A new method for determining endocrine disrupter compounds (EDCs) in sewage sludge is described in this paper. EDCs studied were bisphenol A (BPA) and alkylphenols (APs). In order to obtain a fast ...and simple method, selective pressurised liquid extraction (SPLE) and focused ultrasound solid–liquid extraction (FUSLE) were tested. Best results for SPLE were obtained using Florisil as clean‐up sorbent and dichloromethane as extraction solvent, while temperature was the only significant variable. Analyte extraction by SPLE was completed in only one extraction cycle of 1 min at 130°C. FUSLE was carried out in one step of 20 s at 75% power (0.5 cycles) and with 8 mL of ethyl acetate. Although the optimised FUSLE process was faster, simpler and cheaper, SPLE provided higher recovery values (ranging from 81 to 105%) and therefore SPLE‐based method was selected and validated. The SPLE and GC‐MS method showed an LOD of 10.7 ng/g for BPA and LODs between 1.2 and 41.6 ng/g for APs. Relative standard deviation values lower than 6% were obtained for all analytes. As a result, an efficient, fast and simple method based on SPLE and GC‐MS for the determination of BPA and APs in sewage sludge is proposed.
Summary
Background and Aims
Data on the outcomes after switching from adalimumab (ADA) originator to ADA biosimilar are limited. The aim was to compare the treatment persistence, clinical efficacy, ...and safety outcomes in inflammatory bowel disease patients who maintained ADA originator vs. those who switched to ADA biosimilar.
Methods
Patients receiving ADA originator who were in clinical remission at standard dose of ADA originator were included. Patients who maintained ADA originator formed the non‐switch cohort (NSC), and those who switched to different ADA biosimilars constituted the switch cohort (SC). Clinical remission was defined as a Harvey–Bradshaw index ≤4 in Crohn's disease and a partial Mayo score ≤2 in ulcerative colitis. To control possible confounding effects on treatment discontinuation, an inverse probability treatment weighted proportional hazard Cox regression was performed.
Results
Five hundred and twenty‐four patients were included: 211 in the SC and 313 in the NSC. The median follow‐up was 13 months in the SC and 24 months in the NSC (p < 0.001). The incidence rate of ADA discontinuation was 8% and 7% per patient‐year in the SC and in the NSC, respectively (p > 0.05). In the multivariate analysis, switching from ADA originator to ADA biosimilar was not associated with therapy discontinuation. The incidence rate of relapse was 8% per patient‐year in the SC and 6% per patient‐year in the NSC (p > 0.05). Six percent of the patients had adverse events in the SC vs. 5% in the NSC (p > 0.05).
Conclusion
Switching to ADA biosimilar did not impair patients' outcomes in comparison with maintaining on the originator.
Hepatic hematoma after ERCP: two new case reports Del Moral Martínez, María; Delgado Maroto, Ana; Cervilla Sáez de Tejada, María Eloísa ...
Revista española de enfermedades digestivas,
06/2017, Letnik:
109, Številka:
6
Journal Article
Recenzirano
Odprti dostop
ERCP is an endoscopic procedure with a complication risk ranging from 2.5 to 8%. The most frequent complications are pancreatitis, cholangitis, hemorrhage or perforation. Hepatic hematoma after ERCP ...is a potentially serious, rare complication. Not many cases are reported in the literature. We present here two new cases of hepatic hematoma following ERCP along with a review of the literature and possible therapeutic options.
the guidewire (GW) may enter the pancreatic duct during common bile duct (CBD) cannulation attempts in endoscopic retrograde cholangiopancreatography (ERCP). After GW passage into the pancreas, the ...most effective maneuver for CBD cannulation and pancreatitis prevention has not been determined.
to study CBD cannulation and post-ERCP pancreatitis rates when a pancreatic stent is inserted after an unintentional GW cannulation of the pancreatic duct.
a retrospective analysis of patients undergoing ERCP for biliary drainage that were included prospectively into a database. After unintentional GW cannulation of the pancreatic duct, a straight 5-Fr and 4-cm long plastic stent was inserted. The stents had no internal flaps to facilitate expulsion. CBD cannulation attempts were made above the stent. A pancreatic sphincterotomy was performed in patients older than 60 years before stent insertion.
a total of 46 pancreatic stents were inserted during 154 ERCP (29.8%) procedures. In the stent group, CBD cannulation was accomplished in 44/46 (95.6%) subjects. A total of 21/46 (45.6%) pancreatic sphincterotomies were performed. Only 1/46 (2.17%) mild pancreatitis cases were observed and most stents were spontaneously expelled.
in this study, the CBD was eventually reached with the insertion of a plastic pancreatic stent after an unintentional GW passage into the pancreatic duct while attempting a CBD cannulation. No adverse events were observed following pancreatic stent insertion.
Pancreatic cancer is one of the deadliest cancers worldwide, mainly due to late diagnosis. Therefore, there is an urgent need for novel diagnostic approaches to identify the disease as early as ...possible. We have developed a diagnostic assay for pancreatic cancer based on the detection of naturally occurring tumor associated autoantibodies against Mucin‐1 (MUC1) using engineered glycopeptides on nanoparticle probes. We used a structure‐guided approach to develop unnatural glycopeptides as model antigens for tumor‐associated MUC1. We designed a collection of 13 glycopeptides to bind either SM3 or 5E5, two monoclonal antibodies with distinct epitopes known to recognize tumor associated MUC1. Glycopeptide binding to SM3 or 5E5 was confirmed by surface plasmon resonance and rationalized by molecular dynamics simulations. These model antigens were conjugated to gold nanoparticles and used in a dot‐blot assay to detect autoantibodies in serum samples from pancreatic cancer patients and healthy volunteers. Nanoparticle probes with glycopeptides displaying the SM3 epitope did not have diagnostic potential. Instead, nanoparticle probes displaying glycopeptides with high affinity for 5E5 could discriminate between cancer patients and healthy controls. Remarkably, the best‐discriminating probes show significantly better true and false positive rates than the current clinical biomarkers CA19‐9 and carcinoembryonic antigen (CEA).
Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in consumer products, which contributes to widespread exposure of humans. OPE diester metabolites in urine have been ...used as biomarkers of human exposure to these chemicals. Little is known, however, about occurrence and temporal variability in urinary concentrations of OPE metabolites in humans. In this study, 11 OPE metabolites were measured in 213 urine samples collected from 19 volunteers from Albany, New York, United States, at 3-day intervals for five weeks to investigate temporal variability in urinary concentrations. Diphenyl phosphate (DPHP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the major OPE metabolites, detected in all urine samples at specific gravity (SG)-adjusted concentrations (geometric mean, GM) of 1060 and 414 pg/mL and creatinine (Cr)-adjusted concentration (GM) of 404 and 156 ng/g, respectively. Inter-day variability in urinary OPE metabolite concentrations in 19 individuals was evaluated by intraclass correlation coefficients (ICCs). The inter-day variability in Cr-adjusted OPE metabolite concentrations (ICC: 0.31–0.67) was lower than those of SG-adjusted (ICC: 0.19–0.71) and unadjusted urinary concentrations (ICC: 0.24–0.74). BDCIPP (ICC: 0.68) and bis(2-chloroethyl) phosphate (BCEP) (ICC: 0.67) concentrations showed a moderate-to-high reliability over the sampling period, whereas the other nine OPE metabolites exhibited a moderate reliability (ICC: 0.31–0.55). Urine samples were further stratified by gender, age, ethnicity, and body mass index (BMI). The concentrations of BDCIPP and DPHP were significantly lower in males with normal BMI (BMI: 18.5–25 kg/m2) than in females and other BMI categories (p < 0.01). Relatively high ICCs, indicating low inter-day variability, were observed for males (ICC: 0.35–0.71) of 30–40 years of age (ICC: 0.34–0.87) with normal BMI (ICC: 0.28–0.64). The daily exposure doses to OPEs were estimated from urinary concentrations of corresponding OPE metabolites. The estimated doses of triphenyl phosphate (TPHP) and triethyl phosphate (TEP), based on median urinary concentrations of their metabolites, were 19.4 and 24.0 ng/kg bw/day, and the exposure dose to ∑OPEs was estimated at 65.3 ng/kg bw/day. Overall, our results indicate a high ICC for Cr-adjusted urinary concentrations of 11 OPE metabolites in urine.
•Interday variability in urinary concentrations of OPE metabolites was studied.•Diphenyl phosphate and bis(1,3-dichloro-2-propyl) phosphate were the major OPE metabolites in urine.•Urine collected longitudinally for five weeks from volunteers showed moderate variability.•Creatinine adjustment of urinary OPE metabolite levels improved ICC and increased reproducibility.•Age, gender, race and BMI had some effects on ICC.
Oxidative stress in humans is affected by the health and nutritional status as well as exposure to external environmental factors. To evaluate the effects of external factors, an assessment of ...baseline levels as well as diurnal variations in oxidative stress status of healthy individuals is needed. In this study, we examined intra- and inter-individual variability of oxidative stress biomarkers (OSBs) of lipids (malondialdehyde MDA and four F2-isoprostane isomers, namely, 8-isoprostaglandinF2α 8-PGF2α, 11β-prostaglandinF2α 11-PGF2α, 15(R)-prostaglandinF2α 15-PGF2α, and 8-iso,15(R)-prostaglandinF2α 8,15-PGF2α); proteins (o,o′-dityrosine diY); and DNA (8-hydroxy-2′-deoxyguanosine 8-OHdG) in urine from healthy individuals. The significance of creatinine correction, which is typically used to account for urinary dilution, on OSB concentrations was evaluated. Analysis of 515 urine samples, collected longitudinally from 19 healthy individuals daily for over a month, showed inter-individual coefficient of variation (CV) in concentrations from 112% for MDA to 272% for 15-PGF2α. Intra-individual CV in concentrations ranged from 29% for 8-OHdG to 149% for 15-PGF2α. MDA was the most abundant OSB found in urine. The intra- and inter-individual variability in F2-isoprostane concentrations were higher than the values calculated for diY, 8-OHdG, and MDA. All seven OSB concentrations were significantly correlated with each other and with creatinine. Creatinine normalization of OSB concentrations improved predictability in OSB concentrations over time. Our results suggest that 8-OHdG, showing the highest ICC (0.96), yielded more reproducible measurements with a low CV, and is the most suitable biomarker of OSB in spot urine samples. The measured concentrations and diurnal variability in urinary OSB levels in healthy individuals reported in this study are useful as a benchmark for future toxicological and epidemiological studies.
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•Variability in oxidative stress biomarkers was measured for over a month in urine of healthy individuals.•Urinary oxidative stress markers of DNA, lipids and protein are correlated with creatinine.•MDA, 8-OHdG, diY and PGF2α showed considerable inter-person variability.•8-OHdG levels showed the lowest intra- and inter-individual variability.
•Non-targeted SPME-GC/MS volatolomics applied to the discovery of new biomarkers.•Control-case study for the detection of pancreatic cancer (PAC) biomarkers.•Highly sensitive biomarkers, with AUC ...above 0.9, were found in serum.•Eleven PAC biomarkers were validated with an independent set of samples.•Butoxymethylbenzene, toluene, 2ethyl-1hexanol and pentylbenzene are PAC indicators.
The discovery of new diagnostic tools for the early detection of diseases with poor prognosis such as pancreatic adenocarcinoma (PAC) is of high importance. The results from a control-case study (20 PAC patients, 19 healthy controls) for the search of new biomarkers of pancreatic cancer based in differences in the serum volatolome are presented in this work. Volatolomics were performed following a non-targeted HS-SPME-GC/MS approach, and a total of 433 volatile organic compounds (VOCs) was detected in the human serum samples. Of these, 125 VOC indexes showed a significant variation when controls and patients were compared (p-value < 0.05). Bonferroni corrected p-values < 0.05 were found for 40 features. PCA analysis showed the control-PAC discrimination capability of VOCs in serum, and PLS-DA was performed to select the best candidate biomarkers for the diagnosis of PAC. For the 40 selected VOCs, calculated areas under the curve (AUC) ranged from 0.98 to 0.85, and 11 of them were successfully validated using an independent set of samples (5 PAC patients, 5 healthy controls). Four of the proposed PAC biomarkers were identified as toluene, 2-ethyl-1-hexanol, pentylbenzene, and butoxymethylbenzene. Combinations of the identified PAC biomarkers were tested and showed AUC > 0.90, with the more promising candidate being butoxymethylbenzene (AUC = 0.98).
Environmental chemical exposures have been associated with cancer, diabetes, hormonal and immunological disorders, and cardiovascular diseases. Some direct effects of chemical exposure that are ...precursors to adverse health outcomes, including oxidative stress, nitrative stress, hormonal imbalance, neutrophilia, and eosinophilia, can be assessed through the analysis of biomarkers in urine. In this study, we describe a novel methodology for the determination of 19 biomarkers of health effects: malondialdehyde (MDA), 8-isoprostaglandin-F
2α
(8-PGF
2α
), 11-β-prostaglandin-F
2α
(11-PGF
2α
), 15-prostaglandin-F
2α
(15-PGF
2α
), 8-iso-15-prostaglandin-F
2α
(8,15-PGF
2α
), 8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-HdG), 8-hydroxyguanine (8-HG), dityrosine (diY), allantoin (Alla), and two metabolic products of 4-hydroxynonenal (HNE), namely 4-hydroxy-2-nonenal glutathione (HNE-GSH) and 4-hydroxy-2-nonenal mercapturic acid (HNE-MA) (in total, 12 oxidative stress biomarkers, OSBs); 8-nitroguanosine (8-NdG), 8-nitroguanine (8-NG), and 3-nitrotyrosine (NY) (3 nitrative stress biomarkers, NSBs); chlorotyrosine (CY) and bromotyrosine (BY) (2 inflammatory biomarkers); and the advanced glycation end-products (AGEs)
N
ε
-carboxymethyllysine (CML) and
N
ε
-carboxyethyllysine (CEL) (2 metabolic disorder biomarkers). Since these biomarkers are trigged by a variety of environmental insults and produced by different biomolecular pathways, their selective and sensitive determination in urine would help broadly elucidate the pathogenesis of diseases mediated by environmental factors.
Graphical abstract
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•Hydroxy naphthalene was the abundant PAH metabolite found in urine.•Intra-class correlation coefficients (ICCs) showed moderate predictability for OHNap.•ICC values for other OH-PAHs ...were poor, which suggested variable exposures.•Oxidative stress markers were longitudinally associated with PAH exposure.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants. Urinary concentrations of mono-hydroxylated metabolites of PAHs (OH-PAHs) have been used as biomarkers of these chemicals’ exposure in humans. Little is known, however, with regard to intra- and inter-individual variability in OH-PAH concentrations and their association with oxidative stress. We conducted a longitudinal study of measurement of urinary concentrations of 15 OH-PAHs and 7 oxidative stress biomarkers (OSBs) of DNA damage 8-hydroxy-2′-deoxyguanosine (8-OHdG), lipid malondialdehyde (MDA) and F2-isoprostanes (PGF2α) and protein o,o′-dityrosine (diY) peroxidation in 19 individuals for 44 consecutive days. Metabolites of naphthalene (OHNap), fluorene (OHFlu), phenanthrene (OHPhe), and pyrene (OHPyr) were found in >70% of 515 urine samples analyzed, at sum concentrations (∑OH-PAH) measured in the range of 0.46–60 ng/mL. After adjusting for creatinine, OHNap and ∑OH-PAH concentrations exhibited moderate predictability, with intra-class correlation coefficients (ICCs) ranging from 0.359 to 0.760. However, ICC values were low (0.001–0.494) for OHFlu, OHPhe, and OHPyr, which suggested poor predictability for these PAH metabolites. Linear mixed-effects analysis revealed that an unit increase in ∑OH-PAH concentration corresponded to 4.5%, 5.3%, 20%, and 21% increase in respective urinary 8-OHdG, MDA, PGF2α, and diY concentrations, suggesting an association with oxidative damage to DNA, lipids, and proteins. The daily intakes of PAHs, calculated from urinary concentrations of OH-PAHs, were 10- to 100-fold below the current reference doses. This study provides valuable information to design sampling strategies in biomonitoring studies and in assigning exposure classifications of PAHs in epidemiologic studies.
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