Glycerol Salicylate-based Pulp-Capping Material Containing Portland Cement.

The purpose of this study was to evaluate the water sorption, solubility, pH and ability to diffuse into dentin of a glycerol salicylate-based, pulp-capping cement in comparison to a conventional calcium hydroxide-based pulp capping material (Hydcal). An experimental cement was developed containing 60% glycerol salicylate resin, 10% methyl salicylate, 25% calcium hydroxide and 5% Portland cement. Water sorption and solubility were determined based on mass changes in the samples before and after the immersion in distilled water for 7 days. Material discs were stored in distilled water for 24 h, 7 days and 28 days, and a digital pHmeter was used to measure the pH of water. The cement's ability to diffuse into bovine dentin was assessed by Raman spectroscopy. The glycerol salicylate-based cement presented higher water sorption and lower solubility than Hydcal. The pH of water used to store the samples increased for both cements, reaching 12.59 ± 0.06 and 12.54 ± 0.05 after 7 days, for Hydcal and glycerol salicylate-based cements, respectively. Both cements were able to turn alkaline the medium at 24 h and sustain its alkalinity after 28 days. Hydcal exhibited an intense diffusion into dentin up to 40 µm deep, and the glycerol salicylate-based cement penetrated 20 µm. The experimental glycerol salicylate-based cement presents good sorption, solubility, ability to alkalize the surrounding tissues and diffusion into dentin to be used as pulp capping material.

Glycerol Salicylate-based Pulp-Capping Material Containing Portland Cement

The purpose of this study was to evaluate the water sorption, solubility, pH and ability to diffuse into dentin of a glycerol salicylate-based, pulp-capping cement in comparison to a conventional calcium hydroxide-based pulp capping material (Hydcal). An experimental cement was developed containing 60% glycerol salicylate resin, 10% methyl salicylate, 25% calcium hydroxide and 5% Portland cement. Water sorption and solubility were determined based on mass changes in the samples before and after the immersion in distilled water for 7 days. Material discs were stored in distilled water for 24 h, 7 days and 28 days, and a digital pHmeter was used to measure the pH of water. The cement's ability to diffuse into bovine dentin was assessed by Raman spectroscopy. The glycerol salicylate-based cement presented higher water sorption and lower solubility than Hydcal. The pH of water used to store the samples increased for both cements, reaching 12.59±0.06 and 12.54±0.05 after 7 days, for Hydcal and glycerol salicylate-based cements, respectively. Both cements were able to turn alkaline the medium at 24 h and sustain its alkalinity after 28 days. Hydcal exhibited an intense diffusion into dentin up to 40 µm deep, and the glycerol salicylate-based cement penetrated 20 µm. The experimental glycerol salicylate-based cement presents good sorption, solubility, ability to alkalize the surrounding tissues and diffusion into dentin to be used as pulp capping material.

O objetivo deste estudo foi avaliar a sorção e solubilidade em água, pH e habilidade de difusão na dentina de um cimento para capeamento pulpar à base de glicerol salicilato e compará-lo a um cimento comercial para capeamento pulpar à base de hidróxido de cálcio (Hydcal). Um cimento experimental contendo 60% de resina de glicerol salicilato, 10% de salicilato de metila, 25% de hidróxido de cálcio e 5% de cimento Portland foi formulado. Sorção e solubilidade em água foram determinadas a partir da alteração na massa de espécimes antes e após a imersão em água destilada por 7 dias. Discos dos cimentos foram armazenados em água destilada por 24h, 7 dias e 28 dias e o pH da água foi aferido após cada período. A habilidade de difundir-se no interior de dentina bovina foi avaliada por espectroscopia Raman. O cimento à base de glicerol salicilato apresentou maior sorção e menor solubilidade em comparação com o Hydcal. O pH da água de armazenamento dos espécimes aumentou para ambos os cimentos, chegando a 12,59±0,06 e 12,54±0,05 após 7 dias, para o Hydcal e o cimento à base de glicerol salicilato, respectivamente. Os cimentos foram capazes de promover a alcalinização do meio após 24h e sustentaram a alcalinidade após 28 dias. Hydcal exibiu intensa difusão na dentina até 40 μm de profundidade e o cimento à base de glicerol salicilato penetrou 20 μm. O cimento experimental à base de glicerol salicilato apresentou adequada sorção, solubilidade, habilidade de alcalinizar o meio e difundir-se no interior da dentina para uso como um material para capeamento pulpar.

Cocoa protective effects against abnormal fat storage and oxidative stress induced by a high-fat diet involve PPARα signalling activation.

A high-fat (HF) diet increases lipid storage and oxidative stress in mouse liver and this process seems to be mediated by Peroxisome Proliferator-Activated Receptor α (PPARα). In this study we evaluated the protective effect of cocoa against hepatic steatosis induced by a HF diet. The HF diet down-regulated PPARα expression and turned off PPARα-signalling, deregulated the ß-oxidation (ß-Ox) system and catalase (CAT) activity, increased fat storage, reduced expression of enzymatic activity involved in oxidative defence in the liver and doubled the weight gain per calorie consumed compared to animals under the normal diet. In contrast, cocoa improved hepatic ß-Ox, activated PPARα-signalling and up-regulated both gene and protein expression of SOD1. Moreover, when co-administered with the HF diet, cocoa treatment counteracted lipid storage in the liver, improved the lipid-metabolizing activity and oxidative stress defences and normalized the weight gain per calorie consumed.

Administration of ciprofibrate to lactating mothers induces PPARalpha-signaling pathway in the liver and kidney of suckling rats.

It is well known that the hypolipidemic drug ciprofibrate induces peroxisome proliferation in rodent liver, which in turn leads to the oxidative stress, and modifies some parameters related to cell proliferation and apoptosis. The administration of ciprofibrate to rats during the lactating period determined in their pups significant modifications in hepatic peroxisome enzyme activities, induction of the PPARalpha-target gene, Cyp4a10, and perturbation in cell proliferation and apoptosis, which affected the size of the liver. Moreover, this modification was associated to about two-fold induction of mRNA-PPARalpha. On the contrary, in the kidney, although a similar two-fold up-regulation of PPARalpha was detected, the induction of both peroxisomal enzyme activities and Cyp4a10 were weak, and no alterations were detected, neither in cell cycle nor in the size of the tissue. Our results indicate that the response to ciprofibrate is stronger in the liver than in the kidney of newborn rats.

Differential modulation of PPARalpha and gamma target gene expression in the liver and kidney of rats treated with aspirin.

Aspirin modified peroxisomal enzymatic activities both in the liver and renal cortex of rats, producing typical effects of peroxisomal proliferators (PPs). Although similar increments in beta-oxidation system and catalase activities were observed in both organs, induction of mRNA-Cyp4a10 and mRNA-FAT/CD36, target genes for peroxisome proliferator-activated receptors alpha (PPARalpha) and gamma (PPARgamma), respectively, was only present in the liver. There was no effect on liver mRNA-PPARalpha, while mRNA-PPARgamma was down-regulated, probably as a result of enzymatic inhibition of cyclooxygenases (COXs) by aspirin which has been shown to decrease the levels of PGJ2 and its metabolites, known as strong endogenous ligands for PPARgamma. Typical PP alterations in cell replication and apoptosis were not found during aspirin treatment or after withdrawal, suggesting that peroxisome proliferation occurs without inducing cell cycle alterations. Probably, the synergic action of both PPARalpha and PPARgamma receptors might reduce the impact on cell proliferation and apoptosis.

Plasmalogens in rat liver chromatin: new molecules involved in cell proliferation.

A minor component of chromatin, the phospholipid fraction, changes during cell cycle as result of the activation of intranuclear lipid metabolism enzymes including phosphatidylcholine-dependent phospholipase C activity. It is known that this enzyme may be activated by phosphatidylcholine plasmalogen (Plg). Until now, there has been little evidences for the presence of Plgs inside the nucleus. The aim of our study is to ascertain if they are present in the nucleus and are responsible of the activation of phosphatidylcholine-dependent phospholipase C during cell proliferation and apoptosis. Therefore, we have analysed the Plg composition of the whole homogenate, cytosol, nuclei and chromatin of hepatocytes. The phosphatidylcholine-dependent phospholipase C activity was assayed using both phosphatidylcholine and plasmalogenyl-phosphatidylcholine as substrates. Our results show, for the first time, that Plgs are present in chromatin and the plasmalogenyl-phosphatidylcholine stimulates the phosphatidylcholine-dependent phospholipase C activity more than phosphatidylcholine. Finally, in order to verify the possible role of these molecules during cell proliferation and apoptosis, we used liver of rats fed with ciprofibrate which stimulates hepatocytes proliferation during the treatment and, after withdrawal, apoptosis. After 3 days of ciprofibrate treatment, the chromatin plasmalogenyl-phosphatidylcholine increases as well as the phosphatidylcholine-dependent phospholipase C activity. After drug withdrawal, when the hepatocytes undergo to apoptosis, the plasmalogenyl-phosphatidylcholine content together with phosphatidylcholine-dependent phospholipase C activity decreases. Therefore, it can be concluded that plamalogens are present in the chromatin, and probably may have a function both in regulating phosphatidylcholine dependent phospholipase C and cell cycle.

Different effects of the liver mitogens triiodo-thyronine and ciprofibrate on the development of rat hepatocellular carcinoma.

Previous work has shown that treatment with thyroid hormone (T3) decreased the incidence of rat hepatocellular carcinoma (HCC). The present study was designed to determine whether the inhibitory effect of T3 on HCC development was limited to early steps of the carcinogenetic process or, whether a similar effect could also be exerted by starting T3 treatment at later stages. Hepatic nodules were induced in Fischer rats by a single dose of DENA, followed by a 2-week exposure of the animals to 2-AAF and partial hepatectomy. Rats were then divided into 3 groups: group 1 was maintained on basal diet: group 2 was fed a diet containing 4 mg/kg T3 for a week, every month/7 months, starting 9 weeks after DENA administration: group 3 was exposed to cycles of T3 starting 8 months after initiation. Results demonstrate that inhibition of HCC development was essentially similar in rats exposed to T3 starting either 9 weeks or 8 months after initiation (50% inhibition compared to control rats). We have previously shown that T3-induced nodule regression and HCC inhibition occurred in spite of its mitogenic effect. Therefore, we next wished to determine whether a similar antitumoral effect could be exerted by other liver mitogens, such as peroxisome proliferators. Rats exposed to the initiation-promotion protocol described previously, were subjected to 11 cycles of a T3 or a ciprofibrate-supplemented diet, each cycle consisting of 7 days/month: the incidence of HCC and lung metastases was determined 13.5 months after initiation. Results showed that although treatment with T3 strongly inhibited HCC development (only 31% of T3+ rats showed HCC vs 91% of controls), rats given ciprofibrate developed the same number of HCC as T3-untreated rats. In conclusion, the results of this study showed that the anticarcinogenic effect of T3 is maintained also when treatment begins late in the process, and its antitumoral property appears to be specific and may not be shared by other liver mitogens.