| 1. |
- Wan, Y., et al.
(författare)
-
First reported nonpeptide AT1 receptor agonist (L-162,313) acts as an AT2 receptor agonist in vivo
- 2004
-
Ingår i: J Med Chem. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 47:6, s. 1536-1546
-
Tidskriftsartikel (refereegranskat)abstract
- In this investigation, it is demonstrated that the first nonpeptide AT(1) receptor agonist L-162,313 (1), disclosed in 1994, also acts as an agonist at the AT(2) receptor. In anesthetized rats, administration of compound 1 intravenously or locally in the duodenum increased duodenal mucosal alkaline secretion, effects that were sensitive to the selective AT(2) receptor antagonist PD-123,319. The data strongly suggest that 1 is an AT(2) receptor agonist in vivo. To the best of our knowledge, this substance is the first nonpeptidic low-molecular weight compound with an agonistic effect mediated through the AT(2) receptor.
|
|
| 2. |
- Ewert, Sara, 1974, et al.
(författare)
-
Dynamic expression of the angiotensin II type 2 receptor and duodenal mucosal alkaline secretion in the Sprague-Dawley rat
- 2006
-
Ingår i: Experimental Physiology. - : Wiley. - 0958-0670. ; 91:1, s. 191-199
-
Tidskriftsartikel (refereegranskat)abstract
- Activation of angiotensin II type 2 receptors (AT2R) has been shown to stimulate duodenal mucosal alkaline secretion (DMAS) in Sprague-Dawley rats (S-D). This finding could not be confirmed in another line of S-D, and the present study investigates whether the level of AT2R expression determines the response to the AT2R agonist CGP42112A. DMAS was measured in anaesthetized rats using in situ pH-stat titration. Real-time PCR and Western blot were used to assess AT1R and AT2R RNA and protein expression, respectively. CGP42112A (0.1 microg kg(-1)min(-1) I.V.) elicited a 45% net increase in DMAS in the previous S-D line studied, whereas no change occurred in the new S-D line. Luminal administration of prostaglandin E2 (10(-5) M) increased DMAS similarly in both S-D lines. AT2R protein expression was significantly higher in tissue from the previous line compared to the new line. Individual AT1R to AT2R ratios (RNA and protein) were significantly higher in the new line compared to the previous S-D line. In the new S-D line intravenous infusion of angiotensin II (Ang II; 10 microg kg(-1) h(-1)) over 120 min significantly lowered the duodenal AT1aR to AT2R RNA ratio. Prolonged Ang II infusion over 240 min increased AT2R protein expression and evoked a 42% stimulatory response in DMAS to CGP42112A. The level of local AT2R expression determines the effect of the AT2R agonist CGP42112A on rat duodenal mucosal alkaline secretion. AT2R expression should be confirmed before interpreting the experimental effects of pharmacological interferences with this receptor.
|
|
| 3. |
- Ewert, Sara, 1974, et al.
(författare)
-
The bradykinin BK2 receptor mediates angiotensin II receptor type 2 stimulated rat duodenal mucosal alkaline secretion.
- 2003
-
Ingår i: BMC physiology. - 1472-6793. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study investigates bradykinin and nitric oxide as potential mediators of AT2-receptor-stimulated duodenal mucosal alkaline secretion. Duodenal mucosal alkaline secretion was measured in methohexital- and alpha-chloralose-anaesthetised rats by means of in situ pH-stat titration. Immunohistochemistry and Western blot were used to identify the BK2 receptors. RESULTS: The AT2 receptor agonist CGP42112A (0.1 microg kg(-1) min(-1)) administered intravenously increased the duodenal mucosal alkaline secretion by approximately 50 %. This increase was sensitive to the selective BK2 receptor blocker HOE140 (100 ng/kg i.v.), but not to luminal administration of the NOS blocker L-NAME (0.3 mM). Mean arterial pressure did not differ between groups during the procedures. Immunohistochemistry showed a distinct staining of the crypt epithelium and a moderate staining of basal cytoplasm in villus enterocytes. CONCLUSION: The results suggest that the AT2-receptor-stimulated alkaline secretion is mediated via BK2 receptors located in the duodenal cryptal mucosal epithelium.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Kirkeleit, Jorunn, et al.
(författare)
-
Early life exposures contributing to accelerated lung function decline in adulthood – a follow-up study of 11,000 adults from the general population
- 2023
-
Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 66
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to assess whether exposure to risk factors in early life from conception to puberty continue to contribute to lung function decline later in life by using a pooled cohort comprising approx. 11,000 adults followed for more than 20 years and with up to three lung function measurements. Methods: Participants (20–68 years) in the ECRHS and NFBC1966 cohort studies followed in the periods 1991–2013 and 1997–2013, respectively, were included. Mean annual decline in maximum forced expired volume in 1 s (FEV1) and forced vital capacity (FVC) were main outcomes. Associations between early life risk factors and change in lung function were estimated using mixed effects linear models adjusted for sex, age, FEV1, FVC and height at baseline, accounting for personal smoking. Findings: Decline in lung function was accelerated in participants with mothers that smoked during pregnancy (FEV1 2.3 ml/year; 95% CI: 0.7, 3.8) (FVC 2.2 ml/year; 0.2, 4.2), with asthmatic mothers (FEV1 2.6 ml/year; 0.9, 4.4) (FEV1/FVC 0.04 per year; 0.04, 0.7) and asthmatic fathers (FVC 2.7 ml/year; 0.5, 5.0), and in women with early menarche (FVC 2.4 ml/year; 0.4, 4.4). Personal smoking of 10 pack-years contributed to a decline of 2.1 ml/year for FEV1 (1.8, 2.4) and 1.7 ml/year for FVC (1.3, 2.1). Severe respiratory infections in early childhood were associated with accelerated decline among ever-smokers. No effect-modification by personal smoking, asthma symptoms, sex or cohort was found. Interpretation: Mothers’ smoking during pregnancy, parental asthma and early menarche may contribute to a decline of FEV1 and FVC later in life comparable to smoking 10 pack-years. Funding: European Union's Horizon 2020; Research Council of Norway; Academy of Finland; University Hospital Oulu; European Regional Development Fund; Spanish Ministry of Science and Innovation; Generalitat de Catalunya.
|
|
| 7. |
- Nordström, Moa, 1982, et al.
(författare)
-
Pseudophakia and Lens Opacities in 70-Year-Olds in Gothenburg, Sweden; Gender Differences, Impact on Self-Reported Visual Function and Validation of Self-Reported Cataract and Pseudophakia
- 2022
-
Ingår i: Clinical Ophthalmology. - 1177-5483. ; 16, s. 3269-3281
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The study aimed at determining the prevalence and sex differences in cataract, pseudophakia, lens opacities and self -reported cataract in 70-year-old people in Gothenburg, Sweden. The purpose was also to identify correlations between lens opacities, visual acuity and subjective visual function, and to validate self-reported cataract and cataract surgery.Patients and Methods: Population-based cross-sectional study where participants (n=1182) answered questions about self-reported diagnosis of cataract and cataract surgery. A total of 1139 subjects completed the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25), 560 subjects underwent ophthalmic examination including visual acuity and lens photography. t-test, Pearson chi-square and Mann-Whitney U-test were used for obtaining p-values. ANOVA (analysis of variances, Kruskal- Wallis, one-way) was used to compare VFQ-25 between 3 groups; no cataract, cataract and pseudophakia. To clarify the differences between specific pairs of groups post-hoc test (Bonferroni) was used after ANOVA.Results: Self-reported cataract was more common in women than in men (27.2% vs 19.1%, p=0.001, chi-square). Cataract surgery was reported by 16.3% of women and 12.6% of men (p=0.072). Upon eye examination, the prevalence of pseudophakia was 16.9% in women compared to 10.2% in men (p=0.020). The prevalence of cataract, including pseudophakia, was 31.9% in women versus 23.8% in men (p=0.033). Significant correlations (Spearman's rho) were found between lens opacities and visual acuity. Self-reported cataract surgery showed a very high specificity and high sensitivity. The composite score from NEI VFQ-25 was lower in people with pseudophakia than in people with/without cataract (p=0.012, Kruskal-Wallis).Conclusion: The prevalence of cataract including pseudophakia in 70-year-olds in Gothenburg is higher compared to previous studies in similar geographical areas. Also, it is more common in women than in men. The lack of significant sex differences in lens opacities may be due to cataract surgery at an earlier stage. Validation showed very good agreement between pseudophakia and self-reported cataract surgery.
|
|
| 8. |
- Rydberg Sterner, Therese, et al.
(författare)
-
The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.
- 2019
-
Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 34:2, s. 191-209
-
Tidskriftsartikel (refereegranskat)abstract
- To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n = 1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5 years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.
|
|
| 9. |
- Wan, Y., et al.
(författare)
-
Design, synthesis, and biological evaluation of the first selective nonpeptide AT2 receptor agonist
- 2004
-
Ingår i: J Med Chem. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 47:24, s. 5995-6008
-
Tidskriftsartikel (refereegranskat)abstract
- The first druglike selective angiotensin II AT(2) receptor agonist (21) with a K(i) value of 0.4 nM for the AT(2) receptor and a K(i) > 10 microM for the AT(1) receptor is reported. Compound 21, with a bioavailability of 20-30% after oral administration and a half-life estimated to 4 h in rat, induces outgrowth of neurite cells, stimulates p42/p44(mapk), enhances in vivo duodenal alkaline secretion in Sprague-Dawley rats, and lowers the mean arterial blood pressure in anesthetized, spontaneously hypertensive rats. Thus, the peptidomimetic 21 exerts a similar biological response as the endogenous peptide angiotensin II after selective activation of the AT(2) receptor. Compound 21, derived from the prototype nonselective AT(1)/AT(2) receptor agonist L-162,313 will serve as a valuable research tool, enabling studies of the function of the AT(2) receptor in more detail.
|
|
| 10. |
- Accordini, S., et al.
(författare)
-
A three-generation study on the association of tobacco smoking with asthma
- 2018
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 47:4, s. 1106-1117
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Mothers' smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers' smoking may have a similar effect, and biological plausibility that fathers' smoking during adolescence may influence offspring's health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma. Methods: Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged <= 51 years) had ever had asthma and whether it had coexisted with nasal allergies or not. Mothers and fathers also provided information on their parents' (grandparents) and their own asthma, education and smoking history. Multilevel mediation models within a multicentre three-generation framework were fitted separately within the maternal (4666 offspring) and paternal (4192 offspring) lines. Results: Fathers' smoking before they were 15 [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI): 1.01-2.01] and mothers' smoking during pregnancy (RRR = 1.27, 95% CI: 1.01-1.59) were associated with asthma without nasal allergies in their offspring. Grandmothers' smoking during pregnancy was associated with asthma in their daughters [odds ratio (OR) = 1.55, 95% CI: 1.17-2.06] and with asthma with nasal allergies in their grandchildren within the maternal line (RRR = 1.25, 95% CI: 1.02-1.55). Conclusions: Fathers' smoking during early adolescence and grandmothers' and mothers' smoking during pregnancy may independently increase asthma risk in offspring. Thus, risk factors for asthma should be sought in both parents and before conception.
|
|
