Decidualization and insulin-like growth factor (IGF) binding protein: implications for its role in stromal cell differentiation and the decidual cell in haemochorial placentation

The somatomedins or insulin-like growth factors (IGFs) are polypeptides which are involved in proliferation of a number of cell types and have been implicated in fetal growth and development. Cellular responses to IGFs are mediated via binding to two classes of trans-membrane receptors. However, IGFs also bind with high affinity to binding proteins (IGF-BP) in plasma and other body fluids. In plasma the majority of IGF is associated with a GH-dependent 150 kd IGF-BP whereas a second small mol. wt (29-35 kd) IGF-BP is relatively unsaturated. It is this latter class of IGF-BP which has been demonstrated to be synthesized or secreted by a number of cell types and is detected in body fluids and secretions such as amniotic fluid, cerebrospinal fluid and milk. Although the exact relationship between these binding proteins and their role in IGF action has not been clarified, evidence suggests that the 29-35 kd form may function as an inhibitor and promoter of IGF action. During the menstrual cycle IGF-BP synthesis of this latter class appears associated with stromal fibroblast populations and it is proposed that this is involved in specifying proliferation of this cell type which differentiates into decidual cells. This IGF-BP also represents the major soluble secretory protein of the decidualized endometrium and its component decidual cell, during pregnancy and probably is the major source of the protein in pregnancy, contributing to the amniotic fluid and peripheral serum levels. In this article the implications of local decidual production of IGF-BP is discussed with reference to the thesis that decidualization, which is associated with species exhibiting haemochorial placentation, is involved in regulatory mechanisms of feto-placental development and growth.     

Effects of insulin infusion on human skeletal muscle pyruvate dehydrogenase, phosphofructokinase, and glycogen synthase. Evidence for their role in oxidative and nonoxidative glucose metabolism.

To determine whether activation by insulin of glycogen synthase (GS), phosphofructokinase (PFK), or pyruvate dehydrogenase (PDH) in skeletal muscle regulates intracellular glucose metabolism, subjects were studied basally and during euglycemic insulin infusions of 12, 30, and 240 mU/m2 X min. Glucose disposal, oxidative and nonoxidative glucose metabolism were determined. GS, PFK, and PDH were assayed in skeletal muscle under each condition. Glucose disposal rates were 2.37 +/- 0.11, 3.15 +/- 0.19, 6.71 +/- 0.44, and 11.7 +/- 1.73 mg/kg X min; glucose oxidation rates were 1.96 +/- 0.18, 2.81 +/- 0.28, 4.43 +/- 0.32, and 5.22 +/- 0.52. Nonoxidative glucose metabolism was 0.39 +/- 0.13, 0.34 +/- 0.26, 2.28 +/- 0.40, and 6.52 +/- 1.21 mg/kg X min. Both the proportion of active GS and the proportion of active PDH were increased by hyperinsulinemia. PFK activity was unaffected. Activation of GS was correlated with nonoxidative glucose metabolism, while activation of PDH was correlated with glucose oxidation. Sensitivity to insulin of GS was similar to that of nonoxidative glucose metabolism, while the sensitivity to insulin of PDH was similar to that of glucose oxidation. Therefore, the activation of these enzymes in muscle may regulate nonoxidative and oxidative glucose metabolism.     

Differential effects of mepacrine, chloroquine and hydroxychloroquine on superoxide anion generation, phospholipid methylation and arachidonic acid release by human blood monocytes

The 4-aminoquinolines chloroquine (CQ) and hydroxychloroquine (HCQ), and previously the 9-aminoacridine mepacrine (quinacrine) (MP), have been widely used in the treatment of inflammatory disorders such as rheumatoid arthritis and systemic lupus erythematosus. Their effects are believed to be mediated through phagocytic cells but the precise biochemical basis remains uncertain. We have investigated the effects of these drugs on monocyte superoxide anion (SO) generation elicited by 5 different stimuli-opsonised zymosan (STZ), FMLP, A23187, TPA and fluoride--and sought correlations with effects on two processes which have been linked with monocyte activation, namely arachidonate (AA) release and transmethylation of phosphatidyl ethanolamine (PE) to phosphatidylcholine (PC). In all experiments conditions were adjusted to achieve leucocyte concentrations of drug comparable to those found during in vivo therapy. Neither CQ nor HCQ had any marked effect on SO release induced by TPA, A23187 or fluoride ion, excluding a significant effect on protein kinase C (PKC), calmodulin-dependent kinase(s) or the membrane-bound, superoxide generating NADP(H) oxidase. In contrast MP inhibited the response to TPA and A23187. Each drug also had different effects on surface receptor-dependent responses; thus HCQ inhibited FMLP- but not STZ-induced SO release, whereas CQ and MP inhibited the response to both stimuli. Each drug also displayed different effects on AA release and phospholipid (PL)-methylation; MP and HCQ, but not CQ, inhibited STZ-stimulated AA release while MP and CQ but not HCQ inhibited basal rates of PL-methylation in mononuclear cells (MNC). However, only MP inhibited PL-methylation in an enriched monocyte population. We conclude that despite their close structural similarity, MP, CQ and HCQ each have different metabolic effects and their actions cannot simply be attributed to inhibition of lysosomal functions. Other possible mechanisms of action are discussed. The selective effects of each drug also provide further evidence for multiple pathways of monocyte activation.     

Arachnoid cysts of the posterior fossa

Arachnoid cysts of the posterior fossa are an uncommon clinical entity. The two cases presented in this review were evaluated without vertebral angiography. We think that the development of magnetic resonance imaging may obviate the need for angiography in selected cases.     

1H NMR studies of urine during fasting: excretion of ketone bodies and acetylcarnitine

High-resolution 1H NMR spectroscopy has been applied to a study of urine from five normal human subjects during a 48-h period of fasting and for 22 h thereafter. The excretion rates of all three ketone bodies (acetoacetate, 3-D-hydroxybutyrate, and acetone), acetylcarnitine, creatinine, and sarcosine during this period were measured. Parallel increases in the excretion of the ketone bodies and acetylcarnitine were observed during fasting with little change in the output of creatinine and sarcosine.