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)

Amplification of neuromuscular transmission by methylprednisolone involves activation of presynaptic facilitatory adenosine A(2A) receptors and redistribution of synaptic vesicles

The mechanisms underlying improvement of neuromuscular transmission deficits by glucocorticoids are still a matter of debate despite these compounds have been used for decades in the treatment of autoimmune myasthenic syndromes. Besides their immunosuppressive action, corticosteroids may directly facilitate transmitter release during high-frequency motor nerve activity. This effect coincides with the predominant adenosine A(2A) receptor tonus, which coordinates the interplay with other receptors (e.g. muscarinic) on motor nerve endings to sustain acetylcholine (ACh) release that is required to overcome tetanic neuromuscular depression in myasthenics. Using myographic recordings, measurements of evoked [H-3]ACh release and real-time video microscopy with the FM4-64 fluorescent dye, results show that tonic activation of facilitatory A(2A) receptors by endogenous adenosine accumulated during 50 Hz bursts delivered to the rat phrenic nerve is essential for methylprednisolone (03 mM)-induced transmitter release facilitation, because its effect was prevented by the A(2A) receptor antagonist, ZM 241385 (10 nM). Concurrent activation of the positive feedback loop operated by pirenzepine-sensitive muscarinic M-1 autoreceptors may also play a role, whereas the corticosteroid action is restrained by the activation of co-expressed inhibitory M-2 and Al receptors blocked by methoctramine (0.1 mu M) and DPCPX (2.5 nM), respectively. Inhibition of FM4-64 loading (endocytosis) by methylprednisolone following a brief tetanic stimulus (50 Hz for 5 s) suggests that it may negatively modulate synaptic vesicle turnover, thus increasing the release probability of newly recycled vesicles. Interestingly, bulk endocytosis was rehabilitated when methylprednisolone was co-applied with ZM241385. Data suggest that amplification of neuromuscular transmission by methylprednisolone may involve activation of presynaptic facilitatory adenosine A(2A) receptors by endogenous adenosine leading to synaptic vesicle redistribution. (C) 2014 Elsevier Ltd. All rights reserved.

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.

Inhibition of diethylnitrosamine-initiated alcohol-promoted hepatic inflammation and precancerous lesions by flavonoid luteolin is associated with increased sirtuin 1 activity in mice

Chronic and excessive alcohol consumption is an established risk for hepatic inflammation and carcinogenesis. Luteolin is one of the most common flavonoids present in plants and has potential beneficial effects against cancer. In this study, we examined the effect and potential mechanisms of luteolin supplementation in a carcinogen initiated alcohol-promoted pre-neoplastic liver lesion mouse model. C57BL/6 mice were injected with diethylnitrosamine (DEN) [i.p. 25 mg/kg of body weight (BW)] at 14 days of age. At 8 weeks of age mice were group pair-fed with Lieber-DeCarli liquid control diet or alcoholic diet [ethanol (EtOH) diet, 27% total energy from ethanol] and supplemented with a dose of 30 mg luteolin/kg BW per day for 21 days. DEN-injected mice fed EtOH diet displayed a significant induction of pre-neoplastic lesions, a marker associated with presence of steatosis and inflammation. Dietary luteolin significantly reduced the severity and incidence of hepatic inflammatory foci and steatosis in DEN-injected mice fed EtOH diet, as well the presence of preneoplastic lesions. There was no difference on hepatic protein levels of sirtuin 1 (SIRT1) among all groups; however, luteolin supplementation significantly reversed alcohol-reduced SIRT1 activity assessed by the ratio of acetylated and total forkhead box protein O1 (FoXO1) and SIRT1 target proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α). Dietary intake of luteolin prevents alcohol promoted pre-neoplastic lesions, potentially mediated by SIRT1 signaling pathway.

Participation of α2 -adrenoceptors in sodium appetite inhibition during sickness behaviour following administration of lipopolysaccharide

Sickness behaviour, a syndrome characterized by a general reduction in animal activity, is part of the active-phase response to fight infection. Lipopolysaccharide (LPS), an effective endotoxin to model sickness behaviour, reduces thirst and sodium excretion, and increases neurohypophysial secretion. Here we review the effects of LPS on thirst and sodium appetite. Altered renal function and hydromineral fluid intake in response to LPS occur in the context of behavioural reorganization, which manifests itself as part of the syndrome. Recent data show that, in addition to its classical effect on thirst, non-septic doses of LPS injected intraperitoneally produce a preferential inhibition of intracellular thirst versus extracellular thirst. Moreover, LPS also reduced hypertonic NaCl intake in sodium-depleted rats that entered a sodium appetite test. Antagonism of α2 -adrenoceptors abolished the effect of LPS on sodium appetite. LPS and cytokine transduction potentially recruit brain noradrenaline and α2 -adrenoceptors to control sodium appetite and sickness behaviour.

Structural basis for the inhibition of a phospholipase A2-like toxin by caffeic and aristolochic acids

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

Role of TRPV1 channels of the dorsal periaqueductal gray in the modulation of nociception and open elevated plus maze-induced antinociception in mice

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Dental care for cerebral palsy patients using auxiliary resources to inhibit pathological tonic reflexes

Cerebral paralysis is a chronic illness that affects the central nervous system. In this article the author describes the techniques used at CAOE (Odontological Center for Assistance to patients with special needs) to restraint CP patients during dental treatment, because they present some pathological reflexes which interfere in their odontological assistance. Also it shows how to perform a special physical restraint and how to keep the mouth open by using simple tools including a homemade one. All the devices used during the dental treatment in cerebral palsy patients, such as the physical restraint with bands or sheet to wrap them up, cylindrical pad or cushion made of a soft material, or simple tools including a homemade one to keep the mouth open are usually and safely used in CAOE. All these simple devices are necessary, because there are no available funds for the acquisition of expensive material or equipment. Despite of a shortage of resources we can easily and efficiently assist these patients.