[Chelating agents : alert to misuses!] / Les agents chélateurs : alerte à l'abus !

Exposure to heavy metals is a common phenomenon due to their prevalence in food and environment; their toxicity remains a major concern for public health. Chelating agents are drugs used to increase the elimination of metals present at abnormally high levels in the body. Their approved clinical indications are limited, particularly because of their potential adverse effects. Unfortunately, too often, chelating agents are used to test the body impregnation level by heavy metals. It is an inappropriate and abusive use. In order to attract attention to this problematic, the good and bad uses of metal chelators are reviewed.

L'exposition aux métaux lourds est un phénomène courant en raison de leur prévalence dans l'alimentation et dans l'environnement; leur toxicité demeure une préoccupation importante pour la santé publique. Les agents chélateurs sont des substances chimiques utilisées pour augmenter l'élimination de certains métaux présents à des concentrations anormalement élevées dans l'organisme. Leurs indications cliniques approuvées sont limitées, particulièrement en raison des effets indésirables qu'ils peuvent induire. Malheureusement, trop souvent, les agents chélateurs sont utilisés avec pour objectif de vérifier le niveau d'imprégnation de l'organisme par les métaux lourds. Il s'agit d'un usage inapproprié et abusif. Afin d'attirer l'attention des praticiens sur cette problématique, les bons et les mauvais usages des chélateurs de métaux sont passés en revue.

Zinc or albendazole attenuates the progression of environmental enteropathy: a randomized controlled trial.

BACKGROUND & AIMS: Environmental enteropathy (EE) is a subclinical condition among children in the developing world, characterized by T-cell infiltration of the small-bowel mucosa and diffuse villous atrophy. EE leads to macronutrient and micronutrient malabsorption and stunting, with a resultant increased risk for infection and reduced cognitive development. We tested the hypothesis that zinc and albendazole treatments would reduce the severity of EE in rural African children. METHODS: In a randomized, double-blind, placebo-controlled trial in rural southern Malawi, asymptomatic children, 1 to 3 years old and at high risk for EE, received either a single dose of albendazole, a 14-day course of 20 mg zinc sulfate, or a placebo. Subjects were given the dual-sugar absorption test, and the ratio of lactulose to mannitol (L:M) in urine was used to determine the severity of EE at baseline and 34 days after completion of the assigned regimen. The primary outcome was the change in the L:M. RESULTS: A complete set of urine samples was obtained from 222 of 234 children enrolled and analyzed. The mean baseline L:M was 0.32 ± 0.18 among all children and did not differ among groups (normal L:M range, <0.12). At the end of the study, the L:M ratio had increased more in the placebo group (0.12 ± 0.31) than in the zinc group (0.03 ± 0.20; P < .03) or the albendazole group (0.04 ± 0.22; P < .04). CONCLUSIONS: Treatment with zinc or albendazole protects against a significant increase in the L:M ratio, a biomarker for EE, in asymptomatic rural Malawian children. These findings could provide insight into the etiology and pathogenesis of EE. Clinicaltrials.gov Number: NCT01440608.

[Efficacy of immunomodulators in children with respiratory diseases in environmentally poor areas].

The authors evaluated the clinical efficacy and safety of the antiviral and immunomodulatory drug Isoprinosine (inosine pranobex, Teva Pharmaceutical Industries, Ltd) in the treatment of bronchopulmonary diseases in children. One hundred and fifty-two children with acute respiratory diseases and an exacerbation of recurrent respiratory diseases were followed up. The use of Isoprinosine in their combined treatment showed both positive clinical changes and a better immunogram.

Inhaled corticosteroid adherence in paediatric patients: the PACMAN cohort study.

AIMS: Poor adherence with inhaled corticosteroids (ICSs) has been reported frequently and may be associated with uncontrolled asthma. A better understanding of factors influencing adherence may help to achieve higher adherence rates for a larger part of the population, which will eventually lead to better asthma control. The aim of this study was to investigate factors associated with adherence in paediatric ICS users. METHODS: We included 527 children using ICSs who participated in the Pharmacogenetics of Asthma Medication in Children: Medication with Anti-inflammatory Effects (PACMAN) cohort study. The outcome, a parent-reported adherence, was assessed by using the Medication Adherence Report Scale. Four categories of determinants were studied: child characteristics, family characteristics, medication use (parental beliefs towards medication; using Beliefs about Medicines Questionnaire) and environmental factors. RESULTS: Good adherence was observed in 302 children (57%). Increased fractional exhaled nitric oxide values (indication for airway inflammation) were associated with a lower chance of good adherence (OR = 0.25, 95%CI = 0.15-0.41). Parental necessity beliefs about medication were associated with higher adherence (OR = 2.32, 95%CI = 1.59-3.39). Dutch origin was also associated with higher adherence rates (OR = 2.11, 95%CI = 1.09-4.07). Furthermore, younger age (< 6 years) was associated with better adherence (OR = 1.62, 95%CI = 1.02-2.59). CONCLUSIONS: Increased airway inflammation was associated with lower ICS adherence, which underlines the need of good adherence to reach disease control. Our results suggest that by improving knowledge, especially in ethnic minorities, and by stimulating positive parental perception towards the nature of the disease, the characteristics of the prescribed drugs and the use of medications, better adherence and as a result better asthma control could be reached.

Ayurvedic herbal supplements as an antidote to 9/11 toxicity.

An in-treatment web-based survey was conducted in 2005 with 50 New York World Trade Center rescue and recovery workers, volunteers, and area residents and workers who were treated with Ayurvedic herbs for post-9/11 symptoms. The survey documented pretreatment efforts at symptom relief, post-treatment symptom impact, and the context for using the herbal intervention. Herbal treatment was administered and monitored by a private non-profit organization. The natural detoxification and immune-strengthening program consists of 4 herbal supplements developed by an Ayurvedic physician. A minimum 6-month basic program was recommended, but many participants continued to 1 year and longer. All 50 respondents reported high incidence of alleviation of previously intractable symptoms, chiefly respiratory symptoms, fatigue, and depression.

The effect of supplementary antioxidant therapy in patients who report hypersensitivity to electricity: a randomized controlled trial.

CONTEXT: Hypersensitivity to electricity is a proposed environmental illness of unknown etiology. Patients report a variety of symptoms that they relate to electric equipment. The afflicted individuals suffer from ill health. Many interventions have been tried but, to date, there is no one specific treatment that has been proven superior to other remedial actions. In general, there is a lack of controlled prospective studies. OBJECTIVE: To test the hypothesis that antioxidant therapy reduces symptoms and improves health in patients reporting hypersensitivity to electricity. DESIGN: Randomized, double-blind, crossover, placebo-controlled study. SETTING: Patients referred to the Environmental Illness Research Centre, Stockholm County Council. PATIENTS: Sixteen patients reporting hypersensitivity to electricity. INTERVENTION: Antioxidant supplementation (vitamins C and E, selenium). MAIN OUTCOME MEASURES: Self-reported symptoms and reported degree of hypersensitivity to electricity, serum levels of uric acid and diphenylpycrylhydrazyl (DPPH). RESULTS: The results indicated no significant differences in reported symptoms, reported hypersensitivity to electricity, or oxidative status in serum between periods of antioxidant and placebo treatments. Serum levels of DPPH and uric acid showed no correlation with the reported degree of symptoms or hypersensitivity to electricity. CONCLUSIONS: The study did not show any beneficial effect of antioxidant supplementation for patients reporting hypersensitivity to electricity. The results do not support the hypothesis that oxidative stress is a major contributor to ill health in patients who report hypersensitivity to electricity.

Placebo response in environmental disease. Chelation therapy of patients with symptoms attributed to amalgam fillings.

Treatment of patients who attribute their environmental illness to mercury from amalgam fillings is largely experimental. On the Symptom Check List, overall distress, and somatization, obsessive-compulsive, depression, and anxiety symptom dimensions, were increased in 50 consecutive patients examined, and Eysenck Personality Questionnaire scores suggested less extroversion and increased degree of emotional liability. Succimer (meso-2, 3-dimercaptosuccinic acid) was given at a daily dose of 30 mg/kg for five days in a double-blind, randomized placebo-controlled trial. Urinary excretion of mercury and lead was considerably increased in the patients who received the chelator. Immediately after the treatment and 5 to 6 weeks later, most distress dimensions had improved considerably, but there was no difference between the succimer and placebo groups. These findings suggest that some patients with environmental illness may substantially benefit from placebo.