Plasma trypsin in chronic pancreatitis and pancreatic adenocarcinoma.

We have used a simple and precise radioimmunoassay to measure trypsin in human plasma. Fasting plasma trypsin concentrations were extremely low in patients with chronic pancreatitis with steatorrhoea (5 +/- 2 ng/ml) when compared to healthy controls (86 +/- 7 ng/ml, p less than 0.001). In patients with chronic pancreatitis but no steatorrhoea basal plasma trypsin levels were similar to those of the normal controls (99 +/- 25 ng/ml). A small but significant postprandial rise in plasma trypsin concentrations was observed in normal subjects (mean increment 15 +/- 4%, p less than 0.005, paired t test) but was absent in patients with chronic pancreatitis with steatorrhoea. In contrast to exocrine deficient chronic pancreatitis, other malabsorptive conditions associated with steatorrhoea (active coeliac disease and acute tropical sprue) demonstrated mean fasting trypsin concentrations similar to controls. Patients with adenocarcinoma of the pancreas had basal trypsin concentrations similar to healthy subjects as did patients with adenocarcinoma of the stomach, colon, rectum, brochus, and breast. In some cases measurement of plasma trypsin may be of help in the differential diagnosis of steatorrhoea.     

Plasma α2-macroglobulin-trypsin complexlike substance (MTLS) in pancreatic disease

α2-macroglobulin-trypsin complexlike substance (MTLS) was determined in plasma of pancreatic and nonpancreatic diseases using a two-step enzyme immunoassay to study the diagnostic and pathophysiological significance of MTLS. Plasma levels of MTLS in acute pancreatitis (mean ± SD = 265.6 ± 346.2 ng/ml, n = 9), calcified chronic pancreatitis (128.6 ± 257.4, n = 13), and noncalcified chronic pancreatitis (13.5 ± 12.5, n = 10) were significantly higher than that in controls (3.6 ± 1.8, n = 81). In other diseases such as gastric cancer, hepatoma, diabetes mellitus, and gallstones, MTLS values were not different from those of control. Plasma MTLS values showed low correlation with serum trypsin, elastase 1, pancreatic amylase, lipase, and pancreatic secretory trypsin inhibitor (PSTI). The elevation of plasma MTLS values in acute pancreatitis suggests that plasma MTLS levels reflect that protease is inappropriately activated in pancreatic acinar cell and released into the circulation and that the determination of MTLS can be useful for diagnosis and pathophysiology of acute pancreatitis and chronic pancreatitis. © 1996 Wiley-Liss, Inc.     

Serum pancreatic secretory trypsin inhibitor in pancreatic disease

The clinical usefulness of serum pancreatic secretory trypsin inhibitor (PSTI) in pancreatic diseases was evaluated. The mean serum PSTI level of 41 healthy normal persons was 9.4 ng/ml (ranging from 5.2 to 16.7 ng/ml). Serum PSTI levels were abnormally raised in all patients with acute pancreatitis ranging from 35.0 to 4500 ng/ml, but were almost within normal range in patients with chronic pancreatitis, pancreatic cyst, acute abdominal emergencies such as perforated ulcer and intestinal obstruction, and macroamylasemia. There was no correlation between serum PSTI levels and total or pancreatic-type isoamylase activity. Patients with acute pancreatitis in whom the elevation of serum PSTI was transient and occurred after that of serum amylase activity had relatively mild symptoms and recovered along with normalization of serum PSTI levels. On the other hand, patients whose serum PSTI values became increased coincidentally with serum amylase activity and remained elevated, had severe clinical symptoms and unfavorable clinical outcome. Of 2 patients who underwent partial pancreatectomy, the serum PSTI level increased markedly in one who developed postoperative pancreatitis but not in the other without pancreatitis. In contrast to patients with acute pancreatitis, the serum response to the secretin stimulation in patients with chronic pancreatitis, was only small and transient, reaching the maximum at 10 min after administration of secretin. These results suggest that measurement of serum PSTI concentration may be useful in the diagnosis of acute pancreatitis and that the degree of rise and the duration of the elevated levels of serum PSTI are closely related to the severity of acute pancreatitis.     

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.     

Sonographic evaluation of the pancreatic duct in normal children and children with pancreatitis.

We investigated the diameter of pancreatic duct using ultrasonography in 51 children with pancreatitis and age-matched healthy control children over a 5 year period. The diameters of pancreatic duct and pancreatic body were measured simultaneously by sonography. The mean ages of children with acute pancreatitis and chronic pancreatitis were 9.7 +/- 3.9 and 10.3 +/- 3.1 years, respectively (range, 1 to 8 years). The mean age of normal children was 9.6 +/- 5.3 years. A significant difference was found in diameter of the pancreatic duct between children with acute and chronic pancreatitis versus that of age-matched control. In addition, a significant difference in diameter of the pancreatic body was found between children with acute pancreatitis and age-matched controls, but there was no marked difference in diameter of the pancreatic body between normal persons and those with chronic pancreatitis. The mean diameters of the pancreatic duct in acute pancreatitis and chronic pancreatitis were 2.34 +/- 0.47 mm and 2.84 +/- 0.67 mm, respectively, which was greater than that of normal children (1.65 +/- 0.45 mm). Pancreatic ducts with diameters greater than 1.5 mm in children between 1 and 6 years, greater than 1.9 mm at ages 7 to 12 years, or greater than 2.2 mm at ages 13 to 18 years were significantly associated with the presence of acute pancreatitis. Thirty-two patients, including 25 with acute pancreatitis and 7 with chronic pancreatitis, underwent follow-up measurement of pancreatic duct and serum lipase examination on at least three occasions. A good correlation between the diameter of pancreatic duct and serum lipase level was found. Thus, ultrasonography of the pancreatic duct is valuable in diagnosis and monitoring of pancreatitis in children.     

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.     

Origin of serum catalase activity in acute pancreatitis

Serum catalase activity was examined in 96 patients with the oedematous form and in 15 patients with the necrotic form of acute pancreatitis. Total catalase release into plasma was estimated to be 2,140 +/- 947 kU and 4,764 +/- 1,505 kU, respectively. The g equivalents of pancreas were 163 +/- 72 g and 362 +/- 133 g, being 2.03-fold and 4.52-fold higher than the whole mass of pancreas indicating the nonpancreatic origin of the total increase of serum catalase. In both types of acute pancreatitis serum haemoglobin, haematin, haptoglobin and LDH values supported the presence of haemolysis. The volumes of blood were 22.6 +/- 10.1 ml and 50.4 +/- 15.9 ml which are only 0.41% and 0.91% of the total blood volume. Taking these findings into account, in acute pancreatitis the major part of increase of serum catalase can be explained by its release from the erythrocytes.     

矽肺患者血清瘦素及增食欲素水平变化分析

【目的】探讨矽肺患者瘦素、增食欲素浓度水平变化。【方法】选取矽肺患者32例（矽肺组）,慢性阻塞性肺疾病（COPD）患者33例（COPD组）和健康体检者30例（对照组）。EDTA抗凝管采集三组患者空腹静脉血4mL,检测并比较三组血浆瘦素、增食欲素浓度。【结果】矽肺组瘦素及增食欲素浓度分别为（485．13±286．42）ng／mL、（151．14±129．57）ng／mL,与COPD组瘦素浓度（457．22±235．98）ng／mL和增食欲素浓度（132．81±101．26）ng／mL比较升高,但差异无显著性（P〉0．05）;与对照组瘦素浓度（316．26士169．15）ng／mL和增食欲素浓度（89．57±83．64）ng／mL比较显著升高,差异有显著性（P〈0．05）。【结论】矽肺患者血浆瘦素、增食欲素浓度均明显升高,推断血浆瘦素、增食欲素浓度变化可能与营养不良相关。     

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.     

Rosiglitazone promotes pancreatic regeneration in experimental model of acute pancreatitis

Acute pancreatitis is an inflammatory disease of the pancreas caused by release of activated digestive enzymes in the pancreas. A number of therapeutic options have been explored for acute pancreatitis, but none has been unambiguously proven to be effective. Rosiglitazone has been shown to be efficacious in acute pancreatitis; thus, the present study was planned to evaluate the effect of rosiglitazone on pancreatic regeneration. Pancreatitis was induced by l ‐arginine in rats which were divided into three groups: cholecystokinin (CCK‐8), rosiglitazone and vehicle. Rats were sacrificed at four time points after induction of pancreatitis i.e. 24 h, day 3, day 14 and day 28 for determination of biochemical parameters and histological examination. Rate of DNA synthesis, immunohistochemistry and RT‐PCR were performed at day 3 and day 7. Drug administration was started 2 h after last L ‐arginine injection and continued till the day of sacrifice. The lower levels of enzyme in rosiglitazone‐treated group compared to vehicle group proved the efficacy of rosiglitazone treatment in reducing severity of acute pancreatitis. The nucleic acid content and rate of DNA synthesis were significantly higher in rosiglitazone group indicating promotion of pancreatic regeneration. The histopathological score were lower in rosiglitazone group. Rosiglitazone treatment promoted pancreatic regeneration after acute injury. Currently, only symptomatic treatment is available, regeneration of pancreatic tissue can be a future strategy in the management of acute pancreatitis. Further studies are required to support the findings of the present study.     

Prevalence, causes and effects of increased iron storage in patients with kidney transplantation

Patients on chronic hemodialysis often need blood transfusions due to erythropoietin deficiency. Even after successful kidney transplantation iron overload may persist. Former histological studies have revealed siderosis of the liver in 69% of all patients whose serum ferritin was above 1100 ng/ml. The aim of the present study was to evaluate the influence of iron overload on liver function. In 146 symptom free patients with renal allografts serum ferritin was determined to detect possible iron overload. Serum ferritin between 4 and 5480 ng/ml were found (women: 358.7 +/- 105.3; men 282.4 +/- 63.3 ng/ml; x +/- SEM). Twelve patients (8.1%) had ferritin levels higher than 1100 ng/ml. These twelve patients as well as another group of eight patients with renal allografts whose serum ferritin was known to be higher than 1100 ng/ml were included for further evaluation. Their data were matched and compared with those of a control group also patients with renal allograft (same age and sex) whose serum ferritin was lower than 1100 ng/ml. Transaminases (SGPT 22.6 +/- 3.6 vs. 15.4 +/- 6.0 U/l; SGOT 14.7 +/- 2.0 vs. 13.0 +/- 4.8 U/l) and plasma glucose (90.5 +/- 7.1 vs. 76.8 +/- 3.7 mg/dl) were found to be significantly higher (p less than 0.05) in patients with serum ferritin levels above 1100 ng/ml. Elevated transaminases were significantly more frequent in patients with high serum ferritin (9 vs. 2; p less than 0.02) as compared with the control. Ferritin levels significantly correlated with the number of preceding blood transfusions (p less than 0.002). Hbs-persistence was detected in six out of 20 patients with high ferritin levels but only in one out of 20 in the control group (p less than 0.05) whereas anti-Hbs prevalence was not different in the two groups. These data indicate that chronic iron overload should be considered as a possible cause of chronic liver disease in patients with renal allografts.     

Serum human pancreatic elastase I levels in pancreatic disease

The serum elastase concentration has been measured in 25 healthy individuals, sixteen patients with tumours involving the pancreas, nine patients with acute pancreatitis and nine patients with chronic pancreatitis. The elastase concentrations were increased in those with pancreatic tumours particularly when the head of the pancreas was involved. In acute pancreatitis, the serum elastase showed a proportionally greater increase than did the serum amylase and maintained abnormal levels for a longer period. In six out of nine patients with chronic pancreatitis the serum elastase level was within the reference range for healthy individuals.     

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.     

大黄素对急性坏死性胰腺炎的防治作用

目的研究大黄素对急性坏死性胰腺炎(Acute necrotizing pancreatitis,ANP)大鼠是否有保护作用。方法 40只健康雄性SD大鼠随机分为4组,对照组、ANP组、大黄素预防组,大黄素治疗组。大剂量精氨酸腹腔注射诱导ANP模型,预防组于造模前90min给予大黄素25mg/kg,两次,每次间隔1h,治疗组于造模后30min给予大黄素25mg/kg,两次,每次间隔1h。各组大鼠于造模后24h处死,观察大鼠血浆肾素、血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)、AMY、TNF-α、IL-1β水平变化,并检测胰腺/体重比值、胰腺病理变化。结果 ANP组肾素、AngⅡ、AMY、TNF-α、IL-1β、胰腺/体重比值均较对照组明显升高;胰腺组织广泛坏死,弥漫性水肿及大量炎细胞浸润,胰腺小叶结构破坏严重。大黄素预防组和治疗组血浆AMY、TNF-α、IL-1β、胰腺/体重比值较ANP组明显下降,胰腺组织病理损伤明显减轻,而血浆肾素、AngⅡ水平较ANP组变化不明显。结论大黄素对血浆肾素、AngⅡ水平无明显影响,但可减少AMY、TNF-α、IL-1β的产生,减轻胰腺组织的病理损伤,对ANP损伤具有保护作用。     

急性胰腺炎血中抗炎性细胞因子的变化和生长抑素的调节作用

目的探讨急性胰腺炎时血中抗炎性细胞因子白介素10(IL10)和转化细胞生长因子β(TGFβ)的变化、意义及生长抑素的调节作用。方法实验用SD大鼠,分为正常对照组、胰腺炎组〔采用开腹胰管注射5%牛磺胆酸钠(1.0ml/kg)诱导急性胰腺炎,不治疗〕和生长抑素治疗组(胰腺炎诱导成功后0.5小时静注施他宁20μg/kg)。后2组动物在术后2、6和24小时处死,抽血用酶联免疫吸附(ELISA)法检测血中IL10、TGFβ、胰淀粉酶含量及胰腺湿重。结果正常对照组动物血IL10为(32.05±14.87)ng/L,TGFβ为(66.40±13.20)ng/L。胰腺炎后24小时血IL10和TGFβ均显著升高,分别为(68.13±19.90)ng/L和(103.77±28.95)ng/L(P均<0.05);生长抑素治疗后24小时血IL10和TGFβ分别为(42.20±14.55)ng/L和(45.98±18.10)ng/L,两者均明显下降(P均<0.05)。结论急性胰腺炎时血中抗炎性细胞因子升高,并可能和胰腺炎后期的免疫抑制效应有关;生长抑素对抗炎性细胞因子的升高有抑制作用。     

Fluconazole penetration into the pancreas

Because of antibiotic prophylaxis for necrotizing pancreatitis, the frequency of fungal superinfection in patients with pancreatic necrosis is increasing. In this study we analyzed the penetration of fluconazole into the human pancreas and in experimental acute pancreatitis. In human pancreatic tissues, the mean fluconazole concentration was 8.19 +/- 3.38 microg/g (96% of the corresponding concentration in serum). In experimental edematous and necrotizing pancreatitis, 88 and 91% of the serum fluconazole concentration was found in the pancreas. These data show that fluconazole penetration into the pancreas is sufficient to prevent and/or treat fungal contamination in patients with pancreatic necrosis.     

厄贝沙坦对大鼠急性胰腺炎局部微循环改变的实验研究

目的 探讨血管紧张素受体拮抗剂对大鼠急性胰腺炎（AP）的保护作用.方法 40只Wistar 大鼠随机分为对照组和AP组,AP组分为模型组和高中低剂量组.测定血浆血管紧张素Ⅱ（AngⅡ）、淀粉酶（AMY）水平,观察胰腺组织病理学改变;采用异硫氰酸荧光素标记红细胞（FITC-RBC）技术及微循环观测系统观察大鼠胰腺微循环血液流速.结果 随着病变的进展,AP组胰腺炎病理由水肿向出血坏死发展,AngⅡ、AMY同步上升,胰腺局部组织血液流速降低.中剂量厄贝沙坦干预组则胰腺炎病理改变减轻,胰腺局部组织血液流速改善,且血浆AngⅡ、AMY水平低于模型组,其他剂量组之间各指标差异无统计学意义.结论血管紧张素受体拮抗剂对AP时胰腺微循环有明显的改善作用.     

Circulating leptin and body composition in chronic obstructive pulmonary disease

Nutritional depletion and weight loss are two features of chronic obstructive pulmonary disease (COPD), and the association between low body mass index (BMI) and poor prognosis in patients with COPD is a common clinical observation. Mechanisms of weight loss are still unclear in COPD. Excessive energy expenditure partly due to increased work of breathing was shown, but other mechanisms have been searched for. Leptin is a hormone secreted by adipocytes that plays an important role in energy homeostasis and regulates body weight through control of appetite and energy expenditure. The aim of this study was to evaluate the association of circulating leptin levels and measures of body composition in COPD patients. Thirty male COPD outpatients (mean age 66.3 +/- 8.4) and 20 controls (mean age 65.9 +/- 10.8) were included in the study. After standard spirometry and body composition measurements, serum leptin concentration was measured by ELISA assay. COPD patients were grouped according to BMI. Mean BMI was 19.01 +/- 2.26 kg/m2 in group 1 (COPD patients with low BMI), 26.85 +/- 4.51 in group 2 COPD (COPD patients with normal/high BMI) and 27.64 +/- 2.75 kg/m2 in healthy controls (group 3). Mean serum leptin concentration was 1.41 +/- 1.86 ng/ml in group 1, 2.60 +/- 1.38 ng/ml in group 2 and 2.82 +/- 1.46 ng/ml in group 3 (p = 0.002). Leptin correlated to not only BMI but also body weight, waist circumference, triceps and biceps skinfold thickness and body fat percent (p < 0.05 for all). Results of this study suggest that the cause of weight loss is not increased circulating leptin in COPD. Instead, leptin remains regulated in COPD and further decreased in patients with low BMI, probably as a compensatory mechanism to preserve body fat content, which should be evaluated in further studies.     

Increased serum levels of leptin in retinal vein occlusion

Retinal vein occlusion is an important cause of visual loss. Several ocular and systemic conditions have been reported for retinal vein occlusion. The pathogenesis of thrombus formation in the retinal vein, which results in retinal vein occlusion, is unclear. The aim of this study was to investigate the correlation between increased serum leptin levels and the occurrence of retinal vein occlusion (RVO). The study group consisted of 40 patients with RVO (58.1 +/- 6 years old; 17 males and 23 females): 15 patients with central RVO, 23 with branch RVO, and 2 with hemispheric RVO. The patients who had any ocular or systemic pathology were not included in the study. The control group consisted of 40 healthy individuals of similar gender, age, date and type of health survey, and geographic region. The blood samples of the RVO patients (n = 40) and controls (n = 40) were obtained antecubitally. Leptin levels were measured by an enzyme-linked immunosorbent assay (ELISA) method, and Student's t-test was used to determine differences between the groups. The mean serum leptin levels were 12.5 +/- 1.64 ng/ml in patients with RVO and 8.4 +/- 1.22 ng/ml in the control subjects; namely, the mean serum leptin levels were significantly higher in the patients with RVO (p < 0.001). These results suggest that leptin may be involved in the pathogenesis of venous thrombosis in the retina probably through its effects on homeostasis of the vessel wall.     

Immunoreactive tissue kallikrein in human serum

Human urinary kallikrein and an antiserum to it raised in the rabbit were used to detect and quantitate immunoreactive tissue kallikrein in human serum. Both 125I-labeled kallikrein and the unlabeled purified enzyme appear complexed to higher molecular weight entities in serum, but specific binding between radiolabeled enzyme and antiserum was unaffected by the presence of serum or plasma. Parallelism to standard displacement curves was always seen with radioimmunoassay of normal sera as well as with human mixed saliva or pancreatic extracts. Assay sensitivity is 160 pg/ml of serum, or 16 pg per tube. Purified plasma kallikrein or prekallikrein in concentrations up to 10 micrograms/ml showed no displacement. Acetone-kaolin activation of plasma produced the expected 30-fold increase in Tos-Arg-OMe esterase activity but no change in immunoreactive tissue kallikrein levels. Serum concentrations were 3.8 +/- 0.7 (mean +/- SE) ng/ml in 21 normal volunteers, and were similar in patients with Fletcher trait or Hageman factor deficiency. Significantly increased serum concentrations were seen with long-term low dietary sodium intake or acute forms of pancreatitis. Although the relation of this immunoreactive material to any active tissue kallikrein within the circulation remains to be determined, our studies provide a new parameter for the assessment of a system repeatedly suggested to have some role in regulation of vascular resistance.