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Biomedical subjects

Bengt Winblad

Publications and source records attributed to Bengt Winblad.

At least 145 records · Page 8Linked to original sources

Psychological stress and environmental adaptation in enriched vs. impoverished housed rats.

In this study, we report differential behavioural and cognitive effects, as assessed in the open-field and the Morris water maze, following psychological stress in enriched vs. impoverished housed rats. Three stress conditions were evaluated: nonstress, mild stress and powerful stress. Mild stress consisted of exposure to an avoidance box but without shock, while in the powerful stress condition animals were exposed to an electric shock. The results revealed distinct effects in the differentially housed animals. Prior exposure to a mild stress enhanced escape performance in the water maze in enriched but not impoverished animals. However, preexposure to powerful stress negatively affected animals from both housing conditions in the water maze task, but with the enriched animals less affected than impoverished animals. In the open-field test, stress preexposure reduced locomotion counts in both the differentially housed animals. In addition, the results showed that the enrichment effect on emotional reactivity in the open-field is long-lasting and persists even after extensive training and housing in standard laboratory conditions. The results are discussed in relation to the nature of the behavioural and learning differences between the differentially housed animals.

Animals↗

Environmental influences on brain neurotrophins in rats.

Environmental factors can have profound influences on the brain. Enriching environments with physical, social and sensory stimuli are now established to be beneficial to brain development and ageing. A multitude of responses from cellular and molecular mechanisms to macroscopic changes in neural morphology and neurogenesis have been considered in the context for evidences that environmental inputs can regulate brain plasticity in the rat at all stages of life. Data from our laboratory have revealed that enriched environment increased nerve growth factor (NGF) gene expression and protein levels in the hippocampus, and this may contribute to events underlying environmentally induced neural plasticity. Because neurotrophic factors are essential for neural development and survival, they are likely to be involved in the cerebral consequences modified by enriched experiences.

Animals↗

Up-regulation of the inflammatory cytokines IFN-gamma and IL-12 and down-regulation of IL-4 in cerebral cortex regions of APP(SWE) transgenic mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, of which the pathogenesis is thought to involve increased beta-amyloid (Abeta) deposition and abnormal immunological responses. To elucidate the mechanisms involved in Abeta-mediated inflammation, we used immunocytochemistry and in situ hybridization to study the potential role of the cytokines interferon-gamma (IFN-gamma), interleukin (IL)-12 and IL-4 in transgenic mice APP(SWE) (Tg2576) that overexpress the human beta-amyloid precursor protein gene. Cytokine and cytokine mRNA expression was detected in brain sections from cortical regions at various postnatal ages ranging from 3 to 19 months. High levels of IFN-gamma and IL-12 mRNA expression, as well as their protein production, appeared early at 9 months and peaked at 17-19 months in Tg2576 mice. Significantly increased transcripts of IFN-gamma and IL-12 genes were found in the reactive microglia and astrocytes surrounding beta-amyloid deposits. In accordance with the kinetics of mRNA levels, the expression of IFN-gamma and IL-12 at the protein level was positively correlated with age and reached a maximum in 17-19-month-old mice. Both findings suggest a role for the pro-inflammatory cytokines IFN-gamma and IL-12 in early disease development and are consistent with microglial activation related to beta-amyloid formation. In contrast, transcription and production of IL-4 in brain sections was almost undetectable in transgenic mice up to post-natal ages of 17-19 months. These results suggest a major pro-inflammatory role for IL-12 and IFN-gamma in Tg2576 transgenic mice that may provide the association between beta-amyloid plaque formation and microglial and astrocyte activation in these animals. These observations call for further studies on the potential role of anti-inflammatory therapeutic strategies for AD.

Age Factors↗

The impact of somatic and cognitive disorders on the functional status of the elderly.

To estimate the relative effects of coexisting nondementia illnesses on the probability of functional disability, depending on the presence of cognitive impairment or dementia, we used data from the baseline case-control assessment of a longitudinal study of aging and dementia. Our study included 668 subjects (345 nondemented, 98 cognitively impaired, and 225 demented), aged 75 and older. Demented subjects had greater disability prevalence on all specific instrumental activities of daily living (IADL) and activities of daily living (ADL) items than cognitively impaired subjects who, in turn, had greater disability than nondemented subjects. Somatic illnesses were found to be associated with particular tasks in item specific models; decreasing MMSE was strongly associated with the probability of IADL and ADL disability, which increased dramatically in the presence of somatic illnesses among cognitively impaired as well as demented subjects. Attention to illnesses among cognitively impaired and demented people may shed light on remediable factors crucial to their daily functioning.

Activities of Daily Living↗

Alcohol consumption and incidence of dementia in a community sample aged 75 years and older.

To explore the relationship between light to moderate alcohol consumption and risk of dementia and Alzheimer's disease in very old people, a community-based dementia-free cohort (n = 402) was followed for almost 6 years to detect incident dementia using the Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition-Revised criteria. Data from the entire cohort and a subpopulation of those with baseline Mini-Mental State Examination score > or =24 (n = 317) were analyzed with Cox models. In the entire population, light to moderate drinking was significantly associated with a decreased risk of incident dementia and Alzheimer's disease compared with nondrinking (adjusted relative risk 0.5, 95% confidence interval 0.3 to 0.7). In the analysis of the subpopulation, however, the inverse association between light to moderate drinking and risk of incident dementia and Alzheimer's disease was less evident and no longer statistically significant. This study suggested that light to moderate alcohol drinking might protect against dementia and Alzheimer's disease among old people, although the possibility that such an association may be due to information bias cannot be totally ruled out.

Aged↗

Relationship between mercury concentration in blood, cognitive performance, and blood pressure, in an elderly urban population.

Concentration of mercury (Hg) in whole blood in an elderly urban population with a mean age of 87 years was studied in relation to cognitive function, arterial blood pressure (arterial BP), age, gender, body mass index (BMI) and smoking habits. This population-based study consisted of 106 subjects both males and females. Clinical assessment of the subjects included medical and social history, physical and neurologic examination and assessment of cognitive functions with Mini-Mental State Examination (MMSE). Information on use of all potentially antihypertensive drugs was collected. Whole blood from 106 subjects were collected and analysed for mercury by Cold Vapour Atomic Absorption Spectrometry (Milton Ray ASS-CV) with Seronorm Trace Element as matrix matched quality control. Males and females did not differ in blood-mercury (B-Hg) concentrations or in any of the other studied variables. B-Hg concentrations did not differ between smokers and non-smokers. Females were treated more often than males with antihypertensive drugs. There was no relation found between B-Hg concentration and cognitive function, arterial BP, age, gender or BMI. In conclusion, no relations were found between B-Hg concentrations and the studied variables.

Aged↗

Sleep problems in a very old population: drug use and clinical correlates.

BACKGROUND: Complaints of disturbed or dissatisfied sleep are common among older people. This study aimed to evaluate the prevalence of sleep problems in very old persons and its relation to physical and mental health and drug use. METHODS: This is a cross-sectional analysis of sleep problems in a population of old persons living in Stockholm, Sweden. There were 641 subjects aged 81+ years; 77.8% were women, 91.4% were noninstitutionalized, and 68.6% lived alone. All persons underwent a comprehensive medical and psychiatric interview and examination. Sleep problems were assessed using the Clinical Psychopathological Rating Scale (CPRS). Covariates included chronic medical conditions, depression, dementia, pain, self-rated health, activities of daily living, use of hypnotics-sedatives, use of other psychotropic drugs, and use of nonpsychotropic drugs. RESULTS: More than one third of subjects were identified with sleep problems. They were more common among women and persons using a higher number of drugs. Poor self-rated health, depression, and pain were related to the presence of sleep problems. Among persons with sleep problems and depression, only 19.2% used antidepressants, and 46.2% used hypnotics-sedatives. Among persons with sleep problems and pain, 63.2% used analgesics, and 47.0% used hypnotics-sedatives. One or more chronic diseases, use of hypnotics-sedatives, use of other psychotropic drugs, and use of nonpsychotropic drugs were also related to sleep problems. After multivariate analysis, factors significantly related to sleep problems were female gender, depression, pain, and hypnotic-sedative use. CONCLUSIONS: Sleep problems were common in this very old population. These results suggest the importance of carefully assessing an older person's complaints to accurately diagnose and effectively treat sleep problems.

Aged↗

Neutralizing antibodies to IL-18 ameliorate experimental autoimmune neuritis by counter-regulation of autoreactive Th1 responses to peripheral myelin antigen.

Experimental autoimmune neuritis (EAN) is a demyelinating disease of the peripheral nervous system (PNS). This acute inflammatory disease is mediated by CD4+ T cells and bears significant similarities to the Guillain-Barré syndrome of humans. In the present study, we investigated the function of IL-18 in T cell-mediated autoimmunity of EAN in mice induced by P0 peptide 180-199 and Freund's complete adjuvant. Our data indicate that in 2 different therapeutic regimens, anti-IL-18 monoclonal antibody (mAb) effectively ameliorates the clinical and pathological signs of EAN. The suppression is associated with reduced inflammatory cell infiltration into the PNS and an insufficiency of autoreactive Th1 cells, as reflected by a reduced mononuclear cell proliferation and IFN-gamma-secretion in the spleen. Increased numbers of IL-4 expressing cells and decreased numbers of IFN-gamma and TNF-alpha expressing cells were found in the PNS. Our results suggest that shifting the Th1/Th2 balance towards Th2 cells may be one mechanism underlying EAN suppression by anti-IL-18 mAb. In addition, anti-IL-18 mAb treatment reduced anti-P0 peptide 180-199 autoantibody responses, which may also contribute to EAN suppression. We conclude that endogenous IL-18 plays a critical role in the pathogenesis of autoimmune demyelinating disease of the PNS and that IL-18 antagonists may provide a new therapy for these diseases.

Animals↗

Prosthetic crowns and other clinical risk indicators of caries among old-old Swedish adults: findings from the KEOHS Project. Kungsholmen Elders Oral Health Study.

OBJECTIVES: The Kungsholmen Elders Oral Health Study (KEOHS) evaluated the oral health status of generally healthy, community-dwelling persons over the age of 80 living in Kungsholmen, Sweden. This paper explored possible clinical risk indicators of coronal and root caries among the KEOHS subjects. DESIGN: In this cross-sectional study, dentate KEOHS subjects received a caries assessment using defined visual, tactile criteria. SETTING: Examinations were carried out in two local clinics by standardized examiners. SUBJECTS: One hundred twenty-nine dentate persons were examined. MAIN OUTCOME MEASURES: The examination identified decayed and filled surfaces, prosthetic crowns, and missing teeth. RESULTS: More root than coronal surfaces had untreated decay, and secondary root caries contributed the greatest number of decayed surfaces. Ninety percent of the examined dentate subjects had at least one prosthetic crown. Root surfaces exposed to crown margins were more likely to have caries than root surfaces not so exposed, particularly among women. The presence of untreated coronal caries (yes/no) was positively associated with having untreated root caries and an intermediate number (14-20) of teeth, but inversely associated with having 4+ prosthetic crowns. Active root caries (yes/no) was positively associated with having untreated coronal caries, 14-20 teeth, and 4+ prosthetic crowns. Nearly 20% of identified root lesions were present at or below the gingival margin, and most (88%) were secondary caries associated with crown margins (65%) or other restorations (23%). CONCLUSIONS: Our findings suggest that some dental characteristics, including the presence of prosthetic crowns, are risk indicators for the presence of untreated coronal and root caries.

Age Distribution↗

Clinical efficacy of piracetam in cognitive impairment: a meta-analysis.

A meta-analysis has been performed including nineteen double blind, placebo controlled studies with piracetam in patients suffering from dementia or cognitive impairment in the elderly. These studies had as common outcome measure a clinical global impression of change, a measure of clinically meaningful improvement. The meta-analysis of this global outcome followed the methodology set forward by the Cochrane Collaboration. This article describes the studies, the patient populations and the methods of data extraction. The results of the meta-analysis demonstrate a difference between those individuals treated with piracetam and those given placebo, both as significant odds ratio and as a favourable number needed to treat. While there may be problems in meta-analyses and the interpretation of the statistical results, the results of this analysis provide compelling evidence for the global efficacy of piracetam in a diverse group of older subjects with cognitive impairment.

Aged↗

Differential evolution of cognitive impairment in nondemented older persons: results from the Kungsholmen Project.

OBJECTIVE: This study was a prospective, population-based examination of the evolution of cognitive impairment, no dementia (CIND). METHOD: Subjects 75 years old or older living in Stockholm were assessed at baseline and 3 and 6 years later. The severity of CIND was based on age- and education-specific norms on the Mini-Mental State Examination and was classified as mild (N=212), moderate (N=96), or severe (N=57). Mortality, progression to dementia (DSM-III-R), cognitive stability, and cognitive improvement were studied as main outcomes. RESULTS: Of the individuals with mild CIND, 63 (34%) died, 65 (35%) progressed to dementia, 21 (11%) remained stable, and 46 (25%) improved between baseline and first follow-up. The relative risks of progressing to dementia by first follow-up in the subjects with mild, moderate, and severe CIND were 3.6, 5.4, and 7.0, respectively. The relative risk of death decreased with increasing severity of impairment. Individuals who improved at first follow-up did not have a significantly higher risk of later progressing to dementia than subjects who had never been impaired (relative risk=1.4). The absence of a subjective memory complaint predicted improvement (odds ratio=5.4). CONCLUSIONS: CIND is a heterogeneous condition: similar proportions of subjects progress to dementia, death, and cognitive improvement over 3 years. There is no increased future risk of progressing to dementia in CIND subjects who improve during that period.

Age Factors↗

Assessment of Health Economics in Alzheimer's Disease (AHEAD): treatment with galantamine in Sweden.

BACKGROUND: Like other developed countries with aging populations, Sweden is expecting large increases in the prevalence of Alzheimer's disease and corresponding escalations in the cost of care for patients with this disease. Galantamine, a new acetylcholinesterase inhibitor and nicotinic modulator, has proved effective in managing patients with Alzheimer's disease in clinical trials. OBJECTIVE: To estimate the long-term health and economic impact of galantamine from the perspective of the public health payer in Sweden. DESIGN AND SETTING: The Assessment of Health Economics in Alzheimer's Disease (AHEAD) model compares galantamine treatment with no pharmacologic treatment. It consists of a module based on trial data followed by a projection module that uses the trial results to predict the time until patients require full-time care (FTC) or until their death. Forecasts were made for up to 10 years. The model was customised to Sweden by using Swedish resource use profiles obtained from the literature. RESULTS: Galantamine is predicted to reduce the time patients require FTC by almost 10%. Approximately 5.6 patients with mild-to-moderate disease would need to be treated to avoid one year of FTC. This would result in savings averaging 27 436 Swedish kronas (SEK) [3131 euros (EUR)] per patient over 10 years (1998 values). To avoid one year of FTC, 3.9 patients with moderate disease would need to be treated, with savings averaging SEK49 019 (EUR 5594) per patient over 10.5 years. Sensitivity analyses of key parameters, such as proportion of patients needing FTC treated in the community, cost of care in an institution, cost of FTC care in the community, the price of galantamine, and the discount rate, found savings with galantamine would occur under most circumstances. CONCLUSION: Galantamine can increase the time before patients require FTC, and may also lead to savings as treatment costs are offset by reductions in other healthcare expenditures and the costs associated with FTC.

Aged↗

Dental caries in persons over the age of 80 living in Kungsholmen, Sweden: findings from the KEOHS project.

OBJECTIVES: The Kungsholmen Elders Oral Health Study (KEOHS) evaluated the oral health status of generally healthy, community-dwelling persons over the age of 80 living in Kungsholmen, an area in central Stockholm. This paper reports findings regarding the prevalence and severity of dental caries among the dentate participants. BASIC RESEARCH DESIGN: Caries examinations were conducted on eligible persons participating in the Kungsholmen Project, an ongoing, longitudinal study of older adults. SETTING: Caries examinations were carried out between 1994 and 1996 at two local clinics by three standardised examiners using defined visual, tactile criteria. PARTICIPANTS: Among 296 potentially eligible participants, 159 were examined, and a total of 129 had at least one tooth. MAIN OUTCOME MEASURES: The caries examination identified decayed and filled surfaces and missing teeth. RESULTS: Of the dentate subjects examined, 80% had teeth in both arches; 98% had at least one coronal filling; 81% had one or more restored root surfaces. Depending upon age and gender, between 36% and 56% of those examined had untreated coronal caries, and between 54% and 75% had untreated root caries. CONCLUSIONS: These findings document the substantial and ongoing impact of dental caries in a sample of generally healthy, community-dwelling older adults and underscore the importance of continued caries prevention and treatment in the aged.

Age Factors↗

Localization of active forms of C-jun kinase (JNK) and p38 kinase in Alzheimer's disease brains at different stages of neurofibrillary degeneration.

The principal protein component of paired helical filaments (PHFs) in Alzheimer disease is abnormally hyperphosphorylated tau (PHF-tau). The stress activated protein kinases JNK and p38 have been shown to phosphorylate tau at some sites only seen in PHF-tau. If JNK and p38 are involved in the abnormal hyperphosphorylation of tau, they should be activated in neurons undergoing neurofibrillary degeneration. In the present study, we determined the intracellular and regional distribution of the active forms of JNK and p38 kinase in entorhinal, hippocampal, and temporal cortices of brains staged for neurofibrillary changes according to Braak and Braak. Neurons with tangle-like inclusions positive for active forms of JNK and p38 kinase were found to appear first in the Pre-alpha layer of the entorhinal cortex, and then extend into other brain regions co-incident with the progressive sequence of neurofibrillary changes. The intraneuronal accumulation of active forms of JNK and p38 kinase apeared to precede the deposition of amyloid in the extracellular space. These data indicate that increased activation of the stress related kinases JNK and p38 occurs very early in the disease and might be involved in the intraneuronal protein phosphorylation/dephosphorylation imbalance that leads to neurofibrillary degeneration in Alzheimer disease.

Journal Article↗

The number of neurons in the inferior olivary nucleus in Alzheimer's disease and normal aging: A stereological study using the optical fractionator.

The nuclei of the olivary complex are involved in regulating motor movements and in motor learning. Aging is characterized by a progressive accumulation of lipofuscin while the number of olivary neurons is unchanged. It is not known whether neuronal loss occurs in the olivary nucleus during Alzheimer's disease (AD). The aim of this study was to estimate the total number of neurons in the principal olivary nucleus (PO) in AD and control brains using an optimized design for sampling and an unbiased stereological method called the optical fractionator. This study was based on 13 control (mean age =57 y, range 17-95 y) and 16 AD brains (mean age = 86 y, range 67-93 y). Using paraffin-embedded, Nissl-stained sections for quantification, we found a significant difference between the mean values (mean+/-SD) of the AD group vs. aged-matched controls (4.3x10^5+/-1.1 vs. 6.53x10^5+/-1.39 p<0,003). There was no significant difference between younger controls vs. older controls (7.1x10^5+/-1.5 vs. 6.5x10^5+/-1.4 p=0.76). While there was no neuronal loss in normal aging, in AD the PO is characterized by a significant neuronal loss up to 34%. can occur in regions devoid of neurofibrillary changes.

Journal Article↗

Blood pressure and dementia in persons 75+ years old: 3-year follow-up results from the Kungsholmen Project.

A community cohort of 1270 non-demented 75+ years old persons was followed to evaluate the influence of blood pressure on incidence of dementia. Two hundred and eighteen dementia cases were detected during an average of three years of follow-up. Subjects with baseline systolic pressure >/= 180 mm Hg had an age- and gender-adjusted relative risk (RR) of 1.6 (95% to persons with systolic pressure of 141-160 mm Hg. This association persisted, although not statistically significant, when education, vascular diseases, and antihypertensive drug use were entered in the model (RR = 1.4; 95% systolic pressure were not related to dementia incidence. However, individuals with a decrease of 5--19 mm Hg and >/= 20 mm Hg in systolic pressure from baseline to follow-up had a RR of 1.8 (95% 2.6) and 2.5 (95% also found in subjects with diastolic pressure reduction. In conclusion, our findings support an association between high systolic pressure and increased risk of dementia, whereas blood pressure reduction may be secondary to the dementia process itself.

Journal Article↗

Human brain metabolism of morphine and naloxone.

The glucuronidation of morphine and naloxone was investigated in several regions of the human brain. Post-mortem brain tissue specimens were obtained from 19 patients 15 of whom had had cancer. With a few exceptions, all cancer patients had been treated with opiates during the terminal stage of their life. The glucuronide formation of morphine and naloxone was studied in vitro after incubation of the brain microsomal fraction with the substrate and uridine diphosphate glucuronic acid (UDPGA). The glucuronides were analyzed by high performance liquid chromatography. Glucuronidation of morphine and naloxone was catalyzed in 6 of the 19 investigated tissue specimens. The rate of formation of naloxone-3-glucuronide (N3G) exceeded that of the morphine-3-glucuronide (M3G). Morphine-6-glucuronide formation was found in only 2 specimens, in which the formation rate was 10% of the formation rate of M3G. When morphine and naloxone were present simultaneously at equal concentrations (3 mM), the N3G/M3G formation rate ratio increased compared to that when the 2 substrates were incubated one by one. Our findings are interesting from a clinical point of view since the pathways studied represent both bioactivation and inactivation steps in the metabolism of opioids.

Adult↗