Furosemide inhibits 11beta-hydroxysteroid dehydrogenase type 2.

11Beta-hydroxsteroid dehydrogenase 2 (11beta-OHSD2) protects the nonselective renal mineralocorticoid receptor from the endogenous glucocorticoid cortisol. Thus, drugs inhibiting 11beta-OHSD2 might enhance urinary loss of potassium. As diuretics influence the renal handling of potassium, we analyzed the impact of 13 commonly used diuretics on 11beta-OHSD2. Furosemide was the only inhibitor. Its inhibition constant (Ki) was 30 micromol when extracts from COS-1 cells transfected with human 11beta-OHSD2 were used as an enzyme source. The type of inhibition was competitive. To establish whether furosemide inhibits 11beta-OHSD2 and 11beta-OHSD1 in the renal target tissue, isolated tubular segments from rats were analyzed. Furosemide decreased the oxidative activity of 11beta-OHSD2 in intact distal tubules and 11beta-OHSD1 in proximal convoluted tubules. For the assessment of furosemide on the excretion of corticosterone metabolites in vivo, rats were given furosemide i.p., and the ratio of tetrahydrocorticosterone plus 5alpha-tetrahydrocorticosterone to 11-dehydrotetrahydrocorticosterone was determined in urine. This ratio increased after the administration of furosemide in all animals, indicating inhibition of the oxidative activity of 11beta-OHSD. Thus, furosemide inhibits the 11beta-OHSD2 enzyme in the target tissue and might by that mechanism enhance the mineralocorticoid effect of 11beta-hydroxyglucocorticoids.

Die Geschichten der heiligen Schriften mit vielen Nutzanwendungen für die jisraelitische Jugend jedes Alters in Schule und Haus : mit 1 Zeittaf. u. 1 Charte d. heiligen Landes

von J. H. Hirsch

Jüdische Geschichte von der Zerstörung des 1. Tempels bis zur Gegenwart in Charakterbildern dargest.

von S. Müller

Jüdische Geschichte von der Zerstörung des 1. Tempels bis zur Gegenwart in Charakterbildern dargest.

von S. Müller

Aufrichtig und unpartheyische Prüfung des Dreyfachen Beweißes 1. Daß die Promotion e. Juden zum Docter Medicinae gegen die Christliche Religion ... seye, 2. Daß die jüdische Medici sehr schädl., u. unter Christen nicht zu dulden seyn, 3. Daß ein Christen Patient ... in e. jüdischen Medici Cur sich nicht begeben könne

dargethan von Johann Helfrich Sagittario u. untersucht durch Johann Friderich Rübel

Mus Hs 771 - No 1.: während der Reise : im Auftrag S:. Ehrw:. M: v.: St. componirte ich diese zwei Lieder zum 2ten Grad um, und [unleserlich] führte selbige den 27ten August 5830 [!], zum erstenmale aus. in [Stein als ein Symbol für Freimaurerei] Socrates

[Carl Oestreich]

Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages.

Precise knowledge regarding cellular uptake of nanoparticles is of great importance for future biomedical applications. Four different endocytotic uptake mechanisms, that is, phagocytosis, macropinocytosis, clathrin- and caveolin-mediated endocytosis, were investigated using a mouse macrophage (J774A.1) and a human alveolar epithelial type II cell line (A549). In order to deduce the involved pathway in nanoparticle uptake, selected inhibitors specific for one of the endocytotic pathways were optimized regarding concentration and incubation time in combination with fluorescently tagged marker proteins. Qualitative immunolocalization showed that J774A.1 cells highly expressed the lipid raft-related protein flotillin-1 and clathrin heavy chain, however, no caveolin-1. A549 cells expressed clathrin heavy chain and caveolin-1, but no flotillin-1 uptake-related proteins. Our data revealed an impeded uptake of 40 nm polystyrene nanoparticles by J774A.1 macrophages when actin polymerization and clathrin-coated pit formation was blocked. From this result, it is suggested that macropinocytosis and phagocytosis, as well as clathrin-mediated endocytosis, play a crucial role. The uptake of 40 nm nanoparticles in alveolar epithelial A549 cells was inhibited after depletion of cholesterol in the plasma membrane (preventing caveolin-mediated endocytosis) and inhibition of clathrin-coated vesicles (preventing clathrin-mediated endocytosis). Our data showed that a combination of several distinguishable endocytotic uptake mechanisms are involved in the uptake of 40 nm polystyrene nanoparticles in both the macrophage and epithelial cell line.

Hilkot 'eglah 'arufah : sive de veterum Hebraeorum circa vitulam decollandam ritibus, ex Deut. XXI. v. 1. seqq.

Leipzig, Univ., Diss., 1696

The Silencing of N-myc Downstream-Regulated Gene-1 in an Orthotopic Pancreatic Cancer Model Leads to More Aggressive Tumor Growth and Metastases

BACKGROUND: The understanding of molecular mechanisms leading to poor prognosis in pancreatic cancer may help develop treatment options. N-myc downstream-regulated gene-1 (NDRG1) has been correlated to better prognosis in pancreatic cancer. Therefore, we thought to analyze how the loss of NDRG1 affects progression in an orthotopic xenograft animal model of recurrence. METHODS: Capan-1 cells were silenced for NDRG1 (C(sil)) or transfected with scrambled shRNA (C(scr)) and compared for anchorage-dependent and anchorage-independent growth, invasion and tube formation in vitro. In an orthotopic xenograft model of recurrence tumors were grown in the pancreatic tail. The effect of NDRG1 silencing was evaluated on tumor size and metastasis. RESULTS: The silencing of NDRG1 in Capan-1 cells leads to more aggressive tumor growth and metastasis. We found faster cell growth, double count of invaded cells and 1.8-fold increase in tube formation in vitro. In vivo local tumors were 5.9-fold larger (p = 0.006) and the number of metastases was higher in animals with tumors silenced for NDRG1 primarily (3 vs. 1.1; p = 0.005) and at recurrence (3.3 vs. 0.9; p = 0.015). CONCLUSION: NDRG1 may be an interesting therapeutic target as its silencing in human pancreatic cancer cells leads to a phenotype with more aggressive tumor growth and metastasis.

Der lexikalische Ertrag der Konjekturalkritik von Jesaja Kap. 1-12

Bern, Phil. Diss., 1916

Libanon : exegetisch-homiletischer Kommentar zu den Psalmen ; Erster Teil: Buch 1. und 2.

von Josef Nobel

Josua, Richter, 1. u. 2. Samuelis

Josua, Richter, erster und zweiter Samuelis

Das Spruchbuch nach Saadja : ein Auszug aus Saadja's Kitab ṭalab al-ḥikma, Cap. 1-9 : als Beitrag zur Geschichte der Bibelauslegung

Halle-Wittenberg, Univ., Diss., 1888