Interleukin-6 serum levels predict surgical intervention in infants with necrotizing enterocolitis

Background

Symptoms at suspicion of necrotizing enterocolitis (NEC) are often nonspecific and several biomarkers have been evaluated for their discriminative power to both diagnose and predict the course from NEC suspicion to complicated disease requiring surgical intervention. Thus, we aimed to assess the utility of interleukin-6 (IL-6) to predict surgical intervention in infants suffering from NEC and, furthermore, to discriminate infants with starting NEC or late-onset sepsis (LOS).

Colony-Stimulating Factor-1: A Potential Biomarker for Lupus Nephritis

A noninvasive means to predict the onset and recurrence of lupus nephritis (LN) before overt renal injury is needed to optimize and individualize treatment. Colony-stimulating factor-1 (CSF-1) is expressed by kidney tubules at the onset of LN, increases with disease progression, and spills into the circulation in lupus-prone mice. We tested the hypothesis that amplified expression of CSF-1 detected in the serum or urine correlates with intrarenal CSF-1 expression and histopathology (increased macrophage accumulation, activity indices) and clinical kidney disease activity and predicts the onset and recurrence of nephritis in patients with systemic lupus erythematosus (SLE). We found increased serum or urine CSF-1 levels in patients with cutaneous, serositis, and musculoskeletal disease; however, the increase in CSF-1 levels was far greater in LN. Moreover, an elevation in serum or urine CSF-1 levels correlated with increasing intrarenal CSF-1 expression and histopathology. By longitudinally tracking patients, we found that elevated serum CSF-1 heralded the initial onset of disease, and a rise in serum or urine CSF-1 predicted recurrences of LN before clinical evidence of glomerular dysfunction and conventional serologic measures, even in patients with other manifestations of SLE. These findings indicate that serial monitoring for a rise in serum or urine CSF-1 levels in patients with SLE reflects kidney histopathology and may predict renal disease activity and the onset and recurrence of LN more accurately than conventional laboratory measures.     

Global N-acetylaspartate concentration in benign and non-benign multiple sclerosis patients of long disease duration

Background and objective

To examine whether clinically benign multiple sclerosis patients (BMS) show similar losses of their global N-acetylaspartate (NAA) neuronal marker relative to more clinically disabled patients of similar disease duration.

Methods

The whole-brain NAA concentration (WBNAA) was acquired with whole-head non-localizing proton MR spectroscopy. Fractional brain parenchymal volume (fBPV), T₂ and T₁ lesion loads, were obtained from the MRI in: (i) 24 BMS patients: 23.1 ± 7.2 years disease duration, median Expanded Disability Status Scale (EDSS) score of 2.0 (range: 0–3); (ii) 26 non-benign MS patients (non-BMS), 24.5 ± 7.4 years disease duration, median EDSS of 4.0 (range: 3.5–6.5); (iii) 15 healthy controls.

Results

Controls’ 12.4 ± 2.3 mM WBNAA was significantly higher than the BMS's and non-BMS's 10.5 ± 2.4 and 9.9 ± 2.1 mM (both p < 0.02), but the difference between the patients’ groups was not (p > 0.4). Likewise, the controls’ 81.2 ± 4.5% fBPV exceeded the BMS and non-BMS's 77.0 ± 5.8% and 76.3 ± 8.6% (p < 0.03), which were also not different from one another (p > 0.7). BMS patients’ T₁-hypointense lesion load, 2.1 ± 2.2 cm³, was not significantly different than the non-BMS's 4.1 ± 5.4 cm³ (p > 0.08) and T₂-hyperintense loads: 6.0 ± 5.7 cm³ and 8.7 ± 7.8 cm³, were also not different (p > 0.1).

Conclusions

WBNAA differentiates normal controls from MS patients but does not distinguish BMS from more disabled MS patients of similar disease duration. Nevertheless, all MS patients who remain RR for 15+ years suffered WBNAA loss similar to the average RR MS population at fourfold shorter disease duration suggesting relative global neuronal sparing or leveling-off of the neurodegeneration rate.     

Volume loss in the deep gray matter and thalamic subnuclei: a longitudinal study on disability progression in multiple sclerosis

Journal of Neurology - Volume loss in the deep gray matter (DGM) has been reported in patients with multiple sclerosis (MS) already at early stages of the disease and is thought to progress...     

ATP release in human kidney cortex and its mitogenic effects in visceral glomerular epithelial cells

BACKGROUND: In chronic renal failure the sympathetic nervous system is activated. Sympathetic cotransmitters released within the kidney may contribute to the progression of renal disease through receptor-mediated proliferative mechanisms. METHODS: In human renal cortex electrical stimulation induced adenosine 5'-triphosphate (ATP; luciferin-luciferase-assay) and norepinephrine (HPLC) release was measured. ATP release also was induced by alpha1- and alpha2-adrenergic agonists. [3H]-thymidine uptake was tested in human visceral glomerular epithelial cells (vGEC) and mitogen-activated protein kinase (MAPK42/44) activation in vGEC and kidney cortex. The involved P2-receptors were characterized pharmacologically and by RT-PCR. RESULTS: Sympathetic nerve stimulation and alpha-adrenergic agonists induced release of ATP from human kidney cortex. Seventy-five percent of the ATP released originated from non-neuronal sources, mainly through activation of alpha2-adrenergic receptors. ATP (1 to 100 micromol/L) and related nucleotides (1 to 100 micromol/L) increased [3H]-thymidine uptake. The adenine nucleotides ATP, ATPgammaS, ADP and ADPbetaS were about equally potent. UTP, UDP and alpha,beta-methylene ATP had no effect. ATP, ADPbetaS but not alpha,beta-methylene ATP activated MAPK42/44. ATP induced MAPK42/44 activation, and [3H]-thymidine uptake was abolished in the presence of the MAPK inhibitor PD 98059 (100 micromol/L). mRNA for P2X4,5,6,7 and P2Y1,2,4,6,11 were detected in human vGEC by RT-PCR. CONCLUSIONS: In human renal cortex, adrenergic stimulation releases ATP from neuronal and non-neuronal sources. ATP has mitogenic effects in vGEC and therefore the potential to contribute to progression in chronic renal disease. The pattern of purinoceptor agonist effects on DNA synthesis together with the mRNA expression suggests a major contribution of a P2Y1-like receptor.     

Intraperitoneal protein injection in the axolotl: the amphibian kidney as a novel model to study tubulointerstitial activation

BACKGROUND: A substantial body of experimental evidence suggests that protein loading causes activation of proximal tubular epithelial cells with consecutive interstitial fibrosis. These studies have mostly been performed using mammalian in vivo models of glomerular damage or tissue cultures of mammalian tubulointerstitial cells. The kidney of the axolotl contains not only closed nephrons, but also nephrons with ciliated peritoneal funnels called nephrostomes that have access to the peritoneal fluid. Injection of protein into the peritoneal cavity fails to expose closed nephrons to a protein load, but causes selective uptake and transient storage of proteins in tubular epithelial cells of nephrons with nephrostomes. The purpose of the present study was to determine whether (a) the axolotl kidney can be used as a model to assess protein uptake by tubular cells in vivo in the absence of glomerular damage, and (b) this is accompanied by any evidence of tubular epithelial cell activation and interstitial fibrosis. METHODS: Male and female axolotl (80 to 120 g of weight) were given a daily intraperitoneal injection of 1.5 mL endotoxin-free calf serum or saline as control. Kidneys were harvested after 4 or 10 days using perfusion fixation for light microscopy (fibrous tissue stain) and saline perfusion for immunohistochemistry (fibronectin, TGF-beta and collagen I). RESULTS: The findings document selective storage of protein and lipids, progressive with time, in proximal tubular epithelial cells of nephrons draining the coelomic cavity. In addition, progressive focal accumulation of fibrous tissue was noted around protein-storing tubules. Immunohistochemical staining demonstrated the presence of fibronectin and TGF-beta in the tubular epithelial cells and interstitial cells. CONCLUSION: The axolotl kidney provides a novel in vivo model to study tubulointerstitial activation and induction of interstitial fibrosis by protein loading. The findings are independent of alterations of glomerular function that may have potential confounding effects on peritubular hemodynamics, pO2, cell traffic, etc.