A 28-day repeat dose toxicity study of steroidal glycoalkaloids, α-solanine and α-chaconine in the Syrian Golden hamster

Glycoalkaloids α-solanine and α-chaconine are naturally present toxicants in the potato plant (Solanumtuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of α-solanine to α-chaconine may determine the degree and nature of the glycoalkaloid toxicity in potatoes, as the toxicity of the two alkaloids act synergistically. The aim of the present study was to investigate whether an altered ratio of α-solanine and α-chaconine would reduce the toxicity of the glycoalkaloids. The Syrian Golden hamster was given daily doses of α-solanine and α-chaconine by gavage for 28 days. Doses of up to 33.3 mg total glycoalkaloids/kg body weight were applied in ratios of 1:3.7 and 1:70 (α-solanine:α-chaconine). Administration of the highest doses of both ratios resulted in distended and fluid filled small intestines and stomach. Animals receiving the ratio with the reduced content of α-solanine were less affected compared to those receiving the other ratio. Gene expression profiling experiments were conducted using RNA from epithelial scrapings from the small intestines of the hamsters administered the highest doses of the glycoalkaloid treatments. In general, more differential gene expression was observed in the epithelial scrapings of the hamsters fed the ratio of 1:3.7. Mostly, pathways involved in lipid and energy metabolism were affected by the ratio of 1:3.7.     

FS02.4Differential gene expression in allergen‐activated peripheral blood mononuclear cells from allergic patients

Allergic contact dermatitis is a delayed type hypersensitivity reaction mediated by allergen specific T‐lymphocytes. Allergen exposure leads to the activation of specific T‐lymphocytes, which subsequently start to produce and release a vast array of cytokines and chemokines. However, the list of relevant genes taking part in the elicitation phase of contact dermatitis is not complete. In this study, we evaluate the use of the high‐density microarray technology, which enable us to assess the global gene expression in allergen‐stimulated peripheral blood mononuclear cells (PBMC). We included 3 chromium‐allergic patients and 3 non‐allergic controls in the study. Cultures of PBMC were established from each participant and stimulated with 100 ug/ul CrCl3 or media alone. The cell cultures were grown for 24 hours and the gene expression was analysed using an Affymetrix GeneChip(R) Array. Of the genes that exhibited differences of expression (p < 0.01) in allergen‐activated PBMC from patients compared to controls, 54%(159/294) displayed increased activity and 46%(136/294) displayed decreased activity. Of the 159 up‐regulated genes, 41 genes had a fold change above 1.50 and 30 genes among the 136 down‐regulated genes had a fold change below ‐1.5. A significant number of the genes that showed differential expression in the cell cultures established from the allergic patients are known to be involved in immune responses and inflammation. The data indicates that the method of microarrays is a valuable tool for investigating the gene expression profile in our model system for allergic contact dermatitis.     

Increased plant sterol and stanol levels in brain of Watanabe rabbits fed rapeseed oil derived plant sterol or stanol esters

Foods containing plant sterol or stanol esters can be beneficial in lowering LDL-cholesterol concentration, a major risk factor for CVD. The present study examined whether high dietary intake of rapeseed oil (RSO) derived plant sterol and stanol esters is associated with increased levels of these components in brain tissue of homozygous and heterozygous Watanabe rabbits, an animal model for familial hypercholesterolemia. Homozygous animals received either a standard diet, RSO stanol or RSO sterol ester while heterozygous animals were additionally fed with 2 g cholesterol/kg to the respective diet form for 120 d (n 9 for each group). Concentrations of cholesterol, its precursor lathosterol, plant sterols and stanols in brain and additionally in liver and plasma were determined by highly sensitive GC-MS. High-dose intake of RSO derived plant sterols and stanols resulted in increased levels of these components in plasma and liver. In brain a limited uptake of plant sterols and stanols was proven, indicating that these compounds passed the blood-brain barrier and may be retained in the brain tissue of Watanabe rabbits. Plant stanol ester feeding lowered plant sterol levels in brain, liver, and plasma. Cholesterol synthesis in brain, indicated by lathosterol, a local surrogate cholesterol synthesis marker, does not seem to be affected by plant sterol or stanol ester feeding. We conclude that high dose intake of plant sterol and stanol esters in Watanabe rabbits results in elevated concentrations of these components not only in the periphery but also in the central nervous system.     

Post-operative acute kidney injury and five-year risk of death,myocardial infarction,and stroke among elective cardiac surgical patients: a cohort study

Introduction

The prognostic impact of acute kidney injury (AKI) on long-term clinical outcomes remains controversial. We examined the five-year risk of death, myocardial infarction, and stroke after elective cardiac surgery complicated by AKI.

Methods

We conducted a cohort study among adult elective cardiac surgical patients without severe chronic kidney disease and/or previous heart or renal transplant surgery using data from population-based registries. AKI was defined by the Acute Kidney Injury Network (AKIN) criteria as a 50% increase in serum creatinine from baseline level, acute creatinine rise of ≥26.5 μmol/L (0.3 mg/dL) within 48 hours, and/or initiation of renal replacement therapy within five days after surgery. We followed patients from the fifth post-operative day until myocardial infarction, stroke or death within five years. Five-year risk was computed by the cumulative incidence method and compared with hazards ratios (HR) from a Cox proportional hazards regression model adjusting for propensity score.

Results

A total of 287 (27.9%) of 1,030 patients developed AKI. Five-year risk of death was 26.5% (95% CI: 21.2 to 32.0) among patients with AKI and 12.1% (95% CI: 10.0 to 14.7) among patients without AKI. The corresponding adjusted HR of death was 1.6 (95% CI: 1.1 to 2.2). Five-year risk of myocardial infarction was 5.0% (95% CI: 2.9 to 8.1) among patients with AKI and 3.3% (95% CI: 2.1 to 4.8) among patients without AKI. Five-year risk of stroke was 5.0% (95% CI: 2.8 to 7.9) among patients with AKI and 4.2% (95% CI: 2.9 to 5.8) among patients without AKI. Adjusted HRs were 1.5 (95% CI: 0.7 to 3.2) of myocardial infarction and 0.9 (95% CI: 0.5 to 1.8) of stroke.

Conclusions

AKI, within five days after elective cardiac surgery, was associated with increased five-year mortality and a statistically insignificant increased risk of myocardial infarction. No association was seen with the risk of stroke.