The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases.

The intestinal flora has long been thought to play a role either in initiating or in exacerbating the inflammatory bowel diseases (IBD). Host defenses, such as those mediated by the Toll-like receptors (TLR), are critical to the host/pathogen interaction and have been implicated in IBD pathophysiology. To explore the association of genetic variation in TLR pathways with susceptibility to IBD, we performed a replication study and pooled analyses of the putative IBD risk alleles in NFKB1 and TLR4, and we performed a haplotype-based screen for association to IBD in the TLR genes and a selection of their adaptor and signaling molecules. Our genotyping of 1539 cases of IBD and pooled analysis of 4805 cases of IBD validates the published association of a TLR4 allele with risk of IBD (odds ratio (OR): 1.30, 95% confidence interval (CI): 1.15-1.48; P=0.00017) and Crohn's disease (OR: 1.33, 95% CI: 1.16-1.54; P=0.000035) but not ulcerative colitis. We also describe novel suggestive evidence that TIRAP (OR: 1.16, 95% CI: 1.04-1.30; P=0.007) has a modest effect on risk of IBD. Our analysis, therefore, offers additional evidence that the TLR4 pathway - in this case, TLR4 and its signaling molecule TIRAP - plays a role in susceptibility to IBD.

Sex differences in adrenocortical structure and function. XX. The effects of gonadectomy and testosterone or estradiol replacement on cholesterol content and distribution in the gland.

Sex differences in the distribution of free and esterified cholesterol in the mitochondria and lipid droplets of the rat adrenal glands, as well as their dependence on gonadal hormones were studied. For these purposes intact, gonadectomized and gonadectomized-testosterone or estradiol replaced rats were employed. The concentration of free cholesterol [FC] as well as esterified cholesterol [EC] in full homogenates of decapsulated glands was higher in male than in female rats. Neither orchiectomy nor testosterone replacement had an effect on FC and EC concentration. Ovariectomy increased FC and EC concentration in full adrenal homogenates, an effect reversed by estradiol replacement. Similar changes were found in the lipid droplets. The concentration of FC and EC in the adrenal mitochondria was higher in male than in female rats. Orchiectomy increased the concentration of FC and decreased the concentration of EC. Testosterone administration resulted in further increase in FC concentration and restored EC concentration to the level of the control group. On the other hand ovariectomy increased FC and EC concentration, an effect reversed by estradiol replacement. Results obtained clearly showed that sex differences in FC and EC concentration in rat adrenal gland depend mainly on estradiol which lowers FC and EC concentration in the adrenal lipid droplets and mitochondria.

Effect of hyperthermia on blood levels of corticosterone and certain metabolites in rats during thiobutabarbital anaesthesia.

No changes were found in the serum levels of corticosterone, pyruvate and lactate in rats during general anaesthesia with thiobutabarbital (Brevinarcon) subjected to short-lasting hyperthermia in a high-temperature chamber (air temperature 50 degrees C, relative humidity 50%) in relation to a control group of rats during similar general anaesthesia at room temperature. However, in the serum of rats during hyperthermia (rectal temperature 40-41 degrees C) the glucose level was about 52% lower and FFA were about 39% lower than in rats kept under normothermic conditions (rectal temperature 36.5-37.5 degrees C) which may point to an increased requirement of tissues for energy-yielding substrates at higher body temperatures and/or increased insulin secretion.