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2.
Arch Pediatr ; 22(10): 1042-6, 2015 Oct.
Article in French | MEDLINE | ID: mdl-26321353

ABSTRACT

UNLABELLED: The congenital form of myotonic dystrophy type I (CDM1) corresponds to a>1500 expansion of an unstable trinucleotide (CTG) repeat. Two prognostic factors predict the risk of death in early infancy: maturity of less than 35 weeks of gestation and neonatal invasive ventilation for more than 30 days. OBSERVATION: The case of a 29-week-old premature female infant, conceived by in vitro fertilization, is reported. Generalized hypotonia led to the diagnosis of the disease. Ethical concertation about withdrawal or maintenance of intensive care was engaged, taking into account the prolonged ventilation, the degree of prematurity, and the parental wishes for maximum care. The infant was extubated after 2 months. At 17 months, motor development and precursors of language were delayed, and difficulties in feeding had required a gastrostomy. DISCUSSION: Technical advances in neonatal intensive care now allow CDM1 children to survive prolonged ventilation. The signification of such ventilatory needs on patient outcome, particularly for motor handicaps, speech and language delay, and mental deficiency, remains uncertain. The potential impact of in vitro fertilization on disease expression may also be considered. CONCLUSION: CDM1 is a severe condition, but variability in clinical manifestations and absence of genotype-phenotype correlation result in problems predicting prognosis at the individual level. Ethical issues about the level of care, notably for tracheostomy and gastrostomy, should be adapted to each case, in partnership with parents.


Subject(s)
Infant, Premature , Intensive Care, Neonatal/ethics , Myotonic Dystrophy/complications , Female , Gastrostomy , Humans , Infant, Newborn , Language Development Disorders/etiology , Motor Disorders/etiology , Positive-Pressure Respiration
3.
Food Chem Toxicol ; 84: 133-53, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26282372

ABSTRACT

Glyphosate-based herbicides (GlyBH), including Roundup, are the most widely used pesticides worldwide. Their uses have increased exponentially since their introduction on the market. Residue levels in food or water, as well as human exposures, are escalating. We have reviewed the toxic effects of GlyBH measured below regulatory limits by evaluating the published literature and regulatory reports. We reveal a coherent body of evidence indicating that GlyBH could be toxic below the regulatory lowest observed adverse effect level for chronic toxic effects. It includes teratogenic, tumorigenic and hepatorenal effects. They could be explained by endocrine disruption and oxidative stress, causing metabolic alterations, depending on dose and exposure time. Some effects were detected in the range of the recommended acceptable daily intake. Toxic effects of commercial formulations can also be explained by GlyBH adjuvants, which have their own toxicity, but also enhance glyphosate toxicity. These challenge the assumption of safety of GlyBH at the levels at which they contaminate food and the environment, albeit these levels may fall below regulatory thresholds. Neurodevelopmental, reproductive, and transgenerational effects of GlyBH must be revisited, since a growing body of knowledge suggests the predominance of endocrine disrupting mechanisms caused by environmentally relevant levels of exposure.


Subject(s)
Glycine/analogs & derivatives , Herbicides/toxicity , Pesticide Residues/toxicity , Animals , Carcinogens/analysis , Carcinogens/chemistry , Carcinogens/standards , Carcinogens/toxicity , Endocrine Disruptors/analysis , Endocrine Disruptors/chemistry , Endocrine Disruptors/standards , Endocrine Disruptors/toxicity , Glycine/analysis , Glycine/toxicity , Herbicides/analysis , Herbicides/chemistry , Herbicides/standards , Humans , Oxidative Stress/drug effects , Pesticide Residues/analysis , Pesticide Residues/chemistry , Pesticide Residues/standards , Teratogens/analysis , Teratogens/chemistry , Teratogens/standards , Teratogens/toxicity , Toxicology/methods , Glyphosate
5.
Toxicology ; 313(2-3): 122-8, 2013 Nov 16.
Article in English | MEDLINE | ID: mdl-23000283

ABSTRACT

Pesticides are always used in formulations as mixtures of an active principle with adjuvants. Glyphosate, the active ingredient of the major pesticide in the world, is an herbicide supposed to be specific on plant metabolism. Its adjuvants are generally considered as inert diluents. Since side effects for all these compounds have been claimed, we studied potential active principles for toxicity on human cells for 9 glyphosate-based formulations. For this we detailed their compositions and toxicities, and as controls we used a major adjuvant (the polyethoxylated tallowamine POE-15), glyphosate alone, and a total formulation without glyphosate. This was performed after 24h exposures on hepatic (HepG2), embryonic (HEK293) and placental (JEG3) cell lines. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. The compositions in adjuvants were analyzed by mass spectrometry. Here we demonstrate that all formulations are more toxic than glyphosate, and we separated experimentally three groups of formulations differentially toxic according to their concentrations in ethoxylated adjuvants. Among them, POE-15 clearly appears to be the most toxic principle against human cells, even if others are not excluded. It begins to be active with negative dose-dependent effects on cellular respiration and membrane integrity between 1 and 3ppm, at environmental/occupational doses. We demonstrate in addition that POE-15 induces necrosis when its first micellization process occurs, by contrast to glyphosate which is known to promote endocrine disrupting effects after entering cells. Altogether, these results challenge the establishment of guidance values such as the acceptable daily intake of glyphosate, when these are mostly based on a long term in vivo test of glyphosate alone. Since pesticides are always used with adjuvants that could change their toxicity, the necessity to assess their whole formulations as mixtures becomes obvious. This challenges the concept of active principle of pesticides for non-target species.


Subject(s)
Amines/toxicity , Ethyl Ethers/toxicity , Glycine/analogs & derivatives , Herbicides/toxicity , Polyethylene Glycols/toxicity , Surface-Active Agents/toxicity , Amines/chemistry , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Ethyl Ethers/chemistry , Glycine/chemistry , Glycine/toxicity , Herbicides/chemistry , Humans , Molecular Structure , Polyethylene Glycols/chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Surface-Active Agents/chemistry , Glyphosate
6.
J Appl Toxicol ; 33(7): 695-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-22337346

ABSTRACT

The study of combined effects of pesticides represents a challenge for toxicology. In the case of the new growing generation of genetically modified (GM) plants with stacked traits, glyphosate-based herbicides (like Roundup) residues are present in the Roundup-tolerant edible plants (especially corns) and mixed with modified Bt insecticidal toxins that are produced by the GM plants themselves. The potential side effects of these combined pesticides on human cells are investigated in this work. Here we have tested for the very first time Cry1Ab and Cry1Ac Bt toxins (10 ppb to 100 ppm) on the human embryonic kidney cell line 293, as well as their combined actions with Roundup, within 24 h, on three biomarkers of cell death: measurements of mitochondrial succinate dehydrogenase, adenylate kinase release by membrane alterations and caspase 3/7 inductions. Cry1Ab caused cell death from 100 ppm. For Cry1Ac, under such conditions, no effects were detected. The Roundup tested alone from 1 to 20 000 ppm is necrotic and apoptotic from 50 ppm, far below agricultural dilutions (50% lethal concentration 57.5 ppm). The only measured significant combined effect was that Cry1Ab and Cry1Ac reduced caspases 3/7 activations induced by Roundup; this could delay the activation of apoptosis. There was the same tendency for the other markers. In these results, we argue that modified Bt toxins are not inert on nontarget human cells, and that they can present combined side-effects with other residues of pesticides specific to GM plants.


Subject(s)
Bacterial Proteins/toxicity , Endotoxins/toxicity , Glycine/analogs & derivatives , Hemolysin Proteins/toxicity , Herbicides/toxicity , Insecticides/toxicity , Adenylate Kinase/metabolism , Apoptosis/drug effects , Bacillus thuringiensis Toxins , Biomarkers/analysis , Biomarkers/metabolism , Caspase 3/metabolism , Caspase 7/metabolism , Diet , Drug Interactions , Glycine/toxicity , HEK293 Cells , Humans , Mitochondria/metabolism , Necrosis , Pesticide Residues/analysis , Pesticide Residues/toxicity , Succinate Dehydrogenase/metabolism , Glyphosate
11.
Arch Pediatr ; 12(11): 1620-3, 2005 Nov.
Article in French | MEDLINE | ID: mdl-16185855

ABSTRACT

UNLABELLED: Meningoencephalitis due to Listeria monocytogenes is a rare and serious form of brainstem infection in childhood. OBSERVATION: We report the case of a 7 year-old girl presenting lymphocytic meningitis with a high CRP level. Parenteral antibiotics combining ceftriaxone and vancomycine led initially to clinical improvement. Ten days later, secondary brainstem inflammation with hydrocephalus appeared and led to the detection of L. monocytogenes during external ventricular bypass. CONCLUSION: This observation of paediatric lymphocytic meningoencephalitis suggests a prescription of amoxicillin in association with first line antibiotics, particularly when an important inflammatory syndrome exists, immunocompetent children included.


Subject(s)
Brain Stem/pathology , Meningitis, Listeria/etiology , Meningitis, Listeria/immunology , Anti-Bacterial Agents/therapeutic use , Brain Stem/immunology , Child , Female , Humans , Hydrocephalus/etiology , Immunocompetence , Inflammation , Meningitis, Listeria/pathology , Risk Factors
12.
J Clin Endocrinol Metab ; 90(10): 5621-6, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16030162

ABSTRACT

CONTEXT: CHARGE (coloboma, heart defect, choanal atresia, retarded growth and development, genital hypoplasia, ear abnormalities, and/or hearing loss defect) syndrome consists of a combination of congenital malformations including genital hypoplasia and retarded growth. OBJECTIVE: The objective of the study was to study gonadotropic axis function and growth parameters in CHARGE syndrome. DESIGN: This was a retrospective study. PATIENTS: The study included 32 children with CHARGE syndrome. RESULTS: Nineteen of 20 affected boys had micropenis and/or cryptorchidism, consistent with hypogonadotropic hypogonadism during fetal life. None of the boys was of pubertal age. Seven of nine boys tested before the age of 5 months during the neonatal peak period had extremely low testosterone levels. LH response to GnRH stimulation was variable during the first year of life and not correlated with existing clinical abnormalities. None of the girls over the age of 12 yr (n = 7) had begun puberty spontaneously, and a lack of response to GnRH stimulation was documented in five of them. Olfactory evaluation (n = 10) and magnetic resonance imaging (n = 18) of the forebrain revealed defective sense of smell and abnormal olfactory bulbs in all cases. Cardiorespiratory and nutritional problems were corrected, but the mean height of the 25 children who had reached 5 yr of age was -2 +/- 0.2 sd score. Height was not correlated with birth length or body mass index. GH deficiency was diagnosed in only three children. CONCLUSION: These findings suggest that CHARGE syndrome includes the main features of Kallmann syndrome, which is defined by hypogonadotropic hypogonadism combined with a defective sense of smell and abnormal olfactory bulb development. This forebrain abnormality, if confirmed in a larger group of patients, could serve as a major new criterion for the diagnosis of CHARGE syndrome.


Subject(s)
Coloboma/pathology , Gonadotropins/deficiency , Growth Disorders/pathology , Heart Defects, Congenital/pathology , Hypogonadism/pathology , Olfactory Bulb/abnormalities , Olfactory Bulb/growth & development , Body Mass Index , Child , Child, Preschool , Coloboma/metabolism , Female , Genitalia/abnormalities , Growth/physiology , Growth Disorders/congenital , Growth Disorders/metabolism , Heart Defects, Congenital/metabolism , Hormones/blood , Humans , Hypogonadism/metabolism , Hypothalamo-Hypophyseal System/growth & development , Hypothalamo-Hypophyseal System/pathology , Infant , Magnetic Resonance Imaging , Male , Nutritional Status , Olfactory Bulb/pathology , Smell/physiology , Syndrome
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