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- von Euler, Mia, 1967-, et al.
(författare)
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Inhalation of low concentrations of toluene induces persistent effects on a learning retention task, beam-walk performance, and cerebrocortical size in the rat
- 2000
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Ingår i: Experimental Neurology. - New York, USA : Academic Press. - 0014-4886 .- 1090-2430. ; 163:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The organic solvent toluene is widely used in industry. The threshold limit value for extended occupational exposure to toluene is presently set to 200 ppm in the United States. We have investigated the effect of an inhalation exposure of 80 ppm for 4 weeks (6 h/day, 5 days/week), followed by a postexposure period of at least 4 weeks, on behavior and brain features in the rat. Toluene exposure appeared to affect spatial memory, since toluene-exposed rats showed a longer time in the correct quadrant in a Morris swim maze. This effect may indicate that the exposed rats used their praxis strategy longer before they started to look for the platform elsewhere. Toluene-exposed rats showed trends for increases in both locomotion and rearing behaviors and a significantly reduced beam-walk performance. The area of the cerebral cortex, especially the parietal cortex, was decreased by 6-10% in toluene-exposed rats, as shown by magnetic resonance imaging of living rats and autoradiograms of frozen brain sections. The K(D) and B(max) values of the dopamine D(3) agonist [(3)H]PD 128907 were not affected by toluene, as measured in caudate-putamen and subcortical limbic area using biochemical receptor binding assays and in caudate-putamen and islands of Calleja using quantitative receptor autoradiography. Hence, previously demonstrated persistent effects by toluene on the binding characteristics of radioligands binding to both D(2) and D(3) receptors seem to indicate a persistent effect of toluene selectively on dopamine D(2) receptors. Taken together, the present results indicate that exposure to low concentrations of toluene leads to persistent effects on cognitive, neurological, and brain-structural properties in the rat.
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- Hillefors, M., et al.
(författare)
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Prominent binding of the dopamine D3 agonist [3H]PD 128907 in the caudate-putamen of the adult rat
- 1999
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 822:1-2, s. 126-131
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Tidskriftsartikel (refereegranskat)abstract
- We have analyzed the binding properties of the selective D3 receptor agonist [3H]PD 128907 in 120 days old rats. In tissue sections, we found high numbers of binding sites for [3H]PD 128907 both in the islands of Calleja and the caudate-putamen (Bmax values being 500 and 1000 fmol/mg protein, respectively). The KD values were higher in the caudate-putamen than in the islands of Calleja. Similar regional differences in Bmax and KD values were observed in membranes from the caudate-putamen and the subcortical limbic region. The distribution of [3H]PD 128907 in adult rats is markedly different from that observed in young rats. Taken together, the present results suggest a prominent presence of D3 receptors in the caudate-putamen of adult, but not young, rats. Hence, these findings may have important physiological, pathophysiological, and clinical implications.
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- von Euler, Mia, 1967-, et al.
(författare)
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No protective effect of the NMDA antagonist memantine in experimental spinal cord injuries
- 1997
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Ingår i: Journal of Neurotrauma. - New York, USA : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 14:1, s. 53-61
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the effect of memantine, a clinically used NMDA receptor antagonist, in two experimental animals models of spinal cord injury. The lesions were laser-induced photothrombosis to induce focal spinal cord ischemia and clip compression to mimic traumatic spinal cord injury. Pre- or posttreatment of rats with a dose of memantine (20 mg/kg ip) previously shown to be neuroprotective in cerebral ischemia, failed to affect both the neurological and morphological outcome of ischemic spinal cord injury. Likewise, memantine had no effects on neurological and morphological outcome after experimental traumatic injury. In view of the regional heterogeneity of NMDA receptors, the affinity of memantine for spinal cord NMDA receptors was also determined by studying displacement of [3H] (+)-5-methyl-10,11-dihydro-5-H-dibenzo[a,d]cyclohepten-5-10-imine (MK-801) to rat and human spinal cord homogenates. We found that memantine had an affinity for NMDA receptors in the spinal cord (Ki = 0.58 microM) that was significantly lower compared to that of the cerebral cortex (Ki = 0.23 microM) and that the affinity for NMDA receptors in human spinal cord was even lower. We conclude that in view of available data, memantine should not be chosen for clinical studies on neuroprotection in spinal cord injuries and that the lack of protective effect is most likely due to insufficient affinity of memantine for spinal cord NMDA receptors.
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- Yanes, M., et al.
(författare)
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Antireflux surgery and risk of lung cancer by histological type in a multinational cohort study
- 2020
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 138, s. 80-88
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Airway micro-aspiration might contribute to the proposed associations between gastroesophageal reflux disease (GERD) and some lung diseases, including lung cancer. This study aimed to examine the hypothesis that antireflux surgery decreases the risk of small cell carcinoma, squamous cell carcinoma and adenocarcinoma of the lung differently depending on their location in relation to micro-aspiration. Methods: Population-based cohort study including patients having undergone antireflux surgery during 1980–2014 in Denmark, Finland, Iceland, Norway or Sweden. Patients having undergone antireflux surgery were compared with two groups: 1) the corresponding background population, by calculating standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) and 2) non-operated GERD-patients, by calculating hazard ratios (HRs) with 95% CIs using multivariable Cox regression with adjustment for sex, age, calendar period, country, chronic obstructive pulmonary disease and obesity diagnosis or type 2 diabetes. Results: Among all 812,617 GERD-patients, 46,996 (5.8%) had undergone antireflux surgery. The SIRs were statistically significantly decreased for small cell carcinoma (SIR = 0.57, 95% CI 0.41–0.77) and squamous cell carcinoma (SIR = 0.75, 95% CI 0.60–0.92), but not for adenocarcinoma of the lung (SIR = 0.90, 95% CI 0.76–1.06). The HRs were also below unity for small cell carcinoma (HR = 0.63, 95% CI 0.44–0.90) and squamous cell carcinoma (HR = 0.80, 95% CI 0.62–1.03), but not for adenocarcinoma of the lung (HR = 1.03, 95% CI 0.84–1.26). Analyses restricted to patients with objective GERD (reflux oesophagitis or Barrett's oesophagus) showed similar results. Conclusions: This all-Nordic study indicates that patients who undergo antireflux surgery are at decreased risk of small cell carcinoma and squamous cell carcinoma of the lung, but not of adenocarcinoma of the lung. © 2020 The Author(s)
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- Yanes, M, et al.
(författare)
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Survival after antireflux surgery versus medication in patients with reflux oesophagitis or Barrett's oesophagus : multinational cohort study
- 2021
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Ingår i: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 108:7, s. 864-870
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim was to examine the hypothesis that antireflux surgery with fundoplication improves long-term survival compared with antireflux medication in patients with reflux oesophagitis or Barrett's oesophagus.Method: Individuals aged between 18 and 70 years with reflux oesophagitis or Barrett's oesophagus (intestinal metaplasia) documented from in-hospital and specialized outpatient care were selected from national patient registries in Denmark, Finland, Iceland, and Sweden from 1980 to 2014. The study investigated all-cause mortality and disease-specific mortality, comparing patients who had undergone open or laparoscopic antireflux surgery with fundoplication versus those using antireflux medication. Multivariable Cox regression analysis was used to estimate hazard ratios (HRs) with 95 per cent confidence intervals for all-cause mortality and disease-specific mortality, adjusted for sex, age, calendar period, country, and co-morbidity.Results: Some 240 226 patients with reflux oesophagitis or Barrett's oesophagus were included, of whom 33 904 (14.1 per cent) underwent antireflux surgery. The risk of all-cause mortality was lower after antireflux surgery than with use of medication (HR 0.61, 95 per cent c.i. 0.58 to 0.63), and lower after laparoscopic (HR 0.56, 0.52 to 0.60) than open (HR 0.80, 0.70 to 0.91) surgery. After antireflux surgery, mortality was decreased from cardiovascular disease (HR 0.58, 0.55 to 0.61), respiratory disease (HR 0.62, 0.57 to 0.66), laryngeal or pharyngeal cancer (HR 0.35, 0.19 to 0.65), and lung cancer (HR 0.67, 0.58 to 0.80), but not from oesophageal cancer (HR 1.05, 0.87 to 1.28), compared with medication, The decreased mortality rates generally remained over time.Cconclusion: In patients with reflux oesophagitis or Barrett's oesophagus, antireflux surgery is associated with lower mortality from all causes, cardiovascular disease, respiratory disease, laryngeal or pharyngeal cancer, and lung cancer, but not from oesophageal cancer, compared with antireflux medication.
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