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Medical Oncology (Northwood, London,... Apr 2022To evaluate omega-3 fatty acid-rich enteral nutrient effects in patients with unresectable or recurrent biliary tract or pancreatic cancers during chemotherapy. Enteric...
Effects of an enteral nutrient-rich therapy with omega-3 fatty acids in patients with unresectable or recurrent biliary tract cancer or pancreatic cancer during chemotherapy: a case-control study.
To evaluate omega-3 fatty acid-rich enteral nutrient effects in patients with unresectable or recurrent biliary tract or pancreatic cancers during chemotherapy. Enteric nutritional supplements containing omega-3 fatty acids (Racol) was administered to aforementioned patients with cancers during chemotherapy. The skeletal muscle mass and blood test data were obtained pre-administration and 28 and 56 days after. Patients with pancreatic cancer were administered the digestive enzyme supplement pancrelipase (LipaCreon) 28 days after the start of Racol administration. The number of chemotherapies skipped due to neutropenia was recorded for 2 months before and after enteral nutrient initiation. In all 39 patients, the skeletal muscle mass increased on day 56 versus baseline (median 17.3 kg vs. 14.8 kg, p < 0.01), number of chemotherapies skipped decreased (mean: 0.65 times/month vs. 1.3 times/month, p = 0.03), and retinol-binding protein (mean: 2.56 mg/dL vs. 2.42 mg/dL, p = 0.05) increased. Patients with pancreatic cancer showed increased blood eicosapentaenoic acid concentration on day 56 versus baseline (median: 48.1 μg/mL vs. 37.0 μg/mL, p = 0.04) and increased skeletal muscle mass (median 16.8 kg vs. 14.4 kg, p = 0.006). Baseline median neutrophil count increased significantly from 2200/μL at baseline to 2500/μL (p = 0.04). Patients with biliary tract cancer during chemotherapy also exhibited increased skeletal muscle mass following omega-3 supplementation (median 17.3 kg vs. 15.8 kg, p = 0.01). In patients undergoing chemotherapy for unresectable or post-recurrence pancreatic and biliary tract cancers, high-omega-3 fatty acid nutrition therapy use improved skeletal muscle maintenance and chemotherapy dosing intensity.
Topics: Biliary Tract Neoplasms; Case-Control Studies; Fatty Acids, Omega-3; Gastrointestinal Neoplasms; Humans; Nutrients; Pancreatic Neoplasms
PubMed: 35478069
DOI: 10.1007/s12032-021-01625-4 -
Internal Medicine (Tokyo, Japan) Jul 2022An 89-year-old woman underwent examinations for leg edema. Blood tests indicated low nutrition and low pancreatic enzymes, and a stool examination indicated fatty stool....
An 89-year-old woman underwent examinations for leg edema. Blood tests indicated low nutrition and low pancreatic enzymes, and a stool examination indicated fatty stool. Computed tomography showed pleural effusion, ascites, and cystic lesions in the pancreatic head and mural nodules within the cysts. Pancreatic juice cytology revealed adenocarcinoma. The diagnosis was pancreatic exocrine insufficiency caused by intraductal papillary mucinous carcinoma. The patient did not wish to undergo surgery. Therefore, diuretics, component nutrients, and pancreatic exocrine replacement therapy using pancrelipase were initiated. After starting treatment, her leg edema, pleural effusion, and ascites disappeared, and her activities of daily living improved markedly.
Topics: Activities of Daily Living; Adenocarcinoma, Mucinous; Adenocarcinoma, Papillary; Aged, 80 and over; Ascites; Carcinoma, Pancreatic Ductal; Edema; Exocrine Pancreatic Insufficiency; Female; Humans; Leg; Pancreatic Neoplasms; Pleural Effusion
PubMed: 34840231
DOI: 10.2169/internalmedicine.8611-21 -
Gastric Cancer : Official Journal of... May 2018Gastrectomy for gastric cancer is a significant cause of secondary exocrine pancreatic insufficiency. Pancreatic enzyme replacement therapy may influence nutritional... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Gastrectomy for gastric cancer is a significant cause of secondary exocrine pancreatic insufficiency. Pancreatic enzyme replacement therapy may influence nutritional status and quality of life after gastrectomy, but the pertinent clinical research to date remains controversial. A randomized controlled trial to test this hypothesis was carried out.
METHODS
After gastrectomy, 43 patients with gastric cancer were randomly assigned to a normal diet (Normal-d; n = 21) or to a pancreatic enzyme supplementation diet (PES-d; n = 22) and were followed up during a 12-month period, assessing nutritional status and quality of life through body mass index (BMI), instant nutritional assessment (INA) class status, serum pre-albumin (SPA) values, and GastroiIntestinal Quality of Life Index (GIQLI).
RESULTS
BMI was not significantly influenced by the type of diet; INA class status was significantly improved in the PES-d arm, particularly during the first 3 months after gastrectomy; SPA levels increased in both arms at 6 months after gastrectomy, reaching significantly higher values in the PES-d arm at 12 months. GIQLI was not significantly influenced by the type of diet throughout the follow-up period; however, this index significantly improved in the PES-d arm between the first and third month after gastrectomy.
CONCLUSIONS
PES-d improves nutritional status and quality of life after gastrectomy for gastric cancer, particularly within 3 months from the operation. A larger, multicenter trial is necessary to address the potential influence of several confounding variables such as disease stage and adjuvant treatments.
Topics: Adenocarcinoma; Aged; Exocrine Pancreatic Insufficiency; Female; Gastrectomy; Gastrointestinal Agents; Humans; Male; Middle Aged; Nutritional Status; Pancrelipase; Stomach Neoplasms
PubMed: 28804801
DOI: 10.1007/s10120-017-0757-y -
Endocrinology Sep 2014Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of glucose homeostasis and energy balance. However, the role of PTP1B in pancreatic endocrine...
Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of glucose homeostasis and energy balance. However, the role of PTP1B in pancreatic endocrine function remains largely unknown. To investigate the metabolic role of pancreatic PTP1B, we generated mice with pancreas PTP1B deletion (panc-PTP1B KO). Mice were fed regular chow or a high-fat diet, and metabolic parameters, insulin secretion and glucose tolerance were determined. On regular chow, panc-PTP1B KO and control mice exhibited comparable glucose tolerance whereas aged panc-PTP1B KO exhibited mild glucose intolerance. Furthermore, high-fat feeding promoted earlier impairment of glucose tolerance and attenuated glucose-stimulated insulin secretion in panc-PTP1B KO mice. The secretory defect in glucose-stimulated insulin secretion was recapitulated in primary islets ex vivo, suggesting that the effects were likely cell-autonomous. At the molecular level, PTP1B deficiency in vivo enhanced basal and glucose-stimulated tyrosyl phosphorylation of EphA5 in islets. Consistently, PTP1B overexpression in the glucose-responsive MIN6 β-cell line attenuated EphA5 tyrosyl phosphorylation, and substrate trapping identified EphA5 as a PTP1B substrate. In summary, these studies identify a novel role for PTP1B in pancreatic endocrine function.
Topics: Animals; Female; Gene Knockout Techniques; Glucose; Glucose Intolerance; Insulin; Insulin-Secreting Cells; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pancrelipase; Protein Tyrosine Phosphatase, Non-Receptor Type 1
PubMed: 24956127
DOI: 10.1210/en.2013-2004 -
The Journal of Biological Chemistry Feb 2011Although bovine pancreatic RNase is one of the best characterized proteins in respect to structure and in vitro refolding, little is known about its synthesis and...
Although bovine pancreatic RNase is one of the best characterized proteins in respect to structure and in vitro refolding, little is known about its synthesis and maturation in the endoplasmic reticulum (ER) of live cells. We expressed the RNase in live cells and analyzed its folding, quality control, and secretion using pulse-chase analysis and other cell biological techniques. In contrast to the slow in vitro refolding, the protein folded almost instantly after translation and translocation into the ER lumen (t(½) < 3 min). Despite high stability of the native protein, only about half of the RNase reached a secretion competent, monomeric form and was rapidly transported from the rough ER via the Golgi complex (t(½) = 16 min) to the extracellular space (t(½) = 35 min). The rest remained in the ER mainly in the form of dimers and was slowly degraded. The dimers were most likely formed by C-terminal domain swapping since mutation of Asn(113), a residue that stabilizes such dimers, to Ser increased the efficiency of secretion from 59 to 75%. Consistent with stringent ER quality control in vivo, the secreted RNase in the bovine pancreas was mainly monomeric, whereas the enzyme present in the cells also contained 20% dimers. These results suggest that the efficiency of secretion is not only determined by the stability of the native protein but by multiple factors including the stability of secretion-incompetent side products of folding. The presence of N-glycans had little effect on the folding and secretion process.
Topics: Animals; CHO Cells; Cattle; Cricetinae; Cricetulus; Endoplasmic Reticulum; Enzyme Stability; Pancrelipase; Protein Biosynthesis; Protein Folding; Protein Multimerization; Protein Transport; Ribonuclease, Pancreatic
PubMed: 21156800
DOI: 10.1074/jbc.M110.171694 -
Transplant International : Official... Sep 2021Static cold storage (SCS) is the standard method for pancreas preservation prior to transplantation; however, it does not permit organ assessment. Normothermic...
Static cold storage (SCS) is the standard method for pancreas preservation prior to transplantation; however, it does not permit organ assessment. Normothermic reperfusion (NR) is utilized clinically for other organs to assess viability. Our aim was to develop NR using normothermic machine perfusion technique to simulate reperfusion at the time of transplantation, enabling evaluation of oxygenated hypothermic machine perfusion (HMPO2) as a newer strategy to optimize pancreas preservation. 13 porcine pancreases procured after circulatory death were divided into 3 groups: 4 pancreases preserved using SCS, and 2 groups preserved by HMPO2 (n = 4 and n = 5, differing by type of preservation solution). Duration of perfusion or cold storage was 6 hours before the 1-hour assessment using NR. Outcome measures were perfusion characteristics, biochemistry and change in tissue water mass as oedema assessment. During NR, the HMPO2 groups demonstrated better perfusion characteristics, normal macroscopic appearances, decreased water mass and one HMPO2 group demonstrated a response to glucose stimulation. Conversely, the SCS group showed an increased water mass and developed early macroscopic appearances of oedema, interstitial haemorrhage and minimal portal outflow. This study suggests that ex situ assessment of pancreases by NR is promising, and that HMPO2 may be better than SCS.
Topics: Animals; Organ Preservation; Pancreas; Pancrelipase; Perfusion; Reperfusion; Swine
PubMed: 34448276
DOI: 10.1111/tri.13990 -
Antimicrobial Agents and Chemotherapy Jul 2017Tenofovir disoproxil fumarate (TDF), a prodrug of tenofovir, has oral bioavailability (25%) limited by intestinal transport (P-glycoprotein), and intestinal degradation...
Tenofovir disoproxil fumarate (TDF), a prodrug of tenofovir, has oral bioavailability (25%) limited by intestinal transport (P-glycoprotein), and intestinal degradation (carboxylesterase). However, the influence of luminal pancreatic enzymes is not fully understood. Physiologically based pharmacokinetic (PBPK) modeling has utility for estimating drug exposure from data. This study aimed to develop a PBPK model that included luminal enzyme activity to inform dose reduction strategies. TDF and tenofovir stability in porcine pancrelipase concentrations was assessed (0, 0.48, 4.8, 48, and 480 U/ml of lipase; 1 mM TDF; 37°C; 0 to 30 min). Samples were analyzed using mass spectrometry. TDF stability and permeation data allowed calculation of absorption rates within a human PBPK model to predict plasma exposure following 6 days of once-daily dosing with 300 mg of TDF. Regional absorption of drug was simulated across gut segments. TDF was degraded by pancrelipase (half-lives of 0.07 and 0.62 h using 480 and 48 U/ml, respectively). Previously reported maximum concentration (; 335 ng/ml), time to (; 2.4 h), area under the concentration-time curve from 0 to 24 h (AUC; 3,045 ng · h/ml), and concentration at 24 h (; 48.3 ng/ml) were all within a 0.5-fold difference from the simulated (238 ng/ml), (3 h), AUC (3,036 ng · h/ml), and (42.7 ng/ml). Simulated TDF absorption was higher in duodenum and jejunum than in ileum (p<0.05). These data support that TDF absorption is limited by the action of intestinal lipases. Our results suggest that bioavailability may be improved by protection of drug from intestinal transporters and enzymes, for example, by coadministration of enzyme-inhibiting agents or nanoformulation strategies.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Adolescent; Adult; Anti-HIV Agents; Carboxylesterase; HIV Infections; Humans; Lipase; Male; Middle Aged; Pancrelipase; Tenofovir; Young Adult
PubMed: 28416547
DOI: 10.1128/AAC.00105-17 -
Archives of Disease in Childhood Jul 1995Interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) concentrations were measured in faecal samples from nine patients with cystic fibrosis and nine healthy...
Interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) concentrations were measured in faecal samples from nine patients with cystic fibrosis and nine healthy age matched controls. The patients were assessed with Shwachman score, apparent energy absorption, pancreatic enzyme dosage, simple spirometry, and presence of pseudomonal colonisation. Median (range) wet stool IL-8 and TNF-alpha concentrations in patients were 32,113 pg/g (21,656-178,128) and 3187 pg/g (368-17,611) respectively, compared with < 43.5 pg (IL-8)/g (< 22-4079) and 99 pg (TNF-alpha)/g (< 0.26-231) in controls. IL-8 concentration was negatively correlated with Shwachman score (r = -0.79) and pancreatic enzyme dosage (r = -0.77), but not with energy absorption. Seven patients were mature enough to cooperate with spirometry. Their IL-8 concentrations correlated with percentage predicted forced expiratory volume in one second (r = -0.78). IL-8 concentration was greater in four patients with, than five without, established pseudomonal colonisation: median difference 134,583 pg/g. TNF-alpha concentration was not correlated with measures of disease severity. Faecal IL-8 concentration might reflect the severity of pulmonary inflammation in cystic fibrosis and could provide an easily obtainable marker of disease activity.
Topics: Adolescent; Adult; Biomarkers; Child; Cystic Fibrosis; Feces; Humans; Interleukin-8; Lipase; Lung; Pancreatic Extracts; Pancrelipase; Pseudomonas Infections; Spirometry; Tumor Necrosis Factor-alpha
PubMed: 7639556
DOI: 10.1136/adc.73.1.74 -
Molecules (Basel, Switzerland) Sep 2019A novel lipid inhibition peptide Leu-Leu-Val-Val-Try-Pro-Trp-Thr-Gln-Arg (PP1) (MW 1274.53 Da) was obtained from using enzymatic hydrolysis, gel filtration...
A novel lipid inhibition peptide Leu-Leu-Val-Val-Try-Pro-Trp-Thr-Gln-Arg (PP1) (MW 1274.53 Da) was obtained from using enzymatic hydrolysis, gel filtration chromatography, and LC-MS/MS. Its lipid inhibition effects indicated that the synthetic peptide PP1 exhibits a good inhibitory effect against porcine pancreatic lipase (PL) (47.95%) at 200 μg/mL, which could be attributed to its hydrogen binding into catalytic sites of PL (Ser153, Asp177, and His 264) by docking analysis. Furthermore, in 3T3-L1 cells, the synthetic PP1 remarkedly decreased the accumulation of intracellular triacylglycerol (27.9%, 600 μg/mL), which carried a similar consequence as the positive drug simvastatin (24.1%, 10 μM). Western blot revealed that PP1 inhibited the lipid accumulation and fatty acid synthesis in 3T3-L1 adipocytes in two pathways, primarily: nonalcoholic fatty liver disease (NAFLD) pathway (C/EBPα, SREBP-1c, AMPKα) and AMPK signaling pathway (SREBP-1c, PPARγ, AMPKα). In short, these results support that PP1 can be used as a potential agent against obesity.
Topics: 3T3-L1 Cells; Amino Acid Sequence; Animals; Chemical Fractionation; Chlorella; Dose-Response Relationship, Drug; Hydrolysis; Mice; Models, Molecular; Molecular Weight; Oligopeptides; Pancrelipase; Plant Extracts; Protein Conformation; Swine
PubMed: 31569521
DOI: 10.3390/molecules24193527 -
European Review For Medical and... Dec 2013Short bowel syndrome is a disabling disease requiring long-term nutritional support and ancillary drugs. Aiming to analyze the most commonly prescribed drugs, a... (Observational Study)
Observational Study
BACKGROUND
Short bowel syndrome is a disabling disease requiring long-term nutritional support and ancillary drugs. Aiming to analyze the most commonly prescribed drugs, a retrospective analysis was conducted is an outpatient cohort.
PATIENTS AND METHODS
Stable patients (N= 37, 59.5% males, age 51.1 ± 20.1 years, body mass index 20.1 ± 7.9 kg/m2) with three or more appointments in the Outpatient Service during the last 18 months were retrospectively analyzed. regarding oral pharmacologic prescriptions. Medications were classified as on label or off label.
RESULTS
A total of 257 oral prescriptions were retrieved from computer files, encompassing 17 different preparations. The majority was employed on label however 28.8% (74/257) were classified as off label and scrutinized with regard to indications. The main categories were pharmacologic modulators of gastrointestinal secretions and motility, along with antibiotics. Virtually all patients required one or more of such drugs, without differences regarding demographic or clinical variables. Adverse effects or premature drug discontinuation were not observed.
CONCLUSIONS
This is the first study to our knowledge highlighting the importance of adjuvant drugs, particularly with unconventional indications, in the management of short bowel syndrome. Antidiarrheic agents, pancrelipase micropellets, antacids and antibiotics represented the most relevant off label prescriptions for this population.
Topics: Administration, Oral; Adult; Aged; Ambulatory Care; Chi-Square Distribution; Drug Utilization Review; Female; Gastrointestinal Agents; Humans; Linear Models; Male; Middle Aged; Off-Label Use; Retrospective Studies; Short Bowel Syndrome; Treatment Outcome; Young Adult
PubMed: 24379057
DOI: No ID Found