What is the frequency of floor of the mouth lesions? A descritive study of 4,016 cases.

BACKGROUND: The aim of this study was to investigate the frequency of oral lesions in the floor of the mouth from representative oral pathology centres in Latin America. MATERIAL AND METHODS: This study was conducted on biopsies obtained from January of 1978 to December of 2018 at nine Latin America oral and maxillofacial pathology centres. Gender, age and histopathological diagnosis were evaluated. Data were analysed using descriptive methods. Chi-square test was used for pairwise comparisons. RESULTS: From 114,893 samples, 4,016 lesions (3.49%) occurred in the floor of the mouth. Brazil showed 3,777 cases (94%), Mexico 182 cases (4.5%) and Argentina 57 cases (1.4%). Benign lesions represented 65.1% (2,617 cases), followed by 34.9% (1,404 cases) of malignant disorders. Lesions of epithelial origin were more frequent (1,964 cases; 48.9%), followed by salivary glands (1,245 cases; 31%) and soft tissue lesions (475 cases; 11.7%). The most common histological subtypes were oral squamous cell carcinoma (1,347 cases; 33.5%), ranula (724 cases; 18%), oral leukoplakia (476 cases; 11.8%) and inflammatory fibrous hyperplasia (239 cases; 5.9%). The lesion affected males in 2,129 cases and females in 1,897 cases. CONCLUSIONS: In the current study, lesions in the floor of the mouth represented 3.49% of biopsies submitted to oral pathology services and oral squamous cell carcinoma, ranula and leukoplakia were the most common lesions.

Malignant transformation of oral leukoplakia: a multicentric retrospective study in Brazilian population.

BACKGROUND: Among the oral potentially malignant disorders, leukoplakia stands out as the most prevalent. The purpose of this study was to analyse the clinical-pathological features of oral leukoplakia in groups of patients from three major pathology centers in two different regions of Brazil, in order to determine which factors would be associated to the clinical risk of malignant transformation. MATERIAL AND METHODS: A total of 148 patients was analyzed, and data regarding gender, age, site, classification of the clinical subtype, harmful habits such as use of tobacco and alcohol, time of evolution and presence of dysplasia were collected. The association between risk factors and malignant transformation was investigated using the chi-square test and Fischer's exact test for correlation of variables. A significance level of 5% (p≤0.05) was used. RESULTS: The mean age of the patients was 60 years, and 56% were female. Most of the lesions (34,5%) were located in the lateral and ventral regions of the tongue. Of the 148 patients, ninety had clinical follow-up. Malignant transformation occurred in 13 patients (8.8%), with an average of 44 months of follow up. CONCLUSIONS: Non-smoker, nonhomogeneous clinical presentation, location at the tongue, and the presence of high degree of dysplasia were statistically relevant factors associated with a higher risk of transformation transformation.

Gingival cyst of the adult, lateral periodontal cyst, and botryoid odontogenic cyst: An updated systematic review.

The aim of the present review was to integrate the available data published on gingival cyst of the adult (GCA), lateral periodontal cyst (LPC), and botryoid odontogenic cyst (BOC) into a comprehensive analysis of their clinical/radiological features. An electronic search was undertaken in July/2017. Eligibility criteria included publications having enough clinical/radiological/histological information to confirm the diagnosis. A total of 146 publications (157 GCAs, 213 LPCs, 96 BOCs) were included. GCA and LPC presented highest prevalence in the sixth/fifth decades; BOC in the sixth/seventh decades. LPCs were larger lesions than GCAs and GCAs appeared at an older age than LPC. There was no statistically significant difference between them for other factors (location, symptoms, recurrence, follow-up time). In comparison with LPC, BOC lesions were larger, appeared more often in mandible and in older subjects, had more often a multilocular appearance, and presented a higher recurrence rate. Recurrence rates: GCA (3.2%), LPC (2.4%), BOC (21.7%). No factor seems to influence the recurrence rate of GCA or LPC. Multilocular radiological appearance seems to affect the recurrence rate of BOCs. Conservative surgical approaches seem to be enough for GCA/LPC. BOC presents a more aggressive behavior than GCA/LPC. Therefore, treatment of this lesion might involve some kind of adjunctive therapy after enucleation.

Glandular odontogenic cyst: An updated analysis of 169 cases reported in the literature.

OBJECTIVE: To integrate the available data published on glandular odontogenic cyst (GOC) into a comprehensive analysis of its clinical/radiological and histopathological features. METHODS: An electronic search was undertaken in May/2017. Eligibility criteria included publications having enough clinical/radiological/histological information to confirm the diagnosis. RESULTS: Fifty-eight publications (169 GOCs) were included. The lesion was slightly more prevalent in men than in women. There was a high prevalence in the fifty/sixth decades of life, in the anterior regions, and in mandibles. Lesions were commonly associated with bone expansion (73%) and unilocular radiological appearance (61.5%). GOC was found to be associated with tooth displacement or an unerupted tooth (30.9%), cortical bone perforation (26%), presence of clinical symptoms (24.3%), root resorption (13.9%). Microscopic parameters most commonly were observed in GOCs-in at least 95% of the lesions: presence of hobnail cells, intraepithelial microcysts, epithelial lining with variable thickness. The presence of apocrine snouting was the microscopic parameter less often found (40.4%). CONCLUSION: Although the recurrence rate of GOCs is not as high as previously believed, it is a relevant phenomenon (21.6%). Adjunctive procedures after enucleation should be considered. None of the clinical/radiological and histopathological features evaluated had a statistically significant effect on the recurrence rate.

IL17A polymorphism and elevated IL17A serum levels are associated with oral lichen planus.

OBJECTIVE: The aim of this study was to evaluate the association of IL17A G197A polymorphism and serum levels with oral lichen planus (OLP) susceptibility and clinical presentation. SUBJECTS AND METHODS: Eighty-three individuals diagnosed with OLP and 99 healthy controls (C) were consecutively recruited. All participants had desquamating oral mucosal cells collected and DNA isolated for IL17A (G197A) genotyping. Blood samples of 42 OLP individuals and 23 healthy controls were collected for evaluation of IL17A serum levels. RESULTS: IL17A G197A genotypes were associated with an increased chance of having OLP (GA/AA × GG, OR = 3.44, 95% CI = 1.87-6.33, p < .001). Overall A carriers (GA or AA) were more common in OLP (38.1%) than in C (20.2%; OR = 2.43, 95% CI = 1.53-3.87, p < .001). Serum levels of IL17A were higher among patients with OLP than in healthy controls (reticular, p = .0003; erosive, p < .001), but no difference was found among the disease types. CONCLUSIONS: IL17A G197A is associated with a higher susceptibility of developing OLP and these patients seem to present a considerable increase in IL17A serum levels. These findings suggest that Th17 cells, and IL17A in particular, may play a pivotal role in OLP pathogenesis.

DNA methylation pattern of apoptosis-related genes in ameloblastoma.

OBJECTIVES: DNA methylation is an important mechanism of gene control expression, and it has been poorly addressed in odontogenic tumours. On this basis, we aimed to assess the methylation pattern of 22 apoptosis-related genes in solid ameloblastomas. MATERIALS AND METHODS: Ameloblastoma fresh samples (n = 10) and dental follicles (n = 8) were included in the study. The percentage fraction of methylated and unmethylated DNA promoter of 22 apoptosis-related genes was determined using enzymatic restriction digestion and quantitative real-time PCR (qPCR) array. The relative expressions of the genes that showed the most discrepant methylation profile between tumours and controls were analysed by reverse-transcription quantitative PCR (RT-qPCR). RESULTS: Lower methylation percentages of TNFRSF25 (47.2%) and BCL2L11 (33.2%) were observed in ameloblastomas compared with dental follicles (79.3% and 59.5%, respectively). The RT-qPCR analysis showed increased expression of BCL2L11 in ameloblastomas compared with dental follicles, in agreement with the methylation analysis results, while there was no difference between the expression levels of TNFRSF25 between both groups. CONCLUSIONS: On the basis of our results, the transcription of the apoptosis-related gene BCL2L11 is possibly regulated by promoter DNA methylation in ameloblastoma. The biological significance of this finding in ameloblastoma pathobiology remains to be clarified.

Allelic loss in amalgam-associated oral lichenoid lesions compared to oral lichen planus and mucosa.

BACKGROUND: The amalgam-associated oral lichenoid lesion (AAOLL) shows clinical and histopathological features similar to oral lichen planus (OLP). Molecular researches to improve knowledge of pathogenesis and clinical behavior of AAOLL are still scarce. OBJECTIVE: We investigated for the first time the use of loss of heterozygosity (LOH) as a molecular approach for genetic characterization of AAOLL in comparison with OLP and evaluated the cell proliferation index. MATERIALS AND METHODS: The sample comprised nine AAOLLs, 10 OLPs, and eight NOMs matched by patients' gender and age. LOH was assessed using polymorphic microsatellite markers at chromosomes 9p (D9S157, D9S162, D9S171), 11q (D11S1369), and 17p (TP53, AFM238WF2). Cell proliferation was assessed by immunohistochemical expression of Ki-67 (MIB-1). The association between LOH and Ki-67 was investigated. RESULTS: Loss of heterozygosity occurred in 5/9 AAOLLs and in 2/10 OLPs in at least one marker each, while NOM showed no LOH. Cell proliferation index in AAOLL ranged from 2 to 23%. There was no association between cell proliferation and LOH, independent of the marker. CONCLUSION: Our study shows that the profile of molecular changes in AAOLL and OLP, evaluated by LOH and Ki-67 expression, is similar. Additional studies including larger samples should be performed to confirm or to refute our findings.

A study of the interleukin-1 gene cluster polymorphisms and inflammatory external root resorption in replanted permanent teeth.

AIM: To investigate whether single nucleotide polymorphisms (SNPs) within the interleukin-1 gene cluster (IL1) are associated with the occurrence and severity of inflammatory external root resorption (IERR) after replantation of avulsed permanent teeth. METHODOLOGY: Indexes of IERR were radiographically assessed in 182 mature replanted permanent teeth from 146 patients at the onset of endodontic therapy. DNA was extracted from buccal mucosa cells and genotyped using TaqMan probes-based assays for the SNPs IL1A -889C/T (rs 180058), IL1B +3954C/T (rs1143634) and IL1RN +2018C/T (rs419598). Teeth were grouped into two categories: IERR absent to mild (indexes ≤ 4) and moderate to severe IERR (indexes > 4). Genetic variations in the IL1 gene cluster were tested for their effect on the occurrence and extension of IERR using the GEE model (generalized estimation equation). Patient's age at the moment of injury, timing of pulpectomy, extra-alveolar period and storage condition of the avulsed teeth was included as possible confounders. RESULTS: No association was found between SNPs IL1A -889C/T, IL1B +3954C/T (rs1143634) and IL1RN +2018C/T (rs419598) and IERR indexes. Timing of pulpectomy (OR 3.5 IC 95% 2.0-6.2 P < 0.001) and patient's age at the moment of trauma (OR 0.29 IC 95% 0.12-0.67 P = 0.004) significantly affected the risk of developing severe IERR. CONCLUSIONS: While timing of pulpectomy and patient's age at the moment of trauma were confirmed as important risk factors, SNPs within the IL1 gene cluster did not affect the susceptibility for IERR after replantation of permanent teeth.

Effectiveness of different treatments for odontogenic keratocyst: a network meta-analysis.

Odontogenic keratocysts (OKC) are benign but aggressive lesions. As there is a lack of well randomized clinical studies assessing the effectiveness of the different treatment options for OKC, a network meta-analysis (NMA) was performed to identify the best treatment option with the lowest recurrence rate. An electronic search was performed following the PRISMA guidelines to identify all clinical studies comparing treatment options against enucleation alone. The outcome variable was recurrence. The predictor variables were treatments. The eight included treatments were: enucleation with peripheral ostectomy/curettage (E + PO/curettage); enucleation with cryotherapy (E + CRYO); enucleation with/without PO followed by modified Carnoy's solution (E ± PO+MCS); enucleation with PO and with topical 5-fluorouracil (E + PO+5FU); enucleation with/without PO followed by original Carnoy's solution (E ± PO+CS); marsupialization alone (MARS); marsupialization followed by secondary enucleation with/without PO (MARS+2°E ± PO); and resection. The odds ratio was used to estimate the recurrence rate. A frequentist NMA was performed using Stata software. A total of 2989 patients in 40 studies were included. Both direct pairwise meta-analysis and NMA showed that E + 5FU+PO was significantly superior to E ± PO+MCS. However, no statistically significant difference was found between E ± PO+CS vs E + 5FU+PO, E ± PO+MCS, and resection, respectively (all very low quality evidence). The three most effective treatments in reducing the recurrence rate were E + PO+ 5FU (98.1%; very low quality evidence), resection (83.5%; very low quality evidence), and E ± PO+CS (63.8%; moderate quality evidence). The findings from this study suggest that CS remains the most effective fixative agent after enucleation and PO until proven otherwise. Additionally, 5FU appears to be an effective method with promising results that needs further research. Finally, the efficacy of MCS remains controversial; further in vivo and in vitro studies are required to determine new protocols. As this NMA included retrospective studies, the results should be interpreted with great caution (level of evidence: type III).

Treatments for Burning Mouth Syndrome: A Network Meta-analysis.

The aim of this systematic review and network meta-analysis (NMA) of randomized controlled trials was to evaluate the effectiveness of treatments for pain relief of burning mouth syndrome (BMS). Five databases and gray literature were searched. Independent reviewers selected studies, extracted data, and assessed the risk of bias. The primary outcome was pain relief or burning sensation, and the secondary outcomes were side effects, quality of life, salivary flow, and TNF-α and interleukin 6 levels. Four comparable interventions were grouped into different network geometries to ensure the transitivity assumption for pain: photobiomodulation therapy, alpha-lipoic acid, phytotherapics, and anxiolytics/antidepressants. Mean difference (MD) and 95% CI were calculated for continuous outcomes. The minimal important difference to consider a therapy beneficial against placebo was an MD of at least -1 for relief of pain. To interpret the results, the GRADE approach for NMA was used with a minimally contextualized framework and the magnitude of the effect. Forty-four trials were included (24 in the NMA). The anxiolytic (clonazepam) probably reduces the pain of BMS when compared with placebo (MD, -1.88; 95% CI, -2.61 to -1.16; moderate certainty). Photobiomodulation therapy (MD, -1.90; 95% CI, -3.58 to -0.21) and pregabalin (MD, -2.40; 95% CI, -3.49 to -1.32) achieved the minimal important difference of a beneficial effect with low or very low certainty. Among all tested treatments, only clonazepam is likely to reduce the pain of BMS when compared with placebo. The majority of the other treatments had low and very low certainty, mainly due to imprecision, indirectness, and intransitivity. More randomized controlled trials comparing treatments against placebo are encouraged to confirm the evidence and test possible alternative treatments (PROSPERO CRD42021255039).

Aggregatibacter actinomycetemcomitans serotypes infections and periodontal conditions: a two-way assessment.

This study investigated a large population of individuals positive for A. actinomycetemcomitans and performed a two way analysis assessing the relation between the different serotypes of the bacterium and periodontal conditions. The serotypes analysis (serotypes a, b, c, d, e, f) showed that out of the 204 selected individuals positive for A. actinomycetemcomitans, 152 were positive for a single serotype, 27 showed a variable mixed infection and 25 individuals were not positive for any of the serotypes tested. Serotypes a, b and c were largely found (98%), and serotype c was the most prevalent. Serotypes d, e, and f were either not detected or relatively rare. It was also verified that in non-periodontitis individuals, serotypes a and c were more prevalent (p<0.05); in individuals with mild or moderate/severe chronic periodontitis serotype c was also more common (p<0.05); and aggressive periodontitis subjects showed high prevalence of both serotypes b and c (p<0.05). In conclusion, our study showed that serotype c was the most prevalent in both diseased and healthy subjects. Aggressive periodontitis subjects were not exclusively associated with A. actinomycetemcomitans serotype b. Non-typeable strains were either not detected or were relatively infrequent, and serotypes d and f were not detected in the examined Brazilian population.

Saliva and blood interferon gamma levels and IFNG genotypes in acute graft-versus-host disease.

OBJECTIVE: Graft-versus-host disease is a major complication after allogenic hematopoietic stem cell transplantation. Interferon gamma is an important pro-inflammatory cytokine involved in this disease. Cytokine gene polymorphisms are associated with functional differences in cytokine expression and can alter the clinical course of graft-versus-host disease. This study aimed to investigate the association between IFN-γ levels in saliva, blood, and IFNG polymorphisms, as well as the occurrence of acute graft-versus-host disease in allogenic HSCT. SUBJECTS AND METHODS: Fifty-eight consecutive allogenic hematopoietic stem cell transplantation recipients and their donors were prospectively studied. IFN-g levels in saliva and blood were assessed by ELISA. Samples were collected weekly from 7 days before transplantation (day -7) to 100 days after allogenic HSCT (day +100) or until death. Saliva and/or blood samples were obtained from the recipients and donors to determine IFNG gene polymorphisms. RESULTS: Increased saliva and blood IFN-g levels were observed in patients that had developed aGVHD. In the saliva, the peak levels of IFN-g could be found one week before aGVHD diagnosis, while in the blood, peak levels of IFN-g could be only observed upon diagnosis. A significant association could be identified between the recipients'IFNG genotypes and the IFN-g levels in their blood, at +14 days after HSCT. No association could be observed between IFNG gene polymorphisms and the aGVHD. CONCLUSION: The present study shows that the genetic background of recipients can influence the production of IFN-g. Moreover, as IFN-g levels in the saliva and blood were found to be associated with aGVHD development, this cytokine may be a useful predictor of acute graft-versus-host disease.

Microchimerism in labial salivary glands of hematopoietic stem cell transplanted patients.

OBJECTIVE: Microchimerism has been extensively investigated in autoimmune diseases, which display similarities with graft-vs-host disease. This study was conducted to investigate the presence of microchimerism in minor salivary glands of hematopoietic stem cell transplanted patients, one of the targets of graft-vs-host disease. METHODS: Labial salivary glands biopsy specimens from 11 stem cell transplanted patients were analysed. The samples were grouped in control (five specimens from a female-to-female transplantation) and study group (five glands from male-to-female transplantation). One male transplanted patient was used as a positive control. Fluorescence in situ hybridization with Y-chromosome probe and immunofluorescence with anticytokeratin AE1/AE3 and CD45 were used to identify Y-chromosome positive glandular epithelial cells from allogeneic hematopoietic stem cell transplanted patients. RESULTS: In the study group, all samples were positive to Y-chromosome and cytokeratin AE1/AE3, in agreement with the pattern exhibited by male labial salivary gland. None of the samples from control group were positive to Y-chromosome despite being positive to cytokeratin AE1/AE3. Positivity to CD45 was not relevant. CONCLUSION: Microchimerism in the labial salivary glands of sex-mismatched stem cell transplanted patients is a real phenomenon. Further studies are necessary to elucidate the impact of this phenomenon on the clinical status of stem cell transplanted patients.

Impact of WWOX alterations on p73, ΔNp73, p53, cell proliferation and DNA ploidy in salivary gland neoplasms.

OBJECTIVE: WWOX gene is altered in a variety of neoplasms. Wwox is pro-apoptotic through interaction with p73 and may be involved in chromosomal stability by interaction with p73 and p53. The aims of this study were to characterize WWOX transcription, methylation status and immunoexpression in salivary neoplasms and to determine whether these were associated with p73, p53, cell proliferation and DNA ploidy. MATERIALS AND METHODS: Seven malignant and 21 benign fresh salivary neoplasms were included. WWOX expression was determined by RT-PCR and sequencing of transcripts, quantitative PCR and immunohistochemistry. Methylation-specific PCR was used to assess the methylation of its first exon. For p73, ΔNp73, p53 and ki67 immunohistochemistry and ploidy analysis, 29 malignant samples from archives were included. RESULTS: No consistent pattern of WWOX exon 1 methylation was found, but aberrant and novel transcripts were observed in 17/28 neoplasms; 55% of tumours showed reduced WWOX RNA. WWOX RNA levels were associated with p53 immunopositivity. Immunohistochemical Wwox expression did not correlate with methylation status, p53 or p73 expression or proliferation. p73, proliferation and DNA ploidy were associated with malignant phenotype. CONCLUSION: Aberrant WWOX transcription and decreased expression are frequent in salivary neoplasms and WWOX transcription is associated with p53 staining.

HCMV gB genotype and its association with cytokine levels in hematopoietic stem cell transplantation.

BACKGROUND: Glycoprotein B (gB) has been implicated in determining the pathogenicity and clinical outcomes of human cytomegalovirus (HCMV) disease. OBJECTIVE: The purpose of this study was to assess the prevalence of gB genotypes in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the relationship between it and cytokine levels in saliva and blood samples. The impact of these parameters on patients' survival was also investigated. METHODS: Samples were obtained from 63 patients receiving an allo-HSCT. HCMV gB genotyping was carried out by multiplex nested PCR. The cytokine levels were assessed using ELISA assay. RESULTS: A single or mixed genotype infection was detected in the saliva and blood of 36/63 and 52/63 subjects, respectively. Patients with gB2 in their saliva showed lower IL-10 levels in comparison with patients without gB2. Reduced blood levels of IFN-γ and IL-1ß were also found in recipients with the HCMV gB4 genotype compared with patients without it. Decreased IL-1ß and increased IL-10 blood levels were associated with lower survival. However, HCMV gB genotypes have no impact on patient outcome. CONCLUSION: Decreased IL-1ß and increased IL-10 levels in the blood are associated with lower survival. HCMV genotypes are associated with different cytokine levels in saliva and blood.

Cherubism: a systematic literature review of clinical and molecular aspects.

The purpose of this review was to integrate the clinical, radiological, microscopic, and molecular data of published cherubism cases, in addition to therapeutic approaches, to provide more concise information about the disease. An electronic search was undertaken in September 2019. Eligibility criteria included publications having enough clinical, radiological, and histological information to confirm the diagnosis. A total of 260 publications reporting 513 cherubism cases were included. Familial history was observed in 310/458 cases (67.7%). SH3BP2 mutations were reported in 101/108 cases (93.5%) and mainly occurred at protein residues 415, 418, 419, and 420. Retrospective clinical grading was possible in 175 cases. Advanced clinical grading was associated with tooth agenesis, but not with other clinical, radiological, and genetic features. Specific amino acid substitutions of SH3BP2 mutations were not associated with the clinical grading of the disease. 'Wait and see' was the most common therapeutic approach. In a small number of cases, drugs were used in the treatment, with variable response. In conclusion, there is no clear correlation between the genotype and the phenotype of the disease, but additional genomic and gene expression regulation information is necessary for a better understanding of cherubism.

Saliva as a source of HCMV DNA in allogeneic stem cell transplantation patients.

OBJECTIVE: The purpose of this study was to investigate the use of saliva for the identification of human cytomegalovirus (HCMV) in allogeneic hematopoietic stem cell transplant patients by real time PCR compared with blood. MATERIALS AND METHODS: Saliva and blood samples were sampled weekly in 30 allogeneic hematopoietic stem cell transplant patients until 100 days after transplant. Total genomic DNA, extracted from saliva and whole-blood samples, was used for HCMV real time PCR. Nonparametric tests were performed, and P value

Juvenile ossifying fibroma of the jaws and paranasal sinuses: a systematic review of the cases reported in the literature.

The aim was to compare clinical and radiological features of the two juvenile ossifying fibroma (JOF) variants, trabecular (JTOF) and juvenile psammomatoid ossifying fibroma (JPOF). An electronic search was undertaken in March 2019. Eligibility criteria included publications having sufficient clinical, radiological, and histological information to confirm the diagnosis. A total of 185 publications and 491 cases were included. Most JOFs, including both variants, showed bone expansion, were painless, presented no cortical perforation and no secondary aneurysmal bone cyst, did not cause tooth root resorption, and had a mixed unilocular radiodensity appearance and well-defined limits on radiological examination. Patients with JPOF were on average older than those with JTOF. Enucleation and curettage was associated with a considerably high recurrence rate, regardless of the anatomical location or variant type of the lesion. Enucleation followed by either curettage or peripheral osteotomy showed lower recurrence rates than enucleation only. When resection was performed, only one case of JTOF presented recurrence. In conclusion, JOF lesions presented high rates of recurrence after treatment by curettage and enucleation only. Although surgical resection of JOFs resulted in the virtual absence of recurrence, enucleation followed by peripheral osteotomy/curettage should be the treatment of choice for both JOF variants to avoid the disfigurement usually associated with surgical resection.

Nicotinic receptor-evoked hippocampal norepinephrine release is highly sensitive to inhibition by isoflurane.

BACKGROUND: Inhaled anaesthetics (IAs) produce multiple dose-dependent behavioural effects including amnesia, hypnosis, and immobility in response to painful stimuli that are mediated by distinct anatomical, cellular, and molecular mechanisms. Amnesia is produced at lower anaesthetic concentrations compared with hypnosis or immobility. Nicotinic acetylcholine receptors (nAChRs) modulate hippocampal neural network correlates of memory and are highly sensitive to IAs. Activation of hippocampal nAChRs stimulates the release of norepinephrine (NE), a neurotransmitter implicated in modulating hippocampal synaptic plasticity. We tested the hypothesis that IAs disrupt hippocampal synaptic mechanisms critical to memory by determining the effects of isoflurane on NE release from hippocampal nerve terminals. METHODS: Isolated nerve terminals prepared from adult male Sprague-Dawley rat hippocampus were radiolabelled with [(3)H]NE and either [(14)C]GABA or [(14)C]glutamate and superfused at 37 degrees C. Release evoked by a 2 min pulse of 100 microM nicotine or 5 microM 4-aminopyridine was evaluated in the presence or absence of isoflurane and/or selective antagonists. RESULTS: Nicotine-evoked NE release from rat hippocampal nerve terminals was nAChR- and Ca(2+)-dependent, involved both alpha7 and non-alpha7 subunit-containing nAChRs, and was partially dependent on voltage-gated Na(+) channel activation based on sensitivities to various antagonists. Isoflurane inhibited nicotine-evoked NE release (IC(50)=0.18 mM) more potently than depolarization-evoked NE release (IC(50)=0.27 mM, P=0.014), consistent with distinct presynaptic mechanisms of IA action. CONCLUSIONS: Inhibition of hippocampal nAChR-dependent NE release by subanaesthetic concentrations of isoflurane supports a role in IA-induced amnesia.

Novel mutations in the SH3BP2 gene associated with sporadic central giant cell lesions and cherubism.

Central giant cell lesion (CGCL) is a reactive bone lesion that occurs mainly in the mandible, characterized by the multinucleated osteoclast-like giant cells in a background of oval to spindle-shaped mononuclear cells. The etiology is unknown and occurs more commonly in young adults. Cherubism, a rare disease found predominantly in females has histologic characteristics indistinguishable from those of CGCL and is caused by mutations mostly present in exon 9 of the SH3BP2 gene. In this study, we investigated four cases of CGCL and one case of cherubism. DNA was extracted from peripheral blood and tumor tissue and all coding and flanking regions of the SH3BP2 amplified by PCR and directly sequenced to identify underlying mutations. Two novel mutations were found; a heterozygous missense mutation c.1442A>T (Q481L) in exon 11 in one sporadic case of CGCL and a heterozygous germline and tumor tissue missense mutation c.320C>T (T107M) in exon 4 in one patient with cherubism. These findings open a new window to investigate the possible relationship between the pathogenesis of the cherubism and CGCL.