No abstract

Quercetin is an effective inhibitor of human myeloperoxidase (MPO) activity, both with purified enzyme (IC50 = 3.5 microM) and in a system using stimulated human neutrophils. Quercetin is significantly more potent than three other related compounds (rutin, rutin sulfate and troxerutin) and than methimazole, a previously-known myeloperoxidase inhibitor. The inhibitory activity of quercetin is of the competitive type. Moreover, quercetin is directly able to scavenge hypochlorous acid (HOCl), a chlorinated species generated by the MPO/H2O2/Cl- system.

This work shows that the level of plasma tocopherol (vitamin E) which has free radical scavenging properties rises significantly during intensive exercise. It is proposed that mobilization of tocopherol could help to prevent lipoperoxidation phenomena occurring in exercising skeletal muscle. A hypothetical mechanism relating to a lipolysis effect is discussed to explain this mobilization.

Plasma thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured in 84 patients at risk of developing adult respiratory distress syndrome (ARDS) (44 patients following multiple trauma, 29 patients following abdominal surgery and 11 patients with acute pancreatitis). Forty-nine of these 84 patients developed an ARDS. High (greater than 140 pg/ml plasma) TXB2 values were found in 52/84 patients. The median values of TXB2 were: 360 pg/ml in multiple injured, 250 pg/ml in abdominal surgery and 410 pg/ml in acute pancreatitis patients. The median TXB2 value was 575 pg/ml in patients developing ARDS and 140 pg/ml in those without this complication: this difference was statistically significant (p less than 0.05). The median values of 6-keto-PGF1 alpha were 55 pg/ml in multiple injured, 25 pg/ml in abdominal surgery and 120 pg/ml in acute pancreatitis patients. The median 6-keto-PGF1 alpha value was 122 pg/ml in ARDS patients and 25 pg/ml in non-ARDS patients (statistically significant: p less than 0.05). High TXB2 and 6-keto-PGF1 alpha values were particularly related to sepsis in abdominal surgery patients (p less than 0.05) and in multiple injured patients (p less than 0.01). No relation could be established between abnormal TXB2 or 6-keto-PGF1 alpha values and death. High TXB2 values often persisted for several days and were observed particularly at the time ARDS diagnostic criteria were fulfilled.(ABSTRACT TRUNCATED AT 250 WORDS)

The intracellular distribution of thymidine phosphorylating kinases has been studied in rat liver at different times after partial hepatectomy. After conventional fractionation in 0.25 M sucrose, thymidine kinase is present in all fractions, the highest proportion being found, however, in the supernatant; phosphorylation of thymidine to TDP and TTP is detected only in the supernatant fraction from 24 h onwards after hepatectomy. Nuclei prepared in 2.2 M sucrose or in non-aqueous media have the same level of thymidine kinase activity and can never phosphorylate thymidine to TDP and TTP. I n the nuclear fractions, the absolute activity of thymidine kinase increases from 16 to 46 h after hepatectomy but represents a decreasing proportion of the activity of the liomogenate. At the same time, the proportion of kinase activity rises markedly in the supernatant fraction with a maximum of 83O/, in 40 h regenerating livers. The implications of these results are discussed.The activity of the thymidine-phosphorylating kinases is very low in resting tissues such as adult rat liver and increases markedly in proliferating tissues such as regenerating liver [1-3,7]. Changes in the intracellular distribution of thymidine-kinase during the mitoticyde have been considered as important control mechanisms in the rate of DNA synthesis [4]. The greatest proportion of these enzymes is found in the supernatant fraction after high speed centrifugation of aqueous homogenates [5-71. The possibility of loss of enzymes from the particulate fractions in aqueous media cannot be excluded: it has been shown, for instance, that deoxynucleoside phosphate esters are mainly in the nuclear fractions, when nuclei are prepared from lyophilized tissue in organic solvents [S, 91. I n the present work, the phosphorylation of dThd to TMP, TDP and TTP has been measured on subcellular fractions of regenerating liver, at different times after partial hepatectomy, before and during t,he DNA synthesis period. Because of the particular interest of the nuclear fractions in which phosphorylation reactions have been shown to occur [lo] made between the kinase activities of suspensions of nuclei isolated in aqueous and non-aqueous media. EXPERIMESTAL PROCEDURE Partial HepatectomyMale Wistar rats, weighing 180-200 g, were partially hepatectomized under ether anesthesia, according to the technique of Higgins and Anderson [12]. They were fasted 24 h before sacrifice and killed by decapitation a t different times after surgery. Tissue Fractionation by Differential CentrifugationFor each experiment 6-8 rats were used; they provided altogether approximately 12-I5 g regenerating liver. After sacrifice, the livers were quickly excised and perfused with ice-cold 0.25 M sucrose, then pooled and homogenized (2001, w/v) The pellets of the cytoplasmic fractions were washed twice by resuspending in 0.25 M sucrose with the aid of a glass bulb-homogenizer blown to fit the inside of the plastic centrifuge tubes, and resedimented with centrifugal forces identical with those us...