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Lars Iversen

Publications and source records attributed to Lars Iversen.

30 records · Page 2Linked to original sources
PubMed2003

Tracking drinking behaviour from age 15-19 years.

AIMS: The aim of this paper was to assess (1) changes in drinking behaviour over time among Danish adolescents and (2) use of which alcoholic beverages and what drinking patterns would have the strongest predictive effect on later alcohol consumption. DESIGN, SETTING, PARTICIPANTS: The population was a random sample of 15-year-olds (baseline 1990, response rate 86%, n= 847) with a first follow-up 4 years later (response rate 85%, n= 729). MEASUREMENTS: Alcohol intake was assessed by experience of drunkenness, quantity and frequency of consumption. Thresholds recommended by the Danish National Board of Health were used to discriminate high from low intake. FINDINGS: At 19 years of age at least 80% drank alcohol monthly, and 24% of the men and 11% of the women had an alcohol intake above the recommended national limits, i.e. 21 weekly units of alcohol for men and 14 for women. Consumption of alcoholic beverages at age 15 increased the risk of drinking alcohol weekly at the age of 19 [odds ratio (OR)-values from 1.11 to 3.53]. Drunkenness among the 15-year-old boys and the use of spirits of the 15-year-old girls showed the strongest predictive relationship with excessive consumption at age 19 [OR = 2.44, confidence interval (CI): 1.38-4.29, respectively, OR = 1.97, CI: 1.15-3.38]. CONCLUSIONS: Alcohol consumption as early as the age of 15 predicted weekly alcohol consumption and alcohol intake exceeding the recommended amount 4 years later. Young teenagers' high alcohol consumption was not just a passing phenomenon. It was a behaviour that tracked into young adulthood, leaving the adolescents at increased risk of being long-term, large-scale consumers.

Adolescent↗
PubMed2003

1alpha,25-dihydroxyvitamin D3 stimulates activator protein 1 DNA-binding activity by a phosphatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1-dependent increase in c-Fos, Fra1, and c-Jun expression in human keratinocytes.

1alpha,25-Dihydroxyvitamin D3 added to human keratinocytes increases differentiation through an activation of the transcription factor activator protein 1. We have previously reported that the 1alpha,25-dihydroxyvitamin D3-induced increase of activator protein 1 DNA binding activity is mediated by a protein kinase C-independent mechanism. The purpose of this study was to investigate further the mechanisms by which 1alpha,25-dihydroxyvitamin D3 modulates activator protein 1 DNA binding activity in cultured normal human keratinocytes. Western blotting experiments revealed that 1alpha,25-dihydroxyvitamin D3 caused a rapid and transient activation of the mitogen-activated protein kinases, extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1. 1alpha,25-Dihydroxyvitamin D3 also enhanced the expression of the activator protein 1 subunits, c-Fos, Fra1, and c-Jun as determined by northern and western blotting. The 1alpha,25-dihydroxyvitamin D3-induced activator protein 1 DNA binding activity was completely blocked by the MEK inhibitor PD 98059 indicating that the MEK/extracellular signal regulated kinase pathway is involved in the activation of activator protein 1. Transfection experiments showed that 1alpha,25-dihydroxyvitamin D3 also increased the activator protein 1-dependent transactivation, which was completely blocked by expression of a dominant negative Ras, suggesting that the 1alpha,25-dihydroxyvitamin D3-induced activator protein 1 activity involves Ras-dependent signaling. Furthermore, preincubation of the keratinocytes with the specific phosphatidylinositol 3-kinase inhibitors, Wortmannin and LY294002, demonstrated that the 1alpha,25-dihydroxyvitamin D3-induced activation of extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1 required phosphatidylinositol 3-kinase activity. Finally, preincubation of keratinocytes with a polyclonal antibody against the membrane receptor annexin II, blocked the 1alpha,25-dihydroxyvitamin D3-induced activation of extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1. Taken together, our results indicate that 1alpha,25-dihydroxyvitamin D3, via binding to the membrane receptor annexin II, induces activation of the phos-phatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1 signal transduction pathway resulting in increased expression of c-Fos, Fra1, and c-Jun, and subsequently increased activator protein 1 DNA binding activity and gene transcription.

Adult↗
PubMed2003

Expression and localization of peroxisome proliferator-activated receptors and nuclear factor kappaB in normal and lesional psoriatic skin.

Abnormal epidermal proliferation and differentiation characterize the inflammatory skin disease psoriasis. Here we demonstrate that expression of PPARdelta mRNA and protein is markedly upregulated in psoriatic lesions and that lipoxygenase products accumulating in psoriatic lesions are potent activators of PPARdelta. The expression levels of NF-kappaB p50 and p65 were not significantly altered in lesional compared with nonlesional psoriatic skin. In the basal layer of normal epidermis both p50 and p65 were sequestered in the cytoplasm, whereas p50, but not p65, localized to nuclei in the suprabasal layers, and this distribution was maintained in lesional psoriatic skin. In normal human keratinocytes PPAR agonists neither impaired IL-1beta-induced translocation of p65 nor IL-1beta-induced NF-kappaB DNA binding. We show that PPARdelta physically interacts with the N-terminal Rel homology domain of p65. Irrespective of the presence of agonists none of the PPAR subtypes decreased p65-mediated transactivation in keratinocytes. In contrast p65, but not p50, was a potent repressor of PPAR-mediated transactivation. The p65-dependent repression of PPARdelta- but not PPARalpha- or PPARgamma-mediated transactivation was partially relieved by forced expression of the coactivators p300 or CBP. We suggest that deficient NF-kappaB activation in chronic psoriatic plaques permitting unabated PPARdelta-mediated transactivation contributes to the pathologic phenotype of psoriasis.

CD36 Antigens↗
PubMed2003

How does individual smoking behaviour among hospital staff influence their knowledge of the health consequences of smoking?

AIMS: This study examined associations between individual smoking habits among hospital staff and their knowledge of the health consequences of smoking and passive smoking. The a priori hypothesis was a higher level of knowledge among non-smokers compared with smokers. METHODS: A survey was undertaken, based on self-administered questionnaires at a Danish hospital (Frederikssund Hospital) in the Copenhagen area. Descriptive statistics, chi-square test and multiple logistic regression analyses were used. A backward stepwise elimination of variables at a 5% level of significance was performed and 95% confidence intervals were calculated. Main outcome measures were knowledge of the health consequences of smoking, passive smoking and other lifestyle factors. RESULTS: A total of 445 of 487 employees (91%) from all professional groups returned the questionnaire. Compared with ex- and never smokers, smokers systematically underestimate the health consequences of smoking and passive smoking independent of profession, department, sex, and age. There is no consistent association between knowledge of the health consequences of smoking and profession and department. There are significant inverse associations between smoking and knowledge of the health effects of excess use of alcohol and lack of physical activity. CONCLUSION: Individual smoking habits among hospital staff strongly influence smoking-related knowledge. No other variables are of consistent importance. These findings are supported by the literature. The validity of the study is good, but a similar study in a bigger population would strengthen the evidence.

Adult↗
PubMed2002

[Impact of a 10-year nation-wide campaign on knowledge of sensible drinking limits in Denmark].

INTRODUCTION: In Great Britain and in Denmark, strong efforts have been made to influence knowledge on the upper threshold of hazardous drinking. In Denmark, a campaign has been repeated every week 40 from 1990 to 2001 with information on the sensible drinking limits of 21 drinks per week for men and 14 drinks per week for women. The aim of this study was to examine the effect of this ongoing campaign on the level of knowledge of sensible drinking limits for men and women. MATERIAL AND METHODS: Every year from 1994 to 1999, random representative samples of 1,030 adult Danes were interviewed on the telephone. RESULTS: Our main finding was that the level of knowledge of sensible drinking limits for own sex increased in all subsets of the population throughout the period. However, at the end of the study period (1999), a total of 80% of highly educated young (18-25 years of age) men knew sensible drinking limits for own sex, while only 35% of uneducated older (more than 65 years old) men had knowledge on sensible drinking limits. The proportions were similar among women: Subjects admitting an intake higher than sensible for own sex, i.e. 21 and 14 drinks per week, respectively, had the highest knowledge of these drinking limits. DISCUSSION: We conclude that public health campaigns, such as the sensible drinking limit campaign, certainly has an impact on the level of awareness in the general population. Furthermore, those drinking more than 21 and 14 drinks per week, respectively, are reached by these campaigns.

Adult↗
PubMed2002

[The relation between life style, socioeconomic factors, social networks and suboptimal self-assessed health].

INTRODUCTION: The aim of the present study was to assess the relation between these life-style factors and suboptimal self-reported health. METHODS: A cross-sectional study was carried out on a random sample of 12,040 men and women from Copenhagen, who had answered a questionnaire regarding smoking, alcohol intake, physical activity, socio-economic status, social network, and self-perceived health. RESULTS: Smoking, high alcohol intake, and physical inactivity are strongly associated with a suboptimal self-reported health. DISCUSSION: The assumption of a correlation between a high quality of life and a shorter life cannot be confirmed by this study.

Adult↗
PubMed1999

Biological variation of canine serum thyrotropin (TSH) concentration.

The aim of the present study was to estimate the between-dog, within-dog and analytical components of variance for serum thyrotropin (TSH) in healthy dogs, and to use these components of variance to 1) estimate the critical difference for significance between serial results; 2) assess the utility of the conventional population-based reference interval; 3) set a desirable performance standard for analytical imprecision; and 4) estimate the number of samples required for determination of the true mean value for an individual dog. Using the Immulite test system, TSH was measured in serum samples collected weekly for five weeks from eight clinically healthy dogs. Results were subjected to nested analysis of variance. Between-dog variation was 43.6%, within-dog variation was 13.6%, analytical variation was 8.8%, the one-sided critical difference was 37.8%, the index of individuality was 0.4, the maximum allowable analytical imprecision was 6.8%, and the number of samples required to determine the true mean value in a single dog was 40. In practical terms, the present study indicated that the analytical imprecision of canine serum TSH measurement should be < 7%, and that comparing a single serum TSH measurement from an individual dog to the conventional population-based reference range may be too insensitive to detect small but important changes in the serum TSH level of that particular dog. In addition, when treating a hypothyroid dog, serum TSH, measured on a weekly basis, should decrease by at least one-third before any effect of exogenous thyroxine supplementation can be said to have influenced the serum TSH level.

Journal Article↗
PubMed1999

Evaluation of analytical performance assisted by total error criteria of a commercial enzyme immunometric assay for canine serum thyrotropin.

The aim of the present study was to evaluate analytical performance using total error criteria of a commercial enzyme immunometric assay for the determination of endogenous canine thyrotropin (TSH). The allowable total error for this assay (22.6%) was estimated using previously reported data on biological variation. Inaccuracy and imprecision of the assay (0% and 5.7% for the low control material; 6.8% and 3.0% for the high control material) were estimated by measuring the same lot of control material for 21 consecutive weeks, during which time the assay was considered stable and in control. Analytical performance was assessed using a MEDx chart, a graphical tool for comparing inaccuracy and imprecision, with an analytical quality requirement stated in the form of allowable total error. The results of the present study showed that the canine TSH assay had good to excellent analytical performance.

Journal Article↗
PubMedDate not supplied

Non-linear mixed effects modeling of sparse concentration data from rats: application to a glycogen phosphorylase inhibitor.

We investigated the use of non-linear mixed effects modeling in two preclinical studies of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB). In a 28-day repeated-dose toxicity study rats were dosed once daily p.o. with 0, 20, 45, 100, or 470 mg/kg of DAB in aqueous solutions by oral gavage. Three blood samples were obtained from each animal using a staggered sampling scheme. During the cause of model development, data were included from a safety pharmacological cardiovascular study, in which rats were dosed once orally with 0, 4, 40, or 400 mg/kg of DAB thereby enabling an extension of the dose range of the model. DAB was assayed in plasma using a validated LC/MS/MS method. Non-linear mixed effects modeling was performed using the software NONMEM. The covariate analysis comprised dose, sex and time. Exposure results (Cmax, AUC) obtained by mixed effects modeling were compared to results from noncompartmental analysis using naïve pooling of data. The final model was a one-compartment model with first order absorption and a saturation-like dose dependent increase of the (oral) clearance (CL/f) and volume of distribution (V/f). Furthermore, V/f increased (by 55%) from Day 1 to Day 28. The dose dependencies of CL/f and V/f were most likely due to dose dependent decreases of the fraction systemically absorbed (f). The mechanism behind the dose dependencies may be saturation of a (putative) carrier mediated transport or modulation of tight junctions causing a reduced paracellular transport across the intestinal epithelium. Exposure results obtained from the model compared well with results obtained using noncompartmental analysis. An analysis of the data requirements for non-linear mixed effects modeling showed that at least three concentration values per animal were required for model development. We conclude that non-linear mixed effects modeling is feasible even with dose dependent pharmacokinetics in preclinical studies, such as 28-day toxicity studies in rodents. Supplementing data from additional preclinical studies may be required in order to extend the dose range. Non-linear mixed effects models may prove to be valuable tools in early PK and PK-PD modeling during drug development.

Animals↗
PubMedDate not supplied

Cynical hostility, socioeconomic position, health behaviors, and symptom load: a cross-sectional analysis in a Danish population-based study.

OBJECTIVE: To analyze the cross-sectional association between cynical hostility and high symptom load in a Danish population-based study. Furthermore, the aim was to investigate to what extent health risk behaviors mediated this association. METHODS: Data were based on a postal questionnaire in a Danish random sample of 3426 men and 3699 women aged 40 or 50 years. Cynical hostility was measured by the 8-item Cynical Distrust Scale. High symptom load was assessed by physiological and mental symptoms experienced within the last 4 weeks. Confounders were age and socioeconomic position, while potential mediators were alcohol consumption, smoking, physical activity, and BMI. RESULTS: Higher cynical hostility was associated with self-reported symptom load. Health behaviors did not seem to mediate this effect. Socioeconomic position was a strong confounder for the effect on both health and health behaviors. After adjustment the effects of hostility on health remained with odds ratios of 2.1 (1.7-2.6) for women and 2.3 (1.8-2.8) for men. CONCLUSION: After adjustment for socioeconomic position, cynical hostility has an effect on self-reported high symptom load, and this effect is not mediated by health behaviors.

Adult↗
PubMedDate not supplied

Signal transduction pathways in human epidermis.

Cytokines, hormones and other signaling molecules regulate a number of diverse biological processes in the skin including the control of cell growth, differentiation, homeostasis, and various immune functions. This review describes the fundamental concepts of signaling in the cell and we discuss more thoroughly selected signaling pathways important in the skin. Fundamentally cellular signaling can be mediated through two different signaling mechanisms: 1) through binding to a receptor at the outer surface of the cellular-membrane and a subsequent activation of a signal transduction cascade. 2) through binding to nuclear receptors and subsequent regulation of gene-transcription. Changes in the signaling apparatus in the cell play a key role in the pathogenesis of a number of different skin diseases and a better understanding of these different signaling pathways may therefore offer new therapeutic targets.

Epidermis↗