Creatine and creatinine quantified using nuclear magnetic resonance:A method validation study and clinical associations between circulating creatine and fatigue in kidney transplant recipients

Background: A potential contributor to fatigue in kidney transplant recipients (KTR) may be impaired creatine homeostasis. We developed and validated a high-throughput NMR assay allowing for simultaneous measurement of circulating creatine and creatinine, and determined plasma creatine and estimated intramuscular creatine concentrations in KTRs, delineated their determinants and explored their associations with self-reported fatigue.Methods: An NMR assay was developed and validated for measurement of circulating creatinine and creatine concentrations. Plasma creatine and creatinine concentrations were measured in 618 KTR. Fatigue was assessed using the checklist individual strength. Associations of creatine parameters with fatigue was assessed using linear mixed effect models.Results: The NMR-based assay had good sensitivity, precision and demonstrated linearity across a large range of values. Among KTR, the mean age was 56 ± 13 years, 62% were men and eGFR was 54 ± 18 ml/min/1.73 m2. Plasma creatine concentration was 27 [19–39] µmol/L. Estimated intramuscular creatine concentration was 27 ± 7 mmol/kg. Higher plasma creatine concentration and higher estimated intramuscular creatine concentration were independently associated with a lower total fatigue score and less motivation problems.Conclusion: An NMR method for measurement of circulating creatine and creatinine which offers the potential for accurate and efficient quantification was developed. The found associations suggest that improving creatine status may play a beneficial role in mitigating fatigue.</p

Antiarrhythmic and antioxidant activity of novel pyrrolidin-2-one derivatives with adrenolytic properties

A series of novel pyrrolidin-2-one derivatives (17 compounds) with adrenolytic properties was evaluated for antiarrhythmic, electrocardiographic and antioxidant activity. Some of them displayed antiarrhythmic activity in barium chloride-induced arrhythmia and in the rat coronary artery ligation-reperfusion model, and slightly decreased the heart rate, prolonged P–Q, Q–T intervals and QRS complex. Among them, compound EP-40 (1-[2-hydroxy-3-[4-[(2-hydroxyphenyl)piperazin-1-yl]propyl]pyrrolidin-2-one showed excellent antiarrhythmic activity. This compound had significantly antioxidant effect, too. The present results suggest that the antiarrhythmic effect of compound EP-40 is related to their adrenolytic and antioxidant properties. A biological activity prediction using the PASS software shows that compound EP-35 and EP-40 can be characterized by antiischemic activity; whereas, compound EP-68, EP-70, EP-71 could be good tachycardia agents

QSAR studies on a number of pyrrolidin-2-one antiarrhythmic arylpiperazinyls

The activity of a number of 1-[3-(4-arylpiperazin-1-yl)propyl]pyrrolidin-2-one antiarrhythmic (AA) agents was described using the quantitative structure–activity relationship model by applying it to 33 compounds. The molecular descriptors of the AA activity were obtained by quantum chemical calculations combined with molecular modeling calculations. The resulting model explains up to 91% of the variance and it was successfully validated by four tests (LOO, LMO, external test, and Y-scrambling test). Statistical analysis shows that the AA activity of the studied compounds depends mainly on the PCR and JGI4 descriptors

On the emergence of molecular structure

The structure of {a(+/-),a(+/-),b(+/-)}-type Coulombic systems is characterized by the effective ground-state density of the a-type particles, computed via nonrelativistic quantum mechanics without introduction of the Born-Oppenheimer approximation. A structural transition is observed when varying the relative mass of the a- and b-type particles, e.g., between atomic H- and molecular H-2(+). The particle-density profile indicates a molecular-type behavior for the positronium ion, Ps(-)

Vibrational energy levels with arbitrary potentials using the Eckart-Watson Hamiltonians and the discrete variable representation

084102, doi:10.1063/1.2756518info:eu-repo/semantics/publishe

Study of the Cytotoxic and Antifungal Activities of Neolignans 8.O.4´ and Structurally Related Compounds

In the present work we report the antifungal and cytotoxic activities of a neolignan 8.O.4´series. The most active antifungal compounds show a significant cytotoxic effect which might be related