In developed countries, sustainability is increasingly an active agenda topic for businesses. Yet a view on what sustainability exactly means in the minds of consumers is missing. In response to this ...research opportunity, online panel respondents from seven advanced economies (France, UK, Germany, Belgium, Sweden, Netherlands, Australia,
N
= 5620) were surveyed in two cross-sectional waves. Factor analytical results show that consumers associate sustainability with three key subdimensions: ‘social equality’ (e.g., fair wages), ‘circularity’ (e.g., recycling) and ‘naturalness’ (e.g., avoiding use of pesticides and GMOs). This observation offers inspiration to update the traditional two-dimensional (social vs. environmental) structure of sustainability advanced in previous literature. In addition, the identified ‘naturalness’ dimension may point to a new route to stimulate pro-environmental behavior as it has both a strong link with the environment and may introduce an affective undertone. We discuss theoretical and managerial implications, and report observed country, gender, and age differences.
Obeticholic acid (OCA) is an agonist of the nuclear bile acid receptor farnesoid X receptor, which regulates hepatic bile acid metabolism. We tested whether OCA treatment would influence hepatic ...transport of conjugated bile acids in patients with primary biliary cholangitis (PBC) who responded inadequately to treatment with ursodeoxycholic acid (UDCA).
Eight UDCA-treated patients with PBC with alkaline phosphatase ≥1.5 times the upper limit of normal range participated in a double-blind, placebo-controlled study. While continuing on UDCA, the patients were randomised to two 3-month crossover treatment periods with placebo and OCA, in random order, separated by a 1-month washout period without study treatment. After each of the two treatment periods, we determined rate constants for transport of conjugated bile acids between blood, hepatocytes, biliary canaliculi, and bile ducts by positron emission tomography of the liver using the conjugated bile acid tracer N-methyl-11Ccholylsarcosine (11C-CSar). The hepatic blood perfusion was measured using infusion of indocyanine green and Fick's principle.
Compared with placebo, OCA increased hepatic blood perfusion by a median of 11% (p = 0.045), the unidirectional uptake clearance of 11C-CSar from blood into hepatocytes by a median of 11% (p = 0.01), and the rate constant for secretion of 11C-CSar from hepatocytes into biliary canaliculi by a median of 73% (p = 0.03). This resulted in an OCA-induced decrease in the hepatocyte residence time of 11C-CSar by a median of 30% (p = 0.01), from group median 11 min to 8 min.
This study of UDCA-treated patients with PBC showed that, compared with placebo, OCA increased the hepatic transport of the conjugated bile acid tracer 11C-CSar, and thus endogenous conjugated bile acids, from hepatocytes into biliary canaliculi. As a result, OCA reduced the time hepatocytes are exposed to potentially cytotoxic bile acids.
Primary biliary cholangitis is a chronic liver disease in which the small bile ducts are progressively destroyed. We tested whether the treatment with obeticholic acid (OCA) would improve liver excretion of bile acids compared with placebo in 8 patients with primary biliary cholangitis. A special scanning technique (PET scan) showed that OCA increased the transport of bile acids from blood to bile. OCA thereby reduced the time that potentially toxic bile acids reside in the liver by approximately one-third.
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•A randomised, placebo-controlled, crossover PET study of 8 patients with PBC.•OCA enhances secretion of conjugated bile acids from hepatocytes into biliary canaliculi.•OCA increases hepatic blood perfusion and uptake clearance of conjugated bile acids.•OCA reduces the time hepatocytes are exposed to potentially toxic bile acids.
Introduction:
Despite the decades long use of 11Cpalmitate positron emission tomography (PET)/computed tomography in basic metabolism studies, only personal communications regarding dosimetry and ...biodistribution data have been published.
Methods:
Dosimetry and biodistribution studies were performed in 2 pigs and 2 healthy volunteers by whole-body 11Cpalmitate PET scans. Metabolite studies were performed in 40 participants (healthy and with type 2 diabetes) under basal and hyperinsulinemic conditions. Metabolites were estimated using 2 approaches and subsequently compared: Indirect 11CCO2 release and parent 11Cpalmitate measured by a solid-phase extraction (SPE) method. Finally, myocardial fatty acid uptake was calculated in a patient cohort using input functions derived from individual metabolite correction compared with population-based metabolite correction.
Results:
In humans, mean effective dose was 3.23 (0.02) µSv/MBq, with the liver and myocardium receiving the highest absorbed doses. Metabolite correction using only 11CCO2 estimates underestimated the fraction of metabolites in studies lasting more than 20 minutes. Population-based metabolite correction showed excellent correlation with individual metabolite correction in the cardiac PET validation cohort.
Conclusion:
First, mean effective dose of 11Cpalmitate is 3.23 (0.02) µSv/MBq in humans allowing multiple scans using ∼300 MBq 11Cpalmitate, and secondly, population-based metabolite correction compares well with individual correction.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
N-methyl-11Ccholylsarcosine (11CCSar) is a tracer for imaging and quantitative assessment of intrahepatic cholestatic liver diseases and drug-induced cholestasis by positron emission tomography ...(PET). The purpose of this study is to determine whole-body biodistribution and dosimetry of 11CCSar in healthy humans. The results are compared with findings in a patient with primary sclerosing cholangitis (PSC) and a patient with primary biliary cholangitis (PBC) as well as with preclinical findings in pigs. Radiosynthesis and quality control for preparation of 11CCSar for clinical use are also presented.
Radiosynthesis and quality control of 11CCSar were set up in compliance with Danish/European regulations. Both healthy participants (3 females, 3 males) and patients underwent whole-body PET/CT to determine the biodistribution of 11CCSar. The two patients were under treatment with ursodeoxycholic acid at the time of the study. Dosimetry was estimated from the PET data using the Olinda 2.0 software.
The radiosynthesis provided 11CCSar in a solution ready for injection. The biodistribution studies revealed that gallbladder wall, small intestine, and liver were critical organs in both healthy participants and patients with the gallbladder wall receiving the highest dose (up to 0.5 mGy/MBq). The gender-averaged (±SD) effective dose for the healthy participants was 6.2 ± 1.4 μSv/MBq. The effective dose for the PSC and the PBC patient was 5.2 and 7.0 μSv/MBq, respectively.
A radiosynthesis for preparation of 11CCSar for clinical use was developed and approved by the Danish Medicines Agency. The most critical organ was the gallbladder wall although the amount of 11CCSar in the gallbladder was found to vary significantly between individuals. The estimated effective dose for humans was comparable to that estimated in anesthetized pigs although the absorbed dose estimates to some organs, such as the stomach, was different.
11CCSar PET/CT enables detailed quantitative assessment of patients with cholestatic liver disease by tracing the separate hepatobiliary transport steps of endogenous bile acids. The present work offers a radiosynthetic method and dosimetry data suitable for clinical implementation of 11CCSar.
During cholestasis, accumulation of conjugated bile acids may occur in the liver and lead to hepatocellular damage. Inspired by our recent development of N-11C-methyl-glycocholic acid -- that is, ...11C-cholylsarcosine -- a tracer for PET of the endogenous glycine conjugate of cholic acid, we report here a radiosynthesis of N-11C-methyl-taurine-conjugated bile acids and biodistribution studies in pigs by PET/CT. A radiosynthesis of N-11C-methyl-taurine-conjugated bile acids was developed and used to prepare N-11C-methyl-taurine conjugates derived from cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic acid. The lipophilicity of these new tracers was determined by reversed-phase thin-layer chromatography. The effect of lipophilicity and structure on the biodistribution was investigated in pigs by PET/CT using the tracers derived from cholic acid (3 alpha -OH, 7 alpha -OH, 12 alpha -OH), ursodeoxycholic acid (3 alpha -OH, 7 beta -OH), and lithocholic acid (3 alpha -OH). The radiosyntheses of the N-11C-methyl-taurine-conjugated bile acids proceeded with radiochemical yields of 61% (decay-corrected) or greater and radiochemical purities greater than 99%. PET/CT in pigs revealed that the tracers were rapidly taken up by the liver and secreted into bile. There was no detectable radioactivity in urine. Significant reflux of N-11C-methyl-taurolithocholic acid into the stomach was observed. We have successfully developed a radiosynthesis of N-11C-methyl-taurine-conjugated bile acids. These tracers behave in a manner similar to endogenous taurine-conjugated bile acids in vivo and are thus promising for functional PET of patients with cholestatic diseases.
During cholestasis, accumulation of conjugated bile acids may occur in the liver and lead to hepatocellular damage. Inspired by our recent development of N-...C-methyl-glycocholic acid -- that is, ......C-cholylsarcosine -- a tracer for PET of the endogenous glycine conjugate of cholic acid, we report here a radiosynthesis of N-...C-methyl-taurine-conjugated bile acids and biodistribution studies in pigs by PET/CT. A radiosynthesis of N-...C-methyl-taurine-conjugated bile acids was developed and used to prepare N-...C-methyl-taurine conjugates derived from cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic acid. The lipophilicity of these new tracers was determined by reversed-phase thin-layer chromatography. The effect of lipophilicity and structure on the biodistribution was investigated in pigs by PET/CT using the tracers derived from cholic acid (3α-OH, 7α-OH, 12α-OH), ursodeoxycholic acid (3α-OH, 7...-OH), and lithocholic acid (3α-OH). The radiosyntheses of the N-...C-methyl-taurine-conjugated bile acids proceeded with radiochemical yields of 61% (decay-corrected) or greater and radiochemical purities greater than 99%. PET/CT in pigs revealed that the tracers were rapidly taken up by the liver and secreted into bile. There was no detectable radioactivity in urine. Significant reflux of N-...C-methyl-taurolithocholic acid into the stomach was observed. We have successfully developed a radiosynthesis of N-...C-methyl-taurine-conjugated bile acids. These tracers behave in a manner similar to endogenous taurine-conjugated bile acids in vivo and are thus promising for functional PET of patients with cholestatic diseases. (ProQuest: ... denotes formulae/symbols omitted.)
During cholestasis, accumulation of conjugated bile acids may occur in the liver and lead to hepatocellular damage. Inspired by our recent development of N-(11)C-methyl-glycocholic acid-that is, ...(11)C-cholylsarcosine-a tracer for PET of the endogenous glycine conjugate of cholic acid, we report here a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids and biodistribution studies in pigs by PET/CT.
A radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids was developed and used to prepare N-(11)C-methyl-taurine conjugates derived from cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic acid. The lipophilicity of these new tracers was determined by reversed-phase thin-layer chromatography. The effect of lipophilicity and structure on the biodistribution was investigated in pigs by PET/CT using the tracers derived from cholic acid (3α-OH, 7α-OH, 12α-OH), ursodeoxycholic acid (3α-OH, 7β-OH), and lithocholic acid (3α-OH).
The radiosyntheses of the N-(11)C-methyl-taurine-conjugated bile acids proceeded with radiochemical yields of 61% (decay-corrected) or greater and radiochemical purities greater than 99%. PET/CT in pigs revealed that the tracers were rapidly taken up by the liver and secreted into bile. There was no detectable radioactivity in urine. Significant reflux of N-(11)C-methyl-taurolithocholic acid into the stomach was observed.
We have successfully developed a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids. These tracers behave in a manner similar to endogenous taurine-conjugated bile acids in vivo and are thus promising for functional PET of patients with cholestatic diseases.
The increasing effects of climate change and the resulting trends, such as the rise of green energy and e-mobility, are driving the demand for metals and rare earths. To meet this demand, deep-sea ...mining is likely to become necessary in the future. However, it is important to recognize that the extraction of these resources may have a significant impact on the environment. One critical issue is the generation of sediment plumes resulting from mining equipment. In this paper, the development and evaluation of a customized open-source based turbidity monitoring system designed to detect sediment plumes during a pilot test of seafloor massive sulphide mining is presented. The development process utilizes the open-source sensor prototyping platform OpenAquaSense to create a cost-efficient turbidity monitoring system with a broad adaptive measuring range. The sensors are calibrated and evaluated through pressure tank tests and sedimentation experiments. Ultimately, the developed system proves to be suitable for the intended application and serves as a basis for the development of a system for use in field experiments.
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