Spontaneous 24-h ghrelin secretion pattern in fasting subjects: maintenance of a meal-related pattern.

OBJECTIVE: Ghrelin stimulates GH release and causes weight gain through increased food intake and reduced fat utilization. Ghrelin levels were shown to rise in the preprandial period and decrease shortly after meal consumption, suggesting a role as a possible meal initiator. However, ghrelin secretion in fasting subjects has not yet been studied in detail. DESIGN: 24-h ghrelin profiles were studied in six healthy volunteers (three females; 25.5 years; body mass index 22.8 kg/m(2)) and compared with GH, insulin and glucose levels. METHODS: Blood samples were taken every 20 min during a 24-h fasting period and total ghrelin levels were measured by RIA using a polyclonal rabbit antibody. The circadian pattern of ghrelin secretion and pulsatility (Cluster analysis) were evaluated. RESULTS: An increase and spontaneous decrease in ghrelin were seen at the timepoints of customary meals. Ghrelin was secreted in a pulsatile manner with approximately 8 peaks/24 h. An overall decrease in ghrelin levels was observed during the study period. There was no correlation of ghrelin with GH, insulin or blood glucose levels. CONCLUSIONS: This pilot study indicates that fasting ghrelin profiles display a circadian pattern similar to that described in people eating three times per day. In a fasting condition, GH, insulin and glucose do not appear to be involved in ghrelin regulation. In addition, we found that ghrelin is secreted in a pulsatile pattern. The variation in ghrelin independently of meals in fasting subjects supports previous observations that it is the brain that is primarily involved in the regulation of meal initiation.

Effect of intestinal microfloras from vegetarians and meat eaters on the genotoxicity of 2-amino-3-methylimidazo[4,5-f]quinoline, a carcinogenic heterocyclic amine.

Aim of this study was to investigate the impact of intestinal microfloras from vegetarians and non-vegetarians on the DNA-damaging activity of 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), a carcinogenic heterocyclic amine that is found in fried meats. Floras from four vegetarians (Seventh Day Adventists) and from four individuals who consumed high amounts of meats were collected and inoculated into germfree F344 rats. The rats were kept on isocaloric diets that either contained animal derived protein and fat (meat consumers group) or proteins and fat of plant origin (vegetarian groups). IQ (90 mg/kg bw) was administered orally, after 4 h the extent of DNA-damage in colon and liver cells was determined in single cell gel electrophoresis assays. In all groups, the IQ induced DNA-migration was in the liver substantially higher than in the colon. In animals harbouring floras of vegetarians, the extent of damage was in both organs significantly (69.2% in the liver, P<0.016 and 64.7%, P<0.042 in the colon, respectively) lower than in the meat consumer groups. Our findings show that diet related differences in the microfloras have a strong impact on the genotoxic effects of IQ and suggest that heterocyclic amines are less genotoxic and carcinogenic in individuals that consume mainly plant derived foods.

Association of microsomal epoxide hydrolase polymorphisms and lung cancer risk.

Microsomal epoxide hydrolase (mEH) plays a dual role in the detoxification and activation of tobacco procarcinogens. Two polymorphisms affecting enzyme activity have been described in the exons 3 and 4 of the mEH gene, which result in the substitution of amino acids histidine to tyrosine at residue 113, and arginine to histidine at residue 139, respectively. We performed a hospital-based case-control study consisting of 277 newly diagnosed lung cancer patients and 496 control subjects to investigate a possible association between these two polymorphisms and lung cancer risk. The polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism and TaqMan assay using DNA from peripheral white blood cells. Logistic regression was performed to calculate odds ratios (ORs), confidence limits (CL) and to control for possible confounders. The exon 3 polymorphism of the mEH gene was associated with a significantly decreased risk of lung cancer. The adjusted OR, calculated relative to subjects with the Tyr113/Tyr113 wild type, for the His113/His113 genotype was 0.38 (95% CL 0.20-0.75). An analysis according to histological subtypes revealed a statistically significant association for adenocarcinomas; the adjusted OR for the His113/His113 genotype was 0.40 (95% CL 0.17-0.94). In contrast, no relationship between the exon 4 polymorphism and lung cancer risk was found. The adjusted OR, calculated relative to the His139/His139 wild type, was for the Arg139/Arg139 genotype 1.83 (0.76-4.44). Our results support the hypothesis that genetically reduced mEH activity may be protective against lung cancer.

A cohort mortality and nested case-control study of French and Austrian talc workers.

OBJECTIVES: To study whether the mortality from non-malignant and malignant respiratory diseases of workers employed in French and Austrian talc mines and mills is related to their long term occupational exposure. METHODS: Two historical cohorts were set up comprising all male subjects who had been working continuously for at least 1 year in a series of talc producing companies in France and Austria. The French cohort consisted of those employed at a site in the French Pyrenees and working between 1 January 1945 and 31 December 1994. The Austrian cohort consisted of the workers employed between 1 January 1972 and 31 December 1995 in one of four industrial sites in the Austrian Alps. The mortality within the cohorts was compared with local death rates. Two nested case-control studies focusing on non-malignant and malignant respiratory diseases were set up to estimate possible dose-response relations with cumulative exposure to talc dust based on an industry specific job exposure matrix. RESULTS: Mortality from lung cancer was in small excess in both cohorts (France, standardised mortality ratio (SMR) 1.23, 21 cases observed, 95% confidence interval (95% CI) 0.76 to 1.89; Austria, SMR 1.06, seven observed, 95% CI 0.43 to 2.19). A non-significant excess mortality was found for all non-malignant respiratory diseases in the French cohort due to a significant excess for pneumoconiosis (SMR 5.56, three observed, 95% CI 1.12 to 16.2). The case-control study of non-malignant respiratory disease showed an increased mortality in the highest exposure groups (odds ratio (OR) 2.5 for a cumulative exposure > or = 800 y.mg/m(3)) with a significant trend (OR/100 y.mg/m(3) 1.08) with cumulative exposure to talc. On the contrary, no increasing trend could be found in the case-control study of lung cancer. This result must be interpreted considering the small cohort size. Adjustment on smoking and exposure to quartz did not influence these results to any extent. CONCLUSIONS: The mortality from non-malignant respiratory disease was found to be related to high cumulative exposure to talc dust. The small excess in lung cancer does not seem to be attributable to talc.

Cellular reaction on the anterior surface of 4 types of intraocular lenses.

PURPOSE: To assess the cellular reaction on the anterior surface of 4 types of foldable intraocular lenses (IOLs). SETTING: Department of Ophthalmology, University Hospital of Vienna, Vienna, Austria. METHODS: One hundred eyes scheduled for cataract surgery were prospectively randomized into 4 groups of 25 eyes each using random number tables. Group 1 received a Hydroview IOL (Bausch & Lomb), Group 2 an AcrySof IOL (Alcon), Group 3 a MemoryLens IOL (ORC), and Group 4 a CeeOn 920 IOL (Pharmacia). Patients were examined 1, 3, 7, 30, 90, and 180 days postoperatively. Postoperative biomicroscopic examinations were done with a slitlamp, and a specular microscope was used to document the presence of cell deposits and identify areas with the highest density of cells. RESULTS: The local tissue response revealed 2 patterns: a nonspecific foreign-body reaction to the IOL (small round, fibroblast-like, epithelioid, and giant cells) and a lens epithelial cell (LEC) reaction. The highest incidence of LECs was in the Hydroview group, in which LECs were present on 81.8% of lenses 180 days postoperatively. During the first postoperative days, small round and fibroblast-like cells were found on all IOLs. From 7 days on, the incidence and density of these cells were less severe in the Hydroview and CeeOn 920 groups. After several weeks, epithelioid cells and foreign-body giant cells were seen on some IOLs. These cells appeared more often on AcrySof, MemoryLens, and CeeOn IOLs. CONCLUSION: This study found IOL-related differences in cellular reaction after cataract surgery. The incidence of a nonspecific foreign-body reaction to 4 IOLs is consistent with the results of previous studies. The incidence of LECs was highest in the Hydroview group and lowest in the AcrySof group. The CeeOn 920 group had the lowest incidence of all types of cells.

Symptoms suggestive of atopic rhinitis in children aged 6-9 years and the indoor environment.

BACKGROUND: We aimed to investigate the influence of indoor factors on the prevalence of symptoms suggestive of atopic rhinitis in children aged 6-9 years in Upper Austria. METHODS: We analyzed the results from an extended ISAAC (International Study of Asthma and Allergies in Childhood) questionnaire, answered by the parents, about indoor environment and symptoms strongly suggesting atopic rhinitis. This was defined as having reported a running, obstructed, or itchy nose apart from having a cold in the last year. The overall response rate was 93.4%. After excluding 6,016 children (17.1%) with changed indoor environment (due to allergies in the family), we analyzed the remaining subsample of 18,606 questionnaires. RESULTS: The following factors were associated with an increased risk: mother's smoking during pregnancy and/or during time of breast-feeding (OR 1.28; CI 1.07-1.52), synthetic bedding (OR 1.21; CI 1.09-1.36), dampness/mold at home (OR 1.51; CI 1.31-1.74), central heating with gas (OR 1.75; CI 1.06-2.87), and space heating (OR 1.66; CI 1.01-2.98). Cooking with wood (OR 0.62; CI 0.46-0.84) was negatively associated with symptoms. CONCLUSIONS: The indoor environment plays a role in the symptoms of atopic rhinitis in children. However, the population-attributable risks were not particularly high; they were between -2.7% and 9% for the various exposures considered in this study.

[Prevalence of smoking habits of Upper Austria students of the 7th and 8th grade and effect of smoking habits of family and peers]. / Prävalenz der Rauchgewohnheiten von oberösterreichischen Schülern der 7. und 8. Schulstufe und Einfluss der Rauchgewohnheiten von Familie und Peers.

The aim of the study was to explore the prevalence of different smoking habits in a population of Austrian pupils, 12 to 15 years old, and the relationship of familial and peer group smoking customs with these habits. In 1997 a population-based survey (International Study of Asthma and Allergies in Childhood, ISAAC) was conducted of all 7th and 8th grade school children of a district of Upper Austria. Information on the smoking habits of the adolescents, the family members, and of the peer as well as smoking habits of the teacher, gender, and age of the children was collected. The overall-prevalence of having ever smoked in this population is 57.8%. The percentage of eversmokers among the 12-year-olds is 50%. This amount increases to 63.8% among the 14- to 15-year-olds. The odds ratios for smoking daily is highest among those whose best friend smokes (OR: 70.63, CI: 9.19, 542.40). The risk of daily smoking increases also if the siblings of the juvenile (OR: 4.71, CI: 1.15, 19.35) or the mother (OR: 4.95, CI: 1.67, 14.70) smoke. If the father smokes the risk to smoke monthly is increased (OR: 2.09, CI: 1.28, 3.40). These results point to the fact that smoking prevention programes should take into account the influence of peers and family of the adolescents.

Indoor factors and their association to respiratory symptoms suggestive of asthma in Austrian children aged 6-9 years.

The ISAAC (International Study of Asthma and Allergy in Childhood) was founded in 1990 in order to maximise the value of epidemiological research into asthma and allergic diseases, to describe the prevalence of asthma and allergic disease in children living in different locations, to make comparisons within and between countries, to provide a framework for further etiological research and to find prevention strategies. We analysed a sub-sample of a population-based study (1995 to 1997) in Upper Austria. The aim of our study was to investigate the influence of indoor risk factors on wheezing in children 6-9 years old. Our calculations were based on the results of a questionnaire answered by parents about their children's indoor environment at home. Smoking of the mother during pregnancy and/or during breastfeeding (OR 1.28; 95% CI 1.08-1.48), smoking of the mother at the present time (OR 1.25; 95% CI 1.12-1.41), a bird (OR 1.40; 95% CI 1.06-1.85) or rabbit (OR 1.37; 95% CI 1.03-1.82) as a domestic pet, synthetic bedding (OR 1.33; 95% CI 1.18-1.49) and dampness or mould at home (OR 1.43; 95% CI 1.24-1.65) are associated with a significantly increased risk of childhood wheezing in the last 12 months. Other variables such as "smoking of the father", "cooking with gas", "gas central heating" and other "pets" do not achieve statistical significance.

Additive benefit of PGI2 and PGE1 (via different mechanisms?) on inhibition of activation of human vascular smooth muscle cells?

It seems likely that the antiplatelet action of antiaggregatory prostaglandins (PGE1, PGI2) is not the pivotal mechanism of action involved in clinical improvement of peripheral vascular disease. Based upon earlier results that both of these agents may have a certain effect on proliferation of vascular smooth muscle cells, we approached that question of an "optimal therapeutic regimen" going one step further. Patients having to undergo amputation were given a randomized "last choice" therapy with either PGI2 (once or twice a day, 6 h, 5 ng/kg/min i.v.), PGE1 (once or twice a day, 1 ng/kg/min i.a.) or a combination of both with a 6 h interval in between for 5 consecutive days. The ones who underwent surgery had a pathomorphological examination of vascular segments removed during amputation. The counting of activated smooth muscle cells indicates a significant drop induced by both of the PG's alone. A second infusion a day with the same compound, however, did not induce a further decrease in the activation state. In contrast administering the complimentary PG caused a comparable, significant decrease (p less than 0.01) in activation of smooth muscle cells in the intima and the media as well. It thus seems, that different mechanisms may be involved inducing additive therapeutic benefit. PGI2 is hypothesised to act predominantly by blocking PDGF-release and interference with PDGF, whereas PGE1 may have a more direct vascular action. From these findings, as well as the beneficial clinical results to be reported elsewhere, a combined therapy by the infusion scheme used may be the optimal one for a PG-therapy at the moment, based upon platelet and smooth muscle cell action.

Prostaglandin I2 reduces activation of human arterial smooth muscle cells in-vivo.

Patients suffering from peripheral vascular disease have been "ultima ratio"-treated with PGI2 at a rate of 5 ng/kg/min for 6 hours a day and 5 consecutive days i.v. 20 of them underwent surgery thereafter as therapy was not sufficient. A histological examination and quantification of vascular tissue revealed that the number of activated smooth muscle cells was significantly lower in treated patients vascular segments than in untreated ones in all the different age groups. A comparable suppression was found in the intima and the media as well. It is thus concluded, that PGI2 inhibits smooth muscle cell proliferation most probably by inhibiting PDGF-release from the platelets and stimulation of smooth muscle cell cAMP. To achieve a more beneficial PGI2-effect at the vascular level, a prolonged PGI2-therapy looks rather promising.