Compensatory up-regulation of angiotensin II subtype 1 receptors in alpha ENaC knockout heterozygous mice.

BACKGROUND: In mice, a partial loss of function of the epithelial sodium channel (ENaC), which regulates sodium excretion in the distal nephron, causes pseudohypoaldosteronism, a salt-wasting syndrome. The purpose of the present experiments was to examine how alpha ENaC knockout heterozygous (+/-) mice, which have only one allele of the gene encoding for the alpha subunit of ENaC, control their blood pressure (BP) and sodium balance. METHODS: BP, urinary electrolyte excretion, plasma renin activity, and urinary adosterone were measured in wild-type (+/+) and heterozygous (+/-) mice on a low, regular, or high sodium diet. In addition, the BP response to angiotensin II (Ang II) and to Ang II receptor blockade, and the number and affinity of Ang II subtype 1 (AT1) receptors in renal tissue were analyzed in both mouse strains on the three diets. RESULTS: In comparison with wild-type mice (+/+), alpha ENaC heterozygous mutant mice (+/-) showed an intact capacity to maintain BP and sodium balance when studied on different sodium diets. However, no change in plasma renin activity was found in response to changes in sodium intake in alpha ENaC +/- mice. On a normal salt diet, heterozygous mice had an increased vascular responsiveness to exogenous Ang II (P < 0.01). Moreover, on a normal and low sodium intake, these mice exhibited an increase in the number of AT1 receptors in renal tissues; their BP lowered markedly during the Ang II receptor blockade (P < 0.01) and there was a clear tendency for an increase in urinary aldosterone excretion. CONCLUSIONS: alpha ENaC heterozygous mice have developed an unusual mechanism of compensation leading to an activation of the renin-angiotensin system, that is, the up-regulation of AT1 receptors. This up-regulation may be due to an increase in aldosterone production.

Interpreting Breast International Group (BIG) 1-98: a randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer.

The Breast International Group (BIG) 1-98 study is a four-arm trial comparing 5 years of monotherapy with tamoxifen or with letrozole or with sequences of 2 years of one followed by 3 years of the other for postmenopausal women with endocrine-responsive early invasive breast cancer. From 1998 to 2003, BIG -98 enrolled 8,010 women. The enhanced design f the trial enabled two complementary analyses of efficacy and safety. Collection of tumor specimens further enabled treatment comparisons based on tumor biology. Reports of BIG 1-98 should be interpreted in relation to each individual patient as she weighs the costs and benefits of available treatments. Clinicaltrials.gov ID: NCT00004205.

Attachés d'administration centrale. Constitution initiale des nouveaux corps . [Instruction du 11 avril 1956 des secrétaires d'Etat au Budget et à la présidence du conseil (Fonction publique) relative à la constitution initiale des nouveaux corps d'attachés d'administration. - Annexes. I. Programme des matières à option "Administration générale" du concours spécial prévu à l'article 23 ; II. Textes de base : Loi du 3 février 1953 et du 3 avril 1955. Décret du 16 décembre 1955 portant règlement d'administration publique relatif au statut particulier des attachés d'administration centrale. III. Organisation et programme du concours normal prévu aux articles 5 et 12 du décret du 16 décembre 1955.]

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Kehä III:n varrelta : 20 vuotta vantaalaista ammattiteatteria

Vantaan ensimmäinen, ja edelleen ainoa ammattimainen puheteatteri Teatteri Kehä III perustettiin vuonna 1986. Teatteri Kehä III on ensimmäisiä ns. vapaita teatteriryhmiä, jotka halusivat itse päättää mitä esitetään, missä ja kenelle. Tärkeää oli, että jokainen teatterissa toimiva voi taiteellisesti sitoutua lopputulokseen. Pienen teatterin pyörittäminen on vaatinut sinnikkyyttä, kekseliäisyyttä, ja uskoa teatterin tarpeellisuuteen. Pienuudestaan huolimatta Teatteri Kehä III ei ole pelännyt ottaa suuria taiteellisia ja taloudellisia riskejä. Oman tilan kunnostaminen vuonna 1995 tyhjillään olleeseen Tikkurilan Silkkitehtaaseen ilman yhteiskunnallista tukea oli rohkea, ja ihailua herättävä kulttuuriteko. Teatteri Kehä III on kantaesittänyt suuren joukon eurooppalaisia näytelmiä, ja ollut usein aikaansa edellä mitä esitysten teemoihin tulee. Yhtenä motiivina kokeellisillekin tuotannoille on ollut apurahojen saanti; uudet tekstit ja ideat kun ovat saaneet helpommin tukea. Pienten teattereiden suurin ongelma on ainainen rahanpuute. Tämän historiikin kokoamista varten olen käynyt läpi Teatteri Kehä III:n arkistoja: lukenut kokousten pöytäkirjoja ja toimintasuunnitelmia, sekä tutkinut teatterin vuosikirjoja ja esitysten käsiohjelmia. Olen myös haastatellut vuosien varrella Teatteri Kehä III:ssa toimineita ihmisiä. Teatteri Kehä III:n tuottamien esitysten määrä suuri ja hyvin monipuolinen, siksi keskityn käsittelemään teatterin elinkaarta sen ohjelmiston kautta. Teatteri Kehä III juhli 20-vuotista taivaltaan marraskuussa 2006, ja vaihtoi samalla nimensä Teatteri Vantaaksi.

Angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors.

Angio-oedema (AE) is a known adverse effect of angiotensin converting enzyme inhibitor (ACE-I) therapy. Over the past several decades, evidence of failure to diagnose this important and potentially fatal reaction is commonly found in the literature. Because this reaction is often seen first in the primary care setting, a review was undertaken to analyse and document the keys to both diagnostic criteria as well as to investigate potential risk factors for ACE-I AE occurrence. A general review of published literature was conducted through Medline, EMBASE, and the Cochrane Database, targeting ACE-I-related AE pathomechanism, diagnosis, epidemiology, risk factors, and clinical decision making and treatment. The incidence and severity of AE appears to be on the rise and there is evidence of considerable delay in diagnosis contributing to significant morbidity and mortality for patients. The mechanism of AE due to ACE-I drugs is not fully understood, but some genomic and metabolomic information has been correlated. Additional epidemiologic data and clinical treatment outcome predictors have been evaluated, creating a basis for future work on the development of clinical prediction tools to aid in risk identification and diagnostic differentiation. Accurate recognition of AE by the primary care provider is essential to limit the rising morbidity associated with ACE-I treatment-related AE. Research findings on the phenotypic indicators relevant to this group of patients as well as basic research into the pathomechanism of AE are available, and should be used in the construction of better risk analysis and clinical diagnostic tools for ACE-I AE.

Immunomarquage des collagènes I, III et IV, de la laminine et de la fibronectine dans la capsule cristallinienne humaine [Immunolabelling of collagen types I, III and IV, laminin and fibronectin in the human lens capsule].

PURPOSE: To localize collagen types I, III, and IV, laminin and fibronectin in the anterior human lens capsule. MATERIAL AND METHODS: Twenty-one anterior capsules were sampled by capsulorhexis during extracapsular cataract extraction (mean age 71.5). All capsules were labelled by an immunostaining specific for each antibodies. Immunostaining of four capsules was revealed with immunoperoxydase and seventeen using indirect immunofluorescence. RESULTS: Labelling of collagen types I and III was observed throughout the entire thickness of the capsule for each technique, the strongest labelling was found in the base of the epithelial cells with immunofluorescence. Collagen type IV was observed at the base of the epithelial cells whichever technique was used. Laminin could be detected in the inner layer of the capsule, using immunoperoxydase or immunofluorescence. No specific labelling was found for fibronectin using the two techniques. CONCLUSIONS: Different kinds of collagens have been found in capsules, more particularly the type III. The latter does not appear on other ocular basement membrane. Because of this uneven distribution in the capsule's thickness, each collagen might have a specific function.