Single ulcers on the tongue dorsum: differential diagnosis between paracoccidioidomycosis and squamous cell carcinoma.

BACKGROUND: Paracoccidioidomycosis (PCM) is the leading cause of death among systemic mycoses in Brazil. On the other hand, oral squamous cell carcinoma (OSCC) is the most prevalent malignant neoplasm of the mouth. Both lesions rarely affect the tongue dorsum and may share similar clinical characteristics. This study aimed to retrieve cases of single oral ulcers diagnosed as PCM or OSCC. MATERIAL AND METHODS: A cross-sectional retrospective study was conducted. All patients who had a single ulcer on dorsum of the tongue and confirmed diagnosis of PCM or OSCC were evaluated. RESULTS: A total of 9 patients (5 women and 4 men) were evaluated, 5 patients had OSCCs (mean age = 69,8 years old), and 4 patients PCM (mean age = 51 years old). Most of the lesions were infiltrated and indurated in the palpation exam. Duration ranged from 1 to 12 months (mean time of 5.2 months and 4.7 months for OSCC and PCM, respectively). OSCC was the main clinical diagnosis hypothesis. CONCLUSIONS: Although uncommon, PCM and OSCC should be considered as a diferential diagnosis hypothesis in infiltrated ulcers on the tongue dorsum. Iincisional biopsy is mandatory to confirm the diagnosis and indicate the appropriate treatment.

High-Fidelity Controlled-Z Gate with Maximal Intermediate Leakage Operating at the Speed Limit in a Superconducting Quantum Processor.

Simple tuneup of fast two-qubit gates is essential for the scaling of quantum processors. We introduce the sudden variant (SNZ) of the net zero scheme realizing controlled-Z (CZ) gates by flux control of transmon frequency. SNZ CZ gates realized in a multitransmon processor operate at the speed limit of transverse coupling between computational and noncomputational states by maximizing intermediate leakage. Beyond speed, the key advantage of SNZ is tuneup simplicity, owing to the regular structure of conditional phase and leakage as a function of two control parameters. SNZ is compatible with scalable schemes for quantum error correction and adaptable to generalized conditional-phase gates useful in intermediate-scale applications.

4-{[4-(Hy-droxy-meth-yl)piperidin-1-yl]meth-yl}phenol.

In the title compound, C(13)H(19)NO(2), the piperidine ring has a chair conformation with the exocyclic N-C bond in an equatorial position. In the crystal, mol-ecules are linked head-to-tail by phenol O-H⋯O hydrogen bonds to hy-droxy-methyl-ene O-atom acceptors, forming chains which extend along [100]. These chains form two-dimensional networks lying parallel to (101) through cyclic hydrogen-bonding associations [graph set R(4) (4)(30)], involving hy-droxy O-H donors and piperidine N-atom acceptors.

Molecular docking studies and evaluation of the antiretroviral activity and cytotoxicity of the species Lafoensia pacari Saint-Hilaire.

Interest in antiviral plant species has grown exponentially and some have been reported to have anti-HIV properties. This research aims to perform the bio-guided phytochemical fractionation by antiretroviral activity of Lafoensia pacari stem barks. This in vitro experimental study involved the preparation of plant material, obtention of ethanolic extract, fractionation, purification, identification and quantification of fractions, acid-base extraction, nuclear magnetic resonance, HIV-1 RT inhibition test and molecular docking studies. From the bio-guided fractionation by the antiretroviral activity there was a higher activity in the acetanolic subfractions, highlighting the acetate subfraction - neutrals with 60.98% of RT inhibition and ellagic acid with 88.61% of RT inhibition and absence of cytotoxicity. The macrophage lineage cytotoxicity assay showed that the chloroform fraction was more toxic than the acetate fraction. The analysis of the J-resolved spectrum in the aromatic region showed a singlet at 7.48 and 6.93 ppm which was identified as ellagic acid and gallic acid, respectively. The 5TIQ enzyme obtained better affinity parameter with the ellagic acid ligand, which was confirmed by the HSQC-1H-13C spectra. Gallic acid was also favorable to form interaction with the 5TIQ enzyme, being confirmed through the HSQC-1H-13C spectrum. From the PreADMET evaluation it was found that ellagic acid is a promising molecule for its RT inhibition activity and pharmacokinetic and toxicity parameters.

Effects of photobiomodulation therapy on the extracellular matrix of human dental pulp cell sheets.

Photobiomodulation therapy (PBMT) and the cell sheet (CS) technology improve processes relevant to tissue regeneration. The aim of this study was to investigate the effects of different PBMT parameters on the architecture (histology), protein composition (Western blotting and immunohistochemistry) and ultrastructure [scanning electron microscopy (SEM) and transmission electron microscopy (TEM)] of the extracellular matrix (ECM) synthesized by CSs composed by human dental pulp stem cells (hDPSCs). METHODS: Thawed cells were recharacterized by the expression profile of the surface molecules of mesenchymal stem cells (MSCs) using flow cytometry. Clonogenic medium supplemented with vitamin C (20 µg/ml) was used for obtaining the CSs. PBMT was performed with continuous-wave diode laser (660 nm, 20 mW, 0.028cm2, 0.71 W/cm2) in punctual and contact mode. The CSs were allocated in 3 experimental groups: Control: no further treatment; PBMT1 [4 s, 3 J/cm2 (lower energy density), 0.08 J/point] and PBMT2 [7 s, 5 J/cm2 (higher energy density), 0.14 J/point]. Statistical comparisons were performed (p ≤ .05). RESULTS: The cells presented the classical immunoprofile of MSCs. Type I and type III collagens and fibronectin were present in the ECM of the CSs. PBMT1 induced higher amount of fibronectin. The overall ultrastructure of the CSs in the PBMT1 was epithelial-like, whereas the PBMT2 leads to CSs with fusiform cells arranged in bundles. TEM identified a more mature ECM and signs of apoptosis and necrosis in the PBMT2 group. CONCLUSION: PBMT influence the composition and ultrastructure of the ECM of CSs of hDPSCs. Thus, PBMT, specifically when applied in the lower energy density, could be of importance in the determination of the mechanical quality of CSs, which may favor cell therapy by improving the CS transplantation approach.

Screening of hydrogel-based scaffolds for dental pulp regeneration-A systematic review.

OBJECTIVE: The aim of this systematic review was to evaluate the most appropriate hydrogel scaffold type (natural, synthetic or hybrid) to be applied with stem cells for dental pulp regeneration. The findings should help clinicians make an informed choice about the appropriate scaffold to be applied for this approach. DESIGN: Three electronic databases were searched (Medline, Web of Science and Scopus). The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). RESULTS: From 4990 potentially relevant studies initially identified, 18 papers fulfilled the eligibility criteria and were considered for this review. Natural scaffolds were applied in most studies. Collagen was the most studied scaffold. In 5 of 10 studies, only growth factors were added to the constructs. Even without growth factors, these scaffolds containing stem cells were able to support the formation of dentin. The synthetic scaffolds were the least studied. Only 4 studies were selected, and in 3 of them, the same scaffold (Puramatrix) was evaluated. Puramatrix by itself was unable to form dental pulp when dental pulp stem cells were not present. Synthetic and hybrid hydrogels were unable to attract stem cells from the host. The presence of growth factors in these constructs seems to be of relevance since dental pulp tissue formation was achieved only when the hybrid scaffold was applied with growth factors. CONCLUSION: All types of hydrogel-based scaffolds, when containing mesenchymal stem cells, are able to form connective tissue with different degrees of similarity to dental pulp. However, current data is too heterogeneous to compare and identify the advantages of any specific scaffold.

Micro-computed tomography and histomorphometric analysis of human alveolar bone repair induced by laser phototherapy: a pilot study.

Immediate dental implant placement in the molar region is critical, because of the high amount of bone loss and the discrepancy between alveolar crest thickness and the implant platform. Laser phototherapy (LPT) improves bone repair. The aim of this study was to evaluate the human alveolar bone repair 40 days after molar extraction in patients submitted to LPT. Twenty patients were selected for this randomized controlled clinical trial; 10 underwent LPT (laser group) with a GaAlAs diode laser (808 nm, 100 mW, 0.04 cm(2), 75 J/cm(2), 30s per point, 3 J per point, at five points). The control group patients (n=10) were not irradiated. Forty days later, the tissue formed inside the sockets was analyzed by micro-computed tomography and histomorphometry. Data from the two groups were compared with Student's t-test and Pearson's correlation test. The relative bone volume was significantly higher in the laser group (P<0.0001). The control group showed negative correlations (P<0.01) between number and thickness, and between number and separation of trabeculae, and a positive correlation between thickness and separation of trabeculae. The laser group showed a significant negative correlation between the number and thickness of trabeculae (P<0.01). The results suggest that LPT is able to accelerate alveolar bone repair after molar extraction, leading to a more homogeneous trabecular configuration represented by thin and close trabeculae.

Modulation of B lymphocyte function by an aqueous fraction of the ethanol extract of Cissampelos sympodialis Eichl (Menispermaceae).

Cissampelos sympodialis Eichl species are used in folk medicine for the treatment of asthma, arthritis and rheumatism. In the present study, we investigated the immunomodulatory effect of an aqueous fraction of a 70% (v/v) ethanol extract of C. sympodialis leaves on B lymphocyte function. The hydroalcoholic extract inhibited the in vitro proliferative response of resting B cells induced by LPS (IC50 = 17.2 g/ml), anti-delta-dextran (IC50 = 13.9 g/ml) and anti-IgM (IC50 = 24.3 g/ml) but did not affect the anti-MHC class II antibody-stimulated proliferative response of B cell blasts obtained by stimulation with IL-4 and anti-IgM. Incubation with the hydroalcoholic extract used at 50 g/ml induced a 700% increase in intracellular cAMP levels. IgM secretion by resting B cells (obtained from normal mice) and polyclonally activated B cells (obtained from Trypanosoma cruzi-infected animals) was inhibited by the hydroalcoholic extract. The latter were more sensitive to the hydroalcoholic extract since 6.5 g/ml induced a 20% inhibition in the response of cells from normal mice while it inhibited the response of B cells from infected animals by 75%. The present data indicate that the alcoholic extract of C. sympodialis inhibited B cell function through an increase in intracellular cAMP levels. The finding that the hydroalcoholic extract inhibited immunoglobulin secretion suggests a therapeutic use for the extract from C. sympodialis in conditions associated with unregulated B cell function and enhanced immunoglobulin secretion. Finally, the inhibitory effect of the hydroalcoholic extract on B cells may indicate an anti-inflammatory effect of this extract.

Cissampelos sympodialis Eichl (Menispermaceae) leaf extract induces interleukin-10-dependent inhibition of Trypanosoma cruzi killing by macrophages.

The aqueous fraction of the ethanolic extract (AFL) of Cissampelos sympodialis Eichl (Menispermaceae), popularly known as milona, has been shown to have both immunosuppressive and anti-inflammatory effects. In the present study we investigated the modulation of macrophage antimicrobicidal activity by in vitro treatment with the extract from C. sympodialis. Normal and thioglycolate-elicited mouse peritoneal macrophages were infected in vitro with the protozoan Trypanosoma cruzi DM28c clone. We observed that the AFL (used at doses ranging from 13 to 100 microg/ml) increased T. cruzi growth and induced a 75% reduction in nitric oxide production. This inhibition could be mediated by the stimulation of macrophage interleukin-10 (IL-10) secretion since the in vitro treatment with the AFL stimulated IL-10 production by T. cruzi-infected macrophages. These results suggest that the anti-inflammatory effect of the AFL from C. sympodialis could be, at least in part, mediated by the inhibition of macrophage functions and that the inhibition of macrophage microbicidal activity induced by the C. sympodialis extract may be mediated by the decrease in macrophage function mediated by interleukin-10 production.

Studies on the anti-inflammatory and analgesic activity of Curatella americana L.

Curatella americana L. (Dilleneaceae) popularly known as 'cajueiro-bravo' and 'sambaiba' is used in Brazilian folk medicine for the treatment of inflammation and ulcer. The anti-inflammatory and analgesic tests were conducted with the hydroalcoholic extract (HAE) of the bark of the plant. The HAE inhibited mouse ear oedema induced by o-tetradecanoyl phorbol acetate (TPA) and by capsaicin. While the ID50 values obtained for the HAE against these two irritants were 40.8 +/- 1.7 and 30 +/- 1.2 mg/kg i.p. (mean +/- S.E.M., n = 6), respectively, the corresponding value for carrageenan induced paw oedema (3 h) was 21.8 +/- 2.1 mg/kg, i.p., n = 6. In the established adjuvant-induced arthritis model, the HAE significantly inhibited the oedema in daily doses of 50 mg/kg, i.p. (n = 10). The HAE also inhibited acetic acid-induced writhing (ID50 23.2 +/- 0.8 mg/kg, i.p., n = 6) and the formalin-induced late phase paw licking response (ID50 11.9 +/- 1.2 mg/kg, i.p., n = 10) in the mice. However, the HAE was inactive in the formalin-induced initial paw licking response in mice or heat induced tail flick response in rats. The HAE has shown both anti-inflammatory and peripheral analgesic activities when administrated in the mouse by the intraperitoneal route in doses which are at least 12 times lower than its LD50 dose of 647 mg/kg, i.p.

Anxiolytic-like effect of Citrus limon (L. ) Burm f. essential oil inhalation on mice / Efeito ansiolítico da inalação do óleo essencial de Citrus limon (L. ) Burm f. em camundongos.

ABSTRACT Experimental in vivo study aimed to characterize the anxiolytic-like effect of the Citrus limon fruit peel’s essential oil (CLEO) in animal models of anxiety, besides evaluating the viability J774.A1 cells in vitro through the MTT reduction method at the concentrations of 10 and 100 µg/mL. The anxiolytic behavior was evaluated in Swiss mice (n = 8) using the methodology of Elevated Plus-Maze (EPM) and Open-Field (OF). CLEO was tested by inhalation at the doses of 100, 200, and 400 µL, and as control, animals were subjected to inhalation of the vehicle (saline solution 0.9% + Tween80®) and intraperitoneal administration of diazepam (1.5 mg/kg). In the cell viability assay, it was observed that none of the concentrations showed cytotoxicity. OF test showed significant anxiolytic activity at all tested doses of OECL, compared to the control group, without changing the motor performance of the animals. Corroborating OF data, the EPM test confirmed anxiolytic activity in at least two doses of the tested oil (200 and 400 µL), justified by the number of entries and increase in the percentage of time in the open arms. The data analysis of this study evidenced that inhalation of OECL was able to induce an anxiolytic behavior in mice; however, further studies are required to ensure its safe use by the population.

RESUMO O estudo experimental in vivo objetivou caracterizar o efeito ansiolítico do óleo essencial das cascas do fruto de Citrus limon (OECL) em modelos animais de ansiedade, além de avaliar in vitro a viabilidade de células J774.A1 através do método de redução do MTT nas concentrações de 10 e 100 µg/mL. O comportamento ansiolítico foi avaliado em camundongos Swiss (n = 8), utilizando a metodologia do Labirinto em Cruz Elevado (LCE) e do Campo Aberto (CA). O OECL foi testado por inalação nas doses de 100, 200 e 400 µL, e como controle, os grupos foram submetidos à inalação do veículo (Solução fisiológica 0,9% + Tween80®) e administração intraperitoneal de diazepam (1,5 mg/kg). No ensaio de viabilidade celular, observou-se que nenhuma das concentrações apresentou citotoxicidade. O teste de CA demonstrou atividade ansiolítica significativa em todas as doses testadas do OECL, comparada ao grupo controle, sem alterar a performance motora dos animais. Corroborando os dados do CA, o teste do LCE confirmou a atividade ansiolítica em pelo menos duas das doses do óleo testadas (200 e 400 µL), justificada pelo número de entradas e aumento na percentagem de tempo nos braços abertos. A análise dos dados deste estudo evidenciou que a inalação do OECL foi capaz de induzir um comportamento ansiolítico em camundongos; entretanto, outros estudos são necessários para garantir o seu uso seguro pela população.

Avaliação da atividade antibacteriana, citotóxica e antioxidante da espécie vegetal Opuntia cochenillifera (L. ) Mill / Evaluation of antibacterial, cytotoxic, and antioxidant activity of the plant species Opuntia cochenillifera (L. ) Mill

RESUMO O presente estudo teve como objetivo avaliar a atividade antibacteriana, antioxidante e citotóxica da espécie Opuntia cochenillifera (L.) Mill. Foi realizada a prospecção fitoquímica e espectroscopia de absorção de infravermelho (IV) dos extratos etanólicos brutos e frações dos cladódios grande e pequeno. A atividade antioxidante foi avaliada pelo método da capacidade sequestradora de radicais livres utilizando o radical sintético 2,2-difenil-1-picrilhidrazila (DPPH). A atividade citotóxica foi obtida através do método colorimétrico do Metiltetrazolium (MTT). Já a atividade antibacteriana foi avaliada pelo método de microdiluição em caldo para determinar a concentração inibitória mínima (CIM) frente às estirpes bacterianas Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa e Escherichia coli. A prospecção fitoquímica revelou principalmente a presença de fenóis, esteroides livres, alcaloides, alcanos, além de outras classes químicas. O IV apresentou grupos funcionais como alcanos, carbonilas, grupos de metila, duplas ligações de carbono, grupamentos alquilamina, entre outros. Sobre a citotoxicidade na concentração de 100 μg/mL, os dois extratos brutos, todas as frações do cladódio grande e as frações de clorofórmio e metanol do cladódio pequeno não apresentaram toxicidade. Os extratos brutos e frações do cladódio grande e pequeno, não demonstraram atividade antibacteriana e nem antioxidante. Esses resultados podem fornecer suporte para pesquisas futuras, visando outras atividades biológicas da presente espécie vegetal.

ABSTRACT The purpose of this study was to evaluate the antibacterial, antioxidant, and cytotoxic activity of Opuntia cochenillifera (L.) Mill. A phytochemical screening and infrared (IR) absorption spectroscopy were performed in the crude ethanolic extracts and fractions of large and small cladodes. The antioxidant activity was evaluated through the qualitative method of free-radical scavenging capacity using the synthetic radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). The cytotoxic activity was obtained by the cell viability assay using methyl thiazolyl tetrazolium (MTT). Antibacterial activity was evaluated by broth microdilution method to determine the minimum inhibitory concentration (MIC) against the bacterial strains Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia coli. The phytochemical screening mainly revealed the presence of phenols, flavonoids, free steroids, alkaloids, alkanes, and other chemical classes. The IR spectroscopy presented functional groups such as alkanes, carbonyls, methyl groups, carbon double bonds, and alkylamino groups, among others. Regarding cytotoxicity in the concentration of 100 μg/mL, neither the crude extracts, the fractions of the large cladode, nor the chloroform and methanol fractions of small cladode presented toxicity. The crude ethanolic extracts and fractions of large and small cladode showed no antibacterial or antioxidant activity. These results may provide support for future research aimed at other biological activities of this plant species.

Increased immunoglobulin secretion by B lymphocytes from Trypanosoma cruzi infected mice after B lymphocytes-natural killer cell interaction.

In the present study, we investigated whether natural killer (NK) cells modulate immunoglobulin (Ig) secretion by B cells from Trypanosoma cruzi-infected mice. B cells from infected mice increased IgM and IgG2a secretion in the presence of a NK cell line, and this response was cell contact-dependent. Stimulation of splenic B cells with polyinosinic-polycytidylic acid, a NK cell activator, also increased Ig secretion by B cells from infected mice. B cells from infected mice expressed higher levels of the B7.2 molecule. Our results suggest that NK cells may be involved in the control of the abnormal B cell activation observed during T. cruzi infection.

Modulation of B lymphocyte function by an aqueous fraction of the ethanol extract of Cissampelos sympodialis Eichl (Menispermaceae)

Cissampelos sympodialis Eichl species are used in folk medicine for the treatment of asthma, arthritis and rheumatism. In the present study, we investigated the immunomodulatory effect of an aqueous fraction of a 70 percent (v/v) ethanol extract of C. sympodialis leaves on B lymphocyte function. The hydroalcoholic extract inhibited the in vitro proliferative response of resting B cells induced by LPS (IC50 = 17.2 æg/ml), anti-delta-dextran (IC50 = 13.9 æg/ml) and anti-IgM (IC50 = 24.3 æg/ml) but did not affect the anti-MHC class II antibody-stimulated proliferative response of B cell blasts obtained by stimulation with IL-4 and anti-IgM. Incubation with the hydroalcoholic extract used at 50 æg/ml induced a 700 percent increase in intracellular cAMP levels. IgM secretion by resting B cells (obtained from normal mice) and polyclonally activated B cells (obtained from Trypanosoma cruzi-infected animals) was inhibited by the hydroalcoholic extract. The latter were more sensitive to the hydroalcoholic extract since 6.5 æg/ml induced a 20 percent inhibition in the response of cells from normal mice while it inhibited the response of B cells from infected animals by 75 percent. The present data indicate that the alcoholic extract of C. sympodialis inhibited B cell function through an increase in intracellular cAMP levels. The finding that the hydroalcoholic extract inhibited immunoglobulin secretion suggests a therapeutic use for the extract from C. sympodialis in conditions associated with unregulated B cell function and enhanced immunoglobulin secretion. Finally, the inhibitory effect of the hydroalcoholic extract on B cells may indicate an anti-inflammatory effect of this extract.

Cissampelos sympodialis Eichl (Menispermaceae) leaf extract induces interleukin-10-dependent inhibition of Trypanosoma cruzi killing by macrophages

The aqueous fraction of the ethanolic extract (AFL) of Cissampelos sympodialis Eichl (Menispermaceae), popularly known as milona, has been shown to have both immunosuppressive and anti-inflammatory effects. In the present study we investigated the modulation of macrophage antimicrobicidal activity by in vitro treatment with the extract from C. sympodialis. Normal and thioglycolate-elicited mouse peritoneal macrophages were infected in vitro with the protozoan Trypanosoma cruzi DM28c clone. We observed that the AFL (used at doses ranging from 13 to 100 æg/ml) increased T. cruzi growth and induced a 75 percent reduction in nitric oxide production. This inhibition could be mediated by the stimulation of macrophage interleukin-10 (IL-10) secretion since the in vitro treatment with the AFL stimulated IL-10 production by T. cruzi-infected macrophages. These results suggest that the anti-inflammatory effect of the AFL from C. sympodialis could be, at least in part, mediated by the inhibition of macrophage functions and that the inhibition of macrophage microbicidal activity induced by the C. sympodialis extract may be mediated by the decrease in macrophage function mediated by interleukin-10 production

A violencia dos grandes centros urbanos. / Violence of the large urban centers

Os aspectos geneticos, neurofisiologicos, psicologicos e sociologicos da agressividade sao enfocados. Traca-se um pararelo entre a violencia e a nao-observancia da territorialidade, o ressentimento social e a desorganizacao social nas grandes cidades

O problema do dilema psiquiatrico dos delirios. Proposta de uma nova abordagem etiopatogenetica. / The problem of the psychiatric dilemma of delirium. Proposal of a new ethiopathogenetic approach

O autor propoe um novo enfoque para a problematica etiopatogenetica dos delirios.Para tanto, tenta elaborar uma concepcao onde o delirio, como fenomeno peculiar ao ser humano, seja visto e avaliado de uma forma unitaria, sem divisoes observadas entre as tendencias doutrinadas isoladas e dogmaticas, das postulacoes ate agora propostas. Desta forma, pretende compreender o sintoma, abrangendo nao somente o universo humano no momento da eclosao do delirio, e posterior desenvolvimento, como tambem todos os fatores causais, internos e externos, que historicamente contribuiram para o seu aparecimento. Tal postura tenta acrescentar, as formulacoes teoricas ja existentes, uma proposta que visa entender a unidade estrutural e formal, nao somente do delirio, mas, tambem, do homem delirante