Cholesteryl Ester Transfer Protein Expression Is Down-regulated In Hyperinsulinemic Transgenic Mice.

Cholesteryl ester transfer protein (CETP) mediates cholesteryl ester (CE) and triglyceride redistribution among plasma lipoproteins. In this work, we investigated whether varying levels of insulin regulate the CETP expression in vivo. Insulin deficiency [streptozotocin (STZ) injection], and hyperinsulinemia (insulin injections, 14 days) were induced in transgenic mice expressing a human CETP minigene flanked by its natural regulatory sequences. Glucose supplementation was provided to the hyperinsulinemic group (INS+GLUC) and to an extra group of mice (GLUC). In the STZ group, endogenous CE transfer rate, plasma CETP, and hepatic CETP mRNA levels were enhanced 3.0-, 1.5-, and 2.5-fold, respectively, as compared with controls. Insulin replacement in STZ mice normalized their glycemia and liver mRNA levels. Higher plasma CETP levels were observed in GLUC mice, which were decreased in INS+GLUC mice. Hepatic CETP mRNA was not altered in GLUC mice and was reduced by one-third in INS+GLUC mice. These results show that: 1) STZ treatment increases CETP plasma levels and liver mRNA expression; 2) diet glucose supplementation increases plasma CETP levels but does not change liver mRNA abundance; and 3) daily insulin injections blunt the glucose-stimulated CETP expression by reducing its liver mRNA levels. These data suggest that insulin down-regulates CETP gene expression.441870-

Effect of essential oil obtained from Croton cajucara Benth. on gastric ulcer healing and protective factors of the gastric mucosa

The bark of Croton cajucara Benth. (Euphorbiaceae) is used widely in Amazonian folk medicine for the treatment of a wide range of gastrointestinal symptoms. Infusions of C. cajucara bark contain dehydrocrotonin (DHC), the furan diterpene, and an essential oil, a rich mixture of sesquiterpenes. Although the antiulcerogenic activity of the essential oil has been studied in different gastric ulcer models in mice and rats, its mechanism remains unclear. In this work, we examined the ability of this essential oil to increase PGE(2) release from mucus cells, as well as its effects on the amount of gastric mucus and on the healing of acetic acid-induced gastric ulcers. The essential oil (100 mg/kg body wt., p.o). significantly increased PGE(2) production by glandular cells (by 102% as compared to control) and the amount of Alcian blue binding to the gastric mucus. In chronic gastric ulcers, a single daily oral dose of essential oil (100 mg/kg body wt.) for 14 consecutive days accelerated ulcer healing to an extent similar to that seen with an equal dose of cimetidine. Thus, the protective and healing actions of the essential oil from C. cajucara bark on gastric lesions resulted mainly from an increase in PGE(2) release and gastric mucus formation which would protect the gastric mucosa.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Hypertriglyceridemia Increases Mitochondrial Resting Respiration And Susceptibility To Permeability Transition.

High plasma level of triglycerides (TGs) is a common feature in atherosclerosis, obesity, diabetes, alcoholism, stress, and infection. Since mitochondria have been implicated in cell death under a variety of metabolic disorders, we examined liver mitochondrial functions in hypertriglyceridemic transgenic mice. Hypertriglyceridemia increased resting respiration and predisposed to mitochondrial permeability transition (MPT). Ciprofibrate therapy reduced plasma TG levels, normalized respiration, and prevented MPT. The higher resting respiration in transgenic mitochondria remained in the presence of the adenine nucleotide carrier inhibitor, carboxyatractyloside, bovine serum albumin, and the uncoupling proteins (UCPs) inhibitor, GDP. UCP2 content was similar in both control and transgenic mitochondria. We propose that faster resting respiration represents a regulated adaptation to oxidize excess free fatty acid in the transgenic mice.35451-

Effects of a Mikania laevigata extract on bone resorption and RANKL expression during experimental periodontitis in rats

OBJECTIVES: The Mikania laevigata extract (MLE) (popularly known in Brazil as "guaco") possesses anti-inflammatory properties. In the present study we tested the effects of MLE in a periodontitis experimental model in rats. We also investigated possible mechanisms underlying such effects. MATERIAL AND METHODS: Periodontal disease was induced by a ligature placed around the mandibular first molars of each animal. Male Wistar rats were divided into 4 groups: non-ligated animals treated with vehicle; non-ligated animals treated with MLE (10 mg/kg, daily); ligature-induced animals treated with vehicle and ligature-induced animals treated with MLE (10 mg/kg, daily). Thirty days after the induction of periodontal disease, the animals were euthanized and mandibles and gingival tissues removed for further analysis. RESULTS: Morphometric analysis of alveolar bone loss demonstrated that MLE-treated animals presented a decreased alveolar bone loss and a lower expression of the activator of nuclear factor-κB ligand (RANKL) measured by immunohistochemistry. Moreover, gingival tissues from the MLE-treated group showed decreased neutrophil migration myeloperoxidase (MPO) assay. CONCLUSIONS: These results indicate that MLE may be useful to control bone resorption during progression of experimental periodontitis in rats