A 9-cis beta-carotene-enriched diet inhibits atherogenesis and fatty liver formation in LDL receptor knockout mice

Our aim was to study the effect of 9-cis beta-carotene-rich powder of the alga Dunaliella bardawil on lipid profile, atherogenesis, and liver steatosis in high-fat diet-fed LDL receptor knockout mice. In 4 sets of experiments, mice were distributed into the following groups: control, fed an unfortified diet; Dunaliella 50, fed a diet composed of 50% 9-cis and 50% all-trans beta-carotene; Dunaliella 25, fed a diet containing 25% 9-cis and 75% all-trans beta-carotene; beta-carotene-deficient Dunaliella, fed beta-carotene-deficient Dunaliella powder; and all-trans beta-carotene, fed a synthetic all-trans beta-carotene. All fortified diets contained 0.6% total beta-carotene. Algal 9-cis beta-carotene was absorbed by the mice and accumulated in the liver. Synthetic all-trans beta-carotene was not converted to 9-cis beta-carotene. Dunaliella 50 inhibited high-fat diet-induced plasma cholesterol elevation by 40-63% and reduced cholesterol concentrations in the atherogenic VLDL and LDL. Atherosclerotic lesion area in mice treated with Dunaliella 50 was 60-83% lower compared with mice fed the high-fat diet alone. beta-Carotene-deficient Dunaliella did not influence plasma cholesterol and atherogenesis, suggesting that beta-carotene is essential for a Dunaliella protective effect. Moreover, by administrating Dunaliella powder containing different levels of 9-cis and all-trans beta-carotene isomers, we found that the effect on plasma cholesterol concentration and atherogenesis is 9-cis-dependent. Dunaliella 50 also inhibited fat accumulation and inflammation in the livers of mice fed a high-fat diet, which was accompanied by reduced mRNA levels of inflammatory genes. These results in mice suggest that 9-cis beta-carotene may have the potential to inhibit atherogenesis in humans.     

Significance of low level infliximab in the absence of anti-infliximab antibodies

AIM:To evaluate the prevalence of double negative(DN)sera and the mechanisms responsible for DN status.METHODS:Sera of inflammatory bowel disease patients treated with infliximab(IFX)were tested for drug/antibodies to infliximab(ATI)trough levels and the proportion of DN results was compared between a commercially available double antigen ELISA(with labeled IFX as the detection antibody)and an antilambda ELISA(with anti-human lambda chain detection antibody).Repeat testing with lower than customary serum dilution(1:10)was performed.Patients with DN status were matched with IFX+/ATI-controls and were followed-up for subsequent development of nontransient ATI to investigate if DN status precedes ATI.RESULTS:Of 67 sera obtained at time of loss of response,only 6/67(9%)were DN by anti-lambda ELISA compared to 27/67(40%)with double antigen ELISA(P0.001,Fisher’s Exact test).Of the latter27 sera,22%were also DN by anti-lambda ELISA,whereas 44%were actually IFX positive(IFX+ATI-),30%were ATI positive(IFX-ATI+)and 4%were double positive(IFX+ATI+).Re-testing using a 1:10 dilution converted most DN results into IFX+and/or ATI+status.Patients with DN status had shorter survival free of non-transient ATI compared with matched controls(log rank test,P0.001).In 9/30(30%)of these patients,non transient ATI occurred before and after the event at which the DN serum was obtained,supporting the view that a DN result may represent aparticular time-point along the two curves of ATI titer rise and infliximab drug level decline.CONCLUSION:DN status may result from false negative detection of IFX or ATI by double antigen ELISA,suggesting a transitional state of low-level immunogenicity,rather than non-immunological clearance.     

The epidemiology of volatile substance misuse among school children in Bogotá, Colombia

Volatile substance misuse (VSM) is increasing among Colombian youth. Rates and correlates of VSM, exposure-opportunity (EO) to VSM, and positive VSM intentions were examined in 2006 among 2,279 students (mean age 14.8 years) in 23 schools in Bogotá, Colombia. Sixteen percent experienced an EO, 3% reported past-year VSM, and 7-10% reported positive VSM intentions. Multilevel-logistic models revealed that VSM among friends was associated with past-year VSM (adjusted odds ratio (AOR) = 5.56, 95% confidence interval (CI) = 2.3-13.6) and VSM intention (AOR = 2.48, 95%CI = 1.6-3.9). Other correlates include male gender, a low perceived risk, and poor academic achievement. At-risk groups were identified, and targeted prevention strategies were suggested. The study's limitations are also noted.