Replacement of soy protein by casein in the cholesterol-free, semipurified diet of rabbits caused hypercholesterolemia within 7 days. After 36 days, the serum of casein-fed rabbits displayed elevated levels of free and esterified cholesterol and phospholipids, but not of triglycerides. Most of the excess of serum cholesterol in the casein group was localized in the LDL fraction, but there were marked variations in the density profile of the serum lipoproteins between individual rabbits. Dietary casein induced an increased content in liver of free and esterified cholesterol, but not of phospholipids and triglycerides. The molar ratio of free to esterified cholesterol in the liver was decreased by casein. In contrast, feeding casein resulted in an increase of this ratio in the serum.
Veal calves, aged about 1 week, were fed for 146 days milk replacement diets supplemented with various levels of cholesterol. Four groups consisting of 11 or 12 animals received diets to which 0, 0.19, 0.56 or 0.93% (on the basis of air-dry matter) cholesterol was added at the expense of fat. Cholesterol feeding significantly increased the level of serum cholesterol. This increase was either linear or S-shaped over the entire range of cholesterol feeding, depending on the time during which the calves were fed the diets. In the calves fed cholesterol, the ratio of free to esterified cholesterol in the serum was significantly increased. The ingestion of cholesterol markedly increased the cholesterol content of the VLDL, IDL and LDL fractions in the serum. When compared to the 0.56%-cholesterol diet, the inclusion of 0.93% cholesterol in the diet did not further increase the cholesterol concentrations in the IDL and LDL fractions. Upon density gradient ultracentrifugation of serum prestained for lipid with Sudan Black, it was observed that dietary cholesterol caused the HDL1 particles (1.063 less than d less than 1.092) to to shift towards a lower density range. Cholesterol feeding effected an increase in the level of serum triglycerides, the increase being already maximal with 0.19% cholesterol in the diet. Dietary cholesterol induced elevated concentrations of serum phospholipids, the elevation being proportional to the amount of cholesterol in the diet.
ObjectiveHLA‐DRB1*15:01 has been recently associated with interstitial lung disease (LD), eosinophilia, and drug reactions in systemic juvenile idiopathic arthritis (sJIA). Additionally, genetic variants in IL1RN have been linked to poor response to anakinra. We sought to reproduce these findings in a prospective cohort study of new‐onset sJIA patients treated with anakinra as first‐line therapy.MethodsHLA and IL1RN risk alleles were identified via whole genome sequencing. Treatment responses and complications were compared between carriers versus non‐carriers.ResultsSeventeen of 65 patients (26%) carried HLA‐DRB1*15:01, comparable to the general population, and there was enrichment for HLA‐DRB1*11:01, a known risk locus for sJIA. The rates of clinical inactive disease (CID) at 6 months, 1 and 2 years were generally high, irrespective of HLA‐DRB1 or IL1RN variants, but significantly lower in carriers of an HLA‐DRB1*11:01 allele. One patient, an HLA‐DRB1*15:01 carrier, developed sJIA‐LD. Of the three patients with severe drug reactions to biologics, one carried HLA‐DRB1*15:01. The prevalence of eosinophilia did not significantly differ between HLA‐DRB1*15:01 carriers and non‐carriers at disease‐onset (6.2% vs 14.9%, p=0.67) nor after the start of anakinra (35.3% versus 37.5% in the first 2 years of disease).ConclusionWe observed high rates of CID using anakinra as first‐line treatment irrespective of HLA‐DRB1 or IL1RN variants. Only one of the 17 HLA‐DRB1*15:01 carriers developed sJIA‐LD, and of the 3 patients with drug reactions to biologics, only one carried HLA‐DRB1*15:01. Although thorough monitoring for the development of drug hypersensitivity and refractory disease courses in sJIA, including sJIA‐LD remains important, our data support the early start of biological therapy in new‐onset sJIA patients irrespective of HLA‐DRB1 background or IL1RN variants.image
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