Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic circulatory, neurological, hematological, gastrointestinal, reproductive and immunological pathologies.  

The mechanism of lead induced toxity is not fully understood. The prime targets to lead toxicity are the heme synthesis enzymes, thiol-containing antioxidants and enzymes (superoxide dismutase, catalase, glutathione peroxidase, glucose 6-phosphate dehydrogenase and antioxidant molecules like GSH). The low blood lead levels are sufficient to inhibit the activity of these enzymes and induce generation of reactive oxygen species and intensification oxidative stress.  

Oxidative stress plays important role in pathogenesis of lead-induced toxity and pathogenesis of coupled disease. The primary target of lead toxicity is the central nervous system. There are different cellular, intracellular and molecular mechanisms of lead neurotoxicity: such as induction of oxidative stress, intensification of apoptosis of neurocites, interfering with Ca(2+) dependent enzyme like nitric oxide synthase.  

Population studies have demonstrated a link between lead exposure and subsequent development of hypertension and cardiovascular disease. The vascular endothelium is now regarded as the main target organ for the toxic effect of lead. Lead affects the vasoactive function of endothelium through the increased production of reactive oxygen species, inactivation of endogenous nitric oxide and downregulation of soluble guanylate cyclase by reactive oxygen species, leading to a limiting nitric oxide availability, impairing nitric oxide signaling.  

This review summarizes recent findings of the mechanism of the lead-induced toxity and possibilities of its prevention. 

Reference:  Nemsadze K, Sanikidze T, Ratiani L, Gabunia L, Sharashenidze T., Mechanisms of lead-induced poisoning, Tbilisi State Medical University; National Center of child development, Georgian Med News. 2009 Jul-Aug;(172-173):92-6.

The authors investigated the association of early-life exposure to indoor air pollution with neuropsychological development in preschoolers and assessed whether this association differs by glutathione-S-transferase gene (GSTP1) polymorphisms. A prospective, population-based birth cohort was set up in Menorca, Spain, in 1997-1999 (n = 482).

Children were assessed for cognitive functioning (McCarthy Scales of Children’s Abilities) and attention-hyperactivity behaviors (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) at age 4 years.

During the first 3 months of life, information about gas appliances at home and indoor nitrogen dioxide concentration was collected at each participant’s home (n = 398, 83%). Genotyping was conducted for the GSTP1 coding variant Ile105Val. Use of gas appliances was inversely associated with cognitive outcomes (beta coefficient for general cognition = -5.10, 95% confidence interval (CI): -9.92, -0.28; odds ratio for inattention symptoms = 3.59, 95% CI: 1.14, 11.33), independent of social class and other confounders.

Nitrogen dioxide concentrations were associated with cognitive function (a decrease of 0.27 point per 1 ppb, 95% CI: -0.48, -0.07) and inattention symptoms (odds ratio = 1.06, 95% CI: 1.01, 1.12).

The deleterious effect of indoor pollution from gas appliances on neuropsychological outcomes was stronger in children with the GSTP1 Val-105 allele. Early-life exposure to air pollution from indoor gas appliances may be negatively associated with neuropsychological development through the first 4 years of life, particularly among genetically susceptible children.

Reference: Morales E, Julvez J, Torrent M, de Cid R, Guxens M, Bustamante M, Künzli N, Sunyer J., Association of early-life exposure to household gas appliances and indoor nitrogen dioxide with cognition and attention behavior in preschoolers, Center for Research in Environmental Epidemiology, Barcelona, Catalonia, Spain, Am J Epidemiol. 2009 Jun 1;169(11):1327-36.

PET scans critical for early, accurate diagnosis and treatment of dementia, say researchers at SNM’s 56th Annual Meeting  

TORONTO—A new study shows that the use of positron emission tomography (PET) scans may improve the accuracy of dementia diagnoses early in disease onset for more than one out of four patients. The results were presented at SNM’s 56th Annual Meeting.  

Early, accurate diagnosis of dementia is critical for providing the best available courses of treatment and therapies in the beginning stages of disease, when treatments can be most effective. PET scans enable physicians to identify the neurological conditions underlying each patient’s mental decline and choose appropriate courses of treatment.

 “Routine clinical assessments do not accurately identify the root causes of dementia in the early stages,” said Kirk A. Frey, a physician with the University of Michigan Hospitals’ Division of Nuclear Medicine and lead author of the study. “Our preliminary results clearly indicate that molecular imaging technologies, such as PET scans, can help diagnose a patient’s specific type of dementia. This is critical for providing the best possible care. Additionally, PET’s ability to pinpoint neurological underpinnings of different forms of dementia could lead to new, more targeted drugs and therapies.”

More than 5 million people each year are newly diagnosed with dementia, a disease that takes many forms and includes memory loss or other mental impairments that interfere with daily life. The most common type of dementia is Alzheimer’s disease. Other types include frontotemporal dementia, which affects the frontal and temporal lobes of the brain, and Lewy body dementia, which involves degeneration of dopamine nerves in addition to the temporal and parietal lobes. Although these types of dementia have different causes, patients can express similar symptoms in the early stages, making accurate diagnosis difficult. Providing appropriate treatments and therapies as early as possible can avoid unnecessary, and sometimes severe, side-effects and complications.  

The new study identified 66 patients with mild dementia or mild cognitive impairment who were evaluated through standard neurological testing and anatomic brain imaging. Three clinical experts reviewed the results of these data to make diagnoses of either Alzheimer’s disease, frontotemporal dementia or dementia with Lewy bodies. Patients then underwent PET scans for amyloid deposits and for dopamine nerve integrity. Patients’ initial diagnoses changed more than 25 percent of the time after PET imaging. PET scans provided images of important signals for disease that other examinations missed, such as deposits of amyloid plaque, which are a common indicator of Alzheimer’s disease, and damage to dopamine nerves in Lewy body dementia.  

The study will track patients for two years to confirm the accuracy of their diagnoses. 

Reference:

Scientific Paper 251: K. Frey, J. Burke, B. Giodani, R. Koeppe, R. Albin, The University of Michigan, Ann Arbor, MI; “PET neurochemical vs. clinical phenotypes in mild-early dementia,” SNM’s 56th Annual Meeting, June 13-17, 2009.

SNM – Society of Nuclear Medicine, PET Scans May Improve Accuracy of Dementia Diagnosis, June 10, 2009

About SNM – Advancing Molecular Imaging and Therapy

SNM is an international scientific and medical organization dedicated to raising public awareness about what molecular imaging is and how it can help provide patients with the best health care possible. SNM members specialize in molecular imaging, a vital element of today’s medical practice that adds an additional dimension to diagnosis, changing the way common and devastating diseases are understood and treated.  

SNM’s more than 17,000 members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings and leading advocacy on key issues that affect molecular imaging and therapy research and practice. For more information, visit www.snm.org.

Paris, France – June 04, 2009 – The cause of Parkinson’s disease (PD), the second most frequent neurodegenerative disease after Alzheimer’s disease, is unknown, but in most cases it is believed to involve a combination of environmental risk factors and genetic susceptibility. Laboratory studies in rats have shown that injecting the insecticide rotenone leads to an animal model of PD and several epidemiological studies have shown an association between pesticides and PD, but most have not identified specific pesticides or studied the amount of exposure relating to the association.  

A new epidemiological study involving the exposure of French farm workers to pesticides found that professional exposure is associated with PD, especially for organochlorine insecticides. The study is published in Annals of Neurology, the official journal of the American Neurological Association.  

Led by Alexis Elbaz M.D., Ph.D., of Inserm, the national French institute for health research in Paris, and University Pierre et Marie Curie (UPMC, Paris 6), the study involved individuals affiliated with the French health insurance organization for agricultural workers who were frequently exposed to pesticides in the course of their work. Occupational health physicians constructed a detailed lifetime exposure history to pesticides by interviewing participants, visiting farms, and collecting a large amount of data on pesticide exposure. These included farm size, type of crops, animal breeding, which pesticides were used, time period of use, frequency and duration of exposure per year, and spraying method. 

The study found that PD patients had been exposed to pesticides through their work more frequently and for a greater number of years/hours than those without PD. Among the three main classes of pesticides (insecticides, herbicides, fungicides), researchers found the largest difference for insecticides: men who had used insecticides had a two-fold increase in the risk of PD. 

“Our findings support the hypothesis that environmental risk factors such as professional pesticide exposure may lead to neurodegeneration,” notes Dr. Elbaz.  

The study highlights the need to educate workers applying pesticides as to how these products should be used and the importance of promoting and encouraging the use of protective devices. In addition to the significance of the study for those with a high level of exposure to pesticides, it also raises the question about the role of lower-level environmental exposure through air, water and food, and additional studies are needed to address this question.  

Reference: Alexis Elbaz, Jacqueline Clavel, Paul J. Rathouz, PhD 6, Frédéric Moisan Jean-Philippe Galanaud, Bernard Delemotte, Annick Alpérovitch, Christophe Tzourio, Professional exposure to pesticides and Parkinson’s disease, Annals of Neurology, Press Release Wiley Blackwell, June 4, 2009