.We report the synthesis, anti-inflammatory and antioxidant activities of novel quinoxaline and quinoxaline 1,4-di-N-oxide derivatives. Microwave assisted methods have been used in order to optimize reaction times and to improve the yields. The tested compounds presented important scavenging activities and promising in vitro inhibition of soybean lipoxygenase. Two of the best lipoxygenase inhibitors (compounds 7b and 8f) were evaluated as in vivo antiinflammatory agents using the carrageenin-induced edema model. One of them (compound 7b) showed important in vivo anti-inflammatory effect (41%) similar to that of indomethacin (47%) used as the reference drug.

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Zonation affects liver parenchymal cell function and metabolism as well as nonparenchymal cell activation, but whether VLDL production is zonated has yet to be elucidated. Infection induces enhanced VLDL secretion by the liver. Ex vivo studies were undertaken to examine the liver heterogeneity for VLDL formation and secretion and their in vivo response to endotoxin. Highly pure periportal (PP) and perivenous (PV) hepatocytes were isolated from fasted lipopolysaccharide-treated, fasted, and fed rats. They were used to assess their capacity to release VLDL-apolipoprotein B (apoB) and lipid classes in relation to de novo lipid synthesis and the expression of genes crucial to VLDL production. Despite the common superior ability of PP hepatocytes for lipid release and zonal differences in lipid synthesis, zonated secretion of VLDL particles was observed in septic but not in normal fed or fasted livers. The endotoxininduced apoB secretion was more accentuated in PP hepatocytes; this was accompanied by a preferential PP increase in apoB and microsomal triglyceride transfer protein mRNA levels, whereas lipogenesis indicators were, if anything, similarly modified in hepatocytes of either acinar origin. We conclude that PP and PV hepatocytes exhibited similar capabilities for VLDL formation/secretion in normal conditions; however, the endotoxic pressure did zonate periportally. Septic hyperlipidemia and hyperlipoproteinemia have been postulated to be components of the innate defense against infection in humans and experimental models (1). The insertion of the lipid A component of Gram-negative bacterial lipopolysaccharide (LPS; or endotoxin) in the phospholipid layer of lipoproteins diminishes toxicity (2), as it enables endotoxin clearance and excretion by hepatic parenchymal cells (3). Septic hypertriglyceridemia is mainly caused by the accumulation of VLDL particles in the plasma (4) attributable to many changes in their metabolism (5, 6; see recent review in 7), including increased secretion by the liver (8).VLDL particles are assembled at the endoplasmic reticulum (ER) of hepatocytes in a process that depends absolutely upon the cellular availability of lipids, such as triglycerides (TGs), phospholipids, cholesterol, and cholesteryl esters, to correctly translate and translocate apolipoprotein B (apoB) to the lumen. ApoB-100 and apoB-48 are the essential apolipoproteins for VLDL assembly in the rat (9). They are expressed in excess, and the protein that is not lipidated to a sufficient extent is targeted to and eventually degraded by proteasomes (10). Correct apoB lipidation and translocation are controlled by the microsomal triglyceride transfer protein (MTP), whose binding and lipid transfer activities are probably the major determinant in VLDL secretion (11-13). The assembly of VLDL is a complex process that includes two major lipidation steps. A relatively small, dense, TG-poor lipoprotein particle is formed in the ER by cotranslational loading of apoB chains with lipid. Then, bulk lipidation and final m...

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A detailed evaluation of the rennin–angiotensin system by concurrent determinations of plasma renin activity, renal renin activity, and juxtaglomerular index in newborn dogs during the first 15 days of extrauterine life is described. Findings show that the plasma renin activity is significantly higher for the first 2 weeks of extrauterine life when compared with the values found in adult dogs, and that the renal renin activity is slightly greater despite a very low juxtaglomerular index with a few granular cells, mostly located in the juxtamedullary cortex. Stimulation (peritoneal dialysis) of renin release resulted in a marked increase in plasma renin activity. The juxtaglomerular index was not modified by the stimulation whereas the renal renin activity decreased slightly. From these results, it is suggested that the formation and secretion of renin is well developed in kidneys of newborn dogs despite the absence of demonstrable juxtaglomerular cell granules.