Apolipoprotein A2 isoforms associated with exocrine pancreatic insufficiency in early chronic pancreatitis.

BACKGROUND AND AIM: Apolipoprotein A2 (apoA2) isoforms have been reported to undergo the aberrant processing in pancreatic cancer and pancreatic risk populations compared with that in healthy subjects. This study aimed to clarify whether apoA2 isoforms were as useful as N-benzoyl-p-aminobenzoic acid (BT-PABA) test for exocrine pancreatic dysfunction markers in patients with early chronic pancreatitis (ECP). METHODS: Fifty consecutive patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) (n = 18), with ECP (n = 20), and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 12) based on the Rome IV classification and the Japan Pancreatic Association were enrolled in this study. The enrolled patients were evaluated using endoscopic ultrasonography and endoscopic ultrasonography elastography. Five pancreatic enzymes were estimated. Pancreatic exocrine function was analyzed using the BT-PABA test. Lighter and heavier apoA2 isoforms, AT and ATQ levels were measured by enzyme-linked immunosorbent assay methods. RESULTS: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption and smoking among patients with AP-P, FD-P, and ECP. The BT-PABA test and lighter apoA2 isoform, AT level in the enrolled patients had a significant correlation (P < 0.01). The BT-PABA test in patients with ECP was significantly lower (P = 0.04) than that in AP-P. ApoA2-AT level in patients with ECP was lower than that in AP-P, albeit, insignificantly. Interestingly, apo A2-AT level was significantly (P = 0.041) associated with exocrine pancreatic insufficiency by multiple logistic regression analysis. CONCLUSIONS: ApoA2-AT level is a useful tool to evaluate exocrine pancreatic insufficiency in the early stage of chronic pancreatitis.

Combination of high-density cholesterol level, elastic score, and severity of exocrine pancreatic dysfunction may be useful for a predictive factor for patients with early chronic pancreatitis.

BACKGROUND: This study aimed to clarify whether any risk factors including clinical characteristics, endosonographic features, and exocrine pancreatic dysfunction may be useful for a predictive factor for patients with early chronic pancreatitis. METHODS: A total of 163 consecutive patients that presented with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) (n = 46), early chronic pancreatitis (ECP) (n = 47), and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 70) based on the Rome III classification and the Japan Pancreatic Association were included in this study. The enrolled patients were evaluated using endosonography (EUS) and EUS elastography. The levels of the five pancreatic enzymes were measured. Pancreatic exocrine function was analyzed using N-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA). RESULTS: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption, and smoking among patients with AP-P, FD-P, and ECP. The ratio of BT-PABA test less than 35% in patients with ECP was significantly (P = 0.043) higher than in AP-P patients. Elastic score was a useful tool to differentiate the FD-P group from the ECP group. The high-density cholesterol levels in patients with ECP were significantly lower than those in AP-P. In addition, the combination of total and high-density cholesterol levels, BT-PABA test, and elastic score has a higher area under the curve value (0.708) of patients with ECP than in the other groups. CONCLUSIONS: The combination of high-density cholesterol levels, elastic score, and severity of exocrine pancreatic dysfunction may be useful for a predictive factor for patients with ECP.

Trypsin may be associated with duodenal eosinophils through the expression of PAR2 in early chronic pancreatitis and functional dyspepsia with pancreatic enzyme abnormalities.

BACKGROUND: Early chronic pancreatitis (ECP) has been reported to advance into chronic pancreatitis, it may be critical to differentiate the pathophysiology of ECP and functional dyspepsia (FD) in patients with pancreatic enzyme abnormalities (FD-P). This study aimed to clarify differences in the pathophysiology of ECP and FD-P and to determine whether duodenal inflammatory responses in the two diseases were associated with protease-activated receptor (PAR) 2, as the trypsin receptor. METHODS: Eighty patients who presented with FD-P and ECP were enrolled. In duodenal specimens, PAR2 mRNA levels were determined using real-time PCR. Using immunostaining, CD68-, GLP-1-, PRG2-, and CCR2-positive cells, tight junction proteins, and PAR 2 were evaluated. RESULTS: There were no significant differences in clinical symptoms and gastric motility between ECP and FD-P patients. The CD68-positive cells infiltrations and occludin expression levels in the duodenal mucosa of patients with FD-P were significantly (p<0.001 and p = 0.048, respectively) lower than those in patients with ECP. Although serum trypsin levels in ECP and FD-P patents were significantly (p<0.05 and p<0.001, respectively) associated with duodenal eosinophils counts, elevated trypsin levels were not significantly associated with degranulated eosinophils, occludin, claudin-1 and ZO-1 expression levels in the duodenum of either group. PAR2 mRNA levels were increased in the duodenum of patients with ECP and FD-P. PAR2 was localized in the epithelial cells of the duodenal mucosa and the surface of degranulated eosinophils in ECP and FD-P patients. CONCLUSIONS: Elevated trypsin levels might be partly associated with duodenal inflammatory responses through PAR2-related degranulated eosinophils and the reduction of occludin in patients with ECP and FD-P.

Transdermal treatment with tulobuterol increases isometric contractile properties of diaphragm muscle in mice.

Clinically, patients suffering from bronchial asthma are often treated transdermally with tulobuterol patches to dilate the bronchi. Tulobuterol, a synthetic beta(2) agonist, is also thought to act as a diaphragm muscle contractor, like other beta(2) sympathomimetic drugs. However, it has not been clarified that transdermal treatment with tulobuterol influences diaphragm muscle contractility. We therefore examined its effects on contractile properties of such muscles obtained from BALB/c mice. Two systems, a tulobuterol incubation group (in vitro) and a tulobuterol transdermal treatment group (in vivo), were employed. In both groups, the contractile properties of the dissected diaphragm muscles were measured by field stimulation in an organ bath. In the incubation group, the diaphragm muscle of untreated mice was incubated in an organ buffer at 10(-7), 10(-6), or 10(-5) M tulobuterol for 1 hr and then measured for contractility. Tulobuterol significantly increased force-frequency curves at a concentration of 10(-5) M at 1 (p < 0.01), 30, 50, 70, 100, and 120 Hz (p < 0.05, each) compared with the values at 0 M. In the transdermal treatment group, the diaphragm muscle was dissected from animals at 1, 4, 8, 12, or 24 hrs after treatment and measured for contractility, showing that the force-frequency curves were significantly increased and maintained from 4 to 24 hrs (each p < 0.01 as compared with the sham-treated group). We suggest that transdermal tulobuterol treatment in case of bronchial asthma is useful not only for bronchial dilatation, but also for increasing diaphragm muscle contractility.