Ovlivněním metabolizmu lipidů urychluje hypotyreóza proces aterogeneze a zvyšuje kardiovaskulární riziko. U manifestní hypotyreózy klesá počet LDL-receptorů v játrech a dochází ke zvýšení celkového cholesterolu, LDL-cholesterolu a apolipoproteinu B v krvi. HDL částice bývají normální, nebo dokonce lehce zvýšené z důvodu snížené aktivity cholesteryl-ester transfer proteinu (CETP) a jaterní lipázy. To vede k redukci transportu esterů cholesterolu z HDL-(2) do VLDL a IDL. Podobně subklinická hypotyreóza má na lipidogram nepříznivý vliv, vede však spíše k proaterogenním změnám poměru lipidových částic než k vzestupu celkového cholesterolu. Subklinická hypotyreóza vede k manifestaci některých rizikových faktorů aterosklerózy. I když studie hodnotící celkovou mortalitu a kardiovaskulární morbiditu nepřinesly zcela jednoznačné závěry, můžeme zvýšené kardiovaskulární riziko považovat i u subklinické hypotyreózy spíše za pravděpodobné. Otevřenou zůstává otázka, zda léčba subklinické hypotyreózy levotyroxinem toto riziko snižuje. K dispozici máme zatím jen nepřímé důkazy získané studiemi, které hodnotily vliv léčby levotyroxinem na rizikové faktory aterosklerózy. Zahájení hypolipidemické farmakoterapie (především statiny) u (sub)klinické hypotyreózy je však velmi rizikové z hlediska rozvoje či zhoršení myopatie, což je další pádný důvod pro aktivní screening a léčbu (sub)klinické hypotyreózy u všech pacientů s dyslipidemiemi., Jan Jiskra, Zdeňka Límanová, M. Antošová, and Lit. 33
This article refers to the rich vegetation on the rocky slopes along the Achensee (Tyrol, Northern calcareous Alps, Karwendelalpen) described by Professor Anton Kerner 150 years ago. The vegetation today is much less diverse, the subalpine species abundant in the last centuries are absent while the species of mixed mountainous forest prevail. The abundance of the Heather (Calluna vulgaris), which was not mentioned by A. Kerner, may indicate acidification due to acid rain. And the retreat of subalpine species may indicate the on going change to a warmer climate. and Jarmila Kubíková.
The contraction of gastrointestinal (GI) smooth muscles is
regulated by both Ca2+-dependent and Ca2+ sensitization
mechanisms. Proline-rich tyrosine kinase 2 (Pyk2) is involved in
the depolarization-induced contraction of vascular smooth muscle
via a Ca2+ sensitization pathway. However, the role of Pyk2
in GI smooth muscle contraction is unclear. The spontaneous
contraction of colonic smooth muscle was measured by using
isometric force transducers. Protein and phosphorylation levels
were determined by using western blotting. Pyk2 protein was
expressed in colonic tissue, and spontaneous colonic contractions
were inhibited by PF-431396, a Pyk2 inhibitor, in the presence of
tetrodotoxin (TTX). In cultured colonic smooth muscle cells
(CSMCs), PF-431396 decreased the levels of myosin light chain
(MLC20) phosphorylated at Ser19 and ROCK2 protein expression,
but myosin light chain kinase (MLCK) expression was not altered.
However, Y-27632, a Rho kinase inhibitor, increased
phosphorylation of Pyk2 at Tyr402 and concomitantly decreased
ROCK2 levels; the expression of MLCK in CSMCs did not change.
The expression of P(Tyr402)-Pyk2 and ROCK2 was increased
when CSMCs were treated with Ach. Pyk2 is involved in the
process of colonic smooth muscle contraction through the
RhoA/ROCK pathway. These pathways may provide very
important targets for investigating GI motility disorders.
Incubation of maize NADP-malic enzyme with tetranitromethane (TNM) resulted in a total loss of enzyme activity. The loss of enzyme activity was not observed at pH 6.3 but at pH 8.0. NADP-malic enzyme was inactivated to almost 90 % by incubation with an 80-fold molar excess of TNM for 5 min at 30 °C. The substrate malate or Mg2+ alone gave no protection, while NADP provided considerable protection. NADP in the presence of malate and Mg2+ totally protected the enzyme activity, suggesting that tyrosine residue may be located at or near the active site of maize NADP-malic enzyme. The spectral analysis of the modified enzyme indicated that modification of at least one tyrosine residue per subunit resulted in complete loss of the enzyme activity. The fluorescence study of unmodified and modified enzymes postulated that essential tyrosine residue at maize NADP-malic enzyme is possibly involved in malate binding. and S. R. Rao, B. G. Kamath, A. S. Bhagwat.