Yasuyuki Nakae

Effects of aging and gastric lipolysis on gastric emptying of lipid in liquid meal

Abstract: Lipid delays gastric emptying, and aging is associated with changes in gastric motor function and transit. However, little is known about the effect of lipid on gastric emptying time in the elderly. To determine the effect of aging on lipid gastric emptying, we used electrical impedance tomography (EIT) to study gastric emptying of liquid meals with or without lipid in five young (23.0 ± 0.6 years, mean ± SEM) and six elderly (73.3 ± 1.6 years) healthy male volunteers. These subjects drank 400 ml of non-lipid soup (triglycerides, 0 g) or lipid soup (triglycerides, 24.6 g) in liquid test meals. To study the effect of lipolysis in the stomach, a liquid test meal containing 240 mg of lipase in the lipid soup was also administered. Plasma cholecystokinin (CCK) concentration was measured by specific radioimmunoassay before and 30 min after the ingestion of a test meal. The gastric emptying time of the lipid soup was longer in the elderly than in the young subjects, and the time was significantly longer for lipid soup than for non-lipid soup (P < 0.05) in both the young and elderly subjects. Gastric emptying time for non-lipid soup was not significantly different between the elderly and young subjects. The administration of lipase shortened the gastric emptying time for lipid in both the elderly and the young subjects. Basal CCK concentration was significantly higher in the elderly than in the young subjects. However, there was no relationship between gastric emptying time and plasma CCK concentration after the ingestion of a test meal in the subjects overall. In conclusion, the delaying effect of lipid on gastric emptying is increased in the elderly, and the administration of lipase accelerates the emptying of lipid from the stomach.

Activation of trypsinogen in experimental models of acute pancreatitis in rats

Trypsinogen activation peptide (TAP) concentration and α2-macroglobulin-trypsin complex (α2M-T) activity were measured in two experimental models of acute pancreatitis in rats to evaluate the significance of activation of trypsinogen in acute pancreatitis. TAP concentration and α2M-T activity in serum rose significantly in trypsin-taurocholate-induced hemorrhagic acute pancreatitis, while in cerulein-induced edematous acute pancreatitis they did not rise in spite of a similar increase in immunoreactive trypsin. When rats in trypsin-taurocholate-induced pancreatitis were treated by protease inhibitor (FUT-175; nafamostat mesilate; FUT group), α2M-T activity in serum was significantly lower than that in nontreated controls (mean ± SEM, 20.8 ± 1.43 U/L in the FUT group vs 79.1 ± 24.5 in controls; p < 0.01). The survival rate at 24 h was significantly improved in the FUT group compared with the controls (70 vs 43%; p < 0.05). The increase in TAP concentration in the FUT group was similar to that in controls. The TAP concentration in pancreatic tissue at 24 h was significantly (p < 0.01) lower in the survival group (7.8 ± 0.8 ng/ml) than in the lethal group (25.9 ± 3.7 ng/ml). Activation of trypsinogen and its subsequent enzyme activity play an important role in the evolution of severe acute pancreatitis.

Evaluating exocrine function tests for diagnosing chronic pancreatitis

To evaluate the effectiveness of exocrine function tests in diagnosing chronic pancreatitis (CP), we compared the sensitivity and specificity of duodenal intubation with tubeless tests. While the secretin test (ST) was necessary to diagnose CP, especially in noncalcified CP, and tubeless tests demonstrated insufficient sensitivity to diagnose CP, the combination assay of tubeless tests was specific enough to diagnose severe exocrine dysfunction. Our studies found the sensitivity of secretin testing to diagnose definite CP to be 87%. In patients with probable CP, 60% had mild exocrine insufficiency and 40% had normal function. The false-positive rate of the ST results in nonpancreatic diseases, except diabetes mellitus, was 5%. The correlation between morphological changes in endoscopic retrograde pancreatography (ERP) and exocrine function evaluated by ST was 74%. In patients with calcified CP, 81 % had parallel results between ERP and the ST, but in non- calcified CP, 47% had parallel results. In patients with severe or moderate exocrine insufficiency demonstrated by ST, abnormally low levels were observed in 63% by N-benzoyl-L-tyro- syl-p-aminobenzoic acid (BT-PABA) test, 61% by fecal chymotrypsin test (FCT), and 44% by pancreatic amylase (PA). In patients with normal exocrine function demonstrated by ST, abnormally low levels were observed in 28% by BT-PABA test, 28% by FCT, and 10% by PA. A combination assay of BT-PABA test, FCT, and PA improved the specificity for diagnosing CP but not the sensitivity.

SMALL BOWEL TRANSIT TIME AND COLONIC FERMENTATION IN YOUNG AND ELDERLY WOMEN

Small bowel transit time (SBTT) in 15 young and 13 elderly women was assessed by measuring breath hydrogen concentrations after they had consumed a solid test meal. The meal consisted of 200 g cooked rice, 50 mlmiso (made from fermented soy bean curd) soup, a boiled egg, and 95.5 g of cooked soy beans with mixed vegetables. This meal provided 17 g protein, 14.1 g fat, 92.9 g carbohydrate, 7 g dietary fiber, and 565 kcal total energy. The SBTT, calculated by a 3 ppm increase in breath hydrogen, was 19±14.9 (mean±SE) min in the young and 188.1±16.8 min in the elderly group; the difference was not significant. Breath hydrogen levels, however, were higher in the young than in the elderly group (39.1±6.3 ppm, vs 22.2±4.3 ppm,P<0.05). There was an initial peak of hydrogen concentration, reached almost immediately after the ingestion of the meal, and then a decline to baseline within 60 min. This initial peak was not as pronounced in the elderly subjects. A second peak, indicating the entry of the test meal into the cecum, was more pronounced in the young than in the elderly group. SBTT did not differ significantly between the two groups, but colonic fermentation was more pronounced in the young, both in the fasting and the postprandial state.

Effect of a new inhibitor of type II phospholipase A2 on experimental acute pancreatitis in rats.

The catalytic activity of type II phospholipase A2 (PLA2) in blood has been reported to increase in acute pancreatitis and to reflect the severity of pancreatitis. In this study, we evaluated the effects of a new inhibitor of type II PLA2, S5920/LY315920Na, on trypsin-taurocholate-induced pancreatitis in rats. Hemorrhagic pancreatitis was induced by an infusion of a mixture of trypsin and taurocholate into the pancreatic duct. S5920/LY315920Na was administered subcutaneously at 0 h and 3 h after the induction of pancreatitis. Survival rates for 24 h in rats treated with 0.1 and 1 mg/kg of S5920/LY315920Na were significantly higher than that in untreated rats (71 and 86% vs. 14%). Serum levels of amylase and lipase in rats treated with 1 mg/kg of S5920/LY315920Na were significantly lower than those in untreated rats (amylase, 6,903 vs. 32,516 U/L; and lipase, 514 vs. 6,710 U/L) at the time of death or 24 h after the induction of pancreatitis. Plasma levels of S5920/LY315920Na were enough to inhibit catalytic activity of PLA2 in plasma for 9 h. A new inhibitor of type II PLA2, S5920/LY315920Na, inhibited catalytic activity of PLA2 and improved the survival rate in experimental hemorrhagic pancreatitis in rats.

Pancreatic stone protein and lactoferrin in human pancreatic juice in chronic pancreatitis.

Lactoferrin and pancreatic stone protein (PSP) are thought to be closely related to pancreatic stone formation in chronic pancreatitis. However, the results reported so far have not been conclusive. To reevaluate the pathological importance of PSP in chronic pancreatitis, compared to lactoferrin, levels of PSP were determined by applying an immunoassay specific to PSP to pure pancreatic juice taken from a total of 52 patients. The patients consisted of 16 controls, 19 chronic pancreatitis patients (13 noncalcified and 6 calcified), and 17 probable cases of pancreatitis. The monoclonal antibody PSP antagonist used in the study recognizes both forms of the protein, PSP S1 and S2–5, with equal effectiveness. No significant reduction of PSP was observed in either calcified (mean ± SEM, 111 ± 30 μg/mg and 24 ± 3 μg/mg protein) or noncalcified (305 ± 133 and 97 ± 47) chronic pancreatitis patients compared with controls (85 ± 23 and 34 ± 16). PSP levels did not decrease, at least not in the complete forms of the protein found in chronic pancreatitis. PSP antibody and assay results indicated that a reduction of PSP S2–5 alone could not be ruled out in chronic pancreatitis either.

Serum pancreatic stone protein in pancreatic diseases.

SummarySerum pancreatic stone protein (PSP) was determined in sera of pancreatic and nonpancreatic diseases using enzyme immunoassay specific to human PSP to study the diagnostic and pathophysiological significance of PSP. Serum PSP in acute pancreatitis (mean±SD=1075.4±2849.1 ng/mL,n=33) was significantly higher than that in controls (78.6±31.8 ng/mL,n=37,p<0.01), chronic pancreatitis (156.8±82.8 ng/mL,n=32,p<0.05), and pancreatic cancer (148.468.8 ng/mL,n=26,p<0.05). No significant difference was found between noncalcified and calcified chronic pancreatitis. Serum PSP levels were significantly higher in chronic renal failure under hemodialysis (1796.0±1492.9 ng/mL) than in other diseases such as peptic ulcer, liver cirrhosis, gallstone, and diabetes mellitus. Low but significant correlation was obtained between serum PSP and serum immunoreactive trypsin (r=0.22,p<0.05). Increased serum PSP levels in acute pancreatitis and chronic renal failure suggest that serum PSP levels reflect reflux from pancreatic secretion, release from damaged pancreatic acinar cells, or retention in circulation, and can be useful for diagnosis of acute pancreatitis, but not chronic calcified pancreatitis.

Association of fasting breath nitrous oxide concentration with gastric juice nitrate and nitrite concentrations and Helicobacter pylori infection.

Fasting breath nitrous oxide (N2O) concentration was determined in relation to pH, nitrate (NO3−) and nitrite (NO2−) concentrations in gastric juice, and Helicobacter pylori infection in 86 successive patients. N2O was measured with an infrared-photoacoustic analyzer. NO3− and NO2− were measured using the Griess reaction. Fasting breath N2O concentration in controls (87 ± 21 ppb) was not significantly different from that in patients with gastric ulcer or other gastric lesions. Breath N2O was significantly correlated with gastric NO3−(P < 0.01) and was higher in patients with elevated gastric NO2− (246 ± 87 ppb) than in patients without NO2− (75 ± 13 ppb). Breath N2O did not differ significantly between subjects who were positive or negative for H. pylori. In conclusion, fasting breath N2O concentration is in some manner related to intragastric NO3− and NO2− concentrations. The possible use of measuring breath N2O as predictors of cancer needs further research.

Chronic Pancreatitis: Overview of Medical Aspects

Based primarily on our experience, we review current problems on etiology, pathogenesis, classification, diagnosis, and treatment of chronic pancreatitis. Much of the confusion and difficulty associated with chronic pancreatitis originates from the relative inaccessibility of this organ. A lack of specific and sensitive markers that are suitable for the follow-up of a long natural course of chronic pancreatitis also hinders our understanding of this disease. The resolution of the present imaging tests, even by the latest technology, is not good enough to detect early changes of the pancreas. In the past 10 years, several subgroups of patients with alcoholic and idiopathic pancreatitis have been identified based on the long-term follow-up study. Pain disappeared spontaneously in many patients during the course of the disease, but its mechanism is still poorly understood. Removal of pancreatic stones and protein plugs by chemical, endoscopic, or extracorporeal shock-wave therapy has been tried with some success, but their clinical values remain to be established. Attempts have been made to understand the etiology and pathogenesis of chronic pancreatitis at molecular levels. This approach, together with a prospective follow-up of patients, will improve our understanding on chronic pancreatitis.

The effect of chronic exercise on the rat pancreas

SummaryBackground. We recently demonstrated that chronic physical exercise increases pancreatic protein content and basal amylase secretion. It is unknown whether chronic exercise causes hypertrophy or proliferation of pancreatic acinar cells. Methods. Female F344 rats (age, 6 wk) were divided into control (n= 7) and exercise (n=6) groups. Food consumption was matched between the 2 groups. Rats in the control group were kept sedentary. Rats in the exercise group were exercised for 60 min, 5 d/wk during the experiment. After 8 wk, the pancreas and hindlimb muscles were rapidly excised and weighed. Protein and DNA content and enzyme activity in pancreatic tissue were measured. Pancreatic tissues from control and exercised rats were also prepared for transmission electron microscopy. Results. Inhibition of growth and hypertrophy of hindlimb muscles were exhibited by the exercise group. In the exercise group, pancreatic wet weight, protein content, and amylase and lipase activities, but not DNA content, were significantly higher than those in the control group. Electron micrographs clearly revealed that acinar cells were hypertrophied and zymogen granules were increased in number in exercised rats.Conclusion. Chronic endurance exercise increases pancreatic weight, protein content and enzyme activity through hypertrophy of acinar cells.