| 1. |
- Arino, Hiroshi, et al.
(författare)
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Implantation of Schwann cells in rat tendon autografts as a model for peripheral nerve repair: Long term effects on functional recovery
- 2008
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 1651-2073 .- 0284-4311. ; 42:6, s. 281-285
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Tidskriftsartikel (refereegranskat)abstract
- Cultured Schwann cells in tendon autografts for nerve repair improve the early phase of nerve regeneration in rat sciatic nerves as judged by the rate of axonal outgrowth. We tested the long-term effects on functional recovery using measurements of muscle force, the number of axons and myelination, using morphometry. In addition, we recorded wet weight of the gastrocnemius muscle. Schwann cell cultures were prepared from predegenerated nerves. Ten and 15mm defects in rat sciatic nerves were bridged using bilateral tendon autografts with Schwann cell-seeded tendon autografts on one side, and untreated tendon autografts on the other. Animals were evaluated at six and 12 weeks, respectively. At six weeks, myelination, as judged by G-ratio (ratio of axonal diameter to diameter of nerve fibres), was significantly increased in tendon autografts pretreated with Schwann cells in 10mm defects. No such difference was seen in the 15 mmdefects. We found no difference in functional recovery, other morphometric variables, or muscle weight between the two grafts. We conclude that early effects on nerve regeneration using transplantation of cultured Schwann cells in rat sciatic nerves are temporary. Other strategies are necessary to obtain lasting effects on functional recovery.
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| 6. |
- Brandt, Jerker
(författare)
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Innovation och design : teori och praktik. (Innovation and design - theory and practice)
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Society needs irmovators and entrepreneurs. Therefore new forms of education and training of engineers in product determination, product development and product innovation are needed. The aim of this thesis is to answer the questions of what product developers actually do, and how this can be taught at universities and colleges. The thesis is based on Schön's research on professionals' modes of work when solving unique problems; A designer, as other professionals at certain stages of their work, reflect by means of images and language. Schön uses Wittgenstein's ideas of language games and Polanyi's concept tacit knowiedge. The theas 1s based on two case studies, one case study describing and analyzmg a technical development project (Vmkelregelsvstemet) and one case study describing and analyzing an educational development project of planning a new engineering programme for Innovation and Design. Both case stuthes are analyzed and carried through using Schön's theories.
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| 7. |
- Brandt, Jerker
(författare)
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Tendon autografts for bridging nerve defects
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A new method, where a tendon segment – a tendon autograft – was used as graft material for peripheral nerve reconstruction, was developed. Defects, 10-15 mm long, in rat sciatic nerves were bridged by various modifications of tendons. A piece of an intact tendon and a tendon, that had been teased into a membrane and then rolled to form a loose “collagen roll”, supported axonal regeneration over a nerve defect. After modification by forming a tube of the teased tendon, axonal regeneration started after an initial delay period of 6.8 days, and axons then grew at a rate of 1.0 mm per day. Schwann cells migrated into the grafts from the proximal and distal nerve segments, proximally ahead of the regenerating axons. Macrophages were initially present at the periphery of the grafts but gradually increased in numbers inside the grafts. The tendon autograft was vascularized and the blood vessels entered the grafts from both the proximal and distal nerve segments. The tendon autograft supported recovery of muscle function measured as tetanic force of the gastrocnemius muscle, to the same extent as nerves reconstructed by a freeze-thawed muscle graft. Morphometrical analysis of the tibial nerve distal to the graft showed a correlation between the number of regenerating nerve fibers and recovery of muscle force. Initial experiments indicated that a teased and rolled tendon, which had been pretreated by attachment of nerve segments to allow migration of Schwann cells into the tendon, improved regeneration. To refine the tendon autograft and to enhance regeneration, cultured Schwann cells were added to grafts that were used to bridge a 10 mm long nerve defect. Addition of cultured Schwann cells resulted in a higher rate of axonal regeneration compared to untreated control rats. Analogous observations were made in the pretreated freeze-thawed muscle grafts. To address clinical demands of a faster procedure for production of Schwann cells, acutely dissociated Schwann cells from a previously injured nerve were added to tendon autografts bridging nerve defects. Addition of dissociated Schwann cells resulted in a longer axonal outgrowth seven days after nerve reconstruction compared to untreated control grafts. The use of tendon autografts with added acutely dissociated Schwann cells may be an alternative in bridging nerve defects in a clinical setting.
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| 8. |
- Dahlin, Lars, et al.
(författare)
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Basic science of peripheral nerve repair: Wallerian degeneration/growth cone
- 2004
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Ingår i: Operative Techniques in Orthopaedics. - : Elsevier BV. - 1048-6666. ; 14:2, s. 138-145
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Tidskriftsartikel (refereegranskat)abstract
- Trauma to a peripheral nerve trunk is a complex injury because it involves not only repair processes locally at the peripheral level, but it also engages repair and compensation mechanisms at central levels. The main actor is the fascinating and unique neuron with its supporting cells, which consist mainly of Schwann cells. In the neuron and in the Schwann cells, intracellular signaling mechanisms are initiated by the peripheral nerve injury and aim to turn the intracellular processes into a regenerative and proliferative state. The intracellular signaling mechanism is called signal transduction and works along the entire neuron, including the intracellular axonal transport system. A very delicate interaction occurs between the growth cones formed by the distal tip of the outgrowing axons and the environment into which the axons grow. A large number of changes occur in this environment due to the process of Wallerian degeneration caused by the injury. A thorough knowledge of the cellular and molecular repair mechanisms after peripheral nerve injury is the basis on which we can build new research with the aim to improve results after this devastating injury, because there are limitations in the pure surgical treatment of peripheral injury.
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| 9. |
- Dahlin, Lars, et al.
(författare)
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Schwann cells, acutely dissociated from a predegenerated nerve trunk, can be applied into a matrix used to bridge nerve defects in rats
- 2007
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Ingår i: Acta Neurochirurgica. Supplementum. - 0065-1419. ; 100, s. 57-60
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The gold standard to reconstruct a nerve defect is a conventional autologous nerve graft. There may be a lack of such grafts in severe nerve injuries. Alternatives to autologous nerve grafts are needed. METHODS: We have developed a technique where mainly Schwann cells are acutely dissociated from the ends of the severed nerve trunk after nerve injury. The technique does not require long-term cell culture procedures. The obtained cells, which can be dissociated within a few hours, are applied to a silicone tube or a tendon autograft used to bridge a nerve defect. FINDINGS: Dissociated cells from the ends of the severed nerve ends consist of more than 85% of Schwann cells. The remaining cells are ED1 stained macrophages. The cells survive transfer to a silicone tube or a tendon autograft which bridge the nerve defect. Axons do grow through such a graft filled with dissociated cells. CONCLUSION: Our novel model to obtain mainly Schwann cells by dissociation of the cells from the severed nerve ends after injury and add them to a matrix, thereby creating an artificial nerve graft, may be a new technique with potential clinical application in nerve reconstruction.
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| 10. |
- Nishiura, Y, et al.
(författare)
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Addition of cultured Schwann cells to tendon autografts and freeze-thawed muscle grafts improves peripheral nerve regeneration
- 2004
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Ingår i: Tissue Engineering. - 1076-3279. ; 10:1-2, s. 157-164
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Tidskriftsartikel (refereegranskat)abstract
- The effects of addition of Schwann cells on peripheral nerve regeneration through a novel graft material-the tendon autograft-and a conventional freeze-thawed muscle graft, were studied in the rat sciatic nerve. Adult Schwann cell cultures were established from predegenerated nerves. The Schwann cells were added to the autologous grafts by coculture (tendon autograft) or injection (freeze-thawed muscle graft). Both graft types supported adherence of the added Schwann cells. Addition of cultured Schwann cells to the two different graft models improved regeneration by increasing the rate of axonal outgrowth as compared with similar grafts without added cells.
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| 11. |
- Rutgersson, Carolin, 1983, et al.
(författare)
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Long-term application of Swedish sewage sludge on farmland does not cause clear changes in the soil bacterial resistome
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 137
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Tidskriftsartikel (refereegranskat)abstract
- The widespread practice of applying sewage sludge to arable land makes use of nutrients indispensable for crops and reduces the need for inorganic fertilizer, however this application also provides a potential route for human exposure to chemical contaminants and microbial pathogens in the sludge. A recent concern is that such practice could promote environmental selection and dissemination of antibiotic resistant bacteria or resistance genes. Understanding the risks of sludge amendment in relation to antibiotic resistance development is important for sustainable agriculture, waste treatment and infectious disease management. To assess such risks, we took advantage of an agricultural field trial in southern Sweden, where land used for growing different crops has been amended with sludge every four years since 1981. We sampled raw, semi-digested and digested and stored sludge together with soils from the experimental plots before and two weeks after the most recent amendment in 2017. Levels of selected antimicrobials and bioavailable metals were determined and microbial effects were evaluated using both culture-independent metagenome sequencing and conventional culturing. Antimicrobials or bioavailable metals (Cu and Zn) did not accumulate to levels of concern for environmental selection of antibiotic resistance, and no coherent signs, neither on short or long time scales, of enrichment of antibiotic-resistant bacteria or resistance genes were found in soils amended with digested and stored sewage sludge in doses up to 12 metric tons per hectare. Likewise, only very few and slight differences in microbial community composition were observed after sludge amendment. Taken together, the current study does not indicate risks of sludge amendment related to antibiotic resistance development under the given conditions. Extrapolations should however be done with care as sludge quality and application practices vary between regions. Hence, the antibiotic concentrations and resistance load of the sludge are likely to be higher in regions with larger antibiotic consumption and resistance burden than Sweden.
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| 12. |
- Saqlain, Murshid, et al.
(författare)
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Stochastic differential equations modelling of levodopa concentration in patients with Parkinson's disease
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this study is to investigate a pharmacokinetic model of levodopa concentration in patients with Parkinson's disease by introducing stochasticity so that inter-individual variability may be separated into measurement and system noise. It also aims to investigate whether the stochastic differential equations (SDE) model provide better fits than its ordinary differential equations (ODE) counterpart, by using a real data set. Westin et al. developed a pharmacokinetic-pharmacodynamic model for duodenal levodopa infusion described by four ODEs, the first three of which define the pharmacokinetic model. In this study, system noise variables are added to the aforementioned first three equations through a standard Wiener process, also known as Brownian motion. The R package PSM for mixed-effects models is used on data from previous studies for modelling levodopa concentration and parameter estimation. First, the diffusion scale parameter, σ, and bioavailability are estimated with the SDE model. Second, σ is fixed to integer values between 1 and 5, and bioavailability is estimated. Cross-validation is performed to determine whether the SDE based model explains the observed data better or not by comparingthe average root mean squared errors (RMSE) of predicted levodopa concentration. Both ODE and SDE models estimated bioavailability to be about 88%. The SDE model converged at different values of σ that were signicantly different from zero while estimating bioavailability to be about 88%. The average RMSE for the ODE model wasfound to be 0.2980, and the lowest average RMSE for the SDE model was 0.2748 when σ was xed to 4. Both models estimated similar values for bioavailability, and the non-zero σ estimate implies that the inter-individual variability may be separated. However, the improvement in the predictive performance of the SDE model turned out to be rather small, compared to the ODE model.
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| 13. |
- Svensson, Johan, et al.
(författare)
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Environmental concentrations of an androgenic progestin disrupts the seasonal breeding cycle in male three-spined stickleback (Gasterosteus aculeatus)
- 2014
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Ingår i: Aquatic Toxicology. - : Elsevier BV. - 0166-445X .- 1879-1514. ; 147, s. 84-91
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic steroid hormones from contraceptive pharmaceuticals have become global aquatic contaminants. Progestins, the synthetic analogs to progesterone, are receiving increasing attention as contaminants and have been shown to impair reproduction in fish and amphibians at low ng L-1 concentrations. Certain progestins, such as levonorgestrel have androgenic properties and seem to be several orders of magnitude more potent in terms of reproductive impairment in fish than non-androgenic progestins and progestagens. We recently reported that levonorgestrel has strong androgenic effects in female three-spined sticklebacks (Gasterosteus aculeatus), including induction of the normally male-specific glue protein spiggin and suppression of vitellogenesis. In light of this we investigated if exposure to levonorgestrel could disrupt the highly androgen-dependent seasonal reproductive cycle in male sticklebacks. Male sticklebacks that were in the final stage of a breeding period were exposed to various concentrations of levonorgestrel for six weeks in winter conditions in terms of light and temperature, after which reproductive status was evaluated from gross morphology, histology and key gene transcript levels. During the experimental period the controls had transitioned from full breeding condition into the non-breeding state, including regression of secondary sex characteristics, cessation of spiggin production in the kidney, and resumption of spermatogenesis in the testes. This is ascribed to the natural drop in plasma androgen levels after breeding. However, in the groups concurrently exposed to levonorgestrel, transition to the non-breeding condition was dose-dependently inhibited. Our results show that levonorgestrel can disrupt the seasonal breeding cycle in male sticklebacks. The fitness costs of such an effect could be detrimental to natural stickleback populations. Some effects occurred at a levonorgestrel concentration of 6.5 ng L-1, well within the range of levonorgestrel levels in surface waters and may therefore occur in progestin-contaminated waters. Furthermore, the effects by levonorgestrel in the present study were likely mediated mainly by its androgenic activity, and the low concentration at which they occurred makes levonorgestrel one of the most potent androgenic contaminants known.
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| 14. |
- Svensson, Johan, et al.
(författare)
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The Synthetic Progestin Levonorgestrel Is a Potent Androgen in the Three-Spined Stickleback (Gasterosteus aculeatus)
- 2013
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 47:4, s. 2043-2051
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Tidskriftsartikel (refereegranskat)abstract
- The use of progestins has resulted in contamination of aquatic environments and some progestins have in experimental studies been shown to impair reproduction in fish and amphibians at low ng L-1 concentrations. The mechanisms underlying their reproductive toxicity are largely unknown. Some progestins, such as levonorgestrel (LNG), exert androgenic effects in mammals by activating the androgen receptor (AR). Male three-spined stickleback (Gasterosteus aculeatus) kidneys produce spiggin, a gluelike glycoprotein used in nest building, and its production is directly governed by androgens. Spiggin is normally absent in females but its production in female kidneys can be induced by AR agonists. Spiggin serves as the best known biomarker for androgens in fish. We exposed adult female sticklebacks to LNG at 5.5, 40, and 358 ng L-1 for 21 days. Androgenic effects were found at LNG concentrations >= 40 ng L-1 including induction of spiggin transcription, kidney hypertrophy, and suppressed liver vitellogenin transcription. These are the first in vivo quantitative data showing that LNG is a potent androgen in fish supporting the contention that androgenic effects of certain progestins contribute to their reproductive toxicity.
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