ABSTRACT
This study evaluated the significance of serum pancreatitis-associated protein (PAP) assay, as a marker of hepatocellular carcinoma (HCC), in comparison and combined with alpha-fetoprotein (AFP) assay. Sixty-five patients with HCC, 59 with liver cirrhosis (LC) and 68 asymptomatic controls (C) were studied. PAP and AFP values significantly increased from C to LC and HCC group (p < 0.0001). The area under receiver-operating characteristic (ROC) curve for the two markers was not statistically different. At 100% specificity, ROC analysis gave a cut-off level for AFP of 166 IU/l with 40% sensitivity, and a cut-off level of 240 microg/l for PAP with 23% sensitivity. Diagnostic accuracy of combined AFP and PAP assay was significantly higher than AFP alone. Sensitivity according to tumor size also improved using the combined assay, especially for tumors <5 cm. Stepwise logistic regression indicated that AFP, but not PAP, was associated with an increased risk of developing HCC. These data confirm that PAP production is increased only in some cases of HCC and that the combined PAP and AFP assays do not significantly improve specificity over AFP assay alone. Consequently, PAP assay can only be recommended in cases of justified suspicion of HCC with negative AFP.
Subject(s)
Acute-Phase Proteins/analysis , Antigens, Neoplasm , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/blood , Lectins, C-Type , Liver Neoplasms/blood , alpha-Fetoproteins/analysis , Adult , Aged , Female , Humans , Logistic Models , Male , Middle Aged , Pancreatitis-Associated Proteins , Sensitivity and SpecificityABSTRACT
Since PAP is a stress protein expressed in human pancreas during pancreatitis but also constitutively synthesized in the small intestine, we looked whether its expression would be altered in patients with celiac disease. Serum PAP concentrations were determined consecutively in 54 patients with celiac disease on a free diet (group A), in 47 patients with celiac disease on a gluten-free diet (group B), in 22 patients with other intestinal pathologies but with normal intestinal mucosa (group C), in 14 patients with retarded growth, no gastrointestinal disease and normal intestinal mucosa (group D), and in 17 controls (group E). Serum PAP levels (ng/ml) were significantly higher in group A (127.3 +/- 56.8) than in the other groups (B: 47.2 +/- 20.5; C: 51.5 +/- 32.2; D: 47 +/- 22.8; E: 27.6 +/- 9.0), which were not different from each other. In group A, a positive correlation was observed between serum PAP values and antigluten antibody levels (vs. AGA IgG r = 0.58, p < 0.001; vs. AGA IgA r = 0.66, p < 0.001). Furthermore, 12 patients from group A were evaluated after 10-12 months of gluten-free diet and in all of them PAP serum concentration had decreased (mean +/- SE before the diet 122.5 +/- 36.4, after the diet 48.7 +/- 13.7, p < 0.0001). In addition, we performed an immunocytochemical study to localize PAP in the intestinal mucosa of patients from all groups except E. PAP was localized to the Paneth cells and to some globet cells, in patients with mucosal atrophy as well as in those with normal mucosa with no obvious quantitative difference. We concluded that in patients with celiac disease the active phase of the disease was accompanied by an increased serum concentration of PAP. Further studies are necessary to understand the mechanism leading to PAP elevation in the serum of patients with celiac disease.
Subject(s)
Acute-Phase Proteins/metabolism , Antigens, Neoplasm , Biomarkers, Tumor , Celiac Disease/blood , Lectins, C-Type , Lectins/blood , Adult , Animals , Biopsy , Child , Child, Preschool , Female , Glutens/immunology , Glutens/metabolism , Humans , Immunoglobulin A/metabolism , Immunoglobulin G/metabolism , Immunohistochemistry , Infant , Intestinal Mucosa/pathology , Intestine, Small/pathology , Jejunum/pathology , Pancreatitis-Associated Proteins , RabbitsABSTRACT
A few derivatives of natural, bicyclic monoterpenes, which are propranolol analogs, were synthetized. Those compounds were studied pharmacologically in order to determine their toxicity, antiarrhythmic activity in selected experimental models of arrhythmia, the local anesthetic effect and influence on the cardiovascular system. The tested compounds showed a less potent or similar toxicity towards reference drugs, were devoid of an antiarrhythmic activity in the model of barium arrhythmia, yet some of them (compounds 9 and 12) increased the arrhythmogenic dose of strophanthin. All the compounds studied had a local anesthetic effect stronger than lidocaine in infiltration anesthesia, and compound 8--also in surface anesthesia.
