TL;DR: The species specificity which had been observed in rat and human transcortin for the species specific corticosteroid has not been found to be a general phenomenon.
Abstract: : The species specificity which had been observed in rat and human transcortin for the species specific corticosteroid has not been found to be a general phenomenon. The corticosteroidbinding proteins in the sera of various mammalian species belong to the alpha gloublin as was demonstrated by the method of equilibrium paper electrophoresis. Electrophoretic studies showed that the transcortin containing fraction of ran serum migrates faster than albumin at pH values below 7, whereas at higher pH it behaves as an alpha globulin. The alpha- acid glycoprotein (orsomucoid) has been prepared by a combination of precipitation and chromatographic procedures. The interaction of progesterone with this glycoprotein has been found to be highly dependent on temperature; the association constant decreases with increasing temperature. A strong dependency on pH has also been observed; the association constant is highest at pH 8 and decreases to about 1/20 of this value at pH 2.3. The number of binding sites for progesterone has been determined to be n = 1 at pH 7.4, 4 degrees C; the free energy of binding has the relatively high value of -7.5 kilocalories per mole. Partial removal of sialic acid from the orosomucoid preparations reduced the binding affinity for progesterone. In biological assay studies on the ligated uterus horn of the mouse it was observed that progesterone is inactivated by binding to the alphaacid blycoprotein.
TL;DR: Free cortisol is likely to be a better guide to cortisolemia in systemic infection because it corresponds more closely to illness severity.
Abstract: Context: Severe systemic infection leads to hypercortisolism. Reduced cortisol binding proteins may accentuate the free cortisol elevations seen in systemic infection. Recently, low total cortisol increments after tetracosactrin have been associated with increased mortality and hemodynamic responsiveness to exogenous hydrocortisone in septic shock (SS), a phenomenon termed by some investigators as relative adrenal insufficiency (RAI). Hypothesis: Free plasma cortisol may correspond more closely to illness severity than total cortisol, comparing SS and sepsis (S). Design: This was a prospective study. Setting: This study took place in a tertiary teaching hospital. Patients: Patients had SS (n = 45) or S (n = 19) or were healthy controls (HCs; n = 10). Aim: The aim of the study was to compare total with free cortisol, measured directly and estimated by Coolens’ method, corticosteroid-binding globulin (CBG), and albumin in patients with SS (with and without RAI) and S during acute illness, recovery, and conv...
TL;DR: Sequence comparison and phylogenetic analysis of sequences confirm that fish possess both GR and MR and that GR gene is duplicated and suggest that, whereas cortisol is certainly the physiological ligand for GR, this may not be the case for MR which showed high sensitivity for deoxycorticosterone (DOC) and aldosterone.
TL;DR: The data provide strong evidence that when CBG is inactivated or congenitally absent then more than 25% of the total cortisol appears in the free fraction with the remainder associated with albumin, which reflects a simple measure of functional corticosteroid-binding globulin.
TL;DR: A non-faradaic label-free cortisol biosensor was demonstrated using MoS2 nanosheets integrated into a nanoporous flexible electrode system, demonstrating a comparable dynamic range and limit of detection for the sensor.
Abstract: A non-faradaic label-free cortisol biosensor was demonstrated using MoS2 nanosheets integrated into a nanoporous flexible electrode system. Low volume (1-5 μL) sensing was achieved through use of a novel sensor stack design comprised of vertically aligned metal electrodes confining semi-conductive MoS2 nanosheets. The MoS2 nanosheets were surface functionalized with cortisol antibodies towards developing an affinity biosensor specific to the physiological relevant range of cortisol (8.16 to 141.7 ng/mL) in perspired human sweat. Sensing was achieved by measuring impedance changes associated with cortisol binding along the MoS2 nanosheet interface using electrochemical impedance spectroscopy. The sensor demonstrated a dynamic range from 1-500 ng/mL with a limit of detection of 1 ng/mL. A specificity study was conducted using a metabolite expressed in human sweat, Ethyl Glucuronide. Continuous dosing studies were performed during which the sensor was able to discriminate between four cortisol concentration ranges (0.5, 5, 50, 500 ng/mL) for a 3+ hour duration. Translatability of the sensor was shown with a portable form factor device, demonstrating a comparable dynamic range and limit of detection for the sensor. The device demonstrated a R2 correlation value of 0.998 when comparing measurements to the reported impedance values of the benchtop instrumentation.