Natural and Synthetic Corticosteroids Inhibit Uptake\u3csub\u3e2\u3c/sub\u3e-Mediated Transport in CNS Neurons

In addition to exerting actions via mineralocorticoid and glucocorticoid receptors, corticosteroids also act by inhibiting uptake2, a high-capacity monoamine transport system originally described in peripheral tissues. Recent studies have demonstrated that uptake2 transporters are expressed in the brain and play roles in monoamine clearance, suggesting that they mediate some corticosteroid effects on physiological and behavioral processes. However, the sensitivity of brain uptake2 to many natural and synthetic corticosteroids has not been characterized. Cultured rat cerebellar granule neurons (CGNs) were previously shown to exhibit corticosterone-sensitive accumulation of the uptake2 substrate1-methyl-4-phenylpyridinium (MPP+). We examined the expression of uptake1 and uptake2 transporters in CGNs, and tested the effects of a variety of natural and synthetic corticosteroids on accumulation of [3H]-MPP+ by these cells. Cultured rat CGNs expressed mRNA for three uptake2-like transporters: organic cation transporters 1 and 3, and the plasma membrane monoamine transporter. They did not express mRNA for the dopamine or norepinephrine transporters, and expressed very little mRNA for the serotonin reuptake transporter. Accumulation of [3H]-MPP+ by CGNs was dose-dependently inhibited by corticosterone and decynium-22, known inhibitors of uptake2. Accumulation of MPP+ was also dose-dependently inhibited, with varying efficacies, by aldosterone, 11-deoxycorticosterone, cortisol, and cortisone, and by the synthetic glucocorticoids betamethasone, dexamethasone and prednisolone, and the glucocorticoid receptor antagonist RU38486. These studies demonstrate that uptake2 in the CNS is inhibited by a variety of natural and synthetic corticosteroids, and suggest that inhibition of uptake2-mediated monoamine clearance may underlie some behavioral and physiological effects of these hormones

Bottom-up or Top-down? Removing the Privacy Law Obstacles to Healthcare Reform in the National Healthcare Crisis

Issues of healthcare availability and quality are among the most profound facing our nation. If a high-quality, accessible healthcare system of a truly national nature is to be devised, electronic connectivity—including increased use of electronic medical records and similar technological advances—must be a key feature. Yet such connectivity may give rise to patients’ concerns regarding the privacy of their medical information. Because such concerns demand respect, a challenge lies in balancing patients’ privacy interests against the important information-sharing interests underlying a national healthcare network. The Health Insurance Portability & Accountability Act (HIPPAA) is a key federal law that addresses many privacy issues regarding patients’ medical information, but HIPAA does not preempt state laws that furnish greater privacy protection than HIPAA provides. Accordingly, there exists a patchwork quilt of differing privacy protection provisions. This Article explores the issues just outlined and stresses the importance of a stronger federal role in standardizing medical information privacy rules, so that the current patchwork quilt of privacy regulations does not impede the development of a national healthcare network

Bottom-up or Top-down? Removing the Privacy Law Obstacles to Healthcare Reform in the National Healthcare Crisis

Issues of healthcare availability and quality are among the most profound facing our nation. If a high-quality, accessible healthcare system of a truly national nature is to be devised, electronic connectivity—including increased use of electronic medical records and similar technological advances—must be a key feature. Yet such connectivity may give rise to patients’ concerns regarding the privacy of their medical information. Because such concerns demand respect, a challenge lies in balancing patients’ privacy interests against the important information-sharing interests underlying a national healthcare network. The Health Insurance Portability & Accountability Act (HIPPAA) is a key federal law that addresses many privacy issues regarding patients’ medical information, but HIPAA does not preempt state laws that furnish greater privacy protection than HIPAA provides. Accordingly, there exists a patchwork quilt of differing privacy protection provisions. This Article explores the issues just outlined and stresses the importance of a stronger federal role in standardizing medical information privacy rules, so that the current patchwork quilt of privacy regulations does not impede the development of a national healthcare network

Predictions of children’s emotionality from evolutionary and epigenetic hypotheses

Sex-dependent effects of mismatched prenatal-postnatal maternal conditions are predicted by combining two evolutionary hypotheses: that foetal conditions provide a forecast of likely postnatal environments (Predictive Adaptive Response), and that the female foetus is better adapted than the male to maternal adversity (Trivers-Willard hypothesis). Animal studies have implicated glucocorticoid mechanisms modifiable by effects of postnatal tactile stimulation on glucocorticoid receptor gene expression. In this study we examined behavioural predictions in humans based on these evolutionary and epigenetic models. Mothers in a general population cohort provided self-reported anxiety scores at 20 weeks pregnancy, and at 9 weeks, 14 months and 3.5 years postpartum, and frequency of infant stroking at 9 weeks. Mothers and teachers reported child symptoms at 7 years. SEM models with maximum-likelihood estimates made use of data from 887 participants. There was a three-way interaction between prenatal and postnatal anxiety and maternal stroking in the prediction of irritability, seen only in girls. This arose because lower maternal stroking was associated with higher irritability, only in the mismatched, low-high and high-low maternal anxiety groups. We provide evidence that mechanisms likely to have evolved well before the emergence of humans, contribute to the development of children’s emotionality and risk for depression

Corticosterone Acts in the Nucleus Accumbens to Enhance Dopamine Signaling and Potentiate Reinstatement of Cocaine Seeking

Stressful life events are important contributors to relapse in recovering cocaine addicts, but the mechanisms by which they influence motivational systems are poorly understood. Studies suggest that stress may “set the stage” for relapse by increasing the sensitivity of brain reward circuits to drug-associated stimuli. We examined the effects of stress and corticosterone on behavioral and neurochemical responses of rats to a cocaine prime after cocaine self-administration and extinction. Exposure of rats to acute electric footshock stress did not by itself reinstate drug-seeking behavior but potentiated reinstatement in response to a subthreshold dose of cocaine. This effect of stress was not observed in adrenalectomized animals, and was reproduced in nonstressed animals by administration of corticosterone at a dose that reproduced stress-induced plasma levels. Pretreatment with the glucocorticoid receptor antagonist RU38486 did not block the corticosterone effect. Corticosterone potentiated cocaine-induced increases in extracellular dopamine in the nucleus accumbens (NAc), and pharmacological blockade of NAc dopamine receptors blocked corticosterone-induced potentiation of reinstatement. Intra-accumbens administration of corticosterone reproduced the behavioral effects of stress and systemic corticosterone. Corticosterone treatment acutely decreased NAc dopamine clearance measured by fast-scan cyclic voltammetry, suggesting that inhibition of uptake2-mediated dopamine clearance may underlie corticosterone effects. Consistent with this hypothesis, intra-accumbens administration of the uptake2 inhibitor normetanephrine potentiated cocaine-induced reinstatement. Expression of organic cation transporter 3, a corticosterone-sensitive uptake2 transporter, was detected on NAc neurons. These findings reveal a novel mechanism by which stress hormones can rapidly regulate dopamine signaling and contribute to the impact of stress on drug intake

Preliminary Evaluation of the Eagle Flat Region Hudspeth County, Texas

Preliminary evaluation of the Eagle Flat region, as designated by the Texas Legislature, indicates several areas that may have geologic and hydrologic conditions favorable for further evaluation as potential siting areas for the Texas low-level radioactive waste repository. This determination is based on a review of available data regarding surface drainage, thickness and character of alluvial fill, depth to groundwater, and apparent presence or absence of such features as late Cenozoic faults, fissures, known natural resources, and evidence of erosion. Some general siting areas have been identified that contain several sections that appear to have favorable characteristics. Examples of apparently favorable general siting areas are east of Yucca Mesa, south of Eagle Flat Mountain, and north of Little Hills. Our preliminary assessment is that, of the three areas cited above, the Yucca Mesa location should be given priority consideration. Initial flooding and drainage analysis indicates that the Yucca Mesa site includes sufficient surface areas unaffected by flooding. There are no known fissures or late Cenozoic faults. Depth to groundwater may be in excess of 500 ft, and the water quality may be poor. Shallow alluvium may be somewhat finer grained than at other settings, and the surface appears to be relatively stable and devoid of major incision by existing drainages. Although each of these characteristics needs to be investigated by further work, the most critical unanswered question is the thickness of alluvial fill. Available gravity data, including recent work by The University of Texas at El Paso, indicates that 100 ft or more of alluvial fill may be present in the area. Other areas may be present that are of equal or similar merit, but the preliminary analysis and available information suggest that the Yucca Mesa location apparently has the most favorable characteristics of those general siting areas identified currently. Smaller potential siting areas, generally about 400 to 800 acres in size, also may exist locally throughout the region where alluvial fill may be of sufficient thickness and drainage characteristics may be appropriate. These smaller potential siting areas would require additional site-specific evaluation of surface drainage characteristics before drill testing could be recommended. Any potential siting area is unique and would require site-specific evaluation activities to assess its suitability for characterization.Bureau of Economic Geolog

A comparative study of WASP-67b and HAT-P-38b from WFC3 data

Atmospheric temperature and planetary gravity are thought to be the main parameters affecting cloud formation in giant exoplanet atmospheres. Recent attempts to understand cloud formation have explored wide regions of the equilibrium temperature-gravity parameter space. In this study, we instead compare the case of two giant planets with nearly identical equilibrium temperature ($T_\mathrm{eq}$ $\sim 1050 \, \mathrm{K}$) and gravity ($g \sim 10 \, \mathrm{m \, s}^{-1})$. During $HST$ Cycle 23, we collected WFC3/G141 observations of the two planets, WASP-67 b and HAT-P-38 b. HAT-P-38 b, with mass 0.42 M$_\mathrm{J}$ and radius 1.4 $R_\mathrm{J}$, exhibits a relatively clear atmosphere with a clear detection of water. We refine the orbital period of this planet with new observations, obtaining $P = 4.6403294 \pm 0.0000055 \, \mathrm{d}$. WASP-67 b, with mass 0.27 M$_\mathrm{J}$ and radius 0.83 $R_\mathrm{J}$, shows a more muted water absorption feature than that of HAT-P-38 b, indicating either a higher cloud deck in the atmosphere or a more metal-rich composition. The difference in the spectra supports the hypothesis that giant exoplanet atmospheres carry traces of their formation history. Future observations in the visible and mid-infrared are needed to probe the aerosol properties and constrain the evolutionary scenario of these planets.Comment: 16 pages, 17 figures, 8 tables, accepted for publication in The Astronomical Journa