Serum neutrophil gelatinase-associated lipocalin (NGAL) correlates with clinical and endoscopic activity in ulcerative colitis but fails to predict activity in Crohn's disease.

Serum neutrophil gelatinase-associated lipocalin (NGAL) is a low molecular weight protein released from activated neutrophils and intestine epithelium whose mRNA expression is increased in inflamed intestinal tissue. The purpose of this study was to explore the relationship between serum NGAL level and activity of inflammatory bowel diseases. A total of 120 patients, 79 with Crohn's disease (CD) and 41 with ulcerative colitis (UC) were prospectively included into the study. Serum NGAL was measured by ELISA. The inflammatory activity of UC was assessed by Mayo score and of CD by CDAI and SES-CD scoring systems. Increasing endoscopic severity of UC from remission/mild to moderate/severe was associated with increasing NGAL levels from 46.9 to 66.4 ng/ml (P = 0.002). NGAL concentrations were significantly lower in patients with complete endoscopic and histologic remission than in the active UC (46.9 versus 66.4 ng/ml, P = 0.009). Also deterioration of the clinical activity of UC patients was associated with increasing level of NGAL from 44.9 in remission/mild to 68.0 ng/ml in moderate/severe grade (P = 0.002). NGAL levels correlated with CRP (r = 0.49), ESR (r = 0.48) and iron concentrations (r = -0.63), but not with faecal calprotectin. NGAL showed ability to distinguish endoscopically active from inactive UC with AUC-ROC of 0.758 (sensitivity 96% and specificity 54%). However NGAL levels showed no significant relationship with either clinical or endoscopic activity of CD. We conclude that serum NGAL level corresponds to clinical and endoscopic activity of UC and accurately predicts disease endoscopic remission.

Distinctive biochemical pattern associated with resistance of hepatocytes in hepatocyte nodules during liver carcinogenesis.

Hepatocyte ("hyperplastic") nodules induced in the liver by initiation with diethylnitrosamine and selected by dietary 2-acetylaminofluorene plus partial hepatectomy ("resistant hepatocyte model") have a special pattern of biochemical behavior and metabolic activity different than that seen acutely with many xenobiotics including many promoting agents and carcinogens. The nodule cells show a very low uptake of 2-acetylaminofluorene, relative to surrounding and normal liver, low levels of activity in the cytochromes P-450 and aryl hydrocarbon hydroxylase, high levels of activity in gamma-glutamyltransferase, microsomal epoxide hydrolase, soluble glutathione-S-transferase and soluble UDP-glucuronyltransferase (UDP-GT(1)) and elevated levels of glutathione. This metabolic pattern appears to maximize the resistance of the nodules to xenobiotics generally, such as 2-acetylaminofluorene, and thereby may account for the resistant behavior of nodule hepatocytes to the inhibition of cell proliferation and the cytotoxicity by 2-acetylaminofluorene and other carcinogens. The possible importance of this seemingly new metabolic program in carcinogenesis is discussed briefly.

Carcinogenesis in vitro. II. Chemical transformation of diploid human cell cultures: A rare event.

Seventy-five diploid human cell s-rains were subjected to a number of chemical carcinogens, including urethane and polycyclic hydrocarbons. In most cases, no visible morphological alterations were induced by any treatment. Development of morphologically altered foci was noticed in urethane-treated cultures derived from a patient with von Recklinghausen's disease. This disease is transmitted by an autosomal dominant gene, and has a high rate of spontaneous transformation of neurofibromas to neurofibrosarcomas. Attempts to isolate continuous cell lines from altered foci were successful in only two of several attempts. These continuous cell lines demonstrate altered morphology, loss of contact inhibition, accelerated growth rate, and have attained over 240 generations in a period of 140 weeks. Untreated control cultures became terminal by the 20th generation. Giemsa banding procedures showed that the chromosomal complement consisted of heteroploid human chromosomes. A second diploid cell strain derived from the above patient's sibling, also suffering from von Recklinghausen's disease, likewise was morphologically altered by urethane. Chemical transformation of human cells is difficult to induce; however, selection of genetically predisposed cells and prolonged, intermittent, and repeated chemical treatment may be important factors in achieving transformation.