| 1. |
- Smits, KM, et al.
(author)
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Association of metabolic gene polymorphisms with tobacco consumption in healthy controls
- 2004
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 110:2, s. 266-270
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Journal article (peer-reviewed)abstract
- Polymorphisms in genes that encode for metabolic enzymes have been associated with variations in enzyme activity between individuals. Such variations could be associated with differences in individual exposure to carcinogens that are metabolized by these genes. In this study, we examine the association between polymorphisms in several metabolic genes and the consumption of tobacco in a large sample of healthy individuals. The database of the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens was used. All the individuals who were controls from the case-control studies included in the data set with information on smoking habits and on genetic polymorphisms were selected (n = 20,938). Sufficient information was available on the following genes that are involved in the metabolism of tobacco smoke constituents: CYPIAI, GSTMI, GSTTI, NAT2 and GSTPI. None of the tested genes was clearly associated with smoking behavior. Information on smoking dose, available for a subset of subjects, showed no effect of metabolic gene polymorphisms on the amount of smoking. No association between polymorphisms in the genes studied and tobacco consumption was observed; therefore, no effect of these genes on smoking behavior should be expected.
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| 3. |
- Ahlström-Emanuelsson, Cecilia, et al.
(author)
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Establishing a model of seasonal allergic rhinitis and demonstrating dose-response to a topical glucocorticosteroid
- 2002
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In: Annals of Allergy, Asthma & Immunology. - 1081-1206. ; 89:2, s. 159-165
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Journal article (peer-reviewed)abstract
- Background: Symptoms of seasonal allergic rhinitis may vary greatly. Hence, for research purposes, there is a need for disease-like models of allergic rhinitis. In a preliminary study, involving 7 days' challenge with allergen, promising symptom consistency was obtained and dose-response to a glucocorticosteroid could, in part, be demonstrated. Objective: To establish this model of seasonal allergic rhinitis and test the hypothesis that mometasone furoate is more potent than budesonide as an antirhinitis drug. Methods: Thirty-eight patients with seasonal allergic rhinitis received treatment with spray-formulations of placebo, budesonide 64 kg, budesonide 256 mug, and mometasone furoate 200 mug in a double-blind, crossover design. After 3 days' treatment, individualized nasal allergen-challenges were administered daily for 7 days while the treatment continued. Nasal symptoms and peak inspiratory flow (PIF) were recorded. Results: During the last 3 days of allergen challenge without active treatment, consistent around-the-clock symptoms were recorded and recordings during these days were used in the analysis. With few exceptions the active treatments reduced nasal symptoms and improved nasal PIF (P values <0.001 to 0.05). Budesonide caused dose-dependent improvements in evening symptoms, morning nasal PIF, and nasal PIF recorded 10 minutes after allergen-challenge (P values <0.05). Budesonide 256 mug produced greater improvement than mometasone furoate 200 mug for nasal PIF 10 minutes after allergen-challenge (P < 0.05). Conclusion: The present allergen challenge method, producing consistent symptoms and nasal PIF data, emerges as a model of seasonal allergic rhinitis well suited for exploring potency and efficacy of drug intervention. The present data do not support the view that mometasone furoate is a more potent antirhinitis drug than budesonide.
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| 4. |
- Astrand, Annika, et al.
(author)
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Mice lacking melanin-concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity.
- 2004
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In: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 287:4, s. R749-58
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Journal article (peer-reviewed)abstract
- Melanin-concentrating hormone (MCH) plays an important role in energy balance. The current studies were carried out on a new line of mice lacking the rodent MCH receptor (MCHR1(-/-) mice). These mice confirmed the previously reported lean phenotype characterized by increased energy expenditure and modestly increased caloric intake. Because MCH is expressed in the lateral hypothalamic area, which also has an important role in the regulation of the autonomic nervous system, heart rate and blood pressure were measured by a telemetric method to investigate whether the increased energy expenditure in these mice might be due to altered autonomic nervous system activity. Male MCHR1(-/-) mice demonstrated a significantly increased heart rate [24-h period: wild type 495 +/- 4 vs. MCHR1(-/-) 561 +/- 8 beats/min (P < 0.001); dark phase: wild type 506 +/- 8 vs. MCHR1(-/-) 582 +/- 9 beats/min (P < 0.001); light phase: wild type 484 +/- 13 vs. MCHR1(-/-) 539 +/- 9 beats/min (P < 0.005)] with no significant difference in mean arterial pressure [wild type 110 +/- 0.3 vs. MCHR1(-/-) 113 +/- 0.4 mmHg (P > 0.05)]. Locomotor activity and core body temperature were higher in the MCHR1(-/-) mice during the dark phase only and thus temporally dissociated from heart rate differences. On fasting, wild-type animals rapidly downregulated body temperature and heart rate. MCHR1(-/-) mice displayed a distinct delay in the onset of this downregulation. To investigate the mechanism underlying these differences, autonomic blockade experiments were carried out. Administration of the adrenergic antagonist metoprolol completely reversed the tachycardia seen in MCHR1(-/-) mice, suggesting an increased sympathetic tone.
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| 5. |
- Canova, C R, et al.
(author)
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Increased prevalence of perennial allergic rhinitis in patients with obstructive sleep apnea
- 2004
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In: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 71:2, s. 138-143
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Journal article (peer-reviewed)abstract
- Background: Impaired nasal breathing is a risk factor for obstructive sleep apnea syndrome (OSAS). Objectives: The aim of this study was to determine whether atopy to perennial allergens and existence of perennial allergic rhinitis was a risk factor for OSAS. Methods: In a case-control study, we compared the proportions of OSAS patients with atopy to perennial allergens and perennial allergic rhinitis to the proportions in patients with chronic obstructive pulmonary disease (COPD). Seventy-two OSAS patients (mean age 60.7 years; 79.4% male) and 44 COPD patients (mean age 63.6 years; 88.6% male) were selected from a hospital outpatients' clinic in Switzerland. All patients completed a respiratory symptom questionnaire, performed spirometry and had a skin prick test for atopy. Results: OSAS patients were significantly heavier than COPD patients (BMI 32.4 +/- (SD) 6.6 vs. 29.2 +/- 6.6 kg/m(2), p = 0.04) and had a better lung function than COPD patients (FEV1% predicted 91.3 +/- 19.2 vs. 51.6 +/- 18.9%, p < 0.001). Patients with OSAS were more likely to be sensitized to perennial allergens such as house dust mite (23.6 vs. 4.5%, p = 0.009) and dog (18 vs. 4.5%, p = 0.04) than the COPD patients. Perennial allergic rhinitis ( having nose problems [ nasal obstruction and/or runny nose and/or sneezing] all year and being atopic to at least one perennial allergen) was reported in 11% of OSAS patients but in only 2.3% of COPD patients (p = 0.15). Conclusion: We conclude that subjects with OSAS may have an increased risk of being allergic to perennial allergens and suffer from perennial rhinitis. Awareness of this risk may have important consideration in the clinical situation.
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| 6. |
- Downie, SR, et al.
(author)
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Association between nasal and bronchial symptoms in subjects with persistent allergic rhinitis
- 2004
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In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 59:3, s. 320-326
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Journal article (peer-reviewed)abstract
- Background: The association between nasal and bronchial symptoms, and the course of bronchial responsiveness and airway inflammation in house dust mite sensitive persistent rhinitis over a prolonged time period has not been thoroughly explored. Objective: To determine if nasal symptoms were associated with bronchial symptoms in persistent rhinitic subjects, and to assess their bronchial responsiveness and airway inflammation in comparison to nonrhinitic, nonatopic controls. The additional impact of pollen sensitivity on the lower airways in rhinitic subjects was also addressed. Methods: Rhinitics and controls answered telephone symptom questionnaires once every 2 weeks for 1 year. Every 3 months, exhaled nitric oxide (eNO) and bronchial responsiveness to histamine were measured. Results: Thirty-seven rhinitics and 19 controls completed the study. High nasal symptom scores in rhinitic subjects were associated with bronchial symptoms (OR = 1.7, 95% CI 1.2-2.5). Bronchial hyper-responsiveness was present in 32.4% of rhinitic subjects on at least one clinical visit during the year. Pollen allergy caused seasonal variation in eNO (P = 0.03). Conclusion: In persistent rhinitic subjects, high nasal symptom scores were associated with bronchial symptoms, and many subjects experienced bronchial hyper-responsiveness during the year. Persistent rhinitic subjects were more at risk than healthy adults of bronchial symptoms and airway inflammation, which are likely risk factors for asthma.
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| 9. |
- Garey, J, et al.
(author)
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Genetic contributions to generalized arousal of brain and behavior
- 2003
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 100:19, s. 11019-11022
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Journal article (peer-reviewed)abstract
- We have identified a generalized arousal component in the behavior of mice. Analyzed by mathematical/statistical approaches across experiments, investigators, and mouse populations, it accounts for about 1/3 of the variance in arousal-related measures. Knockout of the gene coding for the classical estrogen receptor (ER-α), a ligand-activated transcription factor, greatly reduced arousal responses. In contrast, disrupting the gene for a likely gene duplication product, ER-β, did not have these effects. A combination of mathematical and genetic approaches to arousal in an experimentally tractable mammal opens up analysis of a CNS function of considerable theoretical and practical significance.
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| 10. |
- Garner, J., et al.
(author)
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Identification of Aminopyrimidine Regioisomers via Line Broadening Effects in 1H and 13C NMR Spectroscopy
- 2004
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In: Australian Journal of Chemistry. ; 57:11, s. 1079-1083
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Journal article (peer-reviewed)abstract
- Substituted mono- and diamino-pyrimidines were synthesized as part of our medicinal chemistry programmes. Primary amines substituted at the 4-position exhibited room-temperature line broadening effects in both 1H and 13C NMR spectroscopy due to the presence of rotamers, but these effects were not observed for substituents in the 2-position. This provided a simple diagnostic tool for the identification of regioisomers, a determination which would otherwise have required two-dimensional experiments.
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