Gas-chromatographic resolution of the enantiomers of 3-(3,4-dihydroxyphenyl)alanine and its α-methyl analog

Methylation of (R,S)-DOPA with diazomethane gave the trimethyl derivative in which the phenolic hydroxy groups and the carboxy group were methylated. N-Methylated side products were also formed. N-Acylation of the racemic trimethyl derivative with (S)-α-methoxy-α-trifluoromethylphenylacetyl chloride gave two diastereomeric amides which were resolved by gas chromatography, the diastereomer derived from (S)-(−)-DOPA cluting first. The procedure was also applied to α-methyl-DOPA.     

A note on the structure of system state spaces and its implications on the existence of non-repeatable experiments

The implication of state space structure on the existence of a repeatable experimentE designed to determine if a states∈L has propertyP or notP is investigated. It is shown that if a state spaceL is connected, then no experimentE is repeatable. This formalism is used to demonstrate that if a propertyP has an associated set of points inL which is dense with dense complement inL, then there exists no repeatable experimentE which can be used to test whethers has propertyP or notP. Other consequences of this formalization are discussed.     

Wound complications after median sternotomy: A study of 61 patients from a consecutive series of 9,279

Among a consecutive series of 9,279 sternotomies performed during a period of 2(1/2) years, 61 (0.66%) patients developed significant wound complications. Of these, 58 (95.1%) survived. Sternal infection occurred in 36 patients (0.39%). Predisposing factors included chronic obstructive pulmonary disease, diabetes mellitus, obesity, closed chest massage, prolonged assisted ventilation, and excessive bleeding after operation. Positive end expiratory pressure (PEEP) did not, in itself, predispose to sternal dehiscence. Intermittent positive pressure breathing (IPPB) treatments caused excessive coughing, which may have increased the likelihood of dehiscence. Disposable drapes and expeditious surgery probably contributed to the low incidence of wound infection. Early diagnosis, surgical debridement, rewiring and primary closure with substernal drainage, without continuous antibiotic irrigation, resulted in satisfactory resolution in most patients.     

Ionescu-Shiley pericardial xenograft valve: Hemodynamic evaluation and early clinical follow-up of 326 patients

Dissatisfaction with the hemodynamic characteristics of available porcine valves prompted a clinical trial of the Ionescu-Shiley percardial xenograft (ISPX) valve. Three hundred fifty-six ISPX valves were implanted consecutively in 326 patients. Operative mortality was 2.6% (2/75) for aortic valve replacement alone and 7.7% (12/155) for aortic valve replacements that included reoperations and combined procedures such as mitral commissurotomy, annuloplasty, and coronary artery bypass. Operative mortality for all patients who underwent mitral valve replacement was 9.5% (14/147). The mean peak systolic gradient pressure in the aortic position was 5.4 mm Hg overall and 4.27 mm Hg with the size 19 mm valve. There were no embolic episodes in patients who received the ISPX valve in the aortic position. The available data indicate that the rate of peripheral embolism with the ISPX valve compares favorably with that of porcine valves. Considering its hemodynamic advantage, if the longterm durability of the full-orifice Ionescu-Shiley pericardial xenograft valve continues to be confirmed by follow-up studies, it is our opinion that it is the biologic valve of choice.     

Role of calcium ions in the regulation of intramitochondrial metabolism. Effects of Na+, Mg2+ and ruthenium red on the Ca2+-stimulated oxidation of oxoglutarate and on pyruvate dehydrogenase activity in intact rat heart mitochondria.

1. In uncoupled rat heart mitochondria, the kinetic parameters for oxoglutarate oxidation were very close to those found for oxoglutarate dehydrogenase activity in extracts of the mitochondria. In particular, Ca2+ greatly diminished the Km for oxoglutarate and the k0.5 value (concentration required for half-maximal effect) for this effect of Ca2+ was close to 1 microM. 2. In coupled rat heart mitochondria incubated with ADP, increases in the extramitochondrial concentration of Ca2+ greatly stimulated oxoglutarate oxidation at low concentrations of oxoglutarate, but not at saturating concentrations of oxoglutarate. The k0.5 value for the activation by extramitochondrial Ca2+ was about 20 nM. In the presence of either Mg2+ or Na+ this value was increased to about 90 nM, and in the presence of both to about 325 nM. 3. In coupled rat heart mitochondria incubated without ADP, increases in the extramitochondrial concentration of Ca2+ resulted in increases in the proportion of pyruvate dehydrogenase in its active non-phosphorylated form. The sensitivity to Ca2+ closely matched that found to affect oxoglutarate oxidation, and Mg2+ and Na+ gave similar effects. 4. Studies of others have indicated that the distribution of Ca2+ across the inner membrane of heart mitochondria is determined by a Ca2+-transporting system which is composed of a separate uptake component (inhibited by Mg2+ and Ruthenium Red) and an efflux component (stimulated by Na+). The present studies are entirely consistent with this view. They also indicate that the intramitochondrial concentration of Ca2+ within heart cells is probably about 2--3 times that in the cytoplasm, and thus the regulation of these intramitochondrial enzymes by Ca2+ is of likely physiological significance. It is suggested that the Ca2+-transporting system in heart mitochondria may be primarily concerned with the regulation of mitochondrial Ca2+ rather than cytoplasmic Ca2+; the possible role of Ca2+ as a mediator of the effects of hormones and neurotransmitters on mammalian mitochondrial oxidative metabolism is discussed.     

The activation of pyruvate dehydrogenase in the perfused rat heart by adrenaline and other inotropic agents.

Adrenaline resulted in a reversible 4-fold increase in the amount of pyruvate dehydrogenase in its active non-phosphorylated form in the perfused rat heart within 1 min. The increase was less in extent in hearts from starved or diabetic rats or in hearts from control rats oxidizing acetate, unless pyruvate was added to the perfusion medium. Increases could also be induced by other inotropic agents, supporting the hypothesis that increases in cytoplasmic Ca2+ can be relayed into mitochondria and influence oxidative metabolism.     

Stimulation of hepatic lipogenesis and acetyl-coenzyme A carboxylase by vasopressin.

The effect of vasopressin on the short-term regulation of fatty acid synthesis was studied in isolated hepatocytes from rats fed ad libitum. Vasopressin stimulates fatty acid synthesis by 30-110%. This increase is comparable with that obtained with insulin. Angiotensin also stimulates fatty acid synthesis, whereas phenylephrine does not. The dose-response curve for vasopressin-stimulated lipogenesis is similar to the dose-response curve for glycogenolysis and release of lactate plus pyruvate. Vasopression also stimulates acetyl-CoA carboxylase activity in a dose-dependent manner. Vasopressin does not relieve glucagon-inhibited lipogenesis, whereas insulin does. The action of vasopressin on hepatic lipogenesis is decreased, but not suppressed, in Ca2+-depleted hepatocytes. The results suggest that vasopressin acts on lipogenesis by increasing availability of lipogenic substrate (lactate + pyruvate) and by activating acetyl-CoA carboxylase.