Search

Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. There are some studies in the literature demonstrating association between cytokines genes polymorphisms and susceptibility to develop some immune-mediate conditions. The purpose of this study was to investigate cytokine gene polymorphisms in a sample of Brazilian patients with OLP. Fifty-three patients with OLP (mean age = 43.1 years; range 20-68 years) and 53 healthy volunteers (mean age = 42.9 years; range 21-67) were genotyped for IL-1beta +3954 (C/T), IL-6-174 (G/C), IL-10-1082 (G/A) and TNFA-308 (G/A) gene polymorphisms. Statistical analysis was based on the use of logistic regression (P-values below 0.05 were considered as significant). IL-6 and TNFA homozygous genotypes were significantly more often detected in OLP patients. These genotypes were associated with an increased risk of OLP development (OR 6.89 and 13.04, respectively). IL-1beta and IL-10 gene polymorphisms were not related to OLP development. Our findings clearly demonstrate an association between inheritance of IL-6 and TNFA gene polymorphisms and OLP occurrence, thus giving additional support for genetic basis of this disease. [ABSTRACT FROM AUTHOR]

The present study evaluates the effect of including microencapsulated hot chili pepper (MHCP) in the diet of crossbred dairy cows on the volume and quality of milk and on ovarian morphofunctionality. Twenty-four crossbred females in their lactating period were used. The cows were divided into two experimental groups, a control (CT) and an MHCP -supplemented group (CP) given 1 g a day per animal of microencapsulated hot chili in concentrate for 42 days. Over seven weeks of daily milk production was measured, and sample milk was collected weekly for composition analysis. Animals were subject to an ovulation synchronization protocol on day 0 (D0), and an intravaginal progesterone (P4) implant, estradiol benzoate, and prostaglandin (PGF2α) were administered. On D8, the P4 implant was removed and PGF2α, equine chorionic gonadotropin, and estradiol cypionate were administered to the animals. The ovarian dynamics were evaluated in B mode and color Doppler. There were significant differences ( p < 0.05) in the group X time interaction, the volume of milk produced, and the amount in kg/day of milk components. There was a higher percentage of vascularization in the preovulatory follicle in the CP group ( p ≥ 0.10). The findings show that the inclusion of MHCP in the diet of dairy cows does influence their milk production and reproduction.

Estimating the parturition date in dogs is challenging due to their reproductive peculiarities that. Ultrasonographic examination serves as a tool for studying embryo/foetal biometry and estimating the time of parturition by measuring foetal and extra-foetal structures. However, due to reproductive differences among various dog breeds, such estimates may have a non-significant pattern, representing inaccuracies in the estimated date of birth. This study aimed to monitor pregnant Toy Poodle bitches and establish relationships between ultrasonographically measured foetal and extra-foetal dimensions and the remaining time until parturition. Eighteen pregnant Toy Poodle bitches were subjected to weekly ultrasonographic evaluations and measurements of the inner chorionic cavity diameter, craniocaudal length (CCL), biparietal diameter (BPD), diameter of the deep portion of diencephalo-telencephalic vesicle (DPTV), abdominal diameter, thorax diameter (TXD), placental thickness and the renal diameter (REND). These parameters were retrospectively correlated with the date of parturition and linear regressions were established between gestational measurements and days before parturition (DBP). All analyses were conducted using the Statistical Package for Social Sciences (IBM® SPSS®) program at a 5% significance level. The foetal measurements that showed a high correlation (r) and reliability (R 2 ) with DBP were BPD [(DBP = [15.538 × BPD] - 39.756), r = .97 and R 2  = .93], TXD [(DBP = [8.933 × TXD] - 32.487), r = .94 and R 2  = .89], DPTV [(DBP = [34.580 × DPTV] - 39.403), r = .93 and R 2  = .86] and REND [(DBP = [13.735 × REND] - 28.937), r = .91 and R 2  = .82]. This statistically validates the application of these specific formulas to estimate the parturition date in Toy Poodle bitches., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Hypoglycemia is the most common metabolic alteration in the clinical routine of newborn dogs, acting as a predictor of mortality in these patients. The neonatal dog shows hepatic insufficiency and homeostatic mechanisms not yet fully developed, with limited glycogen reserves and limited capacity to perform glycogenolysis and gluconeogenesis. These physiological particularities make newborn dogs particularly susceptible to hypoglycemia when of fasting, even for short periods. Several maternal and neonatal factors may be related to a higher risk of developing hypoglycemia in neonates. This paper reviews glycemic homeostasis, the pathophysiology of neonatal hypoglycemia, the main causes involved and the diagnostic and therapeutic approaches to this condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fuchs, Pereira, Xavier, Mendonça, Barreto, Silva, de Souza and Lourenço.)

Since the 1970s, maternal corticosteroid therapy has been used successfully to induce labor. This allows for better monitoring of parturients and provision of first aid to neonates, improving neonatal viability, as this treatment induces maturation in a variety of fetal tissues, thereby reducing morbidity and mortality. Although the effects of corticosteroids are well known, few studies have investigated the influence of this therapy in Santa Inês sheep. This study aimed to evaluate the efficacy of dexamethasone at two doses (8 and 16 mg) to induce lambing in Santa Inês ewes at 145 days of gestation and assess its effects on neonatal vitality. For this study, 58 ewes raised in an extensive system were investigated. Pregnancy was confirmed after artificial insemination at a set time or after controlled mounting. Ewes were separated into three groups: an untreated control group (G1: 0 mg) and groups treated with two doses of dexamethasone (G2: 8 mg and G3: 16 mg). In total, 79 lambs were born. Their vitality was assessed based on their Apgar score, weight, temperature, and postnatal behavior. SAS v9.1.3 (SAS Institute, Cary, NC) was used to analyze data, considering a 5% significance level for all analyses. The births in the induced groups occurred 48.4 ± 22.1 h after induction, while the ewes that underwent non-induced labor gave birth 131.96 ± 41.9 h after placebo application (p < 0.05), confirming the efficacy of dexamethasone to induce and synchronize labor. The induced and non-induced neonates had similar Apgar scores, temperatures, weights, and postnatal behavioral parameters (p > 0.05). This study showed that inducing labor in Santa Inês ewes at 145 days of gestation with a full (16 mg) or half dose (8 mg) of dexamethasone is an effective technique and does not compromise neonate vitality., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare.

Individuals can experience accentuated disputes for resources when living with many conspecifics, even in situations in which cooperative behaviors assure benefits associated with an increase in the frequency of food acquisition and in diet breadth. Thus, intraspecific competition may exert a significant selective pressure on social animals. Theoretical models suggest that females of social species could improve their fitness by producing relatively large offspring, since body size can provide competitive advantages during foraging activities. As female reserves are limited, the production of large offspring would occur at the expense of their number. Using five Anelosimus (Araneae, Theridiidae) species, we assessed whether the social ones produce fewer and larger eggs than the subsocials. In addition, we tested the effect of female size on the adoption of each particular reproductive strategy. Small females could hypothetically invest in producing large offspring since they cannot produce as many offspring as large females. Our results suggested that, indeed, sociality influences reproductive strategies. Females of social species produced fewer and larger offspring than females of subsocial species. Subsociality, in turn, would benefit the production of many small spiderlings, possibly because a large number of siblings is important to maintain and expand new webs and to subdue prey during their initial instars. Our results also indicated that large females produce more eggs without necessarily reduce their sizes. We discussed how the costs and benefits of group living may influence reproductive strategies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Birth and the first few weeks of age are critical periods of developing the immune system of puppies and kittens and adapting to an environment containing a variety of infectious agents. The survival rate during these periods depends mainly on the newborn's immune capacity to prevent and combat infections. Although most components of innate and adaptive immunity are present at birth, responses are slow and immature compared to adults. Due to immunological immaturity and the endotheliochorial placental structure, circulating concentrations of immunoglobulins in dogs and cats at birth are quite low. Thus, newborns need a prompt and immediate immune response, which is essentially provided by defense cells and maternal antibodies via colostrum. Failure to ingest colostrum is correlated with high mortality rates in the neonatal period. Concurrently, factors related to pregnant, such as pregnancy physiological immunosuppression and nutritional and health states, can directly influence newborn immunity and health. Therefore, understanding the maternal and neonatal immunological aspects, importance of colostrum, risk factors for failure to transfer passive immunity and colostrum substitute strategies are essential to ensure the survival of the litter., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

There is a high perinatal mortality rate in dogs, estimated at 20%, and one of the leading causes of this rate is hypoglycaemia. Therefore, we aimed to evaluate the efficacy of a hypercaloric supplement containing vitamins and amino acids in newborn puppies presenting hypoglycaemia at birth. Ninety-nine pups were divided into four groups: normoglycaemic caesarean section (NORMOCS), hypoglycaemic caesarean section supplemented with the hypercaloric (SUPLCS), hypoglycaemic caesarean section supplemented with glucose (GLICCS) and eutocic delivery (EUT). We evaluated the following parameters glycaemia, Apgar score, neurological reflexes and rectal temperature of neonates at the following moments 5 min (M5), 30 min (M30) and 60 min (M60) after birth. Brachycephalic dogs were 73.3% (22/30) of caesarean sections (c-sections). The puppy's average glycaemia represented about 90% of the maternal glycaemia, while 15.1% (14/99) of the neonates had hypoglycaemia (<90 mg/dL) at M0 and 46.5% (44/99) at M60. Only four neonates had glycaemia below 40 mg/dL at M30 but without showing any clinical signs. The puppy's fasting while waiting for the intraoperative period and the dam's anaesthetic recovery was considered risk factors for hypoglycaemia. There was no difference in mean blood glucose levels or vitality parameters among puppies from the SUPLCS and GLICCS. In conclusion, the hypercaloric supplement can be used as a replacement for glucose in hypoglycaemic puppies and it can also bring nutritional benefits for the puppy. The prepartum glycaemia of the dam is an important parameter to be measured, and the appropriate management of it reduces the chances of the puppies being born with hypoglycaemia., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

The mammalian dentition is a serially homogeneous structure that exhibits wide numerical and morphological variation among multiple different species. Patterning of the dentition is achieved through complex reiterative molecular signaling interactions that occur throughout the process of odontogenesis. The secreted signaling molecule Sonic hedgehog (Shh) plays a key role in this process, and the Shh coreceptor growth arrest-specific 1 (Gas1) is expressed in odontogenic mesenchyme and epithelium during multiple stages of tooth development. We show that mice engineered with Gas1 loss-of-function mutation have variation in number, morphology, and size of teeth within their molar dentition. Specifically, supernumerary teeth with variable morphology are present mesial to the first molar with high penetrance, while molar teeth are characterized by the presence of both additional and absent cusps, combined with reduced dimensions and exacerbated by the presence of a supernumerary tooth. We demonstrate that the supernumerary tooth in Gas1 mutant mice arises through proliferation and survival of vestigial tooth germs and that Gas1 function in cranial neural crest cells is essential for the regulation of tooth number, acting to restrict Wnt and downstream FGF signaling in odontogenic epithelium through facilitation of Shh signal transduction. Moreover, regulation of tooth number is independent of the additional Hedgehog coreceptors Cdon and Boc, which are also expressed in multiple regions of the developing tooth germ. Interestingly, further reduction of Hedgehog pathway activity in Shh tm6Amc hypomorphic mice leads to fusion of the molar field and reduced prevalence of supernumerary teeth in a Gas1 mutant background. Finally, we demonstrate defective coronal morphology and reduced coronal dimensions in the molar dentition of human subjects identified with pathogenic mutations in GAS1 and SHH/GAS1 , suggesting that regulation of Hedgehog signaling through GAS1 is also essential for normal patterning of the human dentition.

Orb-webs show diversity in several traits, including silk types, architecture, physical properties, locale, and period of exposition. The investigation of how they determine the identity of intercepted prey is important to functional ecology and to the evaluation of trophic niche partitioning within communities. However, the influence of several of these variables on the composition of intercepted insects remains to be determined. In this study, we evaluated the effects of web architectural traits, height, and daily periods of exposition on the interception of different insects in terms of sizes, masses, and taxa. We conducted observations of prey intercepted by the orb webs of 16 sympatric spider species and artificial webs. We found that all orb webs mainly intercepted small and light insects, sharing the most abundant insect families found in the study area. However, spiders that show nocturnal activity, more radii in their webs, large and high webs captured heavier insects. Other orb-web traits, such as the density of capture threads did not influence the kind of intercepted insects. We discuss why some variables affected prey interceptions in terms of mass. Finally, we discuss the implications of these influential variables to functional ecology, niche differentiation, and how behavioral assessments can complete this investigation in future studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Oral cancer is a significant health problem worldwide. Oral squamous cell carcinoma (OSCC) is a malignant neoplasm of epithelial cells that mostly affects different anatomical sites in the head and neck and derives from the squamous epithelium or displays similar morphological characteristics. Generally, OSCC is often the end stage of several changes in the stratified squamous epithelium, which begin as epithelial dysplasia and progress by breaking the basement membrane and invading adjacent tissues. Several plant-based drugs with potent anti-cancer effects are considered inexpensive treatments with limited side effects for cancer and other diseases., Objective: The aim of this review is to explore whether some Brazilian plant extracts or constituents exhibit anti-tumorigenic activity or have a cytotoxic effect on human oral carcinoma cells., Methods: Briefly, OSCC and several metabolites derived from Brazilian plants (i.e., flavonoids, vinblastine, irinotecan, etoposide and paclitaxel) were used as keywords to search the literature on PubMed, GenBank and GeneCards., Results: The results showed that these five chemical compounds found in Cerrado Biome plants exhibit anti-neoplastic effects. Evaluating the compounds revealed that they play a main role in the regulation of cell proliferation., Conclusion: Preserving and utilising the biodiversity of our planet, especially in unique ecosystems, such as the Cerrado Biome, may prove essential to preserving and promoting human health in modern contexts., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Before using estimators, it is essential to consider their efficiency in order to avoid bias in results. Due to the architectural and structural complexity of spider webs, some important variables involved in prey capture are usually estimated based on a few measurements obtained from photographs. One of these variables is the capture thread length (CTL), which can provide valuable information on foraging behaviours and the energetic investment in prey capture. However, many of the webs found in the field are damaged, and there is no automatic method to measure the CTL. Therefore, the determination of a simple and accurate estimator of this variable is important to several studies involving spider foraging strategies. In this study, we assessed the accuracy of traditional and new CTL estimators and their vulnerability to web shape and asymmetry. Our results validated the accuracy of the previous estimators. However, we also presented a simple new estimator that can be even more accurate, irrespective of whether the webs exhibit circular shapes or asymmetry in thread investment between superior and inferior web parts. Moreover, we presented an accurate CTL estimator for non-circular orb webs, for which the traditional ones are not applicable., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The tongue is a highly specialised muscular organ with a complex anatomy required for normal function. We have utilised multiple genetic approaches to investigate local temporospatial requirements for sonic hedgehog (SHH) signalling during tongue development. Mice lacking a Shh cis -enhancer, MFCS4 ( ShhMFCS4/- ), with reduced SHH in dorsal tongue epithelium have perturbed lingual septum tendon formation and disrupted intrinsic muscle patterning, with these defects reproduced following global Shh deletion from E10.5 in pCag - CreERTM; Shhflox/flox embryos. SHH responsiveness was diminished in local cranial neural crest cell (CNCC) populations in both mutants, with SHH targeting these cells through the primary cilium. CNCC-specific deletion of orofaciodigital syndrome 1 ( Ofd1 ), which encodes a ciliary protein, in Wnt1-Cre; Ofdfl/Y mice led to a complete loss of normal myotube arrangement and hypoglossia. In contrast, mesoderm-specific deletion of Ofd1 in Mesp1-Cre; Ofdfl/Y embryos resulted in normal intrinsic muscle arrangement. Collectively, these findings suggest key temporospatial requirements for local SHH signalling in tongue development (specifically, lingual tendon differentiation and intrinsic muscle patterning through signalling to CNCCs) and provide further mechanistic insight into the tongue anomalies seen in patients with disrupted hedgehog signalling., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

The vertebrate tongue is a complex muscular organ situated in the oral cavity and involved in multiple functions including mastication, taste sensation, articulation and the maintenance of oral health. Although the gross embryological contributions to tongue formation have been known for many years, it is only relatively recently that the molecular pathways regulating these processes have begun to be discovered. In particular, there is now evidence that the Hedgehog, TGF-Beta, Wnt and Notch signaling pathways all play an important role in mediating appropriate signaling interactions between the epithelial, cranial neural crest and mesodermal cell populations that are required to form the tongue. In humans, a number of congenital abnormalities that affect gross morphology of the tongue have also been described, occurring in isolation or as part of a developmental syndrome, which can greatly impact on the health and well-being of affected individuals. These anomalies can range from an absence of tongue formation (aglossia) through to diminutive (microglossia), enlarged (macroglossia) or bifid tongue. Here, we present an overview of the gross anatomy and embryology of mammalian tongue development, focusing on the molecular processes underlying formation of the musculature and connective tissues within this organ. We also survey the clinical presentation of tongue anomalies seen in human populations, whilst considering their developmental and genetic etiology., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

The aim of this systematic review was to assess qualitative changes induced by fixed appliance orthodontic treatment on the subgingival microbiota. Seven databases were searched up to August 2017 for randomized and nonrandomized clinical studies assessing the effect of orthodontic appliances on the subgingival bacteria in human patients. After elimination of duplicate studies, data extraction and risk of bias assessment according to the Cochrane guidelines, random-effects meta-analyses of relative risks (RR) and their 95% confidence intervals (CIs) were performed. According to controlled studies, the presence of Aggregatibacter actinomycetemcomitans in the subgingival crevicular fluid of orthodontic patients was increased 3-6 months after fixed appliance insertion compared to untreated patients (2 studies; RR = 15.54; 95% CI = 3.19-75.85). There was still increased subgingival prevalence of Aggregatibacter actinomycetemcomitans (3 studies; RR = 3.98; 95% CI = 1.23-12.89) and Tannerella forsythia in orthodontic patients up to 6 months after appliance removal compared to untreated patients. However, caution is warranted due to high risk of bias and imprecision. Insertion of orthodontic fixed appliances seems to be associated with a qualitative change of subgingival microbiota, which reverts to some extent back to normal in the first months after appliance removal. However, there is limited evidence on the timing and extent of these changes., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Clinical trial registration is widely recommended because it allows tracking of trials that helps ensure full and unbiased reporting of their results. The aim of the present overview was to provide empirical evidence on bias associated with trial registration via a meta-epidemiological approach., Study Design and Settings: Six databases were searched in September 2017 for randomized clinical trials and systematic reviews thereof assessing the effects of orthodontic clinical interventions. After duplicate study selection and data extraction, statistical analysis included a two-step meta-epidemiological approach within- and across-included meta-analyses with a Paule-Mandel random-effects model to calculate differences in standardized mean differences (ΔSMD) between registered and unregistered trials and their 95% confidence intervals (CI), followed by subgroup and sensitivity analyses., Results: A total of 16 meta-analyses with 83 trials and 4,988 patients collectively were finally included, which indicated that registered trials reported less beneficial treatment effects than unregistered trials (ΔSMD = -0.36; 95% CI = -0.60, -0.12). Although some small-study effects were identified, sensitivity analyses according to precision and risk of bias indicated robustness., Conclusion: Signs of bias from lack of trial protocol registration were found with nonregistered trials reporting more beneficial intervention effects than registered ones. Caution is warranted by the interpretation of nonregistered randomized trials or systematic reviews thereof., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Microdeletion of chromosome 22q11 is associated with significant developmental anomalies, including disruption of the cardiac outflow tract, thymic/parathyroid aplasia and cleft palate. Amongst the genes within this region, TBX1 is a major candidate for many of these developmental defects. Targeted deletion of Tbx1 in the mouse has provided significant insight into the function of this transcription factor during early development of the cardiac and pharyngeal systems. However, less is known about its role during palatogenesis. To assess the influence of Tbx1 function on gene expression profile within the developing palate we performed a microarray screen using total RNA isolated from the secondary palate of E13.5 mouse embryos wild type, heterozygous and mutant for Tbx1., Results: Expression-level filtering and statistical analysis revealed a total of 577 genes differentially expressed across genotypes. Data were clustered into 3 groups based on comparison between genotypes. Group A was composed of differentially expressed genes in mutant compared to wild type (n = 89); Group B included differentially expressed genes in heterozygous compared to wild type (n = 400) and Group C included differentially expressed genes in mutant compared to heterozygous (n = 88). High-throughput quantitative real-time PCR (RT-PCR) confirmed a total of 27 genes significantly changed between wild type and mutant; and 27 genes between heterozygote and mutant. Amongst these, the majority were present in both groups A and C (26 genes). Associations existed with hypertrophic cardiomyopathy, cardiac muscle contraction, dilated cardiomyopathy, focal adhesion, tight junction and calcium signalling pathways. No significant differences in gene expression were found between wild type and heterozygous palatal shelves., Conclusions: Significant differences in gene expression profile within the secondary palate of wild type and mutant embryos is consistent with a primary role for Tbx1 during palatogenesis.

Cleft lip with or without palate (CLP) and isolated cleft palate (CP) are common human developmental malformations with a complex etiology that reflects a failure of normal facial development. VAX1 encodes a homeobox-containing transcription factor identified as a candidate gene for CLP in human populations, with targeted deletion in mice associated with multiple anomalies, including disruption of the visual apparatus and basal forebrain, lobar holoprosencephaly, and CP. We have investigated Vax1 function during murine palatogenesis but found no evidence for a direct role in this process. Vax1 is not expressed in the developing palate and mutant palatal shelves elevate above the tongue, demonstrating morphology and proliferation indices indistinguishable from wild type. However, mutant mice did have a large midline cavity originating from the embryonic forebrain situated beneath the floor of the hypothalamus and extending through the nasal cavity to expand this region and prevent approximation of the palatal shelves. Interestingly, despite strong expression of Vax1 in ectoderm of the medial nasal processes, the upper lip remained intact in mutant mice. We found further evidence of disrupted craniofacial morphology in Vax1 mutants, including truncation of the midface associated with reduced cell proliferation in forebrain neuroectoderm and frontonasal mesenchyme. Sonic hedgehog (Shh) signal transduction was downregulated in the mutant forebrain, consistent with a role for Vax1 in mediating transduction of this pathway. However, Shh was also reduced in this region, suggestive of a Shh-Vax1 feedback loop during early development of the forebrain and a likely mechanism for the underlying lobar holoprosencephaly. Despite significant associations between VAX1 and human forms of CLP, we find no evidence of a direct role for this transcription factor in development of this region in a mutant mouse model.

The first step towards the prevention of cancer is to develop an in-depth understanding of tumourigenesis and the molecular basis of malignant transformation. What drives tumour initiation? Why do most benign tumours fail to metastasize? Oncogenic mutations, previously considered to be the hallmark drivers of cancers, are reported in benign cysts and tumours, including those that have an odontogenic origin. Despite the presence of such alterations, the vast majority of odontogenic lesions are benign and never progress to the stage of malignant transformation. As these lesions are likely to develop due to developmental defects, it is possible that they harbour quiet genomes. Now the question arises - do they result from DNA replication errors? Specific candidate genes have been sequenced in odontogenic lesions, revealing recurrent BRAF mutation in the case of ameloblastoma, KRAS mutation in adenomatoid odontogenic tumours, PTCH1 mutation in odontogenic keratocysts, and CTNNB1 (Beta-catenin) mutation in calcifying odontogenic cysts. Studies on these benign and rare entities might reveal important information about the tumorigenic process and the mechanisms that hinder/halt neoplastic progression. This is because the role of relatively common oncogenic mutations seems to be context dependent. In this review, each mutation signature of the odontogenic lesion and the affected signalling pathways are discussed in the context of tooth development and tumorigenesis. Furthermore, behavioural differences between different types of odontogenic lesions are explored and discussed based on the molecular alteration described. This review also includes the employment of molecular results for guiding therapeutic approaches towards odontogenic lesions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Sonic hedgehog (Shh) is an essential signaling peptide required for normal embryonic development. It represents a highly-conserved marker of odontogenesis amongst the toothed vertebrates. Signal transduction is involved in early specification of the tooth-forming epithelium in the oral cavity, and, ultimately, in defining tooth number within the established dentition. Shh also promotes the morphogenetic movement of epithelial cells in the early tooth bud, and influences cell cycle regulation, morphogenesis, and differentiation in the tooth germ. More recently, Shh has been identified as a stem cell regulator in the continuously erupting incisors of mice. Here, we review contemporary data relating to the role of Shh in odontogenesis, focusing on tooth development in mammals and cartilaginous fishes. We also describe the multiple actions of this signaling protein at the cellular level., Competing Interests: The authors declare no conflict of interest.

Abnormal regulation of Sonic hedgehog (Shh) signaling has been described in a variety of human cancers and developmental anomalies, which highlights the essential role of this signaling molecule in cell cycle regulation and embryonic development. Gas1 and Boc are membrane co-receptors for Shh, which demonstrate overlapping domains of expression in the early face. This study aims to investigate potential interactions between these co-receptors during formation of the secondary palate. Mice with targeted mutation in Gas1 and Boc were used to generate Gas1; Boc compound mutants. The expression of key Hedgehog signaling family members was examined in detail during palatogenesis via radioactive in situ hybridization. Morphometric analysis involved computational quantification of BrdU-labeling and cell packing; whilst TUNEL staining was used to assay cell death. Ablation of Boc in a Gas1 mutant background leads to reduced Shh activity in the palatal shelves and an increase in the penetrance and severity of cleft palate, associated with failed elevation, increased proliferation and reduced cell death. Our findings suggest a dual requirement for Boc and Gas1 during early development of the palate, mediating cell cycle regulation during growth and subsequent fusion of the palatal shelves.

The Hedgehog signalling pathway plays a fundamental role in orchestrating normal craniofacial development in vertebrates. In particular, Sonic hedgehog (Shh) is produced in three key domains during the early formation of the head; neuroectoderm of the ventral forebrain, facial ectoderm and the pharyngeal endoderm; with signal transduction evident in both ectodermal and mesenchymal tissue compartments. Shh signalling from the prechordal plate and ventral midline of the diencephalon is required for appropriate division of the eyefield and forebrain, with mutation in a number of pathway components associated with Holoprosencephaly, a clinically heterogeneous developmental defect characterized by a failure of the early forebrain vesicle to divide into distinct halves. In addition, signalling from the pharyngeal endoderm and facial ectoderm plays an essential role during development of the face, influencing cranial neural crest cells that migrate into the early facial processes. In recent years, the complexity of Shh signalling has been highlighted by the identification of multiple novel proteins that are involved in regulating both the release and reception of this protein. Here, we review the contributions of Shh signalling during early craniofacial development, focusing on Hedgehog receptor function and describing the consequences of disruption for inherited anomalies of this region in both mouse models and human populations., (Copyright © 2016. Published by Elsevier Inc.)

The Eph family receptor-interacting (ephrin) ligands and erythropoietin-producing hepatocellular carcinoma (Eph) receptors constitute the largest known family of receptor tyrosine kinases. Ephrin ligands and their receptors form an important cell communication system with widespread roles in normal physiology and disease pathogenesis. In order to investigate potential roles of the ephrin-Eph system during palatogenesis and tongue development, we have characterized the cellular mRNA expression of family members EphrinA1-A3, EphA1-A8, and EphrinB2, EphB1, EphB4 during murine embryogenesis between embryonic day 13.5-16.5 using radioactive in situ hybridization. With the exception of EphA6 and ephrinA3, all genes were regionally expressed during the process of palatogenesis, with restricted and often overlapping domains. Transcripts were identified in the palate epithelium, localized at the tip of the palatal shelves, in the mesenchyme and also confined to the medial epithelium seam. Numerous Eph transcripts were also identified during tongue development. In particular, EphA1 and EphA2 demonstrated a highly restricted and specific expression in the tongue epithelium at all stages examined, whereas EphA3 was strongly expressed in the lateral tongue mesenchyme. These results suggest regulatory roles for ephrin-EphA signaling in development of the murine palate and tongue.

Objectives: Meta-analysis is the gold standard for synthesizing evidence on the effectiveness of health care interventions. However, its validity is dependent on the quality of included studies. Here, we investigated whether basic study design (i.e., randomization and timing of data collection) in orthodontic research influences the results of clinical trials., Study Design and Setting: This meta-epidemiologic study used unrestricted electronic and manual searching for meta-analyses in orthodontics. Differences in standardized mean differences (ΔSMD) between interventions and their 95% confidence intervals (CIs) were calculated according to study design through random-effects meta-regression. Effects were then pooled with random-effects meta-analyses., Results: No difference was found between randomized and nonrandomized trials (25 meta-analyses; ΔSMD = 0.07; 95% CI = -0.21, 0.34; P = 0.630). However, retrospective nonrandomized trials reported inflated treatment effects compared with prospective (40 meta-analyses; ΔSMD = -0.30; 95% CI = -0.53, -0.06; P = 0.018). No difference was found between randomized trials with adequate and those with unclear/inadequate generation (25 meta-analyses; ΔSMD = 0.01; 95% CI = -0.25, 0.26; P = 0.957). Finally, subgroup analyses indicated that the results of randomized and nonrandomized trials differed significantly according to scope of the trial (effectiveness or adverse effects; P = 0.005)., Conclusion: Caution is warranted when interpreting systematic reviews investigating clinical orthodontic interventions when nonrandomized and especially retrospective nonrandomized studies are included in the meta-analysis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In common with most mammals, humans form only two dentitions during their lifetime. Occasionally, supernumerary teeth develop in addition to the normal complement. Odontoma represent a small group of malformations containing calcified dental tissues of both epithelial and mesenchymal origin, with varying levels of organization, including tooth-like structures. The specific cell type responsible for the induction of odontoma, which retains the capacity to re-initiate de novo tooth development in postnatal tissues, is not known. Here we demonstrate that aberrant activation of WNT signaling by expression of a non-degradable form of β-catenin specifically in SOX2-positive postnatal dental epithelial stem cells is sufficient to generate odontoma containing multiple tooth-like structures complete with all dental tissue layers. Genetic lineage-tracing confirms that odontoma form in a similar manner to normal teeth, derived from both the mutation-sustaining epithelial stem cells and adjacent mesenchymal tissues. Activation of the WNT pathway in embryonic SOX2-positive progenitors results in ectopic expression of secreted signals that promote odontogenesis throughout the oral cavity. Significantly, the inductive potential of epithelial dental stem cells is retained in postnatal tissues, and up-regulation of WNT signaling specifically in these cells is sufficient to promote generation and growth of ectopic malformations faithfully resembling human odontoma.

Human dental development is characterized by formation of primary teeth, which are subsequently replaced by the secondary dentition. The secondary dentition consists of incisors, canines, and premolars, which are derived from the successional dental lamina of the corresponding primary tooth germs; and molar teeth, which develop as a continuation of the dental lamina. Currently, very little is known about the molecular regulation of human successional tooth formation. Here, we have investigated expression of three candidate regulators for human successional tooth formation; the Fibroblast Growth Factor-antagonist SPROUTY2, the Hedgehog co-receptor GAS1 and the RUNT-related transcription factor RUNX2. At around 8 weeks of development, only SPROUTY2 showed strong expression in both epithelium and mesenchyme of the early bud. During the cap stage between 12-14 weeks, SPROUTY2 predominated in the dental papilla and inner enamel epithelium of the developing tooth. No specific expression was seen in the successional dental lamina. GAS1 was expressed in dental papilla and follicle, and associated with mesenchyme adjacent to the primary dental lamina during the late cap stage. In addition, GAS1 was identifiable in mesenchyme adjacent to the successional lamina, particularly in the developing primary first molar. For RUNX2, expression predominated in the dental papilla and follicle. Localized expression was seen in mesenchyme adjacent to the primary dental lamina at the late cap stage; but surprisingly, not in the early successional lamina at these stages. These findings confirm that SPROUTY2, GAS1, and RUNX2 are all expressed during early human tooth development. The domains of GAS1 and RUNX2 are consistent with a role influencing function of the primary dental lamina but only GAS1 transcripts were identifiable in the successional lamina at these early stages of development.

Holoprosencephaly is a heterogeneous developmental malformation of the central nervous system characterized by impaired forebrain cleavage, midline facial anomalies and wide phenotypic variation. Indeed, microforms represent the mildest manifestation, associated with facial anomalies but an intact central nervous system. In many cases, perturbations in sonic hedgehog signaling are responsible for holoprosencephaly. Here, we have elucidated the contribution of Gas1 and an additional hedgehog co-receptor, Boc during early development of the craniofacial midline, by generating single and compound mutant mice. Significantly, we find Boc has an essential role in the etiology of a unique form of lobar holoprosencephaly that only occurs in conjunction with combined loss of Gas1. Whilst Gas1(-/-) mice have microform holoprosencephaly characterized by a single median maxillary central incisor, cleft palate and pituitary anomalies, Boc(-/-) mice have a normal facial midline. However, Gas1(-/-); Boc(-/-) mutants have lobar holoprosencephaly associated with clefting of the lip, palate and tongue, secondary to reduced sonic hedgehog transduction in the central nervous system and face. Moreover, maxillary incisor development is severely disrupted in these mice, arresting prior to cellular differentiation as a result of apoptosis in the odontogenic epithelium. Thus, Boc and Gas1 retain an essential function in these tooth germs, independent of their role in midline development of the central nervous system and face. Collectively, this phenotype demonstrates both redundancy and individual requirements for Gas1 and Boc during sonic hedgehog transduction in the craniofacial midline and suggests BOC as a potential digenic locus for lobar holoprosencephaly in human populations., (© 2014. Published by The Company of Biologists Ltd.)

The vertebrate Scube family consists of three independent members Scube1-3; which encode secreted cell surface-associated membrane glycoproteins that share a domain organization of at least five recognizable motifs and the ability to both homo- and heterodimerize. There is recent biochemical evidence to suggest that Scube2 is directly involved in Hedgehog signaling, acting co-operatively with Dispatched to mediate the release in soluble form of cholesterol and palmitate-modified Hedgehog ligand during long-range activity. Indeed, in the zebrafish myotome, all three Scube proteins can subtly promote Hedgehog signal transduction in a non-cell autonomous manner. In order to further investigate the role of Scube genes during development, we have generated mice with targeted inactivation of Scube3. Despite a dynamic developmental expression pattern, with transcripts present in neuroectoderm, endoderm and endochondral tissues, particularly within the craniofacial region; an absence of Scube3 function results in no overt embryonic phenotype in the mouse. Mutant mice are born at expected Mendelian ratios, are both viable and fertile, and seemingly retain normal Hedgehog signaling activity in craniofacial tissues. These findings suggest that in the mouse, Scube3 is dispensable for normal development; however, they do not exclude the possibility of a co-operative role for Scube3 with other Scube members during embryogenesis or a potential role in adult tissue homeostasis over the long-term.

Background: Oculocutaneous albinism (OCA) is an autosomal recessive hereditary pigmentation disorder affecting humans and several other animal species. Oculocutaneous albinism was studied in a herd of Murrah buffalo to determine the clinical presentation and genetic basis of albinism in this species., Results: Clinical examinations and pedigree analysis were performed in an affected herd, and wild-type and OCA tyrosinase mRNA sequences were obtained. The main clinical findings were photophobia and a lack of pigmentation of the hair, skin, horns, hooves, mucosa, and iris. The results of segregation analysis suggest that this disease is acquired through recessive inheritance. In the OCA buffalo, a single-base substitution was detected at nucleotide 1,431 (G to A), which leads to the conversion of tryptophan into a stop codon at residue 477., Conclusion: This premature stop codon produces an inactive protein, which is responsible for the OCA buffalo phenotype. These findings will be useful for future studies of albinism in buffalo and as a possible model to study diseases caused by a premature stop codon.

The Scube (Signal peptide CUB EGF-like domain-containing protein) family consists of three independent members evolutionarily conserved from zebrafish to humans. Scube2 transcripts have been identified primarily in forebrain and trunk neuroepithelium and the anterior hindbrain of the mouse embryo, becoming progressively localized to the dorsal forebrain, hindbrain and neural tube. Zebrafish You-class mutants lack a functional C-terminal domain within the Scube2 protein and present with altered myotomal morphology, curled tail and weak cyclopia. These defects are characteristic of disrupted Hedgehog signaling, which is consistent with the downregulation of Hedgehog targets such as Ptc1, MyoD and Eng observed in these mutants. Indeed, human SCUBE2 can form a complex with Sonic hedgehog and its receptor PTC1, acting to promote SHH-induced signaling. Here we have characterized Scube2 expression in detail within the developing mouse embryo using wholemount and section in situ hybridisation and demonstrate the presence of transcripts within a more extensive range than previously reported. In addition to neuroectoderm of the early embryo, expression was also found in the developing face, heart, vasculature and multiple regions of the endochondral skeleton. These findings suggest that Scube2 may play an important role during development of multiple regions in the embryo.

TNF-α may be associated with the etiopathogenesis of oral lichen planus (OLP), and it has been suggested that polymorphism of mannose-binding lectin (MBL) increases the in vitro production of TNF- α. The aim of the present study was to assess the relevance of genetic diversity of MBL in OLP. The study sample comprised 90 individuals, 45 OLP patients and 45 healthy volunteers. MBL-2 gene was amplified using real-time PCR. Frequency of A/A genotype was 55.6% in OLP and 53.3% in healthy volunteers. Likewise, A/0 heterozygote genotype was found in 42.2% and 35.6%; 2.2% and 11.1%, had the recessive 0/0 genotype respectively. Frequencies of the "A" and "0" alleles were 77% and 23% in the OLP group and 71.2% in control group. There were no statistically significant differences regarding genotype frequency (p = 0.546) or allele frequency (p = 0.497). In conclusion, no significant association was found between polymorphism of MBL-2 gene and OLP.

The SCUBE gene family encode secreted, extracellular proteins that share a distinct domain organization of at least five recognizable motifs, including an amino-terminal signal peptide sequence, multiple EGF-like domains, a large spacer region containing multiple N-linked glycosylation sites, three repeated stretches of six-cysteine residues and a carboxy-terminal CUB domain. We describe a Scube3(tm1Dge/H) targeted allele, which replaces the entire coding region for Exons 2 and 3 with a neomycin-lacZ selectable marker cassette predicted to delete the first two EGF-like domains of the transcribed protein. Scube3(+/tm1Dge/H) embryos demonstrate strong β-galactosidase activity in the early facial epithelium, including the branchial arches and facial processes, the otic vesicle, limb buds, and neural tube. In addition, strong reporter activity was identified in the epithelial compartments of developing teeth and hair follicles. However, analysis of the Scube3(tm1Dge/H) allele revealed that it encodes a truncated protein, which contains part of the spacer region and CUB domain. It is likely that this protein retains functionality because our analysis reveals that Scube3(tm1Dge/H; tm1Dge/H) mice are phenotypically normal. Whilst acting as a useful reporter, these mice do not provide any insight into the potential role of Scube3 during embryonic development., (Copyright © 2010 Wiley-Liss, Inc.)

The neighbor of Brca1 gene (Nbr1) functions as an autophagy receptor involved in targeting ubiquitinated proteins for degradation. It also has a dual role as a scaffold protein to regulate growth-factor receptor and downstream signaling pathways. We show that genetic truncation of murine Nbr1 leads to an age-dependent increase in bone mass and bone mineral density through increased osteoblast differentiation and activity. At 6 mo of age, despite normal body size, homozygous mutant animals (Nbr1(tr/tr)) have approximately 50% more bone than littermate controls. Truncated Nbr1 (trNbr1) co-localizes with p62, a structurally similar interacting scaffold protein, and the autophagosome marker LC3 in osteoblasts, but unlike the full-length protein, trNbr1 fails to complex with activated p38 MAPK. Nbr1(tr/tr) osteoblasts and osteoclasts show increased activation of p38 MAPK, and significantly, pharmacological inhibition of the p38 MAPK pathway in vitro abrogates the increased osteoblast differentiation of Nbr1(tr/tr) cells. Nbr1 truncation also leads to increased p62 protein expression. We show a role for Nbr1 in bone remodeling, where loss of function leads to perturbation of p62 levels and hyperactivation of p38 MAPK that favors osteoblastogenesis.

Supernumerary teeth are a common clinical and radiographic finding and may produce occlusal and dental problems. The aetiological basis of extra teeth is poorly understood in human populations; however, the mouse provides a useful model system to investigate the complex genetics of tooth development. This article describes recent advances in our understanding of the genetic basis of supernumerary teeth. We have reviewed biological evidence that provides insight into why supernumerary tooth formation may occur. Indeed, many of the molecular signalling pathways known to be involved in normal development of the tooth germ can also give rise to additional teeth if inappropriately regulated. These include components of the Hedgehog, FGF, Wnt, TNF and BMP families, which provide a useful resource of candidate genes that may potentially play a role in human supernumerary tooth formation.

Scube1 encodes a secreted plasma membrane-associated protein characterized by a N-terminal signal peptide sequence, multiple EGF domains, a N-linked glycosylated spacer region and a C-terminal CUB region. Here, we describe expression of the mouse Scube1 gene during early craniofacial development. Transcripts were identified in the nervous system, within the ventral neural tube, telencephalon and trigeminal ganglion. In addition, strong regionally restricted expression was found in the facial processes, including the medial and lateral nasal processes, maxilla and mandible, and caudal pharyngeal arches. During tooth development, Scube1 localized to the dental papilla of both incisor and molar teeth. Together, these data suggest a potential role for Scube1 during early craniofacial development., ((c) 2008 Wiley-Liss, Inc.)

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant or spontaneous disorder characterized by multiple cutaneous basal cell carcinomas, odontogenic keratocysts, skeletal anomalies and facial dysmorphology, including cleft lip and palate. Causative mutations for NBCCS occur in the PTCH1 gene on chromosome 9q22.3-q31, which encodes the principle receptor for the Hedgehog signalling pathway. We have investigated the molecular basis of craniofacial defects seen in NBCCS using a transgenic mouse model expressing Shh in basal epithelium under a Keratin-14 promoter. These mice have an absence of flat bones within the skull vault, hypertelorism, open-bite malocclusion, cleft palate and arrested tooth development. Significantly, increased Hedgehog signal transduction in these mice can influence cell fate within the craniofacial region. In medial edge epithelium of the palate, Shh activity prevents apoptosis and subsequent palatal shelf fusion. In contrast, high levels of Shh in odontogenic epithelium arrests tooth development at the bud stage, secondary to a lack of cell proliferation in this region. These findings illustrate the importance of appropriately regulated Hedgehog signalling during early craniofacial development and demonstrate that oro-facial clefting and hypodontia seen in NBCCS can occur as a direct consequence of increased Shh signal activity within embryonic epithelial tissues.

Background: Treatment of latent tuberculosis (TB) infection (LTBI) in Brazil is recommended only in the case of contacts of pulmonary smear-positive TB patients agedor=10 mm and no previous bacille Calmette-Guérin (BCG) vaccination or with a TST>or=15 mm regardless of previous BCG vaccination., Objective: To evaluate the 2-year incidence and predictors of TB among contacts who did not meet the Brazilian criteria for LTBI treatment., Design: Retrospective cohort study. Contacts aged between 12 and 15 years and those aged>or=15 years who did not meet the Brazilian criteria for LTBI treatment were enrolled in the study., Results: TB incidence was 3.2% (22/667), with an estimated TB rate of 1649 per 100000 population. Risk of TB was greater among the 349 contacts with TST>or=5 mm (5.4%) compared to the 318 contacts with TST<5 mm (0.9%; RR 6.04, 95%CI 1.7-20.6)., Conclusion: The high incidence of TB among contacts who did not meet the Brazilian criteria for LTBI treatment strongly suggests that these criteria should be reviewed. Furthermore, even among BCG-vaccinated contacts, TST induration>or=5 mm was the only variable that predicted the development of TB disease within 2years.

Objective: To determine the demographic profile of all histologically diagnosed odontogenic cysts (OC) and nonodontogenic cysts (nOC) over a 51-year period in the Brazilian population., Study Design: Case records of patients with OC and nOC from the files of the Oral Pathology Service, School of Dentistry, Federal University of Minas Gerais, Belo Horizonte, Brazil, during the period of 1953-2003 were evaluated., Results: Among 19,064 oral biopsies, 2,905 (15.2%) presented criteria of OC and nOC. Of these, 2,812 specimens (14.7%) were diagnosed as OC and 93 (0.5%) represented nOC. The 3 most frequent OC diagnosed were radicular cyst (61.0%), dentigerous cyst (25.3%), and odontogenic keratocyst (7.2%). The most frequent nOC was the nasopalatine duct cyst (2.2%)., Conclusion: Our results demonstrate that there is a wide range of OC and nOC, with some cysts having a predilection for age, gender, and localization. We also showed demographic aspects and clinical characteristics of these cysts. These could be used as baseline data to obtain more epidemiologic information about the OC and the nOC especially in the Brazilian population.

Background: Benign migratory glossitis (BMG) is a very common immunological oral disease of unknown aetiology., Methods and Subjects: Fifty-three consecutive subjects affected by BMG and 53 age- and sex-matched control subjects were genotyped for IL-1B, IL-6 and TNFA polymorphisms. Binary logistic regression models were fitted and values of P < 0.05 were considered significant., Results: A significant difference in the distribution of IL-1B genotypes was observed in the group with BMG in univariate analyses (P = 0.01). The multivariate analyses showed that the CT genotype of the IL1-B gene was significantly associated with a high risk to develop BMG (P = 0.02, OR 2.76). The combined presence of IL-1beta high and intermediate producers genotypes was also associated with BMG in multivariate analyses (P = 0.01, OR 3.05). IL-6 and TNFA polymorphisms were not associated with BMG in the univariate and multivariate analyses., Conclusion: Our findings demonstrate that the polymorphism +3954 IL-1B is associated with an increased risk of BMG development and suggest a genetic basis for disease development.

Background: Considerable evidence indicates that serotonergic mechanisms, particularly the serotonin transporter (5-HTT) may be involved in psychiatric alterations. Recent findings have demonstrated that depression and stress are influenced by polymorphism of the promoter region of 5-HTT (5-HTTLPR) and that the short allele (S) is associated with reduced transcriptional efficiency resulting in reduced serotonin expression and uptake. As psychiatric and genetic factors have been implicated in the pathogenesis of oral lichen planus (OLP), the purpose of the present study was to investigate 5-HTTLPR polymorphism in patients with OLP compared to control subjects., Subjects and Methods: Fifty-four subjects affected by OLP and 54 healthy volunteers were genotyped at 5-HTTLPR. The chi-squared test was used for statistical analysis. To investigate the association between the single nucleotide polymorphisms and risk of OLP, binary logistic regression models were fitted., Results: No statistical difference was observed between the genotype and allele frequency in the group of OLP and controls (p=0.51). Moreover no association between 5HTTLPR alleles and OLP was found in the multivariate analyses., Conclusion: Our study demonstrates that polymorphism on the 5-HTTLPR is not associated with OLP pathogenesis.

Aim: To investigate in individuals with symptomatic dental abscesses the occurrence of functional polymorphisms within five genes involved with the immune response. The functional gene polymorphisms analysed were CD14 (-260 C/T), IL1B (+3954 C/T), IL6 (-174 G/C,), IL10 (-1082 G/A) and TNFA (-308 G/A)., Methodology: Genomic DNA obtained from oral swabs from individuals with symptomatic dental abscesses and asymptomatic inflammatory periapical lesions, without previous exacerbation, was submitted to restriction fragment length polymorphism (RFLP) analyses to determine each individual genotype. The chi-square and principal components analysis tests were used for statistical analysis., Results: A significant association was observed between the occurrence of the GG genotype or the G allele expression of the polymorphic locus-174 (G/C) of the IL6 gene, and the presence of the symptomatic dental abscesses in women and in individuals < or =35 years old. The principal components analysis suggested predominance of the symptomatic dental abscesses in individuals displaying: high-producer IL6 genotype; intermediate and high-producer IL1B genotypes and low-producer TNFA genotype., Conclusions: The present study suggests that genetic factors are associated with susceptibility to develop symptomatic dental abscesses.

Background: Interleukin-1 beta (IL-1 beta) is a potent inflammatory mediator and an important polymorphism in the locus +3954 (C/T) of the human IL1 B gene has been shown to affect the levels of this cytokine. This functional polymorphism has been associated with the establishment of inflammatory diseases, including periodontal disease, in European, Asian and North American populations., Objective: The aim of this study was to investigate the association between the IL1 B (+3954) gene polymorphism and the occurrence of different clinical forms of periodontitis in a sample of Brazilian individuals., Methods: This study employed a cross-sectional design involving individuals from the State of Minas Gerais in the south-eastern region of Brazil. Genomic DNA was obtained from oral swabs of 129 individuals and amplified using the polymerase chain reaction (PCR) with specific primers flanking the locus +3954 of IL1 B. PCR products were submitted to restriction endonuclease digestion and analyzed by polyacrylamide gel electrophoresis, to distinguish alleles T and C of the IL1 B gene, allowing for the determination of the genotypes and detection of the polymorphism., Results and Conclusions: The chronic periodontitis group displayed a higher percentage of the T allele (28%) when compared to the aggressive periodontitis group (10.7%, chi(2)=5.24, p=0.02, OR=0.31, CI=0.11--0.88) and to control group (8.7%, chi(2)=7.11, p=0.007, OR=0.24, CI=0.08--0.73). Our data suggested that the polymorphism in the locus +3954 of IL1 B gene could be a risk factor for chronic periodontitis in a sample of Brazilian individuals.

Background: Central giant cell lesion (CGCL) is a reactive lesion of the jaws with an associated inflammatory infiltrate. Since cell circulation allows for intense communication between different compartments in the body, we investigated whether the CGCL would lead to phenotypic and/or functional changes in circulating leukocytes., Methods: We obtained lymphocytes and monocytes from CGCL patients and control subjects, to evaluate cytokine and adhesion molecule expression using flow cytometry., Results: Our results revealed that CD4(+) T cells and CD14(+) monocytes from CGCL express elevated levels of CD11a and CD11b, respectively, when compared with controls. The frequencies of CD4(+) T cells expressing interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha and the frequencies of CD4(+) and CD14(+) cells expressing interleukin (IL)-10 were increased in CGCL group, when compared with controls., Conclusions: Our data indicate that, although CGCL is a localized lesion, the patients show systemic functional alterations in circulating leukocytes, suggesting their role in the inflammatory pathogenesis of CGCL.