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Biomedical subjects

L Iversen

Publications and source records attributed to L Iversen.

At least 19 recordsLinked to original sources

Phenolic antioxidants attenuate neuronal cell death following uptake of oxidized low-density lipoprotein.

Oxidative stress is implicated in neuronal loss associated with neurodegeneration such as in Parkinson's disease, Alzheimer's disease and age-related cognitive decline. Recent reports indicate that the consumption of flavonoid-rich fruits partly reverses the age-related neuronal and cognitive decline. In this study, cultured striatal neurons were exposed to oxidized lipids in the form of low-density lipoprotein (oxLDL) as a model for the induction of oxidative injury, and the abilities of phenolic antioxidants, flavonoids and hydroxycinnamic acid derivatives, to attenuate this neuronal damage were examined. OxLDL was demonstrated to enter neuronal cells and to be capable of eliciting neurotoxicity in a dose- and time-dependent manner, inducing DNA fragmentation and cell lysis. Flavonoids exert protective effects, which appear to be related to specific structural characteristics, particularly relevant being those defining their reduction potentials and partition coefficients. In summary, these data suggest a possible role for flavonoids in reducing neurodegeneration associated with chronic disorders in which oxidative stress is implicated.

Animals↗

[Active and passive smoking among personnel at the Bispebjerg Hospital 1992-1999].

The purpose of this study was to describe changes in smoking behaviour and exposure to passive smoking among hospital employees at a large Danish University Hospital (Bispebjerg Hospital) from 1992 until 1999 as part of a program toward a smoke-free hospital. The study was based upon three cross-sectional self-administered questionnaires surveys carried out among all employees at the hospital--approximately 4000 persons--in October 1992, April 1997 and April 1999, participation rates being 84, 80 and 76 percent. During the seven year period the smoking rate has decreased from 46% to 32% among male and 40% to 33% among female employees. A decrease in smoking rate was found among all subgroups of employees. Among male employees the rate of heavy smokers has decreased from 25 to 16%, among female employees this decrease is lacking, the rate of heavy smokers being 15% during the whole period. The numbers of employees exposed to passive smoking all day or most of the day has changed from 39% to 25% from 1992 until 1999. Among the smokers 30%--8% of all employees--responded that they would not be able to manage without smoking tobacco during working hours. This answer is most commonly found among heavy smokers, smokers with short or no education and smokers who smoke at any time of day. It is concluded that even though there has been a reduction in the smoking rate, the exposure to passive smoking among employees at the hospital still is unacceptably high. Based upon these results it has been decided that Bispebjerg Hospital is smoke-free for all employees from the 1st of January 2000. There is a need for initiatives for the smokers, who can't manage work without smoking.

Attitude to Health↗

Neurotransmitter transporters: fruitful targets for CNS drug discovery.

More than 20 members have been identified in the neurotransmitter transporter family. These include the cell surface re-uptake mechanisms for monoamine and amino acid neurotransmitters and vesicular transporter mechanisms involved in neurotransmitter storage. The norepinephrine and serotonin re-uptake transporters are key targets for antidepressant drugs. Clinically effective antidepressants include those with selectivity for either NE or serotonin uptake, and compounds with mixed actions. The dopamine transporter plays a key role in mediating the actions of cocaine and the amphetamines and in conferring selectivity on dopamine neurotoxins. The only clinically used compound to come so far from research on amino acid transporters is the antiepileptic drug tiagabine, a GABA uptake inhibitor.

Antidepressive Agents↗

1alpha,25-dihydroxyvitamin D3 induced differentiation of cultured human keratinocytes is accompanied by a PKC-independent regulation of AP-1 DNA binding activity.

1alpha,25(OH)2D3 and its analogs are potent mediators of keratinocyte differentiation in vitro. The precise mechanism of this action is still unknown. The nuclear transcription factor activator protein 1 seems to play an important role in keratinocyte differentiation. The purpose of this study was to investigate the effect of 1alpha,25(OH)2D3 on activator protein 1 DNA binding activity in cultured human keratinocytes. In a time-course study of human keratinocytes incubated with 1alpha,25(OH)2D3 (10-7-10-11 M) a significant dose-dependent increase in activator protein 1 DNA binding activity as determined by electrophoretic mobility shift assay was seen after 36 h. This increase was followed by a significant dose-dependent decrease in activator protein 1 DNA binding activity after 72 h. When differentiation was induced by raising the calcium concentration in the culture medium from 0.09 to 0.3 mM a similar increase in activator protein 1 DNA binding activity was observed after incubation for 48 h. Pharmacologic down-modulation of the protein kinase C activity with GF 109203X reversed the calcium-induced increase in activator protein 1 DNA binding activity and abolished keratinocyte differentiation as determined by a transglutaminase assay. In contrast, activator protein 1 DNA binding activity and keratinocyte differentiation were not affected when protein kinase C activity was down-modulated in the experiments with 1alpha,25(OH)2D3. The activator protein 1 complex in human keratinocytes consists of dimers of Fra-1, Fra-2, c-Jun, JunD, and c-Fos. Our results demonstrate that 1alpha, 25(OH)2D3- and calcium-induced keratinocyte differentiation are accompanied by changes in activator protein 1 DNA binding activity. Protein kinase C activation appears to be essential for the calcium-dependent induction of keratinocyte differentiation, whereas a protein-kinase-C-independent activation of activator protein 1 DNA binding and keratinocyte differentiation is responsible for the 1alpha,25(OH)2D3-induced effects.

Calcitriol↗

Orthodontics at the turn of the century. A discussion of some relevant aspects.

Some changing paradigms, that might influence orthodontics in the future, are being discussed: economic problems related to our welfare systems; development of the media societies; concepts of normality; future changes as regards the type of treatment records; evaluation of treatment outcome; "exaggerated orthodontics?"; orthodontics and facial aesthetics; Newtonian paradigms and scientific revolution; the growth of knowledge; phenomenology; tacit knowledge; decision making.

Esthetics, Dental↗

The long-term biological variability of fasting plasma glucose and serum fructosamine in healthy Beagle dogs.

The aim of this study was to estimate the long-term (month-to-month) between-dog, within-dog and analytical components of variance for fasting plasma glucose and serum fructosamine in healthy dogs to assess the usefulness of a single measurement of these analytes in a single dog. Fasting plasma glucose and serum fructosamine were measured in blood samples collected every month for 9 months from 23 clinically healthy dogs, and the results were subjected to nested analysis of variance. The between-dog variation, the within-dog variation, and the analytical variation were 3.8%, 9.5% and 3.7%, respectively, for plasma glucose and 4.2%, 11.1% and 2.8%, respectively, for serum fructosamine. The maximum allowable analytical imprecision, analytical inaccuracy and difference between analytical methods were 4.8%, 2.6% and 3.2%, respectively, for plasma glucose and 5.6%, 3.0% and 3.7%, respectively, for serum fructosamine. The index of individuality, 2.7 for both analytes, indicated that the test results from single dogs can be compared usefully to the corresponding population-based reference intervals. The number of samples required to estimate the true individual mean value +/-5% for a single dog was 16 for fasting plasma glucose and 20 for serum fructosamine. The one- and two-sided critical differences expressing the difference needed for two serial results from the same dog to be significantly different at a 5% level was 24% and 28%, respectively, for plasma glucose and 27% and 32%, respectively, for serum fructosamine.

Animals↗

Evidence of nuclear PKC/MAP-kinase cascade in guinea pig model of epidermal hyperproliferation.

In order to delineate the biochemical events in the nuclear compartment of an in vivo proliferating epidermis, we produced a model of hyperproliferative epidermis by topical application of docosahexaenoic acid (22:6n-3) on guinea pig skin. Employing this model we demonstrated: (i) that protein kinase C (PKC)-a and atypical PKC-zeta are the two major PKC isozymes in the normal epidermal nuclear membrane, in contrast to PKC-alpha and PKC-beta in the epidermal plasma membrane; (ii) that topical application of docosahexaenoic acid induced epidermal hyperproliferation and enhanced total nuclear PKC, particularly nuclear PKC-alpha and the atypical PKC-zeta isozymes. The increase in the nuclear PKC isozymes paralleled a marked increase in the expression of nuclear mitogen-activated protein-kinase. These data suggest that epidermal hyperproliferative activity is accompanied by the upregulation of nuclear PKC/mitogen-activated protein-kinase signaling pathway.

Animals↗

Development and validation of an improved enzyme-linked immunosorbent assay for the detection of thyroglobulin autoantibodies in canine serum samples.

An enzyme-linked immunosorbent assay to detect thyroglobulin autoantibodies (TGAB) in canine serum was developed and validated. The test result for each sample was derived from the optical density readings (OD) and expressed as an Ab-score(%) calculated from three in-house calibrators. The assay specifically detected TGAB as judged from lack of response in the assay after samples had been incubated with specific antigen. Intra- and interassay coefficients of variation ranged from 2.0-4.9% and 4.6-9.9%, respectively. The detection limit, an Ab-score of 5.6%, was close to the median Ab-score of 10% observed in healthy dogs (n = 132). The median Ab-score of dogs with primary hypothyroidism and lymphocytic thyroiditis (n = 11), skin diseases (n = 35), and non-thyroidal diseases (n = 63) was 340%, 12%, and 8%, respectively. The prevalence of TGAB in hypothyroid dogs with lymphocytic thyroiditis (sensitivity) was 91% (95% confidence limits: 59%-99%). In dogs with dermatological diseases without lymphocytic thyroiditis the prevalence of TGAB was 3% corresponding to a specificity of 97% (95% confidence limit: 85%-100%). In dogs with non-thyroidal diseases and healthy dogs the prevalence of TGAB was 5% and 6%, respectively. The diagnostic accuracy of serum TGAB was evaluated by subjecting the data from 11 dogs with lymphocytic thyroiditis and 35 control dogs without lymphocytic thyroiditis to receiver-operating characteristic curve analysis. The area under the receiver-operating characteristic curve (W = 0.966; 95% confidence limit 87%-100%) was significantly higher than that of a worthless test (0.5) (P < 0.0001), thereby indicating that serum TGAB measurements distinguished between dogs with and without lymphocytic thyroiditis.

Animals↗

Upregulation of nuclear PKC and MAP-kinase during hyperproliferation of guinea pig epidermis: modulation by 13-(S)-hydroxyoctadecadienoic acid (13-HODE).

13-(S)-Hydroxyoctadecadienoic acid (13-HODE), the lipoxygenase metabolite of linoleic acid, has been shown to reverse the epidermal hyperproliferation induced by topical application of docosahexaenoic acid (DNA, 22:6 n-3) on guinea pig skin. Our initial studies demonstrated that 13-HODE exerts a selective inhibition of the membrane-bound PKC-beta activity in the hyperproliferative skin. To delineate the antiproliferative effects of 13-HODE, we investigated the nuclear events associated with this process. Our data demonstrated that the major PKC isozymes in the epidermal nuclear fraction are alpha and zeta. Epidermal hyperproliferation induced by DHA caused an increase in nuclear total PKC and atypical PKC activities, and this was accompanied by an increase in the two nuclear isozymes, alpha and zeta (P < 0.05). This increase was reversed after topical application of 13-HODE. Similarly, 13-HODE suppressed elevated nuclear MAP-kinase. Taken together, these data suggest that nuclear signalling events in the epidermis involve PKC-MAP-kinase pathway.

Animals↗