314 research outputs found
Replenishment of selenium deficient rats with selenium results in redistribution of the selenocysteine tRNA population in a tissue specific manner
AbstractWe reported previously that the selenium status of rats influences both the steady-state levels and distributions of two selenocysteine tRNA isoacceptors and that these isoacceptors differ by a single methyl group attached to the ribosyl moiety at position 34. In this study, we demonstrate that repletion of selenium-deficient rats results in a gradual, tissue-dependent shift in the distribution of these isoacceptors. Rats fed a selenium-deficient diet possess a greater abundance of the species unmethylated on the ribosyl moiety at position 34 compared to the form methylated at this position. A redistribution of the Sec–tRNA isoacceptors occurred in tissues of selenium-supplemented rats whereby the unmethylated form gradually shifted toward the methylated form. This was true in each of four tissues examined, muscle, kidney, liver and heart, although the rate of redistribution was tissue-specific. Muscle manifested a predominance of two minor serine isoacceptors under conditions of extreme selenium-deficiency which also appeared to respond to selenium. Ribosomal binding studies revealed that one of the two additional isoacceptors decodes the serine codeword, AGU, and the second decodes the serine codeword, UCU. Interestingly, muscle and heart were the slower tissues to return to a `selenium adequate' tRNA distribution pattern
Safety and Efficacy of Long-Term Co-Administration of Fenofibrate and Ezetimibe in Patients With Mixed Hyperlipidemia
ObjectivesThis study sought to determine the long-term safety and efficacy of co-administered fenofibrate (FENO) and ezetimibe (EZE) in patients with mixed hyperlipidemia.BackgroundBoth EZE and FENO offer complementary benefits to the lipid profile of patients with mixed hyperlipidemia.MethodsAfter completing the 12-week randomized, double-blind base study that compared EZE 10 mg, FENO 160 mg, FENO 160 mg plus EZE 10 mg, and placebo in patients with mixed hyperlipidemia, patients continued into a double-blind, 48-week extension phase. Those patients in the FENO plus EZE and FENO groups continued on their respective base study treatment, and patients in the EZE and placebo groups were switched to FENO plus EZE and FENO, respectively.ResultsOf the 587 patients who completed the base study, 576 continued into the extension study (n = 340 in FENO plus EZE and n = 236 in FENO). The FENO plus EZE produced significantly greater reductions in low-density lipoprotein-cholesterol compared with FENO (−22% vs. −9%, respectively; p < 0.001). There were also significantly greater improvements in triglycerides, high-density lipoprotein cholesterol (HDL-C), total cholesterol, non–HDL-C, and apolipoprotein B with FENO plus EZE compared with FENO. Changes in apolipoprotein A-I and high-sensitivity C-reactive protein were similar between groups. Overall, FENO plus EZE was well tolerated during the extension study. The proportion of patients with consecutive elevations of alanine aminotransferase/aspartate aminotransferase ≥3 times upper limit of normal were similar between the FENO plus EZE (1.2%) and FENO (1.7%) groups. No cases of creatine phosphokinase elevations ≥10 times upper limit of normal or myopathy were observed in either group.ConclusionsLong-term, 48-week co-administration of FENO plus EZE was well tolerated and more efficacious than FENO in patients with mixed hyperlipidemia
The Energetic Potential for Undiscovered Manganese Metabolisms in Nature
Microorganisms are found in nearly every surface and near-surface environment, where they gain energy by catalyzing reactions among a wide variety of chemical compounds. The discovery of new catabolic strategies and microbial habitats can therefore be guided by determining which redox reactions can supply energy under environmentally-relevant conditions. In this study, we have explored the thermodynamic potential of redox reactions involving manganese, one of the most abundant transition metals in the Earth’s crust. In particular, we have assessed the Gibbs energies of comproportionation and disproportionation reactions involving Mn2+ and several Mn-bearing oxide and oxyhydroxide minerals containing Mn in the +II, +III, and +IV oxidation states as a function of temperature (0–100°C) and pH (1–13). In addition, we also calculated the energetic potential of Mn2+ oxidation coupled to O2, NO2–, NO3–, and FeOOH. Results show that these reactions—none of which, except O2 + Mn2+, are known catabolisms—can provide energy to microorganisms, particularly at higher pH values and temperatures. Comproportionation between Mn2+ and pyrolusite, for example, can yield 10 s of kJ (mol Mn)–1. Disproportionation of Mn3+ can yield more than 100 kJ (mol Mn)–1 at conditions relevant to natural settings such as sediments, ferromanganese nodules and crusts, bioreactors and suboxic portions of the water column. Of the Mn2+ oxidation reactions, the one with nitrite as the electron acceptor is most energy yielding under most combinations of pH and temperature. We posit that several Mn redox reactions represent heretofore unknown microbial metabolisms
Keith County, Nebraska, Map Series
KEITH COUNTY--LIST OF MAPS AND THEIR AUTHORS
Topography--U. S. Geological Survey
Index of 7.5\u27 Topographic Quadrangles and Township Boundaries--R. F. Diffendal, Jr.
Generalized Soils Map--M. Kuzila and J. Culver
Approximate Loess Thickness--R. F. Diffendal, Jr.
Bedrock Geologic Map--R. F. Diffendal, Jr.
Volcanic Ash Localities--R. F. Diffendal, Jr.
Ogallala Vertebrate Faunal Sites--R. F. Diffendal, Jr.
Ogallala Group Outcrops--R. F. Diffendal, Jr.
White River Group Outcrops--R. F. Diffendal, Jr.
Conservation and Survey Division Test Hole Locations--R. F. Diffendal, Jr.
Oil and/or Gas Test Hole Locations--R. F. Diffendal, Jr.
Mineral Resources Localities--R. F. Diffendal, Jr.
Locations of Registered Irrigation Wells--R. F. Diffendal, Jr.
Configuration of Top of Bedrock--R. F. Diffendal, Jr.
Configuration of Top of White River Group (= Brule Fm.)--R. F. Diffendal, Jr.
Configuration of Top of Cretaceous--H. M. DeGraw
Configuration of Top of Niobrara Fm.--H. M. DeGraw
Configuration of Base of Greenhorn Limestone--H. M. DeGraw
Configuration of Top of Permian System--R. R. Burchett
Structural Contours on Top of Stone Corral--R. R. Burchett
Structural Contours on Top of Pennsylvanian System--R. R. Burchett
Depth to Precambrian Surface--M. P. Carlson
Configuration of Top of Precambrian--R. R. Burchett and M. P. Carlson
Geothermal Projected Temperatures on Top of Dakota Group--D. Eversoll and W. Gosnold
Bouguer Gravity Anomaly Map--R. R. Burchett and T. Eversol
Keith County, Nebraska, Map Series
KEITH COUNTY--LIST OF MAPS AND THEIR AUTHORS
Topography--U. S. Geological Survey
Index of 7.5\u27 Topographic Quadrangles and Township Boundaries--R. F. Diffendal, Jr.
Generalized Soils Map--M. Kuzila and J. Culver
Approximate Loess Thickness--R. F. Diffendal, Jr.
Bedrock Geologic Map--R. F. Diffendal, Jr.
Volcanic Ash Localities--R. F. Diffendal, Jr.
Ogallala Vertebrate Faunal Sites--R. F. Diffendal, Jr.
Ogallala Group Outcrops--R. F. Diffendal, Jr.
White River Group Outcrops--R. F. Diffendal, Jr.
Conservation and Survey Division Test Hole Locations--R. F. Diffendal, Jr.
Oil and/or Gas Test Hole Locations--R. F. Diffendal, Jr.
Mineral Resources Localities--R. F. Diffendal, Jr.
Locations of Registered Irrigation Wells--R. F. Diffendal, Jr.
Configuration of Top of Bedrock--R. F. Diffendal, Jr.
Configuration of Top of White River Group (= Brule Fm.)--R. F. Diffendal, Jr.
Configuration of Top of Cretaceous--H. M. DeGraw
Configuration of Top of Niobrara Fm.--H. M. DeGraw
Configuration of Base of Greenhorn Limestone--H. M. DeGraw
Configuration of Top of Permian System--R. R. Burchett
Structural Contours on Top of Stone Corral--R. R. Burchett
Structural Contours on Top of Pennsylvanian System--R. R. Burchett
Depth to Precambrian Surface--M. P. Carlson
Configuration of Top of Precambrian--R. R. Burchett and M. P. Carlson
Geothermal Projected Temperatures on Top of Dakota Group--D. Eversoll and W. Gosnold
Bouguer Gravity Anomaly Map--R. R. Burchett and T. Eversol
Contract Renegotiation and Rent Re-distribution: Who Gets Raked Over the Coals?
Policy shocks affect the rent distribution in long-term contracts, which can lead to such contracts being renegotiated. We seek an understanding of what aspects of contract design, in the face of a substantial policy shock, affect the propensity to renegotiate. We test our hypotheses using data on U.S. coal contracts after the policy shock of the 1990 Clean Air Act Amendments. Contracts are divided into two categories, those that were renegotiated following the shock and those that were not. Characteristics of the contract are used to explain whether or not the contract was ultimately renegotiated. Results provide guidance on rent re-distribution and contract renegotiation more generally and are applicable to contemporary policy issues such as climate change legislatio
Effect of combination glipizide GITS/metformin on fibrinolytic and metabolic parameters in poorly controlled type 2 diabetic subjects
WSTĘP. Wyniki badań epidemiologicznych wskazują, że podwyższone
stężenie inhibitora aktywatora plazminogenu 1 (PAI-1) w surowicy krwi może być
wskaźnikiem lub predyktorem przyspieszonego rozwoju choroby wieńcowej u chorych
na cukrzycę typu 2. Celem pracy było określenie, czy poprawa wyrównania metabolicznego,
niezależnie od rodzaju stosowanych leków doustnych, wpływa na stężenie PAI-1 u
chorych ze znaczną hiperglikemią.
MATERIAŁ I METODY. Do badania zakwalifikowano 91 chorych. Po
okresie 4 tygodni, w którym pacjenci nie przyjmowali żadnych leków, chorych losowo
przydzielono do grupy leczonej glipizydem GITS (w dawce maksymalnej 20 mg, n =
46) lub grupy otrzymującej metforminę (maksymalnie 2550 mg, n = 45) w monoterapii.
Po okresie monoterapii wprowadzono leczenie skojarzone, dodając drugi lek do preparatu
już stosowanego. U wszystkich pacjentów przed i po randomizacji oraz podczas badania
oznaczono glikemię (na czczo i po posiłku), stężenie HbA1c, fruktozaminy oraz PAI-1. U części chorych zmierzono również wątrobową produkcję glukozy (HGO, hepatic glucose output) oraz oznaczono rozkład brzusznej tkanki tłuszczowej.
WYNIKI. Wyrównanie glikemii na początku badania było niezadowalające
(średnie stężenie HbA1c 10,4 ± 0,2% w grupie glipizydu GITS; 10,0 ± 0,2% w grupie metforminy), ale poprawiło się istotnie w obu grupach, stosujących monoterapię
oraz w wyniku leczenia skojarzonego (p < 0,0001 vs. wyniki wyjściowe), co oceniono
na podstawie badania tolerancji posiłku, stężenia fruktozaminy oraz HGO. Masa
ciała oraz rozkład brzusznej tkanki tłuszczowej nie zmieniły się istotnie w żadnej
z grup. Stężenie PAI-1 było wyjątkowo wysokie (5-10-krotnie wyższe od wartości
prawidłowych) na początku badania (202 ± 12 ng/ml w grupie glipizydu GITS; 201
± 13 ng/ml w grupie metforminy), ale istotnie obniżyło się podczas badania, w
sposób porównywalny w monoterapii w obu grupach. Podczas leczenia skojarzonego
stężenie to uległo dalszemu obniżeniu.
WNIOSKI. W przypadkach nasilonej hiperglikemii stężenie PAI-1
jest również znacznie podwyższone. Obniżenie hiperglikemii za pomocą leku nasilającego
wydzielanie insuliny, glipizydu GITS lub metforminy, stosowanych w monoterapii,
w porównywalny sposób powoduje obniżenie stężenia PAI-1.INTRODUCTION. Epidemiological studies have implicated
increased plasminogen-activated inhibitor 1
(PAI-1) as a marker or predictor of accelerated coronary
atherosclerotic disease in type 2 diabetes. We
sought to determine whether metabolic control, independent
of its oral mode of implementation, affects
PAI-1 in patients with marked hyperglycemia.
MATERIAL AND METHODS. A total of 91 subjects were
screened, subjected to a 4-week drug washout, and
randomized to daily treatment with glipizide GITS
(maximum 20 mg, n = 46) or metformin (maximum
2,550 mg, n = 45) as monotherapy. After monotherapy,
combination therapy was initiated by adding
the second agent to the regimen. Plasma glucose
(fasting and postprandial), HbA1c, fructosamine, and
PAI-1 were assayed before and after randomization
and sequentially thereafter in all subjects; hepatic
glucose output (HGO) and abdominal fat distribution
were each measured in a subset of subjects.
RESULTS. Glycemic control was markedly impaired
at baseline (mean HbA1c 10.4 ± 0.2% glipizide GITS;
10.0 ± 0.2% metformin) but improved comparably
with each agent as monotherapy and in combination
(P < 0.0001 vs. baseline), as assessed with meal
tolerance studies, fructosamine values, and HGO.
Body weight and abdominal fat distribution did not
change significantly in either group. PAI-1 concentrations
were extraordinarily high (5- to 10-fold more
than normal) at baseline (202 ± 12 ng/ml glipizide
GITS; 201 ± 13 ng/ml metformin) but declined comparably,
and significantly, after treatment with either
agent as monotherapy and decreased further with
combination therapy.
CONCLUSIONS. When hyperglycemia is profound,
increases in PAI-1 are also profound. Control of hyperglycemia
with either glipizide GITS, an insulin
secretagogue, or metformin as monotherapy comparably
ameliorates elevated PAI-1
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