Spiral Steroids During Pregnancy - It’s All About Potassium

This presentation has two parts. The 1st section describes processes during pregnancy with unknown, underlying biochemistry. The 2nd section shows the role of spiral steroids (SS) in these processes. 1] Fetal nutrition is provided through the placenta. Plasma electrolytes are 145 mM Na+ and 3-5 mM K+. Fetal K+ requirements reach a maximum during the 3rd trimester and must be pumped into cells against the plasma- intracellular gradient. 2] During the 3rd trimester, aldosterone is present in fetal plasma but the signal for endothelial sodium channel (ENaC) synthesis is blocked, leading to fetal Na+ wasting. The mechanism is unknown. 3] After parturition, infants are fed by nursing. Human milk contains 100 mM K+ and 10 mM Na+. Newborn infants are Na+ wasting, despite normal levels of aldosterone. Na+ wasting ends during the 2nd week post-partum without change in serum aldosterone levels. Infant physiology changes from K+ saving to Na+ saving by an unknown mechanism.4] Pre-eclampsia syndrome (proteinuria and hypertension during the 2nd half of pregnancy) affects 3-5 % of pregnant women. These symptoms usually resolve after parturition. 5] Women who have had pre-eclampsia have long-term, excess risk of cardiac and renal disorders. In 2018, we discovered Ionotropin, a SS. SS are phosphocholine esters of steroids with a lactone E-ring, similar to that of spironolactone. SS compounds function as aldosterone antagonists and regulate the NaK-ATPase. SS are involved in each of the 5 steps.1] SS are present in high levels in cord serum and were probably present in fetal plasma throughout gestation. SS stimulate the NaK-ATPase to pump K+ into cells against the gradient, just as does spironolactone.2] SS interfere with aldosterone signaling, just as does amiloride. This leads to increased fetal Na+ wasting, which becomes amniotic fluid.3] SS disappear from the infant circulation during the 1st week after parturition and decrease to adult levels during the 2nd week post-partum. Simultaneously, Na+ wasting ends and growth resumes.4] Women with pre-eclampsia have excess precursors for SS. These would be converted to SS in the fetal-placental unit and, during the 3rd trimester, diffuse into the maternal circulation and could cause pre-eclampsia.5] Ouabain, a plant toxin with a lactone E ring, causes renal and cardiac disorders in rat models. In women with pre-eclampsia, persistent excess SS may cause long-term damage. During gestation, the fetus requires K+ for growth. Our theory is, if (when) a fetus has inadequate K+ (hypokalemia), [a] the mother is signaled to produce SS precursors, [b] the feto-placental unit converts the precursors to SS, [c] fetal SS increase K+ transfer into tissues, and [d] excess SS transfuse back into the maternal circulation and damage maternal organs. We propose that pre-eclampsia is a side effect of fetal efforts to increase supply of K+. There are many possible origins of fetal hypokalemia.

Finite-frequency imaging of the global 410- and 660-km discontinuities using SS precursors

SUMMARY We report finite-frequency imaging of the global 410- and 660-km discontinuities using boundary sensitivity kernels for traveltime measurements made on SS precursors. The application of finite-frequency sensitivity kernels overcomes resolution limits in previous studies associated with large Fresnel zones of SS precursors and their interferences with other seismic phases. In this study, we calculate the finite-frequency sensitivities of SS waves and their precursors based on a single-scattering (Born) approximation in the framework of travelling-wave mode summation. The global discontinuity surface is parametrized using a set of triangular gridpoints with a lateral spacing of about 4°, and we solve the linear finite-frequency inverse problem (2-D tomography) based on singular value decomposition (SVD). The new global models start to show a number of features that were absent (or weak) in ray-theoretical back-projection models at spherical harmonic degree l > 6. The thickness of the mantle transition zone correlates well with wave speed perturbations at a global scale, suggesting dominantly thermal origins for the lateral variations in the mantle transition zone. However, an anticorrelation between the topography of the 410-km discontinuity and wave speed variations is not observed at a global scale. Overall, the mantle transition zone is about 2–3 km thicker beneath the continents than in oceanic regions. The new models of the 410- and 660-km discontinuities show better agreement with the finite-frequency study by Lawrence & Shearer than other global models obtained using SS precursors. However, significant discrepancies between the two models exist in the Pacific Ocean and major subduction zones at spherical harmonic degree >6. This indicates the importance of accounting for wave interactions in the calculations of sensitivity kernels as well as the use of finite-frequency sensitivities in data quality control.