Heat-killed Limosilactobacillus reuteri ATCC PTA 6475 prevents bone loss in ovariectomized mice: A preliminary study.

Osteoporosis is an important health problem that occurs due to an imbalance between bone formation and resorption. Hormonal deficiency post-menopause is a significant risk factor. The probiotic Limosilactobacillus reuteri has been reported to prevent ovariectomy (Ovx)-induced bone loss in mice and reduce bone loss in postmenopausal women. Despite the numerous health benefits of probiotics, as they are live bacteria, the administration is not risk-free for certain groups (e.g., neonates and immunosuppressed patients). We evaluated the effects of L. reuteri (ATCC PTA 6475) and its heat-killed (postbiotic) form on Ovx-induced bone loss. Adult female mice (BALB/c) were randomly divided into four groups: group C-control (sham); group OVX-C-Ovx; group OVX-POS-Ovx + heat-killed probiotic; group OVX-PRO-Ovx + probiotic. L. reuteri or the postbiotic was administered to the groups (1.3x109 CFU/day) by gavage. Bacterial morphology after heat treatment was accessed by scanning electron microscopy (SEM). The treatment started one week after Ovx and lasted 28 days (4 weeks). The animals were euthanized at the end of the treatment period. Bone microarchitecture and ileum Occludin and pro-inflammatory cytokines gene expression were evaluated by computed microtomography and qPCR techniques, respectively. The Ovx groups had lower percentage of bone volume (BV/TV) and number of bone trabeculae as well as greater total porosity compared to the control group. Treatment with live and heat-killed L. reuteri resulted in higher BV/TV and trabecular thickness than the Ovx group. The heat treatment caused some cell surface disruptions, but its structure resembled that of the live probiotic in SEM analysis. There were no statistical differences in Occludin, Il-6 and Tnf-α gene expression. Both viable and heat-killed L. reuteri prevented bone loss on ovariectomized mice, independently of gut Occludin and intestinal Il-6 and Tnf-α gene expression.

Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil.

This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil

Abstract This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

Effects of α and ß-adrenergic signaling on innate immunity and Porphyromonas gingivalis virulence in an invertebrate model.

To investigate the role of adrenergic signalling (AS) in the host immune response and Porphyromonas gingivalis virulence, we compared norepinephrine (NE) and isoproterenol (ISO) responses in Galleria mellonella. P. gingivalis infection was evaluated by survival; humoral immune responses (i.e. melanization and cecropin and gloverin mRNA expression); cellular immune responses (i.e. haemocyte count, nodulation by histology); and P. gingivalis recovery (CFU/mL). P. gingivalis was cultivated in the presence of ISO (PgISO) or NE and injected into the larvae for survival evaluation. Finally, we co-injected ISO and PgISO to evaluate the concomitant effects on the immune response and bacterial virulence. None of the ligands were toxic to the larvae; ISO increased haemocyte number, even after P. gingivalis infection, by mobilizing sessile haemocytes in a ß-adrenergic-specific manner, while NE showed the opposite effect. ISO treatment reduced larval mortality and the number of recovered bacteria, while NE increased mortality and showed no effect on bacterial recovery. ISO and NE had similar effects on melanization and decreased the expression of cecropin. Although co-cultivation with NE and ISO increased the gene expression of bacterial virulence factors in vitro, only the injection of PgISO increased larval death, which was partially reversed by circulating ISO. Therefore, α- and ß-adrenergic signalling had opposite effects after P. gingivalis infection. Ultimately, the catecholamine influence on the immune response overcame the effect of more virulent strains. The effect of AS directly on the pathogen found in vitro did not translate to the in vivo setting.

Outside the limits of bacterial viability: Postbiotics in the management of periodontitis.

Periodontitis is a major cause of tooth loss in adults worldwide and is caused by an unbalanced oral microbiota in a susceptible host, ultimately leading to tissue breakdown and bone loss. Traditionally, the treatment for periodontitis is scaling and root planing; however, some cases require adjuvant therapy, such as antibiotics administration or surgery. Various factors are involved in the pathogenesis and interact in an unpredictable way, increasing the complexity of the disease and making it difficult to manage. In this context, the administration of probiotics aimed at resolving bacterial dysbiosis and the associated dysregulation of the immune system has been employed in clinical trials with encouraging results. However, the use of viable microorganisms is not risk-free, and immunocompromised patients may develop adverse effects. Therefore, the use of inactivated microbial cells, cell fractions, or soluble products and metabolites of probiotics, known as postbiotics, has gained increasing attention. In this commentary, we present the current literature assessing the impact of postbiotics on the growth and metabolism of periodontal pathogens, as well as on the progression of periodontitis in rodents and humans. We also discuss the limitations of the available data and what the scientific community should consider in order to transfer this innovative therapeutic modality from the bench to the bedside.

Estresse e periodontite: avaliação da inervação simpática no periodonto e da resposta adrenérgica após infecção por Porphyromonas gingivalis / Stress and periodontitis: evaluation of sympathetic innervation in the periodontium and the influence of adrenergic signaling on Porphyromonas gingivalis infection

O estresse agrava a doença periodontal por vários mecanismos, sendo a estimulação do sistema nervoso simpático (SNS) um deles. A literatura mostra que a estimulação de receptores ß-adrenérgicos (ß-AR) aumenta a angiogênese em ossos longos, e a expansão microvascular agrava a periodontite. Ainda, catecolaminas aumentam a virulência de periodontopatógenos e agem na resposta imune. Assim, o objetivo deste trabalho foi avaliar: (1) a inervação simpática no periodonto e a influência da ativação do SNS na vascularização periodontal em camundongos e (2) a influência do sistema adrenérgico nos fatores de virulência de Porphyromonas gingivalis (Pg) e na resposta imunológica a este patógeno in vivo (Galleria mellonella). Na primeira parte, camundongos receberam injeção intraperitoneal de solução salina (PBS) ou isoproterenol (ISO; agonista não seletivo ß adrenérgico) por 1 mês, para detecção in situ de tirosina hidroxilase, neuropeptídeo Y, transportador de norepinefrina (NET) e endomucina em mandíbulas. Expressão de mRNA de Vegf-a, Il-1ß, Il-6, Adrb2 e Rankl foi quantificada 2 h após administração de ISO/PBS em mandíbula e tíbias, que serviram como controle positivo. Diferentemente das tíbias, não houve alteração na expressão dos genes analisados em mandíbula. Por outro lado, NET foi mais expresso no osso alveolar do que na tíbia, sendo detectado nos osteoblastos, osteócitos e células do ligamento. Embora o padrão de inervação e a expressão de Adrb2 sejam semelhantes entre mandíbula e tíbia, o tratamento com ISO não influenciou no número e área de vasos positivos para endomucina. Na segunda parte, investigamos a influência adrenérgica na resposta imune de G. mellonella durante infecção por Pg utilizando norepinefrina (NE; agonista α e ß adrenérgico) e ISO. Pg também foi cultivada na presença de ISO (PgISO) ou NE para avaliação da ação direta dos compostos na bactéria. ISO sistêmico protegeu as larvas da infecção por Pg, aumentando o número de hemócitos e reduzindo a contagem de células de Pg na hemolinfa, exclusivamente pelo ß-AR. Diferentemente, NE aumentou mortalidade, diminuiu o número de hemócitos. Apenas PgISO aumentou a morte das larvas, apesar de ambos, NE e ISO, terem aumentado a expressão de fatores de virulência na bactéria in vitro. ISO circulante, concomitante com PgISO, reduziu parcialmente a mortalidade das larvas. A influência do estresse na doença periodontal envolve diversas vias que alteram os dois pilares da periodontite (microbiota e sistema imune). No entanto, a ação na resposta do hospedeiro parece ser superior, uma vez que a estimulação ß-AR em osso alveolar saudável não alterou a produção de citocinas pró-inflamatórias ou microvascularização e a modulação da resposta imune em G. mellonella por compostos adrenérgicos foi mais importante para o desfecho da infecção que sua ação direta sobre a bactéria.

Stress aggravates periodontitis, and one possible mechanism is the activation of sympathetic nervous system (SNS). The literature shows that stimulation of ß-adrenergic receptors (ß-AR) induces angiogenesis in long bones, and microvasculature amplification was linked to periodontitis severity. Moreover, catecholamines increase the virulence of some periodontopathogenic bacteria in vitro and influences the innate immunity. Thus, the aim of this study was (1) evaluate the presence and influence of the SNS in the stimulation of periodontal vasculature, and (2) the influence of the adrenergic system on Porphyromonas gingivalis (Pg) virulence and on the immunological response to this pathogen in vivo (Galleria mellonella larvae). For the first part, mice received isoproterenol (ISO, a non-selective ß-AR agonist) or saline (PBS) for 1 month, for in situ analysis of tyrosine hydroxylase, neuropeptide Y, norepinephrine transporter (NET) and endomucin in the mandibles. Vegfa, Il-1ß, Il-6, Adrb2 and Rankl mRNA expression was assessed 2 hours after PBS/ISO treatment for mandibles and tibia, that served as positive control. We observed that, differently from the tibia, the expression of these genes did not alter on the mandible. However, NET expression was detected in osteoblasts, osteocytes, and periodontal ligament fibroblasts, and were higher expressed when compared to the tibias from the same animals. Although the pattern of sympathetic innervation and Adrb2 expression were similar between tissues, ISO treatment did not increase the area or number of endomucin+ vessels. For the second part, we addressed the adrenergic signaling influence on G. mellonella immune system during Pg infection using norepinephrine (NE, α- and ß-AR agonist), ISO and octopamine (insect's endogenous hormone). Pg was also cultivated in the presence of ISO (PgISO) or NE to investigate the direct action of the ligands on bacterial virulence. Systemic administration of ISO protected the larvae from Pg infection by increasing hemocyte density accompanied by reduction of Pg load in hemolymph, in a ß-AR manner. In contrast, NE increased mortality, with decreased hemocyte count and no influence on the other parameters. Only PgISO increased larvae death, despite of ISO and NE increased virulence in vitro. The concomitant injection of systemic ISO partially reversed the toxicity of the PgISO. The influence of stress on periodontitis involves different pathways, that alter the two pillars of disease's pathogenesis (microbiota and immune system). However, the influence on the host's inflammatory response seems to overcome the other players, since ß-AR activation on healthy alveolar bone didn't alter cytokines production or microvasculature. Besides, the modulation of innate immunity by adrenergic signaling in G. mellonella was more important for the disease's outcome than it's direct action on the bacteria.

Response of the periodontal tissues to ß-adrenergic stimulation.

AIMS: Stimulation of ß-adrenergic receptors (ßAR) in osteoblasts by isoproterenol (ISO) was shown to induce Vascular Endothelial Growth Factor (VEGF) and angiogenesis in long bones. We thus aimed to determine the vascular response of mandibular tissues to ßAR stimulation regarding blood vessel formation. MAIN METHODS: Six-week-old wild-type C57BL6 female mice received daily intraperitoneal injections of ISO or phosphate buffered saline (PBS) for 1 month. Hemimandibles and tibias were collected for immunolocalization of endomucin, tyrosine hydroxylase (TH), neuropeptide Y (NPY) and norepinephrine transporter (NET). Moreover, Vegfa, Il-1 ß, Il-6, Adrb2 and Rankl mRNA expression was assessed in mandibles and tibias 2 h after PBS or ISO treatment. KEY FINDINGS: Despite similar sympathetic innervation and Adrb2 expression between mandibular tissues and tibias, with TH and NPY+ nerve fibers distributed around blood vessels, ISO treatment did not increase endomucin+ vessel area or the total number of endomucin+ vessels in any of the regions investigated (alveolar bone, periodontal ligament, and dental pulp). Consistent with these results, the expression of Vegfα, Il-6, Il-1ß, and Rankl in the mandibular molar region did not change following ISO administration. We detected high expression of NET by immunofluorescence in mandible alveolar osteoblasts, osteocytes, and periodontal ligament fibroblasts, in addition to significantly higher Net expression by qPCR compared to the tibia from the same animals. SIGNIFICANCE: These findings indicate a differential response to ßAR agonists between mandibular and tibial tissues, since the angiogenic potential of sympathetic outflow observed in long bones is absent in periodontal tissues.

Sitagliptin's effects on bone tissue and osseointegration in diabetic rats.

OBJECTIVE: To investigate the effects of sitagliptin, a dipeptidyl peptidase 4 inhibitor used to treat type II diabetes, on bone tissue and on implant osseointegration in diabetic rats. DESIGN: Thirty-two male rats were divided into four groups: 1) Diabetic animals (GD); 2) Diabetic animals that received sitagliptin (GDS); 3) Normoglycemic animals (GN); and 4) Normoglycemic animals that received sitagliptin (GNS). All animals received titanium implants in the right tibia. Sitagliptin or water were administered for 4 weeks. Glycemia, HOMA-IR, insulinemia, microtomographic parameters of the left tibia and implant bone area fraction occupancy (BAFO) of the right tibia were evaluated. RESULTS: The model used to induce diabetes led to hyperglycemia. However, HOMA-IR results showed no insulin resistance, and insulinemia was lower in diabetic animals, demonstrating the development of type I diabetes. Sitagliptin administration did not influence glycemic control. The diabetic animals showed a lower BAFO and bone volume fraction, as well as a lower trabecular number and thickness, revealing the deleterious effect of diabetes on bone metabolism and osseointegration. CONCLUSION: In this model, sitagliptin administration did not reverse the negative effects of type I diabetes on bone, suggesting that sitagliptin has no direct action on bone tissue and has no protective bone action in decompensated diabetic animals.

Oral ulcerative lesions in a post-liver-transplantation patient.

Oral involvement is rarely found in histoplasmosis, except in its disseminated form, which is mostly observed in the severely immunocompromised host. Herein, we presented the case of a 36-year-old female with a previous history of liver transplant, who was hospitalized due to fever, chills, night sweats, diarrhea, and painful oral lesions over the last 3 days. The oral examination revealed the presence of painful shallow ulcers lined by a pseudomembrane in the gingiva and the soft and hard palate. The initial working diagnosis comprised cytomegalovirus reactivation or herpes simplex virus infection. The diagnostic work-up included incisional biopsies of the gingiva and the sigmoid colon. Both biopsies confirmed the diagnosis of histoplasmosis. Intravenous itraconazole was administered with significant improvement after 7 days. Although oral involvement is rare, histoplasmosis should be included in the differential diagnosis of oral lesions, particularly when the patient is immunosuppressed. This study reports a rare presentation of histoplasmosis involving the mucosa of the oral cavity and the colon.

Oral ulcerative lesions in a post-liver-transplantation patient

Oral involvement is rarely found in histoplasmosis, except in its disseminated form, which is mostly observed in the severely immunocompromised host. Herein, we presented the case of a 36-year-old female with a previous history of liver transplant, who was hospitalized due to fever, chills, night sweats, diarrhea, and painful oral lesions over the last 3 days. The oral examination revealed the presence of painful shallow ulcers lined by a pseudomembrane in the gingiva and the soft and hard palate. The initial working diagnosis comprised cytomegalovirus reactivation or herpes simplex virus infection. The diagnostic work-up included incisional biopsies of the gingiva and the sigmoid colon. Both biopsies confirmed the diagnosis of histoplasmosis. Intravenous itraconazole was administered with significant improvement after 7 days. Although oral involvement is rare, histoplasmosis should be included in the differential diagnosis of oral lesions, particularly when the patient is immunosuppressed. This study reports a rare presentation of histoplasmosis involving the mucosa of the oral cavity and the colon.

Agreement, correlation, and kinetics of the alveolar bone-loss measurement methodologies in a ligature-induced periodontitis animal model.

Periodontal research involves the use of animal models to better understand the biological processes of periodontal diseases and the potential of new or existing therapies. Currently, ligature-induced periodontitis in rats is the main model used in periodontal research, in this model, alveolar bone loss (ABL) is the main parameter evaluated by radiographic, morphometric, and histological techniques. Interestingly, although these methodologies are widely used, it is not totally clarified neither the kinetics of ABL over the induction time nor the agreement degree (repeatability and reproducibility) of these techniques. OBJECTIVE: To characterize ABL kinetics at 0, 3, 7, 15, 30, and 60 days after ABL induction by ligature and to evaluate the intra- (repeatability) and inter-examiner (reproducibility) agreement and the correlation among the radiographic, morphometric, and histological methodologies. MATERIAL AND METHODS: 60 male Wistar rats with induced ABL were randomly divided into 6 experimental groups (n = 10 animals/group). After 0, 3, 7, 15, 30, and 60 days, the animals were euthanized and their hemimandibles were removed for ABL determination using radiographic, morphometric and histological techniques. RESULTS: Radiographic and morphometric/linear techniques allowed the detection of statistically significant ABL on the third day, while histological and morphometric/area techniques could only detect ABL after the seventh day (ANOVA/Tukey, p<0.05). After the fifteenth day, except for histological analysis, the ABL was stabilized. Concerning the agreement of the methodologies, Bland Altman's test (intra and inter-examiner evaluations) showed no difference among the measurements (p>0.05). In addition, high correlations (Pearson's test, r2>0.9, p<0.05) were observed. CONCLUSION: The results indicated that the minimum time for ABL induction could vary from 3 to 7 days, according to the chosen analysis methodology. Agreement and correlation data support the comparison of results between studies with same induction time.

Agreement, correlation, and kinetics of the alveolar bone-loss measurement methodologies in a ligature-induced periodontitis animal model

Abstract Periodontal research involves the use of animal models to better understand the biological processes of periodontal diseases and the potential of new or existing therapies. Currently, ligature-induced periodontitis in rats is the main model used in periodontal research, in this model, alveolar bone loss (ABL) is the main parameter evaluated by radiographic, morphometric, and histological techniques. Interestingly, although these methodologies are widely used, it is not totally clarified neither the kinetics of ABL over the induction time nor the agreement degree (repeatability and reproducibility) of these techniques. Objective: To characterize ABL kinetics at 0, 3, 7, 15, 30, and 60 days after ABL induction by ligature and to evaluate the intra- (repeatability) and inter-examiner (reproducibility) agreement and the correlation among the radiographic, morphometric, and histological methodologies. Material and Methods: 60 male Wistar rats with induced ABL were randomly divided into 6 experimental groups (n = 10 animals/group). After 0, 3, 7, 15, 30, and 60 days, the animals were euthanized and their hemimandibles were removed for ABL determination using radiographic, morphometric and histological techniques. Results: Radiographic and morphometric/linear techniques allowed the detection of statistically significant ABL on the third day, while histological and morphometric/area techniques could only detect ABL after the seventh day (ANOVA/Tukey, p<0.05). After the fifteenth day, except for histological analysis, the ABL was stabilized. Concerning the agreement of the methodologies, Bland Altman's test (intra and inter-examiner evaluations) showed no difference among the measurements (p>0.05). In addition, high correlations (Pearson's test, r2>0.9, p<0.05) were observed. Conclusion: The results indicated that the minimum time for ABL induction could vary from 3 to 7 days, according to the chosen analysis methodology. Agreement and correlation data support the comparison of results between studies with same induction time.

Immunomodulatory effect of photodynamic therapy in Galleria mellonella infected with Porphyromonas gingivalis.

Porphyromonas gingivalis is an important pathogen in the development of periodontal disease. Our study investigated if the treatment with antimicrobial photodynamic therapy (aPDT) that employs a nontoxic dye, followed by irradiation with harmless visible light can attenuate the experimental infection of P. gingivalis in Galleria mellonella. Firstly, different concentrations of P. gingivalis ranging from 102 to 106 cells/larva were injected into the animal to obtain a lethal concentration. Next, the following groups of G. mellonella infected with P. gingivalis were evaluated: inoculation of the photosensitizer and application of laser (P + L+), inoculation of physiologic solution and application of laser (P-L+), inoculation the photosensitizer without laser (P + L-) and inoculation of physiologic solution without Laser (P-L-). The effects of aPDT on infection by P. gingivalis were evaluated by survival curve analysis and hemocytes count. A lethal concentration of 106 cells/larva was adopted for evaluating the effects of aPDT on experimental infection with P. gingivalis. We found that after 120 s of PDT application, the death of G. mellonella was significantly lower compared to the control groups (p = 0.0010). Moreover, the hemocyte density in the P+L+ group was increased by 9.6 × 106 cells/mL (2.62-fold increase) compared to the infected larvae with no treatment (L-P- group) (p = 0.0175). Finally, we verified that the aPDT led to a significant reduction of the number of P. gingivalis cells in G. mellonella hemolymph. In conclusion, PDT application was effective against P. gingivalis infection by increasing the survival of G. mellonella and was able to increase the circulating hemocytes indicating that PDT activates the G. mellonella immune system.

Mandible metastasis of small cell lung cancer mimicking a residual cyst.

Small cell lung carcinoma (SCLC) is an uncommon tumor characterized by an aggressive behavior with early metastasis, usually to the contralateral lung, liver, brain, and bones. There are only five cases of this particular tumor metastasizing to the oral cavity described in the English literature. We present the case of metastatic SCLC in the mandible with radiographic findings resembling a residual cyst. A 66-year-old man with previous diagnosis and treatment for a SCLC was referred to the Stomatology Department with a history of persistent pain in the mandible 1 year after the inferior right pre-molar tooth extraction. The radiographic exam showed a well-delimited radiolucent area on that extracted tooth's region resembling a residual cyst. Biopsy was performed yielding the diagnosis of metastatic SCLC. The patient was referred to the clinical oncologist for chemotherapy. Although uncommon, this tumor should be included in the differential diagnosis of jawbone lesions, particularly when the patient presents a previous diagnosis of SCLC.

Mandible metastasis of small cell lung cancer mimicking a residual cyst

Small cell lung carcinoma (SCLC) is an uncommon tumor characterized by an aggressive behavior with early metastasis, usually to the contralateral lung, liver, brain, and bones. There are only five cases of this particular tumor metastasizing to the oral cavity described in the English literature. We present the case of metastatic SCLC in the mandible with radiographic findings resembling a residual cyst. A 66-year-old man with previous diagnosis and treatment for a SCLC was referred to the Stomatology Department with a history of persistent pain in the mandible 1 year after the inferior right pre-molar tooth extraction. The radiographic exam showed a well-delimited radiolucent area on that extracted tooth's region resembling a residual cyst. Biopsy was performed yielding the diagnosis of metastatic SCLC. The patient was referred to the clinical oncologist for chemotherapy. Although uncommon, this tumor should be included in the differential diagnosis of jawbone lesions, particularly when the patient presents a previous diagnosis of SCLC.

Graphite oral tattoo: case report.

Pigmented oral lesions compose a large number of pathological entities, including exogenous pigmentat oral tattoos, such as amalgam and graphite tattoos. We report a rare case of a graphite tattoo on the palate of a 62-year-old patient with a history of pencil injury, compare it with amalgam tattoos, and determine the prevalence of oral tattoos in our Oral Pathology Service. We also compare the clinical and histological findings of grafite and amalgam tattoos. Oral tattoos affect women more frequently in the region of the alveolar ridge. Graphite tattoos occur in younger patients when compared with the amalgam type. Histologically, amalgam lesions represent impregnation of the reticular fibers of vessels and nerves with silver, whereas in cases of graphite tattoos, this impregnation is not observed, but it is common to observe a granulomatous inflammatory response, less evident in cases of amalgam tattoos. Both types of lesions require no treatment, but in some cases a biopsy may be done to rule out melanocytic lesions.

An Isolated Phlebolith on the Lip: An Unusual Case and Review of the Literature.

Background. Calcified thrombi are a common finding, especially in the pelvic veins. There are generally multiple thrombi, and they are generally associated with vascular malformations. Design. Herein we report a rare case of a single labial phlebolith, not associated with any other vascular lesion. We aim to alert clinicians to the possibility of the occurrence of vascular thrombi in the mouth and to describe the clinical and histological characteristics of such lesions in order to simplify the diagnosis and treatment. Furthermore, we have reviewed the English-language literature published since 1970 reporting oral (including masticatory muscles) phleboliths. Results. Twenty-nine cases of phleboliths have been reported in the literature since 1970. Only three of the reported phleboliths were solitary and not associated with other vascular lesions, as in the case presented here. Conclusion. Although phleboliths not associated with other vascular lesions are not common, clinicians should be aware of the existence of this pathology and include it as differential diagnosis of oral lesions.

Efeitos da Exenatida e da Sitagliptina durante a indução da periodontite em ratos / Effects of exenatide and sitagliptin during periodontitis induction in rats

A diabetes mellitus e a periodontite são patologias inflamatórias prevalentes e que se agravam mutuamente. Os novos medicamentos para o tratamento da diabetes, os agonistas do receptor do peptídeo semelhante ao glucagon-1 (GLP-1) e os inibidores da enzima dipeptidil peptidase-4 (DPP-4), têm apresentado efeitos pleiotrópicos como estimulação da formação e inibição da reabsorção óssea e características anti-inflamatórias. O objetivo deste trabalho foi avaliar os efeitos do uso da exenatida (agonista do GLP-1) e da sitagliptina (inibidor da DPP-4) na periodontite induzida em ratos. Foram utilizados 40 ratos divididos em quatro grupos: 1) exenatida (GE):animais com periodontite induzida e que receberam 3 μg/Kg/dia de exenatida por via subcutânea; 2) sitagliptina (GS) animais com periodontite induzida e que receberam 10 mg/Kg/dia de sitagliptina por via oral; 3) com doença periodontal (DP) e 4) controle (GC), ambos receberam os veículos de dissolução dos medicamentos. A periodontite foi induzida pela inserção de ligadura ao redor dos primeiros molares inferiores e os medicamentos foram administrados por 28 dias. No dia do sacrifício, os animais foram pesados e foi coletado sangue para análise sorológica de polipeptídeo insulinotrópico dependente de glicose (GIP), GLP-1, DPP-4 e glicose. As hemimandíbulas foram submetidas à análise radiográfica para avaliação do suporte ósseo alveolar, e a processamento histológico para análise histomorfométrica (área de perda óssea alveolar na região de furca, perda óssea linear interproximal e porcentagem de colágeno). O uso dos medicamentos levou a menor porcentagem de ganho de peso e mas não influenciou a glicemia dos animais. A sitagliptina reduziu a concentração de DPP-4, enquanto a exenatida não aumentou os valores de GLP-1. Nas análises radiográfica e histomorfométrica, comprovou-se a eficácia da indução da periodontite, com diferença significante de suporte ósseo, perda óssea alveolar e porcentagem de colágeno entre os ...

Diabetes Mellitus is a high prevalent disease as well as periodontitis. The literature supports a two way relationship between them. A new class of drugs for diabetes treatment, peptide-like glucagon-1 (GLP-1) agonists and dypeptidyl peptidase-4 (DPP-4) inhibitors, has shown pleiotropic effects, like bone anabolic, antiresoptive and antiinflammatory actions. The aim of this study was to evaluate the effect of exenatide (GLP-1 agonist) and sitagliptin (DPP-4 inhibitor) during periodontitis induction in rats. Forty male rats were divided into four groups:1) exenatide group (GE): animals with induced periodontitis that received 3 μg/Kg/day of exenatide subcutaneously; 2) sitagliptin group (GS): animals with induced periodontitis that received 10 mg/Kg/day with sitagliptin orally; 3) periodontal disease group (PD) and 4) control group (CG); both treated with the drug vehicles. Periodontitis was induced by the insertion of ligature around the first molars and the drugs were administered for 28 days. On the day of sacrifice, animals were weigthed and blood were colleccted for serum analysis of GIP, GLP-1 and DPP-4. The mandibles underwent radiographic analysis for assessment of alveolar bone support, and the histological processing for histomorphometric analysis (area of bone loss in the furcation area, linear interproximal bone loss and percentage of collagen). The use of the drugs led to a lower percentage of weight gain and had no influence on glucose levels. Sitagliptin reduced the concentration of DPP-4, while exenatide had no influence on GLP-1 levels. In radiographic and histomorphometric analysis, it was proved the effectiveness of induction of periodontitis, with a significant difference of bone support, alveolar bone loss and percentage of collagen between the PD and CG. On the other hand there was no statistical difference between the test groups and PD group. In conclusion, within the parameters of this study, both exenatide and sitagliptin were not ...