Leptin treatment ameliorates acute lung injury in rats with cerulein-induced acute pancreatitis.

AIM: To determine the effect of exogenous leptin on acute lung injury (ALI) in cerulein-induced acute pancreatitis (AP). METHODS: Forty-eight rats were randomly divided into 3 groups. AP was induced by intraperitoneal (i.p.) injection of cerulein (50 microg/kg) four times, at 1 h intervals. The rats received a single i.p. injection of 10 mug/kg leptin (leptin group) or 2 mL saline (AP group) after cerulein injections. In the sham group, animals were given a single i.p. injection of 2 mL saline. Experimental samples were collected for biochemical and histological evaluations at 24 h and 48 h after the induction of AP or saline administration. Blood samples were obtained for the determination of amylase, lipase, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, macrophage inflammatory peptide (MIP)-2 and soluble intercellular adhesion molecule (sICAM)-1 levels, while pancreatic and lung tissues were removed for myeloperoxidase (MPO) activity, nitric oxide (NOx) level, CD40 expression and histological evaluation. RESULTS: Cerulein injection caused severe AP, confirmed by an increase in serum amylase and lipase levels, histopathological findings of severe AP, and pancreatic MPO activity, compared to the values obtained in the sham group. In the leptin group, serum levels of MIP-2, sICMA-1, TNF-alpha, and IL-1beta, pancreatic MPO activity, CD40 expression in pancreas and lung tissues, and NOx level in the lung tissue were lower compared to those in the AP group. Histologically, pancreatic and lung damage was less severe following leptin administration. CONCLUSION: Exogenous leptin attenuates inflamma-tory changes, and reduces pro-inflammatory cytokines, nitric oxide levels, and CD40 expression in cerulein-induced AP and may be protective in AP associated ALI.

Comparison of 1998 WHO/ISUP and 1973 WHO classifications for interobserver variability in grading of papillary urothelial neoplasms of the bladder. Pathological evaluation of 258 cases.

AIM: Our aim was to compare the interobserver variability between the 1998 WHO/ISUP and 1973 WHO classifications. METHODS: 258 consecutive papillary urothelial carcinomas were reviewed by two pathologists and assigned a tumor grade according to the 1973 WHO and 1998 WHO/ISUP without the knowledge of primary diagnosis and clinical follow-up. All cases were also histologically staged by the two pathologists separately as follows: pTa (noninvasive), pT1 (lamina propria invasion only), pT2 (muscularis propria invasion). Findings of both pathologists and degree of agreement were compared statistically by using Pearson's chi(2) test and kappa statistics respectively. A kappa value of 0.21-0.40 is accepted as fair, 0.41-0.60 moderate and 0.61-0.80 substantial agreement. RESULTS: Regardless of the pathologist, tumor grades of two classifications correlated to each other and the pathological stage (p < 0.05). Overall degree of agreement between pathologists was higher in the 1998 WHO/ISUP (kappa 0.59) than the 1973 WHO (kappa 0.41), but both were still moderate. Papillary urothelial neoplasia with low malignant potential was the group of 1998 WHO/ISUP that showed the lowest degree of agreement and if excluded, interobserver variability of the 1998 WHO/ISUP decreased significantly (kappa 0.84). CONCLUSION: The diagnosis of papillary urothelial neoplasia with low malignant potential and the criteria that differentiates it from low-grade carcinomas needs improvement in order to compare the different studies and therapies and to provide more accurate information for management.

Role of ghrelin and leptin in predicting the severity of acute pancreatitis.

Ghrelin and leptin are the hormones that influence endocrine and exocrine functions of the pancreas and regulate feeding behaviors and energy metabolism. The aim of this study was to investigate the levels of ghrelin and leptin in pancreatitis of different severities and the relation of these hormones with blood glucose level and proinflammatory cytokines. The study was performed on 90 Wistar Albino rats. Three experimental groups composed of 30 rats were established: control group, 0.9% NaCl solution was injected intraperitoneally (i.p); acute edematous pancreatitis (AEP) group, 1 microg/100 g cerulein was injected i.p. five times, at 1-hr intervals; and acute necrotizing pancreatitis (ANP) group, 500 mg/100 g L-arginine was injected i.p. Ten animals in each group were sacrificed under anesthesia 12, 24 and 48 hr after the last injection. After blood withdrawal, the pancreas was totally excised. The levels of blood sugar, lipase, serum tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), ghrelin, and leptin were investigated and histopathologic examination was performed. Following pancreatitis induction, serum ghrelin levels increased at 24 hr and reached the peak level at 48 hr. Its level in the AEP group was higher than in the ANP group. Serum leptin levels in the AEP and ANP groups increased after 12 hr and stayed at high levels until 48 hr compared with the control group. Similarly to ghrelin and leptin, blood glucose levels increased in both pancreatitis groups, but the increase was more prominent in the ANP group, with levels >200 mg/ml at 48 hr. The levels of TNF-alpha and IL-1beta in the AEP and ANP groups reached the peak level at 24 hr and then decreased to a level close to that of the control group at 48 hr. We conclude that serum leptin and ghrelin levels increase in the first 48 hr of AEP and ANP. As the serum ghrelin levels in ANP are higher than in AEP, it can be used as a marker to show the severity of pancreatitis. While TNF-alpha and IL-1beta can be used as a prognostic factor in the first 24 hr, ghrelin and leptin can be used subsequently.