Glucose regulates the expression of the farnesoid X receptor in liver

An increased prevalence of hypertriglyceridemia and gallbladder disease occurs in patients with diabetes or insulin resistance. Hypertriglyceridemia is positively associated to gall bladder disease risk. The farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor that plays a key role in bile acid and triglyceride homeostasis. The mechanisms controlling FXR gene expression are poorly understood. This study evaluated whether FXR gene expression is regulated by alterations in glucose homeostasis. FXR expression was decreased in livers of streptozotocin-induced diabetic rats and normalized upon insulin supplementation. Concomitantly with diabetes progression, FXR expression also decreased in aging diabetic Zucker rats. In primary rat hepatocytes, D-glucose increased FXR mRNA in a dose- and time-dependent manner, whereas insulin counteracted this effect. Addition of xylitol, a precursor of xylulose-5-phosphate, to primary rat hepatocytes increased FXR expression to a comparable level as D-glucose. Finally, expression of the FXR target genes, SHP and apolipoprotein C-III, were additively regulated by D-glucose and FXR ligands. This study demonstrates that FXR is decreased in animal models of diabetes. In addition, FXR is regulated by glucose likely via the pentose phosphate pathway. Dysregulation of FXR expression may contribute to alterations in lipid and bile acid metabolism in patients with diabetes or insulin resistance.     

Immediate and delayed incorporations of events into dreams: further replication and implications for dream function

The incorporation of memories into dreams is characterized by two types of temporal effects: the day-residue effect, involving immediate incorporations of events from the preceding day, and the dream-lag effect, involving incorporations delayed by about a week. This study was designed to replicate these two effects while controlling several prior methodological problems and to provide preliminary information about potential functions of delayed event incorporations. Introductory Psychology students were asked to recall dreams at home for 1 week. Subsequently, they were instructed to select a single dream and to retrieve past events related to it that arose from one of seven randomly determined days prior to the dream (days 1-7). They then rated both their confidence in recall of events and the extent of correspondence between events and dreams. Judges evaluated qualities of the reported events using scales derived from theories about the function of delayed incorporations. Average ratings of correspondences between dreams and events were high for predream days 1 and 2, low for days 3 and 4 and high again for days 5-7, but only for participants who rated their confidence in recall of events as high and only for females. Delayed incorporations were more likely than immediate incorporations to refer to events characterized by interpersonal interactions, spatial locations, resolved problems and positive emotions. The findings are consistent with the possibility that processes with circaseptan (about 7 days) morphology underlie dream incorporation and that these processes subserve the functions of socio-emotional adaptation and memory consolidation.     

Selenium diet-supplementation improves cocaine-induced myocardial oxidative stress and prevents cardiac dysfunction in rats

Chronic cocaine abuse causes cardiac dysfunction and induces oxidative stress. The goal of this study was to evaluate whether an enhanced antioxidant pool, induced by the administration of selenium, may prevent the myocardial dysfunction induced by cocaine. Cocaine was administered for 7 days (15 mg/kg/day, i.p.) to rats pretreated for 4 weeks with selenium (1.16 mg/L/day, p.o.). Cardiac function was evaluated by cardiac index and left ventricular (LV) fractional shortening (FS) measured by echocardiography. The redox ratio and enzymatic activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured in the LV myocardium. Cocaine administration induced a cardiac dysfunction, as evidenced by a decrease in cardiac index and LV FS as well as by an increase in LV diameters. Moreover, antioxidant markers and redox ratio were altered in rats after cocaine exposure. Selenite supplementation induced a significant limitation of cardiac index and FS alterations observed after cocaine administration. This improvement in cardiac function was associated with a redox ratio recovery while SOD and GPX activities remained unchanged. Thus, selenite reversed both the oxidative stress and the contractile dysfunction induced by cocaine administration. These results suggest a major role of oxidative stress in the cocaine-induced cardiotoxicity.     

Effect of a nutritional intervention promoting the Mediterranean food pattern on electrophoretic characteristics of low-density lipoprotein particles in healthy women from the Québec City metropolitan area

The objective of the present study was to evaluate the effect of a nutritional intervention promoting the Mediterranean food pattern in free-living conditions on LDL electrophoretic characteristics in a group of seventy-one healthy women, aged between 30 and 65 years. The 12-week nutritional intervention consisted of two courses on nutrition and seven individual sessions with a dietitian. The first course provided information on the Mediterranean food pattern and the second was a cooking lesson. LDL peak particle diameter (LDL-PPD) and cholesterol levels in small (LDL-cholesterol<255 A) and large LDL fractions (LDL-cholesterol>260 A) were obtained by 2-16 % polyacrylamide gel electrophoresis of whole plasma. The sample was divided on the basis of baseline LDL-PPD using tertiles of the distribution (258.4 A and 260.0 A). Among the total sample of women, no significant change in LDL-PPD was observed in response to the nutritional intervention. However, subjects who at baseline were in the first tertile of the LDL-PPD distribution (<258.4 A) showed a significant increase in LDL-PPD and in the proportion of LDL %>260 A in response to the 12-week nutritional intervention (P<0.05). In contrast, LDL-PPD decreased significantly (P=0.007) among women with large LDL particles at baseline (LDL-PPD >260 A) while the proportion of LDL %<255 A and of LDL %>260 A remained unchanged. To conclude, changes in the food pattern, in response to a nutritional intervention promoting the Mediterranean food pattern, were accompanied by beneficial modifications in LDL electrophoretic characteristics in women who were characterised at baseline by smaller LDL particles.     

Proton beam therapy in the management of central nervous system tumors in childhood: the preliminary experience of the Centre de Protonthérapie d'Orsay

BACKGROUND: The purpose of the study was to evaluate clinical results and complications of a combination of proton and photon irradiation administered to 17 children with selected central nervous system (CNS) tumors. PROCEDURE: Between July 1994 and September 2000, 17 children, aged from 5 to 17 years (median: 12 years) with intracranial benign (6 cases) or malignant (11 cases) tumors, were treated with photons (median dose: 40 Gy; 24-54) and protons (median dose: 20 CGE; 9-31) at the Centre de Protonthérapie d'Orsay (CPO). RESULTS: Mean follow-up was 27 months (3-81). Two patients recurred locally (one marginal and one in situ). Fifteen patients are alive and doing well. Overall, 12, 24, and 36-month local control rate was 92 +/- 8% and, 12, 24, and 36-month overall survival rates were 93 +/- 6%, 83 +/- 11%, and 83 +/- 11%, respectively. Clinical initial symptoms remained stable or subsided in all patients. Early toxicities were in the expected range. CONCLUSIONS: With a mean 27 months follow-up, protontherapy was well tolerated for doses upto 69 CGE and with an excellent local control rate.     

The combined analysis of P-glycoprotein expression and activity predicts outcome in childhood acute lymphoblastic leukemia

The link between drug resistance and relapse was often suggested, but rarely demonstrated in long-range clinical studies. Since it is nowadays recommended to validate immunocytochemical results, the authors studied prospectively 52 acute lymphoblastic leukemia (ALL) patients with an immunocytochemical test and a functional flow cytometric test. The 4-year EFS and OS were 79.3% and 85.2%, respectively. Patients scoring positive in both tests had a significantly higher relapse rate and worse survival (log rank p = .007 and .047 for event-free survival and overall survival, respectively). Among the different prognostic variables evaluated, only the combination of P-gp expression and activity was a statistically significant parameter predicting relapse in childhood ALL.