PubMed Health⌕ Search

Biomedical subjects

D Kon

Publications and source records attributed to D Kon.

5 recordsLinked to original sources
PubMed2001

Doxazosin inhibits monocyte chemotactic protein 1-directed migration of human monocytes.

Monocyte chemotactic protein 1 (MCP-1)-directed transendothelial migration of monocytes plays a key role in the early development of atherosclerosis. Migration of monocytes requires degradation of extracellular matrices, a process that involves matrix metalloproteinases (MMP) and tissue inhibitors of MMPs (TIMP). Recent studies suggest that the alpha1-adrenergic receptor antagonist doxazosin (Dox) might have antiatherosclerotic effects, although the underlying mechanisms are poorly understood. The purpose of the present study was to determine the effects of Dox on MCP-1-directed monocyte migration, MMP-9 activity, and TIMP-1 expression. MCP-1 (50 ng/ml) stimulated migration of human peripheral blood monocytes (HPBM) 2.7+/-0.42-fold and THP-1 human monocytes 5.9+/-0.83-fold compared with unstimulated control. Dox inhibited MCP-1-induced migration in a dose-dependent manner, with a maximal reduction at 10 microM of 69.5+/-5.9% in HPBM and 72.2+/-3.2% in THP-1 cells. Dox blocked migration even after pretreatment with phenoxybenzamine, an irreversible alpha1-adrenergic receptor antagonist (HPBM: phenoxybenzamine 1 microM + Dox 10 microM, 71.9+/-2.2% inhibition; THP-1 cells: phenoxybenzamine 1 microM + Dox 10 microM: 78+/-7.7% inhibition), suggesting that the antimigratory activity of Dox is mediated through a novel mechanism unrelated to its blocking of the alpha1-adrenergic receptor. Dox (10 microM) inhibited MMP-9 activity by 67.6+/-10.5%, whereas MMP-9 protein levels were not affected. Also, Dox increased PMA-induced-tissue inhibitor of MMPs-1 (TIMP-1) expression by 134.4+/-6.6%. Dox 10 microM. The present study demonstrates a potential novel antiatherosclerotic action of Dox by blocking MCP-1-directed monocyte migration, which might be partly mediated by inhibition of MMP-9 activity.

Adrenergic alpha-Antagonists↗
PubMed1988

Clutter interference along the target range axis in the echolocating bat, Eptesicus fuscus.

The sensitivity of the echolocating bat, Eptesicus fuscus, for detection of a sonar target is impaired by the presence of additional targets located at similar distances. At a range of 54 cm, sensitivity to one target declines if the range separation to other targets is smaller than 8-9 cm. This loss of sensitivity is an example of clutter interference along the range axis, created by simultaneous masking of one set of echoes by another. Echoes that fall within an experimentally defined critical range band may sum together to contribute collectively to detection in that band. Echoes falling into separate bands may be detected independently. Acoustic glints within a band appear to be grouped together to be perceived as a single range-extended target of complex structure. Range bands may thus define what a "target" is by specifying within-target and between-target differences in range. The width of critical range bands appears to depend upon target range, with wider bands at greater ranges.

Animals↗
PubMedDate not supplied

Thrombosis of mitral valve prosthesis presenting as abdominal pain.

A 67-year-old woman presented with abdominal pain, anemia, and leukocytosis. Five years previously, the patient had undergone mitral valve replacement with a St. Jude bileaflet mechanical prosthesis. After her admission, echocardiography confirmed an immobile leaflet of the prosthetic valve. At urgent surgery, thrombosis and pannus, obstructing the disc, were found, and the mechanical valve was replaced with a bioprosthesis. The incidence of mitral valve thrombosis is low, ranging from 0.1% to 5.7% per patient per year. Patients who receive inadequate anticoagulation, particularly with valve prostheses in the mitral position, have an increased risk for thrombus or pannus formation. Presentation varies, from symptoms of congestive heart failure or systemic embolization, to fever or no symptoms. New or worsening symptoms in a patient with a prosthetic heart valve should raise concerns about prosthetic dysfunction. Aggressive investigation and, if indicated, urgent or emergency surgery for treatment can be lifesaving.

Abdominal Pain↗