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BMC Cancer Oct 2019Patients with metastatic renal carcinoma frequently have pre-existing renal impairment and not infrequently develop worsening renal function as a complication of their...
BACKGROUND
Patients with metastatic renal carcinoma frequently have pre-existing renal impairment and not infrequently develop worsening renal function as a complication of their treatment. The presence of pancreatic metastases in patients with metastatic renal carcinoma, often confers a more favourable prognosis and as a consequence this patient group may be exposed to such treatments for more prolonged periods of time. However, the development of renal failure may also be a consequence of the cancer itself rather than its treatment.
CASE PRESENTATION
We present an 84-year-old patient receiving the tyrosine kinase inhibitor (TKI) pazopanib for metastatic renal carcinoma who developed oxalate nephropathy as a consequence of pancreatic exocrine insufficiency resulting from pancreatic metastases.
CONCLUSIONS
This case demonstrates the importance of investigating unexpected toxicities and highlights the potential consequences of pancreatic insufficiency and its sequelae in patients with pancreatic metastases.
Topics: Acetates; Aged, 80 and over; Calcium Compounds; Carcinoma, Renal Cell; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Humans; Indazoles; Kidney Failure, Chronic; Kidney Neoplasms; Male; Oxalates; Pancreatic Neoplasms; Pancrelipase; Protein Kinase Inhibitors; Pyrimidines; Renal Dialysis; Sulfonamides; Treatment Outcome
PubMed: 31623580
DOI: 10.1186/s12885-019-6215-y -
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 -
Haemophilia : the Official Journal of... Nov 2019
Review
Topics: Factor VIII; Hematologic Diseases; Hemophilia A; Humans; Infant; Male; Pancrelipase; Shwachman-Diamond Syndrome
PubMed: 31523886
DOI: 10.1111/hae.13849 -
Asian Pacific Journal of Cancer... Aug 2019Paramount efforts by pharmaceutical industry to identify new targets for obesity-diabetes (Diabesity) pharmacological intervention have led to a number of agents...
Paramount efforts by pharmaceutical industry to identify new targets for obesity-diabetes (Diabesity) pharmacological intervention have led to a number of agents developed and directed at DPP IV [dipeptidyl peptidase IV] enzyme inhibition thereby enhancing endogenous insulinotropic incretins. Besides antioxidative-antiinflammtory molecules that inhibit accumulation of advanced glycation end products (AGEs) can be good candidates for ameliorating diabetic complications. Fluoroquinolones (FQs) have been identified recently as potent inhibitors of pancreatic lipase (PL). 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). The aim of the current study is to examine the potential of newly synthesized FQs and triazolofluoroquinolones (TFQs) derivatives as dual inhibitors for glycation and inflammation, DPP IV inhibitors, PL inhibitors for dual management of obesity and diabetes, as well as antiprolifertaive efficacy against colorectal cancer cell lines. Sulforodamine B (SRB) colorimetric assay revealed that some derivatives exhibited unselective cytotoxity against HT29, HCT116, SW620 CACO2 and SW480. The superior antiglycation activity of the reduced derivatives 4a and 4b over that of aminoguanidine with respective IC50 (μM) values of 3.05±0.33 and 8.51±3.21; none of the tested synthetic compounds could perform equally effectively to Diprotin A, a dose dependent inhibitor of DPP IV. Compounds 4a, 5a, 3b, 4b and 5b demonstrated anti-inflammatory IC50 values exceeding that of indomethacin. Compounds 3a and 4a showed IC50 lower than 10 μM as PL inhibitors. In conclusion, FQ and TFQ derivatives may unveil new antiobesity and anticancer agents in the future. Our research qualifies FQs and TFQs as promising candidates for the development of related α-dicarbonyl scavengers as therapeutic agents to protect cells against carbonyl stress.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Binding Sites; Cell Proliferation; Cells, Cultured; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Enzyme Inhibitors; Fluoroquinolones; Glycosylation; Inflammation; Inhibitory Concentration 50; Macrophages; Mice; Molecular Docking Simulation; Pancrelipase
PubMed: 31450926
DOI: 10.31557/APJCP.2019.20.8.2503 -
The prevalence and impact of low faecal elastase-1 in community-based patients with type 2 diabetes.Diabetes Research and Clinical Practice Oct 2019To determine the prevalence of low faecal elastase-1 (FE-1) (≤200 μg/g) in type 2 diabetes (T2DM), and to test the hypothesis that pancreatic enzyme replacement...
AIMS
To determine the prevalence of low faecal elastase-1 (FE-1) (≤200 μg/g) in type 2 diabetes (T2DM), and to test the hypothesis that pancreatic enzyme replacement therapy (PERT) would reduce postprandial glycaemia after a high-fat, high-carbohydrate meal in T2DM subjects with low FE-1.
METHODS
Of 109 community-based patients who submitted stool samples, 10 had low FE-1 and 8 were recruited (6 male, 2 female, 67.8 ± 3.0 years). Participants were given a high-fat, high-carbohydrate meal (718 kcal) with either pancrelipase (50,000 units) or placebo in a randomised, double-blind, crossover fashion. The primary outcome was the difference in postprandial glycaemia following PERT vs placebo, as evaluated by the incremental area under the postprandial plasma glucose curve (iAUC). Secondary outcomes included differences in gastric half-emptying time (T50) measured using scintigraphy, and C-peptide iAUC.
RESULTS
The prevalence of low FE-1 in T2DM was 9.2% (95% CI 3.8-14.6%). There was no difference in postprandial glycaemia iAUC (P = 0.38), gastric emptying T50 (P = 0.69) or C-peptide iAUC (P = 0.25) after PERT compared to placebo.
CONCLUSIONS
Decreased FE-1 has a relatively low prevalence in community-based patients with T2DM, and PERT does not reduce postprandial glycaemia in these patients.
CLINICAL TRIAL REGISTRATION NUMBER
ACTRN12617000349347.
Topics: Aged; Diabetes Mellitus, Type 2; Feces; Female; Humans; Male; Pancreatic Elastase; Prevalence
PubMed: 31446113
DOI: 10.1016/j.diabres.2019.107822 -
Pancreas Sep 2019Reliable pancreatic function tests in patients with chronic pancreatitis (CP) are needed. This cohort study identified malabsorption in people with CP compared with...
Pancreatic Function in Chronic Pancreatitis: A Cohort Study Comparing 3 Methods of Detecting Fat Malabsorption and the Impact of Short-term Pancreatic Enzyme Replacement Therapy.
OBJECTIVES
Reliable pancreatic function tests in patients with chronic pancreatitis (CP) are needed. This cohort study identified malabsorption in people with CP compared with healthy people and then investigated short-term pancreatic enzyme replacement therapy (PERT) and fat malabsorption, nutritional status, and quality of life (QOL).
METHODS
Subjects with CP were evaluated before and after PERT and compared with the healthy cohort using coefficient of fat absorption (CFA), stool bomb calorimetry, and the malabsorption blood test (MBT). Anthropometrics, micronutrients, and QOL data were collected. Group means at baseline and after PERT were analyzed.
RESULTS
The 24 subjects with CP had greater stool energy loss (5668 cal/g [standard deviation {SD}, 753] vs 5152 cal/g [SD, 418], P < 0.01), reduced triglyceride absorption (MBT, 8.3 mg·h/dL [SD, 4.3] vs 17.7 mg·h/dL [SD, 10.3], P < 0.001), lower fat intake, and poorer QOL. Differences in CFA were not significant (90.9% [SD, 12.8] vs 95.4% [SD, 9.3]). After PERT, triglyceride absorption (Δ = 1.7 [SD, 3], P < 0.05) and QOL increased.
CONCLUSIONS
The MBT detected changes in triglyceride absorption in the absence of CFA changes. The MBT may be helpful in guiding PERT initiation in patients with CP before significant morbidity.
Topics: Adult; Cohort Studies; Enzyme Replacement Therapy; Exocrine Pancreatic Insufficiency; Fats; Female; Humans; Malabsorption Syndromes; Male; Middle Aged; Nutritional Status; Outcome Assessment, Health Care; Pancreas; Pancreatic Function Tests; Pancreatitis, Chronic; Pancrelipase; Quality of Life; Triglycerides
PubMed: 31404029
DOI: 10.1097/MPA.0000000000001381 -
Gastroenterology Jan 2020
Topics: Aged, 80 and over; Calcinosis; Diarrhea; Humans; Mauritius; Pancreas; Pancreatitis, Chronic; Pancrelipase; Tomography, X-Ray Computed; Weight Loss
PubMed: 31376389
DOI: 10.1053/j.gastro.2019.07.043 -
BMC Gastroenterology Jul 2019Cystic fibrosis (CF) is a genetic disorder of the epithelial CFTR apical chloride channel resulting in multi-organ manifestations, including pancreatic exocrine...
BACKGROUND
Cystic fibrosis (CF) is a genetic disorder of the epithelial CFTR apical chloride channel resulting in multi-organ manifestations, including pancreatic exocrine secretion. In the pancreas, CFTR abnormality results in abnormally viscous secretions that obstruct proximal ducts leading to fibrotic injury and ultimately pancreatic insufficiency in 85% of the CF population. CFTR modulators, including the potentiator ivacaftor, augment channel gating to restore 30-50% of CFTR-mediated anion transport. While CFTR modulation has been shown to alkalinize the pH of the alimentary tract and potentially augment pancreatic enzyme activity, the effect of ivacaftor on recurrent pancreatitis is emerging. Here we describe a case of a patient with CF (R117H/7 T/F508del) who presented with recurrent pancreatitis who was effectively treated with ivacaftor in the absence of respiratory symptoms.
CASE PRESENTATION
A 24-year-old white male with past medical history of recurrent acute pancreatitis presented for evaluation following a referral from an outside hospital. The patient reported a lifetime of gastrointestinal symptoms requiring over 20 hospitalizations for pancreatitis in the last 10 years. Prior U/S and CT imaging for pancreatitis ruled out gallstones or anatomical etiologies. Family history included a brother with CF carrier status who suffered from recurrent acute pancreatitis. Sweat chloride testing was suggestive of CFTR dysfunction (57 mmol/L). Genetic testing demonstrated disease causing CFTR mutations: R1117H/7 T/F508del. Patient was prescribed pancrelipase, however, he reported worsened gas and diarrhea symptoms. Pancrelipase was discontinued and the patient was prescribed ivacaftor 150 mg BID. After 6 weeks of ivacaftor treatment, patient reported improved gastrointestinal symptoms. For an additional 19 months, patient reported no episodes of pancreatitis until he discontinued ivacaftor. Over the next 3 weeks, patient experienced progressive nausea and sharp epigastric pain and laboratory studies confirmed pancreatitis. Patient was subsequently lost to follow up.
CONCLUSIONS
These findings support a possible relationship between the use of CFTR modulators, such as ivacaftor, in the management of recurrent pancreatitis in the setting of patients with cystic fibrosis and a CFTR mutation with residual CFTR activity or otherwise known to be responsive in vitro. Ivacaftor may be useful for recurrent pancreatitis, even in the absence of respiratory morbidity.
Topics: Aminophenols; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Male; Pancreatitis, Chronic; Quinolones; Recurrence; Treatment Outcome; Young Adult
PubMed: 31296159
DOI: 10.1186/s12876-019-1044-7 -
Pancreas Jul 2019Pancreatic cancer (PC) and its treatments can result in pancreatic exocrine insufficiency that requires pancreatic enzyme replacement therapy (PERT). Appropriate PERT...
OBJECTIVES
Pancreatic cancer (PC) and its treatments can result in pancreatic exocrine insufficiency that requires pancreatic enzyme replacement therapy (PERT). Appropriate PERT usage is during meals and snacks. The aim was to determine the frequency of appropriate use of PERT and its impact on symptom alleviation in PC through a patient-reported outcomes online platform.
METHODS
Users in the Pancreatic Cancer Action Network's Patient Registry were prompted to answer a standalone questionnaire about their experience with PERT.
RESULTS
Two hundred sixty-two users completed the PERT questionnaire (January 2016-January 2018). Patients who reported taking PERT with meals had higher alleviation of symptoms compared with those taking PERT prior to or after meals. Specifically, "feeling of indigestion," "light-colored or orange stools," and "visible food particles in stool" were significantly decreased. Patients taking PERT with meals reported weight gain and less weight loss.
CONCLUSIONS
Of the 89% of PC patients prescribed PERT, 65% were prescribed PERT appropriately with all meals and snacks. Overall compliance with PERT administration guidelines was low (50% [105/208]). Improvement in symptoms significantly correlated with appropriate use of PERT. Increase in PC patient and provider education about appropriate PERT usage and administration is warranted.
Topics: Adult; Aged; Aged, 80 and over; Enzyme Replacement Therapy; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Pancrelipase; Retrospective Studies; Surveys and Questionnaires; Treatment Outcome; Young Adult
PubMed: 31210656
DOI: 10.1097/MPA.0000000000001330 -
Chemistry (Weinheim An Der Bergstrasse,... Aug 2019A new protocol based on lipase-catalyzed tandem reaction toward α,β-enones/enoesters is presented. For the synthesis of the desired products the tandem process based...
A new protocol based on lipase-catalyzed tandem reaction toward α,β-enones/enoesters is presented. For the synthesis of the desired products the tandem process based on enzyme-catalyzed hydrolysis and Knoevenagel reaction starting from enol acetates and aldehyde is developed. The relevant impact of the reaction conditions including organic solvent, enzyme type, and temperature on the course of the reaction was revealed. It was shown that controllable release of the active methylene compound from the corresponding enol carboxylate ensured by enzymatic reaction diminishes significantly the formation of the unwanted co-products. Furthermore, this protocol was extended by including a second tandem chemoenzymatic transformation engaging various aldehyde precursors. After a careful optimization of the reaction conditions, the target products were obtained with yields up to 86 % and with excellent E/Z-selectivity.
Topics: Aldehydes; Animals; Biocatalysis; Hydrolysis; Lipase; Pancrelipase; Pentanones; Stereoisomerism; Swine
PubMed: 31136019
DOI: 10.1002/chem.201901491