| 1. |
- Chan, K. Y., et al.
(författare)
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Characterization of the Calcitonin Gene-Related Peptide Receptor Antagonist Telcagepant (MK-0974) in Human Isolated Coronary Arteries
- 2010
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 1521-0103 .- 0022-3565. ; 334:3, s. 746-752
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Tidskriftsartikel (refereegranskat)abstract
- The sensory neuropeptide calcitonin gene-related peptide (CGRP) plays a role in primary headaches, and CGRP receptor antagonists are effective in migraine treatment. CGRP is a potent vasodilator, raising the possibility that antagonism of its receptor could have cardiovascular effects. We therefore investigated the effects of the antimigraine CGRP receptor antagonist telcagepant (MK-0974) [N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan- 3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)piperidine-1-c arboxamide] on human isolated coronary arteries. Arteries with different internal diameters were studied to assess the potential for differential effects across the coronary vascular bed. The concentration-dependent relaxation responses to human alpha CGRP were greater in distal coronary arteries (i.d. 600-1000 mu m; E-max = 83 +/- 7%) than proximal coronary arteries (i.d. 2-3 mm; E-max = 23 +/- 9%), coronary arteries from explanted hearts (i.d. 3-5 mm; E-max = 11 +/- 3%), and coronary arterioles (i.d. 200-300 mu m; E-max = 15 +/- 7%). Telcagepant alone did not induce contraction or relaxation of these coronary blood vessels. Pretreatment with telcagepant (10 nM to 1 mu M) antagonized alpha CGRP-induced relaxation competitively in distal coronary arteries (pA(2) = 8.43 +/- 0.24) and proximal coronary arteries and coronary arterioles (1 mu M telcagepant, giving pK(B) = 7.89 +/- 0.13 and 7.78 +/- 0.16, respectively). alpha CGRP significantly increased cAMP levels in distal, but not proximal, coronary arteries, and this was abolished by pretreatment with telcagepant. Immunohistochemistry revealed the expression and colocalization of the CGRP receptor elements calcitonin-like receptor and receptor activity-modifying protein 1 in the smooth muscle cells in the media layer of human coronary arteries. These findings in vitro support the cardiovascular safety of CGRP receptor antagonists and suggest that telcagepant is unlikely to induce coronary side effects under normal cardiovascular conditions.
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| 2. |
- Kimblad, Agnes, et al.
(författare)
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Decreased sperm counts in Swedish users of oral tobacco
- 2022
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Ingår i: Andrology. - : Wiley. - 2047-2919 .- 2047-2927. ; 10:6, s. 1181-1188
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoke-free tobacco via moist oral snuff (snus) is used daily in more than 20% of Swedish men. Negative effects of cigarette smoking on sperm parameters are well documented, unlike for snuff, despite relevance also for other smoke-free nicotine products. Objectives: We wanted to investigate whether reproductive parameters differed between users and non-users of snuff, and whether the amount of snuff and nicotine exposure mattered. Materials and methods: Men (n = 613) from the general population, recruited 2000–2010, were physically examined, answered questions on smoking and snuff use, and delivered urine, blood and semen samples. Sperm concentration, total sperm count, semen volume, percent morphologically normal and progressively motile sperm, and DNA fragmentation index (by the Sperm Chromatin Structure Assay) and reproductive hormones were analysed. Nicotine exposure was measured through urinary levels of cotinine. We used general linear models, with adjustments including cigarette smoking, and for semen parameters also abstinence time. Results: After adjustments, total sperm count was 24% lower (P = 0.03) and testosterone 14% higher (P < 0.001) in 109 users of snuff than in non-users, whereas cotinine was positively associated with testosterone and oestradiol (P < 0.001). Numbers of boxes of snuff used per week were associated with testosterone and FSH (P < 0.001). Discussion: Applied to the general population, the consumption of smoke-free tobacco by the use of snuff was associated with a lower sperm count and a higher testosterone, for which the extent seemed to play a role. Conclusions: Independent of smoking, consumption of snuff was associated with lower total sperm count and different hormone levels. Applying these results to a reported association between sperm count and the chance of pregnancy, men who used snuff would have about a 10% lower chance of fathering a child.
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| 3. |
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| 4. |
- Kimblad, H., et al.
(författare)
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Adult cardiac arrest in the emergency department - A Swedish cohort study
- 2022
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 175, s. 105-112
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiac arrests occurring in emergency departments (ED) represent 10-20% of all in-hospital cardiac arrests (IHCA). Yet few studies have examined the characteristics and outcomes of IHCA occurring in the ED. The aim was to describe this population in a nationwide registry covering all EDs in Sweden. Methods: Patients >= 18 years with an IHCA in the ED reported to the Swedish Registry for Cardio-Pulmonary Resuscitation (SRCR) during 2007-2018 were included. Descriptive statistics were calculated. Results: We identified 2,604 (10 % of all IHCA in SRCR) ED arrests; 902 (35%) survived to hospital discharge and 672 (75%) had good neurological outcomes (Cerebral Performance Category 1-2). The national incidence rate 2016-2018 was 1.6 (range 1.60-1.70) cardiac arrests per 10,000 ED visits. Over 90% were witnessed and 26% had a shockable first rhythm. Three presumed aetiologies together explained half of the cases; myocardial ischaemia (30%, n = 789), primary arrhythmia (12%, n = 327) and respiratory insufficiency (10%, n = 265). At a subset of ED arrest at Karolinska University Hospital, half of the cardiac arrests occurred within one hour from arrival to the ED. Conclusion: About 10% of all IHCA occurs in ED, however, from an ED perspective it is a rare event. Cardiac arrests in the ED generally occur within an hour from arrival to the ED. One in three survive to discharge from hospital and the majority of survivors have a good neurological outcome.
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