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| 2. |
- Landberg, Rikard, 1981, et al.
(author)
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Avenanthramides as lipoxygenase inhibitors
- 2020
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In: Heliyon. - : Elsevier BV. - 2405-8440. ; 6:6
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Journal article (peer-reviewed)abstract
- Avenanthramides (AVAs) present in oats are amides of anthranilic and cinnamic acids. AVAs are potent antioxidants and have anti-inflammatory properties. There are various potential mechanisms for their anti-inflammatory effects, including inhibition of lipoxygenases (LOX), which catalyse oxygenation of polyunsaturated fatty acids into potent signal molecules involved in inflammatory processes. In this study, AVAs were screened for LOX inhibition in vitro and structure-activity relationships were examined. Twelve different AVAs at 0.6 mM were tested as LOX inhibitors. The corresponding free cinnamic acids, the AVA analogue Tranilast® and the known LOX inhibitor trans-resveratrol were included for comparison. It was found that AVAs comprising caffeic or sinapic acid exhibited significant lipoxygenase inhibition (60–90%) (P < 0.05), whereas low or no inhibition was observed with AVAs containing p-coumaric or ferulic acid. No difference in inhibition was seen on comparing AVAs with their free corresponding cinnamic acids, which implies that the anthranilic acid part of the avenanthramide molecule does not affect inhibition. Trans-resveratrol showed inhibition, whereas no inhibition was seen for Tranilast® at the concentrations used in this study. This study suggests that aventahtramides comprising caffeic acid or sinapic acid partly exert their antioxidant and anti-inflammatory effects via lipoxygenase inhibition.
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| 3. |
- Ronquist, K Göran, et al.
(author)
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Prostasomes from four different species are able to produce extracellular adenosine triphosphate (ATP)
- 2013
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In: Biochimica et Biophysica Acta - General Subjects. - : Elsevier BV. - 0304-4165 .- 1872-8006. ; 1830:10, s. 4604-4610
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Journal article (peer-reviewed)abstract
- BACKGROUND:Prostasomes are extracellular vesicles. Intracellularly they are enclosed by another larger vesicle, a so called "storage vesicle" equivalent to a multivesicular body of late endosomal origin. Prostasomes in their extracellular context are thought to play a crucial role in fertilization.METHODS:Prostasomes were purified according to a well worked-out schedule from seminal plasmas obtained from human, canine, equine and bovine species. The various prostasomes were subjected to SDS-PAGE separation and protein banding patterns were compared. To gain knowledge of the prostasomal protein systems pertaining to prostasomes of four different species proteins were analyzed using a proteomic approach. An in vitro assay was employed to demonstrate ATP formation by prostasomes of different species.RESULTS:The SDS-PAGE banding pattern of prostasomes from the four species revealed a richly faceted picture with most protein bands within the molecular weight range of 10-150kDa. Some protein bands seemed to be concordant among species although differently expressed and the number of protein bands of dog prostasomes seemed to be distinctly fewer. Special emphasis was put on proteins involved in energy metabolic turnover. Prostasomes from all four species were able to form extracellular adenosine triphosphate (ATP). ATP formation was balanced by ATPase activity linked to the four types of prostasomes.CONCLUSION:These potencies of a possession of functional ATP-forming enzymes by different prostasome types should be regarded against the knowledge of ATP having a profound effect on cell responses and now explicitly on the success of the sperm cell to fertilize the ovum.GENERAL SIGNIFICANCE:This study unravels energy metabolic relationships of prostasomes from four different species.
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| 4. |
- Gabrielsson, Johan
(author)
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Dose-response-time data analysis involving nonlinear dynamics, feedback and delay
- 2014
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In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 59, s. 36-48
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Journal article (peer-reviewed)abstract
- This paper offers dose-response-time data analysis of four different case studies where the pharmacological response (neuronal ACh-release, tail-flick response, locomotor activity, NEFA) was modelled by a biophase-driven turnover model. The analysis uses a mathematical/analytical perspective in which analytic properties of the models involved are exploited in order to address the dual challenge of extracting information from these time-series about (i) the biophase kinetics following different routes of administration and (ii) pharmacodynamic issues such as transduction, saturation, and adaptation, and more specifically, parameter identifiability, such as correct estimation of potency (SD50 or ID50). It is shown how many of these estimates can be obtained by analytical means, giving considerable insight in the dynamics involved. (C) 2014 Elsevier B.V. All rights reserved.
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| 5. |
- Gabrielsson, Johan
(author)
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Mixture dynamics: Dual action of inhibition and stimulation
- 2013
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In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 50, s. 215-226
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Journal article (peer-reviewed)abstract
- The impact of a drug, or of multiple drugs, on different receptors usually results in a combination of responses. They may be either opposing or reinforcing one another and can lead to complex response versus drug-concentration relations. In this paper, complexity and synergy of multiple drug actions are studied on the basis of four data sets: two involving opposing actions and two resulting from synergistic actions. It is shown that turnover models can be successfully fitted to these data, offer a mechanism for dissecting complex response versus drug-concentration curves, for understanding and quantifying amplification of dual drug actions and elucidate the role of potencies and other parameters related to the different drugs. (C) 2013 Elsevier B.V. All rights reserved.
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| 6. |
- Gennemark, Peter, 1974, et al.
(author)
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Modeling energy intake by adding homeostatic feedback and drug intervention
- 2015
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In: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 42:1, s. 79-96
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Journal article (peer-reviewed)abstract
- Energy intake (EI) is a pivotal biomarker used in quantification approaches to metabolic disease processes such as obesity, diabetes, and growth disorders. Eating behavior is however under both short-term and long-term control. This control system manifests itself as tolerance and rebound phenomena in EI, when challenged by drug treatment or diet restriction. The paper describes a model with the capability to capture physiological counter-regulatory feedback actions triggered by energy imbalances. This feedback is general as it handles tolerance to both increases and decreases in EI, and works in both acute and chronic settings. A drug mechanism function inhibits (or stimulates) EI. The deviation of EI relative to a reference level (set-point) serves as input to a non-linear appetite control signal which in turn impacts EI in parallel to the drug intervention. Three examples demonstrate the potential usefulness of the model in both acute and chronic dosing situations. The model shifts the predicted concentration-response relationship rightwardly at lower concentrations, in contrast to models that do not handle functional adaptation. A fourth example further shows that the model may qualitatively explain differences in rate and extent of adaptation in observed EI and its concomitants in both rodents and humans.
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| 7. |
- Hansson, Elisabeth, 1955, et al.
(author)
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Therapeutic innovation: Inflammatory-reactive astrocytes as targets of inflammation
- 2016
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In: IBRO Reports. - : Elsevier BV. - 2451-8301. ; 1, s. 1-9
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Journal article (peer-reviewed)abstract
- This study aimed to test pharmaceutical compounds targeting astrocytes showing inflammatory dysregulation. The primary rat brain cultures were treated with different batches of serum with or without microglia added to make the cells inflammatory-reactive. Lipopolysaccharide (LPS) and tryptase were used as inflammatory inducers. Expression levels of Toll-like receptor 4 (TLR4), Na+/K+-ATPase, and matrix metalloprotease-13 (MMP-13), as well as actin filament organization, pro-inflammatory cytokines, and intracellular Ca2+ release, were evaluated. LPS combined with tryptase upregulated TLR4 expression, whereas Na+/K+-ATPase expression was downregulated, ATP-evoked Ca2+ transients were increased, actin filaments were reorganized and ring structures instead of stress fibers were observed. Other aims of the study were to prevent astrocytes from becoming inflammatory-reactive and to restore inflammatory dysregulated cellular changes. A combination of the μ-opioid antagonist (−)-naloxone in ultra-low concentrations, the non-addictive μ-opioid agonist (−)-linalool, and the anti-epileptic agent levetiracetam was examined. The results indicated that this drug cocktail prevented the LPS- and tryptase-induced inflammatory dysregulation. The drug cocktail could also restore the LPS- and tryptase-treated cells back to a normal physiological level in terms of the analyzed parameters. © 2016 The Author(s)
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| 8. |
- Chapman, Henry N, et al.
(author)
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Femtosecond X-ray protein nanocrystallography.
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 470:7332, s. 73-7
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Journal article (peer-reviewed)abstract
- X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (∼200 nm to 2 μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.
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| 9. |
- Engell, Maria Terese, et al.
(author)
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Postural changes and their effects in elite riders when actively influencing the horse versus sitting passively at trot
- 2016
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In: Comparative Exercise Physiology. - 1755-2540 .- 1755-2559. ; 12, s. 27-33
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Journal article (peer-reviewed)abstract
- The objectives were to compare sagittal plane posture of the pelvis, trunk and head of elite dressage riders when they ride actively to train the horse versus sitting passively and following the horses' movements at trot, and to evaluate the effects of these changes in rider posture on load distribution on the horse's back. Synchronised motion capture and saddle mat data of seven elite dressage riders were used to measure minimal and maximal angles and range of motion (ROM) for the pelvic, trunk and head segments, the angle between pelvis and trunk segments, phase-shift between pitching motions of pelvis and trunk, and pelvic translation relative to the saddle. Non-parametric statistical tests compared variables between the two rider postures. In the passive rider posture the pelvis, trunk and head showed two pitching cycles per stride. Maximal posterior and anterior pelvic rotation occurred, respectively, early and late in the horse's diagonal stance phase. Compared with pelvic movements, trunk movements were slightly delayed and head movements were out-of-phase. In the active rider posture the pelvis and trunk pitched further posteriorly throughout the stride. Most of the riders showed similar sagittal plane movements of the axial body segments but with some notable individual variations.
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| 10. |
- Lindberg, Frida A, et al.
(author)
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Behavioral profiling of SLC38A10 knockout mice using the multivariate concentric square field™ test
- 2022
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In: Frontiers in Behavioral Neuroscience. - : Frontiers Media S.A.. - 1662-5153 .- 1662-5153. ; 16
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Journal article (peer-reviewed)abstract
- Introduction: SLC38A10 is a gene that encodes the SLC38A10 protein, also known as SNAT10. The SLC38 family is evolutionary old, and SLC38A10 is one of the oldest members of the family. It is ubiquitously expressed, and its substrates are glutamine, glutamate, alanine, aspartate, and serine. However, little is known about its biological importance.Methods: In the current study, an SLC38A10 knockout mouse was run in the multivariate concentric square field (TM) (MCSF) test. The MCSF test gives the mouse a choice of areas to explore; sheltered areas, elevated and illuminated areas, or open spaces, and a behavioral profile is obtained. The multivariate data obtained were analyzed (i) for each parameter, (ii) parameters grouped into functional categories, and (iii) with a principal component analysis.Results: In the trend analysis, knockout mice had a decreased exploratory behavior compared to controls but did not show a distinct grouping in the principal component analysis.Discussion: There was not a pronounced difference in the behavioral profile in SLC38A10 knockout mice compared to their wild-type controls, although subtle alterations in zones associated with exploratory behavior and risk assessment in female and male knockout mice, respectively, could be observed. These results imply that a loss of function of the SLC38A10 protein in mice does not drastically alter behavior in the MSCF test.
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