling analysis (FESA) were assessed.

Results –  Using the first two principal components, which accounted for 63% of the total shape‐change, UCLP and control groups showed similar distributions in the modal space (p > 0.05). For the UCLP group, the mean 3D facial form was smaller and less protrusive when superimposed on the non‐cleft mean. Using FESA, reductions in facial volume were found in the UCLP group, involving the columella (29%), labial tubercle (51%), lower lip (29%) and lateral aspects of the face (19%). The UCLP group also showed increases in size above the tip of the nose (25%) and laterally to the columella directly below the nares (29%).

Conclusions –  Following surgical repair of UCLP in patients previously treated with NAM, 3D facial morphology was virtually indistinguishable from the non‐cleft mean. Clinically, the apparent improvement in the facial soft tissues may mask dysmorphic skeletal growth, and further studies are required to characterize the underlying bony changes associated with the soft tissue changes reported here.
Review of the etiologic heterogeneity of the oculo‐auriculo‐vertebral spectrum (Hemifacial Microsomia)*
Authors: Hartsfield JK
Published: July 2007

Structured Abstract

Author –  James K. Hartsfield

Hemifacial microsomia is a congenital asymmetry of the lower face that may be associated with other cranial and extracranial anomalies. The variability of its severity, and wide range of anomalies that have been reported with it in some cases has resulted in these composite manifestations being given a number of names, including oculo‐auriculo‐vertebral spectrum (OAVS). Etiology is often stated to be a perturbation of embryonic blood flow in the developing region, although other factors may also play a role in some cases. Depending on what is considered to be minimum criteria for affected classification, what is often to be presumed to be a sporadic event in a family may be the more severe manifestation of a familial condition. Etiological factors are clearly heterogeneous, the investigation of which is confounded by not only the lack of a refined affected phenotype, but also the apparent influence of genetic factors in some instances that directly influence phenotype perhaps through alteration of mesodermal development, or indirectly through increased susceptibility to vascular disruption. Future studies likely to advance knowledge in this area will need to incorporate an analysis of who may be minimally affected in families, so that advances in genotyping will have greater power to distinguish genetic factors that may influence OVAS through interaction with environmental factors in particular families. The same genetic‐environmental factors and or etiological mechanisms may then be investigated in apparently sporadic cases.
A developmental approach to mental health for children and adolescents with orofacial clefts
Authors: Collett BR , Speltz ML
Published: July 2007

Structured Abstract

Authors –  Brent R. Collett, Matthew L. Speltz

The mental health of children, adolescents, and adults with orofacial clefts has been studied extensively. Outcomes of interest have included parental adaptation, parent–child attachment, child development, intellectual and academic outcomes, behavioral adaptation, and quality of life. The literature sheds light on mental health needs and opportunities in each of these domains at various stages of development. However, this research has been limited in several respects and methodologically rigorous studies are needed to clarify the role of mental health in craniofacial team care. In particular, randomized controlled trials investigating the efficacy of psychosocial interventions tailored for this population are long overdue. Such studies have the potential to advance routine mental health care for individuals with orofacial clefts to the level of ‘evidence‐based care.’
Genes affecting tooth morphogenesis
Authors: Kapadia H , Mues G , D'Souza R
Published: July 2007

Structured Abstract

Author –  Hitesh Kapadia, Gabriele Mues, Rena D’Souza

The development of dentition is a fascinating process that encompasses a complex series of epithelial–mesenchymal interactions involving growth factors, transcription factors, signal receptors and other soluble morphogens. It is not surprising that such a complex process is prone to disturbances and may result in tooth agenesis. Initial discoveries indicating that the homeo‐domain protein MSX1 and the paired‐domain transcription factor PAX9 are causative genes in tooth morphogenesis were made in mice. Both genes are co‐expressed in dental mesenchyme and either one, when homozygously deleted, results in an arrest at an early developmental stage. Heterozygous Pax9 or Msx1 mice have normal teeth, however, double heterozygous Pax9/Msx1 mice show a phenotype of arrested tooth development which can be rescued by transgenic expression of Bmp4, a very influential signaling factor in many developmental processes. We have obtained mounting evidence for a partnership between PAX9 and MSX1 within the tooth‐specific Bmp4 signaling pathway. In humans, unlike in mice, a heterozygous mutation in either PAX9 or MSX1 suffices to cause tooth agenesis of a predominantly molar or more premolar pattern, respectively. Our laboratory and others have identified several PAX9 and MSX1 mutations in families with non‐syndromic forms of autosomal dominant posterior tooth agenesis. We have also identified families with tooth agenesis in whom PAX9 and MSX1 mutations have been excluded opening up the possibilities for the discovery of other genes that contribute to human tooth agenesis.
Isolation and characterization of multipotent human periodontal ligament stem cells
Authors: Gay IC , Chen S , MacDougall M
Published: July 2007

Structured Abstract

Authors –  Gay IC, Chen S, MacDougall M

Backround –  Periodontal ligament (PDL) repair is thought to involve mesenchymal progenitor cells capable of forming fibroblasts, osteoblasts and cementoblasts. However, full characterization of PDL stem cell (SC) populations has not been achieved.

Objective –  To isolate and characterize PDLSC and assess their capability to differentiate into bone, cartilage and adipose tissue.

Methods –  Human PDL cells were stained for STRO‐1, FACS sorted and expanded in culture. Human bone marrow SC (BMSC) served as a positive control. PDLSC and BMSC were cultured using standard conditions conducive for osteogenic, chondrogenic and adipogenic differentiation. Osteogenic induction was assayed using alizarine red S staining and expression of alkaline phosphatase (ALP) and bone sialoprotein (BSP). Adipogenic induction was assayed using Oil Red O staining and the expression of PPARγ 2 (early) and LPL (late) adipogenic markers. Chondrogenic induction was assayed by collagen type II expression and toluidine blue staining.

Results –  Human PDL tissue contains about 27% STRO‐1 positive cells with 3% strongly positive. In osteogenic cultures ALP was observed by day‐7 in BMSC and day‐14 in PDLSC. BSP expression was detectable by day‐7; with more intense staining in PDLSC cultures. In adipogenic cultures both cell populations showed positive Oil Red O staining by day‐25 with PPARγ 2 and LPL expression. By day‐21, both BMSC and PDLSC chondrogenic induced cultures expressed collagen type II and glycosaminoglycans.

Conclusions –  The PDL contains SC that have the potential to differentiate into osteoblasts, chondrocytes and adipocytes, comparable with previously characterized BMSC. This adult PDLSC population can be utilized for potential therapeutic procedures related to PDL regeneration.
PC1/3, PC2 and PC5/6A are targeted to dense core secretory granules by a common mechanism
Authors: Dikeakos Jimmy D. , Mercure Chantal , Lacombe Marie‐Josée , Seidah Nabil G. , Reudelhuber Timothy L.
Published: July 2007

There are seven members of the proprotein convertase (PC) family of secreted serine proteases that cleave their substrates at basic amino acids, thereby activating a variety of hormones, growth factors, and viruses. PC1/3, PC2 and PC5/6A are the only members of the PC family that are targeted to dense core secretory granules, where they carry out the processing of proteins that are secreted from the cell in a regulated manner. Previous studies have identified α‐helices in the C‐termini of the PC1/3 and PC2 proteases that are required for this subcellular targeting. In the current study, we demonstrate that a predicted α‐helix in the C‐terminus of PC5/6A is also critical for the ability of this domain to target a heterologous protein to the regulated secretory pathway of mouse endocrine AtT‐20 cells. Analysis of the subcellular distribution of fusion proteins containing the C‐terminal domains of PC1/3, PC2 and PC5/6A confirmed that all three domains have the capacity to redirect a constitutively secreted protein to the granule‐containing cytoplasmic extensions. Analysis of the predicted structures formed by these three granule‐sorting helices shows a correlation between their granule‐sorting efficiency and the clustering of hydrophobic amino acids in their granule‐targeting helices.
The contribution of tryptophan residues to conformational changes in clostridial glutamate dehydrogenase − W64 and W449 as mediators of the cooperative response to glutamate
Authors: Hamza Muaawia A. , Martin Stephen R. , Engel Paul C.
Published: July 2007

The hexameric glutamate dehydrogenase of Clostridium symbiosum has previously been shown to undergo a pH‐dependent inactivating conformational change that perturbs the environment of one or more Trp residues and is reversed by glutamate in a highly cooperative fashion with a Hill coefficient of almost 6. Five single mutants have now been made in which each of the Trp residues in turn has been replaced by Phe. All five were successfully over‐produced as soluble proteins and purified. Far‐UV CD showed that none of the mutations significantly affected secondary structure. All five proteins were active, ranging from 13 U·mg−1 (W64F) to 20.8 U·mg−1 (W393F), compared to 20 U·mg−1 for wild‐type, and the kinetic parameters at pH 7 were little changed, except for a five‐ to six‐fold increase in Km for glutamate in W243F. Thermostability was also relatively little changed, although W310F and W393F were somewhat more stable and W64F less stable than the unmutated enzyme. All still showed the characteristic reversible, time‐dependent high‐pH inactivation. Near‐UV CD spectra, reflecting the environment of aromatic residues, were recorded at both pH 7 and 8.8, and four of the mutants showed essentially the same perturbation in the 280 nm region as the wild‐type enzyme. W64F, however, showed essentially no change. W64 is thus clearly a passive reporter of the pH‐dependent conformational change, and not actually required for the transition to occur. The CD comparisons also suggest that the aromatic CD spectrum is contributed almost entirely by W64 and W449. Consistent with the pH‐dependent change, all five mutant proteins also showed a positively cooperative response to glutamate at pH 9, reversing the inactivation. However, the Hill coefficient decreased from > 5 for wild‐type to approximately 3 for the active site cleft mutation W243F and to approximately 2 for the interfacial mutants W64F and W449F in which the trimer–trimer interaction may be directly interrupted. W64 of each subunit is in contact with W449 in its dimer partner at the trimer–trimer interface. It seems that, although neither of these two residues is required for the pH‐dependent change, together, they are essential in mediating the total cooperativity of the hexameric enzyme's response to glutamate and are presumably directly involved in transmitting conformational information between the two trimers.
Expression, post‐translational modification and biochemical characterization of proteins encoded by subgenomic mRNA8 of the severe acute respiratory syndrome coronavirus
Authors: Le Tra M. , Wong Hui H. , Tay Felicia P. L. , Fang Shouguo , Keng Choong‐Tat , Tan Yee J. , Liu Ding X.
Published: July 2007

The most striking difference between the subgenomic mRNA8 of severe acute respiratory syndrome coronavirus isolated from human and some animal species is the deletion of 29 nucleotides, resulting in splitting of a single ORF (ORF8) into two ORFs (ORF8a and ORF8b). ORF8a and ORF8b are predicted to encode two small proteins, 8a and 8b, and ORF8 a single protein, 8ab (a fusion form of 8a and 8b). To understand the functions of these proteins, we cloned cDNA fragments covering these ORFs into expression plasmids, and expressed the constructs in both in vitro and in vivo systems. Expression of a construct containing ORF8a and ORF8b generated only a single protein, 8a; no 8b protein expression was obtained. Expression of a construct containing ORF8 generated the 8ab fusion protein. Site‐directed mutagenesis and enzymatic treatment revealed that protein 8ab is modified by N‐linked glycosylation on the N81 residue and by ubiquitination. In the absence of the 8a region, protein 8b undergoes rapid degradation by proteasomes, and addition of proteasome inhibitors inhibits the degradation of protein 8b as well as the protein 8b‐induced rapid degradation of the severe acute respiratory syndrome coronavirus E protein. Glycosylation could also stabilize protein 8ab. More interestingly, the two proteins could bind to monoubiquitin and polyubiquitin, suggesting the potential involvement of these proteins in the pathogenesis of severe acute respiratory syndrome coronavirus.
Identification and characterization of plasma kallikrein–kinin system inhibitors from salivary glands of the blood‐sucking insect Triatoma infestans
Authors: Isawa Haruhiko , Orito Yuki , Jingushi Naruhiro , Iwanaga Siroh , Morita Akihiro , Chinzei Yasuo , Yuda Masao
Published: July 2007

Two plasma kallikrein–kinin system inhibitors in the salivary glands of the kissing bug Triatoma infestans, designated triafestin‐1 and triafestin‐2, have been identified and characterized. Reconstitution experiments showed that triafestin‐1 and triafestin‐2 inhibit the activation of the kallikrein–kinin system by inhibiting the reciprocal activation of factor XII and prekallikrein, and subsequent release of bradykinin. Binding analyses showed that triafestin‐1 and triafestin‐2 specifically interact with factor XII and high molecular weight kininogen in a Zn2+‐dependent manner, suggesting that they specifically recognize Zn2+‐induced conformational changes in factor XII and high molecular weight kininogen. Triafestin‐1 and triafestin‐2 also inhibit factor XII and high molecular weight kininogen binding to negatively charged surfaces. Furthermore, they interact with both the N‐terminus of factor XII and domain D5 of high molecular weight kininogen, which are the binding domains for biological activating surfaces. These results suggest that triafestin‐1 and triafestin‐2 inhibit activation of the kallikrein–kinin system by interfering with the association of factor XII and high molecular weight kininogen with biological activating surfaces, resulting in the inhibition of bradykinin release in an animal host during insect blood‐feeding.
Antimicrobial activity of silver‐containing dressings on wound microorganisms using an in vitro biofilm model
Authors: Percival Steven L , Bowler Phillip G , Dolman Jayne
Published: July 2007

Antimicrobial dressings such as those containing silver are now being used widely to control wound bioburden, and tests to demonstrate their efficacy predominantly involve in vitro models using free‐living or planktonic bacteria. In this present study a wide range of antibiotic‐sensitive and resistant bacteria were tested in their quasi‐sessile state using a standard agar assay and a second method used a poloxamer gel (true biofilm state – poloxamer encourages microorganisms to exhibit a more clinically relevant biofilm phenotype) technique. The antimicrobial activity of two silver dressings, a silver‐containing Hydrofiber® (SCH) dressing and a nanocrystalline silver‐containing dressing (NCS), were evaluated on a variety of microorganisms, using a zone‐of‐inhibition (ZOI) test. When grown on agar (presenting a quasi‐sessile state of each organism), the antibiotic‐susceptible microorganisms were generally more susceptible to the SCH dressing compared with the NCS. ZOIs associated with SCH dressing ranged between 5·7 and 17·5 mm; those for the NCS against the same group of organisms ranged between 1·9 and 8·6 mm. When grown on poloxamer gel, (presenting the biofilm state of each organism) the same group of microorganisms were less susceptible to both dressings. The SCH dressing was most effective against strains of Pseudomonas aeruginosa, Candida albicans and Staphylococcus aureus (ZOI range: 2·6–6 mm); the NCS was most effective against strains of Klebsiella pneumoniae, Enterococcus faecalis and Escherichia coli (i.e. ZOI range: 1–2·8 mm). Similarly to the antibiotic‐susceptible microorganisms, nine of ten antibiotic‐resistant bacterial strains when grown on agar were more susceptible to the SCH dressing compared with the NCS. Although the microorganisms tested were universally less susceptible to the silver dressings when in their biofilm state, in the majority of cases, the SCH dressing demonstrated greater biofilm‐inhibiting activity than the NCS.
Iodine revisited
Authors: Cooper Rose A
Published: July 2007

Iodine is an antiseptic that has been used in wound care for more than 150 years. Traditional formulations of iodine had serious limitations that were reduced in later products. Much has been written about iodine and opinions on its clinical efficacy are divided. There have been reviews of the chemical properties of iodine, its antimicrobial activity, human physiology, cytotoxicity and its clinical effectiveness, but few have addressed all these aspects. With the recent development of iodine‐containing wound care products and the continued publication of laboratory and clinical studies, it seems timely to reassess the evidence relating to the effectiveness of iodine for treating wounds. This literature review attempts to provide an appropriate chemical and physiological background of the characteristics of iodine in order to provide a sound basis for understanding the available microbiological and clinical data. It will show that understanding the factors that contribute to the activity and potential cytotoxicity of iodine are important in evaluating the clinical evidence. Although definitive studies are needed, the sustained delivery of low doses of free iodine offers the potential to inhibit a broad range of microbial species without selecting for resistant strains or inducing cytotoxic effects.
Comparative evaluation of silver‐containing antimicrobial dressings and drugs
Authors: Castellano Joseph J , Shafii Susan M , Ko Francis , Donate Guillermo , Wright Terry E , Mannari Rudolph J , Payne Wyatt G , Smith David J , Robson Martin C
Published: July 2007

Wound dressings containing silver as antimicrobial agents are available in various forms and formulations; however, little is understood concerning their comparative efficacy as antimicrobial agents. Eight commercially available silver‐containing dressings, Acticoat® 7, Acticoat® Moisture Control, Acticoat® Absorbent, Silvercel™, Aquacel® Ag, Contreet® F, Urgotol® SSD and Actisorb®, were tested to determine their comparative antimicrobial effectiveness in vitro and compared against three commercially available topical antimicrobial creams, a non treatment control, and a topical silver‐containing antimicrobial gel, Silvasorb®. Zone of inhibition and quantitative testing was performed by standard methods using Escherichia coli, Pseudomonas aeruginosa, Streptococcus faecalis and Staphylococcus aureus. Results showed all silver dressings and topical antimicrobials displayed antimicrobial activity. Silver‐containing dressings with the highest concentrations of silver exhibited the strongest bacterial inhibitive properties. Concreet® F and the Acticoat® dressings tended to have greater antimicrobial activity than did the others. Topical antimicrobial creams, including silver sulfadiazine, Sulfamylon and gentamicin sulfate, and the topical antimicrobial gel Silvasorb® exhibited superior bacterial inhibition and bactericidal properties, essentially eliminating all bacterial growth at 24 hours. Silver‐containing dressings are likely to provide a barrier to and treatment for infection; however, their bactericidal and bacteriostatic properties are inferior to commonly used topical antimicrobial agents.
How precise is the evaluation of chronic wounds by health care professionals?
Authors: Stremitzer Stefan , Wild Thomas , Hoelzenbein Thomas
Published: July 2007

Chronic wounds are a growing challenge for physicians and health insurance agencies. The burden of affected patients is enormous, because of pain but also because of long‐lasting therapies and dependence on nursing services. In other areas of medicine, computer‐based diagnostics is established, yet, accurate wound documentation is rarely conducted and is often limited to size measurement with a ruler and a rough photo documentation. Objective assessment of lesions by evaluation of granulation tissue, fibrin coverage and necrosis is not performed. The aim of this study was to investigate the spread and variety in judgement of a chronic wound. A diabetic ulcer was described by 16 wound therapists (eight physicians and eight nurses). Granulation tissue, fibrin coverage, necrosis, size and depth of the lesion, wound exudate and wound edges were judged, and the therapeutical consequences were determined. Study data show an extensive inhomogeneity and a wide spread of the results, like in no other field of medical diagnostics. This could be shown in the group of physicians, as well as in the group of nursing personnel. As the choice of treatment by a specialist is based upon the assessment of the wound, it is possible that in practice it can lead to suboptimal therapy. This is a consequence of varying treating physicians and subsequent changes in treatment regimens. This results in a prolongation of treatment and burden for the patient. Circumstances like this contribute to rising of costs in this area of the health care system. The goal is to apply objective wound diagnostic technologies in the field of chronic wounds to catch up with other diagnostic procedures.
Venous leg ulcers – the search for a prognostic indicator
Authors: Moore Keith , Huddleston Elizabeth , Stacey Michael C , Harding Keith G
Published: July 2007

Disordered cell function within chronic wounds generates many parameters that can be measured to differentiate between healing and non healing status. Theoretically, these may form the basis of a wound assessment system to define disease severity and response to treatment. In a review of tissue, wound exudate and microbiology studies of venous leg ulcers, we identify many such parameters that are associated with healing status. These include cytokines, proteases and their inhibitors, senescence markers, oxidative stress markers and microbiological status defined by culture. Some of these, such as protease level in wound exudate, have been proposed as prognostic indicators of healing status and many more could be considered potential markers to incorporate into a wound assessment system. However, no published data are available that validate known wound components to accurately reflect wound progression on a single patient basis. Rather than further characterisation of the expression of known wound biomarkers, the development of an accurate and objective test for prediction of chronic wound outcome requires identification of an appropriate combination of novel molecules that vary coordinately with healing status.
The cost of wound care for a local population in England
Authors: Drew Philip , Posnett John , Rusling Louise ,   Wound Care Audit Team
Published: July 2007

The objective of this study is to estimate the cost of wound care in a local population of approximately 590 000 using results from a wound care audit carried out in Hull and the East Riding of Yorkshire as a basis. Full results of the audit will be published separately. An audit in June 2005 provided information on patients with wounds and on their treatment. This was combined with representative National Health Service unit costs to produce an estimate of the total cost of wound care in 2005–2006. In all, 1644 patients had a total of 2300 wounds (1·44 per patient). Most (74·1%) were treated in the community by district nurses, 21·2% were treated in hospital and 4·8% were treated in residential or hospice care. More than one in four hospital inpatients (26·8%) had a wound. Median duration was 6–12 weeks. Twenty‐four per cent had their wound for 6 months or more, and almost 16% of patients had remained unhealed for a year or longer. One in eight wounds (12·8%) were reported as showing signs of infection. The estimated cost of wound care in 2005–2006 was £15 million to £18 million (£2·5 million to £3·1 million per 100 000 population). Caring for patients with wounds required the equivalent of 88·5 full‐time nurses and up to 87 hospital beds. Wounds are a significant source of cost to patients as well as the health care system. The most important determinant of cost appears to be wound complications which require hospitalisation or which delay hospital discharge. Reducing costs requires a systematic focus on effective and timely diagnosis, on ensuring treatment is appropriate to the cause and condition of the wound and on active measures to prevent complications and wound‐related hospitalisation. These results should be generalisable to other similar populations in the UK and elsewhere.