Negative terpinen-4-ol modulate potentially malignant and malignant lingual lesions induced by 4-nitroquinoline-1-oxide in rat model.

Our aim was to verify the modulative TP-4-ol capacity in 4-nitroquinoline-1-oxide induced oral rat cancer. The stereoisomers of TP-4-ol were used against the human tongue squamous cell line and the negative stereoisomer showed lower IC50. Thirty-one Holtzman rats (120-130 g) were cancer-induced by 4-nitroquinoline-1-oxide (4-NQO/8 weeks/25 ppm) and 32 Holtzman rats (120-130 g) were used to healthy and TP-4-ol toxicity experiments. Six groups were used, healthy, 0.1nL/g of TP-4-ol, 8nL/g of TP-4-ol, 4-NQO, 4-NQO + 0.1nL/g of TP-4-ol, and 4-NQO + 8nL/g of TP-4-ol. We performed the toxicity analysis by biochemical and histopathological analysis. The biochemistry analysis includes alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate transaminase (AST), urea, and creatinine and the histopathology analysis includes the liver, kidney, lung, and spleen. Specifically, for malign modulation, we performed a macroscopic and microscopic analysis. The group exposed to 0.1nL/g of TP-4-ol demonstrated a reduced risk of malignancy in dysplasia considering the criteria of architecture and cytology. Similarly, a drop of percentual rats with SCC diagnosis was observed in 4-NQO + 0.1nL/g (41.6%) when compared to 4-NQO (87.5%). Moreover, the 4-NQO group presented a median of 2.62 SCC/rat and the 4-NQO + 0.1nL/g demonstrated a median of 0.75 SCC/rat. For toxicity analysis, 4-NQO + 0.1nL/g showed focal necrosis in the kidney and 4-NQO showed lung hemorrhagic areas. The concentration of 0.1nL/g was more effective in reducing the tongue induction of potentially malignant and malignant lesions by 4-NQO. A kidney toxicity was observed in healthy animals exposed to 0.1nL/g of TP-4-ol. The negative isoform of terpinen-4-ol negatively modulates the development of potentially malignant and malignant lesions in rats (Rattus nonverdicts albinos, Holtzman) exposed to 4-NQO. (-)-Terpinen-4-ol reduced the mice percentual with squamous cell carcinoma, 87.5 to 41.6%, and decreased the cancer/rat ratio of 2.62 in 4-NQO to 0.75 in 4-NQO + 0.1nL/g. This represents 52.4% by group and 71.3% in the cancer/rat ratio.

Prognostic value of lymphovascular and perineural invasion in squamous cell carcinoma of the tongue.

OBJECTIVE: The objective of this study was to investigate the association between survival rate and lymphovascular invasion (LVI) and perineural invasion (PNI) in the tumor invasive front (TIF) of squamous cell carcinoma of the tongue (TSCC). STUDY DESIGN: Seventy patients with TSCC were included. The retrospective analysis included demographic, clinical, and histopathologic data. Tissue blocks containing the TIF were stained with anti-α-smooth muscle actin and anti-S100 to detect LVI and PNI, respectively. Overall survival (OS) and disease-specific survival (DSS) were assessed using Pearson's chi-square test, Kaplan-Meier method, and Cox regression. RESULTS: LVI and PNI were detected in 61.4% and 78.6% of the TSCC samples at the TIF, respectively. LVI and PNI were present in 54.3% of the cases and were associated with advanced clinical stage, lymph node resection, metastatic nodes, and lower survival (P < .05). The 5-year OS and DSS rates were 44% and 52%, respectively. Multivariate analysis showed that primary tumors >3.0 cm (hazard ratio = 4.29; P = .004) and a concomitant presence of LVI and PNI at the TIF (hazard ratio = 4.0; P = .012) were independent predictors for worse DSS. CONCLUSION: LVI and PNI, identified by immunostaining at the TIF, are potential prognostic markers of TSCC.

Evaluation of Alveolar Bone Quality: Correlation Between Histomorphometric Analysis and Lekholm and Zarb Classification.

OBJECTIVES: This study evaluated the bone quality of the maxilla and mandible by using the classification proposed by Lekholm and Zarb (L & Z) and histomorphometry. METHODS: Sixty edentulous areas were evaluated. The classification by L & Z was obtained through the evaluation of periapical and panoramic radiographs associated with the surgeon's tactile perception during milling and implant installation. Before implant installation, bone biopsies of standardized sizes were performed for histological evaluation. RESULTS: Type III bone quality was more frequent in the posterior (73.33%) and anterior (73.33%) maxilla, whereas type II bone quality was more frequent in the posterior (53.33%) and anterior (60.00%) mandible. Through histometry, statistical difference was observed for the amount of bone tissue of the posterior region of the maxilla in relation to the anterior and posterior regions of the mandible (P ≤ 0.043). However, there was no difference in osteocyte counts between alveolar regions (P = 0.2946). In the female gender, the age showed a low positive correlation with the L & Z classification (rho = 0.398; P = 0.006) and in the male gender, a moderate negative correlation was observed (rho = -0.650, P = 0.016). CONCLUSIONS: Both methods detected differences in the bone quality of the alveolar regions of the maxilla/mandible and that the classification by L & Z is a reliable method, since it was consistent with histomorphometry, considered the "gold standard" method for the evaluation of bone quality and greater bone density was observed in older men.

Aqueous extract of Paullinia cupana attenuates renal and hematological effects associated with ketoprofen.

This study aimed to evaluate the effect of aqueous extract of Paullinia cupana (AEG) against ketoprofen side effects, through biochemical, hematological, and histological parameters. AEG showed antioxidant activity in the DPPH• scavenging (IC50  = 17.00 ± 1.00 µg/ml) and HPLC analysis revealed that this extract is constituted by antioxidants (caffeine, catechins, theobromine, and polyphenols). In vivo experiments in female Wistar rats demonstrated that alterations in urea, creatinine, and uric acid levels promoted (p < .05) by ketoprofen were reversed when AEG was co-administered. Ketoprofen significantly decreased the catalase levels of animal tissues (p < .05), which were restored when AEG was co-administered with the mentioned drug. Histological analysis showed that AEG protected tissues from damages caused by ketoprofen. Moreover, AEG reestablished the number of white blood cells, which had decreased when ketoprofen was administered. In conclusion, this study suggested that the association between ketoprofen and AEG may be an alternative to reduce health damages caused by this drug. PRACTICAL APPLICATIONS: Paullinia cupana, popularly known as guaraná, is commonly consumed as a beverage in Brazil and exhibits pharmacological and beneficial effects to humans. Ketoprofen is an efficacious drug employed in the treatment of inflammatory processes. However, this drug can cause several side effects in humans. Thus, the usage of natural products and plant extracts that can reduce such undesirable effects consists in a valuable strategy to be applied in therapeutic interventions.

Transient Foxp3(+) regulatory T-cell depletion enhances protective Th1/Th17 immune response in murine sporotrichosis caused by Sporothrix schenckii.

The role of regulatory T cells (Tregs) on protective immunity in fungal infections, is controversial. Sporotrichosis is an emerging and worldwide-distributed subcutaneous mycosis caused by various related thermodimorphic fungi of the genus Sporothrix. Previously, we showed an elevated percent of Tregs around 21 days post-infection (dpi) in C57BL/6 mice infected with either Sporothrix schenckii or Sporothrix brasiliensis, but the effect of these cells in the ongoing infection was not evaluated. Here, we aim to characterize the role of Foxp3+ Tregs in a subcutaneous S. schenckii infection model. The flow cytometric analyses showed that S. schenckii infection elicited an expansion of a splenic CD4+Foxp3+ population, including a subset of Helioslow+ after ex vivo stimulation with S. schenckii-heat killed yeast. Depletion of Tregs in DEREG mice revealed a reduction of fungal burden in the skin and systemically in liver and kidneys, associated with enhanced Th1 and Th17 responses. Altogether, our results reveal for the first time that Tregs depletion in ongoing S. schenckii infection improves the protective antifungal immunity and these data suggest that Tregs modulation could be explored as a potential therapeutic strategy in sporotrichosis.

Possible association of periodontal disease with oral cancer and oral potentially malignant disorders: a systematic review.

Background: Periodontitis has been associated with several systemic diseases and medical conditions, including oral cancer (OC). However, most studies reporting an association between OC and periodontal disease have used different clinical and radiographic criteria to define periodontal disease. This review aimed to evaluate the currently available evidence to determine an association between periodontal disease (extension and severity), OC, and oral potentially malignant disorders (OPMDs).Material and methods: A systematic search of studies published up to August 2018 was performed following the PRISMA guidelines in the electronic databases MEDLINE (PubMed) and COCHRANE (OVID). A methodological evaluation was made using the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) checklist.Results: Eight studies (case-control, cross-sectional and cohort) were included. An increased clinical attachment loss, plaque index, bleeding on probing, and radiographic bone loss was found in patients with OC and OPMDs. Differences in the methodological characteristics, case definition used for periodontal diseases, and OC location did not allow estimating the odds ratio required to conduct a meta-analysis.Conclusion: Some studies suggest a positive relationship between periodontal disease, OC, and OPMDs; however, the currently available evidence is insufficient to draw solid conclusions.

Down-regulation of TUFM impairs host cell interaction and virulence by Paracoccidioides brasiliensis.

The genus Paracoccidioides consist of dimorphic fungi geographically limited to the subtropical regions of Latin America, which are responsible for causing deep systemic mycosis in humans. However, the molecular mechanisms by which Paracoccidioides spp. causes the disease remain poorly understood. Paracoccidioides spp. harbor genes that encode proteins involved in host cell interaction and mitochondrial function, which together are required for pathogenicity and mediate virulence. Previously, we identified TufM (previously known as EF-Tu) in Paracoccidioides brasiliensis (PbTufM) and suggested that it may be involved in the pathogenicity of this fungus. In this study, we examined the effects of downregulating PbTUFM using a silenced strain with a 55% reduction in PbTUFM expression obtained by antisense-RNA (aRNA) technology. Silencing PbTUFM yielded phenotypic differences, such as altered translation elongation, respiratory defects, increased sensitivity of yeast cells to reactive oxygen stress, survival after macrophage phagocytosis, and reduced interaction with pneumocytes. These results were associated with reduced virulence in Galleria mellonella and murine infection models, emphasizing the importance of PbTufM in the full virulence of P. brasiliensis and its potential as a target for antifungal agents against paracoccidioidomycosis.

Salivary glands: a clinical-histopathological study / Glándulas salivales: un estudio clínico-histopatológico / Glândulas salivares: um estudo clínico-histopatológico

Abstract Introduction and objective: The diseases that affect the salivary glands cover a wide range of conditions and etiologies, including infectious, inflammatory, immunological or neoplastic pathologies. The objective of this study was to identify the most frequent salivary gland diseases diagnosed in the School of Dentistry of Araraquara of the São Paulo State University (FOAr-UNESP). Materials and methods: This retrospective descriptive study included all cases of salivary gland diseases diagnosed between 2009 and 2013. In total, 2,236 clinical records of the Oral Medicine Service and 1,217 histopathological reports of the Histopathological Diagnosis Service were evaluated. Results: We identified 254 patients diagnosed with salivary gland disease, predominantly women (1.5 F / M). The most frequent diagnoses were mucocele (38.6%), sialolithiasis (6.7%), sialadenitis (5.1%), ranula (4.3%), Sjögren's syndrome (2.8%), pleomorphic adenoma (1.2%) and mucoepidermoid carcinoma (1.2%). The most frequent histopathological diagnosis was the phenomenon of extravasation of mucus (85.2%). A common clinical finding was xerostomia (39%), mainly in patients treated with antihypertensive (42.4%), psychiatric (35.3%), anti-inflammatory (20.2%) and drugs for the treatment of gastric ulcers (13.1%). Conclusions: Our findings show the importance of a careful diagnosis, not only for neoplastic lesions, but also for pathologies of autoimmune, inflammatory and traumatic origin, which make up a greater number of cases. In addition, oral health professionals should be aware of the high frequency of xerostomia and its association with the use of certain medications, due to its negative impact on the quality of life of those suffering from this condition.

Resumen Introducción y objetivo: Las enfermedades que afectan a las glándulas salivales abarcan una amplia gama de condiciones y etiologías, incluyendo patologías infecciosas, inflamatorias, inmunológicas o neoplásicas. El objetivo de este estudio fue identificar las enfermedades más frecuentes de las glándulas salivales diagnosticadas en la Facultad de Odontología de Araraquara de la Universidad Estatal Paulista (FOAr-UNESP). Materiales y métodos: Este estudio descriptivo retrospectivo, incluyó todos los casos de enfermedades de glándulas salivales diagnosticados entre los años 2009 a 2013. En total se evaluaron 2,236 registros clínicos del Servicio de Medicina Oral y 1,217 informes histopatológicos del Servicio de Diagnóstico Histopatológico. Resultados: Se identificaron 254 enfermedades de las glándulas salivales, predominantemente en mujeres (1.5 F / M). Los diagnósticos más frecuentes fueron mucocele (38,6%), sialolitiasis (6,7%), sialadenitis (5,1%), ránula (4,3%), síndrome de Sjögren (2,8%), adenoma pleomórfico (1,2%) y carcinoma mucoepidermoide (1.2%). El diagnóstico histopatológico más frecuente fue el fenómeno de extravasación de moco (85.2%). Un hallazgo clínico frecuente fue la xerostomía (39%), principalmente en pacientes en tratamiento con medicamentos antihipertensivos (42,4%), psiquiátricos (35,3%), antiinflamatorios (20,2%) y fármacos para el tratamiento de úlceras gástricas (13,1%). Conclusiones: Nuestros hallazgos muestran la importancia del diagnóstico cuidadoso, no sólo de las lesiones neoplásicas, sino también de las patologías de origen autoinmune, inflamatorio y traumático, que constituyen un mayor número de casos. Además, los profesionales de la salud bucal deben conocer la alta frecuencia de la xerostomía y su asociación con el uso de ciertos medicamentos, debido a su impacto negativo en la calidad de vida de las personas que padecen esta afección.

Resumo Introdução e objetivo: As doenças que afetam as glândulas salivares cobrem uma ampla gama de condições e etiologias, incluindo patologias infecciosas, inflamatórias, imunológicas ou neoplásicas. O objetivo deste estudo foi identificar as doenças mais frequentes das glândulas salivares diagnosticadas na Faculdade de Odontologia de Araraquara da Universidade Estadual Paulista (FOAr-UNESP). Materiais e métodos: Este estudo retrospectivo descritivo incluiu todos os casos de doenças da glândula salivar diagnosticados entre 2009 e 2013. No total, foram avaliados 2,236 prontuários clínicos do Serviço de Medicina Oral e 1,217 laudos histopatológicos do Serviço de Diagnóstico Histopatológico. Resultados: Foram identificadas 254 doenças das glândulas salivares, predominantemente mulheres (1,5 F/M). Os diagnósticos mais frequentes foram mucocele (38,6%), sialolitíase (6,7%), sialadenite (5,1%), ranula (4,3%), síndrome de Sjögren (2,8%), adenoma pleomórfico (1,2%) e carcinoma mucoepidermóide (1,2%). O diagnóstico histopatológico mais freqüente foi o fenômeno de extravasamento de muco (85.2%). Um achado clínico comum foi a xerostomia (39%), principalmente em pacientes tratados com anti-hipertensivos (42,4%), psiquiátricos (35,3%), anti-inflamatórios (20,2%) e medicamentos para tratamento de úlceras gástricas (13,1%). Conclusões: Nossos achados mostram a importância de um diagnóstico cuidadoso, não só das lesões neoplásicas, mas também de patologias de origem autoimune, inflamatória e traumática, que compõem um maior número de casos. Além disso, os profissionais de saúde bucal devem estar cientes da alta frequência de xerostomia e sua associação com o uso de certos medicamentos, devido ao seu impacto negativo na qualidade de vida daqueles que sofrem dessa condição.

Paracoccidioides brasiliensis 14-3-3 protein is important for virulence in a murine model.

The Paracoccidioides brasiliensis strain downregulated the expression of adhesin Pb14-3-3 (Pb14-3-3 aRNA) was evaluated in a murine model of paracoccidioidomycosis (PCM). Pb14-3-3 aRNA displays attenuated virulence and triggered the formation of fewer granulomas by lowering the fungal burden in the lungs. Additionally, the Pb14-3-3 aRNA showed more elongated yeast cells and less ability to induce pneumocytes apoptosis in vitro. Our results show that 14-3-3 is an important virulence factor in P. brasiliensis-induced pulmonary infection.

Experimental sporotrichosis in a cyclophosphamide-induced immunosuppressed mice model.

This report describes a model of host resistance for Sporothrix schenckii, an opportunistic fungi in immunosuppressed mice with cyclophosphamide (CY) to be used in studies of immunotoxicology and immunopharmacology. Two doses of CY were administered intraperitoneally: 200 mg/kg and a booster of 150 mg/kg at 9-day intervals. Three days after the first dose of CY the animals were infected subcutaneously with 1.8 × 108 yeast/ml (S. schenckii ATCC 16345). At 7 and 14 days post-infection, the animals were euthanized and analyzed the fungal load by unit forming colony count in the spleen and popliteal lymph nodes. The relative weight of thymus and spleen, splenic index, the frequency of T and B cells in spleen by flow cytometry, the hind paw inflammation index and cytokine (interleukin [IL]-17, IL-10, and interferon [IFN]-γ) profile were measured. Histopathological studies of the spleen and the hind paw were also assessed. The immunosuppression status was confirmed at the evaluated days by reduction of relative weight of thymus, reduction of the splenic white pulp, the population of B and T lymphocytes, and the cytokine profile in the treated mice with CY in comparison with nontreated groups, associated to higher fungal load in hind paw and spleen in the infected mice. The described model reveals an increasing in susceptibility to infection and severity when associated with immunosuppression. This model can serve as a reference for studies of S. schenckii host resistance in pharmaceutical and toxicological studies.

In vivo antileishmanial activity and histopathological evaluation in Leishmania infantum infected hamsters after treatment with a furoxan derivative.

N-oxide derivatives compounds such as furoxan and benzofuroxan are promising scaffolds for designing of new antileishmanial drugs. A series of furoxan (1,2,5-oxadiazole 2-N-oxide) (compounds 4a-b, and 14a-f) and benzofuroxan (benzo[c][1,2,5]oxadiazole1-N-oxide) (compounds 8a-c) derivatives were evaluated against in vitro cultured L. infantum promastigotes and amastigotes. The compounds exhibited activity against promastigote and intracellular amastigote forms with EC50 values ranging from 2.9 to 71.2µM and 2.1 to 18.2µM, respectively. The most promising compound, 14e, showed good antileishmanial activity (EC50=3.1µM) against intracellular amastigote forms of L. infantum with a selectivity index, based on murine macrophages (SI=66.4), almost 3-times superior to that presented by the standard drug amphotericin B (AmpB). The efficacy of 14e to eliminate the parasites in vivo was also demonstrated. Treatment of L. infantum-infected hamsters with compound 14e at 3.0mg/Kg/day led to a meaningful reduction of parasite load in spleen (49.9%) and liver (54.2%), respectively; these data were corroborated by histopathological analysis, which also revealed reduction in the number of inflammatory cells in the liver of the treated animals. Moreover, histological analysis of the spleen and kidney of treated animals did not reveal alterations suggestive of toxic effects. The parasite load reduction might be related to NO production, since this molecule is a NO-donor. We observed neither side effects nor elevation of hepatic/renal biomarker levels in the plasma. The data herein presented suggest that the compound should be considered in the development of new drugs for treatment of visceral leishmaniasis.

Comparative efficacy and toxicity of two vaccine candidates against Sporothrix schenckii using either Montanide™ Pet Gel A or aluminum hydroxide adjuvants in mice.

Sporotrichosis is an important zoonosis in Brazil and the most frequent subcutaneous mycosis in Latin America, caused by different Sporothrix species. Currently, there is no effective vaccine available to prevent this disease. In this study, the efficacy and toxicity of the adjuvant Montanide™ Pet Gel A (PGA) formulated with S. schenckii cell wall proteins (ssCWP) was evaluated and compared with that of aluminum hydroxide (AH). Balb/c mice received two subcutaneous doses (1st and 14th days) of either the unadjuvanted or adjuvanted vaccine candidates. On the 21st day, anti-ssCWP antibody levels (ELISA), the phagocytic index, as well as the ex vivo release of IFN-γ, IL-4, and IL-17 by splenocytes and IL-12 by peritoneal macrophages were assessed. Cytotoxicity of the vaccine formulations was evaluated in vitro and by histopathological analysis of the inoculation site. Both adjuvanted vaccine formulations increased anti-ssCWP IgG, IgG1, IgG2a, and IgG3 levels, although IgG2a levels were higher in response to PGA+CWP100, probably contributing to the increase in S. schenckii yeast phagocytosis by macrophages in the opsonophagocytosis assay when using serum from PGA+CWP100-immunized mice. Immunization with AH+CWP100 led to a mixed Th1/Th2/Th17 ex vivo cytokine release profile, while PGA+CWP100 stimulated a preferential Th1/Th2 profile. Moreover, PGA+CWP100 was less cytotoxic in vitro, caused less local toxicity and led to a similar reduction in fungal load in the liver and spleen of S. schenckii- or S. brasiliensis-challenged mice as compared with AH+CWP100. These results suggest that PGA may be an effective and safe adjuvant for a future sporotrichosis vaccine.

The NLRP3 inflammasome contributes to host protection during Sporothrix schenckii infection.

Sporotrichosis is a mycosis caused by fungi from the Sporothrix schenckii species complex, whose prototypical member is Sporothrix schenckii sensu stricto. Pattern recognition receptors (PRRs) recognize and respond to pathogen-associated molecular patterns (PAMPs) and shape the following adaptive immune response. A family of PRRs most frequently associated with fungal recognition is the nucleotide-binding oligomerization domain-like receptor (NLR). After PAMP recognition, NLR family pyrin domain-containing 3 (NLRP3) binds to apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 to form the NLRP3 inflammasome. When activated, this complex promotes the maturation of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 and cell death through pyroptosis. In this study, we aimed to evaluate the importance of the NLRP3 inflammasome in the outcome of S. schenckii infection using the following three different knockout (KO) mice: NLRP3-/- , ASC-/- and caspase-1-/- . All KO mice were more susceptible to infection than the wild-type, suggesting that NLRP3-triggered responses contribute to host protection during S. schenckii infection. Furthermore, the NLRP3 inflammasome appeared to be critical for the ex vivo release of IL-1ß, IL-18 and IL-17 but not interferon-γ. Additionally, a role for the inflammasome in shaping the adaptive immune response was suggested by the lower frequencies of type 17 helper T (Th17) cells and Th1/Th17 but not Th1 cells in S. schenckii-infected KO mice. Overall, our results indicate that the NLRP3 inflammasome links the innate recognition of S. schenckii to the adaptive immune response, so contributing to protection against this infection.

Oral verruciform xanthoma: a case report and literature review.

Oral verruciform xanthoma represents an uncommon entity, which affects mainly oral mucosa. This paper presents the major clinical and histological features of oral verruciform xanthoma and reports a case on the tongue. The differential diagnosis and a literature review are also provided in light of recent information.

Evaluation of antimalarial activity and toxicity of a new primaquine prodrug.

Plasmodium vivax is the most prevalent of the five species causing malaria in humans. The current available treatment for P. vivax malaria is limited and unsatisfactory due to at least two drawbacks: the undesirable side effects of primaquine (PQ) and drug resistance to chloroquine. Phenylalanine-alanine-PQ (Phe-Ala-PQ) is a PQ prodrug with a more favorable pharmacokinetic profile compared to PQ. The toxicity of this prodrug was evaluated in in vitro assays using a human hepatoma cell line (HepG2), a monkey kidney cell line (BGM), and human red blood cells deficient in the enzyme glucose-6-phosphate-dehydrogenase (G6PD). In addition, in vivo toxicity assays were performed with rats that received multiple doses of Phe-Ala-PQ to evaluate biochemical, hematological, and histopathological parameters. The activity was assessed by the inhibition of the sporogonic cycle using a chicken malaria parasite. Phe-Ala-PQ blocked malaria transmission in Aedes mosquitoes. When compared with PQ, it was less cytotoxic to BGM and HepG2 cells and caused less hemolysis of G6PD-deficient red blood cells at similar concentrations. The prodrug caused less alteration in the biochemical parameters than did PQ. Histopathological analysis of the liver and kidney did show differences between the control and Phe-Ala-PQ-treated groups, but they were not statistically significant. Taken together, the results highlight the prodrug as a novel lead compound candidate for the treatment of P. vivax malaria and as a blocker of malaria transmission.

Effects of chronic stress and alendronate therapy on the osseointegration of titanium implants.

PURPOSES: The purposes of this study were to evaluate the influence of chronic stress (CS) on implant osseointegration and also to analyze whether alendronate (ALN) therapy could prevent these eventual stress-negative effects. MATERIALS AND METHODS: Adult male Holtzmann rats were assigned to one of the four experimental groups: AL (ALN; 1 mg/kg/week; n = 12), ALS (ALN + CS; 1 mg/kg/week; n = 12), CTL (sterile physiological saline; n = 12), or CTLS (sterile physiological saline + CS; n = 12). After 58 days of drug therapy, the ALS and CTLS groups were exposed to CS, and 2 days later all animals underwent tibial implant installation. The animals were euthanized 28 days following the operative surgical procedure. RESULTS: It was observed that the CTLS group presented an impairment of bone metabolism represented by lowest levels of bone-specific alkaline phosphatase and bone area fraction occupancy values. Furthermore, these animals presented a higher proportion of empty osteocytic lacunae. In contrast, the ALN therapy showed increased osseointegration and torque value parameters, regardless of stress exposition. CONCLUSIONS: Analysis of the data presented suggests that CS partially impairs the osseointegration of tibial implants and that ALN therapy is able to prevent these negative effects.

Evaluation of the host response in various models of induced periodontal disease in mice.

BACKGROUND: The aim of this study is to characterize and evaluate the host response caused by three different models of experimental periodontitis in mice. METHODS: C57BL/6 wild-type female mice were distributed into six experimental groups and sacrificed at 7, 15, and 30 days after the induction of periodontal disease: 1) group C: no treatment control group; 2) group L: periodontal disease induced by ligature; 3) group G-Pg: oral gavage with Porphyromonas gingivalis (Pg); 4) group G-PgFn: oral gavage with Fusobacterium nucleatum + Pg; 5) group I-Pg: heat-killed Pg injected into the palatal mucosa between the molars; and 6) group I-V: phosphate-buffered saline injected into the palatal mucosa. The samples were used to analyze the immune-inflammatory process in the gingival tissue via descriptive histologic and real-time polymerase chain reaction analyses. The alveolar bone loss was evaluated using microcomputed tomography. The data were analyzed using the Kruskal-Wallis test, followed by a post hoc Dunn test and analysis of variance, followed by a Tukey test using a 5% significance level. RESULTS: Only the ligature model displayed significant alveolar bone loss in the initial period (7 days), which was maintained with time. The group injected with heat-killed Pg displayed significant alveolar bone loss starting from day 15, which continued to progress with time (P <0.05). A significant increase (P <0.05) in the gene expression of proinflammatory cytokines (interleukin-6 and -1ß) and proteins involved in osteoclastogenesis (receptor activator of nuclear factor-κB ligand and osteoprotegerin) was observed in the ligature group on day 7. CONCLUSION: The ligature and injection of heat-killed Pg models were the most representative of periodontal disease in humans, whereas the oral gavage models were not effective at inducing the disease under the experimental conditions.

Seguimiento multidisciplinario en el control del penfigoide de membranas mucosas / Multidisciplinary follow-up in mucous membranes pemphigoid control

El término penfigoide de membranas mucosas designa un grupo de enfermedades vesículo-bulosas autoinmunes crónicas, que afectan predominantemente mucosas. El presente artículo describe dos casos clínicos de penfigoide de membranas mucosas con compromiso gingival y tuvo como objetivo resaltar la importancia de un correcto diagnóstico de la lesión y discutir la conducta terapéutica. Fueron realizados diversos exámenes complementares como, examen de Nikolsky, biopsia incisional, investigación de células LE y de anticuerpos antinucleares, además de la evaluación de médicos especializados en dermatología y oftalmología. Fue fundamental la substitución de dentífricos, la orientación nutricional y psicológica, el cuidado con la higiene, además del uso de corticoides tópicos. Hubo periodos de remisión y exacerbación del cuadro clínico durante el seguimiento, fue necesario el ajuste en la terapéutica y refuerzo en los cuidados con la higiene bucal. Es muy importante la interacción multidisciplinaria en la atención de estos casos para el control del tratamiento y seguimiento, además de reforzar todas las orientaciones y cuidados en lo que se refiere a la salud bucal y cautela en el uso de corticoides(AU)

The term Mucous Membrane Pemphigoid includes a group of chronic and autoimmune vesiculobullous diseases involving mainly the mucosa. The aim of present paper is to describe two clinical cases of Mucous Membrane Pemphigoid with gingival involvement to arrive to a proper diagnosis of the lesion and also to discuss the therapeutic behavior. Different complementary examinations were conducted including Nikolsky test, incisional biopsy, the LE cells study and of antinuclear antibodies, as well as the evaluation of dermatologists and ophthalmologists. It was necessary the replacement of toothpastes, the nutritional and psychological guiding, the hygiene care and the use of topic corticoids. There were periods of remission and exacerbation of clinical picture during follow-up being necessary the therapeutics fitting and the oral hygiene care reinforcement. It is important the multidisciplinary interaction in the care of these cases for treatment and follow-up control, as well as to reinforce all orientations and cares related to oral hygiene and the caution in the use of corticoids(AU)

Giant cell angiofibroma of the oral cavity: A case report and review of the literature.

Giant cell angiofibroma is a well-circumscribed, normally encapsulated, distinctive orbital soft tissue tumor. However, it is now recognized that this lesion can also present in other locations, including the oral cavity. The morphological hallmark is a richly vascularized, patternless spindle cell proliferation containing pseudovascular spaces and floret-type multinucleate giant cells. CD34 immunoreactivity, although not specific, represents the only immunohistochemical finding of potential diagnostic value. We present a case of a 44-year-old male Caucasian patient complaining of painless solitary nodule arising on the right buccal mucosa, which was diagnosed as giant cell angiofibroma. To the best of our knowledge, this is the third case of oral giant cell angiofibroma reported in the English-language literature.