Short-Term Supplementation of Sodium Nitrate vs. Sodium Chloride Increases Homoarginine Synthesis in Young Men Independent of Exercise

The aim of the study was to investigate the effects of short-term oral administration of inorganic nitrate (NaNO₃; n = 8) or placebo (NaCl; n = 9) (each 0.1 mmol/kg body weight/d for 9 days) on plasma amino acids, creatinine, and oxidative stress in healthy young men. At baseline, the plasma concentrations of amino acids did not differ between the groups. At the end of the study, the plasma concentrations of homoarginine (hArg; by 24%, p = 0.0001), citrulline and ornithine (Cit/Orn; by 16%, p = 0.015), and glutamine/glutamate (Gln/Glu; by 6%, p = 0.0003) were higher in the NaNO₃ group compared to the NaCl group. The plasma concentrations of sarcosine (Sarc; by 28%, p < 0.0001), tyrosine (by 14%, p = 0.0051), phenylalanine (by 8%, p = 0.0026), and tryptophan (by 8%, p = 0.0047) were lower in the NaNO₃ group compared to the NaCl group. These results suggest that nitrate administration affects amino-acid metabolism. The arginine/glycine amidinotransferase (AGAT) catalyzes two reactions: (1) the formation of l-homoarginine (hArg) and l-ornithine (Orn) from l-arginine (Arg) and l-lysine (Lys): Arg + Lys <−> hArg + Orn, with equilibrium constant K_harg; (2) the formation of guanidinoacetate (GAA) and Orn from Arg and glycine (Gly): Arg + Gly <−> GAA + Orn, with equilibrium constant K_gaa. The plasma K_gaa/K_hArg ratio was lower in the NaNO₃ group compared to the NaCl group (1.57 vs. 2.02, p = 0.0034). Our study suggests that supplementation of inorganic nitrate increases the AGAT-catalyzed synthesis of hArg and decreases the N-methyltransferase-catalyzed synthesis of GAA, the precursor of creatine. To our knowledge, this is the first study to demonstrate elevation of hArg synthesis by inorganic nitrate supplementation. Remarkably, an increase of 24% corresponds to the synthesis capacity of one kidney in healthy humans. Differences in the association between plasma concentrations of amino acids in the NaNO₃ and NaCl groups suggest changes in amino-acid homeostasis. Plasma concentrations of the oxidative stress marker malondialdehyde (MDA) did not change after supplementation of NaNO₃ or NaCl over the whole exercise time range. Plasma nitrite concentration turned out to be a more discriminant marker of NaNO₃ ingestion than plasma nitrate (area under the receiver operating characteristic curve: 0.951 vs. 0.866, p < 0.0001 each).     

Photochemische Reaktionen von Pyrazolidon-(3)-betainen. IV. Photooxydation von Pyrazolidon-(3)-azomethiniminen

Photochemical Reactions of 3-Pyrazolidone Betains. IV. Photooxidation of 3-Pyrazolidone Azomethinimines Azomethinimines 1 , easily obtainable from 3-pyrazolidone and aldehydes, on dyesensitized photooxidation in methanol as a solvent undergo decomposition to nitrogen, methyl β-methoxypropionate 3 , methyl acrylate 4 and the corresponding aldehyde 2 . The formation of these products is interpreted by formation and decomposition of a cyclic peroxide 5 , produced by a 1,3-dipolar cycloaddition reaction between 1 and singlet oxygen. The photooxidation of 1 in acetonitrile produces: nitrogen, carbon dioxide, ethylene, β-propiolactone 9 , and the corresponding aldehyde 2 . The dye-sensitized photooxidation in methanol of the azomethinimines 16 , prepared from 3-pyrazolidone and ketones, gives the following products: nitrogen, methyl β-methoxypropionate 3 , methyl acrylate 4 , and the corresponding ketone, besides hydrazine and the corresponding α-methoxy-alkylhydroperoxides 17 and 21 . Key intermediate of the peroxide formation is the Criegee ozonization zwitterion which was trapped with acetaldehyde as an ozonide.     

The Novel Cardiac Myosin Activator Danicamtiv Improves Cardiac Systolic Function at the Expense of Diastolic Dysfunction In Vitro and In Vivo: Implications for Clinical Applications

Recent cardiotropic drug developments have focused on cardiac myofilaments. Danicamtiv, the second direct myosin activator, has achieved encouraging results in preclinical and clinical studies, thus implicating its potential applicability in the treatment of heart failure with reduced ejection fraction (HFrEF). Here, we analyzed the inotropic effects of danicamtiv in detail. To this end, changes in sarcomere length and intracellular Ca²⁺ levels were monitored in parallel, in enzymatically isolated canine cardiomyocytes, and detailed echocardiographic examinations were performed in anesthetized rats in the absence or presence of danicamtiv. The systolic and diastolic sarcomere lengths decreased; contraction and relaxation kinetics slowed down with increasing danicamtiv concentrations without changes in intracellular Ca²⁺ transients in vitro. Danicamtiv evoked remarkable increases in left ventricular ejection fraction and fractional shortening, also reflected by changes in systolic strain. Nevertheless, the systolic ejection time was significantly prolonged, the ratio of diastolic to systolic duration was reduced, and signs of diastolic dysfunction were also observed upon danicamtiv treatment in vivo. Taken together, danicamtiv improves cardiac systolic function, but it can also limit diastolic performance, especially at high drug concentrations.     

Whole-brain 3D MR fingerprinting brain imaging: clinical validation and feasibility to patients with meningioma

Magnetic Resonance Materials in Physics, Biology and Medicine - MR fingerprinting (MRF) is a MR technique that allows assessment of tissue relaxation times. The purpose of this study is to evaluate...     

Recent advances in evolutionary and bio-inspired adaptive robotics: Exploiting embodied dynamics

Applied Intelligence - This paper explores current developments in evolutionary and bio-inspired approaches to autonomous robotics, concentrating on research from our group at the University of...     

A proposal for future data organization in enterprise systems—an analysis of established database approaches

The digital transformation sets new requirements to all classes of enterprise systems in companies. ERP systems in particular, which represent the dominant class of enterprise systems, are struggling to meet the new requirements at all levels of the architecture. Therefore, there is an urgent need to reconsider the overall architecture of the systems and address the root of the related issues. Given that many restrictions ERP pose on their adaptability are related to the standardization of data, the database layer of ERP systems is addressed. Since database serve as the foundation for data storage and retrieval, they limit the flexibility of enterprise systems and the chance to adapt to new requirements accordingly. So far, relational databases are widely used. Using a systematic literature approach, recent requirements for ERP systems were identified. Prominent database approaches were assessed against the 23 requirements identified. The results reveal the strengths and weaknesses of recent database approaches. To this end, the results highlight the demand to combine multiple database approaches to fulfill recent business requirements. From a conceptual point of view, this paper supports the idea of federated databases which are interoperable to fulfill future requirements and support business operation. This research forms the basis for renewal of the current generation of ERP systems and proposes to ERP vendors to use different database concepts in the future.