Heme regulation in mouse mammary carcinoma and liver of tumor bearing mice-I. Effect of allyl-isopropylacetamide and veronal on δ -aminolevulinate synthetase, cytochrome P-450 and cytochrome oxidase

1. 1. Basal levels and allyl-isopropylacetamide (AIA) or veronal induced levels of δ-aminolevulinate synthetase (ALA-S), cytochrome P-450 (cyt P-450) and cytochrome oxidase were determined in tumor (T) and liver of both normal mice (NM) and T bearing mice (TBM). 2. 2. Basal levels of ALA-S were nearly the same in either source. The amount of cyt P-450 was lower in TBM liver than in NM liver, and no detectable in T. While the basal activity of cytochrome oxidase in TBM liver and T were higher than those of NM liver. 3. 3. In AIA intoxicated animals there was a lower induction of ALA-S in liver of TBM than in NM liver. There was no induction in T ALA-S. The loss of cyt P-450 was less in TBM liver when compared with NM liver. 4. 4. The induction level of cyt P-450 after veronal administration was nearly the same in liver of both TBM and NM. 5. 5. We conclude that lower induction of liver ALA-S activity in TBM liver is due to correspondingly lower drug metabolism ability of TBM liver. Otherwise our results suggest that the control mechanism operating in T and probably in its original tissue are different from those described for normal liver. © 1990.Fil:Del C. Batlle, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Dysregulation of Arginase Isoenzymes in FL-HCC: Investigating the Impact of Nonspecific Arginase-Isoform Antibodies on the Market

In this project, we investigated the expression of the isoenzymes Arginase 1 (ARG1) and Arginase 2 (ARG2) in fibrolamellar hepatocellular carcinoma (FL-HCC) tissue samples. Previous proteomics data had predicted ARG2 to be up-regulated in FL-HCC without clear indication of dysregulation in ARG1. We utilized western blot analysis to determine protein expression by comparing five FL-HCC patient samples to three normal liver tissue samples. During the analysis, we discovered the non-specificity of several commercially bought ARG2 antibodies. This led to the design and execution of various experiments aimed at troubleshooting and identifying a commercially available ARG2 antibody that is specific for the ARG2 isotype. Once the ARG2 isotype-specific antibody was identified, it was used for western blot analysis. Our data concluded that ARG2 expression is up-regulated in FL-HCC. In addition, our data shows that ARG1 expression is sample-specific, pointing to possible stage-specific dysregulation of ARG1 in FL-HCC tumor samples. Overall, our project demonstrates the importance of verifying isoform-specific antibodies while determining the expression of Arginase isoforms in tissue samples. Our findings have important implications for FL-HCC research, as they suggest that targeting ARG2 may be a promising therapeutic strategy. Additionally, our study highlights the need for careful validation of isoform-specific antibodies in cancer research, which can improve the accuracy and reliability of experimental results

Cytochrome P450 inhibition potential of new psychoactive substances of the tryptamine class

New psychoactive substances (NPS) are not tested for their cytochrome P450 (CYP) inhibition potential before consumption. Therefore, this potential was explored for tryptamine-derived NPS (TDNPS) including alpha-methyl tryptamines (AMTs), dimethyl tryptamines (DMTs), diallyl tryptamines (DALTs), and diisopropyl tryptamines (DiPTs) using test substrates preferred by the Food and Drug Administration in a cocktail assay. All tested TDNPS with the exception of DMT inhibited CYP2D6 activity with IC50 values below 100 μM. DALTs inhibited CYP2D6 activity similar to paroxetine and quinidine and CYP1A2 activity comparable to fluvoxamine. 5-Methoxy-N,N-diallyltryptamine reduced in vivo the caffeine metabolism in rats consistent with in vitro results. Five of the AMTs also inhibited CYP1A2 activity comparable to amiodarone. AMT and 6-F-AMT inhibited CYP2A6 activity in the range of the test inhibitor tranylcypromine. CYP2B6 activity was inhibited by 19 tryptamines, but weakly compared to efavirenz. CYP2C8 activity was inhibited by five of the tested TDNPS and three showed values comparable to trimethoprim and gemfibrozil. Six tryptamines inhibited CYP2C9 and seven CYP2C19 activities comparable to fluconazole and chloramphenicol, respectively. Nineteen compounds showed inhibition of CYP2E1 and 18 of CYP3A activity, respectively. These results showed that the CYP inhibition by TDNPS might be clinically relevant, but clinical studies are needed to explore this further

The Effect of Vitamin C on HeLa Cell Proliferation

In this study, we investigated the impact of vitamin C on cervical cancer cells at varying concentrations. After adding vitamin C reagent to plated HeLa cells, we performed cytotoxicity assays to measure cell viability. We hypothesized that higher concentrations of vitamin C would lead to lower cell viability, as vitamin C is predicted to cause cell death in cancer cells. Our results indicated that higher concentrations of vitamin C do not necessarily correlate with lower cell viability of cervical cancer cells

Influence of deformation axis onto the length free path of screw dislocations in pure fcc materials

In this paper the influence of crystal's deformation axis orientation on formation of long, strong dislocation junctions which can be barriers that limit the shear zone has been studied. The probability of strong junctions formation has been obtained on the basis of interdislocation contact interactions model. The length of free path of screw dislocations has been defined for different orientations of crystal's deformation axis

Hydrogeology, Hydrogeochemistry, and Spoil Settlement at a Large Mine-Spoil Area in Eastern Kentucky: Star Fire Tract

An applied research program at the Star Fire surface mine in eastern Kentucky, owned and operated by Cypress-AMAX Coal Co., defined spoil characteristics to develop and monitor water resources, which will help identify a reliable water supply for future property development. Water stored in the mine spoil may provide a usable ground-water supply, and the spoil could also be engineered to provide base flow to surfacewater reservoirs. Ground-water recharge enters the spoil by way of sinking streams, ground-water flow from bedrock in contact with the mine spoil, and a specially designed infiltration basin. Ground water discharges predominantly from springs and seeps along the northwestern outslope of the spoil. A conceptual model of ground-water flow, based on data from monitoring wells, discharge from springs and ponds, dye tracing, hydraulic gradients, and field reconnaissance, indicates that ground water moves slowly in the spoil interior, where it must flow down into the valley fills before discharging out of the spoil. Two saturated zones have been established: the first in the spoil interior, and the second in the valley fills that surround the main spoil body at lower elevations. The saturated zone in the valley fills contains fresher water than the zone in the spoil interior and exhibits more water-level fluctuation because of efficient recharge pathways along the spoil’s periphery at the spoil-highwall contact. The average saturated thickness of the valley fill areas (30.1 ft) is approximately twice the average saturated thickness found in the spoil’s interior (15.4 ft). Spatial water-quality variations are consistent with those predicted in the proposed flow system. Based on an estimated average saturated thickness of 21 ft for the entire site, the saturated spoil stores 4,200 acre-ft (1.4 billion gallons) of water. Hydraulic-conductivity (K) values derived from slug tests range from 2.0 × 10-6 to more than 2.9 × 10-5 ft/sec, and are consistent with hydraulic-conductivity data for other spoil areas where similar mining methods are used. Water samples taken from wells and springs indicate that the ground water is a calcium-magnesium-sulfate type, differing mainly in the total concentration of these constituents at various locations. Mineral saturation indices calculated using the geochemical model PHREEQE indicate that most of the ground water is near equilibrium with gypsum. Nearly all the water samples had pH measurements in a favorable range between 6.0 and 7.0, indicating that the spoil does not produce highly acidic water. Measurements of vertical displacement around the monitoring-well surface casings indicate that differential settlement is occurring within the mine spoil. The most rapid settlement occurs in the most recently placed spoil near the active mining pit

Hydrogeology and Ground-Water Monitoring of Coal-Ash Disposal Sites in a Karst Terrane near Burnside, South-Central Kentucky

The effects of two coal-ash disposal facilities on ground-water quality at the John Sherman Cooper Power Plant, located in a karst region of south-central Kentucky, were evaluated using dye traces in springs. Springs were used for monitoring rather than wells, because in a karst terrane wells are unlikely to intercept individual conduits. A closed-out ash pond located over a conduit-flow system discharges to three springs in the upper Salem and Warsaw Formations along Lake Cumberland. Water discharging from these downgradient springs is similar to springs unaffected by ash-disposal facilities and is a calcium-bicarbonate type. No constituent concentrations found in this flow system exceeded maximum contaminant levels (MCL’s) or secondary maximum contaminant levels (SMCL’s) defined by the U.S. Environmental Protection Agency. An active ash pond is situated over another conduit-flow system that discharges to springs in the lower St. Louis Limestone. Water discharging from these downgradient springs is intermediate between the calciumbicarbonate type of the unaffected springs and the calcium-sulfate type of the active ash pond. No constituent concentrations found in this flow system exceeded MCL’s or SMCL’s. A third flow system associated with a coal stockpile adjacent to the plant is delineated by springs in the St. Louis Limestone and the Salem and Warsaw Formations that discharge calcium-sulfate type water. Chromium and cadmium concentrations exceeded MCL’s in at least one sample from this flow system. Iron, manganese, sulfate, and total dissolved solid concentrations exceeded SMCL’s in at least one sample. The closed-out ash pond appears to have no adverse impact on the water quality, nor does the active ash pond. In general, the coal stockpile has a more adverse impact on ground-water quality in the study area than the ash-disposal facilities

Hydrogeologic Investigations of Pavement Subsidence in the Cumberland Gap Tunnel

Cumberland Gap Tunnel was constructed under Cumberland Gap National Historical Park in 1996 to improve transportation on a segment of U.S. 25E, connecting Kentucky and Tennessee and restoring Cumberland Gap to its historical appearance. The concrete pavement in the tunnel started to subside in 2001. Ground penetrating radar surveys revealed voids in many areas of the limestone roadbed aggregate beneath the pavement. To investigate possible hydrogeologic processes that may have caused favorable conditions for voids to form in the aggregate, we studied geology, groundwater flow, and groundwater chemistry in the tunnel using a variety of methods, including bore drilling, packer test, dye tracing, groundwater- and surface-flow monitoring, water-chemistry modeling, and an aggregate dissolution experiment. The study revealed that the aggregate receives a large volume of groundwater from much of the bedrock invert, but the flow velocity is too slow to transport small particles out of the aggregate. Calcite saturation indices calculated from water-chemistry data suggest that the groundwater was capable of continuously dissolving calcite, the primary mineral in the limestone aggregate. Water samples taken during different flow conditions indicate that groundwater under low-flow conditions. The dissolution experiment showed that all the limestone aggregate placed beneath the roadbed and in contact with groundwater lost mass; the highest mass loss was 3.4 percent during a 178-day period. The experiment also suggested that water with higher calcite-dissolving potential removed limestone mass quicker than water with low calcite-dissolving potential. We recommend that the limestone aggregate be replaced with noncarbonate aggregate, such as granite, to prevent dissolution and future road subsidence

Can R CrB stars form from the merger of two helium white dwarfs?

Due to orbital decay by gravitational-wave radiation, some close-binary helium white dwarfs are expected to merge within a Hubble time. The immediate merger products are believed to be helium-rich sdO stars, essentially helium main-sequence stars. We present new evolution calculations for these post-merger stars beyond the core helium-burning phase. The most massive He-sdO's develop a strong helium-burning shell and evolve to become helium-rich giants. We include nucleosynthesis calculations following the merger of $0.4 \rm M_{\odot}$ helium white-dwarf pairs with metallicities $Z = 0.0001, 0.004, 0.008$ and 0.02. The surface chemistries of the resulting giants are in partial agreement with the observed abundances of R Coronae Borealis and extreme helium stars. Such stars might represent a third, albeit rare, evolution channel for the latter, in addition to the CO+He white dwarf merger and the very-late thermal pulse channels proposed previously. We confirm a recent suggestion that lithium seen in R\,CrB stars could form naturally during the hot phase of a merger in the presence of \iso{3}{He} from the donor white dwarf.Comment: 5 pages, 3 figures. Accepted for publication in MNRAS letter