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Localized scleroderma (LoS) or morphea is a rare group of inflammatory disorders resulting in excessive collagen deposition and subsequent sclerosis of the skin and subdermal tissues. Linear scleroderma (LiS) or linear morphea is the most common subtype of LoS in children and primarily affects the face and extremities. This case report details the three-year follow-up of a five-year-old girl with LiS of the left upper lip and adjacent oral mucosal tissue. She also presented with a concurrent developmental root defect of the permanent maxillary left central incisor. Intralesional corticosteroids were considered as a first-line treatment; however, parents declined it. Decision was made to biopsy when the lesion showed signs of progression. At subsequent reviews, the affected mucosal surface appeared to have stabilized but progressive notching of the upper lip was noted. In the long term, after cessation of disease activity, the patient will require aesthetic intervention to surgically correct her upper lip.

Objectives The purpose of the study was to retrospectively investigate the prevalence, location, orientation, origin and height of the maxillary sinus septa as well as the location of anastomosis (of the infra-orbital artery and posterior superior alveolar artery) from the alveolar crest in a sample population of Singapore. Methods The study was done through the retrospective analysis of cone beam computed tomography (CBCT) images of 224 maxillary sinuses in 139 patients. Results The prevalence of septa was 38.3% in this study. Septa formation was most commonly seen at the anterior region (i.e. first and second premolar), followed by the posterior (third molar) and middle region (first and second molar). 93% of the septa demonstrated a bucco-lingual orientation. 61.6% of septa were found to be primary septa i.e. located above root apices of maxillary teeth whereas 38.4% of septa were secondary septa i.e. located above an edentulous span. The mean height of the septa was 5.95 mm. The intra-osseous anastomosis between the infra-orbital artery and posterior superior alveolar artery was visible on the coronal view of 100 (45%) maxillary sinuses and the mean height of the intra-osseous anastomosis from the alveolar crest was 17.8 mm. Conclusion To prevent the occurrence of complications, it is vital to have sufficient pre-operative knowledge of the possible anatomic structures present in the maxillary sinus. Having pre-operative CBCT imaging prior to sinus augmentation is advantageous as it allows for accurate assessment for the presence of septa or other anatomic irregularities that may complicate the surgery.

The prefrontal cortex is essential for executive functions such as decision-making and planning. There is also accumulating evidence that it is important for the modulation of pain. In this study, we investigated a possible role of prefrontal cortical calcium-independent phospholipase A2 (iPLA2) in antinociception induced by the norepinephrine reuptake inhibitor (NRI) and tetracyclic (tricyclic) antidepressant, maprotiline. Intraperitoneal injections of maprotiline increased iPLA2 mRNA and protein expression in the prefrontal cortex. This treatment also reduced grooming responses to von-Frey hair stimulation of the face after facial carrageenan injection, indicating decreased sensitivity to pain. The antinociceptive effect of maprotiline was abrogated by iPLA2 antisense oligonucleotide injection to the prefrontal cortex, indicating a role of this enzyme in antinociception. In contrast, injection of iPLA2 antisense oligonucleotide to the somatosensory cortex did not reduce the antinociceptive effect of maprotiline. Lipidomic analysis of the prefrontal cortex showed decrease in phosphatidylcholine species, but increase in lysophosphatidylcholine species, indicating increased PLA2 activity, and release of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) after maprotiline treatment. Differences in sphingomyelin/ceramide were also detected. These changes were not observed in maprotiline-treated mice that received iPLA2 antisense oligonucleotide to the prefrontal cortex. Metabolites of DHA and EPA may help to strengthen a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate a role of prefrontal cortical iPLA2 and its enzymatic products in the antinociceptive effect of maprotiline.

The prefrontal cortex is essential for executive functions such as decision-making and planning. There is also accumulating evidence that it is important for the modulation of pain. In this study, we investigated a possible role of prefrontal cortical calcium-independent phospholipase A

Functional neuroimaging studies have implicated the prefrontal cortex (PFCTX) in descending modulation of pain and the placebo effect. This study was performed to elucidate comprehensive PFCTX gene expression in an animal model of persistent trigeminal pain. Adult male C57BL/6J mice received facial carrageenan injection and showed sustained increase in nociceptive responses. Microarray analyses of differentially expressed genes in the PFCTX at 3 d after injection showed “immune system process” as the dominant ontology term and increased mRNA expression ofS100a8,S100a9,Lcn2,Il2rg,Fcgr1,Fcgr2b,C1qb,Ptprc,Ccl12, andCd52were verified by RT-PCR. Upregulation of S100A8, S100A9, and lipocalin 2 (LCN2) were confirmed by Western blots, and cells in the PFCTX were double immunolabeled with MPO, indicating they were neutrophils. Analyses of blood of facial carrageenan-injected mice also showed increased mRNA expression of these markers, suggesting transmigration of activated neutrophils into the brain. Other immune-related genes,Il2rg,Fcgr2b,C1qb,Ptprc, andCcl12were upregulated in the PFCTX but not blood. Approximately 70% of S100A9-positive cells in the PFCTX of carrageenan-injected mice were located in capillaries adherent to endothelial cells, whereas 30% were within the brain parenchyma. Carrageenan-injected mice showed significantly reduced nociceptive responses after injection of C terminus of murine S100A9 protein in the lateral ventricles and PFCTX but not somatosensory barrel cortex. Together, these findings demonstrate activation of immune-related genes in the PFCTX during inflammatory pain and highlight an exciting role of neutrophils in linking peripheral inflammation with immune activation of the PFCTX and antinociception.

Recent studies suggest that CNS phospholipase A(2) (PLA(2) ) isoforms play a role in nociception, but until now, direct evidence of increased brain PLA(2) activity during allodynia or hyperalgesia is lacking. The present study was carried out, using lipidomics or systems wide analyses of lipids using tandem mass spectrometry, to elucidate possible changes in rat brain lipids after inflammatory pain induced by facial carrageenan injection. The caudal medulla oblongata showed decreases in phospholipids including phosphatidylethanolamine and phosphatidylinositol species, but increases in lysophospholipids, including lysophosphatidylethanolamine, lysophosphatidylinositol and lysophosphatidylserine, indicating increased PLA(2) activity and release of arachidonic acid after facial carrageenan injection. These changes likely occur in the spinal trigeminal nucleus which relays nociceptive input from the orofacial region. High levels of sPLA(2) -III, sPLA(2) -XIIA, cPLA(2) and iPLA(2) mRNA expression were detected in the medulla oblongata. Increase in sPLA(2) -III mRNA expression was found in the caudal medulla of carrageenan-injected rats, although no difference in sPLA(2) -III protein expression was detected. The changes in lipids as determined by lipidomics were therefore consistent with an increase in PLA(2) enzyme activity, but no change in enzyme protein expression. Together, these findings indicate enhanced PLA(2) activity in the caudal medulla oblongata after inflammatory orofacial pain.

Dental implant plays an important role as a conduit of force and stress to flow from the tooth to the related bone. In the load sharing between an implant and its related bone, the amount of stress carried by each of them directly related to their stiffness or modulus. Hence, it is a crucial issue for the implant to have matching mechanical properties, in particular modulus, between the implant and its related bone. Titanium is a metallic material that has good biocompatibility and corrosion resistance. Whilst the modulus of the bulk material is still higher than that of bone, it is the lowest among all other commonly used metallic implant materials, such as stainless steel or cobalt alloy. Hence it is potential to further reduce the modulus of pure Titanium by engineering its processing method to obtain porous structure. In this project, porous Titanium implant prototype is fabricated using 3-dimensional printing. This technique allows the flexibility of design customization, which is beneficial for implant fabrication as tailoring of implant size and shape helps to ensure the implant would fit nicely to the patient. The fabricated Titanium prototype had a modulus of 4.8—13.2 GPa, which is in the range of natural bone modulus. The compressive strength achieved was between 167 to 455 MPa. Subsequent cell culture study indicated that the porous Titanium prototype had good biocompatibility and is suitable for bone cell attachment and proliferation.

Secretory phospholipase A2 (sPLA2) activity is present in the CNS and the sPLA2-IIA isoform has been shown to induce exocytosis in cultured hippocampal neurons. However, little is known about possible contributions of various lysophospholipid species to exocytosis in neuroendocrine cells. This study was therefore carried out to examine the effects of several lysophospholipid species on exocytosis on rat pheochromocytoma-12 (PC12) cells. An increase in vesicle fusion, indicating exocytosis, was observed in PC12 cells after external infusion of lysophosphatidylinositol (LPI), but not lysophosphatidylcholine or lysophosphatidylserine by total internal reflection microscopy. Similarly, external infusion of LPI induced significant increases in capacitance, or number of spikes detected at amperometry, indicating exocytosis. Depletion of cholesterol by pre-incubation of cells with methyl beta cyclodextrin and depletion of Ca2+ by thapsigargin and incubation in zero external Ca2+ resulted in attenuation of LPI induced exocytosis, indicating that exocytosis was dependent on the integrity of lipid rafts and intracellular Ca2+. Moreover, LPI induced a rise in intracellular Ca2+ suggesting that this could be the trigger for exocytosis. It is postulated that LPI may be an active participant in sPLA2-mediated exocytosis in the CNS.

It was recently demonstrated that osteogenesis of hESC was more efficient without the initial embryoid body formation step. This study sought to further improve this direct differentiation culture system, by developing an autologous osteogenic-inducing culture supplement extracted from hESC-derived osteogenic cells themselves. A whole cell lysate was prepared from hESC-derived osteogenic cells, simply by exposure to deionized water followed by free-thawing and subsequent filtration. The product was used to coat the surface of cell culture dishes together with gelatin, prior to culture of hESC under osteogenic-inducing conditions. The results showed that the autologous cell lysate extract promoted the aggregation and clustering of cells to form nodule-like structures. Immunohistochemical staining on day 9 demonstrated that these cellular aggregates strongly expressed STRO-1, while on day 14 the nodule-like structures stained positively for both osteocalcin and osteonectin (SPARC). By contrast, the negative control (gelatin coating alone) showed much less prominent cellular aggregation and clustering, and was stained much less intensely for these markers. Additionally, Von Kossa staining on day 14 was also more intense in the presence of the autologous cell lysate extract. Hence, this product can be used to further enhance the osteogenesis of hESC. This would save costs from the use of highly-expensive cytokines, growth factors and matrix components, as well as avoid pathogenic transmission from animal and human products.

The objective of this study was to compare the osteogenic potential of human embryonic stem cells (hESCs) within two- and three-dimensional (2D and 3D) culture systems. hESCs of the H1 line (Wicell Inc., Madison, Wisc., USA) were induced to form embryoid bodies (EBs) through 5 days of suspension culture within non-adherent culture dishes. Following enzymatic dissociation, the EB-derived single cells were seeded on either novel 3D porous PLGA scaffolds or 2D culture dishes with the same total cell number. Osteogenic differentiation was induced through culture media supplemented with dexamethasone, L-ascorbic acid and beta-glycerophosphate. After 3 weeks of in vitro culture, quantitative and qualitative assays of osteogenic differentiation were conducted. Osteocalcin secretion and alkaline phosphatase (AP) activities were detected at significantly higher levels within 3D culture compared with the 2D system. Subsequently, the cell-scaffold constructs were implanted in iliac crest defects of immunosuppressed rabbits. After 4 weeks, the constructs were subsequently explanted and characterized by histology and X-ray analysis. Formation of new bone was detected within and around the implanted scaffolds. The results demonstrate that the osteogenic differentiation of human embryonic stem cells is enhanced in a 3D culture system compared to a 2D culture environment. Upon implantation in situ, the differentiating human embryonic stem cells can contribute positively to the repair and regeneration of bone defects.

When the Academy of Medicine was formed in 1957, Dr J A Jansen was as one of its dental founding members. As the membership strength of dental surgeons increases in the ensuing years, the Chapter of Dental Surgeons was officially formed within the Academy of Medicine, Singapore in 1979 with Dr Edmund Tay Mai Hiong as the first Chairman of the Dental Chapter Committee 1979-1980. Following upon the footsteps of Dr Edmund Tay, many prominent Dental Academicians from both Institutions and Private Sector had come forth to lead the Dental Chapter since then. The membership strength in the Dental chapter had grown steadily from 37 members in 1982 to the current number at 179 Fellows. Over the years, the Dental Chapter has continued to play a significant role in the continuing education of dental surgeons in general as well as influencing and contributing to the nurturing and development of dental specialties in Singapore. Key words: Chapter of Dental Surgeons, Dentistry, History

Increases in several ceramide species have been shown by non-targeted lipid profiling (lipidomics) of the rat hippocampus after kainate lesions (Guan et al. FASEB J 20:1152-1161, 2006). This study was carried out to examine possible effects of ceramide species on exocytosis. Significant increase in membrane capacitance in voltage-clamped rat pheochromocytoma (PC12) cells, an indication of exocytosis, was detected immediately after external application of C2, C6, and C18 ceramide. In contrast, no increase in capacitance was found after addition of C16 and C20 ceramide, or DMSO vehicle. The effect of ceramide on exocytosis was dependent on the integrity of lipid rafts. Treatment of cells with the cholesterol binding agent/disruptor of lipid rafts, methyl beta cyclodextrin, prior to addition of C18 ceramide suppressed the increase in capacitance induced by this lipid species. The ability of C2, C6 and C18 ceramide to trigger exocytosis was confirmed using total internal reflection fluorescence microscopy (TIRFM) experiments. External application of these species caused an exponential decrease in the number of subplasmalemmal neuropeptide Y (NPY)-enhanced green fluorescence protein (EGFP) labeled vesicles, indicating exocytosis. Interestingly, C18 is also the ceramide species that showed the greatest increase in the rat hippocampus after kainate excitotoxicity. It is postulated that C18 ceramide might facilitate exocytosis of glutamate from damaged neurons, thus propagating neuronal injury.

The present study was carried out to determine the effects of central nervous free fatty acids, lysophospholipids, or platelet activating factor (PAF), in a mouse facial carrageenan injection model of orofacial pain. Mice that received intracerebroventricular (I.C.V.) injection of arachidonic acid or oleic acid showed significantly reduced allodynia and behavioral responses to von Frey hair stimulation of a carrageenan-injected area of the face, at 8 h post-injection, compared to controls that received I.C.V. injection of vehicle. In contrast to free fatty acids, increased responses were observed in mice at 72 h after I.C.V. lysophosphatidic acid or lysophosphatidylcholine injection, and at 8 and 24 h after PAF injection, compared vehicle injected controls. Information regarding pro-nociceptive effect of specific brain lipids may be a useful basis for further studies to explore mechanism.

The present study was carried out to elucidate the distribution of calcium-independent phospholipase A(2) (iPLA(2)) in the normal monkey brain. iPLA(2) immunoreactivity was observed in structures derived from the telencephalon, including the cerebral neocortex, amygdala, hippocampus, caudate nucleus, putamen, and nucleus accumbens, whereas structures derived from the diencephalon, including the thalamus, hypothalamus and globus pallidus were lightly labeled. The midbrain, vestibular, trigeminal and inferior olivary nuclei, and the cerebellar cortex were densely labeled. Immunoreactivity was observed on the nuclear envelope of neurons, and dendrites and axon terminals at electron microscopy. Western blot analysis showed higher levels of iPLA(2) protein in the cytosolic, than the nuclear fraction, but little or no protein in the membrane fraction. Similarly, subcellular fractionation studies of iPLA(2) activity in rat brain cortical cell cultures showed greater enzymatic activity in the cytosolic, than the nuclear fraction, and the least activity in non-nuclear membranes. The association of iPLA(2) with the nuclear envelope suggests a role of the enzyme in nuclear signaling, such as during neuronal proliferation and differentiation or death. In addition, the localization of iPLA(2) in dendrites and axon terminals suggests a role of the enzyme in neuronal signaling.

The present study was carried out to elucidate the effect of a single episode of oxidative stress on pyramidal neurons of the rat hippocampus. A significant increase in the number of neurons that were immunolabeled for the toxic lipid peroxidation product, 4-hydroxynonenal (HNE) was observed in field CA3 of the hippocampus, at 1 day, 7 days and 14 days after intracerebroventricular injection of 1 μL of 5mM ferrous ammonium citrate, compared to ammonium citrate injected controls at these time points. The number of HNE positive cells was fewer at 14 days, compared to 1 day, after ferrous ammonium citrate injection. The changes in HNE imunoreactivity were paralleled by changes in cytoplasmic phospholipase A 2 (CPLA 2 ) labeling in the pyramidal neurons in adjacent sections, suggesting that some of the HNE could have arisen as a result of peroxidation of arachidonic acid that was released by cPLA 2 . Interestingly, despite the HNE and cPLA 2 labeling, no loss of neurons was observed in adjacent Nissl and Fluoro-Jade stained sections. Electron microscopy also showed that the HNE or cPLA 2 labeled cells had features of injured neurons, rather than necrotic neurons. The reduction of HNE immunoreactivity in neurons at 14 days after oxidative injury, and the absence of cell loss at any of the time intervals, shows that hippocampal pyramidal neurons have remarkable ability to recover from a single episode of oxidative stress, if repeated injury such as seizures / excitotoxicity could be avoided.

The present study was carried out, using inhibitors to secretory phospholipase A2 (sPLA2, 12-epi-scalaradial), cytosolic phospholipase A2 (cPLA2, AACOCF3), or calcium-independent phospholipase A2 (iPLA2, bromoenol lactone), to compare possible contributions of central nervous PLA2 isoforms to the development of allodynia after facial carrageenan injection in mice. C57BL/6J (B6) mice showed increased responses to facial stimulation using a von Frey hair (1 g force), at 8 h, 1 day, and 3 days after facial carrageenan injection. On the other hand, BALB/c mice did not show increased responses at any of the time points. In both B6 and BALB/c mice, intracerebroventricular injection of inhibitors to each of the three PLA2 isoforms significantly reduced responses to von Frey hair stimulation at 8 h and 1 day after facial carrageenan injection, but at 3 days after injection, only the sPLA2 inhibitor had an effect. Since BALB/c mice did not show increased responses after facial carrageenan injection, the reduction in responses actually indicates that there is loss of normal sensitivity to von Frey hair stimulation after intracerebroventricular injection of each of these inhibitors, in this strain of mice. The effects of PLA2 inhibitors are unlikely to be due simply to inhibition of arachidonic acid generation, since intracerebroventricular injection of arachidonic acid also had an anti-nociceptive effect. The above results support an important role of central nervous PLA2s in neurotransmission and pain transmission.

Although the synaptology, neural connectivity, and the roles played by nitric oxide (NO) and other neurotransmitters have been extensively studied in spinal pain, such information is rather scanty with respect to orofacial pain transmission. This paper presents the findings of several investigations carried out by the author and his colleagues on the roles of NO in orofacial pain transmission in male Wistar rats, using nicotinamide adenosine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry using light and electron microscopy; and NOS immunohistochemistry and immunofluorescence using both light and confocal laser scanning microscopy. The results revealed that (1) a complicated relation existed between the nitrergic axon terminals and dendrites in the caudal part of the spinal trigeminal nucleus (cSTN); (2) the nitrergic neuronal cells bodies were not projection neurons, but rather, local circuit neurons; (3) although the thalamus projecting neurons in the cSTN did not synthesize NO, they could be modulated by NO diffused from nitrergic neurons; (4) c-fos positive neurons in the superficial laminae of the cSTN, detected following subcutaneous injection of 0.5 ml of 4% formalin into the left lateral face of the rats, respond to the release of glutamate through activation of N-methyl-D-aspartate (NMDA), alpha-amine-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and metabotropic glutamate (mGlu) receptors expressed by these c-fos neurons; and (5) NO might play a seemingly less important role than glutamate in neural transmission.

We report a case of an asymptomatic sclerosing odontogenic tumor in a 31-year-old woman. Radiologically, the tumor was well circumscribed, was predominantly radiolucent, and had a peripheral sclerotic margin. Histopathologically, the tumor showed small clusters, strands, and cords of small to medium-sized epithelial tumor cells in a sclerotic collagenous stroma. Immunohistochemically, the tumor cells were positive for broad-spectrum cytokeratins (CKs) (CK7, CK5/6, CK19, and CAM 5.2) and p63. Membranous staining for E-cadherin was present. There was weak to moderate nuclear expression of p16 in 30% of cells. Rare tumor cells were positive for p53. Progesterone receptors were expressed in about 60% of the tumor cells. The proliferative activity (Ki-67) was approximately 2%. A molecular genetic (fluorescence in situ hybridization) study showed no EWSR1 (EWS RNA-binding protein 1) gene rearrangement. No recurrence or metastatic events have been documented at 1-year follow-up. This tumor represents a classification dilemma mainly between epithelial-rich central odontogenic fibroma and the so-called sclerosing odontogenic carcinoma.

This survey was undertaken to study the clinical features of trigeminal neuralgia in an Asian population. Demographic data of 44 patients treated at the Dental Faculty of the National University of Singapore and at the University of Malaya were reviewed. The results of the survey were analysed and comparisons made with those of Caucasian patients as reported in other studies where there was a general similarity in the clinical findings. Trigeminal neuralgia presented predominantly in females. Right-sided involvement occurred at a greater frequency, and the peak age at onset was between the sixth and seventh decades of life. The only significant variant in the present sample was the greater involvement of the mandibular branch of the trigeminal nerve rather than the maxillary division. In addition, there was a much greater representation from Chinese patients over Malays as compared with their ratios in the general population.

Medline, Embase and a variety of other sources were searched for English-language articles. Non-journal publications, conferences proceedings from professional organisations and from private and government agencies were screened. Bibliographies and reference lists from peer-reviewed and ‘grey’ literature were also reviewed. To meet the inclusion criteria articles must have reported studies of at least 10 patients, involve diagnoses of disc displacement with reduction (DDwR) or without reduction (DDw/oR) or degenerative joint disease (DJD) and include at least one of the following surgical techniques: arthrocentesis; arthroscopy; discectomy without replacement or disc repair/repositioning. The outcome measured was the proportion of patients who reported improvement after treatment. Study success rates were recalculated on an intent-to-treat basis. Meta-analyses were performed along with meta-regressions where heterogeneity was an issue. Three classes of meta-analyses were performed using different artificial, untreated, control groups assuming three levels of spontaneous improvement, namely 0, 37.5 and 75%. Twenty-two studies, comprising 30 patient groups and sample sizes of 11–237 patients, met the inclusion criteria. For studies of patients with DDwR, at the 0 and 37.5% rates of control group improvement, arthroscopy and disc repair/repositioning resulted in treatment effects significantly greater than zero, with no significant differences in the efficacy of these two surgical techniques. For studies of patients with DDw/OR, the proportion of patients who improved after arthroscopy or arthrocentesis was significantly greater than zero at all three levels of estimated control improvement. Disc repair effect size was not significant at the 75% rate. Surgical treatments appear to have some efficacy for people who have temporomandibular articular disorders that do not respond to nonsurgical therapies.

Background The innate immune response (IMR) is critical for the oral mucosa due to their continuous exposure to various oral pathogens. Keratinocytes play important role in IMR. Therefore, to date, keratinocytes from different sources have been used as in vitro research model for the study of IMR. However, current keratinocyte research models are hampered by the limited supply, patients' dependency and batch to batch variation. Therefore, in this study, we demonstrated the use of human embryonic stem cells (hESCs) derived keratinocytes (H9-Kert) as an alternative research model for the study of IMR. Methods The expression kinetics of toll-like receptor (TLR) 2, TLR 4, interleukin (IL) -6, IL-8, inducible nitric oxide synthase (iNOS) and tumour necrosis factor-alpha (TNF-α), in H9-Kert and immortalized human keratinocyte cell line (HaCaT) were analysed at mRNA levels by both reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR. The activation of the inflammatory transcription factor nuclear factor kappa-b (NFĸB) was assayed in these cells by transiently transfecting the cells with NFĸB reporter plasmid. Activation of NFĸB following treatment with heat-killed Porphyromonas gingivalis (P. gingivalis), an oral pathogen, was determined by assaying for the reporter, secreted alkaline phosphatase activity. Results The expression of TLRs, cytokines and activation of NFĸB following bacterial stimulation showed in both H9-Kert and the widely used HaCaT keratinocyte cell line was similar. Conclusion Overall, our results support the potential application of hESCs as an alternative limitless cell source for primary keratinocytes which can be used as consistent and dependable research tool with minimum variations and no donor's dependency.

Progression of diabetes-associated periodontal destruction and the roles of advanced glycation end products (AGEs) are investigated.Diabetes was induced by streptozocotin injection, and periodontitis was induced via silk ligature placement with Porphyromonas gingivalis lipopolysaccharide injection in 64 Sprague-Dawley rats for 7 to 21 days. The quality of alveolar bone and attachment loss (AL) were measured by microcomputed tomography and histology. Destruction profiles were evaluated by histology, histochemistry, immunohistochemistry, and quantitative assessments of inflammatory cells, expression of receptors for AGEs (RAGE), tartrate-resistant acid phosphatase, and proliferating cell nuclear antigen.Without periodontitis induction, there was no obvious morphologic change in the periodontium, although slight elevations of AGEs and RAGE levels were noted in animals with diabetes. In the group with experimental periodontitis, significant periodontal bone loss was noted in animals both with and without diabetes from day 7, with more progressive bone loss in animals with diabetes during days 14 to 21. Histologically, the disruption of attachment and inflammation were observed from day 7, but subsequently subsided in animals without diabetes. A stronger and more prolonged response with significant AL was observed in animals with diabetes. Stronger inflammation, attenuated and persistent resorptive activity, and weaker proliferating potential were demonstrated by animals with diabetes. AGE deposition and RAGE expression were noted in animals without diabetes but with periodontitis, although levels were considerably elevated in the later stages in animals with diabetes.Diabetes augments periodontal destruction by reducing the proliferating capability and activating resorptive activities. Presence of the AGE-RAGE axis without diabetes implies that it is involved in the regulation of inflammation.

This study was carried out to elucidate the effects of calcium independent phospholipase A(2) (iPLA(2)) on mitochondrial function and exocytosis in neuroendocrine cells. iPLA(2) mRNA and protein were detected in cell lysates and mitochondria from PC12 cells. Treatment of cells with the iPLA(2) inhibitor, bromoenol lactone (BEL), resulted in reduction in the mitochondrial membrane potential. Increase in membrane capacitance and number of spikes at amperometry, indicating exocytosis, were detected from PC12 cells after treatment with BEL. The induced exocytosis was abolished by pre-incubation of cells with the antioxidant, glutathione monoethyl ester, spin-trap/free radical scavenger, PBN, or inhibitors of the mitochondrial permeability transition pore, cyclosporine A and bongkrekic acid. These findings indicate that inhibition of iPLA(2) results in excessive exocytosis through increased oxidative damage (or failure to repair such damage) and defects in mitochondrial function. A similar process may occur in neurons with mutations in iPLA(2), leading to neuronal injury.

Activation of the prefrontal cortex occurs during acute and chronic pain and models of experimental hyperalgesia. The present study was carried out to determine possible miRNA changes in the prefrontal cortex, after inflammatory pain induced by facial carrageenan injection in mice. miRNA microarray analyses showed significantly increased levels of miR-155 and miR-223 in the prefrontal cortex of carrageenan-injected mice. The changes were verified by real-time RT-PCR, and shown to occur bilaterally. The potential targets of the two miRNAs were predicted, and changes in two of the miRNA targets, c/ebp Beta and granulocyte colony-stimulating factor (GCSF) verified by real-time RT-PCR. Significantly downregulated c/ebp Beta but upregulated GCSF, accompanied by increased immunolabeling with an antibody to myeloperoxidase were found in the prefrontal cortex of facial carrageenan treated mice. It is postulated that this could lead to increased inflammation and activation of the prefrontal cortex. Further studies are necessary to determine if specific miRNAs could be useful as therapeutic molecules for pain.

Phospholipases A(2) (PLA(2)) are enzymes which cleave the sn-2 ester bond in membrane phospholipids to release free fatty acids and lysophospholipids. The present study aimed to elucidate the expression profile of multiple secretory phospholipase A(2) (sPLA(2)) isoforms in the normal rat CNS with focus on sPLA(2)-IIA in the brainstem and spinal cord. Quantitative RT-PCR analysis showed that sPLA(2)-IB expression was low throughout the CNS, sPLA(2)-IIA expression was high in the brainstem and spinal cord, sPLA(2)-IIC expression was high in the cerebral neocortex, hippocampus and thalamus/hypothalamus, sPLA(2)-V expression was high in the olfactory bulb and cerebellum, and sPLA(2)-X was expressed at very low levels in the normal CNS. Of the isoforms, sPLA(2)-IIA mRNA expression was highest in the brainstem and spinal cord suggesting that this could be the most relevant isoform in the ascending pain pathway. Western blot analysis showed high level of sPLA(2)-IIA expression in the brainstem and cervical, thoracic and lumbar spinal segments but low level of expression in other parts of the brain. sPLA(2)-IIA was localized by immunohistochemistry to the spinal trigeminal and facial motor nuclei and dorsal- and ventral-horns of the spinal cord. The enzyme was found on the endoplasmic reticulum of neuronal cell bodies and small diameter dendrites or dendritic spines at electron microscopy. The expression of sPLA(2)-IIA in the dorsal horn and spinal trigeminal nucleus is consistent with previous results which showed an important role of CNS sPLA(2) in nociceptive transmission.

Utilizing a suitable combination of lactide and glycolide in a copolymer would optimize the degradation rate of a scaffold upon implantation in situ. Moreover, 3D printing technology enables customizing the shape of the scaffold to biometric data from CT and MRI scans. A previous in vitro study has shown that novel 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds had good biocompatibility and mechanical properties comparable with human cancellous bone, while they could support proliferation and osteogenic differentiation of osteoblasts. Based on the previous study, this study evaluated PLGA scaffolds for bone regeneration within a rabbit model. The scaffolds were implanted at two sites on the same animal, within the periosteum and within bi-cortical bone defects on the iliac crest. Subsequently, the efficacy of bone regeneration within the implanted scaffolds was evaluated at 4, 12 and 24 weeks post-surgery through histological analysis. In both the intra-periosteum and iliac bone defect models, the implanted scaffolds facilitated new bone tissue formation and maturation over the time course of 24 weeks, even though there was initially observed to be little tissue ingrowth within the scaffolds at 4 weeks post-surgery. Hence, the 3D-printed porous PLGA scaffolds investigated in this study displayed good biocompatibility and are osteoconductive in both the intra-periosteum and iliac bone defect models.

This was a retrospective study of dentigerous cysts in people from the Singapore-Malaysian region. The purpose of this study was to present the clinicopathologic features of dentigerous cysts in the Oriental population and to compare these data with those from other reported studies. Biopsy records from 1981 to 1993 of 119 cases of dentigerous cysts from patients in Malaysia and Singapore showed that 36.1% of patients were female and 63.9% patients were male. Among patients with cysts, 70.5% were Chinese, 23.2% were Malays, 2.7% were Indian and 3.6% were other ethnic groups. The mean age of these patients was 30.2 +/- 17.3 years with a peak incidence occurring in the second and third decades. The location of the lesions was almost equal to the maxilla (50.9%) and the mandible (49.1%). There was a marked predilection for the posterior mandible (42.7%) followed by the anterior maxilla (38.2%). Histologically, 90.8% of the cysts were lined by a non-keratinised stratified squamous epithelium. The cyst linings were mainly thin (90.0%) with 38.7% of cases having a mixed thick and thin lining. Mucous metaplasia was observed in 9 (7.6%) cases. Rushton bodies were seen in 3.4% of cases. Cholesterol clefts in the epithelial lining and lumen were found in 16.8% cases while 12.6% of cases exhibited cholesterol clefts in the cyst wall. Other cellular structures within the cyst wall were lymphocytes (66.4%), plasma cells (52.1%), Russell bodies (16.0%) and histiocytes (4.2%). Odontogenic keratocysts were observed in 5.0% of cases. One case of adenomatoid odontogenic tumour was also observed. Epithelial atypia was seen in 9.2% of cases, islands of stratified squamous epithelial cells in 8.4% of cases while one case showed a combination of these two features. In conclusion, some clinical features seen in this study are similar to that for the Caucasian population such as prevalence in male, peak incidence in the second and third decades and the predilection for the posterior mandible and anterior maxilla. Histopathologically, odontogenic keratocyst and adenomatoid odontogenic tumour were observed in dentigerous cysts.

The present study was carried out to examine global gene expression in the brainstem, in a mouse facial carrageenan injection model of orofacial pain. Mice that received facial carrageenan injection showed increased mechanical allodynia, demonstrated by increased responses to von Frey hair stimulation of the face. The brainstem was harvested at 3 days post-injection, corresponding to the time of peak responses, and analyzed by Affymetrix Mouse Genome 430 2.0 microarrays. We sought to identify common genes that are changed in the respective sides of the brainstem after either right- or left-sided facial carrageenan injection. The result is a relatively small list of genes (22 genes), which were then classified using DAVID software. Many of them fell into the categories of "response to stress", "defence response", "response to biotic stimulus", "cell adhesion" and "leukocyte adhesion". Of these, increased expression of P-selectin, ICAM-1 and CCL12 after carrageenan injection could be verified by real-time RT-PCR on both the right and left sides, and increased in P-selectin and ICAM-1 further verified by Western blot analysis. P-selectin and ICAM-1 were immunolocalized to endothelial cells, and were double labelled with von Willebrand factor. Intraperitoneal injection of the P-selectin inhibitor KF38789 significantly reduced mechanical allodynia in the facial carrageenan-injected mice. P-selectin mediates the capturing of leukocytes from the bloodstream and rolling of leukocytes along the endothelial surface. We hypothesize that increased nociceptive input to the brainstem could attract circulating macrophages into the brain, resulting in neuroinflammation and pain.

This was a retrospective study of odontogenic keratocysts in people from the Singapore-Malaysian region. The purpose of this study was to present the clinicopathologic features of odontogenic keratocysts in the Oriental population and to compare these data with those from other reported studies. Biopsy records from 1981 to 1992 of 61 cases of odontogenic keratocysts from patients in Malaysia and Singapore showed that 42.6% of patients were female and 57.4% of patients were male. Among patients with cysts, 75.4% were Chinese, 6.6% were Malays, 9.8% were Indians and 8.2% were other ethnic groups. The mean age of these patients was 26.98 +/- 15.38 years with a peak incidence occurring in the second to fourth decades. The location of the lesions was more often in the mandible (65.5%) than the maxilla (31.0%). There was a marked predilection for lesions to occur in the posterior mandible. Histologically, 90.2% of the cysts were lined with a para-keratinized stratified squamous epithelium while only 3.3% of the cysts were lined with orthokeratinized stratified squamous epithelium. Mixed para-keratinized and orthokeratinized epithelial linings were observed in 4 cases (6.5%). The cyst linings were mainly uninflamed (95.1%). Inflammation of the cyst wall was found in 42 cases (68.8%). Twelve (19.7%) cases contained keratin in the lumen. A satellite cyst was observed in only 6 cases (9.8%). In conclusion, most clinical and histological features seen in this study were similar to those found for Caucasians. The only clinical feature that was different was the peak age incidence, that ranged from the second to fourth decades, with an absence of a second peak. Odontogenic keratocysts presenting at the site of the dentigerous cyst were observed in 7 cases (11.5%).

Data sources Index Medicus, MEDLINE were searched, as well as the bibliographies of identified studies. Study selection Papers selected were those in which odontogenic keratocysts (OKC) was diagnosed histologically, the patient selection process was adequately described, there was consecutive, adequate description of the follow-up period, and where detailed treatment information and recurrence rates were included and assessed using eight defined criteria. Data extraction and synthesis The treatment method and recurrence rates were extracted and tabulated. Results Fourteen papers met the criteria. These were restricted to retrospective consecutive case-series. The type of treatment and recurrence rates are shown in the Table 1. Conclusions The literature is limited to retrospective study designs and prospective studies need to be initiated. It appears, however, that resection or enucleation with adjunctive therapy is associated with lower recurrence rates than enucleation alone.

A patient with chronic renal failure was investigated after complaining of oral discomfort which was found to be due to macroglossia and generalized involvement of the oral soft tissues by amyloidosis. A search for multiple myeloma proved to be positive. She also had a previous history of Carpal-tunnel syndrome. Despite an initial good response to treatment with phenylalanine nitrogen mustard (melphalan hydrochloride), she finally succumbed to end-stage renal failure.

Question: In patients who need oral surgery is it necessary to stop low-dose aspirin prior to treatment? Objective To assess the effect of low-dose aspirin on intra- and post-operative bleeding during oral surgery. Design Randomised controlled trial (RCT). Intervention Thirty-nine patients requiring oral surgery were randomised either to a control group where low-dose aspirin was stopped 7 days prior to treatment or to a test group where aspirin therapy was continued. Outcome measures Bleeding-time test, intra-operative bleeding. Results In 33 out of the 39 patients, intra-operative bleeding was controlled with sutures and local pressure with gauze. The other six patients (see Table 1) had tranexaminc acid added to the local packing to control bleeding. No postoperative bleeding or other complications were reported at 1 week. Conclusion The study suggests that there is no need to stop low-dose aspirin therapy for dental extractions and risk thromboembolic, cerebrovascular or myocardial complications.

Single odontogenic cysts are very well documented in the literature. Of those less common reports concerning multiple jaw cysts, many have been associated with systemic conditions or syndromes such as Gorlin-Goltz or basal cell naevus syndrome, Hunter's syndrome and mucopolysaccharidosis, for example, Maroteaux-Lamy syndrome. A case of multiple odontogenic keratocysts unassociated with any syndrome is reported so as to add to the growing number of such cases in the literature. The possibility of this case being a partial expression of the Gorlin-Goltz syndrome is discussed.