Pharmacodynamics of Glyburide, Metformin, and Glyburide/Metformin Combination Therapy in the Treatment of Gestational Diabetes Mellitus

In gestational diabetes mellitus (GDM), women are unable to compensate for the increased insulin resistance during pregnancy. Data are limited regarding the pharmacodynamic effects of metformin and glyburide during pregnancy. This study characterized insulin sensitivity (SI), β-cell responsivity, and disposition index (DI) in women with GDM utilizing a mixed-meal tolerance test (MMTT) before and during treatment with glyburide monotherapy (GLY, n = 38), metformin monotherapy (MET, n = 34), or GLY and MET combination therapy (COMBO; n = 36). GLY significantly decreased dynamic β-cell responsivity (31%). MET and COMBO significantly increased SI (121% and 83%, respectively). Whereas GLY, MET, and COMBO improved DI, metformin (MET and COMBO) demonstrated a larger increase in DI (P = 0.05) and a larger decrease in MMTT peak glucose concentrations (P = 0.03) than subjects taking only GLY. Maximizing SI with MET followed by increasing β-cell responsivity with GLY or supplementing with insulin might be a more optimal strategy for GDM management than monotherapy

Pharmacodynamics of Metformin in Pregnant Women With Gestational Diabetes Mellitus and Nonpregnant Women With Type 2 Diabetes Mellitus

Gestational diabetes mellitus is a condition similar to type 2 diabetes mellitus (T2DM) in that patients are unable to compensate for the degree of insulin resistance, and both conditions are often treated with metformin. The comparative pharmacodynamic response to metformin in these 2 populations has not been studied. This study characterized insulin sensitivity, β-cell responsivity, and disposition index following a mixed-meal tolerance test utilizing a minimal model of glucose, insulin, and C-peptide kinetics before and during treatment with metformin. The study included women with gestational diabetes mellitus (n = 34), T2DM (n = 14), and healthy pregnant women (n = 30). Before treatment, the gestational diabetes mellitus group had significantly higher baseline (45%), dynamic (68%), static (71%), and total β-cell responsivity (71%) than the T2DM group. Metformin significantly increased insulin sensitivity (51%) as well as disposition index (97%) and decreased mixed-meal tolerance test peak glucose concentrations (8%) in women with gestational diabetes mellitus after adjustment for gestational age–dependent effects; however, in women with T2DM metformin only significantly affected peak glucose concentrations (22%) and had no significant effect on any other parameters. Metformin had a greater effect on the change in disposition index (Δ disposition index) in women with gestational diabetes mellitus than in those with T2DM (P =.01). In conclusion, response to metformin in women with gestational diabetes mellitus is significantly different from that in women with T2DM, which is likely related to the differences in disease severity

Paleomagnetism of Rumuruti chondrites suggests a partially differentiated parent body

International audienceDifferent types of magnetic fields were at work in the early solar system: nebular fields generated within the protoplanetary nebula, solar fields, and dynamo fields generated within the solar system solid bodies. Paleomagnetic studies of extraterrestrial materials can help unravel both the history of these magnetic fields, and the evolution of solar system solid bodies. In this study we studied the paleomagnetism of two Rumuruti chondrites (PCA 91002 and LAP 03639). These chondrites could potentially bear the record of the different fields (solar, nebular, dynamo fields) present during the early solar system. The magnetic mineralogy consists of pseudo-single domain pyrrhotite in LAP 03639 and pyrrhotite plus magnetite in PCA 91002. Paleomagnetic analyses using thermal and alternating field demagnetization reveal a stable origin trending component of magnetization. Fields of 12 mu T or higher are required to account for the magnetization in PCA 91002, but the timing and exact mechanism of the magnetization are unconstrained. In LAP 03639, considering various chronological constraints on the parent body evolution and on the evolution of the different sources of magnetic field in the early solar system, an internally-generated (dynamo) field of similar to 5 mu T recorded during retrograde metamorphism is the most likely explanation to account for the measured magnetization. This result indicates the existence of an advecting liquid core within the Rumuruti chondrite parent body, and implies that, as proposed for CV and H chondrites, this chondritic parent body is partially differentiated. (C) 2019 Elsevier B.V. All rights reserved

Neon diffusion kinetics in olivine, pyroxene and feldspar: retentivity of cosmogenic and nucleogenic neon

We performed stepwise degassing experiments by heating single crystals of neutron- or proton-irradiated olivine, pyroxene and feldspar to study diffusion kinetics of neon. This is important in evaluating the utility of these minerals for cosmogenic ²¹Ne measurements and, potentially, for Ne thermochronometry. Degassing patterns are only partially explained by simple Arrhenius relationships; most samples do not exhibit a precisely-determined activation energy in an individual diffusion domain. Regardless, we find clear differences in diffusion kinetics among these minerals. Based on sub-selected data, our estimates for neon diffusion kinetics (activation energy Ea and pre-exponential factor Do, assuming the analyzed fragments approximate the diffusion domain) in each mineral are as follows: for the feldspars, Ea ranges from !65 to 115 kJ/mol and <i>D</i>_o from 3.9 x 10^-3 to 7.1 x 10² cm²s^-1; for the pyroxenes, <i>E</i>_a ranges from !292 to 480 kJ/mol and Do from 1.6 x 10² to 2.9 x 10¹¹ cm²s^-1; for the olivines, <i>E</i>^a ranges from ~360 to 370 kJ/mol and <i>D</i>_o from 1.5 x 10⁶ to 5.0 x 10⁶ cm²s^-1. Differences in these parameters are broadly consistent with the expected effect of structural differences between feldspar, and olivine and pyroxene. These results indicate that cosmogenic 21Ne will be quantitatively retained within olivine and pyroxene at Earth surface temperatures over geological timescales. The diffusion kinetics for feldspars, on the other hand, predicts that ²¹Ne retention at Earth surface temperatures will vary significantly with domain size, crystal microtexture, surface temperature, and exposure duration. Quantitative retention is expected only in favorable conditions. This conclusion is reinforced by additional measurements of cosmogenic ²¹Ne in coexisting quartz and feldspar from naturally irradiated surface samples; sanidine from a variety of rhyolitic ignimbrites exhibits quantitative retention, whereas alkali–feldspar from several granites does not

(U-Th)/He and 4He/3He Thermochronology of Secondary Oxides in Faults and Fractures: A Regional Perspective From Southeastern Arizona

Fe- and Mn-oxides are common secondary minerals in faults, fractures, and veins and potentially record information about the timing of fluid movement through their host rocks. These phases are difficult to date by most radioisotopic techniques, but relatively high concentrations of U and Th make the (U-Th)/He system a promising approach. We present new petrographic, geochronologic and thermochronologic analyses of secondary oxides and associated minerals from fault zones and fractures in southeastern Arizona. We use these phases in attempt to constrain the timing of fluid flow and their relationship to magmatic, tectonic, or other regional processes. In the shallowly exhumed Galiuro Mountains, Fe-oxide (U-Th)/He dates correspond to host-rock crystallization and magmatic intrusions from ca. 1.6 to 1.1 Ga. Step-heating 4He/3He experiments and polydomain diffusion modeling of 3He release spectra on these samples are consistent with a crystallite size control on He diffusivity, and little fractional loss of radiogenic He since formation in coarse-grained hematite, but large losses from fine-grained Mn-oxide. In contrast to Proterozoic dates, Fe- and Mn-oxides from the Catalina-Rincon and Pinaleño metamorphic core complexes are exclusively Cenozoic, with dates clustering at ca. 24, 15, and 9 Ma, which represent distinct cooling or fluid-flow episodes during punctuated periods of normal faulting. Finally, a subset of Fe-oxides yield dates of ca. 5 Ma to 6 ka and display either pseudomorphic cubic forms consistent with oxidative retrogression of original pyrite or magnetite, or fine-grained botryoidal morphologies that we interpret to represent approximate ages of recrystallization or pseudomorphic replacement at shallow depths. © 2021 The Authors.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Troctolite 76535: A sample of the Moon's South Pole-Aitken basin?

© 2019 Elsevier Inc. Lunar samples returned by the Apollo program have provided insights into numerous solar system processes. However, no samples were returned from the lunar farside, where one of the Moon's most geologically important features resides: the 2500-km-diameter South Pole-Aitken basin (SPA). Here, we explore the hypothesis that lunar troctolite 76535 was excavated by SPA. This hypothesis is motivated by the sample's low peak shock pressure (<6 GPa), its substantial depth of origin (45–65 km), and its ancient 40Ar/39Ar age of 4.25 Ga. We use hydrodynamic simulations of crater formation to show that for vertically incident impactors, SPA is the only known basin that can excavate material from the depth and shock pressure range relevant to 76535. The thermal history of 76535 also rules out excavation where a magma ocean was locally present. However, for the vertical impacts modeled, delivery of 76535 to the Apollo 17 site, where it was collected, requires a second impact event that preserved the sample's low shock state. An alternative interpretation of the SPA origin is that 76535 originates from the Serenitatis, Fecunditatis, or Australe basins, if the inferred origin depth of 76535 is in error by ~20 km, or its inferred peak shock pressure is in error by a factor of ~2. These basins could also be candidates for excavating 76535, if oblique impacts yield lower shock pressures of material excavated from the relevant depth. If troctolite 76535 is in fact a sample of SPA, we find that its 4.25 Ga excavation age and the density of large (100–300 km diameter) impact basins within and on the rim of SPA are consistent with the monotonically decaying Neukum (1983) chronology

Detached-Eddy Simulation of Slat and Flap Aerodynamics for a High-Lift Wing

Three-dimensional multi-element wings are simulated to investigate slat and flap aerodynamics using Detached-Eddy Simulation. The computations are performed by solving the Navier-Stokes equations on unstructured grids. All of the computed cases include the main wing with a half-span flap deflected to 39 degrees and a three-quarter-span slat deflected to 6 degrees. Computations of the model, which simulates a landing configuration at 10 degrees angle of attack and a chord-based Reynolds number of 3.7 million, are validated with surface pressure measurements acquired at the NASA Ames 7- by 10-Foot Wind Tunnel. The results increase the computational knowledge of how to accurately model the flow physics of a multi-element wing with three-dimensional flow by using Detached-Eddy Simulation