Regulation of human cbfa1 gene transcription in osteoblasts by selective estrogen receptor modulators (SERMs)

Atrial natriuretic peptide (ANP) is a cardiac hormone that inhibits aldosterone secretion induced by all physiologic agonists. The purpose of this study is to explore ANP-induced changes in the phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS) and the steroidogenic acute regulatory protein (StAR), in AngII or K(+)-stimulated glomerulosa cells. The data show that ANP completely inhibits the phosphorylation of MARCKS and partially inhibits that of StAR in cells stimulated with K(+). ANP also partially inhibits MARCKS phosphorylation but does not affect StAR phosphorylation in cells stimulated with AngII. These effects appear to be cGMP-independent and at least partially dependent on inhibition of protein kinase C (PKC). To our knowledge, this is the first report of ANP modulating either MARCKS or StAR phosphorylation in [(32)P]-labeled cells. The data also support the hypothesis that ANP inhibits aldosterone secretion acting as a step involved in cholesterol transport to the mitochondria.     

Dose, timing, and duration of flaxseed exposure affect reproductive indices and sex hormone levels in rats.

Flaxseed ingestion produces large amounts of mammalian lignans. Since lignans have weak estrogenic/antiestrogenic properties, the objective of this study was to determine in rats whether exposure to 5% or 10% flaxseed affects sex hormone levels and reproductive indices when given at different developmental stages. Rats were exposed to either a basal diet (control), 5%, or 10% flaxseed diet starting at weaning on postnatal day (PND) 21 or continuously from gestation to PND 132 for lifetime exposure. Compared to the control, exposure to 5% or 10% flaxseed after weaning produced no marked reproductive effects, whereas lifetime flaxseed exposure caused significant changes that differed depending on the dose. In female rats, lifetime exposure to 5% flaxseed affected the reproductive tract as indicated by delayed puberty onset. In contrast, lifetime exposure to 10% flaxseed caused earlier puberty onset, higher relative ovarian weight, higher serum estradiol levels, and lengthened estrous cycles. In male rats, lifetime 10% flaxseed exposure raised serum testosterone and estradiol levels and produced higher relative sex organ weights and prostate cell proliferation. In contrast, lifetime exposure to 5% flaxseed reduced adult relative prostate weight and cell proliferation, suggesting potential protection against prostatic disease, although sex hormone levels were unaffected. In conclusion, flaxseed can potentially alter reproduction, depending on the dose and timing of exposure.     

Measurements of hydrocortisone and cortisone for longitudinal profiling of equine plasma by liquid chromatography–tandem mass spectrometry

The conventional detection of exogenous drugs in equine doping samples has been used for confirmation and subsequent prosecution of participants responsible. In recent years, alternative methods using indirect detection have been investigated due to the expanding number of pharmaceutical agents available with the potential of misuse. The monitoring of endogenous biomarkers such as hydrocortisone (HC) has been studied in equine urine with an international threshold of 1 μg/ml established; however, there is no current threshold for equine plasma. The aim of this research was to investigate plasma concentrations of HC and cortisone (C) in race day samples compared to an administration of Triamcinolone Acetonide (TACA). The reference population (n = 1150) provided HC (6 to 145 ng/ml) and C (0.7 to 13 ng/ml) levels to derive the HC to C ratio (HC/C). Population reference limits (PRLs) were proposed for HC/C values at 0.2 (lower) and 61 (upper). Administration of TACA resulted in down-regulation of HC/C values below the estimated PRLs for up to 96 h post-administration. This indirect detection period was longer than the detection of TACA for 72 h. The use of individual reference limits (IRLs) for HC/C values was investigated to support the Equine Biological Passport (EBP), an intelligence model developed by Racing NSW for longitudinal monitoring of biomarkers.     

恒河猴三硝基甲苯染毒后咖啡因清除率的变化

应用恒河猴做成亚慢性三硝基甲苯染毒（ＴＮＴ）模型，在染毒前，染毒中期和试验表明咖啡因在动物体内的清除呈一级动力学，半衰期为８。８８小时，这一结果说明咖啡因符合肝脏代射模型药物的要求。ＴＮＴ染毒后咖啡因清除率（ＣＬｃａ）下降，而同期血清甘胆酸（ＣＡ）浓度无变化。这一结果说明ＣＬｃａ可能比ＣＡ能列早地反映接触ＴＮＴ后的机体反应。染毒三个月后处死动物直接测定肝混合功能氧化酶（ＭＦＯ）活性，发现咖啡因清除     

Characterization and cloning of a novel phospholipase A(2) from the venom of Trimeresurus jerdonii snake.

A phospholipase A(2) (PLA(2)), called jerdoxin, was isolated from Trimeresurus jerdonni snake venom and partially characterized. The protein was purified by three chromatographic steps. SDS-polyacrylamide gel electrophoresis in the presence or absence of dithiothreitol showed that it had a molecular mass of 15 kDa. Jerdoxin had an enzymatic activity of 39.4 micro mol/min/mg towards egg yolk phosphatidyl choline (PC). It induced edema in the footpads of mice. In addition, jerdoxin exhibited indirect hemolytic activity. About 97% hemolysis was observed when 2 micro g/ml enzyme was incubated for 90 min in the presence of PC and Ca(2+). No detectable hemolysis was noticed when PC was not added. Ca(2+) was necessary for jerdoxin to exert its hemolytic activity, since only 52% hemolysis was seen when Ca(2+) was absent in the reaction mixture. Furthermore, jerdoxin inhibited ADP induced rabbit platelet aggregation and the inhibition was dose dependent with an IC(50) of 1.0 micro M. The complete amino acid sequence of jerdoxin deduced from cDNA sequence shared high homology with other snake venom PLA(2)s, especially the D 49 PLA(2)s. Also, the residues concerned to Ca(2+) binding were conserved. This is the first report of cDNA sequence of T. jerdonii venom PLA(2).