| 61. |
- Wallén-Mackenzie, Åsa, et al.
(författare)
-
Restricted cortical and amygdaloid removal of vesicular glutamate transporter 2 in preadolescent mice impacts dopaminergic activity and neuronal circuitry of higher brain function.
- 2009
-
Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401 .- 0270-6474. ; 29:7, s. 2238-51
-
Tidskriftsartikel (refereegranskat)abstract
- A major challenge in neuroscience is to resolve the connection between gene functionality, neuronal circuits, and behavior. Most, if not all, neuronal circuits of the adult brain contain a glutamatergic component, the nature of which has been difficult to assess because of the vast cellular abundance of glutamate. In this study, we wanted to determine the role of a restricted subpopulation of glutamatergic neurons within the forebrain, the Vglut2-expressing neurons, in neuronal circuitry of higher brain function. Vglut2 expression was selectively deleted in the cortex, hippocampus, and amygdala of preadolescent mice, which resulted in increased locomotor activity, altered social dominance and risk assessment, decreased sensorimotor gating, and impaired long-term spatial memory. Presynaptic VGLUT2-positive terminals were lost in the cortex, striatum, nucleus accumbens, and hippocampus, and a downstream effect on dopamine binding site availability in the striatum was evident. A connection between the induced late-onset, chronic reduction of glutamatergic neurotransmission and dopamine signaling within the circuitry was further substantiated by a partial attenuation of the deficits in sensorimotor gating by the dopamine-stabilizing antipsychotic drug aripiprazole and an increased sensitivity to amphetamine. Somewhat surprisingly, given the restricted expression of Vglut2 in regions responsible for higher brain function, our analyses show that VGLUT2-mediated neurotransmission is required for certain aspects of cognitive, emotional, and social behavior. The present study provides support for the existence of a neurocircuitry that connects changes in VGLUT2-mediated neurotransmission to alterations in the dopaminergic system with schizophrenia-like behavioral deficits as a major outcome.
|
|
| 62. |
- Insulander Björk, Klara, 1982, et al.
(författare)
-
Experimental determination of concentration factors of Mn, Zn and I in the phytoplankton species Phaeodactylum Tricornutum
- 2023
-
Ingår i: Journal of Environmental Radioactivity. - : Elsevier BV. - 0265-931X .- 1879-1700. ; 261
-
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.
|
|
| 63. |
- Albofetileh, Mehdi, et al.
(författare)
-
Seaweed Proteins as a Source of Bioactive Peptides
- 2021
-
Ingår i: Current Pharmaceutical Design. - : Bentham Science Publishers Ltd.. - 1873-4286 .- 1381-6128. ; 27:11, s. 1342 -1352
-
Forskningsöversikt (refereegranskat)abstract
- Seaweeds have gained great attention as a vegetarian and sustainable marine source of protein which do not need irrigation, arable land and fertilization. Besides, seaweeds are considered as an untapped resource for discovering bioactive compounds with health benefits where bioactive peptides have shown outstanding potential. This review provides a detailed overview of available scientific knowledge on production methods, bioactivity and application of peptides from seaweed proteins. The emphasize is on the effects form seaweed varieties and peptide production condition on the bioactivity of the peptides and their potential health benefits. Bioactive properties of seaweed peptides including antioxidant, antihypertensive, antidiabetic, anti-inflammatory, anticancer activities and other potential health benefits have been discussed. It also covers current challenges and required future research and innovations for the successful application of seaweeds proteins as a sustainable source of bioactive peptides. Effects from seasonal variation of seaweed composition on the bioactivity of their peptides, difficulties in the extraction of proteins from seaweed complex structure, scalability and reproducibility of the developed methods for the production of bioactive peptides, the safety of the peptides are examples of highlighted challenges. Further studies on the bioavailability of the seaweed bioactive peptides and validation of the results in animal models and human trials are needed before their application as functional foods or pharmaceutical ingredients.
|
|
| 64. |
- Asghar, Afshan, et al.
(författare)
-
"Ficus johannis Boiss. leaves ethanolic extract ameliorate streptozotocin-induced diabetes in rats by upregulating the expressions of GCK, GLUT4, and IGF and downregulating G6P"
- 2023
-
Ingår i: Environmental Science and Pollution Research. - : Springer Nature. - 0944-1344 .- 1614-7499. ; 30:17, s. 49108-49124
-
Tidskriftsartikel (refereegranskat)abstract
- The leaves of Ficus johannis Boiss (F. johannis), commonly known as Fig tree, Anjir, and Teen, are used by the folk medicinal practitioners in Iran for controlling hyperglycemia in diabetic patients. This study investigated the pharmacological basis for antidiabetic effect of the ethanolic extract of F. johannis leaves using in vitro and in vivo experimental models. Qualitative screening of phytochemicals, estimation of total phenolic and flavonoid contents, and in vitro antioxidant and α-amylase inhibition assays were performed. Moreover, the High-performance liquid chromatography (HPLC) quantification, acute toxicity, glucose tolerance, and in vivo antidiabetic effect along with the evaluation of gene expressions involved in diabetes mellitus were carried out. Significant quantities of phenolic (71.208 ± 2.89 mgg−1 GAE) and flavonoid (26.38 ± 3.53 mgg−1 QE) were present. Inhibitory concentration (IC50) of the plant extract exhibited an excellent in vitro antioxidant (IC50 = 33.81 µg/mL) and α-amylase (IC50 = 12.18 µg/mL) inhibitory potential. The HPLC analysis confirmed the gallic acid (257.79 mgg−1) as main constituent of the extract followed by kaempferol (22.86 mgg−1), myricetin (0.16 mgg−1), and quercetin (3.22 mgg−1). Ethanolic extract displayed glucose tolerance in normo-glycemic rats. Streptozotocin-induced hyperglycemia declined dose dependently in the extract treated rats with improvement in lipid profile and liver and renal function biomarkers. The F. johannis-treated groups showed an increase in mRNA expressions of glucose transporter 4 (GLUT-4), glucokinase, insulin growth like factor 1 and peroxisomal proliferator activating receptor gamma in pancreas. However, the Glucose-6-phosphatase was downregulated. Present study suggests that the ethanolic extract of F. johannis leaves demonstrates a good anti-diabetic profile by improving insulin sensitivity, GLUT-4 translocation, and carbohydrate metabolism while inhibiting lipogenesis.
|
|
| 65. |
- Gabrielsson, Johan
(författare)
-
Dose-response-time data analysis involving nonlinear dynamics, feedback and delay
- 2014
-
Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 59, s. 36-48
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 66. |
- Gabrielsson, Johan
(författare)
-
Mixture dynamics: Dual action of inhibition and stimulation
- 2013
-
Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 50, s. 215-226
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 67. |
- Gennemark, Peter, 1974, et al.
(författare)
-
Modeling energy intake by adding homeostatic feedback and drug intervention
- 2015
-
Ingår i: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 42:1, s. 79-96
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 68. |
- Hansson, Elisabeth, 1955, et al.
(författare)
-
Therapeutic innovation: Inflammatory-reactive astrocytes as targets of inflammation
- 2016
-
Ingår i: IBRO Reports. - : Elsevier BV. - 2451-8301. ; 1, s. 1-9
-
Tidskriftsartikel (refereegranskat)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)
|
|
| 69. |
- Holmbäck, Jan, et al.
(författare)
-
Preclinical development of sodium fusidate antibiotic cutaneous spray based on water-free lipid formulation system
- 2022
-
Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 176
-
Tidskriftsartikel (refereegranskat)abstract
- Topical antibiotics are a key component in the management of mild to moderate skin and soft tissue infections. There are, however, concerns about the emerging bacterial resistance against topical antibacterial agents such as fusidic acid, due to the prolonged treatment period of its marketed dosage forms. Improving the efficacy of topical formulations could potentially shorten the treatment period and avoid the resistance growth. To provide a more effective drug delivery, a water-free lipid-based formulation system (AKVANO (R)) which can be applied by spraying, has been developed. In the current paper, different formulations containing sodium fusidate were evaluated for their in vitro skin permeability using artificial skin mimicking membranes and antibacterial properties using ex vivo and in vivo skin wound infection models. The novel formulations containing sodium fusidate showed a much higher skin permeation (up to 60% of nominal amount) than the commercially available Fucidin (R) cream (3%). These formulations also gave a significantly stronger antibacterial effect than Fucidin cream showing a clear dose-response relationship for the sodium fusidate content. A spray product based on the described formulation technology would therefore require a shorter treatment time and thereby lower the risk for the development of bacterial resistance. Spray administration of these formulations provides an even layer on the skin surface from which the solvent quickly evaporates and thereby facilitates a non-touch application where no rubbing is required.
|
|
| 70. |
|
|
