Pancreatic Lipase Concentrations Research Articles

Cardiac biomarker concentrations in cats with elevated pancreatic lipase concentrations.

Cardiac biomarker concentrations are elevated in dogs with pancreatitis, but it is unknown if this is also the case for cats. The serum feline pancreatic lipase immunoreactivity (fPLI) of serum samples from 60 cats was quantified using the Spec fPL assay. Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (HST) concentrations were also measured using commercial assays. Five of 20 cats with fPLI concentrations of 8.8mg/L or more had above reference interval NT-proBNP concentrations. Serum NT-proBNP concentrations were not correlated with fPLI concentrations (p = 0.31) and were not different in each diagnostic category for fPLI results (p = 0.24). Serum HST concentrations were positively correlated with fPLI concentrations (r = 0.278, 95% confidence interval: 0.02‒0.50, p = 0.03). However, they were not significantly different in each diagnostic category for fPLI results (p = 0.16). Unidentified co-variates could contribute to the association between fPLI and cardiac biomarker concentrations. Cats with elevated fPLI concentrations may have elevated cardiac biomarker concentrations.

Ursolic Acid Inhibited Cholesterol Esterase and Pancreatic Lipase Activities and Decreased Micellar Cholesterol Solubility In Vitro

Ursolic acid (UA) is a natural triterpene carboxylic acid with an underlying anti-hyperlipidemia effect. This study examined the mechanism of interactions of UA with cholesterol esterase (CEase), pancreatic lipase (PL), and micellar cholesterol solubility in vitro. The half-maximal inhibitory concentration (IC50) of CEase, PL, and micellar cholesterol solubility was determined to be 0.07 ± 0.01 mg/mL, 1.81 ± 0.13 mg/mL, and 1.73 ± 0.08 mg/mL, respectively. Multispectral combination revealed that UA changed the secondary structure and quenched the intrinsic fluorescence by static quenching of the two enzymes. The interactions were exothermic reaction as determined by enthalpy. Furthermore, molecular docking confirmed that UA was bound to amino acids of two enzymes at active site through hydrophobic interaction and van der Waals forces. Molecular dynamics (MD) simulation found that CEase and PL rearranged with UA to form stable complexes. The strong inhibition effect of CEase and PL mediated by UA might provide additional insight into understanding the role of UA in the hypolipidemic effect.

Serum calcium concentrations are inversely correlated with pancreatic lipase concentrations in dogs.

(1) Determine if a relationship exists between ionized calcium (iCa) and pancreatic lipase (cPLI) concentration in dogs, and (2) assess for correlation between resolving hypercalcemia and cPLI concentrations in dogs after treatment for primary hyperparathyroidism (PHPT). Phase I, 44 residual serum samples (collected April 2023) from client-owned dogs with a clinical indication for cPLI quantification. Phase II, 24 residual serum samples (collected August 2022 through February 2023) from client-owned dogs with PHPT pre- and postcorrection of hypercalcemia. Serum cPLI and iCa concentrations were measured via the Spec cPL assay and a spectrophotometric method respectively. Spearman's rank correlation coefficients were used to investigate if there was a correlation between serum calcium and cPLI concentrations. A paired t-test was used to investigate the effect of the resolution of hypercalcemia on serum cPLI concentrations. Phase I, serum cPLI concentrations were negatively correlated with serum iCa concentrations (r = -.429, 95% CI [-.64, -.14], P = .005) in dogs with a clinical indication for cPLI quantification. Phase II, median serum cPLI concentrations were higher before (median: 228.5 μg/L, IQR: 351.3 μg/L) than after (median: 141.0 μg/L, interquartile ranges (IQR): 279.5 μg/L) management of hypercalcemia (PHPT model). However, the decrease in cPLI concentration was not statistically significant (P = .70). Calcium depletion may result in an inverse relationship between serum cPLI and iCa concentrations in dogs with a clinical indication for cPLI quantification. Hypercalcemia may be associated with an above reference interval cPLI concentration in some dogs.

Evaluation of red blood cell distribution width, neutrophil-to-lymphocyte ratio, and other hematologic parameters in canine acute pancreatitis.

To determine if RBC distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and other hematological parameters are associated with increased odds of in-hospital mortality, increased length of hospitalization (LOH), or disease severity as measured by the Canine Acute Pancreatitis Severity (CAPS) score in dogs with acute pancreatitis (AP). Retrospective, multicenter study from January 2016 to August 2020. Four private emergency and specialty referral centers. On initial case search, 118 client-owned dogs were identified with a clinical diagnosis of AP. Out of these cases, 114 dogs met inclusion criteria, defined as sudden onset of ≥2 compatible clinic signs (lethargy, anorexia, vomiting, or abdominal pain), a specific canine pancreatic lipase concentration >400μg/L, hospital admission, as well as CBC and serum biochemistry run within 48hours of initial hospitalization. Disease severity was calculated and measured using the CAPS score, in addition to LOH and in-hospital mortality. None. Clinical endpoints were in-hospital mortality, LOH, and disease severity, as evaluated by the CAPS score. Overall in-hospital mortality was 36.8%. NLR was significantly associated with survival, with a higher percentage being associated with an increased likelihood of nonsurvival (odds ratio: 1.1, 95% confidence interval: 1.0-1.2; P=0.006, adjusted P=0.04). Increased NLR was found to be significantly associated with a longer LOH based on the unadjusted P-value (P=0.02) but was not statistically significant based on a P-value adjusted for multiple comparisons (P=0.12). No significant associations were noted when RDW, platelet-to-lymphocyte ratio, WBC count, mean platelet volume, RDW-to-platelet ratio, or RDW-to-total serum calcium ratio was evaluated against outcome measures. This study retrospectively evaluated the prognostic utility of several readily available hematological parameters in dogs hospitalized for AP. Dogs with an increased NLR may have a higher risk of in-hospital mortality and increased LOH, although future prospective studies are necessary to confirm these findings.

Understanding lipase assays in the diagnosis of pancreatitis in veterinary medicine.

Pancreatitis commonly occurs in humans, dogs, and cats. For both veterinary and human health-care professionals, measurement of serum pancreatic lipase concentration or activity provides useful support for a diagnosis of pancreatitis. In this Currents in One Health manuscript, we will discuss commonly used lipase assays in veterinary medicine, namely catalytic colorimetric and immunological lipase assays. We highlight potential diagnostic pitfalls associated with analytical specificity, assay validation, and sample condition interferences. Catalytic lipase assays may detect extrapancreatic lipases. In addition, we propose a decision tree for interpretation of lipase assays in the context of a clinical patient.

Risk Factors and Clinical Presentation in Dogs with Increased Serum Pancreatic Lipase Concentrations-A Descriptive Analysis.

Simple SummaryOver the past several years, there has been an increasing importance placed on clinical presentation as part of a diagnosis of pancreatitis, and yet there is comparatively little data investigating the full array of clinical signs that may be seen in dogs with pancreatitis. Our study showed that dogs with increased pancreatic lipase immunoreactivity concentrations could display a wide range of clinical signs, which may be related to pancreatitis or a concurrent disease. Non-specific clinical signs, such as anorexia, were prevalent. Additionally, overt abdominal pain was infrequently reported, and veterinarians should be cautious in ruling out pancreatitis due to a lack of abdominal pain alone. Additionally, limited data is available on potential risk factors for pancreatitis in dogs; this information could be important in the development of disease prevention strategies. In our study, the most common concurrent disease was hepatobiliary abnormalities. Additional studies are needed to determine whether this is a causative or associative relationship. Drug use reflected common prescribing practices, and anti-epileptic drug use was low despite prior studies documenting clear associations between phenobarbital and potassium bromide and drug-associated pancreatitis. Adult maintenance diets, in addition to human foods and dog treats, were commonly fed prior to the development of an increased pancreatic lipase concentration.Limited data exist regarding the full array of clinical signs seen in dogs with pancreatitis and potential risk factors for the disease. Laboratory submissions from the Gastrointestinal Laboratory at Texas A&M University were retrospectively reviewed for dogs with an increased serum pancreatic lipase immunoreactivity (cPLI) concentration (≥400 µg/L), and an internet-based survey was distributed to the attending veterinarian and/or technician on each case. The survey contained questions related to (i) clinical signs, (ii) prior gastrointestinal upset, (iii) comorbidities, (iv) pre-existing medical therapies, and (v) dietary history. One hundred and seventy (170) survey responses were recorded. The top three clinical signs reported were inappetence (62%), diarrhea (53%), and vomiting (49%). Abdominal pain was noted in only 32% of dogs, likely associated with poor pain detection. Additionally, the majority of dogs (71%) had prior episodes of gastrointestinal upset within the past 12 months, lending support for the commonality of recurrent acute pancreatitis, or acute on chronic disease. Hepatobiliary abnormalities (24%) were the most common concurrent disease, and endocrine disorders were seen in a low proportion of respondents (5–8%). Adult maintenance diets (65%), dog treats (40%), and human foods (29%) were commonly consumed by dogs prior to the discovery of increased cPLI concentration.

The Agreement between Feline Pancreatic Lipase Immunoreactivity and DGGR-Lipase Assay in Cats-Preliminary Results.

Simple SummaryFeline pancreatitis is a common disease with diagnostics requiring a combination of clinical, laboratory and imaging methods. Measuring of pancreatic lipase concentration is the laboratory mainstay of feline pancreatitis diagnostics. It can be done using immunoenzymatic assay (feline pancreatic immunoreactivity, fPLI) or colorimetric assay based on hydrolyzing a special substrate (DGGR) to a color product. A DGGR-lipase assay is manufactured by various companies. Studies carried out in cats on the DGGR-lipase assay of a single manufacturer have shown a high agreement with fPLI, however studies in dogs indicate that the performance of assays of different manufacturers may vary considerably. One of the largest Polish veterinary laboratories working 24/7 in the largest Polish cities offers the DGGR-lipase assay of a large Polish laboratory solutions provider. The values obtained in this assay are higher than those yielded by the traditional DGGR-lipase assay validated in studies carried out so far. Therefore, we decided to evaluate the agreement between the DGGR-lipase assay of the Polish manufacturer and fPLI. The agreement proved to be as high as for the traditional assay.The colorimetric catalytic assay based on the use of 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) (DGGR) ester as a substrate for pancreatic lipase activity is commonly used for the diagnosis of pancreatitis in dogs and cats. Even though the assay has generally been shown to yield consistent results with feline pancreatic lipase immunoreactivity (fPLI) assay, the agreement may vary between assays of different manufacturers. In this study, the chance-corrected agreement between a DGGR-lipase assay offered by one of the biggest providers of diagnostic solutions in Poland and fPLI assay was investigated. The study was carried out on 50 cats in which DGGR-lipase activity and fPLI were tested in the same blood sample. The chance-corrected agreement was determined using Gwet’s AC1 coefficient separately for the fPLI assay’s cut-off values of >3.5 μg/L and >5.3 μg/L. The DGGR-lipase activity significantly positively correlated with fPLI (Rs = 0.665; CI 95%: 0.451, 0.807, p < 0.001). The chance-corrected agreement between the fPLI assay and DGGR-lipase assay differed considerably depending on the cut-off values of the DGGR-lipase assay. When the cut-off value reported in the literature (>26 U/L) was used, it was poor to fair. It was moderate at the cut-off value recommended by the laboratory (>45 U/L), and good at the cut-off value recommended by the assay’s manufacturer (>60 U/L). The highest agreement was obtained between the fPLI assay at the cut-off value of 3.5 μg/L and the DGGR-lipase assay at the cut-off value of 55 U/L (AC1 = 0.725; CI 95%: 0.537, 0.914) and between the fPLI assay at the cut-off value of 5.3 μg/L and the DGGR-lipase assay at the cut-off value of 70 U/L (AC1 = 0.749; CI 95%: 0.577, 0.921). The study confirms that the chance-corrected agreement between the two assays is good. Prospective studies comparing both assays to a diagnostic gold standard are needed to determine which of them is more accurate.

Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients

IntroductionHeart failure is associated with degradation of cell functions and extracellular matrix proteins, but the trigger mechanisms are uncertain. Our recent evidence shows that active digestive enzymes can leak out of the small intestine into the systemic circulation and cause cell dysfunctions and organ failure.MethodsAccordingly, we investigated in morning fasting plasma of heart failure (HF) patients the presence of pancreatic trypsin, a major enzyme responsible for digestion.ResultsWestern analysis shows that trypsin in plasma is significantly elevated in HF compared to matched controls and their concentrations correlate with the cardiac dysfunction biomarker BNP and inflammatory biomarkers CRP and TNF-α. The plasma trypsin levels in HF are accompanied by elevated pancreatic lipase concentrations. The trypsin has a significantly elevated activity as determined by substrate cleavage. Mass spectrometry shows that the number of plasma proteins in the HF patients is similar to controls while the number of peptides was increased about 20% in HF patients. The peptides are derived from extracellular and intracellular protein sources and exhibit cleavage sites by trypsin as well as other degrading proteases (data are available via ProteomeXchange with identifier PXD026332).ConnclusionsThese results provide the first evidence that active digestive enzymes leak into the systemic circulation and may participate in myocardial cell dysfunctions and tissue destruction in HF patients.ConclusionsThese results provide the first evidence that active digestive enzymes leak into the systemic circulation and may participate in myocardial cell dysfunctions and tissue destruction in HF patients.

Replacement of fish oil by soybean oil and microalgal meals in diets for Totoaba macdonaldi (Gilbert, 1890) juveniles

The objective of this study was to evaluate the use of soybean oil (SO) and two microalgal meals derived from Schizochytrium limacinum (SL1 and SL2) to replace fish oil (FO) in diets for Totoaba macdonaldi juveniles. Nine isoproteic (54% crude protein, CP) and isolipidic (14% crude fat, CF) diets were formulated based on a 3 × 3 factorial design, using the three lipid sources and three replacement levels, 33%, 66% and 100%. A control diet containing FO as the main lipid source served as a reference. Diets were fed for 6 weeks and were randomly assigned to six replicate tanks of a recirculating aquaculture system, with 25 fish stocked per tank. Initial mean fish weight was 8.08 g; at the end of the trial, statistical differences for growth responses such as weight gain (WG; P = 0.0069) and thermal growth coefficient (TGC; P = 0.0027) were detected. WG (SL1 = 50.75 g, SL2 = 51.43 g) and TGC (0.148) of fish fed the S. limacinum meals were significantly higher than in those fed SO (WG = 41.13 g; TGC = 0.129). Conversely, the hepatosomatic index (HSI; P = 0.0009) of fish fed SO was significantly higher (1.38%) compared to those fed the microalgae meals (SL1 = 1.13%, SL2 = 1.22%). Also, proximate composition of liver was significantly influenced by the lipid source and CF was significantly higher (P = 0.0067) in fish fed SO (47.68%) than in fish fed SL1 (37.44%) or SL2 (39.86%). The fatty acid (FA) profile of muscle and liver reflected the dietary FA composition; SO prompted increased concentrations of 18:2n-6 and total n-6 FA in fish fillet; whereas, the S. limacinum meals increased 22:6n-3, total n-3 FA and the n-3/n-6 ratios, which is highly desirable in food destined for human consumption. In addition, the concentration of pancreatic lipase 1 (70.2 kDa) in anterior intestine and pyloric caeca of fish significantly decreased (P = 0.0019) from 2.93 to 1.85 mg g−1 as the level of FO replaced increased. These findings indicate that up to 100% of FO can be replaced by S. limacinum meals improving the growth of T. macdonaldi and preserving the nutritional value and the health benefits of the fillet for human consumption; whereas, SO decreased growth and the concentration of 22:6n-3, 20:5n-3, total n-3, and n-3/n-6 ratios, while increasing the HSI and the risk of hepatic dysfunction and steatosis.

Estimates of biologic variation in specific feline pancreatic lipase concentrations in cats without clinical or ultrasonographic evidence of pancreatitis.

Serum concentrations of feline-specific pancreatic lipase are commonly used for diagnosis and monitoring of pancreatitis in cats, but little is known regarding biologic variation of this analyte. The purpose of the study was to determine biologic variation, index of individuality, and reference change values (RCV) for specific feline pancreatic lipase concentrations (Spec fPL) in apparently healthy cats. Four blood samples were collected prospectively from 12 apparently healthy cats at 2-week intervals. The Spec fPL was measured in all serum samples by a reference laboratory. Intra-individual variation for Spec fPL was 33.5% (95% CI 27.1-43.8%); inter-individual variation was 99.9% (69.2-169.9%) and analytic variation was 7.3% (6.1-9.2%). Reciprocal index of individuality for Spec fPL was 2.9 (2.5-3.8), the 2-sided RCV was 95.1% (77.0-123.9%). Due to high individuality, use of a population-based RI for Spec fPL may fail to detect clinically significant elevations in individual cats. The use of subject-based RIs for Spec fPL may have greater sensitivity for the detection of a change in pancreatic physiology in cats; however, this would require serial assessment of apparently healthy cats.

Mechanics and surface ultrastructure changes of poly(3-hydroxybutyrate) films during enzymatic degradation in pancreatic lipase solution

ABSTRACTA study of in vitro biodegradation of poly(3-hydroxybutyrate) (PHB) in model conditions was performed. The porcine pancreatic lipase solutions at different concentrations in the two buffer systems (phosphate-buffered saline (PBS) and simulating body fluid (SBF)) were chosen as model biodegradation media. At first, optimal concentration of pancreatic lipase (0.25 mg/ml in PBS) was determined: in these media the decomposition of PHB films realized faster according to the data of gravimetric analysis. Differential scanning calorimetry showed an increase in the crystallinity of the samples (from 49% to 59%) after enzymatic degradation. These data are confirmed by method of nanoindentation, where the increase of the Young's modulus during the degradation (from 1.37 GPa to 4.4 GPa) was shown. This is due to the crystallization of the amorphous polymer component, and its decomposition and dissolving. During biodegradation three types of polymer ultrastructure changes were observed on the surfaces of the films: appearance of new lamellae, disappearance of lamellae and disintegration of lamellae into shorter fragments.

Influence of dietary lipid on growth performance and body composition of the Gulf corvina, Cynoscion othonopterus

Based upon an iso-proteic dietary content of 40%, a 56-day experiment was conducted to evaluate the effects of incremental levels of dietary crude fat (2, 5, 8, 11, 14, 17, 20, 23 and 26%) on the performance of Cynoscion othonopterus juveniles, with an initial mean body weight of 32.86±0.48g. Fish were reared in a clear-water, recirculating culture system, composed of 48 circular tanks of 250L (0.4m2 bottom area) filled with 200L filtered seawater, at a density of 3fish tank−1 (15fishm−3), assigning each treatment to five replicate tanks. Fish were fed approximately 3% of their wet body weight daily. Overfeeding was minimized while maintaining the feeding rate close to apparent satiation, dividing the daily ration into three equal portions. A clear dose–response effect of dietary crude fat was observed on growth of the Gulf corvina, C. othonopterus, with the best results corresponding to fish fed 11% crude fat, while growth performance was reduced as dietary crude fat departed from this level. These results were significant for specific growth rate and thermal growth coefficient data (P=0.0283 and 0.0450, respectively), and although not statistically significant, the same pattern held true numerically for the majority of the other growth response variables and feed utilization indices measured. Quadratic broken line analysis of thermal growth coefficient data estimated a requirement for dietary crude fat of 11.4% for this species, with 95% confidence interval of 9.8 to 13.0%. Significantly increased lipid deposition, concomitant with reduced moisture content in muscle and whole body were observed in response to incremental levels of dietary crude fat. Intestine pancreatic lipase content tended to decrease with increasing dietary crude fat level, although this pattern was not statistically significant. Statement of relevanceThe present manuscript provides the first documented data on lipid nutrition of the Gulf corvina, a novel candidate species for aquaculture in Northwest Mexico. Significantly increased lipid deposition, concomitant with reduced moisture content in muscle and whole body, were observed in response to incremental levels of dietary lipid. A clear dose–response effect of dietary crude fat was observed on growth, with an estimated requirement for dietary crude fat of 11.4%, when fed a diet containing 40% crude protein.

Glycemic status and predictors of relapse for diabetic cats in remission.

BackgroundIt is unknown if diabetic cats in remission have persistent abnormalities of glucose metabolism and should be considered prediabetic, or have normal glucose tolerance.ObjectiveTo characterize glycemic status of diabetic cats in remission and to determine predictors of relapse.AnimalsA total of 21 cats in diabetic remission and 28 healthy control cats.MethodsAt a median of 107 days after remission, screening blood glucose concentration was measured on entry to the clinic. After a 24‐hour fast in hospital, fasting blood glucose, fructosamine and feline pancreatic lipase concentrations were measured, and 3 hours later, a simplified IV glucose tolerance test (1 g glucose/kg) performed. Twenty cats were monitored for relapse for at least 9 months.ResultsOf the 21 cats in remission, 19% (4/21) had impaired fasting glucose concentration and 76% (16/21) had impaired glucose tolerance. Of cats followed up for 9 months after testing, 30% (6/20) had relapsed and required insulin treatment. Fasting blood glucose concentration ≥7.5 mmol/L (≥135 mg/dL) (odds ratio [OR] = 12.8) and severely impaired glucose tolerance (≥5 hours to return to <6.5 mmol/L or <117 mg/dL; OR = 15.2) were significantly associated with relapse. Blood glucose concentration >14 mmol/L; 252 mg/dL at 3 hours was significantly associated with relapse (OR = 10.1).Conclusion and Clinical ImportanceMost cats in diabetic remission have impaired glucose tolerance and a minority have impaired fasting glucose concentration and should be considered prediabetic. More severe glucose intolerance and impaired fasting glucose concentration are predictors of relapse. Ongoing glucose monitoring of diabetic cats in remission is recommended.

Emulsifier in broiler diets containing different fat sources

This present study aimed at evaluating the effect of the addition of an emulsifier to diets containing soybean oil, poultry fat or their blend, on the performance, carcass traits, serum lipid levels, pancreatic lipase concentration and nutrient digestibility of broilers. A randomized block design was applied using a 3 x 2 factorial arrangement, with three fat sources (soybean oil, poultry fat, and a blend of 50% soybean oil and 50% poultry fat) and the addition or not of an emulsifier. In experiment I, broiler performance, carcass traits, serum cholesterol, HDL, and triglyceride levels, and pancreatic lipase activity in 42-day-old broilers were evaluated. In experiment II, dry matter (DM), ether extract (EE), crude protein (CP) and crude fiber (CF) coefficients of digestibility were analyzed. Broilers fed the diet containing soybean oil and emulsifier presented higher body weight, weight gain and better feed conversion ratio. When birds were fed poultry fat and the fat blend (soybean oil and poultry fat) and the emulsifier was added to the diets, pancreatic lipase concentration increased. It was concluded that the use of soybean oil, poultry fat and their blend does no in the diet does not influence the performance, carcass traits, or serum cholesterol, HDL and triglyceride levels of 42-day-old broilers. The addition of emulsifiers to diets containing poultry fat improves ether extract digestibility and increases the production and secretion of pancreatic lipase.

Analysis of duodenal drainage fluid after cholecystokinin (CCK) stimulation in healthy volunteers.

Hormonal stimulatory agents are used to assess pancreatic function. Biologically derived secretin, the most widely used pancreatic secretagogue, is no longer available in the United States. Existing secretory tests using cholecystokinin alone are cumbersome, requiring a unique dual tube (gastric and duodenal) collection system and constant perfusion of a nonabsorbable marker to calculate enzyme output (in international units [IU]). A simpler, quantitative cholecystokinin stimulation test that measures enzyme concentrations (in international units per liter [IU/L]) instead of total output would obviate need for marker perfusion/collection. The aim of our experiment was to study the secretory patterns of pancreatic enzyme concentration in duodenal fluid after cholecystokinin stimulation in healthy volunteers. Healthy subjects had a Dreiling tube inserted endoscopically into the ligament of Treitz. Gastric and duodenal aspiration ports were connected to low intermittent suction. A 20-minute baseline was obtained to clear the gastric and duodenal lumina of residual fluid. Cholecystokinin was infused at a constant rate of 40 ng/kg per hour. Duodenal fluid was collected on ice for 80 minutes in four 20-minute aliquots. Aspirated fluid was analyzed for enzyme concentration with an automated chemistry analyzer in the hospital biochemistry laboratory. Nineteen healthy volunteers were studied. The mean volume (+/-SEM) of duodenal fluid collected was 85 +/- 4.4 mL (range, 48 to 118 mL). Fluid analysis revealed a significant rise in mean lipase concentration (+/-SEM) from a baseline of 595,680 +/- 11,930 IU/L to a peak of 1,778,847 +/- 171,204 IU/L (mean difference = 1,183,167 IU/L; 95% CI= 664,459 IU/L to 1,701,875 IU/L; < 0.001, Student test). Increases in amylase concentrations were markedly less pronounced and did not reach statistical significance. Mean peak lipase concentration occurred within 50 minutes of acinar cell stimulation. All patients tolerated tube placement, and there were no episodes of acute pancreatitis or abdominal pain. Pancreatic lipase concentrations in duodenal fluid increase nearly threefold after cholecystokinin stimulation in healthy volunteers. This magnitude of enzyme secretory response may be a marker of pancreatic function and could potentially lead to a more clinically useful and simpler pancreatic function test. This physiologic study serves as the basis for our further investigations of cholecystokinin-stimulated lipase concentrations as a new test in the assessment of pancreatic insufficiency.

EFFECT OF [formula omitted] -AMINOCARNITINE, AN INHIBITOR OF MITOCHONDRIAL FATTY ACID OXIDATION, ON THE EXOCRINE PANCREAS AND LIVER IN FASTED RATS

Fasting induces pancreatic secretory lipase, possibly through an increased utilization of fatty acids and/or ketone bodies by the acinar cells. To test this hypothesis, the effects of l -aminocarnitine (ACA), an inhibitor of mitochondrial β-oxidation and ketone body formation, on the pancreatic enzyme composition were studied in rats. The characteristics and reversibility of the hepatic steatosis produced by ACA in fasted animals were also investigated. In fasted rats, ACA decreased the plasma levels of β-hydroxybutyrate, glucose and insulin, but increased that of glucagon. Fasting for 3 days increased the pancreatic lipase content by 80%. Administration of ACA (3, 10 or 30 mg kg−1daily) for 3 days to fasted rats led to dose-related decreases in pancreatic lipase content, the fasting-induced increase was prevented even by the lowest dose. Nevertheless, ACA in the fasted rats likewise decreased the pancreatic contents of protein, amylase and trypsinogen to varying degrees, suggesting a general defect of protein synthesis. The 3-day treatment with ACA during fasting led to dose-related, marked increases in hepatic weight and triglyceride content. Light and electron microscopy revealed lipid vesicles of varying sizes in the hepatocytes; the fat deposition was predominant in the periportal zones of the hepatic lobules. By means of electron microscopy, lipid vacuoles were observed in the centroacinar cells, but not in the acinar cells of the pancreas. In rats treated with 30 mg kg−1of ACA daily for 3 days while they were fasted, cessation of ACA treatment and refeeding with normal chow led to normalization of the pancreatic enzyme contents within 6 days, and gradual and complete disappearance of the hepatic steatosis within 24 days. Microscopy also demonstrated complete recovery in both the liver and the pancreas. The results indicate that pancreatic secretory lipase induction during the adaptive phase of starvation is dependent on an unhindered mitochondrial β-oxidation of fatty acids and ketogenesis. The dose-related degree of hepatic triglyceride accumulation which can be produced readily by administration of ACA during short-term starvation in the rat may serve as a new, convenient experimental model for studies of fatty liver. 2000 Academic Press@p$hr

ONE-YEAR TREATMENT WITH CHOLECYSTOKININ-OCTAPEPTIDE AND SECRETIN: EFFECTS ON PANCREATIC TROPHISM IN THE RAT

The effects of long-term administration of cholecystokinin octapeptide (CCK-8) with or without secretin on the pancreas were examined in groups of rats treated with: (1) CCK-8 (1 μg kg−1); (2) secretin+CCK-8 (1 μg kg−1of each); or (3) saline, administered subcutaneously twice daily for 5 out of 7 days for 6 or 12 months. A number of rats from all groups were studied for: (1) pancreatic size and biochemical composition (n=6 for each group); (2) pancreatic secretion in the anesthetized state (n=5 for each group); and (3) pancreatic histology (n=6 for each group) after a 6-month treatment period. The rest of the animals treated for an additional 6-month period (n=13 for each group) were examined for pancreatic size and histology. CCK-8 increased the weight of the pancreas and its contents of DNA, protein, trypsinogen, chymotrypsinogen, proelastase, secretory trypsin inhibitor and amylase, but not that of lipase when given for 6 months, whereas administration of secretin+CCK-8 doubled the pancreatic content of lipase and increased all trophic parameters (except the amylase content) over those of CCK-8-treated rats. Maximum pancreatic volume and protein outputs in response to CCK-8 were higher in both of the hormone-treated groups than in the control; the sensitivity to the secretory action of CCK-8 was not altered. Pancreatic mass increased in response to either treatment after 12 months as well. Histological examination did not reveal pancreatic neoplasia in either group. The results indicate that long-term administration of CCK-8 or secretin+CCK-8 in rats results in sustained pancreatic hypertrophy and hyperplasia with secretory hyperfunction with no evidence of neoplastic alterations.

Effects of ethanol and protein deficiency on pancreatic digestive and lysosomal enzymes.

The pathogenesis of alcoholic pancreatitis is not fully understood. An increase in pancreatic digestive and lysosomal enzyme synthesis because of ethanol consumption could contribute to the development of pancreatic injury in alcoholics. This study aimed, firstly, to determine the effect of ethanol on the content and messenger RNA levels of pancreatic digestive enzymes and on the messenger RNA level of the lysosomal enzyme cathepsin B, and secondly, to examine the influence of concomitant protein deficiency (a known association of alcoholism and pancreatic injury) on these effects. A rat model of chronic ethanol administration was used in which rats were fed in groups of four, and for four weeks, protein sufficient and protein deficient diets with or without ethanol. Ethanol increased the pancreatic content of lipase but did not influence chymotrypsinogen or trypsinogen values. mRNA levels for lipase, trypsinogen, and chymotrypsinogen were raised in rats fed ethanol. Protein deficiency resulted in reduced tissue levels of lipase, chymotrypsinogen, and amylase but did not influence trypsinogen values. mRNA levels for proteases were increased in protein deficient rats, while those for lipase remained unaltered. Both ethanol and protein deficiency increased mRNA levels for cathepsin B. It is concluded that chronic ethanol consumption, in both protein sufficient and protein deficient states, increases the capacity of the pancreatic acinar cell to synthesise digestive and lysosomal enzymes.

Effect of the addition of pancreatic lipase on the ripening of dry-fermented sausages — Part 2. Free fatty acids, short-chain fatty acids, carbonyls and sensory quality

The effect of the addition of nine different amounts ( 3–500 units) of pancreatic lipase on the composition of free fatty acids (FFA), short-chain fatty acids and carbonyls, as well as the sensory quality, has been studied on dry fermented sausages. The lipase produced a greater release of all fatty acids in relation to the control sausages. The greater the pancreatic lipase content, the higher the release of these fatty acids, the most important ones being myristic, palmitoleic and oleic acids. A lower release of linoleic acid was observed, probably because of its oxidative degradation. At the end of the ripening in all lipase-added batches, a clear increase of the carbonyl content was noticed in relation to conventional sausages. No consistent changes were observed in the short-chain fatty acid fraction. In the sensory evaluation, the highest significant differences ( P < 0·01) between control sausages and lipase-added batches were observed when 60 and 90 lipase units were used. According to the chemical and sensory analyses, it can be concluded that the addition of 60 and 90 units to sausages seems to be useful to enhanced the flavour of these products.

Decrease in contents of pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase in rats with streptozotocin-induced diabetes.

The changes in contents of pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase in rats with streptozotocin (STZ)-induced diabetes have been studied. The contents of pancreatic carboxyl ester lipase and phospholipase A2 decreased by 40% and 45%, respectively, 5 days after injection of STZ, whereas pancreatic lipase steadily increased to 100% over control. The content of lingual lipase decreased sharply by more than 90% 2 days after STZ injection, followed by a tendency to recover slightly. Insulin treatment at a dose abolishing the urine glucose in diabetic rats for 3 days restored the contents of pancreatic lipase, carboxyl ester lipase, and lingual lipase but not pancreatic phospholipase A2. The results indicate that lack of insulin action induces an anticoordinate change in gastrointestinal lipolytic enzymes, with decreases in pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase contents and an increase in pancreatic lipase content.