| 5871. |
- Jenei, Veronica, et al.
(författare)
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Increased cell-cell adhesion, a novel effect of R-(-)-deprenyl
- 2005
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Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 112:11, s. 1433-1445
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Tidskriftsartikel (refereegranskat)abstract
- The neuroprotective effect of the antiparkinsonian monoamine oxidase (MAO)-B inhibitor, R-(-)-deprenyl has been under investigation for years. Cytoskeleton, a main component of cell adhesion, is involved in the development of R-(-)-deprenyl-responsive diseases, the effect of the drug on cell adhesion, however, is not known. We examined the effect of R-(-)-deprenyl on cell-cell adhesion of neuronal and non-neuronal cells. R-(-)-deprenyl treatment resulted in a cell type- and concentration-dependent increase in cell-cell adhesion of PC12 and NIH3T3 cells at concentrations lower than those required for MAO-B inhibition, while S-(+)-deprenyl was not effective. This acitvity of R-(-)-deprenyl was not prevented by the cytochrome P-450 inhibitor, SKF525A, while deprenyl-N-oxide, a newly described metabolite, also induced an increase in cell-cell adhesion. The effect of R-(-)-deprenyl was not reversible during a 24-hour recovery period. In summary, we described a new, MAO-B independent effect of R-(-)-deprenyl on cell-cell adhesion which can contribute to its neuroprotective function.
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| 5872. |
- Jensen, Ida, et al.
(författare)
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Impact of Magnetic Resonance Imaging Markers on the Diagnostic Performance of the International Parkinson and Movement Disorder Society Multiple System Atrophy Criteria
- 2024
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Ingår i: Movement Disorders. - 0885-3185.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple system atrophy is a neurodegenerative disease with α-synuclein aggregation in glial cytoplasmic inclusions, leading to dysautonomia, parkinsonism, and cerebellar ataxia. Objective: The aim of this study was to validate the accuracy of the International Parkinson and Movement Disorder Society Multiple System Atrophy clinical diagnostic criteria, particularly considering the impact of the newly introduced brain magnetic resonance imaging (MRI) markers. Methods: Diagnostic accuracy of the clinical diagnostic criteria for multiple system atrophy was estimated retrospectively in autopsy-confirmed patients with multiple system atrophy, Parkinson's disease, progressive supranuclear palsy, and corticobasal degeneration. Results: We identified a total of 240 patients. Sensitivity of the clinically probable criteria was moderate at symptom onset but improved with disease duration (year 1: 9%, year 3: 39%, final ante mortem record: 77%), whereas their specificity remained consistently high (99%–100% throughout). Sensitivity of the clinically established criteria was low during the first 3 years (1%–9%), with mild improvement at the final ante mortem record (22%), whereas specificity remained high (99%–100% throughout). When MRI features were excluded from the clinically established criteria, their sensitivity increased considerably (year 1: 3%, year 3: 22%, final ante mortem record: 48%), and their specificity was not compromised (99%–100% throughout). Conclusions: The International Parkinson and Movement Disorder Society multiple system atrophy diagnostic criteria showed consistently high specificity and low to moderate sensitivity throughout the disease course. The MRI markers for the clinically established criteria reduced their sensitivity without improving specificity. Combining clinically probable and clinically established criteria, but disregarding MRI features, yielded the best sensitivity with excellent specificity and may be most appropriate to select patients for therapeutic trials.
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| 5873. |
- Jensen, Kimmo, et al.
(författare)
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GABA Transporter-1 (GAT1) Deficient Mice: Differential Tonic Activation of GABAA versus GABAB Receptors in the Hippocampus.
- 2003
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 90:4, s. 701-2690
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Tidskriftsartikel (refereegranskat)abstract
- After its release from interneurons in the CNS, the major inhibitory neurotransmitter GABA is taken up by GABA transporters (GATs). The predominant neuronal GABA transporter GAT1 is localized in GABAergic axons and nerve terminals, where it is thought to influence GABAergic synaptic transmission, but the details of this regulation are unclear. To address this issue, we have generated a strain of GAT1-deficient mice. We observed a large increase in a tonic postsynaptic hippocampal GABAA receptor-mediated conductance. There was little or no change in the waveform or amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) or miniature IPSCs. In contrast, the frequency of quantal GABA release was one-third of wild type (WT), although the densities of GABAA receptors, GABAB receptors, glutamic acid decarboxylase 65 kDa, and vesicular GAT were unaltered. The GAT1-deficient mice lacked a presynaptic GABAB receptor tone, present in WT mice, which reduces the frequency of spontaneous IPSCs. We conclude that GAT1 deficiency leads to enhanced extracellular GABA levels resulting in an overactivation of GABAA receptors responsible for a postsynaptic tonic conductance. Chronically elevated GABA levels also downregulate phasic GABA release and reduce presynaptic signaling via GABAB receptors thus causing an enhanced tonic and a diminished phasic inhibition.
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| 5874. |
- Jensen, Susanne Sartov, et al.
(författare)
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Parkinsons sjukdom : en utmaning för anestesiologen.
- 2010
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 107:23, s. 1552-1555
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Tidskriftsartikel (refereegranskat)abstract
- Andelen äldre ökar i populationen, och härav följer att ett ökande antal patienter med Parkinsons sjukdom kommer att genomgå operation och anestesi. Parkinsonpatienter behandlas med farmaka som potentiellt interagerar med perioperativt använda läkemedel. Abrupt perioperativ utsättning av antiparkinsonläkemedel ökar risken för försämring av grundsjukdomen och för neurologiska komplikationer ("malingt syndrom"). Parkinsonpatienter har inte sällan autonom dysfunktion, som kan komplicera det perioperativa förloppet. Andra sjukdomar är vanliga i denna patientgrupp. Det är viktigt att planera det perioperativa förloppet noggrant, likaså att fortsätta med antiparkinsonmedicinering under hela det perioperativa förloppet. Det finns idag ingen evidens för att en viss anestesimetod är att föredra framför en annan för denna patientgrupp. Regimen måste individualiseras och hänsyn tas till patientens grundmedicinering, grad av parkinsonkomplikationer och ingreppets natur.
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| 5875. |
- Jeong, D. Y., et al.
(författare)
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Empirical assessment of biases in cerebrospinal fluid biomarkers of alzheimer’s disease : An umbrella review and re-analysis of data from meta-analyses
- 2021
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Ingår i: European Review for Medical and Pharmacological Sciences. - : Verduci Publisher. - 1128-3602. ; 25:3, s. 1536-1547
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: Alzheimer’s disease (AD) is a leading cause of years lived with disability in older age, and several cerebrospinal fluid (CSF) markers have been proposed in individual meta-analyses to be associated with AD but field-wide evaluation and scrutiny of the literature is not available. MATERIALS AND METHODS: We performed an umbrella review for the reported associations between CSF biomarkers and AD. Data from available meta-analyses were reanalyzed using both random and fixed effects models. We also estimated between-study heterogeneity, small-study effects, excess significance, and prediction interval. RESULTS: A total of 38 meta-analyses on CSF markers from 11 eligible articles were identified and reanalyzed. In 14 (36%) of the meta-analyses, the summary estimate and the results of the largest study showed non-concordant results in terms of statistical significance. Large heterogeneity (I2≥75%) was observed in 73% and small-study effects under Egger’s test were shown in 28% of CSF biomarkers. CONCLUSIONS: Our results suggest that there is an excess of statistically significant results and significant biases in the literature of CSF biomarkers for AD. Therefore, the results of CSF biomarkers should be interpreted with caution.
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| 5876. |
- Jeppsson, Anna, et al.
(författare)
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CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics
- 2019
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 90:10, s. 1117-1123
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer's disease-related amyloid β (Aβ) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders. Methods: The study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinson's disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimer's disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ), Aβ species (Aβ38, Aβ40 and Aβ42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1). Results: Patients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, Aβ40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, Aβ40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers. Conclusions: The combination of the CSF biomarkers T-tau, Aβ40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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| 5877. |
- Jepsen, JR, et al.
(författare)
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Diagnostic accuracy of the neurological upper limb examination II: Relation to symptoms of patterns of findings
- 2006
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: In a sample of patients in clinical occupational medicine we have demonstrated that an upper limb neurological examination can reliably identify patterns of findings suggesting upper limb focal neuropathies. This further study aimed at approaching the diagnostic accuracy of the examination. Methods: 82 limbs were semi-quantitatively assessed by two blinded examiners ( strength in 14 individual muscles, sensibility in 7 homonymous territories, and mechanosensitivity at 10 locations along nerves). Based on the topography of nerves and their muscular and sensory innervation we defined 10 neurological patterns each suggesting a localized nerve affliction. Information on complaints ( pain, weakness and/or numbness/tingling) collected by others served as a reference for comparison. The relation between the presence of pattern(s) and complaints was assessed by kappa-statistics. Sensitivity, specificity, and positive/negative predictive values were calculated, and pretest odds were compared to post-test probability. Results: The two examiners identified pattern( s) suggesting focal neuropathy in 34/36 out of 38 symptomatic limbs, respectively (kappa = 0.70/0.75), with agreement in 28 limbs. Out of 44 non-symptomatic limbs the examiners agreed on absence of any pattern in 38 limbs. With concordance between the examiners with regard to the presence or absence of any pattern, the sensitivity, specificity, positive and negative predictive values were 0.73, 0.86, 0.93 and 0.90, respectively. While the pre-test odds for a limb to be symptomatic amounted to 0.46 the post-test probability was 0.81. For each examiner the post-test probability was 0.87 and 0.88, respectively. Conclusion: The improved diagnostic confidence is an indication of one aspect of construct validity of the physical examination. For determination of clinical feasibility of the examination further studies are required, most importantly 1) studies of validity by means of comparison with additional references and 2) studies of the potential benefit that can be attained from its use.
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| 5878. |
- Jergovic, Davor, 1959-, et al.
(författare)
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Changes in a rat facial muscle after facial nerve injury and repair
- 2001
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Ingår i: Muscle and Nerve. - : John Wiley & Sons. - 0148-639X .- 1097-4598. ; 24:9, s. 1202-1212
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Tidskriftsartikel (refereegranskat)abstract
- This study describes changes in a rat facial muscle innervated by the mandibular and buccal facial nerve branches 4 months after nerve injury and repair. The following groups were studied: (A) normal controls; (B) spontaneous reinnervation by collateral or terminal sprouting; (C) reinnervation after surgical repair of the mandibular branch; and (D) chronic denervation. The normal muscle contained 1200 exclusively fast fibers, mainly myosin heavy chain (MyHC) IIB fibers. In group B, fiber number and fiber type proportions were normal. In group C, fiber number was subnormal. Diameters and proportions of MyHC IIA and hybrid fibers were above normal. The proportion of MyHC IIB fibers was subnormal. Immediate and delayed repair gave similar results with respect to the parameters examined. Group D rats underwent severe atrophic and degenerative changes. Hybrid fibers prevailed. These data suggest that spontaneous regeneration of the rat facial nerve is superior to regeneration after surgical repair and that immediacy does not give better results than moderate delay with respect to surgical repair. Long delays are shown to be detrimental.
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| 5879. |
- Jerndal, Mikael, et al.
(författare)
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Systematic review and meta-analysis of the efficacy of basic fibroblast growth factor in experimental stroke
- 2009
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Ingår i: European Stroke conference, Stockholm, Sweden May.
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Konferensbidrag (refereegranskat)abstract
- Background Basic fibroblast growth factor (bFGF) has been shown to have a potent trophic effect on brain neurons, glia and endothelial cells in both in vitro and in vivo studies and is a candidate drug for treatment of ischemic stroke. Any decision to proceed to clinical trials should be based on an unbiased assessment of all available animal data. This assessment should evaluate the efficacy of the drug as well as the characteristics and limits to that efficacy. We use a systematic approach to assess the evidence for protective effects of bFGF in animal models of focal cerebral ischemia. Methods We have performed a systematic review and meta-analysis of studies describing the efficacy of bFGF in animal models of focal cerebral ischemia where outcome was measured as infarct size or neurological score. Study quality was scored against a quality checklist and certain study characteristics were looked at individually. A random effects model was used and the significance level was set to p<0.001 to allow for multiple comparisons. Results Systematic review identified 21 publications of which 20 report infarct size from 520 animals and 10 report neurological score from 223 animals. bFGF reduced infarct size by 25.7% (95% confidence interval 21.7-29.8%) and improved neurological score by 28.1% (23.0-33.2%). Efficacy was higher with intra-arterial administration which showed a reduction of infarct size by 57.6% (33.8-81.3%, p=9.8E-07). Overall study quality was moderate with a median quality score of 6/11, interquartile range 5-7. Studies that performed blinded assessment of outcome showed lesser efficacy on infarct size reduction than those who did not blind, 20.2% (12.2-28.1) compared to 29.4% (26.7-32.1%, p=0.00073). The use of animals with associated comorbidities was rare, with only 4.4% aged animals and no animals with diabetes or hypertension. Aged animals showed lower effect size with only 4.7% reduction of infarct size (-9.0-18.3%, p=1.0E-05). Conclusion Our study shows that bFGF-1 has efficacy in experimental ischemic stroke. The effect of study quality and bias limits the strength of this conclusion. Further research is needed to test the efficacy in animals with associated co morbidities.
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| 5880. |
- Jernerén, Fredrik, et al.
(författare)
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Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer's Disease : The OmegAD Study
- 2019
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 69:1, s. 189-197
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Tidskriftsartikel (refereegranskat)abstract
- Background: Trials of supplementation with omega-3 fatty acids (omega 3-FAs) in patients with mild cognitive impairment or Alzheimer's disease (AD) have produced inconsistent effects on cognitive decline. There is evidence of an interaction between B vitamin status and omega 3-FAs in relation to brain atrophy and cognitive decline.Objective: We investigated whether baseline levels of plasma total homocysteine (tHcy), a marker of B vitamin status, modify the effects of omega 3-FAs supplementation on cognitive performance in moderate AD.Methods: This post hoc analysis of the OmegAD trial included 171 community-based patients with AD (MMSE >= 15): 88 patients received daily doses of 1.7 g docosahexaenoic acid and 0.6 g eicosapentaenoic acid for 6 months. Treatment outcome on cognition was analyzed according to baseline levels of tHcy using a general linear model and ANCOVA.Results: We found significant interactions between omega 3-FA supplementation and tHcy on cognition and clinical stage assessed by MMSE (p = 0.040), global CDR (p = 0.059), and CDRsob (p = 0.023), but not on ADAS-cog (p = 0.649). In patients with tHcy levels <11.7 mu mol/L, omega 3-FA supplementation improved cognitive performance as measured by MMSE (+7.1%, 95% CI: 0.59 to 13.7%, p = 0.033) and clinical status as measured by CDRsob (-22.3%, 95% CI: -5.8 to -38.7%, p = 0.009) compared with placebo.Conclusion: The effect of omega 3-FA supplementation on MMSE and CDR appears to be influenced by baseline tHcy, suggesting that adequate B vitamin status is required to obtain beneficial effects of omega 3-FA on cognition.
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