Cholesteryl ester accumulation and accelerated cholesterol absorption in intestine-specific hormone sensitive lipase-null mice

Hormone sensitive lipase (HSL) regulates the hydrolysis of acylglycerols and cholesteryl esters (CE) in various cells and organs, including enterocytes of the small intestine. The physiological role of this enzyme in enterocytes, however, stayed elusive. In the present study we generated mice lacking HSL exclusively in the small intestine (HSLiKO) to investigate the impact of HSL deficiency on intestinal lipid metabolism and the consequences on whole body lipid homeostasis. Chow diet-fed HSLiKO mice showed unchanged plasma lipid concentrations. In addition, feeding with high fat/high cholesterol (HF/HC) diet led to unaltered triglyceride but increased plasma cholesterol concentrations and CE accumulation in the small intestine. The same effect was observed after an acute cholesterol load. Gavaging of radioactively labeled cholesterol resulted in increased abundance of radioactivity in plasma, liver and small intestine of HSLiKO mice 4h post-gavaging. However, cholesterol absorption determined by the fecal dual-isotope ratio method revealed no significant difference, suggesting that HSLiKO mice take up the same amount of cholesterol but in an accelerated manner. mRNA expression levels of genes involved in intestinal cholesterol transport and esterification were unchanged but we observed downregulation of HMG-CoA reductase and synthase and consequently less intestinal cholesterol biosynthesis. Taken together our study demonstrates that the lack of intestinal HSL leads to CE accumulation in the small intestine, accelerated cholesterol absorption and decreased cholesterol biosynthesis, indicating that HSL plays an important role in intestinal cholesterol homeostasis.

Pharmacological characterization of nipecotic acid ethyl ester: A novel cholinergic muscarinic agonist

The aim of this dissertation was to examine the hypothesis that (R)-nipecotic acid ethyl ester ((R)-NAEE) is a cholinergic agonist that is selective for a particular subclass (M$\sb1$ or M$\sb2$) of muscarinic receptors.^ Ligand binding studies indicated that like cholinergic agonists (R)-NAEE selectively interacts with rat heart (M$\sb2$) and brain (M$\sb1$) muscarinic binding sites. Physiological studies revealed that unlike cholinergic agonists (R)-NAEE stimulated only those responses coupled to M$\sb2$ muscarinic receptors (acid secretion, negative inotropic response, smooth muscle contraction). Moreover, in rat brain (R)-NAEE differentiated between M$\sb2$ receptors negatively coupled to adenylate cyclase activity and M$\sb1$ receptors mediating PI turnover, being a weak competitive antagonist at these latter sites. In isolated rat gastric mucosal cells (R)-NAEE also differentiated between two M$\sb2$ coupled responses where it potentiated acid secretion but could not stimulate PI turnover. Atropine, a selective antimuscarinic agent, competitively antagonized all agonist effects of (R)-NAEE.^ Unlike (R)-NAEE, the muscarinic agonist arecoline, which is structurally similar to (R)-NAEE, stimulates both M$\sb1$ and M$\sb2$ receptors. Structure activity studies revealed that saturation of the piperidine ring and the length of the ester side chain of (R)-NAEE are the most important determinants for both M$\sb2$ efficacy and selectivity.^ The results of this dissertation establish that (R)-NAEE is a cholinergic muscarinic receptor agonist that displays greater efficacy at M$\sb2$ than at M$\sb1$ receptors, being a weak antagonist at the M$\sb1$ site. With such selectivity, (R)-NAEE may be regarded as a prototype for a unique class of cholinergic muscarinic M$\sb2$ receptor agonists. Because of these unique properties, (R)-NAEE should be useful in the further characterization of muscarinic receptors, and could lead to the development of a new class of therapeutic agents. ^

Tor Ester : Mittel gegen die falschen Blutbeschuldigungen

von M. Duschak

Discorso accademico del Rabbi Tranquillo Vita Corcos fatto recitare dalli giovani della sua Accdemia in occasione della festività degli Ebrei per l'historia d'Ester, e Mordacheo nell'anno 5470. dalla creazione del mondo

Im Freimann-Katalog Teil der Sammelmappe "Schriften zur Geschichte der Juden in Rom, 1697-1890"

Erreṭung der judn durch Ester und Mordechai : troier špihl und freidliches ende in 5 teihlin ...

in der reine oif richṭige ṭaiṭš šprache ... Ja'akov Ben-... Jeḥzki'el mip-Puzn

Sēfer Mēṣaḥ Ahārôn : ʿal megillôt Estēr, targûm rîšôn we-targûm šēnî ; dś iz warn gmachṭ oif megiles Ester un ali guṭ ṭaiṭš gšṭelṭ

[Aharon Ben-Mordechai aus Rödelheim]

Ester oder di belohnṭe ṭugend : eine pozze in fier abšniṭṭen nebzṭ einigen noch nichṭ gedrukṭen gedichṭen in jidiš-daiṭšer mundarṭ

fon Josef Hertz

Sēfer Mēṣaḥ Ahārôn : ʿal megillôt Estēr, targûm rîšôn we-targûm šēnî ; dś iz war gimachṭ oif megiles Ester ... alz guṭ ṭaiṭš gšṭelt ...

[Aharon Ben-Mordechai aus Rödelheim]

Ester oder di belohnṭe ṭugend : in 4 abšniṭṭen in jidiš-ṭaiṭšer mundorṭ

fon Josef Herz