Attenuation of prostaglandin E2 elimination across the mouse blood-brain barrier in lipopolysaccharide-induced inflammation and additive inhibitory effect of cefmetazole

<p>Abstract</p> <p>Background</p> <p>Peripheral administration of lipopolysaccharide (LPS) induces inflammation and increases cerebral prostaglandin E₂(PGE₂) concentration. PGE₂is eliminated from brain across the blood-brain barrier (BBB) in mice, and this process is inhibited by intracerebral or intravenous pre-administration of anti-inflammatory drugs and antibiotics such as cefmetazole and cefazolin that inhibit multidrug resistance-associated protein 4 (Mrp4/Abcc4)-mediated PGE₂transport. The purpose of this study was to examine the effect of LPS-induced inflammation on PGE₂elimination from brain, and whether antibiotics further inhibit PGE₂elimination in LPS-treated mice.</p> <p>Methods</p> <p>[³H]PGE₂elimination across the BBB of intraperitoneally LPS-treated mice was assessed by the brain efflux index (BEI) method. Transporter protein amounts in brain capillaries were quantified by liquid chromatography-tandem mass spectrometry.</p> <p>Results</p> <p>The apparent elimination rate of [³H]PGE₂from brain was lower by 87%, in LPS-treated mice compared with saline-treated mice. The Mrp4 protein amount was unchanged in brain capillaries of LPS-treated mice compared with saline-treated mice, while the protein amounts of organic anion transporter 3 (Oat3/Slc22a8) and organic anion transporting polypeptide 1a4 (Oatp1a4/Slco1a4) were decreased by 26% and 39%, respectively. Either intracerebral or intravenous pre-administration of cefmetazole further inhibited PGE₂elimination in LPS-treated mice. However, intracerebral or intravenous pre-administration of cefazolin had little effect on PGE₂elimination in LPS-treated mice, or in LPS-untreated mice given Oat3 and Oatp1a4 inhibitors. These results indicate that peripheral administration of cefmetazole inhibits PGE₂elimination across the BBB in LPS-treated mice.</p> <p>Conclusion</p> <p>PGE₂elimination across the BBB is attenuated in an LPS-induced mouse model of inflammation. Peripheral administration of cefmetazole further inhibits PGE₂elimination in LPS-treated mice.</p

Wnt5 is required for notochord cell intercalation in the ascidian Halocynthia roretzi

Background information. In the embryos of various animals, the body elongates after gastrulation by morphogenetic movements involving convergent extension. The Wnt/PCP (planar cell polarity) pathway plays roles in this process, particularly mediolateral polarization and intercalation of the embryonic cells. In ascidians, several factors in this pathway, including Wnt5, have been identified and found to be involved in the intercalation process of notochord cells

Identification of a phosphorylation site of the rat insulin receptor catalyzed by protein kinase C in an intact cell

AbstractIn two-dimensional tryptic phosphopeptide mapping, the β-subunit of the insulin receptor phosphorylated by 12-O-tetra-decanoylphorbol-13-acetate in rat hepatoma cells (H-35) was separated into one phosphothreonine-containing peptide and several phosphoserine-containing peptides. The synthetic peptide coding residues 1327–1343 in the C-terminal region of the rat insulin receptor was phosphorylated at the threonine residue by protein kinase C in a phosphatidylserine and oleoylacetylglycerol dependent manner. Tryptic digest of this phosphopeptide migrated to the same position as the phosphothreonine containing peptide obtained from the β-subunit in two-dimensional phosphopeptide mapping. These data suggested that Thr 1336 of the insulin receptor is the site of phosphorylation by protein kinase C in intact cells

Association between Low Protein Intake and Mortality in Patients with Type 2 Diabetes

The aim of this study was to investigate the association between protein intake and mortality risk in patients with type 2 diabetes. We analyzed a pooled data of 2494 diabetic patients from two prospective longitudinal studies. Nutritional intake was assessed using a Food Frequency Questionnaire at baseline. Protein intake per body weight (kg) per day was categorized into quartile groups. Adjusted hazard ratios (HRs) and 95% confidence interval (CI) were calculated using Cox regression analysis. During the six-year follow-up, there were 152 incidents of all-cause mortality. The HR for mortality in the lowest quartile of protein intake per body weight compared with the highest quartile was 2.26 (95% CI: 1.34–3.82, p = 0.002) after adjustment for covariates. Subgroup analyses revealed significant associations between low protein intake and mortality in patients aged over 75 years or under 65 years. After further adjustment of the total energy intake, a significant association between protein intake and mortality remained in patients aged ≥ 75 years, whereas the association was attenuated in those aged < 65 years. Our results suggest that adequate protein intake is necessary in older diabetic patients over 75 years, whereas with diabetes, whereas whole optimal total energy intake is required in younger patients with type 2 diabetes

ApoE isoforms, treatment of diabetes and the risk of coronary heart disease

AIM: To analyze the risk of coronary heart disease in patients with type 2 diabetes mellitus (T2DM) receiving standard medical treatment