| 1. |
- Nijsingh, Niels, 1977, et al.
(författare)
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Managing pollution from antibiotics manufacturing: charting actors, incentives and disincentives
- 2019
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Ingår i: Environmental health. - : Springer Science and Business Media LLC. - 1476-069X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background Emissions of high concentrations of antibiotics from manufacturing sites select for resistant bacteria and may contribute to the emergence of new forms of resistance in pathogens. Many scientists, industry, policy makers and other stakeholders recognize such pollution as an unnecessary and unacceptable risk to global public health. An attempt to assess and reduce such discharges, however, quickly meets with complex realities that need to be understood to identify effective ways to move forward. This paper charts relevant key actor-types, their main stakes and interests, incentives that can motivate them to act to improve the situation, as well as disincentives that may undermine such motivation. Methods The actor types and their respective interests have been identified using research literature, publicly available documents, websites, and the knowledge of the authors. Results Thirty-three different actor-types were identified, representing e.g. commercial actors, public agencies, states and international institutions. These are in complex ways connected by interests that sometimes may conflict and sometimes pull in the same direction. Some actor types can act to create incentives and disincentives for others in this area. Conclusions The analysis demonstrates and clarifies the challenges in addressing industrial emissions of antibiotics, notably the complexity of the relations between different types of actors, their international dependency and the need for transparency. The analysis however also suggests possible ways of initiating incentive-chains to eventually improve the prospects of motivating industry to reduce emissions. High-resource consumer states, especially in multinational cooperation, hold a key position to initiate such chains.
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| 2. |
- Solinas, Giovanni, et al.
(författare)
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An adipoincretin effect links adipostasis with insulin secretion.
- 2024
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Ingår i: Trends in endocrinology and metabolism: TEM. - 1879-3061. ; 35:6, s. 466-477
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Forskningsöversikt (refereegranskat)abstract
- The current paradigm for the insulin system focuses on the phenomenon of glucose-stimulated insulin secretion and insulin action on blood glucose control. This historical glucose-centric perspective may have introduced a conceptual bias in our understanding of insulin regulation. A body of evidence demonstrating that in vivo variations in blood glucose and insulin secretion can be largely dissociated motivated us to reconsider the fundamental design of the insulin system as a control system for metabolic homeostasis. Here, we propose that a minimal glucose-centric model does not accurately describe the physiological behavior of the insulin system and propose a new paradigm focusing on the effects of incretins, arguing that under fasting conditions, insulin is regulated by an adipoincretin effect.
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| 3. |
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| 4. |
- Andersson, Sören, 1957-, et al.
(författare)
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CHIMERIC MOMP ANTIGEN
- 2015
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Patent (populärvet., debatt m.m.)
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| 5. |
- Eriksson, Leif A., 1964-, et al.
(författare)
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Tetrazole derivatives as cytochrome p450 inhibitors
- 2019
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Patent (populärvet., debatt m.m.)abstract
- According to the invention there is provided a compound of formula I, wherein R1 and R2 have meanings given in the description, which compounds are useful in the treatment of skin disorders and other diseases.
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| 6. |
- Rube, Tanja, et al.
(författare)
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Development of the Swedish anticholinergic burden scale (Swe-ABS).
- 2023
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Ingår i: BMC geriatrics. - 1471-2318. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Drugs with anticholinergic properties are associated with cognitive adverse effects, especially in patients vulnerable to central muscarinic antagonism. A variety of drugs show weak, moderate or strong anticholinergic effects. Therefore, the cumulative anticholinergic burden should be considered in patients with cognitive impairment. This study aimed to develop a Swedish Anticholinergic Burden Scale (Swe-ABS) to be used in health care and research.A systematic literature review was conducted in PubMed and Ovid Embase to identify previously published tools quantifying anticholinergic drug burden (i.e., exposure). Drugs and grading scores (0-3, no to high anticholinergic activity) were extracted from identified lists. Enteral and parenteral drugs authorized in Sweden were included. Drugs with conflicting scores in the existing lists were assessed by an expert group. Two drugs that were not previously assessed were also added to the evaluation process.The systematic literature search identified the following nine anticholinergic burden scales: Anticholinergic Activity Scale, Anticholinergic Burden Classification, updated Anticholinergic Cognitive Burden scale, Anticholinergic Drug Scale, Anticholinergic Load Scale, Anticholinergic Risk Scale, updated Clinician-rated Anticholinergic Scale, German Anticholinergic Burden Scale and Korean Anticholinergic Burden Scale. A list of drugs with significant anticholinergic effects provided by The Swedish National Board of Health and Welfare was included in the process. The suggested Swe-ABS consists of 104 drugs scored as having weak, moderate or strong anticholinergic effects. Two hundred and fifty-six drugs were listed as having no anticholinergic effects based on evaluation in previous scales. In total, 62 drugs were assessed by the expert group.Swe-ABS is a simplified method to quantify the anticholinergic burden and is easy to use in clinical practice. Publication of this scale might make clinicians more aware of drugs with anticholinergic properties and patients' total anticholinergic burden. Further research is needed to validate the Swe-ABS and evaluate anticholinergic exposure versus clinically significant outcomes.
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| 7. |
- Zhang, C., et al.
(författare)
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The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease
- 2020
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.
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| 8. |
- Rolfö, Linda, et al.
(författare)
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Predictors of Preference for the Activity-based Flexible Office
- 2019
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Ingår i: Human Systems Engineering and Design. - Cham : Springer. - 9783030020521 - 9783030020538 ; 876, s. 547-553
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Konferensbidrag (refereegranskat)abstract
- Activity-based Flexible Offices (A-FOs) are implemented with varying degree of success. Employees relocate from cell or open-plan offices, from different organizational backgrounds, varying design and implementation processes, and have different types of work tasks. This study aims at investigating whether preference for the A-FO correlate with these preconditions. The results from Chi-square tests and Spearman’s non-parametric correlation of post-relocation questionnaires distributed to 11 A-FO sites, showed that a high preference for the A-FO correlated strongest with an A-FO preference prior to relocation, being a former open-plan office occupier and with frequent performance of innovation. Low preference for the A-FO correlated with frequent performance of concentration demanding tasks. Working with tasks with high confidentiality did not predict the preference ratings.
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| 9. |
- Senkowski, Wojciech
(författare)
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High-throughput screening using multicellular tumor spheroids to reveal and exploit tumor-specific vulnerabilities
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- High-throughput drug screening (HTS) in live cells is often a vital part of the preclinical anticancer drug discovery process. So far, two-dimensional (2D) monolayer cell cultures have been the most prevalent model in HTS endeavors. However, 2D cell cultures often fail to recapitulate the complex microenvironments of in vivo tumors. Monolayer cultures are highly proliferative and generally do not contain quiescent cells, thought to be one of the main reasons for the anticancer therapy failure in clinic. Thus, there is a need for in vitro cellular models that would increase predictive value of preclinical research results. The utilization of more complex three-dimensional (3D) cell cultures, such as multicellular tumor spheroids (MCTS), which contain both proliferating and quiescent cells, has therefore been proposed. However, difficult handling and high costs still pose significant hurdles for application of MCTS for HTS.In this work, we aimed to develop novel assays to apply MCTS for HTS and drug evaluation. We also set out to identify cellular processes that could be targeted to selectively eradicate quiescent cancer cells. In Paper I, we developed a novel MCTS-based HTS assay and found that nutrient-deprived and hypoxic cancer cells are selectively vulnerable to treatment with inhibitors of mitochondrial oxidative phosphorylation (OXPHOS). We also identified nitazoxanide, an FDA-approved anthelmintic agent, to act as an OXPHOS inhibitor and to potentiate the effects of standard chemotherapy in vivo. Subsequently, in Paper II we applied the high-throughput gene-expression profiling method for MCTS-based drug screening. This led to discovery that quiescent cells up-regulate the mevalonate pathway upon OXPHOS inhibition and that the combination of OXPHOS inhibitors and mevalonate pathway inhibitors (statins) results in synergistic toxicity in this cell population. In Paper III, we developed a novel spheroid-based drug combination-screening platform and identified a set of molecules that synergize with nitazoxanide to eradicate quiescent cancer cells. Finally, in Paper IV, we applied our MCTS-based methods to evaluate the effects of phosphodiesterase (PDE) inhibitors in PDE3A-expressing cell lines.In summary, this work illustrates how MCTS-based HTS yields potential to reveal and exploit previously unrecognized tumor-specific vulnerabilities. It also underscores the importance of cell culture conditions in preclinical drug discovery endeavors.
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| 10. |
- Nyandoro, Stephen S., 1975, et al.
(författare)
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N-Cinnamoyltetraketide Derivatives from the Leaves of Toussaintia orientalis
- 2015
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Ingår i: Journal of natural products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 78:8, s. 2045-2050
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Tidskriftsartikel (refereegranskat)abstract
- Seven N-cinnamoyltetraketides (1–7), including the new Z-toussaintine E (2), toussaintine F (6), and toussaintine G (7), were isolated from the methanol extract of the leaves of Toussaintia orientalis using column chromatography and HPLC. The configurations of E-toussaintine E (1) and toussaintines A (3) and D (5) are revised based on single-crystal X-ray diffraction data from racemic crystals. Both the crude methanol extract and the isolated constituents exhibit antimycobacterial activities (MIC 83.3–107.7 μM) against the H37Rv strain of Mycobacterium tuberculosis. Compounds 1, 3, 4, and 5 are cytotoxic (ED50 15.3–105.7 μM) against the MDA-MB-231 triple negative aggressive breast cancer cell line.
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| 11. |
- Mohammadi, Elyas, et al.
(författare)
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Applications of Genome-Wide Screening and Systems Biology Approaches in Drug Repositioning
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:9, s. 1-24
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Forskningsöversikt (refereegranskat)abstract
- Simple Summary Drug repurposing is an accelerated route for drug development and a promising approach for finding medications for orphan and common diseases. Here, we compiled databases that comprise both computationally- or experimentally-derived data, and categorized them based on quiddity and origin of data, further focusing on those that present high throughput omic data or drug screens. These databases were then contextualized with genome-wide screening methods such as CRISPR/Cas9 and RNA interference, as well as state of art systems biology approaches that enable systematic characterizations of multi-omic data to find new indications for approved drugs or those that reached the latest phases of clinical trials. Modern drug discovery through de novo drug discovery entails high financial costs, low success rates, and lengthy trial periods. Drug repositioning presents a suitable approach for overcoming these issues by re-evaluating biological targets and modes of action of approved drugs. Coupling high-throughput technologies with genome-wide essentiality screens, network analysis, genome-scale metabolic modeling, and machine learning techniques enables the proposal of new drug-target signatures and uncovers unanticipated modes of action for available drugs. Here, we discuss the current issues associated with drug repositioning in light of curated high-throughput multi-omic databases, genome-wide screening technologies, and their application in systems biology/medicine approaches.
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| 12. |
- Molinaro, Angela, et al.
(författare)
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Insulin-Driven PI3K-AKT Signaling in the Hepatocyte Is Mediated by Redundant PI3Kα and PI3Kβ Activities and Is Promoted by RAS.
- 2019
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 29:6
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Tidskriftsartikel (refereegranskat)abstract
- Phosphatidylinositol-3-kinase (PI3K) activity is aberrant in tumors, and PI3K inhibitors are investigated as cancer therapeutics. PI3K signaling mediates insulin action in metabolism, but the role of PI3K isoforms in insulin signaling remains unresolved. Defining the role of PI3K isoforms in insulin signaling is necessary for a mechanistic understanding of insulin action and to develop PI3K inhibitors with optimal therapeutic index. We show that insulin-driven PI3K-AKT signaling depends on redundant PI3Kα and PI3Kβ activities, whereas PI3Kδ and PI3Kγ are largely dispensable. We have also found that RAS activity promotes AKT phosphorylation in insulin-stimulated hepatocytes and that promotion of insulin-driven AKT phosphorylation by RAS depends on PI3Kα. These findings reveal the detailed mechanism by which insulin activates AKT, providing an improved mechanistic understanding of insulin signaling. This improved model for insulin signaling predicts that isoform-selective PI3K inhibitors discriminating between PI3Kα and PI3Kβ should bedosed below their hyperglycemic threshold to achieve isoform selectivity.
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| 13. |
- Lesén, Eva, 1982, et al.
(författare)
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Is the level of patient co-payment for medicines associated with refill adherence in Sweden?
- 2014
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 24:1, s. 85-90
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Tidskriftsartikel (refereegranskat)abstract
- In the Swedish reimbursement scheme, the co-payment is based on the price of the product and decreases in a stepwise manner as the total accumulated co-payment increases. The aim of this study was to analyse how refill adherence in Sweden varies according to patient's co-payment level for medicines, with antiepileptic drug (AED) use as an example.
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| 14. |
- Insulander Björk, Klara, 1982, et al.
(författare)
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Experimental determination of concentration factors of Mn, Zn and I in the phytoplankton species Phaeodactylum Tricornutum
- 2023
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Ingår i: Journal of Environmental Radioactivity. - : Elsevier BV. - 0265-931X .- 1879-1700. ; 261
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Tidskriftsartikel (refereegranskat)abstract
- Anthropogenic radionuclides released into the environment cause a radiation dose to wildlife and humans which must be quantified, both to assess the effect of normal releases, and to predict the consequences of a larger, unplanned release. To estimate the spread of the radioactive elements, the ecosystem around release points is modelled, and element uptake is usually quantified by concentration factors (CF), which relates the concentration of an element in an organism to the concentration of the same element in a medium under equilibrium conditions. In this work, we experimentally determine some phytoplankton CF that are needed for improved modelling of the marine ecosystems around nuclear facilities and release points. CFs that require better determination have been identified through literature search. Sensitivity studies, using the currently used ecosystem modelling software PREDO, show that for most studied groups, the dose committed by the respective radionuclides is almost proportional to the corresponding phytoplankton CFs. In the present work, CFs are determined through laboratory experiments with cultured phytoplankton and radionuclides of the concerned elements, assessing the element uptake by the phytoplankton through detection of the emitted radiation. The three CF assessed in this work were those for manganese, zinc and iodine in phytoplankton. Conservative estimates of these CF based on the present data are 40 000 L/kg for manganese, 50 000 L/kg for zinc and 180 L/kg for iodine with the phytoplankton masses referring to their dry weight.
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| 15. |
- Zeybel, M., et al.
(författare)
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Multiomics Analysis Reveals the Impact of Microbiota on Host Metabolism in Hepatic Steatosis
- 2022
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Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; 9:11, s. 2104373-
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disease involving alterations in multiple biological processes regulated by the interactions between obesity, genetic background, and environmental factors including the microbiome. To decipher hepatic steatosis (HS) pathogenesis by excluding critical confounding factors including genetic variants and diabetes, 56 heterogenous MAFLD patients are characterized by generating multiomics data including oral and gut metagenomics as well as plasma metabolomics and inflammatory proteomics data. The dysbiosis in the oral and gut microbiome is explored and the host–microbiome interactions based on global metabolic and inflammatory processes are revealed. These multiomics data are integrated using the biological network and HS's key features are identified using multiomics data. HS is finally predicted using these key features and findings are validated in a follow-up cohort, where 22 subjects with varying degree of HS are characterized.
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| 16. |
- Altay, Özlem, et al.
(författare)
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Current Status of COVID-19 Therapies and Drug Repositioning Applications
- 2020
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Ingår i: Iscience. - : Elsevier BV. - 2589-0042. ; 23:7
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Tidskriftsartikel (refereegranskat)abstract
- The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2.
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| 17. |
- Ludvigsson, Jonas F., et al.
(författare)
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A population-based study of coeliac disease, neurodegenerative and neuroinflammatory diseases
- 2007
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 25:11, s. 1317-1327
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIt has been suggested that coeliac disease (CD) is associated with several neurological diseases. However, the evidence of such an association is inconclusive as earlier research has often been based on small numbers with retrospective data collection.AimTo use Cox regression to examine the risk of neurological disease in individuals with CD.MethodsThrough Swedish national registers we identified some 14 000 individuals with a diagnosis of CD (1964–2003) and 70 000 reference individuals matched for age, sex, calendar year and county.ResultsCoeliac disease was associated with later polyneuropathy [hazard ratio (HR) = 3.4; 95% CI = 2.3–5.1]. We found no statistically significant association between CD and subsequent multiple sclerosis (HR = 0.9; 95% CI = 0.3–2.3), Parkinson’s disease (HR = 1.2; 95% CI = 0.8–1.9), Alzheimer’s disease (HR = 1.5; 95% CI = 0.9–2.6), hereditary ataxia (HR = 1.3; 95% CI = 0.5–3.6), the symptom ataxia (HR = 1.9; 95% CI = 0.6–6.2), Huntington’s disease (HR = 1.7; 95% CI = 0.3–8.6), myasthenia gravis (HR = 0.8; 95% CI = 0.2–3.8) or spinal muscular atrophy (HR = 0.5; 95% CI = 0.1–3.8). Prior polyneuropathy was associated with subsequent CD (odds ratio = 5.4; 95% CI = 3.6–8.2).ConclusionsThe association between CD and polyneuropathy indicates shared risks. We suggest that individuals with polyneuropathy routinely undergo screening for CD. There is no notable association between CD and other neurological outcomes investigated in this study.
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| 18. |
- Saulo, Eleonor C., et al.
(författare)
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Willingness and ability to pay for artemisinin-based combination therapy in rural Tanzania
- 2008
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Ingår i: Malaria Journal. - London : BioMed Central. - 1475-2875. ; 7, s. 227-
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to analyse willingness to pay (WTP) and ability to pay (ATP) for ACT for children below five years of age in a rural setting in Tanzania before the introduction of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria. Socio-economic factors associated with WTP and expectations on anti-malaria drugs, including ACT, were also explored.MethodsStructured interviews and focus group discussions were held with mothers, household heads, health-care workers and village leaders in Ishozi, Gera and Ishunju wards in north-west Tanzania in 2004. Contingent valuation method (CVM) was used with "take-it-or-leave-it" as the eliciting method, expressed as WTP for a full course of ACT for a child and households' opportunity cost of ACT was used to assess ATP. The study included descriptive analyses with multivariate adjustment for potential confounding factors.ResultsAmong 265 mothers and household heads, 244 (92%, CI = 88%–95%) were willing to pay Tanzanian Shillings (TSh) 500 (US$ 0.46) for a child's dose of ACT, but only 55% (49%–61%) were willing to pay more than TSh 500. Mothers were more often willing to pay than male household heads (adjusted odds ratio = 2.1, CI = 1.2–3.6). Socio-economic status had no significant effect on WTP. The median annual non-subsidized ACT cost for clinical malaria episodes in an average household was calculated as US$ 6.0, which would represent 0.9% of the average total consumption expenditures as estimated from official data in 2001. The cost of non-subsidized ACT represented 7.0% of reported total annual expenditure on food and 33.0% of total annual expenditure on health care."Rapid effect," "no adverse effect" and "inexpensive" were the most desired features of an anti-malarial drug.ConclusionWTP for ACT in this study was less than its real cost and a subsidy is, therefore, needed to enable its equitable affordability. The decision taken in Tanzania to subsidize Coartem® fully at governmental health care facilities and at a consumer price of TSh 300–500 (US$ 0.28–0.46) at special designated shops through the programme of Accredited Drug Dispensing Outlets (ADDOs) appears to be well founded.
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| 19. |
- Hedna, Khedidja, 1978, et al.
(författare)
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Clinical relevance of alerts from a decision support system, PHARAO, for drug safety assessment in the older adults
- 2019
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Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 19:1, s. 164-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPHARAO is a decision support system developed to evaluate the risk for a set of either common or serious side-effects resulting from a combination of pharmacodynamic effects from a patient's medications. The objective of this study was to investigate the validity of the risk scores for the common side-effects generated by PHARAO in older patients.MethodsSide-effects included were sedation, constipation, orthostatic symptoms, anticholinergic and serotonergic effects. The alerts generated by PHARAO were tested in 745 persons 65years old. Dispensed prescriptions retrieved from the Swedish prescribed drug register were used to generate the pharmacological risk scores of patients' medications. Symptoms possibly related to side-effects were extracted from medical records data.ResultsThe PHARAO system generated 776 alerts, most often for the risk of anticholinergic symptoms. The total specificity estimates of the PHARAO system were 0.95, 0.89 and 0.78 for high, intermediate and low risk alerts, respectively. The corresponding sensitivity estimates were between 0.12 and 0.37. The negative predictive value was 0.90 and the positive predictive value ranged between 0.20-0.25.ConclusionsThe PHARAO system had a high specificity and negative predictive value to detect symptoms possibly associated with the of patients' medications, while the sensitivity and positive predictive value were low. The PHARAO system has the potential to minimise the risk of over-alerts in combination with a drug-drug interaction alert system, but should be used in connection with a medical evaluation of the patient.
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| 20. |
- Villén, Johanna, et al.
(författare)
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Estimating environmental exposure to analgesic drugs : A cross-sectional study of drug utilization patterns in the area surrounding Sweden's largest drinking water source
- 2023
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Ingår i: Environmental Advances. - : Elsevier. - 2666-7657. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Use of pharmaceuticals is continuously increasing globally and their residues are recognized as a risk for theenvironment. The aim of this study was to investigate drug utilization patterns of analgesics in relation toenvironmental hazard in the region surrounding Sweden’s largest drinking water source, Lake Mälaren. This wasexamined using sales data on pharmaceuticals from the Swedish E-health Agency. The total sales of analgesics(non-steroidal anti-inflammatory drugs, paracetamol, other non-opioid analgesics, and opioids) for both humanand veterinary use in the region were analyzed for the years 2016 to 2020, in relation to the inherent environmental hazard for each active pharmaceutical ingredient (API). We found that a total of 454 tons of analgesicswere sold in the region during these 5 years. Classifications of environmental hazard were available for 16 out ofthe 45 studied APIs, accounting for 98.8% of the total mass in kilograms. Paracetamol, ibuprofen, and acetylsalicylic acid, which are all classified as low-hazard compounds, were the most commonly sold APIs. Diclofenac, the only pharmaceutical classified as high-hazard, was the fifth most commonly sold API, with a total soldmass of 2321 kg. The majority of the total sold mass of analgesics originated from dispensed prescriptions forhuman use in urban areas. Visualization of drug sales for humans and animals in different settings can be used toidentify the environmental burden of pharmaceuticals. Based on our study, we suggest that additional measuresto reduce the impacts of pharmaceuticals on the environment should primarily be directed to prescribing physicians in urban areas and campaigns targeted at the high over-the-counter sales of diclofenac. Moreover, it isimportant to address the fact that many pharmaceuticals currently have limited data on environmental hazard.
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| 21. |
- Deyou, Tsegaye, et al.
(författare)
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Isoflavones and Rotenoids from the Leaves of Millettia oblata ssp teitensis
- 2017
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Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 80:7, s. 2060-2066
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Tidskriftsartikel (refereegranskat)abstract
- A new isoflavone, 8-prenylmilldrone (1), and four new rotenoids, oblarotenoids A-D (2-5), along with nine known compounds (6-14), were isolated from the CH2Cl2/CH3OH (1:1) extract of the leaves of Millettia oblata ssp. teitensis by chromatographic separation. The purified compounds were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of the rotenoids were established on the basis of chiroptical data and in some cases by single-crystal X-ray crystallography. Maximaisoflavone J (11) and oblarotenoid C (4) showed weak activity against the human breast cancer cell line MDA-MB-231 with IC50 values of 33.3 and 93.8 mu M, respectively.
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| 22. |
- Rekić, Dinko, 1984, et al.
(författare)
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External Validation of the Bilirubin-Atazanavir Nomogram for Assessment of Atazanavir Plasma Exposure in HIV-1-Infected Patients.
- 2013
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Ingår i: The AAPS journal. - : Springer Science and Business Media LLC. - 1550-7416. ; 15:2, s. 308-15
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Tidskriftsartikel (refereegranskat)abstract
- Atazanavir increases plasma bilirubin levels in a concentration-dependent manner. Due to less costly and readily available assays, bilirubin has been proposed as a marker of atazanavir exposure. In this work, a previously developed nomogram for detection of suboptimal atazanavir exposure is validated against external patient populations. The bilirubin nomogram was validated against 311 matching bilirubin and atazanavir samples from 166 HIV-1-infected Norwegian, French, and Italian patients on a ritonavir-boosted regimen. In addition, the nomogram was evaluated in 56 Italian patients on an unboosted regimen. The predictive properties of the nomogram were validated against observed atazanavir plasma concentrations. The use of the nomogram to detect non-adherence was also investigated by simulation. The bilirubin nomogram predicted suboptimal exposure in the patient populations on a ritonavir-boosted regimen with a negative predictive value of 97% (95% CI 95-100). The bilirubin nomogram and monitoring of atazanavir concentrations had similar predictive properties for detecting non-adherence based on simulations. Although both methods performed adequately during a period of non-adherence, they had lower predictive power to detect past non-adherence episodes. Using the bilirubin nomogram for detection of suboptimal atazanavir exposure in patients on a ritonavir-boosted regimen is a rapid and cost-effective alternative to routine measurements of the actual atazanavir exposure in plasma. Its application may be useful in clinical settings if atazanavir concentrations are not available.
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| 23. |
- Ekman, Elisabet, et al.
(författare)
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Awareness among nurses about reporting of adverse drug reactions in Sweden
- 2012
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Ingår i: Drug, Healthcare and Patient Safety. - 1179-1365. ; 4, s. 61-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of this study was to investigate awareness among nurses regarding their new role as reporters of adverse drug reactions in Sweden and factors that may influence reporting by nurses.Methods: In 2007, all nurses were included in the adverse drug reaction reporting scheme in Sweden. A questionnaire was sent to 753 randomly selected nurses in September 2010.Results: Of the 453 (60%) responding nurses, 265 (58%) were aware that nurses were included in the reporting of adverse drug reactions. Sixty-one nurses (14%) stated that they had reported an adverse drug reaction. Fifteen percent (n = 70) of the respondents had received training about reporting of adverse drug reactions. Almost one third of these (n = 21, 30%) had reported an adverse drug reaction on at least one occasion. Among nurses without training, a smaller proportion (n = 40, 11%, P < 0.05) had reported an adverse drug reaction on at least one occasion. The two factors considered most important by nurses for reporting were the severity of the adverse drug reaction and if the reaction was to a newly approved drug. A majority of the nurses (n = 397, 88%) were interested in a training course in pharmacology as part of their ongoing professional development. One third (32%) of all nurses stated that one reason for not reporting a suspected adverse drug reaction was that the physician responsible did not regard the reaction necessary to report.Conclusion: We found that more than half of the study population of nurses in Sweden were aware of their new role as reporters of adverse drug reactions, but few of the responding nurses had reported an adverse drug reaction. Given that training seems to be associated with high reporting frequency, we suggest more training in pharmacovigilance for nurses.
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| 24. |
- Xu, Bo, 1980-
(författare)
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Evolutionary and Pharmacological Studies of NPY and QRFP Receptors
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The neuropeptide Y (NPY) system consists of 3-4 peptides and 4-7 receptors in vertebrates. It has powerful effects on appetite regulation and is involved in many other biological processes including blood pressure regulation, bone formation and anxiety. This thesis describes studies of the evolution of the NPY system by comparison of several vertebrate species and structural studies of the human Y2 receptor, which reduces appetite, to identify amino acid residues involved in peptide-receptor interactions.The NPY system was studied in zebrafish (Danio rerio), western clawed frog (Xenopus tropicalis), and sea lamprey (Petromyzon marinus). The receptors were cloned and functionally expressed and their pharmacological profiles were determined using the native peptides in either binding studies or a signal transduction assay. Some peptide-receptor preferences were observed, indicating functional specialization.A receptor family closely related to the NPY receptors, called the QRFP receptors, was investigated. A QRFP receptor was cloned from amphioxus, Branchistoma floridae, showing that the receptor arose before the origin of the vertebrates. Evolutionary studies demonstrated that the ancestral vertebrate had as many as four QRFP receptors, only one of which remains in mammals today. This correlates with the NPY receptor family, located in the same chromosomal regions, which had seven members in the ancestral vertebrate but only 4-5 in living mammals. Some vertebrates have considerably more complex NPY and QRFP receptor systems than humans and other mammals.Two studies investigated interactions of NPY-family peptides with the human Y2 receptor. Candidate residues, selected based on structural modeling and docking, were mutated to disrupt possible interactions with peptide ligands. The modified receptors were expressed in cultured cells and investigated by measuring binding and functional responses. Several receptor residues were found to influence peptide-receptor interactions, some of which are involved in maintaining receptor structure. In a pilot study, the kinetics of peptide-receptor interaction were found to be very slow, of the order several hours.In conclusion, this thesis clarifies evolutionary relationships for the complex NPY and QRFP peptide-receptor systems and improves the structural models of the human NPY-family receptors, especially Y2. These results will hopefully facilitate drug design for targeting of NPY-family receptors.
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| 25. |
- Ragno, Rino, et al.
(författare)
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Structure-based modeling and target-selectivity prediction
- 2014
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Patent (populärvet., debatt m.m.)abstract
- The present invention provides, inter alia, methods, models, and systems for selecting an effector having specificity for a target molecule. The methods and systems of the present invention involve several steps, including compiling a database containing structural data for a library of molecules and a population of ligands and activity data, establishing structure-based equivalence of sequence elements in the library of molecules, determining likely spatial orientations of population ligands in library molecules, calculating interaction energies for each ligand-molecule pair, generating statistical models that are predictive of sequence elements likely to contribute to a differential effect of ligands on molecules, selecting an effector that is likely to have a desired specificity for the target molecule, experimentally determining activity data for effector-library molecule pairs, and at least once repeating the steps listed above wherein the effector is a member of the population of ligands.
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