Quantitative trait loci near the insulin-degrading enzyme (IDE) gene contribute to variation in plasma insulin levels

Insulin-degrading enzyme (IDE) plays a principal role in the proteolysis of several peptides in addition to insulin and is encoded by IDE, which resides in a region of chromosome 10q that is linked to type 2 diabetes. Two recent studies presented genetic association data on IDE and type 2 diabetes (one positive and the other negative), but neither explored the fundamental question of whether polymorphism in IDE has a measurable influence on insulin levels in human populations. To address this possibility, 14 single nucleotide polymorphisms (SNPs) from a linkage disequilibrium block encompassing IDE have been genotyped in a sample of 321 impaired glucose tolerant and 403 nondiabetic control subjects. Analyses based on haplotypic genotypes (diplotypes), constructed with SNPs that differentiate common extant haplotypes extending across IDE, provided compelling evidence of association with fasting insulin levels (P = 0.0009), 2-h insulin levels (P = 0.0027), homeostasis model assessment of insulin resistance (P = 0.0001), and BMI (P = 0.0067), with effects exclusively evident in men. The strongest evidence for an effect of a single marker was obtained for rs2251101 (located near the 3' untranslated region of IDE) on 2-h insulin levels (P = 0.000023). Diplotype analyses, however, suggest the presence of multiple interacting trait-modifying sequences in the region. Results indicate that polymorphism in/near IDE contributes to a large proportion of variance in plasma insulin levels and correlated traits, but questions of sex specificity and allelic heterogeneity will need to be taken into consideration as the molecular basis of the observed phenotypic effects unfolds.     

Health promotion activities in annual reports of local governments: 'Health for All' targets as a tool for content analysis

BACKGROUND: This article presents an instrument to study the annual reporting of health promotion activities in local governments within the three intervention municipalities of the Stockholm Diabetes Prevention Program (SDPP). The content of health promotion activities are described and the strengths, weaknesses and relevance of the method to health promotion discussed. METHOD: A content analysis of local governmental reports from 1995-2000 in three Swedish municipalities. A matrix with WHO's 38 'Health for All' (HFA) targets from 1991 was used when coding the local health promotion activities. RESULTS: There are many public health initiatives within the local governmental structure even if they are not always addressed as health promotion. The main focuses in the local governmental reports were environmental issues, unemployment, social care and welfare. CONCLUSIONS: Local governmental reports were found to be a useful source of information that could provide knowledge about the priorities and organizational capacities for health promotion within local authorities. Additionally the HFA targets were an effective tool to identify and categorize systematically local health promotion activities in the annual reports of local governments. Identifying local health promotion initiatives by local authorities may ease the development of a health perspective and joint actions within the existing political and administrative structure. This paper provides a complementary method of attaining and structuring information about the local community for developments in health promotion.     

Selectivity of Bevantolol Hydrochloride,a β-Adrenoceptor Antagonist,in Asthmatic Patients

Bevantolol hydrochloride, a new β-adrenoceptor antagonist, has been shown to be cardioselective in animals. To evaluate its selectivity in humans, a double-blind, crossover study was conducted in 8 asthmatics. Following a single oral dose of placebo, bevantolol 75 or 150 mg or propranolol hydrochloride 40 mg, forced expiratory volume in 1 second (FEV₁), heart rate, blood pressure and skeletal muscle tremor were measured before and after 4 increasing intravenous doses of terbutaline sulfate to establish terbutaline dose-reponse curves. The FEV₁ decreased after all active treatments. During terbutaline infusions there was an increase in FEV₁ after both bevantolol doses and placebo. The terbutaline dose-response curve after bevantolol shifted to the right, however. After propranolol, there was no increase in FEV₁ during terbutaline stimulation. Heart rate and skeletal muscle tremor showed a similar pattern during the experiment. In dosages that have previously been shown to produce at least the same degree of blockade of exercise-induced tachycardia, bevantolol has less influence on terbutaline-induced bronchodilation, heart rate increase and skeletal muscle tremor than did propranolol. Thus bevantolol has relative β₁-adrenoceptor antagonist selectivity. Drawing upon the results of a previous study in the same patients, we believe bevantolol, atenolol and metoprolol have similar β₁-selectivity.     

Analysis of urinary catecholamines: an improved auto-analyzer fluorescence method

An improved automated procedure for analysis of urinary catecholamines, based on the trihydroxyindole reaction is presented. The steps of the analysis and the significance of the reagents are studied systematically. Changes of the catecholamine contents during storage of urines and eluates is investigated. The Chromatographic step is speeded up. Concentrations of chemicals, pH and reaction times are made optimal for maximal sensitivity and best differentiation between adrenaline and noradrenaline. The result is a reliable, sensitive and rapid semi-automated technique for quantitative differential analysis of urinary adrenaline and noradrenaline.The capacity of both steps of the analysis is high. Thus, 40 urines can be chromatographed per day or 90 eluates can be analysed per day by one laboratory technician.The method has a high reproducibility and good specificity. However, high amounts of methyldopa or l-dopa interfere with the analysis. A rapid and simple method is described for detecting the presence of interfering substances in urine from patients given methyldopa or l-dopa.     

Nasal neutrophil activity and mucinous secretory responsiveness in COPD

Patients with chronic obstructive pulmonary disease (COPD) frequently report nasal symptoms. In the present study, we have examined whether or not COPD is associated with any nasal inflammation. Plasma exudation evoked by histamine challenges has been employed to improve the recovery of inflammatory indices in nasal lavage fluids. In 23 COPD-patients and 26 healthy subjects, all without history or signs of allergic rhinitis, nasal polyposis, or chronic rhinosinusitis, nasal saline-lavages were performed with and without histamine. alpha2-Macroglobulin, fucose, eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were determined as indices of plasma exudation, mucinous secretion, eosinophil activity and neutrophil activity, respectively. The difference in MPO-levels between the histamine and the saline lavage was greater in COPD patients compared with healthy subjects (P<0.05). Also, COPD patients reporting nasal symptoms presented an increase in MPO at histamine challenge (P<0.05, cf. saline) and greater differences in MPO and fucose, respectively, between the histamine and the saline lavage (P<0.05, cf. patients without symptoms). We conclude that COPD is not associated with any marked nasal inflammation. However, our observation on increased MPO-levels at histamine challenge suggests some degree of increased neutrophil activity in this condition. Furthermore, when associated with nasal symptoms, COPD may be associated with an increased nasal secretory responsiveness.     

Transportation noise and incidence of hypertension

Background

The evidence on exposure to transportation noise and development of hypertension is inconclusive, mostly because of a lack of high quality studies of longitudinal design.

Stimulated salivary flow rate and buffer effect in schoolchildren from Greenland and Sweden: a comparative study

OBJECTIVE: To compare food habits and stimulated salivary flow rate and buffer effect between schoolchildren from Greenland and Sweden and to evaluate whether the change in lifestyle concerning eating habits in Sweden during recent decades has resulted in any obvious alteration in these salivary properties. MATERIAL AND METHODS: Fifty healthy schoolchildren from Greenland were included and compared with 50 age-matched and gender-matched Swedish children. Whole saliva stimulated by chewing was collected, and prior to sampling each participant filled in a simple questionnaire regarding their food habits. RESULTS: Salivary flow rate and buffer effect were significantly (p<0.001) higher for the Greenlandic children. The difference in flow rate was on average 0.71 ml/min. Milk, fish/meat and fruit/vegetables were more frequently consumed by the Swedish children, while snacks, soft drinks and sweets had a higher consumption frequency on Greenland. No obvious correlation could be found between consumption frequency of the tested food products and flow rate or buffer effect of saliva. Twenty-nine Swedish children were within the age range+/-6 months of an age with earlier documented values of stimulated salivary flow rate. Twenty-six of these 29 Swedish children were within the 25-75 percentile range of the old values, while 22 of their Greenlandic "twins" were in or above percentile 75. CONCLUSIONS: Obvious differences in salivary flow rate and buffer effect between schoolchildren from Greenland and Sweden illustrated the importance of being cautious when exchanging reference data between different cultures/ethnic groups.     

Lactobacillus-mediated interference of mutans streptococci in caries-free vs. caries-active subjects

In order to assess whether naturally occurring oral lactobacilli have probiotic properties, lactobacilli were isolated from saliva and plaque from children and adolescents, with or without caries lesions. The interference capacities of these lactobacilli were investigated against a panel of 13 clinical isolates and reference strains of Streptococcus mutans and Streptococcus sobrinus, as well as against the subject's autologous mutans streptococci, using the agar-overlay technique. Lactobacillus-mediated inhibition differed significantly between the three subject groups (no caries, arrested caries, or active caries), demonstrating increased inhibition in subjects without present or previous caries experience compared to subjects with arrested caries or subjects presenting with frank lesions. Lactobacilli from subjects lacking S. mutans inhibited the growth of the test panel of mutans streptococci significantly better than lactobacilli from subjects who were colonized. Furthermore, subjects without caries experience harbored lactobacilli that more effectively repressed the growth of their autologous mutans streptococci. Twenty-three Lactobacillus spp. completely inhibited the growth of all mutans streptococci tested. Species with maximum interference capacity against mutans streptococci included Lactobacillus paracasei, Lactobacillus plantarum, and Lactobacillus rhamnosus. Naturally occurring oral lactobacilli significantly inhibited the growth of both test strains of mutans streptococci and the subject's autologous mutans streptococci in vitro, and this effect was more pronounced in caries-free subjects.