Cell and matrix response of temporomandibular cartilage to mechanical loading

OBJECTIVES: The generation of transgenic mice expressing green fluorescent proteins (GFPs) has greatly aided our understanding of the development of connective tissues such as bone and cartilage. Perturbation of a biological system such as the temporomandibular joint (TMJ) within its adaptive remodeling capacity is particularly useful in analyzing cellular lineage progression. The objectives of this study were to determine: (i) if GFP reporters expressed in the TMJ indicate the different stages of cell maturation in fibrocartilage and (ii) how mechanical loading affects cellular response in different regions of the cartilage. DESIGN/METHODS: Four-week-old transgenic mice harboring combinations of fluorescent reporters (Dkk3-eGFP, Col1a1(3.6 kb)-GFPcyan, Col1a1(3.6 kb)-GFPtpz, Col2a1-GFPcyan, and Col10a1-RFPcherry) were used to analyze the expression pattern of transgenes in the mandibular condylar cartilage (MCC). To study the effect of TMJ loading, animals were subjected to forced mouth opening with custom springs exerting 50 g force for 1 h/day for 5 days. Dynamic mineralization and cellular proliferation (EdU-labeling) were assessed in loaded vs control mice. RESULTS: Dkk3 expression was seen in the superficial zone of the MCC, followed by Col1 in the cartilage zone, Col2 in the prehypertrophic zone, and Col10 in the hypertrophic zone at and below the tidemark. TMJ loading increased expression of the GFP reporters and EdU-labeling of cells in the cartilage, resulting in a thickness increase of all layers of the cartilage. In addition, mineral apposition increased resulting in Col10 expression by unmineralized cells above the tidemark. CONCLUSION: The TMJ responded to static loading by forming thicker cartilage through adaptive remodeling

Dried fruit and public health – what does the evidence tell us?

A scientific workshop held in the UK explored the potential contribution of traditional dried fruits to public health, identified gaps in the evidence and addressed priorities for research. Presentations considered the categorisation and composition of dried fruits; dried fruit and gastrointestinal health; the polyphenol content of dried fruits and their potential contribution to health; dried fruit and appetite in relation to the psychology of snacking and obesity; dried fruit and dental health including its role as a snack; and conflicts in public health advice for dried fruits. A round table discussion explored the contribution of dried fruit to “five a day” fruit and vegetable intake and fibre intake, whether dried fruits have equivalence with fresh in terms of dietary advice, advice on snacking in relation to dental health and appetite control, informing the public about different types of dried fruits and avoiding consumer confusion, and future research requirements

Tumor-Targeted Delivery of IL-2 by NKG2D Leads to Accumulation of Antigen-Specific CD8+ T Cells in the Tumor Loci and Enhanced Anti-Tumor Effects

Interleukin-2 (IL-2) has been shown to promote tumor-specific T-cell proliferation and differentiation but systemic administration of IL-2 results in significant toxicity. Therefore, a strategy that can specifically deliver IL-2 to the tumor location may alleviate concerns of toxicity. Because NKG2D ligands have been shown to be highly expressed in many cancer cells but not in healthy cells, we reason that a chimeric protein consisting of NKG2D linked to IL-2 will lead to the specific targeting of IL-2 to the tumor location. Therefore, we created chimeric proteins consisting of NKG2D linked to Gaussia luciferase (GLuc; a marker protein) or IL-2 to form NKG2D-Fc-GLuc and NKG2D-Fc-IL2, respectively. We demonstrated that NKG2D linked to GLuc was able to deliver GLuc to the tumor location in vivo. Furthermore, we showed that TC-1 tumor-bearing mice intramuscularly injected with DNA encoding NKG2D-Fc-IL2, followed by electroporation, exhibited an increased number of luciferase-expressing E7-specific CD8+ T cells at the tumor location. More importantly, treatment with the DNA construct encoding NKG2D-Fc-IL2 significantly enhanced the therapeutic anti-tumor effects generated by intradermal vaccination with therapeutic HPV DNA in tumor-bearing mice. Therefore, by linking NKG2D to IL2, we are able to specifically deliver IL-2 to the tumor location, enhancing antigen-specific T-cell immune response and controlling tumor growth. Our approach represents a platform technology to specifically deliver proteins of interest to tumor loci

Characterization of a Drosophila Alzheimer's Disease Model: Pharmacological Rescue of Cognitive Defects

Transgenic models of Alzheimer's disease (AD) have made significant contributions to our understanding of AD pathogenesis, and are useful tools in the development of potential therapeutics. The fruit fly, Drosophila melanogaster, provides a genetically tractable, powerful system to study the biochemical, genetic, environmental, and behavioral aspects of complex human diseases, including AD. In an effort to model AD, we over-expressed human APP and BACE genes in the Drosophila central nervous system. Biochemical, neuroanatomical, and behavioral analyses indicate that these flies exhibit aspects of clinical AD neuropathology and symptomology. These include the generation of Aβ40 and Aβ42, the presence of amyloid aggregates, dramatic neuroanatomical changes, defects in motor reflex behavior, and defects in memory. In addition, these flies exhibit external morphological abnormalities. Treatment with a γ-secretase inhibitor suppressed these phenotypes. Further, all of these phenotypes are present within the first few days of adult fly life. Taken together these data demonstrate that this transgenic AD model can serve as a powerful tool for the identification of AD therapeutic interventions

Distribution of malocclusion types among thumb suckers seeking orthodontic treatment

The present study was conducted to evaluate the influence of thumb sucking and its duration on the type of malocclusion. A total of 410 North Indian individuals between ages 12-30 years, 161 males and 249 females were examined. A specially designed proforma was used to record the detailed history of the individual. Among the etiological factors it was found that history of thumb sucking was present in 13.9% and significantly related to Class II div 1 malocclusion. When thumb sucking exceeded 18 months, it was found statistically significant (P < 0.1) in Class II skeletal malocclusion, in open bite (P < 0.1) and in extreme overjet (P < 0.5). Conclusion: If thumb sucking is not treated early, it can cause skeletal Class II malocclusion, anterior open bite and excessive overjet

Early class III occlusal tendency in children and its selective management

Class III malocclusion may develop in children as a result of an inherent growth abnormality, i.e., true class III malocclusion, or as a result of premature occlusal contacts causing forward functional shift of the mandible, which is known as pseudo class III malocclusion. These cases, if not treated at the initial stage of development, interfere with normal growth of the skeletal bases and may result in severe facial deformities. The treatment should be carried out as early as possible with the aim of permitting normal growth. This paper deals with the selection of an appropriate treatment approach from the various current options available for early intervention in children developing class III occlusal tendencies; the different clinical features are depicted in the three case reports

Orthodontic movement of a maxillary central incisor with a horizontal root fracture treated using an intra-radicular fibre splint

This paper reports the case of a 15-year-old boy with a horizontal root fracture in the left maxillary central incisor along with class II division 1 malocclusion for whom a fixed orthodontic treatment was planned. The fracture was present at the junction of apical and middle-third as a result of trauma 2 years back. No splinting was carried out at that time and the tooth was found to be vital, asymptomatic and showed a type-1 repair pattern. An intentional root canal treatment was carried out for placement of an intra-radicular fiber splint, nearly 3 mm beyond the fracture line. Orthodontic treatment was initiated after a month; to which the fractured and splinted tooth responded successfully. This report highlights the successful use of an intra-radicular splint for horizontally fractured tooth requiring orthodontic treatment

Is tongue thrust that develops during orthodontic treatment an unrecognized potential road block?

The role of tongue thrust has often been suspected, long debated and largely dispelled as a primary etiological factor of malocclusion. However, tongue thrust may contribute to poor occlusal intercuspation both during and after treatment. A tongue thrust may also develop during orthodontic mechanotherapy as a result of the transient creation of intra and interarch spaces and this little recognized phenomenon was found to occur in many randomly followed cases. In many instances, this seemingly adaptive and secondary response of the tongue posture and function may persist and thereafter impede the resolution of intra and interarch problems