A reference frame for blood volume in children and adolescents

BACKGROUND: Our primary purpose was to determine the normal range and variability of blood volume (BV) in healthy children, in order to provide reference values during childhood and adolescence. Our secondary aim was to correlate these vascular volumes to body size parameters and pubertal stages, in order to determine the best normalisation parameter. METHODS: Plasma volume (PV) and red cell volume (RCV) were measured and F-cell ratio was calculated in 77 children with idiopathic nephrotic syndrome in drug-free remission (mean age, 9.8 ± 4.6 y). BV was calculated as the sum of PV and RCV. Due to the dependence of these values on age, size and sex, all data were normalised for body size parameters. RESULTS: BV normalised for lean body mass (LBM) did not differ significantly by sex (p < 0.376) or pubertal stage (p < 0.180), in contrast to normalisation for the other anthropometric parameters. There was no significant difference between reference values for children and adults. CONCLUSION: LBM was the anthropometric index most closely correlated to vascular fluid volumes, independent of age, gender and pubertal stage

Practical consensus guidelines for the management of enuresis

Despite the high prevalence of enuresis, the professional training of doctors in the evaluation and management of this condition is often minimal and/or inconsistent. Therefore, patient care is neither optimal nor efficient, which can have a profound impact on affected children and their families. Once comprehensive history taking and evaluation has eliminated daytime symptoms or comorbidities, monosymptomatic enuresis can be managed efficaciously in the majority of patients. Non-monosymptomatic enuresis is often a more complex condition; these patients may benefit from referral to specialty care centers. We outline two alternative strategies to determine the most appropriate course of care. The first is a basic assessment covering only the essential components of diagnostic investigation which can be carried out in one office visit. The second strategy includes several additional evaluations including completion of a voiding diary, which requires extra time during the initial consultation and two office visits before treatment or specialty referral is provided. This should yield greater success than first-line treatment. Conclusion: This guideline, endorsed by major international pediatric urology and nephrology societies, aims to equip a general pediatric practice in both primary and secondary care with simple yet comprehensive guidelines and practical tools (i.e., checklists, diary templates, and quick-reference flowcharts) for complete evaluation and successful treatment of enuresis

Resistance to caspase-8 and -9 fragments in a malignant pleural mesothelioma cell line with acquired cisplatin-resistance

Apoptotic cysteine–aspartate proteases (caspases) are essential for the progression and execution of apoptosis, and detection of caspase fragmentation or activity is often used as markers of apoptosis. Cisplatin (cis-diamminedichloroplatinum (II)) is a chemotherapeutic drug that is clinically used for the treatment of solid tumours. We compared a cisplatin-resistant pleural malignant mesothelioma cell line (P31res1.2) with its parental cell line (P31) regarding the consequences of in vitro acquired cisplatin-resistance on basal and cisplatin-induced (equitoxic and equiapoptotic cisplatin concentrations) caspase-3, -8 and -9 fragmentation and proteolytic activity. Acquisition of cisplatin-resistance resulted in basal fragmentation of caspase-8 and -9 without a concomitant increase in proteolytic activity, and there was an increased basal caspase-3/7 activity. Similarly, cisplatin-resistant non-small-cell lung cancer cells, H1299res, had increased caspase-3 and -9 content compared with the parental H1299 cells. In P31 cells, cisplatin exposure resulted in caspase-9-mediated caspase-3/7 activation, but in P31res1.2 cells the cisplatin-induced caspase-3/7 activation occurred before caspase-8 or -9 activation. We therefore concluded that in vitro acquisition of cisplatin-resistance rendered P31res1.2 cells resistant to caspase-8 and caspase-9 fragments and that cisplatin-induced, initiator-caspase independent caspase-3/7 activation was necessary to overcome this resistance. Finally, the results demonstrated that detection of cleaved caspase fragments alone might be insufficient as a marker of caspase activity and ensuing apoptosis induction

Novel Mitochondrial Substrates of Omi Indicate a New Regulatory Role in Neurodegenerative Disorders

The mitochondrial protease OMI (also known as HtrA2) has been implicated in Parkinson's Disease (PD) and deletion or protease domain point mutations have shown profound neuropathologies in mice. A beneficial role by OMI, in preserving cell viability, is assumed to occur via the avoidance of dysfunctional protein turnover. However relatively few substrates for mitochondrial Omi are known. Here we report our identification of three novel mitochondrial substrates that impact metabolism and ATP production. Using a dual proteomic approach we have identified three interactors based upon ability to bind to OMI, and/or to persist in the proteome after OMI activity has been selectively inhibited. One candidate, the chaperone HSPA8, was common to each independent study. Two others (PDHB subunit and IDH3A subunit) did not appear to bind to OMI, however persisted in the mito-proteome when OMI was inhibited. Pyruvate dehydrogenase (PDH) and isocitrate dehydrogenase (IDH) are two key Kreb's cycle enzymes that catalyse oxidative decarboxylation control points in mitochondrial respiration. We verified both PDHB and IDH3A co-immunoprecipitate with HSPA8 and after elution, were degraded by recombinant HtrA2 in vitro. Additionally our gene expression studies, using rotenone (an inhibitor of Complex I) showed Omi expression was silenced when pdhb and idh3a were increased when a sub-lethal dose was applied. However higher dose treatment caused increased Omi expression and decreased levels of pdhb and idh3a transcripts. This implicates mitochondrial OMI in a novel mechanism relating to metabolism

Lack of evidence of hypervolemia in children with insulin-dependent diabetes mellitus

Hypervolemia is considered to play a major role in the pathogenesis of diabetic vasculo- and nephropathy. The aim of our study is to determine whether children and adolescents with insulin-dependent diabetes mellitus (IDDM) experience alterations in blood volume (BV) before onset of apparent nephropathy. BV (calculated as the sum of measured plasma volume (PV) and red cell volume (RCV)) was determined in 31 children (9-16 yr) with a mean duration of IDDM of 6.6 yr and without microalbuminuria. Due to dependence of these values on age, size and sex, all data were normalised for body size parameters. While no statistical difference for BV normalised for lean body mass (LBM) (86.98 +/- 9.5 ml/kg) was found in diabetic children compared with our control population (84.91 +/- 12.08 ml/kg), a difference could be shown when normalised for body surface area (BSA) (diabetic children 2.37 +/- 0.3 L/m(2); control population 2.15 +/- 0.38 L/m(2), p=0.002). Increased BV is only present when normalising for BSA and not for the theoretical superior LBM-index. Because the study population exhibited a poor glycemic control (HbAlc 10.2 +/- 2.4%), an influence of glucosuria-induced polyuria on BV cannot be excluded. Taking into account these limitations our data do not confirm the presence of hypervolemia before onset of diabetic nephropathy