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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 (Pâ=â0.2946). In the female gender, the age showed a low positive correlation with the L & Z classification (rhoâ=â0.398; Pâ=â0.006) and in the male gender, a moderate negative correlation was observed (rhoâ=â-0.650, Pâ=â0.016). 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.
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Implantação Dentária Endóssea , Implantes Dentários , Idoso , Densidade Óssea , Feminino , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Maxila/diagnóstico por imagem , Maxila/cirurgia , Radiografia PanorâmicaRESUMO
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.
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Neoplasias Bucais , Doenças Periodontais , Periodontite , Estudos de Casos e Controles , Estudos Transversais , Humanos , Neoplasias Bucais/complicações , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/epidemiologia , Doenças Periodontais/complicações , Doenças Periodontais/diagnóstico , Doenças Periodontais/epidemiologia , Periodontite/complicações , Periodontite/diagnóstico , Periodontite/epidemiologiaRESUMO
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.
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Proteínas 14-3-3/genética , Proteínas Fúngicas/genética , Paracoccidioides/genética , Paracoccidioides/patogenicidade , Fatores de Virulência/genética , Células Epiteliais Alveolares/microbiologia , Células Epiteliais Alveolares/patologia , Animais , Apoptose/genética , Modelos Animais de Doenças , Expressão Gênica , Pulmão/citologia , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Paracoccidioidomicose/microbiologiaRESUMO
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.
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Sporothrix/imunologia , Esporotricose/imunologia , Animais , Contagem de Colônia Microbiana , Ciclofosfamida/administração & dosagem , Citocinas/metabolismo , Modelos Animais de Doenças , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Linfonodos/imunologia , Linfonodos/microbiologia , Linfonodos/patologia , Subpopulações de Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Baço/imunologia , Baço/microbiologia , Baço/patologia , Esporotricose/microbiologia , Esporotricose/patologiaRESUMO
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.
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Inflamassomos/imunologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sporothrix/imunologia , Esporotricose/imunologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/deficiência , Sporothrix/citologia , Esporotricose/microbiologiaRESUMO
Colorectal cancer (CRC) is one of the top 10 most common cancers worldwide and caused approximately 10 million deaths in 2022. CRC mortality has increased by 10% since 2020 and 52.000 deaths will occur in 2024, highlighting the limitations of current treatments due to ineffectiveness, toxicity, or non-adherence. The widely used chemotherapeutic agent, 5-fluorouracil (5-FU), is associated with several adverse effects, including renal, cardiac, and hepatic toxicity; mucositis; and resistance. Taurine (TAU), an essential ß-amino acid with potent antioxidant, antimutagenic, and anti-inflammatory properties, has demonstrated protective effects against tissue toxicity from chemotherapeutic agents like doxorubicin and cisplatin. Taurine deficiency is linked to aging and cancers such as breast and colon cancer. This study hypothesized that TAU may mitigate the adverse effects of 5-fluorouracil (5-FU). Carcinogenesis was chemically induced in rats using 1,2-dimethylhydrazine (DMH). Following five months of cancer progression, taurine (100 mg/kg) was administered orally for 8 days, and colon tissues were analyzed. The results showed 80% of adenocarcinoma (AC) in DMH-induced control animals. Notably, the efficacy of 5-FU showed 70% AC and TAU 50% while, in the 5-FU + TAU group, no adenocarcinoma was observed. No differences were observed in the inflammatory infiltrate or the expression of genes such as K-ras, p53, and Ki-67 among the cancer-induced groups whereas APC/ß-catenin expression was increased in the 5FU + TAU-treated group. The mitotic index and dysplasia were increased in the induced 5-FU group and when associated with TAU, the levels returned to normal. These data suggest that 5-FU exhibits a synergic anticancer effect when combined with taurine.
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Neoplasias do Colo , Sinergismo Farmacológico , Fluoruracila , Taurina , Taurina/farmacologia , Animais , Fluoruracila/farmacologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Ratos , Masculino , Modelos Animais de Doenças , Adenocarcinoma/tratamento farmacológico , 1,2-Dimetilidrazina , Ratos Wistar , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologiaRESUMO
INTRODUCTION: Furoxan and benzofuroxan are compounds containing an N-oxide function, known for their diverse pharmacological properties, including antimicrobial and antiinflammatory effects. This study aimed to investigate these activities using an in-house library of N-oxide compounds. METHOD: Twenty compounds were tested against both Gram-positive and Gram-negative bacteria, including Cutibacterium acnes (C. acnes), a microorganism implicated in the development of acne vulgaris. One compound, (E)-4-(3-((2-(3-hydroxybenzoyl)hydrazone)methyl)phenoxy)-3- (phenylsulfonyl)-1,2,5-oxadiazol-2-N-oxide (compound 15), exhibited selective antimicrobial activity against C. acnes, with a Minimum Inhibitory Concentration (MIC) value of 2 µg/mL. Indirect measurement of Nitric Oxide (NO) release showed that compound 15 and isosorbide dinitrate, when treated with L-cysteine, produced nitrite levels of 20.1% and 9.95%, respectively. Using a NO scavenger (PTIO) in combination with compound 15 in a culture of C. acnes resulted in reduced antimicrobial activity, indicating that NO release is part of its mechanism of action. Cytotoxicity assessments using murine macrophages showed cellular viability above 70% at concentrations up to 0.78 µg/mL. RESULTS: Measurements of Interleukin-1 beta (IL1-ß) and Tumor Necrosis Factor-alpha (TNF-α) indicated that compound 15 did not reduce the levels of these pro-inflammatory cytokines. Sustained NO production by inducible Nitric Oxide Synthase (iNOS) in macrophages or neutrophils has been found to be involved in the inflammatory process in acne vulgaris and lead to toxicity in surrounding tissues. Nitrite levels in the supernatant of murine macrophages were found to be decreased at a concentration of 0.78 µg/mL of compound 15, indicating an anti-inflammatory effect. In vivo studies were conducted using Balb/c nude mice inoculated subcutaneously with C. acnes. Cream and gel formulations of compound 15 were applied to treat the animals, along with commercially available anti-acne drugs, for 14 days. Animals treated with a cream base containing 5% of compound 15 exhibited less acanthosis with mild inflammatory infiltration compared to other groups, highlighting its anti-inflammatory properties. CONCLUSION: Similar results were observed in the benzoyl peroxide group, demonstrating that compound 15 presented comparable anti-inflammatory activity to the FDA-approved drug. These promising results suggest that compound 15 has a dual mechanism of action, with selective antimicrobial activity against C. acnes and notable anti-inflammatory properties, making it a potential prototype for developing new treatments for acne vulgaris.
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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.
Assuntos
Carcinoma de Células Escamosas , Carcinoma de Células Escamosas/patologia , Humanos , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , LínguaRESUMO
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.
Assuntos
Lesões Pré-Cancerosas , Terpenos , Neoplasias da Língua , 4-Nitroquinolina-1-Óxido/toxicidade , Alanina Transaminase , Fosfatase Alcalina , Animais , Aspartato Aminotransferases , Creatinina , Humanos , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/patologia , Ratos , Ratos Sprague-Dawley , Terpenos/farmacologia , Língua/patologia , Neoplasias da Língua/induzido quimicamente , Neoplasias da Língua/patologia , Ureia/farmacologiaRESUMO
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.
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Cetoprofeno , Paullinia , Animais , Feminino , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , TeobrominaRESUMO
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.
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Sporothrix , Esporotricose/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Animais , Fatores de Transcrição Forkhead/imunologia , Masculino , Camundongos Endogâmicos C57BL , Baço/citologiaRESUMO
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.
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Comunicação Celular , Interações Hospedeiro-Patógeno , Paracoccidioides/patogenicidade , Paracoccidioidomicose/microbiologia , Fator Tu de Elongação de Peptídeos/metabolismo , Fatores de Virulência/metabolismo , Virulência , Animais , Regulação para Baixo , Macrófagos/imunologia , Macrófagos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Paracoccidioides/metabolismo , Paracoccidioidomicose/metabolismo , FagocitoseRESUMO
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.
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Angiofibroma/patologia , Neoplasias Bucais/patologia , Adulto , Humanos , Imuno-Histoquímica , MasculinoRESUMO
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.
Assuntos
Adjuvantes Imunológicos , Hidróxido de Alumínio/imunologia , Vacinas Fúngicas/efeitos adversos , Vacinas Fúngicas/imunologia , Sporothrix/imunologia , Esporotricose/prevenção & controle , Adjuvantes Imunológicos/toxicidade , Hidróxido de Alumínio/toxicidade , Animais , Anticorpos Antifúngicos/biossíntese , Anticorpos Antifúngicos/sangue , Anticorpos Antifúngicos/imunologia , Brasil , Vacinas Fúngicas/administração & dosagem , Vacinas Fúngicas/química , Imunidade Celular , Imunogenicidade da Vacina , Interleucina-17/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Fagocitose , Esporotricose/imunologia , Equilíbrio Th1-Th2 , VacinaçãoRESUMO
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.
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Antiprotozoários/uso terapêutico , Benzoxazóis/uso terapêutico , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Anfotericina B/toxicidade , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Benzoxazóis/química , Benzoxazóis/farmacologia , Benzoxazóis/toxicidade , Biomarcadores/metabolismo , Cricetinae , Rim/efeitos dos fármacos , Rim/parasitologia , Rim/patologia , Rim/fisiopatologia , Leishmaniose Visceral/parasitologia , Fígado/efeitos dos fármacos , Fígado/parasitologia , Fígado/patologia , Fígado/fisiopatologia , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Macrófagos/patologia , Masculino , Camundongos , Óxido Nítrico/biossíntese , Baço/efeitos dos fármacos , Baço/parasitologia , Baço/patologia , Resultado do TratamentoRESUMO
The X-linked hypophosphatemic rickets is a rare metabolic disorder characterized by low serum phosphate levels caused by a decreased renal tubular reabsorption of inorganic phosphates. The initial complaints are a delay in the development of walking caused by deformity of the legs. Oral findings include poorly mineralized dentin, enlarged pulp chambers and root canals, and periradicular abscesses in caries-free teeth. We present three patients from the same family with X-linked hypophosphatemic rickets showing bone and dental alterations.
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Hipofosfatemia Familiar/complicações , Anormalidades Dentárias/etiologia , Adulto , Criança , Necrose da Polpa Dentária/etiologia , Necrose da Polpa Dentária/terapia , Prótese Total , Feminino , Humanos , Masculino , Abscesso Periapical/etiologia , Tratamento do Canal Radicular , Anormalidades Dentárias/terapiaRESUMO
Tooth germ development is associated with morphological and biochemical changes of the dental papilla and enamel organ. Enzymes with gelatinolytic activities were studied by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzymography in tooth germ of newborn to 15-day-old rats. Three major bands with gelatinolytic activity were detected at all periods and characterized as the latent and active forms of MMP-2 using their molecular weight and activity dependent on Zn++ and Ca++ ions as criteria. Expression and activity of MMP-2 increased progressively from 0 to 15 days after birth. Mechanical separation of the tooth germ from 10-day-old rats showed that the gelatinolytic activity was localized mainly in the dental papilla and not the dental organ. These data indicate that the expression and activity of MMP-2 varies during the development and maturation of rat first molar tooth germ.
Assuntos
Metaloproteinase 2 da Matriz/metabolismo , Dente Molar/enzimologia , Germe de Dente/enzimologia , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Inibidores de Cisteína Proteinase/farmacologia , Densitometria , Papila Dentária/enzimologia , Eletroforese em Gel de Poliacrilamida , Órgão do Esmalte/enzimologia , Regulação Enzimológica da Expressão Gênica , Metaloproteinase 2 da Matriz/genética , Inibidores de Metaloproteinases de Matriz , Peso Molecular , Odontogênese/genética , Odontogênese/fisiologia , Fenantrolinas/farmacologia , Inibidores de Proteases/farmacologia , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Inibidores de Serina Proteinase/farmacologia , Zinco/metabolismoRESUMO
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.
Assuntos
Implantes Dentários , Osseointegração , Estresse Psicológico , Titânio , Animais , Doença Crônica , Corticosterona/sangue , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
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.