Prevalence of insulin resistance syndrome in southwestern France and its relationship with inflammatory and hemostatic markers

OBJECTIVE: To assess the prevalence and relationships of insulin resistance syndrome (IRS) with inflammatory and hemostatic markers in a representative sample of the population of Southwestern France aged 35-64 years. RESEARCH DESIGN AND METHODS: In this cross-sectional study, data were collected from 597 men and 556 women and were assessed regarding BMI, blood pressure, total and HDL cholesterol levels, triglyceride level, glucose level, plasma insulin level, white blood cell count, fibrinogen level, factor VII level, von Willebrand factor, C-reactive protein level, soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule-1, and soluble CD(14). Insulin resistance was defined by homeostasis model assessment > or =3.8. RESULTS: Prevalence of IRS was higher in men than in women (23 vs. 12%, respectively; P < 0.001) and increased with age in both sexes (9, 24, and 34% for age groups 35-44, 45-54, and 55-64 years, respectively, for men and 4, 10, and 21% for women). After adjusting for age, alcohol consumption, tobacco smoking, and also for menopause in women, subjects (men and women) with IRS had significantly higher white blood cell count, factor VII levels, coagulating factor VII levels, and C-reactive protein levels than the other subjects. In men, further increases in soluble intercellular adhesion molecule and soluble vascular cell adhesion molecule-1 were noted, whereas in women, the differences were borderline significant. Conversely, no differences were found in fibrinogen, von Willebrand factor, and soluble CD(14) in both sexes. CONCLUSIONS: IRS is relatively common in residents of Southwestern France and is related to a deleterious increase in hemostatic and inflammatory parameters.     

GSM-900MHz at low dose temperature-dependently downregulates α-synuclein in cultured cerebral cells independently of chaperone-mediated-autophagy

The expanding use of GSM devices has resulted in public concern. Chaperone-mediated autophagy (CMA) is a way for protein degradation in the lysosomes and increases under stress conditions as a cell defense response. α-synuclein, a CMA substrate, is a component of Parkinson disease. Since GSM might constitute a stress signal, we raised the possibility that GSM could alter the CMA process. Here, we analyzed the effects of chronic exposure to a low GSM-900MHz dose on apoptosis and CMA. Cultured cerebral cortical cells were sham-exposed or exposed to GSM-900MHz at specific absorption rate (SAR): 0.25W/kg for 24 h using a wire-patch cell. Apoptosis was analyzed by DAPI stain of the nuclei and western blot of cleaved caspase-3. The expression of proteins involved in CMA (HSC70, HSP40, HSP90 and LAMP-2A) and α-synuclein were analyzed by western blot. CMA was also quantified in situ by analyzing the cell localization of active lysosomes. 24 h exposure to GSM-900MHz resulted in ～0.5°C temperature rise. It did not induce apoptosis but increased HSC70 by 26% and slightly decreased HSP90 (<10%). It also decreased α-synuclein by 24% independently of CMA, since the localization of active lysosomes was not altered. Comparable effects were observed in cells incubated at 37.5°C, a condition that mimics the GSM-generated temperature rise. The GSM-induced changes in HSC70, HSP90 and α-synuclein are most likely linked to temperature rise. We did not observe any immediate effect on cell viability. However, the delayed and long term consequences (protective or deleterious) of these changes on cell fate should be examined.     

Distribution and identity of neurons expressing the oxytocin receptor in the mouse spinal cord

Nurr1 is a member of the nuclear receptor superfamily and is a regulatory factor of differentiation, migration and maturation of mesencephalic dopaminergic neurons. The present study was designed to observe the dynamic changes in the protein expression of Nurr1 and the relationship between Nurr1 and proliferating cell nuclear antigen (PCNA) during rat brain and spinal cord development. And we also investigated the significance of Nurr1 in differentiation and migration of nerve cells. Paraffin-embedded sections, immunohistochemistry, immunohistochemical double staining and Western blot techniques were used. The results demonstrate that the presence of Nurr1-positive cells increased during embryo development and that these cells slowly migrated to locations far from the lateral ventricle. In postnatal rats, the presence of Nurr1-positive cells surrounding the lateral ventricle decreased markedly. The expression of Nurr1 in the cerebral cortex peaked at postnatal days 1-5 (P1-P5) and then decreased as the cells matured, becoming rare in the mature cerebral cortex. As the cells matured, a staircase-shaped migration of Nurr1-positive cells from dorsal areas to ventral areas of the spinal cord could be observed. As maturation continued, the presence of Nurr1-positive cells in the spinal cord decreased, and no Nurr1-positive cells were found in the mature spinal cord. The comparative observation of Nurr1 and PCNA showed that the two proteins were expressed in different regions and in different cells. Nurr1 was confined to differentiated and migrating immature cells and was not present in proliferating cells. We suggest that Nurr1 may play a regulatory role in the differentiation, migration and maturation of nerve cells in the rat brain and spinal cord.     

A Duffy binding-like domain is involved in the NKp30-mediated recognition of Plasmodium falciparum-parasitized erythrocytes by natural killer cells

The recent demonstration that purified natural killer (NK) cells lyse Plasmodium falciparum-parasitized red blood cells (Pf-pRBCs) suggests that innate immunity is important in malaria. NK cell killing--presumably an early host response to infection--requires intimate contact between NK natural cytotoxicity receptors (NCRs) and ligands expressed on the surface of Pf-pRBCs. We investigated whether the Duffy binding-like (DBL)-1 alpha domain of P. falciparum erythrocyte membrane protein-1 (PfEMP-1) expressed on parasitized erythrocytes rendered Pf-pRBCs susceptible to NK cell lysis. We showed that with NKp30-immunoglobulin and NKp46-immunoglobulin fusion proteins and DBL-1alpha peptides NCRs are involved in the NK cell-Pf-pRBC interaction. This interaction was direct, specific, and functional, leading to perforin production and granzyme B release. The prior treatment of NK cells with DBL-1 alpha peptides abolished both this interaction and killing activity, suggesting that DBL-1 alpha -NCRs interaction is the key recognition mechanism leading to parasite killing by NK cells.