Inflammation and innate immunity in renal ischemia/reperfusion injury

The studies in this thesis describe the systematical search for factors involved in the pathophysiology of human renal I/R injury. Many of the processes assumed to be involved in renal I/R injury based on animal studies could not be confirmed in our clinical study in humans. However, we found new evidence of complement activation and endothelial cell activation in human renal I/R injury. Moreover, there were large differences between deceased and living donor kidneys; brain dead donor kidneys have a unique proinflammatory cytokine release after reperfusion. Finally it appears that both brain dead and cardiac dead donor kidneys are not able to upregulate their metabolism-related genes upon reperfusion as living donor kidneys do, indicating that failure to restart metabolism may be a factor expanding I/R injury. All of these findings contribute to the understanding of renal I/R injury in humans and instigate the further search for therapeutical modalities to limit renal I/R injury.Financial support by Clinical Science Systems, KCI, Covidien, Ethicon, Astellas and Nederlandse Transplantatie Vereniging for printing this thesis is gratefully acknowledged.UBL - phd migration 201

Pre-main-sequence population in NGC 1893 region

In this paper we continued our efforts to understand the star formation scenario in and around the young cluster NGC 1893. We used a sample of the young stellar sources (YSOs) identified on the basis of multiwavelength data (optical, near-infrared (NIR), mid-infrared (MIR) and X-ray) to study the nature of YSOs associated with the region. The identified YSOs show an age spread of ~ 5 Myr. The YSOs located near the nebulae at the periphery of the cluster are relatively younger in comparison to those located within the cluster region. The present results are in accordance with those obtained by us in previous studies. Other main results from the present study are: 1) the fraction of disk bearing stars increases towards the periphery of the cluster; 2) there is an evidence supporting the notion that the mechanisms for disk dispersal operate less efficiently for low-mass stars; 3) the sample of Class II sources is found to be relatively older in comparison to that of Class III sources. A comparison of various properties of YSOs in the NGC 1893 region with those in the Tr 37/ IC 1396 region is also discussed.Comment: Accepted for publication in New Astronom

Metabolic needs of the kidney graft undergoing normothermic machine perfusion

Normothermic machine perfusion (NMP) is emerging as a novel preservation strategy. During NMP, the organ is maintained in a metabolically active state that may not only provide superior organ preservation, but that also facilitates viability testing before transplantation, and ex situ resuscitation of marginal kidney grafts. Although the prevailing perfusion protocols for renal NMP are refined from initial pioneering studies concerning short periods of NMP, it could be argued that these protocols are not optimally tailored to address the putatively compromised metabolic plasticity of marginal donor grafts (i.e., in the context of viability testing and/or preservation), or to meet the metabolic prerequisites associated with prolonged perfusions and the required anabolic state in the context of organ regeneration. Herein, we provide a theoretical framework for the metabolic requirements for renal NMP. Aspects are discussed along the lines of carbohydrates, fatty acids, amino acids, and micronutrients required for optimal NMP of an isolated kidney. In addition, considerations for monitoring aspects of metabolic status during NMP are discussed.Transplant surger

Quantification of myocardial creatine and triglyceride content in the human heart: precision and accuracy of in vivo proton magnetic resonance spectroscopy

Background Proton magnetic resonance spectroscopy (H-1-MRS) of the human heart is deemed to be a quantitative method to investigate myocardial metabolite content, but thorough validations of in vivo measurements against invasive techniques are lacking.Purpose To determine measurement precision and accuracy for quantifications of myocardial total creatine and triglyceride content with localized H-1-MRS.Study type Test-retest repeatability and measurement validation study.Subjects Sixteen volunteers and 22 patients scheduled for open-heart aortic valve replacement or septal myectomy.Field Strength/Sequence Prospectively ECG-triggered respiratory-gated free-breathing single-voxel point-resolved spectroscopy (PRESS) sequence at 3 T.Assessment Myocardial total creatine and triglyceride content were quantified relative to the total water content by fitting the H-1-MR spectra. Precision was assessed with measurement repeatability. Accuracy was assessed by validating in vivo H-1-MRS measurements against biochemical assays in myocardial tissue from the same subjects.Statistical Tests Intrasession and intersession repeatability was assessed using Bland-Altman analyses. Agreement between H-1-MRS measurements and biochemical assay was tested with regression analyses.Results The intersession repeatability coefficient for myocardial total creatine content was 41.8% with a mean value of 0.083% +/- 0.020% of the total water signal, and 36.7% for myocardial triglyceride content with a mean value of 0.35% +/- 0.13% of the total water signal. Ex vivo myocardial total creatine concentrations in tissue samples correlated with the in vivo myocardial total creatine content measured with H-1-MRS: n = 22, r = 0.44; P < 0.05. Likewise, ex vivo myocardial triglyceride concentrations correlated with the in vivo myocardial triglyceride content: n = 20, r = 0.50; P < 0.05.Data Conclusion We validated the use of localized H-1-MRS of the human heart at 3 T for quantitative assessments of in vivo myocardial tissue metabolite content by estimating the measurement precision and accuracy.Level of Evidence 2Technical Efficacy Stage 2Cardiovascular Aspects of Radiolog

Probing exotic phenomena at the interface of nuclear and particle physics with the electric dipole moments of diamagnetic atoms: A unique window to hadronic and semi-leptonic CP violation

The current status of electric dipole moments of diamagnetic atoms which involves the synergy between atomic experiments and three different theoretical areas -- particle, nuclear and atomic is reviewed. Various models of particle physics that predict CP violation, which is necessary for the existence of such electric dipole moments, are presented. These include the standard model of particle physics and various extensions of it. Effective hadron level combined charge conjugation (C) and parity (P) symmetry violating interactions are derived taking into consideration different ways in which a nucleon interacts with other nucleons as well as with electrons. Nuclear structure calculations of the CP-odd nuclear Schiff moment are discussed using the shell model and other theoretical approaches. Results of the calculations of atomic electric dipole moments due to the interaction of the nuclear Schiff moment with the electrons and the P and time-reversal (T) symmetry violating tensor-pseudotensor electron-nucleus are elucidated using different relativistic many-body theories. The principles of the measurement of the electric dipole moments of diamagnetic atoms are outlined. Upper limits for the nuclear Schiff moment and tensor-pseudotensor coupling constant are obtained combining the results of atomic experiments and relativistic many-body theories. The coefficients for the different sources of CP violation have been estimated at the elementary particle level for all the diamagnetic atoms of current experimental interest and their implications for physics beyond the standard model is discussed. Possible improvements of the current results of the measurements as well as quantum chromodynamics, nuclear and atomic calculations are suggested.Comment: 46 pages, 19 tables and 16 figures. A review article accepted for EPJ