Theoretical insight into the mechanism for the inhibition of the cysteine protease cathepsin B by 1,2,4-thiadiazole derivatives

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Inhibition of Lysozyme by Taurine Dibromamine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Angiotensin II AT(1) receptor mutants expressed in CHO cells caused morphological change and inhibition of cell growth

To assess the importance of the leucine residues in positions 262 and 265 of the angiotensin AT, receptor for signaling pathways and receptor expression and regulation, we compared the properties of CHO cells transfected with the wild type or the L262D or L265D receptor point mutants. It was found that the two mutants significantly increased the basal intracellular cyclic AMP (cAMP) formation in an agonist-independent mode. The morphology transformation of CHO cells was correlated with the increased cAMP formation, since forskolin, a direct activator of adenylate cyclase mimicked this effect on WT-expressing CHO cells. DNA synthesis was found to be inhibited in these cell lines, indicating that cAMP may also have determined the inhibitory effect on cell growth, in addition to the cell transformation from a tumorigenic to a non-tumorigenic phenotype. However a role for an increased Ca2(+) influx induced by the mutants in non-stimulated cells cannot be ruled out since this ion also was shown to cause transformed cells to regain the morphology and growth regulation. (c) 2005 Elsevier B.V. All rights reserved.

Fluoride release and secondary caries inhibition by adhesive systems on root dentine

This study tested the fluoride-release rate and the root caries inhibitory effect of dental adhesives. In phase 1, the fluoride released from samples (n = 5) of the adhesives A (Optibond Solo), B (One-up Bond F), C (Prime & Bond NT), D (Tenure Quick), and also of the controls [+] (glass-ionomer cement) and [-] (non-fluoride releasing adhesive), was quantified on a daily basis during a pH-cycling, caries-simulating phenomenon. In phase 2, restorations were made in bovine root dentine slabs (n = 16) with the same adhesives associated with a non-fluoridated composite. Control [+] restorations were made entirely with glass-ionomer cement. Specimens were thermocycled and submitted to the pH-cycling regimen. Demineralization areas and the presence of the wall lesion (WL) and the inhibition zone (IZ) were determined by polarizing light microscopy in dentine adjacent to the restoration. The highest concentration of fluoride was released by the control [+]; adhesives A, B and C, also released fluoride. No detectable amount of fluoride was released by D or [-]. Smaller areas of demineralization were found with control [+], whereas the demineralization areas of adhesives A-D and [-] did not differ from each other. No WL was detected, and higher percentages of IZ were recorded to [+] and to adhesive A. Although some dental adhesives were able to release fluoride, they could not inhibit secondary caries development as well as the glass-ionomer cement.

Caries progression and inhibition in human and bovine root dentine in situ

Since the use of bovine instead of human dentine to evaluate cariogenic and anticariogenic substances is not well established, this in situ study was conducted. Eleven volunteers wore palatal acrylic devices containing 4 dentine slabs (2 human and 2 bovine). Sucrose solution (20%) was dripped over all slabs 4 times a day, simulating a cariogenic challenge. Dentifrice slurries, fluoridated or not, were dripped over specified dentine slabs 3 times a day to evaluate caries reduction. After 14 days, the biofilm formed on the dentine slabs was collected for microbiological analysis. In dentine, mineral loss (DeltaZ) and lesion depth (LD) were determined by cross-sectional microhardness and by polarized light microscopy, respectively. The total streptococci and mutans streptococci counts in the biofilm formed either on human or on bovine slabs, whether treated or not with fluoride dentifrice, were not statistically different. The DeltaZ and the LID values of dentine treated with fluoride dentifrice were significantly lower than the values of dentine treated with non-fluoride dentifrice. The differences in the DeltaZ and LD values between the human and bovine dentine were not statistically significant. The results suggest that bovine dentine can be used instead of human to evaluate caries development and inhibition. Copyright (C) 2003 S. Karger AG, Basel.

Inhibition of bladder cancer cell proliferation by allyl isothiocyanate (mustard essential oil)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of oil overlay on inhibition potential of roscovitine in sheep cumulus-oocyte complexes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Metalloproteinase inhibition protects against reductions in circulating adrenomedullin during lead-induced acute hypertension

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of canonical siRNA and dicer substrate RNA for inhibition of hepatitis C virus genome replication: a comparative study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alterations in the water intake caused by central inhibition of angiotensin-converting enzyme in the rat

In the present study we investigated the effects of central (i.c.v.) and subcutaneous (s.c.) injections of a 2 μg dose of lisinopryl, an inhibitor of angiotensin I(ANGI)-converting enzyme (CE), on water intake. I.c.v. but not s.c. injection of lisinopryl abolished drinking in response to s.c. isoprenaline (100 μg/kg) and significantly reduced drinking in response to 24 h water deprivation or s.c. polyethylene glycol (30% w/v, 10 ml/kg). Lisinopryl had no effect on water intake induced by cellular dehydration (s.c. injection of hypertonic saline (2 M NaCl)). These results are consistent with the hypothesis that lisinopryl acts as a CE blocking agent in the brain. The thirst challenge induced by hypotension using isoprenaline acts primarily by generating ANGII systemically and centrally. The other thirst challenges such as cellular dehydration are independent of the ANGII in the brain. This conclusion was made possible by utilizing a new CE blocking agent at a smaller dose than normally used for other ANG I-CE inhibitors. © 1992.

The importance of myeloperoxidase in apocynin-mediated NADPH oxidase inhibition

Apocynin is widely used as an inhibitor of the NADPH oxidase. Since myeloperoxidase (MPO) has been considered as essential for the mechanism of action of apocynin, here we used cells with different levels of MPO and compared their sensitivity to apocynin. HL-60 cells were differentiated with DMSO or IFN γ /TNF α and compared with peripheral mononuclear (PBMC) and polymorphonuclear cells (PMN). The relative MPO activity was PBMC = HL60 DMSO < HL60 IFN γ < PMN. Apocynin inhibited the intracellular reactive oxygen species production by PMN (80%) and IFN γ /TNF α -differentiated HL-60 cells (45%) but showed a minor effect in PBMC and DMSO differentiated HL-60 cells (20%). The addition of azide decreased the efficiency of apocynin in PMN and the addition of peroxidase increased the inhibition in PBMC. We also determined the gene expression of the components gp91phox, p47phox, p22phox and p67phox in the resting cells. Apocynin did not change gp91phox, p47phox or p22phox gene expression in nonstimulated PBMC, HL60 DMSO, HL60 IFN γ /TNF α , and PMN and has a subtle increase in p67phox in HL60 IFN γ /TNF α . The results from this work suggest that a rational search for better inhibitors of NADPH oxidase in leukocytes should include a correlation with their affinity as substrates for MPO.

Anthocyanin incorporated dental copolymer: bacterial growth inhibition, mechanical properties, and compound release rates and stability by (1)h NMR

Objective. To evaluate bacterial growth inhibition, mechanical properties, and compound release rate and stability of copolymers incorporated with anthocyanin (ACY; Vaccinium macrocarpon). Methods. Resin samples were prepared (Bis-GMA/TEGDMA at 70/30 mol%) and incorporated with 2 w/w% of either ACY or chlorhexidine (CHX), except for the control group. Samples were individually immersed in a bacterial culture (Streptococcus mutans) for 24 h. Cell viability (n = 3) was assessed by counting the number of colony forming units on replica agar plates. Flexural strength (FS) and elastic modulus (E) were tested on a universal testing machine (n = 8). Compound release and chemical stability were evaluated by UV spectrophotometry and (1)H NMR (n = 3). Data were analyzed by one-way ANOVA and Tukey's test ( α = 0.05). Results. Both compounds inhibited S. mutans growth, with CHX being most effective (P < 0.05). Control resin had the lowest FS and E values, followed by ACY and CHX, with statistical difference between control and CHX groups for both mechanical properties (P < 0.05). The 24 h compound release rates were ACY: 1.33 μg/mL and CHX: 1.92 μg/mL. (1)H NMR spectra suggests that both compounds remained stable after being released in water. Conclusion. The present findings indicate that anthocyanins might be used as a natural antibacterial agent in resin based materials.