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Biomedical subjects

Y Tando

Publications and source records attributed to Y Tando.

16 recordsLinked to original sources

Caerulein-induced NF-kappaB/Rel activation requires both Ca2+ and protein kinase C as messengers.

The eukaryotic transcription factor NF-kappaB/Rel is activated by a large variety of stimuli. We have recently shown that NF-kappaB/Rel is induced during the course of caerulein pancreatitis. Here, we show that activation of NF-kappaB/Rel by caerulein, a CCK analog, requires increasing intracellular Ca2+ levels and protein kinase C activation. Caerulein induces a dose-dependent increase of nuclear NF-kappaB/Rel binding activity in pancreatic lobules, which is paralleled by degradation of IkappaBalpha. IkappaBbeta was only slightly affected by caerulein treatment. Consistent with an involvement of Ca2+, the endoplasmic reticulum-resident Ca2+-ATPase inhibitor thapsigargin activated NF-kappaB/Rel in pancreatic lobules. The intracellular Ca2+ chelator TMB-8 prevented IkappaBalpha degradation and subsequent nuclear translocation of NF-kappaB/Rel induced by caerulein. BAPTA-AM was less effective. Cyclosporin A, a Ca2+/calmodulin-dependent protein phosphatase (PP2B) inhibitor, decreased caerulein-induced NF-kappaB/Rel activation and IkappaBalpha degradation. The inhibitory effect of bisindolylmaleimide suggests that protein kinase C activity is also required for caerulein-induced NF-kappaB/Rel activation. These data suggest that Ca2+- as well as protein kinase C-dependent mechanisms are required for caerulein-induced NF-kappaB/Rel activation.

Animals↗

Study on pancreatic insufficiency (chronic pancreatitis) and steatorrhea in Japanese patients with low fat intake.

The incidence of steatorrhea is said to be lower and its grade milder in Japanese because their fat intake is lower than that of Europeans and Americans. Failure to take this into account creates difficulties when attempting to compare data on pancreatic exocrine insufficiency in different countries. The authors examined the incidence and grade of steatorrhea in Japanese chronic pancreatitis (CP) patients whose daily fat intake was <40 g (25 patients) or > or =40 g (35 patients). In addition, 23 CP patients with steatorrhea and daily fecal fat excretion > or =5 g were given a pancreatic enzyme preparation at a dose 3-8 times higher than the usual dose to investigate its effect on fecal fat excretion. Among CP patients whose fat intake was <40 g, the incidence of fecal fat excretion <5 g was 56% and that of fecal fat excretion > or =10 g (severe steatorrhea) was 8%. In CP patients whose fat intake was > or =40 g, the incidences were 27.9 and 34.9%, respectively; a significant increase in the number of affected patients was noted when fat intake was > or =40 g. The fat absorption rate was 76.2% among patients whose fat intake was <40 g and 77.8% among patients whose fat intake was > or =40 g, revealing no significant difference between the two groups. The proportion of CP patients whose fat absorption rate < or =80% was 32% at a fat intake <40 g and 39% at a fat intake > or =40 g, revealing no significant difference between the two groups.

Adult↗

A case of acromegaly accompanied by adrenal preclinical Cushing's syndrome.

We encountered a 58-year-old woman with acromegaly accompanied by a cortisol-secreting adrenal tumor without clinical features of hypercortisolism. The simultaneous occurrence of these two endocrinopathies in one individual is extremely rare. She was diagnosed as having diabetes mellitus 8 years ago. Afterwards, in spite of insulin therapy, her hyperglycemia could not be well controlled. Her acromegaly and preclinical Cushing's syndrome were histopathologically proven to be due to a pituitary adenoma and an adrenocortical adenoma, respectively. Successful treatment for these endocrinopathies resulted in greatly improved blood sugar control because of a reduction in insulin resistance. In this case of preclinical Cushing's syndrome, replacement therapy with glucocorticoid was able to be discontinued at only 8 weeks after adrenalectomy, so that the period of necessary replacement was much shorter than that for overt Cushing's syndrome. This is the first report describing insulin resistance before and after treatment in a case of acromegaly accompanied by adrenal preclinical Cushing's syndrome.

Acromegaly↗

Pancreatic dysfunction and treatment options.

Pancreatic steatorrhea and pancreatic diabetes are the dominant symptoms of patients in the decompensated stage of chronic pancreatitis (CP). In this stage, the nutritional state is greatly disturbed and hypoglycemia and labile infection are involved. Pancreatic enzyme replacement therapy is the principal treatment method for pancreatic steatorrhea. Before initiating this therapy, dietary fat intake must be determined and pancreatic lipase and bicarbonate secretion function must be evaluated. Upper small intestinal pH is regulated by gastric acid secretion, and abnormal gastric emptying changes lipolysis. In addition, precipitation of bile acids in the upper small intestine and ileal brakes due to undigested fats and carbohydrates must be considered. Porcine pancreatin, bacterial lipase, and acid-resistant fungal lipase are used as enzymes for replacement therapy. Conventional, entero-coating, and enteric-coated microsphere preparations of porcine pancreatin are available for treatment and are formulated to protect against gastric acids, to dissolve enzymes at optimum pH, and to be emptied simultaneously with food from the stomach. Gastric acid secretion suppressants, such as H2 blockers or a proton pump inhibitor, can also be used concomitantly with pancreatin preparations. In consideration of both strengths and weaknesses of these preparations, types and dosages of enzyme replacement therapy should be carefully prescribed, and fecal fats should be examined repeatedly by a simple and rapid method during treatment. Attention should also be paid to changes in body weight and nutritional indices (e.g., nutritional parameters, fat-soluble vitamins). The relationship between carbohydrate maldigestion/malabsorption in CP patients and treatment of pancreatic diabetes are topics for future research.

Chronic Disease↗

Near-infrared spectrometry analysis of fat, neutral sterols, bile acids, and short-chain fatty acids in the feces of patients with pancreatic maldigestion and malabsorption.

CONCLUSION: Near-infrared spectrometry is a new, rapid, and accurate method for measuring fecal fat that does not require a great deal of chemical knowledge and that can be used by anyone. This method is considered indispensable for the diagnosis of pancreatic steatorrhea and treatment follow-up. METHODS: Fecal fats (GLC method, van de Kamer method), neutral sterols (GLC method), bile acids (GLC method) and short-chain fatty acids (HPLC method) were assayed by the respective conventional methods in 120 subjects, including patients with pancreatic dysfunction, and the results were compared with the those obtained by near-infrared spectrometry. The correlations between fecal fat excretion measured by the GLC method (x) and van de Kamer method (x) and by near-infrared spectrometry (y) were expressed by y = 1.10x - 0.16 (r = 0.949, P < 0.01) and y = 0.750x + 1.654 (r = 0.930, p < 0.01), respectively. RESULTS: The sensitivity and specificity of near-infrared spectrometry for fecal fats were 94.9 and 98.2%, respectively, when compared with the GLC method, and 87.5 and 90.0%, respectively, when compared with the van de Kamer method. In contrast, near-infrared spectrometry was not nearly as accurate as the conventional methods for determining neutral sterols, bile acids, and short-chain fatty acids.

Bile Acids and Salts↗

Can pancreatic steatorrhea be diagnosed without chemical analysis?

CONCLUSION: Visual observation of feces, considering fecal output, is considered to be an excellent method of detection of steatorrhea when judged by experienced doctors. METHODS: Feces from 192 patients with untreated chronic pancreatitis or under pancreatic enzyme therapy were investigated. Feces were collected for three consecutive days and homogenized with water. Fecal samples were freeze-dried and analyzed for fatty acids by gas chromatography (GLC). The quantity of fat was calculated from the amount of fatty acid to obtain daily fecal fat excretion. Comparison of GLC method with van de Kamer method gave a significant (p < 0.01) positive correlation with correlation coefficient of 0.916 (n = 38). Steatorrhea was defined as fecal fat excretion exceeding 5 g/d. Mild steatorrhea was defined as 5-10 g/d, and severe steatorrhea as more than 10 g/d. RESULTS: Three visual identification items were used to consider fecal output exceeding 200 g/d: fecal fat concentration exceeding 4%, appearance, and odor. The results were compared with the results from GLC method. Detection of steatorrhea by means of visual properties was the most accurate, and correlation coefficient was 0.843 (p < 0.01) by Spearman's rank correlation test. This detection method was also significantly effective for differentiation of normal stool from mild and severe steatorrhea. The sensitivity and specificity were 89.3 and 91.1%, respectively, indicating a favorable result.

Celiac Disease↗

Serum fatty acid composition in normal Japanese and its relationship with dietary fish and vegetable oil contents and blood lipid levels.

A survey was conducted on 110 normal Japanese adults (55 men and 55 women) to determine their caloric intake, dietary fat content and its origin (animal, plant, or marine). In addition, their blood lipid levels and fatty acid compositions were examined. Men in their 30s-50s consumed 2,600-2,800 calories and 60 g of fats, while women in the same age range consumed 2,000-2,200 calories and 52-58 g of fats. In both sexes, caloric, fat, and cholesterol intakes were lower for those in their 60s but protein and crude fiber consumption remained generally unchanged. When the dietary fats were classified according to origin, men and women in their 30s were found to consume less oil of marine origin. This appeared to be the result of a western style diet for Japanese adults in their 30s. Compared with men, women exhibited lower blood lipid levels. As age increased, the total cholesterol level of the blood rose in women. Thus the blood lipid level was generally equal in the two groups in their 60s. There was a positive correlation between the blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels and dietary consumption of fish oil. The marine/plant lipid ratio was positively correlated with the blood EPA/arachidonic acid ratio. Therefore, it was believed that the origin of the dietary fats consumed is a factor in determining the blood fatty acid profile. The linoleic acid (18:2), arachidonic acid (20:4), and 18:2 + 20:4 contents were negatively correlated to the total cholesterol level in the blood but positively correlated to the HDL-cholesterol level. Polyunsaturated fatty acids (18:2 + 20:4 + 20:5 + 22:6) were negatively correlated with the blood triglyceride level. From the findings presented above, we concluded that dietary fats not derived from animal sources should be classified into fish and vegetable oils to evaluate their dietary significance. We also noted that Japanese in their 30s consume less fish oil, indicating the western trend in their dietary lipid consumption.

Adult↗

[An analysis on fat digestion in the upper small intestine after intragastric infusion of a test meal in patients with exocrine pancreatic insufficiency].

To clarify the mechanism of the fat maldigestion in 9 patients with exocrine pancreatic insufficiency, lipase activities, pH, and micellar lipids in the upper small intestinal contents were studied. The upper small intestinal pH was slightly less in patients with exocrine pancreatic insufficiency than in healthy controls. Lipase activities and micellar lipids were significantly reduced in patients with exocrine pancreatic insufficiency compared with in healthy controls. There was a significant correlation between serum cholesterol and micellar cholesterol concentrations. The results suggest that there is maldigestive state in the digestion-absorption process in patients with exocrine pancreatic insufficiency due to insufficiency of lipase secretion and that insufficiency of lipase secretion disturbs hydrolysis of triglyceride and prevents micelle formation and leads to reduced uptake of cholesterol into micellar phase and it is reflected in serum cholesterol.

Adult↗

Octreotide decreases biliary and pancreatic exocrine function, and induces steatorrhea in healthy subjects.

A somatostatin analogue (SMS-201-995, hereinafter "octreotide") was s.c. administered to 5 healthy subjects under consecutive dripping of CCK-PZ (cholecystokinin-pancreozymin) and secretin (0.01 CHR U/kg/minutes), after inserting a Dreiling double tube into Treitz's ligament. Bile acid concentration, and bicarbonate and lipase excretions in duodenal juice were determined every 10 minutes up to 120 minutes and compared with controls. Moreover, octreotide (100 micrograms) was s.c. administered to 5 healthy subjects 30 minutes before meals for 7 days. Fecal fat and bile acid excretions before and after administration were determined. Bile acid concentration, and bicarbonate and lipase excretions in the octreotide group decreased to 1/3-1/4 that of controls. Bile acid concentration became 0 mM for 60 minutes. Fecal fat excretion increased; obvious steatorrhea occurred in 2 cases. Fecal bile acid excretion decreased to about 1/4. These results suggest that decreases in bile acid secretion should be considered, as well as pancreatic lipase and bicarbonate secretions, when fatty stool occurs after octreotide administration.

Adult↗

Bile acid malabsorption as a cause of hypocholesterolemia seen in patients with chronic pancreatitis.

A determination of caloric consumption based on a dietary survey table, fat and cholesterol intake, and analyses of fecal fatty acids and neutral sterols, and bile acid analysis (gas chromatographic method) were conducted on 33 subjects (including 17 patients with chronic pancreatitis and 16 normal controls). The factors related to hypocholesterolemia in chronic pancreatitis (CP) patients were investigated and the following conclusions were obtained: (1) The total caloric intake and fat consumption by the CP patients were significantly lower with the exception of cholesterol consumption. (2) Significant increases were noted in fecal fat, neutral sterols, and bile acid excretion by the CP patients. (3) A significant positive correlation was noted between the total cholesterol and body mass index (BMI), reaffirming that the cholesterol level can be used as an indicator of nutritional status. (4) A significant negative correlation was noted between the serum total cholesterol and fecal bile acid excretion. These findings indicate that CP patients suffer from neutral sterol malabsorption, in addition to dietary fat maldigestion and bile acid malabsorption. Furthermore, bile acid malabsorption is cited as a factor in the development of hypocholesterolemia in CP patients.

Adult↗

Effect of omeprazole on changes in gastric and upper small intestine pH levels in patients with chronic pancreatitis.

Gastric and upper small intestine pH levels were measured continuously over 24 hours in patients with chronic pancreatitis, and values obtained before and after the administration of omeprazole were compared. Additionally, omeprazole was administered for 2 weeks and the fecal excretion of fat was compared before and after drug therapy. Postprandial gastric pH levels, initially 2.9 to 3.2, increased by 1.6 to 2.1 after treatment. Postprandial upper small intestine pH levels, initially 5.1 to 5.5, increased by 0.7 to 1.0. The lowest pH value of the upper small intestine was 2.2 to 2.4 postprandially; this was increased by > 1.0 after omeprazole, and the amplitude of pH variation was reduced. The cumulative proportions of intraintestinal pH strata of < or = 3, < or = 4, or < or = 5, and higher, initially being 16.4% to 17.1%, 27.4% to 31.7%, and 52.6% to 57.8%, respectively, were remarkably improved after drug treatment. Gastric pH and upper small intestine pH levels showed a positive correlation; an increase in gastric pH levels by 2 corresponded to an increase in small intestine pH levels by 1. After omeprazole administration, mean fecal excretion of fat was decreased to 4.1 +/- 2.6 g/d (range, 1.1 to 9.8 g/d) from 6.5 +/- 3.9 g/d (range, 1.6 to 13.5 g/d). Decreases in excretion of fat averaged 3.4 g/d (range, 2.2 to 4.5 g/d) in patients with steatorrhea. It was concluded that steatorrhea due to chronic pancreatitis can be improved to some extent by improving upper small intestine pH levels following the elevation of gastric pH levels after administration of omeprazole.

Adult↗

Faecal triglycerides and fatty acids in the differential diagnosis of pancreatic insufficiency and intestinal malabsorption in patients with low fat intakes.

To investigate possible parameters for the differential diagnosis of steatorrhoea in patients with low fat intakes, faecal specimens were analysed from 15 patients with steatorrhoea due to chronic pancreatitis and seven patients with steatorrhoea due to intestinal malabsorption. The fat intakes of the patients ranged from 30.1 to 60 g, less than the average in American and European patients. The group with pancreatic steatorrhoea showed a significantly lower faecal output than the group with intestinal steatorrhoea but the two groups did not differ significantly in their total faecal fat excretion or concentration. The percentage triglycerides and the molecular ratio of triglycerides to fatty acids in the faeces were significantly higher (P < 0.01) in the group with pancreatic steatorrhoea than in those with intestinal steatorrhoea. The molecular percentage ratio of triglycerides to fatty acids was 6.8 +/- 2.2 for the chronic pancreatitis group and 2.4 +/- 1.0 for the intestinal malabsorption group; while the respective faecal hydroxy fatty acid contents were 3.1 +/- 3.6% and 10.1 +/- 3.3% (means +/- SDs). These latter two parameters appeared to be the most valuable for distinguishing the two forms of steatorrhoea.

Adult↗

Fat-soluble vitamins in patients with chronic pancreatitis (pancreatic insufficiency).

The fat-soluble vitamin contents in the blood (vitamins A, D, E, and K) were determined in 12 patients with chronic pancreatitis (exocrine pancreatic insufficiency) and in 20 healthy adults by the HPLC and CPBA methods. In addition, 9 g (3 g x 3 times) of high potency pancreatin was given to 11 patients with chronic pancreatitis (CP) for approximately 1 month and changes in the blood fat-soluble vitamin levels were evaluated before and after the treatment. The major component of vitamin E was alpha-tocopherol. The mean alpha-tocopherol level in normal individuals was 0.97 mg/dl, while it was significantly reduced in CP patients (p < 0.01). The vitamin A, D, and K levels had also been reduced in patients with CP, but the differences were not significant (although some patients in this group exhibited significant reductions from the levels of normal individuals). Only the blood vitamin E level showed a significant correlation with the fecal fat excretion or the fat absorption rate. None of the patients with CP exhibited an overt fat-soluble vitamin deficiency (i.e., the deficiency of fat-soluble vitamins was at a subclinical level). These results indicated that CP patients suffer from a latent fat-soluble vitamin deficiency and that the vitamin E level is closely related to a dysfunction of fat digestion. It was suggested that the dietary intake of each fat-soluble vitamin should be evaluated further.

Adult↗

Study of gastric emptying in patients with pancreatic diabetes (chronic pancreatitis) using acetaminophen and isotope.

The gastric emptying function tests were carried out in eight patients with pancreatic diabetes, who were classified into two groups according to the coefficient of variation in the R-R interval in ECG (C.V. R-R) on the normal subjects: < or = the mean - 2SD (the autonomic nerve dysfunction group: AND+ group) and > the mean - 2SD (the autonomic nerve normal group: AND- group). Both the gastric emptying of liquid food by the acetaminophen method and that of solid food by the isotope method were significantly reduced in the AND+ group than in the AND- and normal groups. In addition, a significant correlation was found between the C.V. R-R and the serum acetaminophen concentration (a 45 min value) and the % gastric retention of isotope (a 120 min value). The above results demonstrated that even pancreatic diabetes might be complicated by gastroparesis diabeticorum among autonomic nerve dysfunction. There was a close relation of delayed gastric emptying to the C.V. R-R in ECG or an index of the vagus nerve function.

Acetaminophen↗

Meal-related changes in plasma CCK bioactivity in patients with chronic pancreatitis.

In order to clarify whether there is a negative feedback mechanism for CCK secretion, we investigated plasma CCK bioactivity in patients suffering from chronic pancreatitis (CP) according to the characteristics of their pancreatic disease. Basal, meal-stimulated, and integrated release of plasma cholecystokinin (CCK) bioactivity was measured in 24 patients with CP and in 12 healthy controls. The values obtained were compared between the healthy control group and the CP group, and between subgroups of CP patients established on the basis of the presence/absence of several parameters: abnormal gastric emptying, abdominal pain, steatorrhea, pancreatic calcification, insulin-requiring diabetes mellitus, and impairment of pancreatic exocrine functions as indicated by secretin test. A bioassay method using pancreatic acini was used to measure plasma CCK bioactivity. In the control group, plasma CCK bioactivity increased from a basal value of 1.6 +/- 0.7 pmol/L to a maximal increase of 6.6 +/- 4.1 pmol/L, and the integrated CCK release following a test meal was 37.7 +/- 19.3 pmol/L.150 min. In the CP group, plasma CCK bioactivity increased from 1.6 +/- 0.9 pmol/L to a maximal increase of 8.2 +/- 8.7 pmol/L, and the integrated release of CCK was 43.0 +/- 37.7 pmol/L.150 min. None of the differences between them were significant. No significant differences in basal value, maximal increase, or integrated plasma CCK release were noted according to any of the parameters of the CP patients and the control group. Nor was there any correlation between impairment of pancreatic exocrine function and plasma CCK bioactivity. These results provide no evidence of a negative feedback mechanism between pancreatic exocrine dysfunction and CCK secretion.

Adult↗