Elevated fasting cholecystokinin levels in pancreatic exocrine impairment: evidence to support feedback regulation

Previous studies have suggested that intraduodenal protease suppression of pancreatic exocrine secretion may be mediated through cholecystokinin (CCK) release. Our study compares basal plasma immunoreactive CCK concentrations in normal human subjects with those obtained in patients with chronic pancreatitis. Fasting plasma samples were collected from 18 normal subjects and from 18 patients with chronic pancreatitis. Eight patients had mild to moderate pancreatic exocrine impairment, and 10 had severe exocrine insufficiency. Venous plasma immunoreactive CCK concentrations were measured with two distinct peptide region-specific antibodies. Basal plasma CCK concentration in controls was 14.3 +/- 1.3 fmol/ml (mean +/- SEM), a value significantly less than that obtained in all patients with chronic pancreatitis, 30.1 +/- 4.0 fmol/ml (p less than 0.001). Patients with mild to moderate impairment had a fasting plasma CCK concentration of 32.8 +/- 7.9 fmol/ml (vs. control p less than 0.01), and those with severe disease 27.9 +/- 3.6 fmol/ml (vs. control p less than 0.001). In five patients with mild to moderate impairment of exocrine function and pancreatic extract-responsive abdominal pain, there was a 39 +/- 11% decrease in basal CCK levels during extract therapy (p less than 0.05). Results of this study indicate that pancreatic exocrine impairment is associated with elevated basal CCK levels, which may reflect a failure to provide feedback downmodulation of CCK release.     

Hypotrypsinaemia in diabetes mellitus.

Plasma trypsin concentrations were measured in 403 fasting diabetics and 106 healthy controls. Basal trypsin concentrations in the normal subjects were 88 +/- 6 ng/ml (mean +/- S.E.M.). Mean plasma trypsin concentrations in diabetics treated with diet alone (n = 74) were 45 +/- 2 ng/ml, while in a group of young (less than 35 years, n = 88) insulin-dependent diabetics, they were very low at 29 +/- 2 ng/ml and these levels were inversely related to insulin dosage. The findings may help in the understanding of the pathophysiological changes in the exocrine pancreas in the diabetic state and may also shed some light on the physiological interrelationship between the endocrine and exocrine pancreas.     

Kinetics and dynamics of triamterene at steady-state in patients with cirrhosis

Triamterene is a potassium-sparing diuretic used in patients with cirrhosis for the treatment of ascites. It is extensively metabolized by the liver and is subject to an important first-pass effect after oral dosing. We examined the disposition and diuretic effect of triamterene after repeated oral administration (200 mg daily for 10 days) in 7 healthy controls and 6 patients with cirrhosis and ascites. In the controls the average plasma concentration of triamterene during a dosage interval was 45 +/- 8 ng/ml and that of hydroxy-triamterene sulfate, an active metabolite of triamterene, was 967 +/- 177 ng/ml. In the cirrhotics, the mean concentration of triamterene was 586 +/- 126 ng/ml (a 13-fold increase as compared with the controls) and that of hydroxy-triamterene sulfate was 747 +/- 502 ng/ml. Sodium excretion was correlated with hydroxy-triamterene sulfate levels in the controls (r = 0.81), but in the cirrhotics the diuretic response was correlated with basal sodium excretion (r = 0.86) and was not related to either triamterene or hydroxy-triamterene plasma concentrations. Our results indicate that chronic treatment with triamterene in patients with cirrhosis and ascites results in markedly elevated plasma levels, but these changes do not have a major influence on the magnitude of the diuretic response.     

Comparisons between absorption of vitamin E in patients with chronic pancreatitis and healthy controls: the bioavailability of vitamin E

The fasting serum levels of alpha-tocopherol were determined by high-pressure liquid chromatography in 13 patients with chronic pancreatitis of whom 7 were positive for pancreatic calcification (CCP) and 6, negative (NCP) and 10 healthy subjects. The fasting serum levels of alpha-tocopherol were significantly lower in patients with chronic pancreatitis (7.2 +/- 1.1 micrograms/ml for CCP and 7.9 +/- 0.6 for NCP) than in healthy subjects (11.3 +/- 0.7 micrograms/ml). Vitamin E absorption was determined in those with chronic pancreatitis and in healthy subjects after postprandial oral administration of 400 mg of vitamin E, using soft capsules which contained tocopherol nicotinate along with an appropriate amount of a suspension of an ester of fatty acids with glycerol and middle chain triacylglycerol. The mean absorption of vitamin E was 12.7 +/- 2.0 micrograms/ml X hr for healthy subjects, 9.1 +/- 3.1 micrograms/ml X hr for CCP and 13.0 +/- 2.7 micrograms/ml X hr for NCP, respectively. There was no significant difference in vitamin E absorption between patients with chronic pancreatitis and healthy subjects. Further, the rate of hydrolysis of tocopherol nicotinate did not significantly differ between healthy subjects and patients with chronic pancreatitis. It is of interest to note that vitamin E absorption in patients with chronic pancreatitis was increased by the postprandial use of an oily suspension type preparation of tocopherol nicotinate.     

Renal excretion of antidiuretic hormone in healthy subjects and patients with renal failure

Urinary clearance of antidiuretic hormone (ADH) has been measured under basal conditions and during intravenous administration of arginine vasopressin in ten healthy subjects, and only under basal conditions in 18 patients with chronic renal failure and seven patients with acute renal failure at the polyuric phase of the disease. In healthy subjects studied under conditions of mild water diuresis plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 3.3 +/- 0.36 pg/ml, 25.2 +/- 5.5 pg/min, 7.5 +/- 1.2 ml/min and 6.4 +/- 1.0% (means +/- SEM) respectively. When plasma ADH was raised to levels between 7 and 26 pg/ml during intravenous administration of the hormone, urinary excretion rate and urinary clearance of ADH increased. Tubular reabsorption of ADH did not reach a plateau but progressively increased in the range of plasma ADH studied. In patients with chronic renal failure, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 2.8 +/- 0.19 pg/ml, 9.4 +/- 2.0 pg/min, 3.4 +/- 0.6 ml/min and 10.0 +/- 2.9% (means +/- SEM) respectively. Urinary excretion rate and urinary clearance were significantly lower than in healthy subjects. In patients with acute renal failure, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 4.6 +/- 0.47 pg/ml, 52.8 +/- 15.8 pg/min, 9.5 +/- 2.7 ml/min and 24.9 +/- 4.4% (means +/- SEM) respectively. Urinary excretion rate and fractional clearance were higher than in healthy subjects and patients with chronic renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radioimmunoassay for human pancreatic secretory trypsin inhibitor: measurement of serum pancreatic secretory trypsin inhibitor in normal subjects and subjects with pancreatic diseases

A reliable radioimmunoassay (RIA) for human pancreatic secretory trypsin inhibitor (PSTI) has been developed. The method is highly sensitive (0.4 ng/ml), reproducible and specific. A good parallel relationship was observed between the standard curve and dilution curves for serum and urine. The PSTI bound to trypsin-alpha 2-macroglobulin complexes was found not to be immunoreactive, whereas a part of the psti-trypsin complex was immuno-reactive. In healthy individuals, serum PSTI level ranged from 5.4 ng/ml to 16.0 ng/ml, the average being 11.3 ng/ml (S.D. +/- 2.7). Elevated values were observed in patients with acute pancreatitis (highest value 3200 ng/ml), and in some patients with chronic relapsing pancreatitis.     

Urinary oxalate recovery after oral oxalic load: an alternative method to the quantitative determination of stool fat for the diagnosis of lipid malabsorption

Urinary oxalate concentrations were measured in 45 patients with quiescent Crohn's disease, four patients with chronic pancreatitis and five healthy subjects after a normal oxalate (150 g/day) diet, after a high-fat (150 g/day), normal oxalate diet and after and after a high-oxalate (500 mg/day) diet. Urinary oxalate concentrations were significantly (P less than 0.05) higher in patients with Crohn's disease and steatorrhoea, but not in those with chronic pancreatitis, after administrating a high-oxalate diet compared with healthy subjects. Mean oxalate values were 19.1 mg/24 h in controls compared with 65.8 mg/24 h in Crohn's disease patients. A direct correlation (r = 0.37, P less than 0.01) was established between faecal rats and urinary oxalate after oval oxalate load: this correlation (r = 0.43, P less than 0.01) is closer when only patients with Crohn's disease are considered. The study, therefore, confirmed a correlation between steatorrhoea and hyperoxaluria in patients with Crohn's disease; however, the high percentage of false positive results limits the use of urinary oxalate concentrations as a reliable indicator of lipid malabsorption. It is concluded that, at present, measurement of urinary oxalate cannot be recommended as a valid alternative to the Van de Kamer method for diagnosing lipid malabsorption.     

Different behaviour of the N-terminal and C-terminal fragment of proatrial natriuretic factor in plasma of healthy subjects as well as of patients with cirrhosis

N-terminal (atrial natriuretic factor (ANF) 1-98) and C-terminal (ANF 99-126) fragments of proatrial natriuretic factor (NTA and CTA, respectively) were determined in plasma of healthy subjects adopting different postures and in patients with cirrhosis. Seven healthy subjects were investigated while seated and 30 min after assuming a horizontal position. NTA plasma concentrations increased in subjects in the horizontal position (from 734 +/- 250 (SE) fmol/ml to 902 +/- 227 fmol/ml; p less than 0.05). In contrast, CTA plasma concentrations remained unchanged (9.2 +/- 1.3 fmol/ml vs 8.9 +/- 1.6 fmol/ml). In 10 patients with cirrhosis of the liver, NTA concentrations were markedly (p less than 0.001) elevated compared to 11 healthy subjects (2334 +/- 291 fmol/ml vs 743 +/- 155 fmol/ml). However, there was no difference of CTA plasma levels between cirrhotic patients and healthy subjects (8.7 +/- 1.3 fmol/ml vs 8.2 +/- 0.9 fmol/ml). These data demonstrate changes of the plasma concentration of the N-terminal fragment of proatrial natriuretic factor by posture and in liver disease, in contrast to unchanged levels of the C-terminal fragment.     

The renin-angiotensin-aldosterone system and arterial hypertension in patients with rheumatoid arthritis

Renin-angiotensin-aldosterone++ system was investigated in 60 patients suffering from rheumatoid arthritis. Forty-four of them (group 1) had arterial hypertension (144 +/- 4/94 +/- 2 mm Hg), sixteen were free of hypertension (120 +/- 3/80 +/- 1 mm Hg). Twenty-nine control subjects comparable by AH standing and demographic parameters had essential hypertension stage IB-IIA by A. L. Myasnikov classification (141 +/- 3/89 +/- 1 mm Hg). A tendency to renin suppression was dominating in 72% of group 1 patients (plasma renin activity less than 1.0 ng/ml/h). In this group there appeared high concentrations of A II (14.2 +/- 3.1 pg/ml) and plasma aldosterone++ (238 +/- 94 ng/ml). Rheumatoid vasculitis manifested in 86% of patients. Control subjects exhibited plasma renin activity greater than 3.0 ng/ml/hin 48%, average A II concentration was similar to that of group 1 (12.4 +/- 2.7 ng/ml/h, p greater than 0.05), plasma aldosterone++ level was significantly lower (176 +/- 29 ng/ml, p less than 0.05). Correlations were established between A II concentration and ESR (r = 0.39, p less than 0.05), A II and rheumatoid factor titers (r = 0.40, p less than 0.05). These indicate that immunopathological reactions are responsible for shifts in renin-angiotensin-aldosteron system in hypertensive rheumatoid arthritis subjects.     

Blood levels of angiogenin and vascular endothelial growth factor are elevated in myelodysplastic syndromes and in acute myeloid leukemia

Angiogenesis is of prognostic importance not only in solid tumors but also in malignant blood diseases. We measured levels of vascular endothelial growth factor (VEGF), angiogenin (ANG), and basic fibroblast growth factor (bFGF) in peripheral blood samples from 65 patients with myelodysplastic syndrome (MDS), from 25 patients with de novo acute myeloid leukemia (AML), and from 50 healthy donors. In matched samples, VEGF levels in serum were substantially higher than VEGF levels in plasma (380.7 +/- 56 pg/ml vs. 45.3 +/- 4.5 pg/ml, mean +/- SEM, p < 0.001), whereas serum and plasma levels of ANG were comparable and significantly correlated (r = 0.8; p < 0.01). Compared to normal controls (1.3 +/- 0.09 pg), serum levels of VEGF corrected for the peripheral blood platelet count (VEGF/10(6) platelets, VEGF(PLT)) were elevated in patients with refractory anemia (RA; 3.1 +/- 0.8 pg, p < 0.01), and reached maximal values in patients with advanced stage MDS (RAEB, RAEB-t) (3.5 +/- 0.6 pg, p < 0.001), de novo AML (3.6 +/- 1.1 pg, p < 0.05), and chronic myelomonocytic leukemia (CMML; 3.7 +/- 0.9 pg; p < 0.001). Levels of soluble ANG were elevated in RA (351 +/- 25.7 ng/ml, p < 0.001), in RAEB/RAEB-t (402 +/- 17.9 ng/ml; p < 0.001), in CMML (413.8 +/- 29.5 ng/ml; p < 0.001), and in patients with AML (305.1 +/- 17.1 ng/ml; p < 0.01, controls 255.4 +/- 8.1 ng/ml). Serum bFGF was neither elevated in MDS nor in AML patients. These results suggest that VEGF(PLT) is a marker of disease progression in MDS. Moreover, we show for the first time that elevated blood levels of ANG can be found in patients with myeloid malignancies, suggesting a role of ANG in the pathogenesis of these diseases.     

Heterogeneity of plasma glucagon. Circulating components in normal subjects and patients with chronic renal failure.

Plasma immunoreactive glucagon (IRG) concentrations were measured in 36 patients with chronic renal failure (CRF) and 32 normal subjects. In addition, the components of circulating IRG were analyzed by gel filtration in the fasting state and after physiological stimuli. Fasting IRG was elevated (P less than 0.001) in CRF patients (534 +/- 32 pg/ml) compared with the levels found in healthy subjects (113 +/- 9 pg/ml). Oral glucose suppressed plasma IRG in CRF patients from a basal level of 568 +/- 52 to a nadir of 354 +/- 57 pg/ml (120 min). This degree of suppression (38%) was comparable to that found in normal subjects (basal = 154 +/- 20 to 100 +/- 23 pg/ml) at 120 min (35%). Intravenous infusion of arginine (250 mg/kg) resulted in a 71% rise in IRG in CRF patients and a 166% increase in normal subjects. Gel filtration of fasting plasma from CRF patients showed three major peaks. The earliest (A) was found in the void volume (mol wt greater than 40,000) and constituted 16.5 +/- 4.7% of the elution profile. The middle peak (B) eluted just beyond the proinsulin marker (approximately 9,000 mol wt) and constituted the largest proportion of the elution profile (56.5 +/- 3.4%). The third peak (C) coincided with the standard glucagon and [125I]glucagon markers (3,485 mol wt) and comprised 27.0 +/- 4% of the IRG profile. In contrast, only peaks A and C were found in fasting plasma of normal subjects (53.6 +/- 10.4% in A and 46.4 +/- 10.4 in C). After oral glucose, glucagon immunoreactivity in the 3,500 mol wt peak (C) was markedly suppressed, while the B peak in patients with CRF declined to a lesser extent. The A peak in both groups was unchanged. After an arginine infusion only the C peak increased in both groups of subjects. Gel filtration of plasma in 3 M acetic acid gave similar profiles to those obtained in glycine albumin buffer. Exposure of serum to trypsin indicated that the B and C peaks were digestible, while the A peak was resistant to the action of the enzyme. In one sample, peak C increased after a 2-h exposure of serum to trypsin. We conclude that circulating IRG in normal subjects and patients with CRF is heterogenous. The hyperglucagonemia of renal failure is largely due to an increase in IRG material of approximately 9,000 mol wt, consistent with proglucagon, although the 3,500 mol wt component is also considerably elevated (threefold). The significance of circulating IRG levels should be interpreted with caution until the relative biological activity of the three components is established.     

Can plasma human pancreatic polypeptide be used to detect diseases of the exocrine pancreas?

Plasma concentrations of human pancreatic polypeptide (HPP) parallel exocrine pancreatic secretion in response to stimulation with cholecystokinin. We determined prospectively the relationships among fasting HPP level, integrated HPP response to infusion of cholecystokinin, and output of trypsin and also the sensitivity, specificity, and predictive values of the fasting HPP level in the diagnosis of exocrine pancreatic disease. Our study group consisted of 19 patients with acute pancreatitis, 17 with chronic pancreatitis, and 25 with ductal adenocarcinoma of the pancreas and 27 control subjects. In the control patients and those with chronic pancreatitis, significant correlations were detected between HPP level and output of trypsin (P less than 0.001) in response to infusion of cholecystokinin and between fasting HPP and integrated HPP levels (P less than 0.004); no correlation was detected between HPP level and steatorrhea. The sensitivity, specificity, and negative and positive predictive values of the fasting HPP level for detection of either chronic pancreatitis or pancreatic cancer were similar and approximated 0.88, 0.67, 0.88, and 0.66, respectively. The HPP concentration had no value in detecting acute pancreatitis. Because the fasting HPP level has a high degree of negative predictability and is simpler to measure than the integrated HPP level or the output of trypsin, it may be a useful test in patients suspected of having either chronic pancreatitis or pancreatic cancer. A fasting HPP level of 125 pg/ml or greater could be used to exclude chronic pancreatitis or pancreatic cancer, but the finding of a value of less than 125 pg/ml necessitates use of other diagnostic tests for reliable determination of the presence of these diseases.     

The dopaminergic regulation of plasma growth hormone secretion in normal subjects

The role of endogenous dopamine (DA) on plasma GH secretion was studied using domperidone (DA receptor blocker which does not cross blood brain barrier) in 16 normal subjects. After a bolus injection of domperidone (10 mg, i.v.), plasma PRL in 11 cases rose quickly and markedly from the basal level of 9.5 +/- 1.2 ng/ml (Mean +/- S.E.) to a maximum of 76.3 +/- 10.6 ng/ml at 30 min. In contrast, plasma GH in these cases showed a delayed and slight increases to domperidone injection where the values at 90 min and 120 min (3.5 +/- 0.8 ng/ml and 3.7 +/- 1.0 ng/ml) were significantly higher than those in control study (1.2 +/- 0.2 ng/ml and 1.0 +/- 0.1 ng/ml; p less than 0.05; n = 8). Domperidone infusion (0.22 mg/min/3 hr) was performed in the remaining 5 subjects. The plasma PRL responses were similar to those in the bolus injection of domperidone. These PRL responses were not modified when L-dopa was administered 30 min after the start of iv infusion of domperidone. Plasma GH showed slight but significant increases 135 min after the infusion compared to control study (4.3 +/- 1.2 ng/ml vs. 1.0 +/- 0.1 ng/ml; p less than 0.05). By the prior infusion of domperidone plasma GH responses to L-dopa was delayed and blunted, i.e., the occurrence of elevation and peak value of GH delayed by 15 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radioimmunoassay of glandular kallikrein in human plasma after partial purification by immunoaffinity column

Glandular kallikrein in human plasma was partially purified by immunoaffinity column (1.0 X 2.0 cm) and was measured by a radioimmunoassay (RIA). Plasma (5-10 ml) was diluted with an equal volume of 10 mmol/l sodium phosphate buffer, pH 7.4, containing 0.9% NaCl (PBS) and was applied to an immunoaffinity column from which glandular kallikrein was eluted with 3 mol/l NaSCN (20 ml). The enzymic fraction was concentrated with an Amicon PM 10 filter and dialyzed against PBS. The final recovery of the enzyme was 51.6 +/- 1.6% (mean +/- SD), determined by using [125I]kallikrein. The usable range of the standard curve covered 2.5-100 ng/tube. The coefficient of variation within the series was 5.9%, and the coefficient of variation between the series was 7.6%. In healthy controls (n = 25), the plasma content of glandular kallikrein was 1.36 +/- 0.39 ng/ml. In patients with acute pancreatitis (n = 6), the plasma concentration was 8.02 +/- 6.15 ng/ml, significantly different from the control group (p less than 0.01).     

Role of circulating somatostatin in regulation of gastric acid secretion, gastrin release, and islet cell function. Studies in healthy subjects and duodenal ulcer patients.

Studies were designed (a) to determine whether somatostatin is released into the circulation after meals in sufficient amounts to regulate gastric or pancreatic islet function in humans and (b) to investigate the possible role of somatostatin in the pathogenesis of duodenal ulcer disease. Mean plasma somatostatin-like immunoreactivity (SLI) increased from 6.2 +/- 1.5 pg/ml to a peak level of 13.8 +/- 1.3 pg/ml in eight healthy subjects after a 1,440-cal steak meal (P less than 0.005). When somatostatin-14 was infused intravenously, basal and food-stimulated gastric acid secretion and also basal and food-simulated plasma insulin and glucagon concentrations were reduced significantly at mean plasma SLI concentrations within the range seen after a meal. Thus, the amount of somatostatin reaching the systemic circulation after a steak meal was sufficient to inhibit gastric acid secretion and islet cell function. On the other hand, basal and food-stimulated plasma gastrin concentrations were reduced by intravenous somatostatin only at plasma SLI concentrations that were several-fold greater than post-prandial SLI concentrations. Although duodenal ulcer patients had significantly higher basal, food-stimulated, and peak pentagastrin-stimulated gastric acid secretion rates than healthy controls, duodenal ulcer patients and controls had nearly identical basal and food-stimulated SLI concentrations. Moreover, food-stimulated gastric acid secretion and gastrin release were inhibited by intravenous somatostatin to the same extent in ulcer patients and controls. These studies suggest that duodenal ulcer patients release normal amounts of somatostatin into the circulation and that target cells controlling acid secretion and gastrin release are normally sensitive to somatostatin in these patients.     

Plasma bradykinin levels in human chronic congestive heart failure

Induction of congestive heart failure by high-frequency pacing has been reported to increase plasma levels of immunoreactive kinins in dogs. In the present study, we evaluated plasma bradykinin levels in human heart failure. Utilizing a recently developed method, we specifically measured plasma levels of bradykinin-(1-9) nonapeptide in 21 patients with chronic congestive heart failure [New York Heart Association (NYHA) stages III and IV). At the same time, we measured plasma atrial natriuretic peptide levels and plasma renin activity, and, as a marker of inflammation, plasma levels of tumour necrosis factor. In addition, 18 healthy subjects matched for gender and age served as normal controls. Plasma bradykinin concentrations were not higher in patients with chronic congestive heart failure (median 2.1 fmol/ml) than in healthy subjects (2.6 fmol/ml). In contrast, plasma atrial natriuretic peptide levels were clearly higher (patients, 63 fmol/ml; controls, 24 fmol/ml; P<0.0001), despite diuretic treatment and in the presence of high plasma renin activity (patients, 13.0 ng x h(-1) x ml(-1); controls, 0.3 ng x h(-1) x ml(-1); P<0.0001). Tumour necrosis factor was elevated in heart failure patients in NYHA class IV only (27 pg/ml, compared with 21 pg/ml in controls; P=0.013). Bradykinin, atrial natriuretic peptide and plasma renin activity levels were not correlated with the severity of the disease, as assessed by NYHA classification. These results indicate that a rather selective cytokine activation, without concomitant stimulation of the kallikrein-kinin system, occurs in human chronic congestive heart failure.     

Plasma adiponectin and hyperglycaemia in diabetic patients.

The insulin-sensitising adipose hormone adiponectin is reduced in type 2 diabetic patients. We assessed the relationships between plasma adiponectin and chronic hyperglycaemia. Adiponectin levels and glycated haemoglobin (HbA1c) were measured at enrolment and after 90 days in 16 patients with type 2 diabetes aged (mean +/- SEM) 63.0 +/- 0.6 years, with body mass index (BMI) 30.2 +/- 0.5 kg/m2 and HbA1c concentration 7.4 +/- 0.1%, who did not modify their hypoglycaemic treatment during the observation period. Furthermore, plasma adiponectin was measured in 29 adult patients with type 1 diabetes and compared with 29 control subjects matched for sex, age, BMI, waist circumference and bioimpedance-estimated fat mass. In type 2 diabetic patients at enrolment, adiponectin concentration correlated with BMI (r = -0.46; p < 0.05), but not with HbA1c. During the prospective observation, variations of adiponectin showed a significant correlation with variations of BMI (r = -0.47; p < 0.01), but not with variations of HbA1c concentration. These results were confirmed by multivariate analysis after adjustment for sex and age. Adiponectin levels in type 1 diabetic patients (380.8 +/- 13.7 ng/ml in women, 192.5 +/- 13.9 ng/ml in men) were significantly (p < 0.05) higher than in control subjects (277.6 +/- 11.0 ng/ml in women, 102.7 +/- 5.1 ng/ml in men); plasma adiponectin correlated significantly with BMI and waist circumference, but not with HbA1c. In conclusion, the reduction of plasma adiponectin levels in type 2 diabetic patients does not appear to be determined by chronic hyperglycaemia. Adiponectin levels are increased in type 1 diabetes, but this phenomenon is not attributable to differences in nutritional status or body composition.     

Correlation of MRCP quantification (MRCPQ) with conventional non-invasive pancreatic exocrine function tests

PURPOSE: To correlate MRCP quantification (MRCPQ) of pancreatic fluid output following secretin with steatorrhoea, urinary pancreo-lauryl (PL) or fecal elastase 1 (FE1) tests. METHODS AND MATERIALS: Sixty-one patients, 36 male, median age 51 years (23-78) with known or suspected pancreatic disease who had undergone both MRCPQ and FE1 or PL were included. Twenty-nine patients had chronic pancreatitis, five acute pancreatitis, seven normal, five pancreas divisum, four pancreatic atrophy, three pancreatic duct obstruction, two post-surgical and six miscellaneous diagnoses. Clinical assessment of steatorrhoea was available in 29. MRCP was performed before and at 2 min intervals after 0.1 ml/kg IV Secretin. Changes in signal intensity in the imaging volume were plotted against time and the flow rate derived from the gradient. Scatter plots, Pearson correlation coefficient, and the Fisher Exact test were performed. RESULTS: MRCPQ was significantly different (p = 0.012) between those with/without steatorrhoea; mean +/- SD (95% CI) were 4.0 +/- 1.5 (3.1:4.9, n = 16) and 6.3 +/- 2.9 (4.7:7.8, n = 13). Fifty-one paired FE1-MRCPQ and 24 PL-MRCPQ data sets were analysed. Both the Pearson correlation coefficient (FE1 p = 0.001 and %TK p = 0.003) and the Fisher Exact test were significant (FE1 p = 0.016 and %T/K 0.03). CONCLUSIONS: MRCPQ correlated with steatorrhoea, PL and FE1.     

A cytokine status in chronic alcoholic and biliary pancreatitis

AIM: To determine characteristics of a cytokine status in chronic pancreatitis (CP) depending on etiological factor, stage of the disease, complications, therapy. Material and methods. 72 patients had chronic alcoholic pancreatitis (CAP), 38 patients--chronic biliary pancreatitis (CBP). Control group consisted of 20 healthy subjects. RESULTS: At early stages and height of CAP exacerbation, concentrations of IL-1beta, IL-6, IL-8, TNF-gamma and TNFalpha were elevated (951.1 +/- 104.2 pg/ml; 172.8 +/- 24.3 pg/ml; 432.6 +/- 68.5 pg/ml; 823.3 +/- 97.5 pg/ml; 158.7 +/- 19.6 pg/ml, respectively). Regenerative processes in CP were accompanied with IL-4 elevation to 614.9 +/- 64.6 pg/ml. In CAP without complications and with them the levels of cytokines differed significantly. The level of TGF-beta1 stimulating development of fibrosis was in CAP patients 627.8 +/- 92.2 pg/ml, in CAP patients with complications--796.8 +/- 102.5, in the controls--40.2 +/- 4.6 pg/ml (p < 0.05). In early stages of CBP exacerbation, IL-1beta rose to 527.2 +/- 62.7 pg/ml, IL-6--to 80.9 +/- 11.4 pg/ml, IL-8--to 290.4 +/- 46.8 pg/ml, INF-gamma to 853.3 +/- 91.6 pg/ml; TNF-alpha--to 79.7 +/- 8.3 pg/ml, TGF-beta1--534.1 +/- 78.4 pg/ml. With attenuation of acute syndromes and development ofregeneration, levels of IL-4 went up (226.7 +/- 32.4 pg/ml). CONCLUSION: CP is accompanied by increase in cytokine contents depending on the etiological factor, variants of course, stage, presence of complications.     

Plasma leptin levels in rats with pancreatitis

Diagnosis of pancreatitis is based on the determination of serum amylase and lipase levels. However, recent identification of specific leptin receptors in the pancreas suggests that this peptide may also play some roles in the modulation of pancreatic function. The objective of the present study was to investigate the relationship between serum leptin levels and pancreatitis. Thirty male Wistar rats were divided into 3 groups: the control group, acute pancreatitis group and chronic pancreatitis group. Pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. A sham laparotomy was performed in the control group. Control and acute pancreatitis groups were sacrificed 24 hours later, and chronic pancreatitis group was sacrificed on postoperative day 7. Blood was taken by cardiac puncture for the determination of plasma leptin levels, and the pancreatic tissue was excised for histopathologic confirmation of pancreatitis. Plasma leptin rose significantly from the median of 0.78 +/- 0.12 ng/ml in the control group to 1.92 +/- 0.10 ng/ml and 1.86 +/- 0.13 ng/ml in acute and chronic pancreatitis groups, respectively (p < 0.001, for both). There was no significant difference in the plasma leptin levels between the acute pancreatitis group and the chronic pancreatitis group (p > 0.05). These findings confirm that leptin has a role in pancreas inflammation, and the inflamed tissue can be the source of local production of leptin.