synthesis-and-microdiffraction-at-extreme-pressures-and-temperatures

Synthesis and Microdiffraction at Extreme Pressures and Temperatures

High pressure compounds and polymorphs are investigated for a broad range of purposes such as determine structures and processes of deep planetary ...

University of Nevada, Las Vegas

Oxidative stress is involved in the sarcopenia of aging muscles. On the grounds that ventilatory muscles are permanently active, and their activity may even increase with aging, we hypothesized that the levels of oxidative stress would probably be increased in the external intercostals of elderly healthy individuals. We conducted a case-control study in which reactive carbonyl groups, malondialdehyde-protein adducts, 3-nitrotyrosine immunoreactivity, Mn-superoxide dismutase (Mn-SOD), and catalase were detected using immunoblotting in external intercostals and quadriceps (open muscle biopsies) obtained from 12 healthy elderly and 12 young individuals of both sexes. In elderly subjects, reactive carbonyls, malondialdehyde-protein adducts, 3-nitrotyrosine, Mn-SOD, and catalase were significantly greater in the external intercostals than in the young controls. A post hoc analysis, in which men and women from both groups were analyzed separately, revealed that the external intercostals of elderly women, but not those of elderly men, showed significantly increased levels of reactive carbonyls, malondialdehyde-protein adducts, 3-nitrotyrosine, and Mn-SOD compared to those of control females. This study suggests that differences in muscle activity might explain the differential pattern of oxidative stress observed in human respiratory and limb muscles with aging as well as the likely existence of a sex-related regulation of this phenomenon in these muscles.

Aging, sex differences, and oxidative stress in human respiratory and limb muscles.

Cyclooxygenase-1 (COX-1) is overexpressed in sinusoidal endothelial cells (SEC) of cirrhotic rat livers, and through an enhanced production of vasoconstrictor prostanoids contributes to increase intrahepatic resistance. Our study was aimed at investigating the role of enhanced AA bioavailability modulating the hepatic vascular tone of cirrhotic livers and identifying which prostanoid is involved.

Enhanced vasoconstrictor prostanoid production by sinusoidal endothelial cells increases portal perfusion pressure in cirrhotic rat livers.

Tyrrellite, a naturally occurring Co-Ni-Cu selenide, has been studied by single-crystal X-ray diffraction. It possesses the normal spinel-type structure, with Cu occupying the tetrahedral site and (Co+Ni) the octahedral site. The average Cu-Se distance of 2.3688 (2) A is close to that of 2.3703 (8) A in CuCr(2)Se(4), whereas the average (Co+Ni)-Se distance of 2.3840 (1) A appears to be slightly shorter than most octahedral Co-Se or Ni-Se distances ( approximately 2.40-2.50 A) in other selenides. The refined structure provides a basis for a redefinition of the ideal chemical formula of tyrrellite, which should be Cu(Co,Ni)(2)Se(4), rather than the previously suggested (Cu,Co,Ni)(3)Se(4).

Tyrrellite, Cu(Co0.68Ni0.32)2Se4, isostructural with spinel.

Increased hepatic vascular resistance in cirrhosis is in part due to reduced nitric oxide (NO) bioavailability. This is related to insufficient NO synthesis from endothelial nitric oxide synthase and to enhanced NO scavenging by superoxide radicals (O(2)(-)). Nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase is an important source of O(2)(-) that increases vascular tone in different cardiovascular disorders. Thus, our aims were to study the molecular and biochemical state of NADPH-oxidase in cirrhotic livers and to investigate its possible role in modulating hepatic vascular tone in cirrhosis.

Evidence against a role for NADPH oxidase modulating hepatic vascular tone in cirrhosis.

In cirrhotic livers, decreased nitric oxide (NO) bioavailability is a major factor increasing intrahepatic vascular tone. In several vascular disorders, an increase in superoxide (O(2) (-)) has been shown to contribute to reduced NO bioavailability through its reaction with NO to form peroxynitrite. This study was aimed to test the hypothesis that, in cirrhotic livers, increased O(2) (-), by reacting with NO, reduces NO bioavailability. In control and cirrhotic rat livers, NO bioavailability was evaluated by the measurement of cyclic guanosine monophosphate in liver tissue and by 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM-DA) fluorescence in isolated sinusoidal endothelial cells (SEC); the O(2) (-) content was determined by dihydroethidium staining in fresh liver sections. In addition, the role of endothelial nitric oxide synthase (eNOS), xanthine oxidase (XO), and cyclooxygenase (COX) as possible sources of O(2) (-) and the role of superoxide dismutase (SOD) enzymatic activity as an O(2) (-) scavenger were determined in liver homogenates. Protein-nitrotyrosination, a marker of the NO-O(2) (-) reaction, was evaluated in liver homogenates. Furthermore, in control SEC and bovine aortic endothelial cells, NO modulation by O(2) (-) was evaluated. Cirrhotic livers exhibited increased O(2) (-) levels. This was due, at least in part, to increased production by COX and XO but not eNOS and to reduced scavenging by SOD. Increased O(2) (-) was associated with a significant reduction in NO bioavailability and increased nitrotyrosinated proteins. In endothelial cells, an inverse relationship between O(2) (-) levels and NO bioavailability was observed. Conclusion: Our data show that oxidative stress may contribute to reduced NO bioavailability in cirrhotic livers, supporting the evaluation of O(2) (-) reduction as a potential mechanism to restore NO content.

Increased oxidative stress in cirrhotic rat livers: A potential mechanism contributing to reduced nitric oxide bioavailability.

Increased superoxide in cirrhotic livers, by reducing nitric oxide bioavailability, contributes to increase intrahepatic vascular resistance to portal blood flow and as a consequence portal pressure. We aimed to evaluate whether a strategy directed to reduce superoxide using tempol, a small membrane permeable SOD-mimetic, is able to modulate intrahepatic nitric oxide content and reduce portal pressure in cirrhotic rats.

Tempol administration, a superoxide dismutase mimetic, reduces hepatic vascular resistance and portal pressure in cirrhotic rats.

Phases of the iron-oxygen binary system are significant to most scientific disciplines, directly affecting planetary evolution, life, and technology. Iron oxides have unique electronic properties and strongly interact with the environment, particularly through redox reactions. The iron-oxygen phase diagram therefore has been among the most thoroughly investigated, yet it still holds striking findings. Here, we report the discovery of an iron oxide with formula Fe(4)O(5), synthesized at high pressure and temperature. The previously undescribed phase, stable from 5 to at least 30 GPa, is recoverable to ambient conditions. First-principles calculations confirm that the iron oxide here described is energetically more stable than FeO + Fe(3)O(4) at pressure greater than 10 GPa. The calculated lattice constants, equation of states, and atomic coordinates are in excellent agreement with experimental data, confirming the synthesis of Fe(4)O(5). Given the conditions of stability and its composition, Fe(4)O(5) is a plausible accessory mineral of the Earth's upper mantle. The phase has strong ferrimagnetic character comparable to magnetite. The ability to synthesize the material at accessible conditions and recover it at ambient conditions, along with its physical properties, suggests a potential interest in Fe(4)O(5) for technological applications.

Discovery of the recoverable high-pressure iron oxide Fe4O5.

Peroxisome proliferator-activated receptor Î± (PPARÎ±) is a transcription factor activated by ligands that regulates genes related to vascular tone, oxidative stress, and fibrogenesis, pathways implicated in the development of cirrhosis and portal hypertension. This study aims at evaluating the effects of PPARÎ± activation with fenofibrate on hepatic and systemic hemodynamics, hepatic endothelial dysfunction, and hepatic fibrosis in CCl(4)-cirrhotic rats.

PPARÎ± activation improves endothelial dysfunction and reduces fibrosis and portal pressure in cirrhotic rats.

Angiogenesis, the process by which new blood vessels arise from preexisting ones, is critical for embryonic development and is an integral part of many disease processes. Recent studies have provided detailed information on how angiogenic sprouts initiate, elongate, and branch, but less is known about how these processes cease. Here, we show that S1PR1, a receptor for the blood-borne bioactive lipid sphingosine-1-phosphate (S1P), is critical for inhibition of angiogenesis and acquisition of vascular stability. Loss of S1PR1 leads to increased endothelial cell sprouting and the formation of ectopic vessel branches. Conversely, S1PR1 signaling inhibits angiogenic sprouting and enhances cell-to-cell adhesion. This correlates with inhibition ofÂ vascular endothelial growth factor-A (VEGF-A)-induced signaling and stabilization of vascular endothelial (VE)-cadherin localization at endothelial junctions. Our data suggest that S1PR1 signaling acts as a vascular-intrinsic stabilization mechanism, protecting developing blood vessels against aberrant angiogenic responses.

Article	Year
Aging, sex differences, and oxidative stress in human respiratory and limb muscles. Free radical biology & medicine\| PubMed ID: 16895800	2006
Enhanced vasoconstrictor prostanoid production by sinusoidal endothelial cells increases portal perfusion pressure in cirrhotic rat livers. Journal of hepatology\| PubMed ID: 17459512	2007
Tyrrellite, Cu(Co0.68Ni0.32)2Se4, isostructural with spinel. Acta crystallographica. Section C, Crystal structure communications\| PubMed ID: 17675677	2007
Evidence against a role for NADPH oxidase modulating hepatic vascular tone in cirrhosis. Gastroenterology\| PubMed ID: 17854599	2007
Increased oxidative stress in cirrhotic rat livers: A potential mechanism contributing to reduced nitric oxide bioavailability. Hepatology (Baltimore, Md.)\| PubMed ID: 18273863	2008
Tempol administration, a superoxide dismutase mimetic, reduces hepatic vascular resistance and portal pressure in cirrhotic rats. Journal of hepatology\| PubMed ID: 21159403	2011
Discovery of the recoverable high-pressure iron oxide Fe4O5. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 21969537	2011
PPARÎ± activation improves endothelial dysfunction and reduces fibrosis and portal pressure in cirrhotic rats. Journal of hepatology\| PubMed ID: 22245887	2012
The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2. Developmental cell\| PubMed ID: 22975327	2012

Barbara Lavina

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