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Biomedical subjects

J Bent

Publications and source records attributed to J Bent.

6 recordsLinked to original sources
PubMed2006

Characterization of a selective and potent antagonist of human P2X(7) receptors, AZ11645373.

BACKGROUND AND PURPOSE: The ATP-gated P2X(7) receptor has been shown to play a role in several inflammatory processes, making it an attractive target for anti-inflammatory drug discovery. We have recently identified a novel set of cyclic imide compounds that inhibited P2X(7) receptor-mediated dye uptake in human macrophage THP-1 cells. In this study the actions and selectivity of one of these compounds, AZ11645373, were characterized. EXPERIMENTAL APPROACH: We measured membrane currents, calcium influx, and YOPRO-1 uptake from HEK cells expressing individual P2X receptors, and YOPRO1 uptake and interleukin-1beta release from THP-1 cells in response to ATP and the ATP analogue benzoylbenzoyl ATP (BzATP). KEY RESULTS: AZ11645373 up to 10 microM, had no agonist or antagonist actions on membrane currents due to P2X receptor activation at human P2X(1), rat P2X(2), human P2X(3), rat P2X(2/3), human P2X(4), or human P2X(5) receptors expressed in HEK cells. AZ11645373 inhibited human P2X(7) receptor responses in HEK cells in a non-surmountable manner with K (B) values ranging from 5 - 20 nM, with mean values not significantly different between assays. K (B) values were not altered by removing extracellular calcium and magnesium. ATP-evoked IL-1beta release from lipopolysaccharide-activated THP-1 cells was inhibited by AZ11645373, IC(50) = 90 nM. AZ11645373 was > 500-fold less effective at inhibiting rat P2X(7) receptor-mediated currents with less than 50% inhibition occurring at 10 microM. CONCLUSIONS AND IMPLICATIONS: AZ11645373 is a highly selective and potent antagonist at human but not rat P2X(7) receptors and will have much practical value in studies of human cells.

Adenosine Triphosphate↗
PubMed2003

Novel P2X7 receptor antagonists.

The synthesis and pharmacological evaluation of a new series of potent P2X(7) receptor antagonists is disclosed. The compounds inhibit BzATP-mediated pore formation in THP-1 cells. The distribution of the P2X(7) receptor in inflammatory cells, most notably the macrophage, mast cell and lymphocyte, suggests that P2X(7) antagonists have a significant role to play in the treatment of inflammatory disease.

Adenosine Triphosphate↗
PubMed2003

Neutron-mapping polymer flow: scattering, flow visualization, and molecular theory.

Flows of complex fluids need to be understood at both macroscopic and molecular scales, because it is the macroscopic response that controls the fluid behavior, but the molecular scale that ultimately gives rise to rheological and solid-state properties. Here the flow field of an entangled polymer melt through an extended contraction, typical of many polymer processes, is imaged optically and by small-angle neutron scattering. The dual-probe technique samples both the macroscopic stress field in the flow and the microscopic configuration of the polymer molecules at selected points. The results are compared with a recent "tube model" molecular theory of entangled melt flow that is able to calculate both the stress and the single-chain structure factor from first principles. The combined action of the three fundamental entangled processes of reptation, contour length fluctuation, and convective constraint release is essential to account quantitatively for the rich rheological behavior. The multiscale approach unearths a new feature: Orientation at the length scale of the entire chain decays considerably more slowly than at the smaller entanglement length.

Journal Article↗
PubMed1984

Evaluation of a rapid method for the detection of vaginal group B streptococci in women in labor.

Group B streptococci infection is an important cause of neonatal morbidity and mortality. Effective therapeutic intervention has been prevented to date by our inability to rapidly detect vaginal colonization. Material obtained from the lower vagina of 414 women in labor was cultured, incubated in modified Islam serum starch broth and observed on the ward for the production of orange carotenoid pigment specific for group B streptococci. Subcultures yielded 48 true group B streptococci-positive results. For the Islam broth, the pigment appeared in 2 to 22.5 hours (median, 12.5 hours). The test was shown to have a sensitivity of 96% and a specificity of 100% for group B streptococci. This study demonstrated a simple inexpensive method of detecting vaginal group B streptococci colonization which does not require sophisticated 24-hour laboratory facilities. The method holds promise as a screening test for future intervention studies.

Bacteriological Techniques↗
PubMed1984

Early plasma protein and mineral changes after surgery: a two stage process.

Sequential changes in albumin, transferrin, alpha 1-acid glycoprotein, C reactive protein, fibrinogen, copper, iron, and zinc in plasma up to 24 h after hysterectomy were measured. No increases in the concentrations of the acute phase proteins alpha 1-acid glycoprotein, C reactive protein, and fibrinogen were observed until 6 h after the skin incision. These increases were preceded by significant falls at 2-4 h, and this was shown also by albumin, transferrin, iron, zinc, and copper. The ratios of iron and zinc to their binding proteins, transferrin and albumin, did not decrease until 4-6 h and their concentrations remained low for at least 24 h. These patterns suggest that at least two mechanisms operate after trauma. The early fall in the concentrations of the proteins in plasma is consistent with a prompt increase in microvascular permeability. The later decrease in binding of the metals iron and zinc to their transport proteins and the increase in concentrations of the acute phase proteins could be initiated by a common mediator.

Adult↗