Effects of sex and estrogen on chicken ductus arteriosus reactivity.

Sex hormones have an important influence on cardiovascular physiology and pathophysiology and sex differences in vascular reactivity have been widely demonstrated. In the present study we hypothesized 1) the presence of sexual dimorphism in chicken ductus arteriosus (DA) responsiveness to contractile and relaxant stimuli and 2) that estrogens are vasoactive in the chicken DA. In vitro contractions (assessed with a wire myograph) induced by normoxia, KCl, 4-aminopyridine, norepinephrine, phenylephrine, U46619, or endothelin-1, as well as relaxations induced by ACh, sodium nitroprusside, BAY 41-2272, PGE(2), isoproterenol, forskolin,Y-27632, and hydroxyfasudil were not significantly different between males and females. The estrogen 17beta-estradiol elicited concentration-dependent relaxation of KCl-, phenylephrine-, and oxygen-induced active tone in male and female chicken DA. The stereoisomer 17alpha-estradiol showed lesser relaxant effects, and the selective estrogen receptor (ER) agonists 4,4',4''-(4-propyl-[(1)H]pyrazole-1,3,5-triyl)tris-phenol (ERalpha) and 2,3-bis(4-hydroxyphenyl)-propionitrile (ERbeta) did not show any effect. There were no sex differences in the responses to estrogen. Endothelium removal or the presence of the soluble guanylate cyclase inhibitor ODQ, the K(+) channel blockers tetraethylammonium, glibenclamide, and charybdotoxin, or the ER antagonist fulvestrant did not modify 17beta-estradiol-induced relaxation. CaCl(2) (30 muM-10 mM) induced concentration-dependent contraction in DA rings depolarized by 62.5 mM KCl or stimulated with 21% O(2) in Ca(2+)-free medium. Preincubation with 17beta-estradiol or the L-type Ca(2+) channel blocker nifedipine produced an inhibition of CaCl(2)-induced contractions. In conclusion, there are no sex-related differences in chicken DA reactivity. The estrogen 17beta-estradiol induces an endothelium-independent relaxation of chicken DA that is not mediated by ER activation. This relaxant effect is, at least partially, due to inhibition of Ca(2+) entry from extracellular space.

Endothelium-dependent contraction induced by acetylcholine in the chicken ductus arteriosus involves cyclooxygenase-1 activation and TP receptor stimulation.

In numerous vascular beds, acetylcholine (ACh) evokes the simultaneous release of endothelium-derived relaxing and contracting factors (EDRF and EDCF, respectively). We aimed to determine whether ACh evokes the release of an EDCF in the chicken ductus arteriosus (DA) and to identify its nature. Isolated rings DA from 19-d chicken embryos (total incubation: 21-d) were studied in a wire myograph. Low concentrations of ACh (30 nM-1 microM) elicited a relaxation, which was followed by a contraction at higher concentrations (3 microM-0.1 mM). Both relaxation and contraction were abolished by removal of endothelium and were sensitive to the antimuscarinic agents atropine and 4-DAMP (M3-receptor antagonist). ACh-induced contraction was impaired in the presence of the non-selective inhibitor of cyclooxygenase (COX) indomethacin, the selective COX-1 inhibitor valeryl salicylate, and the thromboxane (TX)/prostaglandin (PG) H2 (TP) receptor blocker SQ-29458, whereas the response was not affected by the selective COX-2 inhibitor nimesulide, the TX synthase inhibitor furegrelate, the H2O2 scavenger PEG-catalase, the nitric oxide synthase inhibitor L-NAME, or the soluble guanylate cyclase inhibitor ODQ. Enzyme immunoassay determined that, under basal conditions, the chicken DA produced PGE2, PGF2alpha and TXB2 (stable metabolite of TXA2). Prostanoid production was inhibited by indomethacin but was not significantly affected by ACh. We conclude that in the chicken DA, stimulation of muscarinic receptors by ACh induces an endothelium-dependent relaxation followed by an endothelium-dependent contraction. The contraction involves COX-1 activation and TP receptor stimulation.

[A young boy with pulmonary tuberculosis]. / Een jong kind met pulmonale tuberculose.

BACKGROUND: Infectious pulmonary tuberculosis in young children is rare in the Netherlands. Young children with a tuberculosis infection are at high risk of developing miliary tuberculosis or tuberculous meningitis. CASE DESCRIPTION: A 12-month-old boy of Turkish descent was brought to our hospital because of coughing present for a few weeks and fever for 10 days. Nine weeks previously the patient had visited family in western Turkey, where, as far as is known, he did not come into contact with anyone who had tuberculosis. A chest X-ray showed infiltration of the middle lobe. He did not recover with empirical treatment for community-acquired pneumonia. Because of treatment failure, tuberculin skin testing was performed, the result of which was positive. The boy fully recovered during tuberculostatic treatment. Open tuberculosis was subsequently confirmed in a family member in Turkey after the boy's visit. CONCLUSION: In the event of pneumonia with an atypical course, testing for tuberculosis is justified, even if there is no or little likelihood of contact with a tuberculosis patient in the history.

Third-degree atrioventricular block in an adolescent following acute alcohol intoxication.

Alcohol abuse is a major problem among adolescents, and has both acute, potentially lethal, and long-term harmful effects. The authors describe an adolescent who was in a subcomatose condition after binge drinking. His serum alcohol concentration was 3.7 g/l. The next morning, before transfer to the paediatric ward, he developed a third-degree atrioventricular (AV) block without cardiac output while his infusion needle was removed. This recovered spontaneously after a precordial thump. Retrospectively, electrocardiography showed an increasing PR prolongation (200-300 ms) before the removal of the infusion needle. ECG recordings several hours later showed a first-degree AV block, which was no longer seen during follow-up, 1 month later. The authors conclude that acute alcohol poisoning has the potential to prolong the PR interval in young, healthy adolescents without pre-existing first-degree AV block and provoke a third-degree AV block after vagal stimulation. It is yet another potential danger of acute alcohol intoxication in this age group.