Cinnamyl Schiff bases: synthesis, cytotoxic effects and antifungal activity of clinical interest.

The aim of this study was to synthesize and investigate the in vitro antifungal properties of 23 cinnamyl Schiff bases. In addition, cytotoxic effects of such cinnamyl Schiff bases against human lung, kidney or red blood cells were also checked. The compounds were synthesized in a single-step, 2 min of reaction under microwave irradiation produced up to 97% yield. Six of the 23 cinnamyl Schiff bases possessed antifungal activities against strains of Candida, Aspergillus, Fonsecaea and, particularly, Cryptococcus species. Indeed, cinnamyl Schiff bases 1 and 23 exhibited minimum inhibitory concentration (MIC) values more than twofold lower than fluconazole (FCZ) against all the Cryptococcus neoformans strains (MIC = 1·33, 1·4 and 5·2 µg ml-1 , respectively) and Cryptococcus gattii strains (MIC = 5·3, 2·8 and 9·2 µg ml-1 , respectively) (12 strains of each species) while cinnamyl Schiff base 11 was as potent as FCZ against all strains from both Cryptococcus species. No significant cytotoxic effects were observed for Schiff bases against human lung, kidney or red blood cells, all presenting selective indexes higher than 10. In conclusion, this study revealed cinnamyl Schiff bases, especially 1 and 23, as new lead anticryptococcal agents for the discovery of novel antifungal drugs. SIGNIFICANCE AND IMPACT OF THE STUDY: The occurrence and severity of fungal infections have increased in recent decades due to resistance to available antifungal drugs and the appearance of new emerging pathogens. Thus, the search for new antifungal agents is mandatory. From a series of 23 cinnamyl Schiff bases, two compounds (1 and 23) were interrogated as new anticryptococcal agents without significant cytotoxicity against human lung, kidney or red blood cells. In turns, these new Schiff bases are lead compounds for the discovery of novel antifungal drugs.

Characterization of the Th17 profile immune response in cases of human rabies transmitted by dogs and its interference in the disease pathogenesis.

The Th17 profile immune response is influenced by the presence of cytokines such as IL-1, IL-6, TGF-ß, IL-17, and IL-23. We sought to characterize the Th17 profile in CNS samples from human rabies cases transmitted by dogs and examine its possible influence on disease pathogenesis. We observed a high expression of TGF-ß, followed by IL-23, IL-17 and IL-6, and a low expression of IL-1ß and IFN-γ. Those results suggest the participation of Th17 in rabies virus neuroinfection transmitted by dogs. IL-23 probably plays a role in maintaining the Th17 profile, but it can also interfere with the establishment of the Th1 profile and viral clearance.

Infliximab in the treatment of Budd-Chiari syndrome in Behçet's disease.

Behçet's disease is a chronic autoinflammatory disorder that usually presents with recurrent oral and genital ulcers, uveitis, skin lesions and arthritis. Any organ, however, can be involved and in a subgroup of patients the large vascular lesions are the predominant feature (vasculo-Behçet disease). We report a case of a 27-yearold man with Behçet's disease who developed Budd-Chiari syndrome while on immunosuppressive therapy. Infliximab resulted in a rapid and total clinical remission. Literature data have shown that antitumor necrosis factor alpha (anti-TNF-α) agents including infliximab can suppress disease activity but there is no long-term experience on tapering and/or discontinuation of treatment under clinical remission. Our case supports the use of infliximab in vasculo-Behçet patients.

Saccharomyces boulardii Tht 500101 changes gut microbiota and ameliorates hyperglycaemia, dyslipidaemia, and liver inflammation in streptozotocin-diabetic mice.

Type 1 diabetes mellitus (T1DM) is a disorder resulting from chronic autoimmune destruction of insulin-producing pancreatic ß-cells, lack of insulin production and hyperglycaemia. The aim of this study was to evaluate the hypothesis that streptozotocin-diabetic mice treated with Saccharomyces boulardii THT 500101 strain present improvement of glucose and triglycerides metabolism, reduction of liver inflammation concomitant with a beneficial impact in the gut microbiota profile. C57BL/6 male mice were randomly assigned into three groups: Control, Diabetes, Diabetes+Probiotic, and were euthanised 8 weeks after probiotic chronic administration. Mice submitted to treatment presented reduced glycemia in comparison with the diabetic group, which was correlated with an increase in C-peptide level and in hepatic glycogen content. Fat metabolism was significantly altered in streptozotocin-induced diabetic group, and S. boulardii treatment regulated it, leading to a decrease in serum triglycerides secretion, increase in hepatic triglycerides storage and modulation of inflammatory profile. The phenotypic changes seen from chronic S. boulardii treatment were found to be broadly associated with the changes in microbioma of diabetic animals, with increased proportion in Bacteroidetes, Firmicutes and Deferribacteres, and a decreased proportion of Proteobacteria and Verrucomicrobia phylum. Thus, the data presented here show up a novel potential therapeutic role of S. boulardii for the treatment and attenuation of diabetes-induced complications.

Shear bond strength of an orthodontic self-etching adhesive after intracoronary bleaching.

OBJECTIVES: To evaluate the effects of intracoronary bleaching on the bond strength of orthodontic brackets using self-etching and total-etch adhesive systems. MATERIAL AND METHODS: In 60 bovine incisors, a coronal lingual access was made to clean the pulp chamber and standardise the thickness of the dentine. The sample was randomly divided into four groups (each n = 15): (CT), control group, without bleaching and bonded with the total-etch system (Transbond(™) XT-3M); (CTSE), without bleaching treatment and bonded with the self-etching system (Transbond(™) Plus Self-Etching Primer-3M); (BT), treated with 35% hydrogen peroxide for internal bleaching and bonded with the total-etch adhesive system; and (BTSE), treated with 35% hydrogen peroxide and bonded with the self-etching adhesive system. Shear bond strength was measured using a universal testing machine (EMIC). The adhesive remnant index (ARI) score was verified. The data were analysed using a two-way anova and Tukey test (p < 0.05). RESULTS: Significant differences were found, and the self-etching adhesive groups presented the highest bond strength values (CTSE=11.55 ± 2.85 MPa; BTSE=14.14 ± 2.23 MPa). The ARI scores revealed significant differences among the groups; the greater amount of remaining adhesive was observed in the CTSE group, and the lowest scores were observed in the BT group. CONCLUSIONS: The use of the self-etching adhesive system, even after intracoronal bleaching, presented satisfactory adhesive strength for the bonding of brackets.

P-gp modulating drugs greatly potentiate the in vitro effect of ivermectin against resistant larvae of Haemonchus placei.

Since its production in the 1980s, ivermectin (IVM) has been used indiscriminately and the selection pressure to which bovine gastrointestinal nematodes have been exposed has been intense, resulting in considerable economic losses due to parasitic resistance. One possibility for the control of resistant parasites is the use of P-glycoprotein (P-gp) modulators, because one of the main biochemical changes in ivermectin-resistant parasites is the increased activity of membrane proteins responsible for the efflux of drugs and xenobiotics. This study aimed to evaluate the in vitro effect of eight P-gp modulating drugs to potentiate IVM efficacy against an IVM-resistant field isolate of Haemonchus placei (Nematoda: Trichostrongylidae). The association of IVM with cyclosporin-A, ceftriaxone, dexamethasone, diminazene aceturate, quercetin, trifluoperazine, verapamil, or vinblastine resulted in increased IVM (10(-4)M) efficacy of 5.1%, 49.06%, 76.42%, 3.31%, 28.85%, 13.74%, 45.64% and 43.61%, respectively, and reduced the IVM half maximal effective concentration (EC50) from 4.381 × 10(-6)M to 9.877 × 10(-8), 2.739 × 10(-7), 1.240 × 10(-6), 1.651 × 10(-6), 2.710 × 10(-7), 1.159 × 10(-7), 1.026 × 10(-6) and 7.136 × 10(-7)M, respectively. Only diminazene aceturate did not significantly reduce the number of migrating larvae when associated with IVM (P > 0.05). The effect of P-gp modulating drugs depended on IVM concentration, with greater potentiating effect at lower IVM concentrations. The in vitro application of trifluoperazine, dexamethasone, quercetin, verapamil, cyclosporin A, vinblastine, and ceftriaxone potentiated IVM efficacy against an IVM-resistant field isolate of H. placei, resulting in higher efficacy and lower IVM EC50.

Identifying student profiles and their impact on academic performance in a Brazilian undergraduate student sample.

The recognition of the student profile provides strategic information for planning educational policies in the university environment. The aims of this study were to identify natural segmentation of freshman undergraduate dental students based on demographic, socioeconomic and educational variables, and to subsequently investigate their impact on academic performance of Brazilian undergraduate students. Cluster analysis (two-step algorithm) was used to segment students who entered dental school in the time period from 1999 to 2001 (n=158) into groups based on responses to a questionnaire completed by students at the time of the admission examination. Clustering analysis revealed three natural groups. Age, the parents' level of education, and performance on the first admission test were the most important variables for cluster segmentation. Cluster 1 (n=42; 26.6%) was characterized by female students with higher socioeconomic status and better previous educational indicators. Cluster 2 (n=62; 39.2%) represented disadvantaged socioeconomic profiles, with a predominance of females and older students. Cluster 3 (n=54; 34.2%) showed similar socioeconomic characteristics to cluster 1, except for male prevalence, higher age, and experiencing difficulty in the admission test. Clusters' academic performance was satisfactory in both overall course and course groups (grade point average of at least 7.0), with average ranging from 7.89 (SD=0.44) to 8.13 (SD=0.31) and 7.37 (SD=0.75) to 8.31(SD=0.26), respectively. Our findings provide encouraging evidence for the current context of equality of access to education and reveal the importance of financial support to maximize successful educational experiences of socioeconomically disadvantaged dental students.

Periodic forcing in a three-level cellular automata model for a vector-transmitted disease.

A periodically forced two-dimensional cellular automata model is used to reproduce and analyze the complex spatiotemporal patterns observed in the transmission of vector infectious diseases. The system, which comprises three population levels, is introduced to describe complex features of the dynamics of the vector-transmitted dengue epidemics, known to be very sensitive to seasonal variables. The three coupled levels represent the human, the adult, and immature vector populations. The dynamics includes external seasonality forcing, human and mosquito mobility, and vector control effects. The model parameters, even if bounded to well-defined intervals obtained from reported data, can be selected to reproduce specific epidemic outbursts. In the current study, explicit results are obtained by comparison with actual data retrieved from the time series of dengue epidemics in two cities in Brazil. The results show fluctuations that are not captured by mean-field models. It also reveals the qualitative behavior of the spatiotemporal patterns of the epidemics. In the extreme situation of the absence of external periodic drive, the model predicts a completely distinct long-time evolution. The model is robust in the sense that it is able to reproduce the time series of dengue epidemics of different cities, provided that the forcing term takes into account the local rainfall modulation. Finally, an analysis is provided of the effect of the dependence between epidemics threshold and vector control actions, both in the presence and absence of human mobility factor.

Role of Tamm-Horsfall protein in the binding and in vivo phagocytosis of type 1 fimbriated Escherichia coli by mouse peritoneal macrophages.

Tamm-Horsfall glycoprotein (THP) contains manno-oligosaccharides that are recognized by type 1 fimbriae (F1) of Escherichia coli. In the present study, we examined the in vivo phagocytic activity of mouse peritoneal macrophages after treatment of bacteria with THP. At low THP concentrations (12.5 microg/ml and 50 microg/ml) no significant difference was observed in the phagocytosis of E. coli F1+. However, at high THP concentrations (500 microg/ml and 1250 microg/ml) we obtained a reduction of bacterial phagocytosis by mouse peritoneal macrophages.

Role of Tamm-Horsfall protein in the binding and in vivo phagocytosis of type 1 fimbriated Escherichia coli by mouse peritoneal macrophages

Tamm-Horsfall glycoprotein (THP) contains manno-oligosaccharides that are recognized by type 1 fimbriae (F1) of Escherichia coli. In the present study, we examined the in vivo phagocytic activity of mouse peritoneal macrophages after treatment of bacteria with THP. At low THP concentrations (12.5 æg/ml and 50 æg/ml) no significant difference was observed in the phagocytosis of E. coli F1+. However, at high THP concentrations (500 æg/ml and 1250 æg/ml) we obtained a reduction of bacterial phagocytosis by mouse peritoneal macrophages

Monocyte and lymphocyte interaction in patients with advanced cancer. Evidence for deficient IL-1 production.

Patients with advanced neoplasms have a variety of immunologic abnormalities, including the impaired responsiveness of peripheral blood lymphocytes to mitogen and alloantigen. In the current study it was observed that cancer patients have increased monocyte suppressor cell activity that is mediated by prostaglandins and contributes to the depressed proliferative response of the patients' T-cells. This monocyte suppression, however, is not the major cause of the depressed proliferative response. The study also demonstrated that levels of interleukin 1 (IL-1) produced by lypopolysacharide-activated monocytes from cancer patients are significantly lower than they are in normal subjects.

Quantificacao de imunocomplexos circulantes atraves do PEG a 3,5%.Caracterizacao no lupus eritematoso sistemico e outras nefropatias. / Quantification of circulating immunocomplexes through the PEG 3,5%.Characterization in lupus erythematosus systemic and other renal diseases

No presente trabalho, os autores introduzem um metodo rapido de quantificacao de imunecomplexos circulantes e analisam o seu comportamento no lupus eritematoso e comparam os dados obtidos com aqueles observados em outras nefropatias