| 31. |
- Nilsson, Avlant, 1985, et al.
(författare)
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Complex I is bypassed during high intensity exercise
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Human muscles are tailored towards ATP synthesis. When exercising at high work rates muscles convert glucose to lactate, which is less nutrient efficient than respiration. There is hence a trade-off between endurance and power. Metabolic models have been developed to study how limited catalytic capacity of enzymes affects ATP synthesis. Here we integrate an enzyme-constrained metabolic model with proteomics data from muscle fibers. We find that ATP synthesis is constrained by several enzymes. A metabolic bypass of mitochondrial complex I is found to increase the ATP synthesis rate per gram of protein compared to full respiration. To test if this metabolic mode occurs in vivo, we conduct a high resolved incremental exercise tests for five subjects. Their gas exchange at different work rates is accurately reproduced by a whole-body metabolic model incorporating complex I bypass. The study therefore shows how proteome allocation influences metabolism during high intensity exercise.
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| 32. |
- Björn, Camilla, et al.
(författare)
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Anti-infective efficacy of the lactoferrin-derived antimicrobial peptide HLR1r
- 2016
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 81, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides (AMPs) have emerged as a new class of drug candidates for the treatment of infectious diseases. Here we describe a novel AMP, HLR1r, which is structurally derived from the human milk protein lactoferrin and demonstrates a broad spectrum microbicidal action in vitro. The minimum concentration of HLR1r needed for killing >= 99% of microorganisms in vitro, was in the range of 3-50 mu g/ml for common Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and for the yeast Candida albicans, when assessed in diluted brain-heart infusion medium. We found that HLR1r also possesses anti-inflammatory properties as evidenced by inhibition of tumor necrosis factor alpha (TNF-alpha) secretion from human monocyte-derived macrophages and by repression of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) secretion from human mesothelial cells, without any cytotoxic effect observed at the concentration range tested (up to 400 mu g/ml). HLR1r demonstrated pronounced anti-infectious effect in in vivo experimental models of cutaneous candidiasis in mice and of excision wounds infected with MRSA in rats as well as in an ex vivo model of pig skin infected with S. aureus. In conclusion, HLR1r may constitute a new therapeutic alternative for local treatment of skin infections. (C) 2016 Elsevier Inc. All rights reserved.
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| 33. |
- Hellström, Lina, et al.
(författare)
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Impact of the Lund Integrated Medicines Management (LIMM) model on medication appropriateness and drug-related hospital revisits.
- 2011
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 67:7, s. 741-752
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo examine the impact of systematic medication reconciliations when admitted to hospital, and medication review while in hospital, on the number of inappropriate medications and unscheduled drug-related hospital revisits in elderly patients.MethodsA prospective, controlled study in 210 patients, aged 65 years or older, who were admitted to one of three internal medicine wards at a University Hospital in Sweden. Patients received either standard care or care according to the Lund Integrated Medicines Management (LIMM) model. A multi-professional team, including a clinical pharmacist, provided medication reconciliations on admission and medication reviews during the hospital stay for the LIMM group. Blinded reviewers evaluated the appropriateness of the prescribing (using the Medication Appropriateness Index) on admission and discharge, and assessed the probability that a drug-related problem was the reason for any patient readmitted to hospital or visiting the emergency department within three months of discharge (using WHO causality criteria).ResultsThere was a greater decrease in the number of inappropriate drugs in the intervention group than in the control group for both the intention-to-treat population (51% [95% CI 43-58%] versus 39% [95% CI 30-48%], p=0.0446) and the per-protocol population (60% [95% CI 51-67%] versus 44% [95% CI 34-52 %], p=0.0106). There were 6 revisits to hospital in the intervention group which were judged as ‘possibly, probably or certainly drug-related’, compared with 12 in the control group (p=0.0469).ConclusionIn this study, medication reconciliation and reviews provided by a clinical pharmacist in a multi-professional team significantly reduced the number of inappropriate drugs and unscheduled drug-related hospital revisits for elderly patients.
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| 34. |
- van West, Dirk, et al.
(författare)
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Glucocorticoid receptor gene-based SNP analysis in patients with recurrent major depression
- 2006
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Ingår i: Neuropsychopharmacology. - : Nature Publishing Group. - 0893-133X .- 1740-634X. ; 31:3, s. 620-627
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Tidskriftsartikel (refereegranskat)abstract
- Dysregulation of the hypothalamic-pituitary-adrenal axis, one of the stress-response systems, is one of the key neurobiological features of major depression (MDD). Data supporting the notion that glucocorticoid-mediated feedback inhibition is impaired in MDD come from a multitude of studies demonstrating nonsuppression of cortisol secretion following administration of the synthetic glucocorticoid dexamethasone. We examined whether genetic variations in the glucocorticoid receptor gene (Nuclear Receptor Subfamily 3, Group C, Member 1; NR3C1) could be associated with increased susceptibility for MDD using a whole gene-based association analysis of single nucleotide polymorphisms (SNPs). Four SNPs were identified in NR3C1 and genotyped in two well-diagnosed samples of patients with MDD ascertained in Belgium and northern Sweden, and matched control samples. In total, 314 MDD patients and 354 control individuals were included in the study. In the Belgian sample, we observed significant allele (p=0.02) and genotype (p=0.02) association with an SNP in the promoter region (NR3C1-1); in the Swedish sample, we observed significant allele (p=0.02) and genotype (p=0.02) association with the R23K SNP. The haplotype association studies showed modest evidence for an involvement of the 5' region of the NR3C1 gene in the genetic vulnerability for MDD. This study suggests that polymorphisms in the 5' region of the NR3C1 gene may play a role in the genetic vulnerability for MDD.
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| 35. |
- Sjöberg, Rickard L, et al.
(författare)
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Development of depression: sex and the interaction between environment and a promoter polymorphism of the serotonin transporter gene
- 2006
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Ingår i: International Journal of Neuropsychopharmacology. - Uppsala Univ, Cent Hosp Vasteras, Clin Res Ctr, S-72189 Vasteras, Sweden. Univ Uppsala, Pharmacol Unit, Dept Neurosci, Uppsala, Sweden. : CAMBRIDGE UNIV PRESS. - 1461-1457 .- 1469-5111. ; 9:4, s. 443-449
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has demonstrated that a polymorphism in the serotonin transporter gene (5-HTTLPR) and adverse psychosocial circumstances interact to predict depression. The purpose of the present study was to explore the extent to which sex modulates these effects. Eighty-one boys and 119 girls (16-19 years old) were interviewed about psychosocial background variables and genotyped for the 5-HTT promoter polymorphism. There were two main results. First, boys and girls carrying the short 5-HTTLPR allele react to different kinds of environmental factors. Whereas males were affected by living in public housing rather than in own owned homes and by living with separated parents, females were affected by traumatic conflicts within the family. Second, the responses of males and females carrying the short 5-HTTLPR allele to environmental stress factors go in opposite directions. Thus, whereas females tend to develop depressive symptoms, males seem to be protected from depression. The results suggest that both the molecular and the psychosocial mechanisms underlying depression may differ between boys and girls.
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| 36. |
- 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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| 37. |
- Mabeyo, P. E., et al.
(författare)
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Selenium Accumulating Leafy Vegetables Are a Potential Source of Functional Foods
- 2015
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Ingår i: International Journal of Food Science. - : Hindawi Limited. - 2356-7015 .- 2314-5765. ; 2015
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Tidskriftsartikel (refereegranskat)abstract
- Selenium deficiency in humans has been associated with various diseases, the risks of which can be reduced through dietary supplementation. Selenium accumulating plants may provide a beneficial nutrient for avoiding such illnesses. Thus, leafy vegetables such as Amaranthus hybridus, Amaranthus sp., Cucurbita maxima, Ipomoea batatas, Solanum villosum, Solanum scabrum, and Vigna unguiculata were explored for their capabilities to accumulate selenium when grown on selenium enriched soil and for use as a potential source of selenium enriched functional foods. Their selenium contents were determined by spectrophotometry using the complex of 3,3′-diaminobenzidine hydrochloride (DABH) as a chromogen. The mean concentrations in the leaves were found to range from to μg/g dry weight (DW), with C. maxima accumulating the most selenium. In stems, the accumulated selenium content ranged from μg/g in Amaranthus sp. to μg/g DW in C. maxima and was hence significantly different (). The cancer cell line MDA-MB-231 was used in cytotoxicity assays to determine the anticancer potential of these extracts. With exception of S. scabrum and S. villosum, no cytotoxicity was detected for the selenium enriched vegetable extracts up to 100μg/mL concentration. Hence, following careful evaluation the studied vegetables may be considered as selenium enriched functional foods.
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| 38. |
- Makungu, Marco, et al.
(författare)
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Pterocarpans and isoflavones from the roots of Millettia micans and of Millettia dura
- 2016
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Ingår i: Advances in Drug Discovery and Development. ; 1:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- From the CH2Cl2/CH3OH (1:1) extract of the root bark of Millettia micans, a new pterocarpan, (6aR,11aR)-7,8,9-trimethoxy-3-hydroxypterocarpan (1), named micanspterocarpan, was isolated. Similarinvestigation of the CH2Cl2/CH3OH (1:1) extract of the root bark of Millettia dura gave a further new pterocarpan,3-O-prenylmaackiain (2) along with six known isoflavones (3-8) and a chalcone (9). All purifiedcompounds were identified by NMR and MS, and the absolute configuration of 1 was established by quantumchemical CD calculation. The isolated constituents, calopogonium isoflavone B (3) and isoerythrin A-4'-(3-methylbut-2-enyl) ether (4) showed marginal activities against the 3D7 and the Dd2 strains of Plasmodiumfalciparum (70-90% inhibition at 40 M). Maximaisoflavone B (5) and 7,2'-dimethoxy-4',5'-methylenedioxyisoflavone (7) were weakly cytotoxic (IC50 153.5 and 174.1 uM, respectively) against theMDB-MB-231 human breast cancer cell line. None of the tested compounds showed toxicity against theHEK-293 human embryonic kidney cell line at 40 uM.
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| 39. |
- 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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| 40. |
- Nyandoro, Stephen S., 1975, et al.
(författare)
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Polyoxygenated Cyclohexenes and Other Constituents of Cleistochlamys kirkii Leaves
- 2017
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Ingår i: Journal of natural products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 80:1, s. 114-125
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Tidskriftsartikel (refereegranskat)abstract
- Thirteen new metabolites, including the polyoxygenated cyclohexene derivatives cleistodiendiol (1), cleistodienol B (3), cleistenechlorohydrins A (4) and B (5), cleistenediols A–F (6–11), cleistenonal (12), and the butenolide cleistanolate (13), 2,5-dihydroxybenzyl benzoate (cleistophenolide, 14), and eight known compounds (2, 15–21) were isolated from a MeOH extract of the leaves of Cleistochlamys kirkii. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of compounds 1, 17, and 19 were established by single-crystal X-ray diffraction. The configuration of the exocyclic double bond of compound 2 was revised based on comparison of its NMR spectroscopic features and optical rotation to those of 1, for which the configuration was determined by X-ray diffraction. Observation of the co-occurrence of cyclohexenoids and heptenolides in C. kirkii is of biogenetic and chemotaxonomic significance. Some of the isolated compounds showed activity against Plasmodium falciparum (3D7, Dd2), with IC50 values of 0.2–40 μM, and against HEK293 mammalian cells (IC50 2.7–3.6 μM). While the crude extract was inactive at 100 μg/mL against the MDA-MB-231 triple-negative breast cancer cell line, some of its isolated constituents demonstrated cytotoxic activity with IC50 values ranging from 0.03–8.2 μM. Compound 1 showed the most potent antiplasmodial (IC50 0.2 μM) and cytotoxic (IC50 0.03 μM, MDA-MB-231 cell line) activities. None of the compounds investigated exhibited translational inhibitory activity in vitro at 20 μM.
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