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- Andersson, Irene, 1978, et al.
(author)
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Reduced sympathetic responsiveness as well as plasma and tissue noradrenaline concentration in growth hormone transgenic mice
- 2004
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In: Acta Physiol Scand. - 0001-6772. ; 182:4, s. 369-78
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Journal article (peer-reviewed)abstract
- AIMS: Acromegaly [overproduction of growth hormone (GH)] and GH deficiency have both been associated with alterations in autonomic nervous system function. The aim of this study was to investigate autonomic nervous system influence on heart rate (HR) in transgenic mice overexpressing bovine GH (bGH). METHODS: HR and HR variability (HRV) were measured in conscious young (8-13 weeks) and old (5-6 months) female bGH and control mice using telemetry. HR control was studied using antagonists and an agonist of adrenergic and muscarinic receptors. Noradrenaline was measured in plasma, heart and kidney using high performance liquid chromatography. RESULTS: Average 24 h resting HR did not differ between bGH and control mice. After saline injection and after muscarinic blockade with methylscopolamine HR increase was blunted (in old) or absent (in young) bGH mice compared with control mice (P < 0.05). Phenylephrine caused a baroreflex mediated decrease in HR from around 550 to 300-350 beats min(-1), not different between bGH and control mice. Time- and frequency-domain measures of HRV were reduced in old bGH compared with control mice (P < 0.05). Noradrenaline concentrations were reduced by 25-49% in plasma and tissue of bGH compared with control mice (P < 0.05). CONCLUSION: The current study suggests reduced autonomic modulation of HR in bGH transgenic mice. Thus, GH appears to have marked effects on autonomic tone, reducing sympathetic nervous system function possibly via reduced noradrenaline stores.
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| 2. |
- Andreasson, Linnea, et al.
(author)
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Differentiation of induced pluripotent stem cells into definitive endoderm on Activin A-functionalized gradient surfaces
- 2021
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In: Journal of Biotechnology. - : Elsevier BV. - 0168-1656. ; 325:January, s. 173-178
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Journal article (peer-reviewed)abstract
- Activin A plays a central role in the differentiation of stem cells into definitive endoderm, the first step in embryonic development and function development in many organ systems. The aims of this study were to induce controlled and fine-tuned cell differentiation using a gradient nanotechnology and compare this with a classic protocol and to investigate how induced pluripotent stem cells differentiated depending on the gradual increase of Activin A. The density difference was tested by attaching Activin A to a gold nanoparticle gradient for high-precision density continuity. Cells expressed the definitive endoderm markers SRY-box transcription factor 17 and transcription factor GATA-4 to different extents along the gradient, indicating a density-dependent cell response to Activin A. In both the gradient and the classic differentiation setups, the protein expression increased from days 1 to 5, but a significant increase already on day 3 was found only in the gradient-based setup. By utilizing the gradient technology to present the right amount of active biomolecules to cells in vitro, we were able to find an optimal setting for differentiation into definitive endoderm. The use of gradient surfaces for differentiation allows for improvements, such as efficiency and faster differentiation, compared with a classic protocol. © 2020 Elsevier B.V.
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| 3. |
- Bohlooly-Yeganeh, Mohammad, 1966, et al.
(author)
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Selective cerebral overexpression of growth hormone alters cardiac function, morphology, energy metabolism and catecholamines in transgenic mice
- 2005
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In: Growth hormone & IGF research. - : Elsevier BV. - 1096-6374. ; 15:2, s. 148-55
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Journal article (peer-reviewed)abstract
- BACKGROUND: Growth hormone (GH) has important regulatory effects on cardiac morphology and function both during normal development as well as in pathophysiological settings such as myocardial infarction (MI) and congestive heart failure (CHF). In order to investigate in more detail the interaction between GH and sympathetic nervous system (SNS) system we studied the effects of selective cerebral GH overexpression on myocardial content of catecholamines, myocardial and brain energy metabolism as well as on cardiac function during resting and stress conditions in a transgenic mouse model. METHODS: Transgenic mice with selective bovine GH overexpression under control of glial fibrillary acidic protein promoter in the brain (GFAP-bGH, n=15) were created and compared to genetically matched non-transgenic mates (Control, n=15). Cardiac morphology and function were evaluated in vivo using transthoracic echocardiography during resting and stress conditions induced pharmacologically by dopamine (D) and isoprotenolol (ISO). Myocardial and brain energy metabolism were evaluated non-invasively using in vivo volume-selective phosphorus magnetic resonance spectroscopy ((31)P MRS). Myocardial content of catecholamines was analyzed by means of HPLC. RESULTS: Compared to the C animals, the GFAP-bGH mice have showed several differences in the cardiac phenotype. Systolic (fractional shortening) and diastolic function (E/A wave ratio of mitral flow) was disturbed in the GFAP-bGH mice (both p<0.05). During the dopamine stress, there was chronotropic insufficiency in the GFAP-bGH group (p<0.01) while no difference was observed in response to isoprotenolol. Left ventricular dimensions were increased in GFAP-bGH mice (p<0.05). There was a tendency for higher body weight in GFAP-bGH compared to the control group (p=0.06) while no difference was observed in heart weight and brain weight when normalized for body weight. Myocardial content of noradrenaline was lower in the GFAP-bGH group (p<0.05). PCr/ATP ratio was higher (p<0.05) in the brain and lower in the heart (p<0.05) in the GFAP-bGH mice. CONCLUSIONS: Selective cerebral overexpression of GH results in alterations of cardiac function, morphology and metabolism in transgenic mice. Decreased myocardial content of catecholamines in the GFAP-bGH mice suggests central interaction between GH and sympathetic nervous system.
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| 4. |
- Evenbratt, H., et al.
(author)
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Insights into the present and future of cartilage regeneration and joint repair
- 2022
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In: Cell Regeneration. - : Springer Science and Business Media LLC. - 2045-9769. ; 11:1
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Research review (peer-reviewed)abstract
- Knee osteoarthritis is the most common joint disease. It causes pain and suffering for affected patients and is the source of major economic costs for healthcare systems. Despite ongoing research, there is a lack of knowledge regarding disease mechanisms, biomarkers, and possible cures. Current treatments do not fulfill patients’ long-term needs, and it often requires invasive surgical procedures with subsequent long periods of rehabilitation. Researchers and companies worldwide are working to find a suitable cell source to engineer or regenerate a functional and healthy articular cartilage tissue to implant in the damaged area. Potential cell sources to accomplish this goal include embryonic stem cells, mesenchymal stem cells, or induced pluripotent stem cells. The differentiation of stem cells into different tissue types is complex, and a suitable concentration range of specific growth factors is vital. The cellular microenvironment during early embryonic development provides crucial information regarding concentrations of signaling molecules and morphogen gradients as these are essential inducers for tissue development. Thus, morphogen gradients implemented in developmental protocols aimed to engineer functional cartilage tissue can potentially generate cells comparable to those within native cartilage. In this review, we have summarized the problems with current treatments, potential cell sources for cell therapy, reviewed the progress of new treatments within the regenerative cartilage field, and highlighted the importance of cell quality, characterization assays, and chemically defined protocols.
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| 9. |
- Ågren, Greta, et al.
(author)
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Allometric or induced-effects?
- 2007
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In: Forensic Science International. - : Elsevier BV. - 0379-0738 .- 1872-6283. ; 169, s. S7-S7
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Research review (other academic/artistic)abstract
- The change in size of peripheral organs is one indicator used to describe effects of an intervention in experimental studies, or in observational studies.It is common practice to express size in terms of organ-weight in relation to bodyweight. When effects on size as such are looked for, this can be misleading. The particular treatment may affect the weight of the organ, the total weight of body at the time for sacrifice and dissections, or affect the organ size and bodyweight. ‘Which’ bodyweight is used for reference will affect the results obtained.To illustrate this point the results are presented of a study on the effects on organ-weight of an anabolic androgenic steroid: Nandrolone decanoate. Twenty-four (330–470 g) male Wistar rats (Taconic M&B, Ry, Denmark) were randomly divided in four treatment groups of six rats. The rats in each group received injections of either the vehicle (Arachidis oleum) or Nandrolone decanoate in one of three doses (1, 5 or 10 mg/kg). The rats received a daily injection subcutaneously (s.c.) for 19 days. The rats were sacrificed on the day following the last injections. The rats were weighed at the onset and end of the study.The poster presents the weight of a selection of peripheral organs relative to individual pre-experimental and post-experimental weight, and relative to the dose given and growth over the treatment-period. The implications in each case are discussed in terms of effects on each target of the drug-treatment.
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