Elevated Blood Lead Concentrations in Essential Tremor: A Case–Control Study in Mersin, Turkey

Essential tremor (ET) is one of the most common neurologic disorders. Aside from underlying susceptibility genes, recent studies have also begun to focus on environmental toxic factors. Yet there remains a paucity of information on such factors, making studies of environmental factors important. A recent study in New York City found blood lead concentrations to be elevated in ET cases compared with matched controls. Chronic exposure to lead produces cerebellar damage, and this could predispose individuals to develop ET

Association between essential tremor and blood lead concentration

Lead is a ubiquitous toxicant that causes tremor and cerebellar damage. Essential tremor (ET) is a highly prevalent neurologic disease associated with cerebellar involvement. Although environmental toxicants may play a role in ET etiology and their identification is a critical step in disease prevention, these toxicants have received little attention. Our objective was to test the hypothesis that ET is associated with lead exposure. Therefore, blood lead (BPb) concentrations were measured and a lifetime occupational history was assessed in ET patients and in controls. We frequency matched 100 ET patients and 143 controls on age, sex, and ethnicity. BPb concentrations were analyzed using graphite furnace atomic absorption spectrophotometry. A lifetime occupational history was reviewed by an industrial hygienist. BPb concentrations were higher in ET patients than in controls (mean ± SD, 3.3 ± 2.4 and 2.6 ± 1.6 µg/dL, respectively; median, 2.7 and 2.3 µg/dL; p = 0.038). In a logistic regression model, BPb concentration was associated with diagnosis [control vs. ET patient, odds ratio (OR) per unit increase = 1.21; 95% confidence interval (CI), 1.05-1.39; p = 0.007]. BPb concentration was associated with diagnosis (OR per unit increase = 1.19; 95% CI, 1.03-1.37; p = 0.02) after adjusting for potential confounders. Prevalence of lifetime occupational lead exposure was similar in ET patients and controls. We report an association between BPb concentration and ET. Determining whether this association is due to increased exposure to lead or a difference in lead kinetics in ET patients requires further investigation

What type of problem is waste in Egypt?

International audienceThis paper attempts to show that while the production of waste may be universal, the threat it poses is not. In order to explain and justify the question 'what type of problem is waste', the paper begins by attempting to, first, provincialise the 'environmental' framing of waste by examining the category's historically changing problematisations in Western Europe and North America, and, second, through a critique of Mary Douglas's work Purity and danger, to argue that waste should be theorised ethnographically rather than analytically. It then argues that, in Egypt, the materiality of litter and the sociality of waste work are sublimated into a religio-civilisational register based on the central trope of cleanliness rather than environment. It does so by considering various meanings and inflexions of the word 'cleanliness' in vernacular usage, the way the terms environment and pollution are used, naming conventions for waste collectors and anti-litter campaigns

Insulin Signaling and Insulin Sensitizing in Muscle and Liver of Obese Monkeys: Peroxisome Proliferator-Activated Receptor Gamma Agonist Improves Defective Activation of Atypical Protein Kinase C

Obesity, the metabolic syndrome, and aging share several pathogenic features in both humans and non-human primates, including insulin resistance and inflammation. Since muscle and liver are considered key integrators of metabolism, we sought to determine in biopsies from lean and obese aging rhesus monkeys the nature of defects in insulin activation and, further, the potential for mitigation of such defects by an in vivo insulin sensitizer, rosiglitazone, and a thiazolidinedione activator of the peroxisome proliferator-activated receptor gamma. The peroxisome proliferator-activated receptor gamma agonist reduced hyperinsulinemia, improved insulin sensitivity, lowered plasma triglycerides and free fatty acids, and increased plasma adiponectin. In muscle of obese monkeys, previously shown to exhibit defective insulin signaling, the insulin sensitizer improved insulin activation of atypical protein kinase C (aPKC), the defective direct activation of aPKC by phosphatidylinositol (PI)-3,4,5-(PO4)3, and 5′-AMP-activated protein kinase and increased carnitine palmitoyltransferase-1 mRNA expression, but it did not improve insulin activation of insulin receptor substrate (IRS)-1-dependent PI 3-kinase (IRS-1/PI3K), protein kinase B, or glycogen synthase. We found that, although insulin signaling was impaired in muscle, insulin activation of IRS-1/PI3K, IRS-2/PI3K, protein kinase B, and aPKC was largely intact in liver and that rosiglitazone improved insulin signaling to aPKC in muscle by improving responsiveness to PI-3,4,5-(PO4)3. Antioxid. Redox Signal. 14, 207–219

Compared Effect of Immunosuppressive Drugs Cyclosporine A and Rapamycin on Cholesterol Homeostasis Key Enzymes CYP27A1 and HMG-CoA Reductase

International audienceHyperlipidaemia, i.e. increase in total cholesterol and triglycerides, is a common side-effect of the immunosuppressive drugs rapamycin (RAPA) and cyclosporine A (CsA), and is probably related to inhibition of the 27-hydroxylation of cholesterol (acid pathway of bile acid biosynthesis). This might be one of the causes for the increase in plasma cholesterol, as 27-hydroxycholesterol is a potent suppressor of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), a key enzyme of cholesterol synthesis. As the sterol 27-hydroxylase (CYP27A1) inhibition by CsA is well known, we evaluated the effect of another immunosuppressive drug, RAPA, on this enzyme in HepG2 mitochondria, which confirmed the dose-dependent inhibition of mitochondrial CYP27A1 by cyclosporine (10-20 µ M), while the inhibition by RAPA required a higher dose (50-100 µ M). Corresponding K i was 10 µ M for CsA (non-competitive inhibition) and 110 µ M for RAPA (competitive inhibition). Cotreatment with both immunosuppressive drugs showed an additive inhibitory effect on CYP27A1 activity. Later, we analysed the effect of these immunosuppressants on HMGR expression in HepG2 cells, and a dose-dependent up-regulation of HMGR gene expression was observed. The results suggest that RAPA and CsA are both inhibitors of CYP27A1 activity with slightly different mechanisms and that they may accordingly increase HMGR expression