C-peptide, IGF-I, sex-steroid hormones and adiposity: a cross-sectional study in healthy women within the European Prospective Investigation into Cancer and Nutrition (EPIC)

Objectives: The risk of some cancers is positively associated with body weight, which may influence circulating levels of sex-steroid hormones, insulin and IGF-I. Interrelationships between these hormones and the associations with adiposity were evaluated in healthy women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods: A cross-sectional analysis was performed on anthropometric and hormonal data from 743 pre- and 1217 postmenopausal women. Body mass index (BMI) and waist circumference were used as indicators of adiposity. C-peptide, Insulin Growth Factor (IGF)-I, Insulin Growth Factor binding protein (IGFBP)-3, androgens, estrogens and sex hormone binding globulin (SHBG) were measured by immunoassays; free sex steroid concentrations were calculated.Results: BMI and waist circumference were positively correlated with estrogens in postmenopausal women and with C-peptide, free testosterone and inversely with SHBG in all women. C-peptide and IGF-I were inversely correlated with SHBG, and positively with free sex steroids in postmenopausal women. IGF-I was positively associated with postmenopausal estrogens and androgen concentrations in all women.Conclusions: Sex-steroid concentrations appear to be regulated along several axes. Adiposity correlated directly with estrogens in postmenopausal women and with insulin, resulting in lower SHBG and increased levels of free sex steroids. Independent of adiposity and insulin, IGF-I was associated with decreased SHBG levels, and increased concentrations of androgens and postmenopausal estrogens.     

A network of investigator networks in human genome epidemiology

The task of identifying genetic determinants for complex, multigenetic diseases is hampered by small studies, publication and reporting biases, and lack of common standards worldwide. The authors propose the creation of a network of networks that include groups of investigators collecting data for human genome epidemiology research. Twenty-three networks of investigators addressing specific diseases or research topics and representing several hundreds of teams have already joined this initiative. For each field, the authors are currently creating a core registry of teams already participating in the respective network. A wider international registry will include all other teams also working in the same field. Independent investigators are invited to join the registries and existing networks and to join forces in creating additional ones as needed. The network of networks aims to register these networks, teams, and investigators; be a resource for information about or connections to the many networks; offer methodological support; promote sound design and standardization of analytical practices; generate inclusive overviews of fields at large; facilitate rapid confirmation of findings; and avoid duplication of effort.     

Homocysteinemia is inversely correlated with platelet count and directly correlated with sE- and sP-selectin levels in females homozygous for C677T methylenetetrahydrofolate reductase

Plasma homocysteine levels depend in part on the molecular nature of the methylenetetrahydrofolate reductase (MTHFR) and on blood folate intake. Little has been reported on platelet counts in the presence of hyperhomocysteinemia and MTHFR polymorphisms, with the exception of delayed platelet recovery in homozygous MTHFR C677T subjects after treatment with methotrexate for ovarian cancer. The aim of this investigation was to evaluate the possibility of a link between the platelet count and plasma homocysteine levels in different MTHFR variants in 165 female patients. Determinations of plasma homocysteine levels were by ELISA and of MTHFR polymorphisms (A1298C and C677T) were by inverse hybridization. Serum P- and E-selectin concentrations were obtained by ELISA. An inverse correlation (R=-0.88, P<0.001) was observed between blood platelet counts and plasma homocysteine levels in the women homozygous for MTHFR C677T. This correlation did not depend on pregnancy or other variables reported. Serum concentrations of sE- and sP-selectin, markers of endothelial and platelet activation, were significantly and positively correlated with homocysteine levels. These findings suggest that homocysteine affects platelet numbers in women with MTHFR C677T possibly consequent to endothelial and platelet activation.     

Striated muscle cells in the thymus of reptiles and birds: An electron microscopic study

Striated muscle cells, the “myoid cells” of light microscopic literature, are consistently found in the thymus of reptiles and birds. Round or elongated myoid cells resemble adult skeletal or cardiac muscle fibers; however, the location of the nucleus, the course of the myofibrils, the arrangement and proportion of the thick and thin filaments, and the morphology and topography of the membranous components of the sarcoplasm are variable. Other myoid cells which contain either primitive myofibrils, irregular bundles of myofilaments associated with primitive Z plaques, or thick and thin filaments alone scattered throughout the cytoplasm, recall the various stages of the development of skeletal and cardiac muscle fibers. In these cells the ribosomes are often, but not always abundant and appear in places arranged in helices and rosettes. It is suggested that a postnatal myogenesis takes place in the thymus. Anomalous muscle cells contain thin filaments almost exclusively. In some of these cells, thin filaments are arranged in I-segments that appear either independent of each other or interdigitated in pseudosarcomeres. Finally, some myoid cells appear to have degenerated. Desmosomes join myoid cells to reticular cells, to other myoid cells, and to epithelial cells in the walls of intraparenchymal cysts. The origin of the myoid cells from reticular cells is suggested.     

Immunological patterns identifying disease course and evolution in multiple sclerosis patients

Reliable, and easy to measure, immunological markers able to denote disease characteristics in multiple sclerosis (MS) patients are still lacking. We applied a multivariate statistical analysis on results obtained by measuring-by real-time RT-PCR-mRNA levels of 25 immunological relevant molecules in PBMCs from 198 MS patients. The combined measurement of mRNA levels of IL-1beta, TNF-alpha, TGF-beta, CCL20 and CCR3 was able to distinguish MS patients from healthy individuals. CXCR5, CCL5, and CCR3 combined mRNA levels identify primary progressive MS patients while TNF-alpha, IL-10, CXCL10 and CCR3 differentiate relapsing MS patients. Our results indicate that multi-parametric analysis of mRNA levels of immunological relevant molecules in PBMCs may represent a successful strategy for the identification of putative peripheral markers of disease state and disease activity in MS patients.     

Insomnia in neurological diseases

Insomnia is the most common sleep complaint. Insomnia is not a disease itself but mostly a clinical sign of an underlying disease. Degenerative and vascular diseases involving the central nervous system (CNS) may impair sleep either as a result of the brain lesion or because of illness-related discomfort (motor immobility, social and familial impairment, depression, drugs). Some neurological conditions characterized by movement disorders that start or persist during sleep hinder sleep onset and/or sleep continuity, causing a poor sleep complaint. CNS lesions and/or dysfunction in three specific neurological conditions (fatal familial insomnia, Morvan's chorea, and delirium tremens) impair the basic mechanisms of sleep generation inducing a syndrome in which the inability to sleep is consistently associated with motor and sympathergic overactivation. Agrypnia excitata is the term that aptly defines this generalized overactivation syndrome.     

Benign focal liver lesions: spectrum of findings on SonoVue-enhanced pulse-inversion ultrasonography

The prevalence of benign focal liver lesions (BFLL) is high both in the general population and in patients with known malignancies. The gray-scale ultrasound (US) technique is usually the first-line imaging modality used in the radiological workup of such lesions, but unfortunately it lacks specificity. Furthermore, Doppler examination may often be unsatisfactory owing to motion artefacts, or when small or deeply located lesions are evaluated. Recently, microbubble-based contrast agents used in combination with gray-scale US techniques, which are very sensitive to nonlinear behavior of microbubbles, have led to a better depiction of both microvasculature and macrovasculature of focal hepatic masses, thus improving the reliability of using US in the assessment of liver tumors. This review illustrates the spectrum of enhancement patterns of BFLL on contrast-enhanced ultrasonography with SonoVue, a second-generation microbubble-based contrast agent.This paper is based on a work accepted for presentation as a scientific paper at the Scientific Assembly and Annual Meeting of the ECR 2004.