| 41. |
- Klassen, Henry, et al.
(författare)
-
Progenitor cells from the porcine neural retina express photoreceptor markers after transplantation to the subretinal space of allorecipients
- 2007
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 25:5, s. 1222-1230
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Tidskriftsartikel (refereegranskat)abstract
- Work in rodents has shown that cultured retinal progenitor cells (RPCs) integrate into the degenerating retina, thus suggesting a potential strategy for treatment of similar degenerative conditions in humans. To demonstrate the relevance of the rodent work to large animals, we derived progenitor cells from the neural retina of the domestic pig and transplanted them to the laser-injured retina of allorecipients. Prior to grafting, immunocytochemical analysis showed that cultured porcine RPCs widely expressed neural cell adhesion molecule, as well as markers consistent with immature neural cells, including nestin, Sox2, and vimentin. Subpopulations expressed the neurodevelopmental markers CD-15, doublecortin, beta-III tubulin, and glial fibrillary acidic protein. Retina-specific markers expressed included the bipolar marker protein kinase C alpha and the photoreceptor-associated markers recoverin and rhodopsin. In addition, reverse transcription-polymerase chain reaction showed expression of the transcription factors Dach1, Hes1, Lhx2, Pax6, Six3, and Six6. Progenitor cells prelabeled with vital dyes survived as allografts in the subretinal space for up to 5 weeks (11 of 12 recipients) without exogenous immune suppression. Grafted cells expressed transducin, recoverin, and rhodopsin in the pig subretinal space, suggestive of differentiation into photoreceptors or, in a few cases, migrated into the neural retina and extended processes, the latter typically showing radial orientation. These results demonstrate that many of the findings seen with rodent RPCs can be duplicated in a large mammal. The pig offers a number of advantages over mice and rats, particularly in terms of functional testing and evaluation of the potential for clinical translation to human subjects.
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| 42. |
- Kragelund, C., et al.
(författare)
-
Scandinavian fellowship for oral pathology and oral medicine : guidelines for oral pathology and oral medicine in the dental curriculum
- 2012
-
Ingår i: European journal of dental education. - Hoboken : Wiley-Blackwell. - 1396-5883 .- 1600-0579. ; 16:4, s. 246-253
-
Tidskriftsartikel (refereegranskat)abstract
- In Scandinavia, as in many European countries, most patients consult their general dentist once a year or more. This gives the dentist a unique opportunity and an obligation to make an early diagnosis of oral diseases, which is beneficial for both the patient and the society. Thus, the dentist must have knowledge of clinical symptoms, local and systemic signs and clinical differential diagnoses to make an accurate diagnosis. The dentist must be competent in selecting appropriate diagnostic tests, for example, tissue biopsy and microbiological samples, and conducting them correctly, as well as in interpreting test results and taking appropriate action accordingly. Furthermore, the dentist must be aware of diseases demanding multidisciplinary cooperation and be able to recognise his/her professional limitation, and to refer to other specialists when required. The dental curriculum changes over time as new approaches, treatments and diagnostic possibilities develop. Likewise, the role of the dentist in the community changes and may vary in different countries. As members of the Scandinavian Fellowship for Oral Pathology and Oral Medicine and subject representatives of oral pathology and oral medicine, we feel obliged to contribute to the discussion of how the guidelines of the dental curriculum support the highest possible standards of dental education. This article is meant to delineate a reasonable standard of oral pathology and oral medicine in the European dental curriculum and to guide subject representatives in curriculum development and planning. We have created an advisory topic list in oral pathology and oral medicine.
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| 43. |
- Kragelund, C, et al.
(författare)
-
Scandinavian fellowship for oral pathology and oral medicine : statement on oral pathology and oral medicine in the European dental curriculum
- 2010
-
Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 39:10, s. 800-801
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: For many years, dentists have migrated between the Scandinavian countries without an intentionally harmonized dental education. The free movement of the workforce in the European Union has clarified that a certain degree of standardization or harmonization of the European higher education acts, including the dental education, is required. As a result of the Bologna process, the Association for Dental Education in Europe and the thematic network DentEd have generated guidelines in the document 'Profile and Competences for the European Dentist' (PCD). This document is meant to act as the leading source in revisions of dental curricula throughout Europe converging towards a European Dental Curriculum. In order to render the best conditions for future curriculum revisions providing the best quality dentist we feel obliged to analyse and comment the outlines of oral pathology and oral medicine in the PCD.METHODS: The representatives agreed upon definitions of oral pathology and oral medicine, and competences in oral pathology and oral medicine that a contemporary European dentist should master. The competences directly related to oral pathology and oral medicine were identified, within the PCD.RESULTS: The subject representatives suggested eighteen additions and two rewordings of the PCD, which all were substantiated by thorough argumentation.PERSPECTIVES: Hopefully, this contribution will find support in future revisions of the PCD in order to secure the best quality dental education.
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| 44. |
- Krause, Diana N., et al.
(författare)
-
Hormonal influences in migraine — interactions of oestrogen, oxytocin and CGRP
- 2021
-
Ingår i: Nature Reviews Neurology. - : Springer Science and Business Media LLC. - 1759-4758 .- 1759-4766. ; 17:10, s. 621-633
-
Forskningsöversikt (refereegranskat)abstract
- Migraine is ranked as the second highest cause of disability worldwide and the first among women aged 15–49 years. Overall, the incidence of migraine is threefold higher among women than men, though the frequency and severity of attacks varies during puberty, the menstrual cycle, pregnancy, the postpartum period and menopause. Reproductive hormones are clearly a key influence in the susceptibility of women to migraine. A fall in plasma oestrogen levels can trigger attacks of migraine without aura, whereas higher oestrogen levels seem to be protective. The basis of these effects is unknown. In this Review, we discuss what is known about sex hormones and their receptors in migraine-related areas in the CNS and the peripheral trigeminovascular pathway. We consider the actions of oestrogen via its multiple receptor subtypes and the involvement of oxytocin, which has been shown to prevent migraine attacks. We also discuss possible interactions of these hormones with the calcitonin gene-related peptide (CGRP) system in light of the success of anti-CGRP treatments. We propose a simple model to explain the hormone withdrawal trigger in menstrual migraine, which could provide a foundation for improved management and therapy for hormone-related migraine in women.
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| 45. |
- Kyhn, Maria Voss, et al.
(författare)
-
Acute retinal ischemia caused by controlled low ocular perfusion pressure in a porcine model. Electrophysiological and histological characterisation
- 2009
-
Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835. ; 88:6, s. 1100-1106
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to establish, and characterize a porcine model of acute, controlled retinal ischemia. The controlled retinal ischemia was produced by clamping the ocular perfusion pressure (OPP) in the left eye to 5 mm Hg for 2 h. The OPP was defined as mean arterial blood pressure (MAP) minus the intraocular pressure (IOP). It was clamped to 0-30 mm Hg by continuous monitoring of MAP and adjustment of the IOP, which was controlled by cannulation of the anterior chamber. Inner retinal function was assessed by induced multifocal electroretinography (mfERG) with comparisons of the amplitudes obtained in the experimental, left eye, and the control, right eye. Quantitative histology was performed to measure the survival of ganglion cells, amacrine cells and horizontal cells 2-6 weeks after the ischemic insult. An OPP of 5 mm Hg for 2 h induced significant reductions in the amplitudes of iN1 to 20% (CI: 13-30%), and iPr2 to 14% (95% CI: 8-22%) of their baseline values. No signs of recovery were found within the 6-week observation period. Quantitative histology revealed a highly significant reduction in the number of ganglion cells, amacrine cells and horizontal cells after the ischemic insult. This model seems to be suitable for investigations of therapeutic initiatives in diseases involving acute retinal ischemia. (C) 2009 Elsevier Ltd. All rights reserved.
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| 46. |
- Kyhn, Maria Voss, et al.
(författare)
-
Delayed administration of glial cell line-derived neurotrophic factor (GDNF) protects retinal ganglion cells in a pig model of acute retinal ischemia
- 2009
-
Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835 .- 1096-0007. ; 89:6, s. 1012-1020
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigates whether intravitreal administration of glial cell line-derived neurotrophic factor (GDNF) enhances survival of NeuN positive retinal cells in a porcine model of retinal ischemia. 16 pigs were subjected to an ischemic insult where intraocular pressure was maintained at 5 mmHg below mean arterial blood pressure for 2 h. The mean IOP during the ischemic insult was 79.5 mmHg (s.e.m. 2.1 mmHg, n = 15). Three days after the insult the pigs received an intravitreal injection of GDNF microspheres or blank microspheres. The pigs were evaluated by way of multifocal electroretinography (mfERG), quantification of NeuN positive cells and evaluation of the degree of retinal perivasculitis and inflammation 6 weeks after the insult. In the post-injection eyes (days 14, 28 and 42), the ratios of the iN1 and the iP2 amplitudes were 0.10 (95% CI: 0.05-0.15) and 0.09 (95% CI: 0.04-0.16) in eyes treated with blank microspheres, and 0.24 (95% CI: 0.18-0.32) and 0.23 (95% CI: 0.15-0.33) in eyes treated with GDNF microspheres. These differences were statistically significant (P < 0.05). The number of NeuN positive cells in the area of the visual streak area was significantly higher in eyes injected with GDNF microspheres compared to eyes injected with blank microspheres. In eyes injected with GDNF microspheres the ganglion cell count was 9.5/field (s.e.m.: 2.1, n = 8), in eyes injected with blank microspheres it was 3.5/field (s.e.m.: 1.2, n = 7). This difference was statistically significant (P < 0.05). There was also a significant difference (P < 0.01) in the degree of perivasculiitis between GDNF treated eyes (median perivasculitis score 1.5) and blank treated eyes (median perivasculitis score 3.0). In conclusion, injection of GDNF microspheres 3 days after an ischemic insult results in functional and morphological rescue of NeuN positive cells in a porcine model of acute ocular ischemia. (C) 2009 Elsevier Ltd. All rights reserved.
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| 47. |
- Lavik, EB, et al.
(författare)
-
Fabrication of degradable polymer scaffolds to direct the integration and differentiation of retinal progenitors
- 2005
-
Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 26:16, s. 3187-3196
-
Tidskriftsartikel (refereegranskat)abstract
- Retinal progenitor cells (RPCs) are self-renewing cells capable of differentiating into the different retinal cell types including photoreceptors, and they have shown promise as a source of replacement cells in experimental models of retinal degeneration. We hypothesized that a biodegradable polymer scaffold could deliver these cells to the subretinal space in a more organized manner than bolus injections, while also providing the graft with laminar organization and structural guidance channels. We fabricated highly porous scaffolds from blends of poly(L-lactic acid) and poly(lactic-co-glycolic acid) using a variety of techniques to produce pores oriented normal to the plane of the scaffold. RPCs were seeded on the polymer scaffolds and cultured for 14 days. Seeded scaffolds were then either fixed for characterization or used in an explant or in vivo rat model. The, scaffolds were fully covered by RPCs in 3 days. Attachment of RPCs to the polymer scaffold was associated with down-regulation of immature markers and up-regulation of markers of differentiation. This suggests that the scaffold may promote differentiation of RPCs. The seeded cells elaborated cellular processes and aligned in the scaffold in conjunction with degenerating retinal explants. The cells also exhibited morphologies consistent with photoreceptors including a high degree of polarization of the cells. This data suggests that the scaffold may be a means to assist in the promotion of photoreceptor phenotypes. Implantation of the seeded scaffold into the rat eye is associated with increased RPC survival. Taken together, these data suggest that these polymer scaffolds provide a useful means for delivering RPCs to the subretinal space and may assist in the formation of retinal cell phenotypes, although it is clear that more cues are needed to direct the differentiation of RPCs into functional photoreceptors.
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| 48. |
- Le, Thi Lisa, et al.
(författare)
-
CGRP in rat mesenteric artery and vein - receptor expression, CGRP presence and potential roles
- 2020
-
Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999. ; 875
-
Tidskriftsartikel (refereegranskat)abstract
- CGRP is a potent dilator of arteries and despite rich perivascular CGRP immunoreactivity in both arteries and veins the role of CGRP in veins remains unknown. The aim of the current study was to compare perivascular CGRP immunoreactivity and expression of CGRP receptor mRNA and CGRP receptor immunoreactivity in rat mesenteric arteries and veins. Furthermore, potential vasomotor effects of CGRP were explored in veins. Immunohistochemical studies reproduced rich perivascular CGRP innervation in arteries and in veins. Further, the presence of mRNA encoding the CGRP receptor subunits, CLR and RAMP1, were demonstrated in both arteries and veins using qPCR. Before comparing the vasoactive effects of CGRP in arteries and veins, we aimed to identify an experimental setting where vasomotor responses could be detected. Therefore, a length-tension study was performed in artery and vein segments. Whereas the arteries showed the characteristic monophasic curve with an IC/IC100 value of 0.9, surprisingly the veins showed a biphasic response with two corresponding IC/IC100 values of 0.7 and 0.9, respectively. There was no significant difference between fresh and cultured vasculature segments. To investigate whether a potential tension-dependent CGRP-induced dilation of veins caused the decline between the two IC/IC100 peaks, a second study was performed, with the CGRP receptor antagonist, BIBN4096BS (olcegepant) and the sensory nerve secretagogue, capsaicin. No significant vascular role of endogenous perivascular CGRP in mesenteric veins could be concluded, and a potential role of the rich perivascular CGRP and CGRP receptor abundancy in veins remains unknown.
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| 49. |
- Lukács, Melinda, et al.
(författare)
-
Dural administration of inflammatory soup or Complete Freund's Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion.
- 2015
-
Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Migraine is a painful disorder with a huge impact on individual and public health. We hypothesize that migraine pain originates from a central mechanism that results secondarily in hypersensitivity in peripheral afferents associated with the cerebral and cranial blood vessels. It has previously been shown that application of inflammatory or algesic substances onto the dura mater or chemical stimulation of the dural receptive fields causes hypersensitivity to mechanical and thermal stimulation together with direct activation of the TG. We asked whether local inflammation of dura mater induces inflammatory activation in the trigeminal ganglion.
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| 50. |
- Maddahi, Aida, et al.
(författare)
-
Progesterone distribution in the trigeminal system and its role to modulate sensory neurotransmission : influence of sex
- 2023
-
Ingår i: Journal of Headache and Pain. - 1129-2369. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Women are disproportionately affected by migraine, representing up to 75% of all migraine cases. This discrepancy has been proposed to be influenced by differences in hormone levels between the sexes. One such hormone is progesterone. Calcitonin gene-related peptide (CGRP) system is an important factor in migraine pathophysiology and could be influenced by circulating hormones. The purpose of this study was to investigate the distribution of progesterone and its receptor (PR) in the trigeminovascular system, and to examine the role of progesterone to modulate sensory neurotransmission. Methods: Trigeminal ganglion (TG), hypothalamus, dura mater, and the basilar artery from male and female rats were carefully dissected. Expression of progesterone and PR proteins, and mRNA levels from TG and hypothalamus were analyzed by immunohistochemistry and real-time quantitative PCR. CGRP release from TG and dura mater were measured using an enzyme-linked immunosorbent assay. In addition, the vasomotor effect of progesterone on male and female basilar artery segments was investigated with myography. Results: Progesterone and progesterone receptor -A (PR-A) immunoreactivity were found in TG. Progesterone was located predominantly in cell membranes and in Aδ-fibers, and PR-A was found in neuronal cytoplasm and nucleus, and in satellite glial cells. The number of positive progesterone immunoreactive cells in the TG was higher in female compared to male rats. The PR mRNA was expressed in both hypothalamus and TG; however, the PR expression level was significantly higher in the hypothalamus. Progesterone did not induce a significant change neither in basal level nor upon stimulated release of CGRP from dura mater or TG in male or female rats when compared to the vehicle control. However, pre-treated with 10 µM progesterone weakly enhanced capsaicin induced CGRP release observed in the dura mater of male rats. Similarly, in male basilar arteries, progesterone significantly amplified the dilation in response to capsaicin. Conclusions: In conclusion, these results highlight the potential for progesterone to modulate sensory neurotransmission and vascular responses in a complex manner, with effects varying by sex, tissue type, and the nature of the stimulus. Further investigations are needed to elucidate the underlying mechanisms and physiological implications of these findings.
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