A case of larva migrans representing a pitfall in oral diagnosis.

The present work reports a case of a female patient complaining of itching and painful lesions affecting the oral mucosa for 7 months. Buccal and lip mucosa showed swelling and erythema, with serpiginous tracks. The patient was diagnosed with oral larva migrans, and the lesions resolved after ivermectin administration. At 18-month follow-up, no sign of recurrence was observed. Larva migrans can represent a pitfall in oral diagnosis and a stressful condition for the patient. Oral health care providers should be aware of this and keep this disease in mind as a possible differential diagnosis in oral mucosa lesions.

Oral cancer over six decades: a multivariable analysis of a clinicopathologic retrospective study.

Studies have reported changes in the epidemiological profile of patients with oral cancer in recent decades, especially regarding gender and age. This study aimed to evaluate a historical series of oral malignant lesions prevalence over six decades and define characteristics associated with the occurrence, mainly, of oral squamous cell carcinoma (OSCC). A retrospective review of histopathological records from 1953 to 2019 was conducted in three oral pathology laboratories in South Brazil about age, sex, anatomical site, clinical aspect, and histopathological diagnosis. Descriptive and analytical analyses were performed comparing the histopathological diagnoses with other variables. Multivariable logistic regression was applied to determine the associated predictors of OSCC. Of the 53,065 records available in the institutions, 986 were oral malignant tumors (including all malignant neoplasms), representing 1.86% of all diagnoses. The occurrence of OSCC in the 1960's was 80.0%, decreasing over time reaching the lowest percentage of cases in the 1990's (75.8%) and significantly increasing to 88.7% in the 2010s. Females had a lower chance than males of having OSCC independently of the decade (odds ratio=0.30, p<0.001). This was the same for older individuals compared to those younger than 40 years. No interactions between sex, age, and decade were observed. The number of diagnoses of oral malignant lesions increased over time, and the occurrence of OSCC varied. Older individuals and males had higher chances of having OSCC independently of the decade. Therefore, in this study sample, no changes were observed in the epidemiological profile over the years concerning these predictors.

Oral cancer over six decades: a multivariable analysis of a clinicopathologic retrospective study

Abstract Studies have reported changes in the epidemiological profile of patients with oral cancer in recent decades, especially regarding gender and age. This study aimed to evaluate a historical series of oral malignant lesions prevalence over six decades and define characteristics associated with the occurrence, mainly, of oral squamous cell carcinoma (OSCC). A retrospective review of histopathological records from 1953 to 2019 was conducted in three oral pathology laboratories in South Brazil about age, sex, anatomical site, clinical aspect, and histopathological diagnosis. Descriptive and analytical analyses were performed comparing the histopathological diagnoses with other variables. Multivariable logistic regression was applied to determine the associated predictors of OSCC. Of the 53,065 records available in the institutions, 986 were oral malignant tumors (including all malignant neoplasms), representing 1.86% of all diagnoses. The occurrence of OSCC in the 1960's was 80.0%, decreasing over time reaching the lowest percentage of cases in the 1990's (75.8%) and significantly increasing to 88.7% in the 2010s. Females had a lower chance than males of having OSCC independently of the decade (odds ratio=0.30, p<0.001). This was the same for older individuals compared to those younger than 40 years. No interactions between sex, age, and decade were observed. The number of diagnoses of oral malignant lesions increased over time, and the occurrence of OSCC varied. Older individuals and males had higher chances of having OSCC independently of the decade. Therefore, in this study sample, no changes were observed in the epidemiological profile over the years concerning these predictors.

Resumo Alguns estudos relataram mudanças no perfil epidemiológico dos pacientes com câncer bucal nas últimas décadas, principalmente quanto ao gênero e a idade. Este estudo teve como objetivo avaliar, em uma série histórica, a prevalência de todas as lesões malignas bucais ao longo de seis décadas e definir características associadas na ocorrência, principalmente, de carcinoma espinocelular (CEC). Um levantamento retrospectivo dos registros histopatológicos de 1953 a 2019 foi realizado em três laboratórios de Patologia Bucal no Sul do Brasil em relação à idade, gênero, sítio anatômico, aspecto clínico e diagnóstico histopatológico. Análises descritivas e analíticas foram realizadas comparando-se os diagnósticos histopatológicos com as outras variáveis. A regressão logística multivariada foi aplicada para determinar os possíveis preditores associados ao CEC. Dos 53.065 prontuários disponíveis nas instituições, 986 eram tumores malignos bucais (incluindo todas as neoplasias malignas), representando 1,86% de todos os diagnósticos. A ocorrência de CEC na década de 1960 foi de 80,0%, diminuindo ao longo do tempo, atingindo o menor percentual de casos na década de 1990 (75,8%) e aumentando significativamente para 88,7% na década de 2010. As mulheres tiveram menor risco de desenvolver CEC do que os homens, independentemente da década (OR=0,30, p<0,001). Este foi o mesmo para indivíduos com idade mais avançada em comparação com aqueles com menos de 40 anos de idade. Não foram observadas interações entre gênero, idade e década. O número de diagnósticos de lesões malignas bucais aumentou ao longo das décadas e a ocorrência de CEC variou. Indivíduos com mais de 40 anos e do sexo masculino tiveram maiores chances de ter CEC, independentemente da década analisada. Portanto, nessa amostra estudada, não foram observadas mudanças no perfil epidemiológico ao longo dos anos com relação a esses preditores.

Adverse effects of deoxycholic acid in submandibular glands, submental, inguinal and subplantar regions: a study in rats.

OBJECTIVE: We aimed to evaluate the effects of the deoxycholic acid (DCA) in the submental and subplantar regions of rats, and to histologically analyze the changes caused in the submandibular glands, soft tissues of the paw, and inguinal adipose tissue. MATERIAL AND METHODS: Sixty male Wistar rats were divided into DCA and control (CG) groups. DCA was injected in the submental, inguinal, and subplantar regions, and saline was injected in the CG. The animals were euthanized after 24 h and at 7 and 21 days. RESULTS: The DCA group showed edema in the submental region in 24 h and in the paw in all experimental times. In the paw there were also erythema and ulceration in 7 days, and alopecia after 21 days. At 21 days, a few animals also showed erythema and ulceration in paw; however, there was no significant difference from CG. Histological analysis of the paw showed an intense inflammatory process, with a predominance of neutrophils, lymphocytes, and plasma cells in 24 h and 7 days. In the adipose tissue, we observed loss of architecture and inflammatory infiltrate, followed with a lower number of adipose cells, and at 21 days, fibroplasia. In the submandibular glands we observed inflammatory infiltration, loss of tissue architecture, and fibrosis. CONCLUSIONS: DCA produces a significant inflammatory process in the structures. It can cause skin ulcerations and, in salivary glands, it causes loss of tissue architecture and fibrosis. CLINICAL RELEVANCE: There has been growing increase in the use of DCA for aesthetic purposes by health care providers. Due to the presence of important anatomical structures in the submental region, constant vigilance is required to report new adverse effects.

RvD1 treatment during primary infection modulates memory response increasing viral load during respiratory viral reinfection.

Resolvin D1 (RvD1), which is biosynthesized from essential long-chain fatty acids, is involved in anti-inflammatory activity and modulation of T cell response. Memory CD8+ T cells are important for controlling tumor growth and viral infections. Exacerbated inflammation has been described as impairing memory CD8+ T cell differentiation. This study aimed to verify the effects of RvD1 on memory CD8+ T cells in vitro and in vivo in a respiratory virus infection model. Peripheral blood mononuclear cells were treated at different time points with RvD1 and stimulated with anti-CD3/anti-CD28 antibodies. Pre-treatment with RvD1 increases the expansion of memory CD8+ T cells. The IL-12 level, a cytokine described to control memory CD8+ T cells, was reduced with RvD1 pre-treatment. When the mTOR axis was inhibited, the IL-12 levels were restored. In a respiratory virus infection model, Balb/c mice were treated with RvD1 before infection or after 7 days after infection. RvD1 treatment after infection increased the frequency of memory CD8+ T cells in the lung expressing II4, II10, and Ifng. During reinfection, RvD1-treated and RSV-infected mice present a high viral load in the lung and lower antibody response in the serum. Our results show that RvD1 modulates the expansion and phenotype of memory CD8+ T cells but contributed to a non-protective response after RSV reinfection.

Impact of endodontic and periodontal diseases and treatments on the aorta and liver of obese and non-obese rats.

AIM: To evaluate the impact of the presence and treatment of periodontal disease (PD) and apical periodontitis (AP) on the aorta and liver of obese and non-obese rats. METHODOLOGY: One hundred and forty Wistar rats were divided into two groups, according to the diet administered: normal diet (-n), without obesity; and cafeteria diet (-c), with induced obesity. These groups were divided into seven subgroups according to the specific experimental protocols: naïve control (NC); AP; AP with treatment (APt); PD; PE with treatment (PDt); AP and PD (APPD); and AP and PD with treatment (APPDt). AP and PD lesions were induced for four weeks. Four weeks after treatments, the animals were euthanatized, and the aorta and liver were dissected for histological evaluation. For the comparison of the thickness of the aorta between groups, the Kruskal-Wallis test was used, followed by the Mann-Whitney test. For the analysis of other variables related to the aorta and liver outcomes, logistic regression was carried out. RESULTS: Both PD and AP were associated with the development of histological alterations in the aortic arch, with no significant difference between obese and non-obese animals (p = .17). The aorta thickness was increased significantly (p < .05) with the combination of PD and AP in obese rats (APPDt-c group) compared with the other groups (NC-n, APt-n, APt-c and AP-c). The logistic regression models revealed that the untreated (OR = 7.78; 95%CI = 2.4-25) and treated (OR = 2.9; 95%CI = 1.0-8.4) groups were significantly more likely to have endothelial alterations compared with the control groups (p = .002). Obesity (OR = 16.5; 95%CI = 3.4-81.3) was the only predictor variable of liver steatosis (p < .001). CONCLUSION: Histological alterations in the aortic arch of obese and non-obese rats were observed in the presence of periodontal disease and apical periodontitis. The combination of PD and AP increased the aorta thickness in obese rats. A reduction of vascular endothelial lesions was observed with the treatments of PD and AP.

IL-21 treatment recovers follicular helper T cells and neutralizing antibody production in respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in children under 1 year. RSV vaccines are currently unavailable, and children suffering from multiple reinfections by the same viral strain fail to develop protective responses. Although RSV-specific antibodies can be detected upon infection, these have limited neutralizing capacity. Follicular helper T (Tfh) cells are specialized in providing signals to B cells and help the production and affinity maturation of antibodies, mainly via interleukin (IL) 21 secretion. In this study, we evaluated whether RSV could inhibit Tfh responses. We observed that Tfh cells fail to upregulate IL-21 production upon RSV infection. In the lungs, RSV infection downregulated the expression of IL-21/interleukin-21 receptor (IL-21R) in Tfh cells and upregulated programmed death-ligand 1 (PD-L1) expression in dendritic cells (DCs) and B cells. PD-L1 blockade during infection recovered IL-21R expression in Tfh cells and increased the secretion of IL-21 in a DC-dependent manner. IL-21 treatment decreased RSV viral load and lung inflammation, inducing the formation of tertiary lymphoid organs in the lung. It also decreased regulatory follicular T cells, and increased Tfh cells, B cells, antibody avidity and neutralization capacity, leading to an overall improved anti-RSV humoral response in infected mice. Passive immunization with purified immunoglobulin G from IL-21-treated RSV-infected mice protected against RSV infection. Our results unveil a pathway by which RSV affects Tfh cells by increasing PD-L1 expression on antigen-presenting cells, highlighting the importance of an IL-21-PD-L1 axis for the generation of protective responses to RSV infection.

TNF-mediated alveolar macrophage necroptosis drives disease pathogenesis during respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the major cause of acute bronchiolitis in infants under 2 years old. Necroptosis has been implicated in the outcomes of respiratory virus infections. We report that RSV infection triggers necroptosis in primary mouse macrophages and human monocytes in a RIPK1-, RIPK3- and MLKL-dependent manner. Moreover, necroptosis pathways are harmful to RSV clearance from alveolar macrophages. Additionally, Ripk3-/- mice were protected from RSV-induced weight loss and presented with reduced viral loads in the lungs.Alveolar macrophage depletion also protected mice from weight loss and decreased lung RSV virus load. Importantly, alveolar macrophage depletion abolished the upregulation of Ripk3 and Mlkl gene expression induced by RSV infection in the lung tissue.Autocrine tumor necrosis factor (TNF)-mediated RSV-triggered macrophage necroptosis and necroptosis pathways were also involved in TNF secretion even when macrophages were committed to cell death, which can worsen lung injury during RSV infection. In line, Tnfr1-/- mice had a marked decrease in Ripk3 and Mlkl gene expression and a sharp reduction in the numbers of necrotic alveolar macrophages in the lungs. Finally, we provide evidence that elevated nasal levels of TNF are associated with disease severity in infants with RSV bronchiolitis.We propose that targeting TNF and/or the necroptotic machinery may be valuable therapeutic approaches to reduce the respiratory morbidity caused by RSV infection in young children.

Metastasis of Prostate Adenocarcinoma in the Mandible: Rare Occurrence in Maxillary Bones.

OBJECTIVE: This article describes the case report of a prostate adenocarcinoma in the mandible. BACKGROUND: Prostate adenocarcinoma is a malignant tumor common in men from the fourth decade of life. The occurrence of oral metastatic lesions is rare. CASE REPORT: A 78-year-old male patient was referred to the oral and maxillofacial surgery service of the Pontifical Catholic University of Rio Grande do Sul for complaints of painless volume increase in the mandible. The diagnosis through the association of clinical, radiographic, and histopathological examination with the patient's health history determined that the lesion was prostatic adenocarcinoma metastasis. CONCLUSION: Despite the rare occurrence of metastases in the oral region, the dental surgeon should be aware of the possibility for correct diagnostic conduction and, subsequently, the institution of treatment in the early stages of disease.

Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response.

Severe respiratory syncytial virus (RSV) infection is a major cause of morbidity and mortality in infants <2 years-old. Here we describe that high-fiber diet protects mice from RSV infection. This effect was dependent on intestinal microbiota and production of acetate. Oral administration of acetate mediated interferon-ß (IFN-ß) response by increasing expression of interferon-stimulated genes in the lung. These effects were associated with reduction of viral load and pulmonary inflammation in RSV-infected mice. Type 1 IFN signaling via the IFN-1 receptor (IFNAR) was essential for acetate antiviral activity in pulmonary epithelial cell lines and for the acetate protective effect in RSV-infected mice. Activation of Gpr43 in pulmonary epithelial cells reduced virus-induced cytotoxicity and promoted antiviral effects through IFN-ß response. The effect of acetate on RSV infection was abolished in Gpr43-/- mice. Our findings reveal antiviral effects of acetate involving IFN-ß in lung epithelial cells and engagement of GPR43 and IFNAR.

Cross Talk between Apical Periodontitis and Metabolic Disorders: Experimental Evidence on the Role of Intestinal Adipokines and Akkermansia muciniphila.

INTRODUCTION: Infection and dysbiosis present a close relationship with metabolic diseases although the influence of apical periodontitis (AP) in this context needs further investigation. This study evaluated the influence of AP in a rat model of metabolic syndrome induced by 10% fructose supplementation. METHODS: Male Wistar rats were used. Animals that received a high-fructose diet (HFD, n = 30) or filtered water (control, n = 30) were subdivided into the following groups: (1) without induction of AP (no AP, n = 10 each), (2) with AP induction 2 weeks before euthanasia (AP 14 days, n = 10 each), and (3) with AP induction 4 weeks before euthanasia (AP 28 days, n = 10 each). RESULTS: HFD triggered metabolic syndrome, as indicated by the induction of overweight and hyperglycemia, besides polydipsia, regardless of the AP induction. Serum or intestinal tumor necrosis factor, interleukin 1 beta, and interleukin 6 levels were undetectable, regardless of the experimental group. Serum leptin and adiponectin levels were significantly elevated in the HFD group without AP induction. The intestinal levels of leptin were significantly increased in the groups with 28 days of AP induction despite HFD. A significant elevation of liver glutathione levels was observed in animals submitted to HFD and AP for 14 days. AP induction (14 or 28 days) led to pulp and periapical tissue inflammation without any influence of HFD. Either HFD or AP induction led to dysbiosis, as indicated by a significant reduction of fecal A. muciniphila expression. CONCLUSIONS: We provide novel evidence that AP can have systemic impacts on metabolic disorders, likely by modulating intestinal metabolism and microbiota.

Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis based on a case reports systematic survey / Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis based on a case reports systematic survey

Abstract Introduction: Solitary plasmacytoma is a rare malignant tumor of plasma cells with no evidence of systemic proliferation. There are two known subtypes: extramedullary solitary plasmacytoma and solitary bone plasmacytoma. The etiology is still unknown. Both lesions present a risk of progression to multiple myeloma. A number of approaches have been used for treatment of solitary plasmacytoma. Objective: To carry out a systematic review of the case reports described in the literature, focusing on therapeutic and prognostic aspects. Methods: A search of clinical case reports was performed in the PubMed database using Mesh Terms related to "plasmacytoma" under the following criteria: type of study (case report), articles in English language, conducted in humans, with no publication date limits. Results: Of the 216 articles found, only 21 articles met the pre-established inclusion criteria. Conclusion: The occurrence of solitary bone plasmacytoma in the bones of the face is a rare condition prevalent between the 4th and 6th decades of life, located in the posterior region of the mandible in most cases. Histopathological examination and systemic investigation are mandatory for confirmation of diagnosis.

Resumo: Introdução: O plasmocitoma solitário é um tumor maligno raro de células plasmáticas sem evidência de proliferação sistêmica e engloba dois subtipos: plasmocitoma solitário extramedular e plasmocitoma solitário ósseo. A etiologia ainda é desconhecida. Ambas as lesões apresentam risco de progressão para mieloma múltiplo. Uma série de abordagens tem sido usada para seu tratamento. Objetivo: Realizar uma revisão sistemática da literatura com enfoque nos aspectos terapêuticos e prognósticos. Método: Realizou-se uma busca de relatos de caso clínico na base de dados PubMed com termos de busca relacionados com "plasmocitoma" sob os seguintes critérios: tipo de estudo (relato de caso), artigos na língua inglesa, estudos realizados apenas em humanos, sem limites de data de publicação. Resultados: Dos 216 artigos encontrados, apenas 21 preencheram os critérios de inclusão pré-estabelecidos. Conclusão: A ocorrência de plasmocitoma solitário ósseo nos ossos da face é uma condição rara prevalente entre a 4a e a 6a décadas de vida, localizada na região posterior de mandíbula na maioria dos casos. O exame histopatológico e a investigação sistêmica são mandatórios para confirmação do diagnóstico.

The use of cytopathology to identify disturbances in oral squamous cell carcinoma at early stage: A case report.

Early detection of oral squamous cell carcinoma (OSCC) is a challenge for oral surgeons, as clinical features are not always classical. Cytopathological assays can help identify alterations at the cellular level. This article reports a case of OSCC in a young male adult without exposure to classical risk factors. The histopathological examination showed a micro invasive carcinoma invading the connective tissue. Cytopathological results showed a higher percentage of cells in deeper epithelial layers; the cytomorphometric examination revealed a nuclear/cytoplasmic ratio of 0.14; the mean number of Nucleolar Organiser Regions which have a high affinity for silver (AgNOR) per nucleus was 2.86, and the mean percentage of nuclei with >2 AgNOR was 58%. The micronucleus test found 3 micronucleated cells and several metanuclear aberrations. These findings support the hypothesis that cytological examination is an important tool to identify early changes in oral smears and thus help in the early clinical detection of suspicious malignant oral lesions that should be more rigorously followed.

Vaccination with RSV M209-223 peptide promotes a protective immune response associated with reduced pulmonary inflammation.

Respiratory syncytial virus (RSV) is the most common etiologic agent in severe infections of the lower respiratory tract in children with a high mortality rate. However, there are still no licensed vaccines for RSV. In this study, we investigated a putative vaccine based on M209-223 peptide. Mice vaccinated with M209-223 peptide expanded M209-223-specific effector CD4+ T cells upon infection. Vaccination resulted in increased numbers of regulatory T cells (Treg) and Th1 cells, and decreased numbers of Th2 cells. In addition, vaccination with M209-223 peptide, protected mice from infection and prevented lung inflammation, leading to increase in IL-10 and IFN-γ production by lung CD4+ T cells. Treg depletion with anti-CTLA4 antibodies abrogated protection induced by peptide vaccination. Our results support vaccination with M209-223 peptide as an important strategy to generate protection, both systemic and local, by memory RSV-specific CD4+ T cells in mice. Contrarily to inactivated RSV particles, M209-223 peptide vaccination is capable of not only promoting viral clearance, but also reducing inflammatory processes in lungs upon infection.

Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis based on a case reports systematic survey.

INTRODUCTION: Solitary plasmacytoma is a rare malignant tumor of plasma cells with no evidence of systemic proliferation. There are two known subtypes: extramedullary solitary plasmacytoma and solitary bone plasmacytoma. The etiology is still unknown. Both lesions present a risk of progression to multiple myeloma. A number of approaches have been used for treatment of solitary plasmacytoma. OBJECTIVE: To carry out a systematic review of the case reports described in the literature, focusing on therapeutic and prognostic aspects. METHODS: A search of clinical case reports was performed in the PubMed database using Mesh Terms related to "plasmacytoma" under the following criteria: type of study (case report), articles in English language, conducted in humans, with no publication date limits. RESULTS: Of the 216 articles found, only 21 articles met the pre-established inclusion criteria. CONCLUSION: The occurrence of solitary bone plasmacytoma in the bones of the face is a rare condition prevalent between the 4th and 6th decades of life, located in the posterior region of the mandible in most cases. Histopathological examination and systemic investigation are mandatory for confirmation of diagnosis.

Does Surgical Fragmentation of Odontogenic Keratocystic Capsule Interfere With the Recurrence Rate?

PURPOSE: We hypothesized that fragmentation of the cystic capsule during surgery would influence the recurrence rate of odontogenic keratocysts (OKCs) regardless of the treatment modality chosen. MATERIALS AND METHODS: We reviewed, in a retrospective study, cases diagnosed as OKCs on histopathologic examination at the oral pathology department between 1991 and 2013. Fragmentation data were obtained from the records of the oral surgical department. RESULTS: Fragmentation of the capsules of OKCs during surgery did not affect recurrence, irrespective of the chosen treatment modality. The addition of techniques such as cryotherapy lowered the risk of recurrence of OKCs (P = .013) compared with after enucleation alone. Furthermore, patients with associated nevoid basal cell carcinoma syndrome had a greater recurrence rate than that of those with no associated syndrome (P = .033). CONCLUSIONS: Fragmentation of the cystic capsule does not play an important role in the rate of OKC recurrence. The rate of recurrence can be modified by using additional strategies such as cryotherapy.

Effect of low-level laser therapy on tissue repair after dental extraction in rats administered zoledronic acid and dexamethasone.

Bisphosphonates (BPs) are being increasingly used for the treatment of metabolic and oncological pathologies involving the skeletal system. Because of the severity of the BP associated osteonecrosis of the jaws, the difficulties of treatment, and patient discomfort, additional support methods for their management are needed. Laser therapy has an easy handling, photobiostimulator effect on tissues healing, so it can be considered a preferred therapy. The aim of this study was to evaluate the influence of low-level laser therapy in the 685- and 830-nm wavelength in the healing process of the bone and soft tissues in rats under BP therapy [zoledronic acid (ZA)] and dexamethasone concomitantly that underwent a surgery for the extraction of upper molars. There were statistically significant differences in the clinical evaluation of the wound and the weight of the animals. Regarding the histological evaluation, it was possible to observe the different maturations of the healing stage between groups. The effect of drug therapy with ZA and dexamethasone in the bone tissue repair process induces osteonecrosis of the jaw in rats and slows down the healing process. In the laser groups, at the stipulated dosimetry, a positive influence on the bone and soft tissue repair process was observed.

Prolonged survival of allografts induced by mycobacterial Hsp70 is dependent on CD4+CD25+ regulatory T cells.

BACKGROUND: Heat shock proteins (Hsps) are stress induced proteins with immunomodulatory properties. The Hsp70 of Mycobacterium tuberculosis (TBHsp70) has been shown to have an anti-inflammatory role on rodent autoimmune arthritis models, and the protective effects were demonstrated to be dependent on interleukin-10 (IL-10). We have previously observed that TBHsp70 inhibited maturation of dendritic cells (DCs) and induced IL-10 production by these cells, as well as in synovial fluid cells. METHODOLOGY/PRINCIPAL FINDINGS: We investigated if TBHsp70 could inhibit allograft rejection in two murine allograft systems, a transplanted allogeneic melanoma and a regular skin allograft. In both systems, treatment with TBHsp70 significantly inhibited rejection of the graft, and correlated with regulatory T cells (Tregs) recruitment. This effect was not tumor mediated because injection of TBHsp70 in tumor-free mice induced an increase of Tregs in the draining lymph nodes as well as inhibition of proliferation of lymph node T cells and an increase in IL-10 production. Finally, TBHsp70 inhibited skin allograft acute rejection, and depletion of Tregs using a monoclonal antibody completely abolished this effect. CONCLUSIONS/SIGNIFICANCE: We present the first evidence for an immunosuppressive role for this protein in a graft rejection system, using an innovative approach--immersion of the graft tissue in TBHsp70 solution instead of protein injection. Also, this is the first study that demonstrates dependence on Treg cells for the immunosuppressive role of TBHsp70. This finding is relevant for the elucidation of the immunomodulatory mechanism of TBHsp70. We propose that this protein can be used not only for chronic inflammatory diseases, but is also useful for organ transplantation management.

HspBP1 levels are elevated in breast tumor tissue and inversely related to tumor aggressiveness.

HspBP1 is a co-chaperone that binds to and regulates the chaperone Hsp70 (Hsp70 is used to refer to HSPA1A and HSPA1B). Hsp70 is known to be elevated in breast tumor tissue, therefore the purpose of these studies was to quantify the expression of HspBP1 in primary breast tumors and in serum of these patients with a follow-up analysis after 6 to 7 years. Levels of HspBP1, Hsp70, and anti-HspBP1 antibodies in sera of breast cancer patients and healthy individuals were measured by enzyme-linked immunosorbent assay. Expression of HspBP1 was quantified from biopsies of tumor and normal breast tissue by Western blot analysis. The data obtained were analyzed for association with tumor aggressiveness markers and with patient outcome. The levels of HspBP1 and Hsp70 were significantly higher in sera of patients compared to sera of healthy individuals. HspBP1 antibodies did not differ significantly between groups. HspBP1 levels were significantly higher in tumor (14.46 ng/microg protein, n = 51) compared to normal adjacent tissue (3.17 ng/microg protein, n = 41, p < 0.001). Expression of HspBP1 was significantly lower in patients with lymph node metastasis and positive for estrogen receptors. HspBP1 levels were also significantly lower in patients with a higher incidence of metastasis and death following a 6 to 7-year follow-up. The HspBP1/Hsp70 molar ratio was not associated with the prognostic markers analyzed. Our results indicate that low HspBP1 expression could be a candidate tumor aggressiveness marker.

Odontogenic cysts: analysis of 680 cases in Brazil.

The purpose of this study was to evaluate the prevalence of 680 odontogenic cysts diagnosed in Porto Alegre, RS, Brazil, and to compare results with findings in the literature. Data of odontogenic cysts diagnosed from 1985 to 2005 were collected from the files of the Oral Pathology Laboratory of Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil, and entered in a standardized form for later comparisons. The most prevalent odontogenic cysts were radicular (72.50%), dentigerous (22.20%) and residual (4.26%) cysts. The mandible of white patients was the anatomic site and ethnic group most frequently affected by this disease. Four of the six types of cysts were more frequent in the second and fourth decades of life, and no significant differences were found between sexes in the diagnosis of odontogenic cysts. In conclusion, the prevalence of odontogenic cysts was similar to that reported in the literature, which shows that inflammatory cysts are the most frequent.