Elastase Concentrations Research Articles

Risk factors of exocrine and endocrine pancreatic insufficiency after pancreatic resection: A multi-center prospective study

Between January 1, 2014 and June 19, 2015, 91 consecutive patients undergoing pancreatoduodenectomy (PD) or left pancreatectomy (LP) (72% and 28%, respectively) were followed prospectively. ExoPI was defined as fecal elastase content<200μg per gram of feces while EndoPI was defined as fasting glucose>126mg/dL or aggravation of preexisting diabetes. The volume of residual pancreas was measured according to the same principles as liver volumetry. The ExoPI and EndoPI rates at 6 months were 75.9% and 30.8%, respectively. The rate of ExoPI after PD was statistically significantly higher than after LP (98% vs. 21%; P<0.001), while the rate of EndoPI was lower after PD vs. LP, but this difference did not reach statistical significance (28% vs. 38.5%; P=0.412). There was no statistically significant difference in ExoPI found between pancreatico-gastrostomy (PG) and pancreatico-jejunostomy (PJ) (100% vs. 98%; P=1.000). Remnant pancreatic volume less than 39.5% was predictive of ExoPI. ExoPI occurs quasi-systematically after PD irrespective of the reconstruction scheme. The rate of EndoPI did not differ between PD and LP.

Plasma concentration of selected biochemical markers of endothelial dysfunction in women with various severity of chronic venous insufficiency (CVI)-A pilot study.

BackgroundAlthough the endothelial dysfunction is considered to be implicated in the pathogenesis of chronic venous insufficiency (CVI) the endothelial status in patients with venous disorders is still not fully evaluated. Therefore the aim of the study was to measure the concentration of selected markers of endothelial dysfunction: von Willebrand factor (vWf), soluble P-selectin (sP-selectin), soluble thrombomodulin (sTM) and soluble VE-cadherin (sVE-cadherin) in CVI women who constitute the most numerous group of patients suffering from venous disease.Materials and methodsForty four women with CVI were involved in the study and divided into subgroups based on CEAP classification. Concentration of vWf, sP-selectin, sTM and sVE-cadherin were measured and compared with those obtained in 25 healthy age and sex-matched women.ResultsIt was found that the concentration of sTM increased and sVEcadherin decreased along with disease severity in CVI women. A significant rise of sTM was observed especially in CVI women, with the highest inflammation status reflected by hsCRP or elastase concentration, and in CVI women with a high oxidative stress manifested by an increased plasma MDA. A significant fall of circulating sVE-cadherin was reported in CVI women with moderate to highest intensity of inflammation and oxidative stress. There was no change in vWF and sP-selectin concentration at any stage of CVI severity.ConclusionsThe results of the present study demonstrate the presence of endothelial dysfunction in women suffering from CVI which seems to progress with the disease severity and may be associated with inflammation and enhanced oxidative stress.

Laparoscopic Nissen fundoplication: The effects of high-concentration supplemental perioperative oxygen on the inflammatory and immune response: A randomised controlled trial.

Background:A number of studies have been reported on the effects of high-concentration oxygen (HCO) on cytokine synthesis, with controversial results. We assessed the effect of administration of perioperative HCO on systemic inflammatory and immune response in patients undergoing laparoscopic Nissen fundoplication (LNF).Materials and Methods:Patients (n = 117) were assigned randomly to an oxygen/air mixture with a fraction of inspired oxygen (FiO2) of 30% (n = 58) or 80% (n = 59). Administration was commenced after induction of anaesthesia and maintained for 6 h after surgery. White blood cells, peripheral lymphocytes subpopulation, human leucocyte antigen-DR (HLA-DR), neutrophil elastase, interleukin (IL)-1 and IL-6 and C-reactive protein (CRP) were investigated.Results:A significantly higher concentration of neutrophil elastase, IL-1, IL-6 and CRP was detected post-operatively in the 30% FiO2group patients in comparison with the 80% FiO2group (P < 0.05). A statistically significant change in HLA-DR expression was recorded post-operatively at 24 h, as a reduction of this antigen expressed on monocyte surface in patients from 30% FiO2group; no changes were noted in 80% FiO2group (P < 0.05).Conclusions:This study demonstrated that perioperative HCO (80%), during LNF, can lead to a reduction in post-operative inflammatory response, and possibly, avoid post-operative immunosuppression.

Exocrine pancreas function decreases during the progression of the beta-cell damaging process in young prediabetic children.

The function of the exocrine pancreas is decreased in patients with type 1 diabetes but it is not known when this defect develops. The current study set out to determine whether the reduced exocrine function becomes manifest after the initiation of islet autoimmunity. The study was nested in the prospective Type 1 Diabetes Prediction and Prevention study where children with human leukocyte antigen (HLA)-conferred susceptibility are observed from birth. Elastase-1 levels were analyzed from stool samples collected at the time of seroconversion to islet autoantibody positivity and at diagnosis of type 1 diabetes, as well as from samples taken from matched control children of similar age. Elastase levels were lower in case children at the time of the diagnosis of diabetes when compared to the control children. However, elastase concentrations did not differ between cases and controls at the time when autoantibodies appeared. The results suggest that the defect in the exocrine function develops after the appearance of islet autoantibodies. Further studies are needed to assess whether reduced elastase levels predict rapid progression of islet autoimmunity to clinical disease.

Undiagnosed pancreatic exocrine insufficiency and chronic pancreatitis in functional GI disorder patients with diarrhea or abdominal pain.

A previous UK study showed that 6.1% of patients with diarrhea-predominant irritable bowel syndrome (IBS-D) had evidence of severe pancreatic exocrine insufficiency (PEI), but these findings need replication. We aimed to identify the prevalence of PEI based on fecal elastase stool testing in consecutive outpatients presenting with chronic unexplained abdominal pain and/or diarrhea and/or IBS-D. Patients aged over 40years presenting to hospital outpatient clinics from six sites within Australia with unexplained abdominal pain and/or diarrhea for at least 3months and/or IBS-D were studied. Patients completed validated questionnaires and donated a stool sample in which elastase concentration was measured by ELISA. A concentration of <100mcg/g stool represented severe and <200mcg/g mild to moderate PEI. Patients whose fecal elastase was <200mcg/g underwent testing for pancreatic pathology with an endoscopic ultrasound or abdominal CT. Two hundred eighteen patients (mean age of 60years, 29.4% male) were studied. PEI was found in 4.6% (95% CI 2.2-8.3%) (n=10), with five patients (2.3% (95% CI 0.8-5.3%) having severe PEI. Only male sex and heavy alcohol use were significantly associated with abnormal versus normal pancreatic functioning. Of seven patients who underwent endoscopic ultrasound or CT, two had features indicative of chronic pancreatitis. One in 50 patients with IBS-D or otherwise unexplained abdominal pain or diarrhea have an abnormal fecal elastase, but unexpected pancreatic insufficiency was detected in only a minority of these. This study failed to confirm the high prevalence of PEI among patients with unexplained GI symptoms previously reported.

Development of fusiform aneurysms induced by topical application of elastase in a rabbit model

BackgroundResearch on the etiology and pathophysiology of fusiform aneurysm has been impeded due to the inability to collect fusiform aneurysm specimens. We aim to resolve this through the development of a novel fusiform aneurysm model in rabbits.MethodsSixty New Zealand White rabbits were divided into ten groups (n = 6 per group): groups A, B, C, D, E and groups a, b, c, d, e. Elastase, at a concentration of 0, 0.5, 1, 2.5 and 5 U/μL respectively was administered to each rabbit to incubate their carotid arteries. Three weeks later, angiography, histomorphometry, immunohistochemistry and immunofluorescent were performed.ResultsHeparin administration is indispensable. No thrombosis was observed in groups A, B, C, D and E, whereas, increased thromboembolism occurred in groups a, b, c, d and e. Based on the size and wall thickness of aneurysms specimens, 5 U/μL was the optimal concentration of elastase to induce fusiform aneurysms. At 5 U/μL, the intraluminal carotid diameter increased significantly from 2.50 ± 0.32 mm to 3.11 ± 0.55 mm (p < 0.01). The wall thickness significantly reduced from 176.0 ± 39.8 μm to 39.7 ± 14.6 μm (p < 0.01) post aneurysm induction. The histolopathological evaluation revealed the elastic lamina and the smooth muscle cell’s lamina were markedly attenuated and the intimal endothelial lamina became thin or even absent.ConclusionsOur research demonstrates that intracranial fusiform aneurysm could be modeled in rabbit carotid artery adventitia incubation by porcine pancreatic elastase.

Effect of processing banked suspended red blood cells with cell saver before priming on perioperative systemic inflammatory responses of infants undergoing cardiac surgery under cardiopulmonary bypass

Objective To evaluate the effects of processing banked suspended red blood cells (RBCs) with cell saver before priming on perioperative systemic inflammatory responses of infants undergoing cardiac surgery under cardiopulmonary bypass (CPB). Methods Forty pediatric patients of both sexes, aged 3 months-2 yr, weighing 5-13 kg, of American Society of Anesthesiologists physical status Ⅱ-Ⅳ, undergoing repair of atrial or ventricular septal defect under CPB, were divided into control group (group C, n=20) and processing group (group P, n=20) using a random number table.Banked suspended RBCs were primed directly after being added to CPB circuit in group C. Banked suspended RBCs were washed with cell saver and then primed after being added to CPB circuit in group P. At 5 min before skin incision, at 30 min after the start of CPB, at 10 min after aortic unclamping, immediately after the end of CPB and at 6, 12 and 24 h after the end of CPB (T1-7), blood samples were collected from the radial artery for determination of the concentrations of tumor necrosis factor, interleukin-1β (IL-1β), IL-6, IL-8, IL-10 and neutrophil elastase in plasma by enzyme-linked immunosorbent assay.Blood samples were taken from the radial artery at T1 and T4-7 for measurement of blood routine and plasma acute phase reactive protein concentrations. Results Compared with group C, the concentrations of tumor necrosis factor, IL-1β, IL-6, IL-8 and neutrophil elastase in plasma were significantly decreased at T6, 7, the total number of white blood cells, neutrophil count and concentration of plasma acute phase reactive protein were decreased at T7, and duration of stay in intensive care unit was shortened in group P (P<0.05). Conclusion Processing banked suspended RBCs with cell saver before priming can reduce perioperative systemic inflammatory responses of infants undergoing cardiac surgery under CPB. Key words: Erythrocytes; Cardiopulmonary bypass; Inflammation; Infant

Agreement among magnetic resonance imaging / magnetic resonance cholangiopancreatography (MRI-MRCP) and endoscopic ultrasound (eus) in the evaluation of morphological features of branch duct intraductal papillary mucinous neoplasm (BD-IPMN)

The aim was to evaluate the relationship between failure of gut barrier function, inflammatory markers and septic complications after pancreatoduodenectomy for pancreatic adenocarcinoma.44 patients were enrolled in this prospective observational clinical study and underwent curative open pancreatoduodenectomy for adenocarcinoma of the head of the pancreas. All patients underwent assessment of intestinal permeability using the lactulose/manitol excretions ratios (L/M ratio), endotoxemia, IL-1β, IL-6, CRP, and elastase levels before surgery and on postoperative days 1, 3 and 7. Septic complication was defined as a specific clinical condition related to infection by bacterium, virus, or fungus in a specific organ/compartment with positive culture.Septic complications developed in 25% of patients. There were no significant differences in preoperative L/M ratio, endotoxine, CRP, IL-1β, IL-6, and elastase levels between sepsis-positive and sepsis-negative groups. All patients showed a significant increase in intestinal permeability, endotoxemia, IL-1, IL-6, CRP and elastase on the first postoperative day. At postoperative day 7, the sepsis-positive group continued to demonstrate an increase in intestinal permeability, endotoxemia and elastase; a significant difference was observed between the two groups (P = 0.02), whereas there was no significant difference in IL-1, IL-6, and CRP levels.The pattern of change of intestinal permeability, systemic endotoxemia, and elastase concentration in the postoperative period is significantly higher in patients in whom sepsis develops, while the concentration of IL-1β, IL-6 and CRP do not permit to distinguish infection from inflammation.

Efficacy of individualised diets in patients with irritable bowel syndrome: a randomised controlled trial

BackgroundPatients with irritable bowel syndrome (IBS) are often placed on diets guided by food intolerance assays, although these have not been validated. We assessed the effects of individualised diets in...

Lung-protective effect of lung-protective ventilation combined with pressure-controlled ventilation-volume guaranteed in elderly patients undergoing one-lung ventilation

Objective To evaluate the lung-protective effect of lung-protective ventilation(LPV)combined with ventilatory mode pressure-controlled ventilation-volume guaranteed(PCV-VG)in elderly patients undergoing one-lung ventilation(OLV). Methods Eighty American Society of Anesthesiologists physical statusⅠ-Ⅲ patients, aged 65-80 yr, with body mass index of 15-28 kg/m2, scheduled for elective radical resection for esophageal cancer performed via video-assisted thoracoscope, were divided into 4 groups(n=20 each)using a random number table: control group(group C), PCV-VG group, LPV group and LPV combined with PCV-VG group(group LPV+ PCV-VG). At 20 min after changing the body position during two-lung ventilation(T1), 30 min of OLV(T2)and 20 min after restoration of two-lung ventilation(T3), blood samples were collected from the radial artery for blood gas analysis and for determination of peak airway pressure(Ppeak), mean airway pressure(Pmean)and dynamic lung compliance(Cdyn). Alveolar-arterial oxygen gradient, intrapulmonary shunt(Qs/Qt), dead space fraction(Vd/VT)and respiratory index were calculated at T2.Blood samples were collected from the radial artery before induction of anesthesia and at the end of operation for determination of plasma neutrophil elastase(NE)concentrations by enzyme-linked immunosorbent assay.The Clinical Pulmonary Infection Score(CPIS)was assessed at 1 and 7 days after operation, and the development of pulmonary complications such as respiratory failure, pulmonary atelectasis and pulmonary infection was recorded within 7 days after operation. Results Compared with group C, Ppeak was significantly decreased, and Pmean was increased in group PCV-VG, Ppeak and PaCO2 were significantly increased and pH value, Vd/VT and Qs/Qt were decreased in group LPV, Ppeak, Vd/VT, Qs/Qt, pH value and postoperative CPIS were significantly decreased, and Pmean, Cdyn and PaO2 were increased in group LPV+ PCV-VG, and the NE concentration at the end of operation was significantly decreased in PCV-VG, LPV and LPV+ PCV-VG groups(P<0.05). Compared with group PCV-VG, Pmean, Cdyn and PaO2 were significantly increased, and pH value, Qs/Qt, NE concentration at the end of operation and CPIS were decreased in group LPV+ PCV-VG(P<0.05). Compared with group LPV, Ppeak, Qs/Qt, NE concentration at the end of operation and CPIS were significantly decreased, and Cdyn was increased in group LPV+ PCV-VG(P<0.05). Pulmonary complications such as respiratory failure, pulmonary atelectasis and pulmonary infection were not observed after operation in the four groups. Conclusion LPV combined with PCV-VG can optimize the lung-protective effect in elderly patients undergoing OLV. Key words: Respiration, artificial; Aged

Coeliac disease in infants: antibodies to deamidated gliadin peptide come first!

BackgroundThe onset of coeliac disease (CD) in the first year of life is uncommon and the diagnosis can be challenging due to the suboptimal sensitivity of tissue transglutaminase antibodies (tTG) at this age and the many other possible causes of malabsorption in infants. Antibodies to deamidated gliadin peptides (anti-DGPs), especially IgG, may appear earlier than IgA anti-tTG in very young children with CD.Case presentationWe report here on an 8-month-old child who was evaluated for failure to thrive, constipation and developmental delay. The symptoms started following gluten introduction in the diet. Laboratory tests showed high fecal elastase concentration, normal serum IgA levels with positive IgG and IgA anti-DGPs, whereas anti-tTG were not detected. The duodenal biopsy revealed a complete villous atrophy (Marsh-Oberhuber 3C). The culture of biopsy fragments in the presence of gliadin peptides did not stimulate the production of IgA anti-endomysial antibodies. Genetic testing proved the child was positive for HLA-DQ2 (DQA1*05; DQB1*02) and HLA-DQ8 (DQA1*03, DQB1*0302). Having initiated the gluten-free diet, the symptoms disappeared and the infant experienced rapid catch-up growth with normalization of psychomotor development.ConclusionsThis case report highlights the utility of anti-DGPs for screening infants with suspected CD. The pattern with positivity for IgG and IgA anti-DGPs only is rare in IgA-competent children with biopsy-proven CD. It could be explained in infancy as immaturity of the adaptive immune system.

NPS 2143, a selective calcium-sensing receptor antagonist inhibits lipopolysaccharide-induced pulmonary inflammation

NPS 2143, a novel and selective antagonist of calcium-sensing receptor (CaSR) has been reported to possess anti-inflammatory activity. In the present study, we examined the protective effect of NPS 2143 on lipopolysaccharide (LPS)-induced acute lung injury (ALI). NPS 2143 pretreatment significantly inhibited the influx of inflammatory cells and the expression of monocyte chemoattractant protein-1 (MCP-1) in the lung of mice with LPS-induced ALI. NPS 2143 decreased the levels of neutrophil elastase (NE) and protein concentration in the bronchoalveolar lavage fluid (BALF). NPS 2143 also reduced the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF and serum. In addition, NPS 2143 attenuated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and increased the activation of AMP-activated protein kinase (AMPK) in the lung. NPS 2143 also downregulated the activation of nuclear factor-kappa B (NF-κB) in the lung. In LPS-stimulated H292 airway epithelial cells, NPS 2143 attenuated the releases of IL-6 and MCP-1. Furthermore, NPS 2143 upregulated the activation of AMPK and downregulated the activation of NF-κB. These results suggest that NPS 2143 could be potential agent for the treatment of inflammatory diseases including ALI.

Septic Complications after Resection for Middle or Low Rectal Cancer: Role of Gut Barrier Function and Inflammatory Serum Markers

Background: The focus of this study was to understand the relationship between the failure of gut barrier function, inflammatory markers and septic complications after resection for extraperitoneal rectal cancer. Methods: One hundred seven patients were enrolled into this prospective observational study and underwent open colorectal resection for extraperitoneal cancer. All patients underwent an assessment of intestinal permeability (L/M ratio), endotoxemia, interleukin-1β (IL-1β), interleukin-6 (IL-6), C-reactive protein (CRP) and elastase levels before surgery and on postoperative days 1, 3, and 7. Results: Septic complications developed in 23.3% of patients. There were no significant differences in preoperative L/M ratio, endotoxine, CRP, interleukin-1 (IL-1), IL-6, and elastase levels between septic and non-septic groups. All patients showed a significant increase in intestinal permeability, endotoxemia, IL-1, IL-6, CRP, and elastase on the first postoperative day. At postoperative day 7, the septic group continued to demonstrate an increase in intestinal permeability, endotoxemia and elastase and significant difference was observed between the 2 groups (p < 0.05), whereas there was no significant difference in IL-1, IL-6, and CRP levels. Conclusion: The pattern of change in the postoperative period of intestinal permeability, systemic endotoxemia and elastase concentration is significantly higher in patients in whom sepsis develops, while the concentration of IL-1β, IL-6, and CRP does not permit to distinguish infection from inflammation.

The effect of primary hyperparathyroidism on pancreatic exocrine function.

Elastase-1 is a proteolytic enzyme secreted by pancreatic acinar cells, and measurements of the concentration this enzyme are used to evaluate pancreatic exocrine function. We aimed to determine whether pancreatic exocrine function declines due to chronic hypercalcemia by measuring fecal elastase levels. 75 patients with primary hyperparathyroidism (18 men and 47 women) and 30 healthy subjects (11 men and 19 women) participated in this study. Renal function tests, lipid parameters, bone mineral density, and serum calcium, phosphorus, vitamin D, parathormone, glucose, and thyroid stimulating hormone levels as well as fecal elastase concentrations, were determined in these patients and controls. The mean fecal elastase level was 335.3±181.4μg/g in the PHPT group and 317.4±157.3μg/g in the control group. There was no significant difference in fecal elastase levels between the two groups (p=0.5). Chronic hypercalcemia in primary hyperparathyroidism did not decrease the fecal elastase level, which is an indirect indicator of chronic pancreatitis; therefore, chronic hypercalcemia in PHPT may not cause chronic pancreatitis.

Intestinal permeability changes, systemic endotoxemia, inflammatory serum markers and sepsis after Whipple's operation for carcinoma of the pancreas head

PourposeThe aim was to evaluate the relationship between failure of gut barrier function, inflammatory markers and septic complications after pancreatoduodenectomy for pancreatic adenocarcinoma. Methodology44 patients were enrolled in this prospective observational clinical study and underwent curative open pancreatoduodenectomy for adenocarcinoma of the head of the pancreas. All patients underwent assessment of intestinal permeability using the lactulose/manitol excretions ratios (L/M ratio), endotoxemia, IL-1β, IL-6, CRP, and elastase levels before surgery and on postoperative days 1, 3 and 7. Septic complication was defined as a specific clinical condition related to infection by bacterium, virus, or fungus in a specific organ/compartment with positive culture. ResultsSeptic complications developed in 25% of patients. There were no significant differences in preoperative L/M ratio, endotoxine, CRP, IL-1β, IL-6, and elastase levels between sepsis-positive and sepsis-negative groups. All patients showed a significant increase in intestinal permeability, endotoxemia, IL-1, IL-6, CRP and elastase on the first postoperative day. At postoperative day 7, the sepsis-positive group continued to demonstrate an increase in intestinal permeability, endotoxemia and elastase; a significant difference was observed between the two groups (P = 0.02), whereas there was no significant difference in IL-1, IL-6, and CRP levels. ConclusionThe pattern of change of intestinal permeability, systemic endotoxemia, and elastase concentration in the postoperative period is significantly higher in patients in whom sepsis develops, while the concentration of IL-1β, IL-6 and CRP do not permit to distinguish infection from inflammation.

Blood Plasma Concentration and Activity of Pancreatic Lipase, Pancreatic Trypsin, MMP‐9, and Elastase in Congestive Heart Failure

Recent evidence suggests that pancreatic digestive enzymes may be involved in several types of organ dysfunction. This may include heart disease, but no studies exist. We hypothesize that pancreatic trypsin, pancreatic lipase, MMP‐9, and elastase may be present in blood and cardiac muscle in patients with congestive heart failure (CHF). Pancreatic enzymes may leak out of the small intestinal lumen, enter the systemic circulation and, ultimately, cause damage of the heart muscle. Pancreatic proteases, such as trypsin, are capable of activating other proteases, such as MMP‐9. Blood was drawn from 20 patients (10 CHF and 10 non‐CHF patients) while at rest. Western Blots showed a significant increase in plasma pancreatic lipase, trypsin, and MMP‐9 levels for the CHF patients when compared to non‐CHF patients. Activity assay results showed a significant increase in plasma MMP‐2/9 activity levels in CHF compared to non‐CHF patients but no differences in trypsin and elastase activity. These pilot experiments suggest that elevated plasma trypsin, lipase, and MMP‐9 concentrations as well as plasma MMP2/9 activity are correlated with CHF, may play a role in the loss of cardiac function, and may serve as potential biomarkers for CHF.Support or Funding InformationNIH Grants: 5 R01 HL073355‐01, GM 85072

The Effects of High-Concentration Oxygen on Inflammatory Markers in Laparoscopic Cholecystectomy: A Randomized Controlled Trial.

This study assessed effect of administration of high-concentration supplemental perioperative oxygen on systemic inflammatory and immune response in patients undergoing elective laparoscopic cholecystectomy. One hundred seventy-seven patients were assigned randomly to an oxygen/air mixture with a fraction of inspired oxygen (FiO2) of 30% (n=88) or 80% (n=89). White blood cells, peripheral lymphocytes subpopulation, human leukocyte antigen-DR, neutrophil elastase, interleukin (IL)-1 and IL-6, and C-reactive protein were investigated. Significantly higher concentration of neutrophil elastase, IL-1, IL-6 and C-reactive protein was detected postoperatively in the 30% FiO2 group patients in comparison with the 80% FiO2 group (P<0.05). Statistically significant change in human leukocyte antigen-DR expression was recorded postoperatively at 24 hours, as a reduction of this antigen expressed on monocyte surface in patients from 30% FiO2 group. This study demonstrated that high-concentration (80%) supplemental perioperative oxygen can lead to a reduction in postoperative inflammatory response and avoid postoperative immunosuppression.

Detection of human elastase isoforms by the ScheBo Pancreatic Elastase 1 Test.

Determination of fecal pancreatic elastase content by ELISA is a reliable, noninvasive clinical test for assessing exocrine pancreatic function. Despite the widespread use of commercial tests, their exact molecular targets remain poorly characterized. This study was undertaken to clarify which human pancreatic elastase isoforms are detected by the ScheBo Pancreatic Elastase 1 Stool Test and whether naturally occurring genetic variants influence the performance of this test. Using recombinantly expressed and purified human pancreatic proteinases, we found that the test specifically measured chymotrypsin-like elastases (CELA) 3A and 3B (CELA3A and CELA3B), while CELA2A was not detected. Inactive proelastases, active elastases, and autolyzed forms were detected with identical efficiency. CELA3B elicited approximately four times higher ELISA signal than CELA3A, and we identified Glu154 in CELA3B as the critical determinant of detection. Common genetic variants of CELA3A and CELA3B had no effect on test performance, with the exception of the CELA3B variant W79R, which increased detection by 1.4-fold. Finally, none of the human trypsin and chymotrypsin isoforms were detected. We conclude that the ScheBo Pancreatic Elastase 1 Stool Test is specific for human CELA3A and CELA3B, with most of the ELISA signal attributable to CELA3B.NEW & NOTEWORTHY The ScheBo Pancreatic Elastase 1 Stool Test is widely used to assess pancreatic exocrine function, yet its molecular targets have been poorly defined. We demonstrate that, among the human pancreatic proteinases, the test measures the elastase isoform CELA3B and, to a lesser extent, CELA3A. Genetic variants of the human CELA3 isoforms have no significant effect on test performance.

A Novel Modification of the Murine Elastase Infusion Model of Abdominal Aortic Aneurysm Formation

To create a novel procedure that will decrease the mortality of experimental animals in the intraarterial infusion of elastase abdominal aortic aneurysm (AAA) model. Novel models were created by means of direct puncture in the infrarenal abdominal aortic aorta, intraluminal elastase in the 1-cm segment of abdominal aorta. Femoral artery cannula approach and infusing with elastase was considered as the traditional group and that infusing with saline solution as the control group. Survival rate, morphology and histology of aneurysms, and inflammation mediators were calculated. Among the 36 rats, the average length from testicular arteries to left iliolumbar artery was 1.18±0.22cm, and 77.8% of them were longer than 1cm. Procedure time was significantly shorter in novel group than that in 2 other groups (P=0.006; P<0.0001). During 24hr postoperation, no death was observed in the novel group. Within 4 wk, survival rate in the control group was 60.6% and 80.8% in the novel group whereas 41.0% in the traditional group. Till the second week, all rats in the traditional and novel group had formed AAAs. And then, the survival rates and rupture rates of AAA between the 2 groups were similar within the following 2 wk (P=0.487; P=0.539). Inflammation degree and elastase content in intima media of aneurysms were similar (P=0.720). However, Tumor necrosis factor alpha and Interleukin-1 beta levels were significantly lower in the novel group than those in the traditional group (P<0.0001; P<0.0001). A novel rat AAA model was created by intraluminal elastase infusion through direct puncture the infrarenal aorta. This model is efficient and reliable, with a high survival rate and with similar morphology and histology of aortic aneurysms.

Complement effectors, C5a and C3a, in cystic fibrosis lung fluid correlate with disease severity.

In cystic fibrosis (CF), lung damage is mediated by a cycle of obstruction, infection, inflammation and tissue destruction. The complement system is a major mediator of inflammation for many diseases with the effectors C5a and C3a often playing important roles. We have previously shown in a small pilot study that CF sputum soluble fraction concentrations of C5a and C3a were associated with clinical measures of CF disease. Here we report a much larger study of 34 CF subjects providing 169 testable sputum samples allowing longitudinal evaluation comparing C5a and C3a with clinical markers. Levels of the strongly pro-inflammatory C5a correlated negatively with FEV1% predicted (P < 0.001), whereas the often anti-inflammatory C3a correlated positively with FEV1% predicted (P = 0.01). C5a concentrations correlated negatively with BMI percentile (P = 0.017), positively with worsening of an acute pulmonary exacerbation score (P = 0.007) and positively with P. aeruginosa growth in sputum (P = 0.002). C5a levels also correlated positively with concentrations of other sputum markers associated with worse CF lung disease including neutrophil elastase (P < 0.001), myeloperoxidase activity (P = 0.006) and DNA concentration (P < 0.001). In contrast to C5a, C3a levels correlated negatively with worse acute pulmonary exacerbation score and correlated negatively with sputum concentrations of neutrophil elastase, myeloperoxidase activity and DNA concentration. In summary, these data suggest that in CF sputum, increased C5a is associated with increased inflammation and poorer clinical measures, whereas increased C3a appears to be associated with less inflammation and improved clinical measures.