Plasma L-arginine concentration, oxygenation index, and systemic blood pressure in premature infants

OBJECTIVE: To determine the relationships between plasma L-arginine concentrations and the severity of respiratory distress syndrome (RDS) or systemic blood pressure in premature infants. DESIGN: Prospective, observational study. SETTING: Neonatal intensive care, tertiary referral hospital. SUBJECTS: Fifty-three premature infants. INTERVENTIONS: We measured arginine and nutritional intake, plasma arginine concentration, total amino acid concentrations, and blood pressure on days 3, 7, 14, and 21 of life. In 33 infants who received assisted ventilation, oxygenation index could be calculated to reflect the severity of RDS. The relationships between plasma arginine and oxygenation index or blood pressure were analyzed using multiple linear regression. MEASUREMENTS AND MAIN RESULTS: On day 3, plasma arginine concentrations were decreased compared with normal published values. Arginine concentrations increased with the day of life of measurement (p < .001) and with arginine intake (p < .001). After adjusting for arginine intake and day of life, an inverse relationship was found between oxygenation index and plasma arginine concentrations: (p = .025). No similar relationship was found between oxygenation index and the concentration of total amino acids. A weak positive relationship was found between plasma arginine concentration and systemic blood pressure. CONCLUSIONS: Increments in the oxygenation index, reflective of an increased severity of RDS, are associated with a decrease in plasma arginine concentration. This finding may reflect arginine consumption by the nitric oxide synthase pathway in the lungs of premature infants with RDS, or may be explained by increased arginine catabolism. The lack of a similar relationship between total plasma amino acids and oxygenation index supports the first interpretation.     

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Karyotypes were prepared from peripheral blood leukocytes in 77 couples in whom there was no apparent cause for recurrent spontaneous abortion. In addition to conventional staining, chromosomes were stained by the new technics for Q-, G-, or C-banding. Translocations were found in 5 of 154 persons (3.25% or 1:31 individuals). The frequency of translocations in the general adult population is 0.4% (1:255). Two translocations were apparent only with the new technics for banding. The incidence of chromosomal microanomalies was 7.79% (2.6% in the general population). Karyotyping of couples with recurrent abortion is recommended, with use of the new staining technics.     

Structure-activity relationships of four 11-hydroxyestrones isomeric at the C-9 and C-11 positions

The synthesis of 11 alpha-hydroxyestrone, 11 alpha-hydroxy-9 beta-estrone, and 11 beta-hydroxy-9 beta-estrone are presented. The reduction of 11-keto-9 beta-estrone 17-ethyleneketal by sodium in ethanol or sodium borohydride resulted in 11-hydroxy-9 beta-estrones. The 11-hydroxyl group configurations were opposite to expectations: sodium in boiling ethanol afforded the axial 11 beta-hydroxy-9 beta-estrone, while sodium borohydride in boiling tetrahydrofuran gave the equatorial 11 alpha-hydroxy-9 beta-estrone. In immature rat uterotropic bioassays using subcutaneous injections, 11 alpha-hydroxyestrone was 2 times as active as 11 alpha-hydroxy-9 beta-estrone, and 11 beta-hydroxyestrone was 10 times as active as 11 beta-hydroxy-9 beta-estrone.     

Further characterization of the complementation group B temperature-sensitive mutant of respiratory syncytial virus

ts-2, a temperature-sensitive and plaque morphology mutant of respiratory syncytial virus and sole representative of complementation group B, was compared with members of the other complementation groups of respiratory syncytial virus (group A [ts-1] and group C [ts-7]). ts-2 was found to be 10- to 1,000-fold more restricted in growth and ability to spread at restrictive temperatures (37, 38, and 39 degrees C) than at the permissive temperature (32 degrees C). In temperature shift-up experiments, the ts defect of ts-1 and other members of complementation group A was found to effect a late function that was required for at least 13 h in the replicative cycle. The ts lesion of ts-7 affected a function early in the replication cycle. In contrast, ts-2 was not temperature sensitive when studied by the shift-up technique. The discrepancy between the ts plaque property and failure to detect temperature sensitivity during the shift-up experiment was resolved when it was shown that ts-2 had a defect in adsorption or penetration or both at the restrictive temperature. Clonal analysis of revertant ts-2 showed a coordinate restoration of ts+ phenotype ans syncytium-forming capacity. It appears that ts-2 has a defect in a protein that is involved in adsorption and/or penetration of virus and is also responsible for cell fusion activity.     

Can phenformin-induced lactic acidosis be prevented?

Although patients taking phenformin are more likely to develop lactic acidosis in the presence of renal, cardiovascular, or hepatic disease, criteria for safe use of the drug are not well established. Eight diabetics died of lactic acidosis in Nottingham in 1972-5 and all were taking phenformin in therapeutic doses. Six had attended the diabetic clinic within a month of their terminal illness. Two patients had appreciable renal impairment and should not have been given phenformin. Four had hypertension and minimal evidence of renal disease, while in two no predisposing factor was identified. There are so many contraindications to the use of phenformin that it is doubtful whether patients on the drug can be monitored adequately. We suggest that phenformin should be withdrawn from general use.     

Inactivation of pyridoxal phosphate dependent enzymes by mono- and polyhaloalanines

beta,beta-Dichloro- and beta,beta,beta-trifluoroalanine irreversibly inactivate a number of pyridoxal phosphate dependent enzymes which catalyze beta- or gamma-elimination reactions. The inactivation is time dependent and the rate of inactivation is first order in enzyme concentration. This suggests that inactivation is due to covalent modification of the enzyme by a species generated at the active site from the polyhaloalanine (i.e., suicide inactivation). Monohaloalanines are substrates and do not inactivate. For gamma-cystathionase, covalent and stoichiometric attachment of [1-14C]beta,beta,beta-trifluoroalanine was shown. It is proposed that the mechanism of inactivation involves Schiff base formation between inactivator and enzyme-bound pyridoxal and subsequent elimination of HC1 from dichloroalanine or HF from trifluoroalanine. This results in the formation of a beta-halo-alpha,beta unsaturated imine, an activated Michael acceptor. Michael addition of a nucleophile at the active site leads to covalent labeling of the enzyme and inactivation. Alanine racemase is also inactivated by the two polyhaloalanines. Glutamate-pyruvate and gultamate-oxaloacetate transaminase are inactivated by monohaloalanines but not by polyhaloalanines.     

How long does chlorpromazine last?

An attempt has been made to relate the retarded adsoprtion to red cells of the slow reacting hemolytic phosphatide Rac. 1-octadecyl-2-benzyl-glycero-3-phosphorylcholine (benzyl-lysolecithin) to its aggregation status in aqueous solution. Light scattering measurements indicate a critical micelle concentration at 37 degrees of less than 2 X 10(-6) M. The micellar weight as determined by angle dependent light scattering is 6 X 10(7) with about 97 000 molecules per micells. The aggregates, which according to electron-microscopic observations are more similar to lecithin-liposomes than to usual lysolecithin-micelles, undergo a phase transition at 14 degrees from a tightly packed liquid-crystalline state to the more loose structure of a gel phase with increased mobility of the aliphatic chains. The enthalpy of transition is 4.2 kcal/mole. These changes of the micellar structure are reflected in the binding kinetics of benzyl-lysolecithin to red cells in that the binding rate is rather constant below, but strongly increasing above the transition temperature. It is concluded that the unusual micellar structure is responsible for the retarded adsorption of this lysolecithin analog to red cells and that the rate of adsorption is probably determined by the rate of escape of single lysophosphatide molecules from the micelles.     

Phospholipids and oxophospholipids in atherosclerotic plaques at different stages of plaque development

We identified and quantified the hydroperoxides, hydroxides, epoxides, isoprostanes, and core aldehydes of the major phospholipids as the main components of the oxophospholipids (a total of 5–25 pmol/μmol phosphatidylcholine) in a comparative study of human atheroma from selected stages of lesion development. The developmental stages examined included fatty streak, fibrous plaque, necrotic core, and calcified tissue. The lipid analyses were performed by normal-phase HPLC with on-line electrospray MS using conventional total lipid extracts. There was great variability in the proportions of the various oxidation products and a lack of a general trend. Specifically, the early oxidation products (hydroperoxides and epoxides) of the glycerophosphocholines were found at the advanced stages of the plaques in nearly the same relative abundance as the more advanced oxidation products (core aldehydes and acids). The anticipated linear accumulation of the more stable oxidation products with progressive development of the atherosclerotic plaque was not apparent. It is therefore suggested that lipid infiltration and/or local peroxidation is a continuous process characterized by the formation and destruction of both early and advanced products of lipid oxidation at all times. The process of lipid deposition appears to have been subject to both enzymatic and chemical modification of the normal tissue lipids. Clearly, the appearance of new and disproportionate old lipid species excludes randomness in any accumulation of oxidized LDL lipids in atheroma.