G-protein-coupled receptor function in heart failure.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
J Nienaber
Publications and source records attributed to J Nienaber.
Beta-adrenergic axis and heart disease.
Beta-adrenergic receptors (beta-ARs) belong to a large family of G-protein-coupled receptors (GPCRs) that form the interface between the sympathetic nervous system and the cardiovascular system. The beta-AR signal system is one of the most powerful regulators of cardiac function, mediated by the effects of the sympathetic transmitters epinephrine and norepinephrine. In a number of cardiac diseases, however, the biology of beta-AR signaling pathways is altered dramatically. Here we discuss the role of beta-AR signaling in the normal and abnormal heart and how the use of genetically engineered mouse models has helped in our understanding of the pathophysiology of cardiac disease.
Animals↗
Savignin, a potent thrombin inhibitor isolated from the salivary glands of the tick Ornithodoros savignyi (Acari: Argasidae).
A thrombin (E.C. 3.4.21.5) inhibitor, savignin, was isolated from the salivary glands of Ornithodoros savignyi by a combination of size exclusion, anion-exchange, and reversed-phase chromatography. The inhibitor has a molecular mass of 12,430.4 Da as determined by electrospray mass spectrometry. The behavior of savignin during anion-exchange chromatography indicated that it has an acidic pI. The available N-terminal sequence (residues 1-11) differed from that of ornithodorin with only one residue. Savignin inhibits thrombin-induced platelet aggregation, but has no effect on ADP- or collagen-induced aggregation. Kinetic studies indicated that savignin is a competitive, slow-, tight-binding inhibitor of alpha-thrombin (K(i) = 4.89 +/- 1.39 pM). Tight-binding kinetics showed that the inhibitor has a lower affinity for gamma-thrombin (K(i) = 22.3 +/- 5.9 nM). Plasmin, factor Xa, and trypsin are not inhibited by savignin.
Amino Acids↗
Fused 1,2-dithioles, V: Carbenoid anions as intermediates in reactions of pyrrothines and their heteroanalogues.
Pyrrothines like thiolutine and other bicyclic 1,2-dithioles of type 1 when unsubstituted in 3-position are marked by their CH acidity. In the presence of weak bases such as triethylamine the pyrrothine 4 degraded via its anion to a thioketene trapped as the 1,3-dithietane 5. The carbenoid anions of several compounds 1 reacted with elemental sulphur forming enthiolates whose alkylation led to the corresponding thioethers or, in the case of the thiolactam 9, to the bicyclic trithiones 10 and 11. In the same manner selenides can be obtained via intermediate selenolate ions. Introduction of an aryl- or heteroarylmercapto group into compounds 1 was achieved directly by reaction of the corresponding anions with suitable disulphides. Though there may be structural limitations, this sulphurization reaction can be extended to 3-unsubstituted trithiones. The new compounds exhibited significant activity against Mycobacterium tuberculosis in the primary screening.
Antitubercular Agents↗
Serum cortisol concentrations in gilts and sows housed in tether stalls, gestation stalls and individual pens.
Three experiments were conducted to determine whether housing in tether stalls, gestation stalls or individual pens imposes a stress upon gilts and sows. Changes in serum cortisol concentrations were used as the indicator for stress. In the first experiment, gilts were placed in tether stalls and individual pens to determine cortisol concentrations after tethering and to see if this response was different from gilts that were previously tethered for two weeks. In the second experiment, gilts were tethered in order to determine if penning in tether stalls altered the circadian rhythm of cortisol. In the third experiment, breeding sows were placed in tether stalls, gestation stalls or individual pens to determine if a ten-hour profile of cortisol concentrations were altered and if such housing affected a sow's response to transfer to farrowing crates. The results indicate that the initial response to tethering varied among gilts and sows and this variation appeared to be due to previous penning and human handling experiences. When tethering was stressful, acclimation required up to four days. However, once acclimated, tethering resulted in higher morning concentrations which may be associated with the greater activity that occurs at this time. Housing in tether stalls, gestation stalls or individual pens was not a stress for breeding sows and did not alter sows' responses to transfer into the farrowing crate.
Animals↗