Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23.

Spinocerebellar ataxias (SCAs) are dominantly inherited neurodegenerative disorders characterized by progressive cerebellar ataxia and dysarthria. We have identified missense mutations in prodynorphin (PDYN) that cause SCA23 in four Dutch families displaying progressive gait and limb ataxia. PDYN is the precursor protein for the opioid neuropeptides, α-neoendorphin, and dynorphins A and B (Dyn A and B).

The effect of substance P1-7 amide on nociceptive threshold in diabetic mice.

We previously demonstrated that intrathecal treatment with substance P metabolite substance P(1-7) induced anti-hyperalgesia in diabetic mice. In the present study, we have used a synthetic analog of this peptide, the substance P(1-7) amide, showing higher binding affinity than the native heptapeptide, for studies of the tail-flick response in diabetic and non-diabetic mice. Intrathecal injection of substance P(1-7) amide produced prolongation of the tail-flick latency in both diabetic and non-diabetic mice, an effect that was more pronounced in diabetic mice than non-diabetic mice.

Allosteric modulation of the NMDA receptor by neurosteroids in rat brain and the impact of long term morphine administration.

This study examined the allosteric modulation of the NMDA receptor by nanomolar concentrations of neurosteroids in rats treated long term with morphine. The neurosteroids dehydroepiandrosterone sulfate (DHEAS), pregnenolone sulfate (PS) and pregnanolone sulfate (3α5βS) are important mediators in the central nervous system. They induce rapid responses by non-classical steroidal mechanisms, e.

Evaluation of disease activity and damage in different subtypes of cutaneous lupus erythematosus using the CLASI.

Background: The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a scoring system for patients with cutaneous lupus erythematosus (CLE) to assess disease activity and damage. Objective  The aim of this study was to evaluate whether the CLASI is a useful instrument which reflects the different subtypes of CLE comparably well in each parameter.

Methods: A total of 50 patients (42 female, 8 male) with different subtypes of CLE, including acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE) and LE tumidus (LET), from the Departments of Dermatology, University of Düsseldorf, Germany, and Danderyd Hospital, Stockholm, Sweden, were evaluated using the CLASI at one time point.

Is there an association between the use of anabolic-androgenic steroids and criminality?

Aims: The aim of this study was to improve our understanding of the proposed association between anabolic-androgenic steroids (AAS) and criminality.

Methods: The study was based on interviews and criminality data involving 32 users of AAS who had sought treatment for AAS-related problems at a psychiatric addiction clinic in Sweden. A score derived from the number of crimes, their level of severity and the relevant time periods was computed to allow comparisons between subgroups sorted according to type and timing of drug use.

Precautions to improve the accuracy of quantitative determinations of biomarkers in clinical diagnostics.

Although protein biomarkers have a great potential as biomarkers for diagnosis of diseases, they are seldom used in hospitals. There are many reasons for this, for instance, the difficulties to (i) find a biomarker for which the concentration in body fluids clearly differs between patients and healthy subjects, (ii) attain purification of the biomarker close to 100%, which is required for production of conventional protein antibodies as well as artificial gel antibodies for selective capture of a biomarker, (iii) design a standard curve for rapid and accurate determination of the concentration of the biomarker in the body fluid because of adsorption of the biomarker onto vials, pipettes, etc., (iv) determine accurately the sample volume delivered by a pipette, (v) avoid polymerization of the biomarker upon storage and to decide whether it is in the form not only of monomers, but also of dimers, trimers, etc.

Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006.

Unlabelled: The risk of ischaemic heart disease (IHD), and in particular myocardial infarction (MI), is increased amongst patients with established rheumatoid arthritis (RA). Few studies have included contemporary patients with RA. We recently reported that the risk of IHD is not elevated before the onset of RA symptoms.

Different SNP combinations in the GCH1 gene and use of labor analgesia.

Background: The aim of this study was to investigate if there is an association between different SNP combinations in the guanosine triphosphate cyclohydrolase (GCH1) gene and a number of pain behavior related outcomes during labor. A population-based sample of pregnant women (n = 814) was recruited at gestational week 18. A plasma sample was collected from each subject.

Plasma levels of beta-endorphin during pregnancy and use of labor analgesia.

Beta-endorphins are endogenous opioid substances produced by the pituitary gland and placenta. The aims of this project were to longitudinally follow plasma levels of beta-endorphin during pregnancy in women with a healthy pregnancy and to investigate whether plasma levels of beta-endorphin in late pregnancy are associated with need for additional pain medication beyond nitrous oxide during labor. Plasma samples from 45 women were collected at gestational weeks 10, 25, 28, 33 and 37, and beta-endorphin was analyzed by radioimmunoassay (RIA).

A database analysis of cutaneous lupus erythematosus with the EUSCLE Core Set Questionnaire.

The aim of this study was to determine whether the Core Set Questionnaire developed recently by the European Society of Cutaneous Lupus Erythematosus (EUSCLE) is a useful tool to evaluate clinical features and therapeutic strategies in cutaneous lupus erythematosus. Disease characteristics were analysed in 50 patients with different subtypes of cutaneous lupus erythematosus from two European centres (Germany and Sweden). Mean age at onset of disease was 42.

Cutaneous manifestations and serological findings in 260 patients with systemic lupus erythematosus.

The prevalence and prognostic value of cutaneous manifestations in patients with systemic lupus erythematosus (SLE) is not clear due to a lack of distinct criteria. Our aim was to investigate the prevalence of cutaneous manifestations in SLE patients according to strict dermatological classification, compare the results with other studies and to assess differences in serological markers between patients with and without cutaneous lupus erythematosus (CLE). Secondary aims were to investigate the validity of the criteria 'malar rash' and 'photosensitivity' for SLE diagnosis.

Selective angiotensin II AT(2) receptor agonists with reduced CYP 450 inhibition.

Structural alterations to the benzylic position of the first drug-like selective angiotensin II AT(2) receptor agonist (1) have been performed, with the emphasis to reduce the CYP 450 inhibitory property of the initial structure. The imidazole moiety, responsible for the CYP 450 inhibitory effect in 1, was replaced with various heterocycles. In addition, the modes of attachment of the heterocycles, that is, carbon versus nitrogen attachment, and introduction of carbonyl functionalities to the benzylic position have been evaluated.

Novel findings of Langerhans cells and interleukin-17 expression in relation to the acrosyringium and pustule in palmoplantar pustulosis.

Background: Palmoplantar pustulosis (PPP) is a chronic and intensely inflammatory skin disease with pustules, erythema and scaling localized to the palms and soles. To date, no specific treatment is known. Earlier findings indicate the acrosyringium as the target for the inflammation.

Interaction between early maternal smoking and variants in TNF and GSTP1 in childhood wheezing.

Background: Children exposed to tobacco smoke early in life have a higher risk of wheeze. Individual susceptibility may depend on genetic factors.

Objective: We studied whether variations in single nucleotide polymorphisms (SNPs) in the TNF, glutathione S transferase P1 (GSTP1) and beta2-adrenoreceptor (ADRB2) genes modify the effect of early maternal smoking on the development of childhood asthma, wheeze and allergic sensitization.

Discovery of dipeptides with high affinity to the specific binding site for substance P1-7.

Substance P 1-7 (SP(1-7), H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH) is the major bioactive metabolite of substance P. The interest in this heptapeptide originates from the observation that it modulates, and in certain cases opposes the effects of the parent peptide, e.g.

Late effects of early growth hormone treatment in Down syndrome.

Objective: Down syndrome (DS) is associated with short stature and psychomotor delay. We have previously shown that growth hormone (GH) treatment during infancy and childhood normalizes growth velocity and improves fine motor skill performance in DS. The aim of this study was to investigate late effects of early GH treatment on growth and psychomotor development in the DS subjects from the previous trial.

Optimizing the power of genome-wide association studies by using publicly available reference samples to expand the control group.

Genome-wide association (GWA) studies have proved extremely successful in identifying novel genetic loci contributing effects to complex human diseases. In doing so, they have highlighted the fact that many potential loci of modest effect remain undetected, partly due to the need for samples consisting of many thousands of individuals. Large-scale international initiatives, such as the Wellcome Trust Case Control Consortium, the Genetic Association Information Network, and the database of genetic and phenotypic information, aim to facilitate discovery of modest-effect genes by making genome-wide data publicly available, allowing information to be combined for the purpose of pooled analysis.

Genome-wide association study identifies five loci associated with lung function.

Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883).

The role of the somatotrophic axis in neuroprotection and neuroregeneration of the addictive brain.

Early studies have shown that the abuse of alcohol, central stimulants, and opiates such as heroin destroys brain cells, reducing attention span and memory. However, new research has suggested that there may be a way to regain some of the lost attention and recall. It has recently been shown that brain cells targeted for early death by continued opiate use can be salvaged by injections of synthetic human growth hormone (GH).

Substance P(1-7) induces antihyperalgesia in diabetic mice through a mechanism involving the naloxone-sensitive sigma receptors.

We have recently explored the role of the tachykinin substance P neuroactive fragment substance P(1-7) in the mediation of anti-inflammatory effects using a blister model in the rat paw (Wiktelius et al., 2006). We observed that this heptapeptide induced a dose-dependent inhibitory effect on the substance P-induced response, which was reversible by the non-selective opioid receptor antagonist naloxone.

No increased occurrence of ischemic heart disease prior to the onset of rheumatoid arthritis: results from two Swedish population-based rheumatoid arthritis cohorts.

Objective: To investigate the relative importance of shared etiologies for rheumatoid arthritis (RA) and ischemic heart disease (IHD) in terms of the well-known increased risk of IHD in patients with RA, by assessing the occurrence of IHD up until the time of the onset of the first symptoms of RA.

Methods: We assessed the prevalence of a history of IHD, myocardial infarction (MI), and angina pectoris before the onset of RA symptoms in 2 large population-based case-control studies. Patients with newly diagnosed RA according to the criteria of the American College of Rheumatology were included as cases.

Nandrolone decanoate administration elevates hippocampal prodynorphin mRNA expression and impairs Morris water maze performance in male rats.

The misuse of anabolic androgenic steroids has in several reports been associated with effects resulting in altered behavior. This study used the Morris water maze task to investigate the effect of high doses of the anabolic androgenic steroid nandrolone on spatial learning and memory in male rats. During the experiment, we observed a significantly impaired Morris water maze performance in the nandrolone-treated rats compared with controls.

Modification of the interleukin-6 response to air pollution by interleukin-6 and fibrinogen polymorphisms.

Background: Evidence suggests that cardiovascular effects of air pollution are mediated by inflammation and that air pollution can induce genetic expression of the interleukin-6 gene (IL6).

Objectives: We investigated whether IL6 and fibrinogen gene variants can affect plasma IL-6 responses to air pollution in patients with cardiovascular disease.

Methods: We repeatedly determined plasma IL-6 in 955 myocardial infarction survivors from six European cities (n = 5,539).

Associations of long- and short-term air pollution exposure with markers of inflammation and coagulation in a population sample.

Background: Exposure to elevated levels of ambient air pollutants can lead to adverse cardiovascular effects. Potential mechanisms include systemic inflammation and perturbation of the coagulation balance.

Objectives: To investigate long- and short-term effects of air pollution exposure on serum levels of inflammatory (IL-6, TNF-alpha and CRP) and coagulation (fibrinogen and PAI-1) markers relevant for cardiovascular pathology.