A novel small-molecule enantiomeric analogue of traditional (-)-morphinans has specific TLR9 antagonist properties and reduces sterile inflammation-induced organ damage.

TLR9 is a key determinant of the innate immune responses in both infectious and sterile injury. Specific antagonism of TLR9 is of great clinical interest to reduce tissue damage in a wide range of pathologies, and has been approached by modification of nucleic acids, the recognized ligand for TLR9. Such oligonucleotide-derived pharmacotherapeutics have limitations in specificity for nucleic acid receptors, significant potential for immunologic recognition with generation of innate and adaptive immune responses, and limited bioavailability.

Exogenous fluorescent tracer agents based on pegylated pyrazine dyes for real-time point-of-care measurement of glomerular filtration rate.

Novel pyrazine carboxamides bearing hydrophilic poly(ethylene glycol) (PEG) moieties were designed, synthesized, and evaluated for use as fluorescent glomerular filtration rate (GFR) tracer agents. Among these, compounds 4d and 5c that contain about 48 ethylene oxide units in the PEG chain exhibited the most favorable physicochemical and renal clearance properties. In vitro studies show that these two compounds have low plasma protein binding, a necessary condition for renal excretion.

Hydrophilic pyrazine dyes as exogenous fluorescent tracer agents for real-time point-of-care measurement of glomerular filtration rate.

Various hydrophilic pyrazine-bis(carboxamides) derived from 3,5-diamino-pyrazine-2,5-dicarboxylic acid bearing neutral and anionic groups were prepared and evaluated for use as fluorescent glomerular filtration rate (GFR) tracer agents. Among these, the dianionic d-serine pyrazine derivatives 2d and 2j, and the neutral dihydroxypropyl 2h, exhibited favorable physicochemical and clearance properties. In vitro studies show that 2d, 2h, and 2j have low plasma protein binding, a necessary condition for renal excretion.

Fluorescence-enhanced europium-diethylenetriaminepentaacetic (DTPA)-monoamide complexes for the assessment of renal function.

Real-time, noninvasive assessment of glomerular filtration rate (GFR) is essential not only for monitoring critically ill patients at the bedside, but also for staging and monitoring patients with chronic kidney disease. In our pursuit to develop exogenous luminescent probes for dynamic optical monitoring of GFR, we have prepared and evaluated Eu(3+) complexes of several diethylenetriamine pentaacetate (DTPA)-monoamide ligands bearing molecular "antennae" to enhance metal fluorescence via intramolecular ligand-metal fluorescence resonance energy transfer process. The results show that Eu-DTPA-monoamide complex 18b, which contains a quinoxanlinyl antenna, exhibits large (ca.

Detection of individual microbubbles of ultrasound contrast agents: imaging of free-floating and targeted bubbles.

Rationale And Objectives: During echo examinations with microbubble contrast, individual "dots" of ultrasound reflection can be visualized. To address the question whether these signals represent individual microbubbles, very dilute suspensions of ultrasound contrast agents or individual microbubbles attached to Petri dishes were prepared and studied by ultrasound imaging.

Methods: Microbubble suspensions were diluted in saline and evaluated by a clinical ultrasound imaging system.

Albumin-binding MR blood pool agents as MRI contrast agents in an intracranial mouse glioma model.

Intravenous MRI contrast agents are commonly used to improve the detection of intracranial tumors and other central nervous system (CNS) lesions for diagnosis and treatment planning. Two small-molecule, albumin-binding blood pool contrast agents (MP-2269 and MS-325) of potential clinical significance were evaluated at 1.5 Tesla in a mouse glioma model and compared with an extracellular contrast agent (OptiMARK).

Microbubbles induce renal hemorrhage when exposed to diagnostic ultrasound in anesthetized rats.

The generation of ultrasound (US) bioeffects using a clinical imaging system is controversial. We tested the hypothesis that the presence of microbubbles in the US field of a medical imager induces biologic effects. Both kidneys of anesthetized rats were insonified for 5 min using a medical imaging system after the administration of microbubbles.