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[Basic therapy of chronic heart failure with digitalis or diuretics?].

Sixteen patients in heart failure and sinus rhythm were, after a four-week treatment-free period, randomly assigned to receive, for four to six weeks, either a diuretic combination (hydrochlorothiazide + triamterene) or a digitalis glycoside. Subsequently the treatment was exchanged between the two groups. Without treatment nine patients were in stage II (New York Heart Association classification), seven in stage III. Pulmonary wedge pressure at rest was 27 +/- 14, on exercise 32 +/- 8 mm Hg, cardiac output 5.3 +/- 1.0 at rest and 7.8 +/- 2.3 l/min on exercise. Digitalis glycosides improved symptoms by one stage in three of 16 patients. All objective measures showed slight but not significant improvement. Diuretic treatment improved symptoms in five patients, while heart size and echocardiographically measured ventricular volume decreased slightly. Cardiac output decreased at rest, but not significantly, and on exercise not at all. Pulmonary arterial pressure (21 +/- 9 mm Hg), pulmonary wedge pressure (13 +/- 7 mm Hg) and pulmonary artery pressure on exercise (39 +/- 11 mm Hg) were significantly lower on diuretics than without treatment. The results support the primary use of diuretics in the treatment of chronic heart failure.

Aged↗

Desymmetrization of enone-diones via rhodium-catalyzed diastereo- and enantioselective tandem conjugate addition-aldol cyclization.

Catalytic tandem conjugate addition-enolate trapping represents an effective strategy for the design of catalytic transformations that enable formation of multiple C-C bonds. Recently, using enantioselective rhodium-catalyzed conjugate addition methodology, we developed a catalytic tandem conjugate addition-aldol cyclization of keto-enones. Here, we report related desymmetrizations and parallel kinetic resolutions involving the use of diones as terminal electrophiles. The Rh-enolate generated on enone carbometallation effectively discriminates among four diastereotopic pi-faces of the appendant dione, ultimately providing products that embody four contiguous stereocenters, including two adjacent quaternary centers, with quantitative diastereoselection and high levels of enantiomeric excess. This methodology allows concise entry to optically enriched seco-B ring steroids possessing a 14-hydroxy cis-fused C-D ring junction, as found in naturally occurring cardiotonic steroids derived from digitalis.

Aldehydes↗

Proximity relationships in rhodopsin.

Energy transfer was used as a spectroscopic ruler to deduce proximity relationships within bovine rhodopsin in digitonin solution. Rhodopsin was specifically labeled with fluorescent chromophores at three sites. Site A was alkylated by fluorescent derivatives of iodoacetamide. Site B was labeled by fluorescent disulfides, by a disulfide-sulfhydryl interchange reaction. Sites A and B are sulfhydryl residues. Acridine derivatives were tightly bound to site C by noncovalent interactions. The labeled rhodopsins retained their 500-nm absorption band and were regenerable after bleaching, suggesting that the fluorescent probes did not grossly perturb the conformation of the protein. A fluorescent chromophore at one of these sites served as the energy donor, while 11-cis retinal was the energy acceptor. The efficiency of singlet-singlet energy transfer was determined from the quantum yield and excited-state lifetime of the donor in the presence and absence of the acceptor. By Förster's theory, the apparent distances between 11-cis retinal and sites A, B, and C were calculated to be 75,55, and 48 A, respectively. Energy transfer measurements on rhodopsin labeled at two of these sites gave these apparent distances: 35 A for A to B, 32 A for A to C, and 30 A for B to C. These energy transfer studies suggest that the rhodopsin molecule has a length of at least 75 A. Thus, the rhodopsin molecule appears to be sufficiently long to traverse the disc membrane. Rhodopsin might act as a light-controlled gate.

Acridines↗

Ouabain-binding-site photoaffinity probes that label both subunits of Na+,K+-ATPase.

4"'-Diazomalonyldigitoxin and its isomer, 3"'-diazomalonyldigitoxin, have been synthesized at high specific radioactivity and used as photolabels for the Na,K-ATPase (ATP phosphohydrolase, EC 3.6.1.3) purified from Electrophorus electricus. Photoaffinity labeling experiments using both type I and type II complexes of enzyme with both photolabels showed ouabain-protectable labeling of the alpha as well as the beta subunit. These data suggest that, in the purified eel enzyme, the alpha and beta subunits are in intimate contact, at least in the region of the third digitoxose of the "sugar-specific" binding site.

Affinity Labels↗