| 1. |
- Anckarsäter, Henrik, et al.
(författare)
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Reduced frontotemporal perfusion in psychopathic personality
- 2002
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Ingår i: Psychiatry Research. - 1872-7123. ; 114:2, s. 81-94
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Tidskriftsartikel (refereegranskat)abstract
- Several brain-imaging studies have found associations between aberrant functioning in the frontal and temporal lobes and violent offending. We have previously reported decreased frontotemporal perfusion unrelated to psychosis, substance abuse, or current medication in 21 violent offenders. In the present study, we compared the regional cerebral blood flow (rCBF) in a new group of 32 violent offenders to scores on the Psychopathy Checklist-Revised (PCL-R), which rates two aspects of psychopathy: disturbed interpersonal attitudes (Factor 1) and impulsive antisocial behavior (Factor 2). A recently proposed model has split Factor 1 into a new Factor 1 (deceitful interpersonal style), a new Factor 2 (affective unresponsiveness), and a Factor 3, which approximately corresponds to the old Factor 2. The rCBF was assessed by single-photon emission computed tomography (SPECT) with technetium-99m-d,l-hexamethylpropyleneamine oxime (HMPAO) in regions of interest (ROIs) placed in accordance with fusioned magnetic resonance images (MRI) and SPECT scans. Significant negative correlations were found between interpersonal features of psychopathy (the old and especially the new Factor 1) and the frontal and temporal perfusion. The two most clearly associated ROIs were the head of the caudate nuclei and the hippocampi. These findings in a group of violent offenders living under the same conditions, which reduced the number of state-related confounders, add to the evidence indicating that aberrant frontotemporal activity may be a factor in violent behavior.
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| 2. |
- Baranowska, Izabella, et al.
(författare)
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Sensory ataxic neuropathy in golden retriever dogs is caused by a deletion in the mitochondrial tRNATyr gene
- 2009
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 5:5, s. e1000499-
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Tidskriftsartikel (refereegranskat)abstract
- Sensory ataxic neuropathy (SAN) is a recently identified neurological disorder in golden retrievers. Pedigree analysis revealed that all affected dogs belong to one maternal lineage, and a statistical analysis showed that the disorder has a mitochondrial origin. A one base pair deletion in the mitochondrial tRNA(Tyr) gene was identified at position 5304 in affected dogs after re-sequencing the complete mitochondrial genome of seven individuals. The deletion was not found among dogs representing 18 different breeds or in six wolves, ruling out this as a common polymorphism. The mutation could be traced back to a common ancestor of all affected dogs that lived in the 1970s. We used a quantitative oligonucleotide ligation assay to establish the degree of heteroplasmy in blood and tissue samples from affected dogs and controls. Affected dogs and their first to fourth degree relatives had 0-11% wild-type (wt) sequence, while more distant relatives ranged between 5% and 60% wt sequence and all unrelated golden retrievers had 100% wt sequence. Northern blot analysis showed that tRNA(Tyr) had a 10-fold lower steady-state level in affected dogs compared with controls. Four out of five affected dogs showed decreases in mitochondrial ATP production rates and respiratory chain enzyme activities together with morphological alterations in muscle tissue, resembling the changes reported in human mitochondrial pathology. Altogether, these results provide conclusive evidence that the deletion in the mitochondrial tRNA(Tyr) gene is the causative mutation for SAN.
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| 3. |
- Fredin, Maria Fritsch, 1970, et al.
(författare)
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Predicting and monitoring colitis development in mice by micro-computed tomography
- 2008
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 14:4, s. 491-499
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Computed tomography (CT) has been developed as a tool for monitoring human inflammatory bowel disease (IBD). The aim of this study was to evaluate colon wall thickness as a noninvasive marker in the dextran sodium sulfate (DSS) mouse model of colitis using micro-CT. METHODS: Mice were examined by micro-CT 1, 2, or 4 times between day 0 (d0) and d26 after induction of colitis to document the kinetics of changes in colon wall thickness and its relation to colitis development. RESULTS: DSS-treated mice displayed a significantly thicker colon wall at all timepoints (days 5, 8, 12, 19, and 26) investigated compared to healthy controls. Colon wall thickness showed a good correlation to the macroscopic grading of colitis (r = 0.81). The increase in colon wall thickness occurred mainly during the acute phase of colitis (between days 5 and 12) and did not progress much further in the chronic phase of colitis (d26). Colon wall thickness at d26 was thereby predicted by measurements at d12. All mice did not respond equally to DSS and this difference was manifest during the first 2 weeks of colitis, providing an important tool in stratifying responders from nonresponders. CONCLUSIONS: While the potential impact of handling and anesthesia should be considered on repeated micro-CT, irradiation exposure during repeated micro-CT did not affect the development of colitis. Thus, the results suggest that micro-CT can be used for monitoring and prediction of the inflammatory response in mouse colitis in future therapeutic studies.
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| 4. |
- Hultin, Leif, 1962
(författare)
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On Neuromagnetic Assessment of the Contingent Negative Variation
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The contingent negative variation, CNV, is a cognitive process related to anticipation and motor preparation. In the present work the CNV was studied by the use of magnetoencephalography, MEG. MEG can achieve high spatial and temporal information about neuroelectrical activity and is thus a promising tool for gaining a better understanding of the complex neurological processes related to the CNV. The neuromagnetic recording of the CNV is, however, a nontrivial task that requires extensive signal processing and carefully designed experimental protocols. There are further reasons to assume that the neuromagnetic fields related to CNV are generated by a different electrophysiological phenomenon from that of neuromagnetic fields of shorter duration. The contingent magnetic variation, CMV, in a warned choice reaction time task was studied in healthy subjects. Based on the spatial and temporal properties of the recorded neuromagnetic signals, four slow components could be separated from the CMV. Three early slow components peaked in the interval 300 - 700 ms after the warning stimulus. The late component started 500 - 700 ms before the imperative stimulus and ended abruptly at the delivery of the imperative stimuli. Large interindividual differences were seen in the early components of the CMV, and general conclusions in terms of source localizations could not be drawn from the data obtained. The results suggest, however, that the dominant sources of the late component are symmetrically located in the left and right premotor areas. It is proposed that the glial buffering current, GBC, is a potential source of sustained neuromagnetic fields, and that it results in an equivalent current dipole directed perpendicular from the surface of the cortex, the same as could be expected due to post-synaptic currents, PSCs. Some of the main features of neuromagnetic fields generated by GBC, compared to fields of PSC origin, are: temporal and spatial integration, phase reversal at the termination of neural activity, and finally that magnetic fields are evoked also by pre-synaptic activity, inhibitory activity and activity in nonpyramidal neurons. Algorithms are developed for calculations of iso-field maps using a three-dimensional, rule-assisted interpolation algorithm on an ellipsoidal surface. Benefits of the algorithm developed, compared to previously used algorithms, include true three-dimensional interpolation, accurate handling of iso-map boundaries, and fast updating of iso-field maps at time or view-angle changes. This thesis further describes the paradigm, the recording procedures, and the artifact rejection algorithms developed to avoid electric and magnetic artifacts and to minimize the influence of the variance in the alertness of the subject on the result. The reaction time is one important parameter in the determination of the alertness. Algorithms are developed for automatic EMG onset detection using rectified median filtered EMG signals.
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| 5. |
- Janssen, Pieter, et al.
(författare)
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A Novel Method for Study of Gastric Mechanical Functions in Conscious Mice
- 2009
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Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 54:2, s. 222-231
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Tidskriftsartikel (refereegranskat)abstract
- A novel method has been developed for simultaneous study of gastric emptying, antral motility, and gastric muscle tone in conscious mice. Intragastric pressure was measured during infusion of an X-ray-opaque, viscous meal through a chronically implanted gastric fistula (0.25 ml/min). Compared with vehicle treatment, molsi-domine (nitric oxide donor) and atropine (muscarinic receptor antagonist) treatment significantly reduced the area under the intragastric pressure curve (AUC) by 37 +/- 4% and 35 +/- 3%, respectively, (mean +/- S.E.M.) whereas N-G-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase inhibitor) significantly increased the AUC by 20 +/- 3%. Atropine also significantly reduced the frequency and amplitude of stomach contraction-induced intragastric pressure waves while molsidomine only reduced the frequency. Gastric emptying, as assessed by X-ray imaging, was significantly delayed after L-NAME and atropine treatment. This methodology is the first to enable simultaneous assessment of gastric emptying, antral motility, and gastric tone in conscious mice and confirmed the important role of nitrergic and cholinergic innervation.
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| 6. |
- Janssen, Pieter, et al.
(författare)
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A novel method to assess gastric accommodation and peristaltic motility in conscious rats
- 2008
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 43:1, s. 34-43
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To simultaneously study gastric accommodation and peristaltic motility in the whole stomach of conscious rats by measuring intragastric pressure (IGP) during test-meal infusion. Material and methods. After an overnight fast, a test-meal infusion system and a catheter to measure IGP were connected to a chronically implanted gastric fistula. IGP was measured during infusion of an X-ray-opaque, non-nutritious viscous test meal (0.25-2 ml min(-1)); gastric motility and emptying were assessed by X-ray fluoroscopy. Peristaltic motility-induced IGP waves were quantified as a motility index (wave amplitude divided by wavelength). Experiments were performed in Sprague-Dawley (SD) rats and in the high-anxiety Wistar Kyoto (WKY) rats. Moreover, the effects of 30 mg kg(-1) N-G-nitro-L-arginine methyl ester (L-NAME), 1 mg kg(-1) atropine or 20 mg kg(-1) molsidomine were tested in SD rats. Results. Compared with SD rats, IGP increased significantly faster during stomach distension in WKY rats, indicating impaired accommodation in the latter strain. Motility indices did not differ between the two strains. L-NAME significantly increased IGP during stomach distension, indicating decreased gastric accommodation. However, no change in motility indices was observed with L-NAME. Treatment with atropine significantly increased IGP and decreased motility indices, indicating decreased gastric accommodation and motility. Molsidomine significantly decreased IGP during stomach distension but did not affect motility. The results correspond to X-ray observations, and confirm literature data. Conclusions. We conclude that IGP measurement during test-meal infusion represents an efficient and novel method to compare gastric accommodation and peristaltic motility in the whole stomach of conscious rats.
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| 7. |
- Janssen, Pieter, et al.
(författare)
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Effect of Muscarinic and Nicotinic Receptor Antagonism on Rat Gastric Motor Activity
- 2010
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Ingår i: Pharmacology. - : S. Karger AG. - 0031-7012 .- 1423-0313. ; 85:5, s. 272-279
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Our aim was to investigate whether muscarinic and nicotinic receptors mediate nitric oxide release during motor events in the rat stomach. Methods: Isolated rat stomach volume changes were monitored in an organ bath setup with an intragastric balloon coupled to a barostat and studied in basal conditions and during electrical vagal stimulation (EVS). In conscious rats, the intragastric pressure (IGP) was measured during test meal infusion. Results: In the presence of N-G-nitro-L -arginine methyl ester (L-NAME; 0.1 mmol/l), EVS induced significant gastric contractions (mean +/- SEM = 0.27 +/- 0.04 ml; n = 6) that could be blocked by atropine (3 mu mol/l) and hexamethonium (0.1 mmol/l). In the presence of atropine and/or hexamethonium, EVS-induced relaxations could not be blocked by L-NAME, while exogenous nitric oxide could still relax the stomach. In conscious rats, atropine (1 mg kg(-1)) initially decreased IGP, while during further distension it increased IGP. In the presence of L -NAME (30 mg kg(-1)) atropine consistently decreased IGP.
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| 8. |
- Nawaz, Muhammad, et al.
(författare)
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Lipid Nanoparticles Deliver the Therapeutic VEGFA mRNA In Vitro and In Vivo and Transform Extracellular Vesicles for Their Functional Extensions
- 2023
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Ingår i: Advanced Science. - : John Wiley & Sons. - 2198-3844. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Lipid nanoparticles (LNPs) are currently used to transport functional mRNAs, such as COVID-19 mRNA vaccines. The delivery of angiogenic molecules, such as therapeutic VEGF-A mRNA, to ischemic tissues for producing new blood vessels is an emerging strategy for the treatment of cardiovascular diseases. Here, the authors deliver VEGF-A mRNA via LNPs and study stoichiometric quantification of their uptake kinetics and how the transport of exogenous LNP-mRNAs between cells is functionally extended by cells’ own vehicles called extracellular vesicles (EVs). The results show that cellular uptake of LNPs and their mRNA molecules occurs quickly, and that the translation of exogenously delivered mRNA begins immediately. Following the VEGF-A mRNA delivery to cells via LNPs, a fraction of internalized VEGF-A mRNA is secreted via EVs. The overexpressed VEGF-A mRNA is detected in EVs secreted from three different cell types. Additionally, RNA-Seq analysis reveals that as cells’ response to LNP-VEGF-A mRNA treatment, several overexpressed proangiogenic transcripts are packaged into EVs. EVs are further deployed to deliver VEGF-A mRNA in vitro and in vivo. Upon equal amount of VEGF-A mRNA delivery via three EV types or LNPs in vitro, EVs from cardiac progenitor cells are the most efficient in promoting angiogenesis per amount of VEGF-A protein produced. Intravenous administration of luciferase mRNA shows that EVs could distribute translatable mRNA to different organs with the highest amounts of luciferase detected in the liver. Direct injections of VEGF-A mRNA (via EVs or LNPs) into mice heart result in locally produced VEGF-A protein without spillover to liver and circulation. In addition, EVs from cardiac progenitor cells cause minimal production of inflammatory cytokines in cardiac tissue compared with all other treatment types. Collectively, the data demonstrate that LNPs transform EVs as functional extensions to distribute therapeutic mRNA between cells, where EVs deliver this mRNA differently than LNPs.
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| 9. |
- Tejedor, Sandra, et al.
(författare)
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The Combination of Vascular Endothelial Growth Factor A (VEGF-A) and Fibroblast Growth Factor 1 (FGF1) Modified mRNA Improves Wound Healing in Diabetic Mice : An Ex Vivo and In Vivo Investigation
- 2024
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1). Methods: An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination. Results: The combination of VEGF-A and FGF1 demonstrated increased vascular sprouting in the ex vivo mouse aortic ring model, and topical administration of a combination of VEGF-A and FGF1 mRNAs formulated in lipid nanoparticles (LNPs) in mouse skin wounds promoted faster wound closure and increased neovascularization seven days post-surgical wound creation. RNA-sequencing analysis of skin samples at day three post-wound creation revealed a strong transcriptional response of the wound healing process, with the combined treatment showing significant enrichment of genes linked to skin growth. Conclusion: f-LNPs encapsulating VEGF-A and FGF1 mRNAs present a promising approach to improving the scarring process in DFU.
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