ABSTRACT
From a cohort of 2018 evaluable consecutive cases issued from the European Clinical Trial Database, we describe the complete clinical symptomatic presentation of electrohypersensitivity (EHS) and multiple chemical sensitivity (MCS) and their association in the framework of a unique, sensitivity-related environmental neurologic syndrome. Eligibility criteria are those of the Atlanta consensus meeting for MCS, and those of WHO for EHS. There were 1428 EHS, 85 MCS and 505 EHS/MCS evaluable cases, so EHS was associated with MCS in 25%. Women appeared to be much more susceptible to EHS and/or to MCS than men, with no statistical significance between the EHS and MCS groups (p = 0.07), but the combined group revealed a more significant female sex ratio of 80.4% (p < 0.0001). All symptoms except emotional behavior were significantly more frequent in EHS patients than in healthy controls (p < 0.0001). We found no pathognomonic symptoms to establish the diagnosis of both disorders or to distinguish EHS from MCS. The three groups of patients were found to share identical symptoms, while several symptoms were found to be more significantly frequent in EHS/MCS than in EHS (p < 0.0001). From these data, we suggest that EHS and MCS are new brain disorders, generated via a common etiopathogenic mechanism.
ABSTRACT
Much of the controversy over the cause of electrohypersensitivity (EHS) lies in the absence of recognized clinical and biological criteria for a widely accepted diagnosis. However, there are presently sufficient data for EHS to be acknowledged as a distinctly well-defined and objectively characterized neurologic pathological disorder. Because we have shown that 1) EHS is frequently associated with multiple chemical sensitivity (MCS) in EHS patients, and 2) that both individualized disorders share a common pathophysiological mechanism for symptom occurrence; it appears that EHS and MCS can be identified as a unique neurologic syndrome, regardless their causal origin. In this overview we distinguish the etiology of EHS itself from the environmental causes that trigger pathophysiological changes and clinical symptoms after EHS has occurred. Contrary to present scientifically unfounded claims, we indubitably refute the hypothesis of a nocebo effect to explain the genesis of EHS and its presentation. We as well refute the erroneous concept that EHS could be reduced to a vague and unproven "functional impairment". To the contrary, we show here there are objective pathophysiological changes and health effects induced by electromagnetic field (EMF) exposure in EHS patients and most of all in healthy subjects, meaning that excessive non-thermal anthropogenic EMFs are strongly noxious for health. In this overview and medical assessment we focus on the effects of extremely low frequencies, wireless communications radiofrequencies and microwaves EMF. We discuss how to better define and characterize EHS. Taken into consideration the WHO proposed causality criteria, we show that EHS is in fact causally associated with increased exposure to man-made EMF, and in some cases to marketed environmental chemicals. We therefore appeal to all governments and international health institutions, particularly the WHO, to urgently consider the growing EHS-associated pandemic plague, and to acknowledge EHS as a mainly new real EMF causally-related pathology.
Subject(s)
Multiple Chemical Sensitivity , Nervous System Diseases , Electromagnetic Fields/adverse effects , Humans , Microwaves , Multiple Chemical Sensitivity/diagnosis , Multiple Chemical Sensitivity/epidemiology , Multiple Chemical Sensitivity/etiology , Radio WavesABSTRACT
Clinical research aiming at objectively identifying and characterizing diseases via clinical observations and biological and radiological findings is a critical initial research step when establishing objective diagnostic criteria and treatments. Failure to first define such diagnostic criteria may lead research on pathogenesis and etiology to serious confounding biases and erroneous medical interpretations. This is particularly the case for electrohypersensitivity (EHS) and more particularly for the so-called "provocation tests", which do not investigate the causal origin of EHS but rather the EHS-associated particular environmental intolerance state with hypersensitivity to man-made electromagnetic fields (EMF). However, because those tests depend on multiple EMF-associated physical and biological parameters and have been conducted in patients without having first defined EHS objectively and/or endpoints adequately, they cannot presently be considered to be valid pathogenesis research methodologies. Consequently, the negative results obtained by these tests do not preclude a role of EMF exposure as a symptomatic trigger in EHS patients. Moreover, there is no proof that EHS symptoms or EHS itself are caused by psychosomatic or nocebo effects. This international consensus report pleads for the acknowledgement of EHS as a distinct neuropathological disorder and for its inclusion in the WHO International Classification of Diseases.
Subject(s)
Biomarkers/metabolism , Hypersensitivity/metabolism , Multiple Chemical Sensitivity/metabolism , Animals , Consensus , Diagnostic Imaging/methods , Diagnostic Tests, Routine/methods , Electromagnetic Fields , Humans , Nervous System Diseases/metabolismABSTRACT
Since the 1956 hypothesis of Otto Warburg, aerobic glycolysis has been recognized as a metabolic hallmark of cancer. Because methylglyoxal (MG) is a naturally occurring waste metabolite of glycolysis, we measured blood levels of this molecule in colon cancer-bearing rats. To compare the blood levels of free MG in cancerous and healthy animals,the present study used a dedicated tumor graft model consisting of the subcutaneous administration in syngenic BD-IX rats of a tumorigenic cell clone (PROb) and another non-tumorigenic clone (REGb) derived from the same tumor. Rats grafted with the PROb growing tumor cell clone exhibited a statistically significant increase in free MG blood levels (P=0.003), whereas rats transplanted with the REGb non-growing tumor cell clone exhibited normal MG values. The present study (first of three parts) suggests that cancer cells can produce and release free MG at higher levels than normal cells, making MG a putative novel metabolic biomarker of cancer.
ABSTRACT
Since 2009, we built up a database which presently includes more than 2000 electrohypersensitivity (EHS) and/or multiple chemical sensitivity (MCS) self-reported cases. This database shows that EHS is associated in 30% of the cases with MCS, and that MCS precedes the occurrence of EHS in 37% of these EHS/MCS-associated cases. EHS and MCS can be characterized clinically by a similar symptomatic picture, and biologically by low-grade inflammation and an autoimmune response involving autoantibodies against O-myelin. Moreover, 80% of the patients with EHS present with one, two, or three detectable oxidative stress biomarkers in their peripheral blood, meaning that overall these patients present with a true objective somatic disorder. Moreover, by using ultrasonic cerebral tomosphygmography and transcranial Doppler ultrasonography, we showed that cases have a defect in the middle cerebral artery hemodynamics, and we localized a tissue pulsometric index deficiency in the capsulo-thalamic area of the temporal lobes, suggesting the involvement of the limbic system and the thalamus. Altogether, these data strongly suggest that EHS is a neurologic pathological disorder which can be diagnosed, treated, and prevented. Because EHS is becoming a new insidious worldwide plague involving millions of people, we ask the World Health Organization (WHO) to include EHS as a neurologic disorder in the international classification of diseases.
Subject(s)
Biomarkers/blood , Multiple Chemical Sensitivity/diagnostic imaging , Nervous System Diseases/diagnostic imaging , Electromagnetic Fields/adverse effects , Humans , Middle Cerebral Artery/diagnostic imaging , Middle Cerebral Artery/metabolism , Multiple Chemical Sensitivity/complications , Multiple Chemical Sensitivity/metabolism , Nervous System Diseases/etiology , Nervous System Diseases/metabolism , Oxidative Stress , Self Report , Ultrasonography, Doppler, TranscranialABSTRACT
A total of 32 electrohypersensitivity (EHS) selfreporting patients were serially included in the present prospective study for oxidative stress and antioxidative stress response assessment. All thiobarbituric acidreactive substances (TBARs) were measured in the plasma, particularly malondialdehyde (MDA) for lipid peroxidation; additional measurements included total thiol group molecules, reduced glutathione (GSH), oxidized glutathione (GSSG) for oxidative stress assessment and nitrotyrosine, a marker of peroxynitriteinduced oxidative/nitrosative stress. In addition, the activity of CuZn superoxide dismutase (SOD1) was measured in red blood cells (RBCs) and glutathione reductase (GR) and glutathione peroxidase (GPx) in RBCs and plasma. Depending of the biomarker considered, 3050% of EHS selfreporting patients presented statistically significantly increased TBARs, MDA, GSSG and NTT mean plasmatic level values in comparison with normal values obtained in healthy controls (P<0.0001). By contrast, there were no plasmatic level values above the upper normal limits for GSH, GSH/GSSG ratio, total glutathione (GluT) and GSH/GluT ratio, and values for these GSHassociated biomarkers were statistically significantly decreased in 2040% of the patients (P<0.0001). Furthermore, in RBCs, mean SOD1 and GPx activities were observed to be statistically significantly increased in ~60% and 19% (P<0.0001) of the patients, respectively, while increased GR activity in RBCs was observed in only 6% of the patients. The present study reports for the first time, to the best of our knowledge, that overall ~80% of EHS selfreporting patients present with one, two or three detectable oxidative stress biomarkers in their peripheral blood, meaning that these patientsas is the case for cancer, Alzheimer's disease or other pathological conditionspresent with a true objective new pathological disorder.
Subject(s)
Erythrocytes/metabolism , Glutathione Disulfide/blood , Glutathione Peroxidase/blood , Glutathione Reductase/blood , Oxidative Stress , Self Report , Superoxide Dismutase-1/blood , Adolescent , Adult , Aged , Biomarkers/blood , Female , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
A careful molecular biology, epidemiological and mathematical modelling reanalysis of the recently published study titled 'Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions' by Cristian Tomasetti and Bert Vogelstein, which was published on January 2, 2015 in the distinguished journal Science, led to the conclusion that, contrary to the authors' claim, many cancer types are not caused by replicative random mutations. Rather than the authors' two arbitrarily individualized groups of cancer, a three-group model is herein proposed in the framework of this technical comment, considerably reducing the fraction of cancer cases hypothetically attributable to random mutations.
ABSTRACT
Much of the controversy over the causes of electro-hypersensitivity (EHS) and multiple chemical sensitivity (MCS) lies in the absence of both recognized clinical criteria and objective biomarkers for widely accepted diagnosis. Since 2009, we have prospectively investigated, clinically and biologically, 1216 consecutive EHS and/or MCS-self reporting cases, in an attempt to answer both questions. We report here our preliminary data, based on 727 evaluable of 839 enrolled cases: 521 (71.6%) were diagnosed with EHS, 52 (7.2%) with MCS, and 154 (21.2%) with both EHS and MCS. Two out of three patients with EHS and/or MCS were female; mean age (years) was 47. As inflammation appears to be a key process resulting from electromagnetic field (EMF) and/or chemical effects on tissues, and histamine release is potentially a major mediator of inflammation, we systematically measured histamine in the blood of patients. Near 40% had a increase in histaminemia (especially when both conditions were present), indicating a chronic inflammatory response can be detected in these patients. Oxidative stress is part of inflammation and is a key contributor to damage and response. Nitrotyrosin, a marker of both peroxynitrite (ONOO°-) production and opening of the blood-brain barrier (BBB), was increased in 28% the cases. Protein S100B, another marker of BBB opening was increased in 15%. Circulating autoantibodies against O-myelin were detected in 23%, indicating EHS and MCS may be associated with autoimmune response. Confirming animal experiments showing the increase of Hsp27 and/or Hsp70 chaperone proteins under the influence of EMF, we found increased Hsp27 and/or Hsp70 in 33% of the patients. As most patients reported chronic insomnia and fatigue, we determined the 24 h urine 6-hydroxymelatonin sulfate (6-OHMS)/creatinin ratio and found it was decreased (<0.8) in all investigated cases. Finally, considering the self-reported symptoms of EHS and MCS, we serially measured the brain blood flow (BBF) in the temporal lobes of each case with pulsed cerebral ultrasound computed tomosphygmography. Both disorders were associated with hypoperfusion in the capsulothalamic area, suggesting that the inflammatory process involve the limbic system and the thalamus. Our data strongly suggest that EHS and MCS can be objectively characterized and routinely diagnosed by commercially available simple tests. Both disorders appear to involve inflammation-related hyper-histaminemia, oxidative stress, autoimmune response, capsulothalamic hypoperfusion and BBB opening, and a deficit in melatonin metabolic availability; suggesting a risk of chronic neurodegenerative disease. Finally the common co-occurrence of EHS and MCS strongly suggests a common pathological mechanism.
Subject(s)
Biomarkers/metabolism , Hypersensitivity/diagnosis , Inflammation/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Biomarkers/urine , Electromagnetic Fields/adverse effects , Female , Humans , Hypersensitivity/etiology , Inflammation/etiology , Male , Middle Aged , Multiple Chemical Sensitivity/diagnosis , Multiple Chemical Sensitivity/etiology , Radio Waves/adverse effects , Young AdultABSTRACT
Metabolic syndrome and type 2 diabetes are associated with increased risk of breast cancer development and progression. Methylglyoxal (MG), a glycolysis by-product, is generated through a non-enzymatic reaction from triose-phosphate intermediates. This dicarbonyl compound is highly reactive and contributes to the accumulation of advanced glycation end products. In this study, we analyzed the accumulation of Arg-pyrimidine, a MG-arginine adduct, in human breast adenocarcinoma and we observed a consistent increase of Arg-pyrimidine in cancer cells when compared with the non-tumoral counterpart. Further immunohistochemical comparative analysis of breast cancer subtypes revealed that triple negative lesions exhibited low accumulation of Arg-pyrimidine compared with other subtypes. Interestingly, the activity of glyoxalase 1 (Glo-1), an enzyme that detoxifies MG, was significantly higher in triple negative than in other subtype lesions, suggesting that these aggressive tumors are able to develop an efficient response against dicarbonyl stress. Using breast cancer cell lines, we substantiated these clinical observations by showing that, in contrast to triple positive, triple negative cells induced Glo-1 expression and activity in response to MG treatment. This is the first report that Arg-pyrimidine adduct accumulation is a consistent event in human breast cancer with a differential detection between triple negative and other breast cancer subtypes.
Subject(s)
Arginine/metabolism , Lactoylglutathione Lyase/metabolism , Pyrimidines/metabolism , Pyruvaldehyde/metabolism , Triple Negative Breast Neoplasms/metabolism , Cell Line, Tumor , Female , Glycation End Products, Advanced/metabolism , Humans , Immunohistochemistry , MCF-7 Cells , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathologyABSTRACT
Prostate cancer incidence is steadily increasing in many developed countries. Because insular populations present unique ethnic, geographical, and environmental characteristics, we analyzed the evolution of prostate cancer age-adjusted world standardized incidence rates in Martinique in comparison with that of metropolitan France. We also compared prostate cancer incidence rates, and lifestyle-related and socioeconomic markers such as life expectancy, dietary energy, and fat supply and consumption, with those in other Caribbean islands, France, UK, Sweden, and USA. The incidence rate of prostate cancer in Martinique is one of the highest reported worldwide; it is continuously growing since 1985 in an exponential mode, and despite a similar screening detection process and lifestyle-related behaviour, it is constantly at a higher level than in metropolitan France. However, Caribbean populations that are genetically close to that of Martinique have generally much lower incidence of prostate cancer. We found no correlation between prostate cancer incidence rates, life expectancy, and diet westernization. Since the Caribbean African descent-associated genetic susceptibility factor would have remained constant during the 1980-2005, we suggest that in Martinique some environmental change including the intensive use of carcinogenic organochlorine pesticides might have occurred as key determinant of the persisting highly growing incidence of prostate cancer.
ABSTRACT
Exogenous chemical carcinogenesis is an extremely complex multifactorial process during which gene-environment interactions involving chronic exposure to exogenous chemical carcinogens (ECCs) and polymorphisms of cancer susceptibility genes add further complexity. We describe the properties and molecular mechanisms of ECCs that contribute to induce and generate cancer. A basic and specific property of many lipophilic organic ECCs including polycyclic aromatic hydrocarbons and polyhalogenated aromatic hydrocarbons is their ability to bioaccumulate in the adipose tissue from where they may be released in the blood circulation and target peripheral tissues for carcinogenesis. Many organic ECCs are procarcinogens and consequently need to be activated by the cytochrome P450 (CYP) system and/or other enzymes before they can adduct DNA and proteins. Because they contribute not only to the cocarcinogenic and promoting effects of many aromatic pollutants but also to their mutagenic effects, the aryl hydrocarbon receptor-activating and the inducible CYP systems are central to exogenous chemical carcinogenesis. Another basic property of ECCs is their ability to induce stable and bulky DNA adducts that cannot be simply repaired by the different repair systems. In addition, following ECC exposure, mutagenesis may also be caused indirectly by free-radical production and by epigenetic alterations. As a result of complex molecular interplays, direct and/or indirect mutagenesis may especially account for the carcinogenic effects of many exogenous metals and metalloids. Because of these molecular properties and action mechanisms, we conclude that ECCs could be major contributors to human cancer, with obviously great public health consequences.
Subject(s)
Carcinogens, Environmental , Carcinogens/pharmacology , Neoplasms/chemically induced , HumansABSTRACT
Benzo[a]pyrene (B[a]P) is a common food pollutant that causes DNA adduct formation and is carcinogenic. The report of a positive correlation between human plasma B[a]P levels and body mass index, together with B[a]P's lipophilicity, led us to test for possible adverse effects of B[a]P on adipose tissue. In ex vivo experiments using primary murine adipocytes, B[a]P rapidly (within minutes) and directly inhibited epinephrine-induced lipolysis (up to 75%) in a dose-dependent manner. Half-maximum inhibition was obtained with a B[a]P concentration of 0.9 mg.L(-1) (3.5 microm). Lipolysis induced by beta(1)-, beta(2)- and beta(3)-adrenoreceptor-specific agonists, as well as ACTH, were also significantly inhibited by B[a]P, whereas forskolin-induced lipolysis was not B[a]P-sensitive. Similar inhibition of catecholamine-induced lipolysis by B[a]P was also seen in isolated human adipocytes; half-maximum inhibition of lipolysis was achieved with a B[a]P concentration of 0.02 mg.L(-1) (0.08 microm). In vivo treatment of C57Bl/6J mice with 0.4 mg.kg(-1) B[a]P inhibited epinephrine-induced release of free fatty acids by 70%. Chronic exposure of mice to B[a]P (0.5 mg.kg(-1) injected i.p. every 48 h) for 15 days also decreased lipolytic response to epinephrine and induced a 43% higher weight gain compared with controls (B[a]P: 2.23 +/- 0.12 g versus control: 1.56 +/- 0.18 g, P < 0.01) due to increased fat mass. The weight gain occurred consistently without detectable changes in food intake. These results reveal a novel molecular mechanism of toxicity for the environmental pollutant B[a]P and introduce the notion that chronic exposure of human population to B[a]P and possibly other polycyclic aromatic hydrocarbons could have an impact on metabolic disorders, such as obesity.