Generation and intermolecular reactions of 2-indolylacyl radicals.

The generation of 2-indolylacyl radicals from the corresponding phenyl selenoesters, aldehydes, and alpha-keto carboxylic acids and the scope of their participation in intermolecular addition reactions to carbon-carbon double bonds have been studied. Whereas the phenyl selenoester method has provided easy access to a variety of 1,4-dicarbonyl compounds bearing the 2-acylindole moiety, the glyoxylic acid route has been employed for the preparation of 2-indolyl pyridyl ketones.

Synthesis and biological evaluation of 1,3,4-triaryl-3-pyrrolin-2-ones, a new class of selective cyclooxygenase-2 inhibitors.

The synthesis and structure activity relationships (SAR) of a series of novel selective COX-2 inhibitors are reported. The results show that some of the 1,3,4-triaryl-3-pyrrolin-2-ones 1 are more potent as COX-2 inhibitors than celecoxib, and that lactam Id has the same selectivity.

Synthesis and dopaminergic activity of heterocyclic analogues of 5,6-dihydroxy-2-aminotetralins.

The heterocyclic analogues of 5,6-dihydroxy-2-aminotetralins (6) were synthesized and their in vitro dopaminergic activity was compared to that of (-)-DP-5,6-ADTN and the novel potent agonist Z12571. The results show that changing the cathecol ring for a heterocycle decreases the D1-like activity of the target molecules 6. However, the D2-like activity of tetrahydroquinoline (6j) was comparable to that of (-)-DP-5,6-ADTN.

Synthesis of water-soluble phenytoin prodrugs.

The synthesis of novel water-soluble phenytoin derivatives, bearing an ionizable group, and a preliminary study for in vitro blood hydrolysis are reported. The results show that hydrolysis of amino esters 8 is very fast, much more than that of fosphenytoin.

Live transmission of neonatal echocardiograms from underserved areas: accuracy, patient care, and cost.

OBJECTIVE: Echocardiography is an important tool in the diagnosis and management of critically ill neonates. The authors hypothesized that live telemedicine guidance and interpretation of neonatal echocardiograms from underserved areas would improve management, prevent unnecessary transports, enhance sonographer proficiency, and result in monetary savings. MATERIALS AND METHODS: Using personal computers capable of real-time transmission of echocardiograms over three integrated services digital network (ISDN) telephone lines, pediatric cardiologists interpreted echocardiograms, suggested views to sonographers, and made recommendations to neonatologists 200 miles away. Analyses of accuracy, management, echocardiogram quality, time, and costs were carried out prospectively. RESULTS: Sixty studies were transmitted over 7 months. Indications for echocardiography were suspected congenital heart disease (n = 29), suspected patent ductus arteriosus (PDA) (n = 27), and hemodynamic instability (n = 4). Diagnoses were critical congenital heart disease (n = 4), noncritical heart disease (n = 8), PDA (n = 21), ventricular dysfunction (n = 5), persistent pulmonary hypertension (n = 3), and normal (n = 19). Videotape review confirmed all telemedicine interpretations. The echocardiogram led to immediate change in management in 25 cases (42%), and echocardiogram quality was improved in 53 studies (88%). Time from request to completion of echocardiography was 43+/-30 min. Monetary savings from five avoided transports exceeded all expenses. CONCLUSION: Live transmission of neonatal echocardiograms over three ISDN lines is diagnostic, improves patient care and echocardiography quality, and is cost effective.

Molecular modeling of (E)-1-alkyl-4(3)-[2-(1H-azolyl)vinyl]-pyridinium salts and evaluation of their behavior towards choline acetyltransferase.

A new type of extended pi-system aza-analogue of (E)-4-[2-(1-naphthylvinyl)]-1-substituted pyridinium salts (NVP+) has been designed and its inhibitory activity towards choline acetyltransferase (ChAT) has been evaluated in vitro. Among the several examples of the title quaternary salts synthesized 2 and 3, the indolylvinylpyridinium salt 2e is the only one to show a very low ChAT inhibition. The molecular modeling study is highly illustrative of their behavior towards ChAT and interaction with the recognition site. Thus, several selected cations together with the reference NVP+ compound 1a were studied at the PM3 and AM1 levels respectively. At the global minima, all the compounds are planar, which, from the electron charge distribution, shows a degree of polarization similar to the NVP+ model compound 1a. However, the fitting of all optimized structures indicated that only the indole derivative 2e showed the same aromatic fragment orientation as 1a, which allows us to define a volume that is not accessible to ligands in the enzyme and consequently to a refined model of the choline acetyltransferase recognition site.

L-type calcium current in pediatric and adult human atrial myocytes: evidence for developmental changes in channel inactivation.

Animal studies have documented the presence of marked, species-dependent, developmental changes in the properties of the L-type calcium current in cardiac myocytes. In an effort to understand the postnatal changes which occur in the calcium current in human heart, we characterized the calcium current in atrial myocytes isolated from 17 pediatric and older children (ages 3 d to 14 y) and 12 adult (ages 43-79 y) human hearts using the whole-cell patch clamp technique. In contrast to animal models, we found no evidence for age-related changes in calcium current density, steady-state inactivation, or kinetics of recovery from inactivation, suggesting that, in human atrium, calcium channels are in many aspects functionally mature at the time of birth. However, statistically significant differences were found in the kinetics of calcium current inactivation, with calcium current measured in cells isolated from pediatric human atria inactivating approximately 2-fold faster than cells isolated from adult hearts. These results suggest a possible role for age-related changes in calcium current inactivation in the shortened action potential duration observed in pediatric compared with adult human atrium.