Identification of polymorphisms in the human 11beta-hydroxysteroid dehydrogenase type 2 gene promoter: functional characterization and relevance for salt sensitivity

Reduced activity of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays a role in essential hypertension and the sensitivity of blood pressure to dietary salt. Nonconservative mutations in the coding region are extremely rare and do not explain the variable 11beta-HSD2 activity. We focused therefore on the 5'-regulatory region and identified and characterized the first promoter polymorphisms. Transfections of variants G-209A and G-126A into SW620 cells reduced promoter activity and affinity for activators nuclear factor 1 (NF1) and Sp1. Chromatin immunoprecipitation revealed Sp1, NF1, and glucocorticoid receptor (GR) binding to the HSD11B2 promoter. Dexamethasone induced expression of mRNA and activity of HSD11B2. GR and/or NF1 overexpression increased endogenous HSD11B2 mRNA and activity. GR complexes cooperated with NF1 to activate HSD11B2, an effect diminished in the presence of the G-209A variant. When compared to salt-resistant subjects (96), salt-sensitive volunteers (54) more frequently had the G-209A variant, higher occurrence of alleles A4/A7 of polymorphic microsatellite marker, and higher urinary ratios of cortisol to cortisone metabolites. First, we conclude that the mechanism of glucocorticoid-induced HSD11B2 expression is mainly mediated by cooperation between GR and NF1 on the HSD11B2 promoter and, second, that the newly identified promoter variants reduce activity and cooperation of cognate transcription factors, resulting in diminished HSD11B2 transcription, an effect favoring salt sensitivity.

Salt sensitivity of children with low birth weight

Compromised intrauterine fetal growth leading to low birth weight (<2500 g) is associated with adulthood renal and cardiovascular disease. The aim of this study was to assess the effect of salt intake on blood pressure (salt sensitivity) in children with low birth weight. White children (n=50; mean age: 11.3+/-2.1 years) born with low (n=35) or normal (n=15) birth weight and being either small or appropriate for gestational age (n=25 in each group) were investigated. The glomerular filtration rate was calculated using the Schwartz formula, and renal size was measured by ultrasound. Salt sensitivity was assigned if mean 24-hour blood pressure increased by >or=3 mm Hg on a high-salt diet as compared with a controlled-salt diet. Baseline office blood pressure was higher and glomerular filtration rate lower in children born with low birth weight as compared with children born at term with appropriate weight (P<0.05). Salt sensitivity was present in 37% and 47% of all of the low birth weight and small for gestational age children, respectively, higher even than healthy young adults from the same region. Kidney length and volume (both P<0.0001) were reduced in low birth weight children. Salt sensitivity inversely correlated with kidney length (r(2)=0.31; P=0.005) but not with glomerular filtration rate. We conclude that a reduced renal mass in growth-restricted children poses a risk for a lower renal function and for increased salt sensitivity. Whether the changes in renal growth are causative or are the consequence of the same abnormal "fetal programming" awaits clarification.

Parameter identification of a copper-zeolite SCR catalyst model using reactor data

The selective catalytic reduction system is a well established technology for NOx emissions control in diesel engines. A one dimensional, single channel selective catalytic reduction (SCR) model was previously developed using Oak Ridge National Laboratory (ORNL) generated reactor data for an iron-zeolite catalyst system. Calibration of this model to fit the experimental reactor data collected at ORNL for a copper-zeolite SCR catalyst is presented. Initially a test protocol was developed in order to investigate the different phenomena responsible for the SCR system response. A SCR model with two distinct types of storage sites was used. The calibration process was started with storage capacity calculations for the catalyst sample. Then the chemical kinetics occurring at each segment of the protocol was investigated. The reactions included in this model were adsorption, desorption, standard SCR, fast SCR, slow SCR, NH3 Oxidation, NO oxidation and N2O formation. The reaction rates were identified for each temperature using a time domain optimization approach. Assuming an Arrhenius form of the reaction rates, activation energies and pre-exponential parameters were fit to the reaction rates. The results indicate that the Arrhenius form is appropriate and the reaction scheme used allows the model to fit to the experimental data and also for use in real world engine studies.

Electrolysis of Molten Mixtures of Galena and Lead Chloride.

Electrolysis of molten mixtures of lead chloride and galena was carried out under various conditions of temperature, time, composition, and current densities; without a diaphram, and with various diaphrams. Continuous runs, with necessary additions of lead sulfide and lead chloride to maintain a melt of the proper composition, were attempted on a small scale.

The Electroformation of Lithium-Lead Alloys from Molten Electrolytes

An attempt was made to make lead-lithium alloys by electrodeposition of lithium using a molten bath and a molten lead cathode.The variables taken into consideration were: composition of the melt, temperature of the melt, and current density. The purpose of changing these factors was to determine what effect each had on the current efficiency.

The Electrodeposition of Chromium from Trivalent Salt Solutions

The enormous number of previous experiments and researches for the improvement of the commercial chromic acid bath, did not succeed even in the partial elimination of any one of the disadvantages of chromic acid bath. This led the author to believe that the poor performance is an inherent quality of the chromic acid bath, and is due to the fact that the deposition occurs from the higher state of oxidation.

Corrosion Testing of Iron-Tin Alloys by the Salt Spray Method

The purpose of this study was to determine the rela­tive rate of corrosion of iron-tin alloys containing low percentages of tin. Since in the world today, a great deal of work is being done to develop large tin deposits and new methods devised to treat these ores, it is possible that the metal will become abundant and will obtain a more important position in the metal industry.

Geology and Ore Deposits of the Salt Chuck-Rush and Brown Mine Area Prince of Wales Island, Alaska

The Salt Chuck, Rush and Brown, and adjacent mines and claims form an area of approximately 15 square miles near the head of Kasaan Bay about 10 miles northwest of the village of Kasaan on Prince of Wales Island in southeastern Alaska. It is an area of moderate relief in which the hills rise from the water’s edge to heights of some 500 feet. Most of the area is covered with dense vegetation and muskeg.

Body fluids and salt metabolism - Part I

ABSTRACT: There is a high frequency of diarrhea and vomiting in childhood. As a consequence the focus of the present review is to recognize the different body fluid compartments, to clinically assess the degree of dehydration, to know how the equilibrium between extracellular fluid and intracellular fluid is maintained, to calculate the effective blood osmolality and discuss both parenteral fluid requirments and repair.

[Hyponatraemia in patients with neurosurgical disorders: SIADH or cerebral salt wasting syndrome?]

Patients with neurosurgical disorders often present with hyponatraemia. Two mechanisms account for hyponatraemia in these patients: the Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) and Cerebral Salt Wasting Syndrome (CSWS). The two entities differ in their volume status. In SIADH, volume is expanded due to ADH-mediated renal water retention, but in CSWS, volume is diminished as a consequence of renal salt wasting, most likely attributable to an increased secretion of Brain Natriuretic Peptide (BNP) and Artrial Natriuretic Peptide (ANP). Since it is clinically difficult to distinguish between these two entities, fluid management has to be performed carefully. Salt and fluid replacement appears to be indicated in CSWS, whereas fluid restriction might be the primary approach in patients with SIADH.