bluuebunny/crossref_metadata_2025 huggingface dataset:
Derivation of a novel undifferentiated human foetal phenotype in serum‐free cultures with BMP‐2
Authors: Mirmalek‐Sani Sayed‐Hadi , Stokes Paula J. , Tare Rahul S. , Ralph Esther J. , Inglis Stefanie , Hanley Neil A. , Houghton Franchesca D. , Oreffo Richard O.C.
Published: March 2009

Skeletal stem and progenitor populations provide a platform for cell‐based tissue regeneration strategies. Optimized conditions for ex vivo expansion will be critical and use of serum‐free culture may allow enhanced modelling of differentiation potential. Maintenance of human foetal femur‐derived cells in a chemically defined medium (CDM) with activin A and fibroblast growth factor‐2 generated a unique undifferentiated cell population in comparison to basal cultures, with significantly reduced amino acid depletion, appearance and turnover, reduced alkaline phosphatase (ALP) activity and loss of type I and II collagen expression demonstrated by fluorescence immunocytochemistry. Microarray analysis demonstrated up‐regulation of CLU, OSR2, POSTN and RABGAP1 and down‐regulation of differentiation‐associated genes CRYAB, CSRP1, EPAS1, GREM1, MT1X and SRGN as validated by quantitative real‐time polymerase chain reaction. Application of osteogenic conditions to CDM cultures demonstrated partial rescue of ALP activity. In contrast, the addition of bone morphogenetic protein‐2 (BMP‐2) resulted in reduced ALP levels, increased amino acid metabolism and, strikingly, a marked shift to a cobblestone‐like cellular morphology, with expression of SOX‐2 and SOX‐9 but not STRO‐1 as shown by immunocytochemistry, and significantly altered expression of metabolic genes (GFPT2, SC4MOL and SQLE), genes involved in morphogenesis (SOX15 and WIF1) and differentiation potential (C1orf19, CHSY‐2,DUSP6, HMGCS1 and PPL). These studies demonstrate the use of an intermediary foetal cellular model for differentiation studies in chemically defined conditions and indicate the in vitro reconstruction of the mesenchymal condensation phenotype in the presence of BMP‐2, with implications therein for rescue studies, screening assays and skeletal regeneration research.
Contribution of genetic factors for melanoma susceptibility in sporadic US melanoma patients
Authors: Laurin Council M. , Gardner Jennifer M. , Helms Cynthia , Liu Ying , Cornelius Lynn A. , Bowcock Anne M.
Published: March 2009

Abstract:  The risks of developing malignant melanoma (MM) include ultraviolet irradiation and genetic factors. To examine the contribution of rare and common variation within known MM genes in sporadic US MM patients, coding regions of known MM susceptibility genes [cyclin‐dependent kinase inhibitor 2A (CDKN2A), cyclin‐dependent kinase 4, melanocortin 1 receptor (MC1R) and tyrosinase (TYR)] were resequenced in 109–135 MM cases. The significance of variants was examined by comparing their frequencies in 390 cancer‐free controls. Potential deleterious mutations in CDKN2A were found in two patients and two others had variants of unknown significance. Cases were more likely than controls to harbour the MC1R‘R’ variants known or predicted to alter its function (P = 0.002), particularly the R160W variant (P = 0.0035). The associated TYR R402Q variant (rs1126809*A) was found in 29% of cases, similar to what has been described previously. One MM patient with a family history of MM, who had developed other skin cancers, was homozygous for a novel TYR variant (P406L) of unknown significance. Hence, rare variants in TYR may be important risk factors for skin cancer.
Alternatively activated macrophages (M2 macrophages) in the skin of patient with localized scleroderma
Authors: Higashi‐Kuwata Nobuyo , Makino Takamitsu , Inoue Yuji , Takeya Motohiro , Ihn Hironobu
Published: March 2009

Abstract:  Localized scleroderma is a connective tissue disorder that is limited to the skin and subcutaneous tissue. Macrophages have been reported to be particularly activated in patients with skin disease including systemic sclerosis and are potentially important sources for fibrosis‐inducing cytokines, such as transforming growth factor β. To clarify the features of immunohistochemical characterization of the immune cell infiltrates in localized scleroderma focusing on macrophages, skin biopsy specimens were analysed by immunohistochemistry. The number of cells stained with monoclonal antibodies, CD68, CD163 and CD204, was calculated. An evident macrophage infiltrate and increased number of alternatively activated macrophages (M2 macrophages) in their fibrotic areas were observed along with their severity of inflammation. This study revealed that alternatively activated macrophages (M2 macrophages) may be a potential source of fibrosis‐inducing cytokines in localized scleroderma, and may play a crucial role in the pathogenesis of localized scleroderma.
The tyrosine kinase network regulating mast cell activation
Authors: Gilfillan Alasdair M. , Rivera Juan
Published: March 2009

Summary:  Mast cell mediator release represents a pivotal event in the initiation of inflammatory reactions associated with allergic disorders. These responses follow antigen‐mediated aggregation of immunoglobulin E (IgE)‐occupied high‐affinity receptors for IgE (FcεRI) on the mast cell surface, a response which can be further enhanced following stem cell factor‐induced ligation of the mast cell growth factor receptor KIT (CD117). Activation of tyrosine kinases is central to the ability of both FcεRI and KIT to transmit downstream signaling events required for the regulation of mast cell activation. Whereas KIT possesses inherent tyrosine kinase activity, FcεRI requires the recruitment of Src family tyrosine kinases and Syk to control the early receptor‐proximal signaling events. The signaling pathways propagated by these tyrosine kinases can be further upregulated by the Tec kinase Bruton’s tyrosine kinase and downregulated by the actions of the tyrosine Src homology 2 domain‐containing phosphatase 1 (SHP‐1) and SHP‐2. In this review, we discuss the regulation and role of specific members of this tyrosine kinase network in KIT and FcεRI‐mediated mast cell activation.
PEST family phosphatases in immunity, autoimmunity, and autoinflammatory disorders
Authors: Veillette André , Rhee Inmoo , Souza Cleiton Martins , Davidson Dominique
Published: March 2009

Summary:  The proline‐, glutamic acid‐, serine‐ and threonine‐rich (PEST) family of protein tyrosine phosphatases (PTPs) includes proline‐enriched phosphatase (PEP)/lymphoid tyrosine phosphatase (LYP), PTP‐PEST, and PTP‐hematopoietic stem cell fraction (HSCF). PEP/LYP is a potent inhibitor of T‐cell activation, principally by suppressing the activity of Src family protein tyrosine kinases (PTKs). This function seems to be dependent, at least in part, on the ability of PEP to bind C‐terminal Src kinase (Csk), a PTK also involved in inactivating Src kinases. Interestingly, a polymorphism of LYP in humans (R620W) is a significant risk factor for autoimmune diseases including type 1 diabetes, rheumatoid arthritis, and lupus. The R620W mutation may be a ‘gain‐of‐function’ mutation. In non‐hematopoietic cells, PTP‐PEST is a critical regulator of adhesion and migration. This effect correlates with the aptitude of PTP‐PEST to dephosphorylate cytoskeletal proteins such as Cas, focal adhesion associated‐kinase (FAK), Pyk2, and PSTPIP. While not established, a similar function may also exist in immune cells. Additionally, overexpression studies provided an indication that PTP‐PEST may be a negative regulator of lymphocyte activation. Interestingly, mutations in a PTP‐PEST‐ and PTP‐HSCF‐interacting protein, PSTPIP1, were identified in humans with pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome and familial recurrent arthritis, two autoinflammatory diseases. These mutations abrogate the ability of PSTPIP1 to bind PTP‐PEST and PTP‐HSCF, suggesting that these two PTPs may be negative regulators of inflammation.
CARMA1‐mediated NF‐κB and JNK activation in lymphocytes
Authors: Blonska Marzenna , Lin Xin
Published: March 2009

Summary:  Activation of transcription factor nuclear factor‐κB (NF‐κB) and Jun N‐terminal kinase (JNK) play the pivotal roles in regulation of lymphocyte activation and proliferation. Deregulation of these signaling pathways leads to inappropriate immune response and contributes to the development of leukemia/lymphoma. The scaffold protein CARMA1 [caspase‐recruitment domain (CARD) membrane‐associated guanylate kinase (MAGUK) protein 1] has a central role in regulation of NF‐κB and the JNK2/c‐Jun complex in both B and T lymphocytes. During last several years, tremendous work has been done to reveal the mechanism by which CARMA1 and its signaling partners, B cell CLL‐lymphoma 10 and mucosa‐associated lymphoid tissue 1, are activated and mediate NF‐κB and JNK activation. In this review, we summarize our findings in revealing the roles of CARMA1 in the NF‐κB and JNK signaling pathways in the context of recent advances in this field.
Janus kinases in immune cell signaling
Authors: Ghoreschi Kamran , Laurence Arian , O’Shea John J.
Published: March 2009

Summary:  The Janus family kinases (Jaks), Jak1, Jak2, Jak3, and Tyk2, form one subgroup of the non‐receptor protein tyrosine kinases. They are involved in cell growth, survival, development, and differentiation of a variety of cells but are critically important for immune cells and hematopoietic cells. Data from experimental mice and clinical observations have unraveled multiple signaling events mediated by Jaks in innate and adaptive immunity. Deficiency of Jak3 or Tyk2 results in defined clinical disorders, which are also evident in mouse models. A striking phenotype associated with inactivating Jak3 mutations is severe combined immunodeficiency syndrome, whereas mutation of Tyk2 results in another primary immunodeficiency termed autosomal recessive hyperimmunoglobulin E syndrome. By contrast, complete deletion of Jak1 or Jak2 in the mouse are not compatible with life and, unsurprisingly, do not have counterparts in human disease. However, activating mutations of each of the Jaks are found in association with malignant transformation, the most common being gain‐of‐function mutations of Jak2 in polycythemia vera and other myeloproliferative disorders. Our existing knowledge on Jak signaling pathways and fundamental work on their biochemical structure and intracellular interactions allow us to develop new strategies for controlling autoimmune diseases or malignancies by developing selective Jak inhibitors, which are now coming into clinical use. Despite the fact that Jaks were discovered only a little more than a decade ago, at the time of writing there are 20 clinical trials underway testing the safety and efficacy of Jak inhibitors.
Multiple roles of Lyn kinase in myeloid cell signaling and function
Authors: Scapini Patrizia , Pereira Shalini , Zhang Hong , Lowell Clifford A.
Published: March 2009

Summary:  Lyn is an Src family kinase present in B lymphocytes and myeloid cells. In these cell types, Lyn establishes signaling thresholds by acting as both a positive and a negative modulator of a variety of signaling responses and effector functions. Lyn deficiency in mice results in the development of myeloproliferation and autoimmunity. The latter has been attributed to the hyper‐reactivity of Lyn‐deficient B cells due to the unique role of Lyn in downmodulating B‐cell receptor activation, mainly through phosphorylation of inhibitory molecules and receptors. Myeloproliferation results, on the other hand, from the enhanced sensitivity of Lyn‐deficient progenitors to a number of colony‐stimulating factors (CSFs). The hyper‐sensitivity to myeloid growth factors may also be secondary to poor inhibitory receptor phosphorylation, leading to impaired recruitment/activation of tyrosine phosphatases and reduced downmodulation of CSF signaling responses. Despite these observations, the overall role of Lyn in the modulation of myeloid cell effector functions is much less well understood, as often both positive and negative roles of this kinase have been reported. In this review, we discuss the current knowledge of the duplicitous nature of Lyn in the modulation of myeloid cell signaling and function.
SHP‐1 and SHP‐2 in T cells: two phosphatases functioning at many levels
Authors: Lorenz Ulrike
Published: March 2009

Summary:  Tyrosine phosphorylation and dephosphorylation of proteins play a critical role for many T‐cell functions. The opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) determine the level of tyrosine phosphorylation at any time. It is well accepted that PTKs are essential during T‐cell signaling; however, the role and importance of PTPs are much less known and appreciated. Both transmembrane and cytoplasmic tyrosine phosphatases have been identified in T cells and shown to regulate T‐cell responses. This review focuses on the roles of the two cytoplasmic PTPs, the Src‐homology 2 domain (SH2)‐containing SHP‐1 and SHP‐2, in T‐cell signaling, development, differentiation, and function.
Serum melatonin levels in adolescent idiopathic scoliosis prediction and prevention for curve progression – a prospective study
Authors: Machida Masafumi , Dubousset Jean , Yamada Thoru , Kimura Jun
Published: March 2009

Abstract:  The correlation of serum melatonin levels and curve progression in adolescent idiopathic scoliosis, and the effects of melatonin therapy in scoliotic patients with reduced levels of endogenous melatonin were studied in 40 adolescent patients with moderate to severe idiopathic scoliosis. Of the scoliotic subjects, 28 had stable scoliosis and 12 had progressive scoliosis. Normal melatonin levels were derived from 25 age‐matched control patients. Serum melatonin levels were monitored yearly in scoloiotic patients for a period ranging from 3 to 6 yr, revealing a diurnal pattern with low values during the day and high at night. Scoliotic patients with normal levels were not treated or were treated with a brace, and all but two patients with low endogenous melatonin were treated with oral supplements of the indole. Of the 22 patients with a normal melatonin level, 16 had stable scoliosis and six had progressive scoliosis. Of the 16 patients treated for a low melatonin level, 12 had stable scoliosis and four had a progressive course. The two untreated cases had a progressive course. Of the 12 patients who had progressive scoliosis, nine had >35° of curve at initial examination. These findings suggest that melatonin deficiency plays a role in the prognosis of idiopathic scoliosis. Therefore, melatonin supplements may prevent the progression of scoliosis, especially in mild cases with less than a 35° curve.
Integrated treatment to resolve a horizontal root fracture
Authors: Brandini Daniela Atili , Poi Wilson Roberto , Panzarini Sônia Regina , Sonoda Celso Koogi , De Castro José Carlos Monteiro , Luvizuto Eloá Rodrigues , Leal Cláudia Resende
Published: March 2009

Abstract –  Root fractures are defined as those that involve cement, dentin and pulp, comprising from 0.5 to 7% of injuries in permanent dentition. Diagnosis is made through clinical and radiographic exams, the latter frequently being limited by the position of the fracture. Treatment varies according to the displacement and vitality of the fragments. The authors present a clinical case of recurrent trauma of tooth 21 causing a horizontal root fracture in the middle third. After several attempts at endodontic treatment, the option was to remove the apical fragment by surgery. The postoperative period of 4 years shows very satisfactory results with regard to wound repair and tooth mobility, or implantation of the coronal segment.
Parasymphyseal fracture associated with fracture of a maxillary primary molar in a child: case report
Authors: Abdelnur Juliana Pires , Da Rosa Götze Gabriela , Barreira Alice Kelly , Maia Lucianne Cople
Published: March 2009

Abstract –  Bone and posterior tooth fractures can be serious injuries that are difficult to diagnose, particularly in emergencies. The aim of this study was to report a case of a parasymphyseal fracture associated with the fracture of a maxillary primary molar in a child.
Biocompatibility evaluation of alendronate paste in rat’s subcutaneous tissue
Authors: Mori Graziela Garrido , De Moraes Ivaldo Gomes , Nunes Daniele Clapes , Castilho Lithiene Ribeiro , Poi Wilson Roberto , Capaldi Maria Luciana P Manzoli
Published: March 2009

Abstract –  Alendronate is a known inhibitor of root resorption and the development of alendronate paste would enhance its utilization as intracanal medication. Therefore, this study aimed to investigate the biocompatibility of experimental alendronate paste in subcutaneous tissue of rats, for utilization in teeth susceptible to root resorption. The study was conducted on 15 male rats, weighing ∼180–200 grams. The rats’ dorsal regions were submitted to one incision on the median region and, laterally to the incision, the subcutaneous tissue was raised and gently dissected for introduction of two tubes, in each rat. The tubes were sealed at one end with gutta‐percha and taken as control. The tubes were filled with experimental alendronate paste. The animals were killed at 7, 15 and 45 days after surgery and the specimens were processed in laboratory. The histological sections were stained with hematoxylin‐eosin and analyzed by light microscopy. Scores were assigned to the inflammatory process and statistically compared by the Tukey test (P < 0.05). Alendronate paste promoted severe inflammation process at 7 days, with statistically significant difference compared to the control (P < 0.05%). However, at 15 days, there was a regression of inflammation and the presence of connective tissue with collagen fibers, fibroblasts and blood vessels was observed. After 45 days, it was observed the presence of well‐organized connective tissue, with collagen fibers and fibroblasts, and few inflammatory cells. No statistical difference was observed between the control and experimental paste at 15 and 45 days. The experimental alendronate paste was considered biocompatible with subcutaneous tissue of rat.
Traumatic anterior dental injuries in 7‐ to 12‐year‐old Brazilian children
Authors: Cavalcanti Alessandro Leite , Bezerra Priscilla Kelly Medeiros , De Alencar Catarina Ribeiro Barros , Moura Cristiano
Published: March 2009

Abstract –  The aim of this study was to determine the prevalence and risk factors of dental trauma in the permanent anterior teeth of schoolchildren in Campina Grande, Brazil. A sample of 448 schoolchildren, 228 boys and 220 girls, aged 7–12 years, were randomly selected from 17 public schools in an urban area. The sample selection was carried out in two stages: first, schools were selected by simple sampling and then children were chosen using a proportionality coefficient. Data were collected through clinical examinations and interviews, after examiner calibration. Overjet (OJ) was considered a risk factor when it presented values higher than 3 mm, while lip coverage was classified as adequate or inadequate. Yates’ chi‐squared test verified the association between the variables and odds ratio. Significance level was set at 5%. The prevalence of dental injuries was 21%. Boys experienced more injuries than girls, 21.9% and 20%, respectively (P > 0.05). Falls and collisions were the main causes of dental trauma, 63.8% and 24.5%, respectively. There was a statistically significant difference between traumatic dental injuries (TDI) and OJ (95% CI 0.22–0.63) (P < 0.001) and between TDI and inadequate lip coverage (95% CI 9.16–34.93) (P < 0.001). Data indicated that boys presenting an OJ size >3 mm and inadequate lip coverage were more likely to have TDI in Campina Grande, Brazil.
Maxillofacial fractures sustained during baseball and softball
Authors: Yamamoto Kazuhiko , Murakami Kazuhiro , Sugiura Tsutomu , Ishida Jun‐ichi , Imai Yuichiro , Fujimoto Masaki , Kirita Tadaaki
Published: March 2009

Abstract –  Aim:  The purpose of this study was to investigate the demographics, the type of impact, the site and the treatment of maxillofacial fractures sustained during baseball and softball to develop an effective preventive strategy.

Patients and methods:  Data of 82 patients treated for baseball‐ and softball‐related maxillofacial fractures at the Department of Oral and Maxillofacial Surgery, Nara Medical University between 1982 and 2007 were retrospectively analyzed.

Results:  Injuries were found in 64 men in baseball and 16 men and two women in softball with average ages of 19.6 and 30.0 years, respectively. Fractures were caused by being hit by the ball in 61 patients followed by collision in 16 patients. Fractures of the mandible and the mid‐face were found in 44 and 38 patients, respectively. The mental and angle region of the mandible and zygoma and alveolar bone of the maxilla were frequently involved. Treatment was mostly conservative. Open reduction and internal fixation were performed only in 15 patients.

Conclusions:  Most maxillofacial fractures in these sports were ball‐related. Therefore, effective preventive means should be considered to protect against such injuries.
Dental trauma in adults in Switzerland
Authors: Brunner Flavio , Krastl Gabriel , Filippi Andreas
Published: March 2009

Abstract –  Most epidemiologic studies of dental trauma are restricted to children and sports. The goal of the present study was to collect information on dental trauma in as many Swiss adults as possible. For that purpose data of the largest insurance company of Switzerland (SUVA) were evaluated and compared for the years 1992 and 2002. In these 2 years 23 000 dental injuries were reported to all insurance companies in Switzerland. Most often the upper central incisors were injured. However, in 20% posterior teeth were also affected. In 1992 most of the dental trauma was experienced by 30–39 year olds, in 2002 by 40–49 year olds. Regardless of the year, most of the injuries occurred at home; more than one‐fifth of the injuries were sports related. Most common injuries were crown fractures without pulp involvement. In less than 10% of all cases more complicated injuries like avulsions or crown‐root fractures occurred. Most traumatic injuries were treated by direct fillings and custom‐made crowns; more involved treatments were required less often. Comparison of the years 1992 and 2002 showed that the numbers of and causes for injuries had hardly changed in these 10 years. However, the choice of therapy was related to the general development of dental medicine, which became especially apparent in the fields of adhesive dentistry and implantology.
Prevalence of dental trauma in deciduous teeth of Brazilian children
Authors: Ferreira Jainara Maria Soares , Fernandes de Andrade Ednara Mércia , Katz Cíntia Regina Tornisiello , Rosenblatt Aronita
Published: March 2009

Abstract –  The aim of this study was to assess the prevalence of dental trauma as compared to the prevalence of dental caries in children aged 3–59 months. A cross‐sectional study was carried out during the National Immunization Day for Polio in Recife, northeast Brazil. The sample comprised 3489 children under the age of 5. The clinical examination was performed by 123 previously trained dental students. The inter‐examiner agreement for crown fracture was 90.32% and for tooth discoloration it was 83.87%. The prevalence of dental caries was assessed using the dmf‐t index. The statistical methods included descriptive analysis and the chi‐square test with a margin of error of 5%. A total of 56 142 teeth were examined and the prevalence of dental trauma was 14.9%. Dental fracture was the most prevalent injury observed in 516 teeth (0.9%), followed by discoloration in 191 (0.9%), intrusion in 12 (0.02%) and extrusion in five (0.008%). The most affected teeth were the upper central incisors. The prevalence of dental trauma increased significantly with age and family income (P < 0.0001). Dental trauma was most prevalent from 2 to 5 years of age. The prevalence of dental caries was 14.3%. This prevalence increased significantly with age (P < 0.0001) and with the reduction in family income (P < 0.0001). The results showed that the prevalence of dental caries and dental trauma was similar, and that both caused the same amount of damage to dental health for the target population.
Effect of calcium hydroxide‐based materials on periapical tissue healing and orthodontic root resorption of endodontically treated teeth in dogs
Authors: De Souza Ricardo Sampaio , De Souza Valdir , Holland Roberto , Gomes‐Filho João Eduardo , Murata Sueli Satomi , Sonoda Celso Koogi
Published: March 2009

Abstract –  This study evaluated periapical tissue healing and orthodontic root resorption of endodontically treated teeth sealed with calcium hydroxide in dogs. The sample consisted of three contralateral pairs of maxillary incisors and two contralateral pairs of mandibular incisors in each of two dogs using a split mouth design. After biomechanical preparation of the teeth in the first group (n = 10), a Ca(OH)2 dressing was placed for 14 days before root canal filling with Ca(OH)2‐based sealer (Sealapex) and gutta‐percha points. In the second group (n = 10), root canals were obturated immediately after the mechanical preparation with gutta‐percha points and zinc oxide and eugenol (ZOE)‐based sealer (Endofill). After completion of endodontic treatment, the teeth were moved with an orthodontic appliance with a calibrated force of 200 g, reactivated every 21 days. After 105 days, the animals were killed and the teeth were removed upon completion of active treatment, without a period of recovery, and prepared for histomorphological analysis. All sections of each tooth were graded subjectively on a scale from one to four to obtain the average of the 16 histomorphological parameters analysed. Evaluation of the differences between the two treatment protocols was made with Mann–Whitney U‐test. It was observed that the teeth treated with Ca(OH)2‐based materials provided better outcomes (P = 5%), with complete repair of all root resorption areas, high rate of biological closure of the main canal and apical accessory canals by newly formed cementum, less intense and extensive chronic inflammatory infiltrate, and better organization of the periodontal ligament. Under the tested conditions, Ca(OH)2‐based materials had a favourable action on periapical tissue healing and repair of orthodontic root resorption in endodontically treated dogs’ teeth.
Splinting duration and periodontal outcomes for replanted avulsed teeth: a systematic review
Authors: Hinckfuss Susan Elisabeth , Messer Louise Brearley
Published: March 2009

Abstract –  Clinical guidelines are now available for the management of avulsed teeth. The principles of evidence‐based dentistry can be used to assess whether these guidelines are based on currently‐available evidence. A qualitative systematic review was conducted of relevant clinical literature to examine the evidence on splinting duration and periodontal healing outcomes. The review was constrained markedly by small sample sizes, retrospective nature of clinical audits, dissimilarities of selected studies in their design, methodology and observation periods, and lack of uniformity in terminology for outcomes. A total of 138 replanted avulsed permanent teeth pooled from four papers each reporting both short‐term splinting (14 days or less) and long‐term splinting (over 14 days) in accord with current clinical guidelines, were studied. The evidence for an association between short‐term splinting and an increased likelihood of functional periodontal healing, acceptable healing, or decreased development of replacement resorption, appears inconclusive. The study found no evidence to contraindicate the current guidelines and suggests that the likelihood of successful periodontal healing after replantation is unaffected by splinting duration. Pending future research to the contrary, it is recommended that dentists continue to use the currently‐recommended splinting periods when replanting avulsed permanent teeth.
Bisphosphonate‐related jaw necrosis: A team approach management and prevention
Authors: Rayman S , Almas K , Dincer E
Published: March 2009

Abstract:  Osteonecrosis means the process of bone death. Bisphosphonates (BPs) are becoming recognized increasingly as having a significant impact on dental treatments. BPs are the most widely used class of anti‐resorptive drugs. They prevent bone resorption through osteoclast inhibition and are considered the standard of care for the management of metastatic bone disease. BPs are used for the treatment of skeletal disorders such as osteoporosis, hypercalcaemia of malignancy, ostoelytic lesions arising from solid tumours and Paget’s disease, breast cancer or prostate cancer. Jaw necrosis appears to be associated with the intravenous (i.v.) use of BPs. The aim of this review paper is to update the understanding of healthcare professionals to the osteonecrosis of jaws, mechanism of action and classification of BPs, management of the patients with BP‐related osteonecrosis (BRON) of the jaws. An interdisciplinary approach has been emphasized to prevent and manage the condition. Finally, the role of dental practitioners including dental hygienists has been discussed to early diagnose the BRON and improve the quality of life of patients with the condition.
Dentist–assistant interaction styles in Jordan
Authors: Khader YS , Abu‐Sharbain G
Published: March 2009

Abstract:  Objectives:  To assess dentist–assistant interaction and communication styles and their associated factors in Jordan.

Methods:  Three different areas in Amman where private dental clinics heavily cluster were chosen. The researcher visited all dental clinics in these areas and invited dentists to participate in this study. A structured self‐administered questionnaire was designed and included the 22 items on staff communication that were used by Gorter and Freeman to assess communication styles. The culturally adapted items were analysed in such a way to reflect the structure that is used in the original study.

Results:  There was a significant interaction between dentist’s gender and communication styles (F = 3.8, P = 0.022). The only significant difference between men and women was for professional leadership style (P = 0.011) where men were more likely to adopt professional leadership style than women. For men, the average score for friendly leadership style was significantly lower than that for other styles. For women, the average score was the highest for gender interacting style which was significantly higher than that for friendly leadership style and professional interacting style, but not business leadership style.

Conclusions:  Communication and interaction styles between Jordanian dentists and their assistants differ according to gender. Jordanian dentists are less likely to adopt friendly leadership communication style compared with other styles.
An individually tailored treatment programme for improved oral hygiene: introduction of a new course of action in health education for patients with periodontitis
Authors: Jönsson B , Öhrn K , Oscarson N , Lindberg P
Published: March 2009

Abstract:  Objectives:  To describe and evaluate an individually tailored treatment programme based on a behavioural medicine approach to oral hygiene self‐care for patients with chronic periodontitis.

Methods:  Two experimental single‐case studies with multiple‐baseline design across different self‐administered oral hygiene behaviours were conducted. Cognitive Behavioural techniques were used to organize the strategies for the intervention and the approach to counselling was inspired by and structured in accordance with Motivational Interviewing. The central features in the programme were the individual analysis of knowledge and oral hygiene habits, individually set goals for oral hygiene behaviour, practice of manual dexterity for oral hygiene aids, continuous self‐monitoring of the behaviour and prevention of relapse.

Results:  Both participants reached the predecided criteria for clinical significance in reducing plaque and bleeding on probing. Reductions of periodontal probing depth were achieved as well. The positive results remained stable throughout the 2‐year study period.

Conclusion:  The successful application of this educational model suggests that it could be used as a method for tailoring interventions targeted to oral hygiene for patients with periodontal conditions. The programme will now be tested in a larger randomized controlled trial.
Low U1 snRNP dependence at the NF1 exon 29 donor splice site
Authors: Raponi Michela , Buratti Emanuele , Dassie Elisa , Upadhyaya Meena , Baralle Diana
Published: March 2009

Many disease‐causing splicing mutations described in the literature produce changes in splice sites (SS) or in exon‐regulatory sequences. The delineation of these splice aberrations can provide important insights into novel regulation mechanisms. In this study, we evaluated the effect of patient variations in neurofibromatosis type 1 (NF1) exon 29 and its 5′SS surrounding area on its splicing process. Only two of all nonsense, missense, synonymous and intronic variations analyzed in this study clearly altered exon 29 inclusion/exclusion levels. In particular, the intronic mutation +5g>a had the strongest effect, resulting in total exon exclusion. This finding prompted us to evaluate the exon 29 5′SS in relation to its ability to bind U1 snRNP. This was performed by direct analysis of the ability of U1 to bind to wild‐type and mutant donor sites, by engineering an in vitro splicing system to directly evaluate the functional importance of U1 snRNA base pairing with the exon 29 donor site, and by coexpression of mutant U1 snRNP molecules to try to rescue exon 29 inclusion in vivo. The results revealed a low dependency on the presence of U1 snRNP, and suggest that exon 29 donor site definition may depend on alternative mechanisms of 5′SS recognition.
NMR studies on the interaction of sugars with the C‐terminal domain of an R‐type lectin from the earthworm Lumbricus terrestris
Authors: Hemmi Hikaru , Kuno Atsushi , Ito Shigeyasu , Suzuki Ryuichiro , Hasegawa Tsunemi , Hirabayashi Jun
Published: March 2009

The R‐type lectin EW29, isolated from the earthworm Lumbricus terrestris, consists of two homologous domains (14 500 Da) showing 27% identity with each other. The C‐terminal domain (Ch; C‐half) of EW29 (EW29Ch) has two sugar‐binding sites in subdomains α and γ, and the protein uses these sugar‐binding sites for its function as a single‐domain‐type hemagglutinin. In order to determine the sugar‐binding ability and specificity for each of the two sugar‐binding sites in EW29Ch, ligand‐induced chemical‐shift changes in EW29Ch were monitored using 1H–15N HSQC spectra as a function of increasing concentrations of lactose, melibiose, d‐galactose, methyl α‐d‐galactopyranoside and methyl β‐d‐galactopyranoside. Shift perturbation patterns for well‐resolved resonances confirmed that all of these sugars associated independently with the two sugar‐binding sites of EW29Ch. NMR titration experiments showed that the sugar‐binding site in subdomain α had a slow or intermediate exchange regime on the chemical‐shift timescale (Kd = 10−2 to 10−1 mm), whereas that in subdomain γ had a fast exchange regime for these sugars (Kd = 2–6 mm). Thus, our results suggest that the two sugar‐binding sites of EW29Ch in the same molecule retain its hemagglutinating activity, but this activity is 10‐fold lower than that of the whole protein because EW29Ch has two sugar‐binding sites in the same molecule, one of which has a weak binding mode.
Probing the substrate specificities of matriptase, matriptase‐2, hepsin and DESC1 with internally quenched fluorescent peptides
Authors: Béliveau François , Désilets Antoine , Leduc Richard
Published: March 2009

Type II transmembrane serine proteases are an emerging class of proteolytic enzymes involved in tissue homeostasis and a number of human disorders such as cancer. To better define the biochemical functions of a subset of these proteases, we compared the enzymatic properties of matriptase, matriptase‐2, hepsin and DESC1 using a series of internally quenched fluorogenic peptide substrates containing o‐aminobenzoyl and 3‐nitro‐tyrosine. We based the sequence of the peptides on the P4 to P4′ activation sequence of matriptase (RQAR‐VVGG). Positions P4, P3, P2 and P1′ were substituted with nonpolar (Ala, Leu), aromatic (Tyr), acid (Glu) and basic (Arg) amino acids, whereas P1 was fixed to Arg. Of the four type II transmembrane serine proteases studied, matriptase‐2 was the most promiscuous, and matriptase was the most discriminating, with a distinct specificity for Arg residues at P4, P3 and P2. DESC1 had a preference similar to that of matriptase, but with a propensity for small nonpolar amino acids (Ala) at P1′. Hepsin shared similarities with matriptase and DESC1, but was markedly more permissive at P2. Matriptase‐2 manifested broader specificities, as well as substrate inhibition, for selective internally quenched fluorescent substrates. Lastly, we found that antithrombin III has robust inhibitory properties toward matriptase, matriptase‐2, hepsin and DESC1, whereas plasminogen activator inhibitor‐1 and α2‐antiplasmin inhibited matriptase‐2, hepsin and DESC1, and to a much lesser extent, matriptase. In summary, our studies revealed that these enzymes have distinct substrate preferences.
Evaluation of the quality and cost‐effectiveness of Versajet® hydrosurgery
Authors: Sainsbury David CG
Published: March 2009

Judicious resource allocation to maximise benefits is essential to health care decision‐making, particularly with increasingly expensive treatments and rising populations. Accurate wound debridement is important, and while many methods exist, surgical debridement is currently the gold standard with material costs at approximately £140. Versajet®, a hydrosurgical device, is suggested by some to have facilitated a paradigm shift in wound management by allowing debridement of undesirable tissue while accurately preserving viable structures. Its proponents claim that it minimises surgical duration, length of hospital admission, improves wound healing and may be deployed at the bedside or in the community. Consoles and single‐use hand‐units cost £6000–£7000 and £220–£240, respectively. Some propose that hydrosurgery may provide an efficacious, efficient and cost‐effective alterative to surgical debridement. However, the evidence available is largely based on expert opinion. Methodological flaws of such descriptive studies include the lack of control groups, selection bias and lack of blinding. Hence, these claims need to be interpreted cautiously. This opinion review examines the available evidence as to whether Versajet hydrosurgery provides quality and cost‐effective care.
Intralesional administration of epidermal growth factor‐based formulation (Heberprot‐P) in chronic diabetic foot ulcer: treatment up to complete wound closure
Authors: Fernández‐Montequín José I , Betancourt Blas Y , Leyva‐Gonzalez Gisselle , Mola Ernesto L , Galán‐Naranjo Katia , Ramírez‐Navas Mayte , Bermúdez‐Rojas Sergio , Rosales Felix , García‐Iglesias Elizeth , Berlanga‐Acosta Jorge , Silva‐Rodriguez Ricardo , Garcia‐Siverio Marianela , Martinez Luis H
Published: March 2009

Previous studies have shown that an epidermal growth factor‐based formulation (Heberprot‐P) can enhance granulation of high‐grade diabetic foot ulcers (DFU). The aim of this study was to explore the clinical effects of this administration up to complete wound closure. A pilot study in 20 diabetic patients with full‐thickness lower extremity ulcers of more than 4 weeks of evolution was performed. Mean ulcer size was 16·3 ± 21·3 cm2. Intralesional injections of 75 μg of Heberprot‐P three times per week were given up to complete wound healing. Full granulation response was achieved in all 20 patients in 23·6 ± 3·8 days. Complete wound closure was obtained in 17 (85%) cases in 44·3 ± 8·9 days. Amputation was not necessary in any case and only one relapse was notified. The most frequent adverse events were tremors, chills, pain and ardour at site of administration and local infection. The therapeutic scheme of intralesional Heberprot‐P administration up to complete closure can be safe and suitable to improve the therapeutic goal in terms of healing of chronic DFU.
Behavioural and Toxic Interaction Profile of Ketamine in Combination with Caffeine
Authors: Hsu Hui‐Ru , Mei Yung‐Yu , Wu Chia‐Yen , Chiu Pao‐Hsiang , Chen Hwei‐Hsien
Published: March 2009

Abstract: Ketamine street tablets often contain several other compounds in addition to ketamine, among them is caffeine. The purpose of this study was to examine whether caffeine interacts with ketamine‐induced behavioural and toxic effects. Male ICR mice were treated with ketamine alone or ketamine combined with various doses of caffeine, then the locomotor activity, rotarod test, prepulse inhibition of acoustic startle, loss of righting reflex, and mortality rate were examined. Caffeine enhanced the locomotor hyperactivity, caused disruption of the rotarod performance, and mortality rates due to ketamine, whereas prepulse inhibition deficits and anaesthesia remained unaffected. These findings demonstrate that use of ketamine in combination with caffeine enhances its stimulant responses and lethal risk, suggesting that a potentially toxic interaction exists between ketamine and caffeine.
Hepatitis Caused by Lotus‐f3?
Authors: Bergman Jenny , Schjøtt Jan
Published: March 2009

Abstract:  We present a case of hepatitis and jaundice are associated with ingestion of Lotus‐f3 submitted to our regional pharmacovigilance centre. A 56‐year‐old woman with psoriatic arthritis developed increased liver enzymes and jaundice 3 weeks after having started to take the product. The woman had been treated with etanercept for more than a year. She was hospitalized with hepatitis, and viral causes were ruled out. Liver biopsy suggested autoimmune or toxic hepatitis. Both etanercept and Lotus‐f3 were withdrawn, and 6 weeks later the liver enzymes were normalized without any treatment. Etanercept was subsequently successfully reintroduced, and based on the rapid resolution of the hepatitis, a toxic effect of Lotus‐f3 was suggested. This was the first report in the national adverse drug reaction database for this product, but three similar cases have now been reported. Lotus‐f3 contains an extract of green tea, which has been associated with hepatotoxicity. The Norwegian adverse drug reaction database contains nine reports of hepatitis or jaundice associated with natural products. Four different natural products containing extracts of green tea have been suspected in eight out of these nine reports.
Rational Design of Multitargeted Tyrosine Kinase Inhibitors: A Novel Approach
Authors: Barchéchath Sylvie , Williams Christopher , Saade Khalil , Lauwagie Sylvia , Jean‐Claude Bertrand
Published: March 2009

The non‐receptor Src tyrosine kinase is known to cooperate with the epidermal growth factor receptor in a mechanism leading to invasion and metastasis of solid tumours. With the purpose of developing agents targeted to both epidermal growth factor receptor and Src or related kinases, we embarked on the design of chimeric molecules termed combi‐molecules capable of blocking both Src and epidermal growth factor receptor. To this end, we have chosen to design molecules containing a quinazoline moiety (directed at epidermal growth factor receptor) and a 7‐phenyl‐pyrazolopyrimidine (directed at Src). Molecular modelling showed that the optimal position to attach the linker was the 6‐position of the quinazoline and the 9‐position of the pyrazolopyrimidine. This has led to the synthesis of SB162, SB166 and SB163. SB163 containing the longest linker was the only molecule capable of inducing a dose‐dependent inhibition of both Src and epidermal growth factor receptor. SB163 also induced a dose inhibition of Abl and PDGFR.
Three‐Dimensional Quantitative Structure–Activity Relationship Studies on c‐Src Inhibitors Based on Different Docking Methods
Authors: Bairy Santhosh Kumar , B. V. S Suneel Kumar , Bhalla Joseph Uday Tej , Pramod A. B. , Ravikumar Muttineni
Published: March 2009

c‐Src kinase play an important role in cell growth and differentiation and its inhibitors can be useful for the treatment of various diseases, including cancer, osteoporosis, and metastatic bone disease. Three dimensional quantitative structure–activity relationship (3D‐QSAR) studies were carried out on quinazolin derivatives inhibiting c‐Src kinase. Molecular field analysis (MFA) models with four different alignment techniques, namely, glide, gold, ligandfit and Least squares based methods were developed. glide based MFA model showed better results (Leave one out cross validation correlation coefficient r2cv= 0.923 and non‐cross validation correlation coefficient r2 = 0.958) when compared with other models. These results help us to understand the nature of descriptors required for activity of these compounds and thereby provide guidelines to design novel and potent c‐Src kinase inhibitors.
Modulation of rabbit sinoatrial node activation sequence by acetylcholine and isoproterenol investigated with optical mapping technique
Authors: Abramochkin D. V. , Kuzmin V. S. , Sukhova G. S. , Rosenshtraukh L. V.
Published: March 2009

Aims: Changes in the rabbit sinoatrial node (SAN) activation sequence with the cholinergic and adrenergic factors were studied. The correlation between the sinus rhythm rate and the leading pacemaker site shift was determined. The hypothesis concerning the cholinergic suppression of nodal cell excitability as one of the mechanisms associated with pacemaker shift was tested.

Methods: A high‐resolution optical mapping technique was used to register beat‐to‐beat changes in the SAN activation pattern under the influence of the cholinergic and adrenergic factors.

Results: Acetylcholine (10 μm) and strong intramural parasympathetic nerve stimulation caused a pacemaker shift as well as rhythmic slowing and the formation of an inexcitable region in the central part of SAN. In this region the generation of action potentials was suppressed. The slowing of the sinus rhythm (which exceeded 12.8 ± 3.1% of the rhythm control rate) always accompanied the pacemaker shift. Isoproterenol (10, 100 nm, 1 μm) and sympathetic postganglionic nerve stimulation also evoked a pacemaker shift but without formation of an inexcitable zone. The acceleration of the sinus rhythm, which exceeded 10.5 ± 1.3% of the control rate of the rhythm, always accompanied the shift.

Conclusions: Both cholinergic and adrenergic factors cause pacemaker shifts in the rabbit SAN. While modest changes in the sinus rhythm do not coincide with the pacemaker shift, greater changes always accompany the shift and may be caused by it, according to one hypothesis. The formation of an inexcitable zone at the place where the leading pacemaker is situated is one of the mechanisms associated with pacemaker shift.
Identification, Characterization, and Function of a Novel Oncogene
Authors: JORDÀ MERITXELL ALBERICH , RAYMAN NAZIK , VALK PETER , De WEE EVA , DELWEL RUUD
Published: March 2009

Abstract:By means of retroviral insertional mutagenesis, we identified a novel common virus integration site (cVIS) (Evi11) in murine leukemias, and demonstrated that Cb2, encoding the peripheral cannabinoid receptor, is the potential proto‐oncogene located in that region. Cb2 is a 7‐transmembrane G protein‐coupled receptor (GPCR), which is normally expressed on B lymphocytes. Using transwell assays we observed strong migration of Cb2‐expressing cells upon stimulation with 2‐arachidonoylglycerol (2‐AG), a potent endocannabinoid. Overexpression of Cb2 receptor on murine myeloid precursor cells causes a block of neutrophilic differentiation, a major characteristic of myeloid leukemia. Intriguingly, we could not detect functional Cb2 receptors on normal murine bone marrow precursor cells. Furthermore, analysis of human acute myeloid leukemia (AML) samples revealed the presence of CB2 mRNA transcripts in several cases. Furthermore, migration could be induced by 2‐AG when analyzed in one of the patient samples. Our data suggest that the initially identified cVIS, Evi11, encodes for a murine onco‐protein and that human CB2 may be involved in certain cases of human AML as well.