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Journal of the Science of Food and... May 2018This study investigates a novel hydrogel synthesis method and its bio-release property. This hydrogel, with a three-dimensional network structure based on Auricularia...
BACKGROUND
This study investigates a novel hydrogel synthesis method and its bio-release property. This hydrogel, with a three-dimensional network structure based on Auricularia polytricha β-glucan, was characterised by means of Fourier transform infrared spectroscopy, H NMR and scanning electron microscopy. Vitamin B (VB , cobalamin) as a hydrophilic functional food component was entrapped into these hydrogels. The in vitro release profile of VB was established in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF).
RESULTS
The results showed that the hydrogel had medium pore size from 30 to 300 µm, and the swelling ratio increased with the degree of substitution. The hydrogel demonstrated good stability in SGF and bio-release capability in SIF for VB . The accumulated release rate is about 80% in SIF and below 20% in SGF, which indicated the significant different release property in stomach and intestine.
CONCLUSION
The Auricularia polytricha β-glucan-based hydrogel has a good swelling ratio, pepsin stability and pancrelipase-catalysed biodegradation property. The bio-release rate is significantly different in SIF and SGF, which indicated that this hydrogel could be a good intestinal target carrier of VB . © 2017 Society of Chemical Industry.
Topics: Basidiomycota; Drug Carriers; Drug Delivery Systems; Hydrogel, Polyethylene Glycol Dimethacrylate; Kinetics; Plant Extracts; Spectroscopy, Fourier Transform Infrared; Vitamin B 12; beta-Glucans
PubMed: 29064580
DOI: 10.1002/jsfa.8754 -
The Medical Letter on Drugs and... Oct 2017
Topics: Administration, Oral; Enzyme Replacement Therapy; Exocrine Pancreatic Insufficiency; Humans; Pancrelipase; Treatment Outcome
PubMed: 28977808
DOI: No ID Found -
Toxicology Letters Oct 2017The hypothesis of fetal origins indicates that exposures in early development could induce epigenetic modifications in the male germ-line, affecting the susceptibility...
The hypothesis of fetal origins indicates that exposures in early development could induce epigenetic modifications in the male germ-line, affecting the susceptibility of adult-onset disease for generations. p,p'-DDE, the primary metabolite of persistent organochlorine pesticide DDT, is highly correlated with impaired glucose tolerance (IGT) and a strong contributing factor to type 2 diabetes. In our previous study, ancestral p,p'-DDE exposure could induce transgenerational impaired male fertility with sperm Igf2 hypomethylation. It is still unknown whether this germline epigenetic defect would affect the somatic tissue endocrine pancreas. Gestating F0 generation females were exposed to p,p'-DDE from gestation day 8 to 15. The F1 male offspring were mated with female to produce F2 progeny. F3 generation was obtained by intercrossing the control and treated male and female of F2 generation and divided as C♂-C♀, DDE♂-DDE♀, DDE♂-C♀ and C♂-DDE♀. Results indicated that F1 offspring in p,p'-DDE group exhibited impaired glucose tolerance (IGT), abnormal insulin secretion, β-cell dysfunction and altered Igf2 and H19 expression induced by Igf2/H19 hypomethylation, which could be transferred to the F3 offspring through the male germ line. IGT and abnormal insulin secretion were more obvious in males than those in females. Ancestral p,p'-DDE exposure could induce transgenerational pancreatic impairment with Igf2/H19 epigenetic defect.
Topics: Animals; Diabetes Mellitus; Environmental Exposure; Epigenesis, Genetic; Ethyl Ethers; Female; Gene Expression Regulation; Glucose Tolerance Test; Insulin-Like Growth Factor II; Insulin-Secreting Cells; Male; Pancrelipase; RNA, Long Noncoding; RNA, Messenger; Rats; Rats, Sprague-Dawley
PubMed: 28867213
DOI: 10.1016/j.toxlet.2017.08.083 -
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 -
International Medical Case Reports... 2017Cystic fibrosis (CF) is a disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator protein in the epithelial membrane, and affects at...
Cystic fibrosis (CF) is a disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator protein in the epithelial membrane, and affects at least 30,000 people in the USA. There are between 900 and 1000 new cases diagnosed every year. Traditionally, CF has been treated symptomatically with pancreatic enzymes, bronchodilators, hypertonic saline, and pulmozyme. In July 2015, the US Food and Drug Administration approved Orkambi (lumacaftor/ivacaftor), a combination drug that works on reversing the effects of the defective cystic fibrosis transmembrane conductance regulator protein. Orkambi and mucolytics decrease the viscosity of mucous secretions, leading to an accumulation of hypoviscous fluid in the alveoli, resulting in dyspnea. This presentation can be mistaken for an infective exacerbation. We present a case in which a young female with CF recently started on Orkambi therapy presented to her primary care physician with dyspnea and increased respiratory secretions and was admitted to the hospital for 2 weeks of intravenous and inhaled antibiotic therapy for a presumed CF exacerbation. We highlight this case to bring awareness and educate patients and clinicians of the side-effect profile of Orkambi therapy with an intent to avoid unnecessary hospitalizations, inpatient antibiotics, and other costly medical services.
PubMed: 28769592
DOI: 10.2147/IMCRJ.S139022 -
HPB : the Official Journal of the... Oct 2017Although many patients undergoing pancreatoduodenectomy (PD) for cancer have pancreatic exocrine insufficiency, pancreatic enzyme replacement therapy (PERT) is not... (Observational Study)
Observational Study
BACKGROUND
Although many patients undergoing pancreatoduodenectomy (PD) for cancer have pancreatic exocrine insufficiency, pancreatic enzyme replacement therapy (PERT) is not routinely used, and effects upon post-operative survival are unclear.
METHODS
This review of patients undergoing PD for periampullary malignancy sought to test for an association between PERT and overall survival, with post-hoc subgroup analysis performed after stratifying patients by the year of surgery, pancreatic duct width and tumour type.
RESULTS
Some 202/469 (43.1%) patients received PERT. After accounting for pathological variables and chemotherapy, PERT use was found to be independently associated with improved survival on multivariable analysis [HR 0.72 (95% CI: 0.52-0.99), p = 0.044] and on propensity matched analysis (p = 0.009). The effect of PERT upon improved survival was predominantly observed amongst patients with a dilated pancreatic duct (≥3 mm).
DISCUSSION
PERT use was independently associated with improved survival following PD for cancer. The validity of this observation is supported by an effect largely confined to those patients with a dilated pancreatic duct. The nutritional status of patients undergoing PD for cancer needs further investigation and the effects of PERT require verification in further clinical studies.
Topics: Aged; Bile Duct Neoplasms; Disease Progression; Disease-Free Survival; Duodenal Neoplasms; Enzyme Replacement Therapy; Exocrine Pancreatic Insufficiency; Female; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pancrelipase; Propensity Score; Proportional Hazards Models; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome
PubMed: 28711377
DOI: 10.1016/j.hpb.2017.05.009 -
Molecular Biology of the Cell Sep 2017Stress responses are highly nuanced and variable, but how this diversity is achieved by modulating receptor function is largely unknown. Corticotropin-releasing factor...
Stress responses are highly nuanced and variable, but how this diversity is achieved by modulating receptor function is largely unknown. Corticotropin-releasing factor receptors (CRFRs), class B G protein-coupled receptors, are pivotal in mediating stress responses. Here we show that the two known CRFRs interact to form heteromeric complexes in HEK293 cells coexpressing both CRFRs and in vivo in mouse pancreas. Coimmunoprecipitation and mass spectrometry confirmed the presence of both CRFR and CRFβR, along with actin in these heteromeric complexes. Inhibition of actin filament polymerization prevented the transport of CRFβR to the cell surface but had no effect on CRFR. Transport of CRFR when coexpressed with CRFR became actin dependent. Simultaneous stimulation of cells coexpressing CRFR+CRFβR with their respective high-affinity agonists, CRF+urocortin2, resulted in approximately twofold increases in peak Ca responses, whereas stimulation with urocortin1 that binds both receptors with 10-fold higher affinity did not. The ability of CRFRs to form heteromeric complexes in association with regulatory proteins is one mechanism to achieve diverse and nuanced function.
Topics: Actin Cytoskeleton; Animals; Cell Membrane; Corticotropin-Releasing Hormone; HEK293 Cells; Humans; Mice; Pancrelipase; Receptors, Corticotropin-Releasing Hormone; Signal Transduction; Stress, Physiological; Tissue Culture Techniques
PubMed: 28701349
DOI: 10.1091/mbc.E16-11-0778 -
Annals of Surgery Oct 2017Our aim was to assess quality of life (QOL) and functionality in a large cohort of patients ≥5-years after pancreaticoduodenectomy (PD).
OBJECTIVE
Our aim was to assess quality of life (QOL) and functionality in a large cohort of patients ≥5-years after pancreaticoduodenectomy (PD).
BACKGROUND
Long-term QOL outcomes after PD for benign or malignant disease are largely undocumented.
METHODS
We administered the EORTC QLQ-C30 questionnaire to patients who underwent PD for neoplasms from 1998 to 2011 and compared their scores with an age- and sex-matched normal population. Clinical relevance (CR) of differences was scored as small (5-10), moderate (10-20), or large (>20) based on validated interpretation of clinically important differences.
RESULTS
Of 305 PD survivors, 245 (80.3%) responded, of whom 157 (64.1%) underwent PD for nonmalignant lesions. Median follow-up was 9.1 years (range 5.1 -21.2 yrs). New-onset diabetes developed in 10.6%; 50.4% reported taking pancreatic enzymes; 54.6% reported needing antacids. Compared with the age- and sex-adjusted controls, PD survivors demonstrated higher global QOL (78.7 vs 69.7, CR small, P < 0.001), physical (86.7 vs 77.9, CR small, P < 0.001) and role-functioning scores (86.3 vs 74.1, CR medium, P < 0.001). Using linear regression and adjusting for socioeconomic variables, there were no differences in QOL or functional scores in the benign versus malignant subgroups. Older age at operation was associated with worse physical-functioning (-0.4/yr, P = 0.008). Taking pancrelipase (-6.8, P = 0.035) or antacids (-6.3, P = 0.044) were both associated with lower social-functioning scores.
CONCLUSIONS
Patients who had a PD demonstrated better global QOL, physical- and role-functioning scores at 5-years when compared with age- and sex-matched controls. Approximately half of the patients required pancreatic enzyme replacement, while only 11% developed new-onset diabetes.
Topics: Adult; Aged; Aged, 80 and over; Antacids; Enzyme Replacement Therapy; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pancreatic Diseases; Pancreatic Neoplasms; Pancreaticoduodenectomy; Psychometrics; Quality of Life; Socioeconomic Factors; Survivors
PubMed: 28657944
DOI: 10.1097/SLA.0000000000002380 -
Chemical Biology & Drug Design Dec 2017Fluoroquinolones (FQs) have been identified recently as potent inhibitors of pancreatic lipase (PL). The aim of this study was to synthesize novel FQs and...
Fluoroquinolones (FQs) have been identified recently as potent inhibitors of pancreatic lipase (PL). The aim of this study was to synthesize novel FQs and triazolofluoroquinolones (TFQs) and to evaluate them in vitro with respect to their antilipolytic efficacy and potency properties. The PL-IC values of 12 FQs and TFQs (3 (a-c)-6 (a-c)) were in the range of 12.5-189.1 μm. These values are further supported by docking studies. The suggested association between obesity and colorectal cancer initiated the evaluation of antiproliferative activity of the new FQs and TFQs against a panel of obesity-related colorectal cells (HT29, HCT116, SW620 CACO2, and SW480). Sulforodamine B colorimetric assay revealed that some derivatives exhibited unselective cytotoxicity against HT29, HCT116, SW620 CACO2, and SW480. Remarkably, FQ 4a's selective cytotoxicity against HCT116 was found valuable with IC value of 4.2 μm which exceeds that of cisplatin with a substantial selective cytotoxicity in periodontal ligament fibroblasts. In conclusion, FQ and TFQ derivatives may unveil new antiobesity and anticancer agents in the future.
Topics: Antineoplastic Agents; Binding Sites; Caco-2 Cells; Catalytic Domain; Cell Line, Tumor; Cell Survival; Fluoroquinolones; Humans; Hydrogen Bonding; Inhibitory Concentration 50; Molecular Docking Simulation; Pancrelipase; Structure-Activity Relationship; Thermodynamics
PubMed: 28639358
DOI: 10.1111/cbdd.13049 -
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