A controlled study on the preventive effect of ketotifen, an antiallergic agent, on methacholine-induced bronchoconstriction in asthmatics.

We studied the preventive effect of ketotifen, an oral drug with antianaphylactic and antihistaminic properties on methacholine-induced bronchoconstriction in controlled cross-over experiments in twenty-six adult patients with extrinsic asthma. Both a single dose of 1 mg ketotifen and 4 weeks treatment of ketotifen, 1 mg twice daily, failed to reduce the methacholine-induced drop in peak expiratory flow. The spirometric findings remained unchanged during ketotifen treatment. There was no difference between treatments with ketotifen and placebo with regard to the patients assessment of the severity of asthma or airway sensitivity to tobacco smoke, fumes or dusts, or exercise. The results suggest that treatment during 4 weeks with ketotifen does not reduce unspecific broncial hyperreactivity in patients with extrinsic asthma.     

Indoleamine 2,3-dioxygenase activation and depressive symptoms: results from the young Finns study

Objective To examine whether the activation of indoleamine 2,3-dioxygenase (IDO), an enzyme involved in serotonin production, is associated with depressive symptoms. Methods The participants were 544 women and 442 men (aged 24-39 years) from the population-based Young Finns Study who participated in a medical examination in 2001 (including IDO and depression) and 2007 (follow-up assessment for depression). Results At baseline, IDO was associated with depressive symptoms (in the total cohort: B = 0.23, p < .001; women: B = 0.20, p = .007; men: B = 0.29, p = .002; p for interaction = .19). IDO at baseline was also associated with depressive symptoms at follow-up in women (B = 0.17, p = .03), which remained significant when adjusting for any of the biologic and behavioral risk factors. Adjusting for body mass index attenuated the association by 6%. In the final model including all baseline variables, none of the risk factors (except for baseline depressive symptoms) were associated with depressive symptoms at follow-up. Conclusions These data suggest that IDO activity may be a risk factor for future depression especially in women. IDO-induced alterations in serotonergic function may offer one biologic explanation to the well-established associations between inflammation and depression.     

Apolipoprotein E genotype is related to plasma levels of C-reactive protein and lipids and to longevity in nonagenarians

OBJECTIVE: Apolipoprotein E (APOE) genotype is a regulator of hepatic lipoprotein metabolisms and has been linked with longevity. The relationship between APOE genotype and plasma C-reactive protein (CRP), which is produced by the liver during inflammation, has not been studied in nonagenarians. The aim of the present study was to establish whether APOE genotype is related to plasma concentrations of CRP and lipids, or longevity among nonagenarians. DESIGN AND PATIENTS: This cross-sectional study consisted of 291 Finnish nonagenarians and three previously described and genotyped control populations from the same area (i.e. newborns, 40-year-olds, and 70-year-olds). RESULTS: In all nonagenarians and especially in women (P= 0.038), CRP level decreased linearly in the genotype order of epsilon2/2, epsilon2/3, epsilon3/3, epsilon2/4, epsilon3/4 and epsilon4/4. Total (P= 0.009) and low-density lipoprotein (LDL) cholesterol (P = 0.076) levels, in turn, were increased in the epsilon4 allele carriers. In newborns, the epsilon4 frequency was 0.192, in 40-year-olds 0.181, in 70-year-olds 0.179 and in nonagenarians 0.095 (P < 0.0001). The decrease in the epsilon4 allele frequency in the elderly was more clearly seen in women than in men. CONCLUSIONS: APOEepsilon4 allele seems to be associated with decreased inflammatory response as measured by CRP among nonagenarians. This finding may partly explain why some epsilon4 allele carriers can reach very old age despite increased risk of hypercholesterolaemia.     

How the harm reduction movement contrasts itself against punitive prohibition

On the basis of the harm reduction movement's founding texts from the beginning of the 1990s, this paper reflects the movement's self-understanding in contrasting itself with the system of punitive prohibition. Following this is a discussion of the implications for drug users of harm reduction claims-making. The paper concludes that the principles of the harm reduction movement resonate extremely well with the moral sensibilities of our contemporary societies, and but that the movement's claims for an amoral, rational, just, and emancipating approach to drug use are to be seen rather as a powerful rhetorical intervention in the highly moralised landscape of drug debate than something that would be achieved in practice.     

Complement factor H 402His variant confers an increased mortality risk in Finnish nonagenarians: The Vitality 90+ study

Ageing is characterized by chronic low-grade inflammation and the expected lifespan may be affected by several immunological and inflammatory mediators. In this study, we investigated whether the functional Tyr402His polymorphism (rs1061170) on complement factor H (CFH) gene, which is a key inflammatory downregulator, modulates the longevity of 491 nonagenarians in the Vitality 90+ study. Logistic regression analysis and Kaplan–Meier method with the log rank test were used to examine the effect of the CFH Tyr402His polymorphism on 4-year mortality. After follow-up, we observed that risk factor-adjusted mortality was significantly higher among the carriers of CFH 402His allele compared to non-carriers (OR 1.78, 95% CI 1.19–2.67, p = 0.005) and that the survival curves of CFH 402His carriers and non-carriers deviated significantly (p = 0.016). We propose that the increased mortality is inflammation-related and mediated by aberrant complement regulation by the CFH 402His variant.     

Association between the C957T polymorphism of the dopamine D2 receptor gene and schizophrenia

The aim of this study was to investigate the relationship between the functional C957T single-nucleotide polymorphism of the dopamine D2 receptor (DRD2) gene and the risk for schizophrenia. We therefore conducted a case-control association study of 188 Finnish schizophrenia patients meeting the DSM-IV criteria and 384 healthy controls. The 5' nuclease assay (TaqMan) was used to determine genotypes. A greater proportion of patients with schizophrenia than healthy controls were C-allele carriers (odds ratio 1.5, 95% confidence interval (CI) 1.0-2.3, P=0.05). Our results are in agreement with an earlier association study suggesting that the C957T C-allele plays a role in the genetic vulnerability for schizophrenia and support the involvement of the DRD2 gene in schizophrenia pathogenesis.     

Toll-like receptor 4 polymorphism is associated with coronary stenosis but not with the occurrence of acute or old myocardial infarctions

OBJECTIVE: Atherosclerosis is considered to be a chronic inflammatory disease. Toll-like receptor 4 (TLR-4), a key mediator in activating inflammatory cascade, has an A-to-G functional polymorphism that changes aspartic acid to glycine at position 299. TLR-4 is activated by, for example, lipopolysaccharides. The purpose of this study was to investigate the role of a common Asp299Gly polymorphism of the TLR-4 gene in atherosclerosis. MATERIAL AND METHODS: The study comprised autopsy material from 657 men (the Helsinki Sudden Death Study; mean age 53, range 33-70 years). RESULTS: Fewer G-allele carriers had 3-vessel coronary artery disease compared with AA homozygotes (OR 0.32; 95 % CI, 0.12-0.88, p = 0.027), and they also had a lower mean value for maximal coronary stenosis (p = 0.019). TLR-4 polymorphism was not significantly associated with the occurrence of acute or old myocardial infarction (MI). CONCLUSIONS: The G allele of the TLR-4 gene, which is associated with a lower inflammation response, was associated with a lower risk of coronary stenosis but not with the occurrence of MI and hence is not a major factor in the development of coronary atherosclerosis.     

RGS4 polymorphism and response to electroconvulsive therapy in major depressive disorder

We studied the association between RGS4 (rs951436) polymorphism and treatment response in electroconvulsive therapy (ECT) as well as risk of treatment-resistant depression. The study sample consisted of 119 patients with major depressive disorder (MDD) and 384 healthy control subjects. RGS4 polymorphism was not associated with treatment response in ECT or risk of MDD. According to the present data, the impact of RGS4 genotype is not decisive in major depressive disorder. The results provide preliminary data on the impact of RGS4 polymorphism in treatment response in ECT.