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Biomedical subjects

P Belfrage

Publications and source records attributed to P Belfrage.

At least 109 records · Page 6Linked to original sources

Characteristics of the lipolytic beta-adrenergic receptors in hamster adipocytes.

Hamster adipocyte beta-adrenergic receptors were characterized by the effect on the lipolysis rate of several selective beta-adrenergic agonists and antagonists. Prenalterol and procaterol, selective beta 1- and beta 2-agonists, respectively, both stimulated the lipolysis rate half-maximally at 1-2 microM, a concentration approximately 100-fold higher than that needed for half-maximal stimulation by isoprenaline. The maximal procaterol effect was similar to that of isoprenaline, while the effect of prenalterol was 40% lower. Submaximally isoprenaline-stimulated lipolysis was half-maximally inhibited by propranolol at 0.2 microM and by atenolol and H 35/25, selective beta 1- and beta 2-antagonists, at 23 and 6 microM concentration, respectively. Highly specific beta 1 and beta 2 stimulation was induced by incubation with prenalterol or procaterol, with simultaneous maximal selective beta 2 or beta 1 inhibition, respectively. The maximal beta 2 stimulation was approximately twice the corresponding beta 1 effect under these conditions, the sum of both effects closely approaching that of maximal nonselective beta-adrenergic stimulation with isoprenaline. Similar results were obtained with the selective beta 2-antagonist, ICI 118,551, or the beta 1-antagonists, pamatolol and practolol. The findings are most easily explained by the existence of a heterogeneous beta 1- and beta 2-adrenergic receptor population on hamster adipocytes.

Adipose Tissue↗

Direct evidence that cholesterol ester hydrolase from adrenal cortex is the same enzyme as hormone-sensitive lipase from adipose tissue.

Several properties of the cytosolic cholesterol ester hydrolase from bovine adrenal cortex were investigated and those properties were compared directly with those of the well-characterised hormone-sensitive lipase, the rate-limiting enzyme in adipose tissue lipolysis. Properties examined included: (a) activity against different substrates; (b) susceptibility to inhibition by NaF, Hg2+ ions and diisopropyl fluorophosphonate; (c) subunit molecular weight as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate; (d) ability to serve as a substrate for cyclic AMP-dependent protein kinase; (e) effect of phosphorylation on enzyme activity; and (f) degradation pattern of polypeptides following limited proteolysis. In all respects the two enzymes exhibited essentially identical characteristics. It is therefore concluded that the same protein, or two very similar proteins, catalyses the hydrolysis of cholesterol esters in adrenal cortex and lipolysis in adipose tissue. The implication of this finding is discussed in relation to the hormonal control of steroidogenesis in adrenal cortex and of lipolysis in adipose tissue.

Adipose Tissue↗

Fetal and maternal plasma catecholamine levels at elective cesarean section under general or epidural anesthesia versus vaginal delivery.

Fetal and maternal plasma levels of catecholamines were measured at birth in 40 women with normal term pregnancies who underwent elective cesarean section. Twenty women were operated on under general anesthesia, and 20 under epidural anesthesia. For comparison, the same measurements were also made in 10 women who underwent vaginal delivery without signs of intrapartum fetal distress. Maternal venous levels of catecholamines were elevated in all three groups as compared to values in the resting adult. The highest levels were found in the vaginal delivery group (norepinephrine and epinephrine, 3.9 +/- 2.1 and 1.1 +/- 1.0 nmoles/L, respectively), and the lowest in the epidural cesarean section group. Fetal outcomes were similar in all three groups, as judged by Apgar scores and by measurements of umbilical arterial blood gases. In spite of that, neonates delivered vaginally showed a markedly higher sympathoadrenal activation (norepinephrine and epinephrine, 31.8 +/- 24.1 and 5.1 +/- 7.6 nmoles/L, respectively) than those born by elective cesarean section. In the latter group, however, it was found that the type of maternal anesthesia influenced fetal sympathoadrenal activation, since neonatal levels of catecholamines were higher in the epidural section group (norepinephrine and epinephrine, 9.5 +/- 6.4 and 4.0 +/- 4.5 nmoles/L, respectively) than in the general anesthesia group (norepinephrine and epinephrine, 3.2 +/- 2.7 and 1.0 +/- 1.4 nmoles/L, respectively). These results may have a certain clinical relevance since fetal sympathoadrenal activation is thought to promote extrauterine adaptation.

Anesthesia, Epidural↗

Intracervical application of prostaglandin gel for induction of term labor.

A new gel for local application of prostaglandins has been elaborated. The new gel, based on a lyophilized prostaglandin E2 (PGE2) starch powder, seems to have solved most of the pharmaceutical and clinical problems associated with local administration of prostaglandins. In a randomized double-blind study, 50 nulliparous patients with an unfavorable cervical state at term were given 2 ml gel containing 0.5 mg PGE2 (PGE2 gel) or gel without PGE2 (placebo gel). The gel was deposited into the cervical canal. Among patients given PGE2 gel, 11 of 25 had induced labor, delivering without further stimulation within 24 hours. In patients given placebo gel, 2 of 25 were delivered with 24 hours. This difference is statistically significant (P less than .01). Patients undelivered after treatment with PGE2 gel achieved a considerable and statistically significant improvement of cervical score, whereas in patients in whom labor was not induced successfully by placebo gel treatment no significant changes in cervical score were registered. In a subsequent open study another 70 term patients of varied parity were given 0.5 mg PGE2 gel. Thirty-eight patients (54%) had successfully induced labor. Among the remaining undelivered patients, considerable ripening of the cervix occurred. Thus, the cervical score changed from a mean of 3.2 prior to treatment to a mean of 6.5 by 24 hours after treatment. Gastrointestinal discomforts were not observed. Signs of uterine hyperstimulation were registered in 1 patient.

Adolescent↗

Synthesis of 14C-labeled alkyl polyoxyethylene detergents.

Procedures for the synthesis and purification of two 14C-labeled alkyl polyoxyethylene detergent preparations are described. One of the preparations consisted mainly of [14C]dodecyloctaoxyethylene ether, the other consisted mainly of [14C] octylhexaoxyethylene ether, with critical micellar concentrations of approximately 50 microM and 10 mM, respectively. Condensation of alkyl bromides with fractionated polyethyleneglycol resulted in less polydisperse products than conventional ethylene oxide condensation. Highly purified detergent species could easily be obtained from the preparations by thin-layer chromatography. Their use as tracers greatly simplifies determination of detergent concentration during protein solubilization and fractionation.

Chemical Phenomena↗

Effects of insulin on lipolysis and lipogenesis in hamster white adipocytes with high sensitivity to hormones.

A modified procedure for preparation of hamster adipocytes by collagenase digestion under carefully controlled conditions has been developed. The adipocytes were 4- to 8-fold more sensitive to catecholamine stimulation of lipolysis than cells prepared by a commonly used method (Hittelman, K.J., Wu, C.F. and Butcher, R.W. (1973) Biochim. Biophys. Acta 304, 188-196) and also more sensitive to the anti-lipolytic action of insulin. The effects of insulin on lipogenesis, measured as [3H]glucose conversion to cell lipids, and on catecholamine-stimulated lipolysis were compared under identical conditions with the same cell batch. Isoprenaline-stimulated lipolysis was found to be half-maximally inhibited by an insulin concentration 8-fold lower than that stimulating lipogenesis to a corresponding extent (half-maximal effects at insulin concentrations of 40 vs. 300 pM). A similar difference was found when cells had been stimulated with adrenaline instead of isoprenaline.

Adipose Tissue↗

Neonatal depression after obstetrical analgesia with pethidine. The role of the injection-delivery time interval and of the plasma concentrations of pethidine and norpethidine.

Pethidine (100 mg) was administered i.m. to women in labor at different times before delivery. The interval before respiration in the newborn became sustained was shorter if pethidine was given less than one hour before delivery. The respiratory rate of the newborn increased after naloxone injection in 40 per cent of the cases, mostly when intrauterine exposure to pethidine exceeded one hour. The plasma concentrations of pethidine and norpethidine were measured in mother and newborn. The concentrations in the umbilical vein and artery indicted a continuous net transfer of pethidine from mother to fetus for approximately two hours. This correlated with the clinical finding of maximal neonatal depression 2-3 hours after maternal injection. The concentrations of norpethidine increased with a longer time interval between injection and delivery, but were probably too low to have any effect on the newborn. Neonatal depression seems to be related to the amount of unmetabolized pethidine that has been transferred from mother to fetus but not to norpethidine as had been suspected earlier.

Anesthesia, Obstetrical↗

Regulation of adipose-tissue lipolysis by phosphorylation of hormone-sensitive lipase.

Hormone-sensitive lipase has been purified from rat adipose tissue to almost 50 per cent protein purity and partially characterized. The isolated enzyme can be phosphorylated by ATP-Mg2+ in the presence of the catalytic subunit of cyclic AMP-dependent protein kinase from the same tissue. Its activity towards emulsified triglyceride is thereby increased two-fold. The enzyme is phosphorylated also in the intact adipocyte, verifying the physiological relevance of the findings with the isolated enzyme. Noradrenaline causes a rapid increase in phosphorylation of the enzyme in intact adipocytes, immediately followed by a marked increase of its activity. Addition of dibutyryl-cyclic AMP to the adipocytes causes the same effects. The extent of phosphorylation of the enzyme after maximal noradrenaline stimulation of the adipocytes is rapidly decreased by insulin addition in close association with inhibition of the lipase activity. The results demonstrate that these hormones regulate the activity of the hormone-sensitive lipase, ie the rate of lipolysis in the adipocytes, by changes of the degree of phosphorylation of the enzyme.

Adenosine Triphosphate↗

Micromethods for analysis of lipids in endomyocardial biopsy specimens.

Triglycerides and phospholipids extracted from endomyocardial biopsy specimens were quantitated with sensitive photometric methods and the fatty acid composition of phospholipids was determined after separation of the methyl esters by gas chromatography. The degree of triglyceride accumulation was expressed as the molar ratio triglyceride/phospholipid since in most cases the phospholipid concentration is relatively constant. The representativity of the analysis of endomyocardial biopsy was investigated by comparing lipid analyses of large and small myocardial specimens obtained at necropsy. The methods described may be valuable tools in studies on metabolic disturbances in different cardiomyophaties.

Biopsy↗