Urine recirculation prolongs normothermic kidney perfusion via more optimal metabolic homeostasis—a proteomics study

We describe a proteomics analysis to determine the molecular differences between normothermically perfused (normothermic machine perfusion, NMP) human kidneys with urine recirculation (URC) and urine replacement (UR). Proteins were extracted from 16 kidney biopsies with URC (n = 8 donors after brain death [DBD], n = 8 donors after circulatory death [DCD]) and three with UR (n = 2 DBD, n = 1 DCD), followed by quantitative analysis by mass spectrometry. Damage-associated molecular patterns (DAMPs) were decreased in kidney tissue after 6 hours NMP with URC, suggesting reduced inflammation. Vasoconstriction was also attenuated in kidneys with URC as angiotensinogen levels were reduced. Strikingly, kidneys became metabolically active during NMP, which could be enhanced and prolonged by URC. For instance, mitochondrial succinate dehydrogenase enzyme levels as well as carbonic anhydrase were enhanced with URC, contributing to pH stabilization. Levels of cytosolic and the mitochondrial phosphoenolpyruvate carboxykinase were elevated after 24 hours of NMP, more prevalent in DCD than DBD tissue. Key enzymes involved in glucose metabolism were also increased after 12 and 24 hours of NMP with URC, including mitochondrial malate dehydrogenase and glutamic-oxaloacetic transaminase, predominantly in DCD tissue. We conclude that NMP with URC permits prolonged preservation and revitalizes metabolism to possibly better cope with ischemia reperfusion injury in discarded kidneys.     

MEROPENEM IN THE TREATMENT OF FEBRILE NEUTROPENIC CHILDREN

The aim of this retrospective study was to evaluate the clinical effectiveness of meropenem in immunocompromised children. Between January 1998 and December 2002 in the hemato-oncological units of our hospital meropenem was used in 87 febrile events diagnosed in 55 patients, and 328 bacterial cultures were evaluated. Microorganisms were detected and identified in 64 of the 328 hemocultures; there was a predominance of gram-positive strains (67%). In 49.4% the infection was documented microbiologically. In 16 additional cases the infection was proven clinically and 32.2% of the episodes were considered to be fever of unknown origin. The success rate of the meropenem therapy—excluding the proven fungal or coagulase-negative Staphylococcus infections—was 72.9% and for the whole cohort 49.4%. The results demonstrate that meropenem is effective and well-tolerated when used for the treatment of neutropenic cancer children.     

Genetic factors explain a significant part of associations between adolescent well-being and the social environment

European Child & Adolescent Psychiatry - Socio-environmental factors play an important role in adolescent well-being, but potential genetic contributions to these associations are rarely...     

Measurement of deoxyinosine adduct: Can it be a reliable tool to assess oxidative or nitrosative DNA damage?

Adenosine deaminases (ADA) are key enzymes that deaminate adenosine (A) or deoxyadenosine (dA) and produce inosine or deoxyinosine (dI), respectively. While ADA only deaminates free dA, reactive nitrogen species (RNS) or reactive oxygen species (ROS) deaminate adenine base on the DNA and leave dI, which is a pre-mutagenic lesion. Therefore, dI adduct in the genomic DNA has been considered a biomarker of DNA damage caused by RNS or by ROS.     

High-frequency modulation of heart rate variability during exercise in patients with COPD

STUDY OBJECTIVES: To evaluate cardiac autonomic modulation in patients with COPD during peak exercise. METHODS: Fifty-three patients with COPD (mean FEV(1), 35% predicted [SD, 11% predicted]; mean PaO(2), 68 mm Hg [SD, 11 mm Hg]; mean PaCO(2), 40 mm Hg [SD, 7 mm Hg]; mean age, 61 years [SD, 10 years]; 26 women and 27 men) and 14 healthy control subjects aged 60 years (SD, 8 years) [seven women and seven men] were studied at rest and during ramped bicycle ergometry to their volitional peak. Patients were not receiving autonomic medications other than inhaled beta-agonist agents and/or anticholinergic agents. Control subjects were not receiving any medications. Cardiac autonomic modulation was assessed via time-frequency analysis (Wigner-Ville) of ECG-derived heart rate variability as the power in the low-frequency (LF) band (ie, 0.04 to 0.15 Hz) and the high-frequency (HF) band (ie, > 0.15 to 0.4 Hz) averaged from > 3 min at rest and minutes 2 through 5 of their exercise period. RESULTS: Patients with COPD had a significantly increased mean, ln-transformed HF band from rest to peak exercise (9.9 ms(2) [SD, 1.4 ms(2)] vs 10.7 ms(2) [SD, 1.4 ms(2)], respectively; p < 0.01), while the HF band was unchanged for the control group (10.7 ms(2) [SD, 1.5 ms(2)] vs 10.4 ms(2) [1.3 ms(2)], respectively; difference not significant). The mean ln-transformed LF band was significantly increased from rest to peak exercise in patients with COPD (10.9 ms(2) [SD, 1.5 ms(2)] vs 11.5 ms(2) [SD, 1.4 ms(2)], respectively; p < 0.01) and in control subjects (10.9 ms(2) [SD, 1.5 ms(2)] vs 11.5 ms(2) [SD, 1.3 ms(2)], respectively; p < 0.01). The mean LF/HF ratio was significantly decreased from rest to peak exercise in patients with COPD (3.1 [SD, 1.5] vs 2.5 [SD, 1.0], respectively; p < 0.01) and was increased in control subjects (1.9 [SD, 0.8] vs 2.4 [1.0], respectively; p < 0.01). When expressed in normalized units ([absolute power of the components]/[total power - very low frequency power] x 100), the HF band was again significantly greater during peak exercise than at rest in the patients with COPD and was unchanged during peak exercise for the control group. Autonomic changes were not significantly correlated with age, gender, body mass index, spirometry, lung volumes, resting gas exchange, or oxygen saturation during exercise. CONCLUSION: These data suggest that, in contrast to control subjects, the balance of sympathetic to parasympathetic cardiac modulation decreases in patients with COPD during maximal volitional exercise.