New paths for the NGAL shuttle. The molecular path taken by NGAL may be largely dependent on the type of molecule being shuttled. Apo-NGAL denotes NGAL that is devoid of siderophore or iron. ECM denotes extra-cellular matrix, and VEGF denotes vascular endothelial growth factor.
Prasad Devarajan. Cancer Ther. 2007; 5(B): 463–470.
Elevated Serum Neutrophil Gelatinase-Associated Lipocalin Is an Early Predictor of Severity and Outcome in Acute Pancreatitis.
OBJECTIVES:About 210,000 new cases of acute pancreatitis (AP) involving
reversible inflammation of the pancreas are reported in the United States every
year. About one-fourth of all patients with AP go on to develop severe acute
pancreatitis (SAP), which, unlike uncomplicated or mild acute pancreatitis (MAP,
usually a self-limiting disease), constitutes a life-threatening condition with
systemic complications, chiefly multiorgan dysfunction. An early prediction of
the severity and outcome of patients with acute pancreatitis (AP) can lead to
better treatment regimens for patients with SAP. There is currently no
established biomarker for the early diagnosis of SAP. In this study, we
investigated the potential of serum neutrophil gelatinase-associated lipocalin
(NGAL) as an early marker to distinguish severe (SAP) from MAP and examine its
ability to predict the prognosis of patients with SAP.METHODS:To check the time
kinetics of rise in NGAL during AP, we quantified NGAL levels in sera from mice
with MAP or SAP at various time points (6, 12, 24 and 48 h) using sandwich
enzyme-linked immunosorbent assay. NGAL levels were also quantified in serum from
28 MAP and 16 SAP cases and compared with 28 chronic pancreatitis and 30 healthy
control samples. Samples collected within 5 days from onset of symptoms were
included. The relationship of NGAL levels with survival and multiorgan failure
(MOF) in SAP was also examined.RESULTS:Although NGAL levels were significantly
higher in mice with both MAP and SAP 6 h after induction (compared to control
animals), only mice with SAP exhibited a significant increase in NGAL levels at
24 h (P=0.003). NGAL levels declined at 48 h after induction in animals with both
MAP and SAP but did not reach baseline levels. Among patients, mean (+/-s.e.)
serum NGAL level was significantly higher in SAP (634+/-139 ng/ml) compared to
MAP (84.7+/-7 ng/ml, P=0.0001). On subanalysis, the difference between MAP and
SAP cases was significant in the first 48 h but not at 72, 96, or 120 h. NGAL was
100%, 96%, 97%, and 84% specific and 100%, 87.5%, 92%, and 94% sensitive in
distinguishing SAP from MAP at 48, 72, 96, and 120 h, respectively, after the
onset of symptoms. NGAL levels were significantly higher in SAP cases complicated
by MOF (P=0.004), and high NGAL levels in SAP appeared to correlate with a fatal
outcome.CONCLUSIONS:Our data provide the first evidence for the potential of
serum NGAL as an early marker to distinguish MAP from SAP. Further, high NGAL
levels predict MOF and fatal outcome in patients with SAP. This study provides
sufficient evidence for multi-institutional randomized trials for estimating the
potential of NGAL as early biomarker for SAP.
Chakraborty S, et al. Elevated Serum Neutrophil Gelatinase-Associated Lipocalin Is an Early Predictor of Severity and Outcome in Acute Pancreatitis. Am J Gastroenterol. 2010 Feb 23. [Epub ahead of print]
Chakraborty S, et al. Elevated Serum Neutrophil Gelatinase-Associated Lipocalin Is an Early Predictor of Severity and Outcome in Acute Pancreatitis. Am J Gastroenterol. 2010 Feb 23. [Epub ahead of print]
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